PMID- 1583488 TI - Residual efficacy of pirimiphos methyl (Actellic) on Anopheles sacharovi in Cukurova, Turkey. AB - Village-scale trials of 50% emulsifiable concentrate (EC) and 40% wettable powder (WP) formulations of pirimiphos methyl (Actellic) were carried out against Anopheles sacharovi in Cukurova, Turkey. Susceptibility tests with wild caught, gonoactive and composite aged An. sacharovi over a range of chemical concentrations resulted in 100% mortality after exposure for 60 min to a 0.5% active ingredient concentration. Surface treatments of Actellic 50% EC at 0.9 g/m2 caused a significant decrease in parous rate and a 96.9% reduction in resting density. Persistence on concrete, wood, zinc and plywood was still high at the time of the second spray round, more than 7 wk postspray and ranged from 73% (zinc) to 98% (plywood). More than 50% mortality was still recorded 8 wk postspray using 1.6 g/m2 WP on wood, plywood, zinc and thatch substrates. PMID- 1583489 TI - Larval population dynamics in a community of nearctic Aedes inhabiting a temporary vernal pool. AB - The spatial distribution and preadult mortality patterns of 4 cohabiting species of Aedes mosquitoes were studied in a temporary vernal pool at Mt. Carmel, CT, from March to May 1990. The dominant species was Ae. stimulans (79.9%), followed by Ae. canadensis (10.7%), Ae. excrucians (7.5%) and Ae. cinereus (1.9%). First instar larvae of all species aggregated at the edge of the pool and then dispersed to deeper regions as they matured. Larval mortality was high, and the majority occurred during the first stadium (80.9% for Ae. canadensis, 88.9% for Ae. excrucians, 89.1% for Ae. stimulans and 90.0% for Ae. cinereus). A predatory chaobrid, Mochlonyx cinctipes, was implicated as the major mortality factor affecting larval populations. PMID- 1583490 TI - Comparison of the synthetic pyrethroids Esbiothrin and Bioresmethrin with Scourge and Cythion against adult mosquitoes in a laboratory wind tunnel. AB - Both candidate adulticides, Esbiothrin and Bioresmethrin, exhibited quick knockdown 1-h posttreatment. Esbiothrin elicited the fastest knockdown, but Bioresmethrin was more effective at both 1- and 24-h posttreatment than either Esbiothrin or Scourge against both Aedes taeniorhynchus and Culex quinquefasciatus. Mosquitoes treated with Scourge required more time and a higher dosage to respond in a physiological manner similar to those treated with either of the candidate adulticides. More than twice the dosage rate of Cythion was required than either candidate adulticide to cause a similar physiological response in treated mosquitoes. PMID- 1583491 TI - Comparative susceptibility of species A, B and C of Anopheles quadrimaculatus complex to infection with subperiodic Brugia malayi and Brugia pahangi (Nematoda: Filarioidea). AB - Susceptibilities of natural populations of sibling species A, B and C of the Anopheles quadrimaculatus complex and the colonized strain A to subperiodic Brugia malayi and Brugia pahangi were compared. All 3 sibling species showed varying degrees of susceptibility to both B. pahangi and B. malayi, and they were considerably more susceptible to B. pahangi than to B. malayi. The rate and intensity of infection to B. pahangi were highest for species A (66.2% and 7.4 L3/female, respectively) and lowest for species B (21.3% and 1.7 L3/female). For B. malayi these values were higher for species A (29.7% and 1.84 L3/female) than for species B (13.3% and 0.86 L3/female) and C (12.6% and 0.75 L3/female). The colonized strain A of An. quadrimaculatus was significantly more susceptible to both Brugia species than the natural populations of sibling species A, B and C. PMID- 1583492 TI - Comparison of people who request mosquito control services and their non requesting neighbors. AB - The personal profiles of people who called to request mosquito control services were compared with their neighbors who did not call. Demographically, callers were generally representative of their neighbors. Callers considered the mosquito problem to be greater than did their non-calling neighbors, tended to do more things outdoors, tended to be home more, and considered themselves more attractive to mosquitoes and more allergic to mosquito bites than non-callers. There were also more newer (less than 1 year) residents among the callers than non-callers. Callers were almost exclusively from year-round-resident homeowners in long-term-resident neighborhoods. PMID- 1583493 TI - Effects of ultra-low volume and thermal fog malathion, Scourge and naled applied against caged adult Culicoides furens and Culex quinquefasciatus in open and vegetated terrain. AB - The adulticidal effect of ULV and thermal fog malathion, Scourge and naled was tested at 2x label dosage (1.42, 0.22, 0.39 oz/acre, respectively) against caged Culicoides furens and Culex quinquefasciatus in open and vegetated (orange grove) terrain. Cages were at 122 cm elevation and positioned at 15.2, 45.7, 76.2, 106.7, 137.2 and 167.6 m from the line of insecticide release. Ultra-low volume applications of all 3 insecticides were markedly more effective than thermal fog under all conditions, especially in vegetated terrain. Of the 3 insecticides, malathion performed the poorest, especially against Cx. quinquefasciatus (in which there was some resistance) and particularly when applied as thermal fog. Scourge and naled were about equally effective. The best adulticide against C. furens was naled, which was clearly superior applied as ULV. It yielded 75% mortality out to 283 m in the open, and to 38 m in the presence of dense vegetation. PMID- 1583494 TI - Efficacy of various ground-applied pyrethroids against adult Anopheles quadrimaculatus in the rice growing region of Arkansas. AB - Ground-applied ULV, cold aerosol, insecticide sprays were evaluated against caged adult female Anopheles quadrimaculatus. Treatments included 2 rates each of resmethrin, permethrin and a water-based permethrin formulation. Mortality at 24 h posttreatment was not significantly (P greater than or equal to 0.05) different between the resmethrin and water-based permethrin treatments. Both rates of permethrin were significantly (P less than 0.05) less effective than the other treatments. PMID- 1583495 TI - The killifish Rivulus marmoratus: a potential biocontrol agent for Aedes taeniorhynchus and brackish water Culex. AB - In the laboratory, newly hatched fry of Rivulus marmoratus were effective predators on 1st-instar Aedes taeniorhynchus. Adult fish consumed 4th-instar Ae. taeniorhynchus and egg rafts of Culex quinquefasciatus at a rate increasing with standard length of the fish. Predation of Rivulus marmoratus on Ae. taeniorhynchus larvae in the field was documented by observing the passage of larval/pupal remains through the gut. Laboratory reared fish released at known Ae. taeniorhynchus breeding sites survived over 1.5 years, but did not reproduce. PMID- 1583496 TI - Efficacy of permethrin- and cyphenothrin-impregnated nettings against Culex pipiens pallens. AB - Laboratory tests were conducted to determine the effect of different bed net materials, impregnated with permethrin or cyphenothrin, on Culex mosquitoes. Polyethylene, polyester and vinylon nettings were more efficacious than cotton or nylon. PMID- 1583497 TI - Isolation of mosquito-toxic bacteria from mosquito-breeding sites in Kenya. AB - A large number of source materials were collected for isolating entomopathogenic bacteria from larval mosquito habitats in Kirinyaga District, Kenya. Mosquito toxic bacteria were included among the numerous types of microorganisms isolated from the habitats. The pathogenic isolates shared common structural characteristics; they were gram-positive, spore-forming bacilli that produced parasporal inclusions conferring broad-spectrum larvicidal activity against Anopheles, Culex and Aedes mosquitoes. Based on structural and growth characteristics, coupled with larvicidal activity, the pathogenic isolates were tentatively identified as variants of Bacillus thuringiensis. Although the collection consisted of a variety of items including soil, silt and mud, the most productive materials were larval bodies. Using healthy mosquito larvae held in a fully permeable plastic bottle, a baiting technique was developed as a means of recovering bacteria from the environment. PMID- 1583498 TI - Survival of Aedes (Neomelaniconion) eggs in the laboratory. AB - Adult Aedes mcintoshi and Ae. circumluteolus were produced from eggs stored up to 9 months in the laboratory. Under standard hatching conditions, eggs stored at 24 degrees and 26 degrees C consistently produced adults for up to 9 months after collection. In contrast, eggs stored at 15 degrees C were significantly different, producing less than 1% adults from 6-12 months after collection. Aedes (Neomelaniconion) eggs can be stored and serve as a reliable source of specimens to be used in vector competence and other studies. PMID- 1583499 TI - Sulfide sensitivity in fishes of the Indian River lagoon, Florida. AB - Lagoon fishes, in netted holding cages, were placed in an impounded salt marsh and submitted to a gradient of sulfide-rich artesian well water. Near the well head, all specimens of 13 species died within 5-45 min, while all individuals of 5 species survived. More distant from the well, survival time increased sufficiently to rank species in approximate order of sensitivity to sulfide. PMID- 1583500 TI - Evaluation of three candidate cypermethrin-piperonyl butoxide formulations compared with Scourge against adult Culex quinquefasciatus. AB - Cypermethrin-piperonyl butoxide formulations (1:1, 1:5, 1:10) were evaluated in a laboratory wind tunnel against colony reared, susceptible adult Culex quinquefasciatus mosquitoes. Scourge (4% resmethrin:12% piperonyl butoxide) was used as the standard for comparison. Based on the LC90 data, the 3 cypermethrin piperonyl butoxide formulations were 2.6-3.7x more toxic than Scourge 24-h posttreatment. PMID- 1583501 TI - Susceptibility of Phlebotomus papatasi (Diptera: Psychodidae) to DDT in some foci of cutaneous leishmaniasis in Iran. AB - The susceptibility of Phlebotomus papatasi to DDT was studied in field surveys at localities in different areas of Iran during 1985-88. In many parts of Iran houses had been treated with DDT for malaria control (1950-68). Tests were carried out in localities where the application of DDT had been discontinued since 1969. This investigation showed that P. papatasi from Isfahan is more tolerant to DDT than flies from other areas, probably a manifestation of DDT resistance. PMID- 1583502 TI - Electrophysiologic findings in post-traumatic syringomyelia: implications for clinical management. AB - Traumatic spinal cord injured (SCI) patients may develop pain, new weakness and/or sensory loss due to an enlarging fluid-filled cyst in the spinal cord. The clinical history and physical exam are nonspecific and insensitive, particularly for diagnosing and monitoring recurrent or progressive post-traumatic syringomyelia (PTS). We compare the sensitivity and specificity of three electrodiagnostic tests, median and ulnar F waves, electromagnetic motor evoked potentials (MEP), and needle electromyography, with respect to syrinx by imaging (MRI or CT scan) and neurologic progression on serial clinical exams. Central motor conduction time (CMCT) calculated from scalp and spine MEP was the most sensitive diagnostic test. F waves were less sensitive and less specific than the CMCT, and did not provide evidence of syrinxes in the mid or upper cervical cord. Positive sharp wave and fibrillation potentials were the least sensitive and least specific. The CMCT is a useful adjunct to imaging studies for diagnosing and monitoring PTS. PMID- 1583503 TI - Fertility of spinal cord injured males: effect of genitourinary infection and bladder management on results of electroejaculation. AB - Thirty-eight men undergoing electroejaculation (EEJ) procedures for anejaculatory infertility were examined for the presence or absence of infection in urine and semen. In 29 spinal cord injury patients, a high incidence of infected urine and infected semen (41% and 56%, respectively) was seen, in contrast to patients with normal bladder function (0% and 11%). Urinary infection was associated with slightly lower sperm quality and lower pregnancy rates (10% vs 30% in the presence of sterile urine). Semen infection had no effect on sperm counts or pregnancy rates. If intermittent self-catheterization (ISC) was used to empty the neurogenic bladder, slightly better sperm quality was seen, the total failure rate was less, and much better pregnancy rates (44%) resulted than for patients using an alternative bladder management (7%). Antibiotics did not reduce the incidence of urine or semen infection, but did improve sperm counts slightly. Continuous prophylaxis was associated with bacterial resistance to many oral antibiotics and had no advantage over a short course of antibiotics prior to the procedure. Despite the above associations, the sperm quality in our patient population was never normal compared with that of men who ejaculate normally. We conclude that the low sperm quality seen in electroejaculation specimens from spinal cord injured males is not due entirely to infection or to the type of bladder management. Short courses of antibiotics, instead of continuous antibiotic prophylaxis, may be beneficial. Intermittent catheterization is superior to other methods of neurogenic bladder management in maintaining the fertility of spinal cord injured men. PMID- 1583504 TI - Perceptual deprivation in the acute phase of spinal injury rehabilitation. AB - Patients in intensive care units are often reported to experience psychological disturbances which may be attributable to a number of well-researched causes. However, it is suggested that the total lack of proprioceptive and motor feedback after spinal trauma may be a significant factor in the genesis of these disturbances which are unique to this group of patients. All cases admitted to the Regional Spinal Injuries Centre in Southport from January 1987 through December 1990 were assessed (n = 187) and the conditions surrounding the occurrence of behavioural disturbances (n = 23, 12.3%) established. The level of interaction with relatives and significant others was established for all acute admissions, and low frequency was found to correlate significantly with the development of perceptual deprivation experiences. The effects of inadequate somatosensory input, lesion level, increasing age, and visitor variability for spinal patients is discussed and an algorithm presented to highlight the potential factors associated with aetiology and treatment of the problem. The implications of these findings for the future management of acute spinal trauma are discussed. PMID- 1583505 TI - Seasonal affective disorder in a spinal cord injury population. AB - Seasonal Affective Disorder (SAD) has received formal research attention only within the last eight years. Diagnostic criteria for SAD include many characteristics typical of depression: sadness, low self-esteem, lack of energy, social withdrawal, and suicide ideation, and features of atypical depression: carbohydrate craving, overeating, weight gain, and hypersomnia. Differential diagnosis of the disorder depends on an onset in fall/winter and remission in spring/summer. It was hypothesized that spinal cord injury (SCI) patients would have a higher incidence of the disorder in the northern latitudes because of decreased outdoor activities in winter and because of such light-depriving winter survival tactics as installing opaque plastic for storm windows. SCI patient responded to a postal survey which included Rosenthal's Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI). Results showed a substantially higher rate of SAD among SCI patients than in the normative sample. PMID- 1583506 TI - American Spinal Injury Association annual meeting. Toronto, Canada, 8-10 May 1992. Abstracts. PMID- 1583507 TI - Antoni van Leeuwenhoek 1632-1723. PMID- 1583508 TI - Cysticercosis and cerebrovascular disease: a review. AB - Ischaemic cerebrovascular disease is a relatively common but under-recognised complication of neurocysticercosis. It is usually caused by inflammatory occlusion of the arteries at the base of the brain secondary to cysticercotic arachnoiditis. In most cases, the involved vessels are of small diameter and the neurological picture is limited to a lacunar syndrome secondary to a small cerebral infarct. However, large infarcts related to the occlusion of the middle cerebral artery or even the internal carotid artery have also been reported in this setting. CT and CSF examination usually support the cause-and-effect relationship between neurocysticercosis and the cerebral infarct by showing abnormalities compatible with cysticercotic arachnoiditis. An accurate diagnosis of this condition is important since early treatment with steroids is advised to ameliorate the subarachnoid inflammatory reaction which may cause recurrent cerebral infarcts. PMID- 1583509 TI - Serial MRI and neurobehavioural findings after mild to moderate closed head injury. AB - Fifty patients who sustained mild to moderate closed head injury (CHI) underwent a CT scan, MRI, and neurobehavioural testing. At baseline 40 patients had intracranial hyperintensities detected by MRI which predominated in the frontal and temporal regions, whereas 10 patients had lesions detected by CT. Neurobehavioural data obtained during the first admission to hospital disclosed no distinctive pattern in subgroups of patients characterised by lesions confined to the frontal, temporal, or frontotemporal regions, whereas all three groups exhibited pervasive deficits in relation to normal control subjects. The size of extraparenchymal lesion was significantly related to the initial Glasgow Coma Scale score, whereas this relation was not present in parenchymal lesions. One and three month follow up MRI findings showed substantial resolution of lesion while neuropsychological data reflected impressive recovery. The follow up data disclosed a trend from pervasive deficits to more specific impairments which were inconsistently related to the site of brain lesion. These results corroborate and extend previous findings, indicating that intracranial lesions detected by MRI are present in most patients hospitalised after mild to moderate CHI. Individual differences in the relation between site of lesion and the pattern of neuropsychological findings, which persist over one to three months after mild to moderate CHI, remain unexplained. PMID- 1583510 TI - Stroke topography and outcome in relation to hyperglycaemia and diabetes. AB - In a prospective study to analyse stroke topography and outcome in diabetics and to determine the prognostic value of blood glucose and glycosylated haemoglobin estimation, we evaluated 176 patients with acute stroke. The patients were classified into four groups on the basis of history, fasting glucose, and glycosylated haemoglobin: euglycaemic patients with no history of diabetes, stress hyperglycaemia, newly diagnosed diabetics, and known diabetics. A high prevalence of undiagnosed diabetes was shown. No difference was found in the type or site of stroke between the four groups. No difference was found in the site of symptomatic or incidental lesions on computerised axial tomography. Patients with stress hyperglycaemia and known diabetics had more severe strokes. Mortality was higher in patients with stress hyperglycaemia, newly diagnosed diabetics, and the combined diabetes groups. This increased mortality was evident in the hyperglycaemic and diabetic groups, even after excluding patients with cerebral haemorrhage. Stroke severity and mortality also increased independently with blood glucose in the euglycaemic group. We conclude that there is a correlation between admission glucose concentration, diabetes, and poor stroke outcome, which may not be attributed to stroke type or location. PMID- 1583511 TI - Development of prognostic index for primary supratentorial intracerebral tumours. AB - The clinical course of intrinsic supratentorial tumours is variable. Prediction of outcome would be useful in defining patients for specific treatment policies. A retrospective analysis of 560 patients with intrinsic supratentorial tumours was performed. Proportional hazards models for survival were derived by using a stepwise selection procedure with only clinical and CT features as possible explanatory variables. The variables of prognostic importance were age, a first symptom of epilepsy, focal signs at presentation, a cystic lesion on CT scan, and duration of symptoms before presentation. The model defined a group with a good prognosis (score less than or equal to 9, n = 211) and a group with a poor prognosis (score greater than 9, n = 344). The median survival was 27 months for those with a score less than or equal to 9 or less and three months for those with score greater than 9. An alternative model, not including duration of symptoms, is also capable of defining groups with long (score less than or equal to 16, n = 234) and short (score greater than 16, n = 325) survival. The model may provide a means of classifying patients for inclusion in prospective randomised studies. PMID- 1583512 TI - Mechanisms of pain relief by vibration and movement. AB - Mechanisms of pain relief induced by vibration and movement were investigated. A CO2 laser beam, which is useful for pure nociceptive stimulation, was used for recording pain-related somatosensory evoked potentials (pain SEPs) and for measuring pain threshold and reaction time (RT). Concurrently applied vibratory stimuli to and active movements of the fingers significantly reduced and prolonged pain SEPs, increased pain threshold, and prolonged RT, indicating that an increase in the inhibitory mechanisms of painful feeling was induced by the concurrently adopted sensory inputs mediated by large myelinated fibres. In contrast, continuous cooling enhanced pain SEPs and decreased pain threshold, probably due to the spatial summation of two kinds of nociceptive impulses mediated by the same pathways. The results of this investigation throw light on the mechanisms of the alleviation of pain by vibration and movement. PMID- 1583513 TI - CSF hydrodynamics in superior sagittal sinus thrombosis. AB - Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion method in patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations up to 15 years after the onset of the disease. A total of 70 CSF hydrodynamic examinations were performed. A clear increase in intracranial pressure due to raised pressure in the major dural sinus was seen in all patients. A striking feature was the persistent intracranial pressure increase that declined only gradually. This had no obvious clinical impact. Change in CSF resorption facility played only a minor role in the intracranial pressure elevation. None of the patients developed hydrocephalus. PMID- 1583514 TI - Transcranial magnetic stimulation in pontine infarction: correlation to degree of paresis. AB - Transcranial magnetic stimulation was performed in 20 patients with pontine infarction who had initially some degree of hemiparesis. Only patients with a well defined lesion on magnetic resonance imaging that was appropriate for the neurological signs were included. Recordings were made from the abductor pollicis brevis muscle (APB) bilaterally. The degree of hand paresis was estimated clinically and related to the following parameters: central motor conduction time (CMCT), interside latency difference of total latency, and amplitude ratio of affected to unaffected side. Increasing degree of paresis was associated with increasing latency parameters and decreasing amplitude ratio. In the four patients with severe paresis a low amplitude response could be evoked and CMCT was delayed by up to 10 ms. When the paresis had resolved at the time of transcranial magnetic stimulation CMCT was normal. However, amplitude ratio was less than 100% in all but one patient, with most of the values ranging between 40% and 60%, which indicates a subclinical pyramidal tract lesion. Median nerve sensory evoked potentials (SEP) and related interside latency difference to amplitude ratio N20/P25 were also recorded. In contrast to TCMS, decreased amplitude ratio of SEP was not associated with delayed latency. Clinically, the mild degree of and good recovery from paresis in ventral pontine infarction was remarkable. PMID- 1583515 TI - Meningeal sarcoidosis, pseudo-meningioma, and pachymeningitis of the convexity. AB - Two cases of meningeal sarcoidosis with unusual and misleading presentations are reported. In the first case, CT scan, angiographic, and MRI findings were indistinguishable from those of meningioma. CSF pleiocytosis may help in diagnosing sarcoid pseudo-meningioma. The second patient had transient focal deficits and pachymeningitis of the convexity. The transient deficits were probably of epileptic origin based on their response to antiepileptic treatment. The diagnosis of neurosarcoidosis was made only after meningeal biopsy, despite thorough investigations. PMID- 1583516 TI - Platelet catecholamines in cluster headache. AB - Platelet tyrosine and catecholamine (CA) content was measured in cluster headache sufferers during the different phases of the illness. Compared with controls, cluster headache sufferers had lower platelet levels of norepinephrine (NE) and epinephrine (E) in all phases of the syndrome. Tyrosine levels were increased significantly during the cluster headache attack. We suggest that these results provide biochemical evidence of sympathetic nervous system (SNS) hypofunction in cluster headache. PMID- 1583517 TI - The role of radiation therapy in the management of spinal cord compression due to extramedullary haematopoiesis in thalassaemia. AB - Extramedullary haematopoiesis associated with thalassaemia leading to spinal cord compression is an extremely rare event in the course of the disease. The efficacy of radiation therapy is advocated in the management of such a complication. Two patients with thalassaemia, who had presented with spinal cord compression, were successfully treated by a modest dose of local radiotherapy. In one of the patients, however, radiotherapy was resorted to after an initial decompressive laminectomy and partial removal of the intraspinal haematopoietic mass proved unsuccessful. The other patient was managed solely by radiation therapy. PMID- 1583518 TI - Temporally related changes of sleep complaints in traumatic brain injured patients. AB - Sleep complaints were obtained from 22 hospitalised patients with traumatic brain injury of recent onset (median 3.5 months after injury) and were compared with those of 77 discharged patients who had sustained brain injury about two to three years (median 29.5 months) previously. A high incidence of sleep complaints was noted in both groups (72.7% and 51.9% respectively). Disorders in initiating and maintaining sleep (DIMS) were the most common complaints among hospitalised patients (81.2%), whereas disorders of excessive somnolence (DOES) were common in discharged patients (72.5%). This difference in the nature of the complaints was apparently due to differences between the two groups in the time elapsed since injury, duration of coma, and immediate environmental conditions. In discharged patients with sleep complaints, neurobehavioural impairments and a poorer occupational outcome were more common than in those discharged patients without sleep complaints. It is suggested that early evaluation and treatment of sleep disturbances must be considered an integral part of the rehabilitation process. PMID- 1583519 TI - Unilateral diaphragmatic paralysis: an electrophysiological study. AB - An electrophysiological study was carried out on four patients with unilateral diaphragmatic paralysis. Whereas neurogenic involvement of the paralysed hemidiaphragm was roughly similar in all cases, neurogenic patterns could be detected in the normally moving contralateral hemidiaphragm in three cases, and the degree of involvement could be correlated with the respiratory state of the patients. EMG also showed that the neuropathic process affected the limb muscles. Thus unilateral diaphragmatic paralysis may be, at least in some cases, the localised expression of a more diffuse neuropathy, perhaps a peculiar form of neuralgic amyotrophy. PMID- 1583520 TI - Subcortical aphasia from a thalamic abscess. AB - A patient is reported who was treated successfully for a left thalamic abscess that resulted in subcortical aphasia. A SPECT scan showed large areas of hypoperfusion in the cortex of the left hemisphere. At follow up after seven months there was marked improvement in the language disorder and the cortical hypoperfusion. It is suggested that aphasia in patients with subcortical lesions results from secondary cortical dysfunctions. The evidence is confined to patients with stroke lesions. The possible implications of this case on current theories of pathophysiological mechanisms, in particular the ischaemic penumbra theory and the cortical diaschisis theory, are briefly discussed. Cortical diaschisis may be the appropriate explanation in this patient. PMID- 1583521 TI - Familial hypokalaemic periodic paralysis in Finland. AB - Seven families with familial hypokalaemic periodic paralysis were found in Finland. Nine of the 103 asymptomatic family members studied had abnormal results on a potassium exercise test. The overall prevalence of familial hypokalaemic periodic paralysis in Finland was 0.4/100,000. Carbohydrate intake and hard exercise were the most important triggers of paralytic attacks. Half of the patients reported having attacks at least once a month. Seven patients reported cardiac symptoms (especially bradycardia) during attacks. Permanent muscular weakness was not prominent. PMID- 1583522 TI - Middle cerebral artery pulsatility in children with blocked cerebrospinal fluid shunts. AB - The application of transcranial Doppler ultrasound to the diagnosis of blocked ventriculo-peritoneal shunts was studied in 63 children. Thirty two of these required shunt revision, whereas in 31 children symptoms resolved without surgery. The group of children requiring shunt revision had a significantly higher mean Gosling pulsatility index, than both the group of children whose symptoms resolved and a group of age-matched controls (p less than 0.001). Those with a raised pulsatility index were more likely to have higher intracranial pressure. There was no correlation between CT scan changes and the pulsatility index. PMID- 1583523 TI - Intramuscular midazolam for treatment of acute seizures or behavioral episodes in patients with brain injuries. PMID- 1583524 TI - HLA profile and HTLV-I associated myelopathy (HAM/TSP) in Natal, South Africa. PMID- 1583525 TI - Extrapyramidal symptoms in a patient treated with fluvoxamine. PMID- 1583526 TI - Clinical onset and MRI features of Krabbe's disease in adolescence. PMID- 1583527 TI - Mental representation and temporary recovery from unilateral neglect after vestibular stimulation. PMID- 1583528 TI - Ceftazidime encephalopathy: absence status and toxic hallucinations. PMID- 1583529 TI - Diurnal variations of whole blood serotonin content in patients with depression and neurosis. PMID- 1583530 TI - Cerebrospinal fluid (CSF) cytology: current status and diagnostic applications. AB - Cytologic evaluation of cerebrospinal fluid (CSF) is an effective means for diagnosing many disorders involving the central nervous system (CNS). Interpretation of these samples requires an understanding of the spectrum of neurologic diseases which involves the subarachnoid space, either primarily or secondarily, as well as familiarity with the cytologic characteristics of these lesions. Here the clinical features and cytologic presentation of common conditions which can be diagnosed by CSF cytology are reviewed. Preparatory methods for CSF examination are discussed and normal and reactive conditions involving CSF, lymphoma, leukemia, meningeal carcinomatosis and the subarachnoid spread of primary brain tumors are described and illustrated. PMID- 1583531 TI - Bone marrow-derived elements in the central nervous system: an immunohistochemical and ultrastructural survey of rat chimeras. AB - This report defines the bone marrow-derived elements found in the central nervous system of adult rat radiation chimeras. Four cell types were identified which bore the major histocompatibility (MHC) class I molecules of the donor rat strain thereby indicating a marrow origin. They were: meningeal macrophages, perivascular "microglial" cells, lymphocytes and rare cells with parenchymal microglial morphology. These cells were examined by immunohistochemical methods at the light microscopic and ultrastructural levels. Extended descriptions of the perivascular marrow-derived elements and the parenchymal microglial cells are presented. These latter two cell types, which exist in humans, have a significant role in neuroimmune processes and most probably function as the antigen presenting cells in the central nervous system of mammals. PMID- 1583532 TI - Expression of major histocompatibility complex antigens in the brains of patients with progressive multifocal leukoencephalopathy. AB - Progressive multifocal leukoencephalopathy (PML) is caused by JC virus (JCV) infection of the central nervous system (CNS) in immunosuppressed patients. The immunopathogenesis of this chronic encephalitis is unknown. Because major histocompatibility (MHC) class I and class II antigens are important in modulating the immune response and viral clearance, we examined the tissue expression of MHC molecules in relation to CNS damage and presence of virus. By immunocytochemical staining, both MHC class I and class II antigens were expressed at high levels within PML lesions. Beta-2 microglobulin (beta-2m) was present on endothelial cells and JCV-infected oligodendroglia within the lesions. Also, many astrocytes with bizarre morphology expressed MHC class I antigens. In histologically normal regions of PML brains expression of beta-2m was noted only on endothelial cells. Expression of MHC class II also was focused within demyelinating lesions and was restricted to macrophages/microglia and occasional endothelial cells. When compared to other viral encephalitides (e.g. human immunodeficiency virus) these findings suggest that intra-CNS immune response to JCV is appropriate for antigenic presentation; however, the absence of responsive systemic T-cells may lead to chronic viral infection with progressive neuropathology. PMID- 1583533 TI - Ultrastructural characterization of cerebellar diffuse plaques in Alzheimer's disease. AB - We examined the ultrastructural localization of beta/A4 protein in cerebellar diffuse plaques (DP) in three Alzheimer's disease brains by the indirect immunoperoxidase technique. Intense immunoreaction products were scattered in the DP; they were strongly suggested to be located between small cell processes. Reaction products were dot-like and/or amorphous, and occasionally fibrillar. Adjacent semithin sections of regions immunoreactive for beta/A4 protein revealed only very small amounts of amyloid fibrils between cell processes and/or small numbers of degenerating neurites. The small degenerating neurites which appeared in most DP lacked paired helical filaments (PHF) and neurofilaments (NF). These findings suggest that the majority of the beta/A4-immunoreactive substance in cerebellar DP is non-fibrillar pre-amyloid found between cell processes and barely detectable by routine electron microscopy. PMID- 1583534 TI - An antibody against hyperphosphorylated neurofilament proteins collapses the neurofilament network in motor neurons but not in dorsal root ganglion cells. AB - The carboxyl-terminal region of both the medium and high molecular weight neurofilament proteins contains repeated sequences that are sites for phosphorylation. The monoclonal antibody SMI31 specifically recognizes the conformation of these multiphosphorylated domains in an intermediate state of phosphorylation. Microinjection of SMI31 into living spinal motor neurons in culture resulted in a gradual collapse of the arrays of neurofilaments in perikarya and dendrites. In some cells, antibody-decorated filaments penetrated the axon and accumulated in proximal axonal segments causing their swelling. In dorsal root ganglion neurons, microinjected SMI31 bound to neurofilaments but did not induce collapse of the network or proximal axonal swelling. This study supports a role for phosphorylation of neurofilament sidearms in control of neurofilament transport and illustrates that interference with these sites has different consequences on neurofilament organization and morphology in different cell types. PMID- 1583535 TI - Ultrastructural location of major histocompatibility complex (MHC) class II positive perivascular cells in histologically normal human brain. AB - The expression of major histocompatibility complex (MHC) class I and II antigens was studied in surgical and postmortem brain biopsy tissue using light and electron microscopic immunocytochemistry. In addition, monoclonal antibodies directed against human macrophages (EBM11) and alpha-smooth muscle actin were applied. It is shown that blood vessel-associated MHC class II immunoreactivity in histologically normal human brain can be localized to a distinct class of cells, termed perivascular cells, which share macrophage but not smooth muscle cell antigen. This immunophenotype, the location in the perivascular space as well as the morphology, frequency and tissue distribution distinguish perivascular cells from pericytes and intraparenchymal microglia. It is suggested that MHC class II positive perivascular cells are a normal constituent of the human cerebral microvasculature. The potential role of these cells in immunological reactions occurring at the blood-brain interface is discussed. PMID- 1583536 TI - A prediction of the three-dimensional structure of maize NADP(+)-dependent malate dehydrogenase which explains aspects of light-dependent regulation unique to plant enzymes. AB - A model has been built for the plant NADP-malate dehydrogenase from Zea mays, a key enzyme in photosynthesis, which undergoes light-dependent regulation. The model was based on sequence and presumed structural homology to the known three dimensional structure of mammalian porcine cytosolic NAD-malate dehydrogenase. A cystine-loop present in an extended C-terminal region of plant NADP-malate dehydrogenases was modelled using molecular mechanics and computer graphical methods, based on the assumption that a disulphide bridge exists in the inactive form of the enzyme between Cys351 and Cys363. The predicted conformation of the intact C-terminal cystine-loop suggests that the extended polypeptide will bind in the active centre and inhibit enzyme activity. Another ionizable cysteine residue in the active site is predicted to control the charge of the catalytic His215 and might be responsible for the uniquely tight binding of the positively charged nicotinamide ring of NADP+ in this and other C4 and C3 plant NADP-malate dehydrogenases. PMID- 1583537 TI - Models for the binding of amiodarone to the thyroid hormone receptor. AB - The antiarrhythmic drug amiodarone has recently been characterized as the first known thyroid hormone antagonist. Its mode of interaction with the thyroid hormone receptor is therefore of interest. A computational analysis of the conformational flexibility of amiodarone using molecular mechanics and the semiempirical molecular orbital method AM1 has been performed. The molecular mechanics studies show that the low-energy conformations of the benzoylbenzofuran portion of amiodarone can be grouped into 4 distinct classes, while the diethylaminoethoxy side chain is extremely flexible. Conformers representative of the 4 low-energy classes were fitted to an extended thyroid hormone receptor model. Four independent modes in which amiodarone could bind to the thyroid hormone receptor site were evaluated. PMID- 1583538 TI - Computer-aided molecular modeling and design of DNA-inserting molecules. AB - Intercalators are molecules capable of sliding between base pairs without disturbing the overall stacking pattern. In addition, there may exist molecules capable of inserting into a base pair thereby disrupting the hydrogen bonds and replacing them with new hydrogen bonds. A molecule probably capable of inserting, i.e., an insertor, is the diketopiperazine cyclo-[Gly-Gly] (1). A barbiturate (2), alloxan (3), a pyrimidine derivative (4) and a hydantoin (5) were also studied as possible insertors. Furthermore, molecules such as ethyleneurea (6), succinimide (7), as well as a malonamide derivative (8) and oxamide derivatives (9-11) were studied in order to investigate the arrangement and the number of hydrogen bonds necessary for insertion. Molecules 12-14 were designed and studied for their capacity to act as bisinsertors and/or bisintercalators. These molecules feature two diketopiperazine moieties which are connected via a diphenyl(thio)ether, i.e., 12 and 13, or a bisphenol A spacer, i.e., 14. The latter molecule (14) seems a promising candidate as a bisinsertor. PMID- 1583539 TI - Pharmacophore identification by molecular modeling and chemometrics: the case of HMG-CoA reductase inhibitors. AB - A methodology based on molecular modeling and chemometrics is applied to identify the geometrical pharmacophore and the stereoelectronic requirements for the activity in a series of inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme involved in cholesterol biosynthesis. These inhibitors present two common structural features - a 3,5-dihydroxy hepatanoic acid which mimics the active portion of the natural substrate HMG-CoA and a lipophilic region which carries both polar and bulky groups. A total of 432 minimum energy conformations of 11 homologous compounds showing different levels of biological activity are calculated by the molecular mechanics MM2 method. Five atoms are selected as representatives of the relevant fragments of these compounds and three interatomic distances, selected among 10 by means of a Principal Component Analysis (PCA), are used to describe the three-dimensional disposition of these atoms. A cluster analysis procedure, performed on the whole set of conformations described by these three distances, allows the selection of one cluster whose centroid represents a geometrical model for the HMG-CoA reductase pharmacophore and the conformations included are candidates as binding conformations. To obtain a refinement of the geometrical model and to have a better insight into the requirements for the activity of these inhibitors, the Molecular Electrostatic Potential (MEP) distributions are determined by the MNDO semiempirical method. PMID- 1583540 TI - The computer program LUDI: a new method for the de novo design of enzyme inhibitors. AB - A new computer program is described, which positions small molecules into clefts of protein structures (e.g. an active site of an enzyme) in such a way that hydrogen bonds can be formed with the enzyme and hydrophobic pockets are filled with hydrophobic groups. The program works in three steps. First it calculates interaction sites, which are discrete positions in space suitable to form hydrogen bonds or to fill a hydrophobic pocket. The interaction sites are derived from distributions of nonbonded contacts generated by a search through the Cambridge Structural Database. An alternative route to generate the interaction sites is the use of rules. The second step is the fit of molecular fragments onto the interaction sites. Currently we use a library of 600 fragments for the fitting. The final step in the present program is the connection of some or all of the fitted fragments to a single molecule. This is done by bridge fragments. Applications are presented for the crystal packing of benzoic acid and the enzymes dihydrofolate reductase and trypsin. PMID- 1583541 TI - Computer simulation of the conformational behaviour of angiotensinogen (6-13) renin substrate. AB - The conformational behaviour of the biologically active angiotensinogen (6-13) fragment has been investigated by computer simulations. A large sample of conformers has been generated using the Monte-Carlo procedure, then analysed using classification and partition methods. Seven families can describe the conformational distribution. About 40% of conformers are fully extended, 28% are folded at the C-terminal His6-Pro7-Phe8-His9 level and the others are folded at different levels. The study highlights the extreme flexibility of the angiotensinogen fragment. PMID- 1583542 TI - Watching our numbers double. PMID- 1583543 TI - Capnographic trend curve monitoring can detect 1-ml pulmonary emboli in humans. AB - To evaluate the potential of trend monitoring of end-tidal PCO2 (PETCO2) to detect pulmonary embolization, the capnograms of 24 mechanically ventilated patients were monitored during simulation of 1-ml pulmonary embolization by inflation of the balloons of their pulmonary artery catheters. Within 1 minute of balloon inflation, PETCO2 showed an exponential decrease to a new equilibrium. This response is characteristic of a CO2 wash-out curve produced by a step increase in dead space. Because of a steady baseline, the depression of the trend line during balloon inflation was apparent to a naive reader repeatedly in 20 of the 24 patients (sensitivity, 85%; specificity, 94%; positive predictive value, 98%; negative predictive value, 89%), despite a small mean decrease in PETCO2 (2 +/- 1.97 mm Hg). The PETCO2 trend curve did not reliably allow detection of balloon inflation in 4 patients whose capnograms were poorly formed. In conclusion, during constant ventilation, PETCO2 trend curve monitoring might provide clinically useful "on line" information regarding pulmonary embolization. PMID- 1583544 TI - The susceptibility of thermistor-based esophageal temperature probes to errors caused by electrically conductive fluids ("artificial saliva"). AB - Several brands of esophageal stethoscopes with thermistor-based thermometers were tested to determine the susceptibility of the probe connector to contamination by oral secretions. A solution of half normal saline and 1% carboxy-methyl-cellulose was used to model the conductivity and viscosity of saliva. When 1 ml of test solution was allowed to track down the probe wires to the connector, several brands of thermistors gave erroneously elevated readings. The mean changes in temperature according to brand of thermistor were as follows: Electromedics, 0.1 +/- 0.1 degree C; Mallinckrodt, 1.7 +/- 0.8 degrees C; Respiratory Products, 0.1 +/- 0.2 degrees C; Sheridan, 3.6 +/- 1.9 degrees C; Vital Signs, 4.8 +/- 1.3 degrees C (peak) and 1.4 +/- 1.6 degrees C (final); and Yellow Springs, 0.9 +/- 0.4 degrees C. The manufacturers of the probes susceptible to this type of error should implement the appropriate design modifications. In the meantime, clinicians should be aware of this problem and may choose to prevent these errors by wrapping the connection with waterproof tape. PMID- 1583545 TI - Variability of blood gases, pulse oximeter saturation, and end-tidal carbon dioxide pressure in stable, mechanically ventilated trauma patients. AB - We evaluated the short-term variability of PaO2, PaCO2, pulse oximeter saturation (SpO2), and end-tidal PCO2 (PETCO2) in mechanically ventilated trauma patients. All patients were stable and undisturbed during the evaluation periods. Blood gases were obtained from an arterial catheter 4 times at 20-minute intervals. SpO2 and PETCO2 were recorded when the blood gases were obtained. Fifty evaluations were made in 26 patients; 24 patients were evaluated twice, with greater than or equal to 24 hours between evaluation periods. Variability was expressed as coefficient of variation (%CV) for each evaluation period. The median %CVs were 3.6% for PaO2 (95th percentile = 9.8%), 0.5% for SpO2 (95th percentile = 1.4%), 2.8% for PaCO2 (95th percentile = 7.4%), and 2.4% for PETCO2 (95th percentile = 7.1%). The overall correlation between PaCO2 and PETCO2 was r = 0.80, and the mean difference between PaCO2 and PETCO2 was 0.9 +/- 3.6 mm Hg. The variability of PETCO2 was similar to the variability of PaCO2. However, the variability of PaO2 was considerably greater than that of SpO2, which was probably related to the shape of the oxyhemoglobin dissociation curve and the relatively high saturations of the patients in this study. Variability of blood gases, SpO2, and PETCO2 should be considered when these values are clinically interpreted. PMID- 1583546 TI - Comparative analysis between epidural (Gaeltec) and subdural (Camino) intracranial pressure probes. AB - The new fiberoptic Camino system has recently been introduced for clinical intracranial pressure (ICP) monitoring. We compared the subdural Camino system with the well-established epidural Gaeltec system in both in vitro and clinical conditions. In the in vitro experiments the intracranial vault was simulated by a tightly closed, fluid-filled box (0.9% sodium chloride) with the two probes inside. We simulated pulsating waveforms with a jet ventilator. No difference between the simulated curve patterns and values could be detected. In the clinical studies, both probes were implanted in 10 patients who had either head injuries, subarachnoid hemorrhage, or intracerebral hemorrhage. The in vivo comparison revealed no significant difference between the two systems in the recorded pressures in group 1 (ICP less than 20 mm Hg). The subdurally placed Camino probe showed insignificantly lower ICP values than did the extradural Gaeltec probe. Although group 2 (ICP greater than 20 mm Hg) waveforms were nearly identical, significant differences (p less than 0.01) in pressure measurements (systolic, diastolic, and mean) occurred (Camino, 18 +/- 3 mm Hg; Gaeltec, 27 +/- 3 mm Hg). Correlation coefficients for mean ICP values were 0.82 in group 1 and 0.49 in group 2. Problems with the Camino probe were usually mechanical and occurred in 2 patients. The problems were either easy to recognize or manifested as an ostensibly pathologic curve. No infection occurred with either system during or following implantation. The dissimilar characteristics of the two probes can be ascribed to their different extradural and subdural implantation sites. The Gaeltec probe was more durable over the period of implantation, which averaged 98 hours and ranged from 44 to 298 hours.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583547 TI - Pressure monitoring can accurately position catheters for air embolism aspiration. AB - Venous air embolism is a potentially catastrophic surgical complication. While prevention and early diagnosis represent the cornerstones of management, definitive therapy of a massive air embolus relies on aspiration of the air through an appropriately located multiorifice catheter. Currently, the most common method for accurately positioning a multiorifice catheter in the high right atrium is an intravenous electrocardiogram (IVECG). Because that method is not always technically feasible, we evaluated a right ventricular waveform as a marker for accurate and reliable catheter localization. Twenty patients were prospectively evaluated. After successful insertion of an antecubital introducer sheath, a multiorifice catheter was advanced into the central circulation (5 orifices, one at the distal tip and four 1.0 x 1.5 mm side orifices spaced 0.5 cm apart beginning 1.2 cm from the distal tip). Simultaneous IVECG and pressure waveforms were monitored. After the catheter was advanced into the right ventricle, it was withdrawn until an IVECG P-wave characteristic of the superior vena cava-right atrial junction was observed. The time from cannulation of the basilic vein until obtaining a characteristic IVECG of the superior vena cava right atrial junction was 6.6 +/- 4.2 minutes (mean +/- SD). The distance between loss of the right ventricular waveform to the appearance of the desired IVECG P wave configuration was 3.6 +/- 0.35 cm (mean +/- SD). Because the origin of the observed IVECG complex (1.7 cm proximal to the distal orifice) and of the right ventricular waveform are located in two different places, the tip of the catheter was not considered to be in an optimal position for air aspiration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583548 TI - Effects of hypocapnia on canine spinal, subcortical, and cortical somatosensory evoked potentials during isoflurane anesthesia. AB - Although hyperventilation with hypocapnia is frequently used in the management of neurosurgical patients in whom sensory-evoked potentials may be monitored, the effects of hypocapnia on evoked potentials have not been described with precision. In the present experiment, the effects of randomized arterial carbon dioxide tensions of 20, 25, 30, and 35 mm Hg on spinal, subcortical, and cortical somatosensory-evoked potentials (SEPs) were measured in dogs anesthetized with 1.40% isoflurane. Other variables known to affect the SEP (temperature, blood pressure, and arterial oxygen tension) were stable throughout the experiment. Hypocapnia caused reductions in the latencies of the early peaks of the spinal and subcortical SEPs. These differences were small, consisting of a 2% shortening of latency at 20 mm Hg carbon dioxide tension when compared with 35 mm Hg. No changes were detected in the later subcortical and cortical latencies. SEP amplitudes were also unchanged. These results in a controlled animal study corroborate the direction and magnitude of changes due to hypocapnia observed by other investigators in surgical patients. The magnitude of the changes indicates that SEP monitoring sensitivity is not compromised by clinically useful levels of induced hypocapnia during isoflurane anesthesia. Because hypocapnia may produce small SEP changes, baseline recordings should be acquired prior to initiation of hyperventilation. It is not warranted, however, to impute a severe deterioration of the SEP to hypocapnia alone, and causes must be sought elsewhere in a patient's status and management. PMID- 1583549 TI - The "Torrstick": a ruler calibrated in millimeters of mercury for measurement of hydrostatic pressure. AB - We have designed and constructed a ruler ("Torrstick") calibrated in millimeters of mercury for the measurement of hydrostatic pressure differences. Marks are placed on a measuring stick every 1.34 cm, to afford the best compromise between a column of 0.9% saline solution and a column of blood. Several uses for this ruler are proposed, including the measurement of central venous pressure. PMID- 1583550 TI - Sidestream versus mainstream carbon dioxide analyzers. PMID- 1583551 TI - Technology assessment of anesthesia monitors. AB - This essay argues that optimal utilization of anesthesia monitors requires careful technology assessment. This careful assessment is important because monitors may produce spurious or uninterpretable values, or they may damage patients. In addition, resources should be spent only for truly beneficial devices. The types of evidence that this essay describes for use in technology assessment include questions concerning data reliability, data interpretability, and data outcome. Considerable evidence bearing on technology assessment has already been amassed. I propose synthesizing this evidence by meta-analysis. Additional primary studies of technology assessment are also needed. PMID- 1583552 TI - Measurement of systolic blood pressure with a pulse oximeter. PMID- 1583553 TI - Thermal safety of a filamented pulmonary artery catheter. PMID- 1583554 TI - Effects of glucocorticoid and chemotherapy on the peritumoral edema and astrocytic reaction in experimental brain tumor. AB - To study the effects of glucocorticoids and chemotherapeutic agents on the pathophysiology of the tumor-induced brain edema, the site of Evans blue-albumin extravasation, the distribution of extravasated serum albumin, and the extent of local astrocytic reaction were examined in a rat model of implanted brain tumor. Experimental brain tumors were produced by implanting small pellets of Walker 256 carcinosarcoma into the cerebral cortex of Wistar rats. In the steroid group, rats were administered with intraperitoneal methylprednisolone succinate (15 mg/kg) daily on and after the 6th day postimplantation, and sacrificed on the 14th day. In the chemotherapy group, rats were given an intravenous injection of cyclophosphamide (30 mg/kg) on the 14th day, and sacrificed on the 21st day. Rats in the untreated group were sacrificed on the 14th day without any therapy. Each animal was sacrificed by the transcardiac perfusion with paraformaldehyde 30 min after intravenous injection of Evans blue. Firstly, coronal blocks of the brain were examined for Evans blue staining macroscopically. Paraffin embedded sections were studied for the Evans blue fluorescence and for the immunohistochemical reaction to serum albumin and GFAP. The examination of Evans blue demonstrated that the origin of extravasation of serum albumin was the tumor and the adjacent brain with dense tumor cell infiltration in any group of rats. The extravasated serum albumin distributed widely and the astrocytic reaction was prominent in the brain of the untreated group. A positive correlation was observed between the intensity of albumin immunoreaction and the degree of astrocytic proliferation. Chemotherapy effectively decreased the size of tumor and reduced the extravasation of serum albumin. The astrocytic reaction was however, not reduced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583556 TI - Maxillofacial prosthetics--an international perspective of the British status quo. AB - Maxillofacial prosthetics is a recognized subspecialty of prosthodontics. In considering the international status of maxillofacial prosthetics it is found that this unique and superspecialized discipline has a varied implementation both in terms of educational structures employed and clinical services provided. There is a dirth of available literature on education in maxillofacial prosthetics. The available literature is reviewed and the conclusion drawn is that very little undergraduate or postgraduate curriculum time is devoted to maxillofacial prosthetics in prosthodontic curricula. This, it is felt, adds to the ignorance of this important aspect of dentistry. Educational guidelines are reviewed and from this it is evident that the North American model of prosthodontic education and training differs greatly from the British one. This dichotomy appears to have impacted on prosthodontic training in other countries. Maxillofacial prosthetics enjoys special status in the United States but does not seem to be an important aspect of training in the British model. Indeed there is little evidence that maxillofacial prosthetics is an important focus of the British Consultant in Restorative Dentistry. Given the availability of the superb skills of the British trained maxillofacial prosthetic technicians and the hospital based restorative services, it is remarkable that the Restorative Consultants have not exercised their natural opportunity to lead internationally in both clinical and research areas, in this important discipline of dentistry. This must undoubtably pose a challenge for the British dental profession as a whole in the future. PMID- 1583555 TI - Does extent of surgery influence outcome for astrocytoma with atypical or anaplastic foci (AAF)? A report from three Radiation Therapy Oncology Group (RTOG) trials. AB - 103 patients with the diagnosis of AAF were identified from the RT/BCNU arms of 3 RTOG malignant glioma trials. Pre-treatment tumor size was less than 5 cm for 48% and greater than or equal to 5 cm for 52%, and tumor sites were frontal lobe in 55%, temporal in 25%, and parietal in 16%. Surgery consisted of biopsy for 30%, partial resection for 56%, and total resection for 14%. Extent of surgery correlated with age, with 81% of patients less than 40 undergoing partial/total resection vs. 60% of those over 40 (P = 0.019). The median survival time (MST) of patients undergoing partial/total resection was 49 mo., vs. 18 mo. for those biopsied only (P = 0.002). Patients with frontal location had longer MST than those with non-frontal lesions (MST: 49 vs. 25 mo., P = 0.047), while no survival difference was apparent by univariate analysis of tumor size. Multivariate analysis demonstrated that only younger age, frontal location, and smaller tumor size correlated significantly with extended survival. Extent of surgery was not predictive. The close correlation between young age and extensive surgery obscures the survival advantage for greater surgery seen with univariate analysis. Smaller tumor size and frontal location favorably influence outcome even when adjusted by age. PMID- 1583557 TI - Long-term follow-up of patients with orofacial discomfort complaints. AB - To a group of 113 patients who exhibited wide variation in orofacial and general complaints, which they related to the effects of dental material, a new questionnaire was sent 8-10 years after the first examination. Eight patients had died, and 23 individuals could not be contacted. Of the remaining 82 patients, 62 (76%) individuals completed the questionnaire. Almost two-thirds (29%) of the responding patients reported that they were now free from the previous symptoms, or that these symptoms were alleviated (35%). Dryness of the mouth and smarting tongue were the most frequent symptoms at the follow-up. Half of the patients (52%) thought they still needed treatment for their complaints, and several of them had visited many other therapists after the end of the treatment period at the Department. The treatment outcome and symptom development may be regarded as acceptable with regard to the severity and long duration of the original complaints. However, the prognosis was poor in a substantial proportion of the patients, and this group continued to be a high consumer of health-care resources. PMID- 1583558 TI - Preliminary observations on oral blood flow. AB - Using laser Doppler flowmetry (LDF), the blood microcirculation of the masseter muscle was studied in one healthy male subject performing clenching and grinding of the teeth. LDF suggested that blood flow was increased during clenching, and that it did not change appreciably during grinding. In one female patient (acute pain from myofibrostic lesion in masseter muscle), LDF suggested that flow within the lesion was increased during rest (postural position). In three healthy adults, subjected to simulated traumatic occlusion of the incisors, LDF suggested an absence of consistent changes in pulpal blood flow. PMID- 1583559 TI - Quantification of noble alloy used in 'porcelain-fused-to-metal' restorations. AB - High costs of gold alloys used in metal substructures of ceramo-metal restorations increase the cost of restorative treatment. This study determined the per unit weight of a noble metal alloy used in ceramo-metal crowns and three unit fixed-partial dentures. Generally, tooth size and extent of the metal substructure determined the quantity of alloy used. PMID- 1583560 TI - A transcranial radiographic examination of the temporal portion of the temporomandibular joint. AB - The temporomandibular joints of 20 human cadaver heads were examined by means of photography (gross anatomic images) and radiography (lateral oblique transcranial images), using the angle created by a line parallel to the Frankfurt horizontal and a line coinciding with the posterior slope of the most lateral (outermost) portion of the articular tubercle. This lateral eminence angle, made visible through an attached metal wire and a straight stick pin and pertaining to the outermost (zygomatic) portion of the eminentia, was about 45 degrees on both enlarged photographs and enlarged radiographs. There were no significant differences between the photographic and radiographic lateral eminence angles on the right and left sides. A more medially placed angle, yet pertaining to the lateral - and supposedly functional (protrusion) - portion of the glenoid fossa, was about 56 degrees on the right side and 51 degrees on the left side of the radiographic images. There were significant differences between the ipsilateral radiographic lateral and medial eminence angles. A separate decision-making analysis concluded that lateral oblique transcranial radiography is an effective, reliable, and inexpensive method for detection of bony changes in the lateral portions of the temporomandibular joints. PMID- 1583561 TI - Palliative care 2000: mapping the interface with cancer control. PMID- 1583562 TI - The epidemiology of palliative care in cancer. PMID- 1583563 TI - The costs of caring for cancer patients. PMID- 1583564 TI - Palliative care 2000--home care. AB - In summary, although I have reservations about the feasibility and cost effectiveness of regional palliative care centres as described in the report, my recommendations strongly concur with those of the Expert Panel on Palliative Care. With reference to home care, I would like to reiterate the following major points: There must be a major shift of resources into home care and the establishment of "in-the-home projects" within palliative care units. The control of suffering--palliative care--must be a full and equal partner in cancer care. The specialized aspect of home care will benefit from the direct network of a regional medical advisory committee, a quick-response and consultant team, and the integrated coordination system that a regional model offers. PMID- 1583565 TI - Palliative care 2000: where do we start? PMID- 1583566 TI - Hospitals and health care facilities. PMID- 1583567 TI - Cancer centres--their role in palliative care. PMID- 1583568 TI - A regional approach to palliative care services. PMID- 1583569 TI - Palliative care education in Canada: attacking fear and promoting health. PMID- 1583570 TI - Palliative care 2000: what's stopping us? PMID- 1583571 TI - Volunteer support services, a key component of palliative care. PMID- 1583572 TI - Ethical challenges in cancer care. PMID- 1583573 TI - Cancer 2000: the need for coordination. PMID- 1583574 TI - Prism adaptation for esotropia with a distance-near disparity. AB - A series of 64 patients who had surgery for esotropia with a distance-near disparity of at least 10 prism diopters was reviewed. Thirty-three patients were prism adapted for their distance deviation (PA distance). Thirty-one patients were prism adapted for near deviation (PA near). Both groups were divided into responders and nonresponders. In the PA distance group, 22 (67%) patients were responders. All responders had surgery for their prism-adapted angle. Postoperatively, 19 (86%) responders had fusion. Thirteen (68%) required bifocals to maintain fusion. In the PA near group, 21 (68%) patients were responders. All responders had surgery for their prism-adapted angle. Ninety-four percent of responders had fusion postoperatively. None needed bifocals for fusion postoperatively and none were overcorrected. The results show that those patients who were prism adapted for their near angle, responded with fusion, and had surgery for their full amount of esotropia at prism response obtained better postoperative fusion, without the need for a bifocal at near and without overcorrection at distance. PMID- 1583575 TI - Recovery of extraocular muscle function after adjustable suture strabismus surgery under local anesthesia. AB - Limited data exist on the recovery of ocular motility after adjustable suture strabismus surgery performed under local anesthesia. The timing of adjustment has been chosen empirically and has varied widely. We sought to more precisely quantify the recovery of motility by measuring ductions before and after surgery with a modified arc perimeter. Twenty-one eyes of 20 patients were studied. All patients underwent adjustable suture strabismus surgery under retrobulbar or peribulbar anesthesia using 2% lidocaine with hyaluronidase. Mean ductions orthogonal to the field of action of the operated muscle(s) returned to 90% of preoperative levels between 5 and 6 hours after injection. We recommend adjustment 6 or more hours after injection, or at least 5 to 6 hours postoperatively, when 2% lidocaine with hyaluronidase is used for local anesthesia. PMID- 1583576 TI - Dissociated vertical deviation: what is the most effective surgical approach? AB - In a retrospective study on 42 patients who had surgery between 1982 and 1990, the immediate as well as the long-term effect of three different surgical procedures on the dissociated vertical deviation (DVD) was studied. The procedures were: Faden operation of Cuppers of the superior rectus muscle 12 to 14 mm posterior to its insertion (10 patients); Faden operation of the superior rectus muscle 12 to 14 mm posterior to its initial insertion combined with a 3 millimeter recession of the muscle (7 patients); and large recession of the superior rectus muscle of 10 mm in a hang-loose technique (25 patients). The initial effect on the DVD was similar in the Faden group and in the group of the large recession. However, the long-term effect of the Faden operation was clearly superior to the large recessions. The Faden operation must be combined with a recession of the superior rectus muscle of at least 3 mm to avoid undercorrections if the original angle of deviation is larger than 14 prism diopters. The results are compared with those of other authors. PMID- 1583577 TI - Synergistic divergence: saccadic velocity analysis and surgical results. AB - The clinical findings are described in four patients with synergistic divergence (SD), an ocular motility disorder which is considered to be a variant of Duane retraction syndrome (DRS). Saccadic velocity studies in three patients demonstrated preserved abducting saccades in the affected eye with equally reduced amplitudes on both attempted abduction and adduction. The preserved saccades on attempted abduction of the affected eye, coupled with electromyographic evidence that shows maintenance of normal reciprocal innervation with respect to gaze on attempted abduction as dictated by Sherrington's law, strongly suggest that the abducens nerve is not necessarily absent or severely hypoplastic in this condition. One patient showed typical DRS in the contralateral eye and had a son with bilateral DRS, attesting to a possible genetic and etiologic relationship between SD and DRS. Three patients underwent strabismus surgery. Review of our surgical results and an analysis of the literature indicate that a crippling procedure to the ipsilateral lateral rectus muscle, such as extirpation, may be necessary to eliminate simultaneous abduction. Overcorrection did not occur following lateral rectus extirpation. PMID- 1583578 TI - Preservation of anterior ciliary vessels during strabismus surgery: a nonmicroscopic technique. AB - Preservation of anterior ciliary vessels (ACVs) during strabismus surgery using microscopic dissection techniques and the operating microscope has been previously described. We describe a technique using standard loupe magnification for vessel preservation, in 77 patients, ages 7 months to 69 years, who had surgery between January 1989 and September 1990. ACVs, with a small sheath of connective tissue, were dissected off the surface of the muscles and tendons using blunt and sharp dissection with Knapp iris hooks and Vannas scissors. Key elements of the dissection were sufficient separation of the vessel complex from the anterior tendon insertion and the use of blunt rather than sharp dissection. We successfully preserved 125 ACVs in 97 muscles. Ninety-five vessels were saved with 71 recessions, 14 with 13 resections, and 16 with adjustable sutures. The success rate of surgery was 85% in surgeries done either with or without anterior ciliary preservation. Vessel dissection time averaged 5 to 10 minutes per muscle. ACV preservation can be easily and successfully performed in routine strabismus cases. The procedure does not require the operating microscope and can be done under standard loupe (1.5 to 3.0 x) magnification. This procedure theoretically reduces the risk of anterior segment ischemia in situations where the patient is thought to be at significant risk for this complication. PMID- 1583579 TI - 18th annual Frank Costenbader Lecture. Fusion and suppression: development and loss. AB - A retrospective study (coauthored with Geraldine Tillson) of 118 patients with the congenital esotropia syndrome is described. All patients were aligned with surgery and, in some cases, glasses as well, within 10 prism diopters of orthotropia before the age of 2 years and had remained so aligned for at least a year. A standardized final examination was performed on patients over the age of 6 years, after at least 5 years' follow up, to study the effect of significant refractive error, amblyopia, nystagmus, dissociated vertical divergence, and inferior oblique overaction on the sensory outcome. None of the patients obtained central fusion. Fifty-three of 118 obtained peripheral fusion with at least 5 delta of fusional amplitude. Twenty-eight of the 53 fusers had stereopsis. The findings did not show any factors to explain why 65 did not obtain fusion. A congenital lack of the potential to develop fusion is postulated. The development of fusion and suppression is discussed with relevant references. Evidence is presented that the anatomical location of the lesion in central fusion disruption is in the midbrain. Fusion may be lost, in visual adults, without developing suppression from prolonged sensory deprivation. Examples include unilateral cataract, uncorrected unilateral aphakia, and unilateral severe herpetic keratitis. PMID- 1583580 TI - Motility disturbances after Molteno implants. AB - Molteno implants are gaining wide acceptance for refractory glaucoma in both children and adults. Such surgery led to vertical strabismus in three patients. Two children developed an inability to elevate the globe after Molteno implants were placed superiorly. One adult, whose Molteno implant was placed inferiorly, could not fully depress the globe postoperatively, and experienced vertical diplopia. This complication of Molteno implants was explored using forced duction testing and surgery. We feel a likely explanation for this is a Faden or posterior fixation suture effect induced by scarring under the rectus muscle. Patients undergoing this surgery should be counseled about possible postoperative diplopia, an especially devastating complication when the implant is placed inferiorly. PMID- 1583581 TI - Color vision screening of young children. AB - Early detection of congenital color vision defects is desirable, but school screening studies have been stymied by lack of a suitable test. We evaluated a new color vision test, the APT-5, for use by volunteer screeners in schools and preschools. The screeners tested 1794 children, ages 3 to 13 years, and found the APT-5 easy to use with young children ages 5 years and up. Children who failed the screening were recruited for diagnostic color vision testing; for the children ages 5 to 13 years, 56% of those who failed the screening were successfully recruited. Data analysis indicated that the false-positive rate in this age group was 1% to 2%, and that for boys in this age group the positive predictive value was 71% to 81%. Retest data indicated that most false-positives were not due to the test itself, but to other factors in the school screening situation. Two thirds of all children scored as abnormal by anomaloscopy were simple deuteranomalous, indicating that the APT-5 effectively identified even mild color defects. The results of this trial indicate that the APT-5 is suitable for school color vision screening of children ages 5 years and up. PMID- 1583582 TI - Infantile glaucoma associated with the Diamond-Blackfan syndrome. AB - Diamond-Blackfan syndrome is a rare congenital hematologic disorder characterized by isolated erythroid hypoplasia. Physical abnormalities such as short stature, thumb deformities, and ophthalmic findings including strabismus, hypertelorism, and microphthalmos have been reported to occur with this disease entity. We describe two patients with this blood dyscrasia and infantile glaucoma with trabeculodysgenesis. Both patients underwent multiple surgical procedures to control their glaucoma. The patients were on chronic systemic adrenal corticosteroid therapy for their anemia, which caused some confusion regarding the etiology of their glaucoma. To our knowledge, this is the first report of an association of infantile glaucoma with Diamond-Blackfan syndrome. We hope this report will encourage early recognition and treatment of glaucoma in patients with this disorder. PMID- 1583583 TI - Culture and moral judgment: how are conflicts between justice and interpersonal responsibilities resolved? AB - A 2-session study examined Indian and American adults' and children's (N = 140) reasoning about moral dilemmas involving conflicts between interpersonal and justice expectations. Most Indians gave priority to the interpersonal expectations, whereas most Americans gave priority to the justice expectations. Indians tended to categorize their conflict resolutions in moral terms. In contrast, when Americans gave priority to the interpersonal alternatives, they tended to categorize their resolutions in personal terms. Results imply that Indians possess a postconventional moral code in which interpersonal responsibilities are seen in as fully principled terms as justice obligations and may be accorded precedence over justice obligations. Findings also suggest that a personal morality of interpersonal responsiveness and caring is linked to highly rights-oriented cultural views, such as those emphasized in the United States. PMID- 1583584 TI - Does memory affect judgment? Self-generated versus recall memory measures. AB - Most evidence regarding the independence of memory and judgment comes from studies that used memory measures consisting of Ss' recall of raw input data (recall measures). Such evidence provides the primary support for on-line judgment formation. The results of 2 experiments suggest that self-generated memory measures capture the contents of memory at the time of judgement more effectively than recall measures and, accordingly, are more likely to provide evidence that memory and judgment are related. When directly compared, a self generated measure provided evidence of a memory-judgment relationship and a recall measure did not. Thus, memory-based judgment formation may be more prevalent than the on-line processing literature suggests. PMID- 1583585 TI - Affect and stereotyping: the effect of induced mood on distinctiveness-based illusory correlations. AB - In 2 studies, the effects of mood on the formation of distinctiveness-based illusory correlations were examined. After exposure to stimuli inducing positive, neutral, or negative mood, Ss read information about behaviors performed by members of 2 groups in an illusory correlation paradigm. In both experiments, only Ss in a neutral mood formed illusory correlations. In addition, Experiment 2 assessed Ss' processing latencies as a means of investigating differential attention to distinctive behaviors. Only Ss in a neutral mood differentially attended to the minority group's infrequent behaviors. Induced mood apparently interfered with the processing necessary to differentially encode distinctive stimuli, undermining the illusory correlation effect. PMID- 1583586 TI - Personality feedback and situational norms can control stereotyping processes. AB - Impressions are influenced by motivations stemming primarily from the target (e.g., interdependence), 3rd parties (e.g., accountability or time pressure), or the self. The current studies investigate motivations stemming primarily from the self. In Study 1, Ss were given dispositional feedback about their abilities to categorize or to individuate. In Study 2, they were given situational information about the appropriate norms to categorize or to individuate. As predicted, dispositional feedback influenced low self-monitors, and situational information influenced high self-monitors. Both altered attention to potentially individuating category-inconsistent attributes as well as requests for additional information. Causal models further illuminated the mediating processes. These results suggest that people's flexible self-concepts are an important source of motivation in impression formation. PMID- 1583587 TI - Outcasts in a white-lie society: the enigmatic worlds of people with negative self-conceptions. AB - Although people with negative self-views want to be liked at some level, they repeatedly enact behaviors that alienate their relationship partners. Why? One possibility is that such persons reside in social environments that offer them little insight into what they are doing wrong. Although persons who had negative self-views elicited unfavorable reactions, they did not appreciate this fact because their interaction partners concealed their aversion behind a facade of kind words. To be sure, the interaction partners of people with negative self views tended to leak their disdain nonverbally. These negative nonverbal messages proved to be uninformative, however, because people with negative self-views overlooked them. These data imply that people with negative self-views may live in social worlds in which they are deprived of corrective feedback that could allow them to improve themselves. PMID- 1583588 TI - Effects of fantasy contexts on children's learning and motivation: making learning more fun. AB - Two studies examined the effects of embedding instructional materials in relevant fantasy contexts on children's motivation and learning. In Study 1, Ss showed marked preferences for computer-based educational programs that involved fantasy elements. In Study 2, Ss worked with these programs for 5 hr. One program presented purely abstract problems. Others presented identical problems within fantasy contexts. Some Ss chose among 3 fantasies; others were assigned identical fantasies. Tests on the material occurred before, immediately after, and 2 weeks after the experimental sessions. Ss showed significantly greater learning and transfer in the fantasy than in the no-fantasy conditions. Having a choice of fantasies made no difference. Motivational and individualization strategies for enhancing interest and promoting learning are discussed. PMID- 1583589 TI - Job experiences over time, multiple roles, and women's mental health: a longitudinal study. AB - Are changes over time in the quality of a woman's job associated with changes in her psychological distress? Do family roles moderate these relationships? We addressed these questions using longitudinal data from a 2-year 3-wave study of a stratified random sample of 403 employed women who varied in occupation, race, partnership, and parental status. After estimating individual rates of change for each woman on each of the predictors and the outcome, we modeled the relationships between family role occupancy and change in job-role quality on the one hand, and change in psychological distress on the other. Among single women and women without children, as job-role quality declined, levels of psychological distress increased. Among partnered women and women with children, change in job role quality was unrelated to change in psychological distress. PMID- 1583590 TI - Shamed into anger? The relation of shame and guilt to anger and self-reported aggression. AB - The relation of shame and guilt to anger and aggression has been the focus of considerable theoretical discussion, but empirical findings have been inconsistent. Two recently developed measures of affective style were used to examine whether shame-proneness and guilt-proneness are differentially related to anger, hostility, and aggression. In 2 studies, 243 and 252 undergraduates completed the Self-Conscious Affect and Attribution Inventory, the Symptom Checklist 90, and the Spielberger Trait Anger Scale. Study 2 also included the Test of Self-Conscious Affect and the Buss-Durkee Hostility Inventory. Shame proneness was consistently correlated with anger arousal, suspiciousness, resentment, irritability, a tendency to blame others for negative events, and indirect (but not direct) expressions of hostility. Proneness to "shame-free" guilt was inversely related to externalization of blame and some indices of anger, hostility, and resentment. PMID- 1583591 TI - Individual differences in anterior brain asymmetry and fundamental dimensions of emotion. AB - This research assessed whether individual differences in anterior brain asymmetry are linked to differences in basic dimensions of emotion. In each of 2 experimental sessions, separated by 3 weeks, resting electroencephalogram (EEG) activity was recorded from female adults during 8 60-s baselines. Mean alpha power asymmetry across both sessions was extracted in mid-frontal and anterior temporal sites. Across both regions, groups demonstrating stable and extreme relative left anterior activation reported increased generalized positive affect (PA) and decreased generalized negative affect (NA) compared with groups demonstrating stable and extreme relative right anterior activation. Additional correlational analyses revealed robust relations between anterior asymmetry and PA and NA, particularly among subjects who demonstrated stable patterns of EEG activation over time. Anterior asymmetry was unrelated to individual differences in generalized reactivity. PMID- 1583592 TI - Differential accuracy in person perception across traits: examination of a functional hypothesis. AB - Although strangers can assess certain traits of unacquainted others with moderate validity, overall validity is low. Differential validity across traits may be due to (a) the extent to which targets display valid cues or (b) the extent to which perceivers validly use cues. A functionalist perspective suggests that valid cue utilization should vary with how important the consequences of accurate trait assessment are. It was predicted from this perspective that perceivers would judge strangers' sociosexuality more accurately than 3 other traits--social potency, social closeness, and stress reaction. Perceivers viewed 1-min videotaped segments of targets being interviewed and rated them on the 4 traits. Ratings were correlated with target-reported trait measures. As predicted, perceivers' ratings of male sociosexuality agreed relatively well with self reports. This effect was moderated by sex of target and sex of perceiver. PMID- 1583593 TI - Mood-induced self-focused attention. AB - The influence of mood on self-focused attention was explored in 2 experiments involving the induction of moods in the laboratory. Experiment 1 tested the hypothesis that mood states, whether pleasant or unpleasant, induce self-focused attention. This hypothesis was supported using a sentence completion task as the measure of self-focus. Experiment 2 replicated Experiment 1 results using a measure of self-complexity as an index of self-focus. These experiments provide support for a model of affect-action sequences the first step of which entails the turning of attention toward the self in response to the arousal of affect. PMID- 1583594 TI - Histologic effects of smokeless tobacco and alcohol on the pouch mucosa and organs of the Syrian hamster. AB - This study's intent was to measure the histologic effects of smokeless tobacco and alcohol on the buccal pouch mucosa and internal organs of male Syrian hamsters. Eighty hamsters were divided into four groups: tobacco only, alcohol only, tobacco and alcohol, and negative control. 200 mg of smokeless tobacco were placed in each pouch of the tobacco groups five times a week. In the alcohol groups, 2 ml of 15% ethyl alcohol were placed in each pouch five times a week. The negative control group had mechanical stimulation of the right pouch to simulate the placement of the tobacco. After 26 wk the animals were sacrificed with pouches and abdominal organs removed. Alterations were observed in the abdominal organs, but not of statistical significance. However, significant acanthosis of the pouch epithelium was noted in the tobacco and tobacco and alcohol groups. This study reaffirms the lack of carcinogenic potential of smokeless tobacco upon the hamster pouch mucosa and internal organs. PMID- 1583595 TI - Periodontal health in 200 HIV-positive patients. AB - Two hundred HIV-positive subjects were surveyed to determine their periodontal health status. Particular attention was given to the occurrence of a severe and rapidly progressing form of periodontal disease designated "HIV-associated periodontitis", which has been reported as being unique to AIDS patients. Among the subjects comprising the cohort, 85 subjects had good gingival health, 59 subjects exhibited gingivitis, 49 cases of adult periodontitis were observed, 5 subjects presented with advance adult periodontitis, and 2 cases of necrotizing ulcerative periodontitis (NUP) were found within the group. The periodontitis of the patients in this survey did not have unique or pathognomonic characteristics which could set their periodontal disease apart from the periodontal disease seen in HIV negative population. PMID- 1583596 TI - Pyostomatitis vegetans: report of three cases and review of the literature. AB - Pyostomatitis vegetans is a rare condition of the mouth frequently associated with chronic inflammatory bowel disease. It is characterized by miliary abscesses and superficial erosions affecting a hyperplastic, soft and friable oral mucosa. Three cases are presented here and used as a basis for reviewing the literature and discussing the differential diagnosis, etiology and treatment of this unusual condition. PMID- 1583597 TI - Effect of ionizing radiation on sympathetic nerve function in rat parotid glands. AB - Ionizing radiation (IR) irreversibly damages salivary glands. The pathologic mechanism is unknown. Previously we reported that parotid serous acinar cells may not be the primary site of damage by IR. The purpose of this study was to determine if IR alters sympathetic nerve function in rat parotid glands. Male adult rats received a single dose of radiation (20 Gy) to the head and neck. Three days after IR, parotid saliva secretion induced by norepinephrine (NE) was completely blocked. Catecholamine uptake and metabolism were studied by injecting [3H] dopamine ([3H]DA) into irradiated rats, as a bolus. After 60 min, animals were sacrificed and the parotid gland, submandibular gland, and left ventricle removed. Tissue contents of [3H]DA and [3H]NE, identified by HPLC, were unaffected by IR. The results indicate that IR abolishes acinar responsiveness to NE without affecting parotid sympathetic nerve function. PMID- 1583598 TI - Adenomatoid odontogenic tumorlike lesion in a male Wistar rat. AB - An odontogenic tumor in the maxilla of a male Wistar rat is described. The tumor consisted of large epithelial areas with peripheral palissading and with juxtaepithelial material resembling dentin. The neoplastic odontogenic epithelium seems capable of inducing peridental mesenchyme to form a kind of dental hard tissue normally not present at that site. PMID- 1583599 TI - Oral alimentary tract cyst. AB - A cyst in the floor of the mouth of a 2-yr-old boy was characterized by smooth muscle tissue with an overlying epithelial lining of varying morphology including gastric mucosa. The combination of smooth muscle with a variety of epithelial linings argues against the "misplaced anlage" histogenesis. PMID- 1583600 TI - HLADR+ Langerhans cell (LC) numbers in human lingual epithelium. PMID- 1583601 TI - Immunohistochemical localization of c-myc oncogene product in oral papilloma. AB - The expression of c-myc oncogene products in oral papillomas was studied by using an immunohistochemical method. The oncogene products were detected in 17(70.8%) of the 24 oral papillomas under study. The expression of the products was evaluated, and the histologic localization in proliferating epithelial cells of the oral papillomas was determined. In the basal cell layer, the products were detected in the nuclei of 16 oral papillomas, and in the cytoplasm of 12 oral papillomas. In the nuclei of cells in the spinous cell layer, the products were detected in 4 oral papillomas, and in the cytoplasm of 13 oral papillomas. In the keratinized cells, the products were not detected in the nuclei, but they were identified in the cytoplasm of three oral papillomas. The results suggested that the c-myc oncogene product might play an important role for proliferation and differentiation of the oral papilloma. PMID- 1583602 TI - Postnatal development of central auditory frequency maps. AB - In the early postnatal period of many mammals and in the perihatching period of chicks the auditory ranges are restricted to the species-specific low- and mid frequency ranges. During subsequent development, the high frequency hearing expands (depending on the species) by 1-4 octaves. Adult-like audition is established between the 4th and the 7th week. It is still discussed controversially, how the extension of the auditory ranges relates to the maturation of orderly frequency representation in the cochleae of the respective species. The present review summarizes investigations of the development of tonotopy in nuclei of the central auditory system, and discusses how the centrally acquired data might contribute to the understanding of the maturation of cochlear stimulus transduction and to the development of frequency maps. PMID- 1583603 TI - The stopping response of Xenopus laevis embryos: behaviour, development and physiology. AB - 1. When Xenopus laevis embryos swim into an obstruction they usually stop. This stopping response to stimulation on the head is present from stage 28 to 45. At stage 37/38 it is more reliable in restrained than in free-swimming animals, and to stimuli to the cement gland than to the head skin. 'Fictive' swimming also stops reliably after the same stimuli but struggling and 'fictive' struggling do not. 2. Discharge of deformation-sensitive trigeminal sensory neurons in response to pressure on the cement gland or head skin precedes the 'fictive' stopping response. When the embryo hangs from cement gland mucus, trigeminal neurons are active and the embryo is less responsive to stimulation. 3. Lesions of the central nervous system have allowed us to draw the following conclusions about this inhibitory pathway: (a) either the cement gland or the head skin must be intact; (b) one trigeminal ganglion is both sufficient and necessary; (c) the pathway is independent of the forebrain and midbrain; (d) it can take an ipsilateral or contralateral route through the hindbrain; (e) at least two hindbrain interneuron components are involved. 4. A similar stopping response is present in embryos and larvae of the urodele Ambystoma mexicanum. PMID- 1583604 TI - Social stimuli fail to act as entraining agents of circadian rhythms in the golden hamster. AB - The ability of social stimuli to act as entraining agents of circadian rhythms was investigated in golden hamsters (Mesocricetus auratus). In a first experiment, pairs of male hamsters (one of them enucleated and the other intact) were maintained under a ligh-dark (LD) cycle with a period of 23.3 h. Running wheel activity was recorded to determine the effect of social interaction on the free-running circadian rhythm of activity. In several pairs, general activity and body temperature were also recorded. In all pairs the intact animals entrained to the LD cycle, whereas the activity rhythms of the enucleated animals free-ran with periods of approximately 24 h and showed no apparent sign of synchronization or relative coordination with the other member of the pair. In a second experiment, male hamsters maintained in constant darkness received pulses of social interaction, which have been reported to induce phase shifts of the activity rhythm. Consistent phase shifts in the running-wheel activity rhythm were not induced by the social pulses in our experiment. These results suggest strongly that social stimuli are not effective entraining agents of circadian rhythms in the golden hamster. PMID- 1583605 TI - Elevated temperature alters the ionic dependence of amine-induced pacemaker activity in a conditional burster neuron. AB - The anterior burster neuron of the lobster (Panulirus interruptus) stomatogastric ganglion is a conditional burster that functions as the primary pacemaker for the pyloric motor network. When modulatory inputs to this cell are blocked, it loses its bursting properties and becomes quiescent. Applications of the monoamines, dopamine, octopamine or serotonin restore rhythmic bursting in this cell (Flamm and Harris-Warrick 1986). At 15 degrees C, serotonin- and octopamine-induced oscillations depend critically upon sodium entry (blocked by low sodium saline or tetrodotoxin); dopamine-induced oscillations depend upon calcium entry (blocked by reduced extracellular calcium; Harris-Warrick and Flamm 1987). We show here that the ionic dependence of amine-induced oscillations in the anterior burster cell differs at 15 and 21 degrees C. At 21 degrees C, all amines have the potential to induce rhythmic oscillations in saline containing tetrodotoxin. At the elevated temperature and in tetrodotoxin, both calcium and sodium currents are essential for the maintenance of dopamine-induced oscillations; serotonin induced oscillations do not depend upon either calcium or sodium alone; octopamine-induced oscillations do not depend upon calcium and show a variable dependence upon sodium. Thus, multiple ionic mechanisms, which vary with both the modulator and the ambient temperature, can be recruited to support rhythmic activity in a conditional burster neuron. PMID- 1583606 TI - FMRFamide modulates the action of phase shifting agents on the ocular circadian pacemakers of Aplysia and Bulla. AB - The eye of the marine mollusk Aplysia californica contains a photo-entrainable circadian pacemaker that drives an overt circadian rhythm of spontaneous compound action potentials in the optic nerve. Both light and serotonin are known to influence the phase of this ocular rhythm. The current study evaluated the effect of FMRFamide on both light and serotonin induced phase shifts of this rhythm. The application of FMRFamide was found to block serotonin induced phase shifts but, by itself, FMRFamide did not cause significant phase shifts. Furthermore, the effects of FMRFamide on light-induced phase shifts appeared to be phase dependent (i.e., the application of FMRFamide inhibited light-induced phase delays but actually enhanced the magnitude of phase advances). As in Aplysia, the eye of Bulla gouldiana also contains a circadian pacemaker. In Bulla, FMRFamide prevented light-induced phase advances and delays. Although FMRFamide alone generated phase dependent phase shifts, it did not cause phase shifts at the phases where it blocked the effects of light. These data demonstrate that FMRFamide can have pronounced modulatory effects on phase shifting inputs to the ocular pacemakers of both Aplysia and Bulla. PMID- 1583607 TI - Discharge patterns of cochlear ganglion neurons in the chicken. AB - Physiological recordings were made of the compound action potential from the round window and single neurons in the cochlear ganglion of normal adult chickens (Gallus domesticus). The compound action potential threshold to tone bursts decreased from approximately 42 dB at 0.25 kHz to 30 dB between 1 and 2 kHz and then increased to 51 dB at 4 kHz. Most of the cochlear ganglion cells had characteristic frequencies below 2 kHz and the thresholds of most neurons were roughly 30-35 dB lower than the compound action potential thresholds. At any given characteristic frequency, thresholds varied by as much as 60 dB and units with the highest thresholds tended to have the lowest spontaneous rates. Spontaneous discharge rates ranged from 0 to 200 spikes/s with a mean rage of 86 spikes/s. Interspike interval histograms of spontaneous activity often contained regular peaks with the time interval between peaks approximately equal to 1/(characteristic frequency). Tuning curves were sharply tuned and V-shaped with approximately equal slopes to the curves above and below characteristic frequency. Q10dB and Q30dB values for the tuning curves increased with characteristic frequency. Post stimulus time histograms showed sustained firing during the stimulus and were characterized by a slight-to-moderate peak at stimulus onset. Most units showed vigorous phase-locking to tones at characteristic frequency although the degree of phase-locking declined sharply with increasing characteristic frequency. Discharge rate-level functions at characteristic frequency had a mean dynamic range of 42 dB and a mean saturation firing rate of 327 spikes/s. In general, the firing patterns of cochlear ganglion neurons are similar in most respects to those reported in other avians, but differ in several important respects from those seen in mammals. PMID- 1583608 TI - Azimuthal sound localization in the European starling (Sturnus vulgaris): I. Physical binaural cues. AB - The physical measurements reported here test whether the European starling (Sturnus vulgaris) evaluates the azimuth direction of a sound source with a peripheral auditory system composed of two acoustically coupled pressure difference receivers (1) or of two decoupled pressure receivers (2). A directional pattern of sound intensity in the free-field was measured at the entrance of the auditory meatus using a probe microphone, and at the tympanum using laser vibrometry. The maximum differences in the sound-pressure level measured with the microphone between various speaker positions and the frontal speaker position were 2.4 dB at 1 and 2 kHz, 7.3 dB at 4 kHz, 9.2 dB at 6 kHz, and 10.9 dB at 8 kHz. The directional amplitude pattern measured by laser vibrometry did not differ from that measured with the microphone. Neither did the directional pattern of travel times to the ear. Measurements of the amplitude and phase transfer function of the starling's interaural pathway using a closed sound system were in accord with the results of the free-field measurements. In conclusion, although some sound transmission via the interaural canal occurred, the present experiments support the hypothesis 2 above that the starling's peripheral auditory system is best described as consisting of two functionally decoupled pressure receivers. PMID- 1583609 TI - Differential distribution of ampullary and tuberous processing in the torus semicircularis of Eigenmannia. AB - Gymnotiform electric fish sense low- and high-frequency electric signals with ampullary and tuberous electroreceptors, respectively. We employed intracellular recording and labeling methods to investigate ampullary and tuberous information processing in laminae 1-5 of the dorsal torus semicircularis of Eigenmannia. Ampullary afferents arborized extensively in laminae 1-3 and, in some cases, lamina 7. Unlike tuberous afferents to the torus, ampullary afferents had numerous varicosities along their finest-diameter branches. Neurons that were primarily ampullary were found in lamina 3. Neurons primarily excited by tuberous stimuli were found in lamina 5 and, more rarely, in lamina 4. Cells that had dendrites in lamina 1-3 and 5 could be recruited by both ampullary and tuberous stimuli. These bimodal cells were found in lamina 4. During courtship, Eigenmannia produces interruptions of its electric organ discharges. These interruptions stimulate ampullary and tuberous receptors. The integration of ampullary and tuberous information may be important in the processing of these communication signals. PMID- 1583610 TI - Breast reconstruction with the free TRAM flap after breast cancer surgery. AB - The authors' experiences with 34 free lower TRAM flap transfers, in which 19 primary reconstructions and 15 secondary reconstructions were successfully achieved, are reviewed. The free TRAM flap yielded better results than the pedicled TRAM flap in cases where reconstruction of the infraclavicular and anterior axillary areas, as well as of the breast mound itself, was required. PMID- 1583611 TI - Replantation of the upper extremity severed at the level of the ulnar joint. AB - Two cases of upper extremity replantation at the level of the ulnar joint are presented. In both cases, the ulnar joint and adjacent anatomic functional structures were destroyed in accidents and excised during surgery. Some functional rehabilitation of the replanted extremities was obtained. In one case, the grasp function of the hand was recovered through primary use of the muscular apparatus of the upper arm. In another patient, the function of the lost ulnar joint was restored through microsurgical autotransplantation of the vascularized first metatarsophalangeal joint of the foot. PMID- 1583612 TI - Microvascular digit transposition following a two-digit amputation in an infant. AB - Multiple digit amputations in children demand special consideration to make subsequent hand function optimal. Replanted digits in children have a comparatively lower viability rate, but those that do survive usually go on to excellent function. In this case, an amputated thumb was severely mangled and not suitable for replantation. An amputated index finger was transposed to the thumb position. A six-month postoperative follow-up of the transposed digit confirmed satisfactory joint motion, restored sensibility, and unimpaired digit growth. The 11-month-old infant described is the youngest patient ever reported to have undergone a successful emergency microvascular digit transposition. PMID- 1583613 TI - Gnostic rings: usefulness in sensibility evaluation and sensory reeducation. AB - The benefit of additional clinical tools for quantifying patients' ability to recognize objects is clear, as well as its correlation with the moving two-point discrimination test. The recognition of letters is such a tool. The authors describe gnostic rings, an additional technique, that is useful for clinical sensibility testing, as well as for sensory reeducation. PMID- 1583614 TI - A new vascularized nerve graft model in the rabbit. AB - The macro- and microanatomy of the rabbit median nerve were studied for the purpose of developing a vascularized nerve graft (VNG) model. A segment of median nerve was then designed as a vascularized graft to serve as a model. This model consists of a 1-cm long median nerve segment and its accompanying brachial artery and vein 3 cm in length, with an arteriovenous fistula created distally. The model was tested by using the VNG to repair an intratemporal facial nerve defect and proven to be reliable. Its monofascicular pattern and diameter match those of the reconstructed facial nerve, making this model unique, compared to other models previously described. PMID- 1583615 TI - The effect of calcitonin on osteoporosis of the rat hind limb induced by denervation and isograft transplantation. AB - The effects of both isograft transplantation and immobilization by sciatic and femoral neurotomy on bone changes in the tibia were studied in adult rats. The effects of the administration of (Asu1,7)-eel calcitonin on bone changes in the tibia induced by the same procedures were also examined. Bone volume, dry weight, ash weight, calcium weight, and strength were measured. Bone density of the tibia in the isograft transplantation group was less than that of the immobilization group, indicating that the osteoporosis induced by sciatic and femoral neurotomy and isograft transplantation differed. (Asu1,7)-eel calcitonin increased tibia bone density, ash per volume, calcium per volume, and phosphorus per volume, when subjected to isograft transplantation but not in sciatic neurotomy. Bone atrophy induced by immobilization through sciatic and femoral neurotomy and that induced by isograft transplantation were thus shown to differ. PMID- 1583616 TI - Repair of different sized nerve defects using degenerated muscle grafts with vascular implantation: an experimental study in the rat. AB - In order to explore the repair of nerve defects of different sizes using degenerated muscle grafts with vascular implantation [DMG(+VI)], 10-, 15-, 20-, and 25-mm sciatic nerve defects in the rat were bridged. After eight months, the muscle grafts were reconstructed to the nerve-like tissues. There was better revascularization in the grafts because of vascular implantation. Regenerated axons could grow through 10-, 15-, 20-, and 25-mm muscle grafts to the distal nerve stump and ultimately to the target-organs. The regenerated axons were well myelinated and nerve conduction was recovered. However, as the graft length increased, the quantity of regenerated axons gradually decreased and the function of the regenerated axons was affected. PMID- 1583617 TI - The effects of cryosurgery and cryoprotectants on peripheral nerve function. AB - Cryosurgery has many advantages in the treatment of musculoskeletal tumors, but complications can occur, with injuries to the peripheral nerves. Cryoprotectants such as dimethylsulfoxide (DMSO) and glycerol enhance the in vitro survival of cultured Schwann cells, but they have not been studied in vivo. In vitro, 10 percent DMSO provided the maximal survival after freezing to -80 degrees C. The neurologic recovery of a peripheral nerve, following cryoinjury and using liquid nitrogen, was evaluated both with and without pretreatment of the nerve with 10 percent DMSO. There were three experimental groups: 1) one sham operation; 2) with freezing of the sciatic nerve; and 3) with freezing of the sciatic nerve after treatment with DMSO. Gait analyses (sciatic function index, SFI), muscle weights, and histologic evaluations were performed in order to follow the neurologic recovery over a ten-week period. The freezing-only group and the sham operated control had an excellent functional recovery in terms of the SFI following surgery (-4.2 percent +/- 4.0 percent and -2.4 percent +/- 5.7 percent, respectively), in contrast to the freezing group with DMSO (-34.1 percent +/- 5.5 percent, p less than .01). The average tibialis anterior muscle weight, reported as the ratio of the operated to the unoperated limb (88.2 percent +/- 1.0 percent) in the freezing-only group, was greater than the average for the freezing-with-DMSO-treated group (70.6 percent +/- 3.9 percent, p less than .01). Cryoprotectants are routinely used to optimize the survival of cells in tissue culture. However, DMSO not only failed to protect peripheral nerves from cryoinjury, but it also inhibited functional recovery. PMID- 1583618 TI - Continuous postoperative free-flap monitoring with an EKG-interfaced photoplethysmograph. AB - A compact battery-operated tissue-perfusion monitor has been developed which continuously displays photoplethysmograph waveforms on bedside EKG monitors. The device has been of proven utility in the postoperative monitoring of free-flap recipients. PMID- 1583619 TI - Down regulation of cerebral cortical 3H imipramine binding sites during chronic antidepressant treatment is independent of the central serotonergic innervation. AB - The effects of chronic antidepressant (AD) administration (amitryptiline 12 mg/Kg i.p., 20 days) on cerebral cortical [3H] imipramine binding sites were examined in control rats and in serotonergic denervated animals. Both treatments independently reduced the density of [3H] imipramine binding sites by 33-40%. Animals submitted to both treatments showed a slightly higher decrease in the Bmax (-50%). No alterations were observed in the apparent dissociation constant. Preincubation of cerebral cortical synaptosomal membranes with Triton X-100 (0.2% v/v), which preferentially dissolves the presynaptic component of the synaptosomes, reduced by 40% the maximal number of [3H] imipramine binding sites in control rats. In chronic AD treated rats or in serotonergic lesioned rats, membranes preincubated with Triton X-100 showed a 30% decrease in the number of [3H] imipramine sites in comparison to the sham group. The combination of both treatments produced an even larger decrease in the density of [3H] imipramine binding sites in Triton X-100 treated membranes (-55%) compared to the sham group. Taken together, these results strongly suggest that cerebral cortical [3H] imipramine binding sites located both pre- and postsynaptically, are down regulated by the long term AD administration independently of the integrity of the central serotonergic system. PMID- 1583620 TI - Characterization of human striatal A2-adenosine receptors using radioligand binding and photoaffinity labeling. AB - The adenosine agonist [3H]CGS21680 (2-[4-[[2-carboxyethyl]phenyl]ethylamino]-5'- N-ethylcarboxamidoadenosine) bound to A2 receptors in human striatal membranes with a Kd of 17.8 +/- 1.1 nM and a Bmax of 313 +/- 10 fmol/mg protein. The addition of 100 microM GTP diminished both the affinity of agonist radioligand for A2 adenosine binding sites and the total binding, resulting in Kd and Bmax values of 28.6 +/- 1.0 nM and 185 +/- 22 fmol/mg of protein. Adenosine ligands competed for [3H]CGS21680 with the expected potency order. The adenosine antagonist [3H]XAC (8-[4-[[[[(2-aminoethyl)-amino]carbonyl]methyl] oxy]phenyl] 1,3-dipropylxanthine), although A1-selective in the rat, binds to human striatal A2 receptors with high affinity. 25 nM CPX (8-cyclopentyl-1,3-dipropylxanthine), an A1-selective antagonist, was added to the incubation medium and effectively eliminated 91% of [3H]XAC (1 nM) binding to human A1 receptors, yet preserved 90% of binding to A2 receptors. [3H]XAC exhibited saturable, specific binding (50% of total) to A2 sites with a Kd of 2.98 +/- 0.54 nM and a Bmax of 0.71 +/- 0.23 pmol/mg protein (25 degrees C, non-specific binding defined with 100 microM NECA). The potency order for antagonists against 1 nM [3H]XAC was CGS15943A greater than XAC approximately PD115,119 greater than PAPA-XAC greater than CPX greater than HTQZ approximately XCC approximately CP-66,713 greater than theophylline approximately caffeine, indicative of an A2-type binding site. A2a receptors were found to be present in the human cortex, albeit at a much lower density than in the striatum. Photoaffinity labeling using 125I-PAPA-APEC revealed a molecular weight of 45K, but proteolytic cleavage was observed, resulting in fragments of MW 43K and 37K. In the absence of proteolytic inhibitors the 37K fragment, which still bound 125I-PAPA-APEC, was predominant. PMID- 1583622 TI - Cytosolic type II estrogen binding site in rat uterus: specific photolabeling with estrone. AB - A low affinity (Kd = 30 nM), large capacity (Bmax = 2.6 pmol/g tissue) estrogen binding site was photolabeled from estradiol-stimulated rat uterus cytosol. To maximize levels of this binding site and reduce those of the type I binding site, ovariectomized rats were injected with high doses of estradiol (10 micrograms per day) for four days with the last injection two hours before sacrifice. This treatment depleted type I estrogen receptors from the cytosol (by 90%) and raised levels of type II sites in the nucleus without affecting cytosolic type II levels. The type II estradiol binding sites were distinguished from the type I sites on the basis of their dissociation kinetics, pH-sensitivity and their behavior towards potassium chloride, somatostatin, sodium thiocyanate, sulfhydryl reagents and ammonium sulfate precipitation. These type II binding sites could be covalently photolabeled with tritiated estrone. A molecular weight of 43 kDa was found on SDS PAGE. PMID- 1583621 TI - Elimination of ascorbic acid-induced membrane lipid peroxidation and serotonin receptor loss by Trolox-C, a water soluble analogue of vitamin E. AB - Ascorbic acid is commonly used as an antioxidant to prevent the decomposition of ligands in neurotransmitter receptor studies, but may alter biological membranes by initiating lipid peroxidation in the presence of physiologic metal ions. The aim of the present study was to characterize the effect of ascorbic acid-induced lipid peroxidation on an applicable membrane receptor and to examine an appropriate antioxidant system. Ascorbic acid generated significant lipid peroxidation (5.5 to 45 fold increase in malonaldehyde levels) in three diverse tissues having different membrane properties: bovine brain, mouse teratoma, and rat kidney. In membranes from bovine cerebral cortex, ascorbate-induced lipid peroxidation was associated with a 26% decrease in [3H]-serotonin receptor binding (Bmax = 159 +/- 11 from control of 216 +/- 10 fmol/mg protein), with no significant change in KD. Trolox-C, a water soluble analogue of vitamin E, completely blocked the ascorbate-induced loss of serotonin receptor binding in brain membranes, and the combination of Trolox-C and ascorbate prevented [3H] serotonin decomposition in solution. Trolox-C also prevented ascorbate-induced lipid peroxidation in brain, teratoma, and kidney membranes. Lipid peroxidation may be a significant factor in the ascorbate-induced alteration of brain membranes as reflected by reduced binding to serotonin receptors. The combination of Trolox-C (200 microM) and ascorbic acid (1.0 mM) maintains a protective environment for oxygen sensitive neurotransmitters while blocking the deleterious effects of ascorbic acid on lipid membranes. PMID- 1583623 TI - Biochemical characterization of a subtype pancreatic cholecystokinin receptor and of its agonist binding domain. AB - This study was undertaken in order to improve photoaffinity labelling efficiency of pancreatic cholecystokinin receptor by the cleavable probe 125I-ASD (Thr28,Ahx31)-CCK-25-33 and to further characterize the denaturated receptor and its agonist binding domain. Membrane bound pancreatic cholecystokinin receptor was specifically labelled by 125I-ASD-(Thr28,Ahx31)-CCK-25-33 as a component of Mr approximately 85,000-100,000. The efficiency of the photolabelling was 3-4%. Performing photolysis on [125I-ASD-(Thr28,Ahx31)-CCK-25-33-receptor] complexes solubilized by CHAPS did not affect specificity of the labelling reaction but enhanced its efficiency so that up to 10% of the receptor site population could be cross-linked. Several lectins were tested for their ability to recognize and purify the cholecystokinin receptor denaturated by Nonidet P-40. Wheat germ agglutinin provided the best recovery and purification rate. The receptor was fully adsorbed on immobilized wheat germ agglutinin, while only a fraction was retained on ricin II (28%) and Ulex europaeus (58%), thus suggesting that the receptor is heterogeneously glycosylated. Finally, major labelled receptor fragments were generated by enzymatic digestion. There were: endoproteinase Glu-C ---Mr approximately 34,000; endoproteinase Glu-C/trypsin----Mr approximately 12,000; chymotrypsin/endoproteinase Glu-C----Mr approximately 16,000 and 12,000. The fragment of Mr approximately 34,000 was deglycosylated to a component of Mr approximately 22,000 whereas the other fragments were insensitive to deglycosylation Such results strongly suggest that cholecystokinin binding occurs in a non-glycosylated domain of the cholecystokinin receptor protein. PMID- 1583624 TI - Human hypertension--progress in the last five years. PMID- 1583625 TI - The relationship between urinary cations obtained from the INTERSALT study and cerebrovascular mortality. AB - An epidemiological study on the relationship between 24 hour urinary sodium, potassium, calcium, magnesium and creatinine (Creat), as obtained from the INTERSALT study, and cerebrovascular disease (CVA) mortality in the age standardised group 45-74 years, was conducted using data from 25 countries worldwide. A significant positive relationship was observed by multivariate analysis between cerebrovascular disease mortality and 24 hour urinary Na excretion in men, with Na/K ratio in women and with Na/Creat ratio in all groups. A significant negative correlation was found between the 24 hour urinary magnesium excretion and CVA mortality in men and in men and women averaged, while 24 hour urinary potassium excretion correlated significantly and negatively with CVA mortality in women. No significant relationship between systolic and diastolic blood pressure, 24 hour urinary calcium excretion and BMI with CVA mortality could be established. A log10 transformation revealed a significant positive relationship between Ca/Mg ratio with CVA mortality in men as well as in the group of men and women averaged. A significant negative correlation between CVA mortality and 24 hour creatinine excretion was found. This relationship was stronger in men and could point to a protective effect of protein intake. The findings also point to a direct relationship between dietary cation intake and CVA mortality. PMID- 1583626 TI - Salt intake and stroke: a possible direct effect. AB - We have performed an ecological analysis of the relationship between regional mortality from cerebrovascular disease in western Europe and regional data on urinary sodium excretion, systolic blood pressure and relevant confounding variables. We have used published WHO cerebrovascular disease mortality rates and data provided by the INTERSALT study. Inter-relationships between these variables were investigated by linear regression analysis, with the regression coefficients, weighted for population size. On univariate analysis a significant linear relationship was observed between regional stroke mortality and median 24 hour urinary sodium excretion (coef. = 0.01, t = 3.28, P = 0.008), body mass index (coef. = 0.24, t = 3.21, P = 0.009) and alcohol intake (mls/week, coef. = 1.54, t = 3.99, P = 0.003). The relationship between stroke mortality and systolic blood pressure, though positive, was weaker than that between stroke mortality and sodium excretion and was not significant in this data. The stroke mortality sodium excretion relationship was independent of BMI on multivariate analysis. These data are consistent with the hypothesis that a high intake of salt may increase the risk of stroke, independent of effects on blood pressure. PMID- 1583627 TI - Metabolic cardiovascular risk factors and the renin-aldosterone system in essential hypertension. AB - Impairment of glucose and lipid metabolism is common in hypertensive subjects. In the present study the relationships between indices of lipid and glucose metabolism and the renin-aldosterone system were studied in 37 untreated hypertensive subjects (DBP greater than 95 mmHg). Fasting insulin and the early insulin response at an intravenous glucose tolerance test were both correlated to plasma renin activity (r = 0.48, P less than 0.003 and r = 0.55, P less than 0.002, respectively) while HDL-cholesterol was found to be inversely related to the urinary excretion of aldosterone (r = 0.35, P less than 0.03). These relations were still significant when influences of age, sex, obesity (BMI) and serum creatinine were taken into account in the multiple regression analysis. In conclusion, hyperinsulinaemia and low levels of HDL-cholesterol were found in hypertensive subjects with a high activity of the renin-aldosterone system and might explain the high incidence of cardiovascular diseases found in this group. PMID- 1583628 TI - Does sequential automated measurement improve the estimate of resting blood pressure? AB - Repeated blood pressure measurements made in sequence over short time intervals have been recommended in some studies of antihypertensive drugs, with the aim of improving the estimate of 'true' resting BP values. In order to examine this claim, the variance of four sequential automatic recordings of BP and heart rate was evaluated in 66 subjects. The oscillometric Nippon Colin BP-103N sphygmomanometer has been previously shown by our group to give accurate and consistent measurements of BP. The means and medians of three sequential readings, by significantly decreasing the variability, were found to be superior to single measurements. The recorded mean arterial pressures were significantly higher than those calculated according to the current formula, on average by 3.6 mmHg, being situated between one third and one half of the distance between the systolic and diastolic pressures. The Page's rank test revealed that the first measurements were not uniformly the highest ones. Since the variability of the first to third BP values did not differ, medians of the three sequential recordings made at one minute intervals can be recommended as a standard BP characteristic. PMID- 1583629 TI - Doppler echocardiographic assessment of filling and emptying parameters and ambulatory blood pressure measurements in normotensives and hypertensives. AB - To evaluate the relationship between office and ambulatory BP measurements and filling and emptying parameters, 15 hypertensive and 15 control subjects underwent both 24 hour ambulatory BP monitoring and Doppler echocardiography. No patient received antihypertensive medication for 3-4 weeks, had echocardiographic left ventricular hypertrophy (greater than or equal to 12 mm) or a diastolic BP greater than 100 mm Hg. The time from R wave on the electrocardiogram to onset of ejection was prolonged in hypertensives (P less than 0.05). There were no differences between the hypertensives and normotensives for diastolic filling abnormalities. Finally, neither office nor ambulatory BP correlated with either Doppler filling or emptying parameters. PMID- 1583630 TI - Tracking of blood pressure and anthropometric measures in Nigerian children. AB - Persistence in ranks (tracking) for blood pressure and anthropometric measures over a one year period was examined in 208 Nigerian children (age 6-17 years). Systolic blood pressure tracked better than diastolic blood pressure (r = 0.52 to 0.72) and r = 0.25 to 0.55, respectively). For systolic blood pressure, 56.5% 70.6% of the Nigerian children remained in the top tertile after one year compared with 45.5%-69.2% for diastolic blood pressure. Weight showed the strongest correlation over the one year period (r = 0.88 to 0.97), whereas skinfolds demonstrated the weakest association (r = 0.54 to 0.82). The association between anthropometric measures at baseline and blood pressure one year later revealed for both males and females that height and weight were positively and significantly correlated with blood pressure. PMID- 1583631 TI - Blood pressure and mortality: an epidemiological survey with 10 years follow-up. AB - The Copenhagen City Heart Study is a prospective ischaemic heart disease population study designed to evaluate incidence of, and risk factors for, ischaemic heart disease. A random population sample of approximately 20,000 men and women was invited to participate in a health survey, which was carried out in 1976-78. The participation rate was 74%. Systolic (SBP) and diastolic blood pressure (DBP) was measured with the London School of Hygiene sphygmomanometer after 5 minutes in the sitting position. Risk factors were assessed by a questionnaire and non-fasting plasma cholesterol was measured. Information about subsequent death and causes of death was obtained from the Danish Death Register. Follow-up was virtually complete over an observation time of 10 years. Analysis of the independent effect of SBP and DBP measured at entry on the 10 year total and cause-specific mortality was performed using the Cox regression model. Antihypertensive medication and/or diuretic therapy, physical activity during leisure time, economic and educational status, tobacco and alcohol consumption, diabetes mellitus, body mass index, plasma cholesterol levels, age and sex were entered as confounders. Total mortality was increased only in the higher quintiles of SBP. Concerning ischaemic heart disease mortality and cerebrovascular mortality, the risk increased in a graded manner with increasing quintile of SBP and DBP. With regard to cancer mortality, a U-shaped association was observed between quintile of SBP (and DBP) and death rate. With advancing age, the predictive power of SBP on total and cause-specific mortality changed, especially in males, as a pronounced U-shape of the association between BP and mortality appeared. The reasons for this are discussed. The relative risk in subjects receiving antihypertensive medication was 1.7 (CL 1.5-2.0) regarding total mortality, 2.0 (CL 1.5-2.7) regarding ischaemic heart disease mortality, 0.8 (CL 0.5-1.4) regarding cerebrovascular mortality, and 1.3 (CL 1.0-1.7) regarding cancer mortality. This finding is in agreement with clinical trials experiences, and may have an impact on management of high blood pressure. PMID- 1583632 TI - Maternal and umbilical venous levels of endothelin in women with pre-eclampsia. AB - Endothelin is a recently discovered, potent vasoconstrictive peptide. To investigate its involvement in pre-eclampsia, we measured its concentration in the plasma of 10 healthy non-pregnant women, 19 healthy pregnant women in early pregnancy, 26 healthy pregnant women in the third trimester, 18 women with pre eclampsia in the third trimester and 6 women with pre-eclampsia in the postpartum period. In addition, the concentration of endothelin in umbilical venous plasma was measured in 7 healthy pregnant women and in 4 with pre-eclampsia. A sandwich enzyme immunoassay for endothelin-1[1-21] was used. The plasma concentration of endothelin in pre-eclampsia significantly exceeded that of the healthy pregnant women during the third trimester. In pre-eclampsia this elevated level of plasma endothelin normalised with the fall in blood pressure 7 days postpartum. The level of endothelin in the umbilical vein was 6 to 8 times higher than that in the cubital vein both in the healthy pregnant women and in those with pre eclampsia, but there was no significant difference in the umbilical venous plasma concentration of endothelin between those two groups. These observations suggest that the synthesis of endothelin may be increased in pre-eclampsia and that this increase may play a role in the elevation of peripheral vascular resistance and the production of peripheral ischaemic damage. Damage to the endothelial cells may then stimulate the synthesis of endothelin to initiate a vicious cycle. PMID- 1583633 TI - Coping and blood pressure. AB - The relationship between psychological coping strategies and BP was analysed in a group of 158 southern Italian men and women aged 20-59, randomly selected from an epidemiological study on coronary heart disease risk factors. Coping strategies were evaluated by use of a self-administered questionnaire (Jalowiec Coping Scale) listing 40 frequently used strategies. Factor analysis revealed the reported use of 5 different coping strategies. Males, on average, reported seeking less external support than females. In both sexes, increased years of education were associated with increased use of solution-oriented coping strategies and decreased use of resignation and sympathy seeking. After adjustment for age, alcohol use, body mass index, education and smoking, increased use of resignation was associated with lowered BP in both sexes. Emotional coping was inversely related to BP in males, but not in females. The search for external support was associated with a higher BP only in males. These data provide some evidence to suggest that psychological coping modalities are related to blood pressure. PMID- 1583634 TI - Cytosolic free calcium concentration in platelets in patients with renovascular hypertension and primary aldosteronism. AB - To investigate the role of cytosolic free calcium, [Ca2+]i, in secondary hypertension, the levels in platelets from 14 secondary hypertensives (7 renovascular hypertension, 7 primary aldosteronism) were compared with those from 21 essential hypertensives and 15 normotensives by means of the fluorescent indicator, quin-2. The mean BP was significantly higher in both the secondary hypertensives and essential hypertensives (122 +/- 8 and 124 +/- 12 mmHg) than in the normotensives (89 +/- 10 mmHg). Cytosolic free calcium in platelets was significantly higher in the essential hypertensives, but not in the secondary hypertensives, compared with the normotensives (182 +/- 34, 141 +/- 17, 138 +/- 15 nM respectively). There was no significant difference in platelet [Ca2+]i between renovascular hypertension and aldosteronism (142 +/- 19 versus 139 +/- 16 nM). There was no correlation between platelet [Ca2+]i and plasma renin activity, plasma aldosterone concentration or plasma noradrenaline concentration in the three groups. Thus, the increase in platelet [Ca2+]i seen in essential hypertension was not found in patients with secondary hypertension. Our results suggest that the cytosolic calcium handling of secondary hypertensive patients with renal artery stenosis or primary aldosteronism differs from that of essential hypertensives. PMID- 1583635 TI - Conn's syndrome can cause malignant hypertension. AB - We present a case in which a patient, having already sustained an episode of malignant hypertension, was subsequently found to have an underlying Conn's adenoma. Ablation of the adenoma improved control of her hypertension. When a second adenoma developed in her remaining adrenal gland, control of her hypertension deteriorated. PMID- 1583636 TI - Impairment of baroreceptor reflex in patients with phaeochromocytoma. AB - We examined the baroreceptor reflex sensitivity (BRS) in two patients with adrenal phaeochromocytoma because of their wide BP fluctuations. These patients showed greatly reduced values for BRS, which returned to normal with marked improvements of BP fluctuations soon after the removal of phaeochromocytoma. In these patients, circulating blood volume was normal and episodic rises in BP occurred without detectable increases in plasma catecholamines. From these observations, a marked impairment of baroreceptor function is considered to be one of the determinants for the wide BP fluctuation in patients with phaeochromocytoma. PMID- 1583637 TI - Effects of crossover application of sulindac and azelastine on enalapril-induced cough. PMID- 1583638 TI - Beckwith-Wiedemann syndrome: a demonstration of the mechanisms responsible for the excess of transmitting females. AB - Beckwith-Wiedemann syndrome (BWS) is often associated with embryonal tumours (nephroblastoma, adrenocortical carcinoma, hepatoblastoma, and rhabdomyosarcoma). Several pedigrees have been reported strongly suggesting autosomal dominant inheritance and an excess of transmitting females was noticed in these families. We confirmed this excess using 19 published pedigrees and showed that this excess was for two reasons: first, reduced fecundity in affected males compared to females in a ratio of 1:4.6, and, second, a smaller risk of being affected in a ratio of 1:3 for subjects having inherited the gene from their father. These latter findings suggest genomic imprinting. Furthermore, considering these results together with other observations, such as the parental origin of the 15p15.5 duplication and the existence of uniparental disomy in some sporadic cases, we propose that overgrowth in BWS patients and malignant proliferation in associated tumours reflect an imbalance between paternal and maternal alleles. PMID- 1583639 TI - Evidence for paternal imprinting in familial Beckwith-Wiedemann syndrome. AB - A previously unreported family in which seven members in two generations have Beckwith-Wiedemann syndrome (BWS) is documented. Paternal imprinting of the gene responsible for BWS is involved as the mechanism responsible for the aberrant inheritance pattern in this kindred. A review of published reports showed 27 previously published pedigrees with two or more affected subjects with BWS. Paternal imprinting would explain the non-mendelian inheritance of BWS in all but four kindreds. The latter families are examined in more detail and in only one example is the evidence against imprinting totally unexplained. PMID- 1583641 TI - Screening of microdeletions of chromosome 20 in patients with Alagille syndrome. AB - We report a cytogenetic and molecular study of a series of patients with Alagille syndrome. All 14 patients were studied with high resolution banding techniques and eight of them were also analysed with non-radioactive in situ hybridisation of the cosmid probe D20S6. Seven of these eight patients were also studied for allelic losses at the D20S6 locus. No microdeletion of chromosome 20 was found in this series. PMID- 1583640 TI - Sex reversal in a child with a 46,X,Yp+ karyotype: support for the existence of a gene(s), located in distal Xp, involved in testis formation. AB - We report on a sex reversed Japanese child with a 46,X,Yp+ karyotype, minor dysmorphic features, and no testicular development. The Yp+ chromosome was derived by translocation of an Xp fragment (Xp21-Xp22.3) to Yp11.3. This has resulted in deletion of distal part of the Y chromosome pseudoautosomal region (DXYS15-telomere) and duplication of the X specific region (DXS84-PABX) and proximal part of the pseudoautosomal region (MIC2-DXYS17). No deletion of the Y specific region was detected nor was any mutation found in SRY. Cytogenetic analysis suggests that the proximal part of the Xp fragment is the most distal part of the short arm of the Yp+ chromosome (Xp21----Xp 22.3::Yp11.3----Yqter). No chromosomal mosaicism was detected. These results are similar to previous reports of sex reversal in four subjects with a 46,Y,Xp+ karyotype. We conclude that the sex reversal is a direct, or indirect, consequence of having two active copies of the distal part of Xp and may indicate the presence of a gene(s) which acts in the testis determination or differentiation pathway. PMID- 1583642 TI - Confirmation of genetic linkage between atopic IgE responses and chromosome 11q13. AB - Genetic linkage between atopic IgE responses and chromosome 11q13 (D11S97) has been previously reported in a limited number of extended families. Difficulties of phenotyping in the older family members, poor family structure in some families, and genetic heterogeneity were proposed as possible explanations for the variability in lod scores. To test this finding a second linkage study of 64 young nuclear families was undertaken and gave a two point lod score of 3.8 at theta = 0.07 (assuming theta m = theta f). A test of genetic heterogeneity in the nuclear families shows that atopic IgE responses are linked to this locus in 60 to 100% of families (approximate 95% confidence limits). PMID- 1583643 TI - Genetic and clinical studies in autosomal dominant polycystic kidney disease type 1 (ADPKD1). AB - Thirteen Spanish families with autosomal dominant polycystic kidney disease were studied. In one family the disease did not segregate with polymorphic markers around the PKD1 locus. All subjects over the age of 30 years carrying a mutation at the PKD1 locus showed renal ultrasonographic cysts, but 40% of carriers of the PKD1 mutation younger than 30 years did not have renal cysts. Hypertension was found to be more frequent in those with renal cysts. Recombinants between 16p polymorphic loci and the PKD1 locus are described. PMID- 1583644 TI - Evidence for linkage disequilibrium between D16S94 and the adult onset polycystic kidney disease (PKD1) gene. PMID- 1583645 TI - Campomelic dysplasia associated with a de novo 2q;17q reciprocal translocation. AB - A phenotypically female fetus with campomelic dysplasia and a de novo reciprocal translocation, 46,XY,t(2;17) (q35;q23-24), is presented. This is the second case of campomelic dysplasia in which a rearrangement involving the long arm of chromosome 17 has been identified, indicating that this is likely to be the site of the campomelic dysplasia locus. PMID- 1583646 TI - A complex chromosome rearrangement with 10 breakpoints: tentative assignment of the locus for Williams syndrome to 4q33----q35.1. AB - An unbalanced complex chromosome rearrangement with 10 breakpoints resulting in four derivative chromosomes (1, 2, 4, and 11) was found in a girl with severe phenotypic abnormalities, many of which are characteristic of Williams syndrome. The patient was monosomic for the region 4q33----q35.1 and thus the mapping of the syndrome could tentatively be restricted to this region. PMID- 1583647 TI - Evidence that Rieger syndrome maps to 4q25 or 4q27. AB - We report a baby with the features of Rieger syndrome and a de novo interstitial deletion of 4q which includes band 4q26 and an adjoining GTL light band, either q25 or q27. Rieger syndrome is provisionally mapped to 4q23----q27 but band 4q26 has been excluded as a possible site, suggesting that Rieger syndrome must map to a band, either 4q25 or 4q27, adjoining 4q26. PMID- 1583648 TI - Interstitial deletion of the distal long arm of chromosome 4. AB - We report the first case of an interstitial deletion of the distal long arm of chromosome 4 (q31.22----q34.2). The major clinical features are described and compared to those of other published reports of del 4q, mainly those sharing a common deleted segment with the present case (both interstitial and terminal). This comparison suggests that the characteristic phenotype attributed to terminal deletions of 4q31----qter probably mainly results from loss of the segment q31--- q33-34. PMID- 1583649 TI - The orocraniodigital syndrome of Juberg and Hayward. AB - We report three new isolated cases of orocraniodigital syndrome (Juberg-Hayward syndrome). The main clinical features of this unusual birth defect (six patients from three families described so far) are cleft lip/palate, hypertelorism, bowed and upward slanting eyebrows, thumb hypo/aplasia or proximal/distal thumb displacement, luxation of the radial head, elbow restriction, minor vertebral and rib anomalies, and horseshoe kidneys. New features observed in our patients are severe mental impairment (not correlated with the severity of the malformations), anterior anal displacement, and ptosis. Recessive inheritance is likely, but autosomal dominant inheritance cannot yet be totally ruled out; therefore, genetic counselling of parents of an affected child and of affected patients themselves must be cautious. PMID- 1583650 TI - The Baller-Gerold syndrome. AB - A case of severe craniosynostosis-radial aplasia (Baller-Gerold) syndrome is described in a newborn male, following a pregnancy complicated by polyhydramnios and intrauterine growth retardation. Death occurred after two hours owing to a prolonged apnoeic spell. Extensive agenesis of the frontal and parietal bones, resulting in a very large fontanelle, in addition to coronal bilateral craniosynostosis was observed at necropsy. There was also bilateral radial agenesis, oligodactyly of the hands and feet, a midline facial angioma, and a scrotally positioned anus, all of which have been described in some of the 10 previously reported cases. Microcephaly, erythroblastosis of the liver, and pancreatic islet cell hypertrophy were also noted. PMID- 1583651 TI - Fragile X syndrome: as common as first thought? PMID- 1583652 TI - Hypoglossia-hypodactyly syndrome with hydrocephalus. PMID- 1583653 TI - Cone and cone-rod dystrophies. PMID- 1583654 TI - X linked progressive cone dystrophy with specific attention to carrier detection. AB - We investigated 111 members of a five generation family with X linked cone dystrophy. The patients showed the characteristic picture of cone dystrophy. Routine ophthalmological examination of the carrier women showed no abnormalities. However, with detailed colour vision testing we were able to detect 87% of all obligate carriers. PMID- 1583655 TI - Late onset dominant cone dystrophy with early blue cone involvement. AB - A dominant cone dystrophy spanning seven generations was found in a pedigree from the Netherlands. The onset of the decline of visual acuity started after the age of 20, while a near complete absence of blue cone function (a so-called tritan defect) already existed before the presence of any ophthalmological abnormalities. PMID- 1583656 TI - Reverse chromosome painting: a method for the rapid analysis of aberrant chromosomes in clinical cytogenetics. AB - We describe a method, termed reverse chromosome painting, which allows the rapid analysis of the content and breakpoints of aberrant chromosomes. The method involves the sorting of small numbers of the aberrant chromosome from short term blood culture preparations or cell lines by using bivariate flow karyotype analysis. The sorted chromosomes are amplified and biotin labelled enzymatically using a degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR), the product annealed to metaphase spreads from normal subjects, and hybridisation detected using fluorescence in situ hybridisation (FISH). We show the usefulness of this method for routine clinical cytogenetics by the analysis of cases involving an insertion, a deletion, a translocation, and two cases of a chromosome with additional material of unknown origin. The method has particular application for the rapid resolution of the origin of de novo unbalanced chromosome duplications. PMID- 1583657 TI - Prenatal cystic fibrosis carrier testing: designing an information leaflet to meet the specific needs of the target population. AB - A questionnaire was given to 180 patients in an antenatal clinic, who were eligible to enter a pilot trial of cystic fibrosis (CF) carrier testing, seeking their views on the information leaflet inviting them to participate; 161 patients (89%) entered the trial and 145 patients (81%) responded to the questionnaire, including 10 who did not enter the trial. Ninety-six percent of these found the leaflet easy to understand, and 97% of those partners who read the leaflet also found it easy to understand. Fifteen percent of patients thought the leaflet should give additional information. Most (92%) had heard of CF before reading the leaflet, television being the most common source of information. Although avoiding the birth of a child with CF was the reason most patients gave for wishing to be screened, almost as many were interested to know their carrier status. The decision to accept or decline testing was taken in conjunction with their partner by 63% of women. Of those who were screened, 59% stated that taking the test made them feel reassured, while 38% felt slightly apprehensive. It was concluded that, with a number of minor amendments, the leaflet met the specific needs of the target patient population. PMID- 1583658 TI - Principles and practicalities of carrier screening: attitudes of recent parents. AB - Population carrier screening for cystic fibrosis could soon be a reality, but we know very little about people's attitudes towards genetic disease in general or cystic fibrosis in particular. This paper reports a study which aimed to investigate some of these attitudes and also to explore feelings about CF carrier screening given its practical limitations. The results are discussed in the context of earlier studies which have not raised these practical issues. PMID- 1583659 TI - Ectodermal dysplasia with blindness in sibs on the island of Rodrigues. AB - A brother and sister from the island of Rodrigues had mental retardation, blindness owing to severe ocular malformations, short stature, dysmorphic facial features, hypotrichosis, and dental abnormalities. It is likely that they have a hitherto unrecognised autosomal recessive ectodermal dysplasia syndrome. PMID- 1583660 TI - Oculoauriculovertebral spectrum and cerebral anomalies. AB - We report on three Dutch children with a clinical diagnosis of oculoauriculovertebral spectrum (OAVS) and hydrocephalus. The clinical features are compared to 15 published cases of OAVS and hydrocephalus. Several other cerebral abnormalities were present in the whole group. About half of the cases had cleft lip/palate, anophthalmia/microphthalmia, or a cardiac defect. Mental retardation was found in five of the surviving 11 patients and early death occurred in one-third. We compared the cases with OAVS and hydrocephalus with published reports of OAVS and other cerebral anomalies and found no significant clinical differences. However, the clinical characteristics were clearly more severely expressed than generally found in patients with OAVS. Children with OAVS and more severe clinical features, especially anophthalmia/microphthalmia and cleft lip/palate, seem to be at an increased risk for cerebral malformations and for mental retardation. PMID- 1583661 TI - Weaver syndrome. PMID- 1583662 TI - Monosomy 10qter: a new case. AB - A new case of terminal deletion 10q26-qter is described. The phenotypic features are compatible with those of the previously reported cases. Deafness is reported for the first time. PMID- 1583663 TI - Tandem duplication of the terminal band of the long arm of chromosome 7 (dir dup (7)(q36----qter)). AB - We report on a new case of a single band duplication of the long arm of chromosome 7, dir dup (7)(q36----qter). The major manifestations are developmental delay (particularly speech), frontal bossing, macrocrania, and constant drooling. When compared with other cases involving a 7q duplication of various segments, our patient has a few minor anomalies. This case illustrates the genotype/phenotype correlation in a child with a single band duplication which has resulted in duplication of 7q36----qter. A tabulation of reported cases with duplication of various segments of 7q is provided, which may serve as an aid for clinicians. PMID- 1583664 TI - Brachydactyly type C associated with shortening of the hallux. AB - A four generation autosomal dominant pedigree of brachydactyly type C is presented with its radiological features. The hands and feet were similarly affected. All the subjects showing these changes had shortening of the big toes and, in addition, had cupped ears. PMID- 1583665 TI - Atypical case of Aarskog syndrome. PMID- 1583666 TI - A de novo insertion, detected prenatally, with normal phenotype. PMID- 1583667 TI - X linked alpha thalassaemia/mental retardation (ATR-X) syndrome. PMID- 1583668 TI - 49,XXXXY syndrome: behavioural and developmental profiles. PMID- 1583669 TI - The double disector: unbiased stereological estimation of the number of particles inside other particles. AB - A double-disector method for obtaining estimates of the number of particles inside other particles, illustrated by an estimation of the average cell number in a glomerulus, has been developed. The method is suitable for paraffin-embedded tissue because it does not require knowledge about the section thickness. Most importantly, the estimate is absolutely unaffected by tissue shrinkage. The average number of cells in a human glomerulus is 2850 whereas in rats it is 580. PMID- 1583670 TI - The efficient and unbiased estimation of nuclear size variability using the 'selector'. AB - The selector was used to make an unbiased estimation of nuclear size variability in one benign naevocellular skin tumour and one cutaneous malignant melanoma. The results showed that the estimates obtained using the selector were comparable to those obtained using the more time consuming Cavalieri-disector approach. Employing 'optical sections,' the selector was found to be between five and ten times more efficient than the Cavalieri-disector method when using physical sections. PMID- 1583671 TI - Social health and the forgiving heart: the Type B story. AB - The evolution of the Type A hypothesis is well documented. The protective corresponding Type B construct has not evolved similarly. Using experiences from Friedman's Recurrent Coronary Prevention Project, on a speculative basis, four neglected protective processes are examined: uniqueness/self-esteem/autonomy, forgiveness, sociability, and "causal" wisdom attributions. A more integrative set of questions is proposed to expand our knowledge of adaptive fitness and success. PMID- 1583672 TI - Psychological adjustment and perceived social support in children with congenital/acquired limb deficiencies. AB - The negative impact on psychological adjustment from the chronic strain of living with limb deficiencies appears to be mediated by perceived social support. A multifactorial investigation was conducted to identify empirically psychological adjustment correlates of perceived social support in 49 children with congenital/acquired limb deficiencies. A multiplicity of adjustment factors (depression, trait anxiety, self-esteem) was variously related to perceived parent, teacher, classmate, and friend social support. Hierarchical multiple regression analyses provide initial evidence of the potentially powerful effects of the social environment of the school setting, with perceived classmate social support the only significant predictor variable across depressive symptomatology, trait anxiety, and general self-esteem. The results are discussed as the first step in identifying the potential correlates of multiple perceived social support domains, which may provide empirical guidance for future intervention studies designed to modify adjustment factors in chronically ill and handicapped children. PMID- 1583673 TI - An effective treatment for functional urinary incoordination. AB - Twenty women diagnosed with functional urinary incoordination were randomly assigned to one of two treatment groups: biofeedback or progressive muscle relaxation. Ten subjects who were placed on a waiting list prior to treatment allocation served as a comparison group. The biofeedback intervention focused specifically on retraining of pelvic floor musculature (PFM). Patients were assessed pretreatment, posttreatment, and at 2-month follow-up. Outcome measures included self-reported symptomatology, psychological functioning, psychophysiological assessment of the PFM, and urologist ratings of problem severity and treatment efficacy. Both treatment approaches proved effective in improving symptomatology and psychological state. Subjects on the waiting list demonstrated no change in urological difficulties. No differences were found between the two treatment groups on any of the outcome measures. Theoretical and practical implications of the results are discussed. PMID- 1583674 TI - The role of efficacy cognitions in the prediction of exercise behavior in middle aged adults. AB - The present study adopted a social cognitive framework to examine the role played by perceptions of personal efficacy in adherence to exercise behavior in sedentary middle-aged adults. Subjects were followed for 5 months in order to study the process of exercise as it moved through the adoption to maintenance stage of the behavior. Participation rates paralleled those reported elsewhere in the literature. Path analytic techniques examined the role over time of efficacy, perceptual, and behavioral indicators of frequency and intensity of exercise. Self-efficacy cognitions were shown to predict adoption of exercise behavior but previous behavior proved to be the strongest predictor of subsequent exercise participation. Results are discussed in terms of examining process versus static design models in exercise and physical activity research. Implications for future research and health promotion are suggested. PMID- 1583675 TI - Electromyographic and affective responses of episodic tension-type headache patients and headache-free controls during stressful task performance. AB - Thirty-four subjects meeting diagnostic criteria for episodic tension-type headache and 42 who rarely experienced headaches participated in two laboratory sessions in which cephalic electromyographic (EMG) activity, electrodermal activity, heart rate, and finger temperature were recorded. Subjects performed relaxation, choice reaction time, psychomotor tracking, voluntary muscle contraction, and cold pressor tasks. Headache subjects showed significantly greater EMG activity than controls during baseline and stressful task performance. During relaxation, both groups reduced EMG activity from baseline levels, and there was no significant difference in EMG level between the groups during relaxation. Headache subjects reported higher levels of subjective anxiety, depression, anger, and stress than controls. Headache subjects also reported higher levels of pain than controls, and headache subjects reported greater pain during stressful task performance relative to baseline and recovery periods. PMID- 1583676 TI - Symptoms of illness in late adulthood are related to childhood social deprivation and misfortune in men but not in women. AB - Experiencing adverse life events during childhood may increase vulnerability to physical illnesses and psychological disorders during adulthood. We developed an Early Life Events Questionnaire (ELEQ) with 12 scales and administered it to 92 relatively healthy elderly individuals (29 men and 63 women). A canonical correlation analysis of the 12 ELEQ scales and physical and psychological symptoms revealed a significant canonical correlation. The results indicate that those who grew up in a family with a harsh climate and whose affiliation needs were not met tended to have more psychological and physical symptoms in old age. Regression analysis revealed that, in men, early life events accounted for 42% of the variance in physical symptoms and 39% in psychological symptoms. No significant relationship, however, was found between ELEQ scales and health outcomes in women. These results suggest that women may be less vulnerable than men to the adverse health consequences of childhood deprivation and other misfortunes. PMID- 1583677 TI - The relationship of dispositional optimism, daily life stress, and domestic environment to coping methods used by cancer patients. AB - The relationship of dispositional optimism, daily life stress, and domestic environment to two types of coping methods was examined in a group of 94 cancer patients. As expected, dispositional optimism and domestic environment made significant contributions to the prediction of avoidance coping. Dispositional optimism contributed significantly to the prediction of active-behavioral coping. Specifically, a significant positive relationship was obtained between active behavioral coping and optimism. A significant positive relationship also was found between avoidance coping and both daily stress and domestic environment. Avoidance coping was negatively related to dispositional optimism. In multivariate analyses, gender and disease-related variables did not make significant contributions to the prediction of coping method. Suggestions for future research were made. PMID- 1583678 TI - Age-related changes in behavioral components in relation to changes in global Type A behavior. AB - The current study is one of a series of studies undertaken to investigate long term changes of the Type A behavior pattern (TABP) in surviving subjects of the Western Collaborative Group Study. Behavioral components were scored for 565 Structured Interviews (SI) of returning subjects using a recently developed methodology. Scores were compared with component ratings from the 1960-1961 intake interviews to isolate specific elements of change and evaluate their magnitude in relation to changes in global TABP. Test-retest correlations for seven behavioral components of the SI support the notion of moderate stability ranging in value from .29 to .55. Significant mean changes in component scores were observed for Type A Content, Exactingness, Competitiveness, and Hostility. Changes in Competitiveness and Hostility were Type A dependent, showing reliable increases in Type A subjects but not in Type B subjects. The observed changes in Hostility, Competitiveness, and Exactingness support the overall change in the Type A direction observed in previous analyses of these data. PMID- 1583679 TI - Binge eating among the obese: a descriptive study. AB - Nineteen obese females applying for treatment for binge eating were administered a semistructured interview assessing the presence or absence of food restrictions, thoughts, feelings and physical sensations associated with binges, typical precipitants to binges, and factors identified as useful in avoiding binge eating. Both negative mood and abstinence violations emerged as important precipitants. The results also suggested that these precipitants constitute separate, independent pathways to binge eating. Implications of these findings with respect to restraint theory are discussed. PMID- 1583680 TI - Coping and cognitive factors in adaptation to in vitro fertilization failure. AB - Characteristics were identified that predict adaptation following an unsuccessful attempt at in vitro fertilization (IVF). Forty-one women and their husbands were interviewed and administered questionnaires prior to IVF and 2 weeks after notice of a positive or negative pregnancy test. Of the 36 couples who failed to conceive as a result of IVF, 6 of the women studied developed clinical depressive symptoms. Those women who reported poorest adaptation to IVF failure were more likely to have reported depressive symptoms prior to IVF, were more likely to have reported feeling a general loss of control over their lives as a result of infertility, tended to use escape as a coping strategy, and reported having felt some responsibility for their IVF failure. Dispositional optimism, as well as a sense of being partially responsible for the infertility, was protective of distress following IVF failure. PMID- 1583681 TI - The relation between stress and disease activity in rheumatoid arthritis. AB - This study investigated the relation between stress and current disease activity in rheumatoid arthritis (RA). During a routine clinic appointment, subjects were given ratings of global disease status by their physicians and completed self report measures of major stress and minor stress. In addition, each subject's erythrocyte sedimentation rate was taken. After controlling for disease severity and major stress, minor stress accounted for a significant amount of the variance in inflammation level. These results suggest that minor stress is associated with current disease activity in RA. PMID- 1583682 TI - The Survey of Recent Life Experiences: a decontaminated Hassles Scale for adults. AB - A new decontaminated hassles measure for adults, the Survey of Recent Life Experiences, was developed and validated. An initial pool of 92 items was administered to 100 subjects along with the Perceived Stress Scale. Fifty-one items were selected, based on significant correlations with the latter scale. The alpha reliability of the resultant final form of the Survey of Recent Life Experiences and its correlation with perceived stress were both high. In a separate cross-replication sample of 136 adults, the alpha reliability of the Survey and its correlation against the Perceived Stress Scale remained acceptably high. Moreover, separate-sex analyses supported the reliability and validity of the Survey of Recent Life Experiences across gender. Factor analysis of the Survey yielded six interpretable factors. Intercorrelations among subscales based on these factors were generally modest, suggesting that the scale is relatively free from contamination by psychological distress. PMID- 1583683 TI - Nuclear magnetic resonance and circular dichroism studies of a triple-helical peptide with a glycine substitution. AB - The triple-helical conformation has the stringent amino acid sequence constraint that every third residue must be a glycine, (X-Y-Gly)n. We use nuclear magnetic resonance and circular dichroism to quantify the consequences of a substitution in the glycine position of a triple-helical peptide, and to enhance our understanding of interactions in this basic structural motif. A 30-residue peptide with a Gly----Ala change forms a stable trimer at a folding rate somewhat less than that of the unsubstituted peptide, and the substitution results in a marked decrease in thermal stability and a conformational perturbation of about 30% of the triple-helical structure. Two models were generated for this peptide, one with the alanine residues packed inside the triple helix and one with a looping out of the chain at the substitution site. Studies on the Gly----Ala peptide are useful in understanding connective tissue diseases which result from the substitution of one glycine residue in the triple-helix of fibrillar collagens. PMID- 1583684 TI - Crystal and molecular structure of the bovine alpha-chymotrypsin-eglin c complex at 2.0 A resolution. AB - The crystal structure of the complex between bovine alpha-chymotrypsin and the leech (Hirudo medicinalis) protein proteinase inhibitor eglin c has been refined at 2.0 A resolution to a crystallographic R-factor of 0.167. The structure of the complex includes 2290 protein and 143 solvent atoms. Eglin c is bound to the cognate enzyme through interactions involving 11 residues of the inhibitor (sites P5-P4' in the reactive site loop, P10' and P23') and 17 residues from chymotrypsin. Binding of eglin c to the enzyme causes a contained hinge-bending movement around residues P4 and P4' of the inhibitor. The tertiary structure of chymotrypsin is little affected, with the exception of the 10-13 region, where an ordered structure for the polypeptide chain is observed. The overall binding mode is consistent with those found in other serine proteinase-protein-inhibitor complexes, including those from different inhibition families. Contained, but significant differences are observed in the establishment of intramolecular hydrogen bonds and polar interactions stabilizing the structure of the intact inhibitor, if the structure of eglin c in its complex with chymotrypsin is compared with that of other eglin c-serine proteinase complexes. PMID- 1583685 TI - Characterization of the arginine repressor from Salmonella typhimurium and its interactions with the carAB operator. AB - Primer extension experiments showed that the argR gene, encoding the arginine repressor in Salmonella typhimurium, is transcribed from a single promoter that is negatively regulated by arginine. A repressor overproducing strain was constructed and the repressor was purified to homogeneity. Gel filtration, sedimentation and cross-linking studies established that the native repressor is a hexamer of identical 17,000 Mr subunits. Gel retardation experiments indicate that the apparent dissociation constant for repressor/carAB operator is 6 x 10( 12) M. These experiments showed that arginine is essential for binding of the repressor to the DNA and that pyrimidine nucleotides have no significant effect on this binding. These results indicate that the effect of pyrimidines on expression of the arginine sensitive "downstream" carAB promoter is not directly mediated by the arginine repressor. These experiments also suggest that a single hexamer binds to the carAB operator, which carries two previously defined "ARG box" sequences that characterize operators for arg genes. Gel retardation experiments with DNA fragments carrying the individual ARG boxes showed that both boxes are required for effective binding of the hexameric repressor to the operator, indicating that the ARG boxes comprise a single binding site for the repressor. Analysis of the potential secondary structure of the arginine repressor does not reveal any of the recognizable structural motifs common to a number of DNA-binding proteins. A combination of DNase I, premethylation interference, depurination and hydroxyl radical footprinting techniques were employed to characterize the interactions of the repressor with the carAB operator, with the results suggesting that the repressor predominantly interacts with A.T residues in this region. Comparative DNA sequence analysis of the known arginine operators of enteric bacteria further indicates that the specificity of interaction may be based more on the precise distance between two defined A.T rich regions rather than on the specific nucleotide sequence. PMID- 1583686 TI - Cubic phases of lipid-containing systems. The structure of phase Q223 (space group Pm3n). An X-ray scattering study. AB - The hexagonal (H) and the cubic (Q223) phases of the systems dodecyltrimethylammonium chloride-water and palmitoyllysophosphatidy choline water have been studied by X-ray scattering techniques. The signs of the reflections of phase H were determined by a systematic study as a function of the water content, those of phase Q223 were assessed using a pattern recognition approach based upon the axiom that the histograms of the electron density maps of phases Q223 and H, extrapolated to the same concentration and properly normalized in scale and shape, are very similar to each other. In the case of phase Q223, all the sign combinations (the phi-sets) compatible with the observed reflections were generated, and each of the corresponding histograms was compared with the histogram of the map of phase H. One novelty of this work is the use of a highly sensitive criterion to estimate the similarity of the histograms, namely the distance in the six-dimensional space of the moments [mean value of (delta rho)n]1/n, for 3 greater than or equal to n greater than or equal to 8. In the two systems, the use of this criterion has led to the unambiguous choice of one electron density map. The maps show that the structure of phase Q223 consists of disjointed micelles (of type I), belonging to two different classes: those of one class are quasi-spherical in shape and are centered at the points a, those of the other class are disc-shaped and are centred at the points c. The results of this work rule out a structure formed by a cage-like distribution of rods enclosing a set of quasi-spherical micelles and is consistent with previous proposals. This is the second example, after that of phase Q227, of a micellar cubic phases in lipid-containing systems; all the known examples of phase Q223 are of type I, those of phase Q227 of type II. PMID- 1583687 TI - Isoform purification of gastric lipases. Towards crystallization. AB - Several isoforms of rabbit and human gastric lipases have been purified. These isoforms have the same apparent molecular weight (Mr approximately 50,000), but very different isoelectric points. Some of these isoforms were purified: pI 7.2 and 6.5 in the case of rabbit gastric lipase; and pI 7.4 and 7.2 in that of human gastric lipase. All the purified isoforms were found to have the same specific lipase activity (around 1200 units per mg of protein, measured on tributyrin as substrate). The isoforms of dog gastric lipase are more closely related, and could not be separated. Partial enzymatic deglycosylation of human gastric lipase reduced the apparent molecular weight from Mr approximately 50,000 to Mr approximately 43,000 and induced a change in the isoelectrofocusing pattern and the emergence of a new isoform (pI 7.3). It is concluded that the charge heterogeneity of gastric lipases is at least partly due to the glycan moiety of the molecule, which amounts to approximately 14% of the total molecular weight. Several crystallization trials on purified native preparations of rabbit and human gastric lipases were unsuccessful, whereas crystals were obtained from native dog gastric lipase and all the purified isoforms of rabbit and human gastric lipases, some of which were crystallographically characterized. PMID- 1583688 TI - 1.7 A X-ray structure of the periplasmic ribose receptor from Escherichia coli. AB - The X-ray structure of the periplasmic ribose receptor (binding protein) of Escherichia coli (RBP) was solved at 3 A resolution by the method of multiple isomorphous replacement. Alternating cycles of refitting and refinement have resulted in a model structure with an R-factor of 18.7% for 27,526 reflections from 7.5 to 1.7 A resolution (96% of the data). The model contains 2228 non hydrogen atoms, including all 271 residues of the amino acid sequence, 220 solvent atoms and beta-D-ribose. The protein consists of two highly similar structural domains, each of which is composed of a core of parallel beta-sheet flanked on both sides by alpha-helices. The two domains are related to each other by an almost perfect 2-fold axis of rotation, with the C termini of the beta strands of each sheet pointing toward the center of the molecule. Three short stretches of amino acid chain (from symmetrically related portions of the protein) link these two domains, and presumably act as a hinge to allow relative movement of the domains in functionally important conformational changes. Two water molecules are also an intrinsic part of the hinge, allowing crucial flexibility in the structure. The ligand beta-D-ribose (in the pyranose form) is bound between the domains, held by interactions with side-chains of the interior loops. The binding site is precisely tailored, with a combination of hydrogen bonding, hydrophobic and steric effects giving rise to tight binding (0.1 microM for ribose) and high specificity. Four out of seven binding-site residues are charged (2 each of aspartate and arginine) and contribute two hydrogen bonds each. The remaining hydrogen bonds are contributed by asparagine and glutamine residues. Three phenylalanine residues supply the hydrophobic component, packing against both faces of the sugar molecule. The arrangement of these hydrogen bonding and hydrophobic residues results in an enclosed binding site with the exact shape of the allowed sugar molecules; in the process of binding, the ligand loses all of its surface-accessible area. The sites of two mutations that affect the rate of folding of the ribose receptor are shown to be located near small cavities in the wild-type protein. The cavities thus allow the incorporation of the larger residues in the mutant proteins. Since these alterations would seriously affect the ability of the protein to build the first portion of the hydrophobic core in the first domain, it is proposed that this process is the rate-limiting step in folding of the ribose receptor. PMID- 1583689 TI - Pre-nucleation crystallization studies on aminoacyl-tRNA synthetases by dynamic light-scattering. AB - Dynamic light-scattering (DLS) studies on solutions of proteins approaching their precipitation point were made with asparaginyl- (NRSEC), leucyl- (LRSEC) and valyl- (VRSEC) tRNA synthetases from Escherichia coli. The three aminoacyl-tRNA synthetases have not been crystallized previously. As a control system, we used E. coli polypeptide elongation factor Tu (EF-Tu). Apart from the different proteins used here, the methods we employed differed from previous studies in that (1) instead of making a series of measurements on individual samples at various concentrations, the protein solutions were titrated with the precipitants, and (2) the results of the light-scattering measurements were analysed by a new maximum entropy procedure that calculates a particle size distribution in a highly reproducible way. The particle size distributions of protein solutions titrated with precipitants showed two major peaks in most cases. For both peaks, relative areas and mean diffusion coefficients were determined. The diffusion constants were corrected for the viscosity of the solutions. From comparing the results on the proteins known to crystallize (EF Tu) with the amorphously precipitating systems (LRSEC, NRSEC) we find two necessary, but not sufficient, conditions for the formation of crystals: the diffusion coefficient of the monomer peak stays constant until very close to the precipitation point; the percentage of large aggregates stays small (less than 10% of the scattered light intensity) during the titration. For VRSEC, both ammonium sulphate and sodium citrate showed a low percentage of large aggregates and a constant diffusion coefficient of the main (protein monomer) peak below the precipitation point. This indicates that both would be possible precipitants for the crystallization of this enzyme. Crystallization trials using both these salts were carried out, and although no condition could as yet be found for obtaining crystals with ammonium sulphate solutions, crystals of the enzyme have been obtained with sodium citrate. PMID- 1583690 TI - Direct visualization of dynamics and co-operative conformational changes within RecA filaments that appear to be associated with the hydrolysis of adenosine 5'-O (3-thiotriphosphate). AB - Highly co-operative structural transitions and conformational changes can be directly observed in bundles of filaments formed by the RecA protein of Escherichia coli. These filaments have been formed with RecA protein, DNA and the ATP analog adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S). We show that while ATP-gamma-S has frequently been called non-hydrolyzable in the RecA literature, it is hydrolyzed by RecA with a kcat of about 0.01 to 0.005 min-1. This rate of ATP-gamma-S hydrolysis is significant to structural studies conducted on a time scale of hours. It has been shown that RecA subunits may be seen in different conformations within one particular form of RecA bundle. We now show that additional structural transitions take place within these bundles when they are allowed to incubate at 37 degrees C for several hours. This is the same time scale on which ATP-gamma-S is being hydrolyzed, and the suggestion that the observed structural transitions arise from the hydrolysis of ATP-gamma-S is supported by the fact that when the hydrolysis of ATP-gamma-S is inhibited (at 4 degrees C), the transitions are not observed. The transitions that occur are highly co-operative, with filaments as a whole changing their state over lengths of several thousand Angstroms. This shows that RecA filaments have an internal co operativity, and we suggest that this is important to their function in vivo. The motions of subunits that we visualize appear to be mainly rotational, and this can be used to infer information about the motions of RecA subunits associated with the RecA ATPase that occurs during the DNA strand exchange reaction. PMID- 1583691 TI - Crystallization of the exo(1,3)-beta-glucanase from Candida albicans. AB - An exoglucanase, with specificity for beta (1,3) linkages, from the cell wall of Candida albicans has been crystallized by the hanging drop method in the presence of polyethylene glycol 8000. The crystals, which diffract to better than 1.9 A resolution, belong to the orthorhombic space group P212121 with cell constants a = 60.2 A, b = 65.2 A, c = 96.5 A and with one molecule in the asymmetric unit. PMID- 1583692 TI - Site-specific recombinase, R, encoded by yeast plasmid pSR1. AB - The R gene product (R protein) of Zygosaccharomyces rouxii plasmid pSR1 catalyzes site-specific recombination within a 58 base-pair (bp) sequence present in the 959 bp inverted repeats of this plasmid. The R protein was produced in Escherichia coli and partially purified. The partially purified protein catalyzed site-specific recombination in vitro without the supply of an energy source. Recombination resulted in intramolecular inversion or deletion, depending on whether the orientations of the two recombination sites on the substrate plasmid were the same or opposite. Presumably, R protein is the only protein required for the recombination reaction. A circular DNA molecule appears to be a better substrate than a linear molecule in R-mediated in vitro intramolecular recombination. The R protein binds to a set of six 12 bp elements within the inverted repeats of pSR1. Two of these 12 bp elements are arranged in an inverted configuration with a 7 bp spacer in the 58 bp sequence. The R protein mediates strand cleavage in vitro at the junction between the 12 bp elements and the 7 bp spacer. The cleavage sites on the top and bottom strands are staggered and flanked by polypurine tracts that form part of the 12 bp elements. PMID- 1583693 TI - Common spatial arrangements of backbone fragments in homologous and non homologous proteins. AB - We have developed a new method of detecting common spatial arrangements of backbone fragments in proteins. This method allows corresponding fragments to occur in a different order in respective amino acid sequences. We applied this method to detect structural similarities between an acid protease, endothiapepsin, and all other proteins in the protein data bank. Significant similarities were found not only with other acid proteases but also with virus proteases and with proteins having different functions. The possible biological meaning of these similarities is discussed. PMID- 1583694 TI - Molecular analysis of Saccharomyces cerevisiae chromosome I. On the number of genes and the identification of essential genes using temperature-sensitive lethal mutations. AB - Previous analyses of Saccharomyces cerevisiae chromosome I have suggested that the majority (greater than 75%) of single-copy essential genes on this chromosome are difficult or impossible to identify using temperature-sensitive (Ts-) lethal mutations. To investigate whether this situation reflects intrinsic difficulties in generating temperature-sensitive proteins or constraints on mutagenesis in yeast, we subjected three cloned essential genes from chromosome I to mutagenesis in an Escherichia coli mutator strain and screened for Ts- lethal mutations in yeast using the "plasmid-shuffle" technique. We failed to obtain Ts- lethal mutations in two of the genes (FUN12 and FUN20), while the third gene yielded such mutations, but only at a low frequency. DNA sequence analysis of these mutant alleles and of the corresponding wild-type region revealed that each mutation was a single substitution not in the previously identified gene FUN19, but in the adjacent, newly identified essential gene FUN53. FUN19 itself proved to be non-essential. These results suggest that many essential proteins encoded by genes on chromosome I cannot be rendered thermolabile by single mutations. However, the results obtained with FUN53 suggest that there may also be significant constraints on mutagenesis in yeast. The 5046 base-pair interval sequenced contains the complete FUN19, FUN53 and FUN20 coding regions, as well as a portion of the adjacent non-essential FUN21 coding region. In all, 68 to 75% of this interval is open reading frame. None of the four predicted products shows significant homologies to known proteins in the available databases. PMID- 1583695 TI - Identification of a gene in Bacillus subtilis bacteriophage SPP1 determining the amount of packaged DNA. AB - The virulent Bacillus subtilis bacteriophage SPP1 encapsidates its DNA by a headful mechanism. Analyzing phage missense mutants, which package less DNA than SPP1 wild-type but show no other affected properties, we have identified a gene whose product is involved in the sizing of phage DNA during maturation. Characterization of this gene and its product provides an experimental access to the poorly understood mechanism of DNA sizing in packaging. The gene (gene 6 or siz) was cloned and sequenced. An open reading frame (ORF) coding for a 57.3 kDa polypeptide was identified. All the single nucleotide substitutions present in different siz mutants affect the net charge of that protein. The gene was further characterized by assignment of several nonsense mutations (sus) to the ORF. Phages carrying the latter type of mutations could be complemented in trans when gene 6 is provided by a plasmid. PMID- 1583696 TI - Evaluation of protein models by atomic solvation preference. AB - Important properties of globular proteins, such as the stability of the folded state, depend sensitively on interactions with solvent molecules. An excluded volume approximation to protein-solvent interaction, the solvent contact model, was used to derive atomic solvation preference parameters from a database of known protein structures. The ability of solvation preference to discriminate between correct and incorrect three-dimensional structures for a given sequence, or to identify the correct sequence placement in a given structure, was tested. Backbone co-ordinates were taken from experimentally known structures or hypothetical models and side-chain conformations (in rotamer space) were optimized by an efficient Monte Carlo algorithm using simulated annealing and simple potential functions. Discrimination by solvation preference was very clear between deliberately misfolded and correct globular models as well as between native-like and non-native-like topologies of combinatorially generated myoglobin models. Due to its statistical nature, the evaluation works best on entire protein models, while the identification of incorrect parts of models is more difficult. In one case locally incorrect chain tracing in a crystal structure was identified. The method is computationally fast compared to methods based on surface area calculations and is recommended for use as a diagnostic tool in model building based on sequence similarity, in folding simulations and in protein design. PMID- 1583697 TI - Stress proteins and myocardial protection. PMID- 1583698 TI - Flow cytometric analysis of isolated adult cardiomyocytes: vinculin and tubulin fluorescence during metabolic inhibition and ischemia. AB - Immunofluorescence and quantitative flow cytometry was used to determine if alterations in cytoskeletal proteins (vinculin and tubulin) occur during metabolic inhibition and ischemic incubation of isolated adult rat cardiomyocytes. Effects of cell shape changes on fluorescence, were controlled for by the contractile inhibitor, butanedione monoxime (BDM) and gated analysis. Flow cytometry differentiated rod- and round-shaped myocytes on the basis of forward and side scattering. Severe contracture of metabolically inhibited (iodoacetic acid and amytal) myocytes caused an artefactual increase in fluorescence intensity and a redistribution of tubulin into microblebs on the cell surface, which tended to mask specific losses of fluorescence. Fluorescence microscopy showed that round cells stained intensely for vinculin, but not for tubulin and that vinculin redistributed into coarse patches between 60 and 90 min, times which corresponded to small rebounds of fluorescence. With gated analysis, to exclude severely contracted round and squared cells, and with BDM inhibition of contracture, both metabolically inhibited and ischemic pelleted myocytes showed an early decrease in specific immunofluorescence staining for tubulin and vinculin, which preceded loss of cell viability, as determined by trypan blue staining. In both ischemic and metabolically inhibited cells, decreases of vinculin fluorescence preceded or coincided with increasing osmotic fragility. It is concluded that early cytoskeletal alterations of vinculin in ischemic and anoxic injury correlate with the development of osmotic fragility and irreversible myocyte injury. PMID- 1583699 TI - Platelet-activating factor (PAF) induces platelet/neutrophil co-operation during myocardial reperfusion. AB - The purpose of this study was to evaluate the role of platelet-activating factor (PAF) in cardiac dysfunctions occurring in ischemic isolated rabbit heart reperfused in the presence of polymorphonuclear neutrophils (PMN) and platelets (PLT). In a first set of experiments two different PAF-receptor antagonists were used to investigate the role of endogenous PAF released in the coronary vessels of post-ischemic heart. Mechanical and electrical dysfunctions occurring during reperfusion of ischemic heart were worsened in the presence of both PMN and PLT. Co-operation between PMN and PLT was suggested by the absence of effect when reperfusion was done with PMN alone, and by the significant enhancement of the effect of PLT after addition of PMN. The activation of PMN and PLT was mediated by PAF, since it was prevented by receptor antagonists SDZ 63-675 (3 x 10(-6)M) and WEB 2170 (3 x 10(-6)M). In a second set of experiments, the infusion of PAF in non-ischemic rabbit heart perfused with PMN and PLT was used to evaluate whether PAF can induce PMN-PLT interaction and reproduce the effects of ischemia. In this condition, the infusion of synthetic PAF (1 x 10(-7)M) induced mechanical and electrical dysfunctions similar to that occurring during reperfusion. The protective effect of both PAF receptor antagonists (SDZ 63-675 and WEB 2170) and of a leukotrienes receptor antagonist (FPL 55712, 1 x 10(-6)M) suggested that PAF is the mediator that triggers the co-operation between PMN and PLT, while leukotrienes produced by these cells are the final effector of cardiac dysfunction. In conclusion, these results suggested that PAF released during reperfusion of ischemic rabbit heart may amplify mechanical and electrical dysfunctions by triggering PMN-PLT co-operation. PMID- 1583700 TI - Metabolic effects of adenosine in the isolated perfused rat heart. AB - The effects of adenosine on myocardial substrate utilization were assessed in isolated Langendorff-perfused rat hearts. In unpaced hearts perfused at constant flow with insulin, adenosine inhibited oxidation of both glucose and palmitate with similar dose-dependency, without significant effects on effluent lactate+pyruvate. Significant effects of adenosine were observed at 0.1 microM adenosine. In a second series of paced hearts, perfusion pressure was kept constant during adenosine infusion by increasing the flow rate from 10 to 16.3 +/ 0.6 ml/min. Under these conditions, oxidation of both substrates was increased to a similar extent. Lactate+pyruvate output and total glycolytic flux were also increased. At zero or low insulin concentrations, the increases in substrate oxidation were similar to those seen at high insulin, but increases in lactate and pyruvate output and total glycolytic flux were abolished. It is concluded that adenosine does not preferentially increase glucose oxidation in this model. PMID- 1583701 TI - Metabolic fate of hypoxanthine and inosine in cultured cardiomyocytes. AB - The metabolic fate of labeled hypoxanthine and inosine, degradation products of adenine nucleotides, was studied in cultured beating cardiomyocytes, in order to assess the physiological significance of their contribution to salvage nucleotide synthesis in the heart. Inosine and hypoxanthine were found to be incorporated into nucleotides by a similar rate, but in the presence of 8-aminoguanosine, a potent inhibitor of purine nucleoside phosphorylase (EC 2.4.2.1), the rate of inosine incorporation into nucleotides was markedly reduced (by 75%), indicating that inosine incorporation to IMP (inosinic acid) occurs following its degradation to hypoxanthine. The proportion of hypoxanthine converted to IMP by hypoxanthine-guanine phosphoribosyltransferase (EC 2.4.2.8) is markedly greater than that degraded to xanthine and uric acid by xanthine oxidase (EC 1.3.2.3). However, close to 50% of the IMP formed was degraded to inosine by IMP 5' nucleotidase (EC 3.1.3.5). The results demonstrate the activity of the following futile cycle in the cardiomyocytes: hypoxanthine----IMP----inosine--- hypoxanthine. The rational for the activity of this energy consuming cycle is yet unclear. PMID- 1583702 TI - Chiari-I malformation associated with asymmetric sensorineural hearing loss. AB - Chiari-I malformation is a deformity of the structures of the posterior fossa in which there is inferior herniation of the cerebellar tonsils through the foramen magnum without significant caudal dislocation of the brainstem. Patients are usually asymptomatic until adulthood, when they commonly present with recurrent headaches, weakness, vertigo and/or imbalance, nystagmus and hearing loss. A review of 226 consecutive patients evaluated for asymmetric sensorineural hearing loss revealed 32 patients with retrocochlear pathology. Three of these patients were discovered to have a Chiari-I malformation by magnetic resonance imaging as their only pathology. We suggest a possible association between a Chiari-I malformation and isolated asymmetric sensorineural hearing loss secondary to long standing traction on the eighth cranial nerve. PMID- 1583703 TI - Extracranial carotid artery aneurysm in a child misdiagnosed as a parapharyngeal abscess: a case report. AB - An extracranial carotid artery aneurysm in a child misdiagnosed as a parapharyngeal abscess is presented. Diagnosis modalities of cervical masses and features of aneurysms are discussed. It is stressed that, regardless of age, in the presence of a pulsating and tender cervical or parapharyngeal mass, an aneurysm is probable. Prior to any intervention, at least non-invasive screening tests must be performed. Failure may lead to disastrous results. PMID- 1583704 TI - Metastatic spread of osteosarcoma to the temporal bone in a patient with Paget's disease: a case report. AB - Secondary tumors involving the temporal bone are comparatively rare. We report a case of secondary osteosarcoma presenting in the temporal bone which arose from a primary lesion in the tibia in a patient with Paget's disease. To our knowledge secondary osteosarcoma of the temporal bone has never previously been described. PMID- 1583705 TI - [Multivariate study of auditory perception using multi-electrode cochlear implants]. AB - The goal of this study was to determine the influence of auditory and cognitive factors in hearing or listening mechanisms with the Nucleus multielectrode cochlear implant. Accordingly, hearing sensitivity, psycho-acoustical masking functions and measures of temporal resolution were obtained from 14 adults with acquired deafness. In addition, six measures of open-set speech discrimination were introduced to represent a possible contribution of cognitive factors. Results indicated the contribution of both auditory and cognitive factors to speech understanding. Cognitive factors were most influential. Differences were also found in the relative importance of various cognitive factors, both before and after an intensive aural rehabilitation program. Initially, subjects relied more heavily on their ability to make efficient use of the linguistic redundancy of speech. At the end of the program, they paid more attention to speech acoustics, as a result of enhanced auditory spectral analysis and temporal resolution at about 2 kHz. PMID- 1583706 TI - Intranasal Xylocaine: a prognostic aid for pre-operative assessment of facial pain of nasal origin. AB - Many people with facial pain suggestive of sinus disease are ultimately proved, through extensive investigations, to have intranasal pathology without sinusitis. The middle turbinates in close proximity to other mucosal surfaces have been implicated as a possible cause of the rhinogenic pain. Surgical removal appears to provide relief in appropriately selected patient population. Pre-operative assessment to date has been mostly exclusional. Inference has been made to the efficacy of topical vasoconstrictive and combined vasoconstrictor-anesthetic agents as a diagnostic and prognostic aid for postoperative pain relief. Thirteen patients with middle turbinate hypertrophy, and symptoms suggestive of chronic rhinosinusitis were fully assessed clinically and radiographically. Significant sinus disease was ruled out. They were selected for middle turbinectomy with or without septoplasty. Topical Xylocaine was applied intranasally when patients were symptomatic. Postoperative follow-up suggests that the Xylocaine test may be a good prognostic aid for surgical outcome for craniofacial pain of apparent middle turbinate origin. PMID- 1583707 TI - Granular myringitis: a review. AB - Granular myringitis is the result of a localized chronic inflammation of the lateral surface of the tympanic membrane which is characterized by the development and persistence of granulation tissue over the involved area. The onset of the disease is insidious, and the symptoms, which are minor, are usually confined to chronic otorrhea and mild discomfort in the involved ear. Granular myringitis is a disease which is poorly understood and has received relatively little attention in the literature. The clinical features of this disease are outlined, the pathologic changes in the tympanic membrane illustrated, the literature reviewed and a strategy for treatment presented. PMID- 1583708 TI - An unusual complication of tracheoesophageal puncture for speech restoration. AB - Prosthetic voice rehabilitation post-laryngectomy is becoming more popular with otolaryngologists in Canada. However, as with any procedure, surgeons must be aware of potential complications. We present the first detailed report of a case in the creation of a dissecting false passage following tracheoesophageal puncture. PMID- 1583709 TI - A simple treatment for endochondral pseudocyst of the auricle. AB - Endochondral pseudocyst of the auricle is not an infrequent problem. It is not a serious condition, but annoying, and may lead to disfigurement of the auricle if left untreated. Most of the cases require surgical treatment. This article proposes a simple non-surgical treatment which includes needle aspiration followed by triamcinolone injection. Because of the satisfactory result, this procedure should be considered as a new choice of treatment for this condition. PMID- 1583710 TI - Use of free auricular composite graft in nasal alar/vestibular reconstruction. AB - Reconstruction of the nasal alar/vestibular complex following trauma or surgery presents a challenging problem. Options include bone, cartilage, and composite grafts as well as prosthetic materials. We present a case in which resection of an intranasal leiomyosarcoma, leaving a dome defect, was successfully reconstructed with an auricular composite graft. PMID- 1583711 TI - Bilateral carotid body tumors. PMID- 1583712 TI - Nasal lavage. PMID- 1583713 TI - Cherubism. AB - Cherubism is a rare inherited fibro-osseous disorder that affects the jaws, producing a characteristic facial appearance. Patients are normal at birth; however, by their second or third year of life they develop a fullness of the lower one half of their face and retraction of the lower eyelids that exposes a rim of sclera below the iris. The facial appearance is similar to a Renaissance cherub with its gaze toward heaven. A case of cherubism in a 19-year-old male, complicated by severe orbital compression resulting in diplopia, is presented. The patient was diagnosed at three years of age when he developed the characteristic cherub facies and severe dental anomalies that required surgical correction. At age 14, he underwent facial contouring surgery of his jaws. Orbital compression later developed due to lesions growing in the floor of his orbits. This was corrected by way of a subciliary approach to the orbit. The patient's facial appearance and visual function were markedly improved by the surgery. A review of the literature detailing this rare disease is discussed. PMID- 1583714 TI - The efficacy of nasal septal surgery. AB - Nasal septal deformity is a frequent clinical entity, and septoplasty comprises one of the most common procedures performed by otolaryngologists today. Its efficacy seems intuitive, however the literature reveals relatively few papers confirming its utility. In this study, all patients undergoing septal reconstruction (excluding septorhinoplasty) at three major teaching hospitals in Vancouver during the years 1988 to 1990 were reviewed retrospectively in a two pronged study. Information was collected concerning symptoms, physical findings and surgical technique. In the second phase, patients were contacted by telephone in a blinded fashion. Data was collected concerning patient satisfaction regarding various parameters including initial and ultimate symptom resolution, acceptance of nasal packing and postoperative complications. The following conclusions may be drawn: 1) Septoplasty was successful in relieving nasal obstruction in 70.5% of patients. 2) Turbinate surgery including outfracturing appears to significantly improve the outcome of surgery. 3) Rhinitis, including allergy, congestion, postnasal drip and rhinorrhea did not significantly affect success in relieving nasal obstruction. 4) Nasal packing did not significantly affect the outcome, but was the most frequently complained of aspect of the surgery. Therefore, we do not feel nasal packing is necessary. PMID- 1583715 TI - Fluconazole: a new option in the treatment of Candida mucositis and esophageal candidiasis. AB - Fluconazole is a new triazole antifungal agent with good activity against Candida and cryptococcal meningitis. It is well-tolerated and effective in immunosuppressed patients with oral-pharyngeal candidiasis. This review outlines the characteristics of fluconazole and discusses its role among the class of antifungal agents. PMID- 1583716 TI - Treatment of Meniere's disease with topical gentamicin: a preliminary report. AB - We evaluated the hypothesis that topical intratympanic gentamicin can relieve the vertigo of disabling Meniere's disease, reduce or ablate vestibular caloric excitability, and preserve hearing. Between July 1988 and June 1989, 33 patients were treated in the Dizziness Unit at the Sunnybrook Health Sciences Centre in a prospective controlled trial. This preliminary report presents the results of 29 patients with follow-up averaging 8.3 months and ranging from one to 18 months. All patients had either complete (86.2%) or substantial (13.8%) control of vertigo. Caloric excitability was ablated in 63% and reduced in 25.9% of subjects. Hearing was improved in 35.7%, unchanged in 39.3%, and worse in 25.0% of patients. In this preliminary review, the overall success rate for this treatment is 89.7% if control of vertigo and improvement in disability level are the criteria examined. PMID- 1583717 TI - Effects of deletions in the cytoplasmic domain on biological functions of human immunodeficiency virus type 1 envelope glycoproteins. AB - The role of the cytoplasmic domain of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins in virus replication was investigated. Deletion of residues 840 to 856 at the carboxyl terminus of gp41 reduced the efficiency of virus entry during an early step in the virus life cycle between CD4 binding and formation of the DNA provirus without affecting envelope glycoprotein synthesis, processing, or syncytium-forming ability. Deletion of residues amino terminal to residue 846 was associated with decreased stability of envelope glycoproteins made in COS-1 cells, but this phenotype was cell type dependent. The cytoplasmic domain of gp41 was not required for the incorporation of the HIV-1 envelope glycoproteins into virions. These results suggest that the carboxyl terminus of the gp41 cytoplasmic domain plays a role in HIV-1 entry other than receptor binding or membrane fusion. The cytoplasmic domain of gp41 also affects the stability of the envelope glycoprotein in some cell types. PMID- 1583718 TI - A structural polypeptide of the baculovirus Autographa californica nuclear polyhedrosis virus contains O-linked N-acetylglucosamine. AB - A structural glycopeptide, gp41, derived from the occluded virus of the baculovirus Autographa californica nuclear polyhedrosis virus was characterized. The peptide specifically bound wheat germ agglutinin but was not recognized by a panel of seven other lectins. Reactivity with wheat germ agglutinin was eliminated by treatment of gp41 with beta-N-acetylglucosaminidase, indicating that N-acetylglucosamine (GlcNAc) was present as terminal residues. gp41 was efficiently galactosylated by galactosyltransferase only in the presence of Nonidet P-40, suggesting that GlcNAc residues are not exposed on the surface of the virion. Metabolic labelling of gp41 with [3H]GlcNAc occurred in the presence of tunicamycin. The carbohydrate was released by alkaline borohydride treatment and comigrated with N-acetylglucosaminitol in descending paper chromatography. The data indicate that gp41 contains single residues of GlcNAc O glycosidically linked to the polypeptide chain. Evidence suggesting that gp41 is located in the region between the envelope membrane and the capsid (defined here as the tegument) of the occluded virus is also presented. PMID- 1583719 TI - Mechanism of coronavirus transcription: duration of primary transcription initiation activity and effects of subgenomic RNA transcription on RNA replication. AB - Previously, we established a system whereby an intergenic region from mouse hepatitis virus (MHV) inserted into an MHV defective interfering (DI) RNA led to transcription of a subgenomic DI RNA in helper virus-infected cells. By using this system, the duration of a primary transcription initiation activity which transcribes subgenomic-size RNAs from the genomic-size RNA template in MHV infected cells was examined. Efficient DI genomic and subgenomic RNA synthesis was observed when the DI RNA was transfected at 1, 3, 3.5, 5, and 6 h postinfection, indicating that all activities which are necessary for MHV RNA synthesis are present continuously during the first 6 h of infection. The effect of subgenomic DI RNA synthesis on DI genomic RNA replication was then examined. Replication efficiency of the DI genomic RNA which synthesized the subgenomic RNA was approximately 70% lower than that of DI genomic RNA which did not synthesize the subgenomic DI RNA in MHV-infected cells. Cotransfection of two different-size DI RNAs demonstrated that replication of the larger DI RNA was strongly inhibited by replication of the smaller genomic DI RNA. Cotransfection of two DI RNA species of the same length into MHV-infected cells demonstrated that reduced replication of the genomic DI RNA which synthesizes the subgenomic RNA did not affect the replication of cotransfected DI RNA, demonstrating that the reduction in DI genomic RNA replication works only in cis, not in trans. Therefore, the previously proposed hypothesis that coronavirus, subgenomic RNA synthesis may inhibit the replication of genomic RNA by competing for a limited amount of virus derived factors seems unlikely. Possible mechanisms of coronavirus transcription are discussed. PMID- 1583720 TI - Differential factor binding at the promoter of early baculovirus gene PE38 during viral infection: GATA motif is recognized by an insect protein. AB - Regulatory elements interacting with DNA-binding proteins have been investigated in the promoter sequence of the early PE38 gene in the Autographa californica nuclear polyhedrosis virus (AcNPV). A GATA motif located 50 nucleotides upstream of the PE38 transcriptional start site is recognized differentially in the course of infection. As demonstrated by footprint and gel mobility shift assays, the GATA sequences TTATCT are protected by nuclear extracts from uninfected Spodoptera frugiperda cells and from S. frugiperda cells early postinfection (p.i.) but not by S. frugiperda cell extracts isolated 40 h p.i. We have compared the binding capacity of the insect GATA-like protein with that of the vertebrate GATA-1 factor identified as erythroid-specific factor. Our results indicate that a factor present in mouse erythroleukemia cells, presumably GATA-1, can bind to the insect GATA motif and vice versa. Evidence from transient expression studies suggests that the mutated GATA sequences do not influence PE38 promoter activity in cell culture. PMID- 1583721 TI - Role of N-linked oligosaccharides in processing and intracellular transport of E2 glycoprotein of rubella virus. AB - The role of N-linked glycosylation in processing and intracellular transport of rubella virus glycoprotein E2 has been studied by expressing glycosylation mutants of E2 in COS cells. A panel of E2 glycosylation mutants were generated by oligonucleotide-directed mutagenesis. Each of the three potential N-linked glycosylation sites was eliminated separately as well as in combination with the other two sites. Expression of the E2 mutant proteins in COS cells indicated that in rubella virus M33 strain, all three sites are used for the addition of N linked oligosaccharides. Removal of any of the glycosylation sites resulted in slower glycan processing, lower stability, and aberrant disulfide bonding of the mutant proteins, with the severity of defect depending on the number of deleted carbohydrate sites. The mutant proteins were transported to the endoplasmic reticulum and Golgi complex but were not detected on the cell surface. However, the secretion of the anchor-free form of E2 into the medium was not completely blocked by the removal of any one of its glycosylation sites. This effect was dependent on the position of the deleted glycosylation site. PMID- 1583722 TI - Human immunodeficiency virus type 2 infection and fusion of CD4-negative human cell lines: induction and enhancement by soluble CD4. AB - We describe human immunodeficiency type 2 (HIV-2) strains which induce cell-to cell fusion and infect certain CD4- human cell lines. Soluble CD4 (sCD4) induces or enhances fusion by most HIV-2 strains tested. Soluble CD4-immunoglobulin G chimeras and conjugates of sCD4 and antibody to the third domain of CD4 block HIV 2 fusion of CD4- cells. We conclude that HIV-2 can enter CD4- cells via an alternative cell surface receptor to CD4. While some strains entered efficiently, others retained a dependency on an interaction with sCD4 to initiate changes in the virion envelope required for membrane fusion. PMID- 1583723 TI - Derivation of neurotropic simian immunodeficiency virus from exclusively lymphocytetropic parental virus: pathogenesis of infection in macaques. AB - Neurological disease resulting from lentivirus (including human immunodeficiency virus) infections is usually caused by a strain of virus that replicates productively in microglia in vivo and in macrophage cultures in vitro. We undertook this study using the model of simian immunodeficiency virus in macaques (SIVmac) to test the hypothesis that macrophage tropism is a prerequisite for neurotropism of the virus. Using molecularly cloned SIVmac239, a virus which is lymphocyte- but not macrophagetropic, we showed that this virus failed to infect brain after intracerebral (i.c.) inoculation into two macaques. Rather, these inoculations resulted in disseminated infection in lymphoid organs and the bone marrow. Two sequential passages of infected bone marrow cells inoculated i.c. into new macaques resulted in severe neurological disease and classical neuropathological lesions. Virus obtained from affected brain answered the hypothetical question: it was neurotropic and macrophagetropic. New findings in the study were that both lymphocyte- and macrophage-tropic viruses were present in the animals, but the viruses localized in different tissues: the lymphotropic virus in the spleen, lymph nodes, and plasma and the macrophagetropic virus in the brain and lungs. To determine whether the brain virus was preferentially neurotropic and whether it had neuroinvasive properties, infectious brain homogenate was inoculated into one animal i.c. and into two others peripherally. The i.c. inoculated animal developed fatal encephalitis 5 months later, and examination of tissues showed cell-free virus only in brain homogenates. Only microglia were infected despite persistent viremia and infection in bone marrow cells. The two macaques inoculated peripherally remained healthy and were euthanized at 6 months. Virus replication was detected only in the bone marrow cells and peripheral blood mononuclear cells. No infection in any macrophage population in visceral organs was detected, and the virus did not invade the brain. The strictly microglial specificity of this virus suggested that different macrophage populations in the body may select specific phenotypes of lentivirus from the quasispecies of virus in the bone marrow. This could provide the basis for specific disease affecting different organ systems. PMID- 1583724 TI - Mutations in the env gene of friend spleen focus-forming virus overcome Fv-2r mediated resistance to Friend virus-induced erythroleukemia. AB - Although Fv-2r homozygous mice are resistant to leukemias induced either by an erythropoietin-encoding virus or by wild-type Friend virus (FV) (M. E. Hoatlin, S. L. Kozak, F. Lilly, A. Chakraborti, C. A. Kozak, and D. Kabat, Proc. Natl. Acad. Sci. USA 87:9985-9989, 1990), they are susceptible to some variants of FV (R. A. Steeves, E. A. Mirand, A. Bulba, and P. J. Trudel, Int. J. Cancer 5:349 356, 1970; R. W. Geib, M. B. Seaward, M. L. Stevens, C.-L. Cho, and M. Majumdar, Virus Res. 14:161-174, 1989). To localize the virus gene involved in influencing the host range, we cloned and sequenced the env gene of the BB6 variant of FV (Steeves et al., Int. J. Cancer 5:349-356, 1970). In comparison with the wild type env gene, the BB6 variant contains a 159-bp deletion that eliminates the membrane-proximal portion of the extracellular domain and 58 point mutations resulting in 13 amino acid changes. Substitution of the variant env gene for the wild-type env gene resulted in a recombinant virus that produced a Friend virus like disease in Fv-2r homozygotes. Our results identify the spleen focus-forming virus env gene as the viral gene involved in this virus-host interaction. Additionally, they suggest that the product of the Fv-2r gene modifies the interaction between the spleen focus-forming virus envelope protein and the erythropoietin receptor. PMID- 1583725 TI - Suppression of virus-specific antibody production by CD8+ class I-restricted antiviral cytotoxic T cells in vivo. AB - The question of whether virus-induced immunosuppression includes the antibody response against the infecting virus itself was evaluated in a model situation. Transgenic mice expressing the T-cell receptor (TCR) specific for peptide 32-42 of lymphocytic choriomeningitis virus (LCMV) glycoprotein 1 presented by Db reacted with a strong transgenic cytotoxic T-lymphocyte (CTL) response starting on day 3 after infection with a high dose (10(6) PFU intravenously [i.v.]) of the WE strain of LCMV (LCMV-WE); LCMV-specific antibody production in the spleen was suppressed in these mice. Low-dose (10(2) PFU i.v.) infection resulted in an antiviral antibody response comparable to that of the transgene-negative littermates. The induction of suppression of LCMV-specific antibody responses was specifically mediated by CD8+ TCR transgenic CTLs, since the LCMV-8.7 variant virus (which is not recognized by transgenic TCR-expressing CTLs because of a point mutation) did not induce suppression. In addition, treatment with CD8 monoclonal antibody in vivo abrogated suppression. Once suppression had been established, it was found to be nonspecific. The abrogation of antibody responses depended on the relative kinetics of the antibody response involved and the kinetics of the anti-LCMV CTL response. Analysis of T- and B-cell subpopulations showed no significant changes, but immunohistochemical analysis of spleens revealed extensive destruction of follicular organization in lymphoid tissue by day 4 in transgenic mice infected with LCMV-WE but not in those infected with the CTL escape mutant LCMV-8.7. Impairment of antigen presentation rather than of T or B cells was also suggested by adoptive transfer experiments, showing that transferred infected macrophages may improve the anti-LCMV antibody response in LCMV-immunosuppressed transgenic recipients; also, T and B cells from suppressed transgenic mice did respond in irradiated and virus-infected nontransgenic mice with antibody formation to LCMV. Such virus-triggered, T-cell-mediated immunopathology causing the suppression of B cells and of protective antibody responses, including those against the infecting virus itself, may permit certain viruses to establish persistent infections. PMID- 1583726 TI - Ribosomal frameshifting efficiency and gag/gag-pol ratio are critical for yeast M1 double-stranded RNA virus propagation. AB - About 1.9% of ribosomes translating the gag open reading frame of the yeast L-A double-stranded RNA virus positive strand undergo a -1 frameshift and continue translating in the pol open reading frame to make a 170-kDa gag-pol fusion protein. The importance of frameshifting efficiency for viral propagation was tested in a system where the M1 (killer toxin-encoding) satellite RNA is supported by a full-length L-A cDNA clone. Either increasing or decreasing the frameshift efficiency more than twofold by alterations in the slippery site disrupted viral propagation. A threefold increase caused by a chromosomal mutation, hsh1 (high shifter), had the same effect. Substituting a +1 ribosomal frameshift site from Ty1 with the correct efficiency also allowed support of M1 propagation. The normal -1 frameshift efficiency is similar to the observed molar ratio in viral particles of the 170-kDa gag-pol protein to the 70-kDa gag gene product, the major coat protein. The results are interpreted in terms of a packaging model for L-A. PMID- 1583727 TI - A second envelope glycoprotein mediates neutralization of a pestivirus, hog cholera virus. AB - Several monoclonal antibodies (MAbs) raised against hog cholera virus (HCV) reacted with the HCV structural glycoprotein gp44/48 and neutralized the virus. The presence of HCV gp44/48 on the viral surface was directly demonstrated by immunogold electron microscopy. Eight anti-HCV gp44/48 MAbs were tested by immunoperoxidase assay against a panel of pestivirus strains. Each MAb showed a distinct pattern of reactivity with HCV strains. It is suggested that the MAbs are well suited for epidemiological investigations of HCV outbreaks. PMID- 1583728 TI - A specific sequence with a bulged guanosine residue(s) in a stem-bulge-stem structure of Rev-responsive element RNA is required for trans activation by human immunodeficiency virus type 1 Rev. AB - We demonstrate that both the in vitro RNA binding and in vivo trans activation functions of human immunodeficiency virus type 1 Rev regulatory protein Rev require the presence of a 9-nucleotide 5'-CACUAUGGG-3' RNA motif on its cognate target, the Rev-responsive element RNA. For optimal Rev recognition, this sequence must be presented as a stem-bulge-stem structure and must contain at least two G's, one of which must be unpaired, and include some or all of the CACUAU sequence upstream of the three G's. Distal mutations which result in the base pairing of the G's eliminate the Rev response. The first G is crucial, but changes at the other G's are tolerated if at least one G is unpaired. The secondary structure or the three-dimensional orientation of the B1 and B2 stem loops of the Rev-responsive element are not relevant as long as the 5'-CACUAUGGG 3' sequence is preserved, with at least one bulged G residue. PMID- 1583730 TI - The GC box and TATA transcription control elements in the P38 promoter of the minute virus of mice are necessary and sufficient for transactivation by the nonstructural protein NS1. AB - To further define the transcriptional regulation of the P38 promoter in the minute virus of mice (MVM) genome, we constructed a series of internal deletion and linker scanning mutations. The mutant P38 constructs were assayed for transcriptional activity in vitro by primer extension analysis with nuclear extracts from murine A92L fibroblasts. Mutations which disrupted the GC box and TATA box severely reduced transcription in vitro. DNase I footprinting analysis confirmed that the murine transcription factor Sp1 bound to the GC box; however, no factors were observed interacting with a putative transcriptional activation regulatory element, termed the TAR element. The linker scanning mutations were analyzed in vivo by using a chloramphenicol acetyltransferase expression assay system, in both the presence and absence of constructs expressing the viral nonstructural protein, NS1. The ability of NS1 to transactivate the P38 promoter (up to 1,000-fold) depended entirely on the presence of intact GC and TATA box sequences. Disruption of the TAR element by either linker insertion mutations or an internal deletion did not inhibit transactivation of the P38 promoter. These results suggest that NS1 transactivates the P38 promoter indirectly by interacting with one or more components of the P38 core-transcription complex. PMID- 1583729 TI - Regulation of delayed-early gene transcription by dual TATA boxes. AB - The 39K Autographa californica nuclear polyhedrosis virus (AcMNPV) gene is highly expressed throughout the virus life cycle and is controlled by tandem promoters that exhibit features of early and late baculovirus promoters. Late transcripts initiate at a conserved TAAG motif, while early transcripts are heterogeneous and initiate near a conserved CAGT motif. To define the nucleotide sequences that regulate early transcription of the 39K gene, a series of mutations was generated by substitution of 10-bp stretches in the 39K promoter with a BglII linker. The effects of these mutations on transcription from the early promoter were determined by transient expression and primer extension assays in the presence of the viral trans-activator IE1 gene. Mutations in the region from -15 to -44 revealed that early 39K transcription was controlled by dual TATA boxes. These TATA boxes are separated by 10 bp, which partially accounts for the heterogeneity in early 39K transcripts. Transcripts initiating at the CAGT motif (proximal transcripts) were abolished by deletion of the proximal TATA box located at -29 relative to CAGT. Proximal transcripts were not affected by alterations in the distal TATA motif located at -39 relative to the CAGT. Similarly, transcripts initiating upstream of CAGT (distal transcripts) were eliminated by mutations in the distal TATA but were unaffected by substitutions in the proximal TATA box. Proximal transcripts were not detected with a plasmid containing mutations in the CAGT motif, although the distal transcripts were unaffected by CAGT mutations. When the sequences surrounding the initiation site for the distal transcripts were altered, the start site was shifted one nucleotide, but transcription was not quantitatively affected. These results suggest that early 39K transcription is controlled by two distinct TATA elements, one that is dependent on an initiator and one in which the site of initiation is determined by the TATA element alone. Mutations in an upstream region from -45 to -68 relative to the CAGT motif had a quantitative effect but did not alter the heterogeneous pattern of early transcripts, suggesting these sequences function as an upstream regulatory region. Analysis of late transcription indicated that the TAAG element was essential, while transcription was unaffected by other mutations. PMID- 1583731 TI - Neutralization of influenza virus by low concentrations of hemagglutinin-specific polymeric immunoglobulin A inhibits viral fusion activity, but activation of the ribonucleoprotein is also inhibited. AB - High concentrations of hemagglutinin-specific neutralizing polymeric monoclonal immunoglobulin A (IgA) inhibit attachment of the majority of type A influenza virus virions to cell monolayers and tracheal epithelium (H. P. Taylor and N. J. Dimmock, J. Exp. Med. 161:198-209, 1985; M. C. Outlaw and N. J. Dimmock, J. Gen. Virol. 71:69-76, 1990). A minority of virions attaches but is not infectious. Here, we report that a different mechanism operates when influenza virus A/Puerto Rico/8/34 (H1N1) is neutralized by low concentrations of monoclonal polymeric IgA or when A/fowl plague virus/Rostock/34 (H7N1) is neutralized by low concentrations of polyclonal rat secretory IgA. Under these conditions, neutralized virus attaches to cells and is taken up by them. However, upon entering the cell, the nucleoprotein (NP) of neutralized virus is found in the perinuclear cytoplasm, whereas NP from nonneutralized virus is concentrated in the nucleus itself. Further data show that the low-pH-mediated cell fusion activity of virions is inhibited by IgA in proportion to loss of infectivity. The possibilities that neutralization by low amounts of polymeric IgA is caused by inhibition of the virion fusion activity and that the aberrant distribution of NP from neutralized virus results from its failure to escape from the endosomal system were investigated by using A/PR/8/34 and the fusogenic agent polyethylene glycol (PEG) at pH 5.4. A/PR/8/34 attached to cells at 4 degrees C, with minimal internalization of the virus; treatment with PEG at pH 5.4 and 4 degrees C for 1 min led to infectious fusion of nonneutralized virus with the plasma membrane and, under these conditions, was more efficient than PEG at pH 7 or medium at pH 5.4. Neutralized virus which was attached to cells and treated with acidified PEG appeared to undergo primary and secondary uncoating, with its NP protein becoming concentrated in the nucleus and M1 becoming concentrated in the perinuclear cytoplasm. Although the distribution of NP and M1 was indistinguishable from infectious virus, infectivity was not restored. Thus, even when IgA-induced inhibition of fusion is reversed, virus is still neutralized. We suggest that infectious influenza virus undergoes an activation stage which may be the relaxation of the ribonucleoprotein structure needed to permit transcription or may be the removal of M1 bound to the ribonucleoprotein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1583732 TI - Amino acid sequence and structural properties of protein p12, an African swine fever virus attachment protein. AB - The gene encoding the African swine fever virus protein p12, which is involved in virus attachment to the host cell, has been mapped and sequenced in the genome of the Vero-adapted virus strain BA71V. The determination of the N-terminal amino acid sequence and the hybridization of oligonucleotide probes derived from this sequence to cloned restriction fragments allowed the mapping of the gene in fragment EcoRI-O, located in the central region of the viral genome. The DNA sequence of an EcoRI-XbaI fragment showed an open reading frame which is predicted to encode a polypeptide of 61 amino acids. The expression of this open reading frame in rabbit reticulocyte lysates and in Escherichia coli gave rise to a 12-kDa polypeptide that was immunoprecipitated with a monoclonal antibody specific for protein p12. The hydrophilicity profile indicated the existence of a stretch of 22 hydrophobic residues in the central part that may anchor the protein in the virus envelope. Three forms of the protein with apparent molecular masses of 17, 12, and 10 kDa in sodium dodecyl sulfate-polyacrylamide gel electrophoresis have been observed, depending on the presence of 2 mercaptoethanol and alkylation with 4-vinylpyridine, indicating that disulfide bonds are responsible for the multimerization of the protein. This result was in agreement with the existence of a cysteine-rich domain in the C-terminal region of the predicted amino acid sequence. The protein was synthesized at late times of infection, and no posttranslational modifications such as glycosylation, phosphorylation, or fatty acid acylation were detected. PMID- 1583733 TI - Comparison of the sequence of the gene encoding African swine fever virus attachment protein p12 from field virus isolates and viruses passaged in tissue culture. AB - Comparison of the amino acid sequence of the African swine fever virus attachment protein p12 from different field virus isolates, deduced from the nucleotide sequence of the gene, revealed a high degree of conservation. No mutations were found after adaptation to Vero cells, and a polypeptide with similar characteristics was present in an IBRS2-adapted virus. The sequence of the 5' flanking region was conserved among the isolates, whereas sequences downstream of the gene were highly variable in length and contained direct repeats in tandem that may account for the deletions found in different isolates. Protein p12 was synthesized in swine macrophages infected with all of the viruses tested. PMID- 1583734 TI - Specific NF-kappa B subunits act in concert with Tat to stimulate human immunodeficiency virus type 1 transcription. AB - NF-kappa B is a protein complex which functions in concert with the tat-I gene product to stimulate human immunodeficiency virus (HIV) transcription. To determine whether specific members of the NF-kappa B family contribute to this effect, we have examined the abilities of different NF-kappa B subunits to act with Tat-I to stimulate transcription of HIV in Jurkat T-leukemia cells. We have found that the p49(100) DNA binding subunit, together with p65, can act in concert with Tat-I to stimulate the expression of HIV-CAT plasmid. Little effect was observed with 50-kDa forms of p105 NF-kappa B or rel, in combination with p65 or full-length c-rel, which do not stimulate the HIV enhancer in these cells. These findings suggest that the combination of p49(100) and p65 NF-kappa B can act in concert with the tat-I gene product to stimulate the synthesis of HIV RNA. PMID- 1583735 TI - A cDNA clone of tomato mosaic virus is infectious in plants. AB - A cDNA clone of tomato mosaic virus (ToMV) genomic RNA was fused to the cauliflower mosaic virus 35S RNA promoter and the nopaline synthase gene polyadenylation signal. The transcriptional initiation site of the 35S RNA promoter was altered by in vitro mutagenesis so that the resulting transcripts start at the first nucleotide of the ToMV sequence. In addition, 12 nucleotides were inserted in the 5' untranslated region of the ToMV genome. This plasmid, pSLN, was used to inoculate several host plants of ToMV. Among five plant species tested, only Chenopodium quinoa accumulated large amounts of viral particles. The infectivities and systemic movements of the resulting viruses were the same as those of virus preparations obtained from a ToMV infection of C. quinoa. Primer extension analyses revealed that the 5' end of the viral genomic RNA was identical to those of RNAs isolated from virus progeny of an infection with T7 transcripts analogous to pSLN. Moreover, the insertion in the 5' untranslated region of the viral genome was stably maintained through several systemic passages of the virus. Thus, inoculation of plants with a plasmid containing a cDNA clone of an RNA virus under the control of a eukaryotic promoter seems to be a convenient alternative to the generation of in vitro transcripts and should facilitate the analysis of viral mutants generated at the DNA level. PMID- 1583736 TI - Synergistic activation of the human immunodeficiency virus type 1 promoter by the viral Tat protein and cellular transcription factor Sp1. AB - We have previously shown that the human immunodeficiency virus type 1 (HIV-1) Tat protein can activate a synthetic promoter containing consensus-binding sites for the cellular transcription factor Sp1. In this report, we show that a GAL-Tat fusion protein targeted via GAL4 DNA-binding sites can also trans activate an HIV 1 LTR promoter independently of the trans-activation response region. To show that the trans activation of the promoter by Tat directly involves the Sp1 protein, we have targeted a GAL-Sp1 fusion protein to the long terminal repeat promoter via upstream GAL4-binding sites. In the presence of Tat and GAL-Sp1, the promoter is synergistically trans activated at the transcriptional level, indicating that Tat and Sp1 functionally interact to trans activate the HIV-1 promoter. The Sp1 synergism is relatively specific, since another chimeric transcriptional activator, GAL-VP16, does not appear to be significantly synergistic with Tat. PMID- 1583739 TI - OSHA bloodborne pathogens standard aims to limit occupational transmission. PMID- 1583737 TI - Tumor necrosis factor alpha negatively regulates hepatitis B virus gene expression in transgenic mice. AB - It is well known that several inflammatory cytokines can modulate hepatocellular gene expression in a complex physiological process known as the hepatic acute phase response. Since hepatitis B virus (HBV) characteristically induces a vigorous lymphomononuclear inflammatory response in the liver during acute and chronic hepatitis, it is possible that hepatocellular HBV gene expression may also be modulated by one or more of the cytokines produced by these cells. Using bacterial lipopolysaccharide (LPS) as a surrogate inducer of inflammatory cytokines in vivo, we have tested this hypothesis in a transgenic mouse model system. In experiments with two independent transgenic mouse lineages that express the HBV envelope region under the control of either HBV or cellular promoters, we observed a 50 to 80% reduction in the hepatic steady-state content of a 2.1-kb HBV mRNA following administration of a single intraperitoneal dose of LPS. The regulatory influence of several inflammatory cytokines known to be induced by LPS was also examined in this system. The negative regulatory effect of LPS was consistently reproduced by the administration of a single nontoxic dose of tumor necrosis factor alpha, and it was occasionally observed following the administration of high doses of alpha interferon and interleukin-6, while no effect was detectable in response to high-dose interleukin-1 alpha or to gamma interferon. These observations suggest that tumor necrosis factor alpha and perhaps other cytokines may activate a heretofore unsuspected intracellular pathway that negatively regulates HBV gene expression. The intracellular mechanism(s) responsible for this effect and its pathophysiologic relevance remain to be elucidated. PMID- 1583740 TI - As number of trials increases, gene therapy begins to look promising for medicine's future. PMID- 1583738 TI - Cytoplasmic domain truncation enhances fusion activity by the exterior glycoprotein complex of human immunodeficiency virus type 2 in selected cell types. AB - To investigate the glycoprotein determinants of viral cytopathology, we constructed chimeric env genes between a noncytopathic strain of human immunodeficiency virus type 2 (HIV-2), designated HIV-2/ST, and a highly fusogenic and cytopathic variant derived from this virus. Expression of the resulting chimeric glycoproteins indicated that efficient syncytium formation in the human T-cell line Sup T1 mapped to the C-terminal region of the transmembrane (TM) glycoprotein subunit. In this region, the wild-type and cytopathic ST glycoproteins differed by only four amino acids and by the presence of a premature termination codon in the cytopathic variant. Subsequent site-directed mutagenesis indicated that the cytoplasmic domain truncation was responsible for the enhanced fusion activity. This modification, however, increased the fusion activity of the glycoprotein only in Sup T1 cells (in which the ST variant arose) but not in Molt 4 clone 8 or peripheral blood mononuclear cells. These observations indicate that the length of the cytoplasmic domain of the HIV-2 glycoprotein modulates the fusion activity of the exterior glycoprotein complex in a cell-specific manner. Such adaptability appears to permit the emergence of fusogenic variants during HIV-2 passage in vitro and may also regulate viral growth or cytopathic effects in selected cell types during natural infection in vivo. PMID- 1583741 TI - Medicine seeks to prevent more 'lost generations' of low-income children with avoidable problems. PMID- 1583742 TI - From the Federation of State Medical Boards of the United States. PMID- 1583743 TI - From the National Institutes of Health. PMID- 1583744 TI - From the Centers for Disease Control. Investigations of patients who have been treated by HIV-infected health-care workers. PMID- 1583745 TI - From the Centers for Disease Control. Outbreak of pharyngoconjunctival fever at a summer camp--North Carolina, 1991. PMID- 1583746 TI - From the Centers for Disease Control. Suction-drain injury in a public wading pool--North Carolina, 1991. PMID- 1583747 TI - Publication bias and the editorial process. PMID- 1583748 TI - Publication bias and the editorial process. PMID- 1583749 TI - Health USA. PMID- 1583750 TI - A critical analysis of RBRVS. PMID- 1583751 TI - A critical analysis of RBRVS. PMID- 1583752 TI - A critical analysis of RBRVS. PMID- 1583753 TI - A critical analysis of RBRVS. PMID- 1583754 TI - A critical analysis of RBRVS. PMID- 1583755 TI - A critical analysis of RBRVS. PMID- 1583756 TI - A critical analysis of RBRVS. PMID- 1583757 TI - A critical analysis of RBRVS. PMID- 1583758 TI - Percutaneous injuries during surgical procedures. AB - OBJECTIVE: To study the numbers and circumstances of percutaneous injuries (eg, needle sticks, cuts) that occur during surgical procedures. Surgical personnel risk infection with blood-borne pathogens from percutaneous injuries; some injuries might also place patients at risk by exposing them to a health care worker's blood. DESIGN: Observers present at 1382 surgical procedures recorded information about the procedure, the personnel present, and percutaneous injuries that occurred. SETTING: Four US teaching hospitals during 1990. PARTICIPANTS: Operating room personnel in five surgical specialties. MAIN OUTCOME MEASURES: Numbers and circumstances of percutaneous injuries among surgical personnel and instances in which surgical instruments that had injured a worker recontacted the patient's surgical wound. RESULTS: Ninety-nine injuries occurred during 95 (6.9%) of the 1382 procedures. Seventy-six injuries (77%) were caused by suture needles and affected the nondominant hand (62 injuries [63%]), especially the distal forefinger. The risk of injury adjusted for confounding variables by logistic regression was higher during vaginal hysterectomy (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.6 to 7.5) and lower during certain orthopedic procedures (OR, 0.2; CI, 0.1 to 0.7) than during 11 other types of procedures (reference group; OR, 1.0). Use of fingers rather than an instrument to hold the tissue being sutured was associated with 35 injuries (35%). Eighty-eight injuries (89%) were sustained by resident or attending surgeons; in 28 (32%) of the 88 injuries in surgeons, the sharp object that caused the injury recontacted the patient. CONCLUSION: Percutaneous injuries occur regularly during surgery, placing surgical personnel and, to a lesser extent, patients at risk for infection with blood-borne pathogens. Many such injuries may be preventable with changes in devices, techniques, or protective equipment; all such measures require careful evaluation to determine their efficacy in reducing injury and their effect on patient care. PMID- 1583759 TI - Death in the city. An American childhood tragedy. AB - OBJECTIVE: To look at trends in mortality and homicide rates in a specific metropolitan area, comparing the urban and suburban mortality trends. DESIGN: Descriptive study of mortality rates. Linear regression determined whether changes in mortality rates over time represented significant trends. SETTING: Industrial metropolitan area in the United States, population, 2,337,891. PARTICIPANTS: Pediatric deaths (1 to 18 years of age) in a 9-year period. Population characteristics: 36% black, 64% white, 50% each urban and suburban. MAIN OUTCOME MEASURES: Pediatric mortality rates for 1980 through 1988, grouped by urban vs suburban, age, gender, and race. Rates calculated using national census figures and plotted over time. RESULTS: There was a 50% increase in all cause mortality in the urban pediatric population as compared with no change or a slight decline in the suburban and national populations. The increase was found in the black urban population. Homicide showed the largest increase (252%). Firearm-related homicides accounted for the majority of homicide deaths. CONCLUSIONS: (1) There were significant differences in mortality between the urban and suburban pediatric populations. (2) The increase in homicides, specifically firearm homicides, in the urban population accounted for the increase in overall mortality rates. (3) The increase in homicide rates was significant only for the 10- to 14-year-old males and the 15- to 18-year-old male and female portions of the black urban population. (4) Firearm homicides have become epidemic in the black urban population we studied. PMID- 1583760 TI - Comparison of warfarin and external pneumatic compression in prevention of venous thrombosis after total hip replacement. AB - OBJECTIVE: To compare the effectiveness and safety of warfarin and external pneumatic compression (EPC) in prevention of venous thrombosis after total hip replacement. DESIGN: Prospective, randomized trial in consecutive patients, with blinded assessment of the primary end point. SETTING: University medical center and large community hospital. PATIENTS: Patients over age 18 years scheduled for elective primary total hip replacement were eligible. Of 254 patients interviewed, 232 were randomized, 220 patients had surgery and received prophylaxis, and 201 had venography. INTERVENTIONS: Patients were randomly assigned to prophylaxis with a device providing bilateral sequential EPC to both the calf and thigh or to receive warfarin in a low-intensity regimen beginning 10 to 14 days preoperatively. Prophylaxis was continued until venography. MAIN OUTCOME MEASURES: Venous thrombosis was diagnosed by venography between postoperative days 6 and 8. Bleeding was assessed by surgical blood loss, transfusion requirements, changes in hematocrit, and clinically identified bleeding complications. RESULTS: The total incidence of venous thrombosis was virtually the same in the warfarin and EPC groups (31% vs 27%), but the distribution of thrombi was different. Proximal thrombosis occurred in 12% of patients in the EPC group compared with only 3% in the warfarin group (P = .012, 95% confidence interval for difference, 2% to 18%). In contrast, calf vein thrombosis was more frequent in the warfarin group (21%) than in the EPC group (12%) (P = .021, 95% confidence interval for difference, 0% to 18%). Most proximal thrombi in EPC-treated patients were located within 15 cm of the femoral head and were not continuous with thrombi in deep calf veins. The high incidence of proximal thrombosis in the EPC group resulted in termination of the study by the safety monitoring committee. Blood loss and bleeding complications were similar in the two groups. CONCLUSION: Warfarin therapy is significantly more effective than EPC in preventing serious proximal vein thrombosis after total hip replacement. The greater effectiveness of warfarin therapy in preventing proximal vein thrombi and of EPC in preventing thrombosis in the calf suggests that there are differences in the pathogenesis of thrombosis in these two locations. PMID- 1583761 TI - Active compression-decompression. A new method of cardiopulmonary resuscitation. Cardiopulmonary Resuscitation Working Group. AB - OBJECTIVE: To describe and compare with standard cardiopulmonary resuscitation (CPR) in humans a new form of CPR that involves both active compression and active decompression of the chest. DESIGN: Patients in cardiac arrest in whom standard advanced cardiac life support failed were randomized to receive 2 minutes of either standard or active compression-decompression (ACD) CPR using a custom, hand-held suction device, followed by 2 minutes of the alternate technique. The ACD device was applied midsternum and used to perform CPR according to the guidelines of the American Heart Association: 80 compressions per minute, compression depth of 3.8 to 5 cm, 50% duty cycle, and constant-volume ventilation. Mechanical Thumper CPR was also compared in five patients. End-tidal carbon dioxide (ETCO2) concentrations and hemodynamic variables were measured. Transesophageal Doppler echocardiography was used to assess contractility, the velocity time integral (an analogue of cardiac output), and diastolic myocardial filling times. RESULTS: Ten patients were enrolled. The mean +/- SD ETCO2 was 4.3 +/- 3.8 mm Hg with standard CPR and 9.0 +/- 3.9 mm Hg with ACD CPR (P less than .0001). Systolic arterial pressure with standard CPR was 52.5 +/- 14.0 mm Hg and with ACD CPR, 88.9 +/- 24.7 mm Hg (P less than .003). The velocity time integral increased from 7.3 +/- 2.6 cm with standard CPR to 17.5 +/- 5.6 cm with ACD CPR (P less than .0001), and diastolic filling times increased from 0.23 +/- .09 seconds with standard CPR to 0.37 +/- .12 seconds with ACD CPR (P less than .004). Mechanical Thumper CPR consistently underperformed both standard and ACD CPR. Minute ventilation obtained in four patients during ACD CPR without endotracheal ventilation was 6.6 +/- 0.9 L/min. After 1 hour of standard CPR failed, three of 10 patients randomized to ACD CPR rapidly converted to a hemodynamically stable rhythm following 2 minutes of ACD CPR. CONCLUSION: ACD CPR is a simple manual technique that improved cardiopulmonary circulation in 10 patients during cardiac arrest. Although ACD CPR may have produced a return of spontaneous circulation in three patients refractory to standard measures, its impact on survival when used early in cardiac arrest remains to be determined. PMID- 1583762 TI - 'Antineoplastons'. An unproved cancer therapy. PMID- 1583763 TI - 'Binge' drinkers at Massachusetts colleges. Prevalence, drinking style, time trends, and associated problems. AB - OBJECTIVE: To compare drinking patterns among college freshmen with those found among students at similar schools 12 years ago, and to describe in detail the differences between "binge" drinkers and "nonbinge" drinkers. DESIGN: Mailed survey. SETTING: Fourteen 4-year colleges in Massachusetts. PARTICIPANTS: A total of 1669 first-year college students. MAIN OUTCOME MEASURES: The survey instrument contains a variety of self-report measures of drinking behaviors, attitudes, and consequences. "Binge" drinking is defined as the consumption of five or more drinks on one or more occasions in the past 2 weeks. MAIN RESULTS: The proportion of "frequent-heavy" drinkers remained constant between the 1977 and 1989 surveys (30% vs 31% of men; 13% vs 14% of women), but today's students get intoxicated more often and are more motivated to drink to get drunk. The proportion of students who said "to get drunk" was a "somewhat" or "very important" reason for drinking was two to three times as high in 1989 as in 1977. Among students surveyed in 1989, binge drinkers drank greater quantities, with greater regularity, and experienced more intoxication and alcohol-associated problems than did nonbinge drinkers. Close to half of the binge drinkers (46.5% of men, 48.3% of women) were drunk twice or more in the past month, compared with 5% or fewer of the nonbinge drinkers. CONCLUSIONS: The stability over time of the prevalence of frequent heavy drinking among college students indicates an apparent failure of both social and institutional policies to alter this behavior. Binge drinkers in particular appear to be a population whose drinking patterns and attitudes place them and those around them at increased risk for adverse consequences. PMID- 1583764 TI - Repeated coronary artery spasm in a young woman with the eosinophilia-myalgia syndrome. AB - We report a case of repeated coronary artery spasm with myocardial injury in a 37 year-old woman with the eosinophilia-myalgia syndrome. This patient did not have a medical history of cardiac-related illness or risk factors for coronary artery disease. The presence of eosinophil granule major basic protein in otherwise normal-appearing myocardial tissue, along with normal plasma levels of tryptophan metabolites, suggests that the mechanism of vasospasm in this patient might involve toxic eosinophil proteins or focal myocardial lesions, but not the production of excess tryptophan metabolites. PMID- 1583765 TI - Prospective evidence of a circadian rhythm for out-of-hospital cardiac arrests. AB - OBJECTIVES: Published studies have indicated a circadian rhythm in the occurrence of sudden cardiac death. However, these studies have involved either retrospective analyses of death certificates or analyses of data collected during studies of pharmacologic agents in selected populations. PURPOSE: To determine whether a circadian pattern could be clearly demonstrated in a prospective study of out-of-hospital sudden cardiac death in a large, unselected population. DESIGN: All adult cases of sudden death of presumed primary cardiac cause from a large urban population were prospectively evaluated over a 12-month period. The incidence of sudden cardiac death was analyzed using harmonic regression of the data tabulated by hour of the day. RESULTS: During the year of study, 1019 consecutive primary cardiac arrests were analyzed. A significant circadian pattern was found (P less than .0001) with the frequency of cardiac arrests increasing dramatically from 6 AM until noon. CONCLUSIONS: This prospective study of out-of-hospital cardiac arrest confirms the existence of a circadian rhythm. These data have important implications for future investigations concerning the pathophysiology of sudden cardiac deaths. PMID- 1583766 TI - Percutaneous injuries during operation. Who is at risk for what? PMID- 1583767 TI - New approaches to CPR. Four hands, a plunger, or a vest. PMID- 1583768 TI - A piece of my mind. The great wait. PMID- 1583769 TI - [Construction of a retroviral vector expressing human factor IX]. PMID- 1583770 TI - [New thrombolytic agents]. PMID- 1583771 TI - Plasminogen activation system of the platelets. PMID- 1583772 TI - [Investigation on a role of the fibrinolytic system in the maintenance of pregnancy and rupture of fetal membranes]. PMID- 1583773 TI - [Intracellular pH and PGI2 generation of human vascular endothelial cells]. PMID- 1583774 TI - [Heparin cofactor II inhibits thrombin-stimulated prostacyclin production by cultured vascular smooth muscle cells]. PMID- 1583775 TI - [Exposure of platelet fibrinogen receptors by a monoclonal antibody to GP IIb IIIa complex]. PMID- 1583776 TI - [Structure and function of GP V]. PMID- 1583777 TI - [Functional domains of von Willebrand factor]. PMID- 1583778 TI - [Acquired von Willebrand factor abnormalities]. PMID- 1583779 TI - [Activation of factors IX and X by factor VIIa]. PMID- 1583780 TI - [Structure of Russell's viper venom X activating enzyme (RVVX)]. PMID- 1583781 TI - [Recombinant factor VIII concentrate]. PMID- 1583782 TI - [Periodical changes in diagnosis and treatment of ovarian tumors]. AB - Malignant ovarian tumors are one of the most rapidly changing gynecological malignancies concerning diagnosis and treatment during the last 20 years. Clinical cases of about 1,000 malignant ovarian tumors including borderline malignancies enlisted in the Tokai Ovarian Cancer Study Group were analyzed for periodical improvement. A comparison between the 460 cases treated in 1974-1979 and the 574 cases treated in 1980-1985, revealed a nearly 20% improvement in the 5-year survival rate. Also another comparison was made for ovarian carcinoma according to the clinical stage. Periodical improvement was shown in all clinical stages in almost the same amount, which was about 20% or more. The 5-year death rate was compared in accordance with age of patient and histological type of the tumor. Dominant progression was observed in younger generation under forty years of age, and in serous carcinoma and yolk sac tumor. However, no progression was observed for patients in their sixties and unclassified carcinoma. Periodical changes of findings in autopsy were compared between cases autopsied in 1968 and in 1988, according to the annual paper reported by Japan Pathological Society. Number of autopsied cases for malignant ovarian tumors were increased 3 times in 1988. In 1968, nearly 60% of the malignant ovarian tumors were treated by doctors in internal medicine, surgery and radiology etc., rather than gynecology, which was partly because the primary site of the cancer was unknown during the clinical course and partly because the gynecologist gave up treatment of patients in advanced cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583783 TI - [An analysis of oncogene activation in ovarian carcinoma]. AB - Evidence is increasing that oncogenes are involved in the development and/or progression of gynecological malignancies including ovarian carcinoma. While histopathologic examination remains an indispensable tool in the diagnosis and evaluation of patients with ovarian carcinoma, the advancement of technology and the development of new knowledge regarding neoplastic transformation are providing a basis for new opportunities to improve patients care. In this review, a variety of techniques to study the abnormalities of oncogenes, especially of c myc oncogenes in clinical specimens of human ovarian malignancies are reviewed. Emphasis in placed on whether the techniques are feasible in routine clinical laboratories and have potential values to the care of patients with ovarian carcinoma. At this juncture, an examination of c-myc oncogene abnormalities at the DNA level appears to have a greater potentials in the field described above than those at mRNA and protein levels. PMID- 1583784 TI - [Ovarian epithelial tumors of borderline malignancy]. AB - Ovarian tumor is known to show histological variation. Each tumor shows various clinical behavior. Ovarian epithelial tumors consist of several types of histological findings. Epithelial tumors can be classified into benign, borderline malignancy and malignant for their biological behavior. Recently the therapeutic effectiveness against ovarian cancer is increasing in order to establish the operation technique and development of chemotherapeutic method with cisplatin. Therefore it is important that borderline malignant tumors which are said to have a good prognosis be defined from obviously malignant tumors to evaluate accurately the effectiveness of the therapy against the ovarian cancer. On the other hand, borderline malignant tumors with characters of a malignant tumor, must be distinguished from benign adenoma because long-term follow up is required. However, it is difficult to make an exact histological diagnosis of benign adenoma, borderline malignancy and malignancy because the histological criteria of borderline malignancy is lacking in concreteness. The histological criteria should be defined more clearly and concretely. For example, mitotic counts per 10 HPF of borderline malignancy and DNA ploidy. Next, because of good prognosis, we need a quick therapeutic guide line for borderline malignancy, especially for stage I and young women. PMID- 1583785 TI - [Diagnosis of ovarian tumor by measuring tumor markers]. AB - Values of CA125, CA19-9, TPA, CA72-4, BFP and LDH in sera were detected in 148 malignant ovarian tumors, 41 borderline malignant ovarian tumors, 71 benign ovarian tumors and 64 benign uterine diseases. A new cut-off value was determined by ROC graph for distinguishing malignant and borderline ovarian tumors from benign ovarian tumors. CA125 (cut off: 30 U/ml) was a highly sensitive marker for malignant and borderline malignant ovarian tumors, the value being 88.1% (52/59) and 81.8% (9/11), respectively. On the other hand, in 37 benign ovarian tumors, the positive rate was 21.6% and in 21 benign uterine diseases it was 52.4%. CA19 9 (cut off: 150 U/ml) was inferior to CA125, but it was an effective marker for mucinous ovarian tumors. TPA (cut off: 40 U/ml) was also a sensitive (84.7%, 50/59) marker of malignant ovarian tumors. CA72-4 (cut off: 4 U/ml) was a highly specific (87.0%, 60/69) marker of malignant ovarian tumors. Combination assays of CA125/CA19-9, CA125/TPA and CA125/CA72-4 were not effective. Usefulness of BFP for early malignant ovarian tumors was suggested. Seven cases of dysgerminoma showed extremely elevated LDH levels (1,248 +/- 886 IU/1/37 degrees C). Malignancy and histological type of ovarian tumors could be decided by combination assay of these tumor markers, before surgical operation. PMID- 1583786 TI - [Diagnosis of ovarian tumors by transvaginal Doppler ultrasound with color flow imaging]. AB - Ovarian carcinoma is a silent disease with few symptoms. Early detection of ovarian cancer is difficult. Transvaginal Doppler ultrasound with color flow imaging is a new technique in the evaluation of gynecological diseases. This method was used in the diagnosis of ovarian tumors in 39 women who were treated in the Department of Obstetrics and Gynecology, Nagoya University Hospital. Wave forms of the parenchymal tumor arteries or tumor surface arteries were compared by according to the pulsatility index (PI). 1/PI was 0.69 +/- 0.04 in benign tumor and 2.33 +/- 1.36 in malignant tumors (p less than 0.01). When the cutoff value of 1/PI was set at 0.8 (cutoff value of PI: 1.25), the accuracy of diagnosis was 84.6% (33/39). The accuracy of ultrasonographic pattern classification and CA125 were 74.4% (29/39) and 53.8% (21/39), respectively. In 18 tumors with low CA125 (less than 35 U/ml), 5 of 7 malignant tumors (71.4%) had high 1/PI (greater than 0.8), and benign tumor, low 1/PI (less than 0.8) or non detectable wave forms. This procedure should prove to be useful in the diagnosis of ovarian cancer. PMID- 1583787 TI - [The diagnosis of computed tomography (CT) and magnetic resonance imaging (MRI) in evaluation of the extension of ovarian carcinoma]. AB - To evaluate the utility of Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) in the diagnosis of malignant ovarian tumors, preoperative CT of 23 patients and MRI of 10 patients with ovarian cancer were analyzed on the basis of their surgical findings. The stage suggested by CT and the stage revealed by surgery coincided in 16 cases (69.6%). The stage was underestimated by CT in 6 cases and overestimated in one case. The minimal size that could be detected by CT examination was 2 cm. The stage tended to be underestimated by CT. MRI examination with its unique soft tissue contrast in multiple planes is a detailed display of pelvic organs. However, the contrast of upper abdominal cavity was not so good, because of respiratory artifact. Sometimes there were false negative MRI in lymphatic metastasis. Therefore, MRI is more helpful in distinguishing local distension to pelvic organs than CT. PMID- 1583788 TI - [An application of cytology for ovarian tumors]. AB - Cytology for ovarian tumors is not popular among doctors; however, sometimes it is very useful. Peritoneal cytology is essential for identifying the stage of patients with ovarian cancer. I examined numerous cases of cytology for ovarian tumors at a small private obstetrical and gynecological hospital (Horio Anjo Hospital) and a large public hospital (Nagoya City University Hospital). In hospitals such as Horio Anjo Hospital where there is no pathologist, "cytology in operating room" is useful for understanding the type of tumor, and determining its stage immediately after operation. At Nagoya City University hospital there were 138 cases of cytology for ovarian tumors from Oct. 1969 to May 1991. 27 out of 28 cases of benign tumors were diagnosed as negative, 9 out of 17 tumors of borderline malignancy were diagnosed as suspicious, and 84 out of 93 malignant tumors were diagnosed as positive. There were 18 cases which did not coincide with the histological diagnosis. In 9 cases, false diagnoses were caused by inadequate specimens. In 4 cases, false diagnoses were caused because the cells didn't look malignant. In 5 cases, false diagnoses were caused by cytologist errors. Therefore, it is essential to have adequate cell specimens in order to effectively detect and diagnose cytological cases. PMID- 1583789 TI - [Clinical usefulness of measurement of creatine contents in human erythrocytes as an index of erythropoiesis]. AB - The apparent half-life of erythrocytes in human blood have usually been measured using 51Cr or 32P-labeled erythrocytes. However, these methods are not suitable for routine methods for the determination of the half-life of erythrocytes because of requirement for both patient admission and complicated procedure. In 1967 Griffiths and Fitzpatrick suggested that creatine level in human packed erythrocytes reflected the mean-age of erythrocyte population. Fehr and Knob reported that erythrocyte creatine levels correlated closely with half-life of erythrocytes by means of 51Cr in severe and milder hemolytic anemias. In order to verify the clinical usefulness of measurement of creatine contents in human erythrocytes as an index of erythropoiesis, the number of reticulocytes counted by an automated reticulocyte counter (R-3000, Toa medical instruments) and creatine contents in erythrocytes measured by high performance liquid chromatography were compared. To evaluate the erythropoietic dynamics, we tried to determine the frequency distribution for individual erythrocyte cell age using erythrocyte creatine. The effect of erythrocyte life-span on hemoglobin A1c(HbA1c) was also appraised in normal blood sugar subjects. A significant increase (p less than 0.005) of erythrocyte creatine was found both in inactive autoimmune hemolytic anemia (AIHA) and in active AIHA. In severe AIHA, the frequency distribution of erythrocyte creatine shifted to the area of high level erythrocyte creatine, and showed a broad-pattern form corresponding to erythropoiesis. Negative correlation (r = -0.707, p less than 0.005) was revealed between erythrocyte creatine and HbA1c in normal blood sugar subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583790 TI - [Influence of aging and circadian fluctuation of fibrinolytic factors to the responses of these factors during venous occlusion test in healthy subjects]. AB - This study was aimed to clarify the influence of aging and circadian fluctuation of fibrinolytic factors to changes of tissue plasminogen (t-PA) and its inhibitor (PAI-I) during venous occlusion test. Venous occlusion was achieved by application of a sphygmomanometer cuff to the upper arm of elderly healthy subjects (n = 12) and young healthy subjects (n = 12) at 10:00 am and 4:00 pm. Plasma concentration of t-PA, free PAI-1 and total PAI-1 were measured by ELISA. The activity of t-PA was measured by bioimmunoassay using monoclonal antibody for t-PA. Circadian variation was observed in the change of t-PA activity and total PAI-1. These were highly increased in the evening. However, this phenomenon was different between age groups and increase of t-PA activity occurred in elderly subjects, whereas PAI-1 was observed in young subjects. In conclusion, circadian variation and the influence of age should be considered to evaluate results of venous occlusion test. PMID- 1583791 TI - [Effect of coix seed on the changes in peripheral lymphocyte subsets]. AB - Coix seed has been used in patients with verruca vulgaris and verruca planae juveniles, which have been considered to be induced by viral infection. Moreover, coixenolide, component in the seeds of coix, was reported to show anti-tumor activity. Possibly coix seed may have some influence on the cytotoxic activity of peripheral lymphocytes but there has been no data on this. Then we investigated the changes in number of cytotoxic lymphoid cells in seven volunteers before, during (four weeks) and after taking six coix seed tablets. Lymphocyte subsets were analyzed with monoclonal antibodies using a flow cytometer. The level of CD3+CD56+ (MHC-non restricted cytotoxic T cells) markedly increased at four weeks (before 1.9 +/- 0.5% vs four weeks 4.2 +/- 0.7%, p less than 0.01). The level of CD16+CD57- (the mature, most active natural killer cells) increased at three weeks (before 4.5 +/- 0.8% vs three weeks 5.2 +/- 0.8%, p less than 0.05). The level of CD3-CD56+ (natural killer cells) and the level of CD16+CD57+ (the variable active natural killer cells) decreased at one week and returned to normal level thereafter (before 13.7 +/- 2.1% vs one week 11.2 +/- 1.5%, p less than 0.05; before 8.8 +/- 1.5% vs one week 6.9 +/- 1.3%, p less than 0.05, respectively). These results indicate that coix seed modulate the peripheral blood lymphocyte subsets and may be effective to virus disease through the enhancement of cytotoxic activity. PMID- 1583792 TI - [Elevation of serum fucosyltransferase activities in malignant diseases--a sensitive tumor marker?]. AB - Fucosyltransferase (FT) is considered to be one of the most important glycosyltransferases responsible for the synthesis of cancer-associated carbohydrate chains such as CA19-9 and SLX. To determine whether FT is a sensitive tumor marker, we measured the enzyme activity of FT in sera from 136 cancer patients, 14 patients with benign diseases and 59 healthy controls, by using PA (pyridylamino)-labeled type II biantennary oligosaccharide derived from human serotransferrin as an acceptor substrate. Serum FT activity was significantly elevated in patients with cancer compared to healthy controls. Analysis of the enzyme products using HPLC and various fucosidases with different specificity revealed that alpha 1----3 FT was responsible for most of the elevation of the enzyme activity in sera from cancer patients. It should be stressed that the alpha 1----3FT derived from cancer patients transferred fucose to terminal lactosamine residues of type II biantennary oligosaccharides already attached to sialic acid. This indicates that the substrate specificity is clearly different from that reported in normal sera and tissues. In addition to alpha 1-- -3FT, some glycosidases including fucosidase were also elevated in sera from cancer patients. PMID- 1583793 TI - [Effect of bilirubin on serum fructosamine value, and the elimination of bilirubin by bilirubin oxidase]. AB - Fructosamine is examined as the index of past mean blood glucose levels. However, the fructosamine value appears to be influenced by the bilirubin. Therefore, we examined patients with hyperbilirubinemia showing suspected and definite jaundice. Abnormal fructosamine values were noted in 9 out of the 50 cases (18%) with suspected jaundice and 40 out of the 55 cases (72.2%) with definite jaundice. An experiment in which bilirubin was removed by bilirubin oxidase revealed that fructosamine levels in hyperbilirubinemia correlated with the values of bilirubin and increased fructosamine values were expressed as the values of bilirubin x 6.5. These results demonstrate abnormal fructosamine values not only in jaundice patients but also in those with suspected jaundice. These cases must be taken in the examination of fructosamine in patients with hyperbilirubinemia. PMID- 1583794 TI - [Evaluation of cardiac functions in patients with progressive systemic sclerosis (PSS)]. AB - Cardiac functions in 20 female patients with PSS were measured by ultrasound cardiography and compared with those of 10 healthy age-matched controls. The following results were obtained: 1) The patients with PSS showed the increases in left ventricular mass (LVmass), interventricular septal thickness (IVS) and left ventricular posterior wall thickness (LVPW) more than those of controls. 2) Diastolic descent rate (DDR) of patients decreased significantly in comparison with the healthy controls. 3) Right ventricular dimension (RVD) of patients were demonstrated to dilate more than those of controls. Conclusively ultrasound cardiography (UCG) is an available method for detecting the cardiac lesion of PSS. Abnormal signs were recognized even though their clinical features were limited to the extremities. PMID- 1583795 TI - [Mean platelet volume in diabetics]. AB - Platelet size is a determinant of platelet function. As platelet size in diabetics has been reported to be larger than normals, we have measured mean platelet volume (MPV) in diabetics simultaneously with fasting plasma glucose, fructosamine, and hemoglobin A1. MPV was positively correlated with fasting plasma glucose and fructosamine. In a sequential observations for a few months of 22 patients, all of whom showed decreasing fasting plasma glucose, MPV decreased in 10 patients, however, increased in only 2 patients. These findings suggest that MPV would be affected with diabetic control. PMID- 1583796 TI - [Recent advances in metabolic bone diseases of the elderly--calcium requirement and bone metabolic marker]. PMID- 1583797 TI - [Analysis of circulatory responses to orthostatic stress in the elderly]. AB - An active orthostatic stress test was conducted on 32 elderly patients over 65 years (elderly group) and 17 normal adults, for a comparative evaluation of their blood pressure, heart rates, and plasma catecholamine responses. In addition, 8 patients in the elderly group underwent a study of orthostatic responses with or without sublingual administration of isosorbide dinitrate (ISDN). The results of the orthostatic responses were evaluated by Schellong's method. The elderly group produced a positive reaction in one (3.1%), and a weakly positive reaction in two (6.3%), while the remaining 29 (90.6%) and all of the normal adults showed negative responses. The systolic blood pressure pattern that developed in response to rising among the elderly group was significantly different (p less than 0.001) from that of the normal adult group, but the response pattern seen in the heart rates of the former approximated that of the latter. The plasma norepinephrine concentration 10 minutes after rising increased significantly (p less than 0.001) in both the elderly and normal adult groups. This increase amounted to 1.5-fold in the elderly group and 2-fold in normal subjects, with a less prominent increase shown by the elderly. The norepinephrine levels of the elderly group were significantly higher than those of the normal adults both before and 10 minutes after rising (p less than 0.001 and p less than 0.01, respectively). In the elderly, ISDN caused a significant drop in the systolic blood pressure immediately after rising and a significant increase in the heart rate. Sublingual ISDN administration resulted in a significant increase in the norepinephrine level (p less than 0.05) in association with rising. These findings indicated that the circulatory responses to orthostatic stimuli are inappropriate as clinical data among the elderly and the administration of ISDN exaggerates this shortcoming further. PMID- 1583798 TI - [Assessment of the rate of successful transcranial Doppler recording through the temporal windows in Japanese with special reference to aging and sex]. AB - Transcranial Doppler method (TCD), newly developed in 1982, is ultrasound technology that measures physiologic parameters of blood flow in the major intracranial arteries. A major limitation of TCD is that, in some individuals, satisfactory recording is not possible, especially through the temporal windows. The purpose of the present study is to assess the rate of successful recording in TCD through the temporal ultrasonic windows in Japanese with special reference to aging and sex. In 423 Japanese (244 males and 179 females) aged from 25 to 93 years, measurement of blood flow velocity in basal cerebral arteries was performed by transcranial Doppler velocimeter with a 2 MHz pulsed wave Doppler probe. The signal was successfully recorded in 299 of 423 Japanese (71%). In Japanese males, successful measurement was more frequent (206/244; 84%) than in Japanese females (93/179; 52%). The rate of successful recording was evaluated in every decade from the twenties to the eighties, and it was found to decrease significantly according to age (100%, 94%, 91%, 74%, 66%, 67%, and 46%, respectively). In females, it significantly decreased in those older than 50 years old (100%, 100%, 93%, 61%, 36% 43%, and 27%, respectively), but not in males (100%, 88%, 89%, 81%, 88%, 83%, and 69%, respectively). These findings suggest that this noninvasive method has clinical usefulness for evaluating intracranial circulation but has limitation for assessing the intracranial lesions of elderly Japanese women. PMID- 1583799 TI - [Clinical and CT-findings in hemiballismus]. AB - We studied the correlation between clinical and CT-findings in 33 cases with hemiballismus. Of these 33 cases, 4 cases were examined by the authors and 29 cases were obtained from the literature. Cerebrovascular disease was present in 27 cases and the localization of the lesion was examined with CT. Of these 10 cases had lesions in the subthalamus, while 17 cases had lesions outside the subthalamus. In 6 cases, the location of the lesion was not recognized on CT. In cases with lesions outside the subthalamus, 11 cases had lesions in the putamen, 10 cases had lesions in the caudate. Therefore the lesion were largely located in the striatum. Typical hemiballismus was seen in 16 cases. In this group, 6 cases had lesions in the subthalamus, 5 cases had lesions in the putamen, and 3 cases had lesions in the caudate. Hemiballismus accompanied by hemichorea was seen in 17 cases. In this group, while 9 cases had hemichorea with ballismus, and 5 out of 9 cases had lesions in the caudate, 4 cases had lesions in the putamen. Thus, all lesions were located in the striatum. Eight out of 17 cases had hemiballismus with chorea. In these 8 cases, 4 cases had lesions in the subthalamus, these were 2 cases in the putamen, and 2 cases had lesions in the caudate. When all cases were examined in terms of clinical manifestations, 10 cases were considered to have lesions in the caudate and 7 out of 10 cases involved chorea. Ten cases had lesions in the subthalamus, while 6 out of 10 cases showed typical hemiballismus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583800 TI - [A case of late-onset Pick's disease with polyuria]. AB - A 72-year-old male was admitted to our hospital with a 2-year history of polyuria, prosopagnosia and aphasia. He showed characteristic clinical features of Pick's disease such as stereotyped verbal output and behavior and personality changes. CT and MRI scans showed marked atrophy in the bilateral anterior temporal lobes mild atrophy of the bilateral frontal lobes. SPECT scans revealed perfusion abnormalities in corresponding areas. A 6-hour-water deprivation test resulted in decrease in the urine volume and in concentration of the urine, suggesting abnormality of his secondary drinking behavior. Polyposia resulting in polyuria as a clinical manifestation may be due to stereotypic behavior which is often seen in Pick's disease. PMID- 1583801 TI - [A case of hyperinsulinemia due to hypersecretion of incretin]. AB - A 65-year-old male presented with postprandial hypoglycemic episodes. He had normal glucose tolerance, but plasma glucose reached a hypoglycemic level of 31 mg/dl at 120 min during 75 g oral glucose tolerance test. He had markedly increased insulin response to oral glucose but not to intravenous glucose, intravenous arginine or intravenous glucagon. Hyperresponse of insulin after oral but not intravenous glucose suggested the possible involvement of insulinotropic hormonal factor in the gut (incretin) in hyperinsulinemia of this patient. Therefore we evaluated the secretory response of glucagon like peptide-1 (GLP-1), a most likely candidate for incretin, to oral and intravenous glucose administration. Plasma GLP-1 response to oral glucose was almost five times greater than that of normal subjects. On the other hand, there was no significant response in plasma GLP-1 after intravenous glucose. These results suggest that hypersecretion of GLP-1 may be responsible for the hyperinsulinemia after oral glucose in this patient. PMID- 1583803 TI - [Brief review of pneumonology in the elderly]. PMID- 1583802 TI - [Recent progress in the treatment of elderly patients with cardiovascular diseases]. PMID- 1583804 TI - [Phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating myocardial fatty acid metabolism]. AB - A phase 2 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I BMIPP), a myocardial imaging agent developed for evaluating myocardial fatty acid metabolism, was performed in 197 patients with various heart diseases. The myocardial distribution of 123I-BMIPP did not change from early to late images in 88% of 91 patients with ischemic heart disease (IHD), while washout and/or fill in were observed in 45% of 55 patients with hypertrophic cardiomyopathy (HCM). In comparison with 201Tl in 165 patients with various heart diseases, the decrease in uptake was more profound with BMIPP in 56% and with 201Tl in only 4%. 123I BMIPP showed more severely decreased uptake in 83% of the patients with subacute myocardial infarction (15 to 30 days after the onset) and in 73% of the patients with HCM. High-quality SPECT images were obtained with 123I-BMIPP in 93% of 194 patients analyzed. However, the image quality in cardiomyopathy was inferior to that in IHD. The optimal injection dose range and standard dose of 123I-BMIPP were considered to be 74-148 MBq and 111 MBq, respectively. These findings suggest that 123I-BMIPP myocardial imaging is safe and useful for evaluating myocardial fatty acid metabolism in various heart diseases. PMID- 1583805 TI - [The influence of findings of coronary artery on myocardial salvage in acute myocardial infarction]. AB - 201Tl stress myocardial scintigraphy was performed in convalescent patients with acute myocardial infarction, to evaluate the influence of stenosis and collateral circulation of coronary artery in acute phase, on myocardial salvage in chronic phase. In 14 cases of unsuccessful coronary revascularization (complete occlusion), a complete defect of thallium imaging in chronic phase was seen in only one case of four cases with good collateral circulation, while eight of 10 cases with poor collateral circulation. In 16 cases of poor collateral circulation, six cases showed a complete defect, although the target vessel had improved to less than 75% of stenosis. However, in cases of good collateral circulation, no case showed a complete defect when the target vessel had improved to less than 75% of stenosis. The myocardial salvage is quite possible (p less than 0.05), when the coronary angiography in acute phase showed the forward flow (99% or 90% of stenosis) before coronary revascularization and/or good collateral circulation (Rentrop 2 degrees or 3 degrees). PMID- 1583806 TI - [Noninvasive estimation of site of lesion of left anterior descending artery with stress 201Tl myocardial SPECT images]. AB - Noninvasive estimation of site of lesion of left anterior descending artery (LAD) is important because of high morbidity of LAD lesion. Utility of stress 201Tl myocardial SPECT images for predicting site of LAD lesion characteristics of ischemic region induced by LAD lesion in the basal coronal image were studied in 53 patients with localized significant LAD lesion. Right margin of ischemic region at basal plane of SPECT images was determined by circumferential maximum count profile analysis of stress 201Tl myocardial images. Right margin of ischemic region induced by the just proximal lesion was 21 +/- 11 degrees, that by proximal lesion was -6 +/- 10 degrees and that by mid portion was -36 +/- 17 degrees. Sensitivity of right margin of ischemic region 0 for just proximal lesion was 100% (20/20) and that of right margin of ischemic region 0 for mid portion lesion was 100% (18/18). These results showed the possibility of detecting site of LAD lesion by stress 201Tl myocardial SPECT images. PMID- 1583807 TI - [Diagnostic utility of myocardial imaging using 123I-labeled beta-methyl iodophenyl pentadecanoic acid in ischemic heart disease]. AB - We evaluated the myocardial metabolism in the acute and subacute phases of myocardial infarction or unstable angina using 123I-labeled beta-methyl iodophenyl pentadecanoic acid (BMIPP). We then compared those findings with (1) myocardial perfusion images obtained with 201TlCl and (2) the regional and global left ventricular function determined by left ventriculography. Thirty-one patients were examined, consisting of 16 with acute myocardial infarction (6.8 +/ 2.6 days after onset), 8 with subacute myocardial infarction (35 +/- 3.0 days after onset) and 7 with unstable angina. The BMIPP images showed a larger uptake defect than 201TlCl images in the patients in the acute or subacute phase of myocardial infarction. This finding was especially remarkable in the acute phase after successful coronary revascularization therapy. Moreover, in such cases, the myocardial BMIPP uptake improved to the same degree as 201TlCl one month later. The decrease in myocardial uptake of BMIPP agreed well with the decrease in regional wall motion in the acute and subacute phases of myocardial infarction. In contrast, the myocardial perfusion of 201TlCl did not always agree with the regional wall motion in stunned or hibernating myocardium, where BMIPP showed an uptake-defect in the acute phase but improved in the subacute phase. Thus, BMIPP is surmised to be able to depict fatty acid metabolism in in vivo myocardial imaging. PMID- 1583808 TI - [Usefulness of 201Tl myocardial scintigraphy after dipyridamole infusion in patients with atherosclerotic vascular disease]. AB - To determine the utility for detecting ischemic heart disease (IHD), Dipyridamole thallium myocardial images (DIP-Tl) have been performed in the 103 patients with atherosclerotic vascular disease who can't exercise fully. Of 103 patients, there were 36 patients with arteriosclerosis obliterans (ASO), 31 patients with aneurysm of the abdominal aorta (AAA), 24 patients with aneurysm of the thoracic aorta (TAA) and 12 patients with dissecting aortic aneurysm (DAA). Clinical evidence of IHD was found in 20 patients with ASO, 10 with AAA, 7 with TAA and 4 with DAA respectively. Positive evidence of DIP-Tl was identified in 66% of 41 patients who had clinical evidence of IHD, and particularly in the patients with AAA (80%) and ASO (65%). On the other hand, in the patients without clinical evidence of IHD, positive evidence of DIP-Tl was identified in 19% of 62 patients and particularly in the patients with AAA (39%). In all patients, the percentage of the positive DIP-Tl ratio was 38%. And, when the 38% patients of the positive DIP-Tl were added to the patients of the negative DIP-Tl who had clinical evidence of IHD, almost half patients (51%) were considered to be complicated with IHD. This study suggests that the atherosclerotic vascular disease is highly complicated with IHD and DIP-Tl is useful to detect IHD. PMID- 1583809 TI - [New quantification of regional cerebral blood flow measurements by 123I-IMP SPECT with the rotating gamma camera--theory and validation of the look-up table method]. AB - A new method of quantifying regional cerebral blood flow (rCBF) measurements by N isopropyl-p-[123I]iodoamphetamine (123I-IMP) SPECT with a rotating gamma camera was designed. By assuming the 2 compartment model of the kinetic for 123I-IMP, two parameters of rCBF and distribution volume (Vd) of 123I-IMP from brom brain tissue to blood were obtained by the look-up table method and were derived from two simultaneous equations of the early and delayed images. The rCBF values of 3 cases (two normal adults and one brain infarct patient) were calculated by this method and were compared with the values of positron emission tomography (PET) measured at the same time. The average rCBF values in gray and white matter by this method were 40 ml/100 g/min, 27 ml/100 g/min, respectively and correlated significantly to rCBF values by PET (r = 0.598 (p less than 0.001)). PMID- 1583810 TI - [Clinical study on renal uptake in 67Ga scintigram]. PMID- 1583811 TI - [The thirteenth report on survey of the adverse reaction to radiopharmaceuticals (the 16th survey in 1990). Subcommittee of Safety Issue for the Radiopharmaceuticals Medical and Pharmaceutical Committee Japan Radioisotope Association]. PMID- 1583812 TI - The formation of gallstones. AB - There are two types of gallstones; cholesterol and pigment or bilirubinate. Cholesterol stones are formed in the gallbladder as a consequence of altered hepatocellular and gallbladder function. Overproduction of cholesterol by the liver is the major metabolic precedent of cholesterol gallstones and this may occur because of obesity, drugs, or other factors. Gallbladder factors which promote stone formation include hypomotility and the secretion of nucleating factors such as mucus glycoprotein. It is possible that both of these two factors are mediated by an increase in the prostaglandin production by the gallbladder mucosa. Pigment stones are either brown or black. Brown stones are formed of calcium bilirubinate and are usually associated with biliary infection. They occur in both the gallbladder and the bile ducts. Black pigment stones are extremely hard bilirubin polymers and are found mainly in the gallbladder. Biliary sludge is a necessary precedent of gallstones. It comprises cholesterol monohydrate crystals, glycoproteins and granules of calcium bilirubinate. PMID- 1583813 TI - Specificity of antibodies to single-stranded (ss) DNA in SLE patients with anti phospholipid syndrome. AB - Although the concept of anti-phospholipid syndrome has been proposed in patients with SLE and other rheumatic diseases, the immunological mechanism is still controversial. Recently, the crossreactivity between anti-cardiolipin antibody and anti-ssDNA antibodies has been discussed in relation to this syndrome. In the present study, the specificity such as the avidity and the crossreactivity of anti-ssDNA antibodies was examined to find a clue to clarify the question why all of anti-cardiolipin antibody positive patients do not have any specific clinical features, thrombosis and spontaneous abortion. The avidity of IgG anti-ssDNA antibodies was examined by salt elution studies in solid phase ELISA. The avidity of anti-ssDNA antibodies tended to be lower in 10 patients with specific features than in other 10 patients without those features. The crossreactivity of affinity purified IgG anti-ssDNA antibodies was investigated by competitive ELISA. Purified anti-ssDNA antibodies from 4 patients without specific features were slightly inhibited by negatively charged phospholipids, cardiolipin and phosphatidylserine, whereas purified anti-ssDNA antibodies from 2 patients with specific features, who were considered to have anti-phospholipid syndrome, were little inhibited by these phospholipids. The above results suggest that the specificity of anti-ssDNA antibodies appears, at least partly, in different manners whether specific features are present or absent in anti-cardiolipin antibody positive patients. Moreover, anti-ssDNA antibodies and anti-phospholipid antibodies may form separate groups of antibodies in patients with anti phospholipid syndrome. PMID- 1583814 TI - Effects of inline filtration on delivery of gentamicin at various flow rates. AB - The effects of inline filtration on delivery of gentamicin (GM) in the pediatric field were studied. The filter sets (Pall 0.20 micron. JMS 0.20 micron, and IVEX 2.022 micron) were studied using a simulated system. 10 mg of GM was injected into the system containing 5% dextrose in water (flow rate: 50 ml/hr, 10 ml/hr and 2 ml/hr) with horizontal and vertical settings of the inline filters. In case of 50 ml/hr, delivery of GM of Pall showed nearly the same delivery pattern as compared with no filter setting. However, JMS and IVEX 2 showed little differences. In case of 10 ml/hr and 2 ml/hr those differences became more significant. Delivery of GM was influenced by the priming volume of the filters, increasingly so at slow flow rates. Filter settings also influenced the delivery of GM. Furthermore, with regards to the results of the Vitamin K2 delivery and the technetium radiotracer method, JMS and IVEX 2 filters were observed to have some stagnation of drugs in the filter. Not only priming volumes of the filters affect delivery of drugs, filter designs also have an influence. The use of the inline filters is important in the pediatric field, but their charactaristics for drug delivery pattern should be considered. PMID- 1583815 TI - The development of a self-efficacy scale for exercise behavior. AB - The purpose of the study was to develop a self-efficacy scale for exercise behavior. The draft items of self-efficacy scale were chosen from the previous studies, and were modified to reflect the socioeconomic differences in the target population. Ratings were made on a 3-point Likert-type scale. The self-efficacy scale was administered to 647 employees in a Japanese manufacturing company in 1990. They were also asked to identify their exercise behavior as one of exercising more than once a week, or not exercising. Two factors were extracted by principal component factor analysis with varimax rotation, and those two factors had eigenvalue of greater than 1.0. They were named "high priority" and "independent factor". Cronbach's alpha coefficients were 0.90 and 0.84 for high priority and independent factor, respectively. The test-retest correlations for the high priority and the independent factor were 0.83 and 0.74, respectively. Both factor scores and scale scores were significantly higher in employees who habitually exercised compared with those who did not exercise. A significantly higher percentage of employees with high self-efficacy scores exercised regularly than those with lower self-efficacy scores. This study provided evidence of reliability and validity of the newly developed self-efficacy scale for exercise behavior in Japan. PMID- 1583816 TI - Effect of chronic exposure to acrylonitrile on subjective symptoms. AB - A cross-sectional study was performed to clarify the relationship between exposure to acrylonitrile (AN) and its effect on subjective symptoms by using a modified Cornell Medical Index (CMI) health questionnaire. The 7 acrylic fiber manufacturing factories surveyed were classified into 3 groups, namely, group L with a mean environmental acrylonitrile concentration of 1.8 ppm, group M with 7.4 ppm, and group H with 14.1 ppm. The total number of workers engaged in acrylic fiber manufacturing processes (acrylonitrile workers) and reference workers analyzed were 504 and 249, respectively. These consisted of 92 acrylonitrile workers and 108 reference workers in group L, 304 and 102 respectively in group M, and 108 and 39 respectively in group H. The mean values for length of exposure to acrylonitrile were 5.6 years in group L, 7.0 years in group M, and 8.6 years in group H. Neurotic status as determined by Fukamachi's criteria and Cornell Medical Index profiles did not show any AN-related differences between AN workers and reference workers in any of the groups. The subjective symptoms with significantly high prevalences in AN workers were "headache", "tongue trouble", "choking lump in throat", "fatigability", "general malaise", "heavy arms", and "heavy sweating". Except for "choking lump in throat" there was no relationship between the prevalence of symptoms and the length or level of exposure to acrylonitrile. These results suggested that long-term exposure to acrylonitrile at levels up to 14.1 ppm did not induce neurotic effects in acrylonitrile workers, but might cause some reversible subjective symptoms. PMID- 1583817 TI - Amyotrophic lateral sclerosis and parkinsonism-dementia complex on Guam: immunohistochemical studies. AB - The incidence of amyotrophic lateral sclerosis (ALS) and Parkinsonism-dementia complex (PDC) among the Chamorros in Guam is remarkably high. The patients with ALS have clinical and pathological characteristics similar to those in other parts of the world. The PDC patients display parkinsonism and progressive dementia and show a characteristic neuronal loss in certain parts of the central nervous system such as the hippocampus and substantia nigra. The Guamanian patients with ALS and PDC commonly have widespread Alzheimer's neurofibrillary changes, but without the associated senile plaques. We have applied immunohistochemical procedures to examine the expression of marker substances in Guamanian ALS and PDC. The markers studied include tau protein, ubiquitin, beta proteins, synaptophysin, calcineurin, Met-enkephalin, substance P and tyrosine hydroxylase. The results were compared with the findings in patients with Alzheimer's disease, Parkinson's disease, sporadic ALS and familial ALS. PMID- 1583818 TI - [Unfavorable blood lipid indicators in obesity]. AB - There were evaluated total serum cholesterol, cholesterol HDL, cholesterol LDL and triglycerides in relation to relative body weight, calculated according to Broca-Broughs formula and changes in body weight during last 5 years in 306 males aged 40-59 from the housing estate "Czechow" in Lublin. Mean total cholesterol, cholesterol LDL and triglycerides concentration were higher and cholesterol HDL was lower in overweight males in comparison with normal weight subjects. Significantly higher mean triglycerides concentration was stated in becoming overweight as compared with stable weight males. PMID- 1583819 TI - [A method of averaged ECG signal does not identify patients with ventricular tachycardia in disorders of intraventricular conduction]. AB - Conduction defect are known to delay and fragment the ecg signal and may be expected to cause changes on the signal-averaged ecg that mimic ventricular late potentials. The aim of our study was to asses whether signal-averaged ECG (SAE) identify patients (pts) with sustained ventricular tachycardia (VT) after myocardial infarction (MI) who display right or left bundle branch block (RBBB or LBBB). We studied 23 pts with RBBB and 25 pts with LBBB. SEA was recorded with bidirectional filters at 25-250 HZ and 40-250 Hz using Simson method. The total filtered QRS duration (QRSd), root mean square voltage in the terminal 40ms of the QRS (RMS40) and low amplitude signal duration less than 40uV (LAS40)) were measured. Signal-averaged parameters with a filter at 25-250 Hz were: [table: see text] Signal-averaged parameters with a filter at 40-259 Hz were: [table: see text] In conclusion SAE parameters do not allow separation of pts with sustained VT from pts with RBBB or LBBB after MI. These data indicate that conduction defects have effects on signal-averaged ecg parameters and may result in masking of ventricular late potentials. PMID- 1583820 TI - [Arrhythmogenic right-ventricular dysplasia--a case report]. AB - A case of arrhythmogenic right ventricular dysplasia (ARVD) in a 28 year old man is reported. Diagnosis was based on ECG, echocardiographic and scintigraphic findings. Echocardiography and scintigraphy revealed an enlarged right ventricle and normal left ventricle. The abnormalities specific for ARVD were free wall motion abnormalities, particularly akinetic areas and microaneurysms . Ventricular tachycardia and premature ventricular contractions of left bundle branch block (LBBB) pattern were recorded. A titer against mycoplasma and concentrations of immunoglobulins were normal. Anti-++ smooth muscle antibodies were detected. The patient was treated with amiodarone . There were no clinical, echocardiographic and ECG features of ARVD in the patient's brother. PMID- 1583821 TI - [Diagnosis of congenital anomaly of the inferior vena cava simulating aortic dissecting aneurysm by the method of transesophageal echo- cardiography]. AB - A case of 59 year old woman with acute myocardial infarction is presented in whom chest X-ray film revealed double outlined aortic arch suggestive of dissection. Transesophageal echocardiography (TEE) disclosed presence of two vascular canals in the place of thoracic aorta. Atypical dissection of thoracic aorta or a vascular anomaly were suspected because the image of dissection of intima was not characteristic and no connection between the two canals was found. Computed tomography ruled out presence of aortic aneurysm but the image of inferior vena cava was difficult for interpretation. Final diagnosis of congenital anomaly of inferior vena cava, originating from two iliac veins, passing along left side of the spine and emptying to the right atrium at the level of aortic arch, was established by means of cavography. Familiarity with TEE image of this vascular anomaly may allow avoidance of diagnostic error in cases suspected of aortic dissection. PMID- 1583822 TI - [Should hypotensive treatment be continued for the rest of the patient's life?]. PMID- 1583823 TI - [The minimum one should know about diseases of the veins]. PMID- 1583824 TI - [Thrombolytic therapy of myocardial infarction. Prognostic value of early reduction of elevation of ST segment]. AB - In-hospital mortality, infarction mass (estimated enzymatically) and electrocardiographic indexes (total ST-segments elevation, number of leads with R wave presence and total R-waves amplitude) were assessed in 532 patients with acute myocardial infarction, randomized to two treatment groups: 272 treated with streptokinase (SK) and 260 with heparin (H). Echocardiographic contractility indexes (contractility disturbances area index, contractility disturbances index, left ventricle diastolic diameter) and heart volume estimated from X-ray film were also assessed. There were no significant differences in mortality and infarction area between the two groups. In 175 patients total ST-segments elevation was reduced by at least 50%, in the rest 340 patients this reduction was less significant. In the group with early elevated ST-segment reduction there were less in-hospital deaths (p less than 0.01), smaller infarction mass (p less than 0.0001) and significantly less disturbed electrocardiographic contractility indexes. Results suggest that simple electrocardiographic index, namely reduction of ST-segment elevation by 50% after 2 hours of treatment may be a useful prognostic tool, independent on treatment options, as far as in-hospital mortality, necrosis mass and left ventricle contractility disturbances are concerned. PMID- 1583825 TI - [Arrhythmia. Its management at the leading British center]. PMID- 1583826 TI - [Lipoproteins and their metabolism]. PMID- 1583827 TI - [Disorders of glucose metabolism and hypertension--common etio-pathogenetic factors?]. PMID- 1583828 TI - [Use of cardiopulmonary bypass decreases leukocyte count and activation of the complement system]. AB - Platelet damage, complement activation and neutropenia during extracorporeal circulation are the result of blood contact with artificial surfaces, mainly in the oxygenator. To evaluate the biocompatibility of the ++auto-oxygenation technique of cardiopulmonary bypass (CPB) 2 techniques of extracorporeal circulation were compared in 40 patients undergoing elective coronary bypass surgery. Patients were studied in 2 groups, 20 patients in each: I (++auto oxygenation --patients lungs used in CPB) and II (conventional technique of CPB with bubble oxygenator). Several blood samples were taken before, during and after perfusion to estimate pulmonary leukocytes sequestration in all patients and additionally complement C3a and C5a anaphylatoxins + were measured (radioimmunoassays) in 6 patients of each group. During cardiopulmonary bypass the decline in leukocyte number was observed in both groups, but leukocyte count was higher in group I then II, due to the transpulmonary leukocyte sequestration which was higher in group II. The difference between leukocytes count in group II was 1.46 +/- 0.5 x 10(3)/mm3 vs only 0.34 +/- 0.2 x 10(3)/mm3 in group I, p less than 0.001. In postoperative period an increase in circulating white blood cells was observed in both groups when compared to pre-bypass time, but the difference between groups was non significant. The level of C3a increased in group I from 244 +/- 46 ng/ml to 418 +/- 34 ng/ml, in group II from 268 +/- 46 ng/ml to 521 +/ 65 ng/ml, p less than 0.001, but in group I the levels were significantly lower, p less than 0.001. The current study confirms that cardiopulmonary bypass results in significant leukocyte and complement activation and supports the theoreticaly better biocompatibility of CPB with lung over oxygenator. PMID- 1583829 TI - [Early and late ventricular fibrillation in myocardial infarction. Prognostic value of clinical and echocardiographic indicators]. AB - Our studies were aimed at evaluating the prognostic value of certain clinical and echocardiographic parameters as well as cardiac arrhythmias in patients with acute myocardial infarction complicated by ventricular fibrillation. The studies comprised 66 patients with previous ventricular fibrillation selected out of 637 patients undergoing treatment after recent myocardial infarction at the Clinic of Cardiology, Institute of Cardiology, Medical Academy, Poznan. The group included 51 males and 15 females aged 30-83, mean age 68. Anterior and/or lateral infarction were diagnosed in 44 patients (67%) whereas inferior and/or posterior infarction in 22 patients (33%). Fifty-eight patients (88%) had transmural infarction. The 2D and M-mode echocardiographic examinations and 24-hour Holter monitoring were performed in all patients. The group of patients resuscitated successfully was compared to the group of deceased patients. The observation period ranged from 1 to 7 years, mean 4 years. The analysis indicated that high mortality of patients with late ventricular fibrillation results from an extensive myocardial infarction and severe ventricular contractility disorders. In patients with late ventricular fibrillation, the main prognostic factor proves to be congestive heart failure and intraventricular conduction disorders with the fascicular and/or bundle-branch block types. PMID- 1583830 TI - [Diagnostic value of planar perfusion scintigraphy of the heart using Technetium Tc 99m with methoxy-isobutylisonitrile (MIBI)]. AB - 99mTc-MIBI (2 methoxy -isobutylisonitrile) belongs to the new generation of radiopharmaceuticals used for studies of myocardial perfusion. Particularly convenient characteristics of the compound prompted numerous studies of its usefulness for scintigraphic diagnostics of coronary artery disease and myocardial heart infarct (detection, localization, size). In the present paper the diagnostic utility of planar heart scintigraphy with 99mTc MIBI is assessed, the compound had been prepared in the Department of Nuclear Medicine, Medical University of Lodz. The scope of the study included detection of stress induced ischaemia and of permanent perfusion defects, treated as post infarct scars in myocardium. The study was made on 109 patients (78 males, 31 females; age 32-68 years). The first group comprised 56 patients with suspected or diagnosed coronary artery disease, however, without history of previous heart infarct. Results of stress and rest scintigraphy were juxtaposed with those of coronarography, which served as a reference method. In 25 patients the latter revealed critical (greater than 70%) stricture of 1 or 2 coronary arteries. In 31 patients of this group the vessels were either of normal appearance or only marginally stricture. Sensitivity, specificity and accuracy of the scintigraphy in diagnosis of ischaemia due to critical narrowing of coronary arteries amounted to 80, 84 and 82 per cent, respectively. Localisation of perfusion defects was adequate in 20 out of 31 vessels (64 per cent). The second group of patients included 53 individuals with previous heart infarct (25 and 11 had a transmural and nontransmural infarct of the anterior wall, respectively; in 12 and 5 a transmural and nontransmural infarct of the inferior wall was diagnosed, accordingly).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583831 TI - [Does the sinoatrial node conduction time depend on heart rate?]. AB - The informations about the dependence of sinoatrial conduction time (SACT) on heart rate (HR) are unequivocal. The aim of the study was to establish if such a dependence really exists. The study group comprised 24 patients (9 women and 15 men) aged 42-71 years, mean 55.8. All the patients presented atrial premature contractions of various etiology. No agents affecting heart electrophysiology were administered until the study was completed. In every patient SACT was estimated by means of the Strauss formula from the 24-hr ecg and from transoesophageal single impulse stimulation. SACT obtained from 24-hr ecg was 156.2 +/- 33.1 ms; whereas the one respectively, calculated from the transoesophageal stimulation was 119.0 +/- 21.0 ms. Despite a significant difference between the results (p less than 0.001), the SACT values obtained with both methods correlated well with each other (r = 0.712; p less than 0.01). The dependence of SACT on basic heart cycle length was observed in 9 pts during 24-h ecg (37.5%). Among these pts SACT was shortened with higher and lengthened with lower HR. In the remaining 15 pts this dependence didn't occur, neither it occurred in any patients examined with the single impulse stimulation. The results suggest that the dependence of SACT on HR is not a constant phenomenon and that it occurs only in a part of the examined population. PMID- 1583832 TI - [Effect of anti-arrhythmia drugs on the heart conduction system]. PMID- 1583833 TI - [Anti-arrhythmia treatment (clinical problems, classification of anti-arrhythmia drugs and personal experience]. PMID- 1583834 TI - [Patients with late-life vision damage in occupational rehabilitation. Preliminary ophthalmologic treatment, concomitant manifestations and an illustration provided by the growing number of patients with juvenile diabetes]. AB - The rehabilitation centre in Veitshochheim (near Wurzburg) offers different kinds of training programs for the adult visually handicapped. This is usually preceded by a long time of unemployment. Diabetes mellitus was the third most common disease at the centre and 25% of the patients with diabetes mellitus were already legally blind. In a retrospective study we looked at the medical and ophthalmological treatment and the education the 76 patients with diabetes mellitus had received before coming to the rehabilitation center. All charts from February, 87, to September, 90, were included in the study. According to the classification of visual acuities by the WHO we formed four groups (less than or equal to 1/50; 1/35-0.1; 0.125-0.3; greater than 0.3) and compared them with each other. In the groups with the lowest visual acuity the medical management of the diabetes mellitus had been much poorer than in the better groups. Related to the bad visual acuity was the higher incidence of proliferative diabetic retinopathy and the significantly lower percentage of panretinal lasercoagulations. 47% of the patients with diabetes mellitus had been trained in jobs that would not have been recommended to a potential visually disabled by an ophthalmologist or the office for labour exchange. Only in 10% of the cases could a job be maintained by the help of technical devices (including low vision aids). To ensure best medical treatment and counselling concerning the choice of an appropriate job a close team work between practising ophthalmologist, general practitioner, and the office for labour exchange is needed. Thereby the cost and psychological impact of a retraining program could hopefully be lowered. PMID- 1583835 TI - [Significance of the peripheral visual field for diagnosis of glaucoma]. AB - Investigated was the significance of semiquantitative tests of the peripheral visual field in glaucoma. For that purpose 793 visual fields of 793 glaucoma patients or glaucoma suspects and 338 visual fields of 338 normal controls (normal central 26 degrees--area) were analysed. Perimetry was performed with an Octopus 201 with the help of program G1, which tests 14 peripheral test locations. In the majority of the 455 glaucoma patients (pathological findings in the central visual field) the periphery was also disturbed. Much to our surprise however, the 338 glaucoma suspects (having normal central visual fields) showed the same frequency of peripheral visual field disturbance as the normals. This holds true for the total peripheral visual field, as well as for the individual test locations. Therefore it makes sense to limit perimetry in glaucoma patients to the central area, provided that the central area is quantitatively measured with an adequate testgrid. PMID- 1583836 TI - [Oculopression tonometry after argon laser trabeculoplasty]. AB - A group of 26 patients (14 female and 12 male ranging in age from 49 to 84 years) who had primary open angle glaucoma underwent argon laser trabeculoplasty in one eye each. Shortly before the laser treatment, and one and twelve (7-14) weeks after the treatment suction cup oculopression tonometry was performed with an increase of intraocular pressure according to 1.8 x actual intraocular pressure. A therapeutically significant decrease of intraocular pressure was observed already one week thereafter, but findings become more significant after a longer follow up. The decrease of intraocular pressure and results of oculopression tonometry indicate that the measured resistance to aqueous outflow decreased significantly after argon laser trabeculotomy. PMID- 1583837 TI - [Effect of argon laser trabeculoplasty on unrestricted outflow of aqueous humor in eyes with simple glaucoma]. AB - In this prospective study we used the oculopressions-tonometry (OPT) for determination of the aqueous humor outflow facility (C). 53 phacic eyes with glaucoma simplex were examined pre- and postoperatively. One hour after operation C decreased from 0.15 to 0.14. In correlation to this fact the IOD increased. After 7 days C was higher already than preoperatively, 30 days and 6 months after operation C showed normal values. After 6 months the mean decrease in IOD was 5.8 mm Hg, the mean increase in C was 39%. The rate of success after 30 days was 77.4%. IOP and C showed statistically significant changes. The problems with determining C and the causes of the fluctuation of C during our follow-up are discussed. PMID- 1583838 TI - [Therapeutic possibilities in lens opacity after silicon oil tamponade]. AB - The most important complication of intraocular silicone oil is cataract formation. This leads not only to deterioration of the patients vision, but also to impairment of fundus visualisation. Preventing cataract formation by removing the silicone oil in the first postoperative weeks is hampered by an increased risk of redetachment. Furthermore, even with silicone oil vitreoretinal complications occur in up to 37%. Therefore if cataract surgery becomes necessary, it should be performed maintaining the silicone oil tamponade. The most suitable technique under this condition is phacoemulsification, avoiding damage to the posterior capsule and zonules. Due to this consideration we performed phacoemulsification with in the bag implantation of intraocular lenses in 13 eyes after silicone oil procedure. In no case intra- or postoperatively silicone oil was visible in the anterior chamber. Visual acuity improved in about 50% of the eyes despite of capsular fibrosis being present in all cases. Postoperatively YAG-lasercapsulotomy led to functional improvement in only one out of three eyes. PMID- 1583839 TI - [Eye manifestations of fetal alcohol syndrome]. AB - Alcohol is the most frequent and most important teratogenic agent causing mental and physical retardation in childhood. The alcohol fetal syndrome is characterized by pre- and postnatal growth retardation, hypotonia, hyperactivity, microcephalus, mental retardation and typical craniofacial malformations. The latter includes short palpebral fissures, a poorly developed philtrum, thin upper lip vermillion, short mandibles, a flattened midface structure and dysplastic ears. Ophthalmological signs occur in 90% and include epicanthus, ptosis, myopia, optic nerve hypoplasia and tortuous retinal vessels. Microphthalmus, coloboma and Peters' anomaly have also been described. Five children with alcohol embryopathy are presented. The histopathological findings of the enucleated eye of a 6th child with alcohol embryopathy which was sent to us for examination and which revealed an anterior staphyloma with Peters' anomaly is also described. Ophthalmologists should be aware of alcohol in pregnancy as a preventable cause of eye malformation. PMID- 1583840 TI - [Meningioma of the optic nerve sheath. Diagnostic problems despite use of modern imaging procedures]. AB - In spite of modern optical examination techniques such as sonography, nuclear magnetic resonance tomography (NMR) and x-ray computer tomography up to now the meningioma of the optic nerve sheath still poses a problem in respect of differential diagnosis. This problem is illustrated by two case reports. In both patients a meningioma of the optic nerve sheath could be diagnosed only after various attempts using all the imaging techniques mentioned above. NMR in combination with Gadolinium injection gave most important information. PMID- 1583841 TI - [Causes, surgical methods and results of primary management canaliculus injuries]. AB - A retrospective study of the results obtained from surgical treatment after canaliculus injuries during the period 1981 to 1987 at the Munich University Eye Hospital. The surgical treatment involved a ring intubation of both canaliculi with a silicone rod inserted with a pigtail probe (Kellnar probe). In 45 patients with an average follow up period of 2.1 years we found a 91% success rate with anatomical reconstruction of the injured canaliculus. Although the lacrimal passages were patent, 4% of these patients complained of epiphora. We analyse the circumstances of the injury, the age of the patient and complications. The discussion includes a review of relevant literature. PMID- 1583842 TI - [Acanthamoeba keratitis caused by extended wear contact lenses]. AB - A 68 year old female with aphakic soft lenses on an extended wear basis developed an Acanthamoeba-keratitis. The diagnosis could be confirmed by a positive culture of a corneal smear, the contact lens and the care solution. Immediate antibiotic therapy including aminoglycosides and cephalosporines topically showed response with clearing of the stromale infiltrates and, as a residuum, the development of small stromal scars at the former site of inflammation. An Acanthamoeba-keratitis should be considered in the differential diagnosis of all cases of keratitis in contact lens wearers that are unresponsive to topical medical therapy and without bacterial growth on routine cultures. PMID- 1583843 TI - [Bilateral optic neuropathy with papilledema]. AB - The findings in nine patients are presented who suffered from acute bilateral visual loss occurring within less than one week, and all showed optic disc edema. CT scans revealed no abnormalities and the CSF-pressure measured in 6 patients was normal. Four of the patients (22 to 53 years old) recovered completely under orally given prednisolone (about 100 mg/day). The recent history of three patients suggested that the optic neuropathy was associated with an infection. This parainfectious process may be identical to the bilateral optic neuritis described in children. Four older patients (55 to 63 years) did not respond to steroid therapy. Their vision did not significantly improve. They showed attenuated retinal arteries; therefore it can be assumed that ischemia plays a role in the pathogenesis of this second type of optic neuropathy. In none of the cases a toxic optic neuropathy could be confirmed. One patient who experienced a visual loss down to finger counting after throat-surgery without marked blood loss recovered partially after steroid treatment. PMID- 1583844 TI - [An instrument for projecting visual perception by monofocal and bifocal intraocular lenses]. AB - With the aid of a simple optical system similar to an astronomical telescope, images of spectacle lenses, contact lenses and intraocular lenses can be projected in front of, onto or into the eye. These optical images function like real lenses and enable their performance to be evaluated. In the case of intraocular lenses, visual perception through monofocal or bifocal lenses and teledioptric systems can be reproduced. PMID- 1583845 TI - [Qualitative analysis of the elasticity of the bovine cornea by holographic interferometry]. AB - Double-exposure holographic interferometry is used for deformation analysis of the surface of bovine corneas subjected to intraocular pressure increase. Reproducible individual fringe patterns are recorded for an intraocular pressure of 1340 Pa and subsequent pressure changes of 20, 40 and 80 Pa, respectively. These interference fringes characterize loci of equal displacement. In spite of interindividual variations of the central fringe pattern some basic types can be differentiated: round, oval, drop-like, double-centers, symmetrical as well as unsymmetrical and irregular forms. The peripheral fringe patterns of the cornea can be described by 3 basic types, even taking into account individual variations: circular, circular with an irregular component and irregular. The precision of the method allows to visualize minute local elasticity differences. Results of these investigations do not support the assumption, that the center of the cornea has a higher elasticity than peripheral regions in general. These elasticity differences between central and peripheral areas vary between individual corneas for small intraocular pressure changes at a basic pressure of ca. 10 mm Hg (1340 Pa). PMID- 1583846 TI - [Association of Rhein-Westphalian Ophthalmologists, 153rd meeting. Wuppertal, 11 12 May 1991. Abstracts]. PMID- 1583847 TI - [Reference values for apolipoproteins and HDL-2/HDL-3 in childhood]. AB - It is known from epidemiological studies, that high apolipoprotein B or low HDL-2 concentrations in serum are correlated with an increased risk for premature cardiovascular diseases. It was the aim of this study to generate reference values for apolipoproteins and HDL-cholesterol fractions to accomplish early diagnosis and therapy. All concentrations are age depending, being low at birth and increasing during the first years of life. This rise is more pronounced in apolipoprotein B than in apolipoprotein AI and HDL-2. Apolipoprotein II and HDL-3 reach later childhood values as early as at the end of the first month of life. The ratio of B and AI, which is a very good indicator for an increased risk for premature cardiovascular diseases, moves also distinctively upward during the first year of life. PMID- 1583848 TI - [Comparison of free amino acids in capillary and venous blood serum of children and adolescents with phenylketonuria and leucinosis]. AB - Concentrations of free amino acids were determined quantitatively by ion exchange column chromatography in serum from capillary and venous blood of children and adolescents with phenylketonuria (n = 38) and leucinosis (n = 3). Serum was deproteinised by 5% sulphosalicylic acid (1:1, v/v). The results showed with exception of aspartic acid, glutamine and glutamic acid a very close correlation. The correlation coefficients ranged from 0.849 to 0.996. It is concluded that serum from capillary blood can be used for screening of amino acid metabolism. PMID- 1583849 TI - [Follow-up of Spielmeyer-Vogt disease over 21 years]. AB - Spielmeyer-Vogt-disease (juvenile neuronal ceroid-lipofuscinosis, Batten's disease) is one of a group of severe inherited neurodegenerative disorders called neuronal ceroid-lipofuscinosis, being characterized by accumulation of ceroid lipofuscin within different organs of the body. A patient is described who developed visual, intellectual and motor deterioration as well as recurrent seizures during an observation period of 21 years. At the age of ten years vacuoles and "fingerprint-profiles" in lymphocytes and "fingerprint-profiles" beside "curvilinear bodies" in dermal cells lead to the diagnosis juvenile neuronal ceroid-lipofuscinosis. Clinical assessment of vision, intellect, language, motor function and epilepsy established a scoring system. The practicability of this scoring system is documented by the particularly poor clinical course of the disease over 21 years in our patient. Since there is no causal therapy the continuous care by the pediatrician for the whole family is of great importance. PMID- 1583850 TI - [Infection-induced pathologic change in respiratory parameters in the young infant]. AB - While many aspects related to the etiology and pathogenesis of sudden infant death remain unclear, the ultimate trigger event appears to be an acute regulatory disturbance of the cardiorespiratory neurons of the reticular formation of the brain stem. Retrospective studies have demonstrated that SIDS often occurs after infection of the upper respiratory tract. We present the case history of a 10-week old infant, where the respiratory pattern demonstrated highly pathological alterations induced by a mild infection of the upper airways, as confirmed by oxycardiorespirography. Oxycardiorespirography provides continuous recording of the respiration (transthoracic impedance) extending over several hours during sleep and during the critical phase just before going to sleep and waking up in relation to heart rate, partial oxygen pressure (measured transcutaneously) and nasal flow. The presented infant is a premature infant delivered in the 34th week of gestation according to Dubowitz (artificial respiration for 7 days due to hyalin membrane syndrome stage II). During infection periodic breathing was found to be 19.3% with partly severe hypoxemia. The longest single episode of apnea was 30 seconds. On the average, 5 episodes of bradycardia occurred (less than 100/min/measuring hour). An OCRG investigation performed at the age of 5 weeks and after disappearance of the infection at the age of 12 weeks yielded normal findings. This permits the conclusion that in out patient an infection of the upper airways may have induced a pathologic respiratory pattern, which could be a major trigger mechanism for sudden infant death. PMID- 1583851 TI - [Mediastinal cystic lymphangioma as a cause of hydrops fetalis]. AB - This report is upon a case with fetal hydrops on the base of a paracardiac cystic lymphangioma in the mediastinum. The newborn which had hypoplastic lungs and multiple pneumatothoraces died because of a pulmonary insufficiency. An overview is given about the most common causes of the nonimmune fetal hydrops, and the pathomechanisms are discussed. PMID- 1583852 TI - [Nephropathy gonadal dysgenesis--or incomplete Drash syndrome?]. AB - This is a report about a phenotypical normal girl with nephropathy and gonadal dysgenesis. At the age of 2 years 8 months she presented with steroid resistant nephrotic syndrome. Focal segmental glomerulosclerosis was found by biopsy. Because of delayed puberty karyotyping was performed, which revealed 46 XY. Thirteen years after onset of proteinuria she reached end stage renal failure. Gonadal dysgenesis and nephropathy are often indistinguishable from incomplete Drash syndrome. Children with early nephropathy of unknown origin or gonadal dysgenesis should be observed for development of Wilms tumor. When chronic nephropathies are present in girls, karyotyping should be considered. PMID- 1583853 TI - [New aspects in prevention of febrile convulsions]. AB - In general, febrile convulsions have a good prognosis. The risk of death or neurologic and mental handicap is low. Though the risk of epilepsy is increased, there is no evidence that anticonvulsant treatment can prevent occurrence of later epilepsy. The aim of anticonvulsive prophylaxis is reduction of the rate of recurrences of febrile convulsions. Recent results point against the assumption that these can be prevented by long-term anticonvulsive treatment with phenobarbital or valproate. An alternative for longterm prophylaxis is intermittent short-term rectal application of diazepam suggested for children with a hightened risk of recurrences. Long-term prophylaxis with phenobarbital should only be considered in a small number of selective children. PMID- 1583854 TI - [High dosage methotrexate in combination with "8 in 1" in therapy of pediatric grade III/IV brain tumors]. AB - 20 patients with malignant brain tumors in childhood were treated according to a regimen which included initial surgery, preradiation chemotherapy and subsequent irradiation. The chemotherapy consisted of alternating cycles of high-dose methotrexate (12 g/m2) and "8 drugs in 1 day" (Bleyer, 1983). Each cycle was to be given up to six times, as tolerated. The diagnoses were medulloblastoma in 10 cases, astrocytoma in 5 cases, ependymoma and PNET in 2 patients each, and malignant mesenchymoma in 1 case. 15 patients were previously untreated, 5 patients experienced relapse after a different first line therapy and a longer time interval. 8 patients are in continuous complete remission for 13 to 54 months. The toxicity upon the bone marrow, the kidney and the inner ear was tolerable. Long lasting emesis contributed a marked problem to the patients but did not cause abbreviation of the therapy. The neurotoxicity was notably mild. Three episodes of generalized seizures were seen without subsequent sequelae, four cases of peripheral neuropathy were attributable to vincristine. A leukoencephalopathy was neither detected on clinical grounds nor on neuroradiological imaging. Therapy related deaths were not seen. We conclude that the combination of HD-MTX and "8 in 1" markedly contributes to the intensification of the chemotherapy for malignant brain tumors in childhood. In the setting as preradiation chemotherapy the toxicity is tolerable. PMID- 1583855 TI - [Diagnostic possibilities and limits of 4-electrode rheoencephalography in premature infants with risk of brain damage]. AB - Diagnostic value of cerebral electrical impedance for recognizing the risk of cerebral damage was analysed in 63 premature infants with postnatal respiratory disturbance during the first 4 weeks of life. Relationship between clinical risk factors like gestational age, Apgar scores, blood gas values on the one hand and impedance parameter of pulse volume, flow velocity and periphereal vascular resistance on the other were studied by means of correlation as well as variance analysis. Decrease of gestational age, Apgar score and increasing severity of respiratory disturbance cause statistically significant lowering of impedance parameters indicating reduction of volume, flow velocity and periphereal resistance in cerebral circulation by extreme immaturity, serious asphyxia as well as idiopathic respiratory distress syndrome. On contrast no statistically significant difference could be found between infants with and without intraventricular haemorrhages. However, significant differences were seen between group of patients only. Because of intercorrelation of risk factors and distinct variance no critical level of impedance parameters could be defined for the individual patient. PMID- 1583856 TI - [The Graz SIDS Risk Questionnaire: I. Development and validation]. AB - Based on the results from semistructured interviews with parents of fifty SIDS victims and of fifty matched controls we developed a SIDS risk questionnaire, the so-called SRFB Graz. In a retrospective study this questionnaire was applied to 65 SIDS victims and 195 comparable controls. By statistical analysis a cut point was computed, which discriminates SIDS cases from controls with a sensitivity of 86% and a specificity of 95%. PMID- 1583857 TI - [The Graz SIDS Risk Questionnaire: prospective study of 6,000 infants]. AB - In a prospective study (1988-1990) the SIDS risk questionnaire SRFB was applied to 6000 infants born in the Department of Obstetrics, University Hospital Graz. In all infants at an increased statistical risk for SIDS a standardized intervention including pediatric and polysomnographic investigations was performed. As a result the SIDS incidence decreased from an average of 1.92 per thousand lifeborns (1984-1988) to 0.83 per thousand lifeborns (1989-1990) in our test group, which means a striking reduction of the SIDS incidence by 57%. In addition to this effect, the intensified information of parents and physicians about possible signs of an increased risk for SIDS lead to a general reduction of SIDS in Styria. PMID- 1583858 TI - [Children of drug-dependent mothers--personal experiences and review of the literature]. AB - The increasing incidence of drug abuse in central Europe leads to a growing number of children with intrauterine drug exposure. During pregnancy various risks affect these children. Postnatally severe symptoms of withdrawal are observed frequently. The psychosocial development is endangered. Between 1986 and 1990 30 drug dependent women attended the obstetric department of the University Hospital Basel during pregnancy. The data of 21 children born to mothers drug dependent at birth were evaluated. 11 children were born in 1990. 12 mothers received Methadon, 10 were polydrug abusers. Positive serology was found for hepatitis in 18, for HIV-infection in 9 women. 6 babies were premature, 8 were small for gestational age. 20 newborns presented withdrawal symptoms which required a mean hospitalization time of 45 days. Tonic and/or clonic seizures were observed in 6 neonates. In 9 other children some symptoms were suspicious of seizures. EEG recordings were pathological in 10 of 12 infants. For the control of withdrawal symptoms 16 children received pharmacological treatment for a mean duration of 61 days. Neurodevelopmental examinations were performed in 14 children at an average age of 22 months. Neurological findings were pathological in 2 children. 3 had mild, 2 had severe mental retardation, 5 presented with behavioural disturbances. Our data are compared with those of the literature. Therapeutic proposals for children of drug dependent mothers are presented. The impact of methadon programs on the exposed children is discussed. PMID- 1583860 TI - [Psychological stress in institutional geriatric nursing]. PMID- 1583861 TI - [Sexuality in the old age home]. PMID- 1583859 TI - [Homozygous alpha-1 antitrypsin deficiency (PiZZ) and bronchial asthma in childhood--is there a connection?]. AB - Ten children and adolescents (aged four to 21 years) with the homozygous form of alpha-1-antitrypsin deficiency (PiZZ) were investigated with regard to obstructive airway disease. Besides the recording of the history, tests of lung function and allergy tests were performed. It was shown that bronchial asthma occurred in three out of ten patients. However, we could not demonstrate any statistically significant increased incidence of bronchial asthma in our unselected PiZZ-patients compared to the overall population. There was no indication of emphysema in any of the nine patients. PMID- 1583862 TI - [Aggression in old age homes]. PMID- 1583863 TI - [The secretariat of the German Nursing Association in Berlin]. PMID- 1583864 TI - [Nursing. An interview with Ingrid Rehwinkel]. PMID- 1583865 TI - [Environmental hygiene in nursing education? III]. PMID- 1583866 TI - Carrier detection for Sjogren-Larsson syndrome. AB - Sjogren-Larsson syndrome (SLS) is an autosomal recessive disorder associated with reduced activity of the fatty alcohol: NAD+ oxidoreductase complex (FAO). Recent studies indicate that SLS patients are specifically deficient in the fatty aldehyde dehydrogenase (FALDH) component of FAO. To investigate the possibility of carrier detection for SLS, FAO and FALDH activities were measured in cultured skin fibroblasts from normal controls, obligate SLS heterozygotes, and SLS homozygotes using the 18-carbon substrates octadecanol and octadecanal. Three of 11 heterozygotes for SLS had FAO activities that were within the normal range; the other 8 SLS heterozygotes had FAO activities below normal. In contrast, fibroblast FALDH activity was more effective than FAO in discriminating SLS heterozygotes from normal controls. FALDH activity (nmol min-1 (mg protein)-1) in normal controls was 8.54 +/- 1.16 (mean +/- SD; range 6.95-10.77; n = 12) and in SLS heterozygotes was 5.12 +/- 1.31 (range 3.28-6.96; n = 11), or 60 +/- 15% of mean normal activity. One SLS heterozygote had an FALDH activity within the lower range of normal; this heterozygote had an FAO activity below normal. None of the SLS heterozygotes had an FAO or FALDH activity that was in the range of that measured in SLS homozygotes. These results indicate that measurement of FAO and FALDH activities in cultured skin fibroblasts using 18-carbon substrates is useful for SLS carrier detection. PMID- 1583867 TI - Maple syrup urine disease: interrelations between branched-chain amino-, oxo- and hydroxyacids; implications for treatment; associations with CNS dysmyelination. AB - Four patients with classical maple syrup urine disease were treated for up to 5885 days per patient with a relaxed protocol allowing branched-chain amino acid levels in plasma to rise about 5 times the normal mean value. The patients have had satisfactory development and lifestyle. They spent 318 days in hospital during 19,937 aggregate treatment days. Plasma levels of leucine and the corresponding 2-oxo acid were shown to be elevated disproportionately relative to the other branched-chain metabolites. Levels of isoleucine and valine were lower than those of leucine apparently because of runout into alternative metabolite pools, namely the R metabolites for isoleucine and the hydroxyacid for valine. The chronic accumulation of branched-chain 2-oxo acid(s) in our patients was associated with chronic dysmyelinating changes in CNS visible by imaging. Another patient with a thiamine-responsive variant of maple syrup urine disease had five acute crises incurring 29 days in hospital in a total of 6910 treatment days. However, she did not have chronic metabolic dyshomeostasis (her average plasma amino acid values were normal) and she had no evidence of dysmyelination. A relaxed treatment protocol for patients with maple syrup urine disease may benefit them in quality of life, but it apparently exacts a cost in metabolic control and CNS pathology. PMID- 1583868 TI - A synopsis of the unconjugated acidic transamination metabolites of phenylalanine in phenylketonuria. AB - We present blood and urine levels of unconjugated o-hydroxyphenylacetic, phenyllactic and phenylpyruvic acids in 61 children (2 years of age and above) and juveniles with phenylketonuria on or partially off diet. The samples were obtained during 185 scheduled outpatient visits and have been analysed with gas chromatographic methods. The compiled data define reference ranges of phenylalanine transamination capacity and of renal transport of metabolites which may be of value in further studies on the pathogenesis of phenylketonuria. PMID- 1583869 TI - Leucine and tissue distribution of bulky and small neutral amino acids in rats: dissociation between transport and insulin-mediated effects. AB - The mechanism of the observed decrease in the plasma concentration of several amino acids in the presence of high levels of Leu has remained unexplained. In the present study a decrease in the plasma concentration of Ile, Val, Phe, Tyr, Met, Ala, Pro and Gly was observed after the intraperitoneal injection of Leu to weanling rats. Decreases in net intracellular concentrations in muscle accompanied the decrease in plasma of all of these amino acids except Pro and Gly. An increase in the distribution ratio muscle/plasma was observed exclusively for Gly after administration of Leu or of a non-insulinogenic transport system L analogue. Diazoxide suppressed the Leu-induced decreases in plasma and muscle intracellular concentrations of Ile and Val as well as of Pro in plasma. An increase in the distribution ratio liver/plasma was observed for Pro and Gly in the absence but not in the presence of diazoxide. All the above changes were statistically significant. Hence insulin probably mediates Leu effects, promoting an increased utilization of Ile and Val in muscle and of Pro in liver. A more direct effect of Leu appears to be involved in the apparent increased utilization of Phe, Tyr and Ala in the same tissue. Gly depletion in plasma can be explained by its trapping by inhibitory action of Leu on the exodus of Gly through transport system L. PMID- 1583870 TI - Alloisoleucine in isovaleric acidaemia. PMID- 1583871 TI - Renal tubular function of patients with classical Menkes disease. PMID- 1583872 TI - Continuous arteriovenous haemofiltration in a neonate with hyperammonaemic coma due to citrullinaemia. PMID- 1583873 TI - Animal models for lysosomal storage diseases: a new case of feline mucopolysaccharidosis VI. AB - Two long-haired Siamese cats are reported with clinical manifestations of human mucopolysaccharidosis VI (Maroteaux-Lamy disease): facial dysmorphia, dysostosis multiplex, paralysis. Urine of the two affected animals contained a high concentration of glycosaminoglycans, as detected by the dimethylmethylene blue test. Qualitative analysis, performed by thin-layer chromatography of the cetylpyridinium chloride-precipitable material, showed dermatan sulphate. Excessive incorporation of [35S]sulphate in the intracellular mucopolysaccharide of cultured fibroblasts and deficiency of arylsulphatase B in such cells indicate that these cats are affected by Maroteaux-Lamy disease. They should thus be considered the first European case of feline mucopolysaccharidosis VI. PMID- 1583874 TI - 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase deficiency; effect of chenodeoxycholic acid therapy on liver histology. AB - The second step in the pathway for synthesis of bile acids from cholesterol is catalysed by the enzyme 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase. Deficiency of this enzyme has been reported to produce cholestatic liver disease with progressive cirrhosis. Treatment with chenodeoxycholic acid led to clinical and biochemical improvement in one patient. We report a further child with this disorder who presented with prolonged neonatal jaundice followed by symptoms of malabsorption of fat-soluble vitamins. Bile acid replacement therapy resulted in clinical and biochemical improvement; it was also possible to demonstrate improvement in the histological appearance of the liver biopsy 4 months after commencing treatment. PMID- 1583875 TI - Erythrocytic uridine diphosphate galactose in galactosaemia. AB - An earlier claim of a deficiency of uridine diphosphate galactose in erythrocytes of galactosaemia patients was not confirmed. Enzymic techniques similar to those of the earlier investigators were used to determine not only the concentration of uridine diphosphate galactose but also the ratio of this concentration to the sum of the uridine sugar diphosphates (uridine diphosphate galactose and uridine diphosphate glucose). The values in erythrocytes of galactosaemic subjects were similar to those of non-galactosaemic children on a galactose-restricted diet and to those of normal adults. These results cast doubt on the claim of a major deficiency of uridine diphosphate galactose in galactosaemia and on the need for treating galactosaemic children with uridine. PMID- 1583876 TI - Storage material from urine and tissues in the nephropathic phenotype of infantile sialic acid storage disease. AB - We analysed urine and tissue specimens from two nephrotic infantile sialic acid storage disease patients (nISSD) for free and bound sialic acids in comparison to non-nephrotic ISSD patients (ISSD), patients with minimal change nephrosis (nControl) and normal controls (Control). No differences in the excretion of urinary free sialic acid could be detected between ISSD and nISSD urines. Sialyloligosaccharide fractions were only slightly elevated and of apparently normal composition. Owing to glomerular dysfunction, measurable quantities of protein-bound sialic acids were present in nISSD and nControl. In nISSD tissues, free sialic acid was elevated 18-100-fold above control and 3-12-fold above Niemann-Pick A (NPA) samples. The storage of membrane-bound sialic acid was slightly increased compared to control tissues, but equal to those from NPA, thus reflecting an unspecific increase of membranes due to lysosomal storage. According to these results no major biochemical differences were detectable between ISSD and nISSD. The nephrotic syndrome in nISSD could not be related to a general deficit in the sialylation of glycoproteins. Nevertheless, a cell membrane-specific alteration in sialoglycoproteins of glomerular cells might still be possible. PMID- 1583877 TI - Oligosaccharides accumulated in the bovine beta-mannosidosis kidney. AB - The phenotype of bovine beta-mannosidosis (beta-mannosidase deficiency), recently identified in Salers cattle, is similar to the caprine form of the disease (Abbitt et al., 1991). This investigation was designed to characterize accumulated kidney oligosaccharides in bovine beta-mannosidosis. Oligosaccharides were extracted from the kidney of an affected Salers calf and purified by chromatographic techniques. The amount of accumulating oligosaccharides in 1 g of wet tissue was about 21 mumol. Structures of derivatized oligosaccharides were characterized by high-performance liquid chromatography, mass spectrometry, methylation analysis and sequential exoglycosidase digestions. The major accumulating oligosaccharides were Man beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4GlcNAc. Oligosaccharides accumulating in minor amounts were Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc, Man alpha 1-6Man beta 1-4GlcNAc beta 1-4GlcNAc and Man beta 1-4GlcNAc beta 1-4Man beta 1-4GlcNAc beta 1-4GlcNAc. As in caprine beta mannosidosis, oligosaccharides with terminal beta-mannose residues and cleaved as well as uncleaved chitobiose linkages were identified in bovine beta-mannosidosis kidney. The accumulating oligosaccharides in tissue were thus identical in bovine and caprine beta-mannosidosis; however, the source of the novel oligosaccharides remains to be determined. PMID- 1583878 TI - Gonadal mosaicism in a family with adrenoleukodystrophy: molecular diagnosis of carrier status among daughters of a gonadal mosaic when direct detection of the mutation is not possible. AB - Adrenoleukodystrophy is a severe, X-linked neurological disease that has been shown to be linked to DNA markers from Xq28. We tested several families with these markers and, in one family, found two apparent recombination events between DXS52 and the disease. Expansion of the study to include other tests and several others markers from Xq28 led us to conclude that recombination probably had not occurred and that, instead, the mutation in this family had a mitotic origin and that the grandmother was a gonadal mosaic. For genes that have been cloned, it is often possible to demonstrate the presence or absence of a specific mutation in such families and to determine carrier status on that basis. This is not possible when the gene has not been cloned. We therefore describe a method that can be employed by a molecular diagnostic laboratory to discriminate between people who inherit the same RFLP haplotype, with or without the mutation, from a parent with gonadal mosaicism in diseases where direct gene analysis is not yet possible. PMID- 1583879 TI - Zellweger syndrome in a preterm, small for gestational age infant. AB - A preterm (gestational age 34 weeks), small for gestational age infant (birth weight less than P2,3) is described. Because of unexplained slightly disturbed liver function tests at age 2 months, extensive metabolic examinations were performed. Elevated blood levels of very long-chain fatty acids, pipecolic acid and abnormal levels of bile acid intermediates were detected, suggesting a peroxisomal disorder. The plasmalogen content of erythrocytes was decreased. Morphologically distinct peroxisomes were absent in the liver. In fibroblasts an accumulation of very long-chain fatty acids, decreased activity of acyl CoA:dihydroxyacetone phosphate acyltransferase and impaired de novo biosynthesis of plasmalogens was found. In summary, a mild variant of the classical cerebro hepato-renal syndrome of Zellweger was found without the characteristic clinical facial signs. PMID- 1583880 TI - Effect of methylmalonate on in vitro lactate release and carbon dioxide production by brain of suckling rats. AB - Methylmalonate (MMA) accumulates in the tissues of patients with methylmalonic acidaemia, who present severe neurological signs soon after birth and later mental retardation. Attempting to understand the pathophysiology of the disorder, we investigated the effects of MMA on brain glucose uptake, lactate release and CO2 production. Glucose uptake and lactate release were studied by incubating 40 microns wide brain prisms from 15-day-old rats in Krebs-Ringer bicarbonate buffer, pH 7.0, containing 5.0 mmol/L glucose and one of three concentrations of MMA (1.0, 2.5 and 5.0 mmol/L). Controls did not contain MMA in the incubation medium. MMA induced a significant increase of lactate production in a dose dependent pattern that was proportional to glucose uptake by the brain prisms. We also studied the influence of MMA on brain CO2 production from [2-14C]glucose and [U-14C]acetate by incubating brain prisms in the same buffer in the presence of the substrates with (experimental groups) or without (controls) 5.0 mmol/L MMA. MMA significantly reduced CO2 formation from both substrates. PMID- 1583881 TI - Quantification of N-acetyl-L-aspartic acid in urine by isotope dilution gas chromatography-mass spectrometry. AB - A method for quantification of N-acetyl-L-aspartic acid by isotope dilution gas chromatography-mass spectrometry using 15N-[2H3]acetyl-L-aspartic acid is described. The method is sufficiently sensitive to be used with solvent extraction techniques commonly employed for urinary organic acid analysis. The mean concentration of N-acetyl-L-aspartic acid in 80 normal and abnormal control urine specimens was 19.7 +/- 10.8 mg/g creatinine (12.7 +/- 7.8 mmol/mol creatinine). Seven patients, ages 9 months to 7 years, with Canavan-van Bogaert syndrome had urinary N-acetyl-L-aspartic acid levels from 606 to 4760 mg/g creatinine. The method can also be used with cerebrospinal fluid, in which the concentration of N-acetyl-L-aspartic acid is about one-tenth of that in urine. PMID- 1583882 TI - Cancer, chromosomes, and genes. PMID- 1583883 TI - Temporal lymphoreticular changes caused by ts1, a paralytogenic mutant of Moloney murine leukemia virus TB. AB - Inoculation of newborn FVB/N mice with ts1, a mutant of Moloney murine leukemia virus TB, induced severe thymic atrophy, spongiform polioencephalomyelopathy, and fatal posterior paralysis of the affected mice 35-40 days after inoculation. During the early course of infection viral replication was found in the spleen and, more importantly, within the thymus. Of these organs, the thymus was affected most severely by ts1-infection. Thymic weights of infected mice decreased markedly during disease progression, culminating in severe atrophy at the time of paralysis. During the first 10 days after inoculation, the virus replicated within the endothelial lining of splenic and thymic capillaries and was released albuminally into the basement membrane before spreading outwardly into perithelial, epithelial, and reticuloendothelial cells. Within these cells there was productive viral replication and subsequent dissemination of the virus to the thymic T cell population. Early infection (up to 10 days after inoculation) of the thymus induced an increase in thymocytic mitosis, followed by a progressive increase in thymocytic death between 15 and 35 days after inoculation. Thymuses from paralyzed mice killed 30-39 days after inoculation, demonstrated pronounced involution, characterized by loss of lobular architecture, effacement of the cortex and medulla, severe depletion of thymocytes, and partial or complete loss of Hassall's corpuscles. Immunohistochemistry for viral antigens showed positive labeling of splenic megakaryocytes, reticuloendothelial cells, and thymocytes in mitosis, and reticulo-epithelial-endothelial cells of the thymus. The thymic phase of viral replication appeared to be crucial for development of neurological lesions and posterior paralysis. PMID- 1583884 TI - Histopathologic and immunohistochemical changes in gut-associated lymphoid tissues after treatment of rabbits with dexamethasone. AB - Corticosteroids cause impaired cell-mediated immunity which may encourage development of gastrointestinal and respiratory infections. In order to better understand the effects of corticosteroids on gastrointestinal immunity, immunological and histological changes in gut-associated lymphoid tissues were examined after intravenous administration of dexamethasone to rabbits. In treated animals, lymphoid domes and follicles were considerably reduced in size, and the dome epithelial layer was markedly depleted of M cells and lymphocytes. There were numerous open lesions at the luminal surface of dome epithelium, consistent with necrosis of M cells, and a striking depletion of follicular B cells in treated animals. These immunologic and histologic effects of corticosteroids could have found profound, deleterious effects on mucosal immune responses and host resistance to microbial infections. PMID- 1583885 TI - Genomic organization and lack of transcription of the nicotinic acetylcholine receptor subunit genes in myasthenia gravis-associated thymoma. AB - To investigate the relationship between anti-acetylcholine receptor (AchR) autoimmunity and the occurrence of thymoma in a particular group of myasthenia gravis (MG) patients we analyzed DNA and RNA from MG-associated thymomas and control tissue by Southern and Northern blotting, respectively, using the AchR alpha, beta, gamma, delta and epsilon-subunit cDNAs or oligonucleotides as probes. Restriction analysis of genomic DNA showed an organization of AchR subunit genes in thymomas identical with that of normal tissues. In particular, in thymomas, there was no deletion of exon 4 of the alpha-subunit which encodes the main immunogenic region of the AchR. Dot and Northern blot analysis did not reveal transcription of any AchR subunit gene in thymomas. Instead, an RNA nucleotide sequence was identified in MG-associated thymomas that hybridized to an AchR oligonucleotide probe coding for amino acids 371-378 of the AchR alpha subunit. With this sequence as a probe, three DNA restriction fragments in addition to a restriction fragment of the AchR alpha-subunit gene could be identified in the human gene. The findings suggest that proteins with extensive homology to the AchR are not expressed in MG-associated thymomas. However, there are three genomic loci in thymoma genomes with a very restricted homology to the AchR alpha-subunit gene. One of these loci might code for the cross-reacting AchR epitope detected in almost all MG-associated thymomas in contrast to thymomas without MG. PMID- 1583886 TI - Antibodies defining rat endothelial cells: RECA-1, a pan-endothelial cell specific monoclonal antibody. AB - We have been searching for antibodies reactive with rat endothelial cells. Two monoclonal antibodies (mAb), named RECA-1 and RECA-2 were produced and tested in immunoperoxidase staining on frozen sections of various rat tissues. Staining patterns were compared to those obtained with the mAbs OX-2, OX-26, OX-43, and the polyclonal antibody to von Willebrand Factor (vWF), which all have been described to react with rat endothelial cells. The RECA-2 mAb showed staining patterns similar to those obtained with OX-2. RECA-1 showed to be the only antibody reactive with all vascular endothelium in the tested tissues. In addition, RECA-1 was endothelial cell-specific whereas all other antibodies crossreacted with one or more other cell types. No reactivity of RECA-1 was found in various tested species other than rat. The RECA-1 antibody was successfully applied in staining of paraformaldehyde fixed, plastic embedded tissue material. Immunofluorescence staining of viable endothelial cells demonstrated that RECA-1 recognizes a cell surface antigen. This was supported by intravenous injection of RECA-1, which showed the antibody to localize along the endothelium lining the vasculature in various organs tested. No reactivity of the antibody was seen when applied in immunoblotting of PAGE-run lysates from endothelial cell cultures and stromal cell preparations. We believe RECA-1 to be a promising antibody for rat endothelial cell studies, and in particular for further defining nature and function of endothelial cell-specific antigens. PMID- 1583887 TI - Serum factor that blocks the action of fish oils on endothelial cell production of platelet-derived growth factor is ceruloplasmin. AB - The production of growth factors by endothelial cells (EC) and other vascular cells may regulate the migration and proliferation of smooth muscle cells in normal and pathological vessel wall processes. We have previously shown that EC production of platelet-derived growth factor-like protein (PDGFc) is regulatable, and in particular is inhibited by specific lipids and by lipid-containing complexes, e.g. oxidized low density lipoproteins and fish oil emulsions. In this report we show that the inhibitory activity of the fish oils is in turn regulated by a component present in serum. Addition of the fish oil extract MaxEPA to bovine aortic EC, in serum-free medium, reduced PDGFc secretion to about 30% that of control cells. Addition of calf serum to the medium almost completely suppressed this inhibitory activity of MaxEPA, while in contrast, fetal calf serum augmented the activity. The suppressor activity in calf serum was dose dependent, with a half-maximal suppression of about 0.1% serum at a MaxEPA concentration of 50 micrograms/ml. Adult human serum was observed to have a quantitatively similar suppressor activity. The suppressor activity in human serum was identified as ceruloplasmin since: 1) purified ceruloplasmin also suppressed the activity of fish oil, and at concentrations comparable to the inhibitory levels in serum, and 2) removal of ceruloplasmin from human plasma derived serum by immunoprecipitation restored the inhibitory activity of MaxEPA. These results may have implications in the effectiveness of fish oils as a therapeutic agent for the reduction of intimal thickening in atherosclerosis. PMID- 1583889 TI - Polymerase chain reaction/sequencing analysis of ras mutations in paraffin embedded tissues as compared with 3T3 transfection and polymerase chain reaction/sequencing of frozen tumor deoxyribonucleic acids. AB - The efficiency of detection of H- and K-ras mutations in 27 CD-1 mouse liver tumors by direct sequencing of polymerase chain reaction (PCR)-amplified DNA isolated from formalin-fixed and paraffin-embedded tissues was compared with that after assay by both NIH 3T3 transfection (followed by sequencing of amplified transformant DNA) and direct sequencing of PCR-amplified DNA isolated from frozen tumors. Some tumor samples were chosen for comparison because they contained ras mutations that were detected by either NIH 3T3 transfection or sequencing of PCR amplified DNA derived from frozen tumors, but were not detected by both techniques. The efficiency of detecting K-ras mutations was similar for sequencing of amplified fragments derived from both paraffin-embedded tissues and from frozen tumors. However, these two techniques differed in their efficacy for detection of H-ras codon 61 mutations. Furthermore, this difference appeared to be mutation-specific: the sequencing of amplified products from paraffin-embedded tumor tissues allowed increased detection of CAA to AAA mutations but decreased detection of CAA to CTA mutations relative to sequencing of amplified fragments derived from frozen tumor DNA. Direct sequencing of PCR products from paraffin embedded sections was more sensitive than NIH 3T3 transfection for detection of activated K-ras genes containing codon 13 mutations but less sensitive for detection of activated H-ras genes containing codon 61 mutations. In summary, direct sequencing of amplified DNA from either frozen tumors or formalin-fixed, paraffin-embedded tissues can be more sensitive than NIH 3T3 transfection for detection of codon 13-activated K-ras genes. However, it appears to be less sensitive than NIH 3T3 transfection for detection of certain activating H-ras mutations. Depending upon the questions being asked of the data, each of the methods can provide useful information about ras gene mutations in tumor samples. The apparent differences in sensitivities between the methods is not yet understood, but such differences should be considered in the analysis of data obtained when only one method is used. PMID- 1583888 TI - Glomerular cells, extracellular matrix accumulation, and the development of glomerulosclerosis in the remnant kidney model. AB - Expansion of the mesangial extracellular matrix (ECM) with subsequent glomerular sclerosis is a prominent finding in most progressive renal diseases. To investigate the chronology of accumulation of ECM components as it relates to previously described cellular events, biopsies were obtained from rats at various times following 5/6-nephrectomy as well as from sham-operated controls. The biopsies were stained with PAS as well as immunostained for PCNA (a cell proliferation marker), monocytes/macrophages, types I and IV collagen, laminin, s laminin, fibronectin, heparan sulfate proteoglycan and entactin/nidogen. Immunostaining of biopsies obtained from 5/6 nephrectomized rats demonstrated an early glomerular cell proliferation, peaking at week 2. Expansion of the glomerular tuft area with rare glomeruli demonstrating focal sclerosis were also seen at week 2. Glomerular macrophage influx correlated with later ECM expansion and glomerulosclerosis. A progressive accumulation of all ECM proteins investigated was noted in the pathological mesangial matrix at week 2 and later time points. Northern analysis of total glomerular RNA at weeks 2 and 6 after 5/6 nephrectomy showed de novo expression type I collagen mRNA as well as small increases of glomerular mRNA levels for type IV collagen (1.2- and 1.4-fold over control RNA) and laminin (1.3- and 1.5-fold) but not s-laminin (1.1- and 0.9 fold). We conclude that cellular events including glomerular cell proliferation and macrophage influx are associated with increased gene and protein expression by ECM proteins in the remnant kidney model and may contribute to the development of sclerosis. PMID- 1583890 TI - Development and application of a radioimmunoassay for interleukin-8: detection of interleukin-8 in synovial fluids from patients with inflammatory joint disease. AB - A sensitive and specific radioimmunoassay for human interleukin-8 (IL-8) was developed using isotopically labeled homogenous natural protein. The detection limit (20% inhibition of 125I-IL-8 binding) was 30 pg/100 microliters; 50% displacement occurred at 140 pg/100 microliters. There was no cross-reactivity with the structurally and functionally related neutrophil-activating peptides 2 and 3 up to 500 ng/100 microliters. The intra- and inter-assay coefficients of variation were 4 and 7%, respectively. In vitro experiments showed that human fibroblasts triggered by interleukin-1, double-stranded RNA or virus release immunoreactive and biologically active IL-8 in a dose- and time-dependent manner. Monocytes produce immunoreactive IL-8 in the 100 ng/ml range when exposed to plant mitogen, bacterial endotoxin, virus or IL-1. Although the radioimmunoassay was more sensitive than the chemotaxis assay (detection limit 0.6 ng/ml versus 10 ng/ml) a correlation between concentrations of immunoreactive IL-8 and neutrophil chemotactic activity in the supernatants from stimulated monocytes and fibroblasts was observed. In synovial fluids from patients with inflammatory joint disease, IL-8 was clearly demonstrable, but there was no correlation between IL-8 levels and general parameters of disease activity (erythrocyte sedimentation rate and serum levels of C-reactive protein). Synovial fluids from patients with rheumatoid arthritis, seropositive for rheumatoid factor, contained significantly higher concentrations of IL-8 than synovial fluids from seronegative rheumatoid arthritis patients and patients with non-rheumatoid arthritis joint inflammation. There was a highly significant correlation between IL-8 levels and serum titers of rheumatoid factor. These findings suggest that the molecular mechanisms underlying joint inflammation may be distinct in different types of arthritis. PMID- 1583891 TI - Medical management and prevention guidelines for children with sickle cell disease. PMID- 1583892 TI - Pediatric ankle fractures. PMID- 1583893 TI - A case of polyuria. PMID- 1583894 TI - ANCA-positive glomerulonephritis. PMID- 1583895 TI - Radiology case of the month. PMID- 1583897 TI - Canadian system becomes U.S. bone of contention. PMID- 1583896 TI - Ongoing supervision of staff--a necessity. PMID- 1583898 TI - Detection of alcohol-related problems in general practice. AB - While primary care has considerable potential as a site for detecting and intervening for alcohol-related problems, few doctors currently identify these problems. The judgments of eight primary care physicians about alcohol-related problems in 371 of their patients were compared with the patients' responses to the Short Michigan Alcoholism Screening Test (SMAST) and the CAGE. The CAGE classified 11.4% of the patients as alcoholics and the SMAST identified 23.9% as probable alcoholics. However, the doctors identified only a small proportion (7.0%) of their patients as having any level of alcohol-related problem. The doctors did not identify 65.0% of CAGE-defined alcoholics and 82.3% of those patients classified by the SMAST as probable alcoholics. The discrepancy between primary care physician's judgments and the SMAST and CAGE may be attributable to the doctor's failure to identify patients with alcohol-related problems. An alternative explanation is that the SMAST and CAGE are inappropriate screening tools for use in Australian primary care. The findings are discussed in terms of the implications for training doctors and for the development of better measures of alcohol-related problems for use within a primary care context. PMID- 1583899 TI - Validity of self-reported alcohol consumption in the emergency room: data from the United States, Mexico and Spain. AB - The validity of self-reported alcohol consumption within 6 hours prior to injury based on breath-analyzer readings obtained at the time of emergency room (ER) admission is compared among probability samples of ER patients in Contra Costa County, California (n = 450), Mexico City (n = 500) and Barcelona, Spain (n = 864). The same questionnaire, study design and methods were used in all three countries to maintain comparability for comparative analyses. The analysis was restricted to those breath analyzed within 6 hours of injury occurrence who reported no drinking following the event. Validity of self-reports was high in all three samples. The proportion of those reporting not drinking prior to injury who had positive breath-analyzer readings was .5% in the U.S., 1.5% in Spain and 3.3% in Mexico. Validity of self-reports was not associated with cause of injury in the United States. In Mexico those injured in motor vehicle accidents or by violence were most likely to deny drinking, while in Spain those injured in violent situations were most likely to report not drinking. Validity of self reports in these studies is much higher than that found in other U.S. studies, but this may be partly due to the fact that self-reports were obtained after the patient had been breath analyzed. PMID- 1583900 TI - A genetic study of alcoholism in the Moscow population: preliminary findings. AB - This article reports the preliminary results of a family study of alcoholism in the Moscow population. A comparison of male and female alcoholic inpatients revealed differences between them in the patterns of alcoholism development and in the frequencies of the disorder among male and female probands' parents and siblings. Those differences, particularly those observed in the fathers of the female and male probands, may suggest that the liability and genetic predisposition to alcoholism in female alcoholics, on the average, are higher than those in male alcoholics. There were also differences between male and female probands in the frequencies of the types of drinking behavior (including alcoholism) we used to characterize individual phenotypes as to the liability to alcoholism in the probands' parents and spouses, indicating that the higher the liability and/or genetic predisposition to alcoholism the higher the probability of the proband's marriage to an individual with a higher liability to the disorder. The data on the comparison of the probands' children with their parents affectedness imply the possibility of a relationship between the genetic predisposition to alcoholism and the risk for mental and somatic disturbances in offspring of alcoholics. PMID- 1583901 TI - Person perception as a function of drinking behavior, gender and sex role stereotypes. AB - Gender and the level of drinking of the protagonist in a vignette were systematically varied to examine the effects of these variables on the inferences 400 undergraduates drew about the personal attributes and future of the character. Results showed that gender of the target did not significantly affect judgments about the protagonist, but perceptions of the character were strongly influenced by the alcohol-related behaviors attributed to him or her in the vignette. Evaluations of the protagonist generally became less favorable as drinking level increased. Abstainers were also viewed more positively than at least some comparison groups of drinkers on most measures. Although heavier drinkers were often stigmatized, they were also seen as having more fun. Subject gender, sex role attributes and attitudes toward women failed to influence judgments about the protagonists, but raters' own drinking habits did have an impact. Heavier drinkers showed a tendency to rate heavier drinking protagonists more favorably than did lighter drinkers. Implications of these results for prevailing theories about norms and evaluations affecting drinkers are discussed. PMID- 1583902 TI - Factor structure and correlates of the Tridimensional Personality Questionnaire. AB - Cloninger has proposed a model linking personality characteristics to patterns of responses to various stimuli, including alcohol. The model also uses personality characteristics to divide alcoholics into two types. In order to assess the relevant aspects of personality, the Tridimensional Personality Questionnaire (TPQ) was developed. This study examined the factor structure and correlates of the questionnaire to shed light on its validity. A confirmatory factor analysis of the TPQ failed to replicate the three proposed factors of novelty seeking, harm avoidance and reward dependence. Alternative models also failed to fit the data. The three factors were correlated with other personality measures theoretically linked to drinking (MacAndrew, Socialization and Sensation-Seeking scales), quantity and frequency measures of alcohol use and a measure of alcohol abuse (the Michigan Alcoholism Screening Test). The pattern of correlations provides evidence for the convergent validity of the TPQ. Nevertheless, the failure to replicate the factor structure suggests that the scale requires further revision before the model can be adequately tested. PMID- 1583903 TI - A modeling analysis of young drivers' judgments of accident risk due to alcohol use and other driving conditions. AB - Male (60) and female (60) college students who were under the legal drinking age completed a personal driving experience questionnaire and judged the probability of an accident occurring in 100 driving scenarios, half involving an intoxicated male driver and half a sober male driver. The scenarios also varied in terms of the safety levels of five other driving factors. Mathematical models derived from the probability judgments permitted measurement of the influence of the various driving factors on perceived risk. The driving factors in order of their influence on the accident probability judgments were driver intoxication nonintoxication, vehicle speed, road conditions, driver mood and driving experience, which did not significantly differ, and the driver's experience with alcohol use. Accident probability estimates of the alcohol scenarios increased as an additive function of the other driving factors, whereas increased risk of an accident in the no-alcohol scenarios was more dependent upon multiple unsafe factors. Female students judged the probability of an accident higher overall than did male students. Subject drinking classification (abstain-light, moderate or heavy) was not related to accident probability estimates. PMID- 1583904 TI - Long-term follow-up of behavioral self-control training. AB - Four samples of problem drinkers treated by behavioral self-control training were evaluated at 3.5, 5, 7 and 8 years following treatment, respectively. Of 140 cases, 99 (71%) were accounted for: 23 abstinent, 14 with controlled and asymptomatic drinking, 22 improved but still impaired, 35 unremitted and 5 deceased. Abstinent versus controlled-drinking outcomes were most strongly differentiated by pretreatment severity of alcohol problems and dependence and by the patients' pretreatment self-assessment and goals. Percentages of abstainers and of relapsed cases increased at long-term follow-ups. A reasonably constant percentage of known outcomes (14%) were clearly controlled and asymptomatic drinkers in each of the follow-up samples. Most of the long-term controlled drinkers had established this pattern within the first year following treatment. However, periods of controlled drinking during the first year did not reliably predict maintenance of this pattern. Successful asymptomatic drinkers were discriminable from other outcomes based on pretreatment characteristics. PMID- 1583905 TI - Genetic differences in psychomotor performance decrement after alcohol: a multivariate analysis. AB - We reanalyzed data on the decline in performance on a battery of psychomotor tests, after a standard dose of ethanol (0.75 g/kg body weight), of 206 same-sex twin pairs. Principal components analysis identified two orthogonal factors. The first factor was strongly associated with increased body sway, self-rated intoxication and unwillingness to drive, and reported low average weekly alcohol consumption, but showed a very weak association with blood alcohol concentration. The second factor had high loadings on tests assessing psychomotor coordination, was strongly associated with blood alcohol concentration, but was unrelated to willingness to drive or self-rated intoxication. Multivariate genetic analysis indicated independent genetic and environmental determination of differences in sensitivity to the effects of alcohol on these two factors. PMID- 1583906 TI - Alcoholic beverages in acute porphyria. AB - Alcohol consumption habits and the clinical consequences of intake of alcoholic beverages were examined in 254 individuals with a diagnosis of acute intermittent porphyria or variegate porphyria, using a questionnaire. The study failed to demonstrate a connection between the amount of ethanol consumed, or the frequency of ingestion, and the development of symptoms of acute porphyria, other than in extreme consumption patterns. It was concluded that agents in alcoholic beverages other than ethanol play important roles in precipitating the porphyric symptoms. A majority of the individuals were able to identify alcoholic beverages that were less well tolerated and those that were better tolerated. The results suggest that polyphenolic compounds and 3 to 5 carbon chain hydrophobic alcohols may be responsible for the induction of clinical symptoms in acute porphyria by some alcoholic beverages. On the basis of these findings advice is proposed on alcohol counseling in inducible porphyria. PMID- 1583907 TI - Ethanol inhibits interferon-gamma secretion by human peripheral lymphocytes. AB - Clinical and epidemiological evidence exists that subjects who chronically abuse alcohol are disposed to infections and certain types of cancer. In vitro inhibition of mitogen-induced lymphocyte proliferation has been shown suggesting a direct immunosuppressive effect of ethanol. Using human peripheral blood mononuclear cells we could demonstrate in vitro for the first time that even low ethanol concentrations of 6 and 12.5 mM significantly inhibit spontaneous and mitogen-induced secretion of interferon-gamma. This effect was more pronounced with lower mitogen stimulation and it increased in a dose dependent manner when higher ethanol concentrations were used. Inhibition of cell proliferation as measured by 3H-thymidine incorporation did not parallel the inhibition of interferon-gamma secretion. As this lymphokine exerts a great number of immunostimulating effects, diminished secretion might well contribute to the immune defect observed in alcoholics. PMID- 1583908 TI - The influence of age on supraoptic nucleus neurons of the rat: morphometric and morphologic changes. AB - Neurosecretory neurons (NSNs) of the supraoptic nucleus of 2-year-old rats presented significantly greater nuclear volumes and nuclear perimeters than those of 3-month-old animals. In aged NSNs, membranous bodies (MBs) were observed in the cytoplasm and the cell nucleus. The possible origin and function of these MBs are discussed. PMID- 1583909 TI - Aging, chronic administration of ethanol, and acute exposure to nitrous oxide: effects on vitamin B12 and folate status in rats. AB - Elderly patients with alcoholism often require surgery and receive nitrous oxide (N2O) as a component of their anesthetic. Since aging, ethanol, and N2O may all perturb folate and/or vitamin B12 metabolism, we examined the combined influence of these parameters on vitamin B12/folate status in a rodent model. Aged male Fischer 344 rats (24 months old) were given a liquid ethanol diet (35% of calories as ethanol) and control rats were pair-fed a liquid diet with carbohydrate substituting for the caloric content of ethanol. After receiving liquid diets for 7 weeks, rats were exposed to 60% N2O/40% 0(2) for 6 h. Urinary excretion of formic acid, formiminoglutamic acid (FIGLU), and methylmalonic acid (MMA) were used as indirect markers of folate/vitamin B12 status. In both the aged ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N2O exposure and returned towards background values by the second day. No changes occurred in MMA excretion. Exposure to N2O decreased methionine synthase activities in liver, kidney and brain, and recovery of methionine synthase activities occurred over a period of 4 days in both the aged ethanol-fed and control groups. Ethanol treatment for 7 weeks combined with acute exposure to N2O did not deplete the aged rats of folate or vitamin B12 in blood, liver, kidney or brain. Thus, in this animal model, aging, chronic ethanol administration, and acute N2O exposure did not act synergistically to produce prolonged and severe disturbances in folate and vitamin B12 metabolism. PMID- 1583910 TI - Chromosomal alterations and sister chromatid exchanges induced by zirconium oxychloride in human lymphocytes in vitro with relation to age of donors. AB - Aqueous solutions of zirconium oxychloride were added to human peripheral blood lymphocyte culture. Cultures were set up from healthy donors of both sexes belonging to age groups of 0-10, 11-20, 21-30, 31-40, 41-50 and 51-60 years. Airdried Giemsa schedule was followed for preparation of chromosomal aberrations and micronuclei count. Flourescence plus Giemsa staining techniques were applied for the study of sister chromatid exchange. The endpoints screened were chromosome and chromatid breaks, dicentrics and rearrangements. The frequencies of chromosomal aberrations and sister chromatid exchanges induced were compared between the samples of different age groups. The frequency of CA could not be related to age of the donor. However, the frequency of SCE increased with increase in age of female donor. PMID- 1583911 TI - Methylated cytosine level in human liver DNA does not decline in aging process. AB - In order to ascertain a generality of the age-dependent decrease in DNA methylation level among different mammalian species, methylated cytosine contents in human liver and spleen DNA at different ages have been determined using high performance liquid chromatography (HPLC). Unexpectedly, the liver DNA revealed no appreciable decline with age while the spleen DNA showed a slight reduction. It indicates that a decrease of methylation level in genomic DNA is not a common denominator of age-related changes in mammals. PMID- 1583912 TI - Plasma vasopressin and cortical nephron function in aging rats. AB - The role of vasopressin and Henle's loop transport in age-related polyuria and decrease in urine osmolality was investigated in female WAG/Rij rats free of kidney disease. In these animals, urine osmolality dropped from 2000 mosmol/kg H2O to 1000-1200 mosmol/kg H2O between 10 and 30 months, and urinary volume increased in proportion. Vasopressin concentration measured in plasma withdrawn from conscious, unrestrained, chronically catheterized rats was not significantly different in 10, 20 and 30-month-old animals (mean values 2.5 +/- 0.7, 2.2 +/- 0.2 and 2.0 +/- 0.3 pg/ml (n = 8), respectively). This suggests an impaired responsiveness of old kidney to antidiuretic hormone. The possible involvement of Henle's loop in this defect was studied by micropuncture. Paired collections of tubular fluid were done in the early distal and late proximal convolutions of the same cortical nephrons. Single nephron filtration rates did not significantly differ with age. Tubular fluid osmolalities in the early distal convolution were 165 +/- 13, 178 +/- 9 and 160 +/- 11 (n = 14) mosmol/kg H2O in 10-, 20- and 30 month-old rats, indicating similar diluting capacity of the cortical thick ascending limb. The amount of sodium transported from lumen to peritubular space by Henle's loop was also unchanged with age as were water, calcium, magnesium and potassium reabsorptions. These data indicate that the age-related decrease in urine osmolality is not related to either a significant reduced vasopressin plasma concentration or an increased single glomerular filtration rate or a reduced transport capacity of Henle's loop of the cortical nephron. Rather they suggest an impaired response to vasopressin of other segments of the nephron that is, the medullary thick ascending limb of Henle's loop and/or the collecting duct. PMID- 1583913 TI - Age-related changes in serotonin-immunoreactive neurons in the rat nucleus raphe dorsalis and nucleus centralis superior: a light microscope study. AB - Comparison of serotonin-immunoreactive (SER-IR) neurons in the nucleus raphe dorsalis (NRD) and the nucleus centralis superior (NCS) of 3-month-old and 28 month-old rats was made using qualitative and quantitative immunohistochemical analysis. Significant age-related changes in size and density of the SER-IR somata as well as in the length and number of their processes were demonstrated. A different vulnerability of the SER-IR neurons in both raphe nuclei to aging was observed that may be related to their different structural and functional features. PMID- 1583914 TI - Regulation of calcium levels in brain tissue from adult and aged rats. AB - The possibility that regulation of Ca2+ levels in brain nerve terminals is altered as the brain ages was examined in synaptosomes from adult and aged Fischer 344 rats. Free intrasynaptosomal [Ca2+]i was monitored with fura-2 as synaptosomes were depolarized with KCl, veratridine and ibotenic acid. With all three depolarizing agents, synaptosomes from aged animals reached higher free Ca2+ levels, and the maximal Ca2+ increases (delta Ca2+) estimated from computer assisted-fitting of the curves, ranged from 35% to 80% greater in synaptosomes from aged animals. The total Ca2+ content of the brain and of synaptosomes was also found to be considerably higher in aged than in adult animals. These results suggest that the aging process in brain is accompanied by alterations in both dynamic aspects of Ca2+ handling in nerve endings and the overall content of Ca2+ in the brain and synaptic terminals. PMID- 1583915 TI - Age-dependent alteration in regional cerebrovascular permeability during drug induced epilepsy. AB - Age-related changes in blood-brain barrier permeability were investigated during pentylenetetrazol-induced seizures in rats aged from 15 days to 120 days. Tracers such as [14C]sucrose and [3H]inulin which diffuse very slowly across the intact endothelium were simultaneously injected i.v. in rats treated with pentylenetetrazol (PTZ) or in control animals. Permeability-surface area products (PA) were determined in 9 brain regions. Pentylenetetrazol-induced seizures caused a significant increase in PA for both sucrose and inulin in all brain regions studied. Blood-brain barrier dysfunction was present only in animals in which the mean arterial blood pressure rose at seizure onset. Although increased blood-brain barrier permeability was found partly in similar areas in both young and adult rat brains, in adults the increase was the highest in the preoptic area, septum, colliculus inferior, hypothalamus and in the cerebellum while the increase was comparatively much smaller in the same areas of young brains. The increase in blood-brain barrier permeability was extremely high in the hippocampus, hypothalamus and cerebellum of 15-day-old rat brain and, was least affected in the corpus striatum and cerebral cortex in contrast to older rats. From the results obtained it may be concluded that the increased cerebrovascular permeability induced by pentylenetetrazol differs markedly in localization in young and adult rats. The age-dependent increased blood-brain barrier integrity is not over all dependent on variations in the blood pressure, but rather on progressive maturation of capillaries and changes in their internal structure, and local phenomena in neuronal activity during the seizures. PMID- 1583916 TI - Studying outcomes and hospital utilization in the elderly. The advantages of a merged data base for Medicare and Veterans Affairs hospitals. AB - That veterans aged 65 years and older are eligible to receive care either in the Veteran Affairs (VA) health care system or in the private sector under Medicare confounds the analysis of veterans' health services utilization and outcomes in two ways. First, changes in eligibility or financial barriers to access with regard to either system influence veterans' decisions about where to seek needed care. Second, analyses of VA care for elderly veterans that rely solely on VA data sources underestimate both overall utilization and treatment complications. Similarly, failure to consider the contribution of health care delivery in the VA system may confound analyses of health care utilization by the Medicare-eligible population. To study the magnitude of such confounding influences, we linked the Medicare and VA health care administrative databases for residents of New England and New York. Results indicated that, for ten surgical procedures commonly performed in the elderly, as well as for hospitalizations resulting from acute myocardial infarction and hip fracture, VA patients receive from 17.6% to 37.4% of hospital care outside the VA system. Private hospitalizations account for 5.5% to 19.5% of the care received by veterans within 6 months after an initial episode of care in a VA hospital. It was also found that initial hospitalizations for study conditions in the VA accounted for 3.6% of all such hospitalizations among elderly Medicare-eligible men. Although overall hospital utilization appears to be underestimated in VA data sources, it was found that ascertaining mortality from sources available within the VA produced excellent results when compared with deaths recorded in the Medicare enrollment files. A national, merged VA-Medicare data base is feasible and would enhance the validity of analyses of health care delivery both for elderly veterans and for the Medicare population. PMID- 1583917 TI - Identification of health status dimensions in a working-age population. An exploratory study. AB - With regard to health care there is a growing demand for comprehensive and reliable instruments of general health status measurement. In the Finnish Healthy Village Study, 427 men and 366 women of working age participated in a comprehensive health examination that included more than 120 physical, psychological, and social health status variables. On the basis of minimum correlation values, 37 health status variables were chosen for factor analytic study. Principal component factor analysis with varimax rotation identified six dimensions of health status: physical functioning, emotional state, perceived health, anthropometric state and blood pressure, social functioning, and biochemical state. These six factors accounted for 46% of the total variance of health status variables. Health profile analysis of both men and women revealed the same dimensions but in different order. Men ranked their self-rated general health more closely with their physical functioning, whereas women ranked it with perceived health. The identification of general health status dimensions has implications for planning health promotion programs and evaluating their outcomes. PMID- 1583918 TI - Patients as reliable reporters of medical care process. Recall of ambulatory encounter events. AB - This study explores the reliability of a data source on the quality and content of care rarely used in studies comparing the performance of health care organizations, that is, patient reports obtained from surveys. Evidence of patient survey reliability and validity and report data on patient reporting accuracy were reviewed for ten events that may have occurred during an initial health assessment for new adult enrollees of a health maintenance organization (HMO). Reports of 380 patients obtained through telephone survey were compared with medical records. For chest radiograph, mammogram, and electrocardiogram (EKG), patient reports exhibited both sensitivity and specificity. For serum cholesterol test, patients proved to be sensitive but not specific reporters. For blood pressure measurement, stool kit, and rectal examination, false negative rates were low (less than or equal to 0.10); they were somewhat higher for breast self-examination instruction and pelvic examination (0.21 and 0.22, respectively). Only for testicular self-examination instruction did patient reports fail to confirm medical record documentation (false negative rate = 0.53). Multivariate analysis showed a small association between increasing patient age and decreasing confirmation. Gender did not affect reporting ability, and agreement did not deteriorate over a 2- to 3-month postencounter interval. Patient reports appear to merit greater use in comparative studies of technical quality of care. Key words: quality of health care; quality assurance; health care; ambulatory care; patient recall; patient reports. PMID- 1583919 TI - The effects of preferred provider options in fee-for-service plans on use of outpatient mental health services by three employee groups. AB - Descriptions of how preferred provider organizations (PPOs), offered as options to employees enrolled in fee-for-service plans, affected use of outpatient mental health services are provided. Data are from the RAND Preferred Provider Organization Study, which has a sample of employees who enrolled in fee-for service plans 1 year before and 2 years after a PPO option was offered by three employers in two U.S. sites. To study effects of the optional PPOs on access to mental health care, usage patterns among those who initially stated that they did or did not intend to use PPO providers were examined. By the end of the second post-PPO year, employees had a similar annual probability of having an outpatient mental health visit whether or not they initially intended to use PPO providers. However, during the first post-PPO year, there was a decrease in the probability of use for those initially intending to use PPO providers, relative to those who did not intend to do so, among employees who had no regular medical provider. To study effects of the PPO option on usage levels of mental health care services, users of mental health services who primarily visited PPO were compared with those who primarily visited non-PPO providers. Users who visited PPO providers had significantly lower levels of use, controlling for other factors, than those who primarily visited non-PPO providers. Therefore, despite lower cost sharing for services received from PPO providers, the PPO option appeared to lower outpatient mental health care costs while having no more than a transient effect on access. This study did not evaluate mental health outcomes. PMID- 1583920 TI - The utility of severity of illness information in assessing the quality of hospital care. The role of the clinical trajectory. AB - This research explored whether differentiating patients whose severity of illness worsened, improved, or remained the same over the hospital stay is a good screen for quality of care. The hypothesis was that substandard care is more likely to occur among patients who have worsened. Severity was measured using the Computerized Severity Index (CSI) and MedisGroups in 233 patients who had experienced acute myocardial infarction and 279 who had undergone coronary artery bypass graft who were admitted to four New England hospitals in 1987. Deaths and patients with discharge diagnoses indicating iatrogenic events and complications were oversampled. Potential quality problems were identified through explicit screening criteria applied by nurse researchers and implicit physician reviews. Acute myocardial infarction patients who worsened had higher rates of potential quality problems than other patients (CSI, P = 0.06; MedisGroups, P = 0.01). For the CSI, the 49.4% of patients who worsened captured 70.6% of the potentially substandard care; for MedisGroups, the 35.6% of patients who worsened also encompassed 70.6% of the problematic cases. For coronary artery bypass graft, results varied depending on how severity and quality were defined. The CSI performed better using implicit physician review to identify problematic care (P = 0.00), capturing 76.5% of substandard cases among the 41.6% of patients who worsened. In contrast, MedisGroups did better using explicit quality screens (P = 0.04), grouping 60.5% of the problematic cases among the 47.0% of patients who worsened. After removing in-hospital deaths from consideration, a worsening trajectory was generally associated with a higher fraction of potential quality problems among live discharges. This preliminary study suggests that examining changes in illness severity may be a useful screen for substandard hospital care, but its utility could vary by condition and by how quality problems are defined. PMID- 1583921 TI - APACHE-L: a new severity of illness adjuster for inpatient medical care. AB - A principal concern regarding Medicare's diagnosis-related group (DRG)-based prospective payment system is whether hospitals caring for more severely ill patients may be undercompensated for the services they provide. Research on possible inequities in hospital payment has been hampered by the absence of an objective, easily obtained, and valid measure of patients' severity of illness. Because laboratory data are objective and computerized in most of our nation's hospitals, a system utilizing such data, if shown to discriminate between patients of differing expected resource use, could prove most helpful in examining possible inequities in prospective payment system hospital payment. At a major teaching hospital, data were used from length of stay inlier patients in the 10 most frequent medical DRGs in the U.S. to develop and evaluate a severity of illness system called APACHE-L. APACHE-L uses the laboratory component of the original APACHE score. Whereas DRGs explained 20% of the variation in length of stay for the top ten DRGs, APACHE-L explained up to an additional 14% of the variation. For ancillary resource use, DRGs explained 10% of the variance, and APACHE-L explained up to an additional 15%. Diagnosis-related group-specific analyses demonstrated that the amount of resource use variance explained by APACHE-L varied widely depending on the DRG (from R2 = .00 for DRG 410, chemotherapy; to R2 = .38 for DRG 320, kidney and urinary tract infections, age greater than 17 years with complications or comorbidities). The APACHE-L score, which is objective and readily available in our nation's hospitals, shows considerable promise as a severity of illness adjuster for a subset of DRGs. PMID- 1583922 TI - Hospital costs of societal violence. Arizona 1989. PMID- 1583923 TI - High variation medical conditions as an explanation of regional and temporal differences in hospital utilization. PMID- 1583924 TI - Applications of health status assessment measures in clinical practice. Overview of the third conference on advances in health status assessment. AB - To what purposes can the measurement of health status and health-related quality of life in clinical practice be put? What success might be expected from such endeavors? What obstacles lie in the way of that success? This monograph reports on the proceedings of a conference (the third in a series on advances in health status assessment) convened to address those questions. It presents two papers concerned with barriers to and benefits of health status and quality-of-life measurement in clinical practice and another two on strategies for overcoming those barriers and exploiting the benefits; also included are papers on historical forces motivating the use of these measures, one special address on ethical issues, eight presentations on empirical research in clinical settings, several panel discussions, and four methods roundtables. A broad conclusion to be drawn from the conference proceedings is that good methods and tools for health status assessment are here and are being used in many ways, but mostly for purposes other than routine patient care. Enthusiasm for fostering the diffusion of assessment instruments into practice settings is real, but so are the doubts, particularly for clinicians "in the trenches" of everyday practice, that widespread understanding and use can be achieved easily or quickly. The challenge for the field is to be aware of and sensitive to the uncertainties and misgivings of those in clinical practice, to address those apprehensions through both formal research and practical tests, and to maintain the momentum of communication and collaboration carried forward by this third conference. PMID- 1583925 TI - Fostering the application of health status measures in clinical settings. Proceedings of a conference. September 12-14, 1991, Washington, DC. PMID- 1583926 TI - Ongoing assessment of health status in patients with diabetes mellitus. AB - In 1990, the Division of Endocrinology and Metabolism of Henry Ford Hospital established an Outcomes Management data base for patients with Type I and Type II diabetes. A first cohort of 117 patients completed a baseline and 6-month follow up assessment; a second cohort of 116 patients completed the baseline assessment. Assessment at each time point includes: the Short Form--36 Questions (SF-36) health status instrument; a set of clinical variables known as the Diabetes TyPE scale Form 2.2 abstracted from the medical record; and the physicians' ratings of patient's health status along the major dimensions of the SF-36. Success with both face-to-face and mailed administration of the SF-36 has been good, with response rates of over 85% using both methods. Comparison of patient and physician ratings of patient health status indicated a significant discrepancy on ratings of general health status, with physicians' ratings higher than those of patients themselves. "Tight" glycemic control (as measured by glycosylated hemoglobin) was associated with somewhat lower ratings on the various SF-36 dimensions for all patients in the first cohort and for Type I patients in the second cohort. However, this effect did not seem to be attributable to those features of a complex regimen used to achieve tight control, but rather reflected a complex combination of age, education level, and number of daily injections associated with achieving good control. PMID- 1583927 TI - Measurement of general health status of non-oxygen-dependent chronic obstructive pulmonary disease patients. AB - Chronic obstructive pulmonary disease is a prevalent condition causing a high level of disability, and it is one of the leading causes of death. To assess the general health status of moderate to severe Chronic obstructive pulmonary disease patients, we studied 76 male patients attending an outpatient hospital clinic who were not dependent on oxygen and who did not present bronchial obstruction reversibility. We assessed clinical status (dyspnea, six-minute walking distance) and functional respiratory impairment (spirometry, and blood gas analysis) of the patients and also asked them to respond to the Spanish version of the Nottingham Health Profile, a multi-dimensional generic health status measure. Patients scored especially higher than the general population (denoting more level of distress) in energy, physical mobility and sleep Nottingham Health Profile dimensions. The former two dimensions scores had a high correlation with dyspnea (respectively Spearman Rs = 0.60, and Rs = 0.64; P less than 0.01). High levels of sleep disturbances were found for patients reporting low or very low dyspnea level. Health status measurement (Nottingham Health Profile dimension scores) and functional respiratory impairment were not correlated. Results underscore the importance of measuring symptoms carefully when assessing these patients, whose health status is substantially affected by the Chronic obstructive pulmonary disease. They also suggest that it is relevant to assess sleep disturbances in these patients. PMID- 1583928 TI - Patient-based health status measures in outpatient dialysis. Early experiences in developing an outcomes assessment program. AB - This paper describes the initial development of a patient-based outcomes assessment program in an outpatient dialysis unit. This project presented four logistical and practical issues that are discussed in this paper: patient acceptance of quarterly administrations of a generic health status survey (the SF 36); timing of administration during dialysis session; respondent burden; and staff burden. Also discussed are three issues related to the clinical use of these assessments: medical record status of SF-36 data; use in clinical decisionmaking; and clinicians' responses to aggregate data from patient-based health status assessments. The investigation reported presents strong evidence of patient acceptance of the SF-36. Data collection problems reflected the nature of a busy dialysis unit, and most have been corrected. Considering functional status, the role functioning of dialysis patients is most adversely affected; among well-being measures, patients are most compromised by pain and lack of energy. Clinicians' reviews of these results point to the need for normative data, information about severity of primary and comorbid diseases, and knowledge of relationships between SF-36 scores and physiologic parameters to make clinical use of generic health outcome assessments. PMID- 1583929 TI - Forces motivating the use of health status assessment measures in clinical settings and related clinical research. PMID- 1583930 TI - Family violence and the evaluation of behavioral concerns in a pediatric primary care clinic. AB - The goals of this study were to determine 1) the prevalence of exposure to intrafamilial violence among children attending a pediatric primary care clinic; 2) the prevalence of psychosocial distress among mothers bringing their children to the clinic; 3) the extent to which pediatricians are aware of family violence and maternal distress among their patients; and 4) whether families reporting violence are more likely to report behavioral or emotional problems with their children. The study focused on 243 mothers and their children who made scheduled visits to an inner-city, hospital-based pediatric residents' continuity clinic. The children ranged in age from 6 months to 14 years, with 69% of the children 2 years of age or younger. Parents answered questions about their own and their child's psychosocial functioning, including a modified version of the Conflict Tactics Scale, an instrument used to measure the prevalence of intrafamilial violence. Physicians independently rated parent and child psychosocial health and the likelihood of violence in the family. Forty percent of mothers said their family in the past year had experienced at least one episode of the five most serious types of violence described on the Conflict Tactics Scale. Mothers reporting these levels of violence were more likely to report psychosocial distress in their own lives as well as those of their children. Furthermore, family violence predicted maternal concern for child behavior even after accounting for the increased maternal distress associated with violence. Physicians had difficulty predicting which mothers would report violence (sensitivity 27%, specificity 81%) or which mothers would report concern about child behavior and emotional health. The authors concluded that an instrument like the Conflict Tactics Scale might both add to physicians' awareness of family violence and help explain some parental concerns about the behavior or emotional health of apparently asymptomatic children. PMID- 1583931 TI - Assessing quality of life. Moral implications for clinical practice. AB - The purpose of this paper is to examine some of the moral implications for clinical practice of the move toward measuring or assessing quality of life. For purposes of this presentation, discussions of the good life or quality of life have at least two "conceptual" preconditions. First is biologic life; second is a minimum cognitive apparatus to attach meaning to life (or a capacity for self awareness). Quality of life measurement in clinical care has three principal uses: screening, monitoring, and decisionmaking. The paper discusses how increasing reliance on quality of life measures is potentially morally appealing in all these cases, but also how moral "downsides" may be created that should be recognized and confronted with appropriate moral constraints. PMID- 1583932 TI - Strategies for improving and expanding the application of health status measures in clinical settings. A researcher-developer viewpoint. AB - Health status instruments may be useful in clinical settings to screen for functional problems, monitor disease progression or therapeutic response, improve doctor-patient communications, assess quality of care, or provide case-mix adjustment for comparing other outcomes between patient groups. However, conceptual, practical, and attitudinal barriers have prevented their wider implementation. Aside from providing more data on how these measures influence the process and outcomes of clinical care, several strategies may help to improve and expand their application. Wider application would be promoted by training health care providers about the methods of health status assessment, their validity, and the available instruments; comparing newer functional measures and older scales with which clinicians are familiar (to make scores more meaningful); providing better data for the selection of instruments; and improving the responsiveness of these questionnaires to clinical changes. If health status measures are used in direct patient care, it is important to determine whether the goal is to screen for functional problems or to monitor patient changes over time. These different purposes may influence the selection of instruments, the types of patients targeted (e.g., based on age or diagnosis), and the frequency of patient assessment. Health status measures must be easily incorporated into the office routine, requiring that they be brief, easy to interpret, and not require complex training or scoring algorithms. In this setting, it may be helpful to provide clinicians not only with functional status scores, but with interpretations and recommendations about management or community resources to consider. The costs of health status measurement and data analysis will probably be borne by third-party payers, who must be persuaded of their utility. When health status measures are used for quality assurance, average scores for groups of patients should be adjusted for disease severity, comorbid conditions, demographic characteristics, socioeconomic status, and baseline health status. Furthermore, the sickest or most vulnerable members of a clinical population may be least able to provide valid health status information because of dementia, frailty, blindness, illiteracy, or inability to speak English. These patients may be of particular interest, and are likely to alter average health status scores for a population, so methods to assure complete ascertainment must be considered. PMID- 1583933 TI - Health status measurement. Implementation strategies. AB - The creation of valid instruments of health status measurement does not guarantee their use in the clinical setting. Traditional continuing medical education has not been shown to effect physician behavioral change. Examination of the literature on the dissemination of new technology underscores the need for the acceptance and use of new methods by local opinion leaders whose behavior serves as a model for their colleagues. Since health status measurement will require a new way of evaluating the patient visit and the creation of new provider behaviors, widespread implementation will require the recruitment of local clinical leaders to serve as spokesmen for reconsideration of office care procedures. Advocates of health status measurement should seize on a variety of opportunities to disseminate their work. Medical school curricula in courses such as physical diagnosis could expose different approaches to the patient encounter to a new generation of physicians in a fairly painless and seamless manner. Academic practice plans, by virtue of their increasing trend to centralization, could commit to patient-oriented data collection--if not for instructional purposes, then for the overall health of the delivery system. The instruction of nurses and paraprofessionals in the collection of these data could expand the measures and help drive the system when physicians are not embracing the technology. There is need to exploit the enhanced capacity of computer hardware and software in the service of efficient data collection and trend analysis of health status.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1583934 TI - Where do we go from here? Opportunities for applying health status assessment measures in clinical settings. PMID- 1583935 TI - Recent developments and future issues in the use of health status assessment measures in clinical settings. AB - This paper provides a broad overview of the assessment of health status in clinical practice in three parts. Yesterday: The nation has undergone a paradigm shift in health-related thinking. The former paradigm emphasized only disease; the new emphasizes health, functioning, well-being, and disease. Measures of health and disease have evolved to reflect the new paradigm. Many are designed for clinical settings, based on measurement science, and are relatively brief. These newer measures have been used to document the natural history of disease, evaluate treatment effectiveness, and improve clinical case management. Today: Two barriers block full-scale use in clinical settings. The first barrier involves the meaning and interpretation of health status scores. Patients' scores are influenced by several types of patient mix variables and the timing of measurements. Interpretation is enhanced by valid normative data displaying the variability in health status among homogenous patient groups. The second barrier is utilization and mainstreaming. It involves all of the issues associated with changing the day-to-day behavior of clinicians and providers' routine processes to facilitate routine use of health status measures in clinical settings. Tomorrow: In the next decade, the nation will attempt to overhaul the health care system. As it does so, it will struggle with many issues: 1) clarifying the true aim of health care; 2) standardizing measures of health across patients, providers, and settings to evaluate benefit; 3) establishing cause and effect among structural-input factors, care delivery processes, and health outcomes valued by society; and 4) determining if and when cost containment actions have adverse effects on health outcomes. In this context, the importance of interpreting change in health status has a central role. PMID- 1583936 TI - Methods for assessing condition-specific and generic functional status outcomes after total knee replacement. AB - Many assume that, relative to generic measures, condition-specific health measures are both more sensitive to the condition's severity and more specific because they are less affected by other conditions. We analyzed the sensitivity and specificity of the generic SF-36, condition-specific scales based on the SF 36, and condition-specific measures based on the Knee Society's Clinical Rating System in a study of osteoarthritis patients following knee replacement. As hypothesized, knee-specific role function and pain measures were more specific than generic measures among patients with other comorbid conditions, and less so among patients with only knee problems. Physical function scales of both types were equally specific. Clinical indicators based on x-ray and range of motion were only weakly related to all measures of function. PMID- 1583937 TI - The validity and relative precision of MOS short- and long-form health status scales and Dartmouth COOP charts. Results from the Medical Outcomes Study. AB - This study estimated the validity and relative precision (RP) of four methods (MOS long- and short-form scales, global items, and COOP Poster Charts) in measuring six general health concepts. The authors also tested whether and how precisely each method discriminated relatively well adult patients (N = 638) from those with only severe chronic medical (N = 168) and only psychiatric conditions (N = 163), as clinically defined. For comparisons between the well group and both medical and psychiatric groups, RP estimates favored long-form over short-form, multi-item scales, and favored multi-item scales over single-item global measures and poster charts. In relation to long forms, short-form multi-item scales achieved a median RP of .93; RP estimates for global items and poster charts were .81 and .67, respectively. Variations in RP across methods and concepts were linked to differences in the coarseness of measurement scales, reliability, and content (including the effects of chart illustrations). These variations in RP have implications for the interpretation of scores, the statistical power of comparisons between clinical groups, and the size of confidence intervals around individual patient scores. PMID- 1583938 TI - Measuring the outcomes of care for mental health problems. The case of depressive disorders. AB - To conduct effectiveness research in mental health, many nontrivial problems need to be addressed. A multidisciplinary expert panel designed an outcomes module for major depression and dysthymia to measure disease-specific outcomes, treatments routinely provided, and patient characteristics that influence treatment or its outcomes. The outcomes module was pilot-tested to evaluate its ability to identify a diagnostically homogeneous group of patients, to establish its reliability and validity, and to assess the feasibility of administering the module in a mental health setting. In a cohort of 40 patients, the module identified all 31 patients who had a research diagnosis of major depression or dysthymia (100% sensitivity), and 2 of 9 patients who did not have this diagnosis (77.8% specificity). The outcomes module measured key constructs accurately enough to discriminate between groups of depressed patients expected to differ, indicating positive construct validity. High rates of instrument completion supported the feasibility of using the module in specialty settings. Extensive efforts locating patients for follow-up will be needed to draw valid conclusions about treatment effectiveness. PMID- 1583939 TI - Relationship between health utility and psychometric health status measures. AB - This study examined the relationship between health utility and psychometric health status measures. Utility scores derived by standard gamble and categorical rating methods were also compared to determine if they produce equivalent preference scales. Health status and utility was assessed in 73 chronic renal disease patients with anemia (hematocrit less than or equal to 30) participating in a 48-week clinical study. Patient preferences for current health and three hypothetical states were assessed using standard gamble and categorical rating procedures. Standard gamble utility was related to home management (P less than .05); categorical rating utility was related to home management (P less than .05), energy (P less than .05), alertness behavior (P less than .05), social interaction (P less than .05), and life satisfaction scale scores (P less than .05). Only 25-27% of the variance in utility scores was explained by the health status measures. Standard gamble utilities were consistently higher than categorical rating values for end-stage renal disease with hemodialysis (P less than .0001) and severe anemia requiring blood transfusions (P less than .0001). Patient preferences for current health may be influenced in part by their functional status and well-being, risk aversion or risk-taking attitudes, and the cognitive evaluation processes involved in making judgments necessary for the measurement task, as well as their actual preferences. PMID- 1583940 TI - Benefits and obstacles of health status assessment in ambulatory settings. The clinician's point of view. The Dartmouth Primary Care COOP Project. AB - In the past decade physicians have identified the need to expand patient assessment to include global function and quality of life. During the same period, the busy clinic has evolved into the location where this assessment seems most appropriate. Integrating functional health assessment into a busy clinical practice is difficult because the necessary steps require time, thought, recording, and follow-up. Attention to the office ecosystem is very important before any patient care management method is introduced. The clinician must transform the results of health status screening into a specific functional diagnosis. The clinician has to understand the sensitivity, specificity, and predictive value of the measure for a preliminary diagnosis to be made. Often, additional measurements must be taken to establish a specific diagnosis. These steps encompass assessment linkage. Once the specific cause for the dysfunction is recognized, the clinician then has to determine the need for special resources. This is called the resource linkage. By following the steps outlined in this paper, the clinician should be able to overcome many obstacles for functional health status assessment in busy ambulatory settings. PMID- 1583941 TI - Benefits and obstacles for development of health status assessment measures in clinical settings. AB - Health status measures offer scientific, humanistic, and economic benefits for clinical medicine. The main problem is the many intellectual and pragmatic obstacles that block successful development of these measures. The inventory of such problems includes the following: definition of health; medical components of health status; who makes the choice about what to include and emphasize; attributes to be rated by patients or clinicians; indexes to be created from those attributes (including mega-variable indexes, global indexes, and oligo category indexes); different measurements of the same entity; and clinimetric problems in nonclinimetric models. Several solutions to these multiple, complex difficulties can be offered: 1) ensure that a specific purpose, focus, and setting are clearly identified for every health status index; 2) recognize that an off-the-shelf index with high statistical scores for so-called reliability and validity may not be pertinent for a given current situation in which it is to be used; 3) avoid indexes involving combinations of excessive numbers of variables; 4) let patients choose the most significant foci and components of the indexes; 5) seek greater communication and understanding among multidisciplinary collaborators, who may have many differences in the ethos and goals with which they approach the construction of health status indexes; and 6) recognize that the construction of suitable health status indexes is an outstanding challenge in basic scientific inquiry, and, in this spirit, support major alterations in the current ideology for conceptualization and funding of what is basic science in clinical medicine. PMID- 1583942 TI - Can patients use an automated questionnaire to define their current health status? AB - Patient management decisions rarely incorporate standardized health status assessments, since accurate and reliable measures are difficult and expensive to obtain. In prior research with various methods for obtaining health data from patients, it was found that physicians' acceptance of a method was improved if it provided an individualized printout. It was also determined that patients will readily complete a health status questionnaire on a computer when the computer does not look like a computer. Patients' acceptance was greatest when they were presented with a single line of large, pressure-sensitive buttons with which they could respond to questions about their health histories. Using such an instrument, the HealthQuiz, the current study found the same discrepancy rate (3%) between patients' responses to health questions presented on HealthQuiz and during interview as between their responses to questions asked during two separate interviews. Further, to ascertain health status, rules determined by an expert panel were applied to patients' responses to health questions presented on the HealthQuiz screen. It was found that the numerical health status derived from answers to the automated presentation of questions was similar to numerical health status derived by a physician after a patient-physician interview. PMID- 1583944 TI - The clinical Swiss army knife. Empirical evidence on the validity of IADL functional status measures. AB - To encourage the clinical use of functional status measures, tools have been developed that are shorter and easier to administer. This study was conducted to provide empirical evidence concerning the validity of instrumental activities of daily living (IADL) scales. Similar to previous findings, this study found that a 50-item questionnaire was suitable for patient self-completion. This scale also showed good reproducibility over a 2-week period, a unidimensional factor structure, internal consistency, predictable correlations with other health status measures, and the ability to distinguish formal service users from nonusers. On the other hand, the findings also clearly demonstrate that caution is warranted when choosing rating formats and scoring procedures, and when interpreting patient responses. Ratings of difficulty, nonperformance, and assistance received should not be assumed to be interchangeable nor to reflect underlying physical ability. A great deal of sample variability was found when the process validity, or the subjective meanings of these ratings was examined. Scalogram analysis also indicated that the assumption of hierarchical ordering is not justified. Based on these findings, minimal questioning, dichotomous responses categories, and aggregate scores are not recommended for discharge planning or monitoring individual patients. PMID- 1583943 TI - Self-report versus medical record functional status. AB - The importance of assessing functional status in the hospitalized patient is gaining recognition. However, the availability and accuracy of medical record functional status data are uncertain. We collected data on 2,504 patients greater than 65 years of age discharged alive. A personal interview conducted 2 days before discharge recorded the patient's self-reported ability to perform 5 activities of daily living scales. Medical record abstraction was used independently to determine ability to perform the same activities of daily living scales. Patients who required any human assistance to perform a function were considered dependent. Patients were also contacted after discharge to determine the site of posthospital care (28% discharged to a nursing home). The amount of missing medical record functional status data varied by function from 20% for bathing to 50% for dressing. Ten percent of patients had no medical record functional status documentation concerning any of the five functions. The prevalence of self-reported dependence at discharge varied by function from 24% for feeding to 93% for bathing. The total number of dependencies differed between the two methods (medical records, 2.3 +/- 1.9; self-report data, 3.2 +/- 1.5). There was exact agreement between the two methods on the total number of dependencies in 28% of cases and differences of greater than or equal to 3 in 20%. In a stepwise logistic model predicting discharge to a nursing home and adjusting for other relevant variables, the number of dependencies as determined by self-report and medical record data each remained significant (Odds Ratios = 1.6). Self-report and medical record functional status data differ substantially, and the medical record data remain independently associated with nursing home placement. Several possible explanations for this finding are explored. PMID- 1583945 TI - [Diagnosis of brucellosis in an endemic area. Evaluation of routine diagnostic tests]. AB - BACKGROUND: The use of classic methods of diagnosis of brucellosis was analyzed, particularly serologic methods whose use in endemic areas and risk groups has been questioned in the literature. METHODS: Prospective analysis of these methods was performed in a group of 171 patients suspected as having brucellosis proceeding from an endemic area, with progressions of risk and frequent antecedents of brucellosis. The results obtained were compared in 119 patients in whom brucellosis was confirmed (80 with positive cultures and 39 with clinic serologic diagnosis) and in 52 in whom the diagnosis was excluded. RESULTS: The hemocultures provided a sensitivity of 70% with a mean delay in growth of 13.6 days. The rise of Bengal test showed sensitivity of 95% and specificity of 75%. The most adequate cut-off point for seroagglutination was of 1/160 and for the Coombs test 1/320 with sensitivities of 93 and 92% and specificities of 97 and 100%, respectively. CONCLUSIONS: The routine serologic tests offer good results for the diagnosis of brucellosis in endemic areas upon use of adequate cut-off points and permitting therapeutic decisions to be taken prior to knowledge of the results of the cultures. The rose of Bengal test is valid for initial selection of this type of population. PMID- 1583946 TI - [Quality of life in arterial hypertension]. AB - BACKGROUND: Quality of life is a key issue for the consideration of hypertension therapy. However, reliable and sensitive evaluation methods are not available in Spain. To this end, a quality of life questionnaire has been elaborated, its yield has been evaluated, and the influence of hypertension and several associated variables on the quality of life has been assessed. METHODS: A questionnaire on quality of life consisting of 62 items was elaborated. Its final evaluation was divided in an overall value and in four subindexes related with anxiety, depression, side effects, and somatic complaints. It was applied to two groups of hypertensive patients, one from hospital care (n = 90) and another from primary care (n = 89), and to a control group (n = 76). RESULTS: Although both populations with hypertension were significantly different regarding age, sex, use of therapies, organic impact and blood pressure, they were overall similar in quality of life. However, quality of life was different from that in control group, which showed better indices. In the hypertensive population, sex, severity of hypertension, type of therapy or duration of the disease did not have any influence on quality of life. CONCLUSIONS: The overall similar quality of life in both hypertensive groups (in spite of the many significant differences in their descriptive features) and the different quality of life between hypertensive and normotensive individuals (in spite of the similitude of their demographic parameters) suggest that the diagnosis of hypertension has by itself a greater influence on the quality of life than several hypertension-associated variables. It has also been found that the method used was sensitive and valid. Therefore, the use of the quality of life questionnaire can be a useful instrument for the monitorization of hypertensive patients. PMID- 1583947 TI - [Longitudinal anthropometric study of patients treated with hemodialysis maintenance]. AB - BACKGROUND: Protein-caloric malnutrition occurs commonly in patients undergoing hemodialysis (HD) therapy and can be detected by several methods. METHODS: In this work, anthropometric techniques are employed to assess the nutritional status of 15 maintenance HD ambulatory patients. Measurements of weight, triceps skinfold thickness and arm muscle area were obtained and followed at 8 and 19 months. RESULTS: In the beginning, 70% of patients had body weight within normal limits, but 53% of them showed reductions in skinfold thickness, more strikingly in women, and 87% of male patients evidenced some degree of muscle wasting. Longitudinal data showed a tendency to fat depletion. CONCLUSIONS: These results point out the need of appropriate diets in these patients to avoid further deterioration in their nutritional status. PMID- 1583948 TI - [Current diagnosis of brucellosis]. PMID- 1583949 TI - [Diagnosis of catheter related infection, 15 years later]. PMID- 1583950 TI - [Hemolytic anemia due to cold-reacting antibodies: association with human immunodeficiency virus infection and non-Hodgkin's lymphoma]. AB - Hemolytic disease by cold-reacting antibodies is a rare form of hemolytic anemia. In most cases a subjacent cause is found. This disease is generally related with reactive lymphoproliferative processes (infections by the Epstein-Barr virus and cytomegalovirus) or uncontrolled lymphoproliferative disorders (lymphomas, Waldenstrom disease, chronic lymphatic leukemia). The presence of high titers of cryoagglutinins have recently been described in patients infected by the human immunodeficiency virus (HIV); however, clinical manifestation as hemolytic anemia is very rare. A 37 year old male diagnosed with infection by HIV, non Hodgkin's lymphoma of Burkitt type non convoluted cells, chronic hepatopathy by the B and C virus, Brouet type III cryoglobulinemia and hemolytic anemia by cold-reacting antibodies is herewith described. This multiple association is exceptional as is the important clinical repercussion of the hemolytic anemia derived from the high titers and above all the wide thermic interval of the cryoagglutinin present. Finally, the relation of cryoagglutinin with each of these entities, the concomitant presence of cryoglobulins and the evolution of the titers of the same with the chemotherapy treatment administered for the lymphoma is analyzed. PMID- 1583951 TI - [Febrile syndrome, splenomegaly and pancytopenia in a 23-year-old male with systemic lupus erythematosus]. PMID- 1583952 TI - [Xanthomonas maltophilia in a case of mixed infectious panniculitis]. PMID- 1583953 TI - [Oligoclonal bands in serum and cerebrospinal fluid in patients with suspected neuroborreliosis]. PMID- 1583954 TI - [Leiomyosarcoma of the foot]. PMID- 1583955 TI - [Non-cardiogenic pulmonary edema associated with boutonneuse fever]. PMID- 1583956 TI - [Cholestatic jaundice induced by captopril]. PMID- 1583957 TI - [Severe and recurrent infections in a patient with partial lipodystrophy and low C3 concentrations]. PMID- 1583958 TI - [Validation of a model of an automatic device for the ambulatory monitoring of blood pressure: the Spacelab 5200]. AB - BACKGROUND: The aim of this study was to test two of the same models of portable automatic devices for monitoring blood pressure over 24 hours. These devices were the Spacelabs 5200 (Kontron 1 and Kontron 2). METHODS: A mercury shygmomanometer was used as reference measurer. To validate Kontron 1, 22 persons (10 males and 12 females) of 45 +/- 12 years of age were selected. For Kontron 2, 25 subjects (12 males and 13 females) of 44 +/- 17 years of age were chosen. RESULTS: The results expressed as arithmetic mean and standard deviation were (manual vs Kontron 1); systolic blood pressure (SBP) 139 +/- 19 mmHg vs 135 +/- 16 mmHg, p less than 0.05; diastolic (DBP) 96 +/- 12 mmHg vs 93 +/- 12 mmHg, p less than 0.05, heart rate (HR) 77 +/- 13 ppm vs 76 +/- 14 ppm, NS. The correlation between the two methods was: SBP r = 0.870; DBP r = 0.875 and HR r = 0.949. The results of Kontron 2 were: SBP 137 +/- 17 mmHg vs 130 +/- 15 mmHg, p less than 0.05; DBP 93 +/- 11 mmHg vs 94 +/- 11 mmHg, NS; HR 75 +/- 10 ppm vs 73 +/- 12 ppm, NS. The correlations were: SBPr = 0.820; DBP r = 0.877 and HR r = 0.847. CONCLUSIONS: The Spacelabs 5200 automatic blood pressure monitoring underestimates systolic blood pressure while diastolic blood pressure and heart rate are reliable according to international norms. PMID- 1583959 TI - [Colorectal cancer: detection using the guaiac test at a primary care center]. AB - BACKGROUND: Colorectal cancer constitutes a serious health care problem in the Western world due to its frequency and mortality. Early detection and strict follow up of disease with risk of degeneration may increase survival. The guaiac test for fecal occult blood detection (one of the first signs of cancer) may contribute to the aforementiokned. METHODS: The guaiac test was randomly offered to patients consulting in general medicine. Those who accepted were taken to group meeting in general information and the test. Patients with positive tests underwent colonoscopy. Patients delaying the conclusion of the study were remained by telephone. Participation and the lesions detected were evaluated. RESULTS: The test was offered to 1,605 subjects, of whom 1,334 attended the meetings and 1,166 completed the test. Sixty patients were found to be positive and 52 underwent colonoscopy. The most significant diagnosis were 5 carcinomas at different stages and 25 neoplastic polyps. One hundred seventy-eight people were recouperated from 481 telephoned. CONCLUSIONS: The high participation in this study concerning early detection and follow up of disease with risk of degeneration to colorectal carcinoma is emphasized, in addition to the good response to the use of the telephone. Moreover, the low rejection to colonoscopy and the important lesions detected during this study are also of note. PMID- 1583960 TI - [Drug administration schedules in geriatric patients]. AB - BACKGROUND: In this study the prescription of drugs in an outpatients geriatric population was evaluated in terms of age and body weight. METHODS: From a wide survey carried out on 500 geriatric outpatients, all the prescriptions corresponding to H-2 antagonists, digoxin, theophylline, bromazepam, diazepam, lorazepam and triazolam were analyzed. The patients studied were of 60 or more years of age. For each drug patients were stratified into groups according to intervals of body weight with mean age of the patient being determined in each of the intervals as well as the doses received in mg/kg. RESULTS: Two hundred eighty prescriptions were analyzed with 12% corresponding to the H-2 antagonists, 29% to digoxin, 23% to theophylline and 35% to benzodiazepines. There was no significant correlation between age and the doses received. In general, the lowest body weight corresponded with a higher mean age and a marked increase in the mean dose of cimetidine, ranitidine, theophylline, bromazepam, lorazepam, and triazolam administered. There was a tendency to an adjustment in the doses of digoxin in the most elderly patients. CONCLUSIONS: The data found concerning the prescription of drugs to a geriatric outpatients population indicate that in elderly patients adjustments are not made in the doses of drugs administered according to the age and body weight of the patient. Low body weight of the elderly is a overdosage risk factor. PMID- 1583961 TI - ["Doctor, would you measure my blood pressure?"]. PMID- 1583962 TI - [Munchausen syndrome: another unpleasant problem]. PMID- 1583963 TI - [Acute pancreatitis associated with varicella-zoster virus infection in a patient with acquired immunodeficiency syndrome]. AB - A patient with the acquired immunodeficiency syndrome (AIDS) who developed acute pancreatitis (AP) during the course of a disseminated herpes zoster is presented. Diagnosis was based on the simultaneity of abdominal pain with hyperamylasemia, the dissemination of the cutaneous lesions and the positive varicella-zoster virus serology at titres 1/640. Response to acyclovir treatment was spectacular. To our knowledge this is the second case of AP produced by the varicella-zoster virus and the first described in the course of disseminated herpes zoster. We believe that the varicella-zoster virus should be included within the causes of AP in patients with the human immunodeficiency virus. PMID- 1583964 TI - [Association of sarcoidosis, diffuse centroblastic-centrocytic lymphoma and IgM monoclonal gammapathy in the same female patient]. AB - A case illustrating the infrequent association of sarcoidosis and lymphoma which was also a secretor of a monoclonal IgM paraprotein is described in a 68 year old woman. The first entity manifested by dyspnea corresponded with a bilateral interstitial pneumopathy with restrictive syndrome and was diagnosed by bronchoalveolar lavage and transbronchial biopsy and biopsy prescalenic fat. The lymphoma presented three years later followed by lymphadenopathies and a monoclonal IgM peak being diagnosed by biopsy of an axillary lymph node. In order to relate both entities it has been suggested that prolonged stimulation of the lymphocytes peculiar to the sarcoidosis would cause its malignant transformation. PMID- 1583965 TI - [Mediterranean boutonneuse fever of lethal course]. PMID- 1583966 TI - [The use of aminoglucosides in critical patients]. PMID- 1583967 TI - [Protocols and analysis of clinical decisions]. PMID- 1583968 TI - [Latex hypersensitivity]. PMID- 1583969 TI - [Primary tuberculosis of the esophagus]. PMID- 1583970 TI - [Hemoptysis and pulmonary infiltrates following crack poisoning]. PMID- 1583971 TI - [The effect of tobacco on glucose metabolism]. PMID- 1583972 TI - The political economy of scientific medicine: science, education and the transformation of medical practice in Sheffield, 1890-1922. PMID- 1583973 TI - William Stukeley and the gout. PMID- 1583974 TI - Buccaneering doctors. PMID- 1583975 TI - An example of meningiomatous hyperostosis from medieval Rochester. PMID- 1583976 TI - History of childbirth: fertility, pregnancy and birth in early modern Europe. Essay review. PMID- 1583977 TI - Shattered nerves: doctors, patients, and depression in Victorian England. Essay review. PMID- 1583978 TI - [Subcapsular hematoma of the liver in HELLP syndrome. An interdisciplinary emergency]. AB - The HELLP-syndrome (Hemolysis, Elevated Liver enzymes, Low Platelets), known as a complication during pregnancy, is associated with preeclampsia and may cause subcapsular liver hematomas. In case of hepatic rupture the lives of mother and unborn are threatened. Therefore, an interdisciplinary diagnostic and therapeutic approach is discussed and compared to two examples. The diagnosis of subcapsular liver hematoma must lead to urgent delivery through Cesarean section. Thereafter, the surgeon may decide between observation on an intensive care unit and urgent operation in case of hepatic rupture, without endangering the unborn. PMID- 1583979 TI - [Spieghel hernia--a rare cause of acute abdomen]. AB - Spieghelian hernia is a rare rupture of the abdominal wall along the linea semilunaris. Due to the fact that the rupture is overlain by the aponeurosis of M. externus abdominis, it is often not recognized in its early stage. In most cases the rupture neck is mostly very narrow and in 24.1% of all cases an incarceration of intestinal parts has ensued which may even lead to the development of an acute abdomen. The first choice therapy will consist in an operative support including the reposition of the hernial content and a possible resection of ischaemic organs as well as removal and sealing of the hernia. Because of the rarity of this sickness we report on a patient in our clinic who was operated as an emergency. PMID- 1583980 TI - [Surgical stapler technique for gastric tube formation and anastomosis after esophageal resection]. AB - 55 out of 62 patients being operated of esophageal carcinoma underwent gastric tube by stapling technique at the Department of General and Abdominal Surgery, Hospitals and Clinics, Johannes Gutenberg University, Mainz. In 32 cases the intrathoric anastomosis had been performed by using the circular stapling instrument. One patient (3.2%) out of two (6.3%) showing suture dehiscencies died consequently to this complication. A stenosis of the intrathoric anastomosis developed in 11 patients. The stapling technique convinced as a surgically simple and safe method of restructing the nutrition passage after esophageal resection. PMID- 1583981 TI - [Light and scanning electron microscopy study of the pathogenesis of pilonidal sinus and anal fistula]. AB - From various theories about the development of the pilonidal sinus Stelzner's opinion as to an acquired disease is generally accepted. Our scanning electron microscopic investigations strengthen this theory that hair splits and drills into the skin. Hooks keep it from retracting. Needlelike sharp ends may contribute to the hair piercing the skin. The anal fistula differs from the pilonidal sinus concerning morphology and pathogenesis. Surgical treatment must consider the localisation of the proctodeal gland. PMID- 1583982 TI - [What are the indications for surgical treatment of spinal fractures. Panel discussion]. PMID- 1583983 TI - [Alveolar echinococcosis: therapy with surgery, chemotherapy or a combination of the two?]. PMID- 1583984 TI - [Curative en-bloc resection (lung, diaphragm, liver, adrenal gland and thoracic wall) for echinococcus multilocularis. Report of an unusual disease course]. AB - Report concerning an en-bloc-resection of right lower lobe of the lung, diaphragm, right lobe of the liver, right adrenal gland, parts of the chestwall and a fistula for alveolar echinococcus. Combined postoperative treatment with mebendazol. More than 4 years postoperatively no evidence of a recurrency. PMID- 1583985 TI - [Scapulectomy as an extremity preserving intervention in surgery of soft tissue sarcoma]. AB - In the treatment of soft tissue sarcomas, radical surgery may mean total scapulectomy. If the tumour is localized next to the scapula wide margins can be better achieved by an operation of this kind than by resection of soft parts. In the planning of these operations radical surgery has priority. The functional results after total scapulectomy is acceptable. There is a distinct reduction of shoulder mobility, especially in abduction. As the peripheral joints are fully conserved, the extremity can be used very well in daily life. The indications for total scapulectomy and the technique are discussed with reference to two clinical cases. PMID- 1583986 TI - Morphological investigation of the porcine liver directly following preservation with Euro-Collins, University of Wisconsin and Bretschneider's HTK solution. AB - In order to study perfusion effects of different liver preservation methods on liver structure, porcine livers were perfused with either Bretschneider's HTK (Histidine Tryptophane Ketoglutarat) solution, Euro-Collins (EC) solution or University of Wisconsin solution (UW) according to the respective recommended protocols. Subsequently, together with a group of unprotected livers, all organs were examined by light and electron microscopy including computer assisted morphometry. The width of the space of Disse, the continuity of endothelial cells and the ultrastructure of the hepatocytes were not impaired after cold perfusion with any of the 3 solutions. However, we found considerable differences between the groups with respect to removal of blood cells from liver sinusoids. Livers flushed according to the HTK-protocol had the lowest residual blood cell content followed by the livers of the EC- and the UW-group. Centrilobular regions of the liver lobules were generally better washed free of blood than periportal zones. Computer assisted morphometry did not reveal any significant difference between the size of hepatocytes of EC-, UW- and HTK livers. Only the hepatocytes of normothermic control livers (biopsy samples) were 10% larger than hepatocytes of cold flushed groups. None of the protective perfusion protocols showed structural signs of perfusion injury. PMID- 1583987 TI - [Prognostic factors in diffuse peritonitis]. AB - In order to evaluate their prognostic relevance for survival 46 variables were submitted to univariate as well as multivariate analysis in a group of 184 patients with diffuse peritonitis. In the univariate analysis a significant correlation with the outcome was found for the following parameters: age greater than or equal to 70 years, preexisting hepatic or cardiac disease, no eradication of the primary source of infection at first laparotomy for peritonitis, cardiovascular instability, respiratory failure, hyperbilirubinemia, thrombocytopenia, elevated serum creatinine and diminished creatinine clearance at the beginning and proof of pseudomonas aeruginosa in the peritoneal exsudate and of candida albicans in the blood culture during the course of the peritonitis. In the multivariate analysis the surgical eradication of the primary source of infection at the first laparotomy for peritonitis, serum creatinine at the beginning of peritonitis, age greater than or equal to 70 years and a preexisting hepatic disease proved to be the independent variables with significant prognostic relevance for survival of the patients. PMID- 1583988 TI - [Surgery of rectal cancer--today]. PMID- 1583989 TI - [Diagnosis and therapeutic possibilities of descending perineum syndrome]. AB - The Descending-Perineum-Syndrome (DPS) is a quite common disease in the coloproctological outpatient clinic. In some cases it is difficult to get the correct diagnosis. The treatment success is depending on the condition of the muscle of the floor of the pelvis and on the condition of the sphincter internus- and externus muscle and on the various operation methods. One of these operation methods is the rectopexy with suspension of the anterior wall of the rectum and in some cases in combination with a colon-resection. After this kind of operation 75% of these patients had no pain and less defecation problems. PMID- 1583990 TI - [Rectal cancer--results of continence-preserving resections]. AB - In a series of 586 patients with rectal carcinoma who underwent potentially curative resection between January 1977 and December 1990 postoperative complications, incidence of local recurrence and disease free survival are investigated. Of the 401 patients undergoing low anterior resection (LAR) and 89 patients with coloanal anastomosis (CAA) 389 anastomoses were fashioned with staples. The hospital mortality rate was 4.6%. Clinical anastomotic leakage occurred in 5.5% (handsewn 10.3% stapled 4.3% (p less than 0.05), anastomotic strictures in 7.5% and 2.4% (p less than 0.05). 20% of patients undergoing restaurative resection (RR) (handsewn 23%, stapled 20%) developed local recurrences compared with 21% for the group with abdominoperineal resection (APR). The corrected 5-year survival rate was 63% for RR respectively 55% for APR (p greater than 0.05). After CAA, incidence of local recurrence and survival rate for patients with carcinoma of the lower rectum was 11% respectively 63%. It is concluded that innovative advances like the development of circular stapling devices and the adoption of a more aggressive sphincter-saving policy like CAA cause not an increased risk of recurrent diseases and no decrease of the 5-year survival rate. PMID- 1583991 TI - [Functional disorders after deep rectum resection: is pouch formation recommended?]. AB - After low colo-rectal or colo-anal anastomosis there is in 25% a degree of urgency and increased bowel movements. In order to improve the reservoir continence the construction of a J-shaped colonic pouch seems reasonable. We have operated 5 patients with the new technique and worked up our preliminary results in connection with a literature overview. Increased bowel movements and urgency are reduced postoperatively but some patients report pouch evacuation problems, using enemas or suppositories to empty their reservoirs. To estimate the value of this new technique innovative endpoints as overall well-being and quality of life might be more important than conventional endpoints measuring only functional results. PMID- 1583992 TI - [The plotting of intraventricular pressure-volume diagrams using intracardiac impedance volumetry]. AB - The theoretical and practical aspects of a method for continuous measurements of the left ventricular volume are reviewed. The method is based on high frequency intracardiac impedance measurements. The mathematic model, results of computer simulation are given as are equations for calculating the volume of the left ventricle of the heart. A computer program for measurements automation and the plotting of intraventricular pressure-volume diagrams is described. PMID- 1583993 TI - [Improvement of the parameters of luminous lighting, diagnostic and therapeutic light devices]. AB - The paper is concerned with certain potentialities of enhancing the intensity of illumination of luminous devices fitted out with light guides used for shadowless illumination, diagnosis and thermal polymerization of filling photocompositions. Optimization of the geometry of the light concentrator is regarded as the main factor of enhancing the intensity of illuminations. Recommendations are given for the use of metallo-halogenic lamps for the same purposes. PMID- 1583994 TI - [A system of automatic increase control of pulse oxyhemometer channels]. PMID- 1583995 TI - [Choice of parameters of primary transformers of body surface fluctuations]. AB - The authors review distortions of body surface fluctuations provoked by the action of primary transformers (PT). It is suggested that conditions of PT contact with the body surface may be standardized. As far as transformers measuring the kinematic parameter of fluctuations are concerned, those existing in the absence of any action on the surface should be regarded as undistorted. As for PTs that transform the power parameter, the conditions for undistorted reception involve complete inhibition of the surface under study. It is proposed that the degree of distortions may be estimated in the form of the "measurement method error". It is shown that error of the method can be restricted at the present level, if the design parameters of PT that determine the conditions of contact are chosen in terms of the correlations provided in the paper. PMID- 1583996 TI - [Hydrodynamic criteria in the choice of surgical tactics in implanting pulmonary artery trunk prosthesis]. AB - The paper is concerned with the present-day problem of modern medicine, namely with surgical correction of the diseases of the initial part of the pulmonary circulation. The authors suggest hemohydrodynamic simulation of the right heart complicated by extracardial conduit. The simulation was performed at the high theoretical, practical and methodological level to obtain highly significant information which is likely to have paramount importance for clinical practice. PMID- 1583997 TI - [Principles of the design of the equipment for intermittent normobaric hypoxia]. AB - The author relates the principles of the design of the equipment for intermittent normobaric hypoxia. Provides the classification of diagrams, notes advantages and short-comings of the hypoxicators of both groups (forming gas hypoxic mixtures from compressed gases and atmospheric air). Delineates areas where they can be used efficiently. PMID- 1583998 TI - [A vocal processor for cochlear prosthesis]. AB - The authors review problems of the design of an experimental sample of a laboratory vocal processor for cochlear implantation. Provide a brief description of the work modes and potentialities of the device. Present the tentative data on electric stimulation of the cochlea. Conclude that the device can be used both in research and practical work in the area of cochlear implantation. PMID- 1583999 TI - [Thermal characteristics of the thermostat 2TG-0-05 for plates]. AB - The paper is concerned with the results of thermotechnical testing of the Soviet thermostat 2T gamma-0-05 for plates. The thermostat employs dry air, preheating, circulation. As to the productivity, accuracy of the preset temperature maintenance, uniformity of the field of temperatures in the working area of the chamber, intensity of heat exchange of the air flow with the samples in plate cells, the 2T gamma-0-05 thermostat compares very favourably with foreign analogs. In addition to its main use, the thermostat can be applied to thermostatic control of test tubes containing biosamples or chemical reagents. The thermostat chamber is intended for placing in it of a device for shaking AB 10II plates or an apparatus for shaking AB-30C test tubes. PMID- 1584000 TI - [A device for the control of energy characteristics of ultraviolet irradiators of blood]. PMID- 1584001 TI - [A portable device for checking equipment and programs of detecting flutter and fibrillation of heart ventricles in humans]. AB - Facilities and programs of detecting ventricular flutter and ventricular fibrillation of the heart of man are important units of cardiomonitors. The life of cardiological patients staying at the departments for intensive care depend in many respects on the quality of the units in question. Using a portable simulator of three types of ventricular fibrillation and ventricular flutter it is possible to check up the service-ability and safety of the given units. The main parameters of the simulator are chosen on the basis of the statistical and spectral characteristics of real ventricular fibrillation and ventricular flutter, derived by the authors as a result of the experimental studies. Those characteristics can also be used for optimizing facilities and programs of detecting ventricular fibrillation and ventricular flutter. PMID- 1584002 TI - [Eddy current locator of foreign bodies]. PMID- 1584003 TI - [Equipment for extracorporeal handling of physiological fluids]. PMID- 1584004 TI - Brucella abortus deficient in copper/zinc superoxide dismutase is virulent in BALB/c mice. AB - The gene encoding the Cu/Zn superoxide dismutase (SOD) of Brucella abortus strain 2308 was identified in a Brucella genomic library utilizing a combination of Western blotting and native gel electrophoresis. The Cu/Zn SOD gene was inactivated in vitro by ligation of a kanamycin resistance gene into the open reading frame encoding SOD. The plasmid born construct was introduced back into B. abortus by electroporation. Replacement of the wild-type Cu/Zn SOD by recombination was demonstrated by showing that both the KnR gene and the Cu/Zn SOD gene hybridized to the same band in a Southern analysis of genomic DNA. In addition, KnR strains were deficient in Cu/Zn SOD activity as assessed by lack of Cu/Zn SOD activity on a native gel and by lack of reactivity with specific serum in a Western analysis. Either strain 2308 or the Cu/Zn SOD deficient mutant injected intraperitoneally into BALB/c mice, exhibited no differences in their ability to colonize the spleen at 7 and 28 days post-inoculation. Thus, the inability to produce Cu/Zn SOD by B. abortus does not significantly impair its virulence in mice. PMID- 1584005 TI - Effect of Legionella pneumophila cytotoxic protease on human neutrophil and monocyte function. AB - The extracellular metalloprotease of Legionella pneumophila, also called tissue destructive protease or major secretory protein, has been proposed as one of the virulence factors of this organism. Considering the decisive role played by the phagocytic cells in host defense against Legionella infection, we investigated the effect of this protease on the function of human neutrophils and monocytes. L. pneumophila protease inhibited the chemotactic response of neutrophils to F Met-Leu-Phe and zymosan-activated serum in a concentration-dependent and heat labile manner. A direct effect of the protease on the chemotactic activity of neutrophils was demonstrated by the continued inhibition of neutrophil chemotaxis when the protease was removed following pre-incubation of the cells. In contrast, the enzyme had no effect on monocyte chemotaxis. The protease inhibited, also in a concentration-dependent and heat-labile manner, the binding of F-Met-Leu-Phe to both cell types. Neutrophil and monocyte oxidative burst response, as measured by superoxide release and chemiluminescence response, was not significantly affected by the enzyme. A slight enhancement of PMA-stimulated superoxide release was induced by the protease in both cell types. Lastly, the protease inhibited the killing of Listeria monocytogenes by neutrophils or monocytes. Inhibition of Listeria killing was concentration-dependent, heat-labile, and did not require the presence of the enzyme in the bactericidal assay. The inhibitory activity of L. pneumophila protease on neutrophil chemotaxis and on the listericidal activity of human neutrophils and monocytes demonstrated in this study provides evidence for a role of this enzyme in the pathogenesis of Legionnaires' disease. PMID- 1584006 TI - Evaluation of Salmonella typhimurium strains harbouring defined mutations in htrA and aroA in the murine salmonellosis model. AB - Derivatives of the mouse-virulent Salmonella typhimurium strain SL1344 were constructed harbouring defined mutations in htrA, aroA or htrA aroA combined. When administered orally or intravenously to BALB/c mice, all the mutants were found to be highly attenuated. All mutants were able to confer significant protection against lethal challenge with SL1344 after a single oral dose of live organisms. SL1344 htrA mutants persisted in livers and spleens at a lower level than SL1344 aroA mutants after intravenous administration. SL1344 htrA aroA mutants persisted at an even lower level and were cleared from the livers and spleens of mice within 21 days of intravenous administration. Thus htrA and htrA aroA mutants can be considered as potential oral vaccines against salmonellosis. PMID- 1584007 TI - In vitro adherence property of cytolethal distending toxin (CLDT) producing EPEC strains and effect of the toxin on rabbit intestine. AB - Sixteen cytolethal distending toxin-producing enteropathogenic Escherichia coli (CLDT+ EPEC) strains of six different serogroups were included in this study. The strains showed varying adherence patterns on HEp-2 cells, i.e. six strains showed localized adherence (LA), five strains exhibited diffuse adherence (DA) and five strains were non-adherent. Histological study of rabbit ileal segments showed that live cultures of CLDT+ EPEC did not cause lesions characteristic of attachment and effacement (AE) and the toxin effect resembled that of classical LT or CT. PMID- 1584008 TI - Quantitative assessment of the ability of Escherichia coli to invade cultured animal cells. AB - Assays to quantify bacterial invasion of epithelial cells generally fail to take account of the ability of the bacteria to adhere to the cells prior to invasion. We have developed a modified invasion assay to allow for this factor. We then used the assay to investigate diarrhoeagenic strains of Escherichia coli with differing ability to adhere to and invade HEp-2 epithelial cells. The results showed that enteroinvasive strains of E. coli were the most invasive variety, followed in order by enteropathogenic E. coli and enterotoxigenic E. coli. These findings correspond to what is known of the ability of the bacteria to invade the intestinal tract in vivo. The results also indicated that adhesins of diarrhoeagenic E. coli play no direct role in invasion, although they may facilitate invasion indirectly by promoting initial contact between bacteria and animal cells. PMID- 1584009 TI - Positive selection and interallelic recombination at the merozoite surface antigen-1 (MSA-1) locus of Plasmodium falciparum. AB - DNA sequences of alleles at the merozoite surface antigen-1 (MSA-1) gene locus of the malaria parasite Plasmodium falciparum show evidence of repeated past recombination events between alleles. These include both (1) nonreciprocal recombination events that have homogenized certain gene regions among alleles and (2) reciprocal recombination events that have combined allelic segments with divergent evolutionary histories, thereby enhancing allelic diversity. In three different gene regions, the rate of nonsynonymous nucleotide substitution significantly exceeds that of synonymous nucleotide substitution, implying that positive Darwinian selection has acted to diversify alleles at the amino acid level. The MSA-1 polymorphism seems to be quite ancient; the two major allelic types have been maintained for approximately 35 Myr. PMID- 1584010 TI - Selection of laboratory wild-type phenotype from natural isolates of Escherichia coli in chemostats. AB - We have followed, in glucose-limited chemostats, the evolution of natural isolates of Escherichia coli possessing maximal growth rates of 0.48-1.43 doublings/h. Under these conditions a rapid-growth phenotype similar to that of standard laboratory wild-type strains was selected so that after 280 generations all of the cultures were characterized by bacteria with maximum growth rates close to 1.33 doublings/h. The growth yields of the natural isolates, on the other hand, were quite uniform and improved only slightly during the selection; it seems that the natural isolates are nearly maximally efficient at utilizing glucose. Some of the kinetic characteristics of ribosomes prepared from natural isolates vary markedly and in proportion to the growth rates of the original strains. After growth in glucose-limited chemostats, the ribosomes of all of the cultures become kinetically indistinguishable from those of laboratory wild-type bacteria. These observations confirm the interpretation that bacteria grown under normal laboratory conditions have been selected for maximum growth rates which demand maximum translation efficiency. In contrast, these characteristics do not seem to be strongly selected in the natural isolates. PMID- 1584011 TI - Major-histocompatibility-complex DRB genes of a New-World monkey, the cottontop tamarin (Saguinus oedipus). AB - The DRB region of the human and great-ape major histocompatibility complex displays not only gene but also haplotype polymorphism. The number of genes in the human DRB region can vary from one to four, and even greater variability exists among the DRB haplotypes of chimpanzees, gorillas, and orangutans. Accumulating evidence indicates that, like gene polymorphism, part of the haplotype polymorphism predates speciation. In an effort to determine when the gene haplotype polymorphisms emerged in the primate lineage, we sequenced three cDNA clones of the New-World monkey, the cottontop tamarin (Saguinus oedipus). We could identify two DRB loci in this species, one (Saoe-DRB1) occupied by apparently functional alleles (*0101 and *0102) which differ by only two nucleotide substitutions and the other (Saoe-DRB2) occupied by an apparent pseudogene. The Saoe-DRB2 gene contains an extra sequence derived from the 3' portion of exon 2 and placed 5' to this exon. This sequence contains a stop codon which makes the translation of the bulk of the Saoe-DRB2 gene unlikely. Preliminary Southern blot hybridization analysis with probes derived from these two genes suggests that both the DRB gene polymorphism and the haplotype polymorphism in the cottontop tamarin may be low. In most individuals the DRB region of this species probably consists of three genes. Comparisons of the Saoe DRB sequences with those of other primates suggest that probably all of the DRB genes found until now in the Catarrhini were derived from a common ancestor after the separation of the Catarrhini and Platyrrhini lineages. The extant DRB gene and haplotype polymorphism may therefore have been founded in the mid-Oligocene some 33 Mya. PMID- 1584012 TI - The involucrin gene of Old-World monkeys and other higher primates: synapomorphies and parallelisms resulting from the same gene-altering mechanism. AB - The involucrin gene of platyrrhines and hominoids contains a segment of 10-codon repeats which were added vectorially at the same site in the coding region. We have now cloned and sequenced the involucrin gene of four cercopithecoid monkeys- two macaques (mulatta and fascicularis) and two Cercopithecus monkeys (aethiops and hamlyni). Each gene contains a similar segment of short repeats; some of these were added in a common anthropoid lineage, others were added in a common catarrhine lineage, and still others were added in a common macaque or Cercopithecus lineage. Repeats added before a lineage diverges become synapomorphies in the sister taxa resulting from the divergence. Repeats added independently in different diverged lineages become parallelisms. The synapomorphies are the result of the action of a targeted duplication mechanism acting in a common ancestral lineage, but the parallelisms are the result of the same duplication mechanism transmitted to successively divergent sublineages and acting independently in each. PMID- 1584013 TI - Phylogeny of the Bovidae (Artiodactyla, Mammalia), based on mitochondrial ribosomal DNA sequences. AB - Portions of the 12S and 16S mitochondrial ribosomal genes for 16 species representing nine tribes in the mammal family Bovidae were compared with six previously published orthologous sequences. Phylogenetic analysis of variable nucleotide positions under different constraints and weighting schemes revealed no robust groupings among tribes. Consensus trees support previous hypotheses of monophyly for four clades, including the traditional subfamily Bovinae. However, the basal diversification of bovid tribes, which was largely unresolved by morphological, immunodiffusion, allozyme, and protein sequence data, remains unresolved with the addition of DNA sequence data. The intractability of this systematic problem is consistent with a rapid radiation of the major bovid groups. Several analyses of our data show that monophyly of the Bovidae, which was weakly supported by previous morphological and molecular work, is questionable. PMID- 1584014 TI - Mitochondrial DNA evolution at a turtle's pace: evidence for low genetic variability and reduced microevolutionary rate in the Testudines. AB - Evidence is compiled suggesting a slowdown in mean microevolutionary rate for turtle mitochondrial DNA (mtDNA). Within each of six species or species complexes of Testudines, representing six genera and three taxonomic families, sequence divergence estimates derived from restriction assays are consistently lower than expectations based on either (a) the dates of particular geographic barriers with which significant mtDNA genetic clades appear associated or (b) the magnitudes of sequence divergence between mtDNA clades in nonturtle species that otherwise exhibit striking phylogeographic concordance with the genetic partitions in turtles. Magnitudes of the inferred rate slowdowns average eightfold relative to the "conventional" mtDNA clock calibration of 2%/Myr sequence divergence between higher animal lineages. Reasons for the postulated deceleration remain unknown, but two intriguing correlates are (a) the exceptionally long generation length most turtles and (b) turtles' low metabolic rate. Both factors have been suspected of influencing evolutionary rates in the DNA sequences of some other vertebrate groups. Uncertainities about the dates of cladogenetic events in these Testudines leave room for alternatives to the slowdown interpretation, but consistency in the direction of the inferred pattern, across several turtle species and evolutionary settings, suggests the need for caution in acceptance of a universal mtDNA-clock calibration for higher animals. PMID- 1584015 TI - Comparative structural analysis of the transcriptionally active proopiomelanocortin genes A and B of Xenopus laevis. AB - In the intermediate lobe of the pituitary gland, the prohormone proopiomelanocortin (POMC) is processed to, among other peptides, melanocyte stimulating hormone (alpha-MSH). In the toad Xenopus laevis alpha-MSH controls skin darkening during background adaptation, and the level of POMC gene transcription in the intermediate lobe depends on the color of the background. In the lobe, two structurally different POMC proteins are produced from two mRNAs that are transcribed to approximately the same level from two POMC genes (A and B). We previously reported the entire nucleotide sequence of Xenopus POMC gene B. To identify conserved-- and thus potential regulatory--DNA elements in the Xenopus POMC gene, we here report the determination and analysis of the complete nucleotide sequence of Xenopus POMC gene A and its 5'- and 3'-flanking regions. Comparison of the two Xenopus POMC genes revealed, in addition to the exons, three highly conserved regions. First, the promoter regions are greater than 90% identical. The second region concerns JH12 repetitive elements situated at approximately the same position in both genes. These elements are greater than 86% identical. The third region is a 500-bp sequence just upstream of exon three (63% identity). Besides these three large regions, several small regions with significant identity were found at similar positions in the two POMC genes. The fact that, except for the JH12 element, the repetitive elements are not conserved between the two POMC genes indicates that these repeats are not functionally important. PMID- 1584016 TI - Nucleotide sequence of nifD from Frankia alni strain ArI3: phylogenetic inferences. AB - The complete nucleotide sequence of the nifD gene encoding the alpha subunit of component I of nitrogenase from Frankia alni strain ArI3 was determined. The coding region is 1,458 bp in length and encodes a polypeptide of 486 residues with a predicted molecular weight of 53,500. Phylogenetic inferences with 12 complete published nifD sequences were drawn using a variety of approaches. Frankia nifD clusters with proteobacteria rather than with Clostridium pasteurianum, the other Gram-positive bacterium studied. Extant eubacterial nif genes seem to have at least three distinct evolutionary origins as a result of ancient gene duplications. Within the Gram-positive bacterial phylum, functional nif genes descend from different duplicates. PMID- 1584017 TI - A comprehensive study of genic variation in natural populations of Drosophila melanogaster. VII. Varying rates of genic divergence as revealed by two dimensional electrophoresis. AB - Four sibling species from the melanogaster subgroup (Drosophila melanogaster, D. simulans, D. sechellia, and D. mauritiana) were studied for genetic divergence, by high-resolution two-dimensional protein electrophoresis (2DE) coupled with ultrasensitive silver staining. A total of eight tissues from larval and adult developmental stages representing both gonadal (germ-line) and nongonadal (somatic) tissues were analyzed for protein divergence between species. Close to 400 polypeptides (protein spots) were scored from each tissue and species, and protein divergence was measured on the basis of qualitative differences (presence/absence) of protein spots in pairwise species comparisons. The observed levels of genic divergence varied among tissues and among species. When larval hemolymph proteins (which are known to be highly polymorphic) were excluded, there was no evidence to suggest that either the larval or adult-stage proteins, as a whole, are more diverged than the other; variation between different tissues rather than between developmental stages appears to be the most significant factor affecting genetic divergence between species. The reproductive tissue (testis and accessory gland) showed more divergence than did the nonreproductive tissue; D. melanogaster testis (from both larvae and adult males) showed the highest level of divergence. In view of the previous observation that D. simulans, D. mauritiana, and D. sechellia show similar but significantly less reproductive isolation from each other than from D. melanogaster, the present results suggest a correlation between the levels of reproductive-tract-protein divergence and the degree of reproductive isolation in these species. PMID- 1584018 TI - An association between ADH protein levels and polymorphic nucleotide variation in the Adh gene of Drosophila melanogaster. AB - Southern analysis of the Adh region of 212 Drosophila melanogaster lines collected from the Tahbilk winery revealed linkage disequilibrium between a 37-bp insertion [designated delta 2 by Kreitman (1983)] and the fast electrophoretic variant of alcohol dehydrogenase (ADH-F). Among these lines 34% contained the insert and encoded ADH-F, 33.5% encoded ADH-F and did not have the insert, and 32.5% encoded the slow electrophoretic variant of alcohol dehydrogenase (ADH-S). Strong linkage association between this insert and ADH-F is evident worldwide. Twenty-nine of the second chromosome lines were characterized for ADH protein quantity by using radial immunodiffusion. ADH quantity was estimated in both larvae and adult males raised in the presence and absence of alcohol supplement to each of two different food media. Analyses of variance indicated higher levels of ADH protein in larvae from lines with the insert (all ADH-F), compared with those without (both ADH-F and ADH-S), independent of either dietary alcohol or media type. No such difference in ADH quantity between insert- and noninsert containing ADH-F lines was detected in adults, although the expected higher levels occurred in ADH-F lines compared with ADH-S lines. Given the high levels of linkage disequilibrium in the Adh region, these data suggest that either polymorphic nucleotide-site variants positively associated with delta 2 on the second chromosome or delta 2 itself increases larval levels of ADH protein. PMID- 1584019 TI - The consistency of several phylogeny-inference methods under varying evolutionary rates. AB - A phylogenetic method is a consistent estimator of phylogeny if and only if it is guaranteed to give the correct tree, given that sufficient (possibly infinite) independent data are examined. The following methods are examined for consistency: UPGMA (unweighted pair-group method, averages), NJ (neighbor joining), MF (modified Farris), and P (parsimony). A two-parameter model of nucleotide sequence substitution is used, and the expected distribution of character states is calculated. Without perfect correction for superimposed substitutions, all four methods may be inconsistent if there is but one branch evolving at a faster rate than the other branches. Partial correction of observed distances improves the robustness of the NJ method to rate variation, and perfect correction makes the NJ method a consistent estimator for all combinations of rates that were examined. The sensitivity of all the methods to unequal rates varies over a wide range, so relative-rate tests are unlikely to be a reliable guide for accepting or rejecting phylogenies based on parsimony analysis. PMID- 1584020 TI - Escherichia coli HlyT protein, a transcriptional activator of haemolysin synthesis and secretion, is encoded by the rfaH (sfrB) locus required for expression of sex factor and lipopolysaccharide genes. AB - Synthesis and secretion of the 110kDa haemolysin toxin of Escherichia coli and other pathogenic Gram-negative bacteria are governed by the four genes of the hly operon. We have identified, by transposon mutagenesis, an E. coli cellular locus, hlyT, required for the synthesis and secretion of haemolysin encoded in trans by intact hly operons carrying the hly upstream regulatory region. Mutation of the hlyT locus specifically reduced the level of hlyA structural gene transcript 20 100-fold and thus markedly lowered both intracellular and extracellular levels of the HlyA protein. Genetic and structural analysis of the hlyT locus mapped it at co-ordinate 3680 kbp (minute 87) on the chromosome adjacent to the fadBA operon, and identified it specifically as the rfaH (sfrB) locus which is required for transcription of the genes encoding synthesis of the sex pilus and also the lipopolysaccharide core for attachment of the O-antigen of E. coli and Salmonella. Expression of the hly operon in the E. coli hlyT mutant was restored in trans by both the hlyT and rfaH genes, suggesting that the rfaH gene is an important activator of regulon structures that are central to the fertility and virulence of these pathogenic bacteria. DNA sequencing of the hlyT locus identifies the HlyT/RfaH transcriptional activator as a protein of 162 amino acids (Mr 18325) which shows no identity to characterized transcription factors. PMID- 1584021 TI - A bifunctional xylanase encoded by the xynA gene of the rumen cellulolytic bacterium Ruminococcus flavefaciens 17 comprises two dissimilar domains linked by an asparagine/glutamine-rich sequence. AB - The nucleotide sequence of the xynA gene of Ruminococcus flavefaciens 17 was determined and found to consist of a 2862bp open reading frame beginning with a TTG start codon. The predicted product, XYLA, consisted of distinct amino terminal (A) and carboxy terminal (C) domains (248 amino acids, including a putative signal sequence, and 332 amino acids, respectively) linked by a repetitive sequence (B, 374 amino acids) extraordinarily rich in asparagine (45%) and glutamine (26%) residues. Domains A and C were shown to be capable of expressing xylanase activity independently of each other when suitably truncated derivatives of the xynA coding region were expressed as lacZ fusions. The activities associated with the two domains were shown to differ with respect to the average size of hydrolysis products formed from oat-spelt xylan, with domain C releasing relatively more xylose and domain A more xylo-oligosaccharides. The amino acid sequence of domain A of XYLA closely resembled that of the Bacillus pumilus xynA enzyme (45% identical residues). On the other hand domain C showed significant similarity (33% to 40% identical residues) to a different group of bacterial xylanases and exoglucanases exemplified by the Caldocellum saccharolyticum xynA and celB products. The xynA product is, therefore, a bifunctional enzyme having two dissimilar catalytic domains capable of acting on xylan. PMID- 1584022 TI - Elongation factor 3 (EF-3) from Candida albicans shows both structural and functional similarity to EF-3 from Saccharomyces cerevisiae. AB - As with many other fungi, including the budding yeast Saccharomyces cerevisiae, the dimorphic fungus Candida albicans encodes the novel translation factor, elongation factor 3 (EF-3). Using a rapid affinity chromatography protocol, EF-3 was purified to homogeneity from C. albicans and shown to have an apparent molecular mass of 128 kDa. A polyclonal antibody raised against C. albicans EF-3 also showed cross-reactivity with EF-3 from S. cerevisiae. Similarly, the S. cerevisiae TEF3 gene (encoding EF-3) showed cross-hybridization with genomic DNA from C. albicans in Southern hybridization analysis, demonstrating the existence of a single gene closely related to TEF3 in the C. albicans genome. This gene was cloned by using a 0.7 kb polymerase chain reaction-amplified DNA fragment to screen to C. albicans gene library. DNA sequence analysis of 200 bp of the cloned fragment demonstrated an open reading frame showing 51% predicted amino acid identity between the putative C. albicans EF-3 gene and its S. cerevisiae counterpart over the encoded 65-amino-acid stretch. That the cloned C. albicans sequence did indeed encode EF-3 was confirmed by demonstrating its ability to rescue an otherwise non-viable S. cerevisiae tef3:HIS3 null mutant. Thus EF-3 from C. albicans shows both structural and functional similarity to EF-3 from S. cerevisiae. PMID- 1584023 TI - Mobilization protein-DNA binding and divergent transcription at the transfer origin of the Thiobacillus ferrooxidans pTF1 plasmid. AB - The possible interaction of the trans-acting mobilization proteins, MobL and MobS, at the cognate origin of transfer (oriT) region of the Thiobacillus ferrooxidans plasmid pTF1 has been investigated. In gel retardation assays with crude protein extracts from overproducing strains, a truncated MobL (c. 28 kDa) as well as its native protein (42 kDa), but not the 11 kDa MobS protein, were found to bind specifically to a 42-mer oligonucleotide which represents the transferred DNA strand of the minimal oriT fragment of pTF1. In vivo, the binding of MobL was studied by monitoring catechol 2,3-dioxygenase (xylE) activities driven by promoters of the divergently transcribed mobL and mobS genes. The mob promoter sequences were found to resemble the Escherichia coli sigma 70-dependent consensus promoter elements. The '-10' recognition sequences of mobL and one of the two mobS promoters overlap except for one base and they are positioned within the putative 'hairpin' structure in the minimal oriT sequence. In accordance with the twin supercoil-domain model of Liu and Wang (1987) which suggests that transcription can generate local variations in DNA superhelicity, we propose a possible physiological role of DNA supercoiling in the transfer origin with reference to divergent transcription of mobL and mobS genes. PMID- 1584024 TI - The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. PMID- 1584025 TI - Effect of lac repressor oligomerization on regulatory outcome. AB - Regulatory outcome in a bacterial operon depends on the interactions of all the components which influence mRNA production. Levels of mRNA can be altered profoundly by both negative and positive regulatory elements which modulate initiation of transcription. The occupancy of regulatory sites on the DNA by repressors and activators is determined not only by the affinity of these proteins for their cognate site(s) but also by the oligomeric state of the regulatory protein. The lac operon in Escherichia coli provides an excellent prototypic example of the influence of protein assembly on the transcriptional status of the associated structural genes. DNA loop formation is essential for maximal repression of the lac operon and is contingent upon the presence of multiple operator sites in the DNA and the ability of the repressor to self associate to form a bidentate tetramer. The stability of this looped complex is enhanced significantly by DNA supercoiling. Tetramer assembly from dimers apparently occurs via interactions of a 'leucine zipper' motif in the C-terminal domain of the protein, and the tetramer is essential to formation of looped complexes. Furthermore, analysis of the DNA-binding characteristics of dimeric mutants has established that the monomer-dimer association and dimer-DNA binding (monomer does not bind to DNA) are coupled equilibria. Thus, dimer assembly is essential for generating a DNA-binding unit, and tetramer assembly is required for formation of the stable looped DNA structure that maximally represses mRNA synthesis. Protein-protein interactions therefore play a pivotal role in the regulatory activities of the lac repressor and must be considered when analysing the activities of any oligomeric DNA-binding protein. PMID- 1584027 TI - Cloning and sequence of a beta-tubulin cDNA from Pneumocystis carinii: possible implications for drug therapy. AB - This work describes the isolation and characterization of a full-length cDNA clone encoding beta-tubulin from the pathogen Pneumocystis carinii. P. carinii contains a single gene encoding beta-tubulin. The complete sequence of this cDNA has been determined and its inferred amino acid sequence compared with the beta tubulins from other organisms. This analysis augments the data indicating that P. carinii should be classified as a fungal organism. Further comparisons between the P. carinii beta-tubulin and those of fungal beta-tubulins resistant to benomyl, a beta-tubulin-binding drug, indicate a difference which may be exploited in the development of a new drug therapy for P. carinii pneumonitis. These results suggest that, theoretically, a drug presently administered for treatment of nematode worm infections may be an effective agent against P. carinii, without being toxic to the mammalian host. This possibility is currently being investigated. PMID- 1584026 TI - Global changes in gene expression related to antibiotic synthesis in Streptomyces hygroscopicus. AB - Two-dimensional gel electrophoresis was used to follow changes in gene expression associated with antibiotic (bialaphos) biosynthesis in Streptomyces hygroscopicus. Cultures were pulse-labelled with [35S]-methionine before, during, and after the switch from primary to secondary metabolism in order to compare kinetic profiles of bialaphos (antibiotic) production (bap) genes during this metabolic transition. Separation of gene products on two-dimensional gels revealed that 27 were dependent on brpA for optimal expression and were activated as the culture approached stationary phase. Genes which encoded 10 brpA-dependent proteins were mapped to a 10 kb SstI fragment of the 35 kb bap gene cluster by expressing them in Streptomyces lividans using the thiostrepton-inducible tipA promoter. N-terminal amino acid sequences of two brpA-dependent proteins, obtained by direct microsequencing of protein spots excised from two-dimensional gels, identified them as gene products mapping to the same region and involved in secondary metabolic conversions of the bap pathway. The kinetics of synthesis of 16 brpA-dependent gene products were characterized using QUEST computer software. Cluster analysis performed on the kinetics of synthesis of 346 of the most highly expressed gene products of HP5-29, including 16 brpA-dependent ones, identified 75 families having distinct patterns of expression. Many brpA-dependent proteins were clustered together; 10 were found in one kinetic family. These kinetic families also included brpA-independent gene products perhaps subject to similar regulatory mechanisms and thus possibly involved in bialaphos biosynthesis. The activation/derepression of bap expression took place as cultures approached stationary phase and was temporally related to synthesis of ppGpp. PMID- 1584028 TI - A family affair. PMID- 1584029 TI - Placement practices in specialized foster homes and small group homes for persons with mental retardation. AB - Resident functional and personal characteristics (e.g., gender, race, age, and level of mental retardation), placement histories, and projected placements of a nationally representative sample of 336 persons with mental retardation living in a total of 181 small, specialized foster care homes and group homes with 6 or fewer residents were compared. In addition, the extent to which resident characteristics differentiate between persons placed in specialized foster care homes or small group homes was assessed. Results indicate that there are some differences in resident characteristics across facility type, including communication and toileting skills, age, and mobility. Overall, results showed that small foster and group homes successfully serve a variety of people and that placement generally lasts for several years. PMID- 1584030 TI - An eight-year follow-up of three social skills training studies. AB - An 8-year follow-up of the maintenance of social skills training effects was conducted. Nine subjects from previously published studies that targeted general/social, social/vocational, and social/sexual skills were retested in role play or interview/simulation generalization assessments. The follow-up tests revealed that 5 subjects' correct responding was maintained well above their pretrained or baseline levels, and 3 responded above their posttest levels. Increases in an untargeted response, number of words per response, were maintained for most of the subjects whose percentage correct responding was maintained. The results suggest that some individuals will display enduring situation-specific social responding. PMID- 1584031 TI - Recurrence of neuroleptic malignant syndrome via an inadvertent rechallenge in a woman with mental retardation. AB - A case was described in which neuroleptic malignant syndrome reoccurred as the result of an inadvertent rechallenge in a woman with mild mental retardation. This potentially lethal disorder has an incidence of approximately 1% and a mortality rate of about 15%. Individuals with mental retardation are thought to be at greater risk, and some recommendations were offered to prevent recurrence. PMID- 1584032 TI - The Stanford-Binet: Fourth Edition and form L-M in assessment of young children with mental retardation. AB - The Stanford-Binet Intelligence Scale: Fourth Edition appears to be poorly suited for the intellectual assessment of children less than 5 years old who are thought to have mild mental retardation and for persons of any age who are thought to have severe mental retardation. The reasons for this conclusion were explained and reasons provided that support the continued use of Form L-M when assessing such children or older individuals with mental retardation. PMID- 1584033 TI - Assessing the loneliness of workers with mental retardation. AB - This study was designed to determine whether a reliable instrument could be developed to measure the loneliness experienced by workers with mental retardation. In addition, supervisors were asked to rate subjects on loneliness and four other behavioral subtypes in order to determine whether there was a relation between these ratings and the loneliness questionnaire. Three groups of subjects were assessed: persons with mild, moderate, and severe mental retardation. Results indicated that the Worker Loneliness Questionnaire was a reliable instrument for use with persons with mild and moderate mental retardation. In addition, the results showed that some individuals were lonely; however, this was not a pervasive feeling. The implications for measuring the self-perceptions of individuals with mental retardation were discussed. PMID- 1584034 TI - The failure of prevention or our failure to implement prevention knowledge? PMID- 1584035 TI - Parameter estimation by least-squares methods. PMID- 1584036 TI - Analysis of ligand-binding data with experimental uncertainties in independent variables. PMID- 1584037 TI - Monte Carlo method for determining complete confidence probability distributions of estimated model parameters. PMID- 1584038 TI - Maximum likelihood analysis of fluorescence data. PMID- 1584039 TI - Method of moments and treatment of nonrandom error. AB - If one has a convoluted fluorescence decay and wishes to analyze it for a sum of exponential, then one can begin by asking either of two questions: (1) What sum of exponentials best fits the data? (2) What physical decay parameters gave rise to the data? At first these two questions may sound equivalent; in fact, they represent different philosophical approaches to data analysis. In resolving the first question, one adjusts the decay parameters until a calculated curve agrees within arbitrarily chosen limits to the original data. This is what we did in the fourth section of Table II. The fit obtained was decent, but the resulting parameters were wrong. A more difficult approach is to design a method of data analysis which is intrinsically insensitive to the presence of anticipated errors, aiming directly at recovering the decay parameters without regard to the fit. This is what we have done with the method of moments with MD. If particular errors do not have much effect on the recovered parameters, then such a method of data analysis is said to be robust with respect to those errors. Robust methods are widely used in engineering but have not seen much introduction yet to biophysics. Least-squares, the basis of the commonly used data fitting methods for pulse fluorometry, is nonrobust with respect to underlying noise distributions. Isenberg has shown that least-squares is nonrobust with respect to the nonrandom light scatter, time origin shift, and lamp width errors as well. As shown in Isenberg's paper, as well as here, the method of moments with MD is quite robust with respect to these nonrandom errors. Perhaps question (1) could be modified to include all of the errors that might be present in the data; but then, how would one decide which errors to include and whether an error is present? What fitting criterion would tell one this? Why choose a method which depends so strongly on this information when robust alternatives exist? As a rule, fitting should not be used as a criterion for correct decay parameters, unless all of the significant nonrandom errors have been included in the fit. If one fits the data but has not incorporated an important error, then the best fit will necessarily give the wrong answer. The method of moments provides clear criteria for accepting or rejecting an analysis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1584040 TI - Analysis of discrete, time-sampled data using Fourier series method. PMID- 1584041 TI - Alternatives to consider in fluorescence decay analysis. PMID- 1584042 TI - Global analysis of biochemical and biophysical data. PMID- 1584043 TI - Compartmental analysis of enzyme-catalyzed reactions. PMID- 1584044 TI - Analysis of site-specific interaction parameters in protein-DNA complexes. PMID- 1584045 TI - Analysis of circular dichroism spectra. PMID- 1584046 TI - Fluorescence quenching studies: analysis of nonlinear Stern-Volmer data. PMID- 1584047 TI - Simultaneous analysis for testing of models and parameter estimation. PMID- 1584048 TI - Numerical analysis of binding data: advantages, practical aspects, and implications. PMID- 1584049 TI - Deconvolution analysis for pulsed-laser photoacoustics. PMID- 1584050 TI - Parameter estimation in binary mixtures of phospholipids. PMID- 1584051 TI - Deconvolution analysis of hormone data. AB - Deconvolution analysis of hormone data poses special problems in view of the sparse, noisy, and short data series typically available for analysis; the unknown true nature of the underlying secretory event; and potentially large variations in dissipation or clearance kinetics in different settings. Consequently, deconvolution techniques, which concern themselves with the estimation of hormone secretion and/or clearance based on serial circulating hormone concentration measurements, face a particular challenge. Ideal features of deconvolution algorithms are summarized in Table IV. Specific deconvolution techniques available to analyze hormone data include both waveform-defined procedures and waveform-independent algorithms. These approaches should be viewed as complementary rather than antagonistic. All deconvolution techniques are subject to individual limitations and specific strengths. Independently of the method employed, error propagation is necessary so as to define the statistical uncertainty intrinsic to the estimate of secretion and clearance. Such calculations of experimental uncertainty should include error inherent in the sample collection, processing, and assay as well as error in the kinetic constants and/or anticipated departures of the biological process from the algebraic structure of the convolution formulation. Moreover, more complex convolution statements will be required to describe the full range of behavior of hormone data in a systems view. The applications of such newer convolution methods as well as currently available techniques include model synthesis, model testing, and analysis of the interactions among multiple pulse generators. PMID- 1584052 TI - Dynamic programming algorithms for biological sequence comparison. AB - Efficient dynamic programming algorithms are available for a broad class of protein and DNA sequence comparison problems. These algorithms require computer time proportional to the product of the lengths of the two sequences being compared [O(N2)] but require memory space proportional only to the sum of these lengths [O(N)]. Although the requirement for O(N2) time limits use of the algorithms to the largest computers when searching protein and DNA sequence databases, many other applications of these algorithms, such as calculation of distances for evolutionary trees and comparison of a new sequence to a library of sequence profiles, are well within the capabilities of desktop computers. In particular, the results of library searches with rapid searching programs, such as FASTA or BLAST, should be confirmed by performing a rigorous optimal alignment. Whereas rapid methods do not overlook significant sequence similarities, FASTA limits the number of gaps that can be inserted into an alignment, so that a rigorous alignment may extend the alignment substantially in some cases. BLAST does not allow gaps in the local regions that it reports; a calculation that allows gaps is very likely to extend the alignment substantially. Although a Monte Carlo evaluation of the statistical significance of a similarity score with a rigorous algorithm is much slower than the heuristic approach used by the RDF2 program, the dynamic programming approach should take less than 1 hr on a 386-based PC or desktop Unix workstation. For descriptive purposes, we have limited our discussion to methods for calculating similarity scores and distances that use gap penalties of the form g = rk. Nevertheless, programs for the more general case (g = q+rk) are readily available. Versions of these programs that run either on Unix workstations, IBM-PC class computers, or the Macintosh can be obtained from either of the authors. PMID- 1584053 TI - Artificial neural networks. PMID- 1584054 TI - Fractal applications in biology: scaling time in biochemical networks. PMID- 1584055 TI - Use of weighting functions in data fitting. PMID- 1584056 TI - Analysis of residuals: criteria for determining goodness-of-fit. PMID- 1584057 TI - Is endothelium necessary for transmural pressure-induced contractions of bovine truncal lymphatics? AB - The purpose of this study was to investigate the role of the endothelium in regulating lymphatic contractile activity in bovine mesenteric truncal lymphatics. To test the effects of endothelial denudation on lymphatic pumping, bovine lymphatics were suspended in an organ bath preparation with the vessels cannulated at both inflow and outflow ends. By raising the heights of the Krebs reservoir and the outflow catheters appropriately, a transmural pressure could be applied to the vessels. The relationship between transmural pressure and fluid pumping is expressed as a bell-shaped curve with pumping increasing up to a peak pressure (between 8 and 12 cm H2O), and declining at pressures above this level. We compared pressure/flow curves in endothelium-intact and endothelium-denuded vessels. Chemical methods to remove the endothelium were attempted (collagenase and dispase) but were unsuccessful since they resulted in inhibition of all contractile activity including that induced with KCl. A technique using suture silk (3-O to 6-O) threaded into PE 50 or PE 20 polyethylene catheters with a loop at one end proved to be effective. By passing the catheter with its exposed loop of silk through the lymphatic ducts and imparting a twisting motion, we were able to remove the endothelium and preserve the smooth muscle responses to KCl. Transmission electron microscopy as well as silver staining techniques confirmed that all of the endothelium had been removed leaving the subendothelium and smooth muscle undamaged. We established that removal of the endothelium had no effect on lymphatic pumping. Pumping could not have occurred without the normal function of the one-way valves indicating that the denudation procedures did not damage these elements. Maximum flow rates and the transmural pressures that induced peak flows were similar in the two groups. We conclude that the pumping activity of bovine mesenteric truncal lymphatics in response to transmural pressure changes does not depend on an intact endothelium. PMID- 1584058 TI - Microvascular morphometry in primate diaschisis. AB - Focal cerebral ischemia was produced in monkeys by transorbital occlusion of the right middle cerebral artery. Following this, in one group of animals the total microvasculature, including both perfused and nonperfused vessels of the opposite caudate nucleus and insula, was examined by alkaline phosphatase staining of the endothelium. In another group, the patency of the microvascular bed was visualized by india ink perfusion. The number, diameter, and length of visualized vessels were measured by means of a Wild ASBA image analysis system. The perfused patient microvascular bed was significantly reduced in both insula and caudate nucleus in the supposedly normal left side, although the total microvascular volume showed an increase at 4 and 12 hr in the insula and at 48 hr in the caudate nucleus. Reduced perfusion in the hemisphere opposite to the occluded middle cerebral artery provides an anatomical substrate for the phenomenon of "diaschisis." PMID- 1584059 TI - Role of the myogenic mechanism in the genesis of microvascular oscillations (vasomotion): analysis with a mathematical model. AB - The possibility that spontaneous oscillations in microvessel caliber, called vasomotion, arise from the activity of the local myogenic mechanism is analyzed in this work using an original mathematical model. According to experimental results, the model assumes that the myogenic response in microcirculation (transverse arterioles and terminal precapillary-postcapillary microvessels) is characterized by both a static and a dynamic (i.e., rate-dependent) component. Computer simulations demonstrate that the myogenic mechanism of action, thanks to its strong rate-dependent component in terminal arterioles, can produce vascular instability and oscillations of vessel caliber without the need to assume the existence of a local pacemaker in smooth muscle cells. Moreover, these oscillations turn out similar, both in frequency and in shape, to those experimentally observed in microvascular networks. Finally, according to experimental data, several kinds of vasodilatory stimuli (such as arterial hypotension, increase in the tissue metabolic rate, and postischemic reactive hyperemia) cause stoppage of vasomotion and stabilization of vessel caliber. PMID- 1584060 TI - Acute endothelial cell contraction in vitro: a comparison with vascular smooth muscle cells and fibroblasts. AB - The contractile responses of cultured rat and calf endothelial cells (EC), vascular smooth muscle cells (VSMC), and fibroblasts (FB) to vasoactive mediators (thrombin, serotonin, bradykinin, and histamine), forskolin, and cytochalasin B were compared. Cells were grown on a pliable silicone membrane, and contraction was assessed, using time-lapse video microscopy, by recording changes in the wrinkling of the silicone as the cells exerted tension on the surface. We found that all cells contracted in the presence of serum or thrombin and that VSMC and FB also contracted with serotonin stimulation. Bradykinin and histamine were not contractants in this system. Discrepancies between these results and reports of changes in permeability of endothelial layers in vitro and in vivo may be due to (1) the vascular segment from which EC were studied or (2) the possibility that certain mediators may provoke a noncontractile response that results in gap formation. Thus changes in vascular permeability, which occur during inflammation, may have both contractile and noncontractile components. Forskolin, known to indirectly inhibit myosin light-chain kinase activity, and cytochalasin B were potent relaxants, suggesting a similar smooth muscle-like contractile mechanism for all three cell types. PMID- 1584061 TI - Microvascular architecture in rat soleus and extensor digitorum longus muscles. AB - Microvascular architecture was investigated in the slow-twitch soleus (SOL) and fast-twitch extensor digitorum longus (EDL) muscles. Rats (n = 5) were anesthetized and papaverine was infused into a carotid artery cannula to induce vasodilation. Microfil casting compound was then infused at an inflation pressure (caudal artery) of 100 mm Hg. Bilateral SOL and EDL muscles were excised 24-72 hr postcasting, dehydrated in ethanol, and cleared in methyl salicylate. Branch frequencies (BR) and segment lengths (SL) of intramuscular arterioles and venules were quantified along primary (1 degree), secondary (2 degrees), and tertiary (3 degrees) order microvessels using microscopy. In both muscles, BR decreased with increasing vessel order. Regional differences in network organization were observed within the EDL muscle. SL of 1 degrees arterioles was 47% shorter in the SOL muscle indicating more compact microvascular networks compared to the EDL muscle. These findings provide a structural basis for reported differences in blood flow between the SOL and EDL muscles at rest and during exercise. PMID- 1584062 TI - Vasoconstrictor effects of endothelin-1 on myocardium microcirculation studied by the Langendorff perfusion method: differential sensitivities among microvessels. AB - An intravital fluorescence microscope system was used to investigate the pharmacological effects of endothelin-1 (ET-1) on the coronary microcirculation in the isolated beating hearts of rats. The heart was perfused by retrograde aortic steady flow with an oxygenated Krebs-Ringer solution containing FITC dextran. Changes in diameters of coronary microvessels accompanying the cumulative injection of ET-1 in the perfusate were observed and recorded with a video camera system. Coronary perfusion pressure was also measured during each experiment. Bolus injections of ET-1 (1-300 pmole) elicited a dose-dependent increase in perfusion pressure from 54 +/- 6 mm Hg (mean +/- SEM; n = 10, before the ET-1 injection) to 144 +/- 9 mm Hg (n = 8, at the ET-1 dose of 300 pmole). A dose-dependent narrowing of microvessels was also observed. This vasoconstriction was especially prominent in small-sized arterioles; the maximum vasoconstriction of the smaller arterioles was significantly higher than that of the larger arterioles (P less than 0.05). The response induced by ET-1 dose of 3-10 pmole was significantly larger in arterioles than in postcapillary venules in the diameter range between 10 and 40 microns. The vasoconstriction produced by ET-1 was inhomogeneous. Some part of bifurcations of arterioles showed a prominent localized vasoconstriction, and occasionally showed a complete luminal obstruction. Such a segmental vasospasm might be attributed to localized sensitivities of arterioles to ET-1. These findings suggest that ET-1 may have an important role in governing the coronary resistance and regulating the capillary flow in the myocardium. PMID- 1584063 TI - Candida albicans adherence to endothelial cells. AB - Mechanisms of adherence to vascular endothelial cells by microorganisms on a molecular level can be elucidated by using monoclonal antibodies, purified cell wall constituents, and receptor analogues. Since these agents are expensive and available in limited quantities, a microsystem for probing adherence mechanisms to these cells has become essential. We studied techniques to accurately quantify the adherence of L-[35S]methionine-labeled Candida albicans to human umbilical vein endothelial cells in a 96-well microtiter plate system while avoiding specific problems related to Candida coadherence and avid binding to plastic. The endothelial cells were grown on a collagen matrix in individually detachable microwells enabling the determination of the number of adherent organisms from radioactive counts of the entire well. This procedure has the critically important advantage of obviating the need to remove adherent Candida from the wells. Expressing adherence to endothelial cell monolayers as the percentage of total organisms added to each well significantly decreases the variability of the assay. PMID- 1584064 TI - Response of rabbit ear microvasculature to total body cooling as observed through a new implantable window. AB - A new implantable window was developed in order to study the native microcirculation of the rabbit ear. The responses of the ear microvasculature to total body cooling were studied before and after implantation of the window. No differences were found between arteriolar and venular vasoconstriction with cooling before and after implantation of the window. Arteriolar constriction was significantly greater than the venular response both before and after placement of the window (P = 0.014). Surface skin temperature of the instrumented and control ears was similar at room temperature (35.2 +/- 2.6 versus 36.1 +/- 1.0 degrees, respectively; P = 0.280); however, the instrumented ear was slightly warmer during cooling (17.9 +/- 1.9 versus 15.2 +/- 3.1 degrees; P = 0.024), suggesting increased blood flow in the instrumented ear. Details of construction and implantation of the window are described. PMID- 1584065 TI - Strobe epi-illumination of fluorescent beads indicates similar velocities and wall shear rates in brain arterioles of newborn and adult mice. PMID- 1584066 TI - A monoclonal antibody specific for conidia and mycelium wall layer of Penicillium and Aspergillus. AB - A monoclonal antibody was obtained from BALB/c mice immunized with Penicillium frequentans mycelium. The specificity of the antibody was evaluated by enzyme linked immunosorbent and indirect immunofluorescence assays against the same mycelium. This IgM antibody cross-reacted with various strains of the Penicillium and Aspergillus genera. By indirect immunofluorescence assays, the antibody was able to stain about 10% of Penicillium and Aspergillus conidia, but major part of conidia did not absorb the fluorescence-labeled antibody before swelling. During germination of P. frequentans conidia, the germ tube wall which constitutes a continuation of an inner wall layer was also stained. During germination of P. griseofulvum, the protrusion of the germ tube wall was not always recognized by the antibody because the germ tube wall was constituted by a continuation of an outer spore wall layer. The study of the staining patterns of the spores and the protrusions suggests that the antibody specifically recognizes an antigen of the inner spore wall layer. The monoclonal antibody reacts with extracellular galactomannans produced by genera Aspergillus and Penicillium but is not directed against beta-(1,5)-linked galactofuranose units. PMID- 1584067 TI - A unique monoclonal antibody that recognizes mature p17 of HIV-1 but not its precursor. AB - The entire and partial gag regions of human immunodeficiency virus type 1 (HIV-1) were overproduced in Escherichia coli and used for epitope mapping of antibodies against p17. We found that a mouse monoclonal antibody to p17, V17 recognizes the mature p17 but not the unprocessed Gag proteins containing the entire p17 moiety. Further analysis revealed that V17 recognizes the C-terminal 12-amino-acid region of p17 having free C-terminus. This monoclonal antibody may be useful for monitoring the maturation of virus particles. PMID- 1584068 TI - Detection and quantitative assessment of a Vibrio cholerae O1 species in several foods by a novel enzyme immunoassay. AB - A selected antibody enzyme immunoassay (SAEIA) for the general detection of Vibrio cholerae O1 species has been developed using the immunological reagents of a rabbit antiserum specific for V. cholerae O1 classical Inaba 569B and immobilized cell fragments of V. cholerae O1 El Tor 85P6, and beta-D galactosidase-labeled goat anti-rabbit immunoglobulin G as tracer. The SAEIA was specific for V. cholerae O1 species and showed low cross-reaction values to other microorganism species tested including Vibrio parahaemolyticus. The detection limit of the SAEIA was 4,500 cells per assay for all the 13 strains of V. cholerae O1 examined. Quantitative comparison on the growth of the El Tor 85P4 in several foods cultured for 24 hr were studied using the SAEIA. Preceding the experiments, little inhibition of every food homogenate for the measurement of the SAEIA was first demonstrated and then the homogenate was directly used for an assay sample. The interaction of the growth of Escherichia coli to that of V. cholerae O1 in a food was also found to be little under the mixed culturing of both bacteria using the SAEIA. PMID- 1584069 TI - Detection and discrimination of Mycoplasma pneumoniae and Mycoplasma genitalium by the in vitro DNA amplification. AB - By using the primers designed on the bases of the sequences of the 16S rRNA genes of Mycoplasma pneumoniae and Mycoplasma genitalium, respectively, specific and sensitive in vitro DNA amplification assay system for the detection and discrimination of these two mycoplasmas was established. The detection limit of the assay was 100 cells for M. pneumoniae and 1,000 cells for M. genitalium. Neither other human mycoplasmas nor oral bacteria existing in human saliva showed any cross-reactions with these primers. PMID- 1584070 TI - Clostridium botulinum type C in healthy swine in Japan. AB - Healthy cattle and swine bred in a district of Japan were examined for the presence of Clostridium botulinum in their liver. Liver specimens were cultivated in chopped meat-glucose medium and the cultures were examined for botulinum toxin. In cattle, none of the cultures of 100 liver specimens yielded the toxin. In swine, however, C1 or C2 toxin was demonstrated in 8 of 100 liver specimens from 36 farms. One of the five farms where the carrier-state swine were present was surveyed for about 2 years to determine whether the carrier-state was transient or resident. C. botulinum type C was found in swine livers and feces, and environmental specimens at extremely high rates during the surveillances, with 76% of specimens yielding botulinum toxin following the culture. These data suggest that it is not uncommon for healthy swine to carry C. botulinum type C in the liver and that there is a close relationship between C. botulinum carrier state in swine and the presence of this organism in their raising environments. In 20 cattle and 20 swine suffering from parturient paresis of unknown etiology no evidence for involvement of C. botulinum type C was obtained. PMID- 1584071 TI - Some improved versions of methods for the indirect detection of staphylococcal protein A gene expressed in Escherichia coli. AB - Several versions of methods for the indirect detection of expression of staphylococcal protein A gene (spa) in Escherichia coli (E. coli) were devised by making use of biological properties of staphylococcal protein A (SpA). i) Hemagglutination of sheep red blood cells (SRBC) sensitized with anti-SRBC antibodies using heat-treated spa-transformed E. coli organisms; Native spa transformed E. coli organisms did not agglutinate the sensitized SRBC. The heat treatment (60 C, 4 hr) of the transformants, however, caused positive hemagglutination like SpA-positive Staphylococcus aureus (S. aureus) organisms. ii) Halo formation around colonies on agar plates containing normal dog serum, which is originally used for the detection of SpA of S. aureus. A mutant strain NMJ was isolated, which showed formation of the halo of precipitate due to interaction between immunoglobulin and SpA. iii) A new version of immunodetection; After lysis of the transformants grown on a nitrocellulose membrane by alkali, SpA could be directly detected by immuno-detection procedures after inactivation of endogenous peroxidase in bacteria by phenylhydrazine and hydrogen peroxide. PMID- 1584072 TI - Detection of cholera toxin by a highly sensitive bead-enzyme linked immunosorbent assay. AB - A bead-enzyme linked immunosorbent assay (bead-ELISA) for detection and quantification of cholera toxin (CT) in broth cultures of Vibrio cholerae O1 has been developed. Under optimal buffer and pH conditions the bead-ELISA could consistently detect 40 pg/ml of CT. None of the ingredients of commonly used media for in vitro culture of V. cholerae O1 hindered the performance of the bead ELISA. Evaluation of the sensitivity and specificity of the bead-ELISA against the commonly used reversed passive latex agglutination (RPLA) test for detection of CT was performed using a collection of 239 strains of V. cholerae O1 (including both biotypes and serotypes) which were examined by a gene probe encoding for the A1 subunit of CT. Although both the assays were highly specific, the bead-ELISA was more sensitive than the RPLA. Quantification of CT by the bead ELISA revealed that the concentration of CT produced by the strains of V. cholerae O1 which were negative by the RPLA was lower than 1 ng/ml and therefore below the minimum detection ability of the RPLA. The bead-ELISA is a simple, specific and highly sensitive assay for routine detection of CT and is recommended for routine use in clinical microbiology laboratories. PMID- 1584073 TI - Synthetic oligonucleotides with particular base sequences from the cDNA encoding proteins of Mycobacterium bovis BCG induce interferons and activate natural killer cells. AB - Thirteen kinds of 45-mer single-stranded oligonucleotide, having sequence randomly selected from the known cDNA encoding BCG proteins, were tested for their capability to augment natural killer (NK) cell activity of mouse spleen cells in vitro. Six out of the 13 oligonucleotides showed the activity, while the others did not. In order to know the minimal and essential sequence(s) responsible for the biological activity, 2 kinds of 30-mer and 5 kinds of 15-mer oligonucleotide fragments of an active 45-mer nucleotide were tested for their activity. One of the 30-mer oligonucleotides, designated BCG-A4a, was active, but the other 30-mer was inactive. All of the 15-mer oligonucleotide fragments were inactive. The BCG-A4a also stimulated the spleen cells to produce interferon (IFN)-alpha and -gamma. An experiment using anti-IFN antisera showed that the NK cell activation by the oligonucleotide was ascribed to the IFN-alpha produced. It was noticed that all of the biologically active oligonucleotides possessed one or more palindrome sequence(s), and the inactive ones did not, with an exception of a 45-mer inactive oligonucleotide containing overlapping palindrome sequences (GGGCCCGGG). These findings strongly suggest that certain palindrome sequences, like GACGTC, GGCGCC and TGCGCA, are essential for 30-mer oligonucleotides, like BCG-A4a, to induce IFNs. PMID- 1584074 TI - Hepatitis E virus: cDNA cloning and expression. AB - Viral hepatitis E is endemic, frequently provoking epidemic outbreaks in many developing countries. We have attempted to clone the viral genome and to develop an antibody assay system. A lambda gt11 cDNA library was constructed from the bile juice containing putative causative viruses and was immunoscreened by the antisera obtained from patients and monkeys infected with hepatitis E. Three virus-specific clones were isolated and were revealed to overlap one another in sequence, with 1,459 nucleotides in total length. These clones direct the synthesis of polypeptides probably having common immunological epitope(s). Immunoplaque assay revealed the occurrence of antibodies against this epitope in the sera from experimental monkeys with the convalescent phase and from patients of Myanmar, Nepal and India. The data indicate that the cDNA fragments are useful for immunodiagnosis of hepatitis E. PMID- 1584075 TI - Correlation between increased susceptibility to primary Toxoplasma gondii infection and depressed production of gamma interferon in pregnant mice. AB - To explore a possible mechanism of pregnancy-associated suppression of T cell mediated immunity to Toxoplasma gondii, acquired resistance and gamma interferone (IFN-gamma) production in pregnant mice were compared with those in virgin mice after infection with the S-273 strain of this protozoan parasite. The 50% lethal dose of this strain was less than 200 tachyzoites for pregnant mice and 2,800 organisms for virgin controls. Toxoplasma-induced production of both IFN-alpha and IFN-gamma in the bloodstream of pregnant mice was significantly depressed as compared with that in virgin controls. The administration of recombinant murine IFN-gamma (rMuIFN-gamma) resulted in a significant decrease of mortality and parasitic growth in the organs of pregnant mice infected with a lethal dose of S 273 strain tachyzoites. Thus, the impairment of T cell-mediated immune responses was evident in pregnant mice from the impaired IFN-gamma-generating capacity and poor survival rate after primary infection with Toxoplasma. When mice with chronic Toxoplasma infection were injected with specific antigen, the resultant production of IFN-gamma was also significantly suppressed during pregnancy. However, there was no direct correlation between the serum levels of IFN-gamma and susceptibility to reinfection, since the mortality rate of chronically infected pregnant mice after the challenge with the high virulent RH strain was not significantly higher than that of virgin controls. PMID- 1584076 TI - A broad-host-range vibriophage, KVP40, isolated from sea water. AB - A broad-host-range vibriophage, KVP40, was isolated from sea water by using Vibrio parahaemolyticus 1010 (EB101) as the indicator host. The host range of KVP40 extended over at least 8 Vibrio and 1 Photobacterium species. KVP40 was a large tailed phage containing double-stranded DNA and belonged to Ackermann's morphotype A2. KVP40 DNA was cleaved by 11 different type II restriction endonucleases including EcoRI and HindIII, but not by 17 other enzymes including BamHI, KpnI and SalI. PMID- 1584077 TI - Acceleration of adenovirus replication and increased virion production by treatment with the steroid hormone 17 beta-estradiol. AB - We report here that concentration of an estrogen known to promote enhanced transformation and to increase oncogenicity of rat embryo cells, accelerate the production and increase the yield of progeny virions in adenovirus type 12 (Ad 12)-infected HEp-2 cells. Further, measurement of the incorporation of radioactive RNA and DNA precursors indicated that macromolecular synthesis in the estrogen-treated, infected cells was accelerated. Possible explanations for this observation are discussed. PMID- 1584078 TI - Separate isolation of Clostridium difficile spores and vegetative cells from the feces of newborn infants. AB - A modified taurocholate-cefoxitin-cycloserine-fructose agar medium, pH 5.5, on which vegetative cells alone could grow, was newly devised for separate isolation of Clostridium difficile vegetative cells and spores from feces. The ratio of C. difficile-positive feces from healthy newborn infants younger than 10 days of the age was 30.8%, and 93.3% of feces from healthy infants older than 20 days were positive for C. difficile. C. difficile spores alone were detected in twenty-one samples (75%) of C. difficile-positive Twenty-eight specimens. Only 10.7% (3/28) C. difficile vegetative cells alone were detected. C. difficile spores alone were detected in one of nine healthy adults. These collective results offer potential explanations for high frequent isolations of C. difficile from newborn infants without occurrence of pseudomembranous colitis. PMID- 1584080 TI - A latex agglutination test for the detection of Mycoplasma pneumoniae in respiratory exudates: a comparative study with a commercially available DNA-probe test. AB - We prepared polyclonal antibody specific to Mycoplasma pneumoniae. Using this antibody, we developed a latex agglutination test (LAT) for detecting the organism in respiratory exudates as rapid diagnosis of M. pneumoniae infection. Further, LAT was compared with DNA-probe test (DP) which was the only commercially available test for the rapid detection of the organism. In LAT, both M. pneumoniae and M. genitalium give positive agglutination, but the titer of M. genitalium was significantly lower than that of M. pneumoniae. The detection limit of LAT was 2 x 10(5) CFU/ml and that of DP was 5 x 10(4) CFU/ml in vitro. It was considered that target molecules in LAT were accumulated in the pharyngeal portion of the patients, because of their long half-life at 37 C. However, ribosomal RNA which was target molecule in DP was destroyed at 37 C much sooner, and the accumulation could not be expected. Actually, positive rate in LAT was higher than that in DP among clinical specimens in which M. pneumoniae was detected by culture method. The procedure of LAT is much easier and more rapid than that of DP in which radioactive isotope is required. LAT could be the choice of test for rapid diagnosis of M. pneumoniae infection. PMID- 1584079 TI - Genetic and biochemical analysis of ribosomal proteins of minocycline-susceptible and -resistant Mycobacterium smegmatis. AB - A minocycline (MINO)-resistant mutant was isolated from Mycobacterium smegmatis strain Rabinowitschi. Polypeptide synthesis in the cell-free system prepared from the mutant was resistant to minocycline (MINO) because of alterated 30S ribosomal subunits. Upon two-dimensional gel electrophoresis, two proteins of 30S subunit were found to be altered. MINO resistance phenotype was transferred by mating to the recipient strain P-53. MINO resistance phenotype of a recombinant thus obtained was transferred by a different mating system to the recipient strain Jucho, once again. Ribosomal proteins of each of the donors, recipients and recombinants were analyzed and compared on 2-dimensional (2D) electrophoresis. Approximately 50 ribosomal proteins were observed in 70S ribosomes. Some proteins were differently electrophoresed in different strains. The 30S ribosomal subunits contained at least 19 proteins and 50S ribosomal subunits contained at least 23 proteins. Some proteins were easily washed off during dissociation of subunits in sucrose gradients. At least one protein (designated F) in both subunits was observed at the same position. One protein designated C in 30S subunits could be co-transferred to the recipient cells together with resistance phenotype at the frequency of 100% in the 30 recombinants examined so far. The other protein designated D in 30S subunits could be transferred at the frequency of 86-88%. Three other proteins in 50S subunits could be co-transferred to the recipient strain at a lower frequency. Minocycline resistance, therefore, could be mapped close to genes encoding the structure of ribosomal proteins in M. smegmatis. PMID- 1584081 TI - Partial characterization of coliphage WPK and a comparison with coliphage T3. AB - Coliphage WPK was originally isolated from sewage in Kiel, Germany, because its plaque diameter continued to expand for days. Electron microscopy revealed an isometric capsid with dimensions of 54 nm between opposite apices, and a short, noncontractile tail 16 nm long, placing phage WPK into morphogroup C1. The nucleic acid of phage WPK was linear double stranded DNA. The host ranges of phages WPK and T3 were identical. Of ten E. coli strains tested for host range, two were resistant and of eighteen other Enterobacteriaceae only four were susceptible. Seven gram-negative species which are not members of the Enterobacteriaceae were refractory. However, there were differences in plaque morphology and plaque expansion between the two phages. Phage T3 plaques expanded for at least seven days on E. coli B only, while phage WPK plaques expanded for at least seven days on four strains of E. coli. The buoyant density of WPK, determined by isopycnic density gradient centrifugation in CsCl, was 1,508 g/ml which was significantly different than that of T3 at 1.493 g/ml (P less than 0.05). Phage-encoded proteins were examined for each phage using [35S]methionine incorporation, SDS-PAGE, and autoradiography. Of thirty proteins identified in phage WPK and twenty-eight in phage T3, only fourteen were of the same size in both. We concluded that phage WPK was distinct, but related to T3. PMID- 1584082 TI - Interactions between immune-stimulating complexes (ISCOMs) and peritoneal mononuclear leucocytes. AB - Studies were undertaken in mice using immune-stimulating complexes (ISCOMs) or micelles prepared from envelope glycoproteins of human influenza virus (PR8) and matrix (i.e., ISCOM skeleton without incorporated antigen). Electron microscopic studies showed that ISCOMs, in contrast to micelles, have a remarkable affinity for cell membranes and seem to rapidly promote their own internalization by cells to which they adhere. PR8 ISCOMs, but not matrix nor micelles, significantly increased the expression of membrane Ia by peritoneal mononuclear leucocytes 24 hr after intraperitoneal immunization. PMID- 1584083 TI - [An evaluation of the biochemical typing of Klebsiella cultures]. AB - The paper deals with the results of analysis of 219 strains of Klebsiella using 12 tests--fermentation of adonite, asparaginic acid, sodium citrate, dulcite, d tartrate, glutamic acid, inosite, L-proline, sodium malonate; reactions with methyl red, Foges-Proscauer, with 5-ASA. A scheme for determining fermentovars of Klebsiella is suggested which includes the tests--fermentation of adonite, dulcite, d-tartrate, glutamic acid; color reaction with 5-ASA. The groups of Klebsiella different in origin are characterized by nonhomogeneous distribution of different fermentovars. The suggested method of biochemical labelling may be one of the basic ones in complex typing of Klebsiella. PMID- 1584084 TI - [The chromatographic properties of the DNA-dependent DNA polymerases from Acholeplasma laidlawii PG-8]. AB - The DNA-dependent DNA-polymerase (DNA polymerase I which is not sorbed on the column with DEAE-cellulose, and DNA-polymerase II, which is absorbed by this column and is eluted from it by 0.3 M of NaCl), have been isolated from Acholeplasma laidlawii PG-8. DNA-polymerase I in homogeneous state was obtained as a result of the stepwise treatment by heparin-sepharose (elution at 0.35 M of NaCl) and poly-U-sepharose (elution at 0.3 M of NaCl). It was presented on the electrophoregram by one polypeptide with molecular weight of 72 kDalton. The second form of DNA polymerase was also obtained in homogeneous state as a result of sequential treatment on heparin-sepharose (elution at 0.3 M of NaCl) and on poly-A-sepharose (elution at 0.25 M of NaCl): the protein which had manifested polymerase activity was a polypeptide with molecular weight of 45 kDalton. PMID- 1584085 TI - [RNAse substrate specificity in Acholeplasma laidlawii PG-8]. AB - A substrate specificity of RNAses of A. laidlawii PG-8 to polynucleotides - poly (C), poly (U), poly (A) has been studied. Due to the data obtained both intracellular and extracellular RNAses of A. laidlawii possess similar specificity to different polynucleotides. Both RNAses preferentially break cytidine-bonds. Specificity of the studied enzymes in respect to polyuridylic and polyadenylic acids was less expressed. PMID- 1584086 TI - [The destruction of diethylene glycol by a Pseudomonas putida BS-2 culture]. PMID- 1584087 TI - [The bacterial destruction of glycols]. PMID- 1584088 TI - [The sulfate-reducing capacity of bacteria in the genus Pseudomonas]. AB - Active sulphate-reducing microorganism which belongs to the genus Pseudomonas has been distinguished and described. The culture is a facultative aerobe, optimum Eh is -170-180 mV. Pseudomonas sp. being cultivated under strictly anaerobic conditions sulphate-reduction proceeds more intensively than under aerobic conditions. This fact should be taken into account under treatment of industrial sewage. PMID- 1584089 TI - [The microbiological and pathomorphological characteristics of Klebsiella infection]. AB - Biological properties of 350 strains of Klebsiella pneumoniae isolated in newborns during the outbreak of intrahospital infection have been studied. Experimental infection with isolated strains of a similar plasmid profile is simulated, interrelation between the presence of plasmids and ability of the strain to induce generalized Klebsiella infection is shown. Pathological processes in the newborns with generalized infection and in animals with the reproduced experimental Klebsiella infection are shown to be similar in principle. PMID- 1584090 TI - [The mechanisms of Proteus mirabilis resistance to the bactericidal action of blood serum]. AB - When studying sensitivity of Proteus mirabilis to bactericide effect of blood serum the resistance to alternative way of the complement activation was found in a number of strains. The population of cells with morphologically determinable changes of the surface structures resistant to bactericide effect of the serum is formed as affected by the blood serum of the culture P. mirabilis. Proteus proteases capable to inactivate the complement components are one of the factors of P. mirabilis resistance to bactericide effect of the complement. PMID- 1584091 TI - [Phagocytosis and the antiphagocytic factors in mycobacterial infections]. AB - Peculiarities of phagocytosis of pathogenic, conditionally pathogenic ristic is given to antiphagocytic factors which permit some species of these processes with immunity are considered in the paper. A characteristic is given to antiphagocytic factors which permit some species of mycobacteria to avoid protective bactericidal reactions of mammals and to reproduce in phagocytes. Expression of mycobacterial virulence depends on the character of interrelations between the pathogen and cells of reticuloendothelial and immune systems. Interpretation of this mechanism is important in development of the methods of infection control and creation of efficient vaccines. PMID- 1584092 TI - Could a lowered level of uncoupling protein in brown adipose tissue mitochondria play a role in SIDS aetiology? AB - Previously published studies on the relationship between brown adipose tissue thermogenesis and sudden infant death were examined and evidence was collated to support the hypothesis that a decreased level of mitochondrial uncoupling protein (or thermogenin) from the brown fat in some brown fat depots may play a role in SIDS aetiology. PMID- 1584093 TI - The valves, baffles and sphincters of the respiratory system. AB - 'Starting with the integument we see many organs are contractile sacs or multiples thereof which tubes or bags constitute the major part of the entire body' (1). The lungs are a collection of these universal contractile chambers connected in chains and bunches. Such containers typically have muscular walls which stretch and contract to fill and empty also valves or sphincters to regulate the flow between neighbouring chambers. The heart, stomach and uterus are familiar examples. In some systems (e.g. the digestive, renal and respiratory tracts) traffic is also between the milieu exterior and the milieu interior through the organ's wall which is part of the integument. These movements from organ to organ or milieu to milieu involve pressure variations generated by the concerted actions of the mural and valvular muscles. A muscle usually has a doppel-ganger so they are arranged in reciprocating pairs, supinators with pronators, flexors with extensors, chamber walls with sphincters etc. PMID- 1584094 TI - Autonomous informational stability in connective tissues. AB - No coherent theories currently explain connective tissue stability (i.e. 'memory') as well as spatial and temporal adaptability in the face of continual flux of its constituents. Furthermore, explanations of stability based exclusively upon DNA raise certain inherent problems, particularly with the spatial concordance of somatic tissues. As an alternative explanation, it is hypothesized that while connective tissue cells produce extracellular protein precursors through DNA-dependent processes, the assembly, location, orientation and configuration of the extracellular macromolecules as well as their degree of cell attachment depend primarily upon local micro-environmental conditions and/or self-organization rather than strictly cellular processes. The resulting extracellular matrix (ECM) serves as a time- and spatially-variable filter about each cell to afford a relatively consistent micro-environment for all similar cells, regardless of the more variable macro-environment. By insuring a consistent set of signals to the cell, the filter provides a non-genetic memory complementary to genetic memory. The half-lives of constituent molecules define the duration of the filter, allowing the filter to adapt to new environmental demands, yet to maintain a consistent milieu for the cell. The cell/matrix construct permits local, self-optimizing, non-deterministic tissue autonomy obviating the need to postulate certain intricate mechanisms coordinating spatial morphology and temporal behavior. PMID- 1584095 TI - Multiple sclerosis: prevention of serious illness--vision of a desired future for newly ascertained patients. AB - The increased prevalence of MS worldwide and the resultant high frequency of serious illness among young adults urges that the developed methods of prophylaxis are fully tested. Reference is made to the hypothesis of a circulating toxin playing a role in disease development. Insights from basic research now in progress may expand or amend the scenario. This discussion pertains to biological reasoning and a prophylactic treatment which is able to postpone or avoid disability in MS. PMID- 1584096 TI - Albert Einstein's dyslexia and the significance of Brodmann Area 39 of his left cerebral cortex. AB - By his own admission, Albert Einstein, 'started to talk comparatively late ... certainly not younger than three', and also had 'poor memory of words', during his childhood years. If lesions in Brodmann Area 39 of the cerebral hemisphere results in dyslexia, the 1985 report on the study of Einstein's brain that the neuron:glial ratio of Area 39 in the left cerebral hemisphere of the physicist was significantly smaller than that of the control values, provides a neuroanatomical clue to Einstein's childhood dyslexia. Though not discrediting this finding, some questions are raised in this paper regarding the controls employed in this 1985 report (1). PMID- 1584097 TI - A mathematical model for brain edema: the relationship between brain tissue water content and intracranial pressure. PMID- 1584098 TI - The physiological membrane potential as work energy. PMID- 1584099 TI - Immune response: tissue specific T-lymphocytes. AB - The lymphatic system forms a 'blind' plexus of vessels that in general are found in tissue which has an inherently high replicative capacity. It is this system that is responsible for the rapid deployment and circulation of tissue-specific T lymphocytes for the inspection of cell-surface aberrations within the tissue. The presence of tissue-specific T-lymphocytes explains why 90% of lymphocytes are found outside the lymphatic system and why they migrate in a selective manner. The tissue-specific T-lymphocyte is considered to express a common lymphocyte cell surface pattern, the homotype, and a tissue-specific cell-surface pattern, the histotype which may involve MHCA and mHCA. It is the histotypic pattern that is responsible for the tissue specificity of the tissue-specific T-lymphocyte. The presence of tissue-specific T-lymphocytes does pose problems for the immune system. If different tissue-specific T-lymphocytes met within a particular tissue, 'lost' lymphocytes, an immune response will be generated against the intruder (lost lymphocyte), and the intruder will not be able to recruit other immunocompetent cells in that tissue. This immune reaction is an attempt to change the histotypic pattern of the intruder. This situation would explain the autologous immune response. This response however is suppressed in the systemic system by immunosuppressive compounds from the liver. It is only in the tissues that the tissue-specific T-lymphocytes are released from this suppression, in order to initiate immune reactions against aberrant cell-surface patterns. PMID- 1584100 TI - The resonator theory of colour vision. AB - The resonator theory claims that light scattering by the melanin granules of the retinal pigment epithelium causes light to be reflected back through the outer segment of the cones, in a direction opposite that of the incident light. These two opposite directed wave motions may produce standing waves inside the cone outer segment, which then acts as a resonating cavity for light waves. The wavelength specificity of the single cone is determined by the length and the diameter of the cone outer segment. The variation of the length and the diameter of the cone outer segments throughout the retina is then the basis of colour discrimination. PMID- 1584101 TI - The paradoxical effects of dietary fish oil on blood pressure. AB - Dietary fish oil supplementation has received considerable interest as a non pharmacological adjuvant in the treatment of several diseases, especially hypertension. However, epidemiological, clinical, and experimental evidence conflict. A hypothesis is proposed that fish oil, may have a variable effect on vascular reactivity and consequently, blood pressure. A mechanism is proposed and reasons for the variation in the literature suggested. On the basis of this analysis a potentially adverse effect of dietary fish oil on blood pressure in some individuals is suggested. PMID- 1584102 TI - Role played by vasopressin (and of an adrenalpostpituitary imbalance) in the development of cancerous diseases. AB - Several authors have demonstrated that vasopressin (VP) plays a role in the metabolism of various cell lines, cancerous or not, and in particular acts upon the growth and the multiplication of cell cultures. Less known are the data concerning the existence of an adrenal-postpituitary imbalance in favour of VP in cancerous patients. Seeing that adreno-cortical hormones (ACH) are able to exert an inhibiting action on cell multiplication in vitor, a similar effect being very moderate or even absent in vivo, one can see the advantage of taking such effects into account. They allowed us to explain the discrepancy between the in vivo and in vitro effects of ACH, since VP is able to counteract the expected effects of ACH. A model, first empirical, then mathematical, of the so-called adrenal postpituitary system, was proposed for this purpose. It enables us to propose some hypotheses in the fight to escape the action of ACH in cancer. Paradoxically, it seems that a bipolar therapy, using ACH and VP, would be useful in reaching this goal. PMID- 1584103 TI - Potential role of the viral protease in human immunodeficiency virus type 1 associated pathogenesis. AB - Infection with the human immunodeficiency virus type 1 (HIV-1) results in a variety of pathological changes culminating in the acquired immune deficiency syndrome (AIDS). While most of these changes can readily be accounted for either by direct effects of HIV-1 on the immune system or by indirect effects of secondary infectious agents as a result of faulty immune surveillance, the direct cause for a number of disease states, including some neuropathies, myopathies, nephropathy, thrombocytopenia, wasting syndromes and increased incidence of cancers (primarily lymphoma) has remained an enigma. We have recently shown that the HIV-1 protease, a viral encoded enzyme necessary for virus maturation and infectivity, can cleave a variety of host cell cytoskeletal proteins in vitro. Potential substrates for the HIV-1 protease are found in all of the cell types affected in these unexplained diseases. Recent proposals suggest that elements of the cytoskeleton may play an important role in the regulation of large scale genetic regulation. We propose that some of the degenerative changes associated with infection by HIV-1 are a direct consequence of cleavage of host cell cytoskeletal proteins, which in turn may be responsible for the increased incidence of cancer in HIV-1 infected individuals as a result of the perturbation of the regulation of gene expression by cytoskeletal components. PMID- 1584104 TI - Seasonal preovulatory overripeness ovopathy: a reappraisal of the concept. AB - Seasonal Preovulatory Overripeness Ovopathy (SPOO) is one explanation for seasonal variations in the occurrence of congenital anomalies. This concept entails that during some seasons the preovulatory phase of the development of the human egg is lengthened, causing congenital anomalies. Although the concept of SPOO provides an innovative explanation for the etiology of congenital anomalies, its dissemination in the scientific world has been limited. The aim of this paper is to explain this limited dissemination through a critical examination of the concept itself. To do this we analyzed the degree in which this concept has a sufficient informative content and explanatory power, following criteria formulated by Popper. It is concluded that descriptions of the concept of SPOO are ambiguous. Thus the concept cannot be tested and has a limited informative content. The explanatory power of the SPOO concept remains unclear, in itself and relative to competing explanations. Further one of its basic assumptions, seasonal variation of the length of the preovulatory phase due to an endogenous mechanism, has been refuted. Future research should better be directed to causes of preovulatory overripeness ovapathy (OO) other than seasonality. This preovulatory OO offers an innovative view on the etiology of congenital anomalies. PMID- 1584105 TI - New biological approach and solution to SIDS. AB - The toothlessness and, specifically, the oral gap which is present between the lower and upper gums in the oral cavity of the toothless baby, while only temporary anatomical deficiencies, are, nevertheless, very important ones. It is suggested herein that this phenomenon of toothlessness and temporary physical abnormality has the ability to cause sudden infant death syndrome (SIDS) in a significant number of babies in their early months. What follows is a presentation of a new biological approach to the underlying causes of SIDS and, in the Conclusion section, concrete and practical suggestions are given for a completely new method to counteract and neutralize the threatening dangers of SIDS. PMID- 1584106 TI - Immunological correlations between ontogenesis and oncogenesis: theoretical implications and suggestions for tumor immunotherapy. AB - The previously hypothesized paraembryonal nature of tumor cells (1) leads one to suggest, immunologically, the presence in a tumor of two main cell populations: one consisting of either genotypically or phenotypically paraembryonal cells (PECs), with no differentiation MHC (major histocompatibility complex) antigens, and representing the stem tumor cells; the other consisting of phenotypically differentiated-paraembryonal cells (DPECs), with either embryonal or differentiated antigens, rising from neighbour genotypically normal cells induced by PECs. PECs, without MHC antigens, might escape alpha beta TCR (T-cell alpha beta receptor) lymphocyte immunosurveillance, since alpha beta TCR T-cells recognize only MHC-restricted antigens, such as DPEC antigens. On the other hand, PECs might be recognized by gamma delta TCR lymphocytes, known to constitute a more primitive immunosurveillance system, able to recognize non-MHC-restricted antigens. On this ground, several immunological aspects of the tumors are analysed and suggestions for a more effective tumor immunotherapy are given. PMID- 1584107 TI - Poliomyelitis: the role of diet in the development of the disease. PMID- 1584108 TI - Insomnia-coma and auto-electrocution complicating general anesthesia. Incidental factors which also cause cerebral, respiratory and cardiac arrest. AB - Whatever induces general anesthesia, i.e. cerebral arrest, tends to cause respiratory and cardiac arrest also. However, general anesthesia does not necessarily exclude nor block all other mechanisms which can provoke one or more of these three phenomena. Amongst many such more or less equipotent factors are intracranial, intrapleural, intra-abdominal and intratracheal pressures. These mechanical factors occurring but unrecognized in surgical patients cause puzzling complications including, insomnia, coma and unexpected sudden death. PMID- 1584109 TI - Pseudomonas aeruginosa is retained in the bronchi of cystic fibrotics by the increased transepithelial potential. AB - There is no hypothesis which satisfactorily unifies the abnormal secretions of electrolytes in cystic fibrosis (CF) with the thickened mucus and the retention of Pseudomonas aeruginosa (PA). We have shown that mucus becomes opaque and more viscous adjacent to a positive electrode and that PA derived from CF sputum electrophoreses much faster than control PA. We propose that the increased transepithelial potential in CF respiratory tract acts to thicken mucus polymers thereby increasing its viscosity. We also suggest that as the thicker mucus forms on the epithelial surface bacteria with a high electrophoretic mobility (EM) are drawn into it and are thereby selected. PMID- 1584110 TI - [Antibacterial therapy in infectious bronchial diseases. Recommendations of the German League for control of respiratory tract diseases]. PMID- 1584111 TI - [Therapy of drug-induced chronic headache. Recommendations of the German Migraine and Headache Society]. PMID- 1584112 TI - [Liver transplantation. Organ-splitting and live donation]. PMID- 1584113 TI - [Excess caused by excess?]. PMID- 1584114 TI - [Neurotrophic factors. Therapeutic approach in neurodegenerative diseases]. PMID- 1584115 TI - The choice of antibacterial drugs. PMID- 1584116 TI - Comments on "My dear Eve...". Letters of Ernest Rutherford to Arthur Stewart Eve [FONTANUS I, 3-37 (1988), continued in II, 111-138 (1989) and lastly in FONTANUS IV, 69-108 (1991)]. PMID- 1584117 TI - A pencil beam model for photon dose calculation. AB - A method for photon dose calculation in radio therapy planning using pencil beam energy deposition kernels is presented. It is designed to meet the requirements of an algorithm for 3-D treatment planning that is general enough to handle irregularly shaped radiation fields incident on a heterogeneous patient. It is point oriented and thus faster than a full 3-D convolution algorithm and uses the same physical data base to characterize a clinical beam as a full 3-D convolution algorithm. It is shown that photon therapy beams can be characterized with great accuracy from a combination of precalculated Monte Carlo energy deposition kernels and dose distributions measured in a water phantom. The data are used to derive analytical pencil beam kernels that are approximately partitionated into the dose from (i) primary released electrons and positrons, (ii) scattered, bremsstrahlung, and annihilation photons, (iii) contaminating photons, and (iv) charged particles from the collimator head. A semianalytical integration method, based on triangulation of the field, is developed for dose calculation using the analytical kernels. Dose is calculated in units normalized to the incident energy fluence which facilitates output factor calculation. For application in heterogeneous media, a scatter correction factor is derived using monodirectional convolution along the ray path. In homogeneous media results are compared with measurements and in heterogeneous media with Monte Carlo calculations and the Batho method. PMID- 1584118 TI - A general method to perform dose calculations along the axis of symmetrical and asymmetrical photon beams. AB - Many manufacturers of modern linacs provide collimators with jaws that can be set asymmetrically. In the present work, the authors propose the use of a product of four independent output factors related to the four jaws to calculate the reference dose rate of asymmetrical fields. Each of these factors is normalized to the maximum opening of the collimator. A general algorithm for symmetrical and asymmetrical fields is proposed for dose calculation. Calculations have been checked by measurements at the reference depth in a 4-MV x-ray beam. PMID- 1584119 TI - A method of calculating peripheral dose distributions of photon beams below 10 MV. AB - The radiation dose outside the radiotherapy treatment field can be of clinical concern and, therefore, a method of accurately predicting the peripheral doses received by tissues would be beneficial. This paper describes a semiempirical method developed for calculating the peripheral dose received at points outside the collimated field edge for incident photon beams with energies below neutron production thresholds (less than 10 MV). The dependence of the peripheral dose upon depth, distance, field shape and size, azimuthal angle about the central axis, external contour variations, and tissue heterogeneities are accounted for by this calculation. Predictions by this algorithm are compared with measurements and it is shown that the method is capable of reproducing the measured peripheral dose values usually to within the statistical uncertainties of the data. PMID- 1584120 TI - Application of the convolution method for calculation of output factors for therapy photon beams. AB - The output factor for a therapy photon beam is defined as the dose per monitor unit relative to the dose per monitor unit in a reference field. Convolution models for photon dose calculations yield the dose in units normalized to the incident energy fluence with phantom scatter intrinsically modeled. Output factors calculated with the convolution method as the dose per unit energy fluence relative to the calculated dose per unit energy fluence in a reference field could deviate as much as 5% if corrections are not made for perturbations due to treatment head scatter. Significant perturbations are particles backscattered from the collimators to the monitor and photons forward scattered from the filter and collimators in the treatment head. The forward scatter adds an "unmonitored" contribution to the total energy fluence of the beam. A model is developed that describes the field size dependence of these perturbations for conversion of output factors, calculated with the convolution method, to machine output factors as an integrated part in treatment planning. The necessary machine characteristics are derived from measurements of the output in air for a limited set of field sizes. The method has been tested using five different multileaf collimated irregular fields at 6 MV and for a large set of rectangular fields at 5, 6, and 18 MV and found to predict output factors with an accuracy better than 1%. PMID- 1584121 TI - A standard timing benchmark for EGS4 Monte Carlo calculations. AB - A Fortran 77 Monte Carlo source code built from the EGS4 Monte Carlo code system has been used for timing benchmark purposes on 29 different computers. This code simulates the deposition of energy from an incident electron beam in a 3-D rectilinear geometry such as one would employ to model electron and photon transport through a series of CT slices. The benchmark forms a standalone system and does not require that the EGS4 system be installed. The Fortran source code may be ported to different architectures by modifying a few lines and only a moderate amount of CPU time is required ranging from about 5 h on PC/386/387 to a few seconds on a massively parallel supercomputer (a BBN TC2000 with 512 processors). PMID- 1584122 TI - Installation of EGS4 Monte Carlo code on an 80386-based microcomputer. AB - This article presents the considerations and efforts involved to install and fully support the EGS4 radiation-transport Monte Carlo simulation code on an 80386-based microcomputer. It also presents some EGS4 benchmark timing comparisons between this and other computer architectures. PMID- 1584123 TI - Electron beam characteristics of the 50-MeV racetrack microtron. AB - Electron beams in the MM50 racetrack microtron are generated by computer controlled scanning of a well-focused electron pencil beam. The treatment head is optimized to give a minimum of scatter between the source position and the collimator plane by a general minimization of all scattering material in the beam and by replacement of the air in the treatment head by helium, which has a much lower linear scattering power than air. A double-focused multileaf collimator with a 31-cm collimator to patient distance is used both for electron and photon collimation. In general, no extra electron collimation is needed for the standard SSD of 100 cm. To make irregular field collimation at a distance this far from the patient possible, a number of requirements have to be fulfilled regarding the virtual source position and the spatial and angular distribution of the initial electron beam. The virtual source position has been found to be at a fixed position for different irradiation parameters. This is important for the use of the light field in electron beam treatment but also for achieving a high degree of accuracy in the dosimetry. Scatter from the multileaf collimator has not been found to give any significant contribution to the radiation field or to the monitor output factor of the MM50. Experimental dose distribution data on the MM50 have been compared to data both from other types of treatment units and to Monte Carlo simulations. PMID- 1584124 TI - Evaluation of film and thermoluminescent dosimetry of high-energy electron beams in heterogeneous phantoms. AB - Film and thermoluminescent dosimetry (TLD) are investigated in heterogeneous phantoms irradiated by high-energy electron beams. Both film and TLD are practical dosimeters for multiple and moving beam radiotherapy. The accuracy and precision of these dosimeters for radiation dose measurements in homogeneous water-equivalent phantoms has been discussed in the literature. However, film and TLD are often used for dose measurements in heterogeneous phantoms. In those situations perturbations are produced which are related to the density and atomic number of the phantom material and the physical size and orientation of the dosimeter. In our experiments the relative dose measurements in homogeneous phantoms were the same regardless of dosimeter or dosimeter orientation. However, significant differences were observed between the dose measurements within the inhomogeneity. These differences were influenced by the type and orientation of the dosimeter in addition to the properties of the heterogeneity. These differences could be reproduced with Monte Carlo calculations and modeling of the experimental conditions. PMID- 1584125 TI - An electron density calibration phantom for CT-based treatment planning computers. AB - In order to correct for tissue heterogeneities on a voxel-by-voxel basis during CT-based treatment planning, the relationship between the correction factor (CF) and the CT number in Hounsfield units (HU) for the scanner in use must be established. Since the relationship between CF and electron density (rho e) of various materials is well documented, the rho e vs HU is required for direct computation of the correction factors by treatment planning computers. A CT phantom with 18 different tissue substitutes has been used to establish the rho e vs HU relationship. A description of the phantom and its contents is given and the calibration of the CT function of the planning computer is discussed. PMID- 1584126 TI - Correlation of projection radiographs in radiation therapy using open curve segments and points. AB - A method for determining differences in patient position between projection radiographs such as those routinely used in radiation therapy has been developed. Determination of a transformation relating two radiographs permits registration of simulation and portal images and the transfer of information between them. The algorithm is based on spatially registering segments of open curves or points seen on both images, and does not require identification of corresponding curve endpoints. The method as implemented is both fast and accurate. After user definition of the curves or points to be registered, the optimal transformation is calculated in approximately 1 s. Calculational experiments indicate that corresponding points on open curves are registered to better than 2 mm, even when random errors (FWHM 1 mm) in digitization are included. Experiments on the registration of clinical portal and simulation images (pixel size = 0.5 by 0.5 mm) indicate an accuracy on the order of 2 mm or less in translation and 2 deg or less in rotation. Analysis of portal and simulation radiographs of the brain, thorax, and pelvis indicates this algorithm to be robust and clinically applicable. The rapid and accurate registration of portal and simulation images is potentially important in the application of real time portal imaging devices in radiation therapy. PMID- 1584127 TI - Matching photon and electron fields in the treatment of head and neck tumors. AB - Radiotherapy of head and neck tumors frequently involves joining photon and electron fields. In such situations narrow penumbras combined with relatively small positioning errors can lead to significant "hot" and "cold" spots in the vicinity of the join-up. The objective of this work was to devise penumbra spreading techniques which lead to a relatively uniform dose distribution in the join-up region of these fields and which reduce the effect of positioning errors on dose uniformity. A stepped edge attenuator was used to obtain a wider penumbra for the 4-MV x-ray beam and a Lucite scatterer was used for the 10-MeV electron beam. The resulting composite beam profiles from these "modified" abutting photon and electron fields are provided and the effects of positioning errors on dose uniformity across the junction are illustrated. These profiles are compared with those resulting from "unmodified" adjacent electron and photon beams. PMID- 1584128 TI - Beam characteristics of a new model of 6-MV linear accelerator. AB - This paper describes the beam characteristics and dosimetry measurements performed on the 6-MV photon beam of a new model of linear accelerator, three of which were recently introduced and installed in our institution. Percent depth dose and tissue maximum ratio tables for a variety of field sizes and depths, as well as other parameters used for treatment planning are presented. These accelerators are the first of their kind using both hardware and software tools to control interlocks. Checking procedures for these interlocks are available from the authors upon request. Comparison of characteristic parameters between these three new 6-MV linear accelerators and with the 6-MV beams of two other accelerators is also made. PMID- 1584129 TI - Generation of portal film charts for 10-MV x rays. AB - An analytical method to generate portal film charts for 10-MV photon beams, which takes into account the presence of the cassette front screen is presented. The selection of the best film-screen combination was based on the new AAPM recommendations for radiotherapy portal imaging [AAPM Rep. No. 24, AAPM Task Group No. 28 (1987)]: 2-g/cm2-thick copper front screen and 0.4-g/cm2-thick copper rear screen, and X-OMAT TL Kodak unwrapped film. Doses at the film position were measured as a function of patient thickness, field size, air gap, and the results compared well with the doses derived from the analytical method: within +/- 15%. An optical density of 1.6 was selected for construction of the portal film charts. The application of the method for routine treatment planning quality assurance allows a quick and precise determination of the best exposures to the portal films. PMID- 1584130 TI - Dose measurement at high atomic number interfaces in megavoltage photon beams using TLDs. PMID- 1584131 TI - Mechanical and radiation isocenter coincidence: an experience in linear accelerator alignment. AB - As part of the commissioning procedure of a linear accelerator at our cancer center, the defining laser lines were aligned with the optical and radiation isocenter of the linac. When a mechanical checkout jig was set up at the same point, a discrepancy of 4 mm resulted when the gantry was moved from 0 degrees to 180 degrees. Extensive measurements, some with custom-designed devices, confirmed the observations and provided an explanation. Even though the mechanical isocenter is within the specified tolerance of 1-mm radius, the clinically observable discrepancy of 4-mm results from the noncoincidence of the mechanical and radiation isocenters. The clinical significance of the final setup is discussed and future commissioning procedures are recommended. PMID- 1584132 TI - Self-adhesive lead for compensator production and radiation shielding. AB - Sheet lead is a commonly used material for the manufacture of compensators and for radiation shielding. However, it suffers from such problems as nonuniformity of thickness, difficulties in accurate cutting and alignment, and toxicity. A double-sided adhesive lead sheet has been developed which overcomes these problems. PMID- 1584133 TI - Comments on "Induced effects in ionization chamber cables by photon and electron irradiation". PMID- 1584134 TI - Experimental values for P(wall,x) and P(repl,E) for five parallel-plate, ion chambers--a new analysis of previously published data. PMID- 1584135 TI - Neutron induced brachytherapy: a combination of neutron capture therapy and brachytherapy. AB - Brachytherapy is a widely used radiation therapy modality while neutron capture therapy is being intensely studied. These methods provide some advantages, but also have limitations that might be ameliorated by combining them. A technique that uses stable solid seeds or needles of Gd which are irradiated in vivo with neutrons has been evaluated. Monte Carlo calculations show that 5000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm3 with a three plane implant of 9-Gd needles. The tumor to normal tissue advantage of this method is as good as brachytherapy using 60Co seeds. Measurements of prompt gamma dose with films and TLD-700s in a lucite phantom verify the Monte Carlo evaluation. Dose measurements of a Gd needle in air also show that Gd is promising for this form of brachytherapy. PMID- 1584136 TI - Conversion from Cs-137 to Ir-192 for high dose rate remote afterloading: practical considerations. AB - High dose rate (HDR) remote afterloading is increasingly being used to replace many conventional low dose rate (LDR) brachytherapy procedures. Implementation of the microSelectron-HDR with Ir-192 at our facility necessitated this study to obtain equivalent dosimetric distributions with those of our LDR Cs-137 techniques using our current treatment planning system. Three anatomical sites are presented: nasopharynx, esophagus, and uterine cervix. Attention must be given to the anisotropy of Cs-137 tubes when converting to Ir-192; for linear geometries, total equivalent activity may be preserved but the shapes of the resulting isodose curves for Ir-192 are longer than those of Cs-137. In the case of Fletcher-Suit intracavitary treatments of the uterine cervix, the longer contours for Ir-192 in the vaginal ovoids results in higher isodose levels reaching the bladder and rectum. Maintaining the traditional dose levels to these organs is accomplished by modifying the loading of the ovoids to approximately 85% of the corresponding Cs-137 activity. Computerized dosimetry is presented, along with a chart we have devised to easily convert a standard LDR treatment to HDR dwell times. Our results are especially suitable to those users who will continue to make use of their present computer treatment planning system. PMID- 1584137 TI - Interseed effects on dose for 125I brachytherapy implants. AB - Dose calculations in multiseed brachytherapy implants are done by adding the contribution of each individual seed and by assuming that radiation from each seed is unaffected by the presence of the other seeds. To test the validity of this assumption, dose measurements with various configurations of multiseed implants of 125I model 6702 and 125I model 6711 sources were performed. For a linear configuration of three 125I model 6702 seeds at 1-cm separation, with their transverse axes coincident, doses at distances of 3.05 and 5.09 cm from the center along the transverse axis were found to be about 8% lower than the sum of doses from the three individual seeds. However, for three seeds at 1-cm intervals with their longitudinal axes coincident, doses at 3.05 and 5.09 cm distances from the center along the longitudinal axis were found to be about equal to the dose sums from individual seeds. These initial experiments indicated that the magnitude of the interseed effect depends upon the orientation of the seed relative to each other in an implant. To evaluate the importance of this interseed effect for multiseed configurations of 125I model 6702 and 125I model 6711 seeds, dose rates at various distances from a two-plane implant (each plane containing a 3 x 3 array of sources in a 1-cm spacing square grid) were measured in a Solid Water phantom with LiF TLDs. These measurements were carried out in two different planes at different orientations relative to the implant. The average values of the interseed effect at distances ranging from 1 to 7 cm outside the implant were observed to be about the same for 125I model 6702 and model 6711 sources. The mean value of the interseed effect was 6% and the maximum was 12%. On the whole, the interseed effect reduces the dose at the periphery of the iodine implant by 6%. PMID- 1584138 TI - Diode dosimetry of models 6711 and 6712 125I seeds in a water phantom. AB - Two-dimensional relative dose distributions have been measured around 125I brachytherapy seeds. The two seed models studied, models 6711 and 6712, were manufactured by the 3M Company. Silicon detectors immersed in water phantoms were used to measure the dose. A computerized data acquisition system that controlled the radial position of the diode and the angular rotation of the seed, as well as a manually controlled system were used to collect and store the data. Our results show that the two seed models have relative dose distributions which are quite similar; however, the absolute dose distributions are sufficiently different to warrant separate look-up tables for the two seed models. Additionally, our results are compared with dose distribution data previously obtained for the model 6711 seed. PMID- 1584139 TI - Tissue inhomogeneity correction for brachytherapy sources in a heterogeneous phantom with cylindrical symmetry. AB - In brachytherapy it is customary to perform dose calculations for an implant assuming that the tumor and surrounding tissues constitute a uniform, homogeneous medium equivalent to water. In this work, the validity of the above assumption is studied quantitatively for points along the transverse axis of 103Pd, 125I, and 241Am brachytherapy sources, using measured and Monte Carlo calculated dose rates in homogeneous and heterogeneous media with cylindrical symmetry. The irradiation geometry chosen was a single source implanted in a Solid Water phantom which had a 1- or 2-cm-thick cylindrical Solid Water shell replaced by a polystyrene shell. The Monte Carlo simulations were performed using the integrated tiger series CYLTRAN Code. Experimental data were obtained for the same geometry to test the validity of the Monte Carlo calculations for a heterogeneous phantom. Measured dose rates just beyond a 2-cm-thick polystyrene heterogeneity were observed to be greater than those in a homogeneous Solid Water phantom by about 130%, 55%, and 10% for 103Pd, 125I, and 241Am, respectively. Thus the effect of a relatively small polystyrene heterogeneity in Solid Water can be substantial for lower energy photons. This perturbation of dose was found to increase steeply with decreasing energy and increasing size (thickness) of inhomogeneity. A simple dose calculation formalism has been developed to predict dose rate in a heterogeneous phantom with cylindrical symmetry, which uses as input the radial dose functions of the uniform media comprising the heterogeneous phantom. Dose rate predictions using this formalism are in reasonable agreement with the experimental data and the Monte Carlo calculated values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584140 TI - Sampling methods for a matrix ionization chamber system. AB - To achieve increased image acquisition speed or better image quality, several read-out methods for a matrix ionization chamber system have been investigated. In this device, which is applied for portal imaging in radiation therapy, 256 x 256 small liquid-filled ionization chambers are scanned by switching the polarizing voltage applied to rows of chambers. The ionization current of each column is measured by a separate amplifier. In this approach, instead of measuring row by row, more complex switching schemes can be applied for the polarizing voltage. These schemes are useful either for varying speed and spatial resolution of the imaging device or for coded sampling of the ionization signal. The former option allows for doubling or quadrupling the acquisition speed with a small loss in image quality, or for obtaining a large improvement in signal-to noise ratio at the cost of image resolution. In the latter option, coded sampling, the image is reconstructed mathematically from the measured signals. It is shown that in this case the application of Hadamard or derived matrices for sampling leads, under certain circumstances, to a noise reduction in the reconstructed image. PMID- 1584141 TI - A geometric model for measurement of surface distance, surface area, and volume from tomographic images. AB - Surface area and volume are essential measurements in the morphometric assessment of anatomical structures. New algorithms were developed to measure (1) distance along a curve, (2) surface area, and (3) volume using data extracted from tomographic images as a geometrical surface model. The model is a list of coordinates and normal vectors for each voxel or point gathered from the surface of a selected object. The resulting surface-based pointlist is also used for high speed rendering of surfaces. Differential arclength and surface area are measured with high numeric precision by using the absolute value of the maximum component of the unit normal vector (MUNC) to approximate their values. These differential values are summed to measure distance along a curve and surface area. A discrete form of the Divergence theorem, also using the MUNC, is used to calculate volume. The intrinsic accuracy of the measurement algorithms was evaluated using computer generated pointlists of circles, ellipses, spheres, and ellipsoids. Compared to standard measurement techniques, the new algorithms provided the greatest accuracy and least shape-related bias for measurement of distance, surface area, and volume. Feasibility of using the new algorithms to measure physical objects was tested with CT images of spherical, egg-shaped, and irregular shaped objects. The Dividing Cubes algorithm was used to segment and create pointlists from the CT data. Volume and surface area measurements from CT data compared extremely well with reference values for most objects tested (errors less than 2%). PMID- 1584142 TI - A geometric algorithm for medical image correlations. AB - An automatic image correlation algorithm is discussed for the cranial region which is based on the geometric properties of the second moment tensor associated with a volume. The second moment tensor of two identical volumes represented in two different coordinate frames is evaluated to obtain the set of translations, rotations, and anisotropic scaling operators which relate the two coordinate frames. The theory is presented along with a discussion of quantitative error analysis to measure the usefulness of such an algorithm in the clinical setting. PMID- 1584143 TI - Molybdenum metabolism studied by means of stable tracers. AB - An investigation on molybdenum metabolism by administration of molybdenum stable isotopes was performed. Fractional intestinal absorption was determined in animals by the double tracer technique. The investigated subjects were given an enriched solution of Mo-96 orally and, a few minutes later, an enriched solution of Mo-95 intravenously. Blood samples were drawn at different times following the tracer administration. The Mo-95 and Mo-96 contents in plasma samples were determined by proton nuclear activation. The described methodology offers a means for the study of molybdenum metabolism in humans without radiation risk. PMID- 1584144 TI - An AC biosusceptometer to study gastric emptying. AB - A simple AC susceptometer was developed to study the gastric emptying when test meals labeled with 10% of a harmless magnetic tracer were ingested. The instrument allows the determination of T 1/2 of the stomach emptying with good precision compared to measurements with gamma camera and 99m Tc in the test meal. PMID- 1584145 TI - Imaging characteristics of different mammographic screens. AB - A study of mammography systems with green-emitting screens was conducted to determine how the image quality parameters (apart from dose requirement), such as modulation transfer function (MTF) and Wiener spectrum (WS), depend on the dye content of the compound and coating weight of the screen. In addition, the contribution to total noise of the individual components, i.e., film, screen, and quantum noise, was studied. The quantities derived from MTF and WS, namely detective quantum efficiency (DQE) and noise equivalent quanta (NEQ), were also investigated in regard to their dose dependency. It can be demonstrated that the MTF of the screens becomes more favorable when the dye content is increased, while noise is not significantly affected. This suggests the use of a mammography screen capable of greater detail recognition, requiring at least double the dose of today's conventional systems with approximately 80 microGy system dose. On the other hand, the manufacture of a screen with about 60% of the dose of the conventional system is possible with very little loss in image quality. For the systems in common use today (80 microGy), quantum noise represents a considerable share of the total noise at low spatial frequencies, whereas in high spatial frequencies, the graininess of the film dominates quantum noise and screen structure. PMID- 1584146 TI - Dual energy x-ray absorptiometry: the effects of beam hardening on bone density measurements. AB - X-ray tubes have superseded radionuclide sources for dual photon absorptiometry of the spine and hip. However, the use of a polyenergetic spectrum is a potential source of error for x-ray absorptiometers since beam hardening may result in a nonlinear measurement scale for bone mineral density (BMD). A quantitative study of the effects of beam hardening on measurements made with a commercial dual energy x-ray scanner has been performed. Bone was represented by layers of aluminum of linearly increasing thickness which were scanned under water thicknesses ranging from 0 to 25 cm to represent different body thicknesses of soft tissue. Beam hardening had two effects on measured BMD: (i) at a constant true BMD, measured BMD varied with water thickness; (ii) at a constant water thickness, the BMD scale was not precisely linear. For conditions appropriate to spine and hip studies (BMD) values in the range 0.7 to 1.4 g/cm2 and body thickness between 15 and 25 cm) the maximum deviation of measured BMD from a linear scale was 0.023 g/cm2, while the root-mean-square deviation (0.01 g/cm2) was comparable to the measurement precision for a spine or femoral neck scan (about 1%). The largest departures from linearity were found to occur at the thinnest water thicknesses for BMD values in the range 0.2 to 0.6 g/cm2. The effect of scale nonlinearity on the results of longitudinal studies was examined: for a spine scan at 20-cm body thickness, measured changes in BMD slightly overestimated the true change and implied an error of 0.15%/year for a measurement of a true rate of loss of 3% year in a postmenopausal woman. PMID- 1584147 TI - Dynamic pulmonary imaging: performance properties of a digital fluoroscopy system. AB - The physical characteristics of dynamic pulmonary imaging with digital fluoroscopy, which differ from those in DSA equipment, have been determined. The spectral distributions and mean energies were calculated and corresponding exposures with varying high voltage and copper filtration (60-100 kVp, 0-2.83 mm Cu) were measured. The utilization of 90-100 kVp with a filter consisting of 1.39 mm Cu and 3 mm Al minimized disturbing skeletal artifacts and reduced the radiation exposure by a factor of approximately 5 in comparison with imaging at 60 kVp without copper filtration. Simultaneously, the measured signal decreased by about 25%. The mean energy of this spectrum exceeded that of 140 kVp chest imaging. The dynamic pulmonary imaging method produces logarithmically transformed x-ray transmittance values linearly related (r = -0.999) to water thickness between 7-10.5 cm, which is equivalent to the normal range of the chest in pediatric patients. A good linear correlation (r = 0.933,N = 92) was obtained when the change in transmitted radiation was compared with tidal volume measured in a rabbit model using a pneumotachometer. The results indicate that the method is applicable for quantitative measurements of pulmonary ventilation. Changes in tidal ventilation can be measured with this noninvasive x-ray imaging technique. PMID- 1584149 TI - Comparative evaluation of image segmentation methods for volume quantitation in SPECT. AB - A wide variety of image segmentation techniques have been proposed for the measurement of organ or lesion volumes in SPECT images. Evaluation of the relative performance of the various methods is difficult due to wide variations in system response characteristics, size, shape, and contrast of the imaged objects, and image acquisition and processing techniques. Selected image segmentation methods for volume quantitation in SPECT were applied to a set of simulated SPECT images containing objects ranging in volume from 1.8 to 113.1 cc. The specific segmentation methods included: (1) operator drawn regions of interest, (2) count-based methods, (3) three levels of fixed thresholds, (4) an adaptive threshold (GLH method), (5) a two-dimensional (2-D) edge detection method, and (6) a three-dimensional (3-D) edge detection method. In general, the 3-D edge detection method required minimal operator intervention while providing the most accurate and consistent estimates of object volume across changes in object contrast and size. PMID- 1584148 TI - Grids or air gaps for scatter reduction in digital radiography: a model calculation. AB - The relative advantages of grids and air gaps for scatter reduction in a digital radiography system were investigated using a theoretical model. In this model the properties of the scatter reduction device are described by primary transmission and selectivity. The signal-to-noise (SNR) improvement factor for fixed exposure to the patient was used as a performance indicator. The results show that the SNR improvement depends strongly on the local scatter fraction; for all practical configurations, however, it stays below a factor of 2. For high scatter fractions, an air gap of 20 cm has about the same effect on SNR improvement as a highly selective grid; for low and medium scatter conditions the air gap performs better than any grid. Additive system noise reduces the SNR improvement factor compared to the case with quantum noise only, the reduction being more pronounced for the grids than for the air gap. The results suggest that the use of an air gap instead of a grid is advantageous in digital radiography systems. PMID- 1584150 TI - Detection nonuniformity measurements and corrections for cone beam transmission CT on a gamma camera. AB - Cone beam transmission CT (CB-CT) improves SPECT imaging by providing high quality attenuation maps for attenuation compensation and for correlated SPECT and CT imaging. The present work measures the detection nonuniformity for CB-CT implemented with a gamma camera, and applies nonuniformity corrections to make CB CT more uniform and accurate. Two cone beam collimators were investigated, as well as the uncollimated cone beam geometry, using both uniformity images and CB CT reconstructions of a uniform circular cylinder. Uniformity images were acquired as a function of point source position relative to the nominal focal point. The uniformity images for both collimators were highly nonuniform, with some regions differing by more than 15% from the average image counts per pixel, indicating that the holes do not focus to the same point. The most uniform images were obtained with the point source located at or near the nominal focal point. Radiographs estimated the misfocusing of the holes to be about 0.6 degrees in some regions. There were no indications that the hole size was nonuniform. The CB CT reconstructions of data acquired with collimator showed no obvious signs of image artifact from the detection nonuniformities. However, low-noise simulated data with well-localized detection defects produced readily-apparent circular artifacts. The nonuniformity correction was accurate and easy to apply, and should be used whenever quantitative accuracy is required. The uniformity images acquired without collimator lacked the collimator-produced nonuniformities, but had decreased counts near the detector edge. The decrease was predictable, using simple geometric considerations. Uniform cylinder reconstructions of "without collimator" data showed a corresponding decrease in center density relative to the edge (edge-to-center ratio = 1.25), which was improved by the nonuniformity correction (ratio = 0.21). Accurate CB-CT without collimator will require further correction for photon scatter. PMID- 1584151 TI - Removing effects of eddy currents in proton MR spectroscopy. AB - The use of pulsed gradients to define a volume of interest for localized magnetic resonance spectroscopy produces magnetic field perturbations which distort both the free induction decay and the spectrum after Fourier transformation. A technique is presented that removes the artifacts from eddy currents from a sampled free induction decay. To linearize the phase, the nonlinear phase of a reference free induction decay is subtracted from the phase of a sample free induction decay. Next, to move the frequency to resonance and perform a zero order phase correction, the line fit from a linear regression is subtracted from the phase. After reconstructing the free induction decay, the resulting frequency spectra are sorted into absorption mode and dispersion mode components. PMID- 1584152 TI - Comments on: "Transfer function measurements and analysis for a magnetic resonance imager," Mohapatra et al. [Med. Phys. 18, 1141-1144 (1991)]. PMID- 1584153 TI - Medicine in the trenches. The agony and the ecstasy of the rural practitioner. PMID- 1584154 TI - TV doctor, Michael Breen. PMID- 1584155 TI - Clinician responsibilities under the National Childhood Vaccine Injury Act. PMID- 1584156 TI - Minnesota HIV/HBV Joint Task Force recommendations. Executive summary. PMID- 1584157 TI - The result of an educational intervention for physicians providing HIV-antibody testing and counseling. AB - Based upon our findings related to physicians' human immunodeficiency virus (HIV) antibody-testing practices in a multispecialty group practice, we randomly selected a group of family practice physicians and over six months provided them with patient education resources and information about HIV-antibody-testing guidelines and their own patient counseling practices. Following this intervention, a chart audit showed that documentation of patient counseling had doubled. We also noted positive, albeit minor, changes in obtaining informed consent. Physicians ordered fewer tests overall; however, we found a slight increase in testing for "inappropriate" reasons. PMID- 1584158 TI - New OSHA rule governs employees' exposure to bloodborne pathogens. PMID- 1584159 TI - Rural health care delivery. Survival may require an integrated model. PMID- 1584160 TI - Physician apathy guarantees exclusion. PMID- 1584161 TI - Mayo's Medicare dollars to drop. PMID- 1584162 TI - AZT research. PMID- 1584163 TI - Physician broadcaster gets good reception. PMID- 1584164 TI - Project 2000 curriculum evaluation: the case for teacher evaluation. AB - Project 2000 has changed the role of nurse teachers. Thus evaluation of Project 2000 should incorporate a theoretical framework that not only evaluates the individual school/college of nursing curriculum but also enhances the teachers' professional development. This paper suggests that teacher professional development would be enhanced by teacher self-evaluation (action research). A collaborative approach between teachers and an evaluation co-ordinator would ensure that the quality of the curriculum is maintained (MacDonald 1991). It is argued that the implementation of monitored innovation would fulfil the criteria for the developing school/college of nursing put forward by Holly et al (1989). PMID- 1584165 TI - Dealing with verbal abuse: evaluation of the efficacy of a workshop for student nurses. AB - Verbal abuse is a problem that can confront all health care professionals in their day to day practice. Studies into abuse of professionals have emphasised the stressful effects of non-physical violence and have shown that it is often the most inexperienced members of various professions who are in the 'front line' of such attacks. The group of staff particularly at risk are student nurses (HSC 1987). This paper presents an evaluative study of a workshop devised to help student nurses to deal with verbal abuse (Wondrak 1989). Psychiatric nursing students were studied from two intakes into a training course. A simulated situation of an interview with a verbally abusive patient was video taped and assessment was made by independent raters of each subjects ability to deal with the situation. 14 of the subjects then attended a verbal abuse workshop and when re-tested, their ability to deal with abuse was compared with those 15 student nurses who did not attend a workshop. The findings are encouraging, indicating that there is a significant change in the experimental group on a number of variables, related to both practical and emotional aspects of dealing with abuse. Thus the efficacy of the short workshop in improving ability to deal with verbal abuse was demonstrated. PMID- 1584166 TI - Learning from incidents of violence in health care. An investigation of 'case reports' as a basis for staff development and organisational change. AB - How can health care staff be helped by learning about aggression and violence in health care settings. This is a report of how 'Case Reports' were used as a basis for staff development through educational intervention and organisational change. The project was carried out in two stages. Firstly, 'Case Reports' were collected to document and illuminate the experiences of health care staff, and these reports were used as a basis for teaching and learning. Secondly, opportunities were provided for health care staff to review existing policies and guidelines relevant to aggression and violence in health care settings. The views of 253 health care staff from five Health Authorities were explored. Health care staff reported 1) experiencing verbal abuse, hostility, actual contact violence, fears and anxieties during work; 2) that although they were exposed to aggression and/or actual contact violence, training was sparse or non-existent; 3) that policies and guidelines where they existed were out of data and were not relevant to the variety of health care settings in which they worked; and 4) that their skills in this area could be improved through training, with particular attention to listening skills, facilitation skills; verbal and non-verbal communication and assertion skills. PMID- 1584167 TI - Evaluation of tools to assess clinical competence. AB - Assessment of student nurses' clinical skills is an important issue in nurse education. However suitable instruments are difficult to locate, and also to design. In the course of this article the need for scientifically designed and tested assessment instruments is discussed. The thoroughness with which 11 clinical assessment documents were developed was evaluated using specific criteria. It was found that in the majority of cases use of a systematic research process to guide development was not evident. However it must be noted that the assessment documents were only evaluated via their presentation in journal articles. Full details of the entire project had perhaps not been published. The implications of the results, some of the difficulties inherent in instrument design and the limitations of this small review are considered. PMID- 1584168 TI - Modularisation--its versatility and value. AB - The issue of credit accumulation is topical and offers real prospects for nursing education to be considered as a part of an academic continuum in keeping with higher education. It cannot easily be considered without taking into account modularisation which offers a structure for the justification and award of credits. Modularisation of courses holds exciting prospects and offers a practical, logical approach to course development. Modules can be versatile and used in very cost-effective and efficient ways, both as an integral part of the course and as free-standing entities. This article considers the building of a curriculum using a modular approach. The terms module, credit and levels are examined to provide full background information. Also identified are some of the additional potential uses of modules. The work is written from the experience of developing modular courses and offers examples from an existing Diploma. There are, however, some notes of caution and these are raised to add balance to the otherwise enthusiastic discussion. PMID- 1584169 TI - Statistics: a painless injection. AB - This paper springs from experience in the teaching of research methodology and statistics to a wide variety of post-registration health professionals attending courses in higher education (Community Psychiatric Nurses, Occupational Health Nurses, Health Visitors etc.). The paper has two main aims: 1. To describe and comment upon the nature of the learning problems perceived by nurses who are required to confront research methodology and/or statistical methods as components of their chosen post-registration course. 2. To describe a teaching approach and a teaching schema which the writer has found to be successful in promoting knowledge, skills, and--above all--confidence in the handling of methodology/statistics related material by such students. PMID- 1584170 TI - Clinical supervision in psychiatric nursing: using the process record. AB - This paper explores the need for more creative supervision in mental health nursing, to meet the challenges of case-load management and the psychotherapeutic approach to care. One method, the process record, is explored in detail and its role in the supervisory relationship is discussed. PMID- 1584171 TI - From novice to expert: the use of intuitive knowledge as a basis for district nurse education. AB - Curriculum development in nursing should be a dynamic process set within a context which unites theory and practice. Nursing is operating within a climate of ubiquitous change and reliance must be placed upon a robust and professionally enhancing curriculum framework. At the University of Liverpool, the recently validated Diploma in District Nursing has been based upon the work of Patricia Benner 'From Novice to Expert' (1984). Benner's proposals are gaining considerable international credence and, whilst acknowledging that North American models are not always readily transferable into practice within the United Kingdom, the author explains why the combination of skills acquisition and clinical expertise provide an exciting framework pertinent to post registration courses such as district nursing. Those limitations of interpretation derived from culture and the institutional settings of the research are identified. The article which follows explains the reasons which underpin the adaptation of Benner's model to the education and practice of district nursing, identifies the advantages and limitations and concludes by describing how the educational change process was managed to support practice. PMID- 1584172 TI - Nurse education in the post-Fordist era. AB - This paper aims to place the current changes impacting on nurse education into the wider context of massive organisational and managerial upheaval, at present affecting the entire welfare state. This innovation and structural change is, however, merely an echo of deeper societal processes and the influence of the technological revolution on the private industrial sector and market economy. Within this frame of reference the implications of current reforms for the future organisational form, and management, of colleges of nursing are considered. Concerns are also expressed as to the tenuous control of the professional curriculum. PMID- 1584173 TI - Teams and team management in nurse education. AB - Nursing traditionally relied upon power-coercive and status-oriented management styles similar to those which have underpinned failing British industry but team work and team management styles underpin the success and excellence of organisations in industry and commerce. The author argues that such team work and team management can create the dynamic 'problem-solving' style required for the management of complex issues such as exist within nurse education today. The author presents an outline of teams, their characteristics and the models currently available for managing, building and maintaining teams. PMID- 1584174 TI - A brief history of parkinsonism. AB - The growth of our knowledge of Parkinson's disease over the past 175 years represents an enormous and at times stormy intellectual voyage. It required the contributions of many scientists and clinicians in many disciplines, and its progress inevitably reflected the general progress of biomedical science over the past 2 centuries. The advances in the past half century clearly depended on the great advances achieved in that time in histochemistry, neurochemistry, and neuropharmacology as well as in clinical neurology and neuropathology. Advances in the future will similarly depend on progress in modern neuroscience. PMID- 1584175 TI - Parkinson disease. PMID- 1584176 TI - Epidemiology of Parkinson's disease. AB - Additional epidemiologic studies may provide important insights into the etiology of Parkinson's disease. Moreover as the elderly population of Europe and the United States grows, accurate public health planning requires accurate incidence and prevalence estimates. The recent development of a therapy that may slow disease progression (see article by Tetrud elsewhere in this issue) makes early identification and treatment of Parkinson's disease particularly important. Investigations of early markers of Parkinson's disease or markers of disease susceptibility are critical areas of future research, requiring careful collaboration between epidemiologists and laboratory scientists. PMID- 1584177 TI - The natural history of Parkinson's disease in the pre-levodopa and post-levodopa eras. AB - Since Parkinson's disease was first described by James Parkinson in 1817, the natural history has been confounded by various treatment modalities: the replenishment of deficient dopamine, the addition of the dopamine agonists, and the more recent addition of drugs whose putative action may slow the natural history of the disease. Nevertheless it remains a disease that is slowly and inexorably progressive over several decades. The quality of life during this progression can be improved, and the duration of life before inanition produces life-threatening complications can be extended. New approaches to identifying the disease before the overt symptoms appear and to slowing the progression of the underlying pathophysiology are being explored but to date have not produced significant changes in the prognosis for the individual patient. PMID- 1584178 TI - Differential diagnosis of Parkinson's disease and the parkinsonism plus syndromes. AB - Although Parkinson's disease (PD) is thought to represent a specific clinical pathologic entity, up to 20% of patients diagnosed as having PD will have another disorder at autopsy. Furthermore, pathologic features typically associated with PD can also be observed in patients with other neurodegenerative disorders. This article attempts to point out the difficulties in differentiating PD from progressive supranuclear palsy and other parkinsonism plus syndromes and various causes of parkinsonism associated with cognitive changes. The clinical and pathologic differentiation of these disorders are discussed. These disorders are usually associated with postsynaptic receptor changes and therefore levodopa and dopamine agonists provide limited benefit. PMID- 1584179 TI - Neuropathology of Parkinson's disease and related syndromes. AB - A progressive parkinsonian disorder predicts pathology in the substantia nigra and possibly elsewhere in the basal ganglia. Parkinson's disease is a manifestation of Lewy body disease, which is characterized by the association between Lewy bodies and cell degeneration in specific neuronal populations. Striatonigral degeneration is part of multiple system atrophy and is characterized by striatal and nigral degeneration without neuronal inclusion bodies, but glial inclusions have been described. Steele-Richardson-Olszewski disease is characterized by the globose neurofibrillary tangle and predominant brain stem pathology. Corticobasal degeneration shows similar midbrain pathology and a round, filamentous inclusion in the substantia nigra, not unlike the globose tangle, but there is also focal frontoparietal cortical atrophy. The combination of the distribution of degeneration and nerve cell morphology identify apparently distinct disorders, but most of the neuronal inclusions are not disease specific. PMID- 1584180 TI - Dopamine receptors in Parkinson's disease. AB - In vitro and in vivo studies of striatal dopamine receptor changes have been reviewed in this article. A background of receptor pharmacology methods has been included to assist the reader in assessing the merits of the published studies. Overall the literature is not consistent in the relevant observations in parkinsonian brains. D2 receptors are increased in the striatum of parkinsonian patients who have not been exposed to L-dopa therapy. This has been confirmed by both in vivo and in vitro experiments. This supersensitivity is reversed with L dopa treatment, but it is unclear as to the time sequence of this reversal and the clinical correlation that this has. D1 receptors have also been shown to be up-regulated in postmortem tissues from nontreated patients. The density seems to be normal compared with controls after treatment is initiated. A single PET study, however, did not find any differences in D1 binding between untreated parkinsonian patients and controls, and we must await further studies before conclusions may be reached. There are a number of new receptor subtypes that were recently identified with molecular biology techniques. Their relevance to Parkinson's disease is currently unknown, and we await reports of potential changes in these sites in this condition. In addition to these new subtypes, there has been tremendous progress in molecular techniques to understand the regulation of receptor protein formation in different brain regions in response to dopaminergic denervation. In the near future, we may encounter reports of changes in receptor regulation that may help us in understanding the changes that occur in Parkinson's disease. PMID- 1584181 TI - What process causes nigral cell death in Parkinson's disease? AB - The action of toxins or the altered metabolism of dopamine may lead to oxidative stress in substantia nigra, thereby inducing dopamine cell death and the onset of Parkinson's disease. Postmortem studies showing a depletion of reduced glutathione and increased mitochondrial superoxide dismutase activity suggest the occurrence of an ongoing toxic process in substantia nigra involving free radical mechanisms. Indeed there is a selective impairment of complex I of the mitochondrial respiratory chain in substantia nigra in Parkinson's disease, mimicking the mode of action of the selective nigral toxin MPTP. The increased formation of free radical species in substantia nigra in patients with Parkinson's disease may be accelerated by an accumulation of iron within this brain region. Altered iron metabolism and impaired mitochondrial function are not apparent in the early stages of the illness and therefore may act as accelerators of some other primary pathologic process. PMID- 1584182 TI - Magnetic resonance imaging in parkinsonism. AB - MRI is a relatively simple, safe, in vivo technique that has proved to be of great value in differentiating patients with Parkinson's disease from those with atypical parkinsonism, and it is the first laboratory marker to be able to do so. By permitting the in vivo detection of increased iron in the nigra and striatum of patients with parkinsonism, MRI may also have provided a clue into the mechanism of cell death in neurodegenerative disorders. Finally it is conceivable that MRI scanning may serve as a screening tool that permits the early recognition of pathologic iron accumulation before the development of clinical symptoms. This is reasonable to anticipate for patients with atypical parkinsonism in whom large quantities of iron appear to accumulate in the putamen early in the disease. It is possible that with some refinement, abnormalities in the nigra may be detected on MRI with a higher level of certainty. In an era in which we may be able to provide neuroprotective therapy, MRI might be an important technique for defining a population of patients at risk for the development of Parkinson's disease who might benefit from presymptomatic therapy. PMID- 1584183 TI - Positron emission tomography studies in parkinsonism. AB - PET imaging is a rapidly expanding technique with growing clinical utility. In this review, we have discussed the contribution of functional neuroimaging with PET in elucidating the pathophysiology of parkinsonism. In addition, we emphasize the growing role of this technique in the clinical setting. FDG/PET has become increasingly available at major medical centers and is especially suitable as an aid in the clinical assessment of patients with akinetic-rigid or other movement disorders. Although this technique is essentially quantitative and ideally suited for broad population studies, qualitative and semiquantitative approaches may suffice in the evaluation of individual patients. To the extent that several of the functional imaging models are linear with raw count rates, blood sampling may not be needed in each instance. Moreover recent advances in SPECT perfusion imaging may permit the extension of PET diagnostic criteria to other imaging modalities that are less costly and more accessible in the community setting. New statistical methods for the detection of regional metabolic covariation patterns hold special promise for the development of disease-specific imaging markers, which may permit rapid differential diagnosis, improved drug trials, and possible preclinical detection. F-dopa/PET has provided many important in vivo insights into the nigrostriatal dopamine system and its role in the development of parkinsonism. In contrast to FDG/PET, this technique demands specialized radiochemistry, plasma analysis, and modeling approaches that currently restrict its applicability to a few research PET centers. Several promising developments in radiochemical synthesis, data acquisition, and kinetic modeling may simplify the technique sufficiently to be used in the clinical domain. F-dopa/PET holds particular promise in preclinical screening of individuals at risk for Parkinson's disease on genetic or environmental grounds. This has great significance in view of the concurrent availability of potentially neuroprotective pharmaceuticals. Similarly this technique has great potential in objectively measuring rates of disease progression in normal and treated populations. We believe that with greater availability, these PET techniques and others currently under development will have significant impact on the diagnosis and management of patients with Parkinson's disease and related disorders. PMID- 1584184 TI - The role of motor cortex in the pathophysiology of voluntary movement deficits associated with parkinsonism. AB - The characteristic motor deficits of parkinsonism result from dysfunction of the nigrostriatal dopaminergic system of the basal ganglia. These subcortical deficits must ultimately be expressed at the cortical and spinal motoneuron levels to result in the difficulty with initiation and execution of movements seen in parkinsonism. This article describes the neuronal activity of two motor cortical regions, the primary motor cortex (MI) and supplementary motor area (SMA), which receive the majority of basal ganglia outputs related to movement control through the ventral lateral thalamus. The kinematics and electromyographic characteristics of stimulus-initiated and self-initiated normal and parkinsonian movements are described, and the possible relation of SMA and MI task-related neuronal activity to the parkinsonian movement deficits is reviewed. PMID- 1584185 TI - Cognitive impairments in Parkinson's disease. AB - The clinical neuropsychologic profiles of patients with Parkinson's disease and patients with SDAT show both overlap and dissociation. Speech, language, and certain memory skills are examples of dissociable differences, especially in the early stages of the disease. Furthermore the presence of depression, evidence of cognitive slowing, and absence of aphasia in patients with Parkinson's disease suggest prominent subcortical involvement. It is probably premature to categorize all of the cognitive changes in patients with Parkinson's disease as subcortical, however. Some skills, such as visuospatial and executive functions, are impaired in both disorders, and although the etiologic bases for task failure may differ for each, this issue remains open-ended. Another problem is that often the evidence for or against the cortical/subcortical distinction is insufficient and in some cases based on a single measure thought to be representative of a given cognitive domain. Most importantly there are few comparative studies that provide unequivocal support for making a cortical/subcortical distinction. Failure to equate for level of cognitive impairment or functional disability between dementias and strict adherence to cross-sectional study designs further compromise efforts to characterize each syndrome precisely. Whitehouse suggested that a prospective study of several different dementias studied in parallel, examining a wide range of cognitive skills, is required before the cortical/subcortical classification scheme can be validated. A critical component is an autopsy program to confirm diagnoses and provide clinicopathologic correlation. It is possible that the diverse nature of the cognitive impairment in patients with Parkinson's disease is not a methodologic artifact but reflects multiple disease subtypes. Ross, Mahler, and Cummings proposed three dementia syndromes in patients with Parkinson's disease: one that is relatively mild and meets the criteria for subcortical dementia, a second that is more severe and shows a wider range of cognitive impairment but is still neuropathologically distinct from SDAT, and a third severe dementia with both subcortical and cortical involvement that may reflect basal ganglia and Alzheimer-type pathology. PMID- 1584186 TI - Levodopa: pharmacology, pharmacokinetics, and pharmacodynamics. AB - The success of L-dopa therapy in patients with Parkinson's disease and the concepts discussed in this article are summarized in Figure 6. Even in advanced stages of disease, 80% of parkinsonian disability remains responsive to L-dopa therapy. The 50% of the response contaminated by response fluctuations should be viewed, at least in part, as a hopeful sign that the system is still responding to L-dopa therapy. Unfortunately suboptimal control of response fluctuations is still a source of consternation for patient and treating physicians alike. Response fluctuations notwithstanding, it should be emphasized that patients actually do better at every stage of disease for having been on L-dopa, as recently confirmed in a retrospective study of the relationship between response fluctuations and the timing of initiation of therapy. To the extent that the increasing frequency, amplitude, and complexity of response fluctuations add to the overall parkinsonian disability, the phenomenon demands a better understanding that will hopefully lead to better corrective or preventive measures. PMID- 1584187 TI - Treatment strategies for extension of levodopa effect. AB - The initial benefits of levodopa decline for as many as half of all patients with Parkinson's disease treated for 2 years or more. Although levodopa is the most effective means for symptom relief, many parkinsonian patients lose the consistency of optimal symptom control. The variability experienced by such patients may arise from several alternative mechanisms at the level of the central nervous system (e.g., a narrowed therapeutic window for receptor-mediated effects or the loss of storage capability for dopamine in the parkinsonian brain). Whatever the cause, several practical methods have been developed. Dopaminergic agonists have played a major role in improving such problem. There are also several strategies for enhancing levodopa's dose by dose effectiveness, including sustained-release levodopa preparations and enteral infusions of levodopa. Another approach is the use of selegiline (deprenyl), MAO-B inhibitor slowing the breakdown of dopamine and thereby extending the duration of levodopa effect. Although selegiline can lessen the abruptness of levodopa wearing off, it can also exacerbate undesired peak effects of the drug. Clinical trials are planned with levodopa pro-drugs and inhibitors of catechol-O-methyltransferase to learn if these approaches can improve problems of long-term levodopa therapy. PMID- 1584188 TI - Protective and preventive therapeutic strategies: monoamine oxidase inhibitors. AB - There is convincing evidence that monotherapy with 10 mg of selegiline daily substantially delays parkinsonian disability, although whether this delay is due to a symptomatic or protective mechanism remains a matter of debate. Evidence against a symptomatic effect is that the wash-out evaluation in two double-blind, placebo-controlled studies failed to detect clinical decline 1 month after discontinuing selegiline. Yet it can be argued that 1 month was not long enough to eliminate the biologic effect of the drug. Thus further studies are required to answer this question definitively. Nonetheless, because selegiline delays the requirement for levodopa therapy and appears to be relatively safe when used as monotherapy, it seems reasonable to recommend this drug as initial treatment when Parkinson's disease is first diagnosed. There is little doubt that future therapeutic and diagnostic strategies for Parkinson's disease and other neurodegenerative diseases will be profoundly influenced if this drug is unequivocally demonstrated to slow progression of Parkinson's disease. Such a finding would be a potent argument for developing biomarkers of preclinical disease because early intervention with such protective therapy might even halt the disease before symptoms develop. PMID- 1584189 TI - Future perfect? Presymptomatic diagnosis, neural transplantation, and trophic factors. AB - Parkinson's disease has served as the prototype for study of degenerative neurologic diseases, perhaps because in patients with Parkinson's disease a set of conspicuous symptoms is due to loss of neurons in a single nucleus, the substantia nigra pars compacta. The restricted pathology enabled researchers to understand the salient biochemical abnormalities of and to develop effective drug therapies for Parkinson's disease. Our understanding of Parkinson's disease may enable identification of markers for presymptomatic diagnosis of the disease. Trophic factors and transplantation enabled researchers to begin to develop and implement strategies to protect remaining dopaminergic neurons in the substantia nigra pars compacta and to restore dopaminergic innervation in the striatum. PMID- 1584190 TI - Compendium of animal rabies control, 1992. National Association of State Public Health Veterinarians, Inc. AB - The purpose of this Compendium is to provide rabies information to veterinarians, public health officials, and others concerned with rabies control. These recommendations serve as the basis for animal rabies control programs throughout the United States and facilitate standardization of procedures among jurisdictions, thereby contributing to an effective national rabies control program. This document is reviewed annually and revised as necessary. Immunization procedure recommendations are contained in Part I; all animal rabies vaccines licensed by the United States Department of Agriculture (USDA) and marketed in the United States are listed in Part II; Part III details the principles of rabies control. PMID- 1584191 TI - World No-Tobacco Day, 1992. AB - The theme of the fifth World No-Tobacco Day, May 31, 1992, is "Tobacco-Free Workplaces: Safer and Healthier." Each year, the objectives of World No-Tobacco Day are to encourage governments, communities, and groups worldwide to become aware of the hazards of tobacco use and to encourage all persons who use tobacco to quit for at least 24 hours. PMID- 1584192 TI - Discomfort from environmental tobacco smoke among employees at worksites with minimal smoking restrictions--United States, 1988. AB - Exposure to environmental tobacco smoke (ETS) is a potential occupational carcinogen according to guidelines of the Occupational Safety and Health Administration (OSHA) carcinogen policy (1). Exposure to ETS in the workplace may represent a substantial contribution to lifetime ETS exposure (2). For many persons, ETS irritates the conjunctiva of the eyes (accompanied by reddening, itching, and increased lacrimation) and the mucous membranes of the nose, throat, and lower respiratory tract (accompanied by itching, coughing, and sore throat) (3). As part of the 1988 National Health Interview Survey-Occupational Health Supplement (NHIS-OHS), CDC measured the degree of discomfort caused by ETS in the workplace. The NHIS-OHS collected information on cigarette smoking, workplace smoking restrictions, and perceived discomfort caused by ETS at the workplace. This report summarizes survey findings and describes efforts to reduce ETS at the workplace. PMID- 1584193 TI - Cigarette smoking among adults--United States, 1990. AB - An essential component of tobacco-control programs is the monitoring of tobacco use over time (1). To determine the prevalence of smoking among adults in the United States during 1990, the National Health Interview Survey-Health Promotion and Disease Prevention (NHIS-HPDP) supplement collected self-reported information about cigarette smoking from a representative sample of the U.S. civilian, noninstitutionalized population. This report presents data from that survey supplement. PMID- 1584194 TI - Cigarette smoking among Chinese, Vietnamese, and Hispanics--California, 1989 1991. AB - Although cigarette smoking causes 434,000 premature deaths annually in the United States (1), information characterizing smoking behaviors generally lacks specificity for racial/ethnic groups and subgroups (2). To characterize smoking and other risk behaviors more fully for program planning efforts at the local level, three California communities and the California Department of Health Services developed culturally adapted versions of CDC's Behavioral Risk Factor Surveillance System (BRFSS). These surveys were administered to selected Chinese (3), Vietnamese (4), or Hispanic populations in California. This report summarizes information about smoking from these surveys during 1989-1991. PMID- 1584195 TI - Outbreak of Salmonella enteritidis infection associated with consumption of raw shell eggs, 1991. AB - Salmonella enteritidis (SE) is the most frequently reported Salmonella serotype in the United States. From January through December 1991, state health departments reported 66 outbreaks of SE in the United States to CDC. This report describes an SE outbreak associated with consumption of raw shell eggs and underscores the necessity of adequately cooking shell eggs. PMID- 1584196 TI - Public health focus: fluoridation of community water systems. AB - Although fluoridation of community water is highly effective in reducing the occurrence of dental caries, the prevalence of dental caries remains high in the United States. For example, a survey of school-aged children during 1986-1987 indicated that 50% of those aged 5-17 years had caries in their permanent teeth, and among 17-year-olds, the prevalence of caries was 84% (1). In addition, among certain populations (e.g., rural and inner-city residents, children whose parents have less than a high school education, and some racial/ethnic minorities), the prevalence of dental caries among children ranges from 52% to 92%. This report summarizes information regarding the efficacy, effectiveness, and cost effectiveness of fluoridation of public water supplies in the United States. PMID- 1584197 TI - HIV seroprevalence among adults treated for cardiac arrest before reaching a medical facility--Seattle, Washington, 1989-1990. AB - As part of an ongoing study of determinants of out-of-hospital cardiac arrest, the Seattle-King County Department of Health conducted an anonymous human immunodeficiency virus (HIV) serosurvey of these patients in Seattle from January 1989 through December 1990. The serum specimens were obtained from patients for whom cardiopulmonary resuscitation (CPR) was initiated by bystanders or emergency medical technicians (EMTs) and for whom endotracheal intubation and intravenous therapy were administered by paramedics. This report summarizes preliminary findings from this survey. PMID- 1584198 TI - Nitrogen dioxide and carbon monoxide intoxication in an indoor ice arena- Wisconsin, 1992. AB - On February 23, 1992, the Wisconsin Department of Health and Social Services (DHSS) was notified that 11 students from two high schools had been treated in two emergency rooms for acute respiratory symptoms (ARS) (i.e., cough, hemoptysis, chest pain, and dyspnea); two students were hospitalized. All of the students had participated in an indoor ice hockey tournament the previous night. PMID- 1584199 TI - Criteria for a recommended standard: occupational exposure to ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, and their acetates. PMID- 1584200 TI - Phosphorylation-induced conformational changes in the phosphorylase ab hybrid as revealed by resolution of pyridoxal 5'-phosphate with imidazole citrate and cysteine. AB - The accessibility of pyridoxal 5'-phosphates of the phosphorylase ab hybrid to resolution by imidazole citrate and cysteine was studied and compared with that of the b and a forms. Promotion of resolution of phosphorylated forms by raising the temperature or in the presence of glycogen indicates that the resistance of phosphorylase a and ab to resolution at 0 degrees C is due rather to their tetrameric state than their phosphorylation-related active conformation. The pattern of resolution of the ab hybrid was similar to that of the a and differed from that of the b forms in that it occurred at 30 degrees C and 37 degrees C but not at 0 degrees C, moreover, it did not show first-order kinetics. On the other hand, inhibition of resolution by ligands binding to the nucleotide site of phosphorylase reflected an intermediate sensitivity of the ab form between that of the b and a forms. We conclude that partial phosphorylation of phosphorylase b elicits conformational change(s) in both subunits which influence the monomer monomer interactions and resolution of pyridoxal 5'-phosphates. Resistance of ab hybrid to monomerizing agents as imidazole citrate, comparable to that of other forms, argues for its stability, ruling out its reshuffling into mixtures of phosphorylase b and a. PMID- 1584201 TI - Abundance and state of phosphorylation of the retinoblastoma susceptibility gene product in human colon cancer. AB - In an effort to understand the possible role of Rb in cellular growth control, we have investigated the abundance and the state of phosphorylation of Rb protein (pRb) in normal and colon tumor cell lines as well as in matched colon tumors, adenomas and adjoining normal colonic mucosa. Resting normal human fibroblast cell lines were found to have only unphosphorylated pRb and phosphorylation of pRb occurred when the cells entered G1-S phase. In general, the colon tumor tissues had at least 1.5-2.0 fold increase in the abundance of pRb and 1.5-2.5 fold increase in the percentage of its phosphorylation as compared to the corresponding normal colonic mucosa. Whereas, the adenomas had similar pRb level and its phosphorylation status as observed in the normal colonic mucosa. The actively growing tumor cell lines had approximately two fold higher total pRb than normal cell lines. Although, the percentage of phosphorylated form in growing tumor cell lines as well as normal cell lines were almost equal, it was still considerably higher than normal colonic mucosa. Moreover, DNA binding assay revealed reduced binding affinity of pRb from colon tumor cell line SW480 as compared to the normal cell line WI38. These results suggest that the abundance of pRb and its phosphorylation level may have a role in the cellular growth control in human colonic epithelium. PMID- 1584202 TI - Glutathione reductase from Saccharomyces cerevisiae undergoes redox interconversion in situ and in vivo. AB - Redox interconversion of glutathione reductase was studied in situ with S. cerevisiae. The enzyme was more sensitive to redox inactivation in 24 hour starved cells than in freshly-grown ones. While 5 microM NADPH or 100 microM NADH caused 50% inactivation in normal cells in 30 min, 0.75 microM NADPH or 50 microM NADH promoted a similar effect in starved cells. GSSG reactivated the enzyme previously inactivated by NADPH, ascertaining that the enzyme was subjected to redox interconversion. Low EDTA concentrations fully protected the enzyme from NADPH inactivation, thus confirming the participation of metals in such a process. Extensive inactivation was obtained in permeabilized cells incubated with glucose-6-phosphate or 6-phosphogluconate, in agreement with the very high specific activities of the corresponding dehydrogenases. Some inactivation was also observed with malate, L-lactate, gluconate or isocitrate in the presence of low NADP+ concentrations. The inactivation of yeast glutathione reductase has also been studied in vivo. The activity decreased to 75% after 2 hours of growth with glucono-delta-lactone as carbon source, while NADPH rose to 144% and NADPH+ fell to 86% of their initial values. Greater changes were observed in the presence of 1.5 microM rotenone: enzymatic activity descended to 23% of the control value, while the NADH/NAD+ and NADPH/NADP+ ratios rose to 171% and 262% of their initial values, respectively. Such results indicate that the lowered redox potential of the pyridine nucleotide pool existing when glucono-delta lactone is oxidized promotes in vivo inactivation of glutathione reductase. PMID- 1584203 TI - Preparation of a soluble 58 kDa-3-hydroxy-3-methylglutaryl CoA reductase from liver microsomes and its inhibition by ethoxysilatrane, a hypocholesterolemic compound. AB - On repeated thawing at room temperature of frozen preparations of heavy microsomes from rat livers, HMGCoA reductase activity was solubilized due to limited proteolysis. This soluble enzyme was partially purified by fractionation with ammonium sulfate and filtration on Sephacryl S-200 column. The active enzyme was coeluted with a major 92 kDa-protein and was identified as a 58 kDa-protein after separation by SDS-PAGE and immunoblotting. Ethoxysilatrane, a hypocholesterolemic compound, which decreased the liver-microsomal activity of HMGCoA reductase on intra-peritonial treatment of animals, showed little effect on the enzyme activity with isolated microsomes or the 50 kDa-soluble enzyme when added in the assay. But it was able to inhibit the activity of the soluble 58 kDa enzyme in a concentration-dependent, reversible manner. Cholesterol and an oxycholesterol were without effect whereas chlorophenoxyisobutyrate and ubiquinone showed small inhibition under these conditions. The extra region that links the active site domain (50 kDa protein) to the membrane, present in the 58 kDa-protein appears to be involved in mediating the inhibition by silatrane. PMID- 1584204 TI - Amino acid metabolism in several tissues of the obese Zucker rat as indicated by the tissue accumulation of alpha-amino[1-14C]isobutyrate. AB - Measurements of the tissue accumulation of alpha-amino[1-14C]isobutyrate [1 14C]AIB in lean (+/?) and obese (fa/fa) Zucker rats showed an augmented tissue/plasma ratio in the liver of the obese animals. In contrast, brown adipose tissue AIB accumulation was lower in the fa/fa animals. In response to a 24 h starvation period AIB accumulation was significantly elevated in the liver and plasma of the lean animals and was unchanged in the liver of the fa/fa animals. The circulating concentration of alanine and branched-chain amino acids was elevated in the fa/fa animals as compared to their lean counterparts. These observations suggest that amino acid uptake is not involved in the impaired muscle development observed in the obese Zucker rat and that the ability of brown adipose tissue for amino acid utilization is decreased in the obese animals suggesting that this may partially explain the impaired thermoregulatory capacity observed in brown adipose tissue of obese Zucker rats. PMID- 1584205 TI - Regulation of the expression of lactate dehydrogenase isozymes in human lymphocytes. AB - Mitogen activation of human peripheral lymphocytes leads to a switch in the isozymes of LDH; resting cells contain low activities of only the B4 and B3A forms, whereas activated cells contain high activities of the A4 and A3B forms. B4 LDH is not altered in activated cells. In this study we show that the appearance of the A subunits occurs concomitantly with a several fold increase in the steady state levels of LDH-A mRNA. Responses in LDH-A mRNA are observed within 12 hrs of activation, and are, thus, associated with the G0/G1 transition or with early G1 (Marjanovic et al. Exp. Cell Res. (1991) 193: 425-431). Maximal expression of LDH-A mRNA requires both phorbol ester and concanavalin A, implying a complex regulatory pathway involving cascade systems activated through both the antigen receptor (TR) and protein kinase C. PMID- 1584206 TI - Serum antioxidant enzyme activity in Parkinson's disease. AB - The activities of superoxide dismutase (SOD; EC 1.15.1.1) and glutathione peroxidase (GSHPx; EC 1.11.1.9), the enzymes that metabolize the superoxide anion and hydrogen peroxide, respectively, were measured in serum from healthy subjects and patients with Parkinson's disease (PD). The activities of SOD and GSHPx in patients with PD were higher than those in normal healthy individuals. These results suggest that the increased activities of these enzymes could be due to oxidative stress in the initial stages of this disease. PMID- 1584207 TI - Magnesium-deficiency elevates circulating levels of inflammatory cytokines and endothelin. AB - We have developed two rodent models of diet-induced magnesium-deficiency in which histologically defined cardiac lesions can be induced within two to three weeks. During the development of these lesions, the magnesium-deficient animals exhibit circulating cytokine levels which are indicative of a generalized inflammatory state. Dramatic elevations of the macrophage-derived cytokines, IL-1, IL-6, and TNF-alpha together with significantly elevated levels of the endothelial cell derived cytokine, endothelin, were detected in the plasma of these animals. We believe that the pathophysiological effects caused by the action of these cytokines may play a role in the promotion of cardiovascular pathology associated with magnesium deficiency. PMID- 1584208 TI - Chymotrypsin-reactive antibodies in insulin-dependent diabetes mellitus. AB - In a previous study (Frazier et al., 1990), it was demonstrated that two patients with type 1 (insulin-dependent) diabetes mellitus had antibodies in their serum which reacted with four 29 kDa pancreas-specific proteins on two-dimensional immunoblots. This paper reports on the purification and identification of these pancreatic proteins. The protein with the pI closest to pH7 was purified through the use of ammonium sulfate fractionation and ion-exchange chromatography. Gel filtration chromatography established that the protein's molecular weight was closer to 25 kDa. Amino acid composition and sequence analyses demonstrated homology between the protein and chymotrypsin. It is suggested that an abnormal regulation of chymotrypsin activity might be related to antibodies formed in some diabetic patients. PMID- 1584210 TI - Expression of the glucose transporter isoform GLUT 4 is insufficient to confer insulin-regulatable hexose uptake to cultured muscle cells. AB - Glucose transporter isoform expression was studied in the skeletal muscle-like cell line, C2C12. Northern and Western blot analysis showed that the insulin responsive muscle/fat glucose transporter isoform, GLUT 4, was expressed in these cells at very low levels, whereas the erythrocyte isoform, GLUT 1, was expressed at readily detectable levels. Insulin did not stimulate glucose transport in this cultured muscle cell line. The C2C12 cells were then transfected separately with either GLUT 1 or GLUT 4, and stable cell lines expressing high levels of mRNA and protein were isolated. GLUT 1-transfected cells exhibited a 3-fold increase in the amount of the GLUT 1 transporter protein which was accompanied by a 2- to 3 fold increase in the glucose uptake rate. However, despite at least a 10-fold increase in GLUT 4 mRNA and protein detected after GLUT 4 cDNA transfection, the glucose uptake of these cells was unchanged and remained insulin-insensitive. By laser confocal immunofluorescence imaging, it was established that the transfected GLUT 4 protein was localized almost entirely in cytoplasmic compartments. In contrast, the GLUT 1 isoform was detected both at the plasma membrane as well as in intracellular compartments. These results suggest that acute insulin stimulation of glucose transport is not solely dependent on the presence of the insulin receptor and the GLUT 4 protein, and that the presence of some additional protein(s) must be required. PMID- 1584209 TI - Conversion of human interferon-beta from a secreted to a phosphatidylinositol anchored protein by fusion of a 17 amino acid sequence to its carboxyl terminus. AB - A number of cell-surface proteins are anchored in plasma membranes by a glycosylated phosphatidylinositol (PI) moiety that is covalently attached to the carboxyl-terminal amino acid of the mature protein. We have previously reported the construction of a cDNA clone of a truncated Platelet-derived growth factor (PDGF) receptor that consists of the extracellular domain without the transmembrane and cytoplasmic domains. In the construction of the vector, a sequence of 51 base pairs (bp) from the 3'-untranslated region of the receptor cDNA was linked in frame with the external domain coding sequence. The truncated receptor protein with the peptide VTSGHCHEERVDRHDGE fused to its carboxyl terminus was covalently attached to the membrane by a PI linkage and it was released by phosphatidylinositol specific-phospholipase C (PI-PLC). When the 51 bp sequence was deleted, the external domain receptor protein was secreted into the media. To determine whether the PI linkage of the protein was due to the 17 amino acids added, the peptide was fused to the carboxyl terminus of the secreted protein human Interferon-beta (hu-IFN-beta). Chinese hamster ovary (CHO) cells transfected with the hu-IFN-beta cDNA secreted the protein to the conditioned media, whereas CHO cells transfected with the carboxyl terminus modified-hu-IFN beta cDNA did not secrete detectable levels of protein. CHO cells expressing the carboxyl terminus modified-hu-IFN-beta were treated with PI-PLC, the media and cell lysates were analyzed by SDS-PAGE after immunoprecipitation with antibodies against hy-IFN-beta. The modified protein is anchored to the plasma membrane by a PI linkage and it is specifically released by PI-PLC, whereas a control preparation of CHO cells expressing wild type hu-IFN-beta does not show the same pattern. The 17 amino acid peptide fused to the carboxyl terminus of IFN-beta directs attachment of a PI anchor and targets the fusion protein to the plasma membrane. PMID- 1584211 TI - The role of estrogen response elements in expression of the Xenopus laevis vitellogenin B1 gene. AB - We have used site-directed mutagenesis and a homologous transient transfection system to investigate the role of the two imperfect estrogen response elements (EREs) located at -302/-334 in the 5'-flanking region of the estrogen-regulated Xenopus laevis vitellogenin B1 gene. Deletion of either ERE effectively abolishes estrogen-dependent transcription of the vitellogenin promoter. Neither replacement of the two imperfect EREs with a single consensus ERE at -334, nor insertion of one or two consensus EREs at -359, restores full estrogen responsiveness to the mutant promoter. In competition gel mobility shift assays using the DNA binding domain of the Xenopus estrogen receptor, the consensus ERE was a severalfold more effective competitor than the two imperfect B1 EREs. These data suggest that flanking DNA sequences may exert a significant effect on the activity of EREs as hormone-dependent transcription activators. When the imperfect EREs at -302/-334 were present, an additional consensus ERE at -359 exhibited synergistic activation of transcription. However, two consensus EREs located close to the TATA box showed additive, not synergistic, activation of transcription. In contrast, synergistic activation of transcription was observed in synthetic promoters containing two EREs and either the vitellogenin activator element or the NF1 or AP1 upstream activator elements. PMID- 1584212 TI - Estrogen response module of the mouse lactoferrin gene contains overlapping chicken ovalbumin upstream promoter transcription factor and estrogen receptor binding elements. AB - Transcription of the lactoferrin gene is stimulated by estrogen in mouse uterus. To study direct estrogen regulation of this gene at the molecular level, we cloned and analyzed the 5'-flanking region of the mouse lactoferrin gene. Sequence analysis revealed a putative estrogen-responsive element (ERE) overlapping with a chicken ovalbumin up-stream promoter (COUP) element located at position -349 to -329 from the transcription initiation site. The ERE element differed from the consensus ERE sequence by one nucleotide at the second position of the 3' half of the element (G to A); the COUP element differed by one nucleotide from the chicken COUP element. Synthetic oligonucleotide containing the mouse lactoferrin COUP/ERE element was inserted into the reporter chloramphenicol acetyltransferase vector, then transiently transfected into human endometrium carcinoma RL95-2 cells to assess hormone responsiveness. We found that the COUP/ERE element confers estrogen action to both homologous and heterologous promoters. Nuclear proteins from diethylstilbestrol-treated mouse uteri and proteins from estrogen receptor expression vector-transfected RL95-2 whole cell extract bound in vitro to COUP/ERE element specifically, as assessed by band-shift assay. By using antibodies specific to the estrogen receptor and the COUP transcription factor, we demonstrated that both proteins were present in mouse uterine tissue and interacted specifically with the COUP/ERE element, as shown by the superband shift. Competition experiments with specific ERE or COUP oligonucleotides also confirmed the interaction between lactoferrin COUP/ERE element with the estrogen receptor and the COUP transcription factor. Therefore, we named this sequence mERM, the mouse lactoferrin estrogen response module. PMID- 1584213 TI - Cooperative regulation of cell proliferation by calcium and calmodulin in Aspergillus nidulans. AB - Calcium and calmodulin have been widely implicated in the control of cell proliferation. We have created a strain of the genetically tractable filamentous fungus, Aspergillus nidulans, that is conditional for calmodulin expression. This was accomplished by replacing the unique endogenous calmodulin gene with one regulated by the inducible alcohol dehydrogenase (alcA) gene promoter by homologous recombination. This strain cannot grow when the cells are incubated in medium containing a carbon source that represses the alcA promoter. Characterization of the arrested cells shows that 83% are blocked in the G2 phase of the cell cycle. The block is due to very low levels of calmodulin and is fully reversible upon changing to medium that contains an inducer of the alcA promoter. The rate of cell proliferation in this strain is dependent upon both the intracellular calmodulin and extracellular Ca2+ concentrations. Raising the calmodulin concentration by inducing the alcA promoter not only causes the cells to enter the proliferative cycle more quickly and to grow faster, but also decreases the concentration of extracellular Ca2+ required to support growth by 10-fold, as compared with cells grown in noninducing medium. Thus both the intracellular calmodulin and extracellular Ca2+ concentrations are important and interactive factors in regulating the nuclear division cycle of Aspergillus nidulans. PMID- 1584214 TI - Molecular cloning and expression of the cDNA for a novel A2-adenosine receptor subtype. AB - A novel adenosine receptor subtype has been cloned from a rat brain cDNA library using a probe generated by the polymerase chain reaction. The cDNA, designated RFL9, encodes a protein of 332 amino acids. The structure of RFL9 is most similar to that of the recently cloned rat A2-adenosine receptor, with a sequence identity of 73% within the presumed seven transmembrane domains. Expression of RFL9 in COS-6M cells resulted in ligand binding and functional activity characteristics of an adenosine receptor that is coupled positively to adenylyl cyclase. Examination of the tissue distribution of RFL9 mRNA by Northern blot analysis showed a restricted distribution with highest levels expressed in large intestine, cecum, and urinary bladder; this pattern was distinct from that of either the A1- or A2-adenosine receptor mRNAs. In situ hybridization studies of RFL9 mRNA showed no specific hybridization pattern in brain, but a hybridization signal was readily observed in the hypophyseal pars tuberalis. Thus, RFL9 encodes a novel A2-adenosine receptor subtype. PMID- 1584215 TI - Studies on the role of amino acids 38-45 in the expression of a functional thyrotropin receptor. AB - We previously reported that deletion or substitution of a unique eight-amino acid tract (residues 38-45) in the extracellular domain of the human TSH receptor led to the loss of specific ligand binding to the surface of transfected cells. In the present study we analyzed this region in more detail. Using site-directed mutagenesis of the TSH receptor cDNA, we substituted amino acid residues 38-45, either in three overlapping groups of four amino acids each or individually. The resultant TSH receptor mutant cDNAs were stably transfected into Chinese hamster ovary cells, and the cells were tested for their TSH-binding ability. Our data demonstrate that amino acid residues 38-40 and 42-45 in this region of the human TSH receptor can be substituted without alteration in receptor function and are, therefore, not critical in forming or maintaining the TSH-binding site. However, substitution of Cys41, either alone or together with adjacent amino acids, leads to the loss of TSH binding to its receptor. These data suggest a central role for the amino acid in position 41 in preserving the biological function of the TSH receptor. PMID- 1584216 TI - Regulation of proenkephalin expression in cultured skin mesenchymal cells. AB - Proenkephalin, a classically defined opioid encoding gene, is transiently expressed in nondifferentiated mesodermal cells during organogenesis. We examined the hypothesis that this expression is associated with mesenchymal cell proliferation. For this purpose, we established a cell culture derived from fetal skin mesenchyme that specifically expresses proenkephalin mRNA in correlation with hypodermis development. These mesenchymal cells also produce and secrete significant amounts of proenkephalin-derived peptides. Using this model system, we observed a marked increase in proenkephalin mRNA expression in response to serum. This effect is time dependent and reaches peak levels during the G1/S transition. Similarly, 12-O-tetradecanoyl-phorbol-13-ester, whose biological actions have been shown to be mediated by the activity of protein kinase C (PKC), up-regulates proenkephalin expression. Desensitization of PKC by prolonged exposure of cells to 12-O-tetradecanoyl-phorbol-13-ester attenuates the serum induction of proenkephalin. The results presented in this report demonstrate that proenkephalin expression in mesenchymal cells is regulated by serum factors via mechanisms that involve PKC activity. A possible association between proenkephalin expression and cell proliferation is suggested. PMID- 1584217 TI - Modulation of transcription factor activity by a distant steroid modulatory element. AB - Variations in the biological activity of antisteroids, as determined by their percent agonist activity, is a well known but poorly understood phenomenon. For example, in tyrosine aminotransferase (TAT) induction by the antiglucocorticoid dexamethasone 21-mesylate in rat hepatoma tissue culture cells, the percent agonist activity varies with the density of cultured cells. A 21-basepair sequence of the rat TAT gene has now been isolated which confers all of the induction properties of the endogenous TAT gene to homologous and heterologous promoters and genes. We call this 21-basepair sequence, which acts in concert with a trans-acting factor identified by gel shift experiments, a glucocorticoid modulatory element. The changes in induction properties were found to be independent of the fold induction by dexamethasone, thus arguing that the GME does not synergize with the glucocorticoid response element. A model incorporating this new element is advanced which can explain the observed variations of TAT induction and may be generally applicable for the mechanism of action of other steroid hormones. PMID- 1584218 TI - An additional carbohydrate chain in the variant thyroxine-binding globulin-Gary (TBGAsn-96) impairs its secretion. AB - The T4-binding globulin-Gary (TBG-G) variant has severely impaired T4 binding, is unstable at 37 C, and presents an apparent anodal shift of all isoforms when submitted to isoelectric focusing. Inheritance of this abnormal TBG produces a profound decrease in the serum levels of native TBG with reciprocal changes in its denatured form, causing thyroid hormone concentrations to be as low as those found in complete TBG deficiency. The TBG-G gene possesses a single nucleotide substitution replacing the normal IIe96 (ATC) with Asn (AAC), thus creating a new site for N-linked glycosylation. In order to determine whether TBG-G contains an additional carbohydrate chain as indirectly suggested by the isoelectric focusing results, cDNAs containing the normal TBG (TBG-N), and TBG-G were inserted in the appropriate vectors to allow their expression in mammalian cells (COS-1) and in amphibian (Xenopus) oocytes. In both systems, expression of TBG-G yielded a larger molecule than TBG-N when analyzed by polyacrylamide gel electrophoresis under denaturing conditions. However, both were identical in size when synthesized in COS-1 cells in the presence of tunicamycin or when deglycosylated after their synthesis in Xenopus oocytes. Pulse chase experiments revealed impaired secretion and excessive overall intracellular degradation of TBG-G relative to TBG-N. As expected from studies on serum from affected subjects, in vitro expressed TBG-G had a 10-fold lower affinity for T4. These studies prove that the new site for potential glycosylation created by the point mutation in TBG-G is indeed glycosylated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584219 TI - Local chromatin changes accompany the expression of the calbindin-D28K gene: tissue specificity and effect of vitamin D activation. AB - The high affinity calcium-binding protein calbindin-D28K is one of the known proteins transcriptionally up-regulated by the hormonally active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. This regulation is tissue specific, since in the absence of 1,25-(OH)2D3, the expression of calbindin-D28K is virtually abolished in intestine, whereas it is decreased, but clearly detectable, in kidney, and it remains present at its highest level in cerebellum. Several studies have shown that there is a strong correlation between an increase in the sensitivity to nuclease digestion of a given gene locus and its potential for transcription. Furthermore, hypersensitive sites have often been mapped to regions of DNA including or surrounding sequences known to be important for the regulation of gene transcription. In this study we have scanned the 5'-end and flanking DNA of the calbindin-D28K gene for the presence of DNase-I hypersensitive (DH) sites in order to localize possible regulatory regions involved in the tissue-specific and hormone-dependent regulation of this gene. We have found that in tissues where calbindin is not expressed, such as liver, no DH sites could be detected. In cerebellum, the same set of DH sites was observed in the presence or absence of 1,25-(OH)2D3 treatment, reflecting the vitamin D independent expression of the calbindin gene in this tissue. A more complex pattern of DH sites was found in intestine, independently of the vitamin D status of the animal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584220 TI - Capacity for cooperative binding of thyroid hormone (T3) receptor dimers defines wild type T3 response elements. AB - Thyroid hormone response elements (T3REs) have been identified in a variety of promoters including those directing expression of rat GH (rGH), alpha-myosin heavy chain (rMHC), and malic enzyme (rME). A detailed biochemical and genetic analysis of the rGH element has shown that it consists of three hexamers related to the consensus [(A/G)GGT(C/A)A]. We have extended this analysis to the rMHC and rME elements. Binding of highly purified thyroid hormone receptor (T3R) to T3REs was determined using the gel shift assay, and thyroid hormone (T3) induction was measured in transient tranfections. We show that the wild type version of each of the three elements binds T3R dimers cooperatively. Mutational analysis of the rMHC and rME elements identified domains important for binding T3R dimers and allowed a direct determination of the relationship between T3R binding and function. In each element two hexamers are required for dimer binding, and mutations that interfere with dimer formation significantly reduce T3 induction. Similar to the rGH element, the rMHC T3RE contains three hexameric domains arranged as a direct repeat followed by an inverted copy, although the third domain is weaker than in rGH. All three are required for full function and T3R binding. The rME T3RE is a two-hexamer direct repeat T3RE, which also binds T3R monomer and dimer. Across a series of mutant elements, there was a strong correlation between dimer binding in vitro and function in vivo for rMHC (r = 0.99, P less than 0.01) and rME (r = 0.67, P less than 0.05) T3REs. Our results demonstrate a similar pattern of T3R dimer binding to a diverse array of hexameric sequences and arrangements in three wild type T3REs. Addition of nuclear protein enhanced T3R binding but did not alter the specificity of binding to wild type or mutant elements. Binding of purified T3R to T3REs was highly correlated with function, both with and without the addition of nuclear protein. T3R dimer formation is the common feature which defines the capacity of these elements to confer T3 induction. PMID- 1584221 TI - The estrogenic and antiestrogenic properties of tamoxifen in GH4C1 pituitary tumor cells are gene specific. AB - We have examined the effects of the antiestrogen tamoxifen (TAM) and the estrogen 17 beta-estradiol (E2) on several estrogen-regulated responses in GH4C1 pituitary tumor cells. After 5 days of treatment with either TAM (1.0 microM) or E2 (1.0 nM), the level of PRL mRNA was markedly increased when measured by the cytosolic dot blot procedure. In contrast, only E2 was able to increase the levels of beta actin mRNA and cytosolic protein, suggesting that this estrogen may stimulate cell proliferation over the course of treatment. This apparent difference in the abilities of TAM and E2 to stimulate GH4C1 cell proliferation was examined directly. TAM had no effect on cell proliferation as evidenced by its inability to increase cellular DNA or deoxythymidine triphosphate incorporation by nuclei isolated from treated cells. In contrast, E2 stimulated cell proliferation as evidenced by increases in cellular DNA and deoxythymidine triphosphate incorporation by isolated nuclei. The abilities of TAM and E2 to induce progesterone receptor (PR) and PR mRNA were also examined. TAM was unable to increase the levels of PR or PR mRNA, whereas E2 was effective in both of these regards. When added in combination with E2, TAM acted as a classical antiestrogen, partially blocking the induction of PR by E2. To determine whether the inabilities of TAM to stimulate cell proliferation and induce PR were a function of TAM concentration, dose-response experiments were performed. TAM at concentrations ranging from 10(-8)-10(-6) M was effective in inducing PRL mRNA, but at none of the tested concentrations was TAM effective in stimulating cell proliferation or inducing PR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584222 TI - Analysis of functional cooperativity between individual transcription-stimulating elements in the proximal region of the rat prolactin gene. AB - The proximal region of the rat PRL gene contains at least five transcription stimulating elements that are located within a 170-basepair region up-stream of the TATA box. These cis-acting elements include four binding sites for the pituitary-specific transcription factor Pit-1 as well as another site for an unidentified factor. In this study interactions between different DNA elements have been examined through the construction of PRL-luciferase fusion genes containing mutations that disrupt various combinations of the individual DNA elements. In general, the disruption of multiple factor-binding sites had a much more than additive effect on expression of the luciferase constructs. Interestingly, comparison of the effects of disrupting pairs of binding sites demonstrated substantial differences in the effects of different combinations of mutations, suggesting that cooperative interactions may reflect specific interactions. Mutations that disrupted all five cis-elements of the PRL proximal region essentially abolished transcription from the proximal promoter. This finding suggests that there are no other DNA elements within the proximal 200 basepairs of the PRL gene that can independently stimulate transcription. Although there is strong functional cooperativity between different cis-elements in the PRL gene, DNase footprint studies failed to detect cooperative binding between different Pit-1 elements. Overall, the findings demonstrate that the normal transcription of the PRL gene involves strong cooperative interactions between individual DNA elements in the proximal region. PMID- 1584223 TI - Conversion of bovine growth hormone cysteine residues to serine affects secretion by cultured cells and growth rates in transgenic mice. AB - GHs have been found to possess two disulfide bonds. We set out to determine the importance of bovine (b) GH's disulfide bonds relative to the ability of the hormone to be secreted by cultured cells in vitro and to promote growth in transgenic mice. We have generated six mutated bGH genes that encode serine (Ser) substitutions for cysteines (Cys). These mutated genes were used to generate bGH analogs in which either one or both disulfide bonds are destroyed. When the small loop of bGH was destroyed (Cys181-Ser or Cys189-Ser), the bGH analogs were found to be secreted by mouse L-cells at levels comparable to those of wild-type bGH. However, secretion was drastically reduced when the large loop was abolished (Cys53-Ser or Cys164-Ser). An immunofluorescence study of these bGH analogs revealed two distinct patterns of subcellular localization. Bovine GH analogs with mutations in the small loop demonstrated a perinuclear distribution similar to that of wild-type bGH, but analogs containing a disrupted large loop revealed a uniform cytoplasmic distribution pattern. When these mutated bGH genes were individually introduced into transgenic mice, only those animals that expressed bGH analogs with the large loop intact demonstrated a growth-enhanced phenotype. Transgenic mice that expressed bGH analogs lacking the large loop showed growth rates similar to those of nontransgenic mice. These results suggest that the integrity of the large loop, but not that of the small loop, is essential for the growth-enhancing activity of bGH in transgenic mice. PMID- 1584224 TI - Intrasteric regulation of myosin light chain kinase: the pseudosubstrate prototope binds to the active site. AB - We previously proposed a molecular mechanism for the activation of smooth muscle myosin light chain kinase (smMLCK) by calmodulin (CaM). According to this model, smMLCK is autoinhibited in the absence of Ca2+/CaM due to the interaction of a pseudosubstrate prototope, contained within the CaM binding/regulatory region, with the active site of the enzyme. Binding of Ca2+/CaM releases the autoinhibition and allows access of the protein substrate to the active site of the enzyme, resulting in phosphorylation of the myosin light chains. We now provide direct experimental evidence that the pseudosubstrate prototope can associate with the active site. We constructed a smMLCK mutant in which the five amino acid phosphorylation site of the myosin light chain substrate was inserted into the pseudosubstrate sequence of the CaM binding domain without disrupting the ability of the enzyme to bind Ca2+/CaM. We demonstrate that this mutant undergoes intramolecular autophosphorylation at the appropriate inserted serine residue in the absence of CaM and that this autophosphorylation activates the enzyme. Binding of Ca2+/CaM to the mutant enzyme stimulated myosin light chain substrate phosphorylation but strongly inhibited autophosphorylation, presumably by removing the pseudosubstrate from the active site. These results confirm that the pseudosubstrate sequence has access to the catalytic site and that the activation of the enzyme is accompanied by its removal from this position due to Ca2+/CaM binding as predicted by the model. PMID- 1584225 TI - A nuclear protein is required for thyroid hormone receptor binding to an inhibitory half-site in the epidermal growth factor receptor promoter. AB - The epidermal growth factor (EGF) receptor (EGFR) promoter is negatively regulated by thyroid hormone and retinoic acid. This regulation can be mapped to a 36-basepair GC-rich region of the promoter (EGFR P/E) that functions autonomously as a promoter and an enhancer when placed in front of the thymidine kinase gene TATA element. Direct high affinity binding of the thyroid hormone receptor (T3R) to this element requires a nuclear protein. Through ion exchange chromatography and gel filtration of HeLa nuclear extract, this activity was identified as a protein of approximately 67 kilodaltons. This protein did not bind to DNA alone, but greatly augmented T3R binding to the EGFR P/E sequence in gel mobility shift and DNA precipitation assays. When combined with the T3R auxillary protein (TRAP), the T3R migrated as a larger complex on the DNA. Chemical cross-linking identified this complex as a heterodimer between T3R and TRAP. T3R-TRAP binds to a 7-basepair site in the EGFR P/E (GGGACTC) that has weak homology to a consensus thyroid response element half-site. Thus, on this element, T3R-TRAP heterodimers contact the DNA primarily on a single site that comprises an inhibitory thyroid response element. PMID- 1584226 TI - Retinoic acid stimulates transcriptional activity from the alkaline phosphatase promoter in the immortalized rat calvarial cell line, RCT-1. AB - The immortalized rat calvarial bone cell line RCT-1 responds to treatment with retinoic acid (RA) by increased expression of osteoblast phenotype-related features, including the induction of liver/bone/kidney alkaline phosphatase (ALP) activity. ALP mRNA could not be demonstrated in unstimulated cells, but was first detected in cells treated for 6 h with 1 microM RA. Cycloheximide failed to block the RA induction of ALP mRNA, indicating that de novo protein synthesis was not a requirement for the RA effect and that the ALP gene may be a direct target for RA action. This was confirmed by nuclear run-on assays, which demonstrated a 2.5 fold increase in the abundance of ALP transcripts after 6 h of RA treatment. To determine whether the RA responsiveness was mediated by a specific segment of the ALP promoter, RCT-1 cells were transfected with a series of plasmids containing deletions of the 5'-flanking sequence of the human ALP gene fused to the chloramphenicol acetyl transferase (CAT) gene. CAT activity was measured in cells cultured in the presence of RA or vehicle. All but the smallest construct, which contained 44 basepairs up-stream of the initiation of transcription, were found to mediate a 2- to 3-fold increase in the expression of CAT activity in response to RA. Furthermore, when the region -108 to -45 of the human ALP gene was inserted into the expression vector pBLcat2, in a position immediately up-stream of the herpes simplex virus thymidine kinase promoter, the construct was found to mediate a 2-fold enhancement of CAT activity in response to RA. In gel retardation assays, a major band was present corresponding to the formation of a complex between the 32P-labeled probe containing the -108 to -45 sequence and proteins present in nuclear extracts of RCT-1 cells stimulated for 3 h with RA. These data suggest that the sequence of 64 basepairs (-108 to -45) 5' to the transcription start site is involved in the RA inducibility of the human ALP gene. PMID- 1584227 TI - Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor. AB - The rat GH (rGH) gene is expressed in the pituitary in a highly tissue-specific manner. A pituitary-specific transcription factor, Pit-1 (or GHF-1), and other, more tissue-general factors, including the thyroid hormone receptor (T3R), are important for regulating rGH promoter activity. The relative roles of Pit-1, T3R, and protein kinases in the activation of the rGH promoter were studied. Each component was supplied individually or in combination with the others to human monocyte U937 cells. The transfected rGH promoter was inactive in these cells even when it was cotransfected with either Pit-1 or T3R expression vectors. The rGH promoter carried in a truncated pUC vector could be activated by expression of the T3R if the cells were cultured with inducers of protein kinase-A (forskolin) and protein kinase-C [phorbol 12-myristate 13-acetate (PMA)] activity. By contrast, the PMA- and forskolin-dependent activation of the rGH promoter by Pit-1 expression was comparatively insignificant unless 1) the sequences deleted from the pUC vector (including a putative site for the transcription factor AP1) were restored to the plasmid carrying the rGH promoter; or 2) the T3R was coexpressed, which led to a marked synergistic response. These results indicate the relative inactivity of Pit-1 in isolation from other factors. Activation by forskolin and PMA did not require de novo protein synthesis. The synergistic activation by Pit-1 and the T3R was enhanced, but was not dependent upon, thyroid hormone (T3). The T3-dependent effect operated predominately through a thyroid hormone response element located up-stream of the two Pit-1-binding sites within the rGH promoter, whereas the T3-independent effect did not require any of the known T3R-binding sites on the rGH promoter. These results suggest a role for the more tissue-general T3R and protein kinases in the activation of the rGH promoter. They demonstrate the synergistic interplay between the T3R and Pit-1, underscore the dependence of Pit-1 action on other transcription factors, and implicate Pit-1 as a cofactor, rather than the dominant factor, influencing the tissue-specific expression of the rGH promoter. PMID- 1584228 TI - Measurement of affinity of viral monoclonal antibodies using Fab'-peroxidase conjugate. Influence of antibody concentration on apparent affinity. AB - The binding affinity of a monoclonal antibody to tobacco mosaic virus (TMV) was studied using a Fab'-peroxidase conjugate. Measurement of the enzymatic activity allowed the determination of the amount of free antibody present after ultracentrifugation of virus-antibody complexes at equilibrium. The method was very sensitive and allowed measurements over a 1000-fold range of antibody concns. The calculated affinity constant decreased about 25 fold when the antibody concn used in the binding assay was increased from 30 ng/ml to 35 micrograms/ml. PMID- 1584229 TI - Immunogenicity of Z-DNA depends on the size of polynucleotide presented in complexes with methylated BSA. AB - The importance of polynucleotide size for immunogenicity was tested with size fractionated Z-DNA. High molecular weight Z-DNA, larger than 1000 bp, was fragmented by digestion with micrococcal nuclease. Fractions corresponding to less than 60, 60-120, 100-200, 200-400 and 400-900 bp were isolated by gel filtration on Sepharose 4B. These fractions and the greater than 1000 bp Z-DNA were mixed with methylated BSA and the complexes were injected into C57BL/6 mice with RIBI adjuvant. Only one of four mice responded to the less than 60 bp immunogen. All the fractions larger than 60 bp induced specific anti-Z-DNA antibodies, mostly of IgG isotype, in all animals injected. Fractions larger than 200 bp induced antisera of higher titer than did 60-120 or 100-200 bp fractions. All positive sera reacted with Z-DNA but not with B-DNA and only very weakly with denatured DNA. In competitive assays, similar concentrations of fragments larger than 60 bp inhibited binding to immobilized Z-DNA. A higher concentration of less than 60 bp fragments was required for competitive binding. Even for a highly immunogenic nucleic acid that differs from the B-DNA conformation, a polynucleotide larger than 100 bp is much more immunogenic than smaller fragments. PMID- 1584230 TI - Egr-1 mRNA expression is independent of regulatory proliferative responses in the immature B cell line WEHI-231. AB - We have recently reported cellular growth arrest induced following crosslinking of surface IgM (sIgM) but not surface IgD (sIgD) in the WEHI-231 cell line, representative of the immature B cell stage, and its delta heavy chain (delta) transfectant. An initial report has indicated WEHI-231.7, a subclone of WEHI-231, failed to express Egr-1 mRNA following sIgM crosslinking, in contrast to significant up-regulation found in mature B lymphocytes. The implication for linkage between selective surface immunoglobulin (sIg) signal transduction, expression of immediate/early genes and control of cellular growth imposes an attractive model for induction of immature B cell tolerance. Our investigations examined the relationships between Egr-1 mRNA expression and growth regulation in WEHI-231, WEHI-231.7 and their respective delta-transfectants (WEHI-delta, WEHI delta 7). We report sIgM and sIgD crosslinking leads to a rapid increase of Egr-1 mRNA expression in WEHI-231 and WEHI-delta but not in the subclone WEHI-231.7 and WEHI-delta 7. Nevertheless, both WEHI-231, WEHI-231.7 and their delta transfectants demonstrate the ability to induce growth arrest following sIgM but not sIgD crosslinking. Furthermore, we found Egr-1 expression could be achieved by direct activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) circumventing the classical sIg activated phosphatidylinositol signal transduction pathway. Our results suggest Egr-1 expression does not directly participate in growth regulation of immature B cell clones but rather is a consequence of signal transduction through sIg. PMID- 1584231 TI - Antibody responses to ganglio-series gangliosides in different strains of inbred mice. AB - We studied antibody responses after immunization with ganglio-series gangliosides against 10 strains of inbred mice, including Balb/c, C57BL/6, A/J, C3H/HeN, C3H/HeJ, CBA/N, AKR/N, NZB/N, DBA/2 and nu/nu Balb/c. Twelve gangliosides having NeuAc as their sialic acid moiety (GM4, GM3, GM2, GM1, GD3, O-Ac-GD3, GD2, GD1a, GD1b, GT1a, GT1b and GQ1b), four gangliosides having NeuGc (GM3, GM2, GM1 and GD3) and four asialo-gangliosides (GA4, GA3, GA2 and GA1) were injected intravenously adsorbed to Salmonella minnesota. The antibody titers of the mice sera were determined by an enzyme-linked immunosorbent assay and an immune adherence assay. Antibody responses were found to depend not only on the ganglioside used as an immunogen but also on the mouse strain. Gangliosides having a trisaccharide sequence (NeuAc alpha 2----8NeuAc alpha 2----3Gal-) such as GD3, GD2, GD1b, GT1a and GQ1b, in particular O-Ac-GD3, induced high-titer antibody responses, whereas those having a disaccharide sequence (NeuAc alpha 2-- -3Gal-) such as GM4, GM3, GM2, GM1, GD1a and GT1b induced low-titer antibody responses. On the other hand, gangliosides with NeuGc developed minimum titers. In contrast, asialogangliosides induced much higher responses than the corresponding gangliosides. The differences in ceramide portions of these gangliosides did not appear to be involved in inducing antibody responses. Mice could be divided into three groups according to the magnitude of their antibody responses: Group 1, those that produce the highest antibody responses (C3H/HeN and A/J); Group 2, those that demonstrate moderate antibody titers (Balb/c, C57BL/6, DBA/2 and nu/nu Balb/c); and Group 3, those that make minimum responses (AKR/N, C3H/HeJ, CBA/N and NZB/N). The pattern of reactivity to the various gangliosides was similar in all the strains tested. PMID- 1584232 TI - Dissociation of primary antigen-antibody bonds is essential for complement mediated solubilization of immune precipitates. AB - The role of dissociation of primary antigen-antibody bonds in the solubilization of immune complexes (IC) has been investigated using photo-affinity crosslinked IC comprising NAP15-BSA and murine monoclonal anti-DNP antibodies. Non-covalently linked IC were solubilized rapidly when incubated with normal human serum (NHS), whereas covalently-linked IC were solubilized poorly or not at all. The rate and extent of complement activation produced by incubating covalently-linked and non covalently linked IC with NHS was similar as assessed by the production of the C1s:C1-inhibitor, C3:properdin and C5b-9 complexes and the anaphylatoxins C4a and C3a. Thus, the inability of serum to solubilize photo-affinity crosslinked IC must be due to failure of dissociation of primary antigen-antibody bonds. PMID- 1584233 TI - Nucleotide sequences and expression of cDNAs for a bovine anti-testosterone monoclonal IgG1 antibody. AB - cDNAs coding for the heavy and light chains of a bovine anti-testosterone IgG1 monoclonal antibody have been cloned and sequenced. These cDNAs are the first to be reported for functionally rearranged bovine immunoglobulin genes. Testosterone binding by the antibody encoded by the cDNAs has been verified by expression of the cDNAs in COS-1 cells and detection of anti-testosterone antibodies in transfected cell media using an ELISA specific for bovine anti-testosterone IgG. The derived protein sequence of the variable domains have suggested a possible binding model for the interaction between the antibody and testosterone. The derived protein sequence of the constant domains has been used to identify residues which could be involved in the selective transport of bovine IgG1 from blood plasma into colostrum at the time of parturition. PMID- 1584234 TI - Specific antigen binding by proteins secreted by an antigen-specific T cell hybrid. AB - Antigen-specific molecules secreted by a murine T cell hybrid specific for azobenzene arsonate (ABA) were purified from ascites fluid by ion exchange chromatography and affinity for antigen. The antigen-specific proteins were purified 250 fold and were resolved predominantly as Mr 110,000 polypeptides by reduction and SDS-polyacrylamide gel electrophoresis. The ability of these molecules to bind antigen was analyzed by an ELISA using antigen-coated microtiter trays. Binding of the T cell proteins to antigen was detected with antisera specific for the proteins. Antigen binding to ABA-ovalbumin but not ovalbumin was optimal at 37 degrees C and protein derived from another T cell hybrid did not bind ABA-ovalbumin. Solid phase antigen binding was inhibited specifically by soluble ABA-ovalbumin, indicating that these T cell-derived proteins bind nominal antigen in the solid or liquid phase. It is suggested that these proteins represent a soluble, antigen specific manifestation of some T cell function. PMID- 1584235 TI - When did Ray Kennedy's Parkinson's disease begin? AB - Ray Kennedy's Parkinson's disease probably began during his distinguished career as a professional soccer player at least 10 years before the first unequivocal physical signs and 14 years before the diagnosis was finally made, when he was 35 years old. Early prodromal symptoms included intermittent subtle disturbances of movement and posture affecting the right arm and leg, mild facial immobility, episodes of profound malaise and lack of energy, inner feelings of tremulousness, excessive unprovoked bouts of perspiration, and accompanying feelings of heat. Abnormalities of movement in the right arm can be seen in video footage of soccer games up to 8 years before his disability came to medical attention. Many of his premorbid personality traits are characteristic of those believed to be associated with the subsequent development of the malady. At least in some patients with Parkinson's disease, the search for instigating aetiological factors should focus 10-20 years before the cardinal signs can be recognised with certainty. PMID- 1584236 TI - Movement disorders as sequelae of central pontine myelinolysis: report of three cases. AB - In three survivors of central pontine myelinolysis, dystonia (in two patients) and rest tremor (in one) were sequelae. The onset of these movements occurred 3 weeks to 5 months after the initial presentation with central pontine myelinolysis. Magnetic resonance imaging revealed basal ganglia lesions suggestive of extra-pontine myelinolysis in all three patients. We propose that the movement disorders seen in our cases are clinical correlates of extra-pontine myelinolysis. PMID- 1584237 TI - Exposure to well water and pesticides in Parkinson's disease: a case-control study in the Madrid area. AB - Past exposure to well water and pesticides was assessed in 128 unselected Parkinson's disease (PD) patients and 256 age and sex-matched controls. All were residents in a defined urban area of Madrid, Spain. In keeping with other reports, we found that exposure to well water might be a factor associated with the likelihood of developing PD, though only prolonged exposures of 30 years or longer were significantly different between PD and controls (p less than 0.02). In contrast, past exposure to pesticides did not appear to be associated with an increased risk of developing PD. Prolonged well water drinking antedating the development of PD was not associated with early onset of the disease, nor did such cases progress to greater disability. Future case-control studies addressing prolonged well water consumption as a risk factor in PD should look for differences in the content of substances other than pesticides in the water as determined by the source of water to which patients may have been specifically exposed. PMID- 1584239 TI - Hemifacial spasm due to peripheral injury of facial nerve: a nuclear syndrome? AB - Four cases of hemifacial spasm (HFS) are reported. The spasm followed a few months after injury to a peripheral branch of the seventh nerve. An EMG examination of facial muscles disclosed the typical finding of HFS: spontaneous activity, paradoxical cocontraction, and diffusion of spontaneous or provoked blinking. A nuclear involvement, secondary to the nerve lesion, is the most likely pathophysiological explanation for similar cases in HFS. PMID- 1584238 TI - Interlimb coordination in Parkinson's disease. AB - This study examined the degree to which Parkinson's disease (PD) patients could "spatially link" the upper limbs to facilitate the performance of bimanual simultaneous movements. Six right-handed PD patients, and seven normal age- and sex-matched controls performed three different tasks: (a) an isotonic elbow flexion as rapidly as possible through an angle of 30 degrees; (b) an isometric contraction of the flexor muscles at the elbow joint to 40% and 60% of maximal volitional force (MVF) for a period of 5 s; (c) an isometric contraction for 2.5 s with one limb, then simultaneously performing an isotonic flexion with the contralateral limb while maintaining the isometric contraction for 2.5 s more. As expected, PD patients were significantly slower in performing the isotonic movement and produced lower peak velocities than the controls. More importantly, the two groups were differentially affected during the bimanual condition. In normals, movement time decreased and peak velocity increased in the bimanual condition. In contrast, PD patients showed increased movement times and sometimes decreased peak velocities in the bimanual condition. The results suggest that normal subjects utilize bilateral outflow to symmetrical muscle groups to synchronize the two limbs in the bimanual task, whereas PD patients dissociate the two limbs. PMID- 1584240 TI - Encapsulated cell implantation for Parkinson's disease. PMID- 1584241 TI - Reading as a "trick" for relieving blepharospasm. PMID- 1584242 TI - Brachial plexus palsy associated with spasmodic torticollis in a patient with tomaculous neuropathy. PMID- 1584243 TI - Pallidal and putaminal lesions resulting from disulfiram intoxication. PMID- 1584244 TI - Dystonia and reflex sympathetic dystrophy induced by ergotamine. PMID- 1584245 TI - Pathophysiology of cerebellar ataxia. AB - Human and animal experiments performed recently have resulted in a more detailed understanding of limb movement and body posture disorders associated with cerebellar dysfunction. The delay in movement initiation can be explained by a delay in onset of phasic motor cortex neural discharge owing to decreased input from the cerebellar hemispheres. Disorders of movement termination (dysmetria), which can occur for movements at proximal and distal joints, result from disturbances of the timing and intensity of antagonist electromyographic (EMG) activity necessary to break the movement. Disorders in velocity and acceleration of limb movements result from muscular activity that is smaller in amplitude and more prolonged. The cerebellum is important for control of constant force but not for generation of maximal force. Dysdiadochokinesia is explained by a combination of the above mentioned mechanisms. During complex movements in three-dimensional space, the cerebellum contributes to timing between single components of a movement, scales the size of muscular action, and coordinates the sequence of agonists and antagonists. The basic structure of motor programs is not generated in the cerebellum. Hypotonia can be observed only in acute cerebellar lesions. Cerebellar tremor appears to result from a central mechanism, but is modulated or provoked through increased long-loop EMG responses. The common assumption that cerebellar ataxia of stance does not improve with visual feedback is true only of vestibulocerebellar lesions, not for ataxia resulting from atrophy of the anterior lobe of the cerebellum. PMID- 1584246 TI - Human myoblast transplantation: preliminary results of 4 cases. AB - Myoblasts from immunocompatible donors have been transplanted into the muscles (tibialis anterior, biceps brachii, and/or extensor carpi radialis longus) of 4 Duchenne patients in the advanced stages of the disease. Although no immunosuppressive treatment was used, none of the patients showed any clinical signs of rejection such as fever, redness, and inflammation. One patient transiently produced antibodies against the donor myoblasts as determined by cytofluorometric analysis. This patient and 2 others were shown to form antibodies against their donor's myotubes. Muscle biopsies of the injected tibialis anterior of 4 patients revealed that 80%, 75%, 25%, and 0% of the muscle fibers, respectively, showed some degree of dystrophin immunostaining. The contralateral noninjected muscles of the latter 3 patients did not contain any dystrophin positive fibers, while that of the first patient showed dystrophin expression in 16% of the fibers examined. Myoblasts were also injected into the extensor carpi radialis longus or the biceps brachii of these patients. A few months subsequent to injection, one patient was shown to have a 143% increase of strength during static wrist extension. This result must be interpreted with caution because a double-blind strength-measuring protocol was not used. Furthermore, we have noted that this change slowly decayed over time. The strength of 2 other patients was increased less remarkably (41% and 51%), while the strength of the fourth patient was unchanged. PMID- 1584247 TI - Eosinophilia-myalgia syndrome: myopathic electrodiagnostic characteristics. AB - Eosinophilia-myalgia syndrome (EMS) is a disorder characterized by generalized muscle pain and eosinophilia. The etiology of this syndrome appears to be related to the ingestion of L-tryptophan. Most studies to date describe an associated peripheral neuropathy or combined myopathy and peripheral neuropathy. This report presents 2 EMS patients with myopathy, confirmed by muscle biopsy in 1 case and electrophysiology in both cases. No clinical evidence of neuropathy was found. Both routine and single fiber electromyography failed to demonstrate abnormalities, suggesting neuropathy. Electrodiagnostic abnormalities paralleled the clinical course. After 10 months, both patients continued to have symptoms of muscle cramping and reduced endurance, with mild electromyographic abnormalities, perhaps reflecting changes in their motor unit. PMID- 1584248 TI - Median--ulnar nerve communications and anomalous innervation of the intrinsic hand muscles: an electrophysiological study. AB - One hundred (100) left arms were examined for median-to-ulnar or ulnar-to-median nerve anastomoses using surface electrodes. Muscles innervated by the anastomosis were determined using a concentric needle electrode. We found a motor median-to ulnar nerve anastomosis in the forearm in 32% of the cases (Martin-Gruber anastomosis, MGA). No case of motor ulnar-to-median nerve anastomosis in the forearm could be found. The MGA mainly innervated muscles, which are normally supplied by the ulnar nerve. The high incidence of MGA in this study shows that all clinically relevant motor median-to-ulnar nerve communications in the forearm can be detected using surface electrodes in routine examinations. Stimulus spread must be looked for and eliminated by the methods described. PMID- 1584249 TI - Skeletal muscle regeneration after crush injury in dystrophic mdx mice: an autoradiographic study. AB - The X-linked dystrophic animal model, the mdx mouse, shows an extraordinary capacity for sustained muscle regeneration compared with X-linked dystrophic golden retriever dogs and humans with Duchenne muscular dystrophy. To test the hypothesis that muscles of mdx mice might have inherently superior muscle regeneration to that in nondystrophic animals, muscle regeneration in response to a crush injury was examined in mdx mice and in the nondystrophic, parental strain C57Bl/10Sn. Autoradiographic techniques were used specifically to investigate the timing of muscle precursor replication after crush injury. Little difference in the regenerative capacity, either histologically or with respect to the timing of muscle precursor replication, was found between mdx mice and C57Bl/10Sn or other nondystrophic strains of mice. PMID- 1584250 TI - Comparison of electric and magnetic coil stimulation in the supraclavicular region. AB - We compared the compound motor action potentials (CMAPs) evoked in the biceps, triceps, and abductor digiti minimi (ADM) muscles by conventional electrical stimulation at Erb's point (EP), and by magnetic coil stimulation of the supraclavicular region in 11 normal subjects. We found that magnetic coil stimulation was less effective than conventional stimulation in activating motor fibers in the brachial plexus in 45% of the recordings analyzed. CMAP amplitudes greater than those obtained with EP electrical stimulation were seen in 16% of recordings with supraclavicular magnetic stimulation, and in 33% of recordings with cervical magnetic stimulation, indicating that EP electrical stimulation is submaximal in a large proportion of cases. PMID- 1584251 TI - The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy. AB - We report a study, assessing involvement of the heart in 33 familial cases of Becker muscular dystrophy (BMD), 31 familiar cases of facioscapulohumeral (FSH) dystrophy, and 27 familial cases of Bethlem myopathy. In the patients with BMD, correlations of myocardial involvement with age and extent of musculoskeletal involvement were made. We performed physical examination, chest x-ray, electrocardiographic (EKG), and echocardiographic examination on all patients, and continuous EKG Holter-monitoring in the patients with FSH dystrophy. Thirteen patients with BMD (45%) showed EKG changes similar to those found in Duchenne muscular dystrophy. Only 1 of the 13 individuals with cardiac involvement was wheelchair-bound. We found no evidence of cardiac changes in the patients with FSH dystrophy. In Bethlem myopathy, only 1 patient had a form of hypertrophic cardiomyopathy (asymmetrical septal hypertrophy). PMID- 1584252 TI - Phrenic nerve conduction studies. AB - To refine the technique of phrenic nerve conduction, we first studied electrode positioning and sources of chest wall artifact. Diaphragmatic compound motor action potentials (DCMAPs) were mapped at close intervals over 4 hemithoraces of two subjects, finding optimum recording sites which were then used to quantitate artifacts due to EKG, chest wall EMG, and configurational thoracic changes of respiration. Based on these findings, 20 normal subjects were studied, showing ease of application and good side-to-side agreement for DCMAP latencies; but, in contrast to prior reports, right-to-left correlation for amplitude and waveform was poor, making the unaffected side an unreliable standard in unilateral partial phrenic nerve lesions. PMID- 1584253 TI - Spinal fusion in Duchenne muscular dystrophy: a multidisciplinary approach. AB - We studied 27 Duchenne muscular dystrophy patients having spinal fusion for scoliosis. One patient died intraoperatively of cardiac arrest; all others have done well with no instances of malignant hyperthermia, postoperative ventilatory system dependence, pneumothorax, persisting infection, neurologic damage, nonunion, or pain. The anesthetic management included primarily intravenous general anesthetics with minimal myocardial depressant effects, avoiding succinylcholine and inhalation agents. Preoperative cardiac studies aided anesthetic management intra-operatively. There was an almost universal sinus tachycardia. Holter monitoring defined 4 of 16 with ventricular premature beats, 4 of 16 with atrial premature beats, and no ventricular tachycardia or atrial flutter or fibrillation. Echocardiogram demonstrated mitral prolapse in 2 of 22, frequent abnormal systolic performance with abnormal shortening fraction less than 28% in 7 of 16, and reduced rate-corrected velocity of fiber shortening in 9 of 15. Afterload was elevated in 7 of 15. The mean forced vital capacity (FVC) preoperatively was 45.3 +/- 15.9% with continuing diminution to 28.7 +/- 14.9% at 3.3 +/- 2.2 years after surgery. The main benefit of surgical stabilization is the relative ease and comfort of wheelchair seating compared with those nonoperated patients who develop progressive deformity. We have not seen lasting improvement or stabilization in FVC following surgery as decreasing function is related primarily to muscle weakness. PMID- 1584254 TI - Lead uptake in motor axons. AB - In an attempt to determine whether lead (Pb) in striated muscle can be taken up by motor axon, mice were injected intramuscularly with a 5% Pb nitrate solution, and the passage of Pb through the tissues was traced with electron microscopy. Thirty minutes after injection in the tibialis anterior muscle, Pb was seen at the sarcolemma and axolemma of the neuromuscular junction (NMJ) and in the adjacent sarcoplasmic reticulum (SR). Pb was also present in the axoplasm and mitochondria of terminal and preterminal motor axons. The presence of Pb was confirmed with x-ray elemental microanalysis. The results indicate that there is a pathway for intramuscular Pb to enter terminal motor axons. This supports the hypothesis that some forms of motor neuron disease (MND) may be due to axonal uptake and retrograde transport of Pb. PMID- 1584255 TI - Motor-evoked responses in primary lateral sclerosis. AB - Primary lateral sclerosis (PLS) may be distinguished on the basis of clinical and pathological features from amyotrophic lateral sclerosis (ALS). The former is featured by a much longer clinical course, exclusively upper motor neuron findings, losses of precentral pyramidal neurons, and preservation of anterior horn cells. Electrophysiological studies of 7 PLS cases have shown normal peripheral motor conduction, absent or very delayed motor-evoked potentials, the occasional late development of denervation activity in distal muscles, and normal somatosensory-evoked potentials. PMID- 1584256 TI - Case-of-the-month: perineuritis presenting as mononeuritis multiplex. AB - Perineuritis unassociated with other significant pathological changes is a rare finding. A patient is described with mild, non-insulin dependent diabetes mellitus who presented with the clinical picture of mononeuritis multiplex, and in whom perineuritis but no occlusive vascular disease was found on sural nerve biopsy. Treatment with prednisone and plasma exchange resulted in some improvement. We conclude that the focal perineuritis, rather than the diabetes, was responsible for the clinical picture mimicking mononeuritis multiplex. In conjunction with previous reports, this suggests that perineuritis may be a treatable neuropathy. PMID- 1584257 TI - Magnetic resonance imaging of angiographically occult runoff vessels in peripheral arterial occlusive disease. AB - BACKGROUND: Bypass grafting to arteries of the lower leg has become standard surgical management of advanced peripheral vascular disease. Its success depends on identifying suitable distal vessels. Preoperative preparation includes imaging of the arteries of the lower leg, usually by conventional contrast arteriography. An alternative procedure, magnetic resonance (MR) angiography, has been successfully employed in patients with various cardiovascular diseases, but its possible value in patients with peripheral vascular disease has received little attention. METHODS: We used both conventional and MR angiography in preoperative studies of the lower-leg vessels of 23 patients (25 legs) with peripheral arteriosclerosis and arterial insufficiency, and developed independent therapeutic plans based on the information provided by each technique. When the plans differed, the interventional procedure judged more likely to save the limb was performed. The findings of conventional and MR angiography were verified by intraoperative arteriography, postinterventional arteriography, or direct operative exploration. RESULTS: MR angiography detected all vessels identified by conventional angiography, whereas conventional arteriography failed to detect 22 percent of the runoff vessels identified by MR angiography. The detection by MR angiography of vessels not identified by conventional angiography altered the surgical management of the disorders of four patients (17 percent) and guided successful bypass procedures. CONCLUSIONS: MR angiography is a noninvasive technique with greater sensitivity than conventional contrast arteriography for detecting distal runoff vessels in patients with peripheral arterial occlusive disease. PMID- 1584258 TI - Endoscopic biliary drainage for severe acute cholangitis. AB - BACKGROUND: Emergency surgery for patients with severe acute cholangitis due to choledocholithiasis is associated with substantial morbidity and mortality. Because recent results suggested that emergency endoscopic drainage could improve the outcome of such patients, we undertook a prospective study to determine the role of this procedure as initial treatment. METHODS: During a 43-month period, 82 patients with severe acute cholangitis due to choledocholithiasis were randomly assigned to undergo surgical decompression of the biliary tract (41 patients) or endoscopic biliary drainage (41 patients), followed by definitive treatment. Hospital mortality was analyzed with respect to the use of endoscopic biliary drainage and other clinical and laboratory findings. Prognostic determinants were studied by linear discriminant analysis. RESULTS: Complications related to biliary tract decompression and subsequent definitive treatment developed in 14 patients treated with endoscopic biliary drainage and 27 treated with surgery (34 vs. 66 percent, P greater than 0.05). The time required for normalization of temperature and stabilization of blood pressure was similar in the two groups, but more patients in the surgery group required ventilatory support. The hospital mortality rate was significantly lower for the patients who underwent endoscopy (4 deaths) than for those treated surgically (13 deaths) (10 vs. 32 percent, P less than 0.03). The presence of concomitant medical problems, a low platelet count, a high serum urea nitrogen concentration, and a low serum albumin concentration before biliary decompression were the other independent determinants of mortality in both groups. CONCLUSIONS: Endoscopic biliary drainage is a safe and effective measure for the initial control of severe acute cholangitis due to choledocholithiasis and to reduce the mortality associated with the condition. PMID- 1584259 TI - Induction of labor as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group. AB - BACKGROUND: The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies. It is not known, however, whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor. METHODS: We studied 3407 women with uncomplicated pregnancies of 41 or more weeks' duration. The women were randomly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise, in which case labor was induced or cesarean section was performed. In the induction group, labor was induced by the intracervical application of prostaglandin E2. Serial antenatal monitoring consisted of counts of fetal kicks, nonstress tests, and assessments of amniotic-fluid volume. The outcomes we measured were the rates of perinatal mortality, neonatal morbidity, and delivery by cesarean section. RESULTS: Among the 1701 women in the induction group, 360 (21.2 percent) underwent cesarean section, as compared with 418 (24.5 percent) of the 1706 women in the monitoring group (P = 0.03). This difference resulted from a lower rate of cesarean section performed because of fetal distress among the women in the induction group (5.7 percent vs. 8.3 percent, P = 0.003). When two infants with lethal congenital anomalies were excluded, there were no perinatal deaths in the induction group and two stillbirths in the monitoring group (P not significant). The frequency of neonatal morbidity was similar in the two groups. CONCLUSIONS: In post-term pregnancy, the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management. PMID- 1584260 TI - Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. AB - BACKGROUND: The efficacy of conventional treatment with surgery and radiation for cancer of the esophagus is limited. The median survival is less than 10 months, and less than 10 percent of patients survive for 5 years. Recent studies have suggested that combined chemotherapy and radiation therapy may result in improved survival. METHODS: This phase III prospective, randomized, and stratified trial was undertaken to evaluate the efficacy of four courses of combined fluorouracil (1000 mg per square meter of body-surface area daily for four days) and cisplatin (75 mg per square meter on the first day) plus 5000 cGy of radiation therapy, as compared with 6400 cGy of radiation therapy alone, in patients with squamous-cell carcinoma or adenocarcinoma of the thoracic esophagus. The trial was stopped after the accumulated results in 121 patients demonstrated a significant advantage for survival in the patients who received chemotherapy and radiation therapy. RESULTS: The median survival was 8.9 months in the radiation-treated patients, as compared with 12.5 months in the patients treated with chemotherapy and radiation therapy. In the former group, the survival rates at 12 and 24 months were 33 percent and 10 percent, respectively, whereas they were 50 percent and 38 percent in the patients receiving combined therapy (P less than 0.001). Seven patients in the radiotherapy group and 25 in the combined-therapy group were alive at the time of the analysis. The patients who received combined treatment had fewer local (P less than 0.02) and fewer distant (P less than 0.01) recurrences. Severe and life-threatening side effects occurred in 44 percent and 20 percent, respectively, of the patients who received combined therapy, as compared with 25 percent and 3 percent of those treated with radiation alone. CONCLUSIONS: Concurrent therapy with cisplatin and fluorouracil and radiation is superior to radiation therapy alone in patients with localized carcinoma of the esophagus, as measured by control of local tumors, distant metastases, and survival, but at the cost of increased side effects. PMID- 1584261 TI - The frequency of uniparental disomy in Prader-Willi syndrome. Implications for molecular diagnosis. AB - BACKGROUND: Prader-Willi syndrome is a genetic disorder characterized by infantile hypotonia, obesity, hypogonadism, and mental retardation, but it is difficult to diagnose clinically in infants and young children. In about two thirds of patients, a cytogenetically visible deletion can be detected in the paternally derived chromosome 15 (15q11q13). Recently, patients with Prader-Willi syndrome have been described who do not have the cytogenetic deletion but instead have two copies of the 15q11q13 region that are inherited from the mother (with none inherited from the father). This unusual form of inheritance is known as maternal uniparental disomy. Using molecular genetic techniques, we sought to determine the frequency of uniparental disomy in Prader-Willi syndrome. METHODS: We performed molecular analyses using DNA markers within 15q11q13 and elsewhere on chromosome 15 in 30 patients with Prader-Willi syndrome who had no cytogenetically visible deletion. We also studied their parents. Three patients with Prader-Willi syndrome who had a cytogenetic deletion served as controls. RESULTS: In 18 of the 30 patients without a cytogenetic deletion (60 percent), we demonstrated the presence of maternal uniparental disomy for chromosome 15 and its association with advanced maternal age. In another eight patients (27 percent), we identified large molecular deletions. The remaining four patients (13 percent) had evidence of normal biparental inheritance for chromosome 15; three of these patients were the only ones in the study who had some atypical clinical features. CONCLUSIONS: In about 20 percent of all cases, Prader-Willi syndrome results from the inheritance of both copies of chromosome 15 from the mother (maternal uniparental disomy). With the combined use of cytogenetic and molecular techniques, the genetic basis of Prader-Willi syndrome can be identified in up to 95 percent of patients. PMID- 1584262 TI - Advances in neurology (1). PMID- 1584263 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 24-1992. A 52-year-old man with hypertension, hypokalemia, and an adrenal mass. PMID- 1584264 TI - The potential role of magnetic resonance imaging in ischemic vascular disease. PMID- 1584265 TI - Therapeutic gastrointestinal endoscopy. Problems in proving efficacy. PMID- 1584266 TI - Management of post-term pregnancy. PMID- 1584267 TI - Treatments for esophageal cancer. PMID- 1584268 TI - Angioplasty versus medical therapy for single-vessel coronary artery disease. PMID- 1584269 TI - Angioplasty versus medical therapy for single-vessel coronary artery disease. PMID- 1584270 TI - Angioplasty versus medical therapy for single-vessel coronary artery disease. PMID- 1584271 TI - Angioplasty versus medical therapy for single-vessel coronary artery disease. PMID- 1584272 TI - Computer interpretation of electrocardiograms. PMID- 1584273 TI - Computer interpretation of electrocardiograms. PMID- 1584274 TI - Familial dilated cardiomyopathy. PMID- 1584275 TI - Manipulating the immune system with immune globulin. PMID- 1584276 TI - Manipulating the immune system with immune globulin. The National Institute of Child Health and Human Development. Intravenous Immunoglobulin Study Group. PMID- 1584277 TI - Nitric oxide as a mediator of relaxation of the corpus cavernosum. PMID- 1584278 TI - A rapid (but wrong) prenatal diagnosis. PMID- 1584279 TI - Environmental risks of chlorofluorocarbon anesthetic agents. PMID- 1584280 TI - Setting standards for the use of DNA-typing results in the courtroom--the state of the art. PMID- 1584281 TI - AIDS vaccine 'may not work' in Africa. PMID- 1584282 TI - AIDS helpline. Preventing exposure to disease. PMID- 1584284 TI - Care-giving during birth--midwifery. PMID- 1584283 TI - Local factors that affect wound healing. PMID- 1584286 TI - Writing a research proposal. PMID- 1584285 TI - The hurdles faced by black students. PMID- 1584287 TI - Respiratory complications of spinal anaesthesia and epidural analgesia. PMID- 1584288 TI - A glance at herbal remedies. PMID- 1584289 TI - The rights of nurses. Part 2. PMID- 1584290 TI - [Health promotion in adolescent students]. AB - Student health services offer excellent opportunities for health promotion. Besides the contact with students who attend the clinic because of illness, and thus present an opportunity for individual health promotion, relatively easy contact can be made with groups of healthy students at whom projects for health promotion can be aimed. It is imperative that these students, who are the parents of tomorrow, must be educated in health promotion in order to carry over a healthy life-style to a family and thus to the following generation. PMID- 1584291 TI - The AIDS epidemic--beyond the myths. PMID- 1584292 TI - Drug education and the media. PMID- 1584293 TI - The influence of strikes on rights. PMID- 1584295 TI - Sampling in nursing research. PMID- 1584294 TI - Should nurses strike? PMID- 1584296 TI - Managing aggression in the mentally retarded child. PMID- 1584297 TI - [Men in nursing]. PMID- 1584298 TI - Black patients in psychiatric hospitals. PMID- 1584299 TI - [Effect of vitamins B2 and B6 on the functional properties of cholinoreceptors in molluscan neurons]. AB - It is found that vitamins B2 and B6 modified the form of the acetylcholine response in identified Helix pomatia neurons. This effect is mainly conditioned by a delay in desensitization. PMID- 1584300 TI - [Change in the background afferent influx to the spinal cord after transsecting the sciatic nerve and early enhancement of monosynaptic reflexes]. AB - Background impulse activity (BIA) of separate fibres of dorsal roots of 5 lumbar segment of rats after one-sided cutting of the sciatic nerve which caused early enhancement of monosynaptic segmental reflexes (5 days after operation) has been recorded. It is revealed that afferent fibres with BIA are found more rarely on side of cutting than on the opposite side and frequency of background activity is lower than in the opposite root. It is concluded that development of spontaneous activity of the spinal ganglion neurons after cutting nerves does not ensure a higher BIA level in afferent fibres. The given phenomenon cannot be a reason of early enhancement of monosynaptic reflexes after the nerve cutting. PMID- 1584301 TI - [Efferent potential-dependent ionic currents developing in frog myoblast culture]. AB - Variety of outward voltage-dependent currents in cultured frog myoblasts were registered by means of whole cell voltage clamp. Six types of potassium currents (Ik) which reach the peak value (-10 mV) in 5, 12, 20, 30, 50 ms (fast) and do not reach the maximum in 7 s (slow) were established. High sensitivity to low temperature (+5 degrees) was shown for channels of very fast and of slow non inactivated Ik. The assumption is made that some of Ik--5, 20 and 30 ms to peak are especially characteristic of myoblasts fusion stage. PMID- 1584302 TI - [Neocortex neuronal reactions induced by substantia innominata stimulation in cats]. AB - Neuronal impulse activity in the sensorimotor cortex after Substantia Innominata (SI) stimulation has been studied in cats during conditioned placing with food reinforcement. SI stimulation was delivered 1 or 3 seconds before the conditioned sound stimuli. The results of the investigation show that SI stimulation does not change sensorimotor cortex impulse activity but at the same time it inhibits the background activity. Reactions of 32% (after 1 s) and 33% (after 3 s) of the somatosensory cortex neurones were increased to conditioned stimuli and conditioned movement after preliminary SI stimulation. The appearance of impulse responses in some neurones which showed no initial reactions to conditioned stimuli was caused by SI stimulation. Preliminary SI stimulation may cause not only excitatory but also inhibitory effect on somatosensory cortical neurones. In case of 1 s interval between SI stimulation and conditioned stimuli presentation there were only 6% of cells with such inhibition, but in case of 3 s interval there were 33% of such reactions. SI stimulation shortened the latencies of the conditioned movement 2-3 times. Modulatory influence of acetylcholine from SI neurones to neocortical activity is discussed. PMID- 1584304 TI - [All-Union Symposium "Neurophysiologic Mechanisms of Training"]. PMID- 1584303 TI - [Effect of parathyroid hormone on 45Ca2+ absorption in various rabbit tissues]. AB - The 45Ca2+ absorption by the different tissues under PTH influence was studied by the radioisotope method as dependent on the incubation time. In all cases it was found that the tissue faculty of 45Ca2+ accumulation increases especially in the early period of the incubation. This effect results from a more intense activity of the membrane channels. PMID- 1584306 TI - [Variations of neuronal responses in cat cerebral cortex to somatic stimulation in the presence of additional stimulants]. AB - Neuronal responses (areas 3, 4, 5) were registered in awake cats after electric stimulation of the contralateralis limb. External stimuli, food and defensive motivation inhibit short-latency neuronal reactions which were registered in control. When in the experiment there was electric stimulation of another limb instead of an external stimuli the neuronal reaction did not change. If subthreshold electric stimulation (SES) was given with a perceptible stimulation of such modality the spike neuronal responses appeared in either cases. This SES may be used as a conditional signal during defensive conditioning. It is established that the neuronal pattern under somatic stimulation is not constant. Its character is connected with fluctuation of cat's exteroceptive attention under external stimuli and internal motivational condition. PMID- 1584305 TI - [Effect of the vibrostimulation frequency on skin mechanoreceptors innervated with Abeta-, Adelta- and C-fibers]. AB - Vibrational stimulation of cat's skin by the frequencies of 10, 30 and 50 per second evoked response of mechanoreceptors innervated with A beta and A delta fibers, responding to each vibration stimulus. The higher vibrostimulation frequency, the more distinct changes appear in the "on"--and "off"--responses which are caused by a decreasing number of pulses for each vibration impact. The mechanoreceptors innervated with the C-fibers are not excited by these frequencies. After a preliminary vibrostimulation the part of mechanoreceptors innervated with C-fibers do not respond to the mechanical stimulus tested. The higher the frequency of preliminary vibrostimulation, the fewer receptors respond to the tested stimulus. PMID- 1584307 TI - [Interactions of the superior colliculus and the sensorimotor cortex in the alert rabbit]. AB - The tonic increased influence of the superior colliculus (SC) on the formation of visual responses of the sensorimotor cortex (SMC) was shown on the alert rabbits. It was shown that SC influence was realized through tectothalamocortical (nucleus lateralis posterior) canal relation. It was established that SMC of the alert rabbits in its turn exerts the inhibitory phasic influence on SC function. The obtained data are discussed in the light of participation of the colliculo cortical and cortico-collicular interactions in the organization of the visual motor coordination necessary for realization of the visual controlled behaviour. PMID- 1584308 TI - [Modulation of periaqueductal gray neuronal activity by influences of brain stem monoaminergic structures]. AB - Studies of spontaneous firing (SF) in the midbrain periaqueductal gray (PAG) neurons before and after stimulation of nucleus raphe magnus, locus coeruleus and substantia nigra were performed on the rat anesthetized with Hexenal (200 mg/kg). Three types of neurons different in SF structure were found. Stimulation of indicated structures increased SF rate in 11-14.5% and decreased 31-47% of the studied neurons of the third group. Simultaneous stimulation of two structures did not induce a remarkable increase of SF rate. If one of two simultaneously stimulated structures suppressed SF the ultimate effect was, as a rule, depression of SF. Greatest suppression of SF was observed if stimulation of nucleus raphe magnus was induced. Role of PAG in organization of the brain stem component of antinociceptive mechanism is discussed. PMID- 1584309 TI - [Distribution of GABA-immunoreactive elements in the reptile amygdaloid complex]. AB - GABA-immunoreactive (GABA-I) elements (neuronal somata and neuropile) are detected in turtle Emys orbicularis and lizard Ophysaurus spodus in all structures of ventral and dorsal parts of amygdaloid complex (AC) considered as phylogenetic more ancient and younger, respectively by means of the immunohistochemical method. Their maximal quantity in the ventral section of AC is found in the lateral region, lesser--in the ventral, central and medial regions. Besides in lizards a specialized laminar distribution of GABA-I elements in n. sphaericus is observed. GABA-I neurons are also detected in structures of dorsal part in turtles and lizards against the background of the immunopositive neuropile of a moderate density. It is supposed that GABA-ergic innervation of AC is liable to considerable variations in connection with taxonomic, ecological and other factors. PMID- 1584310 TI - [Identification of cholinoreceptors on the soma of RPa3 and LPa3 neurons in Helix lucorum]. AB - Selective cholinomimetics and cholinolytics were employed to identify cholinoreceptors on the somatic membrane in Helix lucorum RPa3 and LPa3 neurons using recording of transmembrane ionic currents. Agonists of nicotinic and muscarinic cholinoreceptors evoked reversible activation and following nonreversible inhibition of receptors (except carbamylcholine). Selective cholinomimetics were connected with the same membrane sites that were activated by acetylcholine. Nicotinic and muscarinic cholinolytics decreased the amplitude of inward current induced by acetylcholine (scopolamine and platyphylline had no effect). It is concluded that somatic membrane of RPa3 and LPa3 Helix neurons contains nicotinic and muscarinic cholinoreceptors. These receptors have several pharmacological peculiarities as compared with those of the vertebrates. Muscarinic cholinoreceptors of RPa3 and LPa3 neurons must be included into a special subtype that differs from well-known M1 and M2 subtypes. PMID- 1584311 TI - [Sources of cortical, hypothalamic and spinal serotoninergic projections: topical organization in the dorsal Raphe nucleus]. AB - Distribution of primuline, fast blue, fluoro-gold and nuclear yellow-labelled monoamine-containing cells in periventricular gray and dorsolateral tegmentum (including locus coeruleus) was studied in the rat after injection of these fluorochromes into the frontal cortex, hypothalamus and spinal cord. Combination of monoamine fluorescence method and retrograde cell-labelling was used. Two big groups of serotonin-positive cells projecting into the upper thoracic spinal segments were found in dorsomedial zone of the dorsal raphe. Part of these units also had divergent axon projections to the frontal cortex. Such cellular arrangement allows a supposition that analgetic effects of dorsal raphe stimulation can be partially based on the direct participation of this structure in the descending control at the spinal level. Neurones, sources of cortical projections are intermingled with the cells projecting to the hypothalamus but some topical differentiation can be distinguished. Neurotransmitter and neuroregulatory roles of separate cortical and hypothalamic projections of serotonin-containing neurons of the dorsal raphe cells is discussed. PMID- 1584312 TI - [Effect of magnesium ions on the functional state of postsynaptic membrane by modulation of the level of non-quantal secretion of the mediator]. AB - The role of non-quantal secretion (NS) of acetylcholine (ACh) in shortening of miniature end-plate currents (MEPC) after initial prolongation of MEPC due to acetylcholinesterase (AChE) inhibition was studied in the mouse diaphragm muscle under the voltage clamp conditions. Elevation of NS level by removal of magnesium ions from solution accelerated the shortening effect. After elimination of NS due to an increase of magnesium concentration up to 3 mmol/l the shortening of MEPC was absent. It was suggested that after AChE inhibition the magnesium ions in physiological range of concentrations can modulate the desensitization development on postsynaptic membranes by NS level regulation. PMID- 1584313 TI - Selenium in uremia: culprit or bystander? PMID- 1584314 TI - Effect of erythropoietin treatment on physical exercise capacity and on renal function in predialytic uremic patients. AB - Anemia is already present in patients with moderate renal failure and is a major cause of the decline in exercise capacity seen in these patients. We examined the effects of erythropoietin (EPO) treatment in 12 predialytic uremic patients (EPO group: mean age 46 +/- 12 years; 6 men, 6 women) with a mean glomerular filtration rate (GFR) of 10 +/- 4 ml/min x 1.73 m2. These patients were compared to a control group of 8 patients (5 men, 3 women). The observation period was 3 months. The EPO group received 300 U/kg body weight i.v. once a week. The EPO group increased their total hemoglobin (THb) from 323 +/- 89 to 466 +/- 128 g (p less than 0.001) and their hemoglobin concentration from 86 +/- 8 to 117 +/- 11 milligrams (p less than 0.001). Their exercise capacity, measured by a standardized exercise test on a bicycle ergometer, increased from 128 +/- 45 to 147 +/- 57 W (p less than 0.01). The control group did not change their THb (349 +/- 124 and 357 +/- 131 g), hemoglobin (93 +/- 8 and 94 +/- 10 milligrams) or exercise capacity (98 +/- 49 and 101 +/- 50 W) during the observation period. There was a significant correlation between the increase in THb and the increase in exercise capacity in the EPO group (r = 0.81, p less than 0.005). The GFR was unchanged in both groups (EPO group: 10 +/- 4 and 10 +/- 6 ml/min x 1.73 m2; control group: 8 +/- 3 and 8 +/- 3 ml/min x 1.73 m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584315 TI - Kinetics of aluminoxamine and feroxamine chelates in dialysis patients. AB - To achieve a rational basis for the use of deferoxamine (DFO) in aluminum (AL) and iron (Fe)-overloaded uremic patients, important insights may be provided by the recently available micromethods to determine DFO and its metallochelates aluminoxamine (AlA) and feroxamine (FeA). With this procedure, AlA and FeA plasma kinetics were evaluated in a pilot study in 10 uremic patients during a whole week after a single DFO infusion performed during the first hour of the first standard bicarbonate hemodialysis (HD) of the week. Patients were divided into normal (n = 6) and high (n = 4) ferritin groups (1 and 2 respectively). Baseline Al concentrations were greater than 2 less than 6 in group 1 and less than 1.5 mumol/l in group 2. DFO was given at doses of 40, 20 and 10 mg/kg. AlA and FeA showed substantially different kinetics. AlA kinetics were similar in group 1 and 2: they reached their peak at the beginning of the 2nd HD, decreased during the 2nd and 3rd HD, and with the highest DFO dose still increased between the 2nd and 3rd HD. At similar pre-DFO Al values (greater than 2 less than 3.3 mumol/l), increased DFO doses produced increased AlA concentrations ranging from 95 to 40% of total plasma Al for all the week. At higher pre-DFO Al values (greater than 3.5 less than 6 mumol/l), even a DFO dose as low as 10 mg/kg was sufficient to form consistent AlA amounts (from 80 to 15% of total Al).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584316 TI - Colchicine prevents kidney transplant amyloidosis in familial Mediterranean fever. AB - Twenty-one familial Mediterranean fever (FMF) patients who received a kidney transplant for terminal renal failure due to amyloidosis were studied retrospectively to evaluate the prophylactic effect of colchicine on graft amyloidosis. Proteinuria, highly suggestive of kidney transplant amyloidosis, developed in 11 patients within a median of 3 years after transplantation (range 0.5-10 years). In 10 patients, repeated urinalyses for protein were negative during a median of 5 years after transplantation (range 1-13). Patients who developed proteinuria or transplant amyloidosis received smaller colchicine doses than patients without proteinuria--mean 0.69 (range 0-1) versus 1.53 (range 1-2) milligrams per day (p = 0.0002), suggesting that colchicine prevents or delays development of transplant amyloidosis. This prophylactic effect of colchicine was complete at a dose of 1.5 mg/day or more and absent at a daily dose of 0.5 mg or less. In patients who received 1 mg/day, individual variability in the response to colchicine was observed. We conclude that the development of amyloidosis of the kidney transplant in FMF is inevitable at a colchicine dose lower than 1 mg/day, unpredictable at 1 mg/day and usually preventable with 1.5 mg/day or more. PMID- 1584317 TI - Calcium acetate versus calcium carbonate as phosphate binders in hemodialysis patients. AB - We conducted a randomized unblinded parallel clinical trial to compare the effectiveness, side effects and tolerance between calcium acetate (CA) and calcium carbonate (CC) in 80 stable chronic hemodialysis patients selected on the basis of their acceptable control of serum phosphorus (P) levels with aluminum hydroxide (AH). All patients were dialyzed against the same calcium dialyzate (1.62 mmol/l). The serum analytical tests included: calcium corrected to total protein, P, PTH (intact molecule) and bicarbonate. The study was divided into the following periods: P0: baseline measurements; P1: washout (withdrawal of AH for 15 days); P2: random allocation to CA and CC treatment at doses equivalent to 75 mEq of elemental calcium, stratified according to previous doses of AH (2 months); P3: adjustment of doses until control P (2 months). CA was poorly tolerated in 7 patients and CC in 2 (NS). The changes in serum P levels between P0 and P2 periods were lower in the CA group (1.73 +/- 0.25 vs. 1.80 +/- 0.50 mmol/l; p = 0.26) than in the CC group (1.77 +/- 0.35 vs. 1.93 +/- 0.48 mmol/l; p = 0.03, paired t test). Serum calcium was hardly modified by CA (2.42 +/- 0.20 vs. 2.47 +/- 0.17 mmol/l; NS) while in the CC group, it rose significantly (2.40 +/- 0.12 vs. 2.55 +/- 0.22 mmol/l; p = 0.0004). There were no differences in the control of PTH or bicarbonate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584318 TI - Haemodialysis-related porphyria cutanea tarda and treatment by recombinant human erythropoietin. AB - Haemodialysis-related porphyria cutanea tarda is a rare, but serious and mutilating skin condition, resulting from extremely high plasma porphyrin levels because of their inadequate clearance by haemodialysis. The treatment is very difficult as chloroquine is ineffective and venesection, the conventional treatment of this disease, is not always an option because of anaemia of end stage renal disease. We report a case of haemodialysis-related porphyria cutanea tarda and her successful management by recombinant human erythropoietin treatment. PMID- 1584319 TI - Immunoglobulin-E-specific suppressor factors in primary glomerulonephritis with nephrotic syndrome. AB - Human immunoglobulin (Ig) E synthesis is regulated by T-cell-derived binding factors which include potentiating factors and suppressor factors (IgE-SFs) and B cell-derived factors. Seventeen cases of primary glomerulonephritis (GN) with nephrotic syndrome and high serum IgE were studied for their serum IgE-SFs. These include 8 cases of minimal-change disease (MCD), 3 cases of IgM nephropathy, 4 cases of focal segmental glomerulosclerosis, and 2 cases of IgA nephropathy, aged between 20 and 60 years (mean: 37.2). A significantly lower activity of these factors was noted in the patient group as shown by a lower overall inhibition rate on in vitro IgE synthesis (median: 22.9 vs. 53.2%, p less than 0.05). Some of them even exhibited an enhancing activity in their serum as shown by a negative inhibition rate. These findings suggest that there is a T cell disorder in some of the primary GNs with high serum IgE, especially in MCD, which causes an abnormal regulation of IgE synthesis. PMID- 1584320 TI - Nephrotoxicity of germanium compounds: report of a case and review of the literature. AB - A 55-year-old woman was admitted to our hospital, complaining of general malaise, muscular weakness, anorexia and weight loss. She had a history of ingesting of a certain germanium (Ge) compound over the preceding 19 months, with a total dose of 47 g as Ge element. She was found to have renal failure (blood urea nitrogen, 44 mg/dl; serum creatinine, 2.6 mg/dl) without abnormal findings in urinalysis, and muscular and nervous damage. Initially, polymyositis was diagnosed and prednisolone administered. However, no improvement was seen, and neuromuscular symptoms and signs steadily worsened, ending in death. Microscopic study of the kidney showed that lipofuscin granules increased in the cells of the thick ascending limb of Henle's loop to the distal convoluted tubule accompanying mild tubular atrophy and that some of the tubules of these segments had vacuolar degeneration or desquamation. No apparent glomerular and vascular changes were observed. High Ge content was found in serum, urine and various tissues, e.g., spleen, liver, kidney, adrenal gland and myocardium, while in controls Ge could not be detected in sera, urine or tissues. We also review case reports about Ge toxicity, and discuss the pathogenesis of renal failure induced by Ge compounds. PMID- 1584321 TI - Treatment of hyperlipidemia with probucol suppresses the development of focal and segmental glomerulosclerosis in chronic aminonucleoside nephrosis. AB - We have recently reported that a lipid-lowering agent, probucol, reduces proteinuria in puromycin aminonucleoside (PA)-induced nephrotic rats (PAN). In this study, we examined whether a long-term treatment of hyperlipidemia with probucol can suppress the development of focal and segmental glomerulosclerosis (FSGS) in chronic PAN. A chronic PAN model was made with repeated intraperitoneal injections of PA (initially 100 mg/kg body weight followed by 25 mg/kg 5 times at 2-week intervals). Two weeks after the first injection of PA, either normal rat chow with or without 1% probucol was given to the nephrotic rats for 10 weeks. Chronic PAN exhibited remarkable proteinuria, hypoalbuminemia and severe hyperlipidemia with all lipoprotein fractions increased. Probucol treatment significantly reduced the lipid concentration in all major lipoproteins, significantly reduced proteinuria and increased plasma albumin concentration. Plasma albumin inversely correlated with cholesterol or phospholipid in low density and high-density lipoproteins, suggesting that the lipid-lowering effect of probucol may ameliorate the hypoalbuminemia associated with nephrosis. In light microscopic examination, various degrees of FSGS with tubulointerstitial lesions were observed in the renal cortex from chronic PAN. The degree of FSGS was scored from grades 1 to 4 according to severity. One half of the untreated PAN (4/8) was classified into grade 4 and the other into grades 2 or 3, whilst one half of treated PAN (4/8) was classified either into grade 1 or 2. The grading of FSGS correlated negatively with plasma albumin concentration. These results demonstrate that probucol is highly effective upon nephrotic hyperlipidemia and suggest that a long-term treatment of secondary hyperlipidemia can suppress progressive renal injury associated with chronic nephrosis. PMID- 1584322 TI - Effect of magnesium lithospermate B in rats with sodium-induced hypertension and renal failure. AB - To evaluate the antihypertensive effect of magnesium lithospermate B isolated from Salviae miltiorrhizae radix, determinations of blood pressure and urinary excretions of sodium, potassium, prostaglandin E2 (PGE2) and kallikrein, which have been proposed to play an important role in the regulation of blood pressure, were made in rats with sodium-induced hypertension and renal failure. In rats given magnesium lithospermate B, blood pressure was significantly decreased, whereas urinary excretion of electrolytes was significantly increased. Urinary PGE2 excretion following administration of magnesium lithospermate B increased as the dose of the compound was stepped up. The activity of kallikrein in urine was also increased by the treatment. From these results, the blood pressure-lowering action of magnesium lithospermate B may be due in part to enhancement of the kallikrein-prostaglandin system. PMID- 1584323 TI - Studies on serum renotropic activity after uninephrectomy in rabbits. AB - The present study was undertaken to critically examine the hypothesis that circulating renotropin is the primary stimulus for compensatory renal growth. Blood was collected before and after either left nephrectomy or sham operation from a total of 34 rabbits and the serum renotropic activity assessed by the uptake of 3H-thymidine in primary cultures of rabbit kidney cells. Sera obtained after uninephrectomy had significantly more renotropic activity than sera collected before surgery. In some cases, sera obtained after sham operation had more renotropic activity than those collected before, but the mean response was not increased after sham operation. The difference between sera collected before and after uninephrectomy was not transferrable to primary cultures of rabbit liver cells. These data confirm a modest but significant influence of uninephrectomy on the renotropic activity of blood in rabbits. PMID- 1584324 TI - Effects of the platelet-activating factor antagonists CV-6209 and CV-3988 on nephrotoxic serum nephritis in the rat. AB - Platelet-activating factor (PAF) is known as an important mediator in the pathogenesis of glomerular injury. In the present study, we evaluated the effect of the specific PAF antagonists CV-6209 and CV-3988 on accelerated nephrotoxic serum nephritis (NTN) in the rat. The amount of urinary protein excretion was significantly less in the rats treated with CV-6209 or CV-3988 on the 5th and 7th day of treatment than in the nontreated controls. The results of light- and immunofluorescence-microscopic examination did not demonstrate any favorable effect on glomerular changes by these PAF antagonists. However, CV-6209 protected against the loss of glomerular anionic charges in rats with NTN. Thus, it is suggested that PAF is a potent mediator of protein excretion, and that the loss of glomerular anionic charges is an important mechanism for the mediation of PAF in glomerulonephritis. PMID- 1584325 TI - Mechanisms of ciclosporin A-induced vasoconstriction in the isolated perfused rat kidney. AB - Hypertension is a well-known side effect of ciclosporin A (CsA). In the present study the mechanisms of vasoconstriction in renal vessels were examined in the isolated perfused rat kidney. Kidneys were perfused with constant flow at a temperature of 37 degrees C with Tyrode's solution equilibrated with 95% O2/5% CO2. CsA was dissolved in ethanol. 500 and 2000 ng/ml increased resistance of renal vessels by 0.97 +/- 0.55 x 10(5) and 2.29 +/- 1.33 x 10(5) dyn s cm-5, respectively (mean values +/- SD, n = 12). The vasoconstriction developed gradually over 4 min. The vasopressor effect of CsA was not changed by saralasin (10(-6) M), nifedipine (10(-6) M) and ketanserin (10(-6) M), but was completely blocked by phentolamine and prazosin (each 10(-6) M). CsA-induced vasoconstriction was not prevented by perfusion with Ca(2+)-free solution containing 2 mmol EGTA. Similarly, pretreatment with reserpine to deplete sympathetic nerve endings from catecholamines did not affect CsA-induced vasoconstriction. The findings suggest that CsA-induced vasoconstriction is mediated by stimulation of alpha 1-receptors. Ca2+ influx does not play a role for CsA-induced vasoconstriction. Prolonged perfusion of rat kidneys with the vehicle cremophor EL elicits an irreversible increase in perfusion pressure. PMID- 1584326 TI - Exacerbation of latent heart failure by mild hypocalcemia after parathyroidectomy in a long-term hemodialysis patient. AB - A 60-year-old uremic patient treated with hemodialysis for 13 years developed acute hypotension during hemodialysis and overt heart failure subsequently in a period of relatively mild hypocalcemia after parathyroidectomy. Blood pressure during hemodialysis was maintained by continuous calcium infusion alone. Cardiomegaly was improved by normalization of serum calcium. The cardiac complication is considered to be exacerbation of the underlying myocardial dysfunction by the acute decline of serum calcium which might be a feature of the 'hungry bone' syndrome. Latent myocardial dysfunction might be exacerbated by only mild hypocalcemia after parathyroidectomy in long-term hemodialysis patients. PMID- 1584328 TI - Protein C and its inhibitors during hemodialysis. PMID- 1584327 TI - ACE inhibitors and anaphylactoid reactions to high-flux membrane dialysis (AN69): clinical aspects. PMID- 1584329 TI - Effects of azathioprine on ciclosporin metabolism. PMID- 1584330 TI - Abdominal fat aspiration for diagnosis of amyloidosis. PMID- 1584331 TI - Acute interstitial nephritis and idiopathic cranial diabetes insipidus. PMID- 1584332 TI - Management of acute nephritis with the epsilon-aminocaproic acid: fact or epiphenomenon? PMID- 1584333 TI - Oxalate creatinine ratio in the peritoneal fluid of patients with primary hyperoxaluria. PMID- 1584334 TI - Sequential measurements of intestinal permeability to [51Cr]EDTA in children with Henoch-Schonlein purpura nephritis. PMID- 1584335 TI - Internal arteriovenous fistula saved by an arm splint. PMID- 1584336 TI - Asymmetry of brain aromatase activity: region- and sex-specific developmental patterns. AB - Developmental patterns of aromatase activity (AA) were characterized in individual forebrain regions of the rat at gestational day (GD) 22 and postnatal days (PN) 6 and 15. Aromatase activity was measured separately in homogenates of left and right preoptic area, anterior amygdaloid area, medial amygdaloid nucleus, anterior hypothalamic area and posterior hypothalamic area, by the tritiated water method with [1 beta-3H]-androstenedione as a substrate. Region- and sex-dependent asymmetries of AA with either left-to-right or right-to-left gradients were found. They change between GD22 and PN6 and PN15 according to region-specific patterns. Thus, AA of the male medial amygdaloid nucleus of the left side is higher at GD22, lower at PN6 and equal to the right side at PN15; in females, AA of the left side is lower than AA of the right side at GD22 and higher at PN6 and PN15. In preoptic area, a side difference (left side higher) was only detected in males. Asymmetries may result from differences in the expression of the enzyme by individual cell groups, or from differences in the number of cells per area expressing the enzyme. In either case, the stage dependent patterns of asymmetry in AA would be expected to influence sex steroid dependent differentiation processes in individual forebrain areas. PMID- 1584337 TI - Luteinizing hormone response to oxytocin is steroid-dependent. AB - Oxytocin-induced LH release from dispersed rat anterior pituitary cells in vitro was shown to be dependent on the steroidal environment. Preincubation of anterior pituitary cells with estradiol for 48 h enhanced the subsequent LH response to oxytocin (p less than 0.001). Maximal sensitization was observed with estradiol at 1 nM. Release of LH induced by oxytocin was inhibited in the presence of progesterone or to a greater extent in the presence of equimolar testosterone. Complete suppression of oxytocin-induced LH secretion occurred with 1 nM progesterone. Incubation of hemipituitaries with oxytocin revealed that the pituitary was sensitive in vitro to oxytocin at proestrus (p less than 0.05) but not at other stages of the cycle. The results indicate that there is altered sensitivity to oxytocin of the pituitary at different stages of the estrous cycle. Therefore activity of the neuropeptide in vivo might be modulated by steroids. PMID- 1584338 TI - Rapid gonadal recrudescence and body and lipid mass increases with hypothalamic lesions in photoregressed Siberian hamsters. AB - The effects of lesions (x) of the suprachiasmatic nucleus (SCN) or paraventricular nucleus (PVN), or pinealectomy (PINX) on gonadal recrudescence, body and fat pad weights, and food intake were examined in photoregressed male Siberian hamsters (Phodopus sungorus sungorus). Blood was sampled weekly for serum follicle-stimulating hormone (FSH) and prolactin (PRL) measurement. Lesions were classified as complete if greater than 80% of the nuclei were destroyed and designated as 'hits', whereas incomplete lesions were designated as 'misses'. Five weeks postlesion, hamsters with PVNx or SCNx hits and SCNx misses (lesions generally located caudal and dorsal to the SCN) had increased testes, epididymal white adipose tissue and body weights, increased food intake, and progressively increasing serum PRL, but not FSH concentrations compared with PINX, PVNx misses and intact short day controls. SCNx hamsters with complete lesions had sparse or arrhythmic locomotor activity patterns in subsequent tests under constant conditions. Although no single area was identified histologically as the locus for this effect, the hyperprolactinemia and rapid gonadal recrudescence was consistent with varied degrees of damage to the periventricular area. These results suggest a novel central control of PRL secretion by an area caudal and dorsal to the SCN, and extending to and including the PVN. This area may be involved with maintaining short day responses. PMID- 1584339 TI - Analysis of angiotensin II receptor subtypes in individual rat brain nuclei. AB - Previous studies have used new angiotensin II (AII) receptor subtype selective compounds to localize AII receptor subtypes within discrete rat brain nuclei. The purpose of this autoradiographic study was to extend these preliminary findings and provide a comprehensive analysis of AII binding sites in 22 rat brain nuclei and the anterior pituitary, to include estimates of the binding affinity for 125I sar1 ile8 AII (125I SIAII) at each nucleus, and determine the fractional distribution of each subtype at each nucleus. Estimates of KD in separate experiments revealed that AT1 nuclei had a consistently higher affinity for 125I SIAII than AT2 nuclei (0.66 vs. 2.55 nM). Displacement of subsaturating concentrations of 125I SIAII by 10(-8)-10(-4) M DuP753 (selective for the AT1 subtype) or PD123177 (selective for the AT2 subtype) indicated that approximately half of the brain regions surveyed contained predominantly AT1 sites and half contained predominantly AT2 sites. Binding was partially displaced by both compounds in several regions and two site analyses were performed to estimate the distribution of subtypes within each nucleus. The data were then corrected for differential occupancy by 125I SIAII. Brain nuclei associated with cardiovascular or dipsogenic actions of AII, e.g., subfornical organ, organum vasculosum of the lamina terminalis, median preoptic nucleus, nucleus of the solitary tract and area postrema, contained pure, or almost pure, populations of AT1 receptors. The functions of AII in brain regions containing predominantly AT2 binding sites, e.g., thalamus, colliculi, inferior olive and locus ceruleus, remain undefined. Thus, AII binding sites in the rat brain have been differentiated into two subtypes with similar characteristics to those reported in peripheral tissues. However, the unexpected finding that they can be differentiated on the basis of their affinity for 125I SIAII raises questions concerning their coidentity with peripheral receptor subtypes. PMID- 1584340 TI - Distribution of a renin-releasing factor in the central nervous system of the rat. AB - We have previously shown that the serotonergic regulation of renin secretion from the kidneys is mediated by a renin-releasing factor (RRF) that is present in both plasma and hypothalamus. The present studies were designed to determine the distribution of RRF in the brain and peripheral tissues and to test whether RRF release could be stimulated in vitro from hypothalamo-hypophyseal explants. RRF levels were determined in vitro by measuring renin release from kidney cortical slices. Addition of hypothalamic extract to rat kidney slices produced a dose dependent increase in renin release. RRF was measurable in most brain areas with the highest renin-releasing activity in the hypothalamus, cerebral cortex, medulla oblongata and cerebellum. To determine which brain regions contain RRF cell bodies, rats received an intracerebroventricular injection of colchicine to inhibit axonal transport and concentrate RRF in the perikarya. After colchicine treatment, RRF activity in the cerebral cortex, medulla oblongata and cerebellum decreased. In contrast, the hypothalamus had increased RRF activity suggesting that RRF cell bodies are localized in the hypothalamus. Superfusion of hypothalamo-hypophyseal explants with a high potassium Krebs-Ringer solution stimulated RRF release, suggesting that depolarization of hypothalamic neurons can stimulate RRF secretion. Nephrectomy produced a significant increase in RRF concentration in the hypothalamus, suggesting that RRF neurons respond to decreased renin activity or other kidney-related substances in the circulation. The determination of RRF in peripheral tissue revealed minimal renin-releasing activity in the liver, spleen and skeletal muscle extracts. High performance chromatography of hypothalamic extract on a GPC-100 column revealed RRF activity in fractions that were estimated to have a molecular weight of 5,000. These studies suggest that RRF-containing cell bodies in the hypothalamus respond to depolarization by releasing RRF into the circulation. In addition, the hypothalamic content of RRF is regulated by the kidney. Altogether, these data suggest that RRF neurons are part of a neuroendocrine system that regulates renin secretion from the kidneys. PMID- 1584341 TI - Increases in adrenolumbar venous flow and epinephrine secretion elicited by preoptic and hypothalamic stimulation in the cat. AB - Seventy-five sites were electrically stimulated within the preoptic and hypothalamic areas of anesthetized cats (n = 16). Adrenolumbar venous blood flow, secretion of epinephrine and norepinephrine, heart rate and mean arterial blood pressure were measured at baseline and following a standard stimulus (0.6 mA for 30 s) at each site. The most frequent adrenal medullary response to central stimulation was an increase in the secretion of both catecholamines (ng/min) greater than 10% of the baseline mean. Seventeen sites (23%) increased adrenolumbar venous flow greater than 12% above the mean baseline flow rate. This group of sites also evoked significantly greater increases in the secretion of epinephrine, and in mean arterial blood pressure and heart rate. These data support the hypothesis that secreted catecholamines, especially epinephrine, may act locally to increase blood flow through the adrenal medulla. PMID- 1584342 TI - Synaptic activation of rat supraoptic neurons by osmotic stimulation of the organum vasculosum lamina terminalis. AB - Intracellular recordings were obtained from neurons of the supraoptic nucleus in superfused explants of rat hypothalamus in vitro. Transient hyperosmotic stimulation of the organum vasculosum lamina terminalis (OVLT) area caused long lasting increases in the frequency of excitatory post-synaptic potentials and an associated rise in the rate of action potential discharge. Such responses could be evoked by small (less than + 2%) increases in osmolality, but not by isotonic solutions. These results suggest that the OVLT plays a functional role in the osmoregulation of neurohypophyseal hormone release. PMID- 1584343 TI - Transmaxillary-transnasal approach to the anterior clivus: a microsurgical anatomical model. AB - Numerous procedures to expose the anterior clival region have been described, including the transoral, transcervical, transseptal-transsphenoidal, transantral, transnasal, bilateral Le Fort I maxillotomy, transbasal, transpalatal, and modifications of the Caldwell-Luc approach. Despite the large number of surgical options available, it may be necessary to have wider access to the midline skull base than these approaches provide. We have developed a microsurgical transmaxillary-transnasal approach to the anterior clivus that has been studied in both dry skull and cadaveric preparations and used clinically. The surgical technique has four stages: 1) antromaxillary; 2) nasal; 3) sphenoidal; and 4) clival. The wider access of this approach is achieved mainly by an osteotomy of the frontal process of the maxilla, which transforms the nasal cavity and the antrum into a single cavity while preserving the functional anatomy of the nose. Cosmesis is preserved by replacement of the cartilaginous nasal septum and the frontal process at the end of the procedure. The technique provides the good cosmetic results of the sublabial approaches and prevents vascular and neural injury in the same way that other anterior approaches do. This transmaxillary transnasal technique may be used in combination with other approaches for extensive tumors. PMID- 1584344 TI - Histopathological study of balloon embolization: silicone versus latex. AB - Bilateral, symmetrical, experimental aneurysms were produced with anastomosed vein flap in the carotid arteries of 24 mongrel dogs. Aneurysms were occluded with latex or silicone balloons on each side and observed angiographically from 2 weeks to 2 months. A histopathological study was performed subsequently using light and scanning electron microscopy. Rupture after balloon embolization occurred in five aneurysms; all of which were incompletely occluded by a silicone balloon. On subsequent angiograms, four silicone balloons and one latex balloon were found to have migrated into the aneurysm, resulting in aneurysmal expansion. Parent artery occlusion was more common with latex balloons than silicone balloons. Histopathologically, residual fresh thrombi, decreased proliferation of fibroblasts within the aneurysmal cavity, and poor endothelialization were present around the silicone balloon. These results suggest that the intra aneurysmal organization, as seen in the aneurysm occluded by the silicone balloon, will be delayed because the balloon is not fixed within the aneurysm, and that this free-floating and rotating balloon causes repeated trauma to the aneurysm wall, contributing to subsequent enlargement and rupture of the aneurysm. The superior antithrombogenic nature of silicone may be responsible for the bias of such phenomena toward the silicone balloon. PMID- 1584345 TI - Spinal cord astrocytomas: results of therapy. AB - Spinal cord astrocytomas are rare lesions, usually of low grade, with a long natural history. Because of this, it is difficult to define the optimum approach to therapy based on available data. To provide more data, a retrospective review was performed. From 1975 through 1989, 21 patients were seen and treated (median age, 21 years), and 15 patients received radiation therapy after undergoing either biopsy or resection. The median time until death or the last follow-up examination was 41 months. The actuarial survival of all patients was 68% at 5 years. Of the five deaths, four were related to local tumor recurrence. The overall survival and recurrence-free survival of irradiated patients at 5 years was 57% and 44%, respectively. The age of the patient was a prognostic factor, with younger patients surviving substantially longer before recurrence. Of the 15 irradiated patients, 7 experienced recurrence of the tumor, which occurred within the irradiated portion of the spinal cord in all 7. Gross total resections were rarely achieved and, also, the extent of resection did not influence the risk for recurrence. In summary, we observed a long natural history for this disease, and although additional local therapy appears needed, it is unclear that either higher doses of radiation or more extensive surgery will decrease the risk of recurrence. PMID- 1584346 TI - Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling. AB - The clinical behavior of meningiomas with a high proliferative potential was analyzed to determine if the bromodeoxyuridine (BUdR) labeling index (LI) could be used to predict recurrence and the time to reoperation. Each patient received an intraoperative infusion of BUdR to label cells in DNA synthesis; the percentage of S-phase cells, or BUdR LI, of each tumor was determined immunohistochemically. Of 178 meningiomas studied, 53 had BUdR LIs greater than or equal to 1%. Of these 53 tumors, 21 were diagnosed histopathologically as malignant meningioma. Twenty-two percent of nonmalignant tumors and 81% of malignant tumors were recurrent or recurred after the BUdR study; repeat studies were performed in four patients. The mean BUdR LI of recurrent tumors was significantly higher than that of the nonrecurrent tumors [3.9 +/- 2.6 versus 1.9 +/- 1.0% (SD), P less than 0.005]. The recurrence rate was 100% for tumors with LIs greater than or equal to 5%, 55.6% for those with LIs of 3 to 5%, and 30.6% for those with LIs of 1 to 3%; the percentages of malignant meningiomas in these groups were 88%, 78%, and 19%, respectively. Logarithmic regression analysis showed that the time to reoperation (in months) can be predicted from the BUdR LI as: 70.0 x LI (%)-1.2 (R = 0.76). This formula can be used to estimate the doubling time of individual tumors and to predict the period of greatest risk of recurrence of meningiomas with a high proliferative potential. PMID- 1584347 TI - Generation of cytotoxic immune responses against a rat glioma by in vivo priming and secondary in vitro stimulation with tumor cells. AB - Cytotoxic T lymphocyte (CTL) responses to most antigens are generated by in vivo priming and secondary stimulation with antigen in vitro. The present studies were designed to determine whether that strategy could be used to stimulate development of CTL against brain tumors. Rats were primed with one of two tumors, RT2, an astrocytoma, or 9L, a gliosarcoma, and Corynebacterium parvum. Spleen cells from primed rats were stimulated with tumor cells and interleukin-2 in vitro to generate CTL. CTL generated against RT2 killed RT2 and 9L, but not allogeneic or histopathologically unrelated tumor cells, suggesting that the killing was brain tumor-specific and major histocompatibility complex gene product-restricted. Similar results were obtained with rats primed and secondarily stimulated with 9L. Specific cytotoxic cells only developed when syngeneic brain tumor cells were used for both priming and secondary stimulation. The cytotoxic cell populations were composed of OX-19+ T cells with a mixed CD4/CD8 phenotype. Controls consisting of spleen cells from unprimed or primed rats tested before culture exhibited low levels of cytotoxicity against brain tumor targets. Culturing unprimed or primed cells with interleukin-2 alone stimulated cell proliferation, but the cells that grew out exhibited only low levels of cytotoxicity for brain tumor cells. Cell populations exhibited consistent cytotoxicity against natural killer cell targets. None of the cell populations killed lymphokine-activated killer cell targets. The results demonstrated that brain tumor-specific CTL could be produced by priming in vivo followed by secondary stimulation with brain tumor cells in vitro. The results further demonstrated that RT2 and 9L share antigens that both induce and serve as target structures for specific cytotoxic cells. PMID- 1584348 TI - Human glioma-specific antigens detected by monoclonal antibodies. AB - Three murine monoclonal antibodies, designated GA-17, GB-4, and GC-3, were prepared by the hybridization of murine myeloma cells (NS-1) and spleen cells of BALB/c mice immunized with the crude membrane fraction of cultured human gliosarcoma cells (GI-1). Two of them (GA-17 and GB-4) reacted exclusively with the membrane of glioma cells, and the other (GC-3) reacted with the membrane of glioma cells and a T cell line (MOLT-4). Although these antibodies reacted with almost all of the gliomas, the reactions differed. GA-17 reacted equally well with all glioblastoma (17 cases) and low-grade astrocytoma (10 cases), whereas GB 4 reacted poorly with 7 cases of glioblastoma and GC-3 did not react with 7 cases of low-grade astrocytoma. The antigens, exclusively expressed on the cell surface, were analyzed by surface labeling with 125I followed by a cell lysis and immunoprecipitation with these antibodies. The findings obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GA-17, GB-4, and GC-3 reacted with Mr 140,000-145,000, Mr 160,000, and Mr 145,000-150,000 proteins, respectively. Some evidence has been obtained indicating that these antigens are composed of the same polypeptide chain (Mr 120,000) with the carbohydrate chains being different. PMID- 1584349 TI - Carbon dioxide reactivity in the evaluation of cerebral ischemia. AB - Carbon dioxide reactivity, as measured by transcranial Doppler, has been determined in a group of patients with carotid artery disease and compared to a control group. CO2 reactivity was readily evaluated using transcranial Doppler by having the patients breathe 5% CO2 via a rebreathing circuit. There were significant differences (P less than 0.01) between the symptomatic patients and asymptomatic controls, as well as between symptomatic and asymptomatic hemispheres (P less than 0.05) in the patients with carotid artery disease. Five patients had revascularization procedures with all showing improved CO2 reactivity in the symptomatic and asymptomatic hemispheres. The improvement occurred early in patients after carotid endarterectomy. Two patients demonstrated improved reactivity at 6 to 13 months after extracranial-to intracranial bypass. Transcranial Doppler has proven to be an easily performed and repeatable method of evaluating CO2 reactivity and its response to treatment. PMID- 1584350 TI - Noninvasive assessment of intracranial fistulas and other small arteriovenous malformations. AB - Twenty patients in whom the diagnosis of an intracranial arteriovenous malformation was suspected either by the history and clinical findings or by abnormal periorbital Doppler flow are discussed. Sixteen patients had only minor complaints or inconclusive signs or were clinically asymptomatic; 4 others presented with the syndrome of a carotid cavernous fistula. Patients were further examined by means of transcranial Doppler sonography, computed tomographic scanning, and cerebral angiography. In 17 patients, the diagnosis of an arteriovenous malformation could be established by transcranial Doppler sonography and could be confirmed by angiography. Transcranial Doppler sonography gave false negative results in 1 and false positive results in 2 patients. Our findings demonstrate the usefulness of modern ultrasound techniques in the assessment of small or even occult intracranial arteriovenous shunts before subjecting patients to more invasive procedures. PMID- 1584351 TI - Effect of intrathecal superoxide dismutase and catalase on oxyhemoglobin-induced vasospasm in monkeys. AB - A gel consisting of agarose and oxyhemoglobin (OxyHb) was developed so that, when placed in the subarachnoid space, OxyHb would be slowly released, simulating lysis of erythocytes after subarachnoid hemorrhage. The system was used to investigate the importance of reactions mediated by free radicals in the genesis of OxyHb-induced vasospasm in monkeys. Seventeen monkeys were randomly assigned to have subarachnoid placement, on Day 0, of one of the following: 1) agarose gel alone (n = 2); 2) agarose plus OxyHb (n = 3); 3) agarose plus OxyHb plus intrathecal administration of superoxide dismutase and catalase (n = 6); and 4) agarose plus OxyHb plus intrathecal administration of placebo (n = 6). Vasospasm was assessed by comparison of angiograms performed on Day 0 and 7 days after subarachnoid placement of compounds, and by electron microscopy. OxyHb alone caused significant reduction in the diameter of the middle cerebral artery (40 +/ 8%, P less than 0.005, paired t test), which was associated with ultrastructural damage to smooth muscle. Treatment with superoxide dismutase plus catalase or with placebo attenuated vasospasm of the middle cerebral artery, although significant narrowing persisted in both groups (27 +/- 12% and 26 +/- 13%, respectively, P less than 0.05, paired t test). Analysis of variance showed no difference in the degree of vasospasm between groups exposed to subarachnoid placement of OxyHb. Cerebrospinal fluid aspirated from the cisterna magna on Day 7 contained elevated activity of superoxide dismutase in animals that received treatment. Malondialdehyde was undetectable in cerebrospinal fluid after subarachnoid placement of agarose alone, although it was present in similar amounts in all groups that received subarachnoid placement of OxyHb. Since intrathecal superoxide dismutase and catalase failed to protect against OxyHb induced vasospasm, mechanisms mediated by free radicals may not be important in its genesis. As only one combination of doses of superoxide dismutase and catalase was administered, however, it may be that other dosage schedules might be efficacious. PMID- 1584352 TI - An assessment of the cerebral protective effects of etomidate in a model of incomplete forebrain ischemia in the rat. AB - The cerebral protective effects of etomidate were evaluated in a model of incomplete forebrain ischemia. Fourteen Wistar-Kyoto rats were anesthetized with halothane. After preparation, the rats were alloted to either the control group (halothane anesthesia, n = 7) or the etomidate group (n = 7). In the etomidate group, immediately before and during the period of ischemia, the animals received etomidate in sufficient concentration to achieve electroencephalogram burst suppression (loading dose, 7.5 mg/kg; infusion, 0.3-0.5 mg/kg/min). Both groups were subjected to a 10-minute ischemic insult accomplished by bilateral carotid artery occlusion and simultaneous hypotension (mean arterial pressure, 35 mm Hg). Histological evaluation of the brain was performed after a 4-day recovery period. Injury was evaluated in coronal brain sections in five structures: neocortex, striatum, reticular nucleus of the thalamus, and the CA1 and CA3 areas of the hippocampus. The location of the sections in the rostral-caudal axis was chosen to encompass anterior areas within the core of the ischemic territory as well as more posterior regions within the anticipated "watershed" zone between the occluded anterior and the intact posterior circulations. In the animals that received etomidate, statistically significant (P less than 0.05) reduction in the severity of the ischemic injury was observed in the CA3 area and in the ventral portion of the CA1 area of the hippocampus in the more posterior sections. There was an apparent trend toward protection in other structures in both rostral and caudal sections, but these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584353 TI - Vasogenic brain edema induced by arachidonic acid: role of extracellular arachidonic acid in blood-brain barrier dysfunction. AB - The effects of free arachidonic acid on the capillary permeability of normal rat brains were studied by measuring the regional uptake of [14C]aminoisobutyric acid by a quantitative autoradiographic technique. Intracerebral infusion of sodium arachidonate increased capillary permeability in a dose-dependent manner up to a concentration of 2 mmol/L. A high dose of arachidonic acid (more than 5 mmol/L) produced marked tissue destruction around the injection site (needle track) and increased capillary permeability less than 2 mmol/L arachidonic acid did. A time course study demonstrated that about 80% of the maximum increase in capillary permeability produced by arachidonic acid was observed within 2 hours after the infusion was initiated. In addition, capillary permeability gradually increased with time up to 24 hours, after which it declined to about half of the maximum increase 48 hours after infusion. These effects of arachidonic acid on capillary permeability were localized within about 1.6 mm around the injection site. Pretreatment with dexamethasone did not completely, but did significantly, inhibit the arachidonic acid-induced increase in capillary permeability. The inhibitory effect of dexamethasone was completely suppressed by the administration of actinomycin D, which inhibits de novo protein synthesis, 1 hour before the treatment with dexamethasone. These results suggest that arachidonic acid, which is released and accumulated in the extracellular space, increases the capillary permeability of the brain in at least two different ways. One is the direct action of the arachidonic acid itself, which can stimulate perturbation of the membrane of the capillary endothelial cells, thus promoting an increase in capillary permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584354 TI - Protrusio acetabuli in neurofibromatosis: nondysplastic and dysplastic forms. AB - Protrusio acetabuli (PA) in neurofibromatosis is not well documented in the literature. Two forms of PA, a nondysplastic and dysplastic type, are noted. Twenty-one percent of hips (13 patients) in neurofibromatosis were found to have some form of acetabular protrusion abnormality. In the control group (83 patients) without stigmata of neurofibromatosis, only 9% of hips were associated with PA. The progressive dysplastic form of PA is usually associated with contiguous soft-tissue neurofibromas and lumbar dural ectasia. The nondysplastic, nonprogressive form has less of an association with regional soft-tissue abnormalities and almost no association with dural dysplasia. PMID- 1584355 TI - Management of unruptured intracranial arteriovenous malformations: a decision analysis. AB - The management of unruptured intracranial arteriovenous malformations (AVMs) is controversial. Some authorities favor elective excision of the AVM before it bleeds, whereas others advise nonintervention unless the AVM bleeds, at which time surgical excision is performed in those who survive. A Markov model was developed that stimulates a clinical trial in which cohorts of patients with unruptured AVMs were assigned to either elective excision of their AVMs or conservative treatment (unless the AVM bled). Incremental utilities for both strategies were calculated at the end of each year after the beginning of the trial and are expressed as quality and risk-adjusted life years. The process was continued until all members of the cohorts had died. The mean quality and risk adjusted life expectancy for members of a cohort was calculated by dividing the total number of quality and risk-adjusted life years the cohort had accumulated by the size of the cohort. If the baseline values for surgical complications were used in the computation, the quality and risk-adjusted life expectancy for the surgical cohorts was at least 1 quality and risk-adjusted life year greater than for nonsurgical cohorts up to age 44. If a more favorable complication rate were used, elective surgery could benefit selected patients in their early 60s when the location and configuration of the AVM was favorable. Elective surgical resection is justified in many instances before rupture, particularly in young patients who have intracranial AVMs that have a favorable location, size, and venous drainage. PMID- 1584356 TI - Complex cranial base trauma resulting from recreational fireworks injury: case reports and review of the literature. AB - Two patients who sustained complex skull base trauma secondary to recreational fireworks injuries are reported. Initial assessment and management included axial and coronal computerized tomography, control of hemorrhage, debridement of wound and brain, isolation of brain from external environment, and reconstruction of the cranial base floor. Secondary orbital and facial reconstruction used available bone fragments and iliac bone graft in one patient and vascularized free tissue transfer in the other. In both patients, reconstruction of both the intracranial and extracranial compartments was successful with acceptable cosmetic result. Modification of multiple conventional approaches, along with a multispecialty surgical team, was used to deal effectively with these unique cases. PMID- 1584357 TI - Giant cell tumors of the sphenoid bone. AB - Giant cell tumors of the sphenoid are rare; there are 36 previously reported cases. We report two cases of these tumors in women in their thirties, both associated with pregnancy. In the first patient, the tumor was removed via a transnasal transsphenoidal approach. In the second patient, a Le Fort maxillotomy was required. In these cases, an interoperative diagnosis was made, and in both, this diagnosis directed surgical tactics towards a more radical excision. Reported experience with the outcome of giant cell tumors in other sites suggest that total removal by curettage is the ideal treatment; the main principle is to prevent local recurrence because the metastatic potential of this tumor is low. A combination of surgery and radiotherapy is essential for giant cell tumors occurring in sites where access is difficult, such as the sphenoid bone. Previous objections to radiotherapy have included poor response rate and malignant change. Recent studies suggest that neither of these problems is significant when modern therapeutic techniques are employed. PMID- 1584358 TI - An entirely suprasellar symptomatic Rathke's cleft cyst: case report. AB - An entirely suprasellar symptomatic Rathke's cleft cyst in a 21-year-old woman is reported. An unusual feature of this cyst was the fact that the subepithelial tissues were composed of pituitary gland cells. High resolution magnetic resonance imaging is sensitive in the detection of subtle suprasellar abnormalities. We review the literature regarding the embryological pathogenesis of Rathke's cleft cyst, with special reference to the entirely suprasellar type. PMID- 1584359 TI - Pituitary tumors and aneurysms: case report and review of the literature. AB - A case of acromegaly from a growth hormone-secreting pituitary adenoma associated with dilatation of all major intracranial arteries and bilateral giant, cavernous aneurysms is presented. Although saccular aneurysms are randomly associated with all types of pituitary tumors, the frequency of this happening with growth hormone-secreting or "chromophobe adenomas" is greater than would be expected by chance alone. Intrasellar saccular aneurysms contiguous with tumors have been reported. Bilateral cavernous carotid aneurysms have also occurred in association with pituitary tumors. Both infectious (bacterial and fungal) and traumatic aneurysms can develop as complications of pituitary surgery. A single case of aneurysms due perhaps to actual tumor infiltration of the arterial wall has been reported. Radiation therapy has rarely been associated with aneurysmal dilatation for nonpituitary tumors and has been reported only once after treatment of a pituitary tumor. Aneurysms may mimic pituitary tumors by producing endocrine disturbances, such as hypopituitarism, hyperprolactinemia, and diabetes insipidus, and by compressing adjacent cranial nerves. Anomalous large arteries, such as the trigeminal or transsellar-carotid variants, may run through the sella, and there is a case reported in which the former was associated with a pituitary tumor. A knowledge of these aneurysmal types and vascular anomalies is essential for the pituitary surgeon. Magnetic resonance imaging is now the radiological procedure of choice in the preoperative assessment of patients suspected of having pituitary tumors or recurrences, because, in addition to depicting the tumor, it defines the arterial anatomy and excludes all but very small coexistent aneurysms. PMID- 1584360 TI - Oculomotor nerve repair using interposed nerve graft. AB - A case of interposed nerve graft repair of an oculomotor nerve damaged during surgery for a laterally growing retrosellar pituitary adenoma is reported. The patient showed partial but functionally useful recovery of nerve function and was able to resume professional work. Only a few reports of end-to-end repair have been published, and they indicate that partial return of nerve function can be expected in such cases. PMID- 1584361 TI - Spontaneous disappearance of a huge cerebral arteriovenous malformation: case report. AB - A case of spontaneous disappearance of a cerebral arteriovenous malformation (AVM) is reported. A 59-year-old woman, who had been diagnosed as having a huge AVM in the left occipital lobe 6 years before and who was monitored without treatment, complained of a sudden headache and vomiting. Computed tomography revealed an acute subdural hematoma, intracerebral hematoma, and subarachnoid hemorrhage, for which a craniotomy was performed. Cerebral angiograms performed 9 days after the operation demonstrated a decrease in the size of the AVM. Repeated cerebral angiograms performed a month later demonstrated complete disappearance of the AVM. Follow-up angiograms performed 19 months after hemorrhage confirmed complete disappearance of the AVM. Spontaneous disappearance is known to occur occasionally in small AVMs but rarely in huge ones such as the one presented here. Several possible mechanisms for spontaneous disappearance of AVMs are discussed. PMID- 1584362 TI - Systemic multiple aneurysms of the extracranial internal carotid artery, intracranial vertebral artery, and visceral arteries: case report. AB - A rare case of systemic multiple aneurysms located in the extracranial internal carotid artery, intracranial vertebral artery, and intraperitonial arteries is described. A 56-year-old woman was referred to our hospital with suspected rupture of an aneurysm of the right extracranial internal carotid artery. Digital subtraction angiography demonstrated a giant aneurysm in the right extracranial internal carotid artery and an aneurysm of fusiform type of the left intracranial vertebral artery. The extracranial carotid artery aneurysm was successfully resected, with end-to-end anastomosis of the internal carotid artery, preserving the cranial nerves. Five days later, an aneurysm of the left hepatic artery ruptured unexpectedly and was treated with emergency surgery. Other aneurysms in the liver and spleen were identified on postoperative celiac angiography. The patient subsequently underwent an operation for a left intracranial vertebral artery aneurysm by proximal clipping. PMID- 1584363 TI - Ruptured occult arteriovenous malformation associated with an unruptured intracranial aneurysm: report of three cases. AB - Three patients who were admitted for intracranial hemorrhage are reported. Cerebral angiography demonstrated an aneurysm arising from the middle cerebral artery bifurcation. No other malformation was visible either on the computed tomographic scan or on angiography. The diagnosis was ruptured middle cerebral artery aneurysm with intracerebral hematoma. At surgery, there was no blood in the sylvian fissure and the aneurysm was not ruptured. Evacuation of the hematoma and thorough exploration of the cavity led to the discovery and resection of a small vascular anomaly typical of an arteriovenous malformation responsible for the hemorrhage. Occult vascular malformations and the association of aneurysm with arteriovenous malformations are discussed. In these 3 patients, the coexistence of these two malformations could be related to a common congenital abnormality. PMID- 1584364 TI - Enlarging endostoma (bone island) of the spinous process. AB - Endostoma of bone (bone island) is a rare lesion and has been described in the spinous process in only one previous publication. Although these lesions are benign, they have a potential for enlargement. Radiography cannot completely differentiate these lesions from more aggressive processes, and removal of the lesion should be considered. PMID- 1584365 TI - Limitations of angiographic target localization in planning radiosurgical treatment. AB - Planning radiosurgical treatment for cerebral arteriovenous malformations requires accurate definition of the true tridimensional size and shape of the nidus. Over- or underestimation of these parameters may result in undue irradiation of normal brain tissue or suboptimal irradiation coverage of the malformation leading to treatment failure. Angiography is not an ideal database for radiosurgery of arteriovenous malformations. Its shortcomings include planar representation of a tridimensional volume and simultaneous visualization of feeding arteries and draining veins overlapping with the nidus and obscuring its outline. Two illustrative clinical cases of these angiographic inadequacies are presented. Stereotactic, contrast-enhanced computed tomography may provide, in selected cases, better spatial definition of the nidus and superior anatomic detail for the final design of the radiosurgical isodose distribution. PMID- 1584366 TI - Unusual delayed radial nerve palsy caused by a traumatic aneurysm of a collateral radial artery: report of two cases. AB - Two patients with delayed radial nerve palsy occurring a month after penetrating missile wounds are presented. The history and presence of a pulsatile mass over the posterolateral aspect of the arm were highly suggestive of a traumatic aneurysm of a collateral radial artery, confirmed by angiography in one patient and at surgery in the other. After removal of the aneurysm and radial nerve neurolysis, the patients' symptoms were relieved. In a thorough review of the literature, we found these to be the first examples of traumatic aneurysms of collateral radial arteries causing unusual delayed neural palsies. PMID- 1584368 TI - A new way to monitor external ventricular drainage. AB - External ventricular drainage is prone to mechanical complications and monitoring the system is not easy. It requires repeated checking of the drip or the level of the drained cerebrospinal fluid (CSF) in the bag. It was thus proposed that an efficient method by which to monitor the complete external ventricular drainage system would be by continuously weighing the drained CSF. Using weighing scales, a converter, and a recorder, the CSF weight was displayed as a function of time (i.e., flow, if the specific gravity of the CSF is 1, which is usually the case as an approximation). This system was used in 16 comatose patients (11 with subarachnoid hemorrhages and 5 with hydrocephaly during 204 recorded periods of 22.7 +/- 2.8 hours (mean +/- standard deviation). The mean flow was 0.17 +/- 0.05 ml/min. A cessation of CSF flow was seen graphically as a plateau. This occurred 18 times because of obstruction, which was relieved before clinical worsening by making minor adjustments in 15 patients and by reinsertion of a drain in 3 patients. Nociceptive stimuli like tracheal suctioning were also clearly visible on the graph (increased slope, i.e., increased CSF flow). This type of external ventricular drainage monitoring appears to be safe and reliable, giving indications before changes in medical condition. The observed flow, however, is not equal to its rate of secretion but rather to the difference between CSF secretion and reabsorption. PMID- 1584367 TI - Intraventricular vancomycin-induced cerebrospinal fluid eosinophilia: report of two patients. AB - Pediatric neurosurgeons commonly instill vancomycin into the ventricles to treat shunt infections. This use for vancomycin, however, has not been studied in the laboratory to evaluate possible toxicities and side effects. We report two cases of cerebrospinal fluid eosinophilia (CSFE) secondary to the intraventricular administration of vancomycin. Two other cases of shunt infection during the same time period were treated for only 2 days with intraventricular vancomycin and did not manifest CSFE. We address the clinical problems and possible detrimental effects of CSFE in the setting of shunt infection. We propose a mechanism of vancomycin-induced mast cell degranulation and subsequent release of eosinophil chemotactic factor as a cause of CSFE. An initial dose of intraventricular vancomycin should take into account volume of distribution (ventricular size) to obtain a peak cerebrospinal fluid concentration of 20 to 30 micrograms/mL. We recommend following daily cell counts and vancomycin peak and trough levels to calculate the amount and frequency of intraventricular vancomycin required to maintain safe and effective concentrations and to monitor for CSFE. PMID- 1584369 TI - Medical manpower needs at home and abroad. AB - Medical manpower is ordinarily expressed as a ratio of the number of physicians (e.g., neurosurgeons) to the population of the geographic area (e.g., country). The many other factors that go into assessing medical manpower needs and the manner in which those factors may vary from one country to another and from one time to another are described. Despite the paucity of physicians in some countries and in some parts of the world, there is a suplus of physicians worldwide. PMID- 1584370 TI - Development of human neural transplantation. PMID- 1584371 TI - Cerebral arteriovenous malformations: factors influencing the surgical difficulty and outcome. PMID- 1584373 TI - Spontaneous spinal subdural hematoma: case report and review of the literature. PMID- 1584372 TI - Clinical clerkships in neurosurgery and neurology at United States medical schools. PMID- 1584374 TI - Facet fracture-dislocation injuries of the cervical spine. AB - Sixty-eight patients with acute traumatic cervical facet fracture-dislocation injuries are presented. These patients represented 6.7% of all cervical spine fractures identified over a 12-year period. Thirty-one patients had unilateral facet injuries and 37 had bilateral facet injuries. Neurological morbidity was 90% and was most severe among bilateral facet injury patients (84% complete injuries). Spinal shock was identified in 13 patients and was a poor prognostic indicator for the subsequent recovery of associated neurological deficits. Closed reduction was attempted in 66 of 68 patients and was successful in 58% of the patients. Seven patients deteriorated. Open reduction-internal fixation was successful in 83% of 24 patients with a 4% morbidity. Seventy-eight percent of patients improved with rapid closed reduction, and 60% improved with open reduction-internal fixation; however, only 10 patients of the entire 68 made significant neurological recoveries. In these 10 patients, the timing of decompression-realignment appeared to be more important than the means of reduction. PMID- 1584375 TI - Management of thoracolumbar fractures with accompanying neurological injury. AB - The optimal surgical approach for spinal canal reconstruction of thoracolumbar fractures is controversial, and the relationship between spinal canal reconstruction and neurological recovery remains unclear. To address these issues, 22 consecutive cases of thoracolumbar fracture with accompanying neurological deficit were reviewed. Neurological status was graded at the time of admission, postoperatively, and at a mean of 15 months postinjury. By using preoperative and postoperative radiographs and computed tomographic scans, the degree of spinal canal compromise was quantified in the sagittal, coronal, and axial planes. All fractures were stabilized by posterior instrumentation and fusion, and in 10 injuries, retropulsed vertebral body fragments were further reduced by posterolateral decompression. Spinal canal dimensions, neurological function, and operative approach were compared by using nonparametric statistical analysis. The greater the initial spinal canal compromise, the more severe the neurological deficit (P = 0.04). With injuries involving L1 and above, this relationship increased (P = 0.003). The extent of spinal canal reconstruction failed to correlate with neurological recovery. Compared with spinal instrumentation alone, transpedicular decompression showed no benefit in terms of postoperative canal dimensions or neurological outcome. On the basis of this experience, transpedicular decompression offers no advantage over spinal instrumentation alone. The relationship between initial spinal canal encroachment and neurological deficit demonstrates that the degrees of bony and neurological injury directly reflect the kinetic energy transferred at the time of impact. The lack of correlation between the extent of spinal canal reconstruction and neurological recovery suggests that ongoing neural compression/distortion contributes little to the overall neurological injury. PMID- 1584376 TI - Lumbar surgery in the elderly. AB - By virtue of modern neuroimaging, neurosurgeons are increasingly confronted by patients once deemed too old for lumbar corrective procedures. Management of these patients is problematic, as the literature is relatively mute in regard to results and complications within this elderly cohort. We, therefore, reviewed all surgical procedures for benign lumbar disease at two large metropolitan hospitals from January 1986 to June 1988 for patients greater than or equal to 70 years of age. There were 155 procedures performed on 143 patients (male:female, 48:95); the average age of the patients was 74.9 +/- 8.8 years; there were 32 cases of herniated disc, 29 cases of disc plus hypertrophic ligament/bone, and 94 cases of lateral recess/stenosis alone. Hospital stay averaged 7.5 +/- 3.5 days, and increasing age did not correlate with an extended admission. Major morbidity was low (6.9%), and there were no deaths. At follow-up, an average of 34.3 +/- 12.2 months postoperatively, 66.6% (56 of 84) of the patients reported no or minimal discomfort, whereas 15.4% (13 of 84) had not improved at all. Overall, 77.3% (65/84) were pleased with their procedure. These data represent the most comprehensive review in the literature of lumbar procedures in the elderly and indicate that these operations may be undertaken in this population with acceptable morbidity and a reasonable expectation of clinical improvement. PMID- 1584377 TI - Primary spinal epidural non-Hodgkin's lymphoma: report of eight patients and review of the literature. AB - Eight patients treated for histologically confirmed primary spinal epidural non Hodgkin's lymphoma diagnosed between January 1979 and August 1989 (6.6% of all cases of intraspinal lymphoma) were studied. There were six men and two women. The median age was 70 years (range, 43-80 yr). Patients sought treatment for a prodrome of back pain (median duration, 3 mo) followed by an acute neurological deterioration (median duration, 6 d). The most common findings were a discrete sensory level in 5 patients, hyperreflexia in 5 patients, and paraparesis or paraplegia in 5 patients. Radiographically, there was an absence of bony destruction by these tumors. All patients underwent a decompressive laminectomy, subtotal tumor resection, and spinal irradiation (median dose, 3800 cGy). Two patients had low-grade lymphomas (one B cell and one T cell), and 6 patients had intermediate-grade lesions (six B cell). Two patients with B-cell lymphomas (one low-grade and one intermediate-grade) developed metastatic disease 15 and 17 months after the initial diagnosis; no evidence of lymphoma developed in the other 6 patients. The median survival was 22 months (range, 2-71 mo). Lymphoma was the cause of death in only 1 of the 4 patients who died, and the 4 younger patients are alive and well. Primary spinal epidural non-Hodgkin's lymphoma should be a diagnostic consideration in the older patient who seeks treatment for spinal cord compression manifested by a prodrome of back pain, followed by a rapid neurological deterioration, normal plain spine radiographs, and neuroimaging consistent with an extradural compressive lesion. Surgery for this diagnosis followed by spinal irradiation should result in significant neurological improvement. PMID- 1584378 TI - Traumatic extradural hematoma of delayed onset is not a rarity. AB - During a 4.5-year period, 73 patients with traumatic extradural hematoma (EDH) were admitted to the neurosurgical unit of the same hospital and managed with surgical evacuation. Of these consecutive admissions, 22 patients with delayed EDH are reported. The incidence of this condition (30%; 22 of 73) contrasts with reports in the literature of 0 to 10%. This may be related to the availability of computed tomography and its liberal and early use in all head injuries. The overall mortality of traumatic EDH (5%; 4 of 73) was related to cases of delayed onset EDH. In addition to a high index of suspicion, early diagnosis of delayed EDH can be facilitated by liberal use of intracranial pressure monitoring and serial computed tomography. PMID- 1584379 TI - Neuropsychological deficits in patients with persistent symptoms six months after mild head injury. AB - There is much debate on the nature and duration of cognitive deficits and postconcussive symptoms (PCS) after mild head injury. Most studies performed so far have compared head-injured patients with subjects who had not suffered a concussion, instead of directly comparing patients with and without persistent PCS. The present study examined whether patients with PCS (n = 9) about 6 months after an uncomplicated mild head injury performed less well on selected neuropsychological tests than patients with mild head injuries who did not have PCS (n = 9) and healthy controls (n = 9). Patients with PCS were individually matched with controls for the time elapsed after the injury, age, sex, and education. We found that patients with PCS performed less well on tests of divided and selective attention than both patients without PCS and healthy controls. It is concluded that cognitive deficits may be present up to 6 months after mild head injury when symptoms persist. The findings indicate that patients with mild head injury and subjective symptoms may manifest demonstrable cognitive deficits. PMID- 1584380 TI - The significance of posttraumatic increase in cerebral blood flow velocity: a transcranial Doppler ultrasound study. AB - Using transcranial doppler ultrasonography, cerebral blood flow velocity was measured daily from both middle cerebral arteries in 121 patients who had suffered minor (n = 55), moderate (n = 16), or severe (n = 50) brain injury. Serial computed tomographic scans were performed to identify noncontusion-related infarction (NCI). Cerebral perfusion pressure was monitored continuously in 41 patients who had severe head injury; of these, 22 had continuous measurement of arterial and jugular bulb venous oxygen (SJO2) saturation. Abnormally high mean flow velocity (greater than 100 cm/s) was observed in 23 patients (minor injury, n = 3; moderate injury, n = 3; severe injury, n = 17), but was recorded only when cerebral perfusion pressure exceeded 60 mm Hg (P less than 0.0001). Fourteen patients who underwent SJO2 monitoring developed increased mean flow velocity (MFV). In 6, the arterial-jugular venous oxygen content difference (AVDO2) was below 4 ml/dl, indicating global cerebral hyperemia. All had bilateral elevation of MFV, and 6 of the 8 nonhyperemic patients (AVDO2, 4-9 ml/dl) had a unilateral increase of MFV (P = 0.018). Four of the 23 patients with increased MFV developed NCI, as compared with none of the patients without elevated MFV (P = 0.015). All patients with NCI had suffered severe brain injury, had unilateral elevation of MFV in the terriory of the relevant cerebral vessel, and had received therapy to correct reduced cerebral perfusion pressure (P = 0.008). NCI did not occur in any patient with increased MFV that was associated with global hyperemia. PMID- 1584381 TI - Significance of periventricular hemodynamics in normal pressure hydrocephalus. AB - To delineate the pathophysiology of periventricular hemodynamics in normal pressure hydrocephalus, we performed quantitative and three-dimensional measurements of cerebral blood flow (CBF) by using xenon-enhanced computed tomographic scans. Measurements were made on 7 patients in whom normal pressure hydrocephalus after subarachnoid hemorrhage had been confirmed by clinical improvement after shunting. We compared mean CBF values in the white matter and cortex of the frontal, temporal, parietal, and occipital lobes and in the thalamus before and after shunting, with an evaluation of dementia and the extent of ventricular dilation and periventricular lucency on computed tomographic scans. CBF returned to within normal limits in the white matter of the frontal and temporoparieto-occipital lobes. CBF restoration closely correlated with clinical improvement and reduction in ventricular dilation and periventricular lucency. We speculate that ischemia occurs initially in the periventricular white matter as a result of diffused cerebrospinal fluid and then extends of the cortex and to the thalamus, causing a "misery perfusion" state with neuronal dysfunction. Incomplete improvement of dementia and CBF in the cortex and thalamus may be explained by preexisting arteriosclerosis in aged patients, coexisting brain damage caused by subarachnoid hemorrhage and subsequent surgical insult in aneurysm patients, and delayed recovery of cortical function that has been secondarily impaired by the periventricular lesions. PMID- 1584382 TI - Complications of ventriculoperitoneal shunt procedures or hydrocephalus associated with vein of Galen malformations in childhood. AB - Twenty children with vein of Galen malformations and hydrocephalus required a ventriculoperitoneal shunt. Shunt placement was associated with a 70% incidence of complications that included status epilepticus in 3 patients, intraventricular hemorrhage in 7 patients, and subdural hematoma or hygroma in 5 patients. Based upon this experience, the authors recommend the use of preoperative prophylactic anticonvulsants and the placement of medium pressure frontal ventriculoperitoneal shunts. This report will address the overall experience with and the basis on which these therapeutic recommendations were made. PMID- 1584383 TI - Neurogenic dysphagia resulting from Chiari malformations. AB - Between 1980 and 1989, 15 of 46 patients (11 children, 4 adults) who underwent suboccipital craniectomy and cervical laminectomy for symptomatic Chiari malformations presented with manifestations of neurogenic dysphagia. Each of these patients had normal swallowing function before the development of dysphagic symptoms. Dysphagia was progressive in all 15 and, in most cases, preceded the onset of other severe brain stem signs. The rate of symptom progression varied depending on the age of the patient. Whereas the six infants (all Chiari II) deteriorated rapidly after the onset of initial symptoms, the five older children (two Chiari I, three Chiari II) and four adults (all Chiari I) showed a more gradual deterioration. In 11 patients with severe dysphagia, barium video esophagograms, pharyngoesophageal motility studies, continuous esophageal pH monitoring, and appropriate scintigraphic studies were useful in defining the scope of the swallowing impairment and determining whether perioperative nasogastric or gastrostomy feedings, gastric fundoplication, and/or tracheostomy were needed to maintain adequate nutrition and avoid aspiration. These patients all had widespread dysfunction of the swallowing mechanism, with a combination of diffuse pharyngoesophageal dysmotility, cricopharyngeal achalasia, nasal regurgitation, tracheal aspiration, and gastroesophageal reflux. The pathophysiology of these swallowing impairments and their relation to the hindbrain malformation is discussed. Postoperative outcome with regard to swallowing function correlated with the severity of preoperative symptoms. The four patients with mild dysphagia showed rapid improvement in swallowing function after surgery. Seven patients with more severe impairment but without other signs of severe brain stem compromise, such as central apnea or complete bilateral vocal cord paralysis, also improved, albeit more slowly. In contrast, the outcome in the four patients who developed other signs of severe brain stem dysfunction before surgery was poor. Early recognition of neurogenic dysphagia and expeditious intervention are therefore crucial in ensuring a favorable neurological outcome. PMID- 1584384 TI - The cerebral radioprotective effect of alternative barbiturates to pentobarbital. AB - The potential for normal brain tissue injury is one of the limiting factors in the use of radiotherapy for brain tumors. As attempts to enhance brain tumor radiation sensitivity have been unsuccessful, the use of cerebral radioprotectants provides an attractive alternative. Pentobarbital has recently been shown to be a cerebral radioprotectant in the rodent and primate models of single fraction radiation injury. Because daily high doses of pentobarbital bring certain significant risks, the potential usefulness of alternative barbiturates was explored. Seven groups of rats received 70 Gy of whole-brain-only irradiation in the single fraction. Group 1 was treated while awake. Groups 2, 3, and 4 received pentobarbital, thiopental, and methohexital, respectively. Groups 5, 6, and 7 received increasing doses of phenobarbital. Mean group survival at 30 days after treatment was determined and compared with the survival of animals treated while awake. Thiopental enhanced survival, similar to pentobarbital. Methohexital and phenobarbital were of no radioprotective value. The differences in the hypnotic effects of these barbiturates is based on dissimilar effects on the kinetics of chloride ion channel patency. We propose that these differences also influence their radioprotective properties. Thiopental is a shorter acting alternative to pentobarbital for cerebral radioprotection. Use of it should permit safer and easier investigation of this radioprotective effect in human trials. PMID- 1584385 TI - Ipsilateral pallidal control on the sternocleidomastoid muscle in cats: relationship to the side of thalamotomy for torticollis. AB - To elucidate the role of the basal ganglia on neck movement control and thus clarify the side of targets for stereotactic surgery of spasmodic torticollis, effects of electrical stimulation to the globus pallidus-entopeduncular nucleus complex (GP-EP) upon the activities of the sternocleidomastoid (SCM) muscle motoneurons were studied in cats. Repetitive stimulation of the ipsilateral GP-EP increased discharge rate in the majority of the SCM motoneurons, whereas contralateral GP-EP stimulation caused a decrease in discharge rate. These effects were gradually enhanced in the course of repetitive stimulation and lasted even after its cessation. Bilateral ablation of the motor and premotor cortices did not influence the effects of GP-EP stimulation. Latency studies suggested that the pallidal control of the SCM motoneuron is mediated by polysynaptic pathways on both sides; however, these same studies produced evidence of an ipsilateral oligosynaptic connection, as well. Repetitive antidromic stimulation of the accessory nerve caused a gradual increase in discharge rate of the SCM motoneurons, similar to the augmentation induced by ipsilateral GP-EP stimulation. Features of the responses indicate that the pallidal control on the neck muscles involves reverberating circuits in the brain stem and spinal cord. These experimental findings suggest that stereotactic thalamotomy of the ventrolateral nucleus for spasmodic torticollis should be performed on the side ipsilateral to the contracting SCM muscle. PMID- 1584386 TI - Direct vein graft reconstruction of the cavernous, petrous, and upper cervical internal carotid artery: lessons learned from 30 cases. AB - The authors report a series of 30 patients who underwent reconstruction of the internal carotid artery (ICA) at the skull base with the saphenous vein during the surgical management of lesions at the cranial base. This group represents about 9% of the total patients in whom the ICA in the cavernous or petrous segment was manipulated either during the surgical approach or dissection from the tumor. Two of these patients failed a clinical balloon test occlusion of the ICA, and, in 9 patients, cerebral blood flow during balloon test occlusion dropped to between 15 to 30 ml/100g/min. The patency rate is 86% over a mean follow-up time of 18 months. Of the 4 patients with graft occlusion, 3 were asymptomatic. The fourth patient who suffered ICA dissection with graft occlusion subsequently died from a massive cerebral infarction. Three patients with inadequate collateral circulation sustained minor strokes as the result of the temporary ICA occlusion during the grafting, but all are capable of leading independent lives. Two patients suffered acute graft occlusion within 12 hours of the surgery and underwent successful revision of the graft. None of the grafted patients suffered delayed occlusion or ischemic or embolic problems. The patients with malignant tumors died within 2 years of the operation from the original disease; total tumor removal was accomplished in 14 of the 19 patients with benign tumors. The aneurysms were successfully eliminated in all 5 patients. The lessons learned from this experience are discussed. PMID- 1584387 TI - Subperiosteal subtemporal approach: technique and applications. AB - The authors describe a craniofacial surgical approach that they have used since 1987. Based on existing anatomical continuity between the subtemporal plane and the cranial periosteum, it consists of a direct subperiosteal subtemporal cleavage. Preservation of continuity between the muscle and the periosteum allows the operator to return the temporalis muscle to a normal position at the end of the operation when the scalp is sutured. This approach avoids superficial cleaving of the temporalis muscle or section and reinsertion to the fronto orbital rim. It also allows access to the upper third of the face without jeopardizing the frontal ramus of the facial nerve. PMID- 1584388 TI - Ventriculoatrial shunt distal catheter placement using transesophageal echocardiography: technical note. AB - Accurate placement of the distal end of a ventriculoatrial shunt at the cavo atrial junction is important for long-term shunt function as well as for avoiding cardiac arrhythmias, thrombus formation, and damage to myocardial tissue. Standard methods of intraoperative localization, including chest x-ray, pressure measurements, and electrocardiogram recording, can be inaccurate. By using intraoperative transesophageal echocardiography, the distal end of the catheter can be localized to the cavo-atrial junction. PMID- 1584389 TI - Neurological surgery in the nineteenth century: the principles and techniques of Ernst von Bergmann. AB - Born in Latvia in 1836, Ernst von Bergmann received his medical education and first academic position at the University of Dorpat in Russia. In 1866, he served as a military surgeon in the Prusso-Austrian War, followed by duty in the Franco Prussian War of 1870. He was appointed to the faculty of the University of Wurzburg in 1878 and 4 years later moved to the University Clinic in Berlin. As a professor and chairman of surgery, he taught until his death in 1907. Von Bergmann practiced general surgery but devoted a large part of his career to the treatment of neurological diseases. Known for his development of aseptic technique, his early military experiences directed his attention to cranial trauma and, ultimately, neurosurgery. In 1880, he authored his first textbook, which described missile ballistics and animal experiments first demonstrating the physiological response later known as "the Cushing reflex" and advocated meticulous intracranial debridement with thorough closure after trauma. Twenty years later, as senior editor of the massive System of Practical Surgery, his contributions included pediatric neurosurgery, successful treatment of abscesses and tumors, diagnostic radiography, and cerebral localization using external landmarks and the neurological examination. Revered by his students and honored by his colleagues, von Bergmann became a proponent for aggressive neurosurgical treatment. His skilled techniques, developed in parallel with accurate experimental physiology, advanced 19th century surgical progression and formed a solid framework for the advances of neurosurgical specialists. PMID- 1584390 TI - Chiari I malformation with traumatic syringomyelia and spontaneous resolution: case report and literature review. AB - A case history of a 28-year-old woman who sustained a moderately severe head injury and then developed acute bilateral arm weakness is presented. Magnetic resonance imaging studies revealed a Chiari I malformation with a large cervical syringomyelia (hydromyelia). The patient's arm weakness almost completely resolved spontaneously as did her syrinx. How this case is interpreted in light of the various theories of pathogenesis will be discussed. PMID- 1584391 TI - Caspar plate fixation for the treatment of complex hangman's fractures. AB - This report details our recent experience with the surgical treatment of complex hangman's fractures after failure of closed reduction and immobilization in external orthosis. We have successfully treated hangman's fractures in 5 patients with anterior Caspar plate stabilization and C2-C3 interbody fusion. The specific anatomical features of these fractures were complex, rendering the spines of the patients highly unstable. The patients were considered surgical candidates when reduction could not be achieved or maintained with axial traction or halo immobilization. Each patient underwent anterior C2-C3 interbody bone fusion and Caspar plating from C2 to C3. All patients achieved adequate intraoperative reduction and were immobilized postoperatively with a halo vest. The follow-up period ranged from 3 to 28 months and provided a 100% fusion rate with no complications related to plating or nonunion. Our initial experience indicates that anterior C2-C3 interbody bone fusion and Caspar plate fixation is a suitable treatment option for patients with complex hangman's fractures who are not successfully managed nonoperatively. PMID- 1584392 TI - Endoscopic cure of a giant sacral meningocele associated with Marfan's syndrome: case report. AB - An unusual anterior sacral meningocele associated with Marfan's syndrome, with demonstrated dural anomalies related to Marfan's syndrome is reported. Endoscopy enabled complete exploration of the meningocele, its morphological description, and ultimate cure. The meningocele resembled an hourglass made up of intrasacral and anterior sacral components. The communication of this bilobed malformation with the dural sac was so small that only the intrathecal injection of a colored solution allowed its localization. The closure of this communication was accomplished under endoscopic view by a single stitch. The postoperative course of the patient was characterized by immediate disappearance of the preoperative clinical signs. Computed tomographic scans demonstrated progressive complete collapse of the anterior sacral meningocele and partial resolution of the intrasacral component. Dural anomalies of Marfan's syndrome are described, and their relationship to the formation of the meningocele is discussed. PMID- 1584393 TI - Lyme neuroborreliosis manifesting as an intracranial mass lesion. AB - Lyme neuroborreliosis is one of the chronic manifestations of Lyme disease and is caused by the neurotropic spirochete, Borrelia burgdorferi. Two of the three stages of Lyme disease potentially involve the central nervous system: a second stage that may manifest as meningitis, cranial neuritis, or radiculoneuritis; and a third stage, or chronic neuroborreliosis, with parenchymal involvement. The tertiary stage may mimic many conditions, including multiple sclerosis, polyneuropathy, viral encephalitis, brain tumor, vasculitis, encephalopathy, psychiatric illness, and myelopathy. We report a 10-year-old child with signs, symptoms, and radiological manifestations of intracranial mass lesions, without previously recognized manifestations of Lyme disease. This proved to be Lyme neuroborreliosis, documented by histological and serological examination, which responded well to antibiotic therapy. The need to establish a tissue diagnosis of intracranial mass lesions is emphasized, and the utility of a computed tomographic-guided stereotactic system for this purpose is discussed. PMID- 1584394 TI - Leigh's disease presenting as an intramedullary mass lesion. AB - An unusual presentation of Leigh's disease consisting of rapid progression of leg weakness in a young child is discussed. Magnetic resonance imaging revealed an intramedullary mass lesion of the conus medullaris. Surgical exploration revealed only necrosis and inflammation. Subsequent studies revealed pathology in the cerebrum as well as the spinal cord. Metabolic abnormalities confirmed the diagnosis of Leigh's disease. The differential diagnosis of intramedullary mass lesions demonstrated by magnetic resonance imaging should include metabolic, inflammatory, and ischemic processes as well as neoplastic disease. PMID- 1584395 TI - Intraosseous hematoma of the skull: case report. PMID- 1584396 TI - Multifocal cavernous hemangioma of the skull: report of a case and review of the literature. AB - Primary hemangiomas, which are rare skeletal tumors, represent 0.7% of all osseous neoplasms. They are most commonly found in the vertebral column. They are exceedingly rare in the calvarium, accounting for 0.2% of all bone neoplasms. Most calvarial lesions are unifocal, but multiple hemangiomas have been reported. We present the case history of a 64-year-old man who was admitted with frontal and occipital headaches. He was found to have two radiolucent lesions on plain x ray, left frontal and left occipital, which proved to be cavernous hemangiomas. The gross appearance, histopathology, radiological findings, and treatment options are reviewed. PMID- 1584397 TI - Meningeal sarcoma with rhabdomyoblastic differentiation: case report. AB - A case of primary neoplasm of the meninges with unusual histological and clinical features, which occurred in a 61-year-old man is described. Although conventional light microscopy revealed an undifferentiated tumor consisting of small- to medium-sized elements, it did not allow any definitive histogenetic interpretation. Immunohistochemistry showed that the neoplastic cells were positive for actin, desmin, myoglobin, and vimentin, thus leading to the diagnosis of meningeal sarcoma with rhabdomyoblastic differentiation. This interpretation was also supported by electron microscopy, in dewaxed tissue samples, which revealed the presence of abortive Z-lines. It is noteworthy that retrospective microscopic examination of all the slides obtained both at initial presentation and at relapses demonstrated in some fields that the undifferentiated population was associated with typical meningiomatous features, as was also shown by the staining for the epithelial membrane antigen. Clinically, the tumor was characterized by an exceedingly long course (10 years). The histogenesis of the tumor and the diagnostic relevance of immunohistochemical techniques are discussed. PMID- 1584398 TI - Primary intrasellar germinoma: case report. AB - Intracranial germinomas arising primarily within the sella turcica are extremely rare. Preoperative diagnosis is difficult to establish even with sophisticated procedures. Diabetes insipidus is the main clinical manifestation. The authors report a case of an apparently primary intrasellar germinoma causing subclinical pituitary apoplexy in a 12-year-old boy. The transsphenoidal approach and appropriate radiotherapeutic management were employed with a good outcome. PMID- 1584399 TI - Meningioma of the falcotentorial region: report of two cases and literature review of occlusion of the galenic system. AB - Two patients with verified meningiomas involving the posterior part of the falx and the midline tentorium extending into the pineal region are reported. Preoperative angiography disclosed occlusion of the straight sinus in both patients. The operative results are described, and the safety of surgical occlusion of the galenic system is discussed. PMID- 1584400 TI - A large aneurysm of the persistent primitive hypoglossal artery. AB - An aneurysm of a persistent primitive hypoglossal artery (PHA) particularly at its junction with the basilar artery, often poses therapeutic problems. This is attributable not only to the size and location of the aneurysm but also to the fact that the persistent PHA is functionally the single artery providing blood in posterior circulation. We report a 31-year-old man with a large aneurysm of the persistent PHA at its junction with the basilar artery and review the existing literature. We clipped the broad neck of the aneurysm through a lateral suboccipital craniectomy; however, the patient suffered a second episode of subarachnoid hemorrhage. Angiography disclosed a slipped clip incompletely obstructing the persistent PHA. He received no further treatment for the aneurysm because of his deteriorating condition. Direct surgical treatment, although it failed to obliterate the aneurysm neck in our patient, should be recommended for a persistent PHA aneurysm. PMID- 1584401 TI - Acquired mirror-image cerebellopontine angle arachnoid cysts: case report. AB - Arachnoid cysts are neurosurgical entities that have long been considered to be congenital in origin. Many examples in the literature suggest that there is a subgroup of arachnoid cysts that are required. The authors present the clinical history of a 17-month-old girl who developed two cerebellopontine angle arachnoid cysts after posterior fossa surgery for a brain tumor. After surgical excision of the tumor the child developed a left cerebellopontine angle cyst. This was treated through a suboccipital craniectomy by evacuating the cyst and excising the cyst wall. Two months later the child developed a second right-sided cerebellopontine angle cyst. It was treated by inserting a cystoperitoneal shunt. This article presents the case with radiological evidence of the acquired nature of the cysts. It also includes a brief review of the clinical presentation, pathogenesis, radiological evaluation, and surgical treatment of arachnoid cysts with emphasis on those occurring in the posterior fossa. PMID- 1584402 TI - Effect of etomidate on motor evoked potentials in monkeys. PMID- 1584403 TI - Use of intrathecally administered morphine in the treatment of postoperative pain after lumbar spinal surgery: a prospective, double-blind, placebo-controlled study. PMID- 1584404 TI - Development of human neural transplantation. PMID- 1584405 TI - Elevated cortical venous pressure in hydrocephalus. PMID- 1584406 TI - The integrative properties of spiny distal dendrites. AB - The dendritic spines of many central neurons are generally thought to modulate the ability of individual synaptic conductances to depolarize the dendritic shaft. A compartmental analysis using typical spine dimensions shows that spine neck resistances are probably far too low to support such a function, because low conductance synapses act as time-varying current sources. However, the collective presence of all spines on a dendrite significantly modifies the electrical properties of the branch in ways which have previously been overlooked. In particular, they lower its input impedance and length constant, reducing the amplitude of the unitary excitatory postsynaptic potential as well as the strength of spatial summation. This enables a dendrite to integrate large numbers of synaptic inputs while occupying minimal volume. In this way, dendritic spines are analogous to axonal myelin, which also alters transcellular impedance in order to maximize neurite function and minimize volume. Unlike membrane resistance changes, spines have little effect on the membrane time-constant so they maintain a long window for temporal summation. Though spine shape and neck resistance do not significantly affect dendritic potentials, spine area does. Therefore, while changes in spine morphology probably do not directly potentiate the strength of individual synapses, changes in spine density can regulate the synaptic excitability of an entire dendrite. The shortened length-constant of the spiny dendrite requires excitable membranes to be located in distal dendrites. These, in turn, eliminate many of the electrotonic nonlinearities associated with summation in long, thin processes, and make all distal synapses equipotent. The short length-constant also enhances the sensitivity of dendritic spikes to local impedance changes while decreasing the sensitivity to distant impedance changes. This would enable a neuron to effectively use inhibitory synapses or branch points to regulate propagation through its spiny dendritic tree. A model neuron is developed in which dendritic spines, excitable membranes, and dendritic branching combine to form a two-stage filter, which serves as a synaptic input coincidence detector with adjustable gain. Gain is regulated by potassium conductances which modulate branch point safety factor. The model is consistent with the notion of functional independence of distal dendrites and demonstrates that certain aspects of dendritic spiking which have previously been thought to require membrane hot-spots can also result from geometrical properties. It is suggested that the activation of spiny neurons may depend as much on the density as on the number of active synapses, and that spiny neurons may tend to have discrete output states whereas nonspiny neurons may be more continuous. PMID- 1584407 TI - Serotonergic fibers induce a long-lasting inhibition of monosynaptic reflex in the neonatal rat spinal cord. AB - The transmitter mechanism of a long-lasting descending inhibition of the monosynaptic reflex was investigated in the isolated spinal cord of the neonatal rat. The monosynaptic reflex elicited by dorsal root stimulation was recorded extracellularly from a lumbar ventral root (L3-L5). Electrical stimulation of the upper thoracic part of the hemisected cord caused an inhibition lasting about 40 s of the monosynaptic reflex. This descending inhibition was markedly attenuated by perfusing the spinal cord with reserpine (1 microM) or 5,7-dihydroxytryptamine (10 microM) for 2-6 h. The perfusion with reserpine (1 microM) for 4 h significantly decreased the contents of 5-hydroxytryptamine, dopamine, and norepinephrine of the neonatal rat spinal cord, whereas the perfusion with 5,7 dihydroxytryptamine (10 microM) for 4 h decreased the contents of 5 hydroxytryptamine and dopamine. The descending inhibition was markedly potentiated by a 5-hydroxytryptamine uptake blocker, citalopram (10 nM), and was blocked by a 5-hydroxytryptamine antagonist, ketanserin (10-100 nM). Application of 5-hydroxytryptamine to the spinal cord induced an inhibition of the monosynaptic reflex, a later part of which was blocked by ketanserin. Ketanserin also moderately blocked inhibitions of the monosynaptic reflex caused by norepinephrine and dopamine. Phentolamine (10 microM) abolished the depressant actions of norepinephrine and dopamine, but did not affect that of 5 hydroxytryptamine or the descending inhibition. These results strongly suggest the involvement of 5-hydroxytryptamine, but not dopamine nor norepinephrine, in the descending inhibition. Besides ketanserin, the descending inhibition was blocked by ritanserin, haloperidol, and pipamperone, which have affinities to 5 hydroxytryptamine2 receptors, and also by spiperone and methiothepin, which are antagonists at both 5-hydroxytryptamine1 and 5-hydroxytryptamine2 receptors (all 1 microM). On the other hand, a 5-hydroxytryptamine1C and 5-hydroxytryptamine2 antagonist, mesulergine (1 microM), and 5-hydroxytryptamine3 antagonists, ICS 205 930 and quipazine (both 1 microM), did not depress either the descending inhibition or the 5-hydroxytryptamine-evoked inhibition of the monosynaptic reflex. The results with these antagonists favor the involvement of 5 hydroxytryptamine2 receptors although the results with mesulergine disagree with this notion. 5-Hydroxytryptamine1 agonists, such as 8-hydroxy-2-(di-n propylamino)tetralin, buspirone, and 5-carboxyamidotryptamine, and a 5 hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine, induced a long-lasting inhibition of the monosynaptic reflex, which was blocked by ketanserin whereas a 5-hydroxytryptamine2 agonist, S-(+)-alpha-methyl-5-hydroxytryptamine, evoked a biphasic inhibition, in which only the later component was blocked by ketanserin.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1584408 TI - Serotonin and L-norepinephrine as mediators of altered excitability in neonatal rat motoneurons studied in vitro. AB - The actions of serotonin on the membrane properties of motoneurons and on the synaptic responses evoked by stimulating the segmental dorsal root have been investigated using intracellular recording in a neonatal rat hemisected spinal cord preparation in vitro. Superfusion with serotonin produced concentration dependent depolarizations (EC50 32.1 microM) with an apparent increase in input resistance and increase in motoneuron excitability. During serotonin depolarizations an increase in membrane noise was seen. At higher serotonin concentrations repetitive firing was induced. Sensitivity to serotonin was enhanced by blockade of neuronal uptake with citalopram, when the EC50 was 1.4 microM. The depolarization was mimicked by alpha-methyl-5-hydroxytryptamine (EC50 11.7 microM). Serotonin depolarizations were blocked by ketanserin (0.1 and 1 microM), ritanserin (1 microM), spiperone (0.1 and 1 microM) and LY 53857 (1 microM). A norepinephrine-induced depolarization of motoneurons, which was mimicked by L-phenylephrine and antagonized by prazosin, is probably mediated by an alpha 1-adrenoceptor. An inhibitory action of serotonin was also apparent. The frequency and amplitude of spontaneous postsynaptic potentials and the response following dorsal root stimulation were markedly reduced. This action was mimicked by 5-carboxamidotryptamine and 8-hydroxy-2-(n-dipropylamino)tetralin, but was not antagonized by ketanserin (1 microM), ritanserin (1 microM), methiothepin (1 microM), metergoline (1 microM), spiperone (1-10 microM) or 21-009 (1-10 microM). It is proposed that the depolarization and increase in excitability of spinal motoneurons is mediated by a serotonin (5-HT2) receptor subtype. PMID- 1584409 TI - Serotonin1 and serotonin2 receptors hyperpolarize and depolarize separate populations of medial pontine reticular formation neurons in vitro. AB - The action of serotonin on medial pontine reticular formation neurons was examined using intracellular electrophysiological methods in rat brainstem slices in vitro. A hyperpolarization associated with a decrease in input resistance was elicited by serotonin in 34% of the neurons, and a depolarization associated with an increase in input resistance was produced in 56% of the neurons. Both responses persisted in the presence of tetrodotoxin. The hyperpolarization resulted from a steady-state increase in outward current which varied with the external potassium concentration in a manner consistent with a conductance increase primarily to this ion. This response was mimicked by the serotonin1 agonist, 5-carboxamidotryptamine, as well as by the serotonin1a agonist, 8 hydroxy-dipropyl aminotetralin hydrobromide, and was blocked by spiperone, an antagonist of serotonin1 sites. The depolarization resulted from a steady-state decrease in outward current which varied with external potassium. The depolarization was mimicked by the serotonin2 agonist, alpha-methyl-5 hydroxytryptamine, and was blocked by the serotonin2 antagonist, ketanserin. Neither of these agents had any effect upon serotonin-induced hyperpolarizations. In conclusion, the excitability of medial pontine reticular formation neurons is influenced by serotonin acting to increase or decrease potassium conductance(s). These opposing effects reflect actions on distinct serotonin receptor subtypes that are segregated to distinct populations of medial pontine reticular formation neurons. PMID- 1584411 TI - Omega-conotoxin differentially blocks acetylcholine and adenosine triphosphate releases from Torpedo synaptosomes. AB - We have examined the effect of several blockers of voltage-sensitive calcium channels on the release of acetylcholine and ATP from synaptosomes isolated from Torpedo marmorata electric organ. Depolarization of these nerve terminals with high K(+)-containing solutions resulted in a calcium-dependent release of both molecules. Cadmium ions (10(-6) to 10(-3) M) inhibited similarly both releases whereas nickel ions (10(-4) M) in the external medium did not affect either neurotransmitter or nucleotide release. Both releases were completely resistant to the effect of 1,4-dihydropyridines (antagonists nimodipine, nifedipine and agonist Bay K 8644) and of a related compound (diltiazem) at concentrations up to 10(-5) M. These drugs failed to cause any effect even when synaptosomes were submaximally depolarized during incubation. Omega-conotoxin (10(-8) to 5 x 10(-5) M) showed a differential effect on acetylcholine and ATP releases. Nucleotide release was inhibited 90% at the highest concentration tested (50 microns) while acetylcholine release was only moderately decreased (30%). EC50 values for acetylcholine and ATP were of 167 and 2 microM respectively. The results suggest the implication of different types of calcium channels in the release of these molecules. PMID- 1584410 TI - Electrophysiological, biochemical, and behavioral studies of acute haloperidol induced depolarization block of nigral dopamine neurons. AB - The electrophysiological, biochemical and behavioral responses produced by administration of haloperidol were studied in intact rats and in rats with 6 hydroxydopamine-induced partial lesions of the nigrostriatal dopamine pathway. In both control rats and rates tested four to 10 days postlesion, the electrophysiological response of nigral dopamine neurons to increasing doses of haloperidol consisted of either: (1) an increase in firing rate which reached a plateau at six to 10 spikes per second, or (2) no response (i.e., less than 20% change in firing rate). Administration of additional doses of haloperidol up to lethal levels did not elicit further changes in dopamine cell firing in these rats. In contrast, in 6-hydroxydopamine-treated rats tested four to six weeks postlesion, acute administration of haloperidol was not only more consistent in producing increases in dopamine cell firing rate, but also caused six out of seven dopamine neurons tested to cease firing upon entering a state of depolarization block. In all cases in which depolarization block was observed, dopamine cell firing was reinstated by either iontophoretic application of gamma aminobutyric acid or intravenous administration of apomorphine. In parallel studies, haloperidol caused an increase in the extracellular dopamine levels measured by microdialysis in the striatum of control rats, whereas administration of the same dose of haloperidol to 6-hydroxydopamine-treated rats four to six weeks postlesion did not elicit any change in extracellular dopamine levels. In addition, administration of haloperidol at a dose which was ineffective in control rats produced gross motor deficits in the 6-hydroxydopamine-treated rats when tested four to six weeks postlesion. These results show that 6 hydroxydopamine-induced dopamine depletions produce a time-dependent change in the responsivity of the nigrostriatal dopamine system to acute haloperidol administration. In this altered system, the induction of depolarization block of spike activity in nigral dopamine neurons by haloperidol was not associated with a corresponding decrease in extracellular dopamine levels measured in the striatum. However, it appeared that depolarization block did prevent haloperidol induced increases in extracellular dopamine levels. The occurrence of depolarization block in the dopamine-depleted animal may limit the capacity of this system to respond to additional compromise, in spite of the compensatory processes that contribute to maintaining motor function. PMID- 1584412 TI - Effects of lectins on quantal release at the frog neuromuscular junction. AB - This work was initiated because pretreatment with concanavalin A was reported to abolish the increase in spontaneous quantal release produced by hypertonic solutions [Gorio A. and Mauro A. (1979) J. gen. Physiol. 73, 245-263]. This suggested that lectins might be valuable tools for investigating the role of glycoproteins in the response to tonicity. We compared muscles soaked for 2 h in hypertonic solution containing concanavalin A with paired muscles soaked in hypertonic solution without lectin. The lectin treatment decreased miniature end plate potential frequencies in Ringer and in hypertonic solutions compared with the controls. Even after lectin treatment hypertonic solutions and elevated K+ solutions increased miniature end-plate potential frequencies, and the proportional increases were the same as in controls. The lectin treatment lowered baseline frequency, but the preparation still responded to hypertonic solutions. Concanavalin A effects appeared after treatment for more than 1 h and required concentrations of 10 micrograms/ml or higher. Higher concentrations did not produce more effect. Similar results were obtained with four other lectins with different sugar specificities. Treatment in hypertonic solution without lectin produces a similar, but smaller, decrease in baseline frequency. Concanavalin A pretreatment had no detectable effects on evoked release or facilitation. We conclude that the effects of lectins on quantal release are not mediated by binding to a single sugar group. The lectins do not produce a unique effect; they exaggerate the changes produced by hypertonic pretreatment. All of the effects could be accounted for by a reduction in baseline [Ca2+] in the nerve terminal. Such reductions are produced by lectins in many cell types. PMID- 1584413 TI - Synaptic activation of dorsal horn neurons by selective C-fibre excitation with capsaicin in the mouse spinal cord in vitro. AB - Low doses (0.2-0.8 microM) of capsaicin were used to achieve selective excitation of C-fibres and the consequent synaptic activation of dorsal horn neurons (laminae I-VI) in the spinal cord of the 12-20-day-old mouse, maintained in vitro. Most dorsal horn cells were activated by application of capsaicin to dorsal root ganglia. The response consisted of a long-lasting membrane depolarization with increased regenerative (synaptic) activity in 79% of the cells, and in a further 7% only an increased synaptic activity was evoked. These effects of capsaicin were completely blocked by removing extracellular calcium ions from the superfusate to the spinal cord, or by the addition of 1 microM tetrodotoxin, suggesting a presynaptic origin of the capsaicin action. Only 67% of cells excited by capsaicin were sensitive to exogenous substance P. The excitatory amino acid antagonists, kynurenic acid (50-100 microM) or (-)-2-amino 5-phosphonovaleric acid (10-20 microM) completely blocked the capsaicin-evoked response in deep dorsal horn cells, indicating the involvement of excitatory amino acid receptors in the synaptic pathway. However, in superficial dorsal horn neurons these antagonists attenuated, but never completely abolished, the capsaicin-evoked depolarization. The kynurenic acid-resistant component of the capsaicin-evoked excitation in superficial dorsal horn cells suggests the involvement of non-amino acid excitatory transmitters--possibly neuropeptides--in the synaptic transmission. Activation of primary afferents by high-intensity electrical stimulation of the dorsal roots induced a prolonged (0.5-3 s) postsynaptic excitation in the majority of deep dorsal horn cells. The duration of the synaptic response was significantly reduced by (-)-2-amino-5 phosphonovaleric acid. Following repeated application of capsaicin, desensitization of the capsaicin-evoked synaptic activation of dorsal horn cells occurred. This effect was paralleled with the loss of the prolonged (-)-2-amino-5 phosphonovaleric acid-sensitive phase of the excitatory postsynaptic potential evoked by the high-intensity electrical stimulation of dorsal roots. This observation suggested that activation of the N-methyl-D-aspartate receptors in the dorsal horn can be activated by small-calibre capsaicin-sensitive fibres. In summary, our data suggest that the selective activation of C-fibre afferents with capsaicin produces synaptic activity in the dorsal horn which has a strong excitatory amino acid component as well as a non-excitatory amino acid, possibly peptidergic, component. PMID- 1584414 TI - The relationship between unmyelinated afferent type and neurogenic plasma extravasation in normal and reinnervated rat skin. AB - Electrophysiological experiments have been carried out on rats to examine the relationship between plasma extravasation into skin and antidromic activation of individual unmyelinated afferent fibres supplying cutaneous receptors, particularly polymodal nociceptors. Normal animals and ones in which the skin had been reinnervated after peripheral nerve transection 26-52 weeks before were studied. In the normal animals 12 of 18 (66%) polymodal nociceptor afferents showed evidence of plasma extravasation after antidromic stimulation of the nerve filament from which they were initially recorded. Antidromic stimulation of other types of unmyelinated unit gave no detectable signs of plasma extravasation. The results from the animals with regenerated nerves were similar with 15 of 21 (71%) of the polymodal nociceptor afferents showing clear signs of plasma extravasation after antidromic activation and the other types of unit giving no signs of such a response. These results show that while antidromic stimulation of a cutaneous nerve after intravascular administration of Evans Blue dye can be used to get a general view of the extent of innervation by polymodal nociceptors, it does not necessarily show the entire distribution of these receptors. It is likely that the ability or lack of ability of a polymodal nociceptor afferent to enhance vascular permeability, and so bring about plasma extravasation, is related to its neuropeptide content, and thus it follows that this might be a useful criterion for separating this broad class of cutaneous receptor into sub-groups. PMID- 1584415 TI - Glial cells: possible determinants of neuronal uptake of tritiated proline. AB - When tritiated proline is injected into various sensory and integrative areas of the brain, it fails to be incorporated into the proteins of neuronal soma located within the injection site. In contrast, such incorporation does occur when [3H]proline is injected into dorsal root ganglia. The basis for this difference is unclear because brain and dorsal root ganglion tissue differ in configurational factors (e.g. synapses, dendrites) as well as in the embryological origin of their respective neuronal and non-neuronal cell populations. To determine if configurational factors might account for [3H]proline's incorporation into somal neuronal proteins in dorsal root ganglia, [3H]proline was injected into autonomic (pelvic and superior cervical) and sensory (dorsal root and nodose) ganglia in the rat. These ganglia differ in synaptic and cellular configurations, but have the same neural origin (neural crest). Virtually all neuronal soma were labeled in autoradiograms of all of these injection sites, suggesting that configurational factors do not account for the labeling of dorsal root ganglion neurons by [3H]proline. To address the issue of embryological origin, cellular labeling patterns after [3H]proline injection into the hypoglossal nucleus, dorsal motor nucleus of the vagus and the ventral horn of spinal cord were compared with those after [3H]proline injections into the adjacent solitary nucleus, gracile nucleus and central cervical nucleus of the spinal cord. The neurons in the former three nuclei (i.e. motoneurons) originate from the neural tube, but their axons are associated primarily with Schwann cells which originate from the neural crest. Although neurons in the latter three regions also originate from the neural tube, their axons are myelinated entirely by neural tube-derived glia (i.e. oligodendrocytes).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584416 TI - Distribution and ontogeny of parvalbumin immunoreactivity in the chicken retina. AB - The distribution of parvalbumin-like immunoreactivity was studied in the embryonic and postnatal chicken retina. In post-hatched chickens, parvalbumin like immunoreactivity was confined to amacrine cells. Three distinct subpopulations were identifiable based upon soma position and level of dendritic arborization in the inner plexiform layer. The primary dendrites from parvalbumin immunoreactive amacrine cells descended vertically into the inner plexiform layer and eventually branched to give rise to a laminarly arrayed plexus in sublamina I, sublamina V and, to a lesser extent, at the boundary between sublaminae III and IV. Parvalbumin-like immunoreactive amacrine cells projecting to sublamina I of the inner plexiform layer were consistently monostratified. Some, but not all, contributed thick fibers to sublamina I that could be followed for long distances across the retina and were generally not radially organized. The parvalbumin-like immunoreactive cells that projected to sublamina V gave rise to a primary dendrite from which three to five fibers branched radially. Collateral branches of these same primary dendrites gave rise to the parvalbumin-like immunoreactive plexus at the interface between sublaminae III and IV. In prenatal chickens, parvalbumin-like immunoreactivity was not detected until embryonic day 14. At this time it appeared as a faint band at the inner nuclear layer-inner plexiform layer boundary in the central retina. By embryonic day 18 the intensity of immunoreactivity and the complexity of the arborizations of the parvalbumin-like immunoreactive dendrites approached that seen in the post-hatched chicken. In the chicken retina, parvalbumin-like immunoreactivity was displayed by morphologically distinct subpopulations of amacrine cells suggesting that these amacrine cells may subserve diverse functions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584417 TI - Calretinin is present in non-pyramidal cells of the rat hippocampus--I. A new type of neuron specifically associated with the mossy fibre system. AB - Calretinin-containing cells were visualized with immunocytochemistry in the rat dorsal hippocampal formation. Calretinin immunoreactivity was present exclusively in non-pyramidal cells in all layers of the dentate gyrus and the CA1-3 areas. Calretinin-positive neurons and processes were most abundant in the hilus of the dentate gyrus and in the stratum lucidum of the CA3 region. Several calretinin immunoreactive cells were located within the hippocampal fissure. A distinct band of calretinin-immunoreactive fibres occupied the superficial part of the granule cell layer and the lowest part of the molecular layer. Closer examination of the calretinin-positive cells revealed that they formed two distinct cell groups. One group of cells, found exclusively in the stratum lucidum of the CA3 area and in the hilus of the dentate gyrus, was covered with numerous spines. Their somata and dendrites were restricted to stratum lucidum and to the hilus. Cells of the other group had smooth, often varicose, radially running dendrites, and were present in all areas and layers of the hippocampal formation. Two to three thick primary dendrites arose from the irregularly shaped cell body of spiny cells and emitted fine secondary branches only distally (70-100 microns) from the soma, where they formed a profuse network. The extensive dendritic tree of the cells spread horizontally within stratum lucidum and span a distance of 400-600 microns both in the septotemporal and in the transverse directions. The layer-specific location of these cells and their processes suggested that the majority of their input may derive from mossy fibres. This presumption has been confirmed by electron microscopic examination. A large number of asymmetrical synapses were found to cover the soma, the dendritic shafts and the spines (four to six synapses/spine) of the cells. A large proportion of the synapses were formed by boutons, which showed the distinctive features of mossy fibre terminals. Three to six primary dendrites arose from the multipolar, bipolar or pyramidal-shaped somata of spine-free cells, which were smaller than the somata of spiny cells. The smooth and frequently varicose dendrites branched proximally and ran primarily radially. Dendrites ascended or descended through several layers and received both asymmetrical and symmetrical synapses. In the CA1 subfield, the vertically running dendrites frequently contacted other calretinin-immunoreactive spine-free dendrites or cell bodies. Two or three calretinin-immunoreactive dendrites were often seen to be attached for over 100 or, occasionally, 200 microns and several puncta adherentia were observed between them using the electron microscope.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1584418 TI - Small cholinergic neurons within fields of cholinergic axons characterize olfactory-related regions of rat telencephalon. AB - Small immunoreactive cholinergic neurons were detected in the main and accessory olfactory bulbs of the rat with choline acetyltransferase immunocytochemistry. Such cells were also found in additional forebrain regions that received direct efferent innervation from the main olfactory bulb, such as the anterior olfactory nucleus, two subdivisions of the olfactory amygdala (nucleus of the lateral olfactory tract and anterior cortical nucleus), and the cortical-amygdaloid transition zone. Cholinergic neurons located in these olfactory-related regions were similar to each other morphologically and to those previously described by other investigators in the cerebral cortex, the hippocampus, and the basolateral amygdala. Somal measurements indicated that choline acetyltransferase-positive cells in olfactory-related regions were all essentially the same size, measuring 13-14 by 8-9 microns in major and minor diameters, respectively. In addition, these small cells were commonly bipolar in form with thin, smooth dendrites, and such characteristics have generally been associated with intrinsic, local circuit neurons in the forebrain. Depending on their location, however, these small cholinergic neurons differed from each other with regard to their frequency and dendritic orientation within planar sections. Choline acetyltransferase immunoreactive cells in most cortical regions were relatively numerous and usually exhibited long, planar dendrites oriented perpendicularly to the pial surface. In contrast, dendrites of cholinergic neurons found in "cortical-like" regions (e.g. olfactory bulbs or nucleus of the lateral olfactory tract) were relatively sparse in number and appeared to be distinctly non-planar and randomly oriented. Despite these differences, the small choline acetyltransferase-positive cells had many features in common, including their distribution within forebrain regions that contained substantial terminal networks of choline acetyltransferase positive axons thought to be derived primarily from the basal forebrain complex. In the rat, at least, the presence of small cholinergic interneurons within forebrain regions innervated by the large cholinergic projection neurons of the basal forebrain seems to be developing as a general principle of telencephalic organization. However, differences in both the size and the distribution of the terminal fields derived from each source imply a functional diversity between the intrinsic and extrinsic cholinergic systems of the forebrain. PMID- 1584419 TI - Characteristics of putrescine uptake and subsequent GABA formation in primary cultured astrocytes from normal C57BL/6J and epileptic DBA/2J mouse brain cortices. AB - Brain maturation and GABA metabolism are known to play a key role in epileptogenesis. The metabolism of the polyamines (putrescine, spermidine and spermine) is closely linked to the process of brain maturation. Putrescine has been shown to be catabolized to GABA in brain tissue and astrocytes. In order to better understand the importance of glial putrescine transport and metabolism, a model of age-dependent epilepsy was used to study the kinetic properties of [14C]putrescine uptake into cultured astrocytes from normal C57/BL and audiogenic DBA/2 newborn mice, and the subsequent GABA formation. (1) Putrescine uptake exhibited non-Michaelian allosteric kinetics with positive co-operativity (Hill factor = 2), suggesting a physiological importance of putrescine uptake by astrocytes. (2) The Vmax of putrescine uptake was significantly higher in C57/BL astrocytes than in DBA/2J, but the uptake affinity for putrescine was higher in DBA/2J than in C57/BL. (3) Higher K+ concentrations (18 mM) had little effect on putrescine uptake in either strain. (4) Ten-micromolar N-acetylputrescine, the first putrescine metabolite, stimulated putrescine uptake into astrocytes of both strains, but to a different degree: +46% in C57/BL and + 102% in DBA/2J. (5) The specific radioactivity of the GABA formed from labelled putrescine was four times higher in astrocytes from DBA/2J than from C57/BL mice. (6) The molar ratio of glutamate/GABA in the cerebral cortex of the DBA/2J mice was significantly higher during the period of audiogenic seizure susceptibility than in age-matched C57/BL mice. Our results show characteristics of putrescine uptake into astrocytes; we demonstrated distinct kinetic properties between normal and epileptic strains of mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584420 TI - Properties of postganglionic sympathetic neurons with axons in the right thoracic vagus. AB - The resting and reflex-evoked activities of single postganglionic sympathetic neurons with axons in the right thoracic vagus were tested in chloralose anaesthetized cats. The properties of a majority of neurons were found to be similar. Cardiac- and inspiration-related rhythmicities were present in the resting activity of sympathetic neurons. Their resting activity was not affected by hyperventilation which abolished phrenic nerve discharges. Systemic hypoxia (2 min; 8% O2 in N2) increased the activity of the neurons more effectively in the deafferented state than when both sinus nerves remained intact. Injection of 0.1 ml 1 M sodium bicarbonate saturated with CO2, which activates peripheral chemoreceptors in the right or left carotid sinus, usually evoked a decrease in sympathetic activity in animals with both sinus nerves intact. We concluded that activation of peripheral chemoreceptors may inhibit the activity of the sympathetic neurons with axons in the right thoracic vagus. We suggest that the described sympathetic neurons may be a functionally homogeneous population which may innervate the conducting system of the heart. The close localization of sympathetic and parasympathetic axons in the vagus nerve may facilitate sympathetic-parasympathetic interaction at the level of their endings in the heart. PMID- 1584421 TI - The acute inflammatory response to lipopolysaccharide in CNS parenchyma differs from that in other body tissues. AB - Acute inflammation is important for defence against infection, wound repair and the mediation of auto-immune tissue destruction. Myelomonocytic recruitment in acute inflammation is a stereotyped and non-specific response to tissue insult which begins within 2 h. In this study, lipopolysaccharide was injected into the murine CNS and other body sites of mice to compare the inflammatory responses. Doses of lipopolysaccharide which induced typical myelomonocytic recruitment in skin and the choroid plexus had no effect in CNS parenchyma, apart from the morphological activation of local resident microglia. The CNS parenchymal response proceeded independently of that in the choroid plexus-cerebral ventricles and had three distinct and unique phases. Initially there was minimal neutrophil exudation and a two-day delay before any increase in macrophage microglial cell number. Next, there was a rapid increase in macrophage-microglial cell numbers during the third day, mainly due to recruitment of blood monocytes. During this phase, leukocyte recruitment was restricted to monocytes which rapidly adopted the arborized microglial phenotype. Monocytes migrated through an intact blood-brain barrier independent of changes in solute permeability. Finally, there was a florid myelomonocytic reaction predominantly in the white matter, one week after intracerebral injection of 2 micrograms lipopolysaccharide. At this time, the leukocyte reaction disrupted the blood brain barrier, mononuclear phagocytes expressed macrophage morphology and abundant major histocompatibility complex Class II antigen, and T lymphocytes were present. Myelomonocytic entry into the CNS was partially inhibited by prior blockade of the type 3 complement receptor, known to mediate leukocyte adhesion to endothelium elsewhere. The processes which lead to rapid myelomonocytic recruitment in other tissues are absent in CNS parenchyma. Understanding the molecular mechanisms responsible could have considerable significance both for CNS pathophysiology as well as possible anti-inflammatory therapeutic application elsewhere in the body. PMID- 1584422 TI - Neural cell adhesion molecule in aged mouse muscle. AB - Expression of the neural cell adhesion molecule was compared in endplate and non endplate regions of skeletal muscles of mature and old CBF-1 mice, in order to determine whether age-related changes in neuromuscular morphology were correlated with age changes in neural cell adhesion molecule expression. Three muscles were examined: two (soleus and sternomastoid) showed age-related regionalization of nerve terminals as one manifestation of increased synaptic remodelling while the third (diaphragm) did not. Relative neural cell adhesion molecule content in these muscles was measured by densitometry of immunoblots after concentration by affinity chromatography. Expression of the major 140,000 mol. wt form of neural cell adhesion molecule, which was most abundant in the endplate region, was increased in sternomastoid and soleus of old compared to adult mouse, but was unchanged with age in diaphragm. A 70,000-80,000 mol. wt presumably proteolytic polypeptide fragment of neural cell adhesion molecule was increased in immunoblots of all old muscles. Immunocytochemical studies of skeletal muscles showed no difference in neural cell adhesion molecule cellular distribution in mature vs old mice, but in motor nerve of sternomastoid, the number of neural cell adhesion molecule-positive nerve fibers was increased in old mice. Several lines of evidence indicated that partial denervation was rare in old CBF-1 mice, and therefore could not account for the findings above. Selective increase of 140,000 mol. wt neural cell adhesion molecule expression in the junctional regions of those muscles of old mice which show neuromuscular remodelling indicates that this adhesion molecule may play a role in the age-related instability of motor nerve terminals. PMID- 1584424 TI - Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation. AB - Quantitative Golgi study of hippocampal pyramidal neurons of ground squirrels showed rapid and profound transformation of their apical dendrites in the course of hibernation. The dendrites were significantly shorter, less branched and had fewer dendritic spines in the middle of hibernation bout than in the active euthermic ground squirrels between bouts. After arousal from torpor, within 2 h dendrites completely restored their structure. During hibernation, season remodelling of the hippocampal dendrites occurs repeatedly during each torpor activity cycle. PMID- 1584423 TI - Calretinin is present in non-pyramidal cells of the rat hippocampus--II. Co existence with other calcium binding proteins and GABA. AB - The possible co-existence of calretinin with other calcium binding proteins, parvalbumin and calbindin D28k, and with GABA, was studied in non-pyramidal cells of the rat dorsal hippocampal formation, using the mirror technique. The majority of the calretinin-containing neurons (83%) were found to be immunoreactive for GABA (79% in the dentate gyrus, 84% in the CA2-3, and 88% in the CA1 subfield). Most of the GABA-negative calretinin-immunoreactive neurons were located in the hilus of the dentate gyrus and in stratum lucidum of the CA3 subfield. Detailed analysis of the calretinin-immunoreactive cells of these subfields revealed that the two morphologically distinct types of calretinin neurons, i.e. the spiny and the spine-free cells, differ in their immunoreactivity for GABA. The overwhelming majority (92%) of the spine-free neurons were GABA-positive, whereas the immunoreactivity of spiny cells was ambiguous. At the sensitivity threshold of the immunocytochemical techniques used in the present study, most of the spiny cells (89%) had to be considered as GABA-negative, although the staining intensity in their cell bodies was somewhat above background level. Colchicine treatment resulted in a degeneration of calretinin-immunoreactive neurons; therefore, its effect on the GABA content of spiny neurons could not be evaluated. Nevertheless, the observations suggest that calretinin-containing neurons are heterogeneous both morphologically and neurochemically. Examination of the co-existence of calcium binding proteins revealed that none of the hippocampal cells contained both calretinin and parvalbumin in any regions of the hippocampal formation. Some overlap was detected between the calretinin- and the calbindin D28k-containing cell populations, 5.1% of the former and 6.2% of the latter were immunoreactive for both calcium binding proteins. This may be due to a small degree of cross-reactivity of the calbindin D28k antiserum with calretinin. Thus, our results demonstrate that the majority of calretinin immunoreactive neurons are GABAergic and represent a subpopulation of non pyramidal cells with no or only a negligible overlap with the subpopulations containing the other calcium binding proteins, parvalbumin and calbindin. PMID- 1584425 TI - Hibernation-induced structural changes in synaptic contacts between mossy fibres and hippocampal pyramidal neurons. AB - Mossy fibre synapses on the CA3 hippocampal neurons in the brain of ground squirrels repeatedly undergo a striking structural transformation during hibernation. In the middle of hibernation bout the giant complex mossy fibre synapses have a reduced number of dendritic spine infoldings that are smaller and have a decreased number of postsynaptic densities in comparison with mossy fibre synapses of active animals. Two hours after arousal all these parameters of mossy fibre synapses increase and significantly exceed their levels not only in torpid but in active euthermic animals between bouts of torpor. The longer postsynaptic densities and the greater proportion of perforated postsynaptic densities were found soon after arousal. These rapid, reversible and repeated changes indicate a cyclic process of partial denervation/reinnervation of hippocampal neurons by mossy fibres in the course of the innate, stereotyped behaviour. PMID- 1584426 TI - Long-term potentiation induced by patterned stimulation of the commissural pathway to hippocampal CA1 region in freely moving rats. AB - In urethane-anesthetized rats, stimulation of the contralateral hippocampal CA1 region resulted in activation of the homotopic CA1 region. Current-source-density analysis revealed that both basal and apical dendrites were activated. However, alveolar and stratum oriens stimulation in CA1 gave about equal peak excitation of the basal and apical dendrites while CA1 stratum radiatum/moleculare and CA3c stimulation gave stronger apical than basal dendritic excitation. In chronically implanted and freely moving rats, tetanic patterned stimulation of the contralateral CA1, irrespective of depth, resulted in a robust long-term potentiation of the ipsilateral CA1 basal dendritic synapse. The population basal dendritic excitatory postsynaptic potential was initially potentiated to greater than 200% of the baseline and decayed with a 3 h time constant; it lasted at least two days. Patterned stimulation of the commissural inputs at 2 x threshold stimulus intensity seldom potentiated the apical dendritic synapse in CA1; rather, long-term depression was sometimes observed. After tetanic stimulations at 3 x threshold, a small potentiation of the apical dendritic excitation was seen in about half of the experiments. The average apical dendritic potentiation peaked at about 25% and persisted to at least one day. This study provides original evidence that the properties of long-term potentiation are different at the commissural basal dendritic and apical dendritic synapses in CA1 of the behaving rat. Basal dendritic potentiation is low-threshold, high-amplitude and decayed rapidly in the first 3 h. Apical dendritic potentiation is high threshold, low-amplitude and not rapidly decaying. A long-lasting enhancement of synaptic transmission has been postulated as a physiological correlate of memory. This paper reports properties of this synaptic enhancement for two different types of synapses on the same cells in the behaving animal. The basal dendritic synapse on hippocampal pyramidal cells readily increased their efficacy, up to at least two days, after a brief, patterned stimulation. In the same preparation, it was difficult to obtain a long-lasting increase in the apical dendritic excitation, in contrast to studies on isolated hippocampal slices in vitro. PMID- 1584427 TI - Intracellular evidence for incompatibility between spindle and delta oscillations in thalamocortical neurons of cat. AB - Recent studies have revealed that the thalamus does not only generate spindle oscillations (7-14 Hz), but that it also participates in the genesis of a slower (less than 4 Hz) rhythm within the frequency range of delta waves on the electroencephalogram. In thalamic cells, delta is an intrinsic oscillation consisting of low-threshold spikes alternating with afterhyperpolarizing potentials. It is known from electroencephalographic recordings in humans and animals that slow or delta waves prevail during late sleep stages, whereas spindle oscillations are characteristic for the early stages of sleep. We studied the dependence of spindles and delta oscillations on membrane potential, as well as the effects of spindles on delta oscillations, in thalamocortical neurons of cats under urethane anesthesia and in cerveau isole preparations (low collicular transections). Spindles appeared at membrane potentials between -55 and -65 mV, whereas delta oscillations occurred by bringing the membrane potential between 68 and -90 mV. Spindles either evoked by cortical stimulation or occurring spontaneously in cerveau isole preparations prevented delta oscillations. This effect was probably due to the increase in membrane conductance associated with spindles. Barbiturates also blocked delta activity in thalamocortical neurons, probably through the same mechanism. A certain degree of incompatibility between spindles and delta rhythms in thalamocortical cells may explain the prevalence of these two types of oscillations during different stages of sleep with synchronization of the electroencephalogram. PMID- 1584428 TI - Morphology of intracellularly stained spiny neurons in rat striatal grafts. AB - Two to six months after implantation of fetal striatal primordia into the kainic acid-lesioned neostriatum of adult rats, spiny neurons in the grafts were stained intracellularly with biocytin. To determine whether the spiny neurons in the grafts differentiate morphologically as in the host neostriatum, the intracellularly stained spiny neurons in the grafts were studied with light and electron microscopy and compared with that of spiny neurons in the host neostriatum. The spiny neurons in the grafts had ovoid or polygonal cell bodies with dendrites radiating in all directions. The somata were smooth and the dendrites, except for their most proximal portions, were rich in spines. All these features resembled the appearance of spiny neurons in the intact neostriatum. However, quantitative studies showed that the somata of spiny neurons in the grafts were larger than those in the host neostriatum (projected cross-sectional areas of 230 +/- 64.6 microns 2 in the grafts and 158 +/- 28.9 microns 2 in the host) and the spine density of graft neurons was lower than that of host neurons. Cells near the border of the grafts had dendrites extending both into the graft and into the host neostriatum. In these cells, the dendrites in the grafts had fewer spines than the dendrites in the host tissue. The axons of spiny neurons in the grafts had very large and dense intrastriatal collateral arborizations, which occupied a much larger volume than that of the dendritic domain of the parent cells. The local axonal arborizations of each of these cells filled almost the entire graft. In some cells, axonal branches were traced outside the grafts and were seen to enter the internal capsule fascicles. Unlike spiny neurons in the normal adult neostriatum, the spiny cells of the graft could have nuclear indentations. With this exception, the ultrastructural features of spiny neurons in the grafts were very similar to those in the hosts. Many unlabeled boutons made synapses on identified spiny neurons in the grafts. Terminals with small round vesicles made synaptic contacts on dendritic shafts and dendritic spines, while terminals with flattened or pleomorphic vesicles contacted somata, dendrites, and dendritic spines. Labeled axon collaterals of graft neurons made symmetrical synapses on somata, dendrites and spines in the grafts and in the host neostriatum. In the grafts, more than 60% of the axon terminals contacted dendritic shafts. The proportion of axosomatic and axospinous synapses varied substantially from cell to cell.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584429 TI - Does selegiline monotherapy in Parkinson's disease act by symptomatic or protective mechanisms? AB - Selegiline monotherapy has been clearly demonstrated to delay the development of disability in early, otherwise untreated Parkinson's disease patients. It remains uncertain, however, whether this benefit is due to protective effects on residual neurons or to symptomatic effects that mask the detection of underlying disability. This paper examines the evidence and theory supporting the hypotheses that selegiline acts by protective or symptomatic mechanisms and considers what future studies might help clarify these issues. PMID- 1584430 TI - Long-term experience with selegiline and levodopa in Parkinson's disease. AB - Between 1982 and 1989, 197 patients with Parkinson's disease were treated with selegiline and levodopa for at least 0.3 years. Two groups of patients were included: a group of 65 patients (stage 2 or 3 on the Hoehn and Yahr Scale) who recently had been started on levodopa and were not experiencing response fluctuations, and a group of 132 patients on levodopa who were experiencing fluctuations. More nonfluctuating than fluctuating patients improved, although the differences were not significant; a higher percentage of fluctuating patients worsened, compared with nonfluctuating patients, and these differences were significant. The percentage of patients who were stable was similar between the two groups, and adverse effects were minor and reversible. Our study suggests that among patients on levodopa, fewer patients worsen when selegiline is added earlier than when it is added later. PMID- 1584431 TI - Emerging perspectives in Parkinson's disease. PMID- 1584432 TI - Natural history and choice of treatment in forty patients with medullary venous malformation (MVM). AB - Follow-up studies of forty patients with forty-one medullary venous malformations (MVM's) are described. The patients included nineteen males and twenty-one females in an age range from eight to seventy-two years (mean 43.4 years). All cases were diagnosed angiographically. Of the forty-one lesions, twenty-five were located in supratentorial and sixteen in infratentorial regions. In twenty-five supratentorial MVM's, thirteen had superficial drainage, eight deep drainage and three both superficial and deep drainage. Fifteen patients presented with intracranial hemorrhage and eleven patients with complaints or symptoms not related to hemorrhage. Fourteen hemorrhages were found incidentally. The mean follow-up period was three years and eleven months and the longest was sixteen years. No patient died of recurrent hemorrhage and only two had recurrent hemorrhage after a short interval. One patient died of malignant glioma. Thirty seven out of thirty-nine patients (95%) were in an excellent or good clinical condition with a score above 80% on the Karnofsky Performance Test. This study indicates the low incidence of rebleeding in ruptured MVM's (2/15, 13.3%) and of bleeding in incidentally found unruptured MVM's (0/25, 0%). However, this evidence may be sufficient to support aggressive radical surgery for MVM's. PMID- 1584433 TI - Aspirin as a risk factor for hemorrhage in patients with head injuries. AB - The role of aspirin as a risk factor in the occurrence of intracranial bleeding following head injury was investigated. Chronic subdural hematoma appears to be a suitable model for the evaluation of risk factors in the development of hemorrhage. The most common risk factors found in our study were, apart from age, chronic alcohol abuse (28%), consumption of cumarin-derivates (21%), aspirin (13%), and heparin (5%). A patient undergoing aspirin treatment must be considered at risk of development of chronic subdural hematoma. Aspirin should not be prescribed to patients with post-traumatic headaches. PMID- 1584434 TI - Subarachnoid hemorrhage of unknown origin. Longterm prognosis. AB - Patients suffering subarachnoid hemorrhage in whom angiography does not initially show vascular malformation and CT scan rules out an intracranial tumor, have, reportedly, a good prognosis with a rate of recurrent hemorrhage of about 2-10% within a follow-up time of up to 15 years. Most authors denied indication for control angiography. In order to study the benefit of control angiography performed after 4-6 weeks, four-hundred eighty-three patients with SAH but without ICH were reveiwed, and the longterm clinical course of 98 patients with SAH of unknown origin treated in our department between 1976 and 1988 was investigated. Among 183 patients who underwent control angiography, a second angiography showed an aneurysm in 143. The third angiography was positive in a further 18 patients. Recurrent SAH occurred early only in patients who had undergone only one angiography. One patient died from intracerebral hemorrhage of unknown origin two years following SAH. These data support the need for control angiography in cases of SAH. PMID- 1584435 TI - The results of surgery for intracerebral hematomas. AB - Our retrospective study included 104 patients (28 female and 76 male) with intracerebral bleeding, treated between 1978 and 1988 in the Neurosurgical Clinic of the Medical University in Hannover. The average age was 43 years. 53 patients presented with traumatic intracerebral bleedings, and 51 with spontaneous hematomas. 31 patients with spontaneous hematomas were operated: among these a good or satisfactory result was obtained in 19 patients, and 12 died. Of the 20 non-operated patients, a good or satisfactory result was achieved in 10. 31 patients were operated in the group with traumatic hematoma, of these 22 had a good or satisfactory outcome and 9 patients died or had an unsatisfactory result. Of the 22 non-operated patients, 13 died and 9 achieved a good or satisfactory result. In the stratified Chi2-Test the effects of the operation were not found to be significant, with 0.1 less than p less than 0.25 for spontaneous, and 0.25 less than p less than 0.05 for the traumatic hematomas. There is a trend in favor of the operation in certain cases. PMID- 1584436 TI - Transcranial Doppler ultrasound in internal carotid artery and middle cerebral artery disease. AB - Using noninvasive transcranial Doppler sonography, we studied cerebral collateral patterns in 30 patients with stenosis and/or occlusion of the extracranial internal carotid artery (ICA). All patients with unilateral ICA stenosis less than or equal to 80% had normal transcranial Doppler findings. 80% of patients with unilateral and 50% of patients with bilateral ICA stenosis of more than 80% including those with occlusion showed a collateralization via the ipsilateral anterior and/or posterior cerebral artery. 20% of patients with unilateral and 50% of patients with bilateral ICA stenoses of more than 80% (including occlusion) had two or three collateral pathways, including the ophthalmic artery. Another ten patients with stenosis or spasm of the middle cerebral artery (MCA) showed increased flow velocities with turbulence in the narrow segment. In four patients with severe MCA disease with a systolic peak velocity of more than 200 cm/s, the Doppler waveform distal to the lesion was damped. Decreased regional cerebral blood flow (rCBF) measured by 99mTc-HMPAO-SPECT was found in two patients with severe MCA stenosis. Another patient with moderate MCA stenosis with a systolic peak velocity of 140 cm/s showed a normal cerebral perfusion pattern. PMID- 1584437 TI - Surgical management of craniocerebral gunshot wounds. AB - Thirty-nine cases operated on because of gunshot wounds in our clinics the years 1976-1986 have been investigated. Factors contributing to mortality and outcome were evaluated. All the principles of emergency medical care and of surgical treatment of penetrating wounds should be applied to those patients with craniocerebral gunshot wounds in whom surgery is indicated. PMID- 1584438 TI - CBF studies with Xenon-133 in arteriovenous malformations: a methodological study. AB - A new model for the two dimensional rCBF technique using the inhalation of Xenon 133 was tested in patients with arteriovenous malformations. It was hypothetized that, in contrast to the conventional CBF model, it corrects for the artifactual shunt flow through the AVM and thus yields physiological CBF data. Four regions of interest (AVM, contralateral to AVM, ipsilateral hemisphere, contralateral hemisphere) were defined in 17 patients with AVMs and analyzed for differences in grey matter flow (F1). In contrast to the conventional CBF model, the new model shows a decreased flow over the AVM area, corresponding to the results of Xenon CT and SPECT. Furthermore, the blood pool parameter P4 is very sensitive to the location of the AVM. Thus further investigations of the hemodynamics of AVMs with this model are encouraged. PMID- 1584439 TI - Characteristic EEG findings in childhood moyamoya syndrome. AB - Moyamoya syndrome-specific alterations of EEG recordings are only observed in children. These consist of a gradual frequency decrease and amplitude activation after hyperventilation. This is referred to as re-build-up phenomenon. Thus, a tentative diagnosis of Moyamoya syndrome in children can be based on the EEG finding. This should be radiologically confirmed by angiography. PMID- 1584440 TI - Report of dissection of the internal carotid artery in three cases. AB - Whereas previously the dissection of arteries leading to the brain was thought to be a rare occurrence, this diagnosis has been found more frequently in the last years as a result of newer imaging methods. Furthermore, in contrast to earlier opinions, there is a rather good prognosis for the recanalisation of the vessels and the restoration of the patient's health. In this paper, three cases with nearly typical constellation of symptoms and beneficial outcome are demonstrated. The related Doppler sonographical findings including duplex scan as well as the angiographical, computer tomographical and magnetic resonance tomography results are reported. It is to be noted that none of the three patients had a severe trauma or belonged to typical risk groups for a spontaneous dissection (Marfan's Syndrome, fibromuscular dysplasia. PMID- 1584441 TI - Subependymoma of the spinal cord. Case report and review of the literature. AB - Subependymoma is an uncommon, benign and, as a rule, asymptomatic lesion of the central nervous system, only rarely recorded at spinal level. The case reported here brings the total number of spinal subependymomas so far described to 16. The relevant literature is reviewed and the salient features of these tumors are discussed. PMID- 1584443 TI - [Mechanical resistance of intrauterine devices. Experimental evaluation]. AB - In view of the possible intracavitary breakage of an IUD, an experimental model was created to evaluate resistance to mechanical stress in new IUDs and IUDs which had been used for varying periods (6-12-24 months). The results of the study showed that, in addition to a slight inhomogeneity of the product which is probably due to incorrect industrial manufacturing procedures, there is also a correlation between the risk of breakage and intrauterine ageing which is particularly evident in some IUDS. PMID- 1584442 TI - Tuberculoma of pineal area. Case report. AB - A case of pineal area tuberculoma revealed by grand mal seizures and deterioration of vision is presented. A surgical biopsy and chemotherapy produced good results. This unusual site of tuberculoma demonstrates the usefulness of a direct approach to pineal area masses. It also confirms the effectivity of chemotherapy for tuberculoma. PMID- 1584444 TI - [Massive subchorionic fibrin deposit: echographic diagnosis]. AB - Intra-placental sub-chorionic fibrin deposition is a frequent finding but generally does not involve alterations of hemodynamics or the organ's gaseous metabolism. If the deposition is massive, as in the two cases reported here, delayed fetal growth may occur due to altered placental function. Diagnosis using ultrasound is useful both to identify fibrin plaques and to identify possible fetal hypo-development. PMID- 1584446 TI - [Value of the Pap-test in the cervical cytological screening]. AB - Fourteen thousand three hundred fifty six cervical smears were performed in the Obstetric and gynaecologic Department of Casorate Primo Hospital (USSL no. 77) and Oncologic Center of Milan (USSL no. 75/II) between 1-1-1987 and 30-6-1991. The incidence and mortality of uterine cervix neoplasm are discussed and the uterine cervix neoplasm are discussed and the analysis of data shows a reduction of this cancer in all countries. In italy it is estimated that the incidence is of 20.88 per 1000,000 women of all ages. PMID- 1584445 TI - [A new rapid method for the diagnosis of Chlamydia trachomatis in the obstetric gynecologic field]. AB - Kodak Surecell Kit, a new immunoenzymatic test for Chlamydia detection, was evaluated. The Authors compared the sensitivity, specificity and cost between the tissue culture and the immunoenzymatic test. They conclude that the immunoenzymatic test, Kodak Surecell, is sufficiently faithful. It is a rapid and cheap method. PMID- 1584447 TI - [Obstetric and perinatal morbidity and mortality in gestational hypertension]. PMID- 1584448 TI - [Changes in sexual behavior of women receiving substitution therapy after surgical menopause and women in physiological menopause]. AB - We have made this study with the aim of comparing changes in sexuality between women who are in surgical menopause taking a substitutive therapy and those who are in physiological menopause. We have used a questionnaire instrument. It has been filled in by a physician during an individual conversation with the women. The results showed that sexuality valued through the parameters of satisfaction, coital frequency and desire, has been have penalized in the first group than in the second. It can be said that the trauma linked to hysterosalpingo-oophorectomy provokes alterations in sexuality which are not sufficiently counterbalanced by substitutive estrogenic therapy. PMID- 1584449 TI - [Vertical transmission of hepatitis B and its prevention]. PMID- 1584450 TI - [Therapeutic plans for the treatment of HPV infections by systemic administration of interferon-alpha. Experience with preneoplastic pathology of the uterine cervix associated with viral cytopathic effects]. AB - The principal action of IFN is anti-viral, rather than antiproliferative and immunomodulatory. All three actions are required to resolve pre-neoplastic uterine cervix pathologies, above all if they are at an early stage or associated with viral cytopathic effects. PMID- 1584451 TI - [Association between inguinal endometriosis and polycystic ovary]. AB - A case of inguinal endometriosis is described in a patient affected by PCOD. To the best of our knowledge, this is the first case of this type of association reported in the literature although cases in which endometriosis was related to high estrogen levels are well documented. We suggest that in the presence of high estrogen levels (absolute or relative hyperestrinism), the foci of endometriosis might not prove a rare condition if clinicians and pathologists lashed for it carefully. PMID- 1584452 TI - [Large size solitary luteinizing follicular cysts in puerperium]. AB - One case of large solitary luteinized follicle cyst of puerperium is reported. The patient presented with a palpable adnexal mass at four weeks post-partum. The ovarian cyst was solitary and unilocular and had a diameter of 14 cm. On microscopical examination the lining of the cyst consisted of luteinized cells that exhibited focal nuclear atypicality. PMID- 1584453 TI - [Obstetric complications associated with DIC. Importance of D-dimer in the diagnosis and treatment. A clinical case]. AB - The case of a 32-year old woman with 36-week pregnancy presented at hospital because of spontaneous vaginal bleeding, anemia and mild hypotension is reported. Fetal mors in utero, abruptio placentae and diffuse intravascular coagulation were diagnosed. The patient subsequently underwent cesarean section and large retroplacental hematoma was removed and obviously fetum. The DIC was easily controlled by means of recently introduced method of determination of fibrin D dimer. PMID- 1584455 TI - Odor-induced fos-like immunoreactivity in the rat olfactory bulb. AB - We here report odor-induced mapping patterns of c-fos-like protein (Fos) immunoreactivity in the rat olfactory bulb under urethane anesthesia. Regional patterns of cells with nuclei expressing Fos, plotted on a spread-out reconstruction of the mitral cell layer, were strikingly comparable to data from the 2-deoxyglucose method, by which different foci of the most-labelled glomeruli of metabolic activity were demonstrated using different odors. Cells in the glomerular, external plexiform, and granule cell layers were also labelled. PMID- 1584454 TI - Histamine H1 receptors in human brain visualized in vivo by [11C]doxepin and positron emission tomography. AB - Histamine H1 receptors in the living human brain were visualized by positron emission tomography (PET) using [N-11C-methyl]-(E)-doxepin ([11C]doxepin). The regional distribution of the carbon-11-labeled compound in the brain corresponded well with that of the histamine H1 receptors measured in vitro using [3H]pyrilamine. The radioactivity in the brain was significantly reduced by intravenous pretreatment with d-chlorpheniramine (5 mg), a histamine H1 antagonist. The regional distribution of [11C]doxepin in the brain 45-90 min after its injection was almost the same as that of [11C]pyrilamine in the brain. These results indicate that [11C]doxepin is useful for measuring histamine H1 receptors in human brain by PET. PMID- 1584456 TI - Effects of an eight-hour advance of the light-dark cycle on sleep-wake rhythm in the rat. AB - We observed effects of an 8-h advance of the light-dark (LD) cycle on the sleep wake rhythm in the rat. On the day phase-advanced, rapid eye movement (REM) sleep increased with its enhanced diurnal amplitude. Non-REM (NREM) sleep gradually increased in parallel with the decrease of its diurnal amplitude. Although the acrophase of NREM sleep gradually advanced after the phase advance, that of REM sleep did not significantly change. We confirmed that diurnal rhythm of REM sleep was hardly shifted and dissociated from the rhythm of NREM sleep under the eight hour advance of the LD cycle in the rat. PMID- 1584457 TI - Changes in cerebral energy metabolism and calcium levels in relation to delayed neuronal death after ischemia. AB - Using a brief transient ischemic model, we examined changes in regional tissue calcium content and energy metabolism in the hippocampus. In the CA1 region, tissue calcium ions began to increase 24 h after reperfusion, accompanied by changes in tissue pH and ATP. In the CA3 region, energy metabolism remained unchanged for 72 h after reperfusion, and the calcium pool was first noted 24 h after reperfusion, while tissue calcium ions began to increase 48 h after reperfusion. These results suggest that the neurons in the CA3 region seem to survive because of the well-preserved metabolic function to cope with excessive calcium ions. PMID- 1584458 TI - Melatonin suppression in human subjects by bright and dim light in antarctica: time and season-dependent effects. AB - Full-spectrum light, of sufficiently high intensity, will suppress the secretion of melatonin at night in humans. Individual sensitivity to such suppression is variable, and the factors determining such sensitivity are largely unknown. By analogy with animal work previous short or long-term exposure to different light intensities may be an important determinant. We exploited the Antarctic environment to investigate these possibilities. Groups of healthy men, living on the British Antarctic Survey Base at Halley (75 degrees South) were exposed to dim (range 290-310 lux) and bright (range 2100-2300 lux) light either from 01.00 02.00 h or 05.00-0.600 h, both in winter and in summer. Plasma melatonin concentrations were determined by radioimmunoassay in serial blood samples taken before, during and after light treatment, and in control (darkness) conditions. Light suppression of melatonin was more effective in the latter part of the night in winter and this was particularly well-differentiated for dim light. PMID- 1584459 TI - Early stimulation effects on novelty-induced behavior in two psychogenetically selected rat lines with divergent emotionality profiles. AB - The present study shows that postnatal handling (H: consisting of removing the pups from the nest twice daily and placing them individually in plastic cages lined with paper towel for a period of 10 min, between postnatal days 1 and 21) and/or environmental enrichment (E: for a period of 6 months) of Roman high- and low-avoidance (RHA/Verh and RLA/Verh) rats induced long-lasting decreases in emotional reactivity (i.e. reduced defecations in the open field, OF, and hole board, HB, tests) as well as increases in exploratory behavior (i.e. head dipping) in a manner dependent upon the rat line (there were 'line x H' and 'line x E' interactions). It is reported for the first time that RHA/Verh rats show more head-dipping behavior than RLA/Verh rats, and that the environmental treatments can increase head-dipping of RLA/Verh animals to the level shown by RHA/Verh rats. PMID- 1584460 TI - Plasticity of the frog monocular OKN: involvement of pretectal GABAergic and cholinergic systems. AB - The frog horizontal monocular optokinetic nystagmus (OKN) is asymmetrical, the temporal-nasal (T-N) stimulation being the sole stimulation efficient to evoke the reflex, the nasal-temporal (N-T) component being almost absent. Coil recordings showed that, in adult animals, prolonged monocular visual deprivation by unilateral eyelid suture provoked the appearance of the N-T component. The OKN became symmetrical, reacting for both directions of stimulation. Microinjection of either gamma-aminobutyric acid (GABAA) agonist 4,5,6,7-tetrahydroisoxazolo (5,4-C) Pyridin-3-ol (THIP) or muscarinic cholinergic antagonist atropine into the nucleus lentiformis mesencephali, the pretectal mesencephalic structure involved in OKN, transiently abolished the presence of N-T component. This result suggests that the phenomenon of visual plasticity, occurring after a week of monocular deprivation, can be due, at least partially, to reduction in pretectal GABAergic inhibition, and to concomitant activation of cholinergic muscarinic receptors. PMID- 1584461 TI - Craniovascular nociceptive pathways relay in the upper cervical spinal cord in the cat. AB - Units in the dorsolateral area of the upper cervical cord and the ventroposteromedial nucleus of the thalamus respond to stimulation of cranial vessels. To study the physiological role of the upper cervical cord in craniovascular transmission, we used a cryoprobe to interrupt reversibly neural transmission through the cord while recording in the thalamus. Twenty-one of 47 thalamic units tested showed reversible diminution in their response to superior sagittal sinus stimulation during cervical cord cooling. In contrast, receptive field responses and spontaneous thalamic activity were unaffected. These data suggest offt the cervical cord relays craniovascular nociceptive afferents. PMID- 1584462 TI - Administration of carbachol into the lateral ventricle and suprachiasmatic nucleus (SCN) produces dose-dependent phase shifts in the circadian rhythm of locomotor activity. AB - The cholinergic agonist, carbachol, induces phase-dependent shifts in the timing of the circadian rhythm of locomotor activity (CRLA). The effects of carbachol injections into the lateral ventricles of hamsters were compared between circadian times that produce phase delays vs. phase advances in the CRLA. The shape of the dose-response curves and the ED50 for carbachol injections were similar for the two injection times. The second experiment demonstrated the dose dependence of phase advances produced by carbachol injections into the area of the suprachiasmatic nucleus. These results indicate that carbachol exerts similar dose-dependent actions for both phases advances and phase delays. PMID- 1584464 TI - Pathological changes in the brain of a patient with familial Alzheimer's disease having a missense mutation at codon 717 in the amyloid precursor protein gene. AB - The brain of a 61-year-old patient with familial Alzheimer's disease, showing a missense (valine----glycine) mutation at codon 717 of the amyloid precursor gene, has been examined at postmortem. Sections of brain showed pathological features entirely typical of Alzheimer's disease with no unusual characteristics. It seems therefore that this particular mutation is indeed pathogenic and that the altered amyloid precursor protein resulting from expression of this mutation is processed in a way that triggers or promotes the pathological cascade of Alzheimer's disease. PMID- 1584463 TI - Familial Alzheimer's disease with the amyloid precursor protein position 717 mutation and sporadic Alzheimer's disease have the same cytoskeletal pathology. AB - The cytoskeletal pathology of a patient with familial Alzheimer's disease (AD) associated with the probably causal amyloid precursor protein (APP) codon 717 Val ---Ile mutation is described. In addition to moderately extensive beta A4 protein deposition within the substance of the brain and in blood vessel walls (congophilic angiopathy), there was abundant cytoskeletal pathology in the form of neurofibrillary tangles, plaque neurites and neuropil threads. Interestingly, plentiful cortical and subcortical Lewy bodies were also seen. In order to compare the cytoskeletal pathology in this case with that seen in sporadic cases of AD we (1) studied the immunohistochemical profile of the amyloid and cytoskeletal pathology with antibodies to beta A4 protein, tau, phosphorylated neurofilament epitopes and ubiquitin and (2) performed a biochemical fractionation and Western blot analysis for the abnormally phosphorylated form of tau (A68) characteristically seen in AD. No substantial difference between the familial case and sporadic cases could be found. We conclude that it is now reasonable to hypothesise that an abnormality in APP metabolism is responsible not only for the deposition of beta A4 protein, but also for the range of cytoskeletal pathology, typical of AD. PMID- 1584465 TI - Effects of systemic ethanol on medullary vasomotor neurons and baroreflexes. AB - The acute effects of systemic ethanol on reticulospinal sympathoexcitatory neurons were examined in vivo in anesthetized, paralyzed rats. Ethanol (0.45 g/kg, i.v.) potentiated the depressant effect of locally applied gamma aminobutyric acid (GABA) but attenuated the excitatory effect of L-glutamate. The baroreflex-mediated inhibition of these neurons and sympathetic nerve activity were partially depressed by the agent while aortic nerve activity and its sensitivity to changes in arterial pressure were not altered. These results suggest that systemic ethanol may markedly influence cardiovascular function by interfering in medullary GABAergic and glutamatergic transmissions involved in central control of the cardiovascular system. PMID- 1584466 TI - Fine structure of nerve processes containing basic fibroblast growth factor in muscle spindles of the rat masseter muscle. AB - An antiserum against basic fibroblast growth factor (bFGF) was characterized by immunoblot analysis and used to investigate the fine structure of bFGF-containing processes in muscle spindles of the rat masseter muscle. The bFGF antiserum recognized purified bFGF and bFGF-like materials with the same molecular weight as bFGF in crude homogenate of the brainstem from which bFGF fibers in the masseter muscle spindles presumably originate. Immunoelectron micrographs demonstrated that both proprioceptive and motor nerve endings in contact with intrafusal fibers contain bFGF. These findings suggest that bFGF of central (possibly trigeminal mesencephalic and motor nucleus) origin is transported into the muscle spindles subserving mechanoreception. PMID- 1584467 TI - Blood flow increases in the skin of the anaesthetized rat that follow antidromic sensory nerve stimulation and strong mechanical stimulation. AB - In anaesthetized rats, punctate pressure using forces greater than or equal to 20 mN caused small transient rises in skin blood flow that were similar in normally innervated and chronically denervated skin. A force of 11 mN, sufficient to excite most C-fibres of the polymodal nociceptor class, failed to cause vasodilatation. Following short periods of low frequency electrical stimulation of the saphenous nerve at C-fibre strength, larger increases in blood flow ('antidromic vasodilatation') were seen. Antidromic vasodilation was unaffected by high frequency stimulation of A alpha beta axons or by simultaneous innocuous mechanical stimulation. The failure of pressure at levels suprathreshold for C fibre nociceptors to cause neurogenic vasodilatation may mean that antidromic vasodilation in rat skin is due to activity restricted to a mechanically insensitive sub-population of C-fibres. PMID- 1584468 TI - Difference in glossopharyngeal and phrenic inspiratory activities of rats during hypocapnia and hypoxia. AB - Inspiratory (I) activities of glossopharyngeal (IX) and phrenic (Phr) nerves were compared during hypocapnia or hypoxia in the urethane anesthetized and carotid deafferented rat. Hypoxic or hypocapnic suppression of I activity was smaller in the IX than in the Phr nerve. A small ramp like rhythmic IX activity was seen even in the absence of Phr discharge during hypocapnia or hypoxia. Respiratory rhythmicity may be better recognized by IX motoneuron activity during suppression by altered chemical stimuli. PMID- 1584470 TI - The strategy of empowerment. PMID- 1584469 TI - Nurse empowerment is a concept incorporated in autonomy and professional accountability. PMID- 1584471 TI - The myth of empowerment. PMID- 1584472 TI - Staff nurse empowerment. PMID- 1584473 TI - The clinical nurse specialist and empowerment: say goodbye to the fairy godmother. PMID- 1584475 TI - On the scene: nurse empowerment for the 21st century. PMID- 1584474 TI - The road to empowerment. PMID- 1584476 TI - Caring: a key to empowerment. PMID- 1584477 TI - Interactive planning: a model for staff empowerment. PMID- 1584478 TI - Staff nurse empowerment: current status and future projections. PMID- 1584479 TI - Leadership skills for empowerment. PMID- 1584480 TI - The source and process of empowerment. PMID- 1584481 TI - Leadership, nurses, and patient satisfaction: a pilot study. PMID- 1584482 TI - Managing pulmonary patients. PMID- 1584483 TI - John's best. PMID- 1584484 TI - Evaluating C-reactive protein levels. PMID- 1584485 TI - Reviving your career dream. PMID- 1584486 TI - Refusing unreasonable requests. PMID- 1584487 TI - Making education affordable. PMID- 1584488 TI - Ring of regret. PMID- 1584489 TI - Nursing's unseen rewards. PMID- 1584490 TI - Reversing methemoglobinemia. PMID- 1584491 TI - Learning to live with congestive heart failure. PMID- 1584492 TI - No need to clarify order. PMID- 1584493 TI - Predictions for critical care nursing. PMID- 1584494 TI - The view from the mattress. PMID- 1584495 TI - Using cardiac leads the right way. PMID- 1584496 TI - New drugs. PMID- 1584497 TI - Mrs. Hixon was more than "the C.V.A. in 251". PMID- 1584498 TI - When your medical/surgical patient is also mentally ill. PMID- 1584499 TI - The nurse who listened. PMID- 1584500 TI - A round of applause. PMID- 1584501 TI - Teaching caregivers about Alzheimer's disease. PMID- 1584502 TI - Discuss advance directives. PMID- 1584503 TI - Myths & facts ... about non-Q-wave myocardial infarction. PMID- 1584504 TI - The unsung shapers of nursing science. PMID- 1584505 TI - Search in research. PMID- 1584506 TI - Nursing knowledge and human science: ontological and epistemological considerations. AB - This article examines the meaning of human science in relation to extant nursing knowledge. The origins of the human science tradition are traced to the philosopher Wilhelm Dilthey, who challenged the dominance of the positivist perspective for generating knowledge of the human lifeworld. Specific ontological and epistemological criteria for human science are proposed. Four nursing frameworks, Paterson and Zderad's humanistic nursing, Newman's model of health as expanding consciousness, Watson's human science and human care, and Parse's theory of human becoming, are found to have consistencies and inconsistencies with the human science tradition. It is proposed that the human science perspective is present in and will continue to be reflected in the evolution of nursing science. PMID- 1584507 TI - Derivation and testing of tenets of a theory of social organizations as adaptive systems. AB - Management and organizational theories are commonly used to design nursing administration studies. This article proposes a nursing theory as a viable alternative and demonstrates its utility in the conduct of nursing administration research. The purpose of the research was to determine the explanatory power of the environmental stimuli of medical condition, nursing condition, nursing intensity, and medical severity on length-of-stay (LOS). Twenty-three percent of the variance in LOS was accounted for by the environmental stimuli with nursing acuity contributing 14%. The focal stimulus, medical condition (diagnosis-related groups), uniquely explained only one percent of the variance. The theory of social organizations as adaptive systems, derived from the Roy adaptation model, provides an attractive nursing framework to guide and design studies that will contribute to nursing administration science and address practical problems confronting nurse administrators. PMID- 1584508 TI - The consciousness rainbow: an explication of Rogerian field pattern manifestations. AB - The consciousness rainbow is a heuristic designed to be used in nursing practice in conjunction with the personalized nursing practice model based on Rogers' science of unitary human beings (Rogers, 1970, 1990). The first phase in practicing nursing is pattern manifestation appraisal, followed by deliberative mutual patterning. This article presents pattern manifestation appraisal by describing patterns associated with "being," "well-being," and "not being." Clients who enter well-being via another dimension are encouraged to experience "being" in the present as a step toward genuine well-being. PMID- 1584510 TI - Introducing a univariate method to analyze multivariate data with two groups. PMID- 1584509 TI - Alternative approaches to nursing practice: application of Peplau, Rogers, and Parse. AB - This article demonstrates three major nursing theories in practice. The uniqueness of each theory is clarified through the presentation of nursing formulations and practice implications. The discussion provides a metaperspective of how practice based in nursing theory is different from traditional practice and how nursing theory can guide practice. PMID- 1584511 TI - Different forms of caring communion. PMID- 1584512 TI - To be a nurse. PMID- 1584514 TI - Practice partners: humanizing healthcare. PMID- 1584513 TI - Criminal liability for the nurse--Part II. PMID- 1584515 TI - Understanding your operating system. PMID- 1584516 TI - Nursing management and JCAHO. American Organization of Nurse Executives. AB - JCAHO is one example of a powerful standards organization whose influence touches the daily lives of nursing managers, and some of whose programs are influenced by the efforts of nursing representatives and nursing organizations. The presence of accomplished nurse executives at the JCAHO strengthens the entire accreditation process for healthcare facilities. Oftentimes, these appointments are brought about through the advocacy, lobbying, and liaison efforts of national nursing organizations working together to ensure that nursing's perspective is heard and understood throughout the standards process. PMID- 1584517 TI - Tuberculosis: it's back. PMID- 1584518 TI - Multiattribute utility theory in decision-making. PMID- 1584519 TI - First-line manager compensation: the missing piece. PMID- 1584520 TI - Cost/benefit analysis of cardiopulmonary resuscitation: a comprehensive study- Part II. PMID- 1584521 TI - Methods of evaluating turnover costs. PMID- 1584522 TI - Nursing process in telephone advice. PMID- 1584523 TI - A med/surg nursing record: convenient, adequate--and accepted. PMID- 1584524 TI - Of commissions, omissions and just plain missions. PMID- 1584525 TI - Stop re-inventing the wheel: textbooks as procedure manuals. PMID- 1584526 TI - Teamwork: administrators on evening duty. PMID- 1584528 TI - Nursing hours: impact of escort activities. PMID- 1584527 TI - Why are RNs continuing to cosign for ward clerks? PMID- 1584529 TI - Can community hospitals afford a CNS? PMID- 1584530 TI - Superstar: model leader or model member. PMID- 1584531 TI - Inpatient nurse practitioner: to be or not to be? PMID- 1584532 TI - A high-risk perinatal nurse practitioner program. PMID- 1584533 TI - PROM: where a little movement means a lot.... PMID- 1584535 TI - Digging for solutions. PMID- 1584534 TI - Job satisfaction through self-scheduling. PMID- 1584536 TI - Setting up an autologous bone marrow transplant program. PMID- 1584537 TI - Pediatric gynecologic imaging. AB - Ultrasonography is the initial examination of choice for evaluation of pediatric gynecologic disorders, with computed tomography and magnetic resonance used as secondary tests to verify an abnormality or to determine the extent of disease. The spectrum of gynecologic diseases in childhood and adolescence and their imaging characteristics are reviewed. PMID- 1584538 TI - Dysfunctional uterine bleeding. AB - DUB is a common adolescent problem usually related to HPO axis immaturity and anovulation. Modern hormonal and other medical therapies enable physicians to treat DUB effectively, regardless of the cause. The evaluation provides the physician with an opportunity to offer confidential education, reassurance, treatment, and appropriate intervention in cases in which a systemic or coagulation disorder may be the underlying pathophysiology involved. PMID- 1584539 TI - Expressive therapy in pediatric and adolescent gynecology. AB - Children and adolescents seen by gynecologists may have a broad spectrum of emotional needs that can affect the gynecologic examination as well as the young person's overall well-being. The field of expressive therapy is a relatively new one. The therapist uses a variety of techniques to allow the patient to explore feelings, attitudes, or events in ways that may help the patient to develop new strategies to cope with distress. The application of expressive therapy in pediatric and adolescent gynecology appears to be ever more encompassing. PMID- 1584540 TI - Adolescent sexuality and issues in contraception. AB - The influence of physiologic, psychologic, and cultural influences on human sexuality is reviewed. These factors are considered in the exploration of how adolescents express their sexuality and the consequences of that expression. PMID- 1584541 TI - Child sexual abuse. AB - It is estimated that the number of child victims of sexual assault is in excess of 200,000 per year. Many of these children are brought to emergency room facilities or to their private physician's office for evaluation. The recent advances in the area of diagnosis and management of children who are the victims of sexual abuse are presented. PMID- 1584542 TI - Psychological sequelae of sexually transmitted diseases in adolescents. AB - Sexually active adolescents are the highest risk group for many of the sexually transmitted diseases. Although clinical presentations, diagnostic methods, and medical sequelae are understood increasingly, psychological sequelae are often neither recognized nor understood. Insight into these issues may prevent repeat episodes of sexually transmitted diseases and limit their spread. This article summarizes the literature regarding psychological issues and sequelae and emphasizes the need for further study. PMID- 1584543 TI - Gynecologic examination of the teenager and young child. AB - The gynecologic examination of the child or adolescent need not be trying to the patient or the physician. Patience, awareness of the patient's need to be treated with respect and honesty, and knowledge of a few modifications to the adult technique will allow a helpful examination in almost all cases. The final objective should always be to promote the gynecologic health of the patient, and this is best accomplished if she leaves the physician's office with a positive reinforcement of her self-esteem, and her ability to participate in her own health care. PMID- 1584544 TI - Prepubertal vulvovaginopathies. AB - The vast majority of prepubertal gynecologic problems fall into three categories. The most serious category includes those "things that bleed": sarcoma botryoides, trauma (including sexual abuse), vaginal foreign objects, condylomata, urethral prolapse, and single organism vaginitis. Very rarely, the clinician will see precocious menarche, metastatic Crohn's disease, vascular vulvar lesions, and factitious cases. The next category contains entities that have an abnormal appearance: ambiguous genitalia, periurethral cysts of the newborn, hymenal variants, and agglutination of the labia and vulva. Rarely, an underlying skin disorder such as lichen sclerosus, seborrhea, or atopic vulvitis will be seen. The last and most bothersome category, distinguished by its symptoms of pruritus and discharge, includes the most common types of vulvovaginitis. PMID- 1584545 TI - Aberrant puberty. AB - With the emergence of an understanding of the processes at the cellular level that control the differentiated functions of tissues and eventually manifest as the developmental sequence in the whole animal, it is possible to describe pubertal aberrations in terms that are at once grounded in fundamental concepts of cellular biology and of practical value to the clinician. Delayed puberty and its treatment represent a relatively straightforward problem, submitting to division into two groups of patients: those whose gonadotropin levels are elevated (hypergonadotropic hypogonadism), implying primary gonadal failure; and those whose gonadotropin levels are low (hypogonadotropic hypogonadism), implying either a failure of the central control axis or an adaptive response to a disruptive stress. Precocious puberty is also usefully separable into two distinct groups of patients: those in whom the normal central control axis is activated and those in whom it is not. The workup beyond the basic general stage and the approach to therapy are both determined by into the group into which the patient can be assigned. Advances in imaging technology have enhanced the diagnostic process, and chemical remodeling of the hypothalamic peptide, which mediates control of the pituitary's contribution, has revolutionized the treatment of CMPP, making it imperative that the clinician be able to distinguish those conditions that merit treatment from those that may be observed safely. PMID- 1584546 TI - Hyperandrogenism in the adolescent. AB - Problems of hyperandrogenism are becoming increasingly recognized in the female adolescent. Manifestations of androgen excess can have both far-reaching metabolic implications and significant effects on body image. At a crucial time in personality development, these problems should not be taken lightly. A common pathophysiology associated with androgen excess is PCOS. Awareness of this fascinating syndrome and its metabolic implications can alert health-care professionals so that the adolescent's metabolic, physical, and psychological needs are best addressed. Individualization of treatment is the rule. Team approaches to the diagnosis and treatment of the disorder have proven effective in reversing pathophysiology that has led to hirsutism. PMID- 1584547 TI - Diagnostic considerations in breast disorders of children and adolescents. AB - A review of the medical literature on breast disorders in children and adolescents leads to a number of conclusions. Though females may develop breast masses early in life, the risk of malignancy is extremely low. Therefore, most breast masses in the young can be managed conservatively without surgery. Breast masses in young girls may represent thelarche or tumors of adjacent structures, but are unlikely to be malignant. The most common form of bilateral breast enlargement in prepubertal girls is premature thelarche, a benign, transient, and incomplete form of precocious puberty. Fibroadenoma is the most common cause of breast mass in female adolescents. In the rare case in which a breast mass in this population is malignant, it is more likely to be a noncarcinomatous or metastatic cancer. Because of the low risk of malignancy and the relatively different composition of the adolescent as compared to the adult breast, mammography is not recommended for routine screening or routine imaging of breast masses in adolescents. The role of breast self-examination should be further studied. PMID- 1584548 TI - Flicker electroretinograms: a systems analytic approach. AB - We observed multiple maxima and minima in the electroretinogram (ERG) first harmonics which varied as a function of adaptation level, mean illuminance, and modulation depth. Based on differences in response characteristics we identified a minimum of 3 parallel mechanisms operating at 3 frequency regions within the ERG: a low frequency region (less than 10 Hz), a midfrequency region (centered near 20 Hz), and a high frequency region (centered near 40 Hz). The low frequency region was observed both in dark- and light-adapted conditions, was basically linear, and showed nonlinear behavior only at high contrasts in either light or dark adaptation. It may be modeled as a low pass filter. The midfrequency region was clearly observed only above cone threshold, was nonlinear at low contrasts, and may be modeled as a linear filter followed by an essential nonlinearity. The high frequency region was observed under high levels of light adaptation and also was nonlinear at low contrast. It may be modeled also as a linear filter followed by an essential nonlinearity. PMID- 1584549 TI - A posteriori digital filtering to reduce signal-averaging of steady-state evoked potentials. AB - This paper describes a signal extraction technique that involves taking the time series representation of signals, transforming them into the frequency domain, determining the chance occurrence of power at each frequency, and filtering accordingly. An inverse Fourier transform is then used to recreate the new time domain representation, which has been appropriately filtered for extraneous noise. Thus, this technique involves a posteriori digital filtering based on a statistical criterion for component inclusion. Computer simulation indicated that, at poor signal-to-noise ratios and with fewer samples, this technique is 5 to 10 times better at signal extraction than conventional signal averaging. Examples of pattern-elicited electroretinograms (PERG's) are used to illustrate the efficacy of this method. PMID- 1584550 TI - The human pattern ERG: alteration of response properties with aging. AB - The influence of aging on both the amplitude and the latency of transient and steady-state pattern electroretinograms (PERG's) was studied in 80 healthy participants ranging from 25 to 77 years of age (mean age, 55.3 years). Responses to counterphasing checkerboard patterns were recorded for each of 7 test conditions in which the spatial (i.e., check sizes 0.25, 0.50, 1.00, and 2.00 degrees) and temporal characteristics (i.e., counterphasing at either 2, 4, 8, or 16 rps) of the stimuli were varied. For both the transient and steady-state PERG's amplitude was inversely related to age (p less than 0.05 for each test condition). In general, PERG latency directly correlated with age, but this effect was less robust (p less than 0.05 for one transient condition and three of the four steady-state conditions). The influence of age on the spatial tuning of the PERG was minimal; the decrease in PERG amplitude and the increase in PERG latency as a function of age were essentially the same for all test conditions. However, the magnitude of the age-related reduction in PERG amplitude was observed to vary with temporal frequency, being largest for the steady-state condition (16 rps). The results from an experiment in which young subjects were tested while wearing opaque contact lenses with 2-mm artificial pupils suggest that senile miosis is a significant factor contributing to the age-related PERG amplitude and latency changes, but it does not fully account for the observed changes. PMID- 1584551 TI - The Julius F. Neumueller Award in Optics, 1989: change of pupil centration with change of illumination and pupil size. AB - Pupil centration is important to the optical blur on the retina. Using a dual Maxwellian view system we measured the centration of the pupil with respect to the achromatic axis of the eye as a function of pupil size. Significant shifts of the pupil center (up to 0.6 mm) with pupil dilation were measured in both nasal and temporal directions. The effect was usually symmetrical between the two eyes and the shift was linear with pupil size in one-half of the subjects. From their initial positions the linear pupil center shifts with dilation were in the direction of the achromatic axis. PMID- 1584552 TI - Computerized Arden grating technique for the measurement of the contrast sensitivity function. AB - We developed a computerized contrast sensitivity function (CSF) measurement technique using a computer graphics board to reproduce Arden grating type stimuli. The reliability of the procedure was examined by evaluating the standard deviation of repeated test differences. The validity of the procedure was tested by comparison with both a manual method of adjustment technique and with Regan low contrast letter charts. The procedure has been performed at a number of exposure speeds to account for the effect of reaction time and attention of the results. The optimum exposure time for the procedure has been found to be greater than or equal to 22 s. As a result of the benefits of automation the test is quick, produces test-retest correlation coefficients for the five spatial frequencies tested which are similar to those for the method of adjustment procedure (0.76 to 0.91 for the computerized test, 0.66 to 0.88 for the signal generator measurements), and produces values which correspond closely with the method of adjustment measurement. It has the advantages of utilizing hardware already available in many computer systems, having a constant mean luminance across the screen, and having a constant and optimized presentation time. PMID- 1584553 TI - Genetics of dyseidetic dyslexia. AB - The nine pedigrees presented here suggest an autosomal dominant mode of transmission for the dyseidetic type of dyslexia. Sex-influence probably accounts for the high male to female ratio. Other modes of transmission are highly unlikely for dyseidesia but possible for other types of dyslexia, with the multifactorial mode being most likely. Genetic counseling is particularly feasible in cases of dyseidetic dyslexia. PMID- 1584554 TI - Normal values of eye position in the Chinese population of Hong Kong. AB - Exophthalmos, interpupillary distance (IPD), interobital distance (IOD), and inner intercanthal distance (ICD) were measured in an adult Chinese population from Hong Kong (HKC). Mean values and normal range for 95% of the population were determined and the relation with head size and body height examined. Values of exophthalmos and IPD in our Chinese population were similar to those given for Caucasian groups. IOD and ICD were larger in the Chinese than in adult Caucasians. Our findings show generally larger values in the HKC than has been found for other populations in mainland China. PMID- 1584555 TI - Relation between meridional power and the dioptric power matrix. AB - The components of meridional power in any meridian can be expressed elegantly in terms of the dioptric power matrix. The form of the expressions is that which is well known in the statistical literature as a quadratic form; there are important statistical implications for dioptric power and its measurement. The relation forms the basis of the calculation and least-squares estimation of dioptric power and surface curvature from meridional measurements. PMID- 1584556 TI - Is emmetropization a scale artifact? PMID- 1584557 TI - Statistics notebook: entry III.G: power of a test. PMID- 1584558 TI - Improving the diagnostic power of electroretinography by transient alteration of the ocular perfusion pressure. AB - In this report we present the results of a series of studies focusing on the effects of transient changes in the ocular perfusion pressure (OPP) on retinal function in normals as assessed by the flash electroretinogram (ERG). A transient increase or decrease in the OPP affected by body inversion and compression/suction ophthalmodynamometry (ODM), respectively, is shown to affect differentially the b-wave of scotopic and photopic ERG's. However, under dark adapted conditions, the cone component of the red flash ERG b-wave exhibited a vulnerability to decreased OPP which approached that seen for the b-wave of the scotopic blue flash ERG b-wave. Similar test procedures used to investigate the functional response of the inner plexiform layer during altered OPP revealed component-specific changes in white flash scotopic oscillatory potentials (OP's). The results of these provocative tests of retinal function offer new insights into basic retinal physiology and encouraging prospects for practical clinical diagnostic procedures with enhanced sensitivity and specificity for subclinical retinal disorders. PMID- 1584559 TI - Analysis of nonlinearities in the flicker ERG. AB - The electroretinogram (ERG) response to steadily flickering fields shows significant nonlinear components. These nonlinear components have been used to investigate the ERG. We find the following. (1) The fundamental retinal response can be recorded at frequencies greater than 100 Hz and the second and higher harmonic responses have measurable response frequencies as high as 200 Hz. Both the fundamental response component and the second harmonic response component have multiple local maxima as a function of frequency. (2) Measurement of the response of the retina to the sum of two sine waves indicates that there is an early low-pass temporal filter in the retina. This early filter has a cutoff frequency between 40 and 50 Hz. (3) The high frequency nonlinearity is not a compressive nonlinearity. PMID- 1584560 TI - Autoregulation and glaucoma. PMID- 1584561 TI - Blurring after iridotomy. PMID- 1584562 TI - Nerve sheath decompression in patients with functioning shunts. PMID- 1584563 TI - Intravitreal penetration of oral ciprofloxacin in humans. AB - Nineteen patients about to undergo elective vitreous surgery received 1 oral dose of 750 mg of ciprofloxacin before surgery. Specimens of serum and vitreous were collected 90 minutes to 18 hours after drug administration and were assayed for antibiotic content with a microbiologic disk agar technique. From 4 hours and 50 minutes to 16 hours and 50 minutes after a single oral dose, ciprofloxacin reached intravitreal levels above its minimal inhibitory concentration for 90% of Staphylococcus epidermidis, Bacillus species, and Enterobacteriaceae. However, intravitreal levels never exceeded the MIC90 for Staphylococcus aureus and Pseudomonas. PMID- 1584565 TI - Management of giant retinal tears without scleral buckling. Use of radical dissection of the vitreous base and perfluoro-octane and intraocular tamponade. AB - The introduction of intraoperative perfluorocarbon liquids in the management of giant retinal tears has allowed exact anatomic reapposition of the retina and the giant retinal tear. Therefore, the authors managed 11 eyes with giant retinal tears and no proliferative vitreoretinopathy without scleral buckling. Maximum removal of the basal vitreous gel was performed in all cases, and perfluoro octane was used intraoperatively to unfold the inverted posterior flap and reattach the retina completely. Endophotocoagulation was applied to the edges of the tear and perfluoropropane or silicone oil was used as an intraocular tamponade. Although 1 eye required reoperation for a redetachment from posterior proliferative vitreoretinopathy, all retinas were reattached with final visual acuity of 5/200 or better in 9 eyes. Eight additional major procedures were necessary in seven eyes: removal of silicone oil in four (with removal of perisilicone proliferation in three), repeat vitrectomy and membrane removal with photocoagulation twice in one eye, cataract extraction in one eye, and removal of a macular pucker in one eye. Four eyes required postoperative fluid-gas exchange and three eyes had tissue plasminogen activator injections into the anterior chamber for postoperative fibrin reactions. PMID- 1584564 TI - Propionibacterium acnes endophthalmitis after intracapsular cataract extraction. AB - The authors report a case of Propionibacterium acnes endophthalmitis after intracapsular cataract extraction with implantation of an anterior chamber intraocular lens. The patient's chronic inflammation persisted for 5 years after cataract surgery despite treatment with pars plana vitrectomy, intraocular lens removal, topical and oral steroids, and topical fortified antibiotics. Fluctuations in the inflammation were paralleled by changes in the size and appearance of a white plaque on the posterior corneal surface. Anterior chamber tap cultures were positive for P. acnes after 8 days of incubation under anaerobic conditions. The inflammation was not controlled until the posterior corneal plaque, which was the presumed nidus of the chronic infection, was removed and the patient was treated with intravitreal and oral antibiotics. PMID- 1584566 TI - Effect of buckling material on ocular rigidity. AB - Enucleated human eyes were banded with metal and silicone bands to produce reductions in their diameter of 2 mm and 4 mm. The ocular rigidity produced by each banding material at each diameter was measured in the pressure range of 10 mmHg to 40 mmHg. Metal bands produced mild reductions in ocular rigidity that were significantly (P less than 0.05 to 0.01) lower than the control ocular rigidities in some pressure ranges. Silicone bands produced large reductions in ocular rigidity that were significantly (P less than 0.01) lower than ocular rigidities observed in metal-banded or control conditions in all pressure ranges. The influence of the elastic silicone banding material on ocular rigidity was greater than the influence of altered shape and wall stress that occurred with metal banding. PMID- 1584567 TI - Risk factors for retinal vein occlusions. A case-control study. AB - The authors conducted a case-control study of risk factors for retinal vein occlusions using 87 patients with vein occlusions, chosen randomly from photographic files from their institution between 1985 and 1990, and a control group of 85 subjects 38 years of age (the youngest individual in the vein occlusion group) or older, who were randomly selected from the records of two general ophthalmologists in the authors' department. Certain risk factors for retinal vein occlusion were highly significant when subjects with retinal vein occlusion were compared with the control group. These risk factors included systemic hypertension (odds ratio [OR], 3.86; 95% confidence interval [Cl], 2.08 to 7.16), open-angle glaucoma (OR, 2.89; 95% Cl, 1.38 to 6.05), and male sex (OR, 2.61; 95% Cl, 1.43 to 4.79). Race, presence of diabetes mellitus, history of coronary artery disease or stroke, and family history of diabetes, glaucoma, coronary artery disease, or stroke were not significant risk factors in the population studied. Logistic analysis of the risk factors showed no interactions. Risk factors for branch retinal vein occlusion and central retinal vein occlusion were identical. PMID- 1584568 TI - Tissue plasminogen activator thrombolysis during surgical evacuation of experimental subretinal hemorrhage. AB - To assess the role for intraoperative thrombolysis during surgical evacuation of massive subretinal hemorrhage, the authors studied the ability of tissue plasminogen activator (tPA) to facilitate removal of an experimental subretinal blood clot through a small drainage retinotomy. In rabbit eyes, a single subretinal injection of tissue plasminogen activator in concentrations of up to 250 micrograms/ml failed to produce significant (greater than 50%) clot dissolution during a 3-hour period. However, repetitive subretinal lavage and aspiration with tPA (50 micrograms/ml) resulted in progressive intraoperative clot dissolution in rabbits and allowed complete evacuation of blood through a small drainage retinotomy in 6 (100%) of 6 cat eyes. Repetitive vigorous subretinal irrigation with saline solution had no discernible effect on clot size in rabbit eyes. Histopathologic examination of cat eyes following tPA-assisted surgical evacuation of subretinal blood showed preservation of the outer retina in 2 eyes and severe atrophy of the outer retina in 4 eyes. PMID- 1584569 TI - Combined amplitude and phase criteria for evaluation of macular electroretinograms. AB - Focal electroretinograms (ERGs) were obtained from 35 normal eyes and 48 eyes with known macular disease using the MaculoScope stimulator-ophthalmoscope instrument. Response amplitude and phase were combined to permit interpretation of the ERG responses as two-dimensional vectors. This vector interpretation avoids statistical anomalies and distortions inherent in the use of amplitude and phase response parameters. Furthermore, the vector interpretation permits the use of the Hotelling T2 statistic for the assessment of the significance of the differences between ERG responses, providing greater statistical power than simultaneous comparison of amplitude and phase data separately. The distribution of normal responses yielded limiting normal values of 135 nV for the amplitude and -95 degrees for the phase lag of the focal ERG as recorded by the MaculoScope instrument. Significant abnormalities of the focal ERG are illustrated for cases of cilioretinal artery occlusion, Stargardt's disease, idiopathic macular hole, diabetic macular edema, and idiopathic macular dysfunction with normal fundus. This study demonstrates the potential value of the focal ERG in the demonstration of macular disease undetectable by conventional electroretinography. PMID- 1584570 TI - Calf lung surfactant extract prophylaxis and retinopathy of prematurity. AB - Retinopathy of prematurity (ROP) is an important cause of blindness among extremely low birth weight infants (birth weight less than or equal to 1000 g). In the 1990s, greater numbers of extremely low birth weight infants will survive, in part due to routine surfactant replacement therapy for neonatal respiratory distress syndrome. Few studies have evaluated the effect of surfactant therapy on the incidence and severity of ROP. The authors performed a review of the records of extremely low birth weight infants born in two 2-year intervals before and after initiation of a clinical protocol in which all extremely low birth weight infants received prophylactic treatment with calf lung surfactant extract (Infasurf). Surfactant therapy was associated with a significant improvement in survival to discharge (79% [88 of 112] versus 63% [82 of 131]; P = 0.01). Compared with control infants, surfactant-treated infants had a significantly lower incidence of any stage of ROP (64% [56 of 87] versus 85% [68 of 80]; P less than 0.004). The incidence of threshold (Stage 3 plus or greater) ROP was substantially reduced (3.4% [3 of 87] versus 10% [8 of 80]; P = 0.16)). The surfactant-associated reduction in ROP was independent of birth weight, gestational age, race, or sex. These data suggest that Infasurf may substantially reduce the incidence and severity of ROP in the extremely low birth weight population. PMID- 1584571 TI - Smoking and the risk of early metastases from uveal melanoma. AB - Smoking is suspected of altering host immunity and may therefore hasten the development of metastases among cancer patients. The authors followed 946 patients with melanomas of the choroid and/or ciliary body who had been treated with proton beam irradiation and who had provided a smoking history during their evaluation before treatment. After a mean follow-up of 33 months, 98 patients were diagnosed with metastatic disease. Metastasis-free survival rates 3 years after irradiation were similar in association with never, past, and current cigarette smoking (86%, 89%, and 90%, respectively; P = 0.90). Rates also were similar with increasing pack-years of exposure and when the product smoked was cigarettes versus pipes or cigars only. Estimates for smoking effects were unchanged after adjusting for established prognostic factors for metastases. Results suggest that smoking does not alter the risk of metastases during the first few years after irradiation of choroidal melanomas. PMID- 1584572 TI - Management of the subluxed crystalline lens. AB - There has been a traditional reluctance to remove a subluxed (ectopic) lens because of the high surgical risk. The use of closed intraocular microsurgical techniques, however, now allows greater intraoperative control with few complications. The authors present the results of subluxed lens extraction, by limbal or pars plana lensectomy, in 44 eyes of 24 patients, in which the indication for surgery was lens subluxation causing a reduction in visual acuity or uncorrectable refractive error. Visual acuity was improved in all cases after surgery, with no significant complications. Patients with reduced visual acuity secondary to ectopic lenses have a good visual prognosis after lensectomy using a closed intraocular microsurgical technique. PMID- 1584573 TI - Prevalence of age-related lens opacities in a population. The Beaver Dam Eye Study. AB - Age-related lens opacities are common and are a frequent cause of loss of vision. The Beaver Dam Eye Study was designed to estimate the prevalence and severity of lens opacities in a rural community in the United States. Adults between the ages of 43 and 84 years, identified by private census, were examined and participated in the study (n = 4926). Photographs were taken of the lenses and were graded in masked fashion according to a standardized protocol. For nuclear sclerosis, more severe levels occurred more commonly in older age groups and in women. Overall, 17.3% had nuclear sclerosis more severe than level 3 in a 5-step scale of severity. Cortical opacities increased with increasing age and were more common in women. They were found in 16.3% of the population. Posterior subcapsular opacities occur in 6.0% of the population. There was a significant trend of greater prevalence at older ages, but no sex effect. The frequency of early cataract increased in both sexes through the age group 65 to 74 years, but declined in those 75 years of age and older. The frequency of late cataract increased consistently with age. Women were more severely affected than men. This study confirms that lens opacities are common in adults in the United States. These data are important for providing for social and health care needs. It is important to determine causes of cataracts in order to develop preventive programs. PMID- 1584574 TI - Complex orbital fracture repair using rigid fixation of the internal orbital skeleton. AB - Large orbital fractures involving more than one orbital wall are frequently associated with enophthalmos and vertical globe dystopia. The authors repaired 22 orbits in 20 patients using the technique of rigid fixation of the internal orbital skeleton. Eleven orbits were reconstructed with titanium or vitallium implants that were custom-shaped to span the bony defect and fixed to the orbital rim. Seven orbits were reconstructed with bone grafts rigidly supported by a miniplate, and, in four cases, direct lag screw support of bone grafts was used. The intraoperative goal was to restore the native orbital anatomy and volume. Autologous calvarial bone grafts were used to supplement the repair to achieve the desired volumetric effect and to cover additional wall defects. A reoperation for additional orbital augmentation was needed in one enophthalmic and one anophthalmic orbit. There were no cases of overcorrection, migration, infection, or extraocular muscle entrapment. In complex orbital fractures, the technique of rigid internal orbital fixation appears to yield a stable and predictable result with the prevention of postoperative globe malposition. PMID- 1584575 TI - Optic nerve sheath meningioma. Definition of intraorbital, intracanalicular, and intracranial components with magnetic resonance imaging. AB - Magnetic resonance imaging with fat saturation after the administration of gadolinium-DTPA can detect and demarcate meningioma of the optic nerve sheath with a precision not attainable with any other current imaging technique. This article describes some of the clinical implications of this technique and illustrates the appearance of this tumor on magnetic resonance images. PMID- 1584576 TI - A functional scoring method for the field of binocular single vision. AB - The authors present a new method for plotting and quantitating the field of binocular single vision (BSV). They modified a Goldmann perimeter to project a fusion target in the form of a cross (+). Unlike previous methods that used a spot, which is a poor fusion target that cannot detect cyclotorsion, the authors' method permits a single tester to plot BSV fields in patients who have any combination of horizontal, vertical, and cyclotorsional diplopia. The BSV fields were plotted in 23 patients with acquired diplopia using both the fusion target and the spot. Scoring was performed using a new scoring template weighted to the functionally important areas around primary and reading positions. Nine patients (39%) had scores for the two targets that differed by more than 10%. The authors' method yields BSV scores that are reproducible and easy to perform and that can be used for preoperative and postoperative assessments, serial monitoring of changes over time, and disability evaluations. PMID- 1584577 TI - Extraocular muscle regeneration in primates. Local anesthetic-induced lesions. AB - Retrobulbar administration of several local anesthetics (0.75% bupivacaine, 2.0% mepivacaine or 2.0% lidocaine plus 1:100,000 epinephrine) in monkeys resulted in a low incidence of muscle fiber lesions in the extraocular muscles closest to the site of injection. Most lesions resulted in the degeneration and regeneration of muscle fibers on the surface of the muscles, but occasionally a massive internal lesion was seen. In contrast, large lesions were common in rectus muscles that received direct injections of local anesthetics in both monkeys and humans. The morphology and temporal sequence of muscle fiber degeneration and regeneration was similar to that seen in primate thumb muscles injured by anesthetic agents. PMID- 1584578 TI - Asymmetric inferior oblique overaction and its association with amblyopia in esotropia. AB - To evaluate the frequency of asymmetric inferior oblique overaction and its relationship to amblyopia, the authors reviewed the records of all patients who presented to Children's Hospital of Dallas with esotropia over a 2-year period. A total of 368 patients were identified and classified as infantile esotropia, acquired accommodative or partially accommodative esotropia, or acquired nonaccommodative esotropia. Two hundred forty-two patients (66%) had no amblyopia, of which 90% had symmetric inferior oblique activity. One hundred twenty-six patients (34%) had amblyopia; of these patients, 93 (74%) had symmetric inferior oblique action. Amblyopia was strongly associated with increased inferior oblique overaction in the amblyopic eye (P less than 0.001). This finding was consistent for all subgroups. The relative risk for having amblyopia as opposed to normal vision in an eye with increased inferior oblique activity relative to the contralateral eye was 5.6 to 8.6 depending on the eye. Amblyopia should be strongly suspected in patients with esotropia and asymmetric inferior oblique activity, specifically in the eye with more inferior oblique overaction. PMID- 1584579 TI - An electrolyte-based solution that increases corneal glycogen and conjunctival goblet-cell density in a rabbit model for keratoconjunctivitis sicca. AB - Thirty-two rabbits with monocular surgically induced keratoconjunctivitis sicca (KCS) underwent masked treatment for 12 weeks with 1 of 4 artificial tear solutions. Disease in each group of treated rabbits was compared with disease in untreated KCS controls. One of the solutions tested was a unique electrolyte based formulation shown previously to preserve normal goblet-cell density after extended exposure in normal rabbits. Only the electrolyte-based solution decreased elevated tear osmolarity and sodium after 9 weeks of treatment (P less than 0.05). At 20 weeks, mean corneal glycogen and conjunctival goblet-cell density in eyes treated with the electrolyte-based solution increased significantly relative to untreated KCS controls (P less than 0.01). With the other three solutions, mean glycogen levels and goblet-cell densities were either decreased relative to untreated KCS controls (P less than 0.05) or were unchanged. The electrolyte-based solution is the first treatment to increase corneal glycogen and conjunctival goblet cells in a rabbit model of KCS. PMID- 1584580 TI - Efficacy of laser punctal occlusion. AB - Dry eye is a common problem and in its more severe form may be treated with punctal occlusion. Photothermal coagulation of the puncta with the argon laser has recently been advocated to occlude the lacrimal puncta. Its long-term efficacy has not been investigated. The authors examined 22 puncta that had been occluded with the argon laser an average of 16 months before this study. Of the 22 puncta, 19 (86%) were patent. The results of our retrospective studies suggest that argon laser punctal occlusion is not an efficacious method for producing long-term punctal closure. The authors also used an animal model to investigate the effect on tissue of thermal cauterization and argon laser photothermal coagulation and found that thermal cauterization resulted in more widespread coagulative necrosis. PMID- 1584581 TI - Penetrating keratoplasty in patients with rheumatoid arthritis. AB - The authors reviewed in a retrospective manner 47 penetrating keratoplasties performed on 23 eyes of 21 patients with rheumatoid arthritis. The indications for the first penetrating keratoplasty were corneal melt in 19 eyes (83%), infectious keratitis in 2 eyes (9%), and corneal scarring after ulceration in 2 eyes (9%). Twelve of the 23 eyes required 24 repeat penetrating keratoplasties. Seventeen of the 23 eyes (74%) had clear grafts at the last follow-up visit, a median of 13.7 months after the last penetrating keratoplasty. The final best corrected visual acuity was greater than or equal to 20/60 in 4 eyes (17%), 20/70 to 20/100 in 1 eye (4%), 20/200 to 20/400 in 7 eyes (30%), counting fingers in 4 eyes (17%), hand motions in 2 eyes (9%), and light perception in 4 eyes (17%). One eye (4%) was enucleated. Anatomic success (absence of phthisis bulbi, enucleation, or conjunctival flap) was achieved in 20 eyes (87%). The survival probability for the 21 patients was only 48% 5 years after the first penetrating keratoplasty. The authors conclude that penetrating keratoplasty is often anatomically successful in patients with rheumatoid arthritis; however, the prognosis is poor for both vision and survival of the patient. PMID- 1584582 TI - Ultrastructural alterations in the endothelium in a patient with topical anesthetic abuse keratopathy. AB - A 40-year-old patient frequently self-administered topical oxybuprocaine drops for approximately 7 days after bilateral ultraviolet-light keratitis. Initially, he developed bilateral chronic epithelial defects with diffuse stromal infiltration and edema. After a protracted initial healing period, the patient underwent a penetrating keratoplasty in one eye because of significant corneal scarring. Pathologically, the corneal button revealed scarring and thinning of the central stroma. Results of scanning electron microscopy showed endothelial polymorphism, focal endothelial necrosis, and numerous filamentous processes emanating from abnormally enlarged intercellular gaps. Results of transmission electron microscopy showed markedly attenuated to absent apical cell attachments at the endothelial intercellular junction. Abuse of oxybuprocaine appears to produce irreversible damage to the apical cell attachments at the level of the corneal endothelial cells. PMID- 1584584 TI - Punctual occlusion for the dry eye. American Academy of Ophthalmology. PMID- 1584583 TI - Treatment of contact lens-related ocular surface disorders with autologous conjunctival transplantation. AB - The authors describe two cases of chronic ocular surface disorder caused by the use of soft contact lenses. These cases demonstrated persistent corneal epithelial abnormalities, indolent ulceration, superficial stromal scarring, peripheral vascularization, and decreased visual acuity (worse than 20/400). Both cases were refractory to medical management, including discontinuation of contact lenses and topical medications. Autologous conjunctival transplantation restored the ocular surface with the return of good visual acuity (better than 20/40). Tissue culture demonstrated a decreased replication rate in the limbal epithelial cells, which suggests that epithelial stem cell dysfunction may be responsible for this ocular surface disease. PMID- 1584585 TI - Use of the medicinal leech in the treatment of ear diseases. AB - Medicinal leeches (Hirudo medicinalis) and the native secretion of their salivary glands diluted with saline (5 times) were successfully used for the treatment of some ear diseases: tinnitus caused by inner-ear affections, acute external otitis and chronic otitis media. The effect of diluted leech saliva injected into the region of the mastoid process by microelectrophoresis was 25-30% lower than that of the medicinal leeches. PMID- 1584586 TI - Study of the effect of 350-Hz tone exposure on electrophysiological function of the inner ear of guinea pigs. AB - The effects of noise exposure were studied in fifty-nine 4- to 5-week-old albino Hartley guinea pigs with normal hearing (body weight 250-300 g). The following experiments and results were carried out: exposure to 350 Hz pure tones at 115 dB for 40 h and exposure to 350 Hz tones at 120 dB for 64 h. In order to investigate the effects of low-frequency tone exposures on the hearing of the guinea pigs, cochlear microphonics (CM), whole nerve action potentials (AP) and endocochlear potentials (EP) were measured. With a high-sound pressure, a decrease was observed in the CM maximum output voltage in the test frequencies of 2, 4 and 6 kHz while the CM threshold (pseudothreshold) of 6 kHz was elevated. Output voltage of the N1 potential of the AP using a 7-kHz tone burst decreased while the threshold of the N1 potential was elevated. An extension of latency and a decrease in the absolute value of the negative potential in EP were also observed. PMID- 1584587 TI - Pathogenesis of widened AP-SP complex in cases of cerebellopontine angle tumors. AB - Pathogenesis of widened AP-SP complexes often noted in electrocochleograms (ECochGs) in cases of cerebellopontine angle tumors remains unclear. As acoustic neuromas usually originate from the vestibular nerve, some changes in this nerve might be involved in producing the broadened waveform. Effects of lidocaine on the AP-SP complex were investigated in guinea pigs by injecting this compound into the root exit zone of the vestibular nerve, where the cochlear efferent fibers run together. The AP-SP complex in response to clicks and tone bursts was recorded at the bony wall of the scala vestibuli in the basal turn of the cochlea. Inactivation of the efferent cochlear fibers resulted in a marked widening of the waveform, independent of the interstimulus intervals (ISIs). This broad wave was composed of a DC shift which was quite similar to the envelope curve of the acoustic stimuli. Although the effect of activity of the efferent cochlear fibers on negative summating potential (SP) has not been reported in detail, the authors concluded that the broad waveform observed in ECochGs in cases with cerebellopontine angle tumors was caused by enhanced negative SP due to inactivation of efferent cochlear fibers. PMID- 1584588 TI - A modified method of electronystagmography for recording eye movement during the galvanic vestibular test. AB - This study demonstrates a new technique for recording galvanic nystagmus using conventional electrooculography: a first pair of electrodes is placed at the nasal and lateral orbital margin of the left eye. An additional pair of electrodes is placed near the left angle of the mouth. This latter pair of electrodes picks up voltage variations induced by heart beat but only a minimal part of voltage variations caused by eye movements during bipolar, binaural electric stimulation. Electronic subtraction of the voltage variations near the angle of the mouth from the voltage variations at the equilateral eye cancels the cardiac interference and allows a pure recording of horizontal eye movements. 35 of 40 subjects could be examined successfully. PMID- 1584589 TI - In vivo attachment of Streptococcus pneumoniae and Haemophilus influenzae to nasopharyngeal epithelium in children. AB - Attachment of Streptococcus pneumoniae and Haemophilus influenzae to epithelial cells on the posterior wall of the nasopharynx (NPH) was determined in 10 healthy children, culture-positive for either of these microorganisms. By using immunofluorescence technique and specific fluorescein-labelled antisera against these microorganisms, it was shown that in only 2 of the children studied were these pathogens firmly attached to the non-ciliated cells of the NPH. Attachment of S. pneumoniae and H. influenzae to the epithelial cells close to the nasopharyngeal opening of the Eustachian tube is of the utmost importance for the development of invasive disease, especially acute otitis media. Attachment of these pathogens to the epithelial cells covering the adenoid tissue may naturally be of significance for the induction of specific antibody body production against these microorganisms. PMID- 1584590 TI - Evidence of platelet-activating factor in nasal polyps. AB - Platelet-activating factor (PAF) was measured in human nasal polyps obtained from patients with chronic sinusitis. PAF was quantitated by platelet-aggregating activity and was found to be 7.8 +/- 1.8 pg/micrograms phosphorus of polyp phospholipid (mean +/- SE; n = 23). In the polyps, phosphatidylcholine constituted 30% of the total phospholipids, of which 8.5% was the ether-linked type. Incubations of replicates of the fresh polyps in Tyrode's solution in the presence of calcium ionophore A23187 and antihuman immunoglobulin E resulted in 295 and 65% increases in the amount of PAF, respectively. Thus, nasal polyps in humans with chronic sinusitis possess PAF and have the potential to produce PAF upon stimulation. The participation of PAF in nasal polyp formation is discussed. PMID- 1584591 TI - Supraglottic versus glottic laryngeal cancer: epidemiological and pathological aspects. AB - Between 1979 and 1988, 432 cases of previously untreated laryngeal cancers were histologically diagnosed at the Institute of Pathological Anatomy of the University of Trieste. Of these cases, 192 were supraglottic and 182 glottic cancers. The overall crude incidence was 31.06 0/0000 in males and 2.29 0/0000 in females, with a male/female ratio of 10.2:1 for supraglottic cancers vs. 20.4:1 for glottic cancers. Our incidence values for laryngeal cancer, and supraglottic lesions in particular, are similar to those recorded in France, Spain and other areas of Italy, i.e. in nations where wine production and consumption is very high. The 3-year adjusted survival rate was 45.7% for supraglottic and 83% for glottic cancer patients. Subjects with supraglottic cancer often had a poor prognosis because of the high frequency of cervical lymph node involvement, recurrences and visceral metastases; cancers of the aryepiglottic folds presented the worst clinical evolution. PMID- 1584592 TI - Effects of topical laryngeal lidocaine on sympathetic response to rigid panendoscopy under general anesthesia. AB - The sympathetic response to rigid bronchoscopy, laryngoscopy and esophagoscopy, performed under general anesthesia with isoflurane, was examined in patients who either received 5 ml of 2% lidocaine (n = 7) or 5 ml of saline (n = 7), sprayed on larynx and upper trachea under direct laryngoscopy, 2 min before the introduction of the rigid bronchoscope. Blood pressure, heart rate and plasma catecholamine and lidocaine levels were measured at specific time points of the study. Topical lidocaine led to a rapid and prolonged increase in plasma lidocaine levels. Patients treated with lidocaine showed a small but significant decrease in plasma epinephrine levels from baseline following endotracheal intubation and extubation, as compared to the saline control group. Blood pressure and heart rate response during rigid panendoscopy, isoflurane requirements and time interval from termination of panendoscopy to extubation were not different between the two groups. However, in contrast to the control group, patients who had received lidocaine had no significant rise in blood pressure and heart rate from baseline following the introduction of the rigid bronchoscope. The benefit of this moderate hemodynamic stabilizing effect of lidocaine has to be weighted against the risk of decreased protective airway reflexes due to topical laryngeal lidocaine during recovery from anesthesia. PMID- 1584593 TI - Ciprofloxacin and the inner ear--a morphological and round window membrane permeability study. AB - This study was conducted in order to evaluate ototoxic potential and passage through the round window membrane of ciprofloxacin, a newly developed antimicrobial drug with an antibacterial spectrum well suited for the treatment of suppurative otitis media. Ciprofloxacin was injected intraperitoneally in 40 guinea pigs in doses ranging from 25 to 150 mg/kg body weight for 14 consecutive days. Sixteen inner ears of chinchillas were exposed to ciprofloxacin at a concentration of 0.1 mg/ml applied directly to the intact round window membrane. Despite severe deterioration of the animals injected with the highest doses, no behavioral or definite morphological evidence of inner ear or vestibular damage could be seen. Ciprofloxacin concentrations in the perilymph were determined with high-performance liquid chromatography. Direct passage of ciprofloxacin, presumably via the round window membrane, was demonstrated. After 1 h and 15 min, an arithmetic mean concentration of 0.165 micrograms/ml (95% confidence interval +/- 0.053) could be demonstrated in the perilymph. It can be concluded that ciprofloxacin has no ototoxic effect when administered systemically. Furthermore, when locally applied into the middle ear, it has the capacity to pass into the inner ear. PMID- 1584594 TI - Heterotopic brain tissue of the soft palate. AB - Heterotopic brain tissue is an unusual substance which is very difficult to diagnose correctly preoperatively. We report on a 7-month-old male infant with heterotopic brain tissue of the soft palate, and describe the results of preoperative examinations including brain scintigraphy, angiography, brain computed tomography and magnetic resonance imaging (MRI). MRI was found useful to show that the tumor had no junction with the intracranial space. The patient was treated successfully without complication or recurrence after 1.5 years follow up. PMID- 1584595 TI - Tuberculous otomastoiditis. AB - A review of the 20th century English-language literature has produced a total of 320 cases of tuberculous otitis media or otomastoiditis, of which a surprising 93 cases have been reported in the 5-year period 1986-1990. Eighty-three percent of these have come from indigenous African populations. The international health and sociological implications of this development are disturbing. three personal cases seen during the past 8 years are presented, all of whom came from the indigenous Norwegian population. The epidemiology of these cases is therefore different, which can result in a diagnostic delay due to a low index of suspicion. The historically classical signs of this disease are frequently absent. PMID- 1584596 TI - [Treatment of patients with advanced ovarian cancer at the Gynecological Clinic of Pecs Medical University]. AB - Treatment protocols for advanced ovarian tumors (stages III-IV), applied at the author's institute, are presented. Giving a short survey the outcome with single agent cyclophosphamide therapy (C; n = 82), combinations without cisplatin (CMV, CAV; n = 83) or combination with cisplatin (CAP; n = 41) has been compared. A significant difference between C and CMV/CAV groups could be found only in regards with remission period (p = 0.0004 and 0.0001). By the use of CAP the result became better not only in the extent and the duration of remission but in the survival as well as compared to that of the other groups. The importance of the extent of residual tumor is emphasized. Because of serious side effects of particularly cisplatin based, three drug combinations the use of combinations consisting of two drugs only can be recommended in accordance with literary data. By the estimation of the usefulness of second look operation's findings the radiotherapy with its consolidationary effect and also the significance of a maintaining or a second line cytostatic treatment are pointed out. PMID- 1584597 TI - [Therapeutic possibilities in the management of Budd-CHiari syndrome (case reports and review of the literature)]. AB - The authors treated six female patients with Budd--Chiari syndrome. Having compared their own experience with the data of literature they concluded that the medical treatment of Budd--Chiari syndrome is usually without any success. Survival of the patients can only be expected by portosysthemic shunts or liver transplantation. PMID- 1584599 TI - [The value of transvaginal sonography combined with qualitative human chorionic gonadotropin determination in suspected extrauterine pregnancy]. AB - Effectiveness of ultrasonography, especially transvaginal sonography (TVS) combined with urinary human chorionic gonadotropin was examined in the assessment of 225 patients clinically suspected of having an ectopic pregnancy. HCG test was performed when pregnancy could not be found by transabdominal scanning. In case of negative result pregnancy was ruled out, in positive case TVS was used to localise pregnancy. In 60 patients correct diagnosis could be made with classical transabdominal scanning, TVS was required in 165 cases. In 144 patients a correct diagnosis was made during the first scan; 19 patients were rescanned for the final diagnosis. Ectopic pregnancy was successfully ruled out by transvaginal scanning in 115 patients by diagnosing an intrauterine pregnancy and 41 ectopic pregnancies were found, 33 by TVS and only 8 cases by transabdominal scanning. Two false negative identification occurred. The sensitivity, the specificity, the positive and negative predictive value of diagnosing ectopic pregnancy by TVS were 94.3%, 100%, 98.3% and 100%, respectively. The number of unruptured tubal pregnancies in this series was 64.5%. These results show that transvaginal ultrasonography is a sensitive method for diagnosing or excluding ectopic pregnancy. PMID- 1584598 TI - [Effect of estrogen on the blast transformation of lymphocytes and interleukin-2 production in lupus erythematosus]. AB - The mitogenic response of peripheral lymphocytes was investigated in 12 patients with systemic lupus erythematosus and in healthy female volunteers who were on 11 and without 9 contraceptive pills. The effect of estrogen (ethinyl-estradiol 10( 5)-10(-6)-10(-7)M) was studied on Phytohaemagglutinin and Pokeweed mitogen induced blastogenic transformation and interleukin-2 production of peripheral lymphocytes in vitro. We observed a significantly depressed Phytohaemagglutinin induced lymphoblastic transformation both in patients and women taking oral contraceptive in presence of 10(-5)M estrogen as compared to normal controls. However there was no significant alteration neither in the response of lymphocyte nor in the production of interleukin-2 using of Pokeweed mitogen. The stimulataneous inhibition of the interleukin-2 production proved to be moderate. Marked significant correlation (r greater than = 0.8) vas detected between lymphoblastic transformation and interleukin-2 production in healthy females. Correlation coefficient measured in females taking oral contraceptive (r less than = 0.64) and patients with systemic lupus erythematosus (r less than = 0.34) suggest that in these groups the inhibition of lymphoblastic transformation is due to the inhibition effect of estrogen on the interleukin-2 production. PMID- 1584600 TI - [Bilateral neonatal adrenal hemorrhage associated with hypoadrenalism]. AB - A newborn is described, who was born in term with 3250 g weight, after intrauterine hypoxia. She was born with vacuum extraction, and suffered from birth trauma and intrauterine infection. At age of one day manifested an eclampsia, which was hardly diminishable. The serum Na level was 118 mmol/l. Bilateral adrenal apoplexy was visible with ultrasound. The newborn was treated with infusion of sodium chloride and glucose, with antibiotic and glucocorticoid hormone. Her condition improved rapidly. Her serum cortisol level at 8 and 15 day after stopping of 12 days prednisolon therapy was below 2.5 micrograms/dl, marking hypadrenia. At age 3 months the function of adrenals was normal: the serum cortisol level was 11.4 micrograms/dl, and after ACTH stimulation it run up to 44.5 micrograms/dl. By screening of 1491 newborns, 13 adrenal apoplexy was found. The other 12 were one-sided and symptomless. PMID- 1584601 TI - [The shunt--lifeline of the dialysis patient]. PMID- 1584602 TI - [The dialysis nurse]. PMID- 1584604 TI - [The afflictions of Mr. H]. PMID- 1584603 TI - [Nursing today]. PMID- 1584605 TI - [Dialysis--in spite of it say yes to life]. PMID- 1584606 TI - Relations between dark accommodation and psychosomatic symptoms. PMID- 1584607 TI - A simple equation for relating AC/A ratio to accommodative controller gain. PMID- 1584608 TI - Determination of the nodal point position in the pseudophakic eye. PMID- 1584609 TI - Estimating the reliability of clinical tests. PMID- 1584610 TI - Psychophysical measurement of the size and shape of the human foveal avascular zone. AB - We have examined two psychophysical procedures for assessing the size and shape of the human foveal avascular zone (FAZ). Both procedures used a Maxwellian view system with a rotating beam to create a high contrast entoptic view of the retinal vasculature. Most subjects readily report a clear avascular zone surrounding their fixation point. The size of this FAZ was measured by (a) reducing the circular Maxwellian view field stop until it appeared to coincide with the edge of the FAZ, and (b) by tracing the boundary of the FAZ with a point source. Consistent with earlier angiographic and anatomical studies, the first method (N = 34 eyes) showed a mean FAZ diameter of 0.736 mm (area 0.42 mm2). FAZ diameter ranged from 0.46 to 1.13 mm (area 0.166-1.00 mm2) and the FAZ from the right and left eyes of each individual subject were very similar (r2 = 0.863). The tracing technique (n = 24 eyes) showed that FAZ's were generally not spherical but well fit by ellipses with, on average, a major axis 17% longer than the minor axis. The maximum diameters of the FAZ tracings were very similar and significantly correlated with the circle diameters matched to the FAZ in experiment 1. PMID- 1584611 TI - Tolerance to spherical aberration induced by rigid contact lenses. AB - We have investigated the effects of spherical aberration (SA) on visual performance by fitting subjects with rigid lenses of varying front surface asphericity. Three pairs of lenses were worn by each subject with front surface asphericities of Q = 0 (conventional spherical surface), Q = -0.26 (similar to the average corneal asphericity) and Q = -0.51. The calculated average change in spherical aberration induced by each pair of contact lenses in photopic conditions was +0.02 D (Q = 0), -0.49 D (Q = -0.26) and -0.94 D (Q = -0.51). In mesopic conditions these same lenses induced an average change in spherical aberration of +0.01 D (Q = 0), -1.18 D (Q = -0.26) and -2.16 D (Q = -0.51). In this double-blind study, 12 adapted, low to moderate myopic rigid lens wearers wore each pair of lenses for one week and noted visual performance. With each pair of lenses we also measured the subject's visual acuity with high and low contrast logMAR charts. All measurements were conducted using the right eye at distance in photopic and mesopic conditions. When forced to select the lenses they would accept as compensation for participation in the study, most subjects (9 out of 12) chose the Q = 0 lenses, 3 subjects those the Q = -0.26 lenses and none of the subjects chose the Q = -0.51 lenses. Visual performance measures showed little difference between the Q = 0 and Q = -0.26 lenses. However, the Q = -0.51 lenses significantly reduced visual acuity in mesopic conditions with the low contrast acuity chart. PMID- 1584612 TI - Variations in hyperacuity performance with age. AB - The term hyperacuity has been applied to a group of stimuli which produce spatial thresholds smaller than those expected given the relatively large receptor spacing and the retinal image quality of the human eye. It is not yet firmly established whether hyperacuity performance declines with increasing age in the same way as most other measures of visual ability. This is perhaps due to the use of varying task configurations and criterion-dependent psychophysical techniques. The present study examines age-related performance in three different hyperacuity tasks using a criterion independent forced-choice method. Both displacement and bisection thresholds were found to increase with age, but there was no significant change in vernier acuity. This indicates that age has a differential effect on thresholds for various hyperacuities depending upon the task requirements. No significant age-related trend was observed in hyperacuity bias, which represents the difference between subjective and true physical alignment. PMID- 1584613 TI - How optometrists screen for glaucoma: a survey. AB - All optometrists registered and practising in Leicestershire were surveyed to find out what facilities they have for glaucoma screening, how patients are selected for screening, what tests are performed, and the criteria used for referring patients to the hospital ophthalmic service. All respondents examine the optic disc of all patients: 99% have tonometry available, but most use it selectively, on the basis of age, family history and disc appearance. Although 88% have field testing apparatus, this is usually not of a type likely to be effective in screening a general population: 38% have automated or semiautomated perimetry. The criterion level of IOP at which 80% of respondents would refer was 27 mm Hg in the absence of disc cupping, falling to 24 mm Hg if cupping was suspected. Over 80% would refer any patient with a field defect irrespective of IOP. PMID- 1584614 TI - The influence of stimulus luminance and contrast on hyperacuity thresholds for oscillatory movement. AB - Hyperacuity thresholds for oscillatory movement were determined under conditions of decreased contrast and decreased luminance. Responses were found to be resistant to contrast reduction down to 15%; below this level thresholds increased. The contrast response function is thus similar to that of the magnocellular channel of the visual system. Systematic reduction in luminance caused a corresponding rise in thresholds. It is suggested that this effect is due to undersampling of the retinal image as a result of a lowered quantal absorption and an increase in critical duration of temporal integration at lower levels of luminance. PMID- 1584615 TI - The use of colour difference vectors in diagnosing congenital colour vision deficiencies with the Farnsworth-Munsell 100-hue test. AB - Colour difference vector analysis provides useful and meaningful information in scoring the Farnsworth-Munsell (FM) 100-hue test. However, the FM 100-hue test is limited in its ability to diagnose type and severity of congenital colour vision defect. Type classification for all subjects is incorrect in 21% of cases, and for deuteranomals the misclassification rate is 38%. Visual inspection of the plots yields a similar misclassification rate and classification of plots with few errors (under 180) is generally less reliable. The FM 100-hue test has a limited ability to separate dichromats from anomalous trichromats. A test protocol based on joint D15 and FM 100-hue tests should pass 36% of anomalous trichromats and 26% of all colour defectives yet fail all dichromatic observers. We conclude that administering the FM 100-hue test is of less value than a combination of D15 panels (Standard D15 and L'Anthony's desaturated D15) in the clinical diagnosis of congenital colour defective observers. Our results for the FM 100-hue panel are similar to those reported previously by other investigators. PMID- 1584616 TI - Regional variations in binocular summation across the visual field. AB - Binocular summation for a contrast detection task was measured as a function of eccentricity and target size along the horizontal and vertical meridians for ten young normal subjects. Binocular summation at the fovea was of the order of 1.4 for all target sizes, although there was some intersubject variation. Binocular summation was highest along the vertical meridian. With increasing eccentricity from the fovea, binocular summation for target size I (0.108 degrees projected diameter) decreased, remained relatively constant for target size III (0.431 degrees projected diameter) and increased with increasing eccentricity from the fovea for target size V (1.724 degrees projected diameter). For target sizes I and III, binocular summation was present only when interocular differences in sensitivity were under 5 dB, for target size V this relationship did not hold. Influences such as stimulation of corresponding retinal points and cortical representation are considered. PMID- 1584617 TI - Focimeter measurement of the astigmatism arising from oblique central refraction. AB - In this article, a method for measuring the astigmatism produced by an oblique central refraction is proposed. Measurements were taken using two different values of the pantoscopic angle that can be produced by lenses mounted in frames. We show that in specific cases, and as a function of the angle and power of the lens, the resulting astigmatism can surpass the tolerance level of the eye. PMID- 1584618 TI - Calculation and least-squares estimation of surface curvature and dioptric power from meridional measurements. AB - The calculation or estimation of dioptric power or surface curvature from meridional measurements is an important problem with applications in a number of areas. By phrasing the problem in terms of matrices and applying new results in the mathematics of matrices one is able to reformulate the problem into a standard form that is well known in mathematics and statistics. As a result the solution can be written down directly. The method copes with any number of measurements along any number of meridians, including repeated measurements along the same meridian, and is more general than methods previously proposed. It gives least-squares and best estimates of the true surface curvature or dioptric power. Being phrased in standard statistical terms the method lends itself readily to extension to related types of problems such as least-squares estimation under certain types of constraints. Matrix methods employed in this paper are likely to find wider application in optometry and the vision sciences. PMID- 1584619 TI - Constrained least-squares estimation of surface curvature and dioptric power from meridional measurements. AB - A dioptric power or surface curvature may be presumed or known to be of some particular type, for example spherical, or astigmatic and with a particular nearest equivalent sphere. Such knowledge or presumption represents a constraint on the power or curvature. This paper shows how meridional measurements can be used to obtain least-squares estimates of surface curvature or dioptric power under the constraint. PMID- 1584620 TI - Inter-observer variability in a computer-assisted optic nerve head assessment system. AB - A computer-assisted optic nerve head analysis system was used to measure parameters of the optic nerve head from one eye from each of 15 subjects. The subjects comprised three groups of five, being glaucomatous, ocular hypertensive, and normal. The 15 images produced were analysed in a randomized masked fashion by ten observers of varying levels of experience to test the inter-observer variability of the measurements. An analysis of variance demonstrated significant differences in the measurements made by the different observers. Fisher's F-test showed that all the parameters assessing the pallor area of the optic nerve head had significantly lower inter-image variance (reported previously) compared with inter-observer variance (at the 5% level). Variability in taking measurements of the pallor area of the optic nerve head is mainly due to observer variations rather than the image variations. PMID- 1584621 TI - Scanning laser measure of optical quality of the cultured crystalline lens. AB - An apparatus has been designed to automate the laser measuring technique and make it possible to monitor lens refractive function (spherical aberration) as well as change in lens transmittance during lens culture. A scanning laser beam (helium neon) is used so that a number of beams pass through different spots on the lens to determine lens spherical aberration compared over time. Each refracted beam, received by two video cameras (X and Y directions), is digitized. The system first locates the optical centre of the lens by determining the beam position providing the least deflection for both the X and Y directions. The beam is then moved in predetermined steps on either side of the centre, and focal lengths are determined relative to the optic axis for each position. A measure of beam scatter is noted from post-refraction pixel excitation for each beam position. Improvements to the scanning laser system have led to greater accuracy and speed as well as to improved culture cells. Accuracy was increased by using high resolution (1 micron) stepping motors to move the scanning helium-neon laser. A new alignment process involving the superposition of the incident beam reflected on itself ensures that the incident beam is perpendicular to the lens equatorial axis. Scanning speed has been improved through a variety of hardware and software changes. Scanning time for a lens, including locating the optical centre and measuring focal length for 20 lens positions along the X and Y directions, takes about 60 seconds. Long-term studies on the degradation of lens optical performance frequency yield diffuse beams of very low intensity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584622 TI - Dynamic retinoscopy and accommodation. AB - The added positive lens power required for low and high neutrals at a distance of 1/3 m is determined as a function of age for a sample of 221 clinically normal subjects, aged between 10 and 80 years. These dynamic retinoscopy results are compared with corresponding laser optometer measurements of the levels of accommodation under each condition. Dark focus (tonic accommodation) measurements are carried out on a further sample of 58 subjects. Although the mean results of dynamic retinoscopy agree with those found by earlier authors, on the basis of our sample it is concluded that the considerable scatter in neutral values found in normal subjects at any age limits the usefulness of the technique as an indication of abnormality in near responses. Much of this scatter in pre presbyopic subjects appears to be related to individual variation in the level of tonic accommodation, although near phoria may also play some role. PMID- 1584623 TI - Contrasts in vision 1991. Cambridge, 5-6 September 1991. PMID- 1584624 TI - Controversies regarding the pathology of thymomas. PMID- 1584625 TI - Sex steroid receptors in gynecologic neoplasms. PMID- 1584626 TI - Cholesterol atheromatous embolism. The great masquerader revisited. PMID- 1584627 TI - Pathology of ciliated metaplasia of the human stomach. PMID- 1584628 TI - The histiocytoid hemangiomas and other controversies. AB - We have reviewed the clinicopathologic features of Kimura's disease, angiolymphoid hyperplasia with eosinophilia, epithelioid hemangioma of the testis, epithelioid hemangioendothelioma, spindle cell hemangioendothelioma, malignant endovascular papillary angioendothelioma of childhood (Dabska's tumor), epithelioid angiosarcoma, angioblastoma of Nakagawa, bacillary angiomatosis, verruga peruana, and other inflammatory angiomatoses. On the basis of our experience and reading of the literature, we conclude that angiolymphoid hyperplasia with eosinophilia, histiocytoid hemangioma of the testis, epithelioid hemangioendothelioma, and probably spindle cell hemangioendothelioma, constitute a group of related conditions best called the histiocytoid hemangiomas. Kimura's disease, Dabska's angioendothelioma, epithelioid angiosarcoma, and the inflammatory angiomatoses are not histiocytoid hemangiomas. Angioblastoma of Nakagawa is not related to lobular capillary hemangioma (pyogenic granuloma). PMID- 1584629 TI - Classification of metaplastic carcinomas of the breast. PMID- 1584630 TI - Managing angry feelings: teaching troubled children to cope. AB - Children who have a history of physical and emotional abuse present special problems to nurses who attempt to teach them more effective ways of dealing with anger. Since the adults in abused children's lives have not modeled constructive conflict resolution, the social and cultural learning about aggression in such children frequently has been inadequate. The author asserts that because nurses are in close contact with the children and can observe patterns of behavior during their regular daily activities, hospitalization may prove the ideal situation to teach such children appropriate social and assertiveness skills. PMID- 1584631 TI - Suicidal and nonsuicidal coping methods of adolescents. AB - The authors investigated the coping methods used by adolescents hospitalized for suicidal behaviors and adolescents hospitalized for nonsuicidal behaviors. The authors' purpose was to determine if a significant difference between the two groups existed. The findings suggested that adolescents with suicidal thoughts and behaviors use affective-oriented coping methods to a more significant degree than they use problem-solving strategies. The nonsuicidal group was found to use both affective and problem-oriented coping methods. PMID- 1584632 TI - Homosexual preoccupation in a gero-psychiatric client: a case for psychoanalytically oriented therapy. AB - The author embraces the theoretical position that the failure of a girl to establish female identification is preceded by failure to individuate, which causes a regression to an earlier, symbiotic stage. She believes that this is particularly relevant in relation to the aging homosexual female, given that significant loss and separation occur in later life. The capacity to cope with separation and loss can only develop if the individual is capable of self-object differentiation. The case history of a 70-year-old female homosexual is presented to support the author's conclusion that psychoanalytically oriented therapy is the treatment of choice for the aging homosexual female. PMID- 1584633 TI - The afternoon of life: Jung's view of the tasks of the second half of life. AB - The second half of life is marked for some by depression and an absence of meaning. Carl Jung believed that middle and old age, like youth, have specific developmental tasks. While the developmental tasks for youth involve turning outward and engaging life, the goal for the mature individual is to consolidate an integrated personality by integrating the conscious and the unconscious parts of self. The application of Jungian principles with mature depressed clients in the clinical care setting is discussed. PMID- 1584634 TI - Helping the elderly person resolve integrity versus despair. AB - The author describes ways in which the nurse can help the elderly person master the developmental stage of integrity versus despair through the use of a life review process. The author asserts that using the life-review process highlights the elderly person's assets rather than deficits. PMID- 1584635 TI - What role philosophy in psychotherapy? PMID- 1584636 TI - Treating the elderly mentally ill at home. AB - Psychiatric home health nursing provides an emerging arena for treating elderly clients diagnosed with major mental disorders. Client autonomy is maintained, and treatment can be tailored to individual need. The authors describe the concept of home care for the elderly mentally ill and issues related to funding and providing services. To illustrate the broad scope of available nursing treatment for the elderly, three case studies of clients with diagnoses of anxiety/depression, schizophrenia, and bipolar disorder are discussed. PMID- 1584637 TI - My brother's keeper: simultaneous hospitalization of siblings. AB - Milieu therapists are confronted with a dilemma when more than one child in the same family requires hospitalization. Conventional wisdom discourages simultaneous hospitalization of siblings on the same unit. The sibling bond, however, is an important aspect of development and can be used therapeutically. This paper examines issues and opportunities presented to milieu therapists by the simultaneous hospitalization of siblings, and makes recommendations for maximizing therapeutic use of the sibling bond. PMID- 1584638 TI - Lower limb amputee survival. AB - A total of 1710 primary amputees have been studied over a 25 year period and their survival time has been calculated. These were all consecutive primary lower limb amputees admitted to the Dundee Limb Fitting Centre during the period 1965 1989. Overall, the median survival was 4 yr 9 mth for the below-knee amputee (1019 patients) and 4 yr 3 mth for the above-knee amputee (586 patients). The vascular related amputees had an overall median survival of 4 yr. In the two decades 1970-1979 and 1980-1989 there were significant differences between the survival time of the below-knee and above-knee amputee. The survival of the amputee has increased during the two decades from 3 yr 6 mth to 6 yr 6 mth (p greater than 0.001). For the first decade male above-knee and male below-knee amputee median survival was 3 yr 1 mth and 3 yr 11 mth respectively and for the second the survival was 5 yr 9 mth and 6 yr 11 mth for these levels of amputation. For 1970-1979 no significant differences were found between male and female peripheral vascular disease (PVD) and diabetes mellitus related amputee survival. For 1980-1989 significant differences were found between PVD related male above-knee amputees (3 yr 10 mth) and male below-knee amputees (6 yr 7 mth) (p greater than 0.01). Similar results were found for the female patients. Operative mortality was found to be 5% over the period 1975-1989 which compared favorably with previous studies. PMID- 1584639 TI - Running gait impulse asymmetries in below-knee amputees. AB - In running, large gait asymmetry is expected due to the inability of the foot prosthesis to comply with the kinematic demands and produce a powerful plantarflexion moment. In this work, interlimb asymmetry in below-knee (BK) amputee running gait was assessed for one rigid and three flexible keel prostheses, using vertical and anteroposterior ground reaction forces and respective impulses. Nine BK amputees and 6 controls participated in this study. The running speed was monitored by two light sensitive detectors while the ground reaction forces were measured with a Kistler force plate. Between the prosthetic side and the sound limb the impulse indicator showed greater asymmetry than the force. Interlimb asymmetry was very much present in all types of prosthesis tested but is less pronounced in the flexible keel prostheses. In the latter, the asymmetry may be associated with the force-time history modulation rather than its magnitude alone. Generally, the impulses better describe interlimb asymmetry and the forces allow a greater discrimination between prosthetic foot types. PMID- 1584640 TI - The social and economic outcome after upper limb amputation. AB - This paper reports a study of 66 upper limb amputees in County Funen, Denmark who were visited in their homes by the author. The purpose of this study was to evaluate for the same period of time the social and economic outcome for a population of upper limb amputees compared with the normal population. The number of amputees investigated corresponds to the annual number of persons becoming upper limb amputees in Denmark. The aetiology of registered amputees also corresponds to the Danish Amputation Register. The amputees had become "better placed" in the social system after amputation independent of prosthetic use. The mean age of the amputees corresponded with the age where people reach their best social grouping. Their social migration quotient was higher than the background population and reflected the amputees better income and housing conditions. The reasons for these surprising results must be the high grade social system in a sophisticated industrial county. None of the amputees were required to pay for rehabilitation or prosthetic supply. A lower divorce rate for the amputees was explained by a symbiosis between the amputees and their partners to protect their future existence. Only 14% lived alone. Those who had their sexual debut after amputation were 3 years later in sexual experience than the rest of the amputees because of difficulties during the maturing process. PMID- 1584641 TI - Functional benefit of an adaptive myoelectric prosthetic hand compared to a conventional myoelectric hand. AB - Eight patients with a traumatic unilateral upper limb amputation, who used conventional myoelectric prostheses, were also fitted with a commercially available myoelectric prosthetic hand with an adaptive grip, in order to compare the functional benefit of the two types of prostheses. Comparisons were made regarding width of grip, force of grip, scores in a standardised grip function test and prosthesis preference. The conventional prosthesis showed significantly better results regarding these parameters. The adaptive hand does not appear to be fully developed for practical use in prosthetic rehabilitation. PMID- 1584642 TI - Prosthetics and orthotics: a survey of centres in the Kingdom of Saudi Arabia. AB - This paper reports the results of a survey carried out to evaluate existing prosthetic and orthotic facilities and programmes of education, training, and research and development in the Kingdom of Saudi Arabia. One hundred and twenty hospitals and medical rehabilitation centres were each circularised with a questionnaire requesting information that mainly concerned (i) types of prostheses/orthoses, (ii) area of facility, (iii) personnel number and qualifications, and (iv) problems encountered and suggested solutions. The completed questionnaires revealed that in the final analysis of data there were only ten prosthetic/orthotic facilities. The survey provided useful data on the personnel, equipment, and facilities available in each hospital or medical rehabilitation centre, together with details of the services to prospective referring clinicians. Two centres were found to provide high quality services by qualified personnel. There were no formal prosthetic/orthotic training programmes and there was only one prosthetic/orthotic research and development centre. The respondents generally felt that there were three major problems: (i) lack of qualified personnel, (ii) lack of materials and components, and (iii) lack of continuing education and training programmes. It is hoped that presentation of these results will provide facts for both health-care providers and educators which may be used as a basis for development in this important area of healthcare. PMID- 1584643 TI - The ORLAU VCG (variable centre of gravity) swivel walker for muscular dystrophy patients. AB - Swivel walkers are being increasingly used for muscular dystrophy patients in order to prolong the period of their ambulation. Existing designs did not address the special problems of accommodating such patients comfortably and providing the easier and more assured ambulation which their weakened condition requires. The ORLAU VCG (variable centre of gravity) swivel walker has been developed so that the walking mechanics can be adjusted independently of patient posture. Additional patient support features permit the patient to be secured in their chosen position of comfort prior to setting the ambulation mechanics. Patients using the device, which is now approved for supply by the Department of Health in England and Wales, have improved their walking performance and extended their period of walking. PMID- 1584644 TI - Primary orthotic treatment of ruptured ankle ligaments: a recommended procedure. AB - The results of a study after 1 and 2 years of a prospective randomised trial of operative versus conservative treatment of ankle ligament rupture, demonstrate that purely functional orthotic therapy is the method of choice. This relates both to patient need and economical considerations. The trial demonstrated that without an operation it was possible to achieve a high degree of mechanical stability, a reduction of work disability time down to 3 weeks and full sports capability within 3 months. Consequently, and as a result of the trial, the only remaining surgical indications would seem to be dislocations of the foot and ankle, ankle ligament rupture with additional intra-articular pathology, and second-stage injuries or re-ruptures. The joint-stabilising function of the prototype splint developed in this study was improved on the basis of experimental investigations, using a Y-shaped leather band (designated CALIGAMED), which is available in 6 sizes for right and left ankle. PMID- 1584645 TI - Application of a shape memory alloy to hand splinting. AB - This paper describes new passive splints which have been developed using a shape memory alloy. The peculiar feature of the splints is that the way in which they change shape in use conforms to the stretching motion which it would be desirable to apply in certain conditions of deformity. The alloy consists of 55.66% by weight Nickel and 44.34% Titanium. The heat treatment of the alloy for memorising shape was implemented at 500 degrees C for one hour. This alloy was easily bent when cool, but the original shape was recovered on heating. It was used as the supporting structure of the reverse knuckle bender splint and the cock-up splint. The new splints could be easily attached to the deformed limb after cooling. The splints avoided the development of spasticity, because they gradually recovered their original shapes and corrected the deformities when the heat of the room or body heat warmed the splints. Since the shape memory alloy has the dual function of thermal sensor and kinetic power source it was a simple device. The splint was, as a result, small and smart. It was apparent from clinical use that the splint was easy to wear and could be worn with comfort for an extended period. The design of the splints and the fabrication process are described and their application is indicated. PMID- 1584646 TI - A remarkable transport device for a fibrodysplasia ossificans progressiva patient. AB - This article contains a case report and a general description of a patient with fibrodysplasia ossificans progressiva. This is followed by a description of the design of a standing and transport device. PMID- 1584647 TI - Quality imperatives in long-term care. PMID- 1584648 TI - A strategy for quality assurance in long-term care. PMID- 1584649 TI - OBRA as a measure of quality. PMID- 1584650 TI - The future of quality in long-term care. PMID- 1584651 TI - Breaking out of the Skinner Box. PMID- 1584652 TI - Assuring quality in long-term care: the private sector approach. PMID- 1584653 TI - Faculty-student publication. PMID- 1584654 TI - Development of the Applied Liberal Education Competences Scale. AB - This article describes the development and initial psychometric testing of the Applied Liberal Education Competences Scale, an instrument designed to measure professional nurses' self-reported use of selected applied liberal education competences in professional practice. The ALECS was created using a conceptual model proposed by Stark and Lowther (1988a) and content validity was assessed using an expert panel. Construct validity and internal consistency reliability of the ALECS were examined and the instrument refined. This 67-item instrument consists of six subscales: leadership, contextual practice, professional development, analytic practice, reflective practice, and aesthetic practice. Since the instrument taps dimensions other than technical skills and specific role functions, it will enable educators and service personnel to better understand how nurses think and perform. PMID- 1584655 TI - Nursing care requirements and resource consumption in home health care. AB - Nursing care requirements provide the rationale for nursing practice. Two representations of nursing care requirements are nursing intensity and nursing diagnoses. In the present study, these two indicators each significantly explained variation in nursing resource consumption in home health care. Further study is needed to refine a measure of nursing intensity that has construct validity and a base in nursing theory. In addition, techniques are needed for grouping and weighting the various nursing diagnoses to reflect their contribution in explaining the amount of care provided to patients. PMID- 1584656 TI - Systemic responses to different enteral feeding schedules in rats. AB - The purpose of this study was to describe selected temporal systemic responses to different enteral feeding schedules using an animal model, as one prerequisite for determining optimal delivery times for human enteral feedings. The effect of feeding schedules and time of day were examined relative to body weight and plasma glucose, insulin, glucagon, and corticosterone levels. Adult male Sprague Dawley rats (N = 80) were used in a 4 x 4 randomized block design. Rats started the feeding schedules on Day 11 post-gastrostomy tube placement. The following feeding schedules, often used by humans, were tested: 24-hour enteral; 24-hour oral; 12-hour (rest time) enteral; and 12-hour (rest time) oral. Plasma was collected on Day 20. Despite very different feeding schedules, there were no statistical differences in weight gain, or plasma glucose and glucagon levels. Levels of insulin and corticosterone were significantly influenced by time of day and/or feeding group. Temporal pattern disruption was greatest in the rest-time fed enteral group. Both route and timing of enteral delivery modified metabolic hormone patterns. PMID- 1584657 TI - Alternate explanations of loneliness in adolescents: a replication and extension study. AB - Alternate explanations of loneliness proposed by Weiss (1973)--the situational theory and the characterological theory--were tested in samples of early (N = 113), middle (N = 106), and late (N = 106) adolescents. In addition to completing the Revised UCLA Loneliness Scale, participants completed instruments linked to either the situational or characterological explanation of loneliness. Data were analyzed using hierarchical analysis of sets. For early adolescents, the results indicated that the characterological set of variables explained somewhat more variance in loneliness than did the situational set of variables. These findings did not replicate those of the original study (Mahon & Yarcheski, 1988). For middle and late adolescents, the results indicated that the situational set of variables explained more variance in loneliness than did the characterological set. PMID- 1584658 TI - Facilitating inactive awake states in preterm infants: a study of three interventions. AB - Inactive awake behavioral states have been associated with reduced heart rates and more successful feeding in preterm infants. The purpose of this study was to test the efficacy of three different interventions to facilitate these optimal feeding states. Twenty preterm infants (gestational ages 27-33 weeks, M = 31.6, SD = 1.7; birth weights 931-2,140 grams, M = 34, SD = 373) serving as their own controls were randomly administered nonnutritive sucking, nonnutritive sucking plus rocking, and stroking interventions; and a control condition. There were significantly more inactive awake states with the nonnutritive sucking and nonnutritive sucking plus rocking interventions than with the stroking intervention and the control conditions. The results suggest that there are interventions that can help preterm infants in the transition from gavage to oral feeding and potentially shorten their hospital stays. PMID- 1584660 TI - The lived experience of postpartum depression: a phenomenological study. AB - The purpose of this phenomenological study was to describe the essential structure of the lived experience of postpartum depression. Seven mothers who had suffered from postpartum depression were interviewed regarding their subjective experiences. Data were analyzed using Colaizzi's (1978) method of phenomenology. Forty-five significant statements were extracted and clustered into 11 themes. These results were integrated into the essential structure of postpartum depression. Postpartum depression was a living nightmare filled with uncontrollable anxiety attacks, consuming guilt, and obsessive thinking. Mothers contemplated not only harming themselves but also their infants. The mothers were enveloped in loneliness and the quality of their lives was further compromised by a lack of emotions and all previous interests. Fear that their lives would never return to normal was all-encompassing. PMID- 1584659 TI - Vulnerability and temperament in very low birth weight school-aged children. AB - The purpose of this study was to investigate parental perception of vulnerability, parental subjective stress concerning children's premature birth, and child temperament in families of very low birth weight (VLBW) and normal birth weight (NBW) children. The subjects were 39 VLBW children and 30 NBW 7-year old children and their caregivers. Data on child temperament and parental perception of vulnerability was provided by the 69 families. Families of the VLBW group rated their degree of current stress concerning their children's premature birth. There were no differences between the NBW and VLBW caregivers in their perceptions of their child's vulnerability status. Caregivers of VLBW children had significantly lower scores on degree of subjective stress specific to the premature birth than the value reported on the standardization population. Child temperament made a significant contribution to parental perception of child vulnerability status in both VLBW and NBW parents. PMID- 1584661 TI - Predicting AIDS patient care intentions among nursing students. AB - Predictors of intentions to care for AIDS patients were examined among 153 sophomore and senior nursing students. Multiple regression analysis revealed that students who had relatively less AIDS knowledge and who perceived greater occupational risk of HIV infection expressed stronger intentions to avoid caring for AIDS patients. However, avoidance intentions were not simply a function of concern about personal health and inadequate knowledge. Students who held more negative attitudes toward intravenous drug users also had stronger intentions to avoid caring for AIDS patients, even when the effects of AIDS knowledge and perceived occupational risk of HIV infection were controlled. AIDS content is incorporated in the nursing curriculum for these students beginning in the junior year. Multivariate analysis of variance performed to determine the effects of this content revealed a significant effect for year in school considering all the dependent variables simultaneously. Seniors had lower avoidance intentions, lower perceived occupational risk, and greater AIDS knowledge than did sophomores. PMID- 1584662 TI - Personal risking: lesbian self-disclosure of sexual orientation to professional health care providers. AB - Thirty-three lesbians ranging in age from 18-68 participated as respondents in this qualitative, theory-generating study. Data were obtained through a written demographic questionnaire and in-depth taped interviews. Findings revealed a two phase basic social process (BSP) identified as personal risking that is used by lesbians to secure their physical and/or psychological safety within the health care system. In the anticipatory phase, the risk of self-disclosure is calculated using both imaginative and cognitive strategies to determine a disclosure stance. In the interactional phase, scanning and monitoring enable the lesbian client to reevaluate the stance assumed. The data confirm that lesbians are uncomfortable in many health care situations and suggest provider responses to improve their comfort and the level of health care they receive. PMID- 1584663 TI - The clinical research center: important resource for the nurse investigator. PMID- 1584664 TI - Instrumentation in cross-cultural research. PMID- 1584665 TI - Re: 'Effectiveness of the auscultatory method in predicting feeding tube location'. PMID- 1584666 TI - Re: 'Informing the media'. PMID- 1584667 TI - Re: 'Making practice perfect'. PMID- 1584668 TI - Nurse Marjorie Heeley and the Mother's Club. PMID- 1584670 TI - Mission of mercy. PMID- 1584669 TI - M2: teamwork. Part (ii): Managing a team. PMID- 1584671 TI - Worrying policy. PMID- 1584672 TI - Testing period. PMID- 1584673 TI - Homeward bound. PMID- 1584674 TI - The hidden illness. PMID- 1584675 TI - Choosing painkillers. PMID- 1584676 TI - Freedom to speak out. PMID- 1584677 TI - Dreams of leaving. PMID- 1584678 TI - Looking at care. PMID- 1584679 TI - Layers of meaning. PMID- 1584680 TI - Rhesus incompatibility. PMID- 1584681 TI - Sixth sense. PMID- 1584682 TI - 'All i could do'. PMID- 1584683 TI - A long night. PMID- 1584684 TI - More than a letter needed on HIV risks. PMID- 1584685 TI - Making sense of obstructive sleep apnoea in children. PMID- 1584686 TI - Professional development. Distinguishing characteristics. PMID- 1584687 TI - Measuring violence in mental health patients. PMID- 1584688 TI - Looking for non-adherence. PMID- 1584689 TI - Healing physiology. PMID- 1584691 TI - Nursing interventions. PMID- 1584690 TI - Cleaning choices. PMID- 1584692 TI - Defining and validating nursing interventions. AB - A research team at the University of Iowa has been working for 5 years to develop a classification of nursing interventions. Conceptual work to clarify the nature of a nursing intervention was needed. An inductive approach was taken to group discrete nursing activities and attach a conceptual label. Fehring's methodology was adapted for soliciting input from nurse experts for the 134 labels described in this issue. These labels are a part of the standardized language in the Iowa classification. PMID- 1584693 TI - Interventions related to respiratory care. AB - Nursing interventions provide the link between nursing diagnosis and patient outcomes. The validation of nursing interventions is the starting point for a standardized nursing language. This study adapted a method for the validation process for nursing interventions and identified interventions that nursing experts believe are vital to the care of respiratory patients. The study served as the pilot for further surveys by the Iowa classification project. Based on the results of this study, the group made modifications in the survey process. Specifically, national samples of nurses were used, definitions were included in the surveys, and standard deviations were calculated for each activity. The subsequent articles in this issue demonstrate these changes. PMID- 1584694 TI - Interventions related to neurologic care. AB - Patient outcomes in the neuroscience patient population can be optimized by appropriate and timely selection of nursing actions and interventions. This study is contributing to the advancement of neuroscience nursing by identifying 13 intervention labels with more than 300 activities to be used in the planning and delivery of care of these patients. Implications for further research are multiple, including a need for clinical research regarding the appropriateness and effectiveness of the items as well as establishing the frequency with which these items occur in clinical practice. PMID- 1584695 TI - Interventions related to pain. AB - A two-round Delphi survey was completed by pain experts to achieve consensus on 10 selected pain interventions and associated activities characteristic of each intervention. Consistently high scores were obtained by the raters for each intervention and activity, with most activities perceived as critical to the intervention. Interventions with more specific activities were rated highest by the expert judges. Expert feedback indicates the complexity of establishing a list of activities for selected interventions when dealing with pain of various types, with different causes and for different patient populations. The expert raters clearly see assessment and evaluation activities as part of the intervention strategies for each intervention. Further research is needed to validate the interventions and activities with nurse experts from varying clinical specialty areas in the practice setting. PMID- 1584696 TI - Interventions related to patient safety. AB - Patient safety is a growing priority in today's increasingly complex, highly technologic, and business-oriented health care system. This increasing emphasis is being fueled by issues such as cost containment, risk management, quality assurance, health care consumer activism, and legal accountability for practice. In such an environment, it is important that nursing be able to quantify and communicate what it does to promote and maintain patient safety. A standardized language of patient safety interventions provides nursing with the tool to do this. It provides a common language to use when dealing with patient safety issues in the practice, education, research, and administrative arenas. It also allows nurses to package and market the "product" of nursing care to health care consumers, other health care professionals, hospital administrators, and politicians, all of whom share an interest in ensuring that patient safety is maintained and promoted in the most comprehensive yet cost-efficient manner possible. PMID- 1584697 TI - Interventions related to patient teaching. AB - This study validated 13 nursing interventions related to patient teaching. Four of the labels address the process of patient teaching, whereas the other nine concern content specific to teaching efforts. With the help of 46 master's prepared nurses from across the country, critical (major) and supporting (minor) activities for each label were identified. This study is one of many steps toward the construction of a taxonomy of nursing interventions focused on direct care treatments that nurses perform on behalf of patients. The ultimate goal is to provide nurses with a standardized language that can be used to document their unique role in providing quality patient care and provide an appropriate avenue for reimbursement of nursing services. PMID- 1584698 TI - Interventions related to parent-infant attachment. AB - This study of nursing interventions that promote attachment is but one of the building blocks in creating a theoretically strong foundation for nursing practice. With the cooperative and coordinated efforts of nursing theorists, researchers, academicians, and seasoned practitioners, nursing will be able more clearly to define its domain of practice by identifying nursing interventions and the critical and supportive activities that comprise these interventions. With such systematically organized and tested knowledge, nursing practice will become firmly rooted in a knowledge base that will not only lead to improved patient care but enhance professional credibility and satisfaction. PMID- 1584699 TI - Interventions related to circulatory care. AB - The validation of 21 circulatory nursing interventions has helped to articulate one component of critical care nursing. Circulatory nurses intervene in actual or potential physiologic problems and have distinct treatments to offer. The validation of these circulatory interventions will help in the building of a standardized language for nursing. PMID- 1584700 TI - Interventions related to compliance. AB - Compliance by clients with prescribed health care regimens has become an area of intense interest for health care providers. With statistics pointing to the fact that patient compliance can range anywhere from 10% to 94%, there is a definite need for strategies that are available to health care providers, in particular nurses, to assist clients in adhering to their health care regimens. Although much research has been done to measure compliance and identify determinants, little has been done in the area of developing specific strategies and interventions to assist clients with their lifestyle changes. Nurses, using empirically validated nursing interventions to treat identified problems or nursing diagnoses, are in the unique position of being able to impact and enhance the clients' ability to adhere to their prescribed regimens. In this study a total of 225 nursing activities were identified to operationalize the five selected nursing interventions and were rated by 32 master's-prepared nurses certified in the area of diabetes education and psychiatric/mental health. Four activities received weighted ratios of less than 0.50 and were thus discarded. One hundred nine (48%) received ratios of less than 0.80 and are considered minor supporting activities, and 112 (50%) were weighted as greater than or equal to 0.80 and are thus considered major supporting activities. The ICV scores for the five nursing interventions ranged from 0.76 to 0.81. PMID- 1584701 TI - Interventions related to surveillance. AB - This study defined 10 nursing interventions that focus on purposeful acquisition, interpretation, and synthesis of patient data for clinical decision making. Critical and supporting activities used to carry out these interventions were delineated. Organizing and naming of monitoring activities are essential first steps to legitimizing, documenting, and investigating this area of professional nursing practice. PMID- 1584702 TI - Interventions related to family. AB - This group of 9 interventions related to families is a beginning in the work that lies ahead as nurses specify, validate, and test their interventions for the health and well-being of families and family members. It is the hope of the investigators that the reported findings and the discussion in this article will stimulate thought, action, and research as the practice and the science of nursing moves toward a standardized language for nursing diagnoses, interventions and outcomes. PMID- 1584703 TI - Interventions related to activity and movement. AB - Ten nursing interventions related to human activity phenomena with definitions and a combined total of 246 defining activities were developed from literature reviews and concept synthesis. A two-round Delphi survey of highly experienced master's-prepared rehabilitation nurses confirmed the content validity of the interventions. Round 1 responses resulted in major revisions of several interventions that were questioned and viewed as being outside the domain of nursing practice. Respondents also indicated that some of the activities listed were "idealistic" and that factors such as limited staffing, institutional policy, and physical characteristics of the unit would limit implementation. None of the activities rated in round 2 were deleted for means less than 0.50. The interventions with the highest ICV scores were Swallowing Therapy (0.86), Exercise Therapy: Ambulation (0.85), and Exercise Therapy: Mobility (0.84). Although all of the interventions were conceptualized for nursing across settings, these are modest levels of agreement and may reflect the practice of nursing in more structured institutional settings where exercise and activity therapies are performed by specialty rehabilitation professionals. On the other hand, the 72% round 2 response rate and the volume of written feedback received attests to the level of commitment and attention given to the task by the nurse experts. This affirms the value of seeking systematically to identify, verify, and build nursing science. PMID- 1584704 TI - Interventions related to fluid and electrolyte balance. AB - Validation of 15 fluid and electrolyte nursing interventions is a significant contribution to the development of a classification of nursing interventions, as well as the development of nursing science. Through this validation process, experts have asserted that nurses do make independent decisions and practice autonomously in the area of caring for patients with fluid and electrolyte problems. Further research is needed to carry on the work begun in this study. The enthusiasm with which this project was received by the expert raters reflects the need for nursing to reaffirm this area of practice. PMID- 1584705 TI - Dietary cholesterol enhances preneoplastic aberrant crypt formation and alters cell proliferation in the murine colon treated with azoxymethane. AB - The effect of dietary cholesterol on the development of colonic preneoplastic aberrant crypts, as well as its influence on the proliferative status of the intestinal epithelium, was investigated in mice exposed to the chemical carcinogen azoxymethane. Two strains of mice, C57BL/6J and BALB/cJ, were fed a semisynthetic diet containing 0% (control), 1.25%, or 5.00% cholesterol for eight weeks. During the first four weeks of the experiment, mice were given weekly injections of azoxymethane. Cholesterol supplementation significantly increased the formation of aberrant crypts (p less than 0.0001), enhanced the rate of cell proliferation (p less than 0.0001), altered the cell proliferative pattern, and increased crypt height (p less than 0.05) and the total number of cells per crypt (p less than 0.01) in the colonic epithelium of both mouse strains. C57BL/6J mice developed a greater number of aberrant crypts (p less than 0.0001). However, a diet-strain interaction was not observed. The results of this study indicate that dietary cholesterol enhances colon carcinogenesis in the murine colon and therefore may be an important factor in the etiology of large bowel cancer in humans. PMID- 1584706 TI - Inhibition of 7,12-dimethylbenz[a]anthracene-induced lipid peroxidation and mammary tumor development in rats by vitamin E in conjunction with selenium. AB - The effects of combined dietary vitamin E supplementation and a relatively low increase in selenium levels on 7,12-dimethylbenz[a]anthracene (DMBA) induction of lipid peroxidation in the short term and development of mammary tumors in the long term were investigated in female Sprague-Dawley rats. Control animals were fed the basal diet (20 mg/kg vitamin E and 0.6 mg/kg selenium) throughout the experiment. Three other groups received a high vitamin E diet (235 mg/kg vitamin E and 0.6 mg/kg selenium) at different times, the first two from three weeks after DMBA treatment and the other throughout the experiment. When the vitamin E diet with selenium supplementation was applied until three weeks after DMBA or until the termination of the experiment, tumor yields (tumors per rat) were significantly inhibited compared with the control group. On the other hand, delaying the supplementation of vitamin E until three weeks postcarcinogen produced no prophylactic effect. The elevation of lipid peroxidation levels observed immediately after DMBA administration was also significantly inhibited in both mammary fat pads and livers of animals in the high vitamin E group. It was therefore concluded that the inhibitory effect of vitamin E in combination with selenium on tumorigenesis might be causally related to reduction of carcinogen treatment associated with lipid peroxidation, the latter presumably playing an important role in DMBA-induced mammary carcinogenesis. PMID- 1584707 TI - The effects of topical and oral L-selenomethionine on pigmentation and skin cancer induced by ultraviolet irradiation. AB - This study was conducted to determine whether oral and/or topical selenium (Se) supplementation can reduce the incidence of acute and/or chronic damage to the skin (i.e., sunburn and pigmentation and/or skin cancer, respectively) induced by ultraviolet (UV) irradiation in mice. Groups of 38 BALB:c female mice or 16 Skh:2 hairless pigmented mice were treated with 1) lotion vehicle, 2) 0.02% L selenomethionine (SeMet) lotion, or 3) vehicle and 1.5 ppm SeMet in the drinking water. Within each group, 30 BALB:c mice or 12 Skh:2 mice were given UV irradiation (Westinghouse FS 40 bulbs) three times per week in doses of 0.575 and 0.24 J/cm2, respectively. The animals' weights and food intakes and the Se concentrations of skin and liver were measured. Skin biopsies were taken from the backs and abdomens of all animals to evaluate the relative amounts of Se and the damage by UV irradiation. Skin pigmentation was scored, and the total number of clinically detectable skin tumors per animal was counted weekly. Results showed that the skin Se concentrations in areas of application of the lotion containing SeMet were greater than those of animals given comparable oral doses, while the Se concentrations of untreated skin and liver were similar to those of animals receiving oral Se. Mice treated with Se showed no signs of toxicity and had significantly less skin damage by UV irradiation, as indicated by reduced inflammation and pigmentation and by later onset and lesser incidence of skin cancer. PMID- 1584708 TI - The effect of flaxseed supplementation on the initiation and promotional stages of mammary tumorigenesis. AB - The cancer protective effects of flaxseed suggested by our previous short-term study were tested in a long-term tumorigenesis experiment. Feeding rats 5% flaxseed flour supplemented in a high-fat diet at the promotional stage of tumorigenesis, i.e., after 7,12-dimethylbenz[a]anthracene administration, significantly reduced by 66.7% the size of the tumours that occurred. Although flaxseed feeding at the initiation stage also tended to reduce the number of tumors per tumor-bearing animal, significant differences were seen only between the group fed flaxseed throughout the experiment and the promotional group. Therefore the effect of flaxseed on mammary tumorigenesis is not consistent. Although it was speculated that the effect may be related to the lignans enterolactone and enterodiol produced in such large quantities on the ingestion of flaxseed, further studies are required to clarify the role of lignans and other flaxseed constituents in mammary tumorigenesis. PMID- 1584709 TI - No effect of adult dietary fat on tumors induced prenatally by diethylstilbestrol. AB - Strain CD-1 female mice exposed prenatally to diethylstilbestrol (DES) or vehicle were placed on semipurified diets containing 2.6%, 10%, 20%, or 29% fat by weight at four weeks of age. These mice were used as a breeding colony for a few weeks and then maintained to terminal illness on the semipurified diets. Females exposed prenatally to DES developed mammary tumors, pituitary tumors, and glandular tumors of the reproductive tract. There was no significant difference in tumor frequency between low- and high-fat dietary groups. Fewer tumors appeared in the vehicle-exposed mice, as expected, and their frequency did not differ between the dietary groups. Pregnancy reduced tumor frequency in DES exposed mice, but the incidence of pregnancy was not significantly different between low- and high-fat dietary groups. In the adult the failure of a high-fat diet to increase the frequency of reproductive system tumors induced prenatally is in marked contrast to the effectiveness of high-fat diets in promoting mammary tumors induced by carcinogens given to rats postnatally. This difference is critical in the interpretation of epidemiological studies. The relationship of dietary fat to reproductive system cancer in human populations was reviewed in comparison with these two animal models. The epidemiological literature was found to be more consistent with the animal model, showing high sensitivity to dietary fat prenatally but no significant sensitivity at the adult stage of life. PMID- 1584710 TI - Dietary micronutrients and cervical dysplasia in southwestern American Indian women. AB - American Indian women in the Southwest have high rates of cervical cancer and cervical dysplasia in contrast to low rates of cancers for other sites. Despite their high rates of cervical disease, no published information has specifically examined risk factors for cervical cancer or cervical dysplasia among American Indian women. We carried out a pilot case-control study of cervical dysplasia in southwestern American Indian women to examine the relationship of dietary intake of vitamin C, folacin, vitamin E, carotenoids, and retinol with cervical cytological abnormalities. Twenty-four-hour dietary recalls were collected from women with cervical dysplasia (n = 42) and women with normal cervical cytologies (n = 58). Macro- and micronutrient intake was estimated from these recalls utilizing food and nutrient data from the USDA Survey Nutrient Database. Although mean differences between cases and controls were not statistically significant for any of the micronutrients examined, women with low intake of vitamin C, folacin, and vitamin E were at increased risk of having cervical dysplasia when the data were analyzed as stratified for level of intake (low vs. high intake odds ratios were 3.0 for vitamin C, 3.3 for folacin, and 1.7 for vitamin E). The relationship between dietary micronutrients and cervical dysplasia among American Indian women warrants further investigation using more refined measures of dietary micronutrient intake, together with consideration of other risk factors for cervical disease. PMID- 1584711 TI - Stability of a commercially prepared fish oil (omega-3 fatty acid) laboratory rodent diet. AB - There is evidence that highly unsaturated omega-3 fatty acids present in fish oils can provide a cancer-protective effect; however, when added to laboratory rodent formulations, these fatty acids are subject to rapid and/or extensive oxidation and other chemical changes by exposure to air, light, or heat during processing of pellets or when stored for various lengths of time. An animal diet with 16% refined fish oil and 4% corn oil was commercially prepared with antioxidants (butylated hydroxytoluene and butylated hydroxyquinone in addition to alpha-tocopherol) present, and precautions were taken to prevent oxidation at all stages of production and handling. Fatty acid composition of dried powdered diet as well as freshly processed dried pellets was analyzed from four lots at the beginning and end of a 45-day feeding period. Additionally, fatty acid analyses were carried out on pellets dried by both vacuum and air techniques, and pellets were left exposed to air at room temperature for 96 hours. No statistical difference in overall fatty acid composition was observed among lots due to pelletization or drying procedures. Moreover, 4 days of exposure of pellets to air at ambient temperatures and 45 days of freezer storage had no significant effect on their fatty acid composition. It would appear that rodent diets containing omega-3 fatty acids can be reliably prepared commercially and safely substituted for diets prepared manually and in bulk on a weekly basis. PMID- 1584712 TI - Evidence for increased non-ceruloplasmin copper in early-stage human breast cancer serum. AB - We measured total serum copper and ceruloplasmin levels in pre- and postmenopausal Stage I and II breast cancer (BC) patients and omnivorous and vegetarian controls. The omnivorous groups included 14 premenopausal women [33 +/ 6 (SD) yrs] and 11 postmenopausal women (57 +/- 5 yrs), and the vegetarian groups were comprised of 12 premenopausal subjects (34 +/- 7 yrs) and 11 postmenopausal subjects (59 +/- 5 yrs). There were 13 premenopausal BC patients (39 +/- 7 yrs) and 10 postmenopausal BC patients (66 +/- 6 yrs). Fasting serum samples were taken on three consecutive days, typically four times in the year. Serum ceruloplasmin levels (g/l) were measured by nephelometry utilizing monoclonal antiserum, and total serum copper levels (mumol/l) were determined by proton-induced X-ray emission analysis. Premenopausal patients had higher serum copper levels than their controls (mean 18.7 vs. 16.6, p less than 0.03). For ceruloplasmin, the postmenopausal BC patients had significantly lower levels than pooled postmenopausal controls (0.309 vs. 0.370, p less than 0.001). The copper to-ceruloplasmin ratio was significantly higher in the pooled cancer groups than in the pooled control groups (3.69 vs. 3.21, p less than 0.001), with similar patterns in both pre- and postmenopausal classes. This high serum copper-to ceruloplasmin ratio in BC patients may reflect disordered copper metabolism in this disease, which could also have implications for the origin of, or the response to, the cancer process. PMID- 1584713 TI - Gross and microscopic changes associated with a nonthoracotomy implantable cardioverter defibrillator. AB - The pathology associated with an investigational transvenous defibrillating and sensing lead is described. The lead system had delivered a total of 865 J from the time of implantation to the time of patient death from a noncardiac cause 7 months after implantation and 1 month after his last defibrillator shock. There was mild, superficial fibrous thickening on the endothelial surface of the superior vena cava adjacent to the proximal spring electrode, which did not extend into the vessel wall. The distal portion of endocardial lead was embedded in the interventricular septum near the apex of the right ventricle, surrounded by fibrous thickening, and partially covered by endocardial tissue. Microscopically, there was a thick bed of fibrous connective tissue surrounding the lead with extensive interstitial fibrous connective tissue radiating into the adjacent myocardium. Since this pattern is different from the more generalized fibrotic scarring produced by myocardial infarction, we speculate that the mechanism for the observed interstitial fibrosis is replacement fibrosis following acute myocyte injury that resulted from prior defibrillator shocks and possibly from the trauma produced by the lead compressing adjacent myocardium during systole. Potential effects on device efficacy of these fibrotic changes at the bioelectric interface include their representing a new arrhythmia substrate, the possibility that fibrosis could increase both defibrillation and pacing thresholds, and that the inflammatory reaction may cause deterioration of intracardiac electrograms and interfere with sensing and tachycardia recognition. PMID- 1584714 TI - A special festschrift issue in honour of Zena Stein and Mervyn Susser. PMID- 1584715 TI - Epidemiology and the wider world: celebrating Zena Stein and Mervyn Susser. PMID- 1584716 TI - The contrasting effects of parental birthweight and gestational age on the birthweight of offspring. AB - Investigations on intergenerational effects on birthweight have been carried out using the data of the 1958 British National Birthday Trust Fund cohort and its follow-up to 23 years, the National Child Development Study (NCDS-4), which included information on all births to cohort members by that age. This report is directed particularly at ascertaining the independent effect of parental gestational age on babies' birthweight. The two main findings are a direct association between parental and offspring birthweight (significant for both mothers and fathers after allowing for confounding factors), but an inverse association with parental gestational age (significant only for the mothers). It is postulated that at least part of this effect is mediated through the association between maternal fetal growth rate and their babies' birthweight; the faster the rate the shorter the gestational age for a given birthweight. It was not possible to ascertain what part genetic factors played in this relationship. Larger and more informative intergenerational studies are needed to further knowledge on this question. PMID- 1584717 TI - Febrile seizures and epilepsy: the contributions of epidemiology. AB - In the past, febrile seizures were considered to be a sign of epilepsy, a disorder characterised by recurrent unprovoked seizures. Currently, febrile seizures are considered to be a benign seizure syndrome that is distinct from epilepsy. This distinction has been possible largely because of the epidemiological evidence which is presented here in the form of a two-part argument. If febrile seizures are epilepsy one might expect that: (1) following a first febrile seizure, the risk of a second febrile seizure should be similar to the risk of an unprovoked seizure (in fact, the risk of a recurrent febrile seizure is approximately 34%, whereas the risk of an unprovoked seizure after having had a febrile seizure is approximately 2% to 3%); (2) the factors that predict recurrent febrile seizures should also predict subsequent unprovoked seizures. From the available literature, young age at the time of the first febrile seizure and a family history of febrile seizures predict recurrent febrile seizures, but do not predict subsequent unprovoked seizures. By contrast, a family history of epilepsy, complex febrile seizures and neurological abnormality are associated with an increased risk of subsequent epilepsy but are not consistently associated with the risk of a recurrent febrile seizure. PMID- 1584718 TI - The epidemiology of severe injuries to children in northern Manhattan: methods and incidence rates. AB - The epidemiology of injury incidence in inner-city children has not previously been described. This study presents the methods used and the incidence rates found for severe injury (causing hospitalisation or death) in a population of 89,000 children under age 17 years in northern Manhattan, a largely poor area of New York City. The average annual incidence rate (measured from 1983 to 1987) for severe injuries to children under 17 was 846/100,000 a year. The vast majority (79%) were classified as unintentional. Nine per cent were due to assault, 3% were self-inflicted and in an additional 9% the intention was unclear. Classified by cause, the highest incidence (per 100,000/year) was found for falls (218), vehicle-related (141, primarily pedestrian), ingestion (119) and burns (110). Guns caused 3% of the injuries (27). The death rate from injury was 18.7/100,000, 36% of which was due to homicide. In an additional 28%, intentional injury was suspected. The suicide rate was 0.4/100,000. The leading causes of injury death included guns and burns (both 2.7/100,000). Compared with childhood injury rates in predominantly rural and suburban populations, the rates reported here for northern Manhattan are higher for overall injury incidence (fatal and non-fatal) and for homicide, but lower for injury mortality not due to homicide. PMID- 1584719 TI - Estimates of the prevalence of childhood seizure disorders in communities where professional resources are scarce: results from Bangladesh, Jamaica and Pakistan. AB - Although numerous estimates of the prevalence of seizure disorders in populations in the less developed world have now been published, these estimates are difficult to interpret due to lack of comparability of study methods and criteria for case definition. The results reported in this paper are from a large, collaborative study of disabilities in 2- to 9-year-old children in which standard research procedures and case definitions were used in three diverse populations (located in Bangladesh, Jamaica and Pakistan). A two-phase study design (screening followed by professional evaluations) was used in this study allowing for the professional evaluation to serve as the criterion in the estimation of prevalence, even for rare disorders. As a result, the prevalence estimates reported here have a high degree of comparability across populations and exhibit unusually strong validity for population surveys. Febrile seizures were the most common type of seizure history in all three populations, with point estimates of lifetime prevalence ranging from 10.9 to 62.8 per 1000. The lifetime prevalence rates of epilepsy (recurrent unprovoked seizures) ranged from 5.8 to 15.5 per 1000. Lifetime prevalence rates of neonatal, all provoked and all unprovoked seizures, as well as estimates of the prevalence of active epilepsy, are also reported. PMID- 1584720 TI - Epidemiology and taxonomy in mental retardation. AB - The present state of epidemiological research in relation to mental retardation is described, with particular respect to taxonomic issues. A comprehensive taxonomy is proposed, and the problems of establishing it discussed. PMID- 1584721 TI - Importance of the first day death rate in infant mortality. AB - The conventional partition of infant mortality into neonatal and postneonatal deaths, with the 28th day postpartum as the dividing line, has lost much of its epidemiological rationale in countries with low infant death rates. Infant deaths are concentrated increasingly at the start of the neonatal period: one out of three infant deaths in the United States occurs during the first 24 hours. Circumstances of early neonatal deaths differ considerably from those of later neonatal deaths. Failure to monitor separately early and late neonatal mortality can compromise the recognition of distinct epidemiological patterns. Racial disparities in the US tend to be larger for first day deaths than for any other infant deaths. Total US infant mortality declined rapidly in the 1950s and 1960s but first day deaths rose at a steady pace. Surveillance of infant mortality, whether on the national or the community level, should encompass first day, first month and first year death rates. PMID- 1584722 TI - The epidemiology of electric and magnetic field exposures in the power frequency range and reproductive outcomes. AB - Some laboratory studies have reported effects of extremely low frequency electric and magnetic fields on calcium homeostasis and pineal gland function which potentially could have consequences for reproductive health. The purpose of this review is to report results of research to date in humans on maternal, paternal and fetal exposure to the 50-60 Hz fields associated with electricity, and to propose populations, endpoints and strategies for future research. PMID- 1584723 TI - Genetic risk factors for perinatally acquired HIV-1 infection. AB - This study evaluates genetic influence on susceptibility to perinatal HIV-1 infection among 106 Black infants from New York and San Francisco born to mothers infected with HIV-1. Genes tested by molecular techniques are HLA class II loci DRB1, DPB1 and DQA1; HLA class III loci complement C4A and C4B; alpha and beta interferons; and the constant region of the T-cell receptor beta chain. Of the 106 infants analysed, 54 are infected with HIV and 52 remain uninfected at age 15 months and older. Genotypes in the HLA region appear to influence risk of HIV infection. Specifically, infants with the amino acid sequence -asp-glu-ala-val- at DPB1 positions #84-87 are more likely to be infected (P = 0.001) and infants with the allele DQA1*0102 are less likely to be infected (P = 0.031). Combinations of these two risk factors show a strong dose response (P = 0.0005). HLA DPB1 and DQA1 may play a direct role in immune response associated with HIV-1 infection, or the critical region may be located between these two genes. Characterisation of other class II HLA genes in these infants will allow more precise determination of the role of HLA loci in susceptibility to HIV-1 infection. PMID- 1584724 TI - Trisomy and age at menopause: predicted associations given a link with rate of oocyte atresia. AB - The association of trisomy with advancing maternal chronological age suggests that some aspect of physiological aging is accelerated in women with trisomic pregnancies. This paper develops a quantitative theoretical model based on the hypothesis that trisomy risk is primarily a function of the size of the oocyte pool and, in particular, that risk is increased in women with accelerated rates of oocyte atresia and hence smaller pools at given chronological ages. Since the rate of oocyte atresia is a determinant of age at menopause, this hypothesis leads to the prediction that women who have had trisomic pregnancies reach menopause earlier than women who have not. We used data relating chronological age to oocyte number, trisomy and menopause to deduce the distribution of oocyte atresia rates in all women and in women with trisomic pregnancies. Given certain simplifying assumptions, we predict that associations between trisomy and age at menopause will vary with a woman's age at the time of trisomy such that trisomies at 34-43 years will be associated with a 1-3.4 year earlier onset of menopause, while trisomies at younger or older ages will have no or little association with age at menopause. This model, while vulnerable to the uncertainties that attend its assumptions, provides a testable prediction that permits separation of one aspect of physiological age from chronological age. PMID- 1584725 TI - Decreased birthweights in infants after maternal in utero exposure to the Dutch famine of 1944-1945. AB - Using maternity records of the University of Amsterdam teaching hospital for births 1960-1984, obstetric outcomes in 1808 first-born singleton offspring of mothers born between 1 January 1944 and 30 June 1946 in The Netherlands were analysed. Most of these mothers had experienced, during intra-uterine life, a war induced famine that lasted from November 1944 to May 1945. The study was prompted by a report on increased perinatal mortality in offspring of such mothers and it aimed at describing late effects, if any, of such an exposure. Mothers exposed to famine during their first and second trimester in utero had offspring with birthweights lower than mothers not exposed to famine. The decrease in birthweight was in part due to slower fetal growth rate, in part to shorter gestation. Birthweights in the offspring of mothers exposed in their third trimester in utero were, however, not reduced. These findings in mothers exposed to famine in utero are in contrast to the effects of the famine on their mothers during their pregnancies, where third trimester exposure was associated with a reduction in birthweight. The effect of in utero exposure on birthweight persisted after control for potential confounding and intervening variables. Paradoxically, similar effects were seen in offspring of some mothers presumably not exposed to malnutrition. In this study, clear effects on reproductive outcomes are seen in the generation following an environmental exposure in utero. PMID- 1584726 TI - The contribution of maternal depressive symptoms and life events to child behaviour problems. AB - The effect of maternal depressive symptoms and stressful life events on child behaviour problems has been the focus of clinical and epidemiological research for some years. We interviewed 80 women drawn from the New York City area regarding their life events in the preceding 6 months, current levels of depressive symptoms and behaviour problems in their children. For each woman, one child between the ages of 3 to 8 was selected for study analysis. Maternal depressive symptoms and maternal life events in general, as well as undesirable events in particular, contributed independently to child behaviour problems in multivariable analyses controlling for maternal education. This association did not vary by maternal marital status, or gender or age of the child. Events judged on common sense grounds to be especially disruptive of the child's routine did not contribute to child behaviour problems, independently of maternal depressive symptoms. Future research should devote more attention to specification of the life events under study and of factors that may buffer both the mother and the child from their pathogenic effects. PMID- 1584727 TI - Genetic and developmental influences on susceptibility to epilepsy: evidence from twins. AB - This study evaluated genetic and developmental contributions to epilepsy, using data on epilepsy and multiple births in the sibships of 1981 probands with epilepsy. Prevalence of a history of epilepsy was much higher in monozygotic (MZ) than in dizygotic (DZ) co-twins of probands (35.0% vs. 3.7%), but prevalence was not significantly higher in DZ co-twins than in singleton siblings. The proportion of individuals who were MZ twins was higher among probands with epilepsy than among their non-co-twin siblings without epilepsy (odds ratio 2.5, 95% CI 1.31-4.85). However, the proportion who were DZ twins was similar among probands and unaffected siblings (odds ratio 1.0, 95% CI 0.67-1.60). These findings suggest that the increased prevalence of epilepsy in MZ co-twins of probands may be partly explained by developmental factors related to MZ twinning, rather than by their genetic identity with the probands. PMID- 1584728 TI - The central New Jersey neonatal brain haemorrhage study: design of the study and reliability of ultrasound diagnosis. AB - Over a 34-month period, 1105 newborns weighing between 501 and 2000 g at birth were enrolled in a prospective study of the aetiology and consequences of neonatal brain haemorrhage. The three participating hospitals care for approximately 85% of births in the study weight range in Middlesex, Monmouth and Ocean counties, New Jersey. Cranial ultrasonographic imaging through the anterior fontanelle was carried out a mean age of 4.9 +/- 2.2 hours, 25.5 +/- 4.8 hours and 7.2 +/- 0.8 days to detect haemorrhage and other brain lesions. In 93.2% of study infants, scans were read by two independent expert readers (blind to the clinical status of the child) with submission of the scan to a third reader in cases of disagreement. Confirmation of both presence or absence and, when present, scan of first diagnosis of germinal matrix and/or intraventricular haemorrhage (GM/IVH) by two independent readers was achieved in 76.3% of study infants. The first two readers agreed as to presence or absence of GM/IVH in 82.4% of infants (Kappa = 0.56). Interobserver agreement was affected by the reported scan quality and by the number of scans available, but not by the hospital of origin, race or birthweight of the infant. PMID- 1584730 TI - Survival and cerebral palsy in low birthweight infants: implications for perinatal care. AB - Whilst only about a third of all cerebral palsy occurs in children who had been of low birthweight, recent increases in the survival of low and very low birthweight infants have coincided with significant increases in the numbers of cerebral palsy children amongst them. This paper analyses data from the Western Australian Cerebral Palsy Register and from the Maternal and Child Health Research Data Base for stillbirths, neonatal deaths and survivors to address the issues of increased survival, cerebral palsy and timing of brain damage. The analysis is inconclusive but suggestive that both antenatal and postnatal complications are important in the increases in cerebral palsy in low birthweight infants. The good news is that this means that a certain proportion of postnatally damaged low birthweight survivors could possibly be prevented by better neonatal care. The bad news is that the remaining proportion have probably received their damage well before delivery and the possibilities for prevention are still remote. Further studies of low birthweight infants with cerebral palsy are urgently required. They should include antenatal factors, investigating the various aetiological pathways to preterm birth, randomised controlled trials of neonatal interventions and searching for better neonatal predictors of brain damage. PMID- 1584729 TI - A trial of health education aimed to reduce cigarette smoking among pregnant women. AB - Three hundred and forty-six women who reported smoking one or more cigarettes per day prior to the 20th week of gestation were recruited into a trial of health educational counselling to stop or reduce cigarette smoking. Counselling was begun at the first prenatal visit and then continued subsequently in the home. Among the 319 women included in analysis, at first follow-up visit those who received counselling smoked 1.7 fewer cigarettes a day than control women (P less than 0.05) and 10.4% had stopped smoking, compared to 5.4% in the control group (NS). Similar but not significant differences were noted at the end of pregnancy. Study effects were limited to the 284 women smoking five or more cigarettes a day at booking. This report refers primarily to them. At first follow-up visit the proportion of such women in the counselled group who ceased smoking (9.3%) was significantly greater than in the control group (2.6%; P less than 0.05). The magnitude of this difference persisted through late pregnancy (11.8% vs. 4.3%; NS) and delivery (10.6% vs. 4.7%; NS). The differences between counselled women and controls in numbers of cigarettes reported smoked at first and last prenatal follow-up visits (2.4 and 2.1) and at delivery (2.0) were all statistically significant. While there was no effect of counselling on either serum thiocyanate or end expiratory carbon monoxide, the counselled group gained slightly more weight than controls during the study (0.47 vs. 0.44 kg per week among controls; NS), and their infants had modestly higher birthweight (44 g; NS). PMID- 1584731 TI - [Counseling work with foreign families]. AB - In spite of informations about a rapid change of behavioral patterns, immigrant children, youth and families have problems to keep their identity and being understood in the guest countries. Assistance of any kind and especially counseling in intrapsychic and social conflicts has to follow special topics. There are not only language barriers, the adviser has to take care of the ethnological background and the social-cultural conditions of the home country, he has to know about loyalty mechanisms to the family of origin, to manage closeness and distance in interactional relationship. Often he has also to help children and adult persons to experience self-confidence and self-conciousness in solving psychological problems instead of helplessness and waiting for magic and mystic help. PMID- 1584732 TI - [Child and adolescent psychiatry--how, where, for whom? Questions on medical care and medical care research]. AB - Regarding the question of child psychiatry--how, where, for whom? research of medical care can provide some answers, which are referred to here. However, many questions regarding epidemiology and research of structure, use and development remain open. Because of constant urgency to take action provisional situations have to be accepted, processes have to be attended to, statements have to be examined concerning their validity and theories concerning their range. PMID- 1584733 TI - [The fairy tale of the "Marienkind"--adolescence in a fairy tale]. AB - The fairy-tale of "St. Mary's Child" has often been neglected by contemporary readers because it is said to be extremely moralistic. I try to demonstrate that it must not necessarily be seen in this way, and that its dramatic quality stems from the conflict of the super-ego and the ego. This concerns primarily the phenomenon of the lie to which the protagonist takes refuge in order to prevent the authority from intruding. I quote H. KOHUT's "one's empathy for one-self" which means that it can be an important experience (either in childhood or in therapy) to perceive that neither parents nor therapists are omniscient so that their empathy must be counter-balanced by "one's empathy for one-self". My interpretation of the fairy-tale follows this direction. PMID- 1584734 TI - [Comments on the problem of splitting in anorectic patients]. AB - The increasing number of hospitalizations of anorectic patients requires the staffs understanding for one of the most difficult problems here: the common strategy. It's failure is interpreted as a counter-transference of the patients inner processes. There are multiple factors of intra- and inter-psychic splitting, which lead to a heightened tendency of social manipulations. PMID- 1584735 TI - [Isolation of mycobacteria from sputum. Comparison of the MB Check with the radiometric and conventional method]. AB - 1179 sputum samples were investigated by the MB-Check, the conventional method and Bactec 460 to compare the recovery rate of Mycobacterium tuberculosis, the contamination rate, and time requirement for the isolation. Of the 293 positive sputa, the MB-Check detected 89,1%, Lowenstein Jensen medium 90,1%, the Bactec system 90,4%, the combination MB-Check/Lowenstein Jensen 95,9%; and the combination Bactec/Lowenstein Jensen 96,6%. The average detection times for 130 Mycobacterium tuberculosis-strains with the MB-Check slide, with the liquid medium of the MB-Check, with Lowenstein Jensen and with Bactec were 26.0, 20.4, 25.3, and 12.0 days, respectively. PMID- 1584736 TI - [Metastatic echinococcosis as a rare differential diagnosis of therapy refractory bronchitis]. AB - In a 68 year old male german patient we found a transdiaphragmatic perforation of a superinfected liver echinococcus granulosus cyst into the bronchial system as cause of a purulent bronchitis resistant to treatment. After operative removal and oversewing of diaphragm bronchitis was cured and the patient could be discharged. PMID- 1584737 TI - [Is hyposensitization still an adequate procedure in treatment of bronchial asthma?]. AB - Hyposensitization of asthmatic patients is still an open and controversially discussed question. An own randomized, single-blind study including 39 patients who were controlled twice at one year intervals by bronchial allergen challenges is demonstrated. Hyposensitization resulted in a decrease of the number of late asthmatic reactions whereas placebo was associated with an increase of this type of reaction. On the other hand only placebo induced an elevation of the specific bronchial threshold dosage for allergens, e.g. the asthma-inducing or tolerated allergen load increased by 13 to 36% (p greater than 0.005). These results which are in agreement with experiences especially of anglo-saxon authors, severe side effects in some cases as well as the improvement obtained by topic corticosteroids and mast cell stabilizers reveal hyposensitization not to be the treatment of choice for asthmatic patients. PMID- 1584738 TI - [New knowledge about exogenous allergic alveolitis]. PMID- 1584739 TI - Toxoplasma gondii: differentiation and death of bradyzoites. AB - The living parasites in Toxoplasma cysts cannot be eradicated by current therapy and maintain latent infections for many years. Relatively little is known about encysted Toxoplasma. We therefore undertook studies using mice infected with the avirulent ME 49 strain of Toxoplasma. The bradyzoites in young (12- to 17-day old) cysts contained the same organelles as did tachyzoites. The bradyzoites of older cysts (4 weeks postinoculation) had differentiated, losing certain organelles and acquiring others. Our major new finding was that in animals inoculated greater than or equal to 4 weeks previously, some bradyzoites were totally disrupted, spilling their contents (perhaps including lytic substances) into the cyst matrix. Many older bradyzoites in the same cysts lacked internal membranes and their viability was questionable, but there were also occasional parasites resembling viable tachyzoites and mature bradyzoites, organisms that might possibly initiate daughter cyst formation after cyst rupture. The life span of an individual bradyzoite may be shorter than formerly appreciated despite the prolonged course of latent infections. PMID- 1584740 TI - Studies on tsetse midgut factors that induce differentiation of blood-stream Trypanosoma brucei brucei in vitro. AB - An in vitro system for studying the transformation of bloodstream forms of Trypanosoma brucei brucei into procylic (midgut) forms is described. In this system, transformation of the parasites was stimulated by Glossina morsitans morsitans midgut homogenates at 27 degrees C but not at 4 degrees C. The transformation-stimulating capacity was irreversibly destroyed by heating the midgut homogenates at 60 degrees C for 1 h. A correlation was established between the transformation activity of the midgut homogenates and trypsin activity. The protease inhibitors (soybean trypsin inhibitor and N-p-tosyl-L-lysine chloromethyl-ketone) inhibited trypsin activity and completely blocked the transformation of the parasites. Furthermore, the midgut homogenates could induce transformation only in the presence of blood. These results provide evidence for the involvement of trypsin or trypsin-like enzymes within the tsetse midgut in stimulation of the transformation of bloodstream trypanosomes. PMID- 1584741 TI - T-lymphocytes in experimental Leishmania amazonensis infection: comparison between immunized and naive BALB/c mice. AB - Highly susceptible naive BALB/c mice or mice that had previously been immunized i.v. with solubilized homologous antigen (partially resistant) were infected with Leishmania amazonensis. Histologically, the main differences between the two groups were lymphocytic infiltration and macrophage activation. Assays of T-cell function at 3 and 10 weeks after infection revealed that purified T-cells did not proliferate following treatment with leishmania antigen. A mitogenic anti-CD3 monoclonal antibody (mAb) failed to activate T-cells after 3 weeks of infection as judged by proliferation and IL-2 secretion assays. After 10 weeks of infection, anti-CD3 mAb fully activated T-cells to proliferation and IL-2 secretion. On the other hand, T-cells released IL-3 in response to leishmania antigen, anti-CD3 mAb and anti-Thy1 mAb at 3 and 10 weeks post-infection. Surprisingly, a mitogenic anti-Thy 1 mAb (G7) fully activated T-cells even at 3 weeks of infection as judged by proliferative and IL-2 secretion assays. No significant differences were found in the proliferative or interleukin secretory responses of T-cells from animals that had been infected in either the presence or the absence of prior immunization. Since the Thy1 triggering pathway has different accessory cell and cytokine requirements than does the CD3: TCR lymphocyte activation pathway, it is possible that immunization was more effective in changing the cellular interactions of the T-lymphocyte than in altering its intrinsic capabilities. PMID- 1584742 TI - Cloning and characterization of a repetitive sequence from Pneumocystis carinii. AB - Four repetitive sequence clones measuring 10.9-23.4 kb in length were isolated from the genomic library of Pneumocystis carinii. Restriction enzymes mapping and cross-hybridization studies revealed that these clones are interrelated and that they derive from the common repeat unit, which is specific for P. carinii. Dot blot analysis suggested that the copy number of the repeat sequence is about 100, assuming that the genome size is 1.5 x 10(7) bp. Interestingly, the repetition unit extended over at least 23.4 kb and included long, 5.2-kb inverted repeats, for example, A-B-A'-C, in which A' is the inversion of A. PMID- 1584743 TI - Effects of reactive oxygen intermediate scavengers on the antitoxoplasmic activity of activated macrophages. AB - Obioactin, Lonomycin A, muramyl dipeptide, and scavengers of hydrogen radicals and of singlet oxygen were used to study the participation of.OH and 1O2 in the killing of Toxoplasma in cultures of glycogen-induced peritoneal macrophages. Both the scavengers of OH (diazabicyclooctane and histidine) and those of 1O2 (mannitol and sodium benzoate) failed to inhibit the multiplication of Toxoplasma in macrophages that were incubated with either Obioactin, Lonomycin A, or MDP. The results of these experiments demonstrate the apparent lack of an inhibitory effect of.OH and 1O2 on the multiplication of Toxoplasma, whereas the scavengers alone inhibited the growth of the parasites. PMID- 1584744 TI - Eimeria bovis in cattle: colostral transfer of antibodies and immune response to experimental infections. AB - IgM, IgG1, and IgG2 antibodies to Eimeria bovis first-generation merozoite antigens were determined by enzyme-linked immunosorbent assay and Western blotting in naturally infected cows and in their offspring before and after the uptake of colostrum. In addition, calves were examined following experimental primary and challenge infections. Neonate calves received maternal antibodies via colostrum. All isotypes determined were transmitted, but only IgG1 was concentrated in the colostrum and it occurred at significantly increased levels in sera from the calves as compared with those from the respective dams. Recognition patterns (Western blotting) displayed by related maternal serum and colostrum and those shown by calves that had ingested colostrum were very similar, but marked variations occurred between individual pairs. Experimental infection of 15-week-old calves with 0.7 x 10(5) oocysts caused strong protective immunity against a challenge with 1 x 10(5) oocysts. In contrast, animals that had undergone a weak intercurrent infection were not protected. Experimental infections induced a considerable increase in IgG1 and IgG2 antibody levels, whereas IgM values increased only slightly. The spectrum of merozoite antigens recognized by the sera increased markedly after experimental infection, although high individual variations were found in the calves. However, there was no correlation between the levels of any specific antibody or the recognition patterns and the status of immunity to a severe challenge. PMID- 1584745 TI - An unidentified Toxoplasma-like tissue cyst-forming coccidium in a cat (Felis catus). AB - An unidentified coccidium was found in the brain and the heart of a 6-year-old female cat. Tissue cysts measured 40-130 x 40-112 microns and contained hundreds of bradyzoites measuring 4.2-5.2 x 1.2-1.8 microns. The cyst wall was 0.26-0.53 microns thick. Tissue cysts reacted positively with anti-Toxoplasma gondii serum but not with anti-Neospora caninum serum in an immunohistochemical test. Ultrastructurally, the cyst was aseptate and contained banana-shaped bradyzoites. Micronemes and rhoptries in bradyzoites were unlike those found in T. gondii bradyzoites. In the unidentified coccidium, the micronemes were arranged in rows and the rhoptries extended from the anterior tip to the posterior end. PMID- 1584746 TI - Stage-specific responses following infection with Theileria annulata as evaluated using ELISA. AB - An enzyme-linked immunosorbent assay (ELISA) using sporozoite, schizont and piroplasm antigens was developed to study the immune response of animals that had been immunised with either Theileria annulata sporozoites or schizont-infected cells and then challenged with sporozoites. The aim was to identify the most suitable antigen for a routine screening test and to compare the sensitivity of the latter with that of the indirect fluorescent antibody test (IFAT). As determined by ELISA, cattle produced antibodies to all three antigens, regardless of the method of immunisation. The schizont antigen was the least sensitive, whereas the sporozoite antigen displayed high pre-inoculation values. In contrast, the piroplasm antigen exhibited low non-specific pre-infection levels and high post-immunisation and post-challenge values according to both ELISA and IFAT. Therefore, the latter was though to be the most appropriate antigen for use in ELISA. PMID- 1584747 TI - Ultrastructural study of the host-parasite relationship of trypanosomatids in the housefly. AB - The course of experimental oral infection of Musca domestica with Herpetomonas samuelpessoai and two new isolates from houseflies was followed for up to 40 days using optical and electron microscopy. The fly's rectum was found to be the preferential site of colonization by flagellates, mainly at places near papillar insertions but not on the papillae themselves. Midgut infection was transient, and infection of the crop did not last longer than 1 week. Promastigotes were the predominant colonizing forms and could be seen either free in the gut lumen or attached via hemidesmosomes to the rectum wall. Adherent flagellates exhibited flagellar projections and surface membrane blebs. Many flagellates displayed longitudinal body foldings yielding star-like images in cross sections. Opisthomastigotes could be seen in small numbers as free swimmers, mainly in the rectum. PMID- 1584748 TI - The effects of Nosema algerae on the development of Plasmodium yoelii nigeriensis in Anopheles stephensi. AB - Experimental simultaneous infections of Anopheles stephensi (Diptera: Culicidae) with Nosema algerae (Microsporida: Nosematidae) and Plasmodium yoelii nigeriensis under standardized laboratory conditions showed partial suppression of the malaria parasite. At 9 days after an infective bloodmeal, the oocysts in the midgut were counted; 12.1%-66.6% of the double-infected mosquitoes exhibited no oocysts, whereas only 4.5%-12% of the control group showed no oocysts. The mean reduction in oocyst numbers under the influence of Nosema was 84.68%. At 14 days after infection with Plasmodium, the amount of sporozoites was examined; their mean reduction in eight experiments was 70%. PMID- 1584749 TI - Potential anti-echinococcal activity of alkylaminoethers. AB - Trans 2-phenoxy cyclohexanol ethers (IA, IIA, IIIA, IVA, VA, and VIA), the cyclohexanol analog (IB) and one coumarinic compound (IC) were obtained and their activity against Echinococcus multilocularis metacestodes was studied and compared with that of trifluoperazine (TFP). All of these compounds are analogous to IA and belong to three classes. Class A comprises trans 2-phenoxycyclohexanol aminoethers whose alkylaminoether group varies; compound VIA bears one more methylene in its aminoether group than does compound IA. Class B consists of one compound exhibiting no phenoxy function. Class C comprises one coumarinic analog. In vitro assays were performed using metacestodes whose protoscoleces were attached to the germinal layer in open and in closed vesicles. Compounds IA and IIA exhibited the highest activity, but it was lower than that displayed by TFP under the same conditions. Compound IA was tested in an in vivo assay in jirds (50 mg/kg/daily beginning at 80 days p.i.); it produced results that were analogous to those obtained using TFP without inducing the neuroleptic effect associated with the latter. After 40-90 days' treatment, the percentage of diminution in the entire parasitic mass in the jirds that survived minimal treatment (71%) was about 41% as compared with that in untreated jirds. Histologic examination of the parasites in treated jirds revealed numerous dead protoscoleces and some parasitic dedifferentiated cells. This parasitic response may indicate that in alveolar echinococcosis, these drugs exhibit only a parasitostatic effect. PMID- 1584750 TI - The effect of dimethylsulfoxide on the tegumental brush border of the cestode Hymenolepis diminuta. AB - Dimethyl sulfoxide (DMSO), commonly used for cryoprotection or for the solvation of cytoskeleton-modifying drugs, causes changes in the topology of the plasma membrane of the tegumental brush border in the tapeworm Hymenolepis diminuta; however, relatively long exposures of high concentrations are required. In tapeworms treated with DMSO concentrations of greater than or equal to 1% in the present study, the interaction of the tegumental surface membrane with the underlying cytoskeleton may have been disrupted at focal points in the brush border, resulting in a partial loss of the membrane anchoring required for the structural integrity of the brush border. Blebbing of the tegumental surface was prominent only after exposure to 1% DMSO for 20 h in in vitro culture with RPMI 1640, and vesiculation of the membrane along the microvillar (microtriche) shafts, which may have been related to the in vitro conditions, was amplified by the presence of concentrations of greater than or equal to 1% DMSO in the incubation medium. The tegumental response to DMSO was not uniform but regional, consistently appearing to be more prevalent on the distal aspects of each proglottid rather than on the edge proximal to the scolex. Blebbing and vesiculation were not seen on the basal aspect of the tegument, including the basal ectocytoplasmic plasma membrane, the perikarya, and the internuncial processes. Microvillar core bundles of actin microfilaments persisted following 8 h in vitro exposure to all three concentrations of DMSO tested (0.1%, 1%, 5%); however, only in tapeworms that were treated in vitro with 5% DMSO for greater than or equal to 8 h did core microfilament bundles appear to lose the rigidly straight and parallel organization characteristic of control tapeworms that were incubated either in the absence of DMSO or with 0.1% DMSO. Other components of the brush border cytoskeleton (i.e., microvillar caps, junctional tubules, and tunics) appeared unaffected by DMSO except at foci where blebbing occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584751 TI - The expulsion of Echinostoma trivolvis (Trematoda) from ICR mice: scanning electron microscopy of the worms. AB - Echinostoma trivolvis adults are rejected from ICR mice within 3 weeks postinfection (p.i.) but are retained in golden hamsters for greater than 15 weeks. The present study used scanning electron microscopy (SEM) to examine worm topography in ICR mice, particularly that of the collar spines, and to correlate worm loss with tegumentary changes. The topography of the worm in ICR mice was similar to that observed in previous studies on this echinostome in domestic chick embryos, chickens, and golden hamsters. Observations were made on the pattern of collar spines in 115 worms from ICR mice at 3-14 days p.i. All worms examined at 3 days exhibited extended spines, whereas about 70% of the worms examined at 14 days displayed retracted or missing spines. Eight worms from golden hamsters examined at 14 days p.i. showed extended collar spines. The retraction or loss of collar spines may play a role in the expulsion of E. trivolvis from ICR mice. PMID- 1584752 TI - On the infectivity of early third-stage Brugia larvae isolated from the abdomen of Aedes aegypti. AB - Third-stage larvae (L3) of Wuchereria bancrofti, Brugia malayi and B. pahangi are known to be recovered not only from the head and thorax but also from the abdomen of dissected vector mosquitoes. For epidemiological reasons, was of interest to determine whether L3 larvae from the abdomen of the vector would be infectious for the final host. Early abdominal L3 larvae of B. pahangi isolated as early as on day 7 post-infection (p.i.) from Aedes aegypti were injected s.c. into five male Meriones unguiculatus. Four of the five jirds were microfilaria-positive after 67 days. PMID- 1584753 TI - A new screening assay for antigiardial compounds: effects of various drugs on the adherence of Giardia duodenalis to Caco2 cells. PMID- 1584754 TI - Analysis of Theileria parva immunodominant schizont surface antigen by two dimensional polyacrylamide gel electrophoresis and immunoblotting. PMID- 1584755 TI - MELAS mutation in mtDNA binding site for transcription termination factor causes defects in protein synthesis and in respiration but no change in levels of upstream and downstream mature transcripts. AB - The pathogenetic mechanism of the mitochondrial tRNA(LeuUUR) gene mutation responsible for the MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) syndrome was investigated in transformants obtained by transfer of mitochondria from three genetically unrelated MELAS patients into human mitochondrial DNA (mtDNA)-less (rho 0) cells. Marked defects in mitochondrial protein synthesis and respiratory activity were observed in transformants containing virtually pure mutant mtDNA, as compared to the parent of the rho 0 cells (the 143B cell line) or to transformants containing exclusively wild-type mtDNA, derived from one of the patients or a maternally related asymptomatic individual. A striking protective effect against the mutation was exerted in the transformants by levels of residual wild-type mtDNA above 6%. The MELAS mutation occurs within the mtDNA binding site for a protein factor (mTERF) that promotes termination of transcription at the 16S rRNA/tRNA(LeuUUR) gene boundary. A marked decrease in affinity of purified mTERF for the mutant target sequence was observed in in vitro assays. By contrast, RNA transfer hybridization experiments failed to show any significant change in the steady-state amounts of the two rRNA species, encoded upstream of the termination site, and of the mRNAs encoded downstream, in the transformants carrying the MELAS mutation. PMID- 1584756 TI - Alternative usage of initiation codons in mRNA encoding the cAMP-responsive element modulator generates regulators with opposite functions. AB - The cAMP-responsive-element modulator (CREM) gene encodes both antagonists (CREM alpha/beta/gamma) and an activator (CREM tau) of cAMP-responsive transcription by alternative splicing. In adult mouse brain a predominant 21-kDa protein, not corresponding to any previously characterized transcript, is detected with specific CREM antibodies. A developmental switch occurs in brain as expression changes at birth from CREM alpha/beta to the 21-kDa protein. We show that the 21 kDa protein corresponds to S-CREM (short CREM), a protein produced by the use of an internal AUG initiation codon in the CREM tau transcript. S-CREM shares with the other CREM proteins the basic DNA-binding and leucine-zipper dimerization domain. S-CREM functions as a transcriptional repressor of cAMP-induced transcription. Thus, two proteins with opposite functions are generated by alternative translation using two AUG codons within the same reading frame. PMID- 1584757 TI - Phosphorylation sites in the amino-terminal region of mouse p53. AB - Phosphorylation is an attractive mechanism for regulating the functions of p53. The p34cdc2 kinase, which is involved in regulation of the cell cycle, phosphorylates serine-315 of human p53 in vitro. Casein kinase II phosphorylates serine-389 of mouse p53 in vitro. The amino-terminal region of mouse p53 contains a cluster of potential serine phosphorylation sites. Those sites have been proposed to be sites for phosphorylation by a double-stranded DNA-dependent kinase (DNA-PK) from HeLa cells and can be dephosphorylated by protein phosphatase 2A. To identify in vivo phosphorylation sites in the amino-terminal region of mouse p53, we mutated potential phosphorylation sites and analyzed the mutant proteins by tryptic phosphopeptide mapping. We identified serine-7, -9, 18, and -37 as in vivo phosphorylation sites. We further showed that mouse p53 expressed in bacteria is phosphorylated by DNA-PK on amino-terminal serine residues in vitro. PMID- 1584758 TI - Transformation and transactivation suppressor activity of the c-Jun leucine zipper fused to a bacterial repressor. AB - Transcription factor c-Jun appears to be a nuclear target of the Ras-induced signal transduction pathway. In fact, some experiments show that transforming forms of the Ras protein cooperate with Jun in transcriptional activation mediated by an AP-1 site and others indicate that the two oncoproteins cooperate in cellular transformation. Although it is likely that intracellular signaling systems activated by Ras might act directly on c-Jun by inducing specific phosphorylation, it is unclear how c-Jun participates in the transformation process. Here, we present results obtained with a LexA-Jun zipper fusion that lacks both the transcriptional activation domains and the basic region of the DNA binding domain of c-Jun and contains only the intact leucine-zipper domain. This fusion product has a dominant negative effect on the transcriptional activation elicited by phorbol esters, c-Jun, c-Fos, Ras and E1A on an AP-1-responsive site. An analogous LexA-Fos zipper fusion has similar effects on transcriptional induction. The LexA-Jun zipper fusion acts further as a transformation suppressor, since it causes the generation of nontransformed revertants of ras transformed cells. This effect is likely to be elicited by the dimerization potential of the Jun leucine zipper trapping cellular Jun and/or Fos in a protein complex unable to bind to DNA. These data implicate further that Ras-mediated transformation involves functional transcription factor AP-1 and that it is possible to interfere with cell transformation by interfering simply with the dimerization of transcription factors involved in the transformation process. PMID- 1584759 TI - Pasteurella multocida toxin is a potent inducer of anchorage-independent cell growth. AB - The growth of many normal cells requires contact with an adhesive substratum, a requirement that is frequently abrogated in the transformed phenotype. We have explored pathways that can lead to the anchorage-independent growth of cultured Rat-1 fibroblasts. Pasteurella multocida toxin (PMT), a 146-kDa mitogenic protein, caused a striking increase in the formation of colonies (greater than 200 microns) from single cells in soft agar. The magnitude of the effect of PMT was greater than that achieved by epidermal growth factor or platelet-derived growth factor. The toxin was extremely potent, with half-maximal and maximal effects observed at 1 and 10 pM PMT, respectively. This concentration dependence of the action of the toxin is similar to that for the stimulation of DNA synthesis in adherent cultures of the cells. Stimulation of colony formation could be achieved by a transient exposure of the cells to PMT and it was blocked by methylamine, indicating that the toxin enters the cells to act. Colony formation was stimulated equally by native and recombinant PMT, but a truncated version (33.5 kDa) of the recombinant toxin was ineffective. PMT antiserum blocked colony formation in response to PMT. In the Rat-1 cells, PMT stimulated the phospholipase C-mediated hydrolysis of inositolphospholipids, as indicated by the stimulation of inositol phosphate release, Ca2+ mobilization, and phosphorylation of a protein kinase C substrate. The results indicate that the deregulation of signal-transduction pathways as elicited by an intracellularly acting bacterial toxin can induce a malignant phenotype. PMID- 1584760 TI - Selective manipulation of the human T-cell receptor repertoire expressed by thymocytes in organ culture. AB - A recently described organ culture system for human thymocytes is shown to support the generation of a diverse T-cell receptor repertoire in vitro: thymocytes of the alpha beta lineage, including representatives of the V beta families 5.2/5.3, 6.7, and 8, accounted for the majority of T-cell receptor positive cells throughout a 3-week culture period. Thymocytes bearing gamma delta receptors were also identified, particularly among the CD4 CD8 double-negative subset. The T-cell receptor repertoire expressed in organ culture responded to experimental manipulation with staphylococcal enterotoxins. Staphylococcal enterotoxin D (a powerful activator of human peripheral T cells expressing V beta 5.2/5.3 receptors) caused a marked reduction of V beta 5.2/5.3 expression, as determined with the V beta-specific antibody 42/1C1. Evidence is presented that this loss of V beta 5.2/5.3 expression resulted from the selective deletion of activated thymocytes by apoptosis, in concert with T-cell receptor modulation. These effects of staphylococcal enterotoxin D were specific (since staphylococcal enterotoxin E did not influence V beta 5.2/5.3 expression) and V beta-selective (since expression of V beta 6.7 remained unaffected by staphylococcal enterotoxin D). On the basis of these observations, we suggest that thymic organ culture provides a powerful approach to study the generation of the human T-cell repertoire. PMID- 1584761 TI - Functional domains in Fok I restriction endonuclease. AB - The PCR was used to alter transcriptional and translational signals surrounding the Flavobacterium okeanokoites restriction endonuclease (fokIR) gene, so as to achieve high expression in Escherichia coli. By changing the ribosome-binding site sequence preceding the fokIR gene to match the consensus E. coli signal and by placing a positive retroregulator stem-loop sequence downstream of the gene, Fok I yield was increased to 5-8% of total cellular protein. Fok I was purified to homogeneity with phosphocellulose, DEAE-Sephadex, and gel chromatography, yielding 50 mg of pure Fok I endonuclease per liter of culture medium. The recognition and cleavage domains of Fok I were analyzed by trypsin digestion. Fok I in the absence of a DNA substrate cleaves into a 58-kDa carboxyl-terminal and 8 kDa amino-terminal fragment. The 58-kDa fragment does not bind the DNA substrate. Fok I in the presence of a DNA substrate cleaves into a 41-kDa amino-terminal fragment and a 25-kDa carboxyl-terminal fragment. On further digestion, the 41 kDa fragment degrades into 30-kDa amino-terminal and 11-kDa carboxyl-terminal fragments. The cleaved fragments both bind DNA substrates, as does the 41-kDa fragment. Gel-mobility-shift assays indicate that all the protein contacts necessary for the sequence-specific recognition of DNA substrates are encoded within the 41-kDa fragment. Thus, the 41-kDa amino-terminal fragment constitutes the Fok I recognition domain. The 25-kDa fragment, purified by using a DEAE Sephadex column, cleaves nonspecifically both methylated (pACYCfokIM) and nonmethylated (pTZ19R) DNA substrates in the presence of MgCl2. Thus, the 25-kDa carboxyl-terminal fragment constitutes the Fok I cleavage domain. PMID- 1584763 TI - Nuclear translocation of viral Jun but not of cellular Jun is cell cycle dependent. AB - The Jun protein is a transcription factor of the AP-1 complex, and it is concentrated in the cell nucleus. While the cellular Jun protein is transported into the nucleus in a cell-cycle-independent fashion, the oncogenic viral version of the protein translocates into the nucleus most rapidly during the G2 phase of the cell cycle and only slowly during G1 and S phases. This cell cycle dependence of nuclear transport has been mapped to the cysteine to serine mutation in the carboxyl-terminal portion of viral Jun. We have identified a complex nuclear translocation signal located in the basic region of viral Jun. This signal has the sequence ASKSRKRKL. A peptide of this sequence synthesized in vitro and conjugated to IgG can mediate cell-cycle-dependent translocation of the microinjected conjugate from the cytoplasm into the nucleus. The nuclear translocation signal has two functional domains. The pentapeptide RKRKL is sufficient as a cell-cycle-independent nuclear address. The entire signal is needed for cell-cycle-dependent nuclear translocation. The amino-terminal tetrapeptide contains the cysteine to serine substitution responsible for cell cycle dependence. Deletion analysis of the Jun protein suggests that the nuclear translocation signal identified in the basic region is required for nuclear translocation of Jun and may be the only such signal in the Jun molecule. PMID- 1584762 TI - The FixL protein of Rhizobium meliloti can be separated into a heme-binding oxygen-sensing domain and a functional C-terminal kinase domain. AB - Transcription of nitrogen fixation (nif and fix) genes in Rhizobium meliloti is induced by a decrease in oxygen concentration. The products of two genes, fixL and fixJ, are responsible for sensing and transmitting the low-oxygen signal. The proteins encoded by fixL and fixJ (FixL and FixJ, respectively) are homologous to a family of bacterial proteins that transduce environmental signals through a common phosphotransfer mechanism [David, M., Daveran, M., Batut, J., Dedieu, A., Domergue, O., Ghai, J., Hertig, C., Boistard, P. & Khan, D. (1988) Cell 54, 671 683]. FixL, the oxygen sensor, is a membrane protein. It has previously been shown that a soluble derivative of FixL, FixL*, is an oxygen-binding hemoprotein and a kinase that autophosphorylates and also phosphorylates FixJ [Gilles Gonzalez, M. A., Ditta, G. S. & Helinski, D. R. (1991) Nature (London) 350, 170 172]. In this work, deletion derivatives of fixL* were constructed and overexpressed in Escherichia coli, and the truncated proteins were purified. We show that a fragment of FixL from amino acid residue 127 to residue 260 binds heme, retains the ability to bind oxygen, and has no detectable kinase activity. A C-terminal fragment of FixL, beginning at residue 260, fails to bind heme but is active as a kinase. We also demonstrate that anaerobiosis results in an enhancement of FixL* autophosphorylation and FixJ phosphorylation activities in vitro. Finally, we show that the heme-binding region of FixL is required in vitro for oxygen regulation of its kinase activities. PMID- 1584764 TI - Selection-induced mutations occur in yeast. AB - Selection-induced mutations are nonrandom mutations that occur as specific and direct responses to environmental challenges and primarily in nondividing cells under conditions of intense prolonged selection. Selection-induced mutations have been shown to occur at six loci in Escherichia coli, but their existence has not previously been demonstrated in any eukaryotic organism. Here it is shown that selection-induced mutations occur at the HIS4 locus in the eukaryotic microorganism Saccharomyces cerevisiae. PMID- 1584765 TI - Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N- and/or C terminal tails. AB - This study describes genomic rearrangements near the 3' end of the epidermal growth factor receptor (EGFR) gene in eight glioblastomas displaying coamplification and expression of both normal and rearranged EGFR. In four of these cases, it was possible by PCR to amplify tumor EGFR cDNA, which allowed sequence determination of the 3' transcript alterations associated with the rearrangements. Such analysis revealed that the four cases have in common a deletion of 255 bases that encode a portion of the receptor's cytoplasmic domain. The remaining four cases revealed genomic rearrangements in the same region of the gene as those described above and revealed aberrant EGFR transcripts lacking the same 255 bases determined to be missing in the sequenced EGFR cDNAs as well as large regions of contiguous downstream sequences. Therefore, all of the eight cases described here express transcripts that do not encode large C-terminal, intracellular portions of the receptor. In three of the eight cases, the EGFR transcripts displaying a 3' alteration also displayed a 5' inframe deletion of sequences encoding a portion of the extracellular domain, and for one of the corresponding patients it was possible to determine that the two transcript alterations were acquired as separate events. We have now detected the 5' and/or 3' alterations in 21 of 32 cases of glioblastoma with EGFR amplification; no genetic alterations have been detected in glioblastomas without EGFR amplification. In combination with previously published reports, these data suggest the in vivo evolution of EGFR toward an increasingly oncogenic potential through gene amplification with subsequent and successive gene alterations. PMID- 1584766 TI - Golgi retention of a trans-Golgi membrane protein, galactosyltransferase, requires cysteine and histidine residues within the membrane-anchoring domain. AB - Galactosyltransferase (GT; UDPgalactose:beta-D-N-acetylglucosaminide beta-1,4 galactosyltransferase, EC 2.4.1.22) is a type II membrane-anchored protein composed of a short N-terminal cytoplasmic tail, a signal/membrane-anchoring domain, and a stem region followed by a large catalytic domain including the C terminus. To identify the peptide segment and key amino acid residues that are critical for Golgi localization of GT, the expression vector pGT-hCG was designed to encode the entire GT molecule fused to the C-terminal region of human chorionic gonadotropin alpha subunit (hCG alpha) as a reporter. COS-1 cells transfected with pGT-hCG expressed the chimera in the Golgi region, as detected by immunofluorescence microscopy using anti-hCG antibodies. Two deletion mutants, delta tail and delta stem, which are lacking most of the N-terminal cytoplasmic tail or 10 amino acids immediately after the membrane-anchoring domain, were localized in the Golgi. Replacement mutations of the membrane-anchoring domain of GT showed that the second quarter of the transmembrane domain or Cys29-Ala30 Leu31-His32-Leu33 is necessary for GT to be retained in the Golgi. Furthermore, the point mutants Cys29----Ser29 and His32----Leu32 were partially transported to the plasma membrane, whereas an Ala30-Leu31----Phe30-Gly31 mutant was localized in the Golgi. Finally, a double mutant, Cys29/His32----Ser29/Leu32, was found to be transported efficiently to the plasma membrane. The signal-anchoring domain of the transferrin receptor, a type II plasma membrane protein, was then replaced by portions of the GT transmembrane domain. Although the Cys-Xaa-Xaa-His sequence by itself cannot retain the transferrin receptor in the Golgi, the cytoplasmic half of the transmembrane domain of GT was partially capable of retaining the transferrin receptor in the Golgi. These results suggest that the cytoplasmic (or N-terminal) half of the transmembrane domain of GT contributes to the Golgi retention signal and that particularly Cys29 and His32 in this region are critical for GT to be retained in the Golgi. PMID- 1584767 TI - Saturable binding of halothane to rat brain synaptosomes. AB - The hypothesis that volatile anesthetics act directly on or bind specifically to membrane proteins remains controversial. In earlier in situ electron probe microanalysis studies in cardiac muscle we showed preferential partitioning of halothane into mitochondria. To determine whether partitioning represents saturable binding or simple solubility, a photoaffinity labeling method was developed for halothane to examine binding in rat brain synaptosomes. Radioligand binding assays were then used to determine binding parameters for this important inhalational anesthetic. UV-light exposure of synaptosomes incubated with clinical concentrations of [14C]halothane resulted in sufficient labeling to allow characterization of binding sites. Analysis of saturation and competition curves showed that greater than 60% of [14C]halothane photolysis product binding to synaptosomes was specific, with low affinity (Kd = 0.49 +/- 0.16 mM) and high binding site concentration (Bmax = 1.87 +/- 0.75 nmol/mg of protein). Halothane photoaffinity labeling was partially inhibited by isoflurane (20%), chloroform (44%), 2-bromotrifluoroethane (20%), and dichlorotrifluoroethane (20%) but not by ethanol. The Kd measured with this photoaffinity approach is similar to the concentration of halothane required to produce anesthesia in rats. PMID- 1584768 TI - Heat shock protein Hsp60-reactive gamma delta cells: a large, diversified T lymphocyte subset with highly focused specificity. AB - Previously, we detected a subset of gamma delta T cells in the newborn mouse thymus that responded to the mycobacterial heat shock protein Hsp60, as well as with what seemed to be a self-antigen. All of these cells expressed V gamma 1, most often in association with V delta 6+. It was not clear, however, whether similar, mature gamma delta cells with Hsp60 reactivity are common outside of the thymus, or rather, whether they are largely eliminated during development. From the data presented here, we estimate that gamma delta cells responding to Hsp60 comprise 10-20% of normal splenic and lymph node gamma delta T cells. Such cells, derived from adult spleen, always express a V gamma 1-J gamma 4-C gamma 4 gamma chain, although not all cells with this gamma chain show Hsp60 reactivity. Many of these V gamma 1+ cells also express V delta 6-J delta 1-C delta, though fewer than in V gamma 1+ cells from the newborn thymus. Extensive diversity is evident in both the gamma and delta chain junctional amino acids of the receptors of these cells, indicating that they may largely develop in the thymus of older animals or undergo peripheral expansion. Finally, we found that all such cells responding to both a putative self-antigen and to mycobacterial Hsp60 respond to a 17-amino acid synthetic peptide representing amino acids 180-196 of the Mycobacterium leprae Hsp60 sequence. This report demonstrates that a large subset of Hsp60-reactive peripheral lymphoid gamma delta T cells preexists in normal adult mice, all members of which respond to a single segment of this common heat shock protein. PMID- 1584769 TI - Evidence for a functional receptor for cyclosporin A on the surface of lymphocytes. AB - Cyclosporin A (CsA) is an immunosuppressive agent that inhibits the synthesis of lymphokines by T lymphocytes at the level of transcription. A cytoplasmic protein, cyclophilin, is the most thoroughly studied CsA-binding protein, but its ubiquitous presence in cells of all types raises questions about its role in immunosuppression. In an attempt to ascertain the presence of a cell surface receptor, we synthesized two polyvalent macromolecular CsA derivatives, CsA-BBa ovalbumin and CsA-BBa-aminodextran (CBD), from the product of the photochemical reaction of CsA and 4-benzoylbenzoic acid (CsA-BBa). (i) They inhibited the peptidylprolyl cis-trans isomerase activity of cyclophilin and the synthesis of interleukin 2 by phorbol ester-activated EL-4 cells. (ii) CBD also inhibited interleukin 2 secretion by Con A-activated T-cell-enriched mouse splenocytes. 4 Benzoylbenzoic acid (BBa)-aminodextran and aminodextran were inactive. (iii) Direct binding and competition studies with [3H]CsA indicated that CBD does not enter EL-4 cells (i.e., it acted at the surface). (iv) CBD caused agglutination of EL-4 cells, murine B and T lymphocytes, human thymocytes, and two T-cell hybridomas. Agglutination was inhibited by a monoclonal antibody to CsA and by CsA and CsA-BBa, but not by BBa. No agglutination was seen with BBa-aminodextran or aminodextran. HeLa cells, Vero (monkey kidney) cells, a mouse plasmacytoma, COS cells, and a poorly differentiated B-cell lymphoma were not agglutinated. (v) EL-4 cells failed to be agglutinated after treatment with trypsin or chymotrypsin. Specific agglutination was again possible after incubation for 5 h at 37 degrees C in the absence of enzyme. (vi) CBD covalently linked to crosslinked agarose beads inhibited interleukin 2 production by phorbol ester stimulated EL-4 cells. No activity was seen if cell-to-bead contact was prevented by a 0.02-microns microporous filter that did not interfere with the passage of CBD. Our findings support the presence of a functional receptor on the surface of selected cells of the immune system. PMID- 1584770 TI - Immunostimulatory human urinary protein. AB - We have previously extracted a protein from inflammatory mouse granuloma that fully protects normal mice against lethal Listeria monocytogenes infection. We now report that polyclonal antibodies directed against this protein react with a human urinary fraction that also provides full protection of normal mice against L. monocytogenes. Murine monoclonal antibodies completely inhibit the protective activity of the human urinary fraction. We have purified to apparent homogeneity a human glycoprotein of 43 kDa (HGP.43), pI = 3.2 +/- 0.2. HGP.43 injected i.v. at 250 micrograms/kg fully protected mice against a lethal inoculum of L. monocytogenes. Such resistance followed injection of HGP.43, 4 days before and, still significantly, 8 hr after Listeria infection. In scid mice lacking T and B cells, similar resistance to L. monocytogenes was observed. Inflammatory murine macrophages became cytostatic against Lewis carcinoma cells after incubation with 1.5 nM HGP-43. PMID- 1584771 TI - Cloning of the rat gene encoding choline acetyltransferase, a cholinergic neuron specific marker. AB - The neurotransmitter acetylcholine is synthesized by choline acetyltransferase (ChAT; EC 2.3.1.6). Since the expression of ChAT in the nervous system is restricted to cholinergic neurons, it serves as a specific marker for these neurons. In Alzheimer disease, ChAT activity is markedly reduced in the affected brain areas. Nerve growth factor can increase the ChAT activity of brain cholinergic neurons in vitro and in vivo. We have cloned the rat ChAT gene and identified one 5' noncoding exon and 14 exons that account for the entire coding sequence. The exon organization is compared with the protein domains conserved during evolution. These exons are distributed over at least 64 kilobases in the rat genome; the largest intron is at least 14 kilobases long. Within a 0.7 kilobase region immediately upstream of the confirmed sequence of the noncoding exon, TATA-like elements and numerous potential binding sites for transcription factors are found, including AP-1, Sp1, octamer-binding factor(s), CTF/NF-1, and the nuclear oncoprotein Myb. PMID- 1584772 TI - Complete 15N and 1H NMR assignments for the amino-terminal domain of the phage 434 repressor in the urea-unfolded form. AB - The amino-terminal domain of the phage 434 repressor consisting of residues 1-69 forms a globular structure of five tightly packed helices, with nearly identical molecular architectures in crystals and in solution. Upon addition of urea to an aqueous solution of this protein, the NMR spectrum of a second form of the protein appears in addition to the native form, and at a urea concentration of 7 M, this urea-unfolded form is the only species observed. At intermediate urea concentrations, the two forms of the protein inter-convert at a rate that allows the observation of the exchange process by NMR. Starting from the previous assignments for the native protein, we obtained nearly complete sequence-specific (1)H and (15)N NMR assignments for the unfolded form of the protein. For most amino acid residues, the (1)H chemical shifts of the urea-unfolded protein are very similar to the random coil values, but some discrete regions of the polypeptide chain were identified that are likely to retain residual nonrandom spatial structure as evidenced by deviations of (1)H chemical shifts and amide proton exchange rates from the expected random coil values. PMID- 1584773 TI - Crystal structure of an engineered subtilisin inhibitor complexed with bovine trypsin. AB - Proteinase specificity of a proteinaceous inhibitor of subtilisin (SSI; Streptomyces subtilisin inhibitor) can be altered so as to strongly inhibit trypsin simply by replacing P1 methionine with lysine (with or without concomitant change of the P4 residue) through site-directed mutagenesis. Now the crystal structure of one such engineered SSI (P1 methionine converted to lysine and P4 methionine converted to glycine) complexed with bovine trypsin has been solved at 2.6 A resolution and refined to a crystallographic R factor of 0.173. Comparing this structure with the previously established structure of the native SSI complexed with subtilisin BPN', it was found that (i) P1 lysine of the mutant SSI is accommodated in the S1 pocket of trypsin as usual, and (ii) upon complex formation, considerable conformation change occurs to the reactive site loop of the mutant SSI. Thus, in this case, flexibility of the reactive site loop seems important for successfully changing the proteinase specificity through mere replacement of the P1 residue. PMID- 1584774 TI - Demonstration of nuclear compartmentalization of glutathione in hepatocytes. AB - The intracellular distribution of glutathione (GSH) in cultured hepatocytes has been investigated by using the compound monochlorobimane (BmCl), which interacts specifically with GSH to form a highly fluorescent adduct. Image analysis of BmCl labeled hepatocytes predominantly localized the fluorescence in the nucleus; the nuclear/cytoplasmic concentration gradient was approximately three. This concentration gradient was collapsed by treatment of the cells with ATP-depleting agents. The uneven distribution of BmCl fluorescence was not attributable to (i) nonspecific interaction of BmCl with protein sulfhydryl groups, (ii) any selective nuclear localization of the GSH transferase(s) catalyzing formation of the GSH-BmCl conjugate, or (iii) any apparent alterations in cell morphology from culture conditions, suggesting that this distribution did, indeed, reflect a nuclear compartmentalization of GSH. That the nuclear pool of GSH was found more resistant to depletion by several agents than the cytoplasmic pool supports the assumption that GSH is essential in protecting DNA and other nuclear structures from chemical injury. PMID- 1584775 TI - On the structure of the nickel/iron/sulfur center of the carbon monoxide dehydrogenase from Rhodospirillum rubrum: an x-ray absorption spectroscopy study. AB - The nickel/iron/sulfur center of the carbon monoxide dehydrogenase (carbon monoxide:(acceptor)oxidoreductase; EC 1.2.99.2) enzyme from Rhodospirillum rubrum (Rr-CODH) was studied by x-ray absorption spectroscopy at the Ni K edge. Extended x-ray absorption fine structure data show that the first Ni coordination shell consists of 2 S atoms at 2.23 A and 2-3 N/O atoms at 1.87 A. The edge structure indicates a distorted tetrahedral or five-coordinate Ni environment in both oxidized and reduced Rr-CODH. By comparing second-shell extended x-ray absorption fine structure data of Rr-CODH to that of (Et4N)3[NiFe3S4(SEt)4], a cubane-type cluster, it was clearly established that Ni in the Rr-CODH center is not involved in the core of a NiFe3S4 cubane cluster. One model consistent with the results is a mononuclear Ni2+ site, bridged by S-Cys or sulfide to one or both of the Fe4S4 clusters of the enzyme, with the remaining coordination sites occupied by additional S-Cys or N/O-liganding amino acid residues. PMID- 1584776 TI - A gene homologous to chloroplast carbonic anhydrase (icfA) is essential to photosynthetic carbon dioxide fixation by Synechococcus PCC7942. AB - To understand the CO2-concentrating mechanism in cyanobacteria, a genomic DNA fragment that complements a temperature-sensitive high-CO2 (5%)-requiring mutant of Synechococcus PCC7942 has been isolated. An open reading frame (ORF272) encoding a polypeptide of 272 amino acids (Mr, 30,184) was found within the genomic region located 20 kilobases downstream from the genes for ribulose-1,5 bisphosphate carboxylase/oxygenase (rbcLS). Insertion of a kanamycin-resistance gene cartridge within the ORF272 in wild-type cells led to a high-CO2-requiring phenotype. Strains carrying a gene disabled by insertional mutagenesis accumulated inorganic carbon in the cells, but they could not fix it efficiently, even though ribulose-1,5-bisphosphate carboxylase activity was comparable to that of the wild-type strain. Therefore, the ORF272 was designated as a gene icfA, which is essential to inorganic carbon fixation. Furthermore, the predicted icfA gene product shared significant sequence similarities with plant chloroplast carbonic anhydrases (CAs) from pea (22%) and spinach (22%) and also with the Escherichia coli cynT gene product (31%), which was recently identified to be E. coli CA. These results indicate that the putative CA encoded by icfA is essential to photosynthetic carbon dioxide fixation in cyanobacteria and that plant chloroplast CAs may have evolved from a common ancestor of the prokaryotic CAs, which are distinct from mammalian CAs and Chlamydomonas periplasmic CAs. PMID- 1584777 TI - Semisynthetic combinatorial antibody libraries: a chemical solution to the diversity problem. AB - The properties of naivete and large diversity are considered to be essential starting features for combinatorial antibody libraries that eschew immunization by evolution in vitro. We have prepared large libraries with such properties by using random oligonucleotide synthesis, which has the potential to create approximately 10(20) complementarity-determining regions for antibody heavy chains. When combined with light chains and expressed on phage surfaces, high affinity antibodies could be selected from 5.0 x 10(7) Escherichia coli transformants. Remarkably, antibodies selected only for binding displayed both general structural features known to be important in nature's own antibodies and specific consensus sequences thought to be critical for interaction with the hapten against which the library was selected. Semisynthetic and ultimately totally synthetic combinatorial libraries when coupled with mutation and selection procedures should replace immunization for generation of reagent, therapeutic, and catalytic antibodies. PMID- 1584778 TI - Environment affects amino acid preference for secondary structure. AB - Three equivocal amino acid sequences were synthesized that are predicted to be alpha-helical from amino acid preference but are found to be primarily beta strand from x-ray diffraction of their respective proteins. In some solvent systems we recover the alpha-helical structure predicted by amino acid preference, whereas in other systems we mimic the interior of the protein and produce a beta-strand. These results are experimental proof that the environment is important in determining the secondary structure formed by an amino acid sequence; therefore schemes that predict secondary structure from amino acid sequence alone can never be totally successful. PMID- 1584779 TI - Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. AB - We have inactivated the endogenous apolipoprotein E (apoE) gene by using gene targeting in mouse embryonic stem (ES) cells. Two targeting plasmids were used, pJPB63 and pNMC109, both containing a neomycin-resistance gene that replaces a part of the apoE gene and disrupts its structure. ES cell colonies targeted after electroporation with plasmid pJPB63 were identified by the polymerase chain reaction (PCR) followed by genomic Southern analysis. Of 648 G418-resistant colonies analyzed, 9 gave a positive signal after PCR amplification, and 5 of them were confirmed as targeted by Southern blot analysis. The second plasmid, pNMC109, contains the negatively selectable thymidine kinase gene in addition to the neomycin-resistance gene. After electroporation with this plasmid, 177 colonies resistant both to G418 and ganciclovir were analyzed; 39 contained a disrupted apoE gene as determined by Southern blotting. Chimeric mice were generated by blastocyst injection with 6 of the targeted lines. One of the lines gave strong chimeras, three of which transmitted the disrupted apoE gene to their progeny. Mice homozygous for the disrupted gene were produced from the heterozygotes; they appear healthy, even though they have no apolipoprotein E in their plasma. PMID- 1584780 TI - Human growth hormone promotes engraftment of murine or human T cells in severe combined immunodeficient mice. AB - Growth hormone (GH) has previously been implicated in T-cell development, and here we test its efficacy in promoting T-lymphocyte engraftment in mice with severe combined immune deficiency (SCID). SCID mice receiving syngeneic thymocytes and treated with recombinant human GH (rhGH) had significantly better T-cell engraftment in their lymph nodes. Human T-cell engraftment was also strongly promoted by rhGH in SCID recipients receiving human peripheral blood lymphocytes. Additionally, although mature human cells have not been thought to enter the murine thymus, human T cells were detected in the SCID thymus after rhGH treatment. Thus, rhGH can be used to optimize long-term peripheral T-cell engraftment in these human-mouse chimeras and may also be useful clinically in treating T-cell deficiencies. PMID- 1584781 TI - Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. AB - A wild-type p53 gene under control of the metallothionein MT-1 promoter was stably transfected into human colon tumor-derived cell line EB. Repeated inductions of the metallothionein wild-type p53 gene with zinc chloride results in progressive detachment of wild-type p53 cells grown on culture dishes. Examination at both the light and electron microscopic level revealed that cells expressing wild-type p53 developed morphological features of apoptosis. DNA from both attached and detached cells was degraded into a ladder of nucleosomal-sized fragments. Expression of wild-type p53 inhibited colony formation in soft agar and tumor formation in nude mice. Furthermore, established tumors in nude mice underwent regression if wild-type p53 expression was subsequently induced. Regressing tumors showed histological features of apoptosis. Thus, regression of these tumors was the result of apoptosis occurring in vivo. Apoptosis may be a normal part of the terminal differentiation program of colonic epithelial cells. Our results suggest that wild-type p53 could play a critical role in this process. PMID- 1584782 TI - Genetic identification of the DNA binding domain of Escherichia coli LexA protein. AB - Two genetic approaches were taken to define the DNA binding domain of LexA protein, the repressor of the Escherichia coli SOS regulon. First, several dominant negative lexA mutants defective in DNA binding were isolated. The mutations altered amino acids in a region similar to the helix-turn-helix, a DNA binding domain of other repressors and DNA binding proteins. Second, the region encoding the predicted DNA recognition helix was subjected to oligonucleotide directed mutagenesis and mutant LexA proteins with altered or relaxed specificity for several recA operator positions were isolated. By examining the effects of a series of amino acid substitutions on repressor specificity, it was shown that a glutamic acid residue at position 45 in LexA protein is important for recognition of the first base pair (G.C) in the recA operator. PMID- 1584783 TI - Identification of highest-affinity ligands by affinity selection from equimolar peptide mixtures generated by robotic synthesis. AB - A fully automated peptide synthesizer has been constructed that is capable of the simultaneous synthesis of up to 36 individual peptides and the synthesis of equimolar peptide mixtures. The instrument consists of an array of reaction vessels, a series of solenoid valves to control liquid flow, and a Zymark robot to deliver solvents and reagents; all components are computer controlled and coordinated. Equimolar peptide mixtures are obtained by algorithms that automate the mixing and distribution of peptide-resin particles. This technology was used to synthesize a library of 361 peptides, generated by randomizing two critical binding residues of a 10-mer epitope known to bind an anti-human immuno deficiency virus gp120 monoclonal antibody. Each critical residue was substituted with 19 amino acids consisting of all the natural amino acids except cysteine. The library was synthesized as 19 pools, each containing 19 peptides. Each pool was screened in a solution-phase competition ELISA assay. The 12 most inhibitory peptides in the library were isolated by a rapid affinity-selection method and were identified by mass spectrometry and amino acid analysis. The binding properties of these 12 selected peptides were verified by synthesis and assay of the individual peptides. The two critical residues investigated were found to contribute independently to antibody binding. PMID- 1584784 TI - Peptidyl-prolyl cis-trans isomerase improves the efficiency of protein disulfide isomerase as a catalyst of protein folding. AB - The cis-trans isomerization of prolyl peptide bonds and the formation of disulfide bonds are both slow steps in protein folding. By using ribonuclease T1 as a model system, we show that these two processes can become linked in the oxidative folding of reduced proteins and that the formation of the correct disulfide bonds is facilitated in the presence of peptidyl-prolyl cis-trans isomerase. In particular, the efficiency of protein disulfide isomerase (EC 5.3.4.1) as a catalyst of disulfide bond formation in the course of oxidative folding is markedly improved when peptidyl-prolyl cis-trans isomerase is present simultaneously. Possibly, unfolded or partially folded protein chains with correct prolyl isomers are better substrates for catalysis by protein disulfide isomerase. The interdependence of the two enzymatic activities detected during in vitro folding experiments could be of importance for the de novo folding and disulfide bond formation of nascent proteins in the endoplasmic reticulum. PMID- 1584785 TI - Methods for the large-scale synthesis of psoralen furan-side monoadducts and diadducts. AB - We report methods for the preparation of multimicromole quantities of extremely pure uniquely photo-adducted psoralen-DNA furan-side monoadducts and diadducts (cross-links). The methods use high-intensity krypton and argon ion lasers in the photoreactions and HPLC methods to purify the required oligonucleotides containing the photoadducts. With these methods we have synthesized 2-3 mumol of 8-mer psoralen furan-side monoadduct and diadduct. These methods allow one to generate large amounts of psoralenated DNA oligonucleotides and facilitate their study by NMR and x-ray crystallography. PMID- 1584787 TI - Surfactant-induced sealing of electropermeabilized skeletal muscle membranes in vivo. AB - Victims of major electrical trauma frequently suffer extensive skeletal muscle and nerve damage, which is postulated to be principally mediated by electroporation and/or thermally driven cell membrane permeabilization. We have investigated the efficacy of two blood-compatible chemical surfactants for sealing electroporated muscle membranes. In studies using cultured skeletal muscle cells, poloxamer 188 (P188; an 8.4-kDa nonionic surfactant) blocks, and neutral dextran (10.1 kDa) substantially retards, carboxyfluorescein release from electropermeabilized cell membranes. To test whether P188 administered intravenously could have the same therapeutic effect in vivo, the rat biceps femoris muscle flap attached by its arteriovenous pedicle was electropermeabilized until its electrical resistivity dropped to 50% of the initial value. P188 (460 mg/kg) administered intravenously 20 min postshock restored the resistivity to 77% of the initial value. When P188 was administered intravenously 5 min before shock, a dose-dependent impedance recovery rate was observed. Neither neutral dextran (460 mg/kg) nor sterile saline was effective. Histopathologic studies indicated that postshock poloxamer administration reduced tissue inflammation and damage in comparison with dextran-treated or control tissues. Electrophysiologic evidence of membrane damage was not observed in flaps of animals pretreated with poloxamer. These results suggest that it may be possible to seal in vivo tissue membranes injured by electrical, thermal, or other membrane-damaging forces. PMID- 1584786 TI - Production of germ-line chimeras in zebrafish by cell transplants from genetically pigmented to albino embryos. AB - To determine whether embryonic cells transplanted from one zebrafish embryo to another can contribute to the germ line of the recipient, and to determine whether pigmentation can be used as a dominant visible marker to monitor cell transplants, we introduced cells from genetically pigmented (donor) embryos to albino recipients at midblastula stage. By 48 hr many of the resulting chimeras expressed dark pigment in their eyes and bodies, characteristics of donor but not albino embryos. By 4-6 weeks of age pigmentation was observed on the body of 23 of 70 chimeras. In contrast to fully pigmented wild-type fish, pigmentation in chimeras appeared within transverse bands running from dorsal to ventral. Pigmentation patterns differed from one fish to another and in almost every case were different on each side of a single fish. At 2-3 months of age chimeras were mated to albino fish to determine whether pigmented donor cells had contributed to the germ line. Of 28 chimeric fish that have yielded at least 50 offspring each, 5 have given rise to pigmented progeny at frequencies of 1-40%. The donor cells for some chimeras were derived from embryos that, in addition to being pigmented, were transgenic for a lacZ plasmid. Pigmented offspring of some germ line chimeras inherited the transgene, confirming that they descended from transplanted donor cells. Our ability to make germ-line chimeras suggests that it is possible to introduce genetically engineered cells into zebrafish embryos and to identify the offspring of these cells by pigmentation at 2 days of age. PMID- 1584788 TI - Excretion of putrescine by the putrescine-ornithine antiporter encoded by the potE gene of Escherichia coli. AB - Excretion of putrescine from Escherichia coli was assessed by measuring its uptake into inside-out membrane vesicles. The vesicles were prepared from wild type E. coli or E. coli transformed with plasmids containing one of the three polyamine transport systems. The results indicate that excretion of putrescine is catalyzed by the putrescine transport protein, encoded by the potE gene located at 16 min on the E. coli chromosome. Loading of ornithine (or lysine) inside the vesicles was essential for the uptake of putrescine, indicating that the protein exchanges putrescine and ornithine (or lysine) by an antiport mechanism. The Km and Vmax values for the putrescine uptake by inside-out membrane vesicles were 73 microM and 0.82 nmol/min per mg of protein, respectively. The antiport protein (potE protein) also catalyzed putrescine-putrescine and ornithine-ornithine exchange. The transport activity was not disturbed by inhibitors of energy production such as KCN and carbonyl cyanide m-chlorophenylhydrazone. When intact E. coli was used instead of the inside-out membrane vesicles, excretion of putrescine was also catalyzed by the antiport protein in the presence of ornithine in the medium. PMID- 1584789 TI - The Escherichia coli chromosome contains specific, unmethylated dam and dcm sites. AB - The Escherichia coli chromosome encodes two methylases, dam and dcm, which recognize the sequences GATC and CC(A/T)GG, respectively. Specific dam and dcm sites on the E. coli chromosome were found to be unmethylated in vivo by using pulsed-filed gel electrophoresis experiments scanning megabase regions of DNA. Some sites were totally unmethylated. The dam sites display variable methylation depending on the local sequence, and, in general, their methylation shows complex modulation by growth conditions and growth rate, suggesting multiple protection mechanisms. Sites resistant to complete dam or dcm methylation appear to be distributed throughout the chromosome. These unusual sites may identify regions of the chromosome with interesting biological functions. PMID- 1584791 TI - Modulation of the RNA-binding activity of a regulatory protein by iron in vitro: switching between enzymatic and genetic function? AB - The iron-responsive element-binding protein (IRE-BP) is an RNA-binding protein that regulates the expression of several mRNAs in response to availability of cellular iron. The iron-dependent control of IRE-BP activity has been reconstituted in vitro. Incubation of purified IRE-BP with iron salts in the presence of the reducing agent cysteine decreases IRE-BP binding to the cognate RNA element. The specificity of this effect is established by several parameters: (i) the interaction of the spliceosomal protein U1A with its U1 small nuclear RNA target sequence as an internal control is unaffected by iron perturbations, (ii) non-iron metals fail to mimic the iron effect, and (iii) iron chelator activates the IRE-binding activity of IRE-BP and titrates the effect of iron salts. Modulation of IRE-BP activity by chelatable iron is reversible and thus does not involve permanent alterations of the integrity of the protein. These findings accurately mirror the physiological basis for iron regulation of transferrin receptor mRNA stability as well as ferritin and erythroid 5-aminolevulinate synthase mRNA translation in vivo. We discuss these data vis-a-vis the structural homology of IRE-BP with the iron-sulfur protein aconitase and propose a mechanism by which the same cytoplasmic protein serves a dual function as an RNA-binding factor and an enzyme. PMID- 1584790 TI - Modification of histidine residues in proteins by reaction with 4-hydroxynonenal. AB - We find that histidine residues in proteins are major targets for reaction with the lipid peroxidation product 4-hydroxynon-2-enal (HNE). Reaction of insulin (which contains no sulfhydryl groups) with HNE leads to the generation of HNE protein adducts, which are converted to radioactive derivatives upon subsequent treatment with NaB[3H]H4. Amino acid analysis of the modified protein showed that the HNE treatment leads to the selective loss of histidine residues and the stiochiometric formation of 3H-labeled amino acid derivatives. The same labeled products were detected in acid hydrolysates of polyhistidine and N acetylhistidine after their reactions with HNE and NaB[3H]H4. The reaction of N acetylhistidine with HNE led to the production of two compounds. Upon acid hydrolysis, both derivatives yielded stoichiometric amounts of histidine. However, after reduction with NaBH4, acid hydrolysis led to a mixture of amino acid derivatives [presumably, isomeric forms of N pi (N tau)-1,4 dihydroxynonanylhistidine] that were indistinguishable from those obtained from insulin and polyhistidine after similar treatment. Although other possibilities are not excluded, it is suggested that the modification of histidine residues in proteins by HNE involves a Michael-type addition of the imidazole nitrogen atom of histidine to the alpha, beta-unsaturated bond of HNE, followed by secondary reaction involving the aldehyde group with the C-4 hydroxyl group of HNE. The reaction of histidine residues with HNE provides the basis for methods by which the contributions of HNE in the modification of proteins can be determined. PMID- 1584792 TI - Molecular cloning of epididymal and seminal vesicular transcripts encoding a semenogelin-related protein. AB - Freshly ejaculated human semen has the appearance of a loose gel in which the predominant structural protein components are the seminal vesicle-secreted semenogelins (Sg). The primary structure of the 439-residue SgI has previously been obtained by cDNA cloning. This cDNA cross-hybridizes to a larger transcript coding for a second secretory protein, SgII. Here we report the almost complete structure of a precursor of SgII established by lambda gt11 clones isolated from epididymal and seminal vesicular cDNA libraries. The deduced amino acid sequence of the 559-residue mature protein has a molecular weight of 62,931 but an increase in weight may be provided by asparagine-linked oligosaccharide attachment at residue 249. SgII, which has 78% overall identity with SgI, contains eight 60-residue regions that display conspicuous internal sequence similarity, whereas SgI only contains six of these regions. The SgII structure is translated from an open reading frame in a polyadenylylated 2.4-kilobase transcript. The message is abundant in the seminal vesicles but rare in the epididymis. PMID- 1584793 TI - Id gene expression and its suppression by 1,25-dihydroxyvitamin D3 in rat osteoblastic osteosarcoma cells. AB - Id is one of the helix-loop-helix family of proteins that regulate differentiation in several types of cells, including myoblasts. We found that Id mRNA was constitutively expressed in ROS17/2.8 rat osteoblastic osteosarcoma cells and that the level of Id message in these cells was suppressed by 1,25 dihydroxyvitamin D3 (vitamin D), a calcitropic hormone known to enhance expression of differentiation-related phenotypes in these cells. The vitamin D suppression was dose-dependent, starting at 10(-11) M and saturating at 10(-8) M. This vitamin D effect was seen within 6 hr after the initiation of the treatment and lasted at least 48 hr. Cycloheximide did not block the vitamin D suppression of Id message level. Vitamin D reduced the rate of Id gene transcription by approximately 80% as estimated by nuclear run-on assay. Electrophoretic mobility shift assay indicated the specific binding of nuclear factors from ROS17/2.8 cells to an E-box DNA sequence, and the binding signal was enhanced in nuclear extracts of the cells treated with vitamin D. The suppressive effect was specific to vitamin D, since another calcitropic hormone, the synthetic compound dexamethasone, did not suppress Id message expression. These observations indicate the presence of helix-loop-helix proteins in osteoblastic cells and indicate that vitamin D, a potent regulator of differentiation in several types of cells, controls the expression of the helix-loop-helix molecules. PMID- 1584794 TI - Sequence organization of the Balbiani ring 2.1 gene in Chironomus tentans. AB - Balbiani rings are giant chromosomal puffs, containing related genes that provide unique possibilities for in vivo analysis of gene expression at the chromatin and ribonucleoprotein levels. Here, the 5' end of the Balbiani ring 2.1 gene in the dipteran Chironomus tentans has been isolated and the sequence organization of the entire Balbiani ring gene is presented. The gene contains five exons, one being extremely small, only 6 base pairs, and one being extremely large, approximately 30 kilobase pairs. Three introns are located at the 5' end and a fourth one is located at the 3' end. The central 30-kilobase-pair exon is entirely built from tandemly organized repeats. All repeats are virtually identical except for a few variant repeats at both ends of the repeat array. The number of repeats may vary between alleles and the length of the gene therefore changes between 30 and 35 kilobase pairs. PMID- 1584795 TI - Evolution of the vasopressin/oxytocin superfamily: characterization of a cDNA encoding a vasopressin-related precursor, preproconopressin, from the mollusc Lymnaea stagnalis. AB - Although the nonapeptide hormones vasopressin, oxytocin, and related peptides from vertebrates and some nonapeptides from invertebrates share similarities in amino acid sequence, their evolutionary relationships are not clear. To investigate this issue, we cloned a cDNA encoding a vasopressin-related peptide, Lys-conopressin, produced in the central nervous system of the gastropod mollusc Lymnaea stagnalis. The predicted preproconopressin has the overall architecture of vertebrate preprovasopressin, with a signal peptide, Lys-conopressin, that is flanked at the C terminus by an amidation signal and a pair of basic residues, followed by a neurophysin domain. The Lymnaea neurophysin and the vertebrate neurophysins share high sequence identity, which includes the conservation of all 14 cysteine residues. In addition, the Lymnaea neurophysin possesses unique structural characteristics. It contains a putative N-linked glycosylation site at a position in the vertebrate neurophysins where a strictly conserved tyrosine residue, which plays an essential role in binding of the nonapeptide hormones, is found. The C-terminal copeptin homologous extension of the Lymnaea neurophysin has low sequence identity with the vertebrate counterparts and is probably not cleaved from the prohormone, as are the mammalian copeptins. The conopressin gene is expressed in only a few neurons in both pedal ganglia of the central nervous system. The conopressin transcript is present in two sizes, due to alternative use of polyadenylylation signals. The data presented here demonstrate that the typical organization of the prohormones of the vasopressin/oxytocin superfamily must have been present in the common ancestors of vertebrates and invertebrates. PMID- 1584796 TI - Integration of gene maps: chromosome 1. AB - A composite map of 177 loci has been constructed in two steps. The first combined pairwise logarithm-of-odds scores on 127 loci into a comprehensive genetic map. Then this map was projected onto the physical map through cytogenetic assignments, and the small amount of physical data was interpolated for an additional 50 loci each of which had been assigned to an interval of less than 10 megabases. The resulting composite map is on the physical scale with a resolution of 1.5 megabases. In the future these methods may be used to incorporate locations from linkage, contigs, radiation hybrids, restriction fragments, and somatic cell maps. Dense, reliable, and well-documented maps are essential for long-range sequencing and to localize and clone disease genes. PMID- 1584797 TI - Cleavage behavior of calicheamicin gamma 1 and calicheamicin T. AB - Calicheamicin gamma 1 is a potent antitumor antibiotic that cleaves DNA with a high degree of specificity; there is much interest in the recognition process. We have investigated the DNA-cleaving properties of calicheamicin T, a truncated derivative of calicheamicin. We show that calicheamicin T cleaves DNA in a double stranded fashion, indicating that the first two sugars are sufficient to facilitate binding of the aglycone in the minor groove. However, calicheamicin T cleaves DNA nonselectivity. This result suggests that cyclization kinetics do not determine the cleavage specificity of the intact drug. Instead, cleavage specificity probably reflects binding specificity. Because of the recognition sites reported in the original cleavage paper, calicheamicin has been assumed to recognize oligopyrimidine DNA sequences containing G-C base pairs. We show here that calicheamicin also cuts efficiently at A.T tracts, sometimes in preference to G.C-rich homopyrimidine tracts. Crystallographic data and experiments with chemical probes indicate that DNA sequences including G.C base pairs have significantly different local conformations from DNA sequences containing several (four or more) sequential A.T base pairs. This difference makes it unlikely that calicheamicin simply senses inherent groove conformation and suggests that there is some degree of "induced fit." The ability to recognize both A.T- and G.C-rich oligopyrimidine sequences with a high degree of specificity makes calicheamicin an unusual minor-groove binder. PMID- 1584798 TI - Endoproteolytic processing of a farnesylated peptide in vitro. AB - Numerous eukaryotic proteins containing a carboxyl-terminal CAAX motif (C, cysteine; A, aliphatic amino acid; X, any amino acid) require a three-step posttranslational processing for localization and function. The a mating factor of Saccharomyces cerevisiae is one such protein, requiring cysteine farnesylation, proteolysis of the terminal three amino acids, and carboxyl methylation for biological activity. We have used farnesylated a-factor peptides to examine the proteolytic step in the maturation of CAAX-containing proteins. Three distinct carboxyl-terminal protease activities were found in yeast cell extracts that could remove the terminal three residues of a-factor. Two of the proteolytic activities were in cytosolic fractions. One of these activities was a PEP4-dependent carboxypeptidase that was sensitive to phenylmethylsulfonyl fluoride. The other cytosolic activity was PEP4-independent, sensitive to 1,10 phenanthroline, and effectively inhibited by an unfarnesylated a-factor peptide. In contrast, a protease activity in membrane fractions was unaffected by phenylmethylsulfonyl fluoride, 1,10-phenanthroline, or unfarnesylated a-factor peptide. Incubation of membrane preparations from either yeast or rat liver with a radiolabeled farnesylated a-factor peptide released the terminal three amino acids intact as a tripeptide, indicating that this reaction occurred by an endoproteolytic mechanism and that the enzyme most likely possesses a broad substrate specificity. The yeast endoprotease was not significantly affected by a panel of protease inhibitors, suggesting that the enzyme is novel. Zinc ion was shown to inhibit the endoprotease (Ki less than 100 microM). The specific activities of the a-factor carboxyl-terminal membrane endoprotease and methyltransferase clearly indicated that the proteolytic reaction was not rate limiting in these processing reactions in vitro. PMID- 1584799 TI - Mutational spectrometry: a general approach for hot-spot point mutations in selectable genes. AB - To observe point mutational spectra with a high degree of precision, independent large cultures of human lymphoblastoid cells were treated with a mutagen, benzo[a]pyrene diol epoxide, and mutants at the HPRT gene were selected en masse by 6-thioguanine resistance. An average of 1.6 x 10(4) 6-thioguanine-resistant mutants were created per experiment and the kinds, positions, and numbers of the most frequent mutations were examined in exon 3 of the HPRT gene by using a high fidelity polymerase chain reaction and denaturing gradient gel electrophoresis. Sixteen exon 3-specific mutations were found to be predominantly G----T transversions and corresponded to an average of 3500 induced mutants per experiment. Of these mutations, 6 occurred within a run of 6 guanines and 5 occurred in the sequence 5'-GAAGAG-3'. The variation among independent experiments is consistent with the numerical expectation that all 16 mutations fulfill reasonable statistical criteria for mutational hot spots. The agreement with data from various systems using clone-by-clone analysis shows that the protocol reported herein can be a useful tool to study hot-spot point mutational spectra for DNA sequences for which phenotypic selection systems exist. PMID- 1584800 TI - Polar zipper sequence in the high-affinity hemoglobin of Ascaris suum: amino acid sequence and structural interpretation. AB - The extracellular hemoglobin of Ascaris has an extremely high oxygen affinity (P50 = 0.004 mmHg). It consists of eight identical subunits of molecular weight 40,600. Their sequence, determined by protein chemistry, shows two tandemly linked globin-like sequences and an 18-residue C-terminal extension. Two N-linked glycosylation sites contain equal ratios of mannose/glucosamine/fucose of 3:2:1. Electron micrographs suggest that the eight subunits form a polyhedron of point symmetry D4, or 42. The C-terminal extension contains a repeat of the sequence Glu-Glu-His-Lys, which would form a pattern of alternate glutamate and histidine side chains on one side and of glutamate and lysine side chains on the other side of a beta strand. We propose that this represents a polar zipper sequence and that the C-terminal extensions are joined in an eight-stranded beta barrel at the center of the molecule, with histidine and glutamate side chains inside and lysine and glutamate side chains outside the barrel compensating each other's charges. The amino acid sequence of Ascaris hemoglobin fails to explain its high oxygen affinity. PMID- 1584801 TI - Coupling of dual signaling pathways: epidermal growth factor action involves the estrogen receptor. AB - Epidermal growth factor (EGF) reproduces many of the effects of estrogen on the murine female reproductive tract and may partially mediate estrogen-induced growth and differentiation. This study was performed to investigate the mechanism by which EGF elicits estrogen-like actions in the whole animal. EGF was administered to adult ovariectomized mice by slow release pellets implanted under the kidney capsule. The induction of uterine DNA synthesis and phosphatidylinositol lipid turnover by EGF or administration of diethylstilbestrol (5 micrograms/kg), a potent estrogen, was attenuated by the estrogen receptor antagonist ICI 164,384. Furthermore, EGF mimicked the effects of estrogen on enhanced nuclear localization of the estrogen receptor and the formation of a unique form of the estrogen receptor found exclusively in the nucleus. These results suggest that EGF may induce effects similar to those of estrogen in the mouse uterus by an interaction between the EGF signaling pathway and the classical estrogen receptor. The demonstration of cross-talk between polypeptide growth factors and steroid hormone receptors may be of importance to our understanding of the regulation of normal growth and differentiation as well as the mechanisms of transmission of extracellular mitogen signals to the nucleus. PMID- 1584802 TI - Dodeca satellite: a conserved G+C-rich satellite from the centromeric heterochromatin of Drosophila melanogaster. AB - To identify sequences from the centromeric region, we have constructed a Drosophila melanogaster yeast artificial chromosome (YAC) library and screened it with purified DNA from the minichromosome Dp(1;f)1187 derived from the X chromosome. We describe the structure of one clone isolated in this way. This YAC is structurally unstable and contains tandemly repeated G+C-rich 11-mer and 12 mer units, which we call dodeca satellite. Most of this satellite is located near the centromere of an autosome. Cross-hybridizing sequences are found in the genomes of organisms as distant as Arabidopsis thaliana and Homo sapiens. PMID- 1584803 TI - Thymosin beta 4 (Fx peptide) is a potent regulator of actin polymerization in living cells. AB - Thymosin beta 4 (beta 4) is a 5-kDa polypeptide originally identified in calf thymus. Although numerous activities have been attributed to beta 4, its physiological role remains elusive. Recently, beta 4 was found to bind actin in human platelet extracts and to inhibit actin polymerization in vitro, raising the possibility that it may be a physiological regulator of actin assembly. To examine this potential function, we have increased the cellular beta 4 concentration by microinjecting synthetic beta 4 into living epithelial cells and fibroblasts. The injection induced a diminution of stress fibers and a dose dependent depolymerization of actin filaments as indicated by quantitative image analysis of phalloidin binding. Our results show that beta 4 is a potent regulator of actin assembly in living cells. PMID- 1584804 TI - Expression of interleukin 1-inducible genes and production of interleukin 1 by aging human fibroblasts. AB - The interleukin 1 (IL-1)-inducible mRNAs for plasminogen activator inhibitor type 2, manganese superoxide dismutase, and urokinase are overexpressed in old (greater than 70% of life-span completed) but not in young (less than 40% of life span completed) human foreskin fibroblasts. Furthermore, the activity of this superoxide dismutase is greater in old than in young fibroblasts. IL-1 beta mRNA is detected by Northern blot analysis in old fibroblasts and its expression is further enhanced by a treatment with IL-1 alpha. IL-1 alpha and IL-1 beta mRNAs are detected in old foreskin and lung fibroblasts by a sensitive reverse transcription-PCR assay. IL-1 mRNA is consistently expressed after fibroblasts have completed 85% of their in vitro life-span; an assay with specific antibodies shows that IL-1 alpha is present in these fibroblasts. Prolonged treatment with IL-1 receptor antagonist decreases the levels of IL-1 alpha and of IL-1 alpha and IL-1 beta mRNAs. This observation suggests that IL-1 receptor antagonist inhibits an autocrine loop responsible for IL-1 expression. IL-1 mRNA accumulates in young fibroblasts treated with cycloheximide, suggesting that it is transcribed but unstable in these cells; accumulation of IL-1 mRNA in old fibroblasts may be due at least in part to increased stability. IL-1 alpha stimulates DNA synthesis in young fibroblasts but has progressively less effect as the cells age in culture. These data indicate that IL-1 is "constitutively" produced by aging fibroblasts and that IL-1 induces the expression of specific proteins in these cells. The mechanism for this constitutive production of IL-1 is explored in this paper. PMID- 1584806 TI - Primary structure and expression of a gamete lytic enzyme in Chlamydomonas reinhardtii: similarity of functional domains to matrix metalloproteases. AB - A gamete lytic enzyme (GLE) of Chlamydomonas reinhardtii is a zinc metalloprotease and mediates digestion of the cell walls of the two mating-type gametes during mating as a necessary prelude to cell fusion. The nucleotide sequence analysis of a cDNA revealed that GLE is synthesized in a preproenzyme form, a 638-amino acid polypeptide (Mr, 69,824) with a 28-amino acid signal peptide, a 155-amino acid propolypeptide, and a 455-amino acid mature polypeptide (Mr, 49,633). A potential site for autocatalytic activation was contained within the propolypeptide and a zinc binding site found within the mature polypeptide; both sites were highly homologous to those in mammalian collagenase. A putative calcium binding site was present in the near C-terminal region of the mature GLE. Both propolypeptide and mature polypeptide had potential sites for asparagine linked glycosylation, and the Arg-(Pro)3 and Arg-(Pro)2 motifs, which are known to exist in hydroxyproline-rich glycoproteins of the Chlamydomonas cell wall. Northern blot analysis revealed that steady-state levels of the 2.4-kilobase GLE mRNA increased during growth and mitotic cell division in the vegetative cell cycle and also increased markedly during gametogenesis under nitrogen-starved conditions. PMID- 1584805 TI - 1 alpha,25-dihydroxyvitamin D3 regulates the transcription of carbonic anhydrase II mRNA in avian myelomonocytes. AB - Carbonic anhydrase II (CAII) is highly expressed in the osteoclast, where it is involved in the process of extracellular acidification required for bone resorption. We have previously shown that 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], a steroid hormone that regulates the differentiation of macrophages and osteoclasts, induces the expression of CAII mRNA and protein in avian bone marrow cells. To determine whether this regulation occurred at the gene level, we have studied the effects of 1,25(OH)2D3 on CAII expression in a transformed myelomonocytic avian cell line (BM2). As observed in nontransformed cells, 1,25(OH)2D3 markedly increased CAII biosynthesis and mRNA levels. The increase in CAII mRNA was detected as early as 3 hr after adding the hormone (1.9 fold) and reached 4.7-fold by 48 hr. These effects were completely blocked by actinomycin D, and nuclear run-on analysis confirmed that 1,25(OH)2D3 increased the rate of CAII gene transcription. In contrast, induction of CAII mRNA expression was not affected by inhibition of protein synthesis with cycloheximide, and no significant changes in mRNA stability were seen. Thus, 1,25(OH)2D3 modulates CAII gene expression at the transcriptional level, and this effect does not require de novo synthesis of other gene products. These results suggest that activation of the CAII gene occurs early in the differentiation events triggered by vitamin D3 in myelomonocytic cells. PMID- 1584807 TI - Quantitation of reversible binding by particle counting: hapten-antibody interaction as a model system. AB - With a view toward developing a general method for measuring intrinsic equilibrium constants for the reversible interactions between two ligands, we used an antibody-hapten model system [2,4-dinitrophenyl (DNP) hapten and anti-DNP antibody] to explore an approach based on particle counting of uniform polystyrene spheres to which the hapten is coupled covalently. This approach was made possible by an optical pulse particle size analyzer that accurately counts individual sphere clusters and quantitates with high precision specific aggregation of spheres crosslinked by antibody. The reduction in crosslinking that results from competition for antibody binding sites between a soluble DNP ligand and immobilized DNP groups on the spheres provides the basis for measuring the intrinsic equilibrium constant for the soluble ligand-antibody interaction. The binding constants measured in this way for several DNP ligands and an anti DNP antibody (2A1) agreed with the values obtained by conventional methods. The range of intrinsic equilibrium constants that can be determined by particle counting is likely to be exceptionally wide and a value as low as 10(3) liters/mol has been measured. And since all soluble antigens, regardless of their mass, acquire the same ability to scatter light as a result of their immobilization on the much larger uniform spheres (0.36 microns), the approach described here should be applicable to virtually any molecularly dispersed antigen and its monoclonal antibody. PMID- 1584808 TI - Embryonic development period and the prevalence of avian blood parasites. AB - Variation in prevalence of avian hematozoa is related to taxonomic affiliation at the level of the family or subfamily but not of the genus within families. Prevalence is comparatively insensitive to the influences of habitat and season; however, temperate species have higher incidences of infection than tropical species belonging to the same families. Among taxa of nonraptorial altricial landbirds, hematozoan prevalence is inversely related to the length of the incubation period but shows little relationship to body size and rate of postnatal development. This finding suggests a possible link between the duration of embryonic development and the ability to resist or control infection, possibly due to maturational processes in the avian immune system. PMID- 1584809 TI - Mutations in the catalytic subunit of cAMP-dependent protein kinase result in unregulated biological activity. AB - Mutations were identified in the catalytic subunit (C) of the cAMP-dependent protein kinase (EC 2.7.1.37) that block inactivation by regulatory subunit (R) without compromising catalytic activity. Randomly mutagenized mouse C expression vectors were screened functionally for clones that stimulated gene induction in the presence of excess R. Point mutations in the C coding sequence were identified that result in a His----Gln substitution at amino acid 87 (His87Gln) and a Trp----Arg change at amino acid 196 (Trp196Arg). In contrast to wild-type C, both mutants retained partial activity in the presence of excess R isoform RI alpha, although only Trp196Arg retained partial activity in the presence of excess R isoform RII alpha. A C expression vector that included both mutations was fully active in promoting gene induction and was virtually unaffected by an 80-fold excess of either RI alpha or RII alpha. These results demonstrate that mutations at His-87 and Trp-196 alter R interactions with C at a site that is not involved in substrate recognition or enzymatic activity. In contrast to these randomly generated mutations, a site-specific alteration of the autophosphorylated Thr-197 to an Ala resulted in an 80% loss of biological activity and partial resistance to R inhibition. The location and proximity of His-87 and Trp-196 in the crystal structure of C suggest a surface domain that may interact with a region of R that is outside of the substrate/pseudosubstrate site. PMID- 1584810 TI - Observing the 1H NMR signal of the myoglobin Val-E11 in myocardium: an index of cellular oxygenation. AB - The 1H NMR signal from oxymyoglobin, a low-concentration diamagnetic protein, is visible in myocardial tissue. The methyl group of the Val-E11 resonates in a clear spectral region at -2.76 ppm and responds to dynamic changes in cellular oxygenation. With CO, the signal shifts to -2.4 ppm. The Val-E11 peak assignment and its response to oxygen and CO agree perfectly with previous myoglobin solution studies. Intracellular oxygen level can now be determined in vivo with the signal intensity ratio of oxymyoglobin/deoxymyoglobin, reflected by the Val E11 and His-F8 peaks in the 1H NMR spectra. Moreover, protein structure-function relationship in vivo can now be probed. PMID- 1584811 TI - Endoplasmic reticulum resident protein of 90 kilodaltons associates with the T- and B-cell antigen receptors and major histocompatibility complex antigens during their assembly. AB - In the endoplasmic reticulum (ER), newly synthesized subunits of the T-cell antigen receptor (TCR), membrane-bound immunoglobulin (mIg), and major histocompatibility complex (MHC) class I antigens must fold correctly and assemble completely into multimeric protein complexes prior to transport to the cell surface. Although folding and assembly may occur spontaneously, the concept that molecular chaperones facilitate these events is emerging. Here, an intracellular protein of 90-kDa apparent molecular mass, denoted IP90, was shown to be an ER resident protein that associated with partial complexes of the TCR, mIg, and MHC class I proteins but was absent from fully assembled complexes. We speculate that IP90 might participate in folding and assembly processes of these and other multisubunit protein complexes during their transit through the ER. PMID- 1584813 TI - Mechanism of human methyl-directed DNA methyltransferase and the fidelity of cytosine methylation. AB - The properties of the methyl-directed DNA (cytosine-5-)-methyltransferase (EC 2.1.1.37) suggest that it is the enzyme that maintains patterns of methylation in the human genome. Proposals for the enzyme's mechanism of action suggest that 5 methyldeoxycytidine is produced from deoxycytidine via a dihydrocytosine intermediate. We have used an oligodeoxynucleotide containing 5 fluorodeoxycytidine as a suicide substrate to capture the enzyme and the dihydrocytosine intermediate. Gel retardation experiments demonstrate the formation of the expected covalent complex between duplex DNA containing 5 fluorodeoxycytidine and the human enzyme. Formation of the complex was dependent upon the presence of the methyl donor S-adenosylmethionine, suggesting that it comprises an enzyme-linked 5-substituted dihydrocytosine moiety in DNA. Dihydrocytosine derivatives are extremely labile toward hydrolytic deamination in aqueous solution. Because C-to-T transition mutations are especially prevalent at CG sites in human DNA, we have used high-performance liquid chromatography to search for thymidine that might be generated by hydrolysis during the methyl transfer reaction. Despite the potential for deamination inherent in the formation of the intermediate, the methyltransferase did not produce detectable amounts of thymidine. The data suggest that the ability of the human methyltransferase to preserve genetic information when copying a methylation pattern (i.e., its fidelity) is comparable to the ability of a mammalian DNA polymerase to preserve genetic information when copying a DNA sequence. Thus the high frequency of C-to-T transitions at CG sites in human DNA does not appear to be due to the normal enzymatic maintenance of methylation patterns. PMID- 1584812 TI - Neural-specific expression, genomic structure, and chromosomal localization of the gene encoding the zinc-finger transcription factor NGFI-C. AB - The nerve growth factor-induced clone C (NGFI-C) gene encodes a zinc-finger transcription factor that is rapidly induced by nerve growth factor in rat pheochromocytoma PC12 cells and by seizure in brain. NGFI-C is closely related to the previously described early response genes, nerve growth factor-induced clone A (NGFI-A or EGR1), EGR2, and EGR3. These four early response (immediate early) proteins all contain very similar zinc-finger DNA binding domains; in addition, analysis of the non-zinc-finger region revealed that they share an additional five highly homologous subdomains, four of which are within the amino terminus. The 5' flanking region of NGFI-C contains several cAMP response elements but does not contain any serum-response elements or CArG boxes [CC(A/T)6GG], cis-acting elements commonly involved in early response gene regulation. NGFI-C mRNA was detected in neural tissues of postnatal animals, but no expression was found in rat embryos. In situ hybridization demonstrated that NGFI-C is rapidly induced in the dentate gyrus of the hippocampus after seizure, but in contrast to NGFI-A, increases in NGFI-C mRNA were not detected in the overlying cortex. By using fluorescence in situ hybridization, NGFI-C was localized to human chromosome 2p13. This region contains a constitutive fragile site that is associated with chromosomal breakpoints and translocations characteristic of some chronic lymphocytic leukemias. PMID- 1584814 TI - Proteins on exocytic vesicles mediate calcium-triggered fusion. AB - In many exocytic systems, micromolar concentrations of intracellular Ca2+ trigger fusion. We find that aggregates of secretory granules isolated from sea urchin eggs fuse together when perfused with greater than or equal to 10 microM free Ca2+. Mixing of membrane components was demonstrated by transfer of fluorescent lipophilic dye, and melding of granule contents was seen with differential interference microscopy. A technique based upon light scattering was developed to conveniently detect fusion. Two protein modifiers, trypsin and N-ethylmaleimide, inhibit granule-granule fusion at concentrations similar to those that inhibit granule-plasma membrane fusion. We suggest that molecular machinery sufficient for Ca(2+)-triggered fusion resides on secretory granules as purified and that at least some of these essential components are proteinaceous. PMID- 1584816 TI - Oscillations in the insect brain: do they correspond to the cortical gamma-waves of vertebrates? AB - gamma-waves, relatively high-frequency oscillations (30-80 Hz) that can be recorded in the olfactory system and the visual cortex of vertebrates, have recently attracted much attention. A role as an information carrier is under discussion, a possible involvement in "feature linking" has been suggested, and they have also been implicated functionally in phenomena such as mind consciousness or awareness. It has long been known that stimulus-dependent high frequency oscillations (hf waves) can also be recorded from the optic lobes of arthropods. These oscillations in flies have been examined and found to be analogous to the gamma-waves in many respects. Based on knowledge of the anatomy and physiology of the visual system in flies, the most plausible interpretation of the function of these oscillations differs from the interpretations of the vertebrate gamma-waves currently under consideration. PMID- 1584815 TI - Characterization of a single-chain T-cell receptor expressed in Escherichia coli. AB - Despite progress in defining the nature of major histocompatibility complex products that are recognized by the T-cell antigen receptor, the binding properties and structure of the receptor have not been solved. The primary problem has been the difficulty in obtaining sufficient quantities of active receptor. In this report we show that a single-chain T-cell receptor gene can be expressed in Escherichia coli. The protein consists of the variable (V) regions of the alpha and beta chains (V alpha and V beta) encoded by the cytotoxic T lymphocyte clone 2C (a H-2b anti-H-2d alloreactive cell line) linked by a 25 amino acid flexible peptide. Solubilized extracts that contain the 27-kDa V alpha 3V beta 8 protein are positive in solid-phase immunoassays with the anti-V beta 8 antibody KJ16 and the anti-clonotypic antibody 1B2. Approximately 1% of the protein can be specifically purified on a 1B2-conjugated column. These results indicate that a fraction of the protein is able to fold into a native conformation and that single-chain proteins should be useful not only as immunogens for eliciting anti-T-cell receptor antibodies but in the study of T cell receptor structure and function. PMID- 1584817 TI - Professional file. PMID- 1584819 TI - A teaching role that benefits all. Developing teaching skills in clinical nurses. PMID- 1584818 TI - Creating happy families. The effects of adoption on those involved. PMID- 1584820 TI - Skills that can increase your autonomy. Management skills for clinical nurses. PMID- 1584821 TI - A safe environment for care. Infection control nurses' role in mental health units. PMID- 1584822 TI - A chance to overcome the odds. Nursing care of patients administered interleukin 2. PMID- 1584823 TI - A systematic approach can reduce side-effects. A protocol for pain relief in neonates. PMID- 1584824 TI - In training for motherhood? Effects of exercise for pregnant women. PMID- 1584825 TI - Helping children adjust to parental epilepsy. PMID- 1584826 TI - A lifeline offering support. Nurses' role in fertility counselling. PMID- 1584827 TI - How do you make your treatment decision? PMID- 1584828 TI - When anything is good enough. PMID- 1584829 TI - Schedule dependence of the interaction of naloxone and chlordiazepoxide. AB - Reports that the opiate antagonist, naloxone, blocks the anticonflict effects of diazepam and chlordiazepoxide suggest endogenous opioid involvement in the anxiolytic actions of the benzodiazepines. However, naloxone's ability to antagonize the anticonflict effects of the benzodiazepines is not universal, but schedule specific. The present experiments investigated the importance of the timing of conflict periods and control of reinforcement on the naloxone benzodiazepine interaction. We tested the effects of naloxone (3 mg/kg, IP) and chlordiazepoxide (5 mg/kg, IP) on acquisition of a successive discrimination schedule, with nonreward periods similar in length and frequency to those of signalled DRL, and on an FI60-s schedule. Chlordiazepoxide increased rewarded responding and, unexpectedly, decreased nonrewarded responding during acquisition of successive discrimination. This reduction in nonrewarded responding was reversed by naloxone. Under the FI60 schedule, chlordiazepoxide increased nonrewarded responding, an effect that was totally blocked by naloxone at the beginning of the FI. Naloxone's ability to reverse the response-releasing effect of chlordiazepoxide decreased later in the FI. These results suggest endogenous opioid systems are involved in the anxiolytic actions of the benzodiazepines when the animal is adapting to recently introduced conflict. Once adaptation occurs, other neurotransmitter systems mediate the actions of the benzodiazepines. PMID- 1584830 TI - Modelling drug kinetics with brain stimulation: dopamine antagonists increase self-stimulation. AB - The rewarding effects of brain stimulation and drugs are believed to depend on a common neural system. However, the pattern of responding produced by drug reinforcers is different from the pattern produced by conventional brain stimulation. Furthermore, pharmacological antagonists of reinforcement increase the rate of drug self-administration but depress self-stimulation. To test the hypothesis that the differences in the characteristics of brain stimulation and drugs as reinforcers are due to differences in the kinetics of drugs and brain stimulation, we modelled drug kinetics with frequency-modulated trains of brain stimulation. We report that animals will self-administer such brain stimulation in a manner that resembles drug self-administration and that, under these conditions, dopamine antagonists can increase the rate of self-stimulation. PMID- 1584831 TI - Repeated administration of low doses of cocaine enhances the sensitivity of 5-HT2 receptor function. AB - The acute and chronic effects of cocaine were evaluated on the 5 hydroxytryptamine (5-HT)-receptor 5-HT2 mediated behavioral function, the head twitch response (HTR), in mice. In a recent study, we reported that the (+/-)-1 (2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI)-induced HTR was dose dependently reduced by cocaine via indirect stimulation of serotonergic 5-HT1A and adrenergic alpha 2 receptors. In the present investigation, the HTR was evoked by the nonselective 5-HT agonist 5-methoxy-N,N-dimethyltryptamine hydrogen oxolate (5-MeO-DMT). Cocaine by itself failed to produce HTR but dose dependently inhibited the 5-MeO-DMT-induced behavior. Cocaine's effects were not due to 5-HT3 antagonism since acute administration of the more potent 5-HT3 antagonist (ICS 205,930) failed to produce or modify the 5-MeO-DMT-induced behavior. During withdrawal from chronic cocaine treatment (5-20 mg/kg), 5-MeO-DMT-induced HTR was enhanced. Depending upon the cocaine dose used, the induced supersensitivity persisted up to 172 h following cessation of cocaine treatment. The mechanisms of cocaine-induced supersensitivity were further investigated using the more selective 5-HT2 agonist DOI. Withdrawal from a low-dose (0.03-1.25 mg/kg) chronic cocaine treatment caused the DOI-induced HTR to increase, whereas withdrawal from a 5- and 10-mg/kg cocaine regimen had no significant effect. The maximal effect persisted up to 36 h following termination of cocaine treatment. Relative to vehicle-exposed controls, withdrawal from cocaine treatment enhanced the inhibitory potency of the 5-HT1A agonist (+-)-8-hydroxy-2-(di-n propylamino)tetralin HBr (8-OH-DPAT) on DOI-induced HTR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584832 TI - Conditioned withdrawal in environments associated with the presence or absence of morphine. AB - An experiment designed to compare conditioned withdrawal in environments associated with the presence or absence of morphine was conducted in hamsters. For some animals, morphine administration was paired with distinctive environmental cues. For other animals, naloxone-precipitated withdrawal was paired with the distinctive environmental cues. For still other animals, naloxone precipitated withdrawal and the distinctive environmental cues were unpaired. Following 12 days of training, animals were observed for signs of withdrawal (e.g., wet-dog shakes, etc.) in the distinctive environment following vehicle injections. Results indicated that more conditioned withdrawal responses occurred in the environment paired with the absence of morphine (naloxone-precipitated withdrawal) than in the environment paired with morphine administration. PMID- 1584833 TI - Catalepsy induced by striatal acetylcholinesterase inhibition with fasciculin in rats. AB - The acetylcholinesterase inhibitor peptide fasciculin (FAS) was bilaterally injected into the striatum of rats. Twenty-four hours after injection, animals showed a cataleptic syndrome that was potentiated by haloperidol (HAL). The catalepsy was significantly decreased by IP atropine. Biochemically, only an increase of the homovanillic acid in the striatum was found 24 h and 7 days after FAS treatment. Seven days after the intrastriatal FAS injection, there was no HAL potentiation of catalepsy, which was even lower than that of rats treated with IP HAL after intrastriatal injection of saline. Results are interpreted as showing the central role of the cholinergic system in the induction of catalepsy in the rat. PMID- 1584834 TI - Morphine attenuates antipredator ultrasonic vocalizations in mixed-sex rat colonies. AB - Mixed-sex groups of laboratory rats living in a visible burrow system (VBS) emit 18-27 kHz ultrasound and retreat to the burrow when a cat is placed in the open area of the VBS. The total duration of ultrasonic vocalizations was reliably reduced by pretreatment with 5 mg/kg morphine. In a subsequent study using male female colony pairs, presentation of a cat to individual rats in the absence of their colony mate indicated significant gender differences in base frequency, degree of emission, and characteristics of pulses elicited. Specifically, females showed a greater number and duration of vocalizations, of higher frequency (kHz), and with shorter individual pulse durations than males. In the same study, morphine (5 mg/kg) produced a general decrease in the level of ultrasonic emissions in both sexes, reduced the mean base frequency (kHz), and increased the mean duration of individual pulses. These data suggest that endogenous opioid mechanisms may be involved in the mediation of ultrasonic vocalization in response to a predator, and are discussed with reference to known involvement of such systems in defensive responding. PMID- 1584835 TI - Naltrexone-induced aversions: assessment by place conditioning, taste reactivity, and taste avoidance paradigms. AB - The reinforcing/aversive properties of various doses of naltrexone (0.01, 1, and 10 mg/kg) were assessed in three experiments that employed place conditioning, taste reactivity, and taste avoidance paradigms. Naltrexone produced a place aversion and a taste aversion, but did not produce aversive taste reactivity responses, even at the highest dose (10 mg/kg) tested. This suggests that drugs that produce a place aversion do not necessarily produce a conditional dislike for a flavored solution with which they are paired. PMID- 1584836 TI - Chronic hydrochlorothiazide and verapamil effects on motor activity in hypertensive baboons. AB - Spontaneous motor activity was measured in six baboons during chronic oral dosing with a diuretic (hydrochlorothiazide/triamterene), a calcium channel blocker (verapamil), and a combination of the two drugs. Piezoelectric monitors sensitive to movement were attached to leather collars and were worn continuously by the baboons throughout the protocol. Baboons were made hypertensive during a preexperimental period by either 1) chronic administration of deoxycorticosterone acetate (DOCA)-salt or 2) surgical renal artery stenosis. Total inactive periods/day increased over baseline levels during diuretic alone and increased further during diuretic + verapamil combined. The total number of inactive periods/day returned toward baseline levels in the subsequent conditions of verapamil alone and baseline recovery. Activity levels decreased during combination dosing mainly during morning hours (0700-1100 h). Overall changes in activity occurred in the second week of dosing; this time period was found earlier to maximally decrease blood pressure and to impair behavioral performances. PMID- 1584837 TI - Effects of eltoprazine hydrochloride on reactivity to conspecific or novel odors and activity. AB - Treatment with eltoprazine (DU 28853) increased the number of entries by male mice into compartments containing the odors of male and female conspecifics. This effect was most pronounced when odors were provided by previously defeated males. In contrast, the drug had no effect upon responsiveness to the odors of cinnamon and chocolate. The results suggest that eltoprazine may selectively increase reactivity to conspecific odors and that this effect is further enhanced by agonistic experience. Eltoprazine also substantially increased activity levels in all experiments. Since hyperactivity occurred both in the presence and absence of conspecific odors, however, the drug's effects on activity and olfaction seem to be largely independent. The results suggest that the aggression-modulating effects of eltoprazine, as well as other drugs, may be mediated in part by their effects on normal olfactory function. PMID- 1584838 TI - Effects of prepregnancy ethanol on neuromotor development, activity, and learning. AB - This study examines the behavioral consequences of both long-term chronic and acute high-dose administration of ethanol before pregnancy. Female rats were assigned to one of five conditions: a self-administered liquid diet with 35% ethanol-derived calories, a pair-fed liquid diet with 0% ethanol-derived calories, a gavage intubation with 4 g/kg ethanol, a gavage intubation control, or a standard lab chow control. Offspring were weighed at various ages and tested for neuromotor development, activity, and learning a Morris maze water task. Offspring of mothers in the high-dose condition were hyperactive as juveniles but not as adults. Hyperactivity was not seen in the low-dose chronic ethanol condition, contrary to previous reports. Neither ethanol administration paradigm was associated with learning deficits. Prepregnancy stress effects were apparent from both the restricted liquid diet feeding and the gavage treatment on neuromotor development. A possible mechanism for the effects of prepregnancy ethanol treatment is linked to ethanol's potential to alter hormone levels. Since hormones are directly responsible for the maturation of the egg, hormonal imbalances as a result of ethanol exposure may result in developmental deficiencies in the offspring. PMID- 1584840 TI - Antagonism of phencyclidine-induced hyperactivity in mice by elevated brain GABA concentrations. AB - Vigabatrin and (S)-4-allenylGABA (MDL 72483), two anticonvulsant GABA-T inhibitors, partially antagonize phencyclidine (PCP)-induced hyperactivity in mice at doses that do not affect spontaneous motor activity. The PCP antagonism is related to whole-brain GABA concentrations. The results indicate the potential use of GABA-T inhibitors in the therapy of PCP intoxications and perhaps also in the treatment of certain forms of endogenous psychoses. PMID- 1584839 TI - Alarm substance induces convulsions in imipramine-treated rats. AB - Male rats were injected with imipramine (0-30 mg/kg) and subsequently tested in the forced-swim test in either fresh water or water soiled by other rats, which presumably contains an alarm substance. Imipramine did not affect the behavior of rats in fresh water. More than half the animals given the combination of imipramine (30 mg/kg) and stress from alarm substance had clonic convulsions. Adrenalectomy did not affect this relationship. This is the first study demonstrating the potential of an alarm substance for inducing convulsions. PMID- 1584841 TI - Ibotenic acid lesions of medial prefrontal cortex augment swim-stress-induced locomotion. AB - Locomotor activity of rats with sham or ibotenic acid lesions of the medial prefrontal cortex (MPFC) was assessed after animals were exposed to a 15-min swim or control stress. Swim-stress-induced locomotor activity was augmented in the MPFC-lesioned rats. These and other data suggest that lesions of the MPFC are followed by an exaggeration of the normal behavioral response to stress. Dysregulation of dopamine transmission in the basal ganglia may be involved. PMID- 1584842 TI - Effect of stress on oral morphine and fentanyl self-administration in rats. AB - The effect of immobilization stress (15 min/day) or no stress on oral morphine (0.25-0.5 mg/ml) or fentanyl (5-20 micrograms/ml) self-administration was examined in rats. Animals had access to a morphine or fentanyl solution for 4 days, followed by a single-choice day of access to the opioid solution and a separate water bottle. This 5-day cycle was repeated five times for 7 h/day in home cages. Morphine consumption and preference were assessed for an additional 30 days (i.e., six more cycles) in a subgroup of subjects. Plasma corticosterone levels in the stress groups indicated that the stress manipulation was effective. Over the course of the experiment, animals in the stress groups significantly increased their preference for the opioid solutions during choice days compared to nonstress controls. Morphine preference after 55 days was twice as high in the stress group (70% morphine/30% water) in comparison to controls (34% morphine/66% water). These results indicate that stress increases oral opioid self administration in rats. Future directions and the implications of this work are discussed. PMID- 1584843 TI - Supersensitized oral responses to a serotonin agonist in neonatal 6-OHDA-treated rats. AB - Neonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine D1 agonist induction of oral activity. The present study was conducted to determine whether induced oral responses to serotonin (5-HT) agonists would be similarly altered in this rat model. At 3 days after birth, rats received desipramine HCl (20 mg/kg, IP) 1 h before 6-OHDA HBr (100 micrograms in each lateral ventricle) or saline-ascorbic acid (0.1%) vehicle. At approximately 9 mo, rats were challenged with the mixed 5-HT1C and 5 HT2 receptor agonist, m-chlorophenylpiperazine diHCl (m-CPP 2HCl; 0.30-6.0 mg/kg, IP) and were then observed for 1 min every 10 min over a 60-min period. m-CPP induced oral activity in both the vehicle and 6-OHDA groups, with the responses of the 6-OHDA group being much greater. An m-CPP dose of 3.0 mg/kg produced a maximal response of 63.6 +/- 3.2 oral movements in the 6-OHDA group. A bell shaped response curve was obtained, with lower and higher doses of m-CPP producing less of an effect. Attenuation of the m-CPP-induced response by the 5 HT receptor antagonist, mianserin HCl (1.0 mg/kg, IP, 30 min before m-CPP), indicates that the m-CPP effect is receptor mediated. These findings demonstrate that neonatal 6-OHDA treatment produces ontogenic long-lived supersensitization of a 5-HT receptor system in rats. PMID- 1584844 TI - Scopolamine suppresses both locomotion and object contact in a free-exploration situation. AB - It was recently reported by Buhot et al. that presession cholinergic disruption with scopolamine decreases time spent in proximity to novel objects while increasing locomotor behavior. Male Long-Evans rats (Rattus norvegicus, 80 days old) were given low-light access to an arena containing objects but were not forced to remain in the arena. On day 1, each subject was injected with saline (SAL). This session was used for familiarization with the apparatus and procedure. On days 2 and 3, four groups were given saline (SAL) or scopolamine (SCO, 1 mg/kg or 0.25 mg/kg), resulting in SAL-SAL, SAL-SCO, SCO-SAL, and SCO-SCO groups. Videotapes of these sessions were scored according to a standard protocol that allows separate quantification of locomotion, general activity, and object interaction behaviors. Scopolamine suppressed object investigation (both gross contact measures and indices of interaction character) whenever present. In contrast to Buhot et al. (using a forced-exploration situation), in this free exploration context SCO also suppressed locomotor behavior. This study supports the conclusion that anticholinergics impair information gathering instead of affecting memory directly, which calls into question memory-related explanations of cholinergic treatments. PMID- 1584845 TI - Effects of tetrahydroaminoacridine on spatial navigation of nucleus-basalis- and frontal-cortex-lesioned rats. AB - The present study investigates the effects of tetrahydroaminoacridine (THA: 1 and 3 mg/kg) on water maze (WM) spatial learning performance of intact, nucleus basalis- (NB) lesioned, frontal-cortex- (FR) lesioned, or NB + FR-lesioned rats. NB lesions did not impair WM learning and had no effect on the WM performance deficit in FR-lesioned rats. THA at 1 or 3 mg/kg did not improve WM spatial memory of intact, NB-, FR-, or NB + FR-lesioned rats. These results suggest that 1) the cholinergic NB system is not a prerequisite for frontally mediated acquisition of WM performance, 2) THA treatment does not enhance spatial memory, and 3) THA is not effective in alleviating cognitive deficits induced by degeneration of the frontal cortex. PMID- 1584847 TI - Effect of long-term cigarette smoke exposure on locomotor activity and brain monoamine levels in rats. AB - Rats were chronically exposed to cigarette smoke for 20 min twice daily using a smoking machine. On days 1, 4, and 14, locomotor activity and rearing were measured for 15 min in an open-field apparatus. On day 1, exposure to cigarette smoke increased locomotor activity and rearing in the latter half of the observation period. This effect became more pronounced on days 4 and 14. Chronic cigarette smoke exposures for 21 days significantly decreased the norepinephrine levels in the hypothalamus, thalamus, and pons-medulla, but not the levels of dopamine, 5-hydroxytryptamine, or their metabolites. These results suggest that repeated cigarette smoke exposure increasingly stimulates locomotor activity and rearing and affects norepinephrine metabolism, especially in the brainstem. PMID- 1584846 TI - Anxiogenic effects of acute and chronic cocaine administration: neurochemical and behavioral studies. AB - The effects of cocaine on defensive withdrawal behavior in rats and elevated plus maze behavior in mice were investigated. Cocaine (20 mg/kg IP) injected daily for 7 or 14 days induced defensive withdrawal; that is, the latency to emerge from a small chamber in an open field and the mean time in the chamber were both significantly increased. Acute cocaine administration also induced defensive withdrawal, and this effect was prevented by prior treatment with chlordiazepoxide (5 mg/kg IP). Both acute and chronic cocaine treatments significantly increased plasma concentrations of corticosterone and reduced the ratios of 3,4-dihydroxyphenylacetic acid to dopamine and 5-hydroxyindoleacetic acid to serotonin in several brain regions. Further evidence for an acute anxiogenic effect of cocaine was obtained from mice studied in the elevated plus maze. Acute cocaine administration decreased both the number of entries into and the time spent in the open arms of the maze. These results taken together strongly support an anxiogenic action of acute and chronic cocaine administration. PMID- 1584848 TI - Effects of 5-HT3 antagonists on fixed-interval behavior in rats. AB - The effects of 5-hydroxytryptamine3 (5-HT3) antagonists were studied in rats responding under a fixed-interval (FI) schedule of food presentation. BRL 43694, GR 38032F, ICS-205,930 and zacopride had no effect on FI responding up to 10.0 mg/kg IP. Response rate decreases were observed only at high doses (30.0 or 56.0 mg/kg); rate increases were not observed. In comparison, caffeine (1.0-10.0 mg/kg) and cocaine (3.0-18.0 mg/kg) increased and lorazepam (0.3 mg/kg) decreased FI responding. The effects of caffeine, cocaine, and lorazepam were unchanged when coadministered with the 5-HT3 antagonists. The results show that 5-HT3 antagonists, when given alone or with other CNS-active drugs, have little effect on FI responding of rats. PMID- 1584849 TI - Ethanol's antiseizure efficacy is reduced by stress. AB - The ability of ethanol to antagonize the electrical precipitation of seizures in an incremental electroconvulsive shock paradigm was examined in groups of stressed and control mice. In stressed mice, the dose-response curve for ethanol's antiseizure efficacy was down-shifted and right-shifted relative to controls. These data may have clinical implications with respect to the interaction between stress, ethanol, and proneness to seizures. PMID- 1584850 TI - The aged and the aging of physical therapy. PMID- 1584851 TI - The impact of physical therapy on nursing home patient outcomes. AB - The objective of this retrospective study was to assess the intensity and outcome of individual components of interdisciplinary care, including physical therapy, in a teaching nursing home. Two independent reviewers abstracted records from 90 consecutive patients admitted to the nursing home. They rated intensity and outcome of each program component using a structured, standardized data abstraction form. Program components were physical therapy, speech therapy, psychosocial therapy, medication adjustment, and other medical and nursing care. Physical therapy and medication adjustment were the most frequently received therapies. Eighty-eight percent of the patients receiving high-intensity physical therapy and 33% of the patients receiving moderate-intensity physical therapy improved. For medication adjustment, 93% and 72% of the high- and moderate intensity groups, respectively, improved. In univariate analyses, physical therapy intensity and age were associated with improvement. Baseline function in activities of daily living and cognitive function were not associated with physical therapy outcome. A stepwise multiple logistic regression analysis revealed that only therapy intensity was associated with improved outcome. We conclude that physical therapy was efficacious for patients receiving high intensity treatment. Advanced age, activities-of-daily-living status, and cognitive impairment were not associated with poor physical therapy outcome. PMID- 1584852 TI - Effect of air-splint application on soleus muscle motoneuron reflex excitability in nondisabled subjects and subjects with cerebrovascular accidents. AB - We investigated the effect of air-splint pressure on soleus muscle motoneuron reflex excitability in 18 nondisabled subjects with no history of neurological disease and 8 subjects with cerebrovascular accidents (CVAs). Motoneuron reflex excitability was assessed by measuring the percentage of amplitude (peak-to-peak measurement) change in the Hoffman reflex (H-reflex). Pressure was applied for 5 minutes, after which the air-splint was deflated. Ten H-reflexes were recorded and averaged for each subject before pressure application to obtain a baseline value. H-reflexes were also recorded at set intervals during and after pressure application. Two-way analyses of variance for repeated measures were used to compare each group's pressure and postpressure measurements with the baseline value. Significant F tests were followed by post hoc t tests. Analyses of variance were used to compare the nondisabled subjects' H-reflex recordings with those obtained for the subjects with CVAs. The nondisabled subjects demonstrated reductions of 55% at 1 minute, 52% at 3 minutes, and 40% at the fifth minute of pressure application. The postpressure measurements showed increases in the reflex amplitude at 1 and 3 minutes postpressure; however, by the fifth minute, the amplitude was not different from the baseline value. The subjects with CVAs demonstrated reductions of 41% at 1 minute, 48% at 3 minutes, and 52% at 5 minutes of pressure application. None of the postpressure measurements, however, were statistically different from the baseline value. A statistically significant difference was demonstrated between the nondisabled subjects and the subjects with CVAs at the first minute of pressure release.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584853 TI - Applicability of the hierarchical scales of the Tufts Assessment of Motor Performance for school-aged children and adults with disabilities. AB - The relative difficulty of motor performance tasks for school-aged children and adults with physical disabilities within a standardized motor performance test was examined. The Tufts Assessment of Motor Performance (TAMP) was administered to 69 children (ages 6-18 years, X = 12.1, SD = 3.9) and 137 adults (ages 19-83 years, X = 46.7, SD = 20.0) with neurological and musculoskeletal impairments. The purpose of the study was to determine whether the hierarchical scales of the motor performance tasks between the pediatric and adult disability samples were congruent. Correlations of task difficulty calibrations (r = .76; P less than .01) and task rank ordering (rho = .76; P less than .01) were moderately high and positive between pediatric and adult subjects. Significant age-group differences emerged in relation to a number of individual motor performance tasks. In general, mobility and ambulation tasks were relatively easier for children, whereas manipulation tasks were relatively easier for adults. The data suggest a strong similarity in the overall pattern of motor performance task difficulty for children and adults. The results support the use by physical therapists of two parallel versions of the TAMP to describe the motor performance of adults and school-aged children with physical disabilities. PMID- 1584854 TI - An electromyographic analysis of hip abductor muscle activity when subjects are carrying loads in one or both hands. AB - Forces produced at the hip joint as a result of hip abductor muscle contractions while carrying loads reach several times body weight (BW). Physical therapists often advise patients with hip osteoarthritis in ways to minimize these forces as a means of reducing the pain associated with carrying loads. The purpose of this study was to use surface electromyography (EMG) to quantify the relative demands placed on the hip abductors while carrying loads in one hand or in both hands. Thirty asymptomatic college-aged subjects walked while carrying loads of 10% and 20% of BW unilaterally and loads of 10%, 20%, and 40% of BW bilaterally. Signals from foot switches allowed a computer to average the EMG data over the phase of gait when the foot was in complete contact with the ground. All EMG data were normalized to a percentage of the EMG voltage produced during no-load walking (%EMG). Our prime dependent variable was the %EMG averaged over both hip sides of all subjects' multiple walking trials. Our major analysis involved a multifactorial analysis of variance for repeated measures with method of carry (unilateral or bilateral) and load as the two main independent variables. Results demonstrated that both the amount of the load and the method of load carry made a significant difference in regard to the amount of hip abductor EMG produced. Of particular note was the fact that the bilateral 20% of BW condition produced statistically less %EMG (when averaged over both sides) than did the unilateral 20% of BW condition. Persons with hip disease should be aware that hip joint forces may be reduced by the bilateral method of carrying loads. PMID- 1584855 TI - Lumbar support thickness: effect on seated buttock pressure in individuals with and without spinal cord injury. AB - We compared the effects of different lumbar support thicknesses on seated buttock pressure in individuals with and without spinal cord injury (SCI). Eighteen subjects with SCI (SCI group) and 18 subjects without SCI (control group) were seated on a pressure-sensing transducer incorporated into an adjustable chair. The output was calibrated so that eight pressure intervals (colors) were displayed. The lumbar support thickness was adjusted to 0, 2.5, 5, and 7.5 cm, and the highest and lowest seated buttock pressures were analyzed. External measurements of the hip angle were taken for each lumbar support condition. High reliability of repeated seated test positions was found (intraclass correlation coefficient = .93). The 5- and 7.5-cm-thick lumbar supports caused a decrease in the highest pressure areas in the control group, but no change in the SCI group. The hip angle was increased with each increment in lumbar support thickness in both groups, but the SCI group's hip angle was consistently less than that of the control group for each lumbar support condition. The results of this study suggest that in individuals with chronic paralysis (greater than or equal to 3 years), the use of a wheelchair lumbar support has a negligible effect on seated buttock pressure. PMID- 1584856 TI - The electrical effect of two commonly used clinical stimulators on traumatic edema in rats. AB - The purposes of this study were to determine the effect of electrical stimulation on traumatic rat hind-paw edema and to establish whether there would be a difference in edema reduction when two types of stimulators were used. The animals were divided into a control group (n = 15) and two experimental groups, one group receiving monophasic pulsed current (MPC group, n = 15) and the other group receiving symmetrical biphasic pulsed current (SBPC group, n = 14). The right hind-paw volume of all groups was measured prior to traumatization and at 24, 48, 72, and 96 hours posttrauma. Following the 24-, 48-, and 72-hour measurements, 1 hour of electrical stimulation was administered to the experimental groups. The control group received sham treatment. Results revealed significant edema reduction in all groups over the 96-hour period, with each group's greatest change in paw volume occurring 48 hours posttrauma. At the final paw volume measurement, there was no significant difference between the MPC and control groups or between the MPC and SBPC groups. The SBPC group, however, showed less reduction in edema than did the control group. One hour of electrical stimulation per day over 3 consecutive days failed to demonstrate significant edema reduction in either the MPC group or the SBPC group as compared with the control group. The results of this study demonstrated that the electrical stimulation characteristics and procedures currently used in the clinic do not significantly reduce extant edema caused by trauma in rat hind limbs. PMID- 1584857 TI - Our identity and the power of touch. PMID- 1584858 TI - Improvement in attitudes toward the elderly following traditional and geriatric mock clinics for physical therapy students. AB - The purpose of this study was to determine whether the attitudes of students in a physical therapy education program toward the elderly could be influenced positively by (1) having classroom discussion led by an individual with expertise in geriatrics and (2) having only individuals aged 65 years or older participate in a specially designed geriatric mock clinic (GMC). Subjects were 47 first-year students divided into a control group (n = 24) and an experimental group (n = 23). Students in the control group participated in two 4-week clinical rotations. Students in the experimental group participated in one 5-week clinical rotation and in one 3-week GMC. Students in both groups were given a pretest and a posttest administration of the Kogan Old People Scale to assess their attitudes toward the elderly. No significant difference was found between the two groups' overall attitude scores on the pretest or the posttest results. Overall, positive attitude scores increased significantly for both groups, although the increase was greater for the experimental group than for the control group. Negative attitude scores decreased significantly for the experimental group, but did not change for the control group. We concluded that both traditional clinical rotations and a specially designed GMC influenced the students positively. Suggestions have been made for the Clinical Instructor who wishes to influence physical therapy students' attitudes to meet the increasing needs of the elderly patient population. PMID- 1584859 TI - Effects of low voltage pulsed current on edema formation in frog hind limbs following impact injury. AB - The purpose of this study was to test the effect of low voltage pulsed current (LVPC) on posttraumatic edema formation in frog hind limbs. Feet of 26 anesthetized bullfrogs were systematically injured by weight drop. One hind limb of each animal was randomly selected to receive continuous 100-pps LVPC at 90% of motor threshold; the opposite hind limb served as a control. A series of four 30 minute treatments (interrupted by 30-minute rests) was begun minutes after injury. Changes from pretrauma limb volumes were determined before and after each treatment and at 8, 17, 20, and 24 hours posttrauma. Analysis of variance revealed no significant treatment effect. Similar studies utilizing high voltage pulsed current (HVPC) at 90% of motor threshold revealed significant curbing of edema formation in frogs. Waveform (LVPC versus HVPC) seems to influence the efficacy of electrotherapy for edema control. PMID- 1584860 TI - Measurement of reactive vasodilation during cold gel pack application to nontraumatized ankles. AB - Conflicting results regarding local vascular response during cryotherapy have been reported in the literature. The purpose of this study was to determine whether application of a cold pack reduced blood volume in a nontraumatized ankle. Thirteen subjects ranging in age from 18 to 30 years (X = 22; SD = 3.9) participated in the study. An impedance plethysmograph, in combination with venous occlusion, was used to measure the changes in local blood volume at the ankle over a 20-minute period for the following three conditions: rest, room temperature gel pack application, and cold gel pack application. A significant reduction in local blood volume was found for the cold gel pack condition in comparison with the resting condition. This reduction was attributed to a combination of pressure from the weight of the cold gel pack and the pack's temperature. Maximum decrease in blood volume occurred at 13.5 minutes after cold gel pack application. Reactive vasodilation was not observed. The results lend support to the clinical use of a cold gel pack when a reduction in local circulation is desired, such as in the management of acute-phase soft tissue trauma. PMID- 1584861 TI - Reproducibility and accuracy of angle measurements obtained under static conditions with the Motion Analysis video system. AB - The development of computerized and semi-automated motion analysis systems has made the study of human motion more widely available in research and clinical settings. Although many of these systems are currently used by physical therapists, the accuracy and reproducibility of some of these systems in estimating joint angles have not been reported. In this study, the accuracy and reproducibility of angle measurements obtained by use of the Motion Analysis video system were evaluated under static conditions using a standard goniometer. Reflective markers placed on a goniometer were recorded by two video cameras at 17 angles, from 20 to 180 degrees, in 10-degree increments. Recordings of the goniometer were made at three locations within the field of view of the cameras. The intraclass correlation coefficient for each location tested was .99. Average within-trial variability was less than 0.4 degree at all locations. A linear regression of the system-calculated angles and reference angles for all locations had slopes near unity (ie, 1) and intercepts that were not statistically different from zero. A preliminary evaluation of the system under dynamic conditions revealed that distances were slightly underestimated, regardless of where the movement occurred within the calibration cube. PMID- 1584862 TI - The dual-task methodology and assessing the attentional demands of ambulation with walking devices. AB - The purposes of this article are (1) to provide a preliminary examination of the attentional demands of ambulating with two commonly prescribed walking aids (a standard walker and a rolling walker) and (2) to introduce the dual-task methodology to the physical therapy community. Five subjects familiar with the appropriate use of the walkers and five subjects uninformed as to the correct use of the walkers participated in the study. Each subject completed the three phases of the experiment: (1) performing the reaction time (RT) task only; (2) performing each of the walking tasks only; and (3) performing each of the walking tasks in conjunction with the RT task, which constituted the dual-task conditions. The findings indicated that walking aided by either the rolling walker or the standard walker was highly attention demanding. More importantly, it appears that greater attentional demand was required when ambulating with the standard walker. These results are discussed with respect to the gait modifications and accuracy demands required when using these walkers. The usefulness of the dual-task methodology as a research tool for addressing clinically oriented questions is emphasized, and some potential applications of this methodology for the therapist within the clinic are discussed. PMID- 1584863 TI - Early free-flap coverage of electrical and thermal burns. AB - Because of the clinical concept of progressive tissue necrosis, the concept of immediate excision and coverage of high-tension electrical burns and deep thermal burns has been a controversial subject. Recent clinical and laboratory research has cast doubt on this concept. We present a series of five patients who suffered severe extremity electrical and thermal injuries in whom early excisions were performed with immediate free-flap reconstruction. Special importance is given to radical debridement of all questionably nonviable tissues, excepting intact tendons, nerves, and bone. In these tissues, anatomic continuity is more important than apparent viability. No infections or wound-healing complications were seen as a result of this protocol. Of eight digital nerves that did not function at the initial examination, five subsequently recovered two-point discrimination of less than 10 mm. PMID- 1584864 TI - Eighty-four consecutive breast reconstructions using a textured silicone tissue expander. AB - Breast reconstruction utilizing smooth-surface silicone tissue expanders is associated with certain problems. Significant capsular contracture may develop around the expander with subsequent expander displacement necessitating repositioning or capsulectomy at the time of expander removal. Infection, pain on expansion, chest-wall compression, and complications related to the remote fill valve also have been reported. A textured-surface silicone expander with an integrated fill valve was developed to address these issues. Eighty-four consecutive breast reconstructions were performed by a single surgeon using textured expanders in 55 patients. Intraexpander pressures were measured during expansion for a group of these patients, and both initial and postinflation pressure readings were quite low (average initial pressure 2.88 mmHg; average postinflation pressure 12.87 mmHg). Eighty-one of the reconstructions have been completed without any expander losses and with minimal complications. Tissue expander volume averaged 580 cc, and the expansion duration averaged 5.6 months. Various types and configurations of permanent implants were used to complete the reconstructions. Eighty-four percent of our patients' completed reconstructions (including nippleareola reconstruction and opposite breast alteration, when necessary) were accomplished with just two procedures. Seventeen long-term adjustable textured-surface expander/implants with anatomic breast shape are still in place, all after only one operation. The inframmary fold has generally been established passively by the expansion process alone. Textured-surface silicone expanders have stayed where positioned, have expanded easily with minimal patient pain, and have created a noncontractile soft-tissue cover for the final implant. The textured expander with an integrated fill valve has simplified breast reconstruction by helping to limit the problems encountered with smooth silicone expanders. The resulting reconstructions have remained soft with a very acceptable aesthetic appearance. The patient office and hospital charts and photographs of this consecutive series were notarized and submitted to the Editor of this Journal, whose biostatistician randomly selected the cases illustrated. PMID- 1584865 TI - The biophysical and histologic properties of capsules formed by smooth and textured silicone implants in the rabbit. AB - Capsular contracture remains the major complication of reconstructive and aesthetic breast surgery. The purpose of this investigation was to determine if a silicone implant with a textured surface will form a capsule of significantly different biophysical and histologic properties than conventional smooth silicone. Thirty smooth and 30 textured silicone tissue expanders were implanted under the panniculus carnosus of rabbits. After 3 months, measurements related to contracture were performed on anesthetized animals in an investigator-blinded, controlled manner. Intraexpander pressures were measured as saline was injected over time. We found a significant correlation between intraexpander pressures, applanation tonometry, and Baker class. Histology revealed a thicker, more adherent, and inflammatory capsule around the textured silicone implants as compared with the smooth silicone implants. Dynamic pressures were plotted against volume of saline within the two types of implants. Statistical analysis revealed that the textured implants form a tighter and thicker capsule than the smooth implants after 3 months of observation (p less than 0.005). PMID- 1584866 TI - The SMAS and the nasolabial fold. AB - In a series of histologic sections and clinical and cadaver dissections, the superficial musculoaponeurotic system (SMAS) is seen to become the investing fascia of the zygomaticus major and minor muscles in the medial cheek. The pull on the cheek flap during rhytidectomy is diffused by the attachment of the SMAS to these muscles. I believe that this attachment accounts for the minimal change in the nasolabial crease after a Skoog-type sub-SMAS face lift. PMID- 1584867 TI - Columellar elongation in bilateral cleft lip repair: early results. AB - Flattening of the nasal tip and shortness of the columella are two of the deformities that remain following successful repair of a bilateral cleft of the lip. Until now, correction has not been possible without producing undesirable scars on the surface of the nose or lip. A three-dimensional Z-plasty on the alar rim achieves columellar lengthening and forward projection of the tip, but it does not have these disadvantages. PMID- 1584868 TI - Myocutaneous flap ischemia: flow dynamics following venous and arterial obstruction. AB - To further clarify the pathogenesis of the poorer prognosis in skin flaps exposed to venous stasis compared with arterial insufficiency, a microsphere study was conducted in bilateral rectus abdominis island flaps in seven pigs. The relationship between capillary blood flow and arteriovenous (A-V) shunting was studied during progressive 1-hour intervals of arterial insufficiency and venous stasis and during 3 hours of reperfusion. Under controlled conditions, total blood flow was reduced from 100 percent to both 50 and 25 percent by application of an adjustable clamp on the artery supplying one flap and on the vein draining the contralateral flap. The relative distribution between A-V shunt flow and capillary blood flow was different in arterial insufficiency when compared with venous stasis at both the 50 percent and the 25 percent blood flow levels. In the arterial insufficiency flaps, the A-V shunt flow and capillary blood flow shared the total blood flow in the following percentages: 64/36 (at 100 percent total blood flow), 44/56 (at 50 percent total blood flow level), and 22/78 (at 25 percent total blood flow level). In the venous stasis flaps, the A-V shunt flow and the capillary blood flow shared the total blood flow in percentages of 70/30, 66/34, and 55/45, respectively. Hence, in arterial insufficiency flaps, capillary blood flow was spared by a relatively greater decline in A-V shunting compared with venous stasis flaps. Redistribution of capillary blood flow from subcutaneous tissue to muscle was observed, whereas blood flow was equally distributed throughout the length of the flaps at all flow levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584869 TI - Cyclophosphamide-induced neutropenia: effect on postischemic skin-flap survival. AB - In a blinded study, 24 pigs were randomized to a 5-day preoperative treatment regimen of cyclophosphamide (n = 12) or placebo (n = 12). At operation, buttock cutaneous and latissimus dorsi myocutaneous flaps were created and then subjected to 6 hours of global ischemia. After 24 hours of reperfusion, flap skin and muscle survivals were determined. All cyclophosphamide-treated animals were rendered neutropenic (less than 500 neutrophils/mm3 of peripheral blood). The results show that neutropenia had no effect on postischemic buttock cutaneous flap survival. In contrast, cyclophosphamide-induced neutropenia demonstrated a significant protective effect on postischemic latissimus dorsi myocutaneous flap survival. This study further implicates the neutrophil as a significant factor in the mediation of ischemia/reperfusion injury of myocutaneous flaps. PMID- 1584870 TI - Effect of allopurinol on the survival of experimental pig flaps. AB - Allopurinol has been reported to improve cell survival in a variety of conditions, including the ischemia-reperfusion injury occurring in skin flaps. It has been suggested that the beneficial effect of allopurinol on rat skin flaps is through blockage of xanthine oxidase-generated oxygen-derived free radicals. We have previously reported on the lack of xanthine oxidase activity in the skin of humans and pigs as compared with that of rats. This current study attempts to improve skin and myocutaneous flap survival in pigs in two separate experiments using allopurinol. In the first experiment, a suspension of 50 mg/kg (N = 12) allopurinol resulted in no significant difference in the survival of control and treated flaps. Because of the negative results in the first experiment, a second experiment was designed making several changes. The length of the global ischemic insult was reduced from 8 to 6 hours, and allopurinol was administered as a solution of 300 mg/kg (N = 14). This higher dose is expected to produce complete inhibition of xanthine oxidase in this animal model. These changes resulted in three operative deaths, no improvement in skin-flap survival, and a decrease in myocutaneous flap survival. Allopurinol's therapeutic effectiveness and its mechanism of action in an ischemia-reperfusion injury model lacking xanthine oxidase activity are discussed. PMID- 1584871 TI - Capillary blood perfusion during postischemic reperfusion in striated muscle. AB - Monitoring of nutritive blood flow in muscle is of particular importance to reconstructive surgeons, since ischemia/reperfusion in striated muscle is known to result in postischemic microvascular perfusion failure. Laser Doppler flowmetry has recently been introduced as an easy-to-use, noninvasive technique for continuous monitoring of microvascular tissue perfusion. Despite its popularity, there exists a great deal of controversy as to what actually generates the laser Doppler signal recorded from a given tissue. Intravital microscopy is a technique for direct visualization of the nutritional circulation in tissue. By using intravital microscopy, direct measurements of blood perfusion in individual segments of the nutritional microcirculation can be made. In 22 Syrian golden hamsters we performed laser Doppler flowmetry and intravital microscopy measurements in muscle tissue prior to and during reperfusion after 4 hours of tourniquet ischemia using the dorsal skinfold chamber model. Intravital microscopy (n = 10) revealed a heterogeneous capillary perfusion during the early reperfusion phase with a decrease (p less than 0.01) in functional capillary density to 49.4 +/- 17.0 percent of control. No recovery was observed after 24 hours of reperfusion. Laser Doppler flowmetry (n = 12) showed a parallel reduction of capillary red blood cell flux during the early perfusion phase to 43.9 +/- 22.6 percent of control values (p less than 0.01), and no recovery was observed after 24 hours of reperfusion. However, the laser Doppler flowmetry technique was not able to detect the capillary perfusion inhomogeneities shown by intravital microscopy. Postischemic reperfusion in striated muscle is characterized by a decrease in functional capillary density and a heterogeneous capillary perfusion. Laser Doppler flowmetry is a useful tool for monitoring microvascular tissue perfusion, although in striated muscle of the hamster it must be considered that accurate nutritional "capillary" flow readings can be grossly overestimated if larger vessels, such as arterioles and collecting venules, are contained in the measuring field of the laser Doppler probe. PMID- 1584872 TI - Skin island flaps supplied by the vascular axis of the sensitive superficial nerves: anatomic study and clinical experience in the leg. AB - An anatomic study performed on 64 fresh injected legs has shown the role of the vascular axis that follows the superficial sensitive nerves in supplying the skin. Three nerves were studied: the saphenous nerve, the superficial peroneal nerve, and the sural nerve. Conclusions are the same for the three nerves: The vascular axis, which can be either a true artery or an interlacing network, ensures the vascularization of the nerves, gives off several cutaneous branches in the suprafascial course of the nerve, and anastomoses with the septocutaneous arteries issuing from a deep main vessel. The superficial nerves that course the leg can therefore be considered as vascular relays owing to their neurocutaneous arteries. The concept of a neuroskin island flap has been developed and applied to six clinical cases for coverage of some specific areas of the knee and of the lower part of the limb. PMID- 1584873 TI - The metabolism of skin grafts stored with excess carbon dioxide. AB - In Japan, the long-term storage of cereals and foods in the presence of excess carbon dioxide is already a practical reality. The present study was conducted to assess the metabolic changes in skin grafts during storage in the presence and absence of excess carbon dioxide, with the aim of seeking a simple and effective method to prolong skin-graft viability during storage. In experiment 1, 120 male Wistar rats weighing 250 to 300 gm were used. A split-thickness skin graft 450 microns in thickness was harvested from the back of each rat with a dermatome and was divided into two pieces for separate storage. One piece was stored in normal air at 4 degrees C (control grafts), and the other was stored in a gas mixture composed of 20% O2, 20% CO2, and 60% N2 at 4 degrees C (CO2 grafts). Metabolic changes in the skin grafts during storage were investigated by ATP and glucose assays. In experiment 2, 60 male Wistar rats were used. Collection and storage of the split-thickness skin grafts were performed as in experiment 1. In both groups, skin grafts were stored for 1, 2, or 3 weeks, and the oxygen consumption rate of each graft was determined. Experiment 3 used 80 male Wistar rats and the same procedure as in experiment 1; split-thickness skin grafts were harvested, divided into two pieces, and stored for 1, 2, or 3 weeks. In both groups, the stored skin grafts were regrafted onto the backs of the same donor rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584874 TI - Russia: change and opportunity. PMID- 1584875 TI - From Russia with love. PMID- 1584876 TI - The value of basic education in plastic surgery: a lesson learned from abroad. PMID- 1584877 TI - Human allotransplant of a digital flexion system vascularized on the ulnar pedicle: a preliminary report and 1-year follow-up of two cases. AB - Two cases of a human vascularized allotransplant of a complete digital flexion system are reported with detailed descriptions of the dissection technique and postoperative treatment. Satisfactory functional results open new prospects for this type of transplantation surgery. PMID- 1584878 TI - Commissure stabilization appliance in facial reanimation surgery. AB - A modified maxillary appliance is described that provides an inexpensive intraoral method of commissure stabilization which effectively prevents transmission of stretching forces onto the delicate anastomoses and muscle insertion at the commissure and upper lip in the immediate and early postoperative period. It is well tolerated by the patient, does not interfere with eating, and may be carefully removed for periodic cleaning. It is a simple technique that adds an increased measure of flap security without any risk of morbidity. PMID- 1584879 TI - Aesthetic surgery on psychologically disturbed patients. PMID- 1584880 TI - Surgical management of divided nevus of the eyelid. PMID- 1584881 TI - Transconjunctival lower eyelid blepharoplasty. PMID- 1584882 TI - Plastic surgeon as an ostrich in the surgical treatment of cleft palate. PMID- 1584883 TI - Free tongue graft for correcting cleft lip deformities. PMID- 1584884 TI - An unassisted inferior pedicle reduction mammaplasty: a simplified technique for reduction in time and blood loss. PMID- 1584885 TI - Correcting the inverted nipple. PMID- 1584886 TI - Definite diagnosis of breast implant rupture by ultrasonography: instrumentation and user requirements. PMID- 1584887 TI - Personal experiences with Toradol. PMID- 1584888 TI - Priority of phalloplasty by forearm flap. PMID- 1584889 TI - The Sormann-Lim tendon approximator. PMID- 1584891 TI - Injection of commercially accessible silicone in body sculpturing. PMID- 1584892 TI - Correction of inverted nipple with periductal fibrous flaps. PMID- 1584893 TI - Nonsurgical repair of perinasal skin defects. PMID- 1584894 TI - Coping and adaptation in pancreatectomized patients: a somatopsychic perspective. AB - The present study describes various strategies of coping with illness as observed in pancreatectomy patients, a group of patients which has not been investigated before in this field of research. Questionnaire data obtained from a sample of n = 134 were analyzed with regard to sociodemographic (age, sex) and medical characteristics (indication for surgery: chronic pancreatitis vs. pancreatic carcinoma; outcome after surgery: diabetes, hypoglycemia, pain). The relationships between ways of coping and several adaptation criteria were investigated. The question is put up to discussion, if it is possible to clearly separate emotion as a way of coping and emotion as an outcome of coping. PMID- 1584895 TI - Sexuality and menopause. AB - Postmenopausal sexuoerotic health is multivariately determined by both intrinsic and extrinsic variables, some of which may predate the menopause. In a pilot study of 20 postmenopausal women, even when deterioration in sexual well-being was anticipated beforehand, it did not inevitably materialize, but if it did so, it was not inevitably correlated with diminished partner availability. Postmenopausal ratings of erotosexual ideation, imagery, and practices indicated nondeterioration markedly more often than they did deterioration. There is increasing professional agreement that androgen maintains erotosexual functioning in women as well as men; and that, in minimal nonmasculinizing dosage, it can be included with good therapeutic effect in postmenopausal steroid replacement therapy. PMID- 1584896 TI - How much longer must medicine's science be bound by a seventeenth century world view? AB - The exclusion of nonmaterial human phenomena mandated by medical science's continuing allegiance to a 17th century scientific world view has constituted a major obstacle to medicine's scientific maturation as a human discipline. But 20th century conceptual changes even in physics (not to mention the influence of the theory of evolution) now renders that exclusion untenable and in effect legitimizes efforts to devise scientific means appropriate for the human domain. Practical as well as theoretical issues involved in such an undertaking are discussed within the framework of a 20th century scientific world view as represented by the biopsychosocial model, a counterpart to the traditional biomedical model. PMID- 1584897 TI - The Revised Toronto Alexithymia Scale: some reliability, validity, and normative data. AB - Addressing certain problems with the compositional structure of the self-report Toronto Alexithymia Scale, this paper reports the development of a revised version of the scale as well as results from a preliminary series of studies evaluating its reliability and validity. The Revised Toronto Alexithymia Scale (TAS-R) demonstrated good internal consistency and a stable and replicable two factor structure that is congruent with the two major dimensions of the alexithymia construct. Evidence of convergent and discriminant validity for the TAS-R was provided by correlations with measures of other constructs. Criterion validity was demonstrated by the ability of TAS-R scores to discriminate between behavioral medicine outpatients designated alexithymic and those designated non alexithymic on the basis of clinical interview ratings. Normative data are provided for university student, normal adult, and psychiatric outpatient populations. PMID- 1584898 TI - Psychosomatic problems surrounding kidney transplantation. Incidence of alexithymia and psychiatric disturbances. AB - Psychosomatic problems surrounding kidney transplantation were examined in 16 recipients. Either alexithymia or psychiatric disturbances were observed in 93.8% (15 cases) recipients. The incidence of psychiatric disturbances during pre- and posttransplant periods was 43.8% (7 cases) and 18.8% (3 cases), respectively; that of alexithymia was 31.3 and 6.3%. None of the 7 cases with psychiatric disturbances before transplant manifested any disturbances after transplant, whereas 3 of the 9 cases without psychiatric disturbances showed psychiatric disturbances after transplant. Most psychiatric disturbances after transplant were related to a depressive state. These results indicate that psychiatric symptoms before transplant are not associated with induction of posttransplant psychosis, suggesting that coping with depression due to postoperative rejection may be more important in the future. PMID- 1584899 TI - The influence of defense mechanisms on secondary alexithymia in hemodialysis patients. AB - The influence of psychodynamic aspects such as the defense mechanisms for conflict on secondary alexithymia in hemodialysis (HD) patients was examined among 35 HD patients and their family members. Although HD patients had quite strong conflicts due to HD therapy, the manifestation of conflict and expressiveness toward the family were significantly lower in HD patients with alexithymia than in those without alexithymia. Significantly positive and negative correlations were observed between conflict and expressiveness, and between expressiveness and degree of alexithymia, respectively. These results suggest that this defense mechanism strongly suppresses the manifestation of conflict, and that secondary alexithymia in HD patients may be derived from defense mechanisms such as denial. PMID- 1584900 TI - Increase of medical hospital length of stay by depression in stroke and amputation patients: a pilot study. AB - Past studies have found that medical patients with the diagnosis of depression (comorbidity) have longer hospital lengths of stay (LOS) than those without the diagnosis of depression. This suggested that scores on a depression scale would be positively correlated with LOS. On a rehabilitation ward, 14 stroke and 17 amputee patients were given the Geriatric Depression Scale (GDS) and lengths of stay were recorded. Correlations between GDS scores and LOS were +0.575 for stroke and +0.266 for amputee patients, both in the hypothesized direction. Explanations considered included: (1) depression and medical illness each produce morbidity which summate to require increased LOS; (2) depression delays medical recovery as well as the appearance of medical recovery, and (3) discharge planning is complicated by depression. When depression is associated with inpatient medical illness, DRGs may need to be reevaluated. PMID- 1584901 TI - Selection criteria for brief dynamic psychotherapy: reliability, factor structure and long-term predictive validity. AB - Forty outpatients were evaluated for psychotherapy with a modified version of Sifneos' selection criteria for brief dynamic psychotherapy. Reliabilities were acceptable for most items when the ratings of 4 clinical judges were averaged. A factor analysis of the reliable items produced four of the five dimensions of suitability proposed by Sifneos and others: circumscribed focus, motivation, flexible interaction, quality of interpersonal relations. A combination of these dimensions were more significant predictors of long-term dynamic change than background and DSM-III axis I-V variables. Problem solving capacity (use of self understanding) before treatment could not be reliably rated and was accordingly not tested as a possible fifth dimension of suitability. PMID- 1584902 TI - A comparison of alexithymia in American and Japanese dialysis patients. AB - A comparison of alexithymia in American and Japanese dialysis patients was performed using the Beth Israel Hospital Questionnaire (BIQ) and the MMPI Alexithymia Scale (MMPI-AS) including structured interviews. No significant differences between the USA and Japan were observed in all dialysis patients with both BIQ and MMPI-AS. However, the alexithymia score in US hemodialysis (HD) patients was significantly lower than that in Japanese HD patients, whereas the alexithymia score in American continuous ambulatory peritoneal dialysis (CAPD) patients was significantly higher than that in Japanese CAPD patients. These results may suggest the possibility that the differences in dialysis policy between USA and Japan have secondary effects on alexithymia, which is one of the psychosomatic factors reflecting self-control ability in dialysis patients. PMID- 1584903 TI - Conventional chest radiographs: anatomic understanding of newer observations. AB - Despite the advances in medical imaging modalities over the past several years, conventional chest radiography still remains the most commonly performed imaging examination. In this report, the author discusses four radiographic observations, all visible on the conventional chest radiograph, and the anatomic basis for each: (a) the normal apical opacity, produced by the subclavian artery and easily confused with parenchymal abnormality; (b) vascular reorientation with upper lobe volume loss, a characteristic divergent or parallel pattern helpful in recognizing upper lobe volume loss; (c) extrapleural fat, which simulates pleural plaques along the lateral chest walls and pleural thickening at the chest apices; and (d) mobility of the mediastinum, which contributes to incorrect mediastinal mass localization and creates soft-tissue bands in the retrosternal area. PMID- 1584904 TI - Selected topics in chest trauma. PMID- 1584905 TI - Answering unanswered questions: proposal for a shared resource in clinical diagnostic radiology research. PMID- 1584906 TI - Pneumatic versus hydrostatic reduction of intussusception. PMID- 1584907 TI - Determination of prostate volume with transrectal US for cancer screening. PMID- 1584908 TI - Digital mammography and related technologies: a perspective from the National Cancer Institute. AB - The National Cancer Institute held a workshop entitled "Breast Imaging: State-of the-Art and Technologies of the Future" in September 1991. This article describes some of the presentations given at the workshop as well as relevant data in the literature and discusses their implications. The workshop faculty identified digital mammography as the evolving technology with the greatest potential impact on management of breast cancer. On the basis of the workshop findings and literature review, the author proposed to form the National Digital Mammography Development Group, which will stimulate research in digital mammography and its integration with related technologies: image processing for improved lesion contrast, automated computer-aided diagnosis for enhanced breast cancer detection and characterization, and teleradiology for facilitated radiologic consultation with recognized experts in the field. It is expected that the National Digital Mammography Development Group will facilitate transfer of advanced digital imaging technology to breast cancer clinics. PMID- 1584909 TI - Stereotaxic core biopsy of breast lesions. AB - In 70 selected patients with suspect breast lesions at mammography, accurate, high-speed stereotaxic core-cut biopsy (SCCB) was performed with a biopsy gun. In 17 of the patients, no surgery was performed. The results of SCCB were normal in 11 of these patients; in six patients, the lesion disappeared after SCCB. In 53 of the patients, SCCB was followed by surgical biopsy. In 48 cases (91%), the results of SCCB and surgical biopsy were concordant. Of the 45 carcinomas found at surgery, 41 (91%) were correctly diagnosed with SCCB. There were no false positive results. SCCB was nondiagnostic (no representative material sampled) in three patients (6%), and in two patients (4%) a false-negative result was obtained. The infiltrating character of the tumor was correctly diagnosed with SCCB in 80% of cases. These results confirm that this radiologic procedure is an acceptable alternative to excisional biopsy. PMID- 1584910 TI - Stereotaxic fine-needle aspiration of low-suspicion, nonpalpable breast nodules: valid alternative to follow-up mammography. AB - Seventy "low-suspicion," nonpalpable solid breast nodules were evaluated with stereotaxic fine-needle aspiration with cytologic analysis as an alternative to follow-up mammography. Sonography was performed in all cases to determine the solid nature of the nodules. Eight cysts were incorrectly classified with sonography, corresponding to atypical cysts; in such cases, however, stereotaxic fine-needle aspiration not only enabled the diagnosis, but was therapeutic as well. Fifty-eight of 70 breast aspirates (83%) yielded adequate cellular material for cytologic interpretation. A specific cytologic diagnosis was made in 52 cases (51 benign, one malignant). Insufficient cytologic material was obtained in 12 cases (17%). These results should help establish the validity of stereotaxic fine needle aspiration with cytologic analysis as an alternative to follow-up mammography in patients with low-suspicion, solid breast nodules, reducing radiation exposure, patient anxiety, unnecessary biopsies, and costs. PMID- 1584911 TI - Enlarging occult fibroadenomas. AB - From July 1, 1989, through June 30, 1991, 1,218 preoperative wire-localization breast biopsies were performed at one institution. In this group, 254 (21%) of the abnormalities were fibroadenomas, 26 of which had enlarged or developed in the interval between routine or short-interval follow-up mammography. This interval growth was noted in 21 premenopausal women and in five who were postmenopausal and receiving oral estrogen supplementation. PMID- 1584912 TI - Serum glucose: effects on tumor and normal tissue accumulation of 2-[F-18]-fluoro 2-deoxy-D-glucose in rodents with mammary carcinoma. AB - The positron-emitter-labeled glucose analogue 2-[fluorine-18]-fluoro-2-deoxy-D glucose (FDG) accumulates into many cancers after intravenous injection, but the effect of serum glucose levels on FDG uptake in the tumor has not been extensively studied. In vitro, elevated media glucose levels markedly diminished FDG and FDG 6-phosphate uptake and retention in human adenocarcinoma cells, while insulin had no effect. Mammary cancers were established subcutaneously in 12 rats. Six control rats with mammary tumors were fasted overnight. Hyperglycemia was established in six rats by means of continuous glucose infusion (glucose clamp). All animals were then intravenously administered 50 microCi of FDG. Serum glucose levels were 87 mg/dL (4.83 mmol/L) in the control animals and more than 900 mg/dL (49.9 mmol/L) in the hyperglycemic animals. One hour after injection of FDG, mean F-18 uptake in the tumor, brain, small bowel, and ovaries was 2.7-9.7 times lower in the hyperglycemic animals (P less than .02). Mean F-18 activity in the kidneys tended to be somewhat higher in the hyperglycemic animals. FDG uptake in other tissues was comparable between the control and hyperglycemic groups. These data suggest that high serum glucose levels may substantially impair visceral tumor imaging with FDG positron emission tomography. PMID- 1584913 TI - Angiosarcoma of the breast. AB - Review of medical records revealed 29 women with biopsy-proved mammary angiosarcoma evaluated at the authors' institution from 1966 to 1991. The women ranged in age from 20 to 70 years (mean, 42 years). All presented with a palpable mass. Five of 29 (17%) had overlying bluish skin discoloration. Mammographic findings, available in 21 cases, included solitary uncalcified mass in 11 (52%) patients, mass with calcifications in two (10%), mass with associated skin thickening in one (5%), and no findings in seven (33%). Ultrasound, performed in five cases, revealed a solitary solid mass in three patients, multiple solid masses in one, and no findings in one. In the only case in which it was performed, magnetic resonance imaging revealed a mass with low signal intensity on T1-weighted images but higher signal intensity on T2-weighted images. Patients with higher-grade lesions at pathologic evaluation were significantly (P less than .05) more likely to have abnormal mammograms and to develop recurrent disease. PMID- 1584914 TI - Acute effects of increased intravascular volume and hypoxia on the pulmonary circulation: assessment with high-resolution CT. AB - High-resolution computed tomography (HRCT) was used to evaluate acute morphologic changes in the circulation of anesthetized miniature pigs (a) after volume loading and (b) after induction of hypoxia. Before and after each challenge, serial HRCT scans were obtained at a constant position in the caudal lobes of the lung. Scans were digitized and analyzed to determine the extent of changes in the cross-sectional area of vessels greater than 300 microns in diameter. Parenchymal background attenuation in anterior, middle, and posterior lung regions was used to assess volume changes in vessels less than 300 microns in diameter. Volume loading increased cross-sectional area by 25.2% +/- 4.3 in arteries and by 37.8% +/- 6.1 in veins and caused a gravity-dependent increase in parenchymal attenuation. Hypoxia decreased parenchymal attenuation, which was consistent with constriction of vessels smaller than 300 microns. Larger arteries and veins reacted heterogeneously. Vascular dilation during volume loading was predominantly passive, and hypoxia increased vascular tone throughout the circulation. HRCT represents a new in vivo approach to investigate vascular responses to various stimuli. PMID- 1584915 TI - Spiral CT of the thorax with reduced volume of contrast material: a comparative study. AB - The effectiveness of spiral computed tomography (CT) of the thorax performed with 60 mL of 60% contrast material was compared with that of conventional dynamic incremental CT performed with 120 mL of 60% contrast material. Fifty patients in whom contrast material-enhanced thoracic CT examination was necessary were assigned to undergo either spiral CT or dynamic incremental CT. Vascular opacification and mediastinal-lung image quality were graded independently by two observers. Vascular opacification and lung image quality were better with spiral CT than with conventional CT. Results of this pilot study encourage the use of spiral CT to decrease the volume of contrast medium used in patients undergoing thoracic CT. PMID- 1584916 TI - Contrast-enhanced MR imaging of the lung: assessments of ventilation and perfusion. AB - The use of aerosolized gadopentetate dimeglumine to define regional lung ventilation and of intravenously administered polylysine-(gadopentetate dimeglumine)40 to assess regional lung perfusion was investigated. In 10 healthy rats who breathed aerosolized gadopentetate dimeglumine (0.25 mol/L) for 5 minutes, pulmonary signal intensity increased diffusely in both lungs by more than 70%. When the same animals received intravenously administered polylysine (gadopentetate dimeglumine)40 (0.1 mmol of gadolinium per kilogram), there was an additional 300% enhancement of the pulmonary parenchyma. In a rat model of acute unilateral pulmonary embolism (n = 5), perfusion defects were identified after administration of polylysine-(gadopentetate dimeglumine)40, but no ventilation abnormality was seen after inhalation of gadopentetate dimeglumine. In a rat model of acute unilateral airway obstruction (n = 5), only the ventilated right lung enhanced after inhalation of gadopentetate dimeglumine. In four of these animals, the focal ventilation defect was accompanied by a matched decrease in perfusion, seen after enhancement of the blood pool with polylysine (gadopentetate dimeglumine)40. PMID- 1584917 TI - MR imaging of lung parenchyma: a solution to susceptibility. AB - The authors have developed a pulse sequence for imaging lung parenchyma with projection reconstruction magnetic resonance (MR) imaging that reduces the effects of motion and susceptibility. In this study, the projection reconstruction technique was further modified by optimizing MR signal frequencies for reconstructing the images. This was done by means of one of two methods. With the first method, a susceptibility map was derived from the raw image data and this map was used to indicate the optimal frequencies for reconstructing the images. The second method of susceptibility correction was a postprocessing technique in which the optimal reconstruction frequencies were selected with use of specific focusing criteria to generate the least blurred image. The effect of using susceptibility map correction on a phantom was demonstrated, and both of these methods were used to improve the visibility of pulmonary structures on images of subjects with normal and abnormal lungs. PMID- 1584918 TI - Prevalence of cystic fibrosis in fetuses with dilated bowel. AB - The authors reviewed the ultrasonographic images and medical records of 15 consecutive fetuses with dilated loops of bowel distal to the duodenum and determined the prevalence of cystic fibrosis among them. The criteria for dilated bowel loops included both subjective criteria and luminal measurements. Five of the fetuses (33%) had cystic fibrosis. Eleven had bowel obstruction at birth, and four of those 11 (36%) also had cystic fibrosis. One of the four fetuses without bowel obstruction at birth had cystic fibrosis. There were no differences in sonographic findings between fetuses with and without cystic fibrosis, except that one third-trimester fetus with cystic fibrosis had echogenic small bowel with shadowing. All of the fetuses with dilated bowel loops persisting at birth required surgery. Further studies are indicated to determine the exact risk of cystic fibrosis in this population. PMID- 1584919 TI - Pneumatic reduction of intussusception: 5-year experience. AB - Pneumatic reduction of 246 intussusceptions was attempted in 219 patients over a 5-year period. The mean age of the patients was 15.4 months. Successful reduction was achieved in 199 cases (80.9%). Bowel perforation occurred in seven cases (2.8%), requiring needle decompression of tension pneumoperitoneum in one case. Recurrence of intussusception occurred in 27 cases (11%). The mean fluoroscopy time was 3.5 minutes +/- 0.2 in successful reductions and 9.3 minutes +/- 0.9 in failed reductions (P less than .001). Logistic regression analysis helped identify four independent predictors of failure, as follows: (a) ileoileocolic intussusception (P less than .001), (b) long duration of symptoms (P less than .001), (c) rectal bleeding (P less than .01), and (d) failed reduction with barium at another institution (P less than .05). Predictors of bowel perforation were a younger age (P less than .05) and long duration of symptoms (P less than .05). Surgery was performed in 48 cases (19.5%), 16 of which required bowel resection. Transmural necrosis of bowel wall was found in nine specimens. The most important predictor of outcome in this series was a long duration of symptoms. Pneumatic reduction is a useful substitute for barium in the management of pediatric intussusception. PMID- 1584920 TI - Periportal low attenuation at CT in childhood. AB - Periportal low attenuation, defined as a low-attenuation rim around the portal vein and its branches that is seen on contrast material-enhanced computed tomographic (CT) scans, has been described in a variety of conditions in adults. The authors reviewed the appearance of periportal low attenuation on CT scans of 30 children. An association was found between a rim of low attenuation and hepatic trauma, hepatic transplantation, malignancy (undifferentiated hepatoblastoma, juvenile chronic myelogenous leukemia), and generalized hepatic disorders (acute hepatitis and congenital hepatic fibrosis). The possible mechanisms for development of periportal low attenuation include periportal tracking of blood, obstructive lymphedema, tumor infiltration, perivascular inflammation, or bile duct proliferation. PMID- 1584921 TI - Pediatric blunt abdominal trauma: periportal tracking at CT. AB - Periportal zones of decreased attenuation at computed tomography (CT) have been described in a variety of disorders. In the setting of blunt abdominal trauma, the zones have been attributed to dissection of blood along the portal tracts. Because of the observation of isolated periportal tracking (PPT) in children after blunt trauma, the authors retrospectively reviewed CT scans of the abdomen obtained in 114 children to determine the frequency of PPT, liver injury, and peritoneal fluid. PPT was present in 22% of patients (25 of 114); it was associated with liver injury in 10 and was the only liver abnormality in 15. Pathologic correlation was available in two patients: In one it revealed marked periportal lymphedema and in the other, PPT of blood. This study indicates that both hemorrhage and lymphatic edema may be represented as PPT in children after blunt abdominal injury. PMID- 1584922 TI - Superior mesenteric vascular anatomy at US in patients with surgically proved malrotation of the midgut. AB - The purpose of this study was to determine the frequency with which inversion of the superior mesenteric artery (SMA) and superior mesenteric vein (SMV) is seen at ultrasound (US) in children with malrotation. Nine patients with malrotation at upper gastrointestinal (UGI) radiographic examination (surgically confirmed) were studied prospectively. Anatomic relationships between the SMA and SMV were evaluated with real-time US in an axial projection, with the transducer placed at the midline of the anterior abdomen. Use of duplex imaging confirmed which vessel was the artery and which was the vein. Vessels were considered to be inverted if the SMV was left of the left lateral margin of the SMA. The SMA and SMV were inverted in six patients (67%) and were normal in three (33%). One patient with normal mesenteric vessels had midgut volvulus; duodenojejunal resection was required. Inversion of the SMA and SMV at US is not sufficiently sensitive to screen patients for malrotation. UGI examination remains the standard modality to diagnose this disorder. PMID- 1584923 TI - Alzheimer dementia: quantification of energy metabolism and mobile phosphoesters with P-31 NMR spectroscopy. AB - To determine whether high-energy phosphate metabolism and mobile phosphoester indexes of membrane metabolism are altered in Alzheimer disease and to help resolve some inconsistencies in the literature, brain phosphate metabolite concentrations and ratios were measured in 11 patients with mild to severe dementia of the probable Alzheimer type and 14 healthy subjects. Fully relaxed, spatially localized, phosphorus-31 nuclear magnetic resonance (NMR) spectroscopy and proton (hydrogen-1) MR imaging were performed. No significant differences were found in the concentrations and relative ratios of phosphocreatine, nucleoside triphosphate, inorganic phosphate, phosphomonoester, and phosphodiesters in whole axial sections through the lateral cerebral ventricles of the brain that could not be accounted for by atrophy. There was no correlation between P-31 NMR indexes and the severity of dementia as assessed with neuropsychologic testing. High-energy phosphate and membrane metabolism, as detected in vivo with P-31 NMR spectroscopy in whole-brain sections, do not appear to play a major role in the disease process, except as a direct consequence of atrophy quantified with H-1 MR imaging. PMID- 1584924 TI - Human brain tumors: spectral patterns detected with localized H-1 MR spectroscopy. AB - Image-guided localized proton magnetic resonance (MR) spectroscopy of intracranial tumors was performed to correlate spectral patterns and histologic findings. Thirty-six patients were examined prior to any specific treatment. Evaluation based on signal intensity ratios showed that all tumor spectra differed from spectra of healthy brain tissue. Ratios of creatine to choline containing compounds (Cr/Cho) and nitrogen acetyl-aspartate to Cho (NAA/Cho) were reduced significantly in all tumor spectra compared with spectra of normal tissue in contralateral brain hemispheres (P less than .005). Noncerebral tumors typically showed a vanishing or missing NAA signal, strongly reduced Cr signal, and additional signals, assigned to alanine in meningiomas and lipids in metastases. In contrast, 11 gliomas of grades 2 and 3 exhibited NAA/Cho ratios and Cr/Cho ratios that were less than normal but that were significantly larger (P less than .01) than corresponding values in eight meningiomas. Ten glioblastomas displayed spectra with various signal ratios, so no significant differences between them and other tumor types could be established. In nine gliomas a clearly detectable lactate signal was present. However, no direct correlation between lactate level and histologic tumor grading was found. PMID- 1584925 TI - Human brain infarction: proton MR spectroscopy. AB - Two-dimensional proton magnetic resonance (MR) spectroscopic imaging studies were performed of the distributions of the major hydrogen-1 metabolites of choline, creatine, N-acetyl aspartate (NAA) and lactate in normal (n = 6) and subacutely to chronically infarcted (n = 10) human brain. The two dimensions of phase encoding were applied over a 20-mm-thick section of brain tissue that had been selected with a double spin-echo localization method. Normal brain showed bilaterally symmetric metabolite distributions and no detectable lactate. Nine of 10 studies of brain infarction showed substantial decreases in NAA, creatine, and choline in the infarcted area compared with control areas; averaged for all studies, the decreases were 77% +/- 8, 63% +/- 11, and 54% +/- 12, respectively (mean +/- standard error). The decreased metabolite concentrations are probably due primarily to diminished cell density in the infarct. The decrease in NAA was larger than the decreases in choline and creatine. Findings in all of the studies showed lactate in the infarcted tissue and/or ventricles. The continued presence of lactate in the infarct indicates increased anaerobic glycolysis due to ischemia or other factors. PMID- 1584926 TI - Clinically documented hemorrhage in cerebral arteriovenous malformations: MR characteristics. AB - This study assessed the ability of magnetic resonance (MR) imaging to identify vascular characteristics of cerebral arteriovenous malformations (AVMs) which are predictive of hemorrhage. The study also evaluated the sensitivity and specificity of spin-echo (SE) and gradient-recalled-echo (GRE) imaging in the detection of prior clinical hemorrhage on the basis of location of the hemorrhage (parenchymal, intraventricular, or subarachnoid). Fifty patients with high-flow AVMs were evaluated. Twenty-four (48%) patients had prior clinical hemorrhage documented at computed tomography or MR imaging at the time of bleeding. Central venous drainage (P less than .001), central AVM location (P less than .001), and peri- or intraventricular AVM location (P less than .01) correlated positively with prior clinical hemorrhage. Intranidus aneurysms and angiomatous change could not be detected with MR. Nineteen of the 24 patients with prior hemorrhage underwent both SE and GRE imaging. Hypointensity, indicating the presence of iron from prior hemorrhage, was demonstrated in 14 of 19 T2-weighted SE images (sensitivity, 74%) and in 18 of 19 GRE images (sensitivity, 95%). No patient without a prior episode of clinical bleeding demonstrated evidence of iron deposition at MR imaging (specificity, 100%). PMID- 1584927 TI - Variance of the position of the cerebellar tonsils with age: preliminary report. AB - The position of the cerebellar tonsils relative to the foramen magnum was measured with sagittal magnetic resonance (MR) images in 221 patients aged 5 months to 89 years who were considered not to have disorders that would affect tonsillar position. All patients were grouped according to age. All measurements of the tonsils were obtained directly from the video console. Statistically significant (P less than .05) differences in tonsillar position were found between the 1st and 9th decades (P less than .001) and the 3rd and 9th decades (P less than .003) of life. An obvious trend existed: tonsillar ascent with increasing age. Therefore, the authors believe that a single reference standard that indicates the normal distance of the cerebellar tonsils from the foramen magnum is inappropriate unless age is considered. They suggest that the following distances below the foramen magnum (more than 2 standard deviations out of the normal range) be used as criteria for ectopia of the cerebellar tonsils: 1st decade of life, 6 mm; 2nd and 3rd decades, 5 mm; 4th to 8th decades, 4 mm; and 9th decade, 3 mm. PMID- 1584928 TI - Hospital and office practices of radiology groups. AB - To obtain information on the characteristics and practices of radiology groups in the United States, the American College of Radiology conducted a group practice survey in 1989; this report presents the main survey findings about the office and hospital practices of such groups. A questionnaire and one follow-up were mailed to all 2,591 radiology groups in the United States. Responses were weighted to reflect all groups. Hospital practices averaged 0.7 diagnostic radiologic procedures (including outpatient procedures) per patient day, with little variation by hospital type. Magnetic resonance (MR) imaging and angioplasty procedures were concentrated in teaching hospitals, but this was not true of other sophisticated procedures such as computed tomography and nuclear medicine. Offices averaged 15,000 diagnostic examinations annually, with less variation than expected according to group size. In both hospitals and offices, more than 90% of technologists were registered. Outsiders (most often, referring physicians and hospitals) had a financial interest in half of all offices. MR imaging and mammography grew faster than any other examinations, but only 44% of hospital practices accepted nonreferred patients for mammography. PMID- 1584929 TI - Late adverse reactions to nonionic contrast media. AB - A prospective study of late adverse reactions to nonionic contrast media was conducted in 2,382 patients who underwent computed tomography (CT). Late reactions were defined as those that occurred more than 30 minutes but within 2 days after completion of CT. The overall rate of late reactions was 8.0% (165 of 2,052 patients), which was greater than the rate of immediate reactions (3.8% [90 of 2,382 patients]). Headache and rash were the most frequent manifestations. Three patients experienced severe vomiting, heavy drowsiness, or oliguria and required medical attention. Late reactions occurred more frequently in female patients, younger adults, and patients with histories of allergic reactions. This investigation shows that although late adverse reactions to nonionic contrast agents are not life threatening, these reactions are not uncommon. It is important that radiologists recognize these late reactions. Patients and referring physicians should be informed that late reactions can occur and may require medical attention. PMID- 1584930 TI - Role of low-osmolality contrast media in thromboembolic complications: scanning electron microscopy study. AB - Numerous in vitro studies have found that clot formation may occur when blood is mixed directly with nonionic low-osmolality contrast media during angiographic procedures because of activation of hemostasis in the catheter; ionic contrast media, on the other hand, inhibit clot formation. Thirty patients were injected with low-osmolality contrast media--15 with ioxaglate, an ionic dimer, and 15 with iopamidol, a nonionic monomer. The inner wall of the angiographic catheter was studied with electron microscopy after selective catheterization of supraaortic vessels. Clot formation of various extent was observed in nine (60%) of the patients administered iopamidol. No coagulation process was found in the catheters of the patients administered ioxaglate. Results indicate that nonionic, low-osmolality contrast media may play a role in the formation of thromboembolisms. PMID- 1584931 TI - Regional heart wall motion: two-dimensional analysis and functional imaging with MR imaging. AB - Analysis of the transmural distribution or nonradial components of myocardial motion has previously been possible only with use of invasive techniques such as implantation of radiopaque markers. Magnetic tagging of the heart wall in conjunction with magnetic resonance imaging allows noninvasive regional analysis of within-wall motion, including its separation into components of rigid body motion and deformation. The results of this analysis can be displayed as functional images. This provides a new tool for the study of heart wall motion that should be of use for both basic physiologic and clinical research applications. PMID- 1584932 TI - Pulmonary hypertension: pulmonary flow quantification and flow profile analysis with velocity-encoded cine MR imaging. AB - Velocity-encoded cine magnetic resonance (MR) imaging provides two-dimensional velocity maps of a cross-sectional area of a vessel. Pulmonary flow and flow patterns in the main pulmonary artery were analyzed with velocity-encoded cine MR imaging and Doppler echocardiography in 10 patients with pulmonary hypertension (PH), one patient with a dilated main pulmonary artery, and 10 healthy subjects, and these findings were compared. Peak systolic velocity measured with velocity encoded cine MR imaging was similar to that measured with Doppler echocardiography in healthy subjects and in patients with PH. Velocity-encoded cine MR imaging demonstrated substantial differences in velocity across the vascular lumen in PH. The flow pattern in healthy subjects was different than that in patients with PH; the latter had lower peak systolic velocity and greater retrograde flow after middle to late systole. The retrograde flow observed in patients with PH reflected hemodynamic events, since it was inversely proportional to pulmonary flow volume and directly proportional to pulmonary resistance and cross-sectional area of the vessel. Velocity-encoded cine MR imaging demonstrates an inhomogeneous flow profile in PH and may serve as a noninvasive method to estimate pulmonary vascular resistance. PMID- 1584933 TI - Penetrating atherosclerotic ulcers of the descending thoracic aorta: evaluation with CT and distinction from aortic dissection. AB - Penetrating atherosclerotic ulceration of the aorta is a poorly understood entity that clinically mimics classic aortic dissection but has imaging features that are distinctly different. In a review of 16 patients with penetrating atherosclerotic ulceration, patients were typically hypertensive (n = 14), and they experienced chest or back pain (n = 13). All patients had an abnormal chest radiograph, with diffuse (n = 14) or focal (n = 2) enlargement of the descending thoracic aorta. Features at contrast material-enhanced computed tomography (CT) included intramural hematoma (n = 16), focal ulcer (n = 15), displaced intimal calcification (n = 13), pleural and/or extrapleural fluid (n = 7), mediastinal fluid (n = 4), and a thick or enhancing aortic wall (n = 6). The chest radiograph and CT findings were compared in patients treated conservatively (n = 9) and surgically (n = 7). These findings did not correlate with the need for surgery. Eight of nine conservatively treated patients were asymptomatic after treatment with antihypertensive medication. Contiguous dynamic contrast-enhanced CT of the aorta enables distinction of ulceration from dissection, which is particularly important in the hemodynamically unstable patient because the surgical management of ulceration is more extensive than that for aortic dissection. PMID- 1584934 TI - Subcutaneous seeding after percutaneous ethanol injection of liver metastasis. AB - A 72-year-old cirrhotic woman underwent percutaneous ethanol injection treatment of a liver metastasis of unknown origin. A subcutaneous metastasis developed at the site of the punctures. Needle track seeding is a rare complication of fine needle biopsy but has never--to the authors' knowledge--been reported after percutaneous ethanol injection. The possible causes of this complication are discussed. PMID- 1584935 TI - Results of radiation therapy in early glottic carcinoma: multivariate analysis of prognostic and radiation therapy variables. AB - A detailed retrospective analysis was performed with 103 patients who had T1 carcinoma of the glottic larynx and underwent radiation therapy between 1960 and 1987. Prognostic and radiation therapy variables were analyzed including sex; age; staging procedures; mucosal extent; histologic grading of tumor; field size; use of wedges; treatment of alternate fields versus both fields every day; nominal standard dose; time, dose, and fraction; dose per fraction; total radiation dose per fraction; total radiation doses; and the impact of cord stripping. Initial local control was 89%, and ultimate control after surgical salvage was 97%, with a 5- and 10-year adjusted survival of 98%. Univariate analysis indicated that larger field size (P = .04), histologic grade (P = .02), and treatment strategy (P = .08) were of some value in predicting recurrence. Multivariate analysis indicated that field size (P = .03) was the only significant variable in predicting local recurrence. These data confirm that radiation is highly effective in the treatment of early laryngeal cancer. PMID- 1584936 TI - Diagnosis of uterine anomalies: relative accuracy of MR imaging, endovaginal sonography, and hysterosalpingography. AB - The purpose of this study was to compare the relative accuracy of magnetic resonance (MR) imaging (n = 26), endovaginal sonography (EVS) (n = 14), and hysterosalpingography (HSG) (n = 20) in the classification of mullerian duct anomalies in 26 patients. There were 24 cases of surgically proved anomaly, and two patients had normal uteri (one with a vaginal septum). MR imaging allowed diagnosis of 24 of 24 cases (accuracy, 100%), and EVS was correct in 11 of 12 cases (accuracy, 92%). HSG was correct in only four cases. In the diagnosis of septate uterus, MR imaging demonstrated a sensitivity and specificity of 100% and EVS demonstrated a sensitivity of 100% and a specificity of 80%. Both MR imaging and EVS demonstrated a sensitivity and specificity of 100% in distinguishing those anomalies that did not require surgery. The high accuracy of MR imaging and EVS permit noninvasive differentiation of uterine anomalies and can spare women diagnostic laparoscopy, promoting cost-effective diagnosis. PMID- 1584937 TI - Renal dysfunction in hepatic disease: early identification with renal duplex Doppler US in patients who undergo liver transplantation. AB - To improve early detection of renal dysfunction in patients who undergo liver transplantation, a prospective study was performed with intrarenal duplex Doppler sonography before and after liver transplantation in 42 patients. The duplex Doppler findings were compared with multiple clinical and laboratory findings; patients were grouped on the basis of preoperative renal resistive index (RI) and serum creatinine level. The mean initial renal RI was elevated (.73 +/- .07 [standard deviation]); after transplantation, it was lower (.60 +/- .06) (P less than .001). Thirty-six patients had a normal serum creatinine level at the preoperative Doppler examination. Patients with an elevated renal RI (n = 19) had a greater chance of subsequent renal dysfunction (P less than .001), hemodialysis (P less than .01), longer stays in the intensive care unit (P less than .05), and longer hospital stays after surgery (P less than .05) than those with a normal renal RI (n = 17). In 34 patients the RI fell 10% or more after surgery and none died, whereas five of eight patients (62%) whose RI fell less than 10% died. Doppler analysis enabled identification of patients without azotemia whose course of disease before and after surgery was similar to that of patients with clinically recognized renal disease. PMID- 1584938 TI - Focal spiculation of the upper thoracic esophagus: normal variant at double contrast esophagography. AB - A review of 100 routine biphasic upper gastrointestinal examinations revealed focal spiculation of the upper thoracic esophagus as a transient finding in 11 patients (11%) who otherwise had no clinical or radiographic signs of esophageal disease. All 11 patients had remarkably similar findings, with thin (1-2 mm wide), transverse folds or striations above the level of the aortic arch, producing a spiculated or serrated appearance in profile. This focal spiculation should be considered a normal variant in the esophagus on double-contrast radiographs. It is suspected that this phenomenon is related to weakening of peristalsis or localized contraction of the longitudinally oriented muscularis mucosae at the junction of the striated- and smooth-muscle portions of the esophagus. Whatever the explanation, radiologists should be familiar with this finding, so that it is not mistaken for a focal area of esophagitis. PMID- 1584939 TI - Deglutition in elderly patients with dementia: findings of videofluorographic evaluation and impact on staging and management. AB - Oral and pharyngeal function in 131 institutionalized elderly patients with advanced dementia was evaluated by means of videofluoroscopic deglutition examination (VDE). Findings were normal in only nine (7%) patients. Oral-stage dysfunction was observed in 93 (71%) patients, pharyngeal dysfunction in 56 (43%), and pharyngoesophageal-segment abnormalities in 43 (33%). Multiple-stage dysfunction was noted in 55 (42%) patients. Major aspiration of contrast medium was present in 31 patients, and minor aspiration in 66. Evaluation of VDE findings prompted a change in clinical staging (degree of impairment) in 40 patients and substantial alteration in treatment planning in 28. At clinical bedside evaluation, the degree of bolus misdirection was overestimated in 19 patients with minor aspiration and underestimated in seven with major aspiration. Dementia is often associated with oral and pharyngeal impairment, and VDE can be important in diagnosis and treatment. PMID- 1584940 TI - Spiral CT of the pancreas. AB - Computed tomography (CT) is the modality of choice for evaluation of pancreatic disease. In this prospective study, images obtained with spiral CT, which enables examination of a region of the body in a single breath-hold, were compared with those obtained by means of dynamic CT with automatic table incrementation in two groups of 30 patients referred for suspected disease of the pancreas. In both groups, vascular opacification and anatomic detail were analyzed with a grading system (1 = poor, 2 = good, 3 = excellent). Vascular opacification received mean grades of 2.78 and 2.33 in the spiral CT and control groups, respectively. Anatomic detail received mean grades of 2.63 and 2.42 in the spiral CT and control groups, respectively. Respiratory motion artifact was absent in all spiral CT examinations but was present in 17 of 30 control CT examinations. Images obtained with spiral CT showed superior vascular opacification and reduced respiratory artifact with smaller amounts of contrast agent (90 mL vs 120 mL) compared with those obtained with dynamic CT. PMID- 1584941 TI - Uncomplicated amebic liver abscess: prospective evaluation of percutaneous therapeutic aspiration. AB - The performance of therapeutic aspiration in the treatment of amebic liver abscess, advocated and practiced in many centers, is controversial. Previously, this practice has been evaluated in retrospective analyses. To test the potential benefit of therapeutic aspiration, the authors undertook a prospective randomized trial in 57 patients admitted for suspected amebic liver abscess during a 15 month period. Sixteen patients were excluded from the trial. The remaining 41 patients were randomly included in one of two study groups to receive amebicidal therapy alone or amebicidal therapy coupled with image-guided percutaneous therapeutic aspiration. All patients in the trial recovered. No statistically significant benefit was demonstrated in the aspiration group for the two objective parameters evaluated: length of hospitalization and duration of time to becoming afebrile. Subjective improvement in symptoms after aspiration was greater in the aspiration group at a marginally statistically significant level. These data do not support the adjunctive performance of percutaneous therapeutic aspiration in the treatment of uncomplicated amebic liver abscess. Amebicidals alone were equally efficacious in treating the group studied. PMID- 1584942 TI - Appendiceal US scans: histologic correlation. AB - High-resolution in vitro ultrasonography (US) of 20 surgical appendiceal specimens was performed to compare appearances of appendiceal tissue at US with corresponding histologic features. With an articulated-arm system and micropositioner, precise spatial correlation was achieved. As elsewhere in the gastrointestinal tract, five distinct echo layers were observed. Normal and inflamed specimens demonstrated these layers, but the architecture became disorganized and indistinct in cases of appendicitis. Three measurements were made for each specimen: (a) overall cross-sectional diameter, including the lumen, (b) thickness of the submucosal echo layer, and (c) the combined thickness of both walls, excluding the lumen. For the inflamed specimens, a substantial increase in the thickness of the summed wall measurements was found. Wall US appearance alone may be misleading in differentiation of normal and abnormal appendices. PMID- 1584943 TI - Occult fracture patterns of the knee associated with anterior cruciate ligament tears: assessment with MR imaging. AB - One hundred consecutive magnetic resonance (MR) images of the knee in patients with acute complete anterior cruciate ligament (ACL) tears were reviewed to evaluate the prevalence and patterns of associated occult fractures. Eighty-nine occult fractures were identified in 56 knees. All occult fractures were in the posterior aspect of the lateral tibial plateau. Of these, occult fractures were isolated in 24 cases (43%) and were in combination with fractures in the middle aspect of the lateral femoral condyle in 26 (46%), with fractures in the posterior aspect of the medial tibial plateau in four (7%), and with fractures involving all three areas in one (2%). Disruption of the ACL under valgus stress leads to anterior translation of the tibia and relative external rotation of the femur. This allows impaction of the posterior portion of the lateral tibial plateau against the middle of the lateral femoral condyle and accounts for the unique pattern of occult fractures associated with ACL tears. An occult fracture of the posterior lateral tibial plateau with or without an associated fracture in the lateral femoral condyle ("kissing contusion") is a relatively frequent finding in acute ACL tears and, when present, is highly suggestive of such an associated tear. PMID- 1584944 TI - Three-dimensional gradient-echo MR imaging of the knee: comparison with arthroscopy in 100 patients. AB - To compare the findings on magnetic resonance (MR) images of the knee obtained with a three-dimensional gradient-echo (GRE) sequence with findings at arthroscopy, the menisci, cruciate ligaments, and hyaline cartilage were assessed in 100 patients. At MR imaging (performed by means of fast imaging with steady state precession) and arthroscopy, the menisci (n = 200) and areas of hyaline cartilage (n = 500) were assigned grades of zero (normal) to three (greatest abnormality). The cruciate ligaments were considered intact, partially torn, or completely torn. The sensitivity of MR imaging in diagnosis of meniscal tears seen at arthroscopy was 97% and the specificity, 94%. For complete tears of the anterior cruciate ligament, the sensitivity was 92% and specificity, 96%. In the posterior cruciate ligament, both the sensitivity and specificity were 100%. Good correlation existed between findings at MR imaging and those at arthroscopy in assessment of focal thinning and full-thickness loss of hyaline cartilage, but arthroscopy enabled superior visualization of minor fissuring. Three-dimensional GRE MR imaging enables accurate assessment of the articular cartilage of the knee. The evaluation of meniscal tears and the cruciate ligaments has a high negative predictive value. PMID- 1584945 TI - Soft-tissue sarcomas: use of textural patterns in skeletal muscle as a diagnostic feature in postoperative MR imaging. AB - The authors assessed the value of tissue textural patterns as a diagnostic feature for differentiating nonspecific posttreatment tissue changes from musculoskeletal sarcoma recurrence on magnetic resonance (MR) images. The MR imaging studies of 40 patients who had previously undergone surgery and radiation therapy for soft-tissue sarcomas of the lower extremities were evaluated in a blind fashion. In 31 of the MR imaging studies, T2-weighted images demonstrated diffuse areas of high signal intensity in soft tissues at the operative region. Close examination of the corresponding regions on high-resolution transverse T1 weighted images demonstrated textural features typical of skeletal muscle in 23 patients and the absence of such features in eight. None of the 23 patients with the "texture sign" proved to have macroscopic tumor recurrence at clinical or surgical follow-up. Among the eight patients without recognizable textural features of muscle in the regions suspicious for tumor recurrence, two proved to have recurrent tumor at surgery. Recognition of a texture sign on high-resolution T1-weighted spin-echo images of regions suggestive of tumor recurrence helps improve the diagnostic specificity of follow-up MR examinations in patients who have undergone treatment for soft-tissue sarcomas. PMID- 1584946 TI - Influence of calibration materials in single- and dual-energy quantitative CT. AB - With single-energy (SE) quantitative computed tomography (CT), the density of bone mineral in the vertebral body can be estimated. With dual-energy (DE) quantitative CT, both bone-mineral density and fat content can be measured. The calibration device normally used contains materials mimicking trabecular bone, fat, and hematopoietic tissue. To evaluate the influence of different calibration materials on these estimates, theoretical CT numbers were calculated for the trabecular part of the vertebral body and for different calibration devices. Calibration devices were simulated; they contained either identical materials or various accepted tissue-mimicking materials. For all combinations, quantitative CT data were generated for the SE quantitative CT method and for two DE quantitative CT methods. Only one method provided accurate results under ideal circumstances. The selection of tissue-mimicking materials in the calibration devices is important for the interpretation of results of SE and DE quantitative CT. Errors of more than a factor 2 were found when different types of materials were used. PMID- 1584947 TI - Measurement of scatter fractions in clinical bedside radiography. AB - The authors present measurements of scatter fraction (SF), the ratio of scattered to total imaged photons, from clinical bedside radiographs of 102 patients. These measurements were obtained by using a new posterior beam-stop technique that does not alter the diagnostic image but that simultaneously provides SF measurements at 224 locations in the image. The SF values in the lung were found to be consistent with previous measurements, while the SF values in the mediastinal and retrocardiac areas were larger than previously reported. SFs in diseased lung were significantly larger than SFs in normal lung. The range of SF values was large for all anatomic locations. For applications in which accurate scatter estimation is required, this wide range of values suggests that SFs should be measured in each individual image. PMID- 1584948 TI - Binary screen detector system for single-pulse dual-energy radiography. AB - Dual-energy radiographic acquisition performed with a single pulse of x rays has been limited to use of stacked detectors such as photo-stimulable phosphor plates. In this study, a binary screen system is introduced that enables single pulse dual-energy acquisition with nonstacked detectors such as charge-coupled devices (CCDs). Two x-ray phosphors with different K edges, designed to emit light of different wavelengths, were bound together in a single screen. Two CCD cameras, each sensitive to the respective wavelengths emitted by each phosphor, are proposed to be coupled to the binary screen. Optical isolation and detection of the optical emissions from the screen would enable simultaneous acquisition of both low- and high-energy images, which can then be used in dual-energy subtraction. Computer simulation results and experimentally acquired images suggest that the binary screen approach may be a viable alternative to stacked detector technology for dual-energy radiographic imaging. PMID- 1584949 TI - Superelastic guide-wire snare for removal of foreign bodies from the urinary tract. AB - A superelastic guide wire was used (after failure of other methods) as a loop snare to retrieve a foreign body from the ureter in three patients. In vitro comparison of the expansion capability of the superelastic guide wire and that of the standard retrieval wire showed that the superelastic wire forms larger loops within an elastic space. Also, because of less frictional resistance and its ability to be formed into stiffer loops, the superelastic wire resists kinking and is easier to manipulate than the standard wire. PMID- 1584950 TI - Periosteal new bone of ribs with associated extremity fractures after high frequency jet ventilation. PMID- 1584951 TI - Pseudomass at CT and MR imaging. PMID- 1584952 TI - Quantitative analysis of brain tissue volumes with MR imaging. PMID- 1584953 TI - System for transmitting images. PMID- 1584954 TI - Neurologic complications of petrosal sinus sampling. PMID- 1584955 TI - Neuropathology and pathogenesis of HIV encephalopathies. AB - The nervous system is frequently affected in patients with the acquired immune deficiency syndrome (AIDS). In addition to opportunistic CNS infections and cerebral lymphomas, approx. 20% of the patients develop HIV-associated encephalopathies. Two major histopathological manifestations are observed. HIV leukoencephalopathy (progressive diffuse leukoencephalopathy) is characterized by a diffuse loss of myelin in the deep white matter of the cerebral and cerebellar hemispheres, with scattered multinucleated giant cells and microglia but scarce or absent inflammatory reaction. HIV encephalitis (multinucleated giant cell encephalitis) is associated with accumulations of multinucleated giant cells, inflammatory reaction and often focal necroses. In some patients, both patterns may overlap. In order to identify the HIV genome in the CNS, brain tissue from 27 patients was analyzed for the presence of HIV gag sequences using the polymerase chain reaction (PCR) and primers encoding a 109 base pair segment of the gag gene. Amplification of HIV gag succeeded in all 5 patients with clinical and histopathological evidence for HIV encephalopathy but was negative in the 20 AIDS patients with opportunistic bacterial, parasitic and/or viral infections or with cerebral lymphomas. These results strongly suggest that the evolution of histopathologically recognizable HIV-encephalopathies closely correlates with the presence and/or tissue concentration of HIV. Since there were no cases with amplified HIV DNA in the absence of HIV-associated tissue lesions, we conclude that harboring and replication of HIV in the CNS rapidly causes corresponding clinical and morphological changes of HIV-associated encephalopathies. In two children with severe HIV encephalomyelitis, large amounts of HIV gag and env transcripts were detected in affected areas of the brain and spinal cord by in situ hybridization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584956 TI - In situ hybridization histochemistry in the diagnosis of viral infections of the central nervous system. AB - In situ hybridization histochemistry opened new perspectives for the study of viral infections of the central nervous system. Immunohistochemistry can give information about the presence of a viral infection only, if the specific viral proteins are expressed in the infected cells, while in situ hybridization can detect viral genes also in case of a latent, non-productive infection. The basic technique has to be modified according to the kind of viral nucleic acid to be displayed (genomic DNA, plus or minus strand genomic RNA, viral mRNA). For detection, the highly sensitive radioactive or the less sensitive non-radioactive (enzyme-) labels can be applied. For the determination of the cell type harbouring the virus and for correlation of viral nucleic acids with viral proteins, in situ hybridization techniques and immunohistochemistry have to be combined. PMID- 1584957 TI - [Multi-infarct and Alzheimer dementia--problems of differential diagnosis]. AB - The differential diagnosis of Alzheimer's and so-called multi-infarct dementia is still a major problem in clinical dementia research. It was Binswanger who in 1894 pointed out that a subtype of vascular dementia exists which is characterized by subcortical arteriosclerotic encephalopathy. It is this type that can most easily be mistaken for Alzheimer's dementia, presented for the first time in 1906, which may be associated with congophilic angiopathy leading to brain infarction. Beyond clinical criteria, which in part are summarized in Hachinski's ischemic score, further advancement of brain imaging techniques, especially those yielding perfusion or metabolic data, has facilitated and substantiated clinical in vivo distinction. PMID- 1584958 TI - Combined erbB gene overexpression and decreased H-ras gene expression in human gliomas. AB - The expression of 15 oncogenes including erbB and H-ras in 18 human glial tumors 10 glioblastomas, 1 astrocytoma grade III-IV, 2 oligodendrogliomas grade III, 2 astrocytomas grade II-III, 1 astrocytoma grade II, 1 oligodendroglioma grade II and 1 oligoastrocytoma grade II--was determined by hybridizing RNA against oncogene probes using the Dot Blot technique. Compared with bovine cerebrum (control), the oncogenes abl, erbA, fms, fos, K-ras, mil, mos, myb, rel, sis, src and yes were expressed equally in both bovine cerebrum and the gliomas. However, the expression of erbB was increased 2-9-fold in all except one glioma, and the expression of H-ras was decreased by the factor 0.3-0.7 in 15 tumors. No obvious correlation was found between tumor histology and changed expression of erbB and/or H-ras or between the grade of malignancy and the expression of any oncogene tested. A connection between erbB and H-ras has been shown by several studies. Our results confirm the relationship between H-ras and erbB. However, the meaning of the H-ras decrease in combination with the erbB elevation has to be clarified. PMID- 1584959 TI - [Expression of immunohistochemical differentiation markers in normal and transformed neoplastic neuroectodermal stem cells]. AB - The cells of primitive neuroectodermal tumours may undergo differentiation and, eventually, may be transformed to neurons, glial cells, and ependymal cells. Early stages of neuroectodermal differentiation may primarily be determined by means of immunohistochemical methods. Immunohistochemical investigations were performed on brains of human foetuses obtained from the 18th to 36th weeks of pregnancy, with a view to elucidating the process of maturation during foetal development and to determining the antigens identifiable in cells in the course of differentiation, following fixation in formalin and embedding in paraffin. Gliafibrillar acid protein (GFAP) and vimentin proved to be of particularly high stability and, consequently, were easily detectable from paraffin material. The same antigens were focally recordable also from eight of 17 primitive neuroectodermal tumours. Clues were rare in these tumours as to neuronal differentiation. This was attributed to instability of neurofilament proteins under conditions of formalin fixation and paraffin embedding. PMID- 1584960 TI - Activity of ornithine decarboxylase (ODC) and polyamine levels as biochemical markers of malignancy in human brain tumors. AB - The content of the polyamines putrescine, spermidine and spermine, and the activity of their metabolic key enzyme ornithine decarboxylase (ODC) were measured in tissue samples obtained during operation of 45 patients with primary or recurrent gliomas, meningiomas and pituitary adenomas. Biochemical analysis and histopathological classification were carried out in the same tumor samples. In benign tumors ODC activity was less than 10 nmol/g/h, whereas in malignant gliomas values up to 34 nmol/g/h were observed. In rapidly growing tumors pronounced heterogeneity was observed with high values in solid tumor parts and low values in necrotic areas. Thus, high ODC activity represents a reliable biochemical marker of malignancy in brain tumors, but low values do not prove benignity. PMID- 1584961 TI - [DNA synthesis activity and growth fractions of brain tumors]. AB - Histoautoradiographic and immunohistochemical studies of biopsies from 27 brain tumors yielded the following preliminary conclusions: 3H-thymidine labeling indices and Ki-67 growth fraction indicate the proliferative activity more reliable than counting of mitoses, the fraction of DNA synthesizing tumor cells and the Ki-67 growth fraction show an equal behaviour, as expected, the immunohistochemical values are higher than the labeling indices because all tumor cells within the proliferation cycles express the nuclear antigen. By the increase of the number of tumors and the use of the different cell kinetic methods on the same tumor tissue the prerequisite to grading of brain tumors as a basis of therapeutic strategy can be improved. PMID- 1584962 TI - Application of the AgNOR technique to neurooncology. AB - The silver staining of interphase nucleolar organizer regions (NORs) is a recently developed method to measure cell proliferation in tissue specimens. The major silver staining protein is nucleolin, a 92 kd nucleolar protein, which probably controls rDNA transcription. Nucleolin itself is under control of p34cdc2 kinase, which is a subunit of M phase kinase. The specific silver staining of NORs measures ribosomal gene activity and is therefore useful in measuring cell proliferation via nucleolar biosynthetic activity. Although human tumors of different malignancy grades usually can be distinguished by their AgNOR number, there is considerable overlap between different grades which significantly hampers their use in individual cases. For routine application of the AgNOR technique in histopathology we propose a standardised staining protocol with use of internal control cells and the use of image analysis for AgNOR enumeration. PMID- 1584963 TI - [AgNOR in neurooncology]. AB - By means of a standardized silver staining technique, nucleolar organizer region associated proteins (AgNORs) have been demonstrated in paraffin sections of 41 astrocytomas and glioblastomas and 19 meningiomas. Computer-assisted image analysis was used to measure AgNORs together with other nuclear features. Significant differences in number and configuration of AgNORs have been found between non-anaplastic astrocytomas and anaplastic gliomata. In meningiomas, tumours with signs of increased proliferative activity and usual non-anaplastic ones could be discriminated using AgNOR data. PMID- 1584964 TI - [Preoperative computer tomography and postoperative classification of brain tumors]. AB - Imaging of different brain tumor types by computed tomography (CT) or contrast enhanced CT scans is often very similar. Therefore, the exact preoperative CT diagnosis of intracranial neoplasms is difficult. Among 100 cases (88 primary brain tumors, 12 brain metastases), the preoperative classification by CT was correct in 51 and partially correct in 22 cases. A corresponding presumptive CT diagnosis was made in 22 brain neoplasms. 5 cases were misinterpreted. Examples of CT scans and histological pictures are compared and analysed according to the literature. PMID- 1584965 TI - Lysosomal proteinases as putative diagnostic tools in human neuropathology: Alzheimer disease (AD) and schizophrenia. AB - The cathepsin B, D and L were studied by immunohistochemical techniques in the human postmortem brain. The enzyme were primarily localized in neurons. Makroglial cells were seldom immunostained. It is shown that cathepsins B and D frequently occur in neuritic plaques of Alzheimer victims, thereby raising the question, whether or not cathepsin immunohistochemistry is a useful tool in the diagnosis of this disease. Furthermore, we identified certain glial cells to be immunoreactive for cathepsins in schizophrenics. PMID- 1584966 TI - [The morphology of hemostasis failure in gliosal brain tumors]. AB - A retrospective study was conducted into 37 brains of patients, who had died of Grade 2-4 glioma. For assessment of morphological signs of hemorheological failure, microcirculation was checked by H & E, Kluver-Barrera, and Goldner staining as well as by staining for fibrin, using a modified technique according to Zerbino and Lukasewitsh. Microthrombosis was recorded from 30 in the above 37 brains, all of them related to patients with Grade 3 glioma and glioblastoma. Fibrin thrombi represented the predominant variant of microthrombosis. They exhibited differentiated characteristics depending on their localisation in the central and the peripheral regions of the tumour or in surrounding brain tissue. Also included in the study were rates of vascular proliferation and types of necrosis as well as relations between these and microthrombi. The role played by microthrombi in such cases of glial tumours is discussed in some detail. PMID- 1584967 TI - [Primary malignant melanoma of the central nervous system]. AB - Obduction of a woman aged 52 years, showed a diffuse primary leptomeningeal melanoblastosis with development of a malignant melanoma in adjacent region of brain parenchyma. Clinically it was misdiagnosed as a haematoma. PMID- 1584968 TI - [Central nervous findings in neurofibromatosis]. AB - Neurofibromatosis (NF) is subdivided into at least two different forms: NF-1, which is characterized by cafe-au-lait spots, cutaneous neurofibromas, Lisch nodules and osseous dysplasias, and NF-2, the hallmarks of which are bilateral acoustic neuromas. Neuropathological findings in 5 cases of NF-1 and 3 cases of NF-2 are presented. PMID- 1584969 TI - [Apparent contradictory findings in the immunohistochemical detection of hormone production in hypophyseal adenoma]. AB - In some cases of pituitary adenomas, the immunohistochemical proof of a hormone production does not correspond with the clinical findings. False negative results are caused by different functional stages of the adenoma cells when hormone granules are largely released. Then, the intracellular content of hormone granules lies under the immunohistochemical demonstrability although clinical findings show high serum values of the hormone in question. Especially in prolactinomas, sparsely granulated forms are not rare. In these cases, the proof of a hormone production is possible by means of immuno-electronmicroscopy. Preoperative application of a bromocriptine therapy may falsify the results too. False positive results may occur in "plurihormonal" adenomas. True plurihormonal adenomas--especially the combinations GH/PRL and FSH/LH--exist but frequently reported combinations of several hormones should be seen with care. Often, the operatively removed tissue is cut into small pieces not only containing adenomatous tissue but also parts of the neighbouring normal pituitary gland with a production of several or even all hormones investigated. By use of GFAP or S 100 protein for the detection of folliculostellate cells, adenomatous and normal pituitary tissue can be differed. Folliculostellate cells can only be found in normal pituitary but not in adenomas. PMID- 1584970 TI - Morphological and functional characterization of cell cultures from adult human adenohypophyses. AB - Parallel primary cultures have been prepared from dispersed cells of adult human pituitary anterior lobes and can be used as a model system for cell-biological studies. The cultured cells were able to secrete all the known hormones of the adenohypophysis. Bromocriptine administration markedly reduced prolactin release into the medium while slightly enhanced growth hormone release. The adequate response of somatotrophs to GRF and SRIF could not be demonstrated. PMID- 1584971 TI - Ornithine decarboxylase in normal and disturbed brain development. PMID- 1584972 TI - Characterization of astroglial cell proliferation in vitro and in vivo. AB - On the basis of experimental set-ups in vitro and in vivo and by making use of specific autoradiographical techniques, the following data on the proliferation of astrocytes from newborn rats in vitro and unpretreated rats and mice in vivo could be obtained: (i) The commonly employed immunohistochemical staining techniques in vitro are not applicable in tissue sections. (ii) In vivo, astrocytes show increasing durations of cell cycle (tc) as well as S phase (ts) prenatally until about birth. A similar trend can be observed in vitro. However, the absolute values for ts and tc can be substantially modified depending on the culture conditions. (iii) As regards the mode of proliferation, astrocytes in vitro grow exponentially and without transition of quiescent cells from the non growth fraction into the growth fraction (GF). In contrast, astrocytes in vivo exhibit steady-state growth and continuous recruitment of proliferating cells from the non-GF. These differences show that there is a need for further in vivo experiments when studying new strategies in the treatment of gliomas. PMID- 1584973 TI - [The dopamine agonist, lisuride, in the therapy of Parkinson disease]. AB - The development of fluctuations in disability are a main problem of the levodopa long-term treatment in Parkinson's disease. The early combination of low doses of levodopa with a dopamine agonist as lisuride improves the symptoms of Parkinson's disease as much as a monotherapy but prevents the development of fluctuations in disability and dyskinesias at the same time. PMID- 1584974 TI - [Lissencephaly--the spectrum of pathomorphologic findings]. AB - The autopsy findings in 3 cases of type I ("classical") and 3 of type II ("hydrocephalic") lissencephaly are presented. The characteristic pathomorphology is described and some aspects about pathogenesis are considered. PMID- 1584975 TI - Fluorescent latex microspheres for retrograde tracing of neurons in mouse basal forebrain combined with immunocytochemistry: a methodical approach. AB - The presented methodical contribution demonstrates the suitability of rhodamine labelled latex microspheres with a defined mean diameter of around 20 nm for retrograde neuronal tracing. After small injections of about 200 nl red fluorescent tracer into visual cortex of mice afferent neurons were labelled in cortical and subcortical structures. Basal forebrain neurons containing the tracer were further characterized by the concurrent visualization of choline acetyltransferase, a marker for cholinergic neurons, and parvalbumin, a putative marker of GABAergic neurons, by immunofluorescence. PMID- 1584976 TI - [Dendrite-morphometry of lamina-V-pyramidal cells in premature brain damaged humans--a Golgi study]. AB - Specimens from the area 10 of the frontal cortex collected out of 7 patients with severe mental retardation, aged 3 to 24 years and also 8 non-neuropsychiatric age matched controls were processed according to the Golgi-Kopsch method. The total length of the apical side-dendrites and of the basal dendrites was measured on layer V pyramidal neurons. Compared with controls the total dendritic length of the apical side-dendrites as well as of the basal dendrites was significant reduced in the affected patients (p less than 0.001). The reduced dendritic length represents perhaps a morphological correlate to the mental dysfunction. PMID- 1584977 TI - [The occurrence of aluminum-containing lysosomes in the kidney of experimentally treated rats]. AB - Aluminium was detected by electron spectroscopic imaging and electron energy loss spectra in the lysosomes of all cell types of the nephron in rats treated with aluminium chloride after 5/6 nephrectomy. The lysosomes of kidney cells of untreated rats did not demonstrate any detectable amounts of aluminium. Electron energy loss spectra showed the regular occurrence of iron (and also other elements) in the lysosomes of both groups of rats. PMID- 1584978 TI - Parvalbumin and calbindin immunoreactivity in the rat brain: a double immunolabelling method. AB - Parvalbumin and calbindin, two calcium binding proteins in the nervous system, are present in certain neuronal subpopulations. In the present study a method for a simultaneous demonstration of the both antigens was developed, which labels parvalbumin- and calbindin-containing structures in contrasting colours. A horseradish peroxidase-conjugated second antibody was used for the visualization of the monoclonal anticalbindin antibody, whereas the biotinylated anti parvalbumin antibody was demonstrated by means of a biotin-streptavidine-alkaline phosphatase system. The method may be useful to classify neuronal populations and to study their morphological relationship. PMID- 1584979 TI - [Annotation to the mitochondrial genome]. AB - After a brief explanation of the mitochondrial function, especially in the relation to the inner-cell coordination, the study analyzed the mitochondrial hypertroph-dilatative cardiomyopathy, myopathy and scrapie which were recently tied to the "D-loop fragment" of the mtDNA. Any primary connection between viral unconventional slow infections and the mitochondrial genome seems unlikely. It is argued in the study that this category of diseases can be much better explained through the transfer of the so-called mobile retroelements. PMID- 1584980 TI - Extranucleolar genome reactivation: topochemical studies on early bovine embryo. A review. AB - A review is presented of fine-structure autoradiographic [incorporation of (5 3H)uridine] and immunoelectron microscope (localization of small nuclear ribonucleoproteins--snRNPs) data on the onset of extranucleolar transcription in early preimplantation bovine embryo. First incorporation (5-3H) uridine into blastomere nuclei nucleoplasm occurs, in the early cow embryo, during the 8-cell stage. Both the degree of chromatin condensation as well as the intensity of labeling increase as the fourth cycle of the embryonic blastomeres progress. However, neither the level of extranucleolar chromatin condensation nor the degree of labeling usually detected in somatic cells have been observed during this stage but occurred only in later stages of embryo development. The association of the label with the periphery of the condensed chromatin demonstrates, as in other cell types the sites of newly synthesized hnRNA. A further insight into the functional microarchitectural changes of the early cow embryo nuclei in relation to the onset of transcription has been obtained by immunoelectron microscope studies on Lowicryl K4M embedded material. Using this technique, the pattern of the contrast in the preparations following uranyl/lead staining was comparable to that obtained by the Bernhard's (1969) regressive staining for preferential nuclear-RNP visualization. In this way, the coordinate appearance of perichromatin fibrils on the borderline of the already condensed chromatin was evident during the 8-cell stage. Especially in the "in vitro" produced embryos the condensed chromatin occurred in marked blocks with a clearly defined perichromatin region in the thin sections. In the same nuclear area Sm antigen (associated with a group of snRNPs) has concentrated and localized to perichromatin fibrils.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1584981 TI - [An intermediate, generalized form of neuroaxonal dystrophy--light- and electron microscopic findings]. AB - This report concerns a 11-year-old girl--at the time of death--who developed normally until the age of 2 years when further psychomotoric maturation stopped and then regressed. The disease was diagnosed as neuroaxonal dystrophy (NAD) by sural nerve biopsy at the age of 7. Further course was characterized by complete loss of all motoric and sensory functions and dementia as well. Finally there was decerebration. The autopsy revealed generalized NAD associated with pallidal deposition of iron pigment to classify as generalized intermediate NAD type II according to Gilman and Barrett (1973). The main histological findings were axonal swellings and spheroids consisting ultrastructurally of membrano-tubular profiles, lamellar structures, vacuoles, glycogen granules and mitochondrial aggregates. Immunohistologically there was partial positive expression of synaptophysin and neurofilament protein in the spheroids. Firstly described electron microscopical findings in the retina include the typical axonal lesions largely in interior layers. Photoreceptors and their synaptic contacts were preserved. The present blindness is of the neuronal type. The current etiopathogenetic opinions, aspects of bioptic diagnosis and problems of classification of primary NADs are discussed. PMID- 1584982 TI - [Qualitative studies of Fahr disease]. AB - We investigated brain tissue from 7 deceased patients with Fahr's disease using X ray-analysis for the determination of compositional differences between calcareous particles in different areas of brain or between the left and right sides in a brain and differences in composition of concrements in different brains. We found, in all areas of one brain no difference in elementary composition. Differences were found between different brains, two brains showed a high silicon content. PMID- 1584983 TI - [The histochemical formation of the myoadenylate deaminase reaction in human skeletal musculature]. AB - Muscle biopsies from control subjects, patients with neuromuscular diseases and premature infants and neonates were investigated for myoadenylate deaminase activity (MAD) by histochemistry. A histochemically picture of MAD-deficiency is more frequently then the clinically defined MAD-deficiency syndrome with an autosomal recessive pattern of inheritance. The high incidence of the carrier state, secondary MAD-deficiency and connections with other diseases are the causes. An individual predisposition for loading crisis of these patients in a high physical stress situation is probable. PMID- 1584984 TI - [Synaptophysin in the nervous system and endocrine cells]. AB - Synaptophysin is a major integral membrane glycoprotein of neuronal synaptic vesicles that is present in virtually all synapses and shows a high degree of evolutionary conservation in mammalian species. It has also been detected in numerous endocrine cell types where it is localized in the membrane of small synaptic-like vesicles which are thought to constitute a previously unknown secretory pathway. Antibodies directed against synaptophysin are a valuable tool for the immunohistochemical quantitation of synapses. Moreover, synaptophysin is a most reliable and specific marker molecule for normal and neoplastic neuroendocrine cells. In the nervous system, synaptophysin-positive tumors comprise ganglioneuromas, ganglioneuroblastomas, neuroblastomas, paragangliomas and primitive neuroectodermal tumors. PMID- 1584986 TI - Immunohistochemical reactivity of neuropeptides in plastic-embedded semithin sections of the myenteric plexus in infantile hypertrophic pylorus stenosis. AB - Pyloric biopsies obtained at pyloromyotomy from 46 infants were studied by light and electron microscopy and compared to 8 autopsy control cases without any evidence of infantile hypertrophic pyloric stenosis (IHPS). A positive family history of this disorder was recorded in 8 cases (2 girls and 6 boys). The most frequent changes in the myenteric plexus comprised axonal alterations. In glial cells, cytoplasmic vacuolisation or an increase of intermediate filaments occurred. In ganglion cells, vacuolisation of perikaryal cytoplasm or dense bodies were observed. No obvious differences were seen between sporadic and hereditary cases. In addition to these fine structural alterations, immunohistochemistry in 6 IHPS cases and 4 controls revealed differences in the distribution of substance P, bombesin, calcitonin gene related peptide and enkephalin-like immunoreactivity within the myenteric plexus between IHPS and control cases. The immunoreactivity, however, was unevenly distributed from case to case and even within individual cases. The reduction of immunoreactivity corresponded, at least in part, to an increase of neurofilaments or abnormal organelles within axons. Increased immunoreactivity was apparently related to focal accumulation of dense cored vesicles noted in the preceding study. It is suggested that these and other changes reported interfere with the normal gastrointestinal reflex mechanisms leading to intestinal obstruction. PMID- 1584985 TI - Acceleration of nerve and muscle regeneration by administration of nucleotides- electroneurophysiological and morphometrical investigations. AB - The effect of nucleotide administration on the regeneration of myelinated nerve fibres following crush injury to the sciatic nerve of the rat was studied using morphometric techniques. In addition morphometrical investigations of peroneal and soleal muscles were performed at different times. After a localized crush lesion of the right sciatic nerve, rats were given nucleotides daily at a dosage of 3.0 mg/kg body wt uridine monophosphate (UM), 2.5 mg/kg body wt cytidine monophosphate (CMP) or 3.0 plus 2.5 mg/kg body wt UMP plus CMP, respectively. Observations were made after 20, 40 and 60 days of common peroneal nerve regeneration for comparison with age-matched crushed or nonoperated controls. Forty days after daily UMP/CMP administration the single fibre conduction velocity of all type II afferents was significantly accelerated. There was a trend towards increased mean fibre area related to increased myelin area. Mean diameter of type II muscle fibres was increased. After 60 days, there was a trend to increase of single afferent fibre conduction velocity in the UMP/CMP group. In the same group automated morphometry revealed a significant increase of nerve fibre area, myelin area and axon area. At this time an increase was found of type I and/or type II muscle fibres in all animal groups. The present results suggest that both axons (neurons) and myelin sheaths (Schwann cells) of regenerating nerve fibres and regenerating muscle fibres are influenced by nucleotide administration. PMID- 1584987 TI - Neurohistochemical and electron microscopic investigations of pathological and age-related changes in the cardiovascular system. AB - Neurohistochemical and electron microscopic investigations of the autonomic nervous system (ANS) of man and animals suggest that its ontogenesis can be divided into the premediatory, mediatory and postmediatory periods of development. The postmediatory period begins heterochronically in various ganglia of the ANS. A normal process of early cardiac desympathization usually occurs at the age of 35 to 60 years. Specific changes of preceding sudden cardiac death are elicited in different parts of the ANS and adrenal glands. This is accompanied by focal myocardial desympathization. Coronary vessels and conducting system which may influence myocardial hypersensitivity zones to catecholamines are involved in the process of destabilization of the cardiac function. Moreover, relationships are demonstrated which exist between the atherosclerotic lesions of the aortic wall and the status of its nerve plexuses. PMID- 1584988 TI - [Current aspects in diagnosis of Parkinson disease]. AB - The causes of symptomatic parkinsonism are enumerated and discussed including drug-induced, vascular, toxic, postencephalitic and posttraumatic parkinsonism. The environmental hypothesis and the concept of oxidative stress in the pathogenesis of Parkinson's disease are illustrated. The clinical diagnosis, the differential diagnosis and the possible diagnostic errors originating from the cardinal symptoms akinesia, rigor und tremor in the early stages of the disease are delineated. At last the contributions of EEG, CCT, evoked potentials, MRI, PET und the apomorphine test to the diagnosis especially early diagnosis are evaluated. PMID- 1584989 TI - Histochemical and morphometric investigation of the pathogenesis of acute brain infarction in primates. AB - The right medial cerebral artery of 25 primates (Macaca radiata) was occluded transorbitally with an atraumatic clip. The time courses of infarct volume and capillary morphometric changes in the ischemic lenticular nucleus, caudate nucleus and insular cortex were then determined. Volume changes of ischemic foci were studied morphometrically using an enzyme histotopochemical acid phosphatase stain. During the first 4 hours extension (or spread) of the ischemic area was small and constant. Over the next hours, the ischemic focus increased in volume, becoming maximal in the lenticular nucleus in 24 hours and in the caudate nucleus in 48 hours. In the lenticular nucleus, edema developed 4 hours after onset of ischemia and was characterized by a decrease in capillary diameter and an increase in mean intercapillary distance. In the caudate nucleus and insular cortex, in the first hours after clipping the medial cerebral artery, capillary diameter and volume increased and intercapillary distance decreased. The data demonstrate that the therapeutic window of brain infarct treatment is during the first 4-6 hours after occlusion of the medial cerebral artery. PMID- 1584990 TI - [Vascular etiopathogenesis and degenerative dementias--current state of knowledge]. AB - Dementia due to vascular and degenerative abnormalities has become more frequent with increasing life expectancy. Although the origin of both dementia types is still unknown, pathobiochemical perturbations comprising energy loss, lactic acidosis, calcium homeostasis and free radical formation have been found in both dementia types in incipient stages at the neuronal level. A therapeutic rational against these abnormalities is discussed. PMID- 1584991 TI - [The effect of arteriosclerosis on the wall elasticity of the human common carotid artery]. AB - The arterial distensibility and the modulus of volume elasticity of more than 100 isolated human carotid arteries was measured and correlated with arteriosclerosis and aging. The loss of arterial distensibility progresses steadily with aging. Arteries with severe arteriosclerosis and arteries with minimal arteriosclerosis show almost similar distensibility. On the other side the differences between distensibility of arteries with moderate arteriosclerosis and arteries with minimal as well as severe arteriosclerosis, especially in the younger and middle ages, are significant. PMID- 1584993 TI - [The distribution of intermediate filaments in intracranial vessels in humans]. AB - The distribution of intermediate filaments GFAP, Vimentin and Desmin was investigated in normal intracerebral and meningeal vessels in human material. Vimentin is detectable in endothelial cells of all cranial vessels. Moreover Vimentin is expressed in all vascular smooth muscle cells of the brain with the exception of arterioles in the white matter and in the pons. Desmin is only detectable in the tunica media of larger intracerebral arterioles or arteries, larger meningeal veins contain single Desmin positive smooth muscle cells. Immuno electronmicroscopically Vimentin could be shown in endothelial and smooth muscle cells of larger venous and arteriolar vessels. We conclude from our immunohistologic investigation that there is an uneven distribution of Vimentin and Desmin in brain vessels which might reflect some ultrastructural peculiarities of brain arteries. PMID- 1584992 TI - [Malignant angioendotheliomatosis as a rare cause of cerebrovascular insufficiency]. AB - Malignant angioendotheliomatosis, so called intravascular malignant lymphomatosis or angiotropic lymphoma, was found in cerebral hemispheres, spinal cord and nerve roots of a 50-year-old woman who died 4 months after onset of neurological symptoms. The pathological findings were characterised by neoplastic cells within the lumina and wall of small vessels as well as by multiple infarcts in the CNS. Vascular occlusions were caused by tumor cells and secondary changes of the wall. Positive reactions of Common Leucocyte Antigen and B-cell-markers support the idea of a lymphoid origin for the tumor cells. The differentiation to the angiocentric lymphoma as a T-cell tumor and the obscure pathogenesis of this neoplastic process must be clarified in the future. PMID- 1584995 TI - The effects of mechanical stretching on fetal rat lung cell prostacyclin production. AB - A model system was used to determine the effect of stretch on prostacyclin (PGI) production by organotypic fetal rat lung cultures grown on gelatin foam in vitro, measured by RIA of 6-keto-PGF1 alpha (6KF) in the culture medium. The stretching apparatus was programmable for stretch of varying frequency and duration. The effective stimuli for PGI production were: continuous pulsatile stretch greater than intermittent pulsatile stretch greater than permanent stretch (p less than 0.05). The rate of PGI production was greatest in the first 15 min of pulsatile stretch and was associated with a 70% increase in cAMP production (p less than 0.05). When the effect of magnitude of stretch was compared (15% vs 28% extension), there was a significant increase with a maximum in the 28% stretch group double that of the 15% stretch group (p less than 0.01). PGI production in response to pulsatile stretching was inhibited by indomethacin but not by pretreatment with cortisol. These results suggest that the production of PGI by lung cells may be significantly affected by the frequency and magnitude of pulsatile stretching. PMID- 1584994 TI - Endothelin-1 induces stimulation of prostaglandin synthesis in cells obtained from canine airways by bronchoalveolar lavage. AB - Endothelin-1 (ET-1), a potent mediator released by airway epithelial cells, often exerts its effects in the lung through stimulation of arachidonic acid (AA) metabolism. To investigate its range of influence, we studied the action of ET-1 on the synthesis and release of thromboxane (TX)B2, prostaglandin (PG)D2, and histamine from canine airway cells obtained by bronchoalveolar lavage (BAL). ET-1 (10(-10), 10(-9) and 10(-8)M) stimulated production of TXB2 and PGD2 by BAL cell preparations in a dose-related manner in the absence of measurable histamine release. Release of TXB2 was 10-fold higher than that of PGD2. The effect of ET-1 on AA metabolism in alveolar macrophages was evaluated in preparations of purified (greater than 99%) cells labelled for 20-22 hrs with 3H-AA prior to stimulation. ET-1 (10(-8), 10(-7), 10(-6)M) induced significant, dose-related release of 3H-AA and its metabolites from alveolar macrophages, to levels 350% above control. These studies indicate that low levels of ET-1 can stimulate AA metabolism in resident luminal airway cells, including alveolar macrophages, and suggest that the function of these luminal cells may be modulated by the epithelium, in vivo, through the release of this peptide into the airways. PMID- 1584996 TI - Production of 12-hydroxyeicosatetraenoic acid in early pregnant uterine cervix- lack of correlation to mifepristone-induced cervical ripening. A double-blind randomized biomechanical and biochemical study. AB - The regulation of cervical ripening in pregnancy may involve arachidonic acid metabolites. We studied the formation of lipoxygenase products in cervical biopsies from twenty nulliparous women requesting a first trimester abortion. The patients were randomly allocated to receive either 100 mg of the progesterone antagonist mifepristone (RU 486) or placebo 48 and 36 hours before surgery. A capacity to produce significant amounts of 12-HETE and material co chromatographing with leukotrienes was observed in the cervical tissue. No qualitative or quantitative relationship to mifepristone-induced cervical ripening was found. Although our data suggest a large variation of 12-HETE production it remains to clarify its role in the cervix. PMID- 1584997 TI - A potent inhibitor of platelet activating factor from the saliva of the leech Hirudo medicinalis. AB - Leech saliva is shown to contain protein platelet aggregation inhibitors and a range of selective low molecular weight (LMW) aggregation inhibitors. Gel filtration on Bio-Gel P-2 (cut-off kDa) yields a protein fraction (Fr. I) and three LMW fractions. Fr. I inhibits aggregation induced by collagen, ADP, epinephrine and arachidonic acid. Of all the fractions, only one, Fr. II (LMW) specifically inhibits aggregation induced by platelet activating factor (PAF, 1-O alkyl-2-acetyl-sn-glycero-3-phosphorylcholine). Fr. II also inhibits thrombin induced platelet aggregation. Fr. III inhibits aggregation induced by ADP, epinephrine and arachidonic acid, and Fr. IV only that induced by arachidonic acid. Fr. II also inhibits PAF- and thrombin-induced thromboxane generation in platelets, but does not inhibit arachidonic acid-induced thromboxane generation. Efforts to separate the anti-PAF from the anti-thrombin activity have been unsuccessful. The inhibition may therefore be due to a single inhibitor, though it may also be due to several inhibitors. Fr. II also inhibits superoxide anion production in formyl Met-Leu-Phe (fMLP)- and ionophore 23187- stimulated neutrophils. This may be due to the inhibition of the effects of PAF generated within the cell. Preliminary results suggest that the Fr. II inhibitor(s) is (are) amphipathic. The interaction of platelets with PAF and their interaction with the inhibitor(s) are mutually exclusive, and the inhibition may be competitive. PMID- 1584998 TI - Pancreas prostanoid production in ischemia and reperfusion. AB - This study was carried out to investigate the proportion of the 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and thromboxane B2 (TXB2) alteration that is due to ischemia in pancreas transplantation against the proportion due to reperfusion. For this purpose, Lewis rats were divided in three experimental groups: Group I = Control, Group II = Donor pancreas subjected to 15 minutes of cold ischemia, Group III = Same as group II but pancreas were transplanted to the recipient individual and then subjected to reperfusion. The results indicate that increases in pancreas 6-keto PGF1 alpha occur as a consequence of cold ischemia while TXB2 remains unchanged. When blood flow was restored, 6-keto PGF1 alpha remained unchanged compared to the ischemic group while pancreatic levels of TXB2 were significantly increased. These results suggest a different induction of prostanoid metabolism during ischemia and reperfusion in pancreatic tissue. PMID- 1584999 TI - Digital subtraction angiography for leg venography. AB - Venography was performed in 25 legs of 17 patients using digital subtraction angiography (DSA). Reliable diagnoses of deep vein thrombosis or patency were made in the majority of these cases. There were no complications. Multiple injections of contrast material were required to image the entire leg; however, the total quantity of iodine necessary for each leg averaged 9 g, significantly less than with conventional techniques. The preferred method consisted of injecting 15 ml of 100 mg iodine/ml contrast material followed by 15 ml of heparinized saline. DSA proved a safe and useful means of evaluating veins of the leg. PMID- 1585000 TI - Cancer of the oropharynx developed after radiotherapy and chemotherapy for Hodgkin's disease--a case report. AB - A case of oropharyngeal squamous cell cancer occurring in the radiation field for Hodgkin's disease is reported. The second cancer was diagnosed six years and one month after the patient received 40 Gy/25 fractions. The patient also received salvage chemotherapy two years and six months after the primary radiotherapy. In a review of the world literature, we found 22 cases of head and neck cancer excluding the thyroid gland occurring after radiotherapy alone or radiotherapy combined with chemotherapy for Hodgkin's disease. Although second cancers in the head and neck area after Hodgkin's disease have rarely been reported, those patients cured of the disease should be followed up carefully for a long period of time. PMID- 1585001 TI - Determination of vertebral bone mineral density with new dual energy X-ray absorptiometry using multiple detectors: fundamental studies. AB - Fundamental studies on the ability of a newly developed 90-detector dual energy X ray absorptiometry (DEXA) system with a fan beam, the DCS-3000, to determine bone mineral density (BMD) were performed. This new system not only measured BMD precisely, resulting in a fast scan mode in CV of 0.89% and 1.63% for in vitro and in vivo studies, respectively, but also performed data acquisition in a greatly reduced examination time (24 sec). Furthermore, when a rod phantom was used, the linear regression equation obtained between BMD quantified with the QDR 1000 (x) and that quantified with the DCS-3000 (y) was y = 1.250x-0.242. In both healthy subjects and osteoporotic patients, significant positive correlations were obtained between radial BMD and vertebral BMD measured with the QDR-1000 and with the DCS-3000. The correlation for radial BMD was r = 0.533 (p less than 0.001, N = 76), and that for vertebral BMD was r = 0.985 (p less than 0.001, N = 56). Therefore, in addition to safety of operation, the performance of the DCS 3000 was considered to be equal to that of commercially available DEXA systems, indicating that it should be useful in the detection of vertebral bone loss. PMID- 1585002 TI - Percutaneous transfemoral arterial infusion chemotherapy for metastatic liver tumors--placement of 3 Fr balloon catheters. AB - A 3 Fr single lumen balloon catheter was successfully introduced for arterial infusion chemotherapy by percutaneous transfemoral arterial insertion. This balloon catheter was combined with a 6.3 Fr outer catheter coaxially. After placing the catheter into the target artery, the balloon was ruptured by injecting 1 ml of contrast medium. Alternatively, the balloon was made into a leaky balloon catheter by a small needle puncture before use. In 34 patients with liver tumors, we used this method combined with the continuous infusion of 5 fluorouracil for three to five weeks and once-a-week intra-arterial administration of mitomycin C and adriamycin. The result of this therapy was as follows: CR, 8.8%; PR, 29.4%; NC, 50.0%; and PD, 11.8%. No serious complications were encountered in our series except for some minor arterial problems caused by the catheter tip. PMID- 1585003 TI - Seasonal prolactin secretion and its role in seasonal reproduction: a review. AB - The majority of seasonally breeding mammals show a seasonal pattern of prolactin secretion with peak concentrations in spring or summer and a nadir in autumn or winter. Photoperiod influences prolactin secretion via its effects on the secretion of the pineal hormone melatonin. Preliminary evidence suggests that the effects of melatonin on both prolactin and gonadotrophin secretion are via a common target area, possibly within the anterior hypothalamus, and that differences in response to photoperiod may be due to differences in the processing and/or interpretation of the melatonin signal. In contrast to seasonal gonadotrophin secretion, the seasonal changes in prolactin are not due to changes in the sensitivity of a feedback loop and so must be due to direct effects on the hypothalamic pathways that control prolactin secretion. Little else can be said with confidence about the neuroendocrine mechanisms that lead to the seasonal changes in prolactin secretion. Dopamine and noradrenaline turnover in the arcuate nucleus and median eminence decrease under short daylength. If catecholamine turnover in these structures is positively correlated with catecholamine concentrations in the long or short hypophysial portal vessels, it is unlikely that the decrease in prolactin concentration in winter is due to the effects of increased concentrations of dopamine or noradrenaline in the portal vessels. There is, however, evidence for increased pituitary sensitivity to dopamine under short daylength, so increased dopamine concentrations may not be required for suppression of prolactin secretion at this time. In addition to the diminished secretion of prolactin under short daylength, rate of prolactin synthesis and pituitary content of prolactin also decline although the mechanisms that regulate these changes are poorly understood. Although all seasonal breeders show a seasonal change in prolactin secretion, there are continuously breeding species in which prolactin secretion is also under photoperiodic control. It is likely therefore that a seasonal pattern of prolactin secretion is only evidence of neuroendocrine sensitivity to changing photoperiod. Depending upon the species, this sensitivity to the seasonal changes in daylength may or may not be accompanied by seasonal changes in a biological endpoint such as seasonal reproduction or indeed other adaptations. Whether the seasonal change in prolactin secretion is an endocrine mediator of such adaptations remains in contention. Certainly in some species this signal does have a role in reproduction. For example, in species with an obligate seasonal embryonic diapause, the seasonal increase in prolactin can act as a luteotrophin (mink and western spotted skunk) or luteostatin (Bennett's and tammar wallabies.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1585004 TI - Mouse embryos and quality control in human IVF. PMID- 1585005 TI - Outcome of pregnancies resulting from a trial of supplementing human IVF culture media with platelet activating factor. PMID- 1585006 TI - Proline and glycine betaine in cryoprotective diluents for ram spermatozoa. PMID- 1585007 TI - Stimulation of protein synthesis and expansion of pig blastocysts by insulin in vitro. AB - Present evidence indicates that insulin may act as a growth factor during preimplantation development. This hypothesis has been tested on pig blastocysts by determining the effect of insulin on protein synthesis and blastocyst expansion over 24 h. Blastocysts were collected from superovulated gilts or sows on Day 5 or 6 and incubated overnight in a modified BMOC2 medium. Those that were cultured with 1.7 nM insulin had 14% larger radii, and were 36% more active in their incorporation of [3H]leucine (protein synthesis) than those that had been cultured in non-supplemented medium. There was a significant linear correlation between the rate of protein synthesis and the radius of blastocysts when all blastocysts and only those cultured with insulin were examined, but the correlation for the blastocysts in non-supplemented medium was just outside statistical significance. The regression coefficient for the insulin-treated blastocysts was 132% of that for blastocysts cultured in unsupplemented medium; this suggests that insulin increased the size of blastocysts and the rate of protein synthesis per unit size. The results indicate that pig blastocysts respond to physiological levels of insulin in similar fashion to those of mice and cattle, supporting the hypothesis that insulin may act as a general embryonic growth factor. Because of the cross reaction between the insulin receptor and the ligands, insulin and insulin-like growth factor 1 (IGF-1), the results also suggest that IGF-1, reported to be present in pig uterine fluid, could be involved in this stimulation in utero. PMID- 1585008 TI - Effects of the ovary, sucking stimulus and season on the pattern of LH and FSH release in the female tammar, Macropus eugenii. AB - The sequential effects of removal of the corpus luteum, removal of the non-luteal ovary and sucking stimulus and the effects of season of the year on the release of luteinizing hormone (LH) and follicle stimulating hormone (FSH) have been determined in the tammar wallaby, Macropus eugenii. Plasma concentrations of LH and FSH were measured at 15 min intervals for 6 h in eight animals at four successive times in the breeding season (lactational quiescence); (A) while they were intact and lactating, (B) 10 days after removal of the ovary bearing the quiescent corpus luteum, (C) 21 days after bilateral ovariectomy and (D) 21 days after removal of the sucking stimulus, and (E) in the following non-breeding season (seasonal quiescence). Single blood samples were taken twice weekly during lactational quiescence. In the presence of ovarian tissue, basal concentrations of LH were low (0.94 ng mL-1) with pulses of low magnitude (1.3 ng mL-1) and low frequency (1.4 pulses per 6 h). There was no response to luteectomy but all three parameters increased after bilateral ovariectomy. Removal of the sucking stimulus affected the LH pulse frequency but seasonal differences were not evident. The pattern of release of FSH was not pulsatile. There was no response to luteectomy in basal concentrations of FSH but these rose significantly after bilateral ovariectomy (P less than 0.001) in lactational quiescence. There was no effect of removing the sucking stimulus but in seasonal quiescence concentrations were higher. The results indicate that non-luteal ovarian tissue is essential for the negative-feedback effects on LH and FSH secretion, that the pattern of release of LH, but not FSH, is pulsatile, and that there is no marked seasonal change in hypothalamo-hypophysial activity. PMID- 1585009 TI - Maternal recognition of pregnancy in the Tasmanian bettong, Bettongia gaimardi (Marsupialia: Macropodoidea). AB - The fetus of the marsupial Bettongia gaimardi, the Tasmanian bettong, has both morphological and cytological effects upon the gravid uterus. Development of diapausing embryos or the initiation of oestrous cycles was achieved by removal of the pouch young (RPY). Increases in the diameter of the uterine basal endometrial glands were noted 3 and 4 days later. An animal at Day 5 after RPY had glands in the gravid uterus that were significantly larger than those in the non-gravid uterus (P less than 0.01). This difference was also found in non pregnant animals before Day 11 and was believed to be due to the local presence of the corpus luteum. Thereafter, significant differences were only found in pregnant animals until parturition at Day 17 or 18 after RPY. These differences were attributed to the local effect of the fetus and reflect a 'maternal recognition of pregnancy', as found in other macropodoid species. PMID- 1585010 TI - Effects of photoperiod on the reproductive physiology of male flying foxes, Pteropus poliocephalus. AB - Melatonion concentrations were determined in plasma pools obtained from adult male Pteropus poliocephalus (autumn mating season) at four times of the year. Melatonin levels increased within 3 h of sunset and remained elevated for the duration of the scotophase at all times of the year. Two photoperiod manipulation experiments were performed to examine the role of daylength in the regulation of the timing of the breeding season of this species. In Experiment 1, three adult males were transferred from natural short days to 16L:8D for 137 days and then photoperiod was progressively decreased over 120 days to 9L:15D; this photoperiod was then maintained for 350 days. Testicular volume (TV) peaked during decreasing photoperiod well before the time of maximal size in natural conditions. During the period in extended short photoperiod these bats showed several cycles of TV change with a progressively decreasing interval between cycles. In Experiment 2, nine adult males were exposed to the same shift to 16L:8D as in Experiment 1, but were subsequently split into three groups: 8L:16D, progressive decrease to 8L:16D and maintenance in 16L:8D. The 8L:16D and decreasing photoperiod groups showed coincident premature increases in TV, as in Experiment 1, whereas in the 16L:8D group TV increased at about the same time as in animals in natural photoperiod. Melatonin determination in the different experimental groups showed that duration of secretion was related to the length of the scotophase in all cases. These experiments demonstrate that regulation of the timing of reproduction in males of this species is influenced by changes in daylength. PMID- 1585011 TI - Acute effect of PMSG on ovarian androgen-binding sites in the intact immature female rat. AB - Androgen-binding activity in ovaries containing only immature follicles is compared with that in ovaries stimulated with pregnant mare serum gonadotrophin to induce development of large preovulatory follicles. The androgen-binding sites present in cytosols prepared from unstimulated ovaries exhibited kinetics, affinity and a range of specificities for natural and synthetic androgens consistent with those exhibited by the androgen receptor isolated from androgen sensitive tissues. Studies of sedimentation and DNA binding suggest that the receptor-like androgen-binding site present in unstimulated ovaries exists as the 'non-activated' form which is able to undergo transformation and bind to nuclear DNA. Properties of the androgen-binding sites isolated from ovaries stimulated with gonadotrophin were very different from those of the androgen receptor present in unstimulated ovaries. Specificity for androgens was reduced, capacity for dihydrotestosterone (DHT) and methyltrienolone (R1881) increased and androgen binding activity was associated exclusively with the 4.5S form which was not able to bind to nuclear DNA. These data confirm that a shift from a receptor-like to a nonfunctional androgen-binding site is associated with the development of ovulatory follicles and suggest that shifts in androgen-binding populations will determine the response of developing ovarian follicles to androgens. PMID- 1585013 TI - Corpus luteum and endometrial function in ewes post partum: a study in vivo and in vitro. AB - Induction of ovulation post partum is associated with a high incidence of prematurely regressing corpora lutea. However, inadequate luteal function is not the sole reason for pregnancy failure, because ewes with normal corpus luteum function and successful fertilization also fail to establish pregnancies. The effects of suckling status and the interval from post partum to rebreeding on corpus luteum and endometrial function were examined in vivo and in vitro. Ewes were weaned early or allowed to lactate, induced to ovulate using a progesterone impregnated controlled internal drug release device and an intramuscular injection of pregnant mare serum gonadotrophin, and inseminated (intrauterine) at either 21 or 35 days post partum (n = 10 per group). A further 10 standard ewes whose interval from parturition was in excess of 150 days were included for comparative purposes. On Day 10 after insemination the pregnancy rate was determined in four ewes from each of the post-partum groups and five standard ewes. These ewes were then ovariectomized and hysterectomized for studies in vitro. The incidence of premature luteal regression, as assessed by progesterone concentrations in peripheral blood was independent of the suckling stimulus but dependent on stage post partum (21 days post partum, 6 of 19 ewes; 35 days post partum, 0 of 19 ewes; P less than 0.05). Luteal function was normal in all standard ewes. Ovulation rate, corpus luteum weight, corpus luteum progesterone content and basal progesterone production in vitro were significantly less in 21 day than in 35-day post-partum ewes. Pregnancy rates as determined on Day 10 or at term were low in all post-partum groups (7 out of the 38 ewes inseminated) compared with standard ewes (8 of 10). Uterine function was assessed by culturing endometrial tissue from the tip and body of each uterine horn in the presence of [3H]leucine for 30 h at 37 degrees C. Incorporation of radiolabel into non dialysable proteins synthesized and secreted by the endometrium in vitro was independent of uterine horn location and suckling status but was significantly lower (P less than 0.001) in media from 21-day than from 35-day post-partum ewes. Irrespective of treatment group, incorporation of radiolabel was positively correlated with mean plasma progesterone concentrations on Days 2-10 after insemination and with basal progesterone production in vitro. Secreted proteins were detected by two-dimensional-polyacrylamide-gel electrophoresis and fluorography.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1585012 TI - Control of inhibin production by dispersed human luteal cells in vitro. AB - The production of inhibin in vitro by dispersed cells from early to mid (Days 16 19) and late stage (Day 23) human corpus luteum (CL) was examined, and the effects of human chorionic gonadotrophin (hCG), follicle stimulating hormone (FSH), oestradiol and testosterone on inhibin production were determined. Corpora lutea from five subjects in the early to mid luteal stage and three subjects in late luteal stage were dispersed with enzymes and the luteal cells cultured in medium supplemented with 5% calf serum and either FSH (1, 10 or 100 ng mL-1), oestradiol-17 beta (2.5, 5 or 10 micrograms mL-1) or testosterone (0.25, 1 or 5 micrograms mL-1) with or without hCG (1 I.U. mL-1). Cells were cultured for 1 to 3 days without changes of medium, and the concentrations of progesterone, oestradiol and immunoreactive inhibin in the medium were measured by radioimmunoassay. Cells from both types of CL produced inhibin in vitro under basal conditions, but only cells from early to mid CLs responded to hCG with a significant increase in inhibin production. Both progesterone and oestradiol production were stimulated by hCG in both groups of CL. Inhibin concentrations in the cell cultures declined with time in culture, particularly in the late CL group, whereas the concentration of steroids increased. Neither FSH, oestradiol nor testosterone significantly changed inhibin production in either CL group. It was concluded that inhibin production by human luteal cells in vitro is influenced by the age of the CL, and is dependent on LH (hCG) but not on FSH or sex steroids. PMID- 1585014 TI - Time of ovulation in merino ewes superovulated with PMSG and FSH-P. AB - An experiment examined the effects of treatment with gonadotrophin releasing hormone (100 micrograms GnRH injected 24 h after progestagen sponge removal), season of treatment (autumn v. spring), the effect of supplementary feeding with lupin grain (in autumn only, from 12 days before until 8 days after sponge removal) on the time of ovulation in 182 mature Merino ewes superovulated with a combination of 400 I.U. pregnant mare serum gonadotrophin (PMSG) and 12 mg follicle stimulating hormone (FSH-P). Time of ovulation was influenced by both season and the administration of GnRH. Two peaks of ovulation were observed in spring, the first between 24 and 30 h after sponge removal, and the second commencing 42 h after sponge removal. In autumn, there was one peak of ovulation between 42 and 54 h after sponge removal. Treatment with GnRH advanced the time of ovulation in autumn (P less than 0.05), but had no apparent effect in spring. In contrast to the effect of GnRH, time of ovulation for ewes treated in autumn was delayed (P less than 0.001) by supplementary feeding with lupins. PMID- 1585015 TI - Is there a function for ovarian oxytocin in primates? PMID- 1585016 TI - Partial characterization of four forms of immunoreactive gonadotropin-releasing hormone in the brain and terminal nerve of the spiny dogfish (Elasmobranchii; Squalus acanthias). AB - Four forms of immunoreactive GnRH have been detected in tissue extracts of both whole brains and terminal nerves from the spiny dogfish (Squalus acanthias). The GnRH forms were characterized using reverse-phase high pressure liquid chromatography (HPLC) and immunological recognition with four different antisera. Three of these forms possess immunological and chromatographic properties consistent with known forms of GnRH: mammalian GnRH, chicken GnRH-II and salmon GnRH. An additional form, with an HPLC elution position intermediate between chicken GnRH-II and salmon GnRH appears to be a new structure of GnRH. The presence of all four GnRH forms in the terminal nerve suggests a lack of regional specificity of the expressed forms of GnRH in the brain. PMID- 1585017 TI - Locustakinin, a novel myotropic peptide from Locusta migratoria, isolation, primary structure and synthesis. AB - The isolated hindgut of the cockroach, Leucophaea maderae is a very efficient bioassay tool for the monitoring of certain structural types of insect myotropic peptides during HPLC purification. Using this detection system, a six residue peptide has been isolated from an extract of 9000 brain corpora cardiaca-corpora allata suboesophageal ganglion complexes of Locusta migratoria. Amino acid composition and sequence analysis combined with enzymatic digestion data established the structure of the novel peptide as Ala-Phe-Ser-Ser-Trp-Gly-amide. The chromatographic and biological properties of the synthetic peptide were the same as those of the native peptide, thus confirming structural analysis. The carboxy-terminal pentamer sequence is the active core of leucokinins II, V and VII and of achetakinin III (myotropic neuropeptides isolated from Leucophaea m. and from Acheta domesticus; Holman et al., 1990). Furthermore, the octapeptide leucokinin VII contains the novel sequence as its carboxy-terminal hexamer and Achetakinin V (AFHSWGamide) differs from it by one residue. This new peptide designated as locustakinin I (locusts) may therefore represent an evolutionary molecular link between leucokinin VII (cockroaches) and achetakinin V (crickets). Using synthetic locustakinin, physiological studies will be performed in the locust. In view of the known effects of leucokinins, locustakinin may be important in the stimulation of ion transport and inhibition of diuretic activity in Malpighian tubules. This study indicates that the AFXSWGamide sequence appears to have been well conserved and that members of this peptide family may be widely distributed among insects and posses a number of functions. PMID- 1585018 TI - The characterization of radioimmunoassay for rat pancreatic polypeptide in serum. AB - A radioimmunoassay for the measurement of rat pancreatic polypeptide (RPP) in serum or plasma has been developed and characterized using a new guinea-pig anti rat-PP antibody. The assay provides a high degree of sensitivity and lacks cross reactivity (CR less than 0.01%) to neuropeptide Y and peptide YY. It also does not interact with PPs of other species or peptide hormones namely, amylin, glucagon, human insulin, human-PP, human-proinsulin, rat C-peptide and rat insulin. The assay employs synthetic rat PP as standards from concentrations of 21-2100 pg/ml (i.e., 5-500 pM) and produces a sensitivity limit of 19 pg/ml (4.5 pM) PP at +/- 3 S.D. The intra- and interassay % coefficient of variations are 6.4% and 5.9%, respectively. The % recovery of RPP added to rat serum samples ranges from 98% to 103%. Assay of serum volumes ranging from 25 microliters to 100 microliters does not significantly alter the expected RPP level. The migration patterns of rat serum PP and that of a synthetic RPP are identical by Sephadex G-50 chromatographic analysis. The mean values of fasting and a 2 h post feeding plasma RPP levels in normal rats are 40 +/- 2 and 80 +/- 10 pg/ml (9.5 pM and 19.0 pM), respectively. Rat-PP release during insulin induced hypoglycemia in conscious rats rises from 38 +/- 5 pg/ml to 261 +/- 34 pg/ml (9.0 to 62.1 pM, P less than 0.005) by 30 min. Additionally, the antibody used in this study cross reacts well with mouse-PP as determined by linear serum dilution curves, thus making it useful in the measurement of murine-PP. In conclusion, we have developed and validated a sensitive and specific rat-PP assay. This assay provides a new tool for the reliable measurement of PP in physiologic studies using rat and mouse animal models. PMID- 1585019 TI - Cat gastrinoma and the sequence of cat gastrins. AB - Following the curative resection of a pancreatic gastrinoma in a cat, gastrin peptides were purified from the tissue and sequenced. The sequence of cat gastrinoma G17 (18-34) confirms the previously published sequence. The sequence of cat G34 (1-34) is reported for the first time. The NH2-terminal portion of cat G34 differs from that of dog by having a Q (Gln) for L (Leu) at position 10 from the NH2-terminus. PMID- 1585020 TI - The behavioral and social ecology of community houses. AB - A small community home model for severely and profoundly mentally retarded adults is defined in terms of its program orientation, program structure, and program procedures. The model is compared to institutional settings and larger community units by collection of two data sets. The small homes were found to produce beneficial client functioning and high levels of staff/client interaction appropriately related to clients' degree of mental retardation. How staff distributed their attention to clients differed between the three types of settings. A conclusion is offered that the quality of residential care is dependent on the interaction of variables rather than on the presence of any single overridingly powerful factor. PMID- 1585021 TI - Some issues in staff training and improvement. AB - In 1988, Norway's parliament instituted the systematic deinstitutionalization of the nation's health care system for mentally retarded persons. Professionals have recognized that deinstitutionalization will succeed only if treatment personnel can provide effective treatment for their clients. A study is presented in which 152 hands-on staff members were assigned to 76 clients with moderate to severe mental retardation. The study asked whether staff training in behaviorally oriented treatment and assessment would produce greater improvement in the behavior of clients and staff than would training in treatment alone. Data failed to support this hypothesis, but did provide clear evidence that both clients and staff improved with staff training. The assessment of such programs is seen to be of great importance in view of the fact that deinstitutionalization will leave the majority of mentally retarded clients in Norway in the care of persons who have received such limited forms of training. PMID- 1585022 TI - Transfer of staff training from workshops to group homes: a failure to generalize across settings. AB - Two experiments were conducted to assess acquisition and generalization of skills acquired in a workshop by trainees who were primary caregivers on the staffs of group homes for developmentally disabled clients. In Study 1, 31 staff trainees received an intensive, 1-week workshop in behavioral theory and treatment techniques. When assessed at the workshop site, these staff trainees showed increased treatment skills, relative to 18 staff trainees who did not participate in the workshop. In Study 2, pre- and postworkshop observations were taken on 53 developmentally disabled clients in group homes where the staff trainees worked. These observations provided no evidence that the workshop had any effect on group home client functioning. Future training programs for caregivers may be more successful if they occur in the group home, involve clients in the home, and enlist the support of supervisory staff, rather than focusing only on primary caregivers. PMID- 1585023 TI - Behavior analysis of residential program development. AB - When institutions are viewed not as locales but as forms of organizing and regulating human behavior, we see that we "deinstitutionalize" by changing the way we organize and regulate, not necessarily by moving people about. This paper examines residential program development as a process of designing and developing community learning environments. The paper asks "What are the essential behaviors of designing community environments?", that is, what do residential program developers do? Six essential dimensions of program development are identified, and each dimension is critiqued in terms of contemporary practices and needs for innovation. The paper concludes that behavior analysts can play an important role in changing the nature of human service organizations. PMID- 1585024 TI - Deinstitutionalization at a large facility: a focus on treatment. AB - This paper describes deinstitutionalization efforts at a large facility. The implementation of a behavioral model and development of specific training curricula are described. Emphasis was placed on the design of individualized treatment services. The quality assurance mechanisms utilized included internal monitoring systems as well as evaluations conducted by external agencies. Client treatment programs were geared toward the acquisition of skills necessary for successful community integration. Finally, it is emphasized that clients in all facilities are entitled to effective and appropriate treatment based on their individual needs and not based on client building size. PMID- 1585025 TI - Review of Psychology on a Disk from CMS academic software: interactive activities for psychology. AB - Psychology on a Disk contains a variety of simulations that show a strong potential to motivate and educate introductory psychology students with a wide range of ability and initial interest. The exercises appear to be well within the grasp of first-year students and provide suitable starting points for discussion of terms, definitions, and areas of research activity. The quality of the simulations is high and provides some indication that there are additional areas of undergraduate psychology, for example, courses in abnormal, clinical, and developmental topics, in which specialized simulations might also constitute an important adjunct to classroom and laboratory activities. The 10 simulations span much of the content of introductory courses, although they are most pertinent to syllabi that emphasize learning principles and social psychology as important foundations. As an instructional device, the simulations also will serve to introduce some students to use of computers as a source of information and feedback with potential benefits in other and later academic endeavors in which time-savings will be important. Promotional materials describe POAD as easy to add (to existing texts), easy to use, easy to grade, easy to afford, and easy to order (through your college bookstore): truth in advertising. PMID- 1585026 TI - Development of a continuum of services for children and adults with autism and other severe behavior disorders. AB - The development of a 12-step continuum of services for individuals with autism is described. The operation and funding of outreach parent training; homebased early intervention; preschool, vocational, and adult intermediate care; and school consultation programs are outlined. The use and importance of evaluative data on both treatment outcome and staff skills are emphasized. PMID- 1585027 TI - [Obesity and mortality. Italian epidemiologic data]. AB - The relationship of indicators of obesity, such as the body mass index (BMI) and the skinfold thickness in some areas (SKIN) to all causes mortality have been analyzed in three italian epidemiological studies. They are the Seven Countries Study--italian areas conducted on 2480 men at entry and followed-up for 25 years; the Brisighella study conducted on 1123 men and 1100 women aged 30-69 and followed-up for 15 years; and the NFR study in Rome conducted on 3395 men aged 46 66 and followed-up of 6.5 years. The univariate analysis concerning the BMI for various age groups, the two sexes, and variable periods of follow-up has almost systematically showed a parabolic inverted J shaped relationship with minimal levels of risk for BMI values of 27-29 units. However this was not the case for the women group and for the oldest men where no clear relationship was found. The analysis concerning the SKIN provided similar but less clear-cut results. The multivariate analysis has confirmed the parabolic relationship of BMI to all causes mortality even in the presence of other 4-5 covariates. The left branch of risk is higher than the right one and its slope could be reduced, although not completely, by the exclusion of heavy smokers, of those who died within the first 5 years of follow-up, of those who were carriers of severe diseases at entry examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585028 TI - [Plasma lipids and apoproteins. The effect of cigarette smoking]. AB - Cigarette smoking produces lipo-apoprotein modifications, which makes it more atherogenic. In this study we have evaluated lipids and apoproteins in 178 normolipidemic, healthy subjects, in relation to their smoking habits. In smokers we have found lower levels of HDL-cholesterol and apo A-I and higher levels of triglyceride and apo B. Number of cigarette smoked in a day directly correlated with triglycerides and apo B (r = 0.321 and 0.313 respectively) and inversely with HDL-cholesterol (r = -0.274). These alterations seem to be due to an inhibition that smoking could cause on lipolytic processes. Further studies need to establish influences that smoking-related alterations have in the atherosclerotic lesions of smokers. PMID- 1585029 TI - [Usefulness of microbial investigations in community-acquired pneumonia]. AB - Community acquired pneumonia (CAP) is a common and well known disease, however there is no definite agreement on a common diagnostic-therapeutic strategy. To evaluate the usefulness of microbial investigations in the clinical practice we performed a prospective study on 93 consecutive patients with a diagnosis of CAP. Group I consisted of 46 patients that underwent a diagnostic protocol including sputum, blood cultures and detection of specific antibodies against M. pneumoniae, adenovirus, respiratory syncytial virus, and L. pneumophila. Group II consisted of 47 patients, in which only sputum samples were collected and cultured. No significant differences concerning the aetiologic diagnosis, the outcome and the length of hospitalization were observed in the two groups. The aetiological diagnosis was obtained in 17 patients (18.3%). As result of information obtained from microbiol tests, antibiotic therapy was changed only in 6 patients. Among the prognostic factors only a low albumin level was correlated with the length of hospitalization (p less than 0.01). From our data, the detection of microbial aetiology should not be routinely performed in patients with CAP, but should be reserved only to the severe forms. PMID- 1585030 TI - [A clinical case of Arnold-Chiari malformation, type I. Neuroradiologic and neurophysiologic study]. AB - The Authors present a case of type I Arnold-Chiari malformation (ACM), with early appearance of clinical symptoms and worsening course of the illness even after surgical treatment. The interest of the case rest both in the rich symptomatology and multiple exams performed which represent the evolution of the neuroradiological techniques of the last thirty years for the study of ACM. Recently, neurophysiologic exams such as somatosensory evoked potentials (SEP) helped to further evaluate these patients. Despite such diagnostic evolution, there is no definite etiopathogenesis. Furthermore, as for therapeutics, the best approach is still the Gardner surgical technique, which, at the moment, is debated for frequent post-operative complications and the absence of significant clinical improvement, especially in the most severe cases. PMID- 1585031 TI - [Hypersplenism from an aneurysm of the splenic artery. A clinical case]. AB - Presentation of one case. Hypersplenism may be caused by a variety of pathological conditions. Rarely, it may be due to some vascular pathology. The Authors report on a patient with an hypersplenic syndrome, caused by the aneurysm of splenic artery, in whom splenectomy has been curative. PMID- 1585032 TI - [Diabetic bullosis. A case report]. AB - Bullosis diabeticorum is a very rare complication of diabetes; few more than fifty cases have been reported in literature. We report on an 80-year-old man with non-insulin dependent diabetes mellitus who showed bullosis diabeticorum relapsing at the leg. We describe the cutaneous feature and the procedure carried out. We analyze the different etio-pathogenetic hypothesis and differential diagnosis, that is always by exclusion. PMID- 1585034 TI - [Functional evaluation of the left ventricle in chronic pulmonary heart disease]. AB - 20 patients (18 m., 2 f., age 64.8 +/- 6.3 years), with chronic pulmonary heart disease (CPHD) secondary to chronic obstructive pulmonary disease and/or arterial hypertension were studied in comparison with a control group of subjects, age and sex matched, with normal respiratory function tests and without heart disease. CPHD patients did not show any difference of left ventricle (LV) systolic function, assessed by echocardiography, in comparison with the control group. However, among CPHD patients, significant correlations were found between lower arterial pH and cardiac output/m2 and between spirometric tests of bronchial obstruction and echocardiographic parameters of LV function. These results confirm that LV function in CPHD is maintained if other pathologic conditions are absent. On the other hand, correlations between echocardiography and spirometry and blood gas analysis strengthen the functional interdependence concept between left and right heart chambers. PMID- 1585033 TI - [Drugs affecting upper respiratory tract motility: cisapride]. AB - The article is a short review of older and more recent drugs aimed to modify the gastrointestinal motility. Cisapride the newer one is considered with particular attention. PMID- 1585035 TI - [Study of thyroid function in patients chronically treated with amiodarone]. AB - The authors studied thyroid function by dosage of total T3 and T4, corresponding free portions, thyroid binding globulin (TBG), thyroid stimulating hormone (TSH) and reverse T3 (rT3) in 68 clinically euthyroid patients, treated with amiodarone, divided in two groups including 25 subjects treated for less than one month and 43 subjects in therapy for more than one month. The data obtained in the first group have been compared with the second one and with data obtained in a group of 40 healthy subjects. The statistical analysis of results showed a reduction of total T3 and free T3 and an increase of TSH, total T4, free T4 and rT3 in each of two groups of treated patients compared with control group, while there was no difference in comparison between the two treated group. PMID- 1585036 TI - [Multiple endocrine neoplasms]. AB - The multiple disorders endocrine neoplasia syndromes are autosomal inherited disorders characterized by typical associations of tumors of the endocrine glands. Three different syndromes have been recognized, the type 1, the type 2A and the type 2B. The gene of the multiple endocrine neoplasia type 1 has been localized on chromosome 11 region q13, while the MEN 2 gene maps on the pericentromeric region of chromosome 10. The few years since the original mapping of the two disease genes have seen considerable effort by several laboratories to refine the localization of the genes and obtain good flanking markers. This effort has two purposes: 1) better presymptomatic "diagnosis" and genetic counselling based on both very close and flanking markers, and 2) definition of the molecular regions containing the MEN 1 and MEN 2 loci as a necessary first step in positional cloning efforts. In most clinical situations it is possible to identify a haplotype with the mutant allele in the middle. The calculated predictive accuracy of this test is greater than 95% for the two syndromes. Therefore, genetic linkage testing can be used for informed genetic counselling in families affected by multiple endocrine neoplasia type 1 and 2. PMID- 1585037 TI - [Pathogenesis and therapy of glomerulonephritis. Reflections on recent advances]. AB - The aim of this review is to describe how antibodies and cells of the immune system induce inflammatory lesions in the kidney. Renal glomeruli and tubules can be damaged not only by antibodies and immune complexes generated in the immune system but also by T lymphocyte-mediated hypersensitivity reactions originated locally. New mediators of inflammation have been identified, including growth factors and cytokines which are essential symbols of a language of intercellular communication modulating cell proliferation, the adhesion of inflammatory cells to the walls of the vessels, and to the extracellular matrix, and the formation of fibrosclerotic tissue contributing to the healing process. The identification of new methods for induction of tolerance to histocompatibility antigens, the identification of antigens responsible for autoimmune diseases of the kidney, and the synthesis of the peptides forming the receptor of T lymphocytes involved in the pathogenesis of an autoimmune disease of the brain, may help to design new therapeutic strategies for renal diseases, based on the inhibition of T lymphocyte activation. PMID- 1585038 TI - [Current view on non-Hodgkin lymphomas. Origin and evolution in relation to cytogenetic-histologic correlations]. AB - Recent advances in immunology, cytogenetics and molecular genetics has allowed for a better understanding of the origin and evolution of non Hodgkin lymphoma (NHL). Over the last decade a number of recurrent chromosome aberrations has been disclosed and some correlations with well defined histologic subsets of B-cell NHL has been established. Five important cytogenetic-histologic associations has been documented, well defined by combined cytologic, immunologic and genetic investigations: t(14;18) (q32;q21) and NHL of follicle centre cell origin, frequently with follicular histologic pattern; t(8;14) (q24;q32) and Burkitt's lymphoma, Burkitt-like lymphoma or the equivalent small non-cleaved cell category of the "working formulation system"; t(3;22) (q27;q11) and diffuse large cell lymphoma; t(11;14) (q13;q32) and mantle zone lymphoma; trisomy 12 and chronic lymphocytic leukemia and well-differentiated small lymphocytic lymphoma. Molecular genetic studies elucidated some mechanisms operating during the normal lymphocyte differentiation which may be held responsible for the illegitimate recombination between the immunoglobulin genes and some oncogenes normally located on other chromosome regions. It has thus been demonstrated that the early events leading to neoplastic transformation in B-cell neoplasias occur in immature lymphocyte precursors in the bone marrow during the assembly of the immunoglobulin heavy chain gene. According to some recent studies chromosome changes may have prognostic value in B-cell NHL and chronic lymphocytic leukemia and may be employed in clinical practice in the construction of proportional hazard models in several histologic subsets of NHL. PMID- 1585039 TI - The influence of timing and suppository use on efficiency and effectiveness of bowel training after a stroke. AB - This study was designed to determine the efficiency and effectiveness of four bowel training protocols for stroke patients (N = 46) differing in two variables: (a) consistent use of suppositories, and (b) time of day scheduled for the bowel training program. Eighty-five percent of the subjects (n = 39) achieved effective bowel training within 1 month. Patients assigned to morning bowel training groups were significantly more efficient than those in evening groups in establishing effective bowel regimens. No significant differences were found between scheduled versus prn suppository use. Efficiency was highest for those assigned to a bowel training group whose time coincided with their previous pattern and lowest for those assigned to a group whose time conflicted with a previous pattern. PMID- 1585040 TI - The experience of recovery following lacunar stroke. AB - Little is known about the experience of recovery following stroke. A longitudinal, descriptive ethnography formed the basis of the study described in this article, in which 120 interviews were conducted over a period of 6 months with 13 individuals who had experienced lacunar infarcts of the internal capsule of the brain. Participants were interviewed within 72 hours of the infarct and during the acute and rehabilitation phases of recovery. This article discusses the experience of the recovering body and plateaus in this recovery, as well as the phenomena of experimentation with tasks, transformation by familiar surroundings, and sequential focus on involved limbs. PMID- 1585041 TI - Poststroke family function: an evaluation of the family's role in rehabilitation. AB - Stroke affects long-term quality of life and well-being for not only the patients themselves but also their families. However, the focus of most rehabilitation programs has been on managing the acute stage of stroke and evaluating the effectiveness of short-term treatments. Families usually share in treatment, especially in the long term, and they are ultimately responsible for the patient's welfare. This article reviews the literature as it relates to the clinical problems that make rehabilitation a family issue. PMID- 1585043 TI - The rehabilitation clinical nurse specialist of the 1990s: roles assumed by recent graduates. AB - Since there are a limited number of master's programs that prepare rehabilitation clinical nurse specialists, it was assumed that most or all graduates of such a program newly established at Thomas Jefferson University in Philadelphia would assume positions in traditional rehabilitation settings. A needs assessment completed before the beginning of the program indicated that these facilities needed and definitely would hire graduates as rehabilitation clinical nurse specialists. A follow-up study, consisting of questionnaires sent to the first graduates and their employers, indicated that several had taken roles in areas not considered traditional rehabilitation settings. This article discusses rehabilitation as an umbrella concept and how that concept possibly influenced graduates in assuming their first position after graduation. PMID- 1585042 TI - The effects of two teaching techniques on recognition and use of function words by aphasic stroke patients. AB - The study described in this article examined two different methods to reteach reading to stroke patients with Broca's aphasia. The first method was a multisensory technique that used visual, verbal, kinesthetic, and tactile input stimuli, while the alternate method used only a visual-verbal input procedure. A single-subject alternate-treatment design was used to compare the two approaches. It was found that word recognition improved in all patients regardless of the method used. The results of this study suggest that nurses who are aware of this problem may plan a simple approach that can help the affected individual overcome the reading deficit. PMID- 1585044 TI - Traveling with technology. AB - This article reports on a 2-week trip in a motor home through the southeastern United States with an oxygen- and ventilator-dependent young woman with muscular dystrophy. The article describes the planning, implementation, and evaluation of traveling with technology. Discussed are the amount and types of equipment and supplies to take on such a trip, modification of equipment and the motor home, the roles and responsibilities of the nurses, interactions with the client and family, and legal issues. The impact of the trip on the client's behavior--which was to transform her from a passive recipient of care to an actively involved participant--is reported. PMID- 1585045 TI - Implementing nursing case management. AB - While nursing literature abounds with information on nursing case management (NCM), articles discussing actual NCM implementation problems, particularly in the acute rehabilitation setting, are virtually nonexistent. As hospitals seek ways to combat the economic and quality problems stemming from fragmented care, nursing case management provides a viable approach. Yet, it is imperative that those seeking to implement case management realize the importance of careful planning in avoiding common pitfalls. This article discusses NCM and uses a case analysis approach to illustrate problems commonly encountered in implementing the care delivery model. Recommendations for ensuring a smooth transition from primary nursing to nursing case management are presented. PMID- 1585046 TI - Learning readiness in rehabilitation patients. PMID- 1585047 TI - The computerization of nursing. PMID- 1585048 TI - [A guide dog in the life of the blind--experiences, insights, considerations]. AB - A guide dog user himself, the author nevertheless sets out to put forth in as unprejudiced a manner as possible the pros and cons of this mobility aid for blind persons. After a brief outline of the history and present situation of guide dog use in Germany, the author addresses the skills such a service animal must be provided with, dealing both with genetic and biographic issues relative to his or her suitability and training. Also, the team, conceived as a differentiated action entity, is set out in some detail due to its unique structure and dynamics, dealing also with its intricate relationship with the environment. Concluding, the author on the one hand addresses the psychologically important adjustment difficulties a person without previous experience in using this aid may be faced with, and on the other the partnership-based position of the guide dog in private and occupational social interaction. PMID- 1585049 TI - [Disordered retrograde memory: diagnostic procedures in brain damage]. AB - The maintenance of old memories subsequent to brain damage is discussed with the particular aim of pointing out problems and possibilities of measuring them post injury. Relationships between forms of brain damage and retrograde amnesia are outlined, and various recent tests designed to measure old memories are specified and assessed. From this survey it is concluded that tests and test batteries are rather heterogenous so far and at best only crudely comparable between studies, and that a clinically practicable (i.e., short), yet valid and reliable test still has to be created. PMID- 1585050 TI - [Rehabilitation and psychotherapy]. AB - Especially the chronically ill and disabled deserve to benefit from "socially integrated psychotherapy" in view of their specific situation of distress, which has often arisen without warning and unexpectedly. Dealing with bodily impairments, there are the so-called "organismic" methods using the hypnoid state as major component that have proven to be highly efficient. Dealt with are autogenic training, guided affective imagery, respiratory feedback and hypnosis. Hypnoid states can be regarded as a third basic state of consciousness in humans (besides waking and sleep). They play a major role in many forms of psychotherapy. The knowledge and selective use of underlying mechanisms enhance the potentialities of psychotherapy. The psychotherapeutic basic dialogue stays in constant accompanying function. We are opposed to a widespread misconception that psychotherapy is a method for the treatment of psychogenic disorders only. We obtained good results in the treatment of palsied patients of extrapyramidal and pyramidal type with hypnosis or autohypnosis as well as with our own model of group psychotherapy (autogenic training with concomitant analytic discussion, over a period of up to nine months). In this set-up we successfully mix patients with psychogenic and with somatogenic disorders. Although not a primarily psychotherapeutic method, respiratory feedback also makes use of the hypnoid state. Good results have been achieved with patients in rehabilitation and chronic pain sufferers. Occasional experience with guided affective imagery have been encouraging. We can conclude that psychotherapy with organically ill patients is indicated and promising. We need more appropriate training, supervision and concomitant scientific research.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585051 TI - [Subsequent rehabilitation treatment after aortocoronary bypass--how often is reintegration into occupational life successful?]. AB - Investigated was the insurance course of 184 insurants of the Landesversicherungsanstalt Oberfranken und Mittelfranken who, in 1986 and 1987, had participated in in-patient rehabilitation procedures immediately following the post-acute stage, i.e. Anschlussheilbehandlung (AHB), after aortocoronary bypass surgery. Nearly 60% of these insurants were granted a pension within the first two years after AHB, half of them on a permanent basis. The pensioning rate is substantially influenced by beneficiary age: all of the 60 to 64 year-olds and almost every second of the 50 to 54 year-olds were granted a pension. Insurants with formal vocational education more often received premature pension than those without formal training. A cardiac load test showed that cardiac efficiency does not correlate with the return-to-work/pensioning rate. Age seems to play an important additional role in this respect, as older beneficiaries were pensioned more often than younger ones, with the same cardiac fitness found for both groups in cardiac load testing. PMID- 1585052 TI - [Exercise and sports therapy for patients with head and neck tumors]. AB - Important aspects in the aftercare of patients with cancer of head and neck can be realized by physical training in a sports group. The aftermath of operative therapy, e.g. loss of motion, imbalances of muscular activity or respiratory movements, can be reduced. The main importance of physical training in a group is the patient's reintegration in a social environment. Evaluating the quality of life of the individual patient we found that this method of psychosocial aftercare can improve subjective quality of life. Therefore, this conception of rehabilitation should not be missing in the aftercare of patients with malignant cancer. PMID- 1585053 TI - [Characteristics of physical therapy of scoliosis patients in adulthood]. AB - Rehabilitation treatment of adult patients with scoliosis essentially is of a secondary prevention orientation. Along with countering curve progression, the main focus is on improving secondary functional impairments of the cardiopulmonary system as well as on the management of scoliosis-induced pain. In patient physiotherapy rehabilitation provides major impacts in these respects, especially since they have proven their worth in obtaining increases in vital capacity, rib mobility, cardiopulmonary functioning, and in reducing scoliosis induced pain complaints. PMID- 1585054 TI - The decline in American children's fitness levels. PMID- 1585055 TI - In search of relevant and credible physical fitness standards for children. PMID- 1585056 TI - Are American children and youth fit? The need for better data. PMID- 1585057 TI - Should the punishment fit the crime? A measurement dilemma. PMID- 1585058 TI - Defining health and fitness: first step toward establishing children's fitness standards. PMID- 1585059 TI - Youth activity versus youth fitness: let's redirect our efforts. PMID- 1585060 TI - A biomechanical analysis of four sprint start positions. AB - The sprint starts of 12 skilled collegiate sprinter/hurdlers were filmed for four different sprint start conditions. Ground reaction forces were collected for the first step out of the blocks and velocities through a 2-m speed trap immediately following the first support phase were recorded. The subjects employed their preferred right-left leg placement in the blocks, while the anterior-posterior spacing of the front block with respect to the starting line and the amount of forward lean in the set position were varied. Four positions were constructed that accounted for anthropometric differences. The four positions consisted of combinations of two arm orientations (forward lean and perpendicular to ground) and two front block to starting line distances (bunched and elongated). Kinematic data were reduced to provide center of mass position and velocity measures and analyzed for critical periods throughout the starting action. Selected critical events from the first step kinetic records were also analyzed. The results indicated that the elongated starting positions resulted in greater horizontal displacement, greater propelling impulse, increased first step toe-off velocity, and greater average velocity through a 2-m speed trap. Arm orientation effects were less well defined. Forward lean tended to result in greater vertical velocity at block clearance and horizontal velocity at first step toe-off, whereas perpendicular arm positioning resulted in greater 2-m speed trap velocity. PMID- 1585061 TI - A comparison of attitudes and exercise habits of alumni from colleges with varying degrees of physical education activity programs. AB - A survey of alumni attitudes about their college physical education activity (PEA) program and current exercise habits was sent to a representative sample (N = 3169) of alumni who had graduated between 1970 and 1984 from four private colleges. The percent returned was 48, 31, 43, and 41 from Colleges A-D, respectively. Three of the four colleges had required PEA programs. College A had an eight-credit-hour requirement, College B required four credit-hours, College C required two credits, and College D did not have a PEA requirement. Results indicated a significant difference among the four colleges in the alumni's perceived value of their college PEA program in terms of its contribution to their knowledge about fitness, attitude towards fitness, and current exercise habits. Additionally, alumni differed in their perception of the health value of exercise and in their frequency of weekly exercise. When alumni exercise behaviors were quantified by aerobic points and classified according to type of activity, no statistically significant differences were found. The conclusion of the study was that the attitudes and exercise behaviors of alumni are related to the type of college PEA requirement; however, aerobic points earned are not affected. Students graduating from colleges with higher PEA requirements demonstrate more positive exercise attitudes and behaviors. PMID- 1585062 TI - Validation of the 12-minute swim as a field test of peak aerobic power in young women. AB - The purposes of this study were to validate the 12-min swim as a field test of VO2 peak in female recreational swimmers and to compare its validity with that of the 12-min run. The results are contrasted with those previously reported on a comparable group of male recreational swimmers. Thirty-four young women completed 12-min swim, 12-min run, tethered swimming VO2 peak, and treadmill running VO2 peak tests within 3 weeks. Mean (+/- SD) 12-min swim and run distances were 597 +/- 82 and 2,313 +/- 317 m, and mean tethered swim and treadmill run VO2 peak values were 39.2 +/- 4.9 and 45.4 +/- 6.3 ml.kg BW-1.min-1, respectively. Correlation coefficients and standard errors of estimate for predictions of swimming VO2 peak from the 12-min swim (.42 and 4.5 ml.kg BW-1.min-1) and run (.58 and 4.1 ml.kg BW-1.min-1) and for predictions of treadmill run VO2 peak from the 12-min swim (.34 and 6.0 ml.kg BW-1.min-1) and run (.87 and 3.2 ml.kg BW 1.min-1) indicated that the 12-min run was a more accurate predictor of tethered swim or treadmill run VO2 peak than the 12-min swim. These data are in close agreement with our previous study on young male recreational swimmers. We conclude that the 12-min swim has relatively low validity as a field test of peak aerobic power and that it is not an equally valid alternative to the 12-min run in young adult female recreational swimmers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585063 TI - Alternating actual and imagery practice: preliminary theoretical considerations. AB - The main purpose of the following experiments was to reexamine the acquisition effects of alternating actual and imagery practice on retention. This was accomplished by making retention comparisons between groups that either alternated actual and imagery practice, alternated actual practice and rest, employed all actual or all imagery practice, or performed an unrelated task (the control) during acquisition. Results from Experiment 1 indicated that the actual practice and the alternating actual and imagery practice groups produced equivalent scores that were greater than the equivalent scores of the imagery practice and alternating actual practice and rest groups. All experimental groups performed better than the control. Because the retention test was identical to the actual practice protocol, practice specificity may have biased the retention relative standings in favor of the actual practice group. Experiment 2 was identical to Experiment 1 except subjects were transferred to a contralateral limb retention test. Results indicated that the alternating actual and imagery practice group produced better retention scores than the equivalent retention scores of the actual practice and imagery practice groups. These three groups produced higher retention scores than the alternating actual practice and rest group, which was better than the control. These results support the notion that alternating actual and imagery practice facilitates motor learning and suggest that practice specificity may be a factor in response imagery experiments. Based on the notion that actual and imagery practice activate shared and unique mechanisms, several hypotheses were offered to explain these results. PMID- 1585064 TI - The role of teacher knowledge in elementary physical education instruction: an exploratory study. AB - The purpose of this study was to describe how providing teachers with research based knowledge about developmental throwing can influence teachers' observational interpretations and their students' practice patterns. Eight kindergarten classroom teachers with high generic teaching skill competence taught a 6-week overhand throwing unit to the children in their intact classes. Prior to the unit, four of the teachers were randomly assigned to a 4-hour knowledge training program. The other four teachers served as a comparison group (underwent no knowledge training). During the unit, data from stimulated recall interviews were used to describe and compare the thoughts and knowledge concepts expressed by the two groups of teachers. The throwing practice experienced by the children in the knowledge-trained and comparison teachers' classes was videotaped and analyzed for frequency of opposite foot stepping. The knowledge acquired during training was associated with different patterns of skill observation. The knowledge concepts the teachers acquired during training formed the basis of many of their thoughts and were reflected in the instructional procedures implemented. The knowledge-trained teachers' classes demonstrated more than twice as many opposite foot throws during the unit than the comparison teachers' classes. PMID- 1585065 TI - An analysis of the readability of exercise promoting literature with implications and suggestions for practice. PMID- 1585066 TI - A comparison of the sit and reach and the modified sit and reach in the measurement of flexibility in women. PMID- 1585068 TI - Interrater reliability of 1987-1991 Research Quarterly for Exercise and Sport reviews. PMID- 1585067 TI - Effects of postural set on anticipatory muscle activation prior to rapid arm flexion. PMID- 1585069 TI - Commentary on "Research on teaching in physical education". PMID- 1585070 TI - In praise of pedagogy: Silverman, RT-PE, and the illogical separation of teaching and learning. PMID- 1585071 TI - Are American children and youth fit? AB - We analyzed data from the National School Population Fitness Survey (Reiff et al., 1986) and data collected by the authors of the original study to assess the fitness of American children and youth based on the results of additional analyses. We then compared the numbers of children and youth meeting norm referenced standards to numbers meeting recently adopted criterion-referenced health (CRH) standards for individual test items in the FITNESSGRAM (Institute for Aerobics Research, 1987) and AAHPERD Physical Best (AAHPERD, 1988) test batteries. The number of children and youth meeting CRH standards for multiple items in a test battery was also determined. Finally, data were analyzed to determine if changes in fitness have occurred among American children and youth over recent decades. Our results suggest that, with the exception of measures of arm and shoulder girdle strength/endurance, more children and youth meet criterion-referenced health standards than norm-referenced standards (50th percentile) and the majority of American children and youth meet CRH standards for individual test items. However, the majority of American children and youth cannot meet the CRH standards for a battery of items for either of the two batteries studied. A second look at decade to decade comparisons of fitness produced evidence that questions the idea that youth are less fit now than in previous years. PMID- 1585072 TI - Oestrus synchronisation and fertility in black Bengal goats following administration of progesterone/prostaglandin and gonadotrophins. AB - Oestrus synchronisation, fertility and kidding behaviour were studied in 44 Black Bengal goats. They were divided into six experimental groups: group 1, control; group 2, progesterone; group 3, progesterone, pregnant mare serum gonadotrophin (PMSG) and human chorionic gonadotrophin (HCG); group 4, prostaglandin F2 alpha (PGF2 alpha); group 5, PGF2 alpha, PMSG and HCG; group 6, PMSG and HCG. There was 100 per cent synchronisation of oestrus in the groups treated with progesterone, progesterone with PMSG and HCG, and prostaglandin with PMSG and HCG. In the other two treated groups the synchronisation was between 66 and 75 per cent. In the control group only 50 per cent of the animals came into oestrus during the period of observation. The duration of oestrus varied between 19 and 24 hours except in group 5 where it was 40.87 hours. Animals came on heat between 95 and 137 hours after treatment except in group 5 where the interval was only 18.87 hours. A maximum fertility of 75 per cent was observed in group 4 while the kidding percentage was greatest in group 2. There appeared to be no beneficial effect of superovulation on the number of kids produced. Gestation length was similar in all the groups. PMID- 1585073 TI - Increased vascular permeability and leucocyte emigration in Escherichia coli endotoxin injury in the chicken skin. AB - The permeability response was examined in chickens following intradermal injection of Escherichia coli endotoxin. The 'dye' and 'colloidal carbon' techniques were employed. The endotoxin evoked a monophasic response of immediate prolonged type. The increase in vascular permeability was confined to venules and small veins only, indicating its mediation by endogenous permeability factors. The carbon labelling exhibited arboreal, disjointed and rectangular to hexagonal patterns. Histologically, a striking feature of the reaction was an accumulation of basophils in unusually large numbers. No other type of stimulus appears to induce basophilic response of a similar magnitude in the chicken. The results suggest that endotoxin, being a bacterial product, may exert a chemotactic effect on basophils. Hyperaemia, oedema, necrosis and formation of perivascular lymphoid aggregates were also recognised. PMID- 1585074 TI - Onset of insensibility at slaughter in calves: effects of electroplectic seizure and exsanguination on spontaneous electrocortical activity and indices of cerebral metabolism. AB - Cerebral venous and femoral arterial blood samples were collected from 21 young calves either during electrical stunning and recovery or electrical stunning and slaughter by carotid severance or slaughter without stunning. The blood samples were analysed for PO2, PCO2, pH, glucose and lactate. The results were compared with simultaneous recordings of spontaneous electrocortical (ECOG) activity. Calves subjected to head-only electrical stunning and slaughter became permanently insensible at the time of the stun. The six calves slaughtered without stunning lost sensibility within 10 seconds. One calf, in which a clot formed in the carotid arteries inhibiting bleeding, maintained some evidence of cortical activity beyond 52 seconds; this was high amplitude low frequency activity and analysis by Fast Fourier Transform showed sensibility was not regained. In the remaining calves the ECOG activity was lost on average within 49 +/- 3.5 (SEM) seconds after slaughter. The cerebral extraction of metabolites increased after carotid severance, indicating inadequacy of cerebral bloodflow after slaughter. No correlations were found between indices of cerebral metabolism and the time of loss of cortical function. PMID- 1585075 TI - Occurrence of Staphylococcus intermedius on the hair and skin of normal dogs. AB - Aerobic bacterial populations were studied on the distal hair coat and at the skin surface of the shoulder, rump and abdomen of 10 healthy dogs. Coagulase negative staphylococci (CNS) were more frequently isolated from the hair than the skin at the shoulder and rump. There was no difference in the isolation rate of coagulase positive staphylococci (CPS) (Staphylococcus intermedius) between the hair and skin. Total skin counts were greatest on the abdomen whereas CNS counts from the hair were least at this site. There were no differences between CPS counts at the three sites on either hair or skin. The populations on the relatively unfavourable microenvironment of the distal hair may represent contamination rather than colonisation. The low populations of CPS at the skin surface also indicate contamination or transient colonisation rather than true resident status. PMID- 1585076 TI - Effect of glipizide on serum insulin and glucose concentrations in healthy cats. AB - With the recent identification of non-insulin-dependent diabetes mellitus (NIDDM) in cats, new possibilities arise for the use of oral hypoglycaemic agents in the treatment of feline NIDDM, similar to their use in humans. To identify the future applicability of the oral hypoglycaemic agent, glipizide, in the treatment of feline NIDDM, its effects on serum insulin and glucose concentrations in healthy cats was examined. In addition, adverse effects seen clinically or on bloodwork following short-term use of the drug were looked for. Serum insulin and glucose concentrations were evaluated after the oral administration of 2.5, 5.0 and 10.0 mg glipizide and placebo in 10 healthy cats. For each drug trial, blood was obtained five minutes before, immediately before, and 7.5, 15, 30, 45, 60, 90 and 120 minutes after glipizide or placebo administration. Mean serum insulin concentration increased after glipizide administration, with peak mean serum insulin concentration occurring 15 minutes after administration and declining to baseline by 60 minutes. There was no significant difference in peak mean serum insulin concentration, mean serum insulin concentration at 60 minutes after glipizide administration, or mean total insulin secretion between the three glipizide dosages. Mean serum glucose concentration decreased within 15 minutes of glipizide administration, with the glucose nadir occurring 60 minutes after glipizide administration. Placebo trials showed no significant change in mean serum insulin or glucose concentrations from baseline concentrations. PMID- 1585077 TI - Pyrrolizidine alkaloid poisoning of yaks (Bos grunniens) and confirmation by recovery of pyrrolic metabolites from formalin-fixed liver tissue. AB - Severe losses of yaks (Bos grunniens) were investigated in the most eastern region of Bhutan. The most serious disease was a fatal chronic skin disease with emaciation and anaemia. Post mortem examinations revealed major lesions in the liver, consisting of hepatic megalocytosis, bile duct proliferation, fibrosis and remodelling of the hepatic structure. There was also renal megalocytosis, ascites and mild to moderate icterus. Pyrrolizidine alkaloid poisoning was diagnosed and confirmed by demonstrating sulphur-bound pyrrolic metabolites of the alkaloids in preserved liver tissue. Skin lesions with hyaline parakeratosis were an important feature. Similar lesions were found in the mucosa of the oral cavity. No records could be found of such skin lesions in any other species or disease. Pyrrolizidine alkaloid poisoning seriously affects the livelihood of the local population which depends almost entirely on the yak. Various control measures are discussed. The key to be found is the identification of the toxic plants. PMID- 1585079 TI - Resistance to tick-borne fever in young lambs. AB - Lambs were inoculated with Ehrlichia phagocytophila infected blood at the age of either two or six weeks. The temperature response and degree of parasitaemia were both most pronounced in the lambs inoculated at six weeks old. The half-life of antibodies to E phagocytophila was estimated to be 17.5 days. Lambs inoculated with tick-borne fever (TBF) had lower liveweights in the autumn than TBF-free controls. PMID- 1585078 TI - Variation in skin inflammatory responses between sheep bred for resistance or susceptibility to fleece rot and blowfly strike. AB - Sheep which have been bred for resistance (R) or susceptibility (S) to fleece rot and blowfly strike, were tested for intradermal inflammatory responses to excretory and secretory products of Lucilia cuprina larvae. R rams and lambs gave significantly larger skin weals than S animals. In addition, R and S rams were infected with L cuprina first instar larvae and wound exudates were collected. In the first 12 hours of infection R rams released significantly more exudate protein at the wound site than S rams. Correlations suggested that exudate production was stimulated by both larval burden and inflammatory responses, however, in the R group the inflammatory correlation was positive while in the S group it was negative. The results imply that inflammatory responses may play a role in innate resistance to L cuprina. The difference in inflammatory responses suggests genetic differences between the flocks and therefore could show some potential as a trait for indirect selection for resistance to fleece rot and body strike. PMID- 1585080 TI - Effects of dietary molybdenum on nematode and host during Haemonchus contortus infection in lambs. AB - The addition of molybdenum (0.05 mmol kg-1 dry-matter) to the diet of lambs given a trickle infection of Haemonchus contortus larvae (500 third stage larvae d-1 over six weeks) reduced mean faecal egg counts (epg) from 3952 to 2312 +/- 402 by 32 days (P less than 0.02) and greatly reduced the mean number of worms recovered from the abomasum 14 days after infection ceased (907 compared with 4167: P less than 0.01). Infection reduced haemoglobin concentrations less in lambs given molybdenum although the difference was small relative to the reduction in worm burden. Lambs not given molybdenum had low intraepithelial mast cell counts in the abomasal mucosa and less abomasal hypertrophy than expected from abomasal parasitism. Molybdenum did not consistently reduce the copper status of the host or the parasite. Previous exposure to molybdenum greatly reduced protein but not proteinase activity in, or secreted by, adult worms cultured for eight hours. It is suggested that molybdenum either increased the inflammatory response which preceded worm rejection or that it indirectly enhanced that reaction by reducing the effectiveness of copper-dependent, anti-inflammatory enzymes in the gastrointestinal mucosa. PMID- 1585081 TI - Effect of chloramphenicol on sister chromatid exchange in bovine fibroblasts. AB - The genotoxic potential of different chloramphenicol concentrations (5, 20, 40 and 60 micrograms ml-1) was investigated in bovine fibroblast primary lines by sister chromatid exchange assay. Chloramphenicol acted for long enough to ensure similar effects to persistent storage in the kidney. In this experiment 10 micrograms ml-1 of 5-bromodeoxyuridine was added for 60 hours for all doses of chloramphenicol and to the control. When the tissue culture cells were exposed to increasing doses, increased numbers of sister chromatid exchanges developed. Differences were significantly different to the control. PMID- 1585082 TI - Pathogenicity of Fusobacterium necrophorum biovar B. AB - Previous studies showed that the high minimum infective dose (more than 10(6) organisms) of biovar A strains of Fusobacterium necrophorum for mice by subcutaneous inoculation could be greatly reduced, often to less than 10 organisms, by suspending the fusobacteria in sublethal doses of broth cultures of certain other bacterial species, such as Staphylococcus aureus. The present study showed that no such enhancement of infectivity occurred with two biovar B strains. This observation, together with the low pathogenicity of pure cultures of these strains for mice, suggests that biovar B plays no more than a minor role in the aetiology of necrobacillosis. PMID- 1585083 TI - Further observations on the weak immunogenicity of Fusobacterium necrophorum. AB - Five virulent strains of Fusobacterium necrophorum resembled a single strain examined earlier by possessing little or no immunogenicity: severe subcutaneous infections cured with metronidazole failed to increase the resistance of mice to subcutaneous challenge 22 days after the cessation of treatment. PMID- 1585084 TI - Confirmation of assignment of the bovine K-casein locus by PCR. AB - The provision of a bovine gene map will allow the ready identification of genetic disease in cattle and will lead to the identification of the genetic loci responsible for quantitative traits of economic importance. An extension of the polymerase chain reaction to the identification of linkage in bovine-Chinese hamster cell hybrids has improved the speed and facility of the assignment of genes to linkage groups and thus makes it easier to achieve a bovine linkage map. PMID- 1585085 TI - Chronic sorrow: a lifespan concept. AB - Losses are an integral part of chronic illness and disability. The term chronic sorrow, has been used to describe the long-term periodic sadness the chronically ill and their caregivers experience in reaction to continual losses. In this conceptual analysis of chronic sorrow, identified critical attributes are: cyclic sadness over time in a situation with no predictable end; external and internal stimuli triggering the feelings of loss, disappointment, and fear; and, progression and intensification of the sadness or sorrow years after the initial disappointment or loss. Model, borderline, related, contrary, and illegitimate cases illustrate what the concept is and what it is not. The meaning of chronic sorrow is compared to the meaning of unresolvable grief and depression. Chronic sorrow in various stages of life is illustrated in descriptions of: the situation and feelings of parents of handicapped children; multiple sclerosis patients in the middle, productive years; and elderly caregivers of spouses with dementia. Implications for research include the need to study the concept in various populations to determine its prevalence and operation. Through research, the meaning of the concept can be further clarified. This is a beginning step toward developing nursing theory that will give direction for providing care to persons encountering sadness over long periods of time. PMID- 1585086 TI - Quantification of the effects of listening to music as a noninvasive method of pain control. AB - This study quantified the effects of listening to music as a noninvasive nursing method of pain control. The effects of soothing and stimulating music on pain and tactile thresholds, heart rate, and blood pressure were determined on healthy female volunteers (N = 10) in a laboratory setting. Data were analyzed by ANOVA for repeated measures and post hoc comparison tests. Soothing music significantly elevated pain thresholds but not tactile thresholds. Stimulating music significantly elevated pain thresholds as well as tactile thresholds. Neither stimulating nor soothing music had a significant effect on autonomic activity. Based on the results of this laboratory study and other studies, the effects of listening to music on people in pain warrants further examination. PMID- 1585087 TI - A critical review of prenatal attachment research. AB - Prenatal attachment is a construct not only intriguing for nurse researchers, but also the object of attention from the lay public and popular media. Promoting prenatal attachment is assumed to have benefits particularly for children. Pregnant women are admonished that development of a successful mother-child relationship begins before birth and is their responsibility. The prenatal attachment research literature was reviewed to determine if the last statement could be supported. The current state of this body of literature is presented in this article along with a critique of the research studies and suggestions for future research. PMID- 1585088 TI - A description of the nature and dynamics of coping following coronary artery bypass surgery. AB - The purpose of this study was to explore the nature and dynamics of coping following coronary artery bypass surgery (CABS). The coping strategies of 129 subjects recovering from (CABS) were assessed at 1 and 6 weeks following surgery using the Revised Ways of Coping Checklist. The most frequently used coping strategy was seeks social support, followed, in descending order of frequency, by problem focused coping and the emotion-focused coping strategies of blamed self, wishful thinking, and avoidance. There was an overall decrease in coping between 1 and 6 weeks following CABS. Seeks social support, blamed self, and wishful thinking coping were used significantly less frequently at 6 weeks than at 1 week following CABS. The decreases in problem focused and avoidance coping, however, were not statistically significant. This study provides insight into the process of coping following CABS and supports the need for development of nursing strategies to promote coping in this population. PMID- 1585089 TI - [Expert in public health. Interview by Claire Manicot]. PMID- 1585090 TI - [Psychiatry on the couch of ethics]. PMID- 1585091 TI - [A law ill received by all]. PMID- 1585092 TI - [A fighter nurse. Interview by Claire Manicot]. PMID- 1585093 TI - [In Toulouse, a health community of great progress]. PMID- 1585094 TI - [Marc Livet: "the uneasiness remains"]. PMID- 1585096 TI - [Accidents due to cold exposure]. PMID- 1585095 TI - ["1992, the year of the new nurses"]. PMID- 1585097 TI - [The care of frostbite]. PMID- 1585098 TI - [Skiing accidents]. PMID- 1585099 TI - [The dangers of sports doping]. PMID- 1585100 TI - [Prevention of hypothermia in the food industry]. PMID- 1585101 TI - [Sexual disorders in the health care relation]. PMID- 1585102 TI - [Jean-Michel Belorgey: "We could have done better". Interview by Veronique Blocquaux]. PMID- 1585103 TI - [A safe voyage for all]. PMID- 1585104 TI - [Anne, nursing student in Chad. Interview by Claire Manicot]. PMID- 1585105 TI - [The conjured away death]. PMID- 1585107 TI - [Clinical trials in oncology]. PMID- 1585106 TI - [Clinical nurse researcher in oncology]. PMID- 1585108 TI - [Nurses with health volunteers]. PMID- 1585109 TI - [Nursing research ... desperately]. PMID- 1585110 TI - [Between laboratory and hospital]. PMID- 1585111 TI - [Labor unions]. PMID- 1585112 TI - [Intrauterine growth retardation]. PMID- 1585113 TI - [Stomatherapy care in a child with a gastrostomy]. PMID- 1585114 TI - [Letter of job application]. PMID- 1585115 TI - [When love is a game of improvisation ...]. PMID- 1585116 TI - [The means for preventing nosocomial infection (I)]. PMID- 1585117 TI - [Diabetes and education for health]. PMID- 1585118 TI - [Arrhythmias in the ICU]. PMID- 1585119 TI - [Teaching self-care, a key task of nursing]. PMID- 1585120 TI - [Delivery with epidural anesthesia (I)]. PMID- 1585121 TI - [The tuberculin test]. PMID- 1585122 TI - [The nursing consult in dietetics and nutrition (I). The Primary Care Center of Numancia de Barcelona]. PMID- 1585124 TI - [Continuing education. 69. The care of the neurosurgery trauma patient]. PMID- 1585123 TI - [Hospital beds for general use]. PMID- 1585125 TI - Coupler-related real ear gain. Interaction between subject and hearing aid type. AB - In order to select hearing aids with a highly predictable real ear gain, in situ gain and compliance through the individual ear mould were measured on 8 normal hearing subjects. The latter were chosen in order to reduce gain variation caused by various pathological conditions of the ear. All behind-the-ear aids commonly used in Sweden and one in-the-ear aid were studied. One sample of each hearing aid type was tested and the subjects had identical ear moulds. Hence, the variables were hearing aid type and subject. The study showed wide intra-subject coupler-related real ear gain variation (30 dB). Most of the aids showed a distinct correlation between coupler-related overall gain, and mould compliance. Some of the aids gave more uniform real ear gain, i.e. low interaction between subject and frequency-dependent gain. These results are elucidated by measuring the aid's acoustic output impedance. PMID- 1585126 TI - Comparison of certain measures of speech and noise level. AB - Four different methods of measuring speech and noise level in speech audiometry are compared. The methods differ with regard to the temporal characteristic of the integrator used for determining the level. The four methods are characterized by their so-called detector/indicator characteristics, being 'fast', 'slow', 'impulse', and long-term integration. It is concluded that the method using long term integration is preferable. If the speech material consists of short speech segments such as isolated words separated by pauses, the long-term rms level should be measured without integrating over the pauses between the speech segments. PMID- 1585127 TI - Psychoacoustical tuning curves. Normative data for clinical use. AB - This normative study presents a clinically applicable method with which to obtain Psychoacoustical Tuning Curves: data are obtained with clinical audiometers, and measurements are performed on normal-hearing non-trained volunteers. A simultaneous masking method with test frequency of 4,000 Hz was used, withmasking being incremented in 5 dB or 1 dB steps. One group of subjects was tested three times with 5 dB incrementing steps to evaluate the method's reproducibility. A second group of subjects was measured twice with 1 dB incrementing steps, to compare the reproducibility of the 1-dB step measurements, and the difference between the 1-dB step and 5-dB step measurements. All the data were evaluated as normative values. The method presented proves to have a good reproducibility. Although testing with 1-dB incrementing steps provides more accurate measurements and curves with steeper slopes, the 5-dB incrementing step method is more practicable. Interest variability evaluation indicates that differences between two measurements performed on the same person exceeding 120 Hz (2 SD) bandwidth can be interpreted as significant. PMID- 1585128 TI - High-frequency audiometry. Masking in electric bone-conduction audiometry. AB - Recently, the 'electric bone-conduction' (EBC) audiometer (Audimax 500) has been used to measure high-frequency (HF) hearing. With this audiometer stimulation is binaural. No commercial masking method was available. In this study, white noise from a Madsen OB822 audiometer and presented via Sony MDR-V4 dynamic earphones, was used for masking. The masking and cross-hearing effect was measured in 8 unilaterally deaf subjects and the masking procedure was tested with 104 young normal-hearing subjects. The results showed that the EBC signals can be masked with air-conduction signals, and thus, the EBC measurements reflect monaural thresholds. The minimum masking level was 50-60 dB SPL in the HF range. There were no cross-hearing problems in the HF range with the earphones used. At the frequencies 0.5-14 kHz, the better ear's masked EBC thresholds were on the average 2.6 dB (range 0-4.5 dB) poorer, compared with the binaural EBC thresholds, indicating a binaural summation effect. PMID- 1585129 TI - Simple discrimination isn't really simple. A confirmatory analysis of the Speech Sound Pattern Discrimination Test. AB - This paper reports the results of a componential analysis of items comprising the Speech Sound Pattern Discrimination Test (SSPDT). The SSPDT, developed by Bochner et al. (1986), uses a closed-set sentence discrimination task to assess the auditory speech processing skill of severely and profoundly hearing-impaired individuals. A set of components reflecting differences in the phonetic and task related characteristics of the test stimuli was developed, and the contributions of the components to discrimination task difficulty were evaluated using linear regression methodology. Discrimination task difficulty indices were transformations of percent-correct scores, resulting from fit of the SSPDT data to the Rasch measurement model. Three of the hypothesized components (one spectral, one temporal, and one task-related) entered a stepwise regression solution. These components have an intrinsic role in the construct validity of the instrument. The structure of the discrimination task, however, is more complex than might be suspected, because 'same' or matching test stimuli showed advantages in ease of discriminability compared with their 'different' or non matching counterparts. The study findings will facilitate development of an enlarged item bank, and aid in the interpretation of test scores. PMID- 1585130 TI - Clinical reliability of insertion gain measurements with assistive listening devices. AB - Real ear insertion gain was measured in 14 persons fitted with a variety of common assistive listening devices. Measurements were made in a quiet, but not soundproofed, clinical environment. The reliability of such insertion gain measures was studied, both for short-term and long-term test-retest conditions. The results indicated that insertion gain measurement of assistive listening devices can be performed as a routine clinical procedure. Intrasubject standard deviations were comparable in most cases to those clinically obtained using hearing aids with custom ear moulds. PMID- 1585131 TI - A long-term observation of spontaneous oto-acoustic emissions (SOAEs). AB - In a follow-up study of 22 ears made after a mean interval of 68 months, spontaneous oto-acoustic emissions (SOAEs) showed marked changes. At follow-up visits, fewer SOAEs were recorded than at the first examination. As the set-up employed at follow-ups was much more sensitive, this observation gains even more weight, because--given identical cochlear structures--a greater number of SOAEs ought to have been recorded. In analogy to age-related high-frequency hearing loss, SOAEs recorded at the follow-up examination were found at lower frequencies. This was associated with yet another phenomenon: Precise frequency data (derived from a 4,000 line spectrum) available for 13 SOAEs (7 subjects) from the first examination showed that SOAE frequencies had dropped slightly in all subjects. In 5 of them the frequency drop was significant (p less than 1/1000 in each case). PMID- 1585132 TI - Hearing instruments for the elderly hearing impaired. PMID- 1585134 TI - The new medical education at the Faculty of Health Sciences, Linkoping University -a challenge for both students and teachers. AB - The medical faculty at the Linkoping University was established in 1970. Until 1986 the medical students spent their first two preclinical years in Uppsala and the last three and a half years in Linkoping following a conventional medical curriculum. In the fall of 1986 the Health University (Faculty of Health Sciences) was established with a common organization and educational aims i.e. problem-based learning and multiprofessional education for six health educations, physicians, nurses, physioterapists, occupational therapists, laboratory technologists and community care managers. The medical education in Linkoping then became complete with a thorough innovation of the curriculum. The first students following the new curriculum will have their final examinations in January 1992. The experiences of teachers and students are overwhelmingly positive as shown in an evaluation from the other five health curricula of shorter duration. Since no medical students have so far completed their studies according to the new curriculum no corresponding evaluation for the medical education is yet available. However, the author here describes his experiences in the new role as tutor and examiner. PMID- 1585133 TI - Daily impedance audiometric screening of children. Validity of impedance tympanoscope ZS331 compared with impedance audiometer AZ7. AB - The purpose of the present study was to test a fully automated screening impedance tympanoscope against a clinical impedance audiometer. Previous studies have indicated a relatively high incidence of type B tympanograms when using the tympanoscope and in addition shown a surprisingly large number of type B curves of one day's duration. The present study was based on 51 otherwise healthy children attending kindergartens (100 ears) who underwent daily tympanometric screening with both the impedance tympanoscope ZS331 and the impedance audiometer AZ7. The tympanoscope indicated a significantly larger number of type B tympanograms, and in 16 cases the type B curves could be demonstrated on only one day, resulting in significantly higher point and period prevalences of type B tympanograms. The difference is mainly attributable to the different ways in which a type B tympanogram is defined by the two instruments. On the basis of the present study we conclude that the impedance tympanoscope is not well suited for this type of study. PMID- 1585135 TI - Socio-economic factors and feto-infant mortality. AB - During this century, improvements in fetal and infant mortality have been dramatic in the western world, mainly as a result of improved socio-economic conditions. Relative to many other developed countries, the decrease has been more dramatic in the Nordic countries. Population-based health registries exist in all Nordic countries. By record-linkage between birth registries and census data, it is possible to perform population-based studies on the association between social factors and feto-infant mortality. Such studies have recently been carried out in Denmark, Finland, Norway and Sweden and socio-economic differences in late fetal and postneonatal death rates were seen. Death rates as well as the relative importance of socio-economic factors differed between these countries. In Norway, infants delivered by women with 9 years or less of schooling faced an almost three-fold increased risk of dying postneonatally as compared to infants delivered by women with at least 12 years of education. In order to successfully decrease the socio-economic differences in feto-infant mortality between and within the Nordic countries, it is necessary to analyse possible preventable risk factors that are distributed unevenly not only in different socio-economic groups but also between the Nordic countries. PMID- 1585136 TI - Unemployment and cardiovascular risk indicators. Data from the MONICA survey in northern Sweden. AB - We studied the effect of unemployment, or the threat of unemployment, on indicators of cardiovascular risk in a randomly selected cross-sectional sample of the population aged 25-64 years in northern Sweden with interviews and a health examination. In men, unemployment for more than one year correlated significantly with systolic blood pressure, serum cholesterol level, HDL quotients, cigarette smoking and physical inactivity. In women, unemployment correlated significantly with body mass index, HDL-quotient, cigarette smoking and physical inactivity. Our results support the hypothesis that correlations between unemployment and cardiovascular disease found in other studies could be partly explained by elevated risk indicators due to unemployment. PMID- 1585137 TI - The HIV pandemic in Sweden: what do people really think about mandatory HIV testing? AB - This study examines (1) how the general population of Sweden defines the concept of mandatory HIV testing; (2) what measures people consider should be taken against HIV infected individuals if mandatory testing is introduced; and (3) how the opinion of mandatory testing is affected if people consider the matter from a personal rather than neutral point of view. The two first questions were investigated in personal interviews with 1651 randomly selected individuals aged 16-74 years (Study 1). The third question was investigated in an experimental study among Swedish college/university students (Study 2). A total of 58% of the respondents in Study 1 favoured mandatory HIV testing. Confronted with a situation where mandatory testing is introduced and someone refuses to take a test 40% favoured forced testing and 24% favoured fines. If someone is identified as being HIV infected three out of four recommended action only in case this person exposes others to risk. In Study 2 mandatory testing was not, as could be expected, considered to be more repellent if the issue was viewed from a personal point of view than from a neutral one. PMID- 1585138 TI - Management of occupational risk to reproduction in a Danish county. AB - In Denmark pregnant women are entitled to receive maintenance allowances if the working conditions are suspected to be harmful to the fetus. The aim of the study was to evaluate these preventive measures taken to reduce occupational hazards to reproduction in Denmark. In 1985 1,247 pregnancies were identified in Ribe county during a 6-month period. Three hundred and forty-five women employed at the beginning of the pregnancy in manufacturing industries, construction work, health services, or agriculture were interviewed by telephone concerning their working conditions and the measures taken to reduce possible occupational risks. The response rate was 85%. On the basis of the interviews the risks and the preventive measures were assessed. Out of 200 women who had no changes in the working conditions during pregnancy, 46 (23%) had a working situation which was considered potentially harmful. For 57 the working situation was changed during the first months of pregnancy because of an assumed risk. The remaining 37 were out of work or received maintenance allowances because of occupational hazards. In this study a greater awareness than expected about possible occupational risks was found, but in some instances occupational risks were overlooked or neglected. PMID- 1585139 TI - Disability pensions due to musculo-skeletal disorders among men in heavy occupations. A case-control study. AB - The relative risk of disability pension due to musculo-skeletal disorders has been studied with regard to occupation and work load. The study population comprised men born 1915 to 1934, living in Stockholm county. 1307 men who received a disability pension during 1979, 1980, 1981 and 1984 due to disorders from the low back, neck/shoulder, hip, and knee were compared with 298 randomly selected men concerning occupation and occupational work load. Disability pensions were more common both in men with medium and high physical work load compared to men with low physical work load. Construction workers and metal workers had a high relative risks of receiving disability pensions because of disorders in all four body regions, and men in many other occupations had disorders in two or three regions. In office workers the risk of disability pension because of musculo-skeletal disorders was low. PMID- 1585140 TI - Stability of therapeutic alliance and its relationship to outcome in short-term inpatient psychiatric care. AB - The relationship of therapeutic alliance to patient and treatment characteristics and to outcome, was studied in a sample of 106 patients consecutively admitted to a short-term psychiatric ward. The main finding was that a better therapeutic alliance at discharge was related to a greater improvement in symptoms during treatment. A multivariate model for prediction of outcome revealed a significant contribution from therapeutic alliance at discharge but not from alliance at admission or from changes in alliance during treatment. Improvement in alliance was seen in 41.5% of the patients, no change in 28.3% and a deterioration in 30.2%. Patients who improved their alliance did not differ from the others in background characteristics, but were more often subject to psychopharmacological treatment and were more often treated in a basic activation group. Patients with a stable poor alliance more often stated physically oriented target complaints at admission while patients with a stable satisfactory alliance more often presented interpersonally related complaints. It is concluded that further research in the field would benefit from a closer description of the change in the alliance and its relationship to treatment characteristics and outcome. PMID- 1585141 TI - Differences in height between socially more and less privileged 10 year old Stockholm children born in 1933-1963. AB - The change of the difference in height between two socially extreme groups of 10 year old Stockholm children born in 1933, 1943, 1953 and 1963 was analysed. Data on height and social conditions were taken from the school health records. The two groups were established on the basis of the father's occupation and the number of children in the family. The height of the 10 year old children in the more privileged group born in 1933, 1943 and 1953 was virtually unchanged, but the height in the less privileged group increased gradually. The difference between the two groups was levelled out in the 1953 cohort. However, it reappeared in the 1963 cohort, mainly as a result of increasing height in the more privileged group and fairly unchanged height in the less privileged group. PMID- 1585142 TI - Relative survival of terminal cancer patients in home versus hospital care. AB - A non-randomized study was undertaken in 1980-1982 to compare the effectiveness of home care versus hospital care for patients suffering from terminal stages of malignant diseases at a large cancer hospital in Pireaus, Greece and in the surrounding community. The survival pattern of 101 patients with malignant disease at various stages enrolled in a home care program for terminal patients was compared with the survival pattern of a matched comparison group of an equal number of hospital treated cancer patients. The two groups were matched for age, sex, time of initial diagnosis, primary tumor and stage of the disease at the time of diagnosis. The comparison of the survival curves was done using the logrank test taking into account censored observations. The results indicate that, under the conditions prevailing while this study was undertaken, home care was less effective compared to hospital care when survival was used as the only outcome criterion. PMID- 1585143 TI - Physicians and alternative medicine--an investigation of attitudes and practice. AB - In the present paper, the attitudes of three different groups of physicians toward treatment with alternative medicine have been investigated. One of the groups studied consisted of randomly selected licensed physicians from the Swedish National Board of Health and Welfare. The other two groups comprised two different associations of physicians involved with alternative medicine. One third of the former groups were positively disposed toward one or more of the alternative medical technologies, while the latter groups were more positive toward alternative medicine in general. Attitudes, along with motives for such interest, varied depending on the orientations of the different interest groups. The most common motives for expressing interest in alternative medicine included a feeling of clinical powerlessness in the face of certain problems for which patients consult a physician, and a dissatisfaction with the scientific approach of academic medicine. A minority stated that their interest in alternative medicine pre-dated their medical education. Physicians' interest in alternative medicine can be understood both as a critical reaction to academic medicine and as evidence that some alternative medical technologies are effective. Hence there is a need to determine whether there are shortcomings to be found in academic medical education and scientific ideals, and also to assess alternative medical technologies at regular intervals. PMID- 1585144 TI - Reflecting differences. Health care begins to address needs of women and minorities. PMID- 1585145 TI - Pointing Fingers. DNA identification is called into question. PMID- 1585146 TI - Trojan horse. Did a protective peptide exacerbate Bhopal injuries? PMID- 1585147 TI - Women and AIDS. PMID- 1585148 TI - Genes to order. PMID- 1585149 TI - The mice that missed. PMID- 1585150 TI - Control of rabies in wildlife. PMID- 1585151 TI - Accounting for environmental assets. AB - A country can cut down its forests, erode its soils, pollute its aquifers and hunt its wildlife and fisheries to extinction, but its measured income is not affected as these assets disappear. Impoverishment is taken for progress. PMID- 1585152 TI - [Transvaginal Doppler study of embryonic heart action in early pregnancy]. AB - Embryonic cardiac activity was observed by means of transvaginal Doppler ultrasound in a period from the 28th through the 78th day after conception (p. c.). We were able to detect a correlation between the embryonic heart rate and the stage of pregnancy as well as a correlation to the crown-rump length. The maternal age did not seem to have any effect on the appearance of embryonic heart activity. The number of registered Doppler echoes did not yield information on embryonic heart development. PMID- 1585153 TI - [What is the contribution of Doppler sonography of the umbilical artery in diagnosis of intrauterine growth retardation?]. AB - Pulsed Dopplersonography of the umbilical artery was performed in 155 singleton high-risk pregnancies without malformations or chromosomal abnormalities. 59 foetuses were classified as foetuses with intrauterine growth retardation (IUGR). 46 of them had a birth weight below the tenth percentile. In 20 cases the pulsatility index (PI) was elevated (sensitivity: 44%). In all there were 50 neonates with a birth weight below the tenth percentile, 46 of whom were detected by biometry (sensitivity: 92%). 8 dystrophic neonates with a biometry that revealed IUGR were compromised by perinatal asphyxia. In six cases operative delivery was necessary and two cases with reversed diastolic flow ended in intrauterine foetal death. 7 of those foetuses had an elevated PI. The sensitivity of Dopplersonography in this group was 88%, the negative predictive value 97%. The positive predictive value with regard to a dystrophic neonate can be improved from 78% to 91%, if compared with biometry alone. Summing up, Dopplersonography of the umbilical artery can distinguish very well between IUGR foetuses at risk of perinatal morbidity or mortality and those IUGR foetuses with sufficient placental circulation who are, therefore, not at risk. PMID- 1585154 TI - [Comparative studies of the uterine cervix in pregnancy using palpation and vaginal sonography]. AB - Ultrasonography and manual palpation were used to evaluate the uterine cervix of 71 pregnant women between 14th and 36th week of gestational age. The sonographic length of the uterine cervix was about 4.2 cm according to the relevant cervix palpation (Group I), about 3.2 cm in the moderately shortened cervix (Group II) and about 2.8 cm in the severely shortened cervix (Group III). The distance between the surface of the ectocervix to the urinary bladder corresponded to the cervical palpation showing a constant difference of about 0.5 cm. No difference could be found in the width of the upper cervix. The index was determined as ratio of the sonographically ascertained cervical length and width of the supravaginal cervix. A value of 0.8 or lower describes a cervical incompetence of a higher degree and signifies an unfavourable prognosis. The evaluation of cervical incompetence and the relevance of the sonographically detected opened internal os have not yet been clarified. A hitherto unsolved problem is the dilatation of the cervical canal in case of immature palpatory findings with traumatic anamnesis. PMID- 1585155 TI - [Cephalic index: a neglected parameter of standard fetal biometry]. AB - From 1.1.1990 to 15.3.1991, in 1074 women between the 13th and 40th weeks of pregnancy, the biparietal diameter (BIP), fronto-occipital diameter (FOD) and kephalic index (KI = BIP/FOD) were measured. The median of the kephalic index varied between 0.81 and 0.84 during different pregnancy weeks, with a range between 0.67 and 1.00. Correction to normokephaly (KI = 0.84) produced differences of up to 10 mm to measured values of BIP. We believe it necessary to determine the kephalic index in each kephalometry and to correct the measured value of BIP at least in those cases where the measured kephalic index differs significantly from normokephaly (KI = 0.84). PMID- 1585156 TI - [Abdominal, perineal and vaginal sonographic diagnosis of cervix insufficiency]. AB - In patients with cervical incompetence, the diagnostic efficiency of abdominal, perineal and vaginal sonography was compared. 73 patients, who were divided into three groups, were examined: Group A (n = 50) control group, Group B (n = 11) normal pregnancies, Group C (n = 12) pregnancies with demonstrated cervical incompetence. According to our results, using vaginal sonography, only the incompetent pregnancies showed significant shortening of the cervical length. Characteristic scans were also obtained (membrane herniation) which were useful in diagnosis and control in the performance of cerclage. PMID- 1585157 TI - [Sonographic structural analysis of the Achilles tendon and biomechanical implications]. AB - Ruptures of the Achilles tendon mainly occur on the ground of predisposing destruction of tendon structure. The aim of this retrospective US study was to evaluate the location and extent of tendon abnormalities. 62 patients (49 male, 13 female; 19 to 57 years, mean 38) with achillodynia of short duration and/or clinically suspected tendon abnormalities were evaluated sonographically. Together with a review of the literature, US findings (location, extent, and echo pattern) were compared with clinical findings. With US, abnormalities could be detected with a sensitivity of 0,76 and a specificity of 0.9. Pathologic lesions could be grouped as follows: (1) pain without any clinical signs or US findings (tenalgia); (2) nodular tendinitis which in 52% appeared in the form of a tiny hypoechoic lesion in the ventromedial part of the tendon 2-3 cm proximal to the os calcis; (3) peritendinal oedema; (4) circumscribed tendon swelling, (5) extensive inhomogeneities of tendon structure. With US, abnormalities of the Achilles tendon may be detected at an early stage of the disease and hence the risk of tendon rupture may be predicted to better advantage. PMID- 1585158 TI - [Extended diagnosis of color-coded Duplex sonography by ultrasound contrast media. Imaging of movements of the urinary tract and tubes in animal experiment]. AB - In colour-coded Duplex sonography, ultrasound contrast agents produce a significant enhancement of Doppler signals from the blood. Animal experiments were performed to examine whether a combination of colour-coded Duplex sonography and ultrasound contrast agents can also visualise movements from hollow spaces which do not normally contain scatteres (or an insufficient number of them). The animal experiments showed that the method can visualise both movements in the tubae and a vesicoureteral reflux. This opens up new diagnostic possibilities for ultrasound, which, however, still require rechecking by means of clinical studies. PMID- 1585159 TI - [Initial results of a new method of sonographic diagnosis of lung maturity]. AB - The immaturity of the foetal lung is one of the central problems in obstetrics. In this paper first results are presented to determine the maturity of the foetal lung by sonography. Using the foetal liver as a reference organ we are avoiding the known pitfalls which made it impossible in the past to standardise the foetal lung changes depending upon the age of gestation. We examined 121 patients between week 27 and week 41. In one ultrasound section cut we depicted lung and liver as well. According to the known A-mode we registered frequencies in both organs. The registered frequencies were entered digitally into a computer and checked for f mean, f max and f min. Subsequently we calculated quotients of frequencies of the foetal lung and liver. For all weeks of gestation the mean value and standard deviation were calculated. We found that the liver is an adequate reference organ, since there is no change in the reflection pattern between the different weeks of gestation. We registered significant differences in the quotients of lung and liver between the different weeks of gestation, a cutting line being week 35. A quotient of Q mean lower than 1.1 hints to lung maturity while values over 1.1 point to immaturity. PMID- 1585160 TI - [Prenatal diagnosis of thanatophoric dwarfism]. AB - Thanatophoric dwarfism is a rare malformation, occurring in less than 1:10,000 pregnancies. It can be discovered by standard ultrasound examination, but other skeletal dysplasias such as achondroplasia, achondrogenesis and polydactyly syndromes must be taken into consideration. Sonographic findings are polyhydramnia, narrow chest, symmetric tetramicromelia and macrocephaly. Macrocephaly might cause a problem for vaginal delivery. The narrow chest with secondary lung hypoplasia determines the infaust prognosis. PMID- 1585161 TI - [The fetal brain in vaginal sonography]. AB - Transvaginal sonographic imaging of the fetal brain performed in the second and third trimester of pregnancy is presented. By this technique coronal and sagittal sections of the central nervous system can be obtained which are similar to those performed via cranial sonography postnatally. PMID- 1585162 TI - The state of South Dakota's child: 1991. AB - This annual report describes the continuing trend of a decreasing birth rate in South Dakota. Infant mortality data show that South Dakota's neonatal mortality rates continue to be below those of the nation and post neonatal mortality rates exceed those of the United States. A very high Native American post neonatal mortality rate persists. Low birth weight contributes to approximately three quarters of newborn deaths and has declined by approximately 1% over the past two and one half decades. Descriptions of preterm labor prevention programs are presented with an emphasis upon the need for education of pregnant women and communities about its risk factors and warning signs. A review of a variety of new programs that aim to improve maternal and child health in South Dakota is provided. PMID- 1585163 TI - Ethics for the surgeon. AB - Guidelines are helpful in analyzing the process of ethical behavior in the surgical arena. In this paper, three guidelines will be considered: Action, Disposition, and Structure. Action deals with the surgeon's conduct relative to ethical principles. Disposition refers to the character of the surgeon; and virtues relevant to character are considered. Structure is the environment in which medical treatment and diagnosis takes place. Relative to these above guidelines, the case of a 79 year old lady with a fractured hip is discussed. PMID- 1585164 TI - Where is the waste in medical waste? PMID- 1585165 TI - Hand lacerations of the combined interdigital-intermetacarpal region (split hand). AB - Longitudinal lacerations involving the finger commissures and adjacent intermetacarpal clefts (including the adjacent tendons, the intrinsic muscles, the deep transverse metacarpal ligament, adjacent arteries, nerves, bones and joints), present multiple problems not seen in the unusual hand lacerations. Thorough cleansing, delayed closure, accurate repair of all injured structures with prompt appropriate rehabilitation results in excellent appearance and early function. PMID- 1585166 TI - Early detection of adolescent mood disorders. AB - Adolescent depression remains significantly underdiagnosed despite its official recognition since 1975 and its association with high morbidity and mortality. With the exception of teachers, physicians are the professionals most likely to see depressed youngsters. This article attempts to increase the physician's awareness of adolescent depression. PMID- 1585167 TI - DNA fingerprinting and eyewitness testimony. PMID- 1585168 TI - Eggs-actly. AB - In Daniel E. Koshland, Jr.'s editorial "Methodology and theory at the frontier" (27 Mar., p. 1621), the name of the Thomson atom was spelled incorrectly. PMID- 1585169 TI - NIH leak policy honored in the breach. PMID- 1585170 TI - A shaky consensus on misconduct. PMID- 1585171 TI - Intellectual property. A new wrinkle in Retin-A dispute. PMID- 1585172 TI - Biotechnology. Swiss drug giants seek antidote to activists. PMID- 1585173 TI - Up close and personal with DNA. PMID- 1585174 TI - The early evolution of eukaryotes: a geological perspective. AB - Molecular phylogenies of eukaryotic organisms imply patterns of biological and environmental history that can be tested against the geological record. As predicted by sequence comparisons, Precambrian rocks show evidence of episodic increases in biological diversity and atmospheric oxygen concentrations. Nonetheless, complete integration of the two records remains elusive and may require that the earliest macroscopic organisms be recognized as extinct experiments in eukaryotic multicellularity. PMID- 1585175 TI - Solution structure of a calmodulin-target peptide complex by multidimensional NMR. AB - The three-dimensional solution structure of the complex between calcium-bound calmodulin (Ca(2+)-CaM) and a 26-residue synthetic peptide comprising the CaM binding domain (residues 577 to 602) of skeletal muscle myosin light chain kinase, has been determined using multidimensional heteronuclear filtered and separated nuclear magnetic resonance spectroscopy. The two domains of CaM (residues 6 to 73 and 83 to 146) remain essentially unchanged upon complexation. The long central helix (residues 65 to 93), however, which connects the two domains in the crystal structure of Ca(2+)-CaM, is disrupted into two helices connected by a long flexible loop (residues 74 to 82), thereby enabling the two domains to clamp residues 3 to 21 of the bound peptide, which adopt a helical conformation. The overall structure of the complex is globular, approximating an ellipsoid of dimensions 47 by 32 by 30 angstroms. The helical peptide is located in a hydrophobic channel that passes through the center of the ellipsoid at an angle of approximately 45 degrees with its long axis. The complex is mainly stabilized by hydrophobic interactions which, from the CaM side, involve an unusually large number of methionines. Key residues of the peptide are Trp4 and Phe17, which serve to anchor the amino- and carboxyl-terminal halves of the peptide to the carboxyl- and amino-terminal domains of CaM, respectively. Sequence comparisons indicate that a number of peptides that bind CaM with high affinity share this common feature containing either aromatic residues or long chain hydrophobic ones separated by a stretch of 12 residues, suggesting that they interact with CaM in a similar manner. PMID- 1585176 TI - Modulation of an NCAM-related adhesion molecule with long-term synaptic plasticity in Aplysia. AB - A form of learning in the marine mollusk Aplysia, long-term sensitization of the gill- and siphon-withdrawal reflex, results in the formation of new synaptic connections between the presynaptic siphon sensory neurons and their target cells. These structural changes can be mimicked, when the cells are maintained in culture, by application of serotonin, an endogenous facilitating neurotransmitter in Aplysia. A group of cell surface proteins, designated Aplysia cell adhesion molecules (apCAM's) was down-regulated in the sensory neurons in response to serotonin. The deduced amino acid sequence obtained from complementary DNA clones indicated that the apCAM's are a family of proteins that seem to arise from a single gene. The apCAM's are members of the immunoglobulin class of cell adhesion molecules and resemble two neural cell adhesion molecules, NCAM and fasciclin II. In addition to regulating newly synthesized apCAM, serotonin also altered the amount of preexisting apCAM on the cell surface of the presynaptic sensory neurons. By contrast, the apCAM on the surface of the postsynaptic motor neuron was not modulated by serotonin. This rapid, transmitter-mediated down-regulation of a cell adhesion molecule in the sensory neurons may be one of the early molecular changes in long-term synaptic facilitation. PMID- 1585177 TI - Serotonin-mediated endocytosis of apCAM: an early step of learning-related synaptic growth in Aplysia. AB - The long-term facilitation of synaptic efficacy that is induced by serotonin in dissociated cell cultures of sensory and motor neurons of Aplysia is accompanied by the growth of new synaptic connections. This growth is associated with a down regulation in the sensory neuron of Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this down-regulation, thin-section electron microscopy was combined with immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM. Within 1 hour, serotonin led to a 50% decrease in the density of gold-labeled complexes at the surface membrane of the sensory neuron. This down-regulation was achieved by a heterologous, protein synthesis-dependent activation of the endosomal pathway, which leads to internalization and apparent degradation of apCAM. The internalization is particularly prominent at sites where the processes of the sensory neurons contact one another and may act there to destabilize process-to-process contacts that normally inhibit growth. In turn, the endocytic activation may lead to a redistribution of membrane components to sites where new synapses form. PMID- 1585178 TI - Protein solvation in allosteric regulation: a water effect on hemoglobin. AB - The oxygen affinity of hemoglobin varies linearly with the chemical potential of water in the bathing medium, as seen from the osmotic effect of several neutral solutes, namely sucrose, stachyose, and two polyethyleneglycols (molecular weights of 150 and 400). The data, analyzed either by Wyman linkage equations or by Gibbs-Duhem relations, show that approximately 60 extra water molecules bind to hemoglobin during the transition from the fully deoxygenated tense (T) state to the fully oxygenated relaxed (R) state. This number, independent of the nature of the solute, agrees with the difference in water-accessible surface areas previously computed for the two conformations. The work of solvation in allosteric regulation can no longer go unrecognized. PMID- 1585179 TI - An origin of DNA replication and a transcription silencer require a common element. AB - A eukaryotic chromosomal origin of replication was identified in the yeast Saccharomyces cerevisiae. By several criteria, including map position, deletion analysis, and a synthetic form of saturation mutagenesis, the origin co-localized with the HMR-E silencer, which is a DNA element that represses transcription of the adjacent genes. A specific site within the silencer was required for both initiation of chromosomal replication and for repression of transcription. This analysis directly demonstrates that initiation of eukaryotic chromosomal replication is dependent on specific sequence elements and that a particular element can act in both initiation of chromosomal replication and regulation of transcription. PMID- 1585180 TI - Cloning and expression in yeast of a plant potassium ion transport system. AB - A membrane polypeptide involved in K+ transport in a higher plant was cloned by complementation of a yeast mutant defective in K+ uptake with a complementary DNA library from Arabidopsis thaliana. A 2.65-kilobase complementary DNA conferred ability to grow on media with K+ concentration in the micromolar range and to absorb K+ (or 86Rb+) at rates similar to those in wild-type yeast. The predicted amino acid sequence (838 amino acids) has three domains: a channel-forming region homologous to animal K+ channels, a cyclic nucleotide-binding site, and an ankyrin-like region. PMID- 1585181 TI - DNA hydrolyzing autoantibodies. AB - A DNA-nicking activity was detected in the sera of patients with various autoimmune pathologies and was shown to be a property of autoantibodies. The DNA hydrolyzing activity, which was purified by affinity and high-performance liquid chromatography, corresponded in size to immunoglobulin M (IgM) and IgG and had a positive response to antibodies to human IgG. The DNA hydrolyzing autoantibodies were stable to acid shock and yielded a DNA degradation pattern that was different from that of deoxyribonuclease (DNase) I and blood DNase. PMID- 1585182 TI - Occurrence of sialic acids in Drosophila melanogaster. AB - Sialylated oligosaccharides, which are cell type-specific and developmentally regulated, have been implicated in a variety of complex biological events. Their broad functional importance is reflected by their presence in a wide variety of phyla extending from Echinodermata through higher vertebrates. Here, sialic acids are detected throughout development in an insect, Drosophila. Homopolymers of alpha 2,8-linked sialic acid, polysialic acid, are developmentally regulated and only expressed during early Drosophila development. PMID- 1585183 TI - Modality-specific retrograde amnesia of fear. AB - Emotional responses such as fear are rapidly acquired through classical conditioning. This report examines the neural substrate underlying memory of acquired fear. Rats were classically conditioned to fear both tone and context through the use of aversive foot shocks. Lesions were made in the hippocampus either 1, 7, 14, or 28 days after training. Contextual fear was abolished in the rats that received lesions 1 day after fear conditioning. However, rats for which the interval between learning and hippocampal lesions was longer retained significant contextual fear memory. In the same animals, lesions did not affect fear response to the tone at any time. These results indicate that fear memory is not a single process and that the hippocampus may have a time-limited role in associative fear memories evoked by polymodal (contextual) but not unimodal (tone) sensory stimuli. PMID- 1585184 TI - [Osteoporosis]. PMID- 1585185 TI - [Fatty meat--fatty people]. PMID- 1585186 TI - [Induced sterilization and ethics]. PMID- 1585187 TI - [Man, a being in the planning stage]. PMID- 1585188 TI - [The prevention of hospital infections in endoscopy units]. PMID- 1585189 TI - [The preoperative preparation of the patient and the prevention of infection]. PMID- 1585190 TI - [The Portuguese Association of the Families and Friends of Alzheimer Patients]. PMID- 1585191 TI - [New support for the ailing heart]. PMID- 1585192 TI - [Creutzfeldt-Jakob disease]. PMID- 1585193 TI - [A pastoral letter on health in Portugal in the last 10 years from 1981 to 1991]. PMID- 1585194 TI - Magic lessons: rated R. PMID- 1585195 TI - From sow's ear to doctor. PMID- 1585196 TI - Seroprevalence of human immunodeficiency virus among adolescent attendees of Mississippi sexually transmitted disease clinics: a rural epidemic. AB - Human immunodeficiency virus (HIV) infection among adolescents is causing increasing concern, and teenagers attending sexually transmitted disease (STD) clinics run a high risk of contracting it. To determine the status of HIV infection in a Mississippi adolescent population, we evaluated seroprevalence rates for adolescents attending Mississippi State Department of Health STD clinics from 1988 to 1990. During this 2-year period, 9855 adolescents (aged 13 to 20 years) attended STD clinics, and HIV antibody was confirmed in 39 (seroprevalence rate 4.0/1000; 95% confidence interval [CI] 2.7 to 5.2). Seropositive rates were almost equal for male and female subjects (4.1/1000 and 3.8/1000, respectively), suggesting predominantly heterosexual transmission. Rates among blacks were 3.5 times higher than among whites. Adolescents with HIV infection were identified throughout the state, irrespective of urban centers. Rates among the smallest counties (ie, population less than 25,000) were not significantly different from those of the largest counties (ie, population greater than 100,000). Mississippi's rank in the top 10 states for other STDs and the state's high teenage pregnancy rate make it an epicenter of the HIV epidemic among adolescents. PMID- 1585198 TI - Anesthetic considerations for electroconvulsive therapy. AB - Electrically induced seizures have been used widely to treat psychiatric disease since their introduction in 1938. Seizure activity is the therapeutic aspect of this form of treatment, but it is accompanied by untoward physiologic consequences. Cardiovascular responses consist of generalized autonomic nervous system stimulation with initial parasympathetic outflow, followed immediately by a sympathetic response. In certain patients the sequence described may result in an initial bradycardia or even asystole, followed by tachycardia, dysrhythmia, and hypertension. The cerebrovascular system responds with a marked increase in cerebral blood flow in response to increased cerebral oxygen consumption, and dramatic elevation of intracranial pressure. General anesthesia for electroconvulsive therapy (ECT) must be administered only in locations equipped for support of the unconscious patient and treatment of complications. Intravenous access is mandatory in all patients, as is monitoring of blood pressure, and ECG, as well as pulse oximetry. Appropriate oxygen supplementation and ventilatory support are essential as they are during any procedure necessitating general anesthesia. Methohexital, 0.75 to 1.0 mg/kg intravenously, is the most frequently used agent for induction of anesthesia for ECT; muscle relaxation usually is accomplished with succinylcholine, 0.5 to 1.0 mg/kg. In patients at risk for ill effects from the tachycardia and hypertension that may accompany sympathetic nervous system response to ECT, nitroglycerin, propranolol, hydralazine, or other sympatholytic agents should be used to attenuate the potentially harmful sequelae of ECT. The efficacy of ECT requires a knowledge of anesthetic precepts, an understanding of the interaction between anesthetic drugs and seizure activity, and an awareness of the physiologic effects of ECT as well as the treatment of those effects. PMID- 1585197 TI - Health status of the aged: medical profile of a group of functional elderly. AB - By studying a group of very elderly but generally functional people, we have compiled a medical profile that helps describe health-related characteristics of effective aging. We obtained functional, nutritional, and biochemical information regarding 61 men and women (mean age 86.8 years) attending a veterans' convention. Twenty-three out of 60 (38%) reported a fall in the previous year, with those who were less physically active falling more than the most active. Many of the men were thin or had lost weight, but at most 3 of the 25 male subjects were clinically malnourished. Many of the women were heavy but were otherwise healthy. Of the 36 women, 6 (17%) had an elevated level of thyroid stimulating hormone (TSH). Five of 58 (9%) had low vitamin B12 levels. Even in the older old who seem to be aging well, falling is relatively common, and screening for certain laboratory abnormalities has a reasonably high yield. PMID- 1585199 TI - Attitudes and education of pediatric house staff concerning breast-feeding. AB - Pediatricians are expected to offer information and advice on breast-feeding to expectant and lactating mothers, but the educational experience for pediatric residents may not adequately prepare them for this responsibility. To examine knowledge and confidence regarding breast-feeding gained by pediatric house staff during their residency, a survey was administered to pediatric residents in a large, hospital-based training program. Of 108 program residents, 87 (81%) participated. Forty-one percent of the respondents were postgraduate level I (PL I), 29% were PL-II, and 30% were PL-III. There was no evidence that PL-III residents were more competent or comfortable with routine breast-feeding counseling or intervention than their PL-I counterparts. Residents who had breast fed, those with spouses who had breast-fed, and those with children of their own had the greatest knowledge and confidence base in several areas, such as their ability to teach breast-feeding techniques and to treat cracked nipples. They were also more familiar with different types of breastpumps. There were no significant differences among those who were or were not breast-fed as a child nor among men versus women. Residency programs must provide comprehensive education on breast-feeding to prepare future pediatricians to meet the needs of patients and their parents. PMID- 1585200 TI - Adolescent blood pressure survey: Tulsa, Oklahoma, 1987 to 1989. AB - The study goals were to document the incidence of elevated blood pressure (BP) values in public high school students in Tulsa, Oklahoma; to determine whether age and sex are risk factors; and to encourage adolescents with abnormal screening BP values to seek medical care. Over a 2-year period, 5537 adolescents aged 14 to 19 years were evaluated by a mass screening method. Blood pressure was measured once between 8:30 and 9:30 AM, with the students seated. Korotkoff phases 1 and 5 were recorded as systolic and diastolic BP. According to the criteria of the Second Task Force on Hypertension in Children and Adolescents, 334 students had elevated BP values (either systolic, diastolic, or both) (an incidence of 6%). Boys had an incidence of elevated systolic BP of 5.8%, while girls had a 2.8% incidence, a difference that might have been expected because of the generally higher incidence among men in the adult population. The incidence of elevated diastolic BP was 2.8% in boys and 2.1% in girls. Statistically significant differences between boys and girls mean systolic and diastolic elevations were found, but were not considered clinically significant. An instructional mailing was done in an effort to stimulate follow-up medical care for those with abnormal findings, but its effect was not measured. PMID- 1585201 TI - Integrating the cognitive mental status examination into the medical interview. AB - The frequency of cognitive deficits in medical patients makes the cognitive mental status evaluation an important component of the medical interview. This paper helps delineate the clinical situations in which formal cognitive mental status questioning is indicated. We address the critical issues involving the doctor-patient interaction in order to facilitate the evaluation of mental status without alienating the patient or introducing artificial and unnecessary questions. We review more specifically the areas of attention, memory, language, constructional ability, and higher cognitive functions. Finally, we address issues of referral for further evaluation. PMID- 1585202 TI - Perioperative complications of long-term central venous catheters in high-risk patients: predictors versus myths. AB - A prospective cohort of 126 patients having long-term central venous catheterization was collected over a 10-month period. The patients were preoperatively assessed for the following risk factors: previous catheter placement, an absolute neutrophil count less than 500/mm3, a platelet count less than 50,000/mm3, a BUN value greater than 60 mg/dL or a serum creatinine level greater than 2.5 mg/dL, a prothrombin time greater than 1.5 times control, recent sepsis, and a Western blot test positive for HIV. The incidence of perioperative complications was 23%. Complications included pneumothorax, arterial puncture, tunnel hematoma, unsuccessful initial placement, and reaction to local anesthesia or blood products. No single risk factor had any statistical significance in predicting a complication. In the subpopulation of patients having two or more risk factors, the complication rate was 50%, with the majority of these being failed placement attempts. We conclude that inserting a permanent central venous catheter is not a benign procedure, but it can be safely done in critically ill patients. Furthermore, evaluation of preoperative risk factors in candidates for catheterization can be helpful to the surgeon with respect to counseling and operative planning. PMID- 1585203 TI - Analysis of local recurrence of midrectal cancer after low anterior resection and stapled anastomosis. AB - We evaluated local recurrences of midrectal cancer in 33 patients treated with low anterior resection and stapled end-to-end anastomosis. All patients had follow-up for at least 2 years or until death. There were 21 men and 12 women. Data were analyzed with attention to Astler-Coller modified Dukes' stage, distal margin of resection, degree of histologic differentiation, location of the tumor, blood transfusion, and adjuvant therapy. Distal margin of resection, histologic differentiation, and location of the tumor had no prognostic significance regarding local recurrence. The use of adjuvant therapy remains controversial. The immunosuppressive effects of blood transfusion may affect local recurrence. Dukes' staging remains the standard for prognosis of recurrence in rectal cancer. PMID- 1585204 TI - Comprehensive surgical management of mandibular fractures. AB - Mandibular fractures are common facial injuries. Classifications are combined and correlated with specific treatment modalities. Combined classification of fractures indicates the difficulty of treatment required. Many surgical techniques have been used and accepted as proper methods for reduction and fixation of mandibular fractures. Most studies advocate one technique as superior to others. The range of procedures now available include observation, closed reduction with maxillomandibular fixation, transoral reduction, intraosseous wire fixation, miniplate rigid osseous fixation, compression rigid osseous fixation, and external skeletal fixation. Our evaluation of the specific advantages of each modality indicates that selection of a specific procedure is individualized according to combined classification of the mandibular fracture, the surgical procedure's advantages and disadvantages, the patient's desires, and the surgeon's ability and clinical judgment. Case presentations demonstrate the principles involved in comprehensive surgical management of mandibular fractures. The techniques advocated produce anatomic reduction and restoration of physiologic function and aesthetics, with rare complications. PMID- 1585205 TI - Alternative cancer treatments: impact of unorthodox therapy on the patient with cancer. AB - So-called unorthodox methods of cancer treatment are readily available to patients and families. They are frequently claimed to be "harmless" or "nontoxic" or "painless" alternatives to more standard treatment regimens. The Congress of the United States has estimated that $2 billion is spent annually on cancer quackery. Many physicians will be asked by their patients for opinions on such alternative treatment regimens, and the purpose of this review is to provide the practitioner with the basic information necessary to discuss these topics with their patients. PMID- 1585206 TI - Erythromycin therapy for gastroparesis. AB - Gastroparesis from numerous causes has been treated with a number of prokinetic agents. We report the successful use of erythromycin as a prokinetic agent in the treatment of two cases of idiopathic gastroparesis in which treatment with metoclopramide or domperidone or both had failed. We also review information about erythromycin's mechanism of action, previous therapeutic uses, administration (doses, duration, and route), and role as an alternative to other prokinetic agents. When treatment with other agents is unsuccessful, erythromycin is a viable alternative therapy for gastroparesis. PMID- 1585207 TI - Humanism and values in the medical short stories of Arthur Conan Doyle. AB - In 1894 Arthur Conan Doyle published 15 medical short stories under the title of Round the Red Lamp, a red lamp being the symbol for a physician's office in Victorian England. These 19th-century vignettes do not indulge in scientific descriptions of diseases, their processes, or their treatment. Instead, they are based upon the effects of illness on the lives, sentiments, and emotions of the afflicted, their families, and their physicians. The stories are suffused with romance and humor. Conan Doyle's medical fiction of almost 100 years ago constitutes a superbly written and engaging collection that ranges from the comic to the pathetic. They contain universal themes that are especially appropriate today when humanistic elements are being usurped by rampant technology in both medical education and medical practice. These tales can make a significant contribution in related seminars for both students and practitioners. PMID- 1585208 TI - Some musings on the passage of words. PMID- 1585209 TI - Sirenomelia accompanying exposure of the embryo to cocaine. AB - We have reported two cases of sirenomelia sequence associated with a history of cocaine exposure during a major part or the entire extent of the first trimester of pregnancy. The two infants were delivered during a 2 1/2-year interval in a newborn population in which prenatal cocaine exposure rose to an estimated 25%. The incidence of sirenomelia in this population was 18-fold higher than previously reported. The potential relationship between sirenomelia and cocaine exposure during the first month of pregnancy warrants further investigation. PMID- 1585210 TI - Courvoisier's sign revisited: two patients with palpable gallbladder. AB - More than a century ago, Courvoisier published his observation on the significance of a palpable gallbladder in the differential diagnosis of obstructive jaundice. We have described two patients with newly described conditions--AIDS-associated cholangiopathy and diet-induced cholecystitis--who had a palpable gallbladder and have discussed possible pathogenetic mechanisms. PMID- 1585211 TI - Listerial brain abscess in long-standing sarcoidosis. AB - A 50-year-old black man with steroid-dependent stage IV sarcoidosis and a prior seizure attributed to neurosarcoidosis had progressive disorientation, ataxia, cranial neuropathies, and increased dyspnea. Neuroradiologic evaluation showed a ring-enhancing lesion in the left basal ganglion causing a mass effect. Craniotomy yielded purulent material that grew a pure culture of Listeria monocytogenes. He responded well to antibiotic therapy. PMID- 1585212 TI - Correction of HIV-associated thrombocytopenia with low doses of interferon alfa. AB - We have presented a case of HIV-associated thrombocytopenia successfully treated with low dose interferon alfa-2a. Increases in platelet levels were achieved within 1 week without hospitalization or surgery. Further, the patient had no systemic side effects from therapy. Zidovudine alone was ineffective in maintaining noncritical platelet counts. Interferon alfa-2a is a nonimmunosuppressive, nonsurgical therapy that can correct HIV-associated thrombocytopenia without requiring hospitalization. PMID- 1585213 TI - Subungual epithelioid leiomyosarcoma. PMID- 1585214 TI - The treatment of sleep disorders. AB - Narcolepsy is clinically associated with cataplexy, sleep paralysis and hypnagogic hallucinations. It is treated by reassurance (that there is no physical disease) and by stimulants such as ephedrine and amphetamine on an intermittent basis. The special tricyclic antidepressant clomipramine is also used, and mono-amine oxidase inhibitors (MAOIs) are useful in theory. Obstructive sleep apnoea is an important and often unrecognised cause of daytime somnolence. It is treated by weight reduction (pickwickian syndrome), hormones, or recently, with continuous positive pressure apparatus. Night terrors (pavor nocturnus) and sleepwalking typically occur during deep sleep (stage 3 and 4 throughout the episode) in children. In a night terror the child sits up with a scream, with eyes open, but inaccessible. He eventually falls asleep calmly. Sleepwalking, too, shows the features of inaccessibility and subsequent amnesia for the episode. Both conditions are normally treated with reassurance (to the parents) but may occasionally warrant benzodiazepines. Enuresis usually occurs in non rapid eye movement (NREM) sleep, especially stages 3 and 4. The reason for the efficacy of tricyclic antidepressants is not precisely known. Delirium tremens (DT) is treated as a rebound excess of REM sleep, with benzodiazepines and other drugs. It is the withdrawal syndrome (with or without major seizures) to the barbiturate-alcohol group of drugs, which includes alcohol, chloral, paraldehyde, glutethimide, methylprylone, ethchlorvynol, meprobamate and meprobamate diphenhydramine. Insomnia may be treated by the above drugs, by analgesics, antidepressants, major tranquillisers (neuroleptics) and miscellaneous other compounds. For the majority of patients, however, the most suitable group seems to be the benzodiazepines. The benzodiazepines are much safer than their predecessors, in both acute and chronic usage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585215 TI - Informed consent in Africa. PMID- 1585216 TI - Witness for the prosecution. PMID- 1585218 TI - Service conditions for full-time hospital doctors in rural Natal/KwaZulu. PMID- 1585217 TI - Diabetes mellitus in preschool children--an orphan disease? PMID- 1585219 TI - The clinical significance of Haemophilus influenzae and H. parainfluenzae isolated from the sputum of adult patients at an urban general hospital. AB - Fifty-seven patients, from whose sputum Haemophilus influenzae (49 cases) or Haemophilus parainfluenzae (8 cases) was isolated during a 7-month period, were studied. In the majority of cases there were well-defined predisposing factors to respiratory tract colonisation or infection with the isolates, in particular bronchiectasis and chronic obstructive airways disease. Colonisation of the airways, bronchopneumonia in patients with underlying lung disease, acute lobar pneumonia, and postoperative chest infections were the commonest clinical diagnoses. Primary acute lobar pneumonia with these organisms alone was uncommon. All of the H. influenzae isolates were nontypeable, and there was a wide range of biotypes of both organisms. Three H. influenzae isolates produced beta-lactamase, and there was, in general, a low incidence of resistance to a wide range of antimicrobial agents on disc susceptibility testing. PMID- 1585220 TI - Splenectomy in the chronic myeloproliferative syndromes. A retrospective risk versus-benefit analysis. AB - The effect of splenectomy on the course of the chronic myeloproliferative syndromes was retrospectively analysed and compared in 96 patients who underwent this procedure and 195 who did not. The operation had a 4% mortality and a 47% morbidity rate, mainly attributable to haemorrhage, infection and respiratory complications. While splenectomy conferred benefit in certain selected cases with hypersplenism, there was no significant overall improvement in the postoperative haematological values and no influence on the rate of blastic transformation. Splenectomy did not improve survival in the group as a whole, or in any subset (P greater than 0.5). In the non-splenectomy group, only a minority of patients experienced massive progressive splenomegaly and in most individuals the spleen size varied little from the time of presentation to death. Splenectomy in patients with the chronic myeloproliferative syndrome carries a significant mortality and has a high morbidity, does not reduce the rate of blastic transformation and has no influence on survival. The majority of patients on conventional therapy do not experience the discomfort of massive splenomegaly during the course of their disease and the routine use of this operation is inappropriate. PMID- 1585221 TI - Maximal work capacity and dietary status of rural black South African schoolboys aged 10-14 years. AB - The anthropometric and physical characteristics, nutritional status, exercise habits and physiological response to maximal exercise of 22 rural black schoolboys aged 9.5 to 14.5 years, attending a local farm school on the outskirts of Johannesburg, were studied. Kilojoule intake ranged from 37% to 41% of the recommended daily allowance and percentage body fat was correspondingly low. Protein intake was, however, satisfactory and there was no evidence of stunted or wasted growth. Maximum oxygen consumption (VO2 max) ranged from 48.9 ml/kg/min to 50.6 ml/kg/min and 1.55 l/min to 2.01 l/min. Despite partially inadequate nutritional intakes and regular exposure to pollutants, the maximal work capacity of these subjects compares favourably with the age-related ranges of VO2 max reported by previous researchers. A possible adaptation to nutritional and environmental stress is suggested. PMID- 1585222 TI - The role of obstetric factors in determining fetal viability. AB - OBJECTIVE: To study the influence of primary obstetric complications on the survival and short-term morbidity rates of very-low-birth-weight (VLBW) babies. DESIGN: A 1-year retrospective, descriptive study. SETTING: Department of Obstetrics and Gynaecology, Tygerberg Hospital, CP. STUDY POPULATION: 257 women admitted with live singleton fetuses and who eventually delivered babies with birth weights ranging from 750 to 1,499 g. MANAGEMENT: Primary obstetric complications responsible for the delivery of the VLBW babies were clinically diagnosed. Active management was undertaken if the fetus was viable and obstetric and neonatal resuscitation were applied. Management was conservative when the fetus was considered non-viable. This decision on the initial treatment option was taken by the obstetrician who managed the case. MAIN OUTCOME MEASUREMENTS: Survival and short-term morbidity rates of the babies. RESULTS: Spontaneous preterm labour (45%) and hypertensive disorders (39%) were equally responsible for delivery of VLBW babies at Tygerberg Hospital. The only obstetric factor influencing the babies' outcome, however, was the initial management decision by the obstetrician. There was a survival rate of 160/213 (75.1%) in the actively managed group compared with only 1/44 (2.3%) in the conservatively managed group. Other factors that significantly influenced neonatal survival of VLBW babies were: birth weight, gestational age, Apgar score at 5 minutes and length of time between admission to hospital and the delivery. CONCLUSION: The obstetric complication responsible for delivery of the VLBW baby did not influence the survival rate. The major determinant of neonatal survival was the obstetrician's decision to manage the fetus either actively or conservatively. It seems that the outcome of VLBW babies is influenced primarily by the intrinsic characteristics of the neonates' gestational age, birth weight and condition at birth, and not the reason for delivery. PMID- 1585223 TI - Health risks among white South African goldminers--dust, smoking and chronic obstructive pulmonary disease. AB - The South African goldmining industry employs a large labour force exposed to several health hazards, of which one of the most important is underground dust, containing a high level of free crystalline silica (30%). Inhalation of silica dust can cause chronic obstructive pulmonary disease (COPD). The present paper reviews the epidemiological evidence on COPD in white South African goldminers. COPD emerges as a major cause of disability and increased mortality. The associated risk factors are smoking and combined exposure to dust and smoking. In conclusion, decreased tobacco consumption in white goldminers would in most cases prevent serious lung function impairment and the premature deaths associated with it. PMID- 1585224 TI - Effect of maternal nicotine exposure on neonatal lung elastic tissue and possible consequences. AB - The effect of maternal nicotine exposure (1 mg/kg body mass/d) on the lung elastic tissue of 1-day-old rat pups was investigated. The results show that maternal nicotine exposure resulted in a very low elastic tissue content in the lungs of these rat pups compared with those of the controls. This may interfere with normal lung development since elastic tissue is part of the lung connective tissue structure and is involved in the formation of alveoli. Impaired elastic synthesis may thus make the rat pups more susceptible to lung diseases such as emphysema. PMID- 1585225 TI - The doctor as witness in child abuse cases. AB - Doctors who have to give evidence in cases of physical or sexual child abuse usually find it a stressful experience. Factors that may help to improve the doctor's ability to cope with the situation are discussed in this article. The importance of good medical notes and a good medical examination is stressed. Hints are given on how to minimise the inevitable delays that precede a court appearance. The hearsay rule means that the history the doctor obtains is not accepted as evidence. The medical procedure, which involves using various facts to build up a complete picture, is contrasted with the legal procedure, which involves testing each separate fact in order to create reasonable doubt that the accused may be guilty. Some common questions put to the doctor are discussed here. They include questions as to whether causes other than abuse, such as masturbation, infection or the use of other instruments, could have damaged the hymen or vagina. PMID- 1585226 TI - Continuous intravenous propofol with nitrous oxide for ocular surgery. A comparison with etomidate, alfentanil, nitrous oxide and isoflurane. AB - Propofol, administered intravenously for induction and as a continuous maintenance anaesthetic with nitrous oxide, was compared, in a group of elderly patients scheduled for ophthalmic surgery, with an anaesthetic technique (etomidate, alfentanil, nitrous oxide and isoflurane) specifically chosen to be haemodynamically stable and evanescent in action. Both techniques resulted in similar effects on blood pressure after induction, intubation and surgical incision, but propofol did not prevent increases in heart rate as effectively at these times. Furthermore, during maintenance anaesthesia, cardiovascular stability and anaesthetic depth were more easily achieved in the group where etomidate, alfentanil and isoflurane were used. Propofol decreased intra-ocular pressure after intubation, while in both groups recovery was rapid with no significant complications. A subgroup of patients receiving alpha-methyldopa had significantly longer post-anaesthetic recovery times. PMID- 1585227 TI - Adult T-cell leukaemia/lymphoma associated with HTLV-I in Natal. PMID- 1585228 TI - Quality control of red blood cell cholinesterase estimations. PMID- 1585229 TI - Ovarian cancer masquerading as ectopic pregnancy. PMID- 1585230 TI - A stroke of luck. PMID- 1585231 TI - [Chronic myeloid leukemia beginning as thrombocythemia. Analysis of 5 cases]. AB - The clinico-haematological and evolutive features of five patients with Ph' positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients. PMID- 1585232 TI - [Hodgkin's disease. Our 9-year experience with the 1980 protocol]. AB - The purpose of this work was to evaluate the therapeutic results attained with our 1980 protocol for Hodgkin's disease. The usefulness of staging laparotomy was also analysed. Along a 9-year period, 94 patients were diagnosed (stages IA and IIA: 26 cases, IB, IIB and IIIA: 24 cases, and IIIB and IV: 44 cases). The complete remission (CR) rate, as a whole, was 85%; there were 14 relapses, of whom a new CR was attained in 9 instances. The overall actuarial survival is 64% at 47 months. The appearance of 3 cases of acute non-lymphoblastic leukaemia is noteworthy. Laparotomy induced changes of the patient's staging in 49% of cases (rise in 43% and descent in 6%). In account of this, laparotomy seems an adequate procedure in staging, although the criteria for selecting the patients who will undergo this, procedure should be perhaps restrictive. PMID- 1585233 TI - [Essential thrombocythemia: a myeloproliferative state on the rise. Clinico biological study and course of 44 cases]. AB - Forty-four cases of essential thrombocytosis (ET) were diagnosed in the last 20 years, 19 males and 24 females (M/F: 0.76), aged between 3 and 86 years (median, 62 years), and 9 of them being under 40 years of age. The M/F ratio for patients under 60 years was 0.5, whereas it was 1.09 for patients over 60. The clinical forms at onset were: asymptomatic, 36.5%; as a bleeding disorder (BD), 20.4%; as thrombotic disease (TD) 22.7%; BD/TD, 13.6%, and others, 6.8%. The most important biological features included platelet count over 1.000 x 10(9)/L (59.1%), abnormal platelet aggregation, chiefly with ADR (56.5), mild reticulin myelofibrosis (55%), abnormal karyotype (2.6%), moderately high LDH levels (56.8%) and pseudo-hyperkalaemia (40%). The initial therapeutic approach was: observation (12 cases), antiaggregating agents (6 cases), and chemotherapy (BSF, HU, etc.) in the remainders. One patient evolved quickly into acute myelogenous leukaemia and two others suffered a late transformation into polycythaemia vera (PV) and myeloid metaplasia, respectively. The median survival was over 11 years, this being longer in patients under 60 years of age, in those with platelet count at diagnosis between 600 and 1000 x 10(9)/L and in those without initial symptoms of thrombosis. The advent of electronic blood-cell counters has made ET no longer a rare chronic myeloproliferative disease, its incidence coming now closer to that of PV; thus, in the last four quinquennial periods the incidence of ET/PV has evolved as following: 1/19, 4/16, 13/18 and 26/29. PMID- 1585234 TI - [Hyperleukocytic acute leukemia. Clinico-biological characterization, response to treatment and prognostic factors]. AB - The white-cell count acquires an important prognostic value in acute leukaemia. Thus, very high leucocytosis conveys high risk of early death due to leucostasis. The clinico-biological features at diagnosis, response to therapy and prognostic factors of 69 cases of acute leukaemia with hyperleucocytosis (ALHL) are reported in this paper. All the patients had white-cell count over 100 x 10(9)/L and had been followed up at the Haematology Service of the Hospital La Fe between 1977 and 1989. There were 49 cases of acute nonlymphoblastic leukaemia (ANLL), 18 cases of acute lymphoblastic leukaemia (ALL) and 2 of unclassified acute leukaemia. The incidence of ALHL was 14%, and the mortality on the first week after diagnosis reached 20%, this being higher in ANLL. The actuarial median of complete remission duration was 9 months. The achievement of remission was associated with the morphological subtype, the patient's age and the presence of constitutional symptoms at onset, while the duration of remission was associated with the presence of fever and the need more than one chemotherapy course to attain remission. ALHL need new therapeutic strategies in order to diminish the rate of early death and to achieve longer survival. PMID- 1585235 TI - [Nitrates as antiplatelet agents]. PMID- 1585236 TI - [Intracranial hemorrhage in hemophiliacs. Study of 10 episodes]. AB - The intracranial haemorrhages presented within a group of 64 haemophiliacs along 25 years were revised. During this period, 10 such episodes were seen in 8 patients with haemophilia A; six of them appeared in children under 10 years of age. In five instances there were traumatic antecedents, whereas in the remaining five the haemorrhage was spontaneous, no vascular abnormalities being demonstrated in these last. The lesions observed were: intracerebral haematoma in three instances, subdural haematoma in four, subarachnoid haemorrhage in two cases and cerebellar haematoma in one case. Only one of the episodes was lethal, death being related with infectious complications. Recurrences were observed in two patients. Two patients had sequelae with seizures, plus mental retardation and motor deficit in one of them. Substitutive therapy shows capable of controlling this severe complication of haemophilia, provided it is started promptly and fair rates of factor VIII are maintained. Such therapy must be kept for longer periods in these patients with traumatic antecedents. PMID- 1585237 TI - [Description of 2 patients with cytogenetically abnormal clones]. AB - We present two patients with two cytogenetically unrelated clones. A patient was diagnosed of refractory anaemia and showed an abnormal clone with trisomy 8 and other clone with 5q-; the other patient, diagnosed as chronic lymphocytic leukaemia showed a clone with an inversion of chromosome 2, inv(2) (p23q12) and the other clone with a 47,XX,+5,t(16;17)(p13;q11),+2ac karyotype. The discussion is focused on the presence of unrelated clones in relation to the monoclonal origin of cancer. PMID- 1585238 TI - [Effect of heparin and/or antithrombin III in a model of disseminated intravascular coagulation induced by endotoxin in rabbits]. AB - Disseminated intravascular coagulation (DIC) was induced in 84 rabbits by intravenous infusion of 20 micrograms/kg/h of endotoxin during 6 hours. The following treatments were administered simultaneously with endotoxin: heparin, 5, 10 and 20 UI/kg/h, antithrombin III (AT III), 10, 20 and 40 U/kg/h or as a 240 U/kg bolus dose, and heparin (10 UI/kg/h) plus AT III (20 U/kg/h). Blood samples were taken before endotoxin and 2 and 6 hours after endotoxin to perform screening coagulation assays, factors V, VIII and XII, AT III, fibrin monomers and fibrinogen degradation products. All treatments were able to modify some of the parameters related to DIC, but only AT III bolus dose and heparin plus AT III significantly reduced fibrin deposition in kidneys (p less than 0.05). All the therapeutic schedules significantly diminished the mortality rate. We conclude that AT III bolus dose and heparin plus AT III are useful in the treatment of endotoxin-induced intravascular coagulation in rabbits. PMID- 1585239 TI - [Multiple renal masses as a complication in a patient with Hodgkin's disease in remission. Recurrence or primary tumor?]. AB - A forty-eight year old man with Hodgkin's disease in complete remission after 8 cycles of polychemotherapy (COPP) is presented. In an abdominal tomography, practiced 18 months after completion of treatment, two masses were found on the left kidney. Differential diagnosis between a Hodgkin's recidive and a second primary tumor and the implication of Hodgkin's treatment in the appearance of other neoplasms are discussed. Literature is reviewed. PMID- 1585240 TI - [Acute monoarthritis and laryngeal obstruction as extralymphatic manifestations of non-Hodgkin's lymphoma]. AB - Joints and larynx are uncommonly involved by non-Hodgkin's lymphoma (NHL). Synovial involvement has been reported in only 7 cases, mainly located in the knees. When this is the first location of NHL it is usually misdiagnosed. The treatment of choice is local radiotherapy followed by systemic chemotherapy. Laryngeal lymphoma can be either primary or forming part of multifocal disease. The prognosis of the primary form is usually good only with radiotherapy, whereas the prognosis of the laryngeal location of advanced disease is rather poor. The symptoms include dysphonia and slowly progressive dyspnea. A case of NHL is presented who showed initial arthritis of the knee, later evolving into severe laryngeal obstruction, an association not previously reported. PMID- 1585241 TI - Sea-blue histiocytosis in a family with Niemann-Pick disease. A clinical, morphological and biochemical study. AB - Four siblings of a large Brazilian kindred are shown to have a variant of Niemann Pick disease masquerading as the sea-blue histiocyte syndrome. They show a very similar clinical and laboratory picture: massive hepatosplenomegaly, low height for age, diffuse interstitial pulmonary infiltration, high levels of serum acid phosphatase and sea-blue histiocytes in the bone marrow. The neurological examination, as well as the retinae and maculae are normal. The high-density lipoprotein serum cholesterolemia ranged from 8.6 to 13.9 mg/dl, much lower than the 5th centile of normal distribution. The AI apolipoprotein concentrations in two siblings (0.29 and 0.44 g/l) were also below the minimal reference level of 0.90 g/l. The histochemical reactions demonstrated that sphingomyelin and ceroid are the accumulating substances in the marrow histiocytes. Electron microscopically, the cytoplasmatic granules of the histiocytes are phagolysosomes which contain scarce amorphous material, loose arranged lamellae, or dense well organized structures with a fingerprint or fine network pattern. The sphingomyelinase activity in leucocyte extracts ranged from 4.9 to 8.6% and in cultured fibroblast extracts from 7.7 to 10% of simultaneous controls. The activity of other lysosomal enzymes was normal. Accordingly, this variant of Niemann-Pick disease should be classified as chronic nonneuronopathic sphingomyelinase-deficient type. The present data suggest that this variant is inherited as an autosomal recessive character. Our findings support the view that the sea-blue histiocyte syndrome is not an independent entity. PMID- 1585242 TI - [History of hematology/hemotherapy in Aragon]. PMID- 1585243 TI - [Phenotypic changes in a case of T-ALL]. PMID- 1585244 TI - [Marrow necrosis as the initial manifestation of a blast crisis in CML]. PMID- 1585245 TI - [Toxic neuropathy of the trigeminal after administration of vincristine. A rare complication]. PMID- 1585246 TI - [Utility of the Sysmex NE8000 counter in the diagnosis of hemoglobin C]. PMID- 1585247 TI - [Levels of 2,3-DPG in a group of long-distance runners]. PMID- 1585248 TI - [Possibilities of nuclear magnetic resonance tomography in diagnosis of osteochondrosis dissecans of the knee joint]. AB - 20 patients who suffered from osteochondrosis dissecans in the knee were examined by x-ray and MRI. Afterwards all joints were evaluated by arthroscopy. On plain x ray the judgement of joint cartilage is not possible. With the use of MRI, the hyaline cartilage can be documented. Even without any visible changes on x-ray, MRI clearly reveals pathologic bone patterns. Comparing areas of sclerosis on x ray with MRI changes, the real diameter of osteochondrosis dissecans can only be seen on MRI. PMID- 1585249 TI - [Injuries of the cruciate ligament in children caused by sports accidents]. AB - From 1982 to 1990, 87 knee arthroscopies were performed on children aged 13 years and younger, following post-traumatic haemarthrosis. Damage to anterior and posterior cruciate ligaments was found in more than 1/3 of these cases. The injury to the actual anterior cruciate ligament occurred more often than the injury associated with avulsion fracture of the tibial eminences. It was found that almost all of the ruptures to the actual anterior and posterior cruciate ligaments occurred proximally. Hence, if haemarthrosis occurs in children, arthroscopy should be performed as a diagnostic and therapeutic measure. Surgery must follow the complete rupture of the actual ligaments and dislocated fracture of the bony insertions. The outcome of these operations on children is very satisfactory. PMID- 1585250 TI - [Nuclear magnetic resonance tomography and sonography in diagnosis of lesions of the rotator cuff]. AB - The diagnostic value of MRI and ultrasound in the examination of 37 patients with chronic shoulder pain is compared. All the results were controlled or by arthroscopy/arthrotomy or by arthrography. Ruptures and degenerative changes of the rotator cuff and degenerative lesions could be detected with a high sensibility. The ultrasound examination as a fast, reproducible diagnostic method has now become part of the routine diagnosis. The MRI produces exacter information about the extent of the lesions; but it will be reserved for special questions. PMID- 1585251 TI - [An interesting case. Blunt thoracic trauma]. PMID- 1585252 TI - [Isolated injury of the subscapular muscle tendon]. AB - Avulsion of the subscapularis tendon is caused by a combined abduction and external rotation trauma of the upper limb. Weakness of internal rotation and a positive apprehension test are clinical signs of the injury. A fracture of the lesser tuberosity in the x-ray film or a disruption of the subscapularis tendon documented in dynamic sonography of the shoulder clarify the diagnosis. Operative treatment is indicated of prevent weakness of internal rotation as well as anterior instability. This recommendation is supported by four cases with full range of motion and good anterior stability after surgery. PMID- 1585253 TI - [Insertion tendinopathy of the knee joint in bicycle athletes in relation to body position and shoe-pedal position]. AB - If a Biker complains about pain in the knee joint, one should consider the possibility of overstrain. Causes would be a wrong sitting position and a non fitting connection between shoe and pedal. Even a minimal change of this parameters can avoid a frustrating longtime treatment. PMID- 1585254 TI - [Analysis of isokinetic and isometric muscle function after arthroscopic anterior cruciate ligament repair]. AB - Following anterior cruciate ligament replacement plasty performed via arthroscopy, isokinetic and isometric power data were measured at the beginning and end of a sports therapy treatment course. Evaluation yielded surprising results that were partly contradictory to those communicated in current literature. Besides the dependence of force values on preset velocities of motion in dynamic measurements (isokinetics) or in static measurements (isometrics), markedly lower losses of power than expected were measured in the involved extremity on repeated power application. Possible reasons are discussed on the basis of specific innervation criteria and polymodal reflexes. We assume that muscle potential is not yet fully available after surgical intervention, due to reflexive modulations of power realisation, so that the joint and especially the anterior cruciate ligament are thus protected from damage. PMID- 1585255 TI - Excitatory amino acid antagonists protect mice against MPP+ seizures. AB - Administration of 1-methyl-4-phenyl-pyridinium ion (MPP+) into the lateral ventricle of mice induced clonic convulsions and lethality in a dose- and age dependent manner. MPP+ failed to induce seizures in 4-day-old mice, and the convulsant response to MPP+ was enhanced in aged mice. The seizures triggered by MPP+ in adult mice were blocked by coadministration of L-glutamate antagonists active at kainate/AMPA receptors such as gamma-D-glutamylaminomethylsulphonate and 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo[f]quinoxaline. The N-methyl-D aspartate (NMDA) antagonist 2-amino-7-phosphonoheptanoate, but not kynurenate, also protected mice against MPP+ convulsions. Similarly, the benzodiazepine midazolam and the adenosine A1 agonist 2-chloroadenosine, but not antiepileptic drugs such as phenobarbital, trimethadione, ethosuximide, or acetazolamide, showed a protective efficacy against seizures. Additionally, the excitatory amino acid antagonists as well as phenobarbital, midazolam and 2-chloroadenosine protected mice against MPP+ lethality. These data suggest that convulsant action of MPP+ and its lethality in rodents may be mediated by excitatory amino acids. PMID- 1585256 TI - Quantitative autoradiography of cocaine binding sites in human brain postmortem. AB - Quantitative autoradiography was used to study cocaine binding sites in the human brain postmortem. Tritiated cocaine was applied to brain sections from three drug and disease-free subjects at a low (10 nM) concentration and at a high (1 microM) concentration, the latter being in the range of brain concentrations of cocaine found in users of the drug. Nonspecific binding was assessed in the presence of 100 microM unlabeled cocaine. At low (10 nM) concentrations of labeled cocaine, the basal ganglia exhibit the highest density of binding sites, with considerably lower densities in thalamus, cortex, and hippocampus. Cocaine binding at high (1 microM) concentrations displayed a different distribution pattern, more homogeneous with some cortical regions exhibiting binding site densities close to those seen in the basal ganglia. Preliminary competition experiments with several drugs indicate that dopamine uptake inhibitors completely block cocaine binding to the basal ganglia, while serotonin uptake inhibitors were more effective in the hippocampus. These findings suggest that cocaine binds to dopamine uptake sites in the human basal ganglia postmortem but that it also interacts with other classes of binding sites, depending on the concentration and brain region examined. PMID- 1585257 TI - Clinical and biochemical aspects of depressive disorders: III. Treatment and controversies. AB - The present document is the final of three parts of a review that focuses on recent data from clinical and animal research concerning the biochemical bases of depressive disorders, diagnosis, and treatment. Various treatments for depression, including psychotherapy, pharmacological, and somatic treatments, will be described in this third part. Also, some of the controversies in the field, as well as a summary of the most salient points of the review, will be discussed. Previous sections of this review dealt with the classification of depressive disorders and research techniques for studying the biochemical mechanisms of these disorders (Part I) and various transmitter/receptor theories of depressive disorder (Part II). PMID- 1585258 TI - In vivo imaging of dopamine reuptake sites in the primate brain using single photon emission computed tomography (SPECT) and iodine-123 labeled RTI-55. PMID- 1585259 TI - A light and electron microscopic study of dystrophin localization at the mouse neuromuscular junction. AB - Duchenne muscular dystrophy (DMD) is characterized by a lack of dystrophin expression. Dystrophin is a 420 Kd protein localized in the muscle sarcolemma that most likely provides stability to the muscle plasma membrane. Neuromuscular junctions (NMJs) were localized by revealing either the acetylcholine receptors (AChRs) with alpha-bungarotoxin coupled with cascade blue or by revealing desmin, a protein found in higher concentration at the NMJs using immunochemistry. An accumulation of dystrophin was observed in normal mice by immunoperoxidase labelling at NMJs identified with these markers. Dystrophin was pinpointed on the postjunctional folds of NMJs by electron microscopy and was more abundant on the postjunctional membrane than on the remaining muscle membrane. Our observations are similar to previous observations suggesting that dystrophin may interact with the AChRs. PMID- 1585260 TI - Quantitative autoradiographic mapping of 5-HT3 receptors in the rat CNS using [125I]iodo-zacopride and [3H]zacopride as radioligands. AB - Substitution of the chlorine atom by a radio-iodine in position 5 in the zacopride molecule yielded [125I]iodo-zacopride that bound with high affinity (Kd = 4.3 nM) to 5-HT3 receptors in the rat central nervous system. Assays with membranes from the posterior (mainly entorhinal) cortex confirmed that the pharmacological properties and regional distribution of [125I]iodo-zacopride specific binding sites were identical with those of 5-HT3 sites labelled by the reference radioligand [3H]zacopride. Autoradiographic investigations for the visualization and quantification of 5-HT3 receptors yielded similar results with both radioligands, but autoradiograms could be obtained after only 1-3 days of exposure of sections labelled with [125I]iodo-zacopride, instead of 4-6 months using [3H]zacopride. The highest density of 5-HT3 sites was found in the nucleus tractus solitarius followed by, in decreasing order, the dorsal motor nucleus of the vagus nerve, the superficial layers of the dorsal horn in the spinal cord, the nucleus of the spinal tract of the trigeminal nerve, and the area postrema. Significant labelling of 5-HT3 receptors was also observed in limbic areas (amygdala, hippocampus, frontal and entorhinal cortex), and to a much lower extent in the dorsal raphe nucleus, striatum, and substantia nigra. These multiple locations further support the idea that 5-HT3 receptors are probably involved in several 5-HT-mediated functions in the central nervous system. PMID- 1585261 TI - Characterization of antagonistic activity and binding properties of SR 95531, a pyridazinyl-GABA derivative, in rat brain and cultured cerebellar neuronal cells. AB - Experiments were performed to characterize the antagonistic activity and binding properties of SR 95531 [2-(3' carbethoxy-2'-propyl)-3-amino-6-paramethoxy-phenyl piridazinium bromide] in rat brain. SR 95531 and bicuculline methiodide inhibited muscimol-stimulated 36Cl- uptake in cortical synaptoneurosomes in a concentration dependent manner. The inhibitory potency of SR 95531 for the muscimol-stimulated 36Cl- uptake was 15 times higher than that of bicuculline methiodide. Scatchard plots of binding isotherms exhibited two apparent binding sites for [3H]SR 95531 in both the frontal cortex and cerebellum. The IC50 value of SR 95531 for muscimol-stimulated 36Cl- uptake into cortical synaptoneurosomes was in close agreement with the KD value of low-affinity binding sites of [3H]SR 95531 in the frontal cortex. Pretreatment of the membranes with phospholipase A2 invariably decreased [3H]SR 95531 binding in the frontal cortex and cerebellum. On the other hand, the treatment significantly increased [3H]gamma-aminobutyric acid (GABA) binding in a concentration-dependent manner in the frontal cortex. Although lower concentrations of phospholipase A2 did not affect [3H]GABA binding in the cerebellum, treatment with higher concentrations of phospholipase A2 increased the binding in this region. Specific binding of [3H]SR 95531 was also detected in cultures rich in cerebellar granule cells. Pretreatment with phospholipase A2 affected the binding of [3H]GABA and [3H]SR 95531 in these cells, as in the case of the cerebellum. These effects of phospholipase A2 on the binding of [3H]GABA and [3H]SR 95531 were partially prevented by the addition of delipidated bovine serum albumin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585262 TI - 5-Hydroxytryptamine increases excitability of CA1 hippocampal pyramidal cells. AB - In the presence of spiperone to block the 5-HT1A-mediated inhibition of pyramidal cell activity, 5-hydroxytryptamine (serotonin, 5-HT) produces a rapid transient increase in amplitude of the extracellularly recorded population spike from area CA1 of the hippocampus. Intracellular recording techniques in area CA1 of rat hippocampal slices were used to identify the ionic mechanism and to characterize the 5-HT receptor mediating this excitatory response to 5-HT. Most of the experiments were conducted in the presence of spiperone to block the 5HT1A hyperpolarization. Since spiperone also has high affinity for 5-HT2 receptors, any response mediated by 5-HT2 receptors would also be blocked. Bath perfusion of the slice with 5-HT increased the rectification of pyramidal cells in the subthreshold region, increased the resistance, and increased the amplitude of subthreshold excitatory postsynaptic potentials (EPSPs) to initiate spike firing. The 5-HT2,1C-selective agonist DOI mimicked this effect of 5-HT, and the 5-HT2,1C antagonist ketanserin (1 microM) blocked the effect of DOI. There was no change in the amplitude of the slow afterhyperpolarization (sAHP) or the amplitude of evoked inhibitory postsynaptic potentials (IPSPs). The increase in rectification and EPSP amplitude by 5-HT occurred even in the presence of the 5-HT4-selective antagonist BRL 24924 to prevent the decrease in amplitude of the sAHP by 5-HT. We conclude that 5-HT produces a fast excitatory response by increasing subthreshold conductance in CA1 hippocampal pyramidal cells. The identity of the receptor mediating this response was not conclusively identified, but resembled the 5-HT1C receptor. PMID- 1585263 TI - Direct muscarinic and nicotinic receptor-mediated excitation of rat medial vestibular nucleus neurons in vitro. AB - We have utilized intracellular recording techniques to investigate the cholinoceptivity of rat medial vestibular nucleus (MVN) neurons in a submerged brain slice preparation. Exogenous application of the mixed cholinergic agonists, acetylcholine (ACh) or carbachol (CCh), produced predominantly membrane depolarization, induction of action potential firing, and decreased input resistance. Application of the selective muscarinic receptor agonist muscarine (MUSC), or the selective nicotinic receptor agonists nicotine (NIC) or 1,1 dimethyl-4-phenylpiperazinium (DMPP) also produced membrane depolarizations. The MUSC-induced depolarization was accompanied by decreased conductance, while an increase in conductance appeared to underlie the NIC- and DMPP-induced depolarizations. The muscarinic and nicotinic receptor mediated depolarizations persisted in tetrodotoxin and/or low Ca2+/high Mg2+ containing media, suggesting direct postsynaptic receptor activation. The MUSC-induced depolarization could be reversibly blocked by the selective muscarinic-receptor antagonist, atropine, while the DMPP-induced depolarization could be reversibly suppressed by the selective ganglionic nicotinic-receptor antagonist, mecamylamine. Some neurons exhibited a transient membrane hyperpolarization during the depolarizing response to CCh or MUSC application. This transient inhibition could be reversibly blocked by the gamma-aminobutyric acid (GABA) antagonist, bicuculline, suggesting that the underlying hyperpolarization results indirectly from the endogenous release of GABA acting at GABA receptors. This study confirms the cholinoceptivity of MVN neurons and establishes that individual MVN cells possess muscarinic as well as nicotinic receptors. The data provide support for a prominent role of cholinergic mechanisms in the direct and indirect regulation of the excitability of MVN neurons. PMID- 1585264 TI - Use of 6,000 IU vitamin A during early pregnancy without teratogenic effect. PMID- 1585265 TI - From the pages of Teratology--vitamin A to pseudoephedrine issues in patient counseling. PMID- 1585267 TI - Morphometric analysis of heterozygote dancer mice predisposed to 6 aminonicotinamide-induced cleft lip. AB - Mid-facial development is an extremely complex process involving coordinated events and precise timing. Cleft lip (CL) may result from the failed fusion of the lateral and medial nasal processes in the developing embryo. It has been postulated that spontaneous CL in the A/J strain of mice may be due to a predisposing face shape (Trasler, '68). This hypothesis was examined in mutant mice susceptible to teratogen-induced CL. Mice carrying the dancer (Dc) mutation in the heterozygous state rarely develop CL, whereas 90% of homozygotes (Dc/Dc) develop CL. Outcrossed heterozygotes show elevated susceptibility to 6 aminonicotinamide (6AN)-induced CL (Trasler et al., '84) and these were used to investigate face shape as a predisposing factor. Dc/+ and +/+ males were mated to R stock females, and embryos were collected on day 10/21 hr, when the nasal placodes are approximately at the oblong or crescent stage. Total nasal process areas and volumes, medial and lateral process areas and volumes, and medial jut lengths were measured from histological sections, and comparisons made between the two populations. The results indicate that compared to +/+ control, heads of embryos from the Dc/+ cross have significantly smaller mean total process areas and volumes (P less than 0.005), mean lateral process areas and volumes (P less than 0.005), mean medial process area and volumes (P less than 0.01), mean maximum head diameter (P less than 0.02), but similarly sized medial juts and crown rump lengths. Correlations between maximum head diameter and process size indicate that the Dc mutation may hinder normal development of the nasal processes. These reduced nasal processes may explain the underlying predisposition to 6AN-induced CL. PMID- 1585266 TI - Embryonic palatal responses to teratogens in serum-free organ culture. AB - This study examines development of rat, mouse, and human embryonic palates in submerged, serum-free organ culture. The concentration-response profiles for retinoic acid (RA), triamcinolone (TRI), hydrocortisone (HC), dexamethasone (DEX), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were examined and the mechanisms of clefting in vitro were compared to observed in vivo responses. Craniofacial regions were dissected on gestational day (GD) 12 for mice and GD 14 for rat, and cultured for 3-4 days in Bigger's BGJb medium in flasks flushed with 50% O2, 45% N2, 5% CO2. Growth and fusion of secondary palates were scored under a dissecting microscope. In serum-free control medium, mouse and rat palatal fusion occurred within the 4-day culture period. Supplementing with fetal bovine serum (FBS) in excess of 1% interfered with growth and fusion in control medium. RA significantly inhibited fusion of mouse and rat palates at 5 x 10(-9) and 1 x 10(-10) M, respectively, with RA-induced clefting related to abnormal proliferation and differentiation of medial epithelia. In contrast, glucocorticoid-induced clefting was due to concentration-dependent inhibition of shelf growth. TRI significantly inhibited fusion at 4 x 10(-5) M, and 1 x 10(-4) M DEX or HC, inhibited fusion of 19 and 42% of shelves, respectively. The response rate for DEX in the presence of 1% FBS was increased (42% unfused). TCDD clefting was due to altered medial epithelial differentiation and 1 x 10(-8) M TCDD affected 36% of CD-1 mouse, 23% of C57BL/6N mouse, and 47% of F344 rat palates. When the medium was supplemented with 1% FBS, selenium, transferrin, and additional glutamine, the response of C57BL/6N embryos increased to 75%. This rate is similar to that reported for Trowell's-type cultures with IMEM:F12 medium and 1% FBS. The increased responsiveness to DEX or TCDD in the presence of serum suggests that an unknown factor in serum may be required for full activity. Three human embryonic palatal explants (GD 52 or 53) were cultured for 3-6 days and fused during culture. The present study demonstrates that serum-free organ culture supports development of mouse, rat, and human palatal explants. The present study demonstrates the capacity of this organ culture system to model palatogenesis for several species, and to distinguish between various mechanisms of clefting as presented through selected model compounds. This model should be useful for exploring mechanisms of activity at a cellular and molecular level. PMID- 1585268 TI - [Hypophyseal dysfunction and tumors]. AB - Some pituitary hormones secrete hormones while others do not. Nonsecreting tumors can interfere with normal pituitary hormone secretion and produce tumor symptoms and signs like headaches and visual field defects. The most frequent hormone secreting tumors are prolactinomas. Growth hormone or ACTH or gonadotropin or gonadotropin-alpha and beta chain-producing tumors are less frequent, TSH producing tumors are extremely rare. The most important elements of the diagnostic work-up are clinical signs and symptoms, assessment of pituitary function (measurement of TSH, free T4, LH, FSH, oestradiol/free testosteron, growth hormone, IGF-1, prolactin, ACTH, Cortisol, serum and urine osmolality), CT and/or MRI and, in patients with large tumors, a visual field exam. The treatment of choice of pituitary tumors is often surgery. Alternative therapies are radiation treatment (in nonoperable patients or when hormone levels are persistently elevated after pituitary surgery) and drug treatment (dopamine agonists in hyperprolactinemia, somatostatin analogues in acromegaly). Pituitary hormone deficiencies are treated depending on the specific deficiency with thyroxine, cortisone, oestrogen/gestagen/testosterone gonadotropines or ADH analogues. PMID- 1585269 TI - [Adrenal gland disorders]. AB - Adrenal diseases are generally rare but of variable manifestation and high diagnostic expenditure for definitive conformation of the disease in the individual case; therefore, the definitive diagnosis is often made by the specialist. On the other hand the supposed diagnosis, based on the knowledge of clinical symptoms, is frequently made by the nonspecialist who also initiates the first diagnostic steps in order to confirm or exclude the diagnosis. It is the aim of this survey to discuss not only the clinical symptoms of the most important adrenal diseases, but also the essential diagnostic steps in order to at least narrow down the diagnosis with as little expenditure as possible and to avoid a diagnostic maze. PMID- 1585270 TI - [Struma, hyper- and hypothyroidism]. AB - Careful history and physical examination form the basis of thyroid diagnostics. They are important for the choice of the appropriate laboratory and imaging tests such as sonography and scintigraphy. Estimation of FT4 and TSH (measured with a 'sensitive' assay) are nowadays considered to be the principal laboratory tests for thyroid disease. Euthyroidism and hypothyroidism are confirmed by measuring FT4 and TSH (not FT3 or TT3), hyperthyroidism by measuring FT3, FT4 and TSH. If a goitre is observed, the primary tests are TSH and sonography. PMID- 1585271 TI - [Hyper- and hypocalcemia--diagnosis and therapy]. AB - The establishment of an abnormal calcemia first requires confirmation by a second measurement that should then be interpretated in relation to albuminemia. Should the abnormality be confirmed, measurement of intact parathormone in serum can help distinguishing between a parathyroid or nonparathyroid source of origin. In presence of a plasma calcium level lower than or equal to 2.9 mmol/l regular monitoring should be investigated and aggravating factors such as thiazide diuretics, dehydration or high calcium intake avoided. If plasma calcium is greater than 3 mmol/l the patient should first be rehydrated. In case of primary hyperparathyroidism, parathyroidectomy is the only effective treatment. In neoplastic hypercalcemia, bisphosphonates are the first-choice treatment when antitumoral therapy turns out to be insufficient. Hypocalcemia can be effectively corrected by calcium and by vitamin-D derivatives. PMID- 1585272 TI - [Osteoporosis]. AB - An exact diagnostic classification in primary or secondary osteoporosis may have therapeutic consequences. This review thus covers clinical, biochemical, radiological and bioptic diagnostic procedures. The most effective prophylactic measures, i.e. physical exercise, nutrition rich in calcium and estrogen-gestagen substitution, are spotlighted. Finally, various current therapeutic modalities are critically discussed, namely calcium supplements, the osteoclast inhibitors, calcitonin and bisphosphonates, as well as the osteoblast stimulators, anabolic steroids and fluorides. PMID- 1585273 TI - [Gynecologic endocrinology]. AB - Today, the specialty gynaecological endocrinology covers a very large field of physiological and pathophysiological mechanisms as well as endocrine diseases related to the ovarian axis. Gynaecological endocrinological processes accompany a wife from pregnancy and birth to the late postmenopause, passing through puberty, irregularities of the menstrual cycle, androgenization and infertility. The present review intends to give an overview on the different ways of investigation and of treatment typical for each endocrine problem in gynaecology and to point to some easily accessible literature. PMID- 1585274 TI - [Endocrine fertility disorders in the male]. AB - Every seventh couple in the general population is confronted in their marriage in one way or another by the phenomenon of an unfulfilled desire to have children and hence of a trouble of fertility. In half of these couples there is a fertility problem of the female, in 30% of the male and in 20% of both partners. Therefore, the husband contributes in half of the cases to infertility. The great majority of male troubles of fertility is either idiopathic, i.e. without underlying organic causes, or there is a varicocele. Endocrine causes of infertility are rare in the male subject, the frequency being below 3%. PMID- 1585275 TI - [Disorders of puberty and gonadal disorders in the child]. AB - Normal puberty has a characteristic harmony or consonance between the individual modalities of sexual maturation. Thus, the objective description and detailed knowledge of physical pubertal development is the basis of the clinical analysis of pubertal disorders. An aim of the review is to provide details of the visible changes the clinician must note in order to document the normal progression of puberty. Disorders of puberty can be classified by the timing of onset of sexual characteristics into either precocious or delayed puberty. A more useful concept, however, than the abnormalities of timing of puberty is whether the pubertal development is true (consonant) or if there is a pseudo-puberty (absence of consonance). This is of greater significance in relation to the pathophysiology and, therefore, the investigations and therapies which will be required. The use of either well known or new agents that may be used for treatment of pubertal disorders are presented. PMID- 1585276 TI - [Growth disorders]. AB - Growth assessment forms the basis of the management of endocrine disorders in childhood. However, it is important to emphasize that there is no clear demarcation between normal and abnormal stature and that an understanding of the various components of growth and its endocrine correlate is a basis of the logical investigations and the eventual diagnosis of growth disorders. In this context it is obvious that the definition of a tall or a short child is arbitrary. In fact, normal growth embodies many normal variants, not only terms of growing within or outside the percentiles, but also in terms of skeletal maturation and duration of puberty. It is worth reinterating that percentiles mean nothing more than the proportion of children who had reached given heights at given ages when they, the standardizing population, were measured. Therefore, percentile position in itself is of no consequence in the diagnosis or management of an individual child. To estimate the rate at which a child is growing, it is necessary to measure height on more than one occasion over a not too short period of time and to divide the increment in height by the time elapsed. As the growth of a normal child tends to follow a particular percentile an endocrine investigation becomes only necessary if a child is growing extremely quickly or slowly and if a significant deviation from the percentile lines becomes apparent. PMID- 1585277 TI - Comparative haemodynamic examination of Nitromint (sublingual tablet and aerosol). AB - The hemodynamics influencing effect of Nitromint sublingual tablet and aerosol (EGIS Pharmaceuticals) has been examined in 22 ischaemic heart disease patients during heart catheterisation. The patients were hospitalized and took also the earlier prescribed drugs. On the basis of the results of examinations it may be concluded that Nitromint aerosol has a therapeutic action comparable to other short-acting nitrate preparations such as sublingual nitroglycerin tablet. According to the observations of the patients the drug action develops within a significantly shorter period. Considering the type of side-effects there was no difference between the two drug forms. Primarily, Nitromint tablet caused systemic effects (headache, dizziness, throbbing head) while aerosol caused predominantly local symptoms (burning of the tongue, disagreeable taste). These effects were only temporary and ceased within 10 minutes. According to the above described observations Nitromint aerosol may successfully be used as a new nitroglycerin containing drug form in all forms of angina pectoris: in rest angina, effort angina, as a prophylaxis, in mixed type angina pectoris, as a first-aid in emergency cases in acute left heart failure, preceding the application of infusion. PMID- 1585278 TI - How rapid is the return of fertility after the use of Tri-Regol oral contraceptive? AB - The study deals with the return of fertility following the discontinuance of the use of different oral contraceptives. On the basis of the evaluation of data of 222 cases the following were concluded: after the discontinuance of the use of oral contraceptives for a shorter-longer period delay may be observed in the return of fertility. This was not longer that 7 months in the evaluated cases. Compared to monophasic tablets, following the use of multiphasic tablets (Anteovin, Tri-Regol) regeneration, that is first ovulation and the following pregnancy, occur within a shorter period. The role of the duration of treatment in this delay could not be cleared because of the relatively low number of cases. Since, according to international data the post-pill return of fertility of nulliparas is slower than that of paras, the author highly recommends the use of multiphasic products for temporary contraception of nulliparas. PMID- 1585279 TI - Use of Tensiomin in hypertensive patients with impaired renal function. AB - Tensiomin treatment was applied in 20 hypertensive patients with impaired renal function but not requiring dialysis therapy and in 18 patients undergoing regular dialysis. In patients still not requiring dialysis the slowing down of the progression of renal failure, in the dialysed patients insufficient earlier therapy were the indications of Tensiomin treatment. Tensiomin was found to be an effective hypotensive drug in both groups, the majority of the side-effects were mild and of temporary character. The progression of renal failure was slower in the non-dialysed patients compared to the control group but the differences were statistically insignificant. PMID- 1585280 TI - Observations with Bromocriptin tablet. AB - Dopamine agonist Bromocriptin tablet has been used in 102 cases, partly for the inhibition of puerperal lactation, partly for the treatment of infertility accompanied by hyperprolactinaemia. On the basis of the clinical results and the changes of PRL level the drug was found to be very effective in both indications. Side-effects necessitating the discontinuance of treatment were not observed. PMID- 1585281 TI - Some possible gynaecological indications for peripheral antidopamine therapy. AB - The effect of the dopamine receptor blocking domperidone (Motilium) has been examined in 73 gynaecological patients in a wide indication field. The treatment was successful in controlling dyspeptic symptoms of different origins, nausea vomiting of different etiologies, climacteric flushes, and in the prevention of migraines in 67.1% of the cases. Partial response was obtained in 19.2%, and no response in 13.7% of the cases. According to the opinion of the authors the gastrokinetic and antiemetic effect of domperidone is of high value, the use of the drug may be attempted as a monotherapy or an adjuvant therapy for the prevention of migraine and the treatment of climacteric flushes. PMID- 1585282 TI - The theophylline dilemma. AB - The effectivity of recently introduced beta adrenergic agents in the USA prompted physicians to reevaluate the usefulness of theophylline having been used solely as a bronchodilator in the treatment of obstructive respiratory tract diseases. As part of a complex therapy applied in different diseases (acute asthmatic attacks, chronic asthma, acute exacerbation, and long-term treatment of obstructive bronchitis) theophylline is still a drug of value. The risk of toxicity can be reduced to a minimum. In the prevention of certain symptoms (e.g. nocturnal dyspnoea of asthmatics) (slow release) theophylline preparations proved to be the most advantageous. In aged patients technical difficulties limit the use of inhalation therapy, the oral applicability of theophylline is a further advantage of this product. PMID- 1585283 TI - Clinical observations with Paxirasol nasal spray. AB - The effect of Paxirasol nasal spray has been examined in 25 patients by the open method. The goal of the study was to assess and evaluate the clinical effectivity of the product and to observe the eventual side-effects. Among the examined patients 14 were acute and 11 chronic disease cases. In 20 of the 25 patients treated with Paxirasol nasal spray the pathological alteration of the nasal mucosa was controlled, mild alteration persisted in 4 patients, and moderately severe condition in 1 patient. The product significantly improved the viscosity of nasal discharge in all of them. The cessation or moderation of difficult nose blowing improved the general condition of the patients and accelerated recovery. Occasionally manifesting olfactory disorders ceased as well. The treatment needed not be discontinued because of the development of side-effects. Considering the healing tendency difference could be observed between the acute and chronic cases, especially in rhinitis sicca patients who were treated with Paxirasol nasal spray. In 23 of the 25 patients notable improvement of both the subjective and objective symptoms was observed. Paxirasol nasal spray is of value in very frequently occurring diseases of the nasal mucosa accompanied by dehydration. In the majority of acute disease patients the use of the product as monotherapy may result in complete cessation of symptoms. PMID- 1585284 TI - Tardyferon therapy in hyposiderosis of infancy and childhood. AB - In the majority of cases iron deficiency of infancy and early childhood is caused by nutritional factors. Among diseases, absorption disorders are the most frequent causes of iron deficiency. Tardyferon has been used for controlling iron deficiency in 21 children younger than two years of age not suffering from malabsorption and in 38 children suffering from coeliac disease. At the onset of the disease 71% of coeliac disease patients suffered from iron deficiency. The normalization of iron metabolism of these patients could be achieved with oral treatment of 5-6 mg Fe++/kg/day of 3-6 months. Iron deficiency of patients with initially normal ferritin level developed as a result of the intensive weight gain occurring in response to the gliadin-free diet. After the patients had been put on a gliadin containing diet again, hyposiderosis also occurred more frequently. Tardyferon therapy was well tolerated by the patients, in the infants taking bebe-Tardyferon difficulties of dosage or notable side-effects were not observed. PMID- 1585285 TI - Paul Zoll and the discovery of pacemaker. PMID- 1585286 TI - Examinations of the relative fluidity in cerebrovascular disease patients. AB - Parallel with the increasing incidence of cerebrovascular diseases, and the limitations of possible surgical methods, the importance of drug therapy has significantly increased. Due to our knowledge of haemorheology the effectiveness of therapies may be measured by means of useful circulatory markers. In course of our research activities of one and a half decades the changes in blood viscosity were measured during vinpocetine therapy, and were compared to the changes of haematocrit and mean corpuscular volume (MCV) values. The effect of vinpocetine and secale alkaloids or vinpocetine and pentoxifylline were compared by sequential analysis in other cases. The results of these examinations proved that vinpocetine is effective in both short and long-term therapy. PMID- 1585287 TI - Liposomes for controlled delivery of drugs to the lung. PMID- 1585288 TI - Cellular mechanisms of acute lung injury: implications for future treatment in the adult respiratory distress syndrome. PMID- 1585289 TI - New approaches to the rapid diagnosis of tuberculosis. PMID- 1585290 TI - Clinical value of the measurement of Mycobacterium tuberculosis specific antibody in pulmonary tuberculosis. AB - BACKGROUND: A serological test that could help to diagnose tuberculosis, especially smear negative disease, would contribute to patient management. METHODS: Levels of antibody to distinct antigens of Mycobacterium tuberculosis were assessed for their value in the diagnosis and management of pulmonary tuberculosis. Serum was taken from 52 patients who were smear positive, from 27 patients who were smear negative but with evidence of active tuberculosis (sputum culture positive in 16, response to antituberculosis chemotherapy in 11), from 11 patients with old healed tuberculosis (pre-antibiotic era), and from 39 healthy subjects vaccinated with BCG. RESULTS: In smear positive tuberculosis an enzyme linked immunosorbent assay using a single 38 kDa antigen gave a diagnostic sensitivity of 80% with a 100% specificity. In smear negative pulmonary tuberculosis, however, combination of the 19 kDa antigen, lipoarabinomannan (ML 34 epitope), and hsp 65 (TB 78 epitope) was needed to achieve a sensitivity of 64% with a specificity of 95%. Recurrent and extensive radiographic disease with a poor prognosis was associated with high anti-38 kDa and low anti-14 kDa antibody levels in patients with active disease. Patients with less pulmonary cavitation had high anti-19 kDa titres. Bacteriological relapse during treatment was indicated by a rise in anti-14 kDa (TB68 epitope) antibodies. Four patients with non-tuberculous mycobacterial infection showed no anti-38 kDa antibody. CONCLUSION: Antigen or epitope specific serology may help in the diagnosis, assessment of prognosis, and monitoring of chemotherapy in patients with pulmonary tuberculosis. PMID- 1585291 TI - Antibiotic treatment in pneumonia due to Q fever. AB - BACKGROUND: Whether Q fever responds better to doxycycline or erythromycin is unknown. METHODS: The efficacy of doxycycline and erythromycin in the treatment of pneumonia due to Q fever was assessed in a prospective, randomised, double blind study of 82 patients with a diagnosis of pneumonia and features suggestive of Q fever infection; 48 proved to have Q fever. Of the 48, 23 received doxycycline 100 mg twice a day and 25 patients received erythromycin 500 mg six hourly, both for 10 days. RESULTS: Both treatment groups had similar demographic characteristics. Fever showed a more rapid reduction in the doxycycline group (3(1.6) days versus 4.3(2) days). Side effects were observed in two patients receiving doxycycline compared with 11 patients receiving erythromycin (p less than 0.01). No differences were observed in other clinical or radiological measures. By day 40 the chest radiograph was normal in 47 of 48 patients. CONCLUSION: The results demonstrate the self limiting and benign nature of most cases of pneumonia due to Q fever. Doxycycline was more effective than erythromycin. PMID- 1585292 TI - Effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in the well elderly and in patients with chronic bronchitis. AB - BACKGROUND: Inhalation of the bacterial peptide N-formyl-methionyl-leucyl phenylalanine (FMLP) produces bronchoconstriction in normal subjects. FMLP thus has a putative role as a mediator of bronchoconstriction associated with bacterial bronchial infection. METHODS: The effects of FMLP inhalation were examined in ten subjects with a history of chronic bronchitis and ten age matched control subjects. Each subject inhaled FMLP doses from 0.025 to 0.8 mumol to determine the provocative dose of FMLP causing a 20% fall in FEV1(PD20FMLP). FEV1 was recorded every five minutes after the final FMLP inhalation until it had returned to 95% of baseline FEV1 or 60 minutes had elapsed. The time to return to 95% baseline FEV1 was recorded or extrapolated from the recovery curve as an index of rapidity of recovery. Total and differential white cell counts were performed on each subject at baseline and five and 15 minutes after the final FMLP inhalation. RESULTS: The geometric mean PD20 FMLP in the patients with chronic bronchitis was 0.06 mumol (95% confidence interval 0.015-0.26), which was significantly lower than that in the control subjects (0.21 mumol (0.02-1.9)). PD20 FMLP in the patients with chronic bronchitis but not age matched controls (p = 0.35) was lower than that found previously in young normal subjects (0.35 mumol (0.07-1.8). The return to 95% baseline FEV1 occurred after 86(10) minutes in subjects with chronic bronchitis and in 81(23) minutes in their age matched controls, in both cases being much slower than that seen in young subjects (29(9) minutes). CONCLUSION: Patients with chronic bronchitis may be especially susceptible to formyl peptides elaborated by bacteria during bacterial bronchial infection. PMID- 1585293 TI - Haematological effects of inhalation of N-formyl-methionyl-leucyl-phenylalanine in man. AB - BACKGROUND: N-Formyl-methionyl-leucyl-phenylalanine (FMLP) is a bacterial oligopeptide which stimulates neutrophil chemotaxis, degranulation and superoxide generation. Inhalation of FMLP produces bronchoconstriction in man; in the rabbit this is in part neutrophil dependent. The effects of inhalation of FMLP on peripheral blood leucocytes in normal subjects has been studied. METHODS: This was an open study in non-asthmatic subjects. Change in total peripheral white cell count were studied for 15 minutes after inhalation of 0.4 mumol FMLP in six subjects. Change in total and differential white cell count and spontaneous neutrophil chemiluminescence were then studied five and 30 minutes after inhalation of 0.4 mumol FMLP (n = 7) or diluent (n = 4). Finally, leucocytes from three subjects were labelled ex vivo with technetium-99m labelled sulphur colloid and reinfused. The effect of inhalation of FMLP or diluent on pulmonary neutrophil flux was studied by continuous gamma scanning of a pulmonary window. RESULTS: Leucopenia occurs rapidly after inhalation of FMLP, the nadir of the white cell count (53% of baseline) occurring at four minutes. This was followed by a rebound increase in white cell count evident at 15 minutes (154% of baseline). Five minutes after inhalation of 0.4 mumol FMLP, neutropenia (17% of baseline) and monocytopenia (40% of baseline) were seen followed again by a neutrophilia (213% of baseline at 30 minutes). The eosinophil count was significantly reduced at 30 minutes (24% of baseline). Neutrophil chemiluminescence was elevated (186% of baseline) at the time of the neutropenia. There was no influx of labelled cells to the lung during the period of neutropenia. CONCLUSION: FMLP inhalation activates circulating leucocytes. In vivo production of FMLP in the airway could contribute to bronchial inflammation during bacterial infection. PMID- 1585294 TI - Relation between the bronchial obstructive response to inhaled lipopolysaccharide and bronchial responsiveness to histamine. AB - BACKGROUND: Bronchoconstriction has developed after inhalation of lipopolysaccharide in a dose of 20 micrograms in asthmatic patients and of 200 micrograms in normal subjects. This study set out to determine whether the bronchial response to lipopolysaccharide was related to non-specific bronchial responsiveness and atopy. METHODS: Sixteen subjects with a fall in specific airway conductance of 40% (PD40sGaw) after inhaling up to 900 micrograms histamine inhaled 20 micrograms lipopolysaccharide (from Escherichia coli type 026:B6) a week after bronchial challenge with a control solution of saline. The bronchial response over five hours was measured as change in FEV1 and area under the FEV1-time curve. RESULTS: FEV1 fell significantly more after lipopolysaccharide than after diluent inhalation, the difference in mean (SE) FEV1 being 4.6% (5.4%); response was maximal 60 minutes after lipopolysaccharide inhalation and lasted more than five hours. Histamine PD20FEV1 and PD40sGaw correlated with the fall in FEV1 after lipopolysaccharide inhalation. There was no difference in the proportions of responders and non-responders to lipopolysaccharide who were atopic. CONCLUSION: Lipopolysaccharide induced bronchial obstruction is associated with non-specific responsiveness but not with atopy. PMID- 1585295 TI - Serial measurements of peak expiratory flow and responsiveness to methacholine in the diagnosis of aluminium potroom asthma. AB - BACKGROUND: Obstructive airways disease in aluminium potroom workers has been recognised for over 50 years. There is still controversy about whether this is true occupational asthma. METHODS: A cross sectional survey of 379 potroom workers identified 26 subjects with symptoms suggestive of occupational asthma. Of these 26, 14 were considered by the plant physician to have occupational asthma and had a measurable PC20 methacholine (provocative concentration causing a 20% fall in FEV1). These 14 were further investigated by serial measurements of peak flow at home and work, symptom diaries, and measurements of methacholine reactivity before and after a three week holiday. RESULTS: There was a good correlation between daily symptom scores and minimum peak flow measurements; these showed changes characteristic of occupational asthma in 10 workers, with increased diurnal variation in peak flow and consistent deterioration in relation to work exposure. One further record showed probable occupational asthma and two showed consistent small changes in peak flow related to work exposure more in keeping with an irritant effect. Only one record was inadequate. Methacholine reactivity on a work day was within the normal range in nine of 13 subjects. A doubling of PC20 methacholine occurred in five of nine subjects with occupational asthma in whom repeated estimations were possible. CONCLUSIONS: This study confirms the existence of aluminium potroom asthma. The lack of correlation with measurements of non-specific responsiveness suggests that the primary mechanism is one of hypersensitivity, perhaps enhanced by the bronchial irritants also present in the potroom. PMID- 1585296 TI - Effect of temazepam on tracheobronchial mucus clearance. AB - BACKGROUND: Tracheobronchial clearance of mucus from the lungs is reduced during sleep and, usually, by the administration of opiates. It seemed possible therefore that temazepam, a widely used potent benzodiazepine, retarded clearance. METHODS: The effect of 10 mg temazepam on mucociliary clearance was studied in eight healthy volunteers, aged 18-50 (mean 30) years, in a randomised, placebo controlled, double blind, cross-over study. Six subjects were female and two male. Six were non-smokers and two were light current smokers. Clearance was assessed from the change in radio-activity in the lungs after inhalation of 5 microns diameter polystyrene particles, labelled with technetium-99m, under controlled conditions. RESULTS: Tracheobronchial clearance was reduced by 22% after temazepam by comparison with placebo during the first three hours after drug ingestion; this is the period when circulating drug concentrations are highest. CONCLUSION: Temazepam should be prescribed with caution in patients with impaired lung mucociliary transport. PMID- 1585297 TI - AIDS and the lung: update 1992. 1. Pneumocystis carinii pneumonia. PMID- 1585298 TI - Recent advances in somatic gene therapy for hereditary respiratory diseases. PMID- 1585299 TI - Forced oscillation techniques for measuring mechanical properties of the respiratory system. PMID- 1585300 TI - Fatal mediastinal compression as a late complication of surgical plombage. AB - Surgical plombage was used as a form of collapse therapy for pulmonary tuberculosis before the advent of reliable chemotherapy. A patient developed stridor, recurrent laryngeal nerve paralysis, and obstruction of the superior vena cava and eventually died as a result of haemorrhage into a large intrathoracic cyst, secondary to a polystan pack inserted 38 years previously. PMID- 1585301 TI - Diffuse interstitial lung disease due to AA amyloidosis. AB - A man developed interstitial lung disease and nephrotic syndrome due to AA amyloidosis. There was no evidence of an underlying disease predisposing to amyloidosis. PMID- 1585302 TI - Thoracic duct cyst in the mediastinum. AB - A thoracic duct cyst was excised from the mediastinum of an 86 year old man. It had caused acute respiratory failure through compression of the trachea. PMID- 1585303 TI - Tuberculosis in the Third World. PMID- 1585304 TI - Cystic fibrosis: current survival and population estimates to the year 2000. PMID- 1585305 TI - Invasive aspergillosis in a patient with idiopathic thrombocytopenic purpura without underlying lung disease. PMID- 1585306 TI - Current concepts in the diagnosis of liver disease in the dog and cat. PMID- 1585307 TI - Fine needle aspiration biopsy of the liver, a new tool in the diagnosis of liver disease. PMID- 1585308 TI - Accumulation of copper and iron in the liver of a boxer: a new disease? PMID- 1585309 TI - Blood transfusions in the dog and cat. PMID- 1585310 TI - Per- and perioperative fluid therapy guided by (arterial) blood pressure measurements. PMID- 1585311 TI - Ways to administer fluids. Practical parenteral and enteral techniques. PMID- 1585312 TI - Treatment of anemic birds with iron dextran therapy: homologous and heterologous blood transfusions. PMID- 1585313 TI - Clinical dermatology of dogs and cats. PMID- 1585314 TI - Feline AIDS: symptoms and treatment. PMID- 1585315 TI - Thyroid cancer research in the dog: anno 1992. PMID- 1585316 TI - Clinical trial on sustained-release phenytoin. Preliminary results of the open, non-controlled study. The Phenytoin Trial Group on Canine Epilepsy. PMID- 1585317 TI - Adrenalectomy in 36 dogs and 2 cats with hyperadrenocorticism. PMID- 1585318 TI - The treatment of recurrent abscessation in the neck region of the dog, evaluation of 35 patients. PMID- 1585319 TI - Persistent mullerian duct syndrome in the basset hound. PMID- 1585320 TI - Diagnosis of canine prostatic carcinoma. PMID- 1585321 TI - Diagnosis and conservative treatment of hip dysplasia in young dogs. PMID- 1585322 TI - Surgical therapy for canine hip dysplasia. PMID- 1585323 TI - Triple pelvic osteotomy: radiological results of 38 cases. PMID- 1585324 TI - Differential diagnosis of hip dysplasia. PMID- 1585325 TI - Coxofemoral luxation in dogs and cats: surgical technique and results of an extra articular technique. PMID- 1585326 TI - Ocular filariasis in a parakeet, a tropical surprise. PMID- 1585327 TI - Periodontal disease in dogs and cats. PMID- 1585328 TI - Radiographic diagnosis of tumors. PMID- 1585329 TI - Diagnostic imaging of the liver in dogs. PMID- 1585330 TI - Canine malignant histiocytosis (MH): clinical and radiographic findings. PMID- 1585331 TI - Obesity treatment and prevention in companion animals. PMID- 1585332 TI - Surgical nutrition and nutritional aspects of wound healing. PMID- 1585333 TI - Practical advances in nutritional support of the sick and injured cat. PMID- 1585334 TI - Social behaviour of the domestic dog. PMID- 1585335 TI - The establishment of dominance relationships in a dog pack and its relevance for the man-dog relationship. PMID- 1585336 TI - Stress and welfare and its parameters in dogs. PMID- 1585337 TI - Social behaviour of cats. PMID- 1585338 TI - The influence of companion animals on the physical and psychological well-being of humans. PMID- 1585339 TI - High impact communications via psycho-geometrics. PMID- 1585340 TI - Professionalism in the veterinary practice. PMID- 1585341 TI - An approach to the patient with gastrointestinal disease and the formulation of a differential diagnosis. PMID- 1585342 TI - Treatment of gastrointestinal disease in the dog and cat. PMID- 1585343 TI - The effects of radical scavengers and leukocyte-depleted blood on reperfusion injury of extirpated rabbit lung. AB - Oxygen radicals produced by polymorphonuclear leukocytes were considered primarily responsible for reperfusion injury in lung transplantation. Using the extirpated rabbit lungs as a transplant model, we measured lung water volume, the oxygen radicals of lung tissue using a direct method (electron spin resonance) and an indirect method (measurement of peroxide lipids). The effects of free radical scavengers, human superoxide dismutase (h-SOD) and catalase (CAT), and leukocyte-depleted blood on reperfusion injury were evaluated in three experimental groups. Group I (n = 8, control): Lung reperfusion was performed with blood from other rabbits. Group II (n = 7): Immediately before reperfusion, h-SOD (1,500 u/ml) and CAT (3,000 u/ml) were added to the blood. Group III (n = 7): Reperfusion was performed with the leukocyte-depleted blood. Severe pulmonary edema and an elevation of malondialdehyde (MDA) occurred in Group I. In Group II, addition of radical scavengers to the reperfusion blood produced only mild pulmonary edema, but an elevation of MDA occurred as in Group I. In Group III, pulmonary edema and MDA elevation were almost completely suppressed. PMID- 1585345 TI - Computer-assisted gait training (CAGT) of hemiparetic stroke patients: whose recovery is most predictable? AB - Maximum walking speed for 10 m distance of 109 hemiparetic stroke patients was examined every week for 7 weeks after starting computer-assisted gait training (CAGT), and the relation between the time since stroke onset (x) and the maximum walking speed (y) was approximated by a hyperbolic function, y = A-B/x. The patients were divided into two groups, 91 cases with a significant fit of the function (fit group) and 18 without fit (non-fit). The gain of maximum walking speed during 7 weeks was larger in the fit group, compared to the non-fit. Computed tomography examination revealed that the significant fit was mostly expected in patients with the caspular lesion without the cortical involvements except the frontal. The time at which the maximum walking speed of the patients belonging to the fit group would reach the midst of the estimated full recovery of gait can be predicted at the start of CAGT (R2 = 0.955), using two variables: the time since stroke onset and the maximum walking speed. PMID- 1585344 TI - Is there any effect of volcanic eruptions of Mount Sakurajima on human lungs?- histopathological investigation and measurement of intrapulmonary particulate deposits amounts. AB - In order to investigate effects of volcanic eruptions of Mt. Sakurajima on human lungs, an amount of intrapulmonary particulate deposits (IPD) and histopathological changes were evaluated, using autopsied lungs of deceased residents of Kagoshima (the area affected most by the volcanic eruptions of Mt. Sakurajima, n = 66) in comparison with those of Saitama (n = 73). The amount of IPD was measured by macroscopic image analysis and by alkaline extraction. Correlation was seen in the IPD values obtained by these two methods (Spearman's correlation coefficient: 0.525). The IPD value measured through chemical digestion, which increased with age, was lower in the residents of Kagoshima (17.0 +/- 6.3 mg/g) than in those of Saitama (26.8 +/- 10.6 mg/g). This difference of IPD value between Kagoshima and Saitama residents was also observed in male, female, smoker and nonsmoker subgroups. The incidence of pulmonary emphysema was not different between Kagoshima and Saitama cases. No silicotic nodules were observed in any cases. But, the incidence of bronchial goblet cell hyperplasia and squamous metaplasia in Kagoshima was higher than that in Saitama in male cases and smoker cases. In Kagoshima cases, the incidence of squamous metaplasia was significantly higher in smokers than in nonsmokers. The synergistic influence of volcanic eruptions and cigarette smoking on human airways was suggested. PMID- 1585346 TI - Scanning electron microscopic study on the three-dimensional structure of the collagen fibrillar framework in the chronic active hepatitis and liver cirrhosis. AB - The three-dimensional collagen framework of human liver parenchyma in surgical specimens from patients with chronic active hepatitis (CAH), viral or alcoholic cirrhoses (LC) was observed by scanning electron microscopy after cell-maceration by the method of Ohtani (1988). In control livers, the tubular sheaths of collagen fibers housing the sinusoid were shown to form a labyrinthine network, which we called the perisinusoidal collagen sheaths (PSCSs), and a loose band like collagen sheath was seen embracing each hepatocyte, which we called the perihepatocellular collagen sheath (PHCS). In CAH, thin septa partially surrounded the lobules, but the PHCS and PSCS appeared almost unchanged. In viral LC, thick collagen septa surrounded pseudolobules of various sizes. In these conditions, the collagen density was slight in PSCSs, while in PHCSs, it was prominent and associated with an enlargement of sheaths themselves. In alcoholic LC of mixed type, the basic structure of the collagen framework closely imitated that of viral LC. PMID- 1585347 TI - Three-lineage hemopoietic precursor cells and effectiveness of recombinant human erythropoietin in patients with myelodysplastic syndromes. AB - Four-stem-cell assays, which evaluate megakaryocytic (CFU-Meg), immature and mature erythropoietic (BFU-E, CFU-E), and granulocyte-macrophage (CFU-GM) colony formation, were performed in nine patients with myelodysplastic syndromes (MDS). The CFU-Meg, BFU-E, and CFU-E colony growths were disturbed more often than the CFU-GM colony formation. A CFU-E increase was not recognized in most MDS patients, but a dose-dependent increase of bone marrow CFU-Es in response to erythropoietin (EPO) was recognized only in two refractory anemia (RA) patients whose CFU-Es were more than one tenth of normal controls. One patient with RA and the other with chronic myelomonocytic leukemia (CMML), both of whose bone marrow CFU-Es did not increase at the higher dose of EPO in vitro, were treated with recombinant human EPO (rHuEPO), resulting in no effects. The responsiveness of patients with MDS to various recombinant hemopoietic factors might be predicted by both the residual degree of bone marrow hematopoietic precursor cells and the response of stem cells to the higher doses of each hemopoietic factor. PMID- 1585348 TI - Peritoneal cytology in endometrial carcinoma. AB - Peritoneal cytology is accepted as part of the evaluation for patients undergoing laparotomy for a suspected or proven gynecologic malignancy. The study subjects were 83 patients with endometrial carcinoma. We investigated the significance of peritoneal cytology in endometrial carcinoma. Cytological positive results were observed in 11 (23%) of the 48 T1 cases, 9 (50%) of the 18 T2 cases and 4 (50%) of the 8 T3 cases. Cytological positive rates by histological differentiations were 14 (28%) for 50 G1 cases, 4 (36%) for 11 G2 cases and 6 (46%) for 13 G3 cases. Cytological positive results were found in 11 (28%) of 39 cases of less than 1/3 of intramuscular infiltration and 13 (37%) of 35 cases of 1/3 or more infiltration. Five (56%) of 9 metastasis cases and 17 (29%) of 59 nonmetastasis cases were found positive cytologically. An analysis of the data indicated that the influence of positive peritoneal cytology on recurrence superceded that of other known risk factors, such as grade, myometrial invasion, extrauterine disease, and lymph node metastasis. The patients with normal cytological findings at laparotomy tend to have a significantly (p less than 0.01) better prognosis than similar patients with abnormal cytological findings. PMID- 1585349 TI - Intraoperative radiation therapy combined with hyperthermia against pancreatic carcinoma. AB - Fourteen patients with pancreatic carcinoma were treated by intraoperative radiation therapy (IORT) combined with hyperthermia (hyperthermia group). Their treatment results were compared with those of fifty five patients treated by IORT without hyperthermia (control group). Most of patients underwent some kind of chemotherapy for the carcinoma and some of them received post-operative irradiation. Although there was no significant difference in pain relief between hyperthermia group and control group, the local tumor control rate of the former group was a little better. The survival rate of all patients was 14.5% at one year, 2.9% at two years, 2.9% at three years and 0% at four years after surgery. The survival rate of the hyperthermia group was 21.4% at one year and 7.1% at two years and that of the control group was 12.7% at one year and 1.8% at two years. The survival of the hyperthermia group was a little better than that of control group, but the difference was not significant. Only 36% of patients of hyperthermia group were successfully heated, and if hyperthermia were given successfully to all patients, their prognoses would be possibly improved. PMID- 1585350 TI - Business planning: who, what, when, where, why, and how. PMID- 1585351 TI - Health care business planning. PMID- 1585352 TI - Planning roadblocks and detours. PMID- 1585353 TI - A process for service transformation in the evolving health care field. PMID- 1585354 TI - Marketing to consumers: unleashing technologies to help the public choose health service options. PMID- 1585355 TI - Planning in today's environment: an empirical study. PMID- 1585356 TI - Multihospital systems: the turning point. PMID- 1585357 TI - Planning process at Northwestern Memorial Hospital. PMID- 1585358 TI - Planning an alternative delivery system. PMID- 1585359 TI - Market and financial planning in senior care. PMID- 1585360 TI - Physician assessment of office-based technologies. PMID- 1585361 TI - Financial planning for hospitals. PMID- 1585362 TI - Pharmacokinetics, metabolic activation, and lung toxicity of cyclophosphamide in C57/B16 and ICR mice. AB - A single intraperitoneal dose (200 mg/kg) of cyclophosphamide (CP) resulted in significantly less injury to the C57/B16 strain than to the ICR strain of mice. Maximal thymidine incorporation into total lung DNA, an indirect index of lung injury, and pulmonary hydroxyproline content, a marker of fibrosis, were 56 +/- 10% and 69 +/- 9 of ICR mice, respectively. Pharmacokinetics and metabolism of [side chain-3H]CP and [ring-14C]CP were assessed in vivo. In addition, covalent binding and the generation of polar metabolites were determined in hepatic and pulmonary microsomes from both strains. Peak levels and half-lives of radioactivity derived from CP in blood were similar in both strains treated with a 200 mg/kg dose. However, area under curve for total radioactivity over 12 hr was significantly lower (60 and 78% of ICR for 3H and 14C, respectively), and systemic clearance significantly higher (168 and 119% of ICR for 3H and 14C, respectively) in the C57 strain. Total radioactivity derived from CP in lung and liver was similar between strains at all time points examined up to 12 hr, but overall covalent binding of radioactivity, assessed as area under the binding curve, was markedly lower to C57 lungs in vivo (58 and 49% of ICR for 3H and 14C, respectively). In contrast, hepatic binding was not significantly different between strains with either label. No significant differences were evident between strains in hepatic or pulmonary microsomal binding in vitro. Polar CP metabolites in ICR lung were significantly higher than C57 at 2 hr in vivo, but no strain differences were evident at other times nor in the microsomal generation of polar metabolites. These results demonstrate significant differences in the pharmacokinetics of CP between C57 and ICR murine strains. NADPH-mediated activation of CP in vitro was similar between strains suggesting that the increased covalent binding of CP to ICR lung tissue in vivo was due to greater exposure to CP or its reactive metabolites. The relative resistance of C57 mice to CP-induced lung fibrosis may also be influenced by intrinsic differences in response of the lung to reactive CP species, or by differences in activation by other metabolic pathways. PMID- 1585363 TI - In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p dioxin. 2. Effects on sexual behavior and the regulation of luteinizing hormone secretion in adulthood. AB - When administered to postpubescent male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could impair sexual differentiation of the central nervous system (CNS) and thereby alter male reproductive function. To examine this possibility, sexually dimorphic functions were assessed in male rats born to dams given TCDD (0.064, 0.16, 0.40, and 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation. Masculine sexual behavior was assessed at approximately 60, 75, and 115 days of age. When TCDD-exposed males were caged with receptive control females their mount, intromission, and ejaculation latencies were far longer than normal; these effects were dose related and were statistically significant at maternal doses as low as 0.16, 0.064, and 0.16 micrograms TCDD/kg, respectively. The numbers of mounts and intromissions to ejaculation were slightly increased by TCDD, while copulatory rates [(mounts+intromissions)/min] were significantly decreased at the three highest maternal doses. Except for a modest increase at the higher doses, TCDD had little effect on the postejaculatory interval. Following assessment of their masculine sexual behavior, the males were castrated and 6 weeks later tested for feminine sexual behavior (lordosis). After being primed with estradiol benzoate and treated with progesterone, males displayed dose-related increases in lordosis quotient and lordosis intensity in response to being mounted by another male. These effects were statistically significant at maternal doses as low as 0.16 and 0.40 micrograms TCDD/kg, respectively. To determine if perinatal TCDD exposure alters the sexually dimorphic regulation of luteinizing hormone (LH) secretion, the LH secretory responsiveness of the hypothalamic/pituitary axis to ovarian steroids was assessed. In unexposed, gonadectomized female rats primed with estradiol benzoate, progesterone injection produced a surge in plasma LH concentrations, whereas in similarly treated control males, plasma LH concentrations were unaffected by progesterone. In castrated, estradiol benzoate primed male rats that were perinatally exposed to TCDD, progesterone treatment produced dose-related increases in plasma LH concentrations that were statistically significant at the two highest maternal doses. We conclude that in utero and lactational exposure to small amounts of TCDD demasculinizes and feminizes male rats. These effects cannot be accounted for by TCDD-induced hypophagia, modest reductions in adult plasma androgen concentrations, possible nonspecific changes in motor activity, or possible reductions in penile sensitivity to sexual stimulation. The altered sexual behaviors and LH secretion were observed when nearly all TCDD had been excreted (as evidenced by uninduced hepatic ethoxyresorufin-O-deethylase activity).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1585364 TI - In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p dioxin. 3. Effects on spermatogenesis and reproductive capability. AB - When administered in overtly toxic doses to postweanling male rats, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1585365 TI - Effects of sodium arsenite on the cytoskeleton and cellular glutathione levels in cultured cells. AB - The effects of As3+ (NaAsO2) on the microtubule and microfilament organization, cytoskeletal protein synthesis, cytoskeletal and cytosolic (soluble) protein sulfhydryls, and cellular glutathione (GSH) levels were examined in Swiss 3T3 mouse cells. Exposure of cells to 2.5 microM As3+ for 16 hr resulted in apparent cell retraction and loss of thick cables of actin filaments. However, the cells still retained numerous thinner microfilaments distributed in a disorganized manner. Microtubule organization was relatively undisturbed. At higher doses (greater than or equal to 20 microM), As3+ treatment caused a severe loss of microtubules and the remaining dense finer actin filaments formed smearing clusters in perinuclear areas. Treatment of cells with As3+ also induced a dose dependent inhibition of cytoskeletal protein synthesis. Furthermore, As3+ exposure enhanced cellular GSH synthesis since the elevated cellular GSH content in As(3+)-treated cells could be abolished by treatment with buthionine sulfoximine, an inhibitor of gamma-glutamylcysteine synthetase required for GSH biosynthesis. As determined by the N-[3H]-ethylmaleimide binding assay, As3+ exposure also increased the amount of protein sulfhydryls in both the cytoskeletal and the cytosolic protein fractions. Moreover, a greater increase in protein sulfhydryls occurred in the cytoskeletal fraction than in the soluble fraction. These results indicate that the cytoskeleton could be a cellular target for injury by As3+ exposure. The elevated cellular GSH content induced by As3+ could provide a protective mechanism against further injury from this metal insult. PMID- 1585366 TI - Upper respiratory tract deposition of inspired acetaldehyde. AB - Inhalation exposure of rodents to high concentrations of acetaldehyde produces lesions in the upper respiratory tract (URT, all regions of the respiratory tract anterior to and including the larynx). Information on the inhalation dosimetric relationships for this vapor are needed for a comprehensive understanding of its inhalation toxicity. Toward this end, uptake of acetaldehyde was measured in the surgically isolated URT of the urethane-anesthetized male F344 rat under unidirectional (50, 100, 200, or 300 ml/min) and cyclic (100 ml/min) flow conditions at inspired concentrations of 1, 10, 100, or 1000 ppm. Under all flow conditions URT deposition efficiency was strongly dependent on inspired concentration. URT deposition efficiency (under cyclic flow) averaged 76, 48, 41, and 26% at 1, 10, 100, and 1000 ppm, respectively. Nasal acetaldehyde dehydrogenase activity averaged 1.2 micrograms/min. Absolute acetaldehyde deposition rates (micrograms/min) at 100 and 1000 ppm exceeded this activity by 5 to 100-fold, suggesting a possible mechanism for the reduced deposition efficiency at high concentrations. URT deposition under unidirectional flow was strongly dependent on the inspiratory flow rate. The effect of flow rate on deposition was reasonably predicted by the mass-transfer model of Aharonson et al. (J. Appl. Physiol. 37, 654-657, 1974). The uptake coefficients determined from the unidirectional flow studies were used to predict uptake under cyclic flow by integration of the model. The predicted cyclic deposition efficiencies differed from the observed efficiencies by 2.3 +/- 4.3% (mean +/- SEM), suggesting this model might provide a reasonable first approximation for acetaldehyde uptake under cyclic breathing conditions. PMID- 1585367 TI - Metabolism of trans,trans-muconaldehyde by aldehyde and alcohol dehydrogenases: identification of a novel metabolite. AB - The metabolism of trans,trans-muconaldehyde (MA), a highly reactive alpha,beta unsaturated dialdehyde, was examined in vitro using purified yeast alcohol and aldehyde dehydrogenases (ADH and ALDH, respectively). In the presence of NAD(+) fortified ALDH, the mono-oxidation product (acid/aldehyde) was the primary metabolite formed with trace amounts of the dioxidation product (trans,trans muconic acid). In NADH-fortified reactions with ADH, both the mono- and direduction products (hydroxy/aldehyde and dihydroxy, respectively) were readily detected. Oxidation and reduction products of MA were formed in incubates containing both dehydrogenases together with either NAD+ or NADH. Unexpectedly, an additional metabolite was detected, which was a major product in both NAD(+)- and NADH-fortified systems containing ALDH and ADH in combination and whose formation could be inhibited by pyrazole (an ADH inhibitor). ALDH-mediated oxidation of a synthetic standard of the hydroxy/aldehyde derivative of MA resulted in formation of this new metabolite, which was also a major product formed by rat hepatocytes incubated with MA. Using HPLC/photodiode array detection, the new metabolite was found to cochromatograph and have a uv spectrum identical to that of a synthetic standard of the hydroxy/acid derivative of MA. The metabolite was confirmed as the hydroxy/acid derivative of MA after preparative HPLC, TMS derivatization, and GC/MS analysis. The hydroxy/acid metabolite was not formed during ADH-mediated reduction of the mono-oxidation product of MA, suggesting that this metabolite was formed by yeast dehydrogenases via a primary reduction of MA and subsequent oxidation of the hydroxy/aldehyde to the hydroxy/acid. These data show that the hydroxy/acid derivative is a novel metabolite of MA, which arises from the interaction of both oxidative and reductive routes of metabolism. PMID- 1585368 TI - Persistent effects of a single dose of Aroclor 1254 on cytochromes P450IA1 and IIB1 in mouse lung. AB - The polychlorinated biphenyl mixture Aroclor 1254 has been shown to elicit prolonged biochemical responses in several rodent species, particularly induction of mixed function oxygenases in hepatic tissue. Lung is also of interest since a single dose of Aroclor 1254 has been demonstrated to have a tumor promoting effect, increasing the numbers of lung tumors in Swiss mice initiated with N nitrosodimethylamine. To investigate the enzyme induction response in lung, male Swiss mice were given a single 100 or 500 mg/kg dose of Aroclor 1254 and euthanized at time intervals ranging from 48 hr to 30 weeks. Both cytochromes P450IA1 and IIB1 were followed by use of specific enzyme activities and Western immunoblotting. The IA1 isoform, as quantified by ethoxyresorufin-O-deethylase activity and immunoblotting with monoclonal antibody 1-7-1, was significantly elevated for 30 weeks after both doses. In contrast, benzyloxy-resorufin-O dealkylase activity (P450IIB1 specific), which is constitutively expressed in rodent lung, was unaffected by Aroclor treatment at the lower dose at early time points, but induced twofold at 30 weeks. At the higher dose, however, enzymatic activity was decreased to 50% of control values, an effect which persisted for 4 weeks postexposure. These changes were confirmed by Western immunoblotting utilizing monoclonal antibody 2-66-3. Concomitantly, content of individual PCB congeners in lungs and carcass was quantified by gas chromatography with electron capture detection. One congener, 2,3,3',4,4'-pentachlorobiphenyl, was selectively retained in lung compared to carcass. Lack of correlation between changes in lung content of PCBs and levels of the P450 isoforms suggested interactions between congeners in control of P450 induction and repression. These data confirm a prolonged P450 induction response in nonhepatic tissue following Aroclor exposure, and further suggest a bidirectional role for certain PCB congeners in the regulation of P450IA1 and P450IIB1 expression in lung tissue. PMID- 1585369 TI - Dichloromethane (methylene chloride): metabolism to formaldehyde and formation of DNA-protein cross-links in B6C3F1 mice and Syrian golden hamsters. AB - Dichloromethane (DCM) is metabolized via a glutathione transferase (GST) dependent pathway to formaldehyde (HCHO), a mutagenic compound that could play an important role in the carcinogenic effects of DCM observed in the liver and lungs of B6C3F1 mice at 2000 and 4000 ppm. Syrian hamsters metabolize DCM more slowly than mice via this pathway, and hamsters exposed to 3500 ppm showed no apparent carcinogenic response. The possible formation of DNA-protein cross-links (DPX) from DCM in both species was examined. Male mice and hamsters were pre-exposed for 2 days (6 hr/day) to 4000 ppm of DCM and on the third day were exposed (6 hr) to a decaying concentration (4500 to 2500 ppm) of [14C]DCM. DPX were detected in mouse liver, but not in mouse lung, hamster liver, or hamster lung. The failure to detect DPX in mouse lung does not exclude their possible formation in a subpopulation of lung cells. Metabolic incorporation of 14C derived from [14C]DCM into DNA suggested a higher rate of turnover of some mouse lung cells than of hamster lung cells, but no large difference in the turnover rates of liver cells in the two species under these conditions. These results demonstrate that HCHO derived from DCM can form DNA-protein cross-links in the liver of the B6C3F1 mouse. The formation of DPX is dependent on the activity of the GST pathway, and species such as hamsters and humans having much lower rates of DCM metabolism via this pathway may not generate toxicologically significant concentrations of HCHO and DPX. PMID- 1585370 TI - A common viral infection can change nickel target organ distribution. AB - The autoradiographic distribution of the toxic heavy metal nickel (Ni) was studied at 4 and 7 days post-coxsackievirus B3 (CB3) infection in Balb/c mice. The distribution of the iv injected 63Ni was studied 10 min, 4 hr, and 24 hr after administration. Results clearly show that the site of 63Ni accumulation is greatly changed during this viral infection. This newly discovered distribution was mainly visible as a greatly increased accumulation in the pancreas and the wall of the ventricular myocardium. Healthy animals showed almost no 63Ni accumulation in these tissues. These results for the first time show that an invading microorganism can change the distribution of an environmental pollutant. PMID- 1585371 TI - Acute stimulation of trifluoroethene defluorination and cytochrome P450 inactivation in the rat by exposure to isoflurane. AB - The effect of isoflurane on trifluoroethene (TFE) defluorination and cytochrome P450 inactivation was examined in rats to determine the influence of this anesthetic on in vivo fluoroethene metabolism. Exposure of rats to TFE (0.5%, v/v) or a mixture of TFE and isoflurane (0.5% each) in oxygen for 60 min resulted in plasma fluoride increased over that in nonexposed or isoflurane (0.5%)-exposed animals. In untreated rats plasma fluoride levels following TFE and TFE isoflurane exposures were approximately equal. In rats treated with phenobarbital, however, isoflurane increased plasma fluoride over two times that in rats exposed to TFE alone. Likewise cytochrome P450 levels declined 24% in TFE exposed animals and 64% in rats exposed to TFE-isoflurane. The ability of microsomes from fluorocarbon-exposed animals to metabolize (R)- and (S)-warfarin indicates that TFE exposure inactivated the phenobarbital-inducible isozymes P450IIB1, P450IIC6, and P450IIIA to approximately equal degrees (21-35%). TFE isoflurane exposure further inhibited P450IIB1 and PB450IIC6 to 50-70%, but had only a minor effect on P450IIIA activity. These data demonstrate that the defluorination of TFE in vivo by the phenobarbital-inducible cytochrome P450 isozymes is increased by isoflurane, and that isoflurane enhances the ability of TFE to inactivate cytochromes P450 in an isozyme-selective manner. PMID- 1585372 TI - Effects of glutathione-modulating agents on the covalent binding and toxicity of dichlobenil in the mouse olfactory mucosa. AB - Twenty-four hours following injection of a single dose of the herbicide dichlobenil (2,6-dichlorobenzonitrile) in C57Bl/6 mice a steep dose-response curve for the histopathological toxicity in the olfactory mucosa was observed. Four hours following injection of a toxic dose of [ring-14C]dichlobenil (12 mg/kg) the covalent binding in the olfactory mucosa was 26 times higher than that in the liver. A dose-dependent decrease of nonprotein sulfhydryls (mainly glutathione, GSH) in the olfactory mucosa was observed 2.5 hr following injection of dichlobenil (6, 12, 25 mg/kg). The synthetic GSH precursor N-acetyl-L-cysteine decreased both the dichlobenil-induced toxicity and the covalent binding, whereas N-acetyl-D-cysteine had no effect. No protective effects of the cyanide antidotes nitrite, thiosulfate, or superoxide dismutase on the dichlobenil-induced toxicity were observed. In mice given the GSH-depleting agent phorone and a subtoxic dose of dichlobenil (6 mg/kg), an extensive toxicity and an increased covalent binding in the olfactory mucosa were demonstrated. Autoradiography showed no change in the distribution of covalent [14C]dichlobenil binding to nontarget tissues of phorone-treated mice. In conclusion, the results demonstrate a relationship between the degrees of covalent binding, GSH depletion, and toxicity of dichlobenil in the olfactory mucosa. Hence, the level of GSH appears to be of importance for the dichlobenil-induced toxicity in the olfactory mucosa. PMID- 1585373 TI - Lead perturbs epidermal growth factor (EGF) modulation of intracellular calcium metabolism and collagen synthesis in clonal rat osteoblastic (ROS 17/2.8) cells. AB - EGF, a single-chain polypeptide growth factor important for many cellular functions including glycolysis and protein phosphorylation, is known to modulate calcium metabolism in several cell systems. EGF causes an increase in Ca2+ influx and accumulation of inositol triphosphate and probably exhibits many, if not all, of its effects via the calcium messenger system. Lead is known to interact with and perturb normal calcium signaling pathways; therefore, the purpose of this work was to determine if lead perturbs EGF modulation of calcium metabolism in ROS 17/2.8 cells and if lead impairs collagen synthesis, which is controlled by EGF. To characterize 45Ca kinetics, cells were labelled with 45Ca (1.87 mM Ca) for 20 hr in the presence of 5 microM Pb, 50 ng/ml EGF, or 5 microM Pb and 50 ng/ml EGF. Kinetic parameters were determined from 45Ca efflux curves. Three kinetic compartments described the intracellular metabolism of 45Ca; 5 microM Pb significantly altered the effect of EGF on intracellular calcium metabolism. Calcium distribution was shifted from the fast-exchanging, quantitatively small calcium pools S1 and S2 to the slow-exchanging, quantitatively large S3. There was also a 50% increase in total cell calcium in cells treated with 5 microM Pb and 50 ng/ml EGF over calcium in cells treated with 50 ng/ml EGF alone. Because EGF and phorbol 12-myristate 13-acetate (PMA) have similar effects on protein kinase C (PKC) and collagen metabolism, the transient effects of EGF and PMA on 45Ca and 210Pb were also characterized. EGF caused a rapid transient increase in efflux of both isotopes, which was further increased by the addition of PMA. In contrast, PMA pretreatment, which depletes PKC, significantly attenuated the latter effect of EGF, suggesting that downregulation by PKC of EGF-induced increases in 45Ca and 210Pb efflux. Moreover, collagen synthesis was decreased by lead, EGF, and PMA in a similar manner, further suggesting PKC as the common modulator of these effects. These data show that Pb impairs the normal modulation of intracellular calcium homeostasis and collagen synthesis by EGF. Furthermore, these results provide additional support to the postulate that an early and discrete effect of lead involves perturbation of the calcium messenger system at one or several loci. PMID- 1585374 TI - alpha-Naphthyl butyrate carboxylesterase activity in human and rat nasal tissue. AB - Carboxylesterase activity in the rat nasal mucosa plays an important role in the response of this tissue to certain toxic inhaled esters. We have examined this activity in extracts of both Fischer-344 rat and human nasal tissue using the substrate alpha-naphthyl butyrate, the same substrate as that used for histochemical analysis of this activity. We find substantially higher activity in rat nasal extracts than in human nasal extracts. The Michaelis constant (Km), however, is approximately the same for both activities and is significantly less than that reported for rat nasal carboxylesterase activity using dibasic esters as a substrate. p-Nitrophenyl butyrate is a competitive inhibitor of the rat alpha-naphthyl butyrate esterase, but surprisingly has no effect on the human activity. The assay reported here should prove a powerful tool in the development of a valid in vitro nasal toxicity assay system that uses cultured rat or human cells expressing carboxylesterase activity. PMID- 1585375 TI - 2-Methoxyacetic acid dosimetry-teratogenicity relationships in CD-1 mice exposed to 2-methoxyethanol. AB - The teratogen 2-methoxyethanol (2-ME), an industrial solvent, was administered to pregnant CD-1 mice either as a single subcutaneous (sc) bolus dose (100-250 mg/kg) or via constant-rate infusion from sc implanted osmotic minipumps (34.7 or 69.4 mg/kg/hr for up to 12 hr) on gestation Day 11, when embryonic paw development is maximally sensitive to perturbation by this agent. The sc entry route most closely reflects likely human exposures via dermal penetration, while bolus and constant-rate infusion administrations were contrasted to mimic potential occupational exposure scenarios. The pharmacokinetic profiles of 2 methoxyacetic acid (2-MAA), the proximate toxic metabolite of 2-ME, were quantitated, generating peak concentration (Cmax) and total 2-MAA exposure values (24-hr area under the concentration-time curve; AUC) in the maternal plasma, extraembryonic fluid, and embryo. The total 2-ME dose (mg/kg) required to achieve similar 2-MAA levels (Cmax or AUC) in these compartments was 2- to 3-fold higher by constant-rate infusion than by bolus injection; therefore, no simple association existed between 2-MAA levels and the total 2-ME dose, when the dose rate was not considered. Similarly, there was no good correlation between the combined total 2-ME doses and the fetal malformation rate, although clear dose response patterns for paw malformations were observed in litters and fetuses for each individual dosing regimen. However, the combined 2-MAA pharmacokinetic data from each of the dosing regimens demonstrated that during the phase of maximum susceptibility of paw morphogenesis to disruption by 2-MAA (from gd 11 to gd 11.5), a strong linear correlation existed between fetal malformation incidence and 2-MAA AUC levels in either maternal plasma or embryonic compartments (linear correlation coefficient, r2 0.91-0.92). The correlation with Cmax was less favorable (r2 0.74-0.81) over the dose range studied. In a further experiment designed to investigate the importance of AUC vs Cmax regarding 2-ME teratogenicity, infusion of 2-ME (34.7 mg/kg/hr for 8 hr) beginning 2.5 hr after bolus loading (175 mg/kg) provided an increased 24-hr 2-MAA AUC without increased Cmax. This resulted in greater than 70% of the fetuses having various digit malformations (micro-, syn-, ectro-, and polydactyly), compared to only 32-35% of fetuses with mostly stunted digits when either dose was applied singularly. These data support total 2-MAA exposure (AUC levels), rather than peak 2-MAA concentrations, as the principle determinant of teratogenesis following exposure to 2-ME.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1585376 TI - Effect of lipoic acid on biliary excretion of glutathione and metals. AB - Several metals are excreted in bile as glutathione complexes, and their biliary excretion is facilitated by increased hepatobiliary transport of glutathione. The present study analyzed the effect of lipoic acid (LA; thioctic acid; 37.5-300 mumol/kg, iv), an endogenous disulfide which can be reduced in vivo to a dithiol, on the hepatobiliary disposition of glutathione-related thiols and the biliary excretion of metals (10 mumol/kg, iv) in rats. Administration of LA enhanced the biliary excretion of reduced glutathione in a dose-dependent fashion. Despite increasing glutathione output, LA (150 mumol/kg, iv) did not increase, but rather decreased, the biliary excretion of methylmercury, cadmium, zinc, and copper, which are transported into bile in a glutathione-dependent manner, as indicated by a marked reduction in their biliary excretion after diethyl maleate-induced glutathione depletion. In contrast, biliary excretion of inorganic mercury, which is minimally affected by glutathione depletion, was dramatically enhanced (12- to 37-fold) by LA administration. Following injection of LA, the concentrations of endogenous disulfides in arterial blood plasma (e.g., cystine, glutathione disulfide, cysteine-glutathione, protein-cysteine, and protein-glutathione mixed disulfides) were considerably diminished, while the levels of endogenous thiols (e.g., glutathione and cysteine) were increased. This finding indicates that LA, probably after enzymatic conversion to dihydrolipoic acid, can reduce endogenous disulfides to thiols. It appears that LA induces the transport of glutathione into bile by the temporary formation of dihydrolipoic acid-glutathione mixed disulfide, which after being translocated into bile is cleaved to LA and reduced glutathione. Because the glutathione molecule thus transported into bile cannot complex metals at the thiol group, this might be the mechanism for the observed failure of the LA-induced increase in biliary excretion of glutathione to enhance the hepatobiliary transport of metals that are transported into bile as glutathione complexes (i.e., methylmercury, cadmium, zinc, and copper). The observations also raise the possibility that endogenous dihydrolipoic acid, by forming a stable complex with mercuric ion, may play the role of a carrier molecule in the hepatobiliary transport of inorganic mercury. PMID- 1585377 TI - Fumonisin inhibition of de novo sphingolipid biosynthesis and cytotoxicity are correlated in LLC-PK1 cells. AB - Fumonisins are a group of structurally related compounds produced by Fusarium moniliforme. Recently, it has been shown that fumonisins B1 and B2 are the first naturally occurring inhibitors of sphingosine and sphinganine N-acyltransferase (ceramide synthase) in rat primary hepatocytes (Wang et al. J. Biol. Chem. 266, 14, 486-14, 490, 1991). These enzymes are key components in the pathways for de novo sphingolipid biosynthesis and sphingolipid turnover. The results of the present study show that fumonisins B1 and B2 inhibit proliferation and are cytotoxic to LLC-PK1 cells. Concentrations of fumonisin B1 and B2 between 10 and 35 microM inhibited cell proliferation, whereas higher concentrations (greater than 35 microM) killed cells. Inhibition of cell proliferation and cell death were preceded by a lag period of at least 24 hr during which cells appeared to be functioning normally. Cells exposed to fumonisin B1 exhibited normal growth kinetics and morphology soon after fumonisin B1 was removed; thus, the effects of fumonisin B1 were reversible. The EC50 for alterations in sphingolipid biosynthesis was 10 to 15 microM. Inhibition of de novo sphingolipid biosynthesis occurred before inhibition of cell proliferation or cytotoxicity, and the dose response for the decrease in the [3H]sphingosine to [3H]sphinganine ratio at 7 hr closely paralleled the dose response for effects on proliferation and cytotoxicity at 3-5 days. In addition, the level of free sphinganine, and to a lesser extent sphingosine, increased in fumonisin-treated cells in a dose dependent manner. During the 24-hr lag period preceding inhibition of cell proliferation, the free sphinganine content increased by 12,800% in cells exposed to 35 microM fumonisin B1. Whereas a mechanistic relationship between the inhibition of de novo sphingolipid biosynthesis and inhibition of proliferation and cell death has not been demonstrated, the results of this study support the hypothesis that inhibition of de novo sphingolipid biosynthesis is an early event in the toxicity of fumonisins to LLC-PK1 cells. PMID- 1585378 TI - In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p dioxin. 1. Effects on androgenic status. AB - When administered in overtly toxic doses to postpubescent rats, 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) produces a variety of adverse effects on the male reproductive system including a decrease in plasma androgen concentrations. If such an androgenic deficiency were produced prenatally and/or early postnatally it could potentially impair male reproductive function by disrupting the development of sex organs and/or causing incomplete sexual differentiation of the central nervous system. To determine whether TCDD can reduce androgen concentrations perinatally and/or impair androgen-dependent perinatal development, pregnant Holtzman rats were treated with 1.0 micrograms TCDD/kg or vehicle on Day 15 of gestation. Plasma testosterone concentrations in fetal males were significantly reduced by TCDD on Gestation Days 18 through 21. The surge in plasma testosterone concentrations shortly after birth was also significantly reduced, as was anogenital distance, an androgen-dependent parameter. To further investigate the effects of perinatal TCDD exposure on the male reproductive system, rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated from birth through sexual maturation. This report describes their growth, physical development, and androgenic status (i.e., androgen concentrations and androgen-dependent structures and functions); effects on spermatogenesis, testicular histology, sexual behavior, and fertility are reported separately. There was little evidence that TCDD caused maternal toxicity. Signs of overt toxicity in offspring were limited to an 8% reduction in live births (highest dose only) and to decreases in body weight gain and feed consumption (two highest doses only) which disappeared by early adulthood. With respect to androgenic status, maternal TCDD doses as low as 0.16 micrograms/kg produced significant dose-related decreases in the anogenital distance of 1- and 4-day-old males, delays in testicular descent, and decreases in seminal vesicle and ventral prostate weights. The reductions in organ weights were observed when rats were at the juvenile, pubertal, postpubertal, and mature stages of sexual development. Plasma testosterone and 5 alpha-dihydrotestosterone concentrations tended to be reduced at these times (though not significantly), while plasma luteinizing hormone concentrations were generally unaffected. Collectively, these results demonstrate that perinatal TCDD exposure alters the androgenic status of male rats from the fetal stage into adulthood, and that TCDD can affect androgenic status without causing overt toxicity. In rats, the male reproductive system appears to be more sensitive to the toxic effects of in utero and lactational TCDD exposure than any other organ or organ system studied thus far. PMID- 1585379 TI - Action of allopurinol and aspirin on rat whole-embryo cultures. AB - The effects of allopurinol (HPP) at concentrations ranging from 0.33-1.83 mM and of aspirin (ASA) from 0.28-2.22 mM, were studied on the rat whole-embryo culture system. Embryos were explanted at day 10 of gestation and cultured for 48 h, either in the absence or in the presence of rat and human S9. HPP proved to be potentially embryolethal and teratogenic without any S9, while it was embryolethal with rat S9 and dysmorphogenic with human S9. ASA showed an embryolethal and teratogenic potency without any S9 samples. These responses were increased in the presence of rat S9, while ASA embryolethality was predominant with human S9. These results obtained on rat embryos in culture suggest a correlation between the species origin of the biotransforming system and the known teratogenicity of HPP in sensitive animal models. However, ASA elicited responses not in agreement with the known teratogenic response in rodents. PMID- 1585380 TI - Effect of ethanol on the distribution of cadmium between the cadmium metallothionein- and non-metallothionein-bound cadmium pools in cadmium-exposed rats. AB - In an attempt to assess the effect of ethanol on cadmium accumulation, metallothionein (MT) synthesis, Cd-binding capacity and lipid peroxidation, rats were administered either Cd, ethanol or their combination for a period of 4 weeks. A significant increase in Cd accumulation was observed in all the organs of rats under study co-exposed to Cd and ethanol as compared to only Cd-treated rats. Increased MT levels in response to Cd were associated with a marked alteration in the distribution of Cd amongst the two pools of intracellular Cd i.e. Cd bound to MT (Cd-MT) and Cd not bound to MT (non-MT-Cd). Higher levels of non-MT-Cd were observed in liver, kidney and heart of Cd+ethanol-exposed rats as compared to only Cd-exposed rats. Lesser binding of 109Cd to the protein peak was observed in Cd+ethanol-exposed rats than the Cd-treated rats when hepatic supernatants from all the groups were chromatographed on Sephadex G-75 columns, suggesting that ethanol has a redistributing effect on Cd amongst the two pools. A marked increase in lipid peroxidation was observed which was linear to the increase in non-MT-Cd levels. A positive correlation between non-MT-Cd levels and lipid peroxidation was observed in liver, kidney and heart suggesting that non-MT Cd levels are more crucial and toxicologically more important than total Cd levels. PMID- 1585381 TI - Hematotoxic effects of benzene analyzed by mathematical modeling. AB - The hematopoietic cell response to benzene intoxication in mice (during and after long-term inhalation) was analyzed by a mathematical model of murine hematopoiesis. Two complementary methods, Time-Curve and Steady-State Analysis, were developed to identify target cells for benzene toxicity and to quantify the extent of damage in different stages of development of these target cells. We found that (i) erythropoietic cells were the most sensitive; (ii) granulopoietic cells were about half as sensitive as erythropoietic and (iii) hematopoietic stem cells exhibited a sensitivity that ranged between that of erythropoietic and granulopoietic cells. A dose-response relationship between benzene levels and damage in target cells (valid from 1 to more than 900 ppm) was derived that was linear for doses up to 300 ppm and plateaued thereafter. This relationship indicated that benzene-induced hematotoxicity is subject to a saturable process. Recovery of hematopoiesis following chronic benzene intoxication was simulated for different doses and preceding exposure periods. The impaired recovery following exposure periods greater than 8 weeks could be explained by a severe reduction in the maximum self-maintenance of stem cells. This study indicates that the present mathematical model represents a useful approach to investigate alternate hypotheses for the action of hematotoxic agents. PMID- 1585382 TI - Protective roles of metallothionein and glutathione in hepatotoxicity of cadmium. AB - The protective roles of metallothionein (MT) and glutathione (GSH) in acute hepatotoxicity of cadmium (Cd) were investigated in an in vitro system. Liver slices were incubated in a buffer containing cadmium chloride (20-50 ppm) at 37 degrees C for 3 h. Viability of the slices was monitored by measuring intra cellular potassium (K) content and GSH concentrations. A dose-dependent decrease of intracellular K content of GSH concentrations was observed. Pre-induction of MT (100-fold increase) by injection of zinc sulphate (30 mg Zn/kg body weight) showed protection against decrease in both intracellular K and GSH concentrations in liver slices. Decrease of hepatic GSH (90%) by an injection of buthionine sulfoximine (BSO)(4 mmol/kg body weight) to the rats further enhanced the Cd toxicity in the liver slices. This enhanced toxicity resulting from BSO treatment can be totally overvome by induction of MT by Zn pre-treatment. The cellular uptake of Cd remained unaltered in all experiments. These results demonstrate that hepatic toxicity of Cd may be due to its binding to intracellular sulfhydryl groups and both intracellular GSH and MT levels may provide protection against cytotoxicity of Cd in liver. Moreover, even at low GSH levels, MT could partially protect the hepatic cells from Cd cytotoxicity. PMID- 1585383 TI - Sub-acute toxicity of piperonyl butoxide in F344 rats. AB - Piperonyl butoxide, alpha-[2-(2-Butoxyethoxy)ethoxy]-4,5-methylenedioxy- 2 propyltoluene, is a pesticide synergist. F344 rats of both sex were maintained on diets containing 0, 0.6, 1.2 or 2.4% of piperonyl butoxide for 13 weeks. At the end of experimental period, they were necropsied. Selected organs were weighted and serum was analyzed by clinical chemistry. In male and female rats of the 2.4% group, body weight gains were depressed, macroscopically, hepatomegaly was marked and liver weights were significantly higher than those of the control group. In male and female rats of all treated groups, relative kidney weights were significantly increased in a dose-dependent manner. Rats of the 2.4%-group had increased levels of albumin, cholesterol, urea nitrogen and gamma-glutamyl transpeptidase. Examination of livers of the male 2.4%-group by light microscopy showed enlarged hepatocytes with glassy cytoplasm and fatty deposition. On occasion, there was coagulative necrosis of a few hepatocytes in the periportal area and oval cell proliferation. The kidney of treated rats showed atrophy of epithelium in the proximal convoluted tubules. These results indicated that toxicity of piperonyl butoxide in rats was directed primarily to the liver and kidney. PMID- 1585384 TI - Acute effects of carboxyatractyloside and stevioside, inhibitors of mitochondrial ADP/ATP translocation, on renal function and ultrastructure in pentobarbital anesthetized dogs. AB - To assess the direct renal toxicity of carboxyatractyloside (CATR), it was administered in relatively low intravenous (i.v.) doses (6.5 and 13.0 mumol/kg) to pentobarbital-anesthetized dogs that were being mechanically ventilated in order to circumvent severe extrarenal effects, such as hypoxemia, that could contribute to its nephrotoxicity. Within 2 h post-CATR, site-specific renal damage was noted in S2 and S3 cells of the proximal tubules; characteristic lesions in both cell types included loss of brush border, condensation of mitochondria and proliferation of small vesicles. Other S2 cells exhibited intense staining and reduced cell height. In 3 of 14 CATR-treated dogs, extrarenal effects were of sufficient magnitude to induce cellular swelling and occlusion of tubular lumina in S3 and thick ascending limb segments. Stevioside (STEV), related to CATR in structure and actions on the mitochondrial ADP/ATP translocase, was totally devoid of acute extrarenal or direct renal effects during the 6-h period following intravenous administration of 2.5 times the higher dose of CATR. The ability of CATR to produce renal toxicity via its renal and extrarenal actions emphasizes the importance of minimizing the latter actions of any toxicant when attempting to ascertain the mechanism by which it adversely affects renal function and ultrastructure. PMID- 1585385 TI - Importance of hepatocyte culture conditions in dimethylnitrosamine-induced suppression of antibody response in the mixed cultures of murine hepatocytes and splenocytes. AB - The role of the hepatocyte culture media in dimethylnitrosamine (DMN)-induced suppression of antibody responses by splenocytes against sheep erythrocytes (SRBCs) was investigated using the mixed culture system of murine hepatocytes and murine splenocytes. It was observed that hormone-supplemented complete media was required for hepatocyte cultures to optimally activate DMN to its immunosuppressive form(s). In the absence of the hormone supplement, the concentration of DMN required to produce a 50% suppression (IC50) was increased by over 10-fold (i.e., compare the IC50 in complete media of less than 0.5 mM to the IC50 in basal media of almost 10.0 mM). In contrast, the activation of cyclophosphamide (cytoxan, CTX), which was used in these studies as a comparative control, was not affected by the absence of the hormone supplement. These results indicate that the observed effect on the activation of DMN was not due to a generalized loss of metabolic capability of hepatocytes cultured without hormones. To examine the role of drug metabolizing capabilities of hepatocytes in the differential activation of DMN, we compared phase I and phase II enzyme activities of hepatocytes cultured for 24 h in either basal media or hormone supplemented complete media. Our results indicated that there was a significant decrease of phase I monooxygenase activities of cultured hepatocytes when compared to freshly isolated hepatocytes. However, our results failed to show any difference in the activities of hepatocytes cultured in the two media. Most notably, there was no difference in the activity of either high- or low-affinity DMN demethylase, as measured by the generation of formaldehyde. We observed a similar profile with phase II conjugative capabilities, specifically sulfotransferase and glucuronyltransferase. These results indicate that the activation of DMN to its immunosuppressive form(s) can be modulated in the co culture system by culturing hepatocytes under different conditions. Because we failed to show any differences in the metabolic capabilities of hepatocytes cultured under the two media conditions, the results suggest that the modulation of immunosuppressive activity may not be related to a change in the generation of the immunosuppressive metabolite(s). PMID- 1585386 TI - Roles of active oxygen species in glomerular epithelial cell injury in vitro caused by puromycin aminonucleoside. AB - The mechanism of puromycin aminonucleoside (PAN)-induced nephrosis has not yet been well defined. In the present study, we examined the protective effect of active oxygen scavengers on the PAN-induced injury of cultured rat glomerular epithelial cells (GECs) and the generation of active oxygen species in PAN treated GECs. When exposed to PAN (greater than or equal to 25 micrograms/ml), cellular damage occurred in a time- and dose-dependent manner as evaluated by both the LDH release and MTT colorimetric assays. Concomitant addition of either the hydrogen peroxide (H2O2) scavenger, catalase, or the iron chelating agent, deferoxamine, to the culture medium caused a striking reduction of cellular injury. This suggested a role for H2O2 and for hydroxyl radicals (OH.) generated via the iron-catalyzed breakdown of H2O2 in PAN nephrosis. Using the scopoletin fluorescence assay, the release of H2O2 into the culture medium by GECs exposed to PAN (greater than or equal to 50 micrograms/ml) was shown to increase dose dependently (greater than or equal to 57 +/- 11 pmol/4.4 x 10(6) cells per h, P less than 0.01) as compared with control cells (14 +/- 2 pmol/4.4 x 10(6) cells per h). These results strongly suggested that active oxygen species, especially H2O2 and OH., might play an important role in PAN-induced GEC injury in vitro as well as in vivo. PMID- 1585387 TI - Involvement of glutathione in cis-platinum toxicity in Escherichia coli K12. AB - Among the various biochemical functions assumed by the tripeptide glutathione (GSH), a role in cell protection against xenobiotics has been well established. In the case of resistance to cis-diamminedichloroplatinum(II) (CDDP) this role is controversial. CDDP reacts with nucleophiles and binds covalently to DNA, its ultimate target. We addressed the question of a putative role of GSH as a secondary non-essential target by using a bacterial model. With an Escherichia coli K12 mutant devoid of GSH, we found sensitivity to CDDP increased by a factor of two. It appeared that GSH protects bacteria at least by covalently trapping platinum before its binding to DNA since (i) lower binding of CDDP to DNA was found when GSH was present and (ii) the resistance still persisted in bacteria after treatment by the monofunctional derivative [Pt(dien)Cl]Cl. On the other hand, with a DNA repair defective mutant (lexA3), we found that other biochemical secondary target(s) might be involved in bacterial protection at low CDDP concentrations. PMID- 1585388 TI - Preparation of multiply deuterium-labeled cortisol. AB - Cortisol labeled with four deuterium atoms at chemically stable sites ([9,11,12,12-(2)H4]cortisol, cortisol-d4) was prepared by hydrogen-deuterium exchange and reductive deuteration reactions. After protecting the C-17 dihydroxyacetone side chain of cortisone (cortisone-BMD), hydrogen-deuterium exchange was carried out with 6.5% NaOD in MeOD, which was followed by protection of the C-3 carbonyl as the semicarbazone. Subsequent reductive deuteration at C 11 with NaBD4 followed by removal of exchangeable deuterium under the same exchange-reaction conditions in a medium of 6.5% NaOH in MeOH and deprotection afforded the desired cortisol-d4 with high isotopic content (d3, 21.2%; d4, 78.1%; d5, 0.74%). The method was applied to the synthesis of cortisol labeled with nine deuterium atoms [( 1,1,9,11,12,12,19,19,19-(2)H9]cortisol, cortisol-d9) starting from [1,1,19,19,19-(2)H5]cortisone (cortisone-d5). PMID- 1585389 TI - Effect of 5 alpha-dihydrotestosterone and dexamethasone on estrogen receptors of the anterior pituitary and uterus. AB - The administration of 5 alpha-dihydrotestosterone (5 alpha-DHT) and dexamethasone has been shown to attenuate estrogen-induced prolactin release in the estrogen primed rat. Therefore, the effect of these compounds was studied on anterior pituitary and uterine estrogen receptors. Injection of 0.8 mg/kg body weight of 5 alpha-DHT to ovariectomized adult rats treated with 2 micrograms estradiol/d for 4 days resulted in a significant decrease in occupied nuclear estrogen receptors of the anterior pituitary but not the uterus. Estrogen priming was essential for 5 alpha-DHT effect on occupied nuclear anterior pituitary estrogen receptors because this effect did not occur in ovariectomized vehicle-treated control animals. The administration of 1 mg/kg body weight of dexamethasone brought about a decrease in uterine but not anterior pituitary nuclear estradiol receptors. These results provide further evidence that the regulation of estrogen receptor dynamics is different in the anterior pituitary and the uterus and that different steroids can exert tissue-specific effects. PMID- 1585390 TI - Preparation of the N-(4'-hydroxy-[3'-125I]iodophenethyl)-6-(4-O diethylstilbestryl)hexanam ide for diethylstilbestrol radioimmunoassays. AB - The synthesis of a radioiodinated diethylstilbestrol (DES) derivative is described. This derivative was prepared by coupling the previously synthesized active ester of 6-(4-O-diethylstilbestryl)hexanoic acid with mono [125I]iodotyramine in dry tetrahydrofuran (20 to 22 C, 16 hours). The mono [125I]iodotyramine was prepared using a chloramine-T method and purified by paper electrophoresis. The final product, N-(4'-hydroxy-[3'-125I]iodophenethyl)-6-(4-O- diethylstilbestryl)hexanamide, was separated by thin-layer chromatography (cyclohexane/ethanol/NH4OH 2.5 N/acetone; 40:50:5:20, v/v/v/v); it was stable for 2 months in ethanol at 4 C and had a specific activity higher than 540 Ci/mmol. The [125I]DES amide synthesized was found to retain the immunoreactivity of DES, since it competed with [3H]DES or DES in an in vitro radioimmunoassay system for the binding sites of a rabbit anti-DES antibody; thus, it seems to be capable of replacing the tritiated tracer used so far in DES radioimmunoassays. PMID- 1585391 TI - Radioimmunoassay of 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol 3 glucuronide in serum of patients with cerebrotendinous xanthomatosis. AB - A rapid, convenient, and specific radioimmunoassay for 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol has been developed. Specific antiserum was obtained from rabbits immunized by the bile alcohol-bovine serum albumin conjugate, which was coupled by an (O-carboxymethyl)oxime bridge at the C-3 position. The assay produces values for serum concentrations of bile alcohol glucuronides in patients with cerebrotendinous xanthomatosis. PMID- 1585392 TI - Exposure to ovarian steroids elicits a female pattern of plasma cortisol levels in castrated male macaques. AB - Our recent observations (1) that there is a difference in circadian patterns of plasma cortisol levels between male and female macaques and (2) that after gonadectomy these differences in the patterns and in the levels of cortisol were reduced prompted us to investigate how 17 beta-estradiol (E2) and progesterone affect cortisol secretion in orchidectomized male rhesus macaques. Five male macaques, castrated as adults, were implanted subcutaneously with segments of silastic tubing filled with E2 and with progesterone in a manner such that the levels and the sequence of these hormones mimicked those that occur during the menstrual cycle of intact female macaques. Since previous studies had shown that the difference in cortisol patterns was due to higher levels in females during the day, these studies were conducted from 0800 to 2000 hours. Blood samples were collected in an adjacent room at 15-minute intervals. Separate trials were conducted 2 weeks after E2 was implanted and levels were 110 +/- 14 pg/ml and again 2 weeks later after progesterone was implanted and E2 levels were 59 +/- 15 pg/ml; progesterone levels averaged 4.0 +/- 0.65 ng/ml. Mean plasma concentrations of cortisol (microgram/100 ml) for the 12-hour period were three fold higher in orchidectomized males treated with E2 (17.2) and with E2 + progesterone (18.0) than in intact males (4.9). Levels in males treated with ovarian steroids were double that (8.5 micrograms/100 ml) observed for intact females.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585393 TI - Pharmacokinetic population parameters for aminoglycosides in cholecystitis patients. AB - We report the use of a new method to determine patient population pharmacokinetic parameters (nonparametric expected maximum or NPEM). Our purpose was to develop and then analyze the utility of these parameters, compared to a more traditional approach. Nineteen patients with acute cholecystitis made up the control group for defining the parameters via NPEM. The standard of practice was to use a model created from a different intraabdominal infection group (appendicitis), referred to as "surgical patient model." These two models were compared with a group of 23 patients receiving gentamicin for acute cholecystitis. We concluded that the NPEM model was superior to the surgical patient model in predicting gentamicin trough and peak levels with less bias and better precision. PMID- 1585394 TI - Steady-state pharmacokinetics and bioavailability of total and unbound disopyramide in children with cardiac arrhythmias. AB - We studied the pharmacokinetics of the total (protein-bound plus -unbound and unbound forms of disopyramide (DP) at steady-state in six children (aged 5.2 to 12.2 years) with cardiac arrhythmias who had received repeated oral DP therapy. Maximum concentrations after the oral dose were reached at 2.5 +/- 1.1 h (mean +/ SD) for both total and unbound DP. The bioavailabilities calculated from total and unbound plasma concentration-time curves were 99 +/- 23 and 89 +/- 27% of the dose, respectively. These parameters seen in our children are similar to those reported from adult subjects. The mean elimination half-lives (t1/2), volumes of distribution, and total body clearances (CL) of total and unbound DP were 3.15 +/ 0.64 and 2.50 +/- 0.37 h, 1.02 +/- 0.25 and 2.60 +/- 0.38 L/kg, and 3.79 +/- 0.82 and 13.12 +/- 2.60 ml/min/kg, respectively. These mean CL and t1/2 values are considerably greater and shorter, respectively, than those reported from adult subjects. The findings indicate that the greater doses of DP per kg of body weight reportedly required for attaining a therapeutic plasma drug level in pediatric age patients should be due to a greater drug CL in children than in adults. A sustained-release preparation of DP may be required for pediatric patients to minimize a large fluctuation of plasma drug levels during the dosing intervals. PMID- 1585395 TI - Persistent impairment of clomipramine demethylation in recently detoxified alcoholic patients. AB - The purpose of the present study was to investigate whether the metabolism of clomipramine is altered by chronic alcohol drinking. Eleven recently detoxified alcoholic patients were included (experimental group EG) and compared to a reference group of patients with no history of alcoholism (reference group RG, n = 102). Blood concentrations of clomipramine and its metabolites were measured as part of the routine drug monitoring program. Clearances were estimated from trough concentrations, according to a model developed previously. Results indicate strong inhibition of demethylation clearance in group EG, when compared to group RG (median values 9.9 and 24.2 L/h), with significant increase of the clomipramine to desmethylclomipramine ratio (median values 1.00 and 0.36). No difference was found for hydroxylation. In addition, high correlation is observed between hydroxylation and demethylation clearances in group EG (Spearman rs = 0.82), but not in reference group RG (rs = 0.29). Follow-up data indicate that impairment of demethylation capacity can persist for several weeks or months after withdrawal from alcohol. The interest of calculating clomipramine to desmethylclomipramine ratios during routine drug monitoring is emphasized, values of 1 or larger often being associated with liver disease and/or alcohol-related problems. PMID- 1585396 TI - Individualized dosage of gentamicin: a programmed pocket calculator is useful only when applied properly. AB - Various methods of gentamicin dosing were compared in order to evaluate factors that prevent achievement of therapeutic peak and trough plasma concentrations in every patient. When standard doses of 3 x 80 mg of gentamicin/day (i.e., 3 x 170 mumol/day) were administered, only 26% of peak and 51% of trough plasma concentrations were within the desired range. This percentage increased for peak levels to 54% (p less than 0.001) when physicians were instructed in the use of a programmed pocket calculator (PPC) and to 70% (p less than 0.001) when in addition the nursing staff was trained. The best results were achieved when dosing and blood sampling were supervised by a single trained person, 76% of initial peak and 71% of initial trough levels being within the therapeutic range. In this group of patients, further dosage adjustments by the PPC achieved 92% of peak levels in the desired range, while no patient had elevated trough levels. Analysis of the factors that led to these results revealed that neither the laboratory nor the PPC are limiting factors for optimal results. The goal of therapeutic plasma concentrations can be achieved, but requires appropriate attention to the accuracy of blood sampling and dosing. For this purpose, a special program, i.e., more than ordinary attention to drug therapy, is needed. PMID- 1585397 TI - Comparative absorption of atropine from a metered-dose inhaler and an intramuscular injection. AB - The inhalation of atropine sulfate from a pressurized metered-dose inhaler was investigated in a nonrandomized four-period rising-dose study. Eight healthy, nonsmoking subjects received 1.7, 3.4, and 5.2 mg of atropine sulfate by inhalation and 1.67 mg of atropine free base (equivalent to 2 mg of atropine sulfate) by intramuscular (i.m.) injection. Serum atropine sulfate concentrations were measured over a 24-h period by gas chromatography/mass spectrometry. Mean serum concentrations increased nonproportionally as the inhaled dose increased. Mean peak concentrations were 4.9, 6.1, and 7.9 ng/ml for the inhaled doses and 8.4 ng/ml for the i.m. dose. Typical anticholinergic effects were seen after all doses. PMID- 1585398 TI - Theophylline concentrations in serum, saliva, and cerebrospinal fluid in patients with essential tremor. AB - Theophylline concentrations in saliva and serum were compared in 20 patients with essential tremor. There was a strong correlation between the concentrations in saliva and serum (r = 0.9, slope of 0.48). The ratio between unbound and bound theophylline as assessed by ultrafiltration was 0.30. This ratio was similar to that between theophylline concentrations in CSF and serum. The theophylline concentration in serum was not predictable from that obtained in saliva in individual cases. Moreover, the levels in saliva were about 20% higher than the unbound concentrations of theophylline in serum. PMID- 1585399 TI - Measurement of rapamycin in whole blood using reverse-phase high-performance liquid chromatography. AB - Rapamycin (RAPA) is an immunosuppressant with a potency similar to FK 506 and up to 100-fold greater than cyclosporine. To date, no data have been reported on the pharmacokinetics and disposition of the drug, primarily due to a lack of suitable methods for its analysis. We describe here an evaluation of a reverse-phase high performance liquid chromatographic (HPLC) method for analysis of the drug in whole blood. The method showed excellent analytical recovery of the drug, close to 100%. The sensitivity method was found to be 1.0 micrograms/L with between-run coefficients of variation of 14.4% and 9.8% at 10 and 50 mg/L. The stability of RAPA was investigated with this method in whole-blood specimens. It was found that the drug was stable for 30 days at 4 degrees C and for 55 days at -40 degrees C. PMID- 1585400 TI - Comparison of a new high-performance liquid chromatography method with fluorescence polarization immunoassay for analysis of methotrexate. AB - A simple high-performance liquid chromatography (HPLC) method for the determination of methotrexate (MTX) in biological fluids is described. The assay is rapid, the time required for analysis is less than 30 min, and it is sensitive, up to 0.01 microgram/ml, which is three times below the toxic MTX concentration. Fifty plasma samples drawn from acute lymphocytic leukemia (ALL) patients were used to compare this method with that of fluorescence polarization immunoassay (FPIA). A good correlation (r = 0.979) was obtained between the results of the two analyses. FPIA constantly overestimates the concentration in samples collected during elimination and underestimates those collected during infusion. The difference between the means of the two methods was 29% and 13% for the elimination and infusion samples, respectively. The means of the peak height ratio of the metabolite to MTX in the HPLC chromatograms were 3.39 and 0.33 during elimination and infusion, respectively. The results therefore indicate that HPLC is more specific when tracing the washout of MTX concentration. Because of this specificity and simplicity, the method is recommended for therapeutic drug monitoring. The stability of MTX in human saliva was investigated in this study. MTX was found to be stable at room temperature and at -20 degrees C for a minimum of 3 h and 3 weeks, respectively. PMID- 1585401 TI - Determination of free serum digoxin concentrations in digoxin toxic patients after administration of digoxin fab antibodies. AB - Digoxin fab antibody therapy is known to interfere with digoxin immunoassays causing spurious serum digoxin concentrations. The reliability and precision of three digoxin immunoassays--Baxter Dade Stratus (BDS), Syva affinity column enzyme-mediated immunoassay (EMIT), and the reference assay Abbott TDx fluorescence polarization immunoassay following ultrafiltration (FPIA-UF)--were compared in eight digoxin toxic patients treated with digoxin fab antibodies. Five to eight blood samples were drawn serially up to 204 h post digoxin fab therapy. The serum digoxin concentration in each sample was determined by each of the three assays. The mean (+/- SD) area under the serum digoxin concentration time curve was significantly lower for FPIA-UF than for BDS or EMIT (86.1 +/- 58.2 vs 158.1 +/- 88.6 and 176.3 +/- 115.3 h.ng/ml p less than 0.01, respectively). BDS correlated better with FPIA-UF (r2 = 0.71) than did EMIT (r2 = 0.45). Predictive performance of the BDS and EMIT assays demonstrated that the mean prediction error (bias) (0.62 vs 0.78 ng/ml) and the mean squared prediction error (precision) (0.48 vs 0.76) differed significantly from zero (p less than 0.05). However, BDS had significantly less bias and greater precision than did EMIT (p less than 0.05). In the presence of digoxin fab antibodies, BDS is a better predictor of free serum digoxin concentration than is EMIT, but both have considerable bias. Based on these results, FPIA-UF should be the assay of choice for determining free serum digoxin concentrations during fab therapy. PMID- 1585402 TI - Audit exposes flawed blood sampling for "digoxin levels". AB - Therapeutic "digoxin level" monitoring in selected wards was audited. Time elapsing between the last dose and blood sampling was considered appropriate if greater than or equal to 6 h. If such details were not entered on the requisition, the maximum time elapsing was estimated as "appropriate" or "inappropriate" from the time samples were logged into the laboratory and the time the last dose was entered in the patient's treatment sheet. In 22 requisitions detailing sampling time, nine were considered inappropriate. In an additional 150 instances, timing was estimated as inappropriate in 45. Among the 118 requests where timing (estimated or labelled) was appropriate, available plasma digoxin concentrations yielded a mean of 1.0 nM, compared to 1.6 nM in the corresponding 54 patients with premature sampling; this difference was both clinically and statistically significant (95% confidence limits 0.8-1.2 and 1.3 1.9 nM, respectively, p less than 0.001). Premature blood sampling for digoxin levels was common and associated with higher concentrations than when appropriate. Such inappropriate timing may not have serious consequences, but digoxin levels are a matter of record and are used for teaching; due attention to timing could provide more reliable information and avoid wasting valuable resources. PMID- 1585403 TI - A micro-enzyme-multiplied immunoassay technique plate assay for antiepileptic drugs. AB - Underutilization of antiepileptic drug monitoring in research situations has made comparison of data difficult to interpret. Experimental animal studies of the effects of antiepileptic drugs are similarly hindered by the lack of methods utilizing small blood samples to determine drug levels. To alleviate both problems, a standard enzyme-multiplied immunoassay technique (EMIT) assay was modified and scaled down. The resulting microEMIT utilizes only a fraction of the costly reagents (5.0 vs. 50.0 microliters) of the original assay and requires only 3-5 microliters of serum, easily obtainable from experimental animals. The method has been successfully tested with three major antiepileptic drugs, phenytoin (PHT), valproic acid (VPA) and carbamazepine (CBZ). The microEMIT assay, utilizing a 96-well plate, displays linear kinetics in the production of reduced nicotinamide adenine dinucleotide (NADH) for at least 8 minutes. The assay is linear from 2 to 100 micrograms PHT/ml, from 2 to 50 micrograms CBZ/ml and from 10 to 150 micrograms VPA/ml. The similarities suggest that a general adaptation for most EMIT drug assays will be possible. PMID- 1585404 TI - Development of a radioreceptor assay to measure glucocorticoids. AB - We have developed a radioreceptor assay to measure glucocorticoids. The assay employs the partially purified 95-kDa receptor isolated from human liver and purified by size fractionation on high-performance liquid chromatography (HPLC). In the assay [3H]prednisolone competes with steroids (endogenous and exogenous) for binding to the receptor. Bound and free are separated by treatment with charcoal. The between-day precision [% coefficient of variation (CV)] at concentrations of 9.4, 18.7, and 69.9 micrograms/L prednisolone is 16.6, 9.3 and 4.5%, respectively. Specificity studies revealed that hydrocortisone, deoxycorticosterone, 4-pregnene-17 alpha,21-diol-3,20-dione, 17 alpha hydroxyprogesterone, corticosterone and beta-hydroxyprogesterone all compete with [3H]prednisolone for binding to the receptor. Prednisone and 6 alpha-methyl prednisolone displace [3H]prednisolone to only a minor degree. The assay has been used to assess "glucocorticoid activity" in children with rheumatic diseases treated with prednisolone. PMID- 1585405 TI - Use of a radioreceptor assay in the assessment of cushingoid features in patients with juvenile rheumatic diseases. AB - A marked variation has been observed in severity of cushingoid appearance in patients with rheumatic diseases (RD) following steroid administration. We studied ten children with RD to determine if a relationship exists between cushingoid features and an individual's steroid activity as measured by prednisolone equivalents using a radioreceptor assay. Cushingoid features were clinically assessed by a "cushing score" according to the method of Bergrem. Patients were assigned to either the cushingoid (C) or noncushingoid (NC) group at study entry according to their cushing score. Blood was drawn prior to prednisone ingestion and then at 30, 60, 90, 120, 240, and 360 minutes and each sample was assessed for prednisolone equivalents and also for free and total cortisol. Group comparisons of dose-adjusted area under curve (AUC) and peak response are reported. Cushingoid patients had higher plasma prednisolone equivalents (PE) than noncushingoid patients as measured by peak PE and AUC. The PE.6 h/L average AUC for C patients was 248 micrograms PE.6 h/L versus 134 micrograms PE.6 h/L for NC patients. This nearly twofold difference was also noted between mean peak values (C 82 micrograms/L vs. NC 44 micrograms/L). Spearman correlations of Cushing scores with these two parameters indicated significant (p less than 0.05) relationships. A patient's Cushing score correlated best with peak response (rs = 0.78) and also with AUC (rs = 0.72). Measurement of plasma peak PE or AUC could be valuable for individualizing steroid dosing in children with RD. PMID- 1585406 TI - Clinical drug toxicology. PMID- 1585407 TI - Effect of food on salsalate absorption. AB - To assess the effect of food on salsalate absorption, single 1500-mg oral doses of salsalate were administered to 17 men under fasted and fed conditions according to a randomized open-label crossover design. A 7-day washout separated treatment periods. Blood samples were drawn throughout the 48-h period following dose administration and the resulting plasma samples assayed by high-performance liquid chromatography (HPLC) for unchanged drug, salsalate, and the major metabolite, salicylic acid. When results for the fasted and fed treatments were compared, no significant differences were observed in the pharmacokinetic parameters for the major metabolite salicylic acid or in the extent of absorption of unchanged drug; however, the rate of salsalate absorption was affected. Although the time-to-peak for salsalate was significantly delayed by approximately 1 h in the presence of food, the peak level was not significantly affected. The lack of difference between the two treatments for the therapeutic moiety, salicylic acid, indicates a lack of a significant food effect on single doses of salsalate. PMID- 1585408 TI - Haloperidol disposition is dependent on debrisoquine hydroxylation phenotype. AB - To investigate the importance of genetic factors for the regulation of haloperidol metabolism, we studied the disposition of a single oral dose of this drug in a panel of six extensive (EM) and six poor (PM) metabolizers of debrisoquine. PM eliminated haloperidol significantly slower than EM, the plasma half-life being longer (mean 29.4 +/- S.D. 4.2 and 16.3 +/- 6.4 h; p less than 0.01) and the clearance lower (1.16 +/- 0.36 and 2.49 +/- 1.31 L/h/kg; p less than 0.05). A 4-mg dose of haloperidol was given to the first three PM, but all three developed side effects, and a 2-mg dose had to be given to the next three PM subjects. All EM received 4 mg haloperidol. The disposition of haloperidol is thus associated with the genetically determined capacity to hydroxylate debrisoquine. PM of debrisoquine (7% of Caucasian populations) might, therefore, on common doses of haloperidol, achieve high plasma concentrations and thereby have an increased risk of side effects. At the other extreme, very rapid metabolizers may need increased doses of haloperidol. PMID- 1585409 TI - Performance of techniques for measurement of therapeutic drugs in serum. A comparison based on external quality assessment data. AB - Ten assay techniques were compared using measurements of a range of 15 drugs spiked in freeze-dried samples of serum reported to the Heathcontrol External Quality Assessment Scheme between November 1988 and January 1991. Three measures of performance were studied: frequency of outliers greater than 3 standard deviations from the sample mean, the coefficient of variation (CV) of sample measurements, and the difference of the sample mean from the spike value. The most consistently precise technique was polarisation fluoroimmunoassay (PFIA). It was in the group of techniques producing significantly fewer outliers and lower CVs than other techniques for all its target analytes. However, a specific interaction with the animal serum used as sample matrix resulted in significant negative bias in PFIA measurements of carbamazepine. Other immunoassay techniques and high-performance liquid chromatography also performed well for a range of analytes, in most cases giving less than 6% of outliers with CVs of less than 13% and less than 5% bias. The least satisfactory techniques were nephelometry and gas-liquid chromatography with derivatisation, which for several analytes gave significantly more outliers and higher CV values than other techniques. In samples containing carbamazepine-10, 11-epoxide, immunoassay measurements of carbamazepine showed cross-reactivity with the epoxide metabolite of between 7 and 15%. PMID- 1585410 TI - Image analysis of lymphoid cell differentiation in rat thymus throughout development. AB - In order to identify subtle changes in cell morphology and nuclear pattern modification during thymus ontogenesis, cell image analysis using System for Analytical Microscopy in Biological Applications (SAMBA 200) was applied in 9 stages of rat thymus development. The morphometric and chromatin parameters made it possible not only to identify automatically between the two main cell populations in the thymus gland (lymphoid and epithelial cells), but also to classify automatically 5 lymphoid sub-populations (lymphoid stem cells, lymphoblasts, large lymphocytes, medium lymphocytes and small lymphocytes). The evaluation of the 18 parameters during the lymphoid cell differentiation was studied in detail. The nuclear texture parameters made it possible to discriminate, in each cell subpopulation, 4 phases of cell cycle (G0, G1, S phase, and cells in G2). Evaluation of the nuclear parameters of the cell cycle in each lymphoid sub-population was studied in this investigation. The results illustrate the high majority of the lymphoid stem cells at the 14-day-old embryo stage while in the 20-day-old embryo the small lymphocytes become the main part of the whole lymphoid population. From the continuously renewed modification of lymphoid nuclear image analysis we discuss the origin of thymus lymphocytes. Lymphoid cells can be distinguished into different functional states and the striking morphological changes appearing during cell differentiation are related with drastic structural changes occurring in chromatin pattern from undifferentiated lymphoid stem cells to small lymphocytes. Terminal cell differentiation is associated with inhibited cell proliferation. The relative increase of chromatin condensation and nuclear pattern heterogeneity which reaches an extreme in small lymphocytes is accompanied by a progressive diminution of the nuclear area during the successive differentiation of the lymphoid population. Using one parameter of the nuclear texture features from the co-occurrence matrix (as LM or CON) and one parameter of the nuclear textures from the run-length section matrix (as GLD or RPC) the image analysis can discriminate between the different states of lymphoid cell differentiation. PMID- 1585411 TI - T-cell colony formation from murine thymocyte subpopulations and pre-T cells. AB - Murine thymocytes are able to proliferate on clonal basis as colonies in the semisolid medium methylcellulose. It has previously been shown that the colony forming cells are predominantly rather mature thymocytes and presumably exclusively single positive CD8+ cells. The results of the present study point to that also immature CD4-CD8- (DN = double negative) thymocytes and pre-T cells from nude mice are able to form colonies in methylcellulose culture. The numbers of colonies are increased by the presence of phorbolester, and it is shown by the addition of various interleukins to the culture that IL-2 is the essential interleukin in colony formation. It is further shown that all colony cells derived from DN thymocytes are of the CD4-CD8+ phenotype, while nude mouse precursors give rise to either CD8+ or DN colony cells. Thus, no CD4+ T cells were able to proliferate as colonies by the present culture method, even after exposure to a number of different interleukins or phorbolesters. This makes the method a reliable tool for clonal growth of both immature and mature CD8+ thymocytes and T cells. PMID- 1585412 TI - Evidence for elevated prothymocyte activity in the bone marrow of New Zealand Black (NZB) mice. Elevated prothymocyte activity in NZB mice. AB - New Zealand Black (NZB) mice spontaneously develop an autoimmune syndrome similar to that of systemic lupus erythematosus. Numerous abnormalities in T lymphocyte development have been reported in NZB mice, and the autoimmune syndrome can be adoptively transferred to naive recipients using bone marrow cells. In the present study, we have used an adoptive transfer system to study quantitatively the relative prothymocyte activity of marrow in either young (4-6 weeks of age) or older (8-10 months of age) NZB mice. Our results demonstrate that NZB marrow has approximately 7-fold more prothymocyte activity than that of marrow in SEA mice, a histocompatible, non-autoimmune prone normal strain of mice. This was ascertained by a competitive repopulation assay, in which mixtures of NZB and SEA prothymocytes were compared directly for their ability to repopulate the thymus of adoptive recipients. This increase in prothymocyte activity in the primary recipient of NZB marrow was associated with an increased competitive advantage of NZB marrow prothymocytes over that of SEA marrow prothymocytes in repopulating the hemopoietic (bone marrow) compartment of the primary host. These findings suggest that elevated prothymocyte activity in NZB mice, along with our previously presented evidence for abnormalities of thymocytopoiesis in NZB mice, may be important in their predisposition for autoimmunity. PMID- 1585413 TI - Ultrastructural localization of Terminal deoxynucleotidyl Transferase (TdT) in rat thymocytes. AB - TdT positive cells in rat thymus belong to distinct subsets as shown by light and electron microscopic immunocytochemistry. Using polyclonal antibodies to calf TdT and peroxidase labeled goat anti-rabbit IgG it has been possible to identify several subpopulations of TdT positive thymocytes. Large blasts corresponding to thymocytes at early maturational stages, are strongly positive for TdT which is diffusely distributed in both the nucleus and the cytoplasm. Smaller cells which correspond presumably to more advanced stages of maturation display nuclear TdT only, or are negative. Ultrastructural analyses of TdT indicate that the localization of the enzyme is related to the morphological features of the cells and TdT expression corresponds to maturational stages of T-cells. PMID- 1585414 TI - Immunopharmacology of ST 789. PMID- 1585415 TI - ST789: a new synthetic immunomodulator. AB - ST 789 is a synthetic compound which belongs to a new family of hypoxanthine derivatives exhibiting an aminoacidic function at the N-9 position of the purine ring. Available literature indicates that hypoxanthine derivatives exhibit well established immunomodulant properties. Furthermore, the addition of arginine to these molecules proved able to strongly enhance their immunomodulant activity. We review here the immunomodulant properties of both arginine and arginine containing compounds, and mostly of ST 789. PMID- 1585417 TI - Arginine-containing compounds and thymic endocrine activity. AB - The frequent association of malnutrition, infectious disease and aging has stressed the role played by some nutrients on the immune efficiency and particularly on the age-dependent immunological decline. Since arginine has been proven to enhance immune efficiency as demonstrated by the observation that supplemental dietary arginine accelerates would healing and increases thymus weight, we have evaluated the influence of oral administration of arginine on the age-associated immune deficiencies and in particular on the reduced thymic endocrine activity, as measured by the circulating level of one of the best known thymic peptides, i.e. thymulin. Thirty days oral treatment with arginine at the dose of 0.03 g/Kg b.w./day in 20 month old mice induces a full recovery of thymic endocrine activity and a significant increase of PHA responsiveness by spleen cells, when compared with untreated age-matched controls. In humans, oral administration of a commercially available arginine-lysin combination (Lysargin, Baldacci, Pisa, Italia) at the dose of 4 gr. of arg. + 4 gr. of Lysine induces a significant increment of thymulin blood level both in elderly and in cancer patients and at peripheral level, an increase of CD4+ lymphocyte subpopulation. These findings confirm the immunomodulation role of arginine and suggest that on the target of arginine as the thymus and particularly its endocrine activity. Furthermore arginine and arginine-containing compounds may offer a new therapeutical approach to restore thymic immunodeficiencies associated with age or secondary to pathologies inducing thymic deterioration such as trauma, stress and cancer. PMID- 1585416 TI - Enhancement of murine NK cell activity generation by ST 789. AB - We have evaluated the effect of in vivo administration of hypoxanthine derivative ST 789 on the reconstitution of natural killer (NK) cell activity of mice undergoing syngeneic bone marrow (BM) transplantation. Lethally irradiated BD2F1 mice were injected i.v. with 10(7) syngeneic BM cells and treated with ST 789 (50 mg/Kg ip) from day 1 through day 3 after BM graft. The splenic NK activity was evaluated at 7, 10, 14 and 17 days after irradiation and BM graft by the in vitro cytotoxicity assay against NK-sensitive YAC-1 target cells. Results indicate that treatment with ST 789 significantly enhances the NK activity reconstitution as compared to medium treated controls. These results suggest that ST 789 treatment is capable to induce the in vivo expansion of BM NK-progenitor cells resulting in a shorter time of regeneration of NK cell activity. PMID- 1585418 TI - ST 789 and ST 789 analogs: synthesis and analytical profile. AB - The procedure followed for the preparation of ST 789 and a series of origin derivatives analogs to ST 789 are described. A complete analytical profile of ST 789 and a concise profile of its analogs are also reported, together the purification methods applied. PMID- 1585419 TI - Pharmacokinetic investigation of ST 789 in rats and mice. AB - Pharmacokinetics of ST 789 were investigated in rats and mice after oral, intravenous, subcutaneous and intramuscular routes. A HPLC method validated for pharmacokinetic studies allowed the Authors to assay ST 789 concentration in plasma, urine and tissues. ST 789 interacted poorly with albumin and plasma proteins. Blood-to-plasma concentration ratio proved to range on average from 1.3 to 2.0 in both in vivo and in vitro studies. Plasma concentration-time behaviour after i.v. injection fitted according to the open three-compartment model; after subcutaneous and intramuscular routes two phases were observed and after oral route the absorption and one elimination phases were detected. Pharmacokinetics of ST 789 proved to vary linearly with the dose administered. Cumulative urinary excretion after parenteral administration ranged on average 60-80% and cumulative biliary excretion was 9.47% of the dose given. Oral administration allowed only 2.5% of the drug given to be excreted in urine, this leading to conclude that this drug is poorly absorbed through the intestine wall. After oral administration ST 789 produced relatively high concentration in lungs and lymphatic tissues, this leading to hypothesize a lymphatic component in its enteral absorption. PMID- 1585420 TI - Influence of ST 789 on murine thymocytes: a flow cytometry study of thymocyte subset distribution and of intracellular free Ca++ increase upon activation. Murine thymocytes and ST 789. AB - The coordinate expression of CD4 and CD8 antigens defines four major subsets of adult mouse thymocytes (CD4+CD8-, CD4+CD8+, CD4-CD8+ and CD4-CD8-) that represent definite steps in the differentiative pathway of immature T-lymphocytes. Thymocytes from adult C57BL/6 mice were cultured in the presence of ST 789, an L Arg synthetic derivative of hypoxanthine, (1 to 100 micrograms/ml) or PHA 60.1 to 1 microgram/ml), or both for 48 hours, and then stained with monoclonal antibodies to CD4 and CD8 antigens for dual color flow cytometry analysis. The expression of CD25, was also investigated. ST 789 was ineffective in modifying the distribution of the four thymocyte subsets and did not induce the appearance of CD25 on cortical thymocytes. PHA induced a dramatic dose-dependent decrease of the CD4+CD8+ subset that, however, was neither enhanced nor antagonized by ST 789. We also tested ST 789 for its ability to stimulate intracellular free Ca++ rise in thymocytes. The compound was ineffective in this assay. Conversely, thymocytes promptly responded to PHA stimulation. It is concluded that ST 789 has no effect on normal adult thymocyte differentiation/activation pathway. PMID- 1585421 TI - Influence of ST 789 on interleukin-1, interleukin-2 and interferon-gamma production from normal human peripheral blood mononuclear cells. AB - ST 789, previously named PCF 39, is a synthetic hypoxanthine derivative endowed with immunomodulating properties. However, the mode of action of this compound on immunocompetent cells has not yet been elucidated and, in particular, no evidence has been provided on its ability to trigger monokine (MK) and lymphokine (LK) release. In this framework, here we have evaluated the influence of ST 789 on interleukin (IL)-1, IL-2 and interferon (IFN)-gamma production from normal human peripheral blood mononuclear cells (PBMC). Results will show that following stimulation of PBMC with lipopolysaccharides (LPS) or lectins [phytohemagglutinin (PHA) and concanavalin A (Con A)] in the presence of increasing concentrations of ST 789 no modification of cytokine release is obtained, in comparison with cultures activated with LPS or lectins. In addition, this hypoxanthine is not able per se to induce release of MKs and LKs. The overall results suggest that ST 789 acts on the immune system through mechanisms which are not dependent on the release of ILs and IFN-gamma. PMID- 1585422 TI - Immunomodulators: current and future development and application. AB - It has been amply demonstrated that immunomodulators have a place in the armamentarium with other therapeutic modalities for the treatment of various diseases. They presently are, and in the future will be, most effective in preventing diseases which cause, or are the result of, immunodeficiencies. For future development the biological agents that are potent immunomodulators can be more purified and their molecular structures defined and synthesized, such as muramyldipeptides are products of BCG, etc. The active moiety of Picibanil (OK 432), a very powerful immunostimulator should be defined. Further investigations in isolating and characterizing biological agents as immunomodulators should continue in view of the success that has been achieved with BCG in treating superficial transitional cell bladder carcinoma. This mode of treatment is much less toxic to the patient than treatment with the cytotoxic agents thiotepa, mitomycin C. Chemically defined immunomodulators have been used successfully when combined with other therapeutic modalities. Levamisole and its additive therapeutic effect when combined with 5-FU in the treatment of Stage C colorectal carcinoma establishes the potential usefulness of chemicals which specifically augment the immuno response. The explosive growth of cytokine research has led to many technical advances which were key to give cloning and the availability of recombinant cytokines which have extended and modified our concepts of cytokines. The capability of cloning to provide considerable quantities of pure cytokines, permitted studies of immunological, physiological, and therapeutic roles of cytokines. All three classes of immunomodulators: biologicals; chemical; and cytokines will continue to play a major role in advancing and improving the quality of treatment of several of human as well as animal diseases. PMID- 1585423 TI - Modulation by ST 789 of in vitro lymphocyte activation and cytokine production. AB - Our results indicate that ST 789 exhibits complex immunomodulant properties. In fact, we found that ST 789 inhibits the expression of activation antigens, such as interleukin-2 and transferrin receptors by peripheral blood mononuclear cells (PBMCs) from healthy subjects following mitogen stimulation, but we were not able to detect under the same experimental conditions any effect on the in vitro production of soluble CD8 antigen and of interleukin-4 as well as on the proliferative response of antigen-specific and autoreactive human T cell lines. Finally, we showed that ST 789 is able to strongly enhance the in vitro production of interleukin-6 by PHA-stimulated PBMCs. The reduced expression of activation antigens in the presence of ST 789 does not seem to be mediated by CD8+ suppressor T lymphocytes, as indicated by the normal soluble CD8 levels in culture media, but rather reflects a direct inhibitory action on T helper proliferation and likely on interleukin-2 secretion. The strong enhancement by ST 789 of the in vitro interleukin-6 production seems to indicate the most relevant possibility of clinical applications in human diseases. PMID- 1585424 TI - Immunorestorative properties of ST 789 on experimentally immunosuppressed and infected mice. AB - ST 789, a newly synthesized chemical characterized by an aminoacidic group joined to the N9 position of the hypoxanthine ring, has recently been shown to be endowed with immunomodulatory properties. In this study we tested ST 789 in vivo for protective effects in Cyclophosphamide-immunosuppressed CD1 mice experimentally infected with several bacterial and fungal pathogens. We found that immunosuppressed mice infected with either fungi or bacteria were significantly protected, as evaluated both by percent mortality and survival time, when treated with doses of ST 789 even as low as 0.2 mg/kg/day. We also observed a marked synergism when the mice were first treated with ST 789 and then additionally treated with subeffective doses of antibiotics such as Amphotericin B, Ceftazidime, and Gentamicin. Even though further studies are required to elucidate the mechanisms underlying the ST 789 effects, these results show that ST 789 is a very promising new immunomodulator whose therapeutic potential has yet to be fully exploited. PMID- 1585425 TI - The perioperative nurse's role in total knee replacement. AB - 1. Presence of any infection, local or distant, is a contraindication to total knee replacement. 2. Cement may or may not be used in securing the prostheses. 3. Care should be taken in handling implants to avoid scratches, notches, and exposure to lint from towels or drapes. PMID- 1585426 TI - A survey of allied health students' knowledge of HIV and AIDS. AB - 1. The best and only preventative treatment for AIDS is quality, in-depth education. 2. Increasing the knowledge of adolescents and young adults is not easy despite enormous media exposure; many engage in high-risk behaviors, believing themselves to be invulnerable to infection. 3. Although respondents reported that they were knowledgeable about HIV infection, the findings suggest that the participants did not have as solid a knowledge of the disease as expected. PMID- 1585427 TI - Managing stress in the OR. AB - 1. When nurses are particularly stressed, they are often out of touch with many of their potential coping resources. The rediscovery of forgotten skills or the development of new skills for managing stress can significantly reduce stress and thus prevent job burnout and promote vitality. 2. Skills for coping with stress that are primarily internal factors include personal management, outlook, and stamina skills. Relationship skills may be developed to alter the individual's relationship with the environment. 3. Nurses should attempt to match the coping technique to the situation at hand or to their personal strengths and preferences. The most energizing strategy may be to try something new. PMID- 1585428 TI - Physician orientation to the operating room. AB - 1. Registered nurses and technicians in each of the hospital's different services serve as orientators for the physicians, increasing staff job satisfaction. 2. Physician orientation combines OR orientation with general hospital orientation; expands staff educational opportunities; increases awareness of resources; improves interdepartmental affiliations; and encourages satisfaction for physicians. 3. The orientation process recognizes staff as experts, giving them personal recognition. Follow-up gives the OR team a sense of where improvements can be made. PMID- 1585429 TI - Product hazard: microsurgical drills susceptible to electromagnetic interference. PMID- 1585430 TI - Intraoperative management of an infant with a nasofrontal encephalocele. AB - 1. An encephalocele is a congenital malformation in which the structures of the central nervous system, in communication with cerebrospinal fluid pathways, herniate through a cranial defect. 2. Classification of encephaloceles depends on their anatomical location within the cranium, and the prognosis and treatment largely depend on the site of such defects. 3. Although the operation is delayed until the infant gains strength, early correction (within the first month) minimizes facial deformity, prevents further damage to brain tissue herniating through the defect, and increases the chance of normal binocular vision. PMID- 1585431 TI - Prophylactic platelet transfusion. PMID- 1585432 TI - Should all blood from related donors be irradiated? PMID- 1585433 TI - Can the reading for serologic reactivity following 37 degrees C incubation be omitted? AB - The need to detect antibodies that agglutinate and/or hemolyze red cells (RBCs) directly at 37 degrees C, but do not react in subsequently performed indirect antiglobulin tests (IATs), is of concern relative to the streamlining and automation of antibody detection methods. To determine incidence and significance of such reactions, data from 87,480 tests, which used low-ionic-strength saline, 10-minute incubation at 37 degrees C, and anti-IgG, were analyzed for unexpected antibodies. There were 3590 positive tests, of which 475 showed reactions at 37 degrees C but not in subsequently performed IATs (37 + IAT-). Of these, 196 reactions were due to autoantibodies or other factors usually considered insignificant with respect to the survival of transfused incompatible RBCs, 176 were due to alloantibodies of questionable clinical significance (M, Lea, P1, etc.), and 103 were associated with alloantibodies of potential clinical significance (63 E, 27 K, 5 Jka, 4 D, 3 cE, and 1 C). This latter reaction was seen in 72 patients, with two 37 + IAT-antibodies occurring in each of 3 patients. Of the 75 potentially significant 37 + IAT-antibodies, 57 were seen in patients recently exposed to homologous RBCs, 13 in patients with a history of transfusion and/or pregnancy, and 5 in patients with no known exposure to homologous RBCs. IAT reactivity was observed in subsequent samples with 27 of these antibodies. The predictive value of a 37 + IAT-test was 21.7 percent for a potentially significant antibody. The incidence was 0.12 percent of all tests for unexpected antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585434 TI - Impact of blood transfusion and burn injury on microbial translocation and bacterial survival. AB - The role of the immune system in microbial translocation must be clarified. In these studies, the effect of blood transfusion-related immunosuppression on translocation was investigated in a burn animal model previously known to increase the gut's permeability to 14C-radiolabeled Escherichia coli. In a first experiment, Balb/c mice underwent transfusion (T) with 0.2 mL per mouse of allogeneic C3H/HeJ mouse blood 5 days prior to undergoing 30-percent burn injury (B) and simultaneous gavage (G) with 10(9) E. coli bacteria labeled with 14C. An additional six groups of Balb/c mice underwent different combinations of T, B, and G procedures (TG, BG, TB, T, B, G). Survival rate was recorded for all groups on Day 10. This experiment suggested that B and T, to a lesser extent, were the factors affecting survival, although the combination of T, B, and G clearly showed a synergistic effect on mortality. In a second experiment, 18 Balb/c mice belonging to TBG, BG, TG, and G groups were sacrificed 1, 4, and 24 hours after burn or gavage. The residual radioactivity and the percentage of viable bacteria were computed for mesenteric lymph nodes, spleen, liver, lungs, blood, and peritoneal fluid. Statistical analysis of the radionuclide counts recognized B as the only variable able to enhance the magnitude of 14C E. coli translocation. The percentage of viable bacteria showed that T and, more moderately, B were the factors leading to the failure of bacterial clearance in the tissues. PMID- 1585435 TI - Blood transfusion and postoperative infection in orthopedic patients. AB - Adverse effects of the transfusion of homologous blood on tumor recurrence and resistance to bacterial infection have been reported previously, but the findings are inconclusive. A retrospective review of patients undergoing orthopedic surgery was conducted, and the rate of the postoperative infectious complications was compared among those receiving homologous blood, autologous blood, both types, or no transfusion support. An overall postoperative infection rate of 6.1 percent was observed: 6.9 percent among persons receiving homologous blood, 5.0 percent among those receiving autologous blood, 11.9 percent among those receiving both homologous and autologous blood, and 4.9 percent among those not receiving transfusions (p = 0.37). Among patients receiving homologous blood, a subset of 15 patients received homologous whole blood and had an infection rate of 20 percent. Significant predictors of postoperative infection included increasing age, spinal surgery, high admission hematocrit, and greater time in surgery. Of factors relating to transfusion, only the use of homologous whole blood was a significant predictor of postoperative infection, which suggests a detrimental effect of homologous plasma. It can be concluded that, in this group of patients undergoing relatively nontraumatic surgery, several variables that are not related to transfusion, as well as the use of homologous whole blood, were significant predictors of postoperative infection. PMID- 1585436 TI - Transfusion-associated graft-versus-host disease: do transfusions from second degree relatives pose a greater risk than those from first-degree relatives? AB - When a patient receives blood from a closely related donor, there is the potential for transfusion-associated graft-versus-host disease (TA-GVHD). With a mathematical model, the potential risk of TA-GVHD was derived for six classes of related donors. This risk was considered to be present when an HLA-heterozygous patient received blood from a donor who was homozygous for one of the patient's haplotypes. Calculations showed that second-degree related donors present a greater risk of TA-GVHD than some (siblings) but not all (parents, children) first-degree related donors. Moreover, there is, in general, no sharp cutoff of risk among the various classes of donors. These results should be considered in the determination of a policy for the irradiation of directed-donor units. PMID- 1585437 TI - In vitro and in vivo evaluation of cotton wool filtration of platelet concentrates obtained by automated and manual apheresis. AB - The effect of cotton wool filtration of apheresis platelet concentrates (PCs) on platelet viability and complement activation was evaluated by two laboratories. PCs were prepared by automated (Lab A, n = 5) or manual (Lab B, n = 5) apheresis. After storage for 1 day, the PC was filtered through cotton wool before transfusion on one occasion and, on the other occasion, filtered through a standard screen filter before transfusion to the same donor. Five paired studies were performed by each laboratory. Except for a small, but significant reduction in mean platelet size, from 7.3 +/- 1.1 to 6.6 +/- 0.9 microns 3, after cotton wool filtration, no effect of filtration on various tests of in vitro platelet function and morphologic integrity was found. As demonstrated by autologous radiolabeled studies, no effect of cotton wool filtration on platelet viability was found by Laboratory B, while Laboratory A found a slight increase in the percentage of recovery from 59 +/- 4 to 68 +/- 13 percent, and a small reduction in survival, from 8.2 +/- 0.9 to 7.7 +/- 0.5 days after cotton wool filtration (p less than 0.05). Cotton wool filtration was associated with a slight increase in C3a levels found in manual apheresis PCs. Neither laboratory found any effect of cotton wool filtration per se on the recipients' white cell (WBC) counts or C3a and C5a levels after transfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585438 TI - The effect of prestorage white cell reduction on the function and viability of stored platelet concentrates. AB - The role of residual donor white cells (WBCs) in producing the storage lesion of platelets used for transfusion was studied. The effect of prestorage WBC reduction on in vitro and in vivo measurements of the quality of stored platelet concentrates (PCs) was examined by using a newly developed WBC-reduction filter capable of preparing PCs with a mean residual WBC concentration of less than 1 per microL. For in vitro studies, a triplet study design was used, in which WBC reduced PCs were matched to standard PCs and to WBC-enriched PCs obtained from the same donor at the same phlebotomy. Twelve donors were studied. Prestorage WBC reduction resulted in a higher pH and pO2 and a lower pCO2 than in standard PCs. In accord with previous in vitro studies, a significant rise in plasma glycocalicin and lactate dehydrogenase was measured during storage, but the levels were not significantly different in WBC-reduced PCs and standard PCs. Platelet aggregation and ATP release in response to graded doses of thrombin was similar in WBC-reduced and standard PCs. In vivo recovery and survival studies were comparable in WBC-reduced and standard PCs. Although the residual donor WBC content of PCs has a significant impact on storage pH, pO2, and pCO2, prestorage WBC reduction does not affect platelet structure, function, or viability as assessed by in vitro or in vivo measurements. PMID- 1585439 TI - Postfiltration factor VIII and fibrinogen levels in cryoprecipitate stored at room temperature and at 1 to 6 degrees C. AB - The 13th edition of the standards of the American Association of Blood Banks specified storage at 1 to 6 degrees C for cryoprecipitated anti-hemophilic factor (Cryo) administered up to 6 hours after thawing if the Cryo is used for factor VIII (FVIII) content (Standard J4.210). Previous editions specified room temperature (RT) storage for up to 6 hours. Currently, the temperature specification has been deleted. There are few data addressing the optimal storage temperature and maximum storage time for FVIII and fibrinogen in thawed Cryo. Thirty bags of Cryo were assayed for FVIII and fibrinogen. Each bag was divided into two aliquots; one was stored at RT and the other at 1 to 6 degrees C. Assays were performed immediately after thawing (Base) and 6 and 24 hours after thawing, respectively. All samples were filtered through 200-mu blood component infusion sets before assay. Three hundred analyses were performed, 150 each for FVIII and fibrinogen by conventional clotting technique. Data were analyzed by using a paired t test. Cryo stored at 1 to 6 degrees C for 6 and 24 hours showed an FVIII loss of 35 percent (p less than 0.0001) and 63 percent (p less than 0.0001), respectively. Cryo stored at RT for 6 and 24 hours had an FVIII loss of 8 percent (p greater than 0.05) and 20 percent (p less than 0.0001). Cryo stored at 1 to 6 degrees C for 6 and 24 hours had a fibrinogen loss of 20 percent (p less than 0.0001) and 43 percent (p less than 0.0001). Cryo stored at RT for 6 hours had no fibrinogen loss and a 2 percent loss at 24 hours (p greater than 0.05). These preliminary data show a significant loss of FVIII and fibrinogen activity in Cryo stored at 1 to 6 degrees C and filtered before assay. The FVIII and fibrinogen activity at RT is clearly maintained up to 6 hours after thawing. PMID- 1585440 TI - The extension of 4 degrees C storage time of frozen-thawed red cells. AB - Blood was drawn from volunteer donors and frozen using the high glycerin, mechanical freezing procedure accepted by the United States Navy. Subsequently, the units of blood were thawed and washed. Various anticoagulants were added, and the red cells were stored in a refrigerator at 4 degrees C for periods of up to 28 days. Chemical analyses were performed periodically. These showed that the addition of the anticoagulants ACD, CPD and CPDA-1 caused the red cells to be preserved better than the currently accepted 0.9-percent NaCl, 0.2-percent glucose solution. In vivo 51Cr viability studies performed on blood stored with CPDA-1 for 14 days showed a 24-hour viability of 78.8 +/- 8.4 percent. In a subsequent study, the blood was stored for 21 days prior to freezing and then was rejuvenated and frozen. The cells were thawed, washed, and stored at 4 degrees C with CPDA-1 for an additional 14 days. The 24-hour viability of these cells was determined to be 74.0 +/- 5.1 percent. These findings show that the postthaw storage time of red cells can be increased greatly over the now-accepted 24 hours, if bacterial sterility can be assured. PMID- 1585441 TI - Separation of albumin from autologous plasma by heat. AB - A simplified technique has been developed to separate albumin from the plasma of a patient undergoing treatment with plasma exchange. This albumin can be returned to the patient to maintain colloid osmotic pressure without risk of transmitting disease. Patient plasma is obtained by apheresis. It is heated at 70 degrees C for 60 minutes to denature and remove autoantibodies, immune complexes, and abnormal globulins. The resulting low-concentration albumin solution (LCAS) retains its natural properties. Immunologic analysis by gel diffusion shows a reaction pattern of complete identity with that of human serum albumin. The albumin in LCAS is more than 90 percent of the remaining protein, as determined by scan of a cellulose acetate electrophoresis pattern. More than 97 percent of the albumin is in monomer form, as judged by polyacrylamide gel electrophoresis. No patient antibodies to neonantigens in the heat-treated albumin can be identified by double radial immunodiffusion. More than 80 percent of the plasma albumin is recovered in LCAS. LCAS is safe and efficient for use in plasma exchange. PMID- 1585442 TI - Lipid peroxidation in stored red cells. AB - Lipid peroxidation is initiated by the production of oxygen-free radicals; it is increased in a wide variety of diseases, including various hemolytic anemias, and in hemoglobin disorders. Increased lipid peroxidation occurs in red cells in the presence of reactive iron species and some heme moieties. In this study, greatly reduced concentrations of malondialdehyde, an indicator of lipid peroxidation, were observed in stored blood upon the addition of both deferoxamine mesylate and diethylenetriaminepentaacetic acid (p less than 0.001). The antioxidant glutathione was much less effective (p less than 0.01 or less than 0.05, depending on incubation time). On the other hand, the addition of dimercaptosuccinic acid and ascorbic acid both significantly increased malondialdehyde production over controls (p less than 0.001 and p less than 0.05, respectively). Ascorbic acid, in the presence of deferoxamine mesylate, added no red cell protection over that of deferoxamine mesylate alone. The addition of metal chelators and, possibly, certain antioxidants to stored blood may be effective in increasing the viability and longevity of transfused red cells. PMID- 1585443 TI - Transfusion-associated graft-versus-host disease in a presumably immunocompetent patient after transfusion of stored packed red cells. AB - A 54-year-old woman developed transfusion-associated graft-versus-host disease (TA-GVHD) after the transfusion of stored packed red cells obtained from unrelated donors. The patient was presumed to be immunocompetent. A diagnosis of TA-GVHD was made by clinical features and postmortem pathologic findings. Sex chromatin analysis of the patient's lymphocytes demonstrated chimerism. HLA typing of the blood donors revealed one to be HLA-homozygous for one of the patient's HLA haplotypes (A33-B44-Cblank). This case illustrates the risk in the general patient population of TA-GVHD after routine blood transfusion therapy. Workers should be aware of this possibility and should continue searching for an efficient way to prevent it. PMID- 1585444 TI - Anti-idiotypic antibodies and regulation of immune responses. PMID- 1585445 TI - Controversies in transfusion medicine. Prophylactic platelet transfusion therapy: pro. PMID- 1585446 TI - Controversies in transfusion medicine. Prophylactic platelet transfusion revisited after 25 years: con. PMID- 1585447 TI - Auto-anti-M causing immune hemolysis in vitro. PMID- 1585448 TI - How does protein phosphorylation regulate photosynthesis? AB - Phosphorylation of light-harvesting antenna proteins redirects absorbed light energy between reaction centres of photosynthetic membranes. A generally accepted explanation for this is that electrostatic forces drive the more negatively charged, phosphorylated antenna proteins between membrane domains that differ in surface charge. However, structural studies on soluble phosphoproteins indicate that phosphorylated amino acid side chains have specific effects on molecular recognition, by ligand blocking or by intramolecular interactions which alter protein structure. These studies suggest alternative mechanisms for phosphorylation in control of pairwise protein-protein interactions in biological membranes. Thus, in photosynthesis, the surface charge model is only one possible interpretation. PMID- 1585449 TI - Golgi localization signals. PMID- 1585450 TI - A tablecloth-sized model E. coli. PMID- 1585451 TI - Close parallels in allergic diseases. PMID- 1585452 TI - Transcribed chromatin. AB - In eukaryotes, DNA that is transcribed is packaged first into nucleosomes and then into chromatin fibres. How does transcription proceed through chromatin? Studies of transcription through nucleosomes in vitro suggest that the intracellular environment may provide factors which alleviate the inhibitory effect that nucleosomes have on transcription, possibly via positive supercoiling induced by the migrating polymerase. Stable changes in nucleosome structure have been correlated with transcriptionally active chromatin, but the precise mechanism by which RNA polymerase transcribes through nucleosomal DNA remains unknown. PMID- 1585453 TI - Selective membrane protein trafficking: vectorial flow and filter. AB - Membrane proteins trafficking along cellular pathways encounter molecular filters. These filters can introduce them to new pathways and thus direct them towards new destinations. Many proteins carry molecular signals within their cytoplasmic domains that allow them to be selected by the filters. The detailed characterization of these signals is providing new insights into the pathways themselves and indicating the locations of other, as yet unidentified filters. PMID- 1585454 TI - Metabolic control of gene expression: in vivo studies with transgenic mice. AB - Transgenic animals provide a comprehensive model for investigating genes encoding inducible enzymes involved in metabolism, since the molecular mechanisms regulating gene transcription can be studied in the whole animal. Studies on the promoters of the genes encoding two key enzymes in the gluconeogenic and glycolytic pathways--phosphoenol-pyruvate carboxykinase and pyruvate kinase are described as examples of this approach. Work on the phosphoenolpyruvate carboxykinase promoter using transgenic mice has been particularly informative: the cis-acting elements involved in hormonal regulation, tissue specificity and developmental inhibition of gene expression have been identified and their function in vivo examined. PMID- 1585455 TI - Closed circular DNA as a probe for protein-induced structural changes. AB - Biological systems are replete with examples of DNA formed into a closed loop structure, either alone or in close association with proteins. Such closed circular DNA molecules are subject to a topological constraint that modifies, often in a major way, the structure and reactivity of the DNA. The topological constraint also permits closed circular DNAs to be used as analytical tools to learn about the structure of DNA-protein complexes. PMID- 1585456 TI - A module of the DnaJ heat shock proteins found in malaria parasites. PMID- 1585457 TI - Molecular flypaper and atherosclerosis: structure of the macrophage scavenger receptor. AB - Macrophage scavenger receptors have been implicated both in the deposition of lipoprotein cholesterol in artery walls during the formation of atherosclerotic plaques and in host defense against pathogenic infections. The receptor's unusual ability to bind tightly to a very wide variety of ligands and its novel mosaic structure comprising alpha-helical coiled-coil, collagenous and cysteine-rich domains are described. PMID- 1585458 TI - Mammalian hormones in microbial cells. AB - Hormones and hormone-binding proteins resembling those of vertebrates are widespread in fungi, yeast and bacteria. Functional responses of microbial cells to mammalian hormones have also been found. The evolutionary roots of the vertebrate endocrine system may, therefore, be far more ancient than is generally believed. PMID- 1585459 TI - Herbicide binding in the bacterial photosynthetic reaction center. AB - The ureas and phenolics are two major classes of herbicides that act on Photosystem II (PSII) and are normally inactive in the photosynthetic reaction centers of purple bacteria. However, the triazine-resistant mutant T4 from Rhodopseudomonas (Rps.) viridis, which has the tyrosine residue at position 222 on the L subunit substituted for phenylalanine (TyrL222Phe), is sensitive to both ureas and phenolics. Since for the first time structural data on urea binding are available, T4 is a particularly interesting model for the herbicide-binding site of PSII. PMID- 1585461 TI - Structural and functional relationships between aminoacyl-tRNA synthetases. AB - Aminoacyl-tRNA synthetases can be divided in two groups of equal size on the basis of differences in the structure of their active sites. The core of class I synthetases is the classical nucleotide-binding domain with its characteristic Rossmann fold. In contrast, the active site of class II synthetases is built around an antiparallel beta-sheet, to which the substrates bind. This classification, which is based on structural data (amino acid sequences and tertiary structures), can be rationalized in functional terms. PMID- 1585460 TI - Clusterin: the intriguing guises of a widely expressed glycoprotein. AB - The glycoprotein clusterin has recently entered the scientific arena in diverse guises. It forms high-density lipoprotein complexes with apolipoprotein A-I, participates in the terminal complement reaction and serves as a granule constituent in neuronal and endocrine cells. Apically secreted, it is also found in the male reproductive tract and the tubular lumen of epithelial ducts. Thus, it may serve important functions in tissue remodelling, immune defense and transport of biologically active peptides. PMID- 1585462 TI - Host-donor interactions in healing of human split-thickness skin grafts onto nude mice: in situ hybridization, immunohistochemical, and histochemical studies. AB - The behavior of host and donor cell lines in human split-thickness skin grafts onto nude mice was studied by in situ hybridization (ISH) using genomic DNAs as probes, and immunohistochemically with species-specific or cross-species specific antibodies, at different stages ranging from day 3 to more than 1 year following grafting. Changes in the graft vascular and interstitial extracellular matrix were also assessed using species-specific or cross-species specific antibodies to human or murine type I, III, and IV collagens. Finally, transplant reinnervation was investigated using antibodies to various nerve cytoplasmic antigens and the thiocholine method to demonstrate acetylcholinesterase. Using these methods we were able to show the following: (1) the graft epidermis that is not replaced by mouse keratinocytes is progressively colonized by recipient Langerhans cells (LCs); (2) revascularization of the grafts begins soon by inoculation of the graft vessels with the host microcirculatory bed, and mouse endothelial cells growing into preexisting human capillary tubes produce a new basement membrane, prior to the replacement of the original one; (3) within 3-5 days following grafting, mouse fibroblasts migrate into the graft dermis. The density of the human and murine fibroblast populations then progressively increases. Characterization of the interstitial collagens identifies both human and murine type I and III collagens. Production of type III collagens decreases during the progression of fibrogenesis while human type I collagen becomes the predominant matrix protein; (4) transplant reinnervation is deficient, and neurites growing into severed graft nerve trunks were never detected. PMID- 1585463 TI - Ex vivo versus in situ resection of segmental liver grafts in pigs--a comparison in immediate and four-hour-stored grafts. AB - This study compared the function of reduced grafts prepared in situ or ex vivo and transplanted immediately or after 4 hr of cold storage. Measurements of acid/base balance, plasma electrolytes, albumin, and urea showed no differences between groups. There was no difference between the increase and decline of plasma AST in recipients of grafts transplanted immediately after either ex vivo or in situ reduction; the increase in plasma AST of recipients of stored grafts was up to 10-fold and persisted until the end of the study at 7 days, with some decline. Plasma fibrinogen decreased intraoperatively but levels were restored within 24 hr in all groups; plasma prothrombin and partial thromboplastin times were not significantly disturbed. The patterns of decline and return of tissue adenine nucleotides were similar in all groups. While the regenerative response measured by tissue thymidine kinase and mitotic figures was not different between the groups, comparison with results from a group of partially hepatectomized animals showed a 3-4-fold depression in response in reduced liver grafts. The contributions of the effects of ischemia, flushing, and preservation to the depressed regenerative response of reduced liver grafts need to be determined. The present studies suggest however, that with regard to functional assessment, results are not affected either by ex vivo or in situ reduction of the graft, or by cold storage for 4 hr. PMID- 1585464 TI - Suppression of kidney allograft rejection across full MHC barriers by recipient specific antibodies to class II MHC antigens. AB - The aim of these studies was to see if recipient-specific antibodies to class II MHC antigens might be effective in suppressing kidney graft rejection in rats. For these experiments, the polymorphic BMAC-4 mouse IgG1 monoclonal antibody to RT1-D class II MHC antigens was raised. This antibody reacts with the DA, LEW, PVG, and SHR strains, but not the BN or WAG strains, and is therefore recipient specific in the WAG to PVG combination. Initial in vivo titrations demonstrated that 1 ml doses of the BMAC-4 and also of the MRC OX6 (monomorphic mouse IgG1 anti-RT1-B class II) antibody resulted in the maintenance of free antibody levels in blood for greater than 24 hr. Treatment of PVG recipients of WAG kidney allografts with the BMAC-4 antibody, but not the MRC OX6 antibody, resulted in greatly prolonged graft survival. To examine possible mechanisms, several experiments were performed. After intravenous injection, the antibody was found to have ready access to the connective tissues of nonlymphoid organs, to the red and white pulp of the spleen, and to the medulla of lymph nodes. However, there was poor early access to the cortex and paracortex of lymph nodes. Both MRC OX6 and BMAC-4 could completely suppress PVG anti-WAG and WAG anti-PVG mixed lymphocyte culture reactions. Both antibodies were also equally effective for opsonisation of class II-positive cells from the blood circulation. However, only the recipient-specific, anti-RT1-D BMAC-4 antibody suppressed graft rejection. Thus, while the BMAC-4 antibody is likely to have had a variety of different effects on RT1-D positive recipient cells, the locus specificity of the immunosuppression is consistent with an important component of those effects being the blocking of presentation of WAG donor alloantigens by PVG RT1-D class II antigens on PVG antigen-presenting cells. PMID- 1585465 TI - Dynamics of glycemic normalization following transplantation of incremental islet masses in streptozotocin-diabetic rats. AB - We examined the dynamics of glycemic normalization following intraportal infusion of an incremental number of islets of Langerhans in male Wistar-Furth rats. Non fasted plasma glucose, 24-hr urine volume, and body weight were determined weekly during three weeks of streptozotocin-induced diabetes and for 5 weeks following transplantation of 250-3000 freshly isolated islets. At one week following transplantation, urine volume was inversely proportional to the mass of islets transplanted, but by 5 weeks posttransplantation urine volume was near-normal except in rats receiving only 250 islets. On the basis of the mean data, the nonfasted plasma glucose fell linearly at a rate of 66 mg/dl per week in rats receiving 500-1000 islets, with normoglycemia (147 +/- 9 mg/dl) being obtained 5 weeks posttransplantation. Examination of the individual time courses for nonfasted plasma glucose revealed a different pattern of glycemic normalization, which consisted of sustained hyperglycemia followed by a rapid fall in the plasma glucose level. During the week prior to normalization glucose fell at a rate of 170 mg/dl per week and normoglycemia was obtained from 1 to 5 weeks following transplantation. Examination of the frequency distribution of nonfasted glucose levels suggested a threshold of 300 mg/dl for glycemic normalization. We conclude that the dynamics of glycemic normalization following transplantation of a suboptimal islet mass include sustained hyperglycemia of variable duration, followed by a rapid fall in the nonfasted plasma glucose level. The contributions of changes in insulin secretion and insulin action underlying this dynamic behavior remain to be determined. PMID- 1585466 TI - Psychiatric and social consequences of liver transplantation. AB - We assessed the prevalence of psychiatric morbidity and level of social adjustment in 32 of 34 adults who received liver transplants between 1 August 1987 and 31 July 1988 and who survived more than 6 months postoperatively. The prevalence of psychiatric morbidity was comparable with that found in the general population. Subjective complaints of cognitive impairment were common (40.6%). Liver transplant recipients were not significantly more handicapped in overall social functioning, but did show significant impairment in several role areas when compared with a community sample. Psychiatric morbidity was associated with greater social impairment, whereas liver function and other medical problems were not. We suggest that identification and treatment of psychiatric illness following transplantation needs to be better established as part of the treatment program. PMID- 1585467 TI - Public and private insurer designation of transplantation programs. AB - In an effort to assure quality and contain costs, several major private health insurers now restrict payment of transplantation procedures to designated programs, often referred to as centers of excellence. These insurers underwrite coverage for over 100 million people. Few transplantation programs meet the criteria set forth by insurers, thus raising concerns about patient access to care. The criteria being used by five private insurers and Medicare were obtained and reviewed. Insurers now designate kidney, heart, liver, heart-lung, pancreas, and bone marrow transplant programs based upon total annual transplant volume as well as one- and two-year patient and graft survival rates. Transplant center criteria vary according to procedure and type of recipient (i.e., pediatric vs. adult). Most insurers require hospitals to perform a minimum of at least 6, and up to 50 procedures annually. Expected one-year patient survival rates may exceed 90% and are often higher than 80%, although standards are usually lower for heart lung and bone marrow transplantation. In addition, if centers meet the minimum volume and outcome criteria, insurers expect transplant centers to discount per procedure changes by as much as 25%. Patients are often offered incentives to use designated centers with insurers frequently paying travel costs and reducing or waiving copayment amounts. The designation of transplant programs by third-party payers has merit, although program volume requirements may have less validity than individual transplant surgeon and physician experience. Other problems are also apparent. For example, discount pricing is suspect, given the lack of data on actual transplant procedure costs. Also, some insurers intend to regionalize transplant programs, thus unnecessarily limiting patient access to care. Alternatively, the concentration of transplant activity at a smaller number of centers may enhance research opportunities. Nonetheless, transplant professionals, hospital administrators, and patient advocates remain wary of insurer objectives. There is concern that the designation of centers is simply another method by which insurers can avoid paying for transplants. PMID- 1585468 TI - The relationship of mast cells and their secreted products to the volume of fibrosis in posttransplant hearts. AB - A series of 96 posttransplant endomyocardial biopsies taken from 11 patients was subjected to quantitative analysis of mast cells and fibrosis. Ultrastructural analysis showed that mast cell numbers were increased and there was obvious degranulation in some posttransplant hearts. Activated mast cells and their secreted products, which contain heparin and histamine, are toxic to the hearts and may contribute to interstitial and perimyocytic fibrosis. The numbers of mast cells and granules were correlated with volume of fibrosis (r = 0.63, P less than 0.025; r = 0.73, P less than 0.01). There were differences between the release of mast cell granule contents seen in the posttransplant hearts and the rapid and massive reaction of anaphylactic degranulation of mast cells. Some mast cells progressively lost their dense granule contents, displaying a variety of piecemeal degranulation that indicates a slow degranulation process. These events occurred from the first week; they lasted from weeks to months. The fibrosis developed quickly in the cases with more mast cells and degranulation. The cases with fewer mast cells and granules showed only mild increases in the volume of fibrosis. Mast cells appeared as early as the first posttransplantation week. Patients with greater numbers of mast cells underwent more severe rejection episodes. This study demonstrated that mast cells play an early and important role in the perimyocytic and interstitial fibrosis of posttransplant hearts. Mast cells may also be important in the inflammatory process of rejection reaction. The severity of fibrosis appears related to the density of mast cells and their granules. PMID- 1585470 TI - Inhibition of in vitro immunoglobulin production by rapamycin. AB - Like FK506, rapamycin, a structural analog of FK506, is a strong immunosuppressant. The immunosuppressive effect of Rapa in in vitro IgG, IgM, and IgA production by human lymphocytes was examined in this study. To inhibit spontaneous or pokeweed mitogen-stimulated production of Ig by human peripheral blood lymphocytes, about one thousandfold lower concentrations of Rapa (IC50 = 0.3 nM-2 nM) were required than of cyclosporine (IC50 = 0.3 microM-2 microM). T cells were the direct targets of Rapa, because preincubation of T cells with Rapa abolished the T cells helper effect to T-dependent Ig production. Rapa also had direct suppressive effect on B cells, since Rapa suppressed IgG production by pure B cells stimulated with IL2 and Staphylococcus aureus Cowan I. Kinetic studies measuring IgG production and cell proliferation revealed that Rapa acted at the activation stage of T and B cells. Exogenous IL2 substantially reversed the inhibitory effect of CsA but not that of Rapa in Ig production. This study is the first report on the strong suppressive effect of Rapa on human humoral immune response with a quantitative comparison with that of CsA. The underlying mechanisms are also explored. The results indicate the potential usefulness of this drug in treatment of presensitized transplantation patients, with whom cytotoxic Ab is a major obstacle to a successful transplantation. PMID- 1585469 TI - The importance of thiopurine methyltransferase activity for the use of azathioprine in transplant recipients. AB - The immunosuppressive efficacy of azathioprine is related to its rapid metabolism in vivo to 6-mercaptopurine (6MP), with subsequent conversion to thioguanine nucleotides by an anabolic route involving hypoxanthine-guanine phosphoribosyltransferase. Two alternative catabolic routes exist: oxidation to 6 thiouric acid via xanthine oxidase and methylation to 6-methylmercaptopurine via the enzyme thiopurine methyltransferase (TPMT). Catabolism via either route would restrict formation of the active metabolites. We analyzed TPMT activity in erythrocyte lysates of 25 controls, 25 uremic patients on dialysis, and 68 transplanted patients. Median activity was lower in controls (31.0 pmol/hr/mg Hb, range 16.2-43.0) and transplanted patients receiving only cyclosporine and prednisolone (31.7 pmol/hr/mg Hb, range 12.7-43.5) than in the azathioprine treated group, (36.1 pmol/hr/mg Hb, range 16.1-71.3), or the uremic group on dialysis, (35.5 pmol/hr/mg Hb, range 18.6-62.6) suggesting that both azathioprine and uremia induce the enzyme, but CsA does not. Only 3 patients demonstrated total intolerance to azathioprine, 2 of whom had very low TPMT activity (zero and 12.7 pmol/hr/mg Hb). The intolerance of the third patient, despite high TPMT activity, was attributed to concomitant cotrimoxazole therapy. Patients with intermediate activity (15-26 pmol/hr/mg Hb) could tolerate azathioprine well. Of 29 cadaver recipients given only azathioprine plus prednisolone, 24 with a better clinical outcome had a significantly lower activity (33.1 pmol/hr/mg Hb, range 16.1-46.1) than 5 with reduced allograft function (42.5 pmol/hr/mg Hb, range 33.8 51.5). TPMT activity in these 24 patients was also significantly lower than the general group of azathioprine-treated recipients. This inverse association between TPMT activity and allograft function was again found among 30 patients receiving triple therapy (azathioprine, CsA, prednisolone). Self-selection of the best recipients for azathioprine immunosuppression apparently occurred, based on low catabolism of the drug. We conclude that total intolerance to azathioprine is rare and usually appears in patients with very low TPMT activities. Our results also suggest that the wide range of TPMT activity may be an important factor in determining long-term graft survival in azathioprine-treated patients; those with high activity might benefit from doses near the upper limit generally recommended. PMID- 1585471 TI - Induction of HLA class II antigen and interleukin 2 receptor expression in acute vascular rejection of human kidney allografts. AB - The induction of HLA class II antigens on graft tubular cells and IL-2 receptor expression on the infiltrating lymphoid cells was studied in 245 prospective aspiration biopsies taken during the first posttransplant month from 20 human renal allografts with histologically verified acute vascular rejection (AVR). Based on the histological findings, the specimens were categorized into two main groups: biopsies from grafts with features of AVR only, and biopsies with a combination of AVR and acute cellular rejection (ACR). Also in the second group the AVR findings were predominant. Biopsies were further divided into two subgroups, depending on whether the rejection was reversible or irreversible. Evaluation of class II and IL-2R expression was done by indirect immunoperoxidase staining using monoclonal antibodies. The initial posttransplant tubular cell class II expression was low in all 20 grafts, with 5-15% positive tubular cells, and IL-2R expression was negative. All 13 grafts with a combination of AVR and ACR displayed class II induction, closely correlating to the blast response, with 50% positive tubular cells on days 2-7 after the onset of rejection, and declining thereafter back to prerejection level in grafts with reversible rejection. In grafts with irreversible rejection, tubular cell class II expression remained elevated. A similar pattern was observed with regard to IL-2R expression: the IL-2R positive cells disappeared from the grafts with reversible rejection, but they persisted in the irreversible rejections. The same pattern of class II and IL-2R expression was observed in grafts with pure AVR and reversible rejection. Instead, completely different findings were seen in grafts with pure AVR and irreversible rejection: there was neither class II induction on tubular cells nor IL-2R expression on lymphoid cells. The persistant inflammation was dominated by mononuclear phagocytes, and no blast response could be detected during the entire follow-up. These findings demonstrate a close relationship between IL-2R expression and tubular cell class II induction also in AVR, in the majority of cases. On the other hand, the findings in grafts with pure AVR in histology and irreversible rejection suggest that AVR is a heterogenous group of rejections, where different cellular and molecular mechanisms are operating. PMID- 1585472 TI - Effects of cyclosporine on cerebral blood flow and metabolism in dogs. AB - Neurological side effects associated with cyclosporine immunosuppressive therapy are generally believed to occur with CsA blood concentrations above the therapeutic range. The effects of high blood CsA levels on cerebral hemodynamics, metabolism, and electrophysiologic activity were studied in acute (no CsA prior treatment) and chronic (with CsA prior treatment) dogs. In acute animals, when parenteral CsA (10 mg/kg or 25 mg/kg) was administered intravenously (CsA blood level 2000-22,000 ng/ml), slight but significant time-dependent decreases in cerebral blood flow (CBF), prolongation of absolute latencies of somatosensory evoked potential (SSEP), and brainstem auditory-evoked responses (BAER) were noted. In the CsA chronically administered animals (oral CsA 25 mg/kg/24 hr for 14 days, CsA blood level 1077 ng/ml), baseline cerebral physiologic parameters were normal, and the cerebral responses to further administration of CsA (25 mg/kg, CSA blood level 56,000 ng/ml) intravenously were similar to those of the acute animals. Animals given Cremophor EL, the solvent for parenteral CsA preparation, showed similar cerebral responses to those observed in animals given CsA. Thus this study showed that CsA, regardless of the dose given, whether chronically or acutely administered, or the solvent for CsA all induced similar cerebral physiologic responses. We suggest that the cerebral physiologic and functional changes associated with parenteral CsA administration were small and were likely caused by its solvent, Cremophor EL, rather than CsA itself. Furthermore on the basis of our results, it is unlikely that high blood CsA per se can account for neurological side effects that occur in immunosuppressed patients. PMID- 1585473 TI - Prevention of recurrent autoimmune diabetes in the BB rat by islet transplantation under the renal capsule. AB - Pancreatic islet grafts transplanted into subjects with spontaneous autoimmune diabetes are threatened by two immune responses, allograft rejection and the recurrence of autoimmune insulitis. To examine the recurrent autoimmune response to transplanted islets it is necessary to exclude islet allograft rejection. The BB rat is a unique model of spontaneous diabetes with clinical and pathological characteristics identical or similar to those found in human insulin dependent diabetes mellitus (IDDM). In this study we demonstrate permanent acceptance of histocompatible islet grafts in chemically induced diabetes and a lack of intracolony tissue antigen rejection in our BB rat colony. Therefore the vigorous destruction of transplanted BB islets in the liver of spontaneously diabetic BB rats is due to recurrence of diabetes. This recurrence can be prevented by transplantation of islets under the renal capsule. This may be important for clinical application in IDDM, particularly with regard to host and donor tissue matching. PMID- 1585474 TI - Reduction of nutrient absorption in normal rats by cyclosporine. AB - The indications for using cyclosporine are expanding rapidly beyond immune suppression for transplantation. We have previously described reduced active glucose uptake by small bowel following CsA treatment in rats. This study examined the effect of varying the dose and route of administration of CsA on bowel function. Male Lewis rats were given CsA via subcutaneous injection at doses of 5 mg/kg or 30 mg/kg on alternate days, or orally via gavage at 0 (control solvent oil), 7.5 mg/kg, or 30 mg/kg daily. Weight gain and feed intake were followed for 1 month when a balance study was performed to quantify in vivo nutrient absorption from the feed. In vitro studies of glucose and fatty acid uptake studies were then performed. Weight gain was reduced by high-dose CsA whether given orally or by subcutaneous injection. Oral CsA reduced in vivo fat and energy absorption from the diet, and all doses and routes of administration of CsA caused a reduction in both active glucose uptake and passive fatty acid absorption by the bowel in vitro. Thus, CsA has significant effects on bowel function in the normal rat. We suggest that further studies are indicated to determine the effects of CsA in man, especially in conditions with already impaired bowel function. PMID- 1585475 TI - Humoral tolerance in xenogeneic BMT recipients conditioned by a nonmyeloablative regimen. AB - We have recently demonstrated that mixed xenogeneic chimerism and donor-specific tolerance can be produced across a species barrier using a nonmyeloablative conditioning regimen (1). This regimen involves pretreatment of B10 mice with mAbs against CD4+, CD8+, Thy1+, and NK1+ cells, followed by a low dose (3 Gy) of whole-body irradiation and a higher dose (7 Gy) of local irradiation to the thymus and administration of T cell-depleted (TCD) F344 strain rat BMC. Although initial mixed chimerism and de novo maturation of donor rat T cells can be demonstrated in such animals, chimerism is gradually lost, and is no longer detectable by 6 months following BMT (1). When rat skin was grafted onto such animals 4 months following BMT, however, donor-specific skin graft survival was markedly prolonged, while non-donor type rat skin grafts were rapidly rejected (1). These results suggested that a state of donor-specific T cell tolerance existed, and that loss of chimerism was not due to a T cell-mediated immune mechanism. In order to evaluate the possibility that a humoral mechanism might mediate delayed loss of xenogeneic bone marrow grafts, we have now examined sera at various times for the presence of antibody against donor cells. Groups of animals not receiving the complete tolerizing mAb pretreatment regimen produced antidonor lymphocytotoxic antibody in response to BMT and skin grafting. Flow cytometric studies demonstrated high levels of IgM and of IgG of all subclasses against rat BMC and spleen cells in these control mice immunized by BMT. In contrast, such antibodies were not detectable in sera from animals receiving BMT following pretreatment with the tolerance-inducing mAb regimen. Furthermore, the tolerant animals did not develop cytotoxic antibodies or high levels of IgM or IgG against donor BMC after loss of hematopoietic chimerism. Donor-type skin grafts were eventually rejected, but rejection of these and repeat skin grafts did not lead to a cytotoxic antibody response. Low levels of rat BMC-binding IgM antibody were also detected in sera of tolerant mice, but the intensity of staining of rat BMC was lower than that of control animals receiving conditioning without BMT. These results suggest that a state of tolerance exists among cells responsible for T cell-dependent IgG antibody subclasses and natural IgM antibodies in animals receiving BMT following this nonmyeloablative conditioning regimen. PMID- 1585476 TI - Experimental graft arteriosclerosis. I. The Lewis-to-F-344 allograft model. AB - Progressive graft arteriosclerosis is responsible for the majority of late deaths occurring in cardiac transplant recipients. In order to define a model of this disease in the rat, we exchanged heterotopic cardiac allografts between MHC compatible inbred strains. Lewis rats served as donors and F-344 rats as recipients. Twenty allografts were followed by daily palpation and removed at the time of terminal rejection or on the 120th postoperative day for pathologic study. Sixteen allografts (80%) survived at least three weeks, and five allografts (25%) survived indefinitely. The majority of arteries (greater than 90%) examined demonstrated significant intimal disease; histologic findings in lesions in allografts rejecting at early time points included intense mononuclear cell infiltration of the intima, while lesions in long-term-surviving allografts demonstrated fibrous intimal thickening, which is characteristic of graft arteriosclerosis seen clinically. A limited course of cyclosporine therapy in F 344 recipients increased the incidence of indefinite allograft survival from 25% to 86%, and was associated with a modest reduction in the amount of intimal disease observed. These results suggest that this model should be useful in future studies regarding the pathogenesis and therapy of cardiac graft arteriosclerosis. PMID- 1585477 TI - Reversal of cirrhosis-related pulmonary shunting in two children by orthotopic liver transplantation. PMID- 1585478 TI - Matching for various HLA class II loci in cadaveric renal transplantation using DNA techniques. PMID- 1585479 TI - Orthotopic liver transplantation for type 1 Gaucher's disease. PMID- 1585480 TI - Cutaneous T cell lymphomas after renal transplantation. PMID- 1585481 TI - The rapid development of a fatal, disseminated B cell lymphoma following liver transplantation--serial changes in levels of soluble serum interleukin 2 and interleukin 4 (B cell growth factor). PMID- 1585482 TI - Cutaneous aspergillosis in a patient with orthotopic hepatic transplantation. PMID- 1585483 TI - HLA-mismatched cord-blood transplantation in a patient with advanced leukemia. PMID- 1585484 TI - The role of hemopoietic stem cells and accessory cells in tolerance induction. PMID- 1585485 TI - A simple procedure for large-scale density separation of bone marrow cells for transplantation. PMID- 1585486 TI - Management of the common duct in extended preservation of the liver. PMID- 1585487 TI - The biliary tree--the Achilles tendon of liver preservation? PMID- 1585488 TI - Liver transplantation after hepatic failure during pregnancy. PMID- 1585489 TI - Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies. PMID- 1585490 TI - Endothelial cell preservation using organ storage solutions. AB - The development of organ preservation solutions has been primarily accomplished in whole organ animal models. This study examines the toxicity of commonly used organ preservation solutions on endothelial cells in vitro. Primary human umbilical-vein endothelial cell cultures were incubated at 4 degrees C in solutions of 0.9% saline (NS), EuroCollins, ViaSpan (Belzer UW) (VIA), or Hank's balanced salts with 5% polyethylene glycol (PEG). Endothelial cell viability was ascertained by colormetric measurement of mitochondrial reduction of 3-(4,5 Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) to purple 1-(4,5 Dimethylthiazol-2-yl)-3,5-diphenylformazan. After exposure to hypothermic storage, cells were incubated at 37 degrees C in media with MTT, and the amount of reduced formazan present was quantified using a micro-ELISA spectrophotometer. Higher absorbance values were indicative of better cellular preservation. Cells stored in PEG displayed the highest viability at all time periods. ViaSpan provided better cellular protection than EC at longer storage intervals. This model allows for rapid assessment of preservation-induced endothelial cell injury and may aid development of improved storage techniques. PMID- 1585491 TI - Improvement of endothelial cell viability at 4 degrees C by addition of lazaroid U74500A to preservation solutions. AB - Lazaroids are potent inhibitors of lipid peroxidation. Endothelial cell damage has been shown to occur during cold storage preservation of lung and liver. This study examines the effects on endothelial cell viability of the addition of four lazaroids, U74006F, U78518F, U74500A, or U75412E to preservation solutions. Human umbilical vein endothelial cell cultures were stored at 4 degrees C for 48 and 96 hr in EuroCollins or 5% polyethylene glycol in buffered saline (PEG). U78518F, U74500A, U74006F, U75412E, or dexamethasone (each 50 microM) was added to EC (n = 32) or PEG (n = 32) and compared with control solutions of EC or PEG alone. Endothelial cell viability was determined by measuring cellular reduction of 3 [4,5-dimethylthiazol-2-yl]-2,3-diphenyltetrazolium bromide to a purple formazan dye. The reduction occurs only in viable cells and requires mitochondrial dehydrogenase activity. Results were quantified by measuring dye absorbance (Ab) with a micro-ELISA spectrophotometer. Absorbance values were compared by ANOVA and reported as mean values +/- standard deviation. Addition of U74500A to EC (Ab = 0.474 +/- 0.055) and PEG (Ab = 0.462 +/- .005) improved viability at 48 hr when compared with EC (Ab = 0.289 +/- 0.069) and PEG (Ab = 0.287 +/- 0.052) alone (P less than 0.05). At 96 hr, addition of U74500A resulted in improved viability in both EC (Ab = 0.377 +/- 0.068) and PEG (Ab = 0.195 +/- 0.09) or PEG alone (Ab = 0.212 +/- 0.1) (P less than 0.05). Other lazaroids tested were also effective in improving cellular viability, but to a lesser degree than U74500A. This study demonstrates that the addition of lazaroids to organ preservation solutions improves endothelial cell viability. PMID- 1585492 TI - The mechanism of action of the two-layer (Euro-Collins' solution/perfluorochemical) cold-storage method in canine pancreas preservation- the effect of 2,4 dinitrophenol on graft viability and adenosine triphosphate tissue concentration. AB - Tissue concentrations of adenosine triphosphate have been previously associated with successful pancreas preservation using the two-layer cold storage method in a canine autotransplantation model. To clarify the role of ATP vs. oxygenation per se, we used 2,4 dinitrophenol, an uncoupler of mitochondrial oxidative phosphorylation. DNP caused no toxicity in pancreas grafts preserved for 24 hr in Euro-Collins' solution or 48 hr in University of Wisconsin solution. Tissue concentration of ATP and viability of pancreas grafts, defined as maintenance of normoglycemia for 5 days following transplantation, were compared among six groups after a preservation interval of 24 or 48 hr. After 24 hr all grafts were viable, whether preserved using simple cold storage in EC (group 1a), two-layer (EC/perfluorochemical [PFC]) method (group 2a), or two-layer (EC+DNP/PFC) method (group 3a); respective graft survival was 4/4 (100%), 5/5 (100%), and 4/5 (80%); one of five dogs in group 3a died of a cause unrelated to the pancreas. ATP levels were higher in group 2a compared with group 1a (7.47 +/- 0.47 vs. 1.41 +/- 0.53 mumol/g dry weight, P less than 0.01) and lower in group 3a compared with group 2a (1.25 +/- 0.37 vs. 7.47 +/- 0.47, P less than 0.01). After 24 hr, we observed no difference in viability despite ATP concentration differences. However after 48 hr preservation, graft viability varied among the groups: 0/4 (0%), 4/4 (100%), and 0/3 (0%) in groups 1b, 2b, and 3b, respectively. ATP tissue concentration was again higher in group 2b after two-layer (EC/PFC) method preservation (7.91 +/- 1.21 vs. 1.21 +/- 0.31 mumol/g dry weight, P less than 0.01) compared with EC preservation (group 1b). DNP again caused a significant decrease in tissue ATP in group 3b (0.61 +/- 0.07 vs. 7.91 +/- 1.21, P less than 0.01). The two-layer (EC/PFC) method clearly protected pancreas viability, and inhibition of ATP production using DNP caused loss of viability in this model. We conclude that oxygenation of the pancreas during preservation by the two-layer method allows continued ATP production within the graft. Metabolic processes vital to cellular integrity can be maintained, which produces an extended period of preserved pancreatic viability. PMID- 1585493 TI - A prospective randomized trial between Euro-Collins and University of Wisconsin solutions as the initial flush in hepatic allograft procurement. AB - University of Wisconsin solution is currently recognized as the best solution for long-term organ preservation. It is recommended that UW solution be used as the in situ flush prior to organ explantation. The purpose of our study was to determine if hepatic allograft function was impaired by flushing the graft in situ with Euro-Collins and later flushing the graft ex vivo with UW solution, prior to cold storage. Fifty-six donors were randomly assigned to either an EC (n = 24) or UW (n = 32) in situ flush. The livers flushed with EC in situ were later flushed with 1 L of UW on the back table and stored in UW solution. Livers flushed with UW in vivo were similarly flushed and stored in UW on the back table. Concerning the donor allograft, there was no statistical difference (P greater than 0.05) between groups in sex, race, blood type, arterial anatomy, age, prothrombin time (PT), partial thromboplastin time (PTT), total bilirubin (TBR), direct bilirubin (DBR), aspartate amino transferase (AST), or alanine amino transferase (ALT). In addition, the recipients were compared for differences in sex, race, blood type, preoperative status, number of rejections, recipient age, length of surgery, and ischemia time and patient survival. There was no significant difference between groups (P greater than 0.05). There was no significant difference in patient survival (P = 0.238). Values for TBR, AST, ALT, PT, PTT, and AP were collected immediately preoperatively and postoperatively and on postoperative days 1, 3, 7, 14, and 28. There was no difference between groups in these values (P greater than 0.05). In our study there was no difference between the groups with respect to graft performance. This would justify the use of EC as an in situ flush during solid organ procurement and flushing with UW solution on the back table with an estimated savings of $400 to $1200 per procurement. PMID- 1585494 TI - The powerhouse of the cell. PMID- 1585495 TI - Giant mitochondria in "zero-hour" transplant biopsies. AB - Giant mitochondria in kidneys have increasingly been observed since the introduction of Cyclosporin A (CSA) as immunosuppressant in kidney transplants and in patients with autoimmune disorders. In animals treated with CSA, giant mitochondria were also described. In a study of "zero-hour" biopsies taken immediately before or after reperfusion of the renal transplant, giant mitochondria were often unexpectedly found. Retrospective analysis revealed that a significant increase in the number of giant mitochondria is more often associated with CSA therapy than ischemia. Giant mitochondria with sparse cristae seem to prevail in ischemia, whereas those with dense matrix and crystalloid structures predominate in CSA therapy. PMID- 1585496 TI - Hepatic ultrastructure in congenital total lipodystrophy with special reference to peroxisomes. AB - The liver of an 8-year-old boy with congenital total lipodystrophy was investigated by means of catalase cytochemistry and morphometry. Comparison was made with eight human control livers. Light microscopy revealed cirrhosis and steatosis. Ultrastructural changes included lipid droplets with lamellae in the periphery, cup-shaped mitochondria, and nuclear pseudoinclusions. Peroxisomes were significantly increased in number but were not enlarged; they displayed various shapes and showed a moderate heterogeneity in catalase activity. A correlation between increased lipids and peroxisomal proliferation is suggested. PMID- 1585497 TI - Colloid cyst of the third ventricle: a comparative ultrastructural study of neuraxis cysts and choroid plexus epithelium. AB - Thirteen colloid cysts (CC), four Rathke cleft cysts (RCC), three follicular cysts of normal pituitary gland (FCP), four enterogenous cysts (EC), three normal choroid plexi (CP), three choroid plexus papillomas (CPP), and several samples of normal bronchial mucosa and ependyma were studied by electron microscopy. The ultrastructure of most of the CC was indistinguishable from that of RCC, FCP, EC, and normal bronchial mucosa in demonstrating nonciliated and ciliated epithelial cells, goblet cells, basal cells, and intermediate forms, some showing evidence of early squamous differentiation. Two CC displayed mostly squamous differentiation, and one contained basally situated cells resembling myoepithelial cells. Although the RCC and FCP displayed features similar to those of CC, they also contained cells with electron-dense granules indicating pituitary hormone production and scattered cells showing oncocytic change. EC were lined by either squamous cells or mucin-producing columnar cells. Every CC, RCC, FCP, and EC contained cells covered by glycocalyx. In contrast to aforementioned lesions, ependymal lining, CP, and CPP were composed of a single cell type, one with numerous villi, few cilia, and no signs of keratinization, mucin production, or glycocalyx coating. It is concluded that the ultrastructural properties of CC are the same as those of cysts of endodermal or ectodermal origin and of respiratory mucosa. No ultrastructural similarities were observed between CC and normal or neoplastic neuroepithelium. These ultrastructural findings support the concept of an enterogenous origin of colloid cysts and highlight their similarity to RCC. PMID- 1585498 TI - The use of fixed-frozen tissue in routine ultrastructural evaluation and immunogold labeling. AB - A method of freezing fixed surgical tissue specimens for long-term storage and subsequent resin embedding was developed. The method entails fixation of the specimens in Karnowsky's liquid, cryoprotecting with 10% sucrose, freezing in melting Freon gas, and storage at -80 degrees C. When needed, even after years, the frozen tissue pieces are thawed in lukewarm (37 degrees C) buffer and embedded in resin (Epon or Lowicryl). Ultrastructural detail as well as immunocytochemical reactivity of a wide variety of cellular constituents are well preserved. The method is practical and allows retrospective embedding in Lowicryl resin (a technique not easily applicable in everyday routine) for subsequent ultrastructural immunolocalization studies. PMID- 1585499 TI - Electron microscopic analysis of myeloma cells in relation to drug response and prognosis. AB - Myeloma cells obtained from 33 patients were analyzed by electron microscopy to determine whether there is any correlation among ultrastructural characteristics of myeloma cells, drug response, and prognosis. The median survival time after diagnosis of responders (18 cases) and nonresponders (15 cases) was more than 423 days and 139 days, respectively. Nuclear immaturity and three cytoplasmic abnormalities--scattered pattern of mitochondria, single-sac looplike structures, and numerous intramitochondrial granules--were found to be associated with poor outcome. Although the cytoplasm of almost all the myeloma cells examined was judged to be mature or intermediate, the degree of nuclear immaturity was considered to correspond closely to the grade of nuclear-cytoplasmic asynchrony. Thus the electron microscopic examination of myeloma cells is of use to assess accurately their immaturity and abnormality and might provide clues for the prediction of drug response and prognosis of individual patients. PMID- 1585500 TI - Case for the panel. Clear spaces in aggregates of glycogen in a case of ewing sarcoma. PMID- 1585501 TI - Application of ultrasound to biotechnology: an overview. AB - Application of ultrasound to biotechnology is relatively new, but several processes that take place in the presence of cells or enzymes are activated by ultrasonic waves. High intensity ultrasonic waves break the cells and denaturize the enzymes. Low intensity ultrasonic waves can modify cellular metabolism or improve the mass transfer of reagents and products through the boundary layer or through the cellular wall and membrane. In the case of enzymes, the increase in the mass transfer rate of the reagents to the active site seems to be the most important factor. Immobilized enzymes are more resistant to thermal deactivation produced by ultrasound than native enzymes. Reverse micelles can be used to carry out synthesis using enzymes. Several applications of ultrasound to the biotechnology are discussed. PMID- 1585502 TI - Formation of bubbles in guinea-pig leg in vivo. PMID- 1585503 TI - Pacemaker activity of the pelvicalyceal border recorded by an intracellular glass microelectrode. AB - Applying intracellular glass microelectrodes to the smooth muscle obtained from the guinea pig pelvicalyceal border, we have succeeded in recording periodic spontaneous action potentials, the so-called slow waves, which are characteristic of a pacemaker. This experiment proved that the pacemaker exists at the pelvicalyceal border. The slow waves originate from the pelvicalyceal border, close to the papilla renalis; they show a biphasic pattern and have the characteristics of a spontaneously excitable cell. The resting potential is 42.3 +/- 1.1 mV, the spontaneous depolarizing potential is 12.1 +/- 0.7 mV, and the depolarizing period is 12/min. The rate of rise of the potential is 22.9 +/- 2.1 mV/s in the first slow depolarization phase, and 50.9 +/- 9.5 mV/s in the following rapid depolarization phase. The rate of decline of the potential is 47.3 +/- 5.4 mV/s in the repolarization phase. PMID- 1585504 TI - Normal growth with renal insufficiency owing to posterior urethral valves: value of long-term diversion. A twenty-year follow-up. AB - Twenty-five patients with posterior urethral valves have been monitored for 10-29 years (mean 18 years). Eight underwent diversion because of impaired renal function (creatinine greater than 0.8 mg/dl) accompanied by unimproved upper tract form and function after valve ablation. In the nondiverted group, 6 patients (35%) progressed to renal failure; in the diverted group 5 patients (63%) did so (p = 0.30). Of 13 patients whose lowest serum creatinine in the first year after valve ablation was greater than 0.8 mg/dl, 9 (69%) went on to renal failure (p = 0.02); in the remaining 12 patients, only 2 (17%) did so (p = 0.008). The mean age for renal failure was 13 years for both groups. The Tanner scale rating (mean percent height) for all patients at 10 years was 61% for the diverted group and 35% for those without diversion (p = 0.004). When the patients treated after the age of 1 year (n = 7) were excluded from the calculation, the rating remained different (54% diversion, 26% no diversion; p = 0.012). We conclude that the boy born with urethral valves and serious upper tract damage is at risk for renal failure, especially during the teen years. An undefined relationship appears to exist between urinary obstruction and growth. In our study, the boys who underwent diversion continued to grow along a normal Tanner height curve. PMID- 1585505 TI - Renal needle biopsy of the transplant kidney: vascular and urologic complications. AB - The authors reviewed the complications of 114 needle biopsies performed in 103 transplant kidneys. The diagnostic and therapeutic approach has changed markedly as a result of the introduction of Doppler ultrasound and the possibility of selectively embolizing fistula tracts. Macroscopic haematuria was the most frequent complication (5%); in one case it appeared 1 week after biopsy and was complicated with obstructive anuria due to a pyeloureteric clot. The incidence of arteriovenous fistulae was fairly low (0.9%); a selective renal angiography was performed, confirming the vascular lesion and allowing its selective embolization. Perirenal blood collections were also rare and the amounts were small. PMID- 1585506 TI - The use of ultrasonography as the initial diagnostic exploration in blunt renal trauma. AB - Fifty-four patients with blunt renal trauma underwent abdominal ultrasound as their initial diagnostic exploration if their hemodynamic status and associated injuries did not contraindicate unnecessary delays. Renal ultrasound allowed us to diagnose the injuries and to identify which patients required a more aggressive radiological exploration to obtain a diagnosis of certainty. At the same time we were able to certify that this technique is highly accurate in the diagnosis of lesions associated with gross hematuria. The noninvasiveness and low cost of this procedure makes it, in our experience, the technique of choice in the initial workup of blunt renal trauma. PMID- 1585507 TI - Cytogenetics of tumor cells from patients with nonfamilial renal cell carcinomas. AB - We analyzed cytogenetically 20 nonfamilial renal cell carcinomas, using a combined method of enzymatic technique and short-term culture with several passages. From 16 of the 20 patients, metaphase cells suitable for analysis were successfully obtained. Fourteen of the 16 patients demonstrated clonal chromosome aberrations which included missing Y chromosome in 8, gain of chromosome 7 in 7, an extra X chromosome in 4, translocation between chromosome 3 and other chromosomes in 4, deletion of the short arm of chromosome 3 in 2 and monosomy 3 in 2. Abnormalities of chromosome 7 and sex chromosomes were only numerical, and those are thought to be related to the neoplastic changes of various malignant tumors. Abnormalities of chromosome 3, however, were not only numerical but also structural, especially in the short arm, and those may be possibly associated with the genesis of renal cell carcinoma. PMID- 1585508 TI - Serum creatine kinase B subunit in patients with renal cell carcinoma. AB - We determined the serum levels of the creatine kinase B subunit (CK-B) by an enzyme immunoassay method in patients with renal cell carcinoma (RCC) and benign renal diseases. Eighteen of 76 patients with RCC (24%) had elevated serum CK-B levels. The positive rates were 29% in stage I, 13% in stage II, 15% in stage III, and 27% in stage IV. In all 9 patients whose serum CK-B levels were serially measured and had been elevated before operation, the CK-B levels were reduced to the normal range after nephrectomy. These findings indicate that serum CK-B is a useful biomarker for monitoring the clinical course for a limited number of RCC patients, but is not a marker for diagnosis and staging. Concentrations of CK-B in RCC tissues were significantly lower than those of normal kidney. A high rate of cell turnover in tumor tissues might entail the higher level of serum CK-B in patients with RCC. PMID- 1585509 TI - Lectins in diagnosis of bladder carcinoma. AB - With the purpose of studying changes in the expression of glycoconjugate structures in nonmalignant and cancerous lesions of urothelium the lectins ConA, TKA, PNA, DBA, STA, LFA, UEA, MPA, RCA, LCA, GSA1, SBA, GSA2, WGA, PHA and Lot were tested in formalin-fixed, paraffin-embedded tissue sections of (1) cold biopsies from normal urothelium and bladder cancer of different grades (G1-G3) in humans, (2) normal transitional epithelium and N-butyl-N(4 hydroxybutyl)nitrosamine (BBN)-induced bladder cancer in animal experiments (Wistar rat), and (3) human transitional cancer cell line HT 1376. In human urothelium TKA and SBA were positive markers demonstrating positive staining reactions in all tumor grades without binding to normal epithelium. They stained also the human transitional carcinoma cell line HT 1376 (G3). In Wistar rats DBA, ConA, LCA, SBA, GSA2 and WGA had a specific affinity to BBN-induced carcinoma. Findings of positive lectin marker in transitional cell cancer may offer progress in diagnostics and therapy. PMID- 1585510 TI - Mitomycin C in multiple superficial bladder tumors: short-term therapy, long-term results. AB - At the Institute of Urology, University of Padova, 125 patients with multifocal superficial bladder cancer underwent treatment with intravesical Mitomycin C (MMC; 1 weekly instillation of 40 mg for 8 consecutive weeks) between January 1982 and December 1988. Eighty-four patients had multifocal papillary tumors (stages Ta-T1) and 41 patients had carcinoma in situ of the bladder. At 6 and 36 months the tumor free percentage in the group with papillary tumors was 69 and 36%, respectively; for carcinoma in situ the complete response percentage at the same intervals was 80 and 36%. Thirty-one patients previously unsuccessfully treated with adriamycin did not show any difference compared to untreated ones. The authors emphasize the efficacy and low toxicity of intravesical MMC in multiple superficial bladder cancer. The possibility of long-term relapse suggests maintenance therapy. PMID- 1585511 TI - M-VAC versus CisCA--chemotherapy in the treatment of advanced bladder cancer. AB - The results of this study do not demonstrate a superiority of M-VAC chemotherapy over a modified CisCA regimen chemotherapy. M-VAC, however, proved less toxic than CisCA in terms of side effects. Neither CisCA nor M-VAC was effective as a curative treatment for patients with distant metastases. A durable complete remission of 22.5 months was seen in only 2 of the 12 patients with locally advanced tumors without distant metastases treated with M-VAC, and one of 35 months was observed in only 1 of the 6 cases with locally advanced tumors treated with CisCA chemotherapy. PMID- 1585512 TI - Local control of prostate cancer by intraarterial infusion chemotherapy facilitated by the use of angiotensin II. AB - Intraarterial infusion chemotherapy with angiotensin II was carried out in 8 prostate cancer patients whose ages ranged from 61 to 77 years. They had stage C or D tumor progression and complained of difficult urination, bone pain or lymphedema caused by intrapelvic tumor infiltration. Endocrine therapy had been done before the infusion therapy but the clinical status showed little change with a persistence of local symptoms. Cis-platinum and doxorubicin were infused with an indwelling catheter into both internal iliac arteries. After the completion of 1-5 courses, 6 of 8 patients responded remarkably in local symptoms. It is thought that intraarterial infusion chemotherapy can be used safely and effectively in elderly patients. PMID- 1585513 TI - Diffusion of cefmenoxime and latamoxef into prostatic fluid in the patients with acute bacterial prostatitis. AB - Twenty-two patients with acute bacterial prostatitis were treated with cefmenoxime (CMX) or latamoxef (LMOX), which have susceptibilities against various gram-negative bacteria. First 11 patients received a 5- to 12-day course of cefmenoxime and the next 11 received a 6- to 13-day course of latamoxef. All patients were treated successfully except 1 patient with a drug allergy. Diffusion of CMX or LMOX into prostatic fluid in these patients and healthy controls were evaluated. The mean value of CMX in the expressed prostatic fluid was 12.8 micrograms/ml in the patients receiving 2 g of CMX intravenously and 0.7 micrograms/ml in the controls. The mean value of LMOX was 14.0 micrograms/ml in the patients receiving 2 g of LMOX intravenously and 1.2 micrograms/ml in the controls. The diffusion of CMX and LMOX into prostatic fluid in the patients with acute bacterial prostatitis was strikingly higher than that of controls. PMID- 1585514 TI - Clinical significance of measurement of serum D-arabinitol levels in candiduria patients. AB - D-Arabinitol, a major candidal metabolite, is reported to be a useful parameter to diagnose disseminated candidiasis. Conventional determination of serum D arabinitol levels using gas-liquid chromatography is complicated and time consuming compared with the enzymatic fluorometric assay, newly available in kits. D-Arabinitol concentrations were determined by both enzymatic fluorometric assay kits and gas-liquid chromatography, and a significant correlation (r = 0.943, p less than 0.01) was found between the two methods in 25 sera from 15 patients with candiduria. D-Arabinitol/creatinine ratios were determined using the enzymatic fluorometric assay in 39 candiduria patients (21 febrile and 18 afebrile) and 22 patients without candiduria as the control. The ratios in the febrile patients were significantly greater than those in the afebrile and the nondocumented candidiasis groups. These results suggest that knowledge of the serum D-arabinitol concentration may help to promptly diagnose invasive candidiasis, particularly Candida pyelonephritis. In addition, enzymatic fluorometric assay kits are considered to be advantageous in that they require little time and are simple to use, as compared with gas-liquid chromatography. PMID- 1585515 TI - Experiences with extracorporeal shock wave lithotripsy in patients with a solitary kidney. AB - Between March 1985 and January 1990, 43 patients with stones in solitary kidneys were treated by extracorporeal shockwave lithotripsy (ESWL) in our department. The most common cause of unilateral kidney absence was previously surgical removal of the kidney. The primary treatment modality was ESWL in all patients; the need for auxiliary procedures was higher than in general stone patients. Of the 43 patients 42 were available for control checkups after therapy, and these examinations revealed a stone-free rate of 85.7%. Of the patients 14.3% had asymptomatic lower calix fragments. All our patients showed a successful result 6 months after ESWL therapy. No loss of kidney was observed. Our results indicate that ESWL as an effective and safe method is also the therapy of choice for stone patients with solitary kidneys. PMID- 1585516 TI - Influence of morphologic factors on calcium-containing stone formation. AB - Pathogenesis of urolithiasis cannot be explained only by metabolic disorder. In the present study, morphologic differences of the renal pelvic-caliceal system (PCS) were examined on both the stone and normal sides in calcium-containing stone formers. The results indicated that as compared to the normal side, the urine flow in the PCS was stagnant or not straight on the stone side even in the same individual, showing unfavorable conditions for stone formation. It is therefore considered that morphologic disorders of the urinary tract may be one of the causes for stone formation. PMID- 1585517 TI - Transurethral treatment of bladder diverticulum. AB - Transurethral resection of the bladder diverticular neck and fulguration of the diverticular mucosa were performed in 31 diverticula. Cystograms showed that 26 of the 31 diverticula had disappeared completely after 1 month. Follow-up cystograms have shown no recurrence, and no further surgical procedures were required. Therefore, we conclude that resection of the diverticular neck from 4 to 8 o'clock to even the gap between the bladder mucosa and diverticular wall in conjunction with transurethral treatment of the prostate, if required, is a safe, fast and effective method. PMID- 1585518 TI - Construction of a continent catheterizable urinary valve from a gastric segment in dogs. AB - We constructed a continent, catheterizable urinary valve from a gastric segment in 7 dogs. A vascularized gastric segment was isolated from the greater curvature and was tubularized. A cuff was made at the distal end of the tube. The gastric tube was anastomosed to the dome of the bladder with intussusception of the cuff portion into the bladder cavity. The valve provided continence over a wide range of bladder pressure. However, an ulcer of the bladder developed where the gastric mucosa of the cuff faced the bladder mucosa in 5 dogs, with a resultant intraperitoneal perforation in 2 dogs. The development of the bladder ulcer may be a serious complication of an anastomosis of an isolated gastric segment to the bladder. PMID- 1585519 TI - Ureteral triplication with contralateral ureter duplication. AB - A rare case of ureteral triplication with contralateral duplication is reported. The incidence, embryology, classification and symptomatology are commented. The most relevant literature is reviewed. PMID- 1585520 TI - Conflicting aspects of renal leiomyoma with different imaging techniques. AB - A case with benign renal leiomyoma examined by all the imaging techniques currently available is described. The aspects were conflicting, particularly with regard to sonography and magnetic resonance imaging, and the sole technique which provided more reliable information was the CT scan. PMID- 1585521 TI - Liposarcoma of the renal capsule. AB - We report a case of liposarcoma of the renal capsule. The literature is reviewed, and diagnosis and management are discussed. PMID- 1585522 TI - Primary localized amyloidosis of the bladder: a case of AL (lambda) amyloid protein and combination therapy using dimethyl sulfoxide and cepharanthin. AB - We report a case of primary localized amyloidosis of the bladder with amyloid deposits which was characterized as being of immunoglobulin light chain origin (AL) including lambda type (A lambda) and P component (AP) using the KMnO4 pretreatment method and immunohistochemical procedures. The patient was treated successfully with intravesical dimethyl sulfoxide instillation and oral administration of high-dose cepharanthin after transurethral resection. Combination therapy with dimethyl sulfoxide and cepharanthin was shown to be useful for primary localized amyloidosis of the bladder. PMID- 1585523 TI - Pheochromocytoma of the urinary bladder. AB - A case of a pheochromocytoma of the urinary bladder is reported which was treated preoperatively with alpha-receptor-blocking agents. The tumor was operated transurethrally, followed by partial cystectomy. PMID- 1585524 TI - 45,X/46,XY gonadal dysgenesis in an infertile adult male. AB - A 33-year-old male was referred for infertility. Examination revealed bilateral scrotal gonads of soft consistency and small size. Semen analysis showed azoospermia. Elevated serum follicle-stimulating hormone levels and normal testosterone values were found. Surgical exploration and histopathology diagnosed dysgenetic testes with complete epididymis, and remnants of Fallopian tubes attached to the albuginea, with normal vas deferens and seminal vesicles showed on deferentovesiculography. Karyotype was 45,X/46,XY del(Y)(q11) with only 15% of 46XY cells in gonadal tissue. The clinical spectrum of 45,X/46,XY mosaicism and significance of this chromosomic anomaly is discussed. PMID- 1585525 TI - Urological manifestations of acute appendicitis: report of two new cases. AB - Clinical manifestations of acute appendicitis are variegated and urologic symptoms may be the first manifestation of the disease. In 1985 we reported on 2 cases of acute appendicitis who presented with irritative bladder symptoms. Here we describe 2 new cases come to our observation because of hematuria and irritative bladder symptoms. A brief review of the literature is also carried out. PMID- 1585526 TI - [Method of iris retraction in narrow-angle glaucoma]. AB - A new surgical method for the treatment of narrow-angle glaucoma is suggested, consisting in the following: in sinuso-trabeculectomy the bridge cut from the deep layers of the sclera via a diagonal incision is transformed into triangular flaps that are charged into the anterior chamber for the iris retraction. The new geometry of incisions improves the efficacy of iris retraction and makes the surgery less traumatic. PMID- 1585527 TI - [Results of the use of betoptik (betaxolol) in the treatment of primary glaucoma]. AB - Effect of instillations of 0.5% betaxolol solution (Alcon) on intraocular pressure, ocular hydro- and hemodynamics, function, systemic arterial pressure, and pulse was studied in 35 patients (57 eyes) with primary open-angle glaucoma. The effects of betoptic and arutimol on the eyes are compared. Betoptic is characterized by a marked hypotensive effect explained by depression of aqueous humor production. The drug does not influence ocular function and hemodynamics. Comparison of the hypotensive effects of betaxolol and arutimol has shown that arutimol more effectively reduces intraocular pressure. PMID- 1585528 TI - [Emoxipine in the treatment of primary glaucoma]. PMID- 1585529 TI - [Visual evoked potentials in children with congenital glaucoma]. AB - Phasic and established visual evoked potentials (VEP) to homogeneous light field and chess patterns were studied in 25 patients (48 eyes) aged 1.5 months to 9 years with different stages of congenital glaucoma and in 114 age-matched healthy children. Patients with almost absolute and far progressed stages of the disease presented with gross changes of VEP to both large- and small-cell chess patterns. In patients with the initial stages of decompensated congenital glaucoma VEP to mostly large-cell chess patterns were altered. These data evidence the usefulness of examining the VEP to stimuli with low spatial frequency for the early detection of congenital glaucoma. PMID- 1585530 TI - [Intraocular correction in the restorative therapy of children with congenital and traumatic cataracts]. AB - A total of 140 surgeries making use of aspiration irrigation technique were carried out in 105 children with congenital and traumatic cataracts, aged 4 to 14. The Fyodorov-Zakharov iris clips lenses were implanted. The method was found highly effective and low traumatic. Grave complications, such as iridocyclitis, secondary glaucoma, macular edema, retinal detachment were recorded in late period in just few children, in 0.7-5% of cases. Vision acuity of at least 0.3 diopters was achieved in 87.1% of children with congenital and in 85.7% of those with traumatic cataracts. Binocular vision was restored in 81.4 and 83.3%, respectively. PMID- 1585531 TI - [Laser therapy in the treatment of complications of radiotherapy of the eyelids in children]. PMID- 1585532 TI - [A modified method of surgical treatment of blepharoptosis]. PMID- 1585533 TI - [Results of the use of a modified diploptic method for recovery of bifixation reflex in the treatment of concomitant strabismus in children]. AB - Exercises with changing distance between the eye and the test object, modified by the author, were used in the treatment of 75 children with strabismus after orthotropia was detected in them, in order to restore normal binocular vision that may be preserved if examined from various distances. After the treatment the frequency of recovered binocular vision at long and short distances was found the same. PMID- 1585534 TI - [Ergonomic evaluation of the effectiveness of the use of television and optic magnifiers for reading by the weak-sighted]. AB - The author analyzes the results of examinations of visual working abilities of 64 poor-sighted children making use of different correction means in reading and compare the data obtained in reading with optic and television amplifiers before and after 15 min reading a text written in standard type. The findings evidence that the work (reading) induced significant functional disorders both in the sensory and motor components of the visual system; in patients with vision acuity of 0.1 or higher vision fatigue was lower if an optic correction means was employed, and in patients with vision acuity below 0.1 diopters the fatigue was lower if a television amplifier was employed. Recommendations on improvement of television devices for reading and employment of various correction means for poor-sighted subjects are given. PMID- 1585535 TI - [Ring-like figures in the fundus oculi detected by ophthalmoscopy in transformed light]. AB - Examinations of the fundus oculi in red-free polarized light, carried out in 19 patients (12 with albinism and 7 with the albinotic type of the fundus oculi) have revealed for the first time a peculiar ring-like figure. Since there is no evidence that this figure is formed by retinal folds, the authors suppose that it may result from light wave interference. Light waves on the fundus oculi of albinos may be reflected not only by the internal border membrane, but by Bruch's membrane or sclera as well. These waves, overlapping each other, form a figure identical to Newton's interference rings. The presence of a ring-like figure in the centre of the fundus oculi may be regarded as an additional clinical sign of albinism of the fundus oculi. Together with other signs, this phenomenon may be used as a marker of albinism gene carriership. PMID- 1585536 TI - [Possibilities of computer-assisted processing of the results of an examination of the visual system]. AB - The authors present the first results of examining the vision system with the use of an automated programmed complex realized in the 'C' program language in the IBM and Dos operation system, that helped present in a chart the distribution of the ocular light sensitivity and time of the sensomotor reaction in every site of the visual field of 40-50 degrees. The results evidence that computer-aided methods may be effectively used to assess the light sensitivity of the eye, contrast sensitivity, space summation, rod and cone interactions, the topography of color photoreceptors, and the function of the posterior section of the eye in abnormalities of the retina and the optic nerve, as well as to monitor visual function rehabilitation after treatment. PMID- 1585537 TI - [Current problems of optic correction]. PMID- 1585538 TI - [Possibilities of the use of visual evoked potentials in the evaluation of visual acuity in congenital myopia in children]. AB - Studies of visual evoked potentials (EP) to chess field reversion in 80 children (147 eyes) aged 5 to 16 with congenital myopia have demonstrated significant deviations from the reference values of the P100 component to all the stimuli. The clinical groups with various changes in the fundus oculi were found to differ by the P100 component amplitude when chess fields with cells 112 and 56 angular min in size were shown. The number of discrepancies between the clinical vision acuity and its assessment from the threshold EP grew from 19% when no changes in the fundus oculi were seen to 54 and 61% when myopic and non-myopic changes were detectable in the fundus oculi. These data evidence that EP amplitude to chess field reversion better reflects the status of the retino-cortical route than the central vision acuity. PMID- 1585539 TI - [Neuro-ophthalmological examinations in craniopharyngiomas in childhood]. AB - The results of ophthalmologic examinations of 50 children with craniopharyngiomas are analyzed. The condition was diagnosed on the basis of clinical examinations, roentgenography, angiography, brain scintigraphy, and computer-aided tomography. In 48 cases the diagnosis was confirmed by histologic findings. The mean age of the patients was 9 years 6 months, both boys and girls were included in the study group. Vision acuity deterioration was detected in 69.6% of children, optic disk edema in 22% and atrophic changes of the disk in 52% of the examinees. Vision field defects were revealed in 67.7%, nystagmus in 4 cases, oculomotor nerve paresis in 6 cases. The authors emphasize timely employment of conventional and present-day x-ray examinations, that are highly informative in such conditions, in all the patients with vision disorders of unknown origin and with suspected compression of the visual routes. PMID- 1585540 TI - [Formation of radiation and involution cataracts in man exposed to radiation]. AB - An ophthalmologic follow-up of subjects exposed to chronic total external gamma irradiation (747 subjects) and to gamma-neutron irradiation (1083 subjects) in total doses of 1 to 10 Gy has revealed no cases of radiation involvement of the eyes. Besides, a group of 8 patients with a history of acute radiation sickness were followed up, who were exposed to external gamma-neutron irradiation in total doses of 4 to 9.8 Gy. All these patients developed radiation burns of the skin of the face and eyelids, eyelashes and eyebrows epilation, 6 of these radiation cataracts and 2 mixed-type cataracts (radiation involutional ones). Radiation cataracts were developing within 10-32 months (the first stage). A forty-years' follow-up of the formation of radiation and involution cataracts permitted the authors single out the pathogenetic differences between these types and use these data for the solution of expert evaluation problems and problems related to social protection of people with acute radiation injuries of the eyes. The authors' results and the literature data evidence that, with due consideration for the irradiation dose and the patient's age, one can predict the type of a would-be cataract, periods of its formation and progress, and the treatment strategy. PMID- 1585541 TI - [A rare case of corneal dysgenesis]. AB - The authors report a rare case: corneal dermoid in a three-year-old boy. Etiologically the case may be explained by embryopathy. The prognosis was bad, therefore the eye had to be enucleated and a movable prosthesis was implanted, and thus a very good cosmetic effect achieved. Histologic study has revealed vast dysgenesis of the cornea. PMID- 1585542 TI - [Drug-induced lesions of the organ of vision (review)]. PMID- 1585543 TI - [Trabeculodialysis]. AB - Trabeculodialysis, a new antiglaucoma surgical technique, developed at the Chair for Ophthalmic Diseases of the Yaroslavl Medical Institute, is described. Trabeculodialysis is aimed at recovery of intraocular fluid discharge via Schlemm's channel and then through orifices into intra- and episcleral vessels; this technique is indicated for patients with open-angle glaucoma in trabecular form of retention. Since 1990 this operation was performed in 50 glaucoma patients. The results will be presented in another paper. PMID- 1585544 TI - Opinions in small animal anesthesia. PMID- 1585545 TI - Injectable anesthetics. PMID- 1585546 TI - Advantages and guidelines for using ultrashort barbiturates for induction of anesthesia. AB - Despite the introduction of a number of new injectable agents, ultrashort barbiturates continue to be popular. Some of the reasons include rapid, smooth onset of action; predictable hypnotic effects; relatively rapid, smooth recovery; and inexpensiveness. Ultrashort barbiturates also possess some pharmacodynamic properties that make them ideal agents for use in patients with certain diseases or undergoing certain procedures. These include patients with raised intracranial pressure, patients with a history of seizures, patients with corneal lacerations or glaucoma, patients for examination of vocal cord and arytenoid cartilage function, patients with hyperthyroidism, and patients thought to be susceptible to malignant hyperthermia. PMID- 1585547 TI - Precautions when using ultrashort thiobarbiturates for induction of anesthesia. PMID- 1585548 TI - Advantages and guidelines for using ketamine for induction of anesthesia. AB - Ketamine in combination with a sedative or tranquilizer is a relatively safe and effective drug for intravenous induction of anesthesia in dogs and cats. If properly dosed, the combination can be used to induce anesthesia with minimal adverse cardiovascular effects, and it is a reasonable method for induction of anesthesia in patients with cardiac disease. If dosage is kept low, the rate of recovery is acceptable, and some of the drugs commonly used in the regimen with ketamine are reversible with appropriate antagonists. PMID- 1585549 TI - Precautions when using ketamine for induction of anesthesia. PMID- 1585550 TI - Advantages and guidelines for using opioid agonists for induction of anesthesia. AB - Opioids have a central role in the anesthetic management of small animals, as premedicants, as part of a balanced anesthetic technique, or for the provision of postoperative analgesia. These drugs are safe to use, provide excellent analgesia, and are easily reversible. They cause minimal cardiovascular depression and induce no deleterious renal or hepatic changes. These agents, combined with a sedative, generally provide an ideal anesthetic state. PMID- 1585551 TI - Precautions when using opioid agonists for induction of anesthesia. AB - Opioids produce unpredictable anesthesia that is associated with poor muscle relaxation, prolonged onset, and relatively difficult intubation. They often induce bradycardia, which must be countered with atropine or glycopyrrolate, and hypoventilation, which requires ventilatory support. Return to consciousness is often delayed, making postoperative assessment of the patient's condition difficult. Finally opioid induction is relatively expensive compared with other anesthetic induction regimens. PMID- 1585552 TI - The case for maintenance of general anesthesia with an injectable agent. AB - The maintenance of anesthesia with injectable drugs provides a safe alternative to inhalant techniques, provided that the basic needs of the patient are met. The standard drugs (e.g., thiobarbiturates, methohexital, ketamine) can be used, economically and safely, to provide a short duration of anesthesia, but the best drugs for more prolonged procedures are more expensive (e.g., alfentanil, fentanyl, propofol) and require more sophisticated equipment to provide optimal conditions. PMID- 1585553 TI - Advantages of etomidate use as an anesthetic agent. AB - Etomidate is a useful addition to the list of available anesthetic agents. When faced with an animal with cardiovascular instability, cirrhosis, an intracranial lesion, susceptibility to malignant hyperthermia, anaphylactoid tendencies, or one that requires cesarean section, one should consider using etomidate. In addition, it provides a safe method for total intravenous anesthesia in situations in which the nature of the surgery precludes the use of an endotracheal tube, when the use of an inhalant is undesirable for any reason, or when inhalant anesthetic equipment is unavailable. PMID- 1585554 TI - Precautions when using etomidate in veterinary medicine. PMID- 1585555 TI - Other potentially useful new injectable anesthetic agents. AB - Ultrashort barbiturates are not ideal injectable anesthetic agents, and new agents continue to be released as investigators pursue the goal of finding a more ideal agent. Of the new injectable agents discussed, propofol seems to be the most promising drug. Propofol should find a place in veterinary practice as an outpatient anesthetic agent because it has a rapid, smooth, and complete recovery even after repeated or continuous administration. Midazolam does not induce anesthesia in healthy, small animals and, as such, can only be used in combination with other injectable agents, such as ketamine or the thiobarbiturates. In our practice, Telazol has found a place in the anesthetic management of feral cats and aggressive dogs, where it is used for heavy sedation or to induce anesthesia. The role of flumazenil, as a reversal agent, in veterinary practice remains to be determined; however, the role in small domestic animals is unlikely to be significant. PMID- 1585556 TI - Inhalational anesthetics. PMID- 1585557 TI - Advantages and guidelines for mask induction. AB - Inhalational agents with low blood/gas solubilities (halothane, isoflurane, and nitrous oxide) are preferred for mask induction. A gradual step up in the vaporizer concentration is the recommended induction method because it is generally smoother and safer than the crash induction technique. PMID- 1585558 TI - Precautions when using mask induction. AB - There are few techniques as frequently employed in veterinary anesthesia that are more dependent on good clinical judgment, technical skill, and finesse than mask induction. The technique can be extremely valuable in selected patients. PMID- 1585559 TI - The case for maintenance of general anesthesia with an inhalational agent. AB - Control of anesthetic depth is the primary advantage of general anesthesia with inhalational anesthetics as opposed to injectable agents. In addition, inhalational anesthetics provide good intraoperative stress reduction, adequate muscle relaxation, and an elimination pathway (lungs) independent of liver and kidney function. There is little postoperative respiratory depression and no rebound effect, which is sometimes seen with injectable anesthetics. The incidence of anesthetic-related toxicity is rare and is not considered a problem. PMID- 1585560 TI - Advantages and guidelines for using nitrous oxide. AB - Nitrous oxide is useful as an adjunct to methoxyflurane anesthesia and prolonged halothane anesthesia. Nitrous oxide is also useful in the debilitated patient in which the potent volatile anesthetics induce excessive cardiovascular depression. Finally nitrous oxide is useful for smoothing an inadequate anesthetic plane induced by the potent volatile anesthetics. PMID- 1585561 TI - Precautions when using nitrous oxide. PMID- 1585562 TI - Advantages and guidelines for using methoxyflurane. AB - Methoxyflurane anesthesia is particularly useful for orthopedic surgery (muscle relaxation, analgesia, and slow recovery), ophthalmic surgery (central eye position), and small laboratory animals (high therapeutic index and slow induction). PMID- 1585563 TI - Precautions when using methoxyflurane. AB - Methoxyflurane has a high blood/gas partition coefficient and a low vapor pressure. Mask inductions may be excessively slow, necessitating early high vaporizer control knob settings or additional injectable induction agent. Recoveries may be very prolonged. Methoxyflurane is extensively metabolized, and this may be associated with hepatotoxicity and nephrotoxicity. PMID- 1585564 TI - Advantages and guidelines for using halothane. AB - Halothane is a frequently used agent. Its cost is inexpensive. Halothane is a safe and effective anesthetic agent if used properly. Proper usage includes adjusting the concentration administered to produce adequate anesthesia for the procedure without excess depression of cardiac, respiratory, and neurologic function. Proper monitoring of the patient indicates the adjustments needed in concentration or needed medications or procedures to increase safe usage. Potent tranquilizers, sedatives, and analgesics used as preanesthetics during halothane anesthesia or the early postanesthetic period may produce profound changes in anesthetic concentrations required or physiologic responses to the combined medications. PMID- 1585565 TI - Precautions when using halothane. AB - Halothane is a potent inhaled anesthetic that is used extensively in veterinary practice. Certain properties and side effects warrant careful monitoring of patients anesthetized with it and may preclude its use in certain individuals. PMID- 1585566 TI - Advantages and guidelines for using enflurane. PMID- 1585567 TI - Precautions when using enflurane. AB - Enflurane offers few advantages over halothane, and it is more expensive than halothane. It causes greater cardiopulmonary depression and induces seizure activity. When economy and systemic effects are considered, enflurane offers no real benefits for veterinary anesthesia. PMID- 1585568 TI - Advantages and guidelines for using isoflurane. AB - Isoflurane offers many advantages over other inhalational anesthetics. Its faster induction and recovery, relative sparing effect on cardiovascular function and cerebral blood flow autoregulation, and negligible metabolism make this drug particularly useful in the anesthetic management of the debilitated, aged, or unusual veterinary patient. PMID- 1585569 TI - Precautions when using isoflurane. PMID- 1585570 TI - Other new and potentially useful inhalational anesthetics. AB - Sevoflurane and desflurane are volatile inhaled anesthetics that are currently being investigated as possible improvements for the anesthetic management of human patients. Information to date suggests these agents have several advantages over existing clinical agents. For example, the blood/gas partition coefficient for both agents is lower than that of other halogenated anesthetics. Consistent with this physical characteristic is a more rapid induction of and emergence from anesthesia. Both cause a dose-related depression of cardiopulmonary function, which is comparable to isoflurane. Results of studies to date favor desflurane over sevoflurane because it is less soluble in blood, is stable in soda lime, is biodegraded the least of any volatile anesthetic, and is not toxic. PMID- 1585571 TI - Advantages of and guidelines for using neuromuscular blocking agents. AB - Neuromuscular blocking agents, although not commonly used in veterinary practice, should be considered when muscle relaxation is needed to facilitate surgical exposure and minimize tissue trauma. These drugs should be administered only once respiration has been controlled and anesthetic agents have been administered to induce unconsciousness and analgesia. Following administration of neuromuscular blocking drugs, neuromuscular and cardiovascular function must be monitored. PMID- 1585572 TI - Disadvantages of neuromuscular blocking agents. AB - Neuromuscular blocking agents have few indications and significant contraindications or problems associated with their use. The need for controlled ventilation and the difficulties of monitoring anesthetic depth when using neuromuscular blocking agents are overriding factors that mitigate against their routine use. PMID- 1585573 TI - Postoperative analgesia. PMID- 1585574 TI - The case for the routine use of analgesics. AB - Surgery is painful and it behooves us, as people who care for and take care of animals, to prevent their suffering whenever possible. Recent developments in the understanding of nociceptive physiology underscores this prospective, rather than retrospective, approach to the management of pain. We have the armamentarium to do this and there are very few deleterious side effects when appropriate treatments are used. PMID- 1585575 TI - The case against the routine use of analgesics. PMID- 1585576 TI - Advantages and guidelines for using agonist opioid analgesics. PMID- 1585577 TI - Precautions when using opioid agonist analgesics. AB - Opioid agonist analgesics are effective drugs for treating postoperative pain. Contraindications for their use are primarily respiratory depression and increased intracranial pressure. Their use may mask potentially serious postoperative complications. PMID- 1585578 TI - Advantages and guidelines for using opioid agonist-antagonist analgesics. AB - The opioid agonist-antagonists are not controlled substances requiring strict record keeping and security because of their low abuse potential. They are effective analgesics in their own right and can be used to antagonize opioid agonist-induced depression while retaining a degree of analgesia. Respiratory depression is less than that induced by opioid agonists, but degree of analgesia is somewhat limited also owing to the ceiling effect. PMID- 1585580 TI - Advantages and guidelines for using antiprostaglandins. PMID- 1585579 TI - Precautions when using opioid agonist-antagonist analgesics. AB - Agonist-antagonists are attractive because of their availability and absence of strict regulation. They do provide effective analgesia in many cases, and they are cost-effective. Incomplete analgesia can be noted in moderate to severe pain. Cardiopulmonary depression may be noted following agonist-antagonist administration. Interference with coadministered opiate agents may occur. PMID- 1585581 TI - Precautions when using antiprostaglandins. AB - Antiprostaglandins are effective for relief of pain of low to moderate intensity. The majority of these agents interfere with clotting function, and they should not be used on animals with potential coagulopathies. With high dosage or long term treatment, gastrointestinal irritation and ulceration are probable. NSAIDs should not be used in conjunction with methoxyflurane because of the potential for renal damage. Care should be taken to avoid hypotension with any anesthetic to obviate renal complications. PMID- 1585582 TI - The case for low gas flows. AB - When nitrous oxide is not used, there are no clinically significant, valid reasons for not using low gas flows. There are many clinically significant, valid reasons for using low flows. PMID- 1585583 TI - Vaporizer position. AB - The vaporizers that are positioned outside of the circle have known constant output concentrations and are not affected by positive pressure ventilation. The vaporizers that are positioned inside the circle system have unknown, variable output concentrations and are markedly affected by positive pressure ventilation. Either type can be safely used if its operating characteristics are understood. PMID- 1585584 TI - The case for in circuit vaporizers. AB - In circuit vaporizers have some characteristics that differ from out of circuit vaporizers. In circuit vaporizers are easy to use, effective, and offer several clinical advantages. PMID- 1585585 TI - The case for out of circuit vaporizers. AB - Out of circuit vaporizers have some characteristics that differ from in circuit vaporizers. When these are understood, out of circuit vaporizers offer some advantages. PMID- 1585586 TI - The case for rebreathing circuits for very small animals. AB - The objections to using adult circle systems on very small patients include increased resistance to breathing, mechanical dead space, and slow equilibration times. These objections warrant consideration before assuming that nonrebreathing systems have an inherent advantage for patients between 3 and 10 kg. The cost of anesthesia and the time taken to establish a desired anesthetic level are as important in determining which system to use for small animal patients. Based on the current evidence, it is acceptable to use adult circle rebreathing systems on healthy patients as small as 3 kg. PMID- 1585588 TI - The case for quantitative anesthesia. PMID- 1585587 TI - Quantitative anesthesia. AB - Quantitative anesthesia is delivering anesthetic and oxygen in known quantities, the dosage based on calculations for their uptake. The uptake is not linearly related to body weight but is linearly related to body weight raised to a power. The dosage of inhaled anesthetics is calculated by the method of Lowe. The oxygen consumption and cardiac output are estimated by formulas that relate physiologic functions to the body weight in kilograms, raised to a power. PMID- 1585589 TI - The case for qualitative anesthesia. AB - Qualitative anesthesia is an effective, time-honored, familiar, and simple technique for maintaining general anesthesia. There is no reason to change. PMID- 1585590 TI - Lumbosacral epidural management. AB - Spinal techniques (epidural and subarachnoid injection) are taught in veterinary curricula, but because they are less convenient they are not used widely in practice. Many animals undergoing routine (below the umbilicus level) surgical procedures can be anesthetized with mild sedation and caudal epidural analgesia. Ninety minutes of analgesia is provided by the shorter-acting agents, whereas bupivacaine provides 4 to 6 hours. Twelve percent of our attempts failed to produce analgesia. Sedation, surgeon acceptance, and patient temperament contributed to an additional few failures. High-risk cases are better handled on oxygen. PMID- 1585591 TI - Problems and precautions when using epidural analgesia for surgery. PMID- 1585592 TI - Advantages and guidelines for using epidural drugs for analgesia. AB - The administration of drugs by the epidural route is a safe and effective method for providing analgesia before, during, and after a surgical procedure. Local anesthetics administered by this route block nociceptive input as well as providing excellent muscle relaxation for surgery. The use of local anesthetics may be associated with short-term motor dysfunction and hypotension as a result of sympathetic blockade. Morphine given by the epidural route also provides effective analgesia and has the advantages of giving more prolonged analgesia with no effect on either motor or sympathetic pathways. PMID- 1585593 TI - Monitoring the anesthetized patient. PMID- 1585594 TI - General guidelines for judging anesthetic depth. PMID- 1585595 TI - Anesthetic depth: the undefinable. AB - With many modern anesthetic drugs and combinations, the traditional signs of anesthetic depth as a continuum of increasing depression are often incorrect. The concept of "adequate anesthetic depth" is difficult to define because it depends on the end points chosen to define "adequate." Because both central nervous system excitant and depressant drugs can induce a stage of anesthesia, it is vital that those using these agents be keenly aware of the specific type of anesthetic agent or agents being used, and their effects. PMID- 1585596 TI - The case for routine intraoperative ECG monitoring. AB - Monitoring of the ECG is not advocated as the sole means of assessing cardiovascular function, but it does play an essential role in the diagnosis of intraoperative arrhythmias and does alert the anesthesiologist to potentially serious problems, which may otherwise go unrecognized. PMID- 1585597 TI - The case against intraoperative ECG monitoring. AB - It can be seen that ECG monitoring has its limitations; however, if it is employed correctly, it can be an invaluable adjunct to physical monitoring. The ECG does not provide information about the cardiac contractile state or hemodynamic status and may not always permit the facile resolution of dysrhythmias; however, in conjunction with other forms of cardiovascular monitoring, the ECG permits the anesthetist to have greater confidence in cardiovascular events occurring during anesthesia and permits the early detection and treatment of cardiac rhythm disturbances. PMID- 1585598 TI - What blood pressure monitoring doesn't indicate. PMID- 1585599 TI - The case for routine fluid administration. AB - Because the risks associated with fluid administration are small, but the effects of fluid withdrawal during anesthesia can be significant, routine fluids should be considered in all cases in which general anesthesia exceeds 45 minutes. PMID- 1585600 TI - The case against routine fluid administration. AB - The case for fluid administration in healthy patients anesthetized for elective procedures has been overstated. Compromised patients or patients undergoing extensive surgery benefit from the administration of intravenous fluids. PMID- 1585601 TI - Anesthesia for severe upper airway obstruction. PMID- 1585602 TI - Anesthesia for patients with preexisting pneumonia and cyanosis. PMID- 1585603 TI - Anesthesia for patients with diaphragmatic hernia and severe dyspnea. AB - Problems facing a patient with severe dyspnea secondary to diaphragmatic herniation are hypoxia, hypercarbia and respiratory acidosis, and cardiovascular instability. It is easy to precipitate a crisis in these patients during anesthetic induction as a result of stress, bad positioning, induction of pneumothorax, or inappropriate anesthetic technique. These patients require a smooth, stress-free perianesthetic period with preoxygenation, positioning with the affected side down, rapid intravenous induction, endotracheal intubation, and mechanical ventilation. Maintenance with isoflurane is preferred, and nitrous oxide should be avoided. Close monitoring of the cardiovascular and pulmonary systems is essential. Recovery from anesthesia should include oxygen supplementation, pleural drainage, and local analgesia if required. PMID- 1585604 TI - Anesthetic concerns for patients with cardiomyopathy. AB - Hypertrophic cardiomyopathy usually affects cats. The overall cardiac dysfunction associated with hypertrophic cardiomyopathy relates to a decrease in diastolic function. Anesthetic regimens that minimize increases in heart rate and stress related catecholamine release are desirable. Patients with dilative cardiomyopathy can present asymptomatic or in congestive heart failure. The overall myocardial defect is a depression of systolic function. An anesthetic regimen that minimizes myocardial depression is essential. PMID- 1585605 TI - Anesthesia for severe mitral and tricuspid regurgitation. AB - Anesthesia for mitral or tricuspid regurgitation should be designed to maintain cardiac output by decreasing systemic and pulmonary vascular resistance to aortic and pulmonary outflow, respectively, and by carefully preserving venous return. A moderate increase in heart rate may be helpful with mitral regurgitation; bradycardia should be avoided. Isoflurane, halothane, or opioid anesthesia is preferred. PMID- 1585606 TI - Anesthesia for very old patients. PMID- 1585607 TI - Anesthesia for patients with stable end-stage renal disease. AB - Patients with stable, end-state renal disease should be premedicated with an opioid and induced with minimal doses of an ultrashort barbiturate or isoflurane. Supplemental systemic or epidural analgesics can be administered if necessary. Urine output should be monitored in the perioperative period. If oliguria exists, fluids and perhaps a diuretic such as furosemide, mannitol, or dopamine should be administered. PMID- 1585608 TI - Anesthesia for gastric dilatation/volvulus. PMID- 1585609 TI - Anesthesia for feline urethral obstruction. PMID- 1585610 TI - Anesthesia for severe liver dysfunction. AB - By using these guidelines, we have safely anesthetized high-risk liver patients with minimal complications. By understanding the consequences of the underlying disease, prudent selection of agents that use alternate methods of excretion, careful perioperative support and management, and close observation during the postoperative period, the liver disease patient may be safely anesthetized with minimal complications. PMID- 1585611 TI - Anesthesia for cesarean section in the dog. AB - At the time of cesarean section, the mother may suffer respiratory depression, hypotension, increased gastric acidity, and increased predisposition to regurgitation, and the newborn may suffer anesthetic-induced respiratory depression. Preanesthetic metaclopramide, cimetidine, and anticholinergic agent are recommended. Sedatives can be administered if necessary. Neuroleptanalgesic and low-dose general anesthetic, with local anesthetic line-blocks, are preferred techniques. Supportive care of the newborn is mandatory. PMID- 1585612 TI - Anesthesia for cesarean section in the cat. PMID- 1585613 TI - Anesthesia for patients with head trauma. AB - Patients undergoing anesthesia soon after head trauma are at great risk for further neural damage during the anesthetic, especially if the head injury is severe or the anesthetic technique is suboptimal. Secondary complications of the anesthetic that are often lethal include hypoventilation, increases in ICP, airway obstruction, and brain-stem herniation. Anesthetic management of patients with head injury must include intravenous induction with barbiturates or narcotics, smooth endotracheal intubation, controlled ventilation with oxygen, and minimal amounts of inhalational agents. It is important to position the patient so that jugular veins are not occluded, in about 10 degrees head up position, and to avoid inducing patient coughing and straining. Recovery from anesthesia should be quiet and rapid, with the maintenance of a clear airway and the use of as little depressant medication post-operatively as possible. Oxygen should be provided. PMID- 1585614 TI - Anesthesia for patients with severe systemic debilitation. AB - Any patient presenting for anesthesia and surgery who has a severe debilitating problem is at great risk for a prolonged recovery, renal failure, or hypotension. A stable hemodynamic state should be maintained. Fluid homeostasis should be ensured. Anesthetic induction techniques using narcotics and benzodiazepines are my preferred approach, with maintenance of anesthesia incorporating isoflurane, narcotics, or both or the use of regional anesthesia. PMID- 1585615 TI - Anesthesia for patients with dehydration/hypovolemia. AB - Anesthetic drugs normally depress cardiovascular function and in a patient that is already dehydrated and hypovolemic can cause severe hypotension. Reestablishing intravascular volume with a balanced salt solution can return cardiovascular function to normal, and anesthesia must not be induced until the animal has been stabilized. PMID- 1585616 TI - Survey of the operation of dairy herd health schemes by veterinary practices in the United Kingdom. AB - A postal survey of 566 veterinary practices with dairy farms among their clients showed that the majority of the practices were very positive about the benefits of running a herd health scheme. Nevertheless, only a third of them were running a scheme, and most had attracted only a small number of clients. The size of the practice (in terms of the number of veterinarians and the number of dairy farming clients) was the most significant factor determining whether a practice was likely to run a herd health scheme, and the age of the veterinarians did not appear to have any affect. PMID- 1585617 TI - Effects of diet on plasma concentrations of oral anthelmintics for cattle and sheep. AB - Groups of parasite-free lambs and calves which were either housed and fed hay and concentrates or were grazing on pasture were dosed separately with the oral anthelmintics fenbendazole and ivermectin (lambs only). The plasma concentrations of the drugs and their major metabolites were monitored during the period of their metabolism and excretion. The peak plasma concentrations and the availability of the drugs, as estimated by the areas under the plasma concentration-time curves, were significantly less in the grazing animals. When similar groups of lambs were dosed orally with the inert marker chromium EDTA, which has a particle size similar to the anthelmintics, it was observed that a higher percentage of chromium was excreted by the grazing lambs during the first 40 hours after dosing, suggesting that the extent of absorption in the grazing animals was less than in the housed animals. PMID- 1585618 TI - Effects of atipamezole on xylazine sedation in ponies. AB - Atipamezole antagonism of xylazine sedation was evaluated in six ponies. Atipamezole (0.15 mg/kg) or saline was injected intravenously 15 minutes after the ponies had been sedated with xylazine (1.0 mg/kg). Arterial blood pressure and gases, pulse and respiratory rates, the electrocardiogram, nose-to-ground distance and a subjective sedation score were recorded. The pretreatment nose-to ground distance and PaO2 returned to normal sooner after atipamezole than after saline and the ponies' appetite and normal locomotion also recovered sooner. No significant differences were observed between the effects of saline and atipamezole on the other measurements. PMID- 1585619 TI - First report of a XX/XXY fertile goat buck. PMID- 1585620 TI - Embryo transfer legislation. PMID- 1585621 TI - Availability of medicines. PMID- 1585622 TI - Availability of medicines. PMID- 1585623 TI - Bovine protozoal abortion. PMID- 1585624 TI - Infection of a marmoset with the BSE agent. PMID- 1585625 TI - Studies on the pathogenesis of bovine ephemeral fever in experimental cattle. III. Virological and biochemical data. AB - In an attempt to define the nature of the response of cattle to ephemeral fever infection, a number of indicators of inflammation were monitored during clinical disease. The total Ca, Zn, Fe, Cu, glucose and phosphate in plasma, together with blood ammonia, were assayed relative to changes in the rectal temperature. CaT levels fluctuated markedly and hypocalcaemia occurred in 4 of 8 cattle. Plasma Zn and Fe values fell while plasma Cu levels rose markedly in all cattle. Mean levels of serum NH3 of 20-30 mumol l-1 rose to a peak value of 56 mumoll-1. Plasma glucose levels rose to a peak of 4.6 +/- 0.5 mMl-1 and the plasma phosphate levels fell from 2.4 +/- 0.1 mMl-1 to 1.17 +/- 0.2 mMl-1 during fever. Values of pCO2 fell from a mean of 46.9 +/- 3.6 mmHg to 36.4 +/- 3.1 mmHg and coincided with a rise in pH. Virus was isolated 73 h (+/- 23) after inoculation and persisted until 130 h (+/- 21). The common role of these parameters in generalised inflammation and ephemeral fever is discussed. PMID- 1585626 TI - Serological reactivity to Mycobacterium bovis protein antigens in cattle. AB - The serological response to 12 purified Mycobacterium bovis antigens were examined in an ELISA assay. These antigens included the majority of M. bovis protein antigens described to date and in most cases they were very similar to the M. tuberculosis antigens of the same molecular mass. The purified antigens were tested against sera from M. bovis infected cattle, M. bovis culture-negative cattle from infected herds and animals infected with related microorganisms, mainly other mycobacterial species. All the antigens gave strong reactions with at least some sera from the M. bovis infected group and showed cross-reactivity with some of the sera from the other two groups. The antigen with the highest specificity reacted strongly with only 60% of the M. bovis infected sera. Antigens that reacted with most or all of the M. bovis infected sera also gave the highest cross-reactivity with sera from the other two groups. These results indicate that a serological test based on any one or a combination of these antigens, without removal of the cross-reacting epitopes, would be unsatisfactory. PMID- 1585627 TI - A comparison of virulent and avirulent strains of Salmonella choleraesuis and their ability to invade Vero cell monolayers. AB - The mechanisms of invasion used by virulent and avirulent Salmonella choleraesuis were compared using a Vero cell invasion assay. Mouse virulent S. choleraesuis strain 38 and avirulent strain 9 were examined for their ability to invade and survive in Vero cells. The assay was performed by S. choleraesuis infection of the Vero cell monolayer alone and in the presence of various treatments applied to the Vero cell monolayers. Intracellular S. choleraesuis colony forming units were then counted to characterize the mechanism of bacterial uptake. Invasion was not affected by colchicine, but was significantly inhibited in the presence of cytochalasins B and D, chloroquine, and dansylcadaverine. Inhibition by the above substances suggested the importance of microfilaments and of receptor recycling in receptor mediated endocytosis. Both bacterial strains had decreased invasion in the presence of mannose and after enzymic treatment with trypsin. Mannose exposure caused a significant 48% decrease in the uptake of virulent S. choleraesuis 38 and a 28% decrease in avirulent S. choleraesuis 9. Inhibition of endosome acidification did not affect the virulent strain 38 as much as it affected avirulent strain 9. Results from these experiments suggested that Vero cell invasion by S. choleraesuis was due to host uptake by receptor mediated endocytosis, and was mediated in part by mannose-sensitive adhesins. Outer membrane proteins were extracted from the virulent and avirulent strain and compared using SDS-PAGE following surface protein labeling with 125I. Virulent S. choleraesuis 38 had a unique 35 kD protein. The outer membrane proteins of both strains were then examined by radio-immunoprecipitation and western blot using guinea pig polyclonal antisera and the 35 kD protein was again found to be unique to the virulent strain 38. Antisera against the 35 kD protein significantly inhibited invasion of Vero cells by S. choleraesuis strain 38. PMID- 1585628 TI - Extrachromosomal human immunodeficiency virus type 1 sequences are methylated in latently infected U937 cells. AB - Long-term human immunodeficiency virus type 1 (HIV-1) infection of the human monocytic cell line U937 resulted in a progressive loss of infectivity that was correlated with the accumulation of stable, extrachromosomal forms of viral DNA. Viral latency was also characterized by reduced levels of HIV-1 transcription. The structure and activity of extrachromosomal viral DNA (E-DNA) in a fully latent U937 cell line was investigated by molecular cloning and DNA transfection. The resulting 18-kb E-DNA clone was composed of an intact HIV-1 sequence flanked by 7 kb of host sequence to one side and 1 kb of host DNA to the other side. This configuration is the result of retroviral integration into a highly repetitive element of the Alu family. Transfection of the E-DNA clone resulted in the production of infectious virus, indicating that viral latency was not the result of mutations in the HIV-1 genome. Analysis of CCGG sites revealed extensive de novo methylation of viral sequences present within E-DNA. These results suggest that modification of extrachromosomal viral DNA sequences is a mechanism for HIV 1 latency in long-term infected U937 cells. PMID- 1585629 TI - Identification of amino acid residues critical for endonuclease and integration activities of HIV-1 IN protein in vitro. AB - HIV-IN protein, tagged with a hexahistidine tail was expressed in Escherichia coli and purified by a one-step nickel chelate affinity chromatography procedure. The purified IN protein was characterized in terms of its endonuclease and integrase properties in vitro. Specific cleavage and integration of HIV U5 LTR ends were observed in the presence of 2-5 mM Mg2+ or Ca2+. In the presence of 2 mM Mn2+, cleavage and integration occurred at additional sites indicating a decreased specificity. The properties of mutant IN proteins were examined in vitro. Deletion of 39 amino acids from the N-terminus and a minimum of 25 residues from the C-terminus impaired IN-mediated cleavage and integration activities. The results of site-directed mutagenesis experiments showed that residues critical for IN function are highly conserved. Mutations of conserved residues Asp64, Pro109, Asp116, and Glu152 adversely affected IN function in vitro. Mutations of nonconserved residues Gly189 and Thr112 had no effect. Mutation of a conserved Thr115 to Ala caused a near complete loss of Mg(2+) dependent integration activity, but only partially effected endonucleolytic cleavage activity of IN. These results suggest that not all conserved residues are involved in both endonucleolytic cleavage and integration activities of HIV IN. PMID- 1585630 TI - Baculovirus-expressed glycoprotein E (gE) of herpes simplex virus type-1 (HSV-1) protects mice against lethal intraperitoneal and lethal ocular HSV-1 challenge. AB - We have constructed a recombinant baculovirus expressing high levels of the herpes simplex virus type 1 (HSV-1) glycoprotein E (gE) in Sf9 cells. The expressed gE migrated on gels as a double band with apparent molecular weights of 68 and 70 kDa. The recombinant gE was glycosylated based on its susceptibility to tunicamycin treatment and was transported to the membrane of Sf9 cells based on indirect immunofluorescence. Mice vaccinated with gE developed high serum titers of HSV-1-neutralizing antibodies based on plaque reduction assays. gE vaccination also induced a strong delayed type hypersensitivity (DTH) response to HSV-1. In addition, mice vaccinated with the recombinant gE were protected from both intraperitoneal and ocular lethal HSV-1 challenge. To our knowledge, this is the first report in which vaccination with gE was shown to induce high neutralizing antibody titers, a DTH response, or protection against lethal HSV-1 challenge. PMID- 1585631 TI - Studies on compartmentation and turnover of murine retrovirus envelope proteins. AB - Several aspects of turnover and degradation of cell membrane proteins were studied in an NIH 3T3 cell clone expressing the env gene of Moloney murine leukemia virus ts1. Both internalization and shedding of the extracellular domain of the envelope protein gp70 occurred at the cell surface, albeit, in the case of shedding, only a very small fraction of gp70 was shed. The turnover rate of gp70 at the cell surface was similar to that of the same protein in the postendoplasmic reticulum intracellular compartment. In the presence of L methionine methyl ester, the transmembrane domain of the envelope protein Prp15E was degraded faster than gp70. PMID- 1585632 TI - A 12,500 MW protein is coded by region E3 of adenovirus. AB - There is an open reading frame between ATG291 and TGA612 in the early region E3 transcription unit of adenovirus 2 (Ad2) that could encode a protein of 12,500 MW (12.5K). To address whether this protein is synthesized, we generated an antiserum against a TrpE-12.5K fusion protein which was expressed in Escherichia coli. This antiserum immunoprecipitated a doublet of about 12.5K apparent MW from [35S]Cys-labeled cells infected with Ad2, Ad5, and various mutants in other E3 genes. Mutants in the 12.5K gene did not produce this protein, and an in-frame deletion mutant showed a protein with a corresponding decrease in size. Cell-free translation of hybridization-purified RNA indicated that 12.5K is coded by E3 mRNA i. mRNA i is relatively scarce, and 12.5K is synthesized in correspondingly small amounts. The 12.5K protein was synthesized at early and late stages of infection in comparable amounts. Pulse-chase experiments indicated that 12.5K has a half-life of about 10 hr. The function of 12.5K is unknown, and the 12.5K gene can be deleted without affecting virus growth in cell culture. However, 12.5K is likely to be important in vivo because the gene is highly conserved in both Ad2 and Ad5 (group C adenoviruses), and also in Ad3 (group B). PMID- 1585633 TI - Cloning, sequencing, and overexpression of gene 16 of Salmonella bacteriophage P22. AB - It has been suggested that gene product 16 of bacteriophage P22 forms a pore for DNA transfer and/or that it functions as a pilot protein guiding the DNA across the membrane. We have cloned gene 16 and determined the nucleotide sequence. Within the sequenced region there is an open reading frame that could encode a protein of 609 amino acids having a molecular weight of 64,366. The hydropathic plot of this protein does not reveal putative membrane-spanning regions as expected for a protein forming a membrane pore. Overproduction of gene product 16 in Escherichia coli was successful only in a mutant in which the La protease was inactivated. Gene 16 mutants of phage P22 were not able to infect recBCD mutants of Salmonella typhimurium nor was protein 16, synthesized in E. coli from a plasmid, able to substitute for the pilot protein of phage T4. It seems that gene product 16 is not a pilot protein in the meaning of binding to the ends of linear DNA, thus protecting it from degradation by nucleases. PMID- 1585634 TI - Synthesis and processing of the influenza virus neuraminidase, a type II transmembrane glycoprotein. AB - The influenza virus neuraminidase (NA), a type II transmembrane glycoprotein, is expressed at the surface of infected cells and is a major structural component of the virion. The kinetics of biosynthesis of NA, including modification of N linked sugar chains, association with GRP78-BiP, oligomerization, and transport to the cell surface, were examined in A/WSN/33 influenza-infected BHK cells. Prior to gaining endoglycosidase H (endo H) resistance, NA was found to transiently associate with GRP78-BiP (t1/2 approximately 5 min). The protein was synthesized as a monomer and within 10 min a significant fraction of it was chased into dimers and tetramers with a t1/2 approximately 15 to 20 min before endo H resistance was acquired suggesting that oligomerization took place in the endoplasmic reticulum. WSN NA remained completely endo H sensitive up to 15 min after synthesis, acquired partial resistance to endo H between 15 and 30 min (t1/2 approximately 25 min) after synthesis and exhibited heterogeneity in endo H resistant forms. NA was first detected at the cell surface 30 min after synthesis, increased to a maximum at 1 hr, after which it decreased, presumably due to incorporation into virions. The results on the biosynthesis of NA, a type II protein for which the three-dimensional structure is known, will be useful in structure/function and virion assembly studies. PMID- 1585635 TI - RNA packaging signal of human immunodeficiency virus type 1. AB - Cells infected with a recombinant vaccinia virus carrying the gag and pol regions of the human immunodeficiency virus type 1 genome (Vac-gag/pol) released human immunodeficiency virus (HIV)-like particles containing HIV-specific RNA. However, cells infected with another recombinant vaccinia, Vac-gag/pol-dP, derived through the deletion of an 85-base region (nucleotide positions 679-763) of the HIV genome between the primer binding site and the gag initiation codon of Vac gag/pol, produced HIV-like particles devoid of the HIV-specific RNA. This 85-base deletion was suggested to cause the collapse of a stable stem-loop structure of 46 bases (751-796) around the gag initiation codon. To examine the role of the stem-loop structure in the packaging of RNAs, we constructed a vaccinia vector plasmid that carried this 46-base sequence followed by the Sendai virus nucleocapsid (NP) gene. When both Vac-gag/pol-dP and this plasmid were introduced into cells, HIV-like particles released from the cells contained the NP gene RNA. However, another vaccinia vector plasmid, which carried the 46-base sequence in the midst of the NP gene, could not supply RNA for incorporation into HIV-like particles. Computer analysis of this plasmid sequence suggested that the 46-base sequence cannot form the stem-loop structure. These findings suggest that the stem-loop structure formed by the 46-base sequence is crucial as a packaging signal. PMID- 1585636 TI - Generation of reassortants between African arenaviruses. AB - Lassa (LAS) and Mopeia (MOP) viruses are African arenaviruses which are carried by wild rodents and occasionally transferred to humans. In humans and nonhuman primates, Lassa causes mortality in 60% of untreated cases, whereas Mopeia does not cause mortality and has been known to protect monkeys from lethal challenge with Lassa. These two African arenaviruses also differ in their lethality for suckling outbred mice and in their plaque sizes under agar overlay. MOP virus induces small plaques and lethal infection after intracerebral (ic) inoculation. In contrast, LAS inoculation does not kill mice and the virus induces large plaques. After coinfection of Vero cells with LAS and MOP viruses some phenotypic reassortants which produced small plaques and were not lethal for outbred mice were isolated and plaque-purified. Dot-blot hybridization using LAS and MOP cDNA probes specific for L and S RNA segments revealed a genotype consisting of the L RNA of MOP and the S RNA of LAS (MOP/LAS reassortant). Adoptive transfer experiments demonstrated an ability of immune splenocytes from CBA mice intraperitoneally infected with the MOP/LAS reassortants to protect recipient mice against lethal disease after ic inoculation with LAS virus. PMID- 1585637 TI - Reexamination of the coding potential of the HTLV-1 pX region. AB - The human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of adult T cell leukemia (ATL) and tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). In addition to tax and rex genes eight additional open reading frames are present in the pX region of HTLV-1. The possibility that these open reading frames can encode a protein in human cell lines persistently infected by HTLV-1 or in COS-1 cells transfected with a pX expressor plasmid was investigated. The results presented here indicate that tax and rex are the only proteins detected. Moreover, antibodies against proteins in vitro translated by five of the additional open reading frames of the pX region were not found in sera of ATL and TSP/HAM patients, further indicating that those proteins are not usually made in infected cells. PMID- 1585638 TI - Role of the host cell nucleus in the replication of African swine fever virus DNA. AB - An examination by autoradiography of African swine fever virus-infected alveolar macrophages pulse labeled with [3H]thymidine showed that, at early times of viral DNA replication, the grains were localized exclusively in the nucleus in 20% of the cells, while in 45% the label was found in the cytoplasm. In the remaining 35%, newly synthesized DNA was detected in both the nucleus and the cytoplasm. At later times, the percentage of cells with grains in the nucleus decreased considerably. Pulse-chase experiments indicated that the DNA synthesized in the nucleus is then transported to the cytoplasm. The presence of virus-specific DNA sequences in the nucleus was confirmed by in situ hybridization of infected macrophages. Similar hybridization experiments with African swine fever virus infected VERO cells followed by confocal microscopy also indicated the existence of a nuclear stage in the localization of the viral DNA. These results suggest a mechanism for African swine fever virus DNA replication with an initial stage in the nucleus followed by a cytoplasmic phase. Specific nuclear forms associated with the hybridization signal have been observed in African swine fever virus infected macrophages and VERO cells. The nuclear forms seen in macrophages are consistent with a mechanism for the egress of the viral DNA from the nucleus that involves initial budding at the nuclear membrane. PMID- 1585639 TI - Abrogation of IL-2 dependence by recombinant murine retrovirus containing v-myb. AB - Biological consequences of expression of v-myb gene in murine long-term T cell lines (CTLL-2 and HT-2) were studied using murine retroviral vectors. Expression of high levels of v-myb altered responses to interleukin (IL)-2, expression of surface markers, and growth characteristics of these cells. Interestingly, v-myb oncogene brings about growth-factor independence in IL-2-dependent T cell lines with concomitant induction of IL-2 mRNA and downregulation of IL-2 receptor synthesis. These results suggest a role for myb gene products in IL-2 gene expression. PMID- 1585640 TI - The Helminthosporium victoriae 190S mycovirus has two forms distinguishable by capsid protein composition and phosphorylation state. AB - Purified preparations of the Helminthosporium victoriae 190S (Hv190S) virus contain two sedimenting components that differ in capsid structure. The slower sedimenting component (190S-1) contained p88 and p83 as the major capsid proteins; the faster component (190S-2) contained p88 and p78. Previous peptide mapping studies have shown the three capsid proteins to be closely related. Analysis by SDS-PAGE of in vivo-radiolabeled Hv190S virions indicated that 32P was predominantly incorporated in p88. Significantly less was detected in p83 and none in p78. Similar results were obtained in in vitro phosphorylation studies using [gamma-32P]ATP and purified 190S-1 and 190S-2. The in vitro results suggest that the Hv190S virions copurify with a protein kinase activity that catalyzes the transfer of gamma-phosphate from ATP to a target protein, presumably p78 in the 190S-2 virions and p83 in the 190S-1 component. Selective chemical cleavage at tryptophan residues of in vitro 32P-labeled capsid proteins revealed four labeled peptides among the cleavage products of both p83 and p88. Radioiodination studies with intact Hv190S virions indicated that p88 and p83, but not the nonphosphorylated p78, were accessible to iodination, suggesting that capsid protein phosphorylation entailed conformational changes. PMID- 1585641 TI - Proteolytic processing of the plum pox potyvirus polyprotein by the NIa protease at a novel cleavage site. AB - The expression of potyvirus genomic RNA takes place through translation of its unique long and functional open reading frame into a large polyprotein that undergoes extensive proteolytic processing. Most of the cleavages are performed by the virus-encoded NIa protease, which cuts the polyprotein at defined sites that are characterized by conserved heptapeptide sequences. We have demonstrated in vitro cleavage activity by the plum pox potyvirus (PPV) NIa protease at a novel site, previously identified by sequence analysis, thus allowing a further refinement of the potyviral genetic map. This novel site is located 52 amino acids upstream from the site corresponding to the N-terminus of the CI protein (the NIa cleavage site previously considered the closest to the beginning of the polyprotein). The specificity of the processing was demonstrated by its abolishment when the Gln at position -1 of the cleavage site was changed to His. This novel NIa cleavage site was only partially processed, a characteristic that was not altered when its heptapeptide sequence was modified to become that of the efficiently cleaved NIb-CP junction. On the contrary, substitutions at the nonconserved position +3 had notable effects, positive or negative, on the efficiency of processing. These results show the relevance of sequence and/or conformational context outside the conserved heptapeptide for modulating the cleavage reaction catalyzed by the NIa protease. PMID- 1585642 TI - Mice immunized with a subviral particle containing the Japanese encephalitis virus prM/M and E proteins are protected from lethal JEV infection. AB - Extracellular subviral particles produced by HeLa cells infected with a recombinant vaccinia virus encoding the prM and E genes of Japanese encephalitis virus (JEV) were purified and characterized. These particles contained the JEV prM/M and E proteins embedded in a lipid bilayer, and RNA was not detected in particles using the polymerase chain reaction and primers recognizing a part of the JEV E gene. The particles were uniformly spherical with a 20-nm diameter and had 5-nm projections on their surface. Mice that received a single inoculation of the purified extracellular particles emulsified with Freund's complete adjuvant were fully protected against 4.9 x 10(5) LD50 of JEV. Comparison of the neutralizing and hemagglutination-inhibiting antibody titers and radioimmunoprecipitation data showed that immunization with the particles induced an immune response similar to that following inoculation with the recombinant vaccinia virus. PMID- 1585643 TI - The DNA polymerase gene from chlorella viruses PBCV-1 and NY-2A contains an intron with nuclear splicing sequences. AB - The deduced amino acid sequences of two eukaryotic chlorella virus (PBCV-1 and NY 2A) DNA polymerases are 90% identical and contain amino acid motifs typical of alpha-like (Family B) DNA polymerases. The open reading frames of both PBCV-1 and NY-2A DNA polymerases are interrupted by an identically located, small (101 or 86 nucleotides, respectively) intron that resembles eukaryotic nuclear-spliced messenger RNA introns. This discovery suggests that chlorella virus replication has a nuclear phase. PMID- 1585644 TI - The M RNA of impatiens necrotic spot Tospovirus (Bunyaviridae) has an ambisense genomic organization. AB - The nucleotide sequence of Impatiens necrotic spot virus (INSV) M RNA was determined from cDNA clones. The INSV M RNA was 4972 nucleotides in length with two open reading frames (ORFs) in an ambisense genomic organization. The larger ORF near the 3' end of the viral RNA, coding for a protein with a predicted molecular weight of 124.9 kDa, was in the viral complementary sense and produced the G2 and G1 proteins. A smaller ORF in the viral sense was capable of coding for a 34.1-kDa polypeptide, designated the NSm protein. Two subgenomic RNA species were detected in INSV-infected tissue that corresponded to the predicted sizes (3.3 and 1.0 kb) of the G2-G1 and NSm mRNAs. The ORFs were separated by a 478 nucleotide A-U-rich intergenic region similar to the regions found in other viral RNAs with ambisense ORFs. The intergenic region was predicted to form a stable stem-loop structure (-81.2 kcal/mole). The ambisense genomic organization is characteristic of the S RNA for members of the Phlebovirus, Uukuvirus, and Tospovirus genera in the Bunyaviridae family. This is the first report of an ambisense Bunyaviridae M RNA. PMID- 1585645 TI - Requirement for ICR-like sequences in the replication of brome mosaic virus genomic RNA. AB - Previous studies using a brome mosaic virus (BMV) RNA-2 deletion mutant (pRNA-2 M/S) and additional derivatives as reporters established that viral sequences resembling internal control regions (ICRs) 1 and 2 of tRNA gene promoters are vital to (+)-strand replication in protoplasts. Transfer of these mutations to genomic RNA-2 and functional analysis in protoplast, local lesion, and systemic infections revealed a sequence-specific requirement for bases within the ICR2 like motif. Despite the low (generally less than 20% of wild-type) and sometimes undetectable levels of replication of these RNA-2 mutants, sufficient p2a protein was produced to support at least modest levels of RNA-1, -3 and -4 replication in protoplasts. However, only those RNA-2 ICR2 mutants supporting substantial replication of the viral genome in protoplasts were capable of establishing local lesions in Chenopodium hybridum and systemic infections in barley, further establishing the essential role of the ICR-like sequences in viral infectivity. Upon passage through a second set of barley plants, accumulation patterns for progeny from inocula containing certain RNA-2 mutants paralleled those from wild type inocula, indicating repair of the introduced mutations. RNA stability and translatability were shown to be unaffected by the introduced mutations. BMV RNA 3 contains several ICR-like sequences, each of which was individually deleted. Whereas deletion of the 5'-terminal ICR2-like motif had little effect on RNA-3 accumulation in protoplasts or local lesion formation, it debilitated systemic spread in barley. Deletion of an internal ICR2-like motif at position 1100 decreased (+):(-) strand asymmetry from greater than 100:1 to 14:1, reduced RNA-3 replication in protoplasts to less than 15% of wild-type, and abolished local lesion and systemic infectivity. PMID- 1585646 TI - HTLV-I Tax is a zinc-binding protein: role of zinc in Tax structure and function. AB - We have examined the functional significance of the cysteine- and histidine-rich region (amino acids 22-53) of HTLV-I Tax. A modeling of this region suggests two possible overlapping zinc-finger-like motifs. Using a zinc blotting technique, we show that Tax binds zinc. An N-terminal deletion in Tax that removed this zinc finger region abolished the ability to bind zinc. Site-directed mutagenesis was used to generate 10 separate mutations so as to discriminate between the two alternative zinc-binding structures. Each Tax mutant was studied for its ability to trans-activate the HTLV-I LTR. Five of the ten mutations inactivated trans activation. Our results support that one of the two putative zinc fingers is an integral element of Tax structure. PMID- 1585647 TI - Isolation of the avian transforming retrovirus, AS42, carrying the v-maf oncogene and initial characterization of its gene product. AB - A novel avian transforming retrovirus was isolated from a chicken musculoaponeurotic fibrosarcoma. This virus (called AS42) induces tumors histopathologically indistinguishable from the original sarcoma after a long latent period when inoculated into newborn chickens. AS42 also exhibits a weak transforming activity when infected into chicken embryo fibroblasts (CEF). This virus is replication-defective and associated with a helper virus of subgroup A (called ASAV). An AS42-specific protein of about 100 kDa was immunoprecipitated from lysates of AS42-transformed CEF with antiserum directed against avian retrovirus virion proteins. Molecular analysis of the genomic structure of the AS42 virus has revealed that this 100-kDa protein represents a novel oncogene, v maf of cellular origin, which is fused with a part of the viral gag gene (Nishizawa et al., Proc. Natl. Acad. Sci. USA 86, 7711-7715, 1989). Interestingly, some size variation was observed among the gag-maf fusion proteins found in individual clones of transformed CEF. Consistent with this observation, Southern blot analyses and nucleotide sequence determination of several independent isolates of proviral DNA indicated that this virus segregates multiple forms of deletion mutants, probably through homologous recombinations among the repetitive sequences present within the v-maf coding region. PMID- 1585648 TI - Persistent infection of human adenovirus type 5 in human monocyte cell lines. AB - Adenovirus infection of human monocyte hybridoma cell lines and the fusion partner U937 was investigated. Adenovirus adsorbed poorly to these cells as well as primary human alveolar macrophages. The virus-binding experiments showed a 100 fold reduction in apparent viral binding to these cells compared to the permissive HeLa cells. Adsorption of adenovirus to these cells could be enhanced by preincubation of adenovirus with its antiserum. Following entry into the cells amplification of adenovirus DNA was detected starting at 2 days postinfection but few mature virus particles were produced. The infected cultures survived the infection and continued to grow for more than a year. In these chronically infected cultures, linear adenovirus DNA persisted up to 200 copies per cell and a small amount of mature virus was produced. Infectious center assay and cell cloning experiments showed that the majority of the cells in the chronically infected cultures harbor adenovirus genome. These results indicate that restriction of replication of human adenovirus type 5 at the late phase results in persistent infection of U937 and the human monocyte hybridoma cell lines. PMID- 1585649 TI - A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope. AB - Nucleotide sequence analysis of a 42-kb region of the vaccinia virus (strain Western Reserve) genome identified a gene with the potential to encode a 35.1-kDa polypeptide with properties of a membrane glycoprotein (Smith et al., J. Gen. Virol. 72, 1349-1376, 1991). The 317 amino acid open reading frame (ORF) has similarity with complement control proteins and a secretory vaccinia virus protein (C28K) which interferes with complement function. The predicted B5R gene product differs from the latter protein in that it contains a C-terminal hydrophobic sequence and may be membrane-associated rather than secretory. Transcriptional mapping by Northern blotting and S1 nuclease protection showed that the gene is transcribed both early and late during infection, with the early RNA start site located 60 bp upstream of the late start site that is present at 9 to -5 bp relative to the ORF. Nevertheless, translation of early and late mRNAs are predicted to produce the same polypeptide. A rabbit antiserum was raised to the predicted external hydrophilic domain of B5R expressed in Escherichia coli and used to immunoprecipitate a M(r) 42 K protein from vaccinia-infected cells. This protein was synthesized throughout infection, with a peak from 6 to 7 hr, and its production was inhibited by tunicamycin but not monensin. Western blotting of proteins from purified extracellular enveloped virus (EEV) or intracellular naked virus with anti-B5R serum showed that this M(r) 42 K protein and two higher molecular weight forms (Mr82 and 87 K) were present only in EEV. Anti-B5R serum inhibited comet formation by the IHD-J strain of virus on RK13 cells. B5R is the third vaccinia gene shown to encode an EEV glycoprotein, the others being the virus hemagglutinin gene, and gene SalL4R which encodes a group of lectin-like glycoproteins of M(r) 22-24 K. PMID- 1585650 TI - The polarity suppression factor of bacteriophage P4 is also a decoration protein of the P4 capsid. AB - We show that the product of the polarity suppression (psu) gene from bacteriophage P4 associates with P4 capsids. This association can occur when Psu is (i) provided in vivo from the P4 genome or from a plasmid or (ii) provided in vitro by mixing viable phage particles with Psu protein. Psu is unable to associate with the larger capsid of P4's helper phage P2. Discrimination of the P4 and P2 capsids by Psu appears to be independent of the presence of the P4 genome in the capsid, since P2 size capsids filled with P4 DNA cannot accommodate Psu association. P4 psu particles devoid of Psu are less stable than P4 particles carrying Psu. These results indicate that, in addition to its antitermination activity at Rho-dependent terminators, Psu is also a decoration protein that stabilizes the P4 capsids. PMID- 1585651 TI - Replication of HIV-1 and HIV-2 in human bone marrow cultures. AB - The bone marrow is a target organ for the human immunodeficiency virus (HIV), but the mechanisms by which suppression of hematopoiesis occurs during the course of HIV infection are not well understood. To study this issue, the effect of several different HIV-1 isolates (monotrophic and lymphotrophic) and one HIV-2 isolate on in vitro colony formation by BFU-E and CFU-GM from normal human marrow were examined. The monotrophic strain AD-87 (M) failed to replicate in marrow cultures as documented by RT, and colony formation by BFU-E and CFU-GM was unaffected by this virus. A derivative of this isolate AD-87 (M-P), which was replicated in peripheral blood lymphocytes (PBL), however, replicated well and markedly inhibited colony formation by BFU-E and CFU-GM. Two additional PBL isolates replicated less efficiently; neither inhibited CFU-GM but one consistently inhibited BFU-E colony formation. Inhibition of colony formation by the HIV-1 isolates was a late event, presumably a secondary lysis of cells, since up to 7 days after inoculation colony numbers were normal but diminished markedly by 10 days, and since only up to 10% of the cells of the monocyte lineage contained detectable virus by in situ, EM, and IFA studies. In contrast, the HIV-2 isolate was so lytic that by 4 days after inoculation the majority of the marrow cells were destroyed. PMID- 1585652 TI - Isolation and characterization of a highly divergent HIV-2[GH-2]: generation of an infectious molecular clone and functional analysis of its rev-responsive element in response to primate retrovirus transactivators (Rev and Rex). AB - A highly divergent HIV-2 designated as HIV-2[GH-2] was obtained from an AIDS related complex (ARC) patient in Ghana. A full-length molecular clone of this isolate was obtained and a biologically active clone was constructed. Its restriction pattern differed from that of prototype HIV-2[GH-1] in 25 of 35 restriction sites, but was strikingly similar to a previously characterized HIV-2 isolate from a Ghanaian (HIV-2ALT). The conserved integrase region (288-bp fragment) previously displayed 95% identity with that of ALT but 17-20% divergence from the HIV-2 prototype member, and a new distinct subgroup (HIV-2b) of HIV-2 consisting of GH-2 and ALT was postulated (Miura et al. 1991.) These isolates, however, were biologically distinguishable from each other by its replication capacity in a monocyte line, U937, in which GH-2 could not grow but ALT grew well. In addition, the nucleotide sequence of the LTR of this new isolate displays 21% divergence from that of prototype HIV-2[GH-1], but the core enhancer, Sp1 binding sites and TATA box were conserved. Although the 3' half of the env gene sequence which is deleted in HIV-2ALT clone showed 27% diversity from the prototype, functional differences in the rev-responsive element were not observed. PMID- 1585653 TI - Virus-cell membrane fusion does not predict efficient infection of alveolar macrophages by human immunodeficiency virus type 1 (HIV-1). AB - Alveolar macrophages (AM) are the principal target cells for HIV-1 in lung tissue. To investigate the mechanisms of HIV-1 infection and efficient replication in these cells we isolated AM from 14 HIV-1 negative donors and exposed them to two virus isolates, either N1T, which replicates well in T lymphocytic and monocytic cell lines, or ADA, a monocytotropic virus. Membrane fluorescence dequenching assays demonstrated that HIV-1/N1T fuses efficiently with AM plasma membranes at neutral pH and that this interaction requires cellular CD4. Despite efficient fusion, AM from eight of 14 donors were not susceptible to productive infection with N1T. In contrast, ADA replicated in all AM populations tested. Soluble CD4 blocked infection of AM by either N1T or ADA, indicating that, like membrane fusion, entry of infectious virus requires an interaction with cellular CD4. Analysis of HIV-1 DNA accumulation in infected cells by enzymatic amplification revealed that productive infection by ADA correlated with a high HIV-1 DNA copy number and abortive infection by N1T was characterized by little or no stable cDNA. These studies suggest that the differences between the two HIV-1 strains studied in their ability to replicate in AM reside in phases of the virus life cycle that follow virus-cell fusion. PMID- 1585654 TI - Retroviral envelope protein fusions to secreted and membrane markers. AB - We have analyzed a series of Moloney murine leukemia (M-MuLV) envelope (env) protein fusions to the marker proteins invertase and placental alkaline phosphatase (PLAP), expressed in Psi2 retrovirus packaging cells. The yeast invertase protein, fused at its third amino acid residue to the amino-terminal signal sequence and 17 residues of the mature M-MuLV env protein, retained its enzymatic activity and was secreted from mammalian cells. However, env protein fusions to the C-terminal portion of invertase were inactive. In contrast, some, but not all, env protein fusions at the C-terminal region of PLAP were enzymatically active: PLAP fusions containing long C-terminal portions of env localized to the rough endoplasmic reticulum (RER) and possessed low enzyme activity levels, while fusion constructs containing relatively short portions of the M-MuLV env gene localized to the Golgi and had higher activity levels. Those proteins that localized to the Golgi also were processed, in part, to forms of 67 to 68 kDa, the size of the mature PLAP protein. Since PLAP ordinarily is transferred to a phosphatidyl-inositol glycan tail (PIG-tail) in the Golgi and then transported to the plasma membrane, it appears that Golgi-localized PLAP-env fusions are processed imperfectly. PLAP itself, when expressed in Psi2 cells, accumulated at the plasma membrane and, unlike the PIG-tailed Thy-1 protein, was not incorporated into virus particles. Thus, the reported incorporation of the Thy-1 protein into M-MuLV virions does not appear to be a consequence of its glycoprotein tail. PMID- 1585655 TI - Cloning, sequence, and overexpression of bacteriophage T4 gene 51. AB - The nucleotide sequence of the 907-bp XbaI-EcoRV T4 DNA fragment containing gene 51 is presented. The sequence of gene 51 predicts a 249 amino acid peptide with an M(r) of 29387 and a pl of 6.34. We have cloned and overexpressed this gene in the T7 RNA polymerase system. The observed molecular mass of gp51 is in agreement with the sequence data. We also show that the low level of gene 51 expression usually seen is caused by an RNA stem-loop structure in the region between genes 26 and 51. In addition, discrepancies with the sequence published by other authors are indicated. PMID- 1585656 TI - Nucleic acid-binding properties of the alfalfa mosaic virus movement protein produced in yeast. AB - The movement protein of alfalfa mosaic virus (P3) was purified from yeasts transformed with an expression vector containing the P3 gene. Its nucleic acid binding properties were tested by electrophoretic retardation, nitrocellulose retention, and RNA-protein cross-linking. The recombinant protein had a higher affinity for single-stranded RNA and DNA than for double-stranded nucleic acids. Each nucleic acid molecule bound several protein molecules without sequence specificity. The binding was 80% inhibited by 0.2 M NaCl. These properties are qualitatively similar, but not strictly identical, to those of two other viral movement proteins, the 30-kDa protein of tobacco mosaic virus and the gene I product of cauliflower mosaic virus. PMID- 1585657 TI - Regulation of the activities of African cassava mosaic virus promoters by the AC1, AC2, and AC3 gene products. AB - DNA fragments comprising each of the promoter regions from the geminivirus African cassava mosaic virus (ACMV) were cloned into the pUC18-based vector, pG1, producing transcriptional fusions with the beta-glucuronidase gene (GUS) and nopaline synthase terminator sequence. The relative activity of each promoter construct was analyzed by a GUS expression assay of extracts from Nicotiana clevelandii protoplasts coelectroporated with the GUS reporter constructs and constructs in which individual ACMV open reading frames (ORFs) were placed under control of a cauliflower mosaic virus 35 S promoter. Results suggest repression of the AC1 gene by its gene product, which is required for ACMV DNA synthesis. The promoter activity observed for the single promoter for the DNA A genes encoding functions of spread and the regulation of replication (AC2 and AC3 ORFs) was unaffected by coelectroporation with any of the ACMV ORF constructs. Promoters for the AV1 (coat protein) gene and the two DNA B genes (BV1 and BC1) were activated by electroporation of the AC2 ORF construct. To a lesser extent promoters for the AV1 and BV1 genes were activated with the AC3 ORF construct. The same pattern of promoter repression and activation was observed when transgenic N. benthamiana plants expressing the GUS reporter constructions were inoculated with ACMV DNA A. PMID- 1585658 TI - Subacute sclerosing panencephalitis is typically characterized by alterations in the fusion protein cytoplasmic domain of the persisting measles virus. AB - Our recent extensive analysis of three cases of subacute sclerosing panencephalitis (SSPE) revealed intriguing genetic defects in the persisting measles virus (MV): the fusion (F) genes encoded truncated cytoplasmic F protein domains (Cattaneo et al., Virology 173, 415-425, 1989). Now this MV genomic region has been investigated in eight additional SSPE cases by PCR amplification, replacement cloning into a vector containing the F gene of a lytic MV, in vitro expression, and sequencing. In all cases at least part of the clones showed mutations leading to F protein truncations, elongation, or nonconservative amino acid replacements. It is proposed that alteration of the F protein cytoplasmic domain may play a critical role in the development of SSPE. PMID- 1585659 TI - Molecular cloning and sequence analysis of the mumps virus gene encoding the L protein and the trailer sequence. AB - We have cloned and determined the nucleotide sequences of the seventh gene of the Miyahara strain of mumps virus (MuV) encoding the L protein. The L gene is 6925 nucleotides in length and contains a single long open reading frame which is capable of coding for a protein of 2261 amino acids with a calculated molecular weight of 256,571 Da. The deduced amino acid sequence of the L protein of MuV showed significant homology with those of six other paramyxoviruses, human parainfluenza type 2 virus, Newcastle disease virus, Sendai virus, measles virus, human parainfluenza type 3 virus, and human respiratory syncytial virus. The predicted MuV L protein contained distinct elements thought to be essential for RNA polymerase activity. A noncoding sequence of 24 nucleotides downstream of the presumed polyadenylation site of the L gene showed significant complementarity with the leader sequence composed of 55 nucleotide at the 3' end of the genomic RNA. PMID- 1585660 TI - Vaccinia virus-mediated inhibition of host protein synthesis involves neither degradation nor underphosphorylation of components of the cap-binding eukaryotic translation initiation factor complex eIF-4F. AB - Recent reports indicated that vaccinia virus late mRNAs contain a unique 5' poly(A) leader sequence and that the in vitro translation of these mRNAs may be relatively cap-independent. These observations led us to examine the possibility that the mechanism of inhibition of host protein synthesis by vaccinia virus, like that of certain other viruses, involves specific modifications of the cap binding translation initiation factor complex eIF-4F. The eIF-4F complex was affinity-purified from human cells infected with vaccinia virus and analyzed by one- and two-dimensional electrophoresis and immunoblotting. No evidence of vaccinia virus-induced degradation of p220, as occurs during poliovirus infection, or alteration of phosphorylation of eIF-4E (p24), as occurs during adenovirus infection, was detected at the time of severe inhibition of host protein synthesis. PMID- 1585661 TI - The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication. AB - The ability of vaccinia virus to inhibit processes of cap-dependent translational initiation by inactivating the eukaryotic translation initiation factor 4E (eIF 4E) has been examined. Analyses of the quantities of eIF-4E present in either uninfected mouse L929 cells or vaccinia virus-infected cells showed that during the first 12 hr of virus replication, when there is a marked decrease in host gene expression in infected cells, there is no change in the total amount of eIF 4E present. Analyses of eIF-4E that was metabolically labeled with [32P] and then purified by affinity chromatography using m7GTP-Sepharose 4B, indicated that neither the incorporation of radiolabel into eIF-4E nor the amounts of eIF-4E capable of binding to cap structures changed significantly during virus replication. Immunodetection of phosphorylated and unphosphorylated eIF-4E in cell lysates fractionated by two-dimensional gel electrophoresis showed that the steady-state levels of phosphorylated and unphosphorylated forms of eIF-4E were similar in uninfected and virus-infected cells. These results suggest that vaccinia virus does not gain preferential translation of viral mRNAs over other mRNAs in the cell by reducing either eIF-4E phosphorylation or its ability to bind to the cap structure. PMID- 1585662 TI - Hepatitis B virus genomes that cannot synthesize pre-S2 proteins occur frequently and as dominant virus populations in chronic carriers in Italy. AB - The heterogeneity of hepatitis B virus (HBV) pre-S sequences coding for envelope proteins was tested by DNA amplification and direct sequencing of viral genomes from sera of 22 unselected chronic carriers resident in Southern Italy. The sequences of the dominant viral genome populations from 15 carriers were very similar to known published "wildtype" HBV genomes and showed no deletions. In contrast, in the HBV populations of six patients, deletions in the pre-S region, mainly clustered at the amino terminal end of the pre-S2 region, were found. Four of these mutant genome populations and those from another patient cannot express pre-S2 proteins due to deletions or a mutation of the translation initiation codon. Emergence of the pre-S mutant viruses either during the natural course of infection or after interferon treatment was found in follow-up sera of one and two patients, respectively. These data indicate a high prevalence of pre-S mutant viruses which cannot express pre-S2 and normal-size pre-S1 proteins. This has important implications for the usefulness of diagnostic pre-S protein assays and possibly for interferon treatment and the efficacy of new vaccines containing pre S proteins. PMID- 1585664 TI - The hospital in rural and urban districts. Report of a WHO Study Group on the Functions of Hospitals at the First Referral Level. PMID- 1585663 TI - Full-length cDNA sequence of dengue type 1 virus (Singapore strain S275/90). AB - The complete nucleotide sequence and the deduced amino acid sequence of the genome of dengue virus type 1 (Singapore strain S275/90) were determined from cDNA clones. The single-stranded, positive-sense RNA is 10,718 nucleotides in length and contains a single long open reading frame of 10,188 nucleotides encoding a polyprotein of 3396 amino acids. The genomic size and organization were found to be similar to that of other dengue virus serotypes. Both the nucleotide and deduced amino acid sequences were compared with the partial sequence of DEN1 (Nauru Island) and complete sequences of DNE2 (Jamaica), DEN3 (H87), and DEN4 (Dominica) virus genomes. PMID- 1585665 TI - [Nosocomial infections and infection medicine]. PMID- 1585666 TI - [Autochthonous parasitic zoonoses--a current problem. Part 3: Arthropod-induced zoonoses]. PMID- 1585667 TI - [Hemispheric specialization in man]. PMID- 1585668 TI - [Exercise-induced bronchial asthma in childhood]. PMID- 1585669 TI - [New results of oxygen multistep therapy research]. PMID- 1585670 TI - [Condensed evaluation of ambulatory illness classification]. PMID- 1585671 TI - [Robert Koch and Poland. A contribution to the origin of Robert Koch's scientific studies]. PMID- 1585672 TI - [Diagnostic importance of anti-Ro autoantibodies]. PMID- 1585673 TI - [Clinical significance of anti-Ro antibodies in autoimmune diseases]. PMID- 1585674 TI - [Differentiation of autoantibodies to extractable nuclear antigens using immunoblotting in various collagen diseases]. PMID- 1585675 TI - [A new enzyme immunoassay for quantitative determination of antinuclear antibodies]. PMID- 1585676 TI - [Therapeutic possibilities in systemic scleroderma]. PMID- 1585677 TI - [Differential diagnosis of systemic immunologic diseases with kidney involvement]. PMID- 1585678 TI - [Pleuro-pulmonary manifestations of systemic lupus erythematosus with special reference to bronchoalveolar lavage]. PMID- 1585679 TI - [Dental aspects of complex treatment of rheumatic patients with Sjogren symptoms]. PMID- 1585680 TI - [Significance of parietal cell antibody determination]. PMID- 1585681 TI - [Selected results of attitudes regarding nutrition behavior in the former East Germany]. AB - In studying the causes of individual nutritional behaviour not only the economic, social, demographic, cultural and other determinants are of importance but also psychological processes of decision and evaluation. For recording the attitudes, value-orientations and action goals a questionnaire was developed (72 items, 13 social and nutrition-related features). It was completed by 867 subjects aged between 18 and 65 years. The statistical analysis shows that the action determining goals investigated can be classified in 5 empirically developed, factorially validated scales (expenditure, health, enjoyment, matter of minor importance, stimulus). Besides, significant relationships were revealed between the scales and the social characteristics as e.g. sex, age, education, occupation, household size, cooking, mass catering, and self-assessment of body weight. PMID- 1585682 TI - Comparative studies of gastrointestinal tolerance and acceptability of milk chocolate containing either sucrose, isomalt or sorbitol in healthy consumers and type II diabetics. AB - The objective was to compare reaction of adult consumers of confectionery to milk chocolate made with either isomalt, sucrose or sorbitol. Test chocolate was eaten by subjects at home during 7 days in amounts chosen by them up to a maximum of 100 g per day. In a double-blind crossover trial isomalt chocolate was associated in healthy consumers (n = 58) with increased motion frequency, wind and flatulence compared with sucrose chocolate. However, the intensity of these gastrointestinal effects was predominantly slight and insufficient to affect acceptability. In separate crossover trials, reactions of Type II diabetic consumers to eating isomalt chocolate (n = 53) or sorbitol chocolate (n = 51) were compared to reactions when eating no chocolate. Both isomalt and sorbitol chocolate were associated with higher incidence of wind and flatulence than for no chocolate, but only sorbitol chocolate increased motion frequency. Again intensity of gastrointestinal effects was slight. It is concluded that isomalt has potential use in both regular and diabetic chocolate. PMID- 1585683 TI - [Effect of carbohydrate intake during a long distance run on work capacity and metabolism]. AB - The present study addressed the effects of carbohydrate consumption during endurance exercise on performance, energy turnover, and metabolism. Well-trained endurance runners consumed a beverage with (cho[+]) or without (cho[-]) carbohydrates during a long-distance run (46.6 km). The respiratory quotient (RQ), plasma levels of carbohydrate and fat metabolites, and of hormones (insulin, glucagon) were measured before, several times during, and after the run. The mean running speed for the entire distance was 13.6 and 13.4 km/h with the cho[+] and cho[-] beverage, respectively. The decrease in speed that was observed towards the end of the run was somewhat more pronounced with consumption of the cho[-] beverage. The RQ decreased during the run almost linearly. This decrease was independent of the consumed beverage. The changes in plasma levels of lactate, free fatty acids (FFA), glycerol, D-3-hydroxybutyrate (DHB), glucagon and insulin that occurred during the run were not affected by intake of the cho[+] beverage. However, intake of the cho[+] beverage prevented the decrease in plasma glucose observed towards the end of the run under control conditions, and eliminated the steep postexercise increase in plasma DHB. The intake of the cho[+] beverage also caused a rapid decrease in plasma levels of FFA and glucagon after the run, and slightly increased plasma insulin. The results demonstrate that ingestion of a carbohydrate-containing beverage during a long-distance run affects metabolism only during the final phase of the run and during the subsequent recovery period. Moreover, carbohydrate consumption improves performance only during the final phase of a long-distance run. PMID- 1585684 TI - [Insulin-like growth factor I--a connecting link between nutrition and growth]. AB - The influence of an increasing protein supply in combination with soybean oil upon the IGF-I concentration in the serum in correlation with growth was measured on 8 x 10 male Wistar rats. With a casein content of 0% in the food, the IGF-I level was 0.13 +/- 0.02 rU/ml. An IGF-I plateau of 0.74 +/- 0.07 rU/ml was reached at some 15% casein. The additional application of 3% soybean oil increased the IGF-I concentration significantly (P less than 0.01) up to 0.95 +/- 0.16 rU/ml. The investigations show a specific increase of the IGF-I synthesis by the addition of oil, which is paralleled by a further stimulation of the growth of the rats. The nutrition-dependent IGF production in the peripheral tissues (mainly liver) represents the connection link between the growth hormone axis (genetically potential growth) and the growth realizable depending on the supply with nutrients. PMID- 1585686 TI - Boiled coffee does not increase serum cholesterol in gerbils and hamsters. AB - In contrast to drip filter coffee, boiled coffee increases the serum cholesterol level in man. To identify the substance(s) responsible for this effect, it is necessary to find an animal model sensitive to boiled coffee. In this study, three groups of 20 male gerbils and three groups of six male hamsters were fed a control diet or a control diet supplemented with either freeze-dried boiled coffee or freeze-dried filtered coffee. At the end of the 5-week feeding period serum cholesterol levels were not different in either species fed the different diets. These results suggest that these animal species are not sensitive to boiled coffee, or that the cholesterol-raising factor in boiled coffee is lost during the process of freeze-drying. PMID- 1585685 TI - [Hematological parameters, selenium concentration and glutathione peroxidase activities in serum and the liver of rats at different selenium and vitamin E levels]. AB - The aim of the both experiments was to determine whether selenium or selenium/vitamin E supply of rats significantly influences the most important hematological criteria. With experiment 1 the influence of Se deficiency should be determined at two different times of growing. So 36 weaned rats were divided into 2 groups of 18 animals each, the half of them being decapitated at day 22, the rest on day 45. In experiment 2 with the aim to investigate a combination of deficient, adequate and excessive Se and vitamin E supply 90 weaned rats in 9 groups were decapitated at day 44. The basic diet contained 0.04 mg Se and 8 mg vitamin E per kg dry matter and was supplemented in exp. 1 with 0 mg or 0.2 mg Se and 30 mg vitamin E and in exp. 2 with 0 mg, 0.2 mg or 1.0 mg Se and 0 mg, 30 mg or 200 mg vitamin E. With Se deficiency Se concentration and GSH-Px activity in serum and liver were significantly reduced. With excessive Se supply Se concentration in serum was higher; there was no effect on GSH-Px activity. Vitamin E supply had no influence neither on Se content nor on GSH-Px activity in serum or in liver. In exp. 1 Se deficiency caused no clear changes of the analysed hematological criteria although the increase of MCV (+3%) and hematocrit (+7%) on day 22 and the increase of leucocytes (+43%) and the decrease of MCH ( 3%) and MCHC (-6%) on day 45 were statistically significant. In exp. 2 these results could not be repeated. The vitamin E supply was without significant effects on the examined hematological parameters. PMID- 1585687 TI - [Hormones in animal production--a health risk for the consumer?]. AB - In 1988 the EEC has banned the use of anabolic substances like hormones such as testosterone, progesterone and estradiol-17 beta in animal production. The use of these hormones is found to be effective in reducing the quantity of feed without any significant changes in the liveweight of the animal. Officially the EEC asserted that the prohibition of the use of hormones in animal production would protect the consumer. The USA permit the use of specific anabolics in animal production. These are applied on certain parts of the animals such as ear which in any case are part of the offal. Application of hormones does not result in any significant alteration in the hormonal level "in vivo". The quantity of hormones which may be ingested through meat is comparatively very small to the levels synthesized in the body of human beings, even in children. Additionally, these substances when introduced orally have no significant physiological activity. The World Health Organization (WHO) has concluded in 1987 that use of hormones in animal production has no adverse effect on the health of the consumer. The prohibition of these hormones seems to be more for political and economical reasons than for their harmful side effects for the consumer. PMID- 1585688 TI - [Anesthesiologic problems in the elderly]. AB - Nowadays approximately 20% of all patients operated are older than 60 years of age. So it seems to be interesting to investigate the effect on the increase of systemic disease of these patients, to estimate a proper anaesthesiological management. Anaesthesiological problems occur pre- and postoperatively because of restrictions of the cardiovascular and respiratory system, compromised renal function and defeds of the CNS. Therefore preoperatively registration and therapy of these risks are necessary, however diagnostic evaluation cannot be standardized. There is no typical anaesthesia for the elderly. PMID- 1585689 TI - [Candida infection after aortic valve replacement--a case report with special reference to the literature]. AB - Candida-infections of the heart are rare and often combined with a difficult diagnostic and therapy as well as a high mortality rate. That's why we critically finished off diagnostic and therapeutic instructions are present valid by means of a case. To give a proof of a candida-infection is very difficult and demand to include all of clinical and paraclinical directions as well as the often echocardiographic control of implanted strange materials. In the present time the mostly used therapeutic regime is caused of the explantation of strange material already in the case of a suspicion of an infection with candida and the consequent and combined application of antimycotica with the favoured combination of amphotericin B and flucytosin. PMID- 1585690 TI - [Effects of various contraceptives on laboratory parameters in diagnosis of thyroid gland function with special reference to the free hormones FT4 and FT3]. AB - The effect of different oral contraceptives with an estrogen content of 30-50 micrograms ethinyloestradiol on thyroid hormones and the binding protein TBG was investigated and quantified for 200 women. The sera of 220 normal persons were analysed to get normal values for T3, T4, FT4, Ft3, TBG and TSH. Under the influence of antiovulatory hormone treatment the thyroxin binding globulin increased to values above 32 mg/l in 65% of all euthyroid women. The median for T4 changed from 97 to 120 nmol/l, respectively from 2.3 to 2.8 nmol/l for T3. We think the combination of TSH, FT4 and T3 to be the best analytical tool for differential diagnosis of hyperthyreose. The FT4 level was nearly independent of variations in TBG concentration, so we can accept the normal range from 10-28 pmol/l for patients with contraceptives as well. In 16% of these euthyroid women the T3 level proved to be in the hyperthyroid range with values above 3.6 nmol/l. The FT3 determination is stronger influenced by protein changes caused by oestrogens than FT4 and should not be accepted as a favourite parameter for patients with oral contraceptives. PMID- 1585691 TI - [The incidence of silent myocardial ischemia]. AB - Retrospectively evaluated was the patient population of the years 1982 to 1988 which underwent ergometric investigations concerning the appearance of silent myocardial ischaemias. In 256 reactions of exercise ischaemia of patients with definitive coronary disease in 47 cases angina pectoris appeared (18.4%). Reactions of ischaemia in a large area of the breast wall showed, compared with a small area of ischaemia, a significantly higher proportion of symptomatic episodes (34.3% vs 13.0%, P less than 0.05). Ergometric exercises lying below the norm of age were more frequently accompanied by symptomatic ischaemias than ischaemic reactions, which only appeared in a good area of performance (26.0% vs 11.4%, P less than 0.05). In addition to this more anginose complaints were found in patients, whose ischaemic reaction was accompanied by an insufficient frequency response (28.1% vs 9.8%, P less than 0.05). PMID- 1585692 TI - [Travel medicine]. AB - The medical advice for travellers into tropical and subtropical climatic zones is essentially a task of the physician. Thereby the medical advice and the prophylactic measures should restrict themselves not only to risks of infection, but they must--as far as possible--comprise all health risks. The travellers who bear with themselves a health risk deserve particular attention on the side of the physician. Precarious from the medical point of view are travels with infants and babies as well as travels of pregnant women. The personal, age- and sex specific health situation, the subjective behaviour as well as style of travelling and lifestyle play an essential role. The personal situation of the traveller is to be taken into consideration concerning the risk of the travel, so that the advice regarding the travel can in every case be only an individual medical action. According recommendations in the field of tropical medicine the performance of protective inoculations the prescription of a suitable chemoprophylactic drug against malaria as well as if the occasion arises of a medicine cabinet for travelling is necessary. The postexpositional after-care after the return, the so-called returners' examination should not be neglected. PMID- 1585693 TI - [Acquired antithrombin III deficiency]. AB - Acquired antithrombin III (AT III) deficiency is based on either decreased activity or synthesis, increased loss or increased consumption. The activity of AT III is decreased in metabolic acidosis, hyperlipoproteinemias and by lipid peroxides. Chronic liver diseases especially liver cirrhosis are associated with very low levels of AT III due to insufficient hepatic synthesis, reduced transcapillary flux ratios, diffuse intravascular coagulation and loss in the ascites. Gastrointestinal loss of AT III may occur in patients with active inflammatory bowel diseases. AT III deficiency is observed in nephrotic syndrome when urinary loss of protein exceeds 5 g/d. During hemodialysis we have not found low AT III levels. Disseminated intravascular coagulation is characterized by activation of the coagulation system and increased consumption of AT III. AT III complexes with activated coagulation factors are subsequently cleared by the reticuloendothelial system. PMID- 1585694 TI - [Critique of using the Staverman sigma reflection coefficient in the theory of microcirculation]. AB - The usage of the reflection coefficient sigma defined by Staverman within the theory of microcirculation in tissues requires free perfusion through semipermeable membranes, which does not exist in the reality of tissue blood supply. In accordance to the principle of continuation of the hydraulics the reflection of colloidosmotic particles at semipermeable membranes in tissues does not comply with the condition of steady state regimes. Considering this fact the relevance of sigma in theoretical and practical investigations is challenged. PMID- 1585695 TI - [Leipzig Medical Society (founded in 1829)]. AB - The Leipzig Medical Society was founded in 1829 by Justus Radius. More than 100 years this interdisciplinary association was a scientific and cultural centre which promoted scientific life and professional training of the municipal physicians and the university staff. Therefore the Leipzig Medical Society contributed to reputation of Leipzig as an cultural and scientific centre during the last years of the 19th and the beginning of the 20th century. PMID- 1585696 TI - [New aspects of mechanical cardiopulmonary resuscitation]. AB - New results in the area of mechanical cardiopulmonary resuscitation indicate that during external cardiac massage, the blood flow is achieved both by direct cardiac compression and a generalized increase in the intrathoracic pressure. While, in accordance with the classical theory, the heart is compressed between the sternum and the vertebral column, the thoracic pump mechanism requires a consideration of all blood-carrying structures within the thorax as elastic tubes or chambers that are capable of being compressed by externally administered pressure. Only such variations of the technique presently used may be of benefit which can be achieved with simple adjuncts and which have a positive effect on both mechanisms of blood flow. PMID- 1585697 TI - [Resuscitation in childhood]. AB - Children, especially newborns and infants up to 5 years of age, are no "small adults" even in emergency care medicine. Therefore, differences in function of the vital organs heart and lung related to growth must be taken into account when dealing with cardiopulmonary resuscitation (CPR) in infants. Resuscitation procedures have to be performed more rapidly, and knowledge in recognizing pediatric emergencies or in pediatric drug therapy are essential for successful life support management in these patients. Better instruction and training of emergency physicians, emergency medical services personnel, and laypersons may help improving the poor survival rates of resuscitated infants and children. PMID- 1585698 TI - [Cerebral resuscitation]. AB - The present paper illustrates the physiological basis of brain function as well as the pathophysiological and neurochemical cascades during cerebral ischemia and subsequent reperfusion. It is emphasized that brain resuscitation preferably focuses upon those cerebral functions or structures, respectively, which are not definitely damaged until the early period of recirculation. Finally, current experimental considerations and already clinically established concepts in treatment of ischemic brain injury are pointed out. Their principles of action and their therapeutical value in cerebral resuscitation following cardiocirculatory arrest are discussed. PMID- 1585699 TI - [The protocol book I. An important contribution to the history of the German Cancer Society (1900-1907)]. AB - On initiative of E. von Leyden the committee for cancer research, the origin of the present German Cancer Society was founded in Berlin in 1900. In 1991 in the Charite the original minute book of the committee of the years 1900 to 1907 was found. This historical document gives interesting insight into the beginnings of the German combat against cancer, themes treated, organisational questions and particulars of persons. PMID- 1585700 TI - [Recent progress in resuscitation]. PMID- 1585701 TI - [Current status of preclinical resuscitation. An overview based on recent literature and personal results]. AB - Cardiopulmonary resuscitation is one of the most important topics in modern emergency care medicine. Especially the management of the prehospital cardiac arrest is a region of interest. This article is an attempt to show the current situation of the out-of-hospital resuscitation in the german-speaking area. In an own analysis of 166 resuscitations by emergency physicians and by consideration of results from other groups we found an outcome between four and seventeen percent finally successful resuscitations. The main prognostically favourable factors seem to be the following: non-traumatic cause for the cardiac arrest, ventricular fibrillation as the primarily ECG-statement and begin with CPR within ten minutes. PMID- 1585702 TI - [Transcutaneous electric stimulation of the heart]. AB - Transcutaneous cardiac pacing had been introduced in the 1950s, but was given up because of severe side-effects. In the 1980s, this technique became again popular thanks to technical improvement. These are the indications: Adams-Stokes syncope, hemodynamically significant SA or AV blocks, significant bradycardias, overdrive stimulation in tachycardiac arrhythmias. In cardiocirculatory resuscitation, this method is not very successful (as are all other techniques of cardiac stimulation), if electromechanical dissociation has occurred. This shows, that this method has to be employed without delay, especially since there are new models, which can easily be used in the ambulance. One can only conclude, that all ambulances and helicopters staffed with physicians trained in emergency medicine should carry this equipment. The article reports on the technique, the handling and the literature on transcutaneous cardiac pacing. PMID- 1585703 TI - [Importance of developmental psychopathology for understanding psychiatric disorders and diseases in childhood and adolescence]. AB - Though the concept of developmental psychopathology is broadly discussed nowadays, a real integration of the different aspects of developmental psychology, developmental neurology and developmental physiology is not yet achieved. Elements that have to be considered to arrive at such an integrative view are pointed out. Sex differences and individual differences as well as the issue of continuity and change of behavior in the developmental process, the meaning of risk factors and protective factors and prediction research have to be considered. The importance of the developmental perspective with respect to the classification of psychopathological features is stressed and the problems that arise when trying to integrate this perspective into the existing classification schemes. Finally, it is shown how--by means of logistic models--the complex interaction between very heterogeneous factors, for example the connection between biological and psychosocial influences in the developmental process, can be described. PMID- 1585704 TI - [Dimensions of coping with chronic pain--a replication study]. AB - Clinical-psychological research on pain conceptualizes pain as a transactional process. There, important components are pain-experience, pain control (coping with pain) and subjectively felt pain-related stress. The intent of one preceding study (Geissner, 1991) was to describe, analyze, and validate behavioral and cognitive aspects of pain control and emotional and behavioral aspects of pain related subjective stress. The purpose of the present study is to replicate the factors of pain-processing, gained by exploratory data-analyses. 162 patients with headache, back pain and joint pain answered the revised version of the set of questionnaires used in the former study. Analyses are done by means of confirmatory factor analysis (LISREL 7 by Joreskog & Sorbom) and with admission of steps to optimize a solution found. 3 Dimensions of more behavioral aspects of pain control are identified: Mental distraction, relaxation and counteractivities. Also, 3 dimensions of cognitive aspects of pain control are found: Cognitive restructuring, planning skills to deal with the pain, and self assurance of ones own skills. The dimensions of subjectively felt pain-related stress are (1) helplessness/depression, (2) anxiety, and (3) anger. All dimensions prove to be factorially homogenous and structurally distinct. In regard to the solution found in the preceding study, differences are small. Therefore, it can be said, that the results gained formerly are replicable. Findings from correlational and regression-analytic studies further support the validity of the dimensions of pain-processing. PMID- 1585705 TI - [Sleep disorders: strategies for managing conflict by insomnia patients]. AB - The investigation compares 136 insomniacs with 102 healthy controls with respect to their coping strategies. Coping strategies are evaluated with the questionnaire FKBS. This questionnaire measures 5 different coping strategies: TAS--turning against subject; TAO--turning against object; REV--reversal; PRN- prinzipialisation; PRO projection. Insomniacs seem to react less aggressive than healthy controls. They also show less projections, i.e. they do not believe in a hostile intention of a situation or a counterpart. These differences could be shown on the level of behaviour as well as experience. With the personality traits of the FPI (Freiburger Personlichkeitsinventar FPI-R) there are some significant correlations. Finally there exists also a correlation between the strategy TAS and the incidence and intensity of depressive symptoms (i.e. state variabels). PMID- 1585706 TI - [Correlation of speech disorders and disorders of ego concept in schizophrenic patients]. AB - Texts of schizophrenic speakers show significantly more incoherence than those of patients with non-schizophrenic syndromes and normals. In our theory incoherence means a disorder in the implicitly dialogical structure of texts. It is based on deficits in the capacity of taking the role of the other person in social communication. These deficits can be conceived as a common structure of schizophrenic speech disorders and the symptoms of ego-dissociation typically found in schizophrenia. The author supposes, that the deficits in the process of role-taking in social context are caused by fundamental disturbances in self awareness and self-consciousness of schizophrenics. These disturbances are called Grundverhaltnisstorung. PMID- 1585707 TI - [Process outcome research exemplified by client-centered psychotherapy and short term psychodynamic psychotherapy]. PMID- 1585708 TI - [Training of aggressive children in residential treatment ages of five to seven years]. AB - The paper reports about strategies in behavior modification with aggressive children (sensu Petermann and Petermann, 1991) in special education ("Heimerziehung"). New results of treatment with nursery students are discussed. The modified conception (single and group sessions with child/children) are illustrated. Single-Case hypotheses were tested with the help of reversal designs (based on 105 observations). The differences of means between the phases of the observation (incl. the t-tests) are evaluated. The single-case analyses showed positive effects. Only the support by parents guarantees positive long-term effects. PMID- 1585709 TI - [Transluminal coronary extraction atherectomy. Method, acute results, angiographic and clinical follow-up]. AB - Transluminal coronary extraction-endarterectomy is an alternative interventional approach for treatment of coronary artery disease. The atherectomy system consists of a catheter assembly including a cutter and torque tube which is rotated at a relatively low rate of 750 rotations per minute, when introduced to the coronary artery over a guide-wire via a guiding catheter. Excised tissue is withdrawn from the coronary artery by suction applied through the catheter by means of an attached vacuum bottle. We report acute results in 18 patients and the clinical outcome of 14 patients who up to now underwent angiographic follow up catheterization after 6 months. Initial angiographic success (residual stenosis less than 50%) using TEC-atherectomy alone was obtained in 6/18 patients (33%), 11/18 patients (60%) required additional PTCA in order to achieve primary success (9/18) or to treat total occlusion (2/18) after TEC-atherectomy. Major complications consisted in 1-vessel perforation with non-Q-wave-infarction but no need of surgical intervention and 2 occlusions due to dissection (treated with PTCA). 14 patients underwent angiographic follow-up (6 months) and restenosis (greater than 50%) was confirmed in 7 patients (50%). Considering the low primary success rate of TEC-atherectomy alone and the tendency to high restenosis rate, we cannot recommend it as an alternative to conventional PTCA in general clinical practice. Further studies should be designed to directly compare TEC-atherectomy to PTCA in specific patient subgroups (e.g. bypass grafts, intraluminal thrombus, diffuse disease) in order to define the role of this interventional device. PMID- 1585710 TI - [High frequency current catheter coagulation using pulsed energy delivery. Results with isolated myocardial tissue]. AB - The feasibility and efficacy of pulsed radiofrequency (RF) current delivery was assessed and compared to results obtained by continuous energy delivery. Energy was delivered to ventricular preparations of isolated porcine hearts (HAT 100, 500 kHz, Osypka, FRG). In the pulsed mode, impulse duration and pause duration were varied between 50 and 500 ms. Total duration of coagulation was 30 s in all cases. The depth of induced lesions was significantly enhanced by a short impulse and pause duration (50-70 ms) compared to continuous RF energy delivery. At long pause durations (200-500 ms) and short impulse duration, depth and diameter of lesions significantly decreased. The incidence of sudden increases in impedance was markedly attenuated when energy was delivered discontinuously. Thus, pulsed RF energy delivery can be used to enhance the depth of RF lesions. The decreased incidence of sudden rises in impedance during pulsed energy delivery further enhances the feasibility of RF coagulation. An improvement in heat transfer to deeper tissue layers can be considered as the mechanism responsible for these effects. PMID- 1585711 TI - [Biophysical aspects of high frequency catheter ablation. Studies of the significance of sudden changes in impedance]. AB - To determine the effects and the underlying mechanisms of sudden rise of impedance during radiofrequency (RF) catheter ablation, 60 RF applications were delivered to isolated preparations of ventricular myocardium at three different power levels (mean: 3.7, 11.3, 19.3 watts). Pulse duration was 30 s, current voltage and catheter tip temperature were continuously monitored. Impedance rise occurred during 34 of 60 applications; the incidence of impedance rise increased at higher power levels. Impedance rise was significantly more often observed when the preparations were superfused with heparinized blood compared to saline solution (p less than 0.05). Catheter-tip temperature during radiofrequency application without impedance rise was significantly lower compared to applications with impedance rise (mean = 108 degrees C vs. 121 degrees C, p less than 0.01). The increase of catheter-tip temperature and maximal-tip temperature following impedance rise was significantly higher in blood when compared to saline solution (mean = +48 degrees C vs. +13 degrees C (p less than 0.001), Tmax: 121 degrees C vs. 245 degrees C). Following impedance rise, insulation defects of the electrode catheter and vaporized crater formation of the myocardium was often observed. CONCLUSIONS: During radiofrequency catheter ablation impedance rise occurs following overheating of the catheter electrode (greater than 110 degrees C). After impedance rise, catheter-tip temperature markedly increases. Insulation defects of the catheter and vaporized craters in the myocardium frequently occur after impedance rise. The results have important implications for the clinical use of RF-currents for catheter ablation; energy application should be immediately stopped after the occurrence of impedance rise. PMID- 1585712 TI - [Excimer laser coronary angioplasty after primary unsuccessful PTCA]. AB - Excimer laser coronary angioplasty is a new technique for ablation of coronary stenosis, however, the indications for its application are still controversial. We describe two male patients, 60 and 65 years old, who underwent unsuccessful balloon PTCA with a short, concentric and calcified coronary stenosis, although balloon inflation pressure was increased to a maximum in both cases. Excimer laser angioplasty following the failed procedures showed no evidence for tissue ablation angiographically, but a repeat attempt with balloon angioplasty was successful in both cases. Thus, laser angioplasty may be considered as an adjunct technique to balloon angioplasty after a failed PTCA in resistant, non-inflatable lesions. PMID- 1585713 TI - [Rate of success and restenosis of PTCA in patients over 75 years of age]. AB - In 82 patients (pts), ages 75-90 years (52 m, 30 f; mean age 77 +/- 3 years) with mainly unstable angina (59 pts) or acute myocardial infarction (7 pts) a PTCA or recanalization was attempted. Successful PTCA was achieved in 57 of 69 pts (83%); occlusions could be reopened in all six pts with myocardial infarction and totally occluded infarct related artery, and in three of seven pts with stable or unstable angina pectoris. The primary success rate of PTCA alone in pts with unstable angina was 81%, and improved to 92% in pts with stable angina. Sixteen procedures were multiple vessel and six were multiple lesion PTCA, so that the lesion-related success rate of PTCA was higher (87%). One patient died in connection with the procedure (procedure related-mortality 1.2%), two pts underwent myocardial infarction (2.4%), one patient emergency bypass grafting (1.2%). The in-hospital mortality was 4.9% and concerned exclusively patients with unstable angina and unsuccessful procedure. Local complications at the puncture site occurred in two patients. The angiographic restenosis rate of PTCA was 58% (44% in patients with stable and 63% in patients with unstable angina pectoris). Seventeen patients with 19 restenoses had successful repeat PTCA; reintervention failed in two patients. We conclude that PTCA can be performed in patients of old age with a resulting comparable primary success rate as in younger patients. Complications seem to be more frequent. The restenosis rate is higher, but with regard to stable and unstable angina, not significantly so. The prognosis in patients with unstable angina and unsuccessful procedure is apparently unfavorable. PMID- 1585714 TI - [Cardiovascular risk factors and restenosis after PTCA]. AB - We prospectively investigated the influence of the cardiovascular risk factors hypercholesterolemia, smoking, diabetes mellitus, and arterial hypertension on the occurrence and extent of restenosis after successful coronary dilatation (PTCA). Of the 103 patients included in the study, control coronary angiography was obtained in 75 (73%) after 173 +/- 117 days. The restenosis rate (82 stenoses), defined as greater than or equal to 50% loss of initial gain in percent diameter stenosis, was 37%. Older age, male gender, and a history of diabetes mellitus were associated with a significantly increased mean extent of restenosis (p less than 0.05). In patients with hypertension, the initial success of dilatation was less than in controls without hypertension (p less than 0.05), and restenosis tended to be enhanced (p = 0.06). The risk of restenosis was unaffected by smoking and the presence of hypercholesterolemia. In spite of the mostly insignificant influence of single cardiovascular risk factors, the extent of restenosis clearly increased with the number of risk factors. PMID- 1585715 TI - [Measuring blood flow velocity in the coronary sinus with Doppler catheters]. AB - Measurements of the coronary sinus blood flow velocity with Doppler catheters (Medtronic Floscan; Millar DC201) were performed to assess coronary flow reserve and significance of coronary artery stenosis. In seven patients with normal coronary angiogram coronary sinus blood flow velocity (Doppler catheters) and coronary sinus blood flow volume (thermodilution) were simultaneously recorded. Coronary flow reserve was calculated as the quotient of the peak flow velocity (peak flow volume) and resting flow velocity (resting flow volume) after infusion of 0.5 mg/kg dipyridamole intravenously. The correlation coefficient was r = 0.88. Coronary sinus blood flow velocity was measured in 31 patients at resting conditions and after injection of contrast media during coronary angiography. At resting conditions blood flow velocity was 3.6 +/- 1.5 cm/s (n = 31), 3.5 +/- 1.8 cm/s (n = 9; controls), and 3.6 +/- 1.1 cm/s (n = 9; significant stenosis of the left anterior descending; not significant). After injection of contrast media flow velocity amounted to 2.2-fold resting flow in controls and to 1.5-fold resting flow in patients with stenoses of the left anterior descending artery (p less than 0.01). Measurement of coronary sinus blood flow velocity with Doppler catheters is a valuable adjunct for determination of coronary flow reserve and for assessment of stenosis severity of the left anterior descending artery. Continuous on-line monitoring of phasic flow velocity provides important information of the myocardial perfusion, e.g., during angioplasty. PMID- 1585716 TI - [Reliable Quick value management by self determination]. AB - Because of the considerably increased risk of thrombembolic complications after implantation of mechanical heart valves, lifelong anticoagulation is required. In the face of frequently unsteady prothrombin-time (PT)-values, a stable anticoagulation is one of the most difficult tasks in attending patients with heart-valve-prosthesis. If PT is out of the therapeutic range, the risk of bleeding or of thrombembolism increases disproportionately. Two differently trained groups of phenprocoumon-treated patients monitored their PT themselves for 6 months by means of a coagulometer, and they also determined their weekly dose of phenprocoumon. PTs were therapeutic 80.5% resp. 93.8% of the time. Intensive training and care maximized safety of anticoagulation. PMID- 1585717 TI - [Unexpected complication of anticoagulation after implantation of a coronary stent]. AB - After stent implantation there is a high risk of acute stent thrombosis. Therefore, a very aggressive anticoagulation drug regimen is necessary. Two patients developed large hematomas of the upperarm that where presumably caused by automatic blood pressure measuring equipment or by a tourniquet used during blood collection. In one patient a complete paralysis of the ulnar and radial nerves resulted. PMID- 1585718 TI - [The functional interaction of androgens and thyroid hormones in regulating male sexual behavior]. PMID- 1585719 TI - [The phenomenon of the preliminary light interference-encoding representation of visual information in the optical space of the retina in the living eye]. PMID- 1585720 TI - [The quantitative analysis and topographic mapping of the EEG: the methods, problems and clinical use]. PMID- 1585721 TI - [The contribution of the neostriatum to the rhythmic organization of brain activity and the adaptive behavior of animals]. PMID- 1585722 TI - [The rationale for the criteria of allowable heat conditions of man working in a heated microclimate]. PMID- 1585723 TI - [The effect of a heat-producing industrial microclimate on the rate of biological aging of the body]. AB - While detecting the biological and cardiopulmonary age the authors have demonstrated that the long-term work under the conditions of the heating industrial microclimate promotes acceleration of biological body aging. In the intensification of the aging process, of great importance is the time at which one starts working under the heating microclimate conditions. Based on the data obtained the conclusion is drawn that employment of the persons over 40 years may be restricted in relation to so-called "hot" occupations. PMID- 1585724 TI - [Impulse acoustic and mechanical processes and their medico-biological evaluation]. AB - Impulse mechanical and acoustic processes whose action on the body of man may result in unfavourable consequences are ever widely practiced today in industry and in the environment. Impulse processes are characterized by certain physical peculiarities which determine the specificity of their biological effect. In turn, this gives rise to the problems of their hygienic estimation and standardization. At the same time out of the diversity of physical parameters which characterize impulse noise and vibration, one should choose, for hygienic estimation and standardization, only those of them that are responsible for the biological effect to the greatest degree. Different authors suggest different approaches to the hygienic standardization of those processes, which depends on what parameters are recognized by them as more adequate to their biological effect. PMID- 1585725 TI - [Acoustic vibrations and the present. The effect on the body and prevention]. PMID- 1585726 TI - [Current aspects of the etiology, pathogenesis, clinical picture and prevention of vibration disease from local vibration]. AB - Vibratory pathology goes on occupying the leading position in the pattern of occupational diseases. As to the industrial sources of local vibration, a hand power tool is most dangerous. The authors review differences in approaches to the estimation of vibratory disorders in the USSR and abroad, provide the main classifications of the vibratory syndrome and vibratory disease. Show that the pathogenesis of vibratory disease rests on a complex mechanism of neuroreflex and neurohumoral disorders leading to the development of congestive excitation followed by stable changes both in the receptor apparatus and different parts of the nervous system. The clinical symptomatology may include neurovascular disorders, lesions of the neuromuscular system, impairment of the bones and joints, alterations in metabolism, and so forth. In elaborating current measures aimed at vibratory disease prevention, use was made of the data of the prognosis of vibratory pathology risk. Measures for primary and secondary medical prophylaxis, new methods of early diagnosis, pathogenetic therapy with the use of stimulants of non-specific body resistance are described in detail. PMID- 1585727 TI - [The effect of altitude factors on the human body]. AB - Negative consequences of the impact of alpine factors on the body of man are described. Alpine acute lung edema is one of the dangerous diseases that may develop under alpine conditions. This may affect not only beginners but also aborigines of the mountains, who return to the places they come from after a temporary stay in lowlands. Acute brain edema is regarded as no less severe condition. It may occur in about 1.2% of the people who climb to a height of 4500 5000 m. Primary alpine pulmonary arterial hypertension and chronic alpine cor pulmonale are fairly prevalent under alpine conditions. PMID- 1585728 TI - [The biological effects and criteria for assessing the danger of laser radiation]. AB - Biological effects of laser radiation (LR) are determined by the absorption properties of the irradiated tissues and physiological characteristics of radiation. The high intensities of the effect are accompanied by melting, evaporation, substance ionization, formation of shock and acoustic waves. Under the action of the low-intensity LR there prevail photochemical, photobiological and thermal processes. The action of LR of one or another wave length is determined by the initial stages of its interaction with biological substrate. The biostimulating action of LR is widely used in clinical medicine. On the contrary, the effects that give rise to morphofunctional lesions of biological tissues determine the necessity of elaborating preventive measures ensuring protection of man from LR. It is generally accepted that thresholds of the damaging action on the retina and skin may be used as the main criterion for maximum allowable level (MAL) basing. In addition to the changes observable in the directly irradiated tissues, many authors point to a possibility of functional disturbances on the part of certain organs and systems of the body, followed by the formation of asthenic and vegetovascular syndromes. The experimental and clinical data confirm that the body may develop common nonspecific changes which, together with the local damaging effects, can be regarded as criteria for an adverse action of LR and, therefore, taken into account in MAL derivation. PMID- 1585729 TI - [Electromagnetic radiations from computer video terminals and their effect on health]. AB - The paper is concerned with a brief analysis of the reported data on hygienic, epidemiological and experimental estimation of the electromagnetic radiation (EMR) of a video-terminal (VDT). The results of the author's investigations are presented. Based on the data obtained it is concluded that low-intensity wide band EMR occurs in work places of VDT users. One should bear in mind that the biological action of EMR has not been studied so far. PMID- 1585730 TI - [Current problems of the effects of contact ultrasound in medicine and other branches of the national economy]. AB - The physiological and hygienic estimation of the working conditions of the new occupational groups of medical workers who service ultrasound (diagnostic, surgical, sterilization, and physiotherapeutic) equipment has demonstrated the intensity of contact ultrasound in the area of contact with hands to undergo changes within wide limits; exposure also changes, correspondingly by a factor of 10 or 10(2), amounting on the average to 1.2-1104 joules for different occupational groups. As a result of the long-term exposure to ultrasonic sources, the workers may develop neurovascular dose-dependent disorders in the form of angiodystonic syndrome of vegetative polyneuritis of the hands. The rate of the augmentation of constant shifts of the thresholds of vibration sensitivity may constitute 1.3 and 0.9 dB per year for those exposed to low and high-frequency sources, respectively. The principle of the frequency dependence of the effects of contact ultrasound is thus based; the maximum permissible level of factor is corrected with regard to the spectral parameters. The joint action of air and contact ultrasound has been examined and the additive effect has been revealed. This made it possible to establish a decreasing correction (5 dB) for the maximum permissible level of contact ultrasound characterized by a more remarkable biological action. The hygienic classification of contact ultrasound has been elaborated, the use of a complex of preventive measures has been based. PMID- 1585731 TI - [Maintaining the homeostasis of the human body in the extreme north]. AB - It has been shown that men living in the Extreme North experience the tension of thermoregulation and its effectors. The main systems that maintain thermal balance of the body are the cardiovascular system and external respiration taking an active part in the processes of physical and chemical thermoregulation. The double load of the key system leads to non-economic and rapid spending of the functional reserves and risk of early development of disadaptation phenomena. The authors worded a scientific concept of the systemic organization in the maintenance of temperature constancy of the internal medium of man in the Extreme North, which permits estimating the degree of the participation of the subordinated subsystems in thermoregulatory processes. PMID- 1585732 TI - [Speech production and speech comprehension of dysgrammatic speech of preschool children]. AB - The language comprehension and production abilities of 15 preschool children with developmental language disorders (LD) (4;11 yrs.-7;1 yrs.) and 15 control children (3;8 yrs.-4;7 yrs.) were investigated. For this purpose a test consisting of 135 picture cards was devised. On the production task (plural and comparative forms) the majority of the LD children performed significantly poorer than the control children. The results of the comprehension tests (plural and comparative forms and short sentences) showed marked deficits for the majority of the LD children (11 of 15), especially (but not only) in the identification of single forms. These combined expressive-receptive deficits should be considered in an etiological concept of developmental dysphasia. It is discussed whether these deficits are indicative of far-reaching disorders in the processing of language. PMID- 1585733 TI - [Behavioral disorders in infants and young children: a contribution to psychopathology of early childhood]. AB - In a study on the psychological development of children born at biological and psychosocial risk adverse temperamental characteristics and psychopathological symptoms of 362 children were determined at the ages of 3 and 24 months. Adverse temperamental characteristics were measured with the help of behavioral observations in standardized situations. Symptoms were assessed in a highly structured parent interview. The results showed a higher-than-average rate of disturbed children, which increased from 15.5% at the age of 3 months to 19.5% at two years. Hyperkinesis was the most prevalent disturbance. Whereas no sex effect was found among infants, the 2-year-old boys manifested more symptoms and had more adverse temperamental characteristics than the 2-year-old girl. Sex differences in symptom patterns were similar to those seen in later childhood. The course of early disturbances was characterized by low persistence and stability. Four fifths of all infant disturbances had remitted by the age of two years. A small number of early problems (i.e. eating disorders) turned out to be predictive of later disorders. PMID- 1585734 TI - [Psychotherapy continuing education in child and adolescent psychiatry]. PMID- 1585735 TI - [Subgroups of hyperkinetic disorders--explorative studies with reference to questionnaires and immunologic parameters]. AB - In this paper, the main questions examined are: 1. The relationship between clinically diagnosed hyperkinetic syndrome (HKS) and 3 questionnaires for parents (Child Behavior Checklist (CBCL) by Achenbach and Edelbrock, Enzephalopathie Fragebogen by Meyer-Probst and 10-Item scale by Conners). 2. The relationship between the clinical psychiatric diagnosis and the questionnaires and allergological parameters. In order to answer these questions, a sample of 122 psychiatric patients with "extraversive" behavior disturbances (HKS: N = 104, other "extraversive" disorders, mainly conduct disorders (EVD): N = 18) was examined prospectively and sequentially. The preliminary results are: a) The children with HKS, the children with EVD and the children with HKS and conduct disorder could be differentiated by several subscales (Especially by "introversive" symptoms) of the CBCL and the Fragebogen by Meyer-Probst. The Conners scale showed significant differences between the groups on only one item. b) The children with HKS, especially those without conduct disorder, had two to three times as many allergies as the children with HKS and conduct disorders or those with EVD. PMID- 1585736 TI - [Side effects of clozapine in therapy of psychotic disorders in adolescents. A retrospective clinical study]. AB - A retrospective study was conducted of 53 consecutive inpatients (through 1990) with psychotic disorders. The patients were between 13 and 18 years of age. In all cases this was the first time they had been treated with clozapine. The adverse effects seen under clozapine are discussed. During the use of clozapine assessments were made of liver enzymes, leukocytes, blood pressure and body temperature. There was an increase in liver enzyme values in 37.7% of the patients, leukopenia under 4000/mm3 in 15.1%, an increase in body temperature in 3.8% and bradycardia together with hypotensive dysregulation in 1.9%. PMID- 1585737 TI - [Anorectic reactions in low intelligence]. AB - Six female in-patients suffering from anorectic reaction are described. Difficulties in diagnosis and differences between these patients and anorectic patients of normal intelligence are discussed. The main finding is that in all six cases there was an extremely close and symbiotic mother-child relationship and a weak or absent father. Relevant life events in the nuclear family (new partner for the mother, illness in the father) then triggered the eating disorder. PMID- 1585738 TI - [Comment on the contribution by E. Forster: Psyche and person]. PMID- 1585739 TI - [Obstetric cw-Doppler--results of a study of normal values. Effect of different variables on results]. AB - Using a 4 MHz continuous wave Doppler device reference values for resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries as well as umbilical artery were established based on 510 patients with uneventful pregnancies and deliveries. Percentiles are more suitable localisation gauge than are standard deviations. Neither RI nor PI of maternal arteries proved to be dependent on gestational age in the observation period. If the heart rate are in physiological ranges no clinically relevant effect on the results were observed in either the maternal of the foetal copartment. By contrast umbilical artery shows a definite linear relation between the indices measured and gestational age. A significant effect of placental site on the measurement was found in both, uterine and arcurate arteries, but only the differences found in arcuates were of clinical value. An increase of diastolic notching was observed in both, uterine and arcuate arteries during pregnancy. Mostly only one vessel showed diastolic notching when observed in normal pregnancy. With a lateralized placenta the condition was more probable on the contralateral site. PMID- 1585740 TI - [Postpartum diabetes screening: value of fructosamine determination]. AB - After birth of an infant with a birthweight of 4000 g or more maternal glucose tolerance should be examined. We measured blood glucose values after a 100 g oral glucose challenge and compared them with serum fructosamine values of the same subjects. 40 women who had given birth to an infant with macrosomia (group I) were matched with 40 women who had delivered babies with normal birthweight (group II). Impaired glucose tolerance was found in 6 women (15%) of group I, and in one woman (2.5%) of group II. Fructosamine values were within the normal range in each of the seven women (1.74 + 0.2 mmol/l vs 1.73 + 0.2 mmol/l). Thus, fructosamine determination is not sensitive enough to detect impaired glucose tolerance in asymptomatic women post partum. It is not feasible to replace the oral glucose tolerance test in screening for gestational diabetes mellitus. PMID- 1585741 TI - [Psychosexual behavior as a risk factor for cervix cancer]. AB - Seventy-two patients with cervical cancer (n = 24), ovarian cancer (n = 24), or no disease (n = 24) were questioned about sexual activity and personal relationships. The interviews were conducted in a semistandardized fashion according to the Tubingen Sexual Therapy Scale. Patients with invasive cervical cancer did not have a larger number of sexual partners, an earlier age of first intercourse, greater sexual activity or less stable relationships than patients with ovarian cancer of healthy women. There was no statistical difference among the groups with regard to the relationships. However, patients with cervical cancer reported greater degrees of satisfaction with both sexuality and relationships. PMID- 1585742 TI - [Fetal toxoplasmosis--a dilemma?]. PMID- 1585743 TI - [A rare site of distant metastases of progressive cervix cancer]. AB - A report is given on 2 patients radiologically treated because of cervical carcinoma stage III respectively IIb. Both patients showed distant metastases in the breast, one of them 17 months, the other one 10 years after radiotherapy. PMID- 1585744 TI - [The gynecologic clinic of the Munster Westphalia Wilhelm University--beginnings, chronology and statistics]. PMID- 1585745 TI - [Predictive value of the tumor marker combination CA-125 and beta-2-microglobulin in ovarian cancer]. AB - Beta-2-Microglobulin (b2m) and or Ca-125 levels were measured in 367 serum samples of 66 ovarian cancer patients. CA-125 was found to be a suitable tool, even in single use, to monitorise the clinical course of the disease with acceptable sensitivity (o. 89) and specificity (o. 94). B2m showed a sensitivity of the same level (o. 87) the specificity of it however proved to be low (o. 48). In consequence of its low specificity the b2m as a single marker is not applicable in ovarian cancer. However, the addition of b2m to CA-125 resulted in higher specificity and sensitivity, as b2m probably has a different spectrum and yielded correct results at that points of the follow-up where CA-125 produced pseudo-positive or pseudo-negative results. The combination of b2m and CA-125 tumormarkers seems to be a suitable tool for follow-up ovarian cancer patients under and after treatment. PMID- 1585746 TI - [Malignant melanoma in gynecology]. AB - The malignant melanoma mostly is situated on the skin, the vulva being more often affected then expected in relation to its share in the total body surface. The peak of incidence lies in the fifth and sixth life decade. Five types of the tumor are known: lentigo maligna melanoma, superficial spreading melanoma, nodular melanoma, acrolentiginous melanoma and non-classifiable melanoma. For estimation of prognosis and choice of adequate mode of therapy histopathological examinations with regard to the level of invasion according to Clark and Chung, histomorphometric evaluation of the depth of invasion suggested by Breslow and the pronostic index of Schmoeckel and Braun-Falco are useful. The operative therapy of choice is the extensive tumor excision. In case of extended local invasion radical vulvectomy is indicated, in certain cases combined with inguinal, sometimes even pelvic lymphonodectomy. In inoperable cases radiotherapy may be tried, but success seems to be poor. Polychemotherapy may induce remissions, but hardly a prolongation of survival. New therapy trials are dealing with immunmodulation, mostly using different substances of biological response modifiers. The prognosis of malignant melanoma of the vulva must be considered to be poorer than that of melanomas in other sites of the body, local recurrence is frequent, the five year survival rate being 30-35%. Whether pregnancy does have an effect on melanoma growth is still unknown. Early stages of melanoma disease may be treated without interrupting pregnancy, whereas advanced stages require termination of pregnancy, followed by specific tumor therapy. PMID- 1585747 TI - [The function of fibrin in wound healing]. AB - Physiology of wound healing especially in its first phase is the basis for understanding application of fibrin sealant. The several components have been reported. PMID- 1585748 TI - [Closure of vesicovaginal fistulas from the urologic viewpoint with reference to endoscopic fibrin glue technique]. AB - Indications and results of conventional operative closure of iatrogenic vesicovaginal fistulas (24 patients) and exclusively endoscopic fibrin sealing (6 patients) have been reported. The primary closure rate of the first mentioned method is 88 per cent, but 66 per cent in cases of endoscopic fibrin sealing. The last method is reported in detail. PMID- 1585749 TI - [Fibrin glue in premature rupture of fetal membranes]. PMID- 1585750 TI - Cholesterol palmitate in amniotic fluid: confirmation of a simple, rapid, inexpensive, and reliable indicator of fetal pulmonary maturity. AB - The cholesterol test was previously described and preliminary experience suggested it might be a rapid, inexpensive, and reliable indicator of fetal lung maturity. In this expanded series of 1342 patients delivered of infants within 72 hours of amniotic fluid analysis, the predictive value for mature test was 98.6%. Predictive value for immature test was 55.4%. For the phospholipid profile the predictive value was 97.0% for a mature test result, 31.2% for an immature result. These observations, coupled with its methodologic simplicity, make the cholesterol palmitate test a good first step in a cascade scheme of tests for fetal lung maturity and a valuable test in a facility where the phospholipid profile is not available 24 hours a day. PMID- 1585751 TI - [Modification of cerebral hemodynamics by invasive routine diagnostic procedures]. AB - By means of cw-Doppler-ultrasonics pulsation curves of anterior cerebral arteries were recorded before, during and after a necessary capillary blood sampling in 12 premature newborns. Patients were stable and needed no oxygenation. Blood pressure and transcutaneous oxygen saturation have been recorded simultaneously. The most important hemorheological parameters were within normal range. Immediately following irritation pulsatility indices increased, partly diastolic reflux phenomena could be observed. Finishing irritation values went back to starting position very fast. It is supposed such strong changes of cerebral vascular resistance could be the reason of cerebrovascular damages in non sedated premature newborn babies. PMID- 1585752 TI - [A problematic case of dysfibrinogenemia in gynecology]. AB - Following an hymenal incision in a thirtheen years old patient a haemostaseological examination was done. A hyperfibrinolysis was supposed. In spite of a good clinical recovery values remained pathological, so we had to suspect a dysfibrinogenaemie. Only a rapid examination of all attainable family members was able to secure the diagnosis: Dysfibrinogenaemie. Dysfibrinogenaemia is not a to rare case, that such a diagnostic problem may arise in every department. PMID- 1585753 TI - [Comment on the contribution by D. Hofmann and G. Carle-Grewe: results of mostly vaginal delivery of breech presentation]. PMID- 1585754 TI - Phototherapy of atopic dermatitis with ultraviolet radiation. AB - Studies were conducted in order to evaluate the efficacy of different ultraviolet wavelength regions for the treatment of atopic dermatitis, the risks associated herewith and the in vivo effect of ultraviolet radiation (UVR) on the bacterial skin flora. In bilateral left-right comparisons, adult patients suffering from atopic dermatitis were subjected to treatment with lamps mainly emitting ultraviolet radiation A, UVA, (315-400 nm), UVB (280-315 nm) and combined UVA UVB, UVAB, respectively. UVAB proved to be most efficacious, with objective and subjective statistically significant superiority to the other types of UVR. UVB was found to be the least efficacious of the three, while the efficacy of UVA was found to lie in between UVAB and UVB. UVAB yielded clearing or considerable improvement in 90% of the patients, while UVA and UVB did so in about 70% of the subjects. Objective differences were less pronounced than subjective ones. The two most common side-effects, xerosis and first-degree burn, were tolerable and clearly correlated to the UVB content of the UVR sources. Uncommon side-effects included polymorphic light eruption (all three types of UVR) and folliculitis (UVB). A typical patient with atopic dermatitis undergoing phototherapy with UVB or UVAB was found to receive an erythemally effective dose of 1 J/cm2 per year, a figure considerably lower than that for UVB-treated psoriasis patients, who, according to previously reported data, receive an annual dose of 4J/cm2. Treatment for 15 years from the age of 25 years will result in an increase in the risk of non-melanoma skin cancer by the age of 60 of 1.15 compared with the risk in untreated individuals. The risks with phototherapy for atopic dermatitis were thus judged to be small. Phototherapy with UVB radiation was shown to possess in vivo antistaphylococcal properties, which were paralleled by clinical efficacy. It is concluded that phototherapy is an effective mode of therapy in patients with mild or moderate atopic dermatitis. PMID- 1585755 TI - Mode of action of dithranol, pharmacokinetics/dynamics. PMID- 1585756 TI - Clinical studies with a novel dithranol formulation (Micanol) in combination with UVB at day-care centres. AB - The clinical effect, side effects, cosmetic properties and the patients preference between Micanol and other dithranol formulations were investigated in three separate studies combining UV-B phototherapy and a short contact dithranol regimen. Good clinical results without difference between Micanol and other dithranol formulations were obtained. Side effects, cosmetic properties and preferences were mostly in favor of Micanol. Therefore, a high patient compliance can be obtained with the new dithranol formulation. PMID- 1585757 TI - Short-contact treatment at home with Micanol. AB - The efficacy of home treatment of psoriasis with a new dithranol formulation, Micanol, was investigated in three studies. They were carried out according to a randomized, within-patient comparison design. In a 4-week pilot study Micanol was compared with placebo (10 patients) and in two 6-week studies Micanol was compared with dithranol 1% in petrolatum (33 patients) and with dithranol 1% in Amitase stick (16 patients). Micanol was found to be effective and well suited for treatment at home in all studies. The vehicle itself did not improve the psoriasis plaques. The rate of clinical improvement was faster for dithranol in petrolatum and Amitase stick than for Micanol. The prevalence and severity of erythema, burning and staining of skin and clothing were far less for Micanol. Approximately half the number of patients preferred dithranol in petrolatum or Amitase stick and the other half preferred Micanol. PMID- 1585758 TI - An open, parallel groups, study of the importance of thoroughness of application in the treatment of psoriasis with a dithranol cream (Micanol). AB - Earlier studies have suggested that the rate of healing is somewhat slower for the new microencapsulated dithranol formulation, Micanol, than for petrolatum or paraffin based formulations. The less smeary Micanol formulation may need more vigorous application. A population of 29 patients with chronic, stable plaque type psoriasis was divided into two groups, both receiving short contact treatment. One group received standard patient information while the other received information stressing the importance of being thorough when rubbing the dithranol cream into the lesions. Regarding composite sign severity score, there was a significant difference (about 50%) in favour of the extra information group after 6 weeks. This result suggests that thoroughness of application is an important factor for the rate of healing in short contact treatment of psoriasis with Micanol. PMID- 1585759 TI - A novel dithranol formulation in the over night treatment of psoriasis at home. AB - The objective of this study was to compare the clinical efficacy and acceptability of two dithranol creams (Micanol and Amitase) in patients with plaque type psoriasis treating themselves daily at home. Thirty-five patients started with Amitase (0.1%) and 37 with Micanol (0.1%) applied at night in this 6 week single-blind parallel groups comparison study. Patients who responded more slowly than a theoretically estimated "standard" rate of improvement had their concentration increased to 0.25% at the visit after 2 or 4 weeks. By the end of the study slightly more than half of the number of patients remained on 0.1%. There was no difference between the treatment groups. In comparison with the level at start the composite sign severity score for patients in the Amitase group was reduced by 24% after 1 week, 36% after 2 weeks, 49% after 4 weeks and 62% after 6 weeks. The reduction in the Micanol group was similar. Patients in the Micanol group showed after 1 week of treatment more irritative reactions than patients in the Amitase group. At all follow-up visits, staining of perilesional skin was more prevalent in the Micanol group. Staining of clothing was, however, far more prevalent and severe for patients given the Amitase cream. It may be concluded that Micanol is an important alternative for home treatment of psoriasis. PMID- 1585760 TI - Short- and long-contact therapy using a new dithranol formulation in individually adjusted dosages in the management of psoriasis. AB - This study compares two treatment regimens, short- and long-contact dithranol in individually adjusted dosages, using a new formulation (Micanol) in the management of psoriasis. It was designed as a six week, randomized, open, parallel groups study. Twenty-two in-patients and 27 out-patients were included with either plaque type or small patch type of psoriasis. Patients in the short contact group started using daily applications of 1% Micanol for an average of 13 minutes. The concentration and the application time were then gradually increased and after six weeks of treatment the corresponding averages were 2.5% and 185 minutes. Patients in the long-contact group started with daily applications of 0.1% Micanol for an average of eight hours. After six weeks the corresponding averages were 0.33% and 14 hours. The composite sign severity score (CSSS) was defined as the sum of scores for lesional erythema, desquamation and induration divided by three. The CSSS constituted the primary efficacy variable and was reduced by 73% after six weeks in the short-contact group and by 78% in the long contact group. Side-effects were of low severity. There were no differences between neither treatment groups nor types of psoriasis apart from more staining of clothing in the short-contact group. This study suggests that Micanol is well suited for both short- and long-contact regimens in individually adjusted dosages and may be used for in- as well as out-patients. PMID- 1585761 TI - The history of dithranol and related hydroxyanthrones, their efficacy, side effects, and different regimens employed in the treatment of psoriasis. A review. PMID- 1585762 TI - Erythrocyte volume and haemoglobin concentration in haemoglobin H disease: discrimination between the two genotypes. AB - Erythrocyte volume and haemoglobin concentration in individual red cells from 62 patients with Hb H disease: 37 with H genotype (alpha-thalassaemia 1/alpha thalassaemia 2) and 25 H/CS genotype (alpha-thalassaemia 1/Hb Constant Spring) were measured using the H*1 haematology analyser. All 25 cases with H/CS genotype, the more severe genotype, had microcytes (red cells with a volume smaller than 60 fl) less than 35% and hypochromic red cells (red cells with haemoglobin concentration less than 28 g/dl) more than 35%. A discriminant function, the ratio between the percentage of hypochromic red cells and the percentage of microcytes (Hypo/Micro), was proposed. Most of the H/CS patients (76%) had Hypo/Micro greater than 2.5 whereas those of H patients (82%) were below 2.5. Red cell volume histograms were also characteristically different between the two genotypes: the H/CS had a peak between 60 and 90 fl while the H genotype showed a peak at or very close to 60 fl, indicating a greater degree of microcytosis. Increased hypochromia with a slight decrease in cell size of H/CS red cells suggests that the poor degree of haemoglobinization has no linkage or very little role in disturbing the synthesis of membrane proteins and their assembly to the plasma membrane. PMID- 1585763 TI - Selenium, glutathione peroxidase and oxidative hemolysis in sickle cell disease. PMID- 1585764 TI - ras gene mutations in Malaysian leukemia patients. PMID- 1585765 TI - Successful treatment with tranexamic acid for severe bleeding in acute promyelocytic leukemia. PMID- 1585766 TI - Combinations of three different forms of alpha-thalassemia in a large Indian family from Durban, South Africa: hematological observations. AB - We have identified three types of alpha-thalassemia in 28 members of an Indian family from Durban, South Africa. The rare South African (SA) type of alpha thalassemia-1, which is characterized by an approximately 23-kb deletion involving the psi zeta, psi alpha 2, psi alpha 1, alpha 2, alpha 1, and theta 1 genes, was present in 13 members [6 simple heterozygotes, 5 with Hb H disease of the --(SA)/-alpha(-3.7 kb) type, and 2 with Hb H disease of the --(SA)/-alpha( 4.2 kb) type]. Seven others were heterozygotes for alpha-thalassemia-2 (-3.7 kb), 1 was homozygous for this deletion, and 1 was a compound heterozygote [-alpha( 3.7 kb/-alpha(-4.2 kb)]. Hematological and hemoglobin composition data indicated a moderate anemia in all 7 patients with Hb H disease with severe microcytosis and hypochromia, no elevation of gamma-chain synthesis, low levels of Hb A2 (0.3 0.7%), and low levels of Hb H. The most severe disease was present in 2 teenagers with the --(SA)/-alpha(-4.2 kb) combination. PMID- 1585767 TI - Tissue plasminogen activator in essential hypertension. PMID- 1585768 TI - Phase I/II study of recombinant human granulocyte-macrophage colony-stimulating factor in patients with advanced malignancy. The Multicenter Study Group. AB - The toxicity and hematologic effects of Escherichia coli-derived recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were studied in 58 treatment cycles in Japanese patients with advanced malignancy as a phase I/II clinical trial. rhGM-CSF in doses from 30 to 250 micrograms/m2/day was administered by 24-hour continuous intravenous infusion, 8-hour intravenous, or a daily subcutaneous injection for 14 days. The most common adverse drug events (ADE) were fever, nausea/vomiting, diarrhea, skin eruption, and phlebitis. The frequency of moderate and severe ADE was 2.9, 14.7, 35.3 and 47.1% at 30, 60, 125, 250 micrograms/m2/day, respectively. In terms of administration routes, the frequency of ADE was 69% with 24-hour continuous intravenous infusion, 39.1% with 8-hour intravenous infusion and 16.7% with subcutaneous injection. Regarding the hematologic effects of rhGM-CSF, leukopenia improved in a dose-dependent manner. The appropriate dose level to be used in the phase II study was estimated to be in the range between 60 and 250 micrograms/m2/day. PMID- 1585769 TI - Marked decline of favism after neonatal glucose-6-phosphate dehydrogenase screening and health education: the northern Sardinian experience. AB - Favism is a potentially fatal manifestation of glucose-6-phosphate dehydrogenase (G6PD) deficiency, and it is therefore a public health problem in areas where this genetic abnormality is common. In the district of Sassari (northern Sardinia), the frequency of G6PD male hemizygotes is approximately 7.5%, and therefore all newborns since 1971 have been screened for G6PD deficiency. We have analyzed the incidence of favism in this community in two 10-year periods: (1) 1961-1970; and (2) 1981-1990. In period 1, there were 508 cases of favism, of which 76% occurred in boys. In period (2) there were 144 cases of favism, of which only 52% in boys. Thus, between the two periods there was an overall decrease in the incidence of favism of 75%, whereas the proportion of girls affected has approximately doubled. These data suggest that neonatal screening and health education programs can produce a substantial decrease in the number of cases of favism, and that the relative increase in favism in girls is possibly due to failure of the screening method used to detect all the heterozygotes for G6PD deficiency. PMID- 1585770 TI - Therapeutic and prognostic value of modal number of chromosomes at the blastic phase of Philadelphia-chromosome-positive chronic myeloid leukemia: comparison based on the same criteria between Nagasaki University and Roswell Park Memorial Institute. AB - In a comparison of 47 patients with Philadelphia-chromosome (Ph)-positive chronic myeloid leukemia (CML) in the Nagasaki University School of Medicine and 64 patients with the same disease in the Roswell Park Memorial Institute, the correlation between the modal number of chromosomes and the therapeutic response and/or survival after the onset of the blastic phase (BP) was evaluated. The patients were divided into four groups on the basis of the modal number of chromosomes of the cells in the bone marrow: those with hypodiploidy (group 1), those with pseudodiploidy carrying a Ph chromosome (group 2), those with 47 chromosomes (group 3), and those with 48 or more chromosomes (group 4). The results revealed similar trends in the two institutes. Namely, the therapeutic response and the survival after the onset of the BP in groups 1 and 4 were more unfavorable and shorter than those in groups 2 and 3, although the former (group 2) had a better prognosis than the latter (group 3). Thus, the statistical analysis revealed that the numerical chromosome findings at the BP are useful parameters for assessing the therapeutic response and survival after the onset of the BP of CML. PMID- 1585771 TI - Mitoxantrone and continuous infusion of cytosine arabinoside in refractory and relapsed acute lymphoblastic leukemia. AB - Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR. PMID- 1585772 TI - Prognostic value of the plasma cell synthesis score in multiple myeloma. AB - The prognostic value of the Plasma Cell Synthesis Score (PCSS) has been tested in a group of 140 patients with multiple myeloma followed up from diagnosis to death. Calculation of PCSS, based on the regression coefficients obtained by multivariate regression analysis according to Cox's model, was performed according to the formula: [formula: see text] Substratification into three risk groups was performed as follows: low risk = PCSS more than 70; moderate risk = PCSS between 50 and 70; high risk = PCSS less than 50. Significant differences were found among the three stages regarding median survivals (p less than 0.005), survival curves (p less than 0.000000001), and response to therapy (p less than 0.00001). A positive significant relationship was demonstrated between calculated PCSS and survival in the whole group (p less than 0.000001). PCSS could be a good estimation of bone marrow plasma cell differentiation, and therefore could be a useful prognostic parameter in multiple myeloma. PMID- 1585773 TI - Massive tissue necrosis can be induced by heparin. PMID- 1585774 TI - Thromboembolic complications in beta thalassemia major. AB - Thromboembolic complications in beta-thalassemia major have seldom been reported and their association with risk factors such as left ventricular failure and postsplenectomy thrombocytosis has remained speculative. In this report we describe 4 patients with unusual thromboembolic manifestations: recurrent arterial occlusion, recurrent pulmonary thromboembolism, venous thrombosis and a fatal cerebrovascular event. Although in all patients both risk factors were present, the precise causes for their thromboembolic complications were not identified. In 1 patient, however, a marked increase in hematocrit following blood transfusion resulted, in all likelihood, in a fatal cerebrovascular infarction. We suspect that these patients (constituting 4% of our beta thalassemic group) represent a subset of those with high susceptibility to both arterial and venous thromboembolic complications. PMID- 1585775 TI - Myeloblastic leukemoid reaction in paroxysmal nocturnal hemoglobinuria associated with myelodysplasia. AB - Paroxysmal nocturnal hemoglobinuria (PNH) has been observed to evolve into myelofibrosis and acute myeloid leukemia. Myeloblastic leukemoid reaction has not been described in PNH. We described a patient with PNH with myelodysplasia and septicemia. The marrow aspirates showed a picture of myeloblastosis which subsided when sepsis was controlled. The myeloblastic leukemoid reaction in our patient related to overwhelming sepsis, splenectomy and overt hemolysis. PMID- 1585776 TI - Lung abscess due to Pseudallescheria boydii in the course of acute leukaemia. Report of a case and review of the literature. AB - We report a case of lung infection by Pseudallescheria boydii, which appeared during therapeutic aplasia in a patient with acute leukaemia. The association of sudden chest pain and fever with negative blood cultures and haemoptysic expectoration first suggested a diagnosis of pulmonary aspergillosis, in particular because evidence of lung abscesses appeared very rapidly and large mycelial filaments were found on direct examination of the expectoration. Pseudallescheria boydii was identified by culture. Investigations in vitro of the effects of antimycotics showed that the micro-organism was resistant to amphotericin B and sensitive to imidazoles. The clinical and radiological outcome after treatment with ketoconazole was favourable. PMID- 1585777 TI - Acquired von Willebrand's disease in association with essential thrombocythemia: regression following treatment. AB - Acquired von Willebrand's disease in a 40-year-old woman affected with essential thrombocythemia (ET) is reported. The profile of plasma von Willebrand factor (vWF) revealed decreased ristocetin cofactor activity and diminished large multimers of vWF in spite of a normal vWF antigen level. There was no evidence of circulating inhibitor against the factor VIII complex. The vWF abnormality improved by controlling the platelet count following treatment for ET with interferon-alpha 2b and ranimustine. The possible mechanism of the development of AvWD in ET is briefly discussed. PMID- 1585778 TI - Pure red cell aplasia following autoimmune haemolytic anaemia. Cell-mediated suppression of erythropoiesis as a possible pathogenesis of pure red cell aplasia. AB - We report here a rare case of pure red cell aplasia (PRCA) following autoimmune haemolytic anaemia (AIHA). After 4 years of AIHA, the patient developed anaemia with severe erythroid hypoplasia and was diagnosed as having PRCA. At this time, Coombs' test was negative and parvovirus infection was not recognized. The patient received azathioprine, and PRCA improved. To determine the pathogenesis of PRCA, in vitro culture studies of erythropoietic and granulopoietic precursors were performed. The patient's serum or IgG did not suppress the colony formation of bone marrow colony-forming units-erythroid (CFU-E) of normal subjects and the patient. In contrast, mononuclear cells in the peripheral blood of the patient significantly suppressed CFU-E of normal subjects. Media conditioned by the patient's mononuclear cells did not significantly suppress CFU-E. The significant production of suppressive cytokine such as tumour necrosis factor or gamma interferon by the patient's mononuclear cells was not recognized. These findings suggest that the cytotoxic mononuclear cells affected directly the erythropoietic precursors and caused PRCA in this patient. The pathogenesis of PRCA was, therefore, considered to be different from that of the preceding AIHA. PMID- 1585779 TI - [Clinical aspects and diagnosis of cerebral hemorrhage]. AB - Primary intracerebral hemorrhages are often dramatic and lethal. Therapeutic possibilities are limited. Multivariate studies show that patient age, hematoma volume, ventricular extension of the hemorrhage, and level of consciousness are the decisive prognostic parameters. This overview shows that the etiological spectrum is larger than suggested by the classic paradigm of "either hypertensive or cryptic angioma". The variability of clinical presentation can be put into a systematic order by means of clinical neurological examination and imaging techniques. Experiences with 62 consecutive cases from the Klosterneuburg Stroke Data-Bank are reported. PMID- 1585780 TI - [Preclinical management of patients with intracerebral hemorrhage]. AB - The prehospital treatment of patients with intracerebral hemorrhage must be aimed at prevention of secondary brain damage and provision of an optimal physiologic environment to maximize the potential of recovery. Adequate cerebral oxygenation and the prevention of hypercarbia is a priority. This can only be managed by early intubation and artificial ventilation in patients with a Glasgow-coma-scale below eight, together with the restoration of normal hemodynamics to guarantee adequate cerebral perfusion. PMID- 1585781 TI - [Intensive care of cerebral hemorrhage]. AB - Critically ill patients with intracerebral hemorrhage require immediate treatment in an intensive care unit. In the acute phase of the disease the patients are endangered from increased intracerebral pressure, respiratory disorders (aspiration!) and hypertension. An adequate intensive care management consisting of sedation, analgesia, intubation and mechanical ventilation, correct body positioning and treatment of hypertension is of decisive importance for the prognosis of these patients. The aim of this report is to discuss the most important therapeutic strategies and arising problems in the course of intracerebral hemorrhage. PMID- 1585782 TI - [Intracerebral hemorrhage from the neurosurgical viewpoint]. AB - After the introduction of computed tomography intracerebral haemorrhage (ICH) was diagnosed more frequently. We discuss the role of surgical strategies for treatment of ICH of different aetiology. The main factors for surgical intervention for ICH (except vascular malformations) are: degree of midline shift, deformation of neurological deficit or consciousness-level and ventricular enlargement. In small hematomas surgical evacuation is of no benefit for final outcome. PMID- 1585783 TI - [Problems of long-term therapy with anticoagulants]. AB - Oral anticoagulants are highly effective for the prevention of recurrence of venous thromboembolism and of thromboembolic complications in rheumatic and non rheumatic atrial fibrillation, dilated cardiomyopathy and in patients with prosthetic heart valves, but less effective for prevention of arterial thrombosis. Bleeding is the main side effect, the risk of fatal bleeding is 0.2 to 0.4% per year, depending on the intensity of treatment. The problem of the standardization of the prothrombin time determination has been solved by the introduction of the international normalized ratio. Recent studies have shown that a lesser degree of anticoagulation (INR 2.0 to 3.0) is sufficient to prevent venous thromboembolism and cardiac emboli. The measurement of activation markers of coagulation will probably allow a more rational monitoring in the near future. PMID- 1585784 TI - [Differential diagnostic considerations in eosinophilia with reference to a 19 year-old patients with Loffler endocarditis]. AB - In this case report a 19-year-old girl suffering from hypereosinophilia with 3500 cells/mm3 and involvement of the right lung, lymph nodes, skin, serosa and heart is described. Within 10 days of admission an infiltration of the right upper lung lobe disappeared spontaneously and was diagnosed as transient eosinophilic lung infiltration according to Loffler. Both lymph node needle biopsy and several skin biopsies revealed merely general reactive changes whereas a bronchial lavage produced a significant number of eosinophilic granulocytes. Autoimmunologic or infectious-toxic disorders were ruled out as etiologic causes. Within 4 weeks after admission severe mitral and tricuspidal insufficiency as well as AV-block second grade and protodiastolic galloping rhythm developed in addition to progressing polyserositis. The echocardiographic pattern was in accordance with restrictive endocarditis. Due to the greatly reduced left ventricular ejection fraction cortisone (125 mg prednison equivalent) was tentatively administered as therapy. Within 2 weeks heart-, serosa- and lymph-node-findings became normal as well as the eosinophilic count, the scaling skin rash being only partly improved. After 10 months of continuous cortisone therapy (10 mg prednison equivalent) the patient was without evidence of disease. However in conclusion, it may be said that such pattern of findings suggests a hypereosinophilic syndrome with Loffler endocarditis with an unknown future course of disease although generally survival prognosis may not be too high. PMID- 1585785 TI - Immunocytochemical localisation of transferrin in the human brain. AB - Immunocytochemical studies on the adult human brain have shown that transferrin is localized within three main compartments in the adult human brain. Oligodendrocytes and some astrocytes together with cells of the choroid plexus showed the highest intensity of staining. Neuronal staining occurred mainly within pyramidal or large polygonal cells, but this showed considerable regional variation being most marked in areas such as the cerebral cortex, amygdala, hippocampus, brainstem and cerebellar Purkinje cells. Small neurones such as caudate interneurones and granule cells showed relatively low activity. Diffuse immunostaining of the neuropil was evident, particularly where heavy neuronal or glial staining occurred. Immunostaining was also observed in white-matter fibre tracts. This pattern of distribution helps to provide a model for the mechanisms responsible for iron homeostasis in the normal brain. PMID- 1585786 TI - Postnatal development of the rabbit pineal gland. A light- and electron microscopic study. AB - The development of the rabbit pineal gland has been studied by light and electron microscopy from the 1st to the 120th postnatal day. After 24 h of postnatal life, the pineal parenchyma is highly cellular, showing two identifiable cell types: pinealocytes I and II. Immature type II pinealocytes arrange either in cellular cords or clusters or forme rosette-like structures. At the 5th postnatal day, corticomedullar differentiation is established. Rosette-like structures and cellular cords are absent from the cortex. Along the postnatal period, nuclei of pinealocytes are set apart due to cytoplasmic widening and development of cell processes. These structures pervade the cellular cords and rosette-like structures formed by immature type II pinealocytes. Rosette-like structures are no longer seen beyond the 30th postnatal day, and cords of type II pinealocytes from the 90th postnatal day on. At this time, the rabbit pineal gland is considered to be histologically mature. PMID- 1585787 TI - Blood vasculature of the lymph node in the dog: anatomical evidence for participation of extrahilar arterial vessels in the blood supply of the cortex. AB - The organization of the arterial vessels of dog lymph nodes (LN) was studied using methods of visualization of the vasculature by systemic injection of different tracers (colloidal carbon, Micropaque resin and methylmethacrylate) followed by observation of the samples by light microscopy (after clearing of the thick sections of LN) or scanning electron microscopy (corrosion casts). LN from all of the three groups of nodes studied (tracheobronchial, paratracheal and popliteal) showed an extensive network of arterial vessels encircling the capsule of the organ. We found that branches of these capsular arteries penetrated deeply into the cortical domain of LN. The capsule-originating vessels appeared to have a significant participation in the blood supply of the LN parenchyma at the cortical domains of the organs. Our findings are in contrast with current views on the angiology of the LN that consider that virtually all of the arterial capillaries of the LN parenchyma come from hilar arteries. We propose, therefore, that important segments of the LN cortex receive their blood supply from capsular arteries rather than from hilar vessels. PMID- 1585788 TI - Calcitonin gene-related peptide-like immunoreactivity in the human small intestine. AB - Calcitonin-gene-related-peptide (CGRP)-like immunoreactivity was localized in nerve fibres, neuronal somata and in mucosal endocrine cells of the human small intestine. Immunoreactive enteric neurons were more numerous in the submucous plexuses than in the myenteric plexus. Morphologically, they predominantly had the appearance of type II neurons. The majority of the CGRP-like immunoreactive nerve fibres ran within the ganglionic nerve plexuses. Only a small proportion could be observed in the lamina propria, the lamina muscularis mucosae, or the circular and longitudinal outer smooth muscle layer. These findings suggest that within the wall of the human small intestine neuronal CGRP of either extrinsic or intrinsic origin exerts its effect chiefly on other enteric neurons, and might be indirectly involved in the regulatory functions of the human small intestine. PMID- 1585789 TI - Microvascularization of the rat superior cervical ganglion. A three-dimensional observation. AB - The three-dimensional image of the microvascularization of the rat superior cervical ganglion (SCG) was examined using the vascular corrosion cast technique in conjunction with scanning electron microscopy. It was found that the rat SCG was a highly vascularized organ. Arteries supplying the ganglion gave rise to a subcapsular capillary plexus before branching off to become intraganglionic capillaries. Two types of intraganglionic capillaries, large and small, were observed throughout the organ. Numerous anastomoses among these capillaries were found before they converged into venules and collecting veins. However, a pattern of blood vessels resembling portal-like intraganglionic microcirculation could not be demonstrated. PMID- 1585790 TI - High-resolution scanning electron microscopic study of the mouse submandibular salivary gland. AB - The submandibular gland of the mouse was studied by high-resolution scanning electron microscopy, using the osmium-dimethylsulfoxide-osmium method. The three dimensional structures of the intracellular membranous organelles of acinar cells were clearly revealed. The luminal surface of cisterns of the granular endoplasmic reticulum and Golgi apparatus exhibited particles of 8-15 nm in diameter. The secretory canaliculi presented short microvilli which were irregularly arranged. The striated duct cells were characterized by rich mitochondria arranged vertically in the basal portion. The lamellar mitochondrial cristae were noted in three-dimensional images. The luminal surface extended short microvilli, while that of the excretory duct cell presented complicated microplicae. The capillary endotheliocytes showed a few short microvilli, and their fenestrated areas were bordered by cytoplasmic crests. Fenestrae were 50-80 nm in diameter and showed a plug in their center. The basement membranes of the acini and capillaries showed a spongy structure with various strands and meshes. Collagenous fibrils crisscrossed on their surface. PMID- 1585791 TI - Sectorial angioarchitecture of the human tibia. AB - The blood supply of the periosteum of the human tibia was investigated by anatomical dissection of 12 lower extremities which were filled with injection mass. By division of the tibia into 4 segments (proximal and distal fifths; proximal and distal diaphysis) a general supplying system of the periosteum was found. The proximal fifth of the tibial periosteum is nourished by branches of the arteriae recurrentes tibiales anterior et posterior and the aa. inferiores medialis et lateralis genus. At the proximal diaphysis (next three tenths of the tibia) periosteal branches arise from the aa. tibialis anterior and posterior, whereas the distal diaphysis is nourished exclusively by semicircular vessels of the a. tibialis anterior which twine around the bone and merge with each other at the facies medialis. Concerning the periosteal blood supply of the distal fifth of the tibia, two different types were found. In two thirds of the cases the lateral side was nourished by branches of the a. tibialis anterior, which are supported by vessels from the a. fibularis. In one third the latter branch was absent so that the rami periostales arising from the a. tibialis anterior nourished the lateral aspect of the distal tibia alone. The dorsal region was supplied in all cases by rami of the a. fibularis and a. tibialis posterior. On the medial side the periosteal nourishment is ensured only by anastomosis. Branches of the a. tibialis anterior supply the facies lateralis and facies posterior where it is supported by vessels of the a. tibialis posterior and in a minor region of rami of the a. fibularis (distal) and a. poplitea (proximal).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585792 TI - Distribution of synaptic boutons in the mesencephalic trigeminal nucleus of the rat--a quantitative electron-microscopical study. AB - The distribution of synapses and synaptic bouton types in the mesencephalic trigeminal (Me5) nucleus was examined in a quantitative electron-microscopical study. Of 588 terminal boutons that were counted in the compact caudal part of the Me5 nucleus, less than 8% formed synapses on the somata of the predominantly unipolar Me5 neurons. About 79% formed synapses on fibres located between the Me5 somata, while about 13% of the vesicle-containing terminals had no clear synaptic specialization. All of these non-synaptic terminals were G type boutons, with pleomorphic and large characteristic dense-core vesicles. Approximately 60% of the axosomatic synapses were of the S type, containing spherical vesicles and an asymmetrical or symmetrical synaptic specialization. About 20, respectively 15% of the axosomatic synapses, were of the F, respectively P type; both are symmetrical synapse types containing either a majority of flat or pleomorphic vesicles. Less than 10% of the axosomatic synapses were of the G type. Although some proportional differences were noted, an almost similar bouton type distribution pattern was found for the axodendritic synapses suggesting that the axosomatic and axodendritic synapses in the Me5 nucleus are part of the same afferent fibre plexus covering the Me5 nucleus. PMID- 1585793 TI - Vasoactive intestinal polypeptidergic innervation and gastroenteropancreatic system: an immunocytochemical study in the hedgehog Erinaceus europaeus. AB - The pattern of the digestive vasoactive intestinal polypeptide (VIP)-ergic innervation is described immunohistochemically in the hedgehog Erinaceus europaeus. This animal is a small-sized, wild, nocturnal, lower eutherian mammal whose gastrointestinal tract shows some similarities with the avian gut. The myenteric plexus of the stomach, the mucosa of the small intestine and the circular muscle layer of the large intestine are the best VIP-innervated structures. The pattern of the positive innervation is similar to that described in other mammals and in some bird species. The widespread diffusion of the neuropeptide in the gut is probably due to the importance of its functions in the digestive physiology. PMID- 1585795 TI - Oxcarbazepine does not interact with cimetidine in healthy volunteers. AB - When cimetidine (CIM) is administered together with the anti-epileptic drug carbamazepine (CBZ), a drug interaction may cause a rise in plasma concentrations of CBZ, which can result in CBZ-related toxic symptoms. The aim of this cross over study was to investigate whether CIM influences the disposition and kinetics of the new anti-epileptic oxcarbazepine (OXC) and its metabolites. In 8 healthy volunteers there was no difference in AUC, Cmax or tmax when OXC was administered either with or without CIM. The results of this study suggest that in the treatment of epilepsy OXC offers an important advantage over the established anti epileptics, especially when concomitant therapy with CIM is required. PMID- 1585794 TI - Myasthenia gravis muscle antibodies examined by ELISA: IgG and IgM antibodies characterize different patient subgroups. AB - Sera from 90 myasthenia gravis (MG) patients were examined for antibodies against skeletal muscle citric acid extract (CA) antigens by ELISA and indirect haemagglutination (IHA). 31% (ELISA) and 24% (IHA) of the sera were positive, and the results of the two tests were in good agreement. 18 of 28 patients positive in ELISA had IgG CA-antibodies, 10 had IgM and 3 IgA CA-antibodies. The patients with IgG antibodies had a high mean age of MG disease onset, and 9/14 thymectomized patients had a thymoma. Patients with IgM CA-antibodies had a much lower age of onset and 4/5 thymectomized patients had thymus hyperplasia. IgM antibody positive patients had a long disease duration, indicating that they produce IgM antibodies for an indefinite period of time without switching to IgG antibody production. PMID- 1585796 TI - A descriptive study of epilepsy in the district of El Salvador, Chile, 1984-1988. AB - To describe the epidemiological characteristics of epilepsy in a northern area of Chile, an investigation was conducted in four localities in the province of Copiapo (population of 17,694). Based on 314 cases of active epilepsy, the prevalence per 1000 at June 30, 1988 was 17.7. The average annual incidence for the period 1984-1988 was 113 per 100,000. Partial seizures were the most frequent type of seizure diagnosed (54.1%). Antecedents considered as possible etiological factors were found in 29.9% of cases. According to age of onset, 64.6% had their first attack before 15 years. Middle and low socioeconomic classes had higher prevalence rates of epilepsy. We compare our results with previous Latin-American studies. PMID- 1585797 TI - HLA-linked spinocerebellar ataxia: a clinical and genetic study of large Italian kindreds. AB - Five families with late onset autosomal dominant spinocerebellar ataxia, were studied. Linkage between the disease and HLA loci on the short arm of chromosome 6 was shown in the two largest pedigrees. Clinical study of 26 patients and neuropathological study in one are reported. The disease was characterized by cerebellar and pyramidal involvement variably associated with cranial nerve and peripheral nervous system disorders. A remarkable concordance of the main clinical features was observed in patients with similar disease duration. Comparison with previous reports of HLA-linked spinocerebellar ataxia kindreds showed differences in clinical phenotypes. Although these might be due to genetic variation, the hypothesis is suggested that the phenotype might appear more homogeneous if disease duration is taken into account. PMID- 1585798 TI - Regional cerebral blood flow after long-term exposure to carbon disulfide. AB - Sixteen former rayon viscose workers were investigated four years after the exposure to carbon disulfide was discontinued. Median age was 58 years (range 43 65 years), median exposure time was 17 years (range 10-35 years). Encephalopathy was diagnosed in altogether 14 workers. To further explore pathophysiological mechanisms, cerebrovascular investigations were employed. Doppler ultrasound examination of the precerebral vessels in 15 workers showed a slight stenosis of the left internal carotid artery in one. Regional cerebral blood flow investigation (rCBF) with single photon emission computerized tomography (SPECT) with Xenon-133 gas was performed in 14. There was no significant difference from a control group. Regional side-to-side asymmetries beyond reference limits were demonstrated in eight workers. The abnormalities were modest, but may indicate a tendency toward focal blood flow disturbances in workers with long-term exposure to carbon disulfide. PMID- 1585799 TI - Vitamin B12 in CSF: reduced CSF/serum B12 ratio in demented men. AB - Vitamin B12 concentrations were determined in serum and cerebrospinal fluid (CSF) of 32 controls and 102 patients with dementia. The dementias were classified as Alzheimer's disease (AD), senile dementia of Alzheimer type (SDAT) and multi infarct dementia (MID). A substantial number of patients (n = 42) could not be assigned to any of these diagnostic groups, as their dementias were of non AD/SDAT and non-MID types. They were instead assigned to a group called non ultra descriptum (NUD). CSF B12 correlated significantly with serum B12. There were no statistically significant differences in serum B12 levels between the groups. Although with considerable overlap, CSF B12 concentrations and CSF/serum B12 ratios were significantly lower in the NUD group than in the control group. The NUD group had significantly lower CSF/serum B12 ratios than the group of patients with AD/SDAT. There was significant male predominance in the group of demented patients that had low CSF/serum B12 ratios outside the bivariate reference region. CSF and serum B12 levels appear insufficient as measures of the true brain vitamin B12 status. It may be a more dynamic approach to use the CSF/serum B12 ratio as an indication of transport function across the blood brain barrier, and possibly also across the CSF brain cell barrier. PMID- 1585800 TI - Influence of erythrocyte aggregability and plasma fibrinogen concentration on CBF with aging. AB - The influence of the rheological properties of the blood on cerebral perfusion is still unresolved. Data on normal subjects are lacking and difficulties arise regarding the effect of blood viscosity owing to its close relationship with hematocrit. For these reasons we have studied the relationship between two rheological hematocrit-independent parameters and CBF in normal subjects of various ages. 36 normal volunteers, aged 20-74, free from risk factors, have been studied. CBF was measured by the Xenon inhalation method. Erythrocyte aggregability was expressed as Mean Erythrocyte Aggregation Index (MEA). Plasma fibrinogen concentration was evaluated by the coagulative method in 26 subjects. No correlation was found between CBF and MEA or fibrinogen in the subjects under the age of 45. A significant negative correlation was found between CBF and MEA (p = 0.015) and between CBF and fibrinogen (p = 0.011) in the subjects over 45. These data show that cerebral perfusion is influenced by the rheological properties of the microcirulation only with aging. We suggest that a "rheological autoregulation" exists and that it works properly in youth, only to be lost with physiological aging. This finding can be of significance in the pathogenesis of cerebrovascular disease processes in humans. PMID- 1585801 TI - Mood disorder in a group of self-cutting adolescents. AB - This study describes the occurrence of mood disorder in a group of adolescent inpatients involved in self-cutting behavior. Although self-cutting is generally said to be associated with borderline personality disorder, a substantial number of patients who cut themselves in our study were clinically depressed. In addition, the self-cutting adolescents had a high prevalence of child abuse, past psychiatric history, and family psychiatric history. The incidents tended to spread by contagion and occur at times of change affecting the milieu. Clinical implications of these findings are discussed. PMID- 1585802 TI - Relaxation therapy reduces anxiety in child and adolescent psychiatric patients. AB - The immediate effects of relaxation therapy (RT) were assessed in 40 hospitalized children and adolescents with diagnoses of adjustment disorder and depression. These effects were assessed using a within subjects pre-test/post-test design and by comparison with a control group of 20 depressed and adjustment disorder patients who watched a 1-h relaxing videotape. The 1-h RT class consisted of yoga exercise, a brief massage and progressive muscle relaxation. Decreases were noted in both self-reported anxiety and in anxious behavior and fidgeting as well as increases in positive affect in the RT but not the video group. In addition, adjustment disorder patients and a third of the depressed patients showed decreases in cortisol levels following RT, while no changes were noted in the video group. Thus, both diagnostic groups appeared to benefit from the RT class. PMID- 1585803 TI - Epidemiological study of children institutionalised for psychiatric disorders. AB - A cross-sectional and longitudinal epidemiological study of children institutionalised for psychiatric disorders has been carried out. The differences of discharge distribution allows to describe an entanglement of three differents logics: the medical logic: diagnostic (Emotional and conduct disorder, Mental retardation, Psychosis), etiological organic factors, associated somatic disorder. the social logic: father's occupational level and etiological environnemental factors. the institutional logic: child's age when admitted, institutional categories. PMID- 1585804 TI - A comparison of medicated and nonmedicated attention-deficit disordered hyperactive boys. AB - Sixty boys diagnosed as having attention-deficit disorder with hyperactivity were divided into two equal groups, depending on whether or not they were taking medication for their disorder. These two groups were subdivided equally into younger and older groups, the cutoff being 11.5 years. All subjects were given the Children's Depression Inventory, the Coopersmith Self Esteem Inventory and the Children's Attributional Style Questionnaire. Teachers completed the Child Behaviour Checklist and Conners' Teacher Rating Scale. The results indicated that in the older subjects, the medicated group had lower social self-esteem than the nonmedicated group and in younger subjects the medicated group had higher academic self-esteem than the nonmedicated group. There were no significant differences among the groups with respect to depression; all four groups of subjects were mildly depressed. The younger subjects in general were more inattentive, nervous, impulsive and aggressive; and teachers did not report any less externalising behaviour in those subjects who were on medication. These results were interpreted in the light of findings from previous studies, and the lack of drug effect on externalising behaviour is discussed. Clinical recommendations are made for alleviating depression and improving self-concept by means of cognitive therapy, especially for older medicated ADDH children. PMID- 1585805 TI - Children's symptoms and items of behaviour. An epidemiological study of sociocultural aetiology. AB - The aim of this article is to present the results from a point-prevalence study of symptoms and items of behaviour among children and adolescents in the western part of Norway. Empirical manifestations of personality traits and psychopathology in the ordinary population are factor-analysed. The prevalences in different types of local communities are calculated, and the variations are discussed using the concept of socialization, especially development and internalization of values, norms and behaviour in cultures with different rates of change. PMID- 1585806 TI - Characterizing the fundamental social handicap in autism. AB - The social impairments of autism, which are especially salient in autism of the Asperger type, have been attributed to a failure of affective processing, and more recently to a failure to develop a "theory of mind". Recent research evidence bearing on these theories is reviewed and a new hypothesis is put forward, based on research in progress, which posits a developmentally earlier abnormality of the "social gaze response": the inherent tendency of the normal infant to focus gaze and attention on social cues and, later, on objects in the environment as indicated by the gesture of gaze of others. Weakness or absence of the social gaze response is enough, it is argued, to account for many of the typical symptoms of autism, including the failure to acquire a theory of mind. PMID- 1585807 TI - The treatment of children with obsessive-compulsive disorder. AB - Very little is known about the treatment of children with an obsessive-compulsive disorder (OCD). No controlled studies have been conducted into the effects of behaviour therapy or other kinds of psychotherapy. There have only been three studies into the effects of antidepressants. After providing some general information on OCD, this article discusses the possibilities, effects and some of the difficulties of treatment. PMID- 1585808 TI - Clinical picture, dynamics and treatment of reactive depressions in infant. AB - The authors studied the typology, clinical picture, dynamics and therapy of reactive (psychogenic) depressions in 46 children, aged 1.5-4.5 years. Clinical psychopathological variants of depression and types of dynamics have been described, which is important for prognosis and choice of adequate therapy. PMID- 1585809 TI - Subcutaneous and skeletal muscle vascular responses in human limbs to lower body negative pressure. AB - Cardiopulmonary baroreceptor unloading in humans comparably increases sympathetic discharge to skeletal muscle in the forearm and calf, but blood flow studies have disclosed differential rather than uniform vasomotor responses in the extremities. The aim of the present study was to address the issue of differential effects of orthostatic stress on forearm and calf vascular adjustment and to extend previous studies by determining changes in vascular responses separately in various vascular beds of the limbs. The local [133Xenon] washout method was used for recording blood flow rates in subcutaneous tissue and skeletal muscle. Simultaneous recordings from the forearm and calf were performed in 11 healthy young males during lower body negative pressure at -10 mmHg. Heart rate, arterial mean and pulse pressures did not change during lower body negative pressure. In the forearm blood flow rates decreased significantly, in subcutaneous tissue by 16 +/- 2% (mean +/- SEM) and in skeletal muscle by 16 +/- 1%. In the calf lower body negative pressure induced a significant decrease in blood flow rates of 17 +/- 3% in subcutaneous tissue and of 30 +/- 2% in skeletal muscle. This vasoconstriction in calf skeletal muscle was consistently disclosed in both legs and was about the same magnitude in each calf when studied with the one leg exposed to lower body negative pressure and the other outside the lower body negative pressure chamber. These findings suggest that during unloading of cardiopulmonary afferents, reflex sympathetic activation as an important autonomic adjustment to orthostatic stress is accompanied by uniform vasoconstriction in subcutaneous and skeletal muscle vascular beds of human limbs. PMID- 1585810 TI - Captopril and time dependent changes in post- to pre-glomerular resistance ratios in remnant kidneys of pre-hypertensive rats. AB - Micropuncture experiments were performed on intact and remnant kidneys of male Sprague-Dawley rats before and after angiotensin converting enzyme inhibition with captopril (0.5 mg kg-1 iv). Partially nephrectomized rats were studied at 2 and 8 weeks post-surgery before the development of systemic hypertension. At 2 weeks, nephrectomized rats had a numerically higher tubular stop-flow pressure than controls (43 +/- 2 mmHg vs. 38 +/- 2 mmHg; P = 0.08) and a higher post- to pre-glomerular resistance ratio (Re/Ra) (0.40 +/- 0.03 vs. 0.31 +/- 0.03; P = 0.08). At 8 weeks, stop-flow pressure and post- to pre-glomerular resistance ratios were similar in remnant and intact kidneys. Captopril had no effect on stop-flow pressure in 2 week post-surgery nephrectomized rats or either control group, but it increased stop-flow pressure in 8 week post-surgery nephrectomized rats (40 +/- 2 to 44 +/- 2 mmHg, P = 0.04). This increase in stop-flow pressure was associated with an increase in the post- to pre-glomerular resistance ratio (0.33 +/- 0.02-0.42 +/- 0.02, P = 0.009). Stop-flow pressure was positively correlated with the post- to pre-glomerular resistance ratio in 2-week post surgery nephrectomized rats and their respective controls when combined (r = 0.89, P = 0.0001) and 8-week post-surgery nephrectomized rats and their respective controls combined (r = 0.78, P = 0.0001). Stop-flow pressure was not significantly correlated with mean arterial pressures or welling-point pressures in these groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585811 TI - Dopamine receptor blockade and synthesis inhibition during exaggerated natriuresis in spontaneously hypertensive rats. AB - The influence of dopamine receptor blockade and synthesis inhibition on natriuresis induced by isotonic saline volume expansion was investigated in anaesthetized spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The aim of the study was to elucidate the mechanisms underlying the phenomenon of exaggerated natriuresis during volume expansion that has been observed in spontaneously hypertensive rats. Volume expansion, at 5% of body weight, resulted in a larger and faster natriuretic response in spontaneously hypertensive rats than in Wistar-Kyoto rats. Sixty minutes after commencement of volume expansion the natriuretic response (accumulated sodium excretion) in Wistar-Kyoto rats (n = 8) was only 24% of that in spontaneously hypertensive rats (n = 17). When spontaneously hypertensive rats were pretreated with the dopamine receptor blockers haloperidol (n = 14, 1 mg kg-1), SCH23390 (n = 8, 30 micrograms h-1 kg 1) or the dopamine synthesis inhibitor benserazide (n = 8, 50 mg kg-1; n = 5, 100 mg kg-1), the natriuretic response to volume expansion was only 16, 35, 59 and 42%, respectively, of that in untreated SHR. The corresponding proportion in the haloperidol-treated (n = 8) compared with untreated Wistar-Kyoto rats was 22%. In conclusion, isotonic volume loading results in more pronounced natriuresis in spontaneously hypertensive than in Wistar-Kyoto rats. Dopamine receptor blockade and synthesis inhibition attenuate the expansion of exaggerated natriuresis in spontaneously hypertensive rats and reduces the volume expansion natriuresis in Wistar-Kyoto rats, indicating that the dopamine system plays an important role. PMID- 1585812 TI - Myogenic vasoconstriction in the rat kidney elicited by reducing perirenal pressure. AB - Autoregulation of renal blood flow is generally believed to result from tubuloglomerular feedback and/or a vascular myogenic mechanism, but there is no consensus on the relative importance of these mechanisms. We designed an experiment in which tubuloglomerular feedback would tend to oppose a myogenic response: the denervated kidney in situ was enclosed in an airtight chamber and exposed to a 35 mmHg subatmospheric pressure for 1 to 10 minutes. Renal blood flow recorded by an electromagnetic flowmeter fell by 33% in the course of a few seconds. Renal venous concentration of inulin showed no consistent change, indicating similar reduction in glomerular filtration rate. Since urine flow also fell, it is likely that the tubular flow rate was reduced. The kidney volume expanded by 10-20%, and subcapsular interstitial fluid pressure was reduced from 6.8 to -8.6 mmHg. Arterial pressure remained unchanged, while renal venous pressure inside the chamber fell from 9.4 to 5.8 mmHg. Normalization of perirenal pressure gave rapid normalization of all parameters. Elevation of ureteral pressure attenuated or even prevented the renal blood flow reduction. Renal decapsulation or sympathetic blockade by phentolamine, or infusion of furosemide or 0.9% NaCl to inactivate tubuloglomerular feedback, did not prevent the renal blood flow reduction. We interpret the results to indicate that myogenic vasoconstriction greatly overpowered TGF and even surpassed the constriction predicted by a mathematical model based on maintenance of the preglomerular wall tension as estimated from transmural pressure. PMID- 1585813 TI - Trophic effects of hypophyseal hormones on resistance vessels and the heart in normotensive and renal hypertensive rats. AB - Arterial pressure is an important determinant of cardiovascular structure and relates positively to it. The purpose of this study was to determine whether pituitary hormones influence the relation of pressure and structure. Male Sprague Dawley rats, aged 5 weeks, were studied in three groups: the first underwent hypophysectomy; the second was hypophysectomized but received replacement therapy with growth hormone and thyroxine; the third served as controls. Four days later half of each group underwent unilateral renal artery clipping, the other half serving as normotensive controls. For 5 weeks estimates were made of systolic blood pressure, heart rate, body weight and plasma renin activity. Rats were then killed; left ventricular, kidney and adrenal weights were determined and, using hindquarter perfusion, estimates were made of resistance at maximal dilatation (reflecting inner radius), and of maximal pressor response (reflecting wall thickness). RESULTS: (1) Hypophysectomy in non-clipped rats reduced growth rate, systolic blood pressure and heart rate while plasma renin activity rose. As related to pressure and to body weight, resistance at maximal dilatation, maximal pressor response, left ventricular weight remained at the juvenile values of a 5 week-old rat. Hormone replacement restored values to those of control rats aged 11 weeks. (2) Clipping in the control group rats increased systolic blood pressure more than in hypophysectomized and growth hormone and thyroxine receiving hypophysectomized groups even though plasma renin activity remained higher in hypophysectomized than in control rats. Plasma renin activity was highest in hypophysectomized rats with highest pressure. (3) Systolic blood pressure related positively to left ventricle weight, resistance at maximal dilatation, maximal pressor response and calculated wall thickness to inner radius ratios in all groups. However, these regressions were all, like renal structural adaptation, considerably depressed in the hypophysectomized group. Hormone replacement restored the relation of structure and pressure towards that of control group rats. Thus, growth hormone and thyroxine influence maturation of the normal cardiovascular system and greatly enhance its structural upward resetting in hypertension. PMID- 1585814 TI - Reflex changes in post- and preganglionic sympathetic adrenal nerve activity and postganglionic sympathetic renal nerve activity upon arterial baroreceptor activation and during severe haemorrhage in the rat. AB - The aim of the study was to compare pre- (pre-aSNA) and postganglionic adrenal sympathetic nerve activity (post-aSNA) and postganglionic renal sympathetic nerve activity (rSNA) in rats during arterial baroreceptor activation and haemorrhage. Adrenal multifibre nerve activity was recorded in chloralose-anaesthetized Wistar rats. To test for pre-aSNA or post-aSNA in adrenal nerves, a ganglionic blocker, trimethaphan (10 mg kg-1), was administered i.v. If the nerve activity in the adrenal nerve decreased or increased the nerve was considered to contain predominantly post- or preganglionic fibres, respectively. In contrast, the renal nerves exhibit an almost pure postganglionic activity. Baroreceptor activity was tested by activation of baroreceptors, with an alpha-receptor agonist, phenylephrine, which was slowly infused (0.5-2 micrograms kg-1 min-1), and to deactivate the baroreceptors the rats were bled down to 50 mmHg for 8 min. The experiments showed that all tested nerve types were baroreceptor dependent. There were no significant differences between the slopes relating nerve activity inhibition to increase in blood pressure (infusion of phenylephrine). During maximal inhibition there was a difference between the rSNA and pre-aSNA, 87 +/- 4%, n = 6, and 68 +/- 6%, n = 10 (P less than 0.01) of the control value, respectively. The maximal inhibition of post-aSNA was 80 +/- 3%, n = 7, of the control value. During haemorrhage there was a difference between the nerve populations. Pre-aSNA responded with a marked increase within 1.5 min (159 +/- 29% of control, n = 7) and was then maintained at that level until retransfusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585815 TI - Characteristics of the carotid baroreflex in man during normal and flow restricted exercise. AB - Eight subjects were studied in the supine position at rest, during normal dynamic leg exercise (control exercise) and with blood-flow restriction in the working legs (flow-restricted exercise). Graded muscle blood-flow restriction was accomplished by applying a supra-atmospheric pressure of 50 mmHg to the working legs. During incremental-load exercise, flow restriction reduced exercise performance and peak heart rate by 36% and 13%, respectively. The function of the cardiac branch of the carotid baroreflex was studied over its full operational range, at rest and during constant-load control and flow-restricted exercise, by measuring R-R intervals during application of pulse-synchronous graded pressures (40 to -65 mmHg) in a neck-chamber device. Heart rate and arterial pressure were higher during flow-restricted than control exercise, indicating that the flow restriction activated the muscle chemoreflex. Raising the carotid transmural pressure (systolic arterial pressure minus neck-chamber pressure) was accompanied by increasing R-R intervals in all conditions. The set point (point of baseline carotid transmural pressure and R-R interval) coincided with the midportion of the pressure-response curve at rest and with the threshold point of the curve during exercise. The maximal rate of change in relative R-R intervals and the corresponding carotid transmural pressure range were higher during control exercise than at rest and highest during flow-restricted exercise, indicating that exercise and especially flow-restricted exercise increased carotid baroflex sensitivity, and shifted the carotid baroreflex optimal buffering range to higher pressures. The results suggest that the carotid baroflex attenuates exercise heart rate increases mediated by the muscle chemoreflex and/or by central command. PMID- 1585816 TI - Influence of impulse pattern on noradrenaline release from sympathetic nerves in cerebral and some peripheral vessels. AB - Earlier findings suggested that the physiological firing rate in sympathetic nerves did not exceed 10 Hz. Later recordings have revealed that this is a net value: impulses are usually not continuous but occur in bursts of high frequencies separated by quiet periods. The effects of continuous and burst-like neurogenic activation in various isolated blood vessels were compared. In the first part of the study changes in vascular tone were registered. Electrical field stimulatory parameters were chosen to give tetrodotoxin-blockable, neurogenic responses. From dose-response experiments in rat caudal artery a net frequency of 6 Hz was chosen, for bursts usually designed as 30 Hz during 0.2 s followed by a quiet period of 0.8 s. In the rabbit ear artery the neurogenic contraction was enhanced by a mean of near 50% during stimulation with bursts. Now appeared a minor phentolamine-resistant portion, which was not due to release of NPY, 5-HT, histamine or ATP. Also in the rat caudal artery and monkey pial artery a significant enhancement of contraction was seen during burst simulation, whereas in the rabbit facial vein no significant difference in dilatation through beta-receptor activation was obtained. In vessels that do not normally respond with purely neurogenic contractions/dilatations during continuous stimulation, like pial arteries from the rat and rabbit, not even bursts revealed a neurogenic response. In a second series of experiments the influence of continuous and burst like nerve activation on the release of [14C]noradrenaline was studied in monkey, rabbit and rat pial arteries, rat caudal artery and rabbit central ear artery and facial vein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585817 TI - Calcium fluxes in rat thyroid FRTL-5 cells. Evidence for a functional Na+/Ca2+ exchange mechanism. AB - The effect of extracellular Na+ on cytosolic free Ca2+ and on influx and efflux of Ca2+ was investigated in FRTL-5 thyroid cells. Stimulating the cells with the purinergic agonist ATP induced a rapid efflux of 45Ca2+ from cells loaded with 45Ca2+. Replacement of extracellular Na+ with choline+, significantly decreased the adenosine triphosphate-induced efflux of 45Ca2+. Furthermore, adenosine triphosphate-induced uptake of 45Ca2+ was increased when extracellular Na+ was replaced with choline+, compared with the uptake seen in Na+ buffer. Replacing extracellular Na+ with choline+, increased resting levels of cytosolic free Ca2+ from 50 +/- 2 nM (mean +/- SE) to 81 +/- 3 nM (P less than 0.05) in Fura 2 loaded cells. In cells preincubated with 1 mM ouabain for 30 min, resting cytosolic free Ca2+ increased to 73 +/- 3 nM (P less than 0.05). In a Na+ buffer, the adenosine triphosphate-induced transient increase in cytosolic free Ca2+ was 872 +/- 59 nM, compared with 1070 +/- 63 nM in choline+ buffer (P less than 0.05). The plateau level of cytosolic free Ca2+ in response to adenosine triphosphate was 130 +/- 16 nM in Na+ buffer, compared with 209 +/- 9 nM in choline+ buffer (P less than 0.05). Readdition of Na+ to the plateau phase decreased cytosolic free Ca2+ to 152 +/- 5 nM. Stimulating the cells with 10 microM of the Na(+)-selective monovalent ionophore monensin increased cytosolic free Ca2+ from 53 +/- 9 nM to 124 +/- 16 nM (P less than 0.05). This increase in cytosolic free Ca2+ was dependent on both extracellular Na+ and extracellular Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585818 TI - The polycationic compound gentamicin inhibits the calcium paradox in guinea-pig hearts. AB - The polycationic drug gentamicin and two calcium antagonists were studied with respect to their protecting action against the calcium paradox in perfused guinea pig hearts. Besides the mechanograms the release of creatine kinase was recorded; in parallel experiments the Na(+)-content of the hearts was measured before and at the end of the Ca(2+)-lack period, and during re-exposure to normal [Ca2+]0. The calcium paradox was induced by perfusion, for 50 s, with Ca(2+)-free solution containing EGTA (3 x 10(-4) M). Nifedipine and verapamil in concentrations which reduced the equilibrium contractile force by 50%, only mitigated the extent of the calcium paradox, whereas gentamicin applied in a concentration also reducing the contractile amplitude by 50% was able to suppress the calcium paradox completely. The dose-response curves for nifedipine, with respect to the reduction of contractile force and contracture, were identical. In contrast, gentamicin was more effective in attenuating the contracture of the paradox than in reducing the equilibrium contractile force. The large gain of Na+ during the Ca(2+)-lack period was diminished by both nifedipine and gentamicin. The partial protection of calcium antagonists can be related to their interference with the uptake of Na+ through L-type Ca(2+)-channels during the Ca(2+)-lack period, whereas gentamicin seems to act by an additional inhibition of the Na/Ca exchange during the re-exposure to normal [Ca2+]0. PMID- 1585819 TI - Plasma levels of oxytocin after food deprivation and hypoglycaemia, and effects of 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin on blood glucose in rats. AB - Oxytocin has been shown to influence insulin, glucagon and blood glucose levels in various experimental situations. The present study was performed in order to obtain support for a possible interaction of glucose and oxytocin under physiological conditions. We therefore studied whether or not short-term food deprivation (24 hours) affects basal oxytocin levels in male, female and lactating rats, since this is a situation when glucose is mobilized to prevent hypoglycaemia. Secondly, we studied whether oxytocin levels rise in a situation when blood glucose levels fall, i.e. following i.p. injection of insulin (20 U kg 1). In order to explore the role of oxytocin more directly, we investigated whether i.p. injection of the oxytocin antagonist 1-deamino-2-D-Tyr-(OEt)-4-Thr-8 Orn-oxytocin affects blood glucose levels. Plasma levels of oxytocin, insulin and glucagon were measured with radioimmunoassay in samples obtained after decapitation. We found that oxytocin levels were significantly increased following short-term food deprivation in lactating rats. We also found that insulin-induced hypoglycaemia could elevate plasma levels of oxytocin in female and male rats. In addition, administration of an oxytocin antagonist cause a small, but significant decrease in blood glucose levels after 30 min. These data imply that oxytocin may be one of several factors that take part in the control of blood glucose regulation. PMID- 1585820 TI - Functional and morphological comparisons between cochlear outer hair cells and muscle tissues in the guinea-pig. AB - The effect of polylysine on the motility of outer hair cells and various muscle types was compared. Poly-L-lysine and its stereoisomer, poly-D-lysine, inhibited acoustically induced length changes of isolated outer hair cells from the guinea pig hearing organ. The frequency specific displacements of the hearing organ in response to a tone stimulus are also inhibited to polylysine (Brundin et al. 1991). Poly-L-lysine, and its stereoisomer, irreversibly attenuated motile responses to transmural stimulation of guinea-pig ileum, vas deferens and taenia coli in a dose dependent manner, but were without significant effect on motile responses in skeletal and heart muscle. L-lysine, D-lysine, and the negatively charged polyaminoacid poly-L-aspartate, were without significant effect on outer hair cell and smooth muscle motility. The inhibitory effect of polylysine in smooth muscle is a direct effect on the muscle cell since polylysine attenuated acetylcholine- and adenosine triphosphate-induced contractions in the ileum, and ATP- or noradrenaline-induced contractions in the vas deferens. Pillar structures, believed to be of importance to excitation contraction coupling, were compared. In heart and skeletal muscle the pillars span the gap between sarcoplasmic reticulum and T-tubuli, deeply recessed into the muscle cell. In smooth muscle and outer hair cell the pillars are in closer relation to the cell exterior. The length of the pillars of the outer hair cells exceeds by two times that of smooth and skeletal muscle. The susceptibility of outer hair cells and smooth muscle tissue to the positively charged polylysine may indicate similarities in membrane or channel composition. PMID- 1585821 TI - The effect of immobilization on myotendinous junction: an ultrastructural, histochemical and immunohistochemical study. AB - The effect of immobilization on the myotendinous junction of the calf muscles in the rat was studied histochemically, immunohistochemically and morphometrically with a transmission electron microscope. After 3 weeks of immobilization, the contact area between the muscle cells and tendineal collagen fibres was reduced by almost 50% in both type I (slow-twitch) and type II (fast-twitch) muscle fibres. The terminal finger-like processes of the muscle cells became shallow and cylindrical or were completely atrophied. Their basal membranes were slightly thickened. Histochemically, the most remarkable alteration in the myotendinous junction was the marked decrease in the sulphate containing glycosaminoglycans. In the basal lamina of the muscle fibres, the glycosaminoglycan and proteoglycan content was also reduced. Immunohistochemical analyses revealed that the amount of type III collagen was markedly increased on the myotendinous interface, but the amount and distribution of type I collagen was not affected by immobilization. These findings suggest that immobilization causes degenerative changes at the myotendinous junction, which, in turn, most likely decrease its tensile strength and may predispose it to rupture during activity. PMID- 1585822 TI - Sprint training attenuates plasma ammonia accumulation following maximal exercise. PMID- 1585823 TI - L-NG-nitro arginine potentiates K(+)-induced contracture in the circular muscle of rabbit gastric corpus. PMID- 1585824 TI - Effect of a sulphonylurea on dog skeletal muscle performance during fatiguing work. PMID- 1585825 TI - The American Society for Bone and Mineral Research: normal or increased remodelling? PMID- 1585826 TI - The role of changes in mechanical usage set points in the pathogenesis of osteoporosis. AB - Mechanical usage (MU) effects on modeling drifts and BMU-based remodeling affect bone mass in defined ways. Decreased MU stops additions of bone by modeling and increases removal of bone next to marrow by remodeling. The latter effect thins cortices and reduces trabecular number, thickness, and connectivity. Return to normal MU makes remodeling begin conserving existing bone and leaves modeling still off. Hypervigorous MU can make modeling increase bone mass during growth and makes remodeling keep conserving it in children and adults. These effects can be said to begin when typical bone strains rise through two threshold ranges, one for remodeling and a higher one for modeling. Raising the thresholds while normal MU continues should give bone a spurious disuse message, whereupon disuse effects would begin. The bone anatomic and tissue dynamic patterns in acute and chronic disuse resemble those seen in developing and acquired postmenopausal osteoporosis and in other forms of osteoporosis, too. If some hormones, drugs, and other agents increase those thresholds, this could explain such similarities. PMID- 1585827 TI - The effect of ethnic group on appendicular bone mass in children. AB - The prevalence of senile and postmenopausal osteoporotic fractures is considerably higher in white than black women. Although the reasons for the genetic difference have not been elucidated, it has been suggested that ethnic differences in peak bone mass may be partially responsible. The present study examined appendicular bone mass (single-photon absorptiometry, SPA) in black and white children between the ages of 6 and 20 years. The sample was stratified for ethnic group, age, and sex. The effect of weight, height, puberty, and skinfold thickness on bone mass was also assessed. The bone width (BW) and bone mineral content (BMC) of males were significantly higher than those of females (p less than 0.0001). There were no statistically significant differences in bone mineral content normalized for bone width (BMC/BW) between the sexes (p = 0.1743 for whites and p = 0.5456 for blacks). The bone mass parameters of black girls were generally lower than those of white girls. After adjusting for height, BMC and BMC/BW of black girls tended to be greater than those of white girls (unadjusted p = 0.0258 for BMC and p = 0.0340 for BMC/BW). White boys tended to have greater bone mass parameters than black boys. After adjusting for height the trends disappeared. Thus, unlike the studies of bone mass in adults from the United States, we were unable to show that age-matched black children have higher bone mass than whites. After adjusting for height, however, the bone mass of black children (especially black girls) was marginally, but not significantly, greater than that of white girls. PMID- 1585828 TI - Inhibition of bone resorption in vitro by human enkephalinase (EC 3.4.24.11), a neutral metalloendopeptidase. AB - Bone metabolism is regulated by a wide variety of both circulating and locally produced peptides. The activity of such agents must be regulated, and one potential regulating mechanism is the inactivation of these peptides by locally produced proteolytic enzymes. One candidate for such a class of enzymes is enkephalinase (EC 2.3.24.11), a membrane-bound neutral metalloendopeptidase that inhibits the activity of a range of biologically active peptides, including interleukin-1 (IL-1), a potent bone-resorbing agent. In this study, we examined the effects of human enkephalinase on bone resorption in cultures of fetal rat long bones. We found that partially purified and highly purified enkephalinase inhibited bone resorption stimulated by parathyroid hormone (PTH) and IL-1 alpha. The effects on PTH-stimulated resorption were reversible, but enkephalinase did not inhibit prestimulated resorption. Enkephalinase also inhibited resorption induced by the nonpeptide stimulators 1,25-(OH)2D3, retinoic acid, and prostaglandin E2 (PGE2). In addition, preliminary studies confirmed a previous report of the presence of an enkephalinase-like activity in osteoblast-like osteosarcoma cells. These data are consistent with the hypothesis that proteolytic enzymes, such as enkephalinase, may play a role in the local regulation of bone resorption. PMID- 1585829 TI - Physicochemical action of potassium-magnesium citrate in nephrolithiasis. AB - Effect of potassium-magnesium citrate on urinary biochemistry and crystallization of stone-forming salts was compared with that of potassium citrate at same dose of potassium in five normal subjects and five patients with calcium nephrolithiasis. Compared to the placebo phase, urinary pH rose significantly from 6.06 +/- 0.27 to 6.48 +/- 0.36 (mean +/- SD, p less than 0.0167) during treatment with potassium citrate (50 mEq/day for 7 days) and to 6.68 +/- 0.31 during therapy with potassium-magnesium citrate (containing 49 mEq K, 24.5 mEq Mg, and 73.5 mEq citrate per day). Urinary pH was significantly higher during potassium-magnesium citrate than during potassium citrate therapy. Thus, the amount of undissociated uric acid declined from 118 +/- 61 mg/day during the placebo phase to 68 +/- 54 mg/day during potassium citrate treatment and, more prominently, to 41 +/- 46 mg/day during potassium-magnesium citrate therapy. Urinary magnesium rose significantly from 102 +/- 25 to 146 +/- 37 mg/day during potassium-magnesium citrate therapy but not during potassium citrate therapy. Urinary citrate rose more prominently during potassium-magnesium citrate therapy (to 1027 +/- 478 mg/day from 638 +/- 252 mg/day) than during potassium citrate treatment (to 932 +/- 297 mg/day). Consequently, urinary saturation (activity product) of calcium oxalate declined significantly (from 1.49 x 10(-8) to 1.03 x 10(-8) M2) during potassium-magnesium citrate therapy and marginally (to 1.14 x 10(-8) M2) during potassium citrate therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585830 TI - Developmental changes in calcium kinetics in children assessed using stable isotopes. AB - Total exchangeable calcium pool size (TEP) and bone calcium accretion rate (Vo+) were measured using stable isotopes in healthy children and young adults. 42Ca or 46Ca was given intravenously to 10 children aged 10 months to 14 years and 3 women aged 23-33 years. Calcium kinetic parameters were determined using a two- or three-exponential curve of the resultant serum and urine tracer excesses. These data were compared with previously reported (radiotracer) kinetic studies of 21 children and 5 adults without known bone disease. Current results are comparable to those previously obtained, and the data from all studies were analyzed together. Total Vo+ was significantly greater in children aged 3-16 years than in adults (2.8 +/- 1.6 versus 0.7 +/- 0.2 g/day, p less than 0.01). Both TEP and Vo+ were significantly correlated to age independently of variations in body weight (p less than 0.01 for each). The ratio ko+ = Vo+/TEP was greater in children than adults (0.36 +/- 0.15 versus 0.12 +/- 0.03 day-1, p less than 0.001). These data demonstrate increased bone flow of calcium associated with increases in exchangeable calcium pools in children compared to adults. Vo+ and TEP may be maximum in early adolescence, associated with peak rates of net calcium accretion. The use of stable isotopes permits the safe evaluation of calcium kinetics in patients of all ages. PMID- 1585831 TI - Parathyroid hormone sensitizes long bones to the stimulation of bone resorption by 1,25-dihydroxyvitamin D3. AB - In response to hypocalcemia the serum PTH level increases rapidly followed by a PTH-induced rise in 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] production. Therefore, bone is first exposed to increased PTH levels before increased 1,25 (OH)2D3 levels. In the present study the effect of pretreatment with PTH on 1,25 (OH)2D3-induced bone resorption was examined. Bone resorption was measured as release of prelabeled 45Ca during culture from 17-day-old fetal mice radii/ulnae and metatarsals. Radii/ulnae and metatarsals are characterized by differences in development. In radii/ulnae mature osteoclasts are present, whereas in metatarsals only different stages of preosteoclasts can be found. Preincubation for 24 h but not 4 h with PTH increases the stimulation of bone resorption by 1,25-(OH)2D3 in fetal radii/ulnae but not in metatarsals. Coincubation of PTH and 1,25-(OH)2D3 did not result in a significant change in bone resorption compared to 1,25-(OH)2D3 alone. The observed difference in the effect of pretreatment with PTH between radii/ulnae and metatarsals indicates that PTH does not stimulate the development of early osteoclast precursors but that a certain level of differentiation of the osteoclast precursor is required. Pretreatment with prostaglandin E2 resulted in an effect similar to that of PTH. Inhibition of prostaglandin synthesis by indomethacin prevented the potentiation of 1,25 (OH)2D3-induced bone resorption by pretreatment with PTH. Thus, the present study demonstrates that PTH sensitizes responses to 1,25-(OH)2D3. PTH must be present before 1,25-(OH)2D3 to observe a potentiation of 1,25-(OH)2D3-induced bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585832 TI - Sequential and precise in vivo measurement of bone mineral density in rats using dual-energy x-ray absorptiometry. AB - In the design of new strategies for the treatment of osteoporosis, noninvasive, precise, and sensitive bone mass measurement capable of detecting changes over short periods of time in small animals is essential. Most of the models described thus far require the sacrifice of the animals and/or display low reproducibility. Using a dual-energy x-ray absorptiometer (DEXA; Hologic QDR-1000) in an ultrahigh resolution mode, we measured bone mineral density (BMD) in rats at the levels of lumbar spine (L1-4), proximal tail (caudal vertebrae C2-4), and tibia. Accuracy was evaluated by measuring the mineral content of bone powder capsules (within the range of rat vertebrae BMD), under 0.5-3 cm water to mimic variations in soft tissue thickness. The bone powder capsule mineral content was highly correlated with chemically determined hydroxyapatite content (r = 0.999). In vivo reproducibility was evaluated by calculating the coefficient of variation (CV = 100 x SD/mean) of four to six BMD measurements, each time with repositioning, in seven rats (220-500 g body weight). CV was 1.36 +/- 0.32% (x +/- SD) for lumbar spine, 0.66 +/- 0.50% for proximal tail, and 1.12 +/- 0.45% for tibia. The ability to detect BMD changes was investigated by measuring BMD before and every 4 weeks after ovariectomy (OVX) in 270 g rats, pair fed during the whole experiment. Compared with sham-operated control animals, a highly significant difference in lumbar spine BMD was observed 4 weeks after OVX, which reached a maximum by 8 weeks and remained stable thereafter. At the level of the proximal tibia, the difference was maximal 4 weeks after OVX.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585833 TI - Crush fracture syndrome in senile osteoporosis: a nutritional consequence? AB - Osteoporosis is a very important age-related health problem. The body's composition changes with age, and these changes are a true reflection of aging and of the individuals's nutritional status. Mineral content changes have been reported in vertebral osteoporosis. Interestingly, enough, there have not been reports on concomitant water, fat, and fat-free mass changes associated with this condition. In this report, changes in the latter parameters are compared between patients with osteoporosis and controls. The four components (water, mineral, fat, and fat-free mass) were found significantly reduced (p less than 0.001) in osteoporosis. Serum albumin and protein mass were also reduced (p less than 0.001). PMID- 1585834 TI - An assay system utilizing devitalized bone for assessment of differentiation of osteoclast progenitors. AB - The present study provides a novel assay system to examine the differentiation of osteoclast progenitors on devitalized bone slices. We used the population of bone cells liberated enzymatically from 14-day-old mouse embryonal calvariae as a source of osteoclast progenitors. The analysis of differentiation of osteoclast progenitors into preosteoclasts and mature osteoclasts was assessed in terms of the formation of TRAP-positive cells and pits or resorption lacunae, respectively, on devitalized bone slices. Osteoclasts having bone-resorbing activity appeared when the calvarial cell population was cultured in the presence of 1 alpha,25-(OH)2D3 on devitalized bone slices. The resorbing activity increased in a 1 alpha,25-(OH)2D3 dose-related manner. However, calcitonin, a potent inhibitor of differentiation and activation of osteoclast lineage cells, reduced the area of the resorption lacunae in a dose-dependent fashion. The bone resorbing cells on the bone slices expressed an obvious ruffled border and clear zone, structures specific to mature osteoclasts. These results suggest that osteoclast progenitors in the mouse calvarial population examined differentiated into mature osteoclasts in the presence of 1 alpha,25-(OH)2D3 on devitalized bone slices. Further, using this assay system we assessed the effect of some other osteotropic factors on the differentiation of osteoclast progenitors to mature osteoclasts. IL-1, IL-6, and PTH increased the formation of TRAP-positive cells and pits and the area of resorption lacunae in a dose-dependent fashion. However, prostaglandin E2 was unable to induce the formation of resorption lacunae, although a significant appearance of TRAP-positive cells was observed at a concentration of 200 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585835 TI - Mineral crystals in calcified tissues: a comparative study by SAXS. AB - The shape, the typical orientation, and the average size of mineral crystals in different types of mineralized tissues were investigated by means of small-angle x-ray scattering (SAXS). To rule out eventual artifacts due to sample preparation, four different standard preparation techniques were used and a comparison showed that the SAXS results were identical for all four methods. In mineralized turkey leg tendon, a frequently used model system for bone, the crystals were found to be typically plate-like with a thickness of the order of 2 nm. This stands in contrast to the case of bone (calvaria, femur, and iliac crest) from mouse, rat, and dog, where mainly needle-like crystals were found. The thickness of these crystals ranged from 3 to 4 nm but was remarkably constant for different bones of a given animal. The preferred orientation of the needle like crystals was along the main axis of the femur and within the surface of the calvaria (for mouse, rat, and dog). The mineral plates in turkey leg tendon were located inside the hole zone and oriented along the fibril axis. Finally, no periodic arrangement of the crystals inside the hole zone of the collagen could be found. PMID- 1585836 TI - Rat osteoclasts adhere to a wide range of RGD (Arg-Gly-Asp) peptide-containing proteins, including the bone sialoproteins and fibronectin, via a beta 3 integrin. AB - The ligand binding ability of rat osteoclast adhesion receptors was investigated in an attachment assay using osteoclasts disaggregated from bone. Osteoclasts adhered well to the Arg-Gly-Asp (RGD)-containing proteins osteopontin (bone sialoprotein I) and BSP (bone sialoprotein II), vitronectin, fibrinogen, von Willebrand factor, and fibronectin. Osteoclasts also adhered, but less strongly, to type I collagen. No attachment of osteoclasts was observed to thrombospondin, tenascin, laminin, or a range of non-RGD-containing bone proteins and proteins from other sources. The attachment of osteoclasts to all ligands was abolished in the presence of GRGDSP peptide, indicating the involvement of the RGD cell binding sequence in ligand binding. Attachment of osteoclasts to all substrates, with the exception of type I collagen, was also strongly inhibited by the addition of monoclonal antibody F11 to the beta 3 integrin subunit, indicating that a beta 3 integrin, probably the vitronectin receptor, was involved. Attachment to type I collagen was blocked by EDTA chelation of divalent cations and was not significantly affected by anti-beta 3 or anti-beta 1 antibodies; when taken with the inhibition by RGD peptide, this suggests the involvement of various receptors, possibly including nonintegrin collagen receptors, in the binding of osteoclasts to this protein. These results define the wide range of ligands for extracellular matrix receptors in osteoclasts in vitro. It remains to be established which of these proteins are important in osteoclast adhesion and osteoclastic bone resorption in vivo. PMID- 1585837 TI - Integrins on rat osteoclasts: characterization of two monoclonal antibodies (F4 and F11) to rat beta 3. AB - Two monoclonal antibodies, F4 and F11, were raised to newborn rat bone cell suspensions. These antibodies are shown by immunocytochemistry on tissue sections to recognize an antigen shared between osteoclasts, megakaryocytes, and platelets. Immunoprecipitation analysis of the antigen from C6 rat glial cells followed by SDS-PAGE showed a heterodimeric molecule with a characteristic integrin-like shift in apparent molecular mass upon reduction (137/78 kD nonreduced; 118/100 kD reduced); the low-molecular-mass band comigrates with the beta 3 subunit precipitated with polyclonal antihuman vitronectin receptor antiserum, and the high-molecular-mass band comigrates with the alpha v subunit precipitated with a polyclonal antiserum to a C-terminal amino acid sequence of human alpha v. Antibody F4 strongly cross-reacts with human cells and is shown in cross-blocking experiments and immunoprecipitation analysis with a human melanoma cell line DX3 to recognize a seemingly identical molecule as identified by anti alpha v beta 3 monoclonal antibody 23C6. Expression of F4 and F11 is reduced in platelets from a patient heterozygous for Glanzmann's thrombasthenia. Taken together, these results indicate that F4 and F11 recognize rat CD61, the integrin beta 3 chain, which, as was confirmed with polyclonal anti CD61 antisera, is highly expressed in rat osteoclasts. These antibodies may be useful tools in investigating the biochemical nature and biologic function of beta 3 integrins in rat osteoclasts. Additionally, because high expression of beta 3 in vivo is restricted to osteoclasts, megakaryocytes, and platelets, these antibodies may be used to help identify osteoclasts in tissue sections and bone cell suspensions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585838 TI - Derivation of osteoclasts from hematopoietic colony-forming cells in culture. AB - The osteoclast is known to be derived from the hematopoietic stem cell, but its lineage remains controversial. There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hematopoietic precursors. To analyze osteoclastic lineage, colonies were generated in semisolid medium from mouse spleen cells in the presence of Wehi-conditioned medium, interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), or macrophage colony-stimulating factor (M-CSF) with or without erythropoietin (epo). After 5-8 days colonies were picked and phenotyped and incubated with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] on bone slices or coverslips with bone marrow-derived cell lines (ts8 or ST2) that induce osteoclastic differentiation. Cells of osteoclastic phenotype [as judged by calcitonin receptor (CTR) expression or bone resorption] were observed only in multilineage colonies. The ability of cells that generate macrophage colonies (CFU-M) to generate osteoclasts was tested by incubating alveolar or peritoneal macrophages on ts8 or ST2 cells. Despite colony formation, no osteoclastic differentiation was detectable. Last, individual cells from blast cell colonies were incubated (1 cell per culture well) on ts8 or ST2 cells in the presence of 1,25-(OH)2D3 and epo (to expose the lineage potential of the plated cell). We found CTR-positive (CTRP) cells in 6 of 66 macrophage colonies, 7 of 12 granulocyte-macrophage (GM) colonies, and 49 of 50 colonies containing multiple lineages other than GM colonies. No single-lineage CTRP colonies were observed. Although most macrophage colonies did not contain CTRP, no CTRP were observed in colonies from which macrophages were absent. These results suggest that osteoclasts are derived from a multilineage precursor rather than from CFU-M. PMID- 1585839 TI - Substance use among Hispanic and non-Hispanic adolescents. AB - This study compared lifetime prevalence data on substance use with demographic and psychosocial variables among 2,821 Hispanic and non-Hispanic white students from two Southwestern cities. Study findings revealed that ethnic-racial background factors were not the strongest predictors of substance use. Rather, when the analyses accounted for school grades and for maternal education, non Hispanic youth had higher lifetime substance use rates than Hispanic youth. Study findings suggest that preventive intervention and treatment efforts for substance abuse problems among adolescents should consider sociodemographic risk factors as well as ethnic-racial factors. PMID- 1585840 TI - The body image detection device versus subjective measures of weight dissatisfaction: a validity comparison. AB - Several procedures have been developed to measure body image distortion. A recently developed device is the Body Image Detection Device (BIDD), which includes a measure of perceptual size distortion (BPI) and subjective ratings of relative weight (SRI). Initial studies have supported the validity and reliability of the BIDD BPI and SRI in mainly bulimic patients, though studies which question the validity of the BIDD (especially the BPI) have appeared. One purpose of the present study was to examine the BIDD's validity in anorectic as well as bulimic patients and to compare both to a psychiatric control group. A second purpose of the study was to compare the validity of the BIDD to alternative measures. Thus, this study also compared the BIDD indices with simple measures of body weight dissatisfaction. The results did not support the validity of the BIDD BPI as a measure of body image disturbance, moderately supported the SRI, and did support the measures of weight dissatisfaction. PMID- 1585841 TI - An assessment of nicotine gum as an adjunct to freedom from smoking cessation clinics. AB - The Freedom from Smoking clinic programs offered by the American Lung Association are in widespread use. These programs were developed in the 1970s prior to the availability of nicotine gum in the United States. It was hypothesized that the addition of nicotine gum to these clinics (thereby including both behavioral and pharmacologic intervention) would boost abstinence outcome significantly. Two hundred and seventy-three persons were randomly assigned to Freedom from Smoking clinics with or without prescription of nicotine gum. Abstinence outcomes at one week favored the nicotine gum conditions (86.3% of nicotine gum subjects were abstinent as opposed to 70.9% of comparison subjects, chi 2(1) = 9.79, p = .002). Effects for gum were no longer significant at later follow-ups, however, Overall duration and level of nicotine gum use were considerably less than optimal. In the absence of a placebo gum control group, expectancy cannot be eliminated as a possible explanation of the short-term results. PMID- 1585842 TI - The effects of a restricted feeding regimen on cigarette smoking in humans. AB - The effects of 3 days of restricted feeding (800 kcal/day) on cigarette consumption, smoke exposure, and mood were studied in five male research volunteers. A within-subjects design was used in which subjects were exposed in an inpatient research unit to either a nutritionally-balanced diet containing 800 kcal (RESTRICTED DIET) or 3,000 kcal (NORMAL DIET) per day for 3 consecutive days. At least 2 weeks separated diet conditions. Dependent measures included number of cigarettes smoked per day in each diet condition, biological exposure levels (carbon monoxide and plasma cotinine levels), and mood. Number of cigarettes smoked per day did not differ significantly across diet conditions. Biological exposure to carbon monoxide and to cotinine, a metabolite of nicotine indicative of chronic nicotine exposure, also did not differ significantly between conditions. Fatigue scores from the Profile of Mood States were significantly elevated in the RESTRICTED DIET condition. Not surprisingly, subjects in this condition also reported feeling more hungry throughout the day than in the NORMAL DIET condition. From our study results, we conclude that a short period of "dieting," and the resulting hunger elicited from such a diet, do not increase cigarette consumption or smoke exposure in humans. PMID- 1585843 TI - Alcohol expectancies, social and environmental cues as determinants of drinking and perceived reinforcement. AB - Increasing evidence suggests that outcome expectancies and environmental cues interact to influence post-drinking behaviors. Using an experimental methodology in a simulated social drinking setting, this research tested the potential influence of expectations for the effects of drinking, environmental cues, and beverage content on ad lib consumption and post-drinking self-perception. Eighty eight moderate to heavy-drinking males were randomly assigned to one of eight experimental conditions in which beverage content (alcohol or placebo), social environment (friendly or unfriendly), and physical environment (simulated bar or residence) were varied. Subjects were further divided into high and low groups on three outcome expectancy factors. Unaffected by environmental cues, beverage self administration increased when subjects strongly expected behavioral impairment from drinking but received placebo beverage. Post-drinking reports of disinhibition increased in response to friendly social cues but were not affected by beverage content or amount. Results therefore suggest that individual's beliefs about the effects of drinking influence the amounts of beverage they consume, whereas social cues more greatly affect post-drinking self-perception. PMID- 1585844 TI - Reliability of self-reported alcohol consumption before and after December. AB - The purpose of this study is to assess the reliability of a self-reported 12 month alcohol measure obtained 1 month before and after December. As part of a larger study involving multiple telephone contacts, this sample consisted of 112 volunteers who drank alcohol at least monthly. During telephone interviews, respondents were asked about their drinking in the last 12 months in November, 1989, and again in January, 1990. The results indicate that the sample reported significantly lower alcohol use during the past year after December. These lower estimates occurred in both the frequency and the average quantity per occasion measures. There were significant reductions in reports of alcohol consumption in the last 12 months after December for the group which was contacted more often (greater than or equal to 7 times during December). The group contacted fewer times (less than or equal to 2 times during December) also reported lower, but not significant, amounts of alcohol consumed after December. These findings indicate that the prevailing idea that reports of last year's typical drinking obtained in January will be overstated because of the holiday season may be unfounded. PMID- 1585845 TI - Thermogenic effects of pre-prandial and post-prandial exercise in obese females. AB - The thermogenic effects of pre- and postprandial exercise was examined in six obese premenopausal females. Using open circuit calorimetry, energy expenditure was measured for 3 hours following five separate treatments: Resting Control, Exercise Only (25 min cycle at 60% VO2 max), Meal Only (902 kcal mixed meal), Exercise-Meal, and Meal-Exercise. Meal Only, Exercise-Meal, and Meal-Exercise were significantly higher than Rest Only and Exercise Only treatments. However, Meal-Exercise resulted in the greatest energy expenditure. These results suggest that in obese female subjects exercise following a meal will produce the greatest thermogenic response and could possibly influence weight maintenance or weight loss if implemented in food and exercise patterns of behavior. PMID- 1585846 TI - Correlates and predictors of smoking among black adolescents. AB - Little is known about the etiology of cigarette smoking among minority populations. This study examines the correlates and predictors of smoking among inner-city black seventh graders (N = 608). Enhanced self-reports of cigarette smoking were collected along with data concerning demographic, social, and psychological factors hypothesized to promote smoking initiation. Results indicate that social environmental factors, such as the smoking status of friends and siblings, and individual factors, such as refusal assertiveness, general assertiveness, and age are predictive of current smoking. Similarly, the smoking status of friends, attitudes concerning the harmful effects of smoking, and low self-esteem concerning schools are predictive of behavioral intention to smoke in the future. Overall, the factors that were the most salient predictors of smoking for the black adolescents in this study are generally congruent with the existing literature for other populations. PMID- 1585847 TI - Clinical significances of superoxide dismutases: changes in aging, diabetes, ischemia, and cancer. PMID- 1585848 TI - Renal biochemistry and physiology: pathophysiology and analytical perspectives. PMID- 1585849 TI - The polymerase chain reaction: clinical applications. PMID- 1585850 TI - Oncogenes in cancer. PMID- 1585851 TI - Gastrin and cancer. PMID- 1585852 TI - A biochemical approach to renal stone formation. PMID- 1585853 TI - Biochemistry of the uremic syndrome. PMID- 1585854 TI - Predictive value of apolipoproteins in a prospective survey of coronary artery disease in men. AB - Some studies have suggested that measurements of apolipoproteins may be valuable in the clinical assessment of susceptibility to coronary artery disease, over and above the lipoprotein lipids. Only a few of these studies have been prospective in nature and further knowledge is therefore needed to clarify the issue. The independent prognostic value of apolipoproteins (apo-B, apo-AI and apo[a]) with regard to coronary artery disease was estimated from a prospective survey among 1,332 randomly selected Icelandic men, aged 45 to 72 years, participating in a health survey from 1979 to 1981. The group was followed for 8.6 years, and during that period 104 men had fatal or nonfatal myocardial infarction. The Cox's proportional hazards model was used to estimate the significance of independent variables. The results of multivariate analysis showed that apo(a) was a significant independent risk factor (odds ratio 1.22 for 1 SD), but apo-AI was a stronger negative risk factor (odds ratio 0.70 for 1 SD). Apo-B was a highly significant risk factor in a univariate analysis, but not in a multivariate analysis when serum cholesterol was included. Previous population surveys in Iceland have confirmed the importance of cigarette smoking, cholesterol, triglycerides and blood pressure as risk factors for coronary artery disease. The present results illustrate additional importance of apo-AI and apo(a) concentrations in predicting coronary artery disease among Icelandic men, whereas apo-B did not contribute anything further to the prediction than serum total cholesterol. PMID- 1585855 TI - Increased IgM-anticardiolipin antibodies in patients with restenosis after percutaneous transluminal coronary angioplasty. AB - Increased anticardiolipin antibodies (acL) are often associated with arterial thrombosis in patients with autoimmune diseases. A mural thrombus at the site of percutaneous transluminal coronary angioplasty (PTCA) has been suggested as the initial cause for restenosis after primarily successful PTCA. In this study, IgM- and IgG-acL were determined in 65 men with coronary artery disease treated by PTCA; patients with infectious and autoimmune diseases were excluded from the study. Follow-up coronary angiography was performed 12 months after PTCA; restenosis was defined as greater than or equal to 50% reduction in diameter of the coronary vessel. The series comprised 2 groups: 34 patients (mean age 56 +/- 8 years) with (group A) and 31 (mean age 55 +/- 9 years) without (group B) restenosis. Medical history and laboratory findings were comparable in both groups. In patients with restenosis, IgM-acL were more often increased (9 of 34) than were those in patients without restenosis (2 of 31; p less than 0.05); IgG acL values did not differ in both groups. Furthermore, there was no correlation between any vascular risk factors or laboratory findings, or both, with both IgM- and IgG-acL levels. Thus, IgM-acL appear to be independent indicators for an increased risk for restenosis after PTCA. Our observations suggest that an autoimmune mechanism may have a role in restenosis. PMID- 1585856 TI - Safety and clinical use of exercise testing one to three days after percutaneous transluminal coronary angioplasty. AB - To evaluate both the safety and clinical use of predischarge symptom-limited exercise testing after successful uncomplicated percutaneous transluminal coronary angioplasty (PTCA), 100 patients were randomized to undergo exercise testing (n = 50) or no exercise testing (n = 50). There were no differences in clinical or angiographic characteristics between the groups. Exercise testing was performed 38 +/- 14 hours after PTCA. Patients who exercised achieved 71 +/- 12% of predicted maximal heart rate, with 38% reaching greater than or equal to stage III of the Bruce protocol. No patient in either group developed cardiac complications during 48-hour follow-up. Of the 11 patients with a positive test result, 92% had angiographically incomplete revascularization. Attending physicians (n = 16) were questioned both before and after exercise testing about when, after discharge, they would allow their patient to perform each of 11 specific activities of daily living. Questionnaires were administered to physicians at similar time frames for patients in the no-exercise group. Comparison of the responses between initial and repeat questionnaires showed that patients in the exercise group (with a test result negative for ischemia) were allowed to perform 7 of 11 activities, including return to work, earlier (p less than 0.05) than the no-exercise patients. These data indicate that in this well defined group of patients, symptom-limited exercise testing early after PTCA appears to be safe, and alters physician management in allowing patients with a negative test result to return to various activities at an earlier date. Such testing may be useful in counseling patients after PTCA. PMID- 1585857 TI - Transthoracic high-frequency two-dimensional echocardiography, Doppler and color flow mapping to determine anatomy and blood flow patterns in the distal left anterior descending coronary artery. AB - Combined high-frequency transthoracic ultrasound, pulsed Doppler and color flow mapping were used to image and assess blood flow velocity in the distal left anterior descending artery (LAD) in 56 consecutive patients. All patients subsequently underwent coronary angiography. The LAD was imaged in 19 patients (34%), and the diameter was measured in 12 with high-quality images (mean diameter 1.8 mm +/- 0.08). In 1 patient, the penetrating branches of the LAD were imaged. The distal LAD appeared normal by ultrasound in 18 patients, and a significant stenosis was detected in 1; angiography confirmed the ultrasound findings. There were no false negative results. Characteristic biphasic flow with higher velocities in diastole were noted in all 19 patients. Color flow mapping demonstrated normal laminar flow, except in the patient with a distal stenosis. Pulsed Doppler confirmed an increased velocity distal to the stenosis in this patient. This study is the first transthoracic evaluation of the hemodynamic effects of a coronary artery stenosis, and the first in vivo description of blood flow disturbance at a distal coronary stenosis in humans. The clinical use of this technique is limited, because only the distal portion of the LAD is visualized. However, it may provide a noninvasive means of assessing distal LAD diameter and blood flow, and changes in these parameters under a variety of physiologic, pharmacologic and interventional stimuli. PMID- 1585858 TI - Accuracy of dobutamine stress echocardiography in detecting coronary artery disease. AB - The diagnostic accuracy of dobutamine stress echocardiography (DSE) (incremental infused doses of 5, 10, 20 and 30 micrograms/kg/min) was evaluated in 141 patients who underwent coronary arteriography within 2 weeks of DSE. All patients were being evaluated for known or suspected coronary artery disease (CAD). DSE was interpreted blindly as normal or showing evidence of CAD, depending on the presence of resting or inducible wall motion abnormalities. Coronary arteriograms were reviewed in a blinded, quantitative fashion. DSE had a sensitivity of 96% for detecting patients with CAD, and a specificity of 66%. For the 53 patients with normal resting wall motion, sensitivity was 87% and specificity 91%. The protocol was well-tolerated by all patients. In comparison with wall motion analysis, 12-lead electrocardiograms during dobutamine infusion revealed ischemic changes in only 17% of patients with CAD. It is concluded that DSE is a clinically useful and accurate means for detecting CAD, its specificity is hindered in patients with resting wall motion abnormalities, and it can safely be used in patients with known cardiac disease. PMID- 1585859 TI - Comparison of the clinical profile and outcome of women and men in cardiac rehabilitation. AB - Few data are available regarding the outcome of women in cardiac rehabilitation. To determine whether women differ from men in clinical profile and outcome, 225 consecutive patients were prospectively evaluated in an urban, multidisciplinary, exercise-based cardiac rehabilitation program. Among the 51 women (age 56 +/- 10) and 174 men (age 54 +/- 10), most were: white (84%), married (64%), employed (63%), had had myocardial infarction or revascularization, or both (66%), and traveled less than 10 miles to the program (92%). Risk profiles revealed obesity in 48% (mean Metropolitan Relative Weight = 124 +/- 22%), hypertension in 47%, smoking in 23%, diabetes in 16%, and mean cholesterol of 236 +/- 45 mg/dl. Compared with men, more women were nonwhite, unemployed, unmarried, hypertensive or diabetic (p less than 0.0001) and had higher cholesterol (p less than 0.01). Compliance rates were similar for women (51%) and men (63%) (p = not significant). Univariate predictors of program noncompliance differed between women and men. Initial exercise capacity was less for women than for men, but both groups achieved a similar training effect. Women increased their exercise time by 31% and peak METs by 30%, whereas men showed a 21% increase in exercise time and 16% increase in peak METs achieved (p less than 0.001). Thus, in this cardiac rehabilitation program, women have a less favorable risk factor profile and differ from men with regard to baseline demographics and predictors of program completion. Women, however, have similar rates of compliance and achieve the same improvement in functional capacity with training. PMID- 1585860 TI - Usefulness of dipyridamole-thallium scanning for preoperative evaluation of cardiac risk for nonvascular surgery. AB - The ability to stratify cardiac risk before nonvascular surgery using clinical markers and dipyridamole-thallium scanning (DTS) was assessed for patients with known or suspected coronary artery disease unable to exercise. Of 100 consecutively studied patients who proceeded to nonvascular surgery, 9 (9%) experienced greater than or equal to 1 perioperative cardiac ischemic event, including death in 2 patients (2%) and nonfatal myocardial infarction in 2 (2%). Logistic regression identified 2 clinical predictors (age greater than 70 years and history of heart failure), and 1 DTS (thallium redistribution) predictor of events. Of 45 patients with neither clinical variable, none (0%; 95% confidence intervals [CI] 0 to 8%) had events. Of 55 patients with greater than or equal to 1 clinical marker, 9 (16.4%; 95% CI 7 to 26%) had events. Within this subgroup, 1 of 31 patients (3.2%; 95% CI 0 to 16%) without thallium redistribution had events compared with 8 of 24 (33.3%; 95% CI 14 to 52%) with redistribution. An algorithm combining 5 independent clinical and 2 DTS predictors, derived previously in vascular surgery patients, was validated in the 100 nonvascular surgery patients. It is concluded that preoperative planar DTS is most useful to stratify selected nonvascular surgery patients at intermediate or high risk by clinical assessment. However, for almost half of those patients with known or suspected coronary artery disease, DTS may be unnecessary because of sufficiently low predictive value based on simple clinical descriptors. PMID- 1585861 TI - Quantitative angiographic and statistical methods to assess serial changes in coronary luminal diameter and implications for atherosclerosis regression trials. AB - The purpose of this study was (1) to determine a threshold for categorizing individual coronary lesions as either significantly progressing or regressing, (2) to determine whether multiple lesions within individual patients progress at independent rates, and (3) to calculate sample sizes for atherosclerosis regression trials. Seventeen patients with 46 significant lesions (2.7 lesions/patient) underwent repeat coronary arteriography 3.0 years apart. With use of the standard error of the mean change in diameter from initial to repeat catheterization across 5 pairs of consecutive end-diastolic frames, individual lesions were categorized as either significantly (p less than 0.01) progressing or regressing if there was a 0.27 mm change in minimum diameter or a 7.8 percent point change in percent stenosis. The mean diameter change of a sample of lesions can also be analyzed as a continuous variable using either the lesions or the patient as the primary unit of analysis. A lesion-specific analysis can be accomplished using a multiple regression model that accounts for the intraclass correlation (rho) in the degree of change among multiple lesions within individual patients. The intraclass correlations in percent stenosis (rho = 0.01) and minimum diameter (rho = -0.24) were low, indicating that disease progression in different lesions within individual patients is nearly independent. With use of this model, 50 patients per treatment group would permit the detection of a 5.5% difference between treatment group means in the change in minimum diameter and a 2.7% percentage point (not percent) difference in the change in percent stenosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585862 TI - Characterization of acute myocardial infarction by magnetic resonance imaging. AB - The T2-weighted spin-echo technique is currently the most frequently used magnetic resonance imaging (MRI) method to visualize acute myocardial infarction. However, image quality is often degraded by ghost artifacts from blood flow, and respiratory and cardiac contractile motion. To enhance the usefulness of this technique for detailed characterization of infarction, a velocity-compensated spin-echo pulse sequence was tested by imaging a flow phantom, 6 normal subjects and 17 patients with acute myocardial infarction. After preliminary studies were performed in 7 patients to determine optimal imaging parameters, a standardized imaging protocol was used in the next 10. The location of myocardial infarction identified by the electrocardiogram and coronary anatomy was correctly identified in 10 of 10 patients. Distribution of the injury within the left ventricle was clearly visualized, and showed that patients often had a mixture of transmural and nontransmural injury. Heterogenous distribution of signal intensity within the infarction suggested the presence of hemorrhage. Papillary muscle involvement was readily apparent. Signal intensity of the infarction (brightest segment) was increased by 89 +/- 31% compared with the mean of the remote segments. The myocardial/skeletal muscle ratio was significantly (p less than 0.001) increased for the infarction segments compared with that for remote myocardium, allowing quantitative analysis of segmental signal intensity. The MRI wall motion study obtained as part of this protocol demonstrated wall thickening in 58% of the infarction segments and in 6 of 10 patients. This finding suggested the presence of reversibly injured myocardium. In conclusion, the results demonstrate the potential of MRI for detailed tissue characterization after acute myocardial infarction. PMID- 1585863 TI - Reproducibility of electrophysiologic testing during antiarrhythmic therapy for ventricular arrhythmias secondary to coronary artery disease. AB - Although electrophysiologic studies are often used to assess antiarrhythmic drug efficacy in patients with ventricular tachycardia (VT), the reproducibility of these studies during therapy has not been definitively established. Confirmation studies were performed during drug therapy in 64 patients (51 men, mean age 63 years) with sustained ventricular arrhythmias induced during initial study to assess the reproducibility of drug effect. All patients had coronary artery disease. The stimulation protocol used included the serial introduction of up to 3 premature ventricular stimuli during sinus rhythm and with ventricular pacing at 2 pacing rates. Rapid ventricular pacing techniques were also used. Antiarrhythmic drug efficacy was confirmed in 77% of patients. Sustained VT was induced at repeat electrophysiologic study in 19% of patients during antiarrhythmic therapy that was previously thought to be effective. In summary, electrophysiologic study results during antiarrhythmic therapy exhibit significant day-to-day variability. Sustained VT can be induced during antiarrhythmic therapy that was previously defined as effective by programmed stimulation in a substantial number of patients. PMID- 1585864 TI - Reproducibility of isoproterenol tilt-table tests in patients with syncope. AB - To assess the reproducibility of head-up tilt-table testing 46 patients each underwent 2 isoproterenol tilt-table tests 1 to 6 weeks apart. Of 20 patients with an initially asymptomatic negative test result, 17 (85%) had a second negative test result. Of 20 patients whose initial test ended in syncope, 18 had a second test ending in syncope (n = 12) or presyncope (n = 6). Five of 6 patients whose first test ended in presyncope had a second test that ended in presyncope, and 1 had a second test that was asymptomatic. Finally, a total of 14 patients had at least 1 test (either the first or second) ending in presyncope, and 11 of these (79%) had another test ending in presyncope or syncope. The dose dependence of isoproterenol was irreproducible. The reproducibility of the duration of head-up tilt necessary to elicit symptoms of presyncope or syncope was determined in the 23 patients who had these symptoms on both tests. Symptoms developed monoexponentially with duration of head-up tilt with half-times of 1.4 to 2.6 minutes, but these times did not correlate significantly between tests. In a selected subgroup of 12 patients who developed syncope in the first test and either presyncope or syncope in the second test during administration of isoproterenol (5 micrograms/min), the time of onset of presyncope correlated well (r = 0.73, p = 0.007) as did that of syncope (r = 0.86, p = 0.012). Finally, hemodynamic changes during symptoms were compared between the 2 tests.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585865 TI - Single-plane transesophageal echocardiography for assessing function of mechanical or bioprosthetic valves in the aortic valve position. AB - To assess the value and limitations of single-plane transesophageal echocardiography in the evaluation of prosthetic aortic valve function, 89 patients (69 mechanical and 20 bioprosthetic aortic valves) were studied by combined transthoracic and transesophageal 2-dimensional and color flow Doppler echocardiography. In the assessment of aortic regurgitation, the transthoracic and transesophageal echocardiographic findings were concordant in 71 of 89 patients (80%). In 8 patients, the degree of aortic regurgitation was underestimated by the transthoracic approach; in each case the quality of the transthoracic echocardiogram was poor. In 10 patients, transesophageal echocardiography failed to detect trivial aortic regurgitation due to acoustic shadowing of the left ventricular outflow tract from a mechanical valve in the mitral valve position. Transesophageal echocardiography was superior to transthoracic echocardiography in diagnosing perivalvular abscess, subaortic perforation, valvular dehiscence, torn or thickened bioprosthetic aortic valve cusps, and in clearly distinguishing perivalvular from valvular aortic regurgitation. Transesophageal echocardiography correctly diagnosed bioprosthetic valve obstruction in 1 patient, but failed to diagnose mechanical valve obstruction in another. In conclusion, transesophageal echocardiography offers no advantage over the transthoracic approach in the detection and quantification of prosthetic aortic regurgitation unless the transthoracic image quality is poor. Transesophageal echocardiography is limited in detecting mechanical valve obstruction and in detecting aortic regurgitation in the presence of a mechanical prosthesis in the mitral valve position. However, it is superior to transthoracic echocardiography in identifying perivalvular pathology, differentiating perivalvular from valvular regurgitation and in defining the anatomic abnormality responsible for the prosthetic valve dysfunction. Combined transthoracic and transesophageal examination provides complete anatomic and hemodynamic assessment of prosthetic aortic valve function. PMID- 1585866 TI - Risk of patent foramen ovale for thromboembolic events in all age groups. AB - The association between a patent foramen ovale (PFO) and thromboembolic events in young patients has been reported. Autopsy data suggest that a PFO may be present in 20 to 35% of the population. To further assess the role of a PFO in patients with possible thromboembolic events, precordial and transesophageal contrast echocardiography was performed in 104 consecutive patients (age range 16 to 84 years) presenting with a stroke, transient ischemic attack or peripheral artery embolus (group I). These patients were compared with 94 consecutive patients (age range 23 to 82 years) undergoing transesophageal echocardiography for other reasons (group II). A PFO was found in 22 patients; 9 of 35 (26%) with an event but no risk factor (group Ia), 10 of 69 (14%) with an event but a recognized risk factor (group Ib), and 3 of 94 control patients (3.2%) (group II) (group Ia vs II: relative odds 10:1, p less than 0.001; group Ib vs II: relative odds 5:1, p less than 0.01; and group Ia vs Ib: p = not significant). The detection of a PFO was not related to age. The relatively low prevalence of a PFO in this study may reflect patient selection, but other explanations include: (1) Transesophageal contrast echocardiography may be relatively insensitive for its detection; (2) the prevalence in the general population may have been overestimated; and (3) most PFOs are very small, clinically insignificant and undetectable with this technique.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585867 TI - Minimally invasive management of transposition of the great arteries in the newborn period. AB - This study reports on a predominantly noninvasive management program for neonatal transposition of the great arteries [TGA] incorporating balloon atrial septostomy [BAS] under echocardiographic control. BAS was performed in 25 consecutive patients presenting with TGA between April 1988 and April 1990. Structural and coronary anatomy was evaluated echocardiographically with angiographic supplementation only when additional data were required. This information was correlated, where possible, with direct anatomic findings and subsequent course. BAS was performed through the umbilicus in 17 patients (85% of patients in whom this approach was attempted). Thirteen patients did not require ventilation during BAS. There were minimal complications and satisfactory septostomies in all cases. Coronary anatomy was correctly predicted in all patients where anatomic correlation was available. Without invasive investigation 9 patients underwent neonatal arterial switch procedures and 2 underwent palliative procedures. BAS under echocardiographic control proved safe, effective, minimally traumatic and mostly possible via the umbilical vein. The umbilical vein, where patent, permitted rapid safe access for BAS. Echocardiographic diagnosis of the coronary artery, and structural and functional anatomy was reliable and allowed minimally invasive preoperative management in many patients. PMID- 1585868 TI - Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group. AB - Electrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29% in the entire cohort, 19% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease. PMID- 1585869 TI - Normalization of upright exercise hemodynamics and improved exercise capacity one year after orthotopic cardiac transplantation. AB - The mechanisms of improved functional capacity over the first year after cardiac transplantation are not well studied. To assess the contribution of cardiac changes to this improvement, the serial evolution of upright rest and exercise hemodynamics during graded upright bicycle exercise was studied in 17 patients at 3 and 12 months after heart transplantation. Heart rate responsiveness, reflected by rapid heart rate acceleration on sitting and rapid deceleration after exercise, developed in the first year. Pulmonary capillary wedge pressure was lower at 1 year, both at rest and at peak exercise (10 +/- 3 vs 13 +/- 5 mm Hg at rest supine and 14 +/- 6 vs 18 +/- 8 mm Hg at peak exercise, p less than 0.05). Similarly, right atrial pressures were also significantly lower at 1 year (4 +/- 2 vs 6 +/- 3 mm Hg at rest supine and 6 +/- 5 vs 11 +/- 5 mm Hg at peak exercise, p less than 0.05). Cardiac index at peak exercise was greater at 12 months (6.4 +/- 1.3 vs 5.8 +/- 0.8 liters/min/m2, p less than 0.05), mediated primarily by higher exercise heart rate (135 +/- 16 vs 125 +/- 12 beats/min, p less than 0.05). In the first year after heart transplantation, improved rest and exercise hemodynamics and heart rate responsiveness contribute significantly to the improved functional capacity observed in these patients. PMID- 1585870 TI - Dependency of arterial compliance on circulating neuroendocrine and metabolic factors in normal subjects. AB - Reduced arterial compliance is now recognized as a feature of hypertension. Similarly, metabolic factors such as insulin, catecholamines and lipids are also associated with hypertension. This study explores the possibility that these neuroendocrine and metabolic factors may separately influence arterial compliance. Proximal compliance (aorta and large arteries) and distal compliance (small arteries and arterioles) were measured in 57 volunteers (30 hypertensive and 27 normotensive subjects, mean age 45 years). Compliance was quantified by analysis of arterial pulse wave contours obtained intraarterially together with hemodynamic estimates. Proximal compliance correlated with plasma insulin (r = 0.49; p less than 0.001), norepinephrine (r = -0.50; p less than 0.002), triglycerides (r = -0.39; p less than 0.01), total cholesterol (r = -0.33; p = 0.02) and high-density lipoprotein cholesterol (HDL) (r = 0.37; p less than 0.02). Similarly, distal compliance correlated with insulin (r = -0.37; p less than 0.02), triglycerides (r = -0.39; p less than 0.01), total cholesterol (r = 0.38; p less than 0.01) and HDL (r = 0.51, p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585871 TI - Slope of the end-systolic pressure-volume relation derived from single beat analysis is not always sensitive to positive inotropic stimuli in humans. AB - Single beat estimation of the slope of the end-systolic pressure-volume relation assumes symmetric left ventricular pressure increase and decay and requires extrapolation of peak isovolumic developed pressure (Pmax) from the left ventricular pressure curve of an ejection contraction. To test the sensitivity of this slope to positive inotropic stimuli, biplane cineangiocardiography and simultaneous high-fidelity left ventricular pressure measurements were performed in 50 patients with heart disease. The end-systolic pressure-volume relations were assessed under baseline conditions and during norepinephrine infusion (n = 19) or after postextrasystolic potentiation (n = 24), or both (n = 7). Norepinephrine did not change left ventricular end-systolic volume despite significant elevations of end-systolic pressure. Postextrasystolic potentiation significantly decreased end-systolic volume in association with an unaltered left ventricular end-systolic pressure. The potentiation significantly decreased the pressure half-time of contraction, an index of the speed of the left ventricular pressure increase, while it increased the pressure half-time of relaxation, an index of the speed of the pressure decline, indicating asymmetric pressure increase and decay. The slope of the end-systolic pressure-volume relation increased from 3.3 to 4.4 mm Hg/ml/m2 (p less than 0.001) during norepinephrine infusion. In contrast, despite an augmented contractility, the slope decreased significantly from 3.2 to 2.4 mm Hg/ml/m2 (p less than 0.0001) after the potentiation. The slope showed a high correlation with Pmax (r = 0.86, p less than 0.0001, n = 107). Thus, the slope of the end-systolic pressure-volume relation derived from single beat analysis is not always sensitive to inotropic interventions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585872 TI - Validity of cardiac output measurement by computer-averaged impedance cardiography, and comparison with simultaneous thermodilution determinations. AB - The accuracy and reproducibility of noninvasive cardiac output determinations by computer-averaged impedance cardiography were compared with those of simultaneously performed thermodilution cardiac output. In all, 43 patients (14 men and 29 women = 201 pairs) were studied by simultaneously performed impedance and thermal determinations. Individual impedance values correlated with paired thermodilution determinations (r = 0.75; p less than 0.0001). Each patient's average thermodilution values correlated with the average impedance values (r = 0.86; p less than 0.0001). Mean thermodilution output was 4.6 +/- 1.37 liters/min. Mean impedance output was 4.5 +/- 1.27 liter/min Reproducibility was comparable for impedance (0.0059 +/- 0.639) and thermodilution cardiac output (0.023 +/- 0.556). There was high agreement between methods by plot of the difference against mean of the 2 methods. Impedance cardiac output values agree and correlate highly with quality-controlled thermodilution outputs across a wide range of clinical conditions and hemodynamic values. PMID- 1585873 TI - Time for a prospective, randomized trial of the "open artery hypothesis" in survivors of acute myocardial infarction. PMID- 1585874 TI - Detection of complex intimal flaps in aortic dissection by transesophageal echocardiography. PMID- 1585875 TI - Clinical features and management of young patients with cardioinhibitory response during orthostatic testing. PMID- 1585876 TI - Cause and impact of pulmonary hypertension in isolated aortic stenosis on operative mortality for aortic valve replacement in men. PMID- 1585877 TI - Clinical evaluation of observations in poorly contracting and nondilated left ventricles (nondilated cardiomyopathy). PMID- 1585878 TI - Intravenous administration of monoclonal antibody to the platelet GP IIb/IIIa receptor to treat abrupt closure during coronary angioplasty. PMID- 1585879 TI - Calibration using angiographic catheters as scaling devices--importance of filming the catheters not filled with contrast medium. PMID- 1585880 TI - Frozen cadaver. Antemortem versus postmortem. AB - Three categories of skin from Hanford miniature swine were examined microscopically: normal, unfrozen skin; skin exposed to -75 degrees C air for 5 min, 6 h postinjury; and skin frozen postmortem. Frostbitten skin (antemortem freezing) was characterized grossly by a purple discoloration and microscopically by dilated, blood-filled, superficial capillaries. Other changes in the frostbitten skin were vacuolated epithelial cells and dermal edema. Unfrozen skin (controls) and skin frozen postmortem were more difficult to differentiate. However, the epidermis of the latter usually was compressed and more basophilic. We concluded that skin frozen antemortem could be separated from skin frozen postmortem by its intense hyperemia, characterized grossly as a purple discoloration and microscopically by engorged capillaries. PMID- 1585881 TI - Liver and spleen ruptures in authentic car-to-car side collisions with main impact at front door or B-pillar. AB - Seventy-nine belt-protected front seat occupants sustained authentic car-to-car side collisions with impact at front door or B-pillar in which energy equivalent speed (EES) and delta V had a highly significant influence on the occurrence of liver and spleen ruptures. From an EES greater than or equal to 40 km/h the risk of suffering liver and spleen injuries proved to be much higher for occupants on the impact side. Drivers on the impact side often had combined liver and spleen ruptures, front seat passengers had only liver ruptures and combined liver and spleen ruptures. The number of rib fractures on the left or right had a highly significant influence on the occurrence of liver and spleen ruptures. Liver ruptures and combined liver and spleen ruptures were often combined with pelvic ruptures. PMID- 1585882 TI - Reye's syndrome. A diagnosis occasionally first made at medicolegal autopsy. AB - Reye's syndrome, a condition characterized pathologically by cerebral edema and fatty change of the liver, has been described extensively in the medical literature as a disease manifested clinically by encephalopathy and coma. This is a report of five cases of Reye's syndrome occurring as sudden, unexpected deaths outside of the hospital. In each of these cases, there is a vague history of a previous viral illness. A history of aspirin intake is inconstant. Each child either had no significant past illnesses or there was a history of repeated upper respiratory infections. The classic progression of signs and symptoms usually described for Reye's syndrome, where vomiting usually precedes encephalopathy and coma, was not present in any of the cases. Results of autopsies showed the characteristic findings for Reye's syndrome, and additional tests showed no other explanation for the deaths. This manifestation of the disease is seldom described in medical literature, but it may be encountered occasionally by the medical examiner. PMID- 1585883 TI - Rapid death due to group A streptococcal infections. Necrotizing fasciitis and acute bacterial myositis. AB - Soft tissue infections due to the group A Streptococcus are difficult to diagnose and rapidly fatal. They may present to the forensic pathologist as an "obscure autopsy". Death may occur within or outside the hospital and with or without a history of fulminant infection or predisposing factors. It is important for the pathologist to exclude this condition through awareness of its existence and by appropriate dissection with retention of materials for microbiological and histological examination. PMID- 1585884 TI - Importance of information in forensic toxicology. AB - Information in forensic toxicology plays a very important role. The forensic pathologist usually seeks toxicologic analyses on basis of the information available at the time of the medicolegal autopsy. Such information may be obtained from different sources: hospitals, authorities, relatives, friends, or neighbors of the deceased and, obviously, macroscopic findings at the time of the autopsy. In order to evaluate the relative importance of these different sources of information, the authors have studied, retrospectively, results of 580 postmortem examinations performed at the Institute of Legal Medicine of Lisbon, wherein toxicologic analyses had been requested. These cases pertain to the years 1987 and 1988, but do not include alcohol determination in the blood in cases of traffic accidents. In 274 (47.4%) of the 580 cases, there were positive findings while in the remaining 306 (52.6%) findings were negative. In cases with positive findings, circumstances and factors, which may have influenced the pathologist's decision to request toxicologic analysis, are discussed. In more than half the cases, hospital information was the decisive factor, while in approximately 25% of the cases, autopsy findings were the justification. In contrast, it is worth mentioning that in approximately 45% of the cases with analytical negative results, requests were made, in cases of blank autopsies, for toxicologic analyses in order to exclude the possibility of poisoning. It is interesting to note that in the same proportion requests were justified on grounds of hospital information. Some of the factors that may explain this apparent discrepancy are discussed. Finally, the relevance of background information is emphasized at the level of the interpretation of analytical results, whether positive or negative.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585885 TI - National Association of Medical Examiners Pediatric Toxicology Registry. Report 1: Phenylpropanolamine. PMID- 1585886 TI - Lethal effects of normeperidine. AB - Normeperidine, having a longer half-life than meperidine, can accumulate faster. Its excitatory neurotoxicity is manifest with administration of multiple meperidine doses or in cases of renal failure. This is a report of the lethal effects of normeperidine in a patient with renal failure who had abused meperidine. PMID- 1585887 TI - Homicides in Auckland, New Zealand. A 14-year study. AB - In the 14-year period from 1976 to 1989, there have been 174 homicide victims in the Auckland colonial area. Data accessed from autopsy and police reports show that victims of marital conflict, family dispute, and arguments developing between nonmarried couples made up the largest proportion of homicide cases. Stabbing and assault with a blunt weapon were the most common causes of death. The data also show that homicide is relatively uncommon in Auckland in comparison with other cities of similar size. PMID- 1585888 TI - Morphometric analysis of the dental pulp chamber as a method of age determination in humans. AB - Eighty bite-wing radiographs from 40 female and 40 male patients were selected from the patient record system at the University of Texas Dental School at San Antonio, Texas. All samples were equally divided into four age groups, with a range from 15 to 55 years of age. The lower right first permanent molar tooth was chosen as the representative tooth for measuring the maximum height and width of the pulp chamber. The reproducibility of the method was checked by repeating all measurements on two different occasions. Regression analysis indicates that the height and width of the pulp chamber were negatively correlated with age (height r = -0.376 and width r = -0.125). The coefficient of determination (r2) for pulp chamber height and width were 0.123 and 0.058, respectively. This indicates that although there appears to be a definite relationship between the age of an individual and the height and width of the dental pulp chamber, these measures cannot be used as a reliable method of age determination. PMID- 1585889 TI - Comparison of the battles at the Little Bighorn and at Isandhlwana. Medicolegal and forensic aspects. AB - Compared are two great and remarkably similar battles that occurred less than 3 years apart: the U.S. Cavalry versus the Plains Indians in the battle at the Little Bighorn in Montana Territory of the United States, and the British-Zulu battle at Isandhlwana in the Natal Province of South Africa. Computer evaluation, which was especially helpful in evaluating artifacts at the Montana site, could be an excellent tool to use in other such large-scale investigations. PMID- 1585890 TI - Tattoos and tattooing. Part II: Gross pathology, histopathology, medical complications, and applications. AB - Tattooing involves piercing the skin with needles bearing various pigments, to cause the permanent imprint of a design. The body responds to these incursions in specific and predictable ways, with initial sloughing of the overlying epidermis, variable dermal inflammation, and gradual assimilation of the pigment into macrophages. Eventually, much of the pigment is carried to the regional draining lymph nodes, with a residue staying within macrophages localized to dermal perivascular regions. The age of tattoos may be estimated, both grossly and microscopically. Tattooing can result in a variety of relatively uncommon complications and adverse reactions to the pigment, and certain infectious diseases may be inadvertently transmitted through tattooing when the instruments are inadequately sterilized, or when poor technique is used. This article, the second of three, describes the gross and microscopic pathology of both fresh and healed tattoos, and discusses the various complications (infectious and otherwise) that can occur. Tattooing has specific applications in both dermatology and plastic and reconstructive surgery, and these are also discussed. PMID- 1585891 TI - Dirty diving. Sudden death of a SCUBA diver in a water treatment facility. AB - We report a case of a sudden death in a SCUBA diver working at a water treatment facility. The victim, an employee of the facility with a specialty in electronics, was a sport diver not qualified in commercial diving. While attempting to clean sludge from a blocked drain 25 ft under water, the diver was suddenly pinned against the drain valve when the sludge plug was broken up. We review the mechanics of the incident and the actual cause of death, asphyxia, as opposed to drowning. We believe this to be the first reported case of traumatic (pressure) asphyxia in a SCUBA diver. PMID- 1585892 TI - Two-man and two-sibling paternity cases. AB - Traditional genetic marker systems rarely fail to resolve paternity disputes when two or more men are accused, except when men are brothers. A sibling of the biologic father may not be excluded by these laboratory tests and sometimes yields calculated odds of paternity that are equal to or higher than the true male parent. Resolved two-brother cases were compared with resolved cases involving two unrelated men. In each case, the residual odds of paternity were determined for each man and the greater was divided by the lesser to produce a paternity fraction. The paternity fraction is a useful indicator of biologic parentage when it exceeds a value of 10 (log10 of-the-odds score greater than or equal to 1). Tests for alleles at highly heterozygous loci are indicated in initial laboratory evaluations of cases involving brothers. Human leukocyte antigen and variable number of tandem repeat polymorphisms appear suitable. PMID- 1585893 TI - Paper strip screening method for detection of cyanide in blood using CYANTESMO test paper. PMID- 1585894 TI - Head injuries from short distance falls. AB - The problem of evaluating injury in childhood as to causation--accidental, inflicted or other--is compounded by conflicting literature. The child presenting with head injury following a short distance fall should be a source of alarm. Some of the key thoughts in the literature are evaluated with presentation of some additional observations, in an attempt to sort out some apparent conflicts. PMID- 1585895 TI - Gunshot residue, ten years later. PMID- 1585896 TI - Does cigarette smoking make you ugly and old? AB - During the last 20 years, at least five studies have examined the association between cigarette smoking and facial wrinkling. Although there are methodological concerns with each of these studies, the data are consistent with the conclusion that smoking causes skin wrinkling that could make smokers appear unattractive and prematurely old. Cigarette smoking has been shown to decrease capillary and arteriolar blood flow in the skin, perhaps damaging connective tissue components that are important to maintaining the integrity of the skin. Americans are highly motivated to avoid or eliminate facial wrinkles. The association of smoking and facial wrinkling may be important evidence to convince young persons not to begin smoking and older smokers to quit. PMID- 1585897 TI - Asbestos and colon cancer: lack of association in a large case-control study. AB - Previous studies linking exposure to asbestos with human colon cancer have used mortality rather than incidence as their endpoint and have neither assessed nor controlled for confounding by diet, genetic factors, or other risk factors for colon cancer. A case-control study of 746 histologically confirmed cases of colon cancer and 746 matched neighborhood controls was conducted in Los Angeles County, California. In univariate analyses of the 419 male pairs, a weak association was found between asbestos exposure and colon cancer (odds ratio (OR) = 1.16, 95% confidence interval (CI) 0.80-1.69). When confounding by family history of large bowel cancer, diet, body weight, and physical activity was controlled, there was no association between colon cancer and exposure to asbestos among males (OR = 0.99, 95% CI 0.66-1.50). When asbestos exposure was restricted to occurrences preceding diagnosis by more than 15 years, there was no clear association between such exposure and colon cancer, either before (OR = 1.14, 95% CI 0.76-1.70) or after confounding was controlled (OR = 0.93, 95% CI 0.60-1.44). Further analyses by frequency and duration of exposure failed to show any association between asbestos and risk of colon cancer, but did show a consistent pattern of confounding by nonoccupational factors that, when controlled, invariably produced a weak protective effect of asbestos exposure. Among the 327 female pairs, only 6 cases and 11 controls reported asbestos exposure (OR = 0.55, 95% CI 0.20-1.48), and there was no evidence of risk increasing as the frequency or duration of exposure increased. This study suggests not only that occupational exposure to asbestos is not a risk factor for colon cancer in the general population of Los Angeles, but also that observed associations between asbestos and colon cancer should not be interpreted as causal unless confounding by nonoccupational factors has been evaluated and controlled. PMID- 1585898 TI - Myocardial infarction and coronary death among women: psychosocial predictors from a 20-year follow-up of women in the Framingham Study. AB - This study investigates the relation of psychosocial variables to the 20-year incidence of myocardial infarction or coronary death among women in the Framingham Study. In 1965-1967, a psychosocial interview was given along with the collection of other coronary risk factor data. This study includes 749 women aged 45-64 years who were free of coronary disease at this baseline examination. Demographic variables, psychosocial scales (such as tension and reactions of anger), and individual interview items (such as attitudes toward children, money, and religion) were measured. When age, systolic blood pressure, the ratio of serum total cholesterol to high-density lipoprotein cholesterol, diabetes, cigarette smoking, and body mass index were controlled for in multivariate proportional hazards models, the predictors of the 20-year incidence of myocardial infarction or coronary death were as follows: among employed women, perceived financial status only; among homemakers, symptoms of tension and anxiety, being lonely during the day, difficulty falling asleep, infrequent vacations, housework affecting health, and believing one is prone to heart disease (p less than 0.05 for all variables); and among both groups of women combined, low educational level, tension, and lack of vacations. These results are discussed in relation to previous findings from the Framingham Study. PMID- 1585899 TI - Nonparticipation as a determinant of adverse health outcomes in a field trial of oral cholera vaccines. AB - The authors estimated the incidence rates of cholera and death between 1985 and 1988 for 32,642 age- and sex-eligible persons who did not participate in a randomized, placebo-controlled field trial of killed oral cholera vaccines in rural Bangladesh. As compared with 20,744 placebo recipients, the relative risk of cholera for all nonparticipants, adjusted for potentially confounding demographic variables, was 1.20 (95% confidence interval (CI) 1.03-1.41); this adjusted relative risk reflected elevated adjusted relative risks in nonparticipants who were medically ineligible (RR = 1.65; 95% CI 1.22-2.22) or refused to participate (RR = 1.19; 95% CI 1.01-1.41), but not in persons absent at the time of vaccination (RR = 1.00; 95% CI 0.78-1.28). The adjusted relative risk of death was also elevated in nonparticipants as compared with placebo recipients (RR = 1.28; 95% CI 1.10-1.48), with the same pattern of adjusted relative risks for different categories of nonparticipants: for ineligible subjects, 2.64 (95% CI 2.12-3.29); for refusers, 1.20 (95% CI 1.02-1.41); and for absentees, 0.95 (95% CI 0.75-1.22). The authors concluded that nonparticipation was associated with clinically cogent adverse health outcomes, but that the magnitude of these associations varied according to the reason for nonparticipation. These findings underscore the caution required in assessing vaccine efficacy with controls who are not vaccinated because of choices made by patients or vaccinators. PMID- 1585902 TI - Cigarettes, coffee, and preterm premature rupture of the membranes. AB - Premature (prior to 37 completed weeks of gestation) rupture of the membranes (preterm PROM) is one of the most common underlying causes of preterm delivery. However, there have been few epidemiologic studies of this obstetric complication. The authors studied the relation of maternal cigarette smoking and coffee consumption to both preterm PROM and spontaneous preterm labor not complicated by premature rupture of the membranes (preterm NONPROM) in a large cross-sectional data base. The 307 preterm PROM and 488 preterm NONPROM cases who delivered during 1977-1980 at the Boston Hospital for Women were compared with 2,252 randomly selected women who delivered at term at that institution. Multiple logistic regression techniques were used to derive maximum likelihood estimates of adjusted odds ratios (OR) and 95% confidence intervals (CI). After confounders had been adjusted for, the relative risk of preterm PROM for women who reported ever having smoked during pregnancy, as compared with nonsmokers, was 1.6 (95% CI 1.1-2.4). However, no gradient between the number of cigarettes smoked per day and the risk of preterm PROM was observed. Similar results were observed for preterm NONPROM. Women who consumed three or more cups of coffee daily during the first trimester had a 2.2-fold greater risk of preterm PROM than did women who drank two or fewer cups (95% CI 1.5-3.3). Among coffee drinkers, there was some evidence of a linear trend in the risk of preterm PROM as coffee consumption increased. Consumption of three or more cups of coffee per day was less strongly associated with the occurrence of preterm NONPROM (adjusted OR = 1.4, 95% CI 1.0 1.9). PMID- 1585901 TI - Sexual behavior and status for human immunodeficiency virus type 1 among homosexual and bisexual males in Mexico City. AB - The authors examined sexual behaviors, the seroprevalence of human immunodeficiency virus type 1 (HIV-1), and condom use among 2,314 homosexual and bisexual men tested during 1988-1989 at the AIDS (acquired immunodeficiency syndrome) National Center in Mexico City. Bisexuals constituted 24% of the sample; the seroprevalence rate was lower for bisexuals than homosexuals (21 vs. 34%). In logistic regressions, HIV-1 seropositivity was independently related to age, education, pattern of insertive/receptive behavior in anal sex, lifetime number of male sex partners, having sex with someone with AIDS, homosexual versus bisexual behavior, and a history of condyloma. The same logistic regressions were found to fit bisexuals and homosexuals. The rate of HIV-1 was reduced in individuals who indicated always requiring their partners to use a condom when practicing receptive anal sex (1% of the total). The most common practice for both homosexuals and bisexuals was "mixed" behavior (i.e., both insertive and receptive anal sex); this was also the practice with the highest risk. Bisexuals practiced both vaginal and anal sex with women and reported little condom use. The substantial seroprevalence among bisexuals, their frequent sexual contact with women, and their low rate of condom use imply a continuing role as a bridge of infection to females. Whether this risk will lead to a sustained heterosexual epidemic remains to be determined. PMID- 1585900 TI - Epidemiology of taeniasis and cysticercosis in a Peruvian village. The Cysticercosis Working Group in Peru. AB - To determine the prevalence of cysticercosis in a rural area where the disease is endemic, the authors studied the seroepidemiology of human and porcine cysticercosis in a Peruvian jungle community (Maceda, Peru) in 1988 using an enzyme-linked immunoelectrotransfer blot (EITB) assay. Of the 371 sampled inhabitants, 30 (8%) were seropositive, most of whom were asymptomatic. After niclosamide therapy, four Taenia species worms were identified in the seropositive group, compared with one in the control group (p = 0.06). Pigs were frequently infected: 44 of 133 (33%) were found positive for Taenia by tongue examination and 57 of 133 (43%) were positive by EITB. In 69% of the sampled households that had pigs, there was at least one seropositive pig. The number of pigs diagnosed positive by the tongue examination was significantly greater in households that had latrines than in those that did not. Cysticercosis is a common but usually asymptomatic infection that affects both humans and pigs in the high jungle areas of Peru. PMID- 1585904 TI - Time trends in physical activity among college alumni, 1962-1988. AB - Little direct evidence exists in the epidemiologic literature to support the widely held belief that an individual's physical activity behavior varies over the years. To provide data, the authors prospectively studied patterns of physical activity among 6,092 Harvard College alumni (average age at the start of follow-up, 43 years) who responded to questionnaires in 1962 or 1966, 1977, and 1988, and who declared themselves free of cardiovascular disease and cancer throughout that period. The median energy expenditure increased between 1962 or 1966 and 1977, but stabilized between 1977 and 1988. However, rank correlation coefficients between estimates of energy expenditure in 1977 and 1988 ranged from 0.36 to 0.41 for the various age groups (compared with 0.81-0.84 for the Quetelet index, and 0.60-0.65 for the current number of cigarettes smoked per day), implying that physical activity at the individual level was not constant. For 4,238 alumni for whom data on collegiate sports participation were available, the rank correlation coefficients between collegiate activity and alumni activity 1-7 decades later were even lower, ranging from 0.05 to 0.17 (compared with 0.31-0.58 for the Quetelet index). Thus, physical activity assessed over a short time period in an individual may not be a valid proxy for activity over the long term. The characteristics that distinguished alumni who consistently expended less than 1,000 kcal/week (in climbing stairs, walking, and playing sports) in 1962 or 1966, 1977, and 1988 from those who consistently expended greater than 2,500 kcal/week were as follows: at baseline, older age, overweight, and cigarette smoking; and during college, not having been a varsity athlete and fewer hours playing sports. PMID- 1585903 TI - The mediating effect of maternal nutrition knowledge on the association between maternal schooling and child nutritional status in Lesotho. AB - The present study tested whether maternal nutrition knowledge was a mediating factor in the association between maternal schooling and child nutritional status, and whether the mechanism involved differed according to socioeconomic status. The data were collected in Lesotho on 921 mother-child pairs and included scores from a nutrition knowledge test, socioeconomic and demographic information, and the child's anthropometric data. A wealth factor derived from a factor analysis was used to stratify the sample into two socioeconomic groups. Two-stage least-squares estimation was used to test the mediating role of nutrition knowledge between maternal schooling and child weight-for-age. Results showed that both the importance of maternal schooling and the mechanism by which it affects the child's weight-for-age are contingent upon the family's socioeconomic status. While maternal schooling was positively associated with weight-for-age for both wealthier and poorer households, the size of the effect was much larger for the latter group. The effect of maternal schooling on weight for-age was mediated by the mother's nutrition knowledge only among wealthier households. These results imply that, in Lesotho, nutrition education for mothers could contribute to improving children's growth, but only in households that have access to a minimum level of resources. For poorer households, nutrition education would not be sufficient. PMID- 1585905 TI - Assessing the direction of causality in cross-sectional studies. AB - Interpretation of observational studies is difficult, particularly in cross sectional studies, because the direction of cause and effect may be difficult to assess: Did the "outcome" affect the measured exposure level, or did the exposure affect the outcome? In this paper, the authors describe a pattern, the "checkmark pattern," which can arise in cross-sectional studies. This pattern is characterized by higher levels of the outcome in an unexposed comparison group than in some subgroups of the exposed. The pattern, if seen in certain types of observational studies, suggests that the "outcome" variable may have affected the measured exposure level. Recognition of the pattern may help the epidemiologist to decipher the causal sequence. Two examples illustrate the issues involved. PMID- 1585906 TI - The circadian rhythm of the perinatal mortality rate in Switzerland. AB - The authors examine the relation between the perinatal mortality rate (PMR), birth weight in four categories, and hour of birth throughout the week in Switzerland, using data on 672,013 births and 5,764 perinatal deaths recorded between 1979 and 1987. From Monday to Friday, the PMR follows a circadian rhythm with a regular increase from early morning to evening, with a peak for babies born between 7 and 8 p.m. This pattern of variation has two main components: The circadian rhythms for the proportion of births in the four weight categories and the PMR circadian rhythm for babies weighing more than 2.5 kg. According to a cosinor model, which describes about 40% of the total variation in the PMR, the most important determinants are changes in the proportions of births: Low birth weight increases toward the afternoon and night. Mechanisms underlying the weight specific timing of birth are discussed, including time selection of birth according to obstetric risks, the direct effect of neonatal and obstetric care, and chronobiologic behavior. PMID- 1585907 TI - Thrombotic thrombocytopenic purpura in patients with human immunodeficiency virus infection: a report of three cases and review of the literature. AB - Three cases of thrombotic thrombocytopenic purpura (TTP) and coexistent human immunodeficiency virus (HIV) infection are presented with a review of 15 cases reported in the literature. Of the 18 total patients, one-half presented with no symptoms of HIV infection while nine patients presented with symptomatic HIV disease before or simultaneous to the diagnosis. The presenting symptoms were similar to those with classic TTP and included fever in 75% and 40% with neurologic symptoms. Laboratory parameters reflected the microangiopathic hemolytic anemia typically seen in patients with TTP. The median hematocrit was 19.4%, while the median platelet count was 16,000/mm3. As with classic TTP, patients with HIV-related TTP only had mild renal dysfunction (median creatinine of 1.2 mg/dl, range 0.8-4.8 mg/dl). Plasma exchange produced clinical remission in a majority of the patients. Importantly, approximately one-third of the patients died prior to the initiation of therapy. We conclude that TTP is a rare but treatable condition in patients with HIV infection. A TTP diagnosis should be considered in patients with HIV infection who present with severe anemia and thrombocytopenia. Plasma exchange should be considered as initial therapy. The role of both antiplatelet therapy and aspirin is unknown. PMID- 1585908 TI - Splenic sequestration associated with sickle cell trait and hereditary spherocytosis. AB - Coexistence of sickle cell trait and hereditary spherocytosis (HS) is unusual, and only 16 cases have been reported in the literature. These patients have the same clinical and hematological features as individuals having HS alone. We report a serious complication, acute splenic sequestration crisis (ASSC), occurring in two patients with sickle cell trait and HS. One patient experienced four episodes of ASSC during an 11-year span, while the other had two episodes of this complication during a 4-year period. Red blood cell studies and membrane protein analysis confirmed the diagnosis of HS as a consequence of spectrin deficiency. Splenectomy resulted in marked clinical and hematological improvement in both patients. Histological examination of spleens following splenectomy confirmed that significant erythrostasis and sickling had indeed occurred. ASSC can occur in patients with coexistence of sickle cell trait and HS, and this potentially life-threatening complication should be considered in this condition. PMID- 1585909 TI - On laboratory problems in diagnosing mild von Willebrand's disease. AB - By providing some examples of variations in the levels of von Willebrand factor antigen (vWF:Ag), ristocetin cofactor, and Factor VIII during one month, the authors wish to emphasize the difficulty of diagnosing mild forms of von Willebrand's disease (vWD), especially type I. In three of 15 normal female volunteers the vWF:Ag levels, on some sampling occasions, were so low (0.25-0.30 IU/mL, normal greater than 0.50 IU/mL) that the diagnosis of vWD type I might be made while on other occasions normal levels were obtained. The coefficients of variation (CV) for vWF:Ag in these three women were 12%, 25%, and 43%. However, CVs of similar magnitude were also observed for "non-diseased" males and females. The ratio F VIII/vWF:Ag also varied greatly. In the three women with suspected vWD it was 36%, 15%, and 34%. A representative level for the entire cycle of vWF:Ag and ristocetin cofactor seems to have been obtained in the follicular phase and therefore it is suggested that in order to make the diagnosis of vWD type I, at least in females, blood samples should be taken in this phase. PMID- 1585910 TI - Cephalosporin-induced hemolysis: a case report and review of the literature. AB - Cephalosporins are commonly used drugs that interact with red blood cell membranes. They frequently cause a positive direct antiglobulin test but rarely cause hemolysis. A case of cefotetan-induced hemolytic anemia is described in which two types of antibodies were detected. One reacted with red blood cells by a hapten mechanism, the other reacted with drug to form immune complexes. This case is compared with the 13 cases of cephalosporin-induced hemolytic anemia reported to date. Understanding the interactions of red blood cells and cephalosporins is critical to the safe use of these commonly prescribed drugs. PMID- 1585911 TI - A study of lymphoma of large granular lymphocytes with modern modalities: report of two cases and review of the literature. AB - Two cases of lymphoma of large granular lymphocytes are reported. The first case expressed natural killer (NK) cell, some T-cell (CD 2, CD 5, CD 8), and HLA-DR antigens, but was negative for other T-cell (CD 3, CD 4, CD 7), T-cell receptor (TCR), B-cell, and myeloid antigens. Germline configuration was demonstrated for TCR, and immunoglobulin heavy and light chain genes. The second case expressed NK cell, some T-cell (CD 3, CD 7, CD 8), and TCR antigens, but was negative for other T-cell (CD 4, CD 5), B-cell, myeloid, and HLA-DR antigens. Rearrangement of TCR alpha and beta chains were detected. Thus, the findings of case 1 were consistent with true NK cell lineage and case 2 with NK-like T-cell lineage. Our report underscores the heterogeneity of this newly recognized lymphoma, which nevertheless carries a consistently poor prognosis and is probably more prevalent in the Asian population. This study also provides information concerning immunophenotypes of cellular infiltrates in internal organs and cytogenetic abnormalities in this lymphoma; neither has been reported frequently in the literature. The importance of detecting cytoplasmic granules in tissue imprints or electron micrographs for differentiating other T-cell lymphomas is emphasized, and the classification of large granular lymphoproliferative disorders is discussed. PMID- 1585912 TI - Effect of red blood cells from patients with sickle cell disease on platelet factor 3 release. AB - Red cells from two SS genotype and two SA genotype patients were sampled. When the samples were deoxygenated and mixed with platelet-rich plasma, they caused the release of platelet factor 3 as recorded in a coagulometer. This phenomenon was not present in control blood samples from normal individuals. Membrane changes in abnormal red cells during hypoxia may be responsible in part for platelet activation and its role in vasoocclusive crisis. Vasoocclusive crisis could be prevented by increasing the red cell membrane fluidity and inhibiting the platelet aggregation with pentoxifylline. PMID- 1585913 TI - Acquired von Willebrand disease: correction of hemostatic defect by high-dose intravenous immunoglobulins. AB - High-dose intravenous immunoglobulins (ivIG) were used in a 57-year-old patient with acquired von Willebrand disease in order to correct a hemostatic defect before pneumonectomy for lung carcinoma. IvIG induced a rapid and complete correction of factor VIII (F VIII) and von Willebrand factor (vWF) and allowed surgery without additional factor coverage. F VIII and vWF returned to baseline values within 10 days after ivIG. PMID- 1585914 TI - High incidence of factor XI deficiency in Gaucher's disease. PMID- 1585915 TI - Erythropoietin levels in Gaucher patients. PMID- 1585916 TI - Irreversibility of drug resistance in VAD-refractory myeloma. PMID- 1585917 TI - Low-dose cytosine arabinoside as an alternative treatment for acute leukemia in Jehovah's Witnesses. PMID- 1585918 TI - Continuous infusion of highly purified factor VIII (Monoclate M) PMID- 1585919 TI - 12-Lipoxygenase and vascular disease. PMID- 1585921 TI - Change of paraprotein from IgA to k chain in multiple myeloma. PMID- 1585920 TI - Cyclosporin A used to reverse drug resistance increases vincristine neurotoxicity. PMID- 1585922 TI - Differential expressions of CD25 or CD71 on CD4+ and/or CD8+ tumor cells from a patient with adult T-cell leukemia/lymphoma: three color flowcytometric analysis of peripheral blood and lymph node. PMID- 1585923 TI - Treatment of relapsed or refractory Hodgkin disease and non-Hodgkin lymphoma with high-dose chemoradiotherapy followed by unstimulated autologous peripheral stem cell rescue. AB - Nine patients with relapsed or refractory Hodgkin disease or non-Hodgkin lymphoma underwent peripheral stem cell autografting because of a history of marrow involvement with visible lymphoma. Peripheral stem cells were collected during a process of unstimulated leukapheresis. Recovery to a neutrophil count of 0.1 x 10(9)/L was seen at a median of 14 days compared with a median of 18 days for a concurrent series of marrow recipients (P = .12). Recoveries to a neutrophil count of 0.5 x 10(9)/L and a platelet count of 50 x 10(9)/L occurred at medians of 25 days and 28 days, respectively. These figures are not significantly different from those obtained in the marrow recipients. Of the original nine patients, six are surviving free of disease progression or relapse at a median of 240 days posttransplant. Two patients died of transplant-related complications and one relapsed 250 days post-transplant. All surviving patients remain independent of transfusions and six have attained almost complete hematological reconstitution. Although administration of cytotoxic therapy and granulocyte macrophage colony-stimulating factor (GM-CSF) may enhance the yield of early progenitor cells during leukapheresis, unstimulated leukapheresis results in a stem cell product capable of rapidly restoring and sustaining marrow function even after multiple courses of intensive "salvage" therapy. Additional follow-up will be needed to determine whether preliminary survival figures continue to compare favorably with those of patients with similar extramedullary disease states undergoing marrow transplants. PMID- 1585924 TI - Differential expression of non-major histocompatibility complex-restricted cytotoxicity in patients with granular lymphocyte-proliferative disorders associated with or unassociated with severe anemia. AB - Of 27 patients with granular lymphocyte-proliferative disorders (GLPD), 18 patients had CD3+ T-cell-lineage GLPD (T-GLPD), and 9 patients had CD3-CD16+ natural killer (NK) cell-lineage GLPD (NK-GLPD). In 9 of the 18 patients with T GLPD, severe anemia of less than or equal to 7.5 g/dl hemoglobin (mean 5.4 g/dl) and erythroid hypoplasia in the bone marrow developed, while the remaining 9 patients with T-GLPD and 9 patients with NK-GLPD exhibited hemoglobin levels of greater than or equal to 10.0 g/dl, and erythroid hypoplasia was not found. The number of leukocytes, neutrophils, lymphocytes or granular lymphocytes in the peripheral blood, or the percentage of lymphocytes in the bone marrow did not differ significantly between the patients with T-GLPD associated with severe anemia and those with T-GLPD not associated with severe anemia, and the immunophenotypes of peripheral blood mononuclear cells (PBMC) were not significantly different either. However, when non-major histocompatibility complex (MHC)-restricted cytotoxicity was assayed with PBMC, T-GLPD patients with severe anemia and NK-GLPD patients exhibited significantly higher levels of non MHC-restricted cytotoxicity than T-GLPD patients without severe anemia. Because PBMC obtained from T-GLPD patients with severe anemia were shown not to lyse erythroblasts directly, the possibility that patient PBMC lyse erythroblasts in the bone marrow and thus cause anemia seems unlikely. The pathogenesis of anemia in GLPD was discussed. PMID- 1585926 TI - US minority groups and end-stage renal disease: a disproportionate share. PMID- 1585925 TI - End-stage renal disease in US minority groups. AB - Medicare's End-Stage Renal Disease (ESRD) Program makes renal replacement services accessible for the majority of Americans with renal failure. National data from Medicare demonstrate complex and variable patterns of use of renal replacement services among US racial and ethnic groups. The black population has consistently suffered from a greater than 3.5-fold higher rate of treated ESRD than has the white population. The rates of hypertensive, diabetic, and glomerulopathic ESRD are all substantially greater in blacks than in whites, and hypertension has accounted for a far greater proportion of ESRD in blacks than any other diagnosis. There is a paucity of national data on the occurrence of ESRD in Hispanic Americans. However, data from Texas strongly suggest that the incidence rate of treated ESRD is much higher in Mexican Americans than in non Hispanic whites. Higher rates are apparent for each of the three most important causes of ESRD: hypertension, diabetes, and glomerulonephritis. Native Americans experience ESRD at a rate intermediate between those of whites and blacks, but their rate of diabetic ESRD is higher than in either blacks or whites. However, considerable diversity exists among Native American tribal groups. Significant barriers to the acquisition of preventive care have been identified, especially for blacks. While these barriers to preventive care are accompanied by a significantly impaired health status of the black American population, a specific causal relationship between impaired access to care for blacks and their predisposition to ESRD has not been established. PMID- 1585927 TI - Race and sex differences in the identification of candidates for renal transplantation. AB - The availability of renal transplantation to individuals with end-stage renal disease (ESRD) is an issue of considerable concern. The role of age, race, sex, socioeconomic status, illness severity, and comorbidity in determining access to this therapy remains unclear. We examined the influence of these factors on transplant candidacy in 8,315 patients receiving dialysis treatment for ESRD in North Carolina, South Carolina, and Georgia. We found important race-sex differences in the likelihood of being identified as a transplant candidate. These differences persisted after adjustment for other patient characteristics, including illness severity and certain comorbid conditions. Characteristics found to be positively associated with candidacy included age less than 30 years (P less than 0.00001), living with a spouse and children (P = 0.004), and employment status (P = 0.006). Characteristics and comorbid conditions that were negatively associated with candidacy included 8 years or less of formal education (P = 0.001), cancer (P = 0.0006), visual impairment (P = 0.006), congestive heart failure (P = 0.008), and peripheral vascular disease (P = 0.01). Compared with white males, after adjustment for these factors, the likelihood (95% confidence interval) of being identified as a transplant candidate was: white females, 0.88 (0.65 to 1.18); black males, 0.77 (0.59 to 0.99); and black females, 0.66 (0.51 to 0.87). We conclude that although socioeconomic and medical factors are strongly associated with transplant candidacy, these associations do not adequately explain the observed race-sex differences in transplant candidacy status. PMID- 1585928 TI - Diltiazem enhances potassium disposal in subjects with end-stage renal disease. AB - Seven subjects with end-stage renal disease (ESRD) who were anuric and dialysis dependent were studied during a 28-hour interdialytic period to assess changes in plasma potassium. Plasma potassium, glucose, magnesium, aldosterone, and cortisol were measured every 4 hours. Eight normal subjects were similarly treated. Subjects with ESRD had a progressive increase in plasma potassium, in contrast to normal subjects who exhibited a characteristic diurnal variation. In ESRD, diltiazem significantly reduced the rate of increase in plasma potassium compared with placebo and resulted in a significantly lower net increase in potassium over the entire 28-hour period. Diltiazem did not affect plasma potassium in normal subjects. Diltiazem did not affect plasma aldosterone, cortisol, glucose, or magnesium. In conclusion, diltiazem reduced the rate of increase of plasma potassium during a 28-hour interdialytic period. PMID- 1585929 TI - Serum amyloid P component: a predictor of clinical beta 2-microglobulin amyloidosis. AB - Beta 2-microglobulin (beta 2M) amyloidosis is common in patients on long-term hemodialysis, but the clinical conditions associated with disease activity are poorly understood. This study was designed to determine if the serum amyloid P (AP) component concentration is predictive of beta 2M amyloid disease activity. Serum AP component concentrations were determined by rocket immunoelectrophoresis and beta 2M concentrations by a commercially available kit. Radiographic evidence of beta 2M amyloidosis was determined from bone films of the hips, shoulders, and hands. Serum AP component concentrations were not different in dialysis and control patients. However, AP component concentrations in long-term (greater than or equal to 5 years) dialysis patients were significantly lower than in short term (less than 5 years) dialysis patients (43.0 +/- 16.9 micrograms/mL [n = 28] v 56.0 +/- 18.3 micrograms/mL [n = 31], P less than 0.05). The patients on hemodialysis for 5 or more years who had radiographic evidence of severe beta 2 M amyloidosis were significantly older (57.9 +/- 9.5 v 38.3 +/- 11.3 years, P less than 0.001) and their serum AP concentrations were significantly lower (34.3 +/- 15.0 v 50.1 +/- 15.6 micrograms/mL, P less than 0.05) than long-term dialysis patients without radiographic evidence of disease. Stepwise regression analysis showed that the patient's age and serum AP component concentration were predictors of radiographic evidence of beta 2 M amyloidosis. Thus, serum AP component concentrations are decreased in long-term dialysis patients, suggesting accelerated deposition into amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585930 TI - The effects of reprocessing high-flux polysulfone dialyzers with peroxyacetic acid on beta 2-microglobulin removal in hemodiafiltration. AB - The reuse of dialyzers is widely practiced, especially in the United States. Despite this, the effects of reuse on the efficacy of removal of solutes and more recently proteins such as beta 2-microglobulin (beta 2M) are the subject of much debate. There is considerable evidence to suggest that reuse after cleansing and sterilizing with formalin, with or without bleach, maintains dialyzer performance. In this study, we have examined peroxyacetic acid use as the cleansing and sterilizing agent using Renatron machines. We analyzed reuse in 24 patients using polysulfone membranes in a hemodiafiltration (HDF) unit over a 2 year period. The mean maximum number of uses achieved was 20.1 +/- 0.5. Several factors considered clinically to influence the number of reuses achievable (hemoglobin, white blood cell, and platelet levels, erythrocyte sedimentation rate [ESR], and fibrinogen and total protein levels) were found not to influence the maximum number of uses obtainable. We then assessed prospectively the performance of 26 polysulfone dialyzers after peroxyacetic acid reprocessing up to 20 times, particularly with regard to their ability to remove beta 2M. We report that this combination of polysulfone membranes reprocessed with peroxyacetic acid used for HDF up to 20 times exhibits a maintained high level removal of compounds beyond a molecular weight (MW) of 12,000. Any secondary membrane formation that occurs appears not to influence the subsequent removal of beta 2M. Thus, we would recommend the use of peroxyacetic acid for reprocessing dialyzers in a safe and efficacious manner. PMID- 1585931 TI - An in vivo analysis of reverse ultrafiltration during high-flux and high efficiency dialysis. AB - We have developed an in vivo pressure monitoring system to study the phenomenon of reverse ultrafiltration of dialysate during high-flux and high-efficiency dialysis. Under the usual operating conditions of either type of dialysis, driving pressures existed for reverse ultrafiltration of dialysate into the venous end of the blood compartment. Whether or not reverse ultrafiltration could be abolished at higher ultrafiltration rates was dialyzer-dependent, being least with high-efficiency dialysis. In addition, the degree of reverse ultrafiltration was affected by patients hematocrit, dialyzer inlet and outlet oncotic pressures, and the rate and direction of dialysate flow. PMID- 1585932 TI - Anaphylactoid reactions during hemodialysis and hemofiltration: role of associating AN69 membrane and angiotensin I-converting enzyme inhibitors. AB - Over a 20-month period, we observed 15 anaphylactoid reactions in six patients undergoing hemodialysis and three others on hemofiltration with AN69 capillary dialyzers who were receiving angiotensin-converting enzyme (ACE) inhibitors. These reactions were severe in 11 cases. In eight patients, anaphylactoid reactions stopped when AN69 membrane was replaced by polysulfone membrane and ACE inhibitors were continued. In one case, reducing the dose of ACE inhibitors was sufficient to prevent new reactions. Anaphylactoid reactions did not occur in patients undergoing dialysis with another membrane (cellulosic or synthetic), nor in those on AN69 membrane without ACE inhibitor treatment. We conclude that back filtration of endotoxin-contaminated dialysate does not play the main role in the origin of such reactions, since they occurred in patients on hemofiltration with sterile and pyrogen-free substitution liquids. PMID- 1585933 TI - Prosthetic fistula survival and complications in hemodialysis patients: effects of diabetes and age. AB - Current trends in hemodialysis include increases in patient age, prevalence of diabetes, and use of high-efficiency dialysis. These patients often require prosthetic fistulas for vascular access. Little is known about fistula survival and complications in this setting. Hemodialysis patients at our center receiving new prosthetic fistulas between January 1, 1988 and January 1, 1991 were studied. Sixty-five prosthetic fistulas were placed in 50 nondiabetic and 73 in 51 diabetic patients. There were no differences in age, sex, race, or access type or location in patients with or without diabetes. Seventeen percent of fistulas were lost in nondiabetic compared with 32% diabetic patients (P less than 0.05). Life table analysis showed 1- and 2-year graft survivals of 88% and 77% in nondiabetic patients and 70% and 67% in diabetic patients. A significant difference in graft survivals was found for the time interval from 100 to 600 days after fistula placement. There were 188 complications in 92 of the grafts. There was no difference in the distribution of thromboses, elevated recirculations, or infections causing the first complication in patients with or without diabetes, but complications occurred earlier in diabetic patients (175 +/- 26 v 286 +/- 36 days, P less than 0.01). Nondiabetic patients with prosthetic fistula complications were significantly older than those without complications (64 +/- 4 and 56 +/- 2 years, respectively, P less than 0.05). No impact of age on complications was found in diabetic patients. The probability of a first thrombosis at 6 and 12 months was 29% and 49% in nondiabetic and 55% and 72% in diabetic patients (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585934 TI - Hypertension is not adequately controlled in hemodialysis patients. AB - To examine the adequacy of hypertension control, we monitored the blood pressure (BP) of 53 hemodialysis patients who received treatment for hypertension. BP measurement using an ambulatory BP monitor began 1 hour before dialysis and continued every 30 to 60 minutes for 48 hours until the next dialysis. Diet, medications including antihypertensive drugs, and hemodialysis prescription were not changed during this study. Each patient had a mean of 68 BP measurements during the monitoring period. Mean (+/- SD) systolic and diastolic BP levels of all patients over 48 hours were 158.6 +/- 22.7 mm Hg and 88.7 +/- 16.6 mm Hg, respectively, without diurnal variations. In these, BP loads (the percentage of systolic BP exceeding 150 mm Hg and diastolic BP exceeding 90 mm Hg) were 58.4% and 39.4%, respectively, suggesting that hypertension was inadequately controlled for more than half of the study period. Eight patients (15%) maintained BP within normal ranges at all times. All patients lost weight (2.9 +/- 0.9 kg) at the end of dialysis by ultrafiltration. However, only 27 patients (51%) had a greater than 5% decrease in mean arterial BP post-dialysis, which returned to predialysis levels within 12 to 24 hours. Reduction of BP postdialysis was significantly more common among black patients (72%) than white patients (30%) (P less than 0.01). However, there was no difference in age, cause of kidney disease, amount of ultrafiltration, and BP loads between those whose BP decreased and those whose did not. BP monitoring was repeated in eight patients, 2 to 3 months after adjustment of their antihypertensive regimens.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1585935 TI - Reduced risk of hypercalcemia for hemodialysis patients by administering calcitriol at night. AB - Renal osteodystrophy therapy in dialysis patients with calcitriol and intestinal phosphate binders containing calcium entails the risk of hypercalcemia. A study was performed using 35 hemodialysis patients to see whether the time of day when calcitriol is administered influences the incidence of hypercalcemia. It was shown that simply by administering at night (11:00 PM), the occurrence of hypercalcemia was significantly reduced. While greater than 80% of patients developed hypercalcemia when calcitriol was administered in the morning, when administered at night, this figure was only 50% (P less than 0.013). At the same time, the extent of hypercalcemia when calcitriol was administered at night was significantly lower than when it was administered in the morning. The incidence of hypercalcemia occurred regardless of the type of phosphate binder containing calcium used, whether it was calcium acetate or calcium carbonate. In addition, hypercalcemic episodes were always associated with hyperphosphatemia. On the basis of the above information, it would be expedient to administer calcitriol at night to dialysis patients, in order to reduce the risk of hypercalcemia and to preserve the hypophosphatemic effect of the applied intestinal phosphate binders. PMID- 1585936 TI - Intrafamilial phenotypic expression of autosomal dominant polycystic kidney disease. AB - It has been suggested that the clinical expression of autosomal dominant polycystic kidney disease (ADPKD) is uniform among individuals of a given family. To test this hypothesis, intrafamilial variations in ages at onset of first symptoms, types of first symptoms, serum creatinine concentrations, and renal sizes were evaluated in 131 patients with ADPKD from 36 unrelated families. These parameters were compared in younger and older affected relatives in the same family at a single time, due to difficulties of following them longitudinally. Because the natural course of the disease is to progress with age, it was presumed that disease progression in a given family was nonuniform if older individuals had lower serum creatinine concentrations, and/or smaller kidneys than their affected younger relatives, or if relatives of similar ages had different serum creatinine concentrations and/or kidney sizes. Nonuniform progression was suggested in 38% of affected relatives by serum creatinine concentrations and in 53% by kidney sizes. Ages at onset of first symptoms and types of first symptoms were also different in patients from the same families. These data indicate that phenotypic expression of ADPKD may differ considerably among patients who belong to the same families. PMID- 1585937 TI - Lupus nephritis: prognostic factors and probability of maintaining life supporting renal function 10 years after the diagnosis. Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL). AB - Data from 659 patients with a diagnosis of lupus nephritis were retrospectively collected among 32 nephrology centers in Italy, as a result of the collaborative effort of the Gruppo Italiano per lo Studio della Nefrite Lupica (GISNEL, Italian Lupus Nephritis Study Group). The overall probability of renal survival was 80% 10 years after the diagnosis. The probability of maintaining life-supporting renal function was evaluated according to several variables (clinical characteristics at presentation, World Health Organization [WHO] histologic classification). The presence at the time of diagnosis of hypertension and diffuse proliferative nephritis (WHO class IV) was associated with a worse prognosis. PMID- 1585938 TI - Glomerular capsular herniation in focal glomerular sclerosis. AB - Renal biopsy from a patient with focal segmental sclerosing glomerulopathy (FSSG) and nephrotic syndrome showed localized rupture of Bowman's capsule with herniation of a glomerular loop into the adjacent periglomerular connective tissue. Another glomerulus contained similar changes. Glomerular capsular herniation may be frequent, but unrecognized, in FSSG and would explain many of the morphological features seen in both primary and secondary forms. PMID- 1585939 TI - The use of nuclear magnetic resonance imaging in monitoring total body iron in hemodialysis patients with hemosiderosis treated with erythropoietin and phlebotomy. AB - Two hemodialysis patients with hemosiderosis were treated with combined erythropoietin and repeated phlebotomy. Serial nuclear magnetic resonance (NMR) imaging and serum ferritin levels were used to monitor the efficacy of treatment. This treatment modality has definite advantages over chronic deferoxamine therapy. NMR image-derived parameters offer an objective, accurate, and noninvasive indication of tissue iron stores. PMID- 1585941 TI - Liver disease after renal transplantation. PMID- 1585940 TI - Successful renal transplantation in a patient with systemic sarcoidosis and renal failure due to focal glomerulosclerosis. AB - In 1987, a patient presented with pulmonary sarcoidosis and progressive renal failure. Percutaneous renal biopsy showed focal glomerular sclerosis (FGS). Over the subsequent 4-year period, her renal failure progressed to require hemodialysis. During this time, her pulmonary sarcoidosis was treated with daily corticosteroid therapy and she remained in clinical remission. The patient received a one-haplotype-identical living-related renal transplant from her mother. The patient is now 25 months posttransplant with a serum creatinine of 106 mumol/L (1.2 mg/dL). Her sarcoidosis continues to be in clinical remission. In this report, we review the rare association of a primary glomerular lesion causing renal failure in patients with sarcoidosis. In addition, we detail the first successful renal transplant in such a patient. PMID- 1585942 TI - T-cell alveolitis in lung lavage of asbestos-exposed subjects. AB - In sarcoidosis and idiopathic pulmonary fibrosis, it has been reported that lymphocyte proportions in lung lavage predict the subsequent clinical course. Recent evidence has suggested that lymphocytes are important in the alveolitis of asbestosis. We hypothesized that a greater relative proportion of T-lymphocytes in lung lavage of asbestos-exposed subjects is associated with immune activation and may predict the subsequent clinical course. We assessed lymphocyte subsets in lung lavage and peripheral blood (PB) of 97 asbestos-exposed subjects and 10 unexposed normal, using flow cytometry analysis of monoclonal antibody-treated cells. T-cell alveolitis was defined as follows: [%lymphocytes in lavage x %CD3 in lavage] greater than 2 SD above that product in normals. Eighteen subjects had T-cell alveolitis (group 1) and 79 did not (group 2). There were no significant differences between the groups in age, smoking status, duration of exposure, lung function results, or frequency of plaques or profusion greater than or equal to 1/0. Percent CD2 was higher in lavage of group 1 compared with group 2. There was a trend for higher %Ia in lavage of group 1 compared with group 2. These results identify a subgroup of asbestos-exposed subjects with T-cell alveolitis but no present excess of asbestos-related disease who may be at risk for future asbestos related disease. PMID- 1585943 TI - A follow-up study of agricultural chemical production workers. AB - This retrospective follow-up study evaluated the mortality experience of 4,323 men employed at a plant in Alabama (AL) that manufactures agricultural and other chemicals. On average, there were 18 years of follow-up per subject during the study period of 1951 to 1987. The observed numbers of deaths among cohort members were compared with the numbers expected on the basis of United States (US) and AL general population mortality rates. The all causes standardized mortality ratio (SMR), computed using US rates as the referent, was 97 (233 observed/240 expected deaths) for whites and 68 (47/69) for blacks. White subjects had more than expected deaths from buccal cavity and pharynx (BCP) cancer [SMR = 388; 95% confidence interval (CI) = 125-905] and from esophageal cancer (SMR = 417; 112 1,067). Their lung cancer mortality rate was 50% higher than the rate of US white men and 14% higher than the rate of AL white men. Each of these three cancers has strong nonoccupational determinants, the roles of which were not assessed and which may have been responsible in whole or in part for the observed increases. The excesses of lung and esophageal cancer were concentrated among short-term employees, an observation which also argues against a causal link with occupational factors. Black men experienced no increased mortality from BCP, esophageal or lung cancer, but results for blacks were imprecise. For white and black subjects combined, there were 3 observed versus 0.62 expected deaths due to soft tissue sarcoma (p = 0.05). The job histories of subjects with this type of cancer did not suggest any shared occupational exposure. PMID- 1585944 TI - Recommendations for the investigation of abnormal hepatic function in asymptomatic workers. AB - Occupational medicine programs use medical surveillance tests to measure physiologic parameters that may be affected by workplace exposures. Surveillance tests can detect early detrimental changes before workers manifest recognizable symptoms. Hepatic function testing is one type of surveillance test used to monitor workers exposed to hepatotoxins. However, a significant proportion of these test reports return showing abnormal hepatic function without a readily apparent etiology. Follow-up investigation of abnormal liver enzyme tests is a commonly encountered problem in occupational medicine clinics. The algorithm proposed in this paper will outline a systematic approach for investigating abnormal hepatic function tests from asymptomatic workers. PMID- 1585945 TI - Hospital records as a data source for occupational disease surveillance: a feasibility study. AB - To assess the feasibility of using hospital records for occupational disease surveillance and to evaluate the quality of the industry/occupation (I/O) information available in these records, the computer file of all discharge diagnoses from a large health maintenance organization during 1985 was reviewed. The frequencies of discharge diagnoses previously listed as Sentinel Health Events (Occupational), or SHE (O), were calculated and three possible SHE(O) diagnoses--lung cancer, bladder cancer, and toxic hepatitis--were selected for further review. Outpatient charts of patients discharged for each diagnosis were abstracted with regard to I/O information and the discharged patients were interviewed by telephone to obtain a lifetime occupational history. The accuracy of the I/O information obtained from the hospital chart was compared to that obtained by patient interview by number of digits matched on standard classification codes. The frequencies of matches for occupation and industry were greater for "usual" than for "last" categories with both cancer diagnoses, but were similar for "usual" and "last" categories with toxic hepatitis. To assess the proportion of each possible SHE(O) diagnosis that was related to workplace exposures, the I/O information obtained by interview was rated in a blinded fashion by an experienced occupational medicine physician. The highest probability ratings for work-relatedness were noted for lung cancer, primarily due to asbestos exposure. The results of this study suggest that hospital records can be used to identify possible SHE(O); if adequate I/O information is available, then work-relatedness can be assessed. However, the accuracy of I/O obtained from hospital charts is relatively low. The efficient and accurate collection of I/O information from hospital records will require the use of a simple, easily coded instrument to be routinely administered on admission. PMID- 1585946 TI - Blood superoxide dismutase and plasma malondialdehyde among workers exposed to asbestos. AB - Blood superoxide dismutase (SOD) and plasma malondialdehyde (MDA) (an indicator of lipid peroxidation [LPO]) were determined in 97 randomly selected asbestos exposed workers (age range: 25-60 years, mean duration of exposures 19.8 +/- 8.3 years) and in 42 healthy male controls. MDA, SOD, and MDA/SOD ratio in asbestos exposed workers were significantly higher than in controls. Among both the controls and exposed workers neither age nor smoking was related to SOD or MDA levels. SOD was significantly positively correlated with MDA among the exposed workers. Such correlation was not observed among the controls. SOD but not MDA was significantly positively correlated with the duration of exposure to asbestos. Mean levels of SOD or MDA in exposed workers with radiographic signs of lung fibrosis or pleural thickening did not differ significantly from those without such signs. The results confirm the possible involvement of LPO and development of anti-oxidant mechanism(s) of prolonged exposure to asbestos in humans. However, SOD seems not to be the essential anti-asbestos-induced LPO. Relation between these factors and lung fibrosis is still unclear. PMID- 1585947 TI - Hard metal interstitial pulmonary disease associated with a form of welding in a metal parts coating plant. AB - We describe two cases of hard metal pulmonary disease (one fatal) in workers employed in the same area of a metal coating plant using the detonation gun process for applying a durable metal surface to metal parts. In this form of welding, a mixture of powdered metals, including tungsten carbide and cobalt, is heated by ignition of a flammable gas and propelled from the end of the "gun" at high temperature and velocity to form a welded metal coating. This process is done in an enclosed chamber and with each application, large volumes of fine aerosols are created. Inhalation exposure to hard metal may occur during the mounting and removal of the metal parts between applications, in spite of engineering controls and industrial hygiene surveillance. One of the cases presented with minimal chest x-ray abnormalities and an obstructive pattern on pulmonary function testing, although subsequent open lung biopsy showed diffuse interstitial pulmonary fibrosis. The fact that two cases of hard metal pulmonary interstitial disease occurred where thorough exposure control procedures and a surveillance program for cobalt were in place may indicate the need for revisions of the current technology used when hard metal is applied in the detonation gun process. PMID- 1585948 TI - Recognizing acute health effects of substitute fungicides: are first-aid reports effective? AB - Recently, many British Columbia sawmills stopped using traditional chlorophenate anti-sapstain fungicides and substituted 2-(thiocyanomethylthio) benzothiazole (TCMTB) and copper-8-quinolinolate (Copper 8). We conducted a cross-sectional study with two aims: to ascertain which acute health effects, if any, were associated with the use of the substitute fungicides; and to determine the effectiveness of first-aid records as a means of detecting acute health outcomes. Workers in five coastal sawmills were asked to complete a self-administered questionnaire about symptoms considered potentially related and unrelated to fungicide exposure, and about injuries commonly reported in sawmills. In addition, we collected first-aid records from the mills, and asked senior workers to estimate the duration of exposure to fungicides for each job. Symptoms found to be consistently elevated in TCMTB mills included dry skin around the eyes, blood-stained mucus from the nose, nose bleed, peeling skin, burning or itching skin, and skin redness or rash. No symptoms were consistently elevated in the Copper 8 mills. Symptoms related to TCMTB exposure were recorded only 12 times in first-aid logs during the study period (versus 335 questionnaire self-reports). This low symptom-recording frequency may be a function of established patterns of first-aid use in which illness symptoms are reported less frequently than injuries. PMID- 1585949 TI - The role of threshold limit values in U.S. air pollution policy. AB - This paper analyzes the role of threshold limit values (TLVs) in national air pollution policy during the 1980s, a period in which the Environmental Protection Agency (EPA) sought to delegate to individual states the authority to evaluate and regulate airborne toxic substances. We focus on 20 carcinogens and 11 substances with non-genotoxic health effects that were regulated by local air toxics programs using TLVs. Data from EPA's National Air Toxics Information Clearinghouse indicate that maximum TLV-based Ambient Air Level guidelines (AALs) frequently exceed minimum TLV-based AALs by a factor of greater than 1,000. Cancer potency data from EPA's Integrated Risk Information System suggest significant risks remain at TLV-based AALs. Cancer risks at the median TLV-based AAL exceed 1,000 cases per million exposed persons for cadmium (1,040), nickel and its compounds (1,420), propylene oxide (1,550), coke oven emissions (1,860), benzene (2,500), arsenic and its compounds (7,300), N-nitrosodimethylamine (21,000), asbestos (21,500), and ethylene dibromide (55,000). We also summarize published studies that report non-genotoxic health effects in workers exposed at levels near the TLV for 11 substances whose AALs were based on TLVs. Contrary to the assumption frequently made by state air toxics program, TLVs cannot be taken to represent no observed effect levels (NOELs) for regulatory purposes. PMID- 1585950 TI - Occupational hazards and pregnancy outcomes. AB - This study examined the association between exposure to occupational hazards and pregnancy outcomes using data from a case-control study conducted in 29 hospitals in Shanghai, China. The sample included 1,875 perinatal deaths and newborns with birth defects and the same number of controls. Information on mother's exposure to occupational radiation, chemicals, noise, and pesticides was investigated. Logistic regression analysis controlling for potential confounders showed that exposure to radiation before/during pregnancy was associated with antepartum fetal death, birth defects, small-for-gestational-age (SGA), and threatened abortion. Exposure to chemicals before/during pregnancy was associated with antepartum fetal death, early neonatal death, birth defects, preterm birth, and threatened abortion. Women exposed to pesticides during pregnancy had an increased risk of SGA and threatened abortion. Exposure to occupational noise during pregnancy increased the risk of antepartum fetal death. Furthermore, higher than expected numbers of congenital anomalies in the central nervous system (CNS) were identified among women exposed to chemicals before pregnancy and to pesticides during the first trimester of pregnancy. No significant association was found between occupational exposure and intrapartum fetal death. Although recall bias may be possible in our study, the findings encourage further research. PMID- 1585951 TI - The impact of anticipation of job loss on psychological distress and worksite blood pressure. AB - The impact of occupational stressful life events on psychological distress and blood pressure was examined among employees of a major New York City brokerage firm undergoing massive layoffs. One hundred thirty-nine employees of the firm, who had participated in a blood pressure screening in 1986, were rescreened during the period of layoffs within their company in 1989. About two-thirds of the 139 employees reported being "somewhat" or "very" anxious or upset in 1989 during the period of layoffs, and psychological distress was significantly elevated among those employees reporting possible or definite layoff or job change and/or difficulty in obtaining a comparable job. However, we found no increase in overall blood pressure level, and no effect of anticipation of job loss on 1989 blood pressure when controlling for 1986 blood pressure level, age, body mass index, work hours, and other demographic variables. On the other hand, employment in a department sold to another employer on the day of screening, as well as employment in a clerical job title, were both associated with significant increases in diastolic blood pressure of about 5 mm Hg. PMID- 1585952 TI - Immunological status and respiratory findings in furriers. AB - We studied 42 women occupationally exposed in the fur manufacturing industry (mean age: 34 years, mean duration of exposure: 11 years). The highest prevalence of positive immediate skin reactions to antigen of animal hair was found for marten (10%), followed by fox and lamb (7%), mink (5%), and Chinese lamb, domestic fox, and Chinese calf (2%). Precipitating antibodies were demonstrated for lamb (17%), astrakhan (14%), mink, domestic fox and skunk (12%), Chinese lamb (10%), and Chinese calf (7%). Increased total IgE was found in 9.5% of subjects. Chronic symptoms were consistently more prevalent among workers with positive skin tests and positive precipitins than among workers with negative tests. A high prevalence of acute symptoms during the work shift was found among furriers. The prevalence of these symptoms was higher among workers with positive precipitating antibodies than among those with negative studies but not for workers with positive skin tests. Mean acute reductions in ventilatory capacity over the work shift were recorded for most ventilatory parameters. In general, greater drops in respiratory parameters occurred in individuals with positive precipitins (e.g., FEV1: -6.5% vs. -2.8%; positive vs. negative precipitins) but not in those with positive skin tests. Our study suggests that workers in the fur manufacturing industry develop acute and chronic respiratory problems often associated with specific indicators of atopy. PMID- 1585953 TI - Thomas Bevill Peacock, pioneer occupational and environmental physician. PMID- 1585954 TI - Merchant Marine is not such a strange place for asbestos exposure. PMID- 1585955 TI - Community health, community risks, community action. PMID- 1585956 TI - Managed care for the seriously mentally ill. PMID- 1585957 TI - Use of community-based mental health programs by HMOs: evidence from a Medicaid demonstration. AB - BACKGROUND: Proposals to enroll Medicaid beneficiaries in health maintenance organizations (HMOs) have raised concerns that community-based mental health treatment programs would be adversely affected. METHODS: In Hennepin County (Minnesota) 35% of Medicaid beneficiaries were randomly assigned to prepaid plans. Random samples of individuals with severe mental illness with selected from the prepaid enrollees and from beneficiaries remaining with traditional Medicaid. The two groups were compared with respect to their use of community treatment programs and the write-off (the proportion of patient charges for which payment was not received) experienced by those programs for members of the study sample. RESULTS: There was no strong evidence that Medicaid beneficiaries with severe mental illness who were randomly assigned to prepaid plans used community based mental health treatment programs differently than did other Medicaid beneficiaries. However, write-offs were consistently higher for enrollees in prepaid plans. CONCLUSIONS: In the short run, the use of community-based mental health treatment programs need not be affected by enrollment of Medicaid beneficiaries in prepaid plans, providing that Medicaid program administrators take steps to minimize the disruption of ongoing treatment, offer beneficiaries a choice among prepaid plans, and encourage community treatment programs to contract with plans to serve beneficiaries. PMID- 1585958 TI - Commentary: caring for the indigent mentally ill--new strategies and old problems. AB - Christianson and his colleagues examine how Medicaid beneficiaries receive mental health services in HMOs by analyzing two important aspects of service delivery: the use of community-based treatment programs by Medicaid beneficiaries enrolled in health maintenance organizations (HMOs) and the reimbursement levels paid to these programs by HMOs. The hypotheses studied are complex issues that concern mental-health advocates and providers. Traditional community-based mental health services have always struggled to maintain their presence in the health care field, having to contend with changing funding priorities and more serious and multiple problems presented by their patients. For prepaid plans to work effectively for the indigent mentally ill, the complex issues have to be made clear and acknowledged as meaningful variables. PMID- 1585959 TI - Weight gain prevention and smoking cessation: cautionary findings. AB - OBJECTIVES: Weight gain is a consistent sequela of smoking cessation. A successful intervention might attract smokers who fear weight gain. If the gain causes smoking relapse, such an intervention might reduce smoking relapse risk. METHODS: Using a sample of 158 smokers who completed a 2-week smoking treatment program, we compared an innovative weight gain prevention intervention with both a nonspecific treatment and standard treatment. Subjects were assessed on weight and smoking behavior and followed for 1 year. RESULTS: A disturbing, unexpected finding was that subjects in both the innovative and nonspecific conditions had a higher risk of smoking relapse than did standard treatment subjects. Some differences were observed between abstinent and smoking subjects in weight gain by treatment condition. CONCLUSIONS: Both active interventions may have been so complicated that they detracted from nonsmoking. Also, caloric restriction may increase the reinforcing value of nicotine, a psychoactive drug, thereby increasing smoking relapse risk. The magnitude of weight gain after smoking cessation may not merit interventions that increase smoking risk. Perhaps attitudinal modifications are the most appropriate. PMID- 1585960 TI - Food sources, dietary behavior, and the saturated fat intake of Latino children. AB - BACKGROUND: Recent recommendations for Americans aged 2 and older call for a reduction in the average saturated fat intake to less than 10% of calories. METHODS: Using 24-hour dietary recalls collected from mothers of 4- to 7-year-old urban Latino children, we identified foods and dietary behavior patterns that distinguish children with higher and lower mean daily percentages of calories from saturated fat. RESULTS: Compared with children in the lowest quintile of intake, children in the highest quintile consumed more than twice as much saturated fat per day from high-fat milk products (18.5 g vs 7.8 g), mostly from whole milk. They did not consume different kinds of milk or different amounts of milk per eating occasion, but on average they consumed milk more frequently (2.8 vs 1.6 eating occasions per day). Even children in the lowest quintile, on average, exceeded the 10% of calories from saturated fat currently recommended. If low-fat (1% fat) milk had been substituted without other dietary changes, all but the highest two quintiles would have been within the recommended level. CONCLUSIONS: The substitution of low-fat for whole milk appears to be a key strategy for preschool children for achieving recommended levels of saturated fat intake. PMID- 1585961 TI - Socioeconomic status and health: how education, income, and occupation contribute to risk factors for cardiovascular disease. AB - BACKGROUND: Socioeconomic status (SES) is usually measured by determining education, income, occupation, or a composite of these dimensions. Although education is the most commonly used measure of SES in epidemiological studies, no investigators in the United States have conducted an empirical analysis quantifying the relative impact of each separate dimension of SES on risk factors for disease. METHODS: Using data on 2380 participants from the Stanford Five-City Project (85% White, non-Hispanic), we examined the independent contribution of education, income, and occupation to a set of cardiovascular disease risk factors (cigarette smoking, systolic and diastolic blood pressure, and total and high density lipoprotein cholesterol). RESULTS: The relationship between these SES measures and risk factors was strongest and most consistent for education, showing higher risk associated with lower levels of education. Using a forward selection model that allowed for inclusion of all three SES measures after adjustment for age and time of survey, education was the only measure that was significantly associated with the risk factors (P less than .05). CONCLUSION: If economics or time dictate that a single parameter of SES be chosen and if the research hypothesis does not dictate otherwise, higher education may be the best SES predictor of good health. PMID- 1585962 TI - Socioeconomic and behavioral correlates of body mass index in black adults: the Pitt County Study. AB - BACKGROUND: Obesity is more prevalent among Black women than Black men, but there is little information on the correlates of obesity in Blacks. This study describes the relations of sociodemographic factors and health behaviors to body mass index in a southern, Black population. METHODS: In 1988, a community probability sample of 1784 Black adults, aged 25 to 50, was examined in Pitt County, NC. RESULTS: More women than men were at least 20% overweight (57% vs 36%). The relation of socioeconomic status (a composite of education and occupation) to age-adjusted body mass index level was inverse in women but not in men. Body mass index did not differ with either current energy intake or energy expenditure. Smokers and drinkers had lower age-adjusted levels than non-smokers and abstainers. CONCLUSIONS: Since the excess body mass index levels associated with low socioeconomic status in women could not be explained after controlling for adverse health behaviors, further epidemiologic study of risk factors for obesity in Black women is recommended. PMID- 1585964 TI - The second Chicago televised smoking cessation program: a 24-month follow-up. AB - OBJECTIVES: As smoking decreases in the population, the remaining smoking population will change, and cessation initiatives will have to incorporate strategies designed for these smokers. METHODS: To study patterns of response to a cessation intervention composed of 20 televised segments and the American Lung Association Freedom from Smoking in 20 Days manual, this study compared cessation rates over 24 months in a cohort of smokers who registered for a cessation program with those in a cohort selected from the smoking population at large. RESULTS: At post intervention, multiple point prevalence of cessation among participants, adjusted for baseline smoking, was 14% among registrants and 6% in the population; at 24 months the adjusted rates were 6% and 2%, respectively. Heavy smokers benefited more than light smokers, and there was a consistent dose response relationship between extent of exposure to the intervention and cessation. CONCLUSION: The effects of the intervention were strongest for those who read the manual and watched the programs daily. Manual use was important, and those who did not read it did not appear to benefit. Compared to the population and given full participation, heavy smokers benefited more than lighter smokers. PMID- 1585963 TI - Prevention of cigarette smoking through mass media intervention and school programs. AB - OBJECTIVES: In this study we tested the ability of mass media interventions to enhance the efficacy of school cigarette smoking prevention programs. METHODS: For 4 years, students in one pair of communities received media interventions and school programs that had common educational objectives. Students in a matched pair of communities received only the school programs. The combined cohort of 5458 students was surveyed at baseline in grades 4, 5, and 6 and was followed up annually for 4 years. RESULTS: Significant reductions in reported smoking, along with consistent effects on targeted mediating variables, were observed for the media-and-school group. For cigarettes per week the reduction was 41% (2.6 vs 4.4); for smoking cigarettes yesterday the reduction was 34% (8.6% vs 13.1%); and for smoking in the past week the reduction was 35% (12.8% vs 19.8%). No effects were observed for substance use behaviors not targeted by the interventions. CONCLUSIONS: These results provide evidence that mass media interventions are effective in preventing cigarette smoking when they are carefully targeted at high-risk youths and share educational objectives with school programs. PMID- 1585966 TI - First-year impact of the 1989 California cigarette tax increase on cigarette consumption. AB - We employed a time series design to evaluate the impact of the 1989 California cigarette tax increase on cigarette consumption in California. Adult per capita consumption data from 1980 to 1990 were analyzed for California and the United States. Trend data indicated a sharp drop in California cigarette consumption coincident with the tax increase. Time-series regression analyses support this observation, and suggest that a 5% to 7% decline in consumption is attributable to the tax increase. PMID- 1585965 TI - Do time trends in food supply levels of macronutrients reflect survey estimates of macronutrient intake? AB - BACKGROUND: Two types of data may be used to estimate trends in food and nutrient intake by the US population: per capita food supply estimates and survey estimates of individual intake. Because these data vary markedly in measurement goals and methods, we examined whether trends in food supply and survey intake estimates for fat, carbohydrate, and protein are reflective of one another. METHODS: The data selected for comparison included all available survey estimates of mean intake by the US population (i.e., periodic estimates from 1965 to 1988) and all available per capita food supply estimates from a comparable time period (i.e., annual estimates from 1965 to 1985). RESULTS: The two types of data generally did not reflect the same trends. Furthermore, expressing macronutrient levels as percentage of calories rather than in grams affected the trend relationships. CONCLUSIONS: Our findings indicate that caution is needed in the selection and application of available data to estimate trends in macronutrient intake by the US population and in the interpretation of these data with regard to public health research, policies, and programs. PMID- 1585967 TI - Drug use and suicide ideation and behavior among North Carolina public school students. AB - We used data from 3064 respondents to the 1990 North Carolina Youth Risk Behavior Survey to examine the relationship between adolescent drug use and suicide ideation and behavior. Principal components analysis followed by varimax rotation was performed separately on the drug use and suicide items. Correlation coefficients computed between the two sets of factor scores and comparison of mean drug use factor scores revealed that drug use, particularly of crack/cocaine, was related to increased suicide ideation and behavior. PMID- 1585968 TI - Delay in ambulance dispatch to road accidents. AB - When a road accident occurs, the police communications officer, or 911 operator, generally receives the first call. If the caller reports injuries, the emergency medical services dispatcher is notified immediately; but if the caller is uncertain of injuries, the operator may wait. Most often an ambulance is not needed. However, in nearly 20% of fatal road accidents in Missouri, waiting for confirmation of need resulted in a delay of 5 minutes or more in the dispatch of an ambulance. PMID- 1585969 TI - Race, belief in destiny, and seat belt usage: a pilot study. AB - A survey of 1063 individuals found that when belief in destiny was statistically controlled, differences in seat belt use by race disappeared. Thus, racial differences in seat belt use are statistically accounted for and might be explained by belief in destiny. Efforts to increase seat belt use should target minority groups rather than include them in broadbrush programs. Further, these efforts should take into account this important difference in motivation. PMID- 1585972 TI - Falls among the elderly: a community prevention program. PMID- 1585970 TI - A neonatal hepatitis B surveillance and vaccination program: New York City, 1987 to 1988. AB - From July 1987 to June 1988, 1030 pregnant women with hepatitis B were reported to a New York City surveillance program. Among 832 infants under follow-up, the coverage rates for combined hepatitis B immune globulin and vaccine doses 1, 2, and 3 were 84%, 77%, and 59%, respectively. Infants covered by Medicaid and uninsured Black and Hispanic infants were significantly less likely to be completely vaccinated. An estimated 160 cases of chronic hepatitis B infection were prevented among infants enrolled in the program. Strategies are needed to improve vaccine coverage among hard-to-reach groups. PMID- 1585971 TI - Physician and infection control practitioner HIV/AIDS reporting characteristics. AB - We surveyed a random sample of South Carolina physicians and infection control practitioners about the reporting of human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) cases. Of physicians surveyed, 79% indicated that HIV infection as well as AIDS should be reported by name. The following characteristics were associated with those physicians who do not report AIDS cases: not feeling responsible for reporting, not reporting a case perceived to have been reported in another state, believing that information required for reporting is not on the chart, and residing in an urban setting. Targeted education can address these underreporting factors. PMID- 1585973 TI - Community-based case management of HIV disease. PMID- 1585975 TI - Use of odds ratio questioned. PMID- 1585974 TI - Risk of exposure to outdoor advertising of cigarettes and alcohol. PMID- 1585976 TI - Plague surveillance in Los Angeles County. PMID- 1585977 TI - Epidemiologic studies on electromagnetic fields and cancer. PMID- 1585978 TI - The correct use of growth charts. PMID- 1585979 TI - Are we really no. 1? PMID- 1585980 TI - Rhytidectomy: technique and complications. PMID- 1585981 TI - Reconstruction of small- and medium-sized defects of the lower lip. AB - Defects of up to one third of the lower lip can usually be closed primarily, using one of the excision shapes described above. Defects of 30% to 50% of the lower lip can be closed with a stair-step or lip-switch flap. In most circumstances, stair-step reconstruction attains good function more quickly than the lip switch flap and has a better aesthetic result. Defects of 50% to 75% of the lower lip can be closed with a fan flap or a Karapandzic flap; the Karapandzic flap generally provides a better functional result. Both of these flaps cause rounding of the corner of the mouth that compromise the aesthetic result. PMID- 1585982 TI - Contemporary aspects of diagnostic audiology. PMID- 1585983 TI - The risk of contralateral lymphatic metastases for cancers of the larynx and pharynx. AB - PURPOSE: This study was undertaken to determine the risk of cervical metastases to the contralateral side in patients treated for carcinoma of the larynx and pharynx. PATIENTS AND METHOD: Retrospective evaluation of 846 patients treated between 1962 and 1981 with carcinoma of the supraglottis, transglottis, and pyriform sinus were reviewed. Lesions were classified as either transglottic with fixed vocal cord (TG-F), transglottic with mobile vocal cords (TG-M), central supraglottic (SG-C), marginal supraglottic (SG-M), glossoepiglottic cancers of the suprahyoid epiglottic, vallecula, and tongue base (SG-GE), and cancers of the pyriform sinus (PS). RESULTS: Contralateral lymph node metastases were identified at presentation or later developed in SG-GE 26%, SG-M 14%, PS 13%, SG-C 7%, TG 4%. Contralateral metastases were significantly higher in patients with ipsilateral metastasis. The risk of contralateral metastasis was unrelated to the primary tumor size. CONCLUSIONS: All but 79 patients received variable doses of irradiation to the contralateral neck. Therefore, the risk of metastatic disease is probably higher than reported. Parotid-sparing radiation technique is suggested for centrally located cancers of the supraglottis and transglottis when ipsilateral nodes are not involved because the risk of contralateral neck involvement is sufficiently low that opposite neck irradiation may be safely avoided. PMID- 1585984 TI - Synchronizing videostroboscopic images of human laryngeal vibration with physiological signals. AB - PURPOSE: This report describes a new system that permits the precise correlation of videostroboscopic images with corresponding physiological measures, such as glottography and subglottic pressure. METHOD: A healthy volunteer had unilateral vocal cord paralysis induced by infiltrating local anesthesia into the recurrent and superior laryngeal nerve. Vocal-fold vibrations were monitored by photoglottography (PGG) and electroglottography (EGG). Analog signals from the EGG and PGG were synchronized with the video and correlated. RESULTS: The method described permits images to be sampled throughout sustained phonation. This technique allows study of events during glottic vibration. Results obtained have been in close agreement with previous studies that correlate the vocal-fold morphology to glottographic signal using other methods. This technique is inexpensive in comparison with high-speed filming. The main disadvantage of this method is related to the limitations of stroboscopy. PMID- 1585985 TI - Therapeutic alternatives in the treatment of life-threatening vasoformative tumors. PMID- 1585986 TI - Neomycin ototoxicity. PMID- 1585987 TI - Innervation of the canine cruciate ligaments. A neurohistological study. AB - A search for mechanoreceptors within the substance of the cruciate ligaments was undertaken using the modified gold-chloride technique. Abundant Pacinian, Vater Pacini, Ruffini end organs and Ruffini-type receptors were found within the substance of the anterior and posterior cruciates. The receptors were innervated by axons of 5 to 10 micrometers in diameter penetrating from the synovium investing the ligaments. The findings support the contention that the cruciate ligaments have important mechanoreceptive and proprioceptive functions. PMID- 1585988 TI - Dorsal nerve root origins of the cutaneous nerves of the feline pelvic limb. AB - The dorsal root origins of cutaneous nerves supplying the feline pelvic limb were determined electrophysiologically in 11 cats. Cutaneous nerves were surgically exposed and the presence or absence of an evoked potential in response to stimulation of individual dorsal roots was noted. The dorsal cutaneous branches of L3-L5 and S3, and the lateral cutaneous branch of L3 each arose solely from their parent spinal nerves. The L7, S1, and S2 dorsal cutaneous branches had multiple dorsal root origins. The lateral cutaneous femoral nerve originated from L3-L6 dorsal roots in 4 patterns of origin, and the saphenous nerve originated from L4-L6 dorsal roots in 2 patterns of origin. The lateral and caudal cutaneous sural nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The lateral and medial plantar nerves arose from L6-S2 roots in 4 and 2 patterns, respectively. The superficial and deep peroneal nerves originated from L6-S1 roots in 2 and 3 patterns, respectively. The caudal cutaneous femoral nerve or its branches arose from L7-S3 in 8 origin patterns. The dorsal nerve of the penis and the superficial perineal nerve arose from L7-S3 and S1-S3 roots, respectively, each in 4 patterns. A subtle correlation between plexus type and dorsal root origins of the cutaneous nerves was noted. PMID- 1585989 TI - The humeroscapular bone of the great horned owl (Bubo virginianus) and other raptors. AB - A small, separate, bony density dorsal to the shoulder joint is radiographically visible in several species of large hawks and owls. Gross dissection and histological examination show the bone to lie on the deep surface of the major deltoid muscle in intimate association with the dorsal coracohumeral ligament of the shoulder joint. The tendon of the supracoracoideus muscle passes immediately cranial to the humeroscapular bone. Two ligaments distinct from the shoulder joint capsule attach the humeroscapular bone to the proximal humerus: one passes to the proximal edge of the pectoral crest of the humerus, and the other passes to the ventral tubercle of the humerus. The bone was described as the humeroscapular bone in reference to a similar fibrocartilaginous structure possessed by some birds. The humeroscapular bone is present in the great horned owl (Bubo virginianus), the screech owl (Otus asio), the barred owl (Strix varia), the red-tailed hawk (Buteo jamaicencis), the Cooper's hawk (Accipiter cooperii), and the sharp-shinned hawk (Accipiter striatus). The bone is absent in the barn owl (Tyto alba), the osprey (Pandion haliaetus), the golden eagle (Aquila chysaetos), and the turkey vulture (Cathartes aura), though some of these species possessed a similar fibrocartilaginous structure. Whether the humeroscapular structure develops as bone or cartilage in a given species may be related to other morphological features of the wing, and/or to characteristics of the predatory behavior of the species. Clinicians and anatomists dealing with birds of prey must be aware of the presence of the humeroscapular bone to avoid misinterpreting it as a fracture fragment. PMID- 1585990 TI - The apical ligaments of the penis of the goat and sheep. AB - The penile apical ligaments of 13 goats and 8 sheep were dissected and described. Unlike the single apical ligament of the bull penis, both goats and sheep had one ligament on each side of the apex of the penis with no apparent connection over the dorsal surface. These lateral apical ligaments consisted of substantial connective tissue fibers that arose from the outer layers of the tunica albuginea and varied from 6.0 to 10.0 cm in length. The left apical ligament was longer and thicker than the right. The left apical ligament of the sheep penis was divided into a dorsal and a ventral branch. Both the goat and sheep possessed flattened perivenous ligaments that originated from the apical fascia and extended caudally along each side of the dorsal vein of the penis. PMID- 1585991 TI - Retinal pigment epithelial fine structure in the red-tailed hawk (Buto jamaicensis). AB - As part of a comparative morphological study, the fine structure of the retinal epithelium (RPE), choriocapillaris and Bruch's membrane (complexus basalis) has been studied by electron microscopy in the red-tailed hawk (Buteo jamaicensis). In this species the RPE consists of a single layer of low cuboidal cells which display numerous basal (scleral) infoldings and extensive apical (vitreal) processes which interdigitate with photoreceptor outer segments. These epithelial cells are joined laterally by a series of basally located tight junctions. Internally SER is the most abundant cell organelle while only small amounts of RER are present. Polysomes are however abundant as are mitochondria. The RPE cell nucleus is large and vesicular. Melanosomes are mainly located in the apical processes of the RPE cells in light-adaptation. Myeloid bodies are large and numerous in light-adaptation and often show ribosomes on their outer border. Bruch's membrane (complexus basalis) shows the typical pentalaminate structure noted in most vertebrates but with only a poorly defined central elastic layer. The endothelium of the choriocapillaris is very thin facing the RPE but is only moderately fenestrated. The choriocapillaris in this species is unusual however in that many of the fenestrae show a double-layered diaphragm. PMID- 1585992 TI - Ultrasonographically detectable ring structure in avian (Gallus gallus) egg yolks. AB - After a preliminary finding of ultrasonographically detectable ring structure within the yolk of avian eggs, a study was initiated to investigate these properties. Ultrasonographically detectable alternating hyperechoic and hypoechoic rings within the egg yolk were found to be consistent but variability occurred in ring numbers, thickness, and clarity. Rings were best seen at two days post oviposition and were not affected by refrigeration or heating of the yolks. The usefulness of rings in experimental studies of yolk content of lipoprotein is postulated. PMID- 1585993 TI - [Is there an internal tongue musculature in parrots?]. AB - The result of this study shows that the tongue of the parrot has voluntary muscle that runs dorsally to the apex of the tongue. This musculature can be regarded as evidence that a reduced internal musculature exists. PMID- 1585994 TI - Ependyma of the goat. Part IV. Ependymal lining of the median eminence in goats under physiological and experimental conditions. AB - The sexual differentiation of the ME ependymal lining surface structure has been proved in goats. Suitable hormonal preparations applied to females during anestrus induced on the median eminence the same picture as that during estrus. Only after gonadectomy in both the females and males there were dense macrophages like SEC on the ME protruding from the deeper layers of the eminence. Their potential function is discussed. PMID- 1585995 TI - [Comparative studies of the hair of Pudu pudu and European red deer]. AB - The awn and the fur hair of Pudu were investigated. Values of the length are between 14 and 56 mm for the awn hair, and 9 to 36 mm for the fur hair. Hair thickness--especially at the thickest point--ranges from 140 to 236 microns for the awn hair and from 19 to 106 microns for the fur hair. The values of the cuticle scales are between 12 and 18 microns for the length and between 41 and 66 microns for the width. The shape of the scales is rectangular in the basal three quarters (R) and becomes crenated (R/Z) in the apical quarter. The medulla is continuous with large hollow vesicles. The similarity to the hair of european red deer is surprising. PMID- 1585996 TI - An ultrastructural study of the Sertoli cell in the water buffalo (Bubalus bubalis). AB - The ultrastructure of Sertoli cell in the water buffalo (Bubalus bubalis) was observed in a transmission electron microscope. The nucleus had homogeneous nucleoplasm, scarce heterochromatin and multivesicular nuclear body (MNB). The MNB was composed of numerous vesicles and ribosome-like dense structures. The vesicles varied in size and number and contained a sparse and flocculent substance. In the indentation of the nucleus, aggregates of ribosomes were frequently observed. In the apical and middle region of the cell, long mitochondria and microtubules were distributed parallel to the long axis of the cell. Non-laminated smooth ER and some ribosomes were also recognizable throughout this region. In the basal region, widely-distributed laminated smooth ER was characteristic. Microfilament bundles at ectoplasmic specialization were irregularly arranged. Frequently-emerged nodular processes occasionally separated from basal lamina and formed round structures within Sertoli cytoplasm. Although these characteristics of buffalo Sertoli cell were very similar to those of the bovine studied, the aggregate of ribosomes was more developed in the buffalo. PMID- 1585997 TI - Enhanced proliferation of undifferentiated spermatogonia after treatment of short photoperiod exposure in the Syrian hamster, Mesocricetus auratus. AB - Five Syrian hamsters were exposed to a short photoperiod (8L:16D) during 159 days. Atrophied testes were removed, fixed in Allen's solution; paraffin sections of the testicular tissues and whole-mounted seminiferous tubules were prepared. The numbers of various types of spermatogonia were investigated and compared with those in animals maintained in natural photoperiod (12L:12D). All the types of differentiated spermatogonia (A1, A2, In, B1, B2) were significantly decreased in number after the treatment of short photoperiod exposure, while undifferentiated spermatogonia (isolated, paired and aligned type) were significantly increased at stages V-VI and VII-VIII of the seminiferous epithelial cycle. This strictly local reaction of the undifferentiated spermatogonia to the loss of the differentiated spermatogonia suggests the presence of a feedback effect of a certain type(s) of differentiated cells to the undifferentiated spermatogonial proliferation. This feedback mechanism may also play an important role for regulating annual changes in spermatogenesis of seasonal breeders, not only in laboratory but also in natural habitat. PMID- 1585998 TI - Cell types in the main excretory duct of the submaxillary gland of the rat. AB - This work is an ultrastructural study of the cells of the excretory duct epithelium of the submaxillary gland of the rat. This epithelium undergoes progressive loss of cytoplasm which leads to the presence of three distinct types of cell. PMID- 1586000 TI - What characterizes allergic asthma? PMID- 1585999 TI - Immunocytochemical study of the ultimobranchial tubule in Wistar rats. AB - A systematic immunohistochemical study of the ultimobranchial tubule (UBT) has been carried out in 45 Wistar rats of different ages (0, 5, 10, 15, 20, 25, 30, 60 and 120 days). The existence of calcitonin immunoreactive cells in the UBT wall has been demonstrated in a 5-days old rat. In addition, immunohistochemical studies for thyroglobulin revealed positive staining in follicular cells connected to the UBT and, occasionally, in isolated cells lying within solid clusters from the UBT. These last results together with the continued and repeated existence of numerous mitosis and PAS (+) microfollicles, apparently rising from the UBT, support the hypothesis that the ultimobranchial body (UBB) may contribute partially to the formation of a part of the follicular component. PMID- 1586001 TI - Evolving epidemiology of HIV infection among adults. AB - Whereas new, or changes in existing, routes of transmission of HIV have not been identified in the 11 years since AIDS was identified as a clinical syndrome, changes in the epidemiology of HIV infection in the US have been identified during that period. The role of injection drug use as a risk for both parenteral and sexual transmission of HIV has increased substantially during this period. Heterosexual transmission is becoming more prominent as the epidemic continues to "mature" in the US. The likelihood that heterosexual transmission will become progressively more important in the spread of HIV in the US in the next several years seems high. The ability of individuals in some populations at risk for infection to modify risk behaviors has led to a reduction in transmission of HIV in those populations. The addition of nucleoside analog antiretrovirals and effective chemoprophylaxis for Pneumocystis carinii pneumonia has led to increases in both the quality and duration of life for some populations of HIV infected patients. Neither a chemotherapeutic cure nor a vaccine is on the immediate horizon; education and behavior modification remain the cornerstones of current prevention efforts. For a variety of complex reasons, inappropriate scrutiny has been focused on the remote risks of health-care provider-to-patient transmission of HIV. In the past 11 years medical science has made remarkable progress in understanding the etiology, biology, epidemiology, pathogenesis, and prevention of HIV infection. Despite this progress, a great deal of work remains to be done not only in the medical and basic science arenas but also in the behavioural and sociological sciences. PMID- 1586002 TI - Bronchiectasis in a 31-year-old woman. PMID- 1586003 TI - Utility of additional skin testing in "nonallergic" asthma. AB - It has been suggested that asthma almost always as an allergic basis. In this study we tried to determine whether an additional limited skin test panel would be useful in revealing hidden allergies in our "nonallergic" asthmatic patients. In 127 consecutive asthmatic adults, a survey panel of seven tests (rat, mouse, cockroach, Helminthosporium, Chaetomium, Pullularia, and Penicillium) was used in addition to our routine skin test panel (local pollens, Alternaria, Aspergillus, Hormodendrum, dog; and standardized cat, D. pteronyssinus, and D. farinae). On the basis of the routine test panel, 111 patients (87%) were allergic and 16 patients (13%) were nonallergic. Only one nonallergic patient (6%) had any positive survey test results (to cockroach only) while 69 allergic patients (62%) had at least one positive survey test result (p less than .00002). With the possible exception of cockroach, additional skin testing with our survey panel to search for hidden allergies in otherwise nonallergic asthmatic adults is not worthwhile. PMID- 1586004 TI - Sensitization to the storage mite Lepidoglyphus destructor in wheat flour respiratory allergy. AB - Occupational allergy due to hypersensitivity to cereal flours is relatively common among bakers and grain-store workers. Storage mites can contaminate wheat flour and could be an important cause of allergic symptoms due to inhalation. Forty-three patients with criteria for allergic sensitization to wheat flour (skin tests, specific IgE to wheat flour and positive challenge tests) were included in a study to investigate the prevalence of cosensitization to Lepidoglyphus destructor (Ld). This mite was the predominant species in the wheat flour samples supplied by our patients. We found that 30% of the patients had IgE mediated hypersensitivity of Ld. Of these, 23% did not have a relationship with any bakery or agriculture. We conclude that the prevalence of sensitization to Ld in patients sensitized to wheat flour is important. PMID- 1586005 TI - Effect of a whey hydrolysate prophylaxis of atopic disease. AB - The incidence of atopic manifestations was analyzed in infants "at risk" because of histories of atopy in first degree relatives. The incidence of atopic manifestations was significantly reduced (P = .0011) during the first 6 months of life when only the whey hydrolysate was administered (2/32 infants, 6.3%) compared with the incidence when an adapted formula was given (14/35 infants, 40%). This beneficial effect continued during the 6 to 12-month period, after diversification of the diet at 6 months. At the age of 1 year, 7/32 (21.8%) of the infants in the whey hydrolysate group had presented with manifestations of probable atopic disease compared with 17/35 (48.6%) infants in the adapted formula group (P = .021). The incidence of cow milk protein sensitivity was evaluated at 5/32 (15.6%) in the hydrolysate group and 15/35 (42.8%) in the adapted formula group (P = .014). Other foods such as egg and fish may be responsible for manifestations in three infants in hydrolysate group and in five infants of the adapted group (9.4% and 14.3%, respectively NS). These preliminary data show that the administration of a whey hydrolysate during the first 6 months of life to babies "at risk" decreased the incidence of atopic disease up to the age of 12 months. The incidence of cow milk protein sensitivity appeared to be decreased, whereas the incidence of sensitivities to other food proteins was comparable in both groups. PMID- 1586006 TI - Particulate air pollution and hospitalization for asthma. AB - Age-specific quarterly asthmatic hospital discharge rates in Hong Kong during 1983 to 1989 were examined in relation to mean levels of six pollutants: sulfur dioxide (SO2), ozone (O3), total suspended particles (TSP), respiratory suspended particles (RSP), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Discharges from the hospital of children under 14 years of age represented 56% of 33,952 discharges recorded in all age groups. Trends of adult hospitalization rates over time remained stable during the study period. In children, however, there was an increase in these rates, particularly marked in the age group of 1 to 4 years. Univariate analysis revealed a strong correlation between quarterly mean TSP and hospital discharge rate for the 1 to 4-year-old children (r = .62, P less than .001). In the 5 to 14-year-old age group, there was an inverse relationship between hospital discharge rate and sulfur dioxide level (r = -.38, P less than .05). Stepwise multiple regression analysis, controlling for confounding variables (seasonal and annual trends of asthma hospitalizations) confirmed these relationships. A highly significant linear regression equation was derived between hospitalization rate for ages 1 to 4 years and total suspended particles (P less than .001). The highly significant correlation between pollution and asthmatic hospitalization rate for the 1 to 4-year-old group suggests that young children are vulnerable to the adverse environmental effects of pollution. Auditing these relationships offers a logical basis for approaching control. PMID- 1586007 TI - Pollen-related allergy in Italy. AB - Pollen-related allergies are very common in Italy and pollinosis is the commonest allergic disease. The type of allergenic plants and the prevalence of hay fever varies among regions. In the Mediterranean area there are characteristic climatic conditions (mildness of winter, summer dryness) that facilitate the growth of a typical vegetation with its associated various types of allergenic pollen grains, some of them very different from those of central and northern Europe. Italy has a central position in the Mediterranean basin, but because of its geographic characteristics, there are different climatic aspects with different vegetation between northern, central, and southern areas. Gramineae are the most common allergenic plants in northern and central Italy, where more than 60% of patients with pollinosis are grass-pollen sensitive. Parietaria is the most important pollinating plant in southern Italy and Liguria. Olea europaea, the olive tree with cultivation widespread in the whole Mediterranean basin, is responsible for frequently severe pollinosis, particularly in some regions of the southern Italy. PMID- 1586008 TI - Abnormal responses of the autonomic nervous system in food-dependent exercise induced anaphylaxis. AB - We investigated abnormal responses of the autonomic nervous system and measured plasma histamine levels before and after exercise challenge following food ingestion in four patients with food-dependent exercise-induced anaphylaxis. The patients' histories and the radioallergosorbent tests showed that food-dependent exercise-induced anaphylaxis resulted from preexercise-ingestion of shrimp, hen's egg, and any food in two patients, one patient and one patient, respectively. The plasma histamine level increased in only one of four patients when the exercise challenge followed the ingestion of nonoffending foods. Our investigation of changes in the autonomic nervous system before and after food-exercise challenge in all patients included comparing results obtained after the food-exercise challenge in controls and comparing results obtained before food-exercise challenge in the patients. After food-exercise challenge, systolic blood pressure significantly decreased and the heart rate increased during the postural test, heart rate tended to decrease in the Aschner test, and the increase of systolic blood pressure was reduced in the cold pressor test. After food-exercise challenge, the parasympathetic nervous activity increased and responsiveness of the sympathetic nervous system was reduced. Food-dependent exercise-induced anaphylaxis may therefore occur in relation to allergic reactions and abnormality of the autonomic nervous system. PMID- 1586009 TI - Purification of the ninth component of the bovine complement cascade. AB - Conditions for purification of the ninth component of bovine complement (C9) were established. The conditions for binding and elution from diethylaminoethyl cellulose and hydroxylapatite were different than for human C9. Serum albumin, a frequent contaminant of bovine C9 preparations, was removed by chromatography on reactive-red agarose. The calculated molecular weight of bovine C9 was 66,000, and reduction with 2-mercaptoethanol affected its migration on polyacrylamide gel electrophoresis. Some preparations of bovine C9 migrated as 2 bands when partially reduced, but extensively reduced preparations had a single band. PMID- 1586010 TI - Safety and efficacy of an attenuated strain of Salmonella choleraesuis for vaccination of swine. AB - The purpose of this study was to determine the safety and efficacy of a live Salmonella choleraesuis immunizing strain, obtained by repeated ingestion and recovery through porcine neutrophils. The strain was tested in mice and in pigs. The vaccine was safe and effective in controlled experimental trials, using clinical, pathologic, and microbiologic criteria. Vaccinated pigs were able to maintain normal weight gains during the 4-week observation period following challenge inoculation with a high dose of a virulent strain. PMID- 1586011 TI - Prevalence of autoantibodies to thyroglobulin, thyroxine, or triiodothyronine and relationship of autoantibodies and serum concentrations of iodothyronines in dogs. AB - Assays were developed to detect and measure autoantibodies (AA) to thyroglobulin (Tg) and to the thyroid hormones, thyroxine (T4) and triiodothyronine (T3). An ELISA to detect AA to Tg was developed, using purified canine Tg as the antigen and goat anti-canine IgG conjugated with alkaline phosphatase as the second antibody. A highly charged agarose electrophoresis assay was used for determination of AA to T4 and T3. Sera from dogs (n = 119) with clinical signs consistent with hypothyroidism were tested for AA to Tg, T4, and T3. Autoantibodies to at least 1 of the 3 thyroid antigens were detected in 58 of the 119 (48.7%) sera tested. Autoantibodies to Tg were detected more frequently in samples with low serum concentrations of thyroid hormones than in samples with normal concentrations. The presence of AA to T4, T3, or both was not significantly associated with low thyroid hormone concentrations, but this lack of association may have been attributable to binding of AA in the measurement of thyroid hormones by radioimmunoassay. PMID- 1586012 TI - Evaluation of total protein content in tears of dogs by polyacrylamide gel disk electrophoresis. AB - Concentration of total proteins was measured and sodium dodecyl sulfate polyacrylamide gel disk electrophoresis was performed on tear and plasma samples obtained from 26 healthy dogs, and the results were compared. Mean +/- SEM concentration of total proteins in tears was 0.63 +/- 0.04 g/dl, and significant effects of age or gender were not found. The protein composition of tears in dogs was complex, and bands from light and heavy chains of immunoglobulins were identified by electrophoresis. PMID- 1586013 TI - Use of a direct enzyme-linked antiglobulin test for laboratory diagnosis of immune-mediated hemolytic anemia in dogs. AB - Detection of autoantibody, complement, or both bound to RBC is an essential requirement for unequivocal diagnosis of immune-mediated hemolytic anemia in dogs. An enzyme-linked antiglobulin test was adapted for laboratory diagnosis of this disease. The refinement and routine use of this assay have allowed further observation of the pathogenesis of the disease process. In particular, degree of hemolysis can be related to the degree of RBC sensitization associated with primary immune-mediated hemolytic anemia, and this correlation is highest for IgG autoantibody. Results indicate that autoantibody isotype might have an important role in the hemolytic process. PMID- 1586014 TI - Comparison of antigens of Pasteurella haemolytica serotype 1 grown in vitro and in vivo. AB - To determine whether antigenic differences exist in Pasteurella haemolytica serotype 1 grown in different culture conditions, the bacteria was grown on solid enriched medium, in broth culture, and in tissue chambers subcutaneously implanted in the flanks of calves. The organisms obtained by each culture method were comparable with respect to encapsulation and lipopolysaccharide content. In the bacteria grown in vivo, several unique high molecular-mass (greater than 150 kDa) protein antigens were found by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and protein immunoblotting. Bacteria grown in vitro had higher concentrations of a 49- and a 26-kDa protein than the organisms grown in vivo. The concentration of several major proteins (30, 42, 55, 71, and 100 kDa) were similar among the organisms grown by the three cultural conditions. Although the high molecular-mass antigens were unique for the chamber-grown bacteria, they were recognized by serum from a calf that had been vaccinated with formalin killed, solid medium-grown P haemolytica and were resistant to challenge exposure with the live organism. This recognition of antigens by serum from the P haemolytica-resistant calf that had been vaccinated with solid-medium-grown bacterium, indicates that the high molecular-mass antigens from chamber-grown P haemolytica may be precursors of or share antigenic determinants with other P haemolytica proteins and may not be important for consideration in vaccine formulation. PMID- 1586015 TI - Mycobacterium paratuberculosis isolated from fetuses of infected cows not manifesting signs of the disease. AB - Fetuses were obtained from 58 cows that were fecal culture-positive for Mycobacterium paratuberculosis, but were not manifesting signs of paratuberculosis. Fetal tissues from 5 of 58 cows were culture-positive for M paratuberculosis. All 5 culture-positive fetuses were from cows that were classified as heavy fecal shedders (5/28; 17.8%). Difference in prevalence of fetal infection between light (less than 70 colonies/tube) and heavy fecal shedders was significant (Fisher's exact test, P less than 0.05). Association was not evident between serologic status of the dam and prevalence of fetal infection. In infected cows without signs of paratuberculosis, fetal infection develops with lower frequency than previously reported for cows with clinical signs of the disease. In this study, fetal infection was found only in cows that were heavy fecal shedders. PMID- 1586016 TI - Colonization of the tonsils of calves with Pasteurella haemolytica. AB - Tonsils of 10 calves were inoculated with Pasteurella haemolytica (PH) and the degree of colonization was followed by collecting sequential tonsil. wash specimens. Tonsils were colonized for at least 3 weeks after instillation of PH into the tonsillar sinus. Calves with colonized tonsils responded with serum and nasal secretion antibody responses to PH and to leukotoxin. Pasteurella haemolytica was detected in nasal mucus specimens of 2 calves during the week after inoculation of the tonsils, but all other specimens were culture-negative. Infectious bovine rhinotracheitis virus-induced respiratory tract disease 25 days later did not elicit a population increase of PH in the tonsils, and did not elicit shedding of PH in nasal mucus. PMID- 1586017 TI - Experimental reproduction of swine infertility and respiratory syndrome in pregnant sows. AB - The purpose of this study was to experimentally reproduce swine infertility and respiratory syndrome (SIRS). Six multiparous sows were intranasally inoculated at 93 days of gestation with lung homogenates from clinically affected pigs, and 3 additional sows were similarly inoculated with a virus isolated in cell culture from the lung homogenate (SIRS virus, isolate ATCC VR-2332). Inoculated sows developed transient anorexia, farrowed up to 7 days prematurely, and delivered a mean of 5.8 live pigs and 6.0 dead fetuses/litter. Clinical signs of disease were not observed in 3 sham-inoculated control sows that delivered a mean of 12.7 live pigs and 0.3 stillborn fetuses/litter. The SIRS virus was isolated from 50 of 76 live-born and stillborn fetuses from the 9 infected litters. Virus was not isolated from 26 autolyzed fetuses or 15 control pigs. Six of 9 inoculated sows developed neutralizing antibodies to SIRS virus. The reproductive effects found in these experiments were identical to those found in field cases. On the basis of our findings, virus isolate ATCC VR-2332 causes the reproductive failure associated with SIRS. PMID- 1586018 TI - Development of Anaplasma marginale in male Dermacentor andersoni transferred from parasitemic to susceptible cattle. AB - The development and transmission of Anaplasma marginale was studied in Dermacentor andersoni males. Laboratory-reared male D andersoni were allowed to feed for 7 days on a calf with ascending A marginale parasitemia. The ticks were then held in a humidity chamber for 7 days before being placed on 2 susceptible calves. Anaplasmosis developed in the calves after incubation periods of 24 and 26 days. Gut and salivary glands were collected from ticks on each day of the 23 day experiment and examined with light and electron microscopy. Colonies of A marginale were first observed in midgut epithelial cells on the sixth day of feeding on infected calves, with the highest density of colonies found in gut cells while ticks were between feeding periods. The first colonies contained 1 large dense organism that subsequently gave rise to many reticulated organisms. Initially, these smaller organisms were electron-lucent and then became electron dense. On the fifth day after ticks were transferred to susceptible calves for feeding, A marginale colonies were found in muscle cells on the hemocoel side of the gut basement membrane. A final site for development of A marginale was the salivary glands. Colonies were first seen in acinar cells on the first day that ticks fed on susceptible calves, with the highest percentage of infected host cells observed on days 7 to 9 of that feeding. Organisms within these colonies were initially electron-lucent, but became electron-dense. PMID- 1586019 TI - Efficacy of an in-feed preparation of ivermectin against endoparasites and scabies mites in swine. AB - In 2 trials, the efficacy of an in-feed preparation of ivermectin was evaluated in 40 pigs naturally infected with endoparasites and Sarcoptes scabiei var suis. Treated pigs (n = 10 in each trial) were fed a ration containing 2 ppm ivermectin for 7 days, followed by consumption of a nonmedicated ration for the remainder of the trial. Control pigs (n = 10 in each trial) were fed a complete, nonmedicated ration for the duration of the trial. Pigs in trial A were monitored for 14 days after treatment; those in trial B were monitored for 35 days after treatment. In trial A, treatment efficacy of ivermectin was 100% against Ascaris suum, Physocephalus sexalatus, Oesophagostomum dentatum, O brevicaudum, Metastrongylus spp; 99.8% against Ascarops strongylina; 90.9% against Trichuris suis; and 13.1% against Macracanthorhynchus hirudinaceus. At the terminus of the trial, statistically significant (P less than 0.05) differences were observed between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Oesophagostomum spp. On posttreatment day 14, S scabiei were not found in any scrapings taken from treated pigs, but were found in scrapings from 3 of 10 control pigs. The number of infested pigs in the treatment group was not statistically different from the number of infested pigs in the control group. In trial B, treatment efficacy was 100% for A suum and Metastrongylus spp; 96.9% for Ascarops strongylina; and 76.9% for M hirudinaceus. At the terminus of the trial, statistically significant (P less than 0.05) differences were evident between numbers of treated and control pigs infected with A suum, Ascarops strongylina, and Metastrongylus spp.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586020 TI - Efficacy of milbemycin oxime against naturally acquired or experimentally induced Ancylostoma spp and Trichuris vulpis infections in dogs. AB - The efficacy of milbemycin oxime was evaluated at dosages of 0.25, 0.50, and 0.75 mg/kg of body weight in dogs naturally infected with mature Ancylostoma spp, at a dosage of 0.50 mg/kg in dogs with experimentally induced immature and mature A caninum, and at dosages of 0.55 to 0.86 mg/kg in dogs naturally infected with mature Trichuris vulpis. Milbemycin oxime was 95 and 99% effective against mature Ancylostoma spp at dosages of 0.50 and 0.75 mg/kg, respectively, but only 49% effective at a dosage of 0.25 mg/kg. Efficacy was 49% against pulmonary L3-L4 stages of A caninum (36 hours after inoculation), greater than 80% against L4 (120 hours after inoculation) and early L5 stages (216 hours after inoculation), and greater than 90% against experimentally induced mature stages (360 hours after inoculation). Milbemycin oxime was also 97% effective in the removal of mature Tr vulpis from naturally infected dogs. Adverse reactions were not observed following treatment in any of the dogs. PMID- 1586021 TI - Efficacy of ivermectin and pyrantel pamoate combined in a chewable formulation against heartworm, hookworm, and ascarid infections in dogs. AB - Eight trials were conducted in dogs to document the efficacy of ivermectin (6 micrograms/kg of body weight) and pyrantel pamoate (5 mg of active pyrantel/kg) in a beef-based chewable formulation against Dirofilaria immitis, Ancylostoma caninum, Uncinaria stenocephala, Toxocara canis, and Toxascaris leonina. Three studies involved induced infection with D immitis, and 5 studies involved induced or natural infection with hookworms and ascarids. In 3 intestinal parasite trials, the efficacy of the combination chewable tablet was compared with each of its components. Results indicated that 1 component did not interfere with the activity of the other. In 1 heartworm and 2 intestinal parasite trials, the efficacy of pyrantel, ivermectin/pyrantel combination, or ivermectin with pyrantel dosage of 10 mg/kg was evaluated. The ivermectin/pyrantel combination was 100% effective in preventing development of D immitis larvae. Efficacy of the combined product against T canis, Toxascaris leonina, A caninum, and U stenocephala was 90.1, 99.2, 98.5, and 98.7%, respectively. In the intestinal parasite trials, each individual component was found not to interfere with the anthelmintic action of the other. Increasing the dosage of pyrantel to 10 mg/kg (2 x that in the combination) did not interfere with the efficacy of ivermectin against heartworm or increase the activity of pyrantel against intestinal parasites. PMID- 1586022 TI - Electrocardiographic and echocardiographic features of trypanosomiasis in dogs inoculated with North American Trypanosoma cruzi isolates. AB - Purebred Beagles were inoculated with Trypanosoma cruzi isolates from a North American opossum or armadillo (Tc-W), and dog (Tc-D). Although Tc-D established infection in dogs, the dogs did not develop cardiac abnormalities. Dogs inoculated with Tc-W developed acute myocarditis associated with increases in P-R interval, atrioventricular block, depression of R wave amplitude and shifts in mean electrical axis. Echocardiograms were normal during this stage. Three Tc-W inoculated dogs died during the acute stage. Following the acute stage, 5 of 8 Tc W-inoculated dogs entered an indeterminate stage in which ECG changes were minor and echocardiograms were normal. Progression to the chronic stage in 5 of the 8 Tc-W-inoculated dogs was indicated by development of ventricular-based arrhythmias, mainly ventricular premature contractions, between postinoculation days 60 and 170. In some dogs, ventricular premature contractions were multifocal. Electrocardiographic abnormalities progressively degenerated to various forms of ventricular tachycardia. Worsening ECG coincided with loss of left ventricular function as measured by echocardiography. Mean percent ejection fraction and percentage of fractional shortening decreased to 63% and 52% of control values, respectively. The left ventricular free wall (LVFW) thickness decreased and % septal: % LVFW thickening ratio increased, indicating a relative preservation of septal wall motion and LVFW hypokinesis. PMID- 1586023 TI - Bioavailability of two ibuprofen oral paste formulations in fed or nonfed ponies. AB - The bioavailability and pharmacokinetics of ibuprofen, a nonsteroidal antiinflammatory drug, was studied in healthy Shetland ponies. Ibuprofen was administered IV, as a suspension, and as a solid solution oral paste to ponies from which food was withheld. The suspension paste was also administered to ponies that received hay and water ad libitum. Both formulations had an absolute bioavailability of about 80%. Bioavailability was not influenced by feeding. PMID- 1586024 TI - Evaluation of accuracy of pulse oximetry in dogs. AB - The accuracy of a pulse oximeter was evaluated over a wide range of arterial oxygen and carbon dioxide tensions, using 2 probes (finger probe and ear probe) and 2 monitoring sites (tongue and tail) in anesthetized dogs. The arterial oxygen saturation of hemoglobin (SaO2) measured directly with a multiwavelength spectrophotometer was compared with saturation estimated by pulse oximetry (SpO2). Linear regression analysis of the pooled data from 399 simultaneous measurements of SpO2 and SaO2 indicated a highly significant correlation of SpO2 with SaO2 (r = 0.97; P less than or equal to 0.0001). Although the mean difference (+/- SD) between SpO2 and SaO2 for pooled data was small (-0.06 +/- 6.8%), SpO2 tended to underestimate high SaO2 values (greater than or equal to 70%) and to overestimate low SaO2 values (less than 70%). When SaO2 values were greater than or equal to 70%, the ear probe applied to the tail was less accurate (produced a significantly greater SpO2-SaO2 difference) than the ear probe on the tongue, or the finger probe at either site. When SaO2 values were less than or equal to 50%, the finger probe applied at the tail was more accurate (produced significantly smaller SpO2-SaO2 differences) than the ear probe at either site. When SaO2 values were less than or equal to 70%, high arterial carbon dioxide tension (greater than or equal to 60 mm of Hg) was associated with greater overestimation of SaO2. PMID- 1586025 TI - Pharmacokinetics of butorphanol tartrate in rabbits. AB - The pharmacokinetic properties of butorphanol tartrate were determined in 7 rabbits after IV and SC injection (0.5 mg/kg of body weight). A 2-compartment model (biexponential) best represented the concentration vs time curve after IV injection. The half-life was calculated to be 1.64 hours via IV administration, whereas SC injection resulted in an elimination half-life of 3.16 hours. PMID- 1586026 TI - Prophylactic effect of monensin sodium against experimentally induced paratuberculosis in mice. AB - Monensin sodium (0, 15, or 30 mg/kg of complete feed) was fed ad libitum for 1 week to female mice (strain C57BL6/J) that were genetically susceptible to infection with Mycobacterium paratuberculosis. Ten mice in each of the 3 groups were inoculated intraperitoneally with M paratuberculosis (10(9) organisms). Sterile saline solution was injected intraperitoneally into 10 other mice in each group. Rations were continued for 50 days, then mice were euthanatized, and body weight, splenic weight, and hepatic weight for each mouse were recorded. Ratios of body weight to splenic weight and of body weight to hepatic weight were calculated for each mouse. Hepatic granulomas in 50 light microscopic fields were counted, and presence of acid-fast organisms in those granulomas was recorded. Infected mice given monensin had higher body weight and fewer hepatic granulomas than did mice not given monensin. Although hepatic granulomas were fewer in these mice, they contained acid-fast organisms. Effects of 15 mg of monensin and those of 30 mg of monensin/kg of complete feed were not different. PMID- 1586027 TI - Blood biochemical characteristics of cattle at sea level and at moderately high altitude (3,000 m). AB - We investigated the biochemical composition of blood from Holstein cows, native breed (criollas), and cows descended from fighting bulls (Vacas de lidia) raised at an altitude of 3,000 m (moderately high altitude, MHA), and compared the results with those from Holsteins and cows of similar genetic ancestry as the criollas (scrub cows), both raised at sea level (SL), to determine blood biochemical values characteristic of adaptation to high altitude. Only potassium and calcium concentrations were similar among groups. Glucose concentration was lower in MHA cows, with the exception of Vacas de lidia. Serum bicarbonate concentration was lower in MHA cows; this finding can be explained by hyperventilation in the hypoxic environment. Serum magnesium concentration was lower in SL and MHA Holsteins than in other groups. Serum phosphate concentration was lower in scrub cows, MHA Holsteins, and criollas than in other groups. Cholesterol concentrations were lower in SL Holsteins, whereas triglycerides were higher in scrub cows and MHA Vacas de lidia. Concentration of high-density lipoprotein was significantly greater in Vacas de lidia and less in MHA criollas than in the other groups. Uric acid and total protein were higher in MHA groups. Using radioimmunoassay for human proteins, thyroxine-binding globulin was undetectable. Total and free thyroxine and free triiodothyronine were higher in scrub cows, followed by Vacas de lidia; lower values were detected in SL and MHA Holsteins and MHA criollas. PMID- 1586028 TI - Respiratory muscle perfusion in ponies during prolonged submaximal exercise in thermoneutral environment. AB - Distribution of blood flow among various respiratory muscles was examined in 8 healthy ponies during submaximal exercise lasting 30 minutes, using radionuclide labeled 15-microns diameter microspheres injected into the left ventricle. From the resting values (40 +/- 2 beats/min; 37.3 +/- 0.2 C), heart rate and pulmonary arterial blood temperature increased significantly at 5 (152 +/- 8 beats/min; 38.6 +/- 0.2 C), 15 (169 +/- 6 beats/min; 39.8 +/- 0.2 C), and 26 (186 +/- 8 beats/min; 40.8 +/- 0.2 C) minutes of exertion, and the ponies sweated profusely. Mean aortic pressure also increased progressively as exercise duration increased. Blood flow increased significantly with exercise in all respiratory muscles. Among inspiratory muscles, perfusion was greatest in the diaphragm and ventral serratus, compared with external intercostal, dorsal serratus, and scalenus muscles. Among expiratory muscles, blood flow in the internal abdominal oblique muscle was greatest, followed by that in internal intercostal and transverse thoracic muscles, in which the flow values remained similar. The remaining 3 abdominal muscles had similar blood flow, but these values were less than that in the internal intercostal, transverse thoracic, and internal abdominal oblique muscles. Blood flow values for all inspiratory and expiratory muscles remained similar for the 5 and 15 minutes of exertion. However, at 26 minutes, blood flow had increased further in the diaphragm, external intercostal, internal intercostal, transverse thoracic, and the external abdominal oblique muscle as vascular resistance decreased. On the basis of our findings, all respiratory muscles were activated during submaximal exercise and their perfusion had marked heterogeneity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586029 TI - Thromboxane and prostacyclin production in ponies with colonic volvulus. AB - Effects of 1 hour of colonic volvulus and 3 hours of reperfusion on concentrations of thromboxane (TXB2) and prostacyclin (6-keto-PGF1 alpha) in portal, pulmonary arterial, and jugular blood were determined by radioimmunoassay to assess the site of production and clearance of these eicosanoids from the circulation in 5 anesthetized ponies. Colonic volvulus had no significant effect on mean arterial pressure or TXB2 concentrations, but significantly (P less than 0.05) increased 6-keto-PGF1 alpha concentrations in all blood samples. Immediately after colonic reperfusion, all eicosanoid concentrations were significantly (P less than 0.05) increased. Then, TXB2 returned to baseline values, whereas 6-keto-PGF1 alpha concentrations remained significantly (P less than 0.05) high for the remainder of the study. Eicosanoid concentrations were significantly (P less than 0.05) greater in portal blood than in pulmonary arterial and jugular blood samples at all periods. This suggests that the splanchnic circulation is the primary site of eicosanoid production during and after colonic volvulus and the liver appears to provide most of the circulatory clearance of thromboxane and prostacyclin. PMID- 1586030 TI - Characterization of the renal response to protein ingestion in dogs with experimentally induced renal failure. AB - Effects of a protein meal (2.7 g of casein/kg of body weight) on glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed in dogs after 15/16 nephrectomy (n = 10), and were compared with observations in dogs with intact kidneys (n = 5). Increase in GFR and RPF was observed in both groups of dogs between 1.5 and 8 hours after protein ingestion. A maximal value for GFR was observed between 4 and 5 hours after protein ingestion in dogs of both groups. Enhancement of urinary protein excretion was evident in partially nephrectomized dogs after protein ingestion (P less than 0.05), a result that was confirmed by 24-hour total urine collection from partially nephrectomized dogs fed a balanced ration. A qualitatively similar vasodilatory response was observed in partially nephrectomized dogs and in dogs with intact kidneys, and the mean maximal increase of GFR and RPF expressed as a percentage of baseline values in the latter dogs (47.0 +/- 8.1 and 43.6 +/- 10.3%, respectively) exceeded that observed in partially nephrectomized dogs (20.8 +/- 2.2 and 22.7 +/- 6.3%, respectively; P less than 0.01). The incremental response of the kidneys to protein ingestion was directly related to the degree of renal function, as reflected in the linear regression relationship between the incremental increase in GFR and the baseline value for GFR (P less than 0.01, R2 = 0.721). PMID- 1586031 TI - Correlation of serum concentration of alpha 1-acid glycoprotein with lymphocyte blastogenesis and development of experimentally induced or naturally acquired hepatic abscesses in cattle. AB - Changes in serum alpha 1-acid glycoprotein (alpha 1AG) concentration in cattle with hepatic abscesses were observed, and function of alpha 1AG was evaluated, particularly its influence on cellular immune response. Test cattle (n = 4) were inoculated with Fusobacterium necrophorum, control cattle (n = 2) were inoculated with inactivated bacteria, and naturally affected cattle (n = 11) were found in a slaughterhouse. Determination of alpha 1AG was made by use of a single radial immunodiffusion method. The action on lymphocyte blastogenesis was determined by [3H]thymidine incorporation. Cultured lymphocytes from healthy cattle were treated with variable concentrations of alpha 1AG purified from serum obtained from cattle with hepatic abscesses and suppression of blastogenesis stimulated by each of 3 mitogens was measured. In cattle with experimentally induced abscesses, serum alpha 1AG concentration increased for 7 to 10 days after F necrophorum inoculation, its change being parallel to that of sialic acid. High concentration of alpha 1AG was found in naturally affected cattle and was highly correlated to sialic acid concentration. Suppression of lymphocyte blastogenesis in cattle with experimentally induced hepatic abscesses was highly correlated to serum alpha 1 AG concentration. PMID- 1586032 TI - Effects of single-dose L-asparaginase on coagulation values in healthy dogs and dogs with lymphoma. AB - Ten healthy dogs and 10 dogs with multicentric lymphoma were given a single dose of L-asparaginase at a rate of 10,000 IU/m2 of body surface. Assessment of concentrations of contributors to the coagulation process and of the ability to coagulate including antithrombin III, one-stage prothrombin time, prothrombin proconvertin time, activated partial thromboplastin time, plasminogen, fibrinogen, and platelet number were performed prior to drug administration (day 0). These tests were repeated 24 hours (day 1), 48 hours (day 2), and 7 days after treatment with L-asparaginase. Antithrombin-III concentrations were significantly lower in the dogs with lymphoma than in healthy dogs on days 0, 1, 2, and 7; however, with the exception of day 1, mean values remained within normal limits. There was also a difference between the 2 groups in prothrombin/proconvertin values on day 7 and in platelet number on day 2, with the lymphoma group having significantly shorter prothrombin/proconvertin time than healthy dogs, and the difference in platelet numbers being associated with increased counts in the healthy dogs. Data obtained from the healthy dogs and dogs with lymphoma for each coagulation test were pooled for each treatment day (0, 1, 2, and 7), and day-0 values for each coagulation test were compared with data obtained on days 1, 2, and 7. Antithrombin-III concentration on day 7 was significantly lower than on day 0, prothrombin/proconvertin time on day 1 was significantly longer than on day 0, and fibrinogen concentrations on days 1 and 2 were significantly lower than on day 0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586033 TI - Arthrotomy versus arthroscopy and partial synovectomy for treatment of experimentally induced infectious arthritis in horses. AB - To evaluate the clinical, laboratory, and histologic effects of 2 methods of treatment for infectious arthritis in horses, Staphylococcus aureus (3.4 to 3.9 x 10(3) colony-forming units) was inoculated into the tarsocrural joints of 8 horses on day 0. Each horse was treated with phenylbutazone (2 g, PO, q 24 h) and gentamicin sulfate (2.2 mg/kg of body weight, IV, q 8 h) for 14 days. On day 2, general anesthesia was induced, and each horse had 1 tarsocrural joint treated by arthrotomy, with removal of accessible fibrin and lavage with 3 L of sterile balanced electrolyte solution. An indwelling plastic drain was placed in the standing horse to provide a means for lavage with 3 L of balanced electrolyte solution twice daily for 72 hours. The contralateral tarsocrural joint was treated via arthroscopic debridement, synovectomy, and lavage with 3 L of balanced electrolyte solution. Arthrotomy and arthroscopic portals were allowed to heal by second intention. Lameness and thermographic examinations, analysis and bacteriologic culture of synovia, CBC, and WBC differential count were performed prior to inoculation and on days 1, 3, 6, 8, and 13. On day 14, each horse was euthanatized, and the joints were measured, opened, and photographed. Synovium and articular cartilage were obtained for semiquantitative histologic (H&E stain) and histochemical (safranin O fast green stain) evaluation. Lameness and joint circumference were significantly (P less than 0.05) greater in limbs treated by arthroscopy, synovectomy, and lavage. Arthrotomy with lavage eliminated the S aureus infection significantly (P less than 0.05) earlier than arthroscopy, synovectomy, and lavage, however, both treatments eliminated the infection in all but a single joint.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586034 TI - Histologic evaluation of nerve muscle pedicle graft used as a treatment for left laryngeal hemiplegia in standardbreds. AB - A nerve muscle pedicle (NMP) graft was placed in the cricoarytenoideus dorsalis (CAD) muscle of 6 horses with induced left laryngeal hemiplegia. The NMP graft was created by use of the first cervical nerve and omohyoideus muscle. In 1 horse (control), the first cervical nerve was transected after placement of the NMP graft. One year after the surgical procedure, horses were examined endoscopically and then anesthetized. While the larynx was observed endoscopically, the first cervical nerve was stimulated. Horses were subsequently euthanatized, and the larynx was harvested. Prior to anesthesia, the endoscopic appearance of the larynx of all horses was typical of laryngeal hemiplegia. During anesthesia, stimulation of the first cervical nerve produced vigorous abduction of the left arytenoid in principal horses but not in the control horse. The right cricoarytenoideus lateralis and CAD muscles were grossly and histologically normal. Also, the left cricoarytenoideus lateralis was atrophic in all horses as was the left CAD muscle of the control horse. In contrast, the left CAD muscle harvested from principal horses had evidence of reinnervation with type 1 or type 2 fiber grouping. One year after the NMP graft procedure, horses with left laryngeal hemiplegia had reinnervation of the left CAD muscle. In another study, reinnervation was sufficient to allow normal laryngeal function during exercise. Combined, these data suggest that the NMP graft procedure is a viable technique for the treatment of left laryngeal hemiplegia in horses. PMID- 1586035 TI - Accuracy of ultrasonography in the detection of severe hepatic lipidosis in cats. AB - The accuracy of ultrasonography in detection of feline hepatic lipidosis was studied retrospectively. The following ultrasonographic criteria were associated positively with severe hepatic lipidosis: the liver hyperechoic, compared with falciform fat; the liver isoechoic or hyperechoic, compared with omental fat; poor visualization of intrahepatic vessel borders; and increased attenuation of sound by the liver. In a group of 36 cats with clinically apparent hepatobiliary disease and in which liver biopsy was done, liver hyperechoic, compared with falciform fat, was the best criterion for diagnosis of severe hepatic lipidosis with 91% sensitivity, 100% specificity, and 100% positive predictive value. PMID- 1586036 TI - Nucleotide sequence of canine c-N-ras: codons 1 to 71. AB - The c-N-ras gene has been implicated often in the genesis and/or progression of human leukemias. To our knowledge, the sequence of this gene in the dog has not been reported. Using a system of asymmetric reamplification of double-stranded polymerase chain reaction (PCR) products, we have sequenced normal canine c-N-ras mRNA from position -26 to +213, including codons 12, 13, and 61, which are the sites where oncogenic mutations are most commonly observed. The canine c-N-ras sequence has close homology with the human sequence in this area; there were only 6 observed base differences in nucleotide sequence and none resulted in a change of the encoded amino acid. The results of this study set the stage for directed searches for c-N-ras mutations in experimentally induced and naturally acquired neoplasms of the dog. PMID- 1586037 TI - Safety study of a beef-based chewable tablet formulation of ivermectin and pyrantel pamoate in growing dogs, pups, and breeding adult dogs. AB - To determine the safety of a new combination of ivermectin and pyrantel (as pamoate salt) in a novel beef-based chewable tablet formulation, 3 tolerance trials were conducted and included growing dogs, pups, and breeding adult dogs. Growing dogs, given the combination orally for 5 consecutive days at recommended dosages (5 mg of pyrantel/kg of body weight, 6 micrograms of ivermectin/kg) or at twice the pyrantel dosage in combination with the recommended dosage of ivermectin, had no adverse effects. The combination also was administered to 6 week-old pups at 1, 3, and 5 times the recommended dose on 3 successive days for 3 times in 1 month. Compared with age-matched controls, treatment had no effect on clinical status, growth rate, or gross or histologic features. Breeding male and female dogs given the combination at 3 times the recommended dose for extended periods had no adverse effects, and prevalence of abnormalities in the offspring was not greater than that in nonmedicated controls. PMID- 1586038 TI - In vivo muscle 31P nuclear magnetic resonance spectroscopy during treatment of halothane-sensitive and halothane-nonsensitive pigs. AB - In vivo muscle 31P nuclear magnetic resonance spectroscopy was performed on 10 female pigs originating from a homozygous halothane-sensitive line and on 10 female pigs from a homozygous halothane-nonsensitive line. The mean concentration of phosphocreatine in the biceps femoris muscle of the anesthetized pigs decreased to 86% of the initial value after 11 minutes of halothane exposure (3%, oxygen flow 3 L/min). After the next 5.6 minutes, phosphocreatine concentration reached a minimal value of 52%, followed by a mean recovery to 76% of the initial value during the ensuing 11 minutes. Response was not observed in anesthetized homozygous halothane-nonsensitive pigs. Thus, a decrease to 86% of the initial value of phosphocreatine was 100% predictive for homozygous halothane-sensitive pigs with body weight ranging from 10 to 18 kg. PMID- 1586039 TI - 192iridium brachytherapy, using an intracavitary afterload device, for treatment of intranasal neoplasms in dogs. AB - After surgical removal of a primary intranasal neoplasm, an implant device, designed to deliver 192iridium (192Ir) brachytherapy, was positioned in the nasal cavity of 8 dogs. Ribbons containing 192Ir seeds were placed in the device, using an afterloading technique. Dosimetry, to a dose of 7,000 to 10,000 centiGray (cGy), was calculated to encompass the site previously occupied by the tumor and a 1-cm margin of surrounding normal tissue. The quantity of 192Ir implanted varied between 16.69 and 100.80 mg of radium equivalent. The duration of implantation ranged from 90 to 168 hours. All dogs tolerated the implant well, but had a mucoid nasal discharge after radiotherapy. The implant device allowed rapid application and removal of the radioactive ribbons. Mean (+/- SD) radiation exposure to each radiotherapist during seed loading and unloading was 14.4 (+/- 5.3) and 4.5 (+/- 0.9) mrem, respectively. A uniform dose distribution around the intranasal implant device was achieved; however, dogs that received doses in excess of 9,400 cGy at the dorsolateral surface of the nose and/or hard palate had bone and soft tissue necrosis between 70 and 120 days after treatment. One dog was euthanatized 50 days after treatment because of metastatic disease, and 2 dogs were euthanatized because of local tumor recurrence at 125 and 212 days. Death, considered unrelated to treatment, occurred in 1 dog that was euthanatized 27 days after treatment and in 3 dogs that died 30, 93, and 456 days after treatment. Necropsy was performed on 3 of these dogs and evidence of intranasal neoplasia was not observed. One dog remained disease-free at 587 days after treatment. PMID- 1586040 TI - Lung albumin recovery in surfactant-treated preterm ventilated lambs. AB - Preterm ventilated animals and infants with respiratory distress syndrome (RDS) develop proteinaceous alveolar edema. To study the effect of postnatal age on intravascular radiolabeled albumin accumulation into lungs, preterm lambs at 132 days gestational age were ventilated after treatment with sheep surfactant or cow surfactant extract for periods as long as 24 h. Lambs not treated with surfactant were studied for only 5 h because of severe respiratory failure. All lambs were given radiolabeled albumin by intravascular injection 1 h before they were killed, and the net recovery of the labeled albumin was measured in the lung tissue and air space as quantified by alveolar lavage. Net 1-h radiolabeled albumin recoveries in the lungs decreased from 5 to 6% soon after birth to 0.9% at 24 h in the surfactant-treated groups (p less than 0.01). At 3 h there was less labeled albumin recovery by alveolar lavages in lambs treated with sheep surfactant than in control lambs and lambs treated with cow surfactant extract (p less than 0.05). Protein in alveolar washes from lambs treated with cow surfactant extract exceeded that in lambs treated with sheep surfactant at 3 h (p less than 0.05), but protein recoveries had decreased to similar values by 24 h, indicating a net clearance of air-space protein. These studies demonstrate a sixfold decrease in net albumin accumulation from birth to 24 h of age despite continued ventilation and oxygen exposure of the premature lamb lungs. PMID- 1586041 TI - High bronchoalveolar levels of tumor necrosis factor and its inhibitors, interleukin-1, interferon, and elastase, in patients with adult respiratory distress syndrome after trauma, shock, or sepsis. AB - Intrapulmonary activation of leukocytes and release of cellular mediators and enzymes are involved in the pathophysiology of the adult respiratory distress syndrome (ARDS). To investigate a possible role of local cytokines, we measured bronchoalveolar fluid (BALF) and plasma levels of tumor necrosis factor alpha (TNF-alpha) and its soluble inhibitors (sTNF-RI + RII), interleukin-1 beta (IL-1 beta), interferon-alpha (IFN-alpha), and granulocyte elastase in 14 patients at risk for ARDS and in 35 patients developing ARDS after trauma, sepsis, or shock. During clinical development of severe ARDS, BALF cytokines increased markedly: TNF-alpha from 116 +/- 36 to 10,731 +/- 5,048 pg/ml (mean +/- SEM), p = 0.001; sTNF-RI + RII from 3.7 +/- 1.4 to 24.6 +/- 2.6 ng/ml, p less than 0.05; and IL-1 beta from 7,746 +/- 5,551 to 42,255 +/- 19,176 pg/ml, p = 0.01. Plasma cytokines were not increased in most patients, nor were they correlated with the development or severity of ARDS. BALF elastase was higher in patients developing ARDS than in those at risk but not going into pulmonary failure (0.97 +/- 0.26 versus 0.28 +/- 0.13 U/ml, p = 0.026), and the highest values were observed in the early stages of severe ARDS (1.85 +/- 0.39 U/ml). BALF elastase levels correlated with IFN-alpha (r = 0.72, p less than 0.001). In conclusion, local release of TNF-alpha and IL-1 beta, possibly by pulmonary macrophages or other cells, and/or accumulation in the lung is associated with the development of ARDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586042 TI - Leukocyte CD11b/18 antigen-directed monoclonal antibody improves early survival and decreases hypoxemia in dogs challenged with tumor necrosis factor. AB - This study examined the effect of monoclonal antibody (MAb) directed against leukocyte CD11b/18 glycoprotein complex (904MAb) on cardiopulmonary injury induced by tumor necrosis factor (TNF), and death. Eighteen 2-yr-old, purpose bred beagles with chronic tracheostomies were challenged with TNF (60 micrograms/kg of body weight) intravenously. Nine of 18 animals were treated with 0.5 to 1.0 mg/kg of body weight 904MAb intravenously 45 min before and 12, 36, and 48 h after TNF infusion. Serial femoral and pulmonary arterial catheter hemodynamics, blood gas analysis, and radionuclide cineangiographic left ventricular ejection fractions (EF) were done before and after a fluid challenge. Serial bronchoalveolar lavages (BAL) with cell and protein analysis also were performed using the chronic tracheostomies. Compared with animals given TNF alone, animals treated with 904MAb did not differ in overall survival (TNF alone, 2/9; 904MAb, 3/9); however, the group of animals treated with 904MAb had significantly (p less than 0.01) fewer deaths within the first 30 h of TNF challenge. At 4 h after TNF challenge, all animals had significantly (p less than 0.05) reduced PaO2 after fluid challenge; however, animals given 904MAb (compared with animals given TNF alone) had significantly (p less than 0.05) smaller reductions in PaO2. Throughout the study, animals given 904MAb before TNF or TNF alone had similar changes in cardiac index, mean arterial pressure, EF, and BAL protein and neutrophil concentration. Thus, MAb directed against the leukocyte CD11b/18 glycoprotein complex prolonged survival and reduced the hypoxemia occurring after TNF challenge, but this antibody did not improve overall survival or cardiopulmonary function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586043 TI - Tumor necrosis factor-alpha production by alveolar macrophages in heart-lung transplant recipients. AB - Tumor necrosis factor-alpha (TNF alpha) is a cytokine produced by mononuclear cells that amplifies inflammation and modulates expression of Class I and Class II histocompatibility antigens. Because of these properties, this cytokine may exert a central role in both the defense and the rejection of the transplanted lung. Utilizing an ELISA technique, we measured TNF alpha in vivo and in vitro in several compartments of lung transplant recipients and in normal subjects that included serum, bronchoalveolar lavage fluid (BAL), and media conditioned by alveolar macrophages (AM) and by autologous peripheral blood monocytes (PBM). Overall, stimulated production of TNF alpha by AM from lung recipients in vitro was less than that of cells from normal subjects in response to lipopolysaccharide (LPS) challenge, and stimulated production of TNF alpha by AM harvested during conditions of infection or acute and chronic rejection was less than that by cells from healthy lung recipients. AM from normal subjects and allograft recipients produced substantially more TNF alpha than autologous PBM, but release in vitro by PBM from recipients was the same as that from cells of normal subjects who were not immunosuppressed. Thus, systemic immunosuppression does not seem to affect the production of TNF alpha by PBM in vitro, but it may reduce production by AM, indicating different effects of immunosuppression on different compartments of mononuclear cells. This mediator was not detected at elevated levels in serum, and it was undetectable in BAL fluid. We conclude that AM from lung recipients are capable of producing TNF alpha, which would influence the defense and immunogenicity of the allograft.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586044 TI - Almitrine and doxapram in experimental lung injury. AB - Almitrine and doxapram, two structurally unrelated peripheral chemoreceptor agonists, have been shown to enhance hypoxic pulmonary vasoconstriction in anesthetized dogs. We hypothesized that these drugs would increase pulmonary vascular tone and improve gas exchange in canine lung injury caused by oleic acid (OA). Pulmonary hemodynamics and gas exchange were investigated in pentobarbital anesthetized dogs before and after intravenously administered OA 0.09 ml/kg and again after placebo (n = 6), almitrine 2 micrograms/kg/min (n = 6), or doxapram 20 micrograms/kg/min (n = 6) in a randomized order. Cardiac output (Q) was manipulated using a femoral arteriovenous bypass and an inferior vena cava balloon catheter to construct mean pulmonary artery pressure (Ppa)-Q plots in order to discriminate active from passive changes in Ppa. Gas exchange was assessed by measuring arterial PO2 and intrapulmonary shunt, determined using a sulfur hexafluoride infusion. OA increased Ppa over the range of Q studied, and it deteriorated gas exchange by an increase in intrapulmonary shunt. After OA, placebo had no effect on Ppa, arterial PO2, or intrapulmonary shunt. Both almitrine and doxapram further increased Ppa at all levels of Q studied, but they did not affect indices of gas exchange after OA. We conclude that in this experimental model of acute lung injury, almitrine and doxapram induce pulmonary vasoconstriction without, however, diverting blood flow toward better oxygenated lung regions. PMID- 1586045 TI - Treatment of pulmonary arteriovenous malformations by therapeutic embolization. Rest and exercise physiology in eight patients. AB - Pulmonary arteriovenous malformations (AVM) lead to chronic hypoxemia and systemic emboli. These lesions can now be treated by catheter embolization. In order to examine physiologic abnormalities during exercise in AVM patients, and to evaluate functional improvement after therapeutic embolization, eight patients underwent detailed physiologic studies at rest and during exercise before and after therapeutic embolization. Before treatment, six patients noted dyspnea on exertion and three had symptoms suggesting paradoxical embolism. Resting studies showed hypoxemia, abnormally increased shunt fractions, chronic alveolar hyperventilation, mild decreases in diffusing capacity, and abnormal wasted ventilation (VD). During exercise, oxygenation changed little from the resting values but VD increased markedly. Functional impairment was observed in most patients, and was correlated with shunt fraction. Obliteration of the AVM was accomplished by therapeutic embolization with placement of coils or balloons in the feeder vessels. This treatment resulted in immediate relief of dyspnea and improvement in resting PaO2 and shunt fraction. Exercise studies after embolization showed improvement in exercise capacity and gas exchange. However, chronic alveolar hyperventilation and reduced diffusing capacity remained unchanged. In summary, therapeutic embolization effectively reduces the degree of shunting, with improvement in respiratory symptoms, exercise capacity, and gas exchange at rest and during exercise. The abnormally decreased diffusing capacity and increased VD suggest the presence of a diffuse pulmonary vascular abnormality, of which further study is warranted. PMID- 1586046 TI - Oxygen uptake kinetics in response to exercise in patients with pulmonary vascular disease. AB - The increase in muscular oxygen consumption that accompanies the onset of exercise is accomplished by increases in blood flow and arterial-venous O2 difference. These processes are reflected in a similar increase in pulmonary oxygen uptake (VO2), which rises in a dynamic pattern having two components and with an overall time course that may be characterized as an exponential. Because the immediate determinants of VO2 are the blood flow and respiratory gas composition in the pulmonary circulation, it was hypothesized that VO2 kinetics at exercise onset would be abnormal in patients with pulmonary vascular disease. To test this, 10 patients with pulmonary hypertension and two with pulmonary hypoperfusion caused by congenital heart disease performed constant work rate (15 +/- 16 SD watt) exercise on an upright cycle ergometer, with breath-by-breath measurement of respiratory gas exchange for determination of VO2 kinetics. The phase I increase in VO2, comprising approximately the first 30 s of exercise, was small (18 +/- 15 SD % above resting VO2). The time constant for the phase II increase in VO2 averaged 74 +/- 16 s, and the mean response time for attainment of the exercise steady state (75 +/- 17 SD s) was prolonged compared with normal values for the same work rate exercise (approximately 100 to 130% increase in phase I, and mean response time less than 25 s). In two patients who underwent surgical procedures substantially improving pulmonary hemodynamics, VO2 kinetics also improved. These findings are consistent with the concept that VO2 kinetics may be limited by pulmonary hemodynamics in the presence of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586047 TI - Oxygen delivery-independent effect of blood flow on diaphragm fatigue. AB - To determine the effect of blood flow on diaphragm fatigue independent of oxygen delivery, the left hemidiaphragm was vascularly isolated in 14 pentobarbital anesthetized, mechanically ventilated dogs. Fatigue (decline in tension generation) of the left diaphragm was induced by phrenic nerve stimulation at 10 Hz, 12/min, duty cycle of 0.5 for 8 min. Two stimulation periods separated by 30 min of rest were performed in each animal. Diaphragmatic O2 delivery during the two periods was the same. In Group 1 (n = 8), the diaphragm was autoperfused from the femoral artery (high O2-low flow) during the first stimulation period. The tension generated by the diaphragm during this period declined progressively to 47.7% of initial values. In the second period in this group, the diaphragm was pump perfused with arterial blood, diluted with an equal volume of 6% dextran at a flow rate twice that of the first period (low O2-high flow). Tension in this period declined to 76% of initial tension (p less than 0.05 compared with high O2 low flow). In Group 2 (n = 6), stimulation performed while perfusing the diaphragm in the first period with diluted arterial blood at a flow rate twice that recorded during autoperfusion (low O2-high flow) produced a decline in tension to 70% of the initial values. In the second period, the diaphragm was perfused with undiluted arterial blood at a flow rate equal to 50% of that of the first period (high O2-low flow). Tension during this period declined to 56% of initial values (p less than 0.05 compared with low O2-high flow).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586048 TI - Evaluation of human diaphragm contractility using mouth pressure twitches. AB - Mouth (PmT), esophageal (PesT), and transdiaphragmatic pressure twitches (PdiT) in response to single supramaximal bilateral phrenic nerve shocks were recorded during relaxation between total lung capacity (TLC) and functional residual capacity (FRC) in five normal volunteers. The PmT versus PesT or PmT versus PdiT relationships, which were linearly correlated (all r greater than 0.76), were not affected by diaphragm fatigue and were reproducible on repeated determinations over a period exceeding 1 yr. The PmT versus lung volume relationship was also linear (all r greater than 0.72) and reproducible, and its changes following diaphragm fatigue reliably reflected the changes in diaphragm contractility. We conclude that PmT is a reliable measure of diaphragm pressure-generating capacity in normal individuals and has the potential of providing similar information in patients. PMID- 1586049 TI - A double-blind trial of nocturnal supplemental oxygen for sleep desaturation in patients with chronic obstructive pulmonary disease and a daytime PaO2 above 60 mm Hg. AB - The efficacy of nasal oxygen during sleep was evaluated in patients with COPD, episodic rapid eye movement sleep desaturation, and a daytime PaO2 greater than 60 mm Hg. The double-blind, randomized 3-yr trial used nasal oxygen versus room air in two groups of nocturnal sleep desaturating subjects. The setting was the outpatient chest clinic of a Veterans Affairs Medical Center. There were 51 patients with moderate to severe COPD, daytime PaO2 greater than or equal to 60 mm Hg: 38 with proven REM sleep desaturation and 13 without desaturation. Nocturnal oxygen at 3 L/min was delivered by concentrator to 19 desaturating subjects, and room air at 3 L/min was delivered by defective concentrator to the remaining 19 desaturating subjects. There was no gas therapy for the 13 nondesaturating subjects. The nocturnal desaturator group who received supplemental oxygen during sleep over 36 months showed a significant downward trend in pulmonary artery pressure (-3.7 mm Hg) compared with desaturating patients treated with room air (+3.9 mm Hg). Nonvascular parameters of hypoxia, such as hemoglobin and red blood cell mass, did not differ between the sham- and oxygen-treated groups. Mortality was decidedly higher in the desaturating patients compared with non-desaturating subjects, but there was no significant difference between oxygen- and sham-treated desaturating subjects. We conclude that nasal supplemental oxygen used during sleep to reverse episodic desaturation in COPD patients whose daytime PaO2 is above 60 mm Hg has a beneficial effect in reducing pulmonary artery pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586051 TI - Spectrum of corticosteroid sensitivity in nocturnal asthma. AB - The nocturnal worsening of asthma is a common problem, and the contribution of inflammation to its pathogenesis remains unclear. We investigated the responses of 11 asthmatic subjects to overnight intravenous infusion of hydrocortisone. Prior to the study, all the subjects demonstrated clinically stable daytime asthma but persistent nocturnal worsening of spirometry. As a group, their overnight decrement in FEV1 improved from 46 +/- 4% at baseline to 12 +/- 3% (p less than 0.001) after steroid infusion. Nine of the 11 subjects demonstrated individual improvement in their overnight decrements in FEV1 of greater than 40%. The mean improvement between baseline and steroid infusion nights was 67 +/- 11%. A spectrum of response was evident, and only four of the subjects reached the normal circadian variability in overnight FEV1 measurements of less than 8%. We conclude that the nocturnal worsening of asthma often has a significant corticosteroid-sensitive component that may be both dose- and time-dependent. PMID- 1586050 TI - Specificity and sensitivity of the assay for elastin-derived peptides in chronic obstructive pulmonary disease. AB - One prediction of the protease-antiprotease hypothesis of chronic obstructive pulmonary disease (COPD) pathogenesis is the appearance of elastin-derived degradation products in the plasmas of affected patients that are due to the breakdown of alveolar interstitial elastin by an excess of elastolytic activity in the lung. We previously demonstrated a significant elevation of plasma elastin derived peptides (EDP) in subjects with COPD in comparison with asymptomatic smokers with normal spirometry or normal nonsmokers. To better determine the selectivity of the assay for EDP as a marker of COPD, we measured plasma EDP levels in different patient populations. These included subjects with COPD, subjects with diseases that may involve accelerated elastolysis (pneumonia, atherosclerotic vascular disease, and inflammatory arthritis), subjects with diseases hypothesized to involve pulmonary inflammation without elastolysis (asthma and acute tracheobronchitis), asymptomatic smokers with normal spirometry, and healthy, nonsmoking subjects. Mean plasma EDP levels in subjects with COPD were elevated above those in all other subjects (p less than 0.01). The prospective analyses of specificity and sensitivity of plasma EDP levels as markers of COPD gave values of 91 and 65%, respectively. Utilizing receiver operating characteristic curve analysis to assess the diagnostic and screening performance of plasma EDP as a test for COPD (perfect test equals an area under the curve of 1.0), the area under the curve was 0.87, which compares favorably with many widely used clinical tests. These data demonstrate that the assay for plasma EDP is a quantitative, easily measured, and highly specific marker for subjects with COPD. PMID- 1586052 TI - Increased pulmonary production of immunoreactive 15-hydroxyeicosatetraenoic acid in an animal model of asthma. AB - Airway obstruction and hyperreactivity are characteristics of human asthma and of "heaves," a naturally occurring respiratory disorder of horses and ponies. We measured pulmonary function and plasma immunoreactive 15-hydroxyeicosatetraenoic acid (i15-HETE) concentrations in simultaneously collected carotid artery and right ventricle blood samples in five affected ponies and their age- and gender matched control ponies. Measurements and sampling were performed before (Period A), during (Period B), and following recovery from (Period C) acute airway obstruction precipitated by housing ponies in a barn and exposing them to hay dust. Pulmonary resistance increased significantly, and dynamic compliance and PaO2 decreased significantly in affected ponies at Period B. Plasma i15-HETE concentrations were greater in carotid artery samples compared with right ventricle samples in affected ponies at each measurement period, suggesting that the lung was a source of i15-HETE. Carotid artery i15-HETE concentrations were significantly greater in affected ponies than in control ponies and increased at Period B. There was a significant negative correlation between changes in plasma i15-HETE and changes in dynamic compliance between measurement Periods A and B. We conclude that the lung is a source of i15-HETE in ponies with heaves, that these ponies produce greater quantities of i15-HETE than control ponies, and that exposing affected ponies to a barn environment produces acute airway obstruction and increased plasma concentrations of i15-HETE. PMID- 1586053 TI - Risk factors of soybean epidemic asthma. The role of smoking and atopy. AB - Epidemics of emergency room admissions for asthma occurring in Barcelona during the period 1981 to 1987 were caused by inhalation of soybean dust. To investigate the risk factors that determined why some asthma patients became reactive to soybean and were consequently affected by the asthma epidemics of Barcelona but others did not do so, a case-control study was conducted during 1989, 2 yr after the cessation of asthma epidemics. Patients with asthma admitted in emergency room services during epidemic asthma days (n = 169) were compared with asthma patients admitted in the same services during nonepidemic days and who were never admitted during the epidemics (n = 147). Risk factors other than soybean exposure, namely skin reactivity against at least one common allergen (odds ratio [OR] 3.0, 1.7 to 5.3), age over 64 yr (OR 2.8, 1.4 to 6.0), cigarette smoking at the time of the epidemics (OR 2.3, 1.2 to 2.4), past smoking (OR 1.8, 0.9 to 3.7), and total immunoglobulin E (IgE) higher than 100 IU/ml (OR 1.7, 1.0 to 3.0), were found independently related to epidemic asthma. The role of smoking was especially important for those who had a positive skin reaction and were exposed to soybean dust (OR 7.9, 1.8 to 36.0). In this group, a dose-response pattern with pack-years was observed (p less than 0.01). The present findings suggest a multifactorial process for epidemic asthma, in which atopy and cigarette smoking played an important synergistic role. This has a preventive potential for IgE-related asthma. PMID- 1586054 TI - Lung function, bronchial reactivity, atopic status, and dust exposure in Lancashire cotton mill operatives. AB - A total of 645 cotton mill operatives were administered a respiratory questionnaire. Of these, 85 (13.2%) complained of one or more work-related respiratory symptoms: 23 (3.6%) had byssinosis and the remaining 62 had symptoms not conforming to byssinosis (nonbyssinotic symptomatics, NBS). All byssinotic, 56 NBS, and 84 matched asymptomatic operatives underwent pulmonary function testing (FEV1 and FVC), skin testing to common allergens, and histamine bronchial challenge. Work area and personal breathing zone cotton dust concentrations were assessed, and a cumulative cotton dust exposure index was calculated for each individual. Byssinotic, NBS, and asymptomatic operatives all had reduced FEV1; observed mean liters (95% CI); predicted mean: byssinosis, 2.36 (2.09 to 2.63), 3.02; NBS, 2.94 (2.71 to 3.17), 3.29; and asymptomatic, 3.12 (2.95 to 3.29), 3.31. Only byssinotic subjects had evidence of impaired FVC: 3.31 (2.97 to 3.65), 3.69. The majority of byssinotic operatives (18 of 23) had bronchial hyperreactivity (BHR) in comparison with 21 of 56 NBS and 14 of 84 asymptomatic operatives. Mean log PD20 (95% CI) values were significantly lower in the byssinotic group -0.72 (-1.42, -0.02) than in NBS 0.57 (0.08, 1.06) and asymptomatic subjects 0.57 (-0.26, 1.39). The distribution of atopy did not differ significantly between groups, and lung function did not differ significantly between atopic and nonatopic subjects. The cumulative cotton dust exposure index was the only dust parameter to be significantly greater in those with BHR (mean mg-yr/m3 [95% CI] 14.13 [13.1 to 15.1]) than those with normal reactivity [5.35 (3.9 to 6.8)]. PMID- 1586055 TI - Effect of pattern of aerosol inhalation on clearance of technetium-99m-labeled diethylenetriamine pentaacetic acid from the lungs of normal humans. AB - The clearance rate of inhaled aerosols of technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) from the lungs provides a rapid, clinically useful, noninvasive index of pulmonary epithelial permeability. In order to identify a method that minimizes intrasubject and intersubject variability and thereby provides a reliable means to identify patients with abnormal values, we administered a submicronic aerosol of 99mTc-DTPA to 10 healthy, nonsmoking male subjects with either tidal breathing (Vtidal) or multiple vital capacity maneuvers (VVC). Subjects then spontaneously breathed room air while counting continued for 30 min. Monoexponential clearance rates over 7, 15, and 30 min were compared with a two-compartment, biexponential analysis over 30 min. Intrasubject reproducibility was evaluated by repeating clearance 2 to 156 days later. Monoexponential clearance following VVC at 30 min equaled 1.36 +/- 0.55%/min compared with 0.83 +/- 0.25%/min for Vtidal (p less than 0.025). VVC inhalations resulted in a larger fast compartment of 16 +/- 12% compared with 3 +/- 2% with tidal breathing (p less than 0.01). The least intrasubject variability with coefficient of variation (CV) of +/- 18% was obtained with monoexponential analyses after Vtidal during 15 min of scanning and with either breathing maneuver over 30 min. Monoexponential clearance for 30 min with Vtidal gave the least scatter between subjects, with CV of +/- 30%. These data show that simple tidal inhalations of 99mTc-DTPA followed by a monoexponential analysis of the 30-min time-activity curve from both lungs minimize the degree of variability between and among subjects and provide a predicted normal value of clearance of 0.83 +/- 0.25%/min. The development of a more rapid curvilinear clearance followed by delivery VVC suggests that several deep breaths transiently increase epithelial permeability or reduce the volume of liquid in the alveolar subphase in some regions. Resting for 20 min prior to inhaling the aerosol of 99mTc-DTPA is recommended to avoid alterations in clearance rates from deep breathing. PMID- 1586056 TI - Nebulizer function during mechanical ventilation. AB - In the setting of mechanical ventilation, recent studies have cast doubt on the ability of nebulizer systems to deliver adequate amounts of medication. We therefore studied ventilator-related and nebulizer-related factors that could potentially affect the amount of aerosol inhaled by an intubated subject. Utilizing two separate protocols, we used a bench model of a ventilator circuit, radiolabeled (technetium pertechnetate, 99mTc) saline droplets and a filter technique to measure the percentage of radioaerosol delivered. First, we compared four commercially available jet nebulizers and found that there were significant differences in rate of aerosol production between systems, ranging from 3 to 37%. Delivered aerosol was measured at different ventilator settings, and it was found that the duty cycle can potentially influence output by sevenfold. Some nebulizers were also sensitive to changes in the initial volume of solution placed in the nebulizer. The inclusion of a humidification device significantly reduced output by a mean of 41 +/- 3.5%, but it did not affect particle distribution. Endotracheal tube diameter was not an important variable. Then, with the effects of the above variables established, a separate series of experiments was performed to test whether the use of different radiolabeling compounds can confound the measurement of inhaled drugs. Two nebulizers (AeroTech II and Twin Jet) and pentamidine as the test drug were studied with fixed ventilator settings, treatment time, endotracheal tube size, and volume fill. No humidification was used. The nebulizer solution was labeled with 99mTc, which was bound to either human serum albumin (HSA) or sulfur colloid (SC).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586057 TI - Acute health effects of PM10 pollution on symptomatic and asymptomatic children. AB - This study assessed the association between daily changes in respiratory health and respirable particulate pollution (PM10) in Utah Valley during the winter of 1990-1991. During the study period, 24-h PM10 concentrations ranged from 7 to 251 micrograms/m3. Participants included symptomatic and asymptomatic samples of fifth- and sixth-grade students. Relatively small but statistically significant (p less than 0.01) negative associations between peak expiratory flow (PEF) and PM10 were observed for both the symptomatic and asymptomatic samples. The association was strongest for the symptomatic children. Large associations between the incidence of respiratory symptoms, especially cough, and PM10 pollution were also observed for both samples. Again the association was strongest for the symptomatic sample. Immediate and delayed PM10 effects were observed. Respiratory symptoms and PEF changes were more closely associated with 5-day moving-average PM10 levels than with concurrent-day levels. These associations were also observed at PM10 levels below the 24-h standard of 150 micrograms/m3. This study indicates that both symptomatic and asymptomatic children may suffer acute health effects of respirable particulate pollution, with symptomatic children suffering the most. PMID- 1586058 TI - The effect of maternal smoking during pregnancy on early infant lung function. AB - We studied the effect of prenatal maternal cigarette smoking on the pulmonary function (PF) of 80 healthy infants tested shortly after birth (mean, 4.2 +/- 1.9 wk). Mothers' prenatal smoking was measured by: (1) questionnaire reports at each prenatal visit of the number of cigarettes smoked per day, and (2) urine cotinine concentrations (corrected for creatinine) obtained at each visit. Infant PF was assessed by partial expiratory flow-volume curves and helium-dilution measurement of FRC. Forced expiratory flow rates were significantly lower in infants born to smoking mothers, both when unadjusted and after controlling for infant size, age, sex, and passive exposure to environmental tobacco smoke (ETS) between birth and the time of PF testing. Flow at functional residual capacity (VFRC) in infants born to smoking mothers was lower than that found in infants whose mothers did not smoke during pregnancy (74.3 +/- 15.9 versus 150.4 +/- 8.9 ml/s; p = 0.0007). Differences remained significant when flow was corrected for lung size (VFRC/FRC: 0.87 +/- 0.26 versus 1.77 +/- 0.12 s-1; p = 0.013). No differences in pulmonary function were evident among infants exposed and unexposed to ETS in the home after stratifying by prenatal exposure status. We conclude that maternal smoking during pregnancy is associated with significant reductions in forced expiratory flow rates in young infants. The results suggest that maternal smoking during pregnancy may impair in utero airway development and/or alter lung elastic properties. We speculate that these effects of maternal prenatal smoking on early levels of forced expiratory flow may be an important factor predisposing infants to the occurrence of wheezing illness later in childhood. PMID- 1586059 TI - Longitudinal effects of passive smoking on pulmonary function in New Zealand children. AB - In this study we examined the longitudinal effects of smoke exposure on lung function in a cohort of New Zealand children observed from 9 to 15 yr of age. Possible exposures included in utero exposure from mothers smoking during pregnancy, passive smoke from parents, and active smoking by the children. Lung function measures of forced expiratory volume in one second (FEV1) and vital capacity (VC) were measured biennially and ratios (FEV1/VC) were computed. The data were analyzed using longitudinal methodology, and all subjects with at least one pulmonary function test and responses to the questions concerning smoke exposures were included (n = 634). Subjects reporting wheeze or asthma were examined as a separate subgroup. In the whole cohort, no significant detrimental effects were detected for absolute FEV1 or VC in either sex, related to active or passive smoke exposures. Parental smoking was, however, associated with persistent but mild and nonprogressive impairment of the FEV1/VC ratio in males, an effect that was present at the time lung function measurements were first made. This effect was not seen in females. In children with reported wheeze or asthma, parental smoking had progressive, more serious, and clinically significant effects on the FEV1/VC ratio among adolescents of both sexes, causing a mean reduction in FEV1/VC ratios by age 15 of 3.9% in males and 2.3% in females, in contrast to the observed increase in FEV1/VC ratios with age seen in nonexposed wheezing children. We conclude that passive smoking is a major contributing factor to the development and persistence of airflow limitation in wheezing children. PMID- 1586060 TI - A search for mycobacterial DNA in granulomatous tissues from patients with sarcoidosis using the polymerase chain reaction. AB - We have used the polymerase chain reaction as a tool to detect the presence of mycobacterial DNA from organisms of the Mycobacterium tuberculosis complex and other species of mycobacteria in samples from patients with sarcoidosis. Using systems based on the amplification of a fragment of the gene coding for the 65-kD mycobacterial antigen, which were demonstrated to detect approximately 20 mycobacterial genomes/microgram total DNA, DNA from M. tuberculosis was reproducibly identified in DNA extracted from granulomatous tissues from two patients with sarcoidosis, but could not be detected in DNA extracted from tissue biopsies (n = 16) or cells recovered by lavage (n = 6) from most sarcoid patients or from control subjects (n = 22). Using a system based on the amplification of a fragment of the IS6110 insertion element, which could reliably detect two genomes of mycobacterial DNA/microgram total DNA, no additional positive results were observed. In an effort to identify another species of Mycobacterium present in granulomatous tissues from sarcoid patients but not control tissues, a fragment of the 65-kD mycobacterial antigen was amplified and then reamplified using "nested" primers recognizing sequences that are highly conserved among mycobacteria and closely related species, and the amplified DNA products were cloned and sequenced. Amplified DNA was observed in a minority of samples from patients and control subjects (32/84 and 34/77 attempts, respectively, p greater than 0.2), resulting from amplification of DNA from at least 17 different organisms.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586061 TI - Evaluation of the clinical usefulness of mycobacterial skin test antigens in adults with pulmonary mycobacterioses. AB - A double-blind, multicenter study was conducted to evaluate the usefulness of mycobacterial skin test antigens for the specific diagnosis of adult pulmonary mycobacterial disease. The skin test antigens used were PPD-T (M. bovis) and PPD B (M. intracellulare), made bioequivalent to 5 TU PPD-S through bioassay in human subjects. Of the 192 adults (18 yr of age or older), those with disease caused by M. tuberculosis (MTB) had significantly larger reactions to PPD-T than did those with disease caused by nontuberculous mycobacteria (NTM) or those with negative culture results (NEG)(13.41 mm versus 4.87 and 4.96 mm, respectively, p less than 0.001). The mean induration to PPD-B in NTM was not different from that in MTB or NEG. Defining a "positive" to be greater than or equal to 10 mm induration and a size difference of greater than or equal to 3 mm between PPD-T and PPD-B, the sensitivity, specificity, and positive predictive value (PPV) for PPD-T in diagnosing MTB versus NTM was 29, 90, and 75%. Corresponding values for PPD-B and NTM disease were 70, 61, and 64%. Dual testing was less useful in distinguishing disease caused by any of the mycobacteria from NEG. Although the sensitivity of PPD-B, made bioequivalent to PPD-S, was high, the specificity and PPV were low. We conclude that this preparation of PPD-B is no more useful in distinguishing adult pulmonary disease caused by NTM than is PPD-T alone. PMID- 1586062 TI - Pulmonary function and immunologic abnormalities in miliary tuberculosis. AB - In a group of 33 patients with miliary tuberculosis (MTB), pulmonary function testing and bronchoalveolar lavage (BAL) were each performed in 31. The arterial blood gas analysis was done in 13 patients. Mild restrictive ventilatory defect, hypoxemia, and hypocapnia were observed. BAL revealed lymphocytic alveolitis. The lymphocyte subsets were measured in the BAL fluid and peripheral blood in 10 patients. The helper lymphocytes were decreased in the peripheral blood and increased in the BAL fluid. The immunoglobulins (IgG, IgA, and IgM) were significantly increased in the peripheral blood and BAL fluid in 18 patients. Serum complement (C3) (n = 23) and BAL fluid fibronectin (n = 22) were also significantly increased. Lymphocytic alveolitis and the raised levels of IgG and IgA in the peripheral blood and BAL fluid persisted at the end of 9 months of standard chemotherapy for tuberculosis. Long-term studies with larger numbers of patients are required to monitor the course of alveolitis in MTB. An addition of corticosteroids to the antituberculosis drug regimen may be considered in the treatment of these patients. PMID- 1586063 TI - Intrapulmonary bacterial clearance of type III group B streptococcus is reduced in preterm compared with term rabbits and occurs independent of antibody. AB - Intrapulmonary clearance of type III group B streptococcus (GBS) and related phagocytic recruitment was studied in preterm and term rabbits at 4 and 8 h after aerosol infection using left lung homogenates to quantify GBS and right lung bronchoalveolar lavage (BAL) to recover phagocytes. Opsonophagocytosis of type III GBS by pulmonary alveolar macrophages (PAM) was studied in vitro with a modified differential fluorescence-quenching method using PAM lavaged from preterm, term, and adult rabbits. Sera of experimental animals were tested for opsonization of type III GBS using fluorescein-labeled antibodies to rabbit IgG and C3. Although term animals showed some clearance at 8 h, preterm animals had marked intrapulmonary proliferation of GBS. The number of PAM in BAL fluid was 20 fold higher in term than in preterm rabbits at 0 h, but by 8 h, preterm rabbits had a large influx of PAM, whereas PAM remained constant in term BAL fluid. Rates of phagocytosis of GBS were twice as high in term versus preterm PAM during in vivo and in vitro studies. Among PAM from term and adult animals, opsonization of GBS with MgEGTA-sera promoted phagocytosis in vitro at levels comparable to pooled adult sera, whereas opsonization with EDTA-sera resulted in a significantly lower rate of ingestion. None of the experimental animals' sera were able to deposit IgG, but all deposited C3 on the surface of GBS. In summary, preterm rabbits had a diminished bronchoalveolar PAM population that did not ingest GBS as well via the alternative complement pathway when compared with term rabbits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586064 TI - Regional sensitivity of human airways to capsaicin-induced cough. AB - To examine the sensitivity of different parts of the human respiratory tract to a tussive and bronchoconstrictor stimulus, randomized, standardized single breaths of capsaicin aerosols were inhaled by nine healthy, nonsmoking subjects. A small droplet aerosol (3.2 microns MMD) was inhaled slowly (0.25 L/s), and a large droplet aerosol (5.2 microns MMD) was inhaled rapidly (1.0 L/s) to optimize differences in deposition, which were assessed after inhalation of 99mTc-DTPA aerosols with similar characteristics. Both capsaicin aerosols (zero to 256 microM) produced a concentration-dependent cough response. The geometric means (95% Cl) for the concentrations causing two coughs (cough threshold) were 2.3 microM (1.1 to 4.9) and 8.7 microM (3.1 to 24.5) (p less than 0.02), respectively, with the small and large droplet aerosols. The concentrations causing five coughs were 5.5 microM (3.0 to 10.0) with the small droplet aerosol and 29.5 microM (8.3 to 104.7) with the large droplet aerosol (p less than 0.02). In contrast, FEV1, measured 2 min after the largest concentration of capsaicin, was not significantly altered by any of the two capsaicin aerosols. In each subject, a similar dose was deposited in the larynx with both aerosols, whereas the dose deposited in intrapulmonary airways was 2.3 times larger with the small droplet aerosol. This study confirmed that slow inhalation of a small droplet aerosol produced a more peripheral airway deposition than did rapid inhalation of a large droplet aerosol. The small droplet aerosol was four times more potent, and capsaicin-sensitive sensory neurons mediating cough seem, therefore, to be present in human intrapulmonary airways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586065 TI - Primary pulmonary hypertension in association with human immunodeficiency virus infection. A possible viral etiology for some forms of hypertensive pulmonary arteriopathy. AB - Recent reports have suggested a possible association between HIV-1 infection and primary pulmonary hypertension (PPH), but most of the patients described to date have either had acquired immunodeficiency syndrome (AIDS) with concurrent lung infections or have administered Factor VIII intravenously for hemophilia. We report three human immunodeficiency virus type 1 (HIV-1)-positive homosexual white males with clinical and hemodynamic diagnoses of PPH. None of the patients had any opportunistic lung infections or other pulmonary pathology, nor were they hemophiliacs. They had no histories of intravenous drug use. Lung tissue from two of the patients revealed hypertensive arteriopathy consistent with PPH and no other pulmonary pathology. Attempts at localizing HIV-1 infection to the vascular endothelium with electron microscopy, immunohistochemistry, DNA in situ hybridization, and polymerase chain reaction techniques did not reveal direct pulmonary artery infection with the virus. These data and the finding of tubuloreticular structures on electron microscopy suggest that HIV-1 may play a role in the pathogenesis of these cases of PPH through mediator release associated with HIV-1 infection rather than by direct endothelial infection. PMID- 1586066 TI - Lack of smooth muscle in the small pulmonary arteries of the native Ladakhi. Is the Himalayan highlander adapted? AB - Chronic hypobaric hypoxia induces a mild degree of pulmonary arterial hypertension with structural alterations in the peripheral portions of the pulmonary arterial tree of the native Andean highlanders. On the other hand, animals indigenous to high altitude do not show these changes and are adapted to hypobaric hypoxia. The small pulmonary arteries of seven native Himalayan highlanders were examined at autopsy and found to be thin-walled with no medial hypertrophy of the muscular pulmonary arteries or muscularization of the arterioles. These findings suggest that the Himalayan highlanders may be adapted to hypobaric hypoxia. PMID- 1586067 TI - Nonoccupational beryllium disease masquerading as sarcoidosis: identification by blood lymphocyte proliferative response to beryllium. AB - Chronic granulomatous lung disease caused by industrial exposure to beryllium continues to occur, but no community cases have been reported in more than 30 yr. With the advent of a blood screening test that detects beryllium sensitization, physicians can discriminate chronic beryllium disease from sarcoidosis. A 56-yr old woman in whom sarcoidosis was diagnosed had an unremarkable occupational history, but her husband was a beryllium production worker. Blood and bronchoalveolar lavage lymphocyte transformation tests, measuring the beryllium specific cellular immune response, were abnormal, confirming a diagnosis of chronic beryllium disease. Chronic beryllium disease continues to occur in the nonoccupational setting and among bystanders in industry, masquerading as sarcoidosis. Because even transient or possibly low levels of exposure may cause disease, this case has important implications for how clinicians, industry, and government agencies define the populations at risk of chronic beryllium disease. PMID- 1586068 TI - Improvement in gas exchange with nasal continuous positive airway pressure in pulmonary alveolar microlithiasis. AB - A 37-yr-old man with pulmonary alveolar microlithiasis (PAM) presented with respiratory failure and cor pulmonale. The FEV1/FVC was 1.4/1.8 L with total lung capacity of 3.2 L using the helium dilution method (54% predicted) and 6.1 L using body plethysmography (102% predicted), indicating large noncommunicating regions. The KCO (transfer factor per liter lung volume) was 3.05 ml/min/mm Hg/L (47% predicted). Despite home oxygen (3 L/min) and diuretic therapy, the patient remained hypoxic (PaO2, 55 mm Hg) and incapacitated with dyspnea. Nasal continuous positive airway pressure (nCPAP) at 12 cm H2O and oxygen at 1 L/min improved his oxygenation (PaO2, 93 mm Hg), and introduction of this regimen at night resulted in subjective improvement in daytime function. A Grandjean right heart catheter was introduced at the bedside, and the multiple inert gas elimination technique (MIGET) was used to measure ventilation and blood flow distributions at ambient pressure and with the addition of 10 cm H2O nCPAP. The patient had severe pulmonary hypertension (mean Ppa, 57 mm Hg) and severe hypoxemia (PaO2 37 mm Hg), which was mainly due to shunt (16% of cardiac output) and a broadening of the main mode of the ventilation-perfusion (VA/Q) distribution (log SD Q, 0.94). There was a significant reduction in shunt during nCPAP to 6% of cardiac output without increasing Ppa, and this effect appeared to extend past the period of application. We conclude that nCPAP reduces intrapulmonary shunt in this rare condition and allows for correction of hypoxemia with a smaller oxygen flow rate. PMID- 1586069 TI - Occupational asthma caused by a hardener containing an aliphatic and a cycloaliphatic diamine. AB - An otherwise healthy 44-yr-old man experienced a serious attack of bronchial obstruction after working with resins and hardeners, releasing fumes of a mixture of an alipathic and a cycloaliphatic diamine hardener. Eight hours after deliberate challenge with the hardener a large increase of airway resistance was found. Seventy-two hours after challenge, eosinophilia in the bronchoalveolar lavage (BAL) fluid together with a decrease of peripheral eosinophils was seen. After cessation of contact with this hardener, no more acute episodes occurred, although maintenance treatment with a topical corticosteroid and a beta 2-agonist remained necessary. A BAL performed 1 yr later showed a normal cell distribution. The results suggest that these aliphatic and cycloaliphatic diamine hardeners may be occupational hazards. Eosinophil inflammation may play a causal role. PMID- 1586070 TI - Inspiratory muscle work of breathing during flow-by, demand-flow, and continuous flow systems in patients with chronic obstructive pulmonary disease. AB - The effect of flow-by continuous positive airway pressure (CPAP) in comparison with continuous-flow (CF) CPAP on inspiratory muscle work of breathing (WI) in intubated patients is not known. We hypothesized that WI during flow-by CPAP would be comparable with that during CF CPAP. In nine intubated male patients recovering from acute respiratory failure related to chronic obstructive pulmonary disease, we compared the effects of flow-by, demand-flow, and CF CPAP on WI. We also evaluated the extent to which the addition of 5 cm H2O of pressure support to demand-flow CPAP (DF-PS5) decreases WI. At CPAP levels of zero and 8 cm H2O, flow-by, demand-flow, DF-PS5 were applied in random order followed by CF CPAP for 15 min each. WI (expressed as Joules per liter and Joules per minute), maximal airway pressure drop during inspiration (delta Paw), total lung resistance (RL), lung compliance (CL), and ventilatory variables were measured. At CPAP of zero cm H2O, WI with flow-by was comparable with CF CPAP, and significantly less than with demand-flow CPAP. At both CPAP of zero and 8 cm H2O, the addition of 5 cm H2O PS to demand-flow CPAP reduced WI significantly to a level comparable with that of flow-by CPAP. At both CPAP levels, delta Paw was the largest, with demand-flow CPAP. RL and CL were not significantly different between the different CPAP systems. We conclude that WI with flow-by CPAP is comparable with that with CF CPAP, and significantly less than with demand-flow CPAP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586071 TI - Pyrazinamide sterilizing activity in vitro against semidormant Mycobacterium tuberculosis bacterial populations. AB - Previously, we reported that pyrazinamide has very poor bactericidal activity against M. tuberculosis growing in broth at pH 5.6. In the present study, cultivation at pH 4.8 to 5.0 in 7H12 broth prevented an increase in the number of viable bacteria, but the cultures remained metabolically active. The presence of 50 micrograms/ml pyrazinamide in semidormant cultures led to a sharp decline in the number of viable bacteria, by more than 1,000-fold. This unfavorable environment probably made the bacilli especially vulnerable to pyrazinamide, whose mode of action remains unclear. To distinguish this effect of pyrazinamide on the semidormant bacteria from its mostly bacteriostatic activity against actively multiplying bacteria, we suggest interpreting the in vitro effect as "sterilizing." PMID- 1586072 TI - Detection of cryptococcal antigen in bronchoalveolar lavage fluid: a prospective study of diagnostic utility. AB - Cryptococcal pneumonia is associated with significant morbidity and mortality in immunocompromised patients. We examined the utility of screening bronchoalveolar lavage (BAL) fluid for cryptococcal antigen. In a pilot study, we found that cryptococcal antigen was always positive in unprocessed BAL specimens of seven patients with cryptococcal pneumonia and negative in 44 patients with other granulomatous diseases who acted as the control subjects. A prospective study was done of 220 immunocompromised patients (188 with human immunodeficiency virus infection, 32 with other causes of immunosuppression) undergoing BAL for fever and pulmonary symptoms. The eventual diagnosis of cryptococcal pneumonia was made in eight patients. All eight patients had a cryptococcal antigen titer greater than or equal to 1:8. There were four patients without cryptococcal pneumonia who had cryptococcal antigen titers of 1:8, there were none with higher titers. For a titer of cryptococcal antigen titer of greater than or equal to 1:8, there was 100% sensitivity, 98% specificity, a positive predictive value of 67%, and a negative predictive value of 100%. The measurement of cryptococcal antigen in the BAL can be a rapid, simple way to make a diagnosis of cryptococcal pneumonia in immunosuppressed patients with pneumonia. PMID- 1586073 TI - NHLBI workshop summaries. Neuroimmune interactions in the lung. PMID- 1586074 TI - NHLBI workshop summaries. Pleural cell biology in health and disease. PMID- 1586075 TI - Antigen-induced proliferative response of lavage and blood T lymphocytes. PMID- 1586076 TI - "Tastes great, less filling". The debate about mycobacteria and sarcoidosis. PMID- 1586077 TI - Improved outcome based on fluid management in critically ill patients requiring pulmonary artery catheterization. AB - We performed a randomized, prospective trial to evaluate whether fluid management that emphasized diuresis and fluid restriction in patients with pulmonary edema could affect the development or resolution of extravascular lung water (EVLW), as well as time on mechanical ventilation and time in the intensive care unit (ICU), in critically ill patients requiring pulmonary artery catheterization (PAC). PAC was performed on 101 patients. A total of 52 patients were randomized to an EVLW management group using a protocol based on bedside indicator-dilution measurements of EVLW. The other 49 patients were randomized to a wedge pressure (WP) management group in whom fluid management decisions were guided by WP measurements. A total of 89 patients had pulmonary edema (defined as EVLW greater than 7 ml/kg ideal body weight). Except for a clinically unimportant difference in mean age, the two groups were entirely comparable at baseline. The study groups were managed differently, as evidenced by cumulative input-output of 2,239 +/- 3,695 ml (median = 1,600 ml) in the WP group versus 142 +/- 3,632 ml (median = 754 ml) in the EVLW group (p = 0.001). EVLW decreased significantly, and ventilator-days and ICU days were significantly shorter only in patients from the EVLW group. No clinically significant adverse effect occurred as a result of following the EVLW group algorithm. Thus, a lower positive fluid balance, especially in patients with pulmonary edema regardless of cause, is associated with reduced EVLW, ventilator-days, and ICU days. PMID- 1586079 TI - An in vitro model for studying the effects of slime and nonslime-forming Staphylococcus epidermidis contamination of intravenous catheters. AB - An in vitro model was developed to study the relationship between intravenous catheters, bacteria, and the subcutaneous tunnel. Studies of both slime-forming and nonslime-forming coagulase negative Staphylococcus epidermidis show that slime formation enhances capillary action of coagulase negative S. epidermidis. This offers a possible explanation of the increased virulence associated with slime-forming coagulase negative S. epidermidis in the clinical situation. PMID- 1586078 TI - A controlled clinical comparison of four different surfactant preparations in surfactant-deficient preterm lambs. AB - Four pulmonary surfactant preparations (natural sheep surfactant, Exosurf, Infasurf, and Survanta) were compared with no treatment in 29 newborn lambs at 126 +/- 1 days gestation. Fetuses were delivered by Cesarean section under general anesthesia and treated with either the manufacturer's recommended dose of a commercial surfactant, 100 mg phospholipid/kg of natural sheep surfactant, or no surfactant (control group). Lambs were mechanically ventilated with 100% oxygen until moribund from respiratory failure or until killed at 24 h after delivery. Lambs surviving to 12 h received surfactant retreatment (of the same type) if hypoxemic. All lambs were surfactant deficient at birth, having less than 0.1 mg/ml of phospholipid measured in the lung liquid. All control lambs developed early respiratory failure and died within 8 h after delivery. Survival was significantly prolonged by natural surfactant (p less than 0.02), Infasurf (p less than 0.0001), and Survanta (p less than 0.02). Natural surfactant, Infasurf, and Survanta significantly improved arterial oxygenation and ventilatory compliance compared with no treatment. These effects lasted as long as 24 h in lambs given Infasurf, but no more than 6 h in lambs given natural surfactant or Survanta. After death, static pressure-volume lung mechanics were significantly better for lambs given natural sheep surfactant, Infasurf, or Survanta. Lambs given Exosurf were no different than control lambs in any variable measured. Thus, in 126-day gestation surfactant-deficient newborn lambs, natural sheep surfactant, Infasurf, and Survanta, but not Exosurf, Improve oxygenation, lung mechanics, and survival. PMID- 1586080 TI - Complications of pelvic fractures from blunt trauma. AB - Significant external forces are required to fracture a normal pelvis. These forces usually result from rapid deceleration or crushing injuries, and energy often is delivered to multiple anatomic sites in addition to the pelvis. Associated injuries are common, and numerous complications can occur in patients with pelvic fractures. During 4 years, the authors treated 144 men and 92 women with pelvic fractures from blunt trauma who were admitted directly to the University of Mississippi Medical Center. They had a mean age of 31.5 years, a mean Injury Severity Score of 21.3, and an average hospital stay of 16.8 days. Seventy-seven of the 236 patients (32.6%) had 137 complications, including 18 deaths. Most of these were infections such as pneumonia (6), urinary tract infections (8), wound infections (8), or sepsis without a defined source (10). There was a high incidence of pulmonary complications including Adult Respiratory Distress Syndrome (12), significant atelectasis (7), and fat emboli (3). Musculoskeletal complications (13) and coagulopathy (12) also occurred frequently. Eight patients had thromboembolic events, but prophylactic, subcutaneous heparin was not beneficial in preventing these complications. Patients with complications had higher Injury Severity Scores, lower Trauma Scores, increased transfusion requirements, longer hospital stays, and greater hospital charges compared to those without complications (P less than 0.01 for all variables). There was no association of complications with patient age, sex, mechanism of injury, anatomic site or amount of displacement of the pelvic fracture, or vector of injury. Patients with unstable pelvic fractures were much more likely to have complications than were those with stable pelvic fractures (P = 0.013).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586081 TI - Vascular complications following intra-aortic balloon pump insertion. AB - The intra-aortic balloon pump (IABP) has been used for 23 years to treat cardiogenic shock from various causes. A retrospective review was conducted to evaluate the morbidity, mortality, and risk factors associated with insertion of this device. Over a recent 3-year period, 415 such pumps were inserted either by percutaneous (323) or cut-down (92) technique in 404 patients. Indications for placement included intraoperative pump failure (46%), cardiac instability before coronary artery bypass grafting (28%), perioperative support (13%), cardiac transplantation (7%), and cardiogenic shock (6%). Noncardiac vascular complications occurred in 67 patients, 55 per cent of whom required surgical correction. Operative procedures included femoral artery thrombectomy, bypass grafting, fasciotomy, and amputation. Major risk factors for vascular complications included diminished or absent femoral pulses on initial examination, being a woman, and obesity. In patients with known peripheral vascular disease, the risk of a vascular complication was 17.9 per cent when a surgical cut-down technique was used to insert the IABP, and 38.9 per cent when a percutaneous insertion was performed. The mortality doubled in those patients who had a vascular complication as compared to those who did not (34% vs 17%). A more liberal use of an open surgical technique in those patients with peripheral vascular disease, obesity, and who are women may help to reduce complications after the insertion of the intra-aortic balloon pump. PMID- 1586082 TI - One-day hospitalization following modified radical mastectomy. AB - Postoperative management of patients following modified radical mastectomy has changed dramatically in recent years. Historically, patients usually remained in the hospital with closed suction drainage until the amount of drainage had decreased sufficiently for them to be removed. The feasibility of early discharge on the day following surgery was studied in a prospective manner in 29 consecutive breast cancer patients; 27 underwent unilateral modified radical mastectomy and 2 bilateral mastectomies by a single surgeon. All patients were instructed before surgery about planned early discharge and drain care. Twenty seven of 29 patients (93.3%) were discharged the day following surgery. However, 2 patients refused discharge and were discharged on postoperative Day Two, and one patient was readmitted for confusion. Drains were removed in the office an average of 5.07 days after surgery. Forty-five per cent of patients developed a seroma that required aspiration at least once. No significant long-term sequela were experienced as a result of early discharge. The average hospital cost was reduced by $2,474.00 or 36 per cent (P less than 0.001) as compared to other surgeons in the same medical center who held to traditional postoperative care. The authors conclude that discharge on the day following surgery for patients undergoing a modified radical mastectomy is safe and cost effective. PMID- 1586083 TI - Clinical results of piezoelectric gallstone lithotripsy. AB - The safety and efficacy of piezoelectric extracorporeal shockwave lithotripsy in the treatment of symptomatic gallbladder stones were evaluated in 53 consecutively treated patients. All treatments were performed as outpatients without anesthesia; over 95 per cent of 109 treatments were performed without analgesia or sedation. Ursodeoxycholic acid was administered post-treatment. Seventy per cent of patients had multiple sessions. Cumulative stone-free rates of 38 per cent at 6 months, 65 per cent at 12 months, and 75 per cent at 15 months were achieved. There was no difference in eventual stone clearance between patients with single stones less than 20 mm diameter, single stones greater than or equal to 20 mm diameter, or multiple (two or three) stones, although patients with single smaller stones required significantly fewer total shocks to become stone-free (P = .02). Stone clearance correlated with estimated stone volume. Biliary pain occurred in 62 per cent of patients after treatment but ceased in stone-free patients. Biliary complications of pancreatitis (7.5%) and choledocholithiasis (3.8%) were successfully treated by endoscopic papillotomy. Nonbiliary complications were virtually nonexistent. Three patients (5.7%) had elective cholecystectomy. Results indicate that piezoelectric lithotripsy is a safe, minimally painful treatment that, in conjunction with oral bile acids, can produce stone-free rates of 75 to 100 per cent in selected patients. PMID- 1586084 TI - Prevention of stress gastritis with tissue preservation solution. AB - Stress gastritis frequently occurs in association with shock or sepsis. Gastric mucosal ischemia appears to be a key feature in these critically ill patients. The University of Wisconsin cold preservation solution (UWS) is an isoosmolar, nonglucose-based perfusate that minimizes hypothermia-induced cell swelling and prevents intracellular acidosis and oxygen-free radical injury, while providing high energy substrates for donor organs. In a prospective, single-blind study, 18 similar Sprague-Dawley rats were randomly divided to receive only 5 per cent dextrose and water (D5W) (Group 1) or a 50 per cent solution of D5W+UWS (Group 2) for 72 hours. At the end of 72 hours the animals were stressed by the cold restraint model. The mean number of ulcers for Group 2 was nearly half that of Group 1. Also, Group 2 had a significantly lower mean total ulcer length (P less than 0.005) and ulcer index (P less than 0.05). Most of Group 2 had mild gastritis changes (grade 0 to 1), while more than half of Group 1 had severe gastritis (grade 3). Gastric mucosal pH was similar for both groups. Topically applied UWS appears to reduce the severity and incidence of stress gastritis in this experimental model. Because mucosal pH values were similar, it is thought that UWS may alter the effects of gastric mucosal ischemia at a cellular level. PMID- 1586085 TI - The safety of mesh repair for primary inguinal hernias: results of 3,019 operations from five diverse surgical sources. AB - Initial attempts by surgical pioneers to repair hernias with prosthetic mesh met with failure because of faulty materials. As a result, surgeons experienced anxiety about performing this procedure. This anxiety persists, despite the present availability of new, safe patches and sutures. It was the unacceptably high failure rate of standard methods of repair for recurrent hernias that led to the use of plastic screens to bolster such repairs. However, persistent reluctance to use mesh for primary hernioplasty continued. Within the past two decades, true, tension-free patch repair of primary inguinal hernias without suture closure of hernial margins has been examined and clarified, and the technique has been perfected. In 3,019 reported primary inguinal hernias so treated by five different groups, there have been no mesh rejections, a 0.2 per cent recurrence rate, and insignificant incidence of infection. A new era of hernia repair appears to be at hand; therefore, such results warrant a new look at inguinal hernia repair. PMID- 1586086 TI - Diagnosis and treatment of enterovesical fistulae. AB - Presenting symptoms, diagnostic progression, etiology, therapy, and complications of 44 patients with enterovesical fistulae who came to three Yale teaching hospitals over a 9-year period were reviewed. Patients with diverticulitis as the cause of their fistula were older and came to the hospital with pneumaturia/fecaluria. Patients with pelvic cancer were more likely to have fecaluria, gastrointestinal symptoms, or hematuria. Patients with Crohn's disease were an average of 20 years younger than the patients with cancer or diverticulitis and they came to the hospital with pneumaturia, abdominal pain, abdominal mass, and tenderness. Computerized axial tomography scanning, cystoscopy, charcoaluria, and barium enema were useful in making the diagnosis; intravenous pyelography and colonoscopy were not. One-tenth of the patients were not candidates for operation, and one-quarter of the patients did not undergo complete operative resolution with restoration of enteric and urinary continuity. Nine patients underwent a two-stage repair consisting of resection/repair of the fistula with proximal fecal diversion and subsequent re-establishment of bowel continuity. These patients had a higher morbidity than the 19 patients who underwent one-stage repair. Enterovesical fistula is a challenging entity, the etiology of which may be suspected upon taking the patient's history or performing the physical assessment; however, the definitive diagnosis of enterovesical fistula can remain elusive. Single-stage repair can be achieved with low morbidity and mortality in many candidates. PMID- 1586087 TI - Balancing the normal appendectomy rate with the perforated appendicitis rate: implications for quality assurance. AB - Debate continues as to what should be the appropriate "negative" appendectomy rate for patients suspected of having acute appendicitis. The controversy centers around balancing the complications of appendectomy for a normal appendix with those for a perforated appendix. By using a decision analysis approach to the probable outcomes of appendectomy for a normal appendix, acute appendicitis, and perforated appendicitis, this study provides one answer to this question. These outcomes are based on a review of the results of over 10,000 appendectomies. There is an inverse relationship between the normal appendectomy rate and perforated appendicitis rate. The overall complication rate in patients suspected of having appendicitis improved when the rate of perforated appendicitis was lowered, even if this meant raising the negative appendectomy rate. The perforation rate seemed to level off at approximately 10 per cent. The quality of surgical care delivered to a given population should not be judged solely on the normal appendectomy rate, but this rate should be interpreted in the light of the perforated appendicitis rate. Quality assurance assessments should focus first on perforated appendicitis and only later on normal appendectomy. PMID- 1586088 TI - The double-staple technique in colorectal anastomoses: a critical review. AB - The widespread availability and use of stapling devices have changed colorectal surgery. In 1980, Knight and Griffen developed the "double-staple" technique, using a circular stapler to transect a linear rectal staple line. This eliminated the need for a hand-sewn, distal purse string, which was sometimes difficult or even impossible to accurately place low in the pelvis. To evaluate this procedure, the authors have reviewed their results with the double-staple technique over the past 5 years. One hundred four patients underwent this procedure between 1985 and 1990 at Thomas Jefferson University Hospital (Philadelphia, PA). There were 60 men and 44 women, with a mean age of 62.4 years. Seventy-two patients underwent operation for carcinoma of the rectum or sigmoid. Thirty-five of these had preoperative radiation therapy. Other diagnoses included 1) diverticular disease, 2) rectal prolapse, 3) villous adenoma, 4) endometrial carcinoma, 5) fistula, 6) stricture, 7) Crohn's disease, 8) colonic endometriosis, 9) lymphoma, 10) ovarian carcinoma, and 11) ulcerative colitis. Incomplete "donuts" were observed in 5 patients. Diverting colostomies were performed in 23 patients, ileostomies in 3. Postoperative complications relating to the double-staple technique itself included a rectovaginal fistula in 1 patient. There were 3 clinical leaks (2.8%), all treated nonoperatively. No strictures were observed. As previously observed, the authors believe the double staple technique offers certain advantages over traditional, hand-sewn and stapled anastomoses, for instance: 1) there is significantly less contamination, 2) the anastomosis is technically easier, and 3) bowel segments of different diameters can be easily anastomosed. PMID- 1586089 TI - The irritable bowel syndrome: mechanisms and a practical approach to management. AB - OBJECTIVE: To develop a practical strategy that facilitates the management of patients with the irritable bowel syndrome (IBS). STUDY SELECTION AND DATA EXTRACTION: Review of the pertinent literature published in major English language journals for the last 25 years, describing the pathophysiology and treatment of subgroups of patients with IBS. RESULTS: A stepwise approach for practical management of patients with suspected IBS is identified. The first step includes a combination of positive diagnosis of symptoms with limited investigations to exclude underlying structural or biochemical disorders. In the second step, therapeutic trials focus on alleviating the predominant symptoms. For patients with intractable symptoms, the third step combines novel tests to assess altered function and therapeutic trials to correct the dysfunction identified in the individual patient. CONCLUSIONS: A practical approach has been developed for management of IBS. It is based on advances in our understanding of the mechanisms resulting in IBS and on targeting therapy to correct the dysfunctions in these patients. PMID- 1586090 TI - The irritable bowel syndrome: review and a graduated multicomponent treatment approach. AB - The irritable bowel syndrome is a common chronic disorder having a broad clinical spectrum of severity. Although only a small proportion of those afflicted seek medical help for their symptoms, a subset have severe and intractable symptoms. A positive diagnosis should be established from the history and physical examination; endoscopic and radiologic investigations should be minimized. We suggest that the physician also assess the severity of the illness based on its symptomatic and functional features and the patient's behavioral response. Classifying the disorder in this manner permits a graduated treatment approach that emphasizes education, reassurance, and dietary adjustment for mild symptoms. Moderate symptom severity requires, in addition, identification and modification of factors exacerbating symptoms, psychotherapeutic and behavioral techniques and, if a certain symptom type predominates, pharmacologic agents directed toward the presumed gastrointestinal motor dysfunction. For severe symptoms, physician based behavior modification and psychopharmacologic agents are helpful. When the disorder is intractable, referral may be needed, for example, to a pain treatment center. In all cases, the skillful physician must ensure continued psychosocial support to enhance coping and continued focus on the palliative aspects of care rather than on cure. PMID- 1586091 TI - Low-dose amiodarone for atrial fibrillation: time for a prospective study? AB - Because atrial fibrillation is associated with substantial morbidity, restoration of sinus rhythm is desirable. Long-term maintenance of sinus rhythm often requires chronic antiarrhythmic therapy. Class I antiarrhythmic drugs such as quinidine or propafenone maintain sinus rhythm in approximately 50% of patients at 1 year and have risks for proarrhythmia and noncardiac toxicity. Studies of low-dose amiodarone for atrial fibrillation have reported sinus rhythm maintenance in 53% to 79% of patients during a mean follow-up of 27 months. Amiodarone has a lower incidence of proarrhythmia and heart failure exacerbation compared with class I drugs. Most noncardiac side effects are dose related, and low-dose amiodarone (less than 300 mg/d) is well tolerated. The time has come for a large-scale prospective evaluation of low-dose amiodarone treatment early in the course of atrial fibrillation. PMID- 1586092 TI - Osler, Lyman, and Page: a tale of three texts. PMID- 1586093 TI - Management of the irritable bowel syndrome: different views of the same disease. PMID- 1586094 TI - Statements on electronic publication and on peer-reviewed journals. International Committee of Medical Journal Editors. PMID- 1586095 TI - Interpreting CAGE scores. PMID- 1586096 TI - GM-CSF in Hodgkin disease. PMID- 1586097 TI - GM-CSF in Hodgkin disease. PMID- 1586098 TI - Beta-lactam antibiotics and vitamin K. PMID- 1586099 TI - Playing God--revisited. PMID- 1586100 TI - Playing God--revisited. PMID- 1586101 TI - Playing God--revisited. PMID- 1586102 TI - Playing God--revisited. PMID- 1586103 TI - Playing God--revisited. PMID- 1586104 TI - Quality-of-life evaluation in a clinical trial of zidovudine therapy in patients with mildly symptomatic HIV infection. The AIDS Clinical Trials Group. AB - OBJECTIVE: To evaluate the effects of zidovudine therapy in patients with mildly symptomatic HIV infection using Q-TWiST (quality-adjusted: Time Without Symptoms and Toxicity). DESIGN: Analysis of a previously reported multicenter, randomized, placebo-controlled clinical trial. SETTING: Thirty-two AIDS Clinical Trial units. PATIENTS: A total of 351 patients with mildly symptomatic HIV infection were assigned to placebo, and 360 patients were assigned to zidovudine, 1200 mg/d. MEASUREMENTS: A modified Q-TWiST method for comparing treatments based on time spent without severe symptomatic adverse events and without disease progression. Zidovudine and placebo were compared in a threshold utility analysis considering reduction in quality of life associated with adverse events and disease progression. Adverse events defined by laboratory findings were distinguished from findings representing symptomatic events. RESULTS: The incidence of severe symptomatic adverse events was 22.8% for the zidovudine group and 15.1% for the placebo group (P = 0.01), but, as previously reported, zidovudine improved progression-free survival relative to placebo (at 18 months, 91% compared with 81%; P = 0.001). In an 18-month period, patients receiving zidovudine went an average of 14.5 months without disease progression or a severe symptomatic adverse event compared with 14.7 months for placebo. The zidovudine group gained 0.9 months without disease progression but lost 1.1 months due to adverse events. Within the 18-month observation period, treatment provided more Q-TWiST than placebo if the quality of life after HIV disease progression was assumed to be 10% to 20% worse than the quality of life after a severe symptomatic adverse event. CONCLUSIONS: The Q-TWiST analysis projects that quality-of-life reductions due to severe symptomatic adverse events might be balanced by the quality-of-life benefits of delayed HIV disease progression for patients who received zidovudine for mildly symptomatic HIV infection. At currently recommended doses (500 to 600 mg/d, half the dose used in this study) zidovudine therapy is likely to yield a more favorable result. PMID- 1586106 TI - Myocardial infarction caused by cardiac microvasculopathy in a patient with the primary antiphospholipid syndrome. AB - Antiphospholipid antibodies occur in various clinical states, including the primary antiphospholipid syndrome. Clinical features in these conditions appear to be caused by vasculopathy associated with the presence of these antibodies. We report the case of a patient with primary antiphospholipid syndrome who experienced cardiac necrosis secondary to myocardial microvasculopathy in the absence of vasculitis. This case demonstrates unequivocally that noninflammatory myocardial microvasculopathy occurs in the primary antiphospholipid syndrome per se without any clinical or immunologic signs of systemic lupus erythematosus or other disease process. The histopathologic findings in the skin and myocardial biopsies showed a noninflammatory vasculopathy characterized by bland thrombi and lack of infiltration of the vessel wall by inflammatory cells. Ultrastructural examination of the myocardial biopsy confirmed the vascular thrombosis and endothelial activation and showed no deposits in basement membranes. The patient survived after appropriate treatment. Evidence presented here supports the concept that the vasculopathy in the antiphospholipid syndrome is distinct from other types of vascular occlusions seen in systemic lupus erythematosus. We suggest that myocardial biopsy can be crucial in showing an underlying myocardial ischemic process despite "normal" findings on coronary angiography. Results of the biopsy hastened the decision to use potentially lifesaving plasmapheresis and anticoagulation therapy in this patient. PMID- 1586105 TI - Physiologic testosterone levels in normal men suppress high-density lipoprotein cholesterol levels. AB - OBJECTIVE: To investigate the role of physiologic levels of testosterone in the control of lipoproteins in healthy men. DESIGN: A double-blind, randomized study. SETTING: A university community. PARTICIPANTS: Fifteen healthy men, ages 20 to 36 years. INTERVENTION: We induced acute, reversible hypogonadism in five normal men by administering daily subcutaneous injections of the gonadotropin-releasing hormone (GnRH) antagonist, Nal-Glu, for 6 weeks. Another group of five normal men received Nal-Glu plus weekly injections of testosterone enanthate, 100 mg/wk, thereby maintaining normal serum testosterone levels. Five additional men received placebo injections. MEASUREMENTS: Plasma lipids, including high-density lipoprotein (HDL) subfractions HDL2 and HDL3, apoprotein A1, and serum levels of gonadotropins, estradiol, and testosterone were measured before, during, and after treatment. RESULTS: At the end of the treatment period, HDL cholesterol levels in men receiving Nal-Glu increased by 26% (95% CI, 18% to 34%; P less than 0.05). Levels of HDL2, HDL3, and apoprotein A1 increased by 63% (CI, 16% to 110%), 17% (CI, 3% to 31%), and 17% (CI, 5% to 29%), respectively (P less than 0.05 for each parameter). Total cholesterol increased by 12% (CI, 2% to 22%). Low density lipoprotein (LDL) cholesterol and triglyceride concentrations did not change. No statistically significant changes occurred in any lipid measurement in men receiving Nal-Glu plus androgen replacement or placebo (P greater than 0.05). CONCLUSIONS: Experimental hypogonadism induced by administration of a GnRH antagonist results in a statistically significant increase in HDL cholesterol, including HDL2 and HDL3. These effects are most likely due to decreased androgen levels because they are reversed by administration of antagonist together with testosterone. Our results imply that androgen levels in the normal adult male range have a suppressive effect on HDL cholesterol concentration and may contribute to the increased risk for coronary artery disease in men. PMID- 1586108 TI - Screening hospital employees for measles immunity is more cost effective than blind immunization. AB - OBJECTIVE: To examine alternative strategies in developing a cost-effective program to assure measles immunity among hospital employees. DESIGN: Observational. SETTING: Referral teaching hospital. PARTICIPANTS: Eighteen hundred "established" hospital employees with potential patient contact and 630 newly hired hospital employees. INTERVENTIONS: Established employees born after 1 January 1957 and all newly hired employees were screened for serologic evidence of measles immunity and immunized if necessary. MEASUREMENTS: Cost analysis. RESULTS: The cost of screening and directed immunization of established employees was $3.98 per employee compared with a potential cost of $10.03 to $42.80 per employee if all employees were "blindly" immunized with monovalent measles vaccine or trivalent mumps-measles-rubella vaccine. The cost of the screening and directed immunization of new employees was $2.42 per employee compared with potential costs of $8.30 to $39.34 per employee for blind immunization. These analyses assumed that varying percentages of employees would be able to produce documentation of having received a previous dose of vaccine or of having had measles. CONCLUSIONS: In a large referral hospital, screening for measles immunity followed by directed immunization was considerably less expensive than immunizing all potentially susceptible employees. PMID- 1586107 TI - Splenic radiation for corticosteroid-resistant immune thrombocytopenia. AB - OBJECTIVE: To determine the role of splenic radiation as a treatment for immune thrombocytopenia. DESIGN: Retrospective analysis of an open, nonrandomized investigation. SETTING: A regional cancer center, referred care, and primary care settings. PATIENTS: Eleven older patients with idiopathic thrombocytopenic purpura (ITP) and 8 patients with secondary immune thrombocytopenia refractory to corticosteroid treatment for whom surgery would have posed a high risk. INTERVENTION: A short course (1 to 6 weeks) of radiation therapy to the spleen (total dose, 75 to 1370 cGy) with or without concurrent and postradiation corticosteroid administration. MEASUREMENTS: Efficacy was assessed by measuring any increase in the platelet count and by monitoring the duration of response and side effects. RESULTS: Of 11 patients with ITP, 8 patients responded. Three patients had a sustained (greater than 52 weeks) increase in the platelet count to safe levels after therapy was discontinued. An additional patient had a sustained response but required intermittent, low-dose corticosteroids. Four other patients had increases in their platelet counts that lasted from 8 to 25 weeks. Two of the eight patients without ITP had a positive response, whereas four did not respond, and two were not evaluable. Patients had no adverse reactions to the radiation treatment. CONCLUSION: Splenic radiation can be a safe and effective method to raise the platelet count in older patients with ITP that is refractory to corticosteroids and in whom the risks associated with splenectomy are high. PMID- 1586109 TI - Increased prevalence of migraine and chest pain in patients with primary Raynaud disease. AB - OBJECTIVE: To investigate the prevalence of headaches and recurrent chest pain in patients with primary Raynaud disease. DESIGN: Postal survey. SETTING: Raynaud disease clinic at the Lahey Clinic Medical Center, a tertiary care hospital. PARTICIPANTS: A consecutive series of 120 patients with primary Raynaud disease who had been observed for at least 2 years, 97 of whom received and 93 of whom completed the questionnaire, and a control group of 93 age- and sex-matched hospital employees without Raynaud phenomenon. RESULTS: Migraine was diagnosed in 57 (61%) patients with primary Raynaud disease and in 21 (23%) of the control group (odds ratio, 5.4; 95% CI, 2.8 to 10.3). Migraine with aura and migraine without aura were more common in patients with Raynaud disease than in the control subjects (27% compared with 5%; P less than 0.001 and 34% compared with 17%; P = 0.008, respectively). Nonmigrainous headaches were more common in the control group (51% compared with 25%; P = 0.003). Chest pains were reported by 44 (47%) of the patients with Raynaud disease and by 15 (16%) of the control group (odds ratio, 4.4; CI, 2.4 to 9.3). Chest pains were more frequently reported by patients with Raynaud disease who had migraine (34 of 57, 60%) than by patients without migraine (10 of 36, 28%; P = 0.003). CONCLUSIONS: An increased prevalence of migraine was found in patients with primary Raynaud disease. Chest pain, often diagnosed as musculoskeletal or nonspecific, was common in patients with primary Raynaud phenomenon, especially in patients who had coexisting migraine. PMID- 1586110 TI - Results of bone densitometry affect women's decisions about taking measures to prevent fractures. AB - OBJECTIVE: To describe how the results of bone densitometry affect women's decisions about measures to prevent fractures and to determine whether labeling women as having below-normal bone density has adverse effects. DESIGN: Mail survey of a random sample of women. SETTING: Four community hospitals in the San Francisco Bay area. PATIENTS: A total of 261 women (response rate, 81.3%) who had undergone bone densitometry. MEASUREMENTS: Bone densitometry and self-report of changes in attitude and behaviors. RESULTS: Fifty-three percent of the women reported that their first bone density measurements were below normal, and 44% said that they were diagnosed as having osteoporosis on the basis of their test results. Women who reported that their bone density measurements were below normal were much more likely than women with normal results to begin some type of measure to prevent fractures (94% compared with 56%; P less than 0.01), to start hormone therapy (38% compared with 8%; P less than 0.01), and to take precautions to avoid falling (50% compared with 9%; P less than 0.01). Women reporting low bone density, however, also became more fearful of falling (38% compared with 2%; P less than 0.01) and limited their activities to avoid falling (24% compared with 2%; P less than 0.01). CONCLUSIONS: The results of bone densitometry substantially influence women's decisions about beginning estrogen replacement therapy and other preventive measures for osteoporotic fractures. The potential effects of labeling a woman as having below-normal bone density need to be considered before densitometry is widely used for unselective screening of women. PMID- 1586111 TI - Typhlitis in patients with HIV-1 infection. PMID- 1586112 TI - Internal medicine curriculum reform. PMID- 1586113 TI - Changing the curriculum for internal medicine residency training. AB - The academic leadership of internal medicine is considering fundamental changes in the curriculum for internal medicine residency training. The impetus to change the curriculum is derived from various socioeconomic changes during the past 10 years. These changes have resulted in a drastically shortened length of stay of patients in hospitals, an emphasis on outpatient care by reimbursement agencies, and a sharp decline in the numbers of U.S. medical graduates selecting careers in internal medicine. Curriculum change will mandate that we define the roles of general internists and subspecialists in the delivery of primary care and that we re-define how we train these two groups of internists. We must focus attention on the issue of service compared with education and must confront the issue of how best to train foreign medical graduates. Any curriculum change will also have to accommodate residents selecting careers in research in order to ensure an adequate supply of physician-scientists. Before implementing any change in curriculum, we must put into place a rigorous, prospective evaluation system. We must be able to accurately assess both positive and negative outcomes of these changes and make necessary midcourse corrections. The impetus for curriculum change in internal medicine will, it is hoped, ultimately benefit the public, the trainees, and the practice of internal medicine. PMID- 1586114 TI - Internal medicine practice in transition. Implications for curriculum changes. AB - The curriculum for internal medicine needs to be changed to eliminate the dichotomy between training and practice. At the same time, changing medical needs and the actual conditions of medical practice must be taken into account. The new curriculum, at the very least, needs to emphasize the central position of general internists in health care delivery. To accomplish this, several subjects must be added to the curriculum, including additional training in ambulatory care, management of chronic disease, medical procedures, and the doctor-patient relationship. Learning to direct a coordinated health care team should also be included. A more definitive restructuring would require reorganizing medical centers around three major departments: primary care, subspecialty medicine, and surgery. PMID- 1586115 TI - What is a curriculum? AB - Dissatisfaction with the current internal medicine residency experience has led to proposals for various new curricula. Unfortunately, the more basic question of "What is a curriculum?" or more accurately, "What curriculum model is most appropriate for clinical training?" has remained largely unexamined. The dominant curriculum model, although valuable, may not be adequate for the task. In its place we propose an experimental model that is more congruent with the realities of graduate medical education. PMID- 1586116 TI - General internal medicine in internal medicine: at the core or on the periphery? AB - In the past decade, faculty in sections of general internal medicine have assumed responsibility for training residents, for staffing clinical practices, and for developing new domains of health services and effectiveness research. These activities form the core of internal medicine: They are integral to the role of internal medicine as an academic and patient care discipline, and they complement the activities of the internal medicine subspecialties. The effect of general internal medicine on internal medicine, therefore, has been to shift the focus away from the subspecialty services--which compartmentalize a patient's medical problems--and back to the concept of the patient as a "whole" person. The role and territory of the general internist are changing as a result of this shift in focus, and general internal medicine is emerging as the new core discipline in internal medicine. These changes have allowed for an expanded capacity of internal medicine to provide new services, modified curricula, and innovative research. PMID- 1586117 TI - Relation of the internal medicine residency and the medical school curriculum. AB - Students should have contact with faculty members in internal medicine throughout their medical education. Faculty internists should play a role in admission of students, in the basic science courses of the first year of medical school, and in the introductory course to clinical medicine and pathophysiology of the second year of medical school. The core medical clerkship is not an academic advertisement and should not be designed specifically to attract students to internal medicine. The core clerkship is designed for all students, regardless of their intended specialty and should include inpatient and outpatient care in a context and at a pace that allow time for reflection, reading, and problem solving. The advanced medicine experience should give students at least a glimpse of the mastery of the discipline of internal medicine. For students entering internal medicine, the fourth year of medical school and first year of residency could be combined to improve the content and quality of both. PMID- 1586118 TI - Do we still need primary care tracks? AB - Primary care tracks in internal medicine residency programs were initiated in the late 1970s in response to the need for more primary care physicians. These programs have shown that internists can be trained effectively in ambulatory settings. Graduates of primary care tracks are more likely to choose careers in general internal medicine than are other internal medicine graduates. Primary care internist training has been accompanied by the growth of academic general internal medicine divisions and by the enhancement of the scientific base for ambulatory care practice and medical education. Expanded ambulatory training opportunities, modeled after current primary care tracks, should be offered to all residents in internal medicine. At the same time, primary care tracks should be revised to address deficiencies in current ambulatory training. These tracks should be designed to commit most resident time to ambulatory care settings, to involve residents in community-based and interdisciplinary health care, and to expose residents to conditions outside of the medical sector that affect health. Revised primary care tracks can serve as pathfinder programs for ongoing reform in internal medicine residency training. Three models for organizing and funding such reform are presented. PMID- 1586119 TI - Ambulatory-based residency education: improving the congruence of teaching, learning, and patient care. AB - Residency education in internal medicine should be based in the ambulatory setting. The challenge in ambulatory education lies not only in the unique opportunities afforded by the setting but also in the careful implementation of a program based on sound educational principles. We have designed a new ambulatory based model of internal medicine residency that adheres to the principles of adult learning theory. Four aspects of the proposed residency model are discussed: the setting, the teaching-learning model, the curriculum, and the schedule. Potential barriers to implementation of the model are reviewed, and solutions are suggested. Residency programs in internal medicine are at an important crossroad. Either we can substantially change the programs' content and focus, or we can risk the continued unpopularity and "second-class" status of the programs among medical students. Internal medicine needs to be recognized and accepted as a fundamental primary care discipline to justify continued public support in an era of overspecialization. PMID- 1586120 TI - The matrix of ambulatory education. AB - Ambulatory education has become an essential part of all internal medicine residencies. To develop excellent ambulatory education programs, we must thoroughly understand the opportunities available in such a setting, and the leaders in internal medicine must be willing to experiment with nontraditional locations and rotational formats. An "ambulatory matrix" can be constructed by program directors to help define the educational opportunities available in their institutions and to map the possibilities for educational rotations outside of the hospital wards. PMID- 1586121 TI - Alternative pathways for training the general internist and the medical subspecialist. AB - Considerable attention is being directed from within the discipline of internal medicine to a perceived need for changes in the curriculum for postgraduate training of the internist. Much of this attention has been focused on the training required to properly prepare the general internist for the evolving system of health care. A proposal is presented to change the pattern of training of both the general internist and the medical subspecialist. After 2 years of core training, the general internist would enter 2 additional years of training that would include new material and additional experience in areas such as ambulatory and continuity care. After the core experience, the subspecialist would begin training in the subspecialty. The general internist would be certified as such, and the subspecialist would be certified only in the subspecialty. The proposal is based on the assumptions that 1) more general physicians are needed to meet the nation's health care needs; 2) more time will be required to properly train the general internist; 3) all of the additional and expanded training experiences for the generalist are not essential for training the subspecialist; and 4) the generalists of the future will not come from the ranks of subspecialists. The training needs of the general internist and the subspecialist should be viewed as separate, and curriculum changes should be considered without the restrictions of current patterns of training. PMID- 1586122 TI - The accelerated internal medicine program at the University of Kentucky. AB - Concern is growing about the ability of categorical medicine residency programs, structured within academic health centers, to provide balanced, progressive, postgraduate internal medicine education. Detrimental factors, including over representation of critically ill patients, shortened length of hospitalization, stress, discontinuity between undergraduate and graduate training, rotational assignments driven by hospital service imperatives, and total costs, may all negatively affect internal medicine residency education. Therefore, an experimental accelerated internal medicine (AIM) curriculum combining 3 years of undergraduate with 3 years of graduate internal medicine education has been initiated by the Department of Medicine and the College of Medicine at the University of Kentucky. After completion of the third year and during the first 13 months of the AIM curriculum, selected students are rotated through an integrated series of educational experiences that incorporate all of the requirements for graduation from medical school and progressively advance the students' skills, knowledge, and responsibilities to that of a second-year resident. Thereafter, the curriculum is similar to that of the categorical residents, except that more ambulatory care and off-site rotations are interspersed to better provide the educational experiences representative of the practice of internal medicine. Evaluations of the first groups of AIM residents indicate that their performance has equaled that of the control residents who graduated after 4 years from the College of Medicine. Furthermore, the AIM residents report general acceptance by their fellow residents and attending physicians and report no undue stress in making the transition. PMID- 1586123 TI - Development of a didactic curriculum in science related to internal medicine. AB - To best prepare physicians for productive careers in medicine and to instill in them a lifelong commitment to learning, a didactic curriculum for the sciences should be incorporated in training programs. Such a curriculum can be effective only if it can be woven into the fabric of clinical experiences and it is seen by the housestaff as relevant to their needs. A new level of commitment by our clinical teachers and a reassessment of the allocation of time for learning will be required. PMID- 1586124 TI - Training internists in procedural skills. AB - The procedural skills of internists have been scrutinized recently because of concern for quality of care and because of economic and liability issues. The findings of recent surveys of program directors and practicing internists about procedural skills are reviewed. The results of these surveys in relation to the American Board of Internal Medicine's (ABIM) new training requirements and New York State's new policy requiring credentialing of residents in training are also discussed. Surveys show that internists do a large number and variety of procedures, that the number of procedures varies with the nature and location of practice, and that internists who more recently completed training do more procedures. Many graduates do not master the procedures their program directors think they should, and many learn procedures, often without supervision, after they have entered practice. The ABIM has recently ruled that residents must have documented experience and competence in specific core procedures to become eligible for certification. Also, New York State, in the wake of the Libby Zion case, now requires that all residents be credentialed in the procedures they do during training. Programs in internal medicine need to decide which procedures their residents will master and assure that their residents receive the training and testing necessary for competency and for formal certification of mastery in each procedure. Programs may restructure rotations to assure adequate experience. In the new era of accountability, certification of training and of competence in procedural skills will be an important function of training programs. PMID- 1586125 TI - Teaching preventive medicine and health maintenance. AB - Preventive health care is an important part of the practice of internal medicine but is poorly taught and practiced in most residencies. A successful curriculum would impart knowledge of the preventive health care guidelines recommended by expert groups; provide opportunities for residents to understand the conceptual basis of preventive care; expose residents to clinical faculty with positive attitudes toward prevention; help residents to learn skills in physical examination, screening tests, and counseling in behavioral modification relevant to prevention; and provide a practice environment in which high-quality preventive health care is possible. All of the skills can be learned as other aspects of medicine are now learned--under the guidance of capable and respected faculty teaching at the bedside, in the clinics, and during ward rounds and conferences. PMID- 1586126 TI - Recruitment of minority physicians into careers in internal medicine. AB - Despite some initial success in the early 1970s, the important goal of increasing the numbers of underrepresented minorities in medical school and on medical faculties has stalled short of proportionate representation. To further the current efforts of the Association of Professors in Medicine (APM) and other national medical groups that are devoted to improving the numbers of minorities in medicine, ideas and program information must be shared among institutions. In this spirit, we review our experience at Massachusetts General Hospital. We found that the first step toward this goal must be an institutional commitment based on increased awareness and on special effort focused on housestaff recruitment. Once the numbers of minorities increase, the department chairperson, training program directors, and other involved faculty can work with younger minority physicians; the cooperative relationship thus created can guide the development of a strong minority recruitment program without requiring an undue time commitment from minority trainees and faculty. The APM has a combined goal: to achieve early practical results in individual departments, to play a catalytic role with the community and other national medical organizations, and to increase the number of minorities entering medical school and careers in medicine generally. PMID- 1586127 TI - Simple modifications of the current curriculum to enhance educational experience. AB - Changes in medical practice and in the financing of hospital care have resulted in a narrowing spectrum of adult medical illness among hospitalized patients. Residency training based primarily in the hospital underemphasizes many diseases and disorders that are treated exclusively at ambulatory sites. Curriculum modifications should allow for increased training time for residents in the ambulatory care setting. Reducing clinical inpatient service demands on residents and alleviating the attendant stress will allow more time for such educational experiences. The Medical College of Virginia has had recent experience with three modifications to the curriculum, which are intended to accomplish these ends: a specialized unit for inpatient services, which is not staffed by interns; a reorganization of the daily inpatient care schedule; and a modified "night float" team. PMID- 1586128 TI - Integrating emerging disciplines. AB - The dynamics of medicine force us to continually update the content of residency curricula. Before selecting the material to be added or withdrawn from the curricula, goals for the desired product must be established. Further, the potential effects of emerging disciplines on the structure and composition of departments and residencies must be carefully considered. The Residency Review Committee for Internal Medicine (RRC-IM) is the principal instrument for forcing the integration of emerging disciplines into clinical education. Several questions must be considered when deciding how best to integrate these new disciplines. Should selected internists be designated to teach them? What are the most appropriate training sites? Which disciplines should be linked for pedagogic efficiency and relevance? How do we separate the educational pathways for generalists and subspecialists? The strategy of requiring additional training for a second certificate from the American Board of Internal Medicine (ABIM) has served internal medicine well for 50 years. Innovations in science and technology, however, are occurring at an accelerated pace. One solution may be to separate standardized residency training into multiple 4-year tracks that produce variously skilled graduates. PMID- 1586129 TI - Roles of various organizations in internal medicine curriculum reform. AB - The curriculum in internal medicine for medical students and residents is being driven increasingly by the service demands of our teaching hospitals and is badly in need of fundamental reform. In reasserting the primacy of education as the driving force for the curriculum, numerous tasks must be done to achieve successful reform. These tasks are well within the scope of the several organizations that command leadership positions in the discipline of internal medicine and that represent the spectrum of activities required to discharge the specialty's public responsibility. These organizations include the Association of Professors of Medicine (APM), the Association of Program Directors in Internal Medicine (APDIM), the Society of General Internal Medicine (SGIM), The Residency Review Committee for Internal Medicine (RRC-IM), the American Board of Internal Medicine (ABIM), the American College of Physicians (ACP), the American Society of Internal Medicine (ASIM), and the Federated Council of Internal Medicine (FCIM). The challenge posed by the need for curriculum reform is to rouse these organizations to concerted action. Each of the seven organizations must assume a specific role and a unique set of responsibilities in the epic reforms envisioned. PMID- 1586130 TI - Genetic polymorphism of human deoxyribonuclease II (DNase II): low activity levels in urine and leukocytes are due to an autosomal recessive allele. AB - The objectives of this study were to elucidate the genetic basis of human deoxyribonuclease II (DNase II) and to evaluate its usefulness as a genetic and/or diagnostic marker. We have devised a novel, specific and highly sensitive assay method for the urinary and leukocytic enzymes (Yasuda et al. 1991). The distribution of the activities of both enzymes displayed clear-cut bimodality and the Japanese study population could be classified into two distinct types, namely low-activity (DNASE2 L) and high-activity (DNASE2 H), which indicates the existence of a genetic polymorphism in the activity levels of urinary and leukocytic DNase IIs. Close correlations between the leukocytic and urinary enzyme activity levels from the same individuals were observed and the types in the leukocyte samples agreed with the types found in the corresponding urine samples. In a population study of 528 unrelated Japanese individuals, the gene frequencies of the low activity (DNASE2*L) and the high activity (DNASE2*H) alleles were calculated to be 0.632 and 0.368, respectively. The sex and age of individuals did not affect the distribution of DNase II activity levels. The family study results were compatible with the model that the low activity type is due to an autosomal recessive gene, which indicates that DNASE2 L represents homozygosity for DNASE2*L and DNASE2 H corresponds to homozygosity for DNASE2*H and heterozygosity for DNASE2*L and DNASE2*H. PMID- 1586131 TI - Genetic relationship between the 3'-VNTR and diallelic apolipoprotein B gene polymorphisms: haplotype analysis in individuals of European and south Asian origin. AB - The genetic relationship amongst apolipoprotein B (apo B) gene polymorphisms (signal peptide insertion/deletion (Leu-Ala-Leu-16/-14), XbaI (Thr2488), EcoRI (Glu4154----Lys), Asn4311----Ser, 3'-VNTR) has been investigated in samples of South Asian (Indian) and Swedish individuals. The frequency distribution of alleles at all these sites was found to be significantly different between the South Asian and the Swedish samples (deletion allele: 0.20 v. 0.31, X+ (presence of XbaI cutting site): 0.29 v. 0.55, R- (absence of EcoRI cutting site): 0.11 v. 0.19, Ser4311: 0.45 v. 0.19). The distribution of allele frequencies at the VNTR site was bimodal in both populations. However, in South Asians, the most common allele was a 35 repeat unit allele, whilst in the Swedish sample, and in all other reports from Caucasian samples the 37 repeat unit allele was the most frequent (South Asian v. Swedish: 35 allele: 0.36 v. 0.19, 37 allele: 0.25 v. 0.48). Furthermore, four new alleles at the apo B gene 3'-VNTR site (15, 17, 32, 38 repeat unit alleles) were observed in South Asians, of which two (15 and 17 repeat unit alleles) were well outside the bimodal distribution. In both samples, strong linkage disequilibrium and allelic association were detected between alleles at the 3'-VNTR and each of the other sites, and also between the ins/del and XbaI sites and between the XbaI and Asn4311----Ser sites. The same five common haplotypes as defined by ins/del, XbaI, EcoRI and Asn4311----Ser were found to be present in both samples comprising 97 and 99% of the haplotypes observed in the South Asian and Swedish samples respectively. Detailed analysis revealed the predominant occurrence of certain 3'-VNTR alleles on specific haplotypes and demonstrates the usefulness of the VNTR site for haplotyping and representative association studies. A model for the evolutionary relationship of the major haplotypes including the 3'-VNTR site is presented. These findings support a mechanism of replication slippage as a major factor for the generation of new alleles at the apo B 3'-VNTR locus rather than unequal crossing over. PMID- 1586132 TI - Kinetic properties of the common electrophoretic variants of human S adenosylhomocysteine hydrolase (AHCY): the effect of four nucleoside analogue inhibitors. AB - Red blood cell S-adenosylhomocysteine hydrolase (AHCY) from individuals of 1, 2-1 and 3-1 phenotypes was partially purified and Km and Vmax determined in the absence and in the presence of the following inhibitors: 3-deaza-adenosine (DZA), 3-deaza-aristeromycin (DZAry), 2-chloro adenosine (2-Cl-ado) and purine riboside (or nebularine). The three phenotypes 1, 2-1, 3-1 showed similar Km (32.58, 39.22 and 34.84 microM respectively), but the ratio Km/Vmax was statistically different. DZA and DZAry appeared to be strong competitive inhibitors. The AHCY 1 phenotype was more resistant to their action, while the 3-1 variant was more sensitive. 2-Cl-ado and purine riboside were weaker inhibitors; the type of inhibition varied among the three phenotypes, but, again, the AHCY 1 phenotype was less sensitive than the other two. PMID- 1586133 TI - The number of loci needed for ELOD calculations. AB - This theoretical approach to multiple markers considers the problem of a trait locus flanked by an arbitrary number of linked, ordered markers. Using the criterion of the Expected LOD score (ELOD) for mating, an algorithm is developed to specify the subset of markers required to provide the full linkage information available from a given parental genotype. PMID- 1586134 TI - Metrical Venn diagrams. AB - A type of Venn diagram is described which enables the observed frequencies in a 2x2x2 contingency table to be compared with their expectations on the hypothesis of no associations. PMID- 1586135 TI - Cytokine expression in the brain during the acquired immunodeficiency syndrome. AB - The pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin-1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV-seropositive and -seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin-1 and -6, tumor necrosis factor-alpha and -beta, and interferon gamma. Levels of soluble CD4, CD8, and interleukin-2 receptor, as well as interferon gamma, tumor necrosis factor-alpha, beta 2-microglobulin, neopterin, and interleukin-6 and -1 beta were assayed in the cerebrospinal fluid and plasma of many of these individuals during life. The HIV-seropositive group included individuals without neurological disease, those with CNS opportunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present on microglial cells, which were frequently positive for tumor necrosis factor-alpha. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin-1 and interferon gamma and less frequently for tumor necrosis factor and interleukin-6. There were gliosis and significant increases in MHC class II antigen, interleukin-1, and tumor necrosis factor-alpha in HIV-positive patients compared to HIV-negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, beta 2 microglobulin, and neopterin. There was no correlation in HIV-positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of "immune activation" in the brains of HIV-positive compared to HIV-negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy. PMID- 1586136 TI - Human immunodeficiency virus infection in microglia: correlation between cells infected in the brain and cells cultured from infectious brain tissue. AB - In acquired immunodeficiency syndrome, the lesions of the central nervous system in association with the human immunodeficiency virus are thought to be related to an infection of microglia, although no studies are available in which cultured and physiological characteristics of microglia cells infected in vivo have been examined. In this report, we used brain tissue from a child dying of human immunodeficiency virus infection and show that microglia cells were the main cell population being infected. Moreover, isolated macrophage-like cells from fresh brain material revealed a close resemblance to peripheral blood macrophages in their content of surface and intracellular antigens. No virus particles or viral antigens were produced by these cells during the first week of cultivation. Productive infection was readily apparent, however, by day 30. This finding illustrates the slow nature of the virus life cycle in these cells and the minimal cytopathology that accompanied the infection. PMID- 1586137 TI - Distribution of cisternal blood in patients with acute hydrocephalus after subarachnoid hemorrhage. AB - The distribution of cisternal blood in relation to the development of acute hydrocephalus was studied in 246 consecutive patients with aneurysmal subarachnoid hemorrhage who were admitted within 72 hours. Patients with evidence on the initial computed tomograph (CT) of subarachnoid hemorrhage caused by other than a ruptured aneurysm and patients with a negative angiography were excluded. Acute hydrocephalus (defined as a bicaudate index, measured on the initial CT or on a repeat CT within 1 week after subarachnoid hemorrhage, exceeding the 95th percentile for age) was found on the initial CT in 50 (20%) of the 246 patients and on a repeat CT in 9 other patients. Ventricular blood was found significantly more often in patients with acute hydrocephalus than in those in whom acute hydrocephalus did not develop (28 of 59 [47%] versus 58 of 187 [31%]; chi 2 = 4.634, p = 0.031). When the analysis was restricted to the 86 patients with ventricular blood, no significant differences were found in the total amount of cisternal blood and in the distribution of cisternal blood between patients with and without hydrocephalus. In contrast, among the 160 patients without ventricular blood, hydrocephalus was associated with a slightly higher total amount of cisternal blood (Wilcoxon's rank sum test, p = 0.023), and significantly more patients with acute hydrocephalus had a higher score in both ambient cisterns than patients without acute hydrocephalus (20 of 31 [65%] versus 41 of 129 [32%]; chi 2 = 10.007, p = 0.002).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586138 TI - Bilateral striopallidodentate calcinosis: cerebrospinal fluid, imaging, and electrophysiological studies. AB - We report the genetic, clinical, electrophysiological, and imaging studies in a family with bilateral striopallidodentate calcinosis (Fahr's disease). The intracerebral calcium deposits occurred before onset of the symptoms in the third decade of life. Progressive neurological deterioration occurred in the fifth decade of life in the proband. Cerebrospinal fluid homocarnosine, a central nervous system-specific peptide, was increased twofold in patients with autosomal dominant bilateral stripallidodentate calcinosis; in sporadic cases, there was no detectable homocarnosine and a decreased level of histidine. With advancing age, the amount of calcification increases, but it has not been determined if a critical amount must be reached before symptoms occur. Computerized tomography is superior to magnetic resonance imaging for radiological diagnosis. Despite diffuse striatal calcification, striatal 6-[18F]fluoro-L-dopa uptake did not reveal any difference between patients and control subjects, from which we infer persisting integrity of the nigrostriatal dopaminergic pathway. PMID- 1586139 TI - Experimental conduction block induced by serum from a patient with anti-GM1 antibodies. AB - Increased titers of antibodies to GM1 ganglioside in humans are associated with lower motor neuron disease and predominantly motor neuropathy with or without conduction block. To investigate the possible mechanism of these antibodies, we injected the serum of a patient with anti-GM1 antibodies who had motor neuron disease and multifocal motor conduction block, into rat sciatic nerve. When injected with fresh human complement, the serum-induced conduction block with temporal dispersion and deposits of immunoglobulin were detected at the nodes of Ranvier. Electron microscopic studies revealed demyelination in 6.5% of the fibers. After preabsorption with GM1, the serum had no effect, suggesting that the anti-GM1 antibodies were responsible for the conduction abnormalities. PMID- 1586140 TI - MELAS: clinical features, biochemistry, and molecular genetics. AB - We studied 23 patients with clinically defined mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), 25 oligosymptomatic or asymptomatic maternal relatives, and 50 mitochondrial disease control subjects for the presence of a previously reported heteroplasmic point mutation at nt 3,243 in the transfer RNA(Leu(UUR)) gene of mitochondrial DNA. We found a high concordance between clinical diagnosis of MELAS and transfer RNA(Leu(UUR)) mutation, which was present in 21 of the 23 patients with MELAS, all 11 oligosymptomatic and 12 of 14 asymptomatic relatives, but in only five of 50 patients without MELAS. The proportion of mutant genomes in muscle ranged from 56 to 95% and was significantly higher in the patients with MELAS than in their oligosymptomatic or asymptomatic relatives. In subjects in whom both muscle and blood were studied, the percentage of mutations was significantly lower in blood and was not detected in three of 12 asymptomatic relatives. The activities of complexes I + III, II + III, and IV were decreased in muscle biopsies harboring the mutation, but there was no clear correlation between percentage of mutant mitochondrial DNAs and severity of the biochemical defect. PMID- 1586141 TI - Wallenberg's syndrome: lateropulsion, cyclorotation, and subjective visual vertical in thirty-six patients. AB - We measured the subjective visual vertical, cyclorotation of the eyes, and head and body lateropulsion in 36 patients with Wallenberg's syndrome. All patients exhibited significant tilts of the internal representation of the gravity vector, as indicated by deviation of subjective visual vertical ipsiversive to the lesion. Most patients (82%) had ipsiversive cyclorotation of one or both eyes, especially excyclotropia of the eye ipsilateral to the brainstem lesion. Twelve of 36 patients (33%), those with the most severe body lateropulsion, had a complete ocular tilt reaction consisting of head tilt, skew deviation, and cyclorotation in the roll plane. We hypothesize that deviation of subjective visual vertical, lateropulsion of the body, and cyclorotation of the eyes are the perceptual, the ocular motor, and the postural consequences of a common lesion of central vestibular pathways that subserve the vestibuloocular reflex in the roll plane. Lateropulsion in patients with Wallenberg's syndrome is interpreted as a postural consequence of an abnormal tilt of the internal representation of orientation in space. PMID- 1586142 TI - Voluntary activation and fiber density of fasciculations in motor neuron disease. AB - Two hundred voluntarily activated motor units and 211 fasciculations were recorded in the biceps of 10 patients with motor neuron disease with the Macro EMG technique. Twenty-two fasciculations, in nine of 10 muscles, had a potential of closely similar shape, amplitude, and area to that of a voluntary unit. Fasciculating units that could not be activated voluntarily had a higher mean number of spikes in their triggering single fiber potentials than units that could only be activated voluntarily, but statistically similar Macro EMG parameters. The mean number of single fiber spikes, and Macro EMG parameters, of fasciculations activated voluntarily, were similar to those of units that were only activated voluntarily. A positive correlation between fiber density and Macro EMG median amplitude and area in individual patients, and between number of single fiber spikes and Macro EMG amplitudes and areas in the pooled data, was found for fasciculations but not for voluntary units. At least 10% of fasciculations in patients with motor neuron disease may originate near or above the point of axonal branching and a proportion of those without evidence of voluntary activation may have a higher number of smaller muscle fibers, or more closely packed muscle fibers, of similar or greater size, than voluntarily activated motor units. Differences in the peripheral microanatomy of a number of fasciculation units not activated voluntarily may underlie ectopic impulse generation in the terminal axonal arborization, endplate zone, or muscle fibers of these units. PMID- 1586143 TI - Suspected low-grade glioma: is deferring treatment safe? AB - Deferring therapeutic intervention may worsen outcome in patients with low-grade glioma. To address this issue, we searched our records and located 26 patients who presented with a transient event (most often seizures), who had radiographic evidence strongly suggestive of a low-grade primary supratentorial neoplasm, and for whom all therapy (except anticonvulsants) was withheld until deemed necessary (WAIT Group). For comparison, 20 patients who presented similarly, but for whom immediate intervention was elected, served as a comparison group (NOWAIT Group). Fifteen patients in the WAIT Group required eventual surgery or radiation therapy at intervals ranging from 4 to 123 months (median, 29 months) between radiographic diagnosis and therapeutic intervention; reasons for such intervention included increasing tumor size, uncontrollable seizures, or malignant transformation of tumor. At surgery, there was an increased number of anaplastic tumors noted in the patients in the WAIT Group (p less than 0.02); nevertheless, if the rate of malignant transformation was examined from time of diagnosis, no differences were noted between the patients in the two groups. Similarly, no difference in survival or quality of life could be demonstrated from time of radiographic diagnosis. Therefore, we could not demonstrate that deferring therapy worsens outcome for these patients. PMID- 1586144 TI - Low-grade gliomas: when to treat? PMID- 1586145 TI - Motor nerve biopsy in severe Guillain-Barre syndrome. AB - We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain-Barre syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally identified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain-Barre syndrome. PMID- 1586146 TI - Cerebrospinal fluid amino acids in amyotrophic lateral sclerosis. PMID- 1586147 TI - The therapeutic effect of bromocriptine on acute and chronic experimental allergic encephalomyelitis. PMID- 1586148 TI - Brain 31P-magnetic resonance spectroscopy in mitochondrial cytopathies. PMID- 1586149 TI - Biosynthesis of bikunin (urinary trypsin inhibitor) in rat hepatocytes. AB - One of the major sulfated proteins secreted by rat hepatocytes contains a low sulfated chondroitin sulfate chain and its apparent molecular mass upon sodium dodecyl sulfate/polyacrylamide gel electrophoresis shifts from 40 to 28 kDa upon chondroitinase ABC treatment (E. M. Sjoberg and E. Fries, 1990, Biochem. J. 272, 113-118). These properties suggest that this protein is the rat homologue of the major trypsin inhibitor of human urine which was recently named bikunin. In serum, bikunin occurs mainly as a subunit of the pre-alpha-inhibitor and the inter-alpha-inhibitor; in these proteins it is covalently linked to the other polypeptides through its chondroitin sulfate chain. Bikunin has been shown to be synthesized by liver cells as a 42-kDa precursor, in which it is linked to alpha 1-microglobulin by two basic amino acids. We have isolated bikunin from rat urine and prepared antibodies against it. In rat hepatocytes pulse-labeled with [35S]methionine, these antibodies precipitated a labeled protein of 42 kDa. Upon chase, three different labeled proteins were recognized by the antibodies in the medium: one protein of 40 kDa (free bikunin), one of 125 kDa (presumably pre alpha-inhibitor), and one greater than 240 kDa (possibly a protein related to the inter-alpha-inhibitor). Pulse-chase experiments with [35S]sulfate showed that these proteins occurred intracellularly as precursors containing alpha 1 microglobulin. These results demonstrate that the completion of the chondroitin sulfate chain and its coupling to other polypeptide chains occur before the cleavage of the alpha 1-microglobulin/bikunin precursor. PMID- 1586150 TI - Role of cytosolic NAD(P)H-quinone oxidoreductase and alcohol dehydrogenase in the reduction of p-nitrosophenol following chronic ethanol ingestion. AB - Rats fed an ethanol-containing diet for 4 weeks showed a 3- to 5-fold increase over isocalorically pair-fed controls with respect to cytosolic NAD(P)H-quinone oxidoreductase (NQOR) (E.C.1.6.99.2) with both menadione and dichlorophenol indophenol as substrates. Rates of NAD(P)H-dependent p-nitrosophenol (pNSP) reduction catalyzed by rat liver cytosolic fractions were increased 1.5- to 2 fold upon pretreatment of the animal with ethanol. NQOR contributed almost exclusively to the NADPH-dependent C-nitrosoreductase activity in cytosol as judged by the strong inhibition of the reaction by dicoumarol. In contrast, NADH dependent C-nitrosoreductase activity was inhibited 70-80% by pyrazole and thus may be attributed mainly to alcohol dehydrogenase(s). Highly purified rat liver cytosolic NQOR catalyzed the NADH- and NADPH-dependent reduction of pNSP to p aminophenol. We therefore suggest that ethanol ingestion enhances the reduction of the C-nitrosoaromatics formed upon cytosolic metabolism of arylamines or nitroarenes by two mechanisms. Increased NADPH-dependent reduction is mediated by the induction of cytosolic NQOR while an NADH-dependent pathway responds to the increased availability of reduced cofactor upon ethanol ingestion and involves mainly the alcohol dehydrogenase-mediated reduction of such compounds. PMID- 1586151 TI - Distribution and redox state of ubiquinones in rat and human tissues. AB - The distribution and redox state of ubiquinone in rat and human tissues have been investigated. A rapid extraction procedure and direct injection onto HPLC were employed. It was found in model experiments that in postmortem tissue neither oxidation nor reduction of ubiquinone occurs. In rat the highest concentrations of ubiquinone-9 were found in the heart, kidney, and liver (130-200 micrograms/g). In brain, spleen, and intestine one-third and in other tissues 10 20% of the total ubiquinone contained 10 isoprene units. In human tissues ubiquinone-10 was also present at highest concentrations in heart, kidney, and liver (60-110 micrograms/g), and in all tissues 2-5% of the total ubiquinone contained 9 isoprene units. High levels of reduction, 70-100%, could be observed in human tissues, with the exception of brain and lung. The extent of reduction displayed a similar pattern in rat, but was generally lower. PMID- 1586152 TI - Overexpression of plant histidinol dehydrogenase using a baculovirus expression vector system. AB - A cDNA encoding cabbage histidinol dehydrogenase, including the chloroplast transit peptide sequence, was overexpressed using a baculovirus expression vector system. The maximum level of the expression of histidinol dehydrogenase was reached 5 days after infection of the insect cells. Two forms of recombinant histidinol dehydrogenase with molecular masses of 53 and 52 kDa, respectively, were obtained by a one-step purification from the cell homogenate. Compared with the 52-kDa form, the 53-kDa form contained 10 additional amino acids at the N terminus derived from the transit peptide. By incubating the cell homogenate for 2 h at 30 degrees C, the 53-kDa form could be completely converted to the 52-kDa form. This conversion was blocked by leupeptin. Eighty percent of the converted 52-kDa form had Cys at position 31 at the N-terminal amino acid and the rest had Met 33. Kinetic properties of the recombinant enzyme were virtually identical to those of histidinol dehydrogenase isolated from cabbage plants. The overexpression of recombinant cabbage histidinol dehydrogenase in insect cells, the proteolytic processing of the preprotein next to the N-terminus (compared to the mature cabbage enzyme), and its easy purification allow the preparation of large amounts of the active enzyme for structural and functional studies. PMID- 1586153 TI - Effects of deferrioxamine on iron-catalyzed lipid peroxidation. AB - The kinetics of iron binding by deferrioxamine B mesylate and the ramifications of this process upon iron-catalyzed lipid peroxidation were assessed. The relative rates of Fe(III) binding by deferrioxamine varied for the chelators tested as follows: ADP greater than AMP greater than citrate greater than histidine greater than EDTA. The addition of a fivefold molar excess of deferrioxamine to that of Fe(III) did not result in complete binding (within 10 min) for any of the Fe(III) chelates tested except ADP:Fe(III). The rates of Fe(III) binding by deferrioxamine were greater at lower pH and when the competing chelator concentration was high in relationship to iron. The relatively slow binding of Fe(III) by deferrioxamine also affected lipid peroxidation, an iron dependent process. The addition of deferrioxamine to an ascorbate- and ADP:Fe(III)-dependent lipid peroxidation system resulted in a time-dependent inhibition or stimulation of malondialdehyde formation (i.e., lipid peroxidation), depending on the ratio of deferrioxamine to iron. Converse to Fe(III), the rates of Fe(II) binding by deferrioxamine from the chelators tested above were rapid and complete (within 1 min), and resulted in the oxidation of Fe(II) to Fe(III). Lipid peroxidation dependent on Fe(II) autoxidation was stimulated by the addition of deferrioxamine. Malondialdehyde formation in this system was inhibited by the addition of catalase, and a similar extent of lipid peroxidation was achieved by substituting hydrogen peroxide for deferrioxamine. Collectively, these results suggest that the kinetics of Fe(III) binding by deferrioxamine is a slow, variable process, whereas Fe(II) binding is considerably faster. The binding of either valence of iron by deferrioxamine may result in variable effects on iron-catalyzed processes, such as lipid peroxidation, either via slow binding of Fe(III) or the rapid binding of Fe(II) with concomitant Fe(II) oxidation. PMID- 1586155 TI - Isotypes of protein kinase C in bovine sperm. AB - Protein kinase C is present in bovine epididymal sperm. The enzyme was partially purified by gel filtration on Sephacryl S-300. The Ca2+/phosphatidylserine dependent histone phosphotransferase activity elutes from the gel filtration column in a manner corresponding to a Mr approximately 80 kDa. The activity peak also corresponds with [3H]phorbol 12,13-dibutyrate binding activity. Immunoblot analysis of the partially purified enzyme with isozyme-specific monoclonal antibodies revealed the presence of alpha-, beta-, and gamma-subspecies of protein kinase C. Indirect immunofluorescence showed that the antibodies against alpha-, beta-, and gamma-subspecies produced prominent staining of the postacrosomal region of the sperm head. In addition, beta-subspecies antibodies produced minor staining of the midpiece and gamma-subspecies antibodies produced a minor staining of the acrosomal region. PMID- 1586154 TI - Regulation of the malic enzyme and fatty acid synthase genes in chick embryo hepatocytes in culture: corticosterone and carnitine regulate responsiveness to triiodothyronine. AB - Triiodothyronine (T3) added to chick embryo hepatocytes between 20 and 68 h of culture caused a 30- to 40-fold increase in malic enzyme activity. This T3 response decreased as a function of time; after 1 week in culture, a 48-h incubation with T3 had no effect on hepatocyte malic enzyme activity. Neither corticosterone nor carnitine had a significant effect on malic enzyme activity in the absence of T3 at any time or on the response of malic enzyme to T3 during the first 68 h of culture; both stimulated responsiveness to T3 subsequent to 68 h. The effects of corticosterone and carnitine on malic enzyme activity were additive, suggesting different mechanisms. Corticosterone and carnitine regulated abundance of malic enzyme mRNA. For corticosterone, at least, this effect was due to regulation of transcription. Abundance of fatty acid synthase mRNA was also stimulated by T3 in chick embryo hepatocytes in culture, and its responsiveness to T3 decreased with time. Corticosterone and carnitine stimulated responsiveness to T3 at times subsequent to 68 h. Corticosterone had no effect on binding of T3 to nuclear receptors. Intracellular accumulation of long-chain fatty acids or long-chain acyl-CoAs probably did not cause the loss of responsiveness to T3 or the stimulation of that responsiveness by corticosterone or carnitine because adding serum albumin (0.5%) or long-chain fatty acids (0.25-0.5 mM) to the medium was without effect. Corticosterone and carnitine may control the levels of other metabolic intermediates or protein factors which, in turn, regulate the transcriptional response of the lipogenic genes to T3. PMID- 1586156 TI - A molecular and biochemical analysis of the structure of the cyanogenic beta glucosidase (linamarase) from cassava (Manihot esculenta Cranz). AB - The cyanogenic beta-glucosidase (linamarase) of cassava is responsible for the first step in the sequential break-down of two related cyanoglucosides. Hydrolysis of these cyanoglucosides occurs following tissue damage and leads to the production of hydrocyanic acid. This mechanism is widely regarded as a defense mechanism against predation. A linamarase cDNA clone (pCAS5) was isolated from a cotyledon cDNA library using a white clover beta-glucosidase heterologous probe. The nucleotide and derived amino acid sequence is reported and five putative N-asparagine glycosylation sites are identified. Concanavalin A affinity chromatography and endoglycosidase H digestion demonstrate that linamarase from cassava is glycosylated, having high-mannose-type N-asparagine-linked oligosaccharides. Consistent with this structure and the extracellular location of the active enzyme is the identification of an N-terminal signal peptide on the deduced amino acid sequence of pCAS5. PMID- 1586157 TI - Purification and characterization of dipeptidyl peptidase I from human spleen. AB - The lysosomal hydrolase, dipeptidyl peptidase I (DPPI), was purified from human spleen and its enzymatic activity characterized. The enzyme was purified to apparent homogeneity by a combination of differential pH solubility, heat treatment, affinity chromatography on concanavalin A-agarose and p hydroxymercuribenzoate-agarose, and gel filtration chromatography on Sephacryl S 300. This procedure resulted in a 1100-fold purification of DPPI protein with a yield of approximately 2% of the total DPPI activity. The enzyme was characterized as a glycoprotein with a pI of 5.4, a molecular mass of 200,000 Da as determined by gel filtration under nondenaturing conditions, and a subunit size of 24,000 Da. Amino acid sequence analysis of peptides isolated from cyanogen bromide and trypsin digests of the 24,000-Da subunit revealed extensive sequence similarity between human and rat DPPI. Purified DPPI exhibited both hydrolytic and transpeptidase (polymerase) activity. DPPI exhibited activity against a variety of dipeptide substrates including peptides with either non polar or polar residues in the P1 position. In contrast to the reported substrate specificity of bovine and murine DPPI, the human enzyme exhibited a modest preference for peptides with nonpolar residues in the P1 position. DPPI content was found to be highest among cytotoxic lymphocytes and myeloid cells. The high level of DPPI expression in these cell populations correlates with their sensitivity to the toxic effects of leucyl-leucine methyl ester, a substrate for DPPI. PMID- 1586158 TI - Specific and nonspecific interactions of integration host factor with oligo DNAs as revealed by circular dichroism spectroscopy and filter binding assay. AB - Binding specificity of integration host factor (IHF) to oligo DNAs has been studied by circular dichroism (CD) spectroscopy and filter binding experiment. CD difference spectra of IHF-DNA complexes demonstrated that a conformational change in DNA was induced by binding of IHF when DNA had a consensus sequence for the binding sites of IHF, but that such conformational change was not observed for consensus DNA 20 mer as well as nonconsensus DNA 45 mer. Dissociation constants for IHF-DNA complexes determined by filter binding assay showed that IHF has indeed stronger affinity to DNA with the consensus binding site than to nonconsensus DNA, but the difference in its affinity between consensus and nonconsensus DNAs was rather small, 3.4-fold. It was, therefore, concluded that the flanking regions of the consensus sequence are important for the specific binding of IHF and that its binding specificity is well characterized by the induced conformational change in DNA rather than by dissociation constants for IHF-DNA complexes. PMID- 1586159 TI - Bactericidal effect of Fe2+, ceruloplasmin, and phosphate. AB - Fe2+, when combined with ceruloplasmin or phosphate, was bactericidal to Escherichia coli at pH 5.0, and when Fe2+, ceruloplasmin, and phosphate were combined, a bactericidal effect was observed under conditions, i.e., short incubation period, in which Fe2+ plus ceruloplasmin and Fe2+ plus phosphate were ineffective. Bactericidal activity increased with the ceruloplasmin or phosphate concentration to a maximum and then decreased as their concentration was further increased. Fe2+ was oxidized in the presence of ceruloplasmin, phosphate, or, in particular, a combination of the two. A bactericidal effect was observed when there was only a partial loss of Fe2+, with more extensive oxidation resulting in a loss of bactericidal activity. The bactericidal effect of Fe2+ plus ceruloplasmin and/or phosphate was unaffected by catalase or superoxide dismutase and was not associated with iodination. Fe-EDTA was also bactericidal at an Fe2+: EDTA molar ratio of 1:0.5, where Fe2+ was partially oxidized. However, in contrast to Fe2+ plus ceruloplasmin and/or phosphate, bactericidal activity was inhibited by catalase and was associated with iodination. Combinations of Fe2+ and Fe3+ were not bactericidal under the conditions employed. A requirement for Fe2+ plus either a product of Fe2+ oxidation or an iron ceruloplasmin and/or phosphate chelate for bactericidal activity is proposed. PMID- 1586160 TI - Biosynthesis of lipophosphoglycan from Leishmania donovani: characterization of mannosylphosphate transfer in vitro. AB - Lipophosphoglycan (LPG) is the major surface glycoconjugate of Leishmania donovani promastigotes and is composed of a capped polymer of repeating PO4 6Gal(beta 1,4)Man alpha 1 disaccharide units linked via a phosphosaccharide core to a lyso-1-O-alkylphosphatidylinositol anchor. An exogenous acceptor composed of the glycolipid anchor portion of LPG was shown to stimulate the enzymatic synthesis of the repeating phosphorylated disaccharide units of LPG in a cell free system. Using the exogenous acceptor, GDP-[3H]Man, [beta-32P]GDP-Man, and unlabeled UDP-Gal as substrates, membrane preparations from an LPG-defective mutant of L. donovani that lacks endogenous acceptors catalyzed the incorporation of the doubly labeled mannosylphosphate unit into a product that exhibited the chemical and chromatographic characteristics of LPG. Analysis of fragments generated by mild acid hydrolysis of the radiolabeled product indicated that [3H]mannose-1-[32P]PO4 had been transferred from the dual-labeled sugar nucleotide. These results are consistent with the proposal that the repeating units of the L. donovani LPG are synthesized by the alternating transfer of mannose 1-phosphate and galactose from their respective nucleotide donors. PMID- 1586161 TI - Purification and characterization of an unusually large fatty acid synthase from Mycobacterium tuberculosis var. bovis BCG. AB - Fatty acid synthase was purified from Mycobacterium tuberculosis var. bovis BCG. The method developed gave a 23% yield of the synthase and also yielded purified mycocerosic acid synthase. The fatty acid synthase is of unusually large size and composed of two 500-kDa monomers. The amino acid composition of the two synthases was not identical; the N-terminus of the fatty acid synthase was blocked, whereas that of the mycocerosic acid synthase was not. Western blot analysis of crude mycobacterial extracts with polyclonal antibodies prepared against each synthase showed a single band in each case with no cross-reactivity with the other synthase. Fatty acid synthase required both NADH (Km, 11 microM) and NADPH (Km, 14 microM). The Km for acetyl-CoA and malonyl-CoA were 5 and 6 microM, respectively. Fatty acids were released from the synthase as CoA esters. A bimodal distribution of fatty acids was obtained at around C16 and C26. The primer utilization also reflects the de novo synthesis and elongation capabilities of the enzyme; acetyl-CoA was the preferred primer but CoA esters up to C8 but not C12 and C14 could serve as primers, whereas C16 was readily used as a primer for elongation. Addition of CoA and CoA ester-binding oligosaccharides caused enhanced release of C16. Since this mycobacterial fatty acid synthase is twice as large as other multifunctional fatty acid synthases, it is tempting to suggest that this synthase represents a head to tail fusion of two fatty acid synthase genes coding for a double size protein with one-half producing C16 acid and the other elongating the C16 acid to a C26 acid. The monomer of fatty acid synthase from M. smegmatis was immunologically similar and equal in size to the synthase from M. tuberculosis. PMID- 1586162 TI - Modulation of tubulin-nucleotide interactions by metal ions: comparison of beryllium with magnesium and initial studies with other cations. AB - With microtubule-associated proteins (MAPs) BeSO4 and MgSO4 stimulated tubulin polymerization as compared to a reaction mixture without exogenously added metal ion, while beryllium fluoride had no effect (E. Hamel et al., 1991, Arch. Biochem. Biophys. 286, 57-69). Effects of both cations were most dramatic at GTP concentrations in the same molar range as the tubulin concentration. We have now compared effects of beryllium and magnesium on tubulin-nucleotide interactions in both unpolymerized tubulin and in polymer. Polymer formed with magnesium had properties similar to those of polymer formed without exogenous cation, except for a 20% lower stoichiometry of exogenous GTP incorporated into the latter. In both polymers the incorporated GTP was hydrolyzed to GDP. Stoichiometry of GTP incorporation into polymers formed with beryllium or magnesium was identical, but much of the GTP in the beryllium polymer was not hydrolyzed. The beryllium polymer was more stable than the magnesium polymer. Beryllium also differed from magnesium in only weakly enhancing the binding of GTP in the exchangeable site of unpolymerized tubulin, while neither cation affected GDP exchange at the site. If both cations were present in a reaction mixture, polymer stability was little changed from that of the beryllium polymer, but most of the GTP incorporated into polymer was hydrolyzed. Six additional metal salts (AlCl3, CdCl2, CoCl2, MnCl2, SnCl2, and ZnCl2) also stimulated MAP-dependent tubulin polymerization, but enhanced polymer stability did not correlate with polymer GTP content. We postulate that enhanced polymer stability is a consequence of cation binding directly to tubulin and/or polymer while deficient GTP hydrolysis in the presence of beryllium, as well as aluminum and tin, is a consequence of tight binding of cation to GTP in the exchangeable site. PMID- 1586163 TI - Ultrastructural and biochemical characterization of a Synechocystis 6803 mutant with inactivated psbA genes. AB - A constructed Synechocystis 6803 mutant with a deletion of the three psbA genes was subjected to ultrastructural and biochemical characterization. This D1 depleted mutant also lacks the D2 protein and the chlorophyll a-binding protein CP-47. A general ultrastructural comparison between the wild type and the mutant did not reveal any major changes in cell appearance. We found by freeze-fracture analysis that approximately 60% of the endoplasmic face particles found in the wild-type thylakoids were missing in the mutant. A corresponding increase in protoplasmic face particles in the mutant thylakoids may represent a subcomplex of those photosystem II (PS II) polypeptides which accumulate in the absence of the D1 protein. Correlation of the PS I:PS II ratio with freeze-fracture data indicates that there is only one reaction center in each PS II freeze-fracture particle. Fluorescence measurements show that the CP-43 polypeptide in the mutant binds chlorophyll and that it may be connected to the phycobilisomes. Excitation energy can be transferred from the phycobilisomes to photosystem I in the absence of the photosystem II reaction center heterodimer and CP-47. This suggests that exciton transfer to photosystem I is mediated either directly by a terminal phycobilisome transmitter or via CP-43. PMID- 1586164 TI - Restoration of malonyl-CoA sensitivity of soluble rat liver mitochondria carnitine palmitoyltransferase by reconstitution with a partially purified malonyl-CoA binding protein. AB - Solubilization of rat liver mitochondria in 5% Triton X-100 followed by chromatography on a hydroxylapatite column resulted in the identification of malonyl-CoA binding protein(s) distinct from a major carnitine palmitoyltransferase activity peak. Further purification of the malonyl-CoA binding protein(s) on an acyl-CoA affinity column followed by sodium dodecyl sulfate gel electrophoresis indicated proteins with Mr mass of 90 and 45-33 kDa. A purified liver malonyl-CoA binding fraction, which was devoid of carnitine palmitoyltransferase, and a soluble malonyl-CoA-insensitive carnitine palmitoyltransferase were reconstituted by dialysis in a liposome system. The enzyme activity in the reconstituted system was decreased by 50% in the presence of 100 microM malonyl-CoA. Rat liver mitochondria carnitine palmitoyltransferase may be composed of an easily dissociable catalytic unit and a malonyl-CoA sensitivity conferring regulatory component. PMID- 1586165 TI - Purification and characterization of PSP-I and PSP-II, two major proteins from porcine seminal plasma. AB - Two major glycoproteins, designated PSP-I and PSP-II, were purified from porcine seminal plasma by ammonium sulfate fractionation, CM-cellulose chromatography, gel filtration on Sephadex G-75 (superfine), and reverse phase high performance liquid chromatography. These two proteins exist in several forms differing mainly in the carbohydrate moiety. The complete amino acid sequence of PSP-I has been determined by automated Edman degradation of peptides generated by proteolytic digestion and cyanogen bromide cleavage. The protein is 109 residues long and has a single glycosylation site at the asparagine residue at position 47. In addition, the N-terminal sequence of PSP-II has also been determined. PSP-I is a unique protein; a sequence homology search using the protein data base did not reveal any significant homology with other proteins. PSP-II shares 50% sequence homology with a family of zona pellucida-binding glycoproteins at the N-terminus. PMID- 1586167 TI - Ascorbic acid and transforming growth factor-beta 1 increase collagen biosynthesis via different mechanisms: coordinate regulation of pro alpha 1(I) and Pro alpha 1(III) collagens. AB - The specific mechanisms of collagen induction in human dermal fibroblasts by ascorbic acid and transforming growth factor-beta 1 (TGF-beta 1) and their effect in combination are uncertain. Collagen synthesis and steady-state levels of pro alpha 1(I) and pro alpha 1(III) collagen RNA were examined in human dermal fibroblasts treated with 100 microM ascorbic acid, 2.5 ng/ml TGF-beta 1, or both. Within 72 h ascorbic acid and TGF-beta 1 had increased collagen synthesis by 2.55 +/- 0.32- and 1.98 +/- 0.13-fold, respectively; in the presence of both, collagen synthesis increased 4.51 +/- 0.74-fold, appearing additive. Ascorbic acid acts specifically by increasing relative collagen synthesis whereas TGF-beta 1 increases overall protein synthesis. Steady-state levels of the pro alpha 1(I) collagen (5.8 and 4.8 kb) and pro alpha 1(III) collagen (5.4 and 4.8 kb) mRNAs were examined independently. Under each condition the steady-state levels of the longer transcripts for pro alpha 1(I) and pro alpha 1(III) collagens appeared coordinately and preferentially elevated. In the presence of both ascorbic acid and TGF-beta 1 the steady-state RNA levels did not increase in an additive manner, suggesting that the additive increase in collagen synthesis results from additional post-transcriptional mechanisms. PMID- 1586166 TI - The first 22 base pairs of the proximal promoter of the rat class I alcohol dehydrogenase gene is bipartite and interacts with multiple DNA-binding proteins. AB - The rat class I alcohol dehydrogenase (ADH) gene is primarily expressed in the liver. We previously showed that the liver-enriched transcription factor, the CCAAT/enhancer binding protein (C/EBP), binds to the proximal promoter of the rat class I ADH gene between positions -11 and -22 relative to the start site of transcription. We now demonstrate that another transcription factor, the liver activator protein (LAP), also interacts with the same region of the promoter based on the following observations: (1) LAP synthesized by in vitro transcription and translation of cloned cDNA sequence forms complexes with an oligonucleotide containing the C/EBP-binding sequence within the ADH promoter as determined by the electrophoretic mobility shift assay (EMSA), (2) purified LAP interacts with the proximal ADH promoter when analyzed by the DNase I protection assay, and (3) an ADH promoter-reporter gene construct containing the C/EBP binding site is transactivated by an eukaryotic expression vector containing the LAP sequence. EMSA of an oligonucleotide containing the first 22 base pairs (between positions -1 and -22) of the ADH promoter with rat liver nuclear extracts (RLNE) resulted in the formation of two major complexes. Complex 1 was competed away by a heterologous oligonucleotide containing a C/EBP-binding site within the promoter of the adipocyte 422 (aP2) gene, while complex 2 was not. Additional competition experiments with the ADH or 422 (aP2) oligonucleotide using either RLNE or extracts from 3T3-L1 adipocytes demonstrated that complex 1 contains either C/EBP or LAP, while complex 2 contains a DNA-binding protein that binds to a novel sequence 5'-TGGCCCAGTT-3' between positions -1 and -10 of the ADH promoter. Ultraviolet cross-linking between RLNE and a labeled oligonucleotide containing the above sequence indicates that this protein, designated EDBP (for enhancer-site downstream binding protein), has an estimated molecular weight of 47 kDa, which is larger than that reported for either C/EBP (42 kDa) or LAP (36 kDa). PMID- 1586168 TI - Antioxidant effect of Ebselen (PZ 51): peroxidase mimetic activity on phospholipid and cholesterol hydroperoxides vs free radical scavenger activity. AB - The selenocompound Ebselen (PZ 51) is a potent inhibitor of lipid peroxidation. This antioxidant effect has been previously attributed both to a peroxidase mimetic activity and to a free radical scavenging capability. In the present paper the latter is ruled out by competition kinetic analysis based on the inhibition of carotenoid bleaching by hydroperoxyl radicals. Furthermore, evidence is reported indicating that Ebselen exhibits a peroxidase activity extended to cholesterol and cholesterol ester hydroperoxides, besides phospholipid hydroperoxides. According to this, we propose that the unique mechanism of the antioxidant capacity of Ebselen is the reduction of lipid hydroperoxides present in liposomes or lipoproteins, eventually leading to the prevention of hydroperoxide-dependent peroxidation. PMID- 1586169 TI - Isopentenoid synthesis in embryonic Drosophila cells: prenylated protein profile and prenyl group usage. AB - It has been established that vertebrates and yeasts modified a unique subset of polypeptides with farnesyl and geranylgeranyl residues. This observation has been extended to Drosophila Kc cells. [3H]Mevalonate was incorporated into 54 Kc cell peptides (18-92 kDa). As reported for mammalian cells, most of the labeled peptides had molecular weights between 21 and 27 kDa. C18 radio-HPLC tryptic digest profiles for delipidized, [3H]mevalonate-labeled (a) insect (Drosophila and Spodoptera frugiperda) and mammalian (Chinese hamster ovary met 18-2b) cells, (b) Kc cell nuclear lamin, and (c) a 23.5-kDa purified Kc cell GTP-binding protein were compared and analyzed. [35S]Cysteine-labeled Kc cells yielded a tryptic digest radio-HPLC profile which was congruent with that for [3H]mevalonate-labeled cells. A significant fraction (30-33%) of the doubly labeled tryptic peptides were eluted with greater than or equal to 93% acetonitrile. Kc cell nuclear lamin tryptic digests yielded a single 3H-labeled product which migrated as S-farnesylcysteine. The Kc cell 23.5-kDa GTP-binding protein's 3H-labeled oligopeptide(s)/amino acid(s) was geranylgeranylated and its tryptic digest profile was representative of prenylated proteins whose oligopeptides eluted with greater than or equal to 93% acetonitrile. Moreover, the 3H-labeled oligopeptide/amino acid profiles plus prenyl group patterns for [3H]mevalonate-labeled Kc and mammalian cell total extracts were similar. Collectively, these observations supported a prenylated protein spectrum and prenyl group usage as highly conserved eukaryotic cellular characteristics. PMID- 1586170 TI - Effects of active site modification and reversible dissociation on the secondary structure of triosephosphate isomerase. AB - Binding of ligands to the catalytic center of mammalian triosephosphate isomerase (TPI) induces a conformational change(s) that enhances the specific deamidation of Asn71 at the subunit interface. Deamidation initiates dissociation and degradation of the enzyme in vivo and in vitro. We have utilized circular dichroism spectroscopy to examine the conformational changes in the enzyme upon ligand binding and subunit dissociation/reassociation. Native TPI from rabbit, chicken, and yeast exhibit similar spectra at pH 7.5, but are substantially different at pH 9.5. Covalent reaction of the active site Glu 165 with the substrate analogue 3-chloroacetol phosphate results in a conformational change (decrease in beta-sheet) which is similar in TPI from all three species. Reversible dissociation of the dimeric enzyme in guanidine followed by dialysis, although permitting full recovery of catalytic activity, results in refolded dimers with decreased alpha-helix. These conformational changes induced by ligand binding, pH, or reversible dissociation explain, in part, the differences in the chemical and physical properties of the enzyme from the three species at alkaline pH, the increased lability of the dissociated/reassociated enzyme, and corroborate 31P NMR data on substrate-induced conformational changes. These studies also support the concept of molecular wear and tear whereby ligand binding at the catalytic center induces conformational changes that increase the probability of covalent modification and ultimate degradation of the protein. PMID- 1586171 TI - Patterns of metabolic adaptation for preterm and term infants in the first neonatal week. AB - There have been few comprehensive accounts of the relationships between glucose and other metabolic fuels during the first postnatal week, especially in the context of modern feeding practises. A cross sectional study was performed of 156 term infants and 62 preterm infants to establish the normal ranges and interrelationships of blood glucose and intermediary metabolites in the first postnatal week, and to compare these with those of 52 older children. Blood glucose concentrations varied more for preterm than for term infants (1.5-12.2 mmol/l v 1.5-6.2 mmol/l), and preterm infants had low ketone body concentrations, even at low blood glucose concentrations. Breast feeding of term infants and enteral feeding of preterm infants appeared to enhance ketogenic ability. Term infants had lower prefeed blood glucose concentrations than children but, like children, appeared to be capable of producing ketone bodies. This study demonstrates that neonatal blood glucose concentrations should be considered in the context of availability of other metabolic fuels, and that the preterm infant has a limited ability to mobilise alternative fuels. PMID- 1586172 TI - Pulmonary and systemic arterial pressure in hyaline membrane disease. AB - Systolic pulmonary arterial pressure was determined serially over the first 10 days of life in 33 babies with hyaline membrane disease by measuring the peak velocity of pansystolic tricuspid valve regurgitation, using Doppler ultrasound, and applying the Bernoulli equation. Results are presented in age groups 0-12, 13 36, 37-72, and 73-96 hours respectively. The incidence of tricuspid valve regurgitation was 92, 97, 80, and 64% (falling to 35% by day 10) compared with 53, 50, 31, and 0% in 17 healthy premature infants. In comparing healthy babies with those with hyaline membrane disease, no allowance was made for right atrial pressure. The derived 'right ventricle to right atrial (RV-RA) pressure difference', was expressed as a ratio of systemic arterial (systolic) pressure. Over the first three days, this ratio fell much faster in the healthy babies. Values were 0.78:1, 0.77:1, and 0.72:1 in babies with hyaline membrane disease and 0.87:1, 0.53:1, and 0.44:1 in healthy babies. Ductal patency was prolonged in babies with hyaline membrane disease (75% on day 4 compared with 6% in healthy babies). The incidence of bidirectional ductal flow, indicating balanced pulmonary and systemic arterial pressures, was 79, 53, 30, and 20%, and in healthy babies was 41% at 0-12 hours and zero thereafter. Pulmonary arterial pressure was then calculated by adding a right atrial pressure estimate of 5 mm Hg to the RV-RA difference when the babies were ventilated. Babies of lower gestation had lower values. The pulmonary: systemic arterial pressure ratio showed considerable temporal variability, but fell with age and was raised by high mean airway pressure and pneumothorax (through a reduction in systemic pressure), and less noticeably by carbon dioxide tension. It did not correlate significantly with other indices of disease severity. Hyaline membrane disease is associated with delayed postnatal circulatory adaptation characterized by pulmonary hypertension, systemic hypotension, and prolonged ductal patency. PMID- 1586173 TI - Central venous pressure in the ventilated neonate. AB - As there is no other measurement of right ventricular preload, central venous pressure (CVP) measurement provides unique and important haemodynamic information. CVP is not measured routinely in neonatology and there is a shortage of data in the ventilated neonate. CVP was measured in 62 ventilated neonates. Thirteen had respiratory disorders (28-42 weeks' gestation, birth weight 860-4390 g) and 49 had congenital heart disease (birth weight 1600-4500 g, age 0.5-30 days). Data from other case reports are also presented. In the babies with respiratory distress, a value of zero was associated with clinical evidence of hypovolaemia and negative values, common in the unventilated neonate, did not occur in those who were ventilated. Values over 7 mm Hg were found in babies with evidence of myocardial dysfunction or persistent fetal circulation but were also found with transmitted high intrathoracic pressure, such as with pneumothorax. In the babies with congenital heart disease, values mostly lay between 4 and 8 mm Hg. Values outside this range, particularly above 8 mm Hg, were usually associated with profound metabolic acidosis, suggesting circulatory failure. While the main use of CVP measurement is in trend analysis, this report suggests that single measurements can be of value, though correct interpretation will depend on the context in which they are made. PMID- 1586174 TI - Phosphatidylcholine composition of endotracheal tube aspirates of neonates and subsequent respiratory disease. AB - The phosphatidylcholine (PC) content of the initial endotracheal tube aspirate was measured in 105 infants intubated for resuscitation or for ventilation for respiratory distress syndrome, using high performance liquid chromatography and postcolumn fluorescence derivitization with diphenyl-1,3,5-hexatriene. Sixty eight had measurable PC. Of the infants who developed respiratory distress syndrome, with or without subsequent chronic lung disease, neither the percentage of dipalmitoylphosphatidylcholine (DPPC) nor the ratio of DPPC to palmitoyloleoylphosphatidylcholine (POPC), showed any correlation with gestational age. However, both parameters were significantly lower overall in this group than in the group of infants who did not develop respiratory distress syndrome. Infants with a ratio of DPPC:POPC less than 3.0 developed respiratory distress syndrome irrespective of gestational age, but there was considerable overlap between groups for values greater than this. The infants with respiratory distress syndrome who went on to develop chronic lung disease had the same initial PC profile as those with respiratory distress syndrome who did not develop chronic lung disease, but differed as a group by being lighter and more premature. The development of chronic lung disease was not associated with a particular initial PC composition. Other factors related to increasing prematurity must therefore be involved in rendering infants vulnerable to developing chronic lung disease. PMID- 1586175 TI - Turnover of exogenous artificial surfactant. AB - The turnover of the artificial surfactant Exosurf after its administration to infants with respiratory distress syndrome was studied. High performance liquid chromatography was used to compare the phosphatidylcholine (PC) composition of serial endotracheal tube secretions from three groups of infants. There were 22 infants who received two doses of Exosurf in 24 hours (group 1), 10 infants who received four doses in 36 hours (group 2), and 41 control infants who did not receive Exosurf. Two parameters were studied: (i) dipalmitoylphosphatidylcholine (DPPC), which is present in both Exosurf and endogenous surfactant, expressed as a percentage of total PC (% DPPC) and (ii) the ratio of DPPC to the entirely endogenous palmitoyloleoylphosphatidylcholine (DPPC:POPC ratio). The administration of Exosurf produced changes in endotracheal tube aspirate PC composition that were detectable for over one week. Four doses of Exosurf in 36 hours prolonged the persistence of these changes compared with two doses in 24 hours, but the numbers of infants were small, and should not be over-interpreted. We conclude that after giving two doses of Exosurf, further doses might best be delayed until after two days, and that further clinical evaluation of dosage regimens is required. PMID- 1586176 TI - Plasma hypoxanthine: a marker for hypoxic-ischaemic induced periventricular leucomalacia? AB - Cerebral ischaemia of the immature brain may result in cavitating periventricular leucomalacia (PVL), an important association of cerebral palsy. Hypoxanthine measured by high performance liquid chromatography was used as a marker of peripartum hypoxia and ischaemia in 116 infants at risk of PVL. PVL was detected by ultrasound. The 81 infants who were unaffected had median (range) gestation of 30 weeks (24-32), weight of 1336 g (724-3790), and a plasma hypoxanthine concentration of 7.8 mumol/l (2.4-48.9). The seven infants who had cavitating PVL had a median gestation of 28 weeks (26-30), weight of 1165 g (682-1860), and a hypoxanthine concentration of 31.9 mumol/l (7.1-149). Cavitating PVL was significantly dependent only on hypoxanthine when controlling for the effects of weight and gestation. This suggests that peripartum hypoxia-ischaemia may be one of the aetiological factors in cavitating PVL. Oxidation of hypoxanthine during reperfusion generates free radicals which may contribute to the tissue destruction of PVL. The association of hypoxia-ischaemia with PVL suggests that PVL may be modified by reducing free radical activity. PMID- 1586177 TI - Somatosensory evoked potentials and outcome in perinatal asphyxia. AB - Somatosensory evoked potentials (SEP) can be measured in the term newborn infant and given an index of function in the areas of the brain most likely to be damaged in perinatal asphyxia. We studied the median nerve SEP in 30 asphyxiated term infants over the course of their encephalopathy and until discharge from the neonatal unit. Three types of response were noted: normal waveform, abnormal waveform, or absence of cortical response. Follow up of the survivors was undertaken at a mean age of 12 months by means of a Griffiths' assessment and neurological examination. Nine infants died of their asphyxial illness and one of spinal muscular atrophy. Of the 20 survivors, three have cerebral palsy, four have minor abnormalities, and 13 are neurodevelopmentally normal. There was a close correlation between outcome and SEP. All 13 infants with normal outcome had normal SEP by 4 days of age, whereas those with abnormal or absent responses beyond 4 days had abnormalities at follow up. PMID- 1586178 TI - Blood leucocyte count in the human fetus. AB - Total and differential leucocyte counts were measured in cord blood samples obtained by cordocentesis (n = 316) or at elective caesarean section (n = 11) from normal fetuses of between 18 and 40 weeks' gestation. The total fetal leucocyte count increased exponentially from 2.8 x 10(9)/l at 18 weeks to 11.8 x 10(9)/l at term. The lymphocyte and monocyte counts increased linearly and the number of neutrophils increased exponentially from a mean value of 0.2 x 10(9)/l at 18 weeks to 0.8 x 10(9)/l at 31 weeks and then 8.5 x 10(9)/l at term. Early myeloid cells, eosinophils, and basophils were observed in 24%, 55%, and 15% of the blood films respectively; they contributed less than 2% to the total leucocyte count and there were no significant changes with gestation. The physiological leucopenia observed in fetuses early in the third trimester may partly explain the predisposition of premature neonates to infection. PMID- 1586179 TI - Fetal leucocyte count in rhesus disease. AB - The effect of fetal anaemia on the total and differential leucocyte counts was studied by examining blood samples obtained by cordocentesis from 177 previously untransfused rhesus affected fetuses at 17-36 weeks' gestation. The mean fetal total leucocyte, lymphocyte, and monocyte counts were significantly lower than the corresponding values in normal controls and there were significant associations between the decrease in these cells and the degree of fetal anaemia. Possible mechanisms for leucopenia include (i) stimulation of erythroid progenitor production at the expense of production of myeloid progenitors, (ii) non-specific haemophagocytosis, or (iii) general suppression of haemopoiesis. Further understanding of the underlying mechanism and the implications of leucopenia as well as the previously reported thrombocytopenia and anaemia may provide a basis for improved antenatal and/or postnatal treatment. PMID- 1586180 TI - Plethysmographic validation of near infrared spectroscopic monitoring of cerebral blood volume. AB - The validation of measurement of cerebral blood volume (CBV) and cerebral blood flow (CBF) using near infrared spectroscopy (NIRS) against jugular venous occlusion plethysmography is described. Repeated measurements in six infants were made using both techniques simultaneously. A close relationship between the two measurements of change in CBV was obtained in five infants. There was also a close relationship for measurement of CBF in four infants. This study confirms the possibility of using NIRS to monitor CBV continuously in the premature infant. This parameter may prove to be of greater clinical value than the intermittent measurement of CBF. PMID- 1586181 TI - Postnatal evolution of slow variability in cerebral blood flow velocity. AB - The evolution of low frequency variability in cerebral blood flow velocity (CBFV) was examined in 30 consecutive admissions of very low birthweight babies. Measurement of CBFV was made on the first day of life and at weekly intervals until discharge. Altogether 133 recordings were subjected to visual classification and described as showing presence or absence of variability at a frequency between 1 and 5/minute. Amplitude of variability was expressed as the largest variation in peak systolic velocity as a percentage of the maximum systolic change. Slow variability was usually obvious and was sometimes present for only part of the minute recorded. There was a significant trend for decreased incidence of slow variability in relation to both postconceptional and postnatal ages. Amplitude of slow variability was also damped with increasing age. Slow variability appeared to be unrelated to the type of sedation, severity of illness, or intracranial pathology; it may be a normal phenomenon in which damping occurs as the autonomic nervous system matures. PMID- 1586182 TI - Intravenous aminophylline and cerebral blood flow in preterm infants. AB - The effect of aminophylline on cerebral blood flow (CBF) was studied in 10 preterm infants who were receiving 6.2 mg/kg intravenously over 20 minutes followed by a maintenance infusion. CBF was measured intermittently using near infrared spectroscopy. Heart rate, blood pressure, oxygen saturation, and transcutaneously measured carbon dioxide tension (TcPCO2) were recorded continuously. Aminophylline administration was associated with a fall in CBF from a median of 15.9 ml/100 g/min to 11.2 ml/100 g/min. Median fall in CBF was 4.1 ml/100 g/min (95% confidence interval 1.7 to 6.5). Heart rate rose and TcPCO2 fell in all infants, median fall being 0.66 kPa. The reduction in CBF was greater than would be expected on the basis of the modest fall in TcPCO2. PMID- 1586184 TI - Caffeine or theophylline for neonatal apnoea? AB - Caffeine, in the dose usually recommended (12.5 mg/kg loading dose and 3 mg/kg daily maintenance), and a higher dose regimen (25 mg/kg loading and 6 mg/kg daily maintenance), was compared with theophylline (7.5 mg/kg loading and 3 mg/kg thrice daily maintenance). The study was a randomised controlled trial in the treatment of a group of 44 infants of less than 31 weeks' gestation (mean gestational age 28.3 weeks) who were suffering from frequent apnoeic attacks. All three regimens produced a significant reduction in apnoeic attacks within 24 hours, but only the higher dose caffeine and theophylline groups showed a significant improvement in apnoea within eight hours. The use of caffeine for the treatment of neonatal apnoea is recommended, because a once daily dose is more easily administered, and because it was found that plasma concentrations were more predictable than those of theophylline. If used in very preterm infants, however, its is suggested that a higher dose regimen than that previously recommended be used to achieve a faster response. PMID- 1586183 TI - Upper airway patency during apnoea of prematurity. AB - Twenty four preterm infants (median birth weight 1120 g and gestation 29 weeks) were studied on 83 occasions by measuring upper airway airflow. Airway patency was detected by the transmission of cardiac impulse up the airway and airway closure by its absence. A total of 309 apnoeas of at least five seconds' duration were recorded. One hundred and eighty (58.0%) were central, 109 (35.5%) mixed, and 20 (6.5%) obstructive. Airway closure was noted in 47% of apparently central apnoeas. Airway closure occurred as apnoea lengthened; the airway remained patent in 38% of apnoeas of 5-9 seconds, 17% of those 10-14 seconds, and 11% of those 15 19 seconds' duration. Airway closure occurred in every apnoea of greater than or equal to 20 seconds. As a consequence, closed apnoeas were longer than open apnoeas (mean 9.7 v 6.6 seconds). In 72% of mixed apnoeas, airway closure was recorded during the central element and this usually preceded obstructive breaths. In 20% of mixed apnoeas and 15.5% of the total group the airways closed, having previously been patent. This occurred after a mean of 3.5 seconds (range 1 17). Mixed apnoea produced a significantly greater drop in arterial oxygen saturation than central apnoea, but only because of the greater duration of mixed apnoea. Airway closure occurs in both central and mixed apnoea and appears to be important in the pathophysiology of mixed apnoea. Central and mixed apnoea are part of a continuum of airway closure and not separate entities. PMID- 1586185 TI - Randomised trial of continuous nasogastric, bolus nasogastric, and transpyloric feeding in infants of birth weight under 1400 g. AB - Forty three infants under 1400 g were fed by a bolus nasogastric, continuous nasogastric, or transpyloric route. There were more complications with transpyloric feeding and no identifiable benefits in the growth rate, oral energy input, or chosen biochemical indices of nutrition. Bolus or continuous nasogastric feeds rather than transpyloric are better routine methods in infants of low birth weight. PMID- 1586186 TI - Risk factors for necrotising enterocolitis: the influence of gestational age. AB - Over a 7 year study period, 82 infants were identified who had necrotising enterocolitis (NEC). A case-control study of the 74 preterm infants was performed to determine those factors which contributed to the development of NEC. The 35 infants with NEC and gestation between 30-36 weeks, when compared with control infants matched for gestational age, had significantly lower birthweight centiles, cord pH, and 1 minute Apgar scores. By contrast, there were no significant differences between the 39 infants with NEC and controls in the 25-29 week group, except that fewer babies with NEC had received breast milk. The eight term babies all appeared to have an obvious predisposing event. We thus propose a model in which susceptibility to NEC is dependent on gestational age. In the 25 29 week range all babies are at risk on the basis of extreme prematurity. In the 30-36 week range asphyxiated and growth retarded babies are at increased risk, while at term a major predisposing event appears to be required. PMID- 1586187 TI - Capillary plasma elastase alpha 1-proteinase inhibitor in infected and non infected neonates. AB - Capillary heel prick plasma elastase alpha 1-proteinase inhibitor (E alpha 1-PI) measured by an immunoassay (using commercially available reagents) was examined as an early indicator of neonatal sepsis. Fifty five infants were studied within 24 hours of birth; 60 (including 10 studied on the first day of life) were examined between two and 30 days after birth. Reference ranges for the neonatal period were developed. Raised E alpha 1-PI concentrations (range 440-2600 micrograms/l) were found at the outset of each of the 24 infectious episodes including five with concomitant neutropenia. On the first day of life, obstetric and neonatal complications were also associated with high concentrations (range 190-2400 micrograms/ml). In infants who survived infection, E alpha 1-PI normalised with antibiotic treatment. It is concluded that capillary heel prick plasma is suitable for E alpha 1-PI testing and raised concentrations provide a sensitive but non-specific index of infection in the first 24 hours after birth. Sequential testing may provide early warning of infectious complications and serve as a guide to the cessation of antibiotic treatment. PMID- 1586188 TI - Breathing pattern abnormalities in full term asphyxiated newborn infants. AB - Perinatal asphyxia is a cause of significant morbidity among full term infants, but breathing abnormalities after an asphyxic insult have not been studied. This report details breathing patterns of 16 full term asphyxiated infants, during the first week of life who were studied by transthoracic impedance pneumocardiograms. Pneumocardiograms were abnormal in 69% of infants in the asphyxiated group and 13% of infants in the control group. Significant differences were noted in the incidence of prolonged apnoea, the percentage of periodic breathing, and in apnoea density. These results indicate that there are significant abnormalities in the breathing pattern of full term infants, during their first week, after perinatal asphyxia. Similar abnormalities have been described in infants who had experienced 'near miss' sudden infant death syndrome. PMID- 1586189 TI - Intracardiac thrombus formation with rapidly progressive heart failure in the neonate: treatment with tissue type plasminogen activator. AB - A newborn is described in whom the use of a central venous line was complicated by septicaemia and by intracardiac thrombus formation with tricuspid valve insufficiency and heart failure. Besides antibiotics, treatment consisted of tissue type plasminogen activator (tPA) for three days. This treatment resulted in the disappearance of the thrombus and the tricuspid insufficiency. No adverse effects were noted. Treatment with tPA should be considered in intracardiac thrombus formation with rapidly progressive heart failure in the neonate. PMID- 1586190 TI - Respiratory timing in intubated neonates with respiratory distress syndrome. AB - Respiratory timing was studied in 100 babies ventilated for respiratory distress syndrome (RDS) during a brief period of continuous positive airway pressure. For the 76 spontaneously breathing babies the mean (SD) inspiratory and expiratory times were 0.31 (0.06) and 0.41 (0.12) seconds. Respiratory rate was predominantly modulated by expiratory time. The severity of RDS was the main influence on expiratory time. PMID- 1586191 TI - Intraventricular haemorrhage after aspiration of ventricular reservoirs. AB - A previously unrecognised complication of aspirating ventricular reservoirs is described. Four infants developed fresh bleeding into the cerebrospinal fluid after reservoir taps; ultrasound confirmed intraventricular blood clot in one case. The technique for aspirating the reservoir may have an important bearing on the incidence of this complication. PMID- 1586192 TI - On the horizon: neonatal lung transplantation. PMID- 1586193 TI - Neonatal nurse practitioners--a view from perfidious Albion? PMID- 1586194 TI - Vascular compromise in newborn infants. PMID- 1586195 TI - Scevole de Ste Marthe of France (1536-1623) and The Paedotrophia. PMID- 1586196 TI - Cerebral blood flow velocity changes after rapid administration of surfactant. PMID- 1586197 TI - Non-invasive assessment of pulmonary arterial pressure in healthy neonates. PMID- 1586198 TI - Respiratory support using patient triggered ventilation in the neonatal period. PMID- 1586199 TI - The prophylactic use of ranitidine in babies treated with dexamethasone. PMID- 1586200 TI - Is 28 weeks of gestation equivalent to 1000 g of birth weight? PMID- 1586201 TI - Dermal and inhalation exposure to dimethoate. AB - Dermal and respiratory exposure and plasma acetylcholinesterase (ChE) activity were monitored on six workers spraying tomato crops under plastic houses with dimethoate [O,O-dimethyl S-(N-methylcarbamoylmethyl) phosphorodithoate]. The mean dermal exposure was 914 mg/day and the mean respiratory exposure was 17 mg/day. The maximum dose received by the spraymen was 18.2 mg/day. It was estimated that 84% of the dermal exposure was to the forearms and hands. Of the body areas monitored, the back of the neck received the least rate of exposure. The results also show a reduction in plasma ChE among spraymen. The mean difference was 37.1% less than the preexposure values, which exceeds the limits set by the World Health Organization. PMID- 1586202 TI - Residue pattern and dietary intake of persistent organochlorine compounds in foodstuffs from Vietnam. AB - Concentrations of polychlorobiphenyls (PCBs), hexachlorocyclohexane isomers (HCHs), DDT compounds (DDTs), hexachlorobenzene (HCB), aldrin, dieldrin, heptachlor and heptachlor epoxide were determined in foodstuffs collected from different locations in Vietnam. Elevated levels of PCBs, DDTs, HCHs, and aldrin and dieldrin were found in animal fat, butter, meat, and seafood. Caviar and butter samples imported from the Soviet Union contained considerably higher amounts of PCBs, HCHs and DDTs. The average daily intake of some organochlorines by Vietnamese people were higher than those observed in most of the developed nations. The dietary intake of DDTs was the highest among various chemicals studied. Interestingly, the daily dietary intake of PCBs was comparable to those in developed countries. Fish, shellfish, prawn, and crab were the primary route of DDTs to humans, whereas cereals and vegetables were the predominant sources of PCBs and HCHs. PMID- 1586203 TI - Uptake of environmental contaminants by small mammals in pickleweed habitats at San Francisco Bay, California. AB - Small mammals were live-trapped in pickleweed (Salicornia virginica) habitats near San Francisco Bay, California in order to measure the uptake of several contaminants and to evaluate the potential effects of these contaminants on the endangered salt marsh harvest mouse (Reithrodontomys raviventris). Tissues of house mice (Mus musculus), deer mice (Peromyscus maniculatus), and California voles (Microtus californicus) from nine sites were analyzed for chemical contaminants including mercury, selenium, cadmium, lead, and polychlorinated biphenyls (PCBs). Concentrations of contaminants differed significantly among sites and species. Mean concentrations at sites where uptake was greatest were less than maximum means for the same or similar species recorded elsewhere. Harvest mice (Reithrodontomys spp.) were captured only at sites where concentrations of mercury or PCBs were below specific levels in house mice. Additional studies aimed at the protection of the salt marsh harvest mouse are suggested. These include contaminant feeding studies in the laboratory as well as field monitoring of surrogate species and community structure in salt marsh harvest mouse habitats. PMID- 1586204 TI - An experimental study on the treatment of hydrofluoric acid burns. AB - A 20% solution of hydrofluoric acid (HF) was applied to the skin of rats and a biomedical observation of the tissues and sera was made. Flushing with running water was effective for HF burns. By applying 2.5% calcium gluconate jelly, concentrations of fluoride in the urine and the tissues surrounding the injured region were reduced. Thus, the results proved that irrigation with running water and jelly applications were evaluated as the most effective therapy among various methods tested for HF burns. PMID- 1586205 TI - Tributyltin-induced effects on early life stages of minnows Phoxinus phoxinus. AB - Toxicity and histopathological effects of tributyltin chloride (TBT) were studied in early life stages of minnows Phoxinus phoxinus. Eggs and yolk sac fry (newly hatched larvae) were exposed in a static-renewal procedure to aqueous TBT concentrations ranging from 0.82 to 19.51 micrograms/L for 3 to 10 days at 16 degrees C and 21 degrees C, respectively. Aqueous TBT concentrations were determined by capillary GC-FPD and revealed a concentration decrease during the static phase. TBT exposure led to mortality, behavioral, gross morphological and histopathological effects. In larvae, increased mortality, deformation of body axis, paralysis and opaque eyes occurred at 4.26 micrograms/L TBT and higher both in the embryonic-larval and larval exposure. Histological changes were evident at initial TBT concentrations of 0.82 up to 19.51 micrograms/L, and were more pronounced after embryonic-larval exposure than after larval exposure. Degenerative alterations occurred in skin, skeletal muscle, kidney, corneal epithelium, lens, pigment layer of the retina and choroid, retina, and CNS including spinal cord. Hydropic vacuolation of the cytoplasm and, in more pronounced cases, irreversible nuclear alterations such as pycnosis, karyorrhexis and karyolysis were also evident. Exposure to 0.82 micrograms/L TBT resulted in alterations in skin, muscle and kidney, with greater effects occurring at 21 degrees C than at 16 degrees C. Toxicity was significantly reduced in the presence of sediment. The observed histopathological effects suggest that early life stages of fish may be negatively affected in environments that are considerably polluted by TBT. PMID- 1586206 TI - Ultrastructural alterations produced in cockerels after mercuric chloride toxicity and subsequent interaction with an organophosphate insecticide. AB - Ultrastructural changes of liver and kidneys of cockerels exposed to mercuric chloride and subsequent interaction with methylobromofenvinphos (IPO 63 compound) were studied. Group A birds were treated for 4 weeks with 300 ppm mercuric chloride in drinking water; Group B birds were treated for 4 weeks with mercuric chloride followed by single oral dose of 240 mg/kg of IPO 63; Group C 240 mg/kg IPO 63 only; and Group D, unexposed controls. Hepatocytes of mercury-IPO 63 interaction group B showed large lysosomes containing myelin bodies, swollen mitochondria with cristeolysis, dilated endoplasmic reticulum and numerous vacuoles containing granular material. Mercury-intoxicated birds showed similar but less severe changes, whereas IPO 63-treated birds showed accumulation of glycogen granules, fat droplets, and few lysosomal bodies as well as other changes. Renal corpuscles of kidney from mercury-IPO 63 interaction birds revealed minor ultrastructural changes as vacuolation, swollen mitochondria of podocytes and slight thickening of the glomerular basement membrane. Proximal tubular cells showed extreme damage such as, microvillar loss, dilation of endoplasmic reticulum, accumulation of lysosomal bodies, glycogen granules, myelin figures, swollen mitochondria with granular material, numerous vacuoles containing degenerated membranous organelles and distorted, pyknotic nucleus with marked dilation of nuclear membrane. Mercury intoxicated birds showed similar but less pronounced changes in tubules. These observations suggest that the effect of mercuric chloride toxicity and then interaction with an organophosphorus insecticide causes extreme damage to hepatic and renal cells that appears to be additive. PMID- 1586207 TI - Residues of p,p'-DDE and mercury in lake trout as a function of age. AB - Lake trout (Salvelinus namaycush) of known age from 1 to 12 years were taken from Cayuga Lake in central New York State in 1991 and p,p'-DDE and mercury were determined in their flesh. The concentrations of p,p'-DDE and mercury increased significantly (p less than 0.001) with increasing age of the fish. The concentration of p,p'-DDE also increased significantly (p less than 0.001) with increasing fat content. The concentrations of p,p'-DDE were much lower than those found in Cayuga Lake trout of similar age captured in 1978. PMID- 1586208 TI - In vitro effects of the nephrotoxins ochratoxin A and citrinin upon biochemical function of porcine kidney. AB - Ochratoxin A and citrinin are nephrotoxic mycotoxins found in a variety of foods and feeds. Before studying possible interactions between these two toxins, their individual biochemical effects were examined in vitro by using renal cortical explants derived from male swine of the Hormel-Hanford strain. The following measurements were performed: macromolecule biosynthesis (protein, RNA, and DNA), respiration (14CO2 from [14C]glucose), organic ion (tetraethyl ammonium acetate, i.e., TEA) transport, and membrane perturbation (protein leakage into medium). Levels of the toxins ranged from 0.001 to 1 mM. Ochratoxin A inhibited macromolecule biosynthesis at a lower concentration (0.001 mM) than did citrinin. Protein and DNA synthesis were particularly sensitive to ochratoxin A. Syntheses of protein and DNA were inhibited at ochratoxin A concentrations of 0.01 and 0.001 mM, respectively. RNA synthesis was less sensitive to the mycotoxin; it was inhibited only 60% at 1 mM, the highest concentration of ochratoxin A tested. Citrinin levels of 0.01 mM were required for inhibition of RNA, DNA, and protein synthesis. Inhibition by citrinin was approximately equal for all three classes of macromolecules. Citrinin was more effective than ochratoxin A in the inhibition of respiration and TEA transport; the minimum effective levels of citrinin were 1 and 0.01 mM, respectively. Serious membrane damage as evidenced by increased protein leakage was not caused by either toxin. Stimulation of respiration, perhaps reflective of uncoupling of oxidative phosphorylation, was produced by an ochratoxin A concentration of 1 mM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586209 TI - [Sign of the prominent papilla]. AB - Renal papillae can be seen ultrasonographically in acute dilatation of the urinary tract as echogenic formations within the ecstatic calices. The foregoing, however, must be distinguished from radiotransparent lithiasis, urothelial neoformation or solid infectious detritus. Occasionally, making the differential diagnosis may entail some difficulty. PMID- 1586210 TI - [Unusual presentation form of testicular neoplasms. Report of 5 cases]. AB - Testicular tumors have a typical form of presentation, but there are also unusual forms that must always be considered. We report on 5 cases of testicular tumors that had an uncommon form of presentation: 3 seminomas (1 anaplastic), 1 teratocarcinoma and 1 carcinoma in situ. All testicular changes, particularly in the young male, must be suspected as being a testicular neoplasm and a complete work up must be performed until the exact diagnosis can be made. Currently, evaluation of the testes by ultrasound is a necessary procedure in the diagnosis of this pathological condition. Because it is non-invasive, simple and low-cost, it is the ideal method of evaluation. PMID- 1586211 TI - [Urologic aspects of Hippel-Lindau disease]. AB - We report on a patient with von Hippel-Lindau disease with special reference to the urological features. Several members of the patient's family had also presented this hereditary disease. Careful follow-up of these patients permits early diagnosis of some of the characteristic tumors. Because it has a tendency to be multifocal and bilateral, surgical treatment of renal carcinoma must be as conservative as possible. For this reason, early tumor excision constitutes the ideal treatment. The importance of family screening and genetic counselling is underscored. PMID- 1586212 TI - [Percutaneous U-loop nephrostomy: our experience]. AB - Thirteen U-loop nephrostomy procedures performed percutaneously in 9 patients are described. Thirty-three percent of these patients had a bilateral, one-stage procedure. This procedure can be performed under local anesthesia and, on average, requires 45 minutes. It is simple, yet it provides many other advantages; i.e., enhanced urinary drainage, easy to change and excellent patient tolerance. For all the foregoing reasons, we consider this procedure to be a valid alternative to open surgery. PMID- 1586213 TI - [Primary ureteral adenocarcinoma. Ureteroscopic diagnosis]. AB - A case of primary adenocarcinoma of the ureter that had been diagnosed by ureteroscopy is described, highlighting the form of presentation and treatment. The anatomopathological features as well as the method employed for diagnosis make this an extremely uncommon case. PMID- 1586214 TI - [Treatment of ureteral lithiasis with laser]. AB - We present our experience in the treatment of ureteral lithiasis with pulsed dye lasertripsy (Pulsolith)**. Evaluation of the results achieved in 67 cases of lithiasis that had been treated from January, 1990 to March, 1991 revealed a success rate of 93%. The remaining cases required the use of other complementary energy to achieve stone fragmentation. The approach, the endoscopic technique using the Olympus ureteroscopes (7.2F-9F) and complementary maneuvers are described. The complications were minimal. We consider this to be the procedure of choice for calculi in the pelvic ureter. Furthermore, we discuss the cost/benefit of this therapeutic option within the context of a lithotripsy unit with a high endoscopic dedication and the possibility of using fine caliber ureteroscopes (Olympus) as well as other options for stone fragmentation (shock wave, ultrasound and electrohydraulic energy). PMID- 1586215 TI - [Echo-Doppler duplex combined with intracavernous injection of prostaglandin E1 in the diagnosis of impotence]. AB - Sixty-two patients that had consulted for impotence were evaluated by intracavernal injection of prostaglandin E1 and duplex echo-Doppler. The internal diameter and the mean flow of the cavernosal arteries were determined by echo Doppler in the flaccid state. Thereafter 20 micrograms of PGE 1 was injected intracavernously and the erectile response was evaluated clinically after 5 to 15 minutes. Another Doppler evaluation was performed during tumescence to study the changes of the internal diameter and the mean flow increase of the cavernal arteries. Twenty-nine patients (46.7%) achieved normal erection after intracavernal PGE 1 and the Doppler study was normal in all but 2 patients (3.2%). The remaining 33 patients (53.1%) failed to achieve normal erection following intracavernal injection of PGE 1. The Doppler study, however, was normal in 7 of these patients (11.2%), which indicates venous leak to be the underlying cause of impotence. There were minor complications (19.3%) presented a small hematoma at the site of injection and 12.9% referred moderate pain at the time of injection) and no patient has a sustained erection for more than 3 hours. The hemodynamic mechanisms and the current concepts relative to the neurologic aspects of erection are discussed. We believe duplex echo-Doppler combined with intracavernal PGE 1 to be a very reliable method in the diagnosis of impotence of a vascular origin. It can distinguish those patients that cannot achieve erection following intracavernal PGE 1 with a normal arterial tree whose impotence can be ascribed to venous leak. PMID- 1586216 TI - [Spermatic cord torsion]. AB - Torsion of the spermatic cord constitutes a surgical emergency. Morphologically and functionally, the fate of the compromised testis largely depends on the time elapsed between the acute episode and surgical intervention. Patients who had been treated for testicular torsion by our group from 1976 to 1989 were requested to return for outpatient evaluation. These patient were divided into two groups according to the time elapsed between the diagnosis and surgical intervention. We observed that surgical correction within 12 hours following presentation permitted testicular salvage. Testicular volume was generally preserved and remained normal or slightly diminished. However, when the time elapsed was over 12 hours, testicular atrophy was observed in 46% of the patients. We can conclude, therefore, that detorsion must be performed as soon as possible. Vaginalis testis eversion will generally achieve stable and lasting fixation. PMID- 1586217 TI - [Urethral advance by the Beck-von Hacker technique: indications and results]. AB - Herein we describe a modification of the Beck-von Hacker procedure which we utilize in the treatment of hypospadias and distal urethrocutaneous fistulas. The indications and the results achieved with this technique are presented. PMID- 1586218 TI - [Treatment of stress urinary incontinence in women, by the Raz technique. Results]. AB - The results achieved with the Raz technique in 65 patients with stress urinary incontinence are presented. Of these, 23 (35.4%) had mixed incontinence. Overall, good results were achieved in 83.1%, defined as correction of incontinence and no micturition disorder. The present study emphasizes the importance of correct diagnosis for surgical indication. This technique is indicated for mixed urinary incontinence and coexisting cystocele or after previous failed antiincontinence surgery. PMID- 1586219 TI - [Unique incision vasectomy: review of 1,800 cases]. AB - We reviewed 1,800 vasectomy procedures using the double lateral scrotal incision and single incision of the raphe that had been performed at the Family Planning Center. The number of complications were minimal for both techniques: 6.5% for the patients submitted to the double incision and 5.5% for those submitted to the single incision procedure. The advantages of the single incision procedure are: it is easy to perform, less anesthesia is required, there are less complications, and the operating time is reduced. PMID- 1586220 TI - [Leukoplakia of the upper urinary tract]. AB - Leukoplakia is a morphological term that attempts to define keratinizing desquamative squamous metaplasia of the transitional epithelium. It is uncommon in the upper urinary tract (less than 100 cases have been reported) and has been attributed to infection or mechanical injury to the epithelium and/or genetic factors. We present a case of leukoplakia in a male patient with renal tuberculosis that had been in remission for the past 15 years. Eight years earlier he had intermittently passed keratin laminas (pathognomonic of leukoplakia) during the course of various episodes of nephritic colic. After discarding a reactivation of tuberculosis and malignancy of the metaplastic lesion, we continued conservative treatment with radiologic and cytologic control evaluations. PMID- 1586221 TI - [Pulmonary fibrosis secondary to nitrofurantoin]. AB - We report a case of pulmonary fibrosis from long-term furantoin therapy after radical surgery for a bladder tumor and urinary intestinal diversion. The patient developed pulmonary superinfection and acute respiratory failure. She initially responded to treatment, but relapsed two weeks later. The underlying pathological condition led to the patient's death. PMID- 1586222 TI - [Complicated hydatid cyst mimicking renal tumor. Diagnosis with fine needle aspiration puncture]. AB - We report a complicated case of hydatid cyst mimicking a renal tumor, diagnosed by fine needle aspiration cytology. The cytological features are described and the diagnostic value of fine needle aspiration biopsy is underscored. PMID- 1586223 TI - [Pelvic abscess and acute urine retention caused by appendicitis]. AB - A 15-year-old male patient with a ten day history of fever and GI symptoms that had been diagnosed as having a suprapubic mass was referred to the Urologic Emergency Unit. Patient work up revealed acute urinary retention and appendiceal abscess. PMID- 1586225 TI - Physical effects of shock waves on the kidney. A commentary based on several experiments. AB - An egg can be an excellent experimental model for it provides us with accurate information on the effects of shock waves on biological structures of acoustic impedance identical to that of human cells and interfaces of small width. The authors divided the experiments into two groups. The one in which the shock wave was focused on the whole egg--its shell is almost transparent to shock waves- showed that hyperpressures on thin interfaces have hardly any destructive effect, whereas in the other in which the egg was used without the shell and the shock wave was directed to the yolk, yolk fragments were thrown into the surrounding water, indicating that destructive effects are caused by the cavitation effect. The authors suggest some penetration ranges of shock waves on the kidney which they consider to be the least harmful. PMID- 1586224 TI - [Wunderlich disease. First manifestation of a renal adenocarcinoma]. AB - We present a case of the classical Wunderlich syndrome or circumscribed extracapsular renal hematoma in a 54-year-old male patient who had consulted for an inguinal mass and hemiscrotal ecchymosis. The patient had referred an episode of intense pain in the left renal fossa and the clinical picture of syncope 3-4 days earlier. Surgery disclosed severe perirenal hemorrhage from an undiagnosed renal adenocarcinoma that had ruptured. PMID- 1586226 TI - Ureterocolic fistula: a case report. AB - The authors report a case of ureterocolic fistula secondary to diverticulitis of left colon. The pathological findings of this uncommon case is described. PMID- 1586227 TI - 1991-1992 National Directory of Certified Nephrology Nurses. PMID- 1586228 TI - ANNA Position Statements. PMID- 1586229 TI - An interview with ANA president Lucille A. Joel: nursing's eye toward current and future health care issues. Interview by Marilyn L. Neff. AB - After two terms as president of the American Nurses Association (ANA), Lucille A. Joel, EdD, RN, FAAN, keynote speaker for ANNA's 23rd National Symposium in Chicago, will share her thoughts on nursing's future role in health care. In this interview, conducted by ANNA President Marilyn L. Neff, MBA, RN, CNN, Dr. Joel discussed current and future issues such as unity among nursing, Nursing's Agenda for Health Care Reform, collective bargaining, equity in workplace settings, community nursing organizations, and nursing faculty shortages. PMID- 1586230 TI - Nursing implications in kinetic modeling. AB - Kinetic modeling has direct implications for nephrology nurses delivering prescribed hemodialysis treatment. Studies indicate that patient outcome in morbidity and mortality are closely related to correct delivery of hemodialysis prescription. Correct nursing management of treatment time, dialyzer efficiency, blood flow rate, and problems of recirculation will contribute to successful delivery of intended dialytic therapy. PMID- 1586231 TI - Balancing quality of care and cost-effectiveness through case management. AB - The changing climate within the health care system has necessitated the exploration of innovative strategies to provide quality-based cost-effective care. At a time when cost, quality, and efficiency are key issues, communication and coordination are crucial. Through a deliberate, collaborative approach to goal-directed care, case management facilitates the linking of quality and cost effective care. PMID- 1586232 TI - Description of the illness experience by adolescents with chronic renal disease. AB - The purpose of this study was to describe the illness experience of five adolescents with chronic renal disease. The adolescents described how renal disease had affected themselves and their daily lives. Implications for nurses when interacting with adolescents with renal disease are discussed. PMID- 1586233 TI - Locating information in the nursing literature. PMID- 1586234 TI - Case management of the anemic patient. Epoetin alfa: focus on reimbursement. AB - Epoetin alfa therapy has been proven effective in treating anemia in dialysis patients; it increases the hematocrit (HCT) and improves the quality of life. The reimbursement policy for Epoetin alfa therapy is very important to dialysis patients; nurses need to understand the policy to help patients with reimbursement and to comply with the provisions for patient monitoring and education. PMID- 1586235 TI - Use of intraoperative hemodialysis for treatment of hyperkalemia in an ESRD patient. AB - The patient met all four of the expected outcomes using intraoperative hemodialysis with follow-up care in the intensive care unit for further stabilization of his condition. For the nephrology nurse, intraoperative hemodialysis adds a possible new dimension to the health care of an ESRD patient who requires surgery. Medically, it provides an alternative to the more common practice of preoperative and postoperative management. It provides the nephrology nurse with the opportunity to use theoretical knowledge as well as technical skills in a very fast-paced, high technology setting to confront a medical and surgical challenge. PMID- 1586236 TI - Prostaglandin E1 analogues: misoprostol. PMID- 1586237 TI - Strengthening our profession and association through mentoring. PMID- 1586238 TI - '"The time has come" the walrus said ...'. PMID- 1586239 TI - Increased risk of cancer in patients with systemic lupus erythematosus. AB - To evaluate the risk of cancer in patients with systemic lupus erythematosus (SLE) a series of 205 consecutive patients (182 women and 23 men) were followed up for cancer through the files of the Finnish Cancer Registry. The follow up consisted of a total of 2340 person years. Fifteen cancers were diagnosed against 5.7 expected (relative risk (RR) 2.6, 95% confidence interval (CI) 1.5 to 4.4). Among the women there were four non-Hodgkin's lymphomas against 0.09 expected (RR 44, CI 11.9 to 111) and two soft tissue sarcomas against 0.04 expected (RR 49, CI 6.0 to 177). When evaluated by a case control study previous treatment with cytostatic drugs showed no influence on the occurrence of cancer in this series of patients with SLE. PMID- 1586240 TI - Upregulation of insulin-like growth factor I gene expression in the lesions of osteoarthritic human articular cartilage. AB - Expression of insulin-like growth factor I (IGF-I)mRNA and IGF-I protein was studied in human osteoarthritic and young articular cartilage by in situ hybridisation and immunohistochemistry. In situ hybridisation showed that relatively low amounts of IGF-I mRNA signal were present in anatomically normal regions of osteoarthritic and young cartilage. In fibrillated osteoarthritic cartilage, however, the signal intensity was significantly higher than in non fibrillated cartilage. Particularly high levels of IGF-I mRNA were present in the surface cell clones of more advanced lesions, the amount of signal being about four to five times greater than in anatomically normal cartilage. The amount of message varied with cartilage depth. In young cartilage there was less IGF-I mRNA in the superficial zone than in the middle and deep zones. In fibrillated regions of osteoarthritic joints the amount of message in surface cells was greater than in deeper regions. A specific human IGF-I antibody was used to show the presence intracellularly of IGF-I protein in osteoarthritic and young cartilage. Raised levels of IGF-I message in osteoarthritic chondrocytes may represent an attempt at increased matrix repair, operating by an autocrine/paracrine mechanism. PMID- 1586241 TI - Effects of tiaprofenic acid (Surgam) on cartilage proteoglycans in the rabbit joint immobilisation model. AB - A well established model of arthritis induced in rabbit knee joints by immobilisation in full extension for 30 days was used to evaluate the in vivo effects of 2.5, 5.0, and 10.0 mg/kg body weight of tiaprofenic acid on articular cartilage proteoglycans. The drug was given subcutaneously every 24 hours during the entire immobilisation period. Immobilised animals not treated with drugs and normal animals were used as controls. In the non-drug treated immobilised animals articular cartilage showed evidence of surface damage accompanied by synovial hypertrophy and effusion. Proteoglycan concentrations were reduced in cartilages of these joints and the incorporation of 35SO2-4 into macromolecular proteoglycans was higher than in cartilages of non-immobilised controls. Gel filtration chromatographic studies of both resident and 35S labelled proteoglycans isolated from immobilised joint cartilage showed reduced aggregation and the presence of degraded proteoglycan subunit species. Whereas the administration of 10.0 mg/kg tiaprofenic acid every 24 hours to immobilised animals exacerbated the degradation and loss of proteoglycans from joint cartilages, 5.0 mg/kg tiaprofenic acid provided some protection of these macromolecules, as shown by the concentrations and extractability of proteoglycans from cartilages, which were comparable with those from non immobilised controls. A high incorporation of 35S into proteoglycans was demonstrated, together with reduced catabolism of proteoglycans, indicating preservation of chondrocyte anabolic activity. At a tiaprofenic acid dose of 2.5 mg/kg, however, no beneficial effects on cartilage proteoglycans could be shown. PMID- 1586242 TI - Structured approach to the investigation of anaemia in patients with rheumatoid arthritis. AB - A group of 28 patients with rheumatoid arthritis who were severely anaemic were investigated for iron deficiency. On the basis of bone marrow studies, the patients were divided into two groups, those with and those without signs of stainable iron in the marrow. This grouping did not distinguish between the severity of their rheumatoid arthritis measured by clinical parameters. Measurement of the red cell count and biochemical parameters in the peripheral blood showed a statistical difference in red cell size, haemoglobin content, and iron binding capacity between the two groups. The statistical variation of these parameters, however, did not allow these measurements to predict bone marrow iron deficiency in any subject. Investigation of the upper gastrointestinal tract by endoscopy showed that acute macroscopic lesions were infrequently associated with anaemia. It was concluded that anaemia in association with rheumatoid arthritis may mimic iron deficiency anaemia, and that simple investigations of the peripheral blood do not accurately show the iron status of the reticuloendothelial system in the presence of a chronic inflammatory disease. For the investigation of severe anaemia in rheumatoid arthritis, bone marrow assessment of iron status should be performed as the initial investigation. In addition, iron deficient patients require investigation of the lower and the upper gastrointestinal tract. PMID- 1586243 TI - Influence of the severity of rheumatoid arthritis on sex differences in health assessment questionnaire scores. AB - In a study of 284 consecutive patients with rheumatoid arthritis attending hospital clinics a previous observation that female patients score higher on the Stanford Health Assessment Questionnaire (HAQ) than men was confirmed. A clinical disease severity score and the spread/severity index also showed that women had more severe disease. Although scores in some categories of the HAQ were higher in women, they were not disproportionately so, providing no evidence that domestic categories of the HAQ are biased against women. A multiple regression analysis showed that the spread/severity index score was the best predictor of HAQ scores, with sex making no significant contribution. The severity of the disease adequately explained the higher HAQ scores in female patients with rheumatoid arthritis. PMID- 1586244 TI - Occurrence of (E)-4-hydroxy-2-nonenal in plasma and synovial fluid of patients with rheumatoid arthritis and osteoarthritis. AB - (E)-4-Hydroxy-2-nonenal (HNE), a cytotoxic propagation product of lipid peroxidation, is present in the synovial fluid (0.54 (0.19) mumol/l; mean (SE), n = 9) and plasma (0.34 (0.09) mumol/l, n = 9) of patients with rheumatoid arthritis. This compound was also found in the synovial fluid (0.24 (0.19) mumol/l, n = 9) and plasma (0.09 (0.03) mumol/l, n = 9) of patients with osteoarthritis. The concentration of HNE in the plasma of patients with rheumatoid arthritis was significantly greater than in patients with osteoarthritis. PMID- 1586245 TI - Tests on hypotheses about osteoarthritis and hip joints. AB - Hypotheses suggesting that hip joints which develop osteoarthritis are congruent, have a single area of peak pressure, and have peak pressure which exceeds normal values were tested. Of 100 hip joints examined on necropsy; two showed an early stage of osteoarthritis and the geometry and pressure distribution under load were assessed in these joints. One joint was congruent, in agreement with the hypotheses, but the other was incongruent. In both joints there were several areas of high pressure, the number and location of which depended on the orientation of the joint. The measured values of pressure in the congruent joint exceeded values found previously in normal hip joints. In the incongruent hip joint the peak pressures were within normal limits. PMID- 1586246 TI - Antibodies to protein P in systemic lupus erythematosus. AB - A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis. PMID- 1586248 TI - Measurement of whole unstimulated salivary flow in the diagnosis of Sjogren's syndrome. AB - The criteria for a clinical diagnosis of Sjogren's syndrome remain controversial and vary widely from study to study. With respect to the oral component it is considered necessary to use some form of objective test, but many of those available are not suitable for use in a busy clinical situation. The purpose of this study was to evaluate a simple method for measuring the whole unstimulated salivary flow. Twenty five patients with Sjogren's syndrome, 69 young control subjects, 20 age matched normal older control subjects and 20 patients with rheumatoid arthritis without Sjogren's syndrome had their salivary flows measured. Whole unstimulated salivary flows in the young control subjects were higher than in all other groups. Patients with primary Sjogren's syndrome had lower flows than either the older controls or the rheumatoid patients. Among the patients with Sjogren's syndrome 52% had a flow of 0.1 ml/min or less compared with only 8% of age matched controls. The positive predictive value of this low flow was 81%. It is concluded that whole unstimulated salivary flows of 0.1 ml/min or less are highly specific for xerostomia. When interpreted in the context of all the clinical findings whole unstimulated salivary flows are useful for diagnosing the oral component of Sjogren's syndrome. PMID- 1586247 TI - Antiphospholipid antibodies and HLA associations in primary Sjogren's syndrome. AB - Blood samples from 65 patients with primary Sjogren's syndrome were evaluated for the presence of antiphospholipid antibodies. Increased levels of antiphospholipid antibodies were found in 13 of 65 (20%) of patients. These antiphospholipid antibodies were predominantly of the IgA isotype, in contrast with the IgG isotype antiphospholipid antibodies found in patients with systemic lupus erythematosus (SLE). The presence of IgA antiphospholipid antibodies in the patients with primary Sjogren's syndrome was not significantly associated with arterial or vascular thrombosis, nor peripheral or central nervous system vasculitis. There was no association with laboratory determined features such as lupus anticoagulant or false positive results of the Venereal Disease Research Laboratory (VDRL) test. Oligonucleotide specific DNA amplification and hybridisation with allele specific probes was used to examine the HLA-D antigens occurring in this group of patients with primary Sjogren's syndrome. Of 13 patients with antiphospholipid antibodies, seven had the genotype HLA-DR2/DR3. However, compared with the whole group of 65 patients with Sjogren's syndrome, no increased occurrence of haplotype DR2 or DR3 was noted. These results suggest that gene interaction between DR2 and DR3 may play a part in the production of antiphospholipid antibodies in patients with Sjogren's syndrome. In contrast with patients with SLE, the IgA antiphospholipid antibodies in patients with Sjogren's syndrome are not risk factors for thrombosis or vasculitis. The presence of IgA antiphospholipid antibodies in patients with Sjogren's syndrome probably reflects its production at mucosal sites of inflammation and the absence of vasculopathy may be due to the inability of IgA antibodies to activate complement. PMID- 1586249 TI - Beta 2 microglobulin in tear fluid from patients with primary Sjogren's syndrome. AB - beta 2 Microglobulin concentration in tear fluid was measured in 35 patients with primary Sjogren's syndrome (SS), in 28 normal control subjects matched for age and sex, and in 18 patients with arthralgias or myalgias and sicca complaints, in whom the diagnosis primary SS had been excluded. Increased beta 2 microglobulin concentrations were found in the patients with SS, but no correlation was found with the duration of the disease, age, or tear fluid production. Tear fluid beta 2 microglobulin determinations may be useful as an adjunctive diagnostic test for primary SS. PMID- 1586250 TI - Nervous system disease, immunological features, and HLA phenotype in Sjogren's syndrome. AB - Twenty seven patients with primary or possible Sjogren's syndrome with neurological manifestations were compared immunologically with 21 patients with Sjogren's syndrome with an intact nervous system. Patients with Sjogren's syndrome were divided into seropositive and seronegative subgroups with respect to the occurrence of one or more autoantibodies (antinuclear antibodies, rheumatoid factor, antibodies to SS-B) in their serum samples. This study of 48 patients indicates that the spectrum of nervous system disease in seronegative and seropositive subgroups is almost indistinguishable. No significant differences were found in the occurrence of circulating immune complexes, the levels of serum complement C3 and C4, or serum IgA, IgM, and beta 2 microglobulin with respect to the neurological manifestations. The serum IgG level, however, was significantly higher in the patients with Sjogren's syndrome with intact nervous systems than in those with neurological manifestations. No significant association was found between the HLA phenotype and nervous system disease. The occurrence of HLA-B8 and DR3 antigens was, however, significantly higher in those patients with antibodies to SS-B than in those without. This finding supports the suggestion that HLA-B8/DR3 may modulate autoantibody responses rather than disease expression in Sjogren's syndrome. PMID- 1586251 TI - Influence of decontamination on induction of arthritis in Lewis rats by cell wall fragments of Eubacterium aerofaciens. Arthropathic properties of indigenous anaerobic bacteria. AB - Although the cause (or causes) of rheumatoid arthritis is unknown, many workers have suggested that microorganisms play a part. The intestinal flora in particular has been related to the development of joint inflammation. It has been shown previously that cell wall fragments of several anaerobic Gram positive intestinal bacteria of human origin are arthritogenic after a single intraperitoneal injection in Lewis rats. The part played by indigenous microflora in this model has now been studied by decontaminating Lewis rats before the injection of Eubacterium aerofaciens cell wall fragments. The pattern and severity of arthritis appeared to be comparable in decontaminated and control rats. The second goal of this work was to isolate arthritogenic bacteria from the autochthonous intestinal flora of rats. Only a limited number of bacteria showing a resemblance to arthritogenic strains from human intestinal flora (i.e. E aerofaciens and Bifidobacterium adolescentis) could be isolated. These strains did not induce chronic arthritis after intraperitoneal injection. This may explain why spontaneous arthritis did not develop in Lewis rats. PMID- 1586252 TI - Effect of iron complexes on adjuvant arthritis in rats. AB - When a total dose infusion of iron dextran is given to anaemic rheumatoid patients an exacerbation of inflammatory synovitis in previously affected joints is observed. The adjuvant arthritis model of inflammation in rats has been used to investigate the mechanism of iron promoted synovitis. Either iron dextran (5 mg injected intravenously) with a dextran C control, or iron sorbitol (7.5 mg injected intramuscularly) with a sorbitol citrate complex control was given at the onset of clinical joint inflammation. Iron dextran significantly increased joint inflammation (assessed by joint scoring) at days 12, 13, 14, and 16 after injection. Similarly, iron sorbitol produced a significant increase in the joint score at days 17, 18, 19, and 21. In addition, extensive osteoporosis was observed in the rats treated with iron sorbitol. These pro-inflammatory effects of iron coincide with the presence of positive results for synovial iron (III) using Perl's test and neutrophil infiltration. The results of this study suggest that the iron induced increase in synovitis in adjuvant arthritis is a result of iron promoted oxidative damage and is not likely to be due to the dextran C or the sorbitol citric acid components. It is suggested that a similar mechanism may occur in rheumatoid patients given iron supplements. PMID- 1586253 TI - Predictive value of synovial fluid analysis in juvenile chronic arthritis. AB - To investigate the value of synovial fluid analysis in predicting the articular evolution of juvenile chronic arthritis, synovial fluid from 29 patients with oligoarticular onset juvenile chronic arthritis were examined prospectively. The patients were subsequently classified after a three year period of observation as having polyarticular (10 patients) or pauciarticular (19 patients) disease. The synovial fluid samples were analysed for total and differential white blood cell count, total protein, beta 2 microglobulin, and total complement activity. For comparison, synovial fluid samples from 95 patients with adult onset rheumatoid arthritis were also analysed. In patients with polyarticular disease polymorphonuclear cells and beta 2 microglobulin concentrations were higher than in the patients with pauciarticular disease (80 (29.2) v 58.1 (25.3), and 3.6 (1.2) v 2.2 (0.5) mg/l, respectively), but there was no significant difference from the patients with rheumatoid arthritis. Synovial fluid analysis may be useful in predicting the evolution of juvenile chronic arthritis and improve definition of its subtypes. PMID- 1586254 TI - Epidemiology of rheumatic diseases in rural and urban populations in Indonesia: a World Health Organisation International League Against Rheumatism COPCORD study, stage I, phase 2. AB - To determine the incidence of musculoskeletal pain, disabilities, and help seeking behaviour, a questionnaire was administered to a rural population of 2184 men and 2499 women and an urban population of 481 men and 590 women aged over 15 years by house to house interviews with completion rates of 95.2% (rural) and 97.1% (urban). The incidences of pain in the joints, back, or neck were 23.6% (rural) and 31.3% (urban). The incidence of disability due to an inability to walk, lift, carry, and dress was 2.8% (rural) and 0.9% (urban). The percentage of the population with pain who had to stop work owing to disability was 75% (rural) and 78% (urban). Official health care facilities were used by 62% (rural) and 71% (urban) of the population. Traditional health care was used by 87% (rural) and 89% (urban). The high percentage of subjects unable to work was due to a predominance of manual labour occupations (rural, 90%, urban, 80%). The age and sex specific incidence of rheumatic diseases in these populations were similar to other developing and developed countries. The primary rheumatology service was inadequate due to the low priority given by the health service to non communicable diseases and inadequate rheumatology teaching of the primary health care doctors during undergraduate training. Musculoskeletal pain is a major public health problem in Indonesia and is still not fully appreciated. PMID- 1586255 TI - Adult onset Still's disease: clinical experience with 18 patients over 15 years in northern India. AB - Over a 15 year period 18 patients (eight men, 10 women), 16-50 years old, were diagnosed as having adult onset Still's disease. Fever and arthralgia were always present but prominent lymphadenopathy was uncommon and the serosa were rarely affected. The typical rash of this disease was observed in nine patients. Several complications, including deforming arthritis, amyloidosis, granulomatous hepatitis, uveitis, scleritis, cutaneous vasculitis, and cardiomyopathy, were observed during follow up. Two patients were affected by a nosocomial infection during immunosuppressive treatment for uncontrolled disease. There were no characteristic features at necropsy. Ten patients had a monocyclic course that responded well to aspirin and indomethacin, whereas eight had a polycyclic pattern which invariably required treatment with corticosteroids. Serious complications developed exclusively in the latter group. This group of patients requires early, intensive disease modifying treatment. PMID- 1586256 TI - Intra-articular rheumatoid nodules and triggering of the knee joint. AB - Rheumatoid nodules are a common extra-articular manifestation in rheumatoid arthritis. Intra-articular localisation of these nodules is rare and may produce clinical symptoms. Seven patients with walking problems due to an intra-articular rheumatoid nodule, which became entrapped on the ridge of the tibial plateau of the knee joint resulting in a phenomenon referred to as trigger knee, are described. After excision of the nodules all symptoms completely disappeared. PMID- 1586258 TI - Condensing osteitis of the clavicle: magnetic resonance imaging as an adjunct method for differential diagnosis. AB - Condensing osteitis of the clavicle is a benign disorder leading to osteosclerosis of the medial end of the clavicle. The differential diagnosis between condensing osteitis of the clavicle and ischaemic necrosis of the medial clavicular epiphysis (Friedrich's disease), osteoid osteoma, and low grade osteomyelitis can be difficult. In the case history reported here, magnetic resonance imaging was a useful non-invasive procedure for the diagnosis of condensing osteitis of the clavicle. PMID- 1586257 TI - Bezafibrate induced rhabdomyolysis. AB - The case is presented of a 70 year old woman with mild hypercholesterolaemia and hypertension who was readmitted to hospital six months after a previous admission for angina pectoris. The patient was treated with verapamil, nifedipine, and aspirin, and had been receiving bezafibrate (400 mg every 12 hours) for the previous 40 days. Twenty four hours after admission she developed podagra, which was treated with indomethacin (100 mg daily). Eight days after admission myocardial infarction was suspected, and the next day she presented with symptoms of rhabdomyolysis, which was confirmed by laboratory tests. Bezafibrate was withdrawn and the patient became asymptomatic after seven days. It is recommended that doctors should be aware of the possibility of patients, especially those with impaired renal function, developing rhabdomyolysis while being treated with bezafibrate. PMID- 1586259 TI - Articular manifestations of Scheie's syndrome. AB - A patient with the clinical and biochemical features of Scheie's syndrome is reported. Radiological investigation has shown severe progressive juxta-articular cystic lesions, which have not, to our knowledge, previously been described in Scheie's syndrome. PMID- 1586260 TI - Mixed connective tissue disease associated with autoimmune hepatitis and thyroiditis. AB - The case is reported of a 27 year old woman who had mixed connective tissue disease (MCTD) associated with chronic active hepatitis and thyroiditis. Although hepatomegaly is sometimes observed in MCTD, only four cases of MCTD and chronic active hepatitis have been described. It is thought that this is the first report of an association between MCTD, chronic active hepatitis and thyroiditis. PMID- 1586261 TI - Cerebral occlusive vasculopathy in systemic lupus erythematosus and speculation on the part played by complement. AB - A 35 year old woman with systemic lupus erythematosus and hypocomplementenaemia presented with new onset seizures and subsequently died. At necropsy, widespread microinfarctions of the cerebral cortex were found to be predominantly due to the formation of leucoaggregates within small blood vessels without any vasculitis. PMID- 1586262 TI - Polyarthritis as the presenting symptom of the occurrence and recurrence of a laryngeal carcinoma. AB - A 50 year old male smoker presented with an identical seronegative polyarthritis before both the occurrence and recurrence of a laryngeal tumour. The interval between the joint symptoms and discovery of the tumour was 11 and 13 months respectively. Treatment of the tumour resulted in complete disappearance of the arthritis on both occasions. PMID- 1586263 TI - Palmoplantar pustulotic arthro-osteitis of the peripheral joints with no sternocostoclavicular lesions. AB - A 45 year old woman presented with swelling and pain on joint movement of her knees, although joint movement was relatively well maintained. Five years previously the patient had been diagnosed as having pustulosis palmoplantaris by a dermatologist. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) had no effect, but treatment with 5 mg/day prednisolone caused remission of both the joint pain and swelling and the pustulosis palmoplantaris. There were no sternocostoclavicular lesions at any time during treatment. Clinical findings in this patient were different from previous reports and she was diagnosed as having palmoplantar pustulotic arthro-osteitis affecting the peripheral joints. PMID- 1586264 TI - Siebrandus Sixtius: evidence of rheumatoid arthritis of the robust reaction type in a seventeenth century Dutch priest. AB - Rheumatoid arthritis of the robust reaction type has been diagnosed in a seventeenth century Dutch priest, Siebrandus Sixtius, based on pictorial evidence of typical hand deformities and historical evidence affirming that he had chronic nodular rheumatism for many years. This case report, in conjunction with other pictorial depictions of probable rheumatoid arthritis, questions the view that rheumatoid arthritis is a modern disease which prevailed in the New World and was found in the Old World only after the discovery of America. PMID- 1586266 TI - Normal production of neutrophil activating peptide 1/interleukin 8 in monocytes from subjects with previous yersinia triggered reactive arthritis. PMID- 1586267 TI - Hand radiography: an indicator of upper cervical disease in rheumatoid arthritis. PMID- 1586265 TI - The cytoskeleton and its importance as a mediator of inflammation. PMID- 1586268 TI - Positive antinuclear antibodies in malignancies. PMID- 1586269 TI - Conjunctival ulceration in Behcet's syndrome. PMID- 1586270 TI - Haloperidol blood levels and clinical effects. AB - This study explored the relationships between plasma levels and the clinical effects of haloperidol in 176 acutely exacerbated schizophrenic or schizoaffective patients. After a single-blind placebo period of 1 week (period 1), they entered the double-blind period 2 randomly assigned to one of three plasma levels of haloperidol: low (2 to 13 ng/mL), medium (13.1 to 24 ng/mL), or high (24.1 to 35 ng/mL). Patients whose conditions did not improve in period 2 continued on one of the three haloperidol levels (period 3). Periods 2 and 3 lasted 6 weeks each. Only minor differences in clinical responses were noted among the three levels of haloperidol. These results imply that low or moderate doses of neuroleptics are appropriate for many acutely psychotic patients. PMID- 1586271 TI - A family study of obsessive-compulsive disorder. AB - First-degree relatives of probands with obsessive-compulsive disorder (OCD) (n = 32) and psychiatrically normal controls (n = 33) were blindly interviewed with the use of the Diagnostic Interview Schedule. The morbidity risk for anxiety disorders was increased among the relatives of obsessional subjects compared with that for the relatives of controls, but the risk for OCD was not. Risk for a more broadly defined OCD (including relatives with obsessions and compulsions not meeting criteria for OCD) was increased among the parents of obsessional subjects but not among the parents of controls (16% vs 3%). The findings suggest that an anxiety disorder diathesis is transmitted in families with OCD, but that its expression within these families is variable. The findings also support the current practice of classifying OCD as an anxiety disorder. PMID- 1586272 TI - Subsyndromal symptoms in bipolar disorder. A comparison of standard and low serum levels of lithium. AB - Ninety-four patients with bipolar disorder participating in a random-assignment, double-blind, prospective maintenance trial of standard- (0.8 to 1.0 mmol/L) vs low-range (0.4 to 0.6 mmol/L) serum lithium levels were assessed to determine the presence and significance of subsyndromal symptoms during periods of remission and recovery. A significant relationship was found between prescribed serum lithium level and the probability of major affective relapse and the occurrence of subsyndromal symptoms. Patients given lithium carbonate to achieve low-range levels had 2.6 times the risk of major affective relapse as those given lithium for standard-range levels and nearly twice the risk of developing subsyndromal symptoms. Patients given the low-range therapy showed a greater variance in weekly Psychiatric Status Rating measures, and their symptoms were more likely to worsen at any time than were symptoms in their standard-level group counterparts. The first occurrence of subsyndromal symptoms increased the risk of major affective relapse fourfold. Following the onset of subsyndromal symptoms, the patients originally randomized to receive standard-range lithium therapy were still better protected from relapse than were patients randomized to receive low range lithium treatment. Patients were two times more likely to develop depressive than hypomanic symptoms between acute episodes of illness. However, onset of hypomanic symptoms predicted subsequent major affective relapse twice as strongly as did depressive symptoms. Seventy-six percent of patients who became hypomanic had a major affective relapse, compared with 39% of patients who were subclinically depressed. PMID- 1586273 TI - Polysomnographic characteristics of young manic patients. Comparison with unipolar depressed patients and normal control subjects. AB - Although sleep disturbance is a prominent feature of mania, its polysomnographic (PSG) features have received little study. To investigate more systematically the PSG characteristics of sleep in mania, all-night PSG evaluations were performed for two to four consecutive nights in 19 young manic patients (age range, 18 to 36 years), 19 age-matched patients with major depression, and 19 age-matched normal control subjects. Manic and depressed patients displayed nearly identical profiles of PSG abnormalities compared with normal control subjects, including disturbed sleep continuity, increased percentage of stage 1 sleep, shortened rapid eye movement latency, and increased rapid eye movement density. These results are similar to those reported in previous studies of major depression, and they are consistent with the possibility that the sleep disturbance in mania and major depression is caused by the same mechanism. PMID- 1586274 TI - Adrenal gland enlargement in major depression. A computed tomographic study. AB - To determine whether the well-documented hyperactivity of the hypothalamic pituitary-adrenal axis in depressed patients includes adrenal gland hypertrophy, adrenal gland size was evaluated by computed tomography. Assessments consisted of (1) global ratings by two radiologists ignorant of the diagnostic identity of the subjects and (2) calculation of adrenal volume. Of the 38 patients with major depression, 12 were rated as exhibiting adrenal hypertrophy. Adrenal volumes in the depressed patients were significantly increased when compared with those of normal controls. Adrenal gland size was not correlated with dexamethasone suppression test results, patient age, duration of the depressive episode, or depression severity. These results are concordant with the hypothesis that chronic corticotropin hypersecretion in depression results in adrenocortical hypertrophy. Adrenal gland enlargement may be a measure of cumulative lifetime depression. PMID- 1586275 TI - Relationships over 1 year between lymphocyte subsets and psychosocial variables among adults with infection by human immunodeficiency virus. AB - To examine relationships between immune and psychosocial variables among adults infected with human immunodeficiency virus type 1, 221 subjects without acquired immunodeficiency syndrome were assessed for degree of depression, anxiety, psychiatric symptoms, social support, stressful life events, hardiness, hopelessness, bereavement, and intrusive and avoidant thoughts about acquired immunodeficiency syndrome. At entry, none of 22 psychosocial variables significantly correlated with lymphocyte subsets. Among subjects seen 6 and 12 months later, severity of physical symptoms was associated with greater emotional distress, but the CD4 cell count was predicted by neither clinical ratings of psychopathology and global functioning nor by standardized self-report measures of constructs used in psychoimmune research. We conclude that among our sample, physical symptoms contributed to emotional distress, but emotional distress did not contribute to the CD4 cell count, a marker of disease progression. PMID- 1586276 TI - Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease. AB - Twenty-six patients with moderately severe Alzheimer's disease (AD) and 16 normal control subjects were studied using either quantitative magnetic resonance imaging (MRI) measures of mesial temporal atrophy (15 patients with AD and 16 normal control subjects) and/or quantitative radioactive iodine 123-N-isopropyl iodoamphetamine single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (20 patients with AD and eight normal control subjects). Nine individuals with AD and eight normal control subjects underwent both structural and functional imaging. On MRI, patients and controls were best discriminated using left amygdala and entorhinal cortex volumes, and on SPECT they were best discriminated by relative left temporoparietal cortex blood flow. Combining these MRI and SPECT measures yielded 100% discrimination. Relative left temporoparietal SPECT regional cerebral blood flow and left superior temporal gyral MRI volume correlated best with severity of cognitive deficit in patients with AD. Mesial temporal MRI atrophy exceeded generalized cerebral shrinkage. Both SPECT and MRI regional changes accorded with areas known to be affected by AD neuropathology. PMID- 1586277 TI - Neurobehavioral probes for physiologic neuroimaging studies. AB - The potential of physiologic neuroimaging for contributing to the understanding of behavior and the psychopathologic condition is being enhanced by increased application of "neurobehavioral probes," tasks performed during measurement. Thus far, little attention has been paid to the psychometric properties of such tasks as reliability, difficulty, and construct validity. We propose steps for applying such probes, considering issues in defining the behavior and task selection. Few available neuropsychometric tasks meet criteria for optimal use in neuroimaging studies, and a procedure is outlined for developing new probes. Highlighted are issues encountered during the phases of conceptualization, assembly and screening of items, task construction, and the psychometric validation. A set of language tasks illustrates the process. The procedure may enhance efficiency of acquiring knowledge in this area where the magnitude of potential may be matched by the costs and complexity of research. PMID- 1586278 TI - The LAST award: a not entirely tongue-in-cheek proposal. PMID- 1586279 TI - Phosphomonoesters and phosphodiesters in the brains of schizophrenic patients. PMID- 1586280 TI - Fluid flow through cat dentine in vivo. AB - An outward flow of fluid through exposed dentine was demonstrated in anaesthetized cats. The flow was measured by observing the movement of the fat droplets of dilute milk in a glass capillary (i.d. 30 microns) with a microscope. The capillary was sealed to the dentine with a plastic cap. The resting flow rate through dentine exposed by fracturing off the tip of a cat's canine ranged from 2.8 to 50.9 pl.s-1.mm-2 (mean 18.1, SD 15.9, n = 12). Raising the pressure at the dentine surface to about 15 cmH2O stopped the flow. Immediately after cutting the pulp at the root apex, in 11 of 12 preparations, the flow reversed. The average flow rate was then 3.8 pl.s-1.mm-2 inward (range 8.4 outward to 15.9 inward, SD 5.4, n = 12). The inward flow after pulp section suggests that an osmotic effect may contribute to the net pressure causing flow. The average hydraulic conductance of the exposed dentine was 1.6 x 10(-8) m.s-1.kPa-1 (range 0.5-2.9, SD 0.8) before pulp section. After pulp section, it increased to an average of 2.5 x 10(-8) m.s-1.kPa-1 (range 0.8-5.2, SD 1.3). PMID- 1586281 TI - Effect of timing of administered calcium lactate on the sucrose-induced intraoral demineralization of bovine enamel. AB - A number of soluble calcium salts are known to reduce the demineralization of enamel in the mouth. The present study was undertaken to examine the effects of rinses containing different concentrations of calcium lactate, and the time of giving the rinses with respect to sucrose challenges. Subjects wore palatal appliances containing blocks of bovine enamel whose surfaces were covered with Streptococcus mutans IB 1600, and rinsed with 10% sucrose for 1 min. Changes in iodide penetrability of the enamel, and the pH and extracellular ion concentrations of the streptococcal plaque were determined. When added to the sucrose rinse, 100 or 150 mM calcium lactate reduced demineralization by about 35%, although the plaque pH was not affected. Plaque calcium was elevated but diffused away rapidly so that concentrations after 45 min were close to control values. Plaque inorganic phosphate and lactate were not affected. Ongoing demineralization appeared to be stopped when 100 mM calcium lactate was given 15 min after the sucrose rinse. When the lactate was given 15 min before the sucrose rinse, demineralization was reduced by only about 25%, consistent with the rapid diffusion of plaque calcium. The combination of (i) pretreatment with calcium lactate and (ii) admixture of calcium lactate with sucrose was most effective. Demineralization was reduced about 55% with 100 mM calcium lactate under these conditions, and protective effects were seen with as little as 25 mM. In summary, the findings demonstrate the enamel-protective effect of relatively low concentrations of calcium lactate, and point to the need to sustain a high plaque calcium during periods of maximum acidogenicity. PMID- 1586282 TI - Inhibition of synthesis of rat parotid secretory proteoglycan in a gland slice system. AB - The chondroitin sulphate contained within the secretory granules of the rat parotid gland and its saliva was shown to be in the form of a proteoglycan by using inhibitors of proteoglycan synthesis in a gland slice system. Gland slices were incubated in either p-nitrophenyl-beta-D-xyloside or chlorate in the presence of both [3H]-leucine and [35S]-sulphate. The slices were next homogenized and either the 250 g supernatant fraction (for initial experiments) or secretory granule-containing fractions were isolated. Protein and proteoglycans of these fractions were precipitated in 10% trichloracetic acid (TCA), and glycosaminoglycans in cetylpyridinium chloride. [3H]-leucine and [35S] sulphate were quantitated in each type of precipitate by scintillation counting. The results showed that 1 mM xyloside had no effect on protein or glycosaminoglycan synthesis but blocked incorporation of radiosulphate into TCA precipitable material. Sixteen mM chlorate almost totally inhibited incorporation of radiosulphate into glycosaminoglycan and TCA-precipitable material. These findings demonstrate that the rat parotid secretory chondroitin sulphate is indeed a proteoglycan because its synthesis is blocked by the protein-core analogue acceptor, p-nitrophenyl-beta-D-xyloside. This system offers opportunities for exploring the functional role of chondroitin sulphate proteoglycan in this salivary gland. PMID- 1586283 TI - Electromyographic evidence of local muscle fatigue in a subgroup of patients with myogenous craniomandibular disorders. AB - Ten female patients with myogenous craniomandibular disorders who had complete dentitions and mainly unilateral muscle pain and tenderness to palpation, and 10 healthy female controls, participated in the study. The surface electromyographic signals of masseter and anterior temporal muscles were recorded during 30-s test contractions at 50% of the maximum voluntary clenching effort. A force transducer placed between the central incisors recorded the maximum voluntary bite force. The patients exerted a lower maximum voluntary bite force than the controls (p less than 0.05). In the patients the electromyographic signals of the painful muscles were weaker than those of the painless muscles (p less than 0.01). The signals of the control subjects were stronger than those of the painless muscles of the patients (p less than 0.01). The mean power frequency of the signals, recorded at the start of the 30-s contractions, showed no differences between the painful and painless muscles and between the muscles of the patients and of the controls. The rate of mean power frequency shift in the electromyographic signal, as a response to the 30-s test contraction, was normalized with respect to the amplitude of that signal to account for its amplitude dependency. The painful muscles showed a higher normalized rate of mean power frequency shift than the painless muscles and the muscles of the control subjects (p less than 0.01). These results confirm the presence of an impaired condition in the painful muscles of this group of patients with myogenous craniomandibular disorders. PMID- 1586284 TI - The effect of storage in liquid nitrogen on the isolation of oral yeasts in human saliva. AB - Stimulated whole saliva samples were collected from a group of 127 6-yr-old schoolchildren. Each sample was divided into three parts. The first two, one of which contained added glycerol, were immediately frozen in liquid nitrogen and stored at -196 degrees C for 2 months. The third part was transferred to the laboratory and plated on selective medium for yeasts. Colony counts of the frozen and non-frozen samples were then compared. Statistical analysis showed a highly significant correlation between the counts for frozen and unfrozen samples. A high (40.1%) prevalence of yeast carriers was found, and Candida albicans was the most frequently recovered yeast. PMID- 1586285 TI - Drunken driving and breath alcohol test at the scene of violence in Japan. AB - Road Traffic Law prescribes that no person shall drive any vehicle under the influence of intoxicating liquor. Actually, determination of "influence of alcohol" is based on the standard set by the Cabinet Order that alcohol level exceeds 0.5 mg/ml of blood or 0.25 mg/l of expiration. In 1988, number of traffic accidents by drunken driving is 4,808 cases. Among the accidents by drunken driving the rate of fatal causes is 12%. During about last ten years, both of accidents and fatal cases by drunken driving have been decreasing in number, on the other hand, charged or cited number of violation involved "driving under the influence of alcohol" has been increasing. This fact indicates that the concept of seriousness of driving after heavy drinking has been diffused over Japanese nation, but there is still a tendency among drivers to consider the effect of alcohol on driving operation to be negligible when light drinking. In a sobriety checkpoint, alcohol field test are carried out on breath to screen out impaired driver. The most common device used in Japan is an alcohol detector tube, in which cerite particles coated with chromate are packed. The scale on the detector tube is marked to show a value that is lower by 20% than the actual value concerning its inaccuracy. In our study on accuracy of the alcohol detector tube using samples containing approximately 0.25 mg/l of alcohol, which is legal critical level of alcohol impairment, coefficients of variation were 1.50 to 5.45% and deviations from the analytical results by gas chromatography were 18.2 to 19.5%. PMID- 1586286 TI - Presumption of a history of methamphetamine abuse by postmortem analyses of hair and nails: a case report. AB - By sectional analyses of hair, pubic hair, fingernail and toenail of the descendent who had been a habitual abuser of methamphetamine, the drug was detected in each specimen and the drug concentration in the section containing root was higher than that in the other sections. However, no methamphetamine was detected in the other body fluids and tissues. It was considered that the decedent had used methamphetamine for about 18 months and that the dosage of the drug used for the last 10 days or so was relatively large though he had discontinued injecting the drug for 3-5 days. PMID- 1586287 TI - [Behavioral study on reduction of psychotic and behavioral disorders induced by antitussive and expectorant]. AB - Previously, we reported that psychotic and behavioral disorders induced by repeated abuse of a commercial preparation of antitussive and expectorant (BRON-W Solution, SS Pharmaceut.) was mainly due to caffeine (CAF). In order to reduce such problem, we assessed effects of a preparation containing theophylline (THEO) as the substitution of CAF, and dihydrocodeine (2HCOD), methylephedrine (MEPH) and chlorpheniramine (CPA) on ambulatory activity and discrete lever-press avoidance response in mice. It is well known that THEO is less potent in the central action than CAF, but its relaxant action on smooth muscle is about 2 times as potent as that of CAF. Therefore, the dose of THEO administered was half of that of CAF. A significant increase in the ambulatory activity was produced by the administration of CAF and/or mixed preparations, in which CAF was contained with 2HCOD, MEPH and CPA at the same doses with those in BRON 10 ml/kg. The ambulation-increasing effects of THEO and THEO-containing preparations were less potent than those of CAP and CAF-containing preparations. Furthermore, repeated 5 times administration of CAF-containing 4-drug preparation (CAF + 2HCOD+MEPH+CPA) elicited a progressive enhancement of the ambulation-increasing effect. Whereas, almost the same effect was reproduced throughout the 5 times administration of THEO-containing 4-drug preparation (THEO + 2HCOD+MEPH+CPA). The discrete lever press avoidance response was disrupted (i.e., decrease in the avoidance rate) by CAF-containing preparations. However, THEO-containing preparations did not induce such disruption of the avoidance response, but rather improved the avoidance response (i.e., increase in the avoidance rate).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586288 TI - Behavioral effects of cocoa and its main active compound theobromine: evaluation by ambulatory activity and discrete avoidance in mice. AB - Effects of cocoa and its main CNS active constituent methylxanthine theobromine as well as caffeine were evaluated by ambulatory activity, and discrete lever press and shuttle avoidance in mice. Cocoa (1 g/kg p.o.) and theobromine (10 mg/kg p.o.) significantly increased ambulatory activity. However, the other doses of cocoa and theobromine had no effect on the ambulatory activity. Caffeine increased ambulatory activity with the maximum action at 30 mg/kg p.o. Furthermore, cocoa (0.1, 0.3 and 1 g/kg), theobromine (3, 10, 30 and 100 mg/kg) and caffeine (3, 10, 30 and 100 mg/kg) enhanced the ambulation-increasing effect of methamphetamine (2 mg/kg s.c.). The ambulation-increasing effect of cocaine (20 mg/kg s.c.) was also enhanced by cocoa (1 g/kg), theobromine (10, 30 and 100 mg/kg) and caffeine (10, 30 and 100 mg/kg). On the other hand, comparatively higher doses of theobromine and caffeine disrupted the well established avoidance response. Thus, the avoidance rate was significantly decreased by theobromine (100 mg/kg and more) and caffeine (30 mg/kg and more) under the lever-press situation, and by theobromine (100 mg/kg and more) and caffeine (100 mg/kg) under the shuttle situation. These dose effect relationships revealed that cocoa contains about 1% theobromine. The present results indicate that we may receive the CNS action of theobromine through consumption of theobromine-containing foodstuffs or beverages in our every day life. PMID- 1586289 TI - [Ultrastructural changes of liver, heart, lung and kidney of mice in a large dose of ethanol injection]. AB - Ethanol was injected intraperitoneally to dd-strain mice (20-25 g) with a dose of 5 g/kg body weight. The animals were sacrificed by the cervical dislocation at 4, 8, 12 and 24 hr after the ethanol injection. The changes of the ultrastructure of liver, heart, lung and kidney were examined by a transmission electron microscope. The results; from 4 hr to 24 hr after ethanol injection, deposition of fat droplets, swelling of mitochondria, enlargement of rough endoplasmic reticulum and loss of glycogen granules were observed in hepatocytes. Also, the edema of hepatocytes and intravascular hemostasis were found. These changes were aggravated with time course. In the heart, intravascular hemostasis, edema of myocardium, remarkable decrease of glycogen, swelling of mitochondria and appearance of I bands of myocardial fibers were observed. The damage to the myocardium by ethanol injection was similar to that associated with ischemia and anoxia. In the lung and the kidney, at early time after ethanol injection intravascular hemostasis and cell edema were observed but no other electron microscopical changes were found during the experiment. At 4 hr and 24hr after ethanol injection the edema of sinusoidal endothelial cell of liver and at 24hr that of endothelial cell of capillaries of heart were observed. These histological results suggest that the cell damages and intravascular hemostasis would be caused mainly by a direct action of ethanol. The damages of the liver and the heart, however, on the time blood ethanol was not detected would be caused by the disturbance of metabolism owing to ethanol oxidation. PMID- 1586290 TI - [Effect of ethanol on the development and maturation of synapses in the rat hippocampus]. AB - Rats of both sexes were exposed to ethanol during the entire period of the fetal life as well as the whole period of postnatal ages, and their brains were investigated at 2, 7, 14, 21, and 70 days postnatally. Control animals were examined at each age. Densities of synapses in the strata radiatum and lacunosum moleculare of CA1 in the hippocampus were analyzed by quantitative ultrastructural techniques. Densities of all synapses in the strata radiatum and lacunosum-moleculare in ethanol-treated group were significantly lower than those of control group on 2, 14, 21 and 70 days. However, there were no significant differences in the ratio of axo-spinous to axo-shaftic synapses between control and ethanol-treated group. In addition, in regard to the rate of reduction in densities of all synapses, no change was detectable between both strata that receive different groups of afferent fibers. These data suggest that chronic administration of ethanol during the fetal and postnatal ages reduces the synaptic density in this area, and that this effect is neither specific to types of synapses nor to sorts of afferent fibers. PMID- 1586291 TI - Clinical indicators and their role in quality management. AB - In this paper the authors look at the proactive role performance indicators can and should play in managing for quality in health care facilities. In particular, they highlight the use of clinical indicators as a means of providing evidence of value-for-money and best quality delivery of care. The argument is presented that management can no longer ignore indicators as a quality assurance tool and an important component of managing for quality over time. The authors demonstrate where indicators fit into the traditional quality assurance cycle and describe strategies for analysing problems and setting priorities. They also argue that managers need to invest in management information systems in order to provide the data needed for performance monitoring. Accurate and complete indicator data are needed if the goals of quality management and optimal quality of care are to be achieved. PMID- 1586292 TI - ACHS surveyor recommendations: recent trends in the accident and emergency service. AB - An analysis was made of 82 public hospitals surveyed by the ACHS in 1990 that had received recommendations for improvement within their Accident and Emergency service. The major areas requiring attention included quality assurance, scope of service, policy and procedure manuals, signposting and the appointment of a medical practitioner responsible for the service. The analysis also revealed that 90% of the recommendations for improvement made by ACHS surveyors at a previous survey had been fully or partially implemented upon resurvey in 1990. PMID- 1586293 TI - Marketing and quality assurance: the two faces of Janus. AB - The relationship between quality assurance and marketing has been explored in workshops for physiotherapists. Quality assurance and marketing represent two sides of the same coin in health care. Quality assurance offers formal strategies with which to review performance, while marketing tools enable health professionals to assess the needs of the community within which they operate. Inherent in the concept of the interrelationship of marketing and quality assurance is that quality health care must reflect the changing demands of the consumers. Quality assurance and marketing techniques, performed interdependently, enable health professionals to provide quality, appropriate health care. PMID- 1586294 TI - Quality assurance activity in general practitioner hospital patients: prescription of non-steroidal anti-inflammatory drugs. AB - Prescription of non-steroidal anti-inflammatory drugs was recorded for 6 weeks in general practitioner hospital inpatients as a quality assurance activity. Concomitant use of H2 receptor antagonists and diuretics was also recorded. The survey was repeated 1 year later when it was found that the use of non-steroidal anti-inflammatory drugs had fallen from 30% of all patients to 24% in the follow up study. PMID- 1586295 TI - A comparison of quality of care using Phaneuf's Nursing Audit. AB - The quality of nursing care delivered to two groups of patients suffering from diabetes mellitus was examined. Using Phaneuf's Nursing Audit, a retrospective audit of the nursing documentation regarding the care of all patients was carried out, and a comparison made of the numeric scores obtained. The nursing care of the group of patients from the Professional Nursing Unit (PNU) obtained mean scores which were 26.4% higher than those obtained by the group from the general hospital wards. There are major variations in scores in specific areas. These give rise to some questions regarding the value to nurses of the caring and nurturing component of nursing work, and how this is affected by differing philosophies and environments. PMID- 1586296 TI - Organizing for quality in a base hospital. AB - This paper examines the current situation regarding the implementation of quality assurance (QA) programmes in relation to the Tamworth Base Hospital and Health Service. The importance of organizational design and the establishment of a Quality Resource Department are examined as means of achieving effective QA. PMID- 1586297 TI - Breast cancer in the elderly: treatment of operable disease. AB - Between 1976 and 1985 122 elderly patients aged 70 years and over, were treated for 'operable' invasive breast cancer (UICC stage I-IIB). A tendency towards less aggressive investigation and treatment was noted in the elderly. Of 117 patients undergoing surgery, 79 (68%) had 'full' conventional treatment, either mastectomy with axillary clearance, sampling or radiotherapy, or local excision with radiotherapy. In 38 patients (32%) management of the breast or axilla was considered to have been less complete than the usual practice for younger patients ('limited' treatment group), either local excision without radiotherapy or simple mastectomy alone. The 'limited' treatment group were significantly older than the 'full' treatment group but were comparable for tumour size, clinical nodal status and oestrogen and progesterone receptor levels. Although there was no survival difference between the groups, those in the 'limited' treatment group were more likely to develop locoregional recurrence (chi 1(2) = 9.2, P = 0.002, log rank test). In practice, management of the elderly often appears to be influenced by chronological age rather than clinical or biological factors. It is suggested that elderly patients sufficiently fit to undergo surgery should be treated along the lines applicable to younger patients. PMID- 1586298 TI - Regression of liver metastases following treatment with yttrium-90 microspheres. AB - Selective internal radiation (SIR) therapy is a technique developed by our group for concentration of Yttrium-90 microspheres into liver metastases. The technique involves laparotomy, insertion of the catheter into the hepatic artery, redistribution of liver blood flow with vaso-active agents and incremental embolization of Yttrium-90 containing microspheres (SIR spheres) into the liver. Twenty-nine patients with non-resectable liver metastases from primary adenocarcinoma of the large bowel were treated by this technique and followed for a minimum of three months to assess evidence of tumour regression. Response to treatment was measured by serial estimations of carcino-embryonic antigen (CEA) and tumour volumes measured from serial computerized tomography (CT) scanning of the liver. There was a fall in the serum CEA level in all 26 patients in whom the serial estimations of CEA were performed following SIR therapy. The overall mean fall in CEA was 70% of pre-treatment levels with 88% of patients (23 of 26) experiencing more than a 50% fall in pre-treatment CEA levels. In 18 of 22 evaluable patients CT measured tumour volumes decreased following SIR therapy. In 48% of patients (10 of 22 patients) the decrease in tumour volume was more than 50%. SIR therapy results in a high rate of tumour regression in patients with liver metastases secondary to large bowel cancer. PMID- 1586299 TI - Pancreaticojejunostomy for chronic pancreatitis. AB - The treatment of chronic pancreatitis commonly yields disappointing results. Patients with chronic pancreatitis and a dilated pancreatic duct can be treated by longitudinal pancreaticojejunostomy. In order to evaluate the procedure, 20 patients undergoing pancreaticojejunostomy were followed for a median time of more than 5 years. Their clinical characteristics and outcomes have been compared with a group of 43 patients with chronic pancreatitis and small pancreatic ducts. There were no differences between the two groups in the major epidemiological parameters, except that calcification in the gland was more frequently noted in those with large ducts. The operation of longitudinal pancreaticojejunostomy could be accomplished with an acceptable morbidity. There was one death in the postoperative period. Seventy-six per cent of patients were found to have benefited clinically at five years, compared with 48% of those with small duct disease. This difference was statistically significant. Patients who benefited were defined by four factors; they were carrying out their usual occupation at the time of surgery, they were not narcotic dependent at the time of surgery, they had a pancreatic duct width greater than 7 mm and, they had totally abstained from alcohol from before the operation to the time of follow-up. Longitudinal pancreaticojejunostomy probably remains the best surgical treatment for suitable patients with chronic pancreatitis. The operation should only be performed when the pancreatic duct is greater than 7 mm in width. In such patients the operation produces considerable improvement of pain with minimal metabolic disturbance. PMID- 1586300 TI - Inguinal surgery in athletes with chronic groin pain: the 'sportsman's' hernia. AB - Fifty athletes with chronic undiagnosed groin pain underwent surgical exploration and inguinal hernia repair. Six months later, all athletes were sent questionnaires to assess their return to sport, level of pain (using analogue pain scores) and the overall result of their surgery. Operative findings revealed a significant bulge in the posterior inguinal wall in 40 athletes. Forty-four athletes (88%) replied to the questionnaire. Forty-one athletes (93% of respondents) had returned to normal activities. Pain scores indicated a marked improvement in their level of pain (P less than 0.001). Thirty-three athletes (75%) rated the result as good and 10 (23%) as improved. It is concluded that athletes with chronic groin pain who are unable to compete in active sport should be considered for routine inguinal hernia repair if no other pathology is evident after clinical examination and investigation. PMID- 1586301 TI - Collis-Nissen gastroplasty fundoplication for complicated gastro-oesophageal reflux disease. AB - Collis-Nissen gastroplasty fundoplication is a widely accepted operation for patients with gastro-oesophageal reflux disease complicated by oesophageal shortening. Assessment of this operation by 24 h oesophageal pH monitoring has not previously been reported. Our aim was to correlate clinical and endoscopic results with 24 h pH studies. Twenty-nine patients had a gastroplasty fundoplication, as a result of which twenty-five (86%) had an excellent clinical result, 2 (7%) had a good result and 2 (7%) had a poor result. The two poor results were in patients who had previously undergone anti-reflux surgery. All 29 patients had pre-operative pH monitoring. Twenty-three patients had postoperative pH studies. Oesophageal acidification times were normal postoperatively in 16 of 23 patients however, 7 still had an abnormal study. One of the two patients with a poor clinical result was studied and persistent severe oesophageal acidification was demonstrated. The remaining 6 patients with abnormal studies were asymptomatic. Five of the 6 asymptomatic patients also had a normal oesophagogastroscopy with no macroscopic oesophagitis. We conclude that 24 h pH monitoring after the Collis-Nissen operation should only be performed to assess clinically and endoscopically poor results. PMID- 1586302 TI - Spontaneous renal allograft rupture: a disappearing phenomenon in the cyclosporine era? AB - Spontaneous renal allograft rupture occurred in six patients in a series of 384 consecutive renal transplants performed between July 1983 and December 1990. All cases occurred in patients treated with Azathioprine and Prednisolone, and none occurred in patients immunosuppressed with Cyclosporine. Acute allograft rejection was the underlying cause of rupture. All patients underwent urgent operation and repair of the ruptured transplant. Four patients had good renal function 74-84 months after repair, while two returned to dialysis 3 and 65 months after repair because of irreversible rejection. PMID- 1586303 TI - Antibody responses following splenectomy: implications for the timing of prophylactic vaccination. AB - Antibody responses are reduced both in the short- and long-term after splenectomy. It is not known if this reduction is more profound in the immediate postoperative period compared to later, and consequently, whether there would be an advantage in delaying prophylactic vaccination to ensure a greater antibody response. To investigate this, the effect of splenectomy on the primary and secondary antibody response to sheep red blood cells (SRBC) injected into the peritoneum (IP) of adult male Porton rats was measured after either splenectomy (Spx), sham splenectomy (Sham), anaesthesia only (Ans) or no procedure at all (Con). There was no difference in the titres of antibody between the Con and the Ans rats. There was no difference in the titres of antibody between the Sham and Spx rats, but both had significantly lower titres than the Con rats. In a separate experiment, rats were immunized 1 month or 1 year after splenectomy or sham-splenectomy. One month after the operation the antibody response of the Sham rats had increased and did not differ from that of Con rats, but in rats which had been splenectomized there was a long-term suppression of the antibody response, which did not improve for at least one year. The results suggest that, in patients requiring splenectomy for trauma and not able to be vaccinated before operation, there may be no advantage in delaying prophylactic vaccination postoperatively. PMID- 1586304 TI - Omentoplasty in abdominoperineal resection of the rectum. AB - An omental pedicle graft, based on the right gastro-epiploic artery to facilitate perineal healing, was used in 20 cases of abdominoperineal resection of the rectum. There was one postoperative death. Primary healing of the perineum occurred in all cases. The technique is described and recommended. PMID- 1586305 TI - Percutaneous dilatational tracheostomy complicated by delayed life-threatening haemorrhage. AB - Percutaneous dilatational tracheostomy has become increasingly popular as an alternative to formal surgical tracheostomy. We report a case of profuse, life threatening haemorrhage which occurred after percutaneous dilatational tracheostomy. PMID- 1586306 TI - Neurogenic claudication secondary to vascular disease. AB - Neurogenic claudication is characterized by sensory symptoms which appear during exercise or while maintaining a fixed posture. They are paraesthetic in quality, may be associated with 'march' phenomena, and patients may have bowel and bladder disturbance. The problem is most commonly secondary to lumbar canal stenosis (LCS) but rarely due to aortic disease, as shown in this case report. This report concerns a 66 year old woman who presented with symptoms of paraesthesia radiating from the buttocks to the thigh and, intermittent loss of bladder and bowel function, all associated with walking. There were no associated symptoms of vascular claudication. Clinically, there was evidence of aorto-iliac obstruction with absence of femoral pulses and a vascular index of 0.4 at both ankles. Neurological examination was normal at rest but the left ankle jerk was absent immediately after exercise. Myelogram and computerized tomographic (CT) scan were normal. An aortogram revealed a very tight irregular stenosis of the aorta at the level of the renal and mesenteric arteries. Very few lumbar vessels were seen. An aortic endarterectomy via a thoraco-abdominal approach was performed and an aortobifemoral graft inserted. The patient's symptoms resolved following this procedure. We postulate that her symptoms were caused by a 'steal' from the blood supply to the cauda equinda due to the severe athromatous disease of her upper abdominal aorta. PMID- 1586307 TI - Primary adenocarcinoma in a colonic 'oesophageal' segment. AB - A case of primary adenocarcinoma of the colon in a segment used to reconstruct after an oesophageal resection is reported. The original lesion was a relatively advanced adenocarcinoma of the gastro-oesophageal junction. An ACPS 'C' colon carcinoma was diagnosed 12 years later. A curative resection was achieved. The literature is reviewed in regard to late complications in colonic interpositions, including primary carcinomas. PMID- 1586308 TI - Ovarian actinomycosis presenting as acute peritonitis. AB - A patient with acute peritonitis due to ovarian actinomycosis and the association of this disease with the intrauterine contraceptive device is discussed. Because adequate treatment requires prolonged antibiotics the diagnosis should be sure. Unfortunately if antibiotics are given pre-operatively culture is usually unsuccessful and thus careful examination of all removed material is essential. As many of these women are of child bearing age surgical intervention should aim to preserve fertility wherever possible. PMID- 1586309 TI - Vertical subluxation of the patella: an unusual feature of multiple epiphyseal dysplasia. AB - Abnormally shaped, usually double-layered, patellae are recognized as occurring in multiple epiphyseal dysplasia. The case described is unusual in that an associated defect appeared in the femur and resulted in mechanical symptoms. PMID- 1586310 TI - Total thyroidectomy: indications, technique and training. PMID- 1586311 TI - Total thyroidectomy. PMID- 1586312 TI - Total thyroidectomy: its role in the management of thyroid disease. AB - Of 7812 patients treated for thyroid disease in the Endocrine Surgical Unit at the Royal North Shore Hospital, 825 underwent total thyroidectomy as an initial procedure. One third of these patients (269) were operated on for malignancy and the remaining 556 were treated for benign conditions such as multinodular goitre (405), Graves' Disease (79) and thyroiditis (45). The rate of recurrent laryngeal nerve palsy was 0.5% while permanent hypoparathyroidism occurred in 0.6% of cases, the low complication rate being due to the technique of capsular dissection employed in the Unit. The number of total thyroidectomies performed as a percentage of all thyroid operations has risen from 4% in 1970 to more than 40% in 1990. The majority of this increase has been due to surgery for multinodular goitre where the proportion of patients treated by total thyroidectomy now exceeds 80%. A similar but smaller increase has been seen in an analysis of the New South Wales figures for all other public and private hospitals. It is concluded that the complication rate from total thyroidectomy can no longer be used to argue against its use as the definitive operation for malignant disease of the thyroid. Furthermore, in view of the risks of re-operative surgery, total thyroidectomy should be considered the operation of choice for most benign disease affecting the whole thyroid gland such as multinodular goitre, thyroiditis, and in a significant number of goitres affected by thyrotoxicosis. PMID- 1586313 TI - Total thyroidectomy: the technique of capsular dissection. AB - This paper describes the technique of total thyroidectomy using capsular dissection. Total thyroidectomy is a safe straightforward anatomical procedure in which meticulous dissection can provide protection to the parathyroid glands and to the recurrent laryngeal nerve. This protection is achieved by using capsular dissection, hugging the gland and dividing the tertiary branches (i.e. the third order of division) of the vessels while dissecting the parathyroid glands with their vascular pedicles free from the thyroid surface, with minimal exposure of the recurrent laryngeal nerve and disturbance of its blood supply. Total thyroidectomy removes all visible thyroid tissue although it is permissible to leave a very small remnant of tissue (less than a fraction of a gram) in the region of the ligament of Berry in order to protect the recurrent laryngeal nerve and the blood supply to the parathyroid glands. This technique ensures that the incidence of complications, including permanent hypoparathyroidism and recurrent laryngeal nerve palsy, is reduced to a minimum. PMID- 1586314 TI - Veterinary education: challenges of the future. PMID- 1586315 TI - Progressive ethmoidal haematoma in horses. AB - Progressive ethmoidal haematoma was diagnosed in 12 Thoroughbreds, 1 part- Arab and 1 stock horse. Ages ranged from 3 to 18 years and both males and females were affected. Diagnosis was based on history, clinical signs, endoscopic and radiographic findings, and was confirmed histologically in 10 cases. Eleven (78%) of the lesions were unilateral and 3 (22%) were bilateral. Two horses were euthanased on diagnosis, 4 were treated conservatively. Of the latter, 3 were euthanased 6 to 24 months after diagnosis, due to progression of the lesions, while 1 case resolved completely within 13 months. Eight horses were treated by surgical excision of the lesion. Three died in the post-operative period, 3 were euthanased within 48 months after recurrence of the condition, and 2 had no recurrence within 60 and 72 months, respectively. PMID- 1586316 TI - The distribution and prevalence of Theileria buffeli in cattle in Queensland. AB - The distribution and prevalence of Thelleria buffeli in Queensland cattle were investigated using serum samples and blood films collected primarily for brucellosis surveillance and tick fever diagnosis. Serums from 8654 cattle from 357 farms throughout Queensland were examined by an indirect fluorescent antibody test for antibody to T buffeli. In addition, 347 peripheral blood films collected from 147 farms in south-eastern Queensland were examined for piroplasms of T buffeli. The overall herd and animal prevalences for T buffeli were 75% and 41%, respectively. There was significant variation among regions in both herd and animal prevalences (P less than 0.001). Herd and animal prevalences were highest in the north and east decreasing westward. The results indicate that T buffeli is more widespread in Queensland than previously thought. PMID- 1586317 TI - Reconstruction of the parotid duct in a horse using an interposition polytetrafluoroethylene tube graft. AB - A Thoroughbred gelding was referred for treatment of a parotid duct fistula. This had developed after the referring veterinarian had excised a portion of the duct, and ligated the proximal end, as a means of treating a recurring sialocoele. This report describes the successful surgical reconstruction of the excised 15 cm portion of the parotid duct using an interposition polytetrafluoroethylene tube graft. PMID- 1586318 TI - Controlled-release anthelmintic treatment of milking goats. PMID- 1586319 TI - Fungal arthritis due to infection by Candida famata in a horse. PMID- 1586320 TI - Use of a controlled-release albendazole capsule in goats. PMID- 1586321 TI - Acquired pyloric stenosis and gastric retention in a mare. PMID- 1586322 TI - An unusual trematode infecting domestic chickens. PMID- 1586323 TI - Lack of anthelmintic effect of Calliandra calothyrsus in sheep. PMID- 1586324 TI - The association of maternal and socioeconomic characteristics in metropolitan Adelaide with medical, obstetric and labour complications and pregnancy outcomes. AB - Multiple regression analysis was used to measure associations of maternal age, race, gravidity, marital status and socioeconomic status with medical problems and pregnancy outcomes. The study population comprised all singleton births to residents of metropolitan Adelaide (in South Australia) during 1988 that were included in the State's perinatal statistics collection. The results indicate that in metropolitan Adelaide, low socioeconomic status is related to a higher risk profile of mothers and babies. It also highlights that there is a strong association of divorce and separation with medical problems and an adverse pregnancy outcome. Poorer outcomes are also seen in never married women, teenage women, older women, non-Caucasian women and primigravid women. These poorer outcomes in older women and primigravidas include higher risks of low birth weight and prematurity of their babies. The study also demonstrates that groups that are less likely to have choice of obstetric care, eg. teenage women, non Caucasian women, and women of low socioeconomic status, have a lower odds of obstetric intervention as characterized by nonspontaneous labour and elective Caesarean section. PMID- 1586325 TI - Antenatal loss of one of twins. AB - The antepartum loss of a twin with survival of the second twin to delivery was studied in the Tasmanian population from 1980 to 1989 inclusive. No previous study of an Australian population has been reported. This rare complication occurs in 3.5% of twin pregnancies. The outcome of these pregnancies and the outcome for the surviving twin are discussed. PMID- 1586326 TI - The effects of chronic maternal hypotension during pregnancy. AB - The relationship between chronic maternal hypotension and obstetric outcome was examined retrospectively in a group of 134 pregnant women and compared with a normotensive control group. The hypotensive women had significantly increased risks of delivery before the 38th week of gestation, lower birth-weight of babies for gestational age, and postpartum complications. In addition, the rates of preterm delivery before 37 weeks' gestation, birth-weight less than 2,500 g and significant meconium-staining of the amniotic fluid were higher in the hypotensive group, although these results did not reach statistical significance. These data support the need for a prospective study of the effects of chronic hypotension during pregnancy. PMID- 1586327 TI - Racial variation in serum uric acid concentration in pregnancy: a comparison between European, New Zealand Maori and Polynesian women. AB - A prospective study was undertaken to measure serum uric acid levels in normal pregnant women of different races, to ascertain if there was any significant interracial variation. A total of 48 women were studied of which 13 were European, 11 New Zealand Maori, 22 Pacific Islanders and 2 Indian. In the second trimester, European, Maori and Cook Island women had similar uric acid levels and other Polynesian groups showed significantly higher levels. In the third trimester, both Maori and Cook Island women showed a marked rise so that their levels came to equal those of other Polynesian groups, all 3 having significantly higher levels than European women. The importance of these observations relates to the use of uric acid levels in the management of patients with gestational proteinuric hypertension. It is possible that in these cases unusually high results may alarm the clinician into hasty intervention. PMID- 1586328 TI - Premature rupture of the membranes. PMID- 1586329 TI - A comparison of Syntocinon infusion with prostaglandin vaginal pessaries when spontaneous rupture of the membranes occurs without labour after 34 weeks gestation. AB - In a prospective randomized trial of 106 patients who had spontaneously ruptured their membranes greater than or equal to 4 hours in the absence of labour, vaginal prostaglandin E2 pessaries and intravenous Syntocinon were compared. There was no significant difference in the treatment to delivery times between the 2 groups. The number of operative deliveries in each group were comparable. No untoward side-effects were noted. The use of vaginal prostaglandin E2 tablets appears to be a safe alternative to Syntocinon for induction of labour when spontaneous rupture of membranes has occurred in the absence of uterine contractions. PMID- 1586330 TI - Prelabour rupture of the membranes at term and unfavourable cervix; a randomized placebo-controlled trial on early intervention with intravaginal prostaglandin E2 gel. AB - Fifty nine women with prelabour rupture of membranes, unfavourable cervix and no evidence of infection or fetal distress were randomized formally to receive prostaglandin E2 (3mg) gel or sterile K-Y Jelly intravaginally. Conservative expectant management was followed for the next 24 hours. The subsequent management of the labour followed departmental protocol. The women who received prostaglandin went into labour sooner and were delivered earlier but the duration of labour was not significantly different. There were no significant differences in other clinical outcomes. There was 1 case of uterine rupture in the prostaglandin group. We conclude that early intervention with prostaglandin E2 gel intravaginally confers no advantage compared with conservative management except for earlier confinement in this group of patients. PMID- 1586331 TI - Fetal arrhythmias: a 3-year experience. AB - Eight cases of fetal arrhythmia were seen over a 3-year period. Two had atrial and/or ventricular extrasystoles, 1 had complete atrioventricular block and 5 had tachyarrhythmias--3 supraventricular tachycardia, 1 atrial flutter and 1 ectopic atrial tachycardia. All had structurally normal hearts. Nonimmune hydrops fetalis was the initial presentation in 3 of the 5 cases with tachyarrhythmias. There were 2 deaths--a stillbirth and a neonatal death, while 2 others required neonatal intensive care. The 6 survivors have remained well and are now off treatment. The diagnosis, careful assessment and management of a fetal arrhythmia may lead to a successful outcome. The complexity of the problems experienced may warrant early referral to a tertiary centre where the overall management of the mother, fetus and neonate, may be undertaken. PMID- 1586332 TI - Prospective study of the quality of survival of infants with critical fetal reserve detected by antenatal cardiotocography. AB - From 1981 to 1986 antenatal cardiotocographic monitoring was performed on 9,992 high-risk pregnancies selected from a total obstetrical population of 31,518 patients (31.7%). A critical fetal reserve pattern was detected in 89 patients (0.9%) whose pregnancies resulted in 68 surviving infants, 19 perinatal deaths and 2 sudden infant deaths. Since 47.4% of the infants who died in the perinatal period did so because of a related congenital malformation, such a defect should be excluded in the fetus with critical fetal reserve, by ultrasonography, before delivery (there is usually insufficient time for fetal karyotyping). Sixty-three (92.6%) of the surviving children were assessed at our Growth and Developmental Clinic and disabilities were detected in 16 (25.4%); however, the disability was major in only 5, including 2 children with Down syndrome. The quality of survival of infants born from pregnancies complicated by critical fetal reserve was satisfactory as 60 of 63 children (95.2%) had neither a major disability related to intrauterine hypoxia identified by the cardiotocographic pattern, or had one likely to significantly interfere with their quality of life. Our results suggest that pregnancies can be continued until the cardiotocographic pattern becomes critical in order to gain fetal maturity, without compromise to the fetal brain. PMID- 1586333 TI - Prognosis in fetal cystic hygroma. AB - Axillary and lateral cervical fetal cystic hygromas in a fetus with normal karyotype are described. Fetal death at 25 weeks' gestation occurred. A literature review revealed that for cystic hygroma 42% of infants are 45XO, 38% have a normal karyotype, and 18% have trisomies. Prognosis is grim if the karyotype is abnormal or if hydrops or bilateral pleural effusions are present. Survival rate progressively improves with normal karyotype (27%), unilateral pleural effusion (40%), atypical location (56%), and resolution of cystic hygroma (71%). No single feature signifies 100% survival. The overall survival rate for fetal cystic hygroma is 10%. Prognosis remains guarded regardless of all other factors until the fetus reaches 26 weeks' gestation, after which time a 67% chance of ultimate survival can be expected. Only 42% of documented survivors were completely normal at follow-up. PMID- 1586334 TI - Endocervical Chlamydia trachomatis infection in pregnancy: direct test and clinico-sociodemographic survey of pregnant patients at the Port Moresby General Hospital antenatal clinic to determine prevalence and risk markers. AB - The prevalence of endocervical C. trachomatis infection in 181 consecutive antenatal clinic patients at the first attendance and who had not received antibiotic therapy in the previous 4 weeks, was 17.7%. The direct fluorescent antibody test was used for diagnosis. There was no significant clinical or sociodemographic factor which distinguished patients who tested positive from those who tested negative. PMID- 1586335 TI - Autologous blood donation for elective gynaecological surgery. AB - The utilization and effectiveness of a hospital autologous blood donation programme for elective gynaecological surgery at Ramathibodi Hospital during April 1, 1988-March 31, 1991 were analyzed. A total of 438 patients or 98% of eligible patients were enrolled into the programme. Each patient gave 1 unit of blood within 14 days of undergoing gynaecological surgery. The untoward effects observed in the programme were higher than those found in the regular donors. However, these were very mild. Nearly 90% of the participants used no homologous blood during their hospitalization, 8% used only their autologous blood, while 2% used additional homologous transfusion. The released autologous components were subsequently administered to other recipients. The patients' acceptance was excellent. Autologous blood donation is a safe, inexpensive and feasible procedure for transfusion treatment in elective gynaecological surgery especially in developing countries. PMID- 1586336 TI - Maximum effort in the management of ovarian cancer, including pelvic and para aortic lymphadenectomy. AB - Patients treated for ovarian cancer at the Mercy Hospital for Women, Melbourne over a 5 1/2 year period were studied with an emphasis on the need for lymphadenectomy. There were 80 patients identified with ovarian cancer. Forty patients underwent pelvic and/or para-aortic lymphadenectomy and 25 (62.5%) were found to have lymph node metastases, in 7 of the 40 women the lymphadenectomy resulting in upstaging of the disease. FIGO has adopted a surgicopathological approach to the staging of ovarian cancer and this requires lymphadenectomy to be performed. The importance of accurate staging in clinically early ovarian cancer and maximum surgical effort in advanced disease is discussed with particular regard to the place of lymphadenectomy. PMID- 1586337 TI - A study of women who appear to default from management of an abnormal Pap smear. AB - A study of nonattendance at a Dysplasia Clinic found that 20% of women who had an appointment in 1988 failed to attend the clinic during the next 18 months. Most of the nonattendance was among women who had previously been assessed at the Dysplasia Clinic. Only 6% of the nonattending women had cytological/histological evidence of CIN which remained untreated. If all women who did not default from attendance at the Dysplasia Clinic were correctly managed, then 1% of all women who have appointments made for the Dysplasia Clinic were potentially receiving inadequate management for lesions considered to have a precancerous potential. A questionnaire to the women who failed to attend these appointments identified pregnancy and seeking management elsewhere as the most commonly stated reasons for the nonattendance. PMID- 1586338 TI - Management of the psychosocial aspects of infertility. AB - There is a growing recognition of the place and importance of psychosocial factors in the infertility field. Counsellors, social workers, psychologists and others who work with the psychosocial dimensions are of relatively recent origin and as a consequence it is not uncommon for there to be confusion, sometimes conflict and often uncertainty between them and the more established health professionals. Knowledge, understanding and appreciation of the contributions of the staff involved is essential if the referral process is to be beneficial for the patients and less frustrating for the staff. Against this backdrop, the paper will seek to clarify some of the factors associated with recognizing and responding to the psychosocial aspects of infertility, highlight some points concerning teamwork between doctors and workers in the psychosocial field, and finally present a list of indicators which might be used as a guide in determining when to make a referral for psychosocial assistance. PMID- 1586339 TI - Born before arrival--uncovering the hazards. AB - In a retrospective case controlled study the demographic background and outcome of 193 mothers whose babies were born before arrival at hospital was compared to that of a control group who delivered within the maternity units of 2 teaching hospitals in Hong Kong. Mothers who delivered before arrival at hospital were significantly more likely to be single, to have received no antenatal care, to have an unplanned pregnancy, low family income and to come from a socially disadvantaged group such as Vietnamese refugees and illegal immigrants from China. Lacerations to the genital tract, postnatal anaemia and blood transfusions were more common in the study group. Results of cervical cytology and rubella status were available in significantly fewer of these mothers. They were more likely to be ambivalent about contraception and less likely to attend the postnatal clinic. The perinatal mortality and morbidity was significantly increased. PMID- 1586340 TI - Human menopausal gonadotrophins in the treatment of unexplained infertility. AB - Ninety one patients with unexplained infertility were treated with human menopausal gonadotrophin (HMG) and human chorionic gonadotrophin (HCG). The overall pregnancy rates were 29% per patient and 11% per cycle. In patients under the age of 37, the rates were 40% per patient and 15% per cycle. Many cycles (15%) were cancelled because of poor response to stimulation and by definition these women had normal cycles prior to stimulation. Within 1 year of ceasing HMG treatment, 9 patients had conceived spontaneously and another 4 conceived by GIFT. PMID- 1586341 TI - The effect of obesity on the outcome of successful surgery for genuine stress incontinence. AB - In a study of 190 patients with genuine stress incontinence, 91 patients were of normal weight, 66 overweight and 33 obese as determined by their Body Mass Index at the time of operation which was either a colposuspension (143) or a silastic sling insertion (47). Body mass index was found to significantly alter the outcome. PMID- 1586342 TI - The diagnostic value and patient acceptability of outpatient endometrial sampling with Gynoscann. AB - Endometrial sampling with Gynoscann was performed in the outpatient department in 70 women with abnormal vaginal bleeding prior to dilatation and curettage (D&C). Successful endometrial sampling was achieved in 62 (89%) patients; Of the samples obtained 44 (71.0%) were adequate for cytological assessment and 46 (74.2%) for histological assessment, compared to 80% of D&C samples being adequate for histological examination. In those patients in whom outpatient endometrial sampling was adequate, both the cytological and histological diagnosis agreed with the D&C. The outpatient endometrial sampling was well tolerated by the patients since the majority (89%) experienced either no or little pain. Vaginal bleeding following the procedure was minimal in all except 1 patient. Endometrial sampling with Gynoscann may be useful for endometrial assessment prior to commencement of hormonal therapy and hysterectomy. It is a potentially useful screening test for early detection of endometrial cancer in patients at risk. PMID- 1586344 TI - Ruptured ectopic pregnancy in an amenorrhoeic woman after transcervical resection of the endometrium. PMID- 1586343 TI - Headache following epidural analgesia. AB - Many headaches following epidural analgesia are a consequence of a dural tap having occurred. However, this is not always the case and careful evaluation is required. A case of postpartum headache caused by an intracerebral haemorrhage is presented. PMID- 1586345 TI - Bilateral ureteric obstruction due to recurrent endometriosis associated with hormone replacement therapy. PMID- 1586346 TI - Transitional cell carcinoma in a urethral diverticulum. PMID- 1586348 TI - Beware the obese patient for endometrial ablation. PMID- 1586347 TI - Cognitive and social influences on smoking behaviour during pregnancy. PMID- 1586349 TI - Possible conditioned stimulus pathway for classical eyelid conditioning in rabbits. I. Anatomical evidence for direct projections from the pontine nuclei to the cerebellar interpositus nucleus. AB - Wheat germ agglutinin and cholera toxin-conjugated horseradish peroxidase (HRP) were used to retrogradely and anterogradely trace connectivity between the lateral regions of the pontine nuclei and the anterior interpositus nucleus of the cerebellum in rabbits. Projections from the pontine nuclei were found to terminate in the anterior interpositus nucleus and the interpositus was found to send projections to the pontine nuclei. Projections from the nucleus reticularis tegmenti pontis, dorsal accessory inferior olive, and Larsell's lobule HVI of the cerebellum were also found to terminate in the interpositus nucleus and projections from the interpositus nucleus to the inferior olivary complex were observed. The projections from brain stem regions to the interpositus nucleus are discussed as possible pathways that are involved in classical eyelid conditioning. PMID- 1586350 TI - Postacquisition injection of tetrodotoxin into the parabrachial nuclei elicits partial disruption of passive avoidance reaction in rats. AB - The recent discovery that post-trial functional blockade of the parabrachial nuclei by intracerebral injection of 10 ng tetrodotoxin (TTX) disrupts acquisition of conditioned taste aversion (CTA) (Ivanova & Bures, 1990a,b) has prompted attempts to ascertain the role of this structure in other types of inhibitory learning. In Experiment 1, rats with implanted parabrachial cannulae were trained in a step-through avoidance task and received bilateral TTX (2 x 10 ng) immediately after the acquisition trial; they displayed significantly weakened avoidance of the shock compartment 2 days later. In Experiment 2, rats were anesthetized with pentobarbital (50 mg/kg) immediately after passive avoidance acquisition and received parabrachial TTX 15 min later; whereas anesthesia alone left the passive avoidance reaction (PAR) unaffected, TTX elicited similar disruption as in unanesthetized animals. In Experiment 3, TTX was injected in anesthetized animals 0, 1, 2, or 4 days after PAR acquisition. The amnesic effect was significant when the acquisition-TTX delay had been prolonged to 24 but not to 48 or 96 h. Since CTA is disrupted by reversible blockade of parabrachial nuclei and of the adjacent reticular formation elicited up to 4 days after acquisition (Ivanova & Bures, 1990b), PAR seems to be impaired to a lesser degree and for a shorter time than CTA by similar TTX treatment. PMID- 1586351 TI - The effects of reversible lidocaine-induced lesion of the tissue surrounding the anterior ventral wall of the third ventricle on drinking in rats. AB - The local anesthetic lidocaine (XILOCAINA), 2%, was injected into the tissue surrounding the anterior region of the third cerebral ventricle (AV3V) of the rat, through a permanently implanted cannula, to produce a temporary and reversible disruption of the nervous connections of this area with other cellular nuclei while leaving the vascular connections intact. Following 24 h water deprivation, lidocaine was injected, and after 20 min water intake decreased; subsequently, the lidocaine-injected rats behaved similarly to control rats injected with artificial cerebrospinal fluid. Osmotic drinking was not affected. Prolonged adipsia or hyperdipsia did not occur. In nondeprived rats, lidocaine prevented angiotensin II-induced drinking. Following 24 h sodium depletion by peritoneal dialysis, lidocaine decreased the specific sodium appetite by 50% in animals with different levels of body sodium depletion. The data indicate that the integrity of the neural tissue of the AV3V is essential for a correct body water-salt regulation. Temporary "ablation" with lidocaine, which blocked neural activity but maintained the blood supply, produced responses different from most of those reported after electrolytic lesions. Therefore, lidocaine may be used as a tool to assess the response of this neural tissue to body fluid regulation. PMID- 1586352 TI - Lesions of the rat postsubiculum impair performance on spatial tasks. AB - Previous studies have identified a population of neurons in the postsubiculum that discharge as a function of the rat's head direction in the horizontal plane (Taube, Muller, & Ranck, 1990a). To assess the contribution of these cells in spatial learning, Long-Evans rats were tested in a variety of spatial and nonspatial tasks following bilateral electrolytic or neurotoxic lesions of the postsubiculum. Compared to unlesioned control animals, lesioned animals were impaired on two spatial tasks, a radial eight-arm maze task and a Morris water task, although the performance scores of both lesion groups improved over the course of behavioral testing. In contrast, lesioned animals were unimpaired on two nonspatial tasks, a cued version of the water maze task and a conditioned taste-aversion paradigm. In addition, lesioned animals showed transient hyperactivity in an open-field activity test. These results support the concept that neurons in the postsubiculum are part of a neural network involved in the processing of spatial information. PMID- 1586353 TI - Shared maternal influences in the development of high blood pressure in the spontaneously hypertensive (SHR) and Dahl salt-sensitive (SS/Jr) rat strains. AB - The influence of maternal environment on the development of high blood pressure in spontaneously hypertensive (SHR) and Dahl salt-sensitive (SS/Jr) rats was examined using the technique of reciprocal cross-fostering. Previous experiments from this laboratory demonstrated that adult blood pressures of the SHR and SS/Jr strains were significantly attenuated when hypertensive-strain pups were fostered to a dam of the respective normotensive control strain during the preweaning period. In this study, SHR and SS/Jr pups were assigned to either a cross fostered (fostered to a dam of the opposite hypertensive strain) or control reared condition within 24 h of birth. Adult resting blood pressures were similar in control and cross-fostered SHR rats and in control and cross-fostered SS/Jr rats. Heart rates and heart, adrenal, and kidney weights were also similar in control and cross-fostered rats of each strain. However, body weights of SHR rats reared by an SS/Jr dam were somewhat lower compared to control-reared SHR rats. These data indicate that the maternal environments provided by SHR and SS/Jr mothers are similar in some way such that they permit the development and full expression of the hypertensive phenotype in both same-strain and opposite-strain pups. PMID- 1586354 TI - CGS 5649 B, a new compound, reverses age-related cognitive dysfunctions in rats. AB - CGS 5649 B improves the learning performance of aged rats in a one-way active avoidance situation. If, under reversed conditions, treated aged rats are also tested for passive avoidance, they show "place learning," which our findings have demonstrated to be typical of young rats. The effects of the substance are not confined to these experimental models nor are they species specific: it also facilitates passive avoidance in mice and social learning in rats. The compound is effective if administered before or immediately after the learning trial. PMID- 1586355 TI - Stimulus control of predatory behavior in the brown tree snake (Boiga irregularis). IV. Effect of mammalian blood. AB - Brown tree snakes (Boiga irregularis) from Guam were exposed to mammalian (Rattus norvegicus) blood on cotton-tipped applicators. Water and other control substances were similarly presented. All trials lasted 60 s, and the dependent variable was the number of tongue flicks emitted by the snake during the trial. In five experiments, B. irregularis responded with greater numbers of tongue flicks to blood than to control substances. This is the first study to reveal an ophidian response to internal chemicals of potential prey organisms. PMID- 1586356 TI - Delayed-onset sensitization emerges after dishabituation in developing Aplysia. AB - A recent study of the development of nonassociative learning in the siphon withdrawal reflex of Aplysia showed that dishabituation (facilitation of an habituated response) and sensitization (facilitation of a nonhabituated response) emerge according to different developmental timetables: dishabituation precedes sensitization by approximately 60 days (Rankin & Carew, 1988). Both forms of facilitation of the reflex were observed within 90 s of an electrical shock to the tail. However, more recent work by Marcus and colleagues (1988) in adult animals revealed that sensitization can have a delayed onset of 20-30 min after a strong tail shock. Since the developmental study of Rankin and Carew (1988) only tested the reflex for 10 min after tail shock, it is possible that sensitization was in fact present at earlier developmental stages, but was undetected. To examine this question, in the present study we utilized a longer (40-50 min) post shock observation period to determine whether delayed-onset sensitization is exhibited in juvenile Aplysia, and if so, when it is expressed during development. In our first experiment, we found that Early Stage 12 juveniles (80 95 days after metamorphosis) showed significant delayed-onset sensitization 30-50 min after a strong tail shock. In a second experiment, we found that delayed onset sensitization was absent in Stage 11 animals (20-70 days after metamorphosis). Thus delayed-onset sensitization emerges in Early Stage 12. The fact that the birthdate of delayed-onset sensitization is at least 30 days after that of dishabituation (Rankin & Carew, 1987, 1988) supports the hypothesis that these two forms of nonassociative learning may have at least partly different underlying mechanisms. PMID- 1586358 TI - The reduction of claustrophobia--I. AB - The purpose of this study was to investigate the process of change during three interventions for claustrophobia, with particular reference to cognitive changes. Forty-eight participants, recruited from the community through the local media, were randomly assigned to one of four groups: pure exposure, exposure to the sensations of anxiety (interoceptive exposure), modification of negative cognitions, or a control group. All interventions were given over three sessions. The exposure group proved superior to the control on a wide range of measures. In the cognitive group, scores of reported fear and panic, declined significantly. The interoceptive group made some modest gains. An analysis of the timing of fear reduction and of treatment generalization, provides some indications of the mechanism of change. PMID- 1586357 TI - Behavioral response of altricial and precocial rodent fetuses to acute umbilical cord compression. AB - Norway rat fetuses (Rattus norvegicus) exhibit a stereotypic behavioral response when the umbilical cord is experimentally compressed with a vascular clamp. In this study, the development of the fetal behavioral response to cord compression was compared in altricial and precocial rodents, which differ markedly in neural and motor maturity at the time of birth. Both altricial and precocial species showed some form of behavioral response to umbilical cord compression. Fetuses of two altricial species, Norway rats and Mongolian gerbils (Meriones unguiculatus), expressed hyperactivity in response to cord compression throughout the last third of gestation. In contrast, precocial cotton rats (Sigmodon hispidus) and spiny mice (Acomys cahirinus) did not respond to cord compression until relatively late in gestation. Thus, altricial and precocial species do not express the cord compression response during comparable periods of neural development: precocial species are much more mature at the earliest expression of this behavior than altricial species. These findings are consistent with the interpretation that the cord compression response is a behavioral adaptation that can promote survival of the fetus in utero. PMID- 1586359 TI - Interpretation of bodily symptoms in hypochondriasis. AB - Although it has been suggested that hypochondriasis is caused by the misinterpretation of innocuous bodily sensations, support for this hypothesis rests largely upon uncontrolled self-report. We investigated the interpretation of ambiguous bodily sensations in three experiments using separate samples of non clinical subjects differing in level of hypochondriacal concern. Results confirmed that subjects with high hypochondriacal concern endorse more thoughts about illness interpretations of bodily sensations, but reported thought content resembled 'catastrophic' rather than the 'non-emergency' thoughts suggested by Warwick and Salkovskis (Hypochondriasis. Behavior Research and Therapy, 28, 105 117, 1990). Presence of an interpretive bias was further supported in a study of recognition bias for disambiguated versions of ambiguously threatening sentences, although this applied as much to social as to illness threats. A final experiment failed to support the hypothesis of an automatic inference bias, but did show that subjects with high hypochondriacal concern were quicker to correctly identify previously exposed illness words. Thus, reported thoughts are consistent with catastrophic interpretations of common bodily sensations, but interpretive bias may not be limited to illness threat. However, high hypochondriacal subjects do show a more specific enhanced perceptual sensitivity to illness cues, which may play a role in maintaining their concern with bodily symptoms. PMID- 1586360 TI - Cue-exposure vs self-control in the treatment of binge eating: a pilot study. AB - From a recent theory on the learned nature of craving responses and binge eating, it follows that craving will extinguish when the CS-US bond is broken by prolonged exposure to the cues predicting excessive food intake with response prevention. The present authors treated six obese bulimics with cue exposure and response prevention. Six other patients learned to avoid or escape the binge related cues with the aid of self control techniques. Although both treatments appeared to be effective in reducing the binge frequency, a most remarkable finding of the present study is that all patients treated by cue exposure were abstinent, directly after treatment and during the 1 yr follow-up. In contrast to the 100% binge-free subjects treated by cue exposure, self control techniques and relapse prevention led to abstinence in merely 33% of the subjects. PMID- 1586361 TI - Body size perception and body satisfaction in restrained and unrestrained eaters. AB - In 21 restrained and 20 unrestrained eaters body size perception was measured using the video distortion technique (VDT), the image marking procedure (IMP) and the kinesthetic size estimating apparatus (KSEA). Body satisfaction was assessed by questionnaires (Body Shape Questionnaire, Dieting scale of the Eating Attitudes Test). Restrained eaters showed no systematic over- or underestimation of the body size but less perceptual accuracy (in VDT and KSEA). Furthermore, they were clearly more dissatisfied with their bodies than unrestrained eaters. Both findings were unrelated to each other. In both groups depressive mood or thoughts seemed to be associated with body dissatisfaction but not with body size misperception. Objective body measures (body mass index, body fat content) were not related to either body size perception or body satisfaction. The findings suggest that a perceptual uncertainty in regard to body size (either for visual or for somatosensory aspects) has already developed in restrained eaters, which may constitute a predisposition for more overt forms of body size misperception as found in eating disorder patients. PMID- 1586362 TI - Panic symptoms in asthma and panic disorder: a preliminary test of the dyspnea fear theory. AB - Ley's (Behaviour Research and Therapy, 27, 549-554, 1989) dyspnea-fear theory was tested on three groups of subjects: 10 with panic disorder, 24 with asthma, and 12 who were nonanxious and nonasthmatic, using measures of pulmonary function, muscle tension; and self-report measures of generalized anxiety, dyspnea, and psychopathology. Results are supportive of dyspnea-fear theory for asthmatics but not for individuals with panic disorder. Differences between groups on panic/fear measures were explained by a combination of general anxiety and dyspnea. Within group regression analyses showed that only generalized anxiety symptoms contributed significantly to scores on the Asthma Symptom Checklist scale of panic/fear within the panic disorder group; while only dyspnea contributed to panic/fear among asthmatics. Additional results show that panic disorder subjects performed normally on pulmonary function tests but reported respiratory symptoms as severe as did asthmatics. Compared with normal subjects, both patient groups displayed lower correlations between self-rated symptoms of bronchoconstriction and objective pulmonary measures. Panic disorder subjects showed a negative relationship between pulmonary function and hyperventilation symptoms, suggesting a heightened sensitivity to, and discomfort with, sensations associated with normal pulmonary function. Asthmatics displayed a significant relationship between degree of airway obstruction and both trapezius surface EMG and ratings of hyperventilation symptoms. PMID- 1586363 TI - Cognitive intrusions in a non-clinical population. II. Associations with depressive, anxious, and compulsive symptoms. AB - The relationships between experimental dimensions of cognitive intrusions and depressive, anxious, and compulsive symptoms were studied among 125 university students. The students completed a questionnaire describing and evaluating seven cognitive intrusions and inventories of depressive, anxious, and compulsive symptoms. Principal component factor analysis on the 14 cognitive intrusion questionnaire dimensions identified five factors that were interpreted as general distress, evaluation, control, diversity and attention. Hierarchical regression analysis showed that effortful strategies in response to cognitive intrusions, general distress and diversity were predictors of both Beck Depression and Beck Anxiety Inventory scores. The evaluation factor consisting of perceived responsibility, disapproval and guilt ratings was also associated with depression and was the only significant predictor of Compulsive Activity Checklist scores. The control factor, consisting of items describing successful application of response strategies, was negatively related to BAI scores. The results are discussed as providing support for Salkovskis' formulation of obsessive compulsive disorder. PMID- 1586364 TI - Comparison of positive and negative intrusive thoughts and experimental investigation of the differential effects of mood. AB - The similarity between positive and negative intrusive thoughts is considered for both recently occurring, personally relevant intrusions and for the same intrusions occurring during an experimental task involving self-monitoring. The results indicate that positive and negative intrusions differ in most respects. There was evidence that increasing the frequency of negative thinking is associated with a deterioration of mood. In a subsequent experiment, induced happy and sad moods were shown to differentially affect frequency of intrusions in a fashion consistent with mood congruency effects previously found in experiments on the effect of mood on memory. The implications of these findings for disorders involving the experience of intrusive thoughts such as OCD and depression are discussed. PMID- 1586365 TI - Are insomniacs sleepy during the day? A pupillometric assessment. AB - A biodevelopmental model of insomnia is articulated specifying coordinated nighttime (disturbed sleep pattern) and daytime (no excessive daytime sleepiness) characteristics defining an insomnoid classification in at-risk groups: short sleepers and older adults. Pupillometry is proposed as a useful means of discriminating degree of daytime sleepiness to aid in the differential diagnosis of insomnia and insomnoid states, and the present study tested the discriminative validity of this approach. Noninsomniac (n = 34) and insomniac (n = 29) college students submitted to four 10 min pupillometry sessions tracking daytime sleepiness from morning arising to bedtime. Pupil diameter proved to be an able discriminator of these two groups though substantial overlap of the two distributions was also noted. The results supported the sensitivity of pupillometry in detecting daytime sleepiness, but yielded alternative interpretations. We observed statistical differentiation in insomniac and noninsomniac daytime sleepiness, but substantial, functional overlap between these groups. Assessment and treatment implications arising from the biodevelopmental model were hypothesized. PMID- 1586366 TI - Physiological reactivity to stressors in irritable bowel syndrome patients, inflammatory bowel disease patients and non-patient controls. AB - Irritable Bowel Syndrome (IBS) patients were compared with Inflammatory Bowel Disease (IBD) patients and non-patient controls on four separate physiological measures (heart rate, finger-tip temperature, skin resistance level, and forehead EMG) for their physical reactivity to 'laboratory stressors'. It was predicted that the IBS patients would respond to these stressors with more physiological reactivity than the two other groups. There were initial basal differences among the groups on heart rate and finger-tip temperature: in general, the IBS patients had lower basal heart rates and the non-patient controls had lower finger-tip temperatures. These findings are contrary to the previous body of literature regarding possible sympathetic nervous system (SNS) arousal states in the IBS patient. The results also indicated IBS patients were not significantly different than the IBD patients or the non-patient controls in their reactivity to stressors. Previous literature has suggested that IBS in their reactivity to stressors. Previous literature has suggested that IBS patients have an enhanced SNS arousal or an SNS mediated reactivity to environmental stressors, our current study has not found these results. PMID- 1586367 TI - Cognitive-behavioural approaches in the treatment of hypochondriasis: six single case cross-over studies. AB - This study evaluates a cognitive and a behavioural treatment protocol for hypochondrical complaints. In a cross-over design, six patients with a primary diagnosis of hypochondriasis were treated. Three of them first received a block of behavioural therapy (exposure in vivo and response prevention), followed by a block of cognitive therapy. The other three patients were first treated with cognitive therapy followed by behavioural therapy. The results were promising: four patients made significant improvements. The behavioural therapy sessions appeared to account more often for improvement than did the cognitive sessions. The sequence of behavioural therapy followed by cognitive therapy tended to be more successful than the other way around. The results of these six case studies suggest that exposure in vivo with response prevention and cognitive therapy may both be useful in the treatment of hypochondriasis. A journal controlled study is recommended. PMID- 1586368 TI - Dissimulation and the sex difference in self-assessed fears: a brief note. AB - Since the publication of the first findings with a Fear Survey Schedule over five decades ago, there have been no published studies examining the extent of overlap of factorially-derived robust dimensions of irrational fears with social desirability or dissimulation. Due to measurement problems associated with the use of individual fear items or general fear measures, the findings reported to date are relatively meaningless. In the present study, community volunteers were administered the Fear Questionnaire and the Eysenck Personality Questionnaire-Lie scale, the correlation between both measures determined, and the influence of the Lie scores on the sex difference in self-assessed fears examined. Neither in males nor in females were Agoraphobic and Social fears significantly correlated with dissimulation. Significant associations reflecting small effect sizes were obtained in both samples between Blood-injury fears and Lie scores. Only the sex difference in Blood-injury fears was meaningfully affected by dissimulation: the usual finding of higher mean scores for females was obtained only after controlling for the influence of Lie scores. The importance of taking the research and practical implications of the findings with respect to the Blood injury fears dimension seriously, despite the small magnitudes of the relevant data, was emphasized, as was the need for further studies in this area. PMID- 1586369 TI - Sorting of proteins to the vacuoles of plant cells. AB - The secretory system of plant cells sorts a large number of soluble proteins that either are secreted or accumulate in vacuoles. Secretion is a bulk-flow process that requires no information beyond the presence of a signal peptide necessary to enter the endoplasmic reticulum. Many vacuolar proteins are glycoproteins and the glycans are often modified as the proteins pass through the Golgi complex. Vacuolar targeting information is not contained in glycans as it is in animal cells; rather, targeting information is in polypeptide domains as it is in yeast cells. Several such domains have now been identified, but these show little or no amino acid sequence homology. We discuss the possibilities that targeting of protein to plant vacuoles may involve receptors as well as aggregation of protein at low pH. PMID- 1586370 TI - The ageing pineal gland and its physiological consequences. AB - Melatonin, the chief hormone of the pineal gland, is produced and secreted into the blood in a circadian manner with maximal production always occurring during the dark phase of the light:dark cycle. Whereas the 24h rhythm of melatonin production is very robust in young animals including humans, the cycle deteriorates during ageing. The rhythm of melatonin can be substantially preserved during ageing by restricting the food intake of experimental animals; this same treatment increases the life span of the animals. The exogenous administration of melatonin to non-food restricted animals also reportedly increases their survival. Moreover, melatonin has been shown to have immunoenhancing effects and oncostatic properties. The implication of these studies is that melatonin may have both direct and indirect beneficial effects in delaying ageing processes or it may retard the development of processes (e.g., immunodeficiency and tumor growth) which contribute to a reduced life span. PMID- 1586371 TI - Regulatory mechanisms for ras proteins. AB - The proteins encoded by the ras proto-oncogenes play critical roles in normal cellular growth, differentiation and development in addition to their potential for malignant transformation. Several proteins that are involved in the control of the activity of p21ras have now been characterised. p120GAP stimulates the GTPase activity of p21ras and hence acts as a negative regulator of ras proteins. It may be controlled by tyrosine phosphorylation or association with tyrosine phosphorylated proteins. The neurofibromatosis type 1 (NF 1) gene also encodes a potential GTPase activating protein which is likely to be subject to a different control mechanism. Guanosine nucleotide exchange factors for p21ras have now been identified: these may be positive regulators of ras protein function. It appears that p21ras is subject to rapid regulation by several distinct mechanisms which are likely to vary in different cell types; the ras proteins are thereby able to act as very sensitive cellular monitors of the extracellular environment. PMID- 1586372 TI - Why do cancer cells metastasize into particular organs? AB - Metastatic spread of tumor cells is one of the most common causes of death in cancer patients. Therefore, elucidation of the molecular mechanisms that underlie the formation of metastatic colonies has been one of the major objectives of cancer research during the last two decades. In this review we will mainly discuss the mechanisms that cause a malignant cell to grow at a given site rather than at other possible sites, taking into account experimental and clinical evidence published on the subject. As a whole this evidence tends to confirm the hypothesis that organ-specific colonization by malignant cells often follows very specific and close interactions between the cancer cell and the target organ, either in terms of specific cellular adhesion or growth promotion. In this paper we would like to underscore the fact that cellular adhesion, either specific or unspecific, is a necessary but, by itself, insufficient condition for the development of metastases. It is the ability of the tumor cells to grow at the site where they arrested that ultimately determines whether a metastatic colony develops or fails to develop at that site. PMID- 1586373 TI - Cardiovascular activities of the new potent and long-lasting antihypertensive calcium entry blocker (+-)-3-ethyl,5-methyl,2- ([2-(formylamino)-ethyl]- thiomethyl)-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicar box ylate. AB - BBR 2160 ((+-)3-ethyl,5-methyl,2-([2-(formylamino)-ethyl]- thiomethyl)-6-methyl-4 (3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarb oxy late, CAS 118587-22-7) is a new calcium entry blocker (CEB) which completely displaces 3H-nitrendipine from binding sites, is 10 times more potent than amlodipine (A) and equiactive with nifedipine (N). On the rat aorta contracted by 10 mmol/l Ca++, or 45 mmol/l K+, BBR 2160 shows higher CEB activity than N and A, achieving the maximum effect on voltage operated channels-induced contractions in 6 h, while N takes about 2 h. BBR 2160, N and A negatively affect the chronotropism on spontaneously beating, and inotropism on electrically driven guinea pig atria, respectively. In vitro BBR 2160 has marked vasoselectivity. Administered orally to conscious hypertensive rats (SHR) and renal hypertensive dogs (RHD), it caused a dose dependent reduction in systolic blood pressure with a relatively slow onset, peak effect at 3-6 h and duration over 6 h. BBR 2160 and A have more pronounced activity on SHR than on normotensive rats (NR) (ED20 NR/SHR 3.3 for both compounds), while the antihypertensive and hypotensive activities of N are in the same dose-range (ED20 NR/SHR 1.3). No tolerance develops to the antihypertensive effects of BBR 2160 after five days' dosing up to 3.2 mg/kg in SHR and 1 mg/kg in RHD. In instrumented conscious normotensive dogs BBR 2160, N and A mostly lower diastolic blood pressure and total peripheral resistance, and do not increase total oxygen consumption.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586374 TI - [Pharmacokinetics of low-dose isosorbide dinitrate and metabolites after buccal or oral administration]. AB - The kinetics of isosorbide dinitrate (ISDN; CAS 87-33-2) and its metabolites isosorbide-5-mononitrate (IS-5-MN) and isosorbide-2-mononitrate (IS-2-MN) were examined after buccal and oral administration of 5 mg ISDN. Twelve healthy volunteers were included in a randomized cross-over study. The mean dose corrected AUCs for total nitrate in serum after the two different preparations were in the same range. The relative bioavailability of ISDN applied buccally, however, was more than twice that after oral application. The metabolism of ISDN differed depending on the route of administration, where the AUC-ratios ISDN: IS 2-MN: IS-5-MN were 1:2.7:19.4 after buccal and 1:5.7:53.4 after oral application respectively. The absorption rate constants Ka for ISDN and the MRT after buccal and oral application did not differ significantly. The same holds for the mean residence time. PMID- 1586375 TI - [Biological availability and pharmacodynamics following single oral administration or three different sustained-release isosorbide-5-mononitrate dosage forms]. AB - The bioavailability of 3 different commercial available isosorbide mononitrate (IS-5-MN; CAS 16051-77-7) 40 mg slow-release preparations (A, B and reference formulation C) was determined after oral application to 18 healthy volunteers in a randomized cross-over study. The AUC after C (26.9 mumol/l x h) was not significantly different from that for A (25.1 mumol/l x h) and B (26.0 mumol/l x h). The corresponding 95% confidence intervals were within the limits of 80-120%. Maximal plasma concentrations (Cmax) for C (1.90 mumol/l), A (1.91 mumol/l), and B (2.05 mumol/l) were obtained at (tmax) 5.72 h, 4.94 h and 4.72 h, respectively. The 95% confidence intervals for Cmax and tmax were within the prescribed limits of 70-130%. Mean residence times (MRT) 10.5 h (C), 10.3 h (A), and 10.1 h (B) and plateau-times (duration over which the plasma concentration greater than 0.524 mumol/l) 17.8 h (C), 17.1 h (A), and 17.0 h (B) were not significantly different. It is concluded that the test preparations A and B are bioequivalent to reference C. Systolic blood pressure and heart rate, easily measurable indeces of the pharmacodynamic effects, showed no significant differences between the 3 preparations. In agreement with recently published data, plasma concentrations above 1.5 mumol/l did not result in a further reduction of systolic blood pressure, but were associated with a further marked elevation in heart rate. PMID- 1586376 TI - Comparative bioavailability of two tablet preparations of diltiazem in healthy volunteers. AB - Comparative bioavailability of two formulations of diltiazem (Dilzene, CAS 42399 41-7), a calcium antagonist, was evaluated on 10 healthy volunteers (5 males and 5 females) in a cross-over study. A single dose of 120 mg of diltiazem was administered to the volunteers in the form of either two 60-mg tablets or a 120 mg controlled-release tablet. Plasma concentrations of diltiazem over a 24-h time interval were determined by HPLC analysis. Results of this investigation demonstrate that the controlled-release formulation of diltiazem has a lower Cmax value when compared to the 60 mg conventional tablet formulation, but a longer tmax and a superimposable AUC. PMID- 1586377 TI - Effects of the new antiplatelet agent 2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine on platelet aggregation and thrombosis in experimental animals. AB - Antiplatelet and antithrombotic effects of KC-764 (2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) were studied. KC 764 inhibited arachidonic acid (AA)- and collagen-induced platelet aggregation with IC50s of 1.0 x 10(-8)-2.8 x 10(-7) mol/l for humans, rabbits, guinea pigs and dogs, and IC50s of 3.9 x 10(-6)-3.7 x 10(-5) mol/l for mice and rats in vitro. KC-764 inhibited AA- and collagen-induced aggregation with ID50s of 0.04 0.09 mg/kg p.o. in rabbits and dogs, and ID50 of 13.0 mg/kg p.o. in rats. These antiaggregatory activities of KC-764 were stronger than those of acetyl-salicylic acid (ASA), indometacin, cilostazol and ticlopidine. KC-764 inhibited the production of thromboxane B2 (TXB2) in rabbit platelet microsomes, washed platelets and reconstituted platelet rich plasma (RPRP) with IC50s of 2.9 x 10( 6) mol/l, 2.8 x 10(-7) mol/l and 4.3 x 10(-8) mol/l, respectively. The in vitro inhibitory activity of KC-764 on AA-induced platelet aggregation was more potent when RPRP was used rather than washed platelet suspension containing 30% rabbit plasma. ASA did not show such an augmentation. KC-764 prevented collagen- and AA induced thrombosis at more than 1 mg/kg p.o. and more than 0.1 mg/kg i.v. in mice and rabbits. KC-764 showed the wider margin of dose between antiplatelet action and prolongation of bleeding time in rabbits than ASA and indometacin. These results indicated that KC-764 was a potent antithrombotic drug to prevent TXB2 production and less possible to induce untoward actions as compared with ASA or indometacin. PMID- 1586378 TI - Protective effect of the new antiplatelet agent 2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine on myocardial damage due to coronary occlusion and reperfusion in rabbit. AB - The effects of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5 a]pyridine, CAS 94457-09-7) on infarct size, myeloperoxidase (MPO) activity and plasma prostanoid levels were studied using coronary artery occlusion (1 h) reperfusion (3 h) model in rabbits, comparing with acetylsalicylic acid (ASA). Myocardial infarct size, MPO activity in the infarcted region and plasma glutamate oxalo-acetate transaminase, lactate dehydrogenase and creatine kinase were significantly suppressed by treatment with KC-764 (2 mg/kg i.v.), but not by ASA (10 mg/kg i.v.). KC-764 completely depressed the increase in plasma TXB2 level during occlusion-reperfusion with a little influence on plasma 6-keto-PGF1 alpha. Thus, the ratio of 6-keto-PGF1 alpha to TXB2 levels was increased by KC 764. On the other hand, ASA treatment depressed both plasma TXB2 and 6-keto-PGF1 alpha levels to the same extent. The in vitro study with guinea-pig neutrophils showed that KC-764 reduced the chemotaxis induced by formyl-methionyl-leucyl- phenylalanine at 3 x 10(7)-3 x 10(-6) mol/l, while ASA did not influence the neutrophil chemotaxis. These results suggest that KC-764 may salvage the damaged ischemic myocardium by the selective inhibition of TXA2 synthesis and the suppression of leukocyte migration. PMID- 1586379 TI - Antiplatelet effects of 2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5 a]pyridine in relation to its disposition in rats, rabbits and dogs. AB - KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was evaluated for the inhibition of platelet aggregation and prostanoid production in rats, rabbits and dogs, comparing with acetylsalicylic acid (ASA). Correlations between the inhibitory action and plasma concentration of KC-764 were examined in rabbits. KC-764 was 200 times more potent than ASA in inhibiting collagen-induced rabbit platelet aggregation and TXA2 production in vitro. KC-764 exhibited more selective inhibition of TXA2 production over PGI2 production than ASA. The ratio of IC50's of PGI2 production to TXA2 production of KC-764 was 175 in rats, 72 in rabbits and 65 in dogs, respectively. Such a selectivity was also confirmed ex vivo. The depression of plasma TXB2 levels was well correlated with the ex vivo antiaggregatory activity in rabbits at oral doses of KC-764 ranging from 0.02-1.5 mg/kg. The concentrations/in vitro inhibitory activity relationship was expressed by a sigmoid Imax model equation. The ex vivo antiplatelet activity and prostanoid production were reconstructed with Imax model equation using the simulated plasma drug concentrations and in vitro Imax model parameters in all animals. The relationship could be applied for the prediction of the inhibitory activity of KC-764 in humans. These results indicate that KC-764 is a potent, selective and reversible antiplatelet drug, being different from ASA. PMID- 1586380 TI - Identification of urinary metabolites of 2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in rat, rabbit and dog. AB - The metabolism of KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo[1,5 a]pyridine, CAS 94457-09-7) in rat, rabbit and dog was studied. The urine of animals dosed with 14C-KC-764 was extracted with ethyl acetate after treatment with beta-glucuronidase and arylsulfatase. The metabolites were purified by TLC and HPLC from the extract. Unchanged KC-764 and 16 metabolites were isolated and their structures were identified or proposed by NMR and MS spectrometry. The metabolism of KC-764 took place by the oxidation of the tetrahydropyridine ring, 6,7-position and 2-methyl group of the pyrazolopyridine ring, and their combinations. The oxidation of the tetrahydropyridine ring was predominant in dog, whereas the oxidation of the pyrazolopyridine ring was more important in rabbit. Rat produced the various metabolites by their combination. 6-Oxo and 6 ureido derivatives of the tetrahydropyridine ring were common major metabolites in all animal species studied. PMID- 1586381 TI - Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in laboratory animals. AB - KC-764 (2-methyl-3-(1,4,5,6-tetrahydronicotinoyl)pyrazolo [1,5-a]pyridine CAS 94457-09-7) and its metabolites in serum and urine were determined after intravenous and oral administration in mice, rats, rabbits and dogs at a dose of 5 mg/kg. KC-764 was rapidly eliminated from serum in all species. The biological half-lives of unchanged KC-764 after intravenous administration in mice, rats, rabbits and dogs were 1.31, 0.29, 1.94 and 1.20 h, respectively. 2-Methyl-3 (1,4,5,6-tetrahydro-6-oxonicotinoyl)pyrazolo-[1,5-a]pyr idine was a common major metabolite in serum of all species, although 6,7-dihydro-6,7-dihydroxy-2-methyl-3 (1,4,5,6- tetrahydro-6-oxonicotinoyl) pyrazolo-[1,5-a]pyridine (M-8) was more abundant in rabbits. Urinary recovery of unchanged KC-764 was as low as 0.4-2.2% in all species. The major urinary metabolite was 2-methyl-3-(1,4,5,6-tetrahydro-6 ureidonicotinoyl)pyrazolo-[1,5-a] pyridine in mice, rats and dogs, but M-8 was in rabbits. KC-764 was rapidly and well absorbed by oral administration, and extensively metabolized in all species tested. PMID- 1586382 TI - Pharmacokinetics of the new antiplatelet agent 2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine in human subjects. AB - The pharmacokinetics of KC-764 (2-methyl-3-(1,4,5,6 tetrahydronicotinoyl)pyrazolo[1,5-a]pyridine, CAS 94457-09-7) was studied in healthy male adult volunteers after single ascending oral dose and multiple dosing for 7 days. Serum KC-764 concentration attained the peak in 1 h and declined with a half-life of about 2 h at a single oral dose of 5, 10, 20 and 40 mg. No dose dependent pharmacokinetics of KC-764 was demonstrated. Three metabolites were detected in serum, but their concentrations were lower than that of KC-764. 48-h urinary recoveries after single doses were 41.6-46.6% of dose, not being dose-dependent. Urinary recovery of unchanged KC-764 was 1.1-1.6% of dose. Three metabolites were present in greater amount in urine than unchanged KC 764 and two metabolites were less than KC-764. There was little daily variation of serum concentrations and urinary excretion of KC-764 and its metabolites in the multiple dosing (20 mg twice a day) study. The daily and total urinary recovery were same as those after single doses. Food reduced Cmax and tended to delay tmax, but did not influence AUC0----infinity and urinary recovery. Serum protein binding of KC-764 was about 60%, being not dependent on total serum concentration. PMID- 1586383 TI - Synthesis and anti-HIV-1 activity of N-hydroxy-N1-aminoguanidines. AB - The synthesis of 13 new Schiff bases of N-hydroxy-N1-aminoguanidines starting from thiosemicarbazide are reported. These new derivatives were for the first time tested against infection by the Human Immunodeficiency Virus Type 1 (HIV-1) using the human T-lymphocyte cell line. Four N-hydroxy-N1-aminoguanidines exhibited HIV-1 inhibition in the micromolar range. The most active compound, [1 (1'-chloro-2'-hydroxy-3'-methoxybenzylidene)amino]-3-hydroxy guanidine inhibited HIV-1 by 96% at 10 micrograms/ml concentration. All the derivatives exhibited substantial cytotoxicity at 320 micrograms/ml concentration. The results indicate that the activity against HIV-1 increases with increasing hydrophobicity and substituents with electron-donating properties. PMID- 1586384 TI - Synthesis and antipseudomonal activities of some ofloxacin esters as prodrugs. AB - Three new ofloxacin esters have been synthesized as prodrug by the reaction of ofloxacin (CAS 82419-36-1) with chloromethylacetate, 1-chloroethylacetate and 1 chloroethylethylcarbonate in acetonitrile. The structures of the compounds have been elucidated by UV, IR, 1H-NMR, Mass spectra and elementary analysis. In vitro activities of these compounds against clinical isolates of various Pseudomonas aeruginosa species have been determined by microtiter tube dilution method, and octanol/water partition coefficients and pH dependent hydrolysis rates have been investigated in comparison with ofloxacin. PMID- 1586385 TI - Effect of food on absorption and hydrolysis of erythromycin acistrate. AB - Effect of food on absorption of erythromycin acistrate (2'-acetyl erythromycin stearate, Erasis; CAS 96128-89-1) was studied in 14 healthy volunteers in a randomized cross-over design. The subjects were given 400 mg erythromycin acistrate enteric coated tablets b.i.d. for 4 days. On the 1st and 4th days the tablets were taken after an overnight fast or immediately after a light or a heavy breakfast. Erythromycin (E), 2'-acetyl-erythromycin (2AE), anhydroerythromycin and anhydro-2'-acetyl-erythromycin concentrations in plasma were analyzed chemically by HPLC. After a single dose the lag time of absorption (tlag) was significantly longer after both types of breakfasts as compared to fast. The tmax of E and 2AE were also somewhat delayed by food although tmax of 2AE after a heavy breakfast only differed statistically significantly from that of the fasting state. Food significantly delayed the absorption especially in some subjects since no drug was observed during the 12-h observation period in 2 and 5 of the subjects after a light and heavy breakfast, respectively. At steady state the delaying effect of food on absorption had almost disappeared. No significant differences were observed in Cmax- or AUC0-12-values between the fasting and the fed states both after a single dose or at steady state. It is concluded, that food does not affect the mean bioavailability of erythromycin acistrate neither the mean rate of absorption but in some subjects the absorption from enteric coated tablets might be significantly delayed. PMID- 1586387 TI - Pharmacokinetics of the gonadotropin-releasing hormone agonist buserelin after injection of a slow-release preparation in normal men. AB - The pharmacokinetics of the gonadotropin-releasing hormone (GnRH) agonist buserelin (D-Ser(BUt)6-GnRH-(1-9) nonapeptide-ethylamide, Hoe 766, CAS 57982-77 1) after injection of a slow-release preparation was investigated in 16 healthy young male volunteers. Eight volunteers received a buserelin implant of 3.3 mg and 8 volunteers one of 6.6 mg by subcutaneous injection. In order to prevent androgen deficiency symptoms caused by the GnRH agonist all volunteers were injected with an initial loading dose of 400 mg of the androgen 19 nortestosterone hexyloxyphenylpropionate one week prior to the buserelin administration, followed by injections of 200 mg once every three weeks up to week 23. Maximal buserelin serum levels were measured two days after injection of the implant. Following a slow decrease in serum concentrations up to week 8, serum buserelin had disappeared by week 14 in the 3.3 mg group and by week 17 in the 6.6 mg group. The areas-under-the-serum-concentration-versus-time-curves (AUCs) for the 3.3 and 6.6 mg implants were 691 +/- 60 ng x h/ml and 1050 +/- 102 ng x h/ml, respectively (p less than 0.01). The mean residence times (MRTs) of buserelin after administration of 3.3 mg and 6.6 mg buserelin implant were 4.7 +/ 0.4 and 4.1 +/- 0.3 weeks, respectively (p greater than 0.05). Urinary excretion of buserelin showed a similar pharmacokinetic profile. However, urinary buserelin was still detectable at very low concentrations by the end of the study, i.e. 29 weeks after implant injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586386 TI - Fish oil treatment and apolipoprotein(a). AB - Two recent reports showed a lowering of elevated lipoprotein(a) levels upon treatment with fish oil. The aim of this paper was to confirm this finding and to establish a dose-effect relationship. A double blind, placebo controlled cross over study was carried out in 48 subjects with apolipoprotein(a) ("Apo(a)") values between 34 and 1062 U/l (median 387 U/l). The subjects were divided into 3 groups receiving 3.5, 7.1 and 10.6 g omega-3 fatty acids/day during 28 days. Parameters measured were blood levels of eicosapentaenoic acid ("EPA"), Apo(a) and fasting blood lipids. EPA levels rose in the three dosage groups by factors 7, 9 and 14, respectively, if compared to values upon placebo. Triglycerides were significantly lowered in a dose depending manner. Apo(a), however, was not changed. This held true for different baseline Apo(a) values and different fish oil dosages. It is concluded that fish oil treatment during 4 weeks cannot lower elevated Apo(a) levels. PMID- 1586388 TI - Recommendations for minimizing the risk of infection by agents causing zoonoses and other animal infections in manufacture of medicinal products. The Federal Minister for Health. PMID- 1586389 TI - Antihypertensive effect of the new calcium antagonist (+-)-3-(benzylmethylamino) 2,2-dimethylpropyl-methyl-4-(2-fluoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl 3,5-pyridinedicarboxylate hydrochloride in rats. AB - The antihypertensive effect of TC-81 ((+-)-3-(benzylmethylamino)-2,2 dimethylpropyl-methyl-4-(2-f luoro-5- nitrophenyl)-1,4-dihydro-2,6-dimethyl-3,5 pyridinedicarboxylate hydrochloride), a new calcium antagonist, was investigated in normotensive and hypertensive rats. By oral administration, the antihypertensive activity of TC-81 (ED20% in spontaneous hypertensive rats (SHR), DOCA-salt hypertensive rats and renal hypertensive rats were 0.37, 0.32, and 0.38 mg/kg p.o., respectively) was 7-14 times more potent in conscious hypertensive rats in comparison with nicardipine. Duration of the antihypertensive effect of TC-81 was about 2 times longer than that of nicardipine, and the response was elicited more slowly than that of nicardipine at an equipotent dose. Similar results were observed by intravenous injection, but the potency of TC-81 was only 3 times higher than that of nicardipine in anesthetized rats. Tolerance of the antihypertensive effect of TC-81 in long-term daily dosing and the rebound phenomenon after discontinuance of the treatment were not observed in hypertensive rats. TC-81, at a concentration of 10(-10)-3 x 10(-9) mol/l, inhibited the KCl-induced contraction of isolated rat vascular preparations. Moreover, TC-81 inhibited the norepinephrine-induced contraction of isolated SHR aorta preparation, but in isolated normotensive rat aorta, TC-81 inhibited the norepinephrine-induced contraction very little. From these observations, TC-81 can be characterized as having a strong, long-lasting, and slow-onset antihypertensive activity, especially by oral administration. Therefore, this new calcium antagonist may be useful for long-term antihypertensive therapy. PMID- 1586390 TI - Effect of recombinant human erythropoietin on the growth of human tumor cell lines in vitro. Micro-titertec-tetrazolium assay. AB - Cells derived from 9 human tumors were tested in vitro using 5 doses ranging from 1 to 5000 units of recombinant human erythropoietin (rhEpo) per ml to assess a proliferation response to this hormone. The following tumors were used: 2 melanomas, 1 hepatoma, 3 renal cell carcinomas, 1 adenocarcinoma of the lung, and 2 mammary carcinomas (with and without sex steroid hormone receptors). Compared to untreated cells, none of the cell lines exposed to rhEpo revealed differences in proliferation extending beyond the limits of methodological fluctuation. rhEpo thus does not have any effect on the growth of human tumors in vitro under the experimental conditions applied. PMID- 1586391 TI - Identification of neuronal connections by means of electron microscopic immunocytochemistry. AB - For many years neuroanatomical research has focused on the tracing of connections between populations of neurons in the central nervous system. With the development of immunocytochemical procedures employing antibodies against transmitters, transmitter-synthesizing enzymes and various neuropeptides, it has become possible to study the chemical characteristics of nerve cells. By combining tracer techniques and immunocytochemical approaches the transmitter identity of a projection can be determined. Moreover, electron microscopic double labeling procedures allow the identification of the target cells of immunocytochemically characterized presynaptic terminals. This way, by the immunocytochemical identification of transmitters or neuropeptides in defined projection neurons, a more functional interpretation of neuroanatomical data has become possible. In the present report, these combinations of techniques are demonstrated by describing recent studies of cholinergic septohippocampal projection neurons. PMID- 1586392 TI - Synaptic physiology of excitatory amino acids. AB - This paper gives a short overview of the localization of the main excitatory amino acid pathways in the mammalian brain and lists a few of the most important agonists and antagonists of the 5 excitatory acid receptors described to-date: the N-methyl-D-aspartate-(NMDA), a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-(AMPA), kainic acid-, metabotropic- and presynaptic receptors. The main part summarizes work of this laboratory on excitatory amino acids involved in the synaptic physiology of the cortico-caudate, thalamo-cortical and a local cortical pathway studied in the cat brain in vivo. It concludes by presenting two hypotheses which describe how AMPA- and NMDA-receptors could interact in the brain to modulate synaptic function, the AMPA receptors being responsible for fast synaptic transmission while activation of NMDA-receptors enhance their gain either within a single synapse or from independent synapses or extrasynaptic sites. PMID- 1586393 TI - Localization and function of the D3 dopamine receptor. AB - A novel dopamine receptor has been recently cloned, which differs from D1 and D2 receptors by its sequence, localization, pharmacology and possibly signalling system, hence its designation as D3 receptor. The D3 receptor cDNA was obtained by a combination of screenings of DNA libraries and PCR polymerase chain reaction experiments. It encodes a protein with a predicted structure consisting in 7 transmembrane domains indicating that it belongs to the G-protein coupled receptor family. Its global homology is 52% with the D2 receptor but 78% if only transmembrane domains are considered. Two shorter transcript variants, in addition to the full-length cDNA were detected by PCR in various rat brain regions. The shorter transcripts are generated by alternative splicing and encode two putative proteins respectively interrupted after the second transmembrane domain and lacking the second extracytoplasmic loop. After transfection of this latter isoform into cultured cells, no dopaminergic activity could be detected. These shorter splice variants may regulate the number of active D3 receptors. The human D3 receptor was also cloned using similar approaches with rat D3 receptor cDNA probes and was found highly homologous to the rat receptor, except in the third intracytoplasmic loop. The human D3 receptor gene was assigned to the chromosome 3 at q13.3 band. Visualisation of D3 receptor mRNA in rat brain by in situ hybridization indicated a predominant expression of the message in the ventral striatum and other "limbic" areas. There is no overlap in the distributions of D2 and D3 receptor mRNAs in discrete structures, suggesting that the two transcripts are expressed by different cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586394 TI - Functions of dopamine in the extrapyramidal and limbic systems. Clues for the mechanism of drug actions. AB - Dopamine (DA) is a neurotransmitter which modulates the transfer of information along fast-conducting pathways at the level of two main nodal points: the ventral striatum, composed by limbic areas (nucleus accumbens, tuberculum olfactorium) and the dorsal striatum, composed by extrapyramidal nuclei (caudate-putamen). These two subdivisions of the enlarged basal ganglia, are provided with different functions; accordingly, limbic DA plays an active role in goal-oriented (motivated) behaviour; instead, extrapyramidal DA is essential for execution of learned motor programs and its impairment results in the symptoms of Parkinson's disease. Various centrally acting drugs are able to interfere with DA transmission or with other neurotransmitter systems which interact with DA. Drugs of abuse owe their incentive properties to a preferential stimulation of DA transmission at the level of the limbic dopaminergic areas. On the other hand, drugs able to block glutamatergic transmission on NMDA receptors are able to selectively potentiate the action of DA at the level of a specific type of DA receptors, the D-1 type. Knowledge of the role of DA in the brain can provide the basis not only for understanding the mechanism of drug action but also for developing new strategies for the treatment of drug abuse and extrapyramidal disorders. PMID- 1586395 TI - Serotonin and psychiatric disorders. A key to new therapeutic approaches. AB - Evidence is reviewed that 5-HT (5-hydroxytryptamine, serotonin) acting through the 5-HT3 receptor subtype can influence behaviour relevant to anxiety, schizophrenia and cognitive disorders, and that 5-HT3 receptor antagonists such as ondansetron (CAS 116002-70-1) can correct behavioural disturbance in the absence of effect on normal behaviour. The 5-HT3 receptor antagonists exert a breadth of action over a wide dose range in rodent and primate models to inhibit aversive behaviour in animal models of anxiety and certain symptoms of withdrawal from drugs of abuse, alcohol, nicotine, diazepam and cocaine, to antagonise increased locomotor activity caused by mesolimbic dopamine excess, and facilitate performance in cognitive tests. The studies reveal an important role for 5-HT3 receptors in the regulation of limbic-cortical functioning, and a critical role for 5-HT3 receptor antagonists to establish the role of 5-HT3 receptors in schizophrenia, anxiety, drug withdrawal phenomena and cognitive disturbance. Preliminary clinical trials indicate a positive effect of ondansetron in anxiety, schizophrenia, alcohol withdrawal and age associated memory impairment. PMID- 1586396 TI - [Opiate addiction. Pharmacologic and biochemical aspects]. AB - The detailed information now available regarding the neurobiology of opiates (opioids) has contributed greatly to our understanding of opioid addiction. This in turn has permitted a more complete understanding of the processes underlying drug addiction. Opioid agonists with a high affinity for mu- or delta-receptors produce conditioned preferences for an environment previously associated with their administration, whereas kappa-agonists induce place aversions. Studies in which opioids were microinjected into discrete brain areas suggest that these opposing motivational effects are mediated via an interaction with the mesolimbic dopamine (DA) system originating in the midbrain. Microdialysis studies have clearly shown that mu-agonists preferentially increase DA release and metabolism in the Nucleus accumbens, whereas kappa-receptor agonists decrease release. Opposite effects on DA are observed in response to microinjections of selective antagonists for these receptor types, suggesting the existence of tonically active endogenous opioid systems which maintain DA release in the mesolimbic system: a continuous "reward" tone, probably mediated by beta-endorphin in the ventral tegmentum of the midbrain and an "aversive" tone, mediated by dynorphin in the Nucleus accumbens. Aspects of such a bidirectional regulation of the mesolimbic system by endogenous opioids are discussed. PMID- 1586397 TI - Dopaminergic and serotonergic effects of clozapine. Implications for a unique clinical profile. AB - The clinical profile of clozapine (CAS 5786-21-0) is characterized by superior efficacy in reducing the positive and negative symptoms of schizophrenia and a greatly reduced propensity to elicit acute extrapyramidal symptoms (e.g., Parkinsonian symptoms), long-term effects (e.g., tardive dyskinesia) and hyperprolactinemia. For these reasons clozapine is considered the prototypic atypical antipsychotic. The failure of clozapine to elevate serum prolactin concentrations may be related to the stimulatory effect of clozapine on tuberoinfundibular dopamine neurons and/or the failure of clozapine to achieve effective blockade of pituitary dopamine D2 receptors. The lack of acute blockade of striatal D2 receptors by clozapine and the failure of chronic clozapine treatment to suppress striatal dopamine release, relative to that produced by typical antipsychotic agents, may account for the lack of acute extrapyramidal symptoms and tardive dyskinesia, respectively, associated with the use of clozapine. Although the neurochemical substrates that subserve the unique preclinical and clinical profile of clozapine have not been determined unequivocally, clozapine and other purported atypical antipsychotic agents produce a greater antagonism of 5-HT2 receptors relative to D2 receptors than is the case for typical antipsychotics. Clozapine also exerts antagonism of D1 receptors. It is proposed that the selective interaction of clozapine among D2, D1, D4 and 5-HT2 receptors results in a distinctive alteration in the function of pre- and post-synaptic dopamine elements. PMID- 1586398 TI - The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. AB - OBJECTIVE: To test the short-term feasibility and efficacy of seven nonpharmacologic interventions in persons with high normal diastolic blood pressure. DESIGN: Randomized control multicenter trials. SETTING: Volunteers recruited from the community, treated and followed up at special clinics. PARTICIPANTS: Of 16,821 screenees, 2182 men and women, aged 30 through 54 years, with diastolic blood pressure from 80 through 89 mm Hg were selected. Of these, 50 did not return for follow-up blood pressure measurements. INTERVENTIONS: Three life-style change groups (weight reduction, sodium reduction, and stress management) were each compared with unmasked nonintervention controls over 18 months. Four nutritional supplement groups (calcium, magnesium, potassium, and fish oil) were each compared singly, in double-blind fashion, with placebo controls over 6 months. MAIN OUTCOME MEASURES: Primary: change in diastolic blood pressure from baseline to final follow-up, measured by blinded observers. Secondary: changes in systolic blood pressure and intervention compliance measures. RESULTS: Weight reduction intervention produced weight loss of 3.9 kg (P less than .01), diastolic blood pressure change of -2.3 mm Hg (P less than .01), and systolic blood pressure change of -2.9 mm Hg (P less than .01). Sodium reduction interventions lowered urinary sodium excretion by 44 mmol/24 h (P less than .01), diastolic blood pressure by 0.9 mm Hg (P less than .05), and systolic blood pressure by 1.7 mm Hg (P less than .01). Despite good compliance, neither stress management nor nutritional supplements reduced diastolic blood pressure or systolic blood pressure significantly (P greater than .05). CONCLUSIONS: Weight reduction is the most effective of the strategies tested for reducing blood pressure in normotensive persons. Sodium reduction is also effective. The long term effects of weight reduction and sodium reduction, alone and in combination, require further evaluation. PMID- 1586399 TI - Evolution of ecological differences in the Old World leaf warblers. AB - Sympatric species that belong to the same ecological guild usually differ in their behaviour and morphology, and these differences are often interpreted as adaptations to having to make use of different resources. Evidence supporting this interpretation comes from association between ecology and morphology among species, in which an a priori functional relationship is reasonable. But one problem with such comparisons is that members of a guild may be closely related, so the more closely related species can share a greater similarity in their morphology and ecology simply as a result of the lingering legacy of a common ancestor. In principle, the importance of historical legacy can be evaluated from phylogenetic relationships and times since divergence for all species, but this is rarely possible because these data are not available. Here we use a phylogeny for eight sympatric species of warbler in the genus Phylloscopus, based on their mitochondrial DNA sequences, to remove the effects of historical legacy. Without these effects, we find strong support for adaptive interpretations of among species variation in habitat selection, prey-size choice and feeding method. Ecological variation along any of these three niche axes is associated with predictable morphological variation. We also find evidence for historical legacy in that more closely related species are often more similar behaviourally and morphologically. This paradoxical result can be reconciled because the most closely related species tend to differ along only one niche axis, habitat choice. In contrast, the evolution of prey-size choice and feeding method occurred rapidly and early in the diversification of this group. Once a new ecological zone was occupied, subsequent morphological change along these niche axes was limited, accounting for the similarity of closely related species. PMID- 1586400 TI - Cervical spine injuries in blunt trauma patients requiring emergent endotracheal intubation. AB - Airway management in the blunt trauma patient is complicated by the potential for causing or exacerbating an injury to the cervical cord if an unstable cervical fracture is present. The records of 987 blunt trauma patients who required emergent endotracheal intubation over a 5-year period were retrospectively reviewed to determine the incidence and type of cervical spine injury and the incidence of injury based on airway management. Sixty of the patients (6.1%) had a cervical fracture; 53 were potentially unstable injuries by radiographic criteria. Twenty patients had neurologic deficits prior to intubation. Twenty-six patients with unstable injuries were intubated orally, 25 nasally, and two by cricothyrotomy. One patient developed a neurologic deficit after nasotracheal intubation. Because of a possible selection bias in which severely injured patients were preferentially referred to this trauma center, the true incidence of cervical spine injuries may be lower than the 6.1% we found. The authors conclude that the incidence of serious cervical spine injury in a very severely injured population of blunt trauma patients is relatively low, and that commonly used methods of precautionary airway management rarely lead to neurologic deterioration. PMID- 1586401 TI - Evaluating acute hand injuries in the emergency department: a comparison of physicians with varying postgraduate training backgrounds. St Louis Emergency Physicians' Association Research Group. AB - This study compared the quality of the history, physical examination, and treatment of patients with hand injuries performed by emergency physicians with varied training backgrounds. Four hundred ninety-seven patients with isolated hand injuries were evaluated by 97 physicians, who were classified into four groups: (1) emergency medicine board certified, (2) primary care specialty board certified, (3) non-board certified, and (4) moonlighting residents. The history and physical examination were separated into several variables to define deficiencies. Adequacy of treatment were determined by two emergency physicians and an orthopedic surgeon. Significant differences were found in five categories. Group no. 4 documented the history and followed the Centers for Disease Control tetanus prophylaxis guidelines better than did groups no. 1 or 2. Group no. 1 obtained x-rays less often than any other group and had a better treatment score, but the latter did not reach statistical significance. Physicians of lesser training are more meticulous about documenting a history and following treatment protocols than are residency-trained or boarded emergency physicians, but order more tests and are less likely to document adequate treatment. PMID- 1586402 TI - Acute fluoxetine overdose: a report of 234 cases. AB - Limited toxicity information is available in the medical literature on the antidepressant fluoxetine (Prozac, Dista Products Co, Indianapolis, IN). The goal of this prospective multicenter study was to develop a toxicity profile of initial signs and symptoms observed in an acute fluoxetine overdose. A prospective study was made of patients reported to one of four American Association of Poison Control Centers' regional poison control centers after ingesting an acute overdose of fluoxetine. A standard data collection form was used on all patients ingesting fluoxetine. Information obtained included age, current medications, dose, coingested drugs, presenting symptoms, vital signs, electrocardiogram abnormalities, outcome, and fluoxetine levels. The authors collected 272 cases; 234 cases met the criteria of the study. Fluoxetine was ingested alone in 87 cases and with ethanol or other drugs in the remaining 147 cases. Of the 87 cases where fluoxetine was ingested alone, 67 patients were adults and 20 were children. Symptoms that were seen in the adult group included: tachycardia (15/67), drowsiness (14/67), tremor (five/67), vomiting (four/67), or nausea (four/67). Thirty patients did not develop symptoms. Twelve of the adult overdose patients had total fluoxetine levels ranging from 232 to 1390 ng/mL. The authors conclude that symptoms that develop after an acute overdose of fluoxetine appear minor and of short duration. Aggressive supportive care is the only intervention necessary. PMID- 1586403 TI - Toxicology training in US and Canadian medical schools. AB - The objective was to determine the extent of toxicology training in US and Canadian Medical Schools. The authors took a phone survey of the medical schools in the United States and Canada. Questions asked included whether school had a required toxicology course, in what context toxicology was taught, whether basic poison management was taught, and whether a doctoral toxicologist was on staff. Quantitation of hours of toxicology instruction and toxicology-related questions was also sought. Of the 142 medical schools in the United States and Canada, 123 schools were contacted (85.4%); 107 of these schools were US schools while 16 were Canadian medical schools. One hundred two schools (82.8%) stated that toxicology was taught in pharmacology or pathology courses, while only six schools (4.9%) had separate formal toxicology courses. An average of 5.04 hours (+/- 4.6 hours) of toxicology was taught in US courses, while the Canadian average was 6.04 hours (+/- 5.2 hours). Basic poison management was taught in 75 of the schools (61%), while a toxicologist (holding either an MD or PhD degree) was on staff in 56 of the 110 schools responding to this question (51%). While no relationship existed between having a toxicologist on staff and whether poison management was taught in US schools, a significant relationship was noted in Canadian schools (P less than .05). The authors conclude that toxicology as a separate discipline (and poison management in particular) is not routinely taught in medical school. PMID- 1586404 TI - Reliability of data sources for poisoning deaths in Massachusetts. AB - The authors analyzed poisoning-related deaths in Massachusetts from 1986 and 1987 recorded in three datasets: poison center records, death certificate, and state medical examiner's office records. While 714 such deaths were found, 551 of these were prehospital deaths recorded within the medical examiner's office but not by the poison center. The poison center was not consulted in over 47% of the poisoning deaths occurring in Massachusetts hospitals. Conversely, 15% of deaths were reported to the poison center but were not found either in death certificate or medical examiner records. Concordance between all three datasets for recording the 163 poisoning-related hospital deaths was only 17%. The authors conclude that reliance on a single data source underestimates and potentially misrepresents both the numbers and types of poisoning deaths occurring in the state. They also believe the files of the medical examiner are an underappreciated, rich source of data concerning out-of-hospital deaths due to poisonings and intoxications. Their findings suggest that the regional poison center is an underused resource for the management of seriously poisoned patients. There is a need for a better working relationship between poison centers and area hospitals so that all serious intoxications and poisonings are reported to the poison center in a timely fashion. PMID- 1586405 TI - Report of nitropatch explosions complicating defibrillation. AB - Reports of complications associated with the use of electrical defibrillators have been relatively rare. In two patients, defibrillation performed over a nitroglycerin skin patch resulted in electrical arcing with a resultant flash of light and thermal injuries. Skin burns as a complication of defibrillation over nitropatches has not been previously reported. Such burn injuries respond to standard therapeutic measures. Healthcare professionals who may perform defibrillation should be aware of this potential complication. PMID- 1586406 TI - Polyglandular autoimmune syndrome: a cause of multiple and sequential endocrine emergencies. AB - The polyglandular autoimmune syndromes are a rare, inherited constellation of disorders characterized by multiple endocrine end-organ failures. Since these individuals have more than one endocrine failure, it is important to recognize these syndromes in clinical practice and be alert to the possibility of a second major endocrine organ failure after one has been diagnosed. PMID- 1586407 TI - Neurologically intact survivor of prolonged ventricular fibrillation: a case for intermediate dose epinephrine and postresuscitation infusion. AB - The authors point out that our understanding of the optimal dose of epinephrine used in the resuscitation of patients in cardiac arrest continues to evolve. Doses greater than the standard 1 mg of epinephrine every 5 minutes have been studied and shown to increase the rate of return of spontaneous circulation. However, reports of neurologically intact survivors of prolonged cardiac arrest are rare. The authors report a neurologically intact survivor of prolonged ventricular fibrillation with severe mixed acidosis who responded to intermediate doses of epinephrine and epinephrine infusion, where standard amounts had failed. Further research should be directed into the relationship between postresuscitation epinephrine infusions and neurologic outcome. PMID- 1586408 TI - The unstable occult cervical spine fracture: a review. AB - The initial evaluation and management of cervical spine injuries is of critical importance because of the impact of early treatment and management on the patient's eventual outcome. The devastation and cost of missing even one unstable cervical spine fracture is tremendous. The existence of patients with an unsuspected cervical spine fracture who have few, if any, symptoms and/or signs of an injury to the cervical spine is a valid concern and a dilemma for the practicing physician. Thus the principle of the occult unstable cervical spine fracture, which has been established as the standard of care, has major significance and implications. Recently, however, the concept of the occult cervical spine fracture has been challenged. Does the entity of an occult cervical spine fracture exist? If so, how should this affect our indications for obtaining cervical spine radiographs? The author presents the case of an unstable occult cervical spine fracture and a review of the literature. PMID- 1586409 TI - Hypokalemic paralyses: a review of the etiologies, pathophysiology, presentation, and therapy. AB - Acute hypokalemic paralysis is an uncommon cause of acute weakness. Morbidity and mortality associated with unrecognized disease include respiratory failure and death. Hence, it is imperative for physicians to be knowledgeable about the causes of hypokalemic paralysis, and consider them diagnostically. The hypokalemic paralyses represent a heterogeneous group of disorders with a final common pathway presenting as acute weakness and hypokalemia. Most cases are due to familial hypokalemic paralysis; however, sporadic cases are associated with diverse underlying etiologies including thyrotoxic periodic paralysis, barium poisoning, renal tubular acidosis, primary hyperaldosteronism, licorice ingestion, and gastrointestinal potassium losses. The approach to the patient with hypokalemic paralysis includes a vigorous search for the underlying etiology and potassium replacement therapy. Further therapy depends on the etiology of the hypokalemia. Disposition depends on severity of symptoms, degree of hypokalemia, and chronicity of disease. PMID- 1586410 TI - Are postreduction anteroposterior and scapular Y views useful in anterior shoulder dislocations? PMID- 1586411 TI - Emergency percutaneous dilatational cricothyroidostomy: use of modified nasal speculum. AB - The authors devised a percutaneous dilatational method which they believe trained physicians and nonphysicians (emergency medical technicians and paramedics) can use with safety and speed. With one blade of a modified nasal speculum embedded in a tapered small pigtail-dilator catheter, the closed, flattened instrument is forced through the cricothyroid ligament, with a twisting motion, and then opened. Only the skin is incised 1 cm in length. Then a free flow of air via attached syringe is sought before any further penetration. This guarantees accurate and safe entry into the airway. The operator forces the J-tipped dilator and speculum inward as the needle is withdrawn. At the proper depth the speculum is opened transversely, and a cuffed tracheostomy tube with an internal diameter of 6 mm is inserted. The instrument is removed and immediate suctioning and active ventilation is possible. The authors developed the use of this instrument in trials on a mannequin and on 25 cadavers. PMID- 1586412 TI - Mouth-to-mouth ventilation: the dying art. PMID- 1586413 TI - Altering the medical record. PMID- 1586414 TI - Is the anteroposterior cervical spine radiograph necessary in initial trauma screenings? PMID- 1586416 TI - Problems with prehospital cardiac resuscitation: the two-rescuer response. PMID- 1586415 TI - Is intravenous thiamine safe? PMID- 1586417 TI - Survey and comparison of the informational brochures and application forms for US emergency medicine residency programs. PMID- 1586418 TI - Toxicology education in emergency medicine residency programs. PMID- 1586419 TI - Fatal hyperkalemia from a salt substitute. PMID- 1586420 TI - The effect of toxicologic screening on management of minimally symptomatic overdoses. PMID- 1586421 TI - Rare malposition of a central venous line. PMID- 1586422 TI - Hyoid bone fracture secondary to gunshot. PMID- 1586423 TI - Orthostatic vital signs: variation with age, specificity, and sensitivity in detecting a 450-mL blood loss. AB - The authors conducted this study to: (1) determine the effect of age on orthostatic vital signs; and (2) to define the sensitivity and specificity of alternative definitions of "abnormal" orthostatic vital signs in blood donors sustaining an acute 450-mL blood loss. The population studied were 100 healthy adult volunteer blood donors and 100 self-sufficient ambulatory citizens attending a senior citizens daytime activity center. Subjects with a history of orthostatic hypotension were excluded. Subjects were first placed in the recumbent position and their rate pulse and blood pressure were determined after 1 minute; these same parameters were measured in the same arm beginning 30 seconds after standing. In blood donors measurement of orthostatic vital signs was repeated immediately after blood donation. Blood donors served as their own controls in the determination of sensitivities and specificities. Mean orthostatic vital sign changes were as follows: pulse rate, 2 +/- 7 beats per minute; systolic blood pressure, -3 +/- 9 mm Hg; and diastolic blood pressure, 1 +/- 7 mm Hg. There was no clinically meaningful variance in orthostatic blood pressure changes with age. For a given specificity, pulse rate increase was the most sensitive of the orthostatic vital signs used alone; a pulse rise of greater than 20 beats per minute had a sensitivity of 9% with a specificity of 98%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586424 TI - Flumazenil in mixed benzodiazepine/tricyclic antidepressant overdose: a placebo controlled study in the dog. AB - This study evaluates the cardiac and neurologic risks associated with the antagonization of the benzodiazepine component of mixed drug overdoses, when cyclic antidepressants are also implicated. Twenty-four mongrel dogs were anesthetized and ventilated. Electroencephalogram, electrocardiogram, and tidal carbon dioxide and arterial pressure were continuously recorded. Amitriptyline (1 mg/kg/min) associated with midazolam (1 mg/kg + 1 mg/kg/h) was infused in 12 of the dogs. Midazolam was replaced by saline in the other 12. Drug administration was continued until signs of cardiotoxicity (QRS prolongation greater than 120 milliseconds or sustained arrhythmias) occurred. At that moment, midazolam effects were suddenly reversed by administration of flumazenil 0.2 mg/kg in six dogs out of each group. Placebo was administered in the others. Reactions were observed for the next 120 minutes. Midazolam-induced sedation efficiently protects (P less than .02) against seizures due to amitriptyline toxicity. This protective effect is counteracted by flumazenil. Midazolam has limited influence on the cardiac toxic effects of amitriptyline. The bolus of flumazenil is, however, associated with a significant worsening of electrocardiogram disturbances, and two sudden deaths were recorded. The mechanism of this effect remains unclear, as it could be unrelated to the antagonization of midazolam sedation. Given the problem of extrapolating animal data to humans, these results suggest that bolus administration of high doses of flumazenil in mixed intoxication implicating benzodiazepine and cyclic antidepressants has the potential to precipitate convulsions and/or arrhythmias. A slowly titrated administration of the antidote, as usually recommended, could prevent these effects. PMID- 1586425 TI - Initial symptoms as predictors of esophageal injury in alkaline corrosive ingestions. AB - The predictive value of initial clinical evaluation in the management of alkaline corrosive ingestion remains unclear. This multicenter study was designed to determine if specific clinical signs and symptoms following ingestion of alkaline corrosives could predict significant esophageal injury. Alkaline corrosives were defined by a pH greater than or equal to 12. Signs and symptoms previously suggested as predictive of significant esophageal injury were documented on a standardized data form. Esophagoscopy reports were reviewed blinded to initial symptoms. Three hundred thirty-six alkaline-corrosive ingestions were analyzed. The mean number of symptoms reported in patients who did not have esophagoscopy was 1.2, in patients who had esophagoscopy was 3.0, and in patients that had visualized second or third degree esophageal burns was 4.8. Of 88 patients who had esophagoscopy, 63 (72%) had both the esophagoscopy report and initial symptom assessment available. Esophagoscopy was positive, defined as second or third degree esophageal burns, in 18 of 63 cases (29%). All patients with significant burns were symptomatic. No single or group of initially reported signs and symptoms could identify all patients with potentially serious esophageal burns. PMID- 1586426 TI - Triage of patients out of the emergency department: three-year experience. AB - Because of severe emergency department (ED) overcrowding, the authors initiated a program of referring certain patients who were assessed as not needing emergency care away from the ED. A selected group of patients who presented to a busy university ED were refused treatment and triaged away following a medical screening examination performed by a nurse. In this 3-year study 136,794 patients presented to the triage area in the ED, of which 21,069 (15%) were refused care and referred elsewhere. Letters and calls to all referral clinics, eight local EDs, and the coroner's office identified no patients who had been grossly mistriaged, and only insignificant adverse outcomes could be identified. Additional follow-up on 3,740 individuals triaged away was performed by telephone. Responses from this survey indicated that 42% of persons received care elsewhere the same day, 37% within 2 days, and 22% decided not to seek medical care. A group of 1.6% sought care at other hospital EDs for minor complaints. The authors concluded that a group of patients can be selectively triaged out of the ED without significant adverse outcomes, which may offer one approach to the problem of ED overcrowding. PMID- 1586427 TI - Serum determinations in toxic isopropanol ingestion. AB - A toxic dose of isopropyl alcohol was ingested by six male mongrel dogs to evaluate the relationship between acetone production and isopropyl degradation. Maximal serum isopropyl levels were achieved approximately 2 to 3 hours after ingestion of 60 mL of 70% isopropyl alcohol. Acetonemia occurred rapidly in the serum (within 15 minutes of ingestion) and continued to rise after isopropanol levels plateaued. The levels of acetone and isopropanol correlated positively throughout the study model with an r of .54 (P less than .001). It is concluded that there is a positive relationship between acetone production and isopropyl metabolism in the setting of a toxic ingestion of isopropanol. Acetone's persistence as a serum marker may be beneficial in identifying isopropyl hours after a suspected ingestion. PMID- 1586428 TI - Prevalence of folate deficiency in emergency department patients with alcohol related illness or injury. AB - To assess the prevalence of folate deficiency in emergency department patients with alcohol-related illness or injury, a prospective, nonconsecutive case series with nonrandomized controls was used. All patients presenting to a 60,000-visit public hospital emergency department with alcohol-related illness or injury were eligible; patients were excluded if they had received folate in our health care facility within the previous 4 months. An alcohol and brief dietary history was obtained, and a complete blood cell count and red blood cell folate level was performed on each patient. Analysis was undertaken by chi 2 to evaluate the prevalence of folate deficiency in the alcohol-related versus the control population. One hundred three patients were entered into the study. Three patients were subsequently excluded from analysis. Of 52 study patients, three (5.8%) were found to be folate deficient. Of 48 controls, two (4.2%) were found to be folate deficient. This difference is not statistically significant (P greater than .05, chi 2; mean difference 1.6%, 95% confidence interval -6.9% to 10.1%). The prevalence of folate deficiency in patients presenting to this emergency department with alcohol-related illness or injury is low, and does not differ from the general emergency department population. Empiric folate therapy in these patients is not indicated. PMID- 1586429 TI - Physicochemical characteristics of drugs and response to repeat-dose activated charcoal. AB - Although the administration of repeated doses of activated charcoal has been advocated to increase the systemic clearance of many drugs, it is unknown whether a drug's physicochemical properties are associated with enhanced removal by repeat-dose activated charcoal. The English language literature was searched to identify clinical studies evaluating repeat-dose activated charcoal. Percent reduction in plasma elimination half-life during repeat-dose activated charcoal was calculated and correlated with the drugs' characteristics. A step-wise multiple regression analysis with the independent variables of the drugs' molecular weight, pKa, plasma protein-binding, intrinsic plasma elimination half life, and volume of distribution failed to identify potential predictors (P = .1) of effectiveness of repeat-dose activated charcoal. This analysis suggested that charcoal therapy was more effective for drugs with a longer intrinsic half-life (r2 = .24, P = .04). A uniform framework that evaluates the physicochemical characteristics of drugs and their response to repeat-dose activated charcoal is needed to better define which patients would benefit from repeat-dose activated charcoal therapy. PMID- 1586430 TI - Potentiation of cocaine and d-amphetamine toxicity with caffeine. AB - The effect of caffeine when combined with cocaine or amphetamine was studied in rats. Animals were pretreated with intraperitoneal vehicle (normal saline [NS]) or caffeine 100 mg/kg, then challenged with intraperitoneal cocaine (0, 35, 50, 70, or 90 mg/kg) or intraperitoneal d-amphetamine (0, 15, 25, 35, or 42 mg/kg). Animal behavior, time to, and incidences of seizures and death were recorded. This dose of caffeine alone did not cause seizures or death. Caffeine pretreatment significantly increased the incidence of overt seizures induced by either cocaine or amphetamine. Caffeine increased the incidence of cocaine induced death from 10% to 90% at the 70 mg/kg cocaine dose (P less than .01). Caffeine increased amphetamine-induced death from 0% to 80% at 15 mg/kg (P less than or equal to .01), 10% to 70% at 25 mg/kg (P less than or equal to .01), and 30% to 80% at 35 mg/kg (P less than or equal to .01). To investigate mechanisms, additional animals were pretreated with the adenosine agonist, 2-chloroadenosine (2.5 and 10 mg/kg), before being challenged with NS, 90 mg/kg cocaine, or 42 mg/kg amphetamine. Pretreatment with 2-chloroadenosine had no affect in reducing cocaine or amphetamine toxicity. Combination pretreatment with caffeine and 2 chloroadenosine potentiated cocaine toxicity. The phosphodiesterase inhibitor, pentoxifylline, did not potentiate cocaine toxicity. The authors conclude that caffeine potentiates the acute toxicity of both cocaine and amphetamine, and that the failure of 2-chloroadenosine to alter this suggests that the toxicity of the stimulants cocaine and amphetamine may be modulated by nonspecific rather than specific adenosine- or phosphodiesterase-induced mechanisms. PMID- 1586431 TI - The John Doe syndrome: diagnosis and outcome of patients unidentified at the time of emergency department admission. AB - Patients unidentified at the time of admission to urban emergency departments are a group about whom little is known. To determine the medical diagnoses and outcomes of these "John" and "Mary Does", we reviewed emergency department charts for these patients admitted from January 1 to December 31, 1988. During this period there were 344 initially unidentifiable patients, for 0.44% of all visits. Age was 36.9 +/- 15.6 years (mean +/- SD); 71% were male. All patients had one or more of the following diagnoses, with mortality highest for cardiopulmonary arrest (n = 42, mortality = 100%), followed by major trauma (163, 68%), drug overdose (27, 41%), miscellaneous medical conditions (11, 18%), neuropsychiatric disorders (59, 12%), acute alcohol intoxication (62, 0%), and seizures (13, 0%). Overall mortality was 47%. Identification was made prior to hospital discharge in 92% of cases. In this group, the most common sources of information were the patient (38%), family (19%), or documents eventually found on the person or in belongings (4%). Survivors were much more likely to be identified than those who died (99% versus 84%, P less than .0001). These observations describe a John Doe syndrome in patients whose identity is obscured by critical illness, the effects of drugs or alcohol, or neuropsychiatric disease. Economic privation is a major underlying risk factor. PMID- 1586432 TI - Myocardial infarction associated with inappropriate use of topical cocaine as treatment for epistaxis. AB - A case of a 57-year-old man with hypertension and stable angina, on aspirin therapy, who was treated for epistaxis with intranasal cocaine, and who subsequently suffered a non-Q wave myocardial infarction is reported. Of note, the cocaine was administered in a manner which differs from that advocated in standard references. Specifically, intranasal packing soaked with 4% cocaine was left in place with continuous nasal mucous membrane contact over 5 to 6 hours. The authors speculate that myocardial infarction occurred on the basis of coronary artery spasm. This case should alert practitioners to myocardial ischemia occurring as a complication of the therapeutic use of intranasal cocaine for the treatment of epistaxis. PMID- 1586433 TI - Esophagotracheal perforation during an emergency intubation. AB - The authors report the first known case of a simultaneous esophagotracheal perforation, which occurred during an emergency intubation of a patient with airway abnormalities. The perforation was suspected from the postintubation chest roentgenograph and confirmed by fiber optic bronchoscopy which showed that the endotracheal tube had entered through the posterior wall of the trachea after perforating the esophagus. The patient had a tracheostomy done and was placed on prophylactic antibiotic therapy; the esophageal tear was left to heal spontaneously. Risk factors for esophagotracheal perforation, means to avoid it, and diagnosis and treatment considerations are discussed. PMID- 1586434 TI - Scanned computed tomography image transmission by modem: feasibility for emergency department transfers. PMID- 1586435 TI - Venomous snakes of southwest Asia. AB - This report provides a brief description of the venomous snakes encountered in Southwest Asia, as well as a brief review of the clinical implications of envenomation from each animal. Specific therapy for snake envenomation in the United States is somewhat controversial, and it is no less controversial with animals from this region. The most logical approach probably combines medical management with antivenom when available, and surgical intervention when clearly indicated due to elevated compartment pressure or massive tissue necrosis. Antivenom is available for all species except W aegyptia (in vitro only) and Atractaspis species. Antivenom for V palaestinae may be used for Atractaspis envenomation (Tables 2 and 3). PMID- 1586436 TI - Traumatic abdominal hernia: report of three cases and review of the literature. PMID- 1586437 TI - Emergency radiology of urinary tract injuries. PMID- 1586438 TI - Cases in electrocardiography. PMID- 1586439 TI - Emergencies of indwelling venous catheters. PMID- 1586440 TI - Assessing values: rationing emergency department care. PMID- 1586441 TI - Estimating laceration length: a cost containment issue. PMID- 1586442 TI - Kerr Insta-Char activated charcoal product. PMID- 1586443 TI - Misinterpretation of normal radiographic anatomy for mandibular fractures. PMID- 1586444 TI - The delayed-action stab, resulting in an incarcerated diaphragmatic hernia. PMID- 1586445 TI - Avoiding needle-stick injuries in the emergency department. PMID- 1586446 TI - Dexamethasone-induced perineal irritation in head injury. PMID- 1586447 TI - Multiple BCR-related gene products and their proposed involvement in ligand induced signal transduction pathways. PMID- 1586448 TI - Association of induction of a fully tumorigenic phenotype in murine radiation induced T-lymphoma cells with loss of differentiation antigens, gain of CD44, and alterations in p53 protein levels. AB - We investigated the mechanism of radiation induction of murine thymic lymphomas by studying the characteristics of primary x-ray-induced thymic lymphoma (PXTL) cell lines and of their oncogene-induced, progressed progeny. It is widely thought that proto-oncogene alterations are associated with the induction of murine lymphomas; however, few, if any primary murine radiation-induced lymphomas possess (proto-)oncogene alterations. Independently derived cell lines grown directly (i.e., without in vivo transplantation) from thymic lymphomas of irradiated C57BL/6 mice possess the properties of immortalized pre-T cells and lack many of the characteristics of "tumor cells". PXTL cells are poorly tumorigenic upon transplantation, do not clone in methylcellulose cultures, are growth factor dependent and autocrine, and lack consistent chromosome and oncogene abnormalities. However, the thymic lymphomas are malignant and cause the death of each afflicted mouse. PXTL cells expressed two immunologically distinct forms of the tumor suppressor protein p53 that have moderately increased stability (t1/2 = 1 h) when compared with p53 of normal splenic T lymphocytes. Early PXTL cells could progress in vitro to a fully tumorigenic phenotype after infection with retroviruses encoding the c-myc and v-ras oncogenes. Progressed T lymphoma cells acquired growth factor independence, a highly transplantable and tumorigenic phenotype, and the ability to quantitatively clone in methylcellulose cultures. Progressed lymphoma cells coordinately downregulated the expression of five T-cell differentiation markers, upregulated the expression of CD44 (Pgp-1), and harbored vastly elevated levels of two immunologically distinct forms of p53. Our results suggest that the early thymic lymphomas consist of differentiation inhibited, immortal pre-T cells that are precursors to progressed, fully tumorigenic T-lymphoma cells. PMID- 1586449 TI - Elevated expression of the ribosomal protein S2 gene in human tumors. AB - Differential screening of a cDNA library was used to isolate genes differentially expressed in a nontumorigenic clone and a ras-transformed variant of the human teratocarcinoma cell line PA-1. The RNA transcript for one of the cDNA clones that we identified was expressed at a 25-fold higher level in the ras-transformed PA-1 cells than in the nontumorigenic PA-1 cells. DNA sequence analysis of this clone showed that it had 86% nucleic acid homology to the mouse LLRep3 gene and only differed at a single amino acid codon (codon 198), which is changed from serine in LLRep3 to threonine in this cDNA clone. The rat ribosomal S2 protein is closely related to the yeast omnipotent informational suppressor SUP44, which encodes the yeast ribosomal protein S4; to the mouse protein LLRep3; and to the human cDNA clone we describe in this report. We therefore concluded that this clone codes for the human ribosomal S2 protein. In situ hybridization experiments revealed that expression of this gene was elevated in cultured human head and neck squamous cell carcinomas compared with normal keratinocytes. In situ hybridization experiments also demonstrated that expression of this gene was elevated in histological sections of human premalignant leukoplakia, head and neck squamous cell carcinomas, and colon and breast cancers compared with the adjacent normal tissues. S2 expression may be a useful diagnostic or prognostic marker for grading human tumors. PMID- 1586450 TI - Increased expression of cathepsins L and B and decreased activity of their inhibitors in metastatic, ras-transformed NIH 3T3 cells. AB - We previously found that the T24 Ha-ras oncogene induces metastatic ability in NIH 3T3 cells and that this change depends on expression of the ras oncogene. As part of our studies on mechanisms by which ras may induce metastasis, we investigated expression and activity of two cysteine proteinases, cathepsin L (major excreted protein) and cathepsin B, as well as cysteine proteinase inhibitor activity, in ras-transformed NIH 3T3 cells. In a series of cel lines that expressed differing amounts of ras, we found a good correlation between levels of ras expression and cathepsin L expression (r = 0.80). There was also a good correlation between secreted procathepsin L protein levels and experimental metastatic ability (r = 0.88). We found a similar but less strong association between cathepsin B levels and metastatic ability in these cells (r = 0.76 and r = 0.72 for 2.2-kb and 4.1-kb transcripts, respectively). Functional cathepsin L plus B activity (both secreted and cell-associated) was found to be higher in ras transformed cells and was dependent on cell confluency in culture. Coupled with increased expression and activity of cysteine proteinases, ras-transformed NIH 3T3 cells showed reduced cysteine proteinase inhibitor activity. We conclude that the balance between expression of cysteine proteinases and their inhibitors may be coregulated by ras expression. Our results suggest that ras-induced increases in production of degradative enzymes such as cathepsins L and B, along with decreased activities of their inhibitors, may contribute to the increased malignant properties of ras-transformed NIH 3T3 cells. PMID- 1586451 TI - A comparative study of the low-molecular mass serine proteinase inhibitors of human connective tissues. AB - Low molecular mass serine proteinase inhibitors isolated from human articular cartilage, intervertebral disc, meniscus, and costal cartilage were compared chromatographically. Similar charge and size properties were exhibited when these inhibitors were examined by gel permeation and cation exchange chromatography. The individual proteinase inhibitory species separated by these procedures all cross-reacted with a polyclonal antibody raised against the mucous proteinase inhibitors (MPIs) obtained from human bronchial secretions, however the distribution of these MPI-like species varied with the origin of the connective tissue. The major inhibitory species present in human articular cartilage and intervertebral disc were purified to homogeneity using gel filtration, cation exchange, trypsin affinity and high performance reverse phase chromatography. The amino-terminal sequences of the purified cartilage intervertebral disc inhibitors was found to be identical to the published sequence of MPIs isolated from parotid and seminal secretions. These findings indicate that the endogenous small molecular mass cationic serine proteinase inhibitory proteins present in human cartilaginous connective tissues are members of the MPI family of proteinase inhibitors. PMID- 1586452 TI - The tungsten-containing aldehyde oxidoreductase from Clostridium thermoaceticum and its complex with a viologen-accepting NADPH oxidoreductase. AB - Purification of aldehyde oxidoreductase from C. thermoaceticum, the first detected enzyme able to reduce reversibly non-activated carboxylic acids to the corresponding aldehydes (White, H., Strobl, G., Feicht, R. & Simon, H. (1989) Eur. J. Biochem. 184, 89-96), results in the generation of multiple forms of the enzyme. The specific activities for the viologen-mediated dehydrogenation of butyraldehyde for the two main forms of the purification procedure are 530 and 450 U/mg. Two forms of the enzyme composed of alpha,beta- and alpha,beta,gamma subunits, can be differentiated. The latter binds to red-Sepharose and can be eluted very specifically with NADPH. In contrast to the alpha,beta-types the trimeric forms also catalyse the reversible reduction of oxidised viologen with NADPH (VAPOR activity). The dimer alpha,beta can oligomerize and the alpha,beta,gamma-trimer can easily form various oligomers or split off the gamma subunit. The apparent molecular masses of the subunits alpha,beta and gamma are 64, 14 and 43 kDa. The alpha,beta-form reveals an apparent molecular mass of 86 kDa containing about 29 iron, 25 acid-labile sulphur, 0.8 tungsten and forms about 1 mol pterine-6-carboxylic acid by permanganate oxidation. The corresponding values of the trimer showing a mass of 300 kDa, are about 82 Fe, 54 S, 3.4 W and 2.5 pterine-6-carboxylic acid. In addition, 1.7 mol of FAD could be found which seems to be a component of the gamma-subunit. The aldehyde oxidoreductase from C. thermoaceticum and that from C. formicoaceticum (White, H., Feicht, R., Huber, C., Lottspeich, F. & Simon, H. (1991) Biol. Chem. Hoppe Seyler 372, 999-1005) show qualitative similarities as far as the Fe, S, W and pterin content and the broad substrate specificity are concerned. However, there are also surprisingly marked differences with respect to composition and amino acid sequence. PMID- 1586453 TI - Primary structures of neuropeptides isolated from the corpora cardiaca of various cetonid beetle species determined by pulsed-liquid phase sequencing and tandem fast atom bombardment mass spectrometry. AB - A peptide with the same retention time on gradient reversed-phase high performance liquid chromatography was present in the corpora cardiaca of 5 scarabaeid beetles, subfamily Cetoniinae: the three fruit beetle species Pachnoda marginata, P. sinuata and P. aemulae and the two protea beetle species Trichostetha fascularis and T. albopicta. Crude corpora cardiaca material from P. sinuata had a small hypertrehalosaemic effect in American cockroaches and a very weak hyperlipaemic activity in migratory locusts. Injections into P. sinuata caused hypertrehalosaemia when a dose of 1.0 corpora cardiaca equivalents was injected. An identical neuropeptide was isolated, by RP-HPLC, and sequenced by pulsed-liquid phase sequencing employing Edman chemistry after enzymically deblocking the N-terminal 5-oxopyrrolidine-2-carboxylic acid residue, as well as by collision-induced decomposition tandem fast atom bombardment mass spectrometry. The peptide is a blocked octapeptide: Glu-Leu-Asn-Tyr-Ser-Pro-Asp TrpNH2, previously designated Mem-CC. The synthetic peptide is able to elicit haemolymph carbohydrates in P. sinuata upon injection of low doses. Activity studies using synthetic analogues of this peptide revealed that Tyr4 may be important for receptor recognition/binding. The peptide is synthesized in intrinsic cells of the corpus cardiacum as shown by in vitro incorporation of [3H]Trp and [14C]Tyr in Mem-CC. PMID- 1586454 TI - Design and synthesis of a novel biotinylated photoreactive insulin for receptor analysis. AB - B1-(4-Azido-salicyloyl)-[B1-biocytin,B2-lysine]insulin was synthesized by double Edman degradation of A1,B29-Msc2-insulin and stepwise acylation at the N-terminus of the B-chain. This derivative is homogeneous in RP-HPLC and has a biological in vitro activity of 20% and receptor binding of 15%, relative to insulin. Radioiodination and HPLC gave the B1-labelled 125I-derivative (I) as well as the 4 isomers with 125I-labelled tyrosine (A14, A19, B16, B26). UV-induced crosslinking of I with insulin receptors led to specific labelling of the alpha subunit (Mr 130,000). The peptide bond LysB2-AspB3 is completely cleavable by trypsin (EC 3.4.21.4). I is thus a new tool for the analysis of the hormone binding region by making possible the isolation of tryptic, biotinylated receptor fragments labelled by the dipeptide 125I-4-azidosalicyloyl-biocytinyl-Lys. PMID- 1586455 TI - Accumulation of ester- and ether-linked phosphatidates by HeLa cells in response to ionophore A23187 through activation of phospholipase D. AB - Phosphatidates seem to play an important role in the control of cell proliferation modified by ligands (M. Kaszkin et al. 1991, Cancer Res. 51, 4328 4335). In this study the potency of calcium ionophore A23187 to alter phosphatidate levels in HeLa cells as a model was studied in detail. HeLa cells prelabeled with [14C]arachidonic acid responded to calcium ionophore A23187 with a rapid accumulation of labeled 1,2-diacylglycerophosphate (acyl-PA) and 2-acyl-1 O-alkylglycerophosphate (alkyl-PA) with a first peak at 5 min and a second increase starting at 20-30 min. In cells prelabeled with [14C]oleic acid the ionophore mobilized relatively more of labeled acyl-PA. The total amount of phosphatidates mobilized was in the order of 0.2 micrograms/10(6) cells, i.e. an almost 10(-4)M concentration. The transphosphatidylation of labeled acyl- and alkyl-PA to 1-butanol in all cases showed that activation of phospholipase D had occurred. The reaction became detectable at 10(-6)M ionophore and was fully expressed at 10(-5)M. Butyl phosphatidate generated during 1 h treatment with ionophore amounted to approx. 0.5 nmol per 10(6) cells (i.e. 10(-4)M conc. within cells) as shown by the use of [14C]butanol. The 3-5-fold rise of the overall phosphatidate level is probably sufficient to alter physically cellular membranes, particularly if the new phosphatidate is restricted to certain compartment(s). PMID- 1586456 TI - Cloning and overproduction of biodegradative threonine deaminase from Escherichia coli W strain. AB - We have cloned the structural gene (tdcB) of biodegradative threonine deaminase from Escherichia coli W strain by utilizing the polymerase chain reaction. The JM109/pUCTDA strain, which was obtained by transforming E. coli JM109 with a vector plasmid (pUCTDA) containing the cloned tdcB gene, produced a large amount of the enzyme corresponding to more than 5% of the total soluble protein. Amino acid sequence analysis of this recombinant enzyme showed that the amino acid sequence is identical to the nucleotide-deduced sequence of biodegradative threonine deaminase from E. coli K-12. PMID- 1586457 TI - In vitro targeting of erythrocytes to cytotoxic T-cells by coupling of Thy-1.2 monoclonal antibody. AB - A method was explored to develop a general means to target erythrocytes to T cells in vitro. Mouse erythrocytes were coupled with an anti-Thy-1.2 monoclonal antibody by two methods. Chromic chloride coupling of antibody was preferred to biotinylation. The morphology, osmotic fragility, and the hematological values of treated cells were normal compared with those of control erythrocytes. Antibody coupled erythrocytes were incubated with cytotoxic T-lymphocytes (CTLL) in vitro at a 20:1 ratio. Approximately 60-70% of the CTLL formed rosettes. The cell mixture was subjected to gradient centrifugation and separated into four fractions. THe rosettes were clearly identified only in the treated group containing anti-Thy-1.2-coupled erythrocytes. No rosettes were found when aspecific monoclonal antibody was coupled to erythrocytes. Examination by scanning and transmission electron microscopy revealed CTLL with 4-5 erythrocytes attached to them but did not show any evidence of membrane fusion. Rosettes of CTLL incubated in vitro proliferated as well as CTLL alone and maintained their dependency on interleukin-2. Targeting of erythrocyte carriers to lymphocytes offers the potential for delivery of molecules directly to the target cell. PMID- 1586458 TI - Beta-glucosidase from Penicillium purpurogenum: purification and properties. AB - beta-Glucosidase was purified from the culture supernatant of Penicillium purpurogenum. The purified enzyme was homogeneous on both nondenaturing and sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. The enzyme is a monomeric glycoprotein with M(r) of 90,000 as determined by gel filtration on Bio Gel P-300 and SDS-polyacrylamide gels. Two enzyme forms were resolved by chromatofocusing and isoelectric focusing, and the pI values obtained with both methods were 4.2 (major form) and 6.0. The major form was characterised further. Enzyme activity was optimal at pH 3.5 and at 60 degrees C. The enzyme was stable in the pH range 2.5-9.5 for 24 h at 4 degrees C. Kinetic analysis gave Kms of 0.8 mM for cellobiose and 85 microM for p-nitrophenyl-beta-D-glucopyranoside. The enzyme hydrolyses a wide range of substrates including aryl-beta-glucosides, cellobiose, and amygdalin. Glucose inhibits competitively and glucono-delta lactone is a mixed inhibitor of the enzyme. PMID- 1586459 TI - Purification and primary structure of pyruvate decarboxylase from Zymomonas mobilis. AB - Pyruvate decarboxylase (E.C. 4.1.1.1), the key enzyme in the glycolytic pathway to ethanol, was isolated in gram amounts from Zymomonas mobilis for structural studies. The primary structure was determined by automated Edman degradation and compared with that deduced from the DNA sequence of the structural gene, previously published by two groups (A. D. Neale, R. K. Scopes, R. E. H. Wettenhall, and N. J. Hoogenraad, 1987, Nucleic Acids Res. 15, 1753-1761; M. Reynen, and H. Sahm, 1988, J. Bacteriol. 170, 3310-3313). The peptide data differ from the published DNA sequences, which also deviate from each other. Crystals diffracting to about 0.3 nm resolution have been obtained by the hanging drop vapor diffusion method. The space group was identified as P4(1)22 or its enantiomorphs containing presumably one tetramer per asymmetric unit. PMID- 1586460 TI - Increased glucose metabolism by enzyme-loaded erythrocytes in vitro and in vivo normalization of hyperglycemia in diabetic mice. AB - The main metabolic properties of human red blood cells (RBC) overloaded with glucose catabolizing enzymes such as hexokinase and glucose oxidase were evaluated. Human erythrocytes loaded with human hexokinase metabolized 3.1 +/- 0.2 mumol/h/ml RBC of glucose, an amount double that consumed by normal and unloaded cells (1.46 +/- 0.16 mumol/h/ml RBC), while glucose oxidase-loaded erythrocytes consumed up to 5.5 +/- 0.5 mumol/h/ml RBC of glucose but with a time dependent increase in methemoglobin formation due to the H2O2 produced in the glucose oxidase reaction. This methemoglobin production was greatly reduced while glucose consumption was increased (8.1 +/- 0.4 mumol/h/ml RBC) by coentrapment of hexokinase and glucose oxidase. Similar results were obtained in mouse red blood cells, although the role of hexokinase was less pronounced due to a higher basal level of this enzyme. When administered to diabetic mice the hexokinase/glucose oxidase-overloaded erythrocytes had a circulating half-life of 5 days and were able to regulate blood glucose at near physiological levels. A single intraperitoneal administration of 500 microliters of enzyme-loaded cells maintained a near-normal blood glucose concentration for 7 +/- 1 days, while repeated administrations at 10-day intervals were effective in the regulation of blood glucose levels for several weeks. These results suggest that enzyme-loaded erythrocytes can behave as circulating bioreactors and can provide a new way to reduce abnormally elevated blood glucose. PMID- 1586461 TI - The antimutagenic and anticarcinogenic effects of tea, garlic and other natural foods in China: a review. PMID- 1586462 TI - In vivo and in vitro acetylcholinesterase inhibition by metacid-50 and carbaryl in Channa punctatus under natural field condition. AB - Channa punctatus (Bloch), cultivated under paddy-cum-fish culture programs, was exposed to non-lethal levels of 0.239 ppb of Metacid-50 and 3.73 ppm of Carbaryl for 7 days in the field. These insecticides effected significant inhibition of brain acetylcholinesterase (AChE) activity accompanied by a concurrent increase in acetylcholine (ACh). In vitro inhibition of brain acetylcholinesterase was also compared between unexposed and pesticide exposed fish. Data revealed that the time taken for 50% inhibition (t0.5) of the enzyme was less in the pesticide exposed fish as compared to that of the unexposed fish. This indicates a preformed effect of the test pesticides on fish brain AChE during the in vivo exposure while the in vitro effect is an additive inhibition of the enzyme caused by the circulating inhibitors reducing the t0.5. Acetylcholinesterase inhibition may thus be utilized to monitor pesticide pollution in agricultural fields. PMID- 1586463 TI - Biodegradation of aniline and abundance of potential degraders in river waters. AB - Total dissolved organic carbon (TOC), number of colony forming units (CFU), and total direct count (TDC) were compared to the biodegradation of aniline and the number of potential degraders in water samples from head waters to down stream of the Ina River and several other sites of rivers traversing Osaka city. The results indicate that aniline degrading populations of these various microbial communities exhibit different activities probably depending on the extent of adaptation to pollutants to which the microbes are exposed. The number of aniline degraders found in river water samples was in agreement with other parameters which were used to demonstrate the degree of pollution in river water even though higher biodegradability was evident in waters which show comparatively low TOC and CFU. These results suggest that biodegradation of aniline and enumeration of its potential degraders may serve as valuable indicators for the assessment of pollution in river waters. PMID- 1586464 TI - Relative toxicity of aldrin, fenvalerate, captan and diazinon to the freshwater food-fish, Clarias batrachus. AB - The median lethal concentrations (LC50S) of aldrin, fenvalerate, captan and diazinon were determined for Clarias batrachus by trimmed Spearman-Karber method. The potency ratios of toxicity among them were analysed by parallel-line bioassay with quantal responses. The LC50S for 40 day of exposure of aldrin, fenvalerate, captan and diazinon were 0.00036, 0.0094, 0.5473 and 2.4186 ppm respectively. These values were lower than those obtained for an exposure of 96 hour. It shows the greater toxicity of the pesticides in a long-term exposure. The relative toxic potency of aldrin fenvalerate, captan and diazinon was in a ratio of 6807:241:4:1 respectively. Thus the chemically different groups of pesticides exhibit an order of toxicity as aldrin greater than fenvalerate greater than captan greater than diazinon for the freshwater catfish, Clarias batrachus. It infers that the catfish is most sensitive to aldrin and least sensitive to diazinon. The comparison of the sensitivity of various species tested against these pesticidal chemicals has also been done to review the available information. PMID- 1586466 TI - Effect of cycloheximide on the adaptive response induced by low dose radiation. AB - Human lymphocytes pre-exposed to 10 mGy or 50 mGy of X-rays become less sensitive to subsequent large dose irradiation, exhibited lower rate of chromosome aberration than expected. This adaptive response could be inhibited by cycloheximide, a protein synthesis inhibitor for successive 2 h period ranging from 0.5h before to 4h after the low dose exposure, indicating that the adaptive response was directly related with the protein synthesis. PMID- 1586465 TI - Preventive effect of vitamin E in cadmium intoxication. AB - The influence of vitamin E on cadmium intoxication was investigated in rats. The exposure to cadmium (1 mg/kg, Cd as CdCl2.2H2O, intraperitoneally for 7 days) decreased the activity of hepatic and renal glutamic oxalacetic and glutamic pyruvic transaminases (GOT, GPT) and alkaline phosphatase (ALP) accompanied by increase in the levels of serum GOT and GPT and urinary protein. Simultaneous administration of vitamin E (5 mg/kg, intramuscularly for 7 days) reduced these Cd induced biochemical alterations. The accumulation of Cd in blood, liver and kidney also decreased significantly upon co-exposure to vitamin E. The antioxidant property of vitamin E seems to be responsible for the observed protection of Cd intoxication. PMID- 1586467 TI - Cadmium in tobacco. AB - The present study was conducted to determine the cadmium level in tobacco planted in five main tobacco-producing areas, a cadmium polluted area, and in cigarettes produced domestically (54 brands). The results indicate that average cadmium content in tobacco was 1.48 (0.10-4.95 mg/kg), which was similar to that of Indian tobacco (1.24 mg/kg), but the cadmium of tobacco produced in the cadmium polluted area was quite high (8.60 mg/kg). The average cigarette cadmium was 1.05 micrograms/g (with filter tip) and 1.61 micrograms/g (regular cigarette). Therefore special attention should be paid to the soil used in planting tobacco. PMID- 1586468 TI - Protective effect of schisanhenol against oxygen radical induced mitochondrial toxicity on rat heart and liver. AB - Schisanhenol (SAL) had been shown to have potent antioxidant activities. The protective effects of SAL against oxygen radical induced mitochondrial injuries of rat heart and liver were investigated in the present study. The ferrous cysteine induced mitochondrial lipid peroxidation was significantly inhibited by SAL, while the loss of ATPase activity induced by the lipid peroxidation was prevented. The rigidification of mitochondrial membrane, as well as swelling, lysis and disintegration of the mitochondria induced by ferrous-cysteine were all significantly inhibited by SAL. These results further confirm that SAL possesses antioxidant activity. PMID- 1586469 TI - Impact of spectral quality on toxicity of iron in Anabaena doliolum and Chlorella vulgaris. AB - Evidence is presented on the effects of low and high concentrations of iron on growth, nutrient uptake (NH+4 and NO3-), photosynthesis (CO2-fixation and O2 evolution) and nitrate reductase (NR) activity of A. doliolum and C. vulgaris under monochromatic irradiation. Control cultures (not treated with FeCl3) showed maximum growth under fluorescent followed by red, yellow, blue and green lights (fluorescent greater than yellow greater than red greater than blue greater than green). The inhibition was of synergistic type under yellow and red lights at all the iron concentrations tested. However, under blue and green lights the interaction was less than additive type. All the processes studied responded in a similar manner to a particular color of light. Under fluorescent light at low Fe concentrations, stimulation of NR, 14CO2-fixation and O2-evolution was noticed in both the test organisms. However, even the lowest concentration of iron tested was inhibitory to these processes under yellow and red lights. Under blue light at 20 micrograms.ml-1 Fe, NR activity was inhibited by 98%. This study clearly demonstrates that metal toxicity to phytoplankton will be greatly affected by spectral quality, hence it will have great significance in limnological research. PMID- 1586470 TI - Effects of lead exposure on porphyrin metabolism indicators in smelter workers. AB - A study on the dose-effect relationship between blood lead level and FEP, ZPP, CPU, and ALAU among 250 lead smelter workers was conducted. A nonlinear regression model of a dose-effect relationship between blood lead and porphyrin metabolism indicators was established. The upper limit of normal values of these indicators were estimated from blood lead levels by these nonlinear regression equations. The diagnostic significance was evaluated by multiregression and discriminant analysis. This study would be helpful to the decision-making policy in revising the current diagnostic criteria for occupational lead poisoning. PMID- 1586471 TI - Immunohistochemical localization of peptidylarginine deiminase in the rat brain. AB - The enzyme peptidylarginine deiminase is responsible for the post-translational modification of certain proteins by catalysing the deimination of arginine residues to citrullines. Recently, peptidylarginine deiminase has been purified from rat skeletal muscle and its primary structure determined by molecular cloning. We have used antibodies raised against this enzyme to examine its distribution in the rat central nervous system. A few discrete neuronal cell groups in the telencephalon were selectively stained. These were the septofimbrial nucleus, the anterior commissural nucleus of the hypothalamus, and the anterodorsal thalamic nucleus. The subcommissural organ was intensely stained; but other circumventricular organs were not. In addition, peptidylarginine deiminase-immunoreactivity was found in a large population of small cells throughout the grey and white matter of the rat brain. Some of these cells contained glial fibrillary acidic protein and could thus be identified as astrocytes. However, in many regions these peptidylarginine deiminase-positive cells appeared distinct from the glial fibrillary acidic protein-positive astrocytes. Light and electron microscopic examination indicated that these cells had the morphology of microglia, however they were not stained by a lectin marker for microglia. These cells often surrounded cerebral capillaries, and sent ramifying processes into the neuropil. Peptidylarginine deiminase has been suggested to be involved in the synthesis of the endothelium-derived relaxing factor nitric oxide from arginine-containing molecules. Thus the distinct peptidylarginine deiminase-positive glial cells surrounding cerebral blood vessels may be in a position to regulate local blood flow in response to neuronal activity. PMID- 1586472 TI - Diazepam binding inhibitor processing in the rhesus monkey brain: an immunocytochemical study. AB - Immunocytochemical methods were used to study the regional and cellular distribution of diazepam binding inhibitor (DBI)-, ODN (DBI 33-50)- and TTN (DBI 17-50)-like immunoreactivity (LI) in monkey brain. DBI-, ODN- and TTN-LI were found to have similar regional but different cellular distributions. The most intense staining was detected in limbic structures, especially the amygdala. The most notable staining discrepancy was the weak-to-moderate uniform DBI-LI and the very high patchy ODN-LI and TTN-LI in the ventral striatum. At the cellular level, DBI-LI was preferentially localized in glia-like cells, whereas ODN-LI and TTN-LI were mainly found in neurons. PMID- 1586473 TI - An intriguing pitfall in chemical neuroanatomy: specific populations of unspecifically immunoreactive neurons in the brain of the mormyrid fish Gnathonemus petersii. AB - The present paper describes the location, morphology, ultrastructure and immunocytochemical properties of neurons in the brain of the mormyrid fish Gnathonemus petersii, that appear to be unspecifically immunoreactive to a number of secondary or tertiary antibodies used in immunohistochemical procedures, including rabbit-anti-mouse immunoglobulins (IGGs), rabbit peroxidase-anti peroxidase IGGs, and rabbit-anti-sheep or sheep peroxidase-anti-peroxidase IGGs. Unspecifically immunoreactive (UI) cells have typically neuronal morphological and ultrastructural characteristics, and occur at four specific locations in the mormyrid brain. A small rhombencephalic group is located rostrolateral to the efferent octaval nucleus, between the fasciculus longitudinalis medialis and the decussation of the lateral lemniscus. A mesencephalic cluster of cells is located in the dorsal midbrain tegmentum against the tractus telencephalo mesencephalicus. In addition, dispersed UI neurons were observed in the nucleus lateralis of the torus semicircularis and in the preoptic region above the optic chiasm. Remarkably, UI cells are clearly present in a substantial number of brains investigated, but not detectable in others. The present findings point to a curious pitfall in chemical neuroanatomy, the functional significance of which is unknown at present. In several previous studies using the brain of G. petersii, UI cells were abusively included in the description of monoaminergic cell groups. Similar cells have until now not been reported in other vertebrate brains. PMID- 1586474 TI - A comparative study of protein immobilization techniques for optical immunosensors. AB - This paper presents the results of a study of a number of antibody immobilization techniques for application to optical immunosensors. In particular, well-known methods such as covalent binding and physical adsorption have been extended to the Langmiur-Blodgett method in an attempt to improve the density and possibly the uniformity of orientation of monoclonal antibodies on an optical surface. The surface density of active immobilized antibodies was determined from enzyme immunoassay and their thickness and refractive index were deduced from ellipsometry. It is shown that, although high surface densities (500 ng/cm2) of antibody can be obtained, the major obstacle to the detection of low concentrations of antigens or haptens is the non-specific binding of foreign molecules to the sensing surface. PMID- 1586475 TI - Product guide/1992. PMID- 1586476 TI - Origin and evolution of the vertebrate immune system. AB - The immune system is a complex evolutionary unit and it would be simplistic to conclude that the immune systems of all primitive vertebrates are primitive. Because of the large number of elements involved, many evolutionary events must have taken place, some of them neutral, some of them selected, to constitute the systems that we are looking at towards the end of the 20th century. All these systems have perhaps evolved beyond the apparent evolutionary state of the species in which they are found. They have been modulated by factors linked not only to the internal evolution of their elementary genes, but also by coevolution with factors in the internal environment, such as cellular constraints, metabolism, mode of reproduction and progeny size. It seems that good inventions are long lasting, which is the reason why some elements of the invertebrate immune system can be found with similar functions in vertebrates (defensins). It is also the reason why Ig domains have been exploited in so many ways, whether for the immune system or not. Again, they had an evolution of their own. The comparative study of the immune systems carried out on the occasion of this phylogenetic survey shows a world particularly dynamic and diverse. The comparisons between the solutions chosen by the various phyla of the animal kingdom, or closer to us by the various classes of vertebrates, allow us to distinguish the essential features of the immune system. From this viewpoint, this approach is not only of phylogenetic interest, but also has an applied aspect. Increasing our knowledge in this area could help suggest solutions to clinicians when they are faced with deficiencies and abnormalities in the immune system of man. PMID- 1586477 TI - Vaginal leukocyte characteristics in urogenital trichomoniasis. AB - Morphological and functional characteristics of vaginal exudate leukocytes were examined in 47 patients with urogenital trichomoniasis. Electron microscopic morphology, viability, phagocytosis of Candida albicans blastospores and ability to undergo respiratory burst in the iodonitrotetrazolium reductase test were evaluated in these cells. Vaginal inflammatory leukocytes were almost exclusively polymorphonuclear neutrophils, and their concentration was positively correlated (r = 0.58; p less than 0.001) with the number of trichomonads in the exudate. Median leukocyte viability reached 39% and both phagocytic and tetrazolium reductase activities of these cells were significantly reduced in comparison with those of circulating polymorphonuclear leukocytes. Patients with a clinical picture of severe mucosal inflammation had significantly higher vaginal exudate leukocyte concentrations and viability than those without inflammatory signs. The possible role of vaginal leukocytes in the pathogenesis of urogenital trichomoniasis is discussed. PMID- 1586478 TI - Effect of anti-interleukin-1 administration to rats with adriamycin-induced nephrosis. AB - Rats receiving a single dose of adriamycin (7.5 mg/kg) develop heavy proteinuria and histologic lesions similar to those found in minimal change nephrotic syndrome in humans. We found that whole isolated glomeruli from rats injected with adriamycin secreted an IL-1-like cytokine which closely resembled macrophage IL-1. Maximal IL-1-like activity was detected on day 14 of the experiment when rats were heavily proteinuric. Administration of anti-IL-1 antiserum to rats with adriamycin-induced nephrosis provoked a transient but marked reduction in the urinary protein excretion. Our results indicate that IL-1-could be an important mediator implicated in the development of proteinuria in this experimental nephropathy. PMID- 1586479 TI - Phagocyte killing of Campylobacter jejuni in relation to oxidative activation. AB - When studying the interaction between Campylobacter jejuni and human neutrophils, we found that four different clinical isolates showed a great variability in this association. Also the ability to induce neutrophil production of oxidative metabolites, measured as chemiluminescence (CL), differed between the strains. Surprisingly, strain 1, which showed weak interaction with neutrophils and high resistance to killing, induced the highest CL response. All strains evoked an intracellular CL response, and three strains also gave rise to an extracellular response. This extracellular release of toxic oxygen species might contribute to the local tissue damage during infection. There was no clear correlation between association, killing and oxidative response. However, one strain that only evoked an intracellular generation of oxygen metabolites also showed the highest sensitivity to killing. Phagocytosis was increased up to ten times after opsonization with normal human serum. The intracellular CL production increased several fold, whereas the extracellular generation of oxygen species disappeared or was considerably decreased after opsonization. These results indicate that complement-opsonized C. jejuni are phagocytosed and readily attacked by the oxidative defence system within the phagosome. PMID- 1586480 TI - Plasma proteins in normal neurons. Immunohistochemical studies on autopsy material and experimental animals. AB - Previous observations have shown that plasma proteins are taken up by damaged neurons after trauma, cold injury and anoxic lesions. The present study was undertaken to test whether such uptake also can occur in normal neurons. Normal human brains at different intervals after death as well as normal rat brains after perfusion and immersion fixation were studied. During the first 24 h after death, the human cases showed practically no immunostaining with anti-fibrinogen and vague and inconstant staining with anti-albumin in the cortex and hippocampus, while certain brain stem nuclei were stained with both antisera even at the shortest postmortem intervals. At longer intervals, increased immunostaining of the neurons in the cortex and hippocampus was also demonstrated. Generally, more cells were positive for albumin than for fibrinogen. Perfusion-fixed rat brains showed no immunostaining, whereas rat brains that were immersion-fixed 24 h after death showed positive staining, mainly located in the brain stem. It is concluded that the staining of normal neurons demonstrated with the present method is due to postmortem leakage of proteins. Since practically no uptake of fibrinogen occurs in the cortex or hippocampus during the first 24 h, a definite neuronal staining with anti fibrinogen at these intervals probably indicates true neuronal damage. In the brain stem, on the other hand, this phenomenon can not be used to demonstrate neuronal damage even at the shortest postmortem intervals. PMID- 1586481 TI - Proliferative myositis and fasciitis. A light and electron microscopic, cytologic, DNA-cytometric and immunohistochemical study. AB - Two cases of proliferative myositis, four cases of proliferative fasciitis and one mixed form of proliferative myositis and fasciitis have been analyzed in terms of cell differentiation and DNA content. Light microscopically, the lesions were characterized by a mixture of proliferating spindle-shaped cells and uni-, bi- or occasionally multinucleated ganglion cell-like cells. The spindle cells showed ultrastructural features and immunohistochemical properties, including an immunoreactivity for smooth muscle-specific actin, indicative of a myofibroblastic differentiation. The ganglion cell-like cells displayed some resemblance to active osteoblasts ultrastructurally and differed immunohistochemically from the spindle cells by being non-immunoreactive for smooth muscle-specific actin. None of the two cell types showed immunoreactivity for desmin, myoglobin or factor VIII RAG. It is suggested that the two cell types represent different lines of cell differentiation. The cytologic features in smears, as seen in two cases of proliferative fasciitis and one case of proliferative myositis, are considered to be characteristic of these lesions and to permit the diagnosis to be made by fine-needle aspiration. In two of the cases, the lesion was diagnosed only cytologically and thereafter disappeared spontaneously within a month. Cytometric DNA measurements, using two different image analysis systems on Feulgen-stained sections and smears, revealed a "diploid" spindle-shaped cell population with a variable proportion of cells with scattered DNA values. The ganglion cell-like cells differed from the spindle cells by having a broad DNA peak in the diploid region and additional peaks in the tetraploid region, as well as a higher proportion of cells with scattered DNA values compared with those of the spindle-shaped cells. The results of the quantitative DNA analysis are well in keeping with the benign and proliferative nature of these lesions. However, with the technique used here, quantitative DNA analysis, does not distinguish these pseudosarcomatous fibrous lesions from diploid and tetraploid soft tissue sarcomas. PMID- 1586482 TI - Early development in healthy children of serum opsonins against nonpathogenic Neisseria meningitidis. AB - In an earlier study, with the use of chemiluminescence (CL) and phagocytic killing, we could show that in the presence of serum from healthy adults polymorphonuclear leukocytes (PMNL) efficiently handle nonpathogenic Neisseria meningitidis strains, in sharp contrast to those associated with clinical disease. The major part of this difference was dependent on serum factors. In the present study 84 serum samples from children 1-3, 4-6, 7-9, and 10-14 years old were studied by the CL technique according to their ability to opsonize meningococci. There was a highly significant difference (p less than 0.001) in all four age groups when the CL indexes obtained with the pathogenic meningococci of the serogroups A, B and C were compared with those of the nonpathogenic menigococci: serogroup 29E and nongroupable meningococci. These findings imply that the ability to opsonize so-called nonpathogenic meningococci is developed early in life and may explain why they are only occasionally able to cause disease. PMID- 1586484 TI - Interferon-gamma may enhance infection of blood-derived macrophages with HIV-1 in the presence of HIV-positive serum. AB - HIV multiplication in blood-derived macrophages was slightly inhibited by pretreatment of cells with interferon-gamma or by preincubation of virus with serum containing antibodies against HIV. When these pretreatments were combined, the HIV titres observed a short time after infection were enhanced. This effect was blocked by antibodies against Fc receptors but not by antibodies against CD4 receptors. Interferon enhanced the expression of Fc receptors on macrophages. The results indicate that IFN-gamma, in appropriate combinations with HIV-antibody containing human serum, may enhance the rate of HIV infection of macrophages. PMID- 1586483 TI - Yersinia enterocolitica serotype 0:3-induced arthritis in mice: microbiological and histopathological information. AB - Gross anatomical and histopathological changes in arthritic joints resulting from oral challenge with Yersinia enterocolitica serotype 0:3, upon pretreatment with desferrioxamine, were always more severe than those induced by intravenous infection of immunized animals. In all the acute inflammation episodes studied, live Yersiniae were isolated from the arthritic region. Invariably, a heavy mixed infiltration of synovia, joint spaces and soft tissues was observed at this stage. Concurrent fibrous thickening and vascular proliferation, along with erosion of articular cartilages and anomalous bone regeneration, were also apparent. In spite of these significant facts, the bacterium could be histopathologically identified only in bone marrow where it developed microcolonies and caused significant necrosis as well. The live bacterium was also retrieved from two- and six-month-old arthritic ankles/paws examined, but it could not be seen in histological sections of joints. By this time, no cellular infiltration was evident, but there was extensive fibrosis. Bones were at times greatly enlarged, showing a spongeous-like structure. Additionally, articular cartilages could be completely lost and were substituted by an anomalous ossification filling the joint spaces. This situation led to bone fusion, resembling articular ankylosing traits. In summary, we present the first experimental evidence that Y. enterocolitica serotype 0:3 is a causal agent of osteoarthritis and osteomyelitis, and that it may survive for prolonged periods of time in osseous structures. PMID- 1586485 TI - Characterization of a 25,000-dalton Helicobacter pylori protein, cross-reacting with a Campylobacter jejuni protein. AB - Extract obtained by ultrasonic disruption of Helicobacter pylori bacteria contained a protein with subunit molecular mass of 25 kD which bound antibodies in sera from patients with H. pylori-associated disease. The protein was purified by gel permeation and elution from SDS-polyacrylamide gel slices, and was used to raise an anti-25-kD protein-specific rabbit serum. Using the antiserum in experiments, the results indicated the following: The protein exists as covalently linked dimers (45 kD) of the 25-kD subunits. Variable numbers of non covalently linked copies of the dimers make up the native protein. The protein was susceptible to digestion by papain, pronase, and trypsin. Pepsin cleaved off a fragment of approximately 2 kD. A small share of the protein was exposed at the bacterial cell surface, the greatest share being localized internally. The protein was not secreted and it was probably not an integral part of the outer membrane. It was produced in variable quantity by all of 11 H. pylori strains tested and was a major protein in some strains. A cross-reacting protein with subunit size of 25 kD was also produced by Campylobacter jejuni strains, but not by any of a variety of other bacteria. Since both H. pylori and C. jejuni infection occur with a high frequency. the cross-reacting 25-kD protein may interfere unfavourably with the diagnostic specificity of serological tests for infection caused by these bacteria. PMID- 1586486 TI - Growth cone guidance by floor plate cells in the spinal cord of zebrafish embryos. AB - The spinal cord of early zebrafish embryos contains a small number of neuronal classes whose growth cones all follow stereotyped, cell-specific pathways to their targets. Two classes of spinal neurons make cell-specific turns at or near the ventral midline of the spinal cord, which is occupied by a single row of midline floor plate cells. We tested whether these cells guide the growth cones by examining embryos missing the midline floor plate cells due either to laser ablation of the cells or to a mutation (cyc-1). In these embryos the growth cones followed both normal and aberrant pathways once near the ventral midline. This suggests that normally the midline floor plate cells do provide guidance cues, but that these cues are not obligatory. PMID- 1586487 TI - Potentiation of nicotinic receptor response by external calcium in rat central neurons. AB - Nicotinic acetylcholine receptor (nAChR) responses of rat medial habenular neurons are potentiated up to 3.5-fold by increasing the concentration of external Ca2+ in the millimolar range. This effect, independent of voltage, is probably due to the binding of Ca2+ to an external site. External Ca2+ decreases nAChR single-channel conductance at negative but not positive potentials, and it markedly enhances the frequency of opening of acetylcholine activated channels. The potentiating effect of Ca2+ is mimicked by Ba2+ and Sr2+, but barely by Mg2+. These data support the existence of positively acting allosteric sites for Ca2+, distinct from those involved in the decrease of single-channel conductance. A model in which external Ca2+ changes the properties of activation of the nAChR appears consistent with these data. PMID- 1586488 TI - Repulsion between tetraethylammonium ions in cloned voltage-gated potassium channels. AB - Tetraethylammonium ion (TEA+) blocks voltage-gated K+ channels by acting at two sites located at opposite ends of the aqueous pore. This allowed us to test two predictions made by models of ion permeation, namely that K+ channels can be simultaneously occupied by multiple ions and that the ions repel each other. We show that externally applied TEA+ antagonize block by internal TEA+ and vice versa. The antagonism is less than predicted for competitive binding, hence TEA+ may occupy both sites simultaneously. External TEA+ and internal TEA+ reduce each others affinity 4- to 5-fold. In addition, K+ antagonizes block by TEA+ at the opposite side of the membrane, and external TEA+ antagonizes is block by internal Ba2+. The antagonism between ions applied at opposite sides of the membrane may be common to all cations binding to K+ channels. PMID- 1586489 TI - TNF alpha, IL-1 alpha and bFGF are implicated in the complex disease of GM-CSF transgenic mice. AB - Transgenic mice aberrantly expressing the granulocyte-macrophage colony stimulating factor (GM-CSF) gene develop an unusual syndrome of blindness, tissue damage and wasting which is associated with accumulations of hemopoietic cells. In order to further characterize this disease state, we have used messenger RNA detection techniques to show that the genes for tumor necrosis factor (TNF alpha), interleukin-1 alpha (IL-1 alpha) and basic fibroblast growth factor (bFGF) are expressed at abnormally high levels in both macrophages and granulocytes in transgenic mice. Furthermore, since these cell types also express the GM-CSF transgene, it is likely that they are autocrine stimulated by GM-CSF. These observations raise the possibilities that, first, the expression of tumor necrosis factor alpha, interleukin-1 alpha and basic fibroblast growth factor in hemopoietic cells is a direct consequence of their autostimulation by GM-CSF, and second, that these cytokines may be responsible for some aspects of the transgenic mouse disease. PMID- 1586490 TI - Lung tolerance to hyperthermia by in vivo perfusion. AB - In vivo isolated lung perfusion is a novel technique for targeting anticancer therapy to the lung while avoiding systemic toxicity as normal lung toxicity from the antitumour therapy becomes the limiting factor. This study was performed to investigate the effects of hyperthermia on lung function in an intact animal model in which both acute and subacute toxicity could be monitored. Dogs underwent in vivo isolated lung perfusion. A control group was perfused to a lung temperature of 37 degrees C (group 1) and two other groups were treated in an identical manner except that the perfusion temperature was 43 degrees-44.8 degrees C in group 2 and greater than 45 degrees C in group 3. An assessment of lung injury was performed pre-perfusion, immediately post-perfusion and 2 weeks post-perfusion by measurement of extravascular lung water (Qev), serotonin uptake and wet weight to dry weight ratio. Our findings showed that the lung was tolerant to hyperthermia up to about 44 degrees C for 1 h. Analysis of 4 animals who survived perfusion above 3/44.0 degrees C showed a highly significant decrease in serotonin uptake between pre- and post-perfusion values (82.4 +/- 1.2 vs 40.4 +/- 3.9, P less than 0.02); at 2 weeks serotonin uptake had returned to normal in all 3 dogs. Fulminating pulmonary oedema developed at temperatures over 45 degrees C. Serotonin uptake may be a sensitive predictor of thermal lung injury. PMID- 1586491 TI - Decreased incidence of bronchial complications following lung transplantation. AB - Despite omental wrap and avoidance of prophylactic administration of corticosteroids in the early postoperative phase, ischemic bronchial complications still represent an important source of early morbidity and mortality following lung transplantation. In a retrospective analysis, the effect of pharmacological enhancement of pulmonary collateral flow on bronchial healing was investigated. Thirty-nine consecutive unilateral or bilateral transplant procedures (Tx) were analyzed. Immunosuppression consisted of rabbit antithymocyte globulin (RATG), cyclosporine A, and azathioprine. In group 1 (10 Tx, 12 anastomoses) routine immunosuppression was employed and the anastomoses wrapped with an omental or pericardial pedicle. In group 2 (29 Tx, 41 anastomoses) PGI2 (4 ng/kg per min x 48 h), heparin (200 U/kg per day), and prednisolone (0.5 mg/kg per day) were added to the therapeutic regimen. The 2 groups were comparable with respect to age and sex of the patients, primary diagnosis, type of transplant, intraoperative use of extracorporeal circulation, graft ischemia, duration of mechanical ventilation, and mortality. Bronchoscopic evidence of a significant bronchial ischemia (extending more than 1 cartilaginous ring beyond the anastomosis) was seen in 8 of 12 anastomoses in group 1 vs 14 of 53 anastomoses in group 2 (P = NS). In group 1, significant bronchial stenosis required implantation of an endobronchial silicone stent in 6 of 12 anastomoses, whereas in group 2, no significant bronchial stenosis occurred (P less than 0.01). No negative effects possibly related to the prophylactic administration of corticosteroids could be observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586492 TI - Treatment of thymomas. A report of 67 cases. AB - From 1979 to 1989, 126 patients were treated for thymic tumors. Of these, 67 (53%) had thymomas occurring in 27 men and 40 women; the mean age was 46 years: 24 patients had no symptoms and myasthenia gravis was present in 21 cases. A complete resection was performed in 45 patients, associated in 22 with postoperative adjuvant treatment (radiotherapy, 2; radio- and chemotherapy, 20). Two patients had a partial resection followed by radiotherapy and chemotherapy. Twenty patients had initially only a biopsy and were treated by irradiation in 3 cases, radio- plus chemotherapy in 16, radio- plus chemotherapy and subsequent resection in 1 case. The staging was carried out according to the GETT Classification (stage I A:26; I B:6; II:12; III A:1; III B:18; IVA:4). Thymomas were found to be of predominant epithelial type in 12 cases, predominantly lymphocytic type in 9, and mixed in 46. No recurrence occurred after complete resection. The overall 10-year survival was 71.1%. A good correlation was found according to staging: 96% in stage I; 80% in stage II; 35% in stage III. Presence of myasthenia gravis did not affect the results. The best prognostic factor remains complete resection with postoperative radiotherapy to prevent recurrences. The role of adjuvant chemotherapy needs further evaluation. PMID- 1586493 TI - Coronary artery bypass surgery with intermittent aortic cross-clamping. AB - Despite the generally accepted use of cardioplegia for myocardial protection during cardiac revascularization and other operations, non-cardioplegic methods have been used by many surgeons throughout the world. We have prospectively studied 229 patients consecutively subjected to isolated coronary artery bypass surgery from March 1990 to February 1991 by a single surgeon who used intermittent aortic cross-clamping for construction of the distal anastomoses. The mean age of the patients was 58.9 +/- 8.9 years. One hundred and nine patients (47.6%) with unstable angina were subjected to urgent or emergent surgery and 129 (56.3%) had a previous myocardial infarction. The mean number of grafts per patient was 3.0. The ischaemic time per graft was 6.5 +/- 1.4 min. At least one internal mammary artery was used in 98% of the cases (1.4 internal mammary artery grafts/patient). Hospital mortality was 0.9% (two patients, in neither case related to the procedure). Only nine patients (3.9%) required inotropes and none needed intra-aortic counterpulsation. The analysis of serum enzymes specific of myocardial lesion showed a CPK-MB/CPK ratio of 10.5 +/- 10.2 after surgery, 6.4 +/- 6.6% at 24 h after surgery, and 6.9 +/- 2.6% by the 5th day. Only four patients (1.7%) had ECG criteria of myocardial infarction. These results were compared retrospectively with those of the 40 immediately preceding patients (December 1989 to February 1990), in whom crystalloid cardioplegia had been used. There were no differences between the two groups with regard to age, prevalence of unstable angina and of previous myocardial infarction, and technique used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586494 TI - Superiority of endocardial versus epicardial implantation of the implantable cardioverter defibrillator (ICD). AB - The implantable cardioverter-defibrillator (ICD) has proved to be an efficient device for the treatment of severe ventricular tachyarrhythmias (VT). From May 1985 to August 1991, the ICD was implanted in 107 patients of whom 72% suffered from coronary artery disease, 17% from cardiomyopathy, 5% from long QT-syndrome and 6% from other heart disease. All patients had a life threatening episode of VT or at least one episode of ventricular fibrillation. Of 107 implants, 12% were combined with other heart surgery, 55% were isolated epicardial implantations (epi I) and in 33%, the novel endocardial (endo I) approach was chosen. Between epi I and endo I we found no difference in operation time, but time for ICU and in-hospital stay was significantly shorter using the transvenous approach. In addition, sensing and pacing capability of the endocardial screw-in electrode was superior and the need for thoracotomy was avoided, a particular advantage in patients with previous heart surgery. Complications after epi I were: temporary low cardiac output, 1; perioperative death, 2; infection, 3, and after endo I: electrode dislocation, 2. Hence, endo I may become the method of choice for patients without concomitant surgery. PMID- 1586495 TI - Cardiac denervation in the calf using cryoablation: functional evidence and regional tissue catecholamine content. AB - Twenty-six calves were subjected to a technique of cryoablation in order to establish an animal model of complete cardiac denervation. All 26 survived the procedure, and 20 were alive to be re-evaluated 2-4 weeks later. Mean heart rate in the denervated animals rose from 77 +/- 7.8 beats/min to 102 +/- 16.4 (P less than 0.01). Cryoablation abolished the heart rate responses to electrical stimulation of the vagus nerve and thoracic sympathetic trunk. The reduction in myocardial noradrenaline concentrations averaged 99% in the right atrium, 90% in the left atrium, 85% in the right ventricle and 90% in the left ventricle, when compared with tissue obtained from control animals. Cryoablation is a relatively simple means of accomplishing complete functional cardiac denervation in the calf. On the basis of the observed change in heart rate, the calf model appears to be more comparable with human heart transplant recipients than the dog. PMID- 1586496 TI - Protective effects of the Hemopump left ventricular assist device in experimental cardiogenic shock. AB - The efficacy of the new cable-driven rotating left ventricular assist device Hemopump in cardiogenic shock was examined in experiments with adult sheep (n = 14; body weight 50-71 kg). Shock was induced by high frequency ventricular pacing. Aortic, pulmonary, central venous and left ventricular pressures as well as electromagnetic measurements of coronary blood flow were recorded continuously; cardiac output was measured by thermodilution technique. Blood samples for determination of oxygen content, electrolytes and lactate were taken under control conditions, in shock, and during pump intervention at different levels of pump speed. Vascular resistance, total body and myocardial oxygen consumption as well as myocardial uptake and release of lactate were calculated. High frequency pacing led to a significant decrease in cardiac output (from 3.8 +/- 0.8 to 2.2 +/- 1.6 l/min), mean aortic pressure (89.1 +/- 14.4 to 47.6 +/- 7.2 mmHg), and total body oxygen consumption (2.6 +/- 0.3 to 1.4 +/- 0.7 ml/min per kg), as well as myocardial release of lactate (arterial coronary-venous difference of lactate: 0.27 +/- 0.26 to -0.32 +/- 0.72 mmol/l). Hemopump assist in this condition resulted in a significant increase in cardiac output (to 2.8 +/ 0.6 l/min), mean aortic pressure (to 65.6 +/- 13.9 mmHg), and myocardial perfusion pressure (from 25.5 +/- 11.0 to 59.0 +/- 14.7), and led to nearly normal total body oxygen consumption (2.5 +/- 0.7 ml/min per kg), a decrease in myocardial oxygen consumption (from 6.1 +/- 2.1 in shock, to 4.8 +/- 1.7 ml/min per 100 g), and to normal arterial coronary-venous difference of lactate (0.24 +/ 0.26 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586497 TI - Carcinoma developing in the neo-oesophagus following gastroplasty. AB - Carcinoma developing after gastroplasty and fundoplication has been documented in only five cases. We report a further case occurring in a patient 4 years after initial surgery. The tumour originated in the newly created tubular extension. There was no evidence of a columnar lining in the true oesophagus prior to surgery. The development, technique and complications of gastroplasty and partial fundoplication are discussed with special mention of the diagnostic problems when a tumour develops in a patient who has undergone this procedure. PMID- 1586498 TI - Effect of warm ischemia following harvesting of allograft cardiac valves. PMID- 1586499 TI - Comparative study between the gastroepiploic and the internal thoracic artery as a coronary bypass. PMID- 1586500 TI - Continued surveillance of cancer incidence among Swedish smelter workers. AB - A cohort study of workers at a smeltery in northern Sweden showed an excess mortality, mostly due to deaths in cancer (especially in the respiratory organs) and circulatory diseases. Further follow-up of the cohort showed a decreasing trend in lung cancer incidence and mortality. The cohort studied has now been expanded and comprises 6,334 blue-collar workers first employed 1928-1979. They were followed in the cancer register up to 1987-01-01 and in the cause-of-death register up to 1988-01-01. The decreasing trend in lung cancer incidence and mortality continued but there was still an elevated lung cancer incidence among the workers when compared with Swedish males. The cumulative occurrence of lung cancer since time of first employment was analyzed by different employment cohorts and a higher occurrence of lung cancer was found among those earlier employed. PMID- 1586501 TI - Prognostic significance of axillary nodal status in primary breast cancer in relation to the number of resected nodes. Stockholm Breast Cancer Study Group. AB - The prognostic significance of the number of metastatic axillary lymph nodes in relation to the number of identified nodes among 1,622 patients with operable breast cancer was assessed. We present a Cox's analysis of the prognostic significance of nodal status in relation to loco-regional recurrence, axillary recurrence, distant metastasis and death due to breast cancer respectively. As expected, the relative risks were generally higher for patients with nodal involvement, particularly those with 4 or more positive nodes or with few examined nodes. However, among those with more than 4 positive nodes the risk of distant metastases and death due to breast cancer was about the same irrespective of the number of nodes examined. PMID- 1586502 TI - Microvascular corrosion casting of normal tissue, transitional mucosa and adenocarcinoma in the human colon. AB - The microcirculatory architecture of normal tissue, transitional mucosa and adenocarcinoma of the human colon was investigated with microvascular corrosion casting (MVCC) combined with scanning electron microscopy (SEM). The study showed that the capillaries within the normal mucosa were arranged in a regular hexagonal pattern around the mucosal glands and that the microvessels of transitional mucosa mostly had lost the typical hexagonal pattern and become slightly wider in diameter. The microvessels in the tumor periphery were increased in number and disorganized, and presented large variation in morphology with claw-like formations, widened sinuses, diverticula and appendixoid patterns. Microvessels were lacking in the central areas of tumors. These morphological alterations may serve as additional indicators of tumor development. PMID- 1586503 TI - Bone marrow examination in Hodgkin's disease. AB - Bone marrow aspiration and biopsy was performed as part of routine staging in 425 patients with primary Hodgkin's disease. Only seven patients were found to have bone marrow disease by biopsy and only four by aspiration. All these patients had B symptoms and stage III or IV before bone marrow examination. Bone marrow infiltration did not influence treatment decision and there was no association between bone marrow findings and outcome of the disease. PMID- 1586504 TI - Radiotherapy and verrucous carcinoma of the oral cavity. A study of 107 cases. AB - One hundred and seven cases of oral verrucous carcinoma treated primarily with radiotherapy at Kasturba Hospital, Manipal, India between 1977 and 1987 were analysed concerning location within the oral cavity, clinical extent, and effectiveness of radiotherapy. The most common site was the buccal mucosa followed by the buccogingival sulcus. Only 13.2% of the patients presented with T1 or T2 tumours and 32.7% had clinically negative nodes. Biopsy had to be repeated more than once in 22 patients to get confirmation of invasive carcinoma. The 5-year survival rate was 35% for stage III and 26% for stage IV. The treatment results with radiotherapy were comparable with those for ordinary squamous cell carcinoma of the oral cavity. It is felt that the treatment policy for verrucous carcinoma can be the same as for ordinary squamous cell carcinoma. In order to prevent delay in diagnosis and treatment, proper cooperation between the treating oncologist and the pathologist is essential. PMID- 1586505 TI - Postoperative radiotherapy of squamous cell carcinoma of the tonsil. Factors influencing survival and time to recurrence. AB - From 1970 to 1988, 40 patients with squamous cell carcinoma of the tonsillar region were treated with surgery and postoperative split-course radiotherapy. The 5-year survival rate for all the patients was 52.5%; the corresponding figure was 100% in stage I, 75% in stage II, 63% in stage III and 15% in stage IV. The local control rate was 100% in stage I, 89% in stage II, 87% in stage III and 38% in stage IV. In the proportional hazards regression analysis T- and N-category and pretreatment Karnofsky index had the strongest association to survival, whereas T and N-category and total radiation dose were most strongly associated to time to recurrence. PMID- 1586506 TI - Effect of dipyridamole, theophyllamine and verapamil on spontaneous in vitro proliferation of myelogenous leukaemia cells. AB - Dipyridamole strongly inhibited spontaneous in vitro proliferation of peripheral blood mononuclear cells from patients with acute myelogenous leukaemia (n = 9), chronic myelogenous leukaemia in first chronic phase (n = 4) and blast phase (n = 1). Theophyllamine and verapamil also inhibited proliferation of leukaemia cells from all patients except the CML patient in blast phase where only minimal inhibition was seen. Only dipyridamole caused strong inhibition in concentrations corresponding to the therapeutic serum level, and this inhibition was not influenced by the presence of high levels of interleukin 2. PMID- 1586507 TI - Leukemia after 131I treatment of thyroid cancer--comments on the article 'Second cancer following chemotherapy and radiotherapy--an epidemiological perspective' by J. Kaldor. PMID- 1586508 TI - Interpretation of granulomatous lesions in malignancy. AB - In patients with malignancy the most frequent granuloma-associated conditions are tumor-related sarcoid reactions, sarcoidosis, tuberculosis and other infections. Quite often, the finding of granulomatous lesions in patients with cancer may lead to difficulties of interpretation resulting in inappropriate treatment of both granulomatous disease and malignancy. This problem is reviewed and exemplified by a number of typical case histories. A systematic diagnostic approach must integrate anamnestic, clinical, histomorphological, immunohistological and laboratory information. In addition, prolonged follow-up may be necessary in order to establish the true nature of a granuloma-associated condition. PMID- 1586509 TI - Choriocarcinoma. A model for tumour markers. AB - Human chorionic gonadotrophin (hCG) was the first major tumour marker to be identified and in gestational choriocarcinoma remains the closest we have to the ideal indicator of tumour activity. What is measured in assays for this substance is however a complex subject which has to be understood if misinterpretation of the data is to be avoided. It is also necessary to understand the pathology and natural history of the spectrum of hCG producing tumours. The distinction between luteinising hormone (LH) and hCG only became possible with the production of antisera predominantly directed at the beta subunit of hCG. Since then monoclonal antibodies directed at restricted epitopes have revealed that a range of hCG fragments contribute to what is measured. Within the spectrum of hCG producing lesions are those that are self-terminating whilst others are premalignant, malignant but responsive to chemotherapy, or refractory to all present agents. Awareness of this complexity is essential for interpretation of values. For patients with hydatidiform mole hCG measurements form the basis of identifying progressive lesions and thus constituting a still unique biochemical screening programme for cancer. Its roles in diagnosis, prognostication, monitoring the course of the disease and in follow-up for detection of recurrence are unique in many respects. Although hCG measurements provide information critical to the management of each of these lesions that information can only be properly understood through an understanding of the pathological entities involved and the pharmacokinetics of hCG metabolism and excretion. PMID- 1586510 TI - [Surgical treatment of ischemic heart disease using internal thoracic artery and partial ileal bypass]. AB - The authors recommend complex two-stage treatment of ischemic heart disease, including a reconstructive operation on the coronary arteries and an operation for correcting the disturbed plasma lipid spectrum (partial ileal bypass). The results of operative treatment of 150 patients with the use of the internal thoracic artery were studied. The authors emphasize the advantages of this operation over one using an autovein graft. Complex operative treatment was conducted in the clinic in 60 patients with a good clinical effect. The authors also recommend operation for partial ileal bypass as an independent intervention in dyslipoproteinemia and diffuse affection of the coronary arteries. PMID- 1586511 TI - [Risk factors and methods of prevention of complications in digestive organs after myocardial revascularization in patients with generalized atherosclerosis]. AB - The clinico-hemodynamic and angiographic findings in 66 patients with ischemic heart disease were analysed to identify the risk factors of complications in the digestive system and to determine the methods for their prevention after myocardial revascularization. It was found that complications in the gastrointestinal tract develop after extracorporeal circulation more often in patients with lesions of the visceral branches of the abdominal aorta than in those without them. With purposeful preventive therapy and observance of definite precautions before, during, and after the operation, the incidence of complications in abdominal organs and the organs of the retroperitoneal space reduced to one fourth while the nature of these complications was less aggressive. This was confirmed by no postoperative deaths in the group of patients who had undergone preventive treatment. PMID- 1586512 TI - [Evaluation of the diagnostic effectiveness of the indicators of left atrial myocardial function in intraoperative cardiac weakness in patients with mitral valve defects]. AB - Excursions of the left-atrial myocardium were recorded by tensiometric transducers in patients with mitral valvular disease. The structural features of myocardial excursions were evaluated as symptoms. Myocardial shortening in P-Q interval was considered a negative symptom in relation to heart weakness, shortening in T-Q interval as an indefinite symptom, and shortening in Q-T interval as a positive symptom. Appraisal of the sensitivity and specificity of these symptoms revealed their high diagnostic efficacy. PMID- 1586513 TI - [Antibacterial prophylaxis in heart surgery interventions with extracorporeal circulation]. AB - Clinico-laboratory studies were conducted in 30 patients who underwent operations for heart diseases and thromboembolism of the pulmonary artery under extracorporeal circulation. Gentamicin and tobramycin were used for antibacterial prophylaxis. Study of the pharmacokinetics of the agents disclosed essential changes of the distribution volume and clearance of the antibiotics in the patients of the studied group, which made the routine regimen of their administration modified. Analysis of the results of administration of the agents according to a modulatory regimen showed its high prophylactic efficacy in the absence of side effects. PMID- 1586514 TI - [Functional state of the myocardium in patients with renovascular hypertension]. AB - The authors studied the changes in the mass and contractile function of the myocardium in 24 patients with vasorenal hypertension before operation and in the late periods after surgical correction of the renal blood flow. It was found that in vasorenal hypertension the mass of the myocardium doubled while its contractile and pumping functions diminished. In the late periods after adequate surgical correction of renal blood flow with a good hypotensive effect hypertrophy of the myocardium regresses and its contractile function improves. PMID- 1586515 TI - [Surgical-drug therapy aspects of the treatment of patients with obliterating thromboangiitis of the lower limbs]. AB - Standard operative interventions (thromboendarterectomy, (autovenous shunt) in patients with thromboangiitis obliterans of the lower limbs produce a poor effect. This is explained both by a poor initial condition of the draining channels and by advancement of the primary thromboangitic affection of the vascular wall in the zone of the intervention with its development into a stenotic-occlusive process. The use of some technical (operative) innovations, particularly postoperative arterial infusion of suspended forms of immunosuppresive agents (hydrocortisone, Kenalog), increased essentially the efficacy of restorative operations on the vessels with a high level of limb preservation and patency of the vessels which had been operated on. PMID- 1586516 TI - [Clinical aspects, diagnosis and surgical treatment of rupture of the mitral valve chordae]. AB - The authors generalize experience in surgical treatment of 121 patients with mitral incompetence caused by rupture of the chordal threads. Prosthetics of the mitral valve was conducted in 103 patients, plastic correction--in 18 patients. Study of the etiomorphological aspects of the problem showed destruction of the fibrous framework of the chorda to be a compulsory component of rupture of the chordae of various origin. At the same time, there are some similar clinico diagnostic manifestations of rupture of the chordae, which allows this form of mitral valvular disease to be set apart as an independent syndrome. Echocardiographic study is the most informative method in the diagnosis of the disease, it reveals rupture of the chordae in over 95% of cases. The immediate and late-term results of plastic operations and prosthetics were compared. Plastic operations are preferable in a favorable situation because survival after them is higher and thromboembolism does not develop even if anticoagulant therapy is not applied. PMID- 1586517 TI - [Intravascular laser irradiation of blood in multimodal treatment of patients with obliterating diseases of the lower limb vessels]. AB - The work analyses the results of the multimodality treatment of 80 patients among whom 20 suffered from endarteritis obliterans and 60 from atherosclerosis obliterans of the lower limb vessels. In the process of complex treatment intravascular laser irradiation of blood (ILIB) was carried out by introducing the light guide into a peripheral vein. In 31 (73.8%) patients with decompensated circulatory disorders in the limbs, a course of ILIB produced a good clinical effect. A positive effect was encountered in 35 (92.1%) of patients with subcompensated circulatory disorders in the lower limbs. The clinical efficacy of ILIB is due to normalization of blood coagulative properties, increase of the fibrinolytic potential, improvement of hemorheology, and normalization of the lipoprotein ratio. PMID- 1586518 TI - [Surgical treatment of lung cancer extending into the thoracic wall]. AB - In the Department of Surgery of Lungs and Mediastinum, National Research Centre of Surgery, USSR AMS, 88 patients underwent operation for lung carcinoma extending into the thoracic wall (which accounted for 2.6% of all patients who were operated on for carcinoma of the lungs) from 1963 to December 1990. Surgical treatment of such patients is the method of choice. The performance of both radical and palliative operations is expedient. The survival of patients after operation is determined by the depth of invasion of the thoracic wall by lung carcinoma and the condition of intrathoracic lymph nodes. PMID- 1586519 TI - [Reoperation in primary malignant tumors of the lung operated earlier]. AB - Retrospective analysis of 3,441 operations carried out in the Department of Pulmonary and Mediastinal Surgery, National Research Centre of Surgery, USSR Academy of Medical Sciences, from 1963 to 1990 for carcinoma and other malignant tumors of the lung showed that in 19 (0.6%) patients surgical interventions had been conducted on the same lung. Nonspecific pulmonary diseases, tuberculosis, and localized pneumosclerosis proved to be the most common diseases for which the first thoracotomy was performed. The number of such patients is continuously growing, in view of which the authors set them apart into an independent group of patients subjected to repeated operations in lung carcinoma. Approximately in half of these patients (47.4%) the malignant tumor occurred in the lung 8 years and more after the operation carried out for a benign disease; in the others (52.6%) the tumor existed in the lung at the first operation but was not removed due to diagnostic and tactical errors or was a latent carcinoma. It is concluded that timely and proper use of diagnostic methods and a high oncological alertness even during an operation for a benign disease may facilitate improvement of the results of surgical treatment of this category of patients with lung carcinoma. PMID- 1586520 TI - [First experience in the treatment of bronchial asthma by resection of the superior laryngeal nerve]. AB - Operations were conducted on 21 patients for bronchial asthma. Four of them suffered from the hormone-dependent form of the disease. The duration of the disease ranged from 12 months to 18 years. The operations were performed under local anesthesia through a left approach. The internal branch of the superior laryngeal nerve was exposed and identified and a segment of it was resected. The immediate results were positive in 16 cases, no effect was produced in 5 patients. The positive results were confirmed by clinical data and spirometry. PMID- 1586521 TI - [Effects of surgical complications on trace element metabolism in patients with cardio-esophageal and esophageal cancer]. AB - The homeostatic features of trace elements were studied in 48 patients with cardio-esophageal and esophageal carcinoma in development of incompetence of the anastomosis sutures (17), peritonitis (19), and intestinal fistulas (12). The level of the trace elements was determined in the red cells, blood plasma, and urine by emission plasma spectrometry. With the development of surgical complications after operation on the stomach and esophagus, the metabolism of trace elements was sharply disturbed, catabolic processes prevailed and were manifested by the escape of essential trace elements from the cells and their excretion in the urine. The changes of trace elements metabolism were more profound in peritonitis and intestinal fistulas. Complex intensive therapy including artificial feeding corrected partly the metabolic disorders. PMID- 1586522 TI - [Congenital esophageal cysts]. PMID- 1586523 TI - [Indications and counterindications of aortocoronary bypass]. AB - The author systematized the indications for aortocoronary shunting in ischemic heart disease on the basis of complex evaluation of the patient's condition with obligatory consideration for the clinical picture of the disease, the condition of the coronary channel, and the left ventricular myocardium. An absolute indication for the operation is Functional Class II-IV angina pectoris with multiple affection of the coronary channel or stenosis of the trunk of the left coronary artery and maintained or moderately diminished function of the left ventricle. Radiologically-guided endovascular dilatation of the narrowing is first indicated for patients with stenosis of one or two coronary arteries. The main principle in operation in ischemic heart disease is attainment of complete revascularization of the myocardium by shunting all arteries measuring more than 1 mm in diameter which are stenosed by 50% and more. The main contraindications for the operation on the part of the heart are diffuse or distal affection of the coronary arteries, a more than two-fold reduction of ejection fraction as compared to the normal value, Stage IIB-III circulatory insufficiency. PMID- 1586524 TI - Relationship between the number of partners in a general practice and the number of different drugs prescribed by that practice. AB - The objective of this study was to assess whether practice size, as measured by the number of doctors, had any bearing on the range of drugs prescribed. All practices in the northern and western health boards in Northern Ireland were included in the study--a total of 132 practices (362 doctors) serving a population of 628,249. Prescribing data, obtained from the Department of Health and Social Services (Northern Ireland) information technology unit database, were analysed retrospectively for the month of January 1989. The number of different preparations prescribed in each of 22 therapeutic groups were counted. Hence a measure of the range of prescribing was assessed. A significant correlation was found between the number of different preparations prescribed and the number of general practitioners working in the practice. However, no correlation was found between the number of different drugs prescribed and the mean prescribing cost per patient or the mean list size of the doctors in each practice. The use of a practice prescribing policy was found to have no influence on the range of drugs prescribed, nor on the prescribing costs. The inference is that formal therapeutic policies may be difficult to implement within group practices. These results are of importance to general practitioners since the greater the number of different drugs prescribed the greater will be the risk of side effects and dangerous interactions. PMID- 1586525 TI - Cost effectiveness of minor surgery in general practice: a prospective comparison with hospital practice. AB - The cost effectiveness of general practitioners undertaking minor surgery in their practices was determined in a prospective comparison of patients having minor surgery undertaken in five general practices over a 12 week period in 1989, and in the departments of dermatology and general surgery in Rotherham District General Hospital over a contemporaneous eight week period. There were no differences between the settings in the reported rates of wound infection or other complications and only one general practice patient was subsequently referred to hospital for specialist treatment. General practitioners sent a smaller proportion of specimens to a histopathology laboratory than hospital doctors (61% versus 90%, P less than 0.001); incorrectly diagnosed a larger proportion of malignant conditions as benign (10% versus 1%, P less than 0.05) and inadequately excised 5% of lesions where this never happened in hospital (difference not significant). General practice patients had shorter waiting times between referral and treatment, spent less time and money attending for treatment and more of them were satisfied with their treatment. The cost of a procedure undertaken in general practice was less than in hospital--pounds 33.53 versus pounds 45.54 for the excision of a lesion and pounds 3.00 versus pounds 3.22 for cryotherapy of a wart (1989-90 prices). Performing minor surgery in general practice would seem cost effective compared with a hospital setting. However, the risk of general practitioners inadequately excising a malignancy and not sending it to a histopathology laboratory must be addressed and the conclusion regarding cost effectiveness only applies where general practice is a substitute for the hospital setting and not an additional activity. PMID- 1586526 TI - Patient compliance with colorectal cancer screening in general practice. AB - A randomized controlled trial to test patient compliance with screening for colorectal cancer in association with general practice health checks was carried out in six practices (three urban and three rural). A total of 1588 patients aged 45-64 years were randomized to one of four intervention groups. In the first group patients were posted a Haemoccult test (Kline Beckman) kit. This group was not invited for a health check. In the second group patients were posted the Haemoccult test kit, together with an invitation to attend for a health check. In the third group patients were posted an invitation for a health check, which explained that the patient would be offered the Haemoccult test kit by the nurse at the health check. In the fourth group patients were just invited for a health check. It was found that combining faecal occult blood testing with the health check did not reduce attendance at the health check--43.5% of patients attended when the Haemoccult test kit was offered by the nurse at the health check, 43.6% attended when a test kit was included with the invitation to attend the health check and 42.9% attended when the health check invitation was posted on its own. Overall, compliance with Haemoccult testing was not significantly increased by associating it with a health check (26.2% versus 25.5%) but compliance was higher when the faecal occult blood testing kit was enclosed with the health check invitation than when it was offered at the health check (31.7% versus 20.6%, P less than 0.001). It is easier and cheaper to combine various screening procedures. Although the overall use of the Haemoccult test in the study population was low, there is no reason why the relatively higher compliance rate obtained on posting the test kit with a health check invitation cannot be achieved in previously unscreened populations with higher expected compliance rates. However, faecal occult blood screening for colorectal cancer should not be undertaken on a population basis until its effectiveness in reducing mortality has been proven by randomized trial. PMID- 1586527 TI - Who will be 'caring for people'? PMID- 1586528 TI - General practitioners' confidence in diagnosing and managing eye conditions: a survey in south Devon. AB - In order to open dialogue aimed at increasing eye care in general practice and reduce waiting times for ophthalmic outpatient appointments general practitioners in the Torbay health district were asked about their levels of confidence in ophthalmology as a subject, and in the diagnosis and management of specific eye conditions. They were also asked about ophthalmic equipment available to them, their management policies for 34 specific eye conditions, and their perceived need for further training in this subject. A total of 75% of the general practitioners responded to the questionnaire. Despite more than half of the general practitioners indicating that they did not feel confident with ophthalmology generally, most expressed confidence in diagnosing and managing common eye conditions. Basic equipment for examining the eye was available to most doctors. Referral policies varied considerably, and these have resource implications. Seventy eight per cent of respondents were prepared to take on more eye care in general practice, and over 80% of general practitioners requested informal teaching sessions in ophthalmology. Support must be forthcoming if general practitioners are to provide eye care in general practice. PMID- 1586529 TI - Family therapy in general practice: views of referrers and clients. AB - Family therapy is being used in a variety of settings, including general practice. To assess the views as to the effectiveness and acceptability of a family therapy clinic in a north London surgery, questionnaires were given to general practitioners referring patients, and to clients. Replies were received from seven doctors and 20 clients, representing 11 families. There was a high level of satisfaction among general practitioners referring patients. The clinic proved to be highly acceptable for clients, with 90% agreeing that it was easier to attend a clinic at the practice than at a hospital; and only one patient thought that knowing the general practitioner worked in the practice made it harder to talk openly. Eighty per cent of patients felt the problem had improved at the time of follow up. Where the problem had not improved, 60% felt that they were dealing with it better. Almost all of the patients felt that the family therapy clinic should become a permanent part of local services. The family therapy clinic in general practice has been shown to be effective and popular with users of the service. PMID- 1586530 TI - History of the Royal College of General Practitioners--the first 40 years. AB - A steering committee met in 1952 to plan for the formation of a new college of general practitioners. An analysis of the work of the Royal College of General Practitioners over its first 40 years suggests that the published aims of the steering committee were largely fulfilled and in some ways exceeded. The unifying theme of the College's development appears to have been the wish to establish general medical practice as a scientific discipline. PMID- 1586531 TI - Controlling your vocabulary. PMID- 1586532 TI - Screening out non-infected urine samples. PMID- 1586533 TI - Future of general practice. PMID- 1586534 TI - Care of long-term mentally ill people. PMID- 1586535 TI - Spirituality, healing and medicine. PMID- 1586536 TI - Spirituality, healing and medicine. PMID- 1586537 TI - Spirituality, healing and medicine. PMID- 1586538 TI - Spirituality, healing and medicine. PMID- 1586539 TI - Chronic fatigue syndrome. PMID- 1586540 TI - Patient satisfaction and style of practice. PMID- 1586541 TI - Reflotron measurement of blood cholesterol. PMID- 1586542 TI - Reaccreditation of GPs. PMID- 1586543 TI - Appliance for hemiplegic patients. PMID- 1586544 TI - Audit in general practice. PMID- 1586545 TI - Knowledge of drug costs: a comparison of general practitioners in Scotland and England. AB - The implementation of drug budgets will make it essential that general practitioners are aware of prescribing costs. A previous study of general practitioners in Scotland found that their knowledge of drug costs was often inaccurate. At the time of the Scottish study, doctors received very limited information on prescribing costs. By contrast, general practitioners in England have been receiving much more detailed information on their prescribing costs since the introduction of PACT (prescribing analyses and cost) in 1988/89. This study examines whether, as a result, doctors in England are more aware of drug costs. The results suggest that they are not; indeed, doctors in Scotland had marginally better knowledge of drug costs. There is a continuing need to improve the cost information available to general practitioners. PMID- 1586546 TI - Antibacterial agents and urinary tract infection: a paradox. PMID- 1586547 TI - Do therapeutic interventions stand the test of time? PMID- 1586548 TI - Relationship between the working styles of general practitioners and the health status of their patients. AB - The aim of this study was to relate the working style of general practitioners to the health status of a sample of their patients. From a large regional sick fund forming part of the national health insurance system in the Netherlands a stratified sample was taken of general practitioners with at least 1000 patients on their list, taking into account the degree or urbanization of the area in which they practised and their annual referral rates to specialists. These 75 general practitioners were observed for two days in their surgeries by trained doctors and rated according to criteria defined beforehand. Taking into account these ratings and the annual figures from the sick fund for prescribing selected drugs and referrals to specialists, the general practitioners were classified into styles of practice - integrated, interventionist or minimal diagnostic. Twenty randomly selected women, aged 50-65 years, from each general practitioner's list, were interviewed and examined by independent doctors. The patients of general practitioners with the integrated practice style appeared to feel more healthy and to have more realistic expectations about the possibilities of professional help for common ailments. They tended to visit their doctor less frequently and to have fewer symptoms. The results showed an association between the quality of general practitioners and patients' health, and it may therefore be concluded that good general practitioners can further the health and well being of their patients. PMID- 1586549 TI - Patients with suspected myocardial infarction: effect of mode of referral on admission time to a coronary care unit. AB - The aim of this prospective study was to determine the delay between the onset of symptoms and arrival in the coronary care unit of patients with suspected acute myocardial infarction, and the relative contribution to the total delay of patient delay, method of referral (self referral or general practitioner referral) and delay in the hospital before reaching the coronary care unit. All patients admitted with chest pain to the coronary care unit at Dudley Road Hospital, Birmingham, over the six month period April-September 1989 were included in the study. Ninety five patients were referred by their general practitioner and 107 patients attended the accident and emergency department directly or arrived by ambulance without contacting their general practitioner. The proportion of self referred and general practitioner referred patients with acute myocardial infarction, angina and non-cardiac chest pain were not significantly different. The total delay was significantly longer for patients who had been referred by their general practitioner (median 5.3 hours) than for self referrals (3.2 hours, P less than 0.001), with a significantly higher proportion of self referrals arriving at the coronary care unit within six hours of the onset of symptoms (77% versus 54%, P less than 0.01). Among general practitioner referrals, initial patient delay accounted for a median of 2.5 hours and the general practitioner's response time for a median of 1.1 hours. The delay in hospital was similar for both groups of patients. In inner city areas, self referral may result in considerably less delay than general practitioner referral allowing a greater proportion of patients to receive effective thrombolytic therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586550 TI - Prevalence of lower extremity arterial disease among elderly people in the community. AB - To estimate the prevalence of lower extremity arterial disease, all patients aged over 65 years registered with a rural general practice near Cambridge were invited to attend for examination of the circulation to the lower extremities; 265 subjects (80%) accepted. Three methods were used to investigate the presence of lower extremity arterial disease - enquiring about symptoms of intermittent claudication; clinical examination (and particularly the detection of arterial bruits); and pressure index calculations from measurements of the ankle and brachial systolic blood pressure using a Doppler ultrasound probe. When examining the legs, the presence of a bruit was taken as stronger evidence of disease than inability to palpate the pulses which may be difficult or impossible to detect for a number of reasons. Forty seven of the 264 patients examined (18%) showed evidence of lower extremity arterial disease. Seven patients showed unequivocal evidence of lower extremity arterial disease as demonstrated by all three criteria, 12 by two criteria and 28 patients on one criterion alone. While the pressure index followed a normal distribution curve, there was a tendency for it to decline with age. Other risk factors which showed a correlation with evidence of disease including current, but not previous, cigarette smoking, and a history of stroke. The significance of the findings is discussed in the context of some degree of arterial pathology in many British subjects in this age group. PMID- 1586551 TI - Self-reported health care over the past 10 years: a survey of general practitioners. AB - To investigate how and where doctors receive their health care, 275 general practitioners were given a questionnaire about their health care in the previous 10 years; responses were received from 247 doctors (90%). Thirty nine per cent of the subjects were registered with a general practitioner who was independent of them. All but one of the remainder were registered with a practice partner, close friend or relative. Whatever the relationship of the subjects with their own general practitioner, personal health problems were managed to a great extent by themselves. Most (84%) of the medication taken in the previous five years had been self-prescribed and one third of medical investigations had been self initiated. Over half of the general practitioners studied had seen a specialist about their health in the preceding 10 years; 51% had referred themselves. A 'jury' of seven general practitioners compared the subjects' referrals to a specialist with the care that would be expected for a non-general practitioner patient. Where the jury reached agreement, 68% of referrals were thought to have been appropriate; self-referrals were significantly more likely to be thought inappropriate (P less than 0.05); and self-treatment prior to self-referral to a specialist was considered inappropriate in 78% of cases. The amount of self prescribed medication and frequency of consultation was the same, whatever relationship the subject held with the general practitioner. This study shows that most general practitioners manage their own health care. The question of whether this is always appropriate is raised and the provision of an occupational health service for general practitioners is discussed. PMID- 1586552 TI - Characteristics of general practitioners who are high attenders at educational meetings. AB - The characteristics of general practitioners in the west of Scotland who are high attenders at meetings accredited for the postgraduate education allowance were studied. One hundred and seventy one principals in general practice (9.5%) had attended more than 35 half-day sessions of accredited education between 1 April 1989 and 31 December 1990 and 34 doctors (1.9%) had attended more than 45 half day sessions. The highest percentage of the doctors worked in Greater Glasgow and Lanarkshire. The doctors who were high attenders were relatively more likely to be women, to be members of the Royal College of General Practitioners and to work in a training practice. The majority of the doctors had been qualified for between 10 and 30 years and worked in group practices of three or more doctors. The characteristics of high attenders contrast markedly to doctors who are low attenders. That there were such a large number of high attenders at educational meetings is encouraging. PMID- 1586553 TI - False contraindications to childhood immunization. AB - An immunization advisory clinic was set up in mid-Essex in 1988 to provide a referral facility for professionals and parents who were unsure about the eligibility of certain children to receive immunization. This paper describes four typical cases. The history and management of each case are described and the fact that all the children were successfully immunized is highlighted. It is hoped that by sharing the experiences of the immunization advisory clinic with other professional staff, more positive decisions regarding immunizations will be made. PMID- 1586554 TI - 'Will you help me with my research?' Gaining access to primary care settings and subjects. AB - This paper is concerned with the negotiation of agreement to carry out research in primary care settings. It is argued that this is a key part of any research project, and that careful handling of this process will not only improve response rates, but will also often enhance the quality of the data obtained. A number of strategies for negotiating access are proposed which have been developed and applied in primary care settings. These strategies depend on creating a sense of collective ownership of projects between researchers and participants which contributes to the successful completion of the projects and provides a positive atmosphere for further collaboration. PMID- 1586555 TI - Forty years of the RCGP: a view from outside the British Isles. PMID- 1586556 TI - Peak flow meters. PMID- 1586557 TI - Triple therapy against Helicobacter pylori. PMID- 1586558 TI - Consulting habits of temporary residents. PMID- 1586559 TI - GPs and optometrists. PMID- 1586560 TI - Management of URTIs. PMID- 1586561 TI - Clinic for the prevention of osteoporosis. PMID- 1586562 TI - Trainees' knowledge of AIDS and HIV. PMID- 1586563 TI - Vocational training. PMID- 1586564 TI - Confiding relationships in elderly people. PMID- 1586565 TI - Private health care in the USA. PMID- 1586566 TI - Travelling for earlier surgical treatment. PMID- 1586567 TI - Calcitonin gene-related peptide (CGRP)-immunoreactive nerve terminals in the whole mount preparations of the dog urethra. AB - To visualize the entire shape of the intraepithelial nerve fibers, whole mount preparations of the dog urethra were produced and immunostained with an antiserum against CGRP, one of the predominant substances contained in the nerves. The immunoreactive nerves in the lamina propria were smooth (non-beaded) in appearance and weak in immunoreaction. Within the epithelium, they displayed typical beaded profiles and were intense in immunoreaction. The intraepithelial fibers branched and wound into an extensive network with wide meshes ("reticular terminal"). The bead-like swellings included large ones resembling Herring bodies in hypophyseal neurosecretory fibers. Another type of nerve terminal, consisting of fine and weakly immunopositive fibers, was also found in the epithelium. These branched in dendritic or in dense bouquet-like fashion, occupying smaller areas ("bouquet-like terminals). Vesicular swellings often characterized these terminals, though they were smaller and more uniform in size and far less in their amount of immunoreactive substance than were the swellings in the reticular terminals. Both types of nerve terminals originated from the same nerve trunk. The connection between the reticular and bouquet-like terminals, which may presumably represent secretory and receptive parts, respectively, morphologically supports the possible occurrence of an axon reflex in the urethral CGRP neurons. Our whole mount preparations, when doubly stained with CGRP and serotonin antibodies, further revealed the CGRP-positive reticular terminals being closely associated with serotonin- or CGRP-immunoreactive paraneurons dispersed in the epithelium. PMID- 1586569 TI - Innervation of the periodontal ligament in the dog with special reference to the morphology of Ruffini endings. AB - The distribution and terminal formation of nerves in the periodontal ligament of dog incisors and canines were investigated by immunohistochemistry for neurofilament protein (NFP) and by electron microscopy. The NFP-immunoreactive nerve fibers were found to be densely distributed in the apical third of the periodontal ligament, while they were sparse in the coronal two thirds. Most of the nerve endings in the periodontal ligament showed a tree-like appearance and resembled those nerve endings demonstrated in the periodontal ligament of human and monkey under the category of free nerve endings. Presumable axon terminals of these were slightly thicker than preterminal portions, running along periodontal collagen fibers and tapering within them. In light microscopic images, at least, they differed from the Ruffini endings which are commonly seen in rodents, displaying a glove-like configuration with extremely expanded tips. Under the electron microscope, however, the tree-like endings of the dog appeared similar to the Ruffini endings of rodents: their terminals were filled with mitochondria, covered with a cytoplasmic process of a Schwann cell, and surrounded by collagen fibers. These ultrastructural findings, combined with the results of previous physiological studies suggest that the nerve endings demonstrated in the present study can be identified as Ruffini endings. It is even stressed that the dog-type of Ruffini ending can be regarded as a representative of the sensory receptors in the mammalian periodontal ligament. In addition to these endings, knobbed endings, corpuscular (lamellated and glomerular) endings, and free nerve endings were rarely encountered in the periodontal ligament of incisors and canines of the dog. PMID- 1586568 TI - Immunohistochemical studies on the localization of aromatase and 17 alpha hydroxylase/C17-20 lyase (17 alpha-lyase) in estrous cycling and pregnant hamster ovaries. AB - In order to clarify periodic changes in the localization of enzymes engaged in estrogen biosynthesis during the estrous cycle, immunohistochemical and fine structural studies were performed using estrous cycling and pregnant hamster ovaries. Results showed that ovulation takes place at midnight between Day 4 and Day 1 in the regular 4 day-cycle hamster. Immunoreactivity for aromatase is localized in the granulosa cells of the secondary follicle and granulosa lutein cells during the morning (10:00 am) of Day 1 to the evening (5:00 pm) of Day 4; in the night (9:00 pm) of Day 4, only the granulosa cells of the Graafian follicle showed a strong immunoreaction. As for 17 alpha-lyase, theca interna cells of the secondary follicle are immunopositive throughout Day 2 to the morning (10:00 am) of Day 4. Only a few cells in the theca interna of the Graafian follicles are immunopositive in the evening (5:00 pm) of Day 4. No positive cells for this enzyme were detected in the night (9:00 pm) of Day 4 or morning (10:00 am) of Day 1. The rapid decrease of estrogen biosynthesis occurring just before ovulation is considered to be due to the disappearance of 17 alpha-lyase in the theca interna cells of the ovary. On Day 10 of pregnancy, the granulosa cells of the secondary follicles and both the granulosa and theca lutein cells of the corpora lutea are immunostained with the aromatase antibody, while the theca interna cells of the secondary follicles reacted positively to the 17 alpha-lyase antibody. Only the granulosa and theca interna cells from the large preovulatory Graafian follicle of Day 4 (proestrus) which are positively stained for aromatase as well as 17 alpha-lyase show ultrastructural features typical of steroid secretory cells. PMID- 1586570 TI - Calcification preceding new bone formation induced by demineralized bone matrix gelatin. AB - Demineralized bone matrix gelatin (BMG) was implanted into the skeletal muscle of Sprague-Dawley (S.D.) rats, and histological changes were examined 3, 5, 7, 10 and 15 days later. Before bone formation, a specific calcification process was found in most of the BMG from day 5 and 7 after implantation. The heterotopic calcified sites were not always consistent with the sites of the alkaline phosphatase activity. It was considered that this calcification progresses without any cellular components, and we distinguished this type of calcification as "acellular mineral deposition" from the calcification which occurs in new bone formation. This "acellular mineral deposition" was first observed as small spherical calcified deposits in the BMG on day 7 after implantation; these deposits then gradually grew and fused with each other. Some multinucleated cells appeared near the site of calcification on day 7 after implantation, but osteoblasts or osteoblast-like cells were scarcely observed around the calcified deposits in BMG until day 7. Vascularization was often observed near the "acellular mineral deposition" and the new bone formation. Fourier transform infrared spectroscopy showed that the calcified deposits in BMG were composed of hydroxyapatite, carbonateapatite and other calcium phosphate components, and that the first two components became prominent with time. It is believed that the "acellular mineral deposition" is due to the deposition of calcium and phosphate into the BMG by a process of heterogenic nucleation that does not involve osteoblasts or matrix vesicles. Bone formation induced by the BMG occurred after the "acellular mineral deposition." The experimental calcification shown in this paper seems a useful model for the study of biocalcification. PMID- 1586571 TI - Cytoskeletal architecture of the matrix cell and neuroblast in the neural tube of the chick embryo. AB - Cytoskeletal architecture of the matrix cell and neuroblast in the wall of midbrain of 4-6 day-old chick embryos was examined by electron microscopy and immunohistochemistry. The matrix cell, the undifferentiated stem cell later producing neurons and glial cells in the central nervous system, is characterized ultrastructurally by abundant free ribosomes and a poorly developed cytomembrane system. A few microtubules running in random directions are observed in the matrix cell body. In the cell processes, microtubules are oriented longitudinally, and linked with each other by cross-bridges, presumably composed of microtubule-associated proteins (MAPs). The cell processes contain abundant cytoplasmic filaments including a large amount of actin filaments which adhere to the plasma membrane of junctional complexes located immediately below the inner surface of the neural tube. In the neuroblast which has been differentiated from the matrix cell, the cytomembranous organelles, especially rough endoplasmic reticulum are markedly better developed than in the matrix cell; microtubules are more numerous in the cell body. The cell process contains many microtubules with cross-bridges and a few intermediate filaments, which are relatively characteristic of the cytoskeleton of the neuroblast. Phalloidin-staining and immunohistochemistry showed that the neuroblast was richer in F-actin, beta tubulin, MAP1, MAP2, tau, calspectin, and synapsin I than the matrix cell. As the matrix cell differentiates into the neuroblast, both the cytoskeletal and cytomembranous systems proved to develop features, characteristic of a neuron. PMID- 1586572 TI - Effects of 5-hydroxydopamine and 6-hydroxydopamine on the ultrastructure of type I cells in paraganglia of the rat recurrent laryngeal nerve. AB - The ultrastructure of the Type I cells in paraganglia of rat recurrent laryngeal nerve (RLN) was studied after the administration of 5-hydroxydopamine (5-OHDA) and 6-hydroxydopamine (6-OHDA). Normal Type I cells of RLN-paraganglia contained abundant organelles and their cytoplasm was characterized by the presence of numerous membrane-bounded dense-cored vesicles (DCVs). The DCVs were round in profile (diameter 107.67 +/- 0.06 nm, all values expressed as mean +/- s.e.m. in the present study) and possessed dense cores of moderate to low electron density. After 5-OHDA treatment (single injection, 100 mg/kg b.w., i.v.), the majority of DCVs were filled with a material of high electron density. No significant difference was observed between the profile diameter of the DCVs in 5-OHDA treated rats (104.96 +/- 0.06 nm) and that in normal rats. After 6-OHDA treatment (three injections, 100 mg/kg b.w. each at 12 h intervals i.p.), no significant alteration in the electron density of the core was noted. However, most of the DCVs were enlarged and round, elliptical or irregular in profile (190.57 +/- 2.77 nm x 130.34 +/- 2.09 nm). The dense core of DCVs was centrally or eccentrically located in DCVs. The results of the present study indicate that: 1) there is only one type of granulated glomus cell (i.e., Type I cells) in the rat RLN paraganglia under normal physiological condition; and 2) since the ultrastructural morphology of DCVs in Type I cells of rat RLN-paraganglia is altered after 5-OHDA or 6-OHDA treatment, these cells may possess mechanisms for the uptake of false adrenergic neurotransmitter and/or neurotoxin. PMID- 1586573 TI - Lymphocyte subpopulations in mediastinal milky spots of mice: light- and electron microscopic immunohistochemical observations. AB - The structure and distribution of cellular components in the mediastinal milky spots of C57BL/6 mice were studied by electron microscopy and immunohistochemistry. The mediastinal milky spots were generally covered with plump mesothelial cells with hemidesmosome-like structures in small projections of the cytoplasm, and consisted mainly of clusters of lymphocytes, macrophages and fibroblasts. Macrophages and lymphocytes were often seen passing between mesothelial cells and migrating into the pleural cavity. Neither high endothelial venules (HEV) nor lymphatics were present in the mediastinal milky spots. Thy 1(CD5)-, L3/T4(CD4)- and Lyt-2(CD8)-positive cells were located predominantly at the basal area adjacent to fat cells under the lymphoid tissue. IgG- and Ia positive cells dominated throughout the lymphoid tissue, whereas IgM-positive cells were observed in the lymphoid tissue other than the basal area. Mediastinal milky spots showed a specific distribution of lymphocyte subsets: the T cell area comprised the basal area, and the B cell area was mainly other areas. The mean percentages of CD4-, CD8-, IgM-, IgG- and IgA-positive cells in the mediastinal milky spots were 16.5%, 20.1%, 28.8%, 37.3% and 2.1%, respectively; the percentage of B cells was higher than that of T cells. IgG- and IgM-positive cells were the main lymphocyte subsets in the mediastinal milky spots. The most characteristic finding was that IgA-positive cells were a very minor cellular component. PMID- 1586574 TI - Enhanced osteoinduction by intramuscular grafting of BMP-beta-TCP compound pellets into murine models. AB - The osteoinductive effects of bone morphogenetic protein (BMP, derived from murine osteosarcoma) were studied with regard to its use combined with beta tricalcium phosphate (beta-TCP). BMP and beta-TCP were molded into pellets by the "pressure method", originated by us and transplanted to ddY mice. Control mice received interdorsal muscular implantations of either the BMP or beta-TCP pellets. The animals were sacrificed 1, 2 and 3 weeks after grafting, for radiological, histochemical, and ultrastructural observations. The BMP-beta-TCP compound pellets induced faster cartilage and bone formation, whereas these activities were slower when pellets made solely of BMP were used. The beta-TCP pellets demonstrated no osteoinductive properties. Observations revealed two types of beta-TCP resorbing multinuclear giant cells. One was osteoclastic, expressing calcitonin receptors, having numerous mitochondria and ruffled border like structures; the other was not osteoclastic in nature. In animals grafted with the compound pellets, a great number of osteoclastic cells gathered on the pellets, much earlier than those grafted with the pellets made of BMP alone. Then, osteoblastic bone formation over the cement lines followed an osteoclastic resorption of both beta-TCP and newly formed bone. In contrast, BMP induced few osteoclastic cells, resulting in slower bone coupling. Furthermore, the faster bone formation induced by the compound pellets seemed to be associated with the presence of beta-TCP. Porous by nature, beta-TCP would entrap BMP within its micropores, and thus, the intrinsically diffusible BMP is retained and its action consequently prolonged. In addition, the compound pellet offered increased surface contact between BMP and mesenchymal cells. Therefore, BMP-beta-TCP compound pellets induce cartilage and bone formation more rapidly than does BMP alone. PMID- 1586575 TI - Computed tomography in traumatology with special regard to the advances of three dimensional display. AB - There is a variety of methods to aid in the diagnosis of fractures requiring operative treatment. A computer program that produces pseudo-three-dimensional (3D) images from sets of axial computed tomograms is used for examining fractures in areas of complex skeletal anatomy. The resulting reconstructions, representing the surface in a form similar to that of anatomic preparations, can facilitate the process of diagnosis. They are also valuable for planning operations. The 3D information can be used to define the size, shape, and location of the various fracture types. We have used the technique in more than 500 patients with injuries to the skull, spine, acetabulum, sternoclavicular joint, shoulder, knee, and calcaneus and are able to demonstrate the benefit of special investigation protocols. PMID- 1586576 TI - Three- to five-year results with the cementless Harris-Galante acetabular component used in hybrid total hip arthroplasty. AB - In this paper we present our 3- to 5-year results after hybrid total hip replacement using the cementless porous coated Harris-Galante acetabular component and the cemented Griss femoral component in 39 patients with 40 implantations. Postoperatively, mild to moderate pain was experienced by 16.1% of patients, mostly following hard activity. A slight to moderate limp occurred in 24.2%. All patients were able to walk more than 1000 m. Full-time use of support was required by 2.8%. The postoperative range of motion was increased in 93.9%. Radiographically, none of the acetabular or femoral components had to be classified as unstable. Only one acetabular component displayed complete (i.e., along all interface zones) radiolucency and was therefore classified as possibly unstable. PMID- 1586577 TI - The influence of metal backing in unicompartmental tibial component fixation. An in vivo roentgen stereophotogrammetric analysis of micromotion. AB - The fixation of the tibial component in 36 patients with conventionally cemented unicompartmental knee arthroplasties for femorotibial gonarthrosis was studied using roentgen stereophotogrammetric analysis (RSA). Twenty-four tibial components were all-polyethylene while 12 were metal-backed. The follow-up was for 6 years. Significant migration was detected for all cases but two and ranged from 0.3 mm to 5.4 mm. The greater part of the migration occurred during the first 1-2 years, after which two-thirds of the prostheses remained stable. Seven all-polyethylene components were subjected to a stress examination after 1-2 years and displacement, induced by external forces, was found in all seven. A strong correlation was found between the extension of the radiolucent line and the migration. Otherwise, neither demographic, clinical, nor radiographic data correlated with the RSA results. In this study metal backing did not have any influence on prosthetic fixation as measured by RSA. PMID- 1586578 TI - A simpler surgical technique to treat aseptic nonunion-associated femoral length discrepancy. AB - In a prospective study from December 1986 to August 1989, 17 consecutive patients with femoral shortening due to aseptic nonunion of femoral shaft fractures were treated with limitedly open Gross-Kempf locking nailing with a lengthening procedure. Patients were followed up for at least 1 year (average 25 months). There was a 88.2% union rate with an average union period of 5.2 months. Average lengthening was 2.4 cm (1.0 approximately 3.0 cm), and average operation time 90 min (70 approximately 130 min). The blood loss was slight (average 200 ml). Complications (11.8%) were 5.9% implant failure and 5.9% nonunion which were not difficult to manage. No neurovascular complications were noted. We conclude that for 5 cm shortening or less in femoral aseptic nonunion, this treatment constitutes the simplest technique and can achieve a very satisfactory result. PMID- 1586579 TI - External fixation of the distal end of the radius: the same technique for different patient populations? AB - A series of 56 consecutive patients with 59 fractures of the distal end of the radius, treated with a unilateral Hoffmann external fixator between 1980 and 1988, is presented. Forty-seven of these patients underwent clinical re examination at home. We could distinguish two different groups of patients: an older female group with an average age of 59.2 years and a younger male group with an average age of 40.1 years. The fractures in the women were caused by lower energy trauma than those in the men (P less than 0.05). The men had significantly more complex fractures (Frykman type VII or VIII) than the women (P less than 0.05). The indications for external fixation were significantly different in men and in women (P less than 0.01). The external fixator remained in place for an average of 5.7 weeks. The injured wrist had on average 71% of the strength of the contralateral wrist. Eighty-seven percent of the patients had no complaints in performing their daily activities. In 70% X-ray showed anatomical reduction, in 64% there was an excellent cosmetic result and in 68% the functional end results were excellent or good. Functional end results can be ameliorated by paying more attention to anatomical reconstruction of the wrist joint. It may be necessary to supplement the external fixation with open reconstruction of the wrist joint and/or a cancellous bone transplant. In some cases, a change of procedure to plate osteosynthesis could be the treatment of choice. PMID- 1586580 TI - No physiologic age-related increase of circulating somatomedin-C during early stage of Perthes' disease: a longitudinal study in 21 boys. AB - Perthes' disease was originally viewed as a local ischaemic necrosis of the femoral head. Several authors, however, have presented data suggesting that children with this disease also suffer from a general disorder of skeletal maturation. Hormonal changes in the hypothalamus-pituitary-growth plate axis have been discussed as a possible underlying cause and contradictory results reported on the role of the somatomedins in this process. In this report for the first time sequential data are presented on plasma somatomedin-C (Sm-C/insulin-like growth factor I) levels in 21 boys with Perthes' disease. Values were compared with data from 105 control subjects. The physiologic increase with age of plasma Sm-C levels in the control group was either absent or diminished in children with early-stage Perthes' disease (P less than 10(-6), signs test). The Sm-C values in affected children were low. Our data correlate well with reports from others of retarded skeletal maturation in children with Perthes' disease and support the hypothesis of an accompanying disorder of the synthesis or release of Sm-C/IGF-I or its binding proteins. PMID- 1586581 TI - Aseptic osteonecrosis of acetabulum following prosthetic replacement of the femoral head. A case report. AB - Acetabular osteonecrosis is a rare condition. Only five cases with histological analysis have been reported in the literature, and these patients had previously received radiotherapy. The 67-year-old woman reported on here, who had had no major systemic disorder or local radiotherapy, and who had never consumed alcohol, developed aseptic osteonecrosis of the acetabulum after femoral head replacement with a cemented Austin-Moore prosthesis for aseptic osteonecrosis of the femoral head following femoral neck fracture. The necrosis was found during surgery to go so deeply into each bone composing the acetabulum that the hip joint could not be revised, and we had to perform a Girdlestone resection arthroplasty. The radiographic and histological findings resembled those reported in cases of aseptic osteonecrosis of the acetabulum after radiotherapy. PMID- 1586582 TI - Postoperative osteomyelitis due to Mycobacterium fortuitum. A case report. AB - A rare case of osteomyelitis of the tibia caused by Mycobacterium fortuitum which developed after closed intramedullary Kuntscher nail fixation is reported. After extraction of the nail, combination therapy with antituberculous drugs, ofloxacin, and interleukin 2 was undertaken and bony union was achieved. Since a bone cyst formed during union, curettage and conventional cancellous bone grafting were performed. The patient is now pain-free even with prolonged weight bearing. The success of treatment in this case is in contrast to other reports of the disease. PMID- 1586583 TI - Idiopathic acro-osteolysis in an elderly woman. A 10-year follow-up. AB - We report a case of idiopathic acro-osteolysis in an 80-year-old, otherwise normal woman. The patient first presented at the age of 70 years with a 3-year history of progressive shortening of the left toes. There was no history of trauma or bone disorders. She had osteolysis of the left second to fourth distal phalanges. Angiography was normal. During follow-up over 10 years the osteolysis gradually progressed and spread to affect the right toes. PMID- 1586584 TI - The effect of the enantiomers of ibuprofen and flurbiprofen on the beta-oxidation of palmitate in the rat. AB - The effects of the enantiomers of ibuprofen (0.25 and 0.50 mmol/kg b.w.) and flurbiprofen (0.01, 0.03, and 0.06 mmol/kg b.w.) on the beta-oxidation of palmitate were investigated in the rat. The mean cumulative exhalation of 14CO2 after ip administration of [U-14C]palmitic acid was significantly reduced over 6 h by ibuprofen at the higher dose but not at the lower dose for either enantiomer. There was no difference between the enantiomers, the reduction over 6 h being 31.3 and 33.0% for (R)- and (S)-ibuprofen, respectively. There was also a significant inhibition of beta-oxidation by flurbiprofen at all 3 doses. Again, there was no stereoselectivity evident in this inhibition. Flurbiprofen was much more potent than ibuprofen in eliciting this effect, the 0.01mmol/kg dose giving a similar reduction in beta-oxidation as observed for the 0.50 mmol/kg dose of ibuprofen. The data support the hypothesis that inhibition of the in vivo beta oxidation of palmitate by ibuprofen and flurbiprofen is primarily via a nonstereoselective noncoenzyme A-dependent mechanism. PMID- 1586585 TI - Stereoselective disposition and tissue distribution of carvedilol enantiomers in rats. AB - After intravenous bolus injection of rac-carvedilol at 2 mg/kg to the rat, the (+)-(R)- and (-)-(S)-enantiomer levels in the blood and tissues (liver, kidney, heart, muscle, spleen, and aorta) were measured by stereospecific HPLC assay. As compared with the (+)-(R), the (-)-(S) had a larger Vdss (3.32 vs. 2.21 liter/kg), MRT (33.4 vs. 25.6 min), and CLtot (96.1 vs. 83.8 ml/min/kg). AUC comparison after iv and po administration showed systemic bioavailability of the (-)-(S) to be about half that of its antipode, explained by the fact that the free fraction of the (-)-(S) in blood was 1.65-fold greater than that of the (+) (R). Tissue-to-blood partition coefficient values for the (-)-(S) were 1.6- to 2.1-fold greater than those for the (+)-(R) in all tissues, showing that the (-) (S) accumulates more extensively in the tissues. These results were consistent with the greater Vdss for the (-)-(S) estimated from systemic blood data. The stereoselective tissue distribution of carvedilol enantiomers results from an enantiomeric difference in plasma protein binding rather than in tissue binding. PMID- 1586586 TI - The resolution, isolation, and pharmacological characterization of the enantiomers of a benzamide containing a chiral sulfoxide. AB - Rac-ML-1035 (MDL 201,035: 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N-[2 (diethylamino)ethyl] benzamide hydrochloride) is a racemic gastroprokinetic with serotonergic (5-hydroxytryptamine, 5-HT) activity and a novel chiral sulfoxide substituent. Chromatographic and chemical methods have been developed to resolve the enantiomers of rac-ML-1035, and the absolute configuration of the (R) enantiomer has been determined. We also report pharmacological characterization of rac-ML-1035 and its respective isomers. Radioligand binding to rat cortical membranes revealed that (R)-ML-1035 (MDL 201,226) and (S)-ML-1035 (MDL 201,227) had equivalent activity at the 5-HT3 receptor. However, in isolated tissue studies including field-stimulated guinea pig ileum, field-stimulated rat fundic strip, and nonstimulated guinea pig ileum, (S)-ML-1035 was equally potent yet had greater maximal activity than (R)-ML-1035 in eliciting or facilitating cholinergic contractions. Thus, enantiomers of rac-ML-1035 can be resolved, and the relative configuration of these isomers influences their pharmacological activity. PMID- 1586587 TI - Enantio- and regioselectivity in the epoxide-hydrolase-catalyzed ring opening of simple aliphatic oxiranes: Part I: Monoalkylsubstituted oxiranes. AB - The in vitro conversion of chiral aliphatic monoalkylsubstituted oxiranes into 1,2-diols catalyzed by epoxide hydrolase of rat liver microsomes occurs with substrate enantioselectivity and regioselectivity. Substrate enantioselectivity is generally low, and has the same sense, for methyloxirane, vinyloxirane, epichloro-, and epibromohydrin. In the hydrolysis of t-butyloxirane inhibitory effects are involved leading to a complex pattern of enantioselectivity. All investigated monosubstituted aliphatic oxiranes are hydrolyzed with high regioselectivity by nucleophilic attack of water at the unsubstituted ring carbon atom. The enantiomeric excess of the unreacted oxirane substrates and the diol metabolites formed were determined by complexation and inclusion gas chromatography. PMID- 1586588 TI - Enantio- and regioselectivity in the epoxide-hydrolase-catalyzed ring opening of aliphatic oxiranes: Part II: Dialkyl- and trialkylsubstituted oxiranes. AB - The extent of substrate enantioselectivity and regioselectivity of a series of aliphatic 2,3-dialkyl- and trialkylsubstituted oxiranes in their in vitro epoxide hydrolase-catalyzed hydrolysis depends on the size of the alkyl residues and on the substitution pattern of the oxirane ring. The enzyme-catalyzed hydrolysis of cis-oxiranes, containing at least one methyl substituent, shows complete or nearly complete substrate enantioselectivity and regioselectivity with nucleophilic attack by water occurring with inversion of configuration at the methylsubstituted ring carbon atom of (S)-configuration. In the hydrolysis of the isomeric trans-oxiranes, both enantiomers are metabolized with a higher rate for the (2S;3S)-enantiomer. The conversion of trimethyloxirane occurs with high substrate enantioselectivity in favor of the (S)-enantiomer and with complete regioselectivity at the monomethylsubstituted ring carbon atom. The differentiation of the enantiotopic ring carbon atoms (product enantioselectivity) in the smallest aliphatic meso-oxirane, cis-2,3 dimethyloxirane, leads to (2R;3R)-butane-2,3-diol with ee = 86%. cis-2-Ethyl-3 propyloxirane, possessing alkyl residues larger than methyl, represents an extremely poor substrate in the epoxide-hydrolase-catalyzed hydrolysis process. PMID- 1586589 TI - Use of a high frequency ultrasound microscope to image the action of 2 nitroimidazoles in multicellular spheroids. AB - A system was designed to allow imaging of control and drug treated multicellular spheroids with a high frequency backscatter ultrasound microscope. It allowed imaging of individual spheroids under good growth conditions. Since little data were available on cellular toxicity of ultrasound at these high frequencies (80 MHz), studies were undertaken to evaluate effects on cell survival, using a colony forming assay. No toxicity was observed on cell monolayers subjected to pulsed ultrasound at the intensities used for imaging experiments. Spheroids were also subjected to pulsed ultrasound and no growth delay was observed when exposed spheroids were compared with mock-exposed spheroids. Imaging studies were performed and pictures of untreated spheroids were obtained in which the necrotic and viable regions are clearly distinguishable. When the hypoxic cell cytotoxin 1 methyl-2-nitroimidazole (INO2) was added to the spheroid, dramatic changes were observed in the backscatter signal. The interior viable cells of the spheroid were selectively affected. Changes in the backscatter signal were also observed when the reduction product 1-methyl-2-nitrosoimidazole (INO) was added to spheroids. With INO however, the changes were located at the periphery of the spheroid, presumably due to the high reactivity of INO which limits diffusion of the drug into the spheroid. The present work demonstrates the potential usefulness of ultrasound backscatter microscopy in following the action of selected drugs in this in vitro tumour model. PMID- 1586590 TI - Sequential alteration of peanut agglutinin binding-glycoprotein expression during progression of murine mammary neoplasia. AB - A sequential, quantitative loss of Peanut agglutinin (PNA) binding with progression of mouse mammary cells from normal to preneoplastic to neoplastic phenotypes was observed. Normal mammary epithelium, preneoplastic mammary lesions designated D2HAN (D2-type hyperplastic alveolar nodules) and a series of nine spontaneous tumours (D2ST1, D2ST2, D2ST3, D2ST4, D2A1, D2F2, D2.0R, D2.1, EMT6R08) derived from mice bearing D2HAN were grown in culture and analysed by flow cytometry with respect to PNA binding intensity to the cell surface. Primary cultures of normal mammary epithelium strongly bound PNA. A stepwise decrease in PNA binding by preneoplastic D2HAN cells and subsequent tumours arising from those hyperplastic lesions was observed. Three cloned tumour subpopulations derived from such tumours exhibited dramatic differences in PNA binding ranging from high (D2.0R) to low (D2.1) to very low (D2A1 cells). Their growth rate in vitro was similar. However, an inverse correlation between PNA binding and malignant characteristics, such as the incidence and latency of subcutaneous tumours and the efficiency of the tumour cells to form lung colonies after i.v. injection, existed. Cells subsequently derived from tumours resulting from injection of the D2.0R clone (high PNA binding, low tumorigenicity) were found to have diminished PNA binding properties and to be more tumorigenic when reimplanted into syngeneic mice. The difference in PNA binding (up to 50-fold) between normal mammary cells and other mouse mammary tumour cells, i.e., unrelated to D2HAN lesions, was also seen. These include six sister subpopulations derived from a single BALB/cfC3H mouse mammary tumour (lines: 67, 66c14, 168FARN, 4TO7, 68H, 64pT) as well as SP1 spontaneous CBA/J mouse mammary carcinoma. The difference was greatly reduced by neuraminidase treatment suggesting a masking of PNA binding sites by sialic acid. Separation of cell lysates by SDS-PAGE revealed a high molecular weight PNA binding glycoprotein (greater than 250 kd) expressed by normal mammary epithelium and preneoplastic D2HAN cells, but not by tumour cells regardless of neuraminidase treatment. A PNA reactive glycoprotein of approximately 90 kd was uniquely expressed in normal mammary epithelial lysates, although neuraminidase treatment exposed a similar band in a few tumour lines. Normal mammary epithelium, preneoplastic D2HAN cells, and the poorly tumorigenic clone D2.0R expressed a PNA binding glycoprotein of approximately 150 kd. This band appeared to be specifically sialylated during transition from the high PNA binding, low tumorigenic phenotype of D2.0R cells to the low PNA binding, highly tumorigenic phenotype of cells isolated from tumours resulting from s.c. implantation of D2.0R cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1586591 TI - Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6. AB - Collagen synthesis in intestinal anastomoses has been measured in rats after in vivo administration of cytostatics. The cytostatics were administered during 5 consecutive days either intravenously or intraperitoneally. On day 3 of the course the rats received both an ileal and a colonic anastomosis. The animals were sacrificed 3 and 7 days after operation. The cytostatics regimen used was a combination of 5-fluorouracil, bleomycin and cisplatinum in a dose of 10, 2 and 0.35 mg kg-1 day-1, respectively. In an additional group, a twice higher dose was given intraperitoneally. Three days after operation a severe inhibition of the collagen synthesis was observed in all the cytostatics treated groups, both in ileum and in colon. The effects of intraperitoneal administration were much more pronounced than those observed after an equal dose given intravenously. Seven days after operation the collagen synthesis in the intravenously treated groups was restored to the level of the control group. However, in the intraperitoneal groups the collagen synthesis in ileal anastomoses was still inhibited. Thus, cytostatics suppress collagen synthesis in intestinal anastomoses. The effect is more severe after intraperitoneal than after intravenous administration, confirming our earlier hypothesis that the former mode of administration comprises a higher risk for anastomotic integrity. PMID- 1586592 TI - Transforming growth factor-beta mRNA expression and growth control of human ovarian carcinoma cells. AB - The pattern of TGF beta expression and in vitro response to TGF beta has been defined in three ovarian carcinoma cell lines (PEO1, PEO4 and PEO14). Marked differences in both mRNA expression and growth responses were detected between the cell lines. All expressed mRNA for TGF beta 3, PEO1 and PEO4 but not PEO14 expressed mRNA for TGF beta 1, whereas PEO14 but not PEO1 and PEO4 expressed TGF beta 2. Growth of PEO14 cells in culture was markedly inhibited by both TGF beta 1 and beta 2. PEO1 cells were inhibited by TGF beta 1, but not TGF beta 2 whilst growth of PEO4 cells were not affected by exposure to either of these peptides. These data indicate that several elements of potential autocrine loops involving TGF beta's are present within ovarian cancer cells. PMID- 1586593 TI - Effects of intraperitoneal recombinant interleukin-1 beta in intraperitoneal human ovarian cancer xenograft models: comparison with the effects of tumour necrosis factor. AB - The effect of intraperitoneal (i.p.) injection of recombinant human interleukin-1 beta (rhIL-1 beta) was studied in three i.p. nude mouse xenograft models of human ovarian cancer (HU, OS, and LA). Intraperitoneal rhIL-1 beta administration led to a dose dependent replacement of peritoneal ascitic tumour with solid tumours attached to the peritoneum and intraabdominal viscera in two (HU and LA) out of the three xenograft models. In the third xenograft model (OS), low doses of rhIL 1 beta (10 ng day) promoted micrometastatic peritoneal implants of tumour, but higher doses of rhIL-1 beta (1 microgram day) had a marked antitumour effect. This was due to direct cytotoxicity for tumour cells and was not related to peritoneal neutrophil influx induced by rhIL-1 beta. Recombinant human TNF (rhTNF) also promoted tumour implantation in all three xenograft models, but its antitumour effects differed from rhIL-1 beta. TNF increased the survival of HU and LA bearing mice, but had no antitumour effect in the OS xenograft model. Analysis of peritoneal fluid and tumour xenografts showed that TNF induced murine IL-1 in the tumour bearing mice. The magnitude of IL-1 induction indicated that TNF induced IL-1 did not contribute significantly to its effects. PMID- 1586594 TI - Patterns of methylation of the c-myc gene in human colorectal cancer progression. AB - Over-expression and abnormal intracellular location of the product of the oncogene c-myc in colonic dysplasia and neoplasia may be related to alterations in epigenetic mechanisms controlling the functioning of this gene. We have investigated the methylation patterns of the c-myc oncogene in human colorectal tissue representing various stages of dysplasia and neoplasia, including metastasis to liver, omentum and lymph node. Comparison of normal and neoplastic tissues from the same patient showed a decrease in methylation in a specific CCGG site in the third exon of c-myc through the progression from normal via dysplastic to neoplastic and metastatic tissue. Quantitative analysis revealed that in colonic adenocarcinomas an average of 66.1% and in metastatic deposits 83.1% of the myc gene DNA was hypomethylated at this site, as compared to a value of 9.2% in normal colonic mucosa. Adenomatous polyps showed an average value of 50.5% and hyperplastic polyps, 24.8%. The results suggest that partial hypomethylation of the c-myc gene third exon is associated with cell proliferation, and that deregulation of proliferation may be linked to the high levels of hypomethylation, presumably involving both copies of the gene in some cells, which occur at a relatively early stage in neoplastic progression. PMID- 1586595 TI - Correlation between protein kinase C activity and histopathological criteria in human colorectal adenoma. AB - We examined protein kinase C (PKC) activity in the cytosolic and particulate fractions of homogenates obtained from 25 colorectal adenomas and adjacent normal mucosa in patients with colorectal carcinoma. The total PKC activity of colorectal adenomas was significantly reduced compared with that of normal mucosa in all cases (122 +/- 45.8 vs 174 +/- 50.5 pmol min-1 mg-1) (means +/- s.d.) (P less than 0.001). The particulate fraction PKC activity of adenomas was also significantly lower than in normal mucosa (71.4 +/- 31.3 vs 115 +/- 39.6 pmol min 1 mg-1) (P less than 0.001). Adenomas were classified by size, histological type and degree of dysplasia. The average particulate PKC activity ratio (adenoma/normal mucosa) of tubulovillous adenomas or those with severe dysplasia was significantly reduced compared with that of tubular adenomas or tumours with mild and moderate dysplasia (both P less than 0.001), while there were no significant differences in the cytosolic PKC activity ratio. The particulate PKC activity ratio decreased significantly with increasing adenoma size (P less than 0.001), while the cytosolic ratio again showed no difference. These findings suggested that the particulate PKC activity ratio had a possible correlation with the malignant potential of colorectal adenomas and that this ratio may be a useful biological indicator of colorectal carcinogenesis. PMID- 1586596 TI - Comparison of the pharmacokinetics, biodistribution and dosimetry of monoclonal antibodies OC125, OV-TL 3, and 139H2 as IgG and F(ab')2 fragments in experimental ovarian cancer. AB - Monoclonal antibody (MAb) 139H2 was previously shown to localise specifically into ovarian cancer xenografts in nude mice. MAb 139H2 was compared with MAbs OC125 and OV-TL 3, all reactive with ovarian carcinomas, for the binding characteristics as IgG and F(ab')2 fragments with the use of the OVCAR-3 cell line grown in vitro and as s.c. xenografts. Immunoperoxidase staining of OVCAR-3 tissue sections with MAbs OC125 and 139H2 was heterogeneous, whereas MAb OV-TL 3 showed homogeneity. No differences in binding were observed between IgG and F(ab')2. The avidity expressed as apparent affinity constants of MAbs OC125, OV TL 3 and 139H2 for OVAR-3 cells were 1 x 10(9) M-1, 1 x 10(9) M-1, and 1 x 10(8) M-1, while the number of antigenic determinants were 5 x 10(6), 1 x 10(6) and 7 x 10(6), respectively. In OVCAR-3 bearing nude mice the blood half-lives of the MAbs as IgG and F(ab')2 were approximately 50 h and 6 h, respectively. Maximum tumour uptake for the whole MAbs OC125, OV-TL 3, 139H2 and a control MAb 2C7 was 8.5%, 17.7%, 11.1% and 2.5% of the injected dose g-1, reached at 72 h after injection. For the respective F(ab')2 fragments, the maximum values were 5.2%, 10.0%, 5.5% and 1.9% of the injected dose g-1, reached between 6 h and 15 h. Tumour to non-tumour ratios were more favourable for the F(ab')2 fragments as compared to those for MAbs as IgG. Biodistribution in mice bearing a control tumour confirmed the specificity of tumour localisation of MAbs OC125, OV-TL 3 and 139H2. After injection of a tracer dose of 10 microCi of radiolabelled MAbs OC125, OV-TL 3 and 139H2 as IgG, tumours received 38 cGy, and 9 cGy. In our OVCAR 3 model, a ranking in efficiency in tumour localisation would indicate MAb OV-TL 3 as most favourable MAb, but cross-reactivity with subpopulations of human white blood cells might hamper its clinical use. Dosimetric data indicate a 4-fold higher radiation absorbed dose to tumours for IgG compared with F(ab')2 fragments. PMID- 1586597 TI - Tumour growth rates in squamous carcinoma of the head and neck measured by in vivo bromodeoxyuridine incorporation and flow cytometry. AB - The cell kinetics of 82 squamous cell carcinomas of the head and neck were studied by in vivo administration of the thymidine analogue, bromodeoxyuridine (BrdUrd). Ploidy, BrdUrd labelling index (LI), duration of S-phase (Ts), potential doubling time (Tpot) and S-phase fraction (SPF) were measured by flow cytometry on 50 microns paraffin embedded sections. The range of values obtained compared well with other in vivo cell kinetic studies of head and neck cancer. Aneuploid tumours had a significantly higher BrdUrd labelling index and SPF, and a short Tpot than diploid tumours. To validate the use of 50 microns sections for measuring cell kinetic parameters by flow cytometry a comparison of values obtained by 50 microns sections and small blocks of tissue was made. No significant difference was found between the two methods. Reproducibility of values between two consecutive thick sections was also good. We conclude that reproducible cell kinetic measurements can be made in tumour samples using 50 microns sections of BrdUrd labelled tissue. PMID- 1586598 TI - In vivo anti-tumour activity of FCE 23762, a methoxymorpholinyl derivative of doxorubicin active on doxorubicin-resistant tumour cells. AB - FCE 23762 is a new doxorubicin derivative obtained by appending a methoxymorpholinyl group at position 3' of the sugar moiety. The compound is greater than 80 times more potent than doxorubicin, it is highly lipophilic, and presents equivalent anti-tumour activity when administered by i.p., i.v. or oral route. The pattern of anti-tumour activity of FCE 23762 differs from that of doxorubicin in maintaining anti-tumour activity against two P388 murine leukaemia sublines resistant to doxorubicin and, although at borderline levels of efficacy, against LoVo human colon adenocarcinoma resistant to doxorubicin. FCE 23762 exhibits remarkable efficacy against MX-1 human mammary carcinoma, with most treated mice being cured both after i.v. and oral treatment. Anti-tumour activity was also observed against L1210 murine leukaemia and two sublines resistant to cis-platinum and melphalan, M5076 murine reticulosarcoma, MTV murine mammary carcinoma and N592 human small cell lung cancer. PMID- 1586599 TI - P53 mutations in gastric carcinomas. AB - We carried out an immunohistochemical study and DNA analysis of 30 gastric carcinomas to evaluate p53 overexpression and allelic loss at 17p. The immunohistochemical study demonstrated immunoreactivity for p53 protein in four cases. Allelic loss for the pYNZ22.1 marker was detected in nine cases. In total, ten cases showed immunoreactivity for p53 protein, allelic loss, or both. The study of nine of these cases by constant denaturant gel electrophoresis revealed p53 mutations in three cases. We conclude that the prevalence of mutations of p53 in our series is similar to what has recently been observed in other cases of gastric cancer, but lower than in colon carcinomas. PMID- 1586600 TI - Intravenous interleukin-2 in patients over 65 with metastatic renal carcinoma. AB - The present study was designed in order to evaluate the response rate and the toxicity of continuous infusion of Interleukin 2 (IL2) in patients over 65 with metastatic renal cell carcinoma. Twenty-five patients, median age 69 (range 65 77), without any prior systemic anticancer therapy received a continuous infusion of IL2 at a dose of 18 x 10(6) iu m-2 d-1 for 2 periods of 5 days separated by a 6 day break. Toxicity was not different compared with younger patients (e.g. fever, hypotension, rise in creatinine level), except for cardiac toxicity which was of great concern. Despite normal cardiac tests prior to inclusion into the study, abnormalities of the cardiac rhythm ranging from tachycardia to ventricular extrasystoles occurred in 44% of the patients and IL2 cardiac toxicity was responsible for one toxic death. Three objective responses, i.e. one partial and two complete persistent responses, were seen in 22 evaluable patients. Thus, if age does not seem to modify the potential for response to IL2 therapy, cardiac toxicity appears as a limiting factor for intravenous schedules of IL2. PMID- 1586601 TI - The effect of the synthetic retinoid etretinate on sputum cytology: results from a randomised trial. AB - Laboratory studies, and one previous uncontrolled trial, have suggested that retinoids may reverse bronchial atypia, a putatively premalignant condition. Sputum sampling is a simple, non-invasive method of assessing atypia. Smokers with at least a 15 pack-year history were screened for sputum atypia. One hundred and fifty subjects' were randomised to receive the synthetic retinoid etretinate 25 mg orally or identical placebo daily for 6 months. Compliance was measured by performing pill counts and serum sampling every 2 months for etretinate levels. The outcomes assessed were, improvements in sputum atypia and toxicity. At baseline there was no significant difference between the two groups with respect to gender, smoking history or extent of atypia. Four of 75 subjects on etretinate and six of 75 on placebo dropped out before 6 months. Compliance as measured by pill counts and etretinate levels was high. Eighty-six per cent of subjects on etretinate took 90% or more of their prescribed medication and etretinate was detected in 245 of 264 samples. By contrast etretinate was detected in only six of 266 samples in the control group and probably did not represent true contamination. After 6 months on etretinate there was no difference in the degree of atypia between the two treatment arms. Toxicity was mild in both groups with considerable placebo effect noted. Etretinate, at the dose used in this study, had no impact on sputum atypia as detected by sputum sampling. PMID- 1586603 TI - 'VEEP' in children with Hodgkin's disease--a regimen to decrease late sequelae. AB - In an attempt to decrease the risk of second malignancies and future infertility in children with Hodgkin's disease (HD) while retaining acceptable remission rates, an anthracycline based regimen containing no alkylating agent has been devised. VEEP contains vincristine, epirubicin, etoposide and prednisolone given at 3 weekly intervals. Forty-four patients, aged 2-15 years, have been treated: ten relapsed patients and 34 previously untreated with chemotherapy (including three relapsed stage I treated initially with radiotherapy). The median follow up for all patients is 25 months (range 6-52 months). The response rate in previously treated patients was 80% (95% CI 44-97%) and five remain alive in remission. The response rate in untreated patients was 88% (95% CI 72-97%) with 62% CR + CR(u) (uncertain/unconfirmed) (95% CI 44-77%). Of four patients who had a final response of CR(u) three have relapsed at 9, 16 and 38 months. Two of the children in CR have relapsed at 6 and 16 months. The relapse free rate at 3 years is 67% (95% CI 17-82%). In this pilot study the event free survival appears somewhat poorer than conventional combinations and further follow up is required to confirm the salvagability of relapsed patients. PMID- 1586602 TI - A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part I: Clinical aspects. AB - The optimal schedule for recombinant interleukin-2 (rIL-2) administration is unclear. Because the clinical and immunological effects of prolonged continuous exposure to rIL-2 are unknown, we have conducted a phase I study to assess the toxicity and feasibility of continuous low dose infusion of rIL-2 (EuroCetus) using central venous access with a portable infusion device on an out-patient basis. Twenty-two patients entered the study, 13 with melanoma and nine with renal cell cancer, age range 26-66 years (median 51), performance status less than or equal to 1. They were treated with one of the following doses per m2 per 24 h: 0.18 x 10(6) IU, 0.6 x 10(6) IU, 1.8 x 10(6) IU, 3 x 10(6) IU, 6 x 10(6) IU and 9 x 10(6) IU. Toxicity was evaluable in 20 patients receiving greater than or equal to 3 weeks treatment duration or in whom treatment was discontinued prematurely because of toxicity. Constitutional symptoms consisting of fatigue, malaise and fever up to 40 degrees C without significant organ dysfunction occurred with doses greater than or equal to 1.8 x 10(6) IU m-2. The maximum tolerated dose was 6 x 10(6) IU m-2 24 h-1. In all patients toxicity reached a peak at 3 weeks and resolved thereafter despite continued rIL-2 treatment. Peripheral blood eosinophilia (up to 66% of white blood cell count) followed the same pattern. An infection of the central venous access occurred in 55% of the patients but this was mostly asymptomatic. Thirteen patients were treated greater than or equal to 6 weeks and were evaluable for tumour response. A partial remission occurred in a patient with melanoma with a dose of 1.8 x 10(6) IU rIL-2 m-2 24 h-1. PMID- 1586604 TI - Locally advanced breast cancer: report of phase II study and subsequent phase III trial. AB - Twenty-four evaluable patients with stage T4 breast cancer were entered into a phase II study and received chemotherapy comprising cyclophosphamide 1,000 mg m-2 i.v., doxorubicin 50 mg m-2 i.v., vincristine 1.4 mg m-2 i.v. and prednisolone 40 mg orally for 5 days, given 3 weekly for four cycles prior to undergoing loco regional radiotherapy. All patients completed treatment as planned with no major acute toxicity from either chemotherapy or radiotherapy. Subsequently 52 patients with stage T4 breast cancer were randomised in a phase III trial to receive either radiotherapy alone (RT) or this chemotherapy and radiotherapy (CHOP + RT). A significantly higher complete response rate was achieved in the CHOP + RT treatment arm (P = 0.03). However a larger proportion of the RT arm achieved loco regional control after salvage treatment for relapse such that 50% of the RT arm and 57% of the CHOP + RT arm had no evidence of loco-regional disease at the time of last follow-up or death. There was no statistical difference in time to distant relapse or overall survival. Analysis of the pilot study showed results comparable to the trial CHOP + RT arm. This trial suggests that this cytotoxic therapy used in conjunction with radiotherapy has only marginal value in improving prognosis in locally advanced breast cancer. PMID- 1586605 TI - Preliminary results of the use of urinary excretion of pyridinium crosslinks for monitoring metastatic bone disease. AB - The collagen crosslinks, pyridinoline and deoxypyridinoline, are recently described markers of the rate of bone resorption. The urinary excretion of these compounds, expressed as a ratio to urinary creatinine, has been measured using ion-pair reversed phase high-performance liquid chromatography in 20 patients receiving oral pamidronate for bone metastases from breast cancer. Before treatment the ratio of pyridinoline and deoxypyridinoline to creatinine in urine (UPCR and UdPCR respectively) were each above normal in 16/20 (80%) patients. Urinary calcium excretion (UCCR) was elevated in 15/20 (75%). There was a strong correlation between UPCR and UdPCR, but neither of the crosslink measurements correlated well with UCCR. Urinary excretion of all three indices of bone resorption fell significantly during pamidronate treatment. The median values after 4 weeks treatment were 63% of baseline for UPCR, 45% for UdPCR and 26% for UCCR. From this preliminary study urinary pyridinoline and deoxypyridinoline excretion appear to be promising markers of bone resorption in advanced malignancy. Their role in response assessment and the advantages over UCCR measurements merit further study. PMID- 1586606 TI - Reproductive factors and risk of thyroid cancer. A prospective study of 63,090 women from Norway. AB - This prospective study of 63,090 Norwegian women with 124 cases of thyroid cancer diagnosed during 1961-1989 revealed no strong associations with reproductive factors. Late last birth was related to increased risk, whereas no association was noted with parity. A long reproductive period was related to increased risk of papillary carcinomas, whereas a decreased risk of follicular carcinomas and other adenocarcinomas was observed in women with early menarche and late menopause. The risk of thyroid cancer was significantly increased among women in the occupational category 'fishing, ships officers and crew'. Our results are consistent with a modest effect of certain reproductive factors upon thyroid cancer development. PMID- 1586607 TI - Surveillance following orchidectomy for stage I testicular seminoma. AB - An analysis of the primary tumour histopathology was performed on 103 patients managed by orchidectomy and surveillance for stage I seminoma. Patients have been followed for 14-141 months (median 62 months) after orchidectomy. Seventeen patients relapsed, the probability of remaining relapse free at 5 years being 82% (95% confidence intervals, 74%-88%). No patients died of progressive germ cell tumours. The only significant histological factor predicting relapse was the presence of lymphatic and vascular invasion. Four of 42 patients with neither lymphatic or vascular invasion recurred, nine of 53 patients with either lymphatic or vascular invasion recurred and three of eight cases with both lymphatic and vascular invasion recurred (P = 0.05-trend). Though initial recurrence was usually of moderate volume and confined to para-aortic nodes, eight patients were treated with chemotherapy either because of the extent of their initial relapse (four cases), or because of subsequent relapse (four cases). In view of the difficulties of identifying patients at risk and of detecting early relapse, surveillance for stage I seminoma should remain a research protocol. PMID- 1586608 TI - Nausea in cancer chemotherapy is inversely related to urinary cortisol excretion. PMID- 1586609 TI - Clinical correlation of high activity dynamic hepatic scintigraphy in patients with colorectal cancer. AB - The hepatic perfusion index, the ratio of hepatic arterial to total liver blood flow, was measured in 50 consecutive patients with colorectal cancer using radiolabelled colloid with high administered activity. In patients with proven liver metastases the diagnostic sensitivity of the HPI was 96% and the predictive value of a negative test was 92%. Dynamic hepatic scintigraphy is of value in the management of patients with colorectal cancer. PMID- 1586610 TI - Carcinoma of the cervix uteri: an assessment of the relationship of tumour proliferation to prognosis. AB - The aim of this study was to ascertain whether assessing the growth fraction of cervical carcinoma of 28 patients, using antibody Ki-67, would be of value in clinical practice. The results showed no relationship between growth fraction and age, clinical stage, lymph node involvement or short term (3-5 years) survival. PMID- 1586611 TI - Refusal in testicular cancer patients: implications for surveillance. PMID- 1586612 TI - Soviet cancer treatment and research: an eyewitness report. PMID- 1586613 TI - American Cancer Society Medal of Honor to Gianni Bonadonna. PMID- 1586614 TI - To CHOP or not to CHOP ... is that the question? PMID- 1586615 TI - The fate of abstracts submitted to a cancer meeting: factors which influence presentation and subsequent publication. AB - Abstracts that are published in the proceedings of meetings receive minimal peer review, but may be referenced or used to make decisions about management of patients. We have studied factors which influence the probability of acceptance for presentation, and of subsequent publication of articles, from abstracts included in the Proceedings of the American Society of Clinical Oncology (ASCO). From a random sample of 197 abstracts submitted to the 1984 meeting, 81 were accepted for presentation and a Cancerline computer search revealed 103 papers that were published subsequently in peer-reviewed journals. Communication with authors of the remaining abstracts led to identification of 12 additional articles that had been published. Major reasons for non-publication were insufficient priority or lack of time, funds or other resources. Abstracts which reported 'positive' results were more likely to be presented than those reporting 'negative' results (60% vs. 35%, p = 0.03) and to lead to subsequent publication (74% vs. 32%, p = 0.0001). Of the 81 abstracts in our sample that were selected for presentation at the meeting, 63 (78%) led to publications, compared to 45% (52/116) of those not selected (p = 0.00001). There were no significant differences in the frequency of citation of abstracts that did or did not lead to subsequent publications. We made detailed comparisons of abstracts and subsequent papers for 18 randomized phase III trials. For 15 studies (83%), there was good correlation between the conclusions of the article and of the abstract.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586616 TI - Sixth World Conference on lung cancer -- Melbourne, November 10th-14th, 1991. PMID- 1586617 TI - Combined modality adjuvant treatment of high-risk rectal cancer: a treatment of choice or a choice of treatment? PMID- 1586619 TI - A multicenter phase II study of carboplatin in advanced ovarian carcinoma: final report. AB - A phase II trial of single-agent carboplatin in advanced ovarian cancer was performed by 19 institutions from 10 European countries. A total of 260 patients were treated, with a median age of 55 (range: 20-79) years. Karnofsky performance status was 80-100 in about two-thirds of the patients. Prior therapy consisted of surgery only in 31 patients, irradiation in 9, chemotherapy without cisplatin in 45, and with cisplatin in 175. Carboplatin was administered as second-line therapy in about one-half and as third-line or more in one additional third of the study population. Initial dose was 400 mg/m2 in 90, 360 mg/m2 in 152, and 320 mg/m2 or less in 18 patients. A total of 971 courses (mean 3.7, median 2, range: 1-13) of therapy were administered. A total of 16 complete and 46 partial responses were observed in 226 evaluable patients, for an objective response rate of 27%. Efficacy was greater in chemotherapy-untreated patients (51% vs. 23%, p = 0.002). In cisplatin-pretreated patients activity was significantly higher in non refractory patients (26% vs. 4%, p = 0.015). Myelosuppression was the most significant side effect. However, low hematologic counts seldom translated into clinically significant complications. Patients with impaired baseline creatinine clearance and poor performance status were at higher risk of developing severe myelosuppression during the initial course of treatment. Non hematologic side effects were rare and mild, except for emesis. Carboplatin has a definite role in the treatment of ovarian cancer, but almost complete cross-resistance with the parent compound was observed clinically. PMID- 1586618 TI - Results of a randomized study of previously-untreated intermediate and high grade lymphoma using CHOP versus CNOP. AB - A randomized multicenter phase III study was conducted to compare the efficacy and toxicity of CHOP and CNOP in intermediate and high-grade non-Hodgkin's lymphoma. CHOP consisted of cyclophosphamide 750 mg/m2, vincristine 1.4 mg/m2, doxorubicin 50 mg/m2 on day 1 and prednisone 50 mg/m2 on days 1 to 5. The CNOP regimen was identical to CHOP except for replacement of doxorubicin by 10 mg/m2 mitoxantrone. Patient characteristics were evenly distributed in the two arms, except for age and stage, which slightly favoured the CHOP arm. The rate of complete remission was 70% (31/44) in patients treated with CHOP and 51% (23/45) in those receiving CNOP (P = 0.09). At 48 months and with a median follow-up of 41 months, 44% of the complete responders treated with CHOP and 64% of those treated with CNOP were estimated to still be in their first complete remission (P = 0.14), while 31% and 34% remained alive and free of progression. The Kaplan Meier estimate of overall survival at 48 months is 53% and 50%, respectively. The higher response rate obtained with CHOP probably reflected a less aggressive lymphoma population. The mean WBC nadir was 2.0 x 10(9)/l for CHOP and 1.8 x 10(9)/l for CNOP. One and three patients, respectively, died during induction. Nausea, vomiting and cardiac toxicity were similar. More alopecia and mucositis were observed with CHOP. We conclude that CHOP and CNOP have similar toxicities and are equivalent in previously untreated non-Hodgkin's lymphoma in terms of complete response rate, event-free survival and overall survival. PMID- 1586620 TI - A phase II trial of 10-ethyl-10-deaza-aminopterin, a novel antifolate, in patients with advanced and/or recurrent squamous cell carcinoma of the head and neck. The EORTC Head and Neck Cancer Cooperative Group. AB - Forty-seven patients with advanced and/or recurrent squamous cell carcinoma of the head and neck were treated with 10-ethyl-10-deaza-aminopterin (10-EdAM), a new analogue of methotrexate. The drug was given as a weekly i.v. bolus injection, starting at 80 mg/m2 with two dose increments of 10% if no toxicity was observed after two weeks. Only patients with tumors of the larynx, oral cavity, oropharynx and hypopharynx were included in the trial. Eighty-two percent of the patients had had prior surgery and/or radiotherapy. Forty-four patients were evaluable for response and toxicity. Five CR (12%) and five PR were obtained, yielding a response rate of 24% (CR+PR). The toxicity was similar to that usually seen with methotrexate; stomatitis and skin toxicity were rather pronounced. The data suggest that 10-EdAM has activity similar to that of methotrexate in patients with head and neck cancer. PMID- 1586621 TI - Therapy of relapsed or refractory low-grade follicular lymphomas: factors associated with complete remission, survival and time to treatment failure. AB - Patients with relapsed low-grade follicular lymphomas (LGFL) frequently respond to subsequent therapy and can have long survival, but are rarely cured. Factors associated with complete remission (CR) rate, length of survival, and time to treatment failure (TTF) after relapse are not well known. We assessed such factors by multivariate analysis in a retrospective review of 95 patients with relapsed LGFL treated with investigational chemotherapy regimens at our institution. The CR rate after therapy was 22%; the likelihood of achieving CR was inversely associated with the number of previous treatment failures (P less than 0.001) and serum LDH level (P less than 0.05). Both the presence of constitutional symptoms and a history of more than two previous treatment failures were associated with shortened survival and TTF. Hemoglobin level was also significantly associated with survival. Prognostic models for survival and TTF were derived to define patient groups with different projected outcomes after therapy for relapsed disease. The results of this study can be used to select patients for new investigational treatments and to evaluate the outcome of such therapies. PMID- 1586622 TI - Antitumor activity of 1,4-bis (2'-chloroethyl)-1,4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis Maleate) in M5076 and its subline resistant to cyclophosphamide M5/CTX. AB - We investigated the antitumoral activity of Dabis Maleate given on different dosage schedules and as continuous infusion in a murine reticular cell sarcoma M5076 (M5) and in a subline made resistant to cyclophosphamide and other nitrogen mustards (M5/CTX). The therapeutic index of Dabis Maleate was clearly better when the drug was given as a continuous 72-h infusion. Dabis Maleate appeared non cross-resistant to cyclophosphamide and this property renders it interesting for further clinical development. PMID- 1586623 TI - Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study. AB - From May 1988 to March 1990, 17 consecutive patients with histologically proven malignant mesothelioma were treated with epirubicin 75 mg/sqm i.v. on day 1 and ifosfamide 1.8 gr/sqm/day i.v. from day 1-5. Treatment was repeated every 3 weeks until progression. Fifty-three chemotherapy cycles were administered to the 17 patients treated (median, 3 cycles/patient). No complete responses, 1 partial response, 8 stable diseases and 8 progressions were noted. Toxocity was acceptable and no treatment-related deaths occurred. Actuarial median survival was 6 months. In this study, a combination of full doses of epirubicin and ifosfamide did not prove to be active in malignant mesothelioma. PMID- 1586624 TI - Allergic reactions to carboplatin. PMID- 1586625 TI - Frequent administration of Dabis Maleate, a phase I study. AB - Dabis Maleate (1,4-bis(2'-chloroethyl)-1,4-diazabicyclo[2.2.1] Heptane dihydrogen dimaleate) (NSC 262666) is an alkylating quaternary nitrogen compound. In a previous phase I study using a once-every-3-weeks administration the dose limiting toxicity was neurotoxicity and the recommended dose for phase II studies was 750 mg/m2 iv every 3 weeks. In vitro studies suggested a higher activity after more frequent administration, and in vivo studies a better therapeutic index with prolonged infusion. We studied 11 patients with solid tumors. Dose levels tested ranged from 250-750 mg/m2, either as a day 1-3 regimen or weekly, the latter as bolus administration or as prolonged infusion. The dose-limiting toxicity was neurotoxicity consisting of paresthesias and ataxia. Nausea and vomiting were moderate. No other major toxicity was observed. The dose recommended for phase II studies is 500 mg/m2/week as a 6-hour iv infusion for 6 weeks, followed by a 3-week rest period. PMID- 1586626 TI - Angioneurotic oedema and urticaria during therapy with interleukin-2 (IL-2). PMID- 1586627 TI - Best treatment for colorectal cancer and confirmatory trials. PMID- 1586628 TI - Primary tumour mutant p53 gene protein and epidermal growth factor receptor expression and doxorubicin plus ifosfamide for recurrent breast cancer. PMID- 1586629 TI - The role of gonadotrophin-releasing hormone analogues in the management of prostate cancer. PMID- 1586630 TI - Immunization against infectious disease in adult oncology. PMID- 1586631 TI - Chest radiography or computed tomography in the assessment of lung cancer prior to radiography. AB - A series of 93 patients with lung cancer were considered for intensive radiotherapy, and investigated by chest radiography and computed tomographic (CT) scan. Spread of tumour was detected radiologically to lymph nodes, pleura or chest wall on 98 occasions. Of these, 16 were shown by both investigations, but in 82 the spread was revealed only by CT examination. Clear visualization of the tumour prior to radiotherapy is important to select those patients who would benefit from radical radiotherapy, to allow accurate treatment planning, and to allow, in subsequent follow-up, monitoring of the response to radiotherapy. In this study tumour was clearly visualized in 59 patients treated, but in 31 (53%) of these only by the use of computed tomography. PMID- 1586632 TI - Chest radiography or computed tomography to assess the response of lung cancer to radiotherapy. AB - In 58 patients with lung cancer the response of the primary tumour to treatment with CHART was followed by both chest radiograph and computed tomographic (CT) scan. Clear evidence of complete response was seen by chest radiograph in 11 patients and by CT scan in 20. If all studies showing no definite tumour, regardless of the quality of the study, were included then complete response was considered to have occurred in 25 as indicated by chest radiograph and in 22 by CT scan. The validity of the observations was tested by life table analysis comparing the survival of those showing complete regression with those whose response was incomplete. Comparison based on the CT scan findings showed the greatest significance (P = 0.0001), while that based on the chest radiograph findings showed the least (P = 0.044). PMID- 1586633 TI - Para-aortic nodal irradiation for early stage testicular seminoma. AB - Early stage seminoma of the testis has an excellent prognosis when post orchidectomy para-aortic and ipsilateral pelvic radiotherapy is given. However, studies on testicular lymphangiograms and the rarity of isolated pelvic nodal disease suggest that pelvic radiotherapy is not necessary, except in cases where there is the possibility of altered lymphatic drainage. We report on 27 patients with stage I and IIA seminoma treated between 1983 and 1989. Seventeen patients received radiotherapy to the para-aortic region only. There have been no pelvic recurrences. No long term complications have been encountered. We discuss the reported data which suggest that a reduced complication rate should result from the proposed field reduction. We conclude that irradiating only the para-aortic region in early stage seminoma is logical, should not increase the relapse rate and should reduce the complication rate. PMID- 1586634 TI - Phase I study of intravenous fosquidone (GR63178A-NSC D611615) using a three times a week schedule. AB - In a Phase I study fosquidone was administered to 23 patients (15 female, 8 male; mean age 53.6 years) with various solid tumours. Increasing doses (50-325 mg/m2) were given intravenously three times a week for 3 weeks. The MTD was established a 325 mg/m2 dose, the dose limiting factor being phlebitis in two of three patients. The other main side-effects were headache (9 patients), pain (11 patients) and nausea and vomiting (16 patients). The majority of these were mild (WHO grade 1-2), but two patients reported WHO grade 3 and 4 pain. There was no clear relationship between dose, severity and frequency of side-effects. Four tumour regressions (three minor and one partial response) were achieved at varying dose levels (50, 100, 160 and 325 mg/m2) in patients with different tumours (laryngeal, colorectal and lung). The recommended dose for Phase II studies is 250 mg/m2 given intravenously three times a week for 3 week. PMID- 1586635 TI - An audit of travel and waiting times for outpatient radiotherapy. AB - The object of this study was to assess the non-medical factors which detract from the quality of outpatient receiving service to a population of 2.7 million in a wide geographical area. We conducted a survey by patient questionnaire of all outpatients receiving radiotherapy in the West of Scotland on a single day in 1990. A total of 216 outpatients attended for radiotherapy with a 92% response rate to the questionnaire being achieved. Median values (and ranges) were: age 58 (4-85) years, number of daily treatments 20 (4-33), distance travelled in one direction 10 (1-60) miles, travelling time 45 (5-130) minutes, waiting time in the unit for treatment 60 (0-200) minutes, and a time away from home of 2 hours 50 minutes (35 minutes-7 hours). Sixteen per cent of patients had a relative who lost time from work by transporting the patient and only 12 of 60 patients who were away from home over a meal time were offered a hospital meal. Sixteen per cent of patients came by ambulance and 73% by motor car. Of 146 travelling by car 27% used a charity service and 20% a volunteer driver ambulance service car. It is concluded that long travelling distances, travelling times and treatment waiting times for many patients require revision of transport provision, a strict appointment system, more treatment machines and hostel accommodation. PMID- 1586636 TI - Childhood cancer in the West Midlands: incidence and survival, 1980-1984, in a multi-ethnic population. AB - The purpose of this study is to describe the incidence and survival of childhood cancer in the West Midlands for the period 1980-1984. Proportional breakdown by Asian subgroup is also considered. A total of 587 patients were registered, 49 of them of Asian origin. Breakdown to Asian versus non-Asian subgroups by diagnosis revealed comparatively high rates for Hodgkin's disease, retinoblastoma and neuroblastoma in the Asian patients. However, a deficit of cases was seen for CNS tumours. Comparison of overall age-standardized rates (ASR) for all cancers revealed a substantially lower value compared to that reported for the USA white population but a similar value to the USA black and UK white populations. Diagnostic breakdown revealed that the major difference between the West Midlands Regional Children's Tumour Research Group (WMRCTRG) and the USA white ASR was in the leukaemia and lymphoma group. Overall survival for the series was 56% at 5 years. The poorest prognosis was found in acute myeloid leukaemia, with only 23% of patients surviving at 5 years, against 62% in acute lymphoblastic leukaemia. CNS tumours also had a poor outcome, with an overall survival rate of 47%, although certain individual diagnoses were more favourable. We observed a 100% survival rate in Hodgkin's disease up to 5 years from diagnosis, and both Wilms' tumour and retinoblastoma had 90% survival rates. PMID- 1586637 TI - The role of routine urine and parametrial aspirate cytology in staging carcinoma of the cervix. AB - The role of routine urine and parametrial aspirate cytology as a means of refining the staging of carcinoma of the cervix was assessed in a series of 45 consecutive patients undergoing examination under anaesthetic and cytoscopy. Only 2/45 (4%) of urine samples were positive and 3/37 (8%) of parametrial aspirates were abnormal. In none of these patients was additional information obtained over that already available from cytoscopy, digital examination and routine radiology. These procedures have no role in the routine clinical staging of cervical carcinoma. PMID- 1586638 TI - High-dose-rate remote afterloading irradiation of carcinoma of the cervix in Hong Kong: unexpectedly high complication rate. AB - One hundred and thirty-six patients with biopsy-proven carcinoma of cervix were treated with external beam irradiation to the whole pelvis (46 Gy in 23 fractions) and three weekly applications of high-dose-rate (HDR) intracavitary brachytherapy of 7 or 8 Gy per fraction to point A (2 cm above and 2 cm lateral to the cervical os). The actuarial 5-year survival rate was 72% (Stage IB 85%; IIA 64%; IIB 70%; IIIA 25%; IIIB 53%). Patient age above 61 years and Stage III disease were adverse determinants for survival as shown by multivariate analysis. Late complications developed in 47% (65/137) of patients. Grade 3 or above complications occurred in the bladder, small bowel and sigmoid colon/rectum in 5%, 3% and 7% of patients, respectively. The most significant determinant of severe rectal complications was the addition of a lower vaginal tandem (P less than 0.01); the other determinants of rectal complications included a uterine length greater than 5 cm, a total biologically effective dose to the rectum of more than 120 Gy3 and Stage III disease. PMID- 1586639 TI - Successful pregnancy following tailor-made intracavitary radiotherapy for microinvasive adenocarcinoma of the endocervix. AB - We report a case of microinvasive adenocarcinoma of the endocervix in a lady anxious for a family. Intracavitary radiotherapy using a specially designed 125-I bearing applicator allowed radical treatment of the endocervix whilst sparing the endometrium and ovaries and preserving fertility. The patient remains well and disease free following a successful pregnancy. PMID- 1586640 TI - Intra-abdominal panniculitis can mimic recurrent stomach carcinoma. AB - Carcinoma of the stomach is increasingly treated with chemotherapy. We describe two cases of intra-abdominal panniculitis in patients after laparotomy and chemotherapy for stomach carcinoma. Intra-abdominal panniculitis can result in mass lesions in the mesentery and omentum. The diagnosis should be considered in patients who have undergone chemotherapy for stomach carcinoma and who develop abdominal masses. PMID- 1586641 TI - The spontaneous regression of lymphoma in AIDS. AB - Non-Hodgkin's lymphomas are an increasing problem in the AIDS population. They are generally aggressive, high-grade lymphomas and more commonly present at extranodal sites, particularly the central nervous system. Although chemo- and radiosensitive, the duration of response is generally short lived. Spontaneous remission of non-Hodgkin's lymphomas has been reported in immunocompetent individuals, but has not been reported in HIV disease. We would like to report the first such case. PMID- 1586642 TI - Acute non-lymphocytic leukaemia and myelofibrosis following sequential hemibody irradiation for prostatic carcinoma. PMID- 1586643 TI - Economical with the radiotherapy 'dose'. PMID- 1586644 TI - Nonlagged relay cells and interneurons in the cat lateral geniculate nucleus: receptive-field properties and retinal inputs. AB - Simultaneous recording in the cat's retina and lateral geniculate nucleus (LGN) was used to find excitatory inputs to LGN cells. These recordings, correlated with measurements of LGN cell receptive-field properties, suggested new functional subdivisions of LGN cells. Distinctions between lagged and nonlagged cells were described before (Mastronarde, 1987a,b; Mastronarde et al., 1991), classification of nonlagged cells is examined here. The XS-type relay cells described before (Mastronarde, 1987a,b) each had detectable excitatory input from only one retinal X cell. Cells that received significant input from more than one retinal X cell were of three kinds: relay cells with pure X input (XM); relay cells with mixed X and Y input (X/Y); and cells that could not be antidromically activated from visual cortex (XI). In the series of relay cells, XS-XM-X/Y-Y, cells had progressively larger receptive-field centers, lower spatial resolution, and faster and more Y-like responses to various stimuli. XI cells resembled XM and X/Y cells in some respects but tended to have higher maintained firing rates, more sustained responses, and weaker surround suppression of the center response. The distinctness of XS, XM, X/Y, XI, and Y from each other was examined with a modification of discriminant analysis that allowed cells to lack measurements for some parameters. Any given pair of categories could be distinguished reliably with only three parameters, although less so for X/Y-Y. In particular, XI cells were distinguishable from relay cells by properties other than the results of cortical stimulation, thus supporting the identity of XI cells as a separate class of X interneurons. Two discontinuities in the behavior of retinal input suggest that XM cells are a separate class from XS and X/Y cells: (1) LGN X cells received either no detectable input from any of the retinal X cells adjacent to their main input, or an easily detectable amount from several such cells; and (2) cells received either no Y input or a certain minimum amount. No such discontinuity in input underlies the distinction between X/Y and Y cells. LGN Y cells were also heterogeneous. Those with substantial input from more than one retinal Y cell had larger receptive fields and a greater preference for fast moving stimuli than did Y cells dominated by a single input. Three Y cells could not be antidromically activated. They tended to differ from Y relay cells and resemble X interneurons in several ways.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1586645 TI - Three types of GABA-immunoreactive cone horizontal cells in teleost retina. AB - Peroxidase-anti-peroxidase immunocytochemistry, applied on serial semithin epoxy resin sections, was used to examine the localization of endogenous GABA in horizontal cells in the retina of a marine teleost, the dragonet (Callionymus lyra L.). The immunostaining shows that not only the external H1 cone horizontal cells label with antibodies against GABA, but also the H2 and H3 cone horizontal cells in the inner nuclear layer. The distribution of the H1 cells corresponds to that of the single cones. They are square-patterned and in the dorsal retina their density equals 20,000 cells/mm2. The estimated density of the immunostained H2 and the H3 cells in the dorsal retina is 9500 and 1300 cells/mm2, respectively. The H2 and H3 cells are not geometrically arranged, but nearest neighbor analysis shows that these horizontal cell types do have a very regular disposition. We suggest that GABA is the likely neurotransmitter substance used by all cone horizontal cell types in teleost retina. PMID- 1586646 TI - Effects of the dopamine antagonist (+)-SCH 23390 on intracellularly recorded responses of ganglion cells in the rabbit retina. AB - The effects of the dopamine D1 antagonist (+)-SCH 23390 on the responses of ganglion cells in the superfused rabbit retinal preparation were studied by intracellular recording. At low micromolar concentrations, (+)-SCH 23390 hyperpolarized OFF-center brisk ganglion cells and reduced or abolished any spontaneous spike activity that was present. The light-evoked EPSPs at the onset of a spot or annulus were reduced or abolished, while the EPSPs at light offset were in most cases potentiated. (+)-SCH 23390 depolarized ON-center brisk ganglion cells and increased spontaneous spike activity. The light-evoked EPSPs to spots and annuli were either unaffected or reduced roughly to the same extent. The findings in this study are compared with findings in a recent study in which the effects of (+)-SCH 23390 on the extracellularly recorded responses of ganglion cells in the rabbit retina were examined. PMID- 1586647 TI - Spatial zones of binocular rivalry in central and peripheral vision. AB - This paper presents results from psychophysical experiments on human binocular rivalry in central and peripheral vision. Results show that the incidence of periods of exclusive visibility of a given eye's rival target increased with decreasing target size, and for a given sized target exclusive visibility increased with retinal eccentricity. Control measures confirmed that these results were not attributable solely to reduced peripheral acuity, to Troxler's effect, or to spatial frequency. We computed the minimum-sized stimulus that would lead to a criterion level of exclusive visibility of one or the other eye; this we term the spatial zone of binocular rivalry. The change in estimated size of spatial zones of rivalry with eccentricity compares favorably with estimates of human cortical magnification. We propose a model that assumes concentrically organized zones of rivalry. These zones do not function independently, but instead exhibit a high degree of mutual excitatory cooperativity. The model has multiple solutions for the foveal zone size, but the best fits predict a diameter of 5.3 or 7.3 min of visual angle; these values dovetail nicely with our empirical estimates of the foveal zone size. PMID- 1586648 TI - Blockers of potassium channels reduce the outward dark current in rod photoreceptor inner segments. AB - The dark current of single isolated toad rods was monitored by drawing either the inner segment or the outer segment into a suction electrode. The potassium channel blockers tetraethylammonium (TEA) and 3,4-diaminopyridine (DAP) reduced the amplitude of the dark current when applied to the inner segment. Both drugs were less effective when applied to the outer segment, suggesting that they act at the inner segment to block part of the outward path for the dark current. In addition, DAP affected the kinetics of the light response, possibly by affecting internal pH. PMID- 1586649 TI - Contrast gain control in the primate retina: P cells are not X-like, some M cells are. AB - Primate retinal ganglion cells that project to the magnocellular layers of the lateral geniculate nucleus (M) are much more sensitive to luminance contrast than those ganglion cells projecting to the parvocellular layers (P). We now report that increasing contrast modifies the temporal-frequency response of M cells, but not of P cells. With rising contrast, the M cells' responses to sinusoidal stimuli show an increasing attenuation at low temporal frequencies while the P cells' responses scale uniformly. The characteristic features of M-cell dynamics are well described by a model originally developed for the X and Y cells of the cat, where the hypothesized nonlinear feedback mechanism responsible for this behavior has been termed the contrast gain control (Shapley & Victor, 1978, 1981; Victor, 1987, 1988). These data provide further physiological evidence that the M cell pathway differs from the P-cell pathway with regard to the functional elements in the retina. Furthermore, the similarity in dynamics between primate M cells and cat X and Y retinal ganglion cells suggests the possibility that P cells, being different from either group, are a primate specialization not found in the retinae of lower mammals. PMID- 1586650 TI - Light-sensitive melatonin synthesis by Xenopus photoreceptors after destruction of the inner retina. AB - Several lines of evidence indicate that retinal photoreceptors produce melatonin. However, there are other potential melatonin sources in the retina, and melatonin synthesis can be regulated by feedback from the inner retina. To analyze cellular mechanisms of melatonin regulation in retinal photoreceptors, we have developed an in vitro method for destruction of the inner retina that preserves functional photoreceptors in contact with the pigment epithelium. Eyecups, which include the neural retina, retinal pigment epithelium, choriod, and sclera were prepared. The vitreal surface of the retina in each eyecup was washed sequentially with 1% Triton X-100, water, and culture medium. This lysed the ganglion cells and neurons and glia of the inner nuclear layer, causing the retina to split apart within the inner nuclear layer. The damaged inner retina was peeled away, leaving photoreceptors attached to the pigment epithelium. The cell density of the inner nuclear layer was reduced 94% by this method, but there was little apparent damage to the photoreceptors. Lesioned eyecups produced normal melatonin levels in darkness at night, and melatonin production was inhibited by light. These results indicate that the inner retina is not necessary for melatonin production nor for regulation of photoreceptor melatonin synthesis by light. The lesion method used in this study may be useful for other physiological and biochemical studies of photoreceptors. PMID- 1586651 TI - Development of synapses in macaque monkey striate cortex. AB - A quantitative electron-microscopic (EM) analysis of the development of synaptic density (number of synapses/100 microns2 neuropil) has been done in primary visual cortex (striate, area 17) of the Old World monkey Macaca nemestrina. A comparative EM morphological study of developing synaptic contacts also was done in the same tissue. We find that a few immature synaptic contacts are present at fetal (F) 75 days either in the marginal zone, which becomes layer 1, or in the deepest portion of the cortical plate, the future layer 6. At F90-140 days synaptic contacts are found throughout the cortical plate, but their density remains higher in lower cortical layers. By F140 days synaptic density averaged for all layers (10.9) is three times higher than at F90 days. Just before and after birth, synaptic density rises very rapidly to peak at postnatal (P) 12 weeks (63) and then declines slowly to reach adult values (37.7) between 2-6 years. This pattern was further tested by comparing synaptic density in layer 2 which contains the last cells generated in the striate cortex to that in layer 6 which contains the first cells generated in the striate cortex. Layer 6 contained the first synapses, and had a higher density up to F140 days (an "inside-to outside" distribution). Synaptic density was equal in the two layers at F152 days and P2 days, but by P12 weeks synaptic density in layer 2 was 27% higher than that in layer 6 (an "outside-to-inside" distribution). After P12 weeks, the synaptic density declined 51% in layer 2 and 21% in layer 6 so that both layers achieved similar densities by P6 years. A light and EM comparison of neuropil and synaptic contact morphology finds that, at each age up to birth, synapses in layer 2 are generally less mature than those in layer 6, but these differences disappear shortly after birth. Between P6-24 weeks, synaptic contacts throughout the cortex acquire a mature morphology that clearly differentiates between asymmetric and symmetric types, although asymmetric contacts continue to acquire more postsynaptic density until adulthood. This complex developmental pattern suggests a sequence for synaptic developments which is more related to neuron birthdate than to the arrival of extrinsic pathways or developmental events occurring in specific laminae. PMID- 1586652 TI - Evidence of photoreceptor migration during early foveal development: a quantitative analysis of human fetal retinae. AB - We have analyzed aspects of photoreceptor topography in wholemounts of human fetal retinae in the age range 13-24 weeks of gestation. Fetal retinae were stained with cresyl violet and the sizes and packing densities of rods and cones analyzed in the conventional manner. Cones and rods were present within a differentiating region, free of mitotic figures and approximately centered on the putative fovea, represented by the foveal cone mosaic. At 13 weeks of gestation the foveal cone mosaic was clearly differentiated, cone nuclei reaching a packing density of 14,200 per mm2; a small number of rods were present in the immediately adjacent region. The packing densities of both rods and cones in these regions gradually increased and the area of the foveal cone mosaic gradually decreased throughout the age range sampled, although individual variations were evident. By 24 weeks of gestation, cone density was approximately 38,000 per mm2 in the foveal cone mosaic. The maximum rod density observed was 59,200 per mm2 in the region surrounding the foveal cone mosaic in a specimen of 20-21 weeks of gestation. In all specimens, maximum cone density occurred within the foveal cone mosaic and gradually declined towards the periphery of the differentiating region; a pronounced inverse relationship between cone soma diameter and packing density was also observed. The evidence strongly suggests that both rods and cones migrate centripetally, that is towards the center of the developing fovea, from early in development, possibly from the time that they first differentiate. The implications of these findings for foveal development are discussed. PMID- 1586653 TI - Neurotransmitter-specific identification and characterization of neurons in the all-cone retina of Anolis carolinensis, I: Gamma-aminobutyric acid. AB - The inhibitory amino-acid neurotransmitter, gamma-aminobutyric acid (GABA), was localized in the pure cone retina of the lizard Anolis carolinensis by autoradiographic and immunocytochemical techniques. Uptake of [3H]-GABA labeled horizontal cells, amacrine cells, numerous cells in the ganglion cell layer, both plexiform layers, and the nerve fiber layer. Label in the inner plexiform layer showed distinct lamination. The pattern of GABA immunoreactivity was similar to the pattern of [3H]-GABA uptake, although some differences, particularly in labeling of amacrine and ganglion cells, were observed. Immunocytochemistry revealed endogenous stores of GABA in a set of horizontal cells, amacrine cells, and cells in the ganglion cell layer. Both plexiform layers were labeled by the GABA antisera. Labeling in the inner plexiform layer (IPL) was highly stratified and GABA-immunoreactive strata were present in both sublaminae a and b. Six subtypes of conventionally placed GABA-immunoreactive amacrine cells and one displaced amacrine cell subtype were identified. Three of the six conventional amacrine cell subtypes were of pyriform morphology and three subtypes were of multipolar morphology. GABA-immunoreactive interstitial cells also were observed. Under certain conditions the GABA antiserum labeled the cones. Etching the resin eliminated cone labeling, suggesting that GABA in the cones is present in a labile pool, unlike GABA in horizontal or amacrine cells, or the observed labeling was not due to endogenous GABA. Cones did not demonstrate [3H]-GABA uptake. PMID- 1586654 TI - Binocular interactions in the cat's dorsal lateral geniculate nucleus, II: Effects on dominant-eye spatial-frequency and contrast processing. AB - The present study tested the hypothesis that nondominant-eye influences on lateral geniculate nucleus (LGN) neurons affect the processing of spatial and contrast information from the dominant eye. To do this, we determined the effects of stimulating the nondominant eye at its optimal spatial frequency on the responses of LGN cells to sine-wave gratings of different spatial frequency and contrast presented to the dominant eye. Detailed testing was carried out on 49 cells that had statistically significant responses to stimulation of the nondominant eye alone. Spatial-frequency response functions to nondominant-eye stimulation indicated that the responses were spatially tuned, as reported previously (Guido et al., 1989). Optimal spatial frequencies through the nondominant eye were significantly correlated with the optimal spatial frequencies through the dominant eye (r = 0.54; P less than 0.0001), and the optimal spatial frequencies were fairly similar for the two eyes. Nondominant-eye stimulation changed the maximal amplitude of the fundamental (F1) response to dominant-eye stimulation for only about 45% (22 of 49) of the cells that responded to nondominant-eye stimulation alone. The response vs. contrast function through the dominant eye was altered for 73% of the cells (51% independent of spatial frequency). Three types of effects were observed: a change in the initial slope of the response vs. contrast function (contrast gain), a change in the response amplitude at which saturation occurred, or an overall change in response at all contrasts. The incidence of these changes was similar for X and Y cells in LGN layers A, A1, and C (only four W cells were tested). Nondominant-eye stimulation had little or no effect on the sizes or sensitivities of the receptive-field centers or surrounds for the dominant eye. In addition, nondominant-eye stimulation had little or no effect on optimal spatial frequency, spatial resolution, or the bandwidth of spatial-frequency contrast sensitivity curves for the dominant eye. Possible functions of binocular interactions in the LGN are considered. The present results suggest a role in interocular contrast gain control. Interocular contrast differences can occur before the acquisition of binocular fusion, when the two eyes are viewing different aspects of a visual stimulus. Psychophysical and physiological studies suggest that an interocular mechanism exists to maintain relatively constant binocular interactions despite differences in interocular contrast. The present results suggest that at least part of this mechanism occurs in the LGN. PMID- 1586655 TI - N-methyl-D-aspartate-induced neurotoxicity in the adult rat retina. AB - The present study provides evidence that the adult mammalian retina is highly sensitive to the excitotoxic action of NMDA. In particular, we have investigated the effects of a single intravitreal injection of different doses of N-methyl-D aspartate (NMDA) (2-200 nmoles) on the adult rat retina. Morphological evaluation of transverse sections of retinae demonstrated a dose-dependent loss of cells in the ganglion cell layer (GCL) and a reduction in the thickness of the inner plexiform layer. No obvious alterations were noted in the more distal retinal layers. Quantitative analyses of Nissl-stained whole-mounted retinae revealed that administration of 20 nmoles of NMDA resulted in a 70% loss of cells with a soma diameter greater than 8 microns (presumed retinal ganglion cells); a 20% loss of cells with a soma diameter smaller than 8 microns (presumed displaced amacrine cells) was also observed. In addition, NMDA produced a dose-dependent decrease of retinal choline acetyltransferase (ChAT) activity, suggesting that NMDA affects cholinergic amacrine cells as well. MK-801, a non-competitive NMDA antagonist, completely prevented the NMDA-induced loss of cells in the GCL and blocked, in a dose-dependent manner, the NMDA-induced decrease of ChAT activity. The excitotoxic action of NMDA observed in these experiments is thus likely mediated through the NMDA receptor subtype. This "in vivo" model may be utilized to identify potential drugs that antagonize or limit the deleterious effects consequent to NMDA receptor overstimulation in the central nervous system. PMID- 1586656 TI - Visual effects of damage to P ganglion cells in macaques. AB - Four indices of visual performance were measured in control macaques and in macaques that had been exposed to monomeric acrylamide, a neurotoxicant that preferentially damages P retinal ganglion cells. Morphological examination of the retina and visual pathways of these monkeys showed virtually complete loss of P ganglion cells over a region extending to at least 40 deg from the fovea, and relative sparing of M ganglion cells. The four tests examined visual functions for which the visual pathway from P ganglion cells might be of great importance: visual acuity, contrast discrimination, hyperacuity, and shape discrimination. In the acrylamide-dosed monkeys, visual acuity was reduced slightly more than fourfold, a somewhat larger reduction than that seen previously after ibotenic acid lesions of the P pathway in the geniculate. The residual acuity was in good agreement with the Nyquist frequency calculated from the density of ON or OFF M ganglion cells. Contrast increment thresholds were elevated for the dosed monkeys only in one of the two conditions tested. The elevation was found only under those spatiotemporal conditions for which we have previously shown that contrast thresholds are increased by acrylamide exposure, and was most marked at low background contrasts. Vernier acuity was elevated in one dosed monkey, but not affected in a second monkey that also had severe loss of P ganglion cells. Finally, we found no effect of acrylamide exposure on the number of training trials required to learn simple or complex shape discriminations. These results support previous findings in showing that the P pathway mediates visual acuity, and they show that several other important aspects of visual perception are not exclusively dependent on the P pathway. PMID- 1586657 TI - Biomembranes. PMID- 1586658 TI - Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. AB - Efforts to overcome rapid uptake of liposomes by cells of the mononuclear phagocytic system (MPS) have identified that lipids derivatized with the hydrophilic polymer poly(ethylene glycol) (PEG) have many advantages. The structure-function relationship of PEG-derivatized phosphatidylethanolamine (PEG PE) has been examined by studies of blood lifetime and tissue distribution in both mice and rats. Liposomes composed of phosphatidylcholine (PC), cholesterol, and 7.5 mol% of PEG-PE show prolonged circulation and reduced MPS uptake when the PEG has a molecular weight in the range of 1000 to 5000. Up to 35% of the injected dose remains in the blood and less than 10% is taken up by the MPS (liver plus spleen) after 24 h in the best cases as compared to 1% and 40%, respectively, for liposomes without PEG-PE. Prolonged circulation with PEG-PE is independent of cholesterol, degree of saturation in either the PC or the PE lipid anchor, lipid dose, or addition of other negatively charged lipids, phosphatidylglycerol or cholesterol sulfate. This versatility in lipid composition and dose without alteration of blood lifetime or tissue distribution is essential for controlling drug dosage and release properties in a liposome based therapeutic agent. PMID- 1586659 TI - Transport and decarboxylation of liposomal phosphatidylserine: effect of cations. AB - Decarboxylation of liposomal phosphatidylserine by rat liver and Ehrlich ascites tumor mitochondria was taken as a measure of phospholipid transfer. The process was found to be greatly enhanced by the cytoplasmic fraction of rat liver containing nonspecific lipid transfer protein, but not by the cytoplasmic fraction from tumor cells. Divalent cations, like rat liver cytoplasmic fraction, also stimulated phosphatidylserine decarboxylation by facilitating the lipid association with mitochondria. In contrast, these cations, at 0.5-3 mM concentration, inhibited the cytoplasmic fraction-mediated phosphatidylserine transport. Monovalent cations were also inhibitory but at 20-150 mM concentration. However, they had no effect on phosphatidylserine decarboxylation in the absence of the cytoplasmic fraction. Further experiments with purified rat liver nonspecific lipid transfer protein and pyrene-labeled phosphatidylcholine and phosphatidylserine have shown that cations by neutralizing net negative charge on phospholipid donor vesicles decrease the interaction of protein with them and, in consequence, lower the rate of release of molecules to the water phase. PMID- 1586660 TI - The interaction of various cholesterol 'ancestors' with lipid membranes: a 2H-NMR study on oriented bilayers. AB - The effect of putative cholesterol 'precursors' on model membranes has been studied by deuterium nuclear, magnetic resonance (2H-NMR) spectroscopy. Oriented bilayers were prepared from 1-myristoyl-2-[2H27 myristoyl-sn-glycero-3 phosphocholine (DMPC-d27) and tricyclohexaprenols or octaprenediols. Order parameter profiles were determined and showed that tricyclohexaprenols and octaprenediols increase the acyl chain order in DMPC bilayers, but to a smaller extent than cholesterol. The order parameter increases, depending on the chain position, from 5% to 7% in the presence of ditertiary octaprenediol, and from 16% to 21% in the presence of tricyclohexaprenol-Z,Z. Aqueous multilamellar dispersions of DMPC-d27 and of DMPC-d27 containing 30 mol% tricyclohexaprenol-E,E were prepared, and the first moments calculated from 2H-NMR spectra over the temperature range 5-55 degrees C. Tricyclohexaprenol-E,E almost abolishes the phase transition of DMPC. Thus, as predicted, tricyclohexaprenols and octaprenediols have a cholesterol-like behaviour in lipid membranes; however their effect on the model DMPC system is weak. On the contrary, isoarborinol has no effect on the lipid chain order in the liquid-crystalline phase of DMPC bilayers. 2H-NMR spectra of aqueous dispersions of DMPC-d27 and 30 mol% isoarborinol between 25 and 60 degrees C showed the coexistence of two lamellar phases over a wide temperature range, which was confirmed by differential scanning calorimetry (DSC) and 31P-NMR spectroscopy. This absence of ordering effect of isoarborinol might be related to some inherent structural features. PMID- 1586661 TI - Interaction of alpha-tocopherol with fatty acids in membranes and ethanol. AB - The techniques of fluorescence polarization, ultraviolet light absorbance and fluorescence quenching by acrylamide are used to probe the structural role of alpha-tocopherol in phospholipid bilayers. Using 1,6-diphenyl-1,3,5-hexatriene (DPH) and a series of (anthroyloxy)stearic acid (AS) fluorescence probes, alpha tocopherol is shown to increase fluidity and decrease order of gel state bilayers, and to decrease fluidity and increase order of bilayers in the liquid crystalline state. More complex behavior is noted for bilayers made from mixed acyl chain phosphatidylcholines (PCs) where the sn-1 position is saturated and the sn-2 position unsaturated compared to bilayers composed of PCs where both acyl chains are either saturated or unsaturated. Complexation between alpha tocopherol and either free fatty acids or fatty acids esterified to the sn-2 position of PCs is indicated by ultraviolet light absorbance in both organic solution and in lipid bilayers. The strength of the complexes, expressed as interaction constants, are dependent upon the number of acyl chain unsaturations from 0 (stearic acid), to 6 (docosahexaenoic acid). Relation of the strength of these complexes to the degree of acyl chain unsaturation is confirmed by monitoring the fatty acid protection from acrylamide bleaching of alpha tocopherol. These experiments suggest that the extent of acrylamide bleaching is related to the extent of association with the fatty acids. PMID- 1586662 TI - Multiple conductance levels in rat heart inner mitochondrial membranes studied by patch clamping. AB - The behavior of the mitochondrial inner membrane multiple conductance channel (MCC) which has a peak conductance of 1-1.5 nS has been examined in rat heart mitochondria. MCC can display several unique characteristics: (a) prolonged open and closed times on the order of seconds to minutes, (b) a voltage dependence in which MCC opens (negative potential) or closes (positive potential) generally in steps, (c) a response to inhibitors such as amiodarone in steps corresponding at least approximately to those in (b), (d) a 'free-running mode' in which the current level rapidly fluctuates between a minimum of nine conductance levels but with a preferred occupation of the 0.5-0.7 nS levels, and (e) very large transitions (1-1.5 nS) resolved at 4 kHz bandwidth as single events with variable mean open time. PMID- 1586663 TI - Age-related thiamin transport by small intestinal microvillous vesicles of rat. AB - The effect of aging on the intestinal transport of thiamin was studied using small intestinal microvillous vesicles prepared from groups of rats aged 1, 2, 6, 12 and 24 months, respectively. The vesicles (enrichment 14.6-17.8-fold) were incubated with 0.125 to 12.5 microM tritiated thiamin and the radioactivity taken up was measured radiometrically after rapid filtration. The time course and cumulative uptake curves of thiamin and the inhibiting potency of the thiamin structural analogs pyrithiamin, amprolium and oxythiamin on the saturable component of thiamin transport were determined. The vesicle diameter was measured by using a computerized morphometric procedure, and found to be decreased in aged rats. The Km and Jmax values of the saturable component of transport increased with increasing age, the difference with younger groups being statistically significant at 24 and 12 months. The inhibitory potencies of pyrithiamin and amprolium gradually decreased with increasing age, while oxythiamin was devoid of significant inhibitory activity. Passive permeability coefficients decreased with increasing age, reaching their lowest value at 24 months. These results show that aging is associated with intrinsic alterations of the enterocytic plasma membrane resulting in a decrease of the affinity for thiamin, associated with a faster rate of the saturable component of thiamin transport, and with a significant depression of the non-saturable component. PMID- 1586664 TI - The influence of Mg2+ on anion binding to sarcoplasmic reticulum membranes as detected by 35Cl-NMR. AB - 35Cl-NMR spectroscopy has been used to study the competition between anions, including nucleotides, on skeletal muscle sarcoplasmic reticulum membranes. Different chloride binding sites can be distinguished according to their Mg2+ sensitivity. Phosphate binding is enhanced by Mg2+ whereas the anion transport inhibitor pyridoxalphosphate-6-azophenyl-2'-sulfonic acid (PPAPS) binding is not. The affinity of the enzyme for the Mg-adenylyl imidodiphosphate (MgAMP-PNP) complex is decreased whereas that for MgATP is increased. Three sets of binding sites can be discriminated from which chloride is displaced by different anions with varying efficiency. High affinity binding of AMP-PNP and PPAPS occurs at the same site, that can also be occupied by phosphate. Low-affinity binding of PPAPS and AMP-PNP also coincides, but in a site where phosphate binding is negligible. ATP and ADP bind to both sites. In the presence of Mg2+ a third anion binding site can be occupied by phosphate but neither by AMP-PNP nor PPAPS. PMID- 1586665 TI - Eicosatetraynoic and arachidonic acid-induced changes in cell membrane fluidity consonant with differences in computer-aided design-structures. AB - ETYA (5,8,11,14-eicosatetraynoic acid), a competitive analogue of arachidonic acid (AA), inhibits the proliferation of U937 (human monoblastoid) and PC3 (human prostate) cancer cells, without the overt cytotoxicity associated with AA at similar concentrations. The mechanism of inhibition is not established. ETYA at 100 microM acutely increased whole cell and isolated microsomal membrane fluidity of both cell lines to a greater extent than arachidonic acid. PC3 cells incubated with ETYA for 72 h evidenced increased membrane fluidity. This was measured by the fluorescence polarization parameter, R, using the probes TMA-DPH and DPH for whole cell and isolated membrane fractions, respectively. Compared with whole cells, isolated membranes yielded a 10-20-fold increase in fluorescence intensity. The intramolecular conformational profiles of both ETYA and AA were explored using a combination of molecular mechanics energy minimization and molecular dynamics simulation. While it is possible that not all of the low energy conformational states of either molecule were sampled, the large number of low-energy conformers determined for ETYA correspond to kink deformed conformers relative to the family of AA conformers. These kinks make the molecular cross sections of ETYA larger than AA and arise from the four alkyne bond geometries. This structural finding is consistent with ETYA's greater effect on membrane fluidity. Dissociation between the extent of change in membrane fluidity due to ETYA or AA and inhibition of DNA synthesis can suggest that either (A) increased fluidity and inhibition of DNA synthesis are independent, or as we believe more likely, (B) greater membrane fluidity evoked by ETYA is important for inhibiting DNA synthesis, while changes induced by AA are insufficient or differ qualitatively from those required to initiate and sustain these nonlethal events. PMID- 1586666 TI - Down-regulation and recycling of the nitrobenzylthioinosine-sensitive nucleoside transporter in cultured chromaffin cells. AB - The dynamics of the nitrobenzylthioinosine (NBTI)-sensitive nucleoside transporter were studied in cultured chromaffin cells. Photolabelling of transporters with [3H]NBTI induced a down-regulation of this protein from the plasma membrane with a half-life value of 2.31 +/- 0.61 h, measured by specific isolation of plasma membrane on polycationic beads. In this internalization step 50-60% of transporters were destroyed. The remaining labelled protein reappeared in plasma membranes and underwent a new disappearance cycle with a longer half life period (34.65 +/- 3.9 h). A similar pattern of internalization and reappearance of nucleoside transporters was observed in cells cross-linked with non-labelled NBTI, with a half value of reappearance of 33 h. Chromaffin cells cultured in the presence of the protein synthesis inhibitor, cycloheximide, had a component of disappearance for NBTI binding sites with a half-life value of 24.6 +/- 1.4 h. PMID- 1586667 TI - The volume changes associated with the operation of the 'simple' transporter. AB - The effects of hydrostatic pressure (0.1-50 MPa) on uridine transport mediated by the 'simple' facilitated nucleoside transporter of guinea-pig and human erythrocytes have been studied in an attempt to identify the volume changes which occur during transport. Pressure inhibited the zero-trans (influx or efflux) mode of uridine transport in guinea-pig cells significantly more (about 2.2- x) than equilibrium exchange. The equilibrium binding of 3H-nitrobenzylthioinosine, a potent specific inhibitor of nucleoside transport, to human red cells and ghosts, was not significantly altered by pressure suggesting that the permeation site was unperturbed. Thus pressure inhibited the transporter primarily by preventing the volume increase associated with the translocation step. Furthermore, the return of the 'empty' transporter was found to be rate-limiting because it required a larger increase in volume than when the transporter was loaded with substrate. PMID- 1586668 TI - Induction of Ca2+ transport in liposomes by insulin. AB - The requirement of extracellular Ca2+ for insulin action has been indicated by past studies. With a view to understand the interaction of insulin with Ca2+ in the vicinity of the cell membrane, we have examined the ability of insulin and its constituent polypeptide chains A and B to translocate Ca2+ and Mg2+ across the lipid bilayer in two sets of synthetic liposomes. The first were unilamellar vesicles made of dimyristoylphosphatidylcholine and contained the Ca2+ sensor dye arsenazo III. Peptide-mediated Ca2+ and Mg2+ transport in these vesicles was monitored at 37 degrees C in a neutral buffer containing CaCl2 or MgCl2 using a difference absorbance method. In the second set, multilamellar vesicles of egg lecithin containing trapped fura-2 were employed and the cation transport was followed at 20 degrees C by fluorescence changes in the dye. Control experiments indicated that the hormonal peptides caused no appreciable perturbation of the vesicles leading to leakage of contents or membrane fusion. In both liposome systems, substantial Ca2+ and Mg2+ transport was observed with insulin and the B chain; the A chain was less effective as an ionophore. Quantitative analysis of the transport kinetic data on the B chain showed a 1:1 peptide-Ca2+ complex formed inside the membrane. In light of the available structural data on Ca2+ binding by insulin and insulin receptor, our results suggest the possibility of the hormone interacting with the receptor with the bound Ca2+. PMID- 1586669 TI - Phospholipid-dependence of rat liver plasma membrane protein kinase activities--a new approach. AB - The influence of the phospholipid composition and fluidity on protein kinase A and protein kinase C activities in rat liver plasma membranes was studied. We observed that enrichment of membranes with phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine and dioleoylphosphatidylcholine caused activation of both protein kinases. Phosphatidylglycerol was found to be most effective activator. The enrichment of plasma membranes with dipalmitoylphosphatidylcholine and sphingomyelin led to decrease in protein kinase A and C activities. The stimulatory effect of phosphatidylglycerol was confirmed in plasma membranes pretreated with exogenous phospholipases A2, C and D, and subsequently enriched with phosphatidylglycerol. We suggest that besides the specific presence of definite phospholipids protein kinases A and C require a more fluid membrane lipid bilayer to display an optimal activity. PMID- 1586670 TI - Singlet oxygen production and fluorescence yields of merocyanine 540: a comparative study in solution and model membrane systems. AB - Singlet oxygen and fluorescence quantum yields of merocyanine 540 were measured in solution (methanol, ethanol, n-heptanol) and in model membrane systems (cationic micelles, unilamellar dimyristoyl- and dipalmitoylphosphatidylcholine vesicles). Both singlet oxygen quantum yields and fluorescence quantum yields increase with increasing viscosity/rigidity of the surrounding medium: the yield of singlet oxygen production (24 degrees C) goes from 0.002 in methanol to 0.04 in dipalmitoylphosphatidylcholine vesicles, and fluorescence yields (25 degrees C) change from 0.14 to 0.61 in the same media. The data are consistent with previous findings that photoisomerization is in direct competition with intersystem crossing and radiative relaxation. Therefore, a singlet oxygen yield close to the maximum value of 0.11 can only be achieved after both photoisomerization and internal conversion are prevented by a highly viscous environment. PMID- 1586671 TI - A mathematical analysis of the force-stiffness characteristics of muscles in control of a single joint system. AB - Feldman (1966) has proposed that a muscle endowed with its spinal reflex system behaves as a non-linear spring with an adjustable resting length. In contrast, because of the length-tension properties of muscles, many researchers have modeled them as non-linear springs with adjustable stiffness. Here we test the merits of each approach: Initially, it is proven that the adjustable stiffness model predicts that isometric muscle force and stiffness are linearly related. We show that this prediction is not supported by data on the static stiffness-force characteristics of reflexive muscles, where stiffness grows non-linearly with force. Therefore, an intact muscle-reflex system does not behave as a non-linear spring with an adjustable stiffness. However, when the same muscle is devoid of its reflexes, the data shows that stiffness grows linearly with force. We aim to understand the functional advantage of the non-linear stiffness-force relationship present in the reflexive muscle. Control of an inverted pendulum with a pair of antagonist muscles is considered. Using an active-state muscle model we describe force development in an areflexive muscle. From the data on the relationship of stiffness and force in the intact muscle we derive the length tension properties of a reflexive muscle. It is shown that a muscle under the control of its spinal reflexes resembles a non-linear spring with an adjustable resting length. This provides independent evidence in support of the Feldman hypothesis of an adjustable resting length as the control parameter of a reflexive muscle, but it disagrees with his particular formulation. In order to maintain stability of the single joint system, we prove that a necessary condition is that muscle stiffness must grow at least linearly with force at isometric conditions. This shows that co-contraction of antagonist muscles may actually destabilize the limb if the slope of this stiffness-force relationship is less than an amount specified by the change in the moment arm of the muscle as a function of joint configuration. In a reflexive muscle where stiffness grows faster than linearly with force, co-contraction will always lead to an increase in stiffness. Furthermore, with the reflexive muscles, the same level of joint stiffness can be produced by much smaller muscle forces because of the non-linear stiffness-force relationship. This allows the joint to remain stable at a fraction of the metabolic energy cost associated with maintaining stability with areflexive muscles. PMID- 1586672 TI - Analyzing the dynamics of hand tremor time series. AB - We investigate physiological, essential and parkinsonian hand tremor measured by the acceleration of the stretched hand. Methods from the theory of dynamical systems and from stochastics are used. It turns out that the physiological tremor can be described as a linear stochastic process, and that the parkinsonian tremor is nonlinear and deterministic, even chaotic. The essential tremor adopts a middle position, it is nonlinear and stochastic. PMID- 1586673 TI - Artificial neural network classification of Drosophila courtship song mutants. AB - Courtship songs produced by Drosophila males--wild-type, plus the cacophony and dissonance behavioral mutants--were examined with the aid of newly developed strategies for adaptive acoustic analysis and classification. This system used several techniques involving artificial neural networks (a.k.a. parallel distributed processing), including learned vector quantization of signals and non linear adaption (back-propagation) of data analysis. "Pulse" song from several individual wild-type and mutant males were first vector-quantized according to their frequency spectra. The accumulated quantized data of this kind, for a given song, were then used to "teach" or adapt a multiple-layered feedforward artificial neural network, which classified that song according to its original genotype. Results are presented on the performance of the final adapted system when faced with novel test data and on acoustic features the system decides upon for predicting the song-mutant genotype in question. The potential applications and extensions of this new system are discussed, including how it could be used to screen for courtship mutants, search novel behavior patterns or cause-and effect relationships associated with reproduction, compress these kinds of data for digital storage, and analyze Drosophila behavior beyond the case of courtship song. PMID- 1586674 TI - Local optimization of neuron arbors. AB - How parsimoniously is brain wiring laid out, that is, how well does a neuron minimize costs of connections among its synapses? Neural optimization of dendritic and axonic arbors can be evaluated using a generalization of the Steiner tree concept from combinatorial network optimization theory. Local branch junction geometry of neuronal connecting structures fits a volume minimization model well. In addition, volume of the arborizations at this neighborhood level is significantly more strongly minimized than their length, signal propagation speed, or surface area. The mechanism of this local volume optimization resembles those involved in formation of nonliving tree structures such as river junctions and electric-discharge patterns, and appears to govern initial nerve growth-cone behavior through vector-mechanical energy minimization. PMID- 1586675 TI - Dual stable point model of muscle activation and deactivation. AB - Two dynamic models of muscle activation and deactivation based on the concepts of ion transport, reaction rates, and muscle mechanics are proposed. Storage release and uptake of calcium by the sarcoplasmic reticulum, and a two-step chemical reaction of calcium and troponin are included in the first model. This is a concise version of the complex chemical reactions of muscle activation and deactivation in sarcoplasm. The second model is similar to the first, but calcium troponin reactions are simplified into two nonlinear rates functions. Due to these nonlinear dynamics, the second model can explain the catch-like enhancement of isometric force response. Simulation results which match experimental data are shown. Also, two new phenomena which need further experiment to verify are predicted by the second model. PMID- 1586676 TI - Digital filters for firing rate estimation. AB - When a rate histogram is used to represent the firing pattern of a neuron there is the potential for serious error due to aliasing, and because of this the rate histogram is a very poor way to represent neural activity. It is theoretically possible to encode a signal in a spike train and decode it without error by filtering and sampling. There is no natural optimal filter design for this problem, but it is possible to specify the characteristics of a good rate estimating filter heuristically and design a filter with these characteristics. Two rate estimating filters are described here. Their performance has been tested, and compared to the rate histogram and the French-Holden rate estimating algorithm, by measuring their ability to recover signals encoded as impulse sequences by Integral Pulse Frequency Modulation (IPFM). These filters are simple to implement and perform well. They should be used in preference to the rate histogram. PMID- 1586677 TI - Evaluation of some nonrecursive digital filters for signals of auditory evoked responses. AB - Auditory brain stem evoked responses are routinely used in audiology and otoneurology. Because recordings include more or less noise, the signals of evoked responses need digital filtering to suppress the noise. Nonrecursive digital filters are often the best since they can be organized to have no phase shift, which is essential in order not to distort sensitive parameters, as latency, in evoked responses. We have studied effects of some nonrecursive digital filters on the latency parameters of evoked responses. It turned out that digital filtering can have considerable influence on latencies, and thus the choice of appropriate filters is crucial. PMID- 1586678 TI - Analytical reconstruction of the neuronal input current from spike train data. AB - The time course of the current driving action potential generation at a neuron investigated experimentally is in general not measurable directly. In this paper an indirect method is introduced that allows estimation of this unknown current time course using only spike train data. Assuming the leaky integrator model as valid for the action potential encoding site of the investigated neuron, the unknown input current is obtained by determining (analytically) a current time course that upon injection into the leaky integrator model evokes action potential sequences identical to those observed experimentally. Applications of this current-reconstruction procedure to neuronal output data obtained from a leaky integrator model showed that the procedure allows a good estimation of the underlying input current even if the membrane time constant of the investigated neuron is not known exactly. Additionally, an application of current reconstruction to experimental data obtained from a cat muscle spindle primary afferent subject to repeated gamma-stimuli is demonstrated. PMID- 1586679 TI - Free radicals in peritoneal dialysis: agents of damage? PMID- 1586680 TI - Towards tailored dialysis fluids in CAPD--the role of reduced calcium and magnesium in dialysis fluids. PMID- 1586681 TI - Red blood cell susceptibility to lipid peroxidation, membrane lipid composition, and antioxidant enzymes in continuous ambulatory peritoneal dialysis patients. AB - OBJECTIVE: To investigate the overall susceptibility of red blood cells (RBC) to lipid peroxidation from patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: The following parameters were measured: RBC malondialdehyde (MDA) production after oxidative stress with H2O2, RBC antioxidant enzymes glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and RBC membrane lipid composition. The levels of plasma vitamin E and serum selenium were also assayed. PATIENTS: Eleven patients on continuous ambulatory peritoneal dialysis. Twenty-one healthy blood donors of similar age were used as normal controls. RESULTS: The MDA formation after H2O2 stimulation was normal in CAPD patients (0.79 +/- 0.1 mumol/gHb versus 0.78 +/- 0.1 in the control group). RBC from CAPD patients also showed a normal SOD activity, a more than adequate vitamin E status, and a peculiar pattern of membrane lipids, with reduced polyunsaturated fatty acids (p less than 0.001) and increased monounsaturated fatty acids (p less than 0.001). Both RBC GSH-Px activity, a selenium-dependent enzyme, and serum selenium levels were significantly lower in CAPD patients, and a significant positive correlation (r = 0.68; p less than 0.02) between the two parameters was found. CONCLUSIONS: This study found a normal sensitivity to oxidant stress in RBC from a group of CAPD patients, despite an impaired GSH-Px activity. The peculiar lipid pattern of RBC membrane, characterized by reduced PUFA and increased MUFA content, may contribute, in addition to adequate SOD activity and vitamin E status, to normal RBC lipid peroxidation. PMID- 1586682 TI - Management of refractory peritonitis to maintain the peritoneum for subsequent dialysis. AB - Peritonitis and its sequelae remain major clinical problems in treating peritoneal dialysis (PD) patients. One of these sequelae is the formation of intra-abdominal adhesions, preventing a patient from returning to peritoneal dialysis after a Tenckhoff catheter is removed for refractory peritonitis. We have recently applied a technique that appears to reduce the incidence of this severe complication. When it is determined that a catheter will be removed for refractory peritonitis, hourly peritoneal dialysis exchanges are performed for 12 hr prior to surgery. Postoperatively, the abdomen is rested for 48 hr, after which a temporary peritoneal dialysis catheter is placed at the bedside and hourly exchanges (with antibiotics) are performed for 2-3 days or until the dialysis fluid white blood cell count improves. Then the temporary catheter is removed and the abdomen is rested until the Tenckhoff catheter is replaced in 10 14 days. We treated 5 consecutive patients with refractory peritonitis (2 Pseudomonas, 1 Proteus, 1 Candida, 1 S. aureus) with this technique. All 5 patients were able to return successfully to peritoneal dialysis. At our institution over the past five years, 9 patients with refractory peritonitis due to the same organisms have had their catheters removed. Only 5 (56%) were able to return to PD. Although preliminary, our technique holds promise for those patients wishing to return to peritoneal dialysis after having a catheter removed for refractory peritonitis. PMID- 1586683 TI - Streptococcus peritonitis with urticaria. AB - Peritonitis following urticaria on two occasions in a 46-year-old white female treated with CAPD for nine years is reported. On both occasions an episode of urticaria and pruritus occurred 24 hr before the dialysate became cloudy, and the patient experienced abdominal pain, nausea, and vomiting. The culture of the peritoneal dialysis effluent grew gamma Streptococcus with the first episode. To our knowledge this is the first report of CAPD peritonitis preceded by urticaria where the skin findings were most likely related to the peritoneal infection. PMID- 1586684 TI - Randomized study of peritonitis with conventional versus O-set techniques in continuous ambulatory peritoneal dialysis. AB - We performed a prospective randomized trial, comparing the incidence of peritonitis between a flush-disconnect (O-System, Baxter, Deerfield, IL) (OS) and a conventional (System II, Baxter) (CS) continuous ambulatory peritoneal dialysis (CAPD) method. Sixty consenting patients with no significant physical disabilities who commenced CAPD after May 1987 were entered and followed for a minimum of 12 months. Thirty were placed on the OS system and 30 were placed on CS. Age, gender, and time for training did not differ significantly. The period of observation for OS was 375 months; CS was observed for 430 months. OS patients experienced 28 episodes of peritonitis (13.4 months/patient/episode) compared with 88 (4.9 months/patient/episode) in CS (p less than 0.005). By 6 months, 32% of OS patients had had at least one episode of peritonitis, compared with 62% of CS patients; at 12 months, these figures rose to 48% for OS and 91% for CS (p less than 0.01) patients (Life Table Analysis). The median survival time to first peritonitis episode was 5.1 months in CS and 9.7 months in OS (p less than 0.01). Exit-site infections occurred in 14/30 (46%) of patients on OS and in 13/30 (43%) of CS patients. We conclude that the OS was associated with a significant reduction in the incidence of peritonitis. PMID- 1586685 TI - Dialysis efficiency in continuous ambulatory peritoneal dialysis patients treated with erythropoietin. AB - OBJECTIVE: To determine the effect of subcutaneous erythropoietin treatment on dialysis efficiency in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Dialysis efficiency, platelet and white cell aggregation, and red cell deformability were measured monthly for six months in nine anaemic CAPD patients treated with erythropoietin, and on a single occasion in seven control CAPD patients with intrinsically high haemoglobin concentrations. SETTING: Renal dialysis unit. PATIENTS: Nine patients stable on CAPD for a minimum of six months and with haemoglobin concentrations less than 8.5 g/dl were treated with erythropoietin. Seven CAPD patients matched for age and renal function, with haemoglobins greater than 9.0 g/dl served as controls. RESULTS: Daily peritoneal clearances and net ultrafiltration volumes were unchanged when haematocrit increased from 25.0 +/- 2.2% to 36.5 +/- 3.5%. Spontaneous whole blood platelet aggregation was significantly increased from week twelve (pre-treatment aggregation 46 +/- 23%; 12 weeks: 67 +/- 19%, p less than 0.05; 16 weeks: 64 +/- 19%, p less than 0.01; 20 weeks: 71 +/- 16%, p less than 0.01; 24 weeks: 73 +/- 10%, p less than 0.01). CONCLUSIONS: The increase in haematocrit and platelet aggregation associated with erythropoietin treatment did not affect peritoneal clearances or ultrafiltration capacity. PMID- 1586686 TI - Continuous ambulatory peritoneal dialysis after abdominal aortic graft surgery. PMID- 1586687 TI - The effect of hemoglobin concentration on peritoneal mass transfer and drain volumes in continuous ambulatory peritoneal dialysis. AB - OBJECTIVE: To determine whether a correlation exists between hemoglobin levels and peritoneal mass transfer or drain volumes in continuous ambulatory peritoneal dialysis (CAPD) patients. DESIGN: Prospective study of two groups of CAPD patients, identified on the basis of their stable hemoglobin levels. Group A- hemoglobin less than 8.5 g/dL; Group B--hemoglobin greater than 10.5 g/dL. Peritoneal mass transfer and drain volumes were measured for each patient, after which a subgroup of Group A was treated with rHuEPO (forming Group C) and measurements repeated once hemoglobin had risen by at least 2.0 g/dL. SETTING: Single renal unit of a university teaching hospital. PATIENTS: Twenty-seven patients established on CAPD, selected according to their stable hemoglobin level. Group A--14 patients; Group B--13 patients; Group C (subgroup of A)--8 patients. MAIN OUTCOME MEASURES: Difference between peritoneal mass transfer or drain volume in Group A versus Group B, and in Group C before and after rHuEPO therapy. Serum biochemical parameters in Group C before and after rHuEPO therapy. RESULTS: No statistically significant differences in any of the parameters measured were found between groups A and B, or before and after rHuEPO therapy in Group C. CONCLUSIONS: Peritoneal transfer of small solutes and water is not influenced by hemoglobin level, and does not change following otherwise effective treatment with rHuEPO. PMID- 1586688 TI - Effect of peritoneal macrophages from intermittent peritoneal dialysis patients on lymphocytes in culture. AB - To investigate the biological activity of peritoneal macrophages, cells isolated from dialysate of 30 patients with end-stage kidney disease treated by intermittent peritoneal dialysis and from ascites of 6 patients with cardiac insufficiency (relative control group) were added to autologous, phytohemagglutinin (PHA)-stimulated lymphocyte cultures. Macrophages of dialyzed patients induced a dose-dependent increase in autologous lymphocyte proliferation, whereas macrophages obtained from control subjects exerted a suppressive effect on those cultures. The enhanced lymphocyte proliferation by macrophages from dialyzed patients was corroborated by the increased metabolic activity of macrophages as evaluated by the increased nitro blue tetrazolium (NBT) reduction test and increased functional expression of Fc receptors (FcR). The subpopulation of macrophages from patients with HLA-DR antigens as determined by HB55 monoclonal antibody, inhibited lymphoproliferation in vitro. We conclude that peritoneal macrophages from dialyzed patients represent a heterogenous population of cells with different phenotypic and functional characteristics. PMID- 1586689 TI - Continuous ambulatory peritoneal dialysis and renal transplantation: a ten-year experience in a single center. AB - OBJECTIVE: To assess whether a renal graft outcome is dependent on the modality of dialysis prior to transplantation and to assess risk of peritonitis and catheter-related problems posttransplantation. DESIGN: Retrospect analysis of the outcome of a first cadaveric renal transplantation from hemodialysis (HD) and CAPD patients over a ten-year period. PATIENTS: Out of a total of 905 renal transplants over a ten-year period, 699 were first grafts; 500 of these (241 on CAPD, 259 on hemodialysis) were analyzed while the remaining (incomplete data, predialysis, pediatric) were assessed for graft and patient survival only. MAIN OUTCOME: Graft and patient survival cases were identical in the two groups (five year graft survival: CAPD 67%, hemodialysis 66%; five-year patient survival: CAPD 88%, hemodialysis 87%). CAPD posttransplant was necessary in 37 patients, while 10 developed peritonitis mostly related to CAPD use and responded to appropriate therapy. Routine catheter removal posttransplant was undertaken between 8 and 12 weeks. CONCLUSION: Excellent graft and patient survival is achieved independent of the modality of dialysis prior to transplantation. Peritoneal dialysis can be used postgrafting, but there is a risk of peritonitis, which can be successfully managed with antibiotics and catheter removal. Great care is needed in executing the dialysis and catheter care after transplantation. PMID- 1586690 TI - Lipid peroxidation and antioxidants in continuous ambulatory dialysis patients. AB - OBJECTIVE: Oxidative cell damage due to the production of free radical species has been implicated in the pathogenesis of cardiovascular disease for which dialysis patients are at increased risk. Plasma lipid peroxides (malon dialdehyde), the antioxidants plasma albumin thiol, and red cell superoxide dismutase (SOD) were therefore measured in 18 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), 20 hemodialysis patients, and 30 normal controls. SETTING: Renal dialysis unit. RESULTS: Malondialdehyde (MDA) concentrations were significantly higher in dialysis patients compared to controls (p less than 0.001) and were significantly higher in CAPD patients compared to hemodialysis patients, p less than 0.001 (CAPD, median and range: 11.25 (8.4-15.5) nmol/mL; hemodialysis: 8.75 (7.0-12.6) nmol/mL; controls: 6.65 (5.2-9.6) nmol/mL). Plasma thiol and red cell SOD were significantly lower in dialysis patients compared to controls, but there was no significant difference between CAPD and hemodialysis patients (CAPD thiol: 333.5 (282-480) mumol/L; hemodialysis thiol: 344 (203-468) mumol/L; control thiol: 421.5 (351-504) mumol/L; CAPD SOD: 78.2 (42.4-112.8) u/1/2 mL red cells; hemodialysis SOD: 89.4 (44.6-121.1) u/1/2 mL red cells; control SOD: 96.8 (66.8-153.4) u/1/2 mL red cells). Red cell SOD was significantly negatively correlated with duration of dialysis in CAPD patients (r = -0.683, p less than 0.01). CONCLUSION: In dialysis patients there is indirect evidence for increased free radical activity, which may be further influenced by the mode of dialysis. PMID- 1586691 TI - Peritoneal dialysis catheter obstruction by a fallopian tube: a case report. PMID- 1586692 TI - Peritoneal dialysis in the presence of a stoma. PMID- 1586693 TI - Residual peritoneal volumes by CT scanning in CAPD patients. PMID- 1586695 TI - Savings with the use of the "twin bag". PMID- 1586694 TI - Peritoneal plasminogen activator activity after chronic exposure to dialysis fluid. PMID- 1586696 TI - Intraperitoneal erythromycin for diabetic gastroparesis in CAPD. PMID- 1586697 TI - CAPD drainage failure due to Tenckhoff catheter fracture: a case report. PMID- 1586698 TI - Initial experience with CAPD in patients with HIV infection in a developing country. PMID- 1586699 TI - A new case of peritonitis due to Campylobacter jejuni in CAPD. PMID- 1586700 TI - Literature. April--June 1992. PMID- 1586701 TI - IL-5-induced IgA synthesis by LPS-stimulated mouse B cells is prevented by protein kinase C inhibitors. AB - We have previously demonstrated that activation of protein kinase C (PKC) by phorbol esters induces selectively IgA synthesis by mouse B cells. In this study, we investigated the effects of a number of protein kinase inhibitors on IgA secretion induced by a recombinant murine IL-5 in LPS-stimulated mouse B cells. The results show that PKC inhibitors, such as sphingosine (SPH), staurosporine (STP) and H-7, blocked IL-5-induced IgA synthesis; the protein kinase A inhibitor HA-1004 and the inhibitor of calcium/calmodulin dependent protein kinase W-7 had no effect on IgA secretion induced by IL-5. The proliferation of the IL-5 sensitive B13 cell line in response to IL-5 was also inhibited by addition of SPH or STP or H-7. The data suggest an involvement of the PKC pathway in IL-5-induced B cell differentiation into IgA secreting cells. PMID- 1586702 TI - A comparison of assays for the response of primary human T-cells upon stimulation with interleukin-2, interleukin-4 and interleukin-7. AB - The most commonly used assay to quantitate the response of peripheral T-cells upon stimulation with growth factors is determination of incorporated [3H]TdR. We compared this test to three other methods: 1. direct counting of cells with a Coulter type counter as reference assay, 2. a colorimetric assay using the tetrazolium dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium (MTT), which is a cheap and increasingly popular non-radioactive method and 3. incorporation of the thymidine analog 5-bromo-2'-deoxyuridine detection with a monoclonal antibody on cytospins. Primary human PHA-blasts from greater than 30 healthy individuals were stimulated with IL-2, IL-4 and IL-7 and assayed with up to four different methods. We discuss the advantages and disadvantages of the assays used and the effects of differences between cell preparations. We observed no significant variations between individuals for the dose dependence, but the relative efficiency of IL-4 compared to IL-2 and IL-7 was variable. This was probably due to the slower response observed upon stimulation with this factor. PMID- 1586703 TI - Molecular genetics of von Willebrand disease. PMID- 1586704 TI - Translocations involving band 3q27 and Ig gene regions in non-Hodgkin's lymphoma. AB - We report a series of 20 non-Hodgkin's lymphomas (NHL) in which cytogenetic analysis showed a translocation involving band 3q27 and the site of one of the three Ig genes (14q32, 2p12, 22q11) in the neoplastic cells. These cases were found in a series of 319 patients with clonal chromosomal abnormalities studied over a 7-year period. Fourteen patients had diffuse lymphoma, mainly of large cell type and the remaining six were follicular lymphomas. All cases studied were of B-cell phenotype. A t(3;14)(q27;q32) was commonest, found in 15 patients (4.7%), with the two variant translocations, t(3;22)(q27;q11) and t(2;3)(p12;q27), being found in three and two patients, respectively. Additional chromosomal defects were present in most patients, but two patients had this type of translocation as the sole abnormality. These results indicate that translocations involving band 3q27 and Ig genes are not uncommon, and suggest that a novel oncogene, located at band 3q27, may be implicated in B-cell NHL. PMID- 1586705 TI - Interferon-gamma gene expression in unstimulated bone marrow mononuclear cells predicts a good response to cyclosporine therapy in aplastic anemia. AB - Cyclosporine (CyA) therapy has been shown to be effective in some patients with aplastic anemia. In an attempt to characterize aplastic patients likely to benefit from CyA therapy, we examined bone marrow mononuclear cells (BMMC) obtained before therapy from 23 patients with aplastic anemia, who were treated with CyA alone. Expression of four myelosuppressive cytokines, including tumor necrosis factor (TNF), lymphotoxin, macrophage inflammatory protein-1 alpha (MIP 1 alpha), and interferon-gamma (IFN-gamma) was examined using polymerase chain reaction (PCR)-assisted messenger RNA (mRNA) amplification. mRNA for TNF, lymphotoxin, and MIP-1 alpha was readily detectable at variable levels in BMMC from normal and transfused controls as well as in BMMC from aplastic patients. In contrast, IFN-gamma mRNA was only demonstrable in BMMC from some patients with aplastic anemia, irrespective of a history of transfusions. Of 13 patients who responded to CyA therapy and achieved transfusion-independence, IFN-gamma mRNA was detected in 12 patients, whereas the mRNA was only detectable in 3 of 10 patients refractory to CyA therapy (P = .003, Fisher's exact test). Follow-up examination of BMMC obtained from seven CyA-responding patients after hematologic remission showed disappearance of IFN-gamma mRNA in four patients. These results suggest that detection of IFN-gamma gene expression in pretreatment BMMC from aplastic patients using PCR may be helpful in predicting a good response to CyA therapy. PMID- 1586706 TI - Multicenter randomized study comparing cyclosporine-A alone and antithymocyte globulin with prednisone for treatment of severe aplastic anemia. AB - We report the results of a randomized multicenter study comparing the efficacy of antithymocyte globulin (ATG) with that of cyclosporin A (CsA) as first-line therapy for severe aplastic anemia (SAA). Patients were randomized to receive ATG and prednisone (PDN) or CsA; hematologic response and toxicity were compared. At 3-month evaluation, patients who had no or minimal response received the alternative therapy to assess the value of a sequential immunosuppressive therapy for treatment of severe aplastic anemia. One hundred nineteen patients were randomized; 25 were excluded, of whom 3 were misdiagnosed and 22 did not follow the cross-over protocol. Ninety-four patients were analyzed; 46 received CsA, and 48 received ATG-PDN. The actuarial survival was 66.7%, with a median follow-up time of 19 months. There was no significant difference in survival between the groups with, at 3 months, an actuarial survival of 88% in the CsA group and 75% in the ATG group (NS); at 12 months, it was 70% in the CsA group and 64% in the ATG group (NS). The percentage of complete and partial response was 11.6% and 16%, respectively, at 3 months, and 31.6% and 30%, respectively, at 12 months (NS). The main prognostic factor was the absolute neutrophil count (ANC) at entry: Patients with ANC less than 0.2 x 10(9)/L had a significantly lower survival as compared with patients with more than 0.2 x 10(9)/L ANC (P = .0001). At 12 months, 62 evaluable patients were alive, with a complete or partial response in 36 patients. Patients who had responded to the first treatment had a better recovery of bone marrow failure than those who had sequential immunosuppression. The main complication was infection, which was more often observed and more often lethal during ATG and PDN therapy. In this study, initial treatment of SAA with either CsA or ATG-PDN followed by cross-over therapy for nonresponders produced comparable response and survival rates. PMID- 1586707 TI - Phase I trial of an interleukin-2 (IL-2) fusion toxin (DAB486IL-2) in hematologic malignancies expressing the IL-2 receptor. AB - DAB486IL-2 is a recombinant fusion toxin in which the native receptor binding domain of diphtheria toxin has been replaced with human interleukin-2 (IL-2). It selectively binds and intoxicates only cells that bear the high-affinity receptor for IL-2. In the first clinical trial of a genetically engineered ligand fusion toxin, we have treated 18 patients with chemotherapy-resistant IL-2 receptor expressing hematologic malignancies with escalating doses of DAB486IL-2. The maximal tolerated dose of a daily intravenous bolus of DAB486IL-2 was 0.1 mg/kg per day for 10 doses, established by asymptomatic, reversible elevations of hepatic transaminases without changes in other tests of liver function. Other mild reversible side effects noted were rash, nausea, elevated creatinine, chest tightness, and fever. Pharmacokinetic analysis showed a monophasic clearance of 5.8 +/- 0.7 minutes with peak levels of 3,549 +/- 1,041 mg/mL at the 0.1 mg/kg dose. Approximately 50% of patients developed an antibody response to diphtheria toxin or DAB486IL-2. The presence of such antibodies did not preclude patients from experiencing an antitumor response as four of the six patients with antitumor effect had detectable antibody titers. Although this was a phase I trial designed to define the safety of DAB486IL-2, remissions were observed in three patients lasting from 5 to over 18 months. The ability to achieve significant tumor reductions in this group of heavily treated patients is encouraging and suggests additional trials are warranted in hematologic malignancies. PMID- 1586708 TI - Immunosuppressive therapy of aplastic anemia: results of a prospective, randomized trial of antithymocyte globulin (ATG), methylprednisolone, and oxymetholone to ATG, very high-dose methylprednisolone, and oxymetholone. AB - Sixty-eight patients with moderate (n = 15) or severe (n = 53) aplastic anemia were entered into a prospective, randomized, two-arm treatment study comparing antihuman thymocyte globulin (ATG), lower-dose methylprednisolone (LDM) and oxymetholone to ATG, higher-dose methylprednisolone (HDM), and oxymetholone. There were no differences between the two groups when comparing age, sex, etiology of aplasia, disease duration, severity of aplasia, or pretherapy granulocyte counts. Side effects of LDM and HDM were similar. Of the 64 patients evaluable for response to therapy, 12 of 33 (36%) who received LDM had complete, partial, or minimal responses compared with 15 of 31 patients (48%) who received HDM (P = .33). Actuarial survival at 4 years is 43% for patients in the LDM group and 47% for patients in the HDM group (P = .99). Causes of death included hemorrhage, infection, evolution to acute leukemia, and complications of subsequent bone marrow transplantation. Long-term complications included paroxysmal nocturnal hemoglobinuria (n = 3), evolution to myelodysplasia or acute leukemia (n = 6), and recurrent aplasia (n = 6). We were unable to show a significant difference in toxicity, response rate, or survival for patients treated with ATG, oxymetholone, and LDM compared with patients who received ATG, oxymetholone, and HDM. PMID- 1586709 TI - Phase II trial of recombinant human granulocyte-macrophage colony-stimulating factor in patients undergoing allogeneic bone marrow transplantation from unrelated donors. AB - The safety and possible efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) were evaluated in 40 consecutive patients who received transplants from unrelated donors. rhGM-CSF was administered by 2 hour daily intravenous infusion from day 0 to day 20 or day 27 after the marrow infusion. These patients were compared with 78 historical patients who received transplants from unrelated donors who did not receive rhGM-CSF. The rhGM-CSF treated patients were older (P = .037) and were treated less frequently in laminar air flow rooms (P = .005) than were control patients. However, the rhGM CSF-treated group had a higher proportion of "good risk" patients with chronic myelogenous leukemia in chronic phase (P = .006) than did the comparison group (P = .017), rendering comparisons of transplant-related complications not meaningful. rhGM-CSF was well tolerated and did not adversely increase the incidence of graft rejection or increase the incidence and severity of acute graft-versus-host disease. The median day the absolute neutrophil count reached 500/mm3 in patients who received rhGM-CSF was day 21, which was not different from that of historical patients. Nevertheless, the numbers of febrile days and septicemic episodes within the first 28 days in patients who received rhGM-CSF were less than in historical patients. The probability of nonrelapse mortality at 1 year in patients who received rhGM-CSF was 22%. In view of the retrospective nature of the control group, we cannot conclusively determine whether rhGM-CSF administration was beneficial. A prospective, randomized controlled study of rhGM CSF is required to confirm these suggestive data. PMID- 1586710 TI - Allogeneic bone marrow transplantation for acute myeloid leukemia in first remission: a randomized trial of a busulfan-Cytoxan versus Cytoxan-total body irradiation as preparative regimen: a report from the Group d'Etudes de la Greffe de Moelle Osseuse. AB - From October 1987 to December 1990, 101 patients with acute myeloid leukemia (AML) were randomized to be transplanted in first complete remission (CR1). Preparative regimen including Cytoxan (120 mg/kg) with total body irradiation (CYTBI) (N = 50) or busulfan (16 mg/kg) (BUSCY) (N = 51) was followed by allogeneic bone marrow transplantation (BMT) from an HLA-identical sibling. Mean time between diagnosis and BMT was 119 days. The outcome for CYTBI at 2 years is better for probability of disease-free survival (DFS) (72% v 47%) (P less than .01), survival (75% v 51%) (P less than .02), relapse (14% v 34%) (P less than .04), and transplant mortality (8% v 27%) (P less than .06). In multivariable analysis, higher relapse and decreased survival and DFS were associated with BUSCY regimen, while chronic graft-versus-host disease also influenced independently the probability of relapse. This demonstrates the present limitation of busulfan use in this setting, possibly due to probable individual variations in biodisponibility. Furthermore, besides the anti-leukemic effect of preparative regimens, this trial points out the progress accomplished in BMT management (transplant mortality = 8% in CYTBI) over the last 20 years as well as the effectiveness of transplant in early first CR after CYTBI (DFS = 72% at 2 years). PMID- 1586711 TI - Sequential in vivo treatment with two recombinant human hematopoietic growth factors (interleukin-3 and granulocyte-macrophage colony-stimulating factor) as a new therapeutic modality to stimulate hematopoiesis: results of a phase I study. AB - In a phase I study, the sequentially administered combination of recombinant human interleukin-3 (rhIL-3) and rhGM-CSF was compared with treatment with rhIL-3 alone in 15 patients with advanced tumors but normal hematopoiesis. Patients were initially treated with rhIL-3 for 15 days. After a treatment-free interval, the patients received a second 5-day cycle of rhIL-3 at an identical dosage, immediately followed by a 10-day course of rhGM-CSF, to assess the toxicity and biologic effects of this sequential rhIL-3/rhGM-CSF combination. rhIL-3 doses tested were 125, and 250 micrograms/m2, whereas rhGM-CSF was administered at a daily dosage of 250 micrograms/m2. Both cytokines were administered by subcutaneous (SC) bolus injection. rhIL-3/rhGM-CSF treatment was more effective than rhIL-3 but equally effective to each other in increasing peripheral leukocyte counts, especially neutrophilic and eosinophilic granulocyte counts. In contrast, both modes of cytokine therapy raised the platelet counts to the same degree. rhIL-3/GM-CSF treatment was more effective than rhIL-3 in increasing the number of circulating hematopoietic progenitor cells BFU-E and CFU-GM. High-dose rhIL-3, but not low-dose rhIL-3, was as effective as the rhIL-3/rhGM-CSF combinations in increasing the number of circulating CFU-GEMM. The increase in absolute neutrophil counts correlated with the increase in the number of circulating CFU-GM. Side effects, mainly fever, headache, flushing, and sweating, were generally mild, but in two patients the occurrence of chills, rigor, and dyspnea after initiation of GM-CSF treatment necessitated dose reduction and discontinuation, respectively. These results indicate that sequential treatment with rhIL-3 and rhGM-CSF is as effective as single-factor treatment with rhIL-3 in stimulating platelet counts, whereas the effect of combination therapy on neutrophil counts and circulating progenitor cells is superior. PMID- 1586712 TI - Macrophage-inflammatory protein protects multipotent hematopoietic cells from the cytotoxic effects of hydroxyurea in vivo. AB - Macrophage inflammatory protein-1 alpha (MIP-1 alpha) has been assessed for its potential in vivo to protect hematopoietic progenitor cells from the cytotoxic effects of a cycle-specific drug--in this case hydroxyurea (HU). Two doses of HU, 7 hours apart, were administered to mice to induce spleen colony-forming unit (CFU-S) cycling and then to kill them during DNA-synthesis. MIP-1 alpha, in a variety of dose and time combinations, was injected before the second dose of HU in an attempt to prevent recruitment or maintain CFU-S quiescence, and thus protect them from the second dose of HU. Without MIP-1 alpha, recovery of the CFU S population was complete in 7 days. In a dose-dependent manner, MIP-1 alpha either reduced the initial kill and accelerated recovery, or completely protected the CFU-S population. We conclude that MIP-1 alpha does protect multipotent progenitor cells in vivo and that these observations provide a base from which to build practical clinical applications. PMID- 1586713 TI - Recombinant human interleukin-3 and recombinant human granulocyte-macrophage colony-stimulating factor administered in vivo after high-dose cyclophosphamide cancer chemotherapy: effect on hematopoiesis and microenvironment in human bone marrow. AB - The effects on bone marrow (BM) cell proliferation and differentiation of recombinant human interleukin-3 (rhIL-3) and recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) administered after high-dose (7 g/m2/d) cyclophosphamide (HD-CTX) chemotherapy were studied in nine patients with malignancies without BM involvement and in three control patients. rhIL-3 at a dose of 1 to 5 micrograms/kg/day was administered for 14 to 18 days by continuous intravenous (i.v.) infusion and rhGM-CSF was administered at a dose of 5.5 micrograms/kg/day for 14 days. Changes induced by cytokine treatment were assessed by morphoimmunohistochemical analysis of BM biopsies. Comparison was made in the cytokine-treated groups and with control patients who received HD-CTX alone. BM cellularity and the myeloid/erythroid (ME) ratio were lower in rhIL-3 treated than in rhGM-CSF-treated patients, but in both groups it was significantly higher than in the controls. The proportion of BM cells stained by PC10, a monoclonal antibody (MoAb) recognizing a proliferation-associated nuclear protein (PCNA), increased from 6.78% to 21.18% (P less than .02) after rhIL-3, and from 5% to 35.33% (P less than .001) after rhGM-CSF; no increase was observed in the control group. The frequency of CD34+ BM cells was unchanged after rhIL-3 (P = NS) and decreased after rhGM-CSF (P less than .001). In both groups, most of the PC10+ cells were represented by promyelocytes and myelocytes with no increase in blast cell numbers. rhIL-3-treated BM showed an increased number of megakaryocytes and increased proliferative activity of erythroid cells as compared with rhGM-CSF cases. BM stroma changes observed in both treated groups included endothelial cell proliferation, increased BM macrophage concentration, and increase in BM fibroblasts as detected with an anti-nerve growth factor receptor antibody. In most rhIL-3-treated cases, BM fibrosis developed after treatment. The same effect was not observed in rhGM-CSF patients. PMID- 1586714 TI - Characterization of the gamma chain platelet binding site on fibrinogen fragment D. AB - Glycoprotein (GP) IIb/IIIa on adenosine diphosphate (ADP)-activated human platelets interacts with specific sites on the fibrinogen molecule leading to aggregation. We characterized the platelet-binding site on the gamma chains of fibrinogen using plasmic fragments D gamma A and D gamma'. Fragment D gamma A, which contains the carboxy terminal gamma A400-411 platelet-binding sequence (HHLGGAKQAGDV), was 70-fold more active than the synthetic gamma A400-411 peptide in inhibiting ADP-induced platelet aggregation. Fragment D gamma A inhibited fibrinogen binding and also bound directly to ADP-activated platelets. The Kd values determined for fibrinogen and fragment D gamma A binding were 0.55 mumol/L and 1.2 mumol/L, respectively. In contrast, fragment D gamma', which differs from fragment D gamma A with respect to its gamma chain sequence from position 408 to the COOH-terminus at position 427, did not inhibit platelet aggregation or fibrinogen binding, and did not bind directly to the platelet surface. Denaturation of fragment D gamma A with guanidine-HCl caused a loss of inhibitory activity in platelet aggregation assays. These data indicate that the native conformation of the gamma chain platelet-binding site on fibrinogen is important for optimal binding to GPIIb/IIIa. PMID- 1586715 TI - Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils. AB - Nerve growth factor (NGF) is a neurotrophic cytokine known to regulate the survival and function of peripheral and central neuronal cells. Recently, the spectrum of action could be extended to non-neuronal cell types such as rat mast cells and human B lymphocytes. The present study shows that NGF affects the function of mature human basophils isolated from the peripheral blood of healthy donors. Both murine NGF 7S and recombinant human NGF beta enhance histamine release and strongly modulate the formation of lipid mediators by basophils in response to various stimuli. This priming effect of NGF on basophils occurs rapidly within 10 to 15 minutes of preincubation, is dose-dependent, and requires similarly low concentrations (1 to 40 pmol/L) of human NGF beta as the induction of neurite outgrowth in ganglion cells. Cell fractionation studies indicate that NGF acts directly on human basophils without an involvement of other cell types, suggesting the presence of high-affinity NGF receptors on basophils. NGF by itself (up to 4 nmol/L of human NGF beta) does not induce the release of inflammatory mediators directly. The effect of human NGF on basophil mediator release is similar to that of the hematopoietic growth factors interleukin-3, interleukin-5, and granulocyte-macrophage colony-stimulating factor. The present study further demonstrates that NGF acts as a pleiotropic cytokine at the interface between the nervous and the immune system, and that NGF may be involved in inflammatory processes and hypersensitivity reactions. PMID- 1586716 TI - Productive human immunodeficiency virus-1 infection of megakaryocytic cells is enhanced by tumor necrosis factor-alpha. AB - Recent findings have indicated that megakaryocytes may be susceptible to human immunodeficiency virus (HIV) infection, suggesting a potential role for megakaryocytes as viral reservoirs in HIV-infected patients. We report that the megakaryocytic cell line Dami could be productively infected with the HTLV III-B strain of HIV-1, in 26 different experiments (results of 16 experiments are reported); productive infection lasted up to 30 weeks. Despite a lack of detectable surface expression of the CD4 molecule and very low levels of CD4 mRNA, between 40% and 60% of megakaryocytic cells produced viral proteins after contact with HIV-1. Neither cytopathogenic effects nor syncytial formation was observed. Production of high levels of functional viral particles was indicated by analysis of p24 protein levels, reverse transcriptase activity, ultrastructural studies, and the capacity of supernatants from infected Dami cells to infect the Molt-4 T-lymphocytic cell line. HIV-1 RNA and protein levels in infected Dami cells were enhanced by treatment with tumor necrosis factor alpha (TNF-alpha), and decreased by treatment with interferon-alpha (IFN-alpha) and IFN-gamma. Transient transfection of the megakaryocytic cells with various constructs of the HIV-1 promoter (LTR) linked to the luciferase reporter gene suggested that the effect of TNF-alpha was related, as in monocytic and T-cell lines, to transactivation of the enhancer region of the HIV-1 LTR. These findings indicate that signals provided by the immune system may modulate HIV-1 expression in cells of the megakaryocytic lineage. PMID- 1586717 TI - Differential expression of very late activation antigen-3 (VLA-3)/VLA-4 in B-cell non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. AB - The expression of beta 1 (very late activation antigens, VLA 1-6) and beta 2 integrins (leukocyte adhesion molecules [Leu-CAM]) in cell suspensions from the peripheral blood of 70 patients with B-cell chronic lymphocytic leukemia (B-CLL), 15 patients with leukemic lymphocytic lymphoma of intermediate differentiation (IDL), as well as from the lymph nodes of 20 patients with low/intermediate-grade non-Hodgkin's lymphoma (NHL) was studied with the aim of characterizing their adhesive phenotype and evaluating its relationship to clinical behavior. CD11a(LFA-1) was more expressed in NHL and IDL than in B-CLL (P = .047), although it was demonstrable in 74.2% of cases; CD11c was more expressed in B-CLL (P less than .0001), and its expression was preserved in almost all of the cases of small lymphocytic lymphoma. In NHL patients, including the cases of IDL, VLA-3 expression was observable in 8 of 35 cases (although always at a low level of intensity), while VLA-4 was almost constantly expressed in a way that was similar to its expression in control normal B cells. On the contrary, in B-CLL patients, VLA-3 was expressed (prevalently at high levels) in 87.1% of cases and VLA-4 only in 37.1%. No correlation was found between adhesion molecule patterns and the clinical features of the diseases. The biofunctional significance of the imbalance of VLA-3 and VLA-4 expression in B-CLL is not easy to explain, but it has undoubted intrinsic value as an additional marker for distinguishing B-CLL from, in particular, those B-cell neoplasms (such as IDL) that share many of the immunocytomorphologic characteristics and the putative normal counterpart (the mantle zone) of B-CLL. PMID- 1586718 TI - B-myb antisense oligonucleotides inhibit proliferation of human hematopoietic cell lines. AB - The B-myb gene is highly homologous to the c-myb protooncogene in several domains and also shares some of the functions of c-myb in that it can act as a transcriptional activator. In addition, the expression of both the B-myb and c myb genes correlates with proliferation of normal hematopoietic cells. We investigated more directly the role of B-myb in proliferation of hematopoietic cell lines using B-myb-specific antisense oligonucleotides. We showed that several anti-B-myb oligonucleotides, complementary to distinct regions of the gene, inhibit significantly and in a dose-dependent manner the proliferation of all myeloid or lymphoid cell lines tested. This block in proliferation was not accompanied by detectable differentiation of U937 or HL60 cells to macrophages or granulocytes either spontaneously or after exposure to chemical agents. These data suggest that the B-myb gene, like c-myb, is necessary for hematopoietic cell proliferation. PMID- 1586719 TI - Release of platelet-activating factor is important for the respiratory burst induced in human eosinophils by opsonized particles. AB - The respiratory burst induced in human eosinophils by serum-treated zymosan (STZ) was found to be almost completely prevented by preincubation of the cells with WEB 2086, an antagonist of platelet-activating factor (PAF). When eosinophils were primed by the addition of 1 mumol/L PAF, subsequent addition of WEB 2086 had only a minor effect on the STZ-induced respiratory burst. These results suggest a role for PAF synthesis and PAF release in the activation of the respiratory burst by STZ. Indeed, supernatant of STZ-stimulated eosinophils was able to prime fresh eosinophils (as did PAF itself), and this effect was again inhibited by WEB 2086. This indicates that eosinophils synthesize and release PAF during STZ stimulation. Measurements of total PAF and PAF release showed that most of the PAF synthesized by eosinophils was released in the extracellular medium. This study shows that synthesis and release of PAF is important for respiratory burst activity induced in human eosinophils by STZ. PMID- 1586720 TI - Transcriptional and posttranscriptional modulation of human neutrophil elastase gene expression. AB - Human neutrophil elastase (NE), a 29-Kd potent serine protease stored in azurophilic granules of mature neutrophils, is coded for by the NE gene, a single copy gene with 5 exons spanning a 6-kb segment of chromosome 11 at q14. With the knowledge that the NE gene expression is limited to early myeloid cell differentiation, mechanisms modulating expression of the NE gene were evaluated in the HL-60 promyelocytic leukemia cell line, a model of early bone marrow precursor cells. Consistent with the presence of NE messenger RNA (mRNA) transcripts in undifferentiated HL-60 cells, nuclear transcription run-on analyses showed that HL-60 cells actively transcribed the NE gene. However, the transcription rate of the NE gene was relatively low, only 40% of the myeloperoxidase gene, a gene expressed in parallel with NE. When induced toward the mononuclear phagocytic lineage with phorbol 12-myristate 13-acetate (PMA), HL 60 cells exhibited marked suppression of NE gene transcription, declining to 17% of the resting rate within 2 days. Induction toward mononuclear phagocytic lineage differentiation caused no change in NE mRNA transcript half-life (T1/2), but mRNA levels decreased markedly over time, with levels undetectable 1.5 days after PMA stimulation. In contrast, when induced toward the myelocytic lineage with dimethyl sulfoxide, the rate of NE gene transcription increased 1.9-fold within 5 days. Interestingly, the mRNA transcript levels increased 2.5-fold by 5 days despite the fact that induction toward myelocytic lineage differentiation was accompanied by a marked reduction of NE mRNA transcript T1/2. Together, these observations suggest that the NE gene expression during bone marrow differentiation is modulated mainly at the transcriptional level, with some posttranscriptional modulation contributing, particularly during myelocytic lineage differentiation. PMID- 1586721 TI - Reduction of tissue iron stores and normalization of serum ferritin during treatment with the oral iron chelator L1 in thalassemia intermedia. AB - In patients with thalassemia intermedia in whom hyperabsorption of iron may result in serious organ dysfunction, an orally effective iron-chelating drug would have major therapeutic advantages, especially for the many patients with thalassemia intermedia in the Third World. We report reduction in tissue iron stores and normalization of serum ferritin concentration after 9-month therapy with the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one (L1) in a 29-year-old man with thalassemia intermedia and clinically significant iron overload (SF 2,174 micrograms/L, transferrin saturation 100%; elevated AST and ALT, abnormal cardiac radionuclide angiogram) who was enrolled in the study with L1 75 mg/kg/day after he refused deferoxamine therapy. L1-Induced 24-hour urinary iron excretion during the first 6 months of therapy was (mean +/- SD, range) 53 +/- 30 (11 to 109) mg (0.77 mg/kg), declining during the last 3 months of L1 to 24 +/- 14 (13-40) mg (0.36 mg/kg), as serum ferritin decreased steadily to normal range (present value, 251 micrograms/L). Dramatic improvement in signal intensity of the liver and mild improvement in that of the heart was shown by comparison of T1 weighted spin echo magnetic resonance imaging with images obtained immediately before L1 administration was observed after 9 months of L1 therapy. Hepatic iron concentration decreased from 14.6 mg/g dry weight of liver before L1 therapy to 1.9 mg/g liver after 9 months of therapy. This constitutes the first report of normalization of serum ferritin concentration in parallel with demonstrated reduction in tissue iron stores as a result of treatment with L1. Use of L1 as a therapeutic option in patients with thalassemia intermedia and iron overload appears warranted. PMID- 1586722 TI - Molecular abnormalities of a phosphoglycerate kinase variant generated by spontaneous mutation. AB - A new case of X chromosome-linked phosphoglycerate kinase (PGK) abnormality is described. The male proband was mentally retarded, had behavior disorders, and displayed episodes of hemolytic anemia. The enzyme activity of red blood cells from the patient was about 10% of normal, and that of the cultured fibroblasts was about 50% of normal cells. The variant PGK was characterized by a lower affinity for the substrates, reduced thermostability, and increased anodal electrophoretic mobility. The pH activity profile of the variant enzyme was different from that of normal. The amount of messenger RNA (mRNA) in the variant fibroblasts was comparable to that of normal fibroblasts. The mRNA coding for PGK was subjected to coupled reverse transcription followed by amplification by the polymerase chain reaction. Nucleotide sequence of the variant cDNA showed a point mutation, T/A----C/G transition, in exon 9 of the variant gene. No other mutation was found in all coding regions of the variant. The mutation should cause Cys--- Arg substitution at the 315th position from the NH2-terminal Ser of PGK, and it created an additional Ava II (or isoschimatic) cleavage site in the variant gene. Because the variant gene was not detected in the proband's mother and siblings, it must have been generated by spontaneous mutation during oogenesis. PMID- 1586723 TI - Should HLA-identical sibling bone marrow transplants for leukemia be restricted to large centers? AB - There is substantial evidence that the volume of medical procedures in a hospital has an inverse relationship with mortality. We analyzed data for 1313 recipients of HLA-identical sibling bone marrow transplants for early leukemia (acute leukemia in first remission or chronic myelogenous leukemia in first chronic phase) to determine whether transplant outcome differed in small and large centers. Transplants were performed in 86 bone marrow transplant centers active between the years 1983 and 1988, which participated in the International Bone Marrow Transplant Registry. Twenty-one (24%) centers performed five or fewer allogeneic transplants per year during the study period; five (6%) performed more than 40 per year. After adjustment for differences in patient and disease characteristics, the relative risks of treatment-related mortality (1.53, P less than .01) and treatment failure (1.38, P less than .04) were higher among patients who received transplants at centers doing five or fewer transplants per year than among those at larger centers. Among patients receiving transplants in centers performing more than five transplants a year, there was no statistically significant correlation between number of transplants and outcome. PMID- 1586724 TI - Evolution of mixed chimerism after allogeneic bone marrow transplantation as determined on granulocytes and mononuclear cells by the polymerase chain reaction. AB - To evaluate the clinical relevance of mixed chimerism (MC) after allogeneic bone marrow transplantation (BMT), we developed a method based on amplification of DNA minisatellites by the polymerase chain reaction (PCR). This sensitive method by which MC lower than 1% can be detected is applicable to any patient-donor pair. Furthermore, because the analysis requires only small amounts of DNA, it allowed us to analyze samples early after BMT and during graft rejection. Results were obtained within 48 hours after blood sampling. Determination of MC in granulocytes (GR) and in mononuclear cells (Mnc) was performed in 20 patients treated for various hematologic malignancies. In patients who received untreated BM, recipient cells disappeared rapidly after BMT. In patients transplanted with T-cell-depleted BM, MC occurred in 15 of 16 cases. The percentage of host Mnc was always significantly higher than the percentage of host GR. The evolution of MC in patients who received T-cell-depleted marrow showed distinct patterns depending on whether patients remained in continuous complete remission, relapsed, or rejected their grafts. During complete remission, a relatively stable and significant number of host cells could be detected during the first 2 years after transplantation. Thereafter, their number decreased, but even after 4 years, low numbers of host cells could persist. When the patients relapsed, an increase in host Mnc was monitored without significant changes in the number of donor Mnc. In contrast, after the relapse, donor GR were no longer detected. Two cases of graft rejection were studied. Directly after the onset of the rejection, donor GR and Mnc disappeared rapidly. During that period, no significant changes in the number of host Mnc were detected. PMID- 1586725 TI - Marked increase in veno-occlusive disease of the liver associated with methotrexate use for graft-versus-host disease prophylaxis in patients receiving busulfan/cyclophosphamide. AB - The use of cyclosporine-A/methotrexate (CyA/MTX) for graft-versus-host disease (GVHD) prophylaxis is safe and effective for patients undergoing allogeneic bone marrow transplantation after preparation with cyclophosphamide and total body irradiation. We report 87 patients prepared for allogeneic transplant with busulfan 4 mg/kg/d orally for 4 days, followed by cyclophosphamide 60 mg/kg/d intravenously for 2 days (Bu4Cy2). A marked increase in hepatotoxicity was observed in 20 patients administered CyA/MTX, compared with 67 historical control patients who received CyA/methylprednisolone (CyA/MP) for GVHD prophylaxis with all other treatment and support variables remaining constant. The incidence of hyperbilirubinemia (bilirubin greater than or equal to 2 mg/dL) increased from 48% to 80% (P = .02), and the mean maximal bilirubin increased from 4.67 +/- 7.27 to 8.72 +/- 8.73 mg/dL (P = .04), when CyA/MTX was used in place of CyA/MP for GVHD prophylaxis. In addition, the incidence of veno-occlusive disease (VOD) increased from 18% to 70% (P = .0001), and death caused by VOD increased from 4.5% to 25% (P = .02). Survival was not significantly different for the two groups because of a higher non-VOD death rate in patients receiving CyA/MP for GVHD prophylaxis (P = .77). We suggest caution when using Bu4Cy2 in combination with CyA/MTX for GVHD prophylaxis. PMID- 1586726 TI - Altered iron metabolism and the anemia of chronic disease: a role of immune activation. PMID- 1586727 TI - Granulocyte-macrophage colony-stimulating factor-related eosinophilia and Loeffler's endocarditis. PMID- 1586728 TI - Clinical relevance of acute mixed-lineage leukemia. PMID- 1586729 TI - Purity of factor VIII concentrates and immune function in hemophiliacs. PMID- 1586730 TI - A beta-thalassemia variant associated with unusually high hemoglobin A2 in an Iranian family. PMID- 1586731 TI - Recurrence of Philadelphia chromosome-positive leukemia in donor cells after marrow transplantation for chronic granulocytic leukemia: confirmation by microsatellite studies. PMID- 1586732 TI - The biological chemistry of folate receptors. PMID- 1586733 TI - Prevention of hepatic veno-occlusive disease after bone marrow transplantation by continuous infusion of low-dose heparin: a prospective, randomized trial. AB - Hepatic veno-occlusive disease (VOD) is a major regimen-related toxicity after bone marrow transplantation (BMT). Endothelial injury, leading to deposition of coagulation factors within the terminal hepatic venules, is believed to be the key event in the pathogenesis of VOD. To evaluate the benefit and the safety of a VOD prophylaxis with anticoagulants, we conducted a prospective randomized trial of continuous infusion of low-dose heparin among 161 patients under-going either allogeneic (n = 79) or autologous BMT (n = 81). Patients were randomized to receive (n = 81) or not receive (n = 80) prophylactic heparin 100 U/kg/d by continuous infusion from day -8 until day +30 post-BMT. Heparin was found to be highly effective in preventing VOD, which occurred in 11 of 80 patients (13.7%) in the control group versus 2 of 81 (2.5%) in the heparin group (P less than .01). Furthermore, none of the 39 patients in the heparin group developed VOD after allogeneic BMT, versus 7 of 38 (18.4%) in the control group (P less than .01). This prophylactic effect was achieved without added risk of bleeding. Indeed, the low-dose heparin we used did not prolong the partial thromboplastin time and did not increase the red blood cell and platelet requirements. It is therefore recommended that heparin prophylaxis be part of early mortality prevention programs after BMT. PMID- 1586734 TI - Introduction of the human interleukin-6 (IL-6) receptor in murine IL-3-dependent hematopoietic cells restores responsiveness to IL-6. AB - To create experimental systems that facilitate studies aimed at the responsiveness of hematopoietic progenitors to interleukin (IL)-6 in combination with IL-3, we introduced the human IL-6 receptor (hIL-6R) into the IL-3-dependent cell line 32D. For this purpose, a retroviral vector containing the hIL-6R cDNA was constructed. 32D parental cells did not respond to IL-6, neither alone nor in combination with increasing concentrations of IL-3, and did not express detectable numbers of IL-6R as determined by 125I-IL-6 binding. 32D/hIL-6R cells expressed high-affinity IL-6 binding and responded synergistically to IL-6 in combination with suboptimal amounts of IL-3 in DNA synthesis assays. In addition, IL-6 promoted the short-term survival of IL-3-responsive clonogenic 32D/hIL-6R cells. On the other hand, although introduction of hIL-6R resulted in the formation of high-affinity IL-6 receptor structures in the IL-2-dependent thymocyte cell line CTLL, CTLL/hIL-6R cells did not respond to IL-6 in synergy with IL-2. We conclude that 32D cells possess the intracellular machinery permissive for IL-6 signal transduction. Murine IL-3-dependent cell lines with ectopic IL-6 receptors can serve as models for dissecting the molecular basis of IL-6 responses in primitive hematopoietic cells. PMID- 1586735 TI - Acetylcholinesterase in murine erythroleukemia (Friend) cells: evidence for megakaryocyte-like expression and potential growth-regulatory role of enzyme activity. AB - Features of true acetylcholinesterase (AChE) regulation during growth and differentiation of Friend murine erythroleukemia cells (MELC) have been investigated with respect to other erythroid and nonerythroid murine elements. Enzyme levels of uninduced MELC were in between the very low AChE contents of erythroid cells and the huge amounts of activity exhibited by megakaryocytes and platelets. After MELC commitment to terminal division, the enzyme-specific activity increased largely, approaching values that were much closer to those of thrombocytic than of normal erythroid elements. The bulk of AChE activity in MELC, megakaryocytes, and platelets was found to be located in the cytosol as a free-soluble form. Moreover, during incubation, MELC actively released large amounts of AChE into the medium, like it occurs in murine thrombocytes. Conversely, the enzyme of the erythroid elements was mainly associated with the membranes and was not released extracellularly. Experiments with inducers showed that changes in AChE-specific activity of MELC correlated directly with the arrest of cell proliferation rather than with the activation of differentiated erythroid functions. The inverse relationship existing between MELC growth rates and AChE levels was further supported by the relative enzyme activities of the slow- and fast-growing subclones. We conclude that uninduced MELC potentially share properties of both the erythroid and megakaryoblastic phenotype. The latter might be revealed by typical regulation of AChE activity according to a thrombocytic-like program activated upon MELC commitment to terminal division. Eventually, the inhibition of MELC growth by exogenous pure bovine AChE suggested that the secreted murine enzyme might serve as a potential negative signal of cellular replication. PMID- 1586736 TI - Induction of tissue factor activity in endothelial cells and monocytes by a modified form of albumin present in normal human plasma. AB - Molecules that induce tissue factor expression by responsive cells such as endothelial cells and monocytes may be important in the regulation of hemostasis and, perhaps, in mediating certain hemostatic disorders. A constituent of normal human plasma capable of inducing tissue factor activity in human endothelial cells and monocytes has been isolated and identified as a derivative of, or modification associated with albumin. Procoagulant albumin caused a concentration dependent induction of tissue factor expression by human endothelial cells, but bovine endothelial cells were unresponsive. The dose-response curve developed a plateau phase, indicating that the capacity of endothelial cells to respond to the stimulus was finite. The maximum response induced by the procoagulant albumin was similar to that observed for maximally effective concentrations of endotoxin, interleukin-1, and tumor necrosis factor. Time-course studies showed that procoagulant albumin produced peak activity in 4 to 6 hours. Identification of a procoagulant form of albumin in normal human plasma suggests a potential role for this constituent in regulation of hemostasis. PMID- 1586737 TI - Platelet activation by cross-linking HLA class I molecules and Fc receptor. AB - The effect on platelet activation of monoclonal antibodies directed against common determinants of the HLA class I heavy chain molecule was studied. Cross linking W6/32, an anti-HLA class I of IgG2a subclass, led to platelet activation. Two other antibodies of the same subclass did not have this effect on platelets. The lack of activity of the F(ab')2 fragments suggests that the activation signal is mediated by the platelet Fc receptor (Fc gamma RII). Indeed, except for a higher sensitivity of W6/32 to aspirin and apyrase, activations by cross-linking IV-3 (an anti-Fc gamma RII) and W6/32 are similar at the level of InsP3 formation, calcium mobilization, pH modifications, and activation of protein kinase C and myosin kinase. When HLA class I molecules and Fc gamma RII are cross linked together, platelet activation occurs. This is not observed when a control IgG2a is substituted for W6/32 or when CD9 and Fc receptor are cross-linked together. This suggests that HLA class I molecules and Fc gamma RII synergize to activate platelets. PMID- 1586738 TI - Activation of factor X and its regulation by tissue factor pathway inhibitor in small-diameter capillaries lined with human endothelial cells. AB - The activation of factor X at the surface of endothelial cells was investigated under controlled flow conditions. A method is described for preparing polyethylene capillaries whose inner walls are covered with a confluent layer of human umbilical vein endothelial cells. To obtain a stable and unperturbed layer of endothelial cells it was essential to pre-perfuse the endothelialized capillaries with medium for about 18 hours. At this stage no tissue factor activity could be detected, but when the seeded cells were perfused with medium containing tumor necrosis factor (TNF) a maximum steady-state rate of factor Xa production (16 fmol factor Xa/min/cm2) was observed within 8 hours. Further experiments were performed with endothelial cells incubated for 4 hours with TNF. Factor Xa was produced at a rate of 7 fmol factor Xa/min/cm2 on perfusion of the capillaries with factor X (100 nmol/L) and factor VII (0.1 U/mL) at a shear rate of 34 s-1. The extracellular matrix preparations of these cells produced factor Xa at a 20-fold higher rate (150 fmol factor Xa/min/cm2). In both cases factor Xa formation was dependent on the presence of factor VII and was completely inhibited when the perfusate also contained 5 nmol/L recombinant tissue factor pathway inhibitor (rTFPI). Pre-perfusion with factor Xa-TFPI complex in the absence of factor VIIa caused a much lesser inhibitory effect, suggesting that TFPI-mediated neutralization of endothelial cell and matrix tissue factor activity requires the presence of factor VIIa in addition to the presence of factor Xa. PMID- 1586739 TI - Migration of primed human eosinophils across cytokine-activated endothelial cell monolayers. AB - Eosinophils are known to adhere to cytokine-activated endothelium. Whereas transendothelial migration for neutrophils is an inevitable consequence of this endothelial-dependent adherence, this has not yet been shown for eosinophils. By means of human umbilical vein endothelial cells (HUVE) grown to confluence on microporous filters as an in vitro model of leukocytic migration across postcapillary venules, we have characterized the conditions leading to endothelium-driven transmigration of blood eosinophils from normals and from patients with allergic asthma. Freshly isolated eosinophils from nonallergic donors adhered to interleukin-1 (IL-1) and tumor necrosis factor-activated HUVE, but did not penetrate these monolayers. In contrast, eosinophils from allergic asthma patients showed an increased adherence and transmigration capacity. This increased functional competence was not caused by a difference in density phenotype, because the eosinophils from both groups showed a comparable density distribution over discontinuous Percoll gradients. Moreover, no difference existed within one group among eosinophils harvested from the Percoll density bands 1.080, 1.085, and 1.090 g/mL in terms of transendothelial migration. In vitro cultivation of freshly isolated eosinophils from nonallergic individuals in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL 3 induced a stepwise decrease of the density distribution over such gradients. In contrast, eosinophils from patients with allergic asthma directly shifted to a final density of 1.075 g/mL within 24 hours of culture. Notwithstanding the kinetics of density changes, eosinophils from nonallergic donors already expressed the capacity to transmigrate IL-1-activated HUVE monolayers 20 hours after cultivation with different combinations of GM-CSF, IL-3, and IL-5. Inhibition studies with monoclonal antibodies showed that endothelium-driven transmigration of eosinophils predominantly implicates CD11/CD18 structures on the eosinophil surface, whereas no significant inhibition was found with the anti VLA-4 monoclonal antibody HP2/1. From cytofluorometric studies, we conclude that spontaneous transmigration of eosinophils from allergic asthma patients is not accompanied by quantitative upregulation of these antigens. Taken together, these results allow the conclusion that blood eosinophils from allergic asthma patients have undergone in vivo priming, mimicked in vitro by cytokines such as GM-CSF, IL 3, and IL-5, leading to induction of the capacity to migrate across cytokine activated HUVE monolayers. PMID- 1586740 TI - Origin of anti-idiotypic activity against anti-factor VIII autoantibodies in pools of normal human immunoglobulin G (IVIg). AB - Therapeutic preparations of polyspecific IgG obtained from plasma pools of a large number of normal donors (IVIg) express anti-idiotypic activity against a wide spectrum of natural and disease-associated autoantibodies. The present study investigated the origin of anti-idiotypic activity against autoantibodies to factor VIII. The neutralizing activity of pools of IgG against patients' anti factor VIII autoantibodies was not influenced by the presence of individuals with natural anti-factor VIII antibodies among donors contributing to the pool. A higher frequency of neutralizing antibodies against anti-factor VIII autoantibodies was found in aged donors as compared with young adults and in pools of IgG from multiparous women as compared with IgG from random donors. Pooling IgG from several donors synergistically enhanced the inhibitory activity of the pools. Thus, a neutralizing activity against anti-factor VIII autoantibodies was detected in pools of IgG of as few as two to four donors of whom individually tested IgG did not exhibit inhibitory activity against anti factor VIII autoantibodies. These observations suggest that aged donors and multiparous women may be privileged sources for the anti-idiotypic activity of IVIg against autoantibodies and emphasize that the expression of anti-idiotypic activity in IVIg results from a synergistic participation of anti-idiotypes from each donor contributing to the pool. PMID- 1586741 TI - Murine autoimmune hemolytic anemia resulting from Fc gamma receptor-mediated erythrophagocytosis: protection by erythropoietin but not by interleukin-3, and aggravation by granulocyte-macrophage colony-stimulating factor. AB - We have evaluated the therapeutic activity of recombinant erythropoietin (rEpo), in comparison with recombinant interleukin-3 (rIL-3) and granulocyte-macrophage colony-stimulating factor (rGM-CSF), on a lethal form of acute anemia resulting from Fc gamma receptor-mediated erythrophagocytosis after a single injection (500 micrograms) of a monoclonal anti-mouse red blood cell (MRBC) autoantibody. Continuous perfusion of rEpo before the administration of anti-MRBC monoclonal antibody completely protected animals from death due to anemia with a rapid recovery, while no protection was obtained by rIL-3 perfusion. In contrast, rGM CSF perfusion markedly accelerated the progression of anemia and the mortality rate. This was found to result from an enhancement of erythrophagocytosis by Kupffer cells and by polymorphonuclear leukocytes that massively infiltrated the livers. Even after the injection of a sublethal dose (100 micrograms) of anti MRBC monoclonal antibody, rGM-CSF-perfused mice died of a severe form of acute anemia. Furthermore, we have shown that rEpo was able to treat efficiently a spontaneous form of autoimmune hemolytic anemia in a majority of anemic NZB mice, whereas rGM-CSF markedly aggravated anemia. This may be of clinical importance, because GM-CSF administration could exhibit an adverse effect in some autoimmune diseases that involve autoimmune anemia. PMID- 1586742 TI - Evidence for in vivo clonal proliferation of unique population of blood CD4-/CD8- T cells bearing T-cell receptor alpha and beta chains in two normal men. AB - Rare T lymphocytes bearing CD3 surface antigen and T-cell receptor (TCR) alpha and beta chains, but lacking both CD4 and CD8 antigens, viz, TCR alpha beta+CD4-8 cells, appear at a frequency of 0.1% to 2% in peripheral blood TCR alpha beta+ cells of normal donors. Here we report two unusual cases, found among 100 healthy individuals studied, who showed an abnormally elevated frequency of these T cells, ie, 5% to 10% and 14% to 19%. Southern blot analyses of the TCR alpha beta+CD4-8- clones all showed the identical rearrangement patterns for each individual, demonstrating that these are derivatives of a single T cell. The same rearrangement patterns were also observed for the freshly isolated lymphocytes of TCR alpha beta+CD4-CD8- fraction, which excludes the possible bias in the processes of in vitro cloning. These TCR alpha beta+CD4-8- T cells were found to express other mature T-cell markers such as CD2, CD3, and CD5 antigens, as well as natural killer (NK) cell markers (CD11b, CD16, CD56, and CD57 antigens) for both individuals. Further, although lectin-dependent or redirected antibody dependent cell-mediated cytotoxicities were observed for both freshly sorted lymphocytes of TCR alpha beta+CD4-8- fraction and in vitro established clones, NK like activity was not detected. PMID- 1586743 TI - The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. AB - Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level. PMID- 1586744 TI - Lactoferrin gene promoter: structural integrity and nonexpression in HL60 cells. AB - Lactoferrin is a member of the transferrin family of iron-binding proteins. It is found in several glandular epithelial tissues and human neutrophils, where it is localized to secondary granules. To examine the mechanisms controlling lactoferrin gene expression in neutrophils and defects in its expression in acute leukemia, we have cloned a lactoferrin cDNA from a chronic myelogenous leukemia library, and used it to obtain genomic clones representing the chromosomal lactoferrin gene. Using polymerase chain reaction, primer extension, and S1 analysis, we have identified the 5' end of the lactoferrin mRNA. We have defined a putative promoter region for the gene, and characterized its first two exons. In addition, we have examined the structure of these regions in DNA from HL60 cells. HL60 is a leukemic cell line that undergoes phenotypic neutrophil maturation on exposure to dimethyl sulfoxide (DMSO). However, the cells cannot be induced to express any secondary granule protein genes. We have shown that the 5' end of the lactoferrin gene, including the putative promoter region, is entirely normal in HL60. By Northern analysis, nuclear run-on studies, and primer extension assays we have shown that the gene is not transcribed in DMSO-induced HL60 cells. This supports the hypothesis that the defect in HL60 is an abnormality in the production or activity of a transacting regulator of lactoferrin gene expression. PMID- 1586745 TI - Isolation, characterization, and immunoprecipitation studies of immune complexes from membranes of beta-thalassemic erythrocytes. AB - beta-Thalassemia, a hemoglobinopathy that results in the precipitation of denatured alpha-globin chains on the membrane, is characterized by erythrocytes with significantly reduced lifespans. We have demonstrated previously that hemoglobin denaturation on the membrane can promote clustering of integral membrane proteins, and that this clustering in turn leads to autologous antibody binding, complement fixation, and rapid removal of the cell by macrophages. To evaluate whether this pathway also occurs in beta-thalassemic cells, we have isolated and characterized the immune complexes from the membranes of these cells. We observe that autologous IgG-containing complexes obtained by either immunoprecipitation or simple centrifugation of nondenaturing detergent extracts of beta-thalassemic cell membranes contain globin, band 3, IgG, and complement as major components. Absorption spectra of these complexes demonstrate that the globin is, indeed, mainly in the form of hemichromes. Immunoblotting studies further show that much of the band 3 protein in the aggregates is covalently cross-linked to a dimeric or tetrameric form, consistent with the preference of the autologous IgG for clustered band 3. Although the insoluble aggregates constitute only approximately 1.6% of the total membrane protein, they still contain 27% of the total IgG and 35% of the total complement C3 on the thalassemic cell surface. Because cell surface IgG and complement component C3 are thought to trigger removal of erythrocytes from circulation, the hemichrome induced clustering of band 3 may contribute to the beta-thalassemic cell's shortened lifespan. PMID- 1586746 TI - Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene. AB - Mutations producing beta-thalassemia reach individual gene frequencies greater than .01 in malarial-endemic regions because beta-thalassemia trait individuals have increased genetic fitness over that of normal individuals. Exon 3 of the beta-globin gene has been relatively spared as a site of common beta-thalassemia mutations. Frameshifts caused by the loss of a single nucleotide and nonsense mutations produce beta-thalassemia trait when they occur in exons 1 and 2. In contrast, they usually produce chronic hemolytic anemia when present in exon 3. Certain missense mutations in exon 3 produce unstable globins and thalassemia intermedia with hemolysis in heterozygotes. Here we report two new mutations in exon 3 of the beta-globin gene. One is a single nucleotide deletion in codon 109 in a 78-year-old Lithuanian with chronic hemolytic anemia and features of thalassemia. It leads to an abnormal globin (beta Manhattan) that is elongated to 156 amino acids. The second is a CAG-CGG missense mutation at codon 127 that causes a Gln----Pro substitution (beta Houston) and a thalassemia intermedia with hemolysis in three generations of a British-American family. Although the clinical phenotypes of these two patients differed little, differences in globin synthetic ratios were significant, presumably reflecting differences in the ability of each abnormal beta-globin to form alpha beta dimers. The paucity of high-frequency exon 3 mutations and their worldwide distribution is likely attributable to their phenotypic severity and loss of increased genetic fitness vis-a-vis malaria. PMID- 1586748 TI - Bone marrow transplantation for Philadelphia chromosome-positive acute lymphoblastic leukemia. AB - Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) has a poor prognosis when treated with conventional chemotherapy. We analyzed the outcome of 67 HLA-identical sibling bone marrow transplants (BMTs) for Ph1 positive ALL reported to the International Bone Marrow Transplant Registry (IBMTR). Twenty-one of 67 (31%) transplant recipients survived in continuous complete remission more than 2 years after transplant. Two-year actuarial probabilities (95% confidence interval) of leukemia-free survival were 38% (23% to 55%) for 33 patients transplanted in first remission, 41% (23% to 61%) for 22 patients transplanted after relapse, and 25% (9% to 53%) for 12 patients failing to achieve remission with conventional chemotherapy. These data indicate that transplants are effective treatment for Ph1-positive ALL. PMID- 1586747 TI - Induction of cutaneous graft-versus-host disease by administration of cyclosporine to patients undergoing autologous bone marrow transplantation for acute myeloid leukemia. AB - Cutaneous graft-versus-host disease (GVHD) has been reported after administration of cyclosporine (CSP) after autologous bone marrow transplantation (ABMT) with unpurged marrow in patients with lymphoma. To determine whether GVHD can be induced after ABMT with chemopurged marrow in acute myeloid leukemia (AML), we administered intravenous CSP for 28 days (beginning on the day of ABMT) to 19 patients with AML (12 in first remission [CR1], six in CR2, and one in CR3) who received busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) and ABMT with 4 hydroperoxycyclophosphamide (4HC)-treated marrow. In this dose-escalation trial, CSP daily doses were 1 mg/kg in seven patients, 2.5 mg/kg in eight patients, or 3.75 mg/kg in four patients. Skin biopsies were obtained weekly after ABMT or on appearance of rash and were graded for GVH changes. Overall, 15 of 19 patients (79%) had cutaneous histopathologic grade 2 GVHD at a median of 33 days (range, 14 to 49) after ABMT; in 10, cutaneous manifestations were present at time of positive biopsy. The frequency, time to onset, and duration of GVHD were similar among the three CSP dosage groups. No patients had hepatic or gastrointestinal dysfunction attributable to GVHD or required specific therapy for GVHD. Positive biopsies for GVHD were seen in seven of eight patients who received full-course, full-dose CSP and 8 of 11 patients who had CSP discontinued or dosage reduced because of renal insufficiency. Three patients (one with positive biopsy) died with ABMT-related complications. Seven patients (four CR1, three CR2) relapsed with AML at a median of 411 days (range, 178 to 549) after ABMT; six of seven had positive biopsies for cutaneous GVHD. Nine patients (seven CR1, one CR2, and one CR3) are alive without relapse at a median of 501+ days (range, 252+ to 811+) after ABMT; eight of nine had cutaneous GVHD. Short-course CSP can induce autologous GVHD in recipients of chemopurged marrow autografts for AML, but randomized prospective trials are needed to determine whether this immunologic reaction is associated with alterations in leukemic relapse rate and disease-free survival after ABMT in AML. PMID- 1586749 TI - Hemolysis of transfused group O red blood cells in minor ABO-incompatible unrelated-donor bone marrow transplants in patients receiving cyclosporine without posttransplant methotrexate. AB - Hemolysis most commonly occurs following bone marrow transplant when there is "minor" ABO blood group incompatibility between donor and recipient. The hemolysis has been attributed to destruction of the patient's incompatible erythrocytes by donor-derived anti-A and/or anti-B antibody produced from "passenger" immunocompetent donor lymphocytes. Extraordinary transfusion requirements of group O erythrocytes in a series of patients receiving unrelated minor ABO-incompatible marrow grafts led us to investigate whether this mechanism could account for the extent of hemolysis observed. In seven consecutive minor ABO-incompatible unrelated-donor bone marrow transplant recipients receiving cyclosporine without posttransplant methotrexate, we observed excessive hemolysis. For cases in this index group, a strongly reactive donor-derived ABO blood group antibody was identified coincident with development of hemolysis. Transfusion requirements in the first three patients (26 U of group O erythrocytes each) greatly exceeded the recipient's volume of incompatible erythrocytes, indicating that lysis of transfused group O erythrocytes was also occurring. Pretransplant erythrocyte exchange transfusion with group O erythrocytes performed in the four subsequent patients decreased the severity of hemolysis, but did not prevent it. Among minor ABO-incompatible marrow graft recipients, an analysis of variance demonstrated effects on transfusion requirements due to donor-recipient relationship being unrelated (P less than .002) and the use of posttransplant methotrexate (P = .0001), and there was interaction between these two factors (P less than .001). Bone marrow transplants from unrelated donors resulted in an exaggerated immune response to ABO blood group antigens, which was associated with hemolysis of transfused group O erythrocytes, as well as the patient's ABO-incompatible erythrocytes. This serious complication may be prevented by posttransplant immunosuppression with methotrexate. PMID- 1586750 TI - Genetic and structural characterization of an amino acid dimorphism in glycoprotein Ib alpha involved in platelet transfusion refractoriness. AB - The platelet-specific alloantigen, Siba, located within the alpha-subunit of the glycoprotein (GP) Ib-IX membrane receptor, has been found to be involved in the pathogenesis of platelet transfusion refractoriness. We have identified the existence of a naturally occurring threonine/methionine dimorphism at position 145 of the GPIb alpha sequence, and determined that the Siba antigen corresponds to the molecule containing methionine145. The diallelic codons can be detected by restriction enzyme analysis of amplified genomic DNA fragments from the GPIb alpha gene. Evaluation of 61 healthy blood donors showed that the allele frequencies are 89% and 11% for the threonine145 and methionine145 codons, respectively. A positive correlation exists between platelet reactivity with the anti-Siba antibody and the presence of a methionine145-encoding allele. Moreover, recombinant expression of two soluble GPIb alpha fragments differing only at residue 145, provided definitive evidence that the human anti-Siba antibody reacts only with the molecule containing methionine145. These results explain the structural basis of the Siba human alloantigen system and define screening methodologies useful in transfusion medicine to match donor and recipient platelets accordingly. PMID- 1586751 TI - Long-term follow-up of three controlled trials comparing cyclosporine versus methotrexate for graft-versus-host disease prevention in patients given marrow grafts for leukemia. PMID- 1586752 TI - Presenting features and prognosis of B-cell chronic lymphocytic leukemia patients less than 50 years old. PMID- 1586753 TI - Globin genes are actively transcribed in the human megakaryoblastic leukemia cell line MEG-01. PMID- 1586754 TI - Relationship between M-BCR breakpoint position in blast crisis and length of chronic phase in chronic myeloid leukemia. PMID- 1586755 TI - Clinical methods of goniometry: a comparative study. AB - This investigation compared the reliability and interchangeable use of three currently available goniometers--a universal goniometer, a fluid goniometer, and an electrogoniometer. Three consecutive readings of the active range of movement of the right elbow joint were taken from each of 23 healthy female volunteers; three experienced observers each used each type of goniometer on two occasions. A balanced experimental design was used to eliminate order effects with respect to subject, tester, or goniometer, and a rigid protocol was employed to reduce error due to diurnal or methodological variations. The results show that there are significant differences between the goniometers used, the testers, and the replications. Significant interaction effects also exist between the goniometers and the occasion, the goniometers and the testers, and the testers and replications. The data suggest that the interchangeable use of different types of goniometer in a clinical setting is inadvisable. PMID- 1586756 TI - An examination of the factor structure of the Frenchay Activities Index. AB - The Frenchay Activities Index (FAI) was administered to an elderly non-stroke subject group with the objective of evaluating the underlying factor structure of the index. Data analysis yielded three factors which were labelled indoor domestic chores, outdoor domestic chores, and outdoor social activities. This factor structure is compared with that previously published. It is argued that lifestyle activities should be considered within a framework which distinguishes between indoor/outdoor and work/leisure activities. PMID- 1586757 TI - Medical and social factors affecting behaviour patterns in patients with acquired brain damage: a study of patients living at home three years after the incident. AB - This study aimed to describe the consequence of stroke or brain trauma 3 years after the incident for individuals living at home, and how patterns of behaviour were influenced by determinants. One hundred and eighty-eight individuals in three age groups answered a questionnaire. Answers were classified according to WHO's ICIDH, and 11 areas of behaviour were distinguished. Diagnoses and locations of lesions were noted from medical records. Impairment and disability increased with increasing age at the time of the incident. Individuals working before but not after the incident indicated decreased life satisfaction and changed intellectual function, personal care, and domestic/housework/gardening activities, and inability to organize their time. Those who had resumed work but at different tasks indicated changed emotional and sensorimotor function and content in leisure activities. The influence of the localization and lateralization of the lesion is also discussed. PMID- 1586758 TI - Survival, disability, and residence 20 months after acute stroke in a Chinese population: implications for community care. AB - A total of 304 Chinese patients with acute stroke were assessed at 3 and 20 months to determine survival, disability, and place of residence, and so to provide an estimate of the impact on community care resources. Approximately 30% of patients had died by 3 months; thereafter the mortality rate decreased, with a further 13% dying by 20 months. Age, rather than stroke subtype, determined the likelihood of death. Fifty-seven per cent of 3-month survivors were independent at 20 months, with only 18% moderately to severely disabled (Barthel Index less than 15). Thirteen per cent of patients improved and 14% deteriorated between 3 and 20 months. Older subjects had a lower Barthel Index at 20 months, and were more likely to show deterioration. Seventeen per cent of patients were living in institutions by 20 months, predisposing factors being age and mental test score. Although a low Barthel Index was a factor in univariate analysis, it did not contribute to the discriminant function model for predicting institutionalization, and nor did previous stroke, coexisting cardiovascular diseases, or diabetes mellitus influence eventual placement. Approximately 30% of patients were readmitted during the follow-up period, particularly elderly patients and those with a Barthel Index less than 15. Although only 9% of the original cohort required institutional care by 20 months, approximately half of all the government nursing home places in Hong Kong are likely to be taken up by these patients because of the large number of strokes occurring each year. PMID- 1586759 TI - Psychological impairments, disabilities, and handicaps: a pilot study of psychological assessment of functioning in chronic pain patients. AB - This study addresses the psychological assessment of functioning in chronic pain patients. First, a model of functional assessment is proposed, which is based on the biopsychosocial view of chronic disease (Engel) and on the consequences of diseases (WHO). Second, a set of psychological criteria for impairments, disabilities, and handicaps, described by WHO as the consequences of diseases, are determined. Third, the psychological criteria selected are operationalized and the utility of the psychological assessment instruments tested in a clinical rehabilitation study. The results indicate that prediction of post-treatment functioning in the rehabilitation patient, by psychological procedures, may improve if the concept of functioning is determined as three sub-areas of impairments, disabilities, and handicaps. PMID- 1586760 TI - The Extended Activities of Daily Living scale: a further validation. AB - The Extended Activities of Daily Living scale was validated as an overall assessment of functional independence in stroke patients discharged from hospital. Analysis of results from 49 patients discharged from a stroke unit and 299 from a trial of domiciliary rehabilitation supported previous work indicating that the four subsections--mobility, kitchen, domestic, and leisure--each formed a unidimensional hierarchical scale. Results also indicated that the scores from the subsections could be added to provide an overall score. The scale is suggested as appropriate for studies evaluating rehabilitation outcome after stroke, and is suitable for postal surveys. PMID- 1586761 TI - Community-based rehabilitation--outcome for the disabled in the Philippines and Zimbabwe. AB - OBJECTIVE: to evaluate the achievements of a CBR programme initiated for individuals ascertained in house-to-house surveys. DESIGN: assessment of changes in status for six types of disability after at least 6 months duration of the programme, with family participation. SETTING: home, school, or workplaces in villages in the Philippines and Zimbabwe. SUBJECTS: a sample of recipients of programme activities in each of the two countries. ASSESSMENTS: history, testing of ability in ADL and communication, and family discussion. RESULTS: general gain in ability scores in 78% and 93% of the samples in the two countries respectively, together with encouraging rates of starting school or taking up an occupation. CONCLUSIONS: the WHO CBR programme is highly effective for disabled people in the community being trained at home, for both children and adults, and yields similar results in different types of society; it can be accomplished at very low cost by recruiting volunteers, and mobilizes human resources in the community while promoting self-esteem. PMID- 1586762 TI - The transfer of scanning training effects in visual inattention after stroke: five single-case studies. AB - The transfer effects of scanning training of right-brain-damaged stroke patients with visual inattention have been studied. Five patients were treated according to a B-C-B-D design. The first B phase lasted for 2, 4, or 6 weeks, whereas the other intervention phases had a fixed duration of 2 weeks. During all phases physical therapy was given. Additionally, occupational therapy was applied during the B phases, training on a scanning apparatus during the C phase, and training on reading tasks during the D phase. At least three times in each intervention phase, performance was measured using a computerized visual scanning test, a line bisection test, and a letter cancellation test. In addition, wheelchair navigation was assessed. For four out of the five patients a significant positive effect of visual scanning training on visual scanning behaviour was found. This effect, however, appeared to be restricted to the task which was specifically trained. Over the group as a whole no evidence could be found for any transfer of visual scanning training effects to the domain of gross motor skills. PMID- 1586763 TI - Medical management of severe inflammatory disease of the rectum and distal colon: non-nutritional aspects. AB - Rectal bleeding is the cardinal symptom in patients with inflammation of the rectum, and initial management must be directed at establishing an underlying diagnosis. In many patients in the Western World this will be idiopathic inflammatory bowel disease, although in all cases other causes such as infection must be excluded. Idiopathic proctitis is usually due to either ulcerative colitis or Crohn's disease, and in both conditions corticosteroids, either systemic or topical, provide the mainstay of treatment. The 5-aminosalicylic acid drugs are helpful in both acute and maintenance treatment, again given either systemically or topically, while metronidazole is of value in patients with Crohn's disease. In those with refractory proctitis alternative agents such as azathioprine, immunomodulating drugs and barrier agents may be useful. Severe inflammation of the rectum secondary to pelvic irradiation will also usually respond to topical steroid therapy, although sucralfate enemas may be equally successful; in resistant cases other treatments may be needed. Infective proctitis, when diagnosed, may require treatment with specific antimicrobial agents. PMID- 1586764 TI - Indeterminate colitis. PMID- 1586765 TI - Solitary rectal ulcer syndrome. PMID- 1586766 TI - The surgical management of constipation. AB - The anal physiology laboratory plays a very important role in the selection of patients for surgical treatment for constipation. Any report which does not include reference to these methods of evaluation will not be helpful since there are several causes of constipation. The current recommended treatment for slow transit constipation is still total abdominal colectomy with ileorectal anastomosis. Treatment of pelvic floor outlet obstruction seems to be best accomplished using muscle/sensory retraining techniques since this is a functional disorder rather than an anatomical or physiological disorder. Combinations of colonic inertia, pelvic floor outlet obstruction and internal intussusception should be treated to correct the pelvic floor outlet obstruction initially, followed by correction of the colonic inertia. In this way failure will be avoided at the time of surgical treatment of the constipation. PMID- 1586767 TI - The role and technique of ambulatory anal manometry. AB - Static anal manometry has proved itself a reliable, reproducible and objective assessment of sphincter function in the investigation of disorders of defecation and continence. Despite this, it gives only very limited information on sphincter function due to the unphysiological nature of its measurement. Technical advances, particularly in digital data storage, have made the recording of anal pressure in a normal environment for prolonged periods of time possible. This offers an improved understanding both of anal activity and the interaction of rectal and anal function in normal and pathological states. In normal subjects anal function during a number of normal physiological events such as micturition, passage of flatus and sleep have been investigated. The sampling reflex has been further defined. Abnormalities of the sampling reflex, rectal activity and slow wave activity in the anal sphincter have been demonstrated in a number of pathological conditions of the anorectum and in the states of incontinence or constipation. Effective ambulatory anal manometry remains in its infancy. With continuing advances it offers exciting possibilities in defining normal or abnormal activity of the anorectum and in the investigation of patients with disorders of defecation and continence. PMID- 1586768 TI - Testing for and the role of anal and rectal sensation. AB - The rectum is insensitive to stimuli capable of causing pain and other sensations when applied to a somatic cutaneous surface. It is, however, sensitive to distension by an experimental balloon introduced through the anus, though it is not known whether it is the stretching or reflex contraction of the gut wall, or the distortion of the mesentery and adjacent structures which induces the sensation. No specific sensory receptors are seen on careful histological examination of the rectum in humans. However, myelinated and non-myelinated nerve fibres are seen adjacent to the rectal mucosa, but no intraepithelial fibres arise from these. The sensation of rectal distension travels with the parasympathetic system to S2, S3 and S4. The two main methods for quantifying rectal sensation are rectal balloon distension and mucosal electrosensitivity. The balloon is progressively distended until particular sensations are perceived by the patient. The volumes at which these sensations are perceived are recorded. Three sensory thresholds are usually defined: constant sensation of fullness, urge to defecate, and maximum tolerated volume. The modalities of anal sensation can be precisely defined. Touch, pain and temperature sensation exist in normal subjects. There is profuse innervation of the anal canal with a variety of specialized sensory nerve endings: Meissner's corpuscles which record touch sensation, Krause end-bulbs which respond to thermal stimuli, Golgi-Mazzoni bodies and pacinian corpuscles which respond to changes in tension and pressure, and genital corpuscles which respond to friction. In addition, there are large diameter free nerve endings within the epithelium. The nerve pathway for anal canal sensation is via the inferior haemorrhoidal branches of the pudendal nerve to the sacral roots of S2, S3 and S4. Anal sensation may be quantitatively measured in response to electrical stimulation. The technique involves the use of a specialized constant current generator and bipolar electrode probe inserted in the anal canal. The equipment is generally available and the technique has been shown to be an accurate and repeatable quantitative test of anal sensation. PMID- 1586769 TI - The internal anal sphincter: mechanisms of control and its role in maintaining anal continence. AB - The human IAS has particular structural and functional characteristics. This smooth muscle constantly generates rhythmic electrical slow waves, but no action potentials. The slow waves are linked to calcium fluxes and both are essential for mechanical activity, i.e. the ASPW. The IAS is pharmacologically characterized by the presence of alpha excitatory and beta inhibitory adrenergic receptors. Cholinergic drugs have an indirect effect through the release of an inhibitory neurotransmitter, very probably VIP, from NANC nerves. The myogenic activity of the IAS is enhanced by its extrinsic sympathetic innervation. Thus, at rest, the IAS is in a state of partial tetanus and contributes approximately 55% of the MABP. Because the IAS ring cannot be completely closed, the anal mucosa and the haemorrhoidal plexuses fill the gap. By compressing these tissues, the IAS perfectly closes the anal canal to retain not only solids but also fluid stool and gas. Acute rectal distension and rectal activity, mainly through intramural pathways, induce reflex IAS relaxation, permitting the rectal contents to be sampled by receptors in the upper anal canal while continence is temporarily maintained by EAS activity and by expansion of the haemorrhoidal cushions. There is a correlation between the volume of rectal distension and the parameters of IAS relaxation. At maximal IAS relaxation, ASPW are absent, indicating the completeness of the inhibition. Although this RAIR is not essential for defecation, insufficient relaxation may be implicated in constipation. Hyperactivity of the IAS resulting in a high MABP and AUSPW has been considered both as a cause and as an effect in haemorrhoids and anal fissure. Continence for fluids and gas is impaired if IAS activity is decreased (i.e. a low MABP), either by direct trauma or by damage of its sympathetic innervation. Severe faecal incontinence will develop when the contractility of both the IAS and the EAS is affected. PMID- 1586770 TI - Advances in the surgical management of anal incontinence. AB - The standard treatments for traumatic and idiopathic faecal incontinence have for the last 10-15 years been sphincter reconstruction and pelvic floor repair, respectively. Results of the treatment of traumatic sphincter lesions have in general been satisfactory, whereas the results after prolonged follow-up of pelvic floor repair for idiopathic anal incontinence seem less convincing. Incontinence due to neurological disorders cannot always be treated by local procedures on the anal sphincter or pelvic floor. This has led to the investigation of a number of other surgical procedures with the aim of re establishing faecal continence. These include transposition of striated muscles, primarily the gracilis and gluteus maximus, implantation of neuromuscular stimulators, implantation of artificial sphincters and implantation of neuroprosthesis. These new techniques, which are also applicable in patients with traumatic and idiopathic anal incontinence where local reconstructive procedures have failed, are reviewed in this chapter in the light of our present state of knowledge. PMID- 1586771 TI - The work of an anorectal physiology laboratory. PMID- 1586772 TI - Anorectal HIV infection and AIDS: diagnosis and management. PMID- 1586774 TI - Leukaemia epidemiology and radiation risks. AB - This review deals with the associations between exposure to ionising and non ionising irradiation and the risks of leukaemia. A systematic approach is adopted to enable the reader to disentangle the different types of exposure and their resultant effects (if any) on leukaemogenesis. PMID- 1586773 TI - The use of radioisotopes in haematology. AB - Radioisotopes used in haematology may be divided into four groups: 1. those used for in vivo studies, involving the labelling of cells in the blood or bone marrow and the use of labelled plasma albumin; 2. investigations involving surface counting over organs such as the bone marrow, spleen, liver and heart; 3. in vitro use of radioisotopes in the haematology laboratory and 4. isotopes used as part of imaging procedures. The shorter the half life of the isotope, the more limited patient exposure to radioactivity will be, but the greater the problems of starting and completing the investigation before the isotope has decayed. Isotopes studies should not be carried out in children or pregnancy unless there are exceptional clinical indications. PMID- 1586775 TI - Therapy of acute myelogenous leukemia. AB - Treatment of acute myelogenous leukemia (AML) is divided into remission induction and post-remission therapy. Remission induction is usually with cytarabine and an anthracycline. Daunorubicin is commonly used but recent data suggest idarubicin or mitoxantrone are equally effective, possibly better. High-dose cytarabine has also been used for remission induction but is not proven superior. Post-remission treatment is typically with two or more courses of drugs similar to those used for remission induction. Other studies use non-cross resistant drugs and/or high dose cytarabine. Although some data favor use of high-dose cytarabine, no approach is clearly superior. There is considerable controversy whether persons in first remission and with an HLA-identical sibling should receive a bone marrow transplant immediately or after relapse. Although transplant results appear superior, especially in persons less than 20 years of age, the most effective strategy may be reserving transplants for persons failing chemotherapy. This strategy also applies to persons receiving autologous transplants or transplants from alternative donors, like HLA-matched related or unrelated persons. PMID- 1586776 TI - Immunological abnormalities in haemophiliacs. AB - 10 years ago, it became apparent that haemophiliacs were developing diseases which were indicative of underlying immunodeficiency. The results of investigation confirmed that many had abnormal immune systems, particularly with regard to cell-mediated immunity. These abnormalities were thought to be a consequence of the use of clotting factor concentrates, and indeed the discovery of HIV and its mode of transmission, confirmed these suspicions. However, it subsequently became clear that HIV infection did not explain all the abnormalities observed. Many in vivo studies have shown that the immune systems of HIV-negative haemophiliacs are not entirely normal, and in vitro studies have shown that clotting factor concentrates per se have a modulating effect on immune function. We have reviewed particularly the abnormalities seen in HIV-negative haemophiliacs and their possible causes, as well as the specific features of HIV infection in haemophiliacs. PMID- 1586777 TI - Platelet antibodies in immune thrombocytopenia. AB - Several tests to detect antibodies to platelets in patients with immune thrombocytopenia have been developed over the 40 years since it was first noted that this disorder was mediated by antiplatelet factors. Early tests were crude and not reproducible. A major landmark was the quantitation of IgG immunoglobulin on platelet membrane and the observation by several workers that marked increases of all classes of immunoglobulin occurred on platelets in patients with immune thrombocytopenia. Although at one time accepted as a diagnostic characteristic of autoimmune thrombocytopenia (AITP), the initial euphoria was tempered over the last decade by the realisation that elevation of platelet associated immunoproteins was not pathognomonic of this disorder and that raised levels were seen in several other disease processes, sometimes even when platelet counts were normal. The nature of these immunoproteins needs careful understanding. True platelet autoantibodies will manifest as increased platelet immunoproteins but not all such platelet proteins are platelet antibodies. There is speculation about the existence and the mode of activity of IgA and IgM immunoglobulins, both commonly found on platelets in AITP. It is sometimes almost inconceivable that the extremely large amounts of PAIgG could possibly represent true autoantibody. Immune complexes are found in plenty in these and other disorders in which thrombocytopenia manifest. In such situations it is likely that 'amplified' immune complexes are bound by Fc receptors, as may be found in viral mediated ITP or in septicaemic states. There is now sound evidence that several glycoprotein such as GP IIb/IIIa, GP Ib, GP V, found on platelet membrane, act as target antigen sites for the attachment of antibodies to platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586778 TI - By their own young hand. PMID- 1586779 TI - Trends in childhood leukaemia in the Nordic countries in relation to fallout from atmospheric nuclear weapons testing. AB - OBJECTIVE: To obtain further information about the risks of childhood leukaemia after exposure to ionising radiation at low doses and low dose rates before or after birth or to the father's testes shortly before conception. DESIGN: Observational study of trends in incidence of childhood leukaemia in relation to estimated radiation exposures due to fallout from atmospheric nuclear weapons testing during the 1950s and 1960s. SETTING: Nordic countries. SUBJECTS: Children aged under 15 years. MAIN OUTCOME MEASURES: Incidence rates of leukaemia by age at diagnosis, sex, country, and calendar year of diagnosis or year of birth; exposure category; relation between leukaemia and exposure for children aged 0-14 and 0-4 separately. RESULTS: During the high fallout period the average estimated dose equivalent to the fetal red bone marrow was around 140 mu Sv and the average annual testicular dose 140 mu Sv. There was little evidence of increased incidence of leukaemia among children born in these years. Doses to the red bone marrow of a child after birth were higher, and during the high exposure period children would have been subjected to an additional dose equivalent of around 1500 mu Sv, similar to doses received by children in several parts of central and eastern Europe owing to the Chernobyl accident and about 50% greater than the annual dose equivalent to the red bone marrow of a child from natural radiation. leukaemia incidence and red marrow dose was not related overall, but rates of leukaemia in the high exposure period were slightly higher than in the surrounding medium exposure period (relative risk for ages 0-14: 1.07, 95% confidence interval 1.00 to 1.14; for ages 0-4: 1.11, 1.00 to 1.24). CONCLUSIONS: Current predicted risks of childhood leukaemia after exposure to radiation are not greatly underestimated for low dose rate exposures. PMID- 1586780 TI - Possible upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. AB - OBJECTIVE: To study the dynamic function of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome. DESIGN: Prospective comparison of patients with postviral fatigue syndrome with two control groups. SETTING: Department of neurology, University of Glasgow, Southern General Hospital; department of psychiatry, St James's Hospital, Dublin. SUBJECTS: 15 patients with postviral fatigue syndrome, 13 age and sex matched healthy subjects, and 13 patients with primary depression. MAIN OUTCOME MEASURES: Serum prolactin concentrations before and one, two, and three hours after administration of buspirone. RESULTS: Because of the effects of sex hormones on prolactin secretion data for men and women were analysed separately. There was no significant difference in baseline prolactin concentrations between patients with postviral fatigue syndrome and healthy subjects or those with primary depression. However, the percentage difference between peak and baseline values was significantly higher in patients with postviral fatigue syndrome than the control groups (one way analysis of variance: women, p = 0.003; men, p = 0.004). CONCLUSIONS: The results suggest upregulation of hypothalamic 5-hydroxytryptamine receptors in patients with postviral fatigue syndrome but not in those with primary depression. The buspirone challenge test may therefore be useful in distinguishing these two conditions. Larger studies are required to explore the potential value of drugs acting on central 5-hydroxytryptamine receptors in the treatment of patients with the postviral fatigue syndrome. PMID- 1586781 TI - Audit of public education campaign to encourage earlier detection of malignant melanoma. AB - OBJECTIVES: To evaluate a public campaign to encourage earlier referral and treatment of primary cutaneous malignant melanoma and thus reduce mortality related to melanoma. DESIGN: Production and distribution of educational material aimed at adults. Update information sent to general practitioners before campaign. Analysis of data on melanoma before and after campaign in June 1985. SETTING: West of Scotland, population 2.7 million. MAIN OUTCOME MEASURES: Total numbers of referrals per month to melanoma clinic, numbers of melanomas diagnosed, change in distribution of thickness, and mortality before and after introducing the campaign. RESULTS: Referrals to the pigmented lesion clinic increased by 278%, from five a week in June-July 1984 to 19 a week in June-July 1985. Twice as many women as men were referred to the clinic (49% of referrals were of women aged under 65). The numbers of newly diagnosed primary cutaneous melanoma were 63 (12/month) in January-May 1985 and 146 (21/month) in June December 1985, an increase of 131%. The percentage of tumours detected that were less than 1.5 mm thick rose significantly by 16% (95% confidence interval 11% to 19%), from 38% (328) in 1979-84 to 54% (592) in 1985-9. Mortality began to fall in women from 1988. CONCLUSIONS: The public education campaign succeeded in reducing the absolute number of thick tumours and melanoma related mortality in women. PMID- 1586782 TI - Randomised controlled trial of cardioprotective diet in patients with recent acute myocardial infarction: results of one year follow up. AB - OBJECTIVE: To test whether a fat reduced diet rich in soluble dietary fibre, antioxidant vitamins, and minerals reduces complications and mortality after acute myocardial infarction. DESIGN: Randomised, single blind, controlled trial. SETTING: Primary and secondary care research centre for patients with myocardial infarction. SUBJECTS: 505 patients with suspected acute myocardial infarction. Those with definite or possible acute myocardial infarction and unstable angina based on World Health Organisation criteria were assigned to diet A (n = 204) or diet B (n = 202) within 24-48 hours of infarction. INTERVENTIONS: Both groups were advised to follow a fat reduced diet. Group A was also advised to eat more fruit, vegetables, nuts, and grain products. MAIN OUTCOME MEASURES: Mortality from cardiac disease and other causes. Serum lipid concentrations and compliance with diet. RESULTS: Blood lipoprotein concentrations and body weight fell significantly in patients in group A compared with those in group B (cholesterol fell by 0.74 mmol/l in group A v 0.32 mmol/l in group B, 95% confidence interval of difference 0.14 to 0.70, and weight by 7.1 v 3.0 kg, 0.52 to 7.68). The incidence of cardiac events was significantly lower in group A than group B (50 v 82 patients, p less than 0.001). Group A also had lower total mortality (21 v 38 died, p less than 0.01) than group B. CONCLUSIONS: Comprehensive dietary changes in conjunction with weight loss immediately after acute myocardial infarction may modulate blood lipoproteins and significantly reduce complications and mortality after one year. PMID- 1586783 TI - Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. AB - OBJECTIVE: To examine whether children of families moving from an area of low incidence of childhood diabetes to one which is higher show a corresponding rise in disease incidence. DESIGN: Disease incidence study over 12 years. SETTING: Bradford District Metropolitan Council area. SUBJECTS: All subjects aged 0-16 years resident within the study area. MAIN OUTCOME MEASURES: The incidences of childhood diabetes in Asian and non-Asian families. RESULTS: The incidence of diabetes in Asian children increased from 3.1/100,000 per year in 1978-81 to 11.7/100,000 per year in 1988-90 (chi 2 for trend = 4.95, df = 1, p = 0.026) whereas that for other children remained constant at 10.5/100,000 per year. Over the entire study period rates were lower in Asian females (4.9/100,000 per year) than in Asian males (8.8/100,000 per year) whereas the reverse was true for other children (males 9.2/100,000 per year; females 12.0/100,000 per year) (test for common odds ratio: chi 2 = 3.81, df = 1, p = 0.052). CONCLUSIONS: Offspring of this transmigratory population had a rising incidence of childhood diabetes which was approaching that of the indigenous population. The data provide strong evidence for an environmental effect in the aetiology of insulin dependent diabetes. PMID- 1586784 TI - Pinpointing clusters of apparently sporadic cases of Legionnaires' disease. AB - OBJECTIVES: To test the hypothesis that many non-outbreak cases of legionnaires' disease are not sporadic and to attempt to pinpoint cases clustering in space and time. DESIGN: Descriptive study of a case series, 1978-86. SETTING: 15 health boards in Scotland. PATIENTS: 203 probable cases of non-outbreak, non-travel, community acquired legionnaires' disease in patients resident in Scotland. MAIN MEASURES: Date of onset of disease and postcode and health board of residence of cases. RESULTS: Space-time clustering was present and numerous groups of cases were identified, all but two being newly recognised. Nine cases occurred during three months within two postcodes in Edinburgh, and an outbreak was probably missed. In several places cases occurred in one area over a prolonged period--for example, nine cases in postcode districts G11.5 and G12.8 in Glasgow during five years (estimated mean annual incidence of community acquired, non-outbreak, non travel legionnaires' disease of 146 per million residents v 4.8 per million for Scotland). Statistical analysis showed that the space time clustering of cases in the Glasgow and Edinburgh areas was unusual (p = 0.036, p = 0.068 respectively). CONCLUSION: Future surveillance requires greater awareness that clusters can be overlooked; case searching whenever a case is identified; collection of complete information particularly of date of onset of the disease and address or postcode; ongoing analysis for space-time clustering; and an accurate yet workable definition of sporadic cases. Other researchers should re-examine their data on apparently sporadic infection. PMID- 1586785 TI - Prevalence of HIV antibody in forensic cases. PMID- 1586786 TI - Psychiatric morbidity and substance abuse among residents of a cold weather shelter. PMID- 1586787 TI - Is duplicate publishing on the increase? PMID- 1586788 TI - Randomised controlled trial of breast shells and Hoffman's exercises for inverted and non-protractile nipples. AB - OBJECTIVE: To determine the value of recommending breast shells or Hoffman's exercises, or both, to pregnant women with inverted or non-protractile nipples who intend to breast feed. DESIGN: Randomised controlled trial with a two treatment by two level factorial design. SETTING: Antenatal clinics in a district general hospital and the community. SUBJECTS: 96 nulliparous women recruited between 25 and 35 completed weeks in a singleton pregnancy with at least one inverted or non-protractile nipple. MAIN OUTCOME MEASURES: Anatomical change of nipples, judged blindly before first breast feeding, and success of breast feeding reported by postal questionnaire six weeks postnatally. RESULTS: Sustained improvement in nipple anatomy was more common in the untreated groups but the differences were not significant (52% (25/48) shells v 60% (29/48) no shells; difference -8% (95% confidence interval -28% to 11%) and 54% (26/48) exercises v 58% (28/48) no exercises; -4% (-24% to 16%)). 24 (50%) women not recommended shells and 14 (29%) recommended shells (21%; 40% to 2%) were breast feeding six weeks after delivery (p = 0.05), reflecting more women recommended shells both deciding to bottle feed before delivery and discontinuing breast feeding. The same number of women in exercise and no exercise groups were successfully breast feeding (0%; -20% to 20%). 13% of women approached about the trial (and planning to breast feed) did not attempt breast feeding. CONCLUSIONS: Recommending nipple preparation with breast shells may reduce the chances of successful breast feeding. While there is no clear evidence that the treatments offered are effective antenatal nipple examination should be abandoned. PMID- 1586789 TI - Developing a hospital information strategy: a clinician's view. PMID- 1586790 TI - The new NHS: first year's experience. West Suffolk: a changing world. PMID- 1586791 TI - Public health heresy: a challenge to the purchasing orthodoxy. PMID- 1586792 TI - ABC of colorectal diseases. Haemorrhoids. PMID- 1586793 TI - Green College Lecture. Ethical challenges in embryo manipulation. PMID- 1586794 TI - Early growth and clotting factors in adult life. PMID- 1586795 TI - Fetal growth and ratio of placental weight to birth weight. PMID- 1586796 TI - Exploding microwaved eggs. PMID- 1586797 TI - Low dose oxybutynin for the unstable bladder. PMID- 1586798 TI - Survival of peripheral intravenous infusions. PMID- 1586799 TI - Monoclonal antibodies in sepsis. PMID- 1586800 TI - Detecting congenital heart disease prenatally. PMID- 1586801 TI - Detecting congenital heart disease prenatally. PMID- 1586802 TI - Melanoma in people aged 65 and over. PMID- 1586803 TI - Notifiable diseases. PMID- 1586804 TI - Notifiable diseases. PMID- 1586805 TI - Maternity services. PMID- 1586806 TI - Maternity services. PMID- 1586807 TI - Maternity services. PMID- 1586808 TI - Preventing coronary heart disease. PMID- 1586809 TI - Photographs misrepresent Romanian health care reforms. PMID- 1586810 TI - Recording HIV status on police computers. PMID- 1586811 TI - Managing infants who cry persistently. PMID- 1586812 TI - Nocturnal asthma. PMID- 1586813 TI - Duplicate publication. PMID- 1586814 TI - In search of the unknown primary. PMID- 1586815 TI - Measuring case mix. PMID- 1586816 TI - Breast feeding in the first six months. PMID- 1586817 TI - Advances in the treatment of chronic heart failure. PMID- 1586818 TI - Joint and limb symptoms in children after immunisation with measles, mumps, and rubella vaccine. AB - OBJECTIVE: To assess whether the combined measles, mumps, and rubella vaccine increases the incidence of joint and limb symptoms in young children. DESIGN: Comparison of six week recalled incidence of symptoms in two groups of children: children who had been immunised at the start of the six weeks, and children eligible for immunisation but who had not received it. SETTING: South Manchester Health Authority. SUBJECTS: 2658 children immunised during July 1989-February 1990 and 2359 not yet immunised. Questionnaires were returned for 1846 immunised children and 1075 not immunised. MAIN OUTCOME MEASURE: Recalled rate of joint and limb episodes determined by postal questionnaire and later by clinical follow up. RESULTS: Compared with non-immunised children the immunised group had an increased incidence of new episodes (relative risk 1.6 (95% confidence interval (1.2 to 2.1)) and first ever episodes, though this was not significant (1.7 (0.3 to 3.5)). The risk of first episodes was increased in girls (3.5 (1.1 to 12.2)) but not in boys (1.0 (0.4 to 2.6)). Similarly, an increased risk was seen in children aged under 5 (12.0 (1.6 to 92.3)) but not in older children (0.7 (0.3 to 1.5)). Most episodes were mild and self limiting, but three immunised children required hospital referral. CONCLUSION: Measles, mumps, and rubella vaccine is associated with an increased risk of episodes of joint and limb symptoms, especially in girls and children under 5. The risk of frank arthritis is substantially less than after wild rubella infection. PMID- 1586819 TI - Life events and breast cancer prognosis. AB - OBJECTIVE: To determine whether psychosocial stress, in the form of adverse life events and social difficulties, depressive illness, or lack of confiding relationships, shortens the postoperative disease free interval in breast cancer patients. DESIGN: Prospective follow up of a cohort of newly diagnosed breast cancer patients for 42 months after primary surgical treatment, using a life events and social difficulties schedule (LEDS) and assessment of depressive symptomatology (DSM-III). SETTING: Patients recruited from breast clinics in Southampton and Portsmouth were interviewed in their homes. PATIENTS: 204 women (83% of 246 consecutive cases) treated either by mastectomy or wide excision followed by radiotherapy interviewed four, 24, and 42 months after operation. MAIN OUTCOME MEASURES: Hazard ratios for relapse of breast cancer in relation to various measures of psychosocial stress. Relapse was defined as local recurrence or distant metastasis, or both, with histological or radiological confirmation and timed from the month when clinical symptoms began. RESULTS: After adjustment for age and axillary lymph node involvement, the hazard ratio associated with severe life events or social difficulties (excluding "own health" ones), or both, during the year before breast cancer surgery was 0.43 (95% confidence interval 0.20 to 0.93); for those during the follow up period it was 0.88 (0.48 to 1.64). For prolonged major depression before surgery and during the follow up period, hazard ratios were 1.26 (0.49 to 3.26) and 0.85 (0.41 to 1.79) respectively. For absence of a full confidant the figures were 0.93 (0.42 to 2.09) and 0.86 (0.38 to 1.93). CONCLUSION: These results give no support to the theory that psychosocial stress contributes to relapse of breast cancer. PMID- 1586820 TI - Prevalence of HIV among childbearing women and women having termination of pregnancy: multidisciplinary steering group study. AB - OBJECTIVE: To determine the prevalence of HIV among pregnant women, in particular those whose behaviour or that of their partners put them at "low risk" of infection. DESIGN: Voluntary named or anonymous HIV testing of pregnant women during 21 months (November 1988 to July 1990). SUBJECTS AND SETTING: All women who planned to continue their pregnancy and attended clinics serving the antenatal populations of Edinburgh and Dundee. All women admitted for termination of pregnancy to gynaecology wards serving the pregnant populations of Dundee and outlying rural areas. MAIN OUTCOME MEASURES: Period prevalence of HIV antibody positivity. RESULTS: 91% of antenatal clinic attenders and 97% of women having termination of pregnancy agreed to HIV testing on a named or anonymous basis. HIV period prevalences for antenatal clinic attenders and women having termination of pregnancy tested in Dundee were 0.13% and 0.85% respectively, and for antenatal clinic attenders tested in Edinburgh 0.26%. For those at "low risk" rates for antenatal clinic attenders and women having termination of pregnancy in Dundee were 0.11% and 0.13%, and for antenatal clinic attenders in Edinburgh 0.02%. In Dundee HIV prevalence among women having a termination of pregnancy (0.85%) was significantly greater than that among antenatal clinic attenders (0.13%). CONCLUSIONS: HIV infection is undoubtedly occurring among women at "low risk," and it is clear that a policy of selective testing of those at only "high risk" is inadequate for pregnant women living in areas of high prevalence such as Edinburgh and Dundee. Moreover, when studying pregnant populations in such areas there is the need to include those having a termination of pregnancy. PMID- 1586822 TI - Reliability of video taped interviews with children suspected of being sexually abused. AB - OBJECTIVE: To determine the reliability of judgments about the likelihood of child sexual abuse based only on video recorded interviews. DESIGN: Blinded rating of likelihood of abuse by seven professional groups and comparison with consensus rating. SETTING: Child and adolescent psychiatry centre. SUBJECTS: Four people from each of seven professional disciplines: specialist psychiatrists, general psychiatrists, experimental psychologists, trainee social workers, trainee clinical psychologists, lawyers, and police. MAIN OUTCOME MEASURE: Rating of 12 recorded interviews. RESULTS: Agreement between the consensus panel and professional groups was 83% (151/183) for high likelihood cases (seven cases) and 89% (118/132) for low likelihood cases (five). Specialist psychiatrists and the police were better able to identify high likelihood cases than were other groups with less experience of interviewing sexually abused children (91% (48/53) v 79% (102/129); p = 0.05). CONCLUSIONS: Raters could accurately distinguish children with low likelihood of abuse on interview evidence alone, but those with more experience of dealing with sexual abuse were better at identifying high likelihood cases. PMID- 1586821 TI - The Bradford community stroke trial: results at six months. AB - OBJECTIVE: Comparison of day hospital attendance and home physiotherapy for stroke patients leaving hospital to determine which service produces greater functional and social improvement for the patient, reduces emotional stress for the care giver, and lessens the need for community support. DESIGN: Stratified, randomised trial of stroke patients attending day hospital two days a week or receiving home treatment from a community physiotherapist. The six month assessment results are reported in this paper. SUBJECTS: Patients over 60 years old resident within the Bradford metropolitan district discharged home after a new stroke with residual disability. SETTING: Four day hospitals in two health authorities and domiciliary work undertaken by experienced community physiotherapists. MAIN OUTCOME MEASURES: Barthel index, functional ambulatory categories, Motor Club assessment, Frenchay activities index, and Nottingham health profile were used. Carers' stress was indicated by the general health questionnaire. Treatment given and community care provided were recorded. RESULTS: Of 124 patients recruited, 108 were available for reassessment at six months. Both treatment groups had significantly improved in functional abilities between discharge and six months. The improvements were significantly greater for patients treated at home (Mann-Whitney test; Barthel index, median difference 2 (95% confidence interval 0 to 3) p = 0.01; Motor Club assessment, median difference 2 (1 to 5), p = 0.01). The home treated patients received less treatment (median difference 16 (11 to 21) treatments, p less than 0.001). More than a third of patients in both groups showed depressed mood, and a quarter of care givers were emotionally distressed. CONCLUSIONS: Home physiotherapy seems to be slightly more effective and more resource efficient than day hospital attendance and should be the preferred rehabilitation method for aftercare of stroke patients. New strategies are needed to address psychosocial function for both patients and care givers. PMID- 1586823 TI - Validation of medical history taking as part of a population based survey in subjects aged 85 and over. PMID- 1586824 TI - Does a truss benefit a patient with inguinal hernia? PMID- 1586825 TI - Effect of feedback on test ordering behaviour of general practitioners. AB - OBJECTIVE: To assess the effect of feedback on the test ordering behaviour of general practitioners. DESIGN: Comparison of requests at two diagnostic centres, and internal comparison between tests which were discussed in feedback and tests which were not. SETTING: A diagnostic centre in Maastricht giving feedback and another elsewhere in the Netherlands (laboratory A) not giving feedback. SUBJECTS: All 85 general practitioners in the region of Maastricht, and all general practitioners in the region of laboratory A. MAIN OUTCOME MEASURES: Numbers of tests requested by general practitioners. RESULTS: Requests at the Maastricht diagnostic centre decreased soon after the onset of feedback whereas there was a persistent increase in requests at laboratory A. Tests that were discussed showed the strongest decrease (maximum 40%), though tests that were not discussed decreased as well (maximum 27%). CONCLUSIONS: Feedback on diagnostic requests may exert a strong influence on request behaviour. Four years after the onset of feedback the effects were still noticeable. PMID- 1586826 TI - ABC of colorectal diseases. Anatomy and physiology of the colon, rectum, and anus. PMID- 1586827 TI - The new NHS: first year's experience. East Birmingham: the beast was fed. PMID- 1586828 TI - Solving the problems with patient controlled analgesia. PMID- 1586829 TI - Solving the problems with patient controlled analgesia. PMID- 1586830 TI - Intussusception in infants. PMID- 1586831 TI - Effect of overdose of trazodone. PMID- 1586832 TI - Intussusception in infants. PMID- 1586833 TI - The fast of Ramadan. PMID- 1586834 TI - Advanced trauma life support courses. PMID- 1586835 TI - Data on vaccine uptake should be checked. PMID- 1586836 TI - Modular contracts for general practitioners. PMID- 1586837 TI - Predictors of general practitioners' workload. PMID- 1586838 TI - Doctors and the control of major releases of chemicals. PMID- 1586839 TI - Economics and the fundamental principles of the NHS. PMID- 1586840 TI - Weightings used in distributing NHS resources. PMID- 1586841 TI - Ban on home HIV tests is unjustified. PMID- 1586842 TI - Costs of day case surgery. PMID- 1586843 TI - Workload in general practice under the new contract. PMID- 1586844 TI - Hearing impairments in middle age: the acceptability, benefit and cost of detection (ABCD). AB - The major epidemiological investigations of hearing impairment, disability and handicap show that the elderly are the group most disabled by their hearing impairment. There is considerable debate concerning the most efficient way of reducing this inevitable burden of age-related hearing impairments in the next generation. Early fitting of 'targeted' individuals with hearing aids may help but there are a large number of methodological problems associated with conducting and evaluating such a programme of research (especially retrospectively). The logical prerequisite to early fitting as a means of reducing later disability is to ascertain the acceptability of and benefit given by intervention at this early stage. This study therefore set out to investigate the age/sex register provided by the primary physician (GP) as an appropriate base to identify candidates for early aid fitting among a sample of middle-aged patients (50-65 years) living in Roath, Cardiff. Of the 662 who replied to an initial contact letter (1050 were on the age/sex register), 21 already possessed hearing aids. After screening and examination 66 people were offered some form of management which was accepted by 43 during the course of the study. Aid use thereby increased from about 3% to over 9% in this middle-aged group. A 2 year follow-up indicated continued use of the aids, and benefit on a speech reception task was measured. The cost of detecting those who might benefit was calculated using a two-question 'paper and pencil' screen as the first step. A national programme for Wales would cost at least 188,000 pounds per annum at 1990 prices over an initial 5 year span if a criterion which aimed to find at least 45 dB HTL impairments over mid-frequencies was implemented. For a criterion of 35 dB the cost would be 378,000 pounds pa. PMID- 1586845 TI - Frequency selectivity as a potential measure of noise damage susceptibility. AB - The notched-noise procedure of Patterson (1974, Journal of the Accoustical Society of America, 55, 802-809; 1976, Journal of the Acoustical Society of America, 59, 640-654) was employed in revealing changes in auditory frequency selectivity (FS) in noise-exposed industrial workers in manufacturing plants in which noise levels in the working environment exceeded 90 dB(A). With 4 kHz as the test frequency, both threshold and FS measures were applied to three groups of non-exposed young adults (total N = 61) for reference values and to workers in three different factories, some ('noise-exposed') working in noise levels over 90 dB(A) (total N = 222). In another study involving 185 workers only the FS test was repeated after a work session, and the results are reported on 31 who worked in high noise levels. Pre-work-shift data showed that when thresholds were better than 30-dB HL most FS values were 10 dB or more, while subjects with hearing threshold levels beyond that showed reduced FS. Two post-work-shift studies of 144 ears of the noise-exposed workers showed significant deleterious changes in both thresholds and FS but the relationships were different in the two studies. The findings indicate that the notched-noise test is sensitive to noise-induced auditory damage, even after a single work-shift. Attractive features of the procedure are that it reduces the need for a quiet test environment and that it can be more resistant to testee manipulation or threshold 'learning' effects, often seen in industrial audiometric testing. PMID- 1586846 TI - Threshold of hearing (0.125-20 kHz) in children and youngsters. AB - Pure-tone air-conduction audiometry has been performed in three groups of children and youngsters aged 10, 14 and 18 years old. The complete frequency range of 0.125 to 20 kHz was measured, and number of different questions were raised. Firstly, the hearing threshold in the conventional frequency range was compared to the international standard ISO 389. Significant differences from ISO zero were found for all groups and at all frequencies of 0.125 to 8 kHz. Secondly, possible noise damage, shown as dips in the audiograms at 3, 4 or 6 kHz was examined; and thirdly, high-frequency (8-20 kHz) sensitivity between groups was compared. Only a few audiograms, the majority being in the youngest age group, were found to be a result of possible noise damage, and in the extra-high frequency range, a systematic decrease in sensitivity was found for the two older groups compared to the 10-year-old children at frequencies higher than 14 kHz. PMID- 1586847 TI - A clinical test battery for obscure auditory dysfunction (OAD): development, selection and use of tests. AB - Obscure auditory dysfunction (OAD) is defined as convincing self-report of auditory disability accompanied by normal pure-tone thresholds. This has been increasingly recognized as a clinical problem, but until now there has not been a standard clinical procedure for dealing with such patients. This paper summarizes a demographic and clinical characterization of a sample of 50 OAD patients, reports new norms on the tests in the version issued, and describes a test package developed from a case-control research study that can be routinely used with OAD patients. The package enables clinicians: (i) to confirm, or otherwise, OAD as the appropriate classification for individuals presenting with OAD-like symptoms; (ii) to elucidate the underlying basis of OAD in such individuals and hence in most cases to provide explanations that are justified by test findings; and (iii) to counsel cases in a fashion appropriate for each individual. The package consists of four performance tests, a specialized clinical interview and a brief questionnaire to determine the severity of OAD. The assessment takes approximately 37 min and can be run using a two-channel audiometer and a cassette recorder. PMID- 1586848 TI - Background noise in rooms used for pure-tone audiometry in disability assessment. AB - Background noise limits for audiometry are determined by the effects of masking and are specified in international standards. The standards provide for audiometric testing over a range of audiometric frequencies extending down to 500 Hz or lower. The lowest frequency of testing is an important factor determining the admissible noise, and for certain applications it is appropriate to consider the limits applicable to testing over a more restricted range. Assessment of hearing disability in the UK is generally based on a consideration of pure-tone hearing threshold levels in the frequency range 1 kHz upwards. A modification of the standardized noise limits is proposed which allows some relaxation appropriate to this higher minimum frequency. For air-conduction audiometry, these modifications affect only the permissible background noise in the frequency range below 1 kHz. Where bone-conduction audiometry is required in order to quantify a conductive component of the hearing loss, the measurements need to be made on both ears with the non-test ear masked in both cases; the external background noise will thus only be heard monaurally and this justifies a correction to the noise limits compared with those appropriate to bone-conduction audiometry without masking. PMID- 1586849 TI - Do induction loops pose a hazard to health? AB - The RNID actively promotes the use of induction loops as a means of improving communication using hearing aids, particularly in public places. The magnetic flux density, 100-500 nT, needed for effective performance is comparable with fields to which people are exposed every day in the home, and much less than those which can be encountered in the work environment. In the light of current scientific knowledge, the risks to health would appear to be minimal. PMID- 1586850 TI - Consequences of the change to standards for air-conduction hearing levels. A cautionary note. AB - The issue of BS 2497 Parts 5 and 6 in 1988 brought British Standards into line with the latest revisions to ISO 389. As a consequence, many audiometers that were previously calibrated using a 9-A coupler will now have to be calibrated with an artificial ear. Whilst this may appear to be a seemless change involving merely alterations to measurement apparatus, this technical note illustrates for two earphone types that it entails a shift in the Hearing Level standard by a maximum of 3 dB at 2 kHz. This has ramifications for longitudinal studies of hearing and for monitoring of hearing threshold levels in persons exposed to noise. PMID- 1586851 TI - Romanian hearing impaired children, British Red Cross Royal National Institute for the Deaf Project. PMID- 1586852 TI - A survey of 'tinnitus clinics' in NHS hospitals. PMID- 1586853 TI - Relationship between hearing threshold level and its component parts. PMID- 1586854 TI - Access to health care: UNY Care and universal health insurance. PMID- 1586855 TI - Primary care: graduate medical education. PMID- 1586856 TI - Dr. David Axelrod and the Health of the Public: Looking Ahead. Address. PMID- 1586857 TI - Public health initiatives: environmental health. PMID- 1586858 TI - Prevention and promotion. PMID- 1586859 TI - Quality of health care and costs: standards, outcome, and regulation. PMID- 1586860 TI - Medical malpractice. PMID- 1586861 TI - Ethics, choice, and policy. PMID- 1586862 TI - Collegiality in history. PMID- 1586863 TI - Collegiality: what is it? AB - The privileges of members of the academic medical collegium consist of the following: freedom to pursue medical knowledge, performance of therapeutic interventions, opportunity to instruct, freedom to engage in experimentation, and to share in the expression and communication of medical knowledge with colleagues. The obligations are the same as those of the purely academic collegium mentioned above. Additionally, there are the obligations specific to the medical collegium: the care and cure of the sick, fulfillment of the moral covenant to the patient, to guarantee the life cycle of medical ideas, to assure academic critique in medicine, the stewardship of medical knowledge, and adherence to a professional code. We feel that the relationship among medical colleagues adheres to a codified set of duties, one that can be objectively relied upon to protect the endangered species of American academic medicine, the collegial environment. PMID- 1586864 TI - The advantages of collegiality. PMID- 1586865 TI - Obstacles to collegiality in the academic health center. PMID- 1586866 TI - Maintenance of collegiality. PMID- 1586867 TI - Collegiality: implications for the future. PMID- 1586868 TI - Mechanical exsufflation, noninvasive ventilation, and new strategies for pulmonary rehabilitation and sleep disordered breathing. AB - Manual and mechanical exsufflation are important but underutilized ways to clear airway secretions. These methods are especially useful when used in concert with noninvasive intermittent positive airway pressure ventilatory assistance to facilitate extubation and ventilator weaning. This can be used as much as 24 hours a day as an alternative to tracheostomy ventilation or body ventilator use for patients with paralytic restrictive ventilatory insufficiency. These techniques expedite community management of ventilator assisted individuals by avoiding tracheostomy and need for invasive suctioning and ongoing wound care. For these techniques to be effective and to prevent further suppression of ventilatory drive, supplemental oxygen administration must be avoided unless pO2 is less than 60 mm Hg despite normalization of pCO2. Custom molded interfaces for the delivery of noninvasive intermittent positive airway pressure ventilatory assistance can also be used to facilitate the delivery of variable inspiratory expiratory positive airway pressure for patients with obstructive sleep apnea. Noninvasive intermittent positive airway pressure ventilatory assistance or body ventilator use can rest the respiratory muscles of patients with advanced chronic obstructive pulmonary disease. This and pulmonary rehabilitation programs geared to exercise reconditioning are therapeutic options that significantly improve the quality of life of these patients. For both paralytic restrictive and obstructive pulmonary patients, these techniques decrease cost and frequency of hospitalizations. PMID- 1586869 TI - Hyperthermia in cancer therapy: where are we today and where are we going? PMID- 1586871 TI - Mechanism of glucocorticoid action in asthma: too little, too late. PMID- 1586870 TI - Functional electrical stimulation and suppression of spasticity following spinal cord injury. PMID- 1586872 TI - Basophil migration and chemotaxis. PMID- 1586873 TI - Viruses as precipitants of asthma symptoms. I. Epidemiology. AB - The epidemiological studies cited have indicated that viruses are commonly associated with wheezing illnesses in populations, in individuals, and in time, but, unlike bacteria, are rarely found during asymptomatic periods. Viruses have been identified in up to 50% of wheezing illnesses and asthma exacerbations occurring in childhood, and in up to 20% of those in adults. In childhood the predominant organisms identified have been rhinoviruses. RSV and parainfluenza viruses, but coronaviruses have not been studied adequately. Wheezing appears to be more common during rhinovirus and RSV than other virus infections in children spontaneously presenting with respiratory infections to medical care, but all virus groups have been incriminated, and in general, wheezing occurs in upwards of 50% of viral infections in asthmatics followed prospectively. The few adult studies available show little difference between viruses in identification rates during wheezing, or propensity to result in wheezing. The predominant viruses change with age, and children with asthma seem to be more prone to symptomatic virus infections than other children, although the presence of atopy alone does not appear to be important. There are important gaps in our knowledge of the epidemiology of virus-associated wheezing attacks, and further prospective studies are required, using early investigation and sensitive methods for identifying rhinoviruses and coronaviruses, to study severe asthma in children and adults. It is hoped that the use of nucleic acid hybridization and newer antigen-detection techniques will improve the ability to identify difficult viruses such as coronaviruses and rhinoviruses in the future. The ability to identify subclinical infections and compare the ratio of subclinical to clinical infections in normal and asthmatic children would be useful but would require intense monitoring of both groups for an extended period (minimum 12 months to cover seasonal variation) with full virological studies every 2-4 weeks-a difficult and expensive task. Another important line of study would be to prospectively document indoor aeroallergen exposure and virus infections in the same individuals, and compare their importance as precipitants of acute severe asthma attacks. With a clearer understanding of the groups at risk for asthma attacks, and the factors which put them at risk and precipitate their attacks, effective preventive strategies will become more feasible. PMID- 1586874 TI - The migration of eosinophils into the sputum of asthmatics: the role of adhesion molecules. PMID- 1586875 TI - Polymyxin B-induced bronchial neutrophilia does not alter airway responsiveness to methacholine in cynomolgus monkeys. AB - The purpose of this study was to develop a primate model of chronic bronchial neutrophilia to investigate the role of neutrophils in the pathogenesis of airway hyperresponsiveness. Ten adult male cynomolgus monkeys (Macaca fascicularis) were anaesthetized and intubated for each study. Six animals each received a total of seven inhalation treatments with polymyxin B (200 micrograms) over a 24 day period. Four control animals received an identical treatment regime with vehicle inhalations. Airway cellular composition was assessed by bronchoalveolar lavage (BAL). Airway responsiveness was assessed by methacholine cumulative dose response determinations. There were no significant changes in airway cellular composition or airway responsiveness in the control group. In contrast, Polymyxin B inhalation resulted in an influx of neutrophils (PMN) into the lungs which peaked at day 10 of the study (%PMN in BAL fluid rose from 5 +/- 2 to 51 +/- 8, P less than 0.001) and persisted out to day 24 (41 +/- 8, P less than 0.01). Increases in PMNs were associated with an increase in BAL levels of myeloperoxidase (MPO levels in BAL fluid increased from 2 +/- 3 to 180 +/- 23 OD P less than 0.05). Although airway PMN percentages and MPO concentrations were chronically elevated, airway responsiveness did not change. These results suggest that the neutrophil does not play a functional role in the onset of hyperresponsive airways in primates. PMID- 1586876 TI - Effect of corticosteroid treatment on interleukin-1 and tumour necrosis factor secretion by monocytes from subjects with asthma. AB - Peripheral blood monocytes (PBM) may be activated in asthmatic patients, a condition usually reverted by corticosteroid (CS) treatment. In the present research we have evaluated the spontaneous or lipopolysaccharide (LPS)-induced production of interleukin 1 (IL-1) and tumour necrosis factor (TNF) by PBM obtained from 14 asthmatic subjects during an asthmatic attack and after 1 week of CS treatment. The control group included 20 healthy volunteers. PBM obtained during severe asthma showed a pattern of IL-1 and TNF secretion similar to that of normal subjects. After CS treatment, IL-1 levels did not change significantly in comparison to baseline values, while LPS-induced TNF production was apparently related to the degree of airway obstruction after CS treatment. In fact, TNF production by PBM from CS-responsive subjects was significantly decreased in comparison to the levels determined before CS treatment, while PBM from CS resistant subjects produced the same cytokine levels regardless of CS treatment. The present study suggests that the determination of LPS-induced TNF secretion by PBM could be used to confirm the effectiveness of CS treatment in asthma. PMID- 1586877 TI - Haemopoietic growth factors induce human basophil migration in vitro. AB - Accumulation of basophils in inflammatory sites is an important aspect of the late-phase allergic reaction involving skin and upper and lower airways, suggesting the existence of mechanisms for basophil migration. Because haemopoietic growth factors have been shown to stimulate various functions of human basophils, we tested the ability of haemopoietic growth factors to migrate basophils in vitro. Both IL-3 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induced migration of purified normal basophils (purity c. 80%) in a dose-dependent fashion at picomolar concentrations, while granulocyte (G)-CSF, macrophage (M)-CSF, and IL-4 had no effect at all. Chequerboard analyses indicate that migratory activity of both factors are chemokinetic. These results suggest that local production of both factors during allergic reactions might potentially play an initial role in the recruitment of basophils from the circulation to sites of inflammatory reactions. PMID- 1586878 TI - Topical vasoconstrictor (oxymetazoline) does not affect histamine-induced mucosal exudation of plasma in human nasal airways. AB - Mucosal exudation of almost unfiltered plasma proteins, plasma-derived mediators and fluid has recently been advanced as a major respiratory defence mechanism. Oxymetazoline chloride is a commonly used decongestant agent. By reducing blood flow it may reduce mucosal exudation and thus compromise the mucosal defence capacity. This study examines the effect of topically applied oxymetazoline on histamine-induced plasma exudation into human nasal airways. Twelve normal volunteers participated in a double-blind, randomized, cross-over and placebo controlled study with pretreatment with a single dose oxymetazoline chloride (5 micrograms or 50 micrograms; a dose previously known to reduce nasal mucosal blood flow by almost 50%) prior to the histamine challenge sequence. Nasal lavages were performed every 10 min for 140 min, and three histamine challenges were performed at 30-min intervals during this period. The concentrations of two exudative indices, N-alpha-tosyl-L-arginine methyl ester (TAME)-esterase activity and albumin, were measured in the nasal lavage fluids. Nasal symptoms (sneezing, nasal secretion and blockage) were assessed by a scoring technique. Histamine induced all three symptoms with correlatively raised levels of the biochemical markers for plasma exudation. Oxymetazoline chloride caused a significant decrease in nasal stuffiness, but did not influence the other nasal symptoms or the histamine-induced plasma exudation. It is concluded that histamine-induced plasma exudation is not influenced by topical oxymetazoline. Thus, an important airway defence reaction such as plasma exudation may be little affected by topical alpha-adrenoreceptor-mediated vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586879 TI - Type I allergy induced by Limulus Amoebocyte Lysate (LAL). AB - During the last few years Limulus Amoebocyte Lysate (LAL) has been extensively used to detect minimal amounts of endotoxins of Gram-negative bacteria in products of the pharmaceutical industry, in food stuff, body fluids, house dust and room air. LAL is produced from cells of the haemolymph (amoebocytes) of the horseshoe crab (Limulus polyphemus), which respond with an extremely sensitive clotting system upon contact with endotoxins. In this study we demonstrate by typical case history, positive skin test and ELISA the occurrence of Type I allergy to LAL in a patient suffering from conjunctivitis and rhinitis at work. PMID- 1586880 TI - Nucleofractis phacoemulsification through a small pupil. AB - A small pupil is an added risk with any technique for cataract extraction. A prospective study involving 1880 consecutive cataract procedures performed by one surgeon between January and June 1990 was carried out to determine the incidence of small pupils (preoperative diameter of 4 mm or less) and the surgical risk with phacoemulsification and implantation of an intraocular lens (IOL) "in the bag." Thirty eyes (1.6%) were found to have a small pupil. All 30 eyes received an in-the-bag posterior chamber IOL, with no intraoperative complications such as anterior or posterior capsule tears. The need for iris-enlarging surgery was correlated with pupil size: such surgery was done in O of the 10 eyes with pupils measuring 4 mm, 1 of the 12 eyes with pupils measuring 3 to 3.5 mm and 4 of the 8 eyes with pupils measuring 2 to 2.5 mm. The author proposes that opening the capsule with a continuous tear and removing the cataract by means of phacoemulsification with nuclear fracturing (nucleofractis) constitutes safe, efficient surgical management of eyes with small pupils undergoing cataract extraction. PMID- 1586881 TI - Cataract extraction in uveitis: comparison of aphakia and posterior chamber lens implantation. AB - We reviewed the charts of 39 patients (45 eyes) with uveitis who underwent cataract extraction (intracapsular or extracapsular) with or without implantation of a posterior chamber intraocular lens (IOL) at the Royal Victoria Hospital, Montreal, between 1981 and 1990. The nine eyes with Fuchs' iridocyclitis in which an IOL was implanted had good visual results and few postoperative complications. The 18 eyes with uveitis other than Fuchs' iridocyclitis that received an IOL did not show a greater risk of postoperative complications than those left aphakic (n = 17), and the postoperative visual acuity was comparable to that of the aphakic eyes. Although the numbers are small, we conclude that the presence of uveitis does not automatically exclude posterior chamber pseudophakia. PMID- 1586882 TI - Effects of Healon vs. Viscoat on endothelial cell count and morphology after phacoemulsification and posterior chamber lens implantation. AB - The endothelial cell count and several morphologic characteristics of the cells were examined before and after surgery in 56 consecutive patients (60 eyes) who underwent phacoemulsification and implantation of a posterior chamber intraocular lens with either Healon (30 eyes) or Viscoat (30 eyes) as the viscoelastic material. In all cases the technique was the same, including removal of the viscoelastic from the anterior chamber at the end of the operation. The mean cell loss was greater in the Viscoat group than in the Healon group (9.27% +/- 2.52% vs. 2.71% +/- 2.53%), but not significantly so. There was a significantly greater reduction in polymegathism in the Healon group than in the Viscoat group (p less than 0.05). Although the results suggest that Healon has a greater protective effect on the corneal endothelium than Viscoat, the greater effort needed to remove Viscoat from the anterior chamber may have adversely affected the endothelium. Further studies in which Viscoat is left in the eye are warranted. PMID- 1586883 TI - Modifications to the semicircular flap technique in eyelid reconstruction. AB - The most common reconstructive procedure in the upper and lower eyelid is direct closure of the lid margin. When additional mobilization of tissue is needed to close a defect, lateral canthotomy and cantholysis is suggested. Mobilization of tissue beyond the lateral orbital rim is occasionally required. We have found that in the lower eyelid the mobilized tissue is much better supported if the initial incision is made vertically toward the eyebrow rather than temporally, as is suggested with the semicircular flap technique. We describe modifications to this technique, which we refer to as the vertical-temporal advancement flap, and present the results in 28 consecutive patients followed for 8 months to 3 years. PMID- 1586884 TI - Improvement of contrast sensitivity with yellow filter glasses. AB - Yellow filter glasses, often sold as "antifog" or "safety" glasses at department stores and other retail outlets, are claimed to improve contrast sensitivity and the yield of visually perceived objects, particularly under poor conditions (e.g., fog, rain and twilight), by enhancing contrast. These claims were tested in 15 healthy subjects (30 eyes) aged 26 to 58 (mean 42.5) years with the Vision Contrast Test System (VCTS 6500), first with and then without yellow filter glasses. Testing was done with commercial antifog glasses and frame-mounted, hand held filter glasses of CR (Columbia resin) 39 quality with a yellow tint made by an optician. Contrast sensitivity was found to be significantly improved with yellow filter glasses (p less than 0.0001). The use of yellow filter glasses may safely be recommended to patients who report subjective improvement in contrast vision with such glasses. PMID- 1586885 TI - Orbital hemorrhage during dacryocystorhinostomy. AB - Orbital hemorrhage during dacryocystorhinostomy (DCR) is a very rare but potentially devastating complication of this procedure. It is probably due to trauma to the anterior ethmoidal artery, which has a variable course and may have branches close to or in the surgical site. Increasing resistance to retropulsion of the globe is an important sign of orbital hemorrhage. If the hemorrhage does not resolve spontaneously, direct decompression of the blood within the orbit is necessary. The authors review their experience with this complication of DCR. PMID- 1586886 TI - Endogenous Klebsiella pneumoniae endophthalmitis in diabetic patients. AB - We describe 12 patients with endogenous endophthalmitis caused by Klebsiella pneumoniae seen between 1983 and 1988. Three patients had bilateral involvement. Eleven patients had diabetes mellitus, either newly diagnosed or poorly controlled. In six cases the infection was associated with a liver abscess. In all eyes the outcome was light perception or worse; nine eyes had no light perception. Six eyes were enucleated or eviscerated. PMID- 1586887 TI - Low-dose tamoxifen retinopathy. AB - A 68-year-old woman with metastatic breast carcinoma manifested bilateral tamoxifen-induced retinopathy after 9 years of low-dose therapy. Treatment with the drug was stopped, with partial resolution of the retinopathy and improvement in visual acuity over 2 1/2 years of follow-up. PMID- 1586888 TI - Thyroid hormone balance in beluga whales, Delphinapterus leucas: dynamics after capture and influence of thyrotropin. AB - Ten beluga whales, Delphinapterus leucas, were captured in the Churchill River, Manitoba, held for up to five days, and then released. Blood samples were obtained immediately after capture and at 6-7 h intervals thereafter to monitor changes in circulating levels of thyroid hormones (TH). In six of the whales, total and free thyroxine (T4) and triiodothyronine (T3) declined steadily, whereas reverse-T3 (rT3) showed a transient increase during the first 24-36 h, followed by a decrease to below initial values. The changes in TH may have been due to glucocorticoid-mediated reduction in endogenous thyroid stimulating hormone (TSH), and inhibition of 5'-monodeiodinase in peripheral tissue. Two whales were given 10 IU of bovine TSH immediately after capture, and again one and two days later, resulting in successive increases in all TH, which remained elevated for at least 24 h after the last injection. Thereafter, circulating levels declined as in the untreated whales. Two whales receiving a single TSH injection on the fourth day responded with an increase in plasma TH comparable to that observed following the first TSH injection in the other two animals. Average (+/- SD) circulating level of rT3 at capture was 6.3 +/- 3.1 nmol/L, which is higher than reported for any other mammal and was significantly correlated with the naturally elevated levels of T4 that occur in belugas occupying estuaries during the summer. PMID- 1586889 TI - Clinical and immunological effects of single bolus administration of recombinant interleukin-2 in cattle. AB - Recombinant bovine interleukin-2 (rBoIL-2) was administered as a single intramuscular bolus to healthy calves to determine the minimal dose capable of exerting a biological response. Doses ranging from 2.5 to 0.05 micrograms rBoIL 2/kg did not induce pyrexia, diarrhea, or depression, nor did they alter any blood chemistry or hematological parameters commonly associated with IL-2 toxicity. Moreover, the only significant immunological change observed was a reduction in the number of peripheral blood lymphocytes identified with the monoclonal antibodies B7A, BAQ4A (WC1+ cells), CACTB6A (WC2+ cells) and DH59B (monocytes). The decrease in cells associated with these markers did not influence non-MHC restricted cytotoxicity or in vitro lymphocyte proliferative responses to mitogens and IL-2. The treatments had no effect on delayed type hypersensitivity responses to phytohemagglutinin. These results indicate that IL 2 may be involved in the regulation of trafficking patterns of a unique subpopulation of lymphocytes in cattle. PMID- 1586890 TI - Physiological and morphological changes in bovine mammary glands following intramammary infusion of recombinant interferon-gamma. AB - Eleven lactating dairy cows were used to evaluate the response of bovine mammary glands to increasing doses of recombinant bovine interferon (rBoIFN)-gamma. Right front and rear quarters were intramammarily infused with eight different doses (10(2) U to 2 x 10(8) U/quarter) of rBoIFN-gamma; each dose was tested in at least two quarters. Left udder halves served as within animal controls in which quarters were injected with a saline placebo or were not infused at all. Milk secretion samples for compositional analysis were collected from each quarter prior to infusion and at 6, 24, 36 and 48 h following infusion. Animals were slaughtered immediately following the 48 h sampling period and mammary tissue was obtained for morphometric analyses. Milk composition was similar between control quarters and those quarters infused with up to 10(5) U of rBo-IFN-gamma during the entire sampling period. Quarters infused with 10(6) U and 10(7) U of rBoIFN gamma had higher milk somatic cell counts (SCC) following treatment compared with preinfusion values. Changes in the composition of mammary secretion were most dramatic in quarters infused with greater than or equal to 10(8) U of rBoIFN gamma as indicated by the significant increase in SCC and milk pH with a concomitant decrease in lactose concentration when compared with pre-infusion values or with control quarters. Morphometric analysis of tissue demonstrated an increase in stroma, a decrease in luminal area, and a marked increase in the number of infiltrating leukocytes in those quarters infused with the higher doses of rBoIFN-gamma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586891 TI - Studies on the stability of a human adenovirus-rabies recombinant vaccine. AB - Human adenovirus type 5 containing the rabies virus glycoprotein gene (rHAd-RG1) has potential for the oral vaccination of animals. The stability of this recombinant was tested indoors and outdoors by measuring the loss in virus infectivity. Under indoor conditions the stability of the recombinant virus was studied in an egg yolk-containing commercial stabilizer and a simple buffered salt solution (EBSS; Earle's balanced salt solution) at 4 degrees C and room temperature (24-25 degrees C). Over 16 days, there was a more rapid loss in virus titer at room temperature than at 4 degrees C in both suspending media; however, these differences were slight and may be significant when the overall stability of the vaccine is considered. When the virus was mixed with either 10% (w/v) fox or skunk feces or EBSS, placed on stainless steel disks and the disks kept under ambient conditions (air temperature 24-25 degrees C; relative humidity 45-50%), there was a more rapid decline in virus titer in the fecal suspensions (3% remained after 72 h) than in EBSS (26% remained after 72 h). When bait-coated blister packs of the vaccine were placed in an outdoor location in the fall (October) season, there was a larger drop in the virus titer for vaccines placed in the sun (54% over 32 days) than for those in the shade (40% over 32 days). Incorporating proteinaceous stabilizers in the vaccine samples for outdoor study showed virus stability was not enhanced in their presence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1586892 TI - Ultrastructural and transmission evidence of Sarcocystis cruzi associated with eosinophilic myositis in cattle. AB - Skeletal muscle, diaphragm, tongue, esophagus and heart of beef carcasses that were condemned for eosinophilic myositis and those that were unaffected were collected at an abattoir in Colorado and studied to determine the involvement of Sarcocystis spp. All affected carcasses contained similar granulomatous lesions with adjacent infiltrations of leukocytes. Intact or fragments of sarcocysts were found within 32 of 363 granulomas, and whole sarcocysts were present in nearby unaffected muscle cells. Light and electron microscopic examinations revealed that sarcocysts, affected or unaffected by cellular response in condemned carcasses, as well as those found in unaffected carcasses, were consistent with those of S. cruzi. Transmission experiments confirmed that S. cruzi were present in all carcasses, and that dogs, but not cats, were the definitive hosts. The results of pepsin-HCl digestion assays showed that unaffected carcasses that were approved for human consumption generally contained more infective parasites than carcasses that were condemned for eosinophilic myositis. This study provides evidence to support the suggestion that dogs, rather than cats, and unaffected rather than eosinophilic myositis-affected carcasses, have greater potential for contributing to the perpetuation of eosinophilic myositis in the cattle industry. PMID- 1586894 TI - Culling practices of Ontario cow-calf producers. AB - This study describes the distribution of herd culling rates for 123 Ontario cow calf herds maintaining individual animal records. Associations between culling and factors at both the individual and herd level were examined. In addition, the relative importance of individual animal and herd level influences on culling were investigated. The following individual cow culling risk factors: nonpregnancy, age, weaning weight index, calf outcome, abortion, prolapsed vagina, prolapsed uterus, calving injury, lameness and mastitis or udder problems were significantly associated with culling (p less than 0.01). Two herd level factors were associated with increased culling rates: a higher than average proportion of heifers and a shorter than average calving season (p less than 0.01). The proportion of culling variation attributed to individual animal and herd level influences varied with model type. While simple models (one-way ANOVA) indicated that the herd variance component for culling was relatively minor, more complex models indicated larger herd-to-herd variability (mixed model ANOVA). Thus, it appeared that the probability of culling for a cow with a given set of risk factors depended to an important extent on manager decisions in the herd of origin. PMID- 1586893 TI - Patterns of stillbirth and dystocia in Ontario cow-calf herds. AB - The association between a number of individual animal and herd level factors and calving problems in beef cows and heifers were examined. Data were from the 1987 calving season for a subset of 123 herds which maintained individual-animal records, from a sample of 180 randomly selected Ontario cow-calf herds. The median herd dystocia rate was 5.8% and 24.4% of herds had no dystocias. The median herd stillbirth rate was 2.8%, and 33.3% of herds had no stillbirths. Dystocias and stillbirths were much more common in heifers than in cows. Separate statistical models of dystocia and stillbirth for cows and heifers were created. Dystocia in cows was associated with calf sex, previous calving assistance and large breed type and birth weight. Variations in 1987 cow herd dystocia rates were associated with calving season, location and density, and the herd dystocia rate in 1986. Dystocia in heifers was associated with large breed type and calf birth weight. Herd-level management practices associated with increased heifer dystocia rates included breeding heifers to calve earlier than cows and rearing heifers together with the cow herd. Stillbirths for both cows and heifers were associated with calving assistance, particularly hard assistance. Herd-level management and other factors were unassociated with stillbirths. PMID- 1586895 TI - Serum haptoglobin concentration as an indicator of weight gain in pigs. AB - Serum haptoglobin concentration was investigated as an indicator of weight gain in commercially-reared pigs. The serum haptoglobin concentrations and weights of 40 pigs were monitored on a weekly basis, from weaning to 13 weeks of age. All data were ranked based on the week 13 weights, and divided into high, middle and low weight gain groups. By the fourth week of the study, when the pigs were seven weeks old, serum haptoglobin concentrations could be used to differentiate pigs that would have a high weight gain at the end of the study from those which would have a low weight gain. PMID- 1586896 TI - Inheritance of myotonic discharges in American quarter horses and the relationship to hyperkalemic periodic paralysis. AB - Electromyography (EMG) was used to detect myotonic discharges in Quarter Horse breeding stock and to follow the results of mating horses with hyperkalemic periodic paralysis (HPP). The studies were performed on two brood mare farms. A total of six breeding stock showed myotonic discharges and 15 were nonmyotonic. Myotonic discharges were seen in five of six horses belonging to the blood line previously implicated as being predisposed to HPP. Two of these horses had shown clinical signs of HPP. Only one of 15 breeding horses unrelated to the HPP predisposed blood line showed myotonic discharges. When both parents were non myotonic on EMG than the F1 generation (n = 6) were also nonmyotonic. When a stallion with HPP and myotonic discharges was mated to eight nonmyotonic mares over a six year period half the animals of the F1 generation (n = 25) showed myotonic discharges. When both parents showed myotonic discharges four F1 offspring were myotonic and two were nonmyotonic on EMG testing. There was no evidence of sex linkage. The results are consistent with an autosomal dominant mode of inheritance. Hyperkalemic periodic paralysis and myotonic discharges on EMG may be different manifestations of the same underlying defect. PMID- 1586897 TI - Preovulatory changes in follicular prostaglandins and their role in ovulation in cattle. AB - Indomethacin (INDO, n = 5) or vehicle (CONTROL, n = 4) was injected into superovulated heifers at 48 and 60 h following a luteolytic cloprostenol injection (0 h). One heifer from each group was ovariectomized (OVX) at 48, 56, 64 and 72 h. The fifth heifer of the INDO group was OVX at 80 h. Blood samples were collected at 0 h, every 2 h between 37 and 47 h, and at the time of each OVX to monitor plasma progesterone (P4) and luteinizing hormone (LH) concentrations. Following each OVX, the number and size of follicles were recorded and the incidence of ovulation determined. Follicular fluid (FF) was aspirated from follicles greater than or equal to 8 mm to determine the concentration of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha). The highest PG concentrations were measured in both groups at 24-25 h following the preovulatory LH surge and the PGF2 alpha concentration at this time was significantly greater (p less than 0.01) in the CONTROL group compared to the INDO group. By 35-36 h after the LH surge, 75% (25/34) of the CONTROL follicles had ovulated, whereas there were no ovulations (0/50) on either ovary of the INDO treated heifer. These preliminary results suggest that the preovulatory rise of PGs in FF, particularly PGF2 alpha, is essential for ovulation and that suppression of this rise with indomethacin will inhibit ovulation in heifers. PMID- 1586898 TI - Effects of mycobactin J and lactoferrin supplementation of drinking water on the in vivo multiplication of Mycobacterium paratuberculosis in gnotobiotic mice. AB - In this study the effect of supplementation of drinking water with mycobactin J or lactoferrin on the multiplication of Mycobacterium paratuberculosis in gnotobiotic mice was investigated. The results indicated that neither mycobactin J nor lactoferrin, at the doses used, appeared to have any effect on fecal shedding or tissue burdens of M. paratuberculosis. PMID- 1586899 TI - Basic pharmacology and pharmacokinetics. AB - The processes of absorption, distribution, metabolism, and elimination are involved in the determination of blood drug concentrations from a certain dosage regimen. Various physiologic factors ranging from gastric pH to hepatic blood flow can affect the pharmacokinetic parameters that help to describe these processes. The result of altered physiology may be a change in drug concentrations that may cause toxic effects or no desired effect. Therefore, the clinician must have a knowledge of basic pharmacokinetics and pharmacodynamics to be able to predict the behavior of drugs in a body and ensure that the drugs are used in a safe and effective way. PMID- 1586900 TI - Pharmacology. PMID- 1586901 TI - Drug interactions. AB - Drug-drug interactions are most likely to occur in patients receiving multiple medications and with drugs that have a narrow therapeutic window. The outcome may be harmful or beneficial, but the relative incidence of clinically important adverse drug interactions remains unknown. Many interactions may be minimized or avoided; the prescriber must be aware of this potential in order to take the necessary precautions. PMID- 1586902 TI - Hypoglycemic drugs. AB - There are an estimated 14 million individuals in the United States with diabetes mellitus. These individuals suffer a very high incidence of podiatric complications. This article focuses on the pharmacologic agents used in the management of hyperglycemia in the patient with diabetes mellitus, including insulin and sulfonylureas. PMID- 1586903 TI - Drug therapy of diabetic neuropathy. AB - Neuropathy is the most common and perhaps the most devastating complication associated with diabetes. Although many theories regarding the pathogenesis of diabetic neuropathies have been proposed, the most popular theory focuses on the accumulation of sorbitol in the nerve cell through the "polyol pathway." Treatment for diabetic neuropathy remains inadequate. Newer agents such as the aldose reductase inhibitors show some promise in halting and perhaps reversing the pathogenesis of this complication; however, these agents remain investigational. Currently, the most reasonable approach involves the use of agents to control pain and other symptoms associated with this progressive disease. PMID- 1586905 TI - Topical steroids. AB - Topical steroids are among the most frequently prescribed medications in the treatment of skin disease. Hundreds of preparations are currently available in a variety of vehicles and potencies. This article details the mechanism of action, determinants of clinical effectiveness, vehicle and potency selection, special considerations, and side effects of topical steroids. PMID- 1586904 TI - Antifungals: oral and topical. AB - This article discusses the mechanism of action, pharmacokinetics, and clinical efficacy of allylamine and triazole antifungal agents, griseofulvin, imidazoles, and clotrimazole. PMID- 1586906 TI - Nonsteroidal anti-inflammatory drugs. AB - Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most widely used medications today. Although their exact mechanism of action is unclear, inhibition of prostaglandin synthesis contributes significantly to their analgesic, anti-inflammatory, antipyretic, and antiplatelet effects. In recent years, additional mechanisms of action have been proposed for NSAIDs, and these may explain the variability commonly noted in patient response and tolerability to individual NSAIDs. NSAID therapy is not without risk, and serious adverse effects involving the gastrointestinal tract, kidneys, blood, and liver have been reported. PMID- 1586908 TI - Postoperative narcotic and nonnarcotic analgesics. AB - Narcotic analgesics may be used safely in most patients. Common adverse effects may be managed successfully with naloxone. PCA is a newer approach to the management of postoperative pain. The authors' survey results indicate that most podiatric physicians would benefit from the understanding of the considerations in the patient subgroups with renal or hepatic dysfunction that required postoperative pain control. PMID- 1586907 TI - Preoperative and therapeutic local anesthetics and steroids. AB - In a recent survey that the author conducted among podiatrists, the typical therapeutic injection for inflammatory lesions consisted of 2.25 or 2.5 mL of 1% lidocaine or plain bupivicaine (or, rarely, with epinephrine 1:200,000), 0.5 mL of hexadrol, and 0.25 mL of an insoluble cortisone such as triamcinolone acetonide (Kenalog). It is clear that variation exists and that each doctor has his or her own "cocktail" for therapeusis. The author finds that 1% lidocaine with epinephrine 1:200,000 therapeutic injections alone have a profound clinical effect when used in concert with biomechanic control. These injections are given as a series once a week and then the interphase is stretched out as needed. Because no steroids are used, there is no limit to the number of injections, and so, for chronic entities such as metatarsophalangeal (MTP) joint osteoarthritis, the author has been giving certain patients 6 to 10 therapeutic injections a year for 15 to 18 years, while controlling pain. Because all "cocktails" usually contain some amount of local anesthetic, maybe the podiatric community is using added medications such as steroids unnecessarily. Steroids mask poor diagnostic and technical skills and also infections. Clinicians also should spend time controlling the pedal sympathetics through "chemical sympathectomy." This posterior tibial nerve and artery therapeutic block was developed by Dr. Marvin Steinberg in the 1940s. Treatments are given in 1-week intervals with the first treatment giving 3 to 5 days' relief, the second 5 to 7 days, the third 7 to 10 days, and then 2- and 4-week intervals. Eventually, a comfortable interphase is selected, if necessary. In order for the blocks to work in summation, a vasoconstrictor such as epinephrine is mandatory. Lidocaine is the active ingredient of chemical sympathectomy; it blocks the artery and nerve, including the posterior tibial sympathetics. The posterior tibial sympathetics control 85% of the sympathetics to the foot, including all four muscle layers and the vital structures of the sole of the foot. Epinephrine works at the vasovasorum, nervonervorum, vasonervorum, and nervovasorum to maintain the active medication longer and make the block more effective. This chemical sympathectomy works even better than a lumbar paravertebral sympathectomy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1586909 TI - Clindamycin, erythromycin, and the newer macrolides. AB - Clindamycin continues to be an important agent for the management of infections due to gram-positive cocci and anaerobes. Such pathogens are frequently important in skin, soft tissue, and deep infections of the foot. Erythromycin has an impressive safety record and has retained its activity against many organisms, including several that play a role in infections of the foot. Clindamycin and erythromycin are frequently used as alternatives to the penicillins and cephalosporins. Newer macrolides, in comparison to erythromycin, have similar antimicrobial spectra of activity, improved pharmacokinetic parameters, and better tissue penetration. As new microorganisms emerge as clinical problems, newer macrolides may play a therapeutic role. PMID- 1586910 TI - Vancomycin, metronidazole, and tetracyclines. AB - Over the last 30 years, the impurities in the vancomycin product have been reduced, perhaps resulting in a lower rate of adverse reactions. Vancomycin is bactericidal against most susceptible organisms, but is bacteriostatic against the enterococcus. Vancomycin is the drug of choice for methicillin-resistant Staphylococcus aureus. Vancomycin attains good tissue and bone penetration and must be administered intravenously for systemic infections. It is eliminated renally with a half-life of about 6 hours; this half-life is prolonged with advanced age and reduced renal function. Significant adverse reactions can be minimized with careful attention to administration technique. Metronidazole has excellent tissue penetration; its antibacterial site of action is within anaerobic bacterial cells. Metronidazole is cleared by hepatic metabolism with a half-life of about 7 to 8 hours. The half-life is unchanged with renal dysfunction but is prolonged in patients with hepatic function impairment. Although adverse effects are relatively minor, there is an important interaction with warfarin. For podiatric infections, metronidazole can be used in skin- and soft-tissue infections; anaerobes in bone and joint infections are rare. Topical metronidazole has been used successfully in the treatment of decubitus ulcers, and this needs further evaluation. The most commonly used tetracyclines are tetracycline, doxycycline, and minocycline. The tetracyclines are broad spectrum antimicrobial agents, but their usefulness is limited by resistant strains. Tetracycline's absorption is significantly impaired by food, and it is cleared renally and fecally. Doxycycline has the highest protein binding and the longest half-life; it is cleared both renally and fecally without hepatic metabolism. Minocycline has the best absorption and tissue penetration; the unchanged drug is cleared renally and fecally, and it also undergoes hepatic metabolism. All tetracyclines have important adverse reactions with respect to teeth and bones, and they are contraindicated during pregnancy and for children under age eight. PMID- 1586911 TI - Aminoglycosides, imipenem, and aztreonam. AB - The aminoglycosides continue to be the cornerstone of antibiotic therapy for serious infections caused by gram-negative aerobic pathogens, even with the recent introduction of potent beta-lactams and the fluoroquinolones. Two of these newer agents are imipenem and aztreonam. Imipenem is the most expensive commercially available antibiotic, but it has the broadest range of activity, including most gram-negative and gram-positive, aerobic and anaerobic bacteria. Aztreonam, the first monobactam antibiotic to be released, has excellent activity against aerobic, gram-negative bacteria. It is not, however, simply a nonnephrotoxic replacement for aminoglycoside therapy. This article reviews the basic pharmacology and clinical utility of the aminoglycosides, imipenem, and aztreonam. PMID- 1586912 TI - Antianxiety/sedative drugs. The benzodiazepines. AB - Oral presurgical medication with benzodiazepines carries several distinct advantages; it often reduces the patient's anxiety and allows for a "smoother" surgical procedure, provides analgesia, facilitates venipuncture, aids in the patient's tolerance of an ankle tourniquet, limits postoperative nausea and vomiting, and provides varying degrees of retrograde amnesia. Many podiatric surgeons prefer using oral anxiolytics/sedatives along with local anesthesia for their surgical patients because they are simple to use with in-office surgery. Patients may prefer this method because it allows them a sense of control and eliminates the fear of being "put to sleep." This method, however, is not without its potential drawbacks, as noted. The surgeon must be keenly aware of all the patient's medical problems and potential allergies, and how they may impact on the use of these agents. He or she also must be prepared to act in an emergency should an adverse reaction occur. The recovery time from local anesthesia with oral sedation can often be longer than from general anesthesia, and discharge may be delayed. The patient may have an unsteady gait for the period prior to complete drug elimination and may require assistance. If an oral agent is chosen, it must be administered early enough to provide the desired effect at the desired time. The clinician must be aware of the time to onset and the duration of action of the drug chosen. Dosage adjustments must be considered in the elderly, individuals with medical disorders, and patients taking multiple medications. If IV premedication is selected, the clinician must be even more aware of its potential effects and well trained in emergency procedures. IV administration allows the patient to present to the surgical suite without being sedated. The medication should be given shortly after venipuncture; the patient then becomes relaxed and ready for the local anesthesia. Intravenous sedation can be maintained throughout the procedure by carefully titrating small incremental doses; however, this requires close observation and monitoring of vital signs. This route often results in a faster drug elimination, patient recovery, and discharge. It has been said that the best preoperative anxiolytic is a complete, thorough, and reassuring preoperative explanation of the events that are to follow.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1586913 TI - Cardiomyopathies in the elderly. AB - Cardiomyopathies are an important cause of congestive heart failure in the elderly, and the magnitude of the problem is compounded by changing population demographics and the frequency of congestive heart failure in the elderly. Although the data are far from complete, differences in the clinical presentations and natural history of the cardiomyopathies in older and younger patients are becoming more clearly appreciated. Dilated cardiomyopathy (DCM) is clearly more common than previously appreciated, and elderly patients have a worse prognosis than their younger counterparts with this disease. The medical management of DCM is often more difficult in the elderly, and the problem is compounded by the relatively infrequent use of cardiac transplantation as a therapeutic option. Hypertrophic cardiomyopathy is also more common than previously appreciated, and changes in left ventricular structure often create difficulties in differentiating pathologic states from physiologic. Fortunately, the prognosis for HOCM is more favorable in the elderly than in younger patients and may be partly accounted for by the different structure of the left ventricle. If needed, surgery is an option for elderly patients with medically refractory HOCM, but particular attention must be paid to the presence and severity of associated cardiovascular disease. Restrictive cardiomyopathy with diastolic dysfunction is increasingly recognized as a cause of congestive heart failure. The differentiation from systolic dysfunction is crucial, because the treatments are so markedly different. Age-related changes in diastolic function are becoming more apparent and better characterized, but standardization of age-related "normal" values is still not available. The diagnosis of restrictive heart disease should stimulate a search for an underlying cause, inasmuch as restrictive cardiomyopathy remains a diagnosis of exclusion. Advances in noninvasive imaging have led to a resurgence of interest and have enhanced our knowledge of the cardiomyopathies. Further investigation should proceed in conjunction with studies aimed at defining the characteristics and variables of "normal" aging. For the present, the enigmatic, poorly identified "cardiomyopathies" remain a problem for both young and old. PMID- 1586914 TI - Congestive heart failure in the elderly. AB - Congestive heart failure is in large part a disease of patients with advancing age. As our population ages, the incidence and prevalence of this disorder will continue to rise. The etiology of CHF in the elderly is multifactorial and one must take into account normal changes associated with aging, the heterogeneity of the elderly population, and possible noncardiac as well as cardiac disorders. Therapy must be aimed at the primary pathophysiologic process affecting the heart. Despite a number of therapeutic advances with medical therapy, CHF usually signals a generally irreversible process with a high mortality, especially in those patients with advanced disease. Therefore preventive measures should assume a paramount role in this disorder. Modification of risk factors such as diabetes, smoking, obesity, sedentary life style, and hypercholesterolemia should be aggressively stressed and pursued in patients of all ages. These preventive measures may have a substantial impact on the incidence of CHF in the elderly. PMID- 1586915 TI - Arrhythmias in the elderly. AB - The elderly patient is susceptible to a variety of cardiac rhythm disturbances that may or may not cause symptoms. It is incumbent on the physician who cares for geriatric patients to have a familiarity with the diagnostic criteria for each of these arrhythmias and with the drugs and devices that are used to treat them. This includes the potential adverse effects of therapy and methods to counter them. Even more important is a sense of when to intervene, which is based in part on a knowledge of "normal variation" in the aged. PMID- 1586916 TI - Cardiovascular drugs in the elderly. PMID- 1586917 TI - Intervention therapy for coronary artery disease in the elderly. AB - The central aim of this review was to examine the application of intervention therapy for CAD in the elderly population. The data reviewed indicates that it is no longer appropriate to use age 70 or 75 as the upper limit of eligibility for thrombolytic intervention in patients with acute myocardial infarction. Elderly who are physiologically active without contraindications to thrombolytic therapy should be considered eligible. Additional controlled trials specifically targeted at the elderly population are needed to better define the precise dosing regimen and the magnitude and extent of bleeding complications in this group. Nevertheless, it appears appropriate to recommend thrombolytic intervention for most eligible elderly patients presenting with acute myocardial infarction. This recommendation is based on the fact that the higher mortality in the elderly results in more lives saved per patient treated than for younger patients. It is important to reemphasize that this recommendation is for treating elderly patients with acute infarction as suggested by ST-segment elevation and/or Q waves, without contraindications to thrombolytic therapy. Those with non-Q-wave infarctions, hypertension, recent stroke, history of bleeding, or other contraindications are not candidates. Regarding intervention therapy in other elderly patients with acute and chronic manifestations of coronary disease, results also appear very encouraging. Elderly patients appearing to tolerate PTCA include those with all forms of angina from chronic stable angina to unstable angina. Although only observational data are on hand at present, our review suggests these elderly patients tolerate PTCA well and indeed may benefit. The elderly patients who have co-morbid factors that adversely influence the application of CABG for revascularization may be the best candidates for PTCA. At present, the challenge for the physician is to carefully assess each elderly patient on an individual basis for intervention therapy. This evaluation should be aimed at identifying factors that may permit application of intervention treatment to the elderly patients who are most likely to receive the greatest benefit. PMID- 1586918 TI - Cardiac surgery in the elderly patient. AB - The decision to proceed with cardiac valve surgery in patients older than 70 years must be made with careful deliberation. Clearly, the risks of surgery are increased, but the potential benefits in rehabilitating the individual back to a productive and full life are real. An aggressive surgical approach should be taken in patients with aortic stenosis. More caution should be used in advocating mitral valve or double-valve replacement in the elderly, especially when other factors place these individuals in a high-risk category. Both patients and their families should be fully aware of the potential risks and benefits in weighing their decision to proceed with surgical therapy. PMID- 1586919 TI - Rehabilitation and life-style modification in the elderly. AB - The projected growth of the elderly population in the United States in the coming years underlines the importance of assuring that the quality of life for older persons is maintained. Because CHD is prevalent in this population, measures for preventing disease as well as for optimizing the abilities of those with disease will assume greater significance. Exercise training is a key component in achieving and maintaining optimal capacities in the elderly cardiac and noncardiac populations. These groups can safely undergo exercise training with proper screening and program design. Modifications in the components of the exercise prescription (i.e., frequency, intensity, duration, and activity mode) must be individualized according to the abilities, needs, and goals of each person. Risk factors for CHD still prevail in the elderly, although the predictive value of some risk factors may change with age. For this reason, efforts to control risk factors in older individuals should still be effective in reducing risk from CHD. Dietary modification, weight control, blood pressure control, smoking cessation, and endurance exercise training are several of the interventions used in concert to control risk for CHD. PMID- 1586920 TI - The relationship between socioeconomic status and coronary heart disease in older patients: implications for health care. PMID- 1586921 TI - Ethical considerations and quality of life. PMID- 1586923 TI - Geriatric cardiology. PMID- 1586922 TI - Cardiovascular consequences of the aging process. AB - The normal aging process is associated with a variety of cardiovascular changes. Recognition of these alterations in cardiovascular structure and function that occur in the aging population is essential for assessment of cardiac disease in older patients. For example, a number of studies show that aging is associated with increasing left ventricular wall thickness and mass. However, these changes are gradual and relatively mild, and absolute wall thickness measurements in individual elderly subjects rarely exceed generally accepted normal values. Parameters of left ventricular systolic function (either under basal conditions or with exercise) change little with aging. In contrast, apparent alterations in left ventricular diastolic filling patterns often accompany advancing age. Investigations in normal elderly subjects have shown that the early filling phase is prolonged, and the rate and volume (as well as flow-velocity) of rapid filling are decreased. These alterations are associated with a compensatory increase in late diastolic filling with atrial systole. The aging changes in left ventricular filling identified by noninvasive tests (such as Doppler echocardiography or radionuclide angiography) may mimic in appearance those observed in a number of cardiovascular diseases, making interpretation of their clinical significance difficult in an elderly population. PMID- 1586924 TI - Demographics of aging. PMID- 1586925 TI - Changes with aging as reflected in noninvasive cardiac studies. PMID- 1586926 TI - Hypertension in the elderly. PMID- 1586927 TI - Clinical features of coronary heart disease in the elderly. AB - Care of the elderly patient with CHD requires an understanding of the prevalence of disease and its variability of presentation. Sound application of the diagnostic and therapeutic maneuvers developed for younger patients remains the predominant basis for the clinical approach to older individuals with heart disease. As more research is directed toward age-related issues in cardiac disease, the approach may be refined with more specific guidelines than are currently available. PMID- 1586928 TI - Evaluation of valvular heart disease in patients older than age 65. PMID- 1586929 TI - Pericardial disease in the elderly. PMID- 1586930 TI - [The heart beat--the rhythm of health. The origin of the World Health Organization]. PMID- 1586931 TI - [Prevention of thromboembolic complications in surgery]. AB - It is known that during the postoperative period about 25-50% operated patients develop postoperative venous thrombosis. The mechanism of development of postoperative thrombosis is promoted in surgical patients by the so-called "wound healing process" with an enhanced synthesis of fibrinogen, inhibitors of fibrinolysis and other proteins of the acute phase for release of various cytokins (IL-1, IL-6, TNF, TGF and others). The development of thrombosis is promoted also by other risk factors: advanced age, extensive surgical trauma, infection, immobility, obesity etc. Preventive administration of so-called small doses a of heparin or rather so-called low molecular heparin (LMWH) substantially reduces the risk. The authors submit also a list of drug with an antithrombotic action and rheologics. PMID- 1586932 TI - [The ACE inhibitor, enalapril, in portal hypertension. A prospective placebo controlled study]. AB - The haemodynamic action of long-term (3 months) therapy with enalapril, a potent inhibitor of angiotensin convertase was investigated in 12 patients selected at random, all suffering from portal hypertension and a previous episode of haemorrhage from oesophageal varices. In all these patients after one-week intervals sclerotization of oesophageal varices was made. As controls served a group of 13 patients treated only by sclerotherapy and placebo. In the enalapril treated group after three months the pressure in the wedged hepatic vein (25 +/- 4.8 vs. 21.3 4.8 mm Hg) and the pressure gradient wedged free hepatic vein (17.0 +/- 6.0 vs. 12.6 +/- 3.4 mm Hg) were significantly lower than the initial values (p less than less than 0.01) in the enalapril treated group. A very marked decline (greater than 3 mm Hg) of this pressure was recorded in 50% of the patients. In the group treated by sclerotherapy and placebo the pressure gradient did not decline. During treatment no changes in the systemic haemodynamics and liver tests occurred. None of the patients died during the investigation and the subsequent 6-month period. The authors provided evidence that enalapril reduces the portal pressure in patients with hypertension, although not in all, and can be successfully used for the treatment of patients with oesophageal varices in combination with sclerotherapy. PMID- 1586933 TI - [IgA nephropathy. Morphology, clinical picture and significance of mesangial fibrin deposits]. AB - IgA nephropathy was diagnosed in 114 biopsies from 107 patients comprising 78% men. Light microscopy revealed most frequently mild proliferative glomerulonephritis with frequent though rudimentary extracapillary proliferation (in one quarter of the biopsies). Allergic manifestations in the case-history were recorded in 14% of the patients. Almost in one third of the patients the disease started by macroscopic erythrocyturia. A typical finding in urine was predominating erythrocyturia (tens of millions in Addis sediment) over proteinuria (usually less than 1.5 g/24 h). Cumulative "renal survival rate" ten year after biopsy was 84%, the cumulative ratio of remissions was 30%. Mesangial fibrinoid deposits were found in half the patients with a severe course of the condition. PMID- 1586934 TI - [Significance of the complement fixation reaction in the diagnosis of the acute phase of lymphatic toxoplasmosis]. AB - In a group of 300 sera of subjects with clinically suspect nodular toxoplasmosis the authors tested by the IgM ELISA reaction in the reverse order the importance of the complement-fixation reaction for assessment of the acute stage of the infection. In view of the revealed prolonged detection of IgM antibodies the authors used quantitative evaluation of the reaction; they consider based on a probability pattern of antibody response coefficients of 10 and above important for differentiation of a recent infection. For the suggested method of evaluation it was confirmed that low CFR titres (1:8, 1:16, 1:32) imply usually (89.5%) latent infection, titres of 1:64 chronic (42.8%) and latent infection (57.2%); in no instance onset of the disease was involved. From the titre of 1:128 onwards there is a proportional increase of the probable detection of acute infections (titre 1:1024 as much as 72.7%. However, even high titres are not unequivocal evidence of recent infection. In view of the equivocal interpretation of results of the CFR the authors recommend for assessment of the acute stage of the nodular form of toxoplasmosis examination of the suspect subject by the CFR and in case of a medium or high level assessment of IgM by the ELISA method focused on the level and dynamics of the coefficient. PMID- 1586935 TI - [Combined therapy of hyperlipoproteinemia. Colestipol and gemfibrozil in the treatment of heterozygous familial hypercholesterolemia]. AB - Combined concurrent treatment with two or more hypolipidaemic agents is a modern trend in the pharmacotherapy of hyperlipoproteinaemias. Aggressive treatment of hyperlipoproteinaemias can lead not only to the arrest of progression but also to regression of the atherosclerotic process. The authors submit experience assembled with the treatment of 14 heterozygotes with familial hypercholesterolaemia by a combination of colestipol (Colestid Upjohn, Belgium) with gemfibrosil (Loped Parke-Davis, USA), 15 g and 1200 mg resp. per day. One month of administration of this combination of hypolipidaemic agents led to a drop of total cholesterol by 21% and of LDL-cholesterol by 30%. At the same time the authors recorded a marked and statistically significant increase of HDL cholesterol by 23%. Favourable changes were observed also as regards apolipoprotein concentrations. The apolipoprotein A-1 level increased by 32%, while the level of the atherogenic apolipoprotein B declined by 30%. The triglyceride level declined also. It did not prove possible even by combined treatment to reduce the level of apolipoprotein(a). Combined treatment with colestipol and gemfibrosil was well tolerated by the patients and in none of the patients treatment had to be discontinued because of undesirable side-effects. PMID- 1586936 TI - [Gustav Kabrhel and the Prague Hygiene School. On the 100 anniversary of the appointment of the first professor of hygiene at the Czech Medical School in Prague]. PMID- 1586937 TI - Effect of lysophospholipids, arachidonic acid and other fatty acids on regulation of Ca2+ transport in permeabilized pancreatic islets. AB - The immediate reaction products of PLA2-mediated hydrolysis of phospholipids were tested for their ability to induce Ca2+ mobilization from internal stores in permeabilized ob/ob mouse pancreatic islets. Lysophospholipids and unsaturated fatty acids increased the free Ca2+ concentration in the incubation medium of permeabilized ob/ob mouse pancreatic islets. The potency of the lysophospholipids decreased in the following order: lysophosphatidylcholine = lysophosphatidylglycerol much greater than lysophosphatidylinositol greater than lysophosphatidylserine much greater than lysophosphatidylethanolamine. Arachidonic acid and palmitoleic acid had a potency comparable to lysophosphatidylinositol, while palmitic acid was ineffective. The Ca(2+) mobilizing effect of inositol-1,4,5-trisphosphate (IP3) in permeabilized islet cells was additive to the lysophospholipid effect, indicating different sites of action. Both Ca(2+)-mobilizing effects were counteracted by the polyamine spermine, while the presence of Mg2+ shifted the Ca2+ concentrations to higher levels. Since not only an activation of a phospholipase C but also an activation of a phospholipase A2 with subsequent generation of lysophospholipids and free fatty acids is reported to occur in glucose-induced insulin secretion, the interaction of the phospholipase C reaction product IP3 with a lysophospholipid or an unsaturated fatty acid may affect the extent and duration of the rise in the free cytoplasmic Ca2+ concentration responsible for initiation of insulin secretion. PMID- 1586938 TI - Interactions of calcium with yeast mitochondria. AB - The interactions of Ca2+ with mitochondria from Saccharomyces cerevisiae were explored. Mitochondria were loaded with the metallochromic dye Fluo-3 to measure the concentration of free calcium in the matrix. Addition of EGTA or Ca2+ led to fluctuations in mitochondrial free calcium between 120 and 400 nM. Ca2+ variations were slower at 4 degrees C than at 25 degrees C or in the presence of phosphate instead of acetate. The net uptake of 45Ca2+ was higher with phosphate than with acetate. The optimum pH for Ca2+ uptake was 6.8. Ruthenium red did not affect the uptake of Ca2+. Addition of antimycin-A or uncouplers led to a small and transient release of Ca2+. Addition of EGTA or the monovalent cations Na+ or K+ resulted in higher release of Ca2+. Site I but not site II dependent O2 consumption was partially inhibited by EGTA. The effect of Ca2+ on NADH oxidation is similar to results reported with enzymes from mammalian sources which use NADH, such as the pyruvate, isocitrate and oxoglutarate dehydrogenases. PMID- 1586939 TI - Glucose sensing of individual pancreatic beta-cells involves transitions between steady-state and oscillatory cytoplasmic Ca2+. AB - Glucose stimulation of individual pancreatic beta-cells is associated with a rise of the cytoplasmic Ca2+ concentration ([Ca2+]i) manifested either as large amplitude oscillations (0.2-0.5/min) or as a sustained increase. Determinants for the transitions between the basal and the two stimulated states have now been studied using dual-wavelength fluorometric measurements on individual ob/ob mouse beta-cells loaded with the Ca2+ indicator Fura-2. The transition from the basal state to large amplitude oscillations was induced by raising the glucose concentration to 7 mM or above. The frequencies and shapes of the [Ca2+]i cycles remained largely unaffected when raising glucose as high as 40 mM. However, in some cells the oscillatory pattern was transformed into a sustained increase of [Ca2+]i at high glucose concentrations. Although the peak values for the oscillations exceeded the steady-state increase, the time average [Ca2+]i was higher during the latter phase. Both types of glucose-induced transitions were facilitated by the presence of 1-100 nM glucagon. Protein kinase C activation by 10 nM of the phorbol ester TPA resulted in a transformation of the glucose induced oscillations into a sustained increase of [Ca2+]i but the levels reached were considerably lower than obtained with glucose alone. It is concluded that the glucose sensing of the individual beta-cell is based on sudden transitions between steady-state and oscillating cytoplasmic Ca2+. It is these transitions rather than alterations of the oscillatory characteristics which determine the average [Ca2+]i regulating insulin release. PMID- 1586940 TI - Intracellular calcium 'signatures' evoked by different agonists in isolated bovine aortic endothelial cells. AB - Agonist induced increases in intracellular free calcium, [Ca2+]i, were measured in single Fura-2 loaded bovine aortic endothelial (BAE) cells by dual wavelength microspectrofluorimetry. Low doses of ATP (less than 10 microM) induced complex changes in [Ca2+]i. These changes usually consisted of a large initial transient peak with subsequent fluctuations superimposed upon a maintained rise in [Ca2+]i. Higher doses of ATP (greater than 50 microM) produced much simpler biphasic increases in [Ca2+]i in individual cells. Acetylcholine and bradykinin also elicited increases in [Ca2+]i in single cells in confluent monolayers of endothelial cells. However, only acetylcholine produced complex fluctuations. High doses of acetylcholine evoked simple rises in [Ca2+]i similar to those seen with high doses of ATP. In contrast, bradykinin evoked relatively simple rises in [Ca2+]i at all doses used. These results indicate that the mechanisms responsible for generating agonist induced increases in [Ca2+]i in BAE cells are not homogeneous. ATP and acetylcholine produced more complex Ca2+ changes or 'signatures' in single confluent bovine aortic endothelial cells than bradykinin. All three agonists appeared to release Ca2+ from intracellular stores as well as stimulating Ca2+ influx. The possible mechanisms underlying these phenomena are discussed. PMID- 1586941 TI - Fast axonal transport is modulated by altering trans-axolemmal calcium flux. AB - Factors involved in fast axonal transport (motor proteins, microtubules, organelles, etc.) have been identified but the molecular mechanism controlling transport is unknown. We used video enhanced microscopy to directly evaluate the effect of calcium on fast axonal transport (FAxT). FAxT alterations included rapid speed decreases (within minutes) in Ca2+ free buffer and rapid speed increases (within seconds) when axons were treated with parathyroid hormone, BAY K 8644, or K+ depolarization. The speed increases were blocked by dihydropyridine Ca2+ channel antagonists. Ryanodine (20 microM), known to block calcium release from subcellular stores, caused a decrease in the rate of retrograde FAxT. Calcium ionophore A23187 (at 1 and 20 micrograms/ml) caused increases in FAxT, an effect also noted only in retrograde moving organelle traffic. Hyper- or hypo tonic solutions produced no alterations making axoplasmic viscosity changes an unlikely explanation for the speed changes. Reproducible alteration of FAxT by manipulation of Ca2+ levels provides evidence that Ca2+ modulates fast axonal transport. Retrograde transport appears more sensitive to changes in Ca2+ and differential effects on antero- and retro-FAxT mechanisms suggest directional specificity for some of these signals which may be based upon the organelle size. Endogenous substances (e.g. PTH) that trigger axonal Ca2+ changes may rapidly modulate the rate of material delivery in axons. The results are discussed within the context of a Ca2+/calmodulin-dependent modification of the cytoskeletal matrix. PMID- 1586942 TI - Thapsigargin increases cytoplasmic free Ca2+ without influencing steroidogenesis in chicken granulosa cells. AB - The effects of thapsigargin on intracellular Ca2+ concentration ([Ca2+]i) and progesterone production were determined in granulosa cells from the two largest preovulatory follicles of laying hens. [Ca2+]i was measured in cells loaded with the Ca(2+)-responsive fluorescent dye Fura-2. Thapsigargin stimulated a 4.6 +/- 0.2-fold increase in [Ca2+]i from a resting level of 55 +/- 6 nM up to 233 +/- 23 nM (n = 8) in 100% of the cells tested (n = 86). However, two different response patterns were observed. Dependent on the cell populations, a maximally effective concentration of thapsigargin (100 nM) stimulated either a rapid (within 16 +/- 2 s) transient increase in [Ca2+]i or a slowly (99 +/- 20 s) developing and sustained increase in [Ca2+]i. Both [Ca2+]i responses were concentration (0.001-1 microM)-dependent with an EC50 around 40 nM. The transient [Ca2+]i response occurred in the absence of extracellular Ca2+ and was unaffected by pretreating the cells with the Ca2+ channel blockers methoxyverapamil (50 microM) or lanthanum (1 mM). The plateau phase of the sustained [Ca2+]i response returned to resting level in the absence of extracellular Ca2+, but remained elevated in the presence of methoxyverapamil (50 microM) or lanthanum (1 mM). Despite its ability to cause transient or prolonged increases in [Ca2+]i, thapsigargin (0.001-1 microM) did not affect basal or luteinizing hormone-stimulated progesterone production by chicken granulosa cells. PMID- 1586943 TI - Translocation of a specific premessenger ribonucleoprotein particle through the nuclear pore studied with electron microscope tomography. AB - A specific premessenger ribonucleoprotein (RNP) particle in the salivary glands of the dipteran Chironomus tentans was studied with electron microscope tomography during translocation from the cell nucleus to the cytoplasm. The RNP particle consists of a thin RNP fiber tightly folded into a ribbon, which is bent into a ring-like structure. Upon translocation through the pore, the particle is first orientated in a specific manner at the pore entrance, and subsequently the bent ribbon is gradually straightened and transported through the pore with the 5' end of the RNA in the lead. Concomitantly, the elementary RNP fiber constituting the ribbon is gradually unpacked and will appear more or less extended on the cytoplasmic side of the pore complex. The ordered nature of the process suggests a specific recognition of the RNP particle at the nuclear pore. PMID- 1586944 TI - Culmination in Dictyostelium is regulated by the cAMP-dependent protein kinase. AB - We placed a specific inhibitor of cyclic AMP-dependent protein kinase (PKA) under the control of a prestalk-specific promoter. Cells containing this construct form normally patterned slugs, but under environmental conditions that normally trigger immediate culmination, the slugs undergo prolonged migration. Slugs that eventually enter culmination do so normally but arrest as elongated, hairlike structures that contain neither stalk nor spore cells. Mutant cells do not migrate to the stalk entrance when codeveloped with wild-type cells and show greatly reduced inducibility by DIF, the stalk cell morphogen. These results suggest that the activity of PKA is necessary for the altered pattern of movement of prestalk cells at culmination and their differentiation into stalk cells. We propose a model whereby a protein repressor, under the control of PKA, inhibits precocious induction of stalk cell differentiation by DIF and so regulates the choice between slug migration and culmination. PMID- 1586945 TI - DNA cleavage in trans by the active site tyrosine during Flp recombination: switching protein partners before exchanging strands. AB - Each recombination event mediated by the Flp recombinase is the sum of four strand breakage and reunion reactions executed in two steps of two-strand exchanges. The reaction requires four Flp monomers. The key catalytic residue in Flp is Tyr-343. Arg-191, His-305, and Arg-308 appear to facilitate the cleavage and exchange steps of recombination. These four residues constitute the invariant tetrad of the Int family site-specific recombinases. Complementation tests between "step-arrest" mutants of Flp suggest that each Flp protomer harbors a "fractional active site." Hybrid "half site-recombinase" complexes reveal that efficient catalysis occurs when the Arg-His-Arg triad is present on one Flp monomer and the active site Tyr on a second monomer. Strand cleavage by an Flp monomer occurs virtually exclusively on the half site to which its partner protein is bound (cleavage in trans), and almost never on the half site to which it is bound (cleavage in cis). Trans-cleavage by Flp can provide a means for functionally exchanging Flp monomers between two DNA partners. Such a mechanism would be germane to recombination, since cleavage and rejoining in cis can only restore the parental substrate configuration and cannot yield recombinants. PMID- 1586946 TI - The A. tumefaciens transcriptional activator OccR causes a bend at a target promoter, which is partially relaxed by a plant tumor metabolite. AB - Octopine is released from crown gall tumors as a nutrient source and a signal molecule for the plant pathogen Agrobacterium tumefaciens. Some or all octopine inducible genes are regulated by a protein called OccR. Primer extension analysis showed that OccR protein represses the occR gene and both represses and activates the occQ operon, which is divergently transcribed from occR. These promoters initiate transcription 46 bp apart. This regulatory system was reconstituted in vitro using purified OccR protein and Escherichia coli RNA polymerase. OccR binds with high affinity to a single site overlapping these promoters. Octopine shortens the DNAase I footprint of OccR and increases the gel mobility of OccR DNA complexes by relaxing an OccR-incited DNA bend. PMID- 1586947 TI - The TATA-binding protein is required for transcription by all three nuclear RNA polymerases in yeast cells. AB - Using temperature- and proteolytically sensitive derivatives to inactivate the function of the yeast TATA-binding protein (TBP) in vivo, we investigated the requirement of TBP for transcription by the three nuclear RNA polymerases in yeast cells. TBP is required for RNA polymerase II (pol II) transcription from promoters containing conventional TATA elements as well as functionally distinct promoters that lack TATA-like sequences. TBP is also required for transcription of the U6 snRNA and two different tRNA genes mediated by RNA pol III as well as transcription of ribosomal RNA mediated by RNA pol I. For all promoters tested, transcription decreases rapidly and specifically upon inactivation of TBP, strongly suggesting that TBP is directly involved in the transcription process. These observations suggest that TBP is required for transcription of all nuclearly encoded genes in yeast, although distinct molecular mechanisms are probably involved for the three RNA polymerase transcription machineries. PMID- 1586948 TI - Variants of the TATA-binding protein can distinguish subsets of RNA polymerase I, II, and III promoters. AB - Transcription extracts prepared from yeast that are deficient in the TATA-binding protein (TBP or TFIID) are also impaired in specific promoter recognition by all three nuclear RNA polymerases (pol I, II, and III). Specific initiation can be rescued by the addition of purified recombinant TBP, demonstrating that pol I, II, and III all require this factor. A mutation of TBP has been identified that will function with pol I but not with pol II or III. Conversely, another mutation, which inactivates TATA element binding in vitro, will function with pol I and III promoters but is inactive for a pol II promoter. Thus, it is possible to identify TBP variants that will only function on different subsets of all nuclear promoters. PMID- 1586949 TI - The mechanism of RU486 antagonism is dependent on the conformation of the carboxy terminal tail of the human progesterone receptor. AB - The human progesterone receptor form B (hPR-B) was expressed in Saccharomyces cerevisiae together with a specific reporter plasmid. To understand the mechanism underlying antagonist ligand activity, libraries of hormone binding domain (HBD) mutated hPR-B molecules were prepared. A mutant receptor was identified that had lost the ability to bind either progesterone or R5020; it could still bind RU486 and, surprisingly, fully activated transcription in the presence of this "antagonist" and other antiprogestins. When this receptor mutant was assayed in mammalian cells, RU486 again demonstrated agonistic activity. Sequence analysis indicated that the mutant phenotype was due to truncation of the carboxy (C) terminal 42 aa. We conclude that amino acids in the extreme C-terminal region are required for the receptor to bind progesterone, while antagonists bind to a site located more N-terminal of the HBD. Our results suggest that the extreme C terminal region of the receptor contains an inhibitory function that silences receptor transactivation in the absence of agonist and in the presence of antagonist. PMID- 1586950 TI - Ability of tolerized Th1 and Th2 clones to stimulate B cell activation and cell cycle progression. AB - Tolerant and nontolerant murine Th1 and Th2 clones, specific for human gamma globulin (HGG), were compared for their ability to promote cell cycle entry and progression by B cells in vitro. When stimulated with HGG, nontolerant Th1 and Th2 clones induced similar increases in B cell membrane MHC class II levels--a phenomenon associated with early B cell activation. Nontolerant Th1 and Th2 clones also induced B cell DNA synthesis, an event associated with subsequent G1 phase traversal, although Th2 cells were more efficient than Th1 cells in stimulating this activity. Exposure of Th clones to tolerogen in the form of HGG pulsed chemically fixed APC inhibited the ability of Th1 clones, but not Th2 clones to promote polyclonal B cell DNA synthesis in HGG-stimulated secondary cultures. However, Th1 clones exposed to tolerogen did not lose their ability to increase the expression of MHC class II molecules on B cells in these cultures. These results indicate that tolerance induction does not inhibit the ability of Th1 clones promote B cell cycle progression. In contrast, exposure of Th2 cells to tolerogen does not inhibit significantly the ability of these cells to stimulate B cell cycle entry or progression. PMID- 1586951 TI - The origin and fate of beta 2m-free MHC class I molecules induced on activated T cells. AB - We report here that the expression of major histocompatibility complex (MHC) class I heavy chains not associated with beta 2-microglobulin is induced on resting human T cells by a variety of stimuli. These beta 2m-free class I heavy chains are not transported as such from the endoplasmic reticulum but originate from surface beta 2m-associated MHC class I molecules. beta 2m-free class I heavy chains are spontaneously released from the surface of activated cells. Cross linking of beta 2m-free class I heavy chains with specific monoclonal antibodies results in the rapid down-regulation and internalization of these molecules. In contrast, beta 2m-associated MHC class I molecules display a different pattern of modulation. Previously, we reported that beta 2m-free class I heavy chains interact with CD8 molecules expressed on the same activated T cells. We propose that interactions between these molecules are involved in a mechanism regulating the function of activated T cells. PMID- 1586952 TI - Activation of extrathymic T cells in the liver and reciprocal inactivation of intrathymic T cells by bacterial stimulation. AB - We recently demonstrated that the liver might be a major site of extrathymic T cell differentiation, including both alpha beta and gamma delta T cells. This extrathymic pathway in the liver, which has a relatively minor role in normal young mice, is activated in mice under bacterial stimulation. In the present study, we investigated how the extrathymic and intrathymic T cell differentiations were mutually related in mice injected intravenously with 10(8) heat-killed Escherichia coli. Three days after stimulation, extrathymic T cells in the liver were observed to be prominently activated in terms of increases in the total number of cells yielded, spontaneous cell proliferation in in vitro culture, and intermediate alpha beta TCR cells. Intermediate alpha beta TCR cells were extrathymic T cells uniquely seen in the liver. However, at the same time intrathymic T cells were profoundly inactivated, showing decreases in the number of thymocytes (more than 90% atrophy), spontaneous cell proliferation, and dull TCR cells with double positive CD4+8+ phenotype. With time, these responses were reversed and normal states were regained. These results suggested that extrathymic and intrathymic T cells are always activated or inactivated in the opposite direction, and that the liver and the thymus are dynamic immune organs. It raises the possibility that the extrathymic T cell differentiation in the liver and the intrathymic T cell differentiation may be reciprocally regulated by certain factors. PMID- 1586953 TI - Candida albicans hyphal form enhances tumor necrosis factor mRNA levels and protein secretion in murine ANA-1 macrophages. AB - We have demonstrated that Candida albicans in its hyphal form (H-Candida) acts as a stimulating agent in the cloned macrophage population ANA-1. Both tumor necrosis factor (TNF) mRNA levels and secreted biological activity augment in ANA 1 macrophages exposed to H-Candida. Such effects are observed at an effector-to target cell ratio of 1:1 and occur after 1 and 3 hr of coincubation, respectively. The phenomenon is independent of the metabolic status of the fungus, since viable as well as heat-killed H-Candida are comparable in inducing TNF mRNA levels. The extent and kinetics of H-Candida-mediated effects are similar to those observed following exposure of ANA-1 macrophages to lipopolysaccharide (LPS). This implies that C. albicans in its hyphal form is a potent macrophage modulator; whether it acts through the same mechanism(s) as LPS remains to be elucidated. PMID- 1586954 TI - Exogenous interleukin-2 abrogates differences in the proliferative responses to T cell mitogens among inbred strains of mice. AB - The proliferative response of spleen cells from BALB/c mice to stimulation with a T cell mitogen, concanavalin A (Con A), was two or more times stronger than that of cells from C57BL/10SnSc (B10) mice. In contrast, the cells from B10 mice responded better to B cell mitogen bacterial lipopolysaccharide (LPS). The differences in the proliferative response to Con A stimulation were not associated with the function of macrophages nor did they depend on IL-1. Spleen cells from BALB/c and B10 mice synthesized comparable amounts of mRNA for IL-1 alpha, and the production of biologically active IL-1 was even higher in the B10 strain. Indomethacin, an inhibitor of prostaglandin synthesis, had no effect on the differences in reactivity between the cells from BALB/c and B10 mice. In addition, no differences in the synthesis of mRNA for the inducible 55-kDa interleukin-2 (IL-2) receptors were found between the spleen cells from BALB/c and B10 mice. However, Con A-stimulated spleen cells from B10 mice produced a significantly lower amount of biologically active IL-2 than similarly stimulated cells from BALB/c mice. In the presence of exogenous IL-2, these low responder spleen cells from the B10 mice responded by proliferation to Con A stimulation to the same extent as cells from the BALB/c mice. These results thus show that a low proliferative response to Con A stimulation in B10 mice was a consequence of a lower production of IL-2 and possibly abrogated the proliferative hyporeactivity produced by exogenous IL-2. We suggest that the differences in the ability to produce IL-2 could be a reason for the discrepancies observed in the immunological responsiveness between BALB/c and B10 mice. PMID- 1586955 TI - CD69 molecule in human neutrophils: its expression and role in signal-transducing mechanisms. AB - The CD69 glycoprotein is an early activation antigen of T and B lymphocytes and it is constitutively expressed on thymocytes and platelets. Here we report its presence on neutrophils and on bone marrow-derived myeloid precursors. Indeed, promyelocytic cells are CD69+ on the cell membrane, while in resting neutrophils this molecule is located inside the cell. However, intracellular CD69 molecules are rapidly mobilized to the cell surface upon activation by PMA or fMLP. This translocation is independent on a new protein synthesis, as it is not inhibited by cycloheximide; furthermore, CD69 molecules are likely stored in a trans-Golgi structure since their expression is not affected by brefeldin A, a drug that blocks molecular trafficking from ER to Golgi vesicles. Immunoprecipitation of CD69 molecules either from activated neutrophils or from bone marrow cells showed that this protein has the same molecular size (28-34 kDa) as observed in platelets, T and B lymphocytes, and thymocytes. This similarity is reflected also in the functional role played by this molecule: in neutrophils as well as in lymphocytes and platelets, CD69 stimulation induced Ca2+ influx through cellular membrane; furthermore, the perturbation of the CD69 antigen on PMA-activated neutrophils enhances the lysozyme release, suggesting a role of this molecule in the regulation of granule exocytosis, probably through a Ca(2+)-dependent mechanism. PMID- 1586956 TI - Evidence for clonal heterogeneity of the expression of six protein kinase C isoforms in murine B and T lymphocytes. AB - Protein kinase C (PKC), which plays a pivotal role in lymphocyte activation, represents a homologous family of at least nine proteins. Seven genes that encode PKC proteins have been identified. Since the regulatory properties and substrate specificities of the isoforms are not identical in vitro, it is possible that each isoform plays a unique role in cell activation. Toward an understanding of the role of PKC isoforms in lymphocyte activation we have studied the expression of mRNA encoding six of the isoforms (alpha, beta, gamma, delta, epsilon, and zeta) in T cell clones and B cell lines. PKC isoform phenotyping was done by MAPPing using isoform-specific primers and slot-blot analyses of mRNA were performed using specific probes. T cell clones and B cell lines were determined to express levels of the delta, epsilon, and zeta isoforms of PKC that were detectable by MAPPing. Plasmacytomas did not express PKC-beta message detectable by MAPPing. Slot blot analyses and Western blot analyses with peptide-specific antibody confirmed that B cell plasmacytomas did not express PKC-beta mRNA or protein. T cell clones and B cell lines were similar in that none expressed PKC gamma. In cells that expressed PKC isoforms that were detectable by the MAPPing protocol, there was heterogeneity in the relative abundance of isoform mRNA (PKC delta and -beta) and protein (PKC-beta and -epsilon). Such diversity of isoform expression could be responsible for the differential responsiveness of lymphocyte clones to activating stimuli. PMID- 1586957 TI - Experimental allergic encephalomyelitis and multiple sclerosis: immunoregulatory mechanisms and T cell repertoires. PMID- 1586958 TI - Mechanism of target cell recognition by CD3- LGL. I. Development of a monoclonal antibody to a K562-associated target cell antigen. AB - In an attempt to identify the target recognition molecule(s) involved in the interaction between CD3- large granular lymphocyte (LGL) and a tumor cell target, monoclonal antibodies (mAb) to NK-susceptible K562 tumor cell membrane glycoproteins were developed. After screening by ELISA for reactivity to K562 membrane glycoproteins, two monoclonal antibodies were identified (mAb 35 and mAb 36). One of the monoclonal antibodies (mAb 36) was found to inhibit conjugation between LGL and K562 target cells and also to inhibit lysis of K562 by LGL. Upon further testing, mAb 36 also inhibited the binding between LGL and other NK susceptible target cells, e.g., Daudi and Molt 4. In contrast, mAb 35, even though binding to K562, did not inhibit the binding of LGL to tumor targets and therefore was used as an isotype control. When mAb 36 was utilized as an affinity matrix, bound proteins specifically inhibited CD3- LGL-K562 conjugation. Experiments involving tunicamycin treatment of tumor target cells demonstrated that mAb 36 recognized a carbohydrate moiety rather than the protein core. Therefore, these data suggested that the target cell recognition molecule which is recognized by mAb 36 appears to be a membrane carbohydrate-associated molecule. PMID- 1586959 TI - Induction of syngeneic cytotoxic T lymphocytes against a B cell tumor. I. Role of idiotypic immunoglobulin. AB - In previous studies we showed that idiotypic determinants of a B cell hybrid, 2C3, was involved in the generation of idiotype (Id)-specific noncytolytic CD4+ effector T cells that suppressed the Ig expression of wild type 2C3 tumor. In the present investigation we report that Id+ Ig associated with 2C3 was also capable of eliciting syngeneic cytotoxic T lymphocytes (CTL) when mice were hyperimmunized with irradiated 2C3 cells. These effector cells were predominantly Thy 1.2+, CD8+, and CD4- and highly cytotoxic to 2C3 as shown by in vitro and in vivo assays. The unique idiotypic determinants (private Id) of 2C3 Ig was important in the induction of CTL since these effector cells were generated in mice only after immunization with Id+ 2C3 cells. In contrast, immunization of mice with 6B2, an Ig-loss variant of 2C3, and 1BF7, an unrelated syngeneic B cell hybrid which expresses Ig of the same isotype as that of 2C3 but of different Id, failed to elicit any cytotoxic response. Furthermore, incorporation of anti idiotypic monoclonal and polyclonal antibodies into culture medium abrogated the activation of CTL during in vitro stimulation of the primed splenocytes. Induction of CTL was also inhibited by anti-MHC class I and anti-CD3 monoclonal antibodies, indicating that CD3-TcR complex of the effector T cells were involved in the recognition of Id+ Ig in the context of MHC class I antigens. These results, together with our previous observation, suggest that the anti-2C3 immune response is mediated by two kinds of effector cells, namely, CD4+ noncytolytic and CD8+ cytotoxic T cells. Moreover, the unique private Id associated with 2C3 plays a pivotal role in the induction of both of these effector cells. PMID- 1586960 TI - Anti-inflammatory properties of estrogen. I. In vivo suppression of leukocyte production in bone marrow and redistribution of peripheral blood neutrophils. AB - We have recently demonstrated that estrogen has differential immunomodulatory properties in mice because it stimulates antibody responses but inhibits T cell mediated inflammation. In the present study we have examined the influence of estrogen on T cell-independent inflammatory responses. A local inflammation was induced by intradermal injection of olive oil and cholera toxin. Treatment of castrated mice with pharmacological and even physiological doses of estradiol significantly suppressed the inflammatory response, as measured by footpad swelling and documented by histologic examination. Even a single injection of a low dose of estradiol (3.2 micrograms/mouse) given up to 4 days prior to the administration of the phlogistic compound reduced the inflammatory response. Our results demonstrate that the mechanisms whereby estrogen exerts its anti inflammatory property are probably not mediated by modulation of corticosteroid production. Instead, it is evidenced that estrogen significantly suppresses the bone marrow production of leukocytes and affects the distribution of polymorphonuclear cells in peripheral blood. The possible implications of our results are discussed in the context of the modulation of inflammatory rheumatic diseases. PMID- 1586961 TI - Induction of IL-2 receptor expression and proliferation of T cell clones by a novel cytokine(s). AB - We found a unique T cell IL-2 receptor (IL-2R)3-inducing activity in the supernatant (SN) of the TH1 clone stimulated with antigen on spleen cells as antigen-presenting cells (APC). We have tentatively named this activity the IL-2R inducing factor (IL-2RIF) and have characterized the activity. The SN induced IL 2R and proliferation of TH1 clones stimulated with B cell APC, which could not induce IL-2R in the absence of the SN. Other known cytokines were examined for a IL-2RIF activity; however, none of cytokines examined exerted a similar activity. Moreover, the neutralizing antibodies against the known cytokines tested did not block the IL-2RIF activity in the SN. When TH1 clones were stimulated with immobilized anti-CD3 or with fixed B cell APC in the presence of partially purified IL-2RIF, these clones expressed IL-2R and showed IL-2-dependent proliferation, whereas they induced neither IL-2R expression nor proliferation in the absence of IL-2RIF activity. These observations suggest that IL-2RIF activity is mediated by a novel cytokine(s) and the cytokine plays an important role as a second signal in the activation of the TH1 clone. PMID- 1586962 TI - Inability of IL-2 and IL-10 to counteract B cell clonal deletion. AB - The B cell antigen receptor (BCR) delivers inhibitory signals in nascent B cells leading to the establishment of tolerance via clonal deletion or clonal anergy depending upon the type of antigen to which the B cells are exposed. In previous work, it has been demonstrated that activated Th2 cells, as well as some recombinant lymphokines, prevent the inhibition of growth and subsequent cell death induced through the BCR in model B cell lymphomas. Herein, we extend this work to another Th2 lymphokine, IL-10, that in contrast to IL-4 does not interfere with the deletion promoted by IgM crosslinking. The effect of individual lymphokines has also begun to be analyzed in a transgenic model of B cell clonal deletion. To this end, we have administered a recombinant vaccinia virus producing human IL-2 to mice expressing an autoreactive H-2Kk,b-specific transgenic IgMk and found that IL-2 does not abrogate B cell deletion in vivo. PMID- 1586963 TI - Different intracellular localization of peroxisomal proteins in fibroblasts from patients with aberrant peroxisome assembly. AB - We investigated intracellular localization of peroxisomal proteins in fibroblasts from patients with Zellweger syndrome and neonatal adrenoleukodystrophy in whom peroxisomes were morphologically deficient or severely decreased. Indirect immunofluorescence staining revealed that catalase was mainly detected in the cytosol of fibroblasts from these patients, but a small amount of catalase was detected in granular pattern in a small percentage of cells. Double immunofluorescence staining revealed that catalase-containing particles in these patients also contained acyl-CoA oxidase and nonspecific lipid transfer protein. However, a 70 kD integral membrane protein and 3-ketoacyl-CoA thiolase were detected in all cells in granular pattern. Subcellular fractionation using digitonin after cell labeling revealed that a small amount of acyl-CoA oxidase and about half of thiolase in the precursor form were detected in the particulate fraction. These data suggest that the mechanisms of the transport and processing of catalase, acyl-CoA oxidase and nonspecific lipid transfer protein are different from those of the 70 kD integral membrane protein and 3-ketoacyl-CoA thiolase. PMID- 1586964 TI - Induction of DNA synthesis by fibroblast growth factor in temperature-sensitive cell-cycle mutants of rat 3Y1 fibroblasts arrested at restrictive temperature. AB - Four temperature-sensitive cell-cycle mutants of rat 3Y1 clonal fibroblasts representing separate complementation groups (3Y1tsD123, 3Y1tsF121, 3Y1tsG125 and 3Y1tsH203) are arrested at restrictive temperature, primarily with a G1-phase DNA content (temperature arrest). We examined various factors affecting signal transduction for activity which induces DNA synthesis at the restrictive temperature when added to the temperature-arrested cultures of these mutants. The factors examined were theophylline, dibutyryl cyclic AMP, cholera toxin (CT), dibutyryl cyclic GMP, sodium nitroprusside, phorbol 12-myristate 13-acetate, 1 oleoyl 2-acetylglycerol, bombesin, vasopressin, basic fibroblast growth factor (FGF), platelet-derived growth factor, A23187, monensin, epidermal growth factor (EGF), insulin and fetal calf serum (FCS). None of these factors induced DNA synthesis in 3Y1tsH203. In one mutant (3Y1ts121), FGF, EGF and FCS individually induced DNA synthesis. In the other 2 mutants (3Y1tsD123 and 3Y1tsG125), FGF and CT individually induced DNA synthesis. The FGF-induced DNA synthesis was suppressed by islet-activating protein (IAP) in 3Y1tsD123 and 3Y1tsG125, but not in 3Y1tsF121. The CT-induced DNA synthesis was also suppressed by IAP, as previously shown. When temperature-arrested cultures were shifted to a permissive temperature, all 4 mutants initiated DNA synthesis in the presence of IAP. These results suggest that (1) a cell can prepare for the initiation of DNA synthesis by using several independent signal transduction pathways, and (2) in a given situation, the cell uses a particular pathway because of its availability, which depends on the culture conditions. PMID- 1586965 TI - Electron microscopic observations on the maintenance of the tight junction during cell division in the epithelium of the mouse small intestine. AB - Dividing epithelial cells in the mouse small intestine were examined by thin section electron microscopy with special attention given to the mode of cytokinesis. As the columnar epithelial cells entered mitosis in the crypt, they became rounded, maintaining their junctional complexes with neighboring cells while detaching themselves from the basal lamina. In such rounded cells the mitotic apparatus was formed with its long axis parallel to the luminal surface. Replicated centrioles moved down from the apical region to locate themselves lateral to the nucleus, where they served as the poles of the mitotic spindle. During mitosis the cell retained microvilli on its luminal surface, though the terminal web became much thinner. At telophase the formation of a cleavage furrow proceeded asymmetrically from the basal side alone, and thus the contractile ring which was prominent at the base of the furrow, merged with the terminal web. Eventually, an intercellular bridge with a midbody was formed on the luminal surface. The space in the furrow was occupied by the flattened cytoplasmic processes of the neighboring cells. The tight junction was also seen on the basolateral surface of the intercellular bridge with the underlying neighboring cells. At very late telophase the intercellular bridge was disconnected from the neighboring cells and protruded into the lumen. These observations have led us to propose a mode by which the simple columnar epithelium maintain the tight junctional seal during cell division in the crypt of the small intestinal epithelium. PMID- 1586966 TI - The KKRKK sequence is involved in heat shock-induced nuclear translocation of the 18-kDa actin-binding protein, cofilin. AB - The exposure of cultured mammalian cells to elevated temperatures induces the translocation of actin and cofilin into the nuclei and the formation of intranuclear bundles of actin filaments decorated by cofilin (actin/cofilin rods). Cofilin has a stretch of five basic amino acids, KKRKK, which was assumed to be the sequence involved in the heat shock-dependent accumulation of cofilin in nuclei. To examine this possibility, the site-directed mutagenesis technique was employed to alter the KKRKK sequence of cofilin to KTLKK and the mutated cofilin was expressed under the human beta-actin promoter in transfectants of mouse C3H-2K cell line. All the recombinants derived from porcine cofilin cDNA were constructed so as to possess an extra-nonapeptide at their N-termini when expressed; their intracellular distribution could, therefore, be discriminated from that of endogenous cofilin using the indirect immunofluorescence method with polyclonal antibodies directed against the extra-peptide. The results clearly showed that the mutated cofilin possessing KTLKK instead of KKRKK did not translocate into the nuclei in response to heat shock whereas a recombinant cofilin with the unaltered sequence of KKRKK responded to heat shock and formed intranuclear rods together with actin. Although in vitro actin binding experiments showed that KTLKK-cofilin has a weaker affinity to actin filaments than KKRKK-cofilin, KTLKK-cofilin was found to form cytoplasmic actin/cofilin rods when transformants were incubated in NaCl buffer. Furthermore, we have noted that endogenous cofilin present in cells expressing KTLKK-cofilin behaved normally, translocated into nuclei and formed intranuclear actin/cofilin rods upon heat shock. These results suggest that the KKRKK sequence of cofilin functions as a nuclear location signal upon heat shock. PMID- 1586967 TI - A method for accurate analysis of intermembrane space in organelles enclosed by double envelope membranes. AB - Centrifugal filtration through a double layer of silicone oil was applied to determine the intermembrane space of organelles enclosed by double envelope membranes, i.e. proplastids, chloroplasts, mitochondria and amyloplasts. The organelles, capable of transporting adenylates by an adenylate translocator located in the inner envelope membrane, were incubated with increasing concentrations of adenylates while maintaining their specific radioactivities constant. Intermembrane spaces were estimated by extrapolation of radioactivities recovered after filtration of the organelles. The values estimated were compared to those obtained employing the classical method measuring the intake of [14C] sucrose and [14C]-sorbitol which are impermeable to the inner membranes of organelles. The intermembrane space determined by the present method was shown to be uniformly smaller than the sucrose-permeable space which was always smaller than the sorbitol-permeable space. PMID- 1586968 TI - Intracellular localization of the HLA class II gene products in transfected mouse L cells. AB - To investigate the impaired cell surface expression of human major histocompatibility antigen (HLA) in transfected L cells, we examined their intracellular localization by immunocytochemistry. HLA class II molecules produced in transfected L cells were mainly detected in the intracellular vesicles and in the nuclear envelope as granular precipitates. The results suggest that the intracellular transport of the newly synthesized molecules in transfected L cells is impaired at some point along the pathway from the rough endoplasmic reticulum (RER) to the medial-, trans-Golgi apparatus. PMID- 1586969 TI - Evidence for fluid-phase pinocytosis of extrahepatic bile duct cells isolated from normal rats in culture. AB - In order to elucidate the physiological function of extrahepatic bile duct cells, we isolated epithelial cells from the rat extrahepatic bile duct by digesting resected segments of the extrahepatic bile duct with 0.15% trypsin in ice-cold Ca(2+)-free Hanks' balanced salt solution supplemented with 0.25 mM EDTA overnight. As a result, the epithelial cells were collected as aggregates and attached to culture dishes coated with type I collagen. Approximately 95% of the cells cultured for 24 hrs were found to be positive for gamma-glutamyl transpeptidase and cytokeratin-19, but negative for vimentin. These characteristics were identical to the features of rat extrahepatic biliary epithelial cells in situ. Ultrastructurally, the cells were long and columnar in configuration on the 2nd day in culture, and possessed numerous microvilli at the apical surface and well-developed junctional complexes at the lateral surface. These findings also indicate that the cells maintain an epithelial nature and are morphologically polarized. When the cells were exposed to a low dose of horseradish peroxidase (HRP) on the 2nd day in culture, which was followed by fixation and treatment with 3-3'-diaminobenzidine, HRP was found preferentially in the cytoplasmic vesicles near the apical surface. HRP was then observed in the intercellular spaces; however, the electron-dense tracer, ruthenium red, did not permeate into the intercellular spaces, and HRP was found in neither cytoplasms nor intercellular spaces when the cells were incubated in HRP-containing medium at 4 degrees C for 30 min. These results suggest that the extrahepatic bile duct epithelial cells are involved in the reabsorption of bile constituents. PMID- 1586970 TI - Intracellular localization and partial amino acid sequence of a stress-inducible 40-kDa protein in HeLa cells. AB - We earlier discovered a novel 40-kDa protein (hsp40) induced by heat shock and other stresses in mammalian and avian cells. In this report, we purified the hsp40 in HeLa cells, using modified two-dimensional gel electrophoresis, and determined the amino terminal amino acid sequence of this protein. The hsp40 is homologous to DnaJ, an Escherichia coli heat-shock protein, as well as to DnaJ homologous proteins in yeast such as SCJ1, Sec63/Np11, YDJ1 and SIS1. Indirect immunofluorescence staining using an anti-hsp40 polyclonal antibody demonstrated that hsp40 was localized faintly throughout the cell in non-heat-shocked cells and was accumulated in nuclei and nucleoli in heat-shocked cells. The intracellular localization of hsp40 was very similar to that of hsp70, suggesting that these two hsps colocalize in heat-shocked HeLa cells. PMID- 1586971 TI - Roles of various growth factors in growth of human osteosarcoma cells which can grow in protein-free medium. AB - The human osteosarcoma cell line (OST-1-PF) can grow in protein-free Coon's modified Ham's F12 medium. Growth of the cells in protein-free medium was partially density-dependent and partially depressed by medium change. An extract and conditioned medium of OST-1-PF cells contained high mitogenic activity for BALB/c3T3 cells. The growth factor in the cells was purified and identified as a basic fibroblast growth factor (bFGF)--like factor on the basis of its elution profile on heparin-affinity chromatography and the result of immunoblotting. An unidentified factor in a conditioned medium eliciting most of the DNA synthesis stimulating activity showed a weak affinity for heparin. Various additions, including serum and growth factors, stimulated the growth of OST-1-PF cells in protein-free medium. Of these factors, epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), acidic fibroblast growth factor (aFGF) and bFGF were the most potent mitogens. High-affinity receptors of EGF and FGF were found on the surface of these cells. These results indicate that autonomous growth of OST-1-PF cells in protein-free medium is mainly controlled by an intracellular mechanism. PMID- 1586972 TI - [The effect of ionizing radiation on enzymes. VI. The effect of gamma irradiation on the proteolytic activity of pepsin derived from porcine gastric mucosa]. AB - The present paper examines the effect of gamma radiation on the proteolytic effectiveness of pepsin of an activity of 6640, 8940 and 11,333 units in 1 g, expressed according to the Czechoslovak Pharmacopoeia. The samples were irradiated with graded doses from 5.2 to 128.7 kGy so that the course of inactivation could be determined. Effectiveness was determined six times in each sample and parallel experiments were statistically evaluated. The results are shown in Tables 1 to 3. The relative width of the interval of reliability only exceptionally exceeds 5%. A decrease in effectiveness shown in Fig. 1 shows that the course of the decrease in effectiveness did not depend in the interval used on the initial activity of the enzyme. In the semilogarithmic arrangement in Fig. 2, the dependence of the decrease in effectiveness on the dose possesses a linear course. The decrease in effectiveness in dependence on the dose of radiation can be approximately read in the graph in Fig. 3. The Czechoslovak Pharmacopoeia prescribes a dose of 24 kGy to achieve sterility by means of ionizing radiation. When microbiological indefectibility is the case, a smaller dose suffices, depending on the level of the initial contamination and the resistance of the present microorganisms. It usually does not exceed 10 kGy, in our case even 5 kGy. Nevertheless, there occurs a loss of effectivity, in the extreme case 10 13%. The largest dose used in the present paper decreased effectiveness by 60%. If ionizing radiation is to be used to decontaminate pepsin, a certain decrease in activity must be taken into account. In addition, a toxicological evaluation must be recommended. PMID- 1586973 TI - [Precursor drugs 1980-1990]. PMID- 1586974 TI - [Preparation of a prekallikrein concentrate and determination of its activator in blood derivatives]. AB - The determination of an increased level of a fragment of the Hageman's factor (HFf) in preparations prepared from blood plasma can be an index of their potential reactivity in clinical application. The demonstration of the presence of HFf is based on the fact that the preparation containing this factor is able to activate the prekallikrein substrate. When the concentration of prekallikrein is sufficient, the amount of the developed active enzyme kallikrein is proportional to the amount of HFf. The amount of kallikrein is determined by cleaving the specific chromogenic substrate NO-Pro-Phe-Arg-pNA. The presence of salts negatively influences the rate of the activating stage of the reaction. The described preparation of the prekallikrein concentrate from the human blood plasma is a modification of the method of Levy and Sober) for the separation of the human immunoglobulin fraction. The blood plasma with an addition of hexadimethrinebromide is sorbed on DEAE Sephadex equilibrated with 0.0175 mol/l phosphate buffer pH 6.3 with hexadimethrinebromide in a vessel with an intact surface. Prekallikrein together with IgG are not sorbed on the anion exchanger under the above-mentioned conditions. The obtained supernatant can be employed as the prekallikrein substrate to determine the HFf activity in blood derivatives. PMID- 1586976 TI - Cerebrospinal fluid pharmacokinetics of carboplatin in children with brain tumors. AB - The pharmacokinetics of carboplatin in cerebrospinal fluid (CSF) and plasma was studied in five children with brain tumors (four medulloblastomas and one ependimoblastoma) who underwent preirradiation treatment with carboplatin. Carboplatin pharmacokinetics was studied following the administration of 600 mg/m2 as a 1-h infusion. Four children were treated a few weeks after surgery, whereas one child with an unresectable tumor was treated prior to surgery. All patients had a ventricular-peritoneal CSF shunt connected to a subcutaneous reservoir. Total platinum and free carboplatin were measured. The mean AUC values for free carboplatin in CSF and plasma were 2.29 +/- 1.20 and 8.18 +/- 1.27 mg ml 1 min, respectively. The mean ratio of CSF AUC to plasma AUC was 0.28 (range, 0.17-0.46). Both plasma peak levels and AUC values showed limited interpatient variability. On the other hand, carboplatin levels in CSF showed substantial interpatient variability, with a greater than 5-fold difference in peak levels and a 3-fold difference in AUC values being recorded. The interpatient difference in CSF pharmacokinetics may have been related at least in part to the different anatomical alterations induced by the surgical procedures or by the presence of a large tumor mass. In the four evaluable patients exhibiting macroscopic residual tumor, we observed one complete remission (CR) and two partial remissions (PR) following two cycles that consisted of two doses of 600 mg/m2 carboplatin given on 2 consecutive days (total dose, 1200 mg/m2) and were separated by a 1-month interval. These results may give some indication as to the optimal dose and schedule for carboplatin administration in the treatment of primitive neuroectodermic tumors (PNET). PMID- 1586975 TI - Posttranscriptional regulation of c-myc proto-oncogene expression and growth inhibition by recombinant human interferon-beta ser17 in a human colon carcinoma cell line. AB - Recombinant human interferon-beta ser17 (IFN-beta ser17), a cytokine that exhibits both antiviral and antiproliferative activity against a wide variety of cell types, causes a time- and dose-dependent inhibition of monolayer growth and of the expression of the c-myc proto-oncogene in DLD-1 Clone A human colon carcinoma cells. The suppression of c-myc expression mediated by IFN-beta ser17 is due to a posttranscriptional destabilization of c-myc mRNA rather than to an inhibition of c-myc mRNA transcription. There is evidence suggesting that the selective reduction in the half-life of c-myc mRNA in IFN-beta ser17-treated cells occurs through an increase in the activity of the 2',5'-oligoadenylate synthetase/RNase L [2',5'-oligo (A) synthetase] pathway in DLD-1 Clone A cells. Cotreatment of these cells with IFN-beta ser17 and the anticancer agent N methylformamide leads to the partial abrogation of 2',5'-oligo (A) synthetase activity and the stabilization of c-myc mRNA. These findings suggest that there is a correlation between the IFN-beta ser17-mediated suppression of c-myc expression and the induction of 2',5'-oligo (A) synthetase activity in DLD-1 clone A cells. PMID- 1586977 TI - Effects of 5-fluorouracil, leucovorin, and glucarate in rat colon-tumor explants. AB - In a previous study, we showed that 5-fluorouracil (FU) is active against the dimethylhydrazine-induced colon tumor in rats; a 7-day infusion of FU at 30 mg/kg daily produced 85% tumor-free cures. The present study examined the effects of FU alone and in combination with leucovorin (LV) or D-glucarate (GT) using an ex vivo system that maintained the growth of the rat colon-tumor explants on collagen gels. The labeling index (LI) was determined by the incorporation of [3H]-thymidine and autoradiography. The mean LI of the untreated control was 64.8% +/- 19.8%. The IC50, IC90, and IC95 values following a 7-day exposure to FU were 0.36, 0.75, and 1.22 microM, respectively. In comparison, the steady-state FU concentration required to produce 67% tumor-free cures in rats following a 7 day infusion is 1.54 microM. LV alone did not produce any antiproliferative effect at concentrations as high as 10 microM. The addition of LV at concentrations of 0.001-10 microM did not significantly reduce the IC50 of FU. The lack of effect of LV may have been due to tissue saturation with folate provided in the culture medium. GT alone reduced the tumor LI by 20%-30% at concentrations of 0.1-10 microM. GT enhanced the effect of FU. As compared with FU alone, the addition of GT at concentrations of 0.1 and 1.0 microM reduced the IC50 of FU by 47% and 60% to 0.21 and 0.16 microM, respectively. Assessment of the potentiation of the inhibitory effect of FU by GT using two-way analysis of variance and the isobologram method indicated a significant synergistic interaction between FU and GT. This interaction occurred within the FU concentration range of 0.08 and 0.4 microM. In summary, these data indicate that (a) the IC values for FU are comparable in tumor explants and in rats, suggesting that the effects in cultured tumors reflect those in intact animals; (b) GT alone showed antitumor activity, albeit relatively minor as compared with FU; (c) FU and GT exhibited synergistic activity, which was most pronounced at FU concentrations that produced submaximal activity (less than 30% inhibition of tumor LI); and (d) GT and LV had different effects on the growth inhibition by FU, suggesting that GT acts by a mechanism different from the thymidylate synthase-directed effect of FU and LV. PMID- 1586978 TI - In vitro evaluation of a novel chemotherapeutic agent, Adozelesin, in gynecologic cancer cell lines. AB - Adozelesin is a derivative of an extremely cytotoxic compound, CC1065. This entirely new class of drug binds preferentially to DNA and facilitates alkylation reaction. In the present study, we used the adenosine triphosphate (ATP) chemosensitivity assay to compare the cytotoxic potency of Adozelesin with that of common chemotherapeutic agents in ten gynecologic-cancer cell lines. Flow cytometry was also used to study its effects on cell-cycle kinetics. The mean drug concentrations required to produce a 50% reduction in ATP levels as compared with controls [IC50] were: Adriamycin, 0.17 +/- 0.06 microM; 4OH-Cytoxan, 18 +/- 3 microM; cisplatin, 17 +/- 7 microM; 5-fluorouracil, 183 +/- 116 microM; and Adozelesin, 11.0 +/- 5.4 pM. Thus, Adozelesin was 10(4) - 10(7) times more potent than Adriamycin, cisplatin, 5-fluorouracil, and Cytoxan. Cell kinetics studies revealed significant S and G2 blocks such as those previously reported for other alkylating agents. PMID- 1586979 TI - Human ovarian-carcinoma cell lines and companion xenografts: a disease-oriented approach to new platinum anticancer drug discovery. AB - A disease-oriented approach to the discovery of novel platinum anticancer drugs has been established through the setting up of parallel human ovarian-carcinoma cell lines and xenografts. The correlation between in vitro and in vivo antitumour activity was determined for four reference platinum agents (cisplatin, carboplatin, iproplatin and tetraplatin) in eight companion lines. Two methods of assessing antitumour effect were used in vitro (tritiated thymidine incorporation and sulforhodamine B staining) and three were applied in vivo [28-day treated/control (T/C) ratio, growth delay and specific growth delay]. In vitro, large differences in cytotoxicity across the cell lines were observed for each drug. This was also reflected in the xenografts for cisplatin and carboplatin and, to a lesser extent, for iproplatin. A correlation analysis of in vitro vs in vivo data revealed a high, statistically significant positive correlation for cisplatin and a strong positive correlation for carboplatin. However, for the two platinum(IV) drugs, the correlation was less good. In particular, tetraplatin was markedly less active in vivo (showing a general lack of activity against all of the tumour lines) than its in vitro potency against the cell lines predicted, resulting in poor correlation coefficients. These human tumour panels may be valuable for the elucidation of both cellular/molecular and corresponding in vivo pharmacological mechanisms of platinum drug resistance. Moreover, the HX/62 and SKOV-3 tumour lines, which exhibit a level of intrinsic resistance to the four reference agents both in vitro and in vivo (and which were derived from patients who had not received prior platinum therapy), represent particularly useful evaluation models for the discovery of novel broad-spectrum platinum drugs. PMID- 1586980 TI - Anthracyclines and their C-13 alcohol metabolites: growth inhibition and DNA damage following incubation with human tumor cells in culture. AB - Anthracyclines are important antitumor agents used in the treatment of solid tumors, lymphomas, and acute lymphoblastic as well as myelocytic leukemias. The clinical utility of agents such as doxorubicin and daunorubicin and their well characterized cardiotoxicity have prompted many efforts to develop analogs that retain the desired spectrum of activity but are less cardiotoxic. One such analog is idarubicin (4-demethoxydaunorubicin), which is currently under study in the treatment of adult and pediatric leukemias. The major circulating metabolite of idarubicin is the alcohol product of ketoreductase biotransformation, idarubicinol. Following the administration of idarubicin to adult or pediatric patients, systemic exposure to idarubicinol is greater than that to idarubicin. Moreover, we have also documented the presence of idarubicinol in the cerebrospinal fluid of pediatric patients who have received idarubicin. Idarubicinol has been reported to have greater cytotoxic activity than other anthracycline alcohol metabolites, which are regarded as much less active products of metabolism. We therefore evaluated the growth-inhibitory and DNA damaging activities of idarubicin, daunorubicin, doxorubicin, epirubicin, and their alcohol metabolites against three relevant (CCRF-CEM lymphoblastic leukemia, K562 myelogenous leukemia, and U87-MG glioblastoma) human tumor cell lines. We found that whereas idarubicin was 2-5 times more potent than the other three anthracycline analogs against these tumor cell lines, idarubicinol was 16 122 times more active than the other alcohol metabolites against the same three cell lines. In addition, idarubicinol and the parent drug idarubicin were equipotent, unlike the other anthracycline alcohol metabolites, which were much less cytotoxic than the corresponding parent drugs. We also assessed the ability of the four parent drugs and their alcohol metabolites to induce DNA single strand breaks. Idarubicin was more potent than the other three anthracycline analogs and idarubicinol was much more effective than the other alcohol metabolites in inducing DNA damage. These studies in human leukemia and human glioblastoma cell lines support the hypothesis that idarubicinol plays an important role in the antitumor activity of idarubicin and that the activities of idarubicin and idarubicinol are related to their ability to damage DNA. PMID- 1586981 TI - The protective activity of ICRF-187 against doxorubicin-induced cardiotoxicity in the rat. AB - The protective activity of the bisdioxopiperazine ICRF-187 against the cardiotoxicity of doxorubicin was evaluated in the rat using both functional and histological assays. Animals that had received a single i.v. dose of doxorubicin (4 mg/kg) alone were compared with those that had been pretreated with a single i.v. injection of saline or ICRF-187 (40 or 60 mg/kg). All rats showed a transient reduction in body weight during the first 3 weeks after drug administration. The greatest reduction (approximately 16%) was observed in animals that had received a combination of ICRF-187 (40 or 60 mg/kg) and doxorubicin. Deaths related to cardiotoxicity were observed only in rats that had received doxorubicin alone and in those treated with saline; most of the deaths occurred at between 8 and 13 weeks after drug administration. Sequential assessments of heart function showed a persistent depression of cardiac output in animals that had received doxorubicin, with or without pretreatment with ICRF 187. The reduction in cardiac output observed in rats that had been pretreated with ICRF-187 (40 or 60 mg/kg) amounted to approximately 15% and approximately 30% after 12 and 20 weeks, respectively, indicating that cardioprotection was only partial. Nevertheless, this represented a marked improvement as compared with the approximately 35% reduction in cardiac output measured at 12 weeks in animals that had received doxorubicin but without pretreatment with ICRF-187. Histological examination of animals that had died during the course of the study and had received doxorubicin after pretreatment with saline revealed severe myocardial lesions typical of doxorubicin-induced damage. In contrast, animals that had been pretreated with ICRF-187 and survived for up to 20 weeks after treatment showed a marked amelioration of these lesions. The present findings may be interpreted as a true cardioprotection or a delay in the onset of the cardiotoxicity of doxorubicin resulting from pretreatment with the bisdioxopiperazine ICRF-187. Although prior and ongoing clinical trials clearly indicate that ICRF-187 protects patients well against doxorubicin-induced heart damage, further investigations are required before high doses of ICRF-187 can be used as a means of increasing the protective activity of this drug against doxorubicin-induced cardiotoxicity. PMID- 1586982 TI - Factors influencing the inhibition of repair of irradiation-induced DNA damage by 2'-deoxycoformycin and deoxyadenosine. AB - Permeabilized L5178Y cells were used to investigate the mechanism underlying inhibition of the repair of irradiation-induced DNA strand breaks by 2' deoxycoformycin combined with deoxyadenosine. Permeabilized cells repaired DNA strand breaks as effectively as did intact cells, and at deoxyadenosine concentrations that produced similar levels of deoxyadenosine triphosphate (dATP), repair of DNA strand breaks was inhibited by 2'-deoxycoformycin plus deoxyadenosine to a comparable extent in both types of cells. Accompanying the increase in intracellular dATP produced by 2'-deoxycoformycin combined with deoxyadenosine was a fall in levels of deoxythymidine triphosphate (dTTP), deoxyguanosine triphosphate (dGTP), and deoxycytidine triphosphate (dCTP). The addition of dTTP, dGTP, and dCTP reversed the inhibition of DNA repair by 2' deoxycoformycin plus deoxyadenosine, although the level of dATP was not affected. Reducing the phosphorylation of deoxy-adenosine to dATP by the addition of adenosine prevented the decrease in levels of dTTP, dGTP, and dCTP and the inhibition of DNA repair by 2'-deoxycoformycin and deoxyadenosine. In contrast, increasing the intracellular levels of dATP by the addition of 2'-deoxycoformycin together with dATP, deoxyadenosine diphosphate (dADP), or deoxyadenosine monophosphate (dAMP) had no effect on the levels of the other deoxynucleotide triphosphates and did not inhibit DNA repair. Moreover, DNA repair was not inhibited by the breakdown products of deoxyadenosine, adenine, or deoxyribose. These results suggest that inhibition of the repair of irradiation-induced DNA strand breaks by 2'-deoxycoformycin combined with deoxyadenosine requires the phosphorylation of deoxyadenosine and involves alterations in the levels of deoxynucleotide triphosphates. PMID- 1586983 TI - A new liver-tumor model in the rat. AB - A new tumor model for testing and comparing the effect of different forms of treatment on liver tumors is described. Single tumors were induced in the liver of rats by the implantation of small pieces taken from a subcutaneously growing tumor. Tumor growth was determined by measuring the weight of the implanted tumors after the animals had been killed. In this way, weight curves for treated and untreated tumors could be defined. The weight of untreated liver tumors increased exponentially with time (tumor weight in milligrams = 1 + e(t-0.31)/5). In addition, tumor growth defined as the geometric mean of three perpendicular diameters was determined. Tumor-diameter curves showed a linear increase with time in the untreated groups (tumor diameter in millimeters = 0.4 t + 1.90). The model was tested by assessing the effect of intraperitoneally injected cisplatin. The dose chosen produced a marked delay in tumor growth. On the basis of the weight gain shown by the treated animals and tumor growth delay, a therapeutic index can be defined, thus enabling to compare quantitatively different forms of treatment according to their antitumor effect and toxicity. PMID- 1586984 TI - A randomised phase II study of carmustine alone or in combination with tumour necrosis factor in patients with advanced melanoma. AB - Laboratory data suggest a synergistic interaction between carmustine (BCNU) and tumour necrosis factor (TNF) in melanoma. We therefore studied the activity of 200 mg/m2 BCNU given alone or in combination with 88 micrograms/m2 recombinant human TNF-alpha (rhTNF alpha) as a daily i.v. infusion for 5 days at 48-day intervals to patients with metastatic melanoma. In this randomised phase II trial, the rate of response to BCNU alone was 20% [95% confidence interval (CI), 2%-38%], and this was not improved by the addition of TNF (response rate, 10.5%; 95% CI, 1.3%-33%). Toxicity was higher in the combination arm, and there was no difference in survival. PMID- 1586985 TI - O6-Alkylguanine-DNA alkyltransferase content in synchronised human cancer cells. AB - The DNA repair enzyme O6-alkylguanine-DNA alkyltransferase (AT) was analysed in the human ovarian-cancer SW626 cell line and in the human promonocytic leukemia U937 cell line following their synchronisation with low non-toxic concentrations of methotrexate. In SW626, AT increased in the early S phase of the cell cycle and then declined during progression of the S phase to levels found in the G1 phase of unsynchronised cells. In contrast, at the G1/S-phase boundary and in the S phase, U937 cells showed a lower AT content than did exponentially growing unsynchronised cells. In addition, AT activity was greatly reduced in resting U937 cells but was not reduced appreciably in resting SW937 cells but was not reduced appreciably in resting SW626 cells. The results of these studies indicate that AT fluctuations do not follow a constant pattern during the cell cycle of different cell lines. PMID- 1586986 TI - The role of the stages of initiation and promotion in phenotypic diversity during hepatocarcinogenesis in the rat. AB - Differences in the distribution of phenotypic alterations in initiated and promoted cell populations reflect both the dose and the action of the specific initiating agent, as well as the mechanism of action of the promoting agent. The use of multiple phenotypic markers to characterize AHF should allow further experimentation on the characteristics of promoting agents in hepatocarcinogenesis, especially their ability to promote separate populations of initiated cells, and on those characteristics of initiated cells that enable certain ones to survive and multiply in the specific environment provided by a promoting agent. Studies of promoting agents with differing mechanisms of action should further allow questions of reversibility, substitution and additivity of the actions of promoting agents to be addressed. The possibility that individual promoting agents do not enhance the growth of the entire population of initiated cells indicates that study of combinations of promoting agents is an important future direction of research. Therefore, information on the characteristics of promoting agents, singly and in combination, is necessary to assess more accurately the contribution of promoting agents to the carcinogenic risk for humans distinct from the effects of initiating agents and complete carcinogens. PMID- 1586987 TI - N-acetylated and deacetylated 4'-fluoro-4-aminobiphenyl and 4-aminobiphenyl adducts differ in their ability to inhibit DNA replication of single-stranded M13 in vitro and of single-stranded phi X174 in Escherichia coli. AB - Calf thymus single-stranded (ss) DNA was modified with the N-sulfate conjugate of N-hydroxy-2-acetylaminofluorene (N-OH-AAF), N-hydroxy-4'-fluoro-4 acetylaminobiphenyl (N-OH-FAABP) or N-hydroxy-4-acetylaminobiphenyl (N-OH-AABP) to yield predominantly N-acetylated adducts of 2-aminofluorene, 4-aminobiphenyl and 4'-fluoro-4-amino-biphenyl respectively to C8 of deoxyguanosine (dG-C8-AAF, dG-C8-AABP and dG-C8-FAABP). The modified DNAs were used as templates for in vitro DNA synthesis. DNA replication on the randomly primed template was inhibited as compared to control (unmodified) DNA to the same extent by all three types of adducts, irrespective of whether polymerization was performed by Escherichia coli DNA polymerase I, modified T7 DNA polymerase or Thermus aquaticus (Taq) DNA polymerase. In addition, all three types of adducts completely blocked replication of ss phi X174 in an E. coli host: on average one adduct per DNA molecule was sufficient to inactivate the bacteriophage. Polyacrylamide gel electrophoresis of DNA fragments synthesized by E. coli DNA polymerase I on FAABP- and AABP-modified ss M13mp9 DNA templates, showed that termination occurred predominantly one nucleotide before (and occasionally opposite) a modified deoxyguanosine in the template. However, the deacetylated adducts, dG-C8-AF, dG-C8-ABP and dG-C8-FABP (obtained by reacting DNA with their N-trifluoroacetyl-N-acetoxy esters) were frequently bypassed during replication of ss phi X174 in E. coli, though with different efficiencies: 1 out 7, 1 out of 2 and 1 out of 3 adducts on average respectively caused bacteriophage inactivation. Polyacrylamide gel electrophoresis showed that termination of DNA synthesis occurred at least as frequently opposite as 3' to a modified deoxyguanosine in the template. PMID- 1586988 TI - Alkylation of rodent tissue DNA induced by N-nitrosobis(2-hydroxypropyl)amine. AB - Levels of methyl and hydroxypropyl adducts induced by single s.c. injections of various doses of tritium-labeled N-nitrosobis(2-hydroxypropyl)amine ([1-3H]BHP) were determined in the liver, pancreas, kidney and lung of hamsters and rats. At doses of BHP used in carcinogenesis studies (100-500 mg/kg), methylation of DNA was more extensive than its hydroxypropylation; however, it did not increase proportionally with the dose and gradually became secondary to hydroxypropylation at higher doses of the carcinogen. Ratios of hydroxypropyl versus methyl adducts also varied significantly depending on the tissue and species. In both species ratios of N7-hydroxypropylguanine (N7-HpG) versus N7-methylguanine (N7-MeG) were greater in kidney and pancreas than in liver or lung. Due to apparent differences in the repair of O6-methylguanine (O6-MeG) and O6-hydroxypropylguanine (O6-HpG), and the propensity of 2-hydroxypropylating as compared to methylating agents to yield a greater percentage of oxygen adducts, ratios of O6-HpG versus O6-MeG were markedly greater than those of N7-HpG versus N7-MeG. Levels of O6-HpG were greater than those of O6-MeG in rat liver, pancreas and kidney and also in hamster kidney, while such levels were similar in rat lung and also in hamster liver, pancreas and lung. Like N-nitrosobis(2-oxopropyl)amine (BOP) and N nitroso(2-hydroxypropyl) (2-oxopropyl)amine (HPOP), BHP was activated primarily in the liver and induced substantially greater DNA damage in this than in any other tissue examined. However, unlike BOP and HPOP, which induced similar levels of hepatic DNA damage in the above two species, BHP methylated and hydroxypropylated hamster liver DNA more extensively than that of the rat. Differences between BOP and BHP were also observed regarding levels and distribution of DNA adducts in extrahepatic tissues. In rats, BHP induced greater levels of methylation and hydroxypropylation in lung than in kidney, while the reverse was observed with BOP. Apparently reduction of the beta-carbon of pancreas-specific nitrosamine carcinogens results in a shift of alkylation from kidney to the lung. Excretion of HPOP in the urine of BHP-treated animals and the observed saturation of DNA methylation at high doses of BHP, supported the hypothesis that the BHP-induced methylation of DNA proceeded via the intermediate formation of HPOP. This was further supported by the observation that both excretion of HPOP and levels of methyl adducts were greater in hamsters than in rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1586989 TI - Tissue distribution of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) in two strains of male rats. AB - Albino and hooded male rats were administered 14C-labeled 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) by gavage. The tissue distribution was investigated by means of whole-body autoradiography and liquid scintillation counting. MeIQx was rapidly absorbed from the alimentary tract and distributed to several tissues. The major predilection sites were the liver and kidneys. The amount of radioactivity decreased dramatically within a few days. However, unextractable radioactive material was still detectable in these organs 6 days after the administration. PMID- 1586990 TI - Candida albicans as a promoter of oral mucosal neoplasia. AB - A model of oral mucosal carcinogenesis using the water-soluble carcinogen 4 nitroquinoline-1-oxide (4NQO) was combined with a model of oral mucosal candidosis to examine the ability of Candida albicans to promote the development of neoplasia in suitably initiated epithelium. Sprague-Dawley rats were initiated by the application of 4NQO to their palatal and tongue mucosa 3 times weekly for 4 weeks. The animals then received either application of a phorbol ester to act as a promoter, induction of experimental oral mucosal infection with C. albicans, or no further procedures. Animals were killed at 34 or 52 weeks and the tongues and palates sectioned for light-microscopic examination. Control groups with no treatment, mucosal infection only, phorbol ester application only, 4NQO with the tetracycline or vehicle application only were also used. The development of carcinoma in the experimental groups was similar to that in the positive control groups, indicating that the particular strain of Candida used had a similar ability to promote neoplastic changes as the known promoter phorbol-12,13 didecanoate and caused neoplastic changes to occur by week 34 with no additional lesions occurring by week 52. This indicated that the speculation that strains of C. albicans may participate in causing neoplastic transformation in humans was well founded. PMID- 1586991 TI - Enhancement of GST-P-positive liver cell foci development by nivalenol, a trichothecene mycotoxin. AB - In order to elucidate whether T-2 toxin (T-2) and nivalenol (NIV), the naturally occurring trichothecene mycotoxins in food and feed, are carcinogenic or possess an ability to modulate aflatoxin B1 (AFB1)-induced hepatocarcinogenicity, a medium-term liver bioassay was carried out. F344 male rats were given a single i.p. injection of diethylnitrosamine (DEN, 200 mg/kg), and then fed the test trichothecenes in diet (2 and 5 p.p.m. T-2 or 6 p.p.m. NIV) for 6 weeks beginning 2 weeks after the injection. Some control groups received DEN alone. For synergism between AFB1 and the trichothecenes, DEN-initiated rats as above were given a single i.p. injection of AFB1 (0.5 mg/kg) 2 weeks later and were fed a NIV-containing diet (6 p.p.m.) for 6 weeks. The other control group received the vehicle alone. Control rats not initiated with DEN were also treated with AFB1, NIV or T-2 alone as above. All rats were subjected to a two-thirds partial hepatectomy (PH) at week 3 and killed at week 8, and liver sections were analyzed by glutathione S-transferase placental form (GST-P) expression. In rats that did not receive DEN, AFB1 alone enhanced both the numbers and areas of GST-P-positive foci as reported earlier, while NIV or T-2 alone induced no marked changes. In rats initiated with DEN, AFB1 caused a marked expression of GST-P, and thus the hepatocarcinogenicity of AFB1 was reconfirmed. The expression of GST-P foci in rats fed T-2 or NIV was found to be at background level, indicating that the hepatocarcinogenicity was not predicted for the trichothecene mycotoxins such as T-2 and NIV by this medium-term bioassay system. In the group initiated by DEN followed by AFB1, on the other hand, an elevation of both the numbers and areas of GST-P-positive foci was observed by the subsequent feeding of rats with NIV, and this elevation was statistically significant from the sum totals of individual data of AFB1 or NIV alone. From this evidence, it is predicted that NIV causes an enhancing effect on AFB1-induced hepatocarcinogenesis. PMID- 1586992 TI - Induction of preneoplastic lesions by a low dose of 2-amino-3,8 dimethylimidazo[4,5-f]quinoxaline (MeIQx) in the livers of rats treated with carbon tetrachloride. AB - The multifactorial nature of carcinogenesis in man has impelled us to study the effects of various chemicals and conditions in combination. In the present investigation, we examined the effects of low doses of 2-amino-3,8-dimethyl imidazo[4,5-f]quinoxaline (MeIQx) in combination with carbon tetrachloride (CCl4) on the formation of glutathione S-transferase placental form (GST-P)-positive foci in rat liver. Administration of diet containing MeIQx at 0.4, 4 or 40 p.p.m., representing one-thousandth, one-hundredth and one-tenth of the dose proved to induce hepatocellular carcinomas (400 p.p.m.), for 8 or 12 weeks did not induce GST-P-positive foci. However, 40 p.p.m. of MeIQx when co-administered with CCl4 (0.7 ml/kg, s.c. twice a week) induced preneoplastic lesions: 7- and 3 fold increases in the numbers and areas of GST-P positive foci in week 8, and 8- and 6-fold increases respectively in week 12, over those with CCl4 alone. Furthermore, a marked increase in the number of hyperplastic nodules was observed in this group of rats in week 12. No significant increases of GST-P-positive foci were observed at doses of 0.4 or 4 p.p.m. MeIQx in combination with CCl4. Thus, it is predicted that chronic exposure to 40 p.p.m. of MeIQx eventually results in induction of hepatocellular carcinomas in injured rat liver. PMID- 1586993 TI - DNA sequence analysis of 1-nitrosopyrene-induced mutations in the hprt gene of Chinese hamster ovary cells. AB - DNA sequence was determined in 21 mutants induced at the hprt locus of Chinese hamster ovary (CHO) cells by 1-nitrosopyrene, a metabolite of the tumorigenic environmental pollutant 1-nitropyrene. Following cDNA synthesis using RNA from each of the mutants, the hprt protein-coding region was amplified by the polymerase chain reaction (PCR) and subjected to direct DNA sequence analysis. Sixteen primary mutations were found: seven were G:C----T:A transversions, five were G:C----A:T transitions, two were single basepair insertions, one was a single basepair deletion, and one was a complex mutation involving substitutions at two A:T basepairs. The simple basepair substitution mutations preferentially occurred with one or two purines 3' to the mutated dG, and mutations in exons 1-4 disproportionately occurred with the mutated dG on the nontranscribed DNA strand. In addition, 12 of the mutants produced one or more cDNA PCR products with partial or complete exon deletions. Seven mutants with multiple PCR products had point mutations in one of the products; exon deletions in the other product(s) removed these point mutations. A group of solvent control mutants had a different distribution of basepair substitution mutations and a lower proportion of cDNAs with exon deletions than that found for the 1-nitrosopyrene-induced mutants. The results indicate a specificity for the induction of mutations in the hprt gene of CHO cells by 1-nitrosopyrene with respect to both the types of mutations produced and their location in the hprt gene. Also, the elimination of point mutations in many of the cDNA PCR products with exon deletions suggests that mutations in the protein-coding sequence affect hprt mRNA processing. PMID- 1586994 TI - Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating. AB - A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine. PMID- 1586995 TI - In vivo formation of aflatoxin B1-DNA adducts in parenchymal and non-parenchymal cells of rat liver. AB - The induction of hepatocellular carcinoma from liver parenchymal cells in laboratory animals by aflatoxin B1 (AFB1) is well documented. In contrast no tumours arising from the sinusoidal cell population have been reported after exposure to AFB1. The apparent resistance of the latter cell type was investigated at the level of DNA adduct formation in vivo in male Sprague-Dawley rats. Liver parenchymal and non-parenchymal cell populations were isolated from rats at 20 min and 1, 24 and 72 h after administration of 240 microCi (0.6 mg) [G 3H]AFB1/kg. AFB1-DNA binding was observed in both liver cell subpopulations and was 3- to 5-fold higher in parenchymal cells than in non-parenchymal cells. The major DNA adduct found in parenchymal cells at 1 h after AFB1 administration was 8,9-dihydro-8-(N7-guanyl)-9-hydroxyaflatoxin B1 (AFB1-gua), whereas at later time points the persistent secondary adduct, AFB1-formamidopyrimidine, predominated. In contrast, AFB1-gua was not observed at any time in DNA from non-parenchymal cells and the secondary adducts predominated throughout. These observations are discussed with reference to the susceptibility of different liver cell types to AFB1-carcinogenesis and the possible roles of the major AFB1-DNA adduct species. PMID- 1586996 TI - Specific amino acid sequences required for O6-methylguanine-DNA methyltransferase activity: analyses of three residues at or near the methyl acceptor site. AB - O6-Methylguanine-DNA methyltransferase plays an important role in preventing tumor induction. To elucidate the significance of a highly conserved amino acid sequence of methyltransferase protein, amino acid substitutions were introduced by site-directed mutagenesis of cloned cDNA for human methyltransferase and the activity and stability of mutant forms of enzyme were examined. When cysteine 145, to which the methyl transfer occurs, was replaced by other amino acids, all of the mutants isolated showed the methyltransferase-negative phenotype. From one of the negative mutants, methyltransferase-positive revertants were isolated, all of which carried codons for cysteine. Thus the cysteine residue is essential for acceptance of the methyl group and cannot be replaced by other amino acids. Using this negative and positive selection procedure, analyses were extended to other residues near the acceptor site. At the histidine-146 site, four substitutions (phenylalanine, methionine, asparagine and glutamine) exhibited the positive phenotype but the levels of methyltransferase activity in these mutants were low. With valine-148 substitutions there were six types of positive revertants, among which mutants carrying isoleucine, cysteine and alanine showed significantly high levels of methyltransferase activity. Some mutant forms of cDNA were expressed in methyltransferase-deficient human cells, and the results obtained with Escherichia coli cells were confirmed. PMID- 1586997 TI - Growth and metastasis of fresh human benign and malignant tumors in the head and neck regions transplanted into scid mice. AB - Surgically resected fresh human tumors (16 malignant and 1 benign) in the head and neck regions were s.c. transplanted into scid mice. All malignant tumors (12 squamous cell carcinomas, 2 papillary adenocarcinomas and 1 adenoid cystic carcinoma) except one heavily irradiated squamous cell carcinoma could grow in scid mice. However, all of three squamous cell carcinomas of the maxillary sinus grew only in 50% of scid mice, and two of them failed to grow in the second transfer. The remainder were successfully transplantable for further generations, except one accidental case. A benign tumor, a follicular adenoma of the thyroid gland, was also accepted in scid mice and was transplantable for further generations, though its growth was very slow. Distant metastases were found in the lung only when poorly differentiated carcinomas were transplanted into scid mice, but did not occur until 90 days after the transplantation of well and moderately differentiated carcinomas. The histological characteristics of both malignant and benign tumors were retained well in all of the xenografts and metastatic lesions. Thus, scid mice seem useful to investigate not only the properties of benign and malignant human tumors but also the metastatic spread of tumors which threaten the life of cancer patients. PMID- 1586998 TI - Comparison of Ki-ras gene mutation among simultaneously occurring multiple urethan-induced lung tumors in individual mice. AB - Mouse lung tumors were induced in C57BL/6J(female) x A/J(male) F1 mice by a single s.c. injection of urethan. About 6 months later, multiple small-sized lung tumors were detectable in almost all mice. After a further 6 months, some of these tumors became larger than the rest. We examined whether there were any mutational differences among multiple lung tumors in a single mouse. Direct DNA sequencing of a separately amplified Ki-ras gene by polymerase chain reaction (PCR) was carried out with 25 DNA samples from multiple tumors in four mice. Twenty-four of 25 tumors (96%) had mutations at the codon 61 of the Ki-ras gene. The major mutations involved were either AT to GC transition (44%) or AT to TA transversion (44%) at the second base of codon 61. We compared the types of these gene mutations among the tumors from each of two mice from two different groups of siblings and then compared the two groups. Interestingly, in the first group of siblings, we detected CTA in 5/6 tumors in the first mouse and again CTA in 4/6 tumors in the second one. In the second group of siblings, we detected CGA in 5/7 tumors in one mouse and CGA again in 3/5 tumors in the second mouse. These results show that the pattern of Ki-ras codon 61 mutations in urethan-induced lung tumors is similar in tumors developing in siblings, suggesting that host factors have an effect on the carcinogen-induced mutational pattern. There was no major mutational difference between small and large tumors. The results suggested that other event(s) in addition to the mutation of the Ki-ras gene might play a role during the development of large-sized tumors. PMID- 1586999 TI - Formation and repair of O6-methylguanine and methylation of the Ha-ras proto oncogene by N-methyl-N-nitrosourea are not associated with mammary tumor resistance in the Copenhagen rat. AB - A high incidence of mammary adenocarcinomas is induced in sexually immature, female Buf/N rats by a single dose of N-methyl-N-nitrosourea (MNU). The Ha-ras gene is activated in a majority of these tumors. The Copenhagen (Cop) rat is completely resistant to mammary gland carcinogenesis by a number of carcinogens, including MNU. Here we show that MNU-treated Buf/N and Cop rats do not differ in the extent of formation and rate of repair of O6-methylguanine in DNA isolated from their mammary epithelial cells. Furthermore, we show that the transcriptional activities of the Ha-ras genes are similar in the mammary glands of Buf/N and Cop rats and that the extents of methylation by MNU of restriction fragments containing the Ha-ras gene from mammary gland DNA are not different for the two strains. Resistance of the Cop rat to mammary carcinogenesis, therefore, appears not to be due to a defect in the interaction of the carcinogen with the target DNA. PMID- 1587000 TI - Bioavailability of tobacco-specific N-nitrosamines to the snuff dipper. AB - Use of supercritical carbon dioxide extraction in the analysis of smokeless tobacco for tobacco-specific N-nitrosamines revealed the presence of higher levels of 4-(methylnitros-amino)-1-(3-pyridyl)-1-butanone (NNK) than had been determined with conventional methods. Whether human saliva may be similarly capable of releasing apparently bound NNK during chewing or snuff dipping was tested by incubating smokeless tobacco with enzymatically active saliva and with heat-treated saliva respectively. Enzymatically active human saliva was found to liberate up to twice the amount of the highly carcinogenic NNK than did heat treated saliva. This is of major consequence for the cancer risk assessment of snuff dippers and tobacco chewers. PMID- 1587001 TI - 1-C-glucuronidation of N-nitrosodiethylamine and N-nitrosomethyl-n-pentylamine in vivo and in primary hepatocytes from rats pretreated with inducers. AB - The organ specificity of the carcinogenic action of nitrosamines is partly explained by organ specific activation. The specificity might also be determined by conjugation of reactive intermediates in e.g. the liver. 14C-Labeled N nitrosodiethylamine (NDEA) a liver carcinogen and N-nitrosomethyl-n-pentylamine (NMPentA) which induces esophageal and nasal tumors were administered to rats or incubated with primary cells. Urine and cell extracts were separated by HPLC after addition of synthetic marker glucuronides and these were quantified by liquid scintillation counting. In urine of rats treated with NDEA 0.03% of administered nitrosamine was recovered as the O-glucuronide derived from N nitroso-1-hydroxyethylethylamine. In rats treated with NMPentA 2.86% was metabolized to the glucuronide at the methyl group. In hepatocytes of untreated rats 0.03% of the added NDEA was conjugated to the glucuronide, phenobarbital pretreatment induced this conjugation reaction 5-fold. Hepatocytes from untreated rats metabolized 1.2% of NMPentA to the primary glucuronide; after phenobarbital pretreatment this value increased to 1.6%. In hepatocytes from 3 methylcholanthrene-pretreated rats, 0.04% of NMPentA was metabolized to the glucuronide derived from N-nitroso-1-hydroxy-n-pentyl-methylamine, while 0.85% was derived from N-nitroso-hydroxymethyl-n-pentylamine. In hepatocytes from Aroclor-pretreated rats, 0.09% were pentyl conjugates and 1.1% methyl conjugates. The induction pattern and organ specificity of glucuronidation indicate that all three 1-hydroxy nitrosamines are conjugated by group II phenobarbital inducible UDP-glucuronosyltransferase activity. The lipophilicity of a nitrosamine seems to determine the extent of glucuronidation in hepatocytes and in vivo. No glucuronides derived from either NDEA or NMPentA were detectable in incubations with kidney cells, nor was the glucuronide of NDEA found in incubations with whole bladders. PMID- 1587002 TI - Promutagenic methylation damage in bladder DNA from patients with bladder cancer associated with schistosomiasis and from normal individuals. AB - Radioimmunoassays (RIAs) have been used to detect the promutagenic lesion O6 methyldeoxyguanosine (O6-MedG) in DNA isolated from the bladder tissues of Egyptian patients presenting with bladder carcinoma and concomitant schistosomiasis (bilharziasis), a parasitic disease known to be associated with the presence of N-nitrosamines in the urine. Alkylation damage was present in the DNA of the majority of the samples (44/46, 96%); 38 samples were of tumour tissue and 8 from uninvolved bladder mucosa. Levels of O6-MedG ranged from undetectable (ND; i.e. less than 0.01 mumol O6-MedG/mol dG) to 0.485 mumol/mol dG with an overall mean of 0.134 +/- 0.10 mumol/mol dG, including the two samples that were below the limit of detection. In contrast, methylation damage was detected in only 4/12 (33%) of the DNA samples from normal bladder tissue of European origin. In these samples levels of O6-MedG ranged from ND to 0.225 mumol/mol dG with an overall mean of 0.046 +/- 0.082 mumol O6-MedG/mol dG. These results confirm that alkylation events can be detected in the DNA of schistosome-infected human bladder tissue. The methylation of uninvolved and tumour tissue DNA to similar extents suggests that the alkylating intermediate may have been present in the urine. These results indicate the need for further investigation to determine whether relationships exist between levels of DNA damage and the prevalence of schistosome infection and/or the extent and type of bacterial infection that frequently accompanies this disease. PMID- 1587003 TI - Tumorigenic activity of a rearranged c-myc gene from a human T-cell leukemia line. AB - The T-lymphoma cell line Hut78 contains a rearranged c-myc oncogene derived from a translocation between the long arms of chromosomes 8 and 2; the event deletes the 3' end of the gene, causing the loss of the transcribed AT-rich sequence. It has recently been shown that the mutant c-myc mRNA is several-fold more stable than normal c-myc mRNA. We have assessed the tumorigenicity of the mutant c-myc allele by transfecting this gene and its normal counterpart into NIH3T3 cells, together with a neomycin resistance gene. Following selection for G-418 resistance, the cells were injected into nude mice. Tumors containing integrated c-myc arose in animals injected with cells transfected by the mutated, but not by the normal, allele. The results suggest that this rearranged c-myc bears a tumorigenic activity not observed in other naturally occurring mutated c-myc alleles and may have directly contributed to the tumorigenic event in the Hut78 cell line. PMID- 1587004 TI - Aflatoxin M1 in human breast milk from The Gambia, west Africa, quantified by combined monoclonal antibody immunoaffinity chromatography and HPLC. AB - Maternal to child exposure of aflatoxin M1 in breast milk is an underevaluated risk factor from dietary exposure to aflatoxin B1. A molecular dosimetry study in The Gambia, West Africa, was initiated to explore the relationships between dietary intake of aflatoxins during a 1 week period and a number of aflatoxin biomarkers including aflatoxin metabolite excretion into breast milk. For the breast milk study, five lactating women were identified and milk samples were collected by hand expression once a day during days 3-7 for three women and during days 3-6 for the two other women. Aflatoxin M1 (AFM1) in human milk was measured in all five subjects by a preparative monoclonal antibody immunoaffinity column/HPLC method. In three of the five women, aflatoxin G1 was found. Estimates of the percentage of aflatoxin in the diet excreted as AFM1 in milk ranged from 0.09 to 0.43%. Thus, these data indicate that a rapid methodology exists to assess the levels of AFM1 excretion in human milk and to use this approach as a biomarker for exposure of children to this carcinogen. PMID- 1587005 TI - High selectivity of polyclonal antibodies against DNA modified by diastereomeric benzo[c]phenanthrene-3,4-diol-1,2-epoxides. AB - Polyclonal antibodies were developed in New Zealand White rabbits against DNA modified with diastereomeric benzo[c]phenanthrene-3,4-diol-1,2-epoxide (B[c]PhDE) 1 (4-hydroxyl and epoxide cis) and B[c]PhDE-2 (4-hydroxyl and epoxide trans). Antiserum developed against B[c]PhDE-2-DNA was stereoselective. In competitive ELISA assays using wells coated with 160 fmol B[c]PhDE-2-DNA adducts, B[c]PhDE-2 DNA gave 50% inhibition at 200 fmol adducts/well. B[c]PhDE-1-DNA required a 10 fold higher amount of adducts/well to give 50% inhibition. Benzo[a]pyrene-7,8 diol-9,10-epoxide-2-DNA and 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1 DNA caused only a 30% inhibition even at the highest doses tested (greater than 4000 fmol adducts/well). For antiserum developed against B[c]PhDE-1-DNA, 50% inhibition required 570 fmol B[c]PhDE-1-DNA adducts in wells coated with 100 fmol B[c]PhDE-1-DNA adducts. 7,12-Dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA and B[c]PhDE-2-DNA were also effective competitors: they caused 50% inhibition at 1900 and 1800 fmol adducts/well respectively. In contrast, benzo[a]pyrene-7,8 diol-9,10-epoxide-2-DNA gave no inhibition at the highest dose of competitor tested (4050 fmol adducts/well). Antisera from three rabbits immunized with B[c]PhDE-2-DNA demonstrated similar antigen specificities. The properties of these antisera differ from those reported previously for antibodies developed against benzo[a]pyrene-DNA in that they show selectivity for DNA modified by specific hydrocarbon diolepoxides, in one case for B[c]PhDE-2-DNA and in the other for B[c]PhDE-DNA or 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1 DNA. The specificity of these antisera will facilitate analysis of the modification of DNA by different polycyclic aromatic hydrocarbon diolepoxides. PMID- 1587006 TI - Inhibitory effects of diallyl sulfide on the metabolism and tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) in A/J mouse lung. AB - Diallyl sulfide (DAS), a component of garlic oil, has been shown to inhibit tumorigenesis by several chemical carcinogens. Our previous work demonstrated that DAS inhibited the metabolic activation of carcinogenic nitrosamines, including the tobacco-specific 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), in rat lung and nasal mucosa microsomes. In the present study, the effects of DAS on the tumorigenicity and the metabolism of NNK in A/J mouse lung were examined. Female A/J mice at 7 weeks of age were pretreated with DAS (200 mg/kg body wt in corn oil, p.o) daily for 3 days. Two hours after the final DAS treatment, the mice were either given a single dose of NNK (2 mg/mouse, i.p.) and kept for an additional 16 weeks for determining the production of pulmonary tumors, or were killed immediately so as to measure the microsomal activity in metabolizing NNK. In comparison to the vehicle control group, DAS pretreatment significantly decreased the incidence of NNK-induced lung tumors (37.9 versus 100%) and the tumor multiplicity (0.6 versus 7.2 tumors/mouse). In pulmonary metabolism of NNK, DAS pretreatment reduced the rates of formation of keto aldehyde, keto alcohol, NNAL-N-oxide, and NNK-N-oxide by 70-90%. In addition, the formation of NNK oxidative metabolites from NNK in the liver microsomes from DAS pretreated mice was remarkably reduced. DAS also inhibited the metabolism of NNK in mouse lung microsomes in vitro. These results demonstrate that DAS is an effective chemopreventive agent against NNK-induced lung tumorigenesis, probably by inhibiting the metabolic activation of NNK. PMID- 1587007 TI - Involvement of prostaglandin E2 in ornithine decarboxylase induction by a tumor promoting agent, 7-bromomethylbenz[a]anthracene, in mouse epidermis. AB - A single topical application of 7-bromomethyl-benz[a]anthracene (BrMBA; 200 nmol) to mouse skin induced epidermal ornithine decarboxylase (ODC) activity. A topical application of indomethacin (1.2 mumol), a cyclooxygenase inhibitor, 10 min before BrMBA application markedly inhibited BrMBA-caused ODC induction. Concurrent application of prostaglandin E2 (PGE2; 0.1-1.5 mumol) reversed the inhibitory effect of indomethacin. Without indomethacin, PGE2 suppressed BrMBA caused ODC induction. The results indicate that PGE2 has dual actions on the BrMBA-caused ODC induction, i.e. PGE2 plays an essential role in ODC induction caused by BrMBA, whereas exogenous PGE2 rather suppressed BrMBA-caused ODC induction. PMID- 1587008 TI - Metabolic activation of the food mutagens 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ) to DNA binding species in human mammary epithelial cells. AB - When incubated in suspension with the heterocyclic aromatic amine food mutagens 2 amino-3-methylimidazo [4,5-f]-quinoline (IQ) and 2-amino-3,4-dimethylimidazo[4,5 f]quinoline (MeIQ), human mammary epithelial cell aggregates were found, by 32P postlabelling analysis, to yield DNA that contained adducts. Analysis by HPLC of the 32P-labelled digests of mammary cell DNA indicated that in each case a major adduct peak corresponded to that produced in DNA in vitro by activated derivatives of the two compounds. The patterns of adducts obtained when DNA digests were separated by TLC on polyethyleneimine-cellulose plates were found to resemble those previously shown to be present in DNA of tissues of mice fed IQ or MeIQ. These results demonstrate the ability of human mammary epithelial cells to activate carcinogenic heterocyclic compounds known to be present in the human diet to DNA binding derivatives. PMID- 1587009 TI - Consumer views of health care: a comparison of hospital and home care. AB - A small interview study (n = 40) is described. Families were generally satisfied with their health care experience although they expressed a clear preference for home care as compared with hospitalization. A significant group of parents identified lack of information as a shortcoming of hospital care. PMID- 1587010 TI - Nightmares, life events and behaviour problems in preschool children. AB - A postal survey was carried out to identify nursery school children with frequent nightmares in an English city. Of the 22 children reported as suffering from frequent nightmares, 14 came from families who were willing to be interviewed further. A control group with no nightmares, matched for age and sex, was selected from the returns. The mothers of the children in the two groups were interviewed using the Preschool Behaviour Checklist and a life events scale. The results showed that neither life events nor behaviour problems were more prevalent in the frequent nightmares group. PMID- 1587011 TI - What do foster parents think of the natural parents? A comparative study. AB - By means of standardized case vignettes and rating scales, this study compared attitudes of short-term foster parents, professional social workers and parents in the general population respectively towards birth parents of abused children received into foster care. Significant differences arose between the foster parents and comparison groups on dimensions about issues relating to the desirability of foster care, restrictions on contact with birth parents and conditions under which the abused child might return to its family. Wide variation occurred both between individual foster parents and also in the degree of correspondence of views between the foster parents and each of the comparison groups on individual dimensions. Such an anomalous position, if unacknowledged, might affect outcomes of individual foster placements and hold implications for the recruitment, training and support of foster parents. PMID- 1587012 TI - Everyday and medical life choices: decision-making among 8- to 15-year-old school students. AB - How much do young patients expect to be involved in medical decisions affecting them? We are investigating this question during interviews with 8- to 15-year olds having orthopaedic surgery. Many youngsters taking part in our research project on consent to surgery are more than usually dependent on their parents. We wondered how their views would compare with those of their peers at school. This paper reports a schools survey carried out as a background to the research with young people in hospital. Students in seven schools answered questionnaires on choices about late-night television viewing, new friends, timing homework, seeing their family doctor and consenting to surgery. They were asked about agreement with their parents, how they negotiate disagreement, and when they think they were/will be old enough to make everyday and medical decisions without their parents' help. PMID- 1587013 TI - Chronic fatigue and immune dysfunction. PMID- 1587015 TI - The challenges of HIV nephropathy. PMID- 1587014 TI - Assessing new techniques in coronary angioplasty. AB - New devices for coronary intervention have been used in thousands of patients over the past several years. Although most such devices are still investigational, they hold promise in eliminating some of the hindrances to the broader, more successful use of conventional angioplasty. These new devices seem more effective than conventional angioplasty in treating eccentric or ulcerated lesions, ostial stenosis or stenosis of the LAD artery, disease in older saphenous vein grafts, restenotic lesions after prior intervention, and dissected vessels with actual or threatened abrupt closure. The difficulty facing each clinician is deciding which device to use under which circumstances in order to provide the safest, most durable, and most cost-effective treatment for the individual patient. Careful and critical analysis of the growing body of information regarding experience with these newer devices will be needed in order to accomplish this goal. PMID- 1587016 TI - Sleep in the patient with lung disease. AB - Normal sleep is associated with changes in respiration. The impact of sleep on patients with underlying lung disease may be significant depending on the severity of the underlying disease. Nocturnal oxygen desaturation may complicate the management of patients with chronic obstructive pulmonary disease, interstitial lung disease, and kyphoscoliosis. Nocturnal bronchospasm may develop in patients with asthma. The impact of sleep on these four disorders, as well as diagnostic and therapeutic considerations, are reviewed. PMID- 1587017 TI - Survivors of sudden cardiac death: a rational approach to evaluation and therapy of patients surviving ventricular fibrillation. AB - Survivors of out-of-hospital cardiac arrest that is not associated with acute myocardial infarction are at high risk for subsequent life-threatening ventricular tachyarrhythmias. A rational approach to evaluating the underlying disease processes and to formulating a specific treatment plan for these patients is presented. A protocol is suggested whereby existing cardiac conditions are appropriately treated and hemodynamic parameters are optimized. Myocardial ischemia is minimized with drugs or revascularization; this may suffice to prevent recurrence of sudden cardiac death in a small group of patients. For remaining patients at high risk of recurrence, the implantable cardioverter defibrillator is the therapy associated with the lowest rate of mortality. PMID- 1587019 TI - Catheter ablation for recurrent ventricular tachycardia. AB - A 78-year-old man had sustained ventricular tachycardia refractory to drug therapy. An antitachycardia pacemaker and a cardioverter-defibrillator were implanted. It was suspected that rate crossover was occurring between his sinus rhythm and his antitachycardia pacemaker detection rate. He also had frequent discharges from his implantable cardioverter-defibrillator. Because of these problems, he was considered a candidate for catheter ablation treatment of his ventricular tachycardia. The procedure was completed successfully and long-term follow-up has been uneventful. Catheter ablation is recommended as a treatment option for patients who have ventricular tachycardia that is refractory to drug therapy and combined-device therapy, and who have rate crossover. PMID- 1587018 TI - Indications for electrophysiologic study in patients with ventricular arrhythmias. AB - Electrophysiologic study provides valuable information in the management of patients with known or suspected ventricular tachyarrhythmias. It should be used when there is uncertainty about the origin of a wide QRS tachycardia. It is useful in evaluating heart disease patients with unexplained syncope and in stratifying prognosis and guiding therapy in patients with malignant ventricular arrhythmias. All patients being considered for treatment of ventricular tachyarrhythmias with an electrical device should undergo thorough electrophysiologic study. Electrophysiologic study is also indispensable in guiding ablative therapy in patients with drug-refractory malignant ventricular arrhythmias. PMID- 1587020 TI - Annular pancreas and intermittent duodenal obstruction in an alcoholic adult. AB - Annular pancreas is a congenital anomaly which, though present at birth, may cause few symptoms until adulthood. A case of annular pancreas with intermittent duodenal obstruction is described in a 49-year-old alcoholic man. Few other entities cause such obstruction. In similar cases, clinical suspicion of annular pancreas may lead to prompt diagnosis and treatment. PMID- 1587021 TI - Mental status changes in an immunocompromised patient. PMID- 1587022 TI - Endocarditis prophylaxis: the new guidelines. PMID- 1587023 TI - Globus sensation. PMID- 1587024 TI - Staging and prognostic factors in carcinoma of the base of the tongue. AB - During the period 1966-1985, 66 patients were submitted for curative treatment of a carcinoma of the base of the tongue in the Netherlands Cancer Institute. Treatment consisted of radiotherapy (59 patients), surgery and post-operative radiotherapy (4 patients) and surgery alone (3 patients). Patients were staged according to the UICC (1982) and UICC (1987)/AJCC (1988) criteria. Regrouping by the latter system caused enlargement of the N2-group and of stage IV. The crude 5 year survival was 22%, the 5-year tumour control was 36% and the locoregional control was 47%. The most important prognostic factors for the tumour-free interval are the T-category (P = 0.01) and stage grouping (UICC 1982) (P = 0.022). The same factors predict the locoregional control (P = 0.005 and 0.02 respectively). Crude survival is lower in smokers, and in patients in poor general condition (P = 0.04 and 0.007 respectively). PMID- 1587025 TI - Auditory function in patients infected with the human immunodeficiency virus. AB - A prospective study of auditory function in 18 HIV positive male patients at different CDC (Centres for Disease Control) stages was undertaken. One-third had abnormalities on either auditory evoked response testing or pure tone audiometry. No correlation was found between interwave latencies I-V, I-III, III-V and stage of disease determined either clinically or by T-cell subset. There was a weak correlation between pure tone averages at 1,2,4 kHz and 2,4,8 kHz and T-cell subset ratio in CDC Group IV disease (Rs = 0.56 and 0.57 respectively; P less than 0.05). Abnormalities of BSER were similar to those previously reported in HIV infection, and suggest isolated changes within the brain-stem. PMID- 1587026 TI - Endoscopic treatment of pharyngeal pouches: electrocoagulation vs carbon dioxide (CO2) laser. AB - Endoscopic treatment of a hypopharyngeal diverticulum was performed in 75 patients during the period 1976-1990. Initially electrocoagulation was used to divide the septum between the diverticulum and oesophagus. More recently, the CO2 laser combined with the operating microscope has been used. Although this has reduced the need for multiple endoscopic procedures compared to the electrocoagulation technique, this reduction was not statistically significant. In our follow-up group of patients, 49 (72.7%) were highly satisfied and 14 (19.6%) fairly satisfied. In this respect no significant differences between the electrocoagulation and laser group were found. Although we consider the use of the CO2 laser and operating microscope as a technical improvement of the former Dohlman procedure, further assessment needs to be done to evaluate whether laser therapy does offer an improvement in results. PMID- 1587027 TI - Child distress during hospitalization: implications for practice. AB - This paper investigates distress in 221 children admitted to a district general hospital for ENT surgery. Younger children (5 years and under) were rated by nurses as being most distressed, with girls more so than boys. Presence of a parent in hospital overnight is also found to be associated with higher levels of distress. It is suggested that preparation programmes designed to reduce distress should target younger children and that consideration be given to a preparation programme for parents. PMID- 1587029 TI - Photometrics: a new method of measuring the cross-sectional area of the subglottis. AB - A new endoscopic method of measuring the cross-sectional area of a subglottic stenosis is presented. The method was tested against existing techniques using a model. By standardizing the distance from the objective of the endoscope to the stenotic area we were able to measure the cross-sectional area using a graduated grid held against the video screen. This technique was then compared with the standard one of estimating the diameter of a stenosis from the external diameter of the bronchoscope which can be passed through the stenosis. The methods were found to be equally accurate in measuring the lumen diameter. However, when measuring the minimum cross-sectional area, three of five observers were significantly better (P less than 0.01) using the photometric method rather than the standard method (Wilcoxon's rank sum test for paired data). The photometric technique of measuring the cross-sectional area of the subglottis is easily performed, non-traumatic, and allows a visual record to be kept. PMID- 1587028 TI - The effect of adenoid and tonsil surgery on nasalance. AB - The change in nasalance following adenoidectomy, tonsillectomy and adenotonsillectomy was studied in 44 children. A subjective assessment of each child's naso-pharyngeal airway was made preoperatively based on a questionnaire completed by the parents. There was no significant change in the nasalance of children following adenoidectomy, but there was a significant increase in the nasalance following tonsillectomy (P = 0.02) and after adenotonsillectomy (P = 0.001). There was no relationship between the change in nasalance and the adenoid volume removed at operation. There was good agreement between the parental subjective assessment of the naso-pharyngeal airway and the preoperative nasalance score, with the best correlation in the adenoidectomy group (r = -0.8) and the adenotonsillectomy group (r = -0.7). Nasalance is more closely related to the size of the naso-pharyngeal airway than to the actual adenoid volume, and measurements of nasalance are of no benefit in predicting adenoid volume. Tonsillectomy had a significantly greater effect on nasalance than adenoidectomy, and adenotonsillectomy had the greatest effect. Further studies are needed to relate nasalance to the size of the naso-pharyngeal airway, but it appears to relate well to the subjective assessment of the airway and may be of use in patient selection for surgery. PMID- 1587030 TI - Hearing aids: family practitioner referral patterns. AB - This study aims to determine whether the implementation of a direct referral service in which family practitioners received feedback on the appropriateness of their patient selection had any impact on the referral pattern. Six months after the establishment of such a service to which general practitioners were requested to refer patients who satisfied the Hearing Aid Council and Therapist Technicians and Scientists in Audiology group criteria, 40 consecutive patients were analysed. 40 age matched controls referred concurrently to the routine ENT clinic for hearing aid provision were compared. In the 80 ears seen in each group, the number of perforations infected or otherwise were 2 and 7 respectively (P less than 0.01). Conductive hearing losses were more common in the control group (P less than 0.05). The degree of patient selection was higher than noted in the first 6 months of the service when the prevalence of perforations in the direct sample was 7%. It appears that the practice of selective referral has developed. PMID- 1587031 TI - A prospective study of otitis externa. AB - A prospective study of otitis externa in the district of South Bedfordshire was undertaken between October 1990 and January 1991. Patients were referred untreated by general practitioners; self-referred patients with external otitis were also included. A detailed history was taken, the severity of the condition assessed, aural toilet performed, bacteriology swabs taken and the patient treated according to department protocol. 48 patients were included in the study; a similar number of age and sex-matched controls without otitis externa were randomly selected from the ENT outpatient clinics for comparison. Regular swimming emerged as a significant factor in the aetiology of otitis externa. The commonest organism cultured was Pseudomonas aeruginosa and this accounted for the most severe cases seen. PMID- 1587032 TI - Ciliary beat frequency of nasal and middle ear mucosa in children with otitis media with effusion. AB - Impaired mucociliary function of respiratory tract mucosa is associated with secretory otitis media in some well recognized syndromes. Ciliary activity per se may now be assessed directly by determination of ciliary beat frequency by a photoelectric technique. 49 children with otitis media with effusion undergoing surgical treatment were studied. Middle ear mucosa and nasal epithelial cells were obtained by biopsy and cytological brushings respectively at the time of surgery (myringotomy +/- grommet insertion under general anaesthesia). From these samples mean nasal ciliary beat frequency was 11.0 Hz and mean middle ear ciliary beat frequency was 11.2 Hz. A positive correlation exists between mean ciliary beat frequency of nasal and middle ear samples from individual patients. A comparison of mean ciliary beat frequency between children who were effusion positive and effusion negative at the time of surgery revealed no statistically significant difference. In addition, no difference existed between those children with recurrent otitis media with effusion and newly presenting cases. No prima facie evidence exists of impaired ciliary function in this population of children with otitis media with effusion. PMID- 1587033 TI - Nasal packing after septoplasty. AB - A prospective study to compare 3 different types of nasal pack after septoplasty with or without a supplementary turbinectomy has been performed with respect to discomfort and complications caused by the packing and the short-term results evaluated 3 months after operation. Fingerstall packings gave less problems than either Merocel or hydrocortisone-terramycine gauze packs with ventilation tubes. They were easier to remove and were associated with less persistent secretion in the post-operative period. No definite advantage from the patient's point of view has been demonstrated by the use of tubes and nasal packing. An analysis of the nasal patency 3 months post-operatively by peak-flow index and acoustic rhinometry revealed no differences between groups. PMID- 1587034 TI - Control of neck nodes in squamous cell carcinoma of the head and neck by radiotherapy: prognostic factors. AB - 313 patients with cervical metastases from a squamous carcinoma of the head and neck treated with radiotherapy, were studied by means of a multivariant analysis in order to determine the prognostic factors for cure. These were: lymph node response to irradiation (P = 0.0000), size of node (P = 0.0000), radiotherapy dose (P = 0.0037), condition of the primary (controlled vs non-controlled) (P = 0.0015), recurrent cervical metastases post-surgery (P = 0.0286). PMID- 1587035 TI - Evaluation of nasal resistance data in active anterior rhinomanometry with special reference to clinical usefulness and test-retest analysis. AB - A systematic evaluation of the most common parameters used in active anterior rhinomanometry was made with artificial tube and cadaver models and patient recordings. The clinical suitability of the parameters was judged on their calculability, reproducibility and power to separate the recordings into meaningful degrees of patency. It was shown that resistance at 150 Pa was not calculable in 30% of the measurements because such a high pressure gradient was not achieved during quiet breathing. The power to separate the grades of obstruction was good with all the models but in the test-retest analysis, it was shown that the power to detect +/- 20% variation in repeated measurement in the same person with a decongested nose was not sufficient with the resistance at 150 ml/s and at radius 100. The coefficient of resistance W = P/V2 at peak flow and resistance at radius 200 showed good capability to separate the grades of obstruction, they are measurable in all recordings, their reproducibility is good and thus, they are recommended for clinical practice. PMID- 1587036 TI - Evaluation of active anterior and posterior rhinomanometry in normal subjects. AB - In this study active anterior (AAR) and active posterior (APR) rhinomanometry were performed by 100 normal subjects with a Mercury rhinomanometer according to the recommendations of the International Standardization Committee. There was no significant difference between total nasal airway resistance (Rna) values obtained with APR by direct measurement and those calculated from AAR. Mean total Rna was 0.31 Pa/cm3/s (range 0.13-0.84) at a reference pressure of 75 Pa. Measurements by AAR were more reproducible than those by APR, mean intrasubject coefficients of variation were 12 and 16% respectively. This reproducibility was similar to that of lower airways' resistance measurements. Rna values from this population did not conform to a normal Gaussian distribution. Rna was higher during expiration than inspiration and values were higher in women than in men. PMID- 1587037 TI - Routine nasopharyngeal biopsy in adult secretory otitis media. AB - This study was to determine whether routine examination under anaesthesia and nasopharyngeal biopsy in adults presenting with deafness due to secretory otitis media (SOM) is necessary for detection of nasopharyngeal malignancy. Two patient groups were studied. The first comprised 72 adults with SOM. Of these patients, 3 had nasopharyngeal tumours, 2 of whom also had cervical lymphadenopathy. The prevalence of malignancy in patients with SOM but no other suspicious signs was 1/72 (1.4%). The second group comprised 66 patients receiving treatment for nasopharyngeal neoplasms. In this group, 8 patients had SOM at presentation, 7 of whom had other features suspicious of malignancy. SOM as the sole presenting feature of nasopharyngeal malignancy was 1/66 (1.5%). EUA and biopsy of the nasopharynx is a cost effective investigation which continues to be indicated in adults presenting with deafness due to SOM. PMID- 1587038 TI - Otolaryngologic manifestations of phenytoin toxicity. AB - DPH may result in protean head and neck manifestations (Table 1). In some cases these effects are dose related and in others they appear to be idiosyncratic; some occur only at toxic levels (Table 2). Many of the conditions are reversible and withdrawal of DPH or re-establishment of therapeutic levels is the only treatment necessary. Failure to recognize this fact can result in expensive workups or, worse, in aggressive treatment, both of which are unnecessary. The otolaryngologist should therefore be aware of these conditions and consider them in the differential diagnosis. PMID- 1587039 TI - Iliopelvic lymphoscintigraphy as a predictor of early metastatic disease in patients with prostate carcinoma. AB - Fifty-one patients had iliopelvic lymphoscintigraphy (IPL) as part of the initial assessment of newly diagnosed prostate carcinoma over a 3-year period. Investigations other than IPL showed that all patients had disease confined to the prostate, and they received radiotherapy to the prostate and regional pelvic lymph nodes. Patients with complete absence of activity in an iliac chain on IPL were excluded from the analysis because that finding could have resulted from tumor replacement or a failed injection. Of the remaining 41 patients, 12 had abnormal scintigrams, and 6 (50%) had recurrence within a mean 15-month follow-up period. Of 29 patients with normal scintigrams, 26 (90%) remain disease free over an average 27-month follow-up period. PMID- 1587040 TI - Differential diagnosis of idiopathic fibrosis from malignant lymphadenopathy with PET and F-18 fluorodeoxyglucose. AB - Idiopathic fibrosis and malignant lymphoma were studied with positron emission tomography (PET) using 2-deoxy-2-[F-18]fluoro-D-glucose (F-18DG). Cases of retroperitoneal fibrosis and sclerosing peritonitis showed low F-18DG uptake with the mass/muscle radioactivity (M/M) ratio 2.0 and 1.9, respectively. A case of para-aortic adenopathy from malignant lymphoma showed high F-18DG uptake with the M/M ratio 9.4. F-18DG PET study may be useful for the differential diagnosis of idiopathic fibrosis and malignant lymphadenopathy. PMID- 1587041 TI - In-111 labeled leukocyte imaging in a case of pseudogout. AB - In-111 labeled leukocyte scintigraphy was performed on a 90-year-old woman who had a fever and left lower extremity pain for 3 days. Leukocyte images demonstrated abnormal activity in the left knee and ankle. Aspiration of the left knee joint yielded cloudy yellow fluid with a leukocyte count of 30,000 per mm3 (75% polymorphonuclear leukocytes, 1% lymphocytes, and 24% monocytes). Cultures of the aspirate were reported as no growth. Microscopic examination of the aspirate revealed the presence of rod-shaped crystals of calcium pyrophosphate dihydrate, confirming the diagnosis of calcium pyrophosphate deposition disease, also known as pseudogout. The acute arthritis of pseudogout stimulates an intense leukocyte response; therefore, labeled leukocyte images performed on patients suspected of having this condition must be interpreted cautiously because scintigraphically it may not be possible to distinguish pseudogout from septic arthritis. PMID- 1587042 TI - Uptake of In-111 labeled leukocytes by lymphocele. A cause of false-positive vascular graft infection. AB - In-111 labeled leukocyte scintigraphy is a sensitive test for the diagnosis of prosthetic vascular graft infections. However, several causes of false-positive results have been reported. The authors describe a case of uninfected lymphocele around a synthetic vascular graft in a patient who showed an infected graft on In 111 labeled leukocyte scintigraphy. PMID- 1587043 TI - Effect of dilantin on myocardial uptake of Tl-201 thallous chloride. A case report. AB - Dilantin has been reported to decrease myocardial uptake of Tl-201 thallous chloride by as much as 38.8% in rats. To date, no studies have been done in humans to document the effect of dilantin on the myocardial uptake of thallium or its effect clinically on the interpretation of images obtained while on dilantin. The authors report a case in which simultaneous exercise echocardiogram and Tl 201 myocardial scintigraphy and serial Tl-201 myocardial scintigraphy were performed but revealed no adverse effect on image quality or interpretation. PMID- 1587044 TI - Visualization of brainstem perfusion using a high spatial resolution SPECT system. AB - The authors explored the high spatial resolution of a three-head rotating SPECT system, equipped with lead super-fine fanbeam collimator. The brainstem was high lighted in a three-dimensional reconstruction, showing perfusion small structures such as mesencephalon, pons, and medulla oblongata. The visualization of brainstem perfusion sets new landmarks in functional neuroimaging and, moreover, was obtained with a commercially available three-head SPECT system. PMID- 1587045 TI - Ga-67 scintigraphy and computed tomography in the diagnosis of pneumocystis carinii pneumonia in patients with AIDS. A prospective comparison. AB - A prospective evaluation of Ga-67 scintigraphy and transmission computed tomography was performed in 70 consecutive patients with AIDS who were suspected of having Pneumocystis carinii pneumonia. Studies were evaluated independently by two observers. Receiver operating characteristic curves were plotted. Although scintigraphy had a higher true-positive ratio at any false-positive ratio, statistically the areas under the two receiver operating characteristic curves were not significantly different. However, at an FP rate of 15% to 20% (one in the clinically reasonable range), the sensitivity for scintigraphy was 0.84 and for CT 0.80; corresponding specificities were 0.82 and 0.64, respectively, for the two modalities. It seems from these data that gallium imaging is probably superior to CT in detecting P. carinii pneumonia in this group of patients. PMID- 1587047 TI - Radionuclide imaging of relapsing polychondritis. PMID- 1587046 TI - Prediction of muscle viability after electrical burn necrosis. AB - In this preliminary study, Tc-99m MIBI, a muscle perfusion agent, was used to assess the viability of tissues in two patients with extensive high-tension electrical burns. This proved to be an easy and definitive diagnostic procedure and a practical solution to determining the level of amputation before surgery. PMID- 1587048 TI - The case of the flip-flop clot. PMID- 1587049 TI - Scintigraphic demonstration of sequestered nodular goiter. A lateral aberrant thyroid rest. PMID- 1587050 TI - In-111 leukocyte imaging in disseminated mycobacterium avium-intracellulare infection. PMID- 1587051 TI - Acute transient myocarditis. Evaluation by gallium imaging. PMID- 1587052 TI - Pseudobiliary leak. PMID- 1587053 TI - Flare response in Ewing's sarcoma. PMID- 1587054 TI - Controversies in determination of epoetin (recombinant human erythropoietin) dosages. PMID- 1587055 TI - Clinical pharmacokinetics of calcium antagonists. An update. AB - The calcium antagonists are valuable and widely used agents in the management of essential hypertension and angina. There is an increasing number of new agents to add to the 3 prototype substances nifedipine, diltiazem and verapamil. These new agents are dihydropyridines structurally related to nifedipine. However, they tend to have longer elimination half-lives (t 1/2 beta) and may be suitable for twice-daily administration. Amlodipine is an exception with a t 1/2 beta in excess of 30h. Apart from elimination rates, however, the pharmacokinetic characteristics of the newer agents have a notable tendency to resemble those of the established agents. They are highly cleared drugs, are relatively highly protein bound. As they are subject to significant first-pass metabolism, old age and hepatic impairment will increase their plasma concentrations due to a reduced first-pass effect. Renal impairment does little to their pharmacokinetics since the fraction eliminated unchanged by the kidney is small. For most agents, plasma concentration-response relationships have been described. Interesting areas for further research include chronopharmacokinetics, stereoselective pharmacokinetics and lipid solubility. Drugs affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. Some of the newer calcium antagonists will, like verapamil, increase plasma digoxin concentrations. Verapamil and diltiazem decrease phenazone (antipyrine) metabolism and therefore tend to decrease the metabolism of other drugs. PMID- 1587056 TI - The use of vaccines in renal failure. AB - Renal insufficiency is characterised by impaired host defences, which are compromised further by each of the 3 modes of renal replacement--haemodialysis, continuous ambulatory peritoneal dialysis (CAPD) and renal transplantation. Reduced renal clearance of unknown toxins, possible development of nutritional deficiencies and administration of immunosuppressive medications lead to aberrant immune regulation early in the course of renal failure. This results subsequently in increased frequency and severity of infection. Vaccination plays an important role in attenuating this infection risk, but impaired cell-mediated and humoral immunity contraindicates the use of live vaccines and engenders suboptimal and short-lived antibody responses to inactivated vaccines. Reinforced vaccination schedules, increased vaccine dosage and concomitantly administered adjuvant immunomodulators have variably improved the defective antibody responses to certain vaccines. Immunisation against hepatitis B virus has resulted in a significant decrease in prevalence and incidence of this infection in haemodialysis units. Similarly, the inoculation of influenza vaccine in patients with uraemia and of polyvalent pneumococcal vaccine in special risk circumstances has been recommended because of perceived reductions in morbidity and mortality from infection with these agents. Cytomegalovirus (CMV) vaccine may attenuate CMV disease severity in recipients of renal allografts. Staphylococcus aureus vaccine, on the other hand, is ineffective in preventing peritonitis or exit site infections in patients receiving CAPD. Other killed vaccines have not been comprehensively studied, but generally have the same indications for use as in normal individuals. However, the protection that these vaccines afford may be either inadequate or transient, so that other infection control strategies should be simultaneously implemented. PMID- 1587059 TI - Phenobarbital pharmacokinetics in obesity. A case report. AB - A morbidly obese woman [190 kg total bodyweight (TBW)] was admitted to hospital with a rapidly progressing wound infection. Over the next 2 weeks the patient developed congestive heart failure, acute renal failure, septic shock and multiple seizure episodes. Intravenous phenobarbital was added to phenytoin therapy to achieve seizure control. A total loading dose of phenobarbital 3700 mg (19.5 mg/kg TBW) was administered in 3 divided doses. The initial dose of 1100 mg resulted in a serum phenobarbital concentration of 6.3 mg/L 5h postinfusion, a second 1100 mg dose increased the concentration to 13.1 mg/L 1h postinfusion and a final dose of 1500 mg resulted in a 22.5 mg/L concentration at the end of the infusion. A phenobarbital maintenance regimen of 120 mg every 12h was then started. Peak serum concentrations of 19.8 and 17.8 mg/L were measured. All of the available serum phenobarbital concentrations and dosage amounts were fitted with least-squares nonlinear regression analysis to a 1-compartment model. An apparent volume of distribution (Vd) of 154.9L (0.82 L/kg TBW), total body clearance (CL) of 29 ml/min (1.74 L/h) and elimination half-life of 61h were determined. Our case report suggests that the dose of intravenous phenobarbital should be calculated using TBW. Additional studies are needed to precisely define the appropriate dosage weight, serum concentrations and clinical efficacy associated with intravenous phenobarbital in morbidly obese patients. PMID- 1587060 TI - The formulary: an educational tool for clinical pharmacology. PMID- 1587058 TI - Pharmacokinetics of quinidine in male patients. A population analysis. AB - Quinidine pharmacokinetic behaviour was evaluated in 139 adult hospitalised men receiving oral quinidine therapy. A total of 391 serum quinidine concentrations were measured by enzyme immunoassay for routine clinical purposes. The NONMEM programme was used to examine the relationship between quinidine pharmacokinetics and several potential covariates. A 1-compartment open model with first-order absorption and elimination was assumed. The mean apparent volume of distribution (Vd) was about 230L. When measured, alpha 1-acid glycoprotein (AAG) levels were not included in the analysis. Oral quinidine clearance (CL) decreased with age, severe congestive heart failure and renal disease, and increased in patients with a history of alcohol abuse. The interpatient variability in CL and the intrapatient residual variability expressed as coefficients of variation (CV) were 28 and 31%, respectively. When AAG values were incorporated into the analysis, the only important covariates of CL were the AAG measurements and the presence of renal dysfunction as indicated by a calculated creatinine clearance of less than 50 ml/min (3 L/h). The interpatient variability in CL and the residual intrapatient CVs decreased to approximately 24 and 26%, respectively. Improvement of the CL model by inclusion of measured AAG strongly suggests that quinidine elimination is dependent on the free concentration of drug in plasma and supports the use of free serum quinidine concentrations when evaluating and monitoring quinidine therapy. PMID- 1587061 TI - Age and propranolol stereoselective disposition in humans. AB - The apparent oral clearance of S(-)- and R(+)-propranolol as a function of age was evaluated in 53 healthy male volunteers (age range, 21 to 84 years) after a single 40 mg oral dose of the racemic mixture. No significant age-associated change in the total (bound plus unbound) and unbound S(-) and R(+) apparent oral clearance was observed (p greater than 0.05). Stereoselectivity in apparent oral clearance (both total and unbound) remained unaffected by advancing age (p greater than 0.05). The relationship between age and propranolol enantiomer plasma protein binding was also evaluated in 70 subjects, 53 of whom were from this study (age range, 21 to 89 years). Plasma free fractions for S(-)- and R(+) propranolol were unchanged with increasing age (p greater than 0.05), even though the binding was stereoselective (plasma free fractions for R(+) greater than plasma free fractions for S(-); p less than 0.05). The findings from this relatively large and extensive study indicate that age does not influence the stereoselective disposition of propranolol. PMID- 1587057 TI - Bayesian parameter estimation and population pharmacokinetics. AB - The widespread application of Bayesian parameter estimation in the area of therapeutic drug monitoring (TDM) has prompted the need for well conducted population studies to obtain relevant prior pharmacokinetic parameter estimates. In many cases the population has consisted of a relatively small number of subjects. This may be unavoidable for drugs used in cancer chemotherapy or in small, specific populations of patients. In contrast, information about drugs which are used extensively, such as the aminoglycosides, can be obtained by population studies which involve a large number of individuals. Indeed, this technique has proved particularly useful for determining parameter estimates which can be employed in neonatal TDM. Bayesian parameter estimation has been most frequently used for drugs with narrow therapeutic ranges such as the aminoglycosides, cyclosporin, digoxin, anticonvulsants (especially phenytoin), lithium and theophylline. However, the technique has now been extended to cytotoxic drugs, Factor VIII and warfarin. Bayesian methods have also been used to limit the number of samples required in more conventional pharmacokinetic studies with new drugs. Further advances in the use of these methods are likely to include measures of drug response and toxicity requiring population studies which also include relevant pharmacodynamic information. PMID- 1587062 TI - Racial differences in propranolol pharmacokinetics. AB - Racial differences in the antihypertensive response to propranolol are well documented. This study was conducted to determine whether differences between black subjects and white subjects in propranolol enantiomer pharmacokinetics and protein binding exist that may contribute to the response differences. Twenty-six healthy men (13 black and 13 white subjects) took 80 mg propranolol orally three times daily for 16 doses. Serum samples were collected for 12 hours after the last dose for analysis by chiral HPLC. Protein binding was determined by equilibrium dialysis. Area under the serum concentration-time curve (AUC) for both propranolol enantiomers was lower in black subjects than in white subjects (e.g., l-propranolol AUC: 292 +/- 100 versus 394 +/- 121 ng.hr/ml, p less than 0.05) and apparent oral clearance was higher in black subjects than in white subjects (e.g., l-propranolol apparent oral clearance: 27.6 +/- 8.2 versus 20.6 +/- 7.0 ml/min/kg, p less than 0.05). Fraction unbound and unbound AUC were not statistically different between black subjects and white subjects for either enantiomer, although the lack of statistical significance may have been attributable to the small sample size. In summary, racial differences in unbound l-propranolol concentration probably do not explain the clinically observed differences in response to propranolol. However, the racial differences in apparent oral clearance suggest there may be racial differences in hepatic metabolism of propranolol. PMID- 1587063 TI - Significant weight reduction in obese subjects enhances carbamazepine elimination. AB - Single-dose (200 mg) carbamazepine pharmacokinetics was evaluated in six obese, otherwise healthy subjects, before and after a mean +/- SEM weight reduction of 30.0 +/- 5.0 kg over 11.3 +/- 1.2 months. After weight loss the mean +/- SEM plasma elimination half-life (t1/2) of carbamazepine was significantly shortened (60.3 +/- 3.1 versus 30.8 +/- 3.3 hours, p less than 0.01) and the total plasma clearance (CL) increased (20.4 +/- 1.8 versus 31.6 +/- 5.0 ml/min, p less than 0.05). The apparent volume of distribution (Varea) decreased (106.2 +/- 9.9 versus 77.7 +/- 4.5 L, p less than 0.01); however, no difference was evident when carbamazepine Varea was corrected for body weight. In addition, weight loss coincided in all participants with a complete sonographic disappearance of the initial fatty liver infiltration noted on enrollment. In conclusion, obesity associated with fatty liver presents an enlarged carbamazepine Varea, prolonged carbamazepine t1/2, and reduced carbamazepine CL. Whenever carbamazepine is initiated in obese subjects, steady-state concentrations should be expected only after twice the time required to achieve steady state in lean subjects. Thus carbamazepine maintenance dose should be reduced, dose interval prolonged, and monitoring of carbamazepine plasma levels provided. PMID- 1587064 TI - Relation between chloroguanide bioactivation to cycloguanil and the genetically determined metabolism of mephenytoin in humans. AB - It has been suggested recently that the bioactivation of chloroguanide hydrochloride (proguanil) to its active antimalarial metabolite cycloguanil cosegregates with the genetically determined polymorphism of mephenytoin hydroxylation. We determined the chloroguanide to cycloguanil ratio in urine after oral administration of a single dose of 200 mg proguanil either alone or together with 100 mg racemic mephenytoin or 40 mg dextromethorphan in a randomized crossover study performed in 24 healthy subjects. The mephenytoin hydroxylation index was also determined after administration of 100 mg racemic mephenytoin either alone or together with 200 mg proguanil. Two subjects were poor metabolizers and one subject was an intermediate metabolizer of mephenytoin. These three subjects had chloroguanide to cycloguanil ratios of more than 50. The 21 subjects with the extensive metabolizer phenotype for mephenytoin hydroxylation had chloroguanide to cycloguanil ratios of less than 10. The chloroguanide to cycloguanil ratio was not significantly altered by mephenytoin or dextromethorphan coadministration. The trend toward a correlation between chloroguanide/cycloguanil ratio and log mephenytoin hydroxylation index did not reach statistical significance. Inclusion of the dextromethorphan metabolic ratio into the model did not improve the relationship. These findings confirm that the bioactivation of chloroguanide to cycloguanil cosegregates with the genetically determined activity of the CYP2C family. However, the chloroguanide to cycloguanil ratio and the mephenytoin hydroxylation index do not similarly reflect the variable activity of CYP2C. PMID- 1587065 TI - Drug concentration response relationships in normal volunteers after oral administration of losartan, an angiotensin II receptor antagonist. AB - The aim of this study was to investigate the relationships between plasma concentrations of losartan, an orally active angiotensin II inhibitor, its active metabolite EXP3174, and angiotensin II blockade. Six healthy subjects received single oral doses of 40, 80, or 120 mg losartan and placebo at 1-week intervals in a crossover study. Angiotensin II blockade was assessed by the blood pressure response to exogenous angiotensin II before and after losartan administration. EXP3174 reached higher plasma concentrations and was eliminated more slowly than its parent compound; its levels paralleled the profile of angiotensin II blockade closer than losartan. Inhibition of the pressure response was dose dependent. The Hill-shaped relationship between response and EXP3174 concentration (or time integrated variables) approached a plateau with 80 mg. The dose-dependent increase in plasma renin and angiotensin II exhibited a considerable individual scatter. We conclude that losartan produces a dose-dependent, effective angiotensin II blockade that is largely determined by the active metabolite EXP3174. PMID- 1587066 TI - Sulfamethoxazole is metabolized to the hydroxylamine in humans. AB - The oxidation of sulfamethoxazole to its hydroxylamine metabolite was investigated in vitro with human liver microsomes and in vivo by detection in the urine. Sulfamethoxazole was oxidized to the hydroxylamine in an NADPH-dependent process by liver microsomes prepared from two human livers. Three healthy volunteers ingested 1000 mg sulfamethoxazole, and urine was collected for 24 hours. Sulfamethoxazole hydroxylamine constituted 3.1% +/- 0.7% of the drug excreted in the urine in 24 hours. Fifty-four percent of the ingested dose was excreted during this same time period. We conclude that sulfamethoxazole hydroxylamine is an authentic in vivo metabolite in humans, probably formed predominantly by cytochrome P450 in the liver. It could be responsible for mediation of sulfonamide adverse reactions, particularly hypersensitivity reactions. PMID- 1587067 TI - Exercise alters the pharmacokinetics of midazolam. AB - Six healthy volunteers received 15 mg midazolam, 50 mg ephedrine, or placebo orally before a 50-minute aerobic treadmill exercise and in a control session. Plasma drug concentrations for pharmacokinetic calculations were estimated from samples drawn up to 24 hours after drug intake. Heart rate, blood pressure, critical flicker fusion test, Maddox wing test, and visual analog scales relating to mood and feelings of tiredness were included in the sessions as pharmacodynamic measures. These tests were made at 35, 55, and 75 minutes and at 2, 2 1/2, 3 1/2, and 5 hours after drug intake. Exercise impaired the absorption of midazolam and counteracted the midazolam-induced decrement in flicker fusion threshold. Whether the effect on flicker fusion was caused mainly by the pharmacokinetic changes or by a general alerting effect of exercise cannot be verified by this experiment. The kinetics of ephedrine was not affected by exercise, but exercise enhanced the tachycardic response to ephedrine and abolished its pressor effect. PMID- 1587068 TI - Alprazolam in end-stage renal disease. II. Pharmacodynamics. AB - The sensitivity to the psychomotor and memory effects of alprazolam was evaluated in 12 normal subjects and 12 dialysis patients (seven patients receiving hemodialysis and five patients receiving continuous ambulatory peritoneal dialysis). Subjects received a single oral dose of 0.5 mg alprazolam, 2 mg alprazolam, and placebo in a double-blind, placebo-controlled, balanced, three way crossover study with a Latin square design. After administration of the test drug, blood was obtained for alprazolam concentration and protein-binding determinations, and psychomotor performance, memory, and sedation were assessed. The maximum psychomotor impairment corrected for free alprazolam concentration was 5.0%, 8.2%, and 10.1% per nanogram per milliliter in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively (p less than 0.01), after administration of 2 mg alprazolam. Free alprazolam concentrations at which 50% of maximum effect is elicited for psychomotor impairment were 10, 7.40, and 5.31 ng/ml in normal subjects, patients receiving hemodialysis, and patients receiving continuous ambulatory peritoneal dialysis, respectively. The maximum memory impairment corrected for the maximum free alprazolam concentration was 4.4%, 7.2%, and 8.9% per nanogram per milliliter, respectively (p less than 0.09), after administration of 2 mg alprazolam. Thus our group of patients receiving dialysis showed enhanced sensitivity to some psychomotor and memory effects of alprazolam. PMID- 1587069 TI - Treatment of paroxysmal supraventricular tachycardia with oral diltiazem. AB - Symptomatic paroxysmal supraventricular tachycardia is a troubling arrhythmia for many patients. To test the efficacy of oral diltiazem to reduce symptomatic recurrences of paroxysmal supraventricular tachycardia, we enrolled 17 patients in a double-blind, placebo-controlled crossover study. Sixteen of 17 patients completed a dose-ranging phase and were entered into the randomized phase. Although the time to first recurrence of tachycardia was slightly longer when patients took diltiazem, the difference was not significant (p = 0.15). The hazard ratio of the time to first recurrence on placebo compared with oral diltiazem was 2.7 (95% confidence interval, 0.8 to 9.1). Of the patients who had a recurrence of tachycardia in both treatment periods, the median reduction in heart rate in patients receiving diltiazem was 20 beats/min. (p less than 0.01; 95% confidence interval, 6 to 42). PMID- 1587070 TI - Albuterol and deaths from asthma in New Zealand from 1969 to 1976: a case-control study. AB - It has been suggested that the association between inhaled fenoterol and deaths from asthma in New Zealand occurred because patients with unstable asthma were switched to fenoterol after its introduction in 1976. If so, a similar pattern might also have occurred after the introduction of albuterol (salbumatol) in 1969. This hypothesis has been investigated in a case-control study of 17 deaths from asthma during the period from 1969 to 1976 in patients whose ages ranged from 5 to 45 years; as in a previous study in New Zealand, two control groups were used. The inhaled albuterol odds ratio was 0.88 (95% confidence interval, 0.29 to 2.62) using control group A and 1.40 (95% confidence interval, 0.48 to 4.09) using control group B. The major problem with this study is the very small number of cases, but the findings nevertheless indicate that albuterol was not associated with deaths from asthma after its introduction. PMID- 1587071 TI - Possible interaction between cyclosporine and josamycin: a description of three cases. PMID- 1587072 TI - Long-term weight control study. I (weeks 0 to 34). The enhancement of behavior modification, caloric restriction, and exercise by fenfluramine plus phentermine versus placebo. AB - To investigate the value of anorexiant medications as an adjunct to other forms of weight control therapy, we studied 121 people in a 34-week, double-blind clinical trial of 60 mg extended-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise. Participants weighed 130% to 180% (154% +/- 1.2%, mean +/- SEM) of ideal body weight (1983 Metropolitan Life tables) and were in good health. By week 34, participants receiving active medication lost an average of 14.2 +/- 0.9 kg, or 15.9% +/- 0.9% of initial weight (n = 58), versus a loss of 4.6 +/- 0.8 kg or 4.9% +/- 0.9% of initial weight by subjects taking placebo (n = 54; p less than 0.001). On visual analog scales, participants rated fenfluramine plus phentermine as more helpful than placebo (50.3 +/- 0.5 versus 20.3 +/- 0.3) and not bothersome (fenfluramine plus phentermine, 17.4 +/- 0.3 versus 13.5 +/- 0.2). Blood pressure decreased and pulse remained unchanged in both groups. Dry mouth was the most common adverse effect in subjects receiving fenfluramine plus phentermine; all adverse effects decreased after 4 weeks. Only nine participants left the study in the first 34 weeks. Two subjects from each group left the study as a result of adverse effects. Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise aided weight loss and continued to be efficacious for 34 weeks. PMID- 1587073 TI - Long-term weight control study. II (weeks 34 to 104). An open-label study of continuous fenfluramine plus phentermine versus targeted intermittent medication as adjuncts to behavior modification, caloric restriction, and exercise. AB - Between weeks 34 and 104, we explored different schema for administering fenfluramine plus phentermine in open-label fashion. At week 34, the original placebo group participants began taking fenfluramine plus phentermine (placebo-to active group). Those receiving fenfluramine plus phentermine between weeks 6 and 34 either continued to receive medication or began targeted intermittent therapy. Participants who did not lose 10% of initial weight received an augmented dose (60 mg fenfluramine plus 30 mg phentermine. The placebo-to-active group lost an additional 9.1 +/- 0.8 kg (mean +/- SEM) in the period from week 34 to week 60. At week 60, they were assigned to either continue medication, intermittent therapy, or augmented therapy. More than 68% (83) of the original participants completed up to study week 104. At that point, overall weight loss was 10.8 +/- 0.7 kg (11.6 +/- 0.8% of initial weight); participants who continued to receive fenfluramine plus phentermine lost 11.6 +/- 0.8 kg, participants receiving intermittent therapy lost 11.6 +/- 1.3 kg, and participants receiving augmented therapy lost 6.5 +/- 1.5 kg. Although 41% of the participants complained of dry mouth, neither serious adverse effects nor evidence of medication abuse appeared. There were 29 dropouts in the period from weeks 34 to 104. Sixteen of those were related to medication (adverse effects, lack of efficacy, and fear of medication). Overall, fenfluramine plus phentermine used in conjunction with behavior modification, caloric restriction, and exercise continued to be efficacious for up to 2 years. PMID- 1587074 TI - Long-term weight control study. III (weeks 104 to 156). An open-label study of dose adjustment of fenfluramine and phentermine. AB - Between weeks 104 and 156 we attempted to optimize response by adjusting the doses of fenfluramine and phentermine. Dosing changes were based on an algorithm that aimed to achieve 120% of ideal body weight (IBW) while minimizing adverse effects. The dose groups were as follows: stage I, 30 mg fenfluramine plus 15 mg phentermine in the morning; stage II--continuous or targeted intermittent, 60 mg fenfluramine plus 15 mg phentermine in the morning; stage III, 60 mg fenfluramine plus 30 mg phentermine in the morning; stage IV, 60 mg fenfluramine plus 30 mg phentermine in the morning and 30 mg fenfluramine in the evening; and stage V, 60 mg fenfluramine plus 30 mg phentermine in the morning and 60 mg fenfluramine in the evening. Seventy-seven participants began this segment of the study and 59 completed to week 156. Completers of this segment of the study gained an average of 2.7 +/- 0.5 kg between weeks 104 and 156 but remained 9.4 +/- 0.8 kg (10.5%) below baseline. On average, weight loss from baseline by group was as follows: for stage I (n = 2), 14.1 +/- 6.8 kg; for stage II continuous (n = 14), 10.9 +/- 0.7 kg; for stage II targeted intermittent (n = 7), 8.8 +/- 2.4 kg; for stage III (n = 9), 7.7 +/- 2.6 kg; for stage IV (n = 8), 10.5 +/- 2.6 kg; and for stage V (n = 19), 8.4 +/- 2.4 kg. Upward dose adjustment (n = 36) resulted in further weight loss in 11 and no gain in six participants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587075 TI - Long-term weight control study. IV (weeks 156 to 190). The second double-blind phase. AB - To assess continued efficacy of anorexiants after 3 years of use, 52 participants (43% of those starting) entered a second double-blind trial to compare 60 mg sustained-release fenfluramine plus 15 mg phentermine resin versus placebo added to behavior modification, caloric restriction, and exercise. Although participants in both the active medication and placebo groups gained weight, participants receiving fenfluramine plus phentermine (n = 27) gained significantly (p less than 0.01) less (4.4 +/- 0.5 kg or 5.3% +/- 0.5% of initial weight) than participants receiving placebo (n = 24) (6.9 +/- 0.8 kg or 8.5% +/- 1.1% of initial weight). At week 190, both groups were still below their initial weight (fenfluramine plus phentermine group, 5.0 +/- 1.4 kg; placebo group, 2.1 +/- 1.2 kg; p less than 0.01). Overall, 12 participants (23.5% of those still in the study) were greater than or equal to 10% below initial weight. One participant dropped out during this phase because of personal reasons and loss of medication efficacy. During the 30 weeks, participants receiving fenfluramine plus phentermine had 26 moderate or severe complaints versus eight participants receiving placebo. Fenfluramine plus phentermine provided better appetite control and only slightly more bother. Analysis of participant response in this phase by treatment assignment in the first double-blind phase (weeks 6 to 34) indicated that initial receipt of medication did not have negative learning effects. Eleven participants receiving active medication between weeks 6 and 34 and receiving placebo between weeks 160 to 190 gained 5.1 +/- 1.0 kg. In contrast, 13 participants originally taking placebo gained 8.3 +/- 9 kg in this second double blind phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587076 TI - Long-term weight control study. V (weeks 190 to 210). Follow-up of participants after cessation of medication. AB - Participants who completed up to week 190 in the long-term weight control study were monitored after cessation of medication between weeks 190 and 210. Caloric restriction, behavior modification sessions, exercise reinforcement, and physician visits continued. We assessed whether or not participants had reset their weight control mechanisms and compared the effect of stopping medication under open-label conditions (weeks 190 to 210) with the results of stopping anorexiants under double-blind conditions (weeks 160 to 190). At week 210, participants were, on average, 1.4 +/- 1.0 kg (mean +/- SEM, 1.5% +/- 1.1%) below their weights at baseline (week 0). Of the 48 participants who remained in the study, 13 were still 5% or more and seven were 10% or more below their initial weights. On average, participants gained 2.7 +/- 0.5 kg (3.2%) in the period from weeks 190 to 210. Those who had been taking medication in the period from weeks 160 to 190 gained weight at a somewhat faster rate than those who had been taking placebo. However, participants who had transferred from fenfluramine plus phentermine to no medication in this phase gained at a slower rate than participants who had changed from fenfluramine plus phentermine to placebo under double-blind conditions at week 160 (0.195 kg per week versus 0.277 kg per week). The findings indicate that participants had difficulty maintaining weight loss without anorexiant medications. Despite long periods of time at weights much lower than baseline, permanent resetting of weight control mechanisms could not be shown for most participants. PMID- 1587077 TI - Long-term weight control study. VI. Individual participant response patterns. AB - We analyzed the individual response patterns of all 121 participants who entered the study. Fifty-one participants completed up to week 190. In 26 completers, the response pattern consisted of an initial beneficial effect (greater than or equal to 6 months of weight loss greater than or equal to 10% from baseline) and later success (weight loss of greater than or equal to 10% from baseline at week 160). These successful participants had lost 14.1 +/- 1.0 kg (mean +/- SEM); 15.9% +/- 0.9% of initial weight) at week 160 and 8.1 +/- 1.2 kg (9.1% +/- 1.3% of initial weight) at week 190. A second pattern observed in 16 completers consisted of initial benefit and later partial success (loss of 0.1% to 9.9% at week 160). Other response patterns observed in completers included showing initial benefit only (n = 3) and no success (n = 6). Seventy of the 121 participants left the study before week 190. There were 22 "dropout successes" who had consistent weight loss for 1 year or more and were greater than or equal to 10% below their initial weights at time of dropout. Fifteen "dropouts with initial benefit" stayed in the study for greater than or equal to 1 year with initial benefit (weight loss greater than or equal to 10% from baseline maintained for greater than or equal to 6 months). Medication-related reasons accounted for only 10 of the 37 dropouts in the group with initial or later benefit. Minimal benefit was seen in 17 dropouts. Another 16 were in the study less than 1 year. Analysis of individual participant responses made some other generalizations possible. Participants receiving continuous medication lost more weight and had fewer adverse effects than those receiving targeted intermittent medication. Upward dose adjustment appeared to help 24 participants achieve the criteria for late or partial success. Analyses of individual participant responses can suggest ways to optimize anorectic medication use for individual patients. PMID- 1587078 TI - Long-term weight control study. VII (weeks 0 to 210). Serum lipid changes. AB - We analyzed serum total cholesterol, triglycerides, and lipoprotein profile changes occurring in the participants (N = 121) through 210 weeks of the study. On average, baseline lipid levels were within normal limits. The most consistent changes occurred in the high-density lipoprotein cholesterol (HDL-C), serum total cholesterol/HDL-C ratios, and triglyceride levels. HDL-C increased significantly (p less than 0.01), compared with baseline, by 10% at week 34, 15% at week 54, 19% at week 104, and 27% at week 139. At week 210, 20 weeks after treatment had ended, HDL-C was 15% higher than baseline. At weeks 34, 54, 104, and 139, the serum total cholesterol/HDL-C ratio was significantly decreased, compared with baseline, by 9%, 19%, 17%, and 25%, respectively. At week 210, serum total cholesterol/HDL-C ratio was 8% less than week 0. Compared with baseline, triglyceride levels decreased significantly by 21%, 31%, 29%, and 29% at weeks 34, 54, 104, and 139, respectively. At week 210, triglyceride levels were 16% below baseline. Total cholesterol levels and low-density lipoprotein cholesterol (LDL-C) showed less dramatic changes. Patterns of lipid and lipoprotein changes were qualitatively similar between men and women. However, greater decreases in serum total cholesterol, LDL-C, and triglyceride levels were observed in participants with high (n = 10) compared with low (n = 10) baseline lipid levels. Cholesterol changes were not affected by anorexiant medications. However, triglyceride levels at week 34 were significantly (p less than 0.025) less in the participants treated with anorexiants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587080 TI - Electrical impedance tomography. A sensitivity region reconstruction algorithm using adjacent drive current injection strategy. AB - The 'sensitivity region' method of back projection is converted from polar drive to adjacent drive current injection strategy and individual sensitivity coefficients incorporated. For each projection sensitivity coefficients for each pixel were established and pixels were grouped together into the 'sensitivity regions'. These contain all pixels that have their largest sensitivity coefficients associated with a particular measurement pair. Back projection of measurement data was performed using these coefficients as the basis of the reconstruction and less sensitive measurement pairs were ignored. Formulae for the back projection are discussed and images from computer simulated data and raw data supplied by Sheffield as part of this concerted action are presented. Comparison with polar current injection strategy is discussed. PMID- 1587079 TI - Long-term weight control study: conclusions. PMID- 1587081 TI - Conductivity interface modelling with dipoles by means of optimal control and boundary element methods in impedance tomography. AB - Optimal control techniques have been combined with Alessandrini's singular perturbation method and Wexler's algorithm to reconstruct images in impedance imaging. We have also considered an integral formulation of the potential problem, which has led us to introduce an array of dipoles whose position, orientation and length can be optimised to model the conductivity discontinuities. PMID- 1587082 TI - Common-mode feedback in electrical impedance tomography. AB - When a current is injected into a body, in addition to the voltage profile developed on the surface, a common-mode voltage (CMV) which produces errors in the measurement also appears. The great accuracy needed to reconstruct images in electrical impedance tomography (EIT) requires the use of differential amplifiers with a high common-mode rejection ratio (CMRR) to avoid this error. Nevertheless, the effective CMRR is lower than the differential amplifier ratio due to mismatches in the electrode impedances and other circuits in the measurement channel. The use of common-mode feedback (CMFB) is an alternative to reducing the error produced by the CMV. The stability of the feedback loop is analysed for a broadband system. Simulation and experimental results show that it is possible to obtain an improvement of 40 dB in the measurements at frequencies of up to 10 kHz. PMID- 1587083 TI - Back-projection distortions in applied potential tomography images due to non uniform reference conductivity distributions. AB - An investigation was conducted to determine and quantify the distortions in applied potential tomography (APT) images reconstructed from data originating from bodies of non-uniform reference conductivity distributions. The results show that the distortions in the images are dependent on the reference conductivity distribution and on whether the images are formed by back projection along the assumed equipotentials of a uniform reference conductivity distribution or along the equipotentials of the true conductivity distribution. We believe that this last finding is significant since our previously held expectation, similar to that of Yorkey and Webster (1987), that back projection along the true equipotentials of the reference conductivity distribution should result in an accurate reconstruction, is shown to be incorrect. PMID- 1587084 TI - Neural networks for electrical impedance tomography image characterisation. AB - The Southampton electrical impedance tomography (EIT) system used a Sheffield data acquisition unit and a PC based 'Harlequin' transputer card to reconstruct and display images of the distribution of internal conductivity within the thorax. The system produces real-time images relating to both cardiac and pulmonary function. As a first step towards diagnosis using these images neural nets have been applied to the identification of regions of interest in the EIT images for which some activity with time, such as ventricular ejection, is sought. This paper addresses the use of a back-projection network to identify characteristic regions within the images. The network facilitates the production of automated real-time activity plots by defining their effective extent in the images of specific organs. The application is novel within the medical imaging field as the aim is to use neural networks for real-time image analysis. PMID- 1587085 TI - Noise and spatial resolution of a real-time electrical impedance tomograph. AB - The Sheffield real-time electrical impedance tomograph produces 25 images per second, using 16 electrodes with adjacent-pair current drive and non-iterative image reconstruction. We describe the data acquisition timing of this instrument and present quantitative measurements of its signal-to-noise ratio and spatial resolution. PMID- 1587086 TI - Electrical impedance tomography. Solving anisotropic mixed boundary value problems by means of the boundary element method. AB - In a previous study we have shown that an anisotropic volume conduction problem involving the Neumann condition at the outer surface of a volume conductor can be solved by means of the boundary element method by applying an appropriate coordinate transformation (Zhou and van Oosterom 1991). In this paper we will show that this approach can also be applied to solve the anisotropic mixed boundary value condition problems studied in electrical impedance tomography (EIT). Results are presented of numerical computations, which were carried out for a volume conductor of irregular (torso) shape. PMID- 1587087 TI - Analysis of three-dimensional software EIT (electrical impedance tomography) phantoms by the finite element method. AB - In electrical impedance tomography, two-dimensional (2D) finite element solutions are used in the imaging algorithms. It is assumed that a major part of the current flowing through the object is restricted to the measurement plane (i.e. the plane determined by the electrodes which are used for measuring voltage differences) and the current flowing elsewhere is negligible. However, there is usually a three-dimensional (3D) variation of the conductivity distribution and if there are regions of high contrast close to the measurement plane, the measured voltage values may be considerably affected. In this work a 3D finite element analysis is utilised to demonstrate the previously mentioned effects. Examples are given to show the measured voltage differences for conductivity distributions which are identical on the measurement plane but different elsewhere. PMID- 1587088 TI - Application of the boundary element method to the study of boundary potentials in electrical impedance tomography. PMID- 1587089 TI - Electrical impedance tomography. The provision of an electric field of controllable penetration into a cylinder. AB - If a cylinder carries on its surface an electric charge of a density which is constant in the axial direction, but which varies sinusoidally with an integral number of wavelengths around the circumference, then inside the cylinder the electric field has its maximum value at points adjacent to the surface, and reduces continuously as the axis is approached. The rate of reduction increases with the number of wavelengths. A rotating cylinder of such charge may be simulated by a number (divisable by three) of equally spaced conducting bars mounted longitudinally on the surface of a stationary cylinder, the bars being connected in sequence to the lines of a three-phase voltage supply. The number of wavelengths of charge around the circumference can be varied by the connection together of a chosen number of adjacent bars effectively to form a single bar, and so fields of varying penetration depths can be produced from a fixed frequency supply. The variation of the resulting currents would be related to the corresponding variation in the complex conductivity of the cylinder material. PMID- 1587090 TI - Improvements in the hardware of the Lund impedance tomography system. AB - The objective of this study is to improve the quality of the hardware of the existing Lund impedance tomography system. Improvement in the current generator and different isolation proposals are presented. PMID- 1587091 TI - Electrical impedance tomography. Determination of the boundary of an object inserted into a water-filled cylinder. AB - In order to circumvent the electrode position determination problem in static electrical impedance tomography, it is possible to insert the object to be imaged into a water-filled cylinder on which the electrodes are at fixed and known positions. It has previously been shown that if the boundary of the internally placed object and the conductivity of the salty water in the cylinder are known, then a significant improvement in the conductivity image of the object is obtained. An algorithm for finding the boundary of an internally placed object is developed based on the finite element method (FEM). The boundary is assumed to obey a parametric model and the parameters are estimated by inverting a matrix representing the sensitivity of the boundary voltage measurements to parameter variations. The algorithm assumes that the object's internal conductivity is uniform and known. Simulation studies show that if the internal conductivity is not uniform to the extent found in the arm cross-sections, up to 9% error in the boundary, as measured from a centrally placed reference point, may result. It is also shown that if previous knowledge about the boundary shape is used to model the boundary with fewer numbers of parameters, then the boundary may be found with less error. PMID- 1587092 TI - A hybrid phantom for electrical impedance tomography. AB - One of the design considerations for electrical impedance tomography phantoms is that they must be easy to model accurately. This paper describes a phantom with this property. Experimental results from its evaluation and testing are given. PMID- 1587093 TI - The modulation transfer function in impedance imaging. AB - The concepts of the point spread function (PSF) and its Fourier transform, the modulation transfer function (MTF) are introduced to evaluate an impedance imaging system. The effects of some practical factors which should be taken into account in calculating the MTF are analysed. Experimental results from the groups in Sheffield, Barcelona and Toulouse are presented. PMID- 1587094 TI - Application of electrical impedance tomography to the determination of lung volume. AB - Trans-thoracical electrical impedance measurements on a human subject have been performed using the Sheffield equipment. These measured transfer impedances are compared with computed ones, based on an inhomogeneous, torso-shaped volume conductor, for different values of the overall electrical conductivities sigma l and sigma r of left and right lung. Each measured set of impedances is compared with all calculated sets. The remaining (minimum) residual difference epsilon is used as a measure of the goodness of fit, and the values of sigma l and sigma r for which epsilon is minimal are taken as representing the overall conductivities of the lungs. For data measured at various stages within the respiratory cycle, sigma l and sigma r have been determined. The results are found to relate well to physiology: for a measurement taken at maximum expiration sigma l and sigma r indicate almost homogeneity, whereas for end inspiratory level sigma l and sigma r tend towards values of 0.2, which is a realistic value for the relative conductivity of lung tissue. PMID- 1587096 TI - Blood flow imaging using electrical impedance tomography. AB - It is shown that a real-time electrical impedance tomography (EIT) system can be used to image the flow of saline through the human vascular system. A 10 ml bolus of 0.9% saline injected intravenously distal to an EIT imaging plane allows venous flow to be observed. Measurements on a cylindrical tank with flow along axial conductive tubes have been used to establish that the area under a concentration against time curve can be obtained from the EIT images and used to determine the flow rate down the tube. In vivo results show that flow images of the venous system in a limb can be obtained and that there is adequate sensitivity to follow the passage of a saline bolus though the cardiac chambers. PMID- 1587095 TI - Electrical impedance measurements for pulmonary disease diagnosis. AB - An investigation of the physical state of the human thorax and the associated thoracic electrical impedance is presented. From an experimental study with 60 subjects (23 without pulmonary disease and 37 with obstruction or restriction) it is concluded that the percentage change in the measured input impedance from the predicted value is a good index to estimate the size of oedema and the physical state of the lungs. These results are in good agreement with the theoretical analysis of the problem and the patient's physical state. PMID- 1587097 TI - Monitoring body fluid distribution in microgravity using impedance tomography (APT (applied potential tomography)). AB - For an astronaut, the excitement of going into orbit is accompanied by a shift of 1 to 1.5 l of fluid from the legs into the upper body. Information on the way the redistributed fluid is handled by the body is very useful to space physiologists studying the process of adaptation to zero-gravity. Applied potential tomography (APT) can be used to image changes in fluid distribution. To ensure that the technique was capable of measuring fluid shifts induced by changing gravitational forces on the body, a standard Sheffield APT system was used to study several subjects during the eight ESA parabolic flight campaign. The results clearly demonstrated the feasibility of using APT for monitoring fluid redistribution during space flight. A battery-powered, body-worn APT system has now been developed for use in space. The equipment was tested on the eleventh parabolic flight campaign. The data collected with the miniaturised system was comparable to that obtained in the earlier experiment. Ergonomic tests indicated that the equipment is no more difficult to operate and maintain under weightless conditions than on earth. The system is undergoing space qualification tests in Munich. If no problems arise it will be used by German astronauts on missions to MIR and Skylab. PMID- 1587098 TI - Experimental assessment of electrical impedance imaging for hyperthermia monitoring. AB - Two experimental studies are presented that attempt to assess the use of electrical impedance tomography (EIT) to map thermal changes deep in the body. The first was a joint study between our group in Sheffield and the Daniel den Hoed Cancer Center in Rotterdam, funded by the COMAC-BME Hyperthermia project. Phantom and in vivo experiments were conducted with a deep heating ring capacitive hyperthermia device; the results highlighted some of the inherent problems (electromagnetic interference, nonuniform sensitivity) that remain to be solved for this application. The second experimental study involved heating the stomachs of volunteers by pumping known quantities of liquid (a salt/glucose solution, conductivity 5 mS) at controlled temperatures (25, 37 and 47 degrees C) in and out of the stomach via a nasogastric tube. Results indicated that the level of thermal change induced by these liquids could be reproducibly measured by impedance imaging. Both studies were a further step in assessing the capabilities of EIT for noninvasive monitoring of deep body hyperthermia. The results are encouraging and indicate the value of continued development of EIT for non-invasive thermometry. PMID- 1587099 TI - Optimal electrolytic chloriding of silver ink electrodes for use in electrical impedance tomography. AB - The electrode-electrolyte interface impedance may be simplistically modelled by an equivalent circuit comprising a resistance, RTOTAL, in series with an empirical, constant phase angle impedance, ZCPA. This pseudo-capacitance can be thought of as representing empirically the non-faradaic, double layer capacitance in the presence of specific adsorption and surface roughness effects. RTOTAL is the sum of the lead and electrolyte resistances. Depositing a thin layer of silver chloride on silver electrodes can yield improved electrical performance characteristics (potential and impedance) when used in conjunction with a chloride gel. An electrolytically deposited AgCl layer tends to have a rough surface profile thus leading to an increase in the effective interface area. This gives rise to a decrease in RTOTAL and ZCPA, both of which are desirable. Unfortunately AgCl is a relatively poor conductor. Increasing layer thickness causes RTOTAL to increase, thus adversely affecting the inter-electrode impedance at high frequencies. Electrode systems for use in electrical impedance tomography therefore require only relatively thin layers of AgCl. PMID- 1587100 TI - Pulmonary perfusion and ventricular ejection imaging by frequency domain filtering of EIT (electrical impedance tomography) images. AB - While EIT images can produce clinically useful qualitative information, the extraction of quantitative data is essential in clinical monitoring. In the case of imaging of the thorax the parameters available relate to cardiac activity and pulmonary perfusion. Imaging the relatively small changes in the resistivity of the lungs due to pulmonary perfusion in the presence of noise and the larger ventilation component is difficult. Suggested solutions involve multiple time averaging of cardiac gated data or reconstructed images. The required number of data frames for this type of processing is large (at least 100 cardiac cycles). Because the ventilation and perfusion components of the resistivity signals are well separated in the frequency domain, they can be differentiated by filtering. We report the results of this analysis which requires a data collection period of typically 15 s. PMID- 1587101 TI - Measurement of pharyngeal transit time by electrical impedance tomography. AB - The feasibility of using electrical impedance tomography (EIT) for measuring pharyngeal transit time has been investigated. Imaging sequences were obtained on the neck in a group of eight healthy subjects when swallowing solutions of different electrical conductivities. The solutions used were aqueous Dioralyte (1.5 S m-1) and tap water (0.04 S m-1). The effects of movement upon the images were large compared with the changes due to the solutions, but these were cancelled by a subtraction technique. The mean value of the EIT pharyngeal transit time parameter was 370 +/- 120 ms. EIT has the advantage that repeated measurements could be performed without fear of hazard in contrast to the established technique of video fluoroscopy which involves ionising PMID- 1587102 TI - Raw data interchange format for electrical impedance tomography. AB - A data interchange format is described to allow groups working on electrical impedance tomography (EIT) with disparate algorithms and instruments to compare results. The procedure has been tested by exchanging data by e-mail. The format is defined in the appendix. PMID- 1587103 TI - The performance of integrated transconductance amplifiers as variable current sources for bio-electric impedance measurements. AB - Multiple applied current impedance measurement systems require numbers of current sources which operate simultaneously at the same frequency and within the same phase but at variable amplitudes. Investigations into the performance of some integrated operational transconductance amplifiers as variable current sources are described. Measurements of breakthrough, non-linearity and common-mode output levels for LM13600, NE5517 and CA3280 were carried out. The effects of such errors on the overall performance and stability of multiple current systems when driving floating loads are considered. PMID- 1587104 TI - Differential synchronous demodulation for electrical impedance tomography. AB - A differential synchronous demodulator developed for electrical impedance tomography applications is presented. The demodulator proves to have high CMRR due to its architecture. PMID- 1587105 TI - Performance of a differential synchronous demodulator for electrical impedance tomography. AB - The performance of a differential synchronous demodulator is presented. This demodulator is part of an electrical impedance tomography system developed by our group. In addition a technique for common-mode correction instead of common-mode feedback is proposed. A series of measurements as a function of the common-mode signal is given. PMID- 1587106 TI - Electrical impedance tomography systems based on voltage drive. AB - At the ESAT-MICAS research facility in Leuven, several EIT systems have been designed and realised. The latest hardware set-up makes use of a PC to control the data collection and to reconstruct the images. A voltage drive strategy and no common-mode feedback are some of its specific characteristics. The function generator produces signals with a frequency between 10 and 100 kHz, so multifrequency images can also be produced. Static images have already been obtained and (semi-)real time imaging is possible with our latest mark IV system. This system has 16 bit analogue-to-digital convertors and is capable of taking 50 x 10(3) samples/s. PMID- 1587107 TI - Electrical impedance tomography. Electrode current determination from programmable voltage sources. AB - The accuracy requirements for adaptive current electrical impedance tomography (EIT) measurements exceed the capability of available current sources. A new architecture for an EIT system is described in which the electrode current is set indirectly from a voltage-drive structure. A numerically inverted admittance matrix, obtained from current measurements and driving voltages, has been used to achieve the desired current pattern from programmable voltage sources. PMID- 1587108 TI - Imaging the complex impedance in electrical impedance tomography. AB - Measuring the reactive component of the bio-impedance enables a full characterisation of the frequency response of a tissue. The amplitude of the reactive component is relatively small in the frequency range generally used in electrical impedance tomography (EIT). Its measurement is therefore more sensitive to errors. At higher frequencies, the amplitude of this component increases, which increases the signal-to-noise ratio. The stray capacitance, however, also increases and the front-end circuit must be designed carefully. The purpose of the present study is to show the feasibility of the collection of data at relatively high frequencies; 31.25 and 250 kHz were used. Both the real and reactive components were used to reconstruct images from capacitive targets. This study suggests that it may be possible to use multifrequency systems to determine the parameters of frequency loci and therefore tissue characterisation. PMID- 1587109 TI - Electrical impedance tomography. An improved design of voltmeter for semi parallel data acquisition. AB - The design and implementation of high performance differential voltmeters for semi-parallel data acquisition are described. The general requirements and specific conditions encountered in electrical impedance tomography (EIT) for accurate measurements are analysed. The major parameters are common-mode rejection and bandwidth. A specific implementation of the voltmeters, with separate DC supplies and independent signal references, is described. This arrangement, in which each voltmeter follows the input signal, automatically cancels any common-mode voltage present at the input. The signal is fed to the remainder of the instrumentation through a transformer. The use of a reduced number of components contributes to the minimisation of the inter-channel variations. Furthermore, the geometrical distribution of the voltmeters around the object minimises the length of electrode wires, also reducing the input capacitance. The number of modular voltmeters and DC/DC converters is 32. The common-mode rejection of these voltmeters is greater than 72 dB in the frequency range 3.6-560 kHz. In conclusion, the proposed solution ensures a minimisation of common-mode errors and enables the use of a 250 kHz frequency. PMID- 1587110 TI - Electrical impedance tomography. Improved wideband, high CMRR (common mode rejection ratio) instrumentation amplifier. AB - A wideband high CMRR instrumentation amplifier is described. Based on a previously reported current-mode design, the improved amplifier features excellent CMRR performance of better than 60 dB up to 200 kHz with unity differential gain. PMID- 1587111 TI - Electrical impedance tomography. Technical and experimental problems encountered in impedance spectroscopy in the alpha and beta dispersion regions. AB - The main experimental problems (temperature, electrode, polarisation, non uniformity of electric field, non-homogeneity of biological material) of impedance measurements of biological tissue are discussed. Minimisation of the inherent sources of experimental error is proposed. PMID- 1587112 TI - A broadband system for multifrequency static imaging in electrical impedance tomography. AB - A widely accepted method for static imaging in electrical impedance tomography (EIT) is to measure at two frequencies. The choice of measurement frequencies is application-dependent because some different tissues cannot be distinguished when using two fixed frequencies. We have developed a system that generates signals from 8-10(3) kHz and applies two of these signals simultaneously to the body through a broadband current mirror. Great care has been taken in the design of the current injection multiplexer in order to keep the current source output capacitance as low as possible. Furthermore design of the layout of the patient interface board, in order to reduce feedthrough capacitances, also needs great care. Other parameters for driving and detection sections have been designed according to our results from FEM and circuit simulations including skin and electrode effects. Simulations using FEM with available tissue impedance data and preliminary measurements in a discrete phantom show that static imaging is possible for both the real and imaginary parts of the impedance. PMID- 1587113 TI - Multifrequency electrical impedance tomography. AB - Multifrequency tomography may be conveniently achieved by sequentially sweeping the probing drive current and measuring the resultant voltages at each frequency. If events change during measurement comparisons between frequencies cannot be made. Mixing several frequency components may decrease acquisition time but increase the complexity of the instrumentation. A third method is described using Fourier transformation that enables simultaneous multifrequency measurements without an increase in instrumentation. A signal is constructed from a number of sinusoidal components of known amplitude and phase. This group of components is transformed into a time series by the inverse Fourier transform and applied to the object via a voltage or current source. Transforming the detected voltage back into Fourier components will provide the frequency response of the object. Data are collected in this way for all projections and tomograms reconstructed for each frequency. This has the advantage that no special detector is required; both in-phase and quadrature components are available and systematic errors may be easily corrected by software. This technique is demonstrated using a resistor phantom with known frequency-dependent perturbations. PMID- 1587114 TI - Electrical impedance tomography. Determination of impedance of tissue in the frequency range 10(-6)-20 MHz: preliminary results. AB - In order to characterise small samples of tissue by complex impedance measurements between 10(-6) and 20 MHz, an experimental set-up is proposed. This paper describes the methodology used and presents some preliminary results. PMID- 1587115 TI - Imaging the complex impedance of the thorax. AB - Respiration-related changes in the complex impedance were obtained on the thorax in three volunteers. The real part of the image clearly showed the lungs as regions of increased conductivity on expiration. The imaginary part of the image, reflecting changes in the ratio of permittivity to conductivity, showed a central negative region surrounded by a positive region extending to the periphery of the lungs. These features may be due to movement of the diaphragm and liver within the sensitive volume during respiration. PMID- 1587116 TI - Electrical impedance tomography. Comments on reconstruction algorithms. PMID- 1587117 TI - Reconstruction of impedance images using a modified perturbation method. AB - A modified perturbation method (MPM) arising from the replacement of the sensitivity matrix by the Jacobian matrix is presented. Our results have been made using an array processor board with four T-800 INMOS transputers. The numerical algorithm has been matched to the new system and the procedure reached a minimum 50 times faster than for a single PC/AT with mathematical co-processor. Several phantoms have been reconstructed. From the results one can see the applicability of the MPM algorithm to complicated models. PMID- 1587118 TI - Electrical impedance tomography using induced and injected currents. AB - A two-dimensional forward problem formulation is introduced for electrical impedance tomography (EIT) using induced currents. The forward problem is linearised around a certain resistivity distribution and the inverse problem is formulated as a solution of a linear system of equations. Sensitivity of boundary measurements to resistivity variations are analysed for spatially uniform, linear and quadratic fields. The formulation, however, is suitable for studying the effects of a general magnetic field applied to induce the currents in the conductive object. A similar inverse problem formulation is also developed for EIT using injected currents. Simulation studies are performed by reconstructing images of a simulation distribution using both methods separately with generalised inversion. It is also shown that the derived formulations for the inverse problems of the two methods can be combined to solve a larger set of equations with a greater number of independent measurements. PMID- 1587119 TI - [Does an efficacious adjuvant treatment exist in resected colonic carcinoma?]. AB - The prognosis of colon cancer after curative resection is mainly related to the onset of metastases, and especially of liver metastases. In order to prevent metastatic recurrences, the value of adjuvant medical therapy is widely admitted. The aim of the present review was to analyse the conclusions of the main recent randomized trials assessing the comparative value of different adjuvant protocols. The results obtained using either classic systemic infusion or intraportal infusion, which is mainly used with the intent of preventing liver metastases, are reported. At term of this review, we conclude that: adjuvant chemotherapy using combined drugs (5-Fluorouracil + Methyl CCNU, 5-Fluorouracil + Oncovin) did not prove to be more active than 5-FU alone. the beneficial action of a combined 5-FU + Levamisole regimen has been clearly demonstrated for patients with a Dukes C tumor. intraportal adjuvant therapy has been shown to be effective for patients with Dukes B tumors in only one limited trial but this remains to be confirmed. On the basis of the present data, new adjuvant programs using combined chemotherapeutic and immunotherapeutic compounds, and combined systemic and regional infusion, can be envisaged. PMID- 1587120 TI - [Raynaud's phenomenon. The clinical picture, physiopathology and therapeutic criteria]. PMID- 1587121 TI - [The importance of estradiol treatment by the transdermal route in preventing postmenopausal osteoporosis]. AB - The authors selected 18 women in surgical menopause in order to evaluate the validity of estrogen treatment for the prevention of postmenopausal osteoporosis. Ten of these patients were given transdermal estradiol continuously for 12 months while the remaining eight served as untreated controls. Urinary hydroxyproline and bone density were assessed before and at previously determined intervals during treatment: the results showed the importance of estrogen replacement therapy for the prevention of postmenopausal osteoporosis. PMID- 1587122 TI - [Colonic radiography by double-contrast enema in the elderly patient with the use of trimebutine maleate]. AB - About 15% of hospitalizations of patients over 65 are due to disorders of the colon which means that accurate analysis of history and clinical and instrumental investigation are mandatory. Our attention has been focused on x-ray examination using a double-contrast enema which, together with endoscopy, permits to diagnose colonic disorders with significant reliability. Our aim was to adapt the method to the special needs of the patient over 65 by employing the active substance trimebutine maleate (M.T.) as a "contact" pressure-lowering agent. Thirty-five subjects aged 65-75 with pathologies implying a risk for the use of parasympatholytic agents were examined. None of these patients showed side effects. It can therefore be said that the use of M.T. as a hypotonic agent in double-contrast enemas is an indisputable diagnostic aid. PMID- 1587123 TI - [The appearance of a PNH clone during enzymopenic hemolytic anemia]. PMID- 1587124 TI - Analysis of high-angle synchrotron x-ray diffraction patterns obtained from macular dystrophy corneas. AB - Six macular dystrophy corneas from six individuals were investigated by synchrotron x-ray diffraction. Immunochemical evidence demonstrated that five of the patients had type I macular corneal dystrophy and that one had type II. Analysis of the high-angle x-ray diffraction patterns showed that the intermolecular spacing of macular dystrophy corneal collagen increases with hydration from the dry state in a fashion similar to the intermolecular spacing of normal human corneal collagen. The high-angle x-ray diffraction pattern from all six corneas contained two "extra reflections" not obtained from other human corneas, normal or pathologic. The reflections, which arise from 4.61 and 9.62 A periodic structures, are independent of the type of macular dystrophy. Furthermore, their position is independent of corneal hydration. We propose that a glycosaminoglycan structure is the origin of the unique extra reflections. PMID- 1587126 TI - Survival of Streptococcus pneumoniae in corneal storage media. AB - The Cincinnati Eye Bank had six corneoscleral rims in which Streptococcus pneumoniae was cultured after preservation in corneal storage media. To determine the survival of this organism under conditions common for corneal storage, gentamicin-supplemented McCarey-Kaufman (M-K) medium and chondroitin sulfate/Dextran medium (Dexsol, Ciron Ophthalmics, Irvine, CA, U.S.A.) were inoculated with S. pneumoniae and kept at 4 degrees C. Thioglycollate broth plus 10% rabbit serum (Thio-S) and tryptic soy broth (TSB) served as growth controls. At day 14 after inoculation of 10(5) colony-forming units (CFU)/ml, Dexsol showed a 1-log decrease in bacterial concentration, the M-K medium a 2-log decrease and Thio-S a 4-log decrease, whereas TSB showed no detectable organisms. By day 21 Dexsol had only a 2-log decrease in bacteria. These data suggest that corneal storage medium supplemented with gentamicin does not exert bactericidal activity against S. pneumoniae and may actually support its survival at 4 degrees C. PMID- 1587125 TI - Variations in corneal wound healing after radial keratotomy: possible insights into mechanisms of clinical complications and refractive effects. AB - Ultrastructural and histopathologic analysis was performed on three human corneal specimens for variable and complicated refractive outcomes 1-2 years after radial keratotomy. Specimens were obtained immediately postsurgery after microkeratome resection with homoplastic lamellar keratoplasty (two cases) and penetrating keratoplasty (one case) for correction of glare, severe astigmatism, overcorrection, and/or double vision. All three cases showed variability of wound healing and delayed corneal wound healing sites; epithelial retention cysts, and/or absence of stromal scar collagen that was not dependent on the length of time after surgery. Two of the three radial keratotomy specimens also contained extensive duplication of the superficial corneal epithelial basal lamina. When present, the thickened basal lamina (3-6 microns in thickness) was seen between all incisions evaluated and appeared to extend from the central optical zone out to the periphery of the lamellar button. The one full-thickness keratoplasty specimen showed focal loss of underlying endothelial cells with occasional migrating cells seen by scanning electron microscopy. These data support previous findings that delayed corneal wound healing with epithelial retention cysts remains the most common histopathologic alteration after radial keratotomy. The effects of variations and delay in wound healing between individuals could explain the lack of predictability of refractive outcome and continuing refractive instability in long-term follow-up after single or repeat radial keratotomy surgeries. PMID- 1587127 TI - Comparison of corneal preservation media for corneal hydration and stromal proteoglycan loss. AB - Changes in the composition of stromal proteoglycans (PGs) have been previously demonstrated in corneal edema, wound healing, and disease. To examine if PGs are lost during corneal preservation, rabbit corneal PGs were radiolabeled in situ with 35S-sulfate and 3H-glucosamine, excised and stored in either modified McCarey-Kaufman medium (MMK), K-Sol (Coopervision-Cilco, Bellevue, WA, U.S.A.), corneal storage medium (CSM), or Dexsol (Chiron Ophthalmics, Irvine, CA, U.S.A.) for up to 14 days. The percentage of total radio-label lost was significantly greater from de-epithelialized corneas (p less than 0.05) and from corneas stored in CSM (p less than 0.05) or K-Sol (p less than 0.05). Corneas stored in CSM for 4 and 7 days were significantly more hydrated than corneas stored in MMK, K-Sol, or Dexsol. After 14 days of storage, all corneas were hydrated above control values with the Dexsol-stored cornea showing the least hydration. Results suggest that loss of stromal PGs during corneal storage is reduced with epithelial integrity and with preservation media containing dextran. PMID- 1587128 TI - Cryopreservation of rabbit and cat corneas at -18 to -24 degrees C. AB - A simple method of corneal cryopreservation, in which corneas were frozen at -18 to -24 degrees C, was examined. Rabbit and cat corneas were placed successively in solutions of 50% fetal calf serum in McCarey-Kaufman medium with an increasing glycerol and glucose content. They were then frozen and stored in a -20 degrees C domestic freezer. Rabbit corneas stored in this way were examined in vitro by light and scanning electron microscopy, and both rabbit and cat corneas were also assessed after orthotopic allotransplantation into adult recipient animals. Functional corneal grafts were obtained with rabbit and cat tissue that had been cryopreserved for 3-4 weeks and 1 week, respectively. Endpoint analysis (by light and scanning electron microscopy) of grafts that had survived for 50 days indicated the presence of an intact corneal endothelial monolayer. The corneal endothelium slowly degenerated as the storage time was increased. Importantly, however, the endothelium appeared to withstand the freezing and thawing processes and we conclude that it may be possible to store corneas at temperatures above 196 degrees C, without the need for complex, low-temperature cryopreservation systems. PMID- 1587129 TI - Confocal microscopic studies of living rabbit cornea treated with benzalkonium chloride. AB - The effects of benzalkonium chloride (BAK) on the living rabbit cornea were studied by in vivo Tandem scanning confocal microscopy (TSCM) and confirmed by conventional scanning electron microscopy (SEM). Two drops of saline or phosphate buffered saline (PBS) containing BAK in concentrations of 0.02, 0.01, and 0.005% was applied to rabbit eyes 15 times at 5-min intervals. The solutions were pH 5.5 5.9 (saline) and pH 7.5 (PBS), and osmolarity was 275-280 (saline) and 300-307 mOsm (PBS). Immediately after application of 0.02 and 0.01% BAK, no normal corneal superficial epithelial cells could be imaged by in vivo TSCM. No swelling of the superficial epithelial cells was observed for the control solution without BAK; however, there was a small amount of desquamation. Application of as little as 0.005% BAK caused the superficial epithelial cells to swell and desquamate. The observed desquamation of corneal superficial epithelial cells increased with higher BAK concentrations applied to the eye. One hour after final drug application, inflammatory cells appeared on the surface of the cornea treated with 0.02% BAK. These findings were correlated with SEM observations. Based on the results of this study, we believe that BAK used frequently can produce clinical corneal toxicity and that the cytotoxicity of any topical ophthalmic solutions can be evaluated by in vivo TSCM. PMID- 1587130 TI - Ofloxacin in human serum, urine, and tear film after topical application. AB - We evaluated the systemic absorption of ofloxacin eyedrops in humans and their availability in the tear film. Serum, urine, and tear film concentrations of ofloxacin were measured in 30 healthy women topically treated with 0.3% ofloxacin, in both eyes, four times daily for 10 1/2 days. Serum was collected before the first daily dose on days 1 and 11 and at 18 time points before the second dose. Maximum serum ofloxacin concentrations (1.89 +/- 1.13 ng/ml) after 10 1/2 days of topical dosing were more than 1,000 times lower than those reported after standard oral doses of 300 mg ofloxacin. Urine was collected for the 24-h period after the first daily dose on days 1 and 10. Topical ofloxacin was excreted in the urine primarily in unmodified form and recovery rates were significantly higher on day 10 (76.1 +/- 41.5%) than on day 1 (56.6 +/- 31.6%) (p less than 0.05). Both serum and urine data give evidence to accumulations of ofloxacin over a 10 1/2-day period. The low serum concentration at steady state suggests an extremely low potential for producing systemic effects. No systemic side effects attributable to topical ofloxacin were observed. Mild ocular irritation was reported by two patients while under treatment. Tears were collected 4 h after the first treatment on day 11 and at 5, 10, 20, 30, and 40 min after the second treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587131 TI - Decreased tear osmolarity and absence of the inferior marginal tear strip after sleep. AB - To better understand some of the clinical syndromes that patients experience on eyelid opening in the morning, we examined four patients clinically and measured tear osmolarity immediately after sleep and later in the day. The inferior marginal tear strip was absent, and tear osmolarity was at its nadir on eyelid opening after sleep. We propose a mechanism whereby decreased osmolarity, together with a probable decrease in tear volume, may increase lid-corneal and soft contact lens-corneal adhesion during sleep, and help explain both the development of recurrent corneal erosions on awakening and the tendency of soft contact lenses to adhere to the cornea overnight. PMID- 1587132 TI - Morphologic and physiologic effects of artificial tear formulations on corneal epithelial derived cells. AB - The biological effects of four commercially available artificial tear formulations were evaluated using sensitive in vitro techniques. Two of the formulations contained ingredients implicated in cell damage; the other two products were not chemically preserved, and their components have not been reported to damage corneal tissue. We assayed the effects of these formulations on viability, morphology, and physiology in corneal cell (SIRC) cultures. Their effect on the hydration of excised rabbit corneas was also determined. In all formulations, cell viability declined with time relative to control cells, but the time course varied significantly. Viability remained at 100% for 6 h in an unpreserved carboxymethylcellulose-based product (CMC-U), and decreased to 50% after greater than 16 hours. Viability decreased to 50% in 3 h for the other unpreserved, polyvinyl alcohol-based product (PVA-U), and in 1 h for a hydroxypropylmethylcellulose formulation (HPMC-P) that contains edetate disodium (EDTA). Cells in a preserved formulation (PVA-P), using polyvinyl alcohol as the polymer and containing EDTA and benzalkonium chloride (BAK), failed to survive even 15 min of treatment. Overall, cells treated with the unpreserved products were nearly indistinguishable from those in the control solution with respect to morphology, electrophysiology, and corneal hydration. Also, the relative ranking from least to most deleterious (control less than CMC-U less than PVA-U less than HPMC-P less than PVA-P) was consistent across several measures. Of the preserved formulations, HPMC-P, which contains the chelating agent EDTA as an additive, was less damaging than was PVA-P, which contains two chemicals, EDTA and BAK, that reportedly damage cells. PMID- 1587133 TI - Growth of human corneal endothelium on altered Descemet's membrane. AB - To determine whether Descemet's membrane (DM), which is altered by disease, interferes with endothelial cell growth, healthy human corneal endothelial cells were seeded onto DM from normal corneas and diseased corneal buttons from patients with Fuchs' endothelial dystrophy and pseudophakic bullous keratopathy (PBK). DM was first peeled off the corneal specimens and the endothelial cells removed by trypsinization. A suspension of first-passage corneal endothelial cells (2,000 cells/microliters; obtained from donor eye bank eyes and grown in Dulbecco's minimal essential medium with 10% fetal bovine serum and 1.5% chondroitin sulfate) were seeded on DM. Epidermal growth factor (10 ng/ml) and insulin (1 U/ml) were added to the medium after seeding cells on the DM. The cells attached and flattened within 1 hour and reached confluency in 1 week on normal DM. Cells grown on DM from corneas of patients with Fuchs' endothelial dystrophy also flattened and grew to confluency in 1 week. Cells grown on DM from corneas of patients with PBK did not grow to confluency. Further studies with bovine and rabbit corneal endothelial cells showed similar growth pattern to human cells. These data indicate that DM from corneas of patients with Fuchs' dystrophy does not interfere with the growth of corneal endothelial cells but that DM from corneas of patients with PBK does interfere with cell growth. PMID- 1587134 TI - Axial length in keratoconus. AB - Axial length is a major determinant of ocular refractive power that has not been well established for keratoconus eyes. The purpose of this study was to establish the mean and range of axial length among both keratoconus eyes with no previous surgery and postkeratoplasty keratoconus eyes, and to determine if there is a significant reduction of axial length following variations in surgical techniques in penetrating keratoplasty. The axial length of 157 keratoconus eyes with no previous surgery was measured using applanation ultrasonography. The mean axial length measurement was 24.39 (+/- 1.13 mm), with a range of 21.82-28.69 mm. The axial length of 66 postkeratoplasty keratoconus eyes was similarly measured. The mean axial length measurement was 24.10 (+/- 1.22 mm), with a range of 21.83 26.87 mm. These values are not significantly different from the axial length mean and range found among emmetropic eyes. A significant shortening of the axial length (F = 5.2, p = 0.04) was obtained in the postoperative penetrating keratoplasty eye if the donor trephine was 0.3 mm smaller in diameter than the recipient trephine. The axial length of individual keratoconus eyes is a major factor in determining postoperative refractive error. It therefore becomes important when considering variations in surgical procedures to reduce postoperative myopia. PMID- 1587135 TI - Bilateral progressive essential iris atrophy and keratoconus with coincident features of posterior polymorphous dystrophy: a case report and proposed pathogenesis. AB - We report the first case known to us of an apparent bilateral association of essential iris atrophy (EIA) and keratoconus (KC), with coincident features of posterior polymorphous dystrophy (PPD). Based on this case and the published natural history and findings of both the irido corneal endothelial (ICE) syndrome and PPD, we propose a new hypothesis for the pathogenesis of the ICE syndrome with associated KC and/or PPD. We suggest that, similar to the genetics of retinoblastoma, the predisposition for either the ICE syndrome or for PPD is inherited as an inactive allele, the so-called "first hit." Inactivation of the second allele, or "second hit," which could occur at any time, might be the product of the background mutation rate or of an environmental trigger. Dedifferentiation or an abnormality in normal development could occur after the first or second hit, resulting in varying clinical patterns. We also concur with other investigators that PPD could be part of the spectrum of the ICE syndrome, owing to similarities in their clinical presentations, histopathology, specular and electron microscopy, and natural history. PMID- 1587136 TI - Superior limbic keratoconjunctivitis in identical twins. AB - The first two cases of superior limbic keratoconjunctivitis occurring in identical twins are reported. In both cases the symptoms began 16 years ago and have never permanently responded to numerous topical medications or to bilateral resection of the superior bulbar conjunctiva. PMID- 1587137 TI - Corneal argyrosis associated with silver soldering. AB - We report a patient who developed corneal argyrosis secondary to occupational silver soldering. Clinically, the cornea was notable for a green-brown discoloration localized to Descemet's membrane by slit-lamp biomicroscopy. Silver particles were identified within the anterior three eighths of Descemet's membrane by light and electron microscopy and energy-dispersive x-ray microanalysis. To our knowledge, the association between corneal argyrosis and silver soldering has not been previously reported. PMID- 1587138 TI - Corneal transplantation in a patient with congenital sensory neuropathy. AB - We describe penetrating keratoplasty for corneal scarring in a patient with congenital sensory neuropathy and repeated self-mutilation. This patient underwent a successful penetrating keratoplasty but suffered a series of postoperative complications necessitating three repeat grafts. Some of these complications were attributable to decreased corneal sensation while others were caused by self-mutilation. Since his last penetrating keratoplasty 4 years ago, this patient has had functional visual acuity. PMID- 1587139 TI - Trichiasis preceding conjunctival changes in cicatricial pemphigoid. PMID- 1587140 TI - Capsulorhexis for cataract extraction during keratoplasty. PMID- 1587141 TI - Acanthamoeba polyphaga panophthalmitis. PMID- 1587142 TI - Interaction of drugs with branched DNA structures. PMID- 1587143 TI - Regulation of antibody production mediated by Fc gamma receptors, IgG binding factors, and IgG Fc-binding autoantibodies. AB - Fc receptors (FcRs) are immunoglobulin-binding structures that enable antibodies to perform a variety of functions by forming connections between specific recognition and effector cells. Besides eliciting cytotoxicity, inducing secretion of mediators and endocytosis of opsonized particles, FcRs are involved in the regulation of antibody production, both as integral membrane proteins and as soluble molecules released from the cell surface. Most FcRs belong to the same family of proteins as their ligands (immunoglobulin superfamily). This review contains recent data obtained by use of monoclonal antibodies and cloning studies on FcRs and FcR-like molecules. The importance of fine specificity of receptor binding site(s)--that of the conformation of FcRs and their ligands in triggering signaling mechanisms--is analyzed. The regulatory function of membrane-bound and released FcRs; the correlation between cell cycle, FcR expression, and release; as well as the possible mechanisms of these phenomena are discussed. PMID- 1587144 TI - Zinc uptake by primate retinal pigment epithelium and choroid. AB - We studied zinc uptake by nonhuman primate retinal pigment epithelium (RPE) and choroid, using 65Zn as a probe. With intravenously administered 65ZnCl2, virtually all detectable tracer was lost from the plasma after 20 hours but the pigment epithelium-choroid showed prominent uptake and retention. Plasma concentrations of oral 65ZnO remained high 20 hours after feeding. Uptake and retention of orally administered 65Zn as 65ZnO from the bloodstream by the RPE/choroid was avid in both young and old animals. Excretion in urine and feces was minimal. All pigmented ocular tissues took up and retained 65Zn. A survey of total zinc content of human and nonhuman primate ocular tissues showed that the pigmented tissues had consistently higher concentrations of zinc. Our results demonstrate for the first time direct uptake and retention of zinc from the blood by primate RPE and other ocular tissues. PMID- 1587145 TI - Developmental expression of S-antigen in fetal human and rat eye. AB - Development expression of S-antigen and its mRNA in human and rat fetal retina was studied by immunocytochemical and in situ hybridization techniques. Immunocytochemistry indicated that S-antigen was present after 4 months gestation in the fetal human retina. In the rat, S-antigen was detected in the retina only after birth. In situ hybridization studies indicated that the S-antigen mRNA was present at 13 weeks gestational age in the human and at 15 days in the rat embryo. S-antigen mRNA was expressed not only in the retina but also in ocular tissues of neural crest origin in the fetus. PMID- 1587146 TI - The effects of L-and D-ascorbic acid administration on retinal tissue levels and light damage in rats. AB - To assess the protective effect of ascorbic acid in retinal light damage of rats, we have determined the uptake and retinal tissue distributions of its L- and D- stereoisomers following interperitoneal or intraocular injections. The effects of intense-intermittent light exposure and darkness on tissue ascorbate were compared by measuring its levels in retina and retinal pigment epithelial tissues at various times after administration. The protective effects of the two forms of ascorbate against retinal light damage were also compared by measuring rhodopsin levels 2 weeks after intense light exposure. After interperitoneal injection, both forms of ascorbic acid were higher in the retinal pigment epithelial-choroid scleral complex (eye cup) than in the retina. Over a 2 hr post-injection period, L-ascorbate in the eye cup was 2 to 4 fold higher than normal (10-11 nmol); D ascorbate levels were between 15 and 30 nmol. During the same period retinal L ascorbate was just above normal (12-14 nmol), whereas less than 5 nmol of D ascorbate was present. When ascorbate was given by the intraocular route the opposite effect was found. During the 2 hr post-injection period retinal L ascorbate levels were 2 to 5 fold higher than normal; D-ascorbate was between 25 and 50 nmol/retina. Within 1 hr post-injection, L-ascorbate in the eye cup was near normal and D-ascorbate levels were 10 nmol or less. In uninjected rats perfused with normal saline, the endogenous L-ascorbate was distributed 55% in the retina with 9% and 36%, respectively, in the RPE-choroid and sclera. Ten thirty min after interperitoneal peritoneal injection about 40% of the L ascorbate was present in the retina with 17% and 44% in the RPE-choroid and sclera. Total ascorbate (L + D) levels in the same tissues of D- injected rats were similar to those found for rats given L-ascorbate. Following 7 hrs of darkness, tissue ascorbate levels in the injected rats decreased to approximately the same levels present in uninjected animals. For rats exposed to intense light average retinal ascorbate levels decreased further, while RPE-choroid and scleral levels were largely unchanged from the dark control levels. About 50% of the tissue ascorbate was present in the retina 10-30 min after intraocular injection. The RPE-choroid contained between 10 and 14% of the ascorbate, with 35-40% present in the sclera. Retinal ascorbate levels remained high in the injected eyes following 2.5 hrs of darkness, but decreased as a result of intense light treatment.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1587147 TI - Thiol adducts of ethacrynic acid increase outflow facility in enucleated calf eyes. AB - Ethacrynic acid (ECA), a sulfhydryl (SH)-reactive diuretic drug, has been shown to increase outflow facility (C) both in living monkey eyes and in the calf eye, in vitro (Epstein et al. 1987). In an attempt to increase the therapeutic index of this drug for potential clinical use in glaucoma, we explored the effect of various thiol adducts of ECA on C in the calf eye in vitro. These adducts might be expected to liberate ECA by a reversible retro-Michael type reaction. Enucleated calf eyes were perfused at 25 degrees C at 15 mm Hg for 5 hours with various ECA-thiol adducts. ECA-cysteine at 0.25 mM (for each) increased outflow facility 104% compared to 38% in sham manipulated eyes (n-10; p less than .005). A dose response effect was demonstrated from 0.01 mM to 0.25 mM. A relative potency table (for increasing C) was established for several ECA-thiol adducts: Cysteine = cysteamine greater than glutathione greater than N-Acetyl cysteine greater than thiosalicylic acid greater than N-Acetyl cysteamine. This study identifies the potential of utilizing various derivatives of ECA as outflow pathway acting agents. PMID- 1587148 TI - Ciprofloxacin and prednisolone therapy for experimental Pseudomonas keratitis. AB - Rabbit corneas were injected intrastromally with Pseudomonas aeruginosa. Sixteen hours after injection, the rabbits were divided randomly into four treatment groups (3 rabbits/6 eyes per group: 1, ciprofloxacin and prednisolone; 2, ciprofloxacin only; 3, prednisolone only; 4, untreated. Ocular signs of inflammation were graded in a masked fashion by slit lamp examination before injection and 16 and 27 hours after injection. Slit lamp examination scores were significantly lower in eyes receiving ciprofloxacin and prednisolone or prednisolone alone, compared with scores in untreated eyes. Slit lamp examination scores were not significantly lower in eyes receiving ciprofloxacin alone, compared with untreated controls. The numbers of viable bacteria in the corneas treated with ciprofloxacin and in the corneas treated with ciprofloxacin and prednisolone were similar and were significantly less (P less than 0.0001) than those in untreated corneas, indicating that the presence of the steroid did not interfere with the bactericidal action of ciprofloxacin. PMID- 1587149 TI - Reductively methylated, tritiated rhodopsin of high specific activity; a convenient sensitive tracer for use in the radioimmunoassay of rhodopsin. AB - Bovine rhodopsin was subjected to reductive methylation in the dark using formaldehyde and high specific activity sodium borotritide. After purification by gel filtration and affinity chromatography on Concanavalin A-Sepharose, the product retained its immunoreactive properties. [3H]-Reductively methylated rhodopsin (specific activity, 32 Ci/mmole) was suitable for use in radioimmunoassays for rhodopsin, having many advantages over radioiodinated rhodopsin for this purpose. The site of the reductive methylation was shown to be the non-active site lysines with the production of tritiated N-epsilon dimethyllysine and tritiated N-epsilon-methyllysine in a molar ratio of about 1.3:1, respectively. In terms of stability, ease of preparation, and specificity, tritiated, reductively methylated rhodopsin presents itself as a preferable ligand to radioiodinated rhodopsin in many applications, such as the radioimmunoassay. PMID- 1587150 TI - Alterations of energetic metabolite levels by free radicals during optic nerve ischemia. AB - An experimental model of optic nerve ischemia was designed in the rabbit to determine early biochemical alterations, i.e.--changes of high energy phosphate metabolites (ATP and phosphocreatine)--in occlusive and peri-occlusive areas. Vascular occlusion provoked a rapid fall of ATP and phosphocreatine in the optic nerve. Free radicals scavengers, superoxide dismutase plus catalase or dimethylthiourea were able to counteract the drop of phosphate metabolites in the peri-occlusive area. These results show that hypoxia leads to oxygen-derived free radical generation which can be responsible for cell damage and emphasize the role of free radicals in the pathogenesis of ocular diseases related to vascular dysfunction. PMID- 1587151 TI - Primary sclerosing cholangitis. AB - Primary sclerosing cholangitis is a condition of unknown cause. It is recognized by liver dysfunction and its characteristic radiologic appearance, which is related to portal tract inflammation, bile duct proliferation, and periductal fibroses involving small intrahepatic and large extrahepatic ducts. The disease lasts about 10 years from the time of diagnosis. Primary sclerosing cholangitis is recognized by abnormal results on routine liver function tests or by the development of clinical jaundice. An autoimmune cause has been suggested because of its strong association with inflammatory bowel disease, certain antigens, AIDS, and immunoregulatory abnormalities. Results of medical management of sclerosing cholangitis have been disappointing. Immunosuppressive drugs, copper chelating agents, and antibiotics have failed to alter progression of the disease. Colectomy in patients with inflammatory bowel disease also has no influence. The judicious use of dilations of strictures, bypass procedures, or resection can palliate jaundice in patients with primary sclerosing cholangitis, but liver transplantation is the definitive treatment. Because palliative operations increase the hazards of liver transplantation, percutaneous dilations and stentings are preferred initially. Cirrhosis and portal hypertension are indications for transplantation. In the future, transplantation may be indicated earlier in the course of the disease. PMID- 1587152 TI - Anterior surgery for the treatment of soft cervical disc herniation. AB - The authors present the results obtained in a series of 57 cases of soft cervical disc herniation submitted to anterior surgery. The cases included 52 radiculopathies and 5 myeloradiculopathies. Among the radiculopathies, 20 cases were treated by discectomy without magnification, and interbody fusion, and 32 by radical microdiscectomy, completed with interbody fusion in 19 cases and without fusion in 13. The 5 cases of myeloradiculopathy were all treated by microdiscectomy, with fusion in 2 cases and without fusion in 3. The results of treatment of the radiculopathies were evaluated as excellent or good in 80% of the cases treated by "macro" technique, and in 84% of those treated with "micro" technique; in the latter cases, more rapid and complete regression of pain, were always observed probably due to the more radical neurological compression obtained. The 5 cases of myeloradiculopathy obtained excellent results, with evident sensory and motor recovery. Long-term results for cases treated with or without fusion did not differ; the complications observed in the entire series may all be related to use of interbody grafting. The authors conclude that the method of choice in the surgical treatment of soft cervical herniation, with radicular or myeloradicular compression, is radical anterior microdiscectomy without interbody fusion. PMID- 1587153 TI - Indications and results of surgical treatment of cervical disc disease by anterior and posterior approach. AB - The authors report their experience with indications (130 cases) for the treatment of cervical disc disorders, which has recently witnessed an increase in cervicobrachial pain in disc-spinal cord conflict syndromes. After a first period during which the use of hemilanimoarthrectomy prevailed, there has been an evident increase in the number of cases treated by discectomy by Cloward fusion and an anterior approach. Thus, the results obtained in local symptoms have improved; more precisely, the problem of neck pain and cervical mobility have been resolved, while positive results in peripheral symptoms have remained the same. PMID- 1587154 TI - Silvio Zanoli. PMID- 1587155 TI - The diagnosis of lumbar stenosis. AB - The diagnosis of stenosis of the lumbar spinal canal is essentially based on clinical and radiographic examination. While clinical signs of involvement of the bone structure are few, neurological ones, however aspecific, may be detected (pluriradicular irritation, neurogenic claudication). Neurological instrumental tests (EMG, evoked potentials, etc.) are not of considerable aid to diagnosis. Radiographic examination, CT and MRI, are essential to prognosis and therapy. PMID- 1587156 TI - Radiology of the stenotic lumbar canal. AB - The main objective of imaging diagnostics in the study of the stenotic lumbar canal is that of revealing the presence of any contents/container conflict, of determining its site, extent, extension and, when possible, its etiopathogenesis. At present, CT and MRI constitute the most sensitive and specific methods, available necessarily preceded by a conventional radiological examination. Clinical assessment influences the choice of the method to use, whether alone or in association with others, as well as the method used to carry out the investigation; if we add all of this to correct technical execution, the radiological examination will provide a considerable amount of data. PMID- 1587157 TI - Lumbar stenosis surgery: the experience of the orthopaedic surgeon. AB - Between 1974 and 1989 350 patients were submitted to surgery for the treatment of stenosis of the lumbar canal; in 280 of these cases a minimum two-year follow-up was obtained. In all of the cases there was significant stenosis of the spinal canal, which was furthermore secondary to hypertrophy of the facet joints of degenerative nature. In 67% of the cases neurogenic claudication was present; in 57% there was monolateral radiculopathy, in 43% bilateral radiculopathy. The lesions extended from L4 to S1 in 39.2% of the cases, L3 to S1 in 36.3%, L5 to S1 in 8.5%, L2 to S1 in 7.2%, L4 to L5 in 4.6%, and L3 to L4 in 2.1%. Radiological diagnosis was confirmed by myelography and CT scan. Surgery involved laminectomy leaving intact at least 6 mm of the posterior facet joints in order to avoid destabilizing the spine; moreover, the anteromedial portion of the joint osteophytes was removed in order to release the lateral recess and, when necessary, decompression was extended to the intervertebral foramen. During the first years of our experience fusion of the posterior joints with osteosynthesis using plates and pedicular screws was associated with decompression in 43% of the cases. Thereafter, fusion was performed in only 17% of the cases. From a subjective point of view the results obtained in radiculopathies were satisfactory in only 87% of the cases, objectively in 72%. The results obtained with treatment of lumbar pain was better in patients in whom lumbosacral fusion was associated as compared to cases treated with laminectomy alone (85% vs. 65%). Complications were rare and mild. PMID- 1587158 TI - Lumbar stenosis surgery: the experience of the neurosurgeon. AB - Even when multiple levels are affected, lumbar canal stenosis can be surgically treated using the microsurgical technique. This microapproach combines the advantage of an efficient decompression of the compromised neurostructures along with the preservation of the spinous processes the interspinous ligaments, the medial section of the yellow ligament as well as of the biomechanically relevant portion of the facet joints. Thus, due to minimal surgical trauma spinal stability is maintained, resulting in reduction of postoperative discomfort and a favorable clinical outcome. We report the results of 35 patients operated on consecutively using the microsurgical technique. Our study further shows that there is a remarkable discrepancy between radiological and clinical evidence of the levels of stenosis. PMID- 1587159 TI - Degenerative spondylolisthesis: lumbar stenosis and instability. AB - Degenerative spondylolisthesis may manifest itself with different clinical pictures depending on the phase of the spondylotic disease. Based on pathophysiological criteria 24 patients affected with degenerative spondylolisthesis were divided into three groups: group I: those with spondylotic instability; group II: those with lumbar stenosis and current or potential segmental instability; group III: those with lumbar stenosis and naturally stabilized spondylolisthesis. Group I was treated by posterolateral fusion; group II by laminectomy, removal of the medial portion of the facets and posterolateral fusion; group III by laminectomy and removal of the medial portion of the facets. Long-term results were positive in 100% of the cases in group I, 90% in group II and 83% in group III, with no statistically significant differences between groups, because of the limited series of cases. The authors conclude that surgery for the treatment of degenerative spondylolisthesis must be based on age, symptoms, and the phase of the disease, and that when these indications suited to the clinical-radiographic picture are taken into account, good results may be obtained with different operations. PMID- 1587160 TI - Diagnosis, surgical indications and treatment of lumbar stenosis. AB - A diagnosis of vertebral lumbar stenosis is based on clinical and instrumental data derived from radiographic studies, CT scan, magnetic resonance, and myelography. Indications are based on an overall evaluation of clinical and instrumental data, in the search for a precise correlation between neurological symptoms and images. Conservative treatment includes medical and physical therapy, and use of a brace. Problems related to surgical treatment substantially consist in how many levels to open and how far to laterally release the nervous structures. PMID- 1587161 TI - Lumbar stenosis surgery: "recalibrage" according to Senegas. AB - In the treatment of lumbar stenosis the method known as "recalibrage" proposed by Senegas is the most recent alternative to extended traditional laminectomy. Posterior decompression, which is obtained by removal of the cephalic half of the laminae, the yellow ligaments and the intraforaminal part of the facet joint, reduces the risk of postsurgical instability and makes it possible to proceed with fusion which is not just posterolateral. In cases where there is intersegmental instability we applied the Hartshill rectangle, proposed by Doce, stabilized to the residual laminar and associated with genous grafting. Our experience is based on 48 cases treated with this method over the last three years. In 19 cases Hartshill fixation was used to complete "recalibrage". Results are generally satisfactory, although follow-up is short. The "relative gain" method proposed by Lassale and Garcon was used for evaluation. PMID- 1587162 TI - Stenosis of the nerve root canal caused by disc resorption. AB - Stenosis of the nerve root canal caused by isolated resorption of a lumbar disc is a frequently observed pathology, but one about which the orthopaedist still knows relatively little. Henry Crock was the first to reveal its principal pathogenetic factor, disc resorption, and to accurately describe the syndrome and its surgical treatment. A total of 22 patients operated according to Henry Crock's indications and followed-up after 2 years were reviewed. In 20 cases decompression alone was performed, while in 2 cases anterior fusion and MOSS instrumentation were associated. Of the 22 patients submitted to decompression 17 revealed complete regression of pain. Three cases failed: 1 patient had previously been treated with chymopapain, while 3 are awaiting anterior fusion to treat persistent lumbar pain. Follow-up is not sufficient for the two patients submitted to anterior fusion. PMID- 1587163 TI - Complications in the surgical treatment of lumbar stenosis. AB - The authors analyze the complications which may occur in the surgical treatment of lumbar stenosis. They report 4 cases of cauda equina syndrome and 8 dural tears in 96 patients aged from 21 to 81 years submitted to multiple bilateral laminectomy. Based on a review of the patients some considerations on surgery for the treatment of lumbar stenosis are discussed. The advanced age of the patients, hypertension, diabetes, vasculopathies in general, severe neurological deficit dating back some time contraindicate surgery. When surgery is indicated a correct preoperative evaluation by MRI from T12 to the sacrum is required to determine the extent of the laminectomy and a safe and accurate intra- and postoperative bleeding control is mandatory. Dural laceration may be repaired by a thoracolumbar fascia patch. PMID- 1587164 TI - Classification and pathomorphology of lumbar stenosis. AB - A classification system based on pathologic anatomy distinguishing between three types of lumbar stenosis is reported: stenosis of the spinal canal, isolated stenosis of the nerve root canal, and stenosis of the intervertebral foramen. Each type of stenosis is classified as primary, secondary, combined or mixed. Pathomorphological pictures which may represent the vertebral bodies, the neural arch and the discoligamentous structures in the various forms of stenosis, among which degenerative spondylolisthesis, are examined. Finally, the authors describe the pathologic modifications occurring in the nervous structures as the possible consequence of a lumbar stenosis. PMID- 1587165 TI - Anterior surgery of the upper cervical spine. AB - The authors report the results obtained in a series of more than 80 cases submitted to 76 operations of the upper cervical spine by transoral approach with a minimum follow-up of two years. The cases include: 15 unstable fractures or non union of the odontoid processes; 28 cases of post-traumatic instability of C1-C2 level without fracture of the odontoid process; 13 cases of rheumatoid arthritis with instability at C1-C2; 14 cases of severe anomalies of the craniovertebral junction, often associated with basilar impression and spinal cord compression, of which 7 cases presented with tetraparesis; 6 malignant tumors. The method used involves an anterior transoral approach, more often without tracheotomy, and with exposure of the anterior aspect of the atlas and of the odontoid process by means of a midline incision of the posterior wall of the pharynx. When spinal cord lesion was present, decompression and reconstruction by bone grafts taken from the iliac crest were performed. In nearly all of the cases osteosynthesis with an anterior plate was used. Complications were mild. There were two cases of infection, observed at the onset of our experience, which were resolved after removal of the instrumentation. There was loosening of a screw in three cases; this was eliminated through the digestive tube with no consequences. There were no early intra- or postoperative deaths. Consolidation was obtained in most of the patients, and only in three cases did we observe a loss of postoperative reduction. Among patients affected with tetraparesis we observed many cases of neurological recovery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587166 TI - Anterior surgery of the lower cervical spine. AB - The authors discuss the advantages and the limits of using an anterior approach to lower cervical spine; indications, surgical access, the use of bone graft for stabilization, and postoperative treatment are described. Based on their experience, the authors believe the Cloward method, involving decompression fusion by autologous cylindrical dowel bone graft, to be an ideal method in the treatment of cases of soft central disc hernia, hard hernia, the outcome of progressive instability, and in inflammatory and neo-plastic lesions of the vertebral body. PMID- 1587167 TI - The trapezial plate osteosynthesis: an advanced technology for anterior internal stabilization in cervical spine injuries and for the treatment of neck instability due to non traumatic causes. AB - The authors present a series of anterior fusion of the cervical spine using internal fixation by means of a screwed plate. After the description of the surgical technique utilized in 408 consecutive surgical procedures the authors report the results of 60 patients affected by traumatic lesions and followed up 1 to 3 years. In 27 cases a single-level fusion was performed; in 2 cases a two level fusion; in 17 cases a subtotal corporectomy, and in 14 cases a total corporectomy. A good bony fusion was obtained in all 60 cases. All patients improved neurologically from incomplete cord and root lesions. None of the patients showed neurological worsening. Complications were rare and minor. Anterior fusion of the cervical spine with an osteosynthetic screwed plate is a surgical technique that is able to offer satisfying outcomes in cervical traumatic lesions and in non traumatic cervical pathology. PMID- 1587168 TI - Colonoscopic screening for neoplasms in asymptomatic first-degree relatives of colon cancer patients. A controlled, prospective study. AB - Individuals with a family history of colorectal cancer are believed to be at an increased risk of developing colorectal neoplasia. To estimate this risk and the potential yield of screening colonoscopy in this population, we recruited and prospectively colonoscoped 181 asymptomatic first-degree relatives (FDR) of colorectal cancer patients and 83 asymptomatic controls (without a family history of colorectal cancer). The mean ages for the FDR and control groups were 48.2 +/- 12.5 and 54.8 +/- 11.0, respectively. Adenomatous polyps were detected in 14.4 percent of FDRs and 8.4 percent of controls. Although 92 percent of our FDRs had only one FDR afflicted with colon cancer, those subjects with two or more afflicted FDRs had an even higher risk of developing colonic adenomas (23.8 percent) than those with only one afflicted FDR (13.1 percent). A greater proportion of adenomas was found to be beyond the reach of flexible sigmoidoscopy in the FDR group than in the controls (48 percent vs. 25 percent, respectively). Logistic regression analysis revealed that age, male sex, and FDR status were independent risk factors for the presence of colonic adenomatous polyps (RR = 2.32, 2.86, and 3.49, respectively; P less than 0.001). Those at greatest risk for harboring an asymptomatic colonic adenoma are male FDRs over the age of 50 (40 percent vs. 20 percent for age-matched male controls). Based on probability curves, males with one FDR afflicted with colon cancer appear to have an increased risk of developing a colonic adenoma beginning at 40 years of age. Our results document, for the first time, an increased prevalence of colonoscopically detectable adenomas in asymptomatic first-degree relatives of colon cancer patients, as compared with asymptomatic controls, and support the use of colonoscopy as a routine screening tool in this high-risk group. PMID- 1587169 TI - Anal sphincter biofeedback relaxation treatment for women with intractable constipation symptoms. AB - Some constipated women have difficulty relaxing the striated muscles of the anal sphincters, sometimes called anismus. This study was developed to provide a biofeedback-based relaxation treatment to teach these patients to relax the "voluntary" anal sphincter muscle in order to assess whether this treatment would be effective in reducing symptomatology. Seven constipated patients who were unresponsive to a high-fiber diet and required persistent laxative dosing to achieve regular bowel frequency were studied. A dual-therapy approach, in which patients were taught to relax the anal sphincter muscles via biofeedback from a manometric anal sphincter probe, was used. Concurrently, patients were instructed in general biofeedback-relaxation techniques. All were treated as outpatients. Complete data were collected on five patients, one patient discontinued therapy, and one patient moved after treatment was completed. Stool frequency improved from a mean of 1.9 per week to a mean of 4.9 per week in six patients (P less than 0.05). In the five patients who completed the entire protocol, pain and bloating symptom levels were compared before and after treatment. Abdominal pain grade was reduced from 12.8 per week to a mean of 4.4 per week (P less than 0.05), and bloating was reduced from a mean of 14.3 per week to a mean of 6.0 per week (P less than 0.06). Follow-up of 2 to 4.5 years posttherapy showed continued improvement in bowel function and abdominal symptomatology. This treatment appears to be effective in improving stool frequency and in reducing the associated abdominal pain and bloating symptoms in constipated women with anismus. PMID- 1587170 TI - Challenging the predictive accuracy of Goodsall's rule for anal fistulas. AB - To examine the predictive accuracy of Goodsall's rule, the records of 216 patients (155 men and 61 women) who underwent surgery for complete submuscular anal fistulas from 1982 to 1989 were retrospectively reviewed. In accordance with Goodsall's rule, 90 percent of 124 patients with an external opening posterior to the transverse anal line had anal fistulas tracking to the midline (87 percent men and 97 percent women). Only 49 percent of the 92 patients with an external opening anterior to the transverse anal line had anal fistulas that tracked in the radial fashion predicted by Goodsall (57 percent men and 31 percent women). Instead, 71 percent of these patients (62 percent men and 90 percent women) had anterior fistulas tracking to the midline. Overall, 81 percent (77 percent men and 93 percent women) of patients had complete submuscular anal fistulas that coursed to the midline (51 percent midline posterior and 30 percent midline anterior). In summary, Goodsall's rule is accurate only when applied to complete submuscular anal fistulas with posterior external anal openings. The rule is inaccurate in describing the course of complete submuscular anal fistulas with an anterior external opening. The men in this group had anal fistulas that defied Goodsall's rule in an unpredictable manner, whereas 90 percent of the women had fistulas tracking to a midline anterior origin. PMID- 1587171 TI - Epidemiologic characteristics of the flat adenoma of Muto. A prospective study. AB - The flat adenoma is an endoscopically visible lesion that histologically consists of adenomatous change near the luminal surface of colonic tubules. We have described three families with hereditary colon cancer with later age of onset than familial adenomatous polyposis (FAP) and with multiple proximal colonic flat adenomas. These families have been linked to the FAP locus on chromosome 5. Our aim was to determine whether the flat adenoma is pathognomonic of this hereditary flat adenoma syndrome (HFAS) or merely an atypical or early tubular adenoma with occurrence in patients other than those from colon cancer-prone families. METHODS: We prospectively examined a population referred for colonoscopy within a one-year period. During colonoscopy, flat adenomas were specifically sought and all lesions were removed endoscopically and evaluated histologically. Members of known hereditary colon cancer families were excluded. RESULTS: One hundred forty eight patients underwent colonoscopy (64 men and 84 women). Median age was 61 years. Fifty-seven patients had 157 polyps. One hundred thirty-six polyps were reviewed histologically. Thirty-five (23.6 percent) of the referred patients had adenomas, of whom twelve patients had only flat adenomas while six had both flat and other adenomas (18 = 12 percent of 148). The associations between flat adenoma occurrence and various predictors (sex, race, prior colonic neoplasms, family history of cancer, synchronous adenomas) were similar to those seen with other adenomas. Flat adenomas were found in nearly equal proportions of patients under or over age 61 years (11 percent and 13 percent, respectively). Other adenomas were significantly more common in the older group (6 percent vs. 25 percent; P less than 0.002 by Fisher's exact test). CONCLUSION: In a referral practice, the flat adenoma has the same prevalence and associated risk factors as other adenomas, except for younger age of onset. Our data suggest that the flat adenoma represents an early stage of adenoma development that is manifested in a subset of patients from the general population and that, as an isolated event, does not provide a marker for a hereditary colon cancer-prone syndrome. PMID- 1587172 TI - Pouchogram: predictor of clinical outcome following ileal pouch-anal anastomosis. AB - Among 914 patients undergoing ileal pouch-anal anastomosis (IPAA) between January 1981 and June 1989, 463 (51 percent) had a pouchogram (meglumine diatrizoate [Gastrografin; E.R. Squibb & Sons, Inc., Princeton, NJ] enema) to assess anastomosis and ileal pouch integrity before closure of the ileostomy. The aim was to determine whether a pouchogram was useful in predicting clinical outcome. RESULTS: Abnormal findings were present in 74 patients (16 percent). These included anastomotic and pouch leaks and anstomotic strictures. Pouchograms were normal in the remaining 389 patients (84 percent). The incidence of significant anastomotic stricturing requiring dilatation under anesthesia was much higher in the abnormal than in the normal pouchogram group (33 percent vs. 4 percent, respectively; P less than 0.001). More significantly, an abnormal pouchogram was associated with an overall long-term failure rate of 23 percent, compared with 6 percent for a normal pouchogram (P less than 0.001). CONCLUSION: Abnormal findings in a pouchogram prior to ileostomy closure indicated those patients at high risk of long-term complications following IPAA. PMID- 1587173 TI - Sensory nerve endings in the puborectalis and anal region of the fetus and newborn. AB - The study was carried out in seven fetuses (ovulation ages were 16, 18, 20, 22, 26, 28, and 31 weeks, respectively) and in five full-term newborn babies. The modified Bielschowsky method and Barker's block silver impregnation were used. It was found that the muscle spindle was arranged in the puborectalis and the external sphincter muscles from the 20th week onward; the tendon organ was located in association with the musculo-tendinous junction of the puborectalis from the 20th week onward; the Pacinian corpuscle lay in the plane of cleavage between the internal anal sphincter and the external anal sphincter from the 22nd week onward, and in the presacral space from the 28th week onward, and the later lagged behind the former in development; the globular endings lay in the presacral space from the 28th week onward; and the free nerve ending was distributed in the epithelium of the anal mucosa and the epidermis around the anus from the 31st week onward. These sensory nerve endings tend to mature gradually with increasing age. It was concluded that these endings may be responsible for the reflex of the external anal sphincter and the anal sensation. PMID- 1587174 TI - New treatment of ulcerative colitis with K-76. AB - The complement inhibitor K-76 (Otsuka Pharmaceutical Co., Osaka, Japan) was clinically evaluated as a new drug for treatment of active stage ulcerative colitis (UC). As monotherapy, K-76 proved effective in four of five cases. Furthermore, in patients with active stage UC that continued despite administration of corticosteroid hormone and salicylazosulphapyridine (so-called refractory UC), concomitant administration of K-76 was effective in seven of 21 cases. Thus, we believe that the multifunctional agent K-76 will provide clinicians with a new therapeutic approach to inflammatory bowel diseases, including UC and Crohn's disease. PMID- 1587175 TI - Endoscopic enhancement of the healing of high-risk colon anastomoses by low-power helium-neon laser. An experimental study. AB - Recent studies suggest that helium-neon (He-Ne) lasers at low energy can enhance wound healing in intestinal anastomoses. In this experimental study, we tested the strength and collagen concentration of high-risk anastomoses of the rat colon after endoscopic irradiation by helium-neon laser. Our results show that repeated helium-neon laser irradiation (1.9 J/cm2) increases the bursting strength of the anastomoses by almost 100% on the fourth postoperative day. This effect is not observed by increasing the radiation dose (6.4 J/cm2). Differences in collagen (hydroxyproline) concentration did not reach statistical significance. PMID- 1587176 TI - Results of abdominoperineal resections for failures after combination chemotherapy and radiation therapy for anal canal cancers. AB - Thirty patients treated with combination chemotherapy (CT) and radiation therapy (RT) for anal canal carcinoma were reviewed retrospectively to analyze the results of abdominoperineal resection (APR) for treatment failures. Mean follow up was 34.9 months. Twenty-four patients had squamous carcinomas, and six had cloacogenic carcinomas. Twenty-five had negative inguinal lymph nodes, and five had positive inguinal lymph nodes. The group received 5-fluorouracil, mitomycin C, and 30 to 50 Gy of RT. Biopsy was obtained at six weeks posttherapy. Seventeen of 22 patients (77 percent) with primary tumors of less than 5 cm and negative nodes were disease free at 37 months post-CT-RT. None of the seven patients with primary tumors of greater than 5 cm or positive nodes were free of disease. APR was done for positive biopsy in eight patients and for local recurrence (disease detected after six months of treatment) in one patient. Eight of nine patients who had APR died of disease (mean, 20 months), and one of nine died of other causes. A review of published series, including our data, reveals 24 cases of APR post-CT-RT for positive biopsy, with 17 of 24 (71 percent) dead of disease within three years. APR for CT-RT failures has a poor prognosis. Future protocols may determine whether further CT-RT will improve survival. APR for palliation should always remain an option. PMID- 1587177 TI - Prognostic value of positive lymph nodes in rectal cancer. AB - Abdominal "curative" resections for rectal cancer in 109 patients with positive lymph nodes were prospectively studied. The best subdivision of patients for predicting outcome was into 1-3 and greater than 3 positive lymph node groups. Comparison with patients with greater than 3 positive lymph nodes demonstrated that patients with 1-3 positive nodes had less local (35.0 percent vs. 13.0 percent; P = 0.007) and less distant recurrence (45.0 percent vs. 26.0 percent; P = 0.04) and had much better crude five-year survival (58.2 percent vs. 17.0 percent; P less than 0.0001). For predicting postsurgical outcome in patients with positive lymph nodes, the results justify subdividing patients into the following two prognostic subgroups: 1) those with 1-3 involved lymph nodes and 2) those with metastatic tumor in four or more lymph nodes. PMID- 1587178 TI - One-stage restorative proctocolectomy without temporary defunctioning ileostomy. AB - A temporary ileostomy has been employed routinely by most medical centers to defunction the ileal reservoir after restorative proctocolectomy. The aim of this study was to compare the clinical outcome in patients who underwent restorative proctocolectomy with and without the use of a temporary, defunctioning ileostomy. A consecutive series of 58 patients was studied. Each patient underwent restorative proctocolectomy with quadruplicated ileal reservoir and stapled pouch anal anastomosis, without mucosectomy; 28 had a temporary, defunctioning ileostomy and 30 did not. The decision for or against an ileostomy was taken at the end of the operation. The two groups of patients were similar in age and sex distribution. There was no postoperative mortality. There were no significant differences in the incidence of pelvic sepsis, anastomotic stricture, and intestinal obstruction in patients without an ileostomy compared with patients with an ileostomy. The total length of stay in hospital after the operation was significantly reduced in the group of patients without an ileostomy (P less than 0.01). The avoidance of a temporary ileostomy did not lead to an increase in postoperative complications and was associated with a shorter length of stay in hospital after restorative proctocolectomy. PMID- 1587179 TI - Carcinoid tumors of Meckel's diverticula. Report of two cases and review of the literature. AB - Two cases of carcinoid tumors in Meckel's diverticula are reported. Additionally, data of 104 published cases of carcinoids in this rare location are analyzed. The average age of the patients is 56.6 years and corresponds to the age of patients with ileal carcinoids. Carcinoids in Meckel's diverticula also resemble ileal carcinoids in their biological behavior more than they do appendiceal carcinoids. Tumors larger than 5 mm have a marked risk to metastasize. By the time symptoms are present, 77 percent of these tumors have already metastasized. Men are affected by this tumor 2.5 times more often than women. Carcinoids in Meckel's diverticula metastasize twice as often in female as in male patients. More than 70 percent of carcinoids in Meckel's diverticula are found at the tips of the diverticula. An aggressive surgical management of tumors larger than 5 mm is recommended. PMID- 1587180 TI - Simplified balloon expulsion test. AB - The balloon expulsion test is a simple and inexpensive method to evaluate a patient's ability to expel and retain stool. In conjunction with other methods, it assists in identifying patients with outlet obstruction or incontinence. A simplified method of performing a balloon expulsion test is described. PMID- 1587181 TI - Bricker-Johnston sigmoid colon graft for repair of postradiation rectovaginal fistula and stricture performed with mechanical sutures. AB - In patients with postradiation rectovaginal fistula who are otherwise healthy and cured of their cancer, repair of the fistula with return to a normal lifestyle is indicated if this repair can be achieved with minimal morbidity, no mortality, and a good prospect for a functionally satisfactory result. The Bricker-Johnston vascular sigmoid colon graft fulfills these conditions by respecting the tissular equilibrium of the radiated rectum and supplying the area with a sound, vascular sigmoid pedicle graft. While this improves tissue vitality locally, it restores rectal function to a near-normal preradiation level and preserves the previously intact sphincter muscles. The concept of this repair is very sound, and its implementation is greatly facilitated technically by the use of mechanical suture instruments. In this presentation, we describe and show the use of stapling instruments in achieving a three-stage repair of a rectovaginal fistula with Bricker and Johnston's technique. PMID- 1587182 TI - Rare pelvic floor hernias. Report of a case and review of the literature. AB - The case of a 64-year-old female who presented with difficult evacuation of stool is reported. A posterior perineal hernia was diagnosed by dynamic proctography. The patient had an unusual herniation of the upper rectum through the perineal defect. At surgery, there was no peritoneal sac, since the herniation occurred extraperitoneally. The patient was treated with repair of the pelvic floor using Marlex mesh and rectopexy. Pelvic floor hernias are rare and often difficult to diagnose. The three types, in order of decreasing frequency, are obturator, perineal, and sciatic. The etiology, diagnosis, and treatment of each is discussed. PMID- 1587183 TI - Method to avoid colostomy soiling. PMID- 1587184 TI - Pneumatosis intestinalis in patients with Crohn's disease. AB - The prevalence, predictors, and significance of pneumatosis were determined in 50 patients with Crohn's disease who had abdominal CT scans to rule out abscess. The presence or absence of six CT descriptors and 17 clinical descriptors was documented. CT scans of a control group of 50 subjects without inflammatory bowel disease were also examined. Data was analyzed by two-sample t tests and Fisher's exact test. Pneumatosis was found in six of 50 patients with Crohn's disease and in none of the controls. Corticosteroid treatment was the single clinical variable relating significantly (P = 0.025) to pneumatosis, although trends toward absence of resection, short duration of illness, and more severe anemia were also evident in this group. This study suggests that the presence of pneumatosis alone does not dictate a specific course of treatment, but when pneumatosis is present, careful monitoring is required and therapy is based on the overall clinical picture. PMID- 1587185 TI - Tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6 expression in inflammatory bowel disease. AB - The etiology of ulcerative colitis (UC) and Crohn's disease (CD) remains enigmatic. Infiltrating intestinal macrophages are capable of producing the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and interleukin-6 (IL-6). We investigated the presence of IL-6, TNF-alpha and IL-1 beta mRNA transcripts in inflammatory bowel disease (IBD), normal, and other inflammatory intestinal specimens utilizing the polymerase chain reaction (PCR). TNF-alpha mRNA levels did not very between inflammatory bowel disease and control specimens. IL-1 beta mRNA levels were highest in active UC and noninflammatory bowel disease inflammatory specimens while IL-6 mRNA levels were highest in active IBD specimens. Infiltrating T cells, macrophages, and B cells were identified as sources of IL-6 protein in inflammatory bowel disease specimens by immunofluorescent staining. IL-6 transcripts were elevated only in active inflammatory bowel disease specimens, suggesting that IL-6 mediated immune processes are ongoing in the inflammatory mucosal environment of CD and UC. PMID- 1587186 TI - Effects of starvation and refeeding on jejunal disaccharidase activity. AB - In the rat, starvation lowers jejunal sucrase activity and increases or has no effect upon jejunal lactase activity. The mechanism by which starvation influences these intrinsic microvillus proteins remains unclear. Jejunal sucrase and lactase activities were studied during starvation or refeeding after a three day fast. Using polyclonal monospecific antibodies, sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH) protein contents were measured in parallel to determine changes in enzyme activation. Sucrase activity and SI protein fell after two and three days of fasting and rose during refeeding. In contrast, lactase activity and jejunal LPH content increased after starvation and decreased after refeeding for 48 hr. For both enzymes, changes in catalytic activity and protein content occurred in parallel. [3H]Leucine incorporation studies in vivo showed more labeling of immunoprecipitable LPH than SI during starvation, but refeeding induced relatively more labeling of SI than of LPH. Therefore, starvation and refeeding produce opposing effects upon jejunal lactase and sucrase activities by modulating LPH and SI protein production and not by modifying enzyme activation. PMID- 1587187 TI - Prolonged clearance is the primary abnormal reflux parameter in patients with progressive systemic sclerosis and esophagitis. AB - The purpose of this study is to determine if frequent reflux events from an incompetent LES or poor clearance from decreased peristalsis is the predominant abnormality in PSS patients with severe reflux esophagitis. Seven patients with both classic manometric findings of PSS and endoscopic findings of esophageal ulcerations and/or Barrett's esophagus were compared to nine patients with similar endoscopic findings but with no evidence of a connective tissue disorder. All patients underwent simultaneous intraesophageal pH monitoring and scintigraphy for a total of 40 min after a radiolabeled meal. Four of the PSS patients and all the non-PSS patients had simultaneous manometry. We found that PSS patients had significantly fewer reflux events (P less than 0.01), but the reflux events had significantly longer duration (P less than 0.01) compared to patients with similar severity of esophagitis and no connective tissue disease. We conclude that decreased smooth muscle peristalsis appears to be the primary contributor to acid exposure and esophageal injury in PSS. PMID- 1587188 TI - Meal-stimulated canine jejunal ionic absorption. Effect of direct jejunal meal delivery and premeal intravenous hydration. AB - The ingestion of a meal stimulates water and ion absorption from the small intestine. The administration of nutrient substances directly to the small bowel can cause dumping symptoms, with intraluminal fluid accumulation and relative systemic hypovolemia. This study compared the effect of oral versus direct jejunal meal delivery on jejunal water and ion absorption, with and without premeal intravenous saline infusion. Jejunal absorption studies (N = 40) were performed on dogs with 25 cm proximal jejunal Thiry-Vella fistulas and feeding jejunostomies. Luminal perfusion with [14C]PEG was used to calculate fluxes of water and electrolytes. Five groups were randomly studied: (1) intravenous 0.9% saline alone, (2) oral meal alone, (3) intravenous 0.9% saline plus oral meal, (4) jejunal meal alone, and (5) intravenous 0.9% saline plus jejunal meal. Hydration status was assessed hourly by measurement of hematocrit. Water and electrolyte absorption was significantly stimulated by both oral and jejunal meal delivery (P less than 0.01). Intravenous saline hydration significantly reduced the hematocrit (P less than 0.05) but did not alter the proabsorptive response to an oral or jejunal meal. In conclusion, a postprandial signal for proximal jejunal water and electrolyte absorption was stimulated equally by orally or jejunally administered nutrients and was not affected by premeal hydration. These data support the hypothesis that the proabsorptive signal that stimulates water and ion absorption is an enteroenteric phenomenon originating from the small intestine, without implicating pathophysiologic events such as hypovolemia or dumping. PMID- 1587189 TI - Normal 24-hr ambulatory esophageal pH values. Influence of study center, pH electrode, age, and gender. AB - Although the most sensitive and specific test for diagnosing gastroesophageal reflux disease, normal standards for prolonged esophageal pH monitoring are based on small sample sizes with questions raised about the effects of pH electrode, older age, gender, and methods of data analysis on pH variables. Recently three groups have established normal data bases using similar methodology. Multiple regression and nonparametric analyses showed that the values for the six traditional pH parameters were comparable across study centers. Therefore, the groups were combined for a total study population of 110 healthy subjects (47 men, 63 women, mean age 38 years with a range of 20-84 years). Further nonparametric analyses revealed the following: (1) type of pH electrode (antimony vs glass) is not significantly related to parameters of physiologic acid reflux; (2) age is not independently related to pH parameters; (3) men tend to have more physiologic reflux than women; and (4) older men tend to experience longer episodes of reflux than younger men and women. There was a significant effect of gender and a significant interaction between age and gender on the number of episodes greater than 5 min (P = 0.008). Nearly significant differences were found for percentage of total acid exposure time (P = 0.03), total reflux episodes (P = 0.02), and the longest reflux episode (P = 0.02). We believe these normal esophageal pH values can be used confidently as standards in any laboratory, and consideration should be given to developing separate standards for men and women. PMID- 1587190 TI - Prolonged intraesophageal pH monitoring with 16-hr overnight recording. Comparison with "24-hr" analysis. AB - From studies in 43 patients (17 male, 26 female, mean age 51 years), we compared the analysis of the routine complete "24-hr" ambulatory esophageal pH monitoring study to that of the 16-hr overnight interval (4:00 PM to 8:00 AM). The latter included a major meal with an upright postprandial period and a recumbent period. All patients were monitored for at least 20 hr (median = 22.6 hr). The percent distal esophageal pH less than 4.0 and number of reflux episodes were measured for the total, upright, and recumbent periods of both the 16-hr and "24-hr" monitoring times. Significant (P less than 0.001) positive correlations were found for all comparisons between the two monitoring periods including percent time of pH less than 4.0 (total: r = 0.98; upright: r = 0.96) and number of episodes (totals r = 0.97; upright: r = 0.93). Patients were separated into normal and abnormal refluxers based on results of "24-hr" monitoring (pH below 4.0 greater than 4.2% total time; greater than 6.0% upright; greater than 1.2% recumbent). Based on this, sensitivity and specificity for 16-hr monitoring were as follows: total study: 86% and 95%; upright: 80% and 91%; recumbent: 100% for both. CONCLUSIONS: (1) a 16-hr overnight pH monitoring period can provide a reliable representation of "24-hr" distal esophageal acid exposure, (2) this shorter monitoring may improve patient acceptability and compliance, and (3) the symptom index was changed in 26.3% of patients using the 16-hr evaluation. PMID- 1587191 TI - Nizatidine versus placebo in gastroesophageal reflux disease. A six-week, multicenter, randomized, double-blind comparison. Nizatidine Gastroesophageal Reflux Disease Study Group. AB - In a randomized, multicenter trial, nizatidine 150 mg or 300 mg, or placebo, was administered twice daily for six weeks to 515 patients with gastroesophageal reflux disease (GERD). Gelusil antacid tablets were taken as needed for pain. Significantly superior rates of endoscopically proven complete healing (normal appearing mucosa) versus placebo occurred after three weeks with nizatidine 150 mg, and after six weeks with nizatidine 300 mg. Six-week healing rates were 38.5% for nizatidine 300 mg, 41.1% for nizatidine 150 mg, and 25.8% for placebo. The nizatidine 150 mg treatment group had significantly greater improvement in daytime and nighttime heartburn severity after one day of therapy versus placebo. Twice-daily administration of nizatidine 150 mg or 300 mg provides prompt relief from the major symptom of GERD, heartburn, and complete healing of esophagitis is seen in many patients. PMID- 1587192 TI - Vicryl-scarf-induced scarring around esophagogastric junction as treatment of esophageal reflux disease. An experimental study in the dog. AB - A ringlike structure around the cardia has proven to be sufficient in preventing gastroesophageal reflux, as seen with the Angelchick prosthesis. To avoid the insertion of a nonabsorbable foreign body, a scarring was induced by implanting a Vicryl scarf around the esophagogastric junction. Reflux disease was induced in 18 dogs by circular cardiomyomectomy. In 12 dogs, a Vicryl scarf was laid around the cardia; six dogs served as controls. All of the dogs in the control group either died or had to be sacrificed due to severe reflux esophagitis. All animals receiving the scarf survived the entire duration of the experiment. Endoscopically, only one case of temporary reflux esophagitis could be detected. Long-term pH-metry demonstrated complete reflux suppression after the third postoperative month. Radiographically, esophagogastric transit was always unimpaired. On autopsy, the scarf was found to have changed into a slim scarring after the sixth postoperative month and then remained unaltered. We conclude that inducing scarring around the cardia is as effective in reflux prevention as the silicone ring. PMID- 1587193 TI - Effect of omeprazole on gastric first-pass metabolism of ethanol. AB - Some commonly used H2-receptor antagonists affect gastric first-pass metabolism of ethanol and lead to unexpectedly high blood alcohol concentrations after consumption of alcohol. To investigate whether omeprazole--a substituted benzimidazole recently approved for clinical use--has a similar harmful effect, we administered a moderate dose of ethanol (0.3 g/kg body wt) orally to seven normal volunteers before and after one week of omeprazole administration (20 mg daily). No significant effect of the drug was found on either mean peak blood alcohol concentrations or on areas under the blood alcohol curve; neither did these parameters differ significantly before or after an acute dose of omeprazole (13.2 mg/kg body wt) in rats, whether ethanol (0.25 g/kg body wt) was administered intragastrically or intravenously. In vitro, omeprazole in concentrations likely to occur in the gastric lumen (0.01-1.0 mM), did not affect gastric alcohol dehydrogenase activity of humans or rats. Thus omeprazole does not affect gastric first-pass metabolism of ethanol and can be considered as a safe choice for the treatment of patients who do not refrain from alcohol consumption during therapy. PMID- 1587194 TI - Comparison of omeprazole and ranitidine in treatment of refractory gastroesophageal reflux disease in patients with gastric acid hypersecretion. AB - Secretion of gastric acid and volume, serum gastrin concentration, and ambulatory 24-hr esophageal pH monitoring were evaluated prospectively in 12 patients with idiopathic gastric acid hypersecretion (basal acid output greater than 10.0 meq/hr) undergoing treatment for refractory chronic long-standing pyrosis. Treatment lasted six months and consisted of three months of ranitidine (mean 2150 mg/day, range 1200-3000 mg/day), followed by three months of omeprazole (mean 33 mg/day, range 20-60 mg/day). Both ranitidine and omeprazole significantly reduced gastric acid output (P less than 0.001) and gastric volume output (P less than 0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis. Total reflux time (percent 24 hr intraesophageal pH less than 4) was significantly reduced by ranitidine (P less than 0.02) and omeprazole (P less than 0.001) compared to basal evaluation; however, the effects of omeprazole were significantly greater than ranitidine (P less than 0.05). Omeprazole caused a significant increase in serum gastrin concentration compared to both basal and ranitidine (P less than 0.05). Endoscopically documented erosive esophagitis was present in nine of the 12 patients, and seven of the 12 patients had Barrett's epithelium. All 12 patients had complete resolution of pyrosis and healed esophagitis by six months, but no significant endoscopic regression was observed in the extent of Barrett's epithelium. No side effects occurred with these high doses of ranitidine or omeprazole. These results indicate that high-dose ranitidine and omeprazole are effective therapy for refractory gastroesophageal reflux disease. However, with omeprazole, total reflux times are reduced more than with ranitidine, often into the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587195 TI - Paradoxical response to cerulein on sphincter of Oddi in the patient with gastrectomy. AB - Sphincter of Oddi motility was measured in 55 gallstone patients either through the sinus tract of percutaneous transhepatic biliary drainage or through the T tube. The influence of cholecystectomy and gastrectomy on the sphincter of Oddi was analyzed by comparing responses in patients with or without surgery to the administration of cerulein and the ingestion of dry egg yolk. When comparing cholecystectomized patients to nonsurgical subjects, cholecystectomy revealed no influence on the response to cerulein and feeding. Both groups showed relaxation of contraction waves after provocations. On the other hand, two thirds of the postgastrectomy patients showed an acceleration in the contractions of the sphincter of Oddi after provocations (one third showed no change), while all of the nongastrectomy group saw the disappearance of the wave after cerulein administration and 83% revealed complete suppression of the wave after feeding. It is suspected that this paradoxical response to CCK on the sphincter of Oddi is a lithogenic factor after gastrectomy. PMID- 1587196 TI - Risk factors for gallstone formation during rapid loss of weight. AB - Risk factors for the development of gallstones during rapid weight loss were assessed in 457 subjects who entered a weight control program (520 kcal/day). Absence of gallstones in these subjects was documented by ultrasonography prior to entry into the study. Ultrasonography was performed again at 16 weeks on the subjects who remained in the study (N = 248). The incidence of gallstones by 16 weeks of rapid weight loss was 10.9% (27/248). Most factors associated with gallstones in the general population, eg, older age, female gender, parity, positive family history, etc, were not associated with gallstones in this population. The risk factors for developing gallstones included increased initial body mass index [weight (kg)/height (m)2], amount of body mass index loss, and serum triglyceride levels. The positive predictive value of these risk factors was 75%, but the sensitivity was only 12%. These observations indicate that risk factors for the development of gallstones during rapid weight loss are probably different from those in the general population. The factors identified by this study are useful in predicting patients at high risk for gallstones. However, since only a minority of gallstones that form can be predicted, further study is needed to identify additional factors that will improve our ability to predict gallstone formation. PMID- 1587197 TI - Effect of verapamil on human intestinal transit. AB - Although constipation is a well-known side effect of calcium channel blockers such as verapamil, this side effect has not been evaluated in a quantitative manner. In a double-blind, randomized, crossover trial, the effect of verapamil (240 mg/day) was compared to placebo in 15 normal male volunteers. Subjects recorded their bowel movements and any side effects. Scintigraphy was used to quantitate gastric emptying, small intestinal transit, and colonic transit. In the study period of four days, verapamil did not change the frequency, consistency, or passage of bowel movements. A significantly increased number of side effects was noted during verapamil treatment--notably abdominal pain and dry mouth. The slope of gastric emptying was not significantly different for verapamil (0.012 +/- 0.02) than for placebo (0.013 +/- 0.001). Distal ileum filling was also not different for verapamil (0.41 +/- 0.13%/min) than placebo (0.33 +/- 0.05%/min). Progression of the colonic geometric center was significantly delayed at 48 hr by verapamil (5.2 +/- 0.4 vs 6.2 +/- 0.23; P less than 0.01). This study suggests that the constipating effect of verapamil is due to a delay of colonic transit and not due to an effect on upper gastrointestinal transit. PMID- 1587198 TI - Changes in mesenteric venous flow due to celiac sprue. AB - Villus atrophy in celiac sprue determines not only a great reduction of the intestinal absorptive surface, but also destroys the underlying microcirculation which depends on the small artery of the villus and the rich network of capillaries. This may result in a significant shortening of the mesenteric vascular bed. We describe three cases of celiac sprue in which duplex Doppler ultrasound flowmetry revealed a high blood flow velocity in the superior mesenteric vein during the acute stage of the disease. A gluten withdrawal diet produced in all cases a restoration of the normal thickness of the mucosa, together with a significant decrease of blood flow velocity in the superior mesenteric vein. PMID- 1587199 TI - Treatment of severe steatorrhea with ox bile in an ileectomy patient with residual colon. AB - Patients with ileectomy can present with severe steatorrhea due to bile acid depletion. While exogenous bile acid would seem to be ideal therapy for this condition, it is not often used because it is thought that the bile acid would be malabsorbed and would enter the colon, producing a secretory diarrhea. This report describes a patient who had an ileectomy and partial right colon resection for Crohn's disease and then developed severe steatorrhea due to bile acid malabsorption. Although steatorrhea was reduced from 134 to 9 g/24 hr with chronic ingestion of ox bile extract, stool weight did not increase with ox bile (stool weight 669 g/24 hr before therapy and 507 g/24 hr after therapy). In this patient, oral bile acid supplementation reduced fat excretion markedly, but did not aggravate diarrhea, even though the colon was still present. This result may have been due to impaired solubility of bile acid in fecal fluid due to an acid pH or to binding of bile acid with particles of solid stool. Ingestion of ox bile extract does not necessarily increase stool weight in patients with defective fat absorption due to bile acid malabsorption and can be tried with caution in an effort to diminish steatorrhea. PMID- 1587200 TI - Mantle zone lymphoma of the colon simulating diffuse inflammatory bowel disease. Role of immunohistochemistry in establishing the diagnosis. AB - We describe the first reported case of mantle zone lymphoma of the colon presenting as diffuse ileocolitis simulating severe inflammatory bowel disease. This case serves to illustrate the importance of immunohistochemistry in establishing the diagnosis of lymphoma in extranodal sites. PMID- 1587201 TI - Gastric pseudolymphoma. Not necessarily a benign lesion. AB - Gastric pseudolymphoma is thought to be a benign process. This report documents the malignant behavior of a gastric pseudolymphoma that was thought to be benign until a distant malignant B-cell lymphoma was demonstrated. Subsequent evaluation traced the B-cell lymphoma back to the gastric "pseudolymphoma." This finding stresses the relationship between gastric pseudolymphoma and gastric lymphoma, and the malignant potential of gastric pseudolymphoma. Multimodal tissue evaluation using histology, immunohistochemistry, and flow cytometry is essential. Surgical resection is the primary therapy for gastric pseudolymphoma. PMID- 1587202 TI - Neuroleptic malignant syndrome induced by domperidone. AB - A 47-year-old woman with diabetic gastroparesis, on treatment with domperidone, a dopamine-receptor antagonist, was admitted to the hospital in coma, with high blood pressure and nonreactive pupils. She then developed high fever. Her condition progressively worsened for two days, when muscle rigidity was noted and creatine phosphokinase was greater than 2000 U/liter. A diagnosis of neuroleptic malignant syndrome was made, and the patient was given dantrolene with prompt and complete resolution of all signs and symptoms. Subsequent inquiry revealed a distant past history of positive muscle biopsy for malignant hyperthermia, obtained after the diagnosis had been made in a family member. This case suggests that domperidone may induce neuroleptic malignant syndrome and that patients with malignant hyperthermia are at increased risk for this complication. PMID- 1587203 TI - Pneumatosis cystoides intestinalis in intestinal pseudoobstruction. Resolution after therapy with metronidazole. AB - A 66-year-old man with chronic idiopathic intestinal pseudoobstruction was admitted for pneumatosis cystoides intestinalis, complicated by pneumoperitoneum. The latter conditions resolved after treatment with metronidazole. There was no favorable effect of the prokinetic agents cisapride and erythromycin. To the authors' knowledge, this is the first reported case of successful treatment of pneumatosis cystoides intestinalis with metronidazole in primary chronic intestinal pseudoobstruction. PMID- 1587204 TI - Acute pancreatitis from intussusception of a gastric polyp in a patient with Gardner's syndrome. AB - Gastric polyps in Gardner's syndrome are usually benign small fundic gland neoplasms with little clinical significance. We report a case of gastroduodenal intussusception secondary to a large benign gastric polyp in a 44-year-old woman with Gardner's syndrome who presented with acute pancreatitis. The intussuscepted polyp caused obstruction of the ampulla of Vater with subsequent acute pancreatitis. PMID- 1587205 TI - Basal sphincter of Oddi pressure never elevated in alcoholic pancreatitis? PMID- 1587206 TI - Helicobacter pylori and gastritis. PMID- 1587207 TI - Polycythemia vera. AB - Polycythemia vera (PV) is one of the myeloproliferative diseases, and, as such, is an example of clonal hematopoiesis. The progeny of a single, abnormal, hematopoietic stem cell gain a growth advantage over their normal counterparts resulting in overproduction of red cells generally accompanied by overproduction of granulocytes and platelets as well. There are a variety of nonspecific symptoms at onset related to the increased red cell mass and hematocrit accompanied by the more specific manifestations of pruritus, erythromelalgia, and hepatic, portal, and mesenteric vein thrombosis. Splenomegaly and hypertension are common. The laboratory hallmark is an increased red cell mass. There is also often an increase in white cell count, platelet count, and leukocyte alkaline phosphatase along with other findings reflecting the increased rate of turnover of hematopoietic cells. The bone marrow biopsy generally displays hypercellularity involving all three cell lines and absent iron stores. The diagnosis of PV depends on excluding spurious polycythemia in which there is a high hematocrit but a normal red cell mass and secondary polycythemia in which there is an increased red cell mass in response to tissue hypoxia or the inappropriate production of erythropoietin, generally by a tumor. In addition, one should try to establish the diagnosis in a positive fashion by a combination of studies of the blood and bone marrow. Phlebotomy and occasionally plateletpheresis should be used as acute therapy. Chronic therapy is guided by the knowledge that patients treated with phlebotomy alone have an increased rate of thrombotic complications particularly in older patients and those with previous thrombotic disease. Myelosuppressive therapy can reduce the incidence of these complications, but is commonly associated with an increased incidence of second malignancies, particularly acute leukemia. At present, hydroxyurea is the myelosuppressive agent of choice. Antiplatelet agents have a limited role except in the palliation of the syndrome of erythromelalgia. Median survival is approximately 10 years. As implied above, the causes of morbidity and mortality vary with the mode of chronic therapy which has been employed, leukemia being more common after myelosuppressive therapy and thrombotic complications being more common after therapy with phlebotomy alone. Ten percent to 50% of patients move into a spent phase followed by postpolycythemic myeloid metaplasia, irrespective of previous therapy employed. Eventually, the major problems may be cytopenias and massive splenomegaly. PMID- 1587208 TI - [Lyme borreliosis in an endemic region in Europe. Prevalence of antibodies and clinical spectrum]. AB - A representative sample of the population of two villages located in an area of North Baden where borreliosis is endemic was studied to ascertain the prevalence of antibodies against Borrelia burgdorferi and of clinical abnormalities. The aim of the study was to determine what clinical symptoms and signs were correlated with positive antibody status. Out of the 2928 inhabitants 1228 were investigated, and 207 of these (16.9%) were seropositive. Certain clinical abnormalities showed highly significant statistical correlations with positive antibody status. Arthritis (defined in terms of heat, redness and effusion) was noted in 34.3% of the seropositive patients, but in only 9.3% of seronegative patients (P less than 0.0001). Complaints of arthralgia were noted in 23.4% of seropositive patients and 13.3% of seronegative patients (P less than 0.001). Motor neuropathies showed similar correlation with seropositive status (12.0% vs 4.0%; P less than 0.001), as did sensory neuropathies (25.4% vs 6.7%; P less than 0.001). Differences were also noted in the prevalence of cardiac arrhythmias (ventricular extrasystoles, conduction abnormalities and intermittent tachyarrhythmias), which were found in 19.8% of the seropositive as against 3.0% of the seronegative subjects (P less than 0.001). The findings are evidence of a causal link between the listed clinical abnormalities and the presence of antibodies against Borrelia burgdorferi. PMID- 1587209 TI - [Interstitial lupus nephritis]. AB - A 17-year old-male presented with a 6-week history of weight loss, lassitude and calf pains. On examination he was very pale. Laboratory tests showed a very high erythrocyte sedimentation rate (155 mm in the first hour), anaemia (haemoglobin 10.1 g/dl), and a raised serum creatinine of 1.54 mg/dl. Microhaematuria (5-10 erythrocytes/microliter) and pronounced pyuria (500 leucocytes/microliter) were present, but the urine was sterile and there was no increase in albumin excretion. The serum IgG was raised to 75.7 g/l, suggesting an autoimmune disorder. Anti-nuclear antibodies (titre 1 : 1920) and anti-double-stranded DNA antibodies (31 U/ml) were present, while the serum complement C4 was decreased to 0.11 g/l. Renal histology showed an interstitial nephritis without glomerular involvement, while the bone marrow showed vasculitis accompanied by a prominent plasma-cell infiltrate. A diagnosis of interstitial nephritis associated with systemic lupus erythematosus was made, with asymptomatic cardiac and hepatic involvement. Renal function recovered rapidly with prednisolone therapy (initial dose 2 mg/kg.d). While glomerulonephritis is the most common lupus-associated renal disorder, isolated interstitial nephritis may occur in some cases, often with an absence of proteinuria. PMID- 1587210 TI - [Electrocardiographic localization of infarct. A contribution to ECG nomenclature]. PMID- 1587211 TI - [Postprandial lipemia and arteriosclerosis]. PMID- 1587212 TI - [Inspection of patients' documents by the hospital administration]. PMID- 1587213 TI - [Cyclosporin in refractory atopic neurodermatitis]. PMID- 1587214 TI - [The effect of verapamil on left ventricular diastolic function in coronary heart disease]. AB - Echocardiography was performed on 21 patients (6 women, 15 men; mean age 52 [40 68] years) with coronary heart disease (at least 75% stenosis), before and after taking 80 or 120 mg verapamil, to test the drug's acute effect on left ventricular (LV) relaxation and filling. After taking 80 mg verapamil the only significant (P less than 0.05) decrease was in the proportion of isovolumetric relaxation time to cardiac cycle. The echocardiographic changes were significantly (P less than 0.01) greater after 120 mg than 80 mg: Isovolumetric relaxation time decreased by 13 and 4%, respectively, flow integral of early diastolic LV filling (E wave) increased by 17 and 2%, and atrial filling fraction (atrial component of LV filling) fell by 14 and 2%. Apparently verapamil has a positive effect on the energetically important early diastolic relaxation of the left ventricle. Thus diastolic abnormalities of LV function in patients with coronary heart disease are not fixed but can be at least partially improved with verapamil. PMID- 1587215 TI - [Primary pulmonary hypertension and mesangioproliferative glomerulonephritis in HIV infection]. AB - Four years after an HIV infection and without any preceding illness characteristic of AIDS, a 24-year-old woman developed dyspnoea on exertion and peripheral oedema. She had for several years been an intravenous drug addict and contracted hepatitis A and B. There were no symptoms of the HIV infection. Clinical, radiological and echocardiographic examination demonstrated right ventricular failure caused by pulmonary hypertension not due to pulmonary embolism or another known aetiology. The patient died suddenly 9 months after the diagnosis from heart failure. Autopsy established primary pulmonary hypertension with pathognomonic plexogenic pulmonary arterial disease which had led to cor pulmonale with overload myocarditis. Although there had been no clinical signs of renal failure, there was histological evidence of mesangioproliferative glomerulonephritis and non-destructive interstitial nephritis. This case demonstrates that, in addition to the typical AIDS-associated diseases, other rarer syndromes may, in uncertain ways but connected with the HIV infection, decide the prognosis of such patients. PMID- 1587216 TI - [Multiple myeloma with antinuclear antibodies. Its course during cytostatic therapy]. AB - A 56-year-old man complained of general malaise, diffuse bone pain, nocturnal sweating, lack of appetite and weight loss (7 kg within one year). Pain in the pelvic and lumbar regions markedly impaired movement. Roentgenologically, multiple lucencies were visualised in many skeletal areas. Examination of the bone marrow revealed an increase in the proportion of atypical plasma cells to 40%. The IgG concentration was 29.8 milligrams, mainly monoclonal immunoglobulins of the IgG-kappa type, which reacted against nuclear antigens (68-kD-U1-RNP nuclear protein) with a 1:2,000 titre. The symptoms markedly regressed under cyclical combined therapy with three times 5 mg melphalan daily for 4 days and 100 mg prednisolone daily for 7 days (a total of 24 cycles). At the same time the IgG concentration and the autoantibody titre decreased markedly and the patient became symptom-free. PMID- 1587217 TI - [Heart involvement in blunt thoracic trauma]. PMID- 1587218 TI - [Do we recognize type-II diabetes in timely fashion?]. PMID- 1587219 TI - [The treatment of nontuberculous mycobacterioses]. PMID- 1587220 TI - [Hemodilution plus heparinization in a regional cerebral infarct?]. PMID- 1587221 TI - [Long-term manometry in diffuse esophageal spasm]. PMID- 1587222 TI - [Serological screening for Helicobacter pylori. Can a blood test make gastroscopy superfluous?]. PMID- 1587223 TI - Lung function and the Hering Breuer reflex in the neonatal period. AB - Lung function and the occurrence of the Hering Breuer reflex during the neonatal period has been investigated. To assess the effect of extrauterine and intrauterine maturation on the strength of the reflex both preterm and term infants were recruited. Ten preterm infants, born at a median gestational age of 29.5 weeks (range 27-34) were studied serially over the first four weeks of life and 10 term infants were studied at a median postnatal age of 1.5 days (1-4). All of the infants were recruited from the neonatal unit and initially had had some form of respiratory distress. Respiratory rate, tidal volume and compliance were measured and end inspiratory occlusion performed in an attempt to provoke the Hering Breuer reflex. The Hering Breuer reflex was provoked in all infants on all occasions. There was no difference in the strength of the reflex between the preterm and term infants or preterm infants studied at different postnatal ages. All infants studied regardless of maturity or postnatal age had non-compliant lungs and a rapid respiratory rate. These data suggest a lack of intrauterine and extrauterine maturation of the Hering Breuer reflex in the neonatal period amongst infants with non-compliant lungs. PMID- 1587224 TI - The effect of intrauterine growth retardation on the quality of general movements in the human fetus. AB - The effect of severe intrauterine growth retardation on the quality of general movements was studied longitudinally in 17 human fetuses. During the prenatal and postnatal periods, fetal movements were recorded by means of weekly 1 h ultrasound and video registrations. Neurological examinations were performed at 1, 3, 6 and 12 months after birth. No clear effect of uncomplicated intrauterine growth retardation could be detected on the quality of general movements. General movements became slow and small in amplitude (4/5) in cases where there was a reduction in the amount of amniotic fluid. Parallel to the onset of abnormal fetal heart rate patterns, general movements became poor in repertoire (7/7), while they were hardly discernible after further deterioration of the fetal condition (5/7). With the exception of 3 infants with cerebral haemorrhages, the quality of general movements observed just before and after birth was identical (13/16). In these infants, the quality of general movements as well as the results of the standardized neurological examination tended to normalize at 3 months and 1 year, respectively. Uncomplicated IUGR had no marked effect on the quality of general movements or on the results of the neurological examination at the age of 1 year. PMID- 1587225 TI - Fetal breathing movements are not a good indicator of lung development after premature rupture of membranes and oligohydramnios--a preliminary study. AB - The effect of severe oligohydramnios (due to prolonged premature rupture of the membranes (PROM)) on breathing movements and lung development was studied longitudinally in 11 human fetuses. Prenatally, fetal breathing movements (FBM) were scored off-line from weekly, 1 h during ultrasound recordings (n = 47). In each recording, the incidence of FBM was scored according to 4 different methods. Postnatally, the cases were retrospectively assigned to a group with normal (n = 4), partially hypoplastic (n = 3), or hypoplastic (n = 4) lungs. Compared to control fetuses, the percentage of time spent breathing (%FBM) was low (2-5%) and did not increase with gestational age. Large inter-individual and intra individual variations in the %FBM were found in all 3 diagnostic groups. Evaluation of the %FBM according to the 4 different methods revealed no significant differences between the 3 groups. We conclude that lung development is, at least partly, independent of the incidence of FBM. Furthermore, the analysis of FBM cannot reliably predict lung development in fetuses with oligohydramnios due to PROM. PMID- 1587226 TI - Visual acuity in low birth weight (1500-2500 g) neonates. AB - Binocular grating acuity was tested in 138 low birth weight (LBW) neonates (birth weights ranging from 1500 to 2500 g) by means of the prototype version of the Acuity Card Procedure. No surrounding screen was used. Mean visual acuity of 107 neonates successfully assessed at mean corrected ages of -1.9 weeks (+/- 1.9 weeks) amounted to 0.58 cycles/degree (S.D. 0.71 octaves). Success rate was 77.5%. Mean postnatal age was 2.3 weeks (+/- 1.6 weeks). Acuity values of various subgroups ranged between 0.68 cycles/degree (S.D. 1.3 octaves) in low-risk, small for gestational age (SGA) preterms (n = 7), to 0.56 cycles/degree (S.D. 0.7 octaves) in SGA fullterms (n = 34), independent whether at low-or at high-risk. These differences were not significant, although with multiple regression analysis with adjustment for corrected age of testing, mean acuity of low-risk preterms was slightly better than of low-risk fullterms (P = 0.055). No significant change of acuity over corrected age could be demonstrated, except for a slight progress (r = 0.57; P less than 0.05) in the subgroup of 13 low-risk fullterms. The high variability of acuity values in neonates and the slow acuity development at term age hamper assessment of differences between various subgroups of neonates. PMID- 1587227 TI - Heart rate variability in normal sleeping full-term and preterm neonates. AB - To assess maturation of the Autonomic Nervous System (ANS) and sleep states, Heart Rate Variability (HRV) was studied in 24 healthy sleeping newborns, aged from 31 to 41 weeks, conceptional age (CA). Spectral analysis of the interbeat interval (RR) signal, was performed by Short-Time Fourier Transform, in three frequency bands: high (HF), of purely vagal origin, mid (MF), and low (LF), vagal and sympathetic, thus allowing evaluation of both branches of the ANS, observed in Active Sleep (AS = REM Sleep) and in Quiet Sleep (QS = nREM Sleep). Principal Component Analysis, Discriminant Analysis, and hypothesis tests were used to investigate the evolution of spectral variables and their relation with sleep states. HF, MF, LF, and mean RR all increased with age; the differences from the premature to the full-term group, were more marked, as a whole, in AS than in QS. HF showed the highest increase from the premature (31-36 weeks CA) to the intermediate (37-38) group, whereas LF showed equal differences from the premature to the intermediate, and from the intermediate to the full-term (39-41) groups. These results suggest a steep increase in vagal tone at 37-38 weeks CA, with stability afterwards, and a more regular increase in sympathetic tone from 31 to 41 weeks CA. PMID- 1587228 TI - Intrauterine growth and spastic cerebral palsy II. The association with morphology at birth. AB - This study tests the hypothesis that children with spastic cerebral palsy had different birth morphologies, defined in terms of their weight, length, head circumference, ponderal index and length to head circumference ratio, from that of the normal liveborn population. An earlier study showed a highly significant association of spastic cerebral palsy with low birthweight for gestational age in infants over 34 weeks gestation at delivery. This analysis defines morphological measurements as "abnormal" if not within the 10th-90th percentile ranges of appropriate total liveborn populations. The proportions with combinations of such measurements in 104 cases of spastic cerebral palsy from a population register of cerebral palsy are compared with those in a total liveborn population. Categories of 'abnormal' measurements associated with increased risk contained 44.4% of cases in excess of the proportion observed in the total population. More than half these excess cases were short for their gestation (suggesting size deficits originating before the 3rd trimester) and tended to have more severe forms of cerebral palsy. A further excess of 7.4% of cases had a head circumference above their 90th percentile: these generally developed mild cerebral palsy. PMID- 1587229 TI - [Evaluation of evoked potential or event-related potential mapping]. AB - Strategies for the evaluation of EP and ERP maps are discussed. Spatial interpolation is presented. The reference does not change the landscape but the wave shapes, the baselines change the landscape but not the wave shapes. Electric strength of the map is assessed using Global Field Power, whereby non-ambivalent component latencies can be established. Map landscapes are compared using Global Dissimilarity. Maps are classified using extracted landscape descriptors: locations of minimal and maximal potential, locations of the centroids of the positive and negative map area, reduction to a three-dimensional model dipole source. Adaptive segmentation into echoes of stable landscape (functional microstates) based on landscape descriptors is discussed. Diagnostic and physiological-functional interpretation of the results ought to be distinguished. PMID- 1587230 TI - [Satellite potentials: definition, normal values and validity in the detection of mild myogenic lesions]. AB - From the right m. biceps brachii and the right m. rectus femoris of 28 healthy women aged 19 to 30 years and 16 possible and obligate Duchenne-carriers aged 26 to 40 years we recorded 20 motor unit action potentials each. A satellite potential was defined as electrical activity following or preceding the main component and separated from it by an isoelectrical interval of at least 1, 2 or 3 ms. The most appropriate of these 3 satellite potential definitions is the one that proceeds from a 1 ms minimum interval, because it allows the detection of more satellite potentials than the two others. Applying this definition (minimum interval between the main component and the satellite potential 1 ms) to our controls data we computed a mean interval duration of 5 (m. biceps brachii) respectively 3.4 ms (m. rectus femoris), a mean satellite potential duration of 4.4 (m. biceps brachii) respectively 3.7 ms (m. rectus femoris) and a mean satellite rate of either 3.9 (m. biceps brachii) or 1.6% (m. rectus femoris). We observed up to 3 motor unit action potentials with a satellite potential and up to 1 polyphasic motor unit action potential with a satellite potential per 20 motor unit action potentials. There was little difference between the controls and the Duchenne-carriers satellite parameter means. Only the m. rectus femoris satellite potential duration was increased in Duchenne-carriers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587231 TI - [Normal values and age-related changes in magneto-electric evoked compound muscle potentials]. AB - A number of 57 normal subjects was investigated using transcranial magnetic stimulation of the motor cortex and transcutaneous magnetic stimulation of the spinal nerve root in order to obtain normative data for central and peripheral motor latencies. Under standardized conditions (site of stimulation, stimulus intensity, degree of voluntary tonic background activation) muscle compound action potentials were recorded from different muscles of the upper and lower extremity: M. biceps brachii, M. extensor carpi radialis, M. interosseus dorsalis I, M. vastus medialis, M. tibialis anterior, and M. extensor digitorum brevis. Onset latency, peak to peak amplitude (% of maximal M-wave), duration and configuration of the muscle compound action potentials were evaluated (Fig. 1 and Tab. 1-6). Central and peripheral motor latencies were determined by stimulation over two different points of the neuraxis (cortex/cervical or lumbar nerve roots). Central motor latencies were calculated by subtracting the peripheral conduction time from the onset latency of the fastest cortically evoked muscle response. Not only the peripheral but also the central motor latencies were found to increase in higher ages (Tab. 6). This has to be taken into account when elderly patients are examined for diagnosis of disorders of the descending motor tracts. PMID- 1587232 TI - [Transcranial magnetic stimulation in the cranial nerve region in cranio-cerebral injuries]. AB - By means of transcranial magnetic stimulation bilateral compound muscle action potentials of long latency and ipsilateral potentials of short latency can be obtained in muscles supplied by cranial nerves. In this study motor evoked potentials were recorded from the mentalis muscle of 14 patients with traumatic brain lesions. These results were compared with clinical and radiological as well as other neurophysiological examinations. In spite of the absence of paralysis in muscles supplied by the facial nerve, 9 patients showed pathological long-latency responses, which correlated with the localisation of the paralysis of the limbs. In contrast to this, the degree of pathological latencies of motor evoked potentials did not correspond with the degree of paresis in different patients. A prediction concerning the clinical outcome could not be made by the results of motor evoked potentials. The clinical data showed a poor correlation with the structural brain lesions seen in the CT-scan and the results of EEG, BAEP and orbicularis oculi reflex examination. In conclusion, transcranial magnetic stimulation of cranial nerves proved to be a sensitive method for the evaluation of degree and localization of motor deficits following traumatic brain lesion and seems to be superior to the other examinations compared. PMID- 1587233 TI - [Excitability of the blink reflex during self-elicitation or elicitation by others]. AB - Electrically evoked blink reflexes were studied in 24 healthy subjects in different conditions of elicitation. In one condition the electrical shock was delivered by the experimenter; in a second condition the subject triggered the stimulus himself by manually operating a switch. The different conditions were investigated relaxed or clenching the fist with left hand. Moreover, in 3 subjects the stimulus was given in various delays after the occurrence of the EMG activity of the forearm flexor muscles due to a ballistic wrist flexion. The latencies and peak to peak amplitudes of the ipsi- and contralateral early and late responses were analysed. Voluntary sustained contraction of the left hand (fist) caused no significant modification of the blink reflex. Self-triggering of the stimulus had a facilitating influence on the early components (R1, R1') and an inhibitory effect on the late components (R2, R2'). In EMG triggered self stimulation the R2-inhibition could already be seen at a delay of 0 ms. From a delay of 10 ms on the suppression was still more pronounced and recovered over the following 500-1000 ms. We conclude, that the reflex alterations are not due to the outflow of the motor cortex, but to the conditioning effect of self elicitation. The influence on the excitability of the blink reflex resemble that described in the literature for the conditioning effect of an acoustic or visual stimulus. We suggest involvement of the same interneuron network on the condition of self-eliciting. PMID- 1587234 TI - [Pauses in masseter innervation (silent periods) following stimulation of the median nerve, the cervical plexus and the mental nerve]. AB - In 20 healthy volunteers, a bilateral masseter silent period (Mass SP) was constantly evoked by stimulating the mental nerve (latency: x = 13.95 +/- 4.3 ms) and cervical plexus (latency: x = 20.2 +/- 3.7 ms). This was also the case with median nerve stimulation (latency: x = 54.4 +/- 13.1 ms) in 19 of the 20 subjects. Utilizing magnetic stimulation of the lumbal roots, the Mass SP was elicited in 3 of 10 subjects and showed marked habituation. No Mass SP was observed with stimulation of the long nerves of the lower limbs. The central loop of the reflex represents a stable connection between the spinal cord cervical region and the trigeminal motor nuclei. The Mass SP may be abolished in circumscribed brainstem lesions and thus may serve for localizing lower brainstem involvement. PMID- 1587235 TI - Endoscopic mucosectomy for early gastric cancer using modified strip biopsy. AB - We present a modification of strip biopsy (SB), one of the endoscopic treatment modalities for early gastric cancer. Using a side-viewing endoscope and a special electrocautery snare, we treated 6 patients with early carcinoma of the intestinal type with this modified strip biopsy (MSB). All tumors could be completely resected and 5 patients were not operated on: All 5 remained tumor free at follow-up of at least one year. These results compared favorably with a historical control group of 17 patients with early gastric cancer treated with conventional strip biopsy. We therefore recommend applying our new method of MSB especially in the intestinal type of early gastric carcinoma; these preliminary data however, need confirmation in larger trials. PMID- 1587236 TI - Endoscopic treatment of submucosal lesions of the gastrointestinal tract. AB - Fourteen of symptomatic submucosal lesions located in the esophagus (n = 4), stomach (n = 4), duodenum (n = 1) and colon (n = 5) were treated by means of endoscopy. Treatment selection criteria for tumours (n = 10) were presence of a pedunculated tumour, or presence of a sessile tumour with a base smaller than 2 cm which originated in the upper wall layers, as judged by the mobility of the lesion. All tumours but one were successfully and completely removed by snare cauterization. The failure was a gastric fibroma which was incompletely resected; bleeding ensued rendering emergency surgery necessary. Mucosal cysts in the esophagus and colon were treated by either snare polypectomy in the case of smaller lesions or drainage in the case of larger cysts. Follow-up for 5 to 12 months (mean 8.7 months) in the 13 cases treated by means of endoscopy alone did not reveal recurrence. These preliminary results show that endoscopic treatment of smaller and superficially originating submucosal tumours may be a feasible alternative to surgery, however meticulous patient selection is necessary to avoid major complications. PMID- 1587237 TI - Evaluation of endoscopic sphincterotomy in sphincter of Oddi dysfunction. AB - In this prospective study the efficacy of endoscopic sphincterotomy was evaluated in ten post-cholecystectomy patients with clinical and biliary manometric evidence of SO dysfunction. Ten patients (8 females, 2 males, median age 59 years) were assessed at a median period of 24 months (range 12-48) after endoscopic sphincterotomy. Eight of the ten patients (80%) were symptomatically improved after endoscopic sphincterotomy although only four were totally asymptomatic. The two patients who had unchanged symptoms after sphincterotomy have since had alternative diagnoses made and have improved on appropriate therapy. It is concluded that endoscopic sphincterotomy is effective in relieving symptoms in post-cholecystectomy patients with clinical and manometric evidence of SO dysfunction. PMID- 1587238 TI - A modified technique for endoscopic mucosal resection of small early gastric carcinomas. AB - Endoscopic gastric mucosal resection (EGMR) is increasingly employed in early gastric cancer to remove the tumour with the surrounding mucosa and part of the submucosa after submucosal saline injection and staining to define the extent of the lesion. This study presents preliminary experience with a modified EGMR technique in five patients which allows more precise targeting and resection of the lesions. The time required for this procedure was less than 30 minutes in each case. All lesions were completely removed. In two patients, however, tumour growth invaded the submucosa and these patients therefore underwent subsequent surgery. Three patients with carcinoma confined to the mucosa were tumour-free at follow-up with repeat endoscopy and biopsy after 7 to 23 months. PMID- 1587239 TI - Fistuloscopy for the management of postoperative intra-abdominal abscesses. AB - A new technique of fistuloscopy for evaluation and treatment of postoperative intra-abdominal abscesses is described which was used in 8 patients in whom drainage of abscesses following surgery was insufficient. A cholangiofiberscope was introduced into the fistula canal produced by the postoperative drainage. Fistuloscopy was combined with fistulography in all cases to delineate the extent of the inflammatory process. The guidewire was then placed under visual control through the endoscope followed by re-introduction of the drainage tube until a position most effective for pus drainage was achieved. Following this procedure, fever resolved in all 8 patients. Fistuloscopy is recommended to achieve sufficient drainage of intra-abdominal abscesses in those cases where percutaneous ultrasound- or CT-guided drainage fails to lead to significant clinical improvement. PMID- 1587240 TI - Clinical use of new video-endoscopes (EVIS 100 and 200). AB - The authors report on their clinical experience with two new videoendoscopes developed in cooperation with Olympus Co. One of them is an instantaneous image method videoendoscope (EVIS 100), the other produces sequential images (EVIS 200). EVIS 100 is as compact as a fiberscope; EVIS 200 has the special advantages of electronic magnification, the use of infrared rays and image display of hemoglobin concentration in the tissue. In clinical application in 245 patients examined with EVIS 100 and 30 cases with EVIS 200, both instruments were found to be satisfactory in terms of daily use; EVIS 200 could be applied in further endoscopic research. In our opinion videoendoscopes will replace conventional fiberscopes in the future. PMID- 1587241 TI - Optical resolution and color performance of electronic endoscopes. AB - We studied the optical and color performance of Olympus fiber- and electronic endoscopes, including the EVIS 100 and EVIS 200 series. The measurements showed that the optical resolution of new generation videoendoscopes equals or exceeds that of fiberendoscopes. The close-up focusing ability has been extended. The color performance of the new EVIS 200 gastroscope enables clear distinction of all mucosal hues. PMID- 1587242 TI - Endoscopic treatment of gastro-intestinal tumours: can surgery be avoided? PMID- 1587243 TI - Use of strip biopsy in a case of early duodenal cancer. AB - In a 67-year-old man referred for investigation of an abdominal mass, upper gastrointestinal endoscopy incidentally revealed a polypoid lesion with a central depression in the duodenum. The abdominal mass causing gastric compression was shown by ultrasonography and CT scan to be cyst anterior to the pancreas. Biopsy of the duodenal lesion, however, was suggestive of carcinoma. Strip biopsy was therefore performed. Histological examination showed a tubular adenocarcinoma with invasion limited to the mucosa, and indicated that complete endoscopic resection had been achieved. Follow-up over ten months did not reveal recurrence of the tumor. Strip biopsy would appear to be a safe and efficient method for management of early gastrointestinal tract cancer also in the duodenum. PMID- 1587244 TI - Feeding tube perforation as a complication of percutaneous endoscopic gastrostomy. PMID- 1587245 TI - Changing of defect PEG-tubes. PMID- 1587246 TI - Mallory-Weiss tear after pneumatic dilatation in achalasia. PMID- 1587247 TI - Irreversible trapping of DNA during crossed-field gel electrophoresis. AB - Using an original protocol with a rotating gel electrophoresis apparatus, it is shown that duplex DNA undergoing crossed-field electrophoresis in agarose gets trapped in the gel when the field is increased above a threshold value which decreases with the chain length and depends on the angle between the fields in a non-monotonous manner. This trapping is irreversible, i.e. once trapped at a high field strength, chains are unable to resume their motion when the field is returned to a lower value at which they moved prior to trapping. A model of trapping by "tight knots" is proposed. It predicts a trapping threshold proportional to the inverse square of the electric field, in qualitative agreement with the data. The implications of our results for the separation of large DNA molecules are discussed. PMID- 1587248 TI - A genetic factor model for the statistical analysis of multilocus DNA fingerprints. AB - A novel concept is described for the statistical analysis of multilocus DNA fingerprints. Utilizing this method, it is shown by simulation that the application of multilocus DNA fingerprints to paternity testing is robust against deviations from idealistic assumptions made about underlying models and parameters. Partial homozygosity, allelism and linkage at the DNA loci involved, as well as variations in estimates of band-sharing probabilities were studied for effects on the resulting paternity probabilities. None of the above-mentioned phenomena appear to change these values to an extent relevant for decision making in paternity cases. PMID- 1587249 TI - Localization of separated protein bands in unstained electrophoresed polyacrylamide gradient slab gel. AB - Polyacrylamide gel electrophoresis has become the most widely used separation method in biological science. Once electrophoresis is complete the protein bands must be localized prior to excision. A zig-zag gel cutter is described which cuts a strip of gel from the side of a slab gradient gel or a gel of uniform concentration in peaks and valleys. The location of the protein of interest is determined by counting the number of peaks on the stained side strip. The portion of the unstained gel corresponding to the same count (number of valleys) is cut to recover the protein of interest from the main gel for further manipulations. PMID- 1587250 TI - Capillary electrophoresis in agarose solutions: extension of size separations to DNA of 12 kb in length. AB - The upper limit of the size range of DNA amenable to separation in agarose solutions above their gelling temperature, using capillary zone electrophoresis apparatus, was increased to 12 kb. The plot of log(bp) vs. mobility derived from electrophoresis in 1.7% agarose solution is biphasic, exhibiting higher resolving power for DNA less than 1 kb in size than that of larger sizes. Resolving power for DNA larger than 1 kb increased when the agarose concentration was increased in the range of 1.0-2.6%. It was similar in solutions at 40 degrees C of SeaPrep and SeaPlaque agaroses as well as in Acrylaide (trade names are those of the manufacturer). However, the resolving power of SeaPrep agarose at 25 degrees C was inferior to that at 40 degrees C. Concave plots of log(mobility) vs. concentration of the agarose solutions are those predicted under the assumption that the effective "equivalent radius" of the DNA molecule diminishes with increasing agarose concentration in the investigated concentration range up to 2.6%. PMID- 1587251 TI - Capillary electrophoretic analysis of flavonoids. AB - Combining the effects of electrophoresis and electroendosmosis, flavonoids were separated in less than ten minutes in a fused silica capillary tube with a borate buffer adjusted to pH 10. An increase in the concentration of borate from 0.1 to 0.2 M resulted in longer migration times due to a decrease in electroosmotic flow, but also in improved selectivity and higher resolution of flavonoids. The calibration curve of rutin showed a detection limit of 0.02 mg/mL and linearity over its pharmaceutical concentration range. Using an internal standard of known concentration, the content of rutin in a methanolic extract of Sambuci flos could be determined with a coefficient of variation as small as 3.8% by the molar ratio peak area ratio method. PMID- 1587252 TI - Use of cyclodextrins for the enantioselective separation of ergot alkaloids by capillary zone electrophoresis. AB - Ergot alkaloid enantiomer derivatives were resolved using capillary zone electrophoresis. The effect of cyclodextrins, added to the background electrolyte, on the migration time and the resolution was studied. Good separation for epimeric ergot alkaloid derivatives was also obtained using phosphate buffer at pH 2.5. Separation was improved by supplementing the background electrolyte with 30 mM of gamma-cyclodextrin. Good resolution of racemic ergot alkaloid derivatives in their enantiomers was achieved in a background electrolyte containing either beta-cyclodextrin or its derivative, or gamma-cyclodextrin. PMID- 1587253 TI - High speed electrophoresis simulation for optimization of continuous flow electrophoresis and high performance capillary techniques: Part I. Computer model. AB - A computer program for high-speed simulation and optimization of electrophoretic processes has been developed for carrier-free systems of all kinds. The calculations are based on the one-dimensional dynamic (transient-state) model. The three-dimensional geometry of the simulation space can be chosen deliberately. With a highly efficient transport algorithm instead of complicated integration schemes for the transport equations, the calculation time can be effectively spent on various important parameters such as ionic strength, temperature, Joule heat, activity coefficients and concentration changes due to membranes. The parameter set of any carrier free electrophoretic method (i.e., continuous-flow electrophoresis, capillary isotachophoresis and high performance capillary zone electrophoresis) can be imported directly into the computer program by means of a graphic user interface. The program performs overnight simulation of any electrophoretic system containing up to 15 components. PMID- 1587254 TI - Traveling-wave dielectrophoresis of microparticles. AB - The traveling-wave-induced linear transfer of dielectric particles like living cells and artificial objects of microscopic dimensions is analyzed. It is shown that the electrode geometries must correspond to particle sizes to allow an effective manipulation of particles immersed in weakly electrolytic solutions by high frequency traveling waves. The theoretical model elaborated in this paper is in good agreement with experimental results obtained in microfabricated chambers of linearly arranged electrodes. It explains the behavior of homogeneous cellulose spheres as well as that of membrane-covered pine polls. The traveling wave-driven electrodes are described by a superposition of time-dependent point charges. Subsequently, each of these point charges has to be considered as polarizing the dielectric particle and interacting with the polarized particle. This results in forces which effectively translocate the particle. PMID- 1587255 TI - Ti/IrO2 as anode and Zr as cathode in multicompartment electrolyzers with Immobiline membranes. AB - Multicompartment electrolyzers with isoelectric Immobiline membranes are used for large-scale preparative protein purification. A series of isoelectric membranes, of defined pI values, is utilized for keeping any desired species isoelectric within each compartment of the electrolyzer. It is preferable to have electrode disks of the same surface area as the membranes for a proper performance of the instrument because electrolyte solutions of low conductivity are used. The use of Pt disks would be quite expensive; we therefore propose using Zr as a cathode and Ti/IrO2 as an anode in the electrodic compartments. This pairing of electrodes seems to give the same performance as Pt wires. Also, conventional isoelectric focusing, as well as isoelectric focusing in immobilized pH gradients, both requiring a good contact area between gel and electrodes, would benefit by using flat laminae of these metals as electrodes. PMID- 1587256 TI - High yield electroblotting onto polyvinylidene difluoride membranes from polyacrylamide gels. AB - Optimal conditions of electroblotting that led to high protein recovery on polyvinylidene difluoride (PVDF) membranes were determined for sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). SDS concentrations in the gel and transfer buffer were found to be the most important factors affecting the amount of protein recovered on the PVDF membrane. The largest loss occurred during the first 10-30 min of transfer due to the relatively high initial SDS concentration in the gel. During this initial stage of transfer, most of the protein passed through the primary membrane and was partially retained on secondary and tertiary membranes. The value of presoaking gels prior to transfer to reduce the amount of SDS was evaluated by quantitating free SDS densitometrically and by correlating the reduced SDS concentration with increased electroblotting efficiency from presoaked gels. Transfer time was evaluated and no "overtransfer" was found even after very long transfer times. These results clearly indicate that proteins electroblotted onto PVDF membranes were tightly bound and could not be released by extending the transfer time. The effects of methanol and SDS concentrations on protein adsorption from solution to PVDF were also determined quantitatively. The results of this study strongly suggest that proteins fully saturated with SDS cannot bind efficiently to PVDF membranes. Since SDS is necessary for high protein mobility, the challenge in efficient electroblotting is to maintain an optimal SDS concentration which is high enough to permit effective removal from the gel and low enough to permit effective binding to the PVDF membrane. For 1.5 mm thick gels containing 0.2% SDS, presoaking the gel for 15-20 min in transfer buffer with 10% methanol prior to electroblotting provided the best recovery on the primary membrane. PMID- 1587257 TI - Separation of peptides on Empore thin-layer chromatography sheets and blotting onto polyvinylidene difluoride membranes with subsequent gas phase sequencing. AB - Methods for the separation of peptides on a new type of thin-layer chromatography (TLC) sheet and blotting onto polyvinylidene difluoride (PVDF) membranes with subsequent gas phase sequencing are described. For validation, the A and B chain of insulin were chromatographed on Empore TLC sheets and either extracted or blotted onto PVDF membranes. The advantages and disadvantages of thin-layer chromatography on Empore sheets versus high performance liquid chromatography (HPLC) are discussed, along with the possibility of combining the two methods. In addition, TLC was combined with electrophoresis (fingerprinting) for the separation of complex peptide mixtures. Blotting from TLC sheets onto PVDF membranes was performed in two ways: contact diffusion and electrophoretic transfer. In our experiments electroblotting was more effective. Amino acid sequence determination of the B chain of insulin was possible both after extraction from the TLC sheet and after blotting onto PVDF membranes. In the former case, liquid phase sequencing and, in the latter case, gas phase sequencing was performed. The possibility to blot from TLC sheets onto membranes, e.g. PVDF, may prove useful in many fields, for example in biochemistry, and in molecular and cell biology. PMID- 1587258 TI - A gel retardation assay system for studying protein binding to simple repetitive DNA sequences. AB - Simple repetitive DNA sequences have been regarded as mere "junk" present in all eukaryotic genomes. In fact, mixed simple repeat (gt)n(ga)m sequences are present in major histocompatibility complex MHC-DRB genes for long evolutionary times, including such distant animals as artiodactyla and man. We describe herein an unsophisticated method which reveals that at least certain simple repetitive (gt)n(ga)m sequences bind nuclear proteins and show characteristics of a specific DNA-protein interaction via gel retardation. PMID- 1587259 TI - Reduced chemical and radioactive liquid waste during electrophoresis using polymerized electrode gels. AB - Using polyacrylamide electrode gels during horizontal sodium lauryl sulfate polyacrylamide electrophoresis of radiolabeled proteins instead of electrode papers reaching into electrode buffer reservoirs, silver staining is improved and we reduce chemical and radioactive liquid waste during electrophoresis. PMID- 1587260 TI - Equipment for rapid homogenization of high numbers of plant tissue for electrophoretic analysis of proteins. AB - A homogenizing system was developed to process multiple samples of various plant tissues. The equipment consists of a motor-driven stainless steel homogenizer that fits perfectly into a hole of a disposable plate. Hard plant material like melon or squash seeds (maximal length of 1.4 cm) could be homogenized within 10 s by forcing the homogenizer towards the bottom of a 24- or 48-well tissue culture plate. Smaller seeds could be homogenized within 10 s in a similar way using a 96 well tissue culture plate. Leaf tissue, or other types of soft plant tissue, could be homogenized with the same equipment. For homogenization of small samples, e.g. pistils of small flowers, a 60-well Terasaki plate was used. For homogenization of several hundreds of leaf tissue samples, an apparatus was developed that contains 12 homogenizers driven simultaneously by an electromotor. A tissue culture plate containing 96 leaf samples could be handled in this way in less than 10 min. The performance of the equipment was evaluated by analyzing homogenates of several types of plant tissue by different electrophoretic techniques. PMID- 1587261 TI - The use of radioactive bacteriophage proteins as X-Y markers for silver stained two-dimensional electrophoresis gels and quantification of the patterns. AB - We have demonstrated the feasibility of using bacteriophage ghost proteins, tritiated by metabolic labeling, as a set of standard markers for two-dimensional gels in which the proteins are to be detected by silver staining. The results indicate that a 2.5 microgram load of phage proteins yields a reproducible silver pattern of 48 spots. The spots can also be readily identified by radioautography and radiofluorography, establishing their value as a standard constellation of markers. Quantification of these patterns by computerized densitometry indicates a general agreement between detection by silver staining and detection by radiofluorography. PMID- 1587262 TI - Two-dimensional electrophoresis of the total polypeptides in ripe red grape berries. AB - The total polypeptide composition of mature grape berries was analyzed by one dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and two dimensional electrophoresis (isoelectric focusing in the first dimension followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in the second dimension), followed by Coomassie Blue and nitrate silver staining, respectively. Adapted methods for total protein preparation of grapes and for two-dimensional gel electrophoretic separation of polypeptides are presented. The grape patterns presented up to 52 fractions with Mrs ranging from 15,000 to 110,000. The polypeptides displayed pIs from 4.6 to 7.3. A group of spots from Mr 28,000 to 83,000 and with a pI from 4.6 to 5.4 was strongly silver stained. The Mr 28,000 spot, pI 4.6, was revealed to be a complex of four fractions. Reproducible separations were obtained with the different carrier ampholyte mixtures tested. PMID- 1587263 TI - A rapid periodic acid-Schiff staining procedure for the detection of glycoproteins using the PhastSystem. AB - A procedure for the analysis of glycoproteins and glycopeptides using the PhastSystem with detection by the periodic acid-Schiff stain is described. Following sodium dodecyl sulfate or nondenaturing polyacrylamide gel electrophoresis and also isoelectric focusing, samples are stained directly for the presence of carbohydrates. By using the PhastSystem, the method is rapid, sensitive, reliable and allows storage of the gels without a change in the stain. As little as 0.1 micrograms of protein-associated carbohydrates can be detected. The staining procedure is also used following isoelectric focusing of mucin derived glycopeptides to visualize their charge differences and the increase of their isoelectric point after neuraminidase treatment. PMID- 1587264 TI - Substrate preferences of glutamic-acid-specific endopeptidases assessed by synthetic peptide substrates based on intramolecular fluorescence quenching. AB - The substrate preferences of the easily available Glu/Asp-specific enzymes from Staphyllococcus aureus (V8), Bacillus licheniformis and Streptomyces griseus have been extensively investigated using a series of synthetic peptide substrates, containing an N-terminal anthraniloyl group and a 3-nitrotyrosine close to the C terminus, allowing the fluorimetric monitoring of substrate hydrolysis by the decrease in intramolecular quenching. All three enzymes hydrolysed Glu-Xaa peptide bonds approximately 1000-fold faster than Asp-Xaa bonds and they are consequently more appropriately termed Glu-specific enzymes. The difference in kcat/Km for the hydrolysis of substrates with Glu and Asp is primarily due to a difference in kcat. The enzymes appear to hydrolyse all types of Glu-Xaa bonds, although those with Xaa as Asp and, in particular, Xaa as Pro, are hydrolysed with very low rates. The influence of the nature of the amino acid residues at the substrate positions P2, P3, P4, P'1 and P'2 has been determined and it is shown that the enzyme from S. griseus exhibits the most narrow substrate preference. The results are useful in connection with fragmentation of proteins for sequencing purposes as well as for cleavage of fusion proteins. PMID- 1587265 TI - Regulation of cyclooxygenase and thromboxane synthase in human monocytes. AB - Stimulation of human monocytes by lipopolysaccharide or phorbol ester resulted in an increase in thromboxane-B2 and prostaglandin-E2 production, whereas interleukin 1, tumour necrosis factor alpha and leukotriene C4 exerted no effects. Inhibitors of protein kinase C suppressed these increases. The activity of cyclooxygenase was induced 3.2-fold by an 8-h stimulation, whereas thromboxane synthase and prostaglandin-E-isomerase activities remained unchanged. A glucocorticoid, dexamethasone, blocked both basal and induced prostanoid release, as well as cyclooxygenase activity. By immunoprecipitation, we were able to demonstrate an enhanced de novo synthesis of cyclooxygenase protein induced by lipopolysaccharide and phorbol ester. Dexamethasone suppressed cyclooxygenase synthesis, whereas thromboxane synthase was induced. For cyclooxygenase, we calculated a half-life of 3.2 h in human monocytes, and for thromboxane synthase, a half-life of 28 h. These results suggest that the regulation of differential prostanoid production mainly occurs by up and down regulation of cyclooxygenase. PMID- 1587266 TI - Multiphasic denaturation of the lambda repressor by urea and its implications for the repressor structure. AB - Urea denaturation of the lambda repressor has been studied by fluorescence and circular dichroic spectroscopies. Three phases of denaturation could be detected which we have assigned to part of the C-terminal domain, N-terminal domain and subunit dissociation coupled with further denaturation of the rest of the C terminal domain at increasing urea concentrations. Acrylamide quenching suggests that at least one of the three tryptophan residues of the lambda repressor is in a different environment and its emission maximum is considerably blue-shifted. The transition in low urea concentration (midpoint approximately 2 M) affects the environment of this tryptophan residue, which is located in the C-terminal domain. Removal of the hinge and the N-terminal domain shifts this transition towards even lower urea concentrations, indicating the presence of interaction between hinge on N-terminal and C-terminal domains in the intact repressor. PMID- 1587267 TI - The glutamate dehydrogenase gene of Clostridium symbiosum. Cloning by polymerase chain reaction, sequence analysis and over-expression in Escherichia coli. AB - The gene encoding the NAD(+)-dependent glutamate dehydrogenase (GDH) of Clostridium symbiosum was cloned using the polymerase chain reaction (PCR) because it could not be recovered by standard techniques. The nucleotide sequence of the gdh gene was determined and it was overexpressed from the controllable tac promoter in Escherichia coli so that active clostridial GDH represented 20% of total cell protein. The recombinant plasmid complemented the nutritional lesion of an E. coli glutamate auxotroph. There was a marked difference between the nucleotide compositions of the coding region (G + C = 52%) and the flanking sequences (G + C = 30% and 37%). The structural gene encoded a polypeptide of 450 amino acid residues and relative molecular mass (M(r) 49,295 which corresponds to a single subunit of the hexameric enzyme. The DNA-derived amino acid sequence was consistent with a partial sequence from tryptic and cyanogen bromide peptides of the clostridial enzyme. The N-terminal amino acid sequence matched that of the purified protein, indicating that the initiating methionine is removed post translationally, as in the natural host. The amino acid sequence is similar to those of other bacterial GDHs although it has a Gly-Xaa-Gly-Xaa-Xaa-Ala motif in the NAD(+)-binding domain, which is more typical of the NADP(+)-dependent enzymes. The sequence data now permit a detailed interpretation of the X-ray crystallographic structure of the enzyme and the cloning and expression of the clostridial gene will facilitate site-directed mutagenesis. PMID- 1587268 TI - The interaction of thrombin with fibrinogen. A structural basis for its specificity. AB - The structure of the ternary complex of human alpha-thrombin with a covalently bound analogue of fibrinopeptide A and a C-terminal hirudin peptide has been determined by X-ray diffraction methods at 0.25 nm resolution. Fibrinopeptide A folds in a compact manner, bringing together hydrophobic residues that slot into the apolar binding site of human alpha-thrombin. Fibrinogen residue Phe8 occupies the aryl-binding site of thrombin, adjacent to fibrinogen residues Leu9 and Val15 in the S2 subsite. The species diversity of fibrinopeptide A is analysed with respect to its conformation and its interaction with thrombin. The non-covalently attached peptide fragment hirudin(54-65) exhibits an identical conformation to that observed in the hirudin-thrombin complex. The occupancy of the secondary fibrinogen-recognition exosite by this peptide imposes restrictions on the manner of fibrinogen binding. The surface topology of the thrombin molecule indicates positions P1'-P3', differ from those of the canonical serine-proteinase inhibitors, suggesting a mechanical model for the switching of thrombin activity from fibrinogen cleavage to protein-C activation on thrombomodulin complex formation. The multiple interactions between thrombin and fibrinogen provide an explanation for the narrow specificity of thrombin. Structural grounds can be put forward for certain congenital clotting disorders. PMID- 1587269 TI - alpha-D-galactose-bearing glycoproteins on the surface of stimulated murine peritoneal macrophages. Biochemical and immunochemical characterization of purified glycoproteins. AB - Two glycoproteins were isolated from lysates of thioglycollate-stimulated, murine peritoneal macrophages by affinity chromatography on immobilized Griffonia simplicifolia I lectin and by preparative SDS/PAGE. The glycoproteins were readily labeled on the surface of intact macrophages with 3H and 125I. The labeled glycoproteins migrated as broad bands of molecular mass 92-109 kDa and 115-125 kDa. The mobility of the glycoproteins decreased only slightly after reduction with dithiothreitol, indicating the absence of intersubunit disulfide bridges. The 92-kDa and 115-kDa glycoproteins had pI 5.2-5.4 and pI less than or equal to 4, respectively. Digestion of both glycoproteins with alpha galactosidase released 23% of their 3H content and abolished their ability to bind to the G. simplicifolia I lectin, showing that they contain terminal alpha-D galactosyl groups. After reduction with 2-mercaptoethanol, each glycoprotein fraction was sensitive to N-glycanase; the 115-kDa glycoproteins produced a smear with the front at approximately 67 kDa, whereas the 92-kDa glycoprotein gave two bands of 61 kDa and 75 kDa. Unreduced glycoproteins were insensitive to N glycanase, suggesting the presence of intramolecular disulfide bonds. Although each glycoprotein fraction was sensitive to endoglycosidase H, this enzyme produced only slight changes in molecular mass when compared with N-glycanase. From these results as well as from the specificity of the enzymes involved, it is concluded that each glycoprotein fraction contains complex-type oligosaccharides and a small amount of high-mannose and/or hybrid-type oligosaccharides. While each glycoprotein fraction was bound to Datura stramonium lectin, they failed to react with anti-[i-(Den)] serum and their digestion with endo-beta-galactosidase did not cause a band shift in SDS/PAGE. Taken together, these results suggest the presence of N-acetyllactosamine units which are not arrayed in linear form but occur as single units, bound either to C2 and C6, or to C2 and C4, or both, of outer mannosyl residues on complex-type oligosaccharides. The glycoprotein(s) fraction precipitated with anti-[I (Step)] serum, suggesting the presence of branched lactosaminoglycans. Digestion of both glycoprotein fractions with a mixture of sialidase and O-glycanase did not alter their mobility in SDS/PAGE, suggesting a lack or low content of O-linked trisaccharides and tetrasaccharides. Each glycoprotein fraction was bound specifically to Sambucus nigra and Maackia amurensis immobilized lectins, indicating the presence of sialic acid linked alpha 2,6 to subterminal D-galactose or N-acetylgalactosamine residues, and alpha 2,3 to N-acetyllactosamine residues, respectively. PMID- 1587270 TI - Identification of the photosystem I antenna polypeptides in barley. Isolation of three pigment-binding antenna complexes. AB - The light-harvesting antenna of barley photosystem I (LHCI) was isolated from native photosystem I (PSI) complexes and fractionated into three pigment-protein subcomplexes using two consecutive rounds of green gel electrophoresis. Each complex showed a characteristic polypeptide composition and low-temperature fluorescence emission spectrum; they were designated as LHCI-730, LHCI-680A and LHCI-680B. Their four apoproteins of 21, 22, 23 and 25 kDa were purified and NH2 terminal sequences were determined; in the case of the NH2-terminally blocked 25 kDa protein, an internal sequence was obtained after cleavage with endoproteinase Lys-C. This made possible an assignment of the four proteins to the four types (I IV) of genes coding for chlorophyll a/b proteins of PSI (cab or lha genes). The LHCI-730 complex was isolated as a heterodimer composed of the 21-kDa (LHCI type IV) and the 22-kDa (LHCI type I) polypeptides. Each LHCI-680 complex had a single apoprotein. LHCI-680A consisted of the 25-kDa (LHCI type III) and LHCI-680B of the 23-kDa (LHCI type II) polypeptides. LHCI-680B was associated with the non pigmented PSI-E subunit, indicating that this protein may function in the binding of this antenna to the reaction centre. PMID- 1587271 TI - Cloning of the human and mouse type X collagen genes and mapping of the mouse type X collagen gene to chromosome 10. AB - Type X collagen, a homotrimer of alpha 1 (X) polypeptide chains, is specifically expressed by hypertrophic chondrocytes in regions of cartilage undergoing endochondral ossification. We have previously described the isolation of a small fragment of the human type X collagen gene (COL10A1) and its localization to the q21-q22 region of human chromosome 6 [Apte, S., Mattei, M.-G. & Olsen, B. R. (1991) FEBS Lett. 282, 393-396]. Using this fragment as a probe to screen genomic libraries, we report here the isolation of human and mouse genomic clones which contain the major part of the human and mouse type X collagen genes. In both species, the 14-kb genomic clones which were isolated contain a long open reading frame (greater than 2000 bp in length) which codes for the entire C-terminal non collagenous (NC1) domain, the entire collagenous (COL) domain and part of the N terminal non-collagenous (NC2) domain of the alpha 1(X) collagen chain. The human genomic clone contains the major part of the COL10A1 gene, in addition to the region we have previously cloned, and is highly similar to the corresponding portions of the mouse genomic clone (84.5% similarity at the nucleotide level, and 86.1% at the level of the conceptual translation product). The identification of the mouse genomic clone as the alpha 1(X) collagen gene (Col10a1) was confirmed by in situ hybridization of a fragment of the mouse genomic clone to sections from newborn mice. Hybridization was restricted to the hypertrophic chondrocytes of developing chondroepiphyses, being absent in small chondrocytes and in other tissues. Using interspecific backcross analysis, the locus for the mouse alpha 1 (X) collagen gene was assigned to chromosome 10. The cloning and chromosomal mapping of the human and mouse alpha 1 (X) collagen genes now permit the investigation of the possible role of type X collagen gene defects in the genesis of chondrodysplasias in both species and provide data essential for the generation of transgenic mice deficient in type X collagen. PMID- 1587272 TI - Purification and characterization of human salivary-gland prokallikrein from recombinant baculovirus-infected insect cells. AB - A full-length cDNA encoding human salivary-gland preprokallikrein was inserted into the baculovirus Autographa californica nuclear polyhedrosis virus downstream of the polyhedrin promoter. The gene was expressed in transfected Spodoptera frugiperda cells and the recombinant product secreted into the culture medium. By alternating anion-exchange chromatography and gel-filtration steps, twice repeated, prokallikrein was purified to homogeneity, which was confirmed by amino acid analysis and N-terminal sequence determination. The prepropeptide was processed correctly, including the removal of the signal peptide. The resulting proenzyme was found to be glycosylated, had a molecular mass of 35 kDa and an isoelectric point of 4.6. The yield of purified recombinant protein reached a level of 5 mg/l insect cell culture. After trypsin digestion of prokallikrein, the biological activity of the released kallikrein was demonstrated by its specific amidase, esterase and kininogenase activity. The expression and purification of prokallikrein, as described here, offers the opportunity to study the proenzyme activation through protein engineering techniques in detail. PMID- 1587273 TI - Conformational analysis of the melanin-concentrating hormone core by circular dichroic spectroscopy. Disulphide bridge and tyrosine contributions. AB - A detailed circular dichroic (CD) study of the conformational flexibility of the melanin-concentrating hormone core [MCH(5-14)] is reported. Variable pH (2-10) and temperature (-80 degrees to +80 degrees C) in aqueous media reveal that CD contributions from tyrosine, disulphide bridge and the amide backbone can be discriminated. Only below -10 degrees C does a preferred -S-S-conformation (P chirality, dihedral angle phi = 90 +/- 10 degrees) dominate. The amide backbone CD contribution varies over all temperatures (-80 degrees to +80 degrees C) providing evidence for a type-II beta-turn at low temperatures, with the emergence of a type-I beta-turn at higher temperatures. Tyrosine exhibits a special behaviour at pH 7. These conclusions are in broad agreement with published NMR studies. Nevertheless, the MCH(5-14) core is seen to be conformationally flexible in aqueous solution at ambient temperatures. Conformation differences are observed in a non-aqueous environment. PMID- 1587274 TI - Red-edge excitation fluorescence measurements of several two-tryptophan containing proteins. AB - The dependence of the fluorescence emission maximum of the tryptophan residues in several two-tryptophan-containing proteins (horse liver alcohol dehydrogenase, yeast 3-phosphoglycerate kinase, Staphylococcus aureus metalloprotease and bee venom phospholipase A2) on the excitation wavelengths has been studied. Using fluorescence-resolved spectroscopy, we have dissected the contributions of particular tryptophan residues located in different parts of the protein molecule. The results demonstrate that dipolar structural relaxation can occur in the environment of tryptophan residues buried within protein molecules. The observed spectral shifts upon red-edge excitation of these residues can depend on temperature or ligand binding, as demonstrated in case of metalloprotease and alcohol dehydrogenase. No spectral shifts upon red-edge excitation have been observed for tryptophan residues totally exposed to the rapidly relaxing aqueous solvent. PMID- 1587275 TI - Primary structure of hemocyanin subunit c from Panulirus interruptus. AB - The amino acid sequence of the hemocyanin subunit c from the spiny lobster, Panulirus interruptus, has been determined. The elucidation was mainly based on three digests, with CNBr, trypsin and endoproteinase Glu-C, respectively. Additional evidence was obtained by sequencing of peptides from an endoproteinase Lys-C digest. Subunit c is a polypeptide with 661 amino acid residues and with a carbohydrate group attached to residue 476 in the third domain. No heterogeneity was observed. The degree of identity with subunit a is 59%. Some differences with subunit a are an N-terminal extension of six residues, a one-residue C-terminal extension, and a three-residue deletion. Furthermore, carbohydrate attachment is in a different position, as are most half-cystine residues. Limited trypsinolysis resulted in cleavage at the same site as in subunits a and b. PMID- 1587276 TI - Interaction in vitro of scallop muscle arginine kinase with filamentous actin. AB - Scallop muscle arginine kinase binds to F-actin from mollusc and rabbit muscle in vitro. One site of interaction appears to be located in residues 305-325 of a C terminal fragment (residues 285-375) of actin. The binding is hindered in the presence of arginine, Mg(2+)-ADP and NO3-, which form a dead-end complex with the enzyme. F-actin inhibits the enzyme activity non-competitively with respect to Mg(2+)-ATP. As a function of arginine concentration, the inhibition is of the mixed type, where Km is affected more than Vmax. PMID- 1587277 TI - Specific protein kinase from Saccharomyces cerevisiae cells phosphorylating 60S ribosomal proteins. AB - A protein kinase, specific for 60S ribosomal proteins, has been isolated from Saccharomyces cerevisiae cells, purified to almost homogeneity and characterized. The isolated enzyme is not related to other known protein kinases. Enzyme purification comprised three chromatography steps; DEAE-cellulose, phosphocellulose and heparin-Sepharose. SDS/PAGE analysis of the purified enzyme, indicated a molecular mass of around 71 kDa for the stained single protein band. The specific activity of the protein kinase was directed towards the 60S ribosomal proteins L44, L44', L45 and a 38 kDa protein. All the proteins are phosphorylated only at the serine residues. None of the 40S ribosomal proteins were phosphorylated in the presence of the kinase. For that reason we have named the enzyme the 60S kinase. An analysis of the phosphopeptide maps of acidic ribosomal proteins, phosphorylated at either the 60S kinase or casein kinase II, showed almost identical patterns. Using the immunoblotting technique, the presence of the kinase has been detected in extracts obtained from intensively growing cells. These findings suggest an important role played by the 60S kinase in the regulation of ribosomal activity during protein synthesis. PMID- 1587278 TI - Mouse liver cytidine-5'-monophosphate-N-acetylneuraminic acid hydroxylase. Catalytic function and regulation. AB - In this paper, we present the results of an investigation into the catalytic properties of CMP-Neu5Ac hydroxylase (Neu5Ac: N-acetylneuraminic acid) in high speed supernatants of mouse liver. The enzyme was most active in Hepes/NaOH pH 7.4 and was markedly inhibited by relatively small increases in ionic strength, though the inhibition was abolished by desalting procedures. Several nonionic detergents could activate the hydroxylase to various degrees in a concentration dependent manner. Ionic detergents and a number of phospholipids were, however, generally inert or inhibitory. The lack of inhibitory influence of a wide range of nucleotides revealed that CMP-Neu5Ac hydroxylase binds its sugar-nucleotide substrate with a high degree of specificity. Thus, even millimolar concentrations of several cytidine nucleotides elicited virtually negligible inhibition, though the reaction product, CMP-Neu5Gc (Neu5Gc: N-glycoloylneuraminic acid), was a weak inhibitor. The results also indicate that the enzyme is not regulated by any nucleotides or sugar-nucleotides. Dilution of high-speed supernatants with buffer gave rise to a decrease in the specific activity of the hydroxylase, implicating the involvement of more than one component in catalysis. Activity could be restored by the addition of a heat extract of the supernatant. The active principle in this extract was found to be a heat-stable protein with a molecular mass of about 17 kDa. Immunochemical studies allowed this protein to be identified as cytochrome b5 and it was shown that this electron carrier is essential for the activity of CMP-Neu5Ac hydroxylase. Inhibition studies using iron ligands and activation by exogenous iron salts suggest the involvement of a non-haem iron cofactor in the catalytic cycle of this hydroxylase. Cytochrome b5 may thus serve as an electron donor for this postulated cofactor. PMID- 1587279 TI - Sequence of horse pancreatic lipase as determined by protein and cDNA sequencing. Implications for p-nitrophenyl acetate hydrolysis by pancreatic lipases. AB - The complete sequence of the horse pancreatic lipase was elucidated by combining polypeptide chain and cDNA sequencing. Among the structural features of horse lipase, it is worth mentioning that Lys373 is not conserved. This residue, which is present in human, porcine and canine lipases, has been assumed to be involved in p-nitrophenyl acetate hydrolysis by pancreatic lipases. Kinetic investigation of the p-nitrophenyl acetate hydrolysis by the various pancreatic lipases and by the C-terminal domain (336-449) of human lipase reveals that this hydrolysis is the result of the superimposition of independent events; a specific linear hydrolysis occurring at the active site of lipase, a fast acylation depending on the presence of Lys373 and a non-specific hydrolysis most likely occurring in the C-terminal domain of the enzyme. This finding definitely proves that pancreatic lipase bears only one active site and raises the question of a covalent catalysis by pancreatic lipases. Moreover, based on sequence comparison with the above mentioned pancreatic lipases, three residues located in the C-terminal domain, Lys349, Lys398 and Lys419, are proposed as possible candidates for lipase/colipase binding. PMID- 1587280 TI - Evolutionary optimization of the catalytic efficiency of enzymes. AB - 1. The rate equation for a generalized Michaelian type of enzymic reaction mechanism has been analyzed in order to establish how the mechanism should be kinetically designed in order to optimize the catalytic efficiency of the enzyme for a given average magnitude of true and apparent first-order rate constants in the mechanism at given concentrations of enzyme, substrate and product. 2. As long as on-velocity constants for substrate and product binding to the enzyme have not reached the limiting value for a diffusion-controlled association process, the optimal state of enzyme operation will be characterized by forward (true and apparent) first-order rate constants of equal magnitude and reverse rate constants of equal magnitude. The drop in free energy driving the catalysed reaction will occur to an equal extent for each reaction step in the mechanism. All internal equilibrium constants will be of equal magnitude and reflect only the closeness of the catalysed reaction to equilibrium conditions. 3. When magnitudes of on-velocity constants for substrate and product binding have reached their upper limits, the optimal kinetic design of the reaction mechanism becomes more complex and has to be established by numerical methods. Numerical solutions, calculated for triosephosphate isomerase, indicate that this particular enzyme may or may not be considered to exhibit close to maximal efficiency, depending on what value is assigned to the upper limit for a ligand association rate constant. 4. Arguments are presented to show that no useful information on the evolutionary optimization of the catalytic efficiency of enzymes can be obtained by previously taken approaches that are based on the application of linear free-energy relationships for rate and equilibrium constants in the reaction mechanism. PMID- 1587281 TI - Isolation and partial characterization of membrane-associated cyclophilin and a related 22-kDa glycoprotein. AB - The presence of membrane-associated proteins which stereospecifically bind cyclosporin A and react with anti-cyclophilin antibodies has been documented in rat tissues. Extraction of membranes with 6 M urea or 0.5% Chaps releases cyclosporin-binding activity that is 5-12% of that found in cytosol. Cyclosporin A-binding proteins are present in most subcellular organelles of liver, but microsomes contain the greatest activity. These proteins can be purified by adsorption onto a cyclosporin-A affinity column and elution with cyclosporin A. Two major fractions are resolved on SDS/PAGE: an 18-kDa fraction is comprised of two isoforms that are similar if not identical to the two major cytosolic isoforms of cyclophilin. In addition, in microsomes an approximately equal quantity of a 22-kDa glycoprotein was detected. Based on partial sequencing (five peptides, 89 amino acids) this protein is similar but not identical to human cyclophilin B. This 22-kDa isoform is poorly recognized by affinity-purified anti cyclophilin antibodies and comprises several predominant isoforms (pI approximately 9.3-9.6). Selective binding of membrane 22-kDa cyclophilin to peanut lectin suggests the oligosaccharides contain a terminal galactosyl-N galactosamine residue. PMID- 1587282 TI - Accuracy of wheat-germ RNA polymerase II. General enzymatic properties and effect of template conformational transition from right-handed B-DNA to left-handed Z DNA. AB - We investigated the accuracy of the insertion process in RNA chain elongation catalyzed by wheat germ RNA polymerase II. Error frequencies varied from 1 misinserted nucleotide per 250 polymerized correct substrates to less than 1 in 2 x 10(5), depending on template sequence and nature of the divalent metal cofactor. Higher error ratios were observed in the presence of Mn2+ compared to Mg2+, and with alternating poly[d(G-C)].poly[d(G-C)] compared to poly[d(A T)].poly[d(A-T)]. In this latter case the eukaryotic RNA polymerase was as accurate as Escherichia coli RNA polymerase holo-enzyme. The fidelity of wheat germ RNA polymerase II was also examined in transcription of polynucleotide templates in the poly[d(G-C)] family adopting either the right-handed B or left handed Z conformations. Error ratios for noncomplementary ATP increased markedly under experimental conditions favoring the B-to-Z conformational transition of the alternating copolymers. In accordance with the results of previous studies, the rate of productive elongation, i.e. the synthesis of poly[r(G-C)], was depressed, suggesting that the decreased accuracy of the enzyme derived from an altered competence of the enzyme to form elongation complexes on the left-handed DNA. As judged by the large difference in apparent Km values of the enzyme for complementary and noncomplementary nucleoside triphosphates, part of the discrimination between substrates seemed to take place at the initial binding step. Furthermore, the results indicate that wheat germ RNA polymerase II was able to elongate a primer with a 3'-terminal mismatch, and thus to incorporate the mismatched nucleotide stably in the nascent RAN. However, the probability of productive RNA chain elongation was much lower with noncognate than with the complementary substrates. PMID- 1587283 TI - Tissue distribution of constitutive and induced soluble peroxidase in rat. Purification and characterization from lacrimal gland. AB - A thorough search for a soluble peroxidase in 31 different tissues of rat indicated the presence of a constitutive activity only in lacrimal, preputial and submaxillary gland. An induced soluble peroxidase activity was also detected in the lactating mammary gland and in the estrogen-induced uterine secretory fluid. The lacrimal gland was the richest source of the enzyme. No peroxidase activity was detected in the lactating mammary gland of mouse and hamster nor in the preputial gland of mouse and uterine fluid of hamster. The three constitutive and two induced soluble peroxidases of rat had a native molecular mass of 73 kDa by gel filtration and they showed a similar mobility in native PAGE. Lactoperoxidase of cow's milk and solubilized rat membrane-bound peroxidases of uterus, intestine and bone marrow showed in native PAGE a mobility which was distinctly different from that of rat soluble peroxidases. As the lacrimal gland of rat was the richest source of soluble peroxidase, the enzyme was purified from this gland to apparent homogeneity; SDS/PAGE then showed a single band of molecular mass 75 kDa which was similar to that obtained by gel filtration. Peroxidase also purified from preputial and submaxillary gland, as well as commercial lactoperoxidase, had a similar molecular mass on SDS/PAGE to purified lacrimal peroxidase. The visible spectrum of lacrimal peroxidase was similar to that of lactoperoxidase but different from membrane-bound peroxidase of rat neutrophils. On isoelectric focussing, purified lacrimal peroxidase resolved into about 14 multiple forms spanning a pI range of 6.5-3.5 while lactoperoxidase focussed at the cathode. Evidence presented suggests that the multiple forms are possibly due to differences in glycosylation. Immunodiffusion, immunoprecipitation and Western blot using antilacrimal peroxidase serum showed a similar interacting species for all five soluble peroxidases of rat while membrane-bound peroxidases showed no interaction. Although in immunodiffusion, the antiserum failed to cross-react with lactoperoxidase it did interact with lactoperoxidase on Western blot. The results indicate that the various constitutive and induced soluble peroxidases of rat tissues are similar to lacrimal peroxidase but are distinctly different from the known membrane-bound peroxidases of rat. However the lacrimal peroxidase shows both similarities as well as dissimilarities with bovine lactoperoxidase. This soluble peroxidase system of rat could be useful to study tissue-specific regulation of gene expression at the molecular level. PMID- 1587284 TI - Purification and characterization of the ferredoxin-glutamate synthase from the unicellular cyanobacterium Synechococcus sp. PCC 6301. AB - Ferredoxin-glutamate synthase from the unicellular cyanobacterium Synechococcus sp. PCC 6301 has been purified using, as main steps, ethanol fractionation in the presence of high ionic strength, ion-exchange chromatography and ferredoxin Sepharose affinity chromatography. The overall process yielded an homogeneous enzyme with a specific activity of 30 U/mg protein, after a purification of 2800 fold with a recovery of 43%. The molecular mass of the native protein was 156 kDa, as calculated from its Stokes radius (rS, 4.32 nm) and sedimentation coefficient (S20,w, 8.46 S). The size was also estimated by SDS/PAGE as 160 kDa, indicating that the native protein was a monomer. The enzyme exhibited absorption maxima at 279, 370 and 438 nm and a A279/A438 absorbance ratio of 11. One molecule of FMN, but not FAD, was found/molecule native protein. The addition of dithionite resulted in the loss of the absorption peak at 438 nm, which was restored by the addition of 2-oxoglutarate, thus indicating that the prosthetic group is functional in catalysis. Classical hyperbolic kinetics with substrate inhibition was seen for 2-oxoglutarate. The Km values determined for glutamine and ferredoxin were 0.7 mM and 7 microM, respectively, and the apparent Km for 2 oxoglutarate was estimated to be 1.7 mM. Azaserine and 6-diazo-5-oxo-L-norleucine were potent inhibitors of the activity, while pyridoxal 5-phosphate, known to react with Lys residues, partially inactivated the enzyme. This ferredoxin dependent glutamate synthase is, as far as we know, the first purified from prokaryotic organisms and resembles its counterpart from chloroplasts, suggesting that cyanobacterial glutamate synthase may have been the ancestor of ferredoxin glutamate synthase in plants. PMID- 1587285 TI - Eukaryotic DNA primase appears to act as oligomer in DNA-polymerase-alpha- primase complex. AB - Human placenta and calf thymus DNA-polymerase-alpha-primases were analyzed using native gradient-polyacrylamide-gel electrophoresis followed by overlay assays of polymerase and primase activities. The human enzyme contained three catalytically active native forms of 330, 440 and 560 kDa and the bovine enzyme five forms of 330, 440, 500, 590 and 660 kDa. Of the various DNA polymerase forms, only the largest (560 kDa for human DNA polymerase and 590 kDa and 660 kDa for bovine DNA polymerase) contained primase activity. Titration of human DNA-polymerase-alpha primase with DNA-polymerase-free primase caused the conversion of the 440-kDa to the 560-kDa form. The data favour the idea that primase binds to DNA polymerase alpha as an oligomer of 3 primases/polymerase core. In addition, the ability of primase to utilize oligoriboadenylates containing (prA)n or pp(prA)n was investigated. The primase elongated pp(prA)2-7 up to nanoadenylates or decaadenylates, but did not add 9 or 10 mononucleotides to a preexistent primer. In contrast to pp(prA)n less than 10, (prA)n less than 10 were rather poor primers for the primase. Both pp(prA)8,9 and (prA)n greater than 10 were elongated by primase, producing characteristic multimeric oligonucleotides. The possible connection of the structure of the DNA-polymerase-alpha-primase complex with the catalytical properties of primase is discussed. PMID- 1587286 TI - Purification and characterization of protein PC, a component of glycine reductase from Eubacterium acidaminophilum. AB - Protein PC of the glycine reductase from Eubacterium acidaminophilum was purified to homogeneity by chromatography on phenyl-Sepharose and Sepharose S. The apparent molecular mass of the native protein, which showed an associating/dissociating behaviour, was about 420 kDa. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis of protein PC revealed two protein bands corresponding to 48 and 57 kDa, indicating an alpha 4 beta 4 composition. The smaller subunit was identified as an acetyl-group-transferring protein, the 57-kDa protein was hydrophobic. N-terminal amino acid sequences were determined for both subunits. Antibodies raised against the 48-kDa subunit showed cross reactions with extracts of E. acidaminophilum grown on different substrates and with extracts from other glycine-utilizing anaerobic bacteria such as Clostridium purinolyticum, C. sticklandii, and C. sporogenes. The respective protein from the former two organisms corresponded in molecular mass. When protein PA was chemically carboxymethylated by iodo[2-14C]acetate and incubated with protein PC, acetyl phosphate was a reaction product, thus establishing it as the product of the glycine reductase reaction by using homogeneous preparations of these two proteins from E. acidaminophilum. PMID- 1587287 TI - Differential expression of the two methyl-coenzyme M reductases in Methanobacterium thermoautotrophicum as determined immunochemically via isoenzyme specific antisera. AB - Methanobacterium thermoautotrophicum contains two isoenzymes of methyl-coenzyme M reductase (MCR), MCR I and MCR II, which catalyze the methane-forming step and which together represent more than 10% of the cellular protein. We describe here the preparation of isoenzyme-specific antisera against the two MCR isoenzymes and their use in the quantitative immunochemical determination of the two isoenzymes in the methanogen. The relative and absolute cellular concentration of the two proteins is shown to be strongly affected by growth conditions such as the temperature, pH, and substrate concentration. Conditions were found yielding cells which contained essentially only MCR I or MCR II. Using antisera against MCR I and MCR II, MCR from other methanogens were immunochemically compared. Evidence is presented that Methanobacterium wolfei also contains two isoenzymes of MCR. PMID- 1587289 TI - Phase II study of mitomycin C and 5 fluorouracil in platinum resistant ovarian cancer. AB - Fourteen patients with relapsing ovarian cancer were treated with Mitomycin C (Mit C) and 5 Fluorouracil (5-FU). All but one patient (one responder) were defined as platinum resistant. The drug dosaging was Mit C 10 mg/m2 IV day 1 every 6 weeks, and 5-FU 500 mg/m2 IV days 1-3, every 3 weeks. Therapy was evaluated clinically and with ultrasound every 6 weeks. Toxicity was graded using the Gynecologic Oncology Group adverse criteria. All patients had been previously treated with platinum containing chemotherapeutic regimens with a mean cumulative total dose of 418 mg/m2 and 1308 mg/m2 of cisplatin and carboplatin, respectively. The mean time interval from completion of the last platinum containing regimen to entry in this study was 3.6 months. There were 4 responders, 1 complete, and 3 partial. The duration of the responses were 13 weeks for the complete responder, and 6, 6, and 12 weeks for the partial responders. No factor was identified which was predictive for response. Grade 3/4 granulocytopenia and thrombocytopenia were experienced by 43% and 21% of all patients respectively. Despite our documented response rate of 29%, the short duration of responses and high incidence of severe and life threatening hematologic toxicity preclude this regimen from being of any significant benefit to relapsing platinum resistant ovarian cancer patients. PMID- 1587288 TI - The quinone-reactive Ni/Fe-hydrogenase of Wolinella succinogenes. AB - The hydrogenase (Hyd) isolated from the cytoplasmic membrane of Wolinella succinogenes consists of three polypeptides (HydA, HydB and HydC) and contains cytochrome b (6.4 mumol/g protein), which was reduced upon the addition of H2. The enzyme catalyzed the reduction of 2,3-dimethyl-1,4-naphthoquinone with H2, in contrast to an earlier preparation which was made up of HydA and HydB only and did not contain cytochrome b (Unden, G., Bocher, R., Knecht, J. & Kroger, A. (1982) FEBS Lett. 145, 230-234). This suggests that HydC is a cytochrome b which serves as a mediator in the electron transfer from H2 to the quinone. The hydrogenase genes were cloned, sequenced and identified by sequence comparison with the N-termini of the three subunits. The three genes were arranged in the order hydA, hydB, hydC, with the transcription start site in front of hydA, and were present only once on the genome. Separated by an intergene region of 69 nucleotides, hydC was followed by at least two more open reading frames of unknown function. The amino acid sequences derived from hydA, hydB and hydC were similar to those of the membrane Ni-hydrogenases of seven other bacteria. HydA and HydB also showed similarity to the small and the large subunits of periplasmic Ni-hydrogenases. HydC was predicted to contain four hydrophobic segments which might span the bacterial membrane. Two histidine residues located in hydrophobic segments are conserved in the corresponding sequences of the other membrane hydrogenases and might ligate the haem B. PMID- 1587290 TI - Leukemia following cisplatin-based chemotherapy for ovarian carcinoma at Roswell Park. AB - Three cases of leukemia following cisplatin-based chemotherapy are reported. All three patients received cyclophosphamide, a known leukemogen. In two cases, the leukemia was diagnosed after second line chemotherapy with intraperitoneal cisplatin and cytarabine, one of which is the first report of a chronic granulocytic leukemia as a result of cytotoxic chemotherapy. PMID- 1587291 TI - Post-menopausal breast cancer risk: oral estrogen treatment and abdominal obesity induce opposite changes in possibly important biological variables. AB - Almost all of the epidemiological studies on the consequences of estrogen replacement treatment (ERT) refer to subjects treated with oral conjugated equine estrogens (CEE). These studies suggest that breast cancer (BC) risk is limited and can only be seen after long-term and/or high dosage use. Orally administered estrogens present a number of metabolic and endocrine peculiarities, some of which could be important in reducing the risk to the breast. Actually, these peculiarities are opposite to those observed in post-menopausal women with abdominal obesity (AO), a group which has recently been identified to be at high risk. AO (as other situations in which an increase in BC risk does exist) shows a sex-hormone-binding-globulin (SHBG) level reduction, which causes an increase of both estrogenic and androgenic activity. Further features of AO, possibly involved in BC risk, could be: i) increased free fatty acid (FFA) levels; ii) hyperinsulinemia; iii) increase of circulating insulin-like growth-factor-I (IGF I) activity. On the contrary oral estrogens, through their hepatocellular effects, cause: i) a clearcut SHBG increase; ii) a trend to reduced circulating IGF-I activity. As a consequence, the possibility that oral estrogens are characterized by a favourable balance between estrogenic activity and biological modifications protective to the breast, is worth consideration. Even non-oral estradiol have a possible protective action through FFA level reduction; however, due to the absence of hepatocellular effect, it does not influence SHBG levels and IGF-I activity. It seems difficult to extend data on the relationship between BC and oral CEE to other types of types of ERT. For the latter, further study will be necessary. PMID- 1587292 TI - 20 year follow-up on microinvasive squamous carcinoma of the cervix. AB - MISC of the cervix is a potentially fatal disease if not properly classified and treated. Strict criteria for diagnosis are required to provide appropriate therapy. It is recommended that a radical approach be considered for those patients in whom the depth of invasion of the carcinoma is greater than 3 mm on cone biopsy and in all cases where vascular invasion is demonstrated. Confluency may not of itself be a reason for more radical therapy but is an indicator of the aggressiveness of the tumor. Vascular invasion is seen more frequently with increased depth of invasion but may be found with minimal infiltration and has a serious connotation. Further refinement of the definition of MISC of the cervix appears to be needed. PMID- 1587293 TI - Pelvic lymph node metastases in cervical cancer: comparison of lymphography, inspection, radiography, and histologic examination of lymph nodes. AB - Lymphangiography is commonly performed in the pretreatment evaluation of patients with cervical carcinoma, but its value is controversial. The purpose of this report is to determine the reliability of lymphography in the indication of metastatic pelvic lymph nodes by comparing data from preoperative lymphangiography, inspection of lymph nodes during laparotomy, radiography of surgically removed lymph nodes, and postoperative histologic report. Twenty-one patients (mean age 51.1 years, SD 14.5) with cervical cancer FIGO stages I b to II b were enrolled in this study. They all underwent Wertheim's radical hysterectomy with pelvic lymphadenectomy. With reference to histologic report this series included 8 squamous carcinomas (38%), 10 adenocarcinomas (48%) and 3 sarcomas (14%). Seven patients (33%) had a positive preoperative lymphangiography, in 9 patients (43%) lymph nodes were considered positive at the inspection during laparotomy, postoperative radiography of the lymph nodes was considered probably positive in 7 patients (33%) and positive in 2 patients (10%), histologic report was positive for lymphonodal metastases in 4 patients (19%). A total of 335 lymph nodes were studied, and with reference to the evaluated methods (lymphangiography, inspection, radiography, histology), 1 positive method was found in 40 lymph nodes (12%), 2 positive methods in 6 lymph nodes (2%), 3 or 4 positive methods in none of the lymph, nodes, and 4 negative methods in 289 lymph nodes (86%). Histologic report was positive in 4 lymph nodes (1%). Lymphangiography in the pretreatment evaluation in cases of cervical carcinoma is not reliable in indicating possible metastatic lymph nodes. It remains a useful exam fixation to be routinely performed. PMID- 1587294 TI - Modifications in the psychological and behavioural structure of women after mastectomy. AB - The authors report a psychological equiry carried out by interviews and tests on mastectomised patients to find out the psycho-effective and behavioural implications related to this type of mutilation, to the type of preoperative information and to the relation with the doctor in charge, also to an eventual morphological reconstruction of the breast. They also analyse the relation between the objective result evaluated by the surgeon and the subjective evaluation of the patient. Some results of breast reconstruction are presented. PMID- 1587295 TI - Experience with recent modifications in the treatment of invasive squamous cell carcinoma of the vulva. AB - Analyzing retrospectively our results in treating 113 cases of squamous cell carcinoma of the vulva during the years 1973-1985, 5-years survival was identical with 70 per cent in 53 cases with radical vulvectomy and bilateral inguino femoral lymphonodectomy as standard therapy, as well as in 60 cases with individualized treatment. These recent modifications had better anatomic results and improved the quality of life considerably. Therefore in author's opinion standardized therapy of vulvar cancer is no longer justified. PMID- 1587296 TI - CA 125 in monitoring clinical course in ovarian cancer patients. A prospective clinical study. AB - CA 125 concentration was estimated using an immunoenzymatic test (Abbott) in sera of 130 women treated for ovarian cancer, before the treatment was started and during chemotherapy. Serum half-life of CA 125 was estimated in several of the patients after three months of chemotherapy. CA 125 serum level was found to be associated with the clinical course. Before the treatment was started, CA 125 levels showed no prognostic value as to survival but absence of a decrease in CA 125 levels after 2 to 3 months of chemotherapy was unfavourable to survival and required that alteration in treatment scheme be considered. Estimation of CA 125 half-life time after three months of treatment provided a useful prognostic index. Monitoring with the use of CA 125 levels facilitated adequate decision as to the time of performing second-look surgery. In patients with CR, who showed normal CA 125 levels at earlier stages of treatment, monitoring with the use of the marker was useless, since no elevation of CA 125 level was observed during relapse. PMID- 1587297 TI - Tumor marker CA 125 in diagnosis, monitoring management and follow-up of patients with ovarian tumors. AB - The concentration of CA 125 was defined in the blood serum of 151 patients with ovarian tumors: benign--49, borderline--5 and malignant--97. In 75.7% of benign tumors CA 125 concentrations did not exceed the normal level. In two from five patients with borderline tumors CA 125 concentration varied from 47 to 130 U/ml. High levels of CA 125 (from 125 to 10.000 U/ml and higher) were revealed in 54 from 57 patients (94.7%) with malignant ovarian tumors. If in Stages I and II elevated CA 125 levels (from 125 to 430 U/ml) were discovered in 71.4% and 80.0% of the cases, respectively, then in Stages III and IV CA 125 levels rose from 300 to 10.000 U/ml and higher in all cases. High CA 125 concentrations were noticed in 95.7% of patients with clinical signs of recurrences of the disease, and it was proved at "second-look" surgery. Thus, it was expedient to use CA 125 widely for an early detection of ovarian cancer, as a control on the efficiency of therapy and in diagnosis of subclinical recurrences of the disease. PMID- 1587298 TI - Immunohistochemical study of carcinoembryonic antigen in mucinous cystic neoplasm of the pancreas. AB - Pathologic and immunohistochemical studies of 13 patients with mucinous cystic neoplasm of the pancreas were performed in order to determine whether these lesions represent overt or latent malignancy. In 9 patients with mucinous cystadenoma, the foci of mucus-rich columnar epithelia formed the usual pattern of stratifications and papillary projections with a benign appearance and did not stain with mouse monoclonal antibody to CEA (CM-010, Mochida, Japan). In contrast, the foci of mucus-poor columnar epithelia which were in a focal distribution showed moderate to severe atypical hyperplasia and reacted strongly with anti-CEA in 6 of the 9 patients. In addition, areas of both noninvasive and invasive mucinous cystadenocarcinomas in 4 patients, which were composed primarily of mucus-poor columnar epithelia, showed diffuse cytoplasmic and/or apical reactivity with anti-CEA. Based on these results, we conclude that severe atypical epithelial hyperplasia composed primarily of mucus-poor columnar epithelia represents a precursor to mucinous cystadenocarcinoma, and, therefore, mucus-poor atypical epithelia may undergo malignant transformation. PMID- 1587300 TI - Botanical musings. PMID- 1587299 TI - Increased passage of bovine serum albumin over the respiratory tract after intratracheal instillation during septic shock in rats. AB - Sepsis may initiate acute respiratory distress syndrome which may be accompanied by an increased pulmonary epithelial-endothelial permeability. In this study, sepsis was induced by an intraperitoneal implantation of gelatine capsules containing Escherichia coli/Bacteroides fragilis/adjuvant substance. The importance of bacteria in sepsis-related lung injury was studied in rats given an intraperitoneal injection of E. coli or in rats given the adjuvant substance alone in capsules intraperitoneally. Rats with empty capsules were used as controls. The rats were intratracheally instilled with bovine serum albumin (BSA) directly after the capsule implantation or the injection of E. coli, and the passage over the lower respiratory tract was assessed as blood plasma levels of immunoreactive BSA. The plasma BSA levels in the control rats increased continuously up to 24 h after intratracheal instillation. This increase was significantly augmented already 1 h after the septic challenge, i.e. before any clinical symptoms were observed, in both the septic rats and the rats with the E. coli injected intraperitoneally. Furthermore, the time required to obtain maximal plasma BSA levels was shorter in septic, adjuvant-exposed and in E. coli-injected rats than in the controls. The plasma levels and the total BSA passage over the lower respiratory tract was significantly higher (p less than 0.001) in the septic and in the E. coli-injected rats than in the adjuvant-exposed and the control rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587301 TI - Recombinant murine interleukin 9 enhances the erythropoietin-dependent colony formation of human BFU-E. AB - Murine interleukin 9 (mIL-9) is a novel T-cell-derived lymphokine previously described as a T-cell growth factor (P40/TCGFIII) and as a mast cell growth enhancing activity (MEA). In the present study we examined the potency of recombinant (r)mIL-9 to exhibit hemopoietic growth factor activity in the human system. In semisolid cultures of normal human bone marrow-derived mononuclear cells, rmIL-9 alone at a concentration range from 25 to 200 U/ml did not reveal any colony-stimulating activity on human granulocyte-macrophage colony-forming cells (GM-CFC), erythroid colony-forming units (CFU-E), and erythroid burst forming units (BFU-E). Furthermore, we did not observe synergistic effects of rmIL-9 on the number, size, and morphological composition of human granulocyte macrophage colonies in cultures stimulated with giant cell tumor-conditioned medium. However, a synergistic effect of rmIL-9 in the human erythropoietic culture system was clearly demonstrated in the presence of recombinant human erythropoietin (rhEpo). Recombinant murine IL-9 at a concentration of 200 U/ml enhanced the number of BFU-E-derived day-14 colonies about 3.6-fold as compared to control cultures stimulated with Epo alone. The formation of CFU-E-derived day 7 colonies was not significantly altered under the same conditions. Our results demonstrate that in the presence of rhEpo, rmIL-9 is synergistically active in human bone marrow cultures as an erythroid burst-promoting factor. The development of granulocyte-macrophage colonies obviously is not affected. This finding strongly suggests that mIL-9 can mediate signals via human IL-9 receptors and further extends the range of biological activities hitherto ascribed to mIL 9. PMID- 1587302 TI - Comparison of in vivo and in vitro effects of granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with acute myeloid leukemia. AB - We studied the in vitro effects of granulocyte-macrophage colony-stimulating factor (GM-CSF) in 13 patients with acute myeloid leukemia (AML) and one patient with refractory anemia with excess of blasts in transformation using the AML blast (AML colony-forming units, AML-CFU) and mixed (granulocyte erythrocyte macrophage megakaryocyte colony-forming units, CFU-GEMM) colony culture assays. In parallel, these patients received GM-CSF s.c. at 125 micrograms/m2/day, or in escalated doses starting with 10 micrograms/m2/day for a week or until circulating blast counts reached 50 x 10(9)/liter, in an effort to sensitize leukemic blasts to cell-cycle-specific agents. Results of in vivo GM-CSF treatment were correlated with those of in vitro assays. In 9 of 12 patients (75%), GM-CSF treatment increased peripheral blood blast counts (in vivo effect). GM-CSF also stimulated in vitro AML blast colony proliferation in these nine patients and increased the S+G2M phases of the cell cycle in five out of five of these patients' samples. Two of three patients in whom an in vivo response could not be demonstrated also failed to have a detectable in vitro response. These observations suggest that the AML blast colony culture assay may be useful in predicting the response of AML to cytokine therapy. Finally, GM-CSF stimulated granulocyte-macrophage (granulocyte-macrophage colony-forming units, CFU-GM) and erythroid (erythroid burst-forming units, BFU-E) colony proliferation in 14 and 11 patients, respectively, including the 3 individuals who demonstrated no clinical effect on blast counts. It is, therefore, possible that GM-CSF may be used to stimulate proliferation of progenitors that differentiate into mature granulocyte, monocyte-macrophage, and erythroid cells. PMID- 1587303 TI - Proliferation of human hematopoietic progenitors in long-term bone marrow cultures in gas-permeable plastic bags is enhanced by colony-stimulating factors. AB - We compared the recovery of human hematopoietic progenitors in long-term bone marrow culture (LTBMC) initiated in tissue culture (TC) flasks to that in "Lifecell" bags, which are gas-permeable plastic bags in which feeder-layer cells cannot adhere. Our results showed that granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) cumulative recovery in cultures from normal donor marrow, expressed as a percent of the initial inoculum, was not statistically different in the two culture systems up to week 8, when the cultures were terminated: 31.5 +/- 19 (flask) vs 30 +/- 14 (bag) and 15.5 +/- 12 (flask) vs 11.5 +/- 8 (bag), respectively. The effects of weekly addition of recombinant human (r-hu)-interleukin 1 (IL1) and r-hu-interleukin 3 (IL3) were then studied, alone and combined, at two different concentrations. Addition of IL1, either alone or combined with IL3, in LTBMC established in flasks induced an increase of hematopoietic progenitors for the first week, but BFU-E and CFU-GM were no longer detectable at weeks 4 and 6, respectively. Analysis of adherent layer cells showed a decreased cellularity, no adipogenesis, and early disappearance of bone marrow (BM) progenitors, whereas the cycling rate of myeloid precursors, by cytosine arabinoside (Ara-C) suicide assay, was similar to that of untreated cultures. Conversely, IL3 alone (5 ng/ml) resulted in 3.6- and 5.4-fold peak increases for CFU-GM and BFU-E, respectively, at week 1 (adherent plus nonadherent cells), and the recovery of BM cells was still higher than that of control flasks at week 8. By comparison, stimulation with colony-stimulating factors (CSFs) of BM cells grown in bags never affected the longevity of the culture. Addition of IL3 (5 ng/ml) induced a higher recovery of total cells, CFU GM (range: 1.6- to 15-fold peak increase during the culture), and BFU-E (1.2- to 3-fold) compared to the untreated controls. Bags treated with IL1 alone demonstrated only transient beneficial effects, and the number of hematopoietic precursors fell below the level of control bags during the culture. IL1 and IL3 induced 1.8- and 5.3-fold peak increases in BFU-E and CFU-GM at weeks 1 and 4, respectively. Simultaneous flow cytometric analysis of CD34+/CD33+ cells and DNA content showed increased numbers and proliferation of the committed BM progenitors when CSFs were added to the bag.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1587304 TI - Characterization of Fc gamma receptors on a human erythroleukemia cell line (HEL). AB - It has been established that human platelets express a single class of Fc gamma receptors that has been designated Fc gamma RII. However, the function of this receptor on these cells and its regulation are less certain. Studies to further investigate Fc gamma RII on platelets are limited by the inability to culture platelets in vitro. Therefore, identification of a human cell line that expresses Fc gamma RII as its only Fc gamma receptor as well as other platelet characteristics would be of potential importance. To this end, we examined Fc gamma receptor expression by the human erythroleukemia (HEL) cell line, which expresses platelet/megakaryocyte surface proteins. Flow cytometry studies on HEL cells with anti-Fc gamma receptor monoclonal antibodies revealed that, similar to platelets and megakaryocytes, Fc gamma RII is the only Fc gamma receptor expressed on the cell surface. Furthermore, Northern blot analysis revealed that Fc gamma RII is the only Fc gamma receptor mRNA present. Stimulation with dimethylsulfoxide (DMSO) or 12-O-tetradecanoylphorbol-13-acetate (TPA) did not alter Fc gamma RII protein or mRNA expression. Ligand binding studies with [125I]IgG trimer indicated that HEL cells express 92,240 +/- 5030 binding sites per cell, with a kd of 1.94 +/- 0.31 x 10(-8) M. Similar to human platelets, HEL cells preferentially bound oligomeric IgG, and this binding was ionic strength dependent. These observations are similar to those previously observed with Fc gamma RII on human platelets and suggest that the HEL cell Fc gamma receptor is similar, if not identical to the platelet Fc gamma RII receptor. HEL cells may serve as a model for the study of platelet/megakaryocyte Fc gamma RII. PMID- 1587305 TI - Synergy between recombinant human IL-1 alpha (rHuIL-1) and M-CSF (rHuM-CSF) during the recovery of murine hematopoietic activity in myelosuppressed animals: abbreviated versus chronic administration of rHuM-CSF. AB - The ability of highly purified, recombinant human macrophage colony-stimulating factor (M-CSF) and recombinant human interleukin 1 alpha (IL-1) to rescue hematopoietic activity from the myelosuppressive effects of 5-fluorouracil (5-FU) was investigated in the C57Bl/6 mouse. IL-1 (q24 h x 4) stimulated granulopoietic recovery in the 5-FU-treated animals and reduced the period of severe neutropenia associated with this drug by 7 days. Chronic M-CSF administration (q24 h x 14), on the other hand, resulted in a modest retardation of granulocyte recovery, and, when combined with IL-1, the chronic administration of M-CSF significantly dampened the accelerated recovery of granulopoietic activity observed with IL-1 alone. Consistent with their effects on neutrophil recovery, IL-1 alone markedly enhanced the recovery of the granulocyte erythrocyte macrophage megakaryocyte colony-forming units (CFU-GEMM), macrophage colony-forming units (CFU-M), and erythroid burst-forming units (BFUe) in the marrow, whereas M-CSF failed to demonstrate a significant influence on the restoration of these hematopoietic progenitors (with the exception of delaying the recovery of the BFUe). Unexpectedly, the combination of IL-1 plus M-CSF (q24 h, days 1-4) followed by M CSF (q24 h, days 5-14) resulted in a more than additive stimulation of progenitor recovery in both the marrow and the spleen that was observed as early as day 3 following 5-FU treatment. Furthermore, in the absence of protracted M-CSF administration on days 5-14, the 4-day rescue with a combination of IL-1 plus M CSF also resulted in a more than additive effect on the recovery from 5-FU induced neutropenia. Collectively, these observations demonstrated that IL-1 and M-CSF can interact synergistically to stimulate granulopoietic recovery in the 5 FU-treated animal. However, the data also suggest that the continued administration of M-CSF following the 4-day IL-1 plus M-CSF rescue may interfere with the restoration of neutrophils in the myelosuppressed animal. PMID- 1587306 TI - Iron modulates interferon-gamma effects in the human myelomonocytic cell line THP 1. AB - This investigation demonstrates that low concentrations (25 microM) of free and transferrin-bound iron reduce the efficiency of the interferon-gamma (IFN-gamma) signal in the human myelomonocytic cell line THP-1, as seen by decreased production of neopterin, reduced degradation of tryptophan, and impaired expression of major histocompatibility complex (MHC) class II antigens. This inhibitory effect of iron, which is not due to an enhanced cytotoxicity towards THP-1 cells, is increased by enhancement of iron concentrations in a dose dependent relationship and can be partially reversed by increasing amounts of the cytokine. The iron-mediated inhibition of the effects of IFN-gamma is fully reversed when iron is administered concomitantly with equimolar concentrations of the iron chelator deferoxamine. Furthermore, deferoxamine alone is even able to enhance the efficiency of the IFN-gamma signal. Our data provide evidence that there is an inverse correlation between the intracellular amount of iron, which is not bound to ferritin, and the activity of the IFN-gamma signal. This suggests that iron withholding by the immune cells in the course of inflammatory disorders may also contribute to the enhancement of the cytopathic effect of IFN-gamma. This speculation is confirmed by the observation of high concentrations of immune activation markers such as IFN-gamma and neopterin and low serum iron levels in patients with hypoferric anemia in the course of chronic inflammation. PMID- 1587307 TI - Accelerated recovery of peripheral blood cell counts in mice transplanted with in vitro cytokine-expanded hematopoietic progenitors. AB - Interleukin 1 (IL-1) and interleukin 3 (IL-3) act synergistically in stimulating the growth of primitive hematopoietic progenitors. Murine bone marrow (BM) harvested 24 h after 5-fluorouracil (5-FU) administration (d1 5-FU BM) was stimulated with IL-1 and IL-3 to expand its progenitor pool during 7 days of suspension culture (delta-culture), and this in vitro expanded BM was compared to fresh d1 5-FU BM in its ability to reconstitute lethally irradiated or high-dose 5-FU-treated hosts. Transplantation with expanded delta-culture BM was found to dramatically shorten the period of cytopenia following lethal irradiation as compared to animals receiving d1 5-FU BM. Recipients of delta-cultured BM demonstrated accelerated recoveries of peripheral blood leukocytes, neutrophils, platelets, and erythrocytes. Furthermore, expansion of BM in vitro reduced the number of BM cells required for engraftment following lethal irradiation. Treatment of lethally irradiated mice with IL-1 and granulocyte colony stimulating factor (G-CSF) following transplantation with delta-cultured BM or d1 5-FU BM further improved the recovery of neutrophils in these hosts. In conjunction with G-CSF post-transplantation cytokine therapy, high-dose 5-FU treated mice transplanted with delta-cultured BM also demonstrated improved recovery kinetics of neutrophils and erythrocytes. Five and 10 weeks after BM transplantation, a decrease in the proliferative capacity of the earliest hematopoietic progenitors, detected in assays of primary and delta-culture generated-secondary high proliferative potential colony-forming cells (HPP-CFC), was found in all transplanted mice following a chemotherapy challenge with 5-FU. However, this impairment in the early progenitor/stem cell pool was not noticeably worsened by the expansion of BM in delta-cultures. The decrease in host hematopoietic proliferative potential associated with transplantation of limiting numbers of BM cells was not reversed over the 10 weeks of this study. The expansion of BM progenitor cells without loss of long-term proliferative potential may be of clinical importance in the fields of BM transplantation and gene therapy. PMID- 1587308 TI - Transient expression of the IL-2 receptor alpha-chain in IL-6-induced myeloid cells is regulated by autocrine production of prostaglandin E2. AB - The alpha-chain of the interleukin 2 receptor (IL-2R alpha) is expressed on monocytes and macrophages after activation by bacterial lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). In the present study, we investigated whether the expression of IL-2R alpha is associated with the process of differentiation of myeloid cells to mature macrophages and how this expression is regulated. The murine myeloid M1 cell line, which can be induced by leukemia inhibitory factor (LIF) or interleukin 6 (IL-6) to differentiate from blast cells to mature macrophages, was used as a model system for myeloid differentiation. Bone marrow (BM)-derived macrophages were used as mature myeloid cells. Cytofluorometry revealed that IL-2R alpha is transiently expressed during M1 cell differentiation, with peak levels 24 h after induction by LIF or IL-6, whereas the high affinity receptor for monomeric IgG2a (FcR), a surface marker typical for macrophage differentiation, continues to rise up to 72 h. BM-derived macrophages already express FcR but not IL-2R alpha. IL-2R alpha expression is induced on these cells after treatment by IL-6 for up to 48 h. Treatment of IL-6 induced M1 cells with indomethacin permitted a sustained expression of IL-2R alpha beyond 24 h, and this effect was reversed by the addition of prostaglandin E2 (PGE2). Northern analysis showed that in M1 cells the expression of mRNA for IL-2R alpha, but not for IL-2R beta, is also transient, indicating that cell surface expression of IL-2R alpha is regulated at the mRNA level. These data show that inducers of macrophage differentiation such as LIF and IL-6 can induce a transient expression of the IL-2R alpha-chain in differentiating murine myeloid M1 cells and that autocrine production of PGE2 is involved in the control of the transient expression of this receptor. However, induction of expression of IL-2R alpha by IL-6 appears to be independent of differentiation because it can be induced on fully differentiated BM-derived macrophages as well. PMID- 1587309 TI - Rapid protein tyrosine phosphorylation selectively induced in murine responsive ELM-I-1 cells by erythropoietin. AB - We investigated whether protein tyrosine phosphorylation was induced by erythropoietin (Epo) in two murine Epo-responsive cell lines (ELM-I-1, which proliferates autonomously and is induced to differentiate by Epo, and DA-1ER, which grows in a manner dependent on Epo or interleukin-3 (IL-3) without differentiation). In ELM-I-1, Epo induced the tyrosine phosphorylation of a protein of about 80-85 kDa (py80) which appeared in the Triton-X soluble fraction of the cell lysate in a time- and concentration-dependent manner. Maximal levels of phosphorylation were obtained within 5-10 min at Epo concentrations above 0.1 U/ml. IL-3 is known to promote the proliferation of this cell line, but it did not induce py80 phosphorylation. In DA-1ER, tyrosine phosphorylation of py80 was not induced by either Epo or IL-3. These findings suggest that there are multiple pathways of Epo signaling and that one of them could be via tyrosine kinase activation. Furthermore, it is possible that the tyrosine phosphorylation of py80 is involved in the pathway leading only to erythroid differentiation but not to cellular proliferation. PMID- 1587310 TI - Bioavailability of iron. PMID- 1587311 TI - Otto Detlev Creutzfeldt, 1927-1992. PMID- 1587312 TI - Tonic activity of rat medial vestibular nucleus neurones in vitro and its inhibition by GABA. AB - The spontaneous discharge of 48 medial vestibular nucleus (MVN) neurones was recorded extracellularly in horizontal slices of the rat brainstem in vitro. The mean tonic rate of discharge was 17.1 +/- 8.2 imp/s, similar to that observed by others in transverse (coronal) slices of the rat and guinea pig MVN. The tonic rate of discharge of individual MVN cells either increased or decreased after synaptic blockade in low Ca2+ media, suggesting that ongoing synaptic activity has an important influence on the spontaneous activity of MVN cells in vitro. However the persistence of tonic activity after synaptic blockade indicates that an intrinsic, pacemaker-like mechanism is involved in the generation of the tonic activity. GABA, muscimol, baclofen and 3-APA inhibited the tonic activity of all MVN cells tested. Bicuculline antagonised, and picrotoxin blocked, the inhibitory responses to muscimol, but the effects of GABA were only partially blocked in 50 microM picrotoxin. The effects of baclofen and 3-APA persisted in low Ca2+ media, and were antagonised by saclofen and phaclofen. Picrotoxin-resistant responses to GABA persisted in low Ca2+ media, and were also antagonised by saclofen. These results suggest that the inhibitory control of MVN neurones by GABA involves both the GABAA and GABAB subtypes of GABA receptor. GABAB receptors appear to be distributed both pre- and post-synaptically in the rat MVN. The possible significance of the intrinsic, tonic activity of MVN cells in normal vestibular function and in vestibular compensation, and the effects of GABA, are discussed. PMID- 1587313 TI - Single-unit activity in the globus pallidus and neostriatum of the rat during performance of a trained head movement. AB - Single-unit extracellular neuronal recordings were obtained from the globus pallidus (GP) and the neostriatum (NS) of rats while they performed a learned head movement in response to an auditory cue. In both GP and NS, units that altered their discharge rate in association with head movements and with the cues that triggered these head movements were prevalent. Frequently, the responses were directionally-specific (i.e., the magnitude or direction of change in firing rate of these neurons was substantially different for trials in which head movements were made to the left vs. the right). For some units, firing rates were altered only in response to the movement cue or only in association with head movements. However, the majority of neurons exhibited responses with both cue related and movement-related components. Neuronal responses to the auditory cue usually were context-dependent, in that they did not occur if the same stimulus was presented when the animal was not performing the task. At least a small proportion of GP and NS neurons also appeared to exhibit context-dependent movement-related activity, in that responses occasionally were observed that were associated either with sensory-triggered head movements or with spontaneous head movements, but not with both. These data are consistent with previous suggestions that the activity of basal ganglia neurons during movement performance is highly dependent on the conditions associated with movement initiation. The data also indicate that the response characteristics of both GP and NS neurons in the rat are generally similar to those that have been described for basal ganglia neurons in primates and cats during sensory-triggered movement tasks. However, the proportion of task-related neurons that exhibited responses with both movement related and cue-related components was greater than has generally been reported in studies of cats and primates, suggesting that neurons with these response properties may be more predominant in the rat basal ganglia. PMID- 1587314 TI - Chronic infusion of GABA into the nucleus basalis magnocellularis or frontal cortex of rats: a behavioral and histological study. AB - In order to determine the influence of the nucleus basalis magnocellularis (NBM) on the sensorimotor function of the frontal cortex (FCx) of the rat, GABA at various concentrations (10, 50 or 100 micrograms.microliters-1) was administered into these structures. GABA was infused for four consecutive days after which saline was infused for another four. On the contralateral side the order of administration was reversed. Each structure received GABA while its homologous on the contralateral side received saline. Before, during and after drug infusion, the animals were weighted and their performance in two non-reinforced behavioral tasks (beam walking and spontaneous rotation) was examined. When GABA was infused into the FCx, a dose-dependent and reversible sensorimotor deficit was observed along with a behavioral withdrawal syndrome upon GABA discontinuation. When GABA was administered into the NBM, a reversible sensorimotor deficit was observed only when GABA was infused at the highest concentration. In this case no behavioral changes were observed upon GABA discontinuation. Histologically, a gliosis was observed in the NBM in which GABA was infused at the two highest concentrations without saline pretreatment; these effects were not observed when GABA was infused without saline pretreatment into the FCx. In relation to our previous findings, these results suggest that i) the FCx is directly involved in the expression of sensorimotor functions, while the influence of the NBM on these functions appears only after severe subcortical damage, ii) a GABA withdrawal syndrome is observed following GABA administration in the FCx but not in the NBM, and iii) "tonic" effects of GABA are dose-related and partially dependent upon pretreatment conditions and the brain region infused. PMID- 1587315 TI - Sensory responses of intralaminar thalamic neurons activated by the superior colliculus. AB - The intralaminar thalamus of anesthetized rats was explored for neurons activated by stimulation of the superior colliculus and responsive to sensory inputs. Neurons activated by stimulation of the intermediate and deep collicular layers were distributed throughout the intralaminar thalamus. Approximately one half of them responded to tectal as well as sensory inputs. The majority were nociceptive or had a more complex response pattern including responses to auditory stimulation. A small population of low threshold units had contralateral orofacial receptive fields and responded to light taps; these units were preferentially localized anteriorly in the central lateral and paracentral nuclei. Neurons responsive to tectal and sensory stimulation were randomly intermingled with other neurons which had no detectable sensory input. The results indicate that ascending projection neurons of the intermediate and deep layers of the superior colliculus provide an input to functionally diverse subpopulations of intralaminar thalamic neurons. In view of its projections to motor cortex and basal ganglia, the intralaminar thalamus appears directly implicated in basal ganglia and superior colliculus related mechanisms of attention, arousal and postural orienting. PMID- 1587316 TI - Dorsal column input to thalamic VL neurons: an intracellular study in the cat. AB - This study investigated the role of the ventral lateral (VL) nucleus of the thalamus as a lemniscal relay to motor cortex. Intracellular recordings were obtained from thalamic VL relay neurons in cats anesthetized with chloralose, following stimulation of the dorsal column nuclei. VL neurons were identified by their short-latency input from the cerebellar nuclei, their antidromic activation from motor cortex and their anatomical location. A total of 105 neurons was studied. The occurrence of temporal facilitation to double volleys was also examined. It was found that 80/105 (75%) neurons responded with excitation and/or inhibition to stimulation of the dorsal column nuclei. The latencies of the postsynaptic responses ranged from 2.0 to 20 ms (median 10.0 ms). The latencies of nearly all responses (79/80) were greater than 3 ms and nearly all responses (45/47) which were tested for it, displayed temporal facilitation to double shock stimulation, consistent with polysynaptic transmission. Effective stimulation sites were found in the gracile and cuneate nuclei. Recording sites were located throughout VL, including the "border region" with the ventral posterior lateral nucleus (VPL). There was no obvious topographic relationship between location of recording site and latency or polarity (excitation versus inhibition) of the synaptic responses. This is consistent with dorsal column input diffusely distributed over VL. When the recording electrodes penetrated VPL, characteristics of the EPSPs were indicative of monosynaptic transmission (short latency, no temporal facilitation). This clear transition from VL to VPL suggests that it is not necessary to define, on physiological grounds, a separate "border region" between these two nuclei.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587317 TI - Longterm impairment of cat optokinetic nystagmus following visual cortical lesions. AB - Binocular and monocular gain of optokinetic nystagmus (OKN), OKN dynamics, vestibulo-ocular reflex (VOR) and VOR adaptation were measured in 5 normal cats and in 5 cats which underwent bilateral visual cortical lesions involving the 17 18 complex at least 4 months before testing. We observed longterm deficits after bilateral lesions involving area 17 and variable parts of area 18 but failed to observe deficits after 18-19 lesions. These deficits were limited to the OKN gain and the build-up time constant of OKN; the VOR and the optokinetic after nystagmus (OKAN) time constant were within normal limits. Our results suggest that areas 17-18 operate in parallel to control the encoding of retinal slip velocity at the level of the nucleus of the optic tract (NOT) and the accessory optic system (AOS), which are known to represent the initial stage of the optokinetic pathways. PMID- 1587318 TI - A comparison of intact and in-vitro locomotion in an adult amphibian. AB - Locomotion was compared in an intact and in-vitro preparation of the adult mudpuppy (Necturus maculatus). The intact animals walked on an aquatic treadmill while in-vitro preparations were made to walk with a bath application of the excitatory amino acid NMA (N-methyl DL-aspartate). EMG recordings of shoulder muscles (pectoralis, latissimus dorsi, dorsalis scapulae, and procoracohumeralis) and elbow muscles (brachialis and extensor ulnae) were obtained from intact animals while recordings were made from only the elbow muscles in-vitro. The in vitro preparation required magnesium in the bath to initiate and maintain locomotion, consistent with an NMDA mediated response. Also consistent with an NMDA response was the finding that glycine potentiated the NMA induced locomotion in-vitro. The range of cycle durations seen in-vitro was well within the range seen in the intact animal, while gait analysis demonstrated the similarity of intact and in-vitro locomotor cycles. In spite of these very similar locomotor patterns there are interesting differences in the patterned output seen in-vitro, such as the absence of a second burst in the brachialis muscle in-vitro. PMID- 1587319 TI - Spread of synaptic activity along parallel fibres in cat cerebellar anterior lobe. AB - 1. Mossy fibre evoked activity in the cerebellar cortex elicited by peripheral electrical stimulation was studied in chloralose anesthetized cats. The distribution of intracortical field potentials in the C3 and D zones was mapped in order to determine if there is a spread of synaptic activity outside the mossy fibre termination area. This area was identified by the presence of short latency synaptic field potentials in the granular layer. 2. Molecular layer field potentials were recorded up to 1.5 mm outside the mossy fibre termination area. The latencies of these potentials increased with increasing distance from the mossy fibre termination area, corresponding to a conduction velocity of about 0.4 m/s. 3. Recordings from Purkinje cells, within and outside the mossy fibre termination area, revealed an increase of simple spike activity at latencies corresponding to those of the field potentials in the same location. 4. From the spatial and temporal characteristics of the evoked activity, it is concluded that a mossy fibre input results in spread of synaptic activity along the parallel fibres. 5. The findings are discussed in relation to the recently discovered microzonal organization of the C3 zone. It is proposed that the organization of this zone offers a possibility for the control of muscle synergies, each synergy being represented by a mossy fibre input and the specific set of microzones activated by this input via the parallel fibres. PMID- 1587320 TI - Cerebellar cortex and eyeblink conditioning: a reexamination. AB - We examined the effects of cerebellar cortical lesions upon conditioned nictitating membrane responses in rabbits. Using extended postoperative conditioning and unpaired presentations of the conditioned stimuli (CSs), we confirmed that combined lesions of lobules HVI and ansiform lobe abolished conditioned responses (CRs) established to light and white noise CSs. Extended retraining enabled some slight recovery of CR frequencies. Less extensive cortical lesions produced initial abolition of CRs but allowed more complete recoveries. Although CR frequencies and amplitudes were profoundly depressed by cortical lesions, unconditioned response (UR) amplitudes to periorbital electrical stimulation were enhanced. The dissociation of lesion effects upon conditioned and unconditioned responses is consistent with the suggestion that cerebellar cortical mechanisms are important for the learning and execution of eyeblink conditioning. PMID- 1587321 TI - Somatosensory evoked potential correlates of psychophysical magnitude estimations for air-puff stimulation of the face in man. AB - Air-puff stimuli were applied to the skin of the face to obtain psychophysical and neurophysiological responses. Six levels of stimulus intensity above threshold were adopted for numerical magnitude estimation and for recording somatosensory evoked potentials (SEPs). A power function with an exponent of 0.71 provided an adequate description of the magnitude estimation values as a function of stimulus intensity, as was verified by the high correlation coefficient (r = 0.86, P less than 0.001). Six SEP components (N15, P20, N30, P40, N50 and P65) were recorded during the 100 ms following stimulation. Stimulus-amplitude functions of the various SEP components were well represented by power functions. The P20-N30 component had the highest power exponent (0.66) and also the highest correlation coefficient (r = 0.55, P less than 0.001). The SEP latencies as a function of stimulus intensity had negative power functions. The latency function of the P20 component had the largest negative power exponent (-0.10) and showed the highest negative correlation (r = -0.62) with the stimulus intensity. These results suggest that processing of intensity information occurs at a relatively early stage within the central nervous system, and that both the amplitude and latency information encoded in the SEPs may contribute to stimulus processing. PMID- 1587322 TI - Input-output relation of the somatosensory system for mechanical air-puff stimulation of the index finger in man. AB - This study examined input-output relation of the somatosensory system in response to mechanical air-puff stimuli applied to the volar aspect of the tip of the index finger. Compound sensory nerve action potentials (SNAPs) from the median nerve at the wrist and cerebral somatosensory evoked potentials (SEPs) were simultaneously recorded at six levels of stimulus intensity above threshold. Using the time-integral of the SNAPs and SEPs as measures of peripheral and central neural activity, a strongly accelerating power function with an exponent of 1.35 was found to describe peripheral neural function, while central neural function was described by a negatively accelerating function with a power exponent of 0.50, suggesting suppression of SEPs by recruitment of units with increasing stimulus intensity. It was concluded that input-output relation of the somatosensory system can be described by a decelerating power function with the exponent of 0.37. PMID- 1587324 TI - Influences of hand movements on eye movements in tracking tasks in man. AB - We investigated horizontal smooth pursuit eye movements and hand movements in tracking tasks in order to find out whether hand movements influence eye movements and if so, in what ways. Externally controlled target movements were tracked either by the eyes alone or by the eyes and right hand together. Because a possible influence might depend on the stimulus, we used two classes of target movements: sinusoidal target movements (predictable target movements) and pseudo random target movements (unpredictable target movements). Our data show that the eye movements contained only a few small saccades when sinusoidal target movements with frequencies higher than about 1 Hz were tracked by eyes and hand together. More and larger saccades were made when the same target movements were tracked by the eyes alone. The difference in smoothness of eye movements was highly significant between the two tracking conditions. Such a difference was not found during the tracking of a pseudo-random target motion. This suggests that the influence of hand movements is related to the predictability of the stimulus. In contrast to the gain of the smooth pursuit eye movements and the maximum of the cross-correlation function, the gain of the composite eye movements did not depend on the tracking condition. The delay of the eye movements with respect to the (sinusoidal) target movements also showed no dependence on the tracking condition. Visual feedback from the tracking hand was found not to play a role in the difference in eye movements for the two tracking conditions. PMID- 1587323 TI - Central facilitation of Ia inhibition during tonic ankle dorsiflexion revealed after blockade of peripheral feedback. AB - Recent studies have reported that no increase of the disynaptic reciprocal inhibition can be observed during tonic voluntary dorsiflexion of the foot as compared to rest, when the size of the control H-reflex is kept constant. Other studies have, however, shown that a voluntary contraction evokes a strong and long-lasting depression of the synaptic transmission from Ia afferents to motoneurones, most likely secondary to activation of these afferents during the contraction (post-activation depression). It was thought that this effect could also interfere with the demonstration of a central facilitation of the reciprocal inhibition during movement. The amount of disynaptic Ia reciprocal inhibition from the pretibial flexors to the soleus H-reflex was therefore estimated in normal human subjects at rest and during voluntary tonic dorsiflexion before, during and after blocking the peripheral feedback from the investigated muscles. It was observed that the reciprocal inhibition measured during dorsiflexion increased during occlusion of the blood supply to the leg, reaching a maximum of inhibition after 30 min of ischaemia. After release of the ischaemia the inhibition gradually decreased to its pre-ischaemic level. It is therefore suggested that the brain facilitates transmission in the Ia disynaptic reciprocal pathway during tonic voluntary dorsiflexion of the foot, but that this facilitation is normally not observed due to a post-activation depression following the peripheral feedback activation during the movement. PMID- 1587325 TI - Kinematic models and human elbow flexion movements: quantitative analysis. AB - The smoothness with which movements are customarily performed has led Hogan (1984) to formulate a model for trajectory planning by the central nervous system in which the goal is to maximize smoothness, one measure of which is the integrated mean squared magnitude of jerk (jerk cost). We tested the applicability of this minimum-jerk model to one-joint goal directed movements performed by human subjects at different speeds and amplitudes, by comparing kinematic parameters and the jerk cost predicted by the mathematical model with values calculated from experimental data. We also tested a higher order, minimum snap kinematic model. Normal subjects performed elbow flexions of 5 to 50 degrees "as rapidly and accurately as possible" and also at slower speeds. The boundary conditions of both models were adjusted to account for the failure of subjects to produce movements which reached equilibrium precisely at the target (so that acceleration and velocity reached zero together). Typically, fast movements (less than 300 ms duration) were fairly symmetric in that the durations and amplitudes of acceleration and deceleration were approximately equal; slower movements (greater than 300 ms) were asymmetric with strong, brief acceleration peaks and broad, slow deceleration peaks. In fast movements, the calculated jerk cost was consistently higher than predicted by the minimum-jerk model; a good fit to all kinematic parameters was provided by the minimum-snap model (a seventh-order polynomial). Neither model consistently predicted the trajectories of slower movements. We conclude that muscle/limb dynamics can account for the success of the minimum-snap model with fast movements, and that there is no evidence of planning for maximal smoothness in slower movements. PMID- 1587327 TI - Three-dimensional drawings in isometric conditions: relation between geometry and kinematics. AB - Normal human subjects grasped a 3-D isometric handle with an otherwise unrestrained, pronated hand and exerted forces continuously to draw circles, ellipses and lemniscates (figure-eights) in specified planes in the presence or absence of a 3-D visual force-feedback cursor and a visual template. Under any of these conditions and in all subjects, a significant positive correlation was observed between the instantaneous curvature and angular velocity, and between the instantaneous radius of curvature and tangential velocity; that is, when the force trajectory was most curved, the tangential velocity was lowest. This finding is similar to that obtained by Viviani and Terzuolo (1982) for 2-D drawing arm movements and supports the notion that central constraints give rise to the relation between geometric and kinematic parameters of the trajectory. PMID- 1587326 TI - Coordination between posture and movement in a bimanual load lifting task: putative role of a medial frontal region including the supplementary motor area. AB - The aim of the present experimental series was to investigate the role of the medial frontal region including the supplementary motor area in the coordination between posture and movement in a bimanual load lifting task. The seated subject was instructed to maintain in a horizontal position one forearm (postural arm) which was loaded with a 1 kg weight. The unloading was performed either by the experimenter (imposed unloading) or by a voluntary movement of the other arm (voluntary unloading). In normal individuals, with the voluntary unloading, the movement control was accompanied by an anticipatory adjustment of the postural forearm flexor activity, which resulted in the maintenance of the forearm position despite the unloading. The anticipatory postural adjustments were impaired in 4 out of 5 patients with unilateral lesion of the SMA region; the defect was observed mainly when the postural forearm was contralateral to the lesion. No change in the anticipatory postural adjustment was observed in one patient with complete callosal section. This finding indicates that the coordination between the posture and movement in this task is not organized through callosal fibers linking the cortices on both sides but rather at a subcortical level. The anticipatory postural adjustments were abolished in two patients with spastic hemiparesis when the postural forearm was the spastic arm. It is suggested that the SMA region contralateral to the postural forearm, together with other premotor or motor areas, may select the circuits responsible for the phasic postural adjustments which are necessary to ensure postural maintenance, whereas the motor cortex contralateral to the voluntary movement controls both the movement and, via collaterals, the preselected circuits responsible for the associated postural adjustments. PMID- 1587328 TI - Regeneration by skeletomotor axons in neonatal rats is topographically selective at an early stage of reinnervation. AB - The seven sectors of the rat's serratus anterior (SA) muscle are innervated topographically by motor neurons of spinal cord segments C6 and C7 whose axons travel in the long thoracic (LT) nerve. That pattern is roughly mapped early in development and gains its final precision postnatally. The segmentotopic pattern is reestablished better in neonates than adults after cutting the LT nerve. We examined the process of reinnervation to see whether segmental selectivity is reestablished at the outset or whether it arises by rearrangement of the regenerated axons. Recordings were made from muscle fibers 1 to 70 days following a cryogenic lesion of the LT nerve done within 48 h of birth, as well as from sham-operated and unoperated control rats. Reinnervation of all sectors of SA occurred within a week after freezing the nerve. Reinnervation by C6 and C7 motor neurons was topographically selective though not quite to the degree found in controls. The precision observed during the first week of reinnervation did not improve over the next 9 weeks. Thus, selectivity exists from the start rather than being a more random reinnervation subsequently sharpened by elimination of inappropriate connections. The number of muscle fibers innervated by both C6 plus C7 motor neurons was greater after reinnervation than in controls. There was a significant decrease in the percentage of these dually innervated fibers over the initial few weeks of reinnervation but there was no difference among the reinnervated sectors of SA. Reinnervation of SA under optimal conditions resembles normal development in that there is a degree of topographic selectivity of (re)innervation that is present even at the earliest time periods studied. Unlike normal development the topographic selectivity after neonatal reinnervation does not improve over time, and fibers receiving a dual segmental innervation are not preferentially located in sectors where there is the most overlap in segmental projection. PMID- 1587329 TI - Recovery and loss of muscle force of rat plantaris after partial denervation. AB - The isometric contractile characteristics of rat plantaris muscles were assessed 1, 3, 6, 9, and 12 months after resection of the L4 radicular nerve. After 1 month of partial denervation, twitch and tetanus were significantly lower (26.1 and 22.1%, respectively) than those of sham-operated rats. Plantaris muscle weight was reduced (22.5%), but twitch-to-tetanus ratio (TW/TT), time-to-peak, and one-half relaxation time were not changed significantly. At 3 months, average twitch force was normal but average tetanic force was significantly lower (27.1%) than control value. Muscle weight was reduced (28.9%), but TW/TT was increased by 31%. After 6 months, twitch, tetanus, and all other variables were similar to those of control rats. Normal twitch at 3 months indicates that all muscle fibers have been reinnervated by sprouting from L5 motor axons; however, the new synaptic contacts may not support the tetanic response. At 9 months, muscle force was again reduced and remained at about the same level at the 12-month interval. These results are consistent with the recovery and loss of function seen in poliomyelitis and the postpolio syndrome. PMID- 1587330 TI - Long-term effects of partial denervation on sprouting and muscle fiber area in rat plantaris. AB - The long-term effects of partial denervation on the muscle fiber cross-sectional area, degree of axonal sprouting, and end-plate morphology were examined 1, 3, 6, 9, and 12 months postsurgery in rat plantaris muscle. After 1 month of partial denervation, mean cross-sectional areas of type I and type II myofibers were significantly lower than that of sham-operated controls; fiber atrophy and hypertrophy was observed. After 3 months, we found no statistical difference in the mean cross-sectional fiber area between the two experimental groups. After 6 months, the fiber areas were now significantly larger than controls, possibly the result of compensatory work hypertrophy, due to the overuse of remaining hyperexpanded motor units. Preterminal, intranodal, and intraterminal sprouting were found to significantly increase from 1 to 6 months following partial denervation. While sprouting was enhanced, the number of terminal branch points per end plate did not change. Following 9 months of partial denervation and overuse, the mean fiber areas significantly decreased as compared to controls. The former muscles were found to contain angulated fibers, group atrophy, and increased levels of axonal sprouting. The number of terminal branches per end plate was now significantly increased over control values, possibly a compensatory response to reduced synthesis of neurotrophic factor(s) and/or transmitter-related components. At 12 months, fiber areas, axonal sprouting, and the number of terminal branches per end plate have all decreased. Degenerating end plates, denervated myofibers, angulated fibers, and group atrophy were observed. It would appear that aging-like changes are occurring earlier in chronically stressed, partially denervated muscles. PMID- 1587331 TI - Local cerebral glucose utilization during chronic infusion of GABA into the nucleus basalis magnocellularis of rats. AB - The metabolic effects of gamma aminobutyric acid (GABA) unilaterally infused for 24 h into the nucleus basalis magnocellularis (NBM) of rats were studied using the 2-deoxyglucose method for measuring local cerebral metabolic rates for glucose (CMRglc). These results demonstrated that GABA infusion at the concentration of 100 micrograms.microliters-1 induced a strong ipsilateral depression in glucose utilization in the NBM and in some surrounding structures (e.g., the lateral hypothalamic area, thalamus, and amygdala) as well as in the major cortical targets of NBM neurons (i.e., the frontal, parietal, and temporal cortices). On an other hand, GABA infusion at the concentration of 10 micrograms.microliter-1 had no significant effect on cerebral metabolism compared to the saline-infused rats. Nevertheless, both GABA at the concentration of 10 micrograms.microliter-1 and saline induced a reduction of cerebral metabolism in the infused NBM, compared to the contralateral noninfused NBM. It was also demonstrated that saline pretreatment reduced the metabolic depression induced by GABA infusion at the highest concentration. When GABA was infused at the concentration of 100 micrograms.microliter-1, a slight reduction of CMRglc was observed in the hemisphere contralateral to the infused one, mainly in NBM target areas. In view of our previous behavioral data, these results suggest among others, that there is no necessary relationship between cerebral glucose metabolism and behavioral expression. PMID- 1587333 TI - Synaptic reorganization in the feline ventral anterior thalamic nucleus induced by lesions in the basal ganglia. AB - This report presents the results of quantitative analysis of synaptic coverage of the dendrites of thalamocortical projection neurons in the adult cat ventral anterior thalamic nucleus (VA) and its changes at short (4 days)- and long-term (1 year) survival times after combined unilateral kainic acid lesions in the substantia nigra pars reticularis and entopeduncular nucleus. The study showed that deafferentation induced an increase in the appositional length of the dendrites of GABAergic local circuit neurons along projection neuron dendrites, accompanied by an increase in the number of dendrodendritic synapses. Dendritic or axonic origin of other unusual presynaptic structures at 1 year postlesion could not be established with certainty. All of them displayed some features of growth cones, such as an abundance of tubular and vesicular structures many with electron-dense contents. Projection neuron dendrites postsynaptic to these profiles contained numerous coated vesicles at the same survival time. The findings suggest that (i) the lesioning of the two basal ganglia output structures induces synaptic reorganization in the VA, (ii) this process appears to be active at 1 year after deafferentation, and (iii) all reactive systems display symmetric contacts and positive GAD immunoreactivity suggesting that homotypic remodeling is taking place. Despite the signs of remodeling, the density of presynaptic terminals with symmetric contacts on primary and secondary projection neuron dendrites in the VA remained below the control level at 1 year postlesion suggesting that an imbalance of excitatory and inhibitory inputs on thalamocortical projection neurons may persist for long periods after deafferentation. PMID- 1587332 TI - (-)Deprenyl increases activities of superoxide dismutase and catalase in striatum but not in hippocampus: the sex and age-related differences in the optimal dose in the rat. AB - The dose of (-)deprenyl (2.0 mg/kg/day, sc, for 3 weeks) which significantly increased activities of superoxide dismutase (SOD) and catalase in the striatum of young male rats significantly reduced these activities in young female rats but did not change the SOD activity in old female rats. In order to clarify these effects, different doses of the drug were continuously infused sc for 3 weeks in three groups of rats (young males and young and old females). When a 10-fold smaller dose (0.2 mg/kg/day) was applied in young female rats, activities of both SOD and catalase were significantly increased, while a higher dose of 0.5 mg/kg/day was ineffective and a lower dose of 0.1 mg/kg/day was substantially less effective. In old female rats, doses of both 0.5 and 1.0 mg/kg/day were equally effective in elevating activities of SOD and catalase, while a lower dose of 0.1 mg/kg/day was less effective. The activity of glutathione peroxidase (GSH Px) remained unchanged in all groups, except for a significant decrease in the activity of non-selenium-dependent GSH Px in both young and old female rats given the highest drug dose (2.0 mg/kg/day). Furthermore, activities of all three enzymes remained unchanged in the hippocampus in most groups. The results indicate that (-)deprenyl significantly increases activities of both SOD and catalase in the striatum, but not in hippocampus of rats, and that the optimal dose is very different depending on the sex and age of the animal. PMID- 1587334 TI - Effects of spinal cord transection and MK-801 on CGRP immunostaining in the rat urinary bladder. AB - Numerous studies have demonstrated that lesions in the CNS can alter the density of sensory nerve processes in peripheral organs. In the present study, rat spinal cords were transected at the second lumbar segmental level and the density of calcitonin gene-related peptide (CGRP)-immunoreactive nerve fibers in the urinary bladder was examined. Additional rats had spinal cord transections followed by 12 days of treatment with the N-methyl-D-aspartate receptor antagonist, MK-801. In the bladders of control rats, CGRP-immunoreactive fibers were present as thick nerve trunks, perivascular plexi, and a fine meshwork of varicose nerve fibers. Twelve days following a spinal cord transection, the density of CGRP immunoreactive nerve fibers was markedly reduced; occasional fibers appeared primarily as nonvaricose fine fibers. In bladders from rats receiving a spinal cord transection and MK-801 treatment, CGRP-immunoreactive fibers were abundantly distributed throughout the detrusor muscle; these fibers exhibited numerous varicosities as well as some enlarged terminal varicosities. These data demonstrate that (i) an upper motor neuron-type lesion markedly decreases the density of CGRP-immunoreactive peripheral afferent nerve processes and (ii) following a spinal cord transection, MK-801 appears to enhance the density of CGRP immunostaining in the bladder. PMID- 1587335 TI - Changes in polyamine levels and spectrin degradation following kainate-induced seizure activity: effect of difluoromethylornithine. AB - The induction of ornithine decarboxylase (ODC) in adult CNS and the resulting changes in polyamine levels are often observed under conditions associated with activation of NMDA receptors, calpain stimulation and spectrin degradation. The present study was directed at evaluating the links between these two sets of events. We measured the effects of an acute treatment of adult rats with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, on biochemical alterations following kainate-induced seizure activity. Beside ODC activity and polyamine levels, we assayed the in situ spectrin degradation and the in vitro binding of 3H-Ro5-4864, a ligand for the peripheral benzodiazepine binding sites which is a good marker of glial proliferation, at various time intervals following systemic kainic acid (KA) injection. Kainate-induced seizure activity was followed by a transient increase in ODC activity, a long-lasting increase in putrescine levels and spectrin degradation, and a delayed increase in 3H-Ro5-4864 binding, mainly in hippocampus and piriform cortex. Treatment of the animals with DFMO markedly reduced the increase in putrescine levels up to 7 days after KA injection. It also reduced the increase in spectrin breakdown observed at 16 h but not at 4 and 7 days after KA injection. Finally, it did not modify the increase in 3H-Ro5-4864 binding measured 4 and 7 days after KA injection. The levels of putrescine were positively correlated with the extent of spectrin proteolysis in KA-treated animals whether or not they were treated with DFMO, at 16 h but not at 7 days after KA injection. The results indicate that the extent of spectrin breakdown observed shortly after KA-induced seizure activity is causally related to the changes in ODC activity and putrescine levels. Although the data are consistent with the idea that putrescine could be a marker for acute pathology, they do not support a role for polyamines in delayed neurotoxicity. PMID- 1587336 TI - Phase resetting and frequency entrainment of essential tremor. AB - Step and sinusoidal forcings were delivered to the wrists of 10 patients with advanced essential tremor using a computer-controlled torque motor. Consistent (type 0) phase resetting was produced in only 5 patients, whereas all 10 patients exhibited harmonic and 2:1 subharmonic entrainment of essential tremor. These results indicate that the oscillator of essential tremor is coupled to the stretch-reflex arc. Irregularity in the tremor rhythm and postperturbation mechanical-reflex oscillations obscured the phase of essential tremor, thereby impeding the computation of phase resetting curves. Sinusoidal forcings circumvented these problems, but frequency entrainment was produced only by forcings at frequencies within +/- 1 Hz of the tremor frequency and its second harmonic. Resonance accompanied frequency entrainment and probably plays a role in the clinical expression of tremor. PMID- 1587337 TI - Collagen synthesis in an established liver connective tissue cell line (GRX) during induction of the fat-storing phenotype. AB - We have studied collagen synthesis and secretion in an established liver connective tissue cell line (GRX) that can be induced in vitro to express either the myofibroblastic or the fat-storing (lipocyte) phenotype. In lipocytes, collagen synthesis was reduced. Their intracellular collagen degradation corresponded to 15% of newly synthesized collagen. In myofibroblasts, collagen synthesis was high but its secretion was considerably altered by intracellular collagen degradation, which attained up to 60% of newly synthesized collagen. In this in vitro model, we have provided direct evidence that hepatic lipocytes, involved mainly in lipid and retinol metabolism, have a low basal level of collagen synthesis. Myofibroblastic phenotype correlates with increased collagen synthesis and may be directly related to increased collagen deposition in hepatic fibrosis. Modulation of the phenotype of liver connective tissue cells are possibly one of the major points of control in normal and pathological deposition of collagen in liver parenchyma. PMID- 1587338 TI - The pituitary in cirrhosis: ultrastructure, growth hormone, and prolactin concentrations. AB - Micronodular cirrhosis was induced in male SUAH substrain Wistar rats by combined phenobarbitone and carbon tetrachloride treatment. Both pituitary and serum concentrations of growth hormone were significantly reduced in cirrhotic rats compared with age-related untreated rats or those treated only with phenobarbitone. Ultrastructurally growth hormone-secreting cells (somatotrophs) of pituitaries of cirrhotic rats appeared relatively inactive, having few hormone containing granules, sparse rough endoplasmic reticulum, and small nuclei with areas of condensed chromatin. The cells themselves were smaller than similar cells of untreated rats with a reduced cytoplasmic area. In addition immunocytochemistry of pituitaries at light microscope level, using sheep anti rat growth hormone antibody, showed that somatotrophs of cirrhotic rats were more heteromorphic and disorganized than those in controls. There was marked development of the folliculo-stellate cell system in pituitaries of cirrhotic rats, the cells were enlarged with distinct golgi, and numerous microvilli were projecting into dilated follicular lumena. PMID- 1587339 TI - Extracellular matrix contraction by cultured mesangial cells: modulation by transforming growth factor-beta and matrix components. AB - Cultured glomerular mesangial cells (MCs) have the ability to contract the surrounding collagen gel matrix (CGM). To investigate this phenomenon, we examined the effect of growth factors and extracellular matrix (ECM) components. Among some growth factors tested, transforming growth factor-beta (TGF-beta) and fetal calf serum (FCS) enhanced CGM contraction dose dependently. These factors acted through distinct mechanisms because: (1) when growth-arrested MCs were used, the effect of FCS was inhibited partially but that of TGF-beta was not; and (2) anti-TGF-beta had no influence on CGM contraction induced by FCS. Among the ECM components such as laminin, fibronectin, type IV collagen, and heparin-like proteoglycans (heparan sulfate and heparin), which were each mixed separately with CGM before gelling, heparin-like proteoglycans and type IV collagen inhibited contraction by MCs. The inhibitory effect of heparin was mediated by the interaction both with CGM and with MCs because: (1) when heparin was added to the culture medium, not into the gel, the inhibitory effect was diminished but still noted; and (2) using growth-arrested MCs, the inhibitory effect of heparin in the medium was reduced but still observed. This culture assay is useful for elucidating the tensional interaction between MCs and surrounding ECM. PMID- 1587340 TI - Neurotoxicity of dichlorvos: effect on antioxidant defense system in the rat central nervous system. AB - The effect of dichlorvos exposure (5 mg kg-1 body wt, ip) on lipid peroxidation and antioxidant defense system in different regions of the rat central nervous system was studied. In the present paper an inhibition of acetylcholinesterase activity was used as an index of dichlorvos neurotoxicity. We observed significant increases in the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase which were accompanied by a decrease in the values of lipid peroxidation. Dichlorvos exposure also resulted in a significant decrease in glutathione peroxidase activity. The decreased levels of both reduced and oxidized glutathione as observed on dichlorvos exposure affected the GSH/GSSG ratio. These results indicate that the enzymes SOD and catalase may enhance the disposal of potentially toxic radicals. Furthermore, the decrease in GSH levels may be a mechanism for the detoxification of dichlorvos in the brain. PMID- 1587341 TI - Impaired vascular reactivity following angioplasty is mainly due to endothelial injury. AB - Vasoconstriction occurs frequently following coronary angioplasty and is implicated in the pathogenesis of abrupt closure and restenosis. Control of vasomotor tone is regulated in part directly by smooth muscle cells and indirectly through the endothelium. To study the mechanisms underlying vasoconstriction, the effect of angioplasty and endothelial denudation on endothelium-dependent and -independent relaxation was examined in 15 mongrel dogs. Percutaneous transluminal angioplasty and endothelial denudation of the right femoral artery were performed. Endothelial injury was assessed by adhesion of indium-111-labeled platelets. Endothelium-dependent and -independent relaxation were assessed using acetylcholine and nitroglycerin, respectively. Vessels precontracted with potassium chloride and exposed to acetylcholine showed impaired relaxation in both the angioplasty and denuded groups (angioplasty = 14 +/- 5%, denuded = 0 +/- 0%, normal = 73 +/- 12%; P less than 0.05 for both angioplasty and denuded compared to normal). Precontraction with phenylephrine yielded similar results (angioplasty = 16 +/- 8%, denuded = 4 +/- 2%, normal = 39 +/- 10%; P less than 0.05 only for denuded segment compared to normal). Segments precontracted with phenylephrine and exposed to nitroglycerin did not demonstrate impaired relaxation (angioplasty = 73 +/- 9%, denuded = 68 +/- 9%, normal = 71 +/ 7%, P = ns). Mean indium-111 counts were similar in both the angioplasty and denuded segments (2820 +/- 1481 and 2963 +/- 1228 counts/min/g, respectively) compared to a lower count in the normal segment (1514 +/- 956 counts/min/g). Thus, angioplasty produces significant vascular injury and impairment of vasodilator function, comparable to that caused by endothelial denudation alone. This implies that vasoconstriction seen following coronary angioplasty may be due to endothelial injury and the resultant loss of control of vasomotor tone. PMID- 1587342 TI - Lung collagen synthesis and deposition in tight-skin mice with genetic emphysema. AB - The tight-skin (Tsk) mouse is a genetic model of pulmonary emphysema linked to a deficiency of serum antielastase. In this mouse occurrence of connective tissue abnormalities in various organs (systemic scleroderma) has been reported. The aim of the present work was to study lung collagen synthesis and deposition in Tsk mice. No differences in the collagen synthesis rate and morphology at the ultrastructural level were found in Tsk mice at birth. At 2 months of age, a marked increase in collagen was observed within the alveolar septa. At this time, an increased lung collagen synthesis, assessed by determining prolyl hydroxylase activity and incorporation of radiolabeled proline, was found in Tsk mice with respect to control mice. However, due to the ongoing parenchymal destruction, the values of total lung collagen at 6 and 12 months of age were only moderately but significantly increased with respect to those observed at 2 months. As a consequence, a progressive accumulation of lung collagen fibers was observed in the residual septa. The increase in collagen deposition was accompanied by a relative increase in type I collagen. Although the data in the literature would suggest a genetic cause for the lung collagen change in Tsk mice, the data presented here indicate that the change in lung collagen metabolism may be a part of a remodeling process taking place after lung destruction. PMID- 1587343 TI - Type-specific changes in fiber morphometry following denervation of canine extraocular muscle. AB - To investigate the changes that occur in extraocular muscle morphometry following denervation, 12 beagles were subjected to intracranial section of the left oculomotor nerve. The inferior and medial rectus muscles were removed from both orbits of four dogs killed at each 4-week postoperative interval. Fiber diameters and fiber-type ratios of denervated muscles were compared with those from paired muscles in the normal orbit. We found significant, persistent atrophy of the singly innervated fibers in both the global and orbital layers of denervated extraocular muscle. The multiinnervated fibers were predominantly spared from denervation atrophy. We also found a significant increase in the proportion of multiinnervated fibers in the orbital layer only. These results suggest a relative neurotrophic independence of multiinnervated fibers in extraocular muscle. PMID- 1587344 TI - Index of biochemical reviews. 1990. PMID- 1587345 TI - Pseudouridine in the large-subunit (23 S-like) ribosomal RNA. The site of peptidyl transfer in the ribosome? AB - On evolutionary grounds, it has been advocated for more than 40 years that RNA generally, and more recently rRNA in particular, may participate, catalytically, in protein biosynthesis. A specific molecular mechanism has never been proposed. We suggest here that the N-1 position(s) in one or more of the approximately 4 pseudouridine (omega) residues in E. coli 23 S rRNA catalyzes transfer of the aminoacyl moiety from teh 3'-terminus of peptidyl tRNA in the P site to aminoacyl tRNA in the A site of the ribosome. Evidence that supports the proposal in the case of E. coli ribosomes, and relevant information pertaining to eukaryotic ribosomes, is summarized. Essential features of the evidence are that (i) the N-1 position in 1-acetylthymine (a direct analogue of 1-acetylpseudouridine) has an especially high potential for acyl-group transfer, comparable to that found for N acetylimidazole (Spector, L.B. and Keller, E.B. (1958) J. Biol. Chem. 232, 185 192), (ii) most of the omega residues in prokaryotic 23 S rRNA are confined to the peptidyl transferase center in E. coli ribosomes, and (iii) Um-Gm-omega, the most densely modified sequence in eukaryotic 26 S rRNA, is universally conserved at a fixed site in the putative peptidyl transferase center of all eukaryotic ribosomes. PMID- 1587346 TI - Assembly and processing of subunit II (PsaD) precursor in the isolated photosystem-I complex. AB - The precursor of photosystem I (PSI) subunit II (pre-subunit II) synthesized in vitro, was found to bind to the holo-PSI complex, both within the thylakoids and outside, after detergent extraction of PSI from the membranes. Chloroplast stromal fraction added to the purified PSI complexes, containing the labeled pre subunit II, induced the processing of the precursor to the mature form. This implies that processing can occur within the isolated complex, after the integration of the precursor. The results presented suggest that certain aspects of biogenesis of membranal protein complexes can be studied in detergent extracted purified complexes. PMID- 1587347 TI - C-CAM (Cell-CAM 105) is a calmodulin binding protein. AB - C-CAM (Cell-CAM 105) is a transmembrane cell adhesion molecule belonging to the immunoglobulin superfamily. It mediates intercellular adhesion of rat hepatocytes and occurs in various isoforms in several epithelia, vessel endothelia and leukocytes. We now report that purified liver C-CAM interacts specifically with calmodulin. Binding was observed both when 125I-labeled C-CAM was used in a dot blot assay and when 125I-labeled calmodulin was used in a gel overlay assay. Experiments with protease-generated peptides indicated that calmodulin bound to the cytoplasmic domain of C-CAM. Analyses of whole liver membranes demonstrated that C-CAM is one of five major proteins that bind calmodulin in a calcium dependent manner. PMID- 1587348 TI - Cloning of a bovine voltage-gated K+ channel gene utilising partial amino acid sequence of a dendrotoxin-binding protein from brain cortex. AB - Several variants of fast-activating, voltage-dependent K+ channels exist in the nervous system where they control cell excitability and synaptic transmission, some of which are blocked selectively by alpha-dendrotoxin. Cloning of a K+ channel from bovine genomic DNA was achieved using a primer based on the N terminal sequence of the larger subunit from the purified toxin acceptor, in conjunction with secondary primers, in the polymerase chain reaction. The resultant amino acid sequence is highly homologous to RCK 5 already cloned from rat brain, which yields a K+ current susceptible to alpha-dendrotoxin, when expressed in oocytes. These findings establish conclusively that the extensively characterized alpha-dendrotoxin acceptor is a K+ channel protein. PMID- 1587349 TI - Up-regulation of interleukin (IL)-6 receptor gene expression in vitro and in vivo in IL-6 deprived myeloma cells. AB - Myeloma cells absolutely require interleukin-6 (IL-6) for growing in vivo in patients with multiple myeloma and exogenous IL-6-dependent myeloma cell lines have been reproducibly obtained. In this study we show a dramatic up-regulation of the IL-6 receptor (gp80 chain) gene expression in myeloma cell lines following the removal of exogenous IL-6. Such a regulation was also known to occur in IL-6 deprived myeloma cells in vivo in three patients who were treated with optimal doses of anti-IL-6 monoclonal antibodies. The direct effect of IL-6 on IL-6 receptor gene expression in myeloma cells was further confirmed by adding IL-6 to an autonomously growing myeloma cell line. PMID- 1587350 TI - Recognition of an antiparallel beta-sheet structure of human epidermal growth factor by its receptor. Site-directed mutagenesis studies of Ala-30 and Asn-32. AB - The Ala-30 and Asn-32 residues involved in the major antiparallel beta-sheet structure of human epidermal growth factor (hEGF) were substituted with various amino acid residues, and the receptor-binding affinities of the nine variant hEGFs were determined by the use of human KB cells. The Ala-30----Arg, Ala-30--- His and Ala-30----Phe substitutions drastically reduced the binding affinity, suggesting that the side chain in position 30 of Ala-30 of hEGF is required to be small for the receptor binding. The Asn-32----Asp substitution significantly reduced the binding affinity, while the Asn-32----His variant could bind to the receptor as well as to the wild-type hEGF. Therefore, it seems to be important for receptor binding that the side chain in position 32 does not have a negative charge but does have an NH group. Thus, we propose that, in the ligand-receptor complex, the receptor recognizes, on one side of the antiparallel beta-sheet structure of hEGF, a wider contact area than previously suggested. PMID- 1587351 TI - Basic fibroblast growth factor (bFGF) in rodent testis. Presence of bFGF mRNA and of a 30 kDa bFGF protein in pachytene spermatocytes. AB - We have previously described a 30 kDa basic fibroblast growth factor (bFGF)-like protein in rodent testicular homogenates and have shown that pachytene spermatocytes are the sites of predominant immunoreactivity for this bFGF-like protein (Mayerhofer, A., Russell, L.D., Grothe, C., Rudolf, M. and Gratzl, M. (1991) Endocrinology 129, 921-924). We have now addressed the question whether this 30 kDa bFGF-like protein is a large bFGF form and whether it is produced by pachytene spermatocytes. We detected bFGF mRNA in homogenates of isolated mouse spermatocytes (which consisted mainly of pachytene spermatocytes) using S1 nuclease protection assays. As shown by Western blot analyses, the bFGF mRNA in mouse spermatocytes is translated into bFGF of an approximate molecular weight of 30 kDa. Neither bFGF mRNA, nor bFGF itself, was observed in isolated mouse Leydig cells. These results indicate that the immunoreactive bFGF-like protein observed previously in germ cells of the murine testis is identical to bFGF. Thus, germ cells of the testis produce bFGF, which may exert regulatory function in the process of spermatogenesis. PMID- 1587352 TI - The influence of the target structure on the efficiency of alkylation of single stranded DNA with the reactive derivatives of antisense oligonucleotides. AB - Site-directed alkylation of three oligonucleotide targets: 41-mer (hairpin structure), 22-mer (loop part of this hairpin) and 10-mer (part of the loop) with 5'-p-(N-2-chloroethyl-N-methylamino)benzylamides of oligonucleotides complementary to the loop region was studied. Thermodynamic parameters of the interaction were estimated using the dependence of the limit modification extent on the reagent concentration at several temperatures. The stability of the complex increases significantly in the set: 302-mer carrying above hairpin, 41 mer, 22-mer, the data for 22-mer and 10-mer being nearly identical. This indicates significant influence of the loop supporting structure on the interaction with antisense reagents. PMID- 1587353 TI - Murine ST2 gene is a member of the primary response gene family induced by growth factors. AB - The murine ST2 gene, which encodes a protein remarkably similar to the extracellular portion of murine interleukin 1 receptor types 1 and 2, is expressed in growth-stimulated BALB/c-3T3 cells in the presence of 50 micrograms/ml of cycloheximide. The treatment with 1,000 U/ml of purified native murine beta-interferon superinduced, rather than suppressed, the ST2 mRNA expression as in the cases of c-myc and JE mRNAs. These results suggested that the murine ST2 gene belongs to the family of primary response genes induced by growth factors. Furthermore, a longer ST2-related mRNA was found in BALB/c-3T3 cells that were stimulated to proliferate in the presence of cycloheximide. PMID- 1587354 TI - A comparative study of the relationship between thermostability and function of phenylalanyl-tRNA synthetases from Escherichia coli and Thermus thermophilus. AB - The relationship between thermostability and functional activities of phenylalanyl-tRNA synthetases (EC 6.1.1.20) from E. coli and Thermus thermophilus has been studied. In the case of the E. coli enzyme, the activity decreased after the 43 degrees C treatment, both in the [32P]PPi-ATP exchange reaction and the overall aminoacylation reaction, due to thermo-inactivation of the phenylalanyl tRNA synthetase, whereas tRNA(Phe) preserved its native structure. In the Th. thermophilus system, the enzyme showed extreme thermostability (up to 90 degrees C), and the reduction in the tRNA aminoacylation rate after the 78 degrees C treatment was ascribed to denaturation of the tRNA(Phe). Since the enzyme did not lose the [32P]PPi-ATP exchange activity up to 85 degrees C, the observed lower thermo-resistance of the tRNA is evidence that the native structure of ribonucleic acids should be one of the most difficult to stabilize at high temperatures. PMID- 1587355 TI - The path of a protein chain can be approximated by the conformation dictated by interpeptide ionic bridges. AB - A stereochemical simulation of the formation of ionic bridges between adjacent peptide groups along the polypeptide chain has been made. Such ionic bridges constrain the amino-acid residues into eight conformations. It is shown that the path of any protein-chain fragment 10-15 residues long can be approximated well by these conformations. This suggests that the conformations dictated by the ionic bridges can be used as blocks in the formation of the spatial protein structure. PMID- 1587356 TI - Kinetic analysis of translocation into isolated chloroplasts of the purified ferredoxin precursor. AB - Time courses of the import into isolated chloroplasts of the purified ferredoxin precursor were measured at different protein concentrations. Analysis of the initial import rates indicates the presence of one saturable import system with an apparent Km value of approximately 100 nM and a Vmax corresponding to the uptake of approximately 2.5 x 10(4) precursor proteins per minute per chloroplast. We conclude that the in vitro observed activity of the chloroplast protein import machinery, functioning independently from cytosolic factors, would be enough to allow chloroplast development at physiological rate. PMID- 1587357 TI - Purification of the 28.5 kDa cytosolic protein involved in the activation of NADPH oxidase from guinea pig neutrophils. AB - We tried to purify a new protein component required for the activation of NADPH oxidase from the guinea pig neutrophil cytosolic fraction which did not contain p47phox and p67phox, using HAC-5CP, IEC-QA and Superose 12HR columns. The NADPH oxidase-activating activity was separated into three fractions on IEC-QA anion exchange HPLC. However, when each of the fractions was purified by Superose 12HR gel filtration, the active fraction eluted at the same position, and was found to contain a common protein with a molecular weight of 28.5 kDa on SDS-PAGE. These results suggest that the 28.5 kDa protein is a novel NADPH oxidase activating protein. PMID- 1587358 TI - Cellobiose oxidase of Phanerochaete chrysosporium enhances crystalline cellulose degradation by cellulases. AB - The effect of Phanerochaete chrysosporium cellobiose oxidase (CBO) on microcrystalline cellulose hydrolysis by Trichoderma cellulases was determined. Addition of 10 micrograms.ml-1 CBO to a reaction mixture containing T. viride cellulase increased glucose and cellobiose production by 10% and 48%, respectively. Cellulose weight loss was also enhanced by 19%. At higher concentrations (20-80 micrograms.ml-1), CBO decreased glucose and cellobiose production. Cellulose weight loss at 60 micrograms.ml-1 CBO was 76% compared to control cellulase reactions. This decrease appears to be due to inactivation of cellulase by H2O2 produced via CBO reaction, because addition of catalase enhances sugar production and cellulose weight loss. These findings suggest that at low, perhaps physiologically relevant concentrations, CBO enhances crystalline cellulose degradation by cellulases. PMID- 1587359 TI - Left-handed topology of super-secondary structure formed by aligned alpha-helix and beta-hairpin. AB - A novel super-secondary structure common for many non-homological proteins is considered. This folding pattern, consisting of adjacent along the chain alpha helix and beta-hairpin, has an aligned packing. It is found that one of the two possible 'mirror-symmetrical' topologies is observed in proteins. The alpha-helix + beta-hairpin structures have a similar pattern of hydrophobic residues in their amino acid sequences. The remaining part of a molecule or a domain is almost always located on the same side of the considered folding pattern. These results can be used in the prediction of three-dimensional protein structure and protein design. PMID- 1587360 TI - A Ca(2+)-dependent protein kinase phosphorylates phosphoenolpyruvate carboxylase in maize. AB - In C4 plants the activity of phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) is regulated by phosphorylation/dephosphorylation which is mediated by light/dark signals. The study using protein kinase inhibitors showed that the inhibition pattern of maize PEPC-protein kinase (PEPC-PK) is similar to that of myosin light chain kinase, a Ca(2+)-calmodulin-dependent PK. The kinase activity was also inhibited by EGTA and the inhibition was relieved by Ca2+. These results suggest that PEPC-PK is Ca(2+)-dependent in contrast with previous observations by other research groups. PMID- 1587361 TI - Design, synthesis and solution structure of a renin inhibitor. Structural constraints from NOE, and homonuclear and heteronuclear coupling constants combined with distance geometry calculations. AB - A macrocyclic renin inhibitor was designed using molecular modeling and a model of human renin. The synthesized molecular displayed poor binding affinity. To investigate the reasons for the observed inactivity, the structure of the compound has been studied by NMR spectroscopy and distance geometry. Structural constraints for distance geometry calculations were derived from nuclear Overhauser effects and homonuclear and heteronuclear three bond coupling constants. Homonuclear coupling constants were measured directly from the resolution-enhanced proton spectra and heteronuclear coupling constants were measured from the natural abundance 15N- and 13C-edited TOCSY experiments. One phi angle was determined uniquely by this method and two were reduced to two possible values each. By using a statistical analysis of 400 structures generated with distance geometry, two families of structures were found to be consistent with the NMR data. The solution structures so derived were different from the originally designed structure, including an internal hydrogen bond. This provides a possible explanation for the lack of effectiveness of this compound. PMID- 1587362 TI - Endometriosis. PMID- 1587363 TI - Environmental influence on human reproduction. PMID- 1587364 TI - Ethical problems in gynaecology and obstetrics. PMID- 1587365 TI - Inequity in reproductive health: the challenge to obstetricians/gynaecologists. PMID- 1587366 TI - AIDS in women. PMID- 1587367 TI - Nasal septum deformity in the newborn infant during labour. AB - The incidence of nasal septum dislocation (NSD) was studied in 447 newborns and was found to be 17%. The aim of this study was to establish its aetiology as well as to find ways of prevention and early diagnosis of this obstetrical injury. The following conclusions were drawn: (a) The high frequency of NSD is due to the inadequate support technique (Playfair manoeuvre) currently in use. This is true even when birth weight is normal or less than normal. (b) The severity of injury is lessened by the degree of experience of the obstetrician. This is why NSD is characterised as an obstetrical injury. (c) NSD to the right is more frequent in the front left position of occipital presentation. (d) NSD is more frequent in the anterior part of the nose because the injury is sustained by the anterior part of the septum. (e) The frequency of NSD was not higher in classical forceps delivery, in caesarean section, and in spontaneous delivery. (f) No statistically significant correlation was found between the duration of expulsion and nasal septum dislocation (chi 2 = 4.43, p greater than 0.1). Due to present conditions, a general rhinological examination of all neonates is necessary. The use of Metzenbaum's sign (asymmetry of nostrils) and Jeppesen and Windfeld's test (pressure on the tip of the nose), along with rhinoscopy are recommended. Early diagnosis and treatment of NSD is of great importance, since all complications arising from this obstetrical injury can be prevented and normal function of the nose restored. PMID- 1587368 TI - The predictive value of fetal heart rate monitoring: a retrospective analysis of 2165 high-risk pregnancies. AB - The predictive value of fetal heart-rate monitoring on fetal well-being was studied in 2165 high-risk pregnancies. 1883 reactive nonstress test (NST) patterns and 278 nonreactive NST patterns and 4 cases of sinusoidal pattern were obtained. Oxytocin challenge test (OCT) was applied to 263 nonreactive cases. OCT was not applied to 15 cases out of 278 nonreactive NST cases, because of placenta previa, abruptio placenta and previous cesarean section. There were 155 cases with negative OCT, 84 cases with positive OCT and 24 cases with equivocal, prolonged or severe variable decelerations. Sensitivity and specificity were for NST 50 and 88% and for OCT 60 and 67%. The positive and negative predictive values were 11 and 98% for NST and 18 and 93% for OCT. It is concluded that the reactive nonstress test is a reliable test for good outcome but a positive oxytocin challenge test is not a reliable test for poor outcome. Additional procedures are necessary such as assessment of fetal growth, doppler velocity waveforms and fetal biophysical profile to avoid unnecessary obstetric interventions and to reach good fetal outcome. PMID- 1587369 TI - FHR monitoring and perinatal mortality in high-risk pregnancies. AB - The aim of the study was to evaluate the effect of the introduction of fetal heart rate monitoring on perinatal mortality rates in high-risk pregnancies. Results were compared with the perinatal mortality rates published previously from our clinics. The study group consisted of 2165 high-risk pregnant patients. The perinatal mortality rate in the study group was 28.6%, and the corrected rate 15.9%. The rates were significantly lower in comparison with the total perinatal mortality rates in former years. We are convinced that fetal heart-rate monitoring resulted in a significant decrease in the perinatal mortality rate. Although the increased use of fetal monitoring cannot reduce perinatal mortality resulting from problems such as genetic disorders, this study shows improved outcomes for many high-risk conditions, in particular postmature pregnancies. PMID- 1587370 TI - Ultrasound diagnosis of complete abortion can reduce need for curettage. AB - One hundred and fifty-five patients presenting with signs of incomplete abortion were evaluated by ultrasound. Of these, 112 (72.26%) were found to have retained products of conception and were treated by dilatation and curettage. The remaining 43 (27.74%) were found on ultrasound to have no products of conception and were followed-up conservatively. Only one of the latter group of patients needed admission later for dilatation and curettage; this patient was found to have a small sub-mucus fibroid and endometritis. Predictive value for those not requiring D & C was 97.6%, suggesting that this test may be useful in identifying those patient who have had a complete abortion. PMID- 1587371 TI - Vulvovaginal candidiasis refractory to treatment with fluconazole. AB - We present the case of an infertile patient, whose first attempt at IVF had to be postponed for 18 months due to a vulvovaginal yeast infection refractory to treatment. The main causative organism was a Candida glabrata strain resistant to all the imidazolic agents tested. The organism and the host's humoral status were studied in depth, looking for possible causes of the refractoriness to treatment. PMID- 1587372 TI - Probable pancreatic cancer in a pre-eclamptic patient. AB - We report a patient in the third trimester of pregnancy, suffering from pre eclampsia with HELP syndrome criteria as well as from a pancreatic neoplasm. PMID- 1587373 TI - Hypertension in pregnancy. PMID- 1587375 TI - Prevalence of minor congenital anomalies in newborns of diabetic mothers. AB - Minor congenital anomalies (MCA) were assessed in the offspring of 802 gestational diabetic mothers, 117 pre-gestational diabetic mothers, and 380 offspring born to normal mothers. The prevalence of infants with MCA ranged between 19.4% and 20.5% in the three groups without any significant difference between them. There was no correlation between the prevalence and type of MCA and the severity of the diabetic state. Neither was there any correlation between the prevalence or type of MCA and the appearance or type of major congenital anomalies. PMID- 1587374 TI - Serum antibodies to Chlamydia trachomatis in women with ectopic pregnancy, normal pregnancy or salpingitis. AB - Serum antichlamydial antibodies were studied in three groups. Group A included 49 women with recent ectopic pregnancy, group B included 56 women with normal first trimester pregnancy, and group C included 20 women with a first episode of acute salpingitis. In the ectopic pregnancy group, a significantly higher percentage of women had IgG antichlamydial antibodies than in the normal pregnancy group (75.5% vs. 46.4%, P less than 0.001). Women with acute salpingitis had the same prevalence of IgG antibodies as patients who had an ectopic pregnancy (60% vs. 75.5%, P less than 0.10). In the ectopic pregnancy group, the women had a significantly higher geometric mean titer (GMT) of antichlamydial IgG antibodies than women with an intra-uterine pregnancy (70.4% vs. 27.3%, P less than 0.001). The results suggest that there is a positive relation between prior Chlamydia trachomatis infection and risk for tubal pregnancy. PMID- 1587376 TI - Endometrial morphology and hormonal profiles in in vitro fertilization patients. AB - Endometrial biopsy was performed in 27 infertile women participating in the IVF program. Their mean age was 31.8 years, 33% of the women being over 35 years old. The average duration of infertility was 6.9 years. The superovulation protocol consisted of hMG/hCG in 5 cases, of combined GnRH analog/gonadotropin therapy in 20 women, and 2 patients received combined contraceptive pill/gonadotropin treatment. Judging by hormonal profiles, follicular growth rate and number of oocytes retrieved, the response to stimulation was normal. The mean estradiol (E2) levels increased from 132.7 pg/ml on day -5 (SEM = 9.67) to 1272 pg/ml (SEM = 103.7) on the day of hCG administration and to 1813 pg/ml (SEM = 209.6) 1 day later. One day before the hCG application, the mean progesterone and LH levels were 1.34 ng/ml and 8.38 IU/ml, respectively. Only one patient had clinical hyperstimulation syndrome. Ova were harvested in all women, the mean number of oocytes being 7.7 (SEM = 0.83) per patient. In all 27 cases lack of fertilization or faulty ovum cleavage were observed. Thus, an endometrial biopsy (EB) was performed 72 h after oocytes retrieval. The mean estrogen and progesterone levels on the EB day were 610.9 pg/ml (SEM = 78.44) and 45.4 ng/ml (SEM = 7.53), respectively. Histologic examination of the endometrium showed normal secretory endometrium consistent with day 16-17 of spontaneous ovulatory cycle. Two women who received combined contraceptive pills/gonadotropin therapy showed inactive endometrium with subnuclear vacuoles and decidual reaction in the stroma similar to that observed in women on estrogen-progestin birth control medication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587377 TI - Survey of 1120 Japanese women with a history of recurrent spontaneous abortions. AB - Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587378 TI - The effect of hormone replacement therapy on postmenopausal bone loss. AB - Eighty-four postmenopausal women who were randomly allocated to one of four groups, completed a 1 year follow-up. The first group (n = 20) received 0.625 mg/day conjugated estrogens cyclically (CE; 25 days/month). The second (n = 23) received 0.625 mg/day of CE continuously, and the third (n = 17) received 50 micrograms/day of transdermal 17 beta-estradiol cyclically (24 days/month). All these groups also received 2.5 mg of medroxiprogesterone acetate sequentially for the last 12 days of hormone replacement therapy, while the fourth group (n = 24) constituted a treatment-free control group. Dual photon absorptiometry was carried out before therapy and was repeated after 1 year. Serum calcium, phosphate and osteocalcine levels, and the urinary calcium/creatinine and hydroxyproline/creatinine ratios, were measured prior to treatment and 6 and 12 months thereafter. All treatment groups showed an increase in bone mineral content. This increase was higher in the continuous CE treatment group (4.4%, P less than 0.05) and in transdermal group (7.1%, P less than 0.01). Concomitant biochemical effects at 6 and 12 months, reduction in urine calcium and hydroxyproline, reduction in blood calcium, phosphate and osteocalcine, were compatible with the observed effects on bone mineral. PMID- 1587379 TI - Low-dose 17 beta-estradiol vaginal tablets in the treatment of atrophic vaginitis: a double-blind placebo controlled study. AB - The aim of the study was to investigate the effect of 25 micrograms 17 beta estradiol administered as a small vaginal tablet (Vagifem, Novo Nordisk A/S) on the symptoms of the vagina related to atrophy. The study was designed as a double blind randomized placebo controlled study running for 12 weeks. The women were treated once daily for 2 weeks with the active or the placebo tablet. During the subsequent 10 weeks the women were treated twice a week. One hundred and sixty four women were included. Ten dropped out for minor reasons, most of these due to lack of effect in the placebo group. In the Vagifem group 78.8% were suffering from moderate to severe atrophy of the vagina, compared with 81.9% in the placebo group. After 2 weeks the percentages were 14.3 and 35.3, respectively. After 12 weeks of treatment, 10.7% in the Vagifem group compared with 29.9% in the placebo group had moderate to severe atrophy (P less than 0.0001). A substantial part of the women complained about subjective symptoms such as vaginal dryness and dyspareunia. After 12 weeks of treatment, a significant improvement was found in the Vagifem group (P less than 0.002). Before treatment 53.1% in the treatment group and 41.0% in the placebo group were suffering from urological symptoms. After 2 weeks, 60.5% of the women in the Vagifem group underwent a change for the better compared to 35.3% in the placebo group. After 12 weeks of treatment the percentages in the two groups feeling an improvement were 62.8% and 32.4%. In this study local low-dose treatment with 25 micrograms 17 beta-estradiol was found to have a significant effect on the postmenopausal urogenital symptoms related to atrophy. PMID- 1587380 TI - Delta 5-3-beta-hydroxysteroid dehydrogenase activity in rat oviduct and implications of oviductal steroidogenesis. AB - Tubal factor in infertility is about one third. As part of an ongoing study of the mammalian oviduct the rat oviduct was serialised into 66 zones for the characterisation of 3 beta-hydroxysteroid dehydrogenase activity using substrates dehydroepiandosterone (DHA), pregnenolone and testosterone. Reactivity was quantified from 1-5 and was present in some of the preampullary zones of the rat oviduct in stromal and epithelial cells and completely absent in isthmic zones. Ultrastructural analysis of oviduct ampullaryisthmic zone 33 showed a probable epithelial steroidogenic cell with considerable amounts of smooth endoplasmic reticulum and hooded and circumnuclear mitochondria. The localisation of sterol dehydrogenase activity in some zones of the preampullary-ampullary segments in the rat oviduct opens up potentialities for the study of steroidogenesis in the mammalian oviduct. If the mammalian oviduct produces considerable amounts of steroids in some zones, as the histochemical activity demonstrates, then conditions such as luteinised unruptured follicle (LUF; with diagnostic peritoneal decrease in steroid concentration), steroid presence in oviductal fluid, ovulation control by the oviduct and even oocyte maturation and local steroid-peptide interactions are easily explainable. Without the zones model, it will not be possible to characterise the activity. PMID- 1587381 TI - Histology and fertility effects of polydioxanone on rat reproductive tissue. AB - This prospective study compares the histology and fertility effects of the microsuture polydioxanone to nylon and polyglactin-910. Twelve rats underwent uterine horn microroeanatomoses with nylon (6 right horns), polyglactin-910 (6 right horns), and polydioxanone (12 left horns). After mating, there were no significant differences in gestational implantations or adhesions per uterine horn. Postoperative histologic evaluation of nylon showed persistent histiocytic reaction and fibrosis, occasional giant cells, and suture persistence at 100 days. Polyglactin-910 had initial histiocytic responses, no giant cells or fibrosis, and was resorbed by 60 days. Polydioxanone had initial histiocytic reaction and giant cells, no fibrosis, and was resorbed by 100 days. Our findings, and a review of the literature, confirmed mixed histologic reactions but no difference in fertility with these three microsutures. Because of its low reactivity and great strength, polydioxanone may be a good alternative suture material in reproductive microsurgery. PMID- 1587382 TI - Simultaneous ectopic pregnancy with intra-uterine gestation after in vitro fertilization and embryo transfer. AB - A case of combined intra-uterine and tubal ectopic pregnancy is described following in vitro fertilization and the transfer of two four-cell and one two cell embryos. This phenomenon is known to be related to ovarian stimulation by gonadotropin therapy, and there is an increased risk with tubal disease. Techniques applied at the time of embryo transfer, the use of culture medium with 50% fetal cord serum to convey the embryos to the uterus, the catheterization method, and the position of the patient during transfer are presented. The risk of multiple pregnancies and combined intra-uterine and ectopic gestations increases with numbers of transfers and large volume of transfer medium. We would therefore recommend that after IVF-ET treatment in women with tubal disease, intensive care should be taken in the early follow-up period to rule out the possibility of ectopic pregnancy. In this case, a viable ongoing intra-uterine pregnancy was confirmed after surgery for right ampullary ectopic pregnancy. And a 2,925 g male in excellent condition was delivered by Cesarean section without complications. PMID- 1587383 TI - Subcapsular hemorrhage of the liver and hemoperitoneum in premature infants: report of 4 cases. AB - The occurrence of a subcapsular hemorrhage of the liver (SHL) with associated hemoperitoneum in four very low birth weight infants (VLBW) is described. We conclude from the analysis of these four cases and a review of the literature, that the pathogenesis of SHL is multifactorial, which emphasizes the extreme vulnerability of these infants. PMID- 1587384 TI - HPL-positive infiltrating trophoblastic cells in normal and abnormal pregnancy. AB - In a series of 24 pregnant women, placental bed biopsies were performed in the third trimester at cesarean section. All the resulting specimens contained infiltrating trophoblast with both small and giant cells, and eight also contained vascular trophoblast. On immunoperoxidase staining for HPL, some small interstitial trophoblastic cells were positive in 12 cases. Some cells of the vascular intramural trophoblast and practically all cells of the vascular intraluminal trophoblast were positive. Seven cases were normal pregnancies whereas 17 were complicated by arterial hypertension and/or fetal growth retardation. A significant correlation between abnormal pregnancy and absence of HPL-positive interstitial cells in the placental bed biopsy was found. This probably indicates a diminished overall number of HPL-positive interstitial cells in the group of abnormal pregnancies and might reflect some defect of interstitial trophoblast. Such a defect may play a role in the arrest of the physiological changes of pregnancy in spiral arteries, which has been described in pre-eclampsia and in many cases of idiopathic fetal growth retardation. PMID- 1587385 TI - Prolactin size variants during pregnancy in women with ovulatory hyperprolactinemia: characterization by isoelectric focusing and lectin affinity chromatography. AB - Previous studies from this laboratory have demonstrated the occurrence of important changes in PRL size heterogeneity in women with ovulatory hyperprolactinemia during gestation. A similar observation has been made, in normal women, for glycosylated PRL, which shows a progressive decrease as pregnancy progresses. In this study we decided to investigate the contribution of G-PRL on PRL heterogeneity throughout gestation in women with ovulatory hyperprolactinemia. Serum samples obtained throughout gestation were analysed by SDS-PAGE followed by immunoblotting and by isoelectric focusing of gels as well. The results indicated that, independent of the stage of pregnancy, the relative amounts of G-PRL as compared with the nonglycosylated form of the hormone remained quite constant. In addition, isoelectric focusing analyses of serum samples consistently resulted in an identical isoelectric point of PRL throughout all of the gestational period. These results suggested that changes in the relative proportions of PRL size species during pregnancy were not correlated with the degree of PRL glycosylation. Moreover, these observations further extended and supported the concept that the occurrence of PRL size heterogeneity depends mainly on thiol-disulfide interchange mechanisms, among PRL molecules, at the pituitary level. PMID- 1587386 TI - Cloning of a member of the arrestin family from a human thyroid cDNA library. AB - We used the cDNA of human retinal arrestin as a probe to screen a human thyroid cDNA library. We isolated and plaque-purified one clone (hTHY-ARRX). The nucleotide sequence of the 1.8 kb cDNA insert had an open reading frame of 1227 bp coding for a protein of 409 amino acids. Northern blot analysis revealed a single transcript of 1.7 kb in human thyroid cells. There is significant homology between amino acid sequences of human thyroid arrestin and human retinal arrestin (63%) and bovine beta-arrestin (74%), respectively. The hTHY-ARRX cDNA was stably transfected into Chinese hamster ovary cells already expressing a functional human thyrotropin (TSH) receptor. The cAMP response to TSH stimulation was unaltered in these cells, and homologous desensitization to TSH stimulation was not restored. It is not presently known whether hTHY-ARRX is human beta adrenergic arrestin or a new member of the arrestin family. PMID- 1587387 TI - FSH receptor mRNA is expressed stage-dependently during rat spermatogenesis. AB - In situ hybridization was performed on testicular tissue from adult male Sprague Dawley rats using cRNA antisense and sense probe of the monkey FSH receptor (FSHR) cDNA to determine the cellular site of synthesis, and possible stage dependent expression of FSHR mRNA during the cycle of the seminiferous epithelium. Using antisense probe specific binding was first detected in Sertoli cells just prior to sperm release at stage VIII. The strongest specific hybridization signal was found during stages IX and X followed by a decrease of signal intensity in stages XI-XII. No specific binding was found in stages XIII VII. The sequence of events with the maximum expression of FSHR mRNA in Sertoli cells in stages IX and X, before FSH-binding and FSH-stimulated cAMP production reach maximum values, coincides with a new wave of spermatogenesis and indicates an effect of FSH and spermatogenic cells on the regulation of FSHR mRNA expression. PMID- 1587388 TI - A point mutation of the T3 receptor beta 1 gene in a kindred of generalized resistance to thyroid hormone. AB - Mutations of the thyroid hormone receptor (TR) beta 1 gene have recently been detected in several unrelated families with generalized resistance to thyroid hormone (GRTH). We now report a novel point mutation in the TR beta 1 gene in a case of a Korean-Japanese kindred. The intracellular localization and the amount of TR proteins were considered to be normal by the immunocytochemical study of cultured skin fibroblasts from the patients using anti-T3 receptor antibody. The cDNA of the T3-binding domain of the TR beta 1 gene, synthesized from the total RNA of the patients' fibroblasts, was amplified by the polymerase chain reaction, and was sequenced. A point mutation, A to G, in one allele at 1612 resulting in an amino acid substitution from lysine 438 to glutamic acid was detected. The same mutation was identified in one allele in each of the affected members. In vitro translation products of the mutant TR beta 1 gene showed decreased T3 binding activity. These data suggest that a TR mutation is predominantly responsible for GRTH, irrespective of ethnic background. PMID- 1587389 TI - The Atlantic salmon prepro-gonadotropin releasing hormone gene and mRNA. AB - Screening for the gene encoding salmon gonadotropin releasing hormone (sGnRH) in an Atlantic salmon (Salmo salar) genomic library resulted in isolation of a positive clone designated lambda sGnRH-1. An anchor polymerase chain reaction (PCR) technique was used to amplify GnRH cDNA derived from salmon hypothalamic mRNA. The cDNA sequence was aligned to the 7607 base pair genomic sequence which was shown to encode the entire prepro-GnRH gene. The cDNA proved that the cloned gene is expressed in the hypothalamus of mature salmon. The coding domain of sGnRH differs from the mammalian GnRH by six nucleotide changes which allow the two amino acid differences between the two GnRH variants. Salmon GnRH associated peptide (GAP) differs extensively in sequence and size from the mammalian counterpart. Compared to the GnRH cDNA of a cichlid species the similarity is 69.3% in the protein coding sequence. PMID- 1587390 TI - Estrogenic regulation of heat shock protein 90 kDa in the rat ventromedial hypothalamus and uterus. AB - The regulation of heat shock protein 90 kDa (hsp90) by estradiol was analyzed in the rat ventromedial hypothalamus (VMH) and uterus by one-dimensional gel electrophoresis/Western blots. Protein from VMH and uterus (35 micrograms/sample) was resolved on 8% acrylamide gels, transferred to polyvinyldifluoride filters, and processed for immunoblotting using an anti-hsp90 antibody. Hsp90-specific bands were visualized on film using enhanced chemiluminescence and quantitated using a laser scanning densitometer. Hsp90 protein levels were significantly elevated in VMH at 12 h (p less than 0.01), and in uterus at 18 h (p less than 0.05) following estradiol injection (10 micrograms, s.c.). Immunocytochemical analysis for hsp90 localization by cell types showed that, in brain, hsp90 immunoreactivity was primarily neuronal. In the uterus, hsp90 immunoreactivity was most evident following treatment with estradiol, and was found primarily in the glandular epithelia; staining was less prominent in myometrium, stroma, and in the luminal epithelium. Thus, increased hsp90 levels may mediate some cellular responses to estrogen in specific cell types in both uterus and brain. PMID- 1587391 TI - Human endometrial adenocarcinoma cells express endothelin-1. AB - The expression of endothelin-1 (ET-1) in five human endometrial adenocarcinoma cell lines was studied. Using specific radioimmunoassay, immunoreactive ET-1 was detected in conditioned medium from two of the cell lines (RL 952 and HEC 1A). In reverse-phase high-performance liquid chromatography (HPLC), synthetic ET-1 and immunoreactive ET-1 from conditioned media revealed the same elution profile. By amplification of cDNA using the polymerase chain reaction, normal human endometrium as well as cell lines RL 952 and HEC 1A were shown to express ET-1 mRNA. In addition, cell line HEC 1B and KLE, which did not produce measurable amounts of immunoreactive ET-1, contained ET-1 specific mRNA whereas cell line AN3CA had no detectable ET-1 mRNA and did not secrete immunoreactive ET-1. PMID- 1587392 TI - Expression and function of a human thyroid hormone receptor-derived DNA-binding domain protein. AB - DNA binding domain proteins (DBDP) were prepared using a pET construct containing an insert coding for amino acids 49-122 of human thyroid hormone receptor (hTR) alpha and 103-179 of hTR beta. These proteins were expressed in Escherichia coli strain BL21 (DE3)-plysS after induction by isopropyl-D-thiogalactopyranoside (IPTG). The hTR alpha and hTR beta DBDP contain respectively 79 and 82 amino acids, including an amino terminal 4 amino acid extension derived from pET-3a or the synthesized initiation codon. Using a gel shift assay, both DBDPs were found to bind to a DNA oligonucleotide containing a thyroid hormone response element (TRE). The DBDPs competed with full length hTR alpha 1 for binding to the oligonucleotide. Apo-DBDPs (Zn2+ released by low pH) failed to bind to the palindromic TRE. DNA binding is restored however if apo-DBDP is preincubated in 500 microM Zn2+. When the DBDPs were expressed in COS-7 cells using a pCB6+ expression vector, they did not induce expression of a TRE-CAT fusion gene. hTR DBDPs thus can bind to DNA, presumably as monomers, since they do not contain the leucine zipper-like motif for dimerization. In COS-7 cells, they fail to cause transactivation of a TRE-CAT fusion gene. It is inferred that this may be because the DBDPs are not translocated to the nucleus or lack a transactivation domain. PMID- 1587393 TI - Why intraperitoneal delivery of insulin with implantable pumps in NIDDM? AB - In the normal state, pancreatic secretion of insulin results in a portal/peripheral gradient with the highest concentrations of insulin in the liver. In diabetic patients with absent or insufficient pancreatic insulin secretion who require exogenous insulin, this normal gradient is lost, resulting in numerous abnormalities. This consideration led to interest in the intraperitoneal delivery of insulin, hoping to produce a therapeutic state more closely resembling normal physiology. The development of implantable insulin pumps, which can deliver insulin intraperitoneally, led to numerous studies on insulin-dependent diabetes mellitus (IDDM) patients, demonstrating that insulin delivered intraperitoneally is rapidly and predictably absorbed with most of it going into the portal system, resulting in hepatic delivery of insulin. Studies in IDDM patients have demonstrated that good glucose control can be achieved with intraperitoneal delivery of insulin from implantable pumps with lesser glycemic fluctuations and, therefore, fewer episodes of hypoglycemia. Furthermore, intraperitoneal insulin results in carbohydrate and particularly lipid metabolism that more closely mimics the normal physiological state than produced by injections of insulin. Thus, implantable insulin pumps are being studied for use in IDDM. Many non-insulin-dependent diabetes mellitus (NIDDM) patients have insufficient pancreatic secretion and require exogenous insulin. Because of alterations in hepatic sensitivity to insulin, increments in insulin delivery to the liver may be even more important in NIDDM than IDDM. Furthermore, insulin resistance, which is an integral part of NIDDM, results in higher physiological levels of insulin, which are required for glucose control, and thus significant peripheral hyperinsulinemia occurs in patients receiving exogenous insulin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587394 TI - Attenuated glucose recovery from hypoglycemia in the elderly. AB - Advanced age is a risk factor for hypoglycemia caused by sulfonylureas (and insulin) used to treat diabetes mellitus. Therefore, we hypothesized that there is an age-associated impairment of glucose counterregulation and further that this is the result of a sedentary life-style. To test these hypotheses, glycemic and neuroendocrine responses to hypoglycemia, produced by 0.05 U/kg body wt insulin i.v. were measured in nondiabetic elderly subjects (age 65.1 +/- 0.9 yr n = 23)--and in a subset (n = 11) again after 1 yr of physical training (which increased VO2 max by 5.2 +/- 0.9 ml.kg-1.min-1, P less than 0.05)--and compared with these responses in nondiabetic young subjects (23.8 +/- 0.6 yr, n = 18). Recovery from hypoglycemia was attenuated (analysis of variance P less than 0.001) in the elderly (plasma glucose recovery rate 29.4 +/- 2.2 vs. 42.7 +/- 5.0 microM/min, P less than 0.02). This attenuation was the result of a smaller counterregulatory increment in glucose production (maximum increment 13.3 +/- 1.1 vs. 17.2 +/- 1.1 mumol.kg-1.min-1; P less than 0.05) rather than a greater increment in glucose utilization in the elderly. The attenuated glucose recovery was associated with higher plasma insulin concentrations (maximum increment 1385 +/- 122 vs. 940 +/- 72 pM, P less than 0.01) and reduced glucagon responses to hypoglycemia (maximum increment 43 +/- 6 vs. 66 +/- 12 ng/L). The epinephrine, norepinephrine, cortisol, and growth hormone responses were similar, although the epinephrine response was slightly delayed and the growth hormone response appeared smaller in the elderly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587395 TI - Cell and matrix components of the glomerular mesangium in type I diabetes. AB - In a cross-sectional study, glomerular basement membrane (GBM) width, the volume fractions of the mesangium (VvMes), its cell (VvCell) and matrix (VvMatx) components, and surface density of the peripheral capillary surface (SvPGBM) were measured in renal biopsies from 187 nondiabetic living related and cadaveric donors of kidneys for transplantation and from 150 patients with insulin dependent (type I) diabetes mellitus of 1-41 yr duration. In the diabetic patients, the matrix was the major factor in the expansion of the mesangium. However, both VvCell (0.11 +/- 0.04) and VvMatx (0.20 +/- 10) in diabetic patients exceeded the same measurements in nondiabetic subjects (0.07 +/- 0.02 for each component) (P less than 0.001 in each case). Linear regression analysis demonstrated significant correlations (P less than 0.001 for all) between GBM width, VvMes, VvCell, VvMatx, or SvPGBM and either urinary albumin excretion and creatinine clearance, with the higher correlation coefficients in all cases with albuminuria. Of the structural parameters, VvMatx correlated best with either functional measure by stepwise regression, with GBM as an added factor only with albuminuria. Therefore, although models of diabetic glomerulopathy must consider enlargement of both mesangial cells and matrix, the predominant factor in the progression of structural and functional renal disease is mesangial matrix expansion. PMID- 1587396 TI - Simultaneous insulinlike growth factor I and insulin resistance in obese Zucker rats. AB - It has recently been shown that the ability of insulinlike growth factor I (IGF I) to stimulate glucose uptake and to lower circulating amino acid levels is retained in insulin-resistant diabetic BB rats. To examine in vivo effects of IGF I in obese Zucker rats (another model of insulin resistance) 6 obese and 6 lean rats received euglycemic IGF-I infusions (0.65 nmol.kg-1.min-1). IGF-I-stimulated glucose uptake in obese rats was 50% lower than lean control rats (45.0 +/- 2.8 vs. 92.2 +/- 6.1 mumol.kg-1.min-1, respectively), even though the rise in circulating IGF-I levels was greater in the obese group during IGF-I infusion. In addition, branched chain amino acid concentrations that declined by 45% in lean controls were not suppressed significantly in obese rats (392 +/- 33 basal vs. 327 +/- 29 microM at 90 min). Equivalent results were observed during euglycemic insulin clamps (12 pmol.kg-1.min-1) in 7 obese and 11 lean rats. These studies demonstrate that obese Zucker rats are resistant to the effects of IGF-I and insulin on glucose and amino acid metabolism. PMID- 1587397 TI - Intracellular defects in glucose metabolism in obese patients with NIDDM. AB - Skeletal muscle insulin resistance in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) is characterized by decreased glucose uptake. Although reduced glycogen synthesis is thought to be the predominant cause for this deficit, studies supporting this notion often have been conducted at supraphysiological insulin concentrations in which glucose storage is the overwhelming pathway of glucose disposal. However, at lower, more physiological insulin concentrations, decreased muscle glucose oxidation could play a significant role. This study was undertaken to determine whether, under euglycemic conditions, insulin resistance for leg muscle glucose uptake in NIDDM patients is due primarily to decreased glucose storage or to oxidation. The leg balance technique and leg indirect calorimetry were used under steady-state euglycemic conditions to estimate muscle glucose uptake, storage, and oxidation in eight moderately obese NIDDM patients and eight matched-control subjects. Leg muscle biopsies also were performed to determine whether alterations in muscle pyruvate dehydrogenase or glycogen synthase activities could explain defects in glucose oxidation or storage. At insulin concentrations of approximately 500-600 pM, leg glucose uptake, oxidation, and storage in the NIDDM group (2.03 +/- 0.42, 1.00 +/- 0.13, 0.66 +/- 0.36 mumol.min-1.100 ml-1) were significantly lower (P less than 0.05) than rates in control subjects (5.14 +/- 0.64, 1.92 +/- 0.17, 2.80 +/- 0.54). Pyruvate dehydrogenase and glycogen synthase activities were also decreased, consistent with the in vivo metabolic defects. The average deficit in leg glucose uptake in NIDDM was 3.11 +/- 0.42 mumol.min-1.100 ml-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587398 TI - Prospective analysis of the insulin-resistance syndrome (syndrome X). AB - Many studies have shown that hyperinsulinemia and/or insulin resistance are related to various metabolic and physiological disorders including hypertension, dyslipidemia, and non-insulin-dependent diabetes mellitus. This syndrome has been termed Syndrome X. An important limitation of previous studies has been that they all have been cross sectional, and thus the presence of insulin resistance could be a consequence of the underlying metabolic disorders rather than its cause. We examined the relationship of fasting insulin concentration (as an indicator of insulin resistance) to the incidence of multiple metabolic abnormalities in the 8 yr follow-up of the cohort enrolled in the San Antonio Heart Study, a population based study of diabetes and cardiovascular disease in Mexican Americans and non Hispanic whites. In univariate analyses, fasting insulin was related to the incidence of the following conditions: hypertension, decreased high-density lipoprotein cholesterol concentration, increased triglyceride concentration, and non-insulin-dependent diabetes mellitus. Hyperinsulinemia was not related to increased low-density lipoprotein or total cholesterol concentration. In multivariate analyses, after adjustment for obesity and body fat distribution, fasting insulin continued to be significantly related to the incidence of decreased high-density lipoprotein cholesterol and increased triglyceride concentrations and to the incidence of non-insulin-dependent diabetes mellitus. Baseline insulin concentrations were higher in subjects who subsequently developed multiple metabolic disorders. These results were not attributable to differences in baseline obesity and were similar in Mexican Americans and non Hispanic whites. These results support the existence of a metabolic syndrome and the relationship of that syndrome to multiple metabolic disorders by showing that elevations of insulin concentration precede the development of numerous metabolic disorders. PMID- 1587399 TI - Role of glucose transporters in glucocorticoid-induced insulin resistance. GLUT4 isoform in rat skeletal muscle is not decreased by dexamethasone. AB - The diabetogenic effects of glucocorticoid excess are due in part to peripheral resistance to insulin. To test the hypothesis that glucocorticoid-induced peripheral insulin resistance might be attributable to a decreased number of glucose transporters, we examined the effects of dexamethasone treatment on the expression of the GLUT4 (insulin regulatable) glucose transporter in skeletal muscle, the major site of insulin-mediated glucose uptake. Dexamethasone treatment of rats (1 mg/day for 1 wk) induced hyperglycemia and hyperinsulinemia. At dosages of either 0.1 or 1 mg/day, insulin-stimulated 2-deoxyglucose uptake in isolated soleus muscle was reduced by greater than or equal to 50%, demonstrating the presence of insulin resistance in skeletal muscle. Immunoblots of crude membranes from deep quadriceps muscle showed that dexamethasone treatment (1 mg/day) increased the amount of GLUT4 protein by 84%. GLUT4 mRNA abundance was similarly increased when expressed per unit RNA but was unchanged when expressed on a DNA basis because the tissue RNA content was decreased by dexamethasone. In contrast to quadriceps, GLUT4 protein concentration in soleus and extensor digitorum longus extracts was not significantly increased by dexamethasone treatment. Because glucocorticoids cause selective atrophy of type IIb muscle fibers, which express relatively less GLUT4 protein, the apparent increase in GLUT4 content in quadriceps muscle from dexamethasone-treated animals may have resulted from inadvertent increased sampling of GLUT4-enriched type I and IIA fibers, caused by a glucocorticoid-induced decrease in the relative mass of the GLUT4-poor type IIb fibers. We conclude that glucocorticoids do not decrease GLUT4 content in skeletal muscle and that glucocorticoid-induced insulin resistance in this tissue is not due to suppression of glucose transporter gene expression. PMID- 1587400 TI - Prospective study of microalbuminuria as predictor of mortality in NIDDM. AB - Retrospective studies of patients with non-insulin-dependent diabetes mellitus (NIDDM) have suggested that microalbuminuria predicts early all-cause (mainly cardiovascular) mortality independently of arterial blood pressure. These findings have not been confirmed in prospective studies, and it is not known whether the predictive power of microalbuminuria is independent of other major cardiovascular risk factors. During 1985-1987, we examined a representative group of 141 nonproteinuric patients with NIDDM for the prevalence of coronary heart disease and several of its established and putative risk factors, including raised urinary albumin excretion (UAE) rate. Thirty-six patients had microalbuminuria (UAE 20-200 micrograms/min), and 105 had normal UAE (less than 20 micrograms/min). At follow-up, an average of 3.4 yr later, 14 patients had died. There was a highly significant excess mortality (chiefly from cardiovascular disease) among those with microalbuminuria (28%) compared to those without microalbuminuria (4%, P less than 0.001). In univariate survival analysis, significant predictors of all-cause mortality included microalbuminuria (P less than 0.001), hypercholesterolemia (P less than 0.01), hypertriglyceridemia (P less than 0.05), and preexisting coronary heart disease (P less than 0.05). The predictive power of microalbuminuria persisted after adjustment for the effects of other major risk factors (P less than 0.05). We conclude that microalbuminuria is a significant risk marker for mortality in NIDDM, independent of the other risk factors examined. Its presence can be regarded as an index of increased cardiovascular vulnerability and a signal for vigorous efforts at correction of known risk factors. PMID- 1587401 TI - Diurnal variation in glucose tolerance. Cyclic suppression of insulin action and insulin secretion in normal-weight, but not obese, subjects. AB - The relative roles of insulin sensitivity, insulin secretion, and glucose effectiveness to the diurnal rhythm of glucose tolerance were examined in normal weight (n = 12) and obese (n = 11) subjects. Two frequently sampled intravenous glucose tolerance tests were performed in each subject at 0800 on one occasion and 1800 on a separate day. Tests were preceded by identical fasts of 10-12 h. In nonobese subjects, glucose tolerance, expressed as the 10- to 16-min KG value (KGs), was much reduced in the evening (AM 2.98 +/- 0.45, PM 1.86 +/- 0.33 min-1, P less than 0.002). In the obese subjects, tolerance was lower in the morning than normal-weight subjects (2.19 +/- 0.31 min-1), but unlike in nonobese subjects, tolerance was not significantly reduced during the day (1.90 +/- 0.18 min-1, P greater than 0.40). The reduction in glucose tolerance in the normal weight subjects was caused by diminished insulin sensitivity (parameter S1, AM 15.4 +/- 2.9, PM 10.2 +/- 1.9 x 10(-5) min-1/pM, P less than 0.01) and reduced beta-cell responsivity to glucose. The evening decrease in the latter was reflected both in first-phase plasma insulin (AM 2466 +/- 441, PM 1825 +/- 381 pM/10 min, P less than 0.05) and the potentiation slope (AM 462 +/- 68, PM 267 +/ 35 pM/mM, P less than 0.01). In contrast, consistent with no diurnal variation in glucose tolerance, obese subjects exhibited no decline in insulin sensitivity in the evening (AM 3.6 +/- 0.7, PM 4.9 +/- 1.0 x 10(-5) min-1/pM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587402 TI - Abnormal myoinositol influx in human leucocytes in diabetes but not specifically in diabetic neuropathy. AB - Abnormal myoinositol metabolism has been implicated as a contributor to the development of diabetic neuropathy. Furthermore, in vitro glucose inhibits animal and human myoinositol transporters. To investigate whether myoinositol transport is abnormal in diabetic subjects with and without neuropathy, we used a triple isotope technique to measure [14C]myoinositol uptake in leucocytes from 23 insulin-dependent diabetic subjects and 13 matched nondiabetic subjects. All subjects with diabetes underwent neurophysiological studies, and subjects without neuropathy were compared with those with various degrees of neuropathy. The relationship between glycemia and flux was also studied. Diabetic subjects had similar intracellular and plasma myoinositol concentrations but had higher rates of uptake of myoinositol over the extracellular concentrations of myoinositol studied. Although the derived Km, Vmax, and passive components were not significantly different, the Vmax:Km ratio was significantly higher in diabetic subjects compared with nondiabetic subjects (0.25 [0.17-0.32] vs. 0.16 [0.13 0.19], respectively (P = 0.006). In diabetic subjects, the rate of myoinositol uptake correlated with HbA1c, particularly at 3 microM extracellular myoinositol where active uptake was a high proportion of the total influx (P less than 0.005). No difference in myoinositol uptake was found among diabetic subjects with various degrees of neuropathy. We conclude that although myoinositol transport is abnormal in diabetes, it is not specifically abnormal in diabetic neuropathy. Prolonged hyperglycemia is associated with higher myoinositol flux. PMID- 1587403 TI - Dual and asynchronous deposition of laminin chains at the epithelial-mesenchymal interface in the gut. AB - The production of laminin by 14-day fetal rat intestinal endoderm and mesenchyme was investigated. The amount of neosynthesized laminin was measured after purification using affinity chromatography. Chain composition of laminin was analyzed by immunoblotting and immunofluorescence staining. The data show that both embryonic intestinal tissue components synthesize laminin and that A and B1/B2 chains were detected in both endodermal and mesenchymal cells. The cellular source of laminin found at the epithelial basement membrane has been studied by immunocytochemistry in rat/chick or mouse/chick interspecies hybrid intestines taken at various stages of development. Immunodetection of the whole laminin molecule and of the individual A and B1/B2 chains by rodent-specific polyclonal and monoclonal antibodies at the basement membrane level in these hybrid intestines revealed (a) laminin molecules, which originate from both mesenchymal and endodermal cells; (b) deposition of A and B1/B2 chains by endodermal cells, regardless of the stage of growth of the hybrid intestines; and (c) asynchronous deposition of the various chains of laminin into the basement membrane by the mesenchyme. B1/B2 chains are deposited concomitant with contact with the epithelium, whereas A chains appear only later (13 days after grafting). These data reinforce the suggestion from previous studies that cooperation between epithelium and mesenchyme is necessary for the formation of a complete basement membrane in the developing intestine. PMID- 1587404 TI - Mucosal ouabain and Na+ inhibit active Rb+(K+) absorption in normal and sodium depleted rat distal colon. AB - To determine the effect of mucosal sodium and mucosal ouabain on active Rb+(K+) absorption, unidirectional and net 86Rb+ fluxes were measured under voltage-clamp conditions in the distal colon of normal and sodium-depleted rats. The role of mucosal sodium (independent of serosal sodium) was evaluated in a model of Rb+(K+) absorption in which serosal ouabain markedly enhanced active Rb+(K+) absorption. In normal rats, mucosal sodium was a competitive inhibitor of Rb+(K+) absorption, and Rb+(K+) absorption consisted of a mucosal sodium-sensitive component and a mucosal sodium-insensitive component. Further, mucosal ouabain almost completely inhibited the mucosal sodium-insensitive component but did not affect the mucosal sodium-sensitive component. In sodium-depleted rats, both mucosal sodium-sensitive and mucosal sodium-insensitive fractions of Rb+(K+) absorption were also identified. Aldosterone markedly stimulated the mucosal sodium-sensitive component (1.68 +/- 0.15 vs. 0.60 +/- 0.10 muEq.h-1.cm-2) but not the sodium-insensitive component (0.88 +/- 0.09 vs. 0.64 +/- 0.06 muEq.h-1.cm 2) component of Rb+(K+) absorption; however, in contrast to normal animals, mucosal sodium in sodium-depleted animals was a noncompetitive inhibitor of Rb+(K+) absorption. The mucosal sodium-insensitive component of Rb+(K+) absorption in sodium-depleted animals was substantially inhibited by mucosal ouabain, but the mucosal sodium-sensitive component, unlike that in normal animals, was partially inhibited by mucosal ouabain. These studies indicate that the characteristics of the Rb+(K+) absorptive process in sodium-depleted animals differ significantly from those present in normal animals, suggesting that aldosterone induces an Rb+(K+) absorptive mechanism not present in normal animals. PMID- 1587405 TI - Electrical acustimulation relieves vection-induced motion sickness. AB - The aim of this study was to examine the effects of electrical acustimulation on gastric myoelectric activity and severity of symptoms of motion sickness. In experiment 1, 16 Chinese subjects received electrical acustimulation in one of two sessions. In experiment 2, 45 white and black American subjects were randomly divided into three groups: acustimulation, sham acustimulation, and control. Each subject sat in an optokinetic drum for 15 minutes baseline and 15 minutes of drum rotation. Subjects' electrogastrograms and subjective symptoms of motion sickness were obtained. In experiment 1, the mean symptom score and tachyarrhythmia during acustimulation sessions were significantly lower than during no-acustimulation sessions. In experiment 2, the mean symptom score of the acustimulation group was significantly lower than that of the sham-stimulation group and the control group; tachyarrhythmia in the acustimulation group was significantly less than that of the control group but not the sham-stimulation group. In conclusion, electrical acustimulation reduces the severity of symptoms of motion sickness and appears to decrease gastric tachyarrhythmia. PMID- 1587406 TI - Primary sclerosing cholangitis in ulcerative colitis--a risk factor for the development of dysplasia and DNA aneuploidy? AB - In a 15-year surveillance program for long-standing, total ulcerative colitis (UC), 72 patients were followed up with colonoscopic biopsies. Seventeen patients developed definite dysplasia, carcinoma, and/or DNA aneuploidy. Alkaline phosphatase and transaminases were examined in all patients. In the group with dysplasia, carcinoma, and/or DNA aneuploidy, 5 patients (28%) were found to have primary sclerosing cholangitis (PSC) based on histological and/or cholangiographic criteria. In the group without definite dysplasia or DNA aneuploidy, no patient with PSC appeared, although two patients with other forms of chronic liver disorders were found. The difference in distribution of PSC between the two groups was statistically significant (P = 0.0004). Using logistic regression, the presence of PSC and the duration of UC were identified as independent risk factors associated with dysplasia and/or DNA aneuploidy. Thus, UC patients with PSC seem to run an increased risk of developing colonic dysplasia and/or DNA aneuploidy. Although the reason for the increased risk is still unclear, these results warrant increased surveillance among patients with both PSC and longstanding, total UC. PMID- 1587407 TI - Mechanism of gastric mucosal damage induced by ammonia. AB - The mechanism for Helicobacter pylori-induced gastric mucosal injury remains obscure. H. pylori has high urease activity to produce ammonia from urea in the stomach. In this study, the effects of ammonia on (a) gastric mucosal integrity, (b) gastric mucosal hemodynamics, (c) mucosal cellular viability, (d) mitochondrial respiration, and (e) energy metabolism of gastric mucosal were investigated. Ammonia (pH 10.3) at concentrations of greater than 125 mmol/L caused acute macroscopic gastric mucosal lesions in a dose-dependent manner, whereas glycine-NaOH buffer (pH 10.3) or ammonium chloride (pH 4.5) did not. The decrease in energy charge preceded the occurrence of gastric mucosal lesions, but ammonia caused no change in mucosal hemodynamics. Oxygen consumption of isolated cells and mitochondria of gastric mucosa was inhibited by ammonia dose dependently. The present results indicate that ammonia impairs mitochondrial and cellular respiration and energy metabolism and that ammonia decreases mucosal cell viability, leading subsequently to mucosal damage. PMID- 1587408 TI - Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome. AB - Colonic motor activity and plasma concentrations of cholecystokinin (CCK) both increase after oral intake of a meal. Thus, CCK had been thought to mediate the postprandial increase in colonic motor activity, which is termed gastrocolonic response. The present study used the substance loxiglumide, which acts as a specific antagonist at the CCK-A receptor, to evaluate this hypothesis. In the first set of experiments, eight healthy subjects were studied four times on separate days. A multilumen catheter was endoscopically placed with its tip lying in the descending colon. Motor activity was recorded by a low-compliance perfusion manometry system at six locations 60-45 cm from the anus. Basal activity was recorded for at least 2 hours to achieve steady-state conditions. The order of the following four experiments was randomized: (a) intravenous infusion of the CCK analogue cerulein at increasing doses (7.5, 15, 30, and 60 ng/kg.h, each given for 30 minutes); (b) intravenous cerulein plus 5 mg/kg.h loxiglumide; (c) a 1000-kcal solid/liquid meal consisting of regular German food; and (d) a meal plus 5 mg/kg.h loxiglumide. In the second set of experiments, eight patients with irritable bowel syndrome were studied twice on two separate days, and two experiments were performed n randomized order: (a) a 1000-kcal solid/liquid meal consisting of regular German food; or (b) a meal plus 5 mg/kg.h loxiglumide. The motor index was calculated as the area under contractions by a computerized system. The 1000-kcal meal markedly increased colonic motor activity. This gastrocolonic response was significantly greater in patients with irritable bowel syndrome than in healthy volunteers. Cerulein stimulated motor activity only at pharmacological doses (30-60 ng/kg.h), which resulted in plasma CCK levels markedly exceeding postprandial values. Loxiglumide abolished the effects of cerulein even at pharmacological doses. However, loxiglumide did not inhibit the gastrocolonic response to a regular meal either in healthy volunteers or in patients with irritable bowel syndrome. Loxiglumide also failed to alter the interdigestive colonic motor activity. Therefore, effects mediated by the CCK A receptor do not play a major physiological role in the regulation of the interdigestive and postprandial motility of the left colon. PMID- 1587409 TI - Long-term nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori. AB - To evaluate the association of Helicobacter pylori infection with gastroduodenal ulceration and symptoms in rheumatoid arthritis patients chronically ingesting nonsteroidal anti-inflammatory drugs (NSAIDs), a population-based study was performed. Residents of Olmsted County, Minnesota, and surrounding counties, 40 years of age and over with active rheumatoid arthritis taking therapeutic dose of NSAIDs daily for 6 months or more were evaluated (n = 50). An endoscopic score from 0 to 5 was assigned and independently confirmed. Biopsies were obtained from the antrum and gastric body for the presence of H. pylori. A symptom score based on the frequency and severity of dyspeptic symptoms was calculated. Substantial mucosal injury (greater than or equal to grade 2) was observed at endoscopy in 33 patients (66%); 14 (28%) had chronic ulcers. Eleven of the community patients with rheumatoid arthritis (22%) were H. pylori positive; adjusting for age, the prevalence of H. pylori was not significantly different to that in 67 health controls (25%). One or more upper gastrointestinal symptoms were reported by 19 of the community patients (38%). Adjusting for age, community rheumatoid arthritis patients with H. pylori were not more likely to have visible mucosal damage or dyspepsia, but were significantly more likely to have histological gastritis (P less than 0.01). The results suggest that, in primarily asymptomatic persons from the community with rheumatoid arthritis taking daily NSAIDs for 6 months or more, H. pylori infection is not related to the severity of visible mucosal injury. PMID- 1587410 TI - Increased collagen type III synthesis by fibroblasts isolated from strictures of patients with Crohn's disease. AB - Increased type III collagen deposition in all layers of the intestinal tract, including the lamina propria, is a common feature of strictures in Crohn's disease. In the present study, it was found that in comparison with fibroblasts from normal or nonstrictured but inflamed intestinal lamina propria, the fibroblasts isolated from strictures of patients with Crohn's disease produce significantly more collagen, especially collagen type III. Transforming growth factor beta 1 (TGF-beta 1) significantly increased collagen type III synthesis in intestinal lamina propria fibroblasts isolated from all patients. The effect of TGF-beta 1 on type III collagen synthesis in fibroblasts from strictures in Crohn's disease was significantly higher than that in fibroblasts from inflamed specimens of the same patients. In contrast, platelet-derived growth factor decreased collagen type III synthesis in lamina propria fibroblasts derived from strictures compared with fibroblasts from nonstrictured but inflamed tissue. These findings indicate that fibroblasts in the lamina propria of patients with Crohn's disease have a different reactivity towards cytokines. On the basis of increased type III collagen deposition in intestinal strictures of Crohn's disease by using cell adhesion and cell proliferation assays, it was shown that collagen type III stimulated adhesion and proliferation of lamina propria fibroblasts. The current data provide evidence that the different reactivity of mesenchymal cells to cytokines in terms of synthesizing type III collagen fibrils, which is a major component of collagen fibrils, may play an important role in the pathogenesis of fibrosis and stricture formation in chronic inflammatory bowel diseases. PMID- 1587411 TI - Development of gap junctions between gastric surface mucous cells during cell maturation in rats. AB - The development of gap junctions in rat gastric surface mucous cells during their maturation were examined by indirect immunofluorescence and freeze-fracture methods. Monoclonal antibody against liver gap junction protein stained in large spots along the intercellular junctions between mature gastric surface mucous cells. On the other hand, relatively small fluorescent spots were present over the immature surface mucous cells. The freeze-fracture method showed many large irregular gap junctions between mature surface mucous cells. In immature surface mucous cells, the gap junctions were less developed than those of mature cells, and small gap junctions were occasionally associated with tight junctional strands. Quantitatively, the gap junctions in mature cells were larger and more numerous than those in immature cells. These findings show that gap junctions develop during the maturation of surface mucous cells and suggest that the intercellular communication mediated by gap junctions between gastric surface mucous cells plays an important role in the regulation of cell differentiation and in tissue homeostasis. PMID- 1587412 TI - The effect of diarrhea on fecal fat excretion. AB - To determine whether diarrhea increases fecal fat excretion, fecal fat output was measured during three consecutive days in normal subjects and in normal subjects in whom diarrhea was purposefully induced. Mean fecal fat output in normal subjects was 3.4 g/day; the upper limit of normal was 6.4 g/day. Twenty-one percent of subjects with mild to moderate diarrhea (fecal weight 200-800 g/day) and 58% of subjects with severe diarrhea (fecal weight greater than 800 g/day) had fecal fat excretion above the upper limit of normal, with values as high as 13.6 g/day. It is concluded that (a) diarrhea itself can induce mild secondary steatorrhea, and (b) when the quantitative fecal fat test is used in patients with diarrhea, mild abnormalities (up to 14 g/day) are not specific for a primary defect in fat digestion or absorption, i.e., they may represent false-positive results. PMID- 1587413 TI - Crohn's disease among ethnic groups in a large health maintenance organization. AB - The epidemiology of Crohn's disease (CD) was investigated among ethnic groups in a 2-million-member health maintenance organization. Between 1982 and 1988 there were 909 hospitalizations for CD. Annual hospitalizations per 100,000 were much lower for Hispanics (0.6) than those for whites (10.2) and blacks (10.2), and rates were higher among women (8.3) than men (6.0) (P less than 0.001). Bimodal age distributions were found for both sexes with peaks identified in the 20-29 year and greater than or equal to 60-year age groups. Annual age-adjusted hospitalizations per 100,000 decreased from 1982 (8.3) through 1988 (5.4) (P less than 0.05). A mail survey and medical records were used to collect data from the 169 CD patients who were identified at two sites within the organization. Prevalence rates per 100,000 for Hispanics (4.1) and Asians (5.6) were much lower than those for whites (43.6), blacks (29.8), and "others" (8.4). The distribution of age at diagnosis was bimodal, and the average age at diagnosis was 36 years. Patients reported an average of 3.7 outpatient visits and 13.3 days lost from work per year. Current cigarette smokers reported significantly more days troubled by symptoms during a one-month period (15.4 days) than nonsmokers (5.0 days) (P less than 0.001). PMID- 1587414 TI - Corticosteroid treatment for inflammatory bowel disease in pediatric patients increases intraocular pressure. AB - Intraocular pressure (IOP) was measured in 54 pediatric patients (aged 7-21 years) with inflammatory bowel disease (IBD) who were treated with oral prednisone for 1-104 months. The difference in mean IOP between the treated patients (mean +/- SD, 15.62 +/- 4.11 mm Hg) and 55 age-matched controls (13.83 +/- 2.42 mm Hg) was statistically significant (P = 0.007). The IBD patients were classified as group I, IOP less than or equal to 19 mm Hg in both eyes, and group II, IOP greater than or equal to 20 mm Hg in either eye. Twelve of the 54 patients (22.2%) and none of the controls had IOP greater than or equal to 20 mm Hg (P less than 0.001). Seventeen of the 54 patients (31.5%) were characterized as "steroid responders" (IOP of greater than or equal to 20 mm Hg, change in IOP of greater than or equal to 6 mm Hg between visits, or difference in IOP of greater than or equal to 6 mm Hg between the two eyes). When the dose of prednisone was reduced to 0-10 mg/day 30 days or more before measurement, 9 steroid responders showed a decrease in IOP to within 2 SD of the mean control IOP; 7 of the 9 showed a decrease in IOP of greater than or equal to 6 mm Hg. These observations indicate that while prednisone is a causative factor in increasing the IOP, susceptibility to average doses of prednisone is highly variable, and patients need to be monitored on an individual basis. Because IBD is a chronic disorder that requires prolonged corticosteroid treatment, these children are at risk of developing steroid-induced glaucoma. Careful ophthalmologic monitoring of pediatric IBD patients, as well as of other pediatric patients who receive corticosteroid therapy, is recommended. PMID- 1587415 TI - Symptoms of irritable bowel syndrome in a British urban community: consulters and nonconsulters. AB - Because the prevalence of the irritable bowel syndrome (IBS) in the general population is unknown, a questionnaire of intestinal symptoms was administered to a stratified random sample of 1058 women and 838 men. Subjects were asked if they had consulted a physician about such symptoms. One or more symptoms occurred frequently in 47% of women and 27% of men. Diagnosable IBS, defined as three or more symptoms, was present in 13% of women and 5% of men. Abdominal pain was the most common symptom, and recurrent intestinal pain was reported by 20% of women and 10% of men. All symptoms were more common in women except runny or watery stools. Most symptoms including pain were unrelated to age. Only half the people with diagnosable IBS had consulted a physician about it. The likelihood of consulting a physician was directly proportional to the number of symptoms and was similar in men and women after controlling for the number of symptoms. Of individual symptoms, the one most strongly associated with consulting was abdominal pain, especially in men. It is concluded that IBS is prevalent at all ages, especially in women, that it is nearly always painful, and that people with multiple symptoms are more likely to consult a physician. PMID- 1587416 TI - Mesenteric vasoconstriction in cardiogenic shock in pigs. AB - The quantitative impact of mesenteric vasoconstriction on the systemic hemodynamic response to cardiogenic shock induced by pericardial tamponade was evaluated. Graded increases in pericardial pressure produced corresponding decreases in cardiac output to 44% +/- 2% and arterial pressure to 64% +/- 3% of baseline and increases in total peripheral vascular resistance to 131% +/- 4% of baseline. Total mesenteric blood flow decreased disproportionately, to 28% +/- 3% of baseline, because of a disproportionate increase in mesenteric vascular resistance to 223% +/- 6% of baseline. Nonmesenteric vascular resistance increased only to 119% +/- 4% of baseline. Thus mesenteric vasoconstriction accounted for 42% of the increase in total peripheral resistance. Prior blockade of the renin-angiotensin axis ablated this response and eliminated the mesenteric contribution to systemic vascular resistance, while confirmed blockade of the alpha-adrenergic system or vasopressin system had no effect. Without shock, central intravenous infusions of angiotensin II (but not norepinephrine or vasopressin) closely mimicked this selective vasoconstriction. Angiotensin mediated selective mesenteric vasoconstriction accounts for more than 40% of the overall increase in systemic vascular resistance in cardiogenic shock. PMID- 1587417 TI - Jejunal toxin inactivation regulates susceptibility of the immature rat to STa. AB - The immature rat jejunum demonstrates an increased response, sensitivity, and susceptibility to heat-stable enterotoxin. In the present study, the hypothesis that this increased secretory response results from diminished jejunal toxin inactivation and persistence of biologically active toxin was tested. A modification of toxin injected into ligated jejunal loops was observed in both adult and immature rats. However, in the immature jejunum there was also persistence of biologically active toxin and continued toxin-induced secretion. In contrast, in the adult jejunum there was inactivation of toxin and cessation of secretion. Incubation of toxin with luminal fluid, pancreatic fluid, or jejunal brush border membranes resulted in toxin alteration. However, a completely inactive toxin species was generated only after incubation with jejunal organ culture slices. It is concluded that (a) incomplete toxin inactivation in the immature rat jejunum contributes to prolonged intestinal secretion and that (b) the inactivation process is multifactorial, but it is likely that final toxin inactivation requires the participation of the enterocyte. These findings may help explain the increased responsiveness of the immature intestine to heat-stable enterotoxin. PMID- 1587418 TI - High-affinity binding is essential for enhancement of intestinal Fe2+ and Ca2+ uptake by bile salts. AB - Both calcium and iron are bound with high affinity by premicellar bile salts having cholanic ring 7-OH and/or 12-OH groups, forming soluble cation-bile salt complexes. The authors of the current study recently showed that premicellar taurocholate markedly enhances intestinal iron and calcium uptake. However, the relationship of high-affinity binding to the observed uptake enhancement was unknown. In the current study, this relationship was examined by studying taurodehydrocholate (TDHC) binding and intestinal uptake of both cations. Ca2+ binding was measured by noting depression of [Ca2+] activity in solutions containing constant total Ca concentrations (1 mmol/L) and varying [TDHC] (0.5-50 mmol/L). Fe2+ binding was assessed by equilibrium dialysis studies of 59FeSO4 (0.179-1.79 mmol/L) and TDHC (0.5-50 mmol/L). Effects of TDHC on intestinal Fe2+ and Ca2+ uptake were measured in isolated perfused intestinal segments in vivo in seven and eight Sprague-Dawley rats, respectively. TDHC, lacking ring OH groups, did not bind either cation with high affinity and had no effect on their intestinal uptake. These results suggest that high-affinity binding is essential for bile salt-induced enhancement of intestinal Fe2+ and Ca2+ uptake. PMID- 1587419 TI - Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease. AB - Serum levels of soluble interleukin 2 receptor (sIL-2R) have been proposed as a clinical marker of inflammatory bowel disease. The source of sIL-2R in patients with Crohn's disease and ulcerative colitis is unknown, and other soluble receptors have not been investigated. In the present study, sIL-2R and soluble CD8 and CD4 levels were measured in plasma and culture supernatants of peripheral blood and intestinal mucosal mononuclear cells from patients with inflammatory bowel disease, surgical controls, and healthy subjects. Level of plasma sIL-2R was significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy volunteers. Intestinal cells always produced more sIL-2R than peripheral cells. Spontaneous sIL-2R production by mucosal cells was significantly elevated in Crohn's disease but not in ulcerative colitis supernatants compared with levels of surgical controls. Soluble CD8 and CD4 were poor indicators of systemic or mucosal immunity. A positive correlation was found between plasma sIL-2R and spontaneous production by intestinal cells of patients with Crohn's disease and surgical control patients, whereas ulcerative colitis plasma sIL-2R correlated with spontaneous production by peripheral cells. The association of plasma or spontaneous sIL-2R levels with the degree of intestinal inflammation was weak, and there was a wide overlap with control values. Therefore, caution should be used before considering sIL-2R an accurate marker of inflammatory bowel disease activity. PMID- 1587420 TI - Monensin action on the Golgi complex in perfused rat liver: evidence against bile salt vesicular transport. AB - Several studies suggest that bile salts are transported from the basolateral to the canalicular membrane of hepatocytes by a vesicular pathway, possibly in part via the Golgi complex. To test this hypothesis, the present study examined, in the perfused rat liver, the influence of the Na+ ionophore monensin on the biliary secretion of taurocholate and biliary lipids. The effects of the drug have been checked by the study of the ultrastructural modifications of the Golgi complex, secretion of horseradish peroxidase, and bile salt uptake. An infusion of monensin (1, 3, or 5 mumol/L) into the liver induced considerable swelling of the Golgi complex within 5 minutes. After a bolus injection of horseradish peroxidase during monensin infusion, the biliary secretion of the protein was delayed (1 mumol/L monensin) and markedly reduced (5 mumol/L monensin). Bile salt uptake was virtually unchanged except with 5 mumol/L monensin. This suggests that monensin has the same effects on the subcellular traffic in the perfused liver as in cultured cells. After a bolus injection of taurocholate (0.25, 5.0, or 8.5 mumol/100 g body wt) during monensin infusion, the pattern of biliary secretion of the bile salt was identical to that of controls. During continuous infusion of taurocholate, a 10-minute monensin infusion (1 or 3 mumol/L) had no effect on the biliary secretion of taurocholate and on the secretion of lecithin and cholesterol induced by taurocholate. High concentrations (5 mumol/L) or prolonged infusions (20 minutes) of monensin decreased the biliary secretion of bile salts but corresponded to a marked decrease of taurocholate uptake. In summary, the Na+ ionophore monensin altered the Golgi complex and the vesicular transport of horseradish peroxidase, whereas taurocholate biliary secretion was not influenced unless taurocholate biliary secretion was not influenced unless taurocholate uptake by the liver was markedly decreased. It may be concluded that taurocholate and biliary lipid secretion, under these conditions, does not depend essentially on pathways involving acidic transporting vesicles and particularly the trans Golgi complex. PMID- 1587421 TI - Mechanism of insulin resistance associated with liver cirrhosis. AB - Insulin-induced glucose metabolism was investigated in 26 patients with biopsy proven liver cirrhosis and 10 control subjects. Two glucose clamp protocols together with continuous indirect calorimetry were performed to examine whether reduced rates of glucose oxidation and/or nonoxidative glucose metabolism explain insulin resistance in liver cirrhosis. Using a 4-hour, two-step protocol (0-2 hours, plasma glucose 5.2 mmol/L, plasma insulin 92 mU/L to test the half-maximum response; 2-4 hours, hyperglycemia 10.0 mmol/L, plasma insulin 442 mU/L to test the maximum cellular glucose disposal) liver cirrhosis reduced glucose disposal to 45% and 60% of control values, respectively. Simultaneously, insulin-induced increases in glucose oxidation, plasma lactate levels, and lipogenesis were normal, whereas nonoxidative glucose metabolism was reduced (-82% and -47% of controls, respectively). To determine whether reduced nonoxidative glucose metabolism was caused by reduced glucose disposal, glucose disposal was "matched" to normal values in a subgroup of cirrhotic patients. Nonoxidative glucose metabolism values were normal, but plasma lactate concentrations disproportionally increased (+96%) after "matching" glucose disposal. Insulin resistance was independent of the etiology of the cirrhosis, the biochemical parameters of parenchymal cell damage and liver function, and the clinical and nutritional state of the patients. It is concluded that liver cirrhosis impairs insulin sensitivity and maximum cellular glucose disposal. Reduced glucose disposal is caused by defective glucose storage. Insulin resistance is independent of the etiology of liver cirrhosis and of the clinical and nutritional state of the patient. PMID- 1587422 TI - Lithotripsy plus ursodiol is superior to ursodiol alone for cholesterol gallstones. AB - The safety and efficacy of gallbladder extracorporeal shock-wave lithotripsy combined with 600 mg/day ursodiol were examined in 85 patients with radiolucent gallstones, 15 with lightly calcified gallstones, and 12 with radiolucent stones pretreated for greater than or equal to 2 months with 600 mg/day ursodiol. Results were compared with those of a well-matched lithotripsy-eligible group of 32 subjects treated with ursodiol alone (no lithotripsy). Pretreatment with ursodiol significantly improved while gallstone calcification interfered with fragmentation. Small gallstone size and number also aided fragmentation. Biliary lithotripsy plus ursodiol increased efficacy twofold compared with ursodiol therapy alone (47% vs. 22% of subjects gallstone free; P less than 0.02). Gallstones did not disappear in any subject with calcified gallstones (P less than 0.001) vs. lithotripsy). Product-limit analysis showed that the efficacy for gallstone dissolution increases in the following order: ursodiol alone, lithotripsy-ursodiol, lithotripsy-ursodiol pretreated with ursodiol (P less than 0.02, pairwise). Similar mean gallstone-dissolution rate constants (stone size divided by time to disappear) of stone fragments and whole gallstones during ursodiol therapy suggest that most fragments disappear by dissolution not expulsion. This finding explains why fragmentation appears to be the key predictor of disappearance and even partial fragmentation accelerates gallstone clearance. PMID- 1587423 TI - Liver pathology in genetic hemochromatosis: a review of 135 homozygous cases and their bioclinical correlations. AB - Liver pathology was assessed in 135 patients with well-defined genetic hemochromatosis ranging from mild disease to severe overload. Three lesions were clearly linked to iron-overload intensity--scarce sidero-necrosis, mild inflammation, and progressive fibrosis. Iron-free foci made of typical or dysplastic hepatocytes were found in 7.4% of the cases. An original grading allowed a reliable quantification of iron and the study of cellular and lobular distribution of iron, which permitted (a) the accurate identification of a decreasing iron gradient in hepatocytes from zone 1 to zone 3 in all cases, (b) the definition of a threshold hepatocytic/mesenchymal iron ratio related to the appearance of sidero-necrosis and to the development of fibrosis, and (c) demonstration that non-iron-related factors (mainly alcoholism) could shift iron from hepatocytes to sinusoidal cells without an increase in the total liver iron amount. This study provides a dynamic view of the iron overload process and suggests that sidero-necrosis and progressive sinusoidal iron overload play a role in the development of fibrosis in human genetic hemochromatosis. PMID- 1587424 TI - Portal hypertensive gastropathy in patients with cirrhosis. AB - Portal hypertensive gastropathy is a recently recognized important complication of cirrhosis. In the present study, the clinical features, portohepatic hemodynamics, and hepatic function were investigated in a series of 47 patients with cirrhosis. Mild gastropathy was found in 15 patients (32%) and severe gastropathy in 17 patients (36%). The presence of gastropathy seemed to be independent of age, sex, cause of cirrhosis, or grade of gastroesophageal varices. However, severe gastropathy was associated with an increase in portal venous pressure gradient (vs. control, P less than 0.01; vs. mild gastropathy, P less than 0.01), an increase in hepatic sinusoidal resistance (vs. control, P less than 0.01; vs. mild gastropathy, NS), and a decrease in hepatic blood flow (vs. control, P less than 0.01; vs. mild gastropathy, NS). In addition, patients with severe gastropathy had impaired metabolic activity of the liver, which was assessed by intrinsic clearance of indocyanine green (vs. control, P less than 0.01; vs. mild gastropathy, NS). These observations may have important therapeutic implications in patients with cirrhosis and portal hypertensive gastropathy. PMID- 1587425 TI - Sequence of morphological and hemodynamic changes of gastric microvessels in portal hypertension. AB - Changes in gastric microvasculature and blood flow at different phases of portal hypertension were studied in rats 1, 2, 3, 4, and 15 days after induction of portal hypertension or sham operation. Vessel lumen and vessel wall thickness were expressed as a ratio referred to the vessel size. On day 2 after constriction of the portal vein, gastric blood flow was decreased (0.57 +/- 0.06 vs. 0.99 +/- 0.20 mL.min-1.100 g-1; P less than 0.05), and gastric vessels had a distended lumen (0.42 +/- 0.02 vs. 0.28 +/- 0.03; P less than 0.01) and a thin wall (2.11 +/- 0.2 vs. 3.82 +/- 0.4; P less than 0.01). On day 4, the gastric blood flow of portal hypertensive animals was increased (1.15 +/- 0.14 vs. 0.71 +/- 0.07 mL.min-1.100 g-1; P less than 0.05), whereas gastric vessels had a reduced lumen (0.27 +/- 0.02 vs. 0.33 +/- 0.02; P less than 0.01) and a thick wall (4.19 +/- 0.52 vs. 3.16 +/- 0.30; P less than 0.05). By day 15, vessels with the largest lumens (0.45 +/- 0.01 vs. 0.29 +/- 0.01; P less than 0.01) and the thinnest walls (1.78 +/- 0.26 vs. 3.58 +/- 0.62; P less than 0.01) were observed in portal hypertensive animals. In conclusion, the gastric vessels of the 15-day portal vein-ligated rat resemble the structural abnormalities described in human portal hypertensive gastropathy. PMID- 1587426 TI - Effect of oral erythromycin on gallbladder motility in normal subjects and subjects with gallstones. AB - The action of the motilin receptor agonist erythromycin on human gallbladder contraction, measured by ultrasound, both in normal subjects and those with gallstone disease was studied. In 17 normal subjects, oral erythromycin administration (500 mg; vs. placebo) reduced fasting gallbladder volume at 2 hours (26.2 vs. 19.0 mL; P less than 0.001), and postprandial residual gallbladder volume (9.0 vs. 4.4 mL; P less than 0.001) and the rate constant of gallbladder emptying following the meal was significantly increased. Erythromycin also reduced fasting and residual gallbladder volumes in 13 patients with gallstone disease: in 6 who underwent cholecystolithotomy, fasting volume was 29.5 vs. 22.3 mL (P less than 0.05) and residual volume was 17.7 vs. 6.5 mL (P less than 0.05), and in 7 with gallstones in situ, fasting volume was 23.8 vs. 14.3 mL (P less than 0.05) and residual volume was 17.2 vs. 5.0 mL (P less than 0.05). In 7 of 8 subjects with gallstones and impaired gallbladder emptying, the gallbladder emptied normally following administration of erythromycin, and in 3 of the other 5 gallstone subjects gallbladder emptying was increased. In 6 normal subjects given erythromycin three times weekly for 1 month, the effect was maintained (fasting volume, 18.8 mL, P less than 0.001; residual volume, 3.7 mL, P less than 0.001). Oral erythromycin significantly reduces fasting and postprandial residual gallbladder volumes in both normal subjects and subjects with gallstones and reverses the gallbladder motility defect found in a proportion of subjects with gallstones. This effect is maintained for a month in normal subjects. PMID- 1587427 TI - Effects of long-term rifampicin administration in primary biliary cirrhosis. AB - The effects of rifampicin treatment (10 mg.kg-1.day-1) on pruritus and cholestasis were evaluated in 16 patients with primary biliary cirrhosis and pruritus followed up for 2-24 months. Assessment of pruritus severity, liver tests, aminopyrine breath test, and bile acids was done at 2 weeks and every 3 months after the beginning of the study. Two patients (12.5%) were withdrawn after 2 months of treatment because they had hepatitis caused by rifampicin. Four patients were withdrawn after 4 months because of liver transplantation (3 cases) and the development of leg edema associated with administration of rifampicin. The remaining 10 patients received therapy for 14.4 +/- 0.7 months and did not experience side effects. Pruritus improved in all patients and disappeared in 11 patients (79%) after 3 months of treatment. Moreover, all patients followed up for more than 1 year were free of pruritus. The alkaline phosphatase level decreased significantly, and the aminopyrine breath test results increased significantly after 2 weeks of treatment (P less than 0.001) and did not change thereafter. In the 9 patients treated for 15 months, alkaline phosphatase levels decreased to 63% of the basal levels and aminopyrine breath test results increased to 153% of baseline values. Transaminases, gamma-glutamyltransferase, and total bile salt levels decreased significantly after 2 weeks of treatment but returned to baseline after 3 months. No changes in bilirubin and cholesterol levels were observed. It is concluded that long-term rifampicin treatment is effective for relieving pruritus in primary biliary cirrhosis, but liver enzymes should be monitored to detect drug-induced hepatitis. PMID- 1587428 TI - Histopathology of membranous obstruction of the inferior vena cava in the Budd Chiari syndrome. AB - It is generally believed that membranous obstruction of the inferior vena cava in the Budd-Chiari syndrome is caused by congenital malformation. However, it does not explain the late onset of the disease. In the current study, hepatic portion of the inferior vena cava and hepatic veins were studied in 17 autopsy cases of the Budd-Chiari syndrome, 16 of which had no demonstrable cause (idiopathic). A sufficient amount of vena cava tissue was available for evaluation in 15 cases. Nine had membranous obstruction, with thickness varying from 3 to 8 mm. Thrombus formation was recognized in 7 of 9 cases. Occlusion of hepatic vein orifices of varying degree was present in 8 cases. In these occluding lesions, the basic structure of the venous wall was maintained. The intima was transformed into a fibrous laminar structure, and organized thrombi of varying ages were recognized; they were a mixture of fresh thrombi, organized thrombi, fibrous tissues, recanalizations, and calcifications. It is concluded that in these cases of the Budd-Chiari syndrome, occluding and stenosing lesions in the inferior vena cava and hepatic veins were thrombosis and its sequelae. There was no indication of congenital malformation. PMID- 1587429 TI - A controlled trial of interferon with or without prednisone priming for chronic hepatitis B. AB - In a randomized, controlled trial of recombinant interferon alfa-2b with or without prednisone priming in Chinese adults with chronic hepatitis B virus infection, stratified randomization for pretreatment serum alanine aminotransferase levels was done. Partial or complete antiviral responses were achieved in 17 (21.5%) of 79 treated patients and 3 (8.3%) of 36 controls (P = 0.14). The response to interferon treatment was significantly better in those who had elevated pretreatment transaminase levels and comparable to that reported in white patients [15 (38.5%) of 39 patients compared with 2 (5%) of 40 who had normal pretreatment transaminase levels (P = 0.0005)]. The spontaneous seroconversion rate was also higher among the controls with elevated transaminase levels [3 (18.8%) of 16 compared with 0 of 20 with normal transaminase levels], but this difference was not statistically significant (P = 0.16). Among the interferon-treated patients, prednisone priming appeared to have a marginal benefit over treatment with interferon alone in patients with elevated transaminase levels (43% vs. 33%), but not in those with normal transaminase levels (0% vs. 9.5%). It was confirmed that Chinese patients with normal transaminase levels respond very poorly to interferon alfa therapy. However, the response was significantly better in patients with elevated transaminase levels. PMID- 1587430 TI - Glycine cytoprotection during lethal hepatocellular injury from adenosine triphosphate depletion. AB - Glycine protects renal tubule cells from cell death during adenosine triphosphate (ATP) depletion. Although the liver plays a key role in glycine metabolism, information is lacking regarding the effects of glycine on lethal hepatocellular injury. Thus, the aim of this study was to determine the potential cytoprotective role of glycine during ATP depletion of rat hepatocytes. Metabolic inhibition with 2.5 mmol/L potassium cyanide (KCN) was used to produce ATP depletion. Hepatocyte suspensions treated with KCN had a 2-hour viability of 5.9% +/- 2.0%, whereas cells treated with KCN in the presence of 2.0 mmol/L glycine had a viability of 80.2% +/- 1.5%, which was virtually identical to controls (81.5% +/- 1.9%). Glycine cytoprotection was dose dependent and amino acid specific. The cytoprotective effect of glycine was not mediated by protein synthesis, glycine mitochondrial metabolism, cytosolic acidosis, or preservation of either intracellular cellular glutathione or ATP. However, glycine did decrease total cellular proteolysis by 18% +/- 2%, 25% +/- 3%, and 33% +/- 1% after 1, 2, and 3 hours of KCN treatment, respectively (P less than 0.01). Inhibition of proteolysis by glycine was dose dependent over the same range as its cytoprotection. The results suggest that glycine protects against hepatocellular injury by inhibiting degradative proteolytic activity. It was concluded that proteolysis may be an important mechanism contributing to lethal injury of hepatocytes during ATP depletion. PMID- 1587431 TI - Measurements of iron status in patients with chronic hepatitis. AB - Eighty patients with chronic viral hepatitis were screened for evidence of iron overload. Elevated serum iron values were noted in 36% of cases; serum ferritin values were above normal in 30% of men and 8% of women. Twenty-eight additional patients with chronic hepatitis for whom liver tissue was available for determination of iron content were evaluated to study the significance of iron overload in association with chronic hepatitis. Although 46% had elevated serum iron, ferritin, or transferrin-saturation levels, the hepatic iron concentration was elevated in only four cases, and the hepatic iron index was in the range for hereditary hemochromatosis (greater than 2.0) in only two of these. Serum aspartate aminotransferase activities correlated with serum ferritin levels in these patients, suggesting that ferritin and iron levels were increased in serum because of their release from hepatocellular stores associated with necrosis. Thus, in patients with chronic hepatitis in whom hereditary hemochromatosis is suspected, a liver biopsy should be performed with quantitation of hepatic iron and calculation of the hepatic iron index to confirm the diagnosis. PMID- 1587432 TI - Mineralocorticoid escape in patients with compensated cirrhosis and portal hypertension. AB - Failure to escape from mineralocorticoids in compensated cirrhosis is considered a major argument supporting the overflow theory of ascites. To assess the frequency and mechanism of mineralocorticoid escape in cirrhosis, 9-alpha fluorohydrocortisone (0.6 mg/day) was administered to 19 patients with compensated cirrhosis, portal hypertension, and no history of ascites who were able to maintain sodium balance on a 250 mmol Na+ diet. Fifteen patients (78.9%) escaped from mineralocorticoids, while 4 patients (21.1%) did not escape and developed ascites. Patients who did not escape had significantly higher cardiac index (4.97 +/- 0.42 vs 3.46 +/- 0.21 L.min-1.m-2) and lower peripheral vascular resistance (485.9 +/- 37.5 vs. 665.8 +/- 32.9 dyne.s.cm-5/m2) than those who escaped. Hepatic venous pressure gradient was not significantly different. The escape phenomenon was associated with a significant increase in mean arterial pressure, creatinine clearance, and atrial natriuretic factor and suppression of plasma renin activity. All of these parameters showed minimal or no changes in patients who did not escape. These results indicate that failure to escape from mineralocorticoids is uncommon in patients with compensated cirrhosis, is related to an inadequate expansion of effective plasma volume due to the accumulation of ascites, and occurs in patients with marked peripheral arteriolar vasodilation. PMID- 1587433 TI - Biotin transport in human liver basolateral membrane vesicles: a carrier mediated, Na+ gradient-dependent process. AB - The characteristics of biotin transport into human liver were examined using purified liver basolateral membrane vesicle (BLMV) preparations. Biotin uptake by BLMVs was mostly due to transport of the vitamin into the inside of vesicles. In the presence of an Na+ gradient (out greater than in), biotin transport with time was significantly higher than that in the presence of a K+ gradient and showed transient accumulation (overshoot). High concentrations of unlabeled biotin and related compounds caused significant cis inhibition in biotin transport in the presence of an Na+ (but not a K+) gradient. Transport of biotin as a function of concentration in the presence of an Na+ gradient included a saturable component, while it was lower and linear in the presence of a K+ gradient. Apparent Km and Vmax of the saturable Na+ gradient-dependent component were 1.22 mumol/L and 4.76 pmol.mg protein-1 x 10 s-1, respectively. Induction of a negative or positive intravascular potential using valinomycin-K diffusion methodology did not affect biotin transport into BLMVs. Also, neither the anion-exchange inhibitor 4,4' diisothiocyanatostilbene-2,2'-disulfonic acid nor 4-acetamido-4 isothiocyanostilbene-2,2'-disulfonic acid caused significant inhibition in biotin transport. These results indicate that biotin transport into human liver occurs via a specialized, carrier-mediated transport system. This system is Na(+) gradient dependent and transports the vitamin via an electroneutral process. PMID- 1587434 TI - Papillary bile duct dysplasia in primary sclerosing cholangitis. AB - A 62-year-old man with a 20-year history of chronic ulcerative colitis and a 9 year history of primary sclerosing cholangitis (PSC) underwent orthotopic liver transplantation because of symptoms related to PSC and cholangiographic features compatible with a biliary neoplasm. Study of the excised liver revealed papillary mucosal lesions in the common hepatic duct and the right and left hepatic ducts as well as cholangiectases and other features typically associated with PSC. The papillary lesions consisted of abundant fibrovascular stroma covered by biliary epithelium with low-grade and high-grade dysplasia. Some periductal glands were also dysplastic. These features distinguished papillary dysplasia from classic biliary papillomatosis. Only one focus of microinvasion was found; there were no metastases. Among 60 cases of PSC in whom the entire liver could be studied after orthotopic liver transplantation, this was the only instance of unequivocal dysplasia. However, in one specimen, papillary hyperplasia was found. Detailed macroscopic and microscopic rereview of 23 livers from our patients with the longest history of PSC (range, 5-24 years) failed to reveal any additional cases with dysplasia. It is concluded that (a) papillary mucosal lesions in PSC may represent papillary dysplasia without invasion; (b) these lesions may evolve from papillary hyperplasia; (c) the process may be largely, if not entirely, in situ; and (d) the prevalence of dysplasia and carcinoma of bile ducts may be less than the 7%-9% reported in the literature for malignancies associated with PSC. PMID- 1587435 TI - Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. AB - This report describes a patient in whom a severe vitamin E deficiency developed secondary to an intestinal malabsorptive disorder. In vivo and in vitro impairment of T-cell function, as well as a polyneuropathy, were observed in conjunction with this vitamin deficiency. Repletion of the vitamin deficiency was associated with marked improvement in the T-cell functions and modest improvement in the neuropathy. Observations in this patient suggest that severe vitamin E deficiency in humans may impair T-cell activity and that correction of the deficient state may reverse these T-cell abnormalities. Further studies will need to be performed to confirm these findings. PMID- 1587436 TI - Resolution of radiographic abnormalities with ursodeoxycholic acid therapy of primary sclerosing cholangitis. AB - Ursodeoxycholic acid therapy has shown encouraging results in relieving symptoms and decreasing liver biochemical abnormalities in patients with primary sclerosing cholangitis. However, established biliary strictures are generally considered irreversible. A case of primary sclerosing cholangitis with extensive intrahepatic biliary as well as pancreatic duct strictures that resolved to near normal on ursodeoxycholic acid therapy is reported. The implications of these findings are discussed. PMID- 1587437 TI - Prolonged cholestasis due to trimethoprim sulfamethoxazole. AB - Drug-induced liver injury due to trimethoprim sulfamethoxazole is rare and classified as an unpredictable or idiosyncratic type of hepatotoxic reaction. Early reports suggested that the pattern of liver injury in the majority of cases is mixed hepatocellular-cholestatic. The current report describes two cases of severe, prolonged cholestasis after treatment with trimethoprim sulfamethoxazole; intractable pruritus and abnormal liver test results lasted for 1-2 years after discontinuation of the drug. Liver biopsy specimens showed a cholestatic pattern of liver injury and only minimal hepatocellular necrosis or inflammation. Recent case reports suggest that cholestasis alone may occur after the use of trimethoprim sulfamethoxazole; these two additional cases show that cholestasis may be quite prolonged. PMID- 1587438 TI - Pancreatic stone predominantly composed of fatty acid calcium. AB - A 41-year-old man with chronic pancreatitis and pancreatic stones predominantly composed of fatty acid calcium is reported. He had complained of occasional abdominal pain for 10 years and visited the hospital because of a severe attack of abdominal pain. Laboratory data supported a diagnosis of pancreatitis. Computed tomography (CT) showed a high-density area in the head of the pancreas, and the CT number of this high-density area was lower than usual for pancreatic stones. Ultrasonography and endoscopic retrograde pancreatography showed a cystic lesion with small pancreatic stones in the head of the pancreas and irregular dilatation of the main pancreatic duct. Pancreaticojejunostomy and resection of pancreatic cyst were carried out for repeated episodes of abdominal pain under the diagnosis of chronic pancreatitis. The pancreatic stones obtained at surgery were proved to be mainly composed of fatty acid calcium after analysis of chemical composition of the stones. Fatty acid calcium was sometimes found in the biliary stones but never in the pancreatic stones. PMID- 1587439 TI - Development of thyroid disease during therapy of chronic viral hepatitis with interferon alfa. AB - Six of 237 (2.5%) patients with chronic viral hepatitis who were treated with recombinant interferon alfa developed thyroid disease while on treatment. Three patients developed hyperthyroidism, two of whom developed detectable levels of thyroid-stimulating immunoglobulin; three patients developed hypothyroidism in association with high titers of antithyroglobulin and/or antimicrosomal antibodies. The thyroid disease did not remit when interferon therapy was stopped, and all six patients required definitive therapy for the thyroid disease. These findings suggest that a small proportion of patients treated with interferon alfa develop autoimmune reactions and can develop autoimmune thyroid disease. PMID- 1587441 TI - Can diarrhea cause secondary steatorrhea? PMID- 1587440 TI - Primary sclerosing cholangitis and ulcerative colitis: potential cofactors in the dysplasia sequence. PMID- 1587443 TI - Further improvements in the surgical treatment of severe chronic constipation. PMID- 1587442 TI - Ocular complications of steroid use in pediatric patients--a lesson for gastroenterologists. PMID- 1587444 TI - Rapid induction of gluconeogenesis during fasting. PMID- 1587445 TI - Extrahepatic metabolic consequences of cirrhosis. PMID- 1587446 TI - Cytokine inhibition of gastric acid secretion--a little goes a long way. PMID- 1587447 TI - Quality of life and proctocolectomy. PMID- 1587448 TI - Gastric secretion in normal subjects. PMID- 1587449 TI - Basal acid output in gastroesophageal reflux disease. PMID- 1587450 TI - Suprahepatic inferior vena cava ligation to treat portal hypertension? PMID- 1587451 TI - Nutritional support in alcoholic liver disease--losing control(s)? PMID- 1587452 TI - Microlithiasis and cholesterolosis in 'idiopathic' acute pancreatitis. PMID- 1587453 TI - Polyethylene glycol 900: useful marker rather than notable exception. PMID- 1587454 TI - Bismuth absorption from the stomach and small intestine. PMID- 1587455 TI - Intestinal lymphangiectasia and antiplasmin therapy. PMID- 1587456 TI - Fumaric acid overproduction in yeast mutants deficient in fumarase. AB - A nuclear mutant of Saccharomyces cerevisiae deficient in mitochondrial fumarase has been identified through the in vitro biochemical assay of enzyme activity after visual selection due to an increased acidification ability of its colonies. Cells of the fumarase-deficient mutant fermenting glucose accumulated extracellular fumaric acid. This accumulation was observed only in growing cultures and required functional mitochondrial electron transport from succinate dehydrogenase to oxygen. PMID- 1587457 TI - tolQ is required for cloacin DF13 susceptibility in Escherichia coli expressing the aerobactin/cloacin DF13 receptor IutA. AB - We investigated the role of the tolQ gene in the import of cloacin DF13 across the outer membrane of Escherichia coli strains expressing the IutA receptor. The IutA outer-membrane protein is the receptor for the siderophore ferric aerobactin and also binds cloacin DF13, a bacteriocin produced by strains of Enterobacter aerogenes. In this report we present evidence that tolQ is required for the internalization of cloacin DF13 upon binding to IutA but it is not involved in the transport of ferric aerobactin. PMID- 1587458 TI - Failure to trigger the autolytic enzymes in minicells of Escherichia coli. AB - Minicells from Escherichia coli P678-54 are refractory towards procedures known to induce bacteriolysis of DNA-containing E. coli cells. Although still engaged in murein synthesis, minicells could not be lysed by penicillin G. Likewise, endogenous overproduction of the cloned soluble lytic transglycosylase, the predominant murein hydrolytic activity in E. coli, failed to lyse minicells. Furthermore, induction of the phage MS2 lysis protein, a hydrophobic protein assumed to trigger the autolytic system of the host, did not result in bacteriolysis. It is concluded that the murein hydrolases present in minicells are under a tight cellular control. PMID- 1587459 TI - Conjugal transfer of antibiotic resistances and plasmids from Campylobacter jejuni clinical isolates. AB - Six Campylobacter jejuni clinical isolates were examined for the occurrence of plasmids in association with antibiotic resistances as well as conjugal transfer. All the isolates were found to carry three similar plasmids of 78 kb, 12.6 kb and 3.3 kb in size. Multiple resistance to at least three of the antibiotics tested was observed with resistance to tetracycline most common. En bloc transfer of donor resistances at frequencies ranging from 10(-8) to 10(-4) were seen in all but one of the isolates during conjugation. The conjugal transfer of erythromycin, neomycin and streptomycin were observed to occur at frequencies similar to that of chloramphenicol, kanamycin and tetracycline. In isolate ABA94, three different antibiotic resistance phenotypes of the transconjugants were seen. In addition to en bloc transfer of the donor resistances, in approximately 10% of the transconjugants the streptomycin resistance was lost although these transconjugants carried the donor complement of three plasmids. In a further 1% of the transconjugants, resistance to kanamycin only was detected and these transconjugants did not carry any plasmids. PMID- 1587460 TI - Structure of the Escherichia coli 0104 polysaccharide and its identity with the capsular K9 polysaccharide. AB - The 0104 antigen (lipopolysaccharide, LPS) of Escherichia coli has an acidic O specific polysaccharide. From the aqueous phase of a phenol water extraction of E. coli O104: K-, a fraction was obtained by ultracentrifugation and Cetavlon precipitation of the supernatant, which was enriched in long-chain LPS. Compositional analysis, NMR spectroscopy, periodate oxidation and methylation analysis showed that the polysaccharide chain of O104 LPS II consisted of galactose, N-acetylgalactosamine and neuraminic acid and acetate in the molar ratio of 2:1:1:1 and contained 3-beta Gal, 3-beta GalNAc, 4-alpha Gal, and 4 alpha(9-OAc-NeuNAc) in linear sequence. The same results were obtained with the capsular K9 polysaccharide from E. coli O9:K9, as presented here and reported previously (Dutton et al. (1987) Carbohydr. Res. 170, 193-206). PMID- 1587461 TI - Bacterial uptake of octyl ethanolamine increases with pH. AB - The uptake of octyl ethanolamine (C8EA) by Pseudomonas pseudoalcaligenes was determined at pH 7.1-10.0. At pH 9.1 the total uptake was nearly three times higher and at pH 10.0 four times higher than at pH 7.1. Also the initial rate of uptake was lowest at pH 7.1. At pH 7.1 five to ten times higher concentrations of C8EA were needed than at pH 9.1 to achieve the same degree of leakage of cytoplasmic constituents. The results support the hypothesis that penetration of the bacterial cytoplasmic membrane by C8EA in its uncharged form is favoured. This takes place particularly with high pH in the suspending medium. In the cytoplasm, the pH is lower, and C8EA becomes more protonated. This will prevent back diffusion, promote accumulation and enhance membrane interaction and toxicity at high pH. PMID- 1587462 TI - Cloning and nucleotide sequence of the gene encoding the gamma-D-glutamyl-L diamino acid endopeptidase II of Bacillus sphaericus. AB - The gene encoding the Bacillus sphaericus gamma-D-glutamyl-L-diamino acid endopeptidase II, a cytoplasmic enzyme involved in cell sporulation [1], contains the information for a 271-amino acid protein devoid of a signal peptide. The endopeptidase lacks sequence relatedness with other proteins of known primary structure except that its C-terminal region has significant similarity with the C terminal region of the 54-kDa P54 protein of Enterococcus faecium, of unknown function [2]. PMID- 1587463 TI - Surface components of HeLa cells that inhibit cytadherence of Chlamydia trachomatis. AB - Isolated HeLa plasma membrane (PM) preparations and extracts containing either cell-surface proteins or lipids were examined for inhibition of adherence of radiolabeled Chlamydia trachomatis serovar E elementary bodies to glutaraldehyde fixed HeLa monolayers. A dose-dependent adherence-inhibitory activity could be demonstrated with the PM. A urea extract as well as lipids from HeLa cells also inhibited chlamydial cytadherence. The inhibitory activity of the PM was trypsin sensitive. It was absent when the urea extract was prepared from trypsin-treated HeLa cells. The urea extract was subjected to electrophoresis and protein blotting using a native gel system. Probing with radiolabeled chlamydial cytadhesin showed a single protein present in the urea extract that could represent a HeLa cell protein receptor for the chlamydiae. PMID- 1587464 TI - A natural mutant of plasmid RP4 that confers phage resistance and reduced conjugative transfer. AB - A natural isolate of RP4 (PRC#116) acquired from the Stanford University Plasmid Reference Center differed from the wild-type Incompatibility Group P plasmid in several respects. Cells of Escherichia coli harboring PRC#116 were resistant to the IncP pili-specific bacteriophage PRD1 and GU5, and transferred this plasmid at a lower efficiency than the wild-type RP4. Phage sensitivity was restored, and transfer considerably improved in PRC#116+ bacteria transformed with plasmid constructs containing the origin of transfer (oriT region) of RP4. Mutant RP4 plasmids equivalent to PRC#116 were selected at a high frequency from an RP4+ E. coli population infected with PRD1 indicating that this RP4 variant may be the product of a very common mutation of the wild-type plasmid. PMID- 1587465 TI - The chicken in history and in the soup: II. Thank you Columbus. PMID- 1587466 TI - Latex allergy: its importance in clinical practice. AB - Latex has been identified as a potent and significant allergen. Atopic medical and dental personnel who regularly use latex gloves and patients with chronic latex exposure are at increased risk of latex allergy. If this allergy is unrecognized, anaphylactic shock can occur as a result of mucosal latex absorption at the time of surgery or procedure. Use of a nonlatex glove can prevent this potentially fatal event. Latex anaphylaxis also can occur from absorption through disrupted skin in occupationally exposed patients. Further prospective studies are needed to look at the significance of a positive latex skin test, particularly in the history-negative population. Only then can we define appropriate screening procedures. PMID- 1587467 TI - Latex hypersensitivity: two case reports. AB - For persons hypersensitive to latex, continued exposure may result in a life threatening situation. Since 1979 reports appeared supporting evidence of urticaria, rhinitis, asthma, and anaphylaxis in association with latex exposure. We present two cases of latex hypersensitivity, patients who reacted to latex on skin-prick and radioallergosorbent tests (RAST). A 30-year-old surgeon developed reactions to latex gloves. On skin-prick testing to latex extract in saline, he was 4+. RAST latex antigen-specific IgE was 50.75 times control. The second case is that of a 24-year-old nurse who underwent multiple corrective surgeries for congenital birth defects and experienced reactions to latex. On skin-prick testing to an extract of latex in saline, she was 2+. RAST latex antigen-specific IgE was 23.37 times control. Both patients were given epinephrine and diphenhydramine and advised to use latex-free gloves and to avoid latex products. As health care personnel contact with latex products increases because of new guidelines for the prevention of sexually transmitted diseases, more adverse reactions in this subpopulation will occur. PMID- 1587468 TI - Detection of IgG4 and IgE antibodies to rubber proteins by immunoblotting in latex allergy. AB - Sera from four latex-allergic hospital employees (two physicians and two nurses) were examined for the occurrence of IgG4 and IgE antibodies to rubber proteins by immunoblotting. We used natural rubber sap as antigen source and detected IgG4 antibodies in all four patient sera. The IgG4 antibodies bound to 12 rubber protein antigens with molecular weights ranging from 14 kD to 53 kD. IgE antibodies bound nine of the antigens and the major antigen for both IgG4 and IgE seemed to be a 21 kD rubber protein. The parallel occurrence of IgG4 and IgE antibodies against the same rubber protein antigens suggests that IgG4 antibodies also may play a role in the pathogenesis of latex allergy. PMID- 1587469 TI - Latex allergy: another occupational risk for physicians. PMID- 1587470 TI - Delayed nasal mucociliary clearance in patients with nonallergic rhinitis and nasal eosinophilia. AB - This study investigated nasal mucociliary clearance as related to nasal eosinophilia in nonallergic rhinitis patients using the technique of nasal saccharin challenge. Fifty-six consecutive patients with nonallergic rhinitis were evaluated with nasal cytology and saccharin challenge. A saccharin challenge time of greater than 25 minutes was considered abnormal. Twelve of 56 patients (21.4%) had nasal eosinophilia. Fifteen of 56 patients (26.8%) had prolonged nasal circulation times greater than 25 minutes, indicating delayed mucociliary clearance. Although 7 of 12 patients (58.3%) with nasal eosinophilia had delayed mucociliary clearance, only 8 of 44 patients (18.2%) without eosinophilia had circulation times longer than 25 minutes. The correlation of nasal eosinophilia with prolongation of the nasal circulation time is statistically significant (chi square 5.84, P = .0156). We postulate that damage to the nasal mucociliary system may be an etiologic factor for a subset of patients with nonallergic rhinitis and that this damage may be mediated by eosinophils. PMID- 1587471 TI - Stevens-Johnson syndrome (SJS): effectiveness of corticosteroids in management and recurrent SJS. AB - To confirm that corticosteroids are beneficial in the treatment of Stevens Johnson syndrome (SJS), 15 patients with the syndrome were evaluated by the same group of physicians over 2 years. All patients had cutaneous and most had mucosal lesions. Patients were treated with corticosteroids ranging from prednisone 40 mg daily to methylprednisolone 750 mg daily. The same group of physicians participated in the management of these patients until recovery. No deaths occurred among the 15 patients. Recovery was complete in all cases, and there was no residual skin, mucosal, or visceral damage except for minimal scarring in one patient. In some cases, reversal of disease after onset of corticosteroid therapy was sufficiently dramatic to demonstrate a benefit. The use of corticosteroids in the treatment of SJS remains controversial. We conclude that corticosteroids are beneficial in treatment of the syndrome. They may be lifesaving in some patients and should be the standard of therapy. SJS should be considered to be erythema multiforme with either bullous lesions or visceral involvement or both. PMID- 1587472 TI - Discovery and rediscovery. PMID- 1587473 TI - Sequence of the bacteriophage SP01 gene 30. AB - The bacteriophage SP01 gene 30, whose function is essential for DNA synthesis, has been analyzed for its primary structural features. Conditionally lethal mutations in the gene 30 locus have been mapped and sequenced, and the wild-type amino acid (aa) sequence has been deduced along with that of a co-transcribed and possibly co-translated upstream unidentified reading frame (URF). The aa sequence deduced for gene 30 shares partial similarity with protein P of bacteriophage lambda, which participated in lambda DNA replication, and also with the exonuclease, gp46, of bacteriophage T4. A lysine-rich region of the hypothetical product of the URF shares similarity with both the T4 DNA topoisomerase and the phi 29 gene 3-encoded protein; the latter codes for a terminal protein which participates in the priming of DNA elongation. PMID- 1587474 TI - Modular expression and secretion vectors for Bacillus subtilis. AB - A modular vector system has been developed for the extracellular production of heterologous proteins in Bacillus subtilis. This modular vector system consists of four secretion vectors which are based upon the genes encoding the Bacillus amyloliquefaciens extracellular alkaline protease, neutral protease, barnase and levansucrase. The modular vectors contain compatible restriction sites downstream from the signal peptide-coding region. Three reporter proteins (staphylococcal protein A, levansucrase and Escherichia coli alkaline phosphatase) that offer complementary advantages for cloning, genetic manipulations and media optimization have been fused to the various signal peptides. These secretion vectors function in E. coli and hence can be used to compare the mechanisms of protein secretion in E. coli and B. subtilis. PMID- 1587475 TI - Cloning and sequencing the Lactobacillus brevis gene encoding xylose isomerase. AB - The gene (xylA) coding for the Lactobacillus brevis xylose isomerase (Xi) has been isolated and its complete nucleotide sequence determined. L. brevis Xi was purified and the N-terminal sequence determined. All attempts to directly clone the intact xylA using a degenerative primer deduced from amino acids (aa) 10-14 were not successful. A fragment coding for the first 462 bp from the 5' end of xylA was isolated by PCR with two primers, one coding for aa M36 to W43 and the second coding for an aa sequence (WGGREG) conserved in a number of Xi's isolated from other bacteria. From the sequence of this fragment, two additional PCR primers were synthesized, which were used in an 'outward' reaction to clone a 546 bp fragment including a region upstream from the N terminus. Finally, the complete xylA gene was cloned in a 0.43-kb NlaIII-SalI fragment and a 1.9-kb SalI EcoRI fragment. The 449-aa sequence for the L. brevis Xi shows homology with Xis isolated from other bacteria, especially within the primary catalytic domains of the enzyme. PMID- 1587476 TI - Overexpression of the Thermus aquaticus B malate dehydrogenase-encoding gene in Escherichia coli. AB - Expression of the Thermus aquaticus B malate dehydrogenase (MDH)-encoding gene (mdh), cloned in Escherichia coli, was initially at a relatively low level (0.1% of soluble cell protein) and was effected by read-through from the tac promoter in the plasmid vector used. An enhancement in expression to 0.4% of soluble cell protein was achieved by shortening the intervening sequence between the promoter and the translation start codon of mdh. An NdeI restriction site (5'-CAT-ATG-3') was engineered in the shortened fragment, which also changed the start codon from GTG to ATG. This resulted in an eightfold increase in expression, to 3.2% of soluble cell protein. Expression was further increased by subcloning the mdh gene via the engineered NdeI site, into two plasmid expression vectors, one carrying the E. coli trpP promoter and the other the E. coli mdhP promoter. In both these expression systems, 40-50% of the soluble cell protein was T. aquaticus MDH. This suggests that expression of the cloned T. aquaticus mdh in E. coli is enhanced predominantly by the optimisation of transcription and translation initiation signals. Moreover, the base composition of the coding region and the pattern of codon usage dictated by it appear to have little effect on expression. Heat treatment of the cell extract at 85 degrees C further effected purification of T. aquaticus MDH to over 80% of the soluble cell protein. The MDHs purified to homogeneity from the high-expression clones were identical with the MDH isolated from T. aquaticus B cells with respect to all measured parameters. PMID- 1587477 TI - A putative second adenylate kinase-encoding gene from the yeast Saccharomyces cerevisiae. AB - Sequencing of the region upstream from the yeast RAD3 gene has revealed an open reading frame (ORF) of 225 amino acids (aa) that could encode a 25.3-kDa polypeptide. The predicted aa sequence of this ORF is homologous with that of several eukaryotic adenylate kinase (Adk)-encoding genes, including the yeast gene, ADK1. These findings suggest that the yeast Saccharomyces cerevisiae has a second Adk-encoding gene, tentatively designated as ADK2. PMID- 1587478 TI - A type-III DNA restriction and modification system in Bacillus cereus? PMID- 1587479 TI - Palindromic Haemophilus DNA uptake sequences in presumed transcriptional terminators from H. influenzae and H. parainfluenzae. AB - We have found palindromic pairs of near matches to the 11-bp Haemophilus DNA uptake motif shortly after the stop codons of three Haemophilus genes. Short runs of thymidylate residues follow the stem-loop structures thus defined. This organization suggests that, in H. influenzae, the uptake motif may be preferentially incorporated into gene termination signals, as has been proposed for Neisseria gonorrhoeae. PMID- 1587480 TI - A homologue of the ras-related CDC42 gene from Schizosaccharomyces pombe. AB - A cDNA was isolated from the fission yeast, Schizosaccharomyces pombe, using mixed oligodeoxyribonucleotides encoding part of the GTP-binding site of the ras superfamily. The encoded protein is the homologue of the budding yeast CDC42 gene product and the human proteins, CDC42Hs and G25K. PMID- 1587481 TI - Cloning and sequencing of Pseudomonas genes determining sodium dodecyl sulfate biodegradation. AB - The nucleotide sequences of two genes involved in sodium dodecyl sulfate (SDS) degradation, by Pseudomonas, have been determined. One of these, sdsA, codes for an alkyl sulfatase (58,957 Da) and has similarity (31.8% identity over a 201 amino acid stretch) to the N terminus of a predicted protein of unknown function from Mycobacterium tuberculosis. The other gene, sdsB, codes for a positive activator protein (33,600 Da) that has extensive similarity with the lysR family of helix-turn-helix DNA-binding activator proteins. PMID- 1587482 TI - Regulation of the protein A-encoding gene in Staphylococcus aureus. AB - The synthesis of several exoproteins, including protein A (SpA) in Staphylococcus aureus is coordinately regulated by the agr locus. Different constructs of the SpA-encoding gene (spa) were introduced into Agr+ and Agr- derivatives of a spa- strain of S. aureus. Plasmid-located spa with deletions at the 3' end expressed a truncated SpA which was almost exclusively extracellular and which confirmed the role of C-terminal region X in cell-wall binding. In the Agr- host, the production of SpA was elevated severalfold. Transcriptional and translational fusions were constructed to study the agr- mediated regulation of spa gene expression. Translational fusions of a beta-lactamase (Bla)-encoding ApR reporter gene with the spa promoter and N-terminal coding sequences expressed elevated levels of Bla activity in the Agr- host. In contrast, a transcriptional fusion of the spa gene with a promoter of the positively regulated staphylococcal epidermolytic toxin A (ETA)-encoding gene synthesized higher levels of SpA in an Agr+ host, as compared to Agr-. Moreover, the synthesis of SpA in the Agr+ strain was switched on during the transition from the exponential to stationary phase in a similar fashion to ETA itself. These data strongly indicate that the regulation of both SpA and ETA occurs at the transcriptional level in S. aureus. The agr regulated spa promoter was defined by deletion analysis and by transcript mapping. PMID- 1587483 TI - A coding region segment is necessary, but not sufficient for rapid decay of the HIS3 mRNA in yeast. AB - In Saccharomyces cerevisiae, the HIS3 (encoding imidazoleglycerolphosphate dehydratase) mRNA is unstable (t1/2 = 7 min), whereas the ACT1 (encoding actin) mRNA is more stable (t1/2 = 30 min). To define determinants responsible for rapid mRNA decay, hybrid genes comprised of various regions of these two mRNAs were constructed, transformed into yeast on centromere-containing vectors, and the half-lives of the resultant chimeric mRNAs were measured. To examine whether the 3'-untranslated region (3'-UTR) of HIS3 can confer instability to the ACT1 mRNA, DNA encoding the 3'-UTR of ACT1 was replaced with the corresponding region of HIS3. The hybrid mRNA containing the HIS3 3'-UTR decayed at a rate similar to the endogenous ACT1 mRNA. The mRNA containing the HIS3 5'-UTR and most of the HIS3 coding region fused to an ACT1 3'-fragment was unstable, indicating that HIS3 instability determinants are located within the HIS3 5'-UTR or coding sequence. Deleting 411 nucleotides (nt) from the coding region of either HIS3 or the 5' HIS3-ACT1-3' chimeric gene resulted in a three- to fourfold stabilization of the respective mRNAs. However, insertion of this 411-nt fragment in-frame into the entire ACT1 gene had no destabilizing effect on the resultant hybrid mRNA. We conclude that the instability determinants of HIS3 mRNA are complex, involving a coding region segment and, possibly, the 5'-UTR. PMID- 1587484 TI - Isolation and characterization of two novel ras superfamily genes in Saccharomyces cerevisiae. AB - We have isolated two novel genes, designated as RHO3 (on chromosome IX) and RHO4 (on chromosome XI), belonging to the ras superfamily, from the yeast Saccharomyces cerevisiae. Deletion of RHO4 did not affect cell growth, but deletion of RHO3 caused a severe growth delay and a decrease in cell viability. The rho3 and rho4 disrupted genes displayed synthetic lethality at 30 degrees C. RHO3 and RHO4 seem to have overlapping functions in cell growth, because the growth defect in rho3 cells was suppressed by overexpression of RHO4 despite the low homology (about 35%) at the amino acid sequence level between the RHO3 and RHO4 proteins. PMID- 1587485 TI - Versatile shuttle vectors and genomic libraries for use with Schizosaccharomyces pombe. AB - We have constructed a variety of pUC-based vectors designed for maintenance in Schizosaccharomyces pombe. These can be used for both gene bank construction and subcloning. Plasmids pUR18 and pUR19 are modifications of pUC vectors containing the Sc. pombe ars1 and ura4 sequences and retaining the lacZ XGal blue-white selection system for screening for DNA inserts. These vectors have been used to construct representative Sc. pombe and Saccharomyces cerevisiae genomic libraries. To assist in the creation of gene deletions, we have constructed another two plasmids. Combined with the technique of partially filling-in 5' overhangs created with restriction enzymes, these plasmids simplify the replacement of all or part of an open reading frame by a functional ura4 gene. Furthermore, such constructs can be excised with SfiI as a linear fragment for use in Sc. pombe transformations. When integrated into the Sc. pombe genome, the site of integration can be easily mapped by pulsed-field gel electrophoresis using the presence of a novel NotI site. PMID- 1587486 TI - Cloning and sequencing of the alcohol oxidase-encoding gene (AOD1) from the formaldehyde-producing asporogeneous methylotrophic yeast, Candida boidinii S2. AB - Alcohol oxidase (AOD) is the first key enzyme for methanol metabolism in methylotrophic yeasts. AOD activity is strictly regulated by carbon source. The AOD1 gene was cloned from a gene library of the asporogenous formaldehyde producing methylotrophic yeast, Candida boidinii S2. The complete nucleotide sequence of the gene and its 5'- and 3'-flanking regions (4174 bp) were determined. To identify the conserved and divergent sequences of the AOD1 gene and its 5'-flanking sequences among different species of methylotrophic yeasts, the AOD-encoding genes from C. boidinii S2 (AOD1), Hansenula polymorpha (MOX) and Pichia pastoris (AOX1 and AOX2) were compared. In addition to conserved amino acid sequences, several DNA segments in the G+C-rich region of 5'-flanking sequences were also found to be conserved. Northern analysis showed that the AOD1 gene transcript was induced by methanol, but was not detected when cells were grown on ethanol or glucose. Thus, as in ascosporogenous methylotrophic yeasts, AOD1 gene expression in C. boidinii appears to be controlled at the RNA level. PMID- 1587487 TI - Gene rIII is the nearest downstream neighbour of bacteriophage T4 gene 31. AB - The nucleotide sequence of the 2218-bp T4 DNA fragment encompassing gene 31 and five complete open reading frames (ORFs) is presented. We show here that one of these ORFs, ORF31.-1, located downstream from gene 31, is the rIII gene. The position of the gene was established by comparison with the sequences of the rIII gene mutants, r67, rES40 and rBB9. The ORF corresponding to the rIII gene encodes a basic protein of 82 amino acids with an M(r) of 9323 and a pI of 9.28. According to the Chou and Fasman [Adv. Enzymol. 47 (1978) 45-148] secondary structure prediction, the rIII protein has a relatively high helical content. In addition, discrepancies with the overlapping sequences determined by other authors in this region are indicated. PMID- 1587488 TI - Cellular 'neurothekeoma': an epithelioid variant of pilar leiomyoma? Morphological and immunohistochemical analysis of a series. AB - Cellular neurothekeoma is a recently recognized benign cutaneous neoplasm, which is currently regarded as being of nerve sheath origin and is thought to represent a variant of conventional neurothekeoma (dermal nerve sheath myxoma). Nine new cases presenting predominantly in adolescents or young adults are described. Morphologically they were characterized by short fascicles or small nests of palely eosinophilic epithelioid or spindle-shaped cells which ramified in an ill defined manner between dermal collagen bundles. Myxoid matrix was absent or sparse. Scattered normal mitoses and multinucleate giant cells were often present. Immunohistochemically all nine cases were strongly NK1/C3 positive, seven were weakly NSE positive and three were smooth muscle actin positive. Staining for S-100 protein, PGP 9.5, epithelial membrane antigen and desmin was negative in all cases. In view of its distinctive architecture and immunophenotype, both of which are totally different from conventional neurothekeoma, it is proposed that cellular 'neurothekeoma' is a separate discrete entity which may represent an epithelioid variant of pilar leiomyoma. PMID- 1587489 TI - The palisaded, encapsulated neuroma (solitary circumscribed neuroma). AB - We describe the clinical and pathological features of 41 palisaded encapsulated neuromas. They present as small, solitary, asymptomatic papules, predominantly on the face in middle age. No case had co-existent neurofibromatosis or multiple mucosal neuromas. Histologically, they have distinctive features, consisting of a proliferation of Schwann cells and large numbers of axons within a perineurial derived capsule, permitting simple and reliable distinction from schwannomas and neurofibromas. Overall, the palisaded encapsulated neuroma accounts for approximately 25% of all nerve sheath tumours of the dermis. True schwannomas rarely occur in the dermis. Despite their original name, many cases are incompletely encapsulated and we support the recent proposal to rename these lesions solitary circumscribed neuroma. PMID- 1587490 TI - Is poor prognosis really related to HLA-DR expression by malignant melanoma cells? AB - HLA-DR expression was examined in 50 consecutive primary cutaneous malignant melanomas with a Breslow depth greater than 2 mm using two well-characterized monoclonal antibodies which detect fixation-resistant epitopes. In 31 of these cases (62%) a subpopulation of tumour cells was reactive, although there was considerable heterogeneity. Positive labelling did not correlate with depth but was associated with a reduced likelihood of developing early metastatic disease and a tendency for better overall survival, particularly in male patients. These findings contrast with earlier studies using cryostat sections and one study on paraffin-embedded tissue in which HLA-DR expression was shown to be a poor prognostic factor, but are consistent with the findings in other malignant tumours studied. The significance of HLA-DR expression as a marker of prognosis may depend on the type of tissue preparation, the sensitivity of the immunocytochemical techniques used and the method of assessment. PMID- 1587491 TI - Pagetoid infiltration in primary cutaneous melanoma. AB - Pagetoid infiltration of the epidermis by melanocytes, also termed 'buckshot spread', is regarded by some as being essential for the confident histopathological diagnosis of primary cutaneous melanoma. We have reviewed 340 melanomas received over a 23 year period to assess the frequency of pagetoid infiltration and whether its presence bears any relationship with other histopathological features. Conspicuous pagetoid infiltration was present in 32.1% of the lesions and occasional melanocytes were observed within the stratum spinosum in a further 23.5% of cases. However, no melanocytes could be seen above the basal layer in 44.4% of the melanomas. The presence of pagetoid infiltration showed inverse correlation with tumour thickness, level of invasion, growth phase and mitotic count, and positive correlation with the presence and severity of regression. No association was found with the site of the primary lesion, melanocytic dysplasia or lentigo maligna in the adjacent epidermis, or with the presence of residual benign naevus cells in the epidermis. Thus, pagetoid infiltration of the epidermis was commonest in in situ or thin horizontal growth phase melanomas, and was conspicuous in only one-third of cases. While its presence is useful in the diagnosis of melanoma, its absence should not preclude it. PMID- 1587492 TI - Distribution of the cytoskeletal protein beta-tubulin in normal lung, cryptogenic fibrosing alveolitis and lung tumours. AB - Tubulin is the major protein of microtubules. The immunocytochemical distribution of tubulin within the human respiratory tract has not been investigated in detail and no analysis of diseased lung or lung tumours has been undertaken. We therefore studied the distribution of beta-tubulin in formalin-fixed normal lung (n = 6), cryptogenic fibrosing alveolitis (n = 10) and lung tumours (n = 66), using a monoclonal antibody to beta-tubulin. In normal lung positive immunostaining was observed in all ciliated epithelium from the trachea down to bronchiolar level; blood vessel endothelium, vascular smooth muscle and nerve bundles were also strongly positive; pneumocytes, cartilage and airway smooth muscle gave weak staining. A similar distribution of beta-tubulin was seen in cryptogenic fibrosing alveolitis, but with strong tubulin immunostaining of fibroblasts in the interstitium and of the cytoplasm of ciliated respiratory epithelial cells. In lung tumours, six of 17 (35%) adenocarcinomas, one of two adenosquamous and one of 17 (5%) squamous cell carcinomas gave strong immunostaining. All six large cell carcinomas gave strong immunostaining for tubulin. In neuroendocrine tumours, two of seven (28%) carcinoids, two of seven (28%) atypical carcinoids and seven of 10 (70%) small cell carcinomas were strongly positive for tubulin. beta-Tubulin is widely distributed in the normal and diseased respiratory tract and is found in many lung tumours, particularly in large cell and small cell carcinomas which are highly aggressive in behaviour. PMID- 1587493 TI - Malignant transformation in a pyloric adenomyoma: a case report. PMID- 1587494 TI - Diffuse pulmonary ossification--a rare complication of tuberculosis. PMID- 1587495 TI - Recurrent and subsequently metastasizing Merkel cell carcinoma in a 7-year-old girl. PMID- 1587496 TI - Epithelioid variant of solitary circumscribed neuroma of the skin. PMID- 1587497 TI - Fatal bronchial stenosis due to isolated relapsing chondritis. PMID- 1587498 TI - Granulomatous enterocolitis associated with therapeutic irradiation. PMID- 1587499 TI - Leiomyosarcoma with osteoclast-like giant cells. PMID- 1587500 TI - Jejunoileal bypass and extreme adaptive mucosal hyperplasia. PMID- 1587501 TI - Nodular regenerative hyperplasia of the liver in Behcet's disease. PMID- 1587502 TI - Histopathology for minor surgery. PMID- 1587503 TI - Basaloid-squamous carcinoma of the upper aerodigestive tract. PMID- 1587504 TI - General physicians' limited role in mental health care. PMID- 1587505 TI - A perspective on the attention-deficit disorders. PMID- 1587506 TI - AIDS and victims of sexual assault. PMID- 1587507 TI - What we know about homelessness among mentally ill persons: an analytical review and commentary. AB - Although extensive research on the homeless mentally ill population has been conducted, existing studies have failed to answer three important questions: the prevalence of chronic mental illness among homeless persons, whether deinstitutionalization has precipitated increased homelessness in this population, and what kinds of services should be offered. The author suggests that future research will require clearer definition of the terms used in discussing this population and calls for increased federal direction in making policies to respond to their problems, especially the problems of those who are geographically mobile. Successful service planning must address the full array of disabilities experienced by homeless mentally ill persons, including psychiatric symptoms, secondary responses to the experience of illness, and disabilities resulting from stigma and lack of societal opportunity. PMID- 1587508 TI - A quality improvement process for state mental health systems. AB - Continuous improvement of the quality of patient care is a major goal in state mental health systems, most of which operate several large hospitals and many community mental health centers geographically dispersed across the state. Although each facility may have an adequate quality assurance program, many opportunities for improvement are lost without integration of these efforts into a unified, statewide quality improvement system. The authors describe development of such a system in South Carolina and give examples of improvements in patient care that have taken place since the program was initiated in 1987. The activities of the central office of quality assurance include collecting and analyzing data about adverse incidents in state facilities, monitoring corrective actions, conducting annual surveys of operations at all state facilities, and investigating and coordinating resolution of complaints about patients' rights. PMID- 1587509 TI - Improving quality assurance through psychiatric mortality and morbidity conferences in a university hospital. AB - To make quality assurance more outcome oriented, the department of psychiatry in a university hospital developed a program of psychiatric mortality and morbidity conferences for reviewing cases with undesirable outcomes. The conference combines aspects of a traditional medical mortality and morbidity conference with features of utilization review and risk management. Case review is focused on mortality, morbidity, or specific indicators developed by the departmental services involved and on a determination of whether an adverse outcome was avoidable, possibly avoidable, or unavoidable. The authors summarize the 100 cases reviewed in the first seven months. They believe the focus on outcome gives the method a useful role in quality assurance; advantages include its recognizable contributions to continuing education and training. PMID- 1587510 TI - Developing family planning services for female chronic mentally ill outpatients. AB - The family planning needs of chronic mentally ill women outpatients, many of whom do not use contraceptives and are at high risk for unwanted pregnancies, have been rarely addressed. Taking a thorough sexual history is the first step in assessing patients' need for family planning services. Patient education, including instruction about physiological processes and contraceptive methods and assertiveness training, is the most important service component. Offering family planning services in the mental health center has many advantages, including better communication between mental health care providers and family planning specialists about patients' special needs and enhanced opportunities for integrating family planning with other programs such as parenting classes, substance abuse treatment, and services for preventing sexually transmitted diseases. PMID- 1587511 TI - Family planning for women with bipolar disorder. AB - Women with bipolar disorder often ask their treating clinician for information about family planning, as they are concerned about the impact of their illness on offspring. Three areas that should be included in discussions with patients and their partners are heritability of the disorder, risks during pregnancy, and risks during the postpartum period. The author summarizes information about genetic transmission of bipolar disorder, effects on bipolar patients of stress associated with pregnancy and childrearing, and effects of medication on the fetus and newborn. Discussion of these issues is most relevant for a women patient who is planning a pregnancy, but may also be useful for couples before marriage, for a women patient who finds that she is pregnant, and for men with bipolar disorder who want to become fathers. PMID- 1587512 TI - Assessment of risk behaviors for HIV infection among psychiatric inpatients. AB - A 13-item questionnaire was constructed to assess risk factors for HIV infection among 476 patients newly admitted over a one-year period to a state psychiatric hospital in New York City. Because psychopathology can affect patients' self reports, the validity of the instrument was established by HIV antibody tests in a subset of 352 patients. Results of the questionnaire indicated that the 352 patients were almost equally divided between the high-risk and low-risk categories. HIV seroprevalence was .6 percent among the low-risk patients, but 14.4 percent among the high-risk patients. The findings suggest that a screening program to detect HIV-positive patients should be undertaken in this population, that it should be focused on the high-risk subgroup, and that the questionnaire can be used to define that subgroup. However, results of the study may not generalize to other geographic areas. PMID- 1587513 TI - High needs and low priority of mentally ill residents of adult homes. AB - Adult homes are a major residential resource for persons with serious mental illness. Although many adult homes provide sub-standard care and receive inadequate clinical support, little effective long-term action is taken to improve conditions. This paper describes factors that interact to create inertia in the adult home industry. They include a lack of effective regulatory agencies, unrealistic reimbursement policies, service delivery roles so broadly defined that they reduce the homes' power to complete for resources, clinicians' lack of identification with the industry, the scarcity of effective case management and service advocacy programs, and poor data bases. The interaction of these factors prevent owners of adult homes, other human service providers, and government agencies from establishing self-sustaining corrective mechanisms. PMID- 1587514 TI - Mental retardation and psychiatric illness. AB - Although traditional diagnostic criteria are accepted for use with mentally retarded persons, diagnosis of psychiatric disorders in this population is often complicated by clinicians' ignoring or underestimating such disorders and by patients' communication problems. The revision of DSM-III and changes in policies of third-party payers have sensitized clinicians to the presence of psychopathology among mentally retarded persons. The authors discuss the relationship between mental illness and mental retardation and review recent research on the diagnosis of specific psychiatric disorders in these patients. Some problems, such as behavioral disruptiveness, psychoses, and phobias, are more prevalent among mentally retarded persons than among other populations, whereas other problems, such as alcoholism and suicide, may be less common. PMID- 1587515 TI - Training psychiatric residents in the diagnosis and treatment of mental illness in mentally retarded persons. AB - A serious shortage of psychiatrists trained to care for mentally retarded patients exists. Based on a successful program that has been in place for more than a decade, the authors offer guidelines for training psychiatric residents in the diagnosis and treatment of mental illness in mentally retarded persons. They describe a model curriculum and suggest ways to modify existing four-year curricula. Special diagnostic skills for working with this population, such as posing questions in concrete terms and ruling out the effects of disabilities like seizure disorders, are reviewed. Important treatment issues include knowing the side effects of neuroleptics and understanding the stages through which families and other caregivers pass in accepting a person's mental retardation. PMID- 1587516 TI - Violence against staff by mentally retarded inpatients. PMID- 1587517 TI - A hierarchy of aggressive and violent behaviors among psychiatric inpatients. PMID- 1587518 TI - Decreasing excessive water drinking by chronic mentally ill forensic patients. PMID- 1587519 TI - Polydipsia with hyponatremia in a state hospital population. PMID- 1587520 TI - Medical disorders among young acutely ill psychiatric patients in a military hospital. PMID- 1587521 TI - Crowding and the fiscal crisis. PMID- 1587522 TI - Psychiatry in Zimbabwe. PMID- 1587524 TI - Differential termination of primer extension: a novel, quantifiable method for detection of point mutations. AB - We have developed a novel technique that is useful for the rapid detection of previously characterized point mutations in the human genome. The method relies on the differential termination of primer extension being performed simultaneously on normal and mutant template molecules in the presence of a selectively limited complement of deoxynucleotide triphosphates. We have used this technique to determine the carrier status of two potential carriers of a hemophilia B mutation at codon 145 in the factor IX gene. In addition, the technique has been used to quantify the levels of mutant sequence in several tissues of a hemophilia B patient who is a somatic mosaic for a point mutation at codon 350. PMID- 1587523 TI - Risk calculations for hereditary effects of ionizing radiation in humans. AB - A prediction of the extent to which an additional dose of ionizing radiation increases the natural germ cell mutation rate, and how much such an increase will affect the health status of future human populations is part of the service that human geneticists are expected to offer to human society. However, more detailed scrutiny of the difficulties involved reveals an extremely complex set of problems. A large number of questions arises before such a prediction can be given with confidence; many such questions cannot be answered at our present state of knowledge. However, such predictions have recently been attempted. The 1988 report of the United Nations Scientific Committee for the Effects of Atomic Radiation and the fifth report of the Committee on Biological Effects of Ionizing Radiation of the US National Research Council have presented a discussion of the human genetics problems involved. Empirical data from studies on children of highly radiation-exposed parents, e.g. parents exposed to the atomic bombs of Hiroshima and Nagasaki, or parents belonging to populations living on soil with high background radiation, have been mentioned in this context. Whereas precise predictions are impossible as yet because of deficiencies in our knowledge of medical genetics at various levels, the bulk of the existing evidence points to only small effects of low or moderate radiation doses, effects that will probably be buried in the "background noise" of changing patterns of human morbidity and mortality. PMID- 1587525 TI - Molecular characterization of genetic mutations in human lactate dehydrogenase (LDH) B (H) variant. AB - We have previously detected a single base substitution of G by A at the Arg codon CGC in exon 4 of the mutant lactate dehydrogenase (LDH) gene, an unstable LDH-B variant (case 1). Here, we use the polymerase chain reaction (PCR) to amplify genomic DNA of two cases (the original case 1 and a new patient, case 2). We were able to confirm that case 1 is homozygous for the mutation, causing a replacement of the conserved Arg by His at residue 173. The resulting LDH-B variant subunit is unstable in vivo. Whereas the mutation in exon 4 was not observed in case 2, a different single base substitution of A by C was detected at the Ser codon AGT in exon 3. This mutation causes a replacement of the conserved Ser by Arg at residue 131. Genomic analysis of the family of case 2 by mismatched PCR showed that the missense mutation was consistent with their biochemical phenotypes. The replacement results in a conformational change of the residues near the Ser, probably because the side chain of Arg is much more bulky than that of Ser. The change may affect the arrangement of the cofactor binding site and result in the loss of enzyme activity. The experimental observations are consistent with computer graphics analyses. PMID- 1587526 TI - Detection of multiple cystic fibrosis mutations by reverse dot blot hybridization: a technology for carrier screening. AB - We describe the implementation of a modified version of the reverse dot blot hybridization technology to detect eight cystic fibrosis mutations. The method is simple, quick, reliable, inexpensive, and nonradioactive and utilizes the sensitivity of the polymerase chain reaction coupled with colored or chemiluminescent substrates for mutation detection. We have used this system in a clinical laboratory to identify the delta F508, G542X, G551D, R553X, 621 + 1G--- T, W1282X, N1303K, and 1717G----A mutations. The technique is practical for genotyping individuals at many potential mutation sites, as in cystic fibrosis and beta-thalassemia, in which over 95 mutations can cause disease. This technology appears to be the method of choice for the widespread carrier screening of multiple cystic fibrosis mutations. PMID- 1587527 TI - The polymorphism ApoB/4311 in patients with myocardial infarction and controls: the ECTIM Study. AB - The polymorphism affecting codon 4311 of the apolipoprotein B gene (ApoB/4311) was investigated in a large case-control study in two French and one Northern Irish geographically defined populations. Cases were recruited 3 to 9 months after a myocardial infarction (MI) and controls were randomly selected from the population. The polymorphism was assessed using allele-specific oligonucleotides (ASO). The genotype frequencies of the ApoB/4311 polymorphism did not differ in Northern Ireland and France and were in Hardy-Weinberg equilibrium in all groups; strong associations with three other polymorphisms of the ApoB gene (XbaI, EcoRI, VNTR(34 repeats)) were observed and it was possible to identify highly sensitive and specific markers of the ApoB/4311 rare variant. Homozygotes for the ApoB 4311 rare variant were slightly less frequent in cases than in controls: 22 (4.4%) and 35 (6.7%) respectively (population adjusted chi 2 = 3.3 P less than 0.07), especially in Belfast: 6 (3.1%) and 12 (7.6%), respectively (P less than 0.06). Several lipid and lipoprotein parameters were measured. Consistently among control groups, rare homozygotes had lower mean levels of ApoB (P less than 0.02), triglycerides (P less than 0.02), and lipoprotein particles containing ApoE and ApoB (LpE:B; P less than 0.001) and a higher mean level of lipoprotein particles containing ApoAI and not ApoAII (LpAI; P less than 0.02) than heterozygotes and frequent homozygotes combined. The strong association between the ApoB/4311 polymorphism and LpE:B was also observed in patients with MI. When present in the homozygous form, the ApoB/4311 Asn----Ser variant is associated with a lipoprotein profile that is apparently favourable. PMID- 1587528 TI - Cytogenetic studies in motile sperm from normal men. AB - Most studies on human sperm chromosomes from normal men involve the heterologous fertilization of zona free hamster eggs by unselected human sperm. In this work, we have performed cytogenetic studies of highly motile sperm, selected by a swim up method. A total of 505 motile human sperm complements from three normal donors was analysed. The total frequency of sperm with chromosomal abnormalities (10.9%; 6.9% structural aberrations and 4.0% aneuploidy) and the sex ratio (50.4% X:49.6% Y) were similar to those obtained from whole semen samples. Our results indicate that the selection of motile sperm does not imply chromosomal selection. PMID- 1587529 TI - Repair of human sperm chromosome aberrations in the hamster egg. AB - In order to study the repair capacity of fertilized hamster eggs for the lesions present or induced in human sperm, we have examined the potentiating effect of caffeine, a DNA repair inhibitor, on the frequency and types of sperm chromosome aberrations. Sperm samples were donated by an individual treated with chemotherapy for a testicular cancer 3 years previously. Exposure of spermatozoa and inseminated oocytes to caffeine led to an increase of sperm chromosome aberrations, indicating that the damage to human sperm can be repaired in untreated hamster egg cytoplasm. The potentiating effect of caffeine was mainly reflected in an increase of unrejoined aberrations, indicating that the formation of chromosomal rearrangements is also inhibited. Since both chromatid-type and chromosome-type aberrations increase after treatment with caffeine, damage to human sperm can probably be repaired inside the hamster egg cytoplasm by pre- and post-replication repair mechanisms. PMID- 1587530 TI - Polymerase chain reaction amplification of two polymorphic simple repeat sequences within the von Willebrand factor gene: application to family studies in von Willebrand disease. AB - We have used the polymerase chain reaction to amplify two variable number of tandem repeats (VNTRs) within a region of repetitive DNA located in intron 40 of the von Willebrand factor (vWf) gene. Heterozygosity for VNTR I was observed in 30 out of 39 normal unrelated individuals tested (77%), and for VNTR II in 29 out of 44 (66%) similar individuals. Family studies were carried out on 11 kindreds with von Willebrand disease (vWD). Ten of these families were found to be informative for one or other of the VNTRs or for a combination of data from both VNTRs. This method can be used for antenatal diagnosis and for carrier diagnosis in recessive forms of vWD. It is also useful for tracking the gene associated with vWD in type I families where there may be one or more individuals with a phenotypically uncertain diagnosis. PMID- 1587531 TI - A new polymorphism of thyroxin-binding globulin in three African groups (Mali) with endemic nodular goitre. AB - The thyroxin-binding globulin (TBG) polymorphism was investigated in three African groups: two belonged to the Bwa villages of Mali, and the third was a Dogon group living in the same area. The Bwa groups were characterized by the occurrence of nodular goitres, whereas the Dogon population did not show similar pathological symptoms. Females were more affected by goitre than males in the affected villages. The TBG polymorphism enabled us to demonstrate the presence of an undescribed allele (TBG C1) in these populations. The frequency of the TBG S allele was also higher than previously published in other African groups. We observed a disequilibrium in the distribution of the C and S alleles in the population, with an excess of homozygous TBG S individuals. No clear relationship between the TBG polymorphism and the number of nodules can be drawn. PMID- 1587532 TI - Estimation of the male and female mutation rates in Duchenne muscular dystrophy (DMD). AB - We present the results of an international collaborative study aimed at estimating the ratio of male to female mutation rates in Duchenne muscular dystrophy based on the method of C. Muller and T. Grimm. With a sample size of 295, this ratio is found to be very close to 1, thus giving evidence for equal mutation rates in males and females in Duchenne muscular dystrophy. PMID- 1587533 TI - Multipoint linkage analysis of the short arm of chromosome 11 in non-insulin dependent diabetes including maturity onset diabetes of youth. AB - Members of three families with maturity onset diabetes of youth (MODY) and seven with "common" type 2 diabetes were typed for six DNA markers (H-RAS, INS, HBBC, PTH, CALC1, CAT) on the short arm of chromosome 11. Using conventional pairwise linkage analysis, close linkage in the MODY families was excluded for all six markers. By multipoint analysis and a genetic map of the short arm of chromosome 11, MODY was excluded from a region of at least 35 and up to 60 centiMorgans (cM) on the short arm of chromosome 11. Multipoint analysis in the type 2 families also excludes linkage to the INS, H-RAS region of at least 3 and up to 30 cM. This study using multipoint linkage analysis in non-insulin dependent diabetes provides strong evidence against a role for mutations in or around the insulin gene in the causation of MODY or type 2 diabetes in the families studied. PMID- 1587534 TI - Expression of RPS4X in fibroblasts from patients with structural aberrations of the X chromosome. AB - A series of fibroblasts from patients with numerical or structural aberrations of the X chromosome were scored for the amount of mRNA of ribosomal protein S4 (RPS4X). Haplo-insufficiency of this gene has been reported previously to be a possible cause of Turner syndrome. Our results show that the transcription rate of RPS4X correlates with the number of gene copies. This confirms earlier findings indicating that this gene escapes X inactivation. In addition, we demonstrate that this applies to structurally aberrant X chromosomes. Our results show that RPS4X does not give rise to a type of haplo-insufficiency in these cases, because it escapes inactivation, even on structurally aberrant X chromosomes from patients with Turner syndrome. We therefore assume that RPS4X is not the most prominent candidate gene for Turner syndrome. PMID- 1587535 TI - Evidence for an ancestral alphoid domain on the long arm of human chromosome 2. AB - In situ hybridization, under low stringency conditions with two alphoid DNA probes (pY alpha 1 and p82H) labeled with digoxigenin-dUTP, decorated all the centromeres of the human karyotype. However, signals were also detected on the long arm of chromosome 2 at approximately q21.3-q22.1. Since it is supposed that human chromosome 2 originated by the telomeric fusion of two ancestral primate chromosomes, these findings indicate that not only the telomeric sequences, but also the ancestral centromere (or at least its alphoid sequences), have been conserved. PMID- 1587536 TI - Absence of p53 germ-line mutations in bilateral breast cancer patients. AB - The cause of Li-Fraumeni syndrome, a rare group syndrome of familial cancers, has recently been identified. Patients with this inherited condition are highly susceptible to specific neoplasms, including early-onset breast cancers. The available evidence links Li-Fraumeni syndrome to inherited mutations of the tumor suppressor gene p53. Moreover, somatically acquired p53 mutations and gene deletions are common feature in breast cancer of sporadic origin. These findings suggest that germline p53 mutations are important in familial and, possibly sporadic, breast tumors. We have therefore screened lymphocyte DNA from 19 unrelated bilateral cancer patients for germline p53 mutations in exons 5, 6, 7 and 8. We have however detected no germline mutations by means of the single strand confirmation polymorphism technique in any of the lymphocyte DNAs examined and conclude that p53 mutations are not generally involved in bilateral breast cancer. PMID- 1587537 TI - Strategies in vaccine development. PMID- 1587538 TI - Controlled-release vaccines--biodegradable polylactide/polyglycolide (PL/PG) microspheres as antigen vehicles. PMID- 1587539 TI - Vaccinia recombinants as vaccine vectors. PMID- 1587540 TI - Advances in mycobacterial genetics: new promises for old diseases. PMID- 1587541 TI - Mucosal immunity: implications for vaccine development. AB - The mucosal surfaces in e.g. the gastrointestinal, respiratory and urogenital tracts represent a very large exposure area to exogenous agents including microorganisms. Not surprising, therefore, those mucosal tissues are defended by a local immune system with properties and functions that in many respects are separate from the systemic immune system. The intestine is the largest immunological organ in the body. It comprises 70-80% of all immunoglobulin producing cells and produces more secretory IgA (SIgA) (50-100 mg/kg body weight/day) than the total production of IgG in the body (ca. 30 mg/kg/day). The local immune system of the gut has two main functions: to protect against enteric infections, and to protect against uptake of and/or harmful immune response to undergraded food antigens. The best known entity providing specific immune protection for the gut is the SIgA system. The resistance of SIgA against normal intestinal proteases makes antibodies of this isotype uniquely well suited to protect the intestinal mucosal surface. The main protective function of SIgA antibodies is the "immune exclusion" of bacterial and viral pathogens, bacterial toxins and other potentially harmful molecules. SIgA has also been described to mediate antibody-dependent T cell-mediated cytotoxicity (ADCC), and to interfere with the utilization of necessary growth factors for bacterial pathogens in the intestinal environment, such as iron. It is now almost axiomatic that in order to be efficacious, vaccines against enteric infection must be able to stimulate the local gut mucosal immune system, and that this goal is usually better achieved by administering the vaccines by the oral route rather than parenterally. Based on the concept of a common mucosal immune system through which activated lymphocytes from the gut can disseminate immunity also to other mucosal and glandular tissues there is currently also much interest in the possibility to develop oral vaccines against e.g. infections in the respiratory and urogenital tracts. It has previously been widely assumed that only live vaccines would efficiently stimulate a gut mucosal immune response. However, an oral cholera vaccine, composed of the nontoxic B subunit of cholera toxin in combination with killed whole cell (WC) cholera vibrios has been shown to stimulate a strong intestinal SIgA antibody response associated with long-lasting protection against cholera. We have used this new cholera subunit vaccine and developed ELISPOT methods for examining at the clonal B and T cell level the dynamics of intestinal and extra intestinal immune responses in humans after enteric immunizations.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1587542 TI - Vaccination against acute respiratory virus infections and measles in man. AB - Several viruses may cause more or less severe acute respiratory infections in man, some of which are followed by systemic infection. Only for influenza and measles are licensed vaccines available at present. The protection induced by influenza vaccines, which are based on inactivated whole virus or viral subunits, depends largely on the matching of vaccine strain and circulating virus. Measles vaccines, which are based on attenuated live virus, have been quite effective in controlling the disease in vaccinated populations in the industrialized world. In developing countries, severe measles infections occur in infants from six to nine months of age, which necessitates the vaccination of children of less than six months. At that time maternal antibodies, that may interfere with the induction of protection, may still be present. Therefore, instead of using the parenteral route, the possibility to use the mucosal route of primary immunization is also investigated for vaccination with attenuated live measles vaccines. The use of inactivated measles vaccines has resulted in a state of immunity which upon exposure to the virus may induce an atypical measles syndrome including a severe pneumonia. Measles virus proteins presented in an iscom matrix have recently been shown to induce functional B and T cell responses to both the surface glycoproteins of the virus. These responses could also be induced in the presence of virus neutralizing antibodies and they proved to be protective in several animal model systems. Many of the problems that have been encountered in the development of measles vaccines, proved to be similar in the development of vaccines against other paramyxoviruses causing acute respiratory infections in man, including respiratory syncytial virus. Parenteral application of inactivated and attenuated live vaccines against these paramyxoviruses has generally had little success. Topical application of attenuated live vaccines has been more successful, and also the use of vaccinia recombinant viruses expressing foreign paramyxoviral glycoproteins has shown promising results in laboratory animals. Live vaccines based on adenovirus types 4 and 7 in oral enteric-coated vaccines, which lead to virus replication in the intestines but not in the respiratory tract have been included in military vaccination programs. The possibility to replace e.g. the E3 region with foreign DNA makes adenoviruses also suitable as cloning vectors for proteins of other respiratory viruses. Although live attenuated vaccines against some of the serotypes of rhinoviruses have shown promising results, the generation of a multivalent vaccine against this epidemiologically most significant cause of acute respiratory infections will be almost impossible, due to the multiplicity of serotypes involved.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1587543 TI - Vaccination against HIV. AB - The spread of AIDS progresses unrelentingly despite all efforts of public education and the only real hope of epidemiological control lies in the development of an effective vaccine. The very nature of the AIDS virus (HIV) and the manner with which it interacts with the host makes development of a practical vaccine very difficult. Recent successes using whole inactivated virus as immunogen in the SIVmac animal model system now show that it is possible to protect against infection. However, due to supposed limited efficacy in the field of such a vaccine and the fact that large scale production and administration of a multi-shot whole HIV-based product would be technically impossible, it is now important to identify which of the proteins are responsible and which immune response is protective. With this knowledge a recombinant or synthetic vaccine could be produced on a large scale. However, despite recent protection of a few chimpanzees against HIV infection itself there is currently no proven effective and practical vaccine even in the laboratory and it will be many years before such a product is available to the general public. PMID- 1587544 TI - Vaccination against tuberculosis and leprosy. PMID- 1587545 TI - Development and clinical testing of an acellular pertussis vaccine containing genetically detoxified pertussis toxin. AB - In 1924 Ramon described the inactivation of diphtheria toxin by formaldehyde treatment. This method allowed the introduction of mass vaccination against diphtheria and tetanus and opened the way to the inactivation of viruses by chemical treatment. In this review we describe the use of genetic manipulations for the inactivation of pertussis toxin. The toxin inactivated by this new method is an antigen superior to those obtained by chemical treatment and has been used to develop a new vaccine against whooping cough. PMID- 1587546 TI - Vaccination against malaria. PMID- 1587547 TI - Immunity and the prospects for vaccination against filariasis. PMID- 1587548 TI - Vaccine strategies against schistosomiasis. PMID- 1587549 TI - Molecular characterization of the variable regions of a mouse polyreactive IgG2b antibody with rheumatoid factor activity. AB - The complete nucleotide sequences of heavy and light chains of a mouse polyreactive IgG2b antibody were determined. This antibody, obtained after primary immunization of BALB/c mice with human lymphoblastoid cells, possess anti HLA-DR and anti-rheumatoid factor activities and reacts with various self and nonself antigens. The VL and VH segments were found to belong to the VK8 and VH7183 families, respectively. The VH segment shared a high percentage of sequence similarity (95%) with previously described germline genes. The VK segment had 98.9% of sequence similarity with a consensus sequence VK8 of antibodies with anti-phosphorylcholine activity. Furthermore, the framework regions 2 and 3 of the VL segment were very similar to the framework regions 2 and 3 of other antibodies known to possess rheumatoid factor activity. We postulate that during immunization, the presence of HLA-DR antigens selects precursors having configurations similar to that of the germline, and induces some somatic mutations that do not significantly affect antibody polyreactivity. PMID- 1587550 TI - Genetic control of streptococcus-induced hepatic granulomatous lesions in mice. AB - Hepatic granulomatous lesions were induced in mice by a single intraperitoneal injection of 3 mg of disrupted Streptococcus pyogenes cell-wall material. Mice carrying the H-2b or H-2k haplotypes were highly susceptible to the induction and three weeks after the injection produced numerous granulomas. In contrast, mice of the H-2d haplotype were resistant and produced only a few hepatic granulomas. Resistance was inherited as a dominant trait and in the backcross generation segregated together with the H-2d phenotype. Testing of the H-2-recombinant mice indicated that the putative gene(s) determining resistance/susceptibility is located to the right of the S and to the left of the D region. This location corresponds to the recently described gene cluster consisting of tumor necrosis factor (TNF) and lymphotoxin genes and several BAT sequences. The known effect of TNF on granuloma formation in mice is consistent with a possible effect of TNF genes, and their variants, on S. pyogenes-inducibility of hepatic granulomas in mice. PMID- 1587551 TI - Activation of Lyt-2 associated with distant upstream insertion of an SL3-3 provirus. AB - Two Lyt-2+ mutants of the T-cell lymphoma SL12.4.10 were selected by fluorescence activated cell sorting. Both mutants expressed Lyt-2 (CD8 alpha-chain) but not Lyt-3 (CD8 beta-chain). Derivatives of one Lyt-2+ mutant that expressed Lyt-3 could be isolated by sorting for Lyt-3+ cells. Southern blotting analysis indicated that both mutants had structural rearrangements within or immediately 3' of the Lyt-3 gene, accompanied by demethylation of at least one Hpa II site within the Lyt-2 gene. Gene cloning analysis of one mutant demonstrated that the structural rearrangement was due to insertion of an SL3-3 provirus 35 kb 5' to the Lyt-2 gene. It is likely that Lyt-2 gene activation is a direct or indirect consequence of proviral insertion at this site. PMID- 1587552 TI - Allelic diversity at the primate major histocompatibility complex DRB6 locus. AB - The HLA-DRB6 gene (also called DRB sigma/V1) has been found only in about 26% of human HLA haplotypes, i.e.; DR1, DRw10, and DR2-bearing ones (Corell et al. 1991). In contrast, exon-2 DRB6 sequences have been obtained from all tested primates: nine chimpanzees (Pan troglodytes), three gorillas (Gorilla gorilla) and three orangutans (Pongo pygmaeus); other apes which had already been sequenced (one gorilla and one chimpanzee) also had the DRB6 gene. Thus, all apes tested from three different species, some of them evolutionary separated by at least 14-16 million years, bear the DRB6 gene. In addition, more than one gene copy per haplotype has been found in one chimpanzee; this, together with the apparent loss of this gene in some of the human DR haplotypes, may indicate that the DR genome has undergone evolutionary changes more recently and more actively than class I or III genes. In addition, ten different and presumably allelic DRB6 exon-2 sequences have been obtained, and some of them coming from different species are more similar to each other than the one from the same species; this finding goes in favor of the trans-species theory of major histocompatibility complex polymorphism generation. Also, data are presented supporting that DRB6 may be one of the eldest genes of the DRB family, thus one of the first to diverge from the ancestral DRB gene. PMID- 1587554 TI - AB1: a novel HLA-DPB1 allele found in one third of an Australian population. PMID- 1587555 TI - Regulation of Thy-1 gene expression by the methylation of the 5' region of Thy-1 gene and intracellular regulatory factors in immature B cells. AB - In c mu- B220+ Thy-1- FL2-52-2, an immature B cell line transformed with a temperature-sensitive mutant of Abelson murine leukemia virus(ts OS-59), Thy-1 antigen expression was induced after the shift of the culture temperature from a permissive(35 degrees C) to a non-permissive temperature(39 degrees C), and a Thy 1+ subclone, FL2-52-2-1 was isolated by limiting dilution. Furthermore, since a population of Thy-1+FL2-52-2-1 lost Thy-1 antigen expression during culture at a non-permissive temperature, Thy-1- FL2-52-2-1-1 was isolated from the cultured cells. Methylation analysis by Southern blotting experiments showed that 5' region of the Thy-1 gene was methylated in Thy-1- FL2-52-2 but demethylated in Thy-1+ FL2-52-2-1 and Thy-1-FL2-52-2-1-1. To determine whether or not there exist intracellular regulatory factors responsible for Thy-1 gene expression, Thy-1a allele was transfected into Thy-1(Thy-1.2-) FL2-52-2 and Thy-1- FL2-52-2-1-1. The transfected Thy-1a allele was expressed in Thy-1- FL2-52-2, but not in Thy-1- FL2 52-2-1-1, indicating the presence of the intracellular regulatory factors requisite for Thy-1 gene expression in Thy-1- FL2-52-2. It appeared that in Thy-1 FL2-52-2-1-1, Thy-1 gene was not expressed because of the absence of the intracellular regulatory factors although the 5' region of the Thy-1 gene was demethylated. These results indicated the existence of at least two regulatory mechanisms of Thy-1 gene expression in immature B cells: methylation of the 5' region of the Thy-1 gene and intracellular regulatory factors. PMID- 1587553 TI - Trans-species evolution of Mhc-DRB haplotype polymorphism in primates: organization of DRB genes in the chimpanzee. AB - The DRB region of the human major histocompatibility complex displays length polymorphism: Five major haplotypes differing in the number and type of genes they contain have been identified, each at appreciable frequency. In an attempt to determine whether this haplotype polymorphism, like the allelic polymorphism, predates the divergence of humans from great apes, we have worked out the organization of the DRB region of the chimpanzee Hugo using a combination of chromosome walking, pulsed-field gel electrophoresis, and sequencing. Hugo is a DRB homozygote whose single DRB haplotype is some 440 kilobases (kb) long and contains five genes. At least one and possibly two of these are pseudogenes, while three are presumably active genes. The genes are designated DRB*A0201, DRB2*0101, DRB3*0201, DRB6*0105, and DRB5*0301, and are arranged in this order on the chromosome. The DRB2 and DRB3 genes are separated by approximately 250 kb of sequence that does not seem to contain any additional DRB genes. The DRB*A0201 gene is related to the DRB1 gene of the human DR2 haplotype; the DRB2*0101 and DRB3*0201 genes are related to the DRB2 and DRB3 genes of the human DR3 haplotype, respectively; the DRB6*0105 and DRB5*0301 genes are related to the DRBVI and DRB5 genes of the human DR2 haplotype, respectively. Thus the Hugo haplotype appears to correspond to the entire human DR2 haplotype, into which a region representing a portion of the human DR3 haplotype has been inserted. Since other chimpanzees have their DRB regions organized in different ways, we conclude that, first, the chimpanzee DRB region, like the human DRB region, displays length polymorphism; second, some chimpanzee DRB haplotypes are longer than the longest known human DRB haplotypes; third, in some chimpanzee haplotypes at least, the DRB genes occur in combinations different from those of the human haplotypes; fourth, and most importantly, certain DRB gene combinations have been conserved in the evolution of chimpanzees and humans from their common ancestors. These data thus provide evidence that not only allelic but also haplotype polymorphism can be passed on from one species to another in a given evolutionary lineage. PMID- 1587556 TI - Anti-Sm autoantibodies of systemic lupus erythematosus cross react with dietary plant proteins. AB - Cross reactivity of patient lupus autoantibodies to the small nuclear ribonucleoprotein particles of many different types of animals is well documented. The aim of our research was to determine if any level of cross reactivity existed between proteins of common dietary plants and anti-Sm autoantibodies of lupus patient's sera, as has been found for scleroderma patient sera (Agris et al., Exptl. Cell Res. 189, 276-279, 1990). Protein extracts from soy bean, corn, spinach, and carrot were analyzed. At least one protein (molecular weight approximately 28,000 daltons) common to all the above protein extracts was recognized by most of the anti-Sm sera tested. Affinity purified antibody eluted from the 28 kilodalton plant protein specifically recognized the Sm proteins of a HeLa cell protein extract. Recognition of the 28 kilodalton dietary plant protein was found to be unique to anti-Sm lupus sera. PMID- 1587557 TI - Effect of temperature on the expression of major histocompatibility complex class I antigens. AB - In the present study we investigated the effect of temperature on MHC class-I gene expression in BALB/C 3T3 cells incubated for 5 days at 34 degrees C, 37 degrees C and 39 degrees C. FACS analysis revealed no significant difference in the cell surface expression of any of the 3 major class-I antigens at 34 degrees C and 37 degrees C. Strikingly, however, when the level of the respective mRNA was determined, only that of the H-2K was comparable at both temperatures, whereas the levels of the H-2D and H-2L mRNA were profoundly higher at 37 degrees C. These data appear to reflect a differential temperature-related transcriptional control of the different class-I genes or a different temperature effect on the stability of their mRNA. The absence of a parallel increase in surface expression of the corresponding H-2D and H-2L antigens may result from some translational or post-translational limiting factors. At 39 degrees C, however, these limiting factors seem to be overcome since the surface expression of all the 3 antigens was remarkably increased although the level of their encoding mRNA was rather lower than in 37 degrees C. This stimulatory effect might be ascribed to heat shock proteins which are known to arise in cells at heat or other stress conditions. They participate in assembly and disassembly of various protein complexes and in transport of certain proteins across intracellular membranes. Such proteins may have arisen in our cells at 39 degrees C and facilitated the intracellular assembly of the class-I molecules and their transport to the cell surface. The possible implication of such heat shock proteins in the anti-tumor effect of hyperthermia is discussed. PMID- 1587558 TI - Corynebacterium parvum can reverse the depression of macrophage hydrogen peroxide production caused by erythrocyte phagocytosis. AB - Our previous studies have shown that the phagocytosis of IgG-coated erythrocytes (EIgG) in vivo increases the mortality rate with bacterial infection, and EIgG phagocytosis in vitro depresses phorbol myristate acetate (PMA)-triggered H2O2 production. The present study was undertaken to determine if the depression of H2O2 production caused by EIgG phagocytosis could be reversed by exposing macrophages to priming agents. Macrophages exposed to 100 micrograms/ml of C. parvum, it's pyridine-soluble extract (PE), or the pyridine extract residue (PER) for 1 hr showed an enhanced production of H2O2 in response to PMA triggering. The priming effect of C. parvum, PE, and PER lasted for 3-6 hr. 18 hr after exposure to C parvum or PER, PMA-triggered H2O2 production was depressed, however PE did not have this effect. The priming effect of C parvum was not prevented by cycloheximide. EIgG phagocytosis caused a dose dependent depression of PMA triggered H2O2 production. When macrophages were exposed to C. parvum, PE, or PER following EIgG phagocytosis, the priming of PMA-triggered H2O2 production was reduced but H2O2 production was maintained at levels equal to or greater than that of control macrophages. These results show that phagocytosis did not prevent the action of priming agents on macrophage respiratory burst capacity, and suggests that such agents may preserve macrophage bactericidal function following phagocytosis. PMID- 1587559 TI - Correlation between the prevalence of serum HBV DNA and immunoserologic HBV markers in the subjects with or without hepatitis. AB - The prevalence of serum HBV DNA, detected by polymerase chain reaction, and that of immunoserologic HBV markers (HBsAg, HBeAg, anti-HBs, and anti-HBc), determined by immunoassays, were compared among three groups of subjects: (A) chronic active hepatitis B patients, (B) chronic asymptomatic HBV carriers, and (C) normal individuals. Except five of the normal individuals, all of the subjects are positive for anti-HBc while some of them were also positive for other immunoserologic HBV markers, such as anti-HBs, HBsAg, and HBeAg. Serum HBV DNA were detected in 81% in group A, 52% in group B, and 20% in group C. In both group A and B, serum HBV DNA were detected in all the subjects with anti HBc+/HBsAg+/HBeAg+. However, the percentage of seropositive HBV DNA in the subjects with anti-HBc+/HBsAg+ in Group A was much higher than that in Group B. Interestingly, the percent of serum HBV DNA+ in the individuals with anti-HBc+ only was markedly higher than that in the subjects with anti-HBc+/anti-HBs+ in both Group A and C, suggesting that anti-HBs may play a role in the inhibition of HBV replication and clearance of HBV virion from blood. Above serological profiles will provide important information concerning the significance of serum HBV DNA detection in judgement of HBV replication in the individuals with or without HBV infection. Cautions should be taken to clarify those so called normal individuals who have no symptoms of hepatitis B, no HBsAg in the sera and normal transaminase, but have HBV replication in their bodies. PMID- 1587560 TI - Integration of accident specialists and specialties. PMID- 1587561 TI - Trauma: today's problems, tomorrow's answers. PMID- 1587562 TI - Treatment of ipsilateral supracondylar and forearm fractures in children. AB - The treatment of ipsilateral supracondylar fractures of the humerus and fractures of the forearm bones was evaluated in 11 children. After an average of 6 years, 10 children had excellent or good results and one had a poor result from Volkmann's ischaemic contracture. Displaced supracondylar fractures of the humerus associated with distal fractures of the forearm bones are best treated by closed reduction and percutaneous pin fixation of the humeral fracture and a below-elbow plaster backslab. PMID- 1587563 TI - External fixation for diaphyseal femoral fractures: a benefit to the young child? AB - External fixation for the treatment of diaphyseal femoral fractures in children seems an attractive alternative, which explains why its application gets more and more advocates. Between 1984 and 1989 15 children aged from 4 to 10 years were treated for a diaphyseal femoral fracture with an external fixation using a small Hofmann system. Fracture healing was without complications. Four children were able to walk on crutches non-weight-bearing after a short period. Six cases had complications, such as pin tract infection, inexplicable pain, or secondary displacement. One patient sustained a supracondylar fracture through one of the distal pin tracts. Hospital stay was longer than expected. In conclusion external fixation for femoral fractures in children is simple and elegant, but has considerable complications, while presumed advantages are not always obtained. In selected cases it is an attractive alternative, but the indications must be restricted. PMID- 1587564 TI - Undisplaced fractures of the distal third of the radius in children: an innocent fracture? AB - A series of 107 undisplaced or minimally displaced distal third radial fractures in children were assessed to try to identify the incidence and the factors associated with displacement. Of 27 fractures showing a volar (pronation) pattern, there were no cases of progression of the deformity. Of the 80 fractures showing a dorsal (supination) pattern, 22.5 per cent progressed. Of the unicortical fractures, 13.6 per cent showed a progression of the deformity compared with 47.6 per cent of the bicortical fractures. Of the unicortical fractures, 7.1 per cent of those showing a dorsal buckle displaced compared with 29.4 per cent of those with a cortical breach. PMID- 1587565 TI - Treatment of displaced subcapital femoral fractures with total hip replacement. AB - A series of 46 patients with 46 displaced subcapital femoral fractures were treated with total hip replacements. Indications for treatment were age between 65 and 79 years, a mental test score of greater than 7/13 and mobility sufficient to allow the patient to leave the house at least once a week. The main complication was dislocation (9 per cent), which tended to occur early, and was associated with inexperience of the surgeon. The 6-month mortality was 9 per cent. The mean Harris score of 33 patients reviewed at 3 years was 83. Preoperative mobility was well maintained and there was no evidence of deep sepsis or loosening. We recommend that this method of treatment should be studied further in a prospective comparative fashion. PMID- 1587566 TI - Prevention of bicycle accidents. AB - OBJECTIVE: To elucidate the way of reducing the number of bicycle accidents. A prospective study of all casualties from bicycle accidents attending an accident unit for a 29-month period was performed (1831 patients). A more detailed questionnaire on the causes of accidents was used for the last 12 months of the study (818 patients). RESULTS: In the 0-7 and 8-12 years age groups, 87.5 per cent and 66.2 per cent, respectively, were due to cyclist error. The 8-12-year old cyclists were twice as likely to have caused the accident if they had not had formal training (risk ratio = 2.0). Over the age of 18 years, 41.4 per cent were due to another road user. A motor vehicle was involved in 633 of the 1831 accidents. CONCLUSIONS: Children under the age of 8 years should not be allowed on public roads. Older children should only be allowed on the roads after formal training. This should become part of the school curriculum. A campaign to increase the awareness of motorists would be expected to reduce the number of cycle accidents. It would be beneficial to dedicate more roads and tracks to cycle use. Cyclists should be encouraged to wear more protective gear. PMID- 1587567 TI - Updating the accident and emergency record. AB - Eight records used in six accident and emergency (A/E) departments in the Mersey Region were reviewed. We studied (1) the structure of records; (2) the printed matter on the record; (3) the designated areas for documentation by the administrative, nursing and medical staff; and (4) the advantages of the records in transferring information to other departments and general practitioners. The use of computers in the departments was investigated. None of the hospitals used the same accident and emergency record. One of the records had a designated area for documenting the nursing care of the patients. None of the accident and emergency departments used computers for either delayed or real-time recording of patients' details. A computer-structured A/E Record will produce a legible, factual patient history, examination and care plan. The information recorded will be easily transferred to relevant hospital departments and ultimately to the community practitioners. PMID- 1587568 TI - Measured energy expenditure and plasma substrate and hormonal changes after severe head injury. AB - The influence of head trauma on the pattern of response to injury has been studied. Metabolic and hormonal data from brain injured patients over 20 days following injury were compared with an existing data base from non-head-injured patients and control subjects. The results demonstrated elevated concentrations of plasma glucose, lactate, non-esterified fatty acids (NEFA), cortisol, glucagon and insulin above that of control values in both groups after injury. Head injury as a separate factor did not affect the concentrations of any of these plasma substrates and hormones independently of its contribution to the Injury Severity Score (ISS). However, plasma catecholamine concentrations were higher in the head injured initially and at 7 days after injury. All head-injured patients showed an increase in metabolic rate (above predicted values) at some stage after injury. It should be noted, however, that there were some features of head injury (and its treatment) such as paralysis, ventilation and fasting which were not matched in the non-head-injured group. It was concluded that the metabolic changes occurring after head injury are similar to those occurring after extracranial injury and that therapeutic intervention has a major effect on the level of energy expenditure seen in these patients. PMID- 1587569 TI - Substrate oxidation and the contribution of protein oxidation to energy expenditure after severe head injury. AB - The 'flow' phase response to head injury is characterized by hypermetabolism and catabolism of lean body mass. In order to measure the contribution of protein oxidation (CPO) to resting metabolic expenditure (RME), 11 severely head injured patients (AIS 5) were studied. All patients had 24 h urine collections for at least 10 days after injury and RME was determined at intervals by indirect calorimetry. No patient received exogenous steroids. Peak urinary nitrogen excretion was 11.63 +/- 1.28 g/m2/day occurring between days 6 and 9 after injury. Fat oxidation was the greatest component of the RME at all times after head injury and the CPO to RME was 26.4 +/- 2.9 per cent during days 1-2, 31.8 +/ 3.3 per cent during days 3-5, 28.6 +/- 3.4 per cent during days 6-9 and 23.3 +/- 3.8 per cent during days 10-20 after injury. These figures are higher than those previously reported for burns, musculoskeletal injury or sepsis. The mechanism for the increased CPO is unclear. It may be related to such conditions of management as paralysis and fasting, but more likely it is an idiosyncratic feature of the metabolic response to head injury. PMID- 1587570 TI - Carpometacarpal dislocation: an aid to diagnosis. AB - Although the 'true' lateral radiograph of the hand has improved diagnosis of carpometacarpal dislocation, cases can still be missed if only the carpometacarpal joint area is inspected, as overlap of the adjoining joints can make interpretation difficult. Measurement of the angle between the long axis of the second and fifth metacarpal bones on a true lateral radiograph, in cases of fifth carpometacarpal dislocation is advocated, as the carpometacarpal angle is increased compared with controls (38.5 degrees compared with 9.8 degrees). A lesser increase in the carpometacarpal angle is suggestive of subluxation of this joint and this should be examined under anaesthesia. PMID- 1587571 TI - Stabilization of acute acromioclavicular dislocation by a modified Bosworth technique: a long-term follow-up study. AB - We reviewed 31 patients who underwent modified Bosworth procedures for grade III acromioclavicular dislocation. Their average age at the time of surgery was 32.5 years (range 18-60 years) and the mean follow-up was 11.6 years (range 5-20.6 years). The operation was performed for young, active individuals engaged in heavy manual work, in those who wished to return to contact sports and in patients with prominent clinical deformity. The results were analysed using the criteria suggested by Imatani et al. (1975). Of the patients, 24 (77 per cent) had excellent or good results and seven (23 per cent) had fair or poor results. There was no correlation between the radiological findings and the clinical results. PMID- 1587572 TI - A classification of acute acromioclavicular dislocation: a clinical, radiological and anatomical study. AB - Forty-eight patients with acute acromioclavicular dislocation were assessed clinically and radiologically before random allocation to non-operative management (28) or open reduction and coracoclavicular screw fixation (20) and followed for a minimum of 4 years. In 6 patients, late salvage surgery was required, the results of which were inferior to early operative intervention. Early surgery also gave better results than non-operative treatment in severe disruptions which could be identified in the acute stage. Three types of acromioclavicular dislocation which have predictable clinical outcomes could be distinguished on radiographs. When treated non-operatively, type A dislocations (19 per cent) may develop painful subluxation, type B (68 per cent) remain dislocated but retain sufficient muscle attachment to avoid fatigue on activity, and type C (12 per cent) leave a weak and unsightly shoulder. In type C dislocations, the clavicle is displaced 2 cm or more from the acromion on plain anteroposterior radiographs and the attached origin of the anterior deltoid is avulsed. Type C dislocations may benefit from early operative reconstruction. PMID- 1587573 TI - Fatal penetrating head injury during a game of soccer. PMID- 1587574 TI - Tarsal tunnel syndrome following an ankle fracture. PMID- 1587575 TI - Salter-Harris III fracture-dislocation of the proximal humeral epiphysis. PMID- 1587576 TI - Blunt tear of the middle colic artery without ensuing colonic infarction. PMID- 1587577 TI - Unusual cause of acute superficial posterior compartment syndrome. PMID- 1587578 TI - Late presentation of a ruptured iliac aneurysm to a trauma department. PMID- 1587579 TI - The true 'boxer's fracture'? PMID- 1587580 TI - Low-voltage electrothermal neck injury. PMID- 1587581 TI - Extensor tendon and ulnar styloid entrapment in Smith's fracture. PMID- 1587582 TI - Multiple adhesins of streptococci. PMID- 1587583 TI - Plasmid-encoded outer membrane protein YadA mediates specific binding of enteropathogenic yersiniae to various types of collagen. AB - The plasmid-encoded outer membrane protein YadA of enteropathogenic yersiniae is associated with pathogenicity. Recently, collagen binding of YadA-positive yersiniae was reported without detailed characterization (L. Emody, J. Heesemann, H. Wolf-Watz, M. Skurnik, G. Kapperud, P. O'Toole, and T. Wadstrom, J. Bacteriol. 171:6674-6679, 1989). To elucidate the nature of collagen binding to YadA, we used a recombinant Yersinia strain expressing the cloned YadA gene. Direct binding of YadA-positive yersiniae to collagens was demonstrated in affinity blot experiments on nitrocellulose filters. A spectrum of collagen types in a wide concentration range were tested for their ability to block binding of 125I labeled collagen type II to YadA-positive yersiniae. The results indicate a specific binding site(s) for YadA in collagen types I, II, III, IV, V, and XI. In contrast, collagen type VI did not bind to YadA. To characterize the binding site(s) more precisely, isolated collagen chains and cyanogen bromide fragments were investigated. These studies revealed that binding of YadA to collagen type I is confined to the alpha 1(I) chain, whereas the binding site within collagen type XI is localized in the alpha 3(XI) chain. alpha 2(I), alpha 1(XI), and alpha 2(XI) did not bind to YadA. Most interestingly, in the alpha 1(II) chain the specific binding site for YadA resides in the cyanogen bromide fragment CB10. The latter might indicate a binding site that does not depend on conformation. Based on these findings, further fragmentation and the synthesis of peptides may allow definition of the peptide sequence(s) relevant for YadA binding. PMID- 1587584 TI - Alterations in the superoxide dismutase gene of an isoniazid-resistant strain of Mycobacterium tuberculosis. AB - Genetic analysis of a set of six Mycobacterium tuberculosis strains differing in virulence for the guinea pig revealed an altered restriction enzyme fragmentation pattern associated with the superoxide dismutase (SOD) gene in a low-virulence, isoniazid-resistant strain. In addition, it was found that the SOD enzyme produced by the isoniazid-resistant strain differed in its electrophoretic mobility from the SOD of other M. tuberculosis strains. Detailed analysis of these strain-specific differences showed that the restriction fragment length polymorphism resulted from the presence of a copy of a repetitive element 552 bp upstream of the SOD gene and that the anomalous electrophoretic mobility arose from a single nucleotide change, resulting in replacement of an aspartic acid residue by histidine in the SOD enzyme of the isoniazid-resistant strain. Possible relationships between genetic changes and strain-dependent differences in virulence are discussed. PMID- 1587585 TI - Molecular characterization of an RTX toxin determinant from Actinobacillus suis. AB - RTX cytolysins are a family of calcium-dependent, pore-forming, secreted toxins found in a variety of gram-negative bacteria. The prototypical member of this family is the alpha-hemolysin of Escherichia coli. The RTX genetic determinants from seven members of the family Pasteurellaceae, Pasteurella haemolytica, Actinobacillus actinomycetemcomitans, and A. pleuropneumoniae serotypes 1,5,7, and 9 were previously cloned and sequenced. Using the leukotoxin determinant from P. haemolytica serotype A1 as a probe, we detected the presence of RTX-type determinants in Actinobacillus suis, A. equuli, and A. lignieresii of the family Pasteurellaceae. All three species elaborate proteins of approximately 104 to 110 kDa that are recognized by polyclonal antisera against the 104-kDa hemolysin of A. pleuropneumoniae serotype 1. An RTX determinant of A. suis isolate 3714 was cloned and sequenced and was found to be almost identical to the RTX determinant of A. pleuropneumoniae serotypes 5 and 9. In addition, the determinant is not composed of four contiguous genes, as had been reported for most other RTX determinants; instead, the genes encoding the two proteins responsible for secretion of the toxin are at a locus distinct from that containing the toxin structural and activation genes. PMID- 1587586 TI - Gene block encoding production of cytotoxic necrotizing factor 1 and hemolysin in Escherichia coli isolates from extraintestinal infections. AB - Cytotoxic necrotizing factors (CNFs) are Escherichia coli protein toxins causing cell multinucleation and enlargement in tissue cultures and necrosis in rabbit skin. In E. coli isolates causing urinary tract infections in humans, the production of CNF1 is closely associated with hemolysin production. In this study, we obtained data suggesting that this phenotypic association is due to the genetic linkage of the determinants of the two toxins on the chromosome of uropathogenic E. coli. The genes encoding hemolysin and CNF1 were shown to be closely linked in a 37-kb cloned DNA fragment from an E. coli urinary tract isolate of serotype O4:K12:H5 (E-B35). A DNA region encoding CNF1 production but not hemolysin production was further subcloned as a 12-kb SalI-EcoRI fragment and used as a CNF1-specific gene probe. DNA hybridization experiments indicated that the CNF1 and hemolysin determinants were closely linked on the chromosomes of isolate E-B35 and six additional extraintestinal isolates belonging to serogroups O2, O4, O6, O22, O75, and O85. PMID- 1587587 TI - Construction and analysis of a Vibrio cholerae delta-aminolevulinic acid auxotroph which confers protective immunity in a rabbit model. AB - Vibrio cholerae CVD101 is a very effective live vaccine. Although this strain does not produce active cholera toxin because of a mutation in the gene for the cholera toxin A subunit, it still shows residual pathogenicity. To attenuate CVD101 further, we set out to isolate derivatives of CVD101 which were limited in their ability to proliferate in vivo. Two delta-aminolevulinic acid auxotrophs of CVD101, designated V286 and V287, were isolated by transposon mutagenesis and penicillin enrichment. Southern blotting revealed that the mutants differed with respect to the location of the transposon insertion. Under aerobic conditions, in the absence of delta-aminolevulinic acid, both mutants showed diminished growth compared with CVD101. The growth of V286 was most severely affected. Microaerophilic growth of both mutants was less affected. Competition experiments with a rabbit model showed that strain V286 was found in numbers 10(3)- to 10(4) fold lower than its parental strain. This observation indicates that strain V286 is impaired in its ability to colonize the rabbit intestine. It also supports an important role for aerobic growth in the colonization of the intestine by V. cholerae. Vaccination of rabbits with a single dose of strain V286 resulted in full protection against challenge with a virulent strain. Strain V286 was not shed from rabbits in a cultivatable form. Our results suggest that delta aminolevulinic acid auxotrophy can attenuate V. cholerae by limiting its ability to colonize without affecting its capacity to induce protective immunity. Furthermore, this type of mutation may prevent the spread of V. cholerae vaccine strains in the environment. PMID- 1587588 TI - Tyrosine protein kinase inhibitors block invasin-promoted bacterial uptake by epithelial cells. AB - The ability to enter into (invade) mammalian cells is an essential virulence determinant of many pathogenic bacteria and intracellular parasites. These organisms are internalized by host cells upon attachment to their surface. However, the mechanisms used by intracellular parasites to induce internalization into host cells have not been defined. We found that the protein kinase inhibitor staurosporine blocks invasion by some pathogenic bacteria, including Yersinia enterocolitica and Yersinia pseudotuberculosis. Using Escherichia coli containing the cloned Y. enterocolitica invasion gene inv (which codes for invasin, an integrin-binding protein), we found that staurosporine inhibits invasion by blocking bacterial internalization. Two specific tyrosine protein kinase inhibitors, genistein and tyrphostin, also block the internalization but not the binding of bacteria, suggesting that bacterial uptake may be dependent on the activity of this enzyme class in host HeLa cells. In contrast to invasion promoted by invasin, the invasion of HeLa cells by Salmonella typhimurium is not inhibited by any of these drugs. PMID- 1587589 TI - Safety, immunogenicity, and efficacy in monkeys and humans of invasive Escherichia coli K-12 hybrid vaccine candidates expressing Shigella flexneri 2a somatic antigen. AB - A live, oral Shigella vaccine, constructed by transfer of the 140-MDa invasiveness plasmid from Shigella flexneri 5 and the chromosomal genes encoding the group- and type-specific O antigen of S. flexneri 2a to Escherichia coli K 12, was tested in humans. Designated EcSf2a-1, this vaccine produced adverse reactions (fever, diarrhea, or dysentery) in 4 (31%) of 13 subjects who ingested a single dose of 1.0 x 10(9) CFU, while at better-tolerated doses (5.0 x 10(6) to 5.0 x 10(7) CFU), it provided no significant protection against challenge with S. flexneri 2a. A further-attenuated aroD mutant derivative, EcSf2a-2, was then tested. Rhesus monkeys that received EcSf2a-2 in three oral doses of ca. 1.5 x 10(11) CFU experienced no increase in gastrointestinal symptoms compared with a control group that received an E. coli K-12 placebo. Compared with controls, the vaccinated monkeys were protected against shigellosis after challenge with S. flexneri 2a (60% efficacy; P = 0.001). In humans, EcSf2a-2 was well tolerated at inocula ranging from 5.0 x 10(6) to 2.1 x 10(9) CFU. However, after a single dose of 2.5 x 10(9) CFU, 4 (17%) of 23 subjects experienced adverse reactions, including fever (3 subjects) and diarrhea (209 ml) (1 subject), and after a single dose of 1.8 x 10(10) CFU, 2 of 4 subjects developed dysentery. Recipients of three doses of 1.2 to 2.5 x 10(9) CFU had significant rises in serum antibody to lipopolysaccharide (61%) and invasiveness plasmid antigens (44%) and in gut derived immunoglobulin A antibody-secreting cells specific for lipopolysaccharide (100%) and invasiveness plasmid antigens (60%). Despite its immunogenicity, the vaccine conferred only 36% protection against illness (fever, diarrhea, or dysentery) induced by experimental challenge (P = 0.17). These findings illustrate the use of an epithelial cell-invasive E. coli strain as a carrier for Shigella antigens. Future studies must explore dosing regimens that might optimize the protective effects of the vaccine while eliminating adverse clinical reactions. PMID- 1587590 TI - Cytoadherence and ultrastructure of Plasmodium falciparum-infected erythrocytes from a splenectomized patient. AB - In malarial infections of primates, the spleen has been shown to modulate parasite antigen expression on the surfaces of infected erythrocytes. The processes affected include cytoadherence, which is central to the pathophysiology of severe falciparum malaria, and the related phenomenon of rosette formation. In this study, the cytoadherence and rosette formation behaviors of Plasmodium falciparum-infected erythrocytes from a splenectomized patient were examined during the first erythrocytic cycle in vitro. Ultrastructural studies were also performed. Infected erythrocytes were found to cytoadhere to C32 melanoma cells via leukocyte differentiation antigen CD36 but not intercellular adhesion molecule 1. They also displayed on their surfaces electron-dense knobs similar in structure and density to those on infected erythrocytes from intact hosts. These findings may reflect a stable cytoadherent phenotype of the parasite isolate that is unaffected by the absence of the spleen. Alternatively, the modulating role of the spleen may have been assumed by other organs of the mononuclear phagocytic system in a previously infected individual. No rosette formation was observed, but as not all natural isolates form rosettes, this observation may or may not be related to the asplenic status of the patient. Parasite and host factors appear to be important in determining the effect of splenectomy on cytoadherence and rosette formation in human falciparum malaria. PMID- 1587591 TI - Novel invasion determinant of enteropathogenic Escherichia coli plasmid pLV501 encodes the ability to invade intestinal epithelial cells and HEp-2 cells. AB - An Escherichia coli K-12 transformant carrying 96.5-kb plasmid pLV501 from enteropathogenic E. coli (EPEC) strain K798 is able to produce the same characteristic attaching-effacing lesions in a rabbit ileal biopsy explant model as its parent strain. Cloned EcoRI-SalI DNA restriction fragments from this plasmid failed to reproduce the attaching-effacing lesions, but one recombinant plasmid, pLV527, containing 4.5 kb of pLV501 DNA, conferred on E. coli DH1 transformants the ability to invade enterocytes in the rabbit explant model. DH1(pLV527) was also able to adhere to and invade HEp-2 cells. The relative invasive ability of DH1(pLV527) was quantified by recovery of internalized bacteria following gentamicin treatment of infected HEp-2 monolayers. DH1(pLV527) was 1,000-fold more invasive than DH1 carrying pBR322 or a recombinant plasmid which had no physiological effect on ileal biopsy explants but was less invasive than an enteroinvasive E. coli strain or a transformant carrying the cloned invasion genes of Shigella flexneri. Invasion by DH1(pLV501) could also be detected but occurred at a level 30 times lower than that by DH1(pLV527). Colony hybridization of the pLV527 insert against a panel of 49 EPEC and related strains revealed that only 11 contained pLV527-hybridizing sequences; thus, the invasion determinant is not an essential component of the attachment-effacement pathogenic mechanism. One pLV527-hybridizing strain displayed both attachment-effacement and invasiveness in the rabbit ileal biopsy explant model. No significant hybridization was observed to non-EPEC invasive pathogenic enteric bacteria, indicating that the invasion determinant encoded on pLV527 is distinct from those used by these organisms. PMID- 1587592 TI - Properties of pertussis toxin B oligomer assembled in vitro from recombinant polypeptides produced by Escherichia coli. AB - The subunits that make up the pentameric B oligomer of pertussis toxin (S2, S3, S4, and S5) were individually synthesized as recombinant polypeptides in Escherichia coli, isolated as insoluble inclusion bodies, and assembled into a multimeric form in vitro by spontaneous association following treatment with a chaotropic agent, reduction, and reoxidation. The recombinant B multimer, purified by fetuin-Sepharose affinity chromatography, contained all four of the individual subunits and possessed the mitogenic and hemagglutinating activities characteristic of the native B oligomer. Immunization of mice with the recombinant B oligomer elicited antibodies that neutralized pertussis toxin in vitro and, moreover, provided protection in vivo against the leukocytosis promoting activity of the toxin. These results demonstrate the potential for assembly of complex multimeric proteins from recombinant DNA-derived polypeptides and provide a novel means for production of an acellular pertussis vaccine component. PMID- 1587593 TI - Proteinases of Proteus spp.: purification, properties, and detection in urine of infected patients. AB - The proteinases secreted by pathogenic strains of Proteus mirabilis, P. vulgaris biotype 2, P. vulgaris biotype 3, and P. penneri were purified with almost 100% recovery by affinity chromatography on phenyl-Sepharose followed by anion exchange chromatography. The proteinase purified from the urinary tract pathogen P. mirabilis, which we had previously shown to degrade immunoglobulins A and G, appeared as a composite of a single band and a double band (53 and 50 kDa, respectively) on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The other Proteus proteinases had similar patterns but slightly different mobilities. In each case all proteinase activity in culture supernatants was demonstrated by gelatin-sodium dodecyl sulfate-polyacrylamide gel electrophoresis to be associated with only the triple-band complex; all three bands were proteolytically active. The P. mirabilis proteinase was resistant to inhibitors of both serine and thiol proteinases but strongly inhibited by metal chelators, although it was not affected by phosphoramidon, an inhibitor of the thermolysin group of bacterial metalloproteinases. Active proteinase was detected in urine samples from P. mirabilis-infected patients; this is consistent with our detection of immunoglobulin A fragments of a size suggestive of P. mirabilis proteinase activity. PMID- 1587594 TI - Isolation of two Giardia lamblia (WB strain) clones with distinct surface protein and antigenic profiles and differing infectivity and virulence. AB - To determine the relationship between antigenic profiles and pathogenicity among Giardia lamblia clones (WB strain), trophozoites were cloned by the technique of limiting dilution. The phenotype of each clone was determined by an indirect immunofluorescence test using a polyclonal rabbit anti-G. lamblia trophozoite serum made against the parent strain. Two clones were chosen for further studies: a highly fluorescent clone, F+, in which more than 95% of the trophozoites fluoresced, and a low-fluorescence clone, F-, in which fewer than 5% fluoresced. Sodium dodecyl sulfate-polyacrylamide gradient gel electrophoresis and enzyme linked immunotransfer blot studies of the membrane fractions of the two clones and parent strain revealed differences in both the total protein and antigenic profiles. A serum cytotoxicity test with the polyclonal serum showed that the F+ clones were more susceptible to immobilization and killing, while the majority of cells of the F- clones were resistant to such killing. Assessment of the infectivity of the two clones in the Mongolian gerbil animal model indicated that the F- clone more readily initiated infections, produced more cysts, had a higher intestinal trophozoite load, and produced a more severe clinical syndrome, while the F+ clone was less phenotypically stable in vivo and in some cases took longer to be cleared from the intestine. PMID- 1587595 TI - Intracellular growth of Afipia felis, a putative etiologic agent of cat scratch disease. AB - The organism Afipia felis, which is though to be an etiologic agent of cat scratch disease, is a gram-negative rod that is clearly seen in infected tissue but is very difficult to isolate from clinical specimens; there has been only one report to date of the successful isolation and maintenance of the bacterium on artificial medium. We have found that A. felis will attach, invade via phagocytosis, and multiply intracellularly within the phagosomes of primary human monocytes and HeLa cells. Once in the cell, the bacterium appears to change morphologically, becoming longer and more pleomorphic, and loses its ability to grow on an artificial medium. Unique proteins have been identified in both the intra- and extracellular variants of A. felis. Convalescent-phase sera from patients with cat scratch disease react poorly with intracellular and extracellular bacteria, suggesting a poor humoral response. The tissue culture protocol presented has been used to isolate 14 new strains of A. felis and has for the first time permitted study of the pathogenesis of this unique organism. PMID- 1587596 TI - Effect of donor and recipient immunization protocols on primary and secondary human antibody responses in SCID mice reconstituted with human peripheral blood mononuclear cells. AB - We have examined the ability of mice with severe combined immunodeficiency (SCID mice) reconstituted with human peripheral blood mononuclear cells (PBMC) to generate human antibody responses after specific immunization. SCID mice reconstituted with cells from a keyhole limpet hemocyanin (KLH)-naive donor are unable to generate specific human antibody responses after immunization with that antigen. After KLH immunization, SCID mouse recipients of human PBMC from a KLH immune subject develop specific human antibody levels exceeding those of the donor. Human antitetanus antibody titers in reconstituted, immunized mice are also equivalent to those of the donor, provided that the mice are immunized within days of human cell transplantation. The ability of reconstituted mice to generate high titers of specific human antibody is lost within 35 days of human cell reconstitution, even though titers of total human immunoglobulin (Ig) are preserved. SCID mice reconstituted with tetanus-immune donor cells fail to generate IgA responses after booster immunization, and IgM responses are low or nonexistent. These data indicate that early exposure of the adoptive recipients of human cells to antigen is required to transfer specific human humoral responses. These findings are also consistent with a requirement for persistence of antigen for the maintenance of B-cell memory. The ability to achieve specific human antibody levels equivalent to those obtained with humans indicates that reconstituted mice may be useful for the evaluation of human antibody-mediated mechanisms of resistance to infection. The data indicate, however, that cells from immunized donors will have to be used for such studies. PMID- 1587597 TI - Cryptosporidium parvum in calves: kinetics and immunoblot analysis of specific serum and local antibody responses (immunoglobulin A [IgA], IgG, and IgM) after natural and experimental infections. AB - Fecal and serum anti-Cryptosporidium parvum immunoglobulin A (IgA), IgM, and IgG were monitored by an enzyme-linked immunosorbent assay after experimental and natural infection of calves with C. parvum. Although all experimentally infected calves showed high levels of colostral antibodies in the feces, they acquired C. parvum infection. Three of five animals died. Calves which acquired natural infection showed only diarrhea. Levels of colostral coproantibodies dropped quickly. Experimental infection was followed by a rise in local anti-C. parvum IgM levels from day 5 postinfection (p.i.). IgM peaked at day 14 p.i. and then disappeared quickly. Anti-C. parvum IgA levels rose between days 7 and 14 p.i. and decreased slowly. Rising levels of coproantibodies coincided with falling oocyst output. Fecal anti-C. parvum IgG levels rose slightly during oocyst output, and IgG disappeared 3 weeks p.i. Similar kinetics were established in naturally infected calves. Although fecal anti-C. parvum IgA levels declined slowly, reinfections were established 5, 7, and 14 weeks after the primary contact. Serum anti-C. parvum IgG levels rose during maximal oocyst excretion, whereas serum anti-C. parvum IgA levels peaked later than did local IgA levels. Challenge reinfection of naturally infected calves at day 112 was not followed by clinical signs or oocyst output or by a secondary antibody response. Sequential Western immunoblotting with fecal extracts revealed up to 32 different parasite antigens. Convalescent-phase sera recognized up to 23 antigens. Fecal IgA reacted intensely with antigens with relative molecular weights (M(r)) of approximately 11,000 and 15,000. These antigens were not recognized by convalescent-phase serum IgG. Both local IgA and serum IgG also showed strong reactions with 23,000- and 44,000-M(r) antigens and with several antigens of between 66,200 and 200,000 M(r). Most bands remained detectable for at least 16 weeks p.i. PMID- 1587598 TI - Structure and function of a 40,000-molecular-weight protein antigen of Mycobacterium tuberculosis. AB - A gene encoding a protein antigen from Mycobacterium tuberculosis with a molecular weight of 40,000 has been sequenced. On the basis of sequence homology and functional analyses, we demonstrated that the protein is an L-alanine dehydrogenase (EC 1.4.1.1). The enzyme was demonstrated in M. tuberculosis and Mycobacterium marinum but not in Mycobacterium bovis BCG. The enzyme may play a role in cell wall synthesis because L-alanine is an important constituent of the peptidoglycan layer. Although no consensus signal sequence was identified, we found evidence which suggests that the enzyme is secreted across the cell membrane. The enzyme was characterized and purified by chromatography, thus enabling further studies of its role in virulence and interaction with the immune system of M. tuberculosis-infected individuals. PMID- 1587599 TI - Experimental epididymitis due to Chlamydia trachomatis in rats. AB - A new animal model of epididymitis due to Chlamydia trachomatis was developed. Adult male Wistar rats were inoculated in the vas deferens with C. trachomatis biovar mouse pneumonitis. After infection, C. trachomatis was recovered from the epididymides for up to 90 days. At day 30, organisms were also reisolated from the testes. Clinical findings included enlargement of infected epididymides and concurrent atrophy of the ipsilateral testes. Histological lesions in the epididymides consisted of pyogranulomatous inflammation, abscesses, and spermatic granulomas. Infection of the testis by C. trachomatis was associated with pyogranulomatous changes. In addition, testicular degeneration, characterized by moderate to severe loss of the germinal epithelium, was noted. Chlamydial antigen was detected within epithelial cells, intratubular macrophages, and macrophages in the stroma of the epididymis by immunoperoxidase staining. This rat model of chlamydial epididymitis appears to clinically and histopathologically mimic the human disease. This model offers the opportunity for further studies on the pathogenesis and sequelae of chlamydial epididymitis. PMID- 1587600 TI - Immune responses of systemic and mucosal lymphoid organs to Pnu-Imune vaccine as a function of age and the efficacy of monophosphoryl lipid A as an adjuvant. AB - A murine model system was established to study immune responses to the Pnu-Imune vaccine, which is made up of 23 different pneumococcal capsular polysaccharides. In this animal model, antibody-forming cell responses to 21 of 23 individual polysaccharides in the vaccine were detected. The Pnu-Imune vaccine elicited good antibody responses from the spleens and mesenteric lymph nodes (MLN) of young mice, whereas a variety of other peripheral lymph nodes were unresponsive. The immunoglobulin M plaque-forming cell (PFC) response in the spleen to the Pnu Imune vaccine (given intraperitoneally or subcutaneously) decreased dramatically with increasing age. However, the spleen and MLN differed in their susceptibility to an age-associated decline in immune function. While the PFC responses in the spleen declined with age, the PFC response in the mucosa-associated MLN did not decline with age but instead remained constant over the entire age span of 4 to 28 months studied. These studies showed that the spleen, peripheral lymph nodes, and MLN did not demonstrate parallel age-associated defects in antibody responses to pneumococcal polysaccharides when the antigen was administered systematically. Also, the deficient splenic antibody response to Pnu-Imune vaccine in aged mice could be enhanced by injecting a combination of Pnu-Imune vaccine and the nontoxic adjuvant monophosphoryl lipid A. Moreover, an immunoglobulin G response was induced when the immunogen was a mixture of vaccine and adjuvant. PMID- 1587601 TI - Identification and initial characterization of five Cryptosporidium parvum sporozoite antigen genes. AB - Cryptosporidium parvum, an Apicomplexan parasite of gastrointestinal epithelial cells, causes severe disease in persons with AIDS and is a common cause of self limited diarrhea in children, animal handlers, and residents of developing countries. No approved therapy exists; in research studies, however, hyperimmune bovine colostrum raised to Cryptosporidium oocysts and sporozoites has eradicated disease or decreased parasite burden in some AIDS patients. Although the protective antigens recognized by bovine hyperimmune colostrum have not been defined, protective antigens of other Apicomplexan parasites frequently have been associated with two unique structures of invasive forms, the trilaminar pellicle and the apical complex. In order to identify immunogenic Cryptosporidium proteins that may be protective antigens for use as recombinant immunogens in passive and/or active immunotherapy, we screened two genomic DNA expression libraries with polyspecific anti-Cryptosporidium antibodies. We used an approach to cloning apical complex and pellicle protein antigens that succeeded despite the lack of large numbers of organisms that would be necessitated for conventional biochemical approaches requiring organelle or membrane purification. We report here the molecular cloning of five C. parvum genes and the characterization of the cognate sporozoite proteins having molecular masses of greater than 500, 68/95, 45, 23, and 15/35 kDa. The light microscopic immunofluorescence pattern of antibodies recognizing these protein antigens suggest that they are located in the pellicle or apical complex of Cryptosporidium sporozoites. PMID- 1587602 TI - Cloning and nucleotide sequence of the gene encoding the 136-kilodalton surface protein (muramidase-released protein) of Streptococcus suis type 2. AB - We cloned and sequenced the gene encoding the muramidase-released protein (MRP) of a pathogenic Streptococcus suis type 2 strain to determine whether its amino acid sequence resembles that of proteins with known functions and to determine its function in virulence. The complete nucleotide sequence composing the gene and the regions flanking it was determined. The deduced amino acid sequence revealed the presence of a signal peptide at the N terminus and a cell envelope anchor at the C terminus, both of which resembled similar regions in several other surface proteins from gram-positive bacteria. The processed form of MRP has a length of 1,209 amino acids and a calculated molecular weight of 131,094. A highly repetitive region preceded the envelope anchor. The repeated units were preceded by a proline-rich stretch of amino acids (26 of 86). No overall homologies were observed between the amino acid sequence of MRP and protein sequences in the EMBL data bank. A particular region within the amino acid sequence, however, showed some similarity with the fibronectin-binding protein of Staphylococcus aureus. Binding of MRP to human fibronectin, however, could not be confirmed. PMID- 1587604 TI - Mouse intravaginal infection with Trichomonas vaginalis and role of Lactobacillus acidophilus in sustaining infection. AB - Recent work with a mouse model of Trichomonas vaginalis infection indicated that only 25% of mice harbor Lactobacillus spp. and that T. vaginalis infection rates fall rapidly after 7 days postinfection. In women infected with T. vaginalis, there is a disruption of the Lactobacillus population, which usually predominates. In an attempt to establish a better mouse intravaginal infection that resembles human disease, we established Lactobacillus acidophilus in estrogenized BALB/c mice. T. vaginalis was then inoculated intravaginally into mice previously infected with L. acidophilus and into mice in an untreated group. From 52 mice, 50-microliters vaginal washes were collected, cultured, and examined daily for live trichomonads after inoculation. Although initial infectivity in the two groups was comparable (79 to 83%), L. acidophilus-infected mice showed greater duration of infection. At day 24 postinfection, 69% of L. acidophilus-infected mice were still infected with T. vaginalis compared with only 11% of untreated mice (P = 0.002). The addition of L. acidophilus did not significantly alter the resident mouse vaginal flora. By the addition of L. acidophilus, the mouse will be valuable for studying factors involved in T. vaginalis infectivity and pathogenicity. PMID- 1587603 TI - Staphylococcus aureus susceptibility to thrombin-induced platelet microbicidal protein is independent of platelet adherence and aggregation in vitro. AB - Bacterium-platelet interactions at the cardiac valve surface represent an important initial step in the induction of infective endocarditis (IE). This cell cell interaction may play either a protagonistic role in the induction of IE via bacterial adherence to and aggregation of platelets or an antagonistic role via secretion of platelet-derived microbicidal molecules. We examined the spectrum and interrelationship of three aspects of the interaction of 20 clinical Staphylococcus aureus isolates with rabbit platelets in vitro: (i) S. aureus adherence to platelets; (ii) S. aureus-induced platelet aggregation; and (iii) S. aureus resistance to the action of thrombin-induced platelet microbicidal protein (PMP; low-molecular-weight cationic peptides contained in alpha granules). Among the 20 S. aureus isolates (11 bacteremia, 9 endocarditis), there was a heterogeneous distribution profile for each of the bacterium-platelet interaction parameters studied. For S. aureus-platelet adherence and S. aureus-induced platelet aggregation, 3 of 20 and 7 of 20 isolates tested were considered highly active for each respective parameter; 5 of 20 staphylococcal strains were deemed resistant to the bactericidal action of PMP. In addition, more endocarditis isolates (45%) were PMP resistant than strains from patients without endocarditis (19%). When analyzed concomitantly, there was a significant, positive correlation between S. aureus-platelet adherence and S. aureus-induced platelet aggregation among isolates (P = 0.003; r = 0.78). In contrast, there were no statistically significant relationships between either platelet adherence or aggregation and PMP resistance among these 20 S. aureus isolates. These data suggest that platelet adherence and aggregation are related abilities of S. aureus, while resistance to thrombin-induced PMP is an independent phenotypic characteristic and potential virulence factor. PMID- 1587605 TI - Comparative roles of the Arg-Gly-Asp sequence present in the Bordetella pertussis adhesins pertactin and filamentous hemagglutinin. AB - Pertactin and filamentous hemagglutinin (FHA), proteins present on the surface of the gram-negative organism Bordetella pertussis, have been shown to contain the putative cell-binding sequence arginine-glycine-aspartic acid (RGD) and to promote eukaryotic cell attachment. The attachment of epithelial cells to purified pertactin and the entry of B. pertussis into human HeLa cells are both inhibited by an RGD-containing peptide derived from the pertactin sequence. In contrast, an RGD-containing peptide derived from the FHA sequence has no effect on either the attachment of epithelial cells to purified FHA or the entry of B. pertussis into HeLa cells. Staphylococcus aureus organisms coated with pertactin or FHA, purified from B. pertussis, enter HeLa cells more efficiently than S. aureus cells coated with bovine serum albumin. The pertactin-enhanced entry of S. aureus is inhibited by 75% in the presence of the RGD peptide from pertactin, whereas the RGD peptide derived from FHA has no effect on the increased entry promoted by the pertactin-coated or by the FHA-coated S. aureus. These results indicate that the active uptake of B. pertussis by certain mammalian cells may be mediated by the interaction of the RGD site found in pertactin with eukaryotic cell surface receptors. PMID- 1587606 TI - Common antigenic domains in transferrin-binding protein 2 of Neisseria meningitidis, Neisseria gonorrhoeae, and Haemophilus influenzae type b. AB - There is now considerable evidence to show that in the Neisseria and Haemophilus species, membrane receptors specific for either transferrin or lactoferrin are involved in the acquisition of iron from these glycoproteins. In Neisseria meningitidis, the transferrin receptor appears to consist of two proteins, one of which (TBP 1) has an M(r) of 95,000 and the other of which (TBP 2) has an M(r) ranging from 68,000 to 85,000, depending on the strain; TBP 2 binds transferrin after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electroblotting, but TBP 1 does not do so. The relative contributions of these two proteins to the binding reaction observed with intact cells and to iron uptake are presently unknown. However, they are being considered as potential components of a group B meningococcal vaccine. Analogous higher- and lower molecular-weight proteins associated with transferrin binding have been found in N. gonorrhoeae and Haemophilus influenzae. Previous work with polyclonal antibodies raised in mice with whole cells of iron-restricted N. meningitidis showed that the meningococcal TBP 2 exhibits considerable antigenic heterogeneity. Here, we report that antiserum against purified TBP 2 from one strain of N. meningitidis cross-reacts on immunoblotting with the TBP 2 of all meningococcal isolates examined, as well as with the TBP 2 of N. gonorrhoeae. This antiserum also cross-reacted with the TBP 2 of several strains of H. influenzae type b, thus showing the presence of common antigenic domains among these functionally equivalent proteins in different pathogens; no cross-reaction was detected with a purified sample of the human transferrin receptor. PMID- 1587607 TI - Protection of Aotus monkeys from malaria infection by immunization with recombinant hybrid proteins. AB - On the basis of investigations of the malarial blood-stage antigens SERP, HRPII, and MSAI from Plasmodium falciparum, we chose two Escherichia coli-expressed hybrid proteins containing selected partial sequences of these antigens. Antibodies raised against both hybrid proteins in rabbits and Aotus monkeys recognize the corresponding P. falciparum polypeptides. In two independent trials with 13 animals, immunization of Aotus monkeys with either of the two hybrid proteins administered in a well-tolerated oil-based formulation protected the animals from an experimental P. falciparum infection. PMID- 1587608 TI - Molecular cloning of epithelial cell invasion determinants from enterotoxigenic Escherichia coli. AB - Although penetration of the epithelial mucosa has not been identified as a virulence mechanism in enterotoxigenic Escherichia coli (ETEC), we have found that this pathogen is capable of invading human intestinal cell lines. Classical ETEC strain H10407 was most invasive for epithelial cell lines derived from ileocecal and colonic tissues. An ETEC cosmid library was screened for clones that could direct E. coli HB101 to invade cultured human ileocecal epithelial cells (HCT 8 cells). Three invasive recombinant cosmid clones were isolated. These cosmids could direct HB101 invasion at an efficiency that was equal to or greater than that of the parent ETEC strain. The invasion cosmids also allowed for enhanced HCT 8 cell adherence by HB101. Electron micrographs of ETEC and recombinant HB101 strains revealed intracellular bacteria contained within endocytic vacuoles. Restriction endonuclease mapping and hybridization analyses showed that the three ETEC clones represent two separate invasion systems present in the parent ETEC strain and that both systems are chromosomally encoded. The parent ETEC strain and one cloned invasion system did not invade HeLa cells. Interestingly, one cloned invasion system was capable of directing HB101 to invade HeLa cells. Invasion of HCT 8 cells by recombinant HB101 strains and the parent ETEC strain was inhibited by cytochalasin D, indicating that the wild-type and both cloned invasion systems trigger an actin polymerization-dependent uptake process. It is not known whether the invasive phenotype of ETEC is relevant for enterotoxigenic disease. However, the parent ETEC strain, as well as recombinant HB101 strains, was capable of transcytosis through polarized HCT 8 monolayers. This transcytosis suggests that ETEC may cross the gut epithelium in vivo and that this invasion may have a previously unrecognized role in the disease process. PMID- 1587609 TI - Cloning and characterization of transcripts showing virulence-related gene expression in Naegleria fowleri. AB - The pathogenic LEE strain of Naegleria fowleri isolated from human or mouse brain loses pathogenicity when cultured axenically in a nutrient broth. To identify genes differentially expressed in highly virulent versus weakly virulent amoebae, a cDNA library was constructed by using mRNA from amoebae recovered from a mouse brain. Two cDNA clones were isolated by differential screening of the library. The transcript homologous to clone Nf314 was preferentially expressed in highly virulent cells, whereas the transcript homologous to clone Nf435 was preferentially expressed in weakly virulent cells. Other clones showed negligible differential hybridization, but actin transcript levels were slightly elevated in the highly virulent cells. The Nf314 cDNA has an open reading frame for a 53-kDa protein 94% similar and 19% identical over 194 amino acid residues to serine carboxypeptidase from yeast cells, barley, and wheat. Southern blot analysis is consistent with a single copy of the Nf314 gene in the genome. Interestingly, the increased Nf314 transcript levels were present in cells fed on mouse brain, liver, or NIH 3T3 fibroblasts but not in cells fed on bacteria or in axenic culture. Thus, the inducer of the increased gene expression correlates with use of mammalian cells as a food source without regard to level of virulence. Since amoebae fed in culture on dissociated mouse brain were weakly virulent, as measured by their abilities to kill mice, the Nf314 gene may be required but is not sufficient for increased virulence. PMID- 1587610 TI - Protective effects of a leukotriene inhibitor and a leukotriene antagonist on endotoxin-induced mortality in carrageenan-pretreated mice. AB - The leukotrienes and tumor necrosis factor (TNF) play an important role in the pathophysiology of septic shock, in which hypotension, leukopenia, thrombocytopenia, and hemoconcentration are observed. This study was performed to examine the effects of a 5-lipoxygenase inhibitor (AA-861), a selective leukotriene receptor antagonist (ONO-1078), and a cyclooxygenase inhibitor (indomethacin) on endotoxin-induced mortality and TNF production in mice. Mice were injected intraperitoneally with carrageenan (5 mg per mouse), which we previously reported as an effective priming agent for lipopolysaccharide (LPS) induced TNF production and mortality (M. Ogata, S. Yoshida, M. Kamochi, A. Shigematsu, and Y. Mizuguchi, Infect. Immun. 59:679-683, 1991). The indicated doses of AA-861, ONO-1078, indomethacin, or controls were administrated subcutaneously 30 min before LPS (50 micrograms per mouse) provocation. The mortality of mice was significantly decreased by pretreatment with AA-861 (P less than 0.001) or ONO-1078 (P less than 0.01) but not by pretreatment with indomethacin. The 50% lethal dose of LPS in the mice treated with dimethyl sulfoxide or ethanol was 32 or 33 micrograms, respectively, and it increased to 83 micrograms with AA-861 or 59 micrograms with ONO-1078, respectively. Neither AA-861 nor ONO-1078 suppressed LPS-induced TNF production in sera. Treatment with AA-861 significantly decreased the leukopenia and thrombocytopenia, and ONO-1078 significantly decreased the hemoconcentration and thrombocytopenia. The role of endogenous TNF was also examined in the carrageenan-pretreated mice. Treatment with 2 x 10(5) U of rabbit anti TNF-alpha antibody intravenously 2 h before LPS challenge significantly suppressed the LPS-induced TNF activity and decreased the mortality. Therefore, both leukotrienes and TNF play important roles in endotoxin induced shock and mortality. PMID- 1587611 TI - Adjuvant effects of liposomes containing lipid A: enhancement of liposomal antigen presentation and recruitment of macrophages. AB - Liposomes containing lipid A induced potent humoral immune responses in mice against an encapsulated malaria antigen (R32NS1) containing NANP epitopes. The immune response was not enhanced by lipid A alone or by empty liposomes containing lipid A. Experiments to investigate the adjuvant mechanisms of liposomes and lipid A revealed that liposome-encapsulated R32NS1 was actively presented by bone marrow-derived macrophages to NANP-specific cloned T cells. The degree of presentation was related to the amount of liposomal antigen added per macrophage in the culture medium. At high cell densities, poor presentation occurred when liposomes lacked lipid A but excellent presentation occurred when the liposomes contained lipid A. Liposomes containing lipid A and encapsulated antigen also activated gamma interferon-treated macrophages to produce nitric oxide. Macrophage activation and antigen presentation occurred with liposomes that could not be detected by the Limulus amebocyte lysis assay. Intraperitoneal injection of liposomal lipid A caused a marked increase in the recruitment of immature (peroxidase-positive) macrophages to the peritoneum. On the basis of these experiments, we propose that the mechanism of the adjuvant action of liposomal lipid A is partly due to increased antigen presentation by macrophages and partly due to recruitment of an increased number of macrophages serving as antigen-presenting cells. PMID- 1587612 TI - Contribution of the pAD1-encoded cytolysin to the severity of experimental Enterococcus faecalis endophthalmitis. AB - The contribution of the pAD1-encoded cytolysin to Enterococcus faecalis virulence in an experimental endophthalmitis model was studied by using isogenic strains differing only in the location of transposon Tn917. The course of experimental endophthalmitis in New Zealand White rabbits was evaluated by postoperative reduction in retinal neuroresponsiveness, thin-section histopathology, and transmission electron microscopy. Infections caused by cytolytic E. faecalis resulted in 99% loss of retinal function at postoperative day 3, while isogenic, noncytolytic strains produced reductions of only 74.2%. Light microscopy revealed near-total destruction of retinal architecture at 24 h postinfection with cytolytic E. faecalis, while noncytolytic strains produced few or no destructive changes. Transmission electron microscopy revealed tissue destruction in retinal layers as early as 6 h postinfection with cytolytic E. faecalis. In vivo and in vitro growth rates of cytolytic and noncytolytic E. faecalis showed similar kinetics. These data demonstrate the contribution of the pAD1-encoded cytolysin to both the course and the severity of experimental E. faecalis endophthalmitis. PMID- 1587613 TI - Human immunodeficiency virus type 1 enhances intracellular growth of Mycobacterium avium in human macrophages. AB - Disseminated Mycobacterium avium infections are common in patients with AIDS and result in a reduced life expectancy. Human monocytes/macrophages are important target cells for both human immunodeficiency virus (HIV) and M. avium. We have studied the interaction in vitro of M. avium and HIV type 1 (HIV-1) in human macrophages. Human monocytes isolated from the peripheral blood of healthy individuals were infected with HIV-1, M. avium, or both. The intracellular growth of M. avium and the replication of HIV-1 were monitored for up to 5 weeks. Intracellular mycobacterial growth was seen in all M. avium infected cell cultures and was paralleled by increased production of interleukin 1 alpha and beta. Preinfection of the macrophages with HIV-1 reduced the interleukin 1 production and accelerated the intracellular growth of M. avium. These findings may explain in part the impaired control of mycobacterial infections seen with patients with AIDS. PMID- 1587615 TI - Preliminary characterization of Pseudomonas aeruginosa peptide chemotactins for polymorphonuclear leukocytes. AB - In a previous report, we showed that supernatants of Pseudomonas aeruginosa cultures exhibit chemotactic activity for polymorphonuclear leukocytes (PMNL). In this study, P. aeruginosa chemotactins were isolated, purified, and partially characterized. The organisms were cultured in Vogel-Bonner defined medium, and cultures were stopped in late log phase. Chemotactins withstood heating, remained unaltered after acid or alkali treatment in a pH range from 4 to 10, and resisted digestion by trypsin or carboxypeptidase, but chemotactic activity was decreased by 73% after incubation with pronase. Only 2% of the total chemotactic activity of culture supernatants could be extracted with chloroform. Chemotactins with molecular sizes less than 3 kDa constituted the largest contribution to the chemotactic activity of culture supernatants. Pretreatment of PMNL with 10(-5) M formylmethionyl-leucyl-phenylalanine (FMLP) inhibited chemotaxis towards FMLP and P. aeruginosa culture supernatants but not towards complement component C5a. In conclusion, the total chemotactic activity for PMNL of P. aeruginosa culture supernatants was due, almost exclusively, to chemotactins that have properties similar, if not identical, to those exhibited by formylmethionyl peptides. PMID- 1587614 TI - Antigens of Brucella abortus S19 immunodominant for bovine lymphocytes as identified by one- and two-dimensional cellular immunoblotting. AB - Cellular immune responses are influential for protection against intracellular bacteria such as brucellae. Therefore, identification of Brucella abortus antigens that activate primed bovine lymphocytes is fundamental for discerning the breadth of cellular response in bovine brucellosis. Potentially antigenic components of B. abortus S19 were isolated by sodium dodecyl sulfate polyacrylamide gel electrophoresis followed by nitrocellulose blotting. Specific one-dimensional blot segments induced proliferation of peripheral blood lymphocytes from all 25 of the vaccinated cattle tested and were defined as immunodominant. Individual proteins that stimulated lymphocyte proliferation were further characterized by two-dimensional cellular immunoblotting by two different approaches. Individual one-dimensional stimulatory blot segments were eluted, concentrated, and then subjected to two-dimensional cellular immunoblotting. Alternatively, entire two-dimensional gels containing all of the B. abortus components were blotted and nitrocellulose sections containing individual proteins were assayed for lymphocyte activation. Thirty-eight Brucella proteins that induced lymphocyte proliferation were resolved by both procedures. Phenotypic analysis of the proliferating cell population demonstrated the presence of CD4+, CD8+, and immunoglobulin M+ lymphocytes. Two immunogenic proteins, 12 and 31 kDa, identified by two-dimensional cellular immunoblotting, were subjected to partial N-terminal amino acid analysis. The 12-kDa protein was within the area of greatest lymphocyte proliferation, while the 31-kDa protein was chosen for comparison with a 31-kDa protein previously reported by others. A search of the National Biomedical Research Foundation protein data bank showed that the sequences were not homologous with other known proteins. Identification of Brucella proteins immunogenic for bovine lymphocytes provides an important step in distinguishing the various proteins involved in pathogenicity and/or disease resistance. PMID- 1587616 TI - The glycerolipid receptor for Helicobacter pylori (and exoenzyme S) is phosphatidylethanolamine. AB - We have previously shown that Helicobacter pylori specifically binds to a glycerolipid species preferentially found in the antrum of the human stomach. We now show by high-pressure liquid chromatographic analysis that this species is a form of phosphatidylethanolamine and that H. pylori specifically binds to bona fide phosphatidylethanolamine as detected by a thin-layer chromatogram overlay procedure. Considerable variation in the binding of H. pylori to phosphatidylethanolamine from different sources was observed, however, suggesting the importance of the nature of the long-chain hydrophobic moiety. A similar binding specificity was shown by exoenzyme S from Pseudomonas aeruginosa, consistent with our hypothesis that that an exoenzyme S-like adhesin is responsible for the binding of H. pylori to its lipid receptors. PMID- 1587617 TI - Invasion by Salmonella typhimurium is affected by the direction of flagellar rotation. AB - When grown aerobically, Salmonella typhimurium exhibits a low level of entry into tissue culture cells. We have isolated an S. typhimurium Tn10 mutant which, when grown under aerobic conditions, efficiently invades HEp-2 cells. Sequencing of S. typhimurium DNA adjacent to the site of the Tn10 element showed that the insertion disrupted transcription of the aspartate receptor gene, tar. Polar effects of the transposon on downstream genes also eliminated chemotaxis. Isogenic nonchemotactic (Che-), as well as nonmotile (Mot-) and nonflagellated (Fla-), S. typhimurium strains were examined for their ability to invade HEp-2 cells. "Smooth" swimming Che- mutants (cheA, cheW, cheR, and cheY) were found to possess increased invasiveness for cultured mammalian cells. In contrast, a "tumbly" cheB mutant and Mot- (flagellated) strain were found to have decreased levels of tissue culture invasiveness. A Fla- strain was found to be as invasive as the wild-type strain if centrifugation was used to facilitate contact with the monolayer surface. In addition, the observed hyperinvasiveness of the smooth swimming tar::Tn10 mutant was suppressed when the strain was paralyzed by the introduction of a mot or fla mutation. A murine infection model was used to demonstrate that the mutant invasive phenotypes were also observed in vivo. These data are most consistent with the idea that the rotation and physical orientation of flagella around the bacteria affect the ability of salmonellae to enter host cells. PMID- 1587618 TI - Binding and neutralization of endotoxin by Limulus antilipopolysaccharide factor. AB - In order to examine the ability of Limulus antilipopolysaccharide factor (LALF) to bind lipopolysaccharide (LPS), we purified LALF to homogeneity from Limulus amoebocyte lysate and coupled it covalently to agarose beads. LALF-coupled beads captured more tritiated LPS from rough and smooth strains of gram-negative bacteria than did control human serum albumin-coupled beads. Unlabeled homologous and heterologous LPS competed for the binding of 3H-LPS to LALF-coupled beads. LALF bound LPS in a dose-dependent manner as assessed by the precipitation of LPS LALF complexes with 50% saturated ammonium sulfate. We also studied the ability of LALF to neutralize LPS. LPS preincubated with LALF was less mitogenic for murine splenocytes, was less pyrogenic in the rabbit fever assay, was less lethal in mice which had been sensitized to LPS with actinomycin D, and induced less fever, neutropenia, and pulmonary hypertension when infused into sheep. Our findings extend prior studies which suggested that LALF binds to and neutralizes LPS from multiple strains of gram-negative bacteria. PMID- 1587619 TI - Mechanisms of Klebsiella pneumoniae resistance to complement-mediated killing. AB - The different mechanisms of Klebsiella pneumoniae resistance to complement mediated killing were investigated by using different strains and isogenic mutants previously characterized for their surface components. We found that strains from serotypes whose K antigen masks the lipopolysaccharide (LPS) molecules (such as serotypes K1, K10, and K16) fail to activate complement, while strains with smooth LPS exposed at the cell surface (with or without K antigen) activate complement but are resistant to complement-mediated killing. The reasons for this resistance are that C3b binds far from the cell membrane and that the lytic final complex C5b-9 (membrane attack complex) is not formed. Isogenic rough mutants (K+ or K-) are serum sensitive because they bind C3b close to the cell membrane and the lytic complex (C5b-9) is formed. PMID- 1587620 TI - Cytoskeletal composition of attaching and effacing lesions associated with enteropathogenic Escherichia coli adherence to HeLa cells. AB - The cytoskeletal lesions associated with enteropathogenic Escherichia coli adhering to cultured HeLa epithelial cells were examined by immunofluorescence microscopy. The microfilament-associated proteins actin, alpha-actinin, talin, and ezrin were localized with adherent enteropathogenic E. coli, whereas tropomyosin, keratin and vimentin (intermediate filaments), tubulin (microtubules), and vinculin were not localized. These cytoskeletal structures differed significantly from those associated with Salmonella typhimurium internalization (invasion). PMID- 1587621 TI - Characterization of the immunoglobulin A protease of Ureaplasma urealyticum. AB - Ureaplasma urealyticum strains of all serotypes express a specific human immunoglobulin A1 protease that cleaves immunoglobulin A1 to produce intact Fab and Fc fragments. The use of a variety of inhibitors suggests that the enzyme is a serine protease. N-terminal sequencing of the Fc digestion product showed that the enzyme cleaves between the proline and threonine residues 235 and 236 in the hinge region of the heavy chain of immunoglobulin A1. PMID- 1587622 TI - Early complement components enhance neutralization of Chlamydia trachomatis infectivity by human sera. AB - Immunoglobulin G in human serum neutralizes chlamydial infectivity in vitro. Complement-intact, C5-depleted, and C8-depleted human serum all have significantly more neutralizing activity than serum heated to inactivate early components of complement. Cobra venom factor, an analog of human C3b, enhances neutralization of antichlamydial immunoglobulin G in the absence of early complement components. PMID- 1587623 TI - Cell envelope proteins of Staphylococcus epidermidis grown in vivo in a peritoneal chamber implant. AB - Staphylococcus epidermidis was grown in vivo in chambers implanted intraperitoneally in rats. The cell wall and cytoplasmic membrane protein profiles of the in vivo-grown organisms were compared with those of S. epidermidis grown in vitro in nutrient broth (NB), in iron-restricted NB, or in pooled human peritoneal dialysate (HPD). Compared with growth in broth and in common with growth in HPD, growth in vivo in chambers resulted in the repression of many S. epidermidis wall proteins, with proteins of 27, 42, 54, and 70 kDa predominating. Growth in vivo also resulted in the induction of two iron repressible cytoplasmic membrane proteins of 32 and 36 kDa, which were also present in staphylococci grown in HPD and in iron-restricted NB. Immunoblotting experiments revealed that in sera taken 21 days after inoculation of the intraperitoneal chambers, the predominant antibody response to cell envelope proteins was directed against the 32- and 36-kDa iron-repressible membrane proteins. PMID- 1587624 TI - Biological exposure limit for occupational exposure to coal tar pitch volatiles at cokeovens. AB - Biological monitoring is an efficient tool in the evaluation of exposure to chemical agents. However, the dose-response of adverse health effects using biological exposure indices and biological limit values are rarely available. This paper presents an estimation of the occupational exposure limit value of 1 hydroxypyrene in urine, a biological exposure indicator of polycyclic aromatic hydrocarbons (PAH). A large-scale study of the exposure of cokeoven workers to PAH, in which both air sampling (benzene soluble matter and individual PAH including benzo(a)pyrene) and biological monitoring (1-hydroxypyrene in urine) were applied, made it possible to establish an empirical mathematical relationship between the air sampling data and biological monitoring data. It was calculated that cokeoven workers with a urinary concentration of 1-hydroxypyrene of 2.3 mumol/mol creatinine after a 3-day working period equals the airborne threshold limit value (TLV) of coal tar pitch volatiles (CTPV). Epidemiological studies have quantified the relative risk of lung cancer for topside and non topside cokeoven workers. The published environmental exposure data of topside and non-topside cokeoven workers were used to determine the time-average exposure. The data of 1-hydroxypyrene in the urine of cokeoven workers and data of epidemiological studies from different coke plants were combined according to the concentrations of PAH in the air. Thus, it was possible to establish an indirect relationship between lung cancer mortality risk and the biological exposure indicator for cokeoven workers. Exposure at the level of the suggested tentative biological exposure limit (BEL) of 2.3 mumol/mol creatinine is estimated to be equal to a relative risk of lung cancer of approximately 1.3. PMID- 1587625 TI - Epidemiological study of gastrointestinal and liver effects of carbon disulfide. AB - In the framework of an extensive health survey, 119 viscose rayon workers exposed to carbon disulfide (CS2) and 79 workers from other plants not exposed to any toxic agent in the working environment underwent a gastrointestinal examination including a self-administered questionnaire, abdominal palpation, percussion and a number of liver function tests. In the viscose rayon factory the working conditions have not changed since 1932. Personal monitoring performed in 17 jobs showed CS2 exposures varying from 4 to 112 mg.m-3. For each individual a cumulative CS2 exposure index (CS2 index) was calculated. Univariate analysis of the questionnaire findings showed significantly higher prevalences of anorexia (37.0% vs 11.4%, P less than 0.0001), vomiting (12.6% vs 3.8%, P = 0.04), and recent weight loss (10.9% vs 1.3%, P = 0.009) in the exposed than in the non exposed workers. The exposed workers had a larger total number of gastrointestinal complaints and a larger proportion reported at least one complaint at least once a month than the non-exposed ones. Abdominal tenderness was very rare in both groups. In multiple logistic regression analysis, adjusting for alcohol intake, smoking, body mass index (BMI), coffee consumption, commuting time, stress at work, shift work, educational level, family history of ulcer disease and intake of medication, significant associations with exposure were found for anorexia (P = 0.0001), nausea (P = 0.009), vomiting (P = 0.002) and flatulence (P = 0.03). Stress at work was a determinant for quite a few digestive complaints, but shift work was not significantly associated with any of them.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587626 TI - Smell or taste disturbances, neurological symptoms, and hydrocarbon exposure. AB - A total of 264 workers participated in a cross-sectional study concerning the toxicity of hydrocarbons. The clinical examination shows an increased prevalence of smell and/or taste disturbances in the heavily exposed group. These symptoms appear to be generally transitory and reversible. They seem to be due to concentration peaks rather than to a long exposure duration. They are associated with acute depressor effects and not with symptoms which could belong to a hydrocarbon-induced chronic toxic encephalopathy. PMID- 1587627 TI - Temporary threshold shift of temperature sensation caused by vibration exposure. AB - The temporary threshold shift of temperature sensation due to vibration exposure was studied to clarify the significance of frequency and acceleration on it. The discrete frequencies of the vibrations tested were 32, 63, 125, 250 and 500 Hz, and the accelerations were at the level of 2, 4, 8 and 16 g. The threshold shift of warm sensation (TTSw) was markedly, but that of cool sensation was small and not significantly different from the control value. TTSw increased with a rise in the level of acceleration and was largest at 125 Hz among the frequencies examined. The most effective frequency among the vibrations tested for warm sensation was inferred to be lower than that for vibratory sensation. After exposure, TTSw or the increment of the neutral zone decayed exponentially but bounced slightly in the later period. These patterns of TTSw are similar to those of the vibration-induced TTS of vibratory sensation. PMID- 1587628 TI - An immunoserological study of patients with vibration syndrome. AB - In a study undertaken to investigate the relationship between vibration syndrome and collagen disease, 90 Japanese patients with vibration syndrome (all men aged 41-86 years) were examined immunologic abnormalities, mainly by a set of immunoserology tests. Of these 90 patients, 25 had examinations at yearly intervals for 3 consecutive years, while the other 65 underwent examinations once. The results indicate that, of all the patients studied, 10 (11.1%) gave a positive RA test, 6 (6.7%) had leukopenia, 5 (5.6%) had hypergammaglobulinemia, and 15 (16.7%) had hypocomplementemia (CH50). Worthy of particular note are the 21 patients (23.3%) who were positive for nuclear-specific antibodies (1: greater than or equal to 40) (using Hep-2 cells as the nuclear substrate), with some of them suspected of having Sjogren's syndrome, progressive systemic sclerosis, or systemic lupus erythematosus. During a 3-year follow-up period, 10 (40%) of 25 patients exhibited rising titers of nuclear-specific antibodies with conversion to seropositivity for these antibodies. The facts that the positivity rate for nuclear-specific antibodies was significantly higher in these patients with vibration syndrome (23.3%) than in healthy adult men over 40 years of age (1.8%) (P less than 0.05) and that a progressive elevation of nuclear-specific antibody titer was noted in a high percentage of the patients were suggestive of some causal relationship between the appearance of nuclear-specific antibodies and the use of vibrating tools. PMID- 1587629 TI - Urinary cadmium and N-acetyl-beta-D-glucosaminidase excretion of inhabitants living in a cadmium-polluted area. AB - Urinary cadmium (Cd), N-acetyl-beta-D-glucosaminidase (NAG), and creatinine levels were determined for 400 inhabitants living in Cd-polluted districts of Annaka City in Gunma Prefecture, Japan. The Cd pollution was mainly due to falling dust from a zinc smelter factory according to seasonal winds. The Cd polluted areas were divided into five administrative districts around the factory. The geometric mean of the urinary Cd level of the inhabitants in the five districts, Nodono, Iwai, Ooya, Nakajyuku, and Itahana, were 2.95, 2.66, 2.45, 1.97, and 1.67 micrograms/g creatinine, respectively. The geometric means for Nodono and Iwai are statistically larger than that for Itahana (P less than 0.01). These results were well explained by the wind direction and proximity to the factory. In addition, a two-way analysis of variance on the urinary Cd level was made using place of residence and smoking habits. The effect was mainly due to the place of residence, and no interactions were found. There were statistically significant differences in NAG excretion among the five groups, but no difference could be found between two groups using a multiple comparison. Pearson's correlation coefficient between the logarithm of urinary Cd content and that of NAG was 0.203, but statistically significant (r = 0.462 without creatinine correction; P less than 0.01). The present results indicate the association of urinary Cd and NAG levels in a Cd-exposed population whose geometric mean of urinary Cd content is about 2 micrograms/g creatinine. We recommend a continuous survey of the minimum health effects of the Cd pollution using urinary levels of Cd and protein including NAG. PMID- 1587630 TI - Cancer risk among workers at a copper/nickel smelter and nickel refinery in Finland. AB - A total of 1,388 workers employed for at least 3 months at a copper/nickel smelter and nickel refinery were followed up for cancer from 1953 to 1987 through the Finnish Cancer Registry. There were 1,339 male and 49 female workers, making a total of 27,130 and 706 person-years, respectively. All of the women worked in the refinery, which opened in 1960, the same year the smelting of nickel began. A total of 67 cancers were diagnosed among the men, the standardized incidence ratio for all cancers being 1.0. No cancer was found among the women (1.8 expected). The risk of cancer among men was analysed according to primary site, exposure to nickel, type of work, years since first exposure and age at diagnosis. In the subcohort of nickel refinery workers, one case of sinonasal cancer was observed, against 0.02 expected, but otherwise no significantly increased risks of cancer were found. In addition to the small size of the cohort, the non-positive finding concerning lung cancer might be related to the relatively low arsenic exposure and, perhaps, to the late commencement of nickel production. PMID- 1587631 TI - Oxidative damage on DNA induced by asbestos and man-made fibers in vitro. AB - We compared the potential of asbestos and man-made fibers to attack DNA by the determination of the yield of 8-hydroxy-2'-deoxyguanosine (8-OH-dGuo) under several in vitro conditions. Asbestos induced 6.6-99.8 of 8-OH-dGuo per 10(5) dGuo in calf thymus DNA after 20 h of incubation, while the levels of 8-OH-dGuo in man-made fibers were low (3.6-9.4). The amounts of 8-OH-dGuo were strongly stimulated by the addition of H2O2 in asbestos, but not in man-made fibers. However, the yield of 8-OH-dGuo was induced more than that with asbestos by the further addition of FeSO4 in attapulgite, fiberglass, potassium titanate whisker, and metaphosphate polymer. The addition of ethylene diamine tetra-acetic acid (EDTA) promoted the induction of 8-OH-dGuo with asbestos and H2O2. The effects of mannitol (known as a hydroxy radical scavenger) were not dramatic on 8-OH-dGuo induction by all fibers except fiberglass and basic magnesium sulfate whisker, which induced higher amounts after mannitol addition than in these fibers and H2O2. Therefore, it was suggested that asbestos could damage DNA, resulting in 8 OH-dGuo as a cause of point mutation, and also several types of man-made fibers had similar effects to asbestos under certain conditions. PMID- 1587632 TI - Renal elimination of verbenols in man following experimental alpha-pinene inhalation exposure. AB - The renal elimination of verbenols after experimental exposure to (+) and ( )alpha-pinene was studied in humans following exposure to 10, 225, and 450 mg.m-3 terpene in an exposure chamber. The pulmonary uptake was about 60%. About 8% was eliminated unchanged in exhaled air. Depending on the exposure level, about 1%-4% of the total uptake was eliminated as cis- and trans-verbenol. Most of the verbenols were eliminated within 20 h after a 2-h exposure. The renal excretion of unchanged alpha-pinene was less than 0.001%. PMID- 1587633 TI - Effect of terfenadine on neutrophil and eosinophil chemotactic activities after inhalation of platelet-activating factor in vivo and on neutrophil chemotaxis in vitro. AB - In this double-blind crossover study we evaluated the effect of terfenadine on the rise in neutrophil chemotactic activity (NCA) and eosinophil chemotactic activity (ECA) in serum induced by platelet-activating factor (PAF) inhalation in 8 asthmatics. Additionally, we examined the direct effect of terfenadine on neutrophil chemotaxis in vitro in 7 allergic subjects. NCA and ECA in serum after PAF inhalation and neutrophil chemotaxis were measured using a modified Boyden chamber method. An initial elevation of NCA after PAF inhalation was inhibited by terfenadine, but the effect was diminished after subsequent PAF inhalations. Terfenadine showed no effect on ECA. In vitro PAF- and fMLP-induced neutrophil chemotaxis were significantly inhibited by terfenadine. These results suggest that terfenadine may have antiallergic properties in addition to its H1 receptor blockade. PMID- 1587635 TI - Antibodies for trypsinized human red blood cells in human sera. AB - During studies of agglutination of trypsinized human red blood cells (RBC) by anti-Rh sera, it was noticed that some human sera without Rh antibodies agglutinated these erythrocytes. Of 933 normal and pathological sera subsequently screened, 116 produced such agglutination. The agglutinins were of IgM nature and were directed against an antigen exposed or created by tryptic digestion of RBC. They reacted equally well with autologous as with allogeneic trypsinized RBC and were different from T agglutinins and from Paul-Bunnell antibodies. The mode of formation of these antibodies remains unknown. PMID- 1587634 TI - Effects of NZ-107 on bronchoconstriction in guinea pigs. AB - The effect of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ 107) on bronchoconstriction in guinea pigs was studied (1). The antigen-induced bronchoconstriction was studied in guinea pigs which had been passively sensitized by intravenous injection of antiserum containing anti benzylpenicilloyl bovine-gamma-globulin IgE antibody. The sensitized guinea pigs were divided into two groups; one group was pretreated with metyrapone (11 beta hydroxylase inhibitor in glucocorticoid metabolism) and the other with saline. The antigen-induced bronchoconstriction in the metyrapone-treated animals was more severe than that in the saline-treated animals. The asthmatic respiratory changes, in terms of prolongation of the ratio between expiration and inspiration, was also dramatically increased. NZ-107 at doses of 25 and 50 mg/kg significantly inhibited antigen-induced bronchoconstriction in both the saline and metyrapone-treated animals. NZ-107 showed a tendency to inhibit accelerated severe asthmatic respiration more strongly in metyrapone-treated animals than in those treated with saline. Salbutamol inhibited antigen-induced bronchoconstriction in saline-treated animals, but its efficacy decreased in metyrapone-treated animals. Unlike salbutamol, prednisolone and hydrocortisone showed the reverse effect, inhibiting bronchoconstriction in metyrapone-but not in saline-treated animals. Sodium cromoglycate inhibited antigen-induced bronchoconstriction in both saline- and metyrapone-treated animals (2). When a subthreshold dose of platelet-activating factor was injected into guinea pigs, airway responsiveness against histamine was clearly increased. NZ-107 at a dose of 0.2 mg/kg i.v. inhibited PAF-induced airway hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587636 TI - Inhibition of aeroallergen-induced bronchial eosinophilia by azelastine in guinea pigs. AB - The ability of azelastine to influence allergic bronchial eosinophil infiltration in guinea pigs was studied. Aeroallergen challenge of actively sensitized guinea pigs produces eosinophil infiltration in bronchoalveolar lavage fluid collected 20-24 h after aeroallergen exposure. Azelastine and methylprednisolone, administered orally 2 h before challenge, inhibited eosinophilic infiltration yielding the ED50s of 1.55 and 4.48 mg/kg, respectively. WEB-2086, a platelet activating factor antagonist (3 mg/kg), and theophylline, a phosphodiesterase inhibitor (30 mg/kg), also suppressed allergic bronchial infiltration of eosinophils by 44%. The data obtained in this study demonstrate that azelastine exerts direct bronchial anti-inflammatory activity in guinea pigs. PMID- 1587637 TI - In vitro study of platelets and circulating mononuclear cells of subjects presenting an intolerance to aspirin. AB - Aspirine-sensitive asthma (ASA) is a disease defined only by clinical criteria. It is an intrinsic asthma related to a hypersensitivity to aspirin. The illness is linked to abnormalities in platelet and macrophage arachidonic acid metabolism. We assessed in vitro the platelet chemoluminescence (CL) and lymphocyte proliferative response of ASA patients. We observed that platelets from patients and control do not generate any CL in the presence of aspirin. Concerning the proliferative response of lymphocytes, the in vitro effect of aspirin depends upon the origin of the lymphocytes tested. Thus aspirin clearly enhances the proliferative response of lymphocytes from normal subjects but diminishes the thymidine uptake by lymphocytes from ASA patients. This discrepancy in the in vitro response of lymphocytes from normal subjects and patients might be useful for in vitro diagnosis of ASA. PMID- 1587638 TI - The recognition of a recombinant human Fc epsilon fragment by the subclasses of IgG autoanti-IgE: disproportional subclasses distribution of complexed autoantibody. AB - Circulating IgG autoanti-IgE is detectable in a large proportion of individuals with allergic asthma where it is suggested to be potentially involved in the removal of IgE-allergen complexes. Since such a putative role will largely be determined by the subclass profile of complexed (i.e. IgE-bound) IgG anti-IgE, a study was undertaken to determine the subclass distribution of complexed IgG anti IgE antibody in the sera of asthmatic patients. The study exploits the heat labile property of IgE by heating (30 min at 56 degrees C) serum to liberate bound anti-IgE, pre- and post-heated sera are then assayed for IgG subclass anti recombinant human Fc epsilon (rFc epsilon) activities by ELISA and any heat induced increase in antibody activity is taken as a measure of complexed anti IgE. This has revealed a disproportionately high amount of IgG4 in complexed (but not free) IgG anti-IgE. The propensity of IgG4 to form complexes with IgE has important biological consequences, particularly with regard to the activation of C1q and Fc gamma R by other subclasses. PMID- 1587639 TI - Searching for the cause of the adult respiratory distress syndrome (ARDS) PMID- 1587640 TI - Biomaterials for blood tubing: the application of plasticised poly(vinyl chloride) PMID- 1587641 TI - Improved immunoglobulin production in dialysis patients treated with recombinant erythropoietin. AB - Improvements in B lymphocyte function have been reported in hemodialysis patients receiving erythropoietin. The present investigation studied whether erythropoietin interferes with B cell function and the mechanisms of this effect. Antibody production by cultured peripheral blood mononuclear cells (PBMC) (7 days) from 15 dialysis patients before and during erythropoietin treatment and from 14 healthy controls was followed. IgG and IgA were formed less in the uremic group than in healthy subjects. After 8 weeks of erythropoietin (hematocrit rose from 19 to 31%) basal IgG formation by PBMC rose from 304 +/- 83 to 566 +/- 49 ng/ml (p less than 0.02), while IgA production rose from 380 +/- 121 to 563 +/- 362 ng/ml (p less than 0.01). IgM production, which appeared to be normal in uremia, remained unchanged during erythropoietin treatment. Production of IgG and IgA stimulated by pokeweed-mitogen was subnormal in uremia, but improved under erythropoietin therapy. To establish whether erythropoietin acted by itself or through correction of the renal anemia, healthy PBMC were directly incubated with 2 U/ml of erythropoietin. Under these conditions production of IgG (+19%), IgA (+28%), and IgM (+32%) was enhanced. Taken together these data indicate a direct stimulant effect of erythropoietin on B lymphocytes in end-stage renal failure. PMID- 1587642 TI - Continuous ionography (CIG) in haemodialysis by ion-selective carrier membrane electrodes (ISCME) with solid cement contact for flow-through measurement. AB - Ion balance is of particular interest for patients maintained on RDT because of the importance of controlling ion movement and ion removal during haemodialysis. Continuous ionography (CIG) was therefore tested for electrolyte monitoring in extracorporeal haemodialysis in vitro and in vivo. The accuracy and stability of the electrodes were examined and various concentrations of potassium in blood, ultrafiltrate and dialysate were evaluated. Ion selective carrier membrane electrodes (ISCME) appeared to be suitable for continuous and simultaneous measurement of ions in blood and dialysis fluid. CIG monitoring of ion movement and ion removal could be the basis for adjusting and computer-managing ion elimination during extracorporeal haemodialysis. PMID- 1587643 TI - Simulation analysis of the influence of hemodialysis control parameters on exchange processes during therapy. AB - The effect of dialysis control parameters (dialysate composition, ultrafiltration rate, blood flow rate) on the patient's internal milieu were studied using a mathematical model for the description of the dynamic exchange processes during hemodialysis. This model simulates the electrolyte and water distribution, the acid-base and the oxygenation state as well as the ventilation. The dialysate sodium concentration affects mainly the intra-/extracellular water and the potassium distribution. The dialysate bicarbonate and acetate concentrations control the acid-base state and the electrolyte distribution (sodium and potassium). In addition, the dialysate acetate concentration has a strong effect on arterial oxygenation and on ventilation. The ultrafiltration rate controls the water distribution between plasma and the interstitial space but also the sodium distribution and the arterial acid-base state. The blood flow rate through the dialyser influences the acid-base state and, by this, it affects the potassium and sodium distribution. The acid-base state is affected in opposite directions when acetate or bicarbonate is used as a buffer. PMID- 1587644 TI - Tubing spallation in extracorporeal circuits. An in vitro study using an electronic particle counter. AB - The roller pump is the most common pumping device used in extracorporeal circulation (ECC). The interaction between the roller and tubing causes tubing spallation. Spallation has been associated with complications in ECC. Previous spallation studies present mixed results, including a decrease in the number of circulating particles. The objective of this work is to perform an in vitro study of tubing spallation which elucidates the causes of the particle sequestration, and the effect of tubing material, blood flow rate and duration of the procedure upon spallation. A sampling method minimizing background counts was devised. Silicone and PVC tubing were tested under normal and tight occlusion pressure at typical cardiopulmonary bypass and hemodialysis flow rates, for circulating times up to 4 h. Occlusion pressure and flow rate highly influenced the amount of spallation produced. Particle sequestration was noted and aggregation of the plastic particles was demonstrated. We conclude that, at least in vitro, aggregation causes the decrease in the particle counts and the misleading results obtained in most spallation studies using a Coulter counter. PMID- 1587645 TI - EC CO2R: oxygenator or hemodialyzer? An in vitro study. AB - In respiratory support of patients with acute respiratory distress syndrome (ARDS), the extracorporeal CO2 removal (EC CO2R) technique should be the earliest and easiest procedure so as to have the lowest blood flow rate. Extracorporeal circulation (ECC) can be achieved using an oxygenator for CO2 removal under the dry form (dissolved CO2) or a hemodialyser for CO2 removal under the wet form (bicarbonates). This study investigated different methods allowing an increase in CO2 transfer, using liquid flow rates up to 0.330 l/min. The experimental set-up employed heated (38 degrees C) aqueous polyelectrolytic solutions mimicking the venous blood (pH 7.20, PCO2 53 mmHg). Four in vitro methods were tested: Series I: a DIDECO D702 oxygenator without blood (= liquid) acidification, Series II: D702 oxygenator with inlet HCl acidification, Series III: a HOSPAL H10-10 hemodialyzer without dialysate alkalinisation, Series IV: H10-10 hemodialyzer with NaOH dialysate alkalinisation. Maximum gas flow in the oxygenator and dialysate rate in hemodialyzer were 5 and 0.55 l/min respectively. For the four series the CO2 transfer (TCO2) (mean +/- S.E. ml/min) and pH out were: [table: see text] The difference between the four series was statistically significant (t test). Acidification using the oxygenator increased CO2 transfer by 80%, but CO2 elimination was better with hemodialysis. PMID- 1587646 TI - Coronary hemodynamics during hemopump left-intraventricular assistance. AB - Hemopump left intraventricular pumping (HP) can permit percutaneous transluminal angioplasty (PTCA) in high-risk patients. Benefits may be related to left ventricular unloading or myocardial perfusion improvement, or both. Direct ultrasonic measurements of coronary blood flow were made in the dilated vessel after a successful PTCA in five patients. A 3 Fr intracoronary Doppler catheter was placed in the coronary artery to measure flow velocities (maximal or diastolic velocity; minimum or systolic velocity and mean velocity). A SwanGanz catheter was used to measure the cardiac index and pulmonary capillary wedge pressure. Mean aortic pressures were monitored through an 8 Fr guiding catheter. Measurements were made after a 5-min period of minimal speed (T0) of the HP to avoid retrograde regurgitation through the turbine; during the increase from minimum to maximal speed (T1); after a 5-min period of maximal HP flow (3l/min) (T2) and after HP was pulled back (T3). From T0 to T2, cardiac index rose from 1.93 +/- 0.38 to 3.26 +/- 0.35 l/min/m2 and capillary wedge pressure decreased from 18 +/- 6 to 13 +/- 5 mmHg (p less than 0.05); from T2 to T3, cardiac index decreased to 2.4 +/- 0.4 while capillary wedge pressure increased to 17 +/- 5 (p less than 0.05). Mean arterial pressure and heart rate did not change significantly throughout the study. When the hemopump flow was raised to high speed, coronary blood flow increased immediately but returned shortly to baseline values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587647 TI - Enhanced O2 transportation during cardiopulmonary bypass in piglets by the use of inositol hexaphosphate loaded red blood cells. AB - A continuous lysing and resealing of erythrocytes permitted internalization of inositol hexaphosphate (IHP), a strong allosteric effector of Hb, leading to significant rightward shifts of the HbO2 dissociation curve. Twelve piglets were put on cardiopulmonary bypass (CPB) with the heart beating, cooled to 25 degrees C then rewarmed to 37 degrees C before weaning off CPB. AoP, LV pressure, PAP, and cardiac output (CO) were monitored. Blood samples were taken before CPB, at 25 degrees C, at 30 degrees C, at 37 degrees C and after CPB for assessment of blood gases, arterio-venous difference in O2 content, lactates, P50 (partial pressure of O2 at 50% Hb saturation), and ionogram. Control group I included five pigs where the CPB circuit was primed with Ringer's lactate solution and porcine blood. In group II (n = 5), priming was done with Ringer's lactate solution and IHP loaded erythrocytes. P50 was significantly higher during CPB than before surgery in group II (20%), but not in group I (1%). There was a significant increase in VO2 in group II (6.02 ml/min) compared to group I (4.03 ml/min) (p less than 0.05) after CPB. Hemodynamics improved after CPB in group II (mean AoP 42 mmHg and syst LVP 70 mmHg) compared to group I (AoP 25 mmHg and syst LVP 22.5 mmHg). These preliminary results show that O2 transportation at the end of CPB is enhanced and myocardial function is improved in piglets with the use of IHP erythrocytes. PMID- 1587648 TI - Patterns of blood response during cardiopulmonary bypass. AB - Monitoring of cardiopulmonary bypass (CPB) in terms of alterations to the concentrations of selected blood constituents leads to contrasting patterns of response. This has been verified by determining the influence of CPB on the activation of fibrinolysis, complement, leucocytes and the contact phase of coagulation. Fibrinolytic activity was determined by fibrin degradation products (X-FDP's), complement activation by C3a and C5a, leucocyte activation by granulocyte elastase and contact activation by factor XII-like activity (FXIIA). Five patients undergoing elective coronary artery surgery using a bubble oxygenator and pulsatile perfusion were studied. X-FDP's rose gradually during CPB and remained elevated. Similar patterns were observed for elastase and FXIIA. In contrast, C3a rose sharply with peak values at 1 1/2-2h of bypass while C5a did not show significant changes during bypass. The data obtained have enabled the establishment of response patterns for parameters in CPB which will provide information relevant to the clinical application of biomaterials. PMID- 1587649 TI - A little local difficulty: the management of difficult-to-place people in Oxford. AB - So far we have outlined the cloud rather than the silver lining; and it is true, for example, that instances of "shared care that worked" could be found. But in general, the situation appeared to be that a small number of people posed difficult problems, often linked with aggression, for a range of agencies. It was perhaps ironic that many of the most difficult problems were picked up by the voluntary sector, which might be characterized as "the only place left to go" when statutory agencies decided that individuals had become too difficult to cope with. Interagency action was certainly possible, and attempted; but structural problems in its organization and differences of perspective between psychiatric and other agencies led to problems of implementation and sometimes to bad feelings. Part of the problem seemed to be that agency workers, in identifying individuals' needs, talked about the kinds of organizations that would be able to cope with the individuals. This limited their horizons. Individual "packages" of measures, perhaps in the form of "shared care," seemed eminently suited to the situation, provided they could be flexible enough to cope with quickly changing needs and provided that many of the relatively trivial details were systematically attended to--such as ensuring that everyone involved in a "package" knew the others' holiday dates. But this would not, by itself, be enough. Developments on these lines would also require movement in two other directions: on the one hand, to institute "top down" measures in the sense that the heads of agencies agree on the ground rules within which they could happen, and on the other, the delegation of more authority to rank-and-file workers to accept or refer cases. In some ways, this is a question of rethinking the forms of accountability within our statutory agencies. There will probably always be, as we have noted, a "rump" of people who cannot be helped perhaps because they do not wish to be; but the possibilities of more effective help and support for the rest were there to be grasped. PMID- 1587650 TI - Police as streetcorner psychiatrist: managing the mentally ill. PMID- 1587651 TI - Psychiatric, psychological, and legal models of man. PMID- 1587652 TI - Psychiatric testimony in Britain: remembering your lines and keeping to the script. PMID- 1587653 TI - Female follies: the forensic psychiatric assessment of women defendants. PMID- 1587654 TI - The individualizing function of forensic multidisciplinary assessment in a Dutch residential setting: the Pieter Baan Centre experience. PMID- 1587655 TI - Balancing care and control: guardianship, community treatment orders and patient safeguards. PMID- 1587656 TI - Primary telangiectasia of childhood. PMID- 1587657 TI - Non-psoralen treatment of vitiligo. Part II. Less commonly used and experimental therapies. PMID- 1587658 TI - Nomenclature of the primary telangiectasias. PMID- 1587659 TI - Nonsegmental vitiligo: decrease of the CD45RA+ T-cell subset and evidence for peripheral T-cell activation. AB - Peripheral T-lymphocytes from 16 randomly selected patients with nonsegmental vitiligo were labeled with monoclonal antibodies recognizing T-cell receptor (TCR) alpha/beta, TCR gamma/delta, CD3, CD4, CD8, CD45RA, CD45RO, CD11b, CD11c, CD16, CD56, CD25, CD54, and HLA-DR antigens. In comparison with matched controls, a significant decrease of the CD45RA+ subset (P less than 0.03) together with significant increase of the circulating HLA-DR+ cells (P less than 0.02) was found. No other alterations were detected. These findings may point to some autoimmune phenomena involved in the pathogenesis of the disease. The increased HLA-DR expression indicates the presence of activated peripheral T-cells. Thus, our data provide new and further evidence for T-cell dysregulation in nonsegmental vitiligo. PMID- 1587660 TI - Prevalence of dysplastic nevi in healthy young men. AB - Young white men (1176 men, mean age 20 years, age range from 18 to 26 years) were examined for dysplastic nevi. In 78 patients (6.63%), 107 clinically dysplastic nevi were observed, demonstrating all three NIH criteria (diameter greater than 5mm, irregularities of border, irregularities of color) suggestive for clinically dysplastic nevi. Of these, 71 nevi in 52 patients were excised and examined histologically, 46 nevi in 26 patients were not excised due to lack of patients' consent. Fifty-two of 78 (66.6%) patients with clinically dysplastic nevi agreed to excision. In these, seven nevi (13.5% of patients or 9.86% of all nevi excised) were confirmed by histology. According to these data, three additional patients with dysplastic nevi would have been expected among the 26 patients who refused surgery. Referring to the entire study group, the prevalence of dysplastic nevi in young white men is expected to be 0.85%. PMID- 1587661 TI - Dysplastic nevi, cutaneous melanoma, and gynecologic disorders. AB - We compared the frequency of reproductive system diseases and disorders among 206 female patients with dysplastic nevi (DN), and/or melanoma, in comparison with random samples of women of comparable age without melanoma. The highest odds ratio (OR) for these age-related diseases and reproductive disorders occurs among the youngest age group of the patients with DN alone (mean age 35.1 +/- 1.2 yr): 44.2% of the DN subjects had one or more reproductive disorders compared with 19.8% of the random sample (OR 3.2, 95% CL (1.6, 6.5), P less than 0.001). The patients with melanoma and DN (mean age 41.5 +/- 1.4 yr) also had a significantly greater percentage of subjects with one or more reproductive disorders, though less so than the DN subjects: 49.4% compared to 33.7% (OR 1.9, 95% CL (1.1, 3.3), P = 0.02). PMID- 1587662 TI - Benign neonatal hemangiomatosis. AB - Three neonates with numerous cutaneous hemangiomas are presented. Although all three had serious medical problems, in none of these three could visceral hemangiomas be demonstrated. Neonatal hemangiomas can be restricted to the skin. PMID- 1587663 TI - Psoriasiform sarcoidosis with ulceration. PMID- 1587664 TI - Vitiligo and polyglandular autoimmune syndrome with selective IgA deficiency. PMID- 1587665 TI - Linear and whorled nevoid hypermelanosis in a child with chromosomal mosaicism. PMID- 1587666 TI - Multiple pilomatricomas of the scalp. PMID- 1587667 TI - Unilateral Darier's disease associated with Hodgkin's lymphoma. PMID- 1587668 TI - Elemental mercury foreign body granulomas. PMID- 1587669 TI - Prevention of post-excisional wound infections: a comparison of oral cephalexin with topical mupirocin and topical cetrimide-chlorhexidine cream. PMID- 1587670 TI - William Cowper's anatomy of human skin. PMID- 1587671 TI - Tinea capitis caused by Microsporum canis in a newborn. PMID- 1587672 TI - Geographic tongue developing in a patient on lithium carbonate therapy. PMID- 1587673 TI - Treatment of psoriasis with aminophylline. PMID- 1587674 TI - Resolution of disseminated granuloma annulare with isotretinoin. PMID- 1587675 TI - Photodermatitis to aloe vera. PMID- 1587676 TI - Actinic prurigo. PMID- 1587677 TI - Parasites lost? PMID- 1587678 TI - Comparison of in vitro translation products of Sarcocystis gigantea and Sarcocystis tenella. AB - Poly(A)+ RNA was purified from cystozoites of Sarcocystis gigantea and Sarcocystis tenella and used to in vitro translate polypeptides in a wheat germ and a rabbit reticulocyte translation system. The in vitro translated polypeptides were compared by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The S. tenella mRNA translated at least two polypeptides (mol. wt about 80,000 and 21,500) in both translation systems that were not translated by the S. gigantea mRNA. To study co-translational and initial post-translational processing in Sarcocystis, the poly(A)+ RNA preparations were in vitro translated in the rabbit reticulocyte translation system in the presence or absence of canine microsomal membranes. Based on electrophoresis, there appeared to be modification of at least some Sarcocystis polypeptides in the mol. wt range 17,000-30,000. In addition, the translation products were immunoprecipitated with a homologous and a heterologous antiserum. The immunoprecipitated polypeptides were compared by electrophoresis and the S. tenella translation products contained at least one unique antigenic polypeptide with a mol. wt of about 34,700 that was not processed by the microsomal membranes. These results suggest that there is at least one polypeptide that is a candidate for use as an antigen for the differentiation of S. gigantea and S. tenella infections in sheep. PMID- 1587679 TI - Mitochondrial function in Babesia bovis. AB - A variety of anti-mitochondrial drugs that had previously been found to inhibit the growth of the malarial parasite Plasmodium falciparum were tested on Babesia bovis in vitro. Several of these drugs were found to be non-toxic towards B. bovis. However, those drugs that were found to inhibit babesial growth included compounds (shown in parentheses) that have the following putative mitochondrial targets in the parasite: ATP synthetase complex (rhodamine 123, oligomycin, Janus Green); ATP-ADP translocase (bongkrekic acid); electron transport (rotenone, n heptyl-4-hydroxyquinoline-N-oxide (HQNO), antimycin A); ubiquinone (CoQ) function (BW58C, menoctone); protein synthesis (tetracycline); and the proton pump (CCCP). We have also investigated the effects of some of these drugs on pyrimidine biosynthesis de novo by following the incorporation of [14C]bicarbonate into pyrimidine nucleotides and into the pyrimidine moieties of nucleic acids. The ubiquinone analogues BW58C and menoctone inhibited this pathway in the nM-microM range of concentrations. Inhibitors of electron transport (antimycin A and oligomycin) and an uncoupler (CCCP) were also effective inhibitors of pyrimidine biosynthesis de novo. We conclude that B. bovis has a functional mitochondrion that contributes significantly to pyrimidine biosynthesis de novo and to the overall energy metabolism of the parasite. PMID- 1587680 TI - Intergeneric relations between nematodes of the digestive tract in lambs: a multivariate approach. AB - The interactions between nematode genera of the ovine digestive tract have been examined through a multivariate analysis performed on data previously obtained in epidemiological surveys conducted in France and Morocco. Data referring both to the frequency of genera per sheep (analysis at the individual level) and to the number of worms per genus and per animal (analysis at the host population level) were examined. The results suggest that a highly stable equilibrium between genera occurred in individual hosts possibly regulated by the host response and the interactions between the worm populations. The regulative factors which act at the host population level tend to increase the stability of the system, to promote the expression of positive interactions between the genera and also to modulate the arrangement of intergeneric relations. The multivariate analysis thus provides a means for global analysis of the relations between nematode populations with potential applications to assess the efficacy of some control measures on the whole nematode community in the digestive tract. PMID- 1587681 TI - Analysis of acanthocephalan literature published since 1900. AB - The data for this study are based on more than 6000 articles that mention Acanthocephala. The results indicate: (1) the difficulty in being current on world literature. It took about 3 years beyond the date of publication to discover many articles. (2) Except for World Wars I and II there has been a sustained increase in the number of articles. At present this rate exceeds 1000 titles per 5-year period. (3) Investigator interest, as measured by multiple publications by a given author, has remained very small. (4) Most publications have originated in the U.S.S.R. and U.S.A. followed by Great Britain and Germany. (5) Number of authors per title has increased dramatically. Currently, there are more four-author than single-author articles. (6) Fish are host animals most likely to be mentioned as containing acanthocephalans. PMID- 1587682 TI - Retarded growth of Lucilia cuprina larvae on sheep and their sera following production of an immune response. AB - Attempts were made to immunize sheep against larvae of the sheep blowfly Lucilia cuprina using supernatant and pellet prepared by centrifuging (100,000 g max) homogenates from whole second instar larvae of L. cuprina or their excised guts. Injection of supernatant from whole larvae and from two fractions of this supernatant, prepared by ammonium sulphate precipitation, significantly reduced (by 24-58%) the final weight of larvae grown in vivo (i.e. on immunized sheep) for 20 or 44 h. Serum from animals vaccinated with supernatant from whole larvae reduced larval weights by 12% after growth for 20 h in vitro (i.e. on diet containing serum from treated animals). Pellet material from whole larvae or guts, when injected into sheep, stimulated an immune response which reduced the weight of larvae by 20-23% after 20 or 48 h in vitro. Larvae grown on these animals were not reduced in weight. Immunoglobulin (Ig) isolated from serum of a sheep vaccinated with gut material strongly retarded growth of larvae in vitro, the effect increasing with Ig concentration. These results indicate that an immune response in sheep, induced by injecting extracts of L. cuprina larvae, substantially reduces growth of this parasite. PMID- 1587683 TI - Comparative studies on the growth dynamics of two genetically distinct isolates of Giardia duodenalis in vitro. AB - The in vitro growth behaviour of the intestinal protozoan Giardia duodenalis was studied in detail and comparisons were made between two genetically and biologically distinct cloned isolates. Replicates of each clone were grown at six different initial cell concentrations and in culture media at four different pH values. Significant differences in in vitro growth were found between the two isolates, BAH12 and P1. BAH12 had a specific narrow pH requirement, with satisfactory growth only obtained at pH 6. The mean generation time of BAH12 at pH 6 between days 1 and 3 was 10.8 h, compared to an average of 6 h for the same period for P1, both at pH 6 and pH 7. Comparative health of cultures was assessed during both the pH and growth experiments using a suite of six variables. Consistent changes in the health of cultures over time were found to reflect growth behaviour over time. These results provide the first detailed evidence that genetically different isolates of Giardia may differ in such fundamental biological parameters as growth rate and pH requirements. These differences may have important epidemiological and taxonomic implications. PMID- 1587684 TI - On the ecology and distribution of Pseudoterranova decipiens C (Nematoda: Anisakidae) in an intermediate host, Hippoglossoides platessoides, in northern Norwegian waters. AB - The distribution of Pseudoterranova decipiens C helps demonstrate the ecological basis of this genetically defined sibling species. In northern Norwegian waters the major fish intermediate host is Hippoglossoides platessoides. Overall prevalence, mean intensity and intensity range in H. platessoides were 15%, 16.5 and 1-165, respectively. Outside the range of its only known definitive host, the seal Erignathus barbatus, the parasite was not found in the same intermediate host. PMID- 1587685 TI - A comparison of superoxide dismutase (SOD, EC:1.15.1.1) distribution in gastro intestinal nematodes. AB - An examination of the distribution of superoxide dismutase (SOD) activities in whole worm homogenates from six gastro-intestinal nematodes, at different life cycle stages, demonstrated that the third larval stages of each species contained notably more activity than the corresponding adults. Significant SOD activities were detected in culture fluids following in vitro maintenance of third and fourth larval stage and adult Trichostrongylus vitrinus and Teladorsagia circumcincta (formerly Ostertagia circumcincta). Marked interspecies variation was observed when SOD isoenzyme profiles of adult and third larval stage Nippostrongylus brasiliensis, Trichostrongylus vitrinus, Teladorsagia circumcincta and Haemonchus contortus were compared. In addition, SOD activity and isoenzyme polymorphism were greater in Nippostrongylus brasiliensis harvested from primed rats compared to parasites recovered from naive rats. PMID- 1587686 TI - Studies of stage-specific immunity against Trichostrongylus colubriformis in sheep: immunization by normal and truncated infections. AB - Sheep immunized with multiple normal infections of 30,000 Trichostrongylus colubriformis larvae (T.c. L3) suppressed the fecundity, establishment and survival of adoptively transferred adult worms, showing that these parasites were susceptible to the effects of host immunity. When sheep were immunized by four 'truncated' larval infections of 4, 7 or 10 days' (d) duration with 10(5) T.c. L3, animals given 4 x 4d infections were susceptible to challenge, whereas sheep given 4 x 7d and 4 x 10d infections were significantly protected. A serial analysis of the rejection of T. colubriformis from nine sheep given 5 x 7d infections revealed that the challenge larval infection given intraduodenally was expelled within 3 days after challenge (DAC). However, another five of these sheep only rejected around 50% of transferred adult worms by 21 DAC when compared with control animals. The results indicate that stage-specific antigens produced by early L3 and L4 stages of T. colubriformis effectively immunize sheep against a larval challenge but appear less reliably protective against adult worms. PMID- 1587687 TI - Studies of stage-specific immunity against Trichostrongylus colubriformis in sheep: immunization with adult parasites. AB - Merino sheep immunized by the adoptive transfer of adult T. colubriformis for 8 weeks were significantly protected against a challenge infection of 20,000 larvae. Two additional groups of sheep received a primary infection of 9000 adult worms which were allowed to persist for 14 weeks before one group was drenched. When both groups were challenged 10 days later with 30,000 larvae, serial necropsies of these and naive sheep revealed that worm rejection did not occur until 7-10 days after challenge. By comparison with the rapid rejection of larval challenges from sheep immunized with normal primary infections, the results suggest that the antigens which elicited rejection in these experiments are stage specific and were only present or synthesized in sufficient quantities when parasites had developed for 1 week. PMID- 1587688 TI - A serial study of rejection of Trichostrongylus colubriformis by immune sheep. AB - Host responses and the rejection of worms were measured at intervals following challenge of immune and susceptible sheep with T. colubriformis infective larvae. Immune sheep rejected most of their larvae within the first day after infection. This early rejection was associated with local appearance of globule leucocytes and increased concentration of T. colubriformis-specific IgG1 and IgG2 in intestinal mucus. Rejection of the remaining worms occurred between 3 and 14 days after infection and was associated with increased T. colubriformis-specific IgA and IgG2 in intestinal mucus, local T cell infiltration, activation, differentiation and epithelial necrosis. Local T cell changes included expansion of the T19- gamma delta+ populations in the villous lamina propria and epithelium. PMID- 1587689 TI - Experimental infection of Philippine Taenia in domestic animals. AB - In the present study, six 34-44-day-old Small-Ear-Miniature pigs and one 14-day old Holstein calf were each fed 10,000 Philippine Taenia eggs and sacrificed 27 43 days after inoculation. The infection rate was 100% for both pigs and calf with cysticerci recovery rates of 11 and 6%, respectively. A total of 6431 cysticerci were recovered only from the livers of the six pigs and 597 only from the liver of the calf; more occurred in the parenchyma (pigs 75%, calf 83%) than on the surface (pigs 25%, calf 17%). Mature cysticerci were found in four of the six pigs. A total of 317 cysticerci recovered from the pig livers were mature and the rest were either immature (926), degenerate or calcified (5188). All 597 cysticerci recovered from the liver of the calf were degenerate or calcified. Measurements of length, width, diameter of protoscolex, rostellum, and sucker and hooklet pattern indicated that Philippine Taenia is very similar to Taenia from Taiwan, Korea, Indonesia and Thailand and very different from classical T. saginata and T. solium. PMID- 1587690 TI - Interspecific differences in the movements of female ticks on reptiles. AB - Movements of females of two reptile ticks, Amblyomma limbatum and Aponomma hydrosauri were studied to determine whether the behaviour of the species on hosts was similar or different. Experiments were conducted to determine if the movement of females on hosts prior to mating was influenced by the delayed attachment of conspecific males. A field experiment was also undertaken to determine whether data obtained during laboratory experiments reflected the behaviour of females on hosts in the field. Both in laboratory and field experiments, a significantly greater proportion of Ap. hydrosauri females changed their site of attachment prior to mating. Individual Ap. hydrosauri females made significantly more positional changes than Amb. limbatum females. These interspecific differences occurred irrespective of the absence of conspecific males or presence of non-conspecific adults on hosts. These data may have important ecological implications in relation to the success of colonizing females at their parapatric boundary. PMID- 1587691 TI - A case of abdominal syndrome caused by the presence of a large number of Anisakis larvae. AB - A 58-year-old woman living in Shizuoka Prefecture, Japan, complained of severe epigastric pain and nausea about 8 h after having eaten 'Sashimi'. A gastrocamera examination undertaken as a result of her clinical history of gastric anisakiasis indicated that a large number of worms had penetrated the posterior walls. Fifty six larval nematodes were directly removed from the greater curvature of the stomach with a gastroendoscopic biopsy clipper, and were identified as the larvae of Anisakis simplex. PMID- 1587692 TI - Collagen shields and intraocular drug delivery: concentration of gentamicin in the aqueous and vitreous of a rabbit eye after lensectomy and vitrectomy. AB - Five albino New Zealand rabbits underwent bilateral lensectomy and vitrectomy. All left eyes were fitted with a collagen shield that had been soaked for 5 min in 2.0 mL of gentamicin solution (40 mg/mL for IV use). Right eyes were treated with fortified gentamicin drops (13.6 mg/mL) every 30 min for 12 hrs. Aqueous and vitreous specimens were obtained at the following time intervals: 1, 2, 4, 8, 12 and 24 hrs. We found the gentamicin concentrations to be higher in the aqueous of all eyes treated with fortified gentamicin drops. Only those eyes treated with fortified gentamicin drops attained a therapeutic drug level (4 micrograms-9 micrograms/mL) in the aqueous. Therapeutic drug levels were not attained in the vitreous of either treatment group. PMID- 1587693 TI - Clearance of microsphere-entrapped 5-fluorouracil and cytosine arabinoside from the vitreous of primates. AB - Experiments were conducted with biodegradable microspheres containing antimetabolites to assess the release of the drugs from the microspheres into the vitreous cavity of primates. Microspheres containing a mixture of radiolabeled and cold cytosine arabinoside (Ara-C) or 5-fluorouracil (5-FU) were prepared using a solvent evaporation process. The copolymers of poly (lactic) and poly (glycolic) acid (85:15) and drug was dissolved in a mixture of chloroform and acetone. The solutions were then emulsified in an aqueous solution of polyvinyl alcohol and stirred for 24 hours to evaporate the organic solvent. A 0.1 mL aliquot of a suspension of the microspheres was then injected into one eye of eight African Green monkeys. Half received 250 +/- 10 micrograms of Ara-C and the others 375 +/- 15 micrograms of 5-FU. The concentration in the vitreous was then measured by removing a 0.1 mL sample of vitreous at 1, 2, 4 and 11 days after injection. Both drugs released from microspheres were still detectable in the eye 11 days after injection and the clearance kinetics were similar for both drugs. The results indicate that the microspheres appear promising as a slow drug delivery system for future investigations in conjunction with these and other antimetabolites suitable for the treatment of PVR. PMID- 1587694 TI - Epikeratophakia: histopathological and cultural study. AB - Three epikeratoplasty buttons (one aphakic and two myopic) prepared by the freeze technique were removed two to nineteen months after surgery. A complete morphological and immunohistochemical study was performed on these buttons in order to gain insight into the reasons for epikeratophakia failure. Histopathological studies with light microscopy and scanning and transmission electron microscopy were performed. All three cases showed an anomalous process of re-epithelialization: in the first, the epithelium over the donor cap was almost completely absent, with many abnormalities; in the second, the epithelium was irregular, with a varying number of cell layers and poor adhesion between cells; in the third, the development of an epithelial cyst between the tissue lens and the cornea of the host caused the failure of the epikeratoplasty. The specimens were cultured 'in vitro' and the cells grown typed for HLA antigens. The antigen panel was the same as that of the host. Immunohistochemistry showed CD3- and CD8-positive cells in the stroma, proving the activity of T-suppressor lymphocytes in a cell-mediated immunoreaction. PMID- 1587695 TI - Extended-wear of high oxygen-permeable quantum contact lenses. AB - This study was performed to investigate the effects of extended-wear of rigid aspherical high gas-permeable contact lenses on the cornea. In the study 32 subjects (62 eyes) were followed over a period of 3 to 24 months. A high gas permeable contact lens (Dk 92), made of fluoro-silicone-acrylate copolymer, was used. Vision remained constant during the studied period. The corneal thickness decreased significantly (p less than 0.05) during the first six months. Significant changes (p less than 0.05) were found after three months in the corneal curvature, especially in the vertical meridian. No further topographical changes were noted in the period between three and six months of extended-wear. Complications, like acute red eye syndrome and bacterial infections, which may be encountered in soft lens extended-wear, were not noticed. At the end of the study 20 subjects (38 eyes, 61%) were still on extended-wear, 9 subjects (18 eyes, 29%) changed to daily wear and 3 subjects (six eyes, 10%) became unavailable for follow-up. Extended-wear of rigid aspherical high gas-permeable contact lenses may be considered as an acceptable alternative for soft lens extended-wear. PMID- 1587696 TI - Unnecessary surgery in fully refractive accommodative esotropia. PMID- 1587697 TI - Platelet aggregation, disc haemorrhage and progressive loss of visual fields in glaucoma. A seven year follow-up study on glaucoma. AB - Platelet aggregation in vitro, deterioration of visual field defects (VFD) and the prevalence of disc haemorrhages (DH) were assessed in 49 patients with primary open angle glaucoma (POAG) and compared with the findings for 67 individuals with suspected glaucoma (GS) in a seven-year follow-up study (range 5.8 to 8.2 years). The percentage patients with spontaneous platelet aggregation (SPA) was higher for POAG patients with visual field deterioration (60%) than both POAG patients without progressive loss of visual fields (12.5%; P less than 0.005) and those with suspected glaucoma (22.4%; P less than 0.005). The occurrence of DH was higher among POAG patients with progressive loss of visual field (28%) compared to the GS group (8.4%; P less than 0.025) and the group of patients consisting of POAG patients without deterioration of VFD and GS (9.9%; P less than 0.05). DH also occurred more often in patients with low tension glaucoma (41.6%) than in the remaining POAG patients (13.5%; P less than 0.05). No relation between the patients with SPA and the patients with DH was observed. PMID- 1587698 TI - Biological modifications of the vitreous in intraocular parasitosis: preliminary study. AB - In intraocular parasitosis the immunologic reactions in the vitrectomy-fluids depend on the parasitic agent: there is a lymphocytical reaction without any IgE production in toxoplasmic chorioretinitis, whereas there is a strong hypersensitivity reaction with a local IgE production as well as the presence of eosinophils and an antigenic stimulation in fluids with toxocara parasitosis. The electrophoretic patterns are quite similar in both cases. PMID- 1587699 TI - Flow patterns of blood cells in the retinal capillaries. Retinal capillary flow patterns. AB - We present a new technique for retinal blood cell angiography which was used to investigate flow patterns of blood cells in the retinal capillary net of normal cats. Capillary paths were defined to be the path taken by the labelled blood cells from the terminal arteriole to the entry point into a collecting venule. We were able to define two types of capillary paths. The 'simple' paths were minimally coiled and had a high blood cell flux. The 'complex' paths were coiled, structurally complex and had a low blood cell flux in comparison to the simple paths of the same eye. A simultaneous fluorescein angiogram was performed to reveal the complete anatomy of the capillary net in which the functional paths exist. The possibility that such flow patterns exist in the human retina should be considered. PMID- 1587700 TI - Uveal melanoma: therapeutic consequences of doubling times and irradiation results; a review. AB - Thirty-six of 39 published calculated doubling times (Td's) of uveal melanomas appeared to be longer than 60 days. Metastatic death occurs 35-40 Td's after dissemination. The shortest interval between dissemination and metastatic death in individual patients may, therefore, be calculated as 35 x 60 days = 6 years; the interval may extend to 80 years. This suggests, that local therapy cannot influence the survival data within the first 7 post-therapeutic years, because almost all metastatic deaths within these 7 years are due to pretreatment dissemination. For that reason, the published comparative survival analyses after various therapies have within this period failed to show statistically significant death rates differences. Microscopically viable melanoma tissue has been noted in 215 of 231 histopathologically studied irradiated uveal melanomas. Observed mitotic figures 4-6 years after irradiation indicate retained reproductive integrity. This constitutes a--by enucleation avoidable--incremental risk for post-irradiation exponential growth and dissemination. The risk cannot become statistically manifest before a greater than or equal to 10-year follow-up period. Retained, generally poor, visual acuity in a small percentage of patients cannot balance the incremental risk/benefit ratio of irradiation. A few, at present justifiable, indications for radiotherapy on uveal melanomas are enumerated. PMID- 1587701 TI - On the presence of dehydroascorbic acid in human plasma. PMID- 1587702 TI - Hepatic concentration of vitamin K active compounds after application of phylloquinone to chickens on a vitamin K deficient or adequate diet. AB - Liver and serum concentrations of vitamin K active compounds were measured in two groups of (deficient and normal) broilers after administration of phylloquinone 1 mg/kg. Assays were performed by HPLC after extraction and purification of these compounds. The only menaquinone found in the chicken was menaquinone-4. In the deficient group, the chickens exhibited hepatic concentrations of vitamin K1, vitamin K1 epoxide and menaquinone-4 markedly lower than those of the control group. After administration of phylloquinone, vitamin K and vitamin K epoxide levels fell sharply. There is no hepatic storage of vitamin K comparable to that of vitamin A. However, while menaquinone levels were found to be stable in the control group, they rose significantly in the deficient group after vitamin K injection. The question is: is there a transformation of vitamin K into menaquinone and/or is there a preferential utilization of one of the vitamin K active compounds? PMID- 1587703 TI - Blood vitamin and mineral levels in 7-17 years old Turkish children. AB - Blood vitamin (thiamin, riboflavin, vitamins B6, B12, C, A, and E, folate and beta-carotene), mineral (iron and zinc), alkaline phosphatase and cholesterol levels and hematocrit were assessed in 960 school-age children selected by random sampling from urban and rural regions of Turkey. Nutritional statuses of the children according to each index were compared with respect to age, sex, area and type of settlement. A biochemical deficiency was observed in 20.1% of the children for thiamin, in 89.9% for riboflavin, in 83.4% for vitamin B6, in 23.3% for folate, in 5.9% for vitamin B12, in 43.0% for vitamin C, in 11.6% for vitamin A, in 3.5% for beta-carotene, in 21.8% for vitamin E, in 6.1% for iron, and in 15.7% for zinc. Hematocrit was low in 54.3%. Alkaline phosphatase and cholesterol levels were found to be above normal in 54.6% and 4.9% of the children respectively. It is surmised that a major cause of the deficiencies was an ignorance of good dietary practice. Although the children were found to be relatively short according to the National Center for Health Statistics standards, their normalised weights were within acceptable limits, which suggested a prevalence of stunting but not wasting in this population. PMID- 1587704 TI - Dietary intake of vitamin A in African pre-school children in Umlazi, South Africa. AB - Vitamin A deficiency has been shown to have an impact on morbidity and mortality and therefore prevalence rates are important for public health policy. We report the use of a 7-day recall, dietary questionnaire, which was validated and administered to 203 randomly selected urban African pre-school children in Umlazi, South Africa. Common vitamin A containing foods eaten were leafy green vegetables, pumpkin, sweet potato, mangoes and chicken liver. Although the mean daily intake of vitamin A was adequate, 19 children had intakes below the recommended dietary allowance (RDA). Thirteen of these children had eaten liver in the previous week, and as such were probably not at risk. It is therefore estimated that only 6 of the children (3%) were at risk for developing vitamin A deficiency. PMID- 1587705 TI - Vitamin content of camel milk. AB - The content of vitamin C, vitamin B2 and fat-soluble vitamins E and A in camel milk was studied. The milk samples were collected from 20 individual camels (Camelus dromedarius) in two different occasions. The study showed that camel milk contains considerably less vitamin A and B2 than cow milk while the content of vitamin E was about the same level. The level of vitamin C was in average three times higher than that of cow milk. PMID- 1587706 TI - Microbiological methods of thiamine measurement in biological material. AB - Semiautomated, microbiological methods for the determination of thiamine in a variety of biological material are presented. Thiamine content was measured in bovine, ovine and rat blood, plasma, bile, urine, duodenal fluid, liver, kidney and brain. Thiamine was extracted from samples by mild acid digestion (trans aconitate pH 4.0) at 115 degrees C for 20 min. Microbiologic assays utilizing Lactobacillus fermenti and Ochromonas danica were performed on 96-well microplates and growth, as monitored by optical density, was directly read on a microplate reader at 650 nm. Particular attention was given to the validation of the two methods in terms of accuracy, reproducibility and recovery. The microbiological methods described here are specific, sensitive, and ensure good reproducibility. The methods can be used to analyse a large number of samples rapidly and at low cost. PMID- 1587707 TI - A jejunoileal bypass rat model for rapid study of the effects of vitamin malabsorption. AB - Jejunoileal bypass operation was originally done to promote weight loss for treatment of morbid obesity. We used such a model to determine if dietary vitamin absorption is compromised by such an operation. Six rats were subjected to a jejunoileal bypass, 6 control rats were pair-fed to bypassed rats; and 6 were fed ad libitum. Vitamin content of folic, B6, riboflavin, nicotinate, pantothenate, thiamin, biotin, B12, vitamins A, E, and carotene in blood and liver was determined after 8 postoperative weeks. Aside from riboflavin, blood vitamin levels were significantly depressed in bypassed rats. The deepest depression was seen for B12, carotene and vitamin E. Liver vitamin stores of folate, riboflavin, thiamin, B12, clearly were significantly depressed in the bypassed animals compared to the pair-fed and ad libitum-fed controls. This model can serve for rapidly studying micronutrient depletion due to malabsorption without dietary manipulation or antibiotics for gut sterilization. PMID- 1587708 TI - Long-term exposure of Wistar rats to high dietary sodium chloride level. I. Changes in aortic connective tissue components. AB - The effect of chronic salt loading on aortic components of connective tissue was evaluated in normotensive Wistar rats maintained on a high sodium chloride (NaCl; 8%) regime for a period of 30, 90, 180 and 360 days. The blood pressure remained unchanged until 90 days and was significantly elevated thereafter. The high NaCl diet for 180 days influenced neither the serum levels of both total cholesterol and triglyceride nor the aortic contents of collagen, elastin and glycosaminoglycans (GAG) derived from the proteoglycans. The only significant change associated with a 360-day massive NaCl ingestion was the increased aortic concentration of total GAG due to an increase in chondroitin sulfate, dermatan sulfate and heparan sulfate rather than hyaluronic acid. This study suggests that an increase in the contents of sulfated GAG occurred in the late stage of hypertensive aorta of NaCl loaded rats might be responsible, at least in part, for the pathogenesis of atherosclerotic cardiovascular disease. PMID- 1587709 TI - Long-term exposure of Wistar rats to high dietary sodium chloride level. II. Changes in hepatic drug-metabolizing and glutathione-related enzyme systems. AB - The effect of excess sodium chloride (NaCl) intake on hepatic drug-metabolizing and glutathione-related enzyme systems in rats was investigated for a period of 360 days. There was no change in any parameters studied until day 180 of the experiment. However, feeding of a 8% NaCl diet for 360 days produced a decrease in cytochrome P-450 content and an increase in glutathione peroxidase activity, and resulted in a lowered capacity of hepatic tissue to activate benzo[a]pyrene to mutagens detectable in the Ames bacterial mutagenesis assay. These observations suggest that although there may be little possibility of the involvement of high NaCl diet in the carcinogenic effects of benzo[a]pyrene, long term excess NaCl intake could reduce the potential for detoxification of many xenobiotic compounds leading to various pathological process. PMID- 1587710 TI - Relative bioavailability of iron in carbonyl iron and complex ferric orthophosphate to rat. AB - The relative biological availability (RBV of FeSO4.7H2O = 100%) of carbonyl iron and complex ferric orthophosphate in flour and bread baked with this flour was determined in a rat hemoglobin repletion assay. Hemoglobin iron gain and iron intake during repletion were used as dose-response parameters, and the relative biological values were assessed by the slope-ratio method. The RBV of carbonyl iron in flour was not calculated because the statistical validity of the slope ratio method was not fulfilled. The RBVs of all the tested iron sources were significantly lower than that of the ferrous sulphate standard (p less than 0.01). The RBV for complex ferric orthophosphate in flour was 45 +/- 8%, and for complex ferric orthophosphate and carbonyl iron in bread 36 +/- 7% and 35 +/- 7%, respectively. There were no differences in the bioavailability of carbonyl iron and complex ferric orthophosphate (p greater than 0.01). Baking did not effect the bioavailability of complex ferric orthophosphate (p greater than 0.01). PMID- 1587711 TI - Urinary excretion of iodide and fluoride from supplemented food grade salt. AB - Iodide and fluoride supplemented food grade salt (NaCl) is a common source of these two micronutrients. In a pilot study, we investigated whether increased intake of NaCl supplemented with iodide (I-) and fluoride (F-) results in their higher bioavailability. Twelve healthy adult human volunteers ingested increasing quantities (1, 3, 6 and 9 g) of NaCl with usual diet over 8 days. Sodium (Na+), I and F- were measured in 24 hour urine specimen. During the 4 day basal period when no additional NaCl was ingested, ingestion of NaCl calculated from urinary Na+ concentration and diuresis was 8.25 +/- 0.67 g/24 h. During the same period 0.11 +/- 0.01 and 0.61 +/- 0.04 mg of I- and F- respectively were excreted in the urine per 24 h. Increased ingestion of supplemented NaCl resulted in higher urinary excretion of sodium while urinary creatinine remained stable. 92% of I- and 40% of F- contained in the additional amount of NaCl ingested were excreted in the urine. These results indicate that with increased ingestion of supplemented (I- and F-) NaCl, almost the totality of I- is excreted in the urine while fluoride is either incompletely absorbed or retained by the body to a higher extent. I- and F- supplemented NaCl is, therefore, an effective vehicle to provide these micronutrients when ingested with diet. PMID- 1587712 TI - Comparative analysis of growth, diet, and urinary N excretion in elementary school children from urban and rural areas of Korea. AB - Weight and height measurements, dietary intake records and overnight urine samples for two days were collected from 38 children in Seoul and 36 children in rural area of Korea. Median percentages of height-for-age, weight-for-age and weight-for-height of the children in Seoul were significantly higher than those of the rural children. A mild degree of stunting was prevalent in the rural area, while overweight was more dominant among the children in Seoul. Dietary intake of energy, protein and fat as well as urinary excretions of N and creatine were also higher in the Seoul children. Animal protein intake correlated most significantly with height-for-age. Fat intake was a more important factor for weight-for-age and weight-for-height. Urinary excretion of N or creatinine, together with dietary factors, was a significant independent variable in regression models for the growth indices of the children. The results show the heterogeneity of nutritional problems among different subgroups of the Korean population at the present time. PMID- 1587713 TI - Development of vitamin-E-status of premature infants after intravenous application of all-rac-alpha-tocopheryl acetate. AB - A low vitamin-E-status was found in premature infants with birth weight less than or equal to 1,500 g. In this study the plasma vitamin-E-concentration of premature infants was analysed 2-3 h postpartal. During a total parenteral nutrition including fat emulsions the children received 4.5 mg all-rac-alpha tocopherol acetate/kg/d (approximately 3 mg rrr alpha-tocopherol equivalents/kg/d) intravenously for 5 days. On the same days control-infants received the same fat emulsions without supplemented vitamin E. Serum alpha tocopherol-levels were analysed on day 1, 3, 7 and 14 by HPLC. Initially the serum vitamin E level was 0.33 mg alpha-tocopherol/dl. Following the intravenous administration there was a significant increase in serum free alpha-tocopherol level. 7 days after end of supplementation the alpha-tocopherol concentration in serum reached 1,000 mg/dl serum. The highest level analysed after tocopheryl acetate supplementation was 2.45 mg alpha-tocopherol/dl. The choosen dose of 4.5 mg all-rac-alpha-tocopheryl acetate/kg body weight/day and this form of application were suitable to achieve normal serum alpha-tocopherol concentrations in premature infants without any complications. PMID- 1587714 TI - Absence of effect of retinol on the in vitro development of Plasmodium falciparum. PMID- 1587715 TI - Activity-dependent development of the vertebrate nervous system. PMID- 1587716 TI - A role for glial cells in activity-dependent central nervous plasticity? Review and hypothesis. AB - Activity-dependent plasticity relies on changes in neuronal transmission that are controlled by coincidence or noncoincidence of presynaptic and postsynaptic activity. These changes may rely on modulation of neural transmission or on structural changes in neuronal circuitry. The present overview summarizes experimental data that support the involvement of glial cells in central nervous activity-dependent plasticity. A role for glial cells in plastic changes of synaptic transmission may be based on modulation of transmitter uptake or on regulation of the extracellular ion composition. Both mechanisms can be initiated via neuronal-glial information transfer by potassium ions, transmitters, or other diffusible factor originating from active neurons. In addition, the importance of changes in neuronal circuitry in many model systems of activity-dependent plasticity is summarized. Structural changes in neuronal connectivity can be influenced or mediated by glial cells via release of growth or growth permissive factors on neuronal activation, and by active displacement and subsequent elimination of axonal boutons. A unifying hypothesis that integrates these possibilities into a model of activity-dependent plasticity is proposed. In this model glial cells interact with neurons to establish plastic changes; while glial cells have a global effect on plasticity, neuronal mechanisms underlie the induction and local specificity of the plastic change. The proposed hypothesis not only explains conventional findings on activity-dependent plastic changes, but offers an intriguing possibility to explain several paradoxical findings from studies on CNS plasticity that are not yet fully understood. Although the accumulated data seem to support the proposed role for glial cells in plasticity, it has to be emphasized that several steps in the proposed cascades of events require further detailed investigation, and several "missing links" have to be addressed by experimental work. Because of the increasing evidence for glial heterogeneity (for review see Wilkin et al., 1990) it seems to be of great importance to relate findings on glial populations to the developmental stage and topographical origin of the studied cells. The present overview is intended to serve as a guideline for future studies and to expand the view of "neuro" physiologists interested in activity-dependent plasticity. Key questions that have to be addressed relate to the mechanisms of release of growth and growth permissive factors from glial cells and neuronal-glial information transfer. It is said that every complex problem has a simple, logical, wrong solution. Future studies will reveal the contribution of the proposed simple and logical solution to the understanding of central nervous plasticity. PMID- 1587717 TI - Heterogeneity and regulation of nicotinic acetylcholine receptors. PMID- 1587718 TI - Acetylcholine at motor nerves: storage, release, and presynaptic modulation by autoreceptors and adrenoceptors. PMID- 1587719 TI - Voluntary active euthanasia. PMID- 1587720 TI - A model partnership. PMID- 1587721 TI - Euthanasia in The Netherlands. PMID- 1587722 TI - Euthanasia in The Netherlands. American observations. PMID- 1587723 TI - Euthanasia: normal medical practice? PMID- 1587724 TI - On regulating death. PMID- 1587725 TI - Paternalism no problem. PMID- 1587726 TI - Assisted suicide: can we learn from Germany? PMID- 1587727 TI - When self-determination runs amok. PMID- 1587728 TI - The usual suspects. PMID- 1587729 TI - Substituting our judgment. PMID- 1587730 TI - Sequencing the cycle. PMID- 1587731 TI - Washington's I-119. PMID- 1587732 TI - Role of modern imaging in decision-making for elective neck dissection. AB - This study examines patterns of early metastatic spread as recorded in 19 clinically negative, histologically positive (occult) neck dissection specimens. Microscopic metastatic deposits were detected in this study in nodes measuring 10 mm and less. No nodes with extension of tumor beyond the capsule and into adjacent structures were noted. Central necrosis was detected in only one node. We suggest that the first stages of metastatic disease as evaluated by the pathologist in clinically occult nodes are minimal and may easily evade the eyes of both pathologists and radiologists. Imaging proved to be efficacious in upstaging clinically occult necks that were previously irradiated. PMID- 1587733 TI - Serratus anterior muscle in composite head and neck flaps. AB - The serratus muscle (SAM) can be raised as an isolated muscular or osteomuscular flap on its nutrient vessels or in combination with a latissimus dorsi (LD) myocutaneous flap on the thoracodorsal pedicle for various reconstructive purposes. The aim of the present is to report on the results achieved after the use of the SAM alone (n = 7) and in combination with an LD (n = 3) after tumor resection or osteoradionecrosis (ORN) in ten patients with defects of the head and neck. One flap was lost due to venous thrombosis. The donor site morbidity was minimal. Emphasis is given on a new indication, namely ORN of the mandible. Short-term results show that the use of the SAM prevents a pathologic fracture in cases of a class IIIa osteoradionecrotic mandible. More extensive use of the SAM flap is advocated. PMID- 1587734 TI - Primary reconstruction of head and neck cancer with anterior rib, osteomyocutaneous composite flap. AB - The anterior rib, osteomyocutaneous composite flap (AROCF) incorporating both vessels, supracostal and intercostal, has been harvested for primary reconstruction in advanced head and neck cancer patients. The adequacy of the periosteal circulation alone for the successful free osseous transfer has been well proved. The available length of the internal mammary vessels is sufficient for the successful microvascular anastomosis in the neck. This same AROCF can be used as a pedicled flap based on the pectoralis major musculo-vascular pedicle for successful primary reconstruction in cases in which it is deemed unsuitable for use as a free flap. This is possible because of the unique functional blood supply of the rib. PMID- 1587735 TI - Electron beam therapy for skin cancer of the head and neck. AB - We retrospectively analyzed 99 patients with 115 sites of skin cancer, predominantly involving the head and neck, treated with electron beam therapy. Our objective was to determine the local control rate, radiotherapy reactions, cosmesis, and salvage treatment. Forty-three percent of patients received radiotherapy after biopsy, 41% were treated for recurrence following other modalities of treatment, and 16% had positive margins after surgical excision. With minimum and mean follow-up of 24 and 47 months, respectively, local control was achieved in 88% of patients. Six of 14 local recurrences were salvaged by surgery (five patients) and radiotherapy (one patient) for a total local control of 93%. Serial photographs and data were available to analyze cosmesis in 56 patients. Excellent or good cosmesis was achieved in 91%. Side effects were mild and self-limiting. EBT is highly efficacious and offers excellent cosmesis. PMID- 1587736 TI - Sublethal damage repair in squamous cell carcinoma cell lines. AB - Squamous cell carcinoma (SCC) cell lines recently established from head and neck tumors were studied for their capability of repairing sublethal radiation induced damage (SLDR). Total doses of 1.25, 2.50, 5.00, and 7.50 Gy were used either as a single dose or split in two equal fractions with a 24 h interval. Cell survival was determined using a 96-well plate clonogenic assay based on limiting dilution. Survival data was fitted by linear quadratic model, and the area under the survival curve (AUC) was obtained with numerical integration. The amount of SLDR was expressed as AUC-ratio comparing survivals from split dose vs single dose experiments. SLDR capacity was observed to vary markedly between individual cell lines (AUC-ratios 1.0-1.5). The relatively radiation-sensitive cell lines had a tendency toward higher SLDR proficiency (correlation coefficient 0.85). The differences in repair capacity could not be explained by the differences in doubling times of the cell lines. The inverse relationship between SLDR capacity and inherent radiosensitivity could explain the poor radiocurability of the sensitive donor tumors. Two of the most resistant cell lines were found SLDR deficient. This is a novel finding, since SLDR has been previously reported in all studied cells. PMID- 1587737 TI - Carcinoma of the nasopharynx: analysis of treatment results in 167 consecutively admitted patients. AB - Radiotherapy with curative intent was administered to 159 of 167 consecutively admitted patients with nasopharyngeal carcinoma. The classification (UICC 1982) gave the staging: stage I 8%, stage II 2%, stage III 28%, and stage IV 61%. The actuarial local tumor control was 54% and correlated to the T-classification. Primary control of neck nodes was 67% but was not correlated to the N-classes. Distant failure occurred in 20% of the patients; this was correlated to the N classification. The 10-year actuarially corrected survival rate was 37% (stage I+II 60%, stage III 49%, stage IV 27%). Late reactions were seen in 69%, and most patients had mild to moderate xerostomia. Men with high hemoglobin had a better prognosis than men with values in the lower part of the normal range. It is concluded that primary control in the T- and N-positions is the parameter most crucial to success. PMID- 1587738 TI - Value of clinical follow-up for local nasopharyngeal carcinoma relapse. AB - Three hundred seventy-nine new patients with nasopharyngeal carcinoma (NPC) were followed clinically and the physical examination, including that of the nasopharynx by indirect mirror for symptoms after treatment. At the time of analysis, with a median follow-up of 34.8 months, 47 patients had developed recurrent disease in the nasopharynx and in the immediately adjacent regions. In 31 patients the first clinical features to suggest local recurrence were progressive symptoms (group A). In another 13 patients recurrence of tumor in the nasopharynx was detected by indirect mirror examination (group B). In the remaining three patients, the diagnosis was made during investigation for neck node recurrence. The more common symptoms at diagnosis of local recurrence were headache; cranial nerve palsy involving the third, fourth, fifth, and sixth nerves; and ear and nasal symptoms. Group B patients tended to have less of these symptoms. The presence of tumor was confirmed by fiberscopic examination and biopsy in all group B patients and 14 of 31 group A patients, the tumor was submucosal in the remaining 17 group A patients. The recurrence in group B patients was diagnosed significantly earlier than the group A patients (p = 0.0294), and group A patients suffered from more invasive and extensive disease in comparison with group B patients (p = 0.0044). There were significantly less patients in group A who were amenable to curative brachytherapy (p = 0.0280). Clinical follow-up for local NPC recurrence was found to be useful. More frequent use of fiberscopic examination in the follow-up, especially for those not adequately examined by indirect mirror examination, will improve the detection rate. Cross-sectional imaging techniques and the monitoring of tumor markers may supplement clinical and fiberscopic examinations. An algorithm for diagnosing recurrent NPC and possible treatment are suggested. PMID- 1587739 TI - Psychosocial adjustment of patients surgically treated for head and neck cancer. AB - Sixty-six patients, surgically treated for head and neck cancer and free of disease, were interviewed at the outpatient clinic from 6 months to 8 years after surgery. The patients were divided by the physician into two groups, according to the patients' degree of disfigurement, i.e., minor (24 patients, 36%, minor disfigurement group = MDG) or extensive (42 patients, 64%, extensive disfigurement group = EDG). Subsequently, the patients were interviewed with close-ended questions. The following subjective aspects were assessed: self image; relationship with the partner, family, and friends; and the overall impact of the therapy. The results of the study showed a significantly higher impact in the EDG versus the MDG as regards a changed self-image (57% vs 25%, P less than 0.05), a worsened relationship with the partner (27% vs 0%, P less than 0.05), a reduced sexuality (74% vs 39%, P less than 0.01), and an increased social isolation (36% vs 12%, P less than 0.05). On the whole, 18% of the subjects stated that the disadvantages of therapy outweighed the advantages, and 30% fell that the difficulties encountered were "too harsh." In such cases, the opportunity of setting up a rehabilitation program offering psychosocial support should be considered. PMID- 1587740 TI - Value of grading squamous cell carcinoma of the head and neck. AB - We report a series of 3,294 patients with squamous cell carcinoma of the head and neck seen by one of us between 1963 and 1990. Two thousand and seven patients had a histologically proven and graded, but previously untreated, squamous cell carcinoma of the mucosal surfaces of the head and neck. These tumors had been graded previously by many different pathologists in many different hospitals, both in the United Kingdom and the United States, as well as continental Europe, over this period. Of the host factors both sex and age were associated with differentiation: 34% of patients less than age 50 had a well-differentiated tumor compared with 44% greater than age 50; 32% of women had a poorly differentiated tumor compared with 26% of men. General condition had no correlation with degree of differentiation. Site was closely associated with grading: well-differentiated tumors were more common in the mouth and larynx and poorly differentiated tumors in the pharynx. Furthermore, of poorly differentiated tumors, 19% arose from areas normally lined by keratinized squamous epithelium, 22% from a nonkeratinized area, 36% from respiratory epithelium, and 45% from areas normally covered by lymphoid epithelium. T stage had no significant correlation with differentiation. However, 46% of patients with poorly differentiated tumors had a nodal metastasis at presentation compared with only 28% of well-differentiated tumors. Distant metastases at presentation were found in 3.4% of poorly differentiated tumors compared with 1.8% of well-differentiated tumors. The survival fell significantly from 33% for well-differentiated tumors to 27% for poorly differentiated tumors. The recurrence rate at the primary site rose from 25% for well-differentiated tumors to 27% for poorly differentiated tumors, and recurrence in the lymph nodes rose from 26% to 30%. Both differences were just significant. PMID- 1587741 TI - Inflammatory pseudotumor of the parapharyngeal space: case report and review of the literature. AB - Inflammatory pseudotumor of the upper airway is an uncommon lesion of unknown etiology, clinically mimicking a neoplastic process. We document a case of inflammatory pseudotumor of the parapharyngeal space, occurring in a patient with history of cocaine abuse. Corticosteroid treatment was successful in reducing the symptoms. The difficulties in establishing this clinicopathologic diagnosis are discussed and the pertinent literature is reviewed. PMID- 1587742 TI - Burn of the auricle. AB - Silvadene cream and Sulfamylon make up the treatment regimen for one contributor (Dr. Crumley). No systemic antibiotics would be given. Any areas of obvious third degree burns would be debrided and grafted. The tympanic membrane perforation would be treated with antibiotic/steroid drops. The second author concurs with use of Silvadene cream and would avoid any pressure on the area (Dr. Abemayor). While he agrees that systemic antibiotics should be avoided, he also would not prescribe ear drops. He recommends evaluation for a pulmonary or ophthalmologic injury. There is a disagreement regarding imaging studies. One expert would order a CT scan to rule out facial fractures (Dr. Crumley). His counterpart would not order a CT but would check a baseline chest x-ray if there were any sign of pulmonary compromise (Dr. Abemayor). Both experts would obtain an audiogram after the acute problems are treated. In the case of foul drainage, burn reconstruction would be delayed. In addition to treating the otorrhea with ear drops, one physician would add oral antibiotics (Dr. Abemayor). The other author believes tympanoplasty should be performed prior to reconstruction (Dr. Crumley). There were several procedures suggested for the reconstruction. Both authors discuss a method of creating a postauricular pocket, burying the ear pedicle, and using costal cartilage for an inlay helical graft. Another approach involves minimal debridement of the cartilage and letting the wound mature for 6 to 8 months. At that time the area would be debrided and the postauricular skin used for external coverage (Dr. Crumley). If the facial scar is a cosmetic problem 1 year after the injury, triamcinolone injections and local massage should be considered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587743 TI - Outpatient and short-stay thyroid surgery. PMID- 1587744 TI - Influence of sulphate groups in the binding of peanut agglutinin. Histochemical demonstration with light- and electron-microscopy. AB - The influence of sulphation of mucus glycoproteins in the binding of peanut agglutinin (PNA) to tissue sections has been investigated by means of histochemical techniques at the light- and electron-microscopic level. A sequential methylation-saponification procedure was applied for the desulphation of tissue samples. Labelling by peroxidase- and colloidal gold-conjugated PNA was compared in control and desulphated samples of rat intestinal mucosa. The high iron-diamine (HID) technique was used as a control for the effectiveness of the desulphation technique, and the Alcian Blue, pH 2.5 (AB 2.5), PAS and phosphotungstic acid-HCl (acid-PTA) techniques served as controls for the integrity of the oligosaccharide chains, respectively. In general, a marked increase of PNA reactivity was observed in desulphated samples when compared with control sections. These findings indicate that sulphation of galactose inhibits the binding of PNA to carbohydrate moieties in tissue sections. Staining patterns obtained with HID, PNA and the desulphation-PNA sequence in the goblet cells of the large intestine suggest a modification of the secretory product stored in these cells as the cell matures and moves from the lower crypt region toward the luminal surface. These modifications were not detected in the small intestine. Ultrastructural detection of PNA-binding sites suggests that galactose residues are incorporated into the oligosaccharide chains of O-linked glycoproteins at the medial cisternae of the Golgi apparatus. However, sulphation occurs at the trans side of the Golgi complex and the trans Golgi network. In conclusion, desulphation procedures are useful for revealing PNA-binding sites. PMID- 1587745 TI - Retrospective analysis of 5037 patients with nasopharyngeal carcinoma treated during 1976-1985: overall survival and patterns of failure. AB - This is a retrospective analysis of 5037 patients with squamous cell carcinoma of the nasopharynx treated during the years 1976-1985. The stage distribution according to Ho's classification was 9% Stage I, 13% II, 50% III, 22% IV, and 6% Stage V. Only 4488 (89%) patients had a full course of megavoltage radiation therapy. The median equivalent dose to the nasopharyngeal region was 65 Gy and cervical region in node-positive patients 53 Gy. Seventy percent (906/1290) of the node-negative patients had no prophylactic neck irradiation. The overall actuarial 10-year survival rate was 43%, and the corresponding failure-free survival 34%. Altogether, 4157 (83%) patients achieved complete remission lasting more than 6 months, but 53% (2205/4157) of them relapsed after a median interval of 1.4 years. The 10-year actuarial local, regional, and distant failure-free rates were 61%, 64%, and 59%, respectively. Thirty-eight percent (338/891) of all patients with local recurrence achieved second local remission. The local complete remission rate with aggressive re-irradiation alone was 47% (333/706). But 37% (124/338) of the responders recurred the second time. The incidence of distant failure correlated significantly with both the N-stage and the T-stage, with the highest (57%) occurring in patients with N3 disease. The incidence of nodal relapse in node-negative patients was 11% (44/384) among those given prophylactic neck irradiation, but 40% (362/906) among those without. Therapeutic irradiation achieved a complete regional remission rate of 90% (306/339). However, despite successful salvage, these patients had a significantly higher distant failure rate than those without nodal relapse, even if they remained local-failure-free (21% vs 6%). Patients treated during 1981-1985 achieved significantly better treatment results than those treated during 1976-1980, especially in terms of the overall survival (57% vs 47% at 5-year), the overall failure-free survival (42% vs 35% at 5-year), and the local failure-free rate (70% vs 63% at 5-year). The possible contributing factors are discussed. PMID- 1587746 TI - Carcinoma of the nasopharynx: factors affecting prognosis. AB - This is a retrospective analysis of 143 patients with histologically confirmed epidermoid carcinoma of the nasopharynx treated with definitive irradiation. Patients were treated with a combination of Cobalt-60, 4 to 6 MV X rays, and 18 to 25 MV X rays to the primary tumor and the upper necks, excluding the spinal cord at 4000 to 4500 cGy to total doses of 6000 to 7000 cGy. At 10 years the actuarial primary tumor failure rate was 15% in T1, 25% in T2, 33% in T3, and 60% in T4 lesions. The corresponding failure rate in the neck was 18% for N0, 14% for N1, and 33% for N2 and N3 lymphadenopathy. The incidence of distant metastasis was related to the stage of the cervical lymphadenopathy: 16% in patients with N0 N1 nodes compared with 40% in the N2-3 node group. The actuarial 10-year disease free survival rate was 55% to 60% for T1-3N0-1 tumors, 45% for T1-3N2-3 tumors, 35% for T4N0-1, and 20% for T4N2-3 lesions. The overall 10-year survival rate was about 40% for patients with T1-2N0-1 tumors, 30% for those with T3 any N stage tumors, and only 10% for the patients with T4 lesions. Multivariate analysis showed that tumor stage and histological type, cranial nerve involvement, patient age, and doses of irradiation to the nasopharynx were significant prognostic factors for local/regional tumor control. Increasing doses of irradiation resulted in nasopharynx tumor control in 80% of the patients receiving 6600 to 7000 cGy and 100% of those receiving over 7000 cGy in the T1, T2, and T3 tumors. However, the tumor control rate did not rise above 55% even for doses over 7000 cGy in the T4 lesions. Local tumor control was higher in patients who had simulation (55/78 = 71%) compared with those on whom simulation was not performed (34/61 = 56%) (p = 0.10). Moreover, patients with more than 75% of the reviewed films judged as adequate had 69% primary tumor control (66/96) compared with 53% (23/43) for those with fewer than 75% adequate portal films (p = 0.07). PMID- 1587747 TI - The predictive role of bioeffect dose models in radiation-induced late effects in glottic cancers. AB - Late radiation-induced laryngeal oedema for different doses per fraction was analyzed in 208 cases with squamous cell carcinoma of the vocal cord. The series comprised 156 cases with T1N0M0 and 52 cases with T2N0M0 lesions. Radical radiotherapy was given with three different regimens delivering 3.33 Gy, 2.5 Gy, and 2.25 Gy per fraction. There were 52 cases of late radiation-induced laryngeal oedema. A strong correlation (p less than 0.015) between the dose per fraction and the risk of the late complication in the vocal cord has been demonstrated. The analysis suggests that the empirical models like Nominal Standard Dose (NSD) or Time-Dose Factors (TDF) do not predict correctly the late normal tissue reactions for different dose fractionations. The analysis with extrapolated response dose (ERD) values of the linear-quadratic (L-Q) model also fail to correlate with the late complications (p greater than 0.5). Care should be exercised when using these bioeffect dose models to calculate regimens iso effective for late damage, even when modest changes in fraction size from 2 to 3 Gy are contemplated. PMID- 1587748 TI - Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis. AB - Although prognostic variables for locoregional recurrence of breast cancer have been evaluated by univariate analysis, multifactorial analysis has not been previously performed. In the present study, survival following chest wall and/or regional lymphatic recurrence was determined in 230 patients with locoregionally recurrent breast cancer without evidence of distant metastases treated at the Radiation Oncology Center, Mallinckrodt Institute of Radiology and affiliated hospitals. Multifactorial analysis demonstrated that the site of recurrences correlated most strongly with overall survival (p = 0.001). The 5-year actuarial overall survival was 44-49% for patients with isolated chest wall, axillary, and internal mammary lymph node recurrence. Patients with either supraclavicular, multiple lymphatic, or concomitant chest wall and lymphatic recurrence had an 21 24% 5-year overall survival. The 5-year disease-free survival was 28-37% for patients with chest wall, axillary, or internal mammary recurrences compared to 4 13% for those with supraclavicular, chest wall and lymphatic, or those with multiple sites of lymphatic recurrence. Disease-free interval from mastectomy to recurrence was also found to be a significant prognostic factor for overall survival (p = 0.005). Fifty percent of patients with a disease-free interval of at least 2 years survived 5 years following locoregional relapse, compared to 35% for those with disease-free interval of less than 2 years. In the subset of patients with small chest wall recurrences (excised or less than 3 cm) and a disease-free interval of at least 2 years, the 5-year overall and disease-free survivals were 67% and 54%, respectively. These results suggest that subsets of patients with locoregional recurrence of breast cancer can survive for long periods of time. The conventional wisdom that chest wall and/or regional nodal recurrence following mastectomy uniformly confers a dismal prognosis is not necessarily true. PMID- 1587749 TI - Comparison of pathologic and clinical evaluation of lymph nodes in prostate cancer: implications of RTOG data for patient management and trial design and stratification. AB - RTOG 77-06 and 75-06 were studies of nodal irradiation in prostate cancer, for which the status of nodes was determined by lymph node dissection (LND), lymphangiography (LAG), or computer assisted tomography (CT) based on investigator preference. Actuarial 5 year endpoints of survival, NED survival, local recurrence and distant metastasis have been determined by stage for 805 eligible patients with a comparison of pathologic vs clinical (imaging test) determined nodal status. Patients with pathologically negative lymph nodes show significantly improved 5 year survival (Stage T-2 (B) 84% vs 77%, Stage T-3,4 (C) 82% vs 65%) and NED survival (Stage T-2 (B) 72% vs 63%, Stage T-3,4 (C) 64% vs 44%) compared to patients clinically negative. Free of metastasis rates are increased in Stage T-3,4 (C) pathologic negative patients compared to imaging negative patients (75% vs 60%). A comparison of clinical positive versus clinical negative patients shows no difference in survival, NED survival or rate of metastasis, while a similar comparison of pathologic positive versus pathologic negative shows significant difference for all three endpoints (survival: Stage T 2 (B) 84% vs 61%, Stage T-3,4 (C) 82% vs 66%, NED survival: Stage T-2 (B) 72% vs 32%, Stage T-3,4 (C) 64% vs 32%; free of metastasis: Stage T-2 (B) 82% vs 64%, Stage T-3,4 (C) 75% vs 44%). The clinical determination of nodal status, therefore, has no prognostic value in contrast to pathologic determination and should not be used for stratifying patients in clinical trials. The CT scans often used to evaluate nodal status are more useful if delayed until they can be done as part of the treatment planning process where the CT has value. When imaging tests suggest positive lymph nodes in prostate cancer patients, the imaging finding is confirmed by biopsy. PMID- 1587750 TI - T1 and T2 carcinoma of the urinary bladder: long term results with external, preoperative, or interstitial radiotherapy. AB - Between January 1974 and December 1984, 273 consecutive patients with cancer of the urinary bladder, Stages T1 or T2, any N, M0, were referred to the radiotherapy department of the Catharina Hospital at Eindhoven, The Netherlands and 265 were treated in a non-randomized fashion according to one of the three following schedules: 137 patients (67 T1, 70 T2) received radiotherapy only; 96 (44 T1, 52 T2) had preoperative radiotherapy followed by cystectomy and diversion according to the Bricker technique in 94/96; 32 patients (13 T1, 19 T2) had low total dose (12 Gy median) external radiotherapy followed by an interstitial cesium implant. The external radiotherapy fields included the pelvic structures. Total dose was 64 Gy median in the radiotherapy-only group and 40 Gy median in the preoperative irradiated group. The median follow-up in survivors was 81 months (range: 15-203). Locoregional relapse was observed in 50% in the group treated by external radiotherapy alone versus 17% in the group treated by preoperative radiation plus surgery and 28% of the patients who received cesium implant. During follow-up, 106/137 (77%), 67/96 (70%) and 13/32 (41%) patients died. In the radiotherapy-alone group, 38 died from intercurrent diseases, 36 from bladder cancer, two from therapy-related complications and cause of death was unknown in 30 patients. In the preoperative radiation group, the figures were 17 for intercurrent deaths, 26 related to progressive bladder cancer, 14 died due to perioperative complications and cause of death was unknown in 10. Cause of death was intercurrent in six and due to bladder cancer in seven patients treated by cesium implant. Probability of survival (calculated from the date of histological diagnosis) for the whole group, with censoring death to intercurrent disease was 53% at 5 years (56% for T1; 51% for T2) and 41% (40% for T1; 43% for T2) at 10 years. No significant difference was observed between T1 and T2 (p = 0.76). Survival in the treatment subgroups was, for patients treated by external radiotherapy only: 50% at 5 years and 33% at 10 years; for patients treated by external radiotherapy and surgery: 49% at 5 years and 42% at 10 years; for patients treated by cesium implant: 76% at 5 years and 76% at 10 years. Survival of patients in the cesium implant group was significantly better than in the other groups (p = 0.0001). Following variables were analyzed using the Cox proportional hazards model: age, gender, T1 or T2 stage, grade, cesium implant or not, and surgery or not.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1587751 TI - Long-term results of combined modality treatment with I-125 implantation for carcinoma of the pancreas. AB - From 1981 to 1987, 81 patients with localized, unresectable carcinoma of the pancreas were treated at Thomas Jefferson University Hospital with a combination of intraoperative Iodine-125 implantation, external beam radiation, and peri operative systemic chemotherapy. Fifty patients had Stage II disease and 31 patients had Stage III disease. Radioactive Iodine-125 seeds were implanted intraoperatively into the tumor to deliver a minimum peripheral dose of 12,000 cGy over one year. This was followed by external beam radiation (50-55 Gy) and systemic chemotherapy (5-FU, Mitomycin-C +/- CCNU). Incidence of peri-operative mortality was 5% (4/81). Early morbidity was observed in 34% of patients and late complications in 32%. A median survival of 12 months and 2- and 5-year survival rates of 21% and 7% were observed. The determinate 2- and 5-year survival rates were 28% and 13%, respectively. The overall 2- and 5-year survival rates with Stage II disease were 27% and 8% and for Stage III disease, 13% and 3%, respectively (p less than 0.05). The determinate 2- and 5-year survival rates were 34% and 19% for Stage II and 19% and 5% for Stage III disease, respectively (p = 0.08). Local control of disease was achieved in 71% of patients. This combined modality approach appears to have achieved satisfactory local control of primary cancer and long term survival of selected patients. PMID- 1587752 TI - Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy. AB - Ninety-three patients with primary intracranial ependymoma were treated at the Royal Marsden Hospital, between 1952 and 1988, with postoperative radiotherapy. The survival probability at 5, 10, and 15 years was 51%, 42% and 31%, respectively, and the corresponding progression free survival (PFS) probability, 41%, 38%, and 30%. Tumor grade was the single most important prognostic factor for survival and PFS with gender of lesser prognostic significance. Treatment parameters were stratified for grade. In patients with low grade tumors survival and PFS were better following complete macroscopic excision compared to incomplete surgery. The extent of resection had no significant influence on survival or PFS in patients with high grade tumors. Extent of irradiation did not influence PFS, irrespective of tumor grade, while patients with high grade tumors had marginally better survival following extensive irradiation compared to more limited radiotherapy. The main problem in the treatment of ependymoma remains local progression which was the cause of death in all but two patients. New treatment strategies should focus on improvement of local control, especially in incompletely resected low grade tumors and all high grade tumors. The use of spinal irradiation is unlikely to significantly improve treatment results. PMID- 1587753 TI - Patterns of recurrence of malignant astrocytoma following stereotactic interstitial brachytherapy with iodine-125 implants. AB - The pattern of tumor recurrence was studied in a series of 68 patients who were treated with interstitial brachytherapy for malignant astrocytoma. Thirty-six patients had newly diagnosed tumors and were treated following surgery and external beam therapy, while 32 were treated for recurrent tumors. Recurrence pattern was determined using computed tomography at the time of clinical deterioration. Thirty-eight percent of tumor recurrence occurred within the original tumor margin and 50% occurred at the original site but extended beyond the initial margin. In all, 88.0% recurred at the initial tumor site, 71.4% being confined to within 2 cm of the pretreatment tumor borders while 6.0% recurred intracranially outside of the initial tumor margin. One patient recurred with spinal metastasis while two patients developed systemic metastases. The significance of these findings is discussed. PMID- 1587754 TI - Subcutaneous or topical administration of 16,16 dimethyl prostaglandin E2 protects from radiation-induced alopecia in mice. AB - Alopecia, a common sequel of radiation treatment of brain tumors, increases patient stress to the extent that refusal of treatment may occur. The expectation that loss of hair will be prevented, or that regrowth will occur, is extremely important to patients. To investigate prostaglandin-induced radiation protection against alopecia, the hair of B6D2F1 male mice was plucked from the right thigh and surrounding area to induce anagen. Fourteen days later, mice were injected subcutaneously in the neck with 10 micrograms 16,16 dm PGE2 in 0.2 ml of vehicle, or with the vehicle alone. In another group of previously plucked mice, 16,16 dm PGE2 in the same concentration, or the vehicle was applied topically. One hour later, graded single doses from 6.5 to 12.5 Gy 137Cs gamma irradiation were given to groups of six animals. On day 21 post-plucking, all animals were killed and a portion of the irradiated site was excised. The average hair counts per field in irradiated animals were 85 +/- 4 (6.5 Gy), 25 +/- 5 (8.5 Gy), and 5.5 +/- 0.7 (10 Gy). Animals receiving the prostaglandin systemically had values of 60 +/- 10 (6.5 Gy), 54 +/- 3 (8.5 Gy), 66 +/- 6 (10 Gy), and 30.1 +/- 8 (12.5 Gy). Topical application of the prostaglandin resulted in protection that yielded 52 +/- 3 (8.5 Gy), 34 +/- 4 (10 Gy), and 3.2 +/- 0.9 (12.5 Gy) hairs per field. Both systemic and topical application of 16,16 dm PGE2 protected from some degree of radiation-induced alopecia, which supports the conclusion that prostaglandins may be useful in the protection of hair follicles in patients treated with radiation for brain tumors. PMID- 1587755 TI - Differences in radiation response between cells in S-phase and non-S-phase cells of the granulocyte/macrophage progenitor (GM-CFC) compartment. AB - Studies were performed to investigate the radiation response of granulocyte/macrophage progenitor cells from canine bone marrow in different proliferative states, and in which way it will change if the S-phase cells are eliminated from the irradiated populations. To obtain progenitor cells of different proliferative states, bone marrow cell suspensions were kept in liquid cultures for 1 or 3 days in the presence of colony stimulating activity. Radiation dose response curves were determined (a) for the total population of progenitor cells under normal conditions (fraction of cells in S-phase 35%), (b) in a state of rapid cycling (fraction of S-phase cells 53% to 57%), and (c) after sterilization of S-phase cells by pretreatment with 3H-thymidine. The rapidly proliferating progenitor cells showed a strong decrease in their radiosensitivity (D0 = 0.84 Gy) within the first day in suspension culture when compared to the normal population (D0 = 0.50 Gy). The cell populations from which the S-phase cells had been eliminated were found more sensitive than the respective total populations (D0 values in the range from 0.44 Gy to 0.50 Gy). The D0 values for the S-phase cells were between 0.57 Gy and 1.13 Gy depending on the proliferative state of the cell populations. These data indicate that granulocyte/macrophage progenitor cells during progression through the S-phase become less radiosensitive than they are in other phases of the cell cycle. PMID- 1587756 TI - Effects of 5'-iododeoxyuridine on the repair of radiation induced potentially lethal damage interphase chromatin breaks and DNA double strand breaks in Chinese hamster ovary cells. AB - The effect of 5'-iododeoxyuridine incorporation into DNA on radiation sensitivity, cellular repair capability, induction and repair of interphase chromatin breaks, as well as induction and repair of DNA double strand breaks was investigated in plateau-phase Chinese hamster ovary cells exposed to X rays. Repair of potentially lethal damage, as measured by delayed plating plateau-phase cells, was used to assay cellular repair capacity. Induction and repair of interphase chromatin breaks were assayed by means of premature chromosome condensation, whereas induction and repair of DNA double strand breaks were assayed by pulsed field gel electrophoresis. Incorporation of 5'-iododeoxyuridine into DNA sensitized cells to radiation. Radiosensitization increased with increasing percent thymidine replacement and was accompanied by an increase in the number of chromatin breaks scored per Gy and a small increase in the number of DNA double strand breaks produced. Cells grown in the presence of 5' iododeoxyuridine were able to repair potentially lethal damage. When the comparison was made at equal doses, the extent of this repair was higher but its rate slower in 5'-iododeoxyuridine containing cells. At equal survival levels, cells that had incorporated IdU also repaired PLD to a slightly higher extent than control cells grown in IdU free medium. The magnitude of potentially lethal damage repair increased as cells "aged" in the plateau-phase, particularly for high 5'-iododeoxyuridine concentrations (8 microM). Incorporation of 5' iododeoxyuridine reduced the rate of repair of interphase chromatin breaks and the rate of repair of DNA double strand breaks (both the fast and the slow component). The results suggest that reduction in the efficiency of repair of DNA double strand breaks and chromatin breaks, produced by radiation in 5' iododeoxyuridine containing cells, is one determinant of the radiosensitization observed. PMID- 1587757 TI - Enhancement of tumor radiosensitivity and reduced hypoxia-dependent binding of a 2-nitroimidazole with normobaric oxygen and carbogen: a therapeutic comparison with skin and kidneys. AB - To evaluate the therapeutic potential of normobaric oxygen and carbogen as hypoxic-cell sensitizers, both radiosensitization in a mouse mammary carcinoma, mouse skin and kidneys, and the reduction in the proportion of hypoxic tumor cells were quantified in mice breathing air, oxygen, or carbogen. Local tumor control, acute skin reactions, reduced renal clearance, and hematocrit were used as assays. X rays as 10 fractions in 5 days were given to skin and tumors and 10F/12 days to kidneys. In the tumor study, the pre-irradiation breathing time was varied from 2 to 20 min. Hypoxic cells, before and during a 10F/5 day schedule, were quantified using a 2-nitroimidazole with a theophylline side chain. Bioreductively reduced metabolites of this probe were localized in hypoxic cells that were then stained using an immunofluorescent technique and analyzed by flow cytometry. The fraction of cells with high fluorescence intensity was 19% in air, 9% in oxygen, and 3% in carbogen-breathing mice. For all three gases, hypoxia-dependent binding was similar in non-irradiated tumors and those treated with four or nine fractions. Both gases significantly enhanced tumor radiosensitivity (ER = 1.3 to 1.6) and carbogen was slightly more effective than oxygen. With carbogen, maximum sensitization was observed with a 5 min pre irradiation breathing interval. With oxygen, pre-irradiation breathing times of 2 20 min gave similar sensitization. In skin an enhancement ratio of 1.2 was observed, whereas enhancement ratios for both renal endpoints were significantly lower (1.0 to 1.07). Relative to both tissues, there was therefore a substantial therapeutic gain by irradiating CaNT tumors under both gases, especially with carbogen. PMID- 1587758 TI - Beam's eye view volumetrics: an aid in rapid treatment plan development and evaluation. AB - A well-designed treatment plan fully irradiates the target to the prescribed dose while minimizing radiation to adjacent critical structures. Beam's eye view is an important component of treatment planning systems because it provides the operator with tools needed to achieve this goal. Through interactive manipulation of displays, the planner uses beam's eye view to adequately cover the target volume while geometrically avoiding certain critical, normal structures. A factor not considered in current beam's eye view programs is the fractional volume of each structure irradiated given a specified beam direction. We have incorporated a rapid volume calculation capability in our beam's eye view program, and have applied it to provide a quantitative aid to treatment planning development and evaluation. Treatment planning of lung tumors has been studied using this tool. Volumes of lung and spinal cord treated as a function of portal angle may be calculated much more rapidly than dose volume histograms and yet provide quantitative indices which follow the trends of dose volume histograms as a function of field angle. Plots of normal tissue volume irradiated as a function of field angle identify the optimal angle to minimize irradiated volume of a structure at a glance. For multiple field plans, a bitmap approach identifies areas treated by various combinations of beams. Volumetrics combined with beam's eye view are useful in treatment planning because they (a) provide quantitative information needed in choosing and optimizing portal entry angle (b) provide an interactive approach to understanding the relative merits of different multiple field plans and (c) complement the information provided by the more time consuming generation of dose volume histograms. The clinical application of this tool in treatment planning is presented. PMID- 1587759 TI - Use of nitroprusside to increase tissue temperature during local hyperthermia in normal and tumor-bearing dogs. AB - The present study investigates the effects of nitroprusside, a potent vasodilating agent, on tissue temperature during local hyperthermia in five normal and five tumor-bearing dogs. Caudal thigh muscles were heated in normal dogs and muscle temperatures were recorded during hyperthermia. Tumor-bearing dogs received two hyperthermia treatments during a course of radiation therapy. Temperatures were recorded in tumor and surrounding normal tissues. Mean arterial pressure was decreased by approximately 40-45% during nitroprusside infusion and was associated with a compensatory increase in heart rate and increases in tissue temperature. In normal dogs, muscle temperatures increased an average of 1.7 degrees C with nitroprusside administration. When nitroprusside was administered at the beginning of local hyperthermia to induce step-down heating, approximately 48% of the measured positions in caudal thigh muscle achieved a temperature greater than or equal to 43 degrees C, sufficient to induce step-down heating, during the hyperthermia episode. In tumor-bearing dogs, there was a significant increase in tumor and normal tissue temperatures during nitroprusside administration. Estimated T90 and T50 descriptors increased by 0.9 degrees C and 1.6 degrees C, respectively, for tumor tissue and by 0.4 degrees C and 1.2 degrees C, respectively, for normal tissue. Despite the increase in normal tissue temperatures no toxicity was observed in these dogs. Nitroprusside may be a useful agent for manipulation of tumor temperatures during the entire hyperthermia treatment or for a short time period at the initiation of treatment to induce step-down heating. PMID- 1587760 TI - Phase I/II trial of pre-operative radiation therapy and coloanal anastomosis in distal invasive resectable rectal cancer. AB - A total of 22 patients with the diagnosis of invasive, resectable, primary adenocarcinoma of the rectum limited to the pelvis were enrolled on a Phase I/II trial of pre-operative radiation therapy+low anterior resection/coloanal anastomosis. By pre-operative assessment, all patients had invasive tumors involving the distal half of the rectum and required an abdominoperineal resection. The median tumor size was 4 cm (1.5-6 cm) and the median distance from the anal verge was 4 cm (3-7 cm). The whole pelvis received 4680 cGy followed by a 360 cGy boost to the primary tumor bed. The median follow-up was 29 months (10 60 months). Of the 21 patients who underwent resection, 10% had a complete pathologic response and 90% were able to successfully undergo a low anterior resection/coloanal anastomosis. The incidence of local failure as a component of failure was crude: 23% and 4-year actuarial: 32%. The 4-year actuarial survival was 61%. No patients experienced Grade 3 or 4 toxicity while receiving radiation therapy, and 6% developed a partial disruption of the anastomosis. Of the patients who underwent a low anterior resection/coloanal anastomosis, 89% had a good or excellent functional result. This technique may be an alternative to an abdominoperineal resection in selected patients. Further follow-up is needed in order to determine if this approach ultimately has similar local control and survival rates as an abdominoperineal resection. PMID- 1587761 TI - Hyperfractionation in advanced carcinoma of the uterine cervix: a preliminary report. AB - Experience with twice-a-day radiation therapy program for carcinoma of the uterine cervix (FIGO Stages IIB, IIIA & IIIB) is presented. The program consists of delivering 120 cGy per fraction, two fractions a day with 6 hours between fractions. A total of 6000 cGy was delivered in 50 fractions over 5 weeks. A control group was given conventional fractionation 5000 cGy in 25 fractions, 200 cGy per fraction over 5 weeks. This feasibility study enrolled 30 patients, 15 in each group. Normal tissue reactions in skin, mucosa and bowel were recorded. The acute normal tissue reactions were enhanced in the hyperfractionation group. This was significant with regard to the bowel complications. The tumor control rate did not show any significant difference between the two groups. A short follow-up period has revealed complete healing of all acute normal tissue reactions. This study shows that further dose escalation is feasible and a study with large sample size and longer follow-up is required to reach definite conclusions. PMID- 1587762 TI - High dose endobronchial irradiation in recurrent bronchogenic carcinoma. AB - Between November 1988 and March 1990, 24 patients with endobronchial tumors that had recurred after external beam radiation therapy were treated with high dose rate intraluminal irradiation. A remote afterloading high dose rate unit was used, and most patients received two endobronchial treatments, separated by a two week interval. All patients were given the same dose and dose specification to assess the feasibility and complications of the therapy. At each treatment, 15 Gy were delivered with dose specified at a radius of 6 mm from the center of the source, which corresponds to a dose of 9 Gy at a radius of 1 cm. Overall, 21 of 24 patients (88%) showed good symptomatic improvement. Of 18 patients whose chest x-ray showed evidence of collapse or atelectasis caused by tumor obstruction, 15 (83%) had evidence of reaeration. The median duration of palliation, marked by symptoms or a chest x-ray that worsened, was 26 weeks, the range varying from seven to 40 weeks. No patient died as a result of therapy and only one had a complication, bronchospasm, which responded well to bronchodilators. One patient died of hemoptysis approximately three months after treatment. Five additional patients, who were treated off protocol because they had an Eastern Cooperative Oncology Group performance status of greater than two, also received endobronchial irradiation. All five died within one month from worsening pulmonary disease, and we do not recommend endobronchial irradiation for patients with an Eastern Cooperative Oncology Group performance status of greater than two. We conclude that high dose rate endobronchial brachytherapy effectively relieves the symptoms of endobronchial obstruction due to recurrent lung cancer and can be given safely as an outpatient procedure. As the complications were minimal in this series treated with a uniform dose of 15 Gy per treatment, future studies should aim at determining the maximum tolerated dose. This technique may also be helpful as a boost after maximal external beam irradiation or to open up areas of atelectasis prior to external beam irradiation. PMID- 1587763 TI - Interstitial pneumonitis after hyperfractionated total body irradiation in HLA matched T-depleted bone marrow transplantation. AB - Interstitial pneumonia is one of the major causes of morbidity and mortality after bone-marrow transplantation. We here report a series of 58 patients suffering from hematological malignancies who received HLA-matched T-lymphocyte depleted bone-marrow transplants between July 1985 and January 1990. Interstitial pneumonia occurred in 7/58 patients (12%) and was fatal in six. Three different pre-bone-marrow transplantation conditioning regimens were employed. Total body irradiation was delivered according to a hyperfractionated scheme of 12 fractions given three per day 5 hr apart for 4 days. Twenty-three patients received 36 mg/Kg procarbazine, 1275 UL/Kg antithymocite globulin, 14.4 Gy hyperfractionated total body irradiation and 120 mg/Kg cyclophosphamide. Only one patient developed interstitial pneumonia, but two rejected the graft and 10 relapsed. As a consequence, the total hyperfractionated scheme was increased to 15,6 Gy, cyclophosphamide to 200 mg/Kg, antithymocite globulin to 3400 UL/Kg and procarbazine eliminated. There were three cases of interstitial pneumonia, no rejection and four relapses in the 17 patients who received this regimen. In the last 18 patients hyperfractionated total body irradiation was reduced to 15 Gy, cyclophosphamide to 100 mg/Kg, and 10 mg/Kg of the myeloablative agent thiothepa added to enhance the cytoreductive effect without significantly increasing extramedullary toxicity. Three cases of interstitial pneumonia, one relapse but no rejection were recorded. Our results demonstrate that the absence of graft versus-host disease due to T-cell depletion, and radio-chemotherapy doses and schedules used for the conditioning regimen each contributed to reducing the risk of interstitial pneumonitis. Hyperfractionated total body irradiation therefore, seems to play an important role in lowering the incidence of this complication. PMID- 1587764 TI - Radiotherapy during pregnancy for clinical stages IA-IIA Hodgkin's disease. AB - Between 1956 and 1990, 775 women were treated for Hodgkin's disease at The University of Texas M.D. Anderson Cancer Center. Of these, 25 (3.2%) were pregnant at diagnosis. Seven of these women were in the first trimester, 10 in the second, and eight in the third. Prior to treatment, three women in the third trimester had normal deliveries, and six patients in the first trimester had abortions. Sixteen patients received radiotherapy for supradiaphragmatic presentations during their pregnancies. All these patients had nodular sclerosing Hodgkin's disease: Two had clinical stage IA presentations and 14 had clinical stage IIA. In two patients radiotherapy (35 Gy) was limited to the neck, three patients were treated definitively to the neck and mediastinum (40 Gy), and 11 patients received mantle irradiation (40 Gy). Four to five half-value layers of lead were used to shield the uterus during radiotherapy. The dose to the fetus was estimated individually in nine patients, using a combination of an Alderson Rando and a water phantom. The estimated total dose to the mid-fetus ranged from 1.4 to 5.5 cGy for treatment with 6 MV photons, and from 10 to 13.6 cGy for Cobalt 60. All 16 patients subsequently delivered full-term, normal infants. Following delivery, all of the patients had further staging procedures; eight received additional treatment. Subsequently, the disease relapsed in four patients; two eventually died of Hodgkin's disease. The 10-year determinant and overall survival rates were 83% and 71%, respectively. Currently, all offspring are physically and mentally normal, and none has developed a malignancy. Radiotherapy is an appropriate initial treatment for supradiaphragmatic presentations of Hodgkin's disease during the second and third trimesters of pregnancy, provided special attention is paid to treatment and shielding techniques. The outcome for women treated with irradiation for clinical stage I and II Hodgkin's disease during pregnancy has not been shown to be adversely affected by pregnancy, and after the first 8 weeks of gestation, the risk to the fetus appears to be minimal. PMID- 1587765 TI - The objective evaluation of alternative treatment plans. III: The quantitative analysis of dose volume histograms. AB - The computer program OSCAR evaluates dose-volume histograms in a consistent way for use in 3-dimensional treatment planning. Based on a dose prescription specified by a radiation oncologist, the technique provides a quantitative and easily understood visual analysis of a proposed dose distribution. Rapid, reliable, and consistent choices can be made between alternative treatment plans, and if necessary the results of OSCAR calculations can be used to guide the design of a plan that will be closer to the required prescription. The method is well suited to use in the definition of treatment protocols. The use of OSCAR is demonstrated by applying it to the evaluation of alternative volumetric treatment plans for ca lung. The results demonstrate the importance of using corrections for inhomogeneous tissue density in the calculation of 3-dimensional dose distributions. PMID- 1587766 TI - Vertex field verification in the treatment of central nervous system neoplasms. AB - Increasing sophistication of computerized brain tumor treatment plans has enabled clinicians to devise increasingly complex field combinations to spare as much normal brain tissue as possible. These treatment plans often call for the use of a vertex field. This report describes a simple, useful technique for the verification of the vertex (or any non-coplanar) field on the treatment machine- a procedure that is impossible with conventional port film techniques. PMID- 1587768 TI - Mantle irradiation in the upright position: a technique to reduce the volume of lung irradiated in patients with bulky mediastinal Hodgkin's disease. AB - Many patients with mediastinal Hodgkin's disease radiographically show a wider horizontal width of disease in the supine or prone as compared to the upright position. Yet for most patients mantle treatment in the supine/prone position is still preferable. This position allows good patient immobilization and precise matching between the mantle and paraaortic-splenic pedicle fields that would not be possible in the sitting or upright position. Adequate blocking of the lungs and heart remains possible in the supine position since most patients do not have extensive subcarinal Hodgkin's disease. Even when more extensive disease is present, contoured blocks to protect the heart and lungs can be adjusted to protect a greater portion of normal tissues if the mediastinal nodes respond to treatment. But if sizeable mediastinal disease persists, it may be impossible to protect sufficient heart and lung. Under these circumstances, repositioning the patient upright can shift the configuration of the mass, allowing larger lung blocks to be added. We report the use of a chair to facilitate treatment with mantle irradiation in the upright position for patients whose mediastinal disease when supine is too large to allow adequate blocking of heart and lung. Blocks are made from the initial port films and daily treatment films are taken to confirm an accurate set-up. To avoid excessive dose to the spinal cord, patients who are to receive para-aortic irradiation receive a maximum of 15-20 Gy in the upright position and the remainder of the mantle is given in the supine-prone position. The use of the upright technique allows for the use of radiation in patients who would otherwise be unable to receive adequate doses due to potential lung and cardiac toxicity. PMID- 1587767 TI - Tangential breast irradiation: simple improvements. AB - A series of studies using phantom and in vivo dosimetry measurements with diodes and thermoluminescent dosimetry were undertaken to establish whether simple methods are available to obtain improvements in homogeneity of dose in the treated breast, and reductions of dose to tissues outside it, when using tangential 6MV photon fields. These studies confirmed that the use of an appropriate lung density correction factor in the planning process is likely to cause a reduction in the amount of wedge compensation predicted to be necessary to produce reasonable dose homogeneity in the central axis of the beam. This was shown to be of value in eliminating potential areas of overdosage in the chest wall medial and lateral to the breast mound, and also in reducing unwanted doses to the contralateral breast and lung. Further reductions in dose to contralateral breast were confirmed to occur when the majority, or all, of the wedge compensation predicted necessary is placed on the lateral field and when the lateral tangential field is angled anteriorly in such a way as to align the posterior beam edges. Skin does above, below, and over the breast mound were observed to depend critically upon angle of incidence of the beam, with its consequent effect upon electron build-up, and the position of the breast contour in the beam. Skin doses above and below the breast mound were shown to exceed over the mound itself. This differential effect was observed to increase with increasing wedge compensation. In some situations skin doses below the breast mound nearly reached prescribed dose within the breast. The design and use of simple lead attenuators to reduce these areas of high dosage is discussed. PMID- 1587769 TI - Sagittal magnetic resonance imaging in the design of lateral radiation treatment portals for patients with locally advanced squamous cancer of the cervix. AB - Twenty-five patients with FIGO clinical Stages IB-IVA squamous cancers of the uterine cervix underwent pelvic magnetic resonance imaging to assist in the design of radiation therapy portals. Magnetic resonance imaging was used primarily to define the treatment volume required to encompass the primary disease and its direct regional extensions, and only secondarily to assess the presence or absence of lymph node metastases. The sagittal scans revealed that use of "conventional" or "standard" lateral radiation portals would have resulted in a failure to encompass all gross cancer extensions (marginal miss) in 6 patients (24%). The beam edge of standard portals would have traversed tissue within 1 cm or less of gross cancer in an additional 8 patients (32%), increasing the risk of regional underdosage of subclinical disease extensions. Use of conventional lateral portals would have resulted in incomplete coverage of the uterine fundus in 15 of 24 patients (62.5%), of whom 3 had gross cancer extension to involve the uterine cavity or the myometrium of the lower uterine segment. Conventional lateral portal design, as described and illustrated in standard radiation oncology texts, may be suboptimal for a significant percentage of patients with locally advanced or bulky cervical cancer, and could be a contributing cause of failure to control pelvic disease. Design of lateral treatment portals should be based on imaging the morbid anatomy in the treatment position, rather than on an assumption of normal anatomic relationships. PMID- 1587770 TI - Trends in the clinical management of nasopharyngeal carcinoma. PMID- 1587771 TI - The treatment of local-regional recurrence of carcinoma of the breast after mastectomy. PMID- 1587772 TI - High energy photon irradiation of the olfactory mucosa in humans. PMID- 1587773 TI - One versus two or more brachytherapy applications in cervical cancer. PMID- 1587774 TI - Interstitial implantation for base of tongue carcinoma. PMID- 1587775 TI - Ecological transition: using Bronfenbrenner's model to study sexual identity change. AB - Bronfenbrenner's (1979) ecological transition model provides a framework to study coming out in lesbians. The model takes into account activities such as sexual behavior, perceptions of the behavior, and social context in which behavior takes place. The importance of context makes this model useful in identifying possible connections between sexual identity alterations and larger social forces. Interventions based on this framework can reduce stress and promote health during coming out. PMID- 1587776 TI - Lesbian stereotypes. AB - The American Psychological Association's Committee on Gay and Lesbian Concerns (Herek, 1987) expressed a need for research that focuses specifically on the concerns of lesbians. To this end, we attempted to identify stereotypes about lesbians, as noted in 278 female nursing students' responses to open-ended questions. Content analysis of the responses revealed a number of consistent themes or stereotypes. The most prevalent stereotypes included lesbians' seduction of heterosexual women, lesbian "boasting," and the "masculine aura" of lesbians. None of the participant variables (age, educational level, social class, and type of nursing education) were significantly related to particular stereotypes. The impact of stereotypes on the acceptance of lesbians within society is discussed. PMID- 1587777 TI - Reasons American lesbians fail to seek traditional health care. AB - What reasons do lesbians have for not seeking health care? From three women's cultural events in 1990, a convenience sample was formed of 503 women (78% of whom were lesbians) who volunteered to complete a pretested qualitative and quantitative instrument. The reasons given for not seeking health care from traditional sources were that (a) low-cost, natural, or alternative care is not provided; (b) holistic care is not provided; (c) little preventive care and education are provided; (d) communication and respect are lacking; and (e) there are few women-managed clinics. PMID- 1587778 TI - Lesbians as an invisible minority in the health services arena. AB - Ten self-identified lesbians were interviewed about their health care experiences. Analysis of the data from a grounded theory approach revealed four issues: health care providers' assumption of heterosexuality, reactions to coming out, lesbians' expectations of health care, and health-care-seeking behavior. It is the invisibility of lesbians in society that lends to the continued negative experiences lesbians relate. As health care professionals, we must assess our present practices and seek ways to improve the quality of care we offer to lesbians. Some recommendations for improving care to the lesbian community are made. PMID- 1587779 TI - Health life-styles of lesbian and heterosexual women. AB - In this exploratory descriptive study, lesbian and heterosexual women's health life-style activities and health histories were investigated. Distribution of 200 written questionnaires by nonprobability snowball sampling obtained a sample of 79 heterosexual and lesbian women. The sample was predominantly white, middle class, and college educated. Responses to questions about participation in mental health counseling, birth control use, and pregnancy history showed significant differences between the groups. Likert scale questions were used to identify degree of participation in various health life-style activities. Alternative diet, use of meditation/relaxation techniques, and recreational drug use had significantly higher means in the lesbian group. Fulfilling family obligations, regular Pap testing, and use of prescription drugs were significantly higher among the heterosexual group. This study represents the author's initial exploration of lesbian health life-styles and describes similarities and differences in the health life-styles of lesbian and heterosexual women. PMID- 1587780 TI - Caring for lesbians in a homophobic society. AB - Lesbians and gays have suffered for centuries from stigmatization by homophobic, heterosexual people in Western society. It is critical for health care providers to have an understanding of alternative life-styles and the unique health concerns of homosexual people in order to provide sensitive and knowledgeable health care. Lesbian health issues such as assessing the sexual orientation of lesbians, parenting issues, lesbian battering, and the older lesbian woman are discussed. My intent in writing this article is to increase the sensitivity, knowledge, and awareness of health care providers caring for lesbians in a homophobic society. PMID- 1587781 TI - An exploration of lesbians' images of recovery from alcohol problems. AB - The author's purposes in this article are to explore the images lesbians use to describe their recovery from alcohol problems and to derive from this exercise relevant implications for health care. Lesbians' experiences in recovery are particularly significant because of growing concerns about the prevalence of alcohol problems among lesbians, the vulnerability of lesbians as an aggregate, and the cultural trend away from substance use in lesbian communities. Images of recovery are the descriptions that people offer about their healing from alcohol problems. They are the frameworks by which problem drinkers interpret the meanings of their experiences and determine which aspects of their lives are most pertinent to their recovery efforts. The images persons use to represent their progress and the difficulties they encounter in recovery also provide important bases for developing relevant resources, therapeutic techniques, and social support. Excerpts from an ongoing ethnographic interview study about the recovery experiences of lesbians with alcohol problems illustrate the diversity of recovery images that are characteristic of this population. PMID- 1587782 TI - How do lesbian women develop serenity? AB - This article considers how lesbian women recover from alcoholism and develop serenity in the context of a homophobic society. We review what is known about the incidence and lethality of alcoholism in lesbian women. We critique Finnegan and McNally's (1987) five-stage conceptual framework of lesbian and alcoholic identity development, which is based on the disease model of recovery. We present our own model, based on our own recovery experiences. The Deevey-Wall model describes factors that may determine how shaming social environments may affect drinking behavior and recovery in lesbian women. In conclusion, we explain Wall's theory of self-hate as a survival mechanism in traumatically hostile environments. PMID- 1587783 TI - Lesbian childbearing couples' dilemmas and decisions. AB - In recent years, an increasing number of lesbian women have chosen to bear children. However, for lesbians, there are many obstacles and unique dilemmas during each phase of the childbearing process. Some of these dilemmas include how to conceive, where to find a health care provider who is sensitive to their concerns, and how to inform family members and friends about the pregnancy and elicit their support. Other dilemmas common to all women are where to give birth and how to assimilate new roles into their life and work. This article describes the potential dilemmas of lesbians during childbearing, with the aim of increasing health care providers' awareness of and sensitivity to the perinatal concerns of lesbian women. PMID- 1587784 TI - An investigation of the health care preferences of the lesbian population. AB - A descriptive study was done to explore the health care preferences of 178 self identified lesbians. They were surveyed regarding their preferences for health care services, health care providers, clinic logistics, and identification and documentation of sexual preference. Holistic counseling, health maintenance, and disease prevention services were identified as their top priorities. Female health care providers were identified as a priority, and most of the women felt that sexual preference should be asked but not recorded in the chart. PMID- 1587785 TI - The lesbian custody project. AB - In the United Kingdom the backlash against feminism in the late 1980s was initially directed at lesbians and was specifically focused on lesbians who are mothers, lesbians engaged in parenting, or lesbians wishing to do so. This backlash was initially orchestrated by a small group of far right politicians, well to the right of the Thatcher government, and was not contained in any political consensus but was developed into a major public issue by the media. This paper documents its effect in terms of a systematic legal attack on lesbian parenting. The aim of the paper is to alert readers to the backlash with a view to resistance. Our argument is that the backlash against lesbians is a first line of attack against all women as mothers. PMID- 1587786 TI - Lesbian health care research: a review of the literature from 1970 to 1990. AB - The author critically examines the research about health care providers' attitudes toward lesbians and the research about lesbians' experiences in health care encounters. Results of the review suggest that caregivers hold prejudiced views of lesbians and are generally condemnatory and ignorant about their lesbian clients. Lesbians frequently interpret caregivers' behaviors as hostile and rejecting and fear for their safety in health care interactions. Upon disclosure of their lesbian identity, many have been mistreated. Because of their negative experiences, they often delay seeking health care. Rather than conditions of respect and regard, lesbians report atmospheres of intimidation and humiliation, which encumber their interactions with health care providers. Tables outlining the study foci, samples, methods, and findings are provided. Ramifications of findings are discussed, implications for practice and policy are identified, and directions for future research about lesbian health care are suggested. PMID- 1587787 TI - Lesbian health: what are the issues? PMID- 1587788 TI - A trisialoganglioside containing a sialyl alpha 2-6 N-acetylgalactosamine residue is a cholinergic-specific antigen, Chol-1 alpha. AB - Cholinergic-specific antigens termed the Chol-1 family have been suggested to be of a ganglioside nature by Richardson et al. (J. Neurochem. 38, 1605-1614, 1982). Two molecular species of polysialogangliosides among bovine brain gangliosides were found to react with anti-Chol-1 alpha antiserum. One of them, Chol-1 alpha a, was isolated and characterized as a trisialoganglioside containing the gangliotetraose backbone in which 1 mol of sialic acid was attached to each of the reducing end galactose, N-acetylgalactosamine and internal galactose residues, respectively. The chemical structure of Chol-1 alpha-a was determined for the first time, being as follows: IV3NeuAc III6NeuAc II3NeuAc-GgOse4 Cer. PMID- 1587789 TI - Changes in contractile properties with selective digestion of connectin (titin) in skinned fibers of frog skeletal muscle. AB - Changes in contractile properties of mechanically skinned fibers were examined when connectin in the fibers was selectively digested by a low concentration (0.25 microgram/ml) of trypsin. Resting tension and isometric active tension were reduced as the digestion of the connectin progressed; the rate of reduction of active tension was larger than that of resting tension. Maximum shortening speed and calcium ion sensitivity of active tension were not changed by the digestion. Electron micrographs showed that A-bands in the fibers treated with trypsin are dislocated from I-bands. These results suggest that the digestion of connectin does not directly influence the reaction of actin-myosin-regulatory proteins, and thus the resultant reduction in the active tension is mainly due to disordering of the regular structure in a sarcomere. PMID- 1587790 TI - Molecular and enzymatic properties of furin, a Kex2-like endoprotease involved in precursor cleavage at Arg-X-Lys/Arg-Arg sites. AB - We have recently shown that furin, a mammalian homologue of the yeast precursor processing endoprotease Kex2, is involved in precursor cleavage at sites marked by the Arg-X-Lys/Arg-Arg motif within the constitutive secretory pathway. In this study, we analyzed molecular and enzymatic properties of furin expressed in Chinese hamster ovary cells using gene transfer techniques. COOH-terminal truncation analyses indicate that the polypeptide region significantly conserved among the Kex2 family members is required for the endoprotease activity of furin, while the COOH-terminal unconserved region containing the Cys-rich domain and the transmembrane domain is dispensable. A mutant of furin truncated up to the transmembrane domain from the COOH-terminus was secreted into the culture medium as an active form. The sequence requirements for precursor cleavage of this truncated furin determined in vitro were similar to those of wild-type furin determined by expression studies in cultured cells. It had a strong resemblance to the Kex2 protease in the inhibitor profile and pH dependency. These observations support the notion that furin is the endogenous endoprotease involved in precursor cleavage at Arg-X-Lys/Arg-Arg sites. PMID- 1587791 TI - Structural organization and expression of the gene for bovine myosin I heavy chain. AB - Brush border myosin I heavy chain (MIHC), known previously as the brush border 110-kDa protein, contains an amino-terminal sequence which is highly homologous to the globular head domain of conventional myosin II heavy chain (MIIHC). The carboxyl-terminal sequence of MIHC completely diverges from that of MIIHC and functions as calmodulin-binding and membrane-interaction sites. In this investigation, we determined the structural organization of the bovine MIHC by isolating a set of genomic segments containing the whole MIHC gene. The bovine MIHC gene is 26 kilobase pairs long and consists of 28 exons. At the homologous amino-terminal portion of MIHC, many introns are located at positions equivalent to those of the rat MIIHC gene and the amoeba MIHC gene. At the carboxyl-terminal sequence of MIHC, the putative calmodulin-binding and membrane-interacting domains are specified by discrete sets of exons. These findings support the view that the amino-terminal head portions of MIHC and MIIHC evolved from a common ancestral origin and also that the MIHC protein was generated as a result of fusion of discrete genomic segments encoding different functional and structural protein domains. Analysis of tissue expression of the MIHC mRNA was also extended in this investigation, and the results indicated that this mRNA is expressed in some tissues other than the intestines. PMID- 1587792 TI - X-ray scattering study of the shape of the DNA region in nucleosome core particle with synchrotron radiation. AB - The structure of the DNA region in rat thymus nucleosome core particle has been studied by synchrotron X-ray scattering analysis and the contrast-variation technique has been applied to determine the contribution of the DNA to the total scatterings. Small-angle contrast-matching measurements show that the entire core particle and isolated histone octamers are contrast-matched by solvents containing 64 and 54% (w/w) sucrose, respectively. At a contrast of 54% sucrose, where the scattering of the DNA dominates, the scattering data extending to higher angle of about 0.05 A-1 have been collected from relatively concentrated solutions (10 mg/ml) of core particles and interpreted on the basis of the regular helical model for the DNA region. The model calculations show that the shape of the DNA around the histone core is approximately by 1.8 turns of regular helix of 42 A radius and 28 A pitch. These values for helical parameters of our model are in good agreement with those of the structure of DNA in crystallized nucleosome cores shown by earlier diffraction studies. PMID- 1587793 TI - Characterization of a unique nonsecretory ribonuclease from urine of pregnant women. AB - We have reported previously [Sakakibara, et al. (1991) Chem. Pharm. Bull. 39, 146 149] that a protein purified from a partially purified pharmaceutical preparation of human chorionic gonadotropin (a urinary protein preparation from pregnant women) is a unique nonsecretory ribonuclease (RNase)-like protein on the basis of its amino terminal sequence homology. We purified the protein further from the same materials by gel filtration and reversed-phase column chromatographies with RNase activity as an index. The purified protein was designated RNase UpI-2. The catalytic activity and its sensitivity to inhibition by divalent cations suggest that the protein is related to nonsecretory RNase. The estimated molecular weight of RNase UpI-2 (38 kDa) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was significantly higher than that of urinary nonsecretory RNases (13 to 19 kDa) reported so far. After trifluoromethanesulfonic acid treatment, the molecular weight of RNase UpI-2 was reduced and approached that of nonsecretory RNase, which indicated that the protein contains a significant amount of carbohydrate (approximately 50%). RNase UpI-2 was immunoreactive with antibodies to a nonsecretory RNase, RNAase 1 [Yasuda et al. (1988) Biochim. Biophys. Acta 965, 185-194]. By immunoblot analysis of the protein freshly prepared from various urine samples, it was shown that a considerable amount of RNase UpI-2 is present in urine of pregnant women, but only a trace of RNase UpI 2, if any, was detected in urine of nonpregnant women and men. These results suggest the possibility that RNase UpI-2 may have been formed via a specific protein modification in pregnant women. PMID- 1587794 TI - Molecular cloning and expression of cDNA encoding a galactose/N acetylgalactosamine-specific lectin on mouse tumoricidal macrophages. AB - We previously reported that the mouse macrophage galacose and N acetylgalactosamine-specific lectin (MMGL) may participate in the binding of the macrophages to tumor cells [Oda, S., Sato, M., Toyoshima, S., & Osawa, T. (1989) J. Biochem. 105, 1040-1043]. We now report the cloning and characterization of a cDNA encoding MMGL. The MMGL gene encoded a protein consisting of 304 amino acid residues with a molecular weight of 34,595. The deduced amino acid sequence indicated that MMGL had a single membrane-spanning region, three leucine zipper like domains, and a carbohydrate recognition domain. Two N-glycosylation sites were found in the extracellular region of MMGL, corresponding to the heavy N glycosylation in the native MMGL. Comparison of the amino acid sequence of MMGL with those of rat hepatic lectins revealed a high overall sequence homology. The sequence homology was especially high in the putative membrane-spanning region and carbohydrate recognition domain. There was, however, a region of 25 amino acids which did not exist on hepatic lectins. The MMGL cDNA without the region encoding the putative membrane-spanning region and intracellular region was expressed in Escherichia coli. The expressed protein had galactose-binding activity and its sugar-binding specificity was same as that of the native lectin. PMID- 1587795 TI - Non-acid glycosphingolipid expression in plasma of an A1 Le(a-b+) secretor human individual: identification of an ALeb heptaglycosylceramide as major blood group component. AB - Total non-acid glycosphingolipids were isolated from plasma of an A1 Le(a-b+) secretor individual with Refsum's disease (phytanic acid storage disease). The glycolipids were separated into 11 fractions by open column chromatography and by HPLC. The fractions were analyzed by thin-layer chromatography and tested for different blood group A activities as well as blood group Le(a )and Leb activity. The fractions were structurally characterized by proton NMR spectroscopy and FAB mass spectrometry and in selected cases by EI mass spectrometry of the permethylated and permethylated-reduced derivatives. Degradation analysis was performed on partially permethylated or permethylated-reduced alditol acetates. The dominating blood group compound was found to be a blood group A active type 1 chain difucosylheptaglycosylceramide. Other blood group compounds were identified as a blood group A active type 1 chain monofucosylhexaglycosylceramide, a blood group Leb hexaglycosylceramide, a blood group H active type 1 chain pentaglycosylceramide, and a globotetraosylceramide (the P-antigen). The presence of a Le(a) glycosphingolipid and blood group A type 3/4 chain structures were also found by immunostaining. Glucosyl-, lactosyl-, and globotriaosylceramides were the dominating short chain compounds. The amount of phytanic acid incorporated into the monoglycosylceramide fraction was found to be less than 5% of the fatty acids. PMID- 1587797 TI - A dominant mutation that alters the regulation of INO1 expression in Saccharomyces cerevisiae. AB - A dominant, single nuclear gene mutation, CSE1, caused inositol auxotrophy in yeast cells. The inositol requirement was marked when choline was present in the medium. Inositol-1-phosphate synthase, the regulatory enzyme of inositol synthesis, is repressed by inositol, or more profoundly by a combination of inositol and choline in the wild type. In CSE1, the level of inositol-1-phosphate synthase was low and was greatly repressed on the addition of choline alone. In accordance with this, INO1 mRNA encoding the enzyme was low even under the depressed conditions and was profoundly decreased by choline in CSE1. But in the wild type, the addition of choline alone had little effect. An INO1-lacZ fusion was constructed and the control of the INO1 promoter in CSE1 was studied. lacZ expression was repressed not only by inositol, but also by choline in CSE1, whereas it was repressed by inositol, but only slightly by choline in the wild type. CSE1 was unlinked to the INO1 structural gene. Thus CSE1 was thought to be a regulatory mutation. Furthermore, when the CDP-choline pathway was mutationally blocked, choline did not affect INO1 expression, indicating that the metabolism of choline via the CDP-choline pathway is required for INO1 repression. PMID- 1587796 TI - Identification and partial purification of a thiol endothelin-converting enzyme from porcine aortic endothelial cells. AB - Endothelin is a potent peptide vasoconstrictor. The final step in the processing of endothelin has been postulated to be the cleavage of the Trp21-Val22 peptide bond in proendothelin by a putative endothelin-converting enzyme. A soluble extract of primary porcine aortic endothelial cells was found to contain an enzyme activity that converted proendothelin-1 (proET-1) to an endothelin-1 (ET 1)-like peptide as determined by the rabbit aortic ring contraction assay. This enzyme was partially purified by DE52 ion-exchange chromatography. Incubation of proET-1 with the partially purified enzyme generated a product which had a retention time on HPLC identical to that of authentic ET-1. Further analysis of the product showed that it caused contraction of rabbit aortic rings, had a molecular weight identical to ET-1 as measured by fast atom bombardment mass spectrometry, and competed for [125I]ET-1 binding in an RIA using specific antibodies which recognize the carboxy terminal tryptophan of ET-1. The enzyme activity could be inhibited by thiol protease inhibitors such as Z-phe-pheCHN2 and p-hydroxymercuribenzoate, but not by serine- or metalloprotease inhibitors. The optimal pH for the enzymatic activity was between 7.0 and 7.5, and no activity was detected at pH 4.0. These results demonstrate that this thiol protease is a potential endothelin-converting enzyme. PMID- 1587798 TI - Anion-induced conformational change of apo-electron-transferring flavoprotein. AB - Apoprotein of electron-transferring flavoprotein (ETF) exists in an equilibrium between two different forms, only one of which can associate with FAD (Sato, K. et al. (1991) J. Biochem. 109, 734-740), as represented in the following kinetic scheme: A* in equilibrium with A, A+FAD in equilibrium with holoETF, where "A*" and "A" are the different forms of apoETF. In the present study, the effects of various anions on the conversion between the two forms of apoETF were investigated by kinetic analyses on binding of FAD to apoETF. All the anions tested here induced the conversion from "A*" to "A"; the order of the effectiveness was I- approximately Br- greater than Cl- greater than F-. Further, glycerol also induced the conversion from "A*" to "A". The elution pattern of apoETF on molecular sieve chromatography was changed by addition of salts or glycerol; this change was due to the conversion from "A*" to "A" by the added solutes. The "A*" form was eluted more rapidly than the "A" form, indicating that the "A*" form exists in a looser conformation than the "A" form. The far-UV CD spectral change upon addition of salts indicated that a greater part of the secondary structure is retained in the conversion from "A*" to "A," but the "A" form contains a somewhat larger amount of beta-sheet than "A*." PMID- 1587799 TI - Actin kinase: a protein kinase that phosphorylates actin of fragmin-actin complex. AB - Actin of fragmin-actin complex is phosphorylated by an endogenous kinase from plasmodium of Physarum polycephalum. The phosphorylation abolishes the nucleation and capping activities of fragmin-actin complex. The kinase has been purified and termed actin kinase [Furuhashi, K. & Hatano, S. (1990) J. Cell Biol. 111, 1081 1087]. Enzymatic properties of the purified actin kinase were studied in detail. Actin kinase exhibited the highest activity under conditions physiological for the plasmodium (30 mM KCl, 6 mM MgCl2, pH 7.0). The Vmax and the Km of the enzyme for ATP were about 83 mumol/min/mg and 25 microM, respectively. The Km for fragmin-actin complex was 190 nM. The purified actin kinase phosphorylated actin of fragmin-actin complex at a constant rate regardless of Ca2+ concentration. Similarly, 2 microM cAMP, 2 microM cGMP, 2 micrograms/ml calmodulin in the presence of Ca2+ or 1 mM GTP showed no effect on the activity of the purified enzyme. Actin kinase did not phosphorylate histone H1, H2B, alpha-casein, or beta casein, suggesting that actin kinase is a new kind of protein kinase which specifically phosphorylates actin of the fragmin-actin complex. PMID- 1587800 TI - Ubiquinone biosynthesis by mitochondria, sonicated mitochondria, and mitoplasts of rat liver. AB - Ubiquinone was biosynthesized when rat liver mitochondria were incubated with S adenosyl-L-methionine, solanesyl diphosphate, and [U-14C]p-hydroxybenzoate. The intermediates of ubiquinone biosynthesis but not ubiquinone were accumulated in mitochondria incubated without S-adenosyl-L-methionine and the accumulated intermediates were converted to ubiquinone by the addition of the methyl group donor and an excess of cold p-hydroxybenzoate. No solaneylated compounds except nonaprenyl p-hydroxybenzoate were found in sonicated mitochondria, while the biosynthesis of ubiquinone was observed in the sonicated preparation of mitochondria in which the intermediates accumulated. The results indicate that the initial decarboxylation reaction is completely abolished and the subsequent reactions of hydroxylation and methylation are not completely inhibited by the sonication treatment and therefore the decarboxylation reaction is the next step after nonaprenylation of p-hydroxybenzoate. Mitoplasts could biosynthesize ubiquinone with activity comparable to that of intact mitochondria, suggesting that components of the outer membrane and the intermembranous space of mitochondria are not involved in ubiquinone biosynthesis. PMID- 1587801 TI - A 13C NMR study on collagens in the solid state: hydration/dehydration-induced conformational change of collagen and detection of internal motions. AB - We recorded 13C NMR spectra of type I and IV collagens in the anhydrous and hydrated states, in order to confirm our previous assignment of peaks, and to analyze the mode of partial renaturation of soluble collagens by hydration, as well as rapid intramolecular motions such as ring puckering in proline or hydroxyproline residues. First, we attempted to assign all 13C NMR peaks of collagen fibrils on the basis of computer simulation by utilizing amino-acid composition and chemical shift data from both the solid state and solution. We confirmed that some previously unassigned peaks were not ascribable to a denatured portion but to the minor amino-acid residues. The 13C NMR peaks from soluble collagens were appreciably broadened and some peaks were displaced as compared with those of intact collagen fibrils. This was caused by the presence of a partial conformational disorder and/or denaturation at the time of acid solubilization and dehydration. Those line broadening and displacements of peaks, however, were partially removed by humidification under an atmosphere of 96% R.H. over 12 h. Furthermore, we found that the 13C spin-lattice relaxation times (T1s) of both the C beta and C gamma carbons of Pro and Hyp in fibrils are substantially reduced as compared with those of some crystalline oligopeptides. It was shown that the presence of rapid ring puckering motion in these residues results in a reduction of the NT1 values, where N stands for the number of protons attached to the carbon under consideration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587802 TI - Carbohydrate binding specificity of monoclonal antibodies raised against lactose protein Maillard adducts. AB - Three hybridoma antibodies (L101, L104, and L117) specific for lactose-protein amino carbonyl products (Maillard adducts) were obtained by immunizing mice with the lactose-ovalbumin Maillard adduct and by screening with the lactose-bovine serum albumin (BSA) adduct. They reacted with the Maillard adducts of lactose with several different proteins, but not with the adducts of several other reducing sugars. L101 reacted well with the lactose-BSA adducts formed by 2- to 16-day incubation, whereas L104 and L117 reacted with the advanced stage reaction products but not with the adducts of 2-day incubation. The competitive inhibition of the antibody binding by several mono- and disaccharides showed that lactulose (4-O-beta-D-galactopylanosyl-D-fructose) was the best inhibitor for all three antibodies, and that L104 and L117 were inhibited by methyl-beta-D-galactoside more effectively than L101. These results suggested that different components produced during the progress of the Maillard reaction could be antigenic determinants, and that the carbohydrate moiety including the terminal galactosyl residue played an important role in the antibody binding to the lactose-protein Maillard adducts. PMID- 1587803 TI - Structures of sugar chains of the subunits of an alpha-amylase inhibitor from Phaseolus vulgaris white kidney beans. AB - The structures of asparagine-linked oligosaccharides in the subunits of an alpha amylase inhibitor from the white kidney bean (Phaseolus vulgaris) were determined. Glycopeptides obtained from each subunit were treated with hydrazine, then N-acetylated. The oligosaccharides thus liberated were labeled with 2 aminopyridine at their reducing ends and purified by gel-permeation, reverse phase, and size-fractionation HPLC. The structures of seven oligosaccharides from the alpha-subunit and eight oligosaccharides from the beta-subunit were determined by a combination of composition and molecular size analyses, exo- and endoglycosidase digestions, partial acetolysis, and 1H-NMR spectroscopy. The major glycan chains in the alpha-subunit were Man alpha 1-6(Man alpha 1-3)Man alpha 1-6(Man alpha 1-2Man alpha 1-3)-Man beta 1-4GlcNAc beta 1-4GlcNAc and (Man alpha 1-2)Man alpha 1-6(Man alpha 1-2Man alpha 1-3)Man alpha 1-6 (Man alpha 1 2Man alpha 1-2Man alpha 1-3)Man beta 1-4GlcNAc beta 1-4GlcNAc, while a glycan chain Man alpha 1-6(Man alpha 1-3)(Xyl beta 1-2)Man beta 1-4GlcNAc beta 1-4GlcNAc comprised more than 70% of the sugar moiety of the beta-subunit. PMID- 1587804 TI - Characterization of carbohydrate-binding specificity of concanavalin A by competitive binding of pyridylamino sugar chains. AB - Carbohydrate-binding specificity of Con A was characterized by competitive binding studies of pyridylamino (PA) sugar chains. PA-derivatives of 17 oligomannose-type sugar chains, Man1-9GlcNAc2-PA, and those of three complex-type sugar chains were used as ligands. The ratios of bound and free sugar concentrations, [LS]/[S], were determined by means of microequilibrium dialysis followed by high performance liquid chromatography as already reported [Mega, T. & Hase, S. (1991) J. Biochem. 109, 600-603]. The association constant, Ka, was calculated from [LS]/[S] of a sugar chain and that of a standard sugar chain by using the equation Ka = Ka0 x ([S0]/[LS0]) x ([LS]/[S]), where Ka0, [S0], and [LS0] are the association constant, and the free and bound ligand concentrations of the standard sugar chain, respectively. This calculation was effective for the determination of Ka of ligands with similar affinities to the standard sugar chain. The carbohydrate structures with highest affinity for Con A among those tested were found to be: [formula: see text] PMID- 1587805 TI - Modulation of active renin secretion by renin-binding protein (RnBP) in mouse pituitary AtT-20 cells transfected with human renin and RnBP cDNAs. AB - To investigate the role of renin-binding protein (RnBP) in renin metabolism, RnBP expression plasmid, which was constructed to express human RnBP under the control of mouse mammary tumor virus long terminal repeat, was transfected into mouse pituitary AtT-20 cells together with the expression plasmid encoding human renin. The transfectant secreted prorenin and active renin, whereas RnBP was expressed only in the presence of dexamethasone and without secretion into the medium. The secretion of active renin was stimulated by forskolin, and the stimulation was repressed by dexamethasone. The secretion of prorenin, however, was insensitive to forskolin irrespective of the presence or absence of dexamethasone. Moreover, the forskolin-stimulated release of active renin was hardly repressed by dexamethasone in AtT-20 cells transfected with the renin expression plasmid and a selectable plasmid pMAMneo. Coexistence of RnBP and renin mRNAs in human Wilms' tumor G-401 cells was shown by means of polymerase chain reaction of respective cDNAs from the cells. These results suggest that RnBP modulates the release of active renin in renin-producing cells. PMID- 1587806 TI - Interaction of rat lecithin-cholesterol acyltransferase with rat apolipoprotein A I and with lecithin-cholesterol vesicles. AB - The interaction of rat plasma lecithin-cholesterol acyltransferase with lecithin cholesterol vesicles and with rat apo-A-I was studied in comparison with that of human plasma lecithin-cholesterol acyltransferase to clarify the reaction mechanism of rat plasma lecithin-cholesterol acyltransferase. The interaction of both human and rat lecithin-cholesterol acyltransferase with lecithin-cholesterol vesicles was investigated by gel permeation chromatography on Superose 12. Both enzymes had almost the same affinity to the vesicles. The affinity of rat enzyme to rat apo-A-I was stronger than that of human enzyme to human apo-A-I when estimated on the apo-A-I-Sepharose 4B column. When human apo-A-I was added to the human enzyme/vesicle mixture which contained the enzyme-vesicle complex, the enzyme was effectively dissociated from the complex. But when rat apo-A-I was added to the rat enzyme/vesicle mixture, apo-A-I-enzyme-vesicle complex was still recognized by its elution pattern on gel permeation chromatography. This suggests that the mixture of rat enzyme, rat apo-A-I, and vesicles, which are the major components in the rat lecithin-cholesterol acyltransferase reaction, forms a stronger complex than do the components of the human reaction. PMID- 1587807 TI - A decrease of lipid fluidity of the porcine intestinal brush-border membranes by treatment with malondialdehyde. AB - The effect of treatment of the porcine intestinal brush-border membranes with malondialdehyde (MDA) on their lipid fluidity was examined using a fluorescence probe, 1,6-diphenyl-1,3,5-hexatriene (DPH). When the membranes were treated with MDA, the fluorescence anisotropy of DPH-labeled membranes increased and the amount of DPH molecules incorporated into the membranes decreased from 3.25 to 2.23 nmol/mg protein. In addition, the response of the fluorescence anisotropy of DPH-labeled membranes to benzyl alcohol, a well-known fluidizer, was markedly suppressed by treatment of the membranes with MDA. These results suggest that treatment of the membranes with MDA causes a decrease of the membrane lipid fluidity. This interpretation was further supported by the increase observed in the fluorescence anisotropy of DPH-labeled liposomes prepared from the extracted lipids of MDA-treated membranes. The results of SDS-polyacrylamide gel electrophoresis suggested that the formation of high-molecular-weight aggregates of the membrane proteins is not involved in the increase of the fluorescence anisotropy of DPH-labeled membranes by treatment with MDA. On the basis of these results, changes in the physical properties of the intestinal brush-border membranes by treatment with MDA are discussed. PMID- 1587808 TI - The pterin molybdenum cofactors. PMID- 1587809 TI - Expression of the GTPase activating domain of the neurofibromatosis type 1 (NF1) gene in Escherichia coli and role of the conserved lysine residue. AB - A small catalytic domain from the neurofibromatosis type 1 gene, NF1-333, consisting of 333 amino acids between residues 1197 and 1528, including an additional N-terminal methionine, was expressed in Escherichia coli as a soluble protein. Its catalytic activity under non-saturating conditions is similar to the full-length p120-GAP but different from truncated GAP-334. Under saturating conditions its kcat and KM are lower. Lys-1422, which is totally conserved in all GAP proteins, was mutated and the properties of the mutant protein investigated. Lys-1422 seems to be essential for the stability of the proteins and not for its catalytic activity. PMID- 1587810 TI - Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging. AB - Prolonged incubation of protein with reducing sugar proceeds through a series of reactions involving early stage products to the advanced glycation end products with fluorescence, brown color, and cross-linking. Known collectively as the Maillard reaction, these changes have been suggested as factors in diabetic complications and the aging process. The early stage products have been demonstrated in vivo, but evidence for the presence in vivo of the advanced glycation end products has been limited. We sought to provide immunochemical evidence by the preparation and use of polyclonal and monoclonal antibodies to these end products (Horiuchi, S., Araki, N., and Morino, Y. (1991) J. Biol. Chem. 266, 7329-7332) as probes to identify and quantitate such compounds in human lens crystallins. Neither of the antibodies reacted with extracts from infant lenses, but fractions from adult lenses showed a significant reactivity, correlating with lens age. Our findings provide the first immunochemical evidence that human lens crystallins contain advanced glycation end products and that these products increase with tissue age. PMID- 1587811 TI - Isolation of a gene encoding a putative leucine zipper structure that is induced by transforming growth factor beta 1 and other growth factors. AB - A gene sequence (TSC-22) that is induced by transforming growth factor (TGF) beta 1 was isolated by differential screening of a lambda gt10 cDNA library constructed from poly(A)+ RNA of mouse osteoblastic cells treated with TGF-beta 1 for 2 h. TSC-22 gene expression was transcriptionally activated by TGF-beta 1. It was also induced by phorbol 12-myristate 13-acetate, serum, cholera toxin, or dexamethasone, but not appreciably by epidermal growth factor. Its induction was rapid and transient, reaching a peak 2 h after TGF-beta 1 treatment, and was resistant to cycloheximide like that of c-jun. The nucleotide sequences of TSC-22 cDNA showed no homology with any known gene sequence. The open reading frame and in vitro translation product indicated that the gene encodes a polypeptide of 143 amino acids with a molecular mass of 18 kDa that contains a putative leucine zipper structure. Polyclonal antibody was raised against TSC-22 protein expressed in Escherichia coli cells, and the antibody detected a 18-kDa protein in both the cytoplasmic and nuclear fractions of [35S]Met-labeled cells. These results indicate that the TSC-22 gene is a new member of the family of early response genes, and encodes a small polypeptide that is a putative transcriptional regulator. PMID- 1587812 TI - Chemical synthesis of a biotinylated derivative of the simian immunodeficiency virus protease. Purification by avidin affinity chromatography and autocatalytic activation. AB - The protease from simian immunodeficiency virus (SIV) was chemically synthesized by automated solid-phase technology as an NH2-terminally extended derivative, capped with biotin. Biotin-linker-(SIV protease (1-99)): the linker segment, Gly Gly-Asp-Arg-Gly-Phe-Ala-Ala, corresponds to the amino acid sequence preceding that of the protease in the SIV gag/pol precursor polyprotein. Accordingly, the Ala-Pro bond joining the octapeptide linker to the protease constitutes a site naturally cleaved by the protease during viral maturation. This strategy for synthesis was designed to facilitate purification of the biotinylated protein derivative from a complex mixture of reaction products by avidin/agarose-affinity chromatography and to provide the means for autocatalytic removal of the biotin linker segment. As anticipated, folding of the full-length construct leads to activation of the enzyme and excision of the desired 99-residue SIV protease (overall yield, approximately). The specificity of the synthetic SIV protease toward a number of well characterized protein substrates was the same as observed for the nearly identical enzyme from human immunodeficiency virus type 2 (HIV-2 protease) and distinct from that of the more disparate HIV-1 protease. The same functional ordering with respect to the human retroviral proteases was reflected in Ki values observed with a number of protease inhibitors. Thus, the folded synthetic SIV protease shows patterns of specificity and susceptibility to inhibition that are in accord with what would be expected based upon its degree of structural similarity to proteases from HIV-1 and HIV-2. PMID- 1587814 TI - Region-directed mutagenesis of residues surrounding the active site nucleophile in beta-glucosidase from Agrobacterium faecalis. AB - The active site nucleophile of the beta-glucosidase of Agrobacterium faecalis has recently been identified by the use of inhibitors. A combination of site-directed and in vitro enzymatic mutagenesis was carried out on the beta-glucosidase to probe the structure of the active site region. Forty-three point mutations were generated at 22 different residues in the region surrounding the active site nucleophile, Glu358. Only five positions were identified which affected enzyme activity indicating that only a few key residues are important to enzyme activity, thus the enzyme can tolerate a number of single residue changes and still function. The importance of Glu358 to enzymatic function has been confirmed and other residues important to enzyme structure or function have been identified. PMID- 1587813 TI - Kinetic analyses of the binding of leukemia inhibitory factor to receptor on cells and membranes and in detergent solution. AB - The equilibrium and kinetic properties of leukemia inhibitory factor (LIF) binding to a range of cell types have been compared. When binding was examined at 4 degrees C, the majority of cells were found to express a single class of high affinity LIF receptor (KD = 20-100 pM; ka = 2-8 x 10(8) min-1 M-1; kd = 0.0004 0.0011 min-1). In contrast, certain activated macrophage populations expressed apparently independent classes of high and low affinity LIF receptor. The low affinity receptors differed from the high affinity receptors in terms of the dissociation rate of the receptor-ligand complex (KD = 1-2 nM; ka = 3-7 x 10(8) min-1 M-1; kd = 0.30-0.67 min-1). At 37 degrees C, the interaction of LIF with its high affinity receptor was more complicated, since occupied LIF receptors were internalized more rapidly than unoccupied receptors, internalized LIF was hydrolyzed and released from the cell, and new receptors were synthesized and expressed on the cell surface. Interestingly, when membranes were prepared from cells that expressed only high affinity receptors, both high and low affinity receptors were detected, while after detergent solubilization of membranes only low affinity receptors were apparent. These results are discussed in terms of a structural model for the LIF receptor in which interaction of a low affinity binding subunit and a second nonbinding subunit is required for the generation of the high affinity receptor. PMID- 1587815 TI - Elicitors and suppressors of the defense response in tomato cells. Purification and characterization of glycopeptide elicitors and glycan suppressors generated by enzymatic cleavage of yeast invertase. AB - Cleavage of yeast invertase by alpha-chymotrypsin produced a number of small glycopeptides that were highly active as elicitors of ethylene biosynthesis and phenylalanine ammonia-lyase in suspension-cultured tomato cells. Five of these elicitors were purified and their amino acid sequence determined. They all had sequences corresponding to known sequences of yeast invertase, and all contained an asparagine known to carry a N-linked small high mannose glycan. The most active glycopeptide elicitor induced ethylene biosynthesis and phenylalanine ammonia-lyase half-maximally at a concentration of 5-10 nM. Structure-activity relationships of the peptide part were analyzed by further cleavage of a defined glycopeptide elicitor with various proteolytic enzymes. Removal of the C-terminal phenylalanine enhanced the elicitor activity, whereas removal of N-terminal arginine impaired it. A glycopeptide with the peptide part trimmed to the dipeptide arginine-asparagine was still fully active as elicitor. Glycopeptides with identical amino acid sequences were further separated into fractions differing in the oligosaccharide side chain. A given peptide had high elicitor activity when carrying a glycan with 10-12 mannosyl residues (Man10-12GlcNAc2), a 3-fold lower activity when carrying Man9GlcNAc2 and a 100-fold lower activity when carrying Man8GlcNAc2. The oligosaccharides, released by endo-beta-N acetylglucosaminidase H from the pure glycopeptide elicitors, acted as suppressors of elicitor-induced ethylene biosynthesis and phenylalanine ammonia lyase activity. A series of such oligosaccharides in the size range of Man8 13GlcNAc was purified. The structure and composition of the purified oligosaccharides corresponded to the known small high mannose glycans of yeast invertase as verified by 1H NMR spectroscopy at 600 MHz. The highest suppressor activities were obtained with the oligosaccharides containing 10-12 mannosyl residues (Man10-12GlcNAc). The oligosaccharide Man8 GlcNAc was ineffective as a suppressor. Thus, the structural requirements for the free oligosaccharides to act as efficient suppressors were the same as for the oligosaccharide side chains of the glycopeptides for high elicitor activity. We propose that the glycan suppressors bind to the same recognition site as the glycopeptide elicitors without inducing a response. PMID- 1587816 TI - Purification and characterization of an ADP-ribosyltransferase produced by Clostridium limosum. AB - We purified a novel ADP-ribosyltransferase produced by a Clostridium limosum strain isolated from a lung abscess and compared the exoenzyme with Clostridium botulinum ADP-ribosyltransferase C3. The C. limosum exoenzyme has a molecular weight of about 25,000 and a pI of 10.3. The specific activity of the ADP ribosyltransferase is 3.1 nmol/mg/min with a Km for NAD of 0.3 microM. Partial amino acid sequence analysis of the tryptic peptides revealed about 70% homology with C3. The novel exoenzyme modifies selectively the small GTP-binding proteins of the rho family in human platelet membranes presumably at the same amino acid (asparagine 41) as known for C3. Recombinant rhoA and rhoB serve as substrates for C3 and the C. limosum exoenzyme. Whereas recombinant rac1 protein is only marginally ADP-ribosylated by C3 or by the C. limosum exoenzyme in the absence of detergent, in the presence of 0.01% sodium dodecyl sulfate rac1 is modified by C3 but not by the C. limosum exoenzyme. Recombinant CDC42Hs protein is a poor substrate for C. limosum exoenzyme and is even less modified by C3. The C. limosum exoenzyme is auto-ADP-ribosylated in the presence of 0.01% sodium dodecyl sulfate by forming an ADP-ribose protein bond highly stable toward hydroxylamine. The data indicate that ADP-ribosylation of small GTP-binding proteins of the rho family is not unique to C. botulinum C3 ADP-ribosyltransferase but is also catalyzed by a C3-related exoenzyme from C. limosum. PMID- 1587817 TI - Molecular stabilization effects of interactions between anti-metatype antibodies and liganded antibody. AB - Anti-metatype antibodies have been described as antibodies which recognize ligand induced conformational changes in the antibody variable region. Additionally, anti-metatype antibodies, produced by multiple immunizations with liganded high affinity monoclonal anti-fluorescein antibody 4-4-20, enhanced the lifetime of monoclonal antibody 4-4-20-fluorescein complex. To better understand the mechanism of the delayed dissociation rate, deuterium oxide was used to probe the liganded active site. The rate and extent of deuterium oxide-mediated fluorescence enhancement of bound ligand served to monitor the conformational dynamics of the active site in the presence and absence of anti-metatype antibodies. Results showed that anti-metatype antibodies reduced the rate and extent of deuterium oxide-mediated fluorescence enhancement of 4-4-20, a single chain derivative of 4-4-20 (consisting of the variable domains and a polylinker), and idiotypically related monoclonal anti-fluorescein antibodies suggesting that anti-metatype stabilized the liganded active site. Size exclusion liquid chromatography was utilized to isolate the liganded antibody-anti-metatype complex. Liganded single chain antibody 4-4-20 was mixed with 10-fold molar excess anti-metatype Fab fragments, and a major complex eluted with an apparent M(r) 249,000. The apparent molecular weight of this complex inferred that one liganded single chain antibody was bound by five antimetatype Fab fragments. Spectral analysis confirmed these results and the characteristic delayed rate of ligand dissociation was also observed for the isolated complex. The results suggest that anti-metatype antibodies stabilize the liganded conformation by forming a large, stable, macromolecular complex. PMID- 1587819 TI - Prereplicative complexes of components of DNA polymerase III holoenzyme of Escherichia coli. AB - Stepwise reconstitution of the subunits of DNA polymerase III holoenzyme of Escherichia coli offers insights into the organization and function of this multisubunit assembly. A highly processive, holoenzyme-like activity can be generated when the gamma complex, in the presence of ATP and a primed template, activates the beta subunit to form a preinitiation complex, and this is then followed by addition of the core polymerase. Further analysis of early replicative complexes has now revealed: 1) that the gamma complex can stably bind a single-stranded DNA binding protein (SSB)-coated template, 2) that neither SSB coating of the template nor a proper primer terminus is required to form the preinitiation complex, and 3) that the gamma complex stabilizes the preinitiation complex in the presence of ATP and destabilizes it in the presence of adenosine 5'-O-(thiotriphosphate). Based on these findings, a sequence of stages can be formulated for an activation of the beta subunit that enables it to bind the template-primer and thereby interact with the core to create a processive polymerase. PMID- 1587818 TI - Purification and characterization of a DNA-binding protein activated by ionizing radiation. AB - Exposure of mammalian cells to a variety of agents leads to the activation of pre existing proteins and the induction of specific genes. We have recently described the appearance of a specific DNA-binding protein in nuclei from cells exposed to ionizing radiation (Singh, S. P., and Lavin, M. F. (1990) Mol. Cell. Biol. 10, 5279-5285). This protein is present in the cytoplasm of unperturbed cells and is apparently translocated to the nucleus in response to radiation damage. We describe here the purification and characterization of this specific DNA-binding protein. Purification involved the use of affinity chromatography employing a multimeric form of the DNA-binding motif conjugated to cyanogen bromide-activated Sepharose. Three DNA-binding species were recognized by UV-cross-linking and South-Western analysis. The major species or that with the highest affinity was approximately 70 kDa in size. DNase-1 footprint analysis revealed a single binding site in the kappa immunoglobulin gene enhancer and in a putative control sequence upstream from the c-myc gene. At salt concentrations as high as 1 M, up to 40% of the DNA-binding activity was maintained and the Kd was calculated to be 1.205 x 10(-6) M-1. Binding activity was found to be modulated by phosphorylation. Removal of phosphate groups from the protein resulted in a major loss of binding activity. It is not clear at this stage whether the factor(s) described here plays a role in transcription control or a more general DNA processing role in response to radiation damage. PMID- 1587820 TI - Identification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. AB - The structural properties of fibroblast heparan sulfate (HS) that are necessary for it to bind strongly to basic fibroblast growth factor (bFGF) have been investigated using bFGF affinity chromatography. Specific enzymic and chemical scission of HS, together with chemical N-desulfation, revealed that N-sulfate groups and iduronate-2-sulfates (IdoA(2-OSO3)) were essential for the interaction. bFGF-affinity chromatography of sulfated oligosaccharides released from HS by treatment with heparitinase led to the identification of an oligosaccharide component (oligo-H), seven disaccharides in length, with a similar affinity for bFGF as the parent molecule. Heparinase treatment of this fraction abolished the high affinity binding to bFGF. Analysis of oligo-H indicated that 74% of the disaccharide units had the structure IdoA(2-OSO3)alpha 1,4GlcNSO3; the remainder comprised N-acetylated and N-sulfated units, the majority of which were devoid of O-sulfate groups. Oligo-H was fully degraded to disaccharides by treatment with nitrous acid. These results indicate that the sequence of oligo-H is as shown below. delta GlcA beta 1,4GlcNSO3 alpha 1,4[IdoA(2-OSO3)alpha 1,4GlcNSO3]5 alpha 1, 4IdoA alpha 1,4GlcNAc Sulfated oligosaccharides of similar size but with a lower affinity for bFGF had a reduced concentration of IdoA(2-OSO3) but significant quantities of GlcNSO3(6-OSO3) and GlcNAc(6-OSO3). The data indicate a primary role for contiguous sequences of IdoA(2-OSO3)alpha 1,4GlcNSO3 in mediating the high affinity binding between fibroblast HS and bFGF. PMID- 1587821 TI - Subunit molecular mass assignment of 14,654 Da to the soluble beta-galactoside binding lectin from bovine heart muscle and demonstration of intramolecular disulfide bonding associated with oxidative inactivation. AB - The soluble dimeric beta-galactoside-binding lectin (subunit molecular mass, approximately 14 kDa) of bovine heart muscle, in common with the 14-kDa lectins of several other animal species, displays carbohydrate-binding activity when it is in the reduced state, but the purified lectin loses this activity upon oxidation. In the present study, the presence of any post-translational modification and the mechanism of the oxidative inactivation have been investigated by analyses of the reduced and oxidized forms of the purified bovine lectin by electrospray ionization-mass spectrometry (ESI-MS) and by liquid secondary ion mass spectrometry (LSIMS) of tryptic and peptic peptides. By ESI MS, the molecular mass of the reduced lectin is determined to be 14,654.6 +/- 0.9 Da, and that of the oxidized lectin is 14,649.3 +/- 1.1 Da. These masses correspond to the amino acid sequence of the protein with the cysteines having free sulfhydryl groups in the reduced state and forming disulfide bonds in the oxidized state. There is no evidence of post-translational modification in either lectin form except for monoacetylation already predicted for alanine at the blocked N-terminal end. Pronounced differences in charge distribution in the electrospray ionization mass spectra of the reduced and oxidized lectin, reflecting a change in the number of accessible protonation sites in the oxidized protein, are consistent with the protein being held in an altered conformation by covalent bonding. The results of LSIMS analyses of tryptic and peptic peptides in conjunction with Edman sequencing indicate that disulfide bonding occurs predominantly between Cys2 and Cys130, Cys16 and Cys88, and Cys42 and Cys60. There is no evidence of oxidation of Trp68. These results, taken together with observations that almost the complete polypeptide chain is necessary for the functional integrity of the carbohydrate recognition domain (Abbott, W. M., and Feizi, T. (1991) J. Biol. Chem. 266, 5552-5557) point to intramolecular disulfide bonding with a change in protein folding and conformation as the mechanism of oxidative inactivation of the purified bovine lectin. PMID- 1587822 TI - Individual molecular species of phosphatidylcholine and phosphatidylethanolamine in myelin turn over at different rates. AB - Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of the myelin membrane exhibit heterogeneity with respect to metabolic turnover rate (Miller, S. L., Benjamins, J. A., and Morell, P. (1977) J. Biol. Chem. 252, 4025-4037). To test the hypothesis that this is due to differential turnover of individual molecular species (which differ in acyl chain composition), we have examined the relative turnover of individual molecular species of myelin PC and PE. Phospholipids were labeled by injection of [2-3H]glycerol into the brains of young rats. Myelin was isolated at 1, 15, and 30 days post-injection, lipids were extracted, and phospholipid classes were separated by thin-layer chromatography. The PC and PE fractions were hydrolyzed with phospholipase C, and the resulting diacylglycerols were dinitrobenzoylated and fractionated by reverse-phase high performance liquid chromatography. The distribution of radioactivity among individual molecular species was determined. The labeled molecular species of myelin PC were 16:0 16:0, 16:0-18:0, 16:0-18:1, and 18:0-18:1, with most of the label present in 16:0 18:1 and 18:0-18:1. Changes in distribution of label with time after injection indicated that 16:0-18:1 turned over more rapidly than 18:0-18:1. The labeled molecular species of myelin PE were 18:0-20:4, 18:1-18:1, 16:0-18:1, 18:0-18:2, and 18:0-18:1. As with myelin PC, 16:0-18:1 (and 18:1-18:1) turned over more rapidly than 18:0-18:1. The relative turnover of individual molecular species of PC in the microsomal fraction from forebrain was also examined. The molecular species profile was different from myelin PC, but again, 16:0-18:1 turned over more rapidly than the other molecular species. Thus, within the same membrane, individual molecular species of a phospholipid class are metabolized at different rates. Comparison of our results with previous studies of turnover of molecular classes of phospholipids indicates that in addition to polar head group composition (Miller et al., 1977), fatty acid composition is very important in determining the metabolic fate of a phospholipid. PMID- 1587823 TI - Characterization of a specific erythromegakaryocytic enhancer within the glycoprotein IIb promoter. AB - The gene coding for glycoprotein IIb (GPIIb), the alpha subunit of platelet integrin GPIIb/IIIa is an early and specific marker of the megakaryocytic lineage. Thus, studies on the regulation of this gene may provide helpful information on the mechanisms controlling cell specificity and differentiation in this lineage. The promoter region of this gene was isolated and analyzed to understand its tissue-specific transcriptional activity. A region extending from nucleotides -414 to -554 was found to be extremely important for the promoter function. Deletion of this region results in a 70% decrease of the promoter activity, as measured in CAT assays. This region has the properties of an enhancer. It is able to activate a heterologous promoter, in a distance- and orientation-independent manner, in both megakaryocytic and erythroid cells. This enhancer contains binding sites for nuclear factors and mutation of these sites, individually or together, abolish the enhancer activity. These nuclear factors are present in megakaryocytic and erythroid cell lineages, but they are absent in the other tested cells. One of the sites, named domain D, contains a TTATC motif that may interact with the transcription factor GATA1, active in erythroid and megakaryocytic cells. These results indicate that the promoter of a megakaryocytic gene contains a tissue specific enhancer, active in both the erythroid and the megakaryocytic lineages, and may implicate the erythroid factor GATA1. PMID- 1587824 TI - Reconstitution of the fatty acid hydroxylation function of cytochrome P-450BM-3 utilizing its individual recombinant hemo- and flavoprotein domains. AB - Cytochrome P-450BM-3 is a catalytically self-sufficient fatty acid omega hydroxylase with two domains. Functional and primary structure analyses of the hemo- and flavoprotein domains of cytochrome P-450BM-3 and the corresponding microsomal cytochrome P-450 system have shown that these proteins are highly homologous. Prior attempts to reconstitute the fatty acid hydroxylation function of cytochrome P-450BM-3, utilizing the two domains, obtained either by trypsinolysis or by recombinant methods, were unsuccessful. In this paper, we describe the reconstitution of the fatty acid hydroxylation activity of cytochrome P-450BM-3 utilizing the recombinantly produced flavoprotein domain (Oster, T., Boddupalli, S. S., and Peterson, J. A. (1991) J. Biol. Chem. 266, 22718-22725) and its hemoprotein counterpart. The rate of fatty acid-dependent oxygen consumption was shown to be linear when increasing concentrations of the hemoprotein domain are added to a fixed concentration of the flavoprotein domain and vice versa. The combination of the hemo- and flavoprotein domains in a ratio of 20:1 respectively, in the reaction mixture, results in the transfer of 80% of the reducing equivalents from NADPH for the hydroxylation of palmitate at 25 degrees C. The ratio of the regioisomeric products obtained for lauric, myristic, and palmitic acids was similar to that obtained with the holoenzyme form of cytochrome P-450BM-3. The reconstitution of the fatty acid omega-hydroxylase activity, using the soluble domains of cytochrome P-450BM-3, without added factors such as lipids, may be useful for structure/function comparisons to their eukaryotic counterparts. PMID- 1587825 TI - Development of an intracellular pool of glucose transporters in 3T3-L1 cells. AB - The membrane-impermeant bis-mannose photolabel 2-N-4-(1-azi-2,2,2 trifluoroethyl)benzoyl-1,3-bis-(D-mannos- 4-yloxy)-2- propylamine (ATB-BMPA) has been used to study the development of an intracellular pool of glucose transporters in 3T3-L1 cells. The subcellular distributions of the transporter isoforms GLUT1 and GLUT4 were determined by comparing the labeling obtained in cells in which the impermeant reagent only had access to the cell surface and the labeling obtained in digitonin-permeabilized cells. ATB-BMPA labeling showed that only GLUT1 was present in preconfluent fibroblasts and that most of the transporters were distributed to the cell surface. In preconfluent fibroblasts, the 2-deoxy-D-glucose transport activity was approximately 5 times higher than in confluent fibroblasts. ATB-BMPA labeling showed that the decrease in transport as cells reached confluence was associated with a decrease in the proportion of GLUT1 distributed to the cell surface. The sequestration of these transporters was associated with the development of an insulin-responsive transport activity which increased by approximately 2.5-fold compared with unstimulated confluent cells. ATB-BMPA labeling showed that insulin stimulation resulted in an approximately 2-fold increase in surface GLUT1 so that about one-half of the available transporters became recruited to the cell surface. Measurements of the changes in the distribution of both GLUT1 and GLUT4 throughout the differentiation of confluent fibroblasts into adipocytes showed that both transporters were sequestered in parallel. Basal levels of transport and photolabeling remained low throughout the differentiation period when the total pool of transporters (GLUT1 plus GLUT4) was increased by approximately 5-fold. These results suggest that the sequestration process was present before new transporters were synthesized. Thus, the sequestration mechanism develops in confluent growth-arrested fibroblasts although the capacity to sequester additional transporters may increase as differentiation proceeds. PMID- 1587826 TI - Kinetics and regulation of hepatoma mitochondrial NAD(P) malic enzyme. AB - Kinetic studies of Morris 7777 hepatoma mitochondrial NAD(P) malic enzyme were consistent with an ordered mechanism where NAD adds to the enzyme before malate and dissociation of NADH from the enzyme is rate-limiting. In addition to its active site, malate apparently also associates with a lower affinity with an activator site. The activator fumarate competes with malate at the activator site and facilitates dissociation of NADH from the enzyme. The ratio of NAD(P) malic enzyme to malate dehydrogenase activity in the hepatoma mitochondrial extract was found to be too low, even in the presence of known inhibitors of malate dehydrogenase, to account for the known ability of NAD(P) malic enzyme to intercept exogenous malate from malate dehydrogenase in intact tumor mitochondria (Moreadith, R.W., and Lehninger, A.L. (1984) J. Biol. Chem. 259, 6215-6221). However, NAD(P) malic enzyme may be able to intercept exogenous malate because according to the present results, it can associate with the pyruvate dehydrogenase complex, which could localize NAD(P) malic enzyme in the vicinity of the inner mitochondrial membrane. The activity levels of some key metabolic enzymes were found to be different in Morris 7777 mitochondria than in liver or mitochondria of other rapidly dividing tumors. These results are discussed in terms of differences among tumors in their ability to utilize malate, glutamate, and citrate as respiratory fuels. PMID- 1587827 TI - Requirement for three membrane-spanning alpha-helices in the post-translational insertion of a thylakoid membrane protein. AB - The insertion of a protein into a lipid bilayer usually involves a short signal sequence and can occur either during or after translation. A light-harvesting chlorophyll a/b-binding protein (LHCP) is synthesized in the cytoplasm of plant cells as a precursor and is post-translationally imported into chloroplasts where it subsequently inserts into the thylakoid membrane. Only mature LHCP is required for insertion into the thylakoid. To define which sequences of the mature protein are necessary and sufficient for thylakoid integration, fusion and deletion proteins and proteins with internal rearrangements were synthesized and incubated with isolated thylakoids and stroma. No evidence is found for the existence of a short signal sequence within LHCP, and, with the exception of the amino terminus and a short lumenal loop, the entire mature protein with consecutively ordered alpha-helices is required for insertion into thylakoid membranes. The addition of positive charges into stromal but not lumenal segments permits the insertion of mutant LHCPs into isolated thylakoids. Replacement of the LHCP transit peptide with the transit peptide from plastocyanin has no effect on LHCP insertion and does not restore insertion of the lumenal charge addition mutants. PMID- 1587828 TI - Maturation of isoprenylated proteins in Saccharomyces cerevisiae. Multiple activities catalyze the cleavage of the three carboxyl-terminal amino acids from farnesylated substrates in vitro. AB - Eukaryotic polypeptides containing COOH-terminal-CXXX sequences can be posttranslationally modified by isoprenylation of the cysteine residue via a thioether linkage, proteolytic removal of the three terminal amino acids, and alpha-carboxyl methylation of the cysteine residue. Through the development of an indirect coupled assay, we have identified three in vitro activities in the yeast Saccharomyces cerevisiae that can catalyze the proteolytic cleavage of the three COOH-terminal amino acids of the synthetic peptide substrate N-acetyl-KSKTK[S farnesyl-Cys]VIM. One of these is the vacuolar protease carboxypeptidase Y. Using a mutant strain deficient in this enzyme, we find evidence for an additional soluble activity as well as for a membrane-associated activity. These latter activities are candidates for roles in the physiological processing of isoprenylated protein precursors. They are both insensitive to inhibitors of serine and aspartyl proteinases but are sensitive to sulfhydryl reagents and 0.5 mM ZnCl2. The soluble activity appears to be a metalloenzyme, inhibitable by 2 mM o-phenanthroline but not by 1 mM N-ethylmaleimide, whereas the membrane associated enzyme is inhibitable by 1 mM N-ethylmaleimide but not 2 mM o phenanthroline. We show that the membrane-bound protease is not an activity of the membrane-bound methyltransferase, because protease activity is observed in membrane preparations that lack the STE14-encoded methyltransferase. The soluble activity appears to be a novel carboxypeptidase of approximately 110 kDa that catalyzes a processive removal of amino acids from the COOH terminus from both the farnesylated and non-farnesylated substrate, but not from three other unrelated peptides. Finally, we find no evidence for non-vacuolar membrane or soluble activities that catalyze the ester hydrolysis of N-acetyl-S-farnesyl-L cysteine methyl ester. PMID- 1587829 TI - DNA binding activities of c-Myc purified from eukaryotic cells. AB - c-Myc is a nuclear phosphoprotein which contains both a leucine zipper and a helix-loop-helix dimerization motif. These are adjacent to a basic region believed to make specific contacts with DNA upon dimerization. We report the purification of full-length c-Myc to near homogeneity from two independent eukaryotic systems: the baculovirus overexpression system using an insect cell host, and Chinese hamster ovary cells containing heat-inducible c-myc genes. The DNA binding capabilities of these preparations were characterized. Both preparations contain two distinct activities that bind specifically to sequences with a core of CACGTG. The Myc protein is solely responsible for one of these binding activities. Specific sequences that bound to c-Myc were selected from a large pool of random DNA sequence. Sequencing of individual binding sites selected by this procedure yielded a 12-base consensus, PuACCACGTGCTC, for c-Myc binding. Both protein preparations additionally demonstrated a distinct complex, containing both c-Myc and a copurifying 26-29-kDa protein, that bound to DNA with higher affinity than Myc alone. Selection of specific DNA sequences by this complex revealed a consensus binding site similar to the 12-base consensus described above. These data demonstrate that c-Myc isolated from eukaryotic cells is capable of sequence-specific DNA binding and further refine the optimal sequence for c-Myc binding. These protein preparations should prove useful in further characterizing the biochemical properties of c-Myc. PMID- 1587830 TI - Structure of the noncompetitive antagonist-binding site of the Torpedo nicotinic acetylcholine receptor. [3H]meproadifen mustard reacts selectively with alpha subunit Glu-262. AB - [3H]Meproadifen mustard, an affinity label for the noncompetitive antagonist site of the nicotinic acetylcholine receptor (AChR), specifically alkylates the AChR alpha-subunit when the acetylcholine-binding sites are occupied by agonist (Dreyer, E. B., Hasan, F., Cohen, S. G., and Cohen, J. B. (1986) J. Biol. Chem. 261, 13727-13734). In this report, we identify the site of alkylation within the alpha-subunit as Glu-262. AChR-rich membranes from Torpedo californica electric organ were reacted with [3H]meproadifen mustard in the presence of carbamylcholine and in the absence or presence of nonradioactive meproadifen to define specific alkylation of the noncompetitive antagonist site. Alkylated alpha subunits were isolated and subjected to chemical or enzymatic cleavage. When digests with CNBr in 70% trifluoroacetic acid or 70% formic acid were fractionated by gel filtration high performance liquid chromatography (HPLC), specifically labeled material was recovered in the void volume fractions. Based upon NH2-terminal sequence analysis, for both digests, the void volume fractions contained a fragment beginning at Gln-208 before the M1 hydrophobic sequence, whereas the sample from the digest in trifluoroacetic acid also contained as a primary sequence a fragment beginning at Thr-244 and extending through the M2 hydrophobic sequence. Sequence analysis revealed no release of 3H for the sample from digestion in formic acid, whereas for the trifluoroacetic acid digest, there was specific release of 3H in cycle 19, which would correspond to Glu-262. This site of alkylation was confirmed by isolation by sodium dodecyl sulfate polyacrylamide gel electrophoresis and reversed-phase HPLC of a specifically labeled fragment from an endoproteinase Lys-C digest of the alkylated alpha subunit. NH2-terminal amino acid sequencing revealed release of 3H at cycle 20 from a fragment beginning at Met-243 and extending into the M3 hydrophobic sequence. Because [3H]meproadifen mustard contains, as its reactive group, a positively charged quaternary aziridinium ion, Glu-262 of the alpha-subunit is identified as a contributor to the cation-binding domain of the noncompetitive antagonist-binding site and thus of the ion channel. PMID- 1587831 TI - 2-Keto-4-hydroxyglutarate aldolase: purification and characterization of the homogeneous enzyme from bovine kidney. AB - 2-Keto-4-hydroxyglutarate aldolase, which catalyzes the reversible cleavage of 2 keto-4-hydroxyglutarate, yielding pyruvate plus glyoxylate, has been purified from extracts of bovine kidney to apparent homogeneity as judged by polyacrylamide gel electrophoresis, gel filtration chromatography, sucrose density gradient centrifugation, and meniscus depletion sedimentation equilibrium experiments. The enzyme from this source has a native and a subunit mass of 144 and 36 kDa, respectively; the pH-activity optimum is 8.8. Rather than being stimulated, aldolase activity is inhibited to varying degrees by added divalent metal ions, whereas a number of metal ion-chelating agents have no effect. An absolute requirement for added thiol compounds could not be shown, but 2 mercaptoethanol enhances activity 2-fold, and added Hg2+ as well as p mercuribenzoate or dithiodipyridine markedly inhibit catalysis. Incubation of the enzyme with either pyruvate or glyoxylate in the presence of NaBH4 causes extensive loss of aldolase activity concomitant with stable binding of approximately 1.0-1.5 mol of 14C-labeled substrate/mol of enzyme. The circular dichroism spectrum for native aldolase is characteristic of an alpha-helix; incubation of the enzyme with glyoxylate has no effect on this spectrum, but it is considerably altered by pyruvate. Bovine kidney aldolase shows no stereospecificity in catalyzing the aldol cleavage of the two optical isomers of 2-keto-4-hydroxyglutarate, and although it also catalyzes the beta decarboxylation of oxalacetate, its decarboxylase/aldolase activity ratio is lower than that seen with the pure enzyme from either bovine liver or Escherichia coli. PMID- 1587832 TI - Identification, purification, and characterization of a protein activator (PA28) of the 20 S proteasome (macropain). AB - A protein that greatly stimulates the multiple peptidase activities of the 20 S proteasome (also known as macropain, the multicatalytic protease complex, and 20 S protease) has been purified from bovine red blood cells and from bovine heart. The activator protein was a single polypeptide with an apparent molecular weight of 28,000, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and had a native molecular weight of approximately 180,000. This protein, which we have termed PA28, regulated all three of the putatively distinct peptidase activities displayed by each of two functionally different forms of the proteasome. This regulation usually included both an increase in the maximal reaction velocity and a decrease in the concentration of substrate required for half-maximal velocity and indicated that PA28 acted as a positive allosteric effector of the proteasome. PA28 failed, however, to stimulate the hydrolysis of large protein substrates such as casein and lysozyme. These results suggested that the hydrolysis of protein substrates occurred at a site or sites distinct from those that hydrolyzed small peptides and that the regulation of the two processes could be uncoupled. Evidence for direct binding of PA28 to the proteasome was obtained by glycerol density gradient centrifugation. PA28 may play an important regulatory role in intracellular proteolytic pathways mediated by the proteasome. PMID- 1587833 TI - Measurement of the substrate dissociation constant of a solubilized membrane carrier. Substrate stabilization of OxlT, the anion exchange protein of Oxalobacter formigenes. AB - OxlT, a secondary carrier found in Oxalobacter formigenes, mediates the exchange of divalent oxalate and monovalent formate. Because OxlT has an unusually high turnover number (greater than or equal to 1000/s), and because formate, one its substrates, shows high passive membrane permeability as formic acid, it has been difficult to obtain information on protein-substrate interactions using traditional methods in membrane biology. For this reason, we devised a new way to measure substrate dissociation constants. Detergent-solubilized material was exposed to inactivating temperatures in the absence or presence of OxlT substrates, and periodic reconstitution was used to monitor the kinetics of thermal decay. The data were consistent with a simple scheme in which only unliganded OxlT was temperature-sensitive; this premise, along with the assumption of equilibrium between liganded and unliganded species, allowed calculation of substrate dissociation constants for oxalate (18 +/- 3 microM), malonate (1.2 +/- 0.2 mM), and formate (3.1 +/- 0.6 mM). Further analysis revealed that substrate binding energy contributed at least 3.5 kcal/mol to stabilization of solubilized OxlT. Accordingly, we suggest that substrate binding energy is directly involved in driving protein structure reorganization during membrane transport. This new approach to analyzing protein-substrate interactions may have wider application in the study of membrane carriers. PMID- 1587834 TI - Identification, purification, and reconstitution of OxlT, the oxalate: formate antiport protein of Oxalobacter formigenes. AB - We had proposed earlier that the anaerobe Oxalobacter formigenes sustains a proton-motive force by exploiting a secondary carrier rather than a primary proton pump. In this view, a carrier protein would catalyze the exchange of extracellular oxalate, a divalent anion, and intracellular formate, the monovalent product of oxalate decarboxylation. Such an electrogenic exchange develops an internally negative membrane potential, and since the decarboxylation reaction consumes an internal proton, the combined activity of the carrier and the soluble decarboxylase would constitute an "indirect" proton pump with a stoichiometry of 1H+ per turnover. This model is now verified by identification and purification of OxlT, the protein responsible for the anion exchange reaction. Membranes of O. formigenes were solubilized at pH 7 with 1.25% octyl glucoside in 20 mM 3-(N-morpholino)propanesulfonic acid/K, in the presence of 0.4% Escherichia coli phospholipids and with 20% glucerol present as the osmolyte stabilant. Rapid methods for reconstitution were developed to monitor the distribution of OxlT during biochemical fractionation, allowing its purification by sequential anion and cation exchange chromatography. OxlT proved to be a single hydrophobic polypeptide, of 38 kDa mobility during sodium dodecyl sulfate polyacrylamide gel electrophoresis, with a turnover number estimated as at least 1000/s. The properties of OxlT point to an indirect proton pump as the mechanism by which a proton-motive force arises in O. formigenes, and one may reasonably argue that indirect proton pumps take part in bacterial events such as acetogenesis, malolactate fermentation, and perhaps methanogenesis. PMID- 1587835 TI - Posttranscriptional control of glutathione S-transferase pi gene expression in human breast cancer cells. AB - The glutathione S-transferase pi gene (GST pi) is highly expressed in estrogen receptor negative (ER-) but not expressed in ER+ human breast cancer cell lines. To define regulatory mechanisms of GST pi gene expression, we analyzed both the activity of the GST pi promoter and the posttranscriptional fate of GST pi RNA sequences in three ER+ and three ER- breast cancer cell lines. Expression of a transiently transfected CAT reporter gene driven by the GST pi promoter and 2203 nucleotides of 5'-flanking sequences were similar in all six cell lines regardless of ER status. Endogenous GST pi transcription rates in nuclei isolated from ER- cells were quite low despite high steady state levels of cytoplasmic mRNA. Furthermore, the endogenous GST pi gene was transcribed in ER+ nuclei at rates similar to those obtained in ER- nuclei. We determined the stabilities of mRNAs transcribed from the endogenous GST pi gene (ER- cells) and from a stably transfected GST pi cDNA expression vector (ER+ and ER- cells). The endogenous GST pi mRNA was extraordinarily stable in ER- cells. Comparisons between transfected ER+ and ER- cells revealed no significant differences in the stabilities of transfection-derived GST pi mRNA sequences. We conclude that GST pi mRNA stability contributes significantly to the high levels of cytoplasmic mRNA observed in ER- cells, but that the differential expression of GST pi in ER+ versus ER- cells is governed by other posttranscriptional processes. PMID- 1587836 TI - The purification, characterization, and primary structure of a small redox protein from Methanobacterium thermoautotrophicum, an archaebacterium. AB - A small redox-active protein has been purified to homogeneity from cell-free extracts of the strictly anaerobic thermophilic methanogen, Methanobacterium thermoautotrophicum (strain Marburg). The purification consisted of streptomycin sulfate and acid treatments and three chromatographic steps using Sephadex G-75, Mono Q HR 10/10, and Superose 12 HR 10/30 columns. When these procedures were carried out under strictly anaerobic conditions, approximately 3 mg of this protein could be isolated from 45 g of wet cell paste. Like the thioredoxins and glutaredoxins, it is a small acidic protein (pI = 4.2) consisting of 83 amino acids (M(r) = 9136). In the presence of dithiothreitol or dihydrolipoate, the protein serves as a hydrogen donor for the ribonucleotide reductase from Escherichia coli, and it catalyzes the reduction of insulin. However, it does not interact with the thioredoxin reductases from E. coli or Corynebacterium nephridii and does not function as a hydrogen donor for the ribonucleotide reductase of C. nephridii. The amino acid sequences determined by automated Edman degradation of the 14C-carboxymethylated protein and of peptides derived from trypsin and chymotrypsin digestions show a redox-active site -Cys-Pro-Tyr-Cys-, typical of the glutaredoxins. Its amino acid sequence shows moderate identity with the known glutaredoxins (E. coli, yeast, rabbit bone marrow, calf thymus, and pig liver) when the proteins are aligned at the active site. The secondary structure of the glutaredoxin-like protein predicted by the Chou-Fasman procedure shows that it is similar to the known glutaredoxins. However, surprisingly, the protein does not function as a glutathione-disulfide oxidoreductase in the presence of glutathione and glutathione reductase. This glutaredoxin-like protein may be a component of a ribonucleotide-reducing system distinct from the previously described systems utilizing thioredoxin or glutaredoxin. PMID- 1587837 TI - Purification and characterization of the vacuolating toxin from Helicobacter pylori. AB - A vacuolating toxin was purified to homogeneity from broth culture supernatant of the human gastric bacterium, Helicobacter pylori. The procedure for isolating the toxin included ammonium sulfate precipitation, hydrophobic interactive chromatography, size exclusion chromatography, and anion exchange chromatography, which together resulted in a greater than 5000-fold purification of toxin activity. The molecular mass of the purified, denatured toxin was 87,000 +/- 320 daltons, and the native toxin was an aggregate with a molecular mass greater than or equal to 972,000 daltons. The amino-terminal sequence of the purified toxin was partially homologous with internal sequences of numerous transport or ion channel proteins. Antiserum raised against the M(r) = 87,000 protein neutralized toxin activity, whereas preimmune serum did not. When reacted with specific antiserum to the M(r) = 87,000 protein in an enzyme-linked immunosorbent (ELISA) assay, culture supernatants from eight tox+ H. pylori strains produced significantly higher optical density readings than eight tox- supernatants (0.614 +/- 0.11 versus 0.046 +/- 0.01, p less than 0.0001). Sera from H. pylori-infected humans recognized the purified M(r) = 87,000 protein significantly better by ELISA than sera from uninfected persons (0.424 +/- 0.06 versus 0.182 +/- 0.02, p = 0.0009). Finally, ELISA recognition of the purified M(r) = 87,000 protein by human sera was significantly associated with toxin-neutralizing activity (p = 0.019, r = 0.518). PMID- 1587838 TI - Replacement of a conserved arginine in the assembly domain of ribulose-1,5 bisphosphate carboxylase/oxygenase small subunit interferes with holoenzyme formation. AB - In higher plants the small subunit (S) of ribulose-1,5-bisphosphate carboxylase/oxygenase (ribulose-P2 carboxylase, EC 4.1.1.39) contains a segment of 16 amino acids which is absent from cyanobacterial S. This segment connecting two beta sheets has been shown, by crystallographic analysis, to form a hairpin loop. The quaternary structure of ribulose-P2 carboxylase indicates several S to large subunit (L) interactions. Eleven of 22 residues within the loop form the interface with 20 residues from two different L dimers. Eight of the loop residues are involved in hydrogen bonds, salt links, and hydrophobic interactions. To test the hypothesis, whether this loop had a function in the assembly of L and S into the hexadecameric enzyme, 6 amino acids within the loop were modified by site-directed mutagenesis of the pea rbcS-3A gene. All substituted S were imported by isolated chloroplasts from pea with wild type efficiency. Mutants E54-R, H55-A, P59-A, D63-G, D63-L, and Y66-A were assembly competent, indicating that changes of side chains at these positions are tolerated. Replacement of arginine 53, whose side chain forms H-bonds with L residues Y226 and G261, with glutamate completely abolished assembly into holoenzyme. We suggest that arginine 53 in S is essential for ribulose-P2 carboxylase quaternary structure in higher plants. PMID- 1587839 TI - Human growth hormone enhances pertussis toxin-stimulated ADP-ribosylation of Gi in Nb2 cell membrane. AB - The Nb2 node lymphoma cell line has been widely used as a model for investigating lactogen cellular actions. Both pertussis (PTX) and cholera (CTX) toxins modulate lactogen-stimulated Nb2 cell mitogenesis, suggesting G protein involvement in lactogen signal transduction. The following studies were performed to further investigate this possibility. Both PTX-sensitive (41 kDa) and CTX-sensitive substrates (42 and 45 kDa) were identified in Nb2 cell membrane and recognized by specific anti-Gi and anti-Gs antibodies, respectively. Equal numbers of Nb2 cells were then incubated with the lactogen human growth hormone (hGH, 10 ng/ml) for 0 72 h. Membrane protein prepared from each time point (50 micrograms) was compared in toxin-stimulated ADP-ribosylation studies. CTX-stimulated ADP-ribosylation was unaffected by prior hGH incubation. PTX-stimulated ADP-ribosylation increased 237 +/- 69% (X +/- S.E.) compared with 0-h controls (n = 11; p less than 0.01) after 4-7 h of hGH incubation then decreased toward 0-h samples by 24 and 72 h. No change in Gi alpha concentration was observed, but beta subunit concentration increased (145 +/- 14% at 7 h; p less than 0.01; n = 3) in a time course that paralleled the changes in PTX-stimulated ADP-ribosylation. In summary, 1) both Gi and Gs were present in Nb2 cell membrane, 2) incubation of cells with a lactogen, hGH, for 4-7 h markedly enhanced PTX-stimulated ADP-ribosylation of Gi alpha in vitro, whereas CTX-stimulated ADP-ribosylation of Gs alpha was unchanged, and 3) although no change in Gi alpha concentration was observed, beta subunit concentration increased in parallel with the increase in PTX-stimulated ADP ribosylation of Gi alpha. These results suggest that hGH may modify PTX stimulated ADP-ribosylation of Gi not by changing Gi alpha concentration, perhaps by increasing beta subunit concentration, enhancing association of Gi alpha by beta gamma subunits, which, in turn, is preferentially ADP-ribosylated. This may represent a late signal transduction event and may also have implications for other effectors dependent on Gi-mediated events. PMID- 1587840 TI - Hemopexin is synthesized in peripheral nerves but not in central nervous system and accumulates after axotomy. AB - In adult mammals, injured axons regrow over long distances in peripheral nerves but fail to do so in the central nervous system. Analysis of molecular components of tissue environments that allow axonal regrowth revealed a dramatic increase in the level of hemopexin, a heme-transporting protein, in long-term axotomized peripheral nerve. In contrast, hemopexin did not accumulate in lesioned optic nerve. Sciatic nerve and skeletal muscle, but not brain, were shown to be sites of synthesis of hemopexin. Thus, hemopexin expression, which can no longer be considered to be liver-specific, correlates with tissular permissivity for axonal regeneration. PMID- 1587841 TI - Developmental patterns of ganglioside sialosylation coincident with neuritogenesis in cultured embryonic chick brain neurons. AB - Chick brain precursor neurons were observed to introduce sialic acid biosynthetically into only three specific gangliosides: monosialosyl lactosyl ceramide (GM3), disialosyl lactosyl ceramide (GD3), and disialosyl gangliotrihexosyl ceramide (GD2), when sialic acid was labeled metabolically by its obligate precursor, [3H] ManNAc. Sialosyl donor CMP-[3H]NeuAc supplied in the culture medium gave rise uniquely to surface-labeled GD3. Thus sialosyl transferase/GD3 synthase activity is expressed both intraneuronally and in the neuronal exofacial surface. Upon epidermal growth factor-induced onset of neurite outgrowth, labeled complex sialosyl gangliotetrahexosyl ceramide species of gangliosides began to appear in the embryonic neuronal plasma membrane. However, intraneuronal and exofacial sialosyl transferase/GD3 synthase activities remained constant, with or without neurite outgrowth. Moreover, simpler species of gangliosides maintained a steady quantitative sialosyl level (1.6 +/- 0.2 micrograms of sialic acid/mg of protein), whereas more complex species completely absent before neurite outgrowth accrued and reached 4.8 +/- 0.9 micrograms of sialic acid/mg of protein with full neurite development. This analysis of developmental patterns of ganglioside sialosylation has provided evidence that stable neurite outgrowth depends upon generation by the neuron of special plasma membrane with a massive content of complex higher species of gangliosides. PMID- 1587842 TI - Cloning and sequence analysis of cDNA for a neuronal cell membrane antigen, HPC 1. AB - A monoclonal antibody (mAb), HPC-1, labels the plasma membrane of the amacrine cell soma and inner plexiform layer in rat retina and other central neurons. HPC 1 antigen recognizes several proteins of about 35 kDa. In this study, an HPC-1 positive cDNA, HPC-113, was isolated from a lambda gt11 cDNA library of the rat hippocampus. HPC-113 had the 894-base pair nucleotide sequence in an open reading frame and the calculated molecular mass of the deduced amino acid sequence (298 residues) was 33,989 Da, implying that HPC-113 contains almost the full-length coding region of HPC-1 antigen is an integrated membrane protein revealing the characteristic alpha-helical structure with periodical heptad repeats usually seen in proteins with coiled-coil structures. Although the entire amino acid sequence did not show significant homology to any proteins so far known, a few local sequences in the possible extracellular domain of the HPC-1 antigen molecule had notable homology to some partial sequences in the laminin B1 chain. These sequences of laminin are included in the portion which has neurite outgrowth and/or survival promoting activity. The HPC-1 gene was transcribed in nerve tissues much more predominantly than in non-neuronal tissues. Thus, HPC-1 antigen(s) was confined to be a newly identified neuronal cell membrane protein(s) localized in a subpopulation of neurons. PMID- 1587843 TI - Ras transformation of cloned rat embryo fibroblasts results in increased rates of protein synthesis and phosphorylation of eukaryotic initiation factor 4E. AB - Eukaryotic initiation factor 4E (eIF-4E) is a 25-kDa phosphoprotein that binds to the 7-methylguanosine cap of mRNA and acts, along with other eIF-4 polypeptides, to unwind mRNA secondary structure at the 5' terminus. Recent studies have indicated that eIF-4E acts as a protooncogene, but only in its phosphorylated state. In order to determine the role of eIF-4E in oncogenesis, we examined its regulation and expression in cloned rat embryo fibroblasts transformed with the Harvey ras (Ha-ras) oncogene. The expression of Ha-ras increased the rate of protein synthesis but did not increase the levels of eIF-4E mRNA or protein. However, a dramatic increase (7-fold) in phosphate incorporation into eIF-4E was observed. The percentage of eIF-4E in the phosphorylated state was the same in transfected and control cells, indicating that both phosphorylation and dephosphorylation of eIF-4E were increased. Phosphopeptide mapping of eIF-4E from transformed cells indicated a single site of phosphorylation at Ser-53, which is the same as that identified previously in eIF-4E from reticulocytes and HeLa cells. These results indicate that p21ras is part of the signal transduction pathway leading to phosphorylation of eIF-4E. These findings also provide a potential mechanism for cell transformation by p21ras which involves the preferential stimulation of translation of certain mRNAs. PMID- 1587844 TI - Serum T-kininogen levels increase two to four months before death. AB - We have reported an accumulation of T-kininogen mRNA in the liver of aging Sprague-Dawley rats. T-kininogen is a cysteine proteinase inhibitor. Since a disruption of the intracellular protein degradation machinery is known to occur during senescence, we wished to further define the role of this protein in the aging process. As a first step, we have measured T-kininogen levels both in serum and within the liver. We have found that serum protein levels are indeed augmented during senescence, although not as dramatically as the mRNA (2.5-fold versus 8.3-fold). Immunocytochemistry, as well as Western blot analysis suggests that this is due to the presence of T-kininogen within hepatic cells in aged rats. Life-long dietary restriction, a known age-prolonging treatment, decreases the overexpression of the protein in 24-month-old rats. Later, diet-restricted animals still show an increased expression from the gene, the effect being delayed but not abolished by dietary manipulation. Interestingly, a longitudinal study indicated the existence of a positive correlation between the time of increase of serum T-kininogen and the time of death of the animal. Serum T kininogen was found to increase 2.5-4 months before death. PMID- 1587845 TI - N-linked glycosylation of rabies virus glycoprotein. Individual sequons differ in their glycosylation efficiencies and influence on cell surface expression. AB - Many eukaryotic proteins are modified by N-linked glycosylation, a process in which oligosaccharides are added to asparagine residues in the sequon Asn-X Ser/Thr. However, not all such sequons are glycosylated. For example, rabies virus glycoprotein (RGP) contains three sequons, only two of which appear to be glycosylated in virions. To examine further the signals in proteins which regulate N-linked core glycosylation, the glycosylation efficiencies of each of the three sequons in the antigenic domain of RGP were compared. For these studies, mutants were generated in which one or more sequons were deleted by site directed mutagenesis. Core glycosylation of these mutants was studied using two independent systems: 1) in vitro translation in rabbit reticulocyte lysate supplemented with dog pancreatic microsomes, and 2) transfection into glycosylation-deficient Chinese hamster ovary cells. Parallel results were obtained with both systems, demonstrating that the sequon at Asn37 is inefficiently glycosylated, the sequons at Asn247 and Asn319 are efficiently glycosylated, and the glycosylation efficiency of each sequon is not influenced by glycosylation at other sequons in this protein. High levels of cell surface expression of RGP in Chinese hamster ovary cells are seen with any mutant containing an intact sequon at Asn247 or Asn319, whereas low levels of cell surface expression are seen when the sequon at Asn37 is present alone; deletion of all three sequons completely blocks RGP cell surface expression. Thus, although core glycosylation at Asn37 is inefficient, it is still sufficient to support a biological function, cell surface expression. Future studies using mutagenesis of this model protein and its expression in these two well defined systems will aim to begin to unravel the rules governing core glycosylation of glycoproteins. PMID- 1587846 TI - Changes in the relative amount of subunits of methionine adenosyltransferase in human lymphocytes upon stimulation with a polyclonal T cell mitogen. AB - Activation of resting human peripheral blood T lymphocytes by the lectin phytohemagglutinin results in an increase in methionine adenosyltransferase (MAT) activity, accompanied by an increase in the amount of the alpha/alpha' catalytic subunits of the enzyme. In contrast, the amount of the noncatalytic beta subunit remains constant throughout the course of the response. Using both polyclonal antibodies to the holoenzyme and monoclonal antibodies to the alpha/alpha' subunits, we detected a cross-reactive 68-kDa protein, which we refer to as lambda. This protein is present in high abundance in resting T cells but decreases upon cell stimulation, as both MAT activity and the amount of the catalytic alpha/alpha' subunits increase. The decrease in lambda and increase in alpha/alpha' occurs after interleukin-2 production and before DNA synthesis. lambda virtually disappears when the cells are actively dividing. Several continuous T cell lines (HPB-ALL, MOLT-4, and Jurkat) as well as a freshly isolated T cell leukemia (ALL-2) had no detectable lambda. The Km for L methionine for enzyme from resting peripheral blood mononuclear cells was 19-23 microM, which is 3-8-fold higher than purified MAT from fresh leukemic cells or enzyme from Jurkat cells, both of which have a Km of 3.5-3.8 microM. Kinetic analysis of enzyme activity from activated peripheral blood mononuclear cells suggested the presence of two forms of enzyme catalyzing the synthesis of AdoMet. After separation of lambda from the alpha and beta subunits by hydrophobic chromatography, it was determined that lambda has MAT activity but that it is significantly less active than the form containing the alpha subunit. It therefore appears that in resting T cells MAT is sequestered as a less active form. We hypothesize that lambda is a precursor to the catalytic subunits of human lymphocyte MAT and propose that the transition from lambda to alpha/alpha' may be important in the response of T cells to mitogenic signals. PMID- 1587847 TI - Glucagon gene 5'-flanking sequences direct expression of simian virus 40 large T antigen to the intestine, producing carcinoma of the large bowel in transgenic mice. AB - Glucagon and the glucagon-like peptides play important roles in the regulation of glucose homeostasis. Previous studies have demonstrated that approximately 1300 base pairs of rat glucagon gene 5'-flanking sequences direct transgene expression to the pancreas and brain, but not to the intestine, of transgenic mice. These observations suggested that different tissue-specific enhancer elements mediate activation of glucagon gene transcription in the pancreas and intestine. We have now generated mice that express SV40 large T antigen under the control of approximately 2000 base pairs of glucagon gene 5'-flanking sequences. Transgene expression was observed in the brain and pancreas in association with the development of pancreatic endocrine tumors. In contrast to the mice described previously, we also detected transgene expression throughout the gastrointestinal tract in endocrine cells of the stomach and small and large intestine. Focal areas of enteroendocrine cell hyperplasia in the large bowel invariably progressed to invasive and metastasizing plurihormonal endocrine carcinoma, which was clinically and pathologically evident by 4 weeks of age. In contrast, transgene expression in the small bowel and stomach was not associated with progression to either hyperplasia or carcinoma. The results of these studies provide functional evidence for the existence of an upstream cis-acting regulatory domain that directs glucagon gene transcription to the endocrine cells of the intestine in transgenic mice. PMID- 1587848 TI - Microtubules and microtubule-associated proteins in resting and mitogenically activated normal human peripheral blood T cells. AB - The binding of an appropriate ligand to its specific receptor on the membrane of T cells triggers a cascade of events involved in T cell activation. An important yet unanswered question is how the mitogenic signals are transmitted through the cytoplasm and into the nucleus. The present study was carried out to determine changes in the microtubule (MT) system, following T cell activation. Fluorescence microscopy was employed to examine the organization of the microtubule network in human peripheral blood T cells in response to four different mitogens (phytohemagglutinin, concanavalin A, anti-CD3, and phorbol 12-myristate 13 acetate). The microtubules increase in length, number, and complexity of distribution 20 h after mitogenic stimulation. Using an in situ direct analysis protocol consisting of selective extraction of cells with detergent and Ca2+, 11 protein species, which fulfill the operational definition of microtubule associated proteins (MAPs), were identified in resting human T cells. Alterations in the expression of these protein species were studied following mitogenic stimulation. These alterations in MAPs expression were also found in purified blast cell fractions indicating that they were specific changes occurring in activated T cell populations. These observations suggest a role for MT and MAPs in the cascade of human T cell activation. PMID- 1587849 TI - Lipolysis is a prerequisite for lipid accumulation in HepG2 cells induced by large hypertriglyceridemic very low density lipoproteins. AB - Lipoprotein kinetic studies have demonstrated that a large proportion of Sf 60 400 very low density lipoprotein (VLDL) is cleared directly from the circulation in Type IV hypertriglyceridemic subjects, at an unknown tissue site. The present studies were designed to investigate the role of hepatocytes in this process and to define the conditions, whereby Type IV Sf 60-400 VLDL would induce lipid accumulation in HepG2 cells. Type IV VLDL (Sf 60-400) failed to augment the total cholesterol, esterified cholesterol, or triglyceride content of HepG2 cells following 24-h incubations. Coincubation of bovine milk lipoprotein lipase (LPL) and Type IV VLDL with HepG2 cells induced a 3-fold increment in cellular esterified cholesterol mass (p less than 0.005) and a 7-fold increase in cellular triglyceride mass (p less than 0.005), compared to VLDL alone. The increased cellular lipid mass was associated with increased oleate incorporation into cellular cholesterol esters and triglycerides. Exogenous LPL hydrolyzed 76% of the VLDL triglyceride over 24 h. LPL action on Type IV VLDL was sufficient to promote cellular uptake of these lipoproteins, while elevated media-free fatty acid levels were not. Although HepG2 cells secrete apolipoprotein (apo) E, we assessed the role of VLDL-associated apoE in the lipid accumulation induced by VLDL plus LPL. ApoE-rich and apoE-poor Type IV VLDL subfractions induced similar increments in cellular esterified cholesterol in the presence of LPL, despite a 4 fold difference in apoE content. Sf 60-400 VLDL, from subjects homozygous for the defective apoE2, plus LPL, behaved identically to Type IV VLDL plus LPL. Type IV VLDL plus LPL, preincubated with anti-apoE (1D7) and apoB (5E11) monoclonal antibodies, known to block the binding of apoE and -B, respectively, to the LDL receptor failed to block lipid accumulation. In contrast, apoE-poor Type IV VLDL, apoE2 VLDL, and VLDL plus 1D7 were taken up poorly by J774 cells, cells that secrete LPL, but not apoE. These studies suggest that lipolytic remodeling of large Type IV VLDL by LPL is a prerequisite for their uptake by HepG2 cells and that HepG2 cell-secreted apoE rather than VLDL-associated apoE is the ligand involved in uptake. PMID- 1587850 TI - Functional expression of a full-length cDNA coding for rat neural cell adhesion molecule L1 mediates homophilic intercellular adhesion and migration of cerebellar neurons. AB - Neural cell adhesion molecule L1 is postulated to be involved in cell-cell interaction, neurite elongation, fasciculation of axons, cell migration, and myelination. To determine the function of L1 directly, we have transfected rat L1 cDNA into mouse fibroblast L cells. Stable transformants expressing L1 showed uniform surface expression of the molecule without phenotypic changes. Dispersed L1-expressing transfectants aggregated with faster kinetics than control cells in a homophilic manner. Divalent cations were not required for this cell aggregation. L1-transfected cells markedly enhanced neuronal cell adhesion and migration in co-culture with rat cerebellar neurons. These results indicate that L1 is involved in a determinant step of neural development through molecular interactions. PMID- 1587851 TI - Cloning, expression, and characterization of the unique bovine A1 adenosine receptor. Studies on the ligand binding site by site-directed mutagenesis. AB - The bovine brain A1 adenosine receptor (A1AR) is distinct from other A1ARs in that it displays the unique agonist potency series of N6-R phenylisopropyladenosine (R-PIA) greater than N6-S-phenylisopropyladenosine (S PIA) greater than 5'-N-ethylcarboxamidoadenosine and has a 5-10-fold higher affinity for both agonists and antagonists. The cDNA for this receptor has been cloned from a size-selected (2-4-kb) bovine brain library and sequenced. The 2.0 kb cDNA encodes a protein of 326 amino acid residues with a molecular mass of 36,570 daltons. The amino acid sequence fits well into the seven-transmembrane domain motif typical of G protein-coupled receptors. Northern analysis in bovine tissue using the full length cDNA demonstrates mRNAs of 3.4 and 5.7 kb with a tissue distribution consistent with A1AR binding. Subcloning of the cDNA in a pCMV5 expression vector with subsequent transfection into both COS7 and Chinese hamster ovary cells revealed a fully functional A1AR which could inhibit adenylylcyclase and retained the unique pharmacologic properties of the bovine brain A1AR. The A1AR was found to have a single histidine residue in each of transmembrane domains 6 and 7. Histidine residues have been postulated by biochemical studies to be important for ligand binding. Mutation of His-278 to Leu-278 (seventh transmembrane domain) dramatically decreased both agonist and antagonist binding by greater than 90%. In contrast, mutation of His-251 to Leu 251 decreased antagonist affinity and the number of receptors recognized by an antagonist radioligand. In contrast, agonist affinity was not perturbed but the number of receptors detected by an agonist radioligand was also reduced. These data suggest that both histidines are important for both agonist and antagonist binding, but His-278 appears critical for ligand binding to occur. PMID- 1587852 TI - Modulation of the epidermal growth factor mitogenic response by metabolites of linoleic and arachidonic acid in Syrian hamster embryo fibroblasts. Differential effects in tumor suppressor gene (+) and (-) phenotypes. AB - Specific metabolites of arachidonic and linoleic acid have been proposed as serving a regulatory function in growth factor signal transduction in fibroblasts. In studies with Syrian hamster embryo (SHE) fibroblasts, we found lipoxygenase inhibitors to be potent blockers of epidermal growth factor (EGF) dependent mitogenesis. Analytical chemical characterization of arachidonic and linoleic acid metabolism in SHE cells demonstrated that the major lipoxygenase product was 13-hydroxyoctadecadienoic acid (HODE). EGF stimulation of quiescent SHE cells resulted in an enhancement of HODE biosynthesis. The primary arachidonate products were prostaglandin E2 and F2 alpha formed via the cyclooxygenase pathway. Inhibition of cyclooxygenase activity did not alter the EGF-mitogenic response in SHE cells. Addition of lipoxygenase-derived linoleate metabolites (10(-10)-10(-6) M) produced a 2-4-fold potentiation of EGF-stimulated [3H]thymidine incorporation in SHE cells. Interestingly, the linoleate products did not enhance the EGF mitogenic effect in variant SHE cells that had lost tumor suppressor gene function. These results were confirmed by autoradiographic studies of DNA synthesis and suggest that loss of tumor suppressor phenotype correlates with a lack of responsiveness to linoleate products in signal transduction. In studies on the mechanism of EGF regulation of linoleic acid metabolism, inhibitors of EGF receptor tyrosine kinase activity were observed to block EGF-stimulated HODE biosynthesis. In addition, both cyclohexamide and actinomycin D attenuated the ability of EGF to increase linoleic acid metabolism in SHE cells. EGF induction of the linoleate pathway appears to be linked to activation of the EGF receptor and may be modulated at transcriptional or translational levels. PMID- 1587853 TI - Phosphorylation of rap1GAP in vivo and by cAMP-dependent kinase and the cell cycle p34cdc2 kinase in vitro. AB - rap1GAP is a GTPase activating protein that specifically stimulates the GTP hydrolytic rate of the ras-related protein p21rap1.rap1GAP undergoes post translational modification that causes a substantial change in its mobility on sodium dodecyl sulfate-polyacrylamide gels. At least part of this modification is due to the phosphorylation. Expression of a rap1GAP cDNA in insect cells labeled with 32Pi resulted in high level incorporation of radioactivity into serine residues of the expressed protein. Purified rap1GAP was phosphorylated in vitro by cAMP-dependent kinase and the cell cycle p34cdc2 kinase. The molar ratio of incorporated phosphate/rap1GAP was approximately 3 by cAMP-dependent kinase and 2 by p34cdc2. The sites of phosphorylation by both kinases were localized to a 100 residue segment contained in the carboxyl-terminal region of the predicted primary structure of rap1GAP. Highly favorable recognition sequences for the two kinases are contained within this fragment and are proposed as the sites of phosphorylation. Treatment of SK-MEL-3 cells with dibutyryl cAMP promoted phosphorylation of rap1GAP in vivo. Based on the results of comparative phosphopeptide mapping the sites of phosphorylation in vivo and in vitro are identical. PMID- 1587854 TI - Interactions between T4 phage-coded deoxycytidylate hydroxymethylase and thymidylate synthase as revealed with an anti-idiotypic antibody. AB - Anti-idiotypic antibodies were used to mimic the binding surface of the T4 bacteriophage deoxycytidylate hydroxymethylase enzyme, providing an immunological probe for protein-protein interactions involving this enzyme. Polyclonal dCMP hydroxymethylase antibodies were affinity-purified and used to generate anti idiotypic antibodies. The anti-idiotypic serum immunoprecipitated two native viral proteins, deoxycytidylate hydroxymethylase (EC 2.1.2.8) and thymidylate synthase (EC 2.1.1.45), from a sonicated detergent-treated extract of T4-infected Escherichia coli. The anti-anti-dCMP hydroxymethylase antibody was found to be specific in binding to the T4 dTMP synthase, with no detectable affinity for the host dTMP synthase. Previous work in our laboratory has demonstrated the viral dCMP hydroxymethylase and dTMP synthase to be associated in a deoxyribonucleotide synthetase enzyme complex. Our current approach, using anti-idiotypic antibodies as probes for protein-protein interactions, and complementary studies involving dCMP hydroxymethylase enzyme affinity columns indicate a direct association between bacteriophage T4 dCMP hydroxymethylase and dTMP synthase. PMID- 1587855 TI - Identification of invariant surface glycoproteins in the bloodstream stage of Trypanosoma brucei. AB - Surface proteins of the mammalian stage of the parasitic protozoan, Trypanosoma brucei, were biotinylated with sulfosuccinimidyl 6-(biotinamido) hexanoate. Since the predominant protein labeled by this reagent is the membrane form of the variant surface glycoprotein (mfVSG), a procedure was developed to convert mfVSG to its soluble form by the endogenous glycosylphosphatidylinositol-specific phospholipase C while retaining other biotinylated surface proteins in a membrane bound state. From these membranes, three novel glycoproteins of 60, 65, and 75 kDa could be isolated by a combination of Triton X-114 phase separation and precipitations by streptavidin and concanavalin A coupled to solid supports. These polypeptides were detected in trypanosomes expressing different mfVSGs and are thus considered to be invariant. In a variant clone in which the mfVSG is trypsin-sensitive, the invariant surface glycoproteins of 65 and 75 kDa, designated ISG65 and ISG75, respectively, were proteolytically degraded with similar kinetics as the mfVSG. Neither ISG65 nor ISG75 could be detected in procyclic trypanosomes, the stage of the parasite characteristic for the insect midgut. Gene cloning reported in the accompanying paper (Ziegelbauer, K., Multhaup, G., and Overath, P. (1992) J. Biol. Chem. 267, 10797-10803) suggests that ISG65 and ISG75 are transmembrane proteins. PMID- 1587856 TI - Molecular characterization of two invariant surface glycoproteins specific for the bloodstream stage of Trypanosoma brucei. AB - In the accompanying paper (Ziegelbauer, K., and Overath, P. (1992) J. Biol. Chem. 267, 10791-10796), two invariant surface glycoproteins, ISG65 and ISG75, were identified in the mammalian stage of the parasitic protozoan, Trypanosoma brucei. In this study, the genes coding for these proteins have been isolated. Their nucleotide sequence suggests no relationship to other known genes and predicts polypeptides with NH2-terminal signal sequences, hydrophilic extracellular domains, single trans-membrane alpha-helices, and short cytoplasmic domains. ISG65 and ISG75 are expressed in bloodstream forms (70,000 and 50,000 molecules/cell, respectively) but not in the insect midgut stage. They can be detected in all T. brucei brucei variant clones investigated. Both polypeptides are distributed over the entire surface of the parasite. PMID- 1587857 TI - Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. AB - The gene for the beta A4-amyloid precursor protein (APP) consists of 19 exons which code for a typical N- and O-glycosylated transmembrane protein with four extracellular domains followed by the transmembrane domain and a short cytoplasmic domain. The beta A4-amyloid sequence is part of exons 16 and 17. Several APP isoforms can be generated by alternative splicing of exons 7 and 8, encoding domains with homologies to Kunitz-type protease inhibitors and the MRC OX-2 antigen, respectively. The mechanism by which the pathological beta A4 is generated is unknown, it is however a critical event in Alzheimer's disease and is distinct from the normally occurring cleavage and secretion of APPs within the beta A4 sequence. We report here for the first time considerable APP mRNA expression by rat brain microglial cells. In addition we showed by S1 nuclease protection and polymerase chain reaction analysis of reverse transcribed RNA (RT PCR) that T-lymphocytes, macrophages, and microglial cells expressed a new APP isoform by selection of a novel alternative splice site and exclusion of exon 15 of the APP gene. This leads to a transmembrane, beta A4 sequence containing APP variant, lacking 18 amino acid residues close to the amyloidogenic region. The use of this novel alternative splice site alters the structure of APP in close proximity to the beta A4 region and thus may determine a variant, potentially pathogenic processing of leukocyte-derived APP in brain. PMID- 1587858 TI - Alternative splicing of human prostaglandin G/H synthase mRNA and evidence of differential regulation of the resulting transcripts by transforming growth factor beta 1, interleukin 1 beta, and tumor necrosis factor alpha. AB - Prostaglandin G/H synthase (PGG/HS) is the rate-limiting enzyme in the conversion of arachidonic acid to prostaglandins and thromboxanes. We screened a human lung fibroblast cDNA library with an ovine PGG/HS cDNA and isolated a 2.3-kilobase clone (HCO-T9). Sequence analysis of this clone showed that (a) it contained the entire translated region of PGG/HS and (b) it displayed an in-frame splicing of the last 111 base pairs encoded by exon 9, which resulted in the elimination of the N-glycosylation site at residue 409. Polymerase chain reaction amplification with specific oligonucleotides of reverse-transcribed mRNA from diverse human tissues and cultured cells yielded 400- and 300-base pair fragments that corresponded, respectively, to the intact and spliced transcripts. The expression of these two transcripts in cultured human lung fibroblasts was differentially regulated by serum, transforming growth factor beta 1, interleukin 1 beta, tumor necrosis factor alpha, and phorbol 12-myristate 13-acetate, as each of these conditions stimulated preferentially the expression of the unspliced transcripts. The elimination of one of the four N-glycosylation sites by the alternative splicing of exon 9 and the differential regulation of this process by relevant cytokines and growth factors may represent a mechanism for the regulation of PGG/HS enzymatic activity under physiological or pathological conditions. PMID- 1587859 TI - Role of conserved and nonconserved residues in the Ca(2+)-dependent carbohydrate recognition domain of a rat mannose-binding protein. Analysis by random cassette mutagenesis. AB - The carbohydrate-recognition domain of rat serum mannose-binding protein A has been subjected to random cassette mutagenesis. Mutant domains, expressed in bacteria, were initially screened for binding to invertase-coated nitrocellulose and then analyzed further for Ca2+ affinity, saccharide binding, resistance to proteolysis, and oligomerization. The results are consistent with previous evolutionary and structural studies. Six out of seven completely inactive mutants have changes in residues directly involved in ligating Ca2+. Most changes in conserved residues which form part of the hydrophobic core characteristic of Ca(2+)-dependent (C-type) animal lectins result in decreased affinity for Ca2+, even though these residues are distant from the Ca2+ sites. Changes can be made in large portions of the surface without affecting saccharide binding. The results indicate that the precise arrangement of the regular portion of the domain containing the hydrophobic core is necessary for formation of a stable Ca(2+)-ligated structure under physiological conditions. The data also suggest that the saccharide-binding site is likely to be in close proximity to the bound Ca2+. PMID- 1587860 TI - Structural and thermodynamic analysis of compensating mutations within the core of chicken egg white lysozyme. AB - High resolution crystal structures have been determined for six chicken-type lysozymes that were constructed to investigate putative intermediates in the evolution of the lysozymes of modern game birds (Malcolm, B. A., Wilson, K. P., Matthews, B. W., Kirsch, J. F., and Wilson, A. C. (1990) Nature 345, 86-89). The amino acid replacements include Thr-40----Ser, Ile-55----Val, and Ser-91----Thr, as well as combinations of these substitutions. Residues 40, 55, and 91 are buried within the core of chicken lysozyme. The replacements therefore involve the insertion and/or removal of methyl groups from the protein interior. The mutant proteins have normal activities, and their thermal stabilities span a range of 7 degrees C, with some variants more stable and some less stable than the naturally occurring forms. Comparison of the crystal structures shows the overall structures to be very similar, but there are differences in the packing of side chains in the region of the replacements. The x-ray coordinates were used to evaluate the repacking of side chains in the protein interior and to attempt to evaluate the contributions of the different energetic interactions toward the overall stability of each variant. The results illustrate how proteins can compensate for potentially destabilizing substitutions in different ways and underscore the importance of high resolution structural data if changes in protein thermostability due to changes in protein sequence are to be understood. The findings also suggest that protein stability can be increased by mutations that lower strain in the protein interior while maintaining total buried hydrophobic surface area. PMID- 1587861 TI - Recognition sites for clathrin-associated proteins AP-2 and AP-3 on clathrin triskelia. AB - AP-2 and AP-3 are cellular proteins that drive the in vitro polymerization of clathrin triskelia into cage structures. The interaction of these two types of assembly proteins (APs) with preassembled clathrin cages has been studied in order to identify the sites on the triskelia required for binding. Comparing binding of the APs to intact or to proteolytically clipped cages, we attempted to distinguish between binding to the terminal domain, the globular end of the heavy chain, and binding to the hub of the clathrin triskelia, the portion that remains assembled after trypsin treatment. AP-3 binds to intact clathrin cages but not to those that were treated with trypsin. AP-3 also bound to cages consisting solely of clathrin heavy chains; proteolysis of these cages also eliminated AP-3 binding. In addition, AP-3 did not bind to either isolated hubs or terminal domains that had been immobilized on Sepharose. These data indicate that clathrin light chains are not required for binding of AP-3, and that neither terminal domain nor hubs alone will suffice. However, an intact heavy chain is both necessary and sufficient for the binding of AP-3. Previous work has demonstrated one binding site for AP-2 on proteolyzed cages containing only clathrin hubs; the existence of a second binding site associated with the terminal domain was hypothesized. Here we provide direct evidence for recognition by AP-2 of isolated terminal domains immobilized on Sepharose and show that the core of the AP-2 molecule is responsible for this interaction. These results provide the first demonstration of a functional role for the conserved terminal domain of the clathrin heavy chain. PMID- 1587862 TI - Sequencing, cloning, and expression of human red cell-type acid phosphatase, a cytoplasmic phosphotyrosyl protein phosphatase. AB - Low molecular weight phosphotyrosyl protein phosphatases of human placenta and human red cell were purified and sequenced by a combination of Edman degradation and tandem mass spectrometry. Screening of a human placental lambda gt11 cDNA library yielded overlapping cDNA clones coding for two distinct human cytoplasmic low molecular weight phosphotyrosyl protein phosphatases (HCPTPs). The two longest clones, designated HCPTP1-1 and HCPTP2-1, were found to have identical nucleotide sequences, with the exception of a 108-base pair segment in the middle of the open reading frame. Polymerase chain reaction studies with human genomic DNA suggest that the difference between HCPTP1-1 and HCPTP2-1 does not result from alternative RNA splicing. Studies with a human chromosome 2-specific library confirmed that these sequences are located on chromosome 2, which is known to be the location of red cell acid phosphatase locus ACP1. The coding sequences of HCPTP1-1 and HCPTP2-1 were placed downstream from a bacteriophage T7 promoter and the proteins were expressed in Escherichia coli. The resulting recombinant enzymes (designated HCPTP-A and HCPTP-B, respectively) showed molecular weights of 18,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and both of them exhibited immunoreactivity with antisera raised against authentic human placental and bovine heart enzymes. The expressed proteins were highly active towards the phosphatase substrates p-nitrophenyl phosphate, beta-naphthyl phosphate, and O-phospho-L-tyrosine, but not alpha-naphthyl phosphate, threonine phosphate, or O-phospho-L-serine. HCPTP-A and -B possessed effectively identical amino acid compositions, immunoreactivities, inhibition by formaldehyde, and kinetic properties when compared with two human red cell acid phosphatase isoenzymes. It is concluded that HCPTP-A and -B are the fast and slow forms of red cell acid phosphatase, respectively, and that this enzyme is not unique to the red cell but is instead expressed in all human tissues. PMID- 1587863 TI - T double-stranded RNA (dsRNA) sequence reveals that T and W dsRNAs form a new RNA family in Saccharomyces cerevisiae. Identification of 23 S RNA as the single stranded form of T dsRNA. AB - Some strains of the yeast Saccharomyces cerevisiae harbor a double-stranded RNA (dsRNA) molecule, called T. We obtained T cDNA clones by random priming of denatured T dsRNA followed by reverse transcription. Sequence data of T show that only one strand ((+)-strand) has coding capacity for a protein with 940 amino acids which spans almost the entire length of the molecule (2.9 kilobases). Within this protein we found a sequence pattern characteristic of RNA-dependent RNA polymerases of (+)-strand and double-stranded RNA viruses. Although T has no homology with other dsRNAs found in S. cerevisiae, such as L-A, L-BC, M1, or W, the T-encoded protein shows a high degree of conservation with the W-encoded protein. This conservation extends beyond a region that contains the consensus sequences for RNA-dependent RNA polymerases, suggesting that both T and W are evolutionarily related. With a (+)-strand-specific probe for T we identified 23 S RNA, a new single-stranded RNA (ssRNA) species with a sedimentation coefficient of 23 S. T and 23 S RNA have the same mobility under denaturing conditions with glyoxal, suggesting that 23 S RNA is, in fact, the (+)-single-stranded RNA form of T dsRNA. 23 S RNA synthesis is induced under stress conditions such as heat shock and starvation. The relationship between T and 23 S RNA clearly resembles the one between W and its single-stranded derivative form, 20 S RNA. Thus T and W dsRNAs (and their respective single-stranded species) constitute a new RNA family in S. cerevisiae. PMID- 1587864 TI - A limiting factor mediates the differential activation of promoters by the human progesterone receptor isoforms. AB - The two transcription activation functions (TAFs) of the human progesterone receptor (hPR) have been characterized. TAF-1, located in the N-terminal region A/B, has been narrowed down to a 91-amino acid sequence, which is sufficient for transcription activation in chimeras with the GAL4 DNA binding domain. Both hPR TAF-1 and TAF-2 activate a minimal promoter in yeast. No autonomous TAF could be found in the N-terminal 164 amino acids (designated AB3) which are responsible for the differential activation of promoters by the hPR isoforms A and B. Reduction of the target gene promoter complexity did not alter this differential activation, indicating that AB3 does not require additional promoter-bound factors to exert its effect. Instead, the cell specificity of AB3 and its ability to squelch hPR-induced transcription suggest that this differential isoform activity is due to the effect of a limiting factor which binds to region AB3. PMID- 1587865 TI - Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. AB - From bovine brain microtubules we purified tau protein kinase I (TPKI, Mr 45,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tau protein kinase II (TPKII) whose activity was attributed to a 30-kDa protein on SDS-PAGE by affinity-labeling using an ATP analog. Both kinases were activated by tubulin. TPKII, but not TPKI, phosphorylated tau fragment peptides previously used for detection of a Ser/ThrPro kinase activity. Therefore, TPKII was considered to be the Ser/ThrPro kinase. TPKI was more effective than TPKII for producing the decrease of tau-1 immunoreactivity and mobility shift of tau on SDS PAGE. Moreover, TPKI, but not TPKII nor other well-known protein kinases, generated an epitope present on paired helical filaments. These findings suggested that tau phosphorylated by TPKI resembled A-68, a component of paired helical filaments. PMID- 1587867 TI - Preincubation of T antigen with DNA overcomes repression of SV40 DNA replication by nucleosome assembly. AB - Circular duplex DNA containing the SV40 replication origin was assembled into chromosomes in vitro with core histones and nucleosome assembly factor from HeLa cells. Their ability to serve as a template for replication was examined by incubating them with SV40 T antigen and HeLa cell extract. Nucleosome assembly of the template prevented DNA replication. Replication of chromosomes was severely inhibited at more than two-thirds of physiological nucleosome density. When the DNA was preincubated with T antigen and then assembled into chromosomes, however, inhibition of DNA replication was greatly reduced. These results suggest that nucleosome assembly of the template inhibits initiation of SV40 DNA replication and that the inhibition can be overcome by formation of an initiation complex before nucleosome assembly. PMID- 1587866 TI - Functional expression of the alpha-hemolysin of Staphylococcus aureus in intact Escherichia coli and in cell lysates. Deletion of five C-terminal amino acids selectively impairs hemolytic activity. AB - The alpha-hemolysin gene from Staphylococcus aureus, excluding the 5' region encoding the hydrophobic leader sequence, was amplified from genomic DNA. The identity of the disputed C terminus has been confirmed and revisions made to the internal sequence. The hemolysin is expressed at high levels in Escherichia coli and has been purified to homogeneity from this source. In addition, active [35S Met]alpha-hemolysin of high specific radioactivity can be generated in an E. coli transcription-translation system. By criteria based on protein chemistry, and biological and electrophysiological assays, the recombinant polypeptide is closely similar to the staphylococcal polypeptide ruling out the possibility of functionally important posttranslational modifications in S. aureus. Convenient new assays utilizing the 35S-labeled polypeptide to measure erythrocyte binding, oligomer formation in detergent and on target cells, and hemolysis have been developed. They have been used to demonstrate that a deletion mutant of alpha hemolysin, in which five C-terminal amino acids are absent, is severely compromised in its ability both to oligomerize and to lyse rabbit erythrocytes. The mutant polypeptide nevertheless binds tightly to erythrocytes as a monomer, strengthening the idea that oligomerization is required for cell lysis. PMID- 1587868 TI - Role of the amino-terminal domain of bacteriophage phi 29 connector in DNA binding and packaging. AB - The connector of bacteriophage phi 29 is required for prohead assembly, binds DNA, and drives DNA packaging into viral proheads. Limited proteolysis of the connector protein with endoproteinase Glu-C from Staphylococcus aureus V8 and chymotrypsin showed that a domain of the NH2-terminal region is involved in DNA binding and in the subsequent packaging into preformed proheads, but not in prohead assembly. Mutants in specific amino acids of the NH2-terminal domain, obtained by directed mutagenesis techniques, showed that the Ala1-Arg2-Lys3-Arg4 region of the connector is absolutely necessary for DNA packaging into the proheads as well as for efficient DNA binding. PMID- 1587869 TI - The Gamma nail--a significant advance or a passing fashion? PMID- 1587870 TI - Ceramic hips. PMID- 1587871 TI - Ionising radiation and the orthopaedic surgeon. PMID- 1587872 TI - Iatrophysics to biomechanics. From Borelli (1608-1679) to Pauwels (1885-1980). PMID- 1587873 TI - The Gamma nail for peritrochanteric fractures. AB - The Gamma nail was designed to treat unstable intertrochanteric and subtrochanteric fractures. The device was developed after cadaver studies and has been used clinically since February 1985 in a total of 421 patients. The results in 123 patients treated by the third version of this design are reported. The Gamma nail transmits weight closer to the calcar than does the dynamic hip screw and it has greater mechanical strength. A semi-closed operative technique is used, with an average duration of operation of 35 minutes and little blood loss. Distal locking screws can be used to maintain rotational stability, and can be inserted without the use of an image intensifier. Results showed satisfactory fracture union with little loss of position, even in comminuted fractures. Operative complications were few, but included fractures of the base of the greater trochanter. The most important postoperative complication, seen in one case, was fracture of the shaft of the femur at the distal end of the nail, but this healed well after re-nailing. PMID- 1587874 TI - Gamma nails and dynamic hip screws for peritrochanteric fractures. A randomised prospective study in elderly patients. AB - The Gamma nail was introduced for the treatment of peritrochanteric fractures with the theoretical advantage of a load-sharing femoral component which could be implanted by a closed procedure. We report a randomised prospective study of 186 fractures treated by either the Gamma nail or a dynamic hip screw. Gamma nails were implanted with significantly shorter screening times, smaller incisions, and less intraoperative bleeding. The Gamma nail group had a shorter convalescence and earlier full weight-bearing, but there was no significant difference in mortality within six months, postoperative mobility, or hip function at review. More intra-operative complications were recorded in the Gamma nail group, mainly due to the mismatching of the femoral component of the nail to the small femurs of Chinese people. Use of a smaller modified nail reduced these complications. We conclude that with careful surgical technique and the modified femoral component, the Gamma nail is an advance in the treatment of peritrochanteric fractures. PMID- 1587875 TI - A biomechanical evaluation of the Gamma nail. AB - We examined the effect of the Gamma nail on strain distribution in the proximal femur, using ten cadaver femora instrumented with six unidirectional strain gauges along the medial and lateral cortices. The femora were loaded to 1800 N and strains were determined with or without distal interlocking screws before and after experimentally created two-part and four-part fractures. Motion of the sliding screw and the nail was also determined. Strain patterns and screw motion were compared with previously obtained values for a sliding hip screw device (SHS). The Gamma nail was shown to transmit decreasing load to the calcar with decreasing fracture stability, such that virtually no strain on the bone was seen in four-part fractures with the posteromedial fragment removed; increasing compression was noted, however, at the proximal lateral cortex. Conversely, the SHS showed increased calcar compression with decreasing fracture stability. The insertion of distal interlocking screws did not change the pattern of proximal femoral strain. The Gamma nail imparts non-physiological strains to the proximal femur, probably because of its inherent stiffness. These strains may alter bone remodelling and interfere with healing. Distal interlocking screws may not be necessary for stable intertrochanteric fractures. PMID- 1587876 TI - Locked nailing for nonunion of the tibia. AB - We treated 24 patients with nonunion of tibial shaft fractures by locked intramedullary nailing, 18 by open and six by closed techniques. Union was achieved in 22 patients, failing only in two patients with active infection. Locked nailing prevented recurrence of deformity and allowed the patients to mobilise without external support. Supplementary bone grafting was essential only for major defects. PMID- 1587877 TI - The floating shoulder: ipsilateral clavicle and scapular neck fractures. AB - In ipsilateral mid-clavicular and scapular-neck fractures, the mechanical stability of the suspensory structures is disrupted and muscle forces and the weight of the arm pull the glenoid fragment distally and anteromedially. To prevent late deformity we recommend internal fixation of the fractured clavicle by a plate and screws. We treated seven patients with this unusual injury; all achieved an excellent functional result without deformity. PMID- 1587878 TI - Tibial nerve mistakenly used as a tendon graft. Reports of three cases. AB - We describe three patients in whom the tibial nerve was used, in mistake for the plantaris tendon, to repair a ruptured calcaneal tendon. The tendon repair was successful in all cases, but despite attempted reconstruction of the nerve, no patient had any motor recovery although two regained some protective sensation. PMID- 1587879 TI - Hip arthroplasty in patients with sickle-cell haemoglobinopathy. AB - We reviewed retrospectively 25 hip arthroplasties in 25 patients with sickle-cell haemoglobinopathy and osteonecrosis. The mean age of the ten women and 15 men at the onset of hip symptoms was 25 years, and at surgery 30 years (16 to 45); 66% had either SS or S-thal disease, 20% sickle-cell trait, and the remainder SC disease. The mean follow-up was 8.6 years (two to 18). Fourteen (40%) of the arthroplasties had been revised at a mean of 7.5 years after the primary procedure and nine other hips were either radiographically and/or symptomatically loose. The overall complication rate was 49% and the infection rate 20%. The risk to-benefit ratio of hip arthroplasty in sickle-cell haemoglobinopathy is high. PMID- 1587880 TI - The initial stability of uncemented acetabular components. AB - The osseo-integration of an uncemented acetabular component depends on its initial stability. This is usually provided by under-reaming of the acetabulum. We have assessed the fixation of 52 mm porous-coated hemispherical prostheses inserted into cadaveric acetabula under-reamed by 1, 2, 3 and 4 mm. We tested the torsional stability of fixation, after preloading with 686 N in compression, by measuring the torque required to produce 1 degree and 2 degrees of rotation. Under-reaming by 2 mm and 3 mm gave significantly better fixation than 1 mm (p less than 0.01, p less than 0.02). Insertion after under-reaming of 4 mm caused some fractures. To obtain maximum interference fit and optimal implant stability, we recommend the use of an implant 2 mm or 3 mm larger than the last reamer. PMID- 1587881 TI - Impingement and loosening of the long posterior wall acetabular implant. AB - Long posterior wall (LPW) Charnley acetabular implants are widely used as it is believed that the LPW helps to prevent dislocation. This has, however, not been proven statistically. In a preliminary study of these implants removed at revision marked erosion of the LPW was frequently seen, indicating that repetitive impingement may occur. The influence of the long posterior wall was therefore investigated mathematically. LPW and standard sockets were found to be equally likely to dislocate provided that the standard socket was anteverted 5 degrees more than the LPW socket. With simulated external rotation, LPW sockets impinge 30% earlier than standard sockets. When impingement occurs a torque is applied to the components, which increases the shear stresses at the cement-bone interface. The torques, although not large enough to dislodge the socket immediately, are repetitive and so may contribute to loosening. The LPW socket can generate twice as much torque as the standard socket and therefore is more likely to loosen. PMID- 1587882 TI - Size of metallic and polyethylene debris particles in failed cemented total hip replacements. AB - Reports of differing failure rates of total hip prostheses made of various metals prompted us to measure the size of metallic and polyethylene particulate debris around failed cemented arthroplasties. We used an isolation method, in which metallic debris was extracted from the tissues, and a non-isolation method of routine preparation for light and electron microscopy. Specimens were taken from 30 cases in which the femoral component was of titanium alloy (10), cobalt-chrome alloy (10), or stainless steel (10). The mean size of metallic particles with the isolation method was 0.8 to 1.0 microns by 1.5 to 1.8 microns. The non-isolation method gave a significantly smaller mean size of 0.3 to 0.4 microns by 0.6 to 0.7 microns. For each technique the particle sizes of the three metals were similar. The mean size of polyethylene particles was 2 to 4 microns by 8 to 13 microns. They were larger in tissue retrieved from failed titanium-alloy implants than from cobalt-chrome and stainless-steel implants. Our results suggest that factors other than the size of the metal particles, such as the constituents of the alloy, and the amount and speed of generation of debris, may be more important in the failure of hip replacements. PMID- 1587883 TI - Improved cementing techniques and femoral component loosening in young patients with hip arthroplasty. A 12-year radiographic review. AB - To assess the effect of improved methods of femoral cementing on the loosening rates in young patients, we reviewed 50 'second-generation' cemented hip arthroplasties in 44 patients aged 50 years or less. The femoral stems were all collared and rectangular in cross-section with rounded corners. The cement was delivered by a gun into a medullary canal occluded distally with a cement plug. A clinical and radiographic review was undertaken at an average of 12 years (10 to 14.8) and no patient was lost to follow-up. No femoral component was revised for aseptic loosening, and only one stem was definitely loose by radiographic criteria. By contrast, 11 patients had undergone revision for symptomatic aseptic loosening of the acetabular component and 11 more had radiographic signs of acetabular loosening. PMID- 1587884 TI - Leg oedema due to a rheumatoid cyst in the pelvis. AB - We describe a case in which chronic oedema of a leg was due to pressure on the external iliac vein from an intrapelvic rheumatoid cyst. Ultrasound and CT scanning gave the clues to diagnosis. PMID- 1587885 TI - Allograft reconstruction in total knee arthroplasty. AB - We reviewed 32 deep-frozen irradiated allografts used for the reconstruction of bone defects in 20 knees. They were subdivided into bulk grafts, cortical strut grafts, and morsellised bone. The average follow-up was 4.2 years (2 to 7.2). Radiographs showed union of the allograft to the host in all cases. Two allografts later fractured and three knees required further surgery because of infection. The allografts effectively filled large bone defects around the knee, lessening the need for custom-made and constrained prostheses. PMID- 1587886 TI - The bacteriology of bone allografts. AB - We report the contamination rate in the Cambridge bone bank of 35 consecutive allograft specimens, all harvested in a clean-air environment, using a strict aseptic technique and antibiotic cover. Five of 27 femoral heads taken from living donors and three of eight massive allografts taken from cadavers were found to be contaminated. The contaminated femoral heads were discarded. All massive allografts were rendered sterile by gamma-irradiation. It is important to exclude bacteriological contamination of harvested and banked bone. PMID- 1587887 TI - Primary knee arthroplasty for distal femoral fractures in elderly patients. AB - We discuss the role of primary knee arthroplasty in supracondylar and intercondylar fractures of the femur in elderly patients with reference to 13 cases. This method of treatment is shown to be effective and to have good results. It is recommended for all type C and some type A supracondylar fractures in old people. PMID- 1587888 TI - The natural history of the meniscus in anterior cruciate insufficiency. Arthroscopic analysis. AB - We studied arthroscopically the meniscal pathology in 100 patients with functional instability of the knee from isolated rupture of the anterior cruciate ligament at an average time of three years after injury. Meniscal tears were observed in 86 patients and multiple lesions of both menisci were common. An incomplete longitudinal cleavage, visible on both surfaces of the posterior horn, was seen in more than half the knees and seemed to indicate progressive meniscal deterioration. Clinical examination was unreliable and we suggest that arthroscopic assessment is necessary for accurate diagnosis and staging. PMID- 1587889 TI - Bilateral femoral shortening for unaccepted tallness. AB - We performed bilateral femoral shortening operations on 15 skeletally mature patients (11 women and four men). Their mean height pre-operatively was 193.5 cm and they were shortened by 5 to 9 cm. We used a subtrochanteric Z-osteotomy with an AO condylar plate in 11 patients, and mid-diaphyseal osteotomy with an intramedullary locking nail in four. After an average follow-up of 8.1 years, isokinetic muscle testing showed that muscle strength was reduced bilaterally in five patients. The strength ratio between hamstrings and quadriceps muscles was normal in all those treated by subtrochanteric shortening; in those shortened at the mid-shaft the quadriceps was relatively weaker. The result was rated as excellent by 11 patients, very good by three, and good by one. PMID- 1587890 TI - Primary degenerative arthritis of the elbow. Treatment by ulnohumeral arthroplasty. AB - Degenerative arthritis of the elbow is a poorly recognised condition, usually seen in a middle-aged man with an occupation or activity which involves the repetitive use of his dominant arm. Flexion contracture and pain at terminal extension are common presenting features. Fifteen patients were reviewed at a mean of 33 months after debridement by ulnohumeral arthroplasty. Fourteen had good relief of pain, elbow extension had improved by an average of 11 degrees and elbow flexion by 10 degrees. On an objective scale 12 of the 15 patients had good or excellent results and 13 (87%) felt that they were improved by the operation. PMID- 1587891 TI - Clinical diagnosis of tears of the rotator cuff. AB - We have studied the reported clinical assessment of the presence and extent of a rotator cuff tear in 42 patients presenting to a special shoulder clinic. This pre-operative diagnosis was compared with the findings at operation. The clinical tests had a sensitivity of 91% and a specificity of 75%. It is important to exploit clinical examination before resorting to costly and sometimes harmful special investigations. PMID- 1587892 TI - Rolando's fracture of the first metacarpal. Treatment by external fixation. AB - External fixation of the first metacarpal was used in Rolando's fracture to counter the forces that cause shortening and articular incongruity. Satisfactory reduction was achieved and maintained in five patients. PMID- 1587893 TI - Closed division of the flexor tendon sheath for trigger finger. AB - Closed tenotomy was used to treat triggering of the fingers and thumb in 54 patients. In 56 digits the method was successful; in seven it was a simple matter to proceed to open tenotomy. With experience, the closed procedure can be completed within minutes without risk of damaging the digital nerves. PMID- 1587894 TI - Spinal abnormalities in young fast bowlers. AB - The action of fast bowling in the game of cricket is known to cause injuries to the lumbar spine. We studied a group of 16- to 18-year-old fast bowlers, selected for special training in Western Australia. All 24 had MR scans of the spine, 22 had radiographs and CT scans; in 20 the bowling technique was analysed biomechanically. There was a high incidence of back pain and this was always associated with a radiological abnormality. Pars interarticularis defects were diagnosed in 54% and intervertebral disc degeneration in 63%. Bowling actions which involved counter-rotation were associated with a higher incidence of both injuries. PMID- 1587895 TI - The Scott wiring technique for direct repair of lumbar spondylolysis. AB - Between 1979 and 1989, we treated 22 patients with symptomatic lumbar spondylolysis which had not responded to conservative treatment by a modified Scott wiring technique to give direct repair of the lytic defects with stabilisation. The patients' mean age at the time of operation was 15 years; the mean follow-up period was four years. All 19 patients under 25 years old had satisfactory results. Two of the three patients over 25 years old had poor results. The age of the patient at surgery seems to be an important determinant of outcome. Radiologically confirmed fusion is of secondary importance. The presence of a grade I spondylolisthesis did not prejudice the result. We recommend the Scott wiring technique to stabilise the direct repair of a lumbar spondylolysis. PMID- 1587896 TI - MRI and discography of annular tears and intervertebral disc degeneration. A prospective clinical comparison. AB - We attempted to correlate the findings of MRI and discography in patients with low back pain, examining 108 lumbar intervertebral discs in 33 consecutive patients. MRI results were assessed from the intensity and shape of the signal obtained from the central part of the disc. Discography was classified according to the pattern of contrast material, the pressure accepted and the pain reproduced. All discs which were abnormal on MRI had altered patterns on discography, but 18 of the 60 discs with normal MRI had abnormal discograms. Of 39 asymptomatic discs, 33 had normal MRI signals and 24 had normal discograms. None of the 15 discs showing severe degeneration on MRI sustained high levels of intradiscal pressure, but only six of the 60 discs giving normal MRI had low pressure. With current techniques, discography is more accurate than MRI for the detection of annular pathology: a normal MRI does not exclude significant changes in the peripheral structure of the intervertebral disc which can produce low back pain. PMID- 1587897 TI - Treatment of the missed Monteggia fracture in the child. AB - Eight children with missed Monteggia fracture-dislocations are described. Seven had reconstructive surgery which included resection of scar tissue from the radiohumeral joint, proximal ulnar osteotomy, reduction of the radial head and reconstruction of the annular ligament. One had excision of the radial head. Excellent results were obtained in patients under ten years of age, up to four years after the initial injury. PMID- 1587898 TI - Foot deformities in diastrophic dysplasia. An analysis of 102 patients. AB - The exceptionally high prevalence of diastrophic dysplasia in Finland has enabled us to analyse the foot deformities of 102 patients at their first orthopaedic evaluation and classify 204 feet into five categories. The most common finding (43%) was a foot with tarsal valgus deformity and metatarsus adductus; 37% showed either equinovarus adductus (29%) or equinus (8%) deformities. At the first examination 13% showed metatarsus adductus deformity alone, and 7% were clinically normal. The expression 'club foot', generally used for the foot deformity in diastrophic dysplasia is a misnomer. There is a wide spectrum of deformities, some of them specific for the condition. PMID- 1587899 TI - Dillwyn Evans operation for relapsed club foot. Long-term results. AB - We reviewed the long-term results of the Dillwyn Evans procedure for club foot in 60 feet of 45 patients with an average age of 29 years, using four different scoring systems. The results at 12 to 38 years were compared with those of an earlier study of the same group of patients. Function was satisfactory in 68% of feet; 90% of the patients were able to perform all desired activities. Mild residual deformity was compatible with satisfactory function, and poor function was related to ankle and subtalar stiffness. Our results suggest that this procedure has a low rate of deterioration and degenerative change with time. PMID- 1587900 TI - Benign paroxysmal torticollis of infancy. AB - Benign paroxysmal torticollis is a self-limiting condition occurring during infancy. It resolves by the age of two to three years. Periodic episodes of torticollis may randomly alternate from side to side and be associated with other symptoms. The aetiology is unknown and no treatment is effective. It is relatively uncommon, and has not been previously reported in the orthopaedic literature, although initial referral may well be to an orthopaedic surgeon. We report four cases, and review the literature. PMID- 1587901 TI - Hydroxyapatite coating on carbon composite hip implants in dogs. AB - In 33 dogs we implanted femoral stems made either of carbon composite, some coated with hydroxyapatite, or of titanium alloy with a porous coating. Osseointegration was greater in the hydroxyapatite-coated than in the un-coated stems (p less than 0.001). Push-out tests, at an average of 7.2 months after implantation, showed a six-fold increase in interface shear strength and a twelve fold increase in shear stiffness in the hydroxyapatite-coated group compared with noncoated implants. The highest shear-strength values were found in the porous coated titanium alloy stems, around which there was also the most resorptive bone remodelling. PMID- 1587902 TI - Experimentally produced fractures of articular cartilage and bone. The effects of shear forces on the pig knee. AB - Experimental injuries of cartilage and bone were produced by applying shear force to the articular surfaces of the lateral femoral condyles of six-month-old pigs under various loading conditions. The lesions were divided into two groups, 'open' or 'closed', depending on the presence of a crack on the articular surface. Each was further divided into four types according to the depth of penetrating injury: (1) splitting of uncalcified cartilage; (2) splitting at the subchondral plate; (3) subchondral fracture; and (4) intra-articular fracture. When shear force was applied at high speed but with low energy, the articular cartilage surface was the first to crack. At low speed and low energy, splits occurred in the deeper layers first. As the energy increased, both loading conditions eventually resulted in similar open lesions. Experimentally produced shear injuries are useful models for clinical osteochondral fracture, osteochondritis dissecans, and chondromalacia patellae. PMID- 1587903 TI - Changes in the interposed capsule after Chiari osteotomy. An experimental study on rabbits with acetabular dysplasia. AB - We have investigated the changes in the interposed capsule after a Chiari pelvic osteotomy, in an experimental study on dysplastic hips in 20 adolescent rabbits. Radiographic, macroscopic and microscopic observations were made up to 12 months after operation. The new acetabular roof had incorporated the interposed capsule and remodelled completely by six months. By 12 months there was a new, stable hip with continuity between the capsule and the original acetabular cartilage. Histologically, the capsule underwent metaplastic change to fibrocartilaginous tissue after six months, with some hyaline-like cartilage near the joint surface. These changes in the interposed capsule play an important role in the formation of a new joint after a Chiari pelvic osteotomy. PMID- 1587904 TI - Idiopathic infarction of the psoas with lumbar plexus involvement. PMID- 1587905 TI - Ossification of the posterior longitudinal ligament and fluorosis. PMID- 1587906 TI - Ultrasound diagnosis of neonatal fracture separation of the upper humeral epiphysis. PMID- 1587907 TI - Patellotibial impingement in Kinemax stabilised total knee replacement. PMID- 1587908 TI - Antibiotics during dental surgery after joint replacement. PMID- 1587909 TI - Failure of acetabular cups. PMID- 1587910 TI - External fixation of intertrochanteric fractures. PMID- 1587911 TI - Anaesthesia for hip replacement. PMID- 1587913 TI - Australian and New Zealand Orthopaedic Associations. Christchurch, New Zealand, August 18-23, 1991. Abstracts. PMID- 1587912 TI - European Society for Surgery of the Shoulder and the Elbow. Wurzburg, June 6-8 1991. Abstracts. PMID- 1587914 TI - European Spine Society. Rome, Italy, October 17-19, 1991. Abstracts. PMID- 1587916 TI - Antidietary antigen antibodies in the sera of patients with burns as a potential marker of gut mucosa integrity failure. AB - It was hypothesized that a failure of gut mucosa integrity after burn injury may lead to translocation of food proteins as well as bacteria and endotoxins. Certain, normally digested proteins may stimulate the humoral immune response as they enter the circulation. To test this hypothesis, serum samples from 16 patients with burns and 10 healthy donors were tested for the presence of antigliadin and anti-beta-lactoglobulin antibodies of immunoglobulin M (IgM), IgG, IgA, and IgE classes by means of enzyme-linked immunosorbent assay. Patients and donors remained on a standard diet that included wheat (gliadin) and milk products (beta-lactoglobulin). In the group of six patients with severe burns (mean total body surface area burn = 50%), antigliadin and anti-beta lactoglobulin IgG and IgA antibodies were detected. In the control group and in 10 patients with small to moderate burns (mean total body surface area burn = 15%), these antibodies were not observed. There was a significant correlation between antigliadin IgG and IgA titers (r greater than 0.9) and anti-beta lactoglobulin antibodies (r greater than 0.7) in patients with burns. Results suggest immunization by gliadin and beta-lactoglobulin in the group of patients with severe burns. PMID- 1587915 TI - Cornification and basement membrane formation in a bilayered human skin equivalent maintained at an air-liquid interface. AB - Human keratinocytes that were grown in a skin equivalent at an air-liquid interface were analyzed morphologically and biochemically to demonstrate differentiation approaching that of human skin. Within 3 weeks of growth at the interface, cuboidal basal cells, distinct spinous and granular zones, and a fully developed cornified layer of enucleated cells formed the multilayered epidermis. Ultrastructurally, the keratinocytes in the upper granular layer contain tonofilament bundles and membrane-coating granules. These cells form cornified squames that are resistant to degradation by sodium dodecyl sulfate/dithiothreitol. Basal cells are attached to a developing basement membrane with hemidesmosomes. Immunogold silver staining analysis with monoclonal antibodies demonstrated the expression of basement membrane collagens IV and VII. This level of differentiation might improve "take" of human grafts and provides a useful system with which to study topical carcinogens and tumor promoters in vitro. PMID- 1587917 TI - Susceptibility testing of topical antibacterials against methicillin-resistant Staphylococcus aureus. AB - Methicillin-resistant Staphylococcus aureus (MRSA) isolates that were collected from 44 consecutive patients during 1 year in a community hospital were tested for susceptibility to five commonly used topical antibacterial agents. Agar-well susceptibility testing, which was based on zones of inhibition, was used to compare the effectiveness of the antibacterials against MRSA. Nitrofurazone was effective in inhibition of bacterial growth and was relatively inexpensive. Mupirocin was found to be effective but more costly for treatment of MRSA. Varying degrees of susceptibility to silver sulfadiazine, mafenide acetate, and bacitracin were noted in the cultures that were obtained at this medical center. On the basis of our findings from susceptibility tests compared with those of another center, we recommend that all hospitals undertake topical sensitivity testing of their MRSA isolates. Appropriate and effective topical antibacterial therapy can then be planned within each center. PMID- 1587918 TI - Causes and time course of acute hemolysis after burn injury in the rat. AB - Thermal injury can cause acute red blood cell damage and destruction, but the mechanisms of these effects are not well described. To investigate the red blood cell abnormalities that occur after burn injury we studied the time course of red blood cell changes that are seen early after burn injury. Male Sprague-Dawley rats were divided into control, sham-burn, and burn (30% total body surface area full-thickness) groups. Plasma-free hemoglobin, erythrocyte osmotic fragility, and red blood cell membrane deformability were measured in the first 8 hours after burn injury. Plasma-free hemoglobin was significantly increased 1 hour after injury. It fell promptly but remained significantly higher than the control value at 4 and 8 hours after burn injury. Osmotic fragility was also significantly increased when compared with control values, whereas membrane deformability was less than control values for the duration of the experiment. This study identifies an early hemolytic effect of burn injury and documents red blood cell changes in osmotic fragility and membrane deformability that may contribute to accelerated red blood cell loss later in the course of burn management. PMID- 1587919 TI - Carbon monoxide poisoning and myocardial ischemia in patients with burns. AB - Carbon monoxide poisoning is a well-known problem in patients with burns. A retrospective 11-year chart review was undertaken to determine the incidence of myocardial injury after carbon monoxide poisoning. Of the 1533 consecutive admissions from July 1, 1979 to June 30, 1990, 18 patients had carboxyhemoglobin levels of greater than or equal to 10% on admission. Five of these patients were found to have electrocardiographic changes that were indicative of myocardial injury. (Three also had elevated levels of creative kinase-MB). Four of five patients with electrocardiographic changes were operated on successfully with the use of perioperative invasive monitoring. None of the 18 patients had congestive heart failure or cardiac dysrhythmias during their hospital course. These data suggest that myocardial damage can result from acute carbon monoxide poisoning, and appropriate screening is indicated for the detection of such injuries. PMID- 1587920 TI - Late onset of extensive brain damage and hypertension in a patient with high voltage electrical burns. AB - An 11-year-old boy sustained high-voltage electrical and flame burns over 85% of his body surface area, 75% of which were full-thickness burns. After 4 months of treatment and multiple operations and skin graftings before his discharge from hospital, he exhibited irritability, hallucinations, and eventually, seizures and respiratory and cardiac arrest. He was resuscitated successfully. Diffuse bilateral brain damage was observed by means of computerized tomography and magnetic resonance imaging. Acute hypertension (up to 290/220 mm Hg) developed the following day. Recovery began 48 hours later. Most clinical symptoms and the hypertension resolved within 1 week. However, the computerized tomographic scans and magnetic resonance imaging findings persisted but were resolved within 2 months. Irritability and low tolerance for frustration were the only remaining symptoms at the time of a 12-month follow-up examination. PMID- 1587921 TI - Burns in alcohol and drug users result in longer treatment times with more complications. AB - Brezel, Kassenbrock, and Stein (J Burn Care Rehabil 1988;9:169-71), surveyed a group of 180 patients who were substance abusers or who were neurologically or mentally impaired and found that their inpatient care was more costly, more complicated, and more lengthy. In our institution we undertook a similar study to determine whether our findings would be similar. During a 12-month period, the charts of all patients over the age of 18 who were admitted for treatment of acute burns were reviewed. One hundred and thirty-one charts were available for study. Review of the charts revealed that 19 (14.5%) met our criterion of being impaired by drugs or alcohol, and the remaining 112 patients served as control subjects. The total body surface area burn averaged 25.8% in the impaired group and 21.3% in the control group. The amount of third-degree burns averaged 11% in the impaired group and 11% in the control group. Although the amount of third degree burns was virtually identical in the two groups, the control group required an average of 1.2 procedures per patient, whereas the impaired group required 2.1 procedures per patient. A list of possible complications or adverse reactions that could occur was used to compare the two groups. The control group averaged 1.83 complications per patient, and the impaired group averaged 3.16 complications per patient. The average length of stay in the hospital for the control group was 19 days, and the average length of stay for the impaired group was 34.1 days.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587922 TI - Epinephrine spray-bottle technique for harvesting skin grafts. AB - Topical epinephrine/saline solution in a concentration of 1:100,000 in a spray bottle can be used to prepare skin graft donor sites for harvesting of split thickness skin. Additional wetting of the dermal bed during harvesting achieves minimal blood loss. The spray application of epinephrine/saline solution is superior to the use of epinephrine/saline compresses placed after harvesting. Skin prewetting and continuous misting during harvesting avoid the establishment of vigorous bleeding in the dermal bed from which the skin is taken and thus lessen total blood loss. PMID- 1587923 TI - Health risks to fire fighters. AB - Fire fighters work in varied and dangerous environments and face unique health hazards that increase their risk for line-of-duty injury and death. While working with sophisticated equipment within such environments, the fire fighter is exposed to high noise levels, changing thermal conditions, and hazardous breathing atmospheres. In addition, his or her protective equipment can impose limitations on efficiency and performance. These conditions have been related to specific physical performance requirements that will reduce line-of-duty injury, disability, and even death. Physical fitness and health maintenance programs that reduce the risk for cardiovascular disease and musculoskeletal injuries have been prescribed for fire fighters. These programs are essential components of any modern fire service. PMID- 1587924 TI - Exercise stress testing for the pediatric patient with burns: a preliminary report. AB - There is no literature concerning postburn exercise tolerance among pediatric patients. In an effort to quantify the endurance capabilities of pediatric burn victims, stress testing of 59 patients was carried out with a modified Bruce protocol. This treadmill test consists of eight 3-minute stages with incremental increases in speed and incline. Fifty-nine patients (37 boys and 22 girls) were tested. The mean burn surface area was 46%; an average of 33% consisted of full thickness burns. The average time since burn injury at which patients were tested was 2.9 +/- 1.9 years. The average age of the patients at the time of test was 11.4 +/- 3.9 years. No differences in exercise tolerance were found among these children irrespective of the presence of inhalation injury, method of excision, or burn size. If these trends continue as more data are accumulated, the long term prognosis for the child with severe burns will be encouraging. PMID- 1587925 TI - Compliance and durability in pressure garments. AB - This study examined the pressure volumetric characteristics (compliance) of Jobst (Jobst Institute, Toledo, Ohio), Barton-Carey (Barton-Carey Co., Perrysburg, Ohio), and Tubigrip (SePro Healthcare Inc., Moorestown, N.J.) pressure garments for arms after repeated saturation with lubricating substances and repeated washing/drying cycles. The three treatment groups were each composed of one sleeve from each of the manufacturers and were subjected to 20 washing/drying cycles. In addition, the sleeves in treatment groups 2 and 3 were saturated with cocoa butter and Lubriderm moisturizer, respectively, before each cycle. Circumferential measurements were taken on the proximal forearm of the sleeve at varying degrees of pressure with a Grafco standard sphygmomanometer (Graham Field Inc., Hauppauge, N.Y.) and a Gulick anthropometric tape measure (Creative Engineering, Plymouth, Mich.). Measurements were taken initially and after every fifth washing/drying cycle. Analysis of variance revealed significant results for the main effects and some interactions at the 0.01 level. Overall results showed little change in the Jobst and Barton-Carey garments, whereas the Tubigrip garments displayed an inconsistent pattern. PMID- 1587926 TI - Research priorities for burn nursing: nursing recruitment, retention, and other administrative issues. AB - This Delphi study was designed to identify nursing research priorities. Ninety four participants completed four rounds of questionnaires that contained 101 potential research questions. Twenty questions addressed nursing administrative issues. In this category, the highest priority for potential impact on patient welfare related to the cost-effectiveness of various infection control measures. Questions concerning recruitment, retention, staffing, and cost/quality issues had the highest priority for research that could have an impact on the profession of nursing. PMID- 1587927 TI - Inaccuracy of nitrogen balance determinations in thermal injury with calculated total urinary nitrogen. AB - Many burn centers use nitrogen balance studies to estimate the adequacy of nutritional support. Nitrogen loss includes the sum of urinary urea nitrogen, nonurea urinary nitrogen, and losses from skin, wound, and stool. Urinary urea nitrogen is often used to calculate total urinary nitrogen by multiplying the urinary urea nitrogen by a factor of 1.25 to account for nonurea urinary nitrogen. This formula is appropriate when applied to a nonstressed individual who has fasted overnight but is not appropriate for patients who have undergone surgery or experienced trauma. We have undertaken this study to assess the predictability of this formula in patients with thermal injuries. Twenty-seven patients with major thermal injuries had random 24-hour urine collections, which were analyzed for both urinary urea nitrogen and total urinary nitrogen. In these patients with burns we found that urinary urea nitrogen represented approximately 65% of the directly measured total urinary nitrogen rather than 80% as assumed by the formula. This increase in the nonurea nitrogen loss is greater than that found after surgery or trauma. Individual measurements may underestimate losses by 20% to 60%. Directly measured total urinary nitrogen should replace calculated total urinary nitrogen as the index of urine nitrogen losses for nitrogen balance studies in patients with burns. PMID- 1587928 TI - Decreasing mortality and morbidity rates after the institution of a statewide burn program. AB - During the late 1970s, a statewide system for burn treatment and prevention was developed in Maine; it was assumed that such a system would reduce mortality and morbidity rates. To examine the effect of this intervention and the validity of its underlying hypothesis, data for the period from 1973 to 1988 were collected from burn unit registries inside and outside of the state and from hospital discharge abstracts, death certificates, and published sources. In Maine, the annual number of deaths per million persons that resulted from fire- and burn related injuries declined from 41 in the years 1973-1980 to 25 in the years 1981 1988, which is a significantly greater decrease than for the United States as a whole (p less than 0.001). This decrease could not be explained by changes in the age or urban and rural distribution of the population. The annual number of hospital admissions for treatment of burns (per million persons) in Maine decreased from 401 to 301 over the same period, and patients with more complicated burns were increasingly referred to more specialized centers within and outside of the state. Since a state system was instituted, hospital mortality rates, when grouped by age and burn area, were not significantly different from those reported by the most prominent burn unit in New England. The population based methods of data collection and linkage that were developed for this investigation may be useful for other studies of injury epidemiology. A statewide burn program appears to have contributed to a reduction in mortality and morbidity rates, primarily through preventive efforts. PMID- 1587929 TI - "The die is cast": telling patients they are going to die. AB - The decision not to resuscitate a patient with burns is an issue of concern, with advocates both for and against. Most patients have not had previous experience with major burn injuries. It is therefore unreasonable to expect them or their families to act from a position of knowledge. There is a subset of patients considered for "do not resuscitate" orders who are nonsurvivors. If the outcome is predictable, the responsibility of the burn team is to inform patients and their families. Such discussion should come within the first few hours of admission, when the patient is fully awake and able to understand, to respond, and to make plans. PMID- 1587930 TI - Computer simulation as a tool for the rapid optimization of the high-performance liquid chromatographic separation of a tryptic digest of human growth hormone. AB - Computer simulation was used to optimize the separation of a tryptic digest of recombinant human growth hormone using reversed-phase high-performance liquid chromatography in a gradient mode. DryLab G/plus software modelled the retention behavior of the complex tryptic digest mixture as a function of gradient conditions, based on data from two experimental gradient runs. The theoretical optimum separation conditions were rapidly obtained and reproduced experimentally. Resolution did not simply increase as gradient steepness was decreased, rather, an intermediate gradient time provided maximum sample resolution. The simulation results also indicate that the method is reasonably rugged, with little change in the separation expected for different high performance liquid chromatography systems, and changes in the separation can be compensated by a change in the gradient steepness. Computer simulation can also be useful to quickly reoptimize conditions for a new column, if it fails to provide the same separation. PMID- 1587931 TI - Benign proliferative disorders of the female tract: a call for a special interest group. PMID- 1587932 TI - Granulosa cells of polycystic ovaries: are they normal or abnormal? AB - Understanding whether granulosa cells are normal or abnormal in women with polycystic ovary syndrome (PCO) could have clinical importance. For this purpose, we compared the ability of normal and PCO granulosa cells to synthesize oestrogen and progesterone in vitro in response to follicle stimulating hormone (FSH) and/or insulin-like growth factor-I (IGF-I). The normal granulosa cells were from a 7 mm dominant follicle from a women with regular menstrual cycles. The PCO granulosa cells were from 5-7 mm follicles of three patients who had classical PCO. Several interesting points emerge from the comparison: in each PCO patient there was a high level of bioactive FSH in the follicular microenvironment (greater than or equal to 5 mIU/ml; greater than or equal to 250 ng/ml). This is paradoxical because the concentration of steroids in follicular fluid suggests that PCO follicles are highly atretic and therefore should not contain detectable FSH activity. The capacity to secrete progesterone when challenged with a maximally effective dose of FSH and/or IGF-I, was markedly reduced (8- to 10 fold) in PCO compared to normal granulosa cells. This is in sharp contrast to the oestradiol responses which were much the same for PCO and normal granulosa cells. Also, the time course and dose-response effects of FSH showed some major differences between normal and PCO cells, that is, PCO cells lost their capacity to produce oestradiol when treated continuously with a maximally effective dose of FSH. They were also significantly more sensitive to FSH and failed to become more sensitive to IGF-I when treated with FSH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587933 TI - Patterns of secretion of human chorionic gonadotrophin by superfused placental explants and the embryo--placental relationship following maternal use of medications. AB - There is great concern regarding maternal exposure to medications, especially in the first trimester of pregnancy because of the possible teratogenic effects. In the present study we have examined the consequences of maternal drug exposure in vivo upon placental secretion patterns of human chorionic gonadotrophin (HCG) and the relationship between the embryo and placenta in vitro. This was examined in samples obtained from various drug-exposed women following elective pregnancy termination at 8-9 weeks. The patterns of HCG secretion in superfused placental explants were different from those seen in control explants (without use of any medication). This was shown by changes in the pulse pattern and pulse frequency. In addition, the exposure of placental explants to various embryonic tissues modified HCG secretion in static cultures. In superfusion, co-perfusion with embryonic spinal cord tissue increased HCG secretion as opposed to that seen in similar incubations made with embryonic spinal cord tissue obtained from healthy women. Thus, our data suggest that maternal drug exposure alters both spontaneous hormone secretion by the placenta and the recently described embryo--placental relationship in vitro. PMID- 1587934 TI - Modification of pulsatile human chorionic gonadotrophin secretion in first trimester placental explants induced by polycyclic aromatic hydrocarbons. AB - The polycyclic aromatic hydrocarbons are major environmental pollutants. Benzo[a]pyrene and 3-methylcholanthrene are prominent members of this group of compounds. In the present study, we have examined the effect of these carcinogens/mutagens upon human chorionic gonadotrophin (HCG) secretion in the first trimester placenta in vitro. At 7-9 weeks in static cultures, exposure to 50 microM benzo[a]pyrene for 24 h increased beta-HCG secretion by placental explants. The effect after 6 h of incubation was less apparent. The effect of 5 microM benzo[a]pyrene at the two time points also was less significant than 50 microM benzo[a]pyrene. In explants exposed to 50 microM 3-methylcholanthrene, the effect on HCG secretion was also stimulatory. In superfusion of placental explants pretreated overnight with benzo[a]pyrene, there was a similar increase in the pattern of pulsatile beta-HCG secretion, as analysed by the area under the curve and the pulse amplitude, which was most evident at 24 h with the 50 microM dose. No significant effect on pulse frequency was noted. The effect of 50 microM 3-methylcholanthrene was also stimulatory. In order to determine the functional integrity of the explants treated with benzo[a]pyrene, the effect of 1 min pulses of 10(-10) gonadotrophin-releasing hormone (GnRH) analogue (a known HCG stimulator in superfusion) was tested, demonstrating that it increased beta-HCG secretion compared to controls. In addition, there was also an increase in whole HCG, as measured by the Tandem-R assay following exposure to benzo[a]pyrene. In conclusion, short-term exposure to carcinogens increases HCG secretion of placental explants in early pregnancy and this effect is maintained after removal of the xenobiotic. PMID- 1587935 TI - Trophoblast tissue culture of human intrauterine and ectopic pregnancies and treatment with methotrexate. AB - The application of drugs for conservative treatment of patients with ectopic pregnancy has been used worldwide for several years. In-vitro studies, however, are very few. We therefore examined the effects of methotrexate on trophoblast tissue cultures derived from intrauterine and ectopic pregnancies. Methotrexate was administered either 12 h or 6 days after initiation of the culture. Human chorionic gonadotrophin (HCG) levels were measured in the culture medium. All cultures showed secretion of HCG within the first 16 days. Methotrexate concentrations less than 3.8 x 10(-4) mol/l had no effect on HCG secretion. Cultures of ectopic pregnancies required a concentration about 10x higher to induce an equivalent reduction of HCG levels compared to intrauterine pregnancies. A few intrauterine and ectopic pregnancies showed no reduction of HCG values after treatment. These results suggest that data obtained from studies on intrauterine pregnancies may not be transferable to ectopic pregnancies in all instances. In some regimens approximately 8 days are required before the effect becomes measurable. In combination with our clinical data, we therefore recommend not to repeat a methotrexate dose too early in treatment of patients with ectopic pregnancies. The possibility that non-responding patients could exist should be kept in mind. PMID- 1587936 TI - Ovarian hyperstimulation syndrome after superovulation using GnRH agonists for IVF and related procedures. AB - Ovarian hyperstimulation syndrome (OHSS) is the most serious iatrogenic complication of ovarian stimulation. In severe cases, haemoconcentration, hypovolaemia, thromboembolism and death may result. It is reassuring that its incidence is not increased after ovarian stimulation for in-vitro fertilization despite very high serum oestradiol levels and large numbers of follicles and oocytes. This may be related to follicular aspiration, expert monitoring or low implantation rates. However, complete prevention has not been achieved despite the wide availability of ultrasound and oestradiol assays, thus presenting the clinician with a continuous challenge. Our aim is to analyse critically the most recent published series of OHSS in in-vitro fertilization and other assisted reproduction techniques using stimulation with gonadotrophin releasing hormone agonists (GnRHa) and human menopausal gonadotrophin (HMG). The main determining factor in the development of OHSS appears to be ovarian predisposition. Patients with polycystic ovarian disease are at a high risk of OHSS and therefore a small dose and slow start of HMG is recommended, tailoring the dosage according to the ovarian response. Accurate prediction by ultrasound and oestradiol assays and strict prevention by withholding human chorionic gonadotrophin (HCG) or cryopreservation of all the embryos have a major impact on the occurrence of OHSS. It is interesting that fixed-schedule IVF cycles, without detailed monitoring, are not associated with an increased incidence of OHSS. The use of GnRHa, despite expectations, is associated with a higher prevalence of OHSS. Luteal phase supplementation with progesterone rather than HCG should be used in cycles where oestradiol is greater than 2500 ng/l or where the number of oocytes exceeded 10.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587937 TI - The effect of luteal support with human chorionic gonadotrophin or progesterone on the daily progesterone profile after different types of ovarian stimulation. AB - Attempts have been made to increase the low pregnancy rate in in-vitro fertilization (IVF) cycles by luteal phase support with progesterone or human chorionic gonadotrophin (HCG). Previously, this practice has been inconsistent and the results unclear. The detailed effect of support on the progesterone profile in the luteal phase was assessed by daily salivary progesterone measurements in non-conception IVF cycles. The comparison of HCG and progesterone support in two different stimulation protocols showed that the profile of luteal progesterone concentrations was similar in control cycles and those supported with a vaginal progesterone suppository, showing an early decrease by the fourth luteal day. In cycles supported with multiple doses of HCG, the progesterone profile was normal but slightly increased up to the 9th luteal day subsequently falling to basal levels by the fourteenth luteal day. PMID- 1587938 TI - Circhoral fluctuations of serum total renin, inhibin and related hormones around the mid-cycle in normal human females. AB - Total renin and inhibin are secreted by the ovary. Although luteinizing hormone (LH) and/or follicle stimulating hormone (FSH) may stimulate their secretion, the close relationship between fluctuations of gonadotrophins, oestradiol, progesterone, renin and inhibin during the cycle is still conjectural. To investigate the temporal relationship between the short-term fluctuations in the circulating concentrations of LH and FSH and the ovarian hormones (oestradiol, progesterone, renin and inhibin), blood samples were collected at 15-min intervals for 6 h from 15 normal women in the late follicular (n = 4), early luteal (n = 5) or luteal (n = 6) phases of the menstrual cycle. LH levels showed the well-known pulsatile secretion with decreasing frequency and increasing relative amplitude from the late follicular to the luteal phase. Progesterone and oestradiol serum levels were pulsatile, 25% and 35-50% of which were linked to LH pulses, with time lags of 30 and 12-15 min respectively. Renin levels presented significant pulses, 26% of which were related to LH pulses with a time lag of less than 10 min; no coincidence was found between renin and oestradiol pulses. Inhibin levels presented only scattered pulses of small amplitude, which were unrelated to LH or FSH. These results show that, besides the LH-related pulses, pulsatile secretion of some ovarian hormones (oestradiol, progesterone and renin) may also occur independently of LH pulses and may be unrelated to one another. Moreover, contrary to the other ovarian hormones, inhibin seems to follow a tonic, not a pulsatile type of secretion around the mid-cycle. PMID- 1587939 TI - The synergistic effects of clomiphene citrate and human menopausal gonadotrophin in the folliculogenesis of stimulated cycles as assessed by the gonadotrophin releasing hormone antagonist Nal-Glu. AB - Clomiphene citrate (CC), alone or in combination with exogenous gonadotrophins, has been widely used in ovulation induction. CC promotes endogenous release of gonadotrophins, yet when used in combination with exogenous gonadotrophins, its contribution to folliculogenesis is difficult to assess. In order to determine the contribution of CC-induced endogenous gonadotrophin production to the overall ovarian stimulation in cycles treated with CC/human menopausal gonadotrophin (HMG), Nal-Glu, a gonadotrophin-releasing hormone (GnRH) antagonist was administered. Fertile women (n = 10) undergoing ovarian stimulation and oocyte aspiration for the sole purpose of gamete donation were studied. Five women received CC (100 mg daily for 5 days) in conjunction with pure follicle stimulating hormone (FSH) 150 IU daily. Five women received HMG alone. Nal-Glu (50 micrograms/kg/day) was administered intramuscularly to both groups when the leading follicles reached a mean diameter of 16 mm. Human chorionic gonadotrophin (HCG) 10,000 IU was given when the largest follicles reached a mean diameter of 20-22 mm. A significant fall in serum oestradiol levels was observed in women given CC/FSH (37.9 +/- 7.3%) within the first 24 h of Nal-Glu administration. Serum luteinizing hormone (LH) decreased greater than 20% within 24 h of Nal-Glu administration and remained low throughout the rest of the treatment. No decrease in oestradiol levels was noted in cycles receiving HMG alone. With supplemental FSH, falling oestradiol levels in CC/FSH cycles rebounded and continued to rise until the day after HCG administration. Despite a drop in oestradiol in CC/FSH cycles, the aspirated oocytes exhibited no untoward effects. The fertilization and cleavage rates were similar, and pregnancies occurred in both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587940 TI - Vaginal disinfection with povidon iodine and the outcome of in-vitro fertilization. AB - In a prospective randomized study, the influence was assessed of vaginal disinfection with a 1% solution of povidon iodine (Betadine), before performing a transvaginal ultrasound-guided oocyte retrieval, on fertilization, cleavage rate and pregnancy rate. The outcome of 334 oocyte retrievals was studied. In 160 cases, Betadine was used and in the remaining 174 cases, normal saline was used. No differences in the fertilization and cleavage rates were found (fertilization 45.5% versus 47.8%, cleavage 49.8% versus 52.1% in the Betadine and normal saline groups respectively). However the pregnancy rate was significantly higher in the normal saline group (17.2% versus 30.3% clinical pregnancies per embryo transfer). No increase in infection risk occurred in the saline group. PMID- 1587941 TI - Intrauterine insemination: critical analysis of a therapeutic procedure. AB - Donor intrauterine insemination with washed spermatozoa (fresh semen) was performed in 36 women (63 cycles) whose husbands had azoospermia due to primary or secondary testicular failure. Simultaneously a control group of 76 couples (156 cycles) with proven fertility, who had recently discontinued mechanical non hormonal contraception, were encouraged to have sexual intercourse during the fertile period. The age of the women was similar in both groups and the timing criteria were also similar. The pregnancy rate per woman was 50% in the donor insemination group and 47.4% in the control group (difference not significant). The pregnancy rate per cycle was 28.6% in the artificial insemination group and 23.1% in the control, natural insemination group (difference not significant). The number of artificial or natural insemination cycles required to achieve pregnancy was similar in the study and control groups. This study suggests that when the inseminating spermatozoa and female partner are normal, as occurs in the donor insemination group, intrauterine insemination is as efficient as natural insemination in achieving pregnancy but is not more successful. PMID- 1587942 TI - Comparison of attitudes of donors and recipients to oocyte donation. AB - The attitudes of volunteer donors and recipients undergoing treatment in an ovum donation programme were studied in order to assess both the psychological and psycho-social aspects of the procedure. A questionnaire was sent to 35 donors and 60 recipients. All donations were unpaid. Fifty-eight were anonymous donations and three were known. Eighty-six per cent of recipients and 74% of donors had told at least one person other than their partner. Eighty per cent of donors and 66% of recipients agreed that donors should not be paid. Sixty-three per cent of donors would donate if the recipient was told their name but only 26% of recipients would accept if the donor was given their name. Seventy per cent of the donors would donate to someone they knew but would rather donate anonymously. Ninety per cent of recipients were strongly against the donor contacting the child later in life but 54% of donors had no objection to the child contacting them. Eighty-six per cent of recipients and 56% of donors felt that if they had been born from a donated oocyte, they would not want to know. PMID- 1587943 TI - Cigarette smoking and outcomes of in-vitro fertilization and embryo transfer: a prospective cohort study. AB - A prospective cohort study of 222 consecutive couples undergoing 297 cycles of in vitro fertilization and embryo transfer (IVF-ET) was conducted to evaluate the impact of cigarette smoking in males and females. Compared with non-smokers, females smoking at the time of treatment had more previous pregnancies (1.16 versus 0.63, P less than 0.001), consumed more coffee per day (3.29 versus 1.85 cups, P = 0.001) and were less likely to hold a professional or skilled job (41% versus 66%). There was no difference in the response to ovarian stimulation in terms of the duration and dose of human menopausal gonadotrophin, peak oestradiol level or number of oocytes retrieved. The fertilization rate was actually higher in heavy smokers than in non-smokers (79.3% versus 61.3%, P = 0.007). The rate of embryo cleavage was retarded in a dose-dependent fashion. In smokers of 1-14 cigarettes/day, the likelihood of transferring an embryo at greater than or equal to 4-cell stage was 0.87 [95% confidence limits (CL) 0.56-1.4] and in smokers of greater than or equal to 15 cigarettes/day, the likelihood was 0.52 (95% CL 0.31 0.88). However, evaluation of interrelated factors using logistic regression suggested that a low socioeconomic status had a greater detrimental effect on embryo cleavage rate than female smoking. No significant difference was noted in the clinical outcome following embryo transfer. A study of larger sample size is required to evaluate whether the effects of cigarette smoking are independent of socioeconomic status and other related factors and whether they result in reduced ongoing clinical pregnancy and live birth rates. PMID- 1587944 TI - World collaborative report on IVF-ET and GIFT: 1989 results. PMID- 1587945 TI - Subclavian vein thrombosis: a late complication of ovarian hyperstimulation syndrome. AB - Two cases of subclavian vein thrombosis following ovarian stimulation for in vitro fertilization and subsequent ovarian hyperstimulation syndrome (OHSS) are described. Both occurred several weeks after complete resolution of the OHSS. The site of the lesions and their timing suggest that there is a generalized disturbance of coagulation associated with OHSS, which persists beyond the duration of the clinical syndrome. PMID- 1587946 TI - Couples with exclusively female offspring have an increased probability of a male child after using male sex preselection. AB - The present study was undertaken to determine whether couples with one or more daughters and no sons had an increased probability of having a male child after using male sex preselection. The sex ratio of children born to couples after using 'protocol 3' (n = 70) or 'modified protocol 3' (n = 28) male sex preselection at one of 14 centres was determined. The normal approximation to the binomial distribution was used to determine significant differences between these sex ratios and the established sex ratio for children born to couples with one previous daughter and no sons. The sex ratios of both protocol 3 sex-preselected children (73.0%; P less than 0.0001) and modified protocol 3 sex-preselected children (86%; P less than 0.0001) were significantly different to the established sex ratio (control) for a current child born to parents with one previous daughter and no sons (50.1%). Couples with one or more daughters and no sons will have an increased probability of a male child after using male sex preselection. PMID- 1587947 TI - Effects of 1,2-propanediol on the cytoskeletal organization of the mouse oocyte. AB - The effects of 1,2-propanediol, a cryoprotectant used for the freezing of embryos, were tested on the organization of microtubules and microfilaments in mouse oocytes arrested in metaphase II. At low doses (less than or equal to 1.0 M), 1,2-propanediol induced disorganization of the meiotic spindle but at 1.5 M and higher, it stabilized the spindle. Cytoplasmic asters were observed at all doses tested. An extensive network of free microtubules was observed at 1.0 M and 2.0 M 1,2-propanediol, the former having the stronger disruptive effect on the spindle. Higher doses of 1,2-propanediol (greater than or equal to 1.5 M) caused the oocytes to form cytoplasmic blebs. These blebs lacked detectable cortical microfilaments. In contrast, the microfilament-rich area of the cell cortex overlying the meiotic spindle was not modified. PMID- 1587948 TI - Oocyte dysmorphism and aneuploidy in meiotically mature human oocytes after ovarian stimulation. AB - The frequency of aneuploidy in 583 newly aspirated, uninseminated metaphase II stage human oocytes which exhibited seven distinct forms of cytoplasmic dysmorphism [Van Blerkom (1990) J. Electron Microsc. Tech., 16,324] after ovarian stimulation and ovulation induction was determined in the living state by DNA fluorescence followed by fixation and air-drying for karyotyping. The findings demonstrate that as many as half of the oocytes with dysmorphic phenotypes which arise early in meiotic maturation are aneuploid, with hypohaplidy predominant. In contrast, cytoplasmic defects which occur at or after metaphase I are associated with a relatively low frequency of aneuploidy (less than 15%), which is comparable to that previously reported for human oocytes with a normal cytoplasmic appearance [Van Blerkom and Henry (1988) Hum. Reprod., 3, 777]. The aetiologies of aneuploidy in dysmorphic oocytes, as well as the clinical implications for oocyte selection in laboratory-assisted conception are discussed. PMID- 1587949 TI - Temporal effects of taurine on mouse preimplantation development in vitro. AB - Previously it has been shown that significantly more 2-cell mouse embryos reach the blastocyst stage when cultured in medium supplemented with taurine. In this study, in-vitro fertilized zygotes from a hybrid mouse strain were used to examine the temporal effects of 10 mM taurine on embryonic development in vitro during the preimplantation period. Taurine exerted its beneficial effect exclusively during the first 2 days post-insemination. The effect of taurine on blastocyst formation appeared to be restricted mostly to the period 20-48 h after fertilization, during which time mouse embryos are at the two-cell stage. Although more blastocysts were found when embryos were cultured in taurine containing medium from 5 to 20 h post-insemination, this difference was not significant compared to the number of blastocysts when embryos were cultured without taurine. Taurine did not appear to affect the two-cell block of mouse embryos from random-bred strains. PMID- 1587950 TI - Use of fetal bovine serum to protect against zona hardening during preparation of mouse oocytes for cryopreservation. AB - Addition of 20% fetal bovine serum (FBS) to media used for cryopreservation does not reduce the premature release of cortical granules but does prevent their action on the zona pellucida and thereby prevents zona hardening. In this paper, it is shown that the washing period required for removal of FBS is less than 12 min for cumulus-free oocytes and between 150 and 170 min for cumulus-intact oocytes. When these washing periods are observed after exposure of oocytes to the cryoprotectant dimethylsulphoxide (DMSO; 1.5 M) in the presence of 20% FBS, a subsequent exposure to calcium ionophore A23187 or a second exposure to 1.5 M DMSO both lead to zona hardening. This result suggests that sufficient cortical granules remain to elicit a block to polyspermy at fertilization. Oocytes, which had been exposed to DMSO and FBS and then washed free of both, were fertilized in vitro; the incidence of polyspermy was not found to be elevated over the level found in controls. PMID- 1587951 TI - Immunohistochemical expression of endometrial proteins and pregnancy outcome in frozen embryo replacement cycles. AB - The expression of two endometrial proteins, pregnancy-associated endometrial alpha-2 globulin (alpha-2 PEG) and 24K protein, was examined immunohistochemically in an attempt to identify a marker or a pattern which would predict subsequent implantation. Patients who had undergone in-vitro fertilization cycles and had at least three frozen embryos were recruited into the study. They received two cycles of hormone replacement therapy. The first was a monitored cycle in which dated endometrial biopsies were taken for immunohistochemical assessment using monoclonal antibodies to alpha-2 PEG and 24K protein and also for standard histological dating. In the second cycle, the frozen-thawed embryos were replaced. The results of the monitored cycle were then correlated with the pregnancy outcome in the transfer cycle. Ten patients conceived, of whom eight had a pattern of low immunohistochemical staining of alpha-2 PEG and high immunohistochemical staining of 24K. In the 15 patients who did not conceive, four had the same endometrial protein pattern (P less than 0.05). In the 13 specimens classified as histologically in phase, 10 (71%) showed incompatible protein expression. We conclude that the pattern of expression of the endometrial proteins alpha-2 PEG and 24 K may be potentially useful to indicate a receptive endometrium. Immunohistochemistry may yield information on endometrial development which is not apparent from routine histological assessment. PMID- 1587952 TI - Endometrial pattern and thickness associated with pregnancy outcome after assisted reproduction technologies. AB - The endometrial pattern and thickness was analysed prospectively on the day of administration of human chorionic gonadotrophin (HCG) in 200 in-vitro fertilization (IVF), gamete intra-Fallopian transfer (GIFT) and tubal embryo transfer (TET) cycles. Increasing maturity of the endometrial pattern was positively correlated with oestradiol levels (r = 0.20; P = 0.005), number of mature eggs (r = 0.13; P less than 0.05) and the number of top quality embryos (r = 0.40; P less than 0.001). The endometrial thickness was positively correlated with the number of follicles greater than or equal to 15 mm (r = 0.15; P less than 0.02) and the cycle day on which HCG was administered (r = 0.14; P less than 0.03). It was unaffected by the dose of human menopausal gonadotrophin and was negatively correlated with the use of clomiphene citrate (r = 0.40; P less than 0.001). Fecundity was increased for IVF when the endometrial thickness was greater than or equal to 9 mm (P less than 0.05) and for GIFT and TET when a Type C triple-line endometrial pattern was present (P less than 0.05). Biochemical pregnancies for the combined methods increased from 2.5% of all pregnancies when the endometrial thickness was 9-13 mm, to 27.8% when the thickness was less than 9 mm or greater than 13 mm (P less than 0.01). Biochemical pregnancies occurred in 67% of IVF pregnancies when the endometrial thickness was greater than or equal to 3 mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587953 TI - Preterm delivery, low birthweight and small-for-gestational-age in liveborn singleton babies resulting from in-vitro fertilization. AB - The Medical Research Council In-Vitro Fertilization (IVF) Register report on births resulting from assisted conception in Great Britain demonstrated a high incidence of preterm and low birthweight babies. This incidence remained high even when the analysis was restricted to singleton babies. The present paper investigates possible risk factors for prematurity, low birthweight and small-for gestational-age (SGA) in singleton IVF births. Thirteen per cent of singleton IVF babies were preterm, 11% low birthweight and 17% small-for-gestational-age. Analysis by multiple regression indicated that hypertension during pregnancy was an independent risk for preterm delivery, low birthweight and SGA, bleeding during pregnancy for preterm delivery, and the number of embryos transferred and the type of infertility for low birthweight. PMID- 1587954 TI - Hydatidiform mole coexisting with a fetus in twin gestation following gonadotrophin induction of ovulation. AB - A case is presented of a twin gestation comprising a grossly normal fetus and placenta coexisting with a separate hydatidiform mole which ended in an abortion. Both developed following ovulation induction with human menopausal gonadotrophin and human chorionic gonadotrophin. The literature is reviewed and clinical aspects of this rare entity are discussed. PMID- 1587955 TI - Pharmacotherapy of unstable angina. AB - All patients with unstable angina should be admitted to a coronary or an intensive care unit. There should be an attempt to classify the patient according to the proposed Braunwald nomenclature. If the patient has a secondary cause for unstable angina (e.g., tachyarrhythmia, heart failure, fever, thyrotoxicosis, severe hypertension, hypoxia, unusual emotional stress, or anemia), this condition should be treated initially with therapy specific for that etiology. If the patient does not have a secondary etiology, therapy should be initiated with nitrates, preferably intravenous nitroglycerin. Heparin should be concomitantly administered. If the patient cannot receive heparin, aspirin should be initiated. All patients should receive beta-blockers. If the patient cannot take a beta blocker, a calcium antagonist (probably diltiazem) should be initiated. However, if the patient is refractory to beta-blockers, the dihydropyridine nifedipine should be added. Failure to all pharmacologic interventions necessitates a progressive invasive approach dictated by the potential surgical risk of the patient. Long-term aspirin and beta-blockers should be strongly considered. PMID- 1587956 TI - Clinical pharmacology training at the Food & Drug Administration. AB - Challenged with the clearly demonstrated need for highly trained clinical pharmacologists for new drug development and review activities, the FDA Center for Drug Evaluation and Research (CDER) established an internal Staff College. This organizationally unique and innovative unit addressed the educational needs of both the new and the veteran CDER scientists. A multileveled strategy was conceptualized and implemented as described. PMID- 1587957 TI - Antimicrobial activity and pharmacology. PMID- 1587958 TI - Moricizine pharmacokinetics in renal insufficiency: reevaluation of elimination half-life. PMID- 1587959 TI - Effects of combined bezafibrate-simvastatin appraised in healthy subjects. AB - The occurrence of clinical and biochemical side effects of bezafibrate (400 mg daily) or simvastatin (20 mg daily) alone or combined was appraised in 13 healthy male normolipidemic subjects according to a single blind design. Each period of 2 weeks of treatment with bezafibrate or simvastatin or bezafibrate plus simvastatin was followed by a period of placebo (1 week). No subjects experienced myalgia or muscle weakness. Plasma creatine kinase (CK) elevations, particularly skeletal muscle CK (CK-MM), were observed in 6 subjects: 11 times during different placebo periods, 5 times on bezafibrate, 4 times on simvastatin, and 4 times on combined bezafibrate-simvastatin, but never reached 1,600 IU/L. Only a trend to an increase of CK mean values on combined bezafibrate-simvastatin was shown. The hepatic transaminase and gamma-glutamyltransferase activities remained unmodified throughout the trial, unlike alkaline phosphatase activity, which fell on bezafibrate and on bezafibrate plus simvastatin. The low-density lipoprotein cholesterol level was more reduced with simvastatin than with bezafibrate. The addition of bezafibrate to simvastatin did not decrease it further. Lecithin:cholesterol acyltransferase activity expressed as fractional esterification rate was enhanced only on simvastatin and bezafibrate-simvastatin. PMID- 1587960 TI - Pharmacokinetic comparison of a slow-release clonidine with a conventional formulation after acute and chronic administration in hypertensives. AB - The pharmacokinetic characteristics of a slow-release formulation of clonidine (150 micrograms) were compared with those of a conventional formulation (75 micrograms) after acute and chronic (2 week) administration to 12 hypertensive subjects. The Tmax of the slow-release formulation was significantly later than for the conventional formulation after both acute (8.3 +/- 6 hr vs. 2.1 +/- 2 hr) and chronic administration (4.0 +/- 3 hr vs. 2.5 +/- 2 hr). Although the Tmax did not change significantly with acute and chronic administration of the conventional preparation, it was significantly shorter after chronic administration of the slow-release formulation when acute and chronic administration were compared. The Cmax was approximately 60% lower for the slow release formulation (1 x 150 micrograms; 0.42 +/- 0.09 ng/mL) compared with the conventional formulation (2 x 75 micrograms; 0.70 +/- 0.12 ng/mL) after acute administration, whereas in the steady state, in which the dose of the conventional preparation was halved (75 micrograms), the Cmax values were comparable: 1 x 150 micrograms-0.99 +/- 0.27 ng/mL, 1 x 75 micrograms-0.84 +/- 0.20 ng/mL and the dose-normalized interdose AUC were identical for the conventional (16.2 +/- 4.3 ng/mL.hr) and slow release (16.6 +/- 5.3 ng/mL.hr) products. T1/2 values for the conventional formulation of clonidine exceeded 20 hours in all but one subject and were considerably longer than those in previous reports, including those of the authors, in which a less sensitive assay was used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587961 TI - Effect of age and dose on the incidence of adverse events in the treatment of hypertension in patients receiving terazosin. AB - Selected adverse events were evaluated from the combined randomized placebo controlled clinical trials (once-a-day or twice-a-day; monotherapy or combination therapy) of terazosin in hypertensive patients. The designs of these clinical trials were either titration to response or titration to a fixed dose. A grouped survival methodology using logistic regression, developed by Hosmane et al, was used to study the effects of age and dose on the incidence of adverse events. The analysis indicated that except for palpitations, nausea, headache, and dizziness the incidence of adverse events was not significantly related to either age or dose. Palpitations and headache decreased with increasing age and increasing dose and age, respectively. Dizziness and nausea increased at the maximum dose of 20 mg, but not at the 5- or 10-mg doses. PMID- 1587962 TI - Transdermal clonidine as an adjunct to enalapril: an evaluation of efficacy and patient compliance. AB - This four-center, 20-week, open-label study evaluated transdermal clonidine as an adjunct to enalapril 10 mg daily and demonstrated patterns of compliance. Seventy four mildly to moderately hypertensive patients (mean seated blood pressure, 150/101 mm Hg) received enalapril 10 mg once daily as initial monotherapy. In 66 patients, the seated diastolic blood pressure remained greater than or equal to 90 mm Hg at the trough blood levels of enalapril. Transdermal clonidine (3.5 cm2, 7.0 cm2, or 10.5 cm2, equivalent to 0.1 mg, 0.2 mg, and 0.3 mg clonidine/day, respectively) then was added as needed to achieve blood pressure control. Forty eight patients achieved diastolic blood pressures less than 90 mm Hg on concomitant therapy; 44 patients completed 8 weeks of maintenance dosing with a mean blood pressure of 134/85 mm Hg. Oral compliance, as measured by an electronic device that was actuated each time the medication vial was opened, varied from 48 to 140%. Compliance with the transdermal clonidine regimen was excellent; the patch was worn as directed during 96% of the patient-weeks of therapy. The authors conclude that blood pressure can be controlled by a combination of transdermal clonidine and enalapril in patients that do not adequately respond to enalapril monotherapy. Patients poorly complying with oral regimens may be candidates for a trial of transdermal clonidine monotherapy. PMID- 1587963 TI - Increases in methyldopa absorption and renal excretion after multiple doses. AB - A retrospective analysis of previous studies examining methyldopa absorption suggested the possibility that the absorption of methyldopa might increase on repeat methyldopa ingestion. A prospective study was undertaken to determine the effect of repeated oral doses of methyldopa on methyldopa absorption. Thirteen healthy subjects ingested single 250 mg methyldopa doses on days 0, 7, 14, 28, 56, and 112; 24 urine samples were collected and analyzed for methyldopa and its major metabolites on each study day and methyldopa plasma levels were measured over 8 hours at days 0 and 56. There were significant increases in the absorption of methyldopa (as estimated by the urinary excretion of methyldopa and the measured metabolites over 24 hours) at day 56 (33.4 +/- 8.9%, P less than .025) compared with day 0 (26.0 +/- 10.8%). There was also a significant increase in renal clearance of unmetabolized methyldopa (62.7 +/- 13.6 vs. 99.3 +/- 29.1 mL/min, P less than .01) and a decrease in the plasma half-life of methyldopa at day 56 (2.22 +/- 0.91 vs. 1.56 +/- 0.68 hr, P less than .05). There was a tendency toward increases in methyldopa absorption at day 7, 14, 28, and 112. Several possible explanations for the changes in methyldopa disposition are discussed. PMID- 1587964 TI - Sustained-release verapamil formulations for treating hypertension. AB - Verapamil, the first calcium-channel blocker to be introduced for clinical use, is a major drug used for the treatment of systemic hypertension. During the past 10 years, the use of verapamil for hypertension has produced a considerable clinical database to support the efficacy and safety of the agent in many patients. Because of its short half-life, verapamil was originally administered 3 to 4 times daily. During the past decade, a sustained-release formulation of verapamil has been marketed in the US. This product allows for once-daily dosing up to 240 mg/d; however, when higher doses are needed, this sustained-release formulation should be administered twice daily. In addition, the medicine should be taken with food to avoid the high peak blood levels of verapamil, which appears to be related to the delivery system. A new pellet-filled capsule formulation of verapamil (Verelan, Lederle, Wayne, NJ and Wyeth-Ayerst, Philadelphia, PA) is available and provides controlled absorption, 24-hour blood pressure control, improved peak-to-trough plasma levels, and once-daily dosing regardless of dosage size. Prolonged-release verapamil can be taken without food. PMID- 1587965 TI - Inhaled corticosteroids in asthma: a dose-proportionality study with triamcinolone acetonide aerosol. AB - The systemic exposure to triamcinolone acetonide (TAA) after inhalation of aerosolized drug has not been examined previously. This study evaluates the plasma concentrations, pharmacokinetics and dose proportionality of TAA after single oral inhalations at doses of 400, 800, and 1600 mcg. Nine moderately asthmatic male patients received each of the doses in a randomized crossover manner using a 1-week washout period between dosing. Serial blood samples were collected for 10 hours postdosing for the determination of plasma TAA concentrations by using a specific radioimmunoassay. The pharmacokinetic profiles that were obtained showed slow and limited absorption over the first 4 hours after dosing followed by rapid elimination with a half-life of approximately 2 hours (range: 1.8-2.3 hr). Comparison of pharmacokinetic parameters from each dose group showed excellent proportionality and consistent absorption for all patients. Mean Cmax values ranged from 0.51 ng/mL after the 400 mcg dose to 1.01 ng/mL and 1.97 ng/mL after the 800 and 1600 mcg doses, respectively. Mean AUC0-10 values for these same doses were 2.6 ng x hr/mL, 5.3 ng x hr/mL and 10.5 ng x hr/mL, respectively. The results suggest that systemic exposure to TAA is minimal after oral inhalation, occurs in a dose proportional fashion, and produces circulating plasma concentrations which are unlikely to have significant adverse systemic effects. PMID- 1587966 TI - No influence of single intravenous doses of omeprazole on theophylline elimination kinetics. AB - The influence of single intravenous doses of omeprazole on the pharmacokinetics of intravenously administered theophylline was studied in eight healthy male volunteers. In a partially randomized three-period crossover design, an IV infusion of theophylline (400 mg over 30 min) was combined with IV omeprazole (either 40 mg over 2.5 min or 80 mg over 5 min) or with IV placebo (over 2.5 min). Theophylline and omeprazole plasma concentrations were measured over 24 hours after the start of the infusions and pharmacokinetic parameters were calculated. The theophylline plasma concentration-time profiles after omeprazole coadministration were virtually identical to the corresponding profile after placebo administration. For each of the pharmacokinetic parameters of theophylline, the 90% confidence intervals of the omeprazole coadministrations were within the 80 to 120% bioequivalence range with respect to the placebo coadministration. Omeprazole plasma concentrations indicated a biexponential decline in most subjects, with a more rapid elimination after the 40-mg than after the 80-mg dose (P less than .01). Doubling the dose caused an almost three fold increase of AUC resulting in a difference in clearance (P less than .02), whereas the volume of distribution was similar. The results of this study indicate that the metabolism of theophylline is not affected by single intravenous doses of omeprazole. The nonlinear pharmacokinetics of omeprazole are ascribed to saturation of its main metabolizing enzyme, S-mephenytoin hydroxylase. PMID- 1587968 TI - Research, education, caries, and care--taming and turning the restorative tiger. PMID- 1587967 TI - Comparative investigation of the influence of nizatidine, ranitidine, and cimetidine on the steady-state pharmacokinetics of theophylline in COPD patients. AB - The influence of usual regimens of the H2 blocking drugs, cimetidine, ranitidine, and nizatidine on the steady-state plasma concentrations and pharmacokinetic characteristics of theophylline was studied in seventeen patients with chronic obstructive pulmonary disease (COPD). Patients were dosed to steady-state with an oral, sustained-release formulation of theophylline given in therapeutic doses twice daily for 2 weeks. Over the next 4 weeks, each patient received a week-long regimen of each H2 blocker concomitantly with theophylline, and a week-long regimen of theophylline alone (control). At the end of each of the latter 4 weeks the steady-state pharmacokinetics of theophylline were assessed. Neither ranitidine nor nizatidine treatment altered the steady-state pharmacokinetics of theophylline relative to the control phase (i.e. no H2 blocker treatment). Values for theophylline C(ave), Cssmax, AUC0-12, and CLoral were significantly different during cimetidine treatment compared with all other treatments (ranitidine, nizatidine, and control). Cimetidine increased theophylline Cssmax, AUC0-12 and Cave by approximately 32%, and decreased theophylline oral clearance by approximately 23%. The authors conclude that cimetidine alters the steady-state pharmacokinetics of theophylline in COPD patients, whereas ranitidine and nizatidine are without effect. PMID- 1587969 TI - Divisional abstracts. PMID- 1587970 TI - Assessment of cognitive, psychiatric, and behavioral disturbances in patients with dementia: the Neurobehavioral Rating Scale. AB - OBJECTIVE: To assess the validity of the Neurobehavioral Rating Scale (NRS) in patients with Alzheimer's disease (AD) or multi-infarct dementia (MID) and to characterize the cognitive, psychiatric, and behavioral disturbances that occur in these patients. DESIGN: Cross-sectional evaluation. SETTING: West Los Angeles VAMC Geropsychiatry Inpatient Unit, Neurobehavior Inpatient Unit, and Dementia Clinic; UCLA Alzheimer's Disease Clinic. PATIENTS: Convenience sample of 61 patients with AD and 22 patients with MID. MAIN OUTCOME MEASURE: The NRS, a 27 item observer-rated instrument that measures cognitive, psychiatric, and behavioral disturbances. RESULTS: The NRS demonstrated content and convergent validity in this patient group. Principal components analysis of the NRS ratings identified a six-factor solution, and each factor contained clinically related symptoms. The factors were Cognition/Insight, Agitation/Disinhibition, Behavioral Retardation, Anxiety/Depression, Verbal Output Disturbance, and Psychosis. Among the patients with AD, agitation, disinhibition, hostility, poor insight, poor motivation, suspiciousness, and delusions were more severe in patients with more advanced dementia. Depressive symptoms occurred with equal severity in patients with mild and advanced dementia, but depressed mood was more severe in patients with earlier age of onset of AD. CONCLUSION: The NRS is a useful instrument for structured assessment of a broad range of cognitive, psychiatric, and behavioral disturbances in patients with dementia. PMID- 1587971 TI - Role of the opioid system in the hypodipsia associated with aging. AB - OBJECTIVE: To compare the effects of the opioid antagonist, naloxone, on fluid ingestion in young and older males, in order to estimate the role of the opioid system in hypodipsia of older men. DESIGN: Single-blinded, randomized, cross over, placebo-controlled study. SETTING: Outpatient Department of Veterans Affairs. STUDY PARTICIPANTS: Sixteen young subjects (aged 23 to 39) and eight older subjects (aged 69 to 75). All subjects were healthy, community-dwelling, non-smoking men, on no medications. INTERVENTION: Subjects were randomized to receive either placebo or naloxone on day one. Whichever substance the subject did not receive was given on day two with days one and two separated by at least a 2-week washout period. MAIN OUTCOME MEASURES: Fluid intake after overnight food and fluid deprivation, with placebo or naloxone injected in the morning. RESULTS: After overnight fluid deprivation, older individuals consumed 29% less fluid in 2 hours compared with younger individuals (ns). After overnight fluid deprivation and injection with naloxone 100 micrograms/kg, fluid intake was diminished by 42% (P less than 0.05) in young subjects compared with placebo, but only by 7% (ns) in older subjects. Subjective ratings did not differ significantly between young and old subjects. CONCLUSIONS: These preliminary data suggest that the opioid system plays a role in the drinking response in young subjects while failing to alter fluid intake in older subjects. Hypodipsia in older individuals may be due to a deficit in the opioid drinking drive. PMID- 1587972 TI - The effect of age on driving skills. AB - OBJECTIVE: To assess the effect of age on driving skills independent of the limitations related to disease or dementia. DESIGN: Prospective comparison of driving skills across three age groups. SETTING: A university-based research study of student and university-affiliated volunteers. PARTICIPANTS: Healthy elderly (age 65+), teen-age (age 18-19), and young adult drivers (age 25-35). Twenty subjects in each age group were recruited after meeting entry criteria for the study. MAIN OUTCOME MEASURES: Total error count and score on the Miller Road Test, a standardized road test developed by the Division of Bus and Traffic Safety in North Carolina. RESULTS: The elderly were found to have fewer errors than either of the two younger groups of drivers (P = 0.0013). Specific driving skills were judged to be either superior or unchanged in the elderly subjects in comparison to their younger counterparts. CONCLUSIONS: Road test skills appear to be well preserved in the healthy elderly population. More road test studies are needed on elderly individuals with mental and physical impairments to determine if road tests can play a role in identifying the driver at high risk for a crash. PMID- 1587973 TI - The use of goal attainment scaling in a geriatric care setting. AB - OBJECTIVE: Goal attainment scaling (GAS) is a measurement approach used extensively in mental health. It accommodates multiple individual patient goals, yet retains mathematical properties allowing comparisons between patients. This study was carried out to investigate the feasibility and measurement properties of GAS in a geriatric care setting. DESIGN: Prospective descriptive study. SETTING: The geriatric restorative care service and geriatric assessment unit at Camp Hill Hospital, a 350-bed tertiary care facility in Halifax, Canada. PATIENTS: Fifteen patients aged 65 to 94 who were consecutively admitted to the two geriatric services (mean age 79 years, mean length of stay 37 days, 9 females). INTERVENTION: Goal Attainment follow-up guides were developed independently for each patient by two geriatricians after a comprehensive assessment of the patient. These guides were later compared to assess level of agreement in goal setting and scale development. A single goal attainment follow up guide was then developed for each patient by consensus of the two geriatricians. At the end of the follow-up, the guides were scored independently for each patient by one of the geriatricians and by the patient's primary care nurse. MAIN OUTCOME MEASURES: GAS scores were determined on admission and discharge. Each patient also received admission and discharge ratings on the Barthel Index as well as a global rating of outcome (on a subjective 10-point scale) by a geriatrician who was blinded to the Goal Attainment follow-up score. RESULTS: GAS proved feasible, requiring 15-20 minutes to scale an average of six goals per patient. GAS also appears reliable. Of 87 goals, 71 (82%) were identified independently by two geriatricians, and the remainder were determined by consensus. This is also a measure of content validity. The physician-nurse inter-rater reliability was 0.87 (intraclass correlation). Concurrent validity was assessed by correlation with the Barthel Index (r = 0.86) and the global clinical outcome rating (r = 0.82). Content validity was also assessed by comparing our goal areas with those identified in recent consensus reports on geriatric assessment. Of these 13 assessment areas, 12 appeared to be reasonably well covered while one assessment area (sexual problems) was not identified for any of the 15 patients. CONCLUSIONS: GAS appears to be a feasible method of goal setting and outcome evaluation in geriatric care settings, with promising reliability and validity. PMID- 1587974 TI - The Clock Test: a sensitive measure to differentiate normal elderly from those with Alzheimer disease. AB - OBJECTIVE: To examine the clinical utility of the Clock Test for identifying dementia. DESIGN: Group comparisons. SETTING: A hospital-based out-patient diagnostic clinic. PATIENTS: Volunteer sample of elderly individuals (normal elderly, NE, n = 62) and a referred sample of probable Alzheimer Disease (AD, n = 58) patients meeting NINCDS-ADRDA criteria. MAIN OUTCOME MEASURE: The Clock Test is composed of three components: Clock Drawing, Clock Setting, and Clock Reading. A detailed scoring system for qualitative as well as quantitative evaluation of Clock Drawing errors was used. Five time settings, varying in level of complexity, were used to evaluate Clock Setting and Clock Reading. RESULTS: The groups differed significantly on Clock Drawing, Clock Setting, and Clock Reading (P less than 0.001). On Clock Drawing, the AD group made significantly more errors of omission and misplacement of numbers than the NE group (P less than 0.001). Using cut-off scores derived to maximize separation between the groups to define deficits in performance, the sensitivity and specificity for the diagnosis of AD of Clock Drawing, Clock Setting, and Clock Reading were 92% and 86%, 87% and 97%, 92% and 85%, respectively. Using a criterion of deficits on two or more of the three components, sensitivity and specificity increased to 94% and 93%, respectively. CONCLUSIONS: Deficits on clock drawing in AD may be reflective of a generalized disturbance in the conceptualization of time rather than constructional apraxia, per se. The functionally relevant components of Clock Setting and Clock Reading combined with Clock Drawing make the Clock Test particularly useful as a screening and research tool for AD. PMID- 1587975 TI - Comparing proxy and patients' perceptions of patients' functional status: results from an outpatient geriatric clinic. AB - OBJECTIVE: To compare ratings of patients referred for geriatric evaluation and their proxies with respect to patients' ability to perform activities of daily living. DESIGN: Retrospective chart audit. SETTING: University-based Outpatient Geriatric Clinic. PATIENTS: Elderly medicine patients referred to a university based outpatient geriatrics clinic for the first time. MAIN OUTCOME MEASURES: Modified Katz Physical Activities of Daily Living (PADL) and Instrumental Activities of Daily Living (IADL). RESULTS: With regard to PADLs, patients were generally rated as independent by both patients (91%) and proxies (87%); for IADLs, ratings of independence by both patients (68%) and proxies (51%) were significantly lower. Concordance between patient and proxy ratings was significantly (P less than 0.001) greater for PADLs (92%) than for IADLs (82%). When disagreement occurred, patients consistently rated themselves as more independent than their proxies, especially for IADLs. Moreover, concordance between patients and proxies regarding IADLs was significantly (P less than 0.001) worse for patients who had scores below 24 on the Folstein Mini-Mental State Examination (72%) compared with those scoring 24 or higher (95%). CONCLUSIONS: Patient and proxy ratings were concordant when rating patients' ability to perform PADLs. Moreover, concordance was extremely high on IADLs when patients' Folstein scores were 24 or higher. Concordance with respect to IADLs was relatively poor only among patients with Folstein scores below 24. In that case, patients had a more optimistic view of their independence, compared with their proxies. PMID- 1587976 TI - An outbreak of influenza A (H3N2) in a well immunized nursing home population. AB - OBJECTIVE: To describe the epidemiologic features of an outbreak of influenza A that occurred in a skilled nursing home although over 90 percent of the resident population had previously received influenza vaccine. DESIGN: Retrospective cohort study. SETTING: Skilled nursing home facility in western New York State. PATIENTS: Nursing home residents and patient-care staff. MAIN OUTCOME MEASURE: Incidence of influenza-like illness among vaccinated versus unvaccinated nursing home residents and staff. RESULTS: Thirty-seven of 124 residents (attack rate = 30%) and 18 of 146 staff (attack rate = 12%) had an influenza-like illness. Staff illness began 16 days prior to onset among residents. Six cases of pneumonia and three influenza-related deaths occurred, all among the vaccinated residents. Ninety percent of the nursing home residents and 10% of the staff received the influenza vaccine prior to the outbreak. The calculated vaccine efficacies were minus 21% and plus 45% for residents and staff, respectively. CONCLUSION: While antigenic drift of the circulating influenza virus was the major factor in the apparent vaccine failure, the observed poor staff immunization rate (10%) and absence of surveillance which precluded the use of amantadine chemoprophylaxis suggest that the use of these strategies may be of importance in controlling influenza outbreaks in nursing homes. PMID- 1587977 TI - Outcomes of skilled cardiopulmonary resuscitation in a long-term-care facility: futile therapy? AB - OBJECTIVE: To assess whether cardiopulmonary resuscitation performed by in-house physicians is effective for long-term-care residents. DESIGN: Retrospective chart review. SETTING: Long-term-care facility with an intermediate care unit, skilled care unit, and a convalescent and assessment unit at a retirement community for veterans. PARTICIPANTS: All residents resuscitated from April 1987 to August 1990. All participants were male. The mean age was 75 years +/- 7.3 (range 42-93 years). MAIN OUTCOME MEASUREMENTS: Charts were abstracted for demographics, advanced directives information, information about the arrest, and post resuscitation course. RESULTS: Forty-five elderly residents underwent resuscitation during this period. Nine residents (20%) were successfully resuscitated, with seven dying within 24 hours of hospitalization. No residents survived to return to long-term care (95% CI, 0-7%). The diagnoses were consistent with age-related chronic disease. Seventeen (38%) arrests were witnessed. The predominant rhythm at onset of resuscitation was asystole. CONCLUSION: We conclude that cardiopulmonary resuscitation, even when performed by a trained and experienced physician and team, has limited benefit for elderly long-term-care populations. PMID- 1587978 TI - A population-based study of assessed applicants to long-term nursing home care. AB - OBJECTIVE: To examine the characteristics of all individuals assessed as requiring nursing home care arising from a population living within a defined geographical region and to study the manner in which they presented for assessment. DESIGN: Clinical assessment by a physician in geriatric medicine with the assistance of other disciplines. SETTING: Regional Geriatric Assessment Service. SUBJECTS: All persons recommended for nursing home care within the study period. RESULTS: The major diseases contributing to the need for nursing home care were organic brain disorders (60%) and stroke (32%). Dementia was present in 64% of cases; significant behavioral disturbance in 18%; severe communication disorders were frequent. The majority (86%) had been ill for greater than 1 year. The mode of presentation was acute in 9%, acute-on-chronic in 46%, and chronic in 45%. It was associated with significant differences in case characteristics including the location at the time of assessment, diagnoses, duration of illness, physical dependency, communication disorders, behavioral disturbance, and skilled nursing care requirements. CONCLUSIONS: These observations suggest that progression to nursing home care varies considerably. Strategies directed toward the prevention of institutionalization should be organized in recognition of these variations. PMID- 1587979 TI - Prognosis after hospital discharge of older medical patients with delirium. AB - OBJECTIVE: To determine survival, functional independence, and cognitive performance of older patients 2 years after an episode of delirium. DESIGN: Descriptive cohort study. SETTING: General medical wards of a teaching hospital. PATIENTS: Two hundred twenty-nine consecutive patients aged 70 years or older who had been community-dwelling prior to admission. Fifty patients met criteria for delirium (cases); these were compared to patients without delirium (controls). Two-hundred twenty-three patients survived hospitalization (46 cases, 177 controls) Of these, 92% were followed greater than or equal to 2 years. MAIN OUTCOME MEASURES: Vital status, place of residence, activities of daily living (ADL), and cognitive performance were determined by telephone interview of patients or care-givers 2 years after discharge. Independent community living was defined as survivorship outside of an institution and without dependence in any of four basic ADL (bathing, dressing, transfers, eating). RESULTS: Two-year mortality in the entire population was 39% for cases and 23% for controls (relative risk 1.82, 95% confidence interval 1.04-3.19). Delirium identified those patients at risk for loss of independent community living, even after adjustment for potential confounding variables (adjusted odds ratio 2.56, 95% confidence interval 1.10-5.91). Follow-up cognitive testing in a subset of patients with high baseline performance revealed a greater decline in performance among cases of delirium than controls (P = 0.023). CONCLUSIONS: Delirium identifies older patients at risk for mortality or loss of independence. Delirium may also identify patients at risk for future cognitive decline. PMID- 1587980 TI - Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly. AB - OBJECTIVE: To compare clinical status of elderly institutionalized subjects with asymptomatic bacteriuria and normal urinary antibody to those with elevated urinary antibody to the major outer membrane of Escherichia coli. DESIGN: Retrospective review. SETTING: Long term facility for the elderly. PARTICIPANTS: Convenience sample of 63 elderly subjects, 26% of those resident in the institution, aged 78.8 +/- 8.4 years with urine specimens collected and stored in 1987. MAIN OUTCOME MEASURES: Differences in clinical or functional status, demographic features, and outcome during 3-years follow-up between bacteriuric subjects with normal and elevated urine antibody. RESULTS: Thirteen subjects had no bacteriuria, and 12 had infrequent, intermittent bacteriuria; 38 (60%) had persistent bacteriuria, including four with frequent, intermittent infections. In the persistently bacteriuric group, 18 (47%) had persistently elevated urine antibody. There was no significant differences between bacteriuric residents with normal vs elevated urine antibody in clinical or functional status, age, duration of residence, or infecting organisms. However, 11 of 20 in the cohort with normal urine antibody were alive at 3 years compared to 3 of 18 with elevated urine antibody (P = 0.014). CONCLUSIONS: Elderly institutionalized subjects with persistent bacteriuria and elevated urine antibody have decreased survival compared to those with normal urine antibody. No differences in underlying illness or clinical course to explain this survival difference were identified. PMID- 1587981 TI - Rotator cuff tears in the elderly: a brief review of two cases. PMID- 1587982 TI - Addison's disease from tuberculosis in a centenarian. PMID- 1587983 TI - Life-threatening hyperphosphatemia and hypocalcemic tetany following the use of fleet enemas. PMID- 1587984 TI - Prostate cancer. AB - Clinically, prostate cancer (prostatic adenocarcinoma) is now the most frequently diagnosed cancer in males and the second leading cause of mortality due to cancer in the United States. However, because 75% of histologic prostate cancers remain functionally benign (will not metastasize and kill the patient), mass screening of the male population for the disease has become a hotly debated issue among urologists. The real challenge in the upcoming decade for geriatricians, though, will be to diagnose earlier in their course the prostate cancers which, if not treated, will metastasize and kill the patient and thus allow this subgroup of patients the opportunity to be treated more effectively. This review briefly discusses the etiology of prostate cancer, ways the disease may present, current treatments, depending on disease stage, screening in the diagnosis of prostate cancer, and quality of life issues important to patients confronted with the disease. PMID- 1587986 TI - Pessaries in the geriatric patient. AB - Pessaries have been used for centuries in the management of uterine prolapse. Although surgical repair has been popularized by surgeons and gynecologists for younger women with pelvic relaxation, pessaries remain a useful palliative strategy for patients who refuse surgery or represent higher operative risks. Despite the fact that pessaries are commonly used today, there is scant geriatric literature to describe their use among elderly patients. This article will review the indications and management of pessaries among elderly women with the goal of preventing complications and promoting investigation for their clinical application. PMID- 1587985 TI - An overview of allocation and rationing: implications for geriatrics. AB - Geriatricians are faced with increasing pressure from insurers and the public to control costs. At the same time, subspecialist colleagues, patients, and the courts often demand ever more costly high-technology interventions. This conflict will only intensify given the sustained increase in the percentage of GNP spent on medical care. A number of prominent biomedical ethicists and others have explored rationing of medical care services as one response to these concerns. This is the second in a series of articles in the Journal in response to the Oregon Health Decisions Initiative and is designed to provide (1) a brief ethical perspective on rationing and allocation; (2) an analysis of our present, largely implicit, approach to rationing and allocation; and (3) some suggestions that might move the United States closer to a more coherent and reasonable means of allocating and rationing health care. PMID- 1587987 TI - Placement of the demented elderly: special versus usual care in a nursing home. PMID- 1587988 TI - Rectovaginal fistula associated with fecal impaction. PMID- 1587989 TI - The prevalence and aeromedical certification considerations of contact lens use by civilian pilots. AB - Federal Aviation Regulations permit the routine use of contact lenses by civilian pilots to satisfy the distant visual acuity requirements for obtaining medical certificates. Specific information identifying the prevalence of contact lenses in the civil airman population is required to guide future medical certification decisions, policy changes, and education safety programs to aviation personnel. A descriptive, retrospective epidemiologic study was performed of active airmen by 5-year intervals for a 20-year period (1967-1987) using FAA data-bases and publications. The percentage of airmen who use contact lenses quadrupled during the study period. When stratified by class of medical certificate and age, the prevalence rates for airmen with first-class medical certificates and older airmen showed the largest increases. A summary is provided of aeromedical certification factors that an optometrist and/or ophthalmologist should consider while fitting an airman with contact lenses. The increasing use of contact lenses indicates a need for ongoing review of adverse changes and safety consequences for pilots. Key words: vision; contact lens; epidemiology; medical certification. PMID- 1587990 TI - Argon laser trabeculoplasty: a review. AB - A review of argon laser trabeculoplasty (ALT) indicates that it appears to be a viable tool in the treatment of many forms of open angle glaucoma. It effectively lowers intraocular pressure with few relative risks to the patient. Unfortunately, its pressure-lowering effects diminish with time. The primary risks of ALT are a transient rise in IOP (20 percent incidence) and the development of peripheral anterior synechia (20-46 percent incidence). The Glaucoma Laser Trial (GLT), a multi-institutional study, is currently evaluating the long-term effect of ALT. PMID- 1587991 TI - Treatment of esotropia with anomalous correspondence: a case report. AB - Management of anomalous correspondence in esotropia has been a controversial topic until recently. This case report presents a sequential treatment regimen which resulted in a successful binocular result for the patient. The implementation of overcorrecting prism, vision therapy/orthoptics, and extraocular muscle surgery is covered in the discussion of management strategies. PMID- 1587992 TI - Optometric management of optically induced consecutive exotropia. AB - A 5-1/2 year old black female initially presenting with a moderate angle esotropia and latent hyperopia developed a large angle constant exotropia 2 years after final correction of her refractive error. The occurrence of consecutive exotropia as a result of optical correction of hyperopia has been documented infrequently in the ophthalmologic literature and has rarely been mentioned in the optometric literature. While the overall risk for occurrence of this complication from correction of hyperopia may be small, it is a problem which may occur and can be avoided. Unfortunately, there is only limited information about the various risk factors that should be monitored to avoid the occurrence of an optically induced consecutive exotropia. What is available with regard to evaluation and management is scant, and there are no case reports emphasizing optometric management which includes the use of lenses, occlusion and vision therapy. The purpose of this paper is to present a case report of optically induced consecutive exotropia followed by a summary of the available information from the optometric and ophthalmologic literature. This combined information will aid optometrists managing these patients to avoid the occurrence of this problem and better understand the various management aspects when it does occur. PMID- 1587993 TI - Dependence of hypotensive effect of neuropeptide-Y 18-36 fragment on intact vagus nerves. AB - Effects of neuropeptide Y (NPY 2.35-4.7 nmol) and the fragment NPY 18-36 (3.6-36 nmol) were studied in anaesthetized rats before and after vagotomy for actions on blood pressure (a postjunctional action) and on the change in pulse interval evoked by stimulation of the cut, peripheral vagus nerve (a prejunctional action). In intact rats NPY increased blood pressure. Low doses of NPY 18-36 (2.3 4.7 nmol) also increased blood pressure slightly but higher doses only transiently increased blood pressure and this was followed by a prolonged decrease in blood pressure. In vagotomised rats NPY increased blood pressure and attenuated cardiac vagal action. In higher doses the presynaptic effect of NPY 18 36 was more marked than its pressor action. NPY 18-36 (3.6-36 nmol) also increased blood pressure and attenuated cardiac vagal action. Thus, we conclude that the hypotensive action of NPY 18-36 depends on the intact vagus nerves: in the vagotomised rat NPY 18-36 has similar biological activity to NPY, but with reduced potency. To examine further the mechanism of hypotensive action of NPY 18 36 arterial rings from the central artery of the rabbit ear were also tested for direct actions of the peptides. This preparation is also suitable for testing any potentiation of contraction evoked by injection of noradrenaline. Neither NPY nor NPY 18-36 caused direct constrictor action in concentrations up to 10 microM. NPY 18-36 had no relaxing effect on constricted arterial rings.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1587994 TI - The role of the sympathetic nervous system in promoting liver cirrhosis induced by carbon tetrachloride, using the essential hypertensive animal (SHR). AB - The effects of the sympathetic nervous system on liver injury induced experimentally by carbon tetrachloride (CCl4) were examined in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). It was found that the SHR had an elevated catecholamine (CA) content in the adrenal gland without any treatment, and fluorescence histochemistry also revealed dense adrenergic innervations in the liver. Moreover, the SHR showed greater sensitivity to CCl4 stimulation in the sympathetic nervous system than the WKY, resulting in a decreased hepatic blood flow in the acute stage and a depleted CA in the adrenal gland, a lowered blood pressure (BP) and a released non-esterified fatty acid (NEFA) from peripheral adipose tissue in the chronic stage. Upon repetition of the CCl4 treatments twice a week for 4 weeks, the liver injury was more severe in the SHR than in the WKY. Plasma glutamate-pyruvate transaminase (GPT) activity was increased in both strains but more significantly in the SHR than in the WKY. Histological examination of the liver in the SHR showed established cirrhosis, whereas only bridging fibrosis was seen in the WKY. These results suggest that the pathogenesis of the liver damage induced by CCl4 in the SHR, is attributable to the enhanced response of the sympathetic nervous system that releases massive amounts of CA which then lead to vasoconstriction and metabolic changes that promote liver damage. PMID- 1587995 TI - Evidence for dual components in the non-adrenergic non-cholinergic relaxation in the rat gastric fundus: role of endogenous nitric oxide and vasoactive intestinal polypeptide. AB - The effects of trypsin and arginine analogues, alone or in combination, on half maximal non-adrenergic, non-cholinergic (NANC) relaxation elicited by different pulse trains of electrical field stimulation were studied in the rat gastric fundus in order to investigate further the relative contribution of peptides and NO. Trypsin (1 microM) partially inhibited electrically-induced NANC relaxation especially when longer pulse trains were used. L-NOARG, L-NAME and L-NMMA, but not D-NOARG or D-NAME (3-300 microM) produced concentration-dependent inhibition of the electrically induced NANC relaxation. L-Arginine (L-Arg), but not D Arginine (D-Arg) (3.8 microM-3.8 mM) produced a concentration-dependent reversal of the inhibitory effect of L-NOARG IC50 (38 microM). Neither L-NOARG (38 microM) nor L-Arg (380 microM) influence submaximal relaxation induced by VIP (3 nM), isopropylnoradrenaline (10 nM), ATP (10 microM) or sodium nitroprusside (300 nM). Moreover L-NOARG (100 microM) did not influence neurally-induced VIP release. L NOARG inhibition of NANC relaxation was significant only when short pulse trains were used, while trypsin showed significant inhibition only of relaxation induced by longer pulse trains. These results suggest that the relaxation induced by the activation of the NANC inhibitory neurotransmission of the rat gastric fundus consists of at least two components, one trypsin-sensitive and the other trypsin resistant, to which VIP and NO contribute, respectively. PMID- 1587997 TI - Effects of age, heart rate, gender, tobacco and alcohol ingestion on R-R interval variability in human ECG. AB - To evaluate the possibly confounding effects of age, gender, heart rate, tobacco and alcohol ingestion on the coefficient of variation of the electrocardiographic R-R interval (CVRR), ECGs in the supine posture were obtained in 68 healthy men and 33 healthy women. The C-CVRSA and C-CVMWSA (two component CVs reflecting respiratory sinus arrhythmia and Mayer wave related sinus arrhythmia, respectively) were computed in each subject from component spectral powers using autoregressive spectral and component analyses. Results of multiple regression analysis indicated that age was inversely related to CVRR, C-CVRSA and C-CVMWSA in both sexes. Heart rate was positively related to C-CVMWSA in males. However, no significant difference in the CVRR, C-CVRSA or C-CVMWSA was found between males and females. The C-CVMWSA was not correlated with the C-CVRSA in either males or females. These data indicate that the CVRR, C-CVRSA and C-CVMWSA are affected by age and partly by heart rate; gender, moderate smoking or drinking habits might not strongly influence autonomic nervous system function. On the other hand, the C-CVRSA in the supine posture appears to be independent of the C CVMWSA. The positive relationship observed between the C-CVMWSA and heart rate suggests that the C-CVMWSA may be associated with sympathetic activity. PMID- 1587996 TI - Immunohistochemical, morphological and functional changes in the peripheral sudomotor neuro-effector system in elderly people. AB - Age-related changes in the human peripheral sudomotor neuro-effector system have been investigated in six 80-year-olds and six young adults. Histochemical and immunohistochemical studies on forearm skin biopsies showed diminished vasoactive intestinal polypeptide (VIP) and calcitonin gene related peptide (CGRP)-like immunoreactivity and a virtual absence of acetylcholinesterase in the elderly sudomotor nerve endings compared to the young. Reduced size of nerve bundles and decreased density of sympathetic nerve endings adjacent to the sweat glands of old people were shown by the neuronal marker, protein gene product (PGP 9.5), and by electron microscopy. Image analysis techniques were also used to demonstrate a marked regression in secretory coil size with age. Functional decrements accompanying the neurochemical and morphological changes in the neuro-effector system were measured in ten 80-year-olds by local quantitative nicotine axon reflex responses and compared with 12 young adults. These studies demonstrate marked regressive changes in both the nerve endings and target cells in old age and appear to express a significant loss of vigour in trophic interactions. PMID- 1587998 TI - Diminished contractile responses to neuropeptide Y of arteries from diabetic rabbits. AB - The vascular smooth muscle contractile response to neuropeptide Y (NPY), potassium, noradrenaline, histamine and serotonin was studied in circular segments of isolated vessels in vitro from rabbits with alloxan-induced diabetes mellitus. The injection of alloxan resulted in a marked and maintained increase in serum glucose as early as 1 week after treatment. Four vessel types were examined: abdominal aorta, and renal, left anterior descending coronary and middle cerebral arteries. There was no difference in the contractile response to histamine or serotonin between control and diabetic vessels. However, in the cerebral artery the contractile response to noradrenaline was reduced in the diabetic group, while in the aorta and the renal artery no significant differences were seen. Noradrenaline failed to evoke any contractile response in the coronary arteries in either group. NPY induced strong, concentration dependent contractions of coronary and cerebral arteries, but did not have any contractile effect per se in aorta or renal arteries, either in control or in alloxan-treated rabbits. The maximal contractile effect and the sensitivity to NPY was significantly less in diabetic coronary and cerebral vessels as compared to control. There was no difference in dilator effect of acetylcholine and substance P between the diabetic animals and the control group in any of the vessel types, indicating that the changed vascular responses to NPY and noradrenaline were not endothelium-dependent. In conclusion, the present study has shown that the postjunctional effects of NPY and noradrenaline in the peripheral sympathetic nervous system are selectively attenuated in this model of chronic diabetes. PMID- 1587999 TI - Enhanced muscle sympathetic nerve activity during sleep apnea in the elderly. AB - To examine how muscle sympathetic nerve activity (MSNA) becomes modified during sleep apnea in the elderly, we analyzed polysomnographic recording simultaneously with microneurographically recorded MSNA. Subjects were three healthy elderly males aged 72, 75, and 76. MSNA was suppressed with deeper non-REM sleep stages in these elderly subjects. In all three subjects, sleep apnea for 10 s or longer was observed during sleep of 00:00-06:00. During sleep apnea, MSNA was enhanced concomitantly with a blood pressure fall and a reduction in saturation rate of oxyhemoglobin. With the termination of sleep apnea, MSNA was maximally enhanced with a transient elevation of blood pressure. We conclude that sleep apnea induces an enhancement of MSNA, which may be responsible for hypertensive episodes during sleep. PMID- 1588000 TI - Hypovolemia induces Fos-like immunoreactivity in neurons of the rat supraoptic and paraventricular nuclei. AB - Immunoreactivities to Fos proteins were detected in numerous neurons in the supraoptic, paraventricular and accessory neurosecretory nuclei 1 h following withdrawal of 4-5 cc of blood from the rat femoral arteries. Few or no positive cells were observed in the same nuclei in sham-operated or control animals. It is concluded that hypovolemia induces c-fos expression in hypothalamic neurons known to be associated with blood volume/pressure regulation. PMID- 1588001 TI - Vasoactive intestinal peptide and neuropeptide Y coexist in non-noradrenergic sympathetic neurons to guinea pig trachea. AB - Vasoactive intestinal peptide (VIP) has been suggested to be a mediator of vagal inhibition of airway tone and it has been assumed that VIP-containing nerve fibres in the airway arise from intrinsic ganglia. We have used a combination of double- and triple-labelling immunohistochemistry, retrograde axonal tracing, organotypic culture and nerve lesion studies, to identify the origin and distribution of neurons containing immunoreactivity (IR) to VIP in guinea pig airway smooth muscle. We also investigated whether immunoreactivity to other neuropeptides coexisted with VIP-IR within these neurons. We found that all VIP IR nerve fibres in guinea pig tracheal smooth muscle also contained IR to neuropeptide Y (NPY) but not to tyrosine hydroxylase (TH), a marker for noradrenergic neurons. Both VIP-IR and NPY-IR were absent from nerve cell bodies in the tracheal plexus. After maintenance of isolated trachea in organotypic culture for 4 days, to allow degeneration of extrinsic nerve fibres, nerve fibres containing VIP-IR or NPY-IR were almost completely absent from tracheal smooth muscle. Of ganglia known to supply the trachea, coexistence of VIP-IR and NPY-IR was found only in cell bodies of the stellate ganglion. Retrograde tracing studies using the fluorescent tracer, DiI, confirmed that the stellate ganglion was the site of origin of neurons containing VIP-IR and NPY-IR supplying the airways. These neurons projected to the airways from the stellate ganglion both directly through the mediastinum, and via the cervical sympathetic trunk and vagus nerves. These results suggest that nerve fibres containing both VIP-IR and NPY-IR in the tracheal smooth muscle of the guinea pig are derived from non noradrenergic cell bodies in the stellate ganglion. The absence of VIP-IR from vagal post-ganglionic neurons suggests that VIP cannot be a mediator of vagal inhibitory transmission in tracheal smooth muscle of this species. PMID- 1588002 TI - Response of noradrenaline and dopamine to hypoxia and sympathectomy: evidence for an independent dopaminergic reactivity. AB - In order to assess the status of dopamine in the periphery, we submitted rats to sympathectomy (with guanethidine), to hypoxia, and to both, and measured the concentration and turnover of noradrenaline and dopamine in peripheral organs. Sympathectomy decreased noradrenaline content by 96-99% in all the organs tested. In contrast, dopamine content, which was decreased by 90% in the heart, was not significantly changed in the bladder or lungs. Based on dopamine decrease after guanethidine, and on dopamine:noradrenaline ratios in organs, we conclude that in the heart the dopamine is contained mostly in noradrenergic terminals. In other organs it appears to be contained in non-noradrenergic structures. These are found in: the bladder, stomach, lungs, and kidneys, in decreasing importance. We estimated the turnover of noradrenaline by measuring the decrease of its concentration after inhibition of tyrosine hydroxylase with alpha-methyl-p tyrosine. Among the five organs studied, the turnover of noradrenaline was increased by long-term hypoxia (10% O2, 15 days) in the heart only (+140%). An increase of sympathetic activity during hypoxia was also found in the kidneys and lungs as shown by the increase in turnover of dopamine that was suppressed by sympathectomy. Hypoxia induced large increases in dopamine concentration in the stomach and the lungs (70 and 190% respectively). These increases were not abolished by sympathectomy and we propose that they are related to a chemosensory function of dopamine-containing paraganglia in the stomach and the lung. PMID- 1588003 TI - Autonomic mechanisms in heart rate variability after isoproterenol-induced myocardial damage in rats. AB - The effect of isoproterenol-induced myocardial damage on heart rate variability was examined in conscious, unrestrained, male, Sprague-Dawley rats. We used power spectrum analysis of beat-to-beat heart rate to study the levels and interaction of sympathetic and parasympathetic neural influences on the heart. One day after isoproterenol (80 mg/kg s.c.), mean heart rate was significantly elevated when compared to controls (isoproterenol 413.9 b.p.m. +/- 7.7 S.E.M.; saline 368.8 b.p.m. +/- 12.8 S.E.M.; P less than 0.05), even though the low frequency and respiratory components of the power spectrum were not different between the two groups. By contrast, a week after isoproterenol administration, heart rate was normal; however, variability in low frequency and respiratory areas of the power spectrum was significantly increased suggesting an abnormal sympathovagal balance. An imbalance in autonomic regulation of cardiac automaticity could account for the 27% incidence of arrhythmias in rats given isoproterenol. These results indicate that autonomic responses associated with isoproterenol-induced myocardial ischemia differ from those in human and in animal models of myocardial infarction. PMID- 1588004 TI - Power spectrum analysis of heart rate fluctuations and respiratory movements associated with cooling the human skin. AB - A length of respiratory movement and instantaneous heart rate was divided into 32 segments to adopt computerized power spectrum analysis. An array of frequency spectrum across all the segments was then constructed to demonstrate sequential changes in the respiratory rhythm (0.4 Hz), low (less than 0.1 Hz) and high (0.2 0.4 Hz)-frequency components of heart rate fluctuations associated with lowering the skin temperature. A significant increase in the power for the low and high frequency components of heart rate fluctuations accompanying bradycardia occurred by cooling the face to 0 and 10 degrees C, while cooling the foot to 0 degrees C yielded a significant increase and decrease in the power for the former and latter component, respectively, without change in heart rate. The spectral power for respiratory movements was not altered by these stimuli. The maximal change in the power for low- and high-frequency components as well as in the heart rate during cooling the face and foot to 0 degrees C was found to correlate negatively with the relative resting magnitude of the respective parameter in the pre stimulus period. Similar relationship existed only with the power for low frequency component of heart rate fluctuations when lowering the temperature of foot to 10 degrees C. The power spectrum array employed in this study thus enabled us to estimate the effectiveness of skin cooling on the three hemodynamic parameters. PMID- 1588005 TI - Gastric reflex relaxation by colonic distension. AB - Previous studies in human volunteers have demonstrated an inhibition of gastric motility following painless rectal distension. In the present study we investigated, in anaesthetized rats, the effects of colonic distension on gastric tone and looked at certain aspects of the underlying nervous mechanisms. Changes in gastric volume were monitored continuously by a volumetric method. Colonic distension induced an immediate and pronounced gastric relaxation which lasted throughout the period of distension. The inhibition of gastric tone following colonic distension was abolished by hexamethonium or by bilateral cervical vagotomy. The selective adrenergic alpha 1 blocker, prazosin, the alpha 2 blocker, yohimbine, and the non-selective beta-blocker, propranolol, had no significant effect on gastric relaxation following colonic distension. Likewise, naloxone, an opioid receptor antagonist, did not significantly influence gastric reflex inhibition. It is concluded that colonic distension induced a non adrenergic inhibition of gastric tone mediated through the vagal nerves. Ganglionic receptors are also suggested to form part of the inhibitory pathway. PMID- 1588006 TI - Deficiency of sympathetic nervous system function in myasthenia. AB - The norepinephrine (NE) and epinephrine (E) responses to forearm ischemia were studied in 24 myasthenic patients and 22 subjects with lumbar disc disease (control group). In some of these myasthenic (11 cases) and control (11 cases) subjects the NE and E responses to orthostasis were also investigated. In controls both stimuli induced a rise in NE urinary excretion without significantly changing the E excretion. On the other hand, in myasthenic patients forearm ischemia and orthostasis were followed by an augmentation in E excretion, the NE excretion remaining unchanged or even undergoing a depression. In other myasthenic patients (10 cases) and subjects with lumbar disc disease (10 cases) NE and E responses to exercise were tested. The results were similar to those presented above: controls reacted to exercise by a rise in NE excretion, while myasthenic patients, by an augmentation in E excretion; the NE excretion underwent no change or even decreased after exercise in myasthenia. The obliteration of NE response to all three testing stimuli found in myasthenic patients may be considered as a sign of their sympathetic deficiency. In such patients the normal E discharge produced by forearm ischemia, orthostasis or exercise may be interpreted as a compensatory reaction, being probably the consequence of sympathetic deficiency. The noradrenergic deficit of myasthenic patients is ascribable to their cholinergic hyperactivity. PMID- 1588007 TI - Neurogenetic neurometabolic disease. PMID- 1588008 TI - CT and MRI of the brain in inherited neurometabolic disorders. AB - The incidence of many autosomal recessive neurometabolic disorders is very high in Saudi Arabia, probably as a result of the frequency of consanguineous marriages. Because our hospital is the main referral center for the entire Kingdom, we examine a large number of patients who have a wide spectrum of neurometabolic disorders. We add our experience and review the world literature. Though a specific diagnosis is radiologically possible in a few disorders, the diagnosis must always be verified biochemically. When the patient is referred from a pediatric neurologist with the diagnosis of neurometabolic disorder, the aim of the neuroradiologist is to determine the amount of brain damage present and to follow the response to given therapy. When the patient is referred with a nonspecific diagnosis, such as delayed development, the aim is to suggest the possibility of a neurometabolic disorder and to initiate further evaluation including possible therapy and genetic counseling. PMID- 1588009 TI - Saudi variant of multiple sulfatase deficiency. AB - We describe eight patients with multiple sulfatase deficiency (MSD, or Austin's disease) who differ phenotypically from classic neonatal-, childhood-, or juvenile-onset MSD. The age of onset was in childhood. The patients presented with somatic and facial features of mucopolysaccharidosis reminiscent of Maroteaux-Lamy and Morquio syndromes. They differed from classic MSD by the presence of corneal cloudiness, macrocephaly, severe dysostosis multiplex, and gibbus and the absence of ichthyosis, retinal degeneration, severe deafness, severe mental retardation, and dementia. The main neurologic presentation was cervical cord compression due to axis abnormalities. Despite neuroradiologic evidence of white-matter changes, neurologic presentation was not like metachromatic leukodystrophy. The sulfatase deficiencies were more marked than in the classic juvenile form of MSD, but less marked than in the classic childhood onset form of MSD. Steroid sulfatase activity was spared except in one patient. This Saudi variant of MSD accounts for 5% of all lysosomal storage diseases in the Cell Repository Registry of our Inborn Errors of Metabolism Laboratory. PMID- 1588010 TI - Treatment of inherited neurometabolic diseases: the future. AB - The past 10 years' experience with bone marrow transplantation from normal, immunologically compatible donors indicates its possible use in various neurometabolic diseases, particularly in a patient who has not suffered irreparable brain damage. This experience may be a prelude to treatment by somatic gene therapy. This can be applied as an autologous bone marrow transplant, grafting the patient's own stem cells inserted with the normal gene. Although somatic gene therapy will be relatively easy for tissues with dividing cells, its application to target tissues with little or no cell division may pose difficulties. Meanwhile, techniques for the preservation, culture, and grafting of fetal neurons in humans have been developed and have been used in the treatment of Parkinson's disease. These procedures could readily be transferred to the treatment of other neurodegenerative diseases that cause significant morbidity, but ethical, legal, and religious considerations must be taken into account. All these efforts promise novel and improved management of inborn neurometabolic errors. PMID- 1588011 TI - Biochemical heterogeneity of infantile central nervous system spongy degeneration. AB - Aspartoacylase, the enzyme whose activity is deficient in infantile central nervous system spongy degeneration (Canavan-Van Bogaert-Bertrand disease), is detected as an approximately 59-kD protein in the Sephadex G-200 filtration of normal fibroblast extracts. The enzyme activity in homogenates of fibroblasts is protected by leupeptin, a protease inhibitor. In the absence of leupeptin, 90% of aspartoacylase activity is lost. In some patients with infantile spongy degeneration, no activity (less than 2%) can be detected. In some other patients with residual activity in fibroblasts, two separate peaks of enzyme are eluted with molecular weight corresponding to approximately 59 and 19 kD. Aspartoacylase activity in this latter group is protected to the same extent by the presence of leupeptin. However, the elution of two peaks is independent of the presence of leupeptin. This study indicates biochemical heterogeneity in the pathogenesis of infantile spongy degeneration. PMID- 1588012 TI - Response of 6-pyruvoyl-tetrahydropterin synthase deficiency to tetrahydrobiopterin. AB - We have given tetrahydrobiopterin (BH4) in doses ranging from 2.5 to 20 mg/kg/day, each for a duration of 5 days to three patients with 6 pyruvoyltetrahydropterin synthase deficiency. As small a dose as 2.5 mg/kg/day BH4 reduced the blood phenylalanine to normal levels. However, the required dose of BH4 to reduce neopterin and to increase urine biopterin was 5 to 10 mg/kg/day, while 20 mg/kg/day was required for biopterin to appear in cerebrospinal fluid. The results suggest that BH4 effectively reduces endogenous neopterin synthesis. The dose of BH4 needed to normalize liver phenylalanine hydroxylase is one eighth to one fourth that required for normal neurotransmitter metabolism in the central nervous system. PMID- 1588013 TI - Heterogeneity of carboxypeptidase activity in infantile-onset galactosialidosis. AB - The clinical presentation and laboratory findings in seven patients with neonatal/infantile-onset galactosialidosis are presented. We detected no carboxypeptidase activity in two of these patients, while an enzyme with different apparent Km, or both Km and Vm, were found in five others. We could not establish a correlation between the biochemical characteristics of carboxypeptidase and the age of onset, progression, or other clinical features of galactosialidosis. PMID- 1588014 TI - Neurometabolic diseases at a national referral center: five years experience at the King Faisal Specialist Hospital and Research Centre. AB - Of 910 children under the age of 12 years referred to the national center, we were able to assign an etiology to 473 (52%). This group consisted of lysosomal storage diseases (32%), amino acid disorders (14%), organic acid disorders (16%), various chromosome abnormalities and syndromes with dysmorphia or brain dysgenesis (26%), and various other metabolic diseases (12%). While such amino acidemias as branched-chain amino acidemia (MSUD) in classic and intermediate forms (44%) and hyperphenylalaninemia (PKU) due to 6-pyruvoyltetrahydropterin synthase deficiency (6PTSD) (19%) were common, classic PKU was rare (16%). Methylmalonic acidemia (31%), 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (16%), and propionic acidemia (12%) were encountered more frequently than other types of organic acidemias. When compared to the number of referred Down's syndrome patients, the results suggested the birth of at least one infant with neurometabolic disease per 50 births. Five tribes of Saudi Arabia constituted 26% of the diagnosable neurometabolic diseases. Diseases such as MSUD, 6 PTSD, Sanfilippo syndrome type B, methylmalonic acidemia, homocystinuria, GM2 gangliosidosis Sandhoff variant, infantile central nervous system spongy degeneration (Canavan disease), and neuraminidase deficiency showed definite tribal occurrence. In addition, 32% to 42% of the definitely diagnosed, and 25% to 87% of patients with probable neurometabolic disease but without a definable etiology, had more than one sibling affected. It is concluded that the many rare autosomal diseases of Saudi Arabia are due to "founder effect" created by marriages occurring within tribal and extended family boundaries. PMID- 1588015 TI - GM1 gangliosidosis type 2 in two siblings. AB - A sister and brother, now aged 7 and 9 years, presented with developmental arrest, gait disturbance, dementia, and a progressive myoclonic epilepsy syndrome with hyperacusis in the second year of life. Then, spastic quadriparesis led to a decerebrate state. In the absence of macular or retinal degeneration, organomegaly, and somatic-facial features suggesting mucopolysaccharidosis, the presence of hyperacusis together with sea-blue histiocytes in bone marrow biopsies and deficient beta-galactosidase activity but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal enzyme assays constitutes the clinical-pathologic-biochemical profile of GM1 gangliosidosis type 2. This is a rare, late infantile onset, progressive gray-matter disease in which beta galactosidase deficiency is largely localized to the brain, though it can be demonstrated in leukocytes and cultured skin fibroblasts. It must be distinguished from the Jansky-Bielschowsky presentation of neuronal ceroid lipofuscinosis, mitochondrial encephalopathy, lactic acidosis, strokelike episodes (MELAS) and myoclonic epilepsy with ragged-red fibers (MERRF) syndromes, atypical presentations of GM2 gangliosidoses (Tay-Sachs and Sandhoff's diseases), primary sialidosis (neuraminidase deficiency), galactosialidosis, and Alpers' disease. PMID- 1588016 TI - Congenital muscular dystrophy with abnormal radiographic myelin pattern. AB - We report 11 children with a homogeneous clinical syndrome affecting both sexes, characterized by weakness at birth, slowly improving course, weakness of all muscle groups, arreflexia, elevated blood creatine kinase, normal nerve conduction velocity, dystrophic changes on muscle biopsy, and diffuse periventricular cortical white-matter abnormalities with sparing of corpus callosum, internal capsule, and brain stem. We compare them to 48 other previously reported similar cases and designate them as altered myelin radiographic pattern congenital muscular dystrophy (CMD), which is the same as occidental CMD. We compare them to the other presently accepted phenotypes: progressive Fukuyama CMD, Walker-Warburg or cerebral-ocular CMD, and Santavuori or muscle-eye-brain CMD. We suggest that the different phenotypes are alleles of the same gene, which regulates or expresses a structural protein required for muscle integrity, myelination, and formation of the cortex. Such phenotypic diversity has been established for mutations of Xp21 in X-linked muscular dystrophies. PMID- 1588017 TI - Coping with an affected birth: genetic counseling in Saudi Arabia. AB - Saudi parents who have received genetic counseling following the birth of a child affected by a neurometabolic disorder were interviewed during their visits to a specialist hospital. As is common in the West, understanding of heredity was often incompletely assimilated, and this was related to parental education level. Coping behaviors, however, were substantially different from those in the West. The wide range of attitudes recorded toward consanguineous marriage and future births was a reflection of the position of Saudi families in a society undergoing rapid change. PMID- 1588018 TI - Coincident neuraminidase and aspartoacylase deficiency associated with chromosome 9Q paracentric inversion in a Saudi family. AB - A large, consanguineous Saudi family with three members with sialidosis type 1 and five members with infantile central nervous system spongy degeneration of the brain (ICNSSD, or Canavan-Bertrand-van Bogaert disease) is described. The patients with sialidosis had normal aspartoacylase activity, while neuraminidase activity in the patients with ICNSSD was reduced. All patients had normal carboxypeptidase activity in their fibroblasts. In an additional member there was photic-induced epilepsy, but he had normal enzymes. Two of the patients and one normal brother, but not the parents, had pericentric inversion of chromosome 9q. We postulate that an unidentified gene function is responsible for varied expression of these neurodegenerative diseases in this family. PMID- 1588019 TI - Riyadh chromosome breakage syndrome: mental retardation with depigmentation of the skin and hair. AB - A 20-month-old infant with "silvery-blond" hair color, widespread confettilike depigmentation of the skin, and mental retardation was found to have, in lymphocytes and fibroblast cultures, increased spontaneous chromosome breaks and breaks induced by both mitomycin and gamma-irradiation. The sister chromatid exchange frequency was normal. This child probably represents a new chromosome breakage syndrome. PMID- 1588020 TI - A patient with propionic acidemia managed with continuous insulin infusion and total parenteral nutrition. AB - An infant newly diagnosed with propionic acidemic coma was managed successfully with total parenteral nutrition (TPN) and continuous infusion of insulin. The urinary excretion of 3-hydroxypropionic acid was reduced to 3% of the admission value in 4 days, gradually decreasing to 1.5% in 16 days. The treatment did not prevent a prolonged episode of thrombocytopenia. The infant tolerated TPN well, except for continued hyper-lactic acidemia (2 to 4 times normal). Metabolic acidosis and mild hyperammonemia recurred only when the patient had sepsis secondary to Candida albicans and Staphylococcus aureus infection. PMID- 1588021 TI - Dietary management of inborn errors of amino acid metabolism with protein modified diets. AB - This paper presents experiences encountered with protein-modified diets (PMD) in the management of 67 patients, aged 1 day to 14 years, followed in the Pediatric Nutrition Clinic in the past 5 years. All had inborn errors of amino acid metabolism: maple syrup urine disease (MSUD), 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) lyase deficiency, propionic acidemia (PPA), or methylmalonic aciduria (MMA). In early infancy, the diet prescription is frequently adjusted to search for the infant's tolerance level of restricted amino acids. The levels must be established when natural foods other than milk are added to the PMD. The amino acids restricted are leucine, isoleucine, and valine in MSUD; leucine in HMG-CoA lyase deficiency; and isoleucine, methionine, threonine, and valine in PPA and MMA. Efficacy of the PMD depends on accuracy in prediction of the restricted amino acid requirement and the willingness and ability of parents and patients to conform to its demands. PMID- 1588022 TI - Effective diameters of protein A-gold and goat anti-rabbit-gold conjugates visualized by field emission scanning electron microscopy. AB - High-voltage (15-30 kV) field emission scanning electron microscopy (FESEM) was used to evaluate the effects of gold particle size and protein concentration on the formation of protein-gold complexes. Six colloidal gold sols were prepared, ranging in diameter from 7.6 to 39.8 nm. The minimal protecting amounts (m.p.a.) of protein A and goat anti-rabbit antibody (GAR) were experimentally determined. Gold particles were conjugated at the m.p.a., one half the m.p.a., and ten times the m.p.a. for both proteins, and protein-gold complexes prepared for FESEM. The smallest colloidal gold particles required the most protein per milliliter of gold suspension for stabilization. Transmission electron microscopy was found to be the preferred method for accurate sizing of gold particles, whereas FESEM of protein-gold complexes permitted visualization of a protein halo around a spherical gold core. Protein halo width varied significantly with changes in gold particle size. Measurements of protein halos indicated that conjugation with the m.p.a. of protein A resulted in the thickest protein layers for all gold sizes. GAR conjugation with the m.p.a. again produced the thickest protein layers. However, GAR halos were significantly smaller than those obtained with protein A conjugation. The proteins used showed similar adsorption patterns for the larger gold particles. For smaller gold particles, proteins may act differently, and these complexes should be further characterized by low-voltage FESEM. PMID- 1588023 TI - [3H]-ouabain binding sites in rat brain: distribution and properties assessed by quantitative autoradiography. AB - The anatomic distribution of high- and low-affinity cardiac glycoside binding sites in the nervous system is largely unknown. In the present study the regional distribution and properties of these sites were determined in rat brain by quantitative autoradiography (QAR). Two populations of cardiac glycoside binding sites were demonstrated with [3H]-ouabain, a specific inhibitor of Na,K-ATPases: (a) high-affinity binding sites with Kd values of 22-69 nM, which were blocked by erythrosin B, and (b) low-affinity binding sites with Kd values of 727-1482 nM. Sites with very low affinity for ouabain were not found by QAR. High- and low affinity [3H]-ouabain binding sites were both found in all brain regions studied, including somatosensory cortex, thalamic and hypothalamic areas, medial forebrain bundle, amygdaloid nucleus, and caudate-putamen, although the distributions of high- and low-affinity sites were not congruent. Low-affinity [3H]-ouabain binding sites (Bmax = 222-358 fmol/mm2) were approximately twofold greater in number than high-affinity binding sites (Bmax = 76-138 fmol/mm2) in these regions of brain. Binding of [3H]-ouabain to both high- and low-affinity sites was blocked by Na+; however, low-affinity binding sites were less sensitive to inhibition by K+ (IC50 = 6.4 mM) than the high-affinity [3H]-ouabain binding sites (IC50 = 1.4 mM). The QAR method, utilizing [3H]-ouabain under standard conditions, is a valid method for studying modulation of Na,K-ATPase molecules in well-defined anatomic regions of the nervous system. PMID- 1588024 TI - Distribution of chymase-containing mast cells in human bronchi. AB - Mast cell chymase stimulates secretion from cultured airway gland serous cells and hydrolyzes bronchoactive peptides in vitro. To explore the likelihood of these interactions occurring in situ, we examined the distribution and concentration of chymase-containing mast cells near glands and smooth muscle of major human bronchi from eight individuals without known airway disease. Total airway mast cells and the subset of mast cells containing chymase were detected by staining for methylene blue metachromasia and chloroacetate esterase activity, respectively. The percentage of chymase-containing mast cells was found to differ strikingly among bronchial tissue compartments. Near glands, for example, the concentration of chymase-positive mast cells (640 +/- 120 cells/mm3) was 73 +/- 9% that of total mast cells (910 +/- 130 cells/mm3), whereas in smooth muscle the concentration of chymase-positive mast cells (450 +/- 200 cells/mm3) was only 14 +/- 4% that of total mast cells (2920 +/- 620 cells/mm3). Of all chymase containing mast cells in the airway subepithelium, 30 +/- 4% were located within 20 microns of submucosal glands. Although the percentage of chymase-containing cells varied, the absolute concentration of chymase-containing mast cells was similar in all compartments. These results reveal a differential distribution of mast cell subpopulations in human airway and suggest that mast cells containing chymase are near gland and smooth muscle targets. PMID- 1588025 TI - A technique for retrieving antigens in formalin-fixed, routinely acid decalcified, celloidin-embedded human temporal bone sections for immunohistochemistry. AB - The application of immunohistochemistry to routinely decalcified, celloidin embedded human temporal bone sections has been hampered because of antigen loss during processing of the specimens. To our knowledge, there has been no published report to date describing immunohistochemical staining of such tissues suitable for examination by light microscopy. Here we report a novel antigen retrieval technique which can be successfully used to stain a variety of antigens in routinely formalin-fixed, trichloroacetic acid-decalcified, celloidin-embedded human temporal bone sections. The new procedure reported here for decalcified human temporal bone tissues simply requires immersing slides for 30 min at room temperature in an antigen retrieval solution. A total of 60 decalcified, celloidin-embedded human temporal bone tissues were tested with monoclonal antibodies (MAb) to 15 different antigens. Of these, 12 MAb showed definite positive staining, while three were negative. This technique may prove very useful in studying the expression of various antigens by immunohistochemistry in formalin-fixed, acid-decalcified, celloidin-embedded tissues. PMID- 1588026 TI - Monoclonal antibody to a common antigen of secretory granule membranes: intracellular localization and recycling of the antigen after secretion. AB - Monoclonal antibody (MAb) 170-5 was generated to the secretory granule membrane of rat parotid acinar cells. The MAb recognized integral membrane glycoproteins (SG 170 antigen) localized on the luminal side of the secretory granules with N linked carbohydrates, molecular weights 92, 84, 76, 69, and 65 KD. Immunohistochemical studies indicated that the SG 170 antigen was found in the secretory granules of both exocrine and endocrine cells and in the lysosomes of various cells in the rat. Immunoelectron microscopy with immunogold revealed that the antigen was present on the membrane of the secretory granules, lysosomes, the Golgi vesicles, and condensing vacuoles in pancreatic and parotid acinar cells and in AR42J rat pancreatic tumor cells; the Golgi stacks exhibited no immunoreaction. The common localization of the antigen in the secretory granule membranes indicated that this antigen may play an essential role in regulated secretion. Employing HRP-labeled MAb 170-5, we followed the retrieval of the antigen after exocytosis in AR42J cells. The MAb was internalized specifically with antigen-mediated endocytosis. It was transported to endosomes, subsequently to the trans-Golgi network, and then packaged into secretory granules. However, the Golgi stacks revealed no uptake of the labeled antibody. PMID- 1588027 TI - Immunoelectron microscopy of carbonic anhydrase isozyme VI in rat submandibular gland: comparison with isozymes I and II. AB - Carbonic anhydrase (CA) was purified from the saliva of pilocarpine-treated rats by inhibitor-affinity chromatography, and its localization in the rat submandibular gland was studied by the indirect immunoperoxidase technique using a monoclonal antibody (MAb) raised against the enzyme. SDS-polyacrylamide gel electrophoresis of the CA VI gave three bands of 33, 39, and 42 KD. Enzyme digestion experiment showed that the 42 KD molecule was degraded into the 39 KD molecule and the 39 KD molecule into the 33 KD molecule. The cleavage of the 42 KD molecule was independent and that of the 39 KD molecule was dependent on endo beta-N-acetylglucosaminidase F. The 42 KD molecule was detected in the CA purified from the pilocarpine-treated but not the untreated salivary gland. The MAb recognized all the three components of the enzyme. Immunostaining for CA VI was seen in the cytosol and secretory granules of serous acinar cells and in the duct luminal contents. Staining specific for erythrocyte CA (CA I and CA II) was observed in the cytosol of the epithelial cells of granular, striated, and excretory ducts. Among these duct cells, the agranular varieties in the granular and excretory ducts were essentially devoid of the immunoreactivity. PMID- 1588028 TI - Metabolic capacity of individual muscle fibers from different anatomic locations. AB - We studied muscle fibers by quantitative biochemistry to determine whether metabolic capacity varied among fibers of a given type as a function of their anatomic location. Muscles were selected from both contiguous and diverse anatomic regions within the rats studied. The individual fibers, classified into myosin ATPase fiber types by histochemical means, were assessed for fiber diameters and analyzed for the activities of enzymes representing major energy pathways: malate dehydrogenase (MDH, oxidative), lactate dehydrogenase (LDH, glycolytic), and adenylokinase (AK, high-energy phosphate metabolism). We found that neither the average activities of each of the three enzymes nor the fiber diameters varied in Type I or Type IIa fibers selected from superficial to deep portions of the triceps surae of the hindlimb. However, the IIb fibers in the deep region of this muscle group had significantly greater oxidative capacity, less glycolytic capacity, and smaller diameters than the superficially situated IIb fibers. Type IIa fibers in lateral gastrocnemius, extensor digitorum longus, psoas, diaphragm, biceps brachii, superficial masseter, and superior rectus muscles were highly variable in both diameter and enzyme profiles, with a correlation between MDH activity and fiber diameter. Therefore, our results show that both intermuscular and intramuscular metabolic variations exist in muscle fibers of a given type. PMID- 1588029 TI - Immunochemical and immunohistochemical detection of S-100-like immunoreactivity in spinach tissues. AB - S-100 proteins represent a group of closely related acidic, calcium binding proteins originally isolated from the mammalian nervous system and later detected in non-neural cell types and in a wide variety of vertebrate and invertebrate species. The present study used immunochemical and immunohistochemical methods to extend the investigation of S-100 during phylogenesis to plant tissues. The presence of S-100-like immunoreactive material was detected in extracts of spinach (Spinacia oleracea L.) terminal buds and young leaves by the ELISA method and by Western blotting using different anti-S-100 rabbit antisera. Using the PAP method, serial sections of young spinach leaves treated with the same antisera exhibited an immunoreaction product that was confined to the cytoplasm and nucleus (but absent from the vacuoles) in meristematic, epidermal, and parenchymal cells. The present data enlarge the field of investigation of S-100 proteins in the search of the function(s) of S-100 in biological organisms. PMID- 1588030 TI - Ultrastructural localization of the major components of the extracellular matrix in normal rat nerve. AB - In this study we determined the ultrastructural distribution of the various components of the extracellular matrix (laminin, fibronectin, Type I, III, and IV collagens) of the normal peripheral nerve in adult rat. The localization of these macromolecules was investigated in basement membranes as well as in different areas of epi-, peri-, and endoneurium, by use of a pre-embedding immunoperoxidase method. PMID- 1588031 TI - The use of osmicated tissues for Lowicryl K4M embedding. AB - Tissue chopper slices of rat incisor, rat parotid gland, and chicken tibiae, fixed with 1% glutaraldehyde, were post-fixed with potassium ferrocyanide-reduced osmium tetroxide, dehydrated with methanol, and conventionally embedded in Lowicryl K4M at -20 degrees C. The tissues showed an ultrastructural appearance comparable with that of their Epon-embedded counterparts and, in particular, the Golgi apparatus was well defined. Furthermore, Lowicryl K4M-embedded osmicated tissues permitted both post-embedding lectin-gold cytochemistry and immunogold labeling. PMID- 1588032 TI - Improved methods for using glass coverslips in cell culture and electron microscopy. AB - For many applications, cells or tissue must be cultured on an optical surface of high quality. For such applications laboratories often prepare "special dishes," which are made by affixing a glass coverslip beneath a hole in a plastic petri dish bottom. In this report, we offer an improved method, using Parafilm as a dry mount adhesive, for the preparation of special dishes, and show that the resulting dish is non-toxic to neurons in culture. The Parafilm bond is stable at 60 degrees C, permitting electron microscopy resins to be poured directly into the dishes and cured. The glass coverslip can be readily removed from the cured resin mechanically. The techniques we describe offer time-saving and reliable improvements for the use of glass coverslips in cell culture and electron microscopy. PMID- 1588033 TI - An innovative coating technique for light and electron microscopic autoradiography. AB - We describe a modified nuclear emulsion coating technique for both electron and light microscopic autoradiography. We propose that by reversing the application of formvar film so that it adheres to and covers thin sections placed on grids, we have developed a technically accessible methodology that produces optimal conditions for the tracing of specific nuclear activity. A smooth, continuous base is formed over the sections on which a monolayer of evenly packed silver halide crystals can be applied by dip-coating. The same principle is applied to pre-stained 1-micron plastic sections of glass slides. We suggest that the application of formvar film over thin sections does not impede or interfere with the exposure of the emulsion by the labeled tissue. On the contrary, it virtually eliminates contamination and background radiation, enhancing the specificity and quality of resolution at even low magnifications. This technical modification, which facilitates the application of the emulsion, could render electron microscopic autoradiography a routine laboratory procedure, allowing for easily reproducible results and quantitative evaluation. At the light microscopic level, this technique prevents chemical fogging caused by certain stains, and thus allows routine pre-staining before coating with emulsion. PMID- 1588034 TI - Combined use of silver staining of the retrograde tracer WGAapoHRP-Au and pre embedding immunocytochemistry for electron microscopy: demonstration of dopaminergic terminals in synaptic contact with striatal neurons projecting to the substantia nigra in the rat. AB - We investigated the applicability of the pre-embedding immunoperoxidase technique to WGAapoHRP-Au retrograde tracing. After injection of the tracer into the substantia nigra of rat, the brain was fixed and cryostat sections were immunostained for dopamine. The sections were osmicated and silver-stained to amplify the colloidal gold particles. Products of both the immunoperoxidase staining and the silver staining could be detected and distinguished by electron microscopy at low magnification. The ultrastructure was so well preserved that synaptic characteristics could be investigated. Dopaminergic terminals were demonstrated to synapse with striatal neurons projecting to the substantia nigra. PMID- 1588035 TI - Processing of exogenous liposome-encapsulated antigens in vivo generates class I MHC-restricted T cell responses. AB - Acid-sensitive liposomes have been developed for cytosolic delivery of encapsulated substances. We now demonstrate delivery of liposome-encapsulated Ag into the class I MHC Ag processing pathway in peritoneal macrophages in vitro using several types of acid-sensitive liposomes, including those composed of dioleoylphosphatidylethanolamine (DOPE)/palmitoylhomocysteine, DOPE/cholesterol hemisuccinate, DOPE/dioleoylsuccinylglycerol, and DOPE/dipalmitoylsuccinylglycerol. Our previous studies showed that acid-resistant liposomes (dioleoylphosphatidylcholine/dioleoylphosphatidylserine) did not engender class I-mediated presentation in vitro. However, in vivo immunization with OVA encapsulated in acid-resistant as well as acid-sensitive liposomes generated class I MHC-restricted T cell responses, as determined by subsequent in vitro cytotoxicity assays using OVA-transfected target cells. Target lysis by these cells was OVA- and class I MHC (Kb)-specific. This response was not generated by immunization with equivalent amounts of soluble OVA. Thus, a pathway for in vivo class I processing of Ag encapsulated in acid-resistant liposomes has been missed in vitro, perhaps because it is dependent on specific populations of APC or interactions between cells that have not been reconstituted in vitro. This pathway may explain the ability of many exogenous particulate Ag (liposomes, bacteria, parasites, and mammalian cells) to generate class I MHC-restricted T cell responses. PMID- 1588036 TI - Perforin expression in human peripheral blood mononuclear cells. Definition of an IL-2-independent pathway of perforin induction in CD8+ T cells. AB - Perforin gene expression upon in vitro stimulation was studied at the mRNA level in normal human PBMC and in subpopulations. Freshly isolated PBMC express low levels of perforin mRNA. Increased perforin expression is rapidly induced by the calcium ionophore A23187 and by rIL-2. Phorbolesters (PMA), by comparison, are poor inducers of perforin RNA. Perforin induction by Ca-ionophore, unlike granzyme 2 and IL-2 induction, did not synergize with phorbolesters in PBMC or in purified T cells. Instead, perforin mRNA induction by A23187 in purified T cells requires the presence of adherent cells. Ca-ionophore plus adherent cell-induced perforin occurred in CD8+ T cells and was abolished by depletion of CD8+ T cells but not by depletion of CD4+ T cells. Adherent cells alone did not express perforin under any condition. Perforin mRNA induction by both A23187 and by rIL-2 is independent of de novo protein synthesis. The half-life of perforin mRNA induced by either stimulus is approximately 100 min. Cyclosporin A completely abrogates perforin induction by A23187 but only slightly inhibits the effect of rIL-2 on perforin mRNA expression. These data show that A23187 activates perforin gene expression in CD8+ cells by an IL-2-independent pathway and that the molecular mechanism of perforin expression may be different from the one induced by IL-2. Granzyme 2 (human leukocyte protease-HLP, homologous to murine granzyme B) mRNA expression was studied in comparison to perforin. Granzyme 2 in contrast to perforin responds to the synergistic action of phorbolester and Ca-ionophore in PBMC. In addition, the kinetics of the induction of granzyme and perforin mRNA, by various signals are different. Our data suggest that situations in vivo may exist that allow perforin expression in CD8+ cells in the absence of cytokines by a combination of Ca signals and accessory receptor ligation. The same signals may not be sufficient for granzyme 2 expression in any T cell subpopulation. PMID- 1588037 TI - Differential regulation of voltage- and calcium-activated potassium channels in human B lymphocytes. AB - The expression and characteristics of K+ channels of human B lymphocytes were studied by using single and whole-cell patch-clamp recordings. They were gated by depolarization (voltage-gated potassium current, IKv, 11-20 pS) and by an increase in intracellular Ca2+ concentration (calcium-activated potassium current, IKCa, 26 pS), respectively. The level of expression of these channels was correlated with the activational status of the cell. Both conductances are blocked by tetraethylammonium, verapamil, and charybdotoxin, and are insensitive to apamin; 4-aminopyridine blocks IK, preferentially. We used a protein kinase C activator (PMA) or antibodies to membrane Ig (anti-mu) to activate resting splenocytes in culture. Although IKv was recorded in the majority of the resting lymphocytic population, less than 20% of the activated cells expressed this conductance. However, in this subset the magnitude of IKv was 20-fold larger than in resting cells. On the other hand, IKCa was detected in nearly one half of the resting cells, whereas all activated cells expressed this current. The magnitude of IKCa was, on average, 30 times larger in activated than in nonactivated cells. These results probably reflect that during the course of activation 1) the number of voltage-dependent K+ channels per cell decreases and increases in a small subset and 2) the number of Ca(2+)-dependent K+ channels per cell increases in all cells. We suggest that the expression of functional Ca(2+)- and voltage activated K+ channels are under the control of different regulatory signals. PMID- 1588038 TI - Isotype-restricted hyperimmunity in a murine model of the toxic oil syndrome. AB - The toxic oil syndrome is characterized by IgE elevation and eosinophilia, as well as scleroderma-like skin manifestations and other symptoms of autoimmune disease. Fatty acid anilides, found in large amounts in adulterated cooking oil, were suspected to be the etiologic agent in this disease. The capacity of oleic acid anilide to induce features of autoimmunity in vivo was investigated. B10.S mice were continuously treated i.p. with oleic acid anilide for 6 wk by using osmotic pumps. A significant increase in IgE and IgM serum levels was observed after 1 to 3 wk; subsequently five of six mice developed IgG1 levels 3.5- to 10 fold higher than the controls. Anilide-treated mice developed splenomegaly with a 2.1- and a 3.5-fold increase in IgM- and IgG-bearing splenocytes, respectively, and a 5.6- and 29-fold elevation in functional IgM- and IgG-secreting cells, respectively. Increased serum levels of predominantly IgM antibodies to histone, denatured DNA, and DNP as well as rheumatoid factor were detected. In vivo expression in the spleen of 10 cytokine genes was also examined, and mRNA encoding IL-1 beta and IL-6 were significantly elevated in splenocytes of anilide treated mice. The enhanced Ig production suggests that anilide induced a cytokine mediated polyclonal activation of B cells. Elicitation of IgM antibodies to denatured forms of autoantigens indicates that anilide treatment partially broke autoimmune tolerance in these mice. Anilide-treated mice may be a useful animal model for further exploring the mechanism and pathogenesis of systemic autoimmunity in the toxic oil syndrome. PMID- 1588039 TI - Characterization and sequencing of a 40-amino-acid peptide from human thyroglobulin inducing experimental autoimmune thyroiditis. AB - We previously demonstrated that: a) a cytotoxic T cell hybridoma (HTC2) was able to induce lysis of syngeneic macrophages pulsed with either porcine thyroglobulin (pTg) or the tryptic fragments (TF) from pTg less than 10 kDa (M(r)) and that b) these low M(r) pTg TF included pathogenic epitopes because their injection into CBA/J mice induces thyroid lymphocytic infiltration typical of experimental autoimmune thyroiditis. Therefore the biochemical analysis of the TF preparation from pTg less than 10 kDa M(r) was undertaken and the characterized peptides were tested for their ability to be recognized or not by HTC2 cells. The sequencing of the selected peptides showed a 70% sequence homology with a portion of human thyroglobulin (hTg). The lack of a published sequence of pTg led us to synthesize a 40-amino acid peptide (F40D) similar to that portion of hTg. This F40D peptide was able to generate lymphocytic infiltrations in CBA/J mice thyroid glands, as was the native pTg molecule. Although the lymphocytic infiltrations were similar in the pTg or F40D-immunized mice, auto-antibodies to pTg or to hTg were only detectable in mice immunized with pTg. In contrast, autoantibodies levels to F40D peptide were significantly increased in serum from mice in which EAT had been induced by the F40D peptide. This highly hydrophobic peptide shows a M(r) of 4,492 kDa; it is located at the end of the second-third of the thyroglobulin molecule and up to now represents a unique sequence from the hTg molecule inducing experimental autoimmune thyroiditis. PMID- 1588040 TI - Anti-tumor necrosis factor antibodies suppress cell-mediated immunity in vivo. AB - Rabbit anti-murine TNF-alpha antibodies were administered in vivo to mice to evaluate the role of TNF-alpha in T cell-mediated immunity. Anti-TNF suppressed the in vivo development of contact sensitivity to the hapten TNP in a dose dependent fashion. Similarly anti-TNF suppressed the in vivo priming for TNP specific CTL. Control antibodies did not suppress cell-mediated immunity, whereas purified murine rTNF-alpha neutralized the antibody activity. Antibody therapy was effective during the afferent or priming limb of immunity, but could not inhibit the response if administered during the efferent limb. FACS for CD2, CD3, CD4, and CD8 T, B, and NK cell surface markers demonstrated no major change in the distribution of splenic lymphoid cell populations in animals pretreated with anti-TNF antibody. These results suggest that anti-TNF antibody may be interfering with soluble cytokines rather than with cell surface TNF causing depletion of cell populations. In vitro analyses also showed that anti-TNF has minimal inhibitory effects on secondary (secondary CTL) or strong primary (primary CTL, alpha CD3, MLR) responses, even though these in vitro cultures produce TNF mRNA as shown by polymerase chain reaction amplification. Although anti-TNF antibody did not affect the above responses, primary interactions are strongly inhibited in vivo. These findings suggest that TNF is important during afferent, priming events in immunity and that inhibition of TNF receptor-ligand interactions may alter immunity early in a response. Conversely such inhibition is ineffective later in a response, perhaps due to the ability of multiple other receptor-ligand pathways to bypass TNF. PMID- 1588041 TI - IL-4 induces IL-2 receptor p75 beta-chain gene expression and IL-2-dependent proliferation in mouse T lymphocytes. AB - T and B cells exhibit complex responses to the combination of IL-2 and IL-4, each of which can act as a growth or differentiation factor for lymphocytes under certain circumstances. To characterize better the mechanism by which these cytokines interact, mRNA levels of the signal-transducing p75 beta-chain of the IL-2R were analyzed. These studies show that IL-4 increases expression of the IL 2R beta-chain in mouse splenic B and T cells, and the response of B cells was potentiated by concurrent cross-linking of surface Ig. Kinetic analysis of the IL 2R beta response showed a slow onset but maintenance of peak levels of expression between 10 and 24 h. These data indicate that the pathways involved in the lymphocyte response to IL-4 differ for IL-2R and IL-4R, and that the induction of IL-4R precedes the increase in IL-2R. The effect of IL-4 on IL-2R beta mRNA levels was mediated in part by an increase in the rate of gene transcription, and was associated with increased IL-2 binding in the absence of any change in IL-2R alpha levels. In addition, IL-4 increased the level of IL-2R beta expression in thymocytes. Proliferation assays demonstrated that pretreatment of splenic T cells with IL-4 led to a substantial increase in IL-2-dependent proliferation. These results are consistent with a mechanism by which IL-4 can prime T cells and certain thymocytes for responsiveness to IL-2 by increasing IL-2R p75 chain gene expression, independent of general T cell activation. PMID- 1588042 TI - Assembly and transport properties of invariant chain trimers and HLA-DR-invariant chain complexes. AB - The MHC class II-associated invariant chain behaves as a resident endoplasmic reticulum protein in the absence of class II molecules. In humans, two predominant forms exist; one, p35, differs from the other, p33, by an N-terminal cytoplasmic extension of 16 amino acids that contains a strong endoplasmic reticulum-retention signal. Here we show that one mechanism for retention of p33 is its association with p35 in mixed invariant chain trimers. However, even for p33 homotrimers transport from the endoplasmic reticulum is inefficient. In an MHC class II-positive B cell line, the formation of invariant chain trimers is rapid and is the first intermediate in the assembly of a nine-chain alpha beta invariant chain complex. With time, three higher molecular weight complexes are progressively formed. These correspond to an invariant chain trimer with one alpha beta dimer, two alpha beta dimers, and three alpha beta dimers, respectively. No free alpha beta dimers are detectable early in biosynthesis. However, beginning at 2 h of chase, alpha beta dimers begin to appear concomitant with the disappearance of the completely assembled alpha beta-invariant chain complex. This conversion is virtually complete by 4 h, and presumably reflects the proteolytic degradation of the invariant chain component of the alpha beta invariant chain complex and the generation of endosomal alpha beta dimers capable of binding antigenic peptides. PMID- 1588043 TI - Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. AB - Airway damage secondary to eosinophil activation is thought to contribute to the development of asthma. Using the fluorescent dye FURA-2 to measure the concentration of cytosolic calcium, we found that supernatants from anti-IgE stimulated human lung mast cells increased cytosolic calcium in human eosinophils. We then examined the major mast cell mediators (histamine, PGD2, platelet-activating factor (PAF), eosinophil chemotactic factor of anaphylaxis (ECF-A), leukotriene (LT)C4 and LTB4) for their ability to increase cytosolic calcium in eosinophils. We found that both PAF (5 x 10(-9) to 5 x 10(-6) M) and PGD2 (two of five donors responsive at 1 x 10(-9) M) were potent stimuli for calcium mobilization. LTB4 (10(-8), 10(-7) M) and histamine were also active, although higher concentrations of histamine were required to see a response (3 x 10(-7) to 10(-5) M). LTC4, val-ECF-A, and ala-ECF-A were inactive. The effects of PGD2 and histamine were specific for eosinophils, although LTB4 and PAF increased calcium in both neutrophils and eosinophils. The histamine-induced increase in intracellular calcium was not blocked by the H1 or H2 antagonists pyrilamine or cimetidine (10(-4) M), respectively; however, the response to 10(-6) M histamine was completely blocked by the specific H3 antagonist thioperamide (10(-6) M). To evaluate the relative contribution of these stimulatory mast cell mediators on the calcium mobilizing activity in supernatants from anti-IgE-stimulated human lung mast cell (HLMC), we examined the effect of supernatants from HLMC pretreated with indomethacin and/or the 5-lipoxygenase pathway inhibitor MK886. These supernatants were added to FURA-2-loaded eosinophils that had been preincubated with thioperamide and/or the PAF antagonist WEB-2086. We found that the increase in eosinophil calcium in response to supernatants from anti-IgE stimulated-HLMC was totally inhibited only when the mast cells were challenged in the presence of indomethacin and MK886, and the eosinophils were preincubated with thioperamide. WEB-2086 had little effect. When we examined the effect of these mediators on eosinophil secretory function, we found that PGD2 (not histamine) primed eosinophils for enhanced release of LTC4 in response to the calcium ionophore A23187. We conclude that the activation of eosinophils by PGD2 and other mast cell products may contribute to airways inflammation that is characteristic of asthma. PMID- 1588044 TI - Apoptosis in human eosinophils. Programmed cell death in the eosinophil leads to phagocytosis by macrophages and is modulated by IL-5. AB - Eosinophils are believed to injure tissues in a variety of allergic disease by virtue of their highly histotoxic contents and metabolites. They are readily observed in tissues during the allergic response yet the mechanisms governing the duration of tissue residence and route of removal remain obscure. We have previously reported in vitro and in vivo evidence that neutrophils undergo apoptosis (programmed cell death) and are recognized and ingested as intact cells by macrophages. We report that eosinophils, purified from the peripheral blood of asymptomatic healthy atopics, undergo apoptosis in vitro. After 72 to 96 h in culture, 57.0 +/- 6.2% (mean +/- SE) of the eosinophil population showed characteristic morphologic changes of apoptosis. Electrophoresis of the DNA from these cells demonstrated the typical "ladder" pattern of internucleosomal DNA cleavage, the hallmark of apoptosis-associated endonuclease activation. The rate of eosinophil apoptosis, slower than that reported for neutrophils, was delayed (by 80 +/- 6 h) in the presence of recombinant human IL-5, a cytokine previously reported to prolong eosinophil life in vitro but not known to modulate apoptosis. Aged, apoptotic eosinophils, but not fresh or aged preapoptotic eosinophils, were recognized and ingested as intact cells by macrophages. Apoptosis and ingestion by macrophages may represent a mechanism whereby the tissue longevity and removal of eosinophils is controlled. PMID- 1588045 TI - HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. AB - The mechanism by which HLA-B27 confers genetic susceptibility to the seronegative spondyloarthropathies ankylosing spondylitis, Reiter's syndrome, and reactive arthritis, is not well understood. The current concept of an extraarticular bacterial infection functioning as the triggering event in a genetically susceptible host suggests the possibility of direct microbial-MHC interaction. We have addressed the role of HLA-B27 in microbial-host cell interaction by examining invasion by putatively arthritogenic gram-negative bacteria. Target cells used were murine L cells transfected with HLA-B27, HLA-A3, HLA-A2, HLA B44, HLA B18, or pSV2neo vector alone. Relative to the pSV2neo control and the HLA-A3 transfectant, HLA-B27-transfected cells demonstrated a consistent decrease in invasion for each of the following pathogens: Salmonella typhimurium (45 +/- 2% decrease), Shigella sonnei (53 +/- 13% decrease), Shigella flexneri (45 +/- 5% decrease), and enteroinvasive Escherichia coli (57 +/- 8% decrease). This decrease was specific for the HLA B27-transfected L cells and was not observed in the other B allele transfectants. The decreased invasion in the HLA-B27 transfectants is not the result of either altered endogenous mouse class I expression as a result of human class I transfection or increased intracellular bacterial killing within the B27 transfectants. There was an inverse relationship between the amount of surface expression of HLA-B27, as measured by FACS, and the degree of invasion. Blocking of surface B27 Ag with anti-B27 mAb augmented bacterial invasion in the B27 transfectants. These studies demonstrate a novel bacterial-B27 interaction that may have relevance to the pathogenesis of B27 related arthritis. PMID- 1588047 TI - IL-10 synergizes with IL-4 and transforming growth factor-beta to inhibit macrophage cytotoxic activity. AB - After activation with IFN-gamma, thioglycollate-elicited murine peritoneal macrophages kill schistosomula of Schistosoma mansoni in vitro by an L-arginine dependent mechanism which involves the production of reactive nitrogen oxides (NO). In the present study we demonstrate that the regulatory cytokines IL-10, IL 4, and transforming growth factor-beta (TGF-beta) are potent inhibitors of this extracellular killing function of activated macrophages. Each cytokine was found to suppress killing of schistosomula in a dose-dependent fashion. The activity of IL-10 was not permanent, because subsequent treatment with additional IFN-gamma 2 to 6 h later reversed the inhibition of macrophage larval killing. More importantly, the combination of suboptimal levels of any two of these three cytokines was found to give a potent synergistic suppression of schistosomulum killing by IFN-gamma-treated macrophages. Similarly, IL-10, IL-4, or TGF-beta alone blocked the production of NO, and when used in combination these cytokines exhibited an enhanced inhibitory effect on nitrite production. Macrophage mediated killing of schistosomula through the generation of NO has been shown previously to be a major effector mechanism of schistosome immunity. The results presented here suggest that the suppression of this mechanism by induction of the regulatory cytokines IL-10, IL-4, and TGF-beta, which are known to be produced during schistosome infection, may be an important strategy used by the parasite to evade macrophage-mediated immune destruction. PMID- 1588046 TI - Vasoactive intestinal peptide stimulates T lymphocytes to release IL-5 in murine schistosomiasis mansoni infection. AB - In murine schistosomiasis, granulomas form around ova deposited in the liver and intestines of infected mice. The granulomas have eosinophils that produce vasoactive intestinal peptide (VIP) and T cells that display VIP receptors. IL-5 is a lymphokine important for the development and maturation of eosinophils. It seemed plausible that VIP, released from eosinophils, may interact with lymphocyte VIP receptors and modulate IL-5 production as part of a feedback regulatory circuit. Thus, we determined whether granuloma T cells make IL-5 and whether VIP modulates IL-5 production. Isolated granuloma cells enriched for T lymphocytes spontaneously released IL-5. Culture of these cells in the presence of VIP increased IL-5 secretion. Spleen cells were also studied. Spleen cells from infected mice did not spontaneously release IL-5 or express IL-5 mRNA and VIP did not stimulate these resting spleen cells to produce this IL. However, these cells did express IL-5 mRNA and secreted IL-5 in response to Con A or soluble egg Ag. VIP could not appreciably modulate IL-5 release when cells were cultured with VIP and the Ag or mitogen. Spleen cells washed free of Con A ceased IL-5 secretion within 24 h. These preactivated splenic T cells resumed vigorous IL-5 secretion in response to either Con A or VIP. Yet only Con A prominently induced IL-5 mRNA expression. VIP was an effective stimulus at concentrations equal to or above the kDa of the VIP receptor on both splenic and granuloma T cells (10(-8) M). It is concluded that, in murine schistosomiasis, VIP invokes IL 5 release from activated T cells that are not undergoing immediate TCR stimulation. PMID- 1588048 TI - High serum IL-6 level reflects susceptible status of the host to endotoxin and IL 1/tumor necrosis factor. AB - Patients with high level of serum endotoxin did not necessarily develop into lethal shock, whereas some patients died of septic shock even when their serum endotoxin levels were low. These results indicate that limiting factor which determines the host to be endotoxin shock principally depends on the host susceptibility to endotoxin instead of serum endotoxin level. To understand this susceptible status of the host to endotoxin, we used Propionibacterium acnes primed mouse endotoxin shock model. We found that P. acnes-primed mice responded to low dose of LPS by enhanced production of IL-1 and TNF. And such mice were highly susceptible to the lethal shock inducing effect of IL-1 and/or TNF, which also induced high level of serum IL-6 in these mice. Therefore, measurement of serum IL-6 level provides us with the information of the preceding exposure of the host to either LPS or IL-1 and/or TNF and the highly susceptible status of the host to these stimuli. Based on these results obtained from animal model, we investigated the relationship between serum IL-6 levels and serum endotoxin levels in the patients with malignant hematologic disorders. We found that these patients fell into two groups; an endotoxin susceptible group, equivalent to P. acnes-primed mice, showing high level of serum IL-6 with low level of serum endotoxin, and a nonendotoxin susceptible group, equivalent to P. acnes-nonprimed mice, showing low or undetectable level of serum IL-6 with high level of serum endotoxin. We propose that the measurement of serum IL-6 level in the patients positive for endotoxin is a useful tool in evaluating diagnosis and prognosis of endotoxin shock. PMID- 1588049 TI - Specific VDJ gene combinations contribute to the specificity of memory antibodies to the phosphorylcholine hapten. AB - Based on their fine specificity, two groups of antibodies against the phosphorylcholine (PC) hapten have been described. Group I antibodies react predominantly with the PC moiety of the hapten and group II are directed against the entire hapten including the azophenyl spacer to the protein carrier. We have analyzed the VH gene segment utilization of hybridomas from the memory response to PC by Southern blot analysis and nucleotide sequencing of the functional VDJ rearrangements. Three main specificities of anti-PC antibodies could be distinguished. Anti-PC hybridomas with group I fine specificity utilize the VH1 DFL 16.1-JH1 rearrangement. A major portion of group II antibodies recognized the phenyl-PC part and expressed the same VH1 gene in combination with a member of the SP2 family and JH1 or JH2. The other anti-PC antibodies either used the PJ14 DFL16-JH3 rearrangement in combination with a lambda 1 L chain or a member of the VGam3.8 VH family rearranged to the DFL16.1 and the JH3 gene segments. The PJ14 and VGam3.8 V gene expressing antibodies were directed to the phenyl group and were either not or barely inhibitable by PC chloride. Thus, specific VDJ gene combinations contribute to the fine specificity of antibodies in the memory response to the PC hapten. The use of the S107, Q52, and VGam3.8. VH gene families, together with FL16.1 or SP2 D segments and JH1, JH2, or JH3 results in different fine specificities to the PC, phenyl-PC, or the azophenyl moiety of the PC hapten. These fine specificities of the memory response use V, D, and J segments of the initial T15Id+ response in combination with gene segments usually related to phenyl specificity. PMID- 1588050 TI - Usage of primary cells to delineate IFN-gamma-responsive DNA elements in the HLA DRA promoter and to identify a novel IFN-gamma-enhanced nuclear factor. AB - The IFN-gamma regulation of the HLA-DRA gene was examined in a primary cell type, the astrocyte. Site-specific mutagenesis of the DRA promoter reveals that three known sequences, S, X, and Y, are required for an optimal IFN-gamma response. Specifically for the X sequence, the X1, but not the X2, site is involved in IFN gamma regulation of HLA-DRA in the astrocyte. Most interesting, a novel IFN-gamma enhanced protein (IFNEX) with specificity for the X element has consistently been observed in nuclear extracts made from primary astrocytes. The correlation of the functional importance of X1 in IFN-gamma-regulated DRA expression and the enhancement of IFNEX by IFN-gamma strongly suggests that IFNEX may play a crucial role in IFN-gamma-regulated class II MHC gene expression. PMID- 1588051 TI - Mechanism of lipopolysaccharide-mediated transcriptional enhancement of the mu gene. AB - LPS induces both B cell proliferation and differentiation to Ig secretion. By treating stimulated cells for a brief period with staurosporine, and inhibitor of protein kinase C, it is possible to allow continued proliferation but partially inhibit differentiation. Analysis of the molecular basis for the decrease in IgM production shows that the increased transcription of the Ig-H chain gene induced by LPS is abrogated by staurosporine treatment whereas alteration of 3' end processing is not affected. These experiments indicate that LPS continues to mediate its effect on some of the more distal differentiative events through protein kinase C even after initial cell activation. PMID- 1588052 TI - Functional heterogeneity between NKR-P1bright/Lycopersicon esculentum lectin (L.E.)bright and NKR-P1bright/L.E.dim subpopulations of rat natural killer cells. AB - In this report, we present data on heterogeneity of rat NK cells utilizing a combination of antibody and lectin-binding characteristics. Among NKR-P1bright NK cells, two discrete populations characterized as Lycopersicon esculentum lectin (L.E.)bright (60 to 80%) and L.E.dim (20 to 40%) were identified by flow cytometry. Comparison of the morphology of sorted NKR-P1bright/L.E.bright and NKR P1bright/L.E.dim cells indicated that both were greater than 90% LGL. An analysis of the functional capabilities of the sub-populations indicated that NKR P1bright/L.E.bright NK cells were more efficient in lysis of YAC-1 target cells (1743 LU20/10(7) cells) than were NKR-P1bright/L.E.dim cells (504 LU20/10(7) cells). Conversely, NKR-P1bright/L.E.dim NK cells were much more efficient at lysis of antibody-sensitized erythrocytes (antibody-dependent cellular cytotoxicity (ADCC)) (1412 LU20/10(7) cells) than were NKR-P1bright/L.E.bright cells (165 LU20/10(7) cells). Lysis of antibody sensitized P815 target cells yielded similar results as NKR-P1bright/L.E.dim cells and NKR-P1bright/L.E.bright cells had 905 LU20/10(7) and 189 LU20/10(7), respectively. Additional experiments indicated that NKR-P1bright/L.E.bright NK cells had the capacity to trigger lytic activity via NKR-P1 whereas NKR-P1bright/L.E.dim NK cells did not. NKR P1bright/L.E.bright sorted cells had a greater capacity to form conjugates with YAC-1 target cells than did NKR-P1bright/L.E.dim sorted cells. Conversely, NKR P1bright/L.E.dim NK cells were demonstrated to form E-A rosettes whereas the NKR P1bright/L.E.bright NK cells were not. Additional experiments indicated that tomato lectin itself was not responsible for the differences in reverse ADCC activity or ADCC activity among the subsets. However, lysis of YAC-1 target cells was modulated to some degree by the lectin. These data indicate that NKR P1bright/L.E.bright and NKR-P1bright/L.E.dim subpopulations of rat NK cells have different capacities for: 1) triggering through NKR-P1; and 2) E-A rosette formation and lysis of antibody-sensitized target cells by ADCC. PMID- 1588053 TI - H-2K double transfectants of tumor cells as antimetastatic cellular vaccines in heterozygous recipients. Implications for the T cell repertoire. AB - In this study we demonstrate that antitumor CTL repertoire restricted to a single MHC class I allele is higher in homozygous than in heterozygous mice. Consequently, transfection of two parental H-2K genes, but not of a single H-2K gene into a highly metastatic H-2K-negative tumor clone, resulted in abrogation of metastatic properties in F1 recipients. Clones of the 3LL carcinoma, which are low H-2Kb expressors, are nonimmunogenic and highly metastatic. Transfection of H 2K genes converted cells of such clones to nonmetastatic in syngeneic homozygous mice. However, in semi-syngeneic heterozygous mice, single H-2K transfectants retained their metastatic phenotype. In such heterozygous mice, i.e., in (H-2d x H-2b)F1, or in (H-2k x H-2b)F1, transfection of the two parental H-2K genes was required for complete abolishment of the metastatic phenotypes. In fact, in these heterozygous animals, even the local growth (i.e., tumorigenicity) of the double H-2K transfectants was significantly suppressed. These observations are attributed to the difference between homozygous and heterozygous mice with regard to the T cell repertoire restricted to a single H-2K-tumor-associated antigen complex. The reduced tumorigenicity and the complete abrogation of the metastatic phenotype was a function of a high immunogenic competence of the double transfectants in F1 heterozygous mice, which was significantly higher than that of single transfectants, as measured by the induction of CTL and of their precursors. Immunization of F1 mice by inactivated double transfectants conferred protection against metastasis formation by a subsequent graft of the parental D122 cells. Single transfectants were only marginally effective in conferring such protection. Applying an immunotherapy protocol, we observed that a series of vaccinations with double transfectants of animals already carrying a parental tumor reduced significantly the generation of metastasis by the otherwise highly metastatic D122 cells. PMID- 1588054 TI - Open tibial fractures: current orthopaedic management. AB - Treating the spectrum of bone and soft-tissue injuries that can accompany open fractures of the tibia requires experience and judgment. It appears that the non reamed interlocking nail can safely and reproducibly stabilize most low-energy and selected high-energy open fractures of the leg. Severe open tibial fractures require a staged reconstructive protocol using external fixation as the method of bony stabilization. Differentiation between the requirements of individual injuries remains the key to successful treatment. PMID- 1588055 TI - Local response to biomaterials: bone loss in cementless femoral stems. AB - While cementless, porous-coated prosthetic components have shown a high percentage of satisfactory clinical results in short and intermediate term follow up, there are biologic problems associated with implantation of cementless devices that may predispose to clinical failure at longer term follow-up. Central to the issue of long-term performance is the problem of bone loss secondary either to adaptive bone remodeling processes or to the phenomenon of focal osteolysis. The stiffness of the femoral stem and the relative biologic inertness of the materials used are two properties of critical importance. In the future, continuing developments in the areas of prosthetic design, enhancement of fixation, biocompatibility, and biomaterials research will seek to address and resolve these problems. PMID- 1588056 TI - Advances in biomaterials and factors affecting implant fixation. PMID- 1588057 TI - Fractures of the distal radius. PMID- 1588058 TI - Current biomaterial problems in implants. PMID- 1588059 TI - Osteotomies of the hip in the prevention and treatment of osteoarthritis. AB - Osteoarthritis of the hip is common in our society, even in the relatively young patient. Most of this osteoarthritis is mechanical in etiology and is secondary to residual deformity from developmental hip disease. This type of osteoarthritis can often be predicted and prevented if the causative excessive joint pressures are reduced in a timely fashion by corrective osteotomy. Realigning pelvic or intertrochanteric osteotomy of this preventive type is termed reconstructive; those osteotomies performed after osteoarthritis is established are termed salvage. Corrective osteotomy will be clinically successful only if the mechanical etiology for the potential or established osteoarthritis is clear and if the osteotomy succeeds in reducing the pathologically excessive joint loads. The clinical success of osteotomy also requires precise technical planning preoperatively and careful operative technique. PMID- 1588060 TI - Posterior screw plate fixation in thoracolumbar injuries. PMID- 1588061 TI - Pathophysiology of spinal stenosis. PMID- 1588062 TI - Epidemiology of spinal stenosis. AB - Although spinal stenosis has been recognized for nearly 190 years, no exact definition has yet been agreed on, a fact that has made incidence and prevalence studies all but impossible to interpret. The age at onset clearly correlates with the underlying pathomechanics. The disease appears to affect more men than women, except for degenerative spondylolisthesis, which affects more women. Occupation and somatotype do not appear to correlate with the development of symptomatic spinal stenosis. Although they are statistically more likely to have a smaller canal diameter, the black population does not seem to have a high incidence of symptomatic stenosis. Finally, although many syndromes have been reported to be associated with the development of spinal stenosis, the concomitant presence of degenerative changes appears to be a prerequisite to the development of symptomatic spinal stenosis. PMID- 1588063 TI - Biomechanics of lumbar disk disease. PMID- 1588064 TI - The radiologic evaluation of lumbar degenerative disk disease and spinal stenosis in patients with back or radicular symptoms. PMID- 1588065 TI - Osteoporosis and fusion. PMID- 1588066 TI - Wrist biomechanics. PMID- 1588067 TI - Adult scoliosis: evaluation and nonsurgical treatment. AB - Adult spine deformities may result from idiopathic and degenerative etiologies. These two entities may have superimposed on them an iatrogenic component from diskectomies or laminectomies done to relieve localized stenosis or disk herniations. The cumulative effect on the spine may result in painful and even crippling spine deformities. These are common, and their incidence in the adult population ranges from 3% to 30%, depending on the age group. Spine deformities are commonly painful and can be disabling, but they are rarely fatal. It is incumbent on the surgeon to understand the pathology involved in painful spine disorders and to have a reasonable understanding of the prognosis before attempting invasive therapy. An understanding of the risk/benefit ratio to the patient is also necessary. The decision to proceed with surgical treatment is justified in many cases, but it must be based on a thorough understanding of the anticipated benefits from surgical treatment and the risk of serious complications leading to multiple surgeries and results that can be less desirable than the original condition. PMID- 1588068 TI - Clinical applications for magnetic resonance imaging of the spine. PMID- 1588069 TI - Magnetic resonance imaging of acute spinal injury. PMID- 1588070 TI - Metastatic bone disease: general principles, pathophysiology, evaluation, and biopsy. PMID- 1588071 TI - Common surgical approaches to the shoulder. PMID- 1588072 TI - Differential diagnosis and surgical treatment of pathologic spine fractures. AB - The prognosis for survival has improved dramatically for cancer patients over the past three decades. Advances in systemic therapy have prolonged survival even in those who cannot be cured. The importance of managing spinal column disease and protecting the spinal cord has subsequently been amplified. Almost any patient presenting with detectable neurologic function and enough physical reserve to withstand an operation will benefit from a spinal stabilization, pain relief, and neural decompression; there are few exceptions. Advances in surgical technique and biomaterials have not only improved survival and functional outcome, they have diminished many of the postoperative complications that plagued earlier treatment techniques. Methods of preventing or correcting iatrogenic deformity have improved outcome. Newer fixation techniques promise to eliminate many of the causes of hardware and fixation failure previously seen. Improved medical management, antibiotics, and preoperative planning, along with techniques of preoperative embolization and early postoperative mobilization have made surgical management much less risky. Vertebrectomy, considered a last alternative in the past, is now coming to be seen as the conservative approach to tumor management in many situations. Appropriate surgical treatment can have a dramatic impact on function and outcome in patients with tumors of the spinal column, and should never be dismissed as an option without serious consideration. Advances in fixation systems, local and systemic therapy, and in our understanding of the biology of cancer promise even greater improvements for the future. PMID- 1588073 TI - Metastatic bone disease of the pelvis and femur. AB - Metastatic bone disease involving the pelvis and femur is a common clinical occurrence. A pathologic fracture in this region is a catastrophic event that results in significant pain and loss of function. Recent advances in surgical management of pathologic fractures, resulting in secure fracture stability or stable joint replacement, have allowed these patients to resume their pre fracture level of activity and ambulation. The surgeon must be familiar with the various devices available, because the choice of surgical procedure depends on the location of the tumor. In selected patients with extensive destruction, methylmethacrylate can be used to enhance the security of fixation and stability. Moreover, a more aggressive approach to prophylactic fixation before a catastrophic fracture develops has distinct advantages. PMID- 1588074 TI - Metastatic lesions of the humerus and the upper extremity. PMID- 1588075 TI - Carpal instability: treatment of ligament injuries of the wrist. PMID- 1588076 TI - General features of fractures in children. PMID- 1588077 TI - Initial management of the multiply injured child: the ABC's. PMID- 1588078 TI - Injuries of the epiphyseal plate. PMID- 1588079 TI - Occult fractures. PMID- 1588080 TI - Fractures of the proximal humerus and shaft in children. PMID- 1588081 TI - Fractures and dislocations about the elbow in children. PMID- 1588082 TI - Percutaneous pinning of supracondylar fractures of the humerus. AB - Percutaneous pinning following closed reduction of supracondylar fractures is a preferred technique for management of type III injuries. If there is no pulse, rapid closed reduction with percutaneous fixation should be done. No arteriogram is indicated before treatment. Nerve damage is not a contraindication to this procedure but should be documented prior to surgery. The duration of immobilization is three to four weeks, with pins left protruding through the skin, to be removed in the office. Complications of vascular insufficiency and cubitus varus can be avoided with this technique. PMID- 1588083 TI - Forearm fractures. PMID- 1588084 TI - Fractures and dislocations of the hip. PMID- 1588085 TI - Femur fractures in children. PMID- 1588086 TI - Pathogenesis of progressive valgus deformity following fractures of the proximal metaphyseal region of the tibia in young children. PMID- 1588088 TI - Current trends in the treatment of simple and complex bone deformities using the Ilizarov method. PMID- 1588087 TI - Serious fractures and joint injuries involving the foot and ankle. PMID- 1588089 TI - Management of fibular hemimelia using the Ilizarov method. PMID- 1588090 TI - Symes amputation for fibular hemimelia: a second look in the Ilizarov era. PMID- 1588091 TI - Epiphysiodesis for management of lower limb deformities. PMID- 1588092 TI - Surgical technique of physeal bar resection. PMID- 1588093 TI - Kienbock's disease. PMID- 1588094 TI - Third world orthopaedics. PMID- 1588095 TI - Cultural differences: North and South. PMID- 1588096 TI - Appropriate surgery and appliances for patients with deformities and paralysis in developing countries. PMID- 1588097 TI - Management of common Third World orthopaedic problems: paralytic poliomyelitis, tuberculosis of bones and joints, Hansen's disease (leprosy), and chronic osteomyelitis. PMID- 1588098 TI - Making orthopaedic education interactive, problem oriented, and on target. PMID- 1588099 TI - What we have learned from the wars. PMID- 1588100 TI - The history of the American Academy of Orthopaedic Surgeons. PMID- 1588101 TI - Assessing your office. PMID- 1588102 TI - Why computerize? PMID- 1588103 TI - Making it work. PMID- 1588104 TI - Choosing a computer system. AB - If you can set aside the intense marketing and the appealing gadgetry that surround computer systems, you will still be left with a complex and challenging set of choices. Investigate the hardware and software carefully, certainly, but pay especially close attention to the quality of the people involved, from the consultants to the vendors. Be as skeptical and cautious as any good customer, and make your decisions as though the future of your practice depended on it. PMID- 1588105 TI - Database technology for medical records. AB - Paper truncation may be the first goal that comes to mind when people think of computerized medical records, but this is probably the least realistic goal at present. Structuring a medical records system to improve record quality and to open the door to data analysis are two more realistic goals. Of the many significant barriers to computerized medical records, the most serious is the lack of agreement in the medical community regarding what should go into a medical record. Even small steps in that area should bring major improvements in available medical records software. Choosing a database for medical records requires familiarity with database principles and a detailed understanding of data needs. The safe choice is an SQL-based relational database, but a smaller system will suffice if present and future medical records challenges are small enough. The rate of change in the computer world is increasing all the time. Emerging and maturing technologies that can have a significant impact on medical records software include data entry tools such as the mouse, pen, and voice; better data retrieval tools such as GUIs and 4GLs; and software tools that use rules, pattern-matching, hypermedia links, and fuzzy logic to create systems that seem to think like humans. While computerized medical records systems are not yet comparable with medical office management systems, they should be someday. In the meantime, smart physicians will begin exploring possibilities on their own in order to reap some benefits at an early stage and to be better prepared when the tide finally turns. PMID- 1588106 TI - Computerized medical records. PMID- 1588108 TI - Unicompartmental arthritis: biomechanics and treatment alternatives. PMID- 1588107 TI - Patellofemoral pain. PMID- 1588109 TI - Distal femoral osteotomy for lateral gonarthrosis. PMID- 1588110 TI - Tibial osteotomy for varus gonarthrosis: indication, planning, and operative technique. PMID- 1588111 TI - Unicompartmental knee arthroplasty. PMID- 1588112 TI - New generation oral contraceptives of nineties. PMID- 1588113 TI - Reservations in medical education and jobs. PMID- 1588114 TI - Reproductive performance following Shirodkar's abdominal sling operation. AB - Over a period of 4 years from January 1986 to December 1989, 79 cases in whom Shirodkar's abdominal sling operation carried out, were studied. All the patients were admitted either in active labour or as cases of abortions or for the treatment of infertility. The incidence of full term normal vaginal delivery in this study was 69.56% and the incidence of caesarean section was only 2.9%. There was one case of posterior wall rupture following previous Shirodkar's sling operation. The recurrence rate of prolapse was only 8.69%. PMID- 1588115 TI - Bacteriology of wound infection: evaluation by surface swab and quantitative full thickness wound biopsy culture. AB - A total of 171 cases of wounds of various aetiology were examined and screened bacteriologically for evidence of infection by surface swab culture and quantitative full thickness wound biopsy culture techniques. Staphylococcus pyogenes was the most frequently isolated (39.9%) single organism. Other organisms being Escherichia coli (26.1%), Pseudomonas aeruginosa (15.4%), klebsiella species (5.8%), Streptococcus pyogenes (4.9%), proteus species (4.8%) and coliform organism (3.1%). Collectively the Gram-negative organisms were the majority among the isolated organisms. As indicator of wound infection, surface swab culture was found to be reliable in 72% cases when correlated with wound biopsy culture. The latter technique was found to be more consistently valuable (in 95% cases) both for regular assessment of the wounds as well as to judge the response to treatment. PMID- 1588116 TI - Humoral immunity status in patients with complicated pregnancies. AB - Serum immunoglobulin levels of 136 females inclusive of 20 non-pregnant volunteers, 21 normal pregnant mothers and 95 cases with complicated pregnancies were studied by radial immunodiffusion technique. Compared to normal western values immunoglobulin M levels were higher in 132 out of total 136 cases, immunoglobulin G levels were higher in 65 out of 95 cases with complicated pregnancies the majority of which included cases of eclampsia (16 cases), pre eclamptic toxaemia (21 cases) and pre-eclamptic toxaemia with antepartum haemorrhage (11 cases) and immunoglobulin A levels were normal in all except 11 cases comprising normal pregnancy (1 case), eclampsia (3 cases), pre-eclamptic toxaemia (5 cases) and pregnancy with hypertension (2 cases). PMID- 1588117 TI - Surgical manifestations of ascariasis in childhood. AB - Amongst 50 patients with surgical complications of Ascaris lumbricoides 35 patients (70%) were treated conservatively and 15 patients (30%) required surgical intervention which included squeezing of worms to distal colon, resection and anastomosis of ileum, appendicectomy and peritoneal lavage. Intestinal perforation was observed in 3 cases. Two patients (4%) died because of postoperative complications. Those presenting with subacute intestinal obstruction had no mortality or morbidity. Although a large number of roundworms were seen in the jejunum, the obstruction was generally observed in the distal ileum. PMID- 1588118 TI - Toxicity and side-effects of combination chemohormonal therapy of advanced breast cancer. AB - Seventy-five female patients suffering from advanced breast cancer were treated with toilet mastectomy, radiotherapy and oophorectomy (if premenopausal) or tamoxifen therapy (if postmenopausal) as well as chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil and prednisone. The most common side-effects of combined chemohormonal therapy were gastro-intestinal (nausea, vomiting, rarely diarrhoea) in 43 patients (57.3%), followed by alopecia in 23 patients (30.6%), myelosuppression in 12 patients (16%), extravasation and thrombophlebitis in 7 patients (9.3%), and mucositis and oral erythema in 3 patients (4%). Side-effects of tamoxifen therapy such as vaginal discharge, bleeding, hot flushes were encountered in 10 patients (13.3%). Hypercalcaemia, tumour flare and hepatic, renal, cardiac, pulmonary and neurological toxicities were not encountered. Improvement of 10-30% in Karnofsky performance status was noted in responders while 20-30% deterioration was observed in non-responders. Combination therapy was mostly well tolerated, side-effects were few and toxicities were temporary and reversible. PMID- 1588119 TI - Cavernous malformation of the midbrain. PMID- 1588120 TI - Gonadotropin releasing hormone and its clinical applications. PMID- 1588121 TI - Haemolytic disease of the newborn: prevention and management. PMID- 1588123 TI - Diversity in cellular signaling for nerve growth factor and insulin: variations on a common theme. AB - Numerous similarities exist in the cellular signaling events observed for insulin and nerve growth factor. Because the two hormones share many functional properties, and exhibit similar effects on neurons, the possibility of common early signaling events has been explored. Many studies have focused on the important role of protein phosphorylation. Two distinct but related mechanisms are discussed that may mediate, in part, the ability of these two hormones to regulate the activities of protein kinases and phosphatases. PMID- 1588122 TI - Regulation of transin/stromelysin and VL30 gene expression by intracellular calcium. AB - Changes in intracellular Ca++ levels are observed as a second messenger in response to a number of cellular agonists, including epidermal growth factor, transforming growth factor beta 1, and endothelin-1. The role of elevated intracellular Ca++ in transducing the effects of these three agonists on gene expression has been studied using two target genes: transin/stromelysin-1 and the endogenous murine retrovirus VL30. Although the effects of EGF and TGF beta 1 on transin/stromelysin-1 mRNA expression appear to be independent of these agonists' effects on intracellular Ca++ levels, elevated Ca++ interacted synergistically with activators of pkC to induce transin expression, even though neither agent alone could induce transin/stromelysin-1 expression. In contrast, the integrated VL30 retrovirus could be induced by Ca++ ionophores alone, and induction of VL30 mRNA by other agonists was blocked if intracellular Ca++ levels were held below a threshold value of 165 nM with Ca++ chelators. Genetic analysis of the VL30 upstream regulatory region indicated that a triple-repeat element present in the VL30 long-terminal repeat could function as an inducible enhancer, but responsiveness to either EGF or pkC activation required the concomitant elevation of intracellular Ca++. Because EGF was capable of inducing expression even in pkC depleted cells, providing Ca++ levels were elevated, these results indicate that elevated intracellular Ca++ is capable of interacting synergistically with multiple signaling pathways to stimulate increased gene expression. PMID- 1588124 TI - LDL receptors in keratinocytes. AB - The presence of sufficient amounts of cholesterol in the epidermis is necessary for proper functioning of plasma membranes in the viable epidermal cell layers and also for the barrier quality of lipid intercellular bilayers of the stratum corneum. Cholesterol can be generated by local epidermal synthesis, or imported from the circulation as low-density lipoprotein (LDL), which is internalized by the cells by receptor-mediated endocytosis. Because of the complex structure of the skin, a model consisting of cultured human keratinocytes has been used to study in detail the regulation of epidermal sterologenesis in relation to keratinocyte differentiation. Experimental modulation of the differentiation of normal human keratinocytes has been achieved by varying extracellular calcium concentration or by comparison of a number of human squamous carcinoma cell lines and normal keratinocytes. These studies have clearly demonstrated a reciprocal correlation between the ability of cells to differentiate and LDL receptor activity. Regulation of LDL receptor expression has been found to occur at the DNA, mRNA, and protein levels, depending on the cell line studied. In normal but not malignant keratinocytes, the induction of keratinocyte differentiation was associated not only with a decrease of functional LDL receptors but also with changes in their cellular distribution. This conclusion is drawn from the observations that only in normal human keratinocytes, cultured at physiologic calcium concentrations, high levels of intracellular, cytoskeleton-associated receptors were found. Differentiation-related modulations of the LDL-receptor expression and of the cellular LDL-receptor distribution found in cultured keratinocytes were in agreement with observations made in the epidermis in situ. PMID- 1588125 TI - Familial dysbetalipoproteinemia: a genetically heterogenous disease caused by mutations of the ligand apolipoprotein E. AB - Apolipoprotein E is present on the surface of very-low-density lipoprotein (VLDL) and chylomicron-remnants and is essential for the receptor mediated endocytosis of these particles via hepatic receptors. Several types of mutations of the apoE can cause a deficiency in the clearance of these remnant particles. An accumulation of lipoprotein-remnant particles may occur and familial dysbetalipoproteinemia (FD) develops. Genotyping of the various apoE variants and relation of these mutations with their effect on the lipoprotein-remnant removal have provided more insight in the structure-relationship of apoE ligand-receptor interactions. It is postulated that the apoE2 (Arg158----Cys) mutation is just outside the binding domain and that its deficient binding can be stimulated by exogenous factors. This hypothesis can explain why apoE2/E2 homozygosity can only induce FD under certain circumstances. ApoE mutations that occur in the binding domain, e.g., apoE2 (Lys146----Gln) have a direct effect on the ligand-receptor binding and, in these individuals, FD is inherited in an autosomal dominant way. Finally, apoE3-Leiden has an arginine residue at 112 and has a repeat of seven extra amino acid residues just outside the binding domain. Because of this repeat, conformational changes of the binding domain can ensue. Due to the fact that in apo E3-Leiden the arginine residue is present at 112, apoE3 Leiden is predominantly present on chylomicron and VLDL remnants. In these persons FD is also inherited in an autosomal dominant way. PMID- 1588126 TI - Ultraviolet B-irradiated antigen-presenting cells display altered accessory signaling for T-cell activation: relevance to immune responses initiated in skin. AB - A principal mechanism by which ultraviolet (UV) B radiation exerts its selective and antigen-specific suppressive influence on immune responses is through its effects on the capacity of antigen-presenting cells (APC) in skin, primarily Langerhans cells (LC), to differentially activate T-cell subsets. Recent evidence has indicated that LC, following UVB radiation, lose the capacity to stimulate proliferation of CD4+ Th1, but not of Th2, clones. Additional work has shown this acquired unresponsiveness of Th1 cells to represent a long-lasting form of clonal anergy that results from a block in their ability to produce IL-2. Although not completely delineated, these defects appear to be the result of preserved delivery of the primary signal transduced by interaction of the MHC/antigen complex on APC with the T-cell receptor complex, in the absence of a viable second signal normally delivered by interaction of a co-stimulatory factor from APC with its appropriate ligand on the T cells. These findings support the notion that the outcome of certain immune responses depends greatly upon conditions that are brought to bear on APC and T cells during the time of antigen presentation. PMID- 1588127 TI - Causes and mechanism of autoimmune disease: cyclosporin A as a probe for the investigation. AB - Organ-specific autoimmune disease can be elicited in rodents by manipulating the thymus/T cells. For example, elimination of a particular T-cell subset causes organ-specific autoimmune diseases, such as thyroiditis and gastritis, in otherwise normal mice. Environmental agents can cause similar autoimmune diseases by affecting the thymus/T cells. Cyclosporin A (CsA), a potent immunosuppressive drug, is an example. When a particular strain of newborn mice are daily administered with CsA for a limited period, they spontaneously develop organ specific autoimmune disease, such as gastritis with anti-parietal cell autoantibodies, later in life. CsA abrogates the production of CD4+T cells and CD8+T cells in the thymus. Consequently, these T cells are substantially depleted from the peripheral lymphoid organs, especially when the drug is administered from the day of birth. The autoimmune disease is prevented when CsA-treated newborn mice are inoculated with splenic T cells from normal syngeneic adult mice. On the other hand, removal of the thymus immediately after neonatal CsA treatment produces autoimmune disease with a higher incidence and in a wider spectrum of organs, i.e., thyroiditis, sialoadenitis of the salivary gland, gastritis, insulitis of the endocrine pancreas, adrenalitis, oophoritis, or orchitis. Each autoimmune disease is accompanied by the development of circulating autoantibodies specific for the corresponding organ-specific antigens. These findings taken together indicate that CsA causes autoimmune disease not by affecting the target self-antigens, but by interfering with a thymus/T cell-dependent control mechanism on the production/expansion of pathogenic self-reactive T cells. Various other environmental insults (such as ionizing radiation or virus) can also cause similar autoimmune diseases, presumably by a similar mechanism. PMID- 1588128 TI - Mutations in the insulin receptor gene in patients with genetic syndromes of insulin resistance and acanthosis nigricans. AB - Mutations of the insulin receptor gene have been identified in patients with genetic syndromes of insulin resistance associated with acanthosis nigricans. These mutations impair insulin responses by reducing the number of insulin receptors on the surface of target cells, or by reducing the receptor's ability to bind insulin or to undergo insulin-stimulated autophosphorylation, an important step in insulin action. Studies of mutant receptors expressed in transfection systems have contributed to our understanding of the structure function relationships of the insulin receptor. PMID- 1588129 TI - Functional diversity of histamine and histamine receptors. AB - In order to analyze the mechanisms by which a single biogenic amine like histamine is capable of inducing a wide variety of both physiologic and pathologic functions in various tissues/cells, histamine responses were dissected in detail from a biochemical and pharmacologic point of view. Histamine is synthesized by multiple isozymes of histidine decarboxylase, and catabolized by either diamine oxidase or histamine-N-methyltransferase. Synthesized intracellular histamine may play a role in cell proliferation, whereas released histamine binds to at least three different histamine-specific receptors, then activates various intracellular components, such as Ca++, cAMP, protein kinase, and ion channels. These second messenger pathways interact differentially with each other in various tissues/cells. Moreover, histamine not only activates its own receptors, but also activates other related receptors such as the serotonin 1c receptor. Therefore, to understand the complex actions of histamine, new approaches should be established, in which multiple phenomena can be monitored simultaneously. PMID- 1588130 TI - Mechanism of androgen action in cultured dermal papilla cells derived from human hair follicles with varying responses to androgens in vivo. AB - Androgens are major regulators of human hair growth, but their effects vary: many follicles are stimulated by androgens, e.g., beard; some remain unaffected, e.g., eyelashes; whereas scalp follicles undergo regression and balding in genetically disposed individuals. Because the dermal papilla controls many aspects of the hair follicle, androgens may act via the dermal papilla, affecting the other follicular components indirectly. In this hypothesis androgens would alter dermal papilla cell production of regulatory substances, e.g., growth factors and/or extracellular matrix components. To test this theory the mechanism of androgen action has been compared in primary lines of dermal papilla cells cultured from androgen-dependent follicles and relatively androgen-independent non-balding scalp. Androgen receptor levels were assayed by saturation analysis (9-10 points; 0.05-10 nmol/l) using the synthetic androgen [3H]-mibolerone and specificity was confirmed by competition studies. Androgen metabolism was investigated both intracellularly and in the media after a 2-h incubation with 5 nM [3H] testosterone. Carrier and [14C] steroids were added to the extracts before separation by thin-layer chromatography; steroid identity was confirmed by recrystallization. Dermal papilla cells from androgen-dependent follicles contained higher levels of specific, high-affinity, low-capacity androgen receptors than non-balding scalp cells. Testosterone metabolism also varied with beard, public and scalp cells containing testosterone and androstenedione intracellularly, but only beard cells producing 5 alpha-dihydrotestosterone, in line with the scanty beard growth found in 5 alpha-reductase deficiency. Elsewhere we have shown that cultured dermal papilla cells produce extracellular matrix components and mitogenic factors. These results all concur with our original hypothesis and suggest that further studies of such cells may elucidate the paradoxical effects of androgens on human hair follicles. PMID- 1588131 TI - Purification of androgen receptors in human sebocytes and hair. AB - Human sebaceous glands (SG) and hair follicles (HF) are target structures in the skin for androgen action. They contain steroid enzymes, capable of transforming weak androgens into the target-tissue-active androgens testosterone (T) and dihydrotestosterone (DHT), which bind to the androgen receptor (AR) to regulate cellular transcription. The AR from HF and SG from human scalp tissue has been purified greater than 86,000 times by phenyl-sepharose, DEAE-sephacel, gel filtration chromatography, and ultrafiltration. Sucrose density gradient analysis and non-denaturing gradient polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE revealed two molecular species of AR, an active form called monomer, capable of binding DHT with great specificity (4S, m = 62,000 Da, Kd = 0.6 nM, Bmax 8260 fmol/micrograms protein), and the other, an inactive form of the monomer called tetramer (10.8S, m = 252,000 Da, Kd = 2.9 nM). The two species are interconvertible, and after purification each appeared as a single band on SDS-PAGE. The conversion of the monomer to the tetramer AR form is influenced by reduced and oxidized glutathione, and possibly by an endogenous disulfide converting factor (DCF). Furthermore, biochemical events in the androgenic signal transduction sequence were shown to be stimulated by androgens via the AR. These include the total nuclear AR content, chromatin binding of AR complexes, and stimulation of RNA polymerase II, thus influencing gene expression, which is important in understanding regulation of HF growth and SG proliferation. PMID- 1588132 TI - Molecular defects in the androgen receptor causing androgen resistance. AB - Patients with androgen resistance exhibit a spectrum of abnormalities of male sexual development ranging from 46,XY phenotypic women (complete testicular feminization) to undervirilized fertile men. The definition of the androgen receptor gene structure has permitted the identification of the defects causing androgen resistance in a number of patients. In some individuals androgen resistance is caused by large-scale structural alterations in the androgen receptor gene. In most patients, however, the androgen receptor mutation is the result of single nucleotide substitutions, which cause premature termination or amino acid replacement that result in the synthesis of defective androgen receptor proteins. These amino acid substitutions identify residues crucial to the normal function of the androgen receptor protein. PMID- 1588133 TI - Epidemiology, pathogenesis, and prevention of Haemophilus influenzae disease. Veldhoven, Netherlands, 24-28 September 1990. PMID- 1588134 TI - Interaction of Haemophilus influenzae with mucus, cilia, and respiratory epithelium. AB - One nontypeable laboratory strain and five nontypeable clinical isolates of Haemophilus influenzae from sputum were investigated. Bacteria replicated from 10(4) to 10(8) cfu/ml over 24 h in an organ culture of human respiratory mucosa with only the intact mucosal surface exposed. By transmission electron microscopy, bacteria were not seen in association with normal respiratory epithelium, even after incubation for 24 h. H. influenzae infection caused patchy and occasionally confluent damage to epithelium, and the bacteria associated only with structurally damaged cells. Scanning electron microscopy revealed increased mucus, and slowed ciliary beat frequency was measured by photometry. Fimbriation of H. influenzae increased buccal cell adherence but did not facilitate association with normal or damaged respiratory epithelium or increase epithelial damage, indicating that adhesins other than fimbriae are present. Interactions with mucus, cilia, and epithelium are likely to be important in the pathogenesis of H. influenzae respiratory infections. PMID- 1588135 TI - Iron acquisition in Haemophilus influenzae: receptors for human transferrin. AB - As an adaptation to the iron-limited environment of the host, Haemophilus influenzae has a transferrin receptor-mediated mechanism of iron acquisition such that it can acquire iron directly from human transferrin. The absence of detectable siderophore production and the presence of transferrin binding in a collection of type b and nontypeable H. influenzae strains indicate that the mechanism is widespread in this species. Growth and binding studies have consistently shown that the receptor is specific for human transferrin, which correlates with the host range of this pathogen. Inhibitor experiments indicate that iron regulation of receptor activity is mediated at the gene level. Affinity isolation experiments indicate that, as observed with other bacterial pathogens, the receptor is composed of two iron-repressible outer membrane proteins, transferrin binding proteins 1 and 2. PMID- 1588136 TI - Targets of the beta-lactam antibiotics, penicillin-binding proteins, in ampicillin-resistant, non-beta-lactamase-producing Haemophilus influenzae. PMID- 1588137 TI - Pathogenic events during Haemophilus influenzae type b infection of human nasopharyngeal mucosa. PMID- 1588138 TI - Socioeconomic risk factors for invasive Haemophilus influenzae type b disease. AB - Socioeconomic risk factors for primary invasive Haemophilus influenzae type b (Hib) disease include factors that increase exposure to Hib (day care attendance, presence of siblings, and crowded households) and factors that increase an individual's susceptibility to Hib infections (short duration of breast feeding, parental smoking, and frequent infections in general). These factors are consistently found to be associated with risk of Hib disease in studies conducted in populations that differ in their Hib disease epidemiology. However, there are large differences in the prevalence of these risk factors among populations. According to present knowledge, variations in the prevalence of socioeconomic risk factors may explain most of the differences in the epidemiology of Hib disease and may also contribute to the differences in Hib vaccine efficacy in different populations. PMID- 1588139 TI - Cell surface changes in Haemophilus influenzae type b associated with a phenotypic increase in resistance to bactericidal antibody. PMID- 1588140 TI - Analysis of the attachment and invasion of human epithelial cells by Haemophilus influenzae biogroup aegyptius. PMID- 1588141 TI - Amplification status of capsule genes in Haemophilus influenzae type b clinical isolates. PMID- 1588142 TI - Interactions of Haemophilus influenzae with human endothelial cells in vitro. PMID- 1588144 TI - Pathophysiology of blood-brain barrier alterations during experimental Haemophilus influenzae meningitis. PMID- 1588143 TI - Haemocin production by encapsulated and nonencapsulated Haemophilus influenzae. PMID- 1588145 TI - The biology of Haemophilus influenzae type b vaccination failure. AB - Vaccination with unconjugated polysaccharide vaccine against Haemophilus influenzae type b (Hib) disease at a median age of 25 months was not effective in a group of children who developed Hib disease at a median age of 35 months. This group had normal serum immunoglobulin concentrations but impaired anticapsular antibody responses to Hib infection and to reimmunization with unconjugated polysaccharide. Another group vaccinated with conjugated polysaccharide vaccine at a median age of 18 months developed Hib disease at a median age of 24 months. Of this group, 40% had subnormal immunoglobulin concentrations, particularly IgG2, and showed impaired antibody responses to Hib infection, whereas those with normal immunoglobulin concentrations showed high antibody responses to Hib infection. In both vaccination failure groups, low antibody responders to infection responded to revaccination with Hib conjugate, and most children expressed the idiotype HibId-1 in convalescent or postrevaccination sera. The presence of this idiotype implies that vaccination failure did not result from an inability to use the V kappa II A2 variable region gene, which is used in the anticapsular antibody response of most healthy children. PMID- 1588146 TI - Evaluation of bacterial polysaccharide immune globulin for the treatment or prevention of Haemophilus influenzae type b and pneumococcal disease. AB - A human hyperimmune globulin termed bacterial polysaccharide immune globulin (BPIG) has been prepared from plasma donors immunized with Haemophilus influenzae type b (Hib), pneumococcal, and meningococcal vaccines. At a dose of 0.5 ml/kg, BPIG increased levels of antibody to Hib by greater than 0.15 microgram/ml within 4-6 h and by 2-4 micrograms/ml at 72 h. Thereafter, antibody declined, with a mean half-life of 27 days. BPIG treatment of Apache infants did not impair their active antibody responses to concurrently administered diphtheria-tetanus pertussis or Hib oligosaccharide-diptheria CRM197 conjugate vaccines. In high risk Apache infants, BPIG given at 2, 6, and 10 months of age provided significant protection from invasive Hib infection during infancy. Thus, BPIG may have utility in the prevention of Hib infections in high-risk patients who cannot be immunized adequately with Hib conjugate vaccines. PMID- 1588147 TI - Maternal immunization with the capsular polysaccharide vaccine for Haemophilus influenzae type b. AB - Maternal immunization with the capsular polysaccharide (PRP) vaccine of Haemophilus influenzae type b has been shown to extend the time that protective levels of maternal antibody are detected in infants. In a randomized, blinded trial, PRP or placebo was administered uneventfully to 213 women in the third trimester of pregnancy. Infants born to PRP recipients had significantly higher levels of antibody to PRP than did infants born to placebo recipients: 2.73 micrograms/ml compared with 0.33 microgram/ml. It was estimated that infants of mothers who received the PRP vaccine would be protected for an average of 4 months compared to an average of only 2 months for those of mothers who received placebo. Infants were followed for invasive H. influenzae type b disease through the first year of life; none was detected. PMID- 1588148 TI - Finnish efficacy trials with Haemophilus influenzae type b vaccines. AB - The first Finnish trial with Haemophilus influenzae type b vaccine was conducted during 1973-1974. It demonstrated that the polysaccharide vaccine was 90% efficacious in children greater than or equal to 18-24 months old. The immunologically superior polysaccharide-protein conjugate vaccines have been used since 1986 in randomized trials. The PRP-D vaccine (polysaccharide conjugated to diphtheria toxoid) was 90% efficacious when given at 3, 4, and 6 months of age to 58,000 infants. In 1988-1989, the PRP-D vaccine was compared with the HbOC vaccine (oligosaccharide conjugated to CRM197 protein). Follow-up is continuing, but both vaccines seem to be efficacious after two doses in infancy. PMID- 1588149 TI - Safety, immunogenicity, and efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b vaccine in a United States population: possible implications for optimal use. AB - Between February 1988 and June 1990, the safety, immunogenicity, and efficacy of Haemophilus influenzae type b (Hib) oligosaccharide conjugate (HbOC) vaccine was evaluated in a prelicensure trial of 61,080 children. HbOC was found to be safe and immunogenic in infancy. Extended follow-up revealed that as of 31 December 1990, 30 cases of invasive Hib disease had occurred in 74,699 children; 26 were in unvaccinated children and 4 in children who had received only one dose. No disease occurred in children who had received two or three doses. By 30 September 1991, another case had occurred in an unvaccinated child. Comparison of these efficacy data with those of Hib capsular polysaccharide-outer membrane protein conjugate vaccine (PRP-OMP) reveals that both were effective in preventing disease in the first year of life. However, the small cohort in the PRP-OMP study did not allow demonstration of duration of protection beyond 1 year. Ongoing surveillance in larger populations is necessary to allow comparison of the duration of immunity provided by these vaccines. PMID- 1588150 TI - Prevention of Haemophilus influenzae type b infections in Apache and Navajo children. AB - Prospective surveillance of Haemophilus influenzae type b (Hib) disease has been done since 1981 in two high-risk populations, White Mountain Apaches and Navajos. The attack rate in children less than 5 years of age is 5-10 times higher than in the general US population. Three vaccines were evaluated. Unconjugated Hib capsular polysaccharide produced lower antibody responses in 18- and 24-month-old Apache infants than in white infants. HbOC (Hib oligosaccharide covalently linked to the nontoxic mutant diphtheria toxin CRM197) produced low antibody responses in Navajo infants after one or two doses but induced responses similar to those in whites after three doses. The responses of 18-month-old Navajos to HbOC were lower than those of whites, but most achieved protective levels. PRP-OMP (Hib capsular polysaccharide linked to the outer membrane protein complex of Neisseria meningitidis) produced good immune responses in 2-month-old Navajo and Apache infants after a single dose. This vaccine was greater than 90% efficacious in protecting Navajo infants from Hib disease when given at 2 and 4 months of age. Even a single dose achieved a high protective efficacy. PMID- 1588151 TI - Preparation, antigenicity, and immunogenicity of synthetic ribosylribitol phosphate oligomer-protein conjugates and their potential use for vaccination against Haemophilus influenzae type b disease. AB - Synthetically prepared ribosylribitol phosphate dimer and trimer analogous to fragments of the capsular polysaccharide of Haemophilus influenzae type b, containing either an amino- or a (masked) thiol-functionalized spacer, were conjugated to protein by two different methods. The thiol-containing carbohydrates were conjugated to tetanus toxoid or H. influenzae outer membrane protein using N-succinimidyl 3-(2-pyridyldithio)propionate. Glutaric dialdehyde was used to conjugate the amino-containing carbohydrates with tetanus toxoid. All conjugates were able to bind antibodies raised against the native bacterial polysaccharide, as determined by competition ELISA. The glutaric dialdehyde conjugate prepared from ribosylribitol phosphate trimer and tetanus toxoid induced a strong polysaccharide-specific antibody response in mice and rabbits. PMID- 1588152 TI - Further approaches for optimizing polysaccharide-protein conjugate vaccines for prevention of invasive bacterial disease. AB - The design of conjugate vaccines to optimize their immunologic performance has not been studied extensively. Immunologic performance in relation to changing specific structural parameters in a conjugate can most effectively be analyzed using conjugate syntheses involving terminally activated polysaccharide fragments. Random activation of fragments before conjugation results in more complex and poorly defined conjugates. This is especially true when the length of polysaccharide fragments in polysaccharide-protein conjugates is varied. Both the antigenicity and immunogenicity of saccharide fragments are length-dependent, and antigenicity traditionally has been associated with oligosaccharide epitopes no larger than an antibody site. However, the recent identification of length stabilized conformational saccharide epitopes has added a new dimension to this concept. The immunologic performance of polysaccharide-protein conjugates is also length-dependent, probably requiring multiple epitopes for optimization. PMID- 1588153 TI - Brazilian purpuric fever identified in a new region of Brazil. The Brazilian Purpuric Fever Study Group. AB - Brazilian purpuric fever (BPF) is a life-threatening pediatric infection that is preceded by conjunctivitis and caused by Haemophilus influenzae biogroup aegyptius. BPF was first recognized during 1984 in the state of Sao Paulo. BPF was not reported in Brazil outside of Sao Paulo and the neighboring state of Parana until December 1989, when children with BPF were identified in the state of Mato Grosso. By April 1990, 10 children with confirmed BPF were identified from six widely separated cities in Mato Grosso. The overall attack rate for the combined population was 6/100,000 children less than 10 years of age. Six (60%) of the 10 children with BPF died. The recognition of BPF in Mato Grosso suggests that the H. influenzae biogroup aegyptius strain responsible for BPF has a wider geographic distribution than previously appreciated or may be capable of spreading. PMID- 1588154 TI - Effect of phosphate ester residues on the immunogenicity of CRM197-coupled Haemophilus influenzae type b capsular saccharides in 2-month-old infants. PMID- 1588155 TI - Interferon-gamma and interleukin-6 augment the human in vitro antibody response to the Haemophilus influenzae type b polysaccharide. PMID- 1588156 TI - High antibody responses to booster doses of either Haemophilus influenzae capsular polysaccharide or conjugate vaccine after primary immunization with conjugate vaccines. PMID- 1588157 TI - Humoral immune response patterns of human mucosae: induction and relation to bacterial respiratory tract infections. AB - Immunoglobulin-producing cells in mucosal tissues, quantitatively the body's most important humoral immune system, synthesize mainly dimers and larger polymers of IgA (poly-IgA) with incorporated J (joining) chain. Poly-IgA is actively transported to exocrine secretions by a transmembrane epithelial glycoprotein called secretory component. Enhancing secretory immunity by oral vaccination is an interesting possibility, but mucosal antigen uptake and local immune regulation are complex and only partly understood. Immunoglobulin isotype response patterns in the upper respiratory mucosa and distal gut are strikingly different. The preferential production of IgA1 in nasal and bronchial mucosae is intriguing in view of the frequent synthesis of IgA1-specific proteases by Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. A relationship of proneness to produce invasive disease and enzymatically induced deterioration of secretory immunity has been proposed. Differences in mucosal immune response patterns among patients with selective IgA deficiency or IgG subclass deficiencies also suggest that local humoral immunity is an important variable in resistance to infections. PMID- 1588158 TI - Epidemiology and prevention of respiratory tract infections due to nonencapsulated Haemophilus influenzae. AB - Nonencapsulated Haemophilus influenzae cause mainly respiratory tract infections, including otitis, sinusitis, and pneumonia. These infections may become chronic or recurrent in patients with bronchitis or otitis. Patients are usually infected with one strain at a time. During recurrent otitis, H. influenzae isolates have an outer membrane protein composition different from that seen during earlier episodes. In chronic bronchitis, H. influenzae strains persist for up to 1 year. In addition, isolates with different outer membrane protein compositions have been obtained that are antigenic variants of previous isolates. The variations occur in outer membrane protein b,c (P2), d (P5), or both. The variable parts are immunodominant, and antibodies to these parts are bactericidal. Cross-reactive bactericidal antibodies to outer membrane proteins have been elicited in immunized animals. These data indicate that natural immunity to nonencapsulated H. influenzae is mainly strain-specific but also that biologically active cross reactive antibodies can be elicited by immunization. PMID- 1588159 TI - Outer membrane proteins and lipopolysaccharides of nontypeable Haemophilus influenzae. AB - Several outer membrane proteins of nontypeable Haemophilus influenzae are potential vaccine candidates: P2 and P6 elicit antibodies that are bactericidal and protective in experimental models of infection. Other proteins are being investigated. A group of surface-exposed high-molecular-weight proteins that are major targets of antibody in human convalescent sera were identified. Monoclonal antibodies to the high-molecular-weight proteins of a prototype strain recognized two distinct but related proteins and were bactericidal for the prototype strain and other strains that shared the epitope recognized by the monoclonals. Genes encoding the two proteins in the prototype strain recognized by the monoclonals were cloned and sequenced. The sequences were distinct but related, and the derived amino acid sequences had sequence similarity to that of filamentous hemagglutinin of Bordetella pertussis, an important adherence factor and protective antigen. PMID- 1588160 TI - Animal models for the study of noninvasive Haemophilus influenzae disease: pulmonary clearance systems. AB - Nontypeable Haemophilus influenzae are increasingly being recognized as an important cause of disease in the lower respiratory tract. Information about the pathogenesis of these infections has been limited until recently by the paucity of experimental animal models for studying the host-parasite interaction in vivo. Three different animal models for investigation of the interaction of nontypeable H. influenzae with the lower respiratory tract have been used: Two involve the evaluation of short-term pulmonary clearance in mice or rats, while a new, long term infection model in rats mimics the more chronic bronchopulmonary infections sometimes caused by these organisms. Results obtained in these three model systems indicate that both humoral and cellular immune mechanisms are involved in immunity to lower respiratory tract disease due to nontypeable H. influenzae. PMID- 1588161 TI - Enzymatic, serologic, and genetic polymorphism of Haemophilus influenzae IgA1 proteases. PMID- 1588162 TI - Specific protection against acute bronchitis associated with nontypeable Haemophilus influenzae. PMID- 1588163 TI - Serum and middle ear antibody response in the chinchilla during otitis media with effusion induced by nonviable nontypeable Haemophilus influenzae. PMID- 1588164 TI - Epidemiology of invasive Haemophilus influenzae type b disease. AB - Invasive disease caused by Haemophilus influenzae type b (Hib) is typically a disease of young children, starting when the protection afforded by maternal antibodies is exhausted and ending when the child's own antibody production to the Hib capsular polysaccharide begins efficiently. There are, however, large variations between population groups in the incidence of the disease and the age at which it appears. Potential factors behind this variation include virulence genes of the bacteria and genetic susceptibility genes of the host. Although such genes and their effects can be identified, their impact on the disease's incidence is only minor. Potentially much more important appear to be socioeconomic factors that to a large extent determine the exposure of the child to Hib and to other infectious agents that may enhance both colonization and invasive infection by Hib. PMID- 1588165 TI - Epidemiology of acute respiratory tract infections, especially those due to Haemophilus influenzae, in Papua New Guinean children. AB - Acute lower respiratory tract infections (ALRI) are the most common cause of death in Papua New Guinean children. Haemophilus influenzae and Streptococcus pneumoniae are almost universally carried in the nasopharynx from a young age and commonly cause disease. While most H. influenzae isolates from blood and cerebrospinal fluid are serotype b, other serotypeable and nonserotypeable H. influenzae are more frequently isolated in Papua New Guinea than in developed countries. Low levels of antipneumococcal antibody, malnutrition, and upper respiratory carriage of invasive pneumococcal serotypes are associated with increased risk of ALRI. An oral H. influenzae vaccine given to adults with chronic bronchitis reduced the bacterial load in sputum and may thereby help reduce transmission of bacteria in the community. The efficacy of conjugate H. influenzae type b vaccine in preventing pneumonia must be determined in developing countries; vaccines against other types of H. influenzae will also be needed to control pneumonia and meningitis. PMID- 1588166 TI - Cloning and sequence analysis of a pilin-like gene from an otitis media isolate of nontypeable Haemophilus influenzae. PMID- 1588167 TI - The P6 outer membrane protein of nontypeable Haemophilus influenzae as a vaccine antigen. PMID- 1588168 TI - Serum antibody responses to nonencapsulated Haemophilus influenzae isolated from the nasopharynx of children with pneumonia. PMID- 1588169 TI - Epidemiology of acute lower respiratory tract infections, especially those due to Haemophilus influenzae type b, in The Gambia, west Africa. AB - Mortality surveys undertaken in rural areas of The Gambia, a small country on the west coast of Africa, indicate that acute lower respiratory tract infections (ALRI) are the most frequent cause of death among children and that approximately 1 in 25 rural Gambian children dies from an ALRI before the age of 5 years. Community surveys suggest that each child experiences an average of one episode of ALRI accompanied by radiographic changes before reaching this age. Etiologic studies have shown that pneumococci, Haemophilus influenzae type b (Hib), and respiratory syncytial virus are the most important causes of ALRI in Gambian children who present to a hospital, and the same three organisms are probably the major causes of severe ALRI in rural communities. Hib probably accounts for 5% 10% of cases of severe ALRI in Gambian children, and because the incidence of severe ALRI is high, an effective Hib conjugate vaccine might save as many childhood deaths by preventing pneumonia as by preventing meningitis. PMID- 1588170 TI - A prospective, population-based study of Haemophilus influenzae type b meningitis in The Gambia and the possible consequences. AB - A prospective population-based field study on Haemophilus influenzae type b (Hib) meningitis was carried out in The Gambia, West Africa. The annual incidence was 60 cases/100,000 children less than 5 years old and 297 cases/100,000 less than 1 year. The peak incidence was in those 5 months old, and 45% of cases occurred in those less than 6 months. The case fatality rate was 37%. Because the outcome did not appear to be affected by the logistics of receiving care, and resistance to chloramphenicol and ampicillin is not yet a problem, prevention of Hib disease at an early age seems the best solution. There are several options for vaccine trials. On the basis of available data, at least one of these trials seems warranted before Hib vaccination can be introduced in developing countries. Extrapolation of successful results in industrialized countries to a population of different genetic origin and living under different conditions seems questionable. PMID- 1588171 TI - Haemophilus influenzae type b infections in Victoria, Australia, 1985-1989. PMID- 1588172 TI - Invasive Haemophilus influenzae disease: a population-based evaluation of the role of capsular polysaccharide serotype. Haemophilus Influenzae Study Group. PMID- 1588173 TI - Serum C-reactive protein in the course of Haemophilus influenzae type b meningitis. PMID- 1588174 TI - Nasopharyngeal colonization during the first year of life. PMID- 1588175 TI - Incidence and clinical characteristics of invasive Haemophilus influenzae disease in adults. CDC Meningitis Surveillance Group. PMID- 1588176 TI - T cell regulation of the antibody response to bacterial polysaccharide antigens: an examination of some general characteristics and their implications. AB - The characteristics of thymus-derived (T) lymphocytes that regulate the magnitude of the antibody response to the capsular polysaccharide antigen of type III Streptococcus pneumoniae are considered within the context of a general homeostatic model for controlling the antibody response to microbial antigens of medical importance. Some experimental approaches are described in which the activities of such regulatory T cells are modulated to provide an increase in the development of host immunity, to improve the immunogenicity of poorly immunogenic antigens, or to eliminate the inhibitory effects of suppressor T cells. PMID- 1588177 TI - Thymus-independent and thymus-dependent responses to polysaccharide antigens. AB - Immune responses to polysaccharide antigens are thymus-independent (TI). Conversion of a polysaccharide antigen to a thymus-dependent (TD) antigen by covalent coupling to an immunogenic protein carrier alters the response to the polysaccharide in several important ways. Of primary importance for the prevention of invasive diseases in infants caused by encapsulated bacteria is the shift of the peak antibody response to a much younger age. Another important change is the development of memory B cells primed and ready to respond to either the polysaccharide, as would be encountered during an infection, or to a second dose of the same antigen. Additional immunoglobulin isotypes not seen or seen as a minor component in response to the polysaccharide are also a feature of the TD response. Finally, the diversity of the antibody population is increased after immunization with a TD vaccine compared with that seen after immunization with a TI vaccine. PMID- 1588178 TI - Immunoglobulin variable region gene expression in response to Haemophilus influenzae type b polysaccharide. AB - The mechanism(s) responsible for the ontogenic patterns of acquisition of the antibody repertoire is unknown. The immune response to Haemophilus influenzae type b (Hib) capsular polysaccharide provides an excellent model system in which to examine the ontogeny of immunoglobulin variable region expression. A panel of hybridomas secreting human antibodies specific for Hib capsular polysaccharide was developed using peripheral blood lymphocytes from donors immunized with Hib vaccines. Nucleotide sequence analysis of the heavy chain V regions expressed by four of these hybridomas suggests selective use of members of the VHIII gene family in combination with different D and J segments. The nucleotide sequences were highly homologous to two candidate germline gene sequences. Others have reported that these particular germline sequences are expressed in fetal liver, suggesting that the inability of young children to produce antibody to the Hib capsular polysaccharide is not due to failure to express these VH regions early in ontogeny. PMID- 1588179 TI - The role of complement in the host's defense against Haemophilus influenzae. AB - In vitro studies have shown that Haemophilus influenzae type b (Hib) can activate both the classical and alternative pathways of complement and generate complement dependent opsonic and bactericidal activities. In vivo studies and observations in complement-deficient patients have established the biologic significance of complement in the host's defense against H. influenzae. The complement system plays a significant role in the host's defense against Hib and against other encapsulated and unencapsulated H. influenzae, mainly by enhancing clearance from the bloodstream through its action as an opsonin in both nonimmune and immune hosts. Patients with genetically determined deficiencies of C3 or of the complement components involved in C3 activation have an increased susceptibility to H. influenzae. More recently, a relatively common deficiency of one isotype of C4 (C4B) has been shown to be associated with invasive Hib disease, suggesting that defects in complement-mediated host defense may be more common in systemic Hib infections than previously appreciated. PMID- 1588180 TI - G2m(23) immunoglobulin allotype and immunity to Haemophilus influenzae type b. AB - G2m(23), an allotype on IgG2 molecules, is detected in sera of about two of three Caucasians. Adults who are homozygous for G2m(23) have IgG2 antibody responses to types 14 and 18C pneumococcal polysaccharides fourfold higher than those of homozygous-negative subjects. Adults homozygous for G2m(23) also show higher IgG2 antibody responses to vaccination with Haemophilus influenzae type b (Hib) polysaccharide. Furthermore, adults heterozygous for G2m(23) show IgG2 antibody responses intermediate between responses of those homozygous-positive and homozygous-negative. In contrast, the magnitude of the IgG1 antibody responses of adults to Hib polysaccharide was similar irrespective of G2m(23) genotype status. The magnitude of the IgG antibody responses of children vaccinated with Hib polysaccharide is not affected by G2m(23) status, in part because the IgG subclass responses of children to this antigen are restricted to IgG1. Also, children show no consistent associations between G2m(23) allotype status and the risk of acquiring Hib disease or the risk of Hib vaccination failure. PMID- 1588181 TI - Invasive Haemophilus influenzae type b disease in children less than 5 years of age in Minnesota and in Dallas County, Texas, 1983-1984. AB - During 1983 and 1984, 733 cases of invasive Haemophilus influenzae type b disease in children less than 5 years of age were identified in Minnesota and in Dallas County, Texas. The overall incidence of disease was lower in Minnesota than in Dallas County. However, among urban residents, the rates of disease for whites were similar in the two areas. A higher rate of disease among whites in urban Minnesota compared with rural Minnesota resulted from an increased rate of cases for diagnoses other than meningitis. Local practices might have affected the rate of certain diagnoses, since ascertainment of Hib disease other than meningitis is more dependent on diagnostic practices than is diagnosis of meningitis. These data suggest that the incidence of invasive H. influenzae type b disease is influenced by the racial composition of the population, the rates of disease in specific subgroups, and possibly by local medical practices. Understanding the factors that contribute to the incidence of disease is necessary to interpret variations in different populations and changes over time. PMID- 1588183 TI - Cell biology of B lymphocyte activation by polysaccharides. PMID- 1588182 TI - Interactions of C3 and C4 with Haemophilus influenzae. PMID- 1588184 TI - The role of complement and murine monoclonal antibodies in binding and ingestion of Haemophilus influenzae type b by murine macrophages. PMID- 1588185 TI - A high-molecular-weight outer membrane protein that is a potential target for protective immunity to type b and untypeable Haemophilus influenzae. PMID- 1588186 TI - Molecular basis of invasive Haemophilus influenzae type b disease. AB - The molecular basis of central nervous system invasiveness by Haemophilus influenzae has been studied by using genetically defined mutants and in vivo and in vitro model systems. Capsular polysaccharide and lipopolysaccharide are important microbial determinants of the ability of H. influenzae to traverse the nasopharynx and localize in the cerebrospinal fluid and meninges after bacteremia. The genes for type b capsule confer greater invasive potential than do those for other capsular polysaccharides, although the molecular basis for this is not understood. Mutants have also indicated the role of lipopolysaccharide in enhancing the efficiency of bacterial translocation from the nose to the blood and in facilitating intravascular survival. Organisms that localize successfully in the blood and central nervous system are the progeny of a small fraction of the original challenge inoculum, often a single bacterium. PMID- 1588187 TI - Bacterial components and the pathophysiology of injury to the blood-brain barrier: does cell wall add to the effects of endotoxin in gram-negative meningitis? AB - In animal models, the lipopolysaccharide (LPS) from Haemophilus influenzae contributes to all the signs of meningitis associated with living bacteria. However, when tested in vitro, the amount of LPS in cerebrospinal fluid (CSF) in natural disease shows much greater effects on leukocytes than on endothelial permeability. To investigate whether other bacterial components act with LPS to incite meningeal inflammation, animals were challenged intracisternally with H. influenzae lysates. Upon neutralization of endotoxin, leukocytosis was greatly attenuated, but protein accumulation in CSF persisted. Cell wall from H. influenzae induced meningeal inflammation in a pattern opposite to that of LPS. Its ability to induce blood-brain barrier permeability greatly exceeded its ability to induce leukocytosis in vivo. Thus, cell wall, by acting on endothelia, and LPS, by inducing leukocytosis, may cooperate to induce inflammation in H. influenzae meningitis. Optimal reduction of inflammation and tissue damage in meningitis may require agents directed against cell wall as well as LPS. PMID- 1588188 TI - Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae. AB - Several chromosomal loci are involved in lipopolysaccharide (LPS) biosynthesis by Haemophilus influenzae. Two of these, lic1 and lic2, contain multiple open reading frames (ORFs) and include tandem repeats of the tetramer CAAT within and at the 5' end of the coding region of the first ORF in each locus. Variation in the number of repeats of CAAT is involved in the variable expression of LPS epitopes, and genes within these loci are involved in the biosynthesis of these epitopes. lic3 also contains multiple ORFs and the CAAT repeats in the same arrangement as in the other two lic loci. However, in lic3 metabolic functions are encoded by the downstream genes. ORF2 is galE, encoding uridine 5' diphosphogalactose 4-epimerase, and ORF4 is adk, encoding adenylate kinase. A mutant H. influenzae with a deleted galE gene had an altered LPS when grown on media lacking galactose and was of reduced virulence in infant rats. PMID- 1588189 TI - The Sauve-Kapandji procedure for chronic dislocation of the distal radio-ulnar joint with destruction of the articular surface. AB - The Sauve-Kapandji procedure has been performed in 15 non-rheumatoid patients with chronic distal radio-ulnar joint dislocation accompanied by joint damage or deformity. The clinical results were favourable; wrist pain improved in all patients, wrist flexion-extension was increased by more than 10 degrees in nine patients, grip strength of at least 80% of the contralateral wrist was achieved in 11 patients, and forearm rotation was more than 150 degrees in 12 patients. However, X-ray examination revealed an unstable proximal ulnar stump and radio ulnar convergence in all patients similar to that associated with the Darrach procedure. Although the Sauve-Kapandji procedure can preserve ulnar support of the wrist and is believed to yield more satisfactory results than the Darrach procedure, its extensive use is not recommended for non-rheumatoid distal radio ulnar joint disorders, but it is recommended for chronic distal radio-ulnar joint dislocation with articular injury or deformity. PMID- 1588190 TI - Excision of the pisiform in piso-triquetral osteoarthritis. AB - 12 patients with pain in the piso-triquetral region are described. 11 had radiological evidence of osteoarthritis of the piso-triquetral joint, which was confirmed in the nine cases treated by excision of the pisiform. Seven of these had complete relief of symptoms. The clinical findings are constant and relief of pain by conservative treatment is usually only temporary. Ulnar nerve symptoms were present in four patients and these were also relieved by surgery. Excision of the pisiform is a useful operation for this condition, which often remains undiagnosed due to incomplete clinical and radiological evaluation. Full return to normal function is the rule if the problem is not associated with other wrist pathology. PMID- 1588191 TI - The late reduction of carpal dislocations. AB - Five cases are reported in which open reduction of a lunate or peri-lunar dislocation was carried out after a delay of two weeks to six months. Results were poor in terms of range of movement and X-ray appearance, but function was surprisingly good, all patients returning to normal activities including heavy manual work. One patient later underwent excision of the radial styloid with an avascular scaphoid fragment; this apart, there were no requests for further surgical treatment. Open reduction remains a reasonable choice in the treatment of late presentation of lunate and perilunar dislocation. PMID- 1588192 TI - Combined radio-carpal and mid-carpal dislocation. A case report. AB - We describe a case of combined volar dislocation of the lunate and dorsal dislocation of the remainder of the carpus. Such a combination is probably very rare and the possible mechanism of injury is discussed. PMID- 1588193 TI - Intra-articular fractures at the base of the fifth metacarpal. A clinical and radiographical study of 64 cases. AB - The treatment of 64 intra-articular fractures at the base of the fifth metacarpal was studied. 11 fractures with minimal displacement had been immobilised in a plaster cast without reduction. The position was improved in five of 25 fractures treated by closed reduction and a plaster cast, six of nine fractures after percutaneous pinning, and 12 of 19 fractures after open reduction and internal fixation. At follow-up after a median of 4.3 years, 19 of 50 patients answering a questionnaire had intermittent pain, especially on firm grip. 43 patients were re examined clinically and radiographically: 21 (49%) had decreased grip power, and 28 had radiographical signs of osteoarthrosis. PMID- 1588194 TI - Locked metacarpo-phalangeal joint due to an intra-articular fracture of the metacarpal head. A case report. AB - A case of post-traumatic locked metacarpo-phalangeal joint is described. The locking was caused by an intra-articular fracture of the metacarpal head which was not diagnosed on the pre-operative radiographs. PMID- 1588195 TI - External fixation of unstable metacarpal and phalangeal fractures. AB - A prospective study of the management of 30 patients with 37 unstable or complex metacarpal or phalangeal fractures treated with the "Shearer" micro-external fixator was carried out over an 18-month period. The stability achieved, with minimal soft-tissue tethering, allowed early joint mobilisation with good or excellent function in 94% of metacarpal and 85% of phalangeal fractures by nine weeks. There were no cases of non-union and few complications. PMID- 1588196 TI - The chauffeur's fracture: simple or complex? AB - 14 chauffeur's-type fractures were treated by open reduction and internal fixation, mainly with Herbert screws. At average follow-up of 18 months, all had good or excellent functional results. The presence of an associated carpal injury in four cases indicates that the mechanism of injury may not be one of simple "backfire" and that a radial styloid fracture may represent the first stage of a more complex pattern. PMID- 1588197 TI - The range of motion of the metacarpo-phalangeal joint of the thumb and its relationship to injury. AB - A wide variation in the range of flexion of the metacarpo-phalangeal joint of the thumb in normal individuals is described. Patients with a poor range of flexion at this joint have a significantly higher incidence of indirect soft-tissue injury to the joint. PMID- 1588198 TI - Partial flexor tendon injuries: to repair or not. AB - The correct management of partially divided flexor tendon injuries is still in dispute. This study compares the results of repair with non-repair in zone 2 injuries. We conclude that tendons divided by 60% or less in cross-sectional area should not be repaired. PMID- 1588199 TI - Contrast arthrography in thumb polydactyly with variable morphological patterns. AB - Contrast arthrography was performed in 20 patients with duplicated thumbs where the interphalangeal, metacarpophalangeal, and carpometacarpal joints were involved. Three groups were apparent, those with no joint alteration, those with joint involvement and separate articular impressions, and those with abnormal duplex joints. PMID- 1588200 TI - Free flaps in the reconstruction of hand and distal forearm injuries. AB - We report a series of 32 free flap reconstructions following acute hand and forearm trauma. The series consists of two dorsalis pedis flaps, four scapular flaps and 26 lateral arm flaps. One flap became infected and failed completely, and a partial necrosis occurred in another flap. The transfers covered large skin defects, exposed tendons, tendon grafts, bone, bone grafts, joints, nerves and nerve grafts. The donor site morbidity was negligible. Our study shows that free microvascular flaps are a safe and convenient alternative to conventional flaps in hand surgery. The lateral arm flap seems very suitable for small and medium size defects. PMID- 1588201 TI - Complications and morbidity of the donor and recipient sites in 123 lateral arm flaps. AB - The lateral arm flap is a reliable and versatile free tissue transfer. However, the donor and recipient sites may produce an assortment of relatively minor complaints in a large proportion of patients. 109 (89%) out of 123 lateral arm flaps performed over a seven-year period were reviewed an average of three years after surgery. Unsatisfactory appearance of the donor site was noted by 27% of patients and was twice as likely to be reported by female patients and in cases in which the donor site was repaired by a split-thickness skin graft rather than by primary closure. Elbow pain was reported by 19%. Numbness in the forearm was reported by 59% and was unchanged during the follow-up period in the majority of patients. 17% of patients noted hypersensitivity of the donor site to a variety of stimuli such as cold or vibration. Hair formation was reported at the recipient site by 78% of patients. 83% of the patients found the flap to be bulky and 15% had undergone at least one procedure for debulking. We recommend that the use of the lateral arm flap should be limited to males and cases in which the resulting donor site can be closed primarily. PMID- 1588202 TI - Nail bed reconstruction with split-thickness nail bed grafts. AB - The results of reconstruction of chronic post-traumatic nail deformities are thought to be unpredictable. We have reviewed eight patients treated by split thickness nail bed grafts for deformities arising from defects in the sterile matrix. Appearance, adherence and function were improved in all cases, with no significant morbidity of the donor area. PMID- 1588203 TI - Quantifying interdigital web morphology. AB - A new method for the measurement of the interdigital webs of the hand is described and is shown to be reproducible. Measurements are taken from photographs and the method would be suitable for the comparison of post-operative appearances in the evaluation of "web creep" after surgery. PMID- 1588204 TI - Low cost cosmetic hand prostheses. AB - 66 patients with congenital or acquired amputations of the hand have been studied after fitting partial or complete silicone hand prostheses which can be manufactured at relatively low cost. Most patients used their prostheses on social occasions only and all but four expressed satisfaction with them. PMID- 1588205 TI - Provocative sensory testing in carpal tunnel syndrome. AB - This study reports the relationship between three clinical tests in the diagnosis of carpal tunnel syndrome and the stages of nerve compression. Assessments of 158 patients with carpal tunnel syndrome were reviewed retrospectively. 77% of patients had at least one of the clinical signs present. The incidence of positive pressure-provocative and Phalen's tests were similar and more likely to occur in combination than separately. Tinel's sign was more likely to be positive in the later stages of nerve compression. Our results suggest that the presence or absence of a provocative test is dependent upon the severity of the nerve compression. PMID- 1588206 TI - Thickening of the synovium of the digital flexor tendons: cause or consequence of the carpal tunnel syndrome? AB - Using a monofilament wire suture, the radial and ulnar edges of the flexor retinaculum were approximated in 14 white New Zealand rabbits. As a result, the volume of the carpal tunnel was diminished, and "carpal tunnel syndrome" was produced. At various intervals after this procedure the animals were sacrificed. The median nerve and all the digital flexor tendons passing through the carpal tunnel were excised "en bloc", and sent for histological examination. Vascular proliferation with perivascular round cell infiltration and oedema, and large areas of fibroblastic activity were observed around the digital flexor tendons. This was probably due to increased vascular permeability secondary to ischaemic endothelial damage. These findings are similar to those observed in the synovium of patients operated on for carpal tunnel syndrome. PMID- 1588207 TI - Transverse sliding of the median nerve beneath the flexor retinaculum. AB - Transverse sliding of the median nerve beneath the flexor retinaculum during active-resistant flexion of the fingers was sonographically demonstrated. Although it is a physiological phenomenon, it may cause mechanical nerve deformation in addition to longitudinal sliding when the nerve is subject to compression against the flexor retinaculum by tensed overlying flexor tendons. PMID- 1588208 TI - The incidence of gout in patients with Dupuytren's disease. AB - In a retrospective study we found that the incidence of gout in patients with Dupuytren's disease is 3.5%. The mean serum uric acid was 330 mumol/l. (5.5 mg./100 ml.) in men and 240 mumol./l. (4.0 mg./100 ml.) in women. The rate of hyperuricaemia was 7%. These are not significantly higher than the expected figures in Britain. PMID- 1588209 TI - Dupuytren's and epilepsy revisited. AB - The incidence of Dupuytren's disease amongst the residents of two epileptic centres was found to be 12.0% in one and 38.1% in the other. The overall incidence at the second was significantly higher than a control population (16.0%) and this difference was particularly apparent in patients over 50 years old. The distribution of the Dupuytren's disease was found to be very similar to that of non-epileptic patients. At both centres, the disease process was more severe, with an increased incidence of contractures. Drug therapy was not clearly implicated in the aetiology of this condition. PMID- 1588210 TI - Injury to the distal radius as a trigger to the onset of Dupuytren's disease. PMID- 1588211 TI - Soft tissue sarcoidosis of the hand: a case report. AB - A tumour of the hand may be the first manifestation of systemic sarcoidosis. In our patient, this mass involved only the soft tissues; more commonly, there is bone involvement as well. PMID- 1588212 TI - The sequelae of osteomyelitis of the proximal ulna occurring in early childhood. AB - Three patients presented with upper limb problems caused by the loss of the proximal ulnar shaft due to osteomyelitis which occurred in early childhood. The three patients had several features in common: instability of the elbow, dislocation of the radial head and shortness and bowing of the forearm, but hand and wrist function were largely unaffected. One patient had evidence of impaired function of the posterior interosseous nerve, presumably a traction injury. The treatment of these problems is discussed. In one patient, a child who had a functioning ulno-humeral joint, successful reconstruction of the ulna using a vascularised fibular graft was possible. PMID- 1588213 TI - Isolated tuberculosis of a skeletal muscle. AB - A case is described of tuberculosis in the muscle belly of abductor pollicis longus in a 25-year-old Asian woman. The complaint was of swelling and, as there was no evidence of tuberculosis elsewhere, the diagnosis was not made until the lump was explored surgically. PMID- 1588214 TI - Osteoid osteoma of the radial styloid mimicking stenosing tenosynovitis. A case report. AB - An osteoid osteoma of the styloid process of the radius mimicking de Quervain's tenovaginitis in a 28-year-old man is reported. As the clinical presentation and X-rays of the wrist were not typical of an osteoid osteoma, only the histological examination led to the correct diagnosis. PMID- 1588215 TI - Trigger digit: the needle or the knife? AB - We report our experience in conservative treatment of 30 patients with trigger digits followed up for an average of 22.3 months. In 26 patients (86.6%) the pain disappeared and the others experienced a remarkable improvement. Locking resolved in 23 patients (76.6%): in 19 patients immediately after the injection and in the other four gradually thereafter. Only three patients needed a second injection. All were satisfied and none required any other form of treatment. PMID- 1588216 TI - Stoma anxieties: a comparison of the attitudes of Asian migrants and the indigenous population in the United Kingdom towards abdominal surgery and the role of intestinal stomas. AB - We have studied stoma care nurses' experience with Asian patients having a stoma. The general public's attitudes to abdominal surgery in general were assessed in a survey of employees in Leicester. Many stoma care nurses are aware of the needs of Asian patients, especially with regards to ethnic dress, but only half of the ostomists who wanted to see a stoma care nurse or fellow ostomist were able to do so (chi 2 = 4.5, p less than 0.03). All ostomists considered counselling on education, employment and marriage inadequate. There is a high level of anxiety about stomas and these anxieties are surprisingly similar for all ethnic groups. PMID- 1588218 TI - The normal range and a simple diagram for recording whole gut transit time. AB - The time taken for radio-opaque markers to pass through the intestine has been measured in 25 healthy men, and 18 healthy women in both the follicular and luteal phases of the menstrual cycle. The subjects collected all stools after ingestion of the markers, the number of markers present in each stool was counted on a radiograph, and the number of markers retained in the body was thus determined for 12 hourly intervals after ingestion. The mean values (2 standard deviations) for men and women in both phases of the menstrual cycle proved to be so similar that the results have been combined to provide a single normal range. These data for the normal range for retained markers (as assessed by plain radiograph) are presented in diagrammatic form for clinical use. To assess whether a patient's whole gut transit time lies within the normal range a single type of marker can be used and an abdominal radiograph performed at 12 or 120 hours, the limits of the normal range. Normal subjects retain more than 20% of markers within 12 hours and less than 80% after 120 hours. If desired more information can be gained by giving different types of marker on successive days, so that several transit studies providing intermediate values can be obtained from a single abdominal radiograph at 120 hours. PMID- 1588217 TI - The prognosis of rectal carcinoid tumours. AB - Carcinoid tumours of the rectum are very rare, and they may present special therapeutic problems for the surgeon. Tumour size and muscle layer invasion are the two most important factors predicting their malignant potential. A series of 20 patients with carcinoid tumours of the rectum were reviewed. 16 tumours less than 2 cm in diameter had neither muscle layer invasion nor lymph node metastases, with the exception of one tumour. Four patients with tumours larger than 2 cm died from metastatic carcinoid. In order to plan operative management endoluminal ultrasound should be performed preoperatively. Rectal carcinoid tumours should be treated like carcinomas of the rectum if they are 2 cm or more in diameter or if they demonstrate muscularis propria invasion independent of tumour size. PMID- 1588219 TI - Can proctological procedures resolve perianal pruritus and mycosis? A prospective study of 23 cases. AB - Twenty-three patients with pruritus ani associated with anal mycosis underwent primary treatment of a concurrent anal disorder. The anal disorders included haemorrhoids (n = 9), fissure (n = 8), anal spasm without fissure (n = 5), and occult mucosal prolapse (n = 1). Pretreatment investigation of faeces for parasites was negative. The glucosal tolerance test and white blood cell count were normal in all cases. Culture of skin smears from the perianal region was positive for Candida only in 16 patients, Dermatophytes only in 6 and a combination of both in 1 patient. Following the appropriate proctological procedure, pruritus resolved or markedly improved in 20 patients. The remaining three patients required antifungal treatment with econazole. Two of these, however, continued to complain of pruritus. It is suggested that in patients with pruritus ani associated with perianal mycosis, antimycotic therapy should be used only if fungal infection persists after treatment of the underlying proctological disease. PMID- 1588220 TI - Experimental study of the efficacy of the endoluminal prosthesis in colonic anastomoses. AB - Colorectal surgery is still associated with a significant morbidity and mortality rate, mostly related to suture failure. We have carried out a randomized experimental study in dogs on colonic anastomoses exposed to a number of anastomotic risk situations. A total of 42 dogs was used. They were divided into three study groups (control, occlusion and diverticulitis), with and without an endoluminal tube. The aim was to assess the efficacy of the endoluminal prosthesis using clinical and radiological assessment of anastomotic healing. Pre and post-anastomotic intraluminal pressures were also measured to determine whether these might be a factor in suture failure. There were significant differences in suture failure in animals in which the endoluminal tube was used. Mean duration of placement was 10.5 days. In the colon healing study, no significant differences were found between the groups in the pathological examination or in the assay of hydroxyproline content. The presence of the endoluminal tube may increase the maximum pressure applied on the colon wall. No significant differences were found in the intracolonic pressure differentials between the different groups or after the inclusion of the endoluminal prosthesis. The results obtained establish the efficacy of the endoluminal prosthesis in protecting the colonic anastomosis, and could be a valuable technique in colonic anastomoses with a high risk of suture dehiscence. PMID- 1588221 TI - Anorectal lesions in human immunodeficiency virus-infected patients. AB - In a prospective study, we analysed the anorectal lesions observed in 148 human immunodeficiency virus-infected patients and compared the data with those reported in the literature. The majority of the patients (97.3%) were homosexual or bisexual men. The mean age of the population was 34.2 years. A history of previous sexually transmitted diseases was found in 79.7% of the male patients. The stage of HIV-related disease, according to the Centers for Disease Control classification, could be determined in 141 patients: 54.6% were stage II, 3.5% stage III and 41.8% stage IV. Anal condylomata were the most frequent manifestation, affecting 29.7% of the patients, 7.1% of whom showed moderate to severe dysplasia. The types were mainly 6, 11, 16 and 18, but types 31, 35 and 39 were also observed. Ulcerations were the most frequent non-condylomatous lesions, occurring in 41 patients; most (60%) were due to herpes viruses, and a large minority (21%) to cytomegalovirus. The etiology could not be determined in five cases. Anal sepsis was present in 11.4%, haemorrhoidal disease in 16.8% and fissures in 6%. Six patients developed Kaposi's sarcoma and seven, non-Hodgkin's lymphoma. No anal cancers were observed. Finally, wound healing was slowed in the patients operated on for haemorrhoids, fissures and suppuration. No statistical analysis could be performed because of the small number of patients. PMID- 1588222 TI - Double versus single stapling technique in rectal anastomosis. AB - A retrospective analysis to compare the single vs double stapled technique for rectal anastomosis was carried out on patients that underwent radical surgical resection between January 1986 and January 1989 at the Istituto Nazionale Tumori of Milan. In 143 patients anastomotic integrity had been checked both intraoperatively with air insufflation and postoperatively by water soluble contrast enema. A single stapled anastomosis (SST) was performed using the EEA instrument in 94 patients, and in 49 patients a double stapled (DST) using the EEA and TA instruments was performed. The level of the anastomosis was less than or equal to 10 cm from the anal margin in 94 patients (54 SST, 40 DST). In 52 patients it was greater than 10 cm (40 SST, 12 DST) (SST vs DST ns). The presence of anastomotic dehiscence occurred in 29 (20%) patients (17 SST, 12 DST). This was not related either to the anastomotic site or to the suture technique used. The dehiscence was located on the posterior wall in 79% of cases and in 58% the size was less than 1 cm. In 78% clinical symptoms were evident. There was no difference between SST and DST patients. Further surgery (colostomy) was necessary in six patients (2 SST, 4 DST). Two patients died through complications (1 SST, 1 DST); making an overall mortality rate of 1.0% and 2.0% in each group. There was no difference in infection rate and length of postoperative stay in the two groups. Our data demonstrate that both methods give similar results.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588223 TI - The value of age of onset and rectal emptying in predicting the outcome of colectomy for severe idiopathic constipation. AB - We have evaluated the predictive value of pelvic floor dysfunction (as characterized by abnormal contraction during defaecation straining or absent balloon expulsion) and evacuation proctography on symptomatic severe idiopathic constipation after colectomy with ileorectal or colorectal anastomoses for improvement and the use of laxatives. We also determined whether there was a relationship between the age of onset of symptoms and the symptomatic outcome after surgery. Forty-four women (mean age 34 years) were studied. Twenty patients had had a preoperative evacuation proctogram. Of these, 8 evacuated completely and 12 incompletely. Of the 29 patients in whom puborectalis electromyography was performed, 19 had paradoxal contraction on straining. There was no statistical relationship between symptomatic outcome and complete or incomplete evacuation on proctography, the presence or absence of puborectalis paradox or the age of onset of constipation (before or after the age of 10 years). Twenty-five patients had a preoperative balloon expulsion test. Of these, 14 were not able to expel a 50 ml water-filled balloon, and all 14 (100%) still experienced postoperative pain; 8 (57%) were still using laxatives. Of the 11 patients who were able to expel a balloon, 6 (55%) experienced pain and 1 (11%) still required laxatives postoperatively. The differences in postoperative pain and laxative requirements between those unable and those able to expel the balloon were statistically significant. Thus the balloon expulsion test may have predictive value when considering colectomy in patients with severe idiopathic constipation. PMID- 1588224 TI - Acute localized diverticulitis: optimum management requires accurate staging. AB - Between 1977 and 1989, 151 patients were treated in our institution for acute sigmoid diverticulitis. Thirty-one patients were operated on for diffuse peritonitis, and were excluded from the study. One hundred twenty patients had localized disease. There were 59 men and 61 women, with a mean age of 60 years (range, 30 to 87 years). Thirteen were under 40 years of age. A "phlegmonous" diverticulitis (no pericolic abscess) was diagnosed in 78 cases (group I). A pericolic abscess was identified in 42 cases (group II). The medical treatment was successful in 97% of the patients of the group I. Only 15 patients required a delayed elective resection for recurrence or chronic complications, within the next 24 months. There were no operative deaths. All the other patients were doing well after a mean follow-up of 5 years (9-144 months), without any disease related death. Patients presenting with a localized pericolic abscess (group II, n = 42) were initially treated either conservatively (n = 22) or by a more or less extensive drainage (n = 20). There were two deaths in the "conservative" group. Primary or delayed colonic resection was indicated in 34 cases because of uncontrolled sepsis, recurrence or secondary chronic complications. It is concluded that accurate classification of the disease is essential. If no peritonitis has developed, the presence of an abscess is the main determinant in both prognosis and treatment. Most patients who develop an acute phlegmonous diverticulitis do well with conservative treatment, and prophylactic resection is not indicated. Curative colectomy is reserved for patients developing persistent complications over the next few months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588225 TI - Rectal endosonography accurately predicts depth of penetration in rectal cancer. AB - Sixty-three patients with primary rectal adenocarcinomas have been examined prior to surgery with rectal endosonography (ES). Maximum depths of tumour penetration measured endosonographically have been compared with subsequent maximum depths measured on the fixed resected specimen (n = 30) and the histological slide (n = 61). In both cases there was a good degree of correlation between the ultrasonic estimations of depth and the histological ones (r = 0.36, p = 0.05, CI = 95% and r = 0.46, p less than 0.001, CI = 99% respectively). In 12 cases ultrasonic depths of tumour were also measured in the laboratory and then compared with depths from fixed (n = 12) and fresh specimens (n = 5) with a good correlation (r = 0.75, p = 0.005, CI = 99% and r = 0.79, p = 0.036, CI = 95% respectively). Rectal endosonographic estimation of rectal cancer depth of invasion is an accurate measure of tumour penetration and may help distinguish between fixation due to inflammatory tissue and tumour fixity. PMID- 1588226 TI - Innervation of internal anal sphincter--in vitro studies. PMID- 1588227 TI - Improvement of continence after abdominal rectopexy for rectal prolapse. AB - Twenty-seven patients with rectal prolapse and faecal incontinence were treated by abdominal rectopexy. They were studied clinically and by anal manometry both pre- and postoperatively. Postoperatively eleven patients gained full continence, eight had incontinence for flatus, six were incontinent for liquid stools and only two had daily soiling--none was totally incontinent. Those patients who gained continence had significantly higher maximal basal pressure (MBP) (p less than 0.05) postoperatively as compared to those who remained incontinent. There was an inverse correlation between MBP and grade of postoperative incontinence (p less than 0.02). The postoperative increase of MBP correlated (p less than 0.05) with improving incontinence score. Such changes did not occur with the maximal voluntary contraction pressure (MVCP). Our results suggest that functional recovery of the internal anal sphincter is better in postoperatively continent patients. PMID- 1588229 TI - [Cervico-cephalic hemangiomas and vascular malformations. Histopathological appearance and classification]. AB - We present the histological and clinicopathological classification of hemangiomas and vascular malformations, such as was produced by the work of the study group on hemangiomas and vascular malformations of Lariboisiere hospital. These lesions can first be classified according to the presence (phasic hemangioma of infants and pyogenic granuloma) or absence (malformations) of active cell proliferation. The malformations are classified according to their histological architecture and to the histological structure of the vessels they are composed of: capillary (hemangioma simplex, telangiectasias, etc.), capillary and/or venous (capillarovenous and cavernous malformations), arterial, venous and capillary (arteriovenous malformations). The classification of lymphatic malformations follows the same principles. The distinctive histological features of the various lesions are illustrated and briefly described. PMID- 1588228 TI - [Hemangiomas and superficial vascular malformations: classification]. AB - Superficial vascular malformations of the face, trunk and limbs are better known today, and they can be divided up into simple and complex vascular malformations. Simple vascular malformations may form five major categories: immature hemangiomas of infants, port-wine stains, capillarovenous angiodysplasias, and arteriovenous fistulae and malformations. Complex angiodysplasias are systematized (Sturge-Weber and Bonnet-Dechaume-Blanc syndromes, Cobb's metameric angiomatosis, Klippel-Trenaunay and Parkes Weber's syndromes) or disseminated (Weber-Osler-Rendu disease and blue rubber-bleb nevus syndrome). Various modalities of treatment may be contemplated, according to the type of malformations, and an interdisciplinary consultation is essential to decide whether a watch-and-wait policy, a physical method (laser), embolization, fibrosing injections, vascular, maxillofacial or plastic surgery, or a successive combination of various techniques should be resorted to. PMID- 1588230 TI - [Exploration strategy for superficial vascular malformations]. AB - Transillumination of cystic lymphangiomas, MRI of venous vascular malformations, pulsed Doppler and arteriography of arteriovenous malformations, echo-Doppler and radiomeasurement of malformations in the lower limbs are key examinations in the exploration strategy for superficial vascular malformations. PMID- 1588231 TI - [Management of hemangioma in the infant]. AB - Foster child hemangioma management depends on its usual spontaneously regressive evolution as it is a transient and benign vascular tumor like lesion. Most of the time clinical follow up is the only management. Investigations are indicated if treatment is needed (for decision and follow up) concerning only hemangiomas with a bad functional or esthetic prognosis (peri-orificial lesions and large locations of the face) or complicated hemangiomas with life-risk as sub glottic hemangioma, Kasabach and Merritt Syndrome, diffuse and liver hemangiomatosis possibly associated to cardiac failure. Basic treatment remains systemic corticosteroids with indications for early surgery or intralesional corticosteroids. PMID- 1588232 TI - [Indications for laser in the treatment of capillary hemangioma]. AB - Port-wine stains (PWS) are the only angiomas concerned with laser treatment. Before availability of tunable dye laser, Argon laser has to be consider as more efficient and safer than CO2 or yag lasers in that indication. As it is painful and not devoid of scarring effect in children it must be used after puberty. Nevertheless sport tests are necessary and have to be red after at least 2 to 6 months, as effect can be delayed to 1 year. Depending on PWS size and shape point by point technique or robotized scanning laser hand piece can be used. Criteria for good results are the followings: intensity of PWS colour, head and upper trunk location, lack of previous treatment, and irregular shape especially non homogeneous PWS with normal coloured skin areas. PMID- 1588233 TI - [Superficial and peripheral vascular malformations. Role of interventional radiology and of embolization]. AB - Embolization plays a major role in the management of arteriovenous malformations and fistulae on one hand, and of venous malformations and cystic lymphangiomas on the other hand. The treatment of arteriovenous fistulae today resorts to a primarily endovascular technique including the insertion under controlled flow of a releasable balloon or of a metallic coil positioned in the area of the fistula. Of course, this is possible only if there is a gap between the arterial and venous pathways. When the vessels are in direct contact, surgery must be preferred. In cases of arteriovenous malformations, embolization currently plays a great role; either it is performed with particles in the immediate preoperative period, two or three days before surgery, or as a definitive curative treatment with a polymerizing substance applied in situ. The use of flexible microcatheters allows penetrating into most of these vascular malformations and scattering polymerizing material all over the shunting areas. This is possible for superficial malformations, as is now performed, for instance, for brain AVMs. This embolization obviously can be contemplated only after a decision to treat these malformations has been made, knowing that they may be silent or acquire an uncontrollable evolution potential. This therefore is a collegial decision. As far as venous hemangiomas and cystic lymphangiomas are concerned, the greatest basic therapeutic means today is direct puncture and the in situ injection of a fibrosing substance under angiographic monitoring: the use of Ethibloc or, failing this, of absolute alcohol, has dramatically transformed the prognosis of these malformations, for which the surgical difficulties are well known (easy rupture, blood that often fails to coagulate, life-long progressive evolution).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588234 TI - [Venous vascular malformations and their treatment with Ethibloc]. AB - The use of Ethibloc must be contemplated as a first-intention treatment for venous malformations of the face. This sclerosing agent has transformed the functional, esthetic and psychological prognosis for these vascular malformations. PMID- 1588236 TI - [Vascular malformations of the limbs. Role of vascular and reconstructive surgery]. AB - The progress made by noninvasive exploration for the assessment of vascular malformations now allows the therapeutic strategies to be better established. While observation and conservative methods are most often chosen, some venous or arteriovenous malformations lead to contemplating a palliative or curative treatment. Two therapeutic choices may thus be used: embolization through an arterial route or, most often, through direct puncture of the malformation, or exeresis surgery, sometimes associated to surgery for tissue reconstruction. These techniques may be used alone, but are most often associated within the scope of a multidisciplinary management of the condition. PMID- 1588235 TI - [Cystic lymphatic malformations and their treatment]. AB - Lymphangiomas are remarkably well amenable to treatment with direct aspiration then embolization with a sclerosing agent derived from maize: Ethibloc. PMID- 1588237 TI - [Localized arteriovenous malformations of the limbs]. AB - The progress made by noninvasive explorations for the assessment of vascular malformations now enables us to better specify the therapeutic strategies. While a watch-and-wait policy and conservative methods remain the most frequent choice, some venous or arteriovenous malformations must lead to contemplating a palliative or curative therapy. Two therapeutic solutions may thus be used, either embolization through an arterial route or, most often, through direct puncture of the malformation, or exeresis surgery, which is sometimes associated aimed at surgery for tissue reconstruction. These techniques may be used alone, but they most often are associated within the scope of a multidisciplinary management of this condition. PMID- 1588238 TI - [Localized arteriovenous malformations of the limbs]. PMID- 1588239 TI - [Bone hemangioma of the limbs. A report of two cases in children]. AB - Hemangiomas of bone are rare lesions corresponding approximately to 1% of all primary bone tumors. Cases of hemangiomas in the vertebral bodies and in the skull occur fairly frequently but are unusual in other bones. The authors reported two cases of unusual and fairly rare aspects of this vascular tumor in children. In both cases, recurrences occurred and leaded to a wide bone resection in case one and to several curettage in case two. In these two case the histological type of hemangioma was the capillary one. In reviewing the literature we found no indication for wide resection of the benign forms in children. PMID- 1588240 TI - [Impact of angiodysplasia on bones]. AB - Vascular malformations usually have an impact on bones because of hemodynamic disturbances in the muscular and osteoperiosteal systems. In fact, even when these structures are not involved by arterial or venous malformations, the blood flow is altered in them. The consequences for bones affect the longitudinal growth of the skeleton of the malformed limb. Growth rarely becomes slower. On the contrary, the condition usually results in an acceleration of bone growth, which results in an excess in the length of the limb presenting with the vascular malformation. This overlengthening may be variably great, and the therapeutic indications must be adapted to its extent. When it is slight, compensation is sufficient to balance the pelvis. Conversely, when it is greater, its correction must be surgical. This surgery is aimed at equalizing the lower limbs, either by slowing down epiphyseal growth and shortening the longer side, or by progressively lengthening the other side, as the case may be. The respective indications of these methods must be carefully considered and adapted to each case, in order to obtain the best possible result with the smallest surgical risk. PMID- 1588241 TI - Molecular genetics, reductionism, and disease concepts in psychiatry. AB - The study of mental illness by the methods of molecular genetics is still in its infancy, but the use of genetic markers in psychiatry may potentially lead to a Virchowian revolution in the conception of mental illness. Genetic markers may define novel clusters of patients having diverse clinical presentations but sharing a common genetic and mechanistic basis. Such clusters may differ radically from the conventional classification schemes of psychiatric illness. However, the reduction of even relatively simple Mendelian phenomena to molecular genetics has been shown to be a surprisingly complex and problematic enterprise. Mental illnesses exist at many levels of including social, environmental, and developmental interactions. Reductionistic shifts in the classification of such a disease entity will have to address the interlevel dynamics that take place within the structure of theories of mental illness. The question of how molecular analysis of psychiatric disease will impact on the structure of existing theories and classification systems is the central topic of this paper. PMID- 1588242 TI - A sex caused inconsistency in DSM-III-R: the definition of mental disorder and the definition of paraphilias. AB - The DSM-III-R definition of mental disorder is inconsistent with the DSM-III-R definition of paraphilias. The former requires the suffering or increased risk of suffering some harm while the latter allows that deviance, by itself, is sufficient to classify a behavioral syndrome as a paraphilia. This inconsistency is particularly clear when examining the DSM-III-R account of a specific paraphilia, Transvestic Fetishism. The author defends the DSM-III-R definition of mental disorder and argues that the DSM-III-R definition of paraphilias should be changed. He recommends that the diagnostic criteria for specific paraphilias, particularly that for Transvestic Fetishism, be changed to make them consistent with the DSM-III-R definition of mental disorder. PMID- 1588243 TI - An analysis of interpersonal manipulation. AB - The term 'manipulation' is frequently employed but rarely discussed or defined in psychiatric circles. This paper reviews previous conceptual analyses of the term by philosophers and psychiatrists, and examines its use in ordinary discourse. A series of characteristics which comprise the conceptual core of the term when it is unambiguously applied in interpersonal settings are proposed. Manipulation is contrasted with other behavior control methods such as rational persuasion and coercion, with emphasis on the role played by deception and the communicative context in which the manipulative transaction occurs. It is argued that manipulative behavior is fundamentally intentional, and the usefulness of the concept of 'unconscious manipulation' is questioned. Though the proposal that Manipulative Personality Disorder be formally recognized as a new diagnostic category is rejected, it is urged that the concept of manipulation receive wider attention and discussion within the mental health community. PMID- 1588244 TI - Diagnosing blame: responsibility and the psychopath. AB - The diagnosis of psychopathy is controversial largely because of two notions: first, that because of their defects, psychopaths cannot understand morality, and second, that these defects should thus excuse psychopaths from moral responsibility for their actions. However, it is not clear just what is involved in understanding morality. The argument that the psychopath is ignorant of morality in the same way that one might be ignorant of facts is difficult to sustain. However, a closer examination of the psychopath's peculiar deficiencies reveals that the psychopath's understanding of mortality might be impaired in other ways. PMID- 1588245 TI - Is there androcentric bias in psychiatric diagnosis? AB - Flaws, biases, and ethical problems surrounding research and diagnosis may lead to inappropriate or inequitable treatments that exacerbate or fail to improve the misery that some individuals face due to their psychiatric conditions. Possible androcentric biases in the choice and definition of categories for diagnosis available in DSM-III-R may in turn influence the approaches of therapists to clients, particularly male therapists towards female clients. Androcentric bias in diagnosis, which may also be reflected in the values of the psychiatrist, may lead to treatment regimens designed to make clients fit into roles, positions, and norms prescribed by a culture reflecting patriarchal values. Some acceptance of attempts by feminists to correct androcentrism are beginning to emerge in psychiatric diagnosis. PMID- 1588246 TI - To be or not be a woman: anorexia nervosa, normative gender roles, and feminism. AB - This paper reviews the characteristics of anorexia nervosa described in the DSM III-R, relates them to normative gender roles and adolescent development, and critiques those roles on feminist grounds. Two apparently contradictory explanations for the irrational pursuit of thinness are considered: a) the anorexic thus attempts to conform to a socially defined feminine ideal; b) the anorexic thus attempts to avoid the appearance and consequences of mature womanhood. I propose that both explanations are applicable, together emplifying the ambiguity that Simone de Beauvoir considers characteristic of female experience. Because both explanations suggest a gender identity disorder, I question the fact that the DSM-III-R fails to indicate this linkage. I argue further that therapeutic considerations require efforts to alter the socialization factors that are implicative in anorexia nervosa. PMID- 1588247 TI - Psychiatric diagnoses: a continuing controversy. AB - Psychiatric Medicine has been accused justly of making its diagnoses on the patient's report of symptoms and the physician's subjective observations of the patient. The main problem has been the lack of reliable data compounded by the stigma of a mental diagnosis. More recently, third-party pressures have become an added threat to objectivity. New knowledge of brain function, especially neurotransmitters, and more specific and effective medication have made the need for accurate diagnoses more acute. Psychiatry has responded by frequent and often controversial changes in its diagnostic criteria. Much of the controversy stems from a lack of accurate measurements to validate the diagnoses, thereby allowing for differences of opinion of a highly subjective nature. The problem is complicated by the chronic, but irrational, belief that there is a separation between mental and somatic illness. PMID- 1588248 TI - The potentiating effect of prestretch on the contractile performance of rat gastrocnemius medialis muscle during subsequent shortening and isometric contractions. AB - The aim of the present study was to investigate the effect of an active stretch during the onset of a muscle contraction on subsequent active behaviour of the contractile machinery within an intact mammalian muscle-tendon complex. Muscle length and shortening velocity were studied because they may be important variables affecting this so-called prestretch effect. Seven gastrocnemius medialis (GM) muscles of the rat were examined. Tetanic, isovelocity shortening contractions from 3 mm above muscle optimum length (l0) to l0 - 2 mm, at velocities of 10-50 mm s-1 (dynamic experiments), were preceded by either an isometric contraction (PI) or an active stretch (PS). By imposing quick length decreases between the prephase and the concentric phase, all excess force generated in the prephase was instantaneously eliminated. This procedure only allowed small force changes during subsequent shortening (caused by the intrinsic properties of the contractile machinery). In this way, the influence of series elastic structures on subsequent muscle performance was minimized. Experiments were also performed at lengths ranging from l0 + 2.5 mm to l0 - 1.5 mm, keeping the length constant after the initial quick length changes (isometric experiments). For the dynamic experiments, enhancement of the performance of the contractile machinery (potentiation) was calculated as the ratio of the average force level over each millimetre of shortening during PS to that during PI conditions (PS/PI). For the isometric experiments, the PS/PI force ratio after 300 ms of stimulation was used. The main result of the present study confirmed results reported in the literature and experiments on isolated muscle fibres. For all conditions, a potentiation effect was found, ranging from about 2 to 16%. Muscle length appeared to have a large positive effect on the degree of potentiation. At the greatest lengths potentiation was largest, but at lengths below optimum a small effect was also found. A negative influence of shortening velocity was mainly present at increased muscle lengths (l0 + 2.5 mm and l0 + 1.5 mm). For the dynamic experiments, no interaction was found between the effects of muscle length and shortening velocity on potentiation. However, there was a clear difference between the isometric and dynamic responses: the dependence of potentiation on muscle length was significantly greater for the isometric contractions than for the dynamic ones. These isometric-dynamic differences indicate that the processes underlying prestretch effects operate differently under isometric and dynamic conditions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588249 TI - Heart rates and swim speeds of emperor penguins diving under sea ice. AB - Heart rate during overnight rest and while diving were recorded from five emperor penguins with a microprocessor-controlled submersible recorder. Heart rate, cardiac output and stroke volume were also measured in two resting emperor penguins using standard electrocardiography and thermodilution measurements. Swim velocities from eight birds were obtained with the submersible recorder. The resting average of the mean heart rates was 72 beats min-1. Diving heart rates were about 15% lower than resting rates. Cardiac outputs of 1.9-2.9 ml kg-1 s-1 and stroke volumes of 1.6-2.7 ml kg-1 were similar to values recorded from mammals of the same body mass. Swim velocities averaged 3 m s-1. The swim speeds and heart rates suggest that muscle O2 depletion must occur frequently: therefore, many dives require a significant energy contribution from anaerobic glycolysis. PMID- 1588250 TI - Metabolic rates of freely diving Weddell seals: correlations with oxygen stores, swim velocity and diving duration. AB - The metabolic rates of freely diving Weddell seals were measured using modern methods of on-line computer analysis coupled to oxygen consumption instrumentation. Oxygen consumption values were collected during sleep, resting periods while awake and during diving periods with the seals breathing at the surface of the water in an experimental sea-ice hole in Antarctica. Oxygen consumption during diving was not elevated over resting values but was statistically about 1.5 times greater than sleeping values. The metabolic rate of diving declined with increasing dive duration, but there was no significant difference between resting rates and rates in dives lasting up to 82 min. Swimming speed, measured with a microprocessor velocity recorder, was constant in each animal. Calculations of the aerobic dive limit of these seals were made from the oxygen consumption values and demonstrated that most dives were within this theoretical limit. The results indicate that the cost of diving is remarkably low in Weddell seals relative to other diving mammals and birds. PMID- 1588251 TI - Insect cardioactive peptides: regulation of hindgut activity by cardioacceleratory peptide 2 (CAP2) during wandering behaviour in Manduca sexta larvae. AB - The functional relationship between cardioacceleratory peptide 2 (CAP2) and hindgut activity during wandering behaviour was investigated in fifth-instar larvae of the tobacco hawkmoth Manduca sexta. Inspection of the alimentary canal on the day prior to wandering showed that the gut, in preparation for metamorphosis, was voided of all contents by 18:00 h. Associated with this event, which we refer to as 'gut emptying', was an increase in the frequency of hindgut contractions measured in vivo. No change in heart activity was seen during this developmental period. Measurements of the amount of CAP2 in the central nervous system (CNS) of fifth-instar caterpillars revealed that CAP2 storage levels declined sharply on the day of gut emptying. The drop in CNS levels of CAP2 at gut emptying was temporally correlated with the appearance of CAP2 in the haemolymph. CAP2, when applied at physiological concentrations to an in vitro larval hindgut bioassay, caused changes in several parameters, including contraction frequency and amplitude, and basal tension. In vivo administration of CAP2 elicited hindgut responses that were qualitatively and quantitatively similar to those seen in vitro. Developmental studies on changes in CAP2 responsiveness during the last larval instar demonstrated that the hindgut is maximally sensitive to CAP2 on the day of gut emptying. Direct evidence in support of a role for CAP2 in fifth-instar larvae was provided by experiments in which the increase in gut activity in vivo seen at gut emptying was significantly reduced by injections of an anti-CAP antibody. Based on data from cobalt backfills and anti-CAP immunohistochemical staining, we propose that CAP2 exerts its effect on the larval hindgut at wandering via a local release from CAP containing neurones in the terminal ganglion that project directly to the hindgut. PMID- 1588252 TI - Insect cardioactive peptides in Manduca sexta: a comparison of the biochemical and molecular characteristics of cardioactive peptides in larvae and adults. PMID- 1588253 TI - The sauna and the heart. PMID- 1588254 TI - AIDS-associated Kaposi's sarcoma and the mechanisms of interferon alpha's activity; a riddle within a puzzle. AB - As yet, the pathogenesis of Kaposi's sarcoma in the context of the acquired immunodeficiency syndrome (AIDS) is not completely understood; this is also true for the mechanisms of action of interferon-alpha against this tumour. The present review focuses on recent developments that may provide some further insight into these issues. These include the angiogenesis of the tumour and the possible role of growth factors, such as the HIV-transactivating (tat) gene product and interleukin-6, the possible meaning of immunomodulating activities of interferon alpha, such as the rise in the number of CD4+ cells and the increase in beta 2 microglobulin serum concentrations in patients whose tumours respond to treatment, and the observed association between interferon's antiretroviral activity and tumour responses. PMID- 1588255 TI - Angina pectoris patients with normal coronary angiograms but abnormal thallium perfusion scan exhibit low myocardial and skeletal muscle energy charge. AB - Seven patients with angina pectoris and 201-thallium scintigraphy indicative of myocardial perfusion defects, but with normal coronary angiograms, were investigated. Metabolic events were studied in biopsies from myocardium and skeletal muscle (m. quadriceps femoris). Profound metabolic derangement was evidenced by a distinctly lowered energy charge in myocardium (0.88 +/- 0.04 in controls vs. 0.48 +/- 0.09 in patients; P less than 0.001) and skeletal muscle (0.92 +/- 0.01 in controls vs. 0.70 +/- 0.09 in patients; P less than 0.01). Accordingly, low values were recorded for ATP in both types of muscle, where ATP was lower than (myocardium) or the same as (skeletal muscle) ADP. The concentration of myocardial lactate was 115 +/- 74 mumol g-1 dry weight and that of skeletal muscle lactate was 11 +/- 3 mumol g-1 dry weight, compared to normal myocardial lactate of 18 +/- 10 mumol g-1 dry weight and normal skeletal muscle lactate of 11 +/- 3 mumol g-1 dry weight. Unprecedentedly low energy charge levels in both cardiac and skeletal muscle biopsies suggest that a systemic metabolic disease is highly probable. An inverse ATP/ADP ratio found in our patients is indicative of an aetiology different from ischaemia, which would not produce this relationship. PMID- 1588256 TI - Alcohol and sauna bathing: effects on cardiac rhythm, blood pressure, and serum electrolyte and cortisol concentrations. AB - The effect of heavy drinking and sauna bathing on cardiac rhythm, blood pressure, and serum electrolyte and cortisol concentrations was studied in 10 healthy male volunteers. Sauna bathing induced a comparable, significant increase in heart rate with and without alcohol consumption. During sauna bathing without alcohol, systolic blood pressure remained at the baseline level, whereas sauna and alcohol together decreased systolic blood pressure markedly from 136 +/- 4 to 113 +/- 3 mmHg (P less than 0.01). Neither sauna alone, nor sauna combined with alcohol intake, increased the frequency of premature ventricular complexes. Serum potassium, calcium and cortisol concentrations changed slightly during sauna, but alcohol consumption did not contribute further to this. In conclusion, sauna bathing, even in combination with heavy drinking, does not appear to provoke cardiac arrhythmias in healthy young men. However, the risk of hypotension is increased when sauna bathing is combined with alcohol consumption. PMID- 1588257 TI - Prognosis in glomerulonephritis. III. A longitudinal analysis of changes in serum creatinine and proteinuria during the course of disease: effect of immunosuppressive treatment. Report from Copenhagen Study Group of Renal Diseases. AB - A total of 395 consecutive patients with biopsy-proven glomerulonephritis were followed up for 14 years. At the time of entry to the study the patients were classified as having one of nine states of kidney disease according to serum creatinine levels and proteinuria. The transitions of the patients between the nine states were analysed. The influence of 14 independent variables including treatment with cytostatic drugs and prednisolone was estimated by the Cox proportional hazard model. Treatment with immunosuppressive drugs had an influence that emerged within the first month and continued for the next 2 months. Subsequent treatment with cytostatic drugs in combination with prednisolone delayed further improvement. Treatment with prednisolone or cytostatic drugs as single therapy for up to 6 months increased the risk of improvement of the disease, and had no significant effect on deterioration. The beneficial effect of the treatment persisted after withdrawal of the immunosuppressive drugs. The analysis revealed only a slight influence of the histological character of the glomerular changes. Post-streptococcal glomerulonephritis carried an increased tendency for improvement. Arterial hypertension affected the process in several states of kidney disease. Heavy proteinuria increased the risk of increasing serum creatinine levels. PMID- 1588258 TI - Relationship between smoking and diet: the MONICA-France project. AB - The association between smoking habits and diet was examined in a sample of 1126 men, aged 45-64 years, from the general population living in the three French MONICA monitoring areas: Bas-Rhin (BR) (n = 346), Haute-Garonne (HG) (n = 400) and Urban Community of Lille (UCL) (n = 380). Diet was assessed by the 3-day record method. The energy and nutrient intakes were calculated for each of the 3 centres, using the same food composition tables. Alcohol consumption was higher among smokers (P less than 0.001). Taking into account alcohol consumption, age, body mass index, centre, educational level and family size, the analyses showed no difference in non-alcoholic energy intake, proteins, carbohydrates, and total fat. However, smokers had a lower intake of polyunsaturated fatty acids (P less than 0.05) and dietary fibre (P less than 0.01) than non-smokers. With regard to food items, smokers had a higher intake of sucrose (P less than 0.05) and a lower intake of vegetables (P less than 0.001), dairy products (P less than 0.05) and cheese (P less than 0.05). These results suggest that analyses in future epidemiological research regarding the role of diet in the aetiology of tobacco related diseases should consider this association of potential risk factors. PMID- 1588259 TI - Coronary heart disease, cancer and mortality in male middle-aged light smokers. AB - We examined the effect of light smoking in relation to incidence of coronary heart disease (CHD) in a general population sample consisting of 6879 men aged 47 55 years and free of previous myocardial infarction (MI) at baseline. After a follow-up of mean duration 11.8 years, 11.0% of men smoking 1-4 cigarettes daily (n = 228) had suffered a major CHD event, compared to 3.7% of non-smokers (n = 2049) [adjusted odds ratio 2.8 (1.7-4.7)]. No further increase in risk was observed in men who smoked more. There was an increasing risk of death from cancer with the number of cigarettes smoked per day. Mortality was increased in all categories of cigarette smokers, particularly among the very heavy smokers, who had a mortality risk of 22% compared to 6% among nonsmokers [adjusted odds ratio 4.4 (2.7-7.1)]. Data from an examination 4 years later considered only those men who stated that their smoking habits were identical on both occasions (n = 3981). Among these subjects the incidence of CHD after a mean period of 7.1 years was 10.6% in men smoking 1-4 cigarettes per day, compared to 2.6% in nonsmokers [adjusted O.R. 4.6 (2.1-10.1)]. No dose-response effect was observed. Even very light cigarette smoking considerably increases the risk of CHD in middle-aged men. PMID- 1588260 TI - Oral ketoconazole prophylaxis for Candida infections during induction therapy for acute leukaemia in adults: more bacteraemias. AB - We determined whether ketoconazole prophylaxis might reduce Candida colonization and infections in adult patients with acute leukaemia. During first-remission induction therapy 50 patients were treated with 200 mg ketoconazole administered orally daily, while 57 patients received placebo in a double-blind, randomized trial. The duration of severe neutropenia (granulocytes less than 0.1 x 10(9) l 1) represented 36% of the study period in the ketoconazole group and 26% in the placebo group (P = 0.043). Although fewer patients presented with positive Candida surveillance cultures and serological evidence of Candida infection in the ketoconazole group compared to the placebo group, two candidaemias and one Trichosporum fungaemia were observed in the ketoconazole group. Moreover, significantly more bacteraemias were noted in the ketoconazole group (n = 37) than in the placebo group (n = 21) (P = 0.004). Thus, although oral ketoconazole prophylaxis might be associated with less Candida colonization and fewer seroconversions, it also resulted in more bacteraemias and longer duration of severe neutropenia, suggesting that caution should be exercised when ketoconazole (or related drugs) is given to this group of immunocompromised hosts. PMID- 1588261 TI - Patients at risk for inappropriate antibiotic treatment of bacteraemia. AB - In order to define patients at high risk for inappropriate antibiotic treatment of bacteraemia, we compared 682 bacteraemic patients, treated with an antibiotic drug to which the infecting micro-organism was susceptible, with 419 patients who were inappropriately treated. On a multivariate logistic regression analysis including only clinical variables, four factors were found to be both significantly and independently associated with inappropriate antibiotic treatment: hospital-acquired bacteraemia (odds-ratio (OR) of 1.9), antibiotic treatment in the month prior to the bacteraemia (OR 1.9), residence in a nursing home (OR 1.8), and the presence of a central line (OR 1.7). A second model, including bacteriological data, showed four micro-organisms to be independently associated with inappropriate antibiotic treatment: Candida sp. (OR 14.2), Acinetobacter sp. (OR 5.0), Enterococcus sp. (OR 3.6) and Pseudomonas sp. (OR 2.2). In this model, only two clinical features were included: hospital-acquired infection and previous antibiotic treatment. Special efforts should be made to improve empirical antibiotic treatment in the groups defined above, and to facilitate early laboratory diagnosis of the micro-organisms associated with inappropriate treatment. PMID- 1588262 TI - Elements of informed consent in clinical research with drugs: a survey of Spanish clinical investigators. AB - An anonymous survey was conducted on 302 Spanish clinical investigators in order to determine whether a patient's information sheet should be prepared for each clinical trial, and what items of information should be included. The survey, using close-response type questions, included 23 proposed items of information. A total of 275 (91%) investigators considered it necessary that a patient's information sheet be prepared for each clinical trial. At least 83% of those investigators considered that seven items of information should always be included: an invitation to participate in a clinical trial, the aim of the study, a description of the predictable benefits and risks, a declaration that participation is voluntary, and a statement that refusal to participate does not imply loss of normal medical care and that the trial has been approved by a Clinical Trials Committee. Only 29% and 53% considered that the patient should always be informed about clinical trial design and data confidentiality, respectively. Overall, the responses obtained are in line with most of the elements of informed consent regarded as 'basic' in US regulations and included in the European Community and Nordic Good Clinical Practice guidelines. PMID- 1588263 TI - Secondary polycythaemia associated with nocturnal apnoea--a relationship not mediated by erythropoietin? AB - A polysomnographic study was undertaken in nine patients with unexplained polycythaemia and nine age- and sex-matched controls. Circulating plasma levels of immunoreactive erythropoietin (IrEPO) were analysed before and after sleep. Seven out of nine polycythaemia patients were found to have sleep-disordered breathing and fulfilled the criteria for the sleep apnoea syndrome. Erythrocyte volume fraction was by definition higher among polycythaemia patients, and showed a weak positive correlation with minimum oxygen saturation during sleep (P less than 0.05). However, plasma IrEPO did not differ between the two groups or between morning and evening samples within the respective groups. In a separate study, IrEPO was repeatedly analysed during sleep in a group of six patients with severe obstructive sleep apnoea and six matched controls. No correlation with severity of sleep-disordered breathing was found. None of these patients had polycythaemia, and there was no obvious diurnal variation in IrEPO levels. A nocturnal sleep study may be warranted in patients with unexplained polycythaemia. Obstructive sleep apnoea does not appear to be related to increased IrEPO levels, although polycythaemia has been reported as a relatively common finding in this disease. PMID- 1588264 TI - Frequency of low erythrocyte porphobilinogen deaminase activity in Finland. AB - The frequency of low erythrocyte porphobilinogen deaminase (PBGD) activity was investigated in 2234 blood donors and in 30 patients with acute intermittent porphyria. The mean enzyme activities (+/- SD) were 3.38 +/- 0.58 U and 1.82 +/- 0.41 U, respectively. Eighteen blood donors without any history of symptoms of porphyria or haematological disease had low PBGD activity (less than 2.20 U), and they were studied further. All of them also had subnormal concentrations of the erythrocyte enzyme protein, as determined by an immunological method. Lymphocyte PBGD activity was within the normal range, but this parameter does exhibit a wide overlap between normal and porphyric values. Urinary excretion of porphobilinogen was moderately increased in two of the blood donors. In four of the 18 families of the blood donors with low PBGD activity several first-degree relatives had low erythrocyte enzyme activity, consistent with a dominant mode of inheritance. The 5-aminolaevulinic acid loading-test was normal in the blood donors with familial occurrence of low erythrocyte PBGD. It is concluded that inherited defects in erythrocyte PBGD occurred among Finnish blood donors with a frequency of about 1 in 500. The defects may be identical with those in acute intermittent porphyria (AIP), but other mechanisms are also possible, e.g. a mutation in the erythroid specific part of the PBGD gene. PMID- 1588265 TI - Hyperglycaemic symptoms before diagnosis of non-insulin-dependent (type 2) diabetes mellitus in relation to 5-year outcome. AB - A group of newly diagnosed patients with non-insulin-dependent (type 2) diabetes mellitus (n = 133) were divided into two groups according to the symptoms of diabetes mellitus at diagnosis; a group (26 men and 17 women) with hyperglycaemic symptoms (polydipsia, polyuria, weight loss and tiredness) and a group (44 men and 46 women) without such symptoms. At the time of diagnosis, symptomatic patients tended to be leaner (P = NS), and they were more hyperglycaemic (P less than 0.001-0.06) and had lower insulin responses to an oral glucose load (P less than 0.01-0.05) than asymptomatic patients, but after 5 years no difference in these respects was found. No significant differences in the frequency of islet cell antibodies or cardiovascular diseases were found between the two diabetic groups. At the 5-year examination, the initially symptomatic patients were receiving pharmacological treatment for hyperglycaemia more often than asymptomatic patients. No consistent differences in clinical characteristics and 5-year outcome were observed between those diabetic patients who were diagnosed on the basis of hyperglycaemic symptoms and those who were diagnosed for other reasons. In conclusion, in middle-aged patients with newly diagnosed diabetes mellitus classified as non-insulin-dependent, diabetic symptoms at diagnosis did not predict the 5-year outcome of the patients in terms of metabolic control or cardiovascular events. PMID- 1588266 TI - Screening for antibodies against gliadin in patients with osteoporosis. AB - Intestinal disease might contribute to osteopenia. Measurements of IgA antibodies to gliadin have been established as an accepted screening procedure for detection of coeliac disease. When we applied these measurements to 92 patients with verified osteoporosis, 11 subjects (12%) were found to have elevated levels. This is markedly higher than the incidence in healthy subjects (3%). However, the patients with raised levels of IgA antibodies displayed no clinical symptoms and no laboratory evidence of calcium malabsorption. Thus their values for serum calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and osteocalcin, as well as the fasting urinary excretion of hydroxyproline and calcium, were similar to those found in other patients with osteoporosis. Intestinal biopsy verified coeliac disease in three patients and was normal in another three. This gives an incidence of verified coeliac disease in this patient group that is approximately tenfold higher than that in the healthy population. Subclinical coeliac disease appears to be unusually over-represented among patients with idiopathic osteoporosis, and screening for gliadin antibodies might therefore be a valuable addition to the routine assessment of the osteopenic patient. The mechanisms underlying the relationship are not clear, but calcium malabsorption is not evident. PMID- 1588267 TI - Interpretation of the electrocardiogram in suspected myocardial infarction: a randomized controlled study of the effect of a training programme to reduce interobserver variation. AB - We examined the effect of a training programme to reduce interobserver variation in interpretation of electrocardiography in suspected myocardial infarction. Sixteen doctors with 6-24 months of clinical training in internal medicine read serial electrocardiographic recordings in 107 patients and assessed whether signs indicative of acute myocardial infarction were present. There was disagreement in approximately 70% of cases. Eight of the doctors were randomly allocated to attend an 8-h intensive course on interpretation of electrocardiography in myocardial infarction. The remaining eight participants were allocated to a control group, received no training, and were not told about the subject of the study. All the doctors then reviewed another series of electrocardiographic recordings. No difference was found in the level of agreement within the two groups before and after the training programme, or between the two groups before and after the training. The raters' ability to discriminate between electrocardiograms with a high and low indication of infarction remained unaffected. We conclude that the training programme did not increase agreement regarding the interpretation of electrocardiographic data in suspected myocardial infarction. Our results suggest that the diagnostic approach of physicians is established at a very early stage in their clinical training. The effect of training programmes should be evaluated by the use of randomized clinical studies. PMID- 1588268 TI - Familial high-density-lipoprotein deficiency causing corneal opacities (fish eye disease) in a family of Dutch descent. AB - Fish eye disease (FED) is an extremely rare familial disorder characterized by severe HDL deficiency and extensive corneal opacities. This disorder appears to be a variant of familial lecithin: cholesterol acyltransferase (LCAT) deficiency in which the enzyme remains partly active yet the ability of the enzyme to esterify cholesterol in high-density lipoprotein (HDL) has been lost. The rarity of this disorder has limited advances in our understanding of the pathophysiology of the HDL deficiency. However, we here describe the clinical and biochemical presentation of a family with FED who are of Dutch descent. The proposition presented with HDL deficiency and corneal opacity. Subsequently, they were diagnosed as having FED by the absence of LCAT activity against a small proteoliposome substrate despite the presence of half-normal LCAT mass and a near normal ratio of unesterified to total cholesterol in plasma. Heterozygotes presented with half-normal LCAT activity, but not with decreased HDL. With the identification of this three-generation family, renewed investigation of this intriguing disorder of HDL is now possible. PMID- 1588269 TI - Effect of reduction of plasma triglycerides with gemfibrozil on high-density lipoprotein-cholesterol concentrations. AB - The aim of this study was to test the hypothesis that the plasma triglyceride (TG) concentration must be reduced below approximately 0.85-1.13 mmol l-1 (75-100 mg/dl-1) in order to achieve a substantial increase in plasma high-density lipoprotein-cholesterol (HDL-C) levels. The study design consisted of a non randomized clinical trial, which was conducted at an out-patient clinic at a university-affiliated VA Medical Center. The participants consisted of 55 ambulatory middle-aged men with a baseline fasting HDL-C concentration of less than or equal to 1.17 mmol l-1 (45 mg dl-1) and baseline TG in the range 1.13-5.6 mmol l-1 (100-500 mg dl-1). Subjects were treated with gemfibrozil, 600 mg twice a day for 3 months. Fasting plasma HDL-C, TG, low density lipoprotein cholesterol, and total cholesterol were measured at 1-month intervals for 3 months. Subjects were divided into three groups on the basis of TG level achieved on therapy: Group I (n = 14), TG less than 0.85 mmol l-1 (75 mg dl-1); Group II (n = 20), TG 0.86-1.41 mmol l-1 (76-125 mg dl-1); Group III (n = 21), TG greater than 1.41 mmol l-1 (125 mg dl-1). The mean increase in HDL-C in Group I was 0.20 mmol l-1 (7.8 mg dl-1), a significantly (P = 0.0067) greater increase than was observed in the other two groups. There was no correlation between the magnitude of change in TG and the magnitude of change in HDL-C concentration in the group as a whole (Pearson's correlation coefficient, r = -0.06, P = 0.6). In conclusion, the increase in HDL-C levels observed with gemfibrozil therapy is associated with the absolute level of TG achieved by therapy. Substantial increases in HDL-C concentration might not be expected to occur consistently unless TG levels are reduced to values that are considered below the usually cited 'normal' range. PMID- 1588270 TI - Plasma ionized calcium and cardiovascular risk factors in mild primary hyperparathyroidism: effects of long-term treatment with active vitamin D (alphacalcidol). AB - Primary hyperparathyroidism (HPT) has been associated with hypertension, hyperinsulinaemia, hypertriglyceridaemia and hyperuricaemia. In the present study, plasma ionized calcium (Ca2+) was studied in relation to cardiovascular risk factors in 20 subjects with mild hypertension. Plasma Ca2+ was found to be negatively correlated with fasting serum insulin, triglycerides and urate, and with diastolic blood pressure (DBP). However, after the interaction of the different risk factors had been taken into account in the multiple regression analysis, only the relationship between Ca2+ and serum insulin was significant (r = 0.55, P less than 0.01). In a previous double-blind, placebo-controlled study 1 micrograms alphacalcidol, a synthetic analogue of 1,25 dihydroxy-vitamin D3, induced a decrease in blood pressure in mild HPT subjects. In the present study, the highest dose that did not further aggravate the hypercalcaemia was given in a long-term study over a 12-month period to 18 mild HPT subjects (average dose, 1.75 micrograms daily). The treatment induced a reduction in body weight of 0.9 kg (P less than 0.05) and an increase in serum urate from 330 +/- 92 to 380 +/- 104 mmol l-1 (P less than 0.01). A reduction in blood pressure was only observed at the end of the study, from 142 +/- 17/86.6 +/- 9.1 to 139 +/- 13/82.9 +/- 8.9 mmHg (P less than 0.05 for DBP). The reduction in systolic blood pressure was significantly correlated with the reduction in body weight induced by treatment (r = 0.63, P less than 0.02). No consistent changes in glucose or lipid metabolism were induced by treatment. PMID- 1588271 TI - The predictive value of CKMB mass concentration in unstable angina pectoris: preliminary report. AB - Unstable angina pectoris is a common clinical problem, and the diagnosis is based on clinical symptoms. However, these symptoms cannot identify high-risk patients. Holter monitoring can identify patients at high risk, but analysis of a large number of patients is time- and resource-consuming, as is angiographic examination. We determined whether creatine kinase MB isoenzyme mass concentration could predict the prognosis for patients with unstable angina pectoris. A total of 101 consecutive patients were studied, and blood samples were collected three times a day for 48 h after admission. Patients with unstable angina and elevated CKMB (but still within the normal range) had a significantly higher risk of developing acute myocardial infarction or requiring revascularization during 6 months of follow-up than patients without elevated CKMB. We conclude that CKMB analysis is a valuable tool that may be of use in selecting high-risk patients with unstable angina pectoris. This finding needs to be confirmed by more extensive studies. PMID- 1588272 TI - Pseudomonas infections in patients with AIDS and AIDS-related complex. AB - We identified and reviewed retrospectively all the cases of infection by Pseudomonas and related genera in patients with AIDS and AIDS-related complex (ARC) who were hospitalized at our Institution over a 36-month period. We recorded 48 episodes of infection in 34 of 355 patients with AIDS, and in two of 73 patients with ARC: 25 pneumonias (9 community-acquired and 16 of nosocomial origin). 20 urinary tract infections, two soft tissue infections and one sepsis. In 14 of 16 patients with nosocomial pneumonia but in only one of nine patients with community-acquired pneumonia did we find coexisting opportunistic lung diseases. The following micro-organisms were isolated: P. aeruginosa in 41 cases, P. fluorescens in three cases, Xanthomonas maltophilia (P. maltophilia) in two cases, P. putida in one case. Comamonas testosteronis (P. testosteronis) and Comamonas acidovorans (P. acidovorans) in one case. Amikacin and ceftazidime, alone or in combination, appear to be the optimal choice of therapy for severe Pseudomonas infections in HIV-infected patients, although in our study six of 47 isolates were resistant in vitro to amikacin, and nine of 31 isolates were resistant to ceftazidime. PMID- 1588273 TI - A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability. AB - To be recognized by CD8+ T lymphocytes, target cells must process and present peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. The nonimmunogenic, low class I-expressing, methylcholanthrene (MCA) induced murine sarcoma cell line, MCA 101, is a poor presenter of endogenously generated viral antigens to specific CD8+ T lymphocytes and cannot be used to generate tumor infiltrating lymphocytes (TIL). Since interferon gamma (IFN-gamma) has been shown to upregulate three sets of molecules important for antigen processing and presentation, we retrovirally transduced wild-type MCA 101 (101.WT) tumor with the mIFN-gamma cDNA to create the 101.NAT cell line. Unlike 101.WT, some clones of retrovirally transduced 101.NAT tumor expressed high levels of class I, and could be used to generate CD8+ TIL. More importantly, these TIL were therapeutic in vivo against established pulmonary metastases from the wild-type tumor. Although not uniformly cytotoxic amongst several separate cultures, these TIL did specifically release cytokines (IFN-gamma and tumor necrosis factor-alpha) in response to 101.WT targets. 101.WT's antigen presentation deficit was also reversed by gene modification with mIFN-gamma cDNA. 101.NAT had a greatly improved capacity to present viral antigens to CD8+ cytotoxic T lymphocytes. These findings show that a nonimmunogenic tumor, incapable of generating a CD8+ T cell immune response, could be gene-modified to generate a therapeutically useful immune response against the wild-type tumor. This strategy may be useful in developing treatments for tumor histologies not thought to be susceptible to T cell-based immunotherapy. PMID- 1588274 TI - Differential expression of VH gene families in peripheral B cell repertoires of newborn or adult immunoglobulin H chain congenic mice. AB - The pattern of VH gene family expression in the primary B cell repertoire of the mouse is strain dependent. In C57Bl/6 mice, the VH J558 family is expressed by more than 45% of the cells, while the expression of VH 7183, VH Q52, and VH 36-60 families together does not exceed 20%. In BALB/c mice, relative expression of VH J558 is lower than 35%, while the sum of the other three families reaches 25%. To assess which genetic loci control strain-specific VH gene family expression, we studied VH gene family usage in splenic B cell repertoires of different congenic strains of mice. Changes in major histocompatibility complex or immunoglobulin (Ig) K light chain genes did not modify VH gene family expression in adult mice. Differences at the IgH locus, however, modified VH gene family usage. In 1-d-old mice, the strain-specific VH gene family expression pattern is determined by the IgH haplotype. In adult mice, the VH gene family expression pattern of resting B cells is independent of the IgH locus and follows the genetic background of the congenic strain, while it is determined by the IgH haplotype among Ig-secreting spleen cells. In F1(B6 x BALB/c) mice, each of the two spleen B cell populations, sorted on the basis of mu heavy chain allotype expression, shows an independent VH gene family expression pattern, determined by the IgH locus. The implications of these results in the control of VH gene family expression, and in the selection of peripheral B cell repertoires are discussed. PMID- 1588275 TI - The MRC OX-62 antigen: a useful marker in the purification of rat veiled cells with the biochemical properties of an integrin. AB - A mouse immunoglobulin G1 monoclonal antibody (mAb), MRC OX-62 (OX-62), was raised against density gradient-enriched rat veiled (dendritic) cells obtained from lymph. In suspensions of lymphoid cells, the OX-62 mAb only labeled cells with the characteristics of veiled cells. The OX-62 mAb was used with a magnetic cell sorter to enrich or deplete veiled cells, and the enriched veiled cells were potent stimulators in the primary allogeneic mixed leukocyte reaction. Immunohistochemical staining of tissue sections showed that the OX-62 mAb did not label all classical dendritic cells and was not restricted to this cell type. In lymphoid tissues, the labeling correlated with dendritic cells, but in skin, major histocompatibility complex class II+ cells were OX-62-, while another CD3+ cell with dendritic morphology was strongly OX-62+. It seems that the OX-62 mAb may be restricted to dendritic cells and probably to gamma/delta T cells. The OX 62 mAb will be of use in delineating minor subsets of cells with dendritic morphology in various tissues. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of veiled cell-enriched populations immunoprecipitated with the OX-62 mAb gave bands with the biochemical characteristics of an integrin. The OX-62 mAb recognized the alpha-like subunit. PMID- 1588276 TI - Listeriolysin O is a target of the immune response to Listeria monocytogenes. AB - The immunologic mechanism of protective immunity to the intracellular parasite Listeria monocytogenes (Lm) is not well understood, however, antilisterial immunity can be adoptively transferred with T lymphocytes from Lm-immune donors. The Lm-immune cells are believed to produce macrophage-activating lymphokines, which leads to the eventual macrophage-dependent eradication of the bacterium. Increasing evidence suggests that immunity to Lm resides exclusively within the CD8+ T cell subset. It is possible that the Lm-immune CD8+ T cells function to release sequestered Lm from nonprofessional phagocytes to awaiting activated macrophage populations. This study was conducted to determine if listeriolysin O (LLO), which is an essential determinant of Lm pathogenicity, is also a target of the antilisterial immune response. We have found that target cells infected with a LLO+ Lm strain are lysed by Lm-immune cytotoxic cells, whereas target cells infected with a LLO- Lm mutant, or pulsed with a heat-killed Lm preparation, are not lysed by the Lm-immune effector cells. We have used a Bacillus subtilis (Bs) construct that expresses the LLO gene product and found that target cells infected with the LLO+ Bs construct are lysed by antilisterial cytotoxic cells. The antilisterial cytotoxic response is targeted against LLO, in that we have also used a Bs construct that expresses the perfringolysin (PLO) gene product and found that target cells infected with the PLO+ Bs are not lysed by antilisterial cytotoxic effector cells. These data strongly suggest that LLO is a target antigen of antilisterial immunity and may represent the dominant target during the expression of the immune response to Lm. PMID- 1588277 TI - Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor. AB - The Staphylococcal enterotoxin superantigens stimulate vigorous responses in T cells bearing certain T cell antigen receptor (TCR) V beta regions. In addition to activation, these superantigens also impart negative signals to T cells resulting in a profound state of unresponsiveness or anergy. The Staphylococcus aureus enterotoxins (SE) B and C2 bind to a closely related site on major histocompatibility complex (MHC) human leukocyte antigen (HLA)-DR1 molecules. Only SEB, however, interacts with the TCR V beta 3 region of HA1.7, a human HLA DR1 restricted T cell clone specific for influenza haemagglutinin. In competition experiments, we demonstrated that the induction of anergy in HA1.7 by SEB is unaffected by the presence of SEC2. These results suggest that SEB-induced anergy is MHC independent and involves a direct interaction between the TCR and SEB. To resolve definitively whether SEB binds directly to T cells in the absence of MHC class II molecules, the cDNAs encoding the HA1.7 TCR were transfected into an MHC class II-negative human T cell line. The addition of SEB to these transfectants resulted in the downregulation of cell surface TCR expression, an increase in the concentration of intracellular calcium ions, the production of lymphokines, and reduced responsiveness to a subsequent challenge with SEB. We conclude that SEB interacts directly with the TCR in the absence of cointeraction with MHC class II molecules, and that this interaction may induce anergy in HA1.7. PMID- 1588278 TI - Rejection of skin allografts by indirect allorecognition of donor class I major histocompatibility complex peptides. AB - LEW (RT1l) rats were immunized with peptides corresponding to the alpha helical region of the alpha 1 domain (peptide 1), the beta sheet of the alpha 2 domain (peptide 2), and the alpha helical region of the alpha 2 domain (peptide 3) of the RT1-Aav1 classical class I molecule of the DA (RT1av1) strain. The immunizations were without carriers, and the objective was to prime to indirect allorecognition without influencing direct recognition of the RT1-Aav1 molecule. The LEW rats mounted strong primary and secondary antibody responses to peptides 1 and 3, but only weak secondary responses to peptide 2. None of the antipeptide antibodies crossreacted with intact RT1-Aav1 class I molecules. The immunization also resulted in LEW antigen-presenting cell-dependent, CD4+ T cell proliferative responses, which were very strong against peptide 1 and weakest against peptide 2. LEW rats immunized with peptides 1 or 3, but most effectively with both peptides 1 and 3 together, showed accelerated rejection of DA skin allografts. This effect was not observed in LEW rats immunized with peptide 2. In response to the DA skin allograft, the peptide-immunized LEW rats showed markedly accelerated kinetics of antibody production to the intact RT1-Aav1 molecule. These data demonstrate that indirect allorecognition can play an important role in allograft rejection and have important implications for understanding allograft rejection and its regulation. PMID- 1588279 TI - Biased distribution of recombination sites within S regions upon immunoglobulin class switch recombination induced by transforming growth factor beta and lipopolysaccharide. AB - We have characterized extrachromosomal circular DNAs from adult mouse spleen cells that were induced to switch to immunoglobulin A (IgA) with bacterial lipopolysaccharide (LPS) and transforming growth factor beta (TGF-beta), and identified breakpoints of S mu/S gamma 3, S mu/S gamma 2, S mu/S alpha, S gamma 3/S alpha, and S gamma 2/S alpha recombinants. The S mu recombination donor sites clustered in the 3' half of the S mu region, while the S alpha recombination acceptor sites clustered in the 5' half of the S alpha region. In addition, donor and acceptor sites of S gamma regions also clustered in the 3' and 5' parts, respectively. These site preferences are in sharp contrast to the dispersed distribution of S mu/S gamma 1 breakpoints within both S mu and S gamma 1 regions upon IgG1 switch induced by LPS and interleukin 4. Our results support the hypotheses that TGF-beta increases the frequency of switch recombination events to IgA and that the switch recombination to IgA often proceeds by successive recombination of S mu/S gamma and S gamma/S alpha. PMID- 1588280 TI - Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism. AB - The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. This reaction is controlled by the regulators of C activation protein family. Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. As a widely distributed membrane protein, MCP may protect host cells from inadvertent C activation. Human MCP has recently been shown to protect transfected rodent cells from human C mediated lysis. In this report the relationship of MCP expression to C3b deposition and cytoprotection was examined using NIH/3T3 cells transfected with human MCP and exposed to human serum as a source of C and naturally occurring anti-mouse antibody. MCP inhibited C3b deposition in a dose-dependent fashion and inhibited lysis of the mouse cells expressing it. MCP did not inhibit lysis on bystander cells. These results demonstrate the protective role of MCP, at the cellular level, by an intrinsic mechanism. PMID- 1588282 TI - BCL2 oncogene translocation is mediated by a chi-like consensus. AB - Examination of 64 translocations involving the major breakpoint region (mbr) of the BCL2 oncogene and the immunoglobulin heavy chain locus identified three short (14, 16, and 18 bp) segments within the mbr at which translocations occurred with very high frequency. Each of these clusters was associated with a 15-bp region of sequence homology, the principal one containing an octamer related to chi, the procaryotic activator of recombination. The presence of short deletions and N nucleotide additions at the breakpoints, as well as involvement of JH and DH coding regions, suggested that these sequences served as signals capable of interacting with the VDJ recombinase complex, even though no homology with the traditional heptamer/spacer/nonamer (IgRSS) existed. Furthermore, the BCL2 signal sequences were employed in a bidirectional fashion and could mediate recombination of one mbr region with another. Segments homologous to the BCL2 signal sequences flanked individual members of the XP family of diversity gene segments, which were themselves highly overrepresented in the reciprocal products (18q-) of BCL2 translocation. We propose that the chi-like signal sequences of BCL2 represent a distinct class of recognition sites for the recombinase complex, responsible for initiating interactions between regions of DNA separated by great distances, and that BCL2 translocation begins by a recombination event between mbr and DXP chi signals. Since recombinant joints containing chi, not IgRSS, occur in brain cells expressing RAG-1 (Matsuoka, M., F. Nagawa, K. Okazaki, L. Kingsbury, K. Yoshida, U. Muller, D. T. Larue, J. A. Winer, and H. Sakano. 1991. Science [Wash. DC]. 254:81; reference 1), we further suggest that the product of this gene could mediate both BCL2 translocation and the first step of normal DJ assembly through the creation of chi joints, rather than signal or coding joints. PMID- 1588281 TI - Functional analysis of the antigen binding site on the T cell receptor alpha chain. AB - We have identified residues on a T cell receptor (TCR) alpha chain that are important for interaction with antigen/major histocompatibility complex (MHC). Using site-directed mutagenesis, we modified DNA encoding the postulated antigen/MHC binding loops on the TCR alpha chain expressed by the T cell clone D5, which recognizes p-azobenzenearsonate-conjugated antigens presented by cells bearing I-Ad. These variant TCR alpha chains were expressed in conjunction with the wild-type D5 TCR beta chain on the surface of hybridoma cells, and were tested for the ability to recognize hapten-conjugated antigens presented by I-Ad. Individual amino acid substitutions in each of the three antigen binding loops (alpha 1, alpha 2, alpha 3) of the D5 TCR alpha chain affected antigen recognition, demonstrating that all three loops are important in recognition of antigen/MHC. A subset of the single amino acid substitutions completely eliminated antigen recognition, thus identifying the residues that are particularly important in the recognition of antigenic peptide/MHC by the D5 TCR. Because the wild-type D5 TCR recognizes arsonate and certain structural analogues of arsonate conjugated to a variety of protein antigens, we were able to test whether the TCR substitutions affected the specificity of the D5 TCR for hapten or carrier antigen. One substitution introduced into antigen binding loop alpha 3 markedly altered the pattern of carrier recognition. Together, these results verify the Ig model for the TCR and are consistent with the proposition that residues forming the first and second antigen binding loops of the TCR contact the MHC, while those forming the third loop contact mainly antigenic peptides. PMID- 1588283 TI - CD4 T cells in murine acquired immunodeficiency syndrome: polyclonal progression to anergy. AB - We have examined the kinetics of changes that occur in the helper T cell subset during murine acquired immunodeficiency syndrome, which occurs after infection with the mix of viruses known as BM5. We find that there is expansion of the CD4 T cells by 2 wk, 50% of the CD4 T cells become large as the disease progresses, and the CD4 T cell population is increasingly comprised of cells with a memory/activated phenotype. These effects are apparent by 2 wk postinfection, and the change is nearly complete by 6-8 wk. The phenotypic shift is paralleled by the loss of the ability of the CD4 T cells to proliferate or to produce interleukin 2 (IL-2), IL-3, IL-4, and interferon gamma in response to stimulation with mitogens, superantigen, or anti-CD3. There is no obvious expansion or deletion of CD4 T cells expressing particular V beta genes, as might be expected if a conventional superantigen were driving the changes. The results suggest, however, that the total CD4 population has been driven to anergy by some potent polyclonal stimulus directly associated with viral infection. PMID- 1588284 TI - Developmentally regulated infectivity of malaria sporozoites for mosquito salivary glands and the vertebrate host. AB - Sporozoites are an invasive stage of the malaria parasite in both the mosquito vector and the vertebrate host. We developed an in vivo assay for mosquito salivary gland invasion by preparing Plasmodium gallinaceum sporozoites from infected Aedes aegypti mosquitoes under physiological conditions and inoculating them into uninfected female Ae. aegypti. Sporozoites from mature oocysts were isolated from mosquito abdomens 10 or 11 d after an infective blood meal. Salivary gland sporozoites were isolated 13 or 14 d after an infective blood meal. Purified oocyst sporozoites that were inoculated into uninfected female mosquitoes invaded their salivary glands. Using the same assay system, sporozoites derived from salivary glands did not reinvade the salivary glands after inoculation. Conversely, as few as 10 to 50 salivary gland sporozoites induced infection in chickens, while only 2 of 10 chickens inoculated with 5,000 oocyst sporozoites were infected. Both sporozoite populations were found to express a circumsporozoite protein on the sporozoite surface as determined by immunofluorescence assay and circumsporozoite precipitation test using a circumsporozoite protein-specific monoclonal antibody. We conclude that molecules other than this circumsporozoite protein may be responsible for the differential invasion of mosquito salivary glands or infection of the vertebrate host. PMID- 1588285 TI - A role for complement receptor-like molecules in iron acquisition by Candida albicans. AB - Candida albicans, an opportunistic fungal pathogen of humans, is dependent upon iron for growth. Consequently, human serum inhibits C. albicans growth due to the presence of high affinity iron-binding proteins that sequester serum iron, making it unavailable for use by the organism. We report that in the inhibitory environment of human serum, the growth of C. albicans can be restored by the addition of exogenous hemoglobin or heme, but not by protoporphyrin IX, the heme precursor that does not contain iron. We further report that C. albicans can utilize cell surface proteins that are homologues of the mammalian complement receptors (CR) to rosette complement-coated red blood cells (RBC) and obtain RBC derived iron for growth. The ability of Candida to acquire RBC-derived iron under these conditions is dependent upon Candida-RBC rosetting mediated by CR-like molecules. Unopsonized RBC do not support Candida growth in serum, and restoration of Candida growth in serum by complement-opsonized RBC is inhibited by monoclonal antibodies to the human CR type 3 (CR3). In addition, activation of the human alternative pathway of complement by Candida leads to "bystander" deposition of C3 fragments on the surface of autologous, unopsonized RBC, generating the ligands necessary for Candida-RBC rosetting. These results suggest that C. albicans has evolved a unique strategy for acquiring iron from the host, which exploits the host complement system, and which may contribute to the pathogenic potential of the organism. PMID- 1588286 TI - Efficient dissociation of the p88 chaperone from major histocompatibility complex class I molecules requires both beta 2-microglobulin and peptide. AB - Previously, we showed that an 88-kD protein (p88) associates rapidly and quantitatively with newly synthesized murine major histocompatibility complex class I molecules within the endoplasmic reticulum (ER). This interaction is transient and dissociation of p88 appears to be rate limiting for transport of class I molecules from the ER to the Golgi apparatus. In this report, we examine the relationship between p88 interaction and assembly of the ternary complex of class I heavy chain beta 2-microglobulin (beta 2m), and peptide ligand. In both murine and human beta 2m-deficient cells, in which little or no transport of class I heavy chains is observed, p88 remained associated with intracellular heavy chains throughout their lifetime. In murine RMA-S cells, which are apparently defective in accumulating peptide ligands for class I within the ER, prolonged association of p88 with "empty" heavy chain-beta 2m heterodimers was also observed. However, p88 dissociated slowly in parallel with the slow rate of ER to Golgi transport of empty class I molecules in these cells. The close correlation between p88 association and impaired class I transport suggests that p88 functions to retain incompletely assembled class I molecules in the ER. We propose that conformational changes in class I heavy chains induced by the binding of both beta 2m and peptide are required for efficient p88 dissociation and subsequent class I transport. PMID- 1588287 TI - Functional reconstitution of an immunoglobulin antigen receptor in T cells. AB - Humoral immune responses are initiated by binding of antigen to the immunoglobulins (Igs) on the plasma membrane of B lymphocytes. On the cell surface, Ig forms a complex with several other proteins, two of which, MB-1 and B29, have been implicated in receptor assembly. We have reconstituted Ig receptor function in T lymphocytes by transfection of cloned receptor components. We found that efficient transport of IgM to the surface of T cells required coexpression of B29. Furthermore, IgM and B29 alone were sufficient to reconstitute antigen specific signal transduction by Ig in the transfected T cells. Crosslinking of IgM with either antireceptor antibodies or antigen induced a calcium flux, phosphoinositol turnover, and interleukin secretion in T cells. These experiments establish a requirement for B29 in Ig receptor function, and suggest that the signaling apparatus of T and B cells is structurally homologous. PMID- 1588288 TI - CD4+ T cells cause multinucleated giant cells to form around Cryptococcus neoformans and confine the yeast within the primary site of infection in the respiratory tract. AB - The possible mechanisms by which CD4+ T cells prevent the dissemination of Cryptococcus neoformans from the primary site of infection in the respiratory tract were examined. It was found that even before fungicidal mechanisms are fully induced in the lungs, the host generates a CD4+ T cell-dependent inflammatory response that sequesters yeast within the pulmonary alveoli. This confinement is evident histopathologically and demonstrable objectively as a rapid decline in the ability to dislodge yeast from the lungs by bronchopulmonary lavage. One striking component of this response is the enclosure of cryptococci within multinucleated giant cells in granulomas. Studies in severe combined immunodeficient mice that were engrafted with selected lymphocyte subpopulations show that B cells, and hence anti-Cryptococcus antibodies, are not necessary for the CD4+ T cell-dependent responses that isolate and subsequently destroy this opportunistic pathogen in the lung parenchyma. PMID- 1588289 TI - Novel responses of human skin to intradermal recombinant granulocyte/macrophage colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. AB - Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged. PMID- 1588290 TI - Prolonged treatment with recombinant interferon gamma induces erythema nodosum leprosum in lepromatous leprosy patients. AB - 10 patients with borderline and lepromatous leprosy were selected for a prolonged trial with recombinant interferon gamma (rIFN-gamma). Patients received 30 micrograms intradermally for six injections over a 9-d period, and then either 100 micrograms intradermally every 1 mo for 10 mo or every 2 wk for 5 mo (total, 1.2 mg). Erythema nodosum leprosum (ENL) was induced in 60% of the patients within 6-7 mo, as compared with an incidence of 15% per year with multiple drug therapy alone. The mean whole-body reduction in bacterial index over the first 6 mo was 0.9 log units. Cutaneous induration at the intradermal injection sites of greater than or equal to 15 mm predicted the development of a subsequent reactional state. Monocytes obtained from patients receiving the lymphokine demonstrated an increased respiratory burst and a 2.5-5.1-fold increase in tumor necrosis factor alpha (TNF-alpha) secretion in response to agonists. Patients in ENL had an even higher release of TNF-alpha from monocytes as well as high levels of TNF-alpha in the plasma (mean, 2,000 pg/ml). Thalidomide therapy was required to treat the systemic manifestations of ENL. Control of toxic symptoms with thalidomide was associated with a 50-80% reduction in agonist-stimulated monocyte TNF-alpha secretion. IFN-gamma enhanced the monocyte release of TNF-alpha by 3 7.5-fold (agonist dependent) when added to patient's cells in vitro, and this could be suppressed by the in vitro addition of 10 micrograms/ml of thalidomide. PMID- 1588293 TI - Can we rationally ration health care? PMID- 1588291 TI - VLA-4-fibronectin interaction is required for the terminal differentiation of human bone marrow cells capable of spontaneous and high rate immunoglobulin secretion. AB - Human bone marrow (BM) is a relevant site for immunoglobulin (Ig) generation in vivo. The occurrence of BM cells capable of spontaneous and high rate Ig secretion for 14 d in vitro has been described previously. Accordingly, these cells provide a suitable model for studying terminal B cell maturation within the BM. We have reported recently that these BM cells are not totally differentiated when isolated from the body, as they require inductive signals from adherent stromal BM cells to complete their maturation. Interleukin (IL)-6 produced by these adherent BM cells was identified as one such signal. The present work shows that IL-6 was necessary, but not sufficient, for the induction of BM Ig-secreting cells, since the cytokine was unable to restore missing IgG in nonadherent BM cell cultures. Supernatants (SN) obtained from cultures of stromal adherent BM cells, either freshly isolated or derived from long-term BM culture (LTBMC), restored Ig secretion by nonadherent BM cells, suggesting that additional soluble factors from BM stromal cells were required. Fibronectin (FN) was identified as that factor, as can be deduced from the following findings: (a) stromal, but not nonadherent, BM cells constitutively produced FN; (b) anti-FN antibodies markedly reduced the IgG secretion in cultures of BM mononuclear cells (BMMC), and blocked the inductive effect of stromal cell SN on nonadherent BM cells, and such a blockade could be reversed by exogenous FN; and (c) finally, although neither IL 6 nor FN alone exerted any effect, the combination of both factors induced optimal Ig secretion by nonadherent BM cells. Furthermore, VLA-4 molecules seemed to be the FN receptor that was active in this culture system, as indicated by: (a) BM Ig-secreting cells exhibited the phenotype VLA-4+ VLA-5-; (b) mAbs directed to VLA-4 (anti-CD29 and anti-CD49d), but not those directed to other adhesion molecules, inhibited Ig secretion by BMMC cultures, and this effect was reversed by FN; (c) the inductive role of the entire FN molecule could be replaced by a fragment containing the CS-1 region, but not by a fragment containing the RGDS sequence; and (d) only mAbs anti-CD49d capable of blocking VLA-4-FN interaction inhibited induction by either the FN or the CS-1-containing fragment of FN.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588292 TI - Cloning and expression of class I major histocompatibility complex genes of the rat. AB - Little is known about the organization of class I genes in the rat although there is prima facie evidence that it is distinct from that of the mouse. We report the cloning of 61 nonclassical rat class I genes into cosmid clusters with a total mapped length of 1,264 kb. It is certain that the total number of class I genes in the rat must exceed this number. From restriction maps it is possible to identify substantial regions of duplication. By transfection of cosmids into mouse L cells, it has been possible to demonstrate at least seven different nonclassical rat class I genes that are expressible on the cell surface. Crossreaction of a single mouse monoclonal antibody with all of these class I molecules is consistent with sequence homogenization within the rat nonclassical system. Attempts to find rat homologues of the mouse Tla genes by crosshybridization of rat cosmids with a range of different TLa-specific probes were unsuccessful, suggesting that this large group of divergent class I genes is absent or nearly so from the rat. The large number of class I genes in the rat appears to have arisen by expansion of genes more closely related to the classical sequence. PMID- 1588294 TI - Hypothyroidism and hyperthyroidism in the elderly. AB - Thyroid disease in the elderly can be easily overlooked. Symptoms too often are explained away as normal processes of aging. Development of unstable illness, especially cardiac disease, is a frequent mode of presentation. One symptom or one clinical feature of thyroid disease in the elderly may be overwhelming in its presentation, as in apathetic hyperthyroidism, thyroid myopathy, depression and dementia. Physical examination of the thyroid gland can be helpful but in a high percentage of older patients the gland is normal to palpation. The treatment of hypothyroidism is straightforward. Only myxedema coma requires large doses of levothyroxine parenterally; all other forms of hypothyroidism are treated with oral levothyroxine. The dose is started very low and increased gradually over months. The euthyroid state is achieved gradually and safely. Hyperthyroidism can be treated by several modalities. In the unstable elderly patient, antithyroid medication can quickly produce a euthyroid state. When the patient is stable, further decisions can be made regarding definitive therapy. Radioactive iodine therapy is well-tolerated and effective. On occasion, a second course of therapy is needed to suppress hyperthyroidism. Close follow-up of all patients ever having received this therapy is needed to identify the development of hypothyroidism. Surgical thyroid ablation may be necessary in patients who fail to respond to radioactive iodine therapy. Abnormalities associated with unresolved thyromegaly, dysphagia, or tracheal compression may require surgical intervention. If suspicion exists that the gland is cancerous, surgical intervention is warranted. PMID- 1588295 TI - Progesterone in diagnosis of ectopic pregnancy. AB - Previous reports suggest that serum progesterone value may be useful in the diagnosis of ectopic pregnancy. These studies have based discriminatory thresholds on a limited number of patients without using statistical correction for biologic variability in an infinitely large population. This study was designed to determine the ability of a single progesterone value to discriminate between normal, ectopic and blighted pregnancies. Sera were obtained from all positive beta HCG tests at Shands Hospital, University of Florida. All samples were assayed simultaneously with a solid phase RIA for progesterone and the results compared with pregnancy outcome. The mean progesterone for normal pregnancies was 32.8 +/- 4.25 ng/ml (n = 49), for ectopic pregnancies 7.8 +/- 0.79 ng/ml (n = 51), and pregnancies which spontaneously aborted 8.1 +/- 0.91 ng/ml (n = 74). Using individual prediction limits progesterone greater than 24 ng/ml would exclude an ectopic pregnancy in 99% of patients. Thus, this test may be useful in selected patients when the diagnosis is unsure after beta HCG and transvaginal ultrasound have been performed. PMID- 1588296 TI - Patient Self-Determination Act. AB - The Patient Self-Determination Act (PSDA) took effect December 1, 1991. As a direct result of the Nancy Cruzan case, this Act is intended to promote awareness and discussion of health-care issues in preparation for medical decisions at the end of life. The mechanism is the federal requirement that any health-care institution which expects to receive Medicare or Medicaid funds must inform patients upon admission of state laws governing self-determination issues. Any discussion among patients, families and their physicians stimulated by the PSDA is healthy. Physicians must be prepared for new questioning by patients about self-determination issues and must be knowledgeable of state laws. They must also defend against bureaucratization of medical decision-making by taking a leadership role in the patient autonomy movement, injecting into the movement an awareness of the rational capacity of medical technology. PMID- 1588297 TI - Pesticide sensitivity registry. What doctors need to know. AB - Commercially used lawn and home pesticides may cause a variety of symptoms in sensitive individuals. To assist those individuals considered at risk, the Florida Department of Health and Rehabilitative Services (HRS) has developed a process of registering persons sensitive to pesticides, providing they submit certification of their sensitivity by a qualified medical specialist. Pesticide applicators are required by law to inform registered persons of pesticide application to a lawn or exterior foliage on properties contiguous with or adjacent to a registered person at least 24 hours prior to application of the pesticide. PMID- 1588298 TI - When a doctor plays judge. PMID- 1588299 TI - Tests are extensions of physical examinations. PMID- 1588300 TI - Pseudo-streaming potentials in Necturus gallbladder epithelium. II. The mechanism is a junctional diffusion potential. AB - The mechanisms of apparent streaming potentials elicited across Necturus gallbladder epithelium by addition or removal of sucrose from the apical bathing solution were studied by assessing the time courses of: (a) the change in transepithelial voltage (Vms). (b) the change in osmolality at the cell surface (estimated with a tetrabutylammonium [TBA+]-selective microelectrode, using TBA+ as a tracer for sucrose), and (c) the change in cell impermeant solute concentration ([TMA+]i, measured with an intracellular double-barrel TMA(+) selective microelectrode after loading the cells with TMA+ by transient permeabilization with nystatin). For both sucrose addition and removal, the time courses of Vms were the same as the time courses of the voltage signals produced by [TMA+]i, while the time courses of the voltage signals produced by [TBA+]o were much faster. These results suggest that the apparent streaming potentials are caused by changes of [NaCl] in the lateral intercellular spaces, whose time course reflects the changes in cell water volume (and osmolality) elicited by the alterations in apical solution osmolality. Changes in cell osmolality are slow relative to those of the apical solution osmolality, whereas lateral space osmolality follows cell osmolality rapidly, due to the large surface area of lateral membranes and the small volume of the spaces. Analysis of a simple mathematical model of the epithelium yields an apical membrane Lp in good agreement with previous measurements and suggests that elevations of the apical solution osmolality elicit rapid reductions in junctional ionic selectivity, also in good agreement with experimental determinations. Elevations in apical solution [NaCl] cause biphasic transepithelial voltage changes: a rapid negative Vms change of similar time course to that of a Na+/TBA+ bi-ionic potential and a slow positive Vms change of similar time course to that of the sucrose-induced apparent streaming potential. We conclude that the Vms changes elicited by addition of impermeant solute to the apical bathing solution are pseudo-streaming potentials, i.e., junctional diffusion potentials caused by salt concentration changes in the lateral intercellular spaces secondary to osmotic water flow from the cells to the apical bathing solution and from the lateral intercellular spaces to the cells. Our results do not support the notion of junctional solute solvent coupling during transepithelial osmotic water flow. PMID- 1588301 TI - Chemosensory responses in isolated olfactory receptor neurons from Necturus maculosus. AB - Olfactory receptor neurons were isolated without enzymes from the mudpuppy, Necturus maculosus, and tested for chemosensitivity. The cells responded to odorants with changes in firing frequency and alterations in excitability that were detected with tight-seal patch electrodes using on-cell and whole-cell recording conditions. Chemosensitive cells exhibited two primary response characteristics: excitation and inhibition. Both types of primary response were observed in different cells stimulated by mixtures of amino acids as well as by the single compound L-alanine, suggesting that there may be more than one transduction pathway for some odorants. Using the normal whole-cell recording method, the chemosensitivity of competent cells washed out rapidly; a resistive whole-cell method was used to record odorant responses under current-clamp conditions. In response to chemical stimulation, excitability appeared to be modulated in several different ways in different cells: odorants induced hyperpolarizing or depolarizing receptor potentials, elicited or inhibited transient, rhythmic generator potentials, and altered excitability without changing the membrane potential or input resistance. These effects suggest that olfactory transduction is mediated through at least three different pathways with effects on four or more components of the membrane conductance. Polychotomous pathways such as these may be important for odor discrimination and for sharpening the "odor image" generated in the olfactory epithelium. PMID- 1588302 TI - Cellular NH4+/K+ transport pathways in mouse medullary thick limb of Henle. Regulation by intracellular pH. AB - Fluorescence and electrophysiological methods were used to determine the effects of intracellular pH (pHi) on cellular NH4+/K+ transport pathways in the renal medullary thick ascending limb of Henle (MTAL) from CD1 mice. Studies were performed in suspensions of MTAL tubules (S-MTAL) and in isolated, perfused MTAL segments (IP-MTAL). Steady-state pHi measured using 2,7-biscarboxyethyl-5(6) carboxyfluorescein (BCECF) averaged 7.42 +/- 0.02 (mean +/- SE) in S-MTAL and 7.26 +/- 0.04 in IP-MTAL. The intrinsic cellular buffering power of MTAL cells was 29.7 +/- 2.4 mM/pHi unit at pHi values between 7.0 and 7.6, but below a pHi of 7.0 the intrinsic buffering power increased linearly to approximately 50 mM/pHi unit at pHi 6.5. In IP-MTAL, NH4+ entered cells across apical membranes via both Ba(2+)-sensitive pathway and furosemide-sensitive Na+:K+(NH4+):2Cl- cotransport mechanisms. The K0.5 and maximal rate for combined apical entry were 0.5 mM and 83.3 mM/min, respectively. The apical Ba(2+)-sensitive cell conductance in IP-MTAL (Gc), which reflects the apical K+ conductance, was sensitive to pHi over a pHi range of 6.0-7.4 with an apparent K0.5 at pHi approximately 6.7. The rate of cellular NH4+ influx in IP-MTAL due to the apical Ba(2+)-sensitive NH4+ transport pathway was sensitive to reduction in cytosolic pH whether pHi was changed by acidifying the basolateral medium or by inhibition of the apical Na+:H+ exchanger with amiloride at a constant pHo of 7.4. The pHi sensitivities of Gc and apical, Ba(2+)-sensitive NH4+ influx in IP-MTAL were virtually identical. The pHi sensitivity of the Ba(2+)-sensitive NH4+ influx in S MTAL when exposed to (apical+basolateral) NH4Cl was greater than that observed in IP-MTAL where NH4Cl was added only to apical membranes, suggesting an additional effect of intracellular NH4+/NH3 on NH4+ influx. NH4+ entry via apical Na+:K+ (NH4+):2Cl- cotransport in IP-MTAL was somewhat more sensitive to reductions in pHi than the Ba(2+)-sensitive NH4+ influx pathway; NH4+ entry decreased by 52.9 +/- 13.4% on reducing pHi from 7.31 +/- 0.17 to 6.82 +/- 0.14. These results suggest that pHi may provide a negative feedback signal for regulating the rate of apical NH4+ entry, and hence transcellular NH4+ transport, in the MTAL. A model incorporating these results is proposed which illustrates the role of both pHi and basolateral/intracellular NH4+/NH3 in regulating the rate of transcellular N H4+ transport in the MTAL. PMID- 1588303 TI - Nucleotide sequence of the structural gene encoding a 2-haloalkanoic acid dehalogenase of Pseudomonas putida strain AJ1 and purification of the encoded protein. AB - The nucleotide sequence of a gene encoding an L-2-haloalkanoic acid halidohydrolase from Pseudomonas putida strain AJ1 was determined. The ORF (hadL) codes for a polypeptide of 227 amino acids (Mr 25,687) which has significant homology to two other L-2-haloalkanoic acid halidohydrolases of Pseudomonas sp., DehcI and DehcII; these show 38% and 51% amino acid identity respectively to HadL. All three enzymes produce products of an opposite optical configuration to that of the substrates. Comparison of the three sequences shows several highly conserved motifs which indicate the possible position of the enzyme active site. The enzyme was purified to homogeneity and appears to exist as a tetramer. PMID- 1588304 TI - Identification, characterization and sequence analysis of the gene encoding phosphoenolpyruvate carboxylase in Anabaena sp. PCC 7120. AB - The gene (ppc) encoding phosphoenolpyruvate carboxylase (PEPCase) in the cyanobacterium Anabaena sp. PCC 7120 has been isolated, characterized and its nucleotide sequence determined. Heterologous hybridization using the Synechococcus sp. PCC 7942 ppc gene as a probe of an Anabaena genomic DNA library identified an 8.2 kb HindIII DNA fragment that contained a 3.08 kb open reading frame encoding the cyanobacterial PEPCase. Deletion analysis of the 8.2 kb DNA fragment was used to determine sequences required for expression of enzyme activity in Escherichia coli cells. Primer extension data have been used to identify the cyanobacterial transcription initiation site and the position of the ppc start codon. Comparisons of the Anabaena deduced amino acid sequence with the Synechococcus sp. PCC 6301, E. coli and higher-plant ppc sequences have also been performed and the data are discussed with respect to conservation of specific regions of the protein. PMID- 1588305 TI - Cloning and partial sequencing of the proteinase gene complex from Lactococcus lactis subsp. lactis UC317. AB - The proteinase genes from Lactococcus lactis subsp. lactis UC317 were identified on a plasmid, pCI310, which is a deletion derivative of a cointegrate between pCI301, the 75 kb Lac Prt plasmid from UC317 and the 38.5 kb cryptic plasmid from that strain. The prt genes were cloned using a replacement cloning strategy whereby fragments from pCI310 were exchanged with the equivalent fragments in pNZ521, which contains the cloned proteinase genes from L. lactis subsp. lactis SK112. This generated two plasmids which encoded a cell-envelope-associated and a secreted proteinase, respectively. Specific regions of the UC317 structural prtP gene known to encode seven of the amino acids essential for substrate cleavage specificity were sequenced and compared with the known sequences of prt genes from L. lactis strains SK112, Wg2 and NCDO763. In spite of various differences that were detected in the nucleotide sequence of this region, it appears that these seven amino acids in strains UC317 and NCDO763 are identical, and represent a combination of three of the amino acids from SK112 and four from Wg2. These results indicate that the UC317 proteinase is a natural hybrid of the SK112 and Wg2 proteinases. PMID- 1588306 TI - Expression of the B subunit of Escherichia coli heat-labile enterotoxin in a marine Vibrio and in a mutant that is pleiotropically defective in the secretion of extracellular proteins. AB - A marine Vibrio (designated Vibrio sp. 60) that is related to Vibrio anguillarum was used as a host for a plasmid that encodes the non-toxic B subunit (EtxB) of Escherichia coli heat-labile enterotoxin. Expression of EtxB in Vibrio sp. 60 resulted in the efficient and selective secretion of the B subunit into the extracellular growth medium. This indicated that Vibrio sp. 60, which does not normally produce cholera-like enterotoxins, nonetheless possesses a secretory machinery that permits these toxins to be translocated across its cytoplasmic and outer membranes. Expression of EtxB in a sec mutant of Vibrio sp. 60 (MVT1192), which had previously been shown to be defective in the secretion of several extracellular proteins, resulted in approximately 95% of the B subunit remaining entrapped within the periplasm of the bacterial cell envelope. This implies that the mutation in MVT1192 defines a locus that determines a common step in the secretion of extracellular proteins, including oligomeric toxins. PMID- 1588307 TI - Specificity of the Pseudomonas aeruginosa PAO1 lipoprotein I gene as a DNA probe and PCR target region within the Pseudomonadaceae. AB - The lipoprotein I gene (oprI) of Pseudomonas aeruginosa PAO1 was cloned and sequenced. A high degree of homology was found between our cloned PAO1 gene sequence and two published oprI sequences. Specific oligonucleotides were designed to amplify the oprI gene by the polymerase chain reaction (PCR). The potential of either the complete gene sequence or the specific oligonucleotide primers as a tool for rapid strain identification was directly assessed against bacterial colonies by PCR or against purified genomic DNA by Southern blot analysis, using a number of representative strains within the Pseudomonadaceae. The oprI gene was found to be well conserved within RNA group I. PMID- 1588308 TI - Analysis of surface proteins of Listeria in relation to species, serovar and pathogenicity. AB - SDS extracts of whole bacteria, representing five species and 15 serovars of Listeria, were analysed by SDS-PAGE and by immunoblotting with serum directed against whole formalin-treated L. monocytogenes. Profiles of L. monocytogenes were very different from those of other species of Listeria (i.e. L. innocua,L.welshimeri, L. seeligeri and L. ivanovii). This low degree of similarity between species was found even in the case of common serovars. Within the species L. monocytogenes, protein patterns were characterized, on the one hand, by a high degree of homogeneity between all strains of the same serovar and, on the other hand, by large differences between serovars, especially between sv. 1/2 and 4b. Thus we have identified major, surface-located protein antigens, specific for L. monocytogenes, either common to all serovars (64 and 68 kDa) or characteristic of certain serovars: 98 kDa for sv. 1/2 and 3; 76 and 78 kDa for sv. 4b, 4d and 4e; and 80 and 100 kDa for sv. 4a and 4c. Moreover, some of these bands (68 and 98 kDa) might be related to virulence, since differences were noticed between the profiles of haemolytic L. monocytogenes vs. 1/2a differing only in their virulence for immunocompromised mice. All these results confirmed, for the first time, the classification of Listeria obtained previously by genomic studies. They should help in the identification of new virulence factors and the development of easier and more specific methods of detection and identification. PMID- 1588309 TI - Presence of exposed phospholipids in the outer membrane of Vibrio cholerae. AB - Vibrio cholerae 569B was found to be highly sensitive to a wide range of chemicals, particularly hydrophobic compounds and neutral and anionic detergents. The phospholipid profile of the outer membrane was similar to that reported for other Gram-negative bacteria. The lipopolysaccharide (LPS) contained O-antigenic sugars and exhibited heterogeneity. In addition, the LPS moiety was characterized by a relatively low negative charge. Analysis by topological probes revealed the presence of a significant amount of exposed phospholipids in the outer membrane. The reduced negative charge of LPS molecules and the exposed phospholipids present in the outer membrane could be important in the increased permeation of exogenous compounds in V. cholerae. PMID- 1588310 TI - Purification and characterization of TDP-D-glucose 4,6-dehydratase from anthracycline-producing streptomycetes. AB - TDP-D-glucose 4,6-dehydratase, which converts TDP-D-glucose to TDP-D-4-keto-6 deoxyglucose, was purified to near-homogeneity from the daunorubicin and baumycin producing organism Streptomyces sp. C5 (968-fold purification with a 41% recovery), and from the daunorubicin producer Streptomyces peucetius ATCC 29050 (1000-fold purification with a 37% recovery). The TDP-D-glucose 4,6-dehydratases from Streptomyces sp. C5 and S. peucetius were determined by SDS-PAGE and HPLC gel filtration to be homodimers with subunit relative molecular masses of 39,000 and 36,000, respectively. For the enzymes from both organisms, negligible activity was observed in the absence of added NAD+, or when ADP-glucose, ADP mannose, GDP-mannose, UDP-glucose or UDP-galactose was substituted for TDP-D glucose as substrate. For the enzyme from Streptomyces sp. C5, the K'm values for NAD+ and TDP-D-glucose were 19.2 microM and 31.3 microM, respectively. The V'max for TDP-D-glucose was 309 nmol min-1 (mg protein)-1. For the S. peucetius enzyme, the K'm values for NAD+ and TDP-D-glucose were 20.1 microM and 34.7 microM, respectively. V'max values were 180 nmol min-1 (mg protein)-1 for NAD+ and 201 nmol min-1 (mg protein)-1 for TDP-D-glucose. TDP was a good inhibitor of TDP-D glucose 4,6-dehydratase from both organisms. The N-terminal amino acid sequence of the TDP-D-glucose 4,6-dehydratase from S. peucetius and from the erythromycin producer, Saccharopolyspora erythraea, were similar, whereas the enzyme from Streptomyces sp. C5 contained a different N-terminal amino acid sequence from either of the other two enzymes. PMID- 1588311 TI - Purification and characterization of pyruvate decarboxylase from Sarcina ventriculi. AB - Pyruvate decarboxylase from the obligate anaerobe Sarcina ventriculi was purified eightfold. The subunit Mr was 57,000 +/- 3000 as estimated from SDS-PAGE, and the native Mr estimated by gel filtration on a Superose 6 column was 240,000, indicating that the enzyme is a tetramer. The Mr values are comparable to those for pyruvate decarboxylase from Zymomonas mobilis and Saccharomyces cerevisiae, which are also tetrameric enzymes. The enzyme was oxygen stable, and had a pH optimum within the range 6.3-6.7. It displayed sigmoidal kinetics for pyruvate, with a S0.5 of 13 mM, kinetic properties also found for pyruvate decarboxylase from yeast and differing from the Michaelis-Menten kinetics of the enzyme from Z. mobilis. No activators were found. p-Chloromercuribenzoate inhibited activity and the inhibition was reversed by the addition of dithiothreitol, indicating that cysteine is important in the active site. The N-terminal amino acid sequence of pyruvate decarboxylase was more similar to the sequence of S. cerevisiae than Z. mobilis pyruvate decarboxylase. PMID- 1588312 TI - Control and location of acyl-hydrolysing phospholipase activity in pathogenic mycobacteria. AB - Phospholipase activities releasing fatty acyl moieties from phosphatidylcholine and phosphatidylethanolamine and lysophospholipase activity releasing fatty acid from lyso-phosphatidylcholine were detected in both Mycobacterium microti and Mycobacterium avium. Fatty acyl groups were released from both the 1- and 2 positions of phosphatidylcholine. Generally, phospholipase activities of M. avium were cryptic while phospholipase activities of M. microti were located on the bacterial surface. However, intact M. microti did not release fatty acids from phospholipids faster than M. avium. Neither Mycobacterium secreted acyl hydrolysing phospholipase activity. All phospholipase activities were stimulated by including phospholipids in growth media: generally, cell extracts contained 6- to 15-fold higher specific activities than extracts from mycobacteria grown in media without added phospholipid. However, not all phospholipase activities were stimulated to the same degree in any given set of conditions, suggesting the existence of more than one phospholipase gene in each Mycobacterium. PMID- 1588313 TI - Genome typing of southern African subgroup 1 geminiviruses. AB - The relatedness of subgroup 1 geminiviruses from a variety of naturally infected southern African graminaceous hosts was compared by DNA cross-hybridization, restriction endonuclease mapping and partial sequencing. Cross-hybridization divided the viruses into three groups: those closely related to maize streak virus (MSVs), and separate groups comprising a Panicum sp. virus (PanSV) and two sugarcane viruses (SSVs). Restriction mapping and comparisons, and phylogeny reconstructions from map data, showed that mapped and sequenced maize viruses were all highly similar; that two viruses of grasses and wheat bore limited resemblance to each other and to MSV, and that a mapped local and a sequenced Kenyan PanSV were similar, but that these and the two SSVs were dissimilar to each other and to all other subgroup 1 geminiviruses. The conclusions were: that maize viruses and the two viruses of wheat and grasses are probably strains of MSV; that two SSVs are only distantly related and distinct from MSVs; that the PanSVs are closely related to one another, but also distinct from other viruses; that all of the viruses in this study are part of a 'MSV-related sub-subgroup' of geminiviruses. Partial sequencing of cloned genomes reinforced conclusions drawn from other data, and indicated a definite relationship between the mapped and sequenced Panicum viruses. The implications of the results for taxonomic and epidemiological purposes are discussed. PMID- 1588314 TI - The nucleotide sequence of an infectious insect-transmissible clone of the geminivirus Panicum streak virus. AB - The infectious genome of a Kenyan isolate of Panicum streak virus (PSV) has been cloned and sequenced. Infection of host plants was done using an Agrobacterium binary vector containing a partial repeat of the genome. Progeny virus from resultant infections proved to be transmissible by the leafhopper Cicadulina mbila (Naude). Comparisons of the amino acid sequences of PSV DNA-encoded proteins with those of previously characterized geminiviruses infecting monocotyledonous plants, including maize streak virus, revealed high levels of identity. The evolutionary relationship between PSV and other geminiviruses infecting monocotyledons is discussed. PMID- 1588315 TI - The Anticarsia gemmatalis nuclear polyhedrosis virus polyhedrin gene region: sequence analysis, gene product and structural comparisons. AB - The genomic region of the Anticarsia gemmatalis multiple nucleocapsid nuclear polyhedrosis virus (AgMNPV) strain 2D encoding the polyhedrin gene was cloned and mapped, and a 2085 bp SphI-PstI fragment containing the gene was sequenced. The polyhedrin polypeptide of the parental isolate AgMNPV was manually sequenced, and the amino acid sequence obtained agreed with that deduced from the DNA coding region sequence. AgMNPV and Orgyia pseudotsugata MNPV (OpMNPV) are similar in terms of promoter structure and polyhedrin primary sequence, and the polyhedrin gene of both viruses is transcribed in the anti-clockwise direction in relation to their physical maps. The region upstream from the polyhedrin gene of AgMNPV, OpMNPV, Bombyx mori NPV and Autographa californica MNPV (AcMNPV) was compared and this showed that the open reading frame (ORF) common to all four viruses (ORF 5) has sequence homology with the AcMNPV 25K gene. The sequences between ORF 5 and the polyhedrin gene were found to be variable among the polyhedrin gene loci compared. Additionally, conserved elements in the promoters of the very late genes encoding polyhedrin and granulin, and those encoding two p10 proteins were found to share sequence homology and positional similarity with consensus regions in the conserved boxes A and C, responsible for binding transcription factors to eukaryotic 5S ribosomal RNA genes, and to box C of tRNA genes. PMID- 1588316 TI - Antigenic relationship and further characterization of two major Borna disease virus-specific proteins. AB - After immunization of mice with isolated Borna disease virus (BDV)-specific proteins having Mrs of 38/39K and 24K, monoclonal antibodies (MAbs) were obtained which were specific for one of the antigens in Western blot analysis. However, in immunoprecipitation assays it was found that some MAbs of each specificity reacted exclusively with their respective antigen from BDV-infected cells, whereas other MAbs coprecipitated the heterologous protein. The relationship between the 38/39K and 24K proteins was demonstrated by two-dimensional peptide mapping, which revealed four identical peptides. Additionally, it was found that neither the 38/39K nor the 24K protein is glycosylated, but that the 24K protein is phosphorylated at serine residues. Experiments employing various cell separation protocols revealed that the 38/39K and the 24K proteins are evenly distributed within infected cells; this was confirmed by immunofluorescence techniques using 38/39K- or 24K-specific MAbs. Iodination experiments clearly demonstrated that only the 38/39K protein is expressed on the surface of virus infected cells. PMID- 1588317 TI - Intracellular transport of rubella virus structural proteins expressed from cloned cDNA. AB - The structural proteins of rubella virus consist of a nucleocapsid protein (C) and two membrane-embedded spike glycoproteins (E1 and E2). Since many reports have suggested that rubella virus buds intracellularly, we have examined the intracellular transport of the structural proteins in the absence of virion formation, particularly whether the membrane glycoproteins are retained inside the cell or are transported to the cell surface. We have expressed the structural proteins from cloned cDNA either alone or in different combinations, have examined the intracellular location of the proteins by immunofluorescence and using biochemical methods, and have looked for plasma membrane-localized E1 or E2 using a cell surface biotinylation assay. The C protein was found in the Golgi complex when expressed with E2 and E1; without the membrane glycoproteins, C appeared to remain in the endoplasmic reticulum (ER). When expressed alone, E1 was retained in a pre-Golgi compartment, and was not detected at the cell surface in any cell line. When E2 was expressed alone a small fraction could be detected at the cell surface, but the majority was retained intracellularly, apparently in the ER and the Golgi. Both proteins were transported to the surface when they were expressed together, albeit with low efficiencies in all cell lines. These data suggest that, although neither glycoprotein carries a dominant intracellular retention signal, E2 and E1 are largely retained in the Golgi even when present as a transport-competent heterodimer. PMID- 1588318 TI - Isolation and identification of hepatitis E virus in Xinjiang, China. AB - This paper describes isolation and identification of a virus (termed strain 87A) which has the cytopathic effect and haemagglutination properties of hepatitis E virus (HEV). This virus was isolated by tissue culture from the faeces of a patient with acute non-A, non-B enteric hepatitis in Xinjiang, China. The isolated virus was neutralized by acute phase sera obtained from other patients with acute non-A, non-B enteric hepatitis. The virus particles also could be specifically aggregated with acute phase sera from patients with known HEV hepatitis in China, Burma, India and the U.S.S.R., and with acute and convalescent sera from an HEV-infected chimpanzee. Crystalline arrangements of virus particles in the cytoplasm were observed by electron microscopy in ultrathin sections of infected cells. The sedimentation coefficient of the strain 87A virus particles in sucrose gradients was 176S. Purified virus particles revealed a protein band of about 76K on SDS-PAGE and Western blotting. The evidence indicates that the strain 87A virus is an HEV. Our ability to propagate HEV in cell culture should facilitate research on this hepatotropic virus. PMID- 1588319 TI - Molecular epidemiology of rabies virus in France: comparison with vaccine strains. AB - A molecular epidemiological study of the rabies virus currently prevalent in France was carried out by directly sequencing polymerase chain reaction-amplified genes. The rabies virus pseudogene psi was chosen as the most divergent genomic area, and as such the best 'clock' for measuring virus evolution. Sequence comparisons between 12 wild rabies virus isolates indicated strong conservation whatever the host and wherever the virus had been isolated. This holds true for a unique wild reservoir, the fox. On the other hand, a good correlation between genetic and geographical criteria indicates a slow evolution of the wild virus in parallel with the spatio-temporal progression of the epizootic. In contrast to their intrinsic homogeneity (about 2% divergence), the wild isolate sequences showed a marked divergence from those of vaccine seed strains (about 14.7%). This finding invites world-wide molecular epidemiological studies, particularly in countries in which vaccination failures have been reported. PMID- 1588320 TI - Amino acid sequence identity between the HA1 of influenza A (H3N2) viruses grown in mammalian and primary chick kidney cells. AB - Primary isolation of type A influenza (H3N2) virus in mammalian Madin Darby canine kidney (MDCK) cells results in a virus with haemagglutinin (HA) identical to that of the virus replicating in the infected individual, whereas similar isolation of virus in the embryonated egg results in the selection of variants with amino acid substitutions in the globular head region of the HA molecule. To determine whether other mammalian and avian host cells routinely used in laboratory isolation of influenza viruses also impose a selective pressure on the replicating virus population, the HA of viruses isolated in several different primary or continuous mammalian cells or avian cells has been characterized. The HAs of H3N2 viruses isolated in monkey kidney LLC-MK2 and primary guinea-pig kidney cell culture were antigenically identical to MDCK cell-grown virus isolated from the same patient. The deduced amino acid sequence over the region of HA1 encoding residues implicated in host cell-mediated sequence variation revealed that the HA sequences of viruses isolated and passaged in these mammalian cell types, and in a human lung continuous cell line (MRC-5), were identical to that of the virus present in the infected individual. In addition, isolation of virus in avian primary chick kidney (CK) cells yielded a predominant virus with HA identical to that of mammalian cell-grown virus and the virus present in the original clinical material. However, passage of CK cell-grown virus in chicken embryos (eggs) resulted in the predominance of viruses with amino acid substitutions in HA, a minority of which resulted in antigenic variation. Since CK cell culture is used in the development of live attenuated influenza vaccines, the sequence identity between CK cell-grown virus and the virus present in the infected individual is reassuring. Nevertheless, subsequent passage of virus strains in eggs, necessary for vaccine production, must be monitored closely. PMID- 1588321 TI - Molecular characterization of phocine distemper virus: gene order and sequence of the gene encoding the attachment (H) protein. AB - Generation of a set of cDNA clones covering the N, P/V/C, M, F, H and part of the L gene of phocine distemper virus (PDV) has been described. The gene order of PDV determined from a physical as well as a transcriptional map, was identical to that of the other morbilliviruses so far studied. The H gene sequence (1951 nucleotides) contains one large open reading frame which encodes a protein of 607 amino acids, identical in length to that of the H protein of the Convac strain of canine distemper virus (CDV). Nucleotide and protein sequence comparisons between PDV and the other morbilliviruses provide further evidence in favour of PDV's inclusion in the morbillivirus genus as a distinct species closely related to CDV and more distantly to measles virus and rinderpest virus. PMID- 1588322 TI - The P gene of the porcine paramyxovirus LPMV encodes three possible polypeptides P, V and C: the P protein mRNA is edited. AB - The nucleotide sequence of the P gene of the porcine paramyxovirus La-Piedad Michoacan-Mexico virus (LPMV) was analysed. Three long open reading frames (ORFs) were found in the mRNA sense. Insertion of two G residues is necessary to obtain an ORF encoding the P protein, which gives a P protein of 404 amino acids with a calculated Mr of 42475. This form of editing was demonstrated, two non-templated G residues being added in a portion of the mRNA transcripts. The LPMV V protein, which has a conserved cysteine-rich C-terminal region, is encoded by an exact copy of the P gene. The third ORF has the capacity to encode a protein of 126 amino acids, which may resemble the C proteins found in some paramyxoviruses. The ORF starts from an AUG codon down-stream of the first AUG codon of the P/V ORF. PMID- 1588323 TI - Comparison of the amino acid sequences of nine different serotypes of hepatitis B surface antigen and genomic classification of the corresponding hepatitis B virus strains. AB - The surface (S) genes of 12 hepatitis B viruses (HBVs) encoding nine different serotypes of hepatitis B surface antigen (HBsAg) were amplified by the polymerase chain reaction and sequenced. These represented the eight strains of HBV, P1 to P8, defined at an international workshop on HBsAg subtypes in Paris in 1975, and the adrq- subtype. The S genes from additional HBV strains, one ayw4, one adw4 and one ayw1, of sub-Saharan African origin, were also sequenced. The relationship of these 12 new S gene sequences to those of the 20 published previously was investigated by constructing a phylogenetic tree, which confirmed a previous classification into four groups, designated A to D, based on 18 complete HBV genomes. When relating our sequenced S genes to these genomic groups, ayw1 of African origin and P6 (adw2) were both allocated to group A, the reference P1 (ayw1 of Vietnamese origin) was allocated to group B, P5 (ayr), P8 (adr) and adrq- were all related to group C, and P2 (ayw2) and P3 (ayw3) could both be allocated to group D. Interestingly, the S genes of w4 serotype viruses, i.e. P4 (ayw4) and P7 (adw4q-), differed by 4% or more from both previous groups and from each other, suggesting their classification into two new groups, for which the designations E and F are proposed. Genomes specifying ayw were also found in groups A and B; previously sequenced genomes specifying the ayw subtype have all been confined to group D. There were indications that the epitope for subdeterminants of w resided at amino acid positions 125 to 127. Thus, at positions 125 and 127, ayw1, ayw2 and adw2 had T and P residues, respectively, whereas M and T residues were at the corresponding positions of ayw3. Both ayw4 and adw4 had L at residue 127, and all strains expressing r, apart from P5, had an I instead of a T residue at position 126. PMID- 1588324 TI - Vaccinia virus gene SalF5R is non-essential for virus replication in vitro and in vivo. AB - A gene designated SalF5R from within the SalI F fragment of vaccinia virus strain WR has been characterized. The predicted primary translation product has 194 amino acids with an Mr of 22578 and has features typical of a class I membrane glycoprotein. At the amino and carboxy termini there are runs of hydrophobic residues that might function as membrane signal and anchor sequences, respectively, and after the C-terminal hydrophobic sequence there is a short charged sequence that may prevent passage of the molecule through the membrane. Between these hydrophobic regions there are two potential sites for addition of N linked carbohydrate. Northern blotting using a probe to an internal region of the open reading frame (ORF) detected an early transcript of 750 nucleotides and late transcripts of heterogeneous length. However, accurate mapping of the 5' ends of these transcripts did not reveal a monocistronic mRNA that might allow translation of the full-length SalF5R ORF. Instead two early transcripts were found, one beginning 130 nucleotides downstream of the start of the ORF, and a second initiating in the short intergenic region between SalF5R and SalF6R. The nearest late initiation site mapped to the beginning of the upstream gene SalF4R (profilin) and not the beginning of the SalF5R ORF. A virus deletion mutant lacking an internal 554 nucleotides of the 582 bp SalF5R ORF was constructed by insertion of the Escherichia coli guanine phosphoribosyl transferase gene linked to the vaccinia virus p7.5K promoter. The rate of replication and the final titre of intracellular naked virus produced by this virus was indistinguishable from wild-type virus in CV-1 and RK13 cells. In intranasally infected mice the virus lacking SalF5R was not attenuated in comparison to wild-type virus. The SalF5R site may be useful for insertion of foreign DNA into recombinant vaccinia viruses. PMID- 1588325 TI - Detection of RNA-protein complex in vaccinia virus core in vitro transcription system. AB - The incubation of vaccinia virus cores in appropriate conditions promotes the release of core proteins into a supernatant fraction. Under transcription assay conditions core mRNAs are extruded in association with viral core proteins, however the presence of these proteins within the core particle is not essential for RNA synthesis and extrusion. The RNA-protein complex is resistant to micrococcal nuclease. Five proteins of 60K, 43K, 28K, 18K and 14.5K with RNA binding abilities have been identified by [32P]RNA overlay protein blot assays. These proteins are likely to be a component of the viral ribonucleoprotein complex since core basic proteins with similar MrS have been identified and at least one RNA-binding protein is predicted in the vaccinia virus genome. PMID- 1588326 TI - Characterization of the discontinuities in rice tungro bacilliform virus DNA. AB - The dsDNA of rice tungro bacilliform virus (RTBV) has two discontinuities, one on each strand, each in a specific position as found in other pararetroviruses. The 5' end of discontinuity 1 was mapped to nucleotide 1 of the published RTBV DNA sequence which suggests that tRNAiMet serves as a primer for negative strand DNA synthesis. This 5' terminus contains up to two ribonucleotides and the 3' terminus overlaps it by five to 25 nucleotides. The discontinuity 2 (D2) did not map to a purine-rich region as has been found in other similar viruses. Both the 5' and 3' termini of D2 were heterogeneous in position giving structures varying from a gap of 10 nucleotides to an overlap of 103 nucleotides. PMID- 1588327 TI - The complete nucleotide sequence of RNA 1 of a German isolate of barley yellow mosaic virus and its comparison with a Japanese isolate. AB - The nucleotide sequence of RNA 1 of a German isolate of barley yellow mosaic virus has been determined and compared with a Japanese isolate of the same virus. The sequence identity is 93.6% at the nucleotide level and 96% at the amino acid level. Similar values have been found for the polyproteins of the RNA 2 of both isolates (95%). Both isolates show an RNA 1-encoded protein arrangement similar to that of potyviruses such as tobacco etch virus. In contrast, the polyproteins of the small RNAs (RNA 2) do not show such a similarity to the polyproteins of other potyviruses. However, there is a striking difference between the two isolates in the generally highly conserved active site of the RNA-dependent RNA polymerase. The German isolate exactly matches the consensus sequences for previously described potyviral RNA-dependent RNA polymerases, whereas the Japanese isolate does not. PMID- 1588328 TI - Complete nucleotide sequence of RNA 4 of rice stripe virus isolate T, and comparison with another isolate and with maize stripe virus. AB - The complete nucleotide sequence of RNA 4 of rice stripe virus isolate T (RSV-T) was determined and found to consist of 2157 nucleotides, containing two open reading frames (ORFs). One, deduced to be present in the 5'-proximal region of the viral-sense RNA, encodes the stripe disease-specific protein with Mr 20541, and the other ORF, in the 5'-proximal region of the viral complementary sense RNA, encodes an unknown protein with Mr 32474. Between these two ORFs there is an intergenic non-coding region that could form a secondary structure with two base paired hairpin configurations. These characteristics indicate that RSV-T RNA 4 has an ambisense coding strategy. Comparison of the two ORFs of RSV-T with those of another isolate revealed 97.2% and 98.0% identity for the nucleotide sequences, and 98.3% and 98.2% identity for the amino acid sequences. The leader sequences of these two isolates were the same. However, an insertion was found in the intergenic non-coding region of RSV-T. Furthermore, comparison of the nucleotide and amino acid sequences of RSV-T RNA 4 with those of RNA 4 of maize stripe virus, which is another member of the tenuivirus group, revealed greater identity, suggesting a close phylogenetic relationship between these two viruses. PMID- 1588329 TI - Evidence for translation of apple stem grooving capillovirus genomic RNA. AB - Apple stem grooving virus (ASGV) RNA was translated in a rabbit reticulocyte lysate system and shown to direct the synthesis of several polypeptides of Mr ranging from 200K to 43K. A polypeptide of 200K was a major product, but no polypeptide with electrophoretic mobility the same as that of the ASGV coat protein was synthesized. Immunoprecipitation experiments showed that a polypeptide of 200K was selectively precipitated by antiserum against purified ASGV. These results indicate that ASGV coat protein is translated as part of a 200K polyprotein. PMID- 1588330 TI - A comparison, using dsRNA analysis, between beet soil-borne virus and some other tubular viruses isolated from sugar beet. AB - Double-stranded RNA preparations from Chenopodium quinoa leaves inoculated with two English isolates of beet soil-borne virus (BSBV), BSBV-N and BSBV-452N, a French isolate of beet necrotic yellow vein virus (BNYVV), a Swedish isolate of a tubular beet virus (86-109) or a Belgian isolate of a similar virus (1530) were compared following separation on non-denaturing polyacrylamide gels. The dsRNAs of BNYVV differed in mobility from those isolated from tissue infected with the other four tubular beet viruses, which possessed three major dsRNA species. The degree of sequence identity between BNYVV, BSBV-N, 86-109 and 1530 was investigated by RNA-RNA blot hybridization using 32P-5' end-labelled probes. Reciprocal hybridization experiments revealed similarity between the BSBV-N, 86 109 and 1530 isolates, but none between these isolates and BNYVV. PMID- 1588332 TI - Vulnerability to substance abuse and psychopathology among siblings of opioid abusers. AB - Vulnerability to drug abuse and psychopathology was explored among siblings of 201 opioid-addicted probands. Disorders were evaluated based on family histories among 476 siblings; a subset of 133 siblings was also directly interviewed. Results indicated that a) siblings of opiate addicts had substantially higher rates of several disorders in comparison with rates in the community; b) as compared with parents of addicts, siblings had elevated rates of substance abuse and antisocial personality; c) the presence of a major psychiatric disorder significantly increased the risk of developing substance abuse among siblings; and d) psychopathology appeared to precede drug abuse in terms of age of onset in this group. Results obtained with the interviewed sample of siblings were replicated in the overall group. Findings of the study are discussed in terms of implications for the classification and treatment of substance abuse. PMID- 1588331 TI - Using vulnerability indicators to compare conceptual models of genetic heterogeneity in schizophrenia. AB - The search for indicators of vulnerability has been important in schizophrenia research, but, as in many areas, progress has been impeded due to the heterogeneity of schizophrenic disorders. How one conceptualizes the observed heterogeneity is dependent upon the particular genetic model to which one subscribes. In this article, we delineate several models that may account for the distributions of vulnerability indicators in groups of schizophrenic patients and their ill and well relatives. We present these models for heuristic purposes so that they may serve to guide the interpretation of data with respect to the issue of teasing apart familial and nonfamilial environmental components of putative vulnerability indicators. It is suggested that investigators will profit by: a) efforts to combine psychiatric genetic paradigms in order to maximize the yield of family study data, and b) thinking in terms of comparing the ability of different models to account for research findings. PMID- 1588333 TI - An examination of the relationships among three outcome scales in schizophrenia. AB - The functioning of 94 schizophrenic subjects was rated using the Global Assessment Scale, the Strauss and Carpenter Outcome Scale, and the Role Functioning Scale. The convergent validity among the scales was quite modest and highly variable. Solid empirical convergence only occurred when two of the scales each measured social and vocational dimensions of functioning. It is argued that these findings strongly illustrate the need for conceptual and operational consensus in this area. The findings also support the notion of outcome in schizophrenia as a set of distinct, yet linked, dimensions. Other implications of the findings for the definition and measurement of outcome in schizophrenia when using global and multidimensional scales are discussed. PMID- 1588334 TI - Lipreading in patients with schizophrenia. AB - This study was designed to explore whether schizophrenic patients who are able to maintain their gaze with adequate persistence could competently lip-read. Four lipreading tests, designed to assess recognition of syllables, words, and overlearned sentences, were administered to 15 schizophrenic and 15 normal subjects matched for age, sex, and educational level. The patients proved to be competent lip-readers susceptible to the blend illusion and were inferior only in lipreading of overlearned sentences. The latter difficulty may tentatively be attributed to the inadequacy of the patient's premorbid social network for establishing contextual cues that aid in the recognition of overlearned sentences. PMID- 1588335 TI - Age and impaired subjective support. Predictors of depressive symptoms at one year follow-up. AB - We followed a cohort of subjects (predominantly inpatients) suffering a major depressive episode in midlife and late-life for 1 year (N = 118). In this follow up study, we examined three hypotheses. a) Elder subjects suffering major depression, compared with middle-aged subjects, will more likely report endogenous symptoms and less likely report decreased life satisfaction symptoms at 1-year follow-up. b) Impaired social support during the index episode will predict poor life satisfaction, but not endogenous symptoms at 1-year follow-up, regardless of age. c) Impaired social support during the index episode will be more predictive of decreased life satisfaction symptoms in midlife, compared with late life, at 12-month follow-up. The first two hypotheses were not supported, but the third hypothesis was. Both decreased life satisfaction and endogenous symptoms at outcome were significantly predicted by impaired social support during the index episode. Impaired social support predicted a poor outcome from an episode of major depression in both middle life and late life in controlled analyses. However, the effect of impaired subjective social support was conditional on age. Subjective social support appears to have a decreasing influence on the report of both endogenous and decreased life satisfaction symptoms for older individuals. PMID- 1588336 TI - Coping in panic and major depressive disorder. Relative effects of symptom severity and diagnostic comorbidity. AB - This study used the Ways of Coping Checklist to examine coping style in patients with panic and major depressive disorders. The relative contribution of distress (symptom severity) and diagnostic comorbidity was determined in three sets of diagnostic subgroups: patients suffering from both panic and major depressive disorders (compared with either disorder alone); panic patients with and without agoraphobia (regardless of concurrent depression); and patients with versus without a concurrent axis II personality disorder. Use of less problem-focused and more emotion-focused coping was strongly correlated with level of distress and was associated with all three examples of diagnostic comorbidity when level of distress was used as a covariate. Regression analyses showed that, except for the presence of a personality disorder, distress was a much stronger predictor of coping than diagnostic subtype. PMID- 1588337 TI - Civil commitment and arrests. An investigation of the criminalization thesis. AB - This study examined one part of the criminalization thesis, which holds that the dangerousness standard of reform civil commitment law has led to the frequent arrest of mentally ill persons. It followed a large statewide sample of civil commitment candidates for 6 months through arrest records to observe their number and type of arrests. It found that: ex-candidates were seldom arrested; over half of arrests were accounted for by a few with multiple arrests; the nonviolent and those released were no more likely to be arrested than the violent and those committed; and charges were more often for the less serious offenses, but not predominantly for nuisance offenses [corrected]. PMID- 1588338 TI - Family process and hypnotic susceptibility. A preliminary investigation. AB - Prior research has found an association between severe punishment during childhood and adult hypnotic susceptibility. The present study investigated family process variables that potentially underlie this association. Two hundred and five college students completed a self-report family process measure and participated in a group hypnotic induction procedure. A subsample of 128 students rated severity and consistency of the punishment they received as children. Subjects with high hypnotic ability reported significantly higher family cohesion than did subjects of low hypnotic ability. A significant linear relation between family cohesion and hypnotizability was also found. Unexpectedly, punishment severity and consistency did not relate to hypnotic susceptibility. Potential causal mechanisms between family process variables and hypnotizability are discussed. PMID- 1588339 TI - More data on the Addiction Severity Index. Reliability and validity with the mentally ill substance abuser. AB - The Addiction Severity Index (ASI) is a semistructured interview that collects data from substance abusers in seven problem areas: medical, employment, legal, alcohol, other drug use, family-social functioning, and psychological status. In each area, the clients provide an estimate of the seriousness of the problem and their need for treatment. It has been demonstrated in a number of studies to be reliable, valid, and useful in monitoring treatment changes and in matching substance-abusing clients to treatments. This study investigates the usefulness of the ASI with male and female substance abusers who suffer a concurrent major psychiatric disorder (N = 152). Data on the independence of the problem scales, their internal consistency, interrater reliability, and concurrent validity are presented. It is concluded that: a) the problem areas are independent from each other, underscoring the need for multidimensional assessment; b) interviewer severity ratings provide information in addition to that provided by clients; c) the reliability of the composite scores is generally adequate, with the exception of the legal and family-social scales; and d) further examination of the employment scores is required. PMID- 1588340 TI - Fluoxetine treatment of depression in mentally retarded adults. AB - Six depressed mentally retarded adults were treated with fluoxetine in an open trial. Five patients significantly improved, and one patient partially improved, after treatment with fluoxetine. Their mean Hamilton Depression Rating Scale score was significantly reduced after treatment. These results suggest that fluoxetine is a safe and effective treatment for depression in mental retardation. Some potential advantages of using fluoxetine in this clinical population are discussed. Additional controlled research studies are needed to confirm these findings. PMID- 1588341 TI - Atypical unipolar depression in mentally retarded patients: amoxapine treatment. PMID- 1588342 TI - Deviant sexual responsiveness on penile plethysmography using visual stimuli: alleged child molesters vs. normal control subjects. PMID- 1588343 TI - Complexation studies on inositol-phosphates: IV. Ca(II) complexes of myo-inositol 1,4,5-trisphosphate. AB - The stability constants of the complexes formed between Ca2+ and the myo-inositol 1,4,5-triphosphate (Ins(1,4,5)P3) were determined by potentiometric titration in two different media and temperature conditions (medium 1: I = 0.1 M But4NBr, 25 degrees C; medium 2: I = 0.2 M KCl, 37 degrees C). Mainly because of the presence of potassium the results obtained in these media show large differences in both the nature and the stability of the complexes. In medium 1, MH2L and M2L species are formed along with the ML and MHL species which also exist in medium 2. In addition, the stability of the latter species decreases by more than one log unit in going from medium 1 to medium 2. In an attempt to assess the biological significance of the metal binding to Ins(1,4,5)P3, the results were compared to the Ca2+-ATP complexes that form in the same media conditions. Taking into account the relative stability of the complexes of both systems, it is likely that the action or metabolism of Ins(1,4,5)P3 may be influenced by coordination of either alkali or alkali-earth cations. PMID- 1588344 TI - A comparative study of pH/activity profiles for the anaerobic H2O2 and alkyl hydroperoxide supported N demethylation of N methylaniline catalyzed by alkaline haematin and microsomal cytochrome P-450. AB - A comparative study of the effect of pH on haemin-mediated H2O2 and alkyl hydroperoxide-supported N-demethylation of N-methylaniline and the corresponding cytochrome P-450 mediated process has been carried out. This extends previous studies and provides quantitative evidence that the same active oxygen species are involved in both the enzymic and metalloporphyrin mediated processes. Furthermore, this evidence clearly indicates that the environment at the point of catalysis in the enzyme active site differs considerably from that of the bulk solution. PMID- 1588345 TI - A role for microglia in the maintenance of photoreceptors in retinal transplants lacking pigment epithelium. AB - Studies on intact retina have pointed to a necessary role for retinal pigment epithelium in the maintenance of photoreceptor outer segments and for regeneration of visual pigment. However, it has been shown that when embryonic retinae are separated from the pigment epithelium and transplanted into the brain of neonatal rats, the transplanted photoreceptors develop outer segments and the retina responds to light in the apparent absence of pigment epithelial cells. We confirm that there are no retinal pigment epithelium cells associated with transplanted retinae in the present series of experiments and show that a row of cells, composed predominantly of microglia of host origin, border the graft. These cells can be seen to contain engulfed outer segments when they are apposed to the outer retina, suggesting that the microglia have assumed, at the least, the phagocytic function normally associated with retinal pigment epithelium. Microglial cells and their processes are also found within the transplant, but these cells are typically devoid of phagosomes, indicating an absence of phagocytic activity. The close physical association of these resting microglia with the transplant may facilitate their role in antigen presentation under specific conditions of immune provocation. PMID- 1588346 TI - Fine structure of the blood-brain interface in the cuttlefish Sepia officinalis (Mollusca, Cephalopoda). AB - The blood-brain interface was studied in a cephalopod mollusc, the cuttlefish Sepia officinalis, by thin-section electron microscopy. Layers lining blood vessels in the optic and vertical lobes of the brain, counting from lumen outwards, include a layer of endothelial cells and associated basal lamina, a layer of pericytes and a second basal lamina, and perivascular glial cells. The distinction between endothelial cells and pericytes breaks down in small vessels. In the smallest microvessels, equivalent to capillaries, and in venous channels, and endothelial and pericyte layers are discontinuous, but a layer of glial cells is always interposed between blood and neural tissue, except where neurosecretory endings reach the second basal lamina. In microvessels in which cell membranes of the entire perivascular glial sheath could be followed, the glial layer was apparently 'seamless', not interrupted by an intercellular cleft, in ca 90% (27/30) of the profiles. Where a cleft did occur, it showed an elongated overlap zone between adjacent cells. The walls of venous channels are formed by lamellae of overlapping glial processes. In arterial vessels, the pericyte layer is thicker and more complete, with characteristic sinuous intercellular clefts. Arterioles are defined as vessels containing 'myofilaments' within pericytes, and arteries those in which the region of the second basal lamina is additionally expanded into a wide collagenous zone containing fibroblast-like cells and cell processes enclosing myofilaments. The 'glio-vascular channels' observed in Octopus brain are not a prominent feature of Sepia optic and vertical lobe. The organization of cell layers at the Sepia blood-brain interface suggests that it is designed to restrict permeability between blood and brain. PMID- 1588347 TI - Electron-dense tracer evidence for a blood-brain barrier in the cuttlefish Sepia officinalis. AB - Electron-dense tracers were used to study the permeability of the blood-brain interface in a cephalopod mollusc, the cuttlefish Sepia officinalis. Gel filtration established that horseradish peroxidase is a suitable tracer for in vivo injection, but microperoxidase is not, being subject to binding by plasma proteins. Perfusion-fixed brain vertical and optic lobes showed no endogenous peroxidatic activity. Horseradish peroxidase was injected intravenously, and allowed to circulate for 10-35 min before tissue fixation by immersion or perfusion. Horseradish peroxidase reaction product was undetectable in the bulk of the brain parenchyma. In microvessels, venous vessels and at the brain surface, horseradish peroxidase penetrated the layers of endothelial and pericyte cells, being stopped by the layer of perivascular glia. In arterial vessels, tracer restriction occurred at the level of the pericytes. In the region of tracer blockade, a gradient of tracer could be traced in the intercellular cleft, from high at the luminal end to undetectable at the tissue end. The clefts of the restricting zone were generally wide (15-20 nm), with faint periodicities or linking structures spanning the cleft, and contained a fibrillar extracellular material. Perfusion of lanthanum chloride in saline for 15 min, followed by precipitation of lanthanum phosphate during fixation, resulted in lanthanum tracer distribution similar to that of horseradish peroxidase. Horseradish peroxidase was seen filling extracellular spaces within the neuropile when the blood-brain barrier was breached by a stab wound, indicating that the interstitium itself does not restrict tracer diffusion. It is concluded that Sepia has a blood-brain barrier tight to horseradish peroxidase and ionic lanthanum. The restricting junction is not a typical zonula occludens or septate junction, but appears to reduce tracer penetration by a filtering mechanism within the extracellular cleft. The barrier is formed by perivascular glial cell processes in the microvessels and venous vessels, but by pericytes in arterial vessels. This organization suggests that a glial blood-brain barrier may be the primitive condition, and a barrier associated with vascular elements (endothelium/pericyte) a later development. PMID- 1588348 TI - Freeze-fracture evidence for a novel restricting junction at the blood-brain barrier of the cuttlefish Sepia officinalis. AB - The blood-brain barrier in the cuttlefish Sepia officinalis has been studied with the freeze-fracture technique. Previous thin-section electron microscopy showed that a restricting junction is formed between perivascular glial processes in microvessels and venous vessels, and between pericytes in arterial vessels; the restriction appeared not to be a classical zonula occludens or septate junction. In freeze-fracture replicas from brain optic and vertical lobe, endothelial cells, pericytes and perivascular glia could be recognized by their morphology and relation to the vascular lumen. In microvessels, endothelial and pericyte membranes showed sparse but uniform distribution of P-face intramembranous particles, with no particular particle aggregations. Perivascular glial membranes had a higher density of intramembranous particles but again no particle alignments characteristic of known restricting junctions were seen, although clusterings of intramembranous particles resembling gap junctions were present. In larger venous vessels, the perivascular glial layer showed a multilamellated organization, but again no arrays of intramembranous particles were detected, although this should be a favourable site for visualization of the restricting junctions. The walls of arterial vessels showed collagen deposits and cell processes with apparent intracellular myofilamentous profiles, but no intramembranous junctional particle arrays. It is concluded that the junctional zone observed in thin section electron microscopy is not associated with aligned aggregations of intramembranous particles detectable in freeze-fracture replicas, strengthening the evidence that this is a novel type of restricting junction. PMID- 1588349 TI - A fibre matrix model for the restricting junction of the blood-brain barrier in a cephalopod mollusc: implications for capillary and epithelial permeability. AB - A model is proposed for the novel restricting junction forming the blood-brain barrier in a cephalopod mollusc, the cuttlefish Sepia officinalis. The model is based on electron-microscopic findings, from both thin-section and freeze fracture material, the distribution of electron-dense tracers, and radioisotopic measurements of permeability using small non-electrolytes. Biochemical properties of Sepia plasma proteins are also considered. It is proposed that an effective blood-brain barrier is achieved by a combination of mechanisms. As much as 90% of the Sepia brain microvessel wall is covered by a 'seamless' glial sheath, without intercellular clefts, limiting the number of potential leakage sites. The remaining clefts follow a tortuous course increasing the diffusion path to the neuropile. Entry into the clefts is reduced by a restricting junctional region at the luminal end, characterized by delicate striations spanning the cleft, and forming an effective barrier to both horseradish peroxidase and ionic lanthanum. This is a novel junctional type, different from previously-described vertebrate and invertebrate occluding junctions. It is proposed that the junction acts as a fine-mesh molecular filter, with condensed extracellular material in the cleft, cross-linked and consolidated by bound plasma protein. Cephalopod haemocyanin or its subcomponents are considered likely candidates for the bound protein. The model predicts that blood-brain barrier permeability should be sensitive to the charge structure of the extracellular matrix and the presence of protein, and is analogous to the 'fibre matrix' model of vertebrate capillary permeability. The Sepia blood-brain barrier also highlights the different strategies available for constructing a restricting cell layer, and suggests a possible evolutionary pattern underlying the present range of junctional mechanisms in vertebrate and invertebrate epithelia. PMID- 1588350 TI - Does physical activity lower blood pressure: a critical review of the clinical trials. AB - This review critically appraises 22 recent articles of trials of physical activity, as a means of reducing blood pressure. The quality of the literature remains poor and of the 13 controlled trials of habitual activity only one did not have a major design fault. Overall, blood pressure was reduced by physical activity in both hypertensive and normotensive persons. This effect was independent of weight loss and in some studies blood pressure reduction occurred in the presence of weight gain. The average reduction in the better designed studies was approximately 6-7 mmHg for both systolic and diastolic blood pressure which compares favourably with studies of pharmacological treatment. The better designed studies reported smaller reductions than studies with poorer design. All activities, including circuit weight training, lowered blood pressure and daily activity produced greater blood pressure reduction than when performed three times per week. It is concluded that physical activity has an independent capacity to lower blood pressure. PMID- 1588351 TI - Breast cancer detection in relation to oral contraception. AB - Analyses of tumor size and breast cancer stage were used to determine whether biased detection of breast cancer could have materially influenced estimates of risk associated with use of oral contraceptives. In a population-based case control study conducted from 1980-1982, surveillance for breast cancer by breast exams, but not mammography, was found to be strongly linked to use of oral contraceptives. Tumors were slightly smaller and less likely to be late-stage (TNM stage III or IV) in patients who had used oral contraceptives. The net effect of any diagnostic bias on advancing the date of cancer diagnosis, whether from breast exams or other sources, was estimated to be less than 8 weeks. This corresponds to spuriously increasing the risk of early-occurring breast cancer in oral contraceptive users by at most 2.4% (relative risk = 1.024). PMID- 1588352 TI - A scale for the measurement of quality of life in adults with asthma. AB - A 20-item self-administered questionnaire with Likert scale responses was developed to measure quality of life in adult subjects with asthma. A total scale score together with subscale scores for breathlessness, mood disturbance, social disruption and concerns for health were calculated by addition of item scores. Items for the scale were selected by principal components analysis of the responses of 283 subjects to a preliminary pool of 69 items. In 58 subjects with stable asthma, good short term test-retest reliability was demonstrated with the intraclass correlation coefficient for the total scale being 0.80. The questionnaire was internally consistent in a sample of outpatients (Cronbach's alpha 0.92 in 77 subjects) and in a community sample with asthma (Cronbach's alpha 0.94 in 87 subjects). Weak correlations in the expected direction were seen with three medical markers of asthma severity. This supports the construct validity of the questionnaire and emphasizes that quality of life represents a separate dimension of asthma. PMID- 1588353 TI - Exploring the influence of multiple variables on the relationship of age to quality of life in women with breast cancer. AB - This paper explores the relationship between age, psychosocial status and quality of life in a community based sample (n = 229) of newly-diagnosed breast cancer patients. A casement display methodology is used to examine the influence of demographic and medical variables on the outcome variables of interest (psychosocial status and quality of life) and their relationship to age. Based on the literature, a positive relationship between age and psychosocial status was predicted, but the relationship between age and quality of life was uncertain. For the whole sample, a weakly positive relationship between age and measures of psychosocial status and quality of life was observed. In the exploratory studies using the casement plots, the positive relationship between age and quality of life was most strong and significant in married women and in women who had received segmental mastectomy. Among sub-groups examined according to marital status and type of surgery, a positive relationship between age, psychosocial status and quality of life was observed only in married women who received segmental mastectomy. Additional preliminary observations were made about the relationship of household income and age to the outcome variables being studied. The casement plot methodology permits the simultaneous evaluation of multiple variables as a preliminary step before hypothesis development and should be considered when complex clinical problems are being evaluated. PMID- 1588354 TI - Health response by questionnaire in arsenic-exposed populations. AB - The health status of populations exposed to arsenic through drinking water was determined by a mailed questionnaire. Participants were selected from three communities located in Nevada with 1977 tap water arsenic levels of approximately 0.1 mg/l and one California community with 1977 levels around 0.39 mg/l. The questionnaire responses were obtained in 1979 from the four exposed communities and compared to those of a Wyoming community whose tap water levels of arsenic were less than 0.001 mg/l in 1979. No difference in health status for gastrointestinal, neurological, musculoskeletal, circulatory and skin disorders was found. The average number of years of consumption given by length of residence was 6-16 years. We conclude that the health status of these arsenic exposed populations has not been adversely affected. PMID- 1588355 TI - Application of a stopping rule based on total treatment failures: the postoperative Crohn's disease trial. AB - The Postoperative Crohn's Disease Trial (PCDT), a placebo-controlled randomized trial of Rowasa I in the prevention of postoperative recurrence of Crohn's disease, is used as an example of how a stopping rule based on total endpoint occurrences can provide considerable advantage over standard fixed sample size methods. It can be used when the primary outcome is occurrence or time to occurrence and does not raise the troublesome issues regarding the unblinding of group differences that other sequential methods create. The main advantage of the total endpoint stopping rule is that it provides set power. Standard fixed sample size designs provide a given power only on average. The power actually achieved in a particular fixed sample size trial is largely determined by the overall observed rate of endpoint occurrences. This claim about the total endpoint stopping rule is well established in the statistical literature and, as well as outlining the mathematical details in an Appendix, we use computer simulation of the PCDT to demonstrate that use of the stopping rule will allow termination of the trial while maintaining power and type I error at a predetermined level. PMID- 1588356 TI - Variability among methods to assess patients' well-being and consequent effect on a cost-effectiveness analysis. AB - Cost-effectiveness analysis is emerging as an approach for determining the relative value of health care programs, technologic innovations, and clinical decisions. Increasingly, patients' stated values for quality of life are applied as adjustment in these analyses; the results may vary depending on how individuals assess their well-being. We interviewed 58 patients with chronic renal failure to determine the level of agreement among six methods for assessing well-being, and to determine the effects of variation in assessed well-being on the results of a cost-effectiveness analysis of in-center hemodialysis. Patients reported well-being using the Sickness Impact Profile, Campbell Index of Well being, Kaplan-Bush Index of Well-being, categorical scaling, standard gamble, and time trade-off. We found that patient well-being was substantially higher as evaluated by the Sickness Impact Profile compared to the other five methods. The Sickness Impact Profile and the Kaplan-Bush Index of Well-being provided much narrower distributions of assessed values relative to other measures. Correlations among assessment methods were poor (Spearman rank-correlation coefficients range: 0.094-0.519). Discrepancies among indices were particularly vivid when we evaluated data at the individual level; many patients reported a high level of well-being according to one index and a low level of well-being according to a different index. The cost effectiveness of in-center hemodialysis varied from $34,893 to $45,254 per quality-adjusted life-year saved according to the Sickness Impact Profile and standard-gamble technique respectively. The substantial variability in patients' stated quality of life may preclude the use of a single method to analyze the cost effectiveness of a health program. PMID- 1588357 TI - Height, infant-feeding practices and cardiovascular functioning among 3 or 4 year old children in three ethnic groups. AB - Barker recently hypothesized that factors affecting prenatal and infant growth are related to adult blood pressure and CVD mortality. Predictions from Barker's hypothesis in regard to infant feeding were tested among a sample of 3 or 4 year old children. The relationship of infant-feeding characteristics (duration of breast-feeding, times of introduction of high fat, high carbohydrate, high potassium foods and table salt) to indicators of cardiovascular functioning (resting blood pressures and heart rates, and heart rate response to graded activity) while controlling for anthropometric (height, sum of seven skinfolds, BMI) and demographic (ethnicity, gender, social status) characteristics revealed that infant-feeding practices were not related to CV functioning in the predicted directions among this sample of 3 or 4 year old children. Furthermore, the positive relationship between height and systolic blood pressure was inconsistent with the Barker hypothesis. PMID- 1588358 TI - Lower extremity arterial disease and the aging process: a review. AB - Atherosclerotic disease is a major health problem in the elderly population in the U.S. To date, most research has focused on the coronary and cerebral manifestations of the disease. Lower extremity arterial disease (LEAD) has received less attention. However, the use of simple objective non-invasive diagnostic techniques in recent population-based studies has allowed identification of asymptomatic LEAD and shown that the prevalence of disease is several fold higher than previously estimated. The prevalence increases sharply with age, from 3% in those under 60 years to over 20% at 75+ years. Detection of LEAD in the elderly provides a rapid, easy assessment of the level of atherosclerosis in the body and identifies those at high risk for mortality and morbidity. LEAD is associated with a relative risk of 4 to 5 for all cause mortality. In about 25% of those with LEAD, the disease progresses over time, leading to loss of mobility, gangrene or amputation. This review summarizes current knowledge regarding the etiology and natural history of LEAD from an epidemiologic viewpoint, delineating areas in which additional research is needed. PMID- 1588359 TI - Non-differential underestimation may cause a threshold effect of exposure to appear as a dose-response relationship. AB - It is generally believed that non-differential misclassification will lead to a bias toward the null-value. However, using one graphical and one numerical example, we show that in situations where underestimation more than overestimation is the problem, non-differential misclassification may lead to a bias away from the null-value for intermediate categories of exposure variables. We show that a true threshold level for an exposure may, subsequently, appear as a dose-response relationship. Underestimation more than overestimation is likely to occur in studies in which self-reports are used to obtain data on activities which respondents voluntarily engage in and which are socially not acceptable or known to be potentially dangerous. Researchers should be aware that both a shown deleterious effect at a low level of exposure and a dose-response relationship may in fact be spurious and due to underestimation of exposure at higher levels. PMID- 1588360 TI - Assessment of sun sensitivity by questionnaire: validity of items and formulation of a prediction rule. AB - Sun sensitivity is a major risk factor for melanoma, basal cell carcinoma, and squamous cell carcinoma of the skin. Several variables have been used in epidemiologic studies to measure sun sensitivity. The present study assesses their validity and combines them to form a prediction rule for an objective measure of sun sensitivity, the minimal erythema dose of ultraviolet B radiation required to produce visibility reddened skin (MED). Participants were 116 patients with psoriasis presenting for phototherapy who completed a sun sensitivity questionnaire. Of the 14 questionnaire items evaluated, 10 were associated with the MED beyond expectation based on chance. The closest association was with the skin type (of Fitzpatrick), a 4-point scale based on historical ability to tan and susceptibility to sunburn. Color of untanned skin and hair were also independent predictors, and were included in the final prediction rule, which correlated 0.55 with MED. Combining items yields a more accurate predictor of sun sensitivity than any one or two individual response variables, and hence may be preferable for epidemiologic studies. PMID- 1588361 TI - The validity of estimating heart disease reduction from a Framingham logistic equation. AB - We compared two ways in which a logistic equation could be used to estimate the number of heart disease events prevented after lowering blood cholesterol levels. Men were selected from an Australian population survey who met the entry criteria of the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT). The numbers of heart disease events expected over 7.4 years were calculated from the logistic equation after reducing the men's blood cholesterol by the amounts achieved in the LRC-CPPT placebo and treatment groups (our simulated placebo and treatment groups). The number of events prevented was calculated as the absolute difference between the simulated groups (9.48 per 1000 men per 7.4 years) and the percentage difference of the simulated groups multiplied by the observed incidence rate in the LRC-CPPT placebo group (13.66 per 1000 men per 7.4 years). The second estimate was closer to that observed in the LRC-CPPT (17.10 per 1000 men per 7.4 years), and we recommend this approach in cost-effectiveness studies. PMID- 1588362 TI - Fibrinogen: the plot thickens. PMID- 1588363 TI - No free lunch. PMID- 1588364 TI - Intrapleural cisplatin and mitomycin for malignant mesothelioma following pleurectomy: pharmacokinetic studies. AB - PURPOSE: Intrapleural cisplatin-based chemotherapy has been used in the treatment of patients with malignant pleural mesothelioma and malignant pleural effusions, but the pharmacokinetics of this form of chemotherapy have not been previously evaluated. We performed pharmacokinetic studies on 12 patients who received both intrapleural cisplatin and mitomycin immediately following pleurectomy/decortication for malignant pleural mesothelioma. PATIENTS AND METHODS: Simultaneous pleural fluid and plasma samples were collected at 15 and 30 minutes, and at 1, 2, 3, 4, and 24 hours after administration of the intrapleural chemotherapy (cisplatin 100 mg/m2 and mitomycin 8 mg/m2), and after cisplatin (total and free) and mitomycin levels were measured. The mean peak levels, the areas under the concentration-time curve (AUC) and the drug half lives (t1/2s) in plasma and pleural fluid were compared using the paired t test. Differences were considered significant if P less than or equal to .05. RESULTS: Systemic absorption was rapid, with peak plasma levels being reached within 1 hour of administration of the intrapleural chemotherapy. Peak plasma levels measured after intrapleural chemotherapy approximated those reportedly attained during systemic administration of these drugs at similar doses. However, the mean peak cisplatin and mitomycin levels, and their mean AUCs, were significantly higher in the pleural fluid than in the plasma. There was a three- to fivefold advantage (on a logarithmic scale) for pleural to plasma AUCs for both cisplatin and mitomycin. The mean t1/2s for cisplatin and mitomycin were significantly longer in the plasma than in the pleural fluid. CONCLUSIONS: The pharmacokinetics of intrapleural cisplatin-based chemotherapy are analogous to those of intraperitoneal chemotherapy. Our findings show that intrapleural cisplatin-based chemotherapy has a distinct local pharmacologic advantage, but also produces significant and sustained drug plasma levels. PMID- 1588365 TI - Patient compliance with oral chemotherapy as assessed by a novel electronic technique. AB - PURPOSE: Previous reports have suggested low rates of compliance with the oral component of cancer chemotherapy, which, if confirmed, would have serious implications on treatment. Because of the uncertainties in the methodology used in previous studies, we have assessed compliance with a novel technique. PATIENTS AND METHODS: An "intelligent" tablet bottle was used, which, unknown to the patient, electronically records the times of opening over a period of weeks. The records were scored for overall compliance (total number of bottle openings as a percentage of the prescribed number) and for daily and hourly irregularity indices. Twenty-one patients undergoing treatment for Hodgkin's or non-Hodgkin's lymphoma were monitored for a total of 65 treatment periods, each of up to 2 weeks (852 days in total). Eight measures of side effects and quality of life were self-assessed daily by the patients using a diary card. RESULTS: The overall compliance was 100.6% +/- 20.6% (mean +/- SD). Overall compliance was lower (mean reduction, 10%) in treatment periods with drugs prescribed to be taken three times a day. It was not possible to demonstrate convincingly any relationship between compliance and any of the following: drug type, monitoring period sequence, the diary card scores of side effects and quality of life, number of relapses, and time since initial diagnosis. CONCLUSION: These results are reassuring, but further work is in progress to measure compliance in other treatment regimens in which the side effects are more severe and the prognosis is worse. PMID- 1588366 TI - Inflammatory breast cancer: a review. AB - PURPOSE: The natural history of inflammatory breast cancer and the recent advances in its management were reviewed. DESIGN: The English medical literature from 1924 to 1990 was reviewed using the Cancerline and Medline retrieval systems, and through a manual review of bibliographies of identified articles. RESULTS: The majority of patients with inflammatory breast cancer treated only with local therapies died 18 to 24 months after diagnosis. A combined modality approach with chemotherapy, surgery, and radiation therapy has improved disease free and overall survival rates for inflammatory breast cancer. Approximately 35% to 55% of patients treated with combined modality regimens remain disease-free and alive at 5 years. CONCLUSION: Induction combination chemotherapy administered with radiation therapy, mastectomy, both, or with additional chemotherapy favorably alters the natural history of inflammatory breast cancer. New drug combinations and high-dose chemotherapy with autologous bone marrow support are being evaluated to improve further patient survival. PMID- 1588367 TI - Breast cancer: evaluating trial results. PMID- 1588368 TI - Suramin awakes? PMID- 1588369 TI - Meta-analyses need new publication standards. PMID- 1588370 TI - Expectancy or primary chemotherapy in patients with advanced asymptomatic colorectal cancer: a randomized trial. AB - PURPOSE: The advantage of chemotherapy in asymptomatic patients with advanced colorectal cancer is debatable. Whether early chemotherapy improves survival and the length of the symptom-free period versus no therapy until symptoms appear was studied in a randomized trial. PATIENTS AND METHODS: A total of 183 patients with advanced, but asymptomatic colorectal cancer were randomly allocated to receive either initial treatment with sequential methotrexate 250 mg/m2 during the first 2 hours, and fluorouracil (5-FU) 500 mg/m2 at hours 3 and 23 followed by leucovorin rescue initiated at hour 24 (MFL) for 12 courses or to primary expectancy with chemotherapy not considered until symptoms appeared. One patient was ineligible and excluded from analysis. Nine patients did not fulfill the inclusion criteria and five patients refused treatment allocation; these patients were not excluded from the study population so as not to introduce bias. So far, 51 of 90 (60%) patients in the expectancy group have received chemotherapy. RESULTS: Overall survival was better in the MFL group than in the expectancy group (Breslow-Gehan, P less than .02; log-rank, P = .13) with a difference in median survival of approximately 5 months. Also the symptom-free period and the time to disease progression were longer in the MFL group (P less than .001), with median differences of 8 and 4 months, respectively. Toxicity to MFL treatment was low; however, three patients died because of toxicity--none of them should have received therapy because of poor performance or S-creatinine elevation. The patients maintained an excellent performance throughout the MFL treatment unless the disease was progressive. CONCLUSION: We concluded that early treatment with MFL in asymptomatic patients with advanced colorectal cancer prolongs survival, the asymptomatic period, and the time to disease progression by approximately 6 months over primary expectancy. PMID- 1588371 TI - Comparison of high-dose and low-dose radiation with and without chemotherapy for children with Hodgkin's disease: an analysis of the experience at the Children's Hospital of Philadelphia and the Hospital of the University of Pennsylvania. AB - PURPOSE: In an effort to minimize complications related to high-dose radiotherapy (RT), children with Hodgkin's disease are often treated with low-dose RT (less than 25 Gy) plus chemotherapy. We performed a retrospective study comparing the results in these children with those from children treated with higher doses of RT (30 to 40 Gy) with or without chemotherapy. PATIENTS AND METHODS: From 1970 to 1988, 121 patients younger than 18 years of age with newly diagnosed Hodgkin's disease were treated at the Children's Hospital of Philadelphia (CHOP) and the Hospital of the University of Pennsylvania (HUP). Before 1977, most children underwent laparotomy and received high-dose RT with or without chemotherapy. Since then, high-dose RT alone has been reserved for pathologic stage IA and IIA postpubertal children without large mediastinal masses. In general, most postpubertal children with stage IIB through IVB disease or large mediastinal masses and all prepubertal children have received low-dose RT plus chemotherapy without laparotomy. RESULTS: The 10-year actuarial survival for all children was 86%, and the event-free survival (EFS) was 67% (median follow-up, 6.6 years). For 58 children treated with low-dose RT plus chemotherapy, 10-year survival and EFS (median follow-up, 6.8 years) were 88% and 67%, respectively. The corresponding figures for 10-year survival and EFS in 48 children treated with high-dose RT with or without chemotherapy were 88% and 66%, respectively. In children receiving combined modality therapy, the in-field failure rate was 7% for sites given between 17.5 and 22.5 Gy and 2% for sites given more than 32.5 Gy. In children receiving RT alone, the failure rate was 5% for sites given more than 32.5 Gy. CONCLUSION: We conclude that low-dose RT plus chemotherapy has yielded results comparable to those with higher doses of RT with or without chemotherapy. PMID- 1588372 TI - Treatment of patients with relapsed and resistant non-Hodgkin's lymphoma using total body irradiation, etoposide, and cyclophosphamide and autologous bone marrow transplantation. AB - PURPOSE: Patients with non-Hodgkin's lymphoma (NHL) who do not achieve a complete response (CR) after induction chemotherapy or who relapse after achieving a CR are rarely cured of their disease by the usual salvage therapy. Success of high dose cytotoxic therapy with an autologous bone marrow transplant (AuBMT) is limited. We describe the results of a prospective single-institution study using a new conditioning regimen for patients with relapsed or resistant NHL who underwent AuBMT. PATIENTS AND METHODS: Forty-four patients were reinduced with cytotoxic therapy and then evaluated for response. All patients received the conditioning regimen of hyperfractionated total body irradiation (TBI), etoposide (VP-16), and cyclophosphamide (CTX) followed by autologous bone marrow reinfusion. RESULTS: The disease-free survival (DFS) rate was 57% with a median follow-up of 42+ months. The only variable significantly associated with DFS was the patient's remission status at AuBMT. Patients who underwent AuBMT in CR had a DFS of 80%, whereas patients who underwent AuBMT in partial response (PR) or with progressive disease (PD) had a DFS of 60% and 11%, respectively (P = .002). The major toxicity was hemorrhage at the site of bulky disease, especially in patients with residual mediastinal and/or pulmonary disease. CONCLUSION: Planned reinduction cytotoxic therapy followed by TBI, VP-16, and CTX with AuBMT is an effective treatment for patients with relapsed and resistant NHL. PMID- 1588373 TI - Survival after relapse of low-grade non-Hodgkin's lymphoma: implications for marrow transplantation. AB - PURPOSE: Despite modern therapy, patients with low-grade non-Hodgkin's lymphomas (NHLs) have a median survival of only 7 to 10 years. To determine factors that predict for short survival after relapse and thus to identify candidates for intensive investigational studies including bone marrow transplantation, we have analyzed the combined results of three Eastern Cooperative Oncology Group (ECOG) trials of initial chemotherapy for lymphoma. PATIENTS AND METHODS: All 466 patients who achieved initial complete response (CR) or partial response (PR) and had a subsequent relapse were evaluated (median follow-up, 12.6 years). Multivariate regression analysis within a training set (two thirds of cases) was verified in the remaining one-third (validation set) of cases. RESULTS: Age younger than 60 years, CR, and response duration were significantly associated with longer survival after relapse. Multivariate analysis developed a predictive model that identified shorter survival in patients greater than or equal to 60 years, regardless of CR or response duration. Patients younger than 60 years with an initial CR of more than 1 year had a median survival of 5.9 years, those with a PR of more than 1 year had a median survival of 4.2 years, and those with a CR or PR of less than or equal to 1 year, 2.4 years (P less than .0001). Even the most favorable group had a 10-fold greater mortality compared with age-adjusted United States population rates. CONCLUSIONS: These data suggest that patients with low-grade NHLs with a less than or equal to 1-year response period have poor survival after relapse and may be candidates for aggressive salvage therapy, including transplantation. Longer initial responses lead to better survival after relapse. Clinical trials seeking to demonstrate an advantage for new treatments including transplantation will require long follow-up and comparison to control populations for meaningful analysis. PMID- 1588374 TI - Risk factors for high-dose cytarabine neurotoxicity: an analysis of a cancer and leukemia group B trial in patients with acute myeloid leukemia. AB - PURPOSE: We analyzed pretreatment characteristics of patients with postremission acute myeloid leukemia (AML) treated with high-dose cytarabine (HIDAC) during a recent Cancer and Leukemia Group B (CALGB) trial to determine risk factors associated with HIDAC neurotoxicity. PATIENTS AND METHODS: One hundred seventy six patients received at least one course of HIDAC as part of a CALGB protocol designed to determine the optimal dose of cytarabine (ara-C) for postremission treatment of AML. HIDAC consisted of 3 g/m2 ara-C infused over 3 hours at 12-hour intervals on days 1, 3, and 5. The pretreatment characteristics of 170 patients were available for risk analyses. RESULTS: Eighteen patients (10%) experienced neurotoxicity. Univariate analyses demonstrated associations between the occurrence of neurotoxicity and elevated serum creatinine, age, and alkaline phosphatase (AP). Multivariate analysis showed that these variables were independent risk factors. These findings were used to construct a risk model with the following parameters: creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40 years, and AP greater than or equal to 3 x normal. Seventeen of 46 (37%) patients with two or more of these criteria developed neurotoxicity compared with one of 124 (1%) patients with one or none. The sensitivity and specificity of this model were 94% and 81%, respectively. CONCLUSION: We conclude that patients with two or more of the following parameters may be at increased risk for HIDAC neurotoxicity: (creatinine greater than or equal to 1.2 mg/dL, age greater than or equal to 40, and AP greater than or equal to 3 x normal). However, this model should be confirmed by analysis of additional groups of patients treated with HIDAC. PMID- 1588375 TI - Constitutive production of tumor necrosis factor-alpha in hairy cell leukemia: possible role in the pathogenesis of the cytopenia(s) and effect of treatment with interferon-alpha. AB - PURPOSE: In view of the pleomorphic role cytokines play in human lymphoproliferative disorders, we investigated the possible involvement of tumor necrosis factor-alpha (TNF) in hairy cell leukemia (HCL). PATIENTS AND METHODS: The levels of TNF were measured in the serum of untreated patients, and in the culture supernatants of unstimulated and stimulated enriched hairy cells (HC). Furthermore, the presence of TNF mRNA transcripts in HC was analyzed. The possibility that HC could inhibit the in vitro growth of normal erythroid progenitors via the release of TNF was also investigated. Finally, in an attempt to correlate the circulating levels of TNF with the course of the disease, these were retested during and after treatment with interferon-alpha (IFN). RESULTS: Significantly increased levels of TNF were found in the sera of untreated HCL patients compared with normal control sera were seen from patients with other diseases (P less than .001), with values greater than 10 pg/mL in 21 of 42 samples tested. A significant decrease (P less than .01) of TNF levels was recorded following IFN-2a administration in 16 cases with detectable pretreatment serum levels of TNF. In two cases, an increase in TNF values was associated with persistence or progression of disease. The likelihood that the circulating levels of TNF were caused by the pathologic cells is supported by the evidence that purified HC may release TNF spontaneously. The values can be markedly increased following in vitro activation with the phorbol ester 12-0-tetradecanoylphorbol-13 acetate (PMA), with B-cell growth factor (BCGF), and, to a further extent, with the combination of PMA and BCGF. Furthermore, the constitutive mRNA for TNF was found in seven of eight HC samples analyzed. Although supernatants of enriched HC, were capable of reducing the growth of normal bone marrow erythroid progenitors by 50%, duplicate experiments using an anti-TNF antibody produced an almost complete disappearance of the inhibitory effect. CONCLUSION: The results of this study suggest that TNF plays an important role in the pathogenesis of the cytopenia(s) characteristically associated with HCL. PMID- 1588376 TI - Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. AB - PURPOSE: Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity. PATIENTS AND METHODS: In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5 day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20). RESULTS: In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%). CONCLUSION: These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy. PMID- 1588377 TI - Effects of sucralfate on acute and late bowel discomfort following radiotherapy of pelvic cancer. AB - PURPOSE: Radiotherapy, a cornerstone in the management of pelvic cancer, is accompanied by intestinal reactions. Therefore, we investigated the possible effects of sucralfate, an aluminium hydroxide complex of sulfated sucrose used in the treatment of gastric ulcer, in preventing radiation-induced diarrhea and bowel discomfort in patients treated with curative intention for pelvic cancer with external radiotherapy. PATIENTS AND METHODS: The study was double-blind and placebo-controlled and included 70 patients with carcinoma in the prostate or urinary bladder without distant metastases (T1-4No1xMo) and a performance status of greater than or equal to 90% on the Karnofsky scale. Radiotherapy was conventionally delivered with high-energy photons (four-field technique, the total dose 64 Gy, 2 Gy daily, total treatment time 5 to 6 weeks). Dose granules of sucralfate or placebo were dispensed to each patient 2 weeks after radiation started and continued for 6 weeks. All analyses were performed blindly. RESULTS: The frequency of defecation and stool consistency were significantly improved by sucralfate. Fourteen patients in the placebo group and three in the sucralfate group required symptomatic therapy with loperamide. One year later, the patients in the sucralfate group displayed significantly less problems with frequency of defecation, mucus, and blood in the stools compared with the placebo group. There was also a lower intake of loperamide and the weight decrease was less pronounced in the sucralfate group. There was no evidence of adverse effects associated with the use of sucralfate. CONCLUSION: It is suggested that sucralfate can be of beneficial value in diminishing bowel discomfort during treatment and, most importantly, sucralfate also reduces the late bowel disturbances that follow radiotherapeutic treatment of pelvic malignancies. The earlier proposed mechanisms of action (eg, protection of denuded mucosa, cytoprotective properties, binding bile acids) seem adequate to explain the present effects of sucralfate. PMID- 1588378 TI - Mastectomy versus breast-conserving therapy in the treatment of stage I and II carcinoma of the breast: a randomized trial at the National Cancer Institute. AB - PURPOSE: Mastectomy versus excisional biopsy (lumpectomy) plus radiation for the treatment of stage I and II breast cancer was compared in a prospective randomized study. PATIENTS AND METHODS: From 1979 to 1987, 247 women were randomized and 237 were treated on this study. All patients received a full axillary dissection and all node-positive patients received adjuvant chemotherapy with cyclophosphamide and doxorubicin. Radiation consisted of external-beam therapy to the whole breast with or without supraclavicular nodal irradiation followed by a boost to the tumor bed. RESULTS: The minimum time on the study was 18 months and the median time on the study was 68 months. No differences in overall survival or disease-free survival were observed. Actuarial estimates at 5 years showed that 85% of mastectomy-treated patients were alive compared with 89% of the lumpectomy/radiation patients (P2 = .49; 95% two-sided confidence interval [CI] about this difference, 0% to 9% favoring lumpectomy plus radiation). The probability of failure in the irradiated breast was 12% by 5 years and 20% by 8 years according to actuarial estimates. Of 15 local breast failures, 14 were treated with and 12 were controlled by mastectomy; the ultimate local-regional control was similar in both arms of the trial. CONCLUSION: These data add further weight to the conclusion that breast conservation using lumpectomy and breast irradiation is equivalent to mastectomy in terms of survival and ultimate local control for stage I and II breast cancer patients. PMID- 1588379 TI - Low-dose aminoglutethimide with and without hydrocortisone replacement as a first line endocrine treatment in advanced breast cancer: a prospective randomized trial of the Italian Oncology Group for Clinical Research. AB - PURPOSE: A randomized study comparing low-dose aminoglutethimide (AG) with and without hydrocortisone (HC) was performed to investigate whether corticosteroid replacement contributes to the therapeutic effects of the drug administered as a front-line endocrine therapy in postmenopausal advanced breast cancer. PATIENTS AND METHODS: Postmenopausal patients who had not had prior endocrine therapy for advanced disease and with estrogen receptor (ER) or progesterone receptor (PgR) status positive or unknown were eligible. AG was administered at a dose of 250 mg twice a day orally (125 mg twice a day during the first month) with or without HC (20 mg twice a day orally). Seventy-nine and 74 patients were assessable for response on the AG plus HC arm and on the AG arm, respectively. The two treatment groups were well balanced and patients were largely untreated. Approximately 60% had not received any adjuvant treatment, and approximately 75% had not received any medical treatment after relapse. RESULTS: The overall responses (complete response [CR] plus partial response [PR]) were 44% and 41% for the AG plus HC and the AG arm, respectively, showing no significant difference. Time to progression (median, 8.1 and 6.3 months), duration of response (median, 15.8 and 13.7 months), and duration of survival (median, 34.2 and 36.3 months) were not significantly different between the two treatment arms. Side effects were infrequent and mild in both arms, with no significant differences. CONCLUSION: We conclude that half of the conventional daily dose of AG has optimal therapeutic activity as a front-line endocrine treatment of postmenopausal advanced breast cancer and that HC does not significantly contribute to the therapeutic effects. PMID- 1588380 TI - Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. AB - PURPOSE: We have shown previously that acquired tamoxifen resistance in an in vivo experimental model is associated with reduced tamoxifen accumulation, isomerization of trans-4-hydroxytamoxifen, and tamoxifen-stimulated tumor growth. The purpose of this study is to isolate and verify the presence of estrogenic tamoxifen metabolites in human breast tumors using high-performance liquid chromatography (HPLC) and mass-spectrometry (MS) techniques. PATIENTS AND METHODS: In the present study, we used HPLC and MS to identify the presence of estrogenic metabolites in tumor samples excised from athymic nude mice and in human breast tumors isolated from patients receiving adjuvant tamoxifen therapy. RESULTS: We identified the presence of metabolite E, a known estrogenic metabolite of tamoxifen, in tamoxifen-resistant MCF-7 human breast tumors implanted in athymic nude mice, as well as in tumors from patients with clinical resistance. Additionally, we separated another estrogenic metabolite, bisphenol, by HPLC, and this was also tentatively confirmed by MS analysis. CONCLUSION: These data suggest that cellular tamoxifen metabolism to estrogenic metabolites may in part contribute to stimulating the growth of hormone-responsive breast tumors following prolonged exposure to tamoxifen. Further evaluation of the relationship between cellular metabolism and acquired tamoxifen resistance is warranted. PMID- 1588381 TI - Cyclophosphamide pharmacokinetics: correlation with cardiac toxicity and tumor response. AB - BACKGROUND: Cyclophosphamide, which forms the nucleus for virtually all preparative regimens for autologous bone marrow transplantation (ABMT), is an alkylating agent of which cytotoxicity is not directly caused by the parent compound but by its biologically active metabolites. Its nonmyelosuppressive toxicity in the ABMT setting is cardiomyopathy. We attempted to determine any correlation between plasma levels of total cyclophosphamide and the subsequent development of cardiac dysfunction. PATIENTS AND METHODS: Analyses of plasma levels and the derivation of plasma concentration-time curves (area under the curve [AUC]) were performed in 19 women with metastatic breast carcinoma, who received a continuous 96-hour infusion of cyclophosphamide, thiotepa, and carboplatin (CTCb) with ABMT. The assay for total cyclophosphamide measures the inactive parent compound; reliable assays of the active metabolites of cyclophosphamide are not yet available. RESULTS: Six of 19 women developed moderate, but transient, congestive heart failure (CHF) as assessed by clinical and radiologic criteria. These patients had a significantly lower AUC of total cyclophosphamide (median, 2,888 mumol/L/h) than patients who did not develop CHF (median, 6,121 mumol/L/h) (P less than .002). Median duration of tumor response in these patients was also more durable; at least 22 months in patients with lower AUCs versus a median of 5.25 months in those with higher AUCs (P = .008). CONCLUSION: These pharmacokinetic data support the premise that enhancement of cyclophosphamide activation may lead to both greater tumor cytotoxicity and increased but reversible end-organ toxicity. Early analysis of pharmacokinetic data may allow modulation of cyclophosphamide administration in an attempt to enhance therapeutic efficacy. PMID- 1588382 TI - Role of the rostral superior colliculus in active visual fixation and execution of express saccades. AB - 1. In the rostral pole of the monkey superior colliculus (SC) a subset of neurons (fixation cells) discharge tonically when a monkey actively fixates a target spot and pause during the execution of saccadic eye movements. 2. To test whether these fixation cells are necessary for the control of visual fixation and saccade suppression, we artificially inhibited them with a local injection of muscimol, an agonist of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). After injection of muscimol into the rostral pole of one SC, the monkey was less able to suppress the initiation of saccades. Many unwanted visually guided saccades were initiated less than 100 ms after onset of a peripheral visual stimulus and therefore fell into the range of express saccades. 3. We propose that fixation cells in the rostral SC form part of a fixation system that facilitates active visual fixation and suppresses the initiation of unwanted saccadic eye movements. Express saccades can only occur when activity in this fixation system is reduced. PMID- 1588383 TI - How the frontal eye field can impose a saccade goal on superior colliculus neurons. AB - Saccades were electrically evoked from the frontal eye field (FEF) of two trained monkeys while saccade-cells were recorded from the intermediate layers of the superior colliculus (SC). We found that FEF microstimulation, eliciting saccades of a given vector, excited SC saccade-cells encoding the same vector and inhibited all others. Such a mechanism can prevent competing commands from arising simultaneously in different structures. PMID- 1588384 TI - Expression of 5-HT3 receptors in PC12 cells treated with NGF and 8-Br-cAMP. AB - 1. To determine the functional development of neurons, we applied nerve growth factor (NGF) or 8-bromo-cyclic-adenosine monophosphate (8-Br-cAMP) to PC12 cells and recorded the 5-hydroxytryptamine (5-HT)-induced response by the use of a patch-clamp technique. 2. Cultured PC12 cells expressed 5-HT-sensitive receptors, which are almost absent in untreated cells, in the continuous presence of NGF or 8-Br-cAMP for a period of 10 days. 3. Activation of the receptors by 5-HT produced a transient inward current. In a K(+)-free solution, the reversal potential (E5-HT) of I5-HT was +10.3 mV, and the current-voltage (I-V) relation showed inward rectification at positive potentials. 4. The permeability ratio for monovalent cations was Na+:Li+:K+:Rb+:Cs+ = 1:1.19:0.89:0.94:0.91, indicating that a 5-HT-induced current is passing through the ligand-gated large cation channel. 5. 2-Methyl-5-HT, a specific 5-HT3 agonist, induced a similar inward current, even though the current amplitude was smaller and the activation and inactivation kinetics were slower than those of 5-HT. 6. ICS-205-930, a specific 5-HT3 antagonist, inhibited the 5-HT-induced current in a concentration-dependent manner with a noncompetitive inhibition profile. Spiperone, a 5-HT1 and 5-HT2 families antagonist, and ketanserine, 5-HT2 family antagonist, did not affect the 5-HT-induced response. 7. The time to peak (tp) as well as fast and slow time constants (tau if and tau is) decreased with increasing 5-HT concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588385 TI - Physiological and morphological correlations of horizontal cells in the mudpuppy retina. AB - 1. Horizontal cells (HCs) of the mudpuppy (Necturus maculosus) retina were physiologically characterized with the use of intracellular recordings in a superfused, dark-adapted, retina-eyecup preparation. 2. Physiological analysis included an evaluation of rod versus cone input and a determination of the receptive field size with the use of a displaced slit of light. 3. The morphology of HCs was established through intracellular staining with horseradish peroxidase (HRP) and Lucifer yellow mixed in a single electrode. 4. Three types of horizontal cells were identified, each associated with a distinct morphology. Physiological subtypes included luminosity (L) and chromaticity (C) cells. Morphological diversities included single axon-bearing, multiple axon-bearing and, nonaxon-bearing cells. All C-type HCs lacked axons. 5. Approximately 90% of HCs encountered in this study were L-type cells, which received sign-conserving inputs from both rods and cones. These cell types contained one or more long axons that often stretched greater than 500 microns. This group was morphologically diverse, particularly with respect to variations in the number of axons, but we were unable to correlate this diversity with any unique set of physiological properties. 6. Several C-type HCs were identified (n = 8). These cells depolarized to a low-intensity, short-wavelength (SW) stimulus, whereas they hyperpolarized to high-intensity, long-wavelength stimuli. Morphologically, these cells were axonless (n = 4), with relatively small dendritic fields. 7. A third group of HCs were classified as "short wavelength preferring" HCs (n = 7). These cells responded better to a SW stimulus at all intensity levels. They were thus dissimilar to the common L-type HCs, which showed an apparent rod to cone transition as the stimulus intensity increased, suggestive of a shift from rod to cone preference. Morphologically, these cells were axonless (n = 2), but had broader dendritic fields than the C-type HCs. 8. Our observations indicate that the horizontal cell population of the mudpuppy retina is considerably more complex than previously supposed. The existence of both axon-bearing and axonless HCs, which could be correlated with L- and C-type physiology, implies that HCs may support more than one function in outer retina processing. PMID- 1588386 TI - Evidence that C1 and C2 propriospinal neurons mediate the inhibitory effects of viscerosomatic spinal afferent input on primate spinothalamic tract neurons. AB - 1. Lumbosacral spinothalamic tract (STT) neurons can be inhibited by noxious pinch of the contralateral hindlimb or either forelimb and by electrical stimulation of cardiopulmonary sympathetic, splanchnic, and hypogastric afferents. A previous study found that spinal transections between C2 and C4 sometimes abolished the inhibitory effect of spinal afferent input and sometimes left it intact. This suggested that propriospinal neurons in the C1 and C2 segments might mediate this effect. To test whether neurons in the C1 and C2 segments were involved in producing this inhibitory effect, the magnitude of the reduction in neural activity was measured in the same STT neuron before and after spinal transection at C1 or between C3 and C7. 2. All neurons were antidromically activated from the contralateral thalamus and thoracic spinal cord. For us to accept a neuron for analysis, the characteristics of the somatic input and the latency and shape of the antidromatic spike produced by spinal cord stimulation had to be the same before and after the spinal transection. Also, spinal transection often causes a marked increase in spontaneous cell activity, which may affect the magnitude of an inhibitory response. To avoid this confounding problem, a cell was accepted for analysis only if it showed marked inhibition of high cell activity evoked by somatic pinch before spinal transection. For analysis 13 STT neurons met these criteria: 6 neurons were in monkeys with C1 transections, and 7 neurons were in animals with transections between C3 and C7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588387 TI - Effect of viewing distance and location of the axis of head rotation on the monkey's vestibuloocular reflex. I. Eye movement responses. AB - 1. The vestibuloocular reflex (VOR) stabilizes images on the retina against movements of the head in space. Viewing distance, target eccentricity, and location of the axis of rotation may influence VOR responses because rotation of the head about most axes in space rotates and translates the eyes relative to visual targets. To study the VOR response to combined rotation and translation, monkeys were placed on a rate table and rotated briefly in the dark about a vertical axis that was located in front of or behind the eyes. The monkeys fixated a near or far visual target that was extinguished before the rotation. Eye movements were recorded from both eyes by the use of the search coil technique. 2. Peak eye velocity evoked by the VOR was linearly related to vergence angle for any axis of rotation. The percent change in the VOR with near target viewing relative to far target viewing at a vergence angle of 20 degrees was linearly related to the location of the axis of rotation. Axes located behind the eyes produced positive changes in VOR amplitude, and axes located in front of the eyes produced negative changes in VOR amplitude. An axis of rotation located in the coronal plane containing the centers of rotation of the eyes produced no modification of VOR amplitude. For any axis, the VOR compensated for approximately 90% of the translation of the eye relative to near targets. 3. The initial VOR response was not correct in magnitude but was refined by a series of three temporally delayed corrections of increasing complexity. The earliest VOR evoked eye movement (10-20 ms after rotation onset) was independent of viewing distance and rotational axis location. In the next 100 ms, eye speed appeared to be sequentially modified three times: within 20 ms by viewing distance; within 30 ms by otolith translation; and within 100 ms by eye translation relative to the visual target. 4. These data suggest a formal model of the VOR consisting of four channels. Channel 1 conveys an unmodified head rotation signal with a pure delay of 10 ms. Channel 2 conveys an angular head velocity signal, modified by viewing distance with a pure delay of 20 ms, but invariant with respect to the location of the axis of rotation. Channel 3 conveys a linear head velocity signal, dependent on the location of the axis of rotation, that is modified by viewing distance with a pure delay of 30 ms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588388 TI - Response patterns and postspike effects of peripheral afferents in dorsal root ganglia of behaving monkeys. AB - 1. The activity of single afferent units was recorded in cervical dorsal root ganglia (DRG) in two macaque monkeys as they generated alternating flexion and extension torques about the wrist during a step-tracking task. During these isometric and auxotonic muscle contractions, electromyographic (EMG) activity was recorded with electrode pairs in up to 12 independent forearm muscles. Spike triggered averages (STAs) of rectified EMG activity were used to identify afferents that were associated with correlated facilitation of active muscles. 2. Our aim was to find peripheral afferents producing postspike effects in muscles and to compare their properties with those of corticomotoneuronal (CM) and rubromotoneuronal (RM) cells previously obtained under identical behavioral conditions. We documented the timing, magnitude and distribution of their postspike facilitation (PSF) of forearm muscles and investigated the response properties of task-related units. 3. Of 125 afferent units tested with STAs, 68 showed PSF of EMG activity in at least one muscle. Fifty-nine DRG units provided sufficiently long recordings to generate averages with greater than or equal to 2,000 triggers, the minimum number considered to demonstrate reliable effects. Of these 59 units, 29 (49%) were associated with facilitation of forearm muscle activity. 4. Many STAs showed a gradual increase in EMG activity starting before or near the afferent trigger spike; often superimposed on this broad facilitation was a sharply rising PSF starting at a longer latency. The earliest poststimulus facilitation evoked by single microstimuli delivered in DRG occurred in stimulus triggered averages at a latency of 3.5 ms. In STAs the broad facilitation beginning at latencies shorter than the responses to electrical stimulation was attributed to synchronous discharges in other afferent units. The sharper postspike EMG increases occurring with latencies of greater than or equal to 3.5 ms were identified as PSF produced by the afferent. The PSF parameters documented in this study were measured after subtracting the effects of synchrony facilitation. 5. PSF of EMG activity began at a mean latency of 5.8 +/- 0.3 (SE) ms and peaked at a mean latency of 7.5 +/- 0.3 (SE) ms. In previous studies, the PSFs from CM and RM cells had mean onset latencies of 6.3 and 5.6 ms, respectively, and mean peak latencies of 10.2 and 9.1 ms. 6. A measure of the PSF amplitude is the mean percent increase (MPI), defined as the increase of the PSF above its base measured as a percentage of the prespike baseline mean.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588389 TI - Functional connectivity between brain stem midline neurons with respiratory modulated firing rates. AB - 1. Recent evidence supports the idea that neurons distributed along the midline of the brain stem contribute to the regulation of breathing. This study sought evidence for functional connections between midline neurons with respiratory modulated firing rates. 2. Experiments were conducted on 38 anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Planar arrays of tungsten microelectrodes were used to monitor spike trains of two or more midline neurons simultaneously in the regions of n. raphe obscurus, n. raphe pallidus, and n. raphe magnus. Efferent phrenic nerve activity was recorded. Data were analyzed with auto- and cross-correlograms and cycle-triggered histograms. Spike trains of neurons were also tested for respiratory modulation by an analysis of variance with the use of a subjects-by-treatments experimental design. 3. Of 584 neurons studied, 99.1% were tonic, i.e., they had firing probabilities greater than zero in all phases of the respiratory cycle. Fifty three percent of the neurons had respiratory-modulated firing rates; 223 cells were more active during the expiratory (E) interval; 88 neurons were inspiratory (I)-related. The remaining cells were classified as having no respiratory-related modulation of firing rate (NRR). 4. The spike trains of 210 of 1,078 pairs (19.5%) of brain stem midline neurons exhibited short-time scale correlations indicative of paucisynaptic interactions. Primary cross-correlogram features included 129 central peaks, 45 offset peaks, two central troughs, and 57 offset troughs. Twenty-two of the neuronal pairs analyzed had both offset peaks and troughs. Correlograms from an additional 35 pairs of neurons had multiple peaks and troughs without a significant primary feature. 5. The frequency of correlations for neuron pairs composed of cells with respiratory-modulated firing rates was as follows: E-E, 40/185 (22%); E-I, 23/111 (21%); E-NRR, 45/297 (15%); I-I, 11/25 (44%); and I-NRR, 13/104 (13%). Twenty-two percent of the NRR pairs (79/357) exhibited short-time scale correlations. 6. Thirty pairs of neurons included a cell with an antidromically identified axonal projection extending to at least the third cervical segment. The mean estimated conduction velocity based on the single-site stimulation method was 26.5 +/- 9.9 (SD) m/s. 7. The results provide evidence for inhibitory and excitatory functional connections between midline brain stem neurons. Data support the hypothesis that the respiratory modulated discharge patterns of midline neurons are, at least in part, a consequence of the synaptic actions of other midline cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588390 TI - Respiratory-related neural assemblies in the brain stem midline. AB - 1. The initial objective of this study was to determine whether respiratory related neural assemblies exist in the brain stem midline. A second goal was to seek evidence for concurrent relationships among the neurons that could generate the detected synchrony. 2. Experiments were conducted on anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Spike trains of four to nine simultaneously monitored neurons were recorded in the regions of n. raphe obscurus-n. raphe pallidus and n. raphe magnus. 3. Data were analyzed with cycle triggered histograms, cross-correlograms, snowflakes, and the gravitational representation. A significance test for the gravity method was developed and tested with spike trains generated by simulated networks with defined connections. 4. Ninety-three groups of neurons from 24 cats were studied. Thirty nine groups from 19 cats included neurons that discharged synchronously on a millisecond time scale; less than or equal to 19 pairs of synchronously discharging neurons were found in one group. Twenty-seven of these 39 groups included neurons that had respiratory-modulated firing rates and discharged synchronously with other group members. Synchronous assemblies included cells monitored at rostral or caudal locations, or both. 5. Six classes of relationships were inferred from groups of neurons with multiple correlations: divergence (n = 11); convergence (n = 7); connections with opposite actions between neurons (n = 5); projections of synchronous neurons to separate targets (n = 5); projections to one neuron in a synchronous group (n = 4); and projections between two synchronous groups with common elements (n = 6). 6. The results document the existence of assemblies of synchronously discharging respiratory-related neurons in midline regions of the brain stem and suggest that divergent excitatory and inhibitory connections within the midline participate in the generation of that synchrony. Links between assemblies may operate to stabilize their collective activity in a particular state. PMID- 1588391 TI - Dynamic reconfiguration of brain stem neural assemblies: respiratory phase dependent synchrony versus modulation of firing rates. AB - 1. The objective of this work was to determine whether configurations of midline brain stem neural assemblies change during the respiratory cycle. 2. Spike trains of several single neurons were recorded simultaneously in anesthetized, paralyzed, bilaterally vagotomized, artificially ventilated cats. Data were analyzed with cross-correlational and gravity methods. 3. Sequential samples from each of eight groups of neurons known to contain synchronously discharging neurons exhibited temporal variations in that synchrony. 4. Gravity analysis of short (less than 200-s) samples of spike train data revealed 20 pairs of clustered particles that were not predicted from cross-correlation analysis of the parent data sets (greater than 20 min). 5. Twenty-nine groups of three to eight simultaneously monitored neurons, each with at least two synchronously discharging neurons, were analyzed for evidence of respiratory phase-dependent modulation of that coordinated activity. Spikes from successive interleaved inspiratory and expiratory intervals were analyzed separately. 6. Neurons pairs in 11 groups were more synchronous during the inspiratory interval; six groups had pairs that were more synchronous during the expiratory period. In two groups, different pairs were synchronous in different respiratory phases. In 11 of the 26 pairs that exhibited phase-dependent differences in synchrony, neither neuron had a respiratory-modulated firing rate as judged by either the cycle-triggered histogram or an analysis of variance of their firing rates. 7. Configurations of respiratory-related brain stem neural networks changed with time and the phases of breathing. Neurons with no apparent respiratory modulation of their individual firing rates collectively exhibited respiratory phase-dependent modulation of their impulse synchrony.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588392 TI - Two components of muscle activation: scaling with the speed of arm movement. AB - 1. The temporal waveform of muscle activity was related to the speed of arm movement. Speed was expressed in terms of the duration of a fixed amplitude movement or the "movement time." 2. Human subjects moved their arms to targets in three-dimensional space. The right arm started at a standard initial position and moved directly to the target in a single stroke. The targets were placed in various directions in a vertical plane. The arm movements consisted of shoulder and elbow rotations. 3. Subjects were required to vary the speed of their movements. In most of the experiments, trials with different movement times were randomly ordered. One of the experiments also included randomly interspersed static trials, in which the subject held the arm still at the initial posture, the final posture, or halfway between the two extremes. 4. Electromyographic (EMG) activity was recorded from several superficial elbow and/or shoulder muscles. The time base of rectified EMG records was normalized for movement time such that records from movements with various speeds were compressed to align the ending times of the movements. 5. A principal component (PC) analysis revealed that the compressed EMG waveforms could be described by a summation of PC1 and PC2 waveforms; each individual EMG waveform was approximated by a weighted sum of these two components. 6. The PC1 weighting coefficients scaled down in a monotonic relationship with movement time such that the fastest movement corresponded to a large positive weighting coefficient and the slowest movement corresponded to a small positive weighting coefficient. The PC2 weighting coefficients exhibited a similar monotonic scaling, but the values ranged from positive to negative. Further analysis demonstrated that these two components can be mathematically transformed into a tonic waveform with a constant mathematically transformed into a tonic waveform with a constant weighting coefficient and a phasic waveform with positive weighting coefficients that scale down with movement time. 7. The amplitude scaling of EMG records cannot be described by a single component, but instead requires a summation of two separate components. The tonic component may correspond to the force element needed to counteract gravity, because the magnitude of this element does not scale with movement speed. The phasic component may correspond to the force element that scales quadratically to produce a linear increase in velocity. PMID- 1588393 TI - Characteristics of near response cells projecting to the oculomotor nucleus. AB - 1. Previous work has shown neurons just dorsal and lateral to the oculomotor nucleus that increase their firing rate with increases in the angle of ocular convergence. It has been suggested that the output of these midbrain near response cells might provide the vergence command needed by the medial rectus motoneurons. However, lens accommodation ordinarily accompanies convergence, and a subsequent study showed that only about one-half of these midbrain near response cells carried a signal related exclusively to vergence. One hypothesis suggested by this finding is that this subgroup of neurons might have a unique role in providing a "pure" vergence signal to the medial rectus motoneurons. 2. In the present study extracellular recordings were made from midbrain near response cells in monkeys while eye position and lens accommodation were measured. The monkeys viewed targets through an optical system that allowed the accommodative and ocular vergence demands to be manipulated independently. This approach was used to produce a partial dissociation of accommodative and vergence responses, so that an accommodative and vergence coefficient could be determined for each cell, by the use of the following equation FR = R0 + kda x AR + kdv x CR where FR is the firing rate of the near response cell, R0 is the predicted firing rate for a distant target, kda is the (dissociated) accommodation coefficient, AR is the accommodative response, kdv is the (dissociated) vergence coefficient, and CR is the convergence response. 3. The vergence and accommodation coefficients were determined for a large number of midbrain near response cells, including a subset that could be antidromically activated from the medial rectus subdivisions of the oculomotor nucleus. Some near response neurons were found with signals related exclusively to convergence (i.e., kdv greater than 0 and kda = 0), whereas several others had signals related exclusively to lens accommodation (i.e., kda greater than 0 and kdv = 0). The majority of the near response cells had signals related to both responses (i.e., kda not equal to 0 and kdv not equal to 0). Furthermore, the vergence and accommodation coefficients of near response cells appeared to be continuously distributed. Some cells had negative accommodation or vergence coefficients. 4. The 17 near response cells that could be antidromically activated from the oculomotor nucleus presumably provide vergence signals to the medial rectus motoneurons. Although all had positive vergence coefficients, only four of these cells carried signals that were related exclusively to vergence.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588394 TI - Neuronal responses to static texture patterns in area V1 of the alert macaque monkey. AB - 1. We recorded responses from neurons in area V1 of the alert macaque monkey to textured patterns modeled after stimuli used in psychophysical experiments of pop out. Neuronal responses to a single oriented line segment placed within a cell's classical receptive field (CRF) were compared with responses in which the center element was surrounded by rings of elements placed entirely outside the CRF. The orientations of the surround elements either matched the center element, were orthogonal to it, or were random. 2. The addition of the textured surround tended to suppress the response to the center element by an average of 34%. Overall, almost 80% of the 122 cells analyzed in detail were significantly suppressed by at least one of the texture surrounds. 3. Cells tended to respond more strongly to a stimulus in which there was a contrast in orientation between the center and surround than to a stimulus lacking such contrast. The average difference was 9% of the response to the optimally oriented center element alone. For the 32% of the cells showing a statistically significant orientation contrast effect, the average difference was 28%. 4. Both the general suppression and orientation contrast effects originated from surround regions at the ends of the center bar as well as regions along the sides of the center bar. 5. The amount of suppression induced by the texture surround decreased as the density of the texture elements decreased. 6. Both the general suppression and the orientation contrast effects appeared early in the population response to the stimuli. The general suppression effect took approximately 7 ms to develop, whereas the orientation contrast effect took 18-20 ms to develop. 7. These results are consistent with a possible functional role of V1 cells in the mediation of perceptual pop-out and in the segregation of texture borders. Possible anatomic substrates of the effects are discussed. PMID- 1588395 TI - Respiratory and locomotor patterns generated in the fetal rat brain stem-spinal cord in vitro. AB - An in vitro brain stem-spinal cord preparation from last trimester (E13-E21) fetal rats, which generates rhythmic respiratory and locomotor patterns, is described. These coordinated motor patterns emerge at stages E17-E18. Synchronous rhythmic motor activity, not clearly characterized as respiratory or locomotor, can occur as early as E13. With this preparation, it is now possible to study the ontogenesis of circuits and cellular mechanisms underlying these critical movements. PMID- 1588396 TI - Statistical investigation of lower distal free-end denture design used by general practitioners in Japan. AB - Tooth loss eventually occurs in most adults, and masticatory function is restored with a prosthesis such as a fixed crown & bridge, removable partial denture (RPD), or complete denture according to the extent of loss. For the RPD there are different structural-element combinations and different designs that can be applied to the same loss pattern, so that the effect and prognosis vary. Results from a statistical investigation of removable distal free-end dentures in Japan suggested that in many cases, insufficient consideration was given to mechanical stability and protection of remaining peripheral tissue in the design of removable partial dentures. PMID- 1588397 TI - Wear of denture teeth by use of metal plates. Part 2: Abrasive wear of posterior teeth. AB - An in vitro study was conducted to evaluate the abrasive wear resistance of high strength denture teeth (HS teeth). Eight types of specimen were used in the experiments; 3 types of HS teeth, 3 types of conventional plastic denture teeth (PL teeth), porcelain teeth and metal teeth. Sliding-induced wear tests were conducted by sliding the samples on a metal plate. The abrasive wear resistance of the samples was evaluated in terms of wear depth, weight loss and SEM observation. Comparison of wear depth showed that abrasive wear resistance of HS teeth was 4.7 times that of PL teeth, 0.7 times that of porcelain teeth and 8.3 times that of metal teeth. In terms of weight loss, the corresponding values were 3.3-fold, 0.2-fold and 11.4-fold, respectively. PMID- 1588398 TI - Effects of various antiseptics on bacteremia following tooth extraction. AB - The effect of local irrigation of the gingival sulcus, which is considered an important source of bacteremia following dental procedures, with three different antiseptic solutions including hydrogen peroxide, chlorhexidine and povidone iodine, on the frequency of bacteremia after tooth extraction was determined, and the efficacies of the three antiseptics were compared. Although all the antiseptic solutions reduced the frequency of bacteremia to various degrees, povidone iodine was the most effective, and seemed to be the best choice since the decrease was statistically significant. Local administration of antiseptic solutions is therefore recommended as an adjuvant to systemic antibiotic prophylaxis. PMID- 1588399 TI - Effects of fibrin adhesive material (Tissucol) application on furcation defects in dogs. AB - A histological study was conducted to evaluate the effects of fibrin adhesive material (FAM) application on periodontal healing in seven experimental dogs. Bilateral class III furcation defects were surgically created at the second and third premolars, then orthodontic wires were placed around the teeth to induce periodontitis. Six weeks later, the wires were removed and the defects were treated by either surgery alone or surgery plus FAM application. A total of 21 specimens were obtained for histological and histometrical analysis on days 7, 21 and 42. The Mann-Whitney U test showed significantly more new attachment and bone regeneration in the FAM-treated group compared to the control (p less than 0.05). Surgery plus FAM application in the treatment of class III furcation defects seemed to be effective in promoting connective tissue attachment and bone regeneration. PMID- 1588400 TI - Retrospective evaluation of surgical intervention following chemo- and radiotherapy of maxillary sinus cancers. AB - During the past 15 years, 30 patients with squamous cell carcinomas of the maxillary sinus were treated by modified partial maxillectomy following chemo- and radiotherapy, taking care to preserve facial contour and function as far as possible. Follow-up evaluation showed that local recurrences, and regional lymph node and distant metastases were more frequent in T4 patients than in T3 patients. Evaluation of the histopathological effects of preoperative chemo- and radiotherapy at the time of surgery showed that T4 patients tended to have a poorer response to the treatment than T3 patients. Analysis according to the direction of primary tumor extension showed that the incidence of local recurrence was higher in the superolateral type, whereas that of regional lymph node metastasis was higher in the medial type. The cumulative 5-year survival was high (72.2%) in Stage III patients and low (22.5%) in Stage IV patients. The overall rate was 55.4%. The treatment produced relatively good outcomes in T3 patients but poor outcomes in T4 patients. These findings indicate that T4 carcinoma of the maxillary sinus must be managed initially by a combination of irradiation and multi-chemotherapeutic drugs, and then treated by more extensive surgical resection. PMID- 1588401 TI - Orthodontic intervention in adult patients as an adjunct to prosthetic and restorative dentistry. AB - Combined orthodontic-prosthodontic procedures will enhance the results of restorative treatment in adult patients. Restoration of malposed teeth using prostheses alone will fail both esthetically and functionally. Rotation, spacing or crowding and tipped teeth will compromise the final restoration if left untreated. Correction of axial inclination will prevent pulp exposure during preparation, as well as improving the periodontal status of the involved teeth. Cooperation between the orthodontist and the prosthodontist will ensure a more favorable final result. Cases treated in this manner are presented, illustrating the orthodontic treatment and the successful end results. PMID- 1588402 TI - A collection of doctoral dissertations at Nihon University School of Dentistry. 1991. Abstracts. PMID- 1588403 TI - Fresh autogenous rib cartilage graft to the malar process of rats with and without removal of the perichondrium: a histological study. AB - A comparison was made of autogenous grafts of rib cartilage with and without removal of the perichondrium, applied to the malar process of rats. Seventy-two male albino rats were divided into two groups according to the kind of graft received by each animal. The experimental periods were 5, 10, 20, 30, 60 and 120 postoperative days. The results showed that, in the control group, the grafts maintained their vitality for the whole experimental period and the perichondrium was biologically integrated into the host bed. Appositional growth was also observed. The treated animals showed intense resorption of the grafts and more intense bone neoformation. The newly formed bone was in intimate contact with the graft in both groups. PMID- 1588405 TI - Surgical excision of giant cerebellar hemispheric arteriovenous malformations following preoperative embolization. Report of two cases. AB - The authors present two cases of giant cerebellar hemispheric arteriovenous malformation (AVM) managed with staged preoperative embolization and surgical resection. A new embolization technique is described, combining injection of estrogen alcohol and polyvinyl acetate into AVM's by superselective catheterization of feeding arteries. Polyvinyl acetate proved to be an ideal liquid embolic material; because it polymerizes quickly and remains in a gelatinous state after injection, there was no difficulty in cutting and retracting the obliterated AVM during surgery. Intraoperative digital subtraction angiography was useful for confirming complete excision of the large and complex AVM. PMID- 1588404 TI - Intra-arterial urokinase for treatment of retrograde thrombosis following resection of an arteriovenous malformation. Case report. AB - Retrograde thrombosis of feeding arteries is a potentially catastrophic complication occasionally reported following resection of arteriovenous malformations (AVM's). No successful therapy for this condition, which causes postoperative stroke, has previously been reported. A case of retrograde thrombosis of the left middle cerebral artery immediately following resection of a parietal AVM is reported in a patient with a retained intra-arterial catheter from preoperative embolization. The administration of urokinase within 4 hours of surgery resulted in dramatic clinical and angiographic improvement without hemorrhagic complications. While urokinase is considered highly experimental in this setting, this case demonstrates that thrombolytic agents should be viewed as therapeutic options worthy of further investigation. PMID- 1588406 TI - Diagnosis and treatment of Ogilvie's syndrome after lumbar spinal surgery. Report of three cases. AB - Three patients who developed Ogilvie's syndrome following lumbar spinal surgery are described. Ogilvie's syndrome, also known as pseudo-obstruction of the colon, is characterized by massive cecal distention without mechanical obstruction. If this condition is not recognized and not promptly treated, it may be complicated by cecal perforation, a life-threatening hazard. The etiology, diagnosis, management, and potential relationship between lumbar spinal surgery and Ogilvie's syndrome are discussed. PMID- 1588407 TI - Anomalous arrangement of the origins of the anterior choroidal and posterior communicating arteries. Case report. AB - A case of anomalous origin of the anterior choroidal and posterior communicating arteries in a 36-year-old woman with aneurysmal subarachnoid hemorrhage is presented. Preoperative four-vessel angiography revealed a reverse relationship of these vessels, wherein the anterior choroidal artery origin was proximal to the origin of the posterior communicating artery. This arrangement is extremely rare; the only other reported case was in a patient undergoing angiography prior to acoustic neurinoma resection. It is believed that this is the first case reported in a patient with subarachnoid hemorrhage from rupture of an aneurysm arising from a vessel of such anomalous origin. PMID- 1588408 TI - Rupture of previously documented small asymptomatic saccular intracranial aneurysms. Report of three cases. AB - In a recent study from the Mayo Clinic on the natural history of intact saccular intracranial aneurysms, none of the aneurysms smaller than 10 mm in diameter ruptured. It was concluded that these aneurysms carry a negligible risk for future hemorrhage and that surgery for their repair could not be recommended. These findings and recommendations have been the subject of much controversy. The authors report three patients with previously documented asymptomatic intact saccular intracranial aneurysms smaller than 5 mm in diameter that subsequently ruptured. In Case 1, a 70-year-old man bled from a 4-mm middle cerebral artery aneurysm that had been discovered incidentally 2 1/2 years previously during evaluation of cerebral ischemic symptoms. A 10-mm internal carotid artery aneurysm and a contralateral 4-mm middle cerebral artery aneurysm had not ruptured. Case 2 was that of a 66-year-old woman who bled from a 4-mm pericallosal aneurysm that had been present 9 1/2 years previously when she suffered subarachnoid hemorrhage (SAH) from a 7 x 9-mm posterior inferior cerebellar artery aneurysm. Although the pericallosal aneurysm had not enlarged in the intervening years, a daughter aneurysm had developed. The third patient was a 45-year-old woman who bled from a 4- to 5-mm posterior inferior cerebellar artery aneurysm that had measured approximately 2 mm on an angiogram obtained 4 years previously; at that time she had suffered SAH due to rupture of a 5 x 12-mm posterior communicating artery aneurysm. These cases show that small asymptomatic intact saccular intracranial aneurysms are not innocuous and that careful consideration must be given to their surgical repair and long-term follow-up study. PMID- 1588409 TI - Multiple vertebral hemangiomas with neurological signs. Case report. AB - A case of multiple vertebral hemangiomas with progressive neurological deficit is presented. Successful treatment was accomplished using preoperative embolization, palliative surgical decompression, and postoperative radiation therapy. The patient has remained asymptomatic for 6 years. The authors review the role of current imaging modalities and options for therapeutic intervention. Preoperative embolization, palliative surgical decompression, and postoperative radiotherapy appear to provide a satisfactory outcome in patients with multiple hemangiomas and may represent an effective alternative to more aggressive surgical intervention. PMID- 1588410 TI - Apnea testing for the determination of brain death: a modified protocol. Technical note. AB - The absence of spontaneous respirations at a PaCO2 of 60 mm Hg or above has traditionally been accepted as the respiratory criteria for the determination of brain death. The testing of patients for the presence or absence of apnea has been complicated because the rate of PaCO2 elevation may vary substantially from patient to patient, and a nonlinear relationship exists between the rate of PaCO2 increase and the duration of apnea. In an attempt to refine the apnea test and to further elucidate the physiology of hypercapnia in humans, 11 patients who met all but the respiratory criteria for brain death were evaluated using a modification of a previously utilized apnea testing protocol. All patients were brought to a PaCO2 of 40 mm Hg or above prior to the apnea test. Baseline PaCO2 ranged from 40 to 45 mm Hg in six patients (Group I) and from 46 to 51 mm Hg in five patients (Group II). The mean rate of PaCO2 increase was 5.1 +/- 1.4 mm Hg/min in Group I and 6.7 +/- 3.1 mm Hg/min in Group II. No problems with cardiovascular instability or hypoxia were encountered during testing in this series. This refinement of the apnea test allows for a streamlined and safe approach to brain death detection. PMID- 1588411 TI - The Krause operations. AB - Some of Fedor Krause's contributions to operative technique are reviewed and portrayed as fundamental steps in the progress of neurological surgery. The approaches he devised, the "Krause operations," are exposure of the trigeminal ganglion and root, of the cerebellopontine angle, and of the pituitary (transfrontal) and the pineal (supracerebellar) regions. This review recalls the significance of the aggregate body of Krause's work, which has not been fully appreciated except by his compatriots. PMID- 1588412 TI - Complications of percutaneous laser nucleolysis. PMID- 1588413 TI - Variations in the A1 segment. PMID- 1588414 TI - Chiari malformation hydromyelia vs. syringomyelia. PMID- 1588415 TI - Timing of stereotactic procedures. PMID- 1588416 TI - Radiosurgery of arteriovenous malformations. PMID- 1588417 TI - Selective dorsal rhizotomy. PMID- 1588418 TI - Major histocompatibility antigens in murine tumors. PMID- 1588419 TI - Pathogenesis of sickle-cell anemia and aneurysm. PMID- 1588420 TI - Intracranial aneurysms in sickle-cell anemia. PMID- 1588421 TI - Vestibular schwannomas. PMID- 1588422 TI - Current results of the retrosigmoid approach to acoustic neurinoma. AB - Since 1984 when cranial nerve monitoring became routinely performed at the Mayo Clinic, 255 patients have undergone 256 procedures using the retrosigmoid approach for the removal of acoustic neurinomas. Of these, 221 patients had some hearing before surgery and 52 maintained hearing following surgery. The anatomical continuity of the facial nerve was preserved in 237 of these 256 procedures. It was possible to perform a primary end-to-end anastomosis in seven of the remaining 19 patients, and one patient had a cable graft inserted. Thus, 95.7% of these patients were believed to have potential for spontaneous facial nerve function. Of the 11 patients in whom this was not possible, seven underwent early spinal accessory facial anastomosis, in two hypoglossal-facial anastomosis was performed, and two had no facial nerve procedures and have paralysis of the facial nerve. There were two deaths from a pulmonary embolus in the early postoperative period, both 4 days following otherwise uneventful surgery. The most common postoperative complication was cerebrospinal fluid leakage, which has not resulted in significant permanent morbidity although early repair for this problem is now routinely recommended. Other complications were quite rare and have generally not resulted in any major change in patient lifestyle or activity level. This review reconfirms that the retrosigmoid surgical treatment of acoustic tumors continues to be an acceptable treatment option. PMID- 1588423 TI - Hearing preservation in acoustic neurinoma surgery. AB - The authors have reviewed hearing results obtained in 99 patients operated on via the suboccipital approach for acoustic neurinoma, who were not deaf prior to surgery (pure tone average less than 70 dB). Tumor size was less than 10 mm in four cases, 10 to 19 mm in 26 cases, 20 to 29 mm in 39 cases, and 30 mm or greater in 30 cases. Removal was macroscopically complete in 92 cases and incomplete in seven, including four cases with bilateral acoustic neurofibromatosis. Hearing was preserved in 29 patients (29.3%), of whom 23 had neurinomas smaller than 30 mm and six had tumors exceeding 30 mm in size. Postoperative hearing was good in eight cases (four with neurinomas less than 20 mm and four with neurinomas greater than 20 mm), serviceable in four cases (three with neurinomas less than 20 mm and one with a tumor greater than 30 mm), and poor in 17 cases (eight with neurinomas less than 20 mm and nine with tumors greater than 20 mm). Fifty-seven patients underwent intraoperative brain-stem auditory evoked potential monitoring: the rate of hearing preservation was found to be higher in this group than in the 42 without monitoring (p less than 0.05). A statistical study using stepwise regression analysis showed that the two preoperative factors most significantly associated with postoperative hearing preservation are a good auditory level for low frequencies measured by pure tone audiometry and a small-sized tumor. Overall results indicate that, even if hearing is more easily preserved when the neurinoma is small and the preoperative auditory condition is good, the surgeon should try to save hearing in all patients who have preserved hearing before surgery. PMID- 1588424 TI - Relationship of perfusion pressure and size to risk of hemorrhage from arteriovenous malformations. AB - The relationship between the size of an arteriovenous malformation (AVM) and its propensity to hemorrhage is unclear. Although nidus volume increases geometrically with respect to AVM diameter, hemorrhages are at least as common, in small AVM's compared to large AVM's. The authors prospectively evaluated 92 AVM's for nidus size, hematoma size, and arterial feeding pressure to determine if these variables influence the tendency to hemorrhage. Small AVM's (diameter less than or equal to 3 cm) presented with hemorrhage significantly more often (p less than 0.001) than large AVM's (diameter greater than 6 cm), the incidence being 82% versus 21%. Intraoperative arterial pressures were recorded from the main feeding vessel(s) in 24 of the 92 patients in this series: 10 presented with hemorrhage and 14 presented with other neurological symptoms. In the AVM's that had hemorrhaged, the mean difference between mean arterial blood pressure and the feeding artery pressure was 6.5 mm Hg (range 2 to 15 mm Hg). In the AVM's that did not rupture, this difference was 40 mm Hg (range 17 to 63 mm Hg). Smaller AVM's had significantly higher feeding artery pressures (p less than 0.05) than did larger AVM's, and they were associated with large hemorrhages. It is suggested that differences in arterial feeding pressure may be responsible for the observed relationship between the size of AVM's and the frequency and severity of hemorrhage. PMID- 1588425 TI - The symptomatic and functional outcome of stereotactic thalamotomy for medically intractable essential tremor. AB - Eight patients with medically refractory disabling essential tremor underwent ventralis lateralis (VL) thalamotomies; the procedure was unilateral in seven cases and bilateral (staged) in the other. Contralateral tremor remained absent or markedly reduced in all patients at the time of the most recent follow-up examinations, at a mean of 17.3 months after surgery. Disability was determined by a modified form of an established rating scale for tremor, and was reduced from a mean score of 21.1 (moderate grade) to 3.9 (absent grade) (p less than 0.001). Interestingly, voice tremor was abolished or significantly improved in 71.4% of patients with preoperative voice tremor. This feature has not been reported previously. Persistent surgical morbidity was limited to two patients with mild dysarthria and one with a mild cognitive impairment. There were no surgically related deaths. It is concluded that stereotactic VL thalamotomy is a treatment option for medically intractable disabling essential tremor. PMID- 1588426 TI - Results of a prospective randomized trial for treatment of severely brain-injured patients with hyperbaric oxygen. AB - The authors enrolled 168 patients with closed-head trauma into a prospective trial to evaluate the effect of hyperbaric oxygen in the treatment of brain injury. Patients were included if they had a total Glasgow Coma Scale (GCS) score of 9 or less for at least 6 hours. After the GCS score was established and consent obtained, the patient was randomly assigned, stratified by GCS score and age, to either a treatment or a control group. Hyperbaric oxygen was administered to the treatment group in a monoplace chamber every 8 hours for 1 hour at 1.5 atm absolute; this treatment course continued for 2 weeks or until the patient was either brain dead or awake. An average of 21 treatments per patient was given. Outcome was assessed by blinded independent examiners. The entire group of 168 patients was followed for 12 months, with two patients lost to follow-up study. The mortality rate was 17% for the 84 hyperbaric oxygen-treated patients and 32% for the 82 control patients (chi-squared test, 1 df, p = 0.037). Among the 80 patients with an initial GCS score of 4, 5, or 6, the mortality rate was 17% for the hyperbaric oxygen-treated group and 42% for the controls (chi-squared test, 1 df, p = 0.04). Analysis of the 87 patients with peak intracranial pressures (ICP) greater than 20 mm Hg revealed a 21% mortality rate for the hyperbaric oxygen treated patients, as opposed to 48% for the control group (chi-squared test, 1 df, p = 0.02). Myringotomy to reduce pain during hyperbaric oxygen treatment helped to reduce ICP. Analysis of the outcome of survivors reveals that hyperbaric oxygen treatment did not increase the number of patients in the favorable outcome categories (good recovery and moderate disability). The possibility that a different hyperbaric oxygen treatment paradigm or the addition of other agents, such as a 21-aminosteroid, may improve quality of survival is being explored. PMID- 1588427 TI - Reconstruction of the third through sixth cranial nerves during cavernous sinus surgery. AB - Sixteen reconstruction procedures of the third through sixth cranial nerves were carried out in 14 patients during operations on 149 tumors involving the cavernous sinus. A direct end-to-end anastomosis was performed in five nerves, whereas in 11 cases the nerve stumps were bridged by means of an interposing nerve graft. The sixth cranial nerve was most frequently reconstructed (nine cases). In four cases, the fifth nerve or root was repaired. The third nerve was reconstructed in two patients, and the fourth nerve was repaired in only one case. Recovery of function, either partial or complete, was observed in 13 nerves: the third in two instances, the fourth in one, the fifth in three, and the sixth in seven. No return of function occurred in three nerves. In patients with a successful recovery of cranial nerve function, either binocular function or the cosmetic result was improved. These results suggest that repair of the third through sixth cranial nerves injured during surgery should be pursued in suitable patients. PMID- 1588428 TI - Neurovascular compression in trigeminal neuralgia: a clinical and anatomical study. AB - Neurovascular decompression is a widely practiced technique for the treatment of trigeminal neuralgia, and yet there is still debate as to whether the beneficial effect results from relieving the nerve of compression by an anatomically abnormal vessel or from the manipulation and trauma the nerve undergoes during the procedure. The development of this operation has been hampered by the lack of adequate anatomical studies in normal controls. The authors present a combined study of clinical and anatomical material employing standardized definitions of the neurovascular relationships in both groups. Detailed simulations of the operative procedure were carried out on fresh cadavers matched for age, sex, and side, and a technique of in situ blood vessel perfusion was developed that enabled the normal neurovascular arrangement to be observed post mortem at physiological pressures. Neurovascular compression, typified by a large vessel distorting and creating a groove in the fifth cranial nerve, was found in 37 of the 41 cases of trigeminal neuralgia; recurrence of pain did not relate to the site of compression. A follow-up study was carried out for a median of 53 months (range 12 to 103 months). No distortion was found in a total of 50 normal cadaveric dissections; however, on perfusion to physiological pressures, the percentage of nerves with vessels adjacent or in simple contact increased from 16% to 40%. This study using this new technique confirms that vascular compression of the fifth cranial nerve is an anatomical abnormality specific to trigeminal neuralgia. PMID- 1588429 TI - Cerebral blood flow and metabolism following superficial temporal artery to superior cerebellar artery bypass for vertebrobasilar occlusive disease. AB - In order to clarify the effectiveness of extracranial-intracranial bypass operations in patients with vertebrobasilar occlusive disease, the authors used positron emission tomography to investigate the cerebral blood flow (CBF) and metabolism of eight patients undergoing superficial temporal artery (STA) superior cerebellar artery (SCA) bypass procedures. In the preoperative studies, CBF in the region of the posterior fossa was low and the oxygen extraction fraction (OEF) was high, the so-called "misery perfusion syndrome." Such changes were evident in both the posterior circulation and the anterior circulation regions. Postoperatively, there was a significant increase in CBF, a significant decrease in the OEF not only in the region of posterior circulation but also over the entire brain, and a disappearance of the uncoupling between CBF and oxygen metabolism. The STA-SCA bypass procedure is effective in improving CBF and metabolism in patients with vertebrobasilar occlusive disease. PMID- 1588430 TI - The cerebral hemodynamics of normotensive hypovolemia during lower-body negative pressure. AB - Although severe hypovolemia can lead to hypotension and neurological decline, many patients with neurosurgical disorders experience a significant hypovolemia while autonomic compensatory mechanisms maintain a normal blood pressure. To assess the effects of normotensive hypovolemia upon cerebral hemodynamics, transcranial Doppler ultrasound monitoring of 13 healthy volunteers was performed during graded lower-body negative pressure of up to -50 mm Hg, an accepted laboratory model for reproducing the physiological effects of hypovolemia. Middle cerebral artery flow velocity declined by 16% +/- 4% (mean +/- standard error of the mean) and the ratio between transcranial Doppler ultrasound pulsatility and systemic pulsatility rose 22% +/- 8%, suggesting cerebral small-vessel vasoconstriction in response to the sympathetic activation unmasked by lower-body negative pressure. This vasoconstriction may interfere with the autoregulatory response to a sudden fall in blood pressure, and may explain the common observation of neurological deficit during hypovolemia even with a normal blood pressure. PMID- 1588431 TI - Patient-interactive, computer-controlled neurological stimulation system: clinical efficacy in spinal cord stimulator adjustment. AB - Over the past 20 years, continuing technical advances have rendered spinal cord stimulation an easily implemented low-morbidity technique for the management of chronic intractable pain in properly selected patients. Percutaneous methods for the insertion of arrays of multiple epidural electrodes, which are driven by noninvasively programmable "multichannel" implanted devices, have been among the most important of these technical improvements. The same implanted electronics may be used with peripheral nerve or intracerebral electrodes. If the capabilities of this new hardware are to be used to full advantage, a major investment of time and effort is required to adjust the system postoperatively for optimum effect. Ideally, these adjustments should be based upon psychophysical data, obtained in a manner that minimizes influences such as potential operator bias or stimulus presentation-order effects. These requirements have been met by the development of a computerized system designed for direct patient interaction and for greater ease of operation than the standard external devices used with these implants. The system has been tested clinically in 25 patients with spinal cord stimulation for pain. It rapidly tests the available electrode combinations and stimulus pulse parameters at a rate comparable to or greater than that of a skilled human operator using the standard device. It records detailed graphic data and patient analog ratings at varying thresholds and implements "pain drawing" methods with novel input and analytical techniques. This patient-interactive computerized system has proved to be safe and effective clinically. The time required by the average patient working with this system to adjust the stimulator is comparable to or less than the time required by the same patient working with a physician's assistant. Psychophysical data collected by the system may be correlated with clinical observations. Ongoing development will permit delivery of novel pulse sequences and protocols to assess the mechanisms by which stimulation affords relief from pain. PMID- 1588432 TI - Variations in location of the arteries coursing between the brain stem and the free edge of the tentorium. AB - The locations of arterial branches crossing the free edge of the tentorium were studied in 16 adult cadavers. Two positional variants of the superior cerebellar artery and four variants of the posterior cerebral artery were identified. The points at risk of compression by different types of transtentorial brain herniation were defined for both the arterial branches supplying the brain stem and the arterial branches supplying the cerebral hemispheres. PMID- 1588433 TI - Chronic stimulation of the Kolliker-Fuse nucleus region for relief of intractable pain in humans. AB - Chronic electrical stimulation in the periventricular or periaqueductal gray matter regions and the thalamic somatosensory relay nuclei (ventralis posteromedialis and ventralis posterolateralis) provides long-term pain relief in about 50% of patients with intractable pain refractory to other conservative and/or surgical measures. To enhance the success of electrical stimulation in relief of pain, alternative brain and brain-stem targets have been sought. A series of laboratory studies indicated that the Kolliker-Fuse nucleus and the parabrachial region may provide appropriate alternatives to the "classic" targets. This report describes six patients with intractable chronic pain of nociceptive or central origin, in whom an electrode was stereotactically implanted in the region of the Kolliker-Fuse nucleus. Kolliker-Fuse nucleus stimulation alone or in combination with stimulation in the periaqueductal/periventricular gray matter region or the somatosensory thalamic nuclei provided excellent pain relief in three of the six patients. PMID- 1588435 TI - High-energy phosphate levels in the cerebral artery during chronic vasospasm after subarachnoid hemorrhage. AB - High-energy phosphate levels were measured in the canine cerebral artery during chronic vasospasm. Subarachnoid hemorrhage and vasospasm were induced by percutaneous injections of autologous venous blood into the cisterna magna. Narrowing of the artery was confirmed by angiography 7 days later. Levels of adenosine phosphates (adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP)), guanosine phosphates (guanosine triphosphate (GTP) and guanosine diphosphate (GDP)), and creatine phosphate (CrP) in the basilar artery were quantified using high-performance liquid chromatography. The total creatine (Crtotal) content was measured by a spectrophotometric method after acid hydrolysis of CrP. Levels of ATP, GTP, and CrP were markedly reduced in the spastic arteries, and ratios of ATP:ADP, GTP:GDP, and CrP:Crtotal were significantly decreased. The results indicate a serious disturbance in the energy metabolism that takes place in the cerebral artery during chronic vasospasm. PMID- 1588434 TI - Sensitivity of human glioma and brain cells to natural killer cell lysis. Effects of serum concentration, epidermal growth factor, and time in culture. AB - Using an in vitro monolayer natural killer (NK) cytolysis assay, the authors examined the effects of serum concentration and epidermal growth factor (EGF) on sensitivity to NK cytolysis. It was found that target cells cultured in high concentrations of serum (10% fetal bovine serum (FBS)) had higher cytotoxicity levels than those in low serum concentrations (0% to 0.5% FBS). Exposure of target cells to EGF had no effect on their sensitivity to NK cytolysis. Both glioma cell lines showed decreased NK cell sensitivity with longer times in culture. The results of cytofluorometric studies on these cell lines indicate that the differences in NK cell sensitivity may reflect the growth fraction of the target population and that a population with a higher proportion of cycling cells is more susceptible to lysis by NK cells. Whether it is possible to separate the proliferative rate of these cells from their NK cell sensitivity is unknown, but worthy of consideration. PMID- 1588436 TI - Interphase cytogenetics: a new tool for the study of genetic changes in brain tumors. AB - Interphase cytogenetics is the application of nonradioactive in situ hybridization with chromosome-specific DNA probes to interphase nuclei. In this study, interphase cytogenetics was used to investigate 66 primary brain tumors (33 gliomas, 30 meningiomas, and three medulloblastomas) for numerical chromosomal aberrations of chromosomes 1, 6, 7, 10, 11, 17, 18, X, and Y. Of the 33 gliomas (17 astrocytomas grades II, III, and IV, five oligoastrocytomas, seven oligodendrogliomas, and four ependymal tumors), 22 were near diploid, while the remaining 11 showed a significant triploid or tetraploid component. The predominant specific aberrations in gliomas were an over-representation of chromosome 7 (13 cases) and an under-representation of chromosome 10 (16 cases). These changes were observed in grade III and grade IV astrocytomas, as well as in oligodendrogliomas. Other frequent numerical changes were a gain of chromosome 17 (six cases) and a loss of chromosome 18 (seven cases). This loss of chromosome 18 seemed relatively specific for gliomas with an oligodendroglial component (six cases). Only two of 33 gliomas displayed no genetic abnormality with the probes used. Seven patients with astrocytomas died of their brain tumor during the clinical follow-up period. Their astrocytomas did not show a different chromosomal constitution compared to the other gliomas. For the meningiomas, the probe panel was extended with a probe specific for chromosome 22. Loss of chromosome 22 was obvious in 21 of the 30 meningiomas, and was the sole abnormality in 11 meningiomas; in the other 10, this loss was associated with other chromosomal changes. Five of these tumors with additional aberrations were recurrent or atypical meningiomas. It is suggested that interphase cytogenetics can contribute to a better understanding of the biological behavior of these tumors and possibly result in better insights into prognosis and strategies for therapy. PMID- 1588438 TI - The murine mutation, lethal milk, results in production of zinc-deficient milk. AB - Normal or mutant pups that nurse dams homozygous for the lethal milk (lm) mutation die as a result of zinc deficiency. Previous determinations of the zinc concentration of the mutant milk have been conflicting. This work demonstrates that the amount of 65Zn recovered in the organs of pups following in intraperitoneal injection of 65Zn to lactating dams was reduced 50-60% in the stomach, 25-30% in the gut and 50-75% in the blood and carcass, for both normal and mutant pups nursing mutant dams, relative to pups nursing normal dams. For pups nursing mutant dams, the zinc concentration of the stomach and contents was determined by atomic absorption spectrometry and found to be 144 nmol/g wet wt (for mutant pups) and 147 nmol/g wet wt (for normal pups). Pups nursing normal dams had stomach zinc concentrations of 322 nmol/g wet wt (mutant pups) and 312 nmol/g wet wt (normal pups). Administration of an oral dose of 65Zn (27 kBq) to normal and mutant adult mice showed that after 24 h there was no significant difference in the distribution of 65Zn in the liver, gut, lung, spleen, kidney, brain, skin, blood, pancreas or heart or in the carcass. We conclude that the major effect of the lethal milk mutation is the production of Zn-deficient milk. PMID- 1588437 TI - Copper deficiency alters plasma pool size, percent composition and concentration of lipoprotein components in rats. AB - Forty weanling male Sprague rats were randomly assigned to two dietary treatments, copper-deficient (9.0 mumol/kg diet) and copper-adequate (102.2 mumol/kg diet). After 7 wk of treatment, reductions in body weight and hematocrit, and an increase in relative heart weight, were observed in the copper deficient rats. Plasma VLDL, LDL and HDL were isolated by ultracentrifugation and Sepharose column chromatography. In copper-deficient rats, the percent composition of protein was reduced by one-half, and triglyceride was increased by 1.6- and 2.7-fold in LDL and VLDL fractions, respectively. In VLDL, the marked increase in triglyceride was compensated by at least a 75% decrease in percent composition of cholesterol and phospholipids as a result of copper deficiency. No treatment difference in percent composition of HDL components was detected. When the data were expressed as the amount present in the vascular pool corrected for body weight, the plasma pool size of protein, triglyceride, phospholipid and cholesterol of LDL and HDL were increased twofold or more by copper deficiency. In VLDL, a sixfold increase in triglyceride, a 36% reduction in cholesterol, and no change in phospholipid and protein pool size were observed in copper-deficient rats. These data suggest that copper deficiency may enlarge the particle size but not particle number of VLDL, increase both particle size and number of LDL, and elevate particle number but not size of HDL. PMID- 1588439 TI - Cephaloridine nephrotoxicity is potentiated by selenium deficiency but not copper deficiency in rats. AB - Lipid peroxidation may contribute to the nephrotoxicity of cephaloridine, a beta lactam antibiotic. Copper and Se may protect against free radical damage, and dietary Se deficiency potentiates cephaloridine nephrotoxicity. The objectives of this study were to further investigate potentiation of cephaloridine toxicity by Se deficiency and to determine whether Cu deficiency increases cephaloridine induced injury. Weanling male Sprague-Dawley rats were fed adequate, Cu deficient, Se-deficient, and Se and Cu-deficient diets for 4 wk and subsequently injected i.p. with cephaloridine (1200 mg/kg body wt) or saline. Nephrotoxic response to cephaloridine occurred, with increased plasma urea, kidney weight, excretion of urinary enzymes, and kidney lesions. Cephaloridine also increased plasma sorbitol dehydrogenase activity. Selenium deficiency depressed kidney glutathione peroxidase activity (78%) and potentiated cephaloridine nephrotoxicity. Copper deficiency did not increase cephaloridine nephrotoxicity; the small depression (13%) in kidney Cu,Zn-superoxide dismutase activity may not have been sufficient to impair antioxidant status. However, the marked depression in kidney glutathione peroxidase activity during Se deficiency may have impaired antioxidant status and enhanced cephaloridine-induced injury. In contrast to results in the kidney, neither Se deficiency nor Cu deficiency potentiated cephaloridine hepatotoxicity, as assessed by plasma SDH activity. PMID- 1588440 TI - Retinol stimulates Golgi apparatus activity in cultured bovine mammary gland epithelial cells. AB - Biochemical and electron microscopic studies have indicated that the Golgi apparatus responds to retinol. The purpose of this investigation was to visualize and record with living cells the rapidity of the response to retinol. A rapid response of the Golgi apparatus to retinol (1.75-17.5 mumol/L) added to the culture medium was observed using video-enhanced light microscopy with bovine mammary epithelial cells. The response was manifested within 1 min as a marked movement of membranes within the Golgi apparatus zone. In subsequent electron microscope preparations of the cells, only minor changes were observed and were restricted to increased numbers of normal-appearing membranes and vesicles associated with the trans Golgi apparatus face of the retinol-treated cells. PMID- 1588441 TI - Hepatic metallothionein gene expression in toxic milk mice. AB - The toxic milk mutation (tx) in mice is an autosomal recessive condition that causes a marked hepatic accumulation of copper in adults and severe copper deficiency in the pups of tx/tx dams. We determined the concentration of metallothionein-I (MT-I) mRNA in mutant and normal animals at various stages of development and following administration of copper and zinc. In two tx/tx males the average MT-I mRNA was 329 molecules/pg RNA compared with 38 molecules/pg in normal animals. In fetal and neonatal animals the concentration of MT-I mRNA was generally the same in normal and mutant mice and was independent of copper status. Copper or zinc administration to 7-d-old pups caused a marked induction of MT-I mRNA. There was an increased response to copper administration in one mutant group, but no clear pattern of hyper-induction of the MT gene in tx/tx animals was demonstrated. The elevation of MT-I mRNA in adult toxic milk mice is likely to be a secondary consequence of copper accumulation and not a primary effect of the mutation, because high MT-I mRNA levels would have been observed in the mutant neonates and fetuses. However, the possibility that the tx mutation causes overexpression of MT in post-weaning animals cannot be excluded by these data. The results also show that copper deficiency has no effect on the fetal or neonatal expression of the MT genes. PMID- 1588442 TI - The accumulation of copper by microvillar vesicles isolated from human placenta. AB - Copper uptake from copper-dihistidine complexes by microvillar vesicles from human placenta was studied. Uptake occurred in two phases: a rapid initial binding followed by approximately linear uptake to equilibrium at approximately 5 min. The uptake showed temperature dependence, was saturable (apparent Vmax 10.5 +/- 1.6 nmol/(mg protein.4 min), apparent Km of 0.6 +/- 0.12 mumol/L) and decreased with increasing osmotic pressure, showing that the Cu uptake arose from accumulation within the vesicles and not from extravesicular binding or isotope exchange. Ceruloplasmin blocked uptake of 64Cu from 64Cu-dihistidine by the vesicles, with 50% inhibition achieved at a protein concentration of 5-10 mumol/L and a 64Cu-dihistidine concentration of 1.5 mumol/L. The effect was specific, because glucose oxidase, a noncopper protein, increased apparent uptake by binding copper and in turn being bound to the nitrocellulose membranes used to separate vesicles from incubation medium. Adding increasing concentrations of histidine also decreased uptake. The data presented indicate that the placenta can accumulate copper from copper-dihistidine, that ceruloplasmin can interfere with uptake and that this system will be very valuable in elucidating the first stage in transfer of copper across the placenta. PMID- 1588443 TI - Metabolism and disposition of erythritol after oral administration to rats. AB - The metabolism and disposition of erythritol was studied using [14C]erythritol in rats. When [14C]erythritol was administered orally at a dose of 0.1 g/kg body wt to male rats, only 6% of the total radioactivity was excreted as expired 14CO2 and 88% was excreted in the urine within 24 h. The excreted metabolite in the urine consisted of a single component identified as intact [14C]erythritol. The excretion of 14CO2 and the incorporation ratios of radioactivity into tissues increased with the oral dosage. After rats were given an intravenous injection of [14C]erythritol, approximately 1% was excreted as 14CO2 and greater than 94% was excreted in the urine as intact [14C]erythritol. The excretion of 14CO2 within 24 h was increased to approximately 10% when [14C]erythritol was administered to rats that had been adapted to erythritol by feeding a diet containing 10% erythritol for 2 wk. When [14C]erythritol was incubated in vitro with the cecal contents from rats adapted to erythritol, greater than 20% was fermented to 14CO2 and 60% to short-chain fatty acids in 6 h. These results indicate that most orally administered erythritol was excreted in the urine without any degradation and that the remainder was transferred to the lower intestine and fermented by microbes. PMID- 1588444 TI - Glucocorticoids inhibit intestinal phosphate absorption in developing rabbits. AB - Children are apt to develop osteoporosis during chronic glucocorticoid therapy, in part due to suppression of intestinal calcium absorption. Little is known about effects of glucocorticoids on phosphate absorption. To characterize effects of glucocorticoids on intestinal phosphate transport, 4-wk-old suckling rabbits were injected with methylprednisolone. Twenty-four hours following injection, phosphate transport was studied in brush border membrane vesicles. Vesicles from steroid-treated and control animals demonstrated sodium-phosphate cotransport. Uptake was significantly greater in controls than in methylprednisolone-treated animals. Controls demonstrated an "overshoot," in that peak phosphate uptake exceeded equilibrium by nearly 100%, whereas minimal overshoot was observed in methylprednisolone-treated animals. Vmax and Km for sodium-dependent phosphate transport were 556.6 +/- 13.2 pmol.mg protein-1.10 s-1 and 0.051 +/- 0.01 mmol/L, respectively, for controls and 285.4 +/- 3.5 pmol.mg protein-1.10 s-1 and 0.044 +/- 0.01 mmol/L for methylprednisolone-treated animals. Although phosphate uptake was greater in controls than in methylprednisolone-treated animals, maximal stimulation of phosphate uptake occurred between 75 and 100 mmol/L sodium in both groups. Uptake was half-maximally stimulated by 32.5 +/- 8.1 mmol/L sodium in controls and 41.4 +/- 6.2 mmol/L sodium in treated animals. These results indicate that within 24 h methylprednisolone suppressed intestinal sodium-coupled phosphate transport. This is due to decreased maximal transport capacity without changes in transporter affinity for phosphate or sodium. PMID- 1588445 TI - Metabolic responses induced by isoproterenol in ractopamine-fed pigs. AB - Ractopamine at 0 or 20 mg/kg and protein at 130 or 170 g/kg diet were used in a 2 x 2 factorial experiment arranged in six randomized complete blocks of 64-kg pigs. On d 21, pigs were intravenously administered 1 microgram isoproterenol/kg body wt, and blood was sampled at -60, -30, 0, 5, 10, 15, 20, 30, 60, 90 and 120 min relative to injection. Subcutaneous adipose tissue samples were used to measure in vitro lipolytic and lipogenic responses to isoproterenol. Regardless of dietary treatment, isoproterenol challenge induced a rapid increase in plasma glucose, nonesterified fatty acids and lactate concentrations. Pigs fed ractopamine in a 170 g protein/kg diet had a greater plasma nonesterified fatty acid response to isoproterenol challenge than pigs fed the same dietary protein but without ractopamine. There was an attenuation of plasma glucose and lactate responses to isoproterenol by chronic ractopamine feeding at both protein concentrations. Ractopamine feeding had no effect on basal lipolysis and lipogenesis in vitro. Lipolysis was elevated and lipogenesis was depressed by isoproterenol. The results suggest that ractopamine, when it improves performance and carcass composition, elicits a shift in metabolism involving increased use of fat for oxidation and potentiates the responsiveness of the adipose tissue to lipolytic cues. PMID- 1588446 TI - Iron absorption differs in piglets fed extrinsically and intrinsically 59Fe labeled sow's milk. AB - Iron bioavailability from species-specific milk is assumed to be high for the offspring, possibly due to species-specific iron-binding proteins in the milk. To assess this bioavailability using radioisotopes, the validity of extrinsic labeling technique needs to be proven. Using the suckling piglet as an animal model, we have compared iron bioavailability from sow's milk labeled extrinsically and intrinsically. During intrinsic labeling transfer into milk of 59Fe given intramuscularly was slow and was found to be at maximum 14 h post injection. Recovery of isotope in the milk was only 0.00014%. Extrinsic and intrinsic labels were distributed differently among milk fractions; intrinsic iron bound primarily to the fat fraction but the extrinsic iron bound primarily to the casein fraction. Iron retention from intrinsically labeled milk was considerably higher than from extrinsically labeled milk. These results show that the extrinsic tag method is not valid for studies on iron absorption from sow's milk and suggest that the situation may be the same for human milk. PMID- 1588447 TI - In vivo folate kinetics during chronic supplementation of human subjects with deuterium-labeled folic acid. AB - Six healthy men (22-31 y) were supplemented for 4 wk with folic acid labeled with deuterium [3',5'-2H2; 3.6 mumol/d (1.6 mg/d)] to permit evaluation of in vivo kinetics of this vitamin. Total folate in urine, serum and erythrocytes was determined by microbiological assay, and isotopic labeling of urinary and erythrocyte folate was determined by gas chromatography-mass spectrometry. During supplementation, serum folate reached maximal concentration in approximately 18 d, whereas excretion of total and deuterium-labeled folates increased rapidly and reached isotopic steady state in 1-2 wk. Isotopic labeling of erythrocyte folate increased continually over the entire supplementation period. Upon cessation of supplementation, red blood cell folate and urinary folate excretion (total and labeled) decreased linearly. The decline in total serum folate could be described with a biexponential model that yielded a slow-phase half-life of 18.7 +/- 2.3 d. This model also indicated a turnover of 4.5% of the total body folate pool per day. Pool sizes of total body folate before and after supplementation (at steady state) were calculated to be 10 mumol (4.4 mg) and 98.9 mumol (43.7 mg), respectively. These kinetic data and stable isotope methodology may be used to address a wide range of experimental questions related to folate metabolism. PMID- 1588448 TI - Varying levels of manganese and iron affect absorption and gut endogenous losses of manganese by rats. AB - The interactive effects of manganese and iron on true absorption and endogenous losses of manganese were investigated by feeding rats three levels of manganese (0.9, 48 or 188 micrograms Mn/g diet) and two levels of iron (19 or 276 micrograms Fe/g diet) for 7 wk. After 45 d, half of the rats were fed 54Mn and half were injected intraportally with 54Mn complexed to albumin. The relative distribution of 54Mn in tissues was generally similar for rats when 54Mn was administered in these two ways. Manganese-deficient animals retained more of the isotope, had both higher apparent and higher true absorption of manganese, had a greater proportion of 54Mn in their livers and had a lower proportion of 54Mn in their muscles compared with animals fed adequate or high levels of manganese. High iron intake inhibited manganese true absorption, reduced tissue manganese concentrations and inhibited heart manganese-dependent superoxide dismutase activity. However, the greatest effect of dietary iron was on mucosal cell manganese concentrations. Endogenous losses of manganese were approximately 8% of the amount of manganese actually absorbed regardless of intake. Thus, control of absorption in the gut seems to be the major way that manganese homeostasis is maintained. Furthermore, iron seems to be depressing manganese absorption by inhibiting manganese uptake into the mucosal cells. PMID- 1588449 TI - Life span is shortened in BHE/cdb rats fed a diet containing 9% menhaden oil and 1% corn oil. AB - The effects of feeding 2 or 10% fat on glucose tolerance, blood lipids, life span and tissue pathology of male BHE/cdb rats were studied. Six groups of 30 rats were fed from weaning diets containing 1% corn oil plus either 1 or 9% corn oil (CO diets). Animals that became ill and died were necropsied and their tissues were examined histologically. Glucose tolerance and blood lipids were determined at 300 and 600 d of age. At 300, 500, 600 and 700 d of age subsets of rats were killed and heart, aorta, lungs, liver, pancreas and kidneys collected for histological examination. The experiment was terminated at 700 d. Feeding the high level MO or BT diet delayed the development of glucose intolerance and lipemia. Longevity was shorter in the rats fed the high MO diet. There were few differences among the groups of rats fed the 2% fat diets with respect to glucose tolerance and lipemia. Glomerulosclerosis was observed in all rats but was more severe and appeared earlier in rats fed the high MO diet than in those fed the high CO or BT diets. In rats with severe renal lesions, mineralized foci were observed in soft tissue, notably the aorta and heart. The results of this study indicate that the source and amount of the dietary fat can influence age-related tissue changes and longevity. PMID- 1588450 TI - The dietary lysine requirement of juvenile hybrid striped bass. AB - Two experiments were conducted to determine the dietary lysine requirement of juvenile hybrid striped bass (Morone saxatilis x M. chrysops). In both experiments the diets contained 35 g crude protein/100 g diet (10 g crude protein supplied by casein and gelatin and 25 g crude protein supplied by crystalline L amino acids) and contained graded levels of L-lysine.HCl resulting in eight dietary treatments. Diets were fed to triplicate groups of fish and ranged in dietary lysine concentration from 1.2 to 2.6 g/100 g of the dry diet in Experiment 1 and from 0.8 to 2.2 g/100 g of the dry diet in Experiment 2. Weight gain and food efficiency data from Experiment 1 indicated the dietary lysine requirement to be between 1.2 and 1.4 g/100 g of the dry diet. Weight gain, food efficiency and serum lysine data from Experiment 2 confirmed the requirement to be between 1.2 and 1.4 g/100 g of the dry diet. Broken-line analysis of weight gain and food efficiency data from Experiment 2 indicated the dietary lysine requirement to be 1.4 +/- 0.2% of the dry diet, or 4.0 g/100 g of the dietary protein. Changes in the relative proportions of dietary lipid and carbohydrate between the two experiments, although maintaining similar gross energy levels, did not alter the lysine requirement estimate of juvenile hybrid striped bass. PMID- 1588451 TI - Normalization of serum calcium restores fertility in vitamin D-deficient male rats. AB - We performed experiments to determine whether treatment with vitamin D or 1,25 dihydroxycholecalciferol could reverse male infertility caused by vitamin D deficiency. Additionally, an attempt was made to distinguish between a direct and an indirect effect of 1,25-dihydroxycholecalciferol on reproductive tissue. Vitamin D-deficient male rats with impaired fertility were treated with vitamin D and 1,25-dihydroxycholecalciferol for 3 wk, then mated. Secondly, vitamin D deficient male rats were made normocalcemic by increasing dietary calcium, and their fertility was compared with that of vitamin D-deficient, hypocalcemic rats. The fertility of male rats was restored by treatment with either vitamin D or 1,25-dihydroxycholecalciferol. However, fertility was also restored in vitamin D deficient animals by feeding them a diet supplemented with high levels of calcium. These results indicate that the influence of vitamin D and its active metabolite, 1,25-dihydroxycholecalciferol, on male fertility is indirect. Vitamin D and 1,25-dihydroxycholecalciferol seemed to influence male fertility by acting on classic target tissues and regulating levels of calcium in reproductive tissues. PMID- 1588452 TI - Effect of random background inhomogeneity on observer detection performance. AB - Many psychophysical studies of the ability of the human observer to detect a signal superimposed upon a uniform background, where both the signal and the background are known exactly, have been reported in the literature. In such cases, the ideal or the Bayesian observer is often used as a mathematical model of human performance since it can be readily calculated and is a good predictor of human performance for the task at hand. If, however, the background is spatially inhomogeneous (lumpy), the ideal observer becomes nonlinear, and its performance becomes difficult to evaluate. Since inhomogeneous backgrounds are commonly encountered in many practical applications, we have investigated the effects of background inhomogeneities on human performance. The task was detection of a two-dimensional Gaussian signal superimposed upon an inhomogeneous background and imaged through a pinhole imaging system. Poisson noise corresponding to a certain exposure time and aperture size was added to the detected image. A six-point rating scale technique was used to measure human performance as a function of the strength of the nonuniformities (lumpiness) in the background, the amount of blur of the imaging system, and the amount of Poisson noise in the image. The results of this study were compared with earlier theoretical predictions by Myers et al. [J. Opt. Soc. Am. A 7, 1279 (1990)] for two observer models: the optimum linear discriminant, also known as the Hotelling observer, and a nonprewhitening matched filter. Although the efficiency of the human observer relative to the Hotelling observer was only approximately 10%, the variation in human performance with respect to varying aperture size and exposure time was well predicted by the Hotelling model. The nonprewhitening model, on the other hand, fails to predict human performance in lumpy backgrounds in this study. In particular, this model predicts that performance will saturate with increasing exposure time and drop precipitously with increasing lumpiness; neither effect is observed with human observers. PMID- 1588453 TI - Temporal impulse responses from flicker sensitivities: practical considerations. AB - The application of the transformation technique of Stork and Falk [J. Opt. Soc. Am. A 4, 1130 (1987)] to the temporal contrast sensitivity functions of patients and normal subjects brings out several pitfalls that resulted from their choices for low- and high-frequency extrapolation. Other choices, more closely reflecting the known properties of human flicker sensitivity, are proposed, and the improved recovery of the impulse response function under the improved procedure is demonstrated. PMID- 1588454 TI - Reading speed with a pixelized vision system. AB - A visual prosthesis based on electrical stimulation of the visual cortex with an array of penetrating electrodes is expected to produce pixelized visual images consisting of punctate spots of light (phosphenes). We measured reading speed in subjects viewing text with optically simulated phosphene fields in order to obtain estimates of the following design parameters for such an electrode array: pixel number, pixel spacing, and visual-field size. Comparisons were made between scanning the text with eye movements and scanning the text with head movements. The results indicate that a 25 x 25 array of pixels representing four letters of text projected on a foveal visual field of 1.7 degrees is sufficient to provide reading rates near 170 words/min with scrolled text and near 100 words/min with fixed text. PMID- 1588455 TI - Dynamics of protein recovery from process filtration systems using microporous membrane filter cartridges. AB - The purpose of this report is to address the concern for protein concentration recovery through membrane filter cartridges at the process scale. Filtration systems consisting of pre- and/or final membrane filter cartridges were evaluated for protein concentration recovery under typical manufacturing conditions of continuous flow and high throughput volumes. Results of the study conclusively demonstrate that consideration of the protein adsorptive properties and recovery performance of cartridge filters can provide efficient bio-burden and particulate control without compromising protein yields. Understanding the dynamics of protein recovery through various prefilter and final filter cartridges can play an important role in the proper selection of a filtration system to ensure optimal life and protein yield when filtering dilute protein solutions. PMID- 1588456 TI - Toxicity potential of compounds found in parenteral solutions with rubber stoppers. AB - Leached stopper components found in parenteral solutions produced by several manufacturers were identified and quantitated. Their toxicity potential was determined by comparing the types and quantities of the leached components with known toxicity levels and/or harmful effects. Toxicity potentials for benzaldehyde, 2-butoxyethanol, cyclohexanone, ethylbenzene, 1,1,2,2 tetrachloroethane, and tetrachloroethylene are listed. Breakdown products of dextrose (furfural and 5-hydroxymethylfurfural), which may also have harmful effects, were quantitated. PMID- 1588457 TI - The compendial, industry, and regulatory initiatives regarding aseptically processed sterile products. PMID- 1588458 TI - A novel formulation of an ophthalmic beta-adrenoceptor antagonist. AB - To minimize ocular discomfort while maintaining efficacy, a delivery system for a topical cardioselective beta-adrenoceptor antagonist, betaxolol was developed. Betaxolol was formulated at 0.25% concentration in a cationic exchange resin, as a suspension. A polyacrylic acid polymer was added to increase viscosity and to increase residence time in the cul-de-sac. No significant settling was observed throughout a four-week observation period. Thus, resuspension of the formulation by frequent shaking was not required for uniformity. In rabbits, the ocular bioavailability of 0.25% betaxolol suspension was equivalent to that of 0.5% betaxolol solution. PMID- 1588459 TI - Lyophilization closures for protein based drugs. AB - Rubber stopper formulations which are currently used as lyophilization stoppers vary widely in their capacities to absorb and release moisture. Release of moisture from the stopper over the shelf life of the product may result in drug degradation for extremely low cake weight products. The degree to which rubber formulations absorb water is dependent upon the components of these formulations. Independently, polymers and fillers absorb water during autoclave cycles to varying levels depending upon such factors as the solubility, structure, possibility of chemical reactions and impurity levels of these materials. Once combined into a stopper formulation, the raw materials can react to form species which further promote absorption. Data is presented comparing the absorption characteristics of low versus high absorbent rubber formulations. The release of moisture from these formulas when stoppered on vials containing dry product is also discussed. PMID- 1588460 TI - Occurrence and biochemical characterization of GTP-binding proteins in Candida albicans. AB - The activities of GTP-binding and GTPase in Candida albicans were present in the cytosol, KCl- and cholate-extractable fractions. At least two kinds of GTP binding proteins were found in the cytosolic fraction; the major one with a molecular mass of about 30 kDa and the other about 500 kDa. The former specifically bound guanine nucleotides and was most likely to bind GDP since guanosine 5'-O-(thio) triphosphate (GTP gamma S)-binding was accelerated by addition of (NH4)2SO4. The latter showed no specificity in nucleotide binding and could also bind adenine nucleotides. The proteins were not ADP-ribosylated by either pertussis toxin or cholera toxin. These results indicate that ras-like monomeric, low molecular mass GTP-binding proteins distinct from heterotrimeric G proteins such as Gi, Go and Gs are present in C. albicans. PMID- 1588461 TI - The interaction of Cryptococcus neoformans with primary rat lung cell cultures. AB - Conditions under which Cryptococcus neoformans adhered to and was internalized by primary lung epithelial cell cultures were studied. Adherence was affected by the yeast culture age, glucose concentration and growth temperature. Formalin or heat treatment did not affect yeast adherence. Trypsin treatment, however, inhibited adherence. PMID- 1588462 TI - A new, sensitive polynucleotide probe for distinguishing Candida albicans strains and its use with a computer assisted archiving and pattern comparison system. AB - The repetitive DNA sequence poly[d(GT).d(CA)],(polyGT) can be used to generate DNA fingerprints that distinguish different yeast genera. In this study we demonstrate that the probe can also be used to distinguish individual strains of clinical isolates of Candida albicans. Isolates were fingerprinted by probing Southern blots of restriction enzyme-cleaved DNA samples with radioactively labelled polyGT. The discrimination between strains was clearer than can be achieved by direct visualization of ethidium bromide stained gels and was comparable to that achieved with previous DNA probes. However, the advantage of this probe is that it is not limited to Candida species since polyGT sequences appear to be ubiquitous in eukaryotes. Fingerprints were also generated from Southern blots using a commercial (AMBIS) radioanalytical imaging computer system. A proprietary software package (MICRO PM) was effective in discriminating between the C. albicans strains. These preliminary results indicate the potential value of this probe for discrimination between Candida isolates in epidemiological studies of candidosis. PMID- 1588463 TI - Cryptococcosis in cats: clinical and mycological assessment of 29 cases and evaluation of treatment using orally administered fluconazole. AB - Twenty-nine cats with naturally occurring cryptococcosis were evaluated prior to commencing oral fluconazole therapy (25-100 mg every 12 h). Affected cats ranged from 2 to 15 years-of-age. Male cats (19; 66%) and Siamese cats (5; 21%) appeared to be over-represented in comparison to the hospital's cat population. Mycotic rhinitis was observed in 24 (83%) of the cases, although nasal cavity involvement was subtle in four animals. Disease of the skin and subcutaneous tissues was present in 15 cases (52%) and amongst these the nasal plane (seven cats) and bridge of the nose (seven cats) were most commonly involved. Primary infection of the central nervous system was not encountered, although one cat developed meningoencephalitis and optic neuritis as a sequel to longstanding nasal cavity disease. Antibodies against the feline immunodeficiency virus (FIV) were detected in eight cats (28%), and these cats tended to have advanced and/or disseminated disease. There was a tendency for cats to develop cryptococcosis during the Australian summer. Organisms were cultured from 27 cases. Cryptococcus neoformans var. neoformans was isolated from 21 cats, while C. neoformans var. gattii was identified in the remaining six. The response to oral fluconazole was excellent in this series, which included many cats with advanced, longstanding or disseminated disease. The fungal infection resolved in all but one advanced case which died after only 4 days of therapy. A dose of 50 mg per cat, given every 12 h, produced a consistently good response without side effects. Lower doses were effective in some cases, while 100 mg every 12 h was required to control the infection in one cat. Serum fluconazole levels obtained during chronic dosing (50 +/- 18 mg l-1, mean +/- SD; 50 mg per cat every 12 h) were highly variable (range 15-80 mg l-1). Concurrent FIV infection did not impart an unfavourable prognosis, although affected cats often required prolonged courses of therapy. PMID- 1588464 TI - Germination of Trichophyton mentagrophytes on human stratum corneum in vitro. AB - The emergence of germ tubes from arthroconidia of Trichophyton mentagrophytes on stripped sheets of stratum corneum from different body areas was measured. Arthroconidia increased in size and started germination by 4 h at 37 degrees C. Germ tubes originated from a point on the arthroconidium surface mid-way between the points of attachment to adjacent conidia. With further incubation arthroconidial germination increased and germ tubes extended across the stratum corneum. Histological staining of transverse sections of infected stratum corneum showed hyphae penetrating longitudinally and perpendicularly through the thickness of the stratum corneum. By 7 days' incubation hyphae started to form arthroconidia thereby completing the vegetative growth cycle of the fungus. Scanning electron microscopy revealed penetration of corneocytes by germ tubes resulting in damage to the corneocyte surface. PMID- 1588465 TI - A nationwide survey of clinical laboratory methodologies for fungal infections. AB - Many hospitalized patients are at risk for fungal infections. In order to characterize present clinical laboratory experience and facilities for diagnosis and management of fungal infections, a nationwide survey of laboratory diagnostic methodologies was conducted. Data from calendar year 1988 were collected from 71 institutions (52 university teaching hospitals and 19 community hospitals) enrolled in the Drug Surveillance Network. Surveyed hospitals received 75,828 specimens for fungal culture in 1988, representing 18,705 positive cultures from 7373 patients. About 1.3% of patients admitted to teaching or community hospitals had positive fungal cultures, the most common isolates being Candida species. Yeast identification was most commonly performed by the germ tube test and carbohydrate assimilation testing. Dimorphic fungi were identified to the species level at 67% of hospitals. Cryptococcal antigen testing was available at all hospitals, and Candida serology testing was done at 55 institutions. A small number of hospitals performed antifungal drug concentration determinations for amphotericin B (n = 9), ketoconazole (n = 7) and flucytosine (n = 12). Fungal susceptibility testing was available at 77% of hospitals, either within the institution or at an external laboratory. Laboratory testing for diagnosis and management of fungal infections represents a major laboratory investment. Proficiency in this area, along with expert clinical advice, will be needed to advance therapy of patients complicated with fungal infections during the next decade. PMID- 1588466 TI - Killing of Paracoccidioides brasiliensis conidia by pulmonary macrophages and the effect of cytokines. AB - The ability of conidia, the infectious form of the dimorphic fungus Paracoccidioides brasiliensis, to be killed in vitro by murine pulmonary macrophages was studied. Mice were immunized by intravenous injection of killed conidia, which resulted in cellular immunity demonstrated by delayed type hypersensitivity in vivo and macrophage migration inhibition factor production in vitro. Resident pulmonary macrophages from non-immune mice were able to significantly kill the conidia (28%). Such macrophages treated with supernatants (cytokines) from antigen-stimulated immune mononuclears had a markedly enhanced ability to kill conidia (73%). These results show that activated pulmonary macrophages are potent killers of conidia of P. brasiliensis and that immune mononuclears play a role in activation of macrophages. Activated macrophages may be important for pulmonary defense against the initial stages of infection with this fungus. PMID- 1588467 TI - Laboratory-acquired sporotrichosis. AB - A case of laboratory-acquired sporotrichosis is described that was associated with research activities involving isolates of Sporothrix schenckii from the 1988 sporotrichosis epidemic in the USA. Infection occurred in the absence of apparent trauma or other predisposing factors. The possibility that S. schenckii can invade healthy and intact skin is suggested. PMID- 1588468 TI - Host defense system interactions with Candida. PMID- 1588469 TI - Adult amblyopia reversed by contralateral cataract formation. AB - Two adult patients are presented whose childhood amblyopia improved markedly when the sound eye became cataractous. In each case, the amblyopic eye became the preferred eye for fixation, allowing each patient to temporarily delay cataract surgery. Most remarkably, the acuity improvement has been sustained for greater than 2 years in each patient after full visual rehabilitation of the sound eye by cataract extraction. PMID- 1588470 TI - Visual acuity after successful treatment of large macular retinoblastoma. AB - Recent trends in the treatment of retinoblastoma have favored radiation therapy as opposed to enucleation. A major determining factor in selecting radiation therapy is the possibility of useful posttreatment visual function. While the treatment of nonmacular tumors seems reasonable, little information is available about the posttreatment visual outcome of large posterior pole tumors. We treated 17 patients (20 eyes) with group III-V retinoblastoma and large posterior pole tumors with external beam radiation. Visual acuity after treatment ranged from 5/200 to 20/50. Potential posttreatment visual function was difficult to predict using such pretreatment factors as age at diagnosis, funduscopic appearance, and the number, size, and location of the tumors. Surprising visual function was obtained in some patients with multiple large macular tumors. Follow up ranged from 1 to 8 years. No patient developed metastatic disease; however, four patients required subsequent cataract extraction. This study supports the consideration of radiation therapy as the primary treatment in eyes previously felt to have a poor visual outcome. PMID- 1588471 TI - Neuroradiological features of patients with optic nerve hypoplasia. AB - Optic nerve hypoplasia (ONH) is associated with a wide range of neurological and endocrine disorders. A series of 21 patients is reported. This comprised 17 with ONH in association with manifest neurological and endocrine disturbance, 3 who were blind but who were otherwise normal, and 1 with bilateral impaired visual acuity only. All patients underwent neuroradiological and detailed ophthalmic assessment. A wide range of abnormalities was observed. The most common findings were absent septum pellucidum, hydrocephaly, and porencephaly. Evidence of hypothalamic/pituitary hormone deficiency was present in nine patients, six of whom had demonstrable intracranial radiological abnormalities. All patients except one had bilateral optic nerve hypoplasia. Most patients had poor visual acuities and nystagmus. Astigmatism was also common. Two conditions which have not previously been reported in association with optic nerve hypoplasia were found: an intracranial arachnoid cyst and an intracranial epidermoid cyst. PMID- 1588472 TI - Iatrogenic inferior rectus palsy. AB - We examined two patients who developed unilateral inferior rectus muscle palsy following inferior oblique myectomy. Surgical exploration showed a normal inferior rectus muscle and tendon in both patients. Surgical correction consisted of inferior rectus resection in one patient and inferior rectus resection combined with an ipsilateral superior rectus recession in the other. We propose inadvertent excision of the lateral portion of the inferior rectus muscle during inferior oblique myectomy as the probable mechanism of inferior rectus injury. PMID- 1588473 TI - A case of developmental glaucoma presenting with abdominal colic and subnormal intraocular pressure. AB - A healthy baby boy presented with abdominal colic. He was subsequently noted to have enlarged, edematous corneas. A clinical diagnosis of developmental glaucoma was made despite ocular hypotony. Trabeculectomies were designed to include peripheral cornea. This served as a biopsy to confirm the diagnosis and as a surgical treatment for the condition. Morphological examination of the outflow system revealed findings compatible with a diagnosis of developmental glaucoma: a hypoplastic trabecular meshwork which contained an abundance of abnormal collagenous tissue in the extracellular spaces and the presence of endothelial cells overlying a continuous collagenous membrane. In the iris stroma there were numerous abnormal blood vessels, with a paucity of mural contractile cells. PMID- 1588474 TI - Cine magnetic resonance imaging of ocular motility. AB - We describe a technique of generation of a cine motion picture of ocular movements in a patient with Duane Type II exotropia. With the magnetic resonance scanning unit, multiple scans can be sequenced to give a graphic animation to the eyes as targets are fixated across the visual field. With this technique, we were able to clearly view the contractility of the extraocular muscles and note the changes in pulling directions of the muscles in this patient. The restriction of movement due to the cocontraction of the horizontal rectus muscles was readily apparent. PMID- 1588475 TI - Adie syndrome in a child: a case report. PMID- 1588476 TI - Ophthalmic manifestations of Setleis forceps marks syndrome: a case report. PMID- 1588477 TI - Neuroretinitis in childhood. PMID- 1588478 TI - Intraocular lenses in children. PMID- 1588479 TI - Traumatic cataract surgery with intraocular lens implantation in children. AB - We evaluated our experience of intraocular lens implantation in 22 children with uniocular traumatic cataract. Good visual acuity was achieved in a large proportion of the children despite associated corneal opacities and several intraoperative and postoperative complications. Our study suggests that intraocular lens implantation may have a major role in management of monocular cataracts in children. PMID- 1588480 TI - Normal intraocular pressure in children. AB - The age-related trend values and the normal intraocular pressure (IOP) increase curve from birth through the 16th year of life were studied in 460 subjects with a noncontact tonometer (Keeler Pulsair, Keeler, Ltd, Windsor, Berks, UK). Much lower values than in adults were recorded in subjects up to the age of 3 or 4 years. This finding leads us to believe that in the treatment of infantile glaucoma IOP should be kept within the age physiologic levels, in an attempt to prevent visual field loss and optic atrophy. PMID- 1588481 TI - Changes in astigmatism after surgery for congenital ptosis. AB - To determine the effect of ptosis surgery on the astigmatic refractive error in pediatric patients, we assessed 88 eyes postoperatively at 3, 6, and 12 months. Thirty-six eyes of unilateral cases were used as controls. There was an overall increase in average astigmatic refractive error of the study group by 0.30 diopters, while the control group decreased 0.15 D. Thirty-six percent of study eyes changed by more than 0.75 D. Results were similar for both fascia lata slings and levator resections. Those patients older than 4 years showed an increase in average cylinder (0.50 D), while those younger than 4 years decreased their average cylinder (0.20 D). Careful monitoring with postoperative refractions is required in pediatric ptosis patients. PMID- 1588482 TI - Medial rectus re-recession in undercorrected esotropia. AB - Conventional surgical management of surgically undercorrected esotropia includes bilateral lateral rectus resection, marginal myotomy, and Faden operation. During a 3-year period, 10 patients with surgically undercorrected esotropia had medial rectus re-recession 13.5 mm from the limbus. Successful binocular realignment (to 10 prism diopters or less residual binocular misalignment) was achieved in 9 of the 10 cases for both near and distance measurements. PMID- 1588483 TI - Comparison of superior oblique tendon expander to superior oblique tenotomy for the management of superior oblique overaction and Brown syndrome. AB - We compared surgical results of superior oblique tenotomy to the superior oblique silicone expander for the treatment of superior oblique overaction and Brown syndrome. Of 24 patients with bilateral superior oblique overaction, 13 underwent tenotomy and 11 had the silicone expander procedure. Reduction of A-pattern to within 10 prism diopters was achieved in 12/13 (92.3%) tenotomy patients and in 10/11 (90.9%) patients undergoing silicone expander (P greater than .05). Correction of superior oblique overaction on versions to within +/- 1 dysfunction was achieved in 22/26 (84.6%) of the tenotomies, and 21/22 (95.5%) silicone expander procedures (P greater than .05). Zero superior oblique dysfunction was found after 14/26 (53.8%) tenotomy procedures versus 18/22 (81.8%) silicone expander operations (P = .041). Superior oblique paresis occurred postoperatively in 4/13 (30.8%) tenotomy patients, whereas none of the 11 patients in the silicone expander group had superior oblique paresis (P = .044). Six patients who underwent superior oblique tenotomy for superior oblique overaction had preoperative stereopsis; following surgery, only two maintained the same level of stereopsis, and three patients totally lost all stereo acuity. All patients in the silicone expander group either maintained or had improved stereo acuity postoperatively. Seven patients with true Brown syndrome were operated on: three underwent the silicone expander procedure and four had a superior oblique tenotomy with an ipsilateral inferior oblique recession. The combination of superior oblique tenotomy with simultaneous ipsilateral inferior oblique recession resulted in an undercorrection in two of the four patients, whereas all three patients in the silicone expander group showed excellent ocular motility postoperatively, with two having normal versions and one a -1 residual limitation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588484 TI - Non-thrombogenicity by novel surface modification methods. AB - Three novel methods, recently developed by us, for the synthesis of non thrombogenetic materials were reviewed. The first was the utilization of poly(vinyl sulfonate) as a heparinoid and a newly synthesized polymerizable thrombin-inhibitor. The chemicals were grafted onto the surfaces of materials. The second was the use of thrombin-substrate-analog peptide. The immobilized peptide was decomposed by blood coagulation factors and inhibited thrombus formation on the surface. The third method was the enhancement of endothelialization by immobilization of bio-signal molecules. The immobilized biosignals remarkably accelerated the growth of endothelial cells. PMID- 1588485 TI - Mandatory biological testing of Spictra Cardiotomy Reservoir. AB - Disposable rigid Spictra Cardiotomy Reservoir is one of the units used in the extracorporeal techniques during open-heart surgery. It was designed, developed, and tested by different groups of our Institute as an indigenous product to offset the prohibitive cost of the imported one. The finished device was subjected to mandatory biological tests, such as pyrogen (in vivo rabbits and in vitro Limulus Amebocyte Lysate test) and sterility tests. It can be concluded from the case study that the device deemed to have passed the test for apyrogenicity and sterility. PMID- 1588486 TI - Polymer entrapment powders for topical delivery. PMID- 1588487 TI - SPYROFLEX: a tryptosorbent wound dressing and wound closure. PMID- 1588489 TI - Changes in AIDS incidence trends in the United States. AB - Estimating the current prevalence of human immunodeficiency virus (HIV) and projecting the future incidence of AIDS require that trends in incidence be analyzed and interpreted. We analyzed AIDS incidence trends in the United States by exposure category and selected demographic factors. In 1987, the trend in United States AIDS incidence changed as growth in the number of cases diagnosed per quarter began to decline. The slowing in growth is due in large part to a plateau in quarterly incidence in men who have sex with men in the New York City, San Francisco, and Los Angeles metropolitan statistical areas (MSAs), and in injecting drug users in the New York City MSA and New Jersey. Incidence has also reached a plateau in both adult/adolescent and pediatric blood and blood product recipients. Quarterly U.S. AIDS incidence was roughly constant during 1990, but appears to have increased to a higher level during the first half of 1991. The variation in incidence trends among subgroups suggests that several factors have affected the trend in total incidence and that the burden of severe symptomatic HIV disease may be shifting. PMID- 1588488 TI - A 2-year follow-up of an anti-HIV immune reaction in HIV-1 gp160-immunized healthy seronegative humans: evidence for persistent cell-mediated immunity. AB - The first trial of an anti-HIV immunization, using a recombinant vaccinia virus expressing gp160 (rV) for priming and paraformaldehyde-fixed rV-infected PBLs and soluble gp 160 for boosting, clearly showed an in vitro HIV-protective immune reaction. This result led us to carry out an additional 2 year Phase I clinical trial in 25 HIV-seronegative volunteers, using HIV gp 160 antigens for immunization in four different protocols. The 2 year trial showed (a) the safety of the preparations, (b) a transient humoral immunity following each boost, and (c) a long-lasting memory T-cell response. Memory cytotoxic T-lymphocytes (CTLs) induced by gp 160 antigen with or without vaccinia vector lysed HLA class I restricted target cells expressing HIV-1 env antigens. These results are consistent with CTLs being an effective component of an AIDS vaccine to control cell-to-cell viral replication, dissemination in the organism, and subsequent evolution toward AIDS. PMID- 1588490 TI - Sexual behavior and risk factors for HIV infection in a group of male factory workers who donated blood in Harare, Zimbabwe. AB - Zimbabwe has experienced a rapid rise in HIV seroprevalence in recent years. As many as 1 million people (10% of the population) are predicted to become seropositive by 2000. We examined social and behavioral factors associated with HIV infection in a case-control study among male factory workers who donated blood before the launching of the AIDS Awareness Campaign. There were 188 subjects: 69 were HIV-positive and 119 were HIV-negative. High-risk behavior was common in both groups. Among seronegative men, 73.1% reported a sexually transmitted disease (STD), 55.5% reported cash payment for sex, and 73.1% had outside girlfriends. Nonetheless, HIV-positive men were more likely to report a history of STD (OR = 3.9; 95% CI = 1.5-11.9), particularly genital ulcers (OR = 2.4; 95% CI = 1.2-4.8), and extramarital partners (OR = 2.8; 95% CI = 1.1-7.1). HIV-positive men reported more lifetime partners (16.5 vs. 12; p less than 0.05) and were less likely to live with their wives (OR = 0.51; 95% CI = 0.23-1.15). Our findings support the importance of genital ulcer as a risk factor and suggest widespread high-risk sexual behavior among urban working-class men. PMID- 1588491 TI - HIV antibody testing in France: results of a national survey. AB - Data from a knowledge, attitudes, and behavior survey conducted at the end of 1988 suggest that 13% of the population in France, aged 16 to 50 years, had been tested for HIV antibodies. Geographical differences in testing were observed, with a greater number of respondents tested in the regions where AIDS is most prevalent. Important variations in the percentage of HIV antibody-tested persons were found in relation to age, education, and occupation, but not to gender. Multiple logistic regression analysis identified significant predictors of HIV antibody testing. Behavioral predictors were multiple partners (odds ratio = 2.4), anal intercourse (odds ratio = 1.8), and drug use. A positive relationship was demonstrated between HIV testing and condom use. These correlations could indicate that the opportunity for anonymous and free testing encourages high-risk individuals to be tested. PMID- 1588492 TI - Ten-year follow-up of HIV-infected homosexual men with lymphadenopathy syndrome: evidence for continuing risk of developing AIDS. AB - Seventy-five homosexual men with lymphadenopathy syndrome (LAS), subsequently shown to be seropositive for the human immunodeficiency virus (HIV), were enrolled in a prospective study in Atlanta in 1982 and 1983. Subjects have been followed up at 3- to 6-month intervals with clinical and immunologic evaluations, including analysis of T-cell subsets. As of February 28, 1991, AIDS had developed in 36 (48%) of the 75 men. The AIDS cases continued to occur through the 10th year after onset of LAS; the 10-year cumulative incidence of AIDS was 56.6% (Kaplan-Meier survival analysis). Six-year incidence rates following the first observation of a T-helper cell count greater than or equal to 500/mm3, 400 499/mm3, 300-399/mm3, 200-299/mm3, and less than 200/mm3 were 29, 35, 50, 58, and 88%, respectively. Among individual symptoms and signs, only thrush conferred a poorer prognosis (odds ratio = 5.80; 95% confidence interval, 2.93, 11.39, p less than 0.001, Mantel-Byar analysis). The risk of AIDS persists 10 years after the onset of LAS. The AIDS incidence is related directly to T-helper cell depletion; with the exception of thrush, the presence or absence of symptoms and signs appears to be of lesser prognostic significance. PMID- 1588493 TI - Cooperativity of neutralizing antibodies directed against the V3 and CD4 binding regions of the human immunodeficiency virus gp120 envelope glycoprotein. AB - Human immunodeficiency virus type 1 (HIV-1) infection elicits neutralizing antibodies directed against two discrete regions of the gp120 exterior envelope glycoprotein: the third variable (V3) loop and the CD4 binding region. Monoclonal antibodies directed against these two regions demonstrated additive or, in some cases, weakly synergistic neutralization of HIV-1 infection. Cooperativity in virus neutralization was also observed for some gp120 mutants that, in the absence of anti-V3 loop antibodies, were relatively resistant to neutralization by antibodies directed against the CD4 binding region. Although the binding of some anti-V3 region monoclonal antibodies increased the recognition of the multimeric envelope glycoproteins by anti-CD4 binding antibodies, this enhanced binding was not predictive of the degree of cooperativity observed in virus neutralization. These results suggest that elicitation of both types of neutralizing antibodies should increase the efficacy of vaccine preparations. PMID- 1588494 TI - Oral SCH 39304 as primary, salvage, and maintenance therapy for cryptococcal meningitis in AIDS. AB - To determine the efficacy and toxicity of SCH 39304 in the treatment and suppression of cryptococcal meningitis, we conducted a prospective, noncomparative study in three groups of patients: patients with acute cryptococcal meningitis, patients with acute cryptococcal meningitis in whom other therapies have failed (salvage), and patients who required maintenance therapy. As primary therapy, the patients received up to 14 days or 1 g of amphotericin B followed by SCH 39304 200 mg once daily for 12 weeks. As maintenance therapy, the patients received SCH 39304 600 mg once weekly for 12 months. Of five salvage patients, none completed the study. Two patients died, two patients clinically deteriorated, and one patient was noncompliant. Two of three patients with acute cryptococcal meningitis completed the 12-week primary therapy, and one patient was discontinued from therapy because of a skin rash (95% confidence interval, 14-100%). All four patients who were receiving weekly maintenance therapy followed up to 27 weeks were clinically stable with no change in their serum cryptococcal antigen titer from baseline when the study was prematurely terminated. Elevation of liver function test results developed in three patients and skin rash developed in one patient. The unique pharmacologic and pharmacokinetic properties of SCH 39304 (low incidence of toxicity, long serum half-life, and good penetration into the cerebrospinal fluid) lend promise to pursue other triazole antifungals at higher doses as primary therapy and less frequent dosing for maintenance therapy. PMID- 1588495 TI - Determination of salivary anticandidal activities in healthy adults and patients with AIDS: a pilot study. AB - This investigation compared the salivary anticandidal activities of 12 healthy adults with 12 hospitalized patients with AIDS. Stimulated parotid, submandibular sublingual, and whole salivas were collected during a period of 10 min, immediately acidified, boiled, and then centrifuged to isolate salivary supernatants. Supernatants were then tested for antifungal activity against Candida albicans in blastospore viability inhibition and germ tube formation assays. A unit of blastospore or germ tube antifungal activity was established as that activity yielding 90% or greater inhibition during a defined time period in each salivary assay. Each of the patients with AIDS were found to be defective in one or more of their salivary antifungal activities, and in comparison with healthy adults the differences in antifungal units per milliliter of saliva and total antifungal units were statistically significant for each saliva and each antifungal assay. Defective salivary antifungal activity may contribute to the oral candidiasis seen in patients with AIDS. PMID- 1588496 TI - Pharmacokinetic interactions of zidovudine and methadone in intravenous drug using patients with HIV infection. AB - Pharmacokinetic parameters for methadone and zidovudine (ZDV), alone and in combination, were determined in 14 HIV-infected individuals including nine former intravenous drug users (IVDU) who were receiving methadone maintenance therapy. The serum levels of methadone were measured prior to and after initiation of ZDV treatment, with each patient serving as his or her own control. Concurrent administration of ZDV did not alter either the peak methadone concentration or the area under the methadone concentration-time curve (AUC). Serum and urine ZDV and ZDV-glucuronide concentrations were measured by both high pressure liquid chromatography (HPLC) and radioimmunoassay (RIA), and pharmacokinetic parameters determined at least twice in each of nine methadone-maintained former IVDU patients initiating ZDV therapy. These parameters were compared to those for ZDV in a group of five control patients who were neither receiving methadone nor had a history of i.v. drug use. The serum ZDV levels were significantly higher in the methadone patients, with a 43% increase (p less than 0.05) over the mean AUC of 7.68 microM h observed in the control patients. Furthermore the methadone patients could be divided into two groups based on their ZDV AUC: four patients whose ZDV AUC averaged twofold higher than the control group, and five patients whose ZDV AUC were equal to control. No significant differences were found between the control and methadone groups for ZDV bioavailability or Tmax, serum half-life, glucuronidation, or urinary excretion. Methadone also did not affect ZDV glucuronidation in an in vitro assay using human hepatic microsomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588497 TI - Sex, power laws, and HIV transmission. PMID- 1588498 TI - Seroprevalence of HTLV-II in Paragaminos, state of Para, Brazil. PMID- 1588499 TI - Effects of zidovudine on EEG sleep in HIV-infected men. PMID- 1588500 TI - Lipid peroxidation in human immunodeficiency virus infection. PMID- 1588501 TI - Reversible metabolism of vitamin K-vitamin K epoxide: modeling considerations and limitations. AB - Due to the cyclical natural of the vitamin K-vitamin K epoxide system, a two compartment reversible metabolism model was used to describe this interconversion. In attempting to apply this model to the vitamin K-vitamin K epoxide cycle using literature data from dogs, interconversion and elimination clearances were obtained which are not physiologic. Consequently, the assumptions of the model were reexamined with respect to their validity. One critical assumption of the two-compartment model for interconversion is that it can only be applied in the absence of flow limitations. To determine what effect flow limitations may exert on the vitamin K and vitamin K epoxide apparent blood clearances, a model separating the liver from the blood compartment was proposed assuming the interconversion and metabolism of vitamin K and its epoxide occurred only within the liver. Simulated data suggested that if the reversible metabolic clearance values exceeded the distribution clearance terms, all the apparent clearances calculated using blood concentration-time data were in error. It is suggested that a two-compartment interconversion model might be too simplistic for the vitamin K-vitamin K epoxide cycle where the reversible metabolism is efficient and the distributional clearance may be rate limiting. PMID- 1588502 TI - Sample size determination for the two one-sided tests procedure in bioequivalence. PMID- 1588505 TI - Physiological pharmacokinetic parameters for cis-dichlorodiammineplatinum(II) (DDP) in the mouse. PMID- 1588503 TI - Axial tissue diffusion can account for the disparity between current models of hepatic elimination for lipophilic drugs. AB - An assumption of previous models of hepatic elimination is that there is negligible axial diffusion in the liver. We show, by construction of a stochastic model and analysis of published data, that compounds which are readily diffusible and partitioned into hepatocytes may undergo axial tissue diffusion. The compounds most likely to be affected by axial tissue diffusion are the lipophilic drugs for which the cell membranes provide little resistance and which are highly extracted, thereby creating steep concentration gradients along the sinusoid at steady state. This phenomenon greatly modifies the availability of the compound under conditions of altered hepatic blood flow and protein binding. For moderately diffusible compounds, these relationships are similar to those predicted by the simplistic venous-equilibrium model. Hence, the paradoxical ability of the venous-equilibrium model to describe the steady-state kinetics of lipophilic drugs such as lidocaine, meperidine, and propranolol may be finally resolved. The effects of axial tissue diffusion and vascular dispersion on hepatic availability of drugs are compared. Vascular dispersion is of major importance to the availability of poorly diffusible compounds, whereas axial tissue diffusion becomes increasingly dominant for highly diffusive and partitioned substances. PMID- 1588506 TI - Diabetic ketoacidosis during pregnancy. AB - Pregnancy increases the chances for the woman with type 1 diabetes to develop DKA, especially if the patient is noncompliant with glycemic control, if a concomitant infection occurs, or if tocolysis with a beta-adrenergic agent is necessary for preterm labor. Prompt recognition of the crisis state of DKA with immediate intervention and management is a challenge for the health care team. Approaches to correct the fluid imbalance and to restore glucose homeostasis are needed to stabilize the patient and to provide an optimum outcome for mother and fetus. The critical assessment skills of the nurse, as well as the skills to provide the emotional aspects of care, are essential for a rapid resolution of the condition. PMID- 1588504 TI - Measuring the predictive performance of computer-controlled infusion pumps. AB - Current measures of the performance of computer-controlled infusion pumps (CCIPs) are poorly defined, of little use to the clinician using the CCIP, and pharmacostatistically incorrect. We propose four measures be used to quantitate the performance of CCIPs: median absolute performance error (MDAPE), median performance error (MDPE), divergence, and wobble. These measures offer several significant advantages over previous measures. First, their definitions are based on the performance error as a fraction of the predicted (rather than measured) drug concentration, making the measures much more useful to the clinician. Second, the measures are defined in a way that addresses the pharmacostatistical issue of appropriate estimation of population parameters. Finally, the measure of inaccuracy, MDAPE, is defined in a way that is consistent with iteratively reweighted least squares nonlinear regression, a commonly used method of estimating pharmacokinetic parameters. These measures make it possible to quantitate the overall performance of a CCIP or to compare the predictive performance of CCIPs which differ in either general approach (e.g., compartmental model driven vs. plasma efflux approach), pump mechanics, software algorithms, or pharmacokinetic parameter sets. PMID- 1588508 TI - Insulin infusion therapy in the intrapartum period. AB - Glycemic control is important not only in the antepartum period but in the intrapartum period as well. Nursing management of the patient receiving insulin infusion therapy can assist in prevention of maternal and newborn morbidity. Careful glucose monitoring, insulin infusion therapy, and skilled nursing management of these complex patients result in the prevention of maternal and fetal injury and ensure a positive childbirth experience. PMID- 1588507 TI - Exercise as a treatment modality to maintain normoglycemia in gestational diabetes. AB - Exercise can be a safe alternative to insulin therapy and may possibly eliminate the need for insulin in GDM. Exercise therapy should be explored as an additional means to maintain normoglycemia, preconceptionally as well as throughout pregnancy. PMID- 1588509 TI - Gestational diabetes mellitus screening tests: a review of current recommendations. AB - Early recognition and management of gestational diabetes decreases the incidence of macrosomia. Infant morbidity and mortality are also decreased. While there continues to be little agreement regarding precise methods of screening and diagnostic criteria for GDM, most specialists recommend screening with the 50-g oral glucose load followed by a 3-hour GTT. Screening only those women with select risk factors may result in 30% to 50% of women with gestational diabetes being overlooked. Careful explanation of testing methods and implications may result in improved patient understanding of the importance of this diagnosis and of its impact on future health care needs. PMID- 1588511 TI - The premature infant with hyperglycemia: use of continuous insulin infusion. PMID- 1588510 TI - Meeting the challenge of neonatal hyperglycemia. AB - LBW and VLBW neonates have presented neonatal caregivers with a unique challenge to meet their nutritional and growth needs. Unfortunately, the neonate's immature physiologic function may lead to persistent glucose intolerance and a nonresponsiveness to endogenous insulin. The use of insulin infusions for the treatment of hyperglycemia may support normoglycemia and improve nutritional supplementation. PMID- 1588512 TI - Infants of diabetic mothers: current perspectives. AB - A thorough understanding of the metabolic alterations seen in pregnancies complicated by diabetes can help to provide the framework for comprehensive care of the mother and her infant. Nursing research may help to clarify the scope of problems encountered as well as delineating strategies to reduce mortality and morbidity. The problems encountered in infants of diabetic mothers can be better managed with a thorough understanding of the physiologic changes encountered. Assessment strategies can then be developed specific to the identified needs. Finally, interventions can be selected that promote healthy infant and family function and reduce long-term complications. Although perinatal outcomes have improved in diabetic pregnancies, there are still opportunities to reduce major complications and to improve quality of life. PMID- 1588513 TI - Glucose management and nutritional support of low-birth-weight neonates. PMID- 1588514 TI - [Neuroimmunology of fever]. PMID- 1588515 TI - Medical education in chaos. PMID- 1588516 TI - Medical research after Maastricht. PMID- 1588517 TI - Domiciliary oxygen therapy for children. Summary of a report of a working group of the Committee on Thoracic Medicine of the Royal College of Physicians. PMID- 1588518 TI - High quality long-term care for elderly people. A summary of a report of the Royal College of Physicians and the British Geriatrics Society. PMID- 1588519 TI - Heart failure in a district general hospital. AB - The frequency, clinical characteristics, and outcome of patients admitted with heart failure to a district general hospital in North-West London serving a population of approximately 155,000 was assessed over a six-month period. The number of patients with heart failure was determined by both a prospective ward survey and a retrospective study of all patient records with diagnostic codes for heart failure or pulmonary oedema. During those six months, 2,877 patients were admitted to the medical and geriatric services of whom 140 (4.9%) had heart failure. Only 29 patients in heart failure were under the age of 65 years. In 86 patients the mode of presentation was acute pulmonary oedema. Fifty-two (37%) patients had an arrhythmia at the time of admission of whom 48 had atrial fibrillation. An electrocardiogram, a chest X-ray, and an echocardiogram were performed in 137, 136, and 81 patients respectively. The aetiology of heart failure was considered to be coronary artery disease (41%), valve disease (9%), hypertension (6%), cor pulmonale (4%), a dilated cardiomyopathy (1%), congenital heart disease (1%), thyrotoxicosis (1%), and unknown (36%). During the period of hospital stay 42 patients (30%) died; a further 20 patients (14%) died in a one year follow-up. In a district general hospital heart failure is a common reason for admission and patients remain in hospital for a considerable time. Arrhythmias are commonly associated with heart failure. The prognosis is poor and the hospital mortality high. The management of heart failure is an important consideration in allocating hospital resources in a district general hospital. PMID- 1588520 TI - Schizophrenia and neurodevelopment. AB - Schizophrenia is characterised by the psychotic symptoms of hallucinations and delusions, accompanied by variable degrees of loss of insight. Whilst there is heterogeneity in the clinical profile, and presumably in the pathogenesis of what is currently called 'schizophrenia', it has become absolutely clear over the past decade that schizophrenic symptoms are consequent upon serious brain dysfunction. This new perspective has laid to rest a variety of 'crazy' theories, including the notion that mental illness was a myth, or that schizophrenia could be caused by faulty child rearing. The use of dopamine-blocking drugs has led to an improvement in symptom control, and diminished the need for prolonged hospital stays. It was hoped that the clear relationship between antipsychotic activity and dopamine blockade would help to elucidate the pathophysiology of schizophrenia, but to date no consistent abnormalities of the dopamine system have been found. Nevertheless, we have learned much about both the aetiology of schizophrenia and the origin of particular symptoms. Much of this has stemmed from increased understanding of the brain abnormalities underlying the disorder. PMID- 1588521 TI - Benefits and weaknesses of a cardiac rehabilitation programme. AB - The British Heart Foundation and the Chest, Heart and Stroke Association have allocated funds to develop cardiac rehabilitation programmes. We have recently completed and now evaluate an exercise-based rehabilitation course reinforced with advice about return to normal activity for 110 patients who had suffered acute myocardial infarction. Patients admitted to the Plymouth cardiac care unit were randomised into groups: a control group to receive standard hospital care, and a rehabilitation group who, in addition, received an exercise programme reinforced with advice. Patients were assessed at entry to the study and at intervals thereafter. Assessment was by questionnaire and objective tests consisting of a 12-minute walking test and weekly outpatient pedometry. In the rehabilitation group patients were able to walk further and faster, return to work earlier, undertake more housework, and resume normal sexual activity; they were less short of breath and did not experience more angina. However, the rehabilitation course brought little benefit to the patients' perception of well being and their anxiety about health or their outlook on life. Exercise and advice are important components of a rehabilitation programme, but more attention needs to be given to the psychological aspects of recovery from a heart attack. PMID- 1588522 TI - The pathogenesis of AIDS: classical and alternative views. AB - As HIV readily kills CD4 cells in vitro it has been widely assumed that this would account for the declining CD4 counts in vivo. A growing number of reports suggest that the pathogenesis of AIDS is considerably more complex than had been thought. A number of indirect mechanisms for CD4 cell death have been proposed. In this review of alternative theories which could explain the features of AIDS, autoreactivity and genetic restriction to the development of disease are considered the most important. In addition it is suggested that if HIV is able to mimic MHC antigens on the surface of antigen presenting cells then this could stimulate 'allo reactive' T lymphocytes, which would explain the marked similarity of HIV infection to chronic graft versus host disease. PMID- 1588523 TI - Enlarged epitrochlear lymph nodes: an old physical sign revisited. AB - Few doctors routinely examine the epitrochlear glands as part of their physical examination of a patient. No palpable epitrochlear nodes were detected in 140 healthy subjects, but palpable epitrochlear nodes were present in 27% of 184 patients with diseases in which lymphadenopathy occurs. Whilst epitrochlear nodes are commonly enlarged in specific acute, subacute, and chronic infections, they are not enlarged in the mild, transient, non-specific febrile illnesses with cervical lymphadenopathy of children and young adults. Enlarged epitrochlear glands provide a useful discriminatory sign in the diagnosis of glandular fever. Enlargement of these nodes is common in most of the lymphoproliferative disorders except Hodgkin's disease. In rheumatoid arthritis their palpability indicates activity of hand joints. The examination of epitrochlear nodes should form part of the routine physical assessment of any ill patient. PMID- 1588524 TI - Diabetic pregnancy 1977-1990: have we reached a plateau? AB - We have compared 81 pregnancies in women with type 1 (insulin dependent) diabetes in 1984-1990 with 58 in 1977-1983. In 1984-1990, women booked earlier (8 weeks [median] vs 12 weeks), mean haemoglobin A1 was lower in each trimester, and fewer days were spent in hospital before delivery (5.3 days [mean] vs 15). The latter was due to more experience in managing diabetic control as outpatients and fewer admissions for fetal monitoring. Most admissions are now for pre-eclampsia and intercurrent illnesses. The proportion of deliveries by caesarean section has not changed significantly (53% in 1984-1990 vs 66% in 1977-1983), but most are now done as emergencies. The incidence of macrosomia is constant (26% in 1984-1990 vs 21% in 1977-1983). There was one stillbirth, one intra-uterine death (complicating maternal ketoacidosis) and one perinatal death in 1984-1990, compared with no losses in 1977-1983. Two babies had major congenital abnormalities in 1984-1990, compared with one in 1977-1983. These results compare favourably with those from other centres in the United Kingdom. We conclude we have reached a nearly irreducible minimum for hospital days before delivery and congenital abnormalities, but that there is scope for a small reduction in the caesarean section rate. PMID- 1588525 TI - A comparison of workloads of physician-gastroenterologists and other consultant physicians. Prepared on behalf of the Clinical Services Committee, British Society of Gastroenterology. AB - In response to a workload questionnaire, carried out as part of an enquiry into manpower needs in gastroenterology, replies were received from 17 health regions, relating to 86 hospitals and 135 consultant gastroenterologists. The average yearly number of deaths and discharges of patients under the care of gastroenterologists was 992, while that of patients cared for by consultant physicians in other specialties was 679. When daycase admissions were also included, there were 1,553 annual discharges per gastroenterologist as compared with 871 for other physicians. These 682 extra cases per gastroenterologist largely represent the additional workload of gastrointestinal endoscopy. PMID- 1588526 TI - An improved 'interim discharge letter' a successful outcome from audit. AB - General practitioners were dissatisfied with this hospital's interim discharge letters. These were unstructured letters written by house officers shortly after the patient's discharge. A copy of the list of drugs prescribed on discharge was sent separately. After discussing the various needs with general practitioners a new form of discharge letter has been successfully introduced. The layout has been further modified in the light of feedback, and details of the new letter are presented. The new form has been well received by hospital staff and general practitioners. The paperwork for junior doctors has been reduced by the inclusion of the prescription in the discharge letter. PMID- 1588527 TI - Setting district stroke standards and objectives. A Report of the West Lambeth Health Authority Stroke Steering Group. AB - Although stroke is a common disease consuming considerable NHS resources little is known about how effectively these resources are distributed. A local district stroke register has revealed the burden and pattern of care for stroke patients locally which has prompted the setting up of a stroke steering group whose aim is to promote the effective local use and provision of services for stroke patients. The multidisciplinary group has adopted the Royal College of Physicians' recommendations on stroke care for local use and incorporated them into a document which has been distributed to all health care professionals managing stroke patients. The group has also devised a standardised clerking proforma to collect data with which to audit stroke care. Based on these recommendations, standards have been set in the main domains of care for stroke patients with the aim of improving stroke services locally. Having identified local problems in the provision of care, set standards and devised a mechanism for the audit of stroke care, the district is now hopefully in a position to effect change and close the audit loop. PMID- 1588528 TI - Medical audit: the differing perspectives of managers and clinicians. AB - The objectives of this study were to gauge the attitudes and perceptions of managers and clinicians to medical audit, and to identify differences which might be barriers to the effective implementation of audit. A questionnaire survey of consultants and health service managers in one health district was conducted prior to the introduction of medical audit. Replies were received from 113/144 (78%) clinicians and 53/70 (76%) managers. Managers and clinicians concurred about the potential benefits of audit but had divergent opinions regarding its disadvantages. Seventy-one per cent of clinicians thought that audit would interfere with clinical work and 41% that audit would consume resources that could be better used on patient care. Only one in eight managers shared these views. Clinicians were divided on the threats to clinical autonomy and were three times more likely than managers to agree that audit would enable managers to influence medical practice. Most clinicians considered that audit would require one session a week, while 49% of responding managers thought audit could be performed within existing timetables. Although managers and clinicians are broadly in favour of the introduction of audit, they differ in their assessment of the time required and the opportunity costs. Appreciation of these differing perspectives should facilitate the effective introduction of audit. PMID- 1588530 TI - Education and training for senior house officers. Recommendations of the Education Committee of the Royal College of Physicians. PMID- 1588529 TI - Auditing a research ethics committee. AB - Research ethics committees approve research on human subjects performed locally. They have been criticised for failing to perform this function adequately. I have, therefore, examined the structure and process of the committee for Leicestershire and compared it with the guidelines for these committees produced by the Royal College of Physicians and the Department of Health. The structure and function of the committee are described and conform well with the recommendations of the Royal College of Physicians and the Department of Health. An annual report to the health authority has not previously been produced but the need for this is now accepted. The suggestion for a lay chairman or vice-chairman has, however, been rejected. The workload has steadily increased over the past 10 years, from 66 protocols a year to 302. During a recent 12-month period, 277 research submissions were received; 143 of them were agreed without amendment, 93 with minor amendments, and 41 were rejected or required further information before they could be reconsidered. Assessment of outcome is more difficult. In future, the committee may ask for annual reports from investigators on their research and on any ethical problems encountered. Ethics committees need to foster good ethical research and inform researchers of ethical issues. Most of the latter are highlighted on the Leicestershire application form but are supplemented by short guidelines on particular topics. The committee consumes time and money; it is not clear if it will be adequately funded under the new NHS structure. PMID- 1588531 TI - Eurospeak. An explanatory note by the Department of Health. PMID- 1588532 TI - Pharmacovigilance. PMID- 1588533 TI - Application of immunological techniques to disease. PMID- 1588534 TI - The physician in the antenatal clinic. PMID- 1588535 TI - The arms of the college. PMID- 1588536 TI - Neurosyphilis yesterday and today. PMID- 1588537 TI - Neurosyphilis yesterday and today. PMID- 1588538 TI - Neurosyphilis yesterday and today. PMID- 1588539 TI - Quality of care with fewer junior doctors. PMID- 1588540 TI - Teaching rheumatology. PMID- 1588541 TI - Postcricoid web dysphagia. PMID- 1588542 TI - Systolic time intervals and their derivatives for evaluation of cardiac function. AB - Systolic time intervals provide a noninvasive indication of global left ventricular performance, are relatively sensitive, and are easily obtained from an M-mode echocardiogram. This paper defines systolic time intervals (preejection period, left ventricular ejection time, and total electromechanical systole) and their derivatives (preejection period/left ventricular ejection time and velocity of circumferential fiber shortening). Their utility and weaknesses, as well as the effects of heart rate, loading conditions, cardiac contractility, and drug therapies on systolic time intervals are discussed. Normal values for systolic time intervals for the dog and cat are provided. PMID- 1588543 TI - Effect of therapy on susceptibility to urinary tract infection in male cats with indwelling urethral catheters. AB - Indwelling urinary catheters with a closed urine collection system were maintained in 30 male cats for 3 days after induction of irritant cystitis. All cats received subcutaneous fluids during the 3 days the catheters were in place. The effects of four different treatment regimens on urinary tract infection rates, incidence of urethral obstruction, and development of urinary tract lesions over a 10-day period were compared with results in a nontreated group. Treatments were 1) amoxicillin for 5 days PO; 2) prednisolone for 5 days PO; 3) both amoxicillin and prednisolone for 5 days PO; and 4) dimethylsulfoxide (DMSO) for 3 days intravesicularly. Euthanasia was done before the end of the 10-day experimental period if the cats had two bouts of urethral obstruction or if the cats became uremic for causes unrelated to urethral obstruction. Seven cats were euthanatized before the conclusion of the experiment. These cats had been treated with prednisolone, prednisolone and amoxicillin, or DMSO. All cats that received amoxicillin alone or no therapy survived the 10-day period. Mortality was due to repeated urethral obstruction or to uremia associated with pyelonephritis or papillitis. Urinary tract infection rate was similar in all groups. The group treated with prednisolone alone had the highest incidence of renal infection. Inflammatory lesions in the lower urinary tract were similar in all groups. In conclusion, persistent urinary tract infection often develops in cats with cystitis after indwelling urethral catheterization even when closed systems of urine drainage are used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588544 TI - Ultrasonography of diffuse liver disease. A review. AB - Radiographically, the liver may appear normal even if severely diseased. Ultrasonography can be an important adjunct in the evaluation of diffuse parenchymal hepatic disease. Diffuse liver disease appears ultrasonographically as a change in liver echogenicity from normal when compared with the renal cortex or spleen. Diffuse liver disease can be characterized as either hyperechoic due to fatty change, steroid hepatopathy, and cirrhosis or hypoechoic due to congestion, suppurative hepatitis, and lymphoma. Ultrasonographic diagnosis of diffuse liver disease should be substantiated by biopsy and histopathologic evaluation. PMID- 1588545 TI - Treatment of membranoproliferative glomerulonephritis and nephrotic syndrome in a dog with a thromboxane synthetase inhibitor. AB - A 2-year-old spayed female Whippet with membranoproliferative glomerulonephritis and nephrotic syndrome was treated with a specific thromboxane synthetase inhibitor (3-methyl-2[3-pyridyl]-1-indoleoctanoic acid), resulting in decreased proteinuria and resolution of ascites and edema. Glomerular histology, however, appeared unaffected by treatment. Discontinuation of treatment for 10 weeks resulted in increased proteinuria and decreased serum albumin concentrations that were again attenuated when treatment was reinitiated. Thromboxane synthetase inhibitors have been used successfully to treat experimentally induced glomerulonephritis in several species and this treatment appears to hold promise for naturally occurring glomerulonephritis in dogs. PMID- 1588546 TI - Doxorubicin-induced cardiotoxicosis. Clinical features in 32 dogs. AB - Clinical cardiac abnormalities developed in 32 of 175 dogs that had various malignancies and were treated with doxorubicin: 31 dogs had electrocardiographic abnormalities including arrhythmias and nonspecific alterations in the R wave, ST segment, or QRS duration and 7 dogs had congestive heart failure. All seven dogs that had congestive heart failure died within 90 days. At necropsy, 13 of 32 affected dogs had noninflammatory myocardial degeneration, myocytolysis, vacuolation, and/or fibrosis and there was intramural coronary arteriosclerosis in all 13. Five dogs with lymphosarcoma were in complete clinical remission when they died of doxorubicin-induced cardiomyopathy, but the overall survival times of the lymphosarcoma subset was nevertheless longer than in previous studies. The clinical use of doxorubicin in the dog can cause cardiotoxicosis but the therapeutic benefit appears to outweigh risks in most dogs. PMID- 1588547 TI - Prognostic variables for survival of neonatal foals under intensive care. AB - The costly nature of intensive care for neonatal foals prompted a study of predictive variables for survival in a referral hospital. Applying stepforward logistic regression to parameters that differed significantly (P less than 0.10) between survivors (S) and nonsurvivors (NS) in a retrospective study (n = 56), two variables retained statistical significance [anion gap (AG, P = 0.0047) and venous PO2 (PvO2, P = 0.0342)], thus forming the basis for a predictive equation for survival: the Pn (probability of NS) = eA/(1 + eA) where A = -1.46 - 0.107 (PvO2) + 0.213 (AG). The predictive equation was evaluated prospectively in foals (n = 48), irrespective of diagnosis, that underwent intensive care. Sepsis was the most common medical problem identified in both groups of foals (51/104). In the prospective study, a Pn less than or equal to 0.5 predicted S (positive test) and Pn greater than 0.5 predicted NS (negative test). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the predictive equation were 100%, 40%, 62%, and 100%, respectively. All foals with Pn greater than 0.4 (n = 14) did not survive. Erroneous predictions were consistently false positives (predicted S, outcome NS). The predictive equation for survival may aid in identification of high risk neonates, i.e., unlikely to survive. The prognostic merits of anion gap and PvO2 imply that tissue oxygen debt was a significant problem for these critically ill foals. PMID- 1588548 TI - Carotid body tumors in the dog. Eleven cases (1978-1988). AB - Case records of 11 dogs with histologically confirmed carotid body tumors were reviewed. Surgical excision had been attempted in ten dogs with carotid body tumors, and one dog had been euthanatized at diagnosis. There were no intraoperative deaths but perioperative mortality was 40%. Horner's syndrome and laryngeal paralysis were the most common postoperative morbidities. The median survival time after surgery alone in the four dogs that survived the perioperative period was 25.5 months (range, 12-45 months). Two dogs treated with postoperative radiation therapy had survival times of 6 and 27 months. Of the six dogs surviving the perioperative period, two dogs are still alive at 19 and 32 months postoperatively. Of the four dogs that died, one was euthanatized 12 months postoperatively for nontumor-related causes. The remaining three dogs died of distant metastases. The carotid body tumors studied were characterized by local tissue invasion, neurovascular complications after therapy, and a propensity to metastasize to multiple sites in the body. PMID- 1588549 TI - Antiandrogenic steroidal sulfonyl heterocycles. Utility of electrostatic complementarity in defining bioisosteric sulfonyl heterocycles. AB - Complementarity of electrostatic potential surface maps was utilized in defining bioisosteric steroidal androgen receptor antagonists. Semiempirical and ab initio level calculations performed on a series of methanesulfonyl heterocycles indicated the requirement for a partial negative charge at the heteroatom attached to C-3 of the steroid nucleus to attain androgen receptor affinity. Synthesis and testing of six heterocycle A-ring-fused dihydroethisterone derivatives support this hypothesis, and we have identified two new androgen receptor antagonists of this class. PMID- 1588550 TI - Definition and display of steric, hydrophobic, and hydrogen-bonding properties of ligand binding sites in proteins using Lee and Richards accessible surface: validation of a high-resolution graphical tool for drug design. AB - The accessible surface, described by Lee and Richards (the L&R surface: J. Mol. Biol. 1971, 55, 379), has remarkably useful properties for displaying ligand protein interactions. The surface is placed one van der Waals radius plus one probe radius away from the protein atoms. The ligands are displayed in skeletal form. With a suitable probe radius, those parts of the ligand in good van der Waals contact with the protein binding site are found superimposed on the L&R surface. Display of the surface using parallel contours therefore provides a very powerful guide for interactive drug design because only ligand atoms lying on or close to the surface are in low-energy contact. The ability of the surface to accurately display steric complementarity between ligands and proteins was optimized using data from small molecule crystal structures. The possibility of displaying the chemical specificity of the binding site was also investigated. The surface can be colored to give precise information about chemical specificity. Electrostatic potential, electrostatic gradient, and distance to hydrogen-bonding groups were tested as methods of displaying chemical specificity. The ability of these methods to describe the complementarity actually observed in the interior of proteins was compared. High-resolution crystal data for ribonuclease and trypsin was used. The environment surrounding extended peptide chains in the protein was treated as a virtual binding site. The peptide chain served as a virtual ligand. This large sample of experimental data was used to measure the correlation between type of ligand atom and the calculated property of the nearest binding site surface. The best correlation was obtained using hydrogen-bonding properties of the binding site. Using this parameter the surface could be divided into three separate zones representing the hydrophobic, hydrogen-bond-acceptor, and hydrogen-bond-donor properties of the binding site. The percentage of hydrophobic ligand atoms found to lie closest to the hydrophobic protein surface was 91%. The equivalent scores for ligand hydrogen-acceptor atoms and hydrogen-donor atoms found at the corresponding complementarity zone were 94% and 91%. The surface zones can be readily displayed using three colors. To test the method on real ligand/binding site interactions, nine thermolysin-inhibitor complexes of known structure were evaluated using the parameters and criteria derived from the protein-packing study and a correlation between complementary contacts and logarithm of potency was obtained which had an r2 of 0.99.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588551 TI - Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1' phenyl substituents: X-ray crystal structure assisted design. AB - By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions. PMID- 1588552 TI - HIV-1 protease inhibitors based on hydroxyethylene dipeptide isosteres: an investigation into the role of the P1' side chain on structure-activity. AB - A systematic investigation was undertaken to determine the role of the P1' sidechain in a series of hydroxyethylene isostere based inhibitors of HIV-1 protease. Substitution and homologation of the benzyl P1' side chain of the Phe Phe isostere based pseudo peptides 1 (L-682,679) and 2 (L-685,434) with various heteroalkyl groups leads to a series of extremely potent inhibitors of the enzyme. Several examples of the most potent inhibitors were very effective in an ex vivo cell based viral spread assay using human H9 T-lymphocytes and the IIIb isolate of HIV-1. Compound 19 is 120 times more potent than 1 and 16 times more potent than 2 in inhibiting the spread of infection in this assay. PMID- 1588553 TI - 1,2,3-trisubstituted cyclopropanes as conformationally restricted peptide isosteres: application to the design and synthesis of novel renin inhibitors. AB - The 1,2,3-trisubstituted cyclopropanes 6 and 7 are the first members of a novel class of isosteric replacements for peptide linkages that are more generally represented by the dipeptide mimics 2 and 3. These unique peptide surrogates are specifically designed to lock a section of a peptide backbone in an extended beta strand conformation (phi-angle restriction) while simultaneously enforcing one of two specifically defined orientations for the amino acid side chain (chi 1-angle restriction). Methods were first developed for the stereoselective, asymmetric synthesis of the trisubstituted cyclopropanes 15a-d, 18a-d, 22a-d, and 23a-d (Scheme II), by an efficient approach featuring the Rh2(S-MEPY)4 (11) and Rh2(R MEPY)4 (20) catalyzed cyclization of the allylic diazoacetates 10a-d to give the optically active lactones 12a-d and 21a-d, respectively, in up to greater than or equal to 94% enantiomeric excess. Nucleophilic opening of the lactone ring of 12a d gave the corresponding morpholine amides 14a-d. By exploiting tactics that allowed for selective epimerization of one of the two functionalized side chains on the cyclopropane nucleus, 14a-d were transformed into the two series of diastereoisomeric morpholine amide carboxylic acids 15a-d and 18a-d. Epimerization of the morpholine amide group on 14a-d followed by Jones oxidation of the intermediate alcohols gave 15a-d. Alternatively, initial oxidation of the primary alcohol groups in 14a-d followed by selective, base-catalyzed inversion alpha to the aldehyde function and then Jones oxidation gave the diastereomeric dicarboxylic acid derivatives 18a-d. In a similar fashion, the enantiomeric lactones 21a-d were converted into the two corresponding enantiomeric series of dicarboxylic acid derivatives 22a-d and 23a-d. Inhibitors of aspartic proteinases, of which renin is a typical example, are known to bind to the enzyme active site cleft in an extended conformation. Thus, in order to evaluate the efficacy of 1,2,3-trisubstituted cyclopropanes as rigid replacements of beta strand secondary structure in pseudopeptidic ligands, 15a-d, 18a-d, 22a-d, and 23a-d were incorporated at the P3 subsite of the potential renin inhibitors 24a-h and 25a-h by coupling with the tripeptide replacement 8. A significant number of substances inhibited renin at nanomolar concentrations. On the basis of this preliminary test, 1,2,3-trisubstituted cyclopropanes do appear to constitute a viable new class of peptide mimics. Since the stereochemistry at each carbon on the cyclopropane ring may be altered, these novel replacements may also function as stereochemical probes to establish the conformation of pseudopeptide ligands bound to their macromolecular targets. PMID- 1588554 TI - Nonpeptide renin inhibitors employing a novel 3-aza(or oxa)-2,4-dialkyl glutaric acid moiety as a P2/P3 amide bond replacement. AB - A new series of renin inhibitors has been developed. The inhibitors feature a novel replacement for the P2/P3 dipeptide moiety normally associated with renin inhibitors. The dipeptide replacement was a (2S,4S)-3-aza(or oxa)-2,4 dialkylglutaric acid amide. Extensive structure-activity relationship studies determined that optimum potency was achieved when inhibitors employed a benzyl and butyl group at the C(4) and C(2) carbon position, respectively. In addition, maximum in vitro potency was obtained when the N-terminus was functionalized by incorporating a 4-(1,3-dioxabutyl)piperidine amide. SAR data suggested that the 1,3-dioxabutyl group (methoxymethyl ether) interacted by hydrogen bonding to groups in the S4 domain of renin. This hypothesis was strengthened when a 4 butylpiperidine amide was substituted and inhibitor potency decreased dramatically. Inhibitors employing this novel dipeptide mimic were prepared by coupling the glutaric acid amides with either the transition-state mimic (2S,3R,4S)-2-amino-1-cyclohexyl-3,4-dihydroxy-6- methylheptane (18) or the hydroxyethylene dipeptide isostere. The glutaric acid amides were prepared by two general procedures. The first procedure involved the reductive amination of alpha amino acid esters with alpha-keto esters. The second procedure involved the displacement reaction of alpha-bromo esters or acids with alpha-amino acid amides. PMID- 1588555 TI - C-terminal modifications of nonpeptide renin inhibitors: improved oral bioavailability via modification of physicochemical properties. AB - We describe the development of a series of soluble, potent, and bioavailable nonpeptide renin inhibitors. These inhibitors derived from a series of novel nonpeptide renin inhibitors which were recently identified in our laboratories, by alteration of the nature of the C-terminus (P2') of the molecules. Introduction of basic substituents into modified hydroxyethylene dipeptide isosteres gave inhibitors with improved solubility as well as improved potency against human plasma renin. In addition, these modifications produced inhibitors which displayed markedly improved intraduodenal bioavailability in both the ferret and cynomolgus monkey. We also present data which demonstrate excellent efficacy in the monkey for A-74273 (65), with an intraduodenal bioavailability of 16 +/- 4% in the monkey, compared to 1.7 +/- 0.5% for the dipeptide renin inhibitor enalkiren (A-64662, 75). A-74273 is an example of a nonpeptide inhibitor which possesses a good balance of the desirable properties of potency, solubility, and lipophilicity and which is well absorbed into the intestine. PMID- 1588557 TI - Structure-activity relationships of (+)-CC-1065 analogues in the inhibition of helicase-catalyzed unwinding of duplex DNA. AB - (+)-CC-1065 is a potent antitumor antibiotic produced by Streptomyces zelensis. Previous studies have shown that the potent cytotoxic and antitumor activities of (+)-CC-1065 are due to the ability of this compound to covalently modify DNA. (+) CC-1065 reacts with duplex DNA to form a (N3-adenine)-DNA adduct which lies in the minor groove of DNA overlapping with a five base-pair region. As a consequence of covalent modification with (+)-CC-1065, the helix bends into the minor groove and also undergoes winding and stiffening. In the studies described here, we have constructed templates for helicase-catalyzed unwinding of DNA that contain site-directed (+)-CC-1065 and analogue DNA adducts. Using these templates we have shown that (+)-CC-1065 and select synthetic analogues, which have different levels of cytotoxicity, all produce a significant inhibition of unwinding of a 3'-tailed oligomer duplex by helicase II when the displaced strand is covalently modified. However, the extent of helicase II inhibition is much more significant for (+)-CC-1065 and an analogue which also produced DNA winding when the winding effects are transmitted in the opposite direction to the helicase unwinding activity. This observed pattern of inhibition of helicase catalyzed unwinding of drug-modified templates was the same for a 3'-T-tail, for different duplex region sequences, and with the Escherichia coli rep protein. Unexpectedly, the gel mobility of the displaced drug-modified single strand was dependent on the species of drug attached to the DNA. Last, strand displacement by helicase II coupled to primer extension by E. coli DNA polymerase I showed the same pattern of inhibition when the lagging strand was covalently modified. In addition, the presence of helicase II on single-stranded regions of templates caused the premature termination of primer extension by DNA polymerase. These results are discussed from the perspective that (+)-CC-1065 and its analogues have different effects on DNA structure, and these resulting structural changes in DNA molecules are related to the different in vivo biological consequences caused by these drug molecules. PMID- 1588556 TI - Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1. AB - N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4 nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4 cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response. PMID- 1588558 TI - 4'-modified analogues of aristeromycin and neplanocin A: synthesis and inhibitory activity toward S-adenosyl-L-homocysteine hydrolase. AB - The carbocyclic adenosine analogues aristeromycin and neplanocin A both display significant S-adenosyl-L-homocysteine (AdoHcy) hydrolase inhibitory activity and broad-spectrum antiviral effects. Since phosphorylation of the 4'-hydroxymethyl substituent has been implicated with the cytotoxicity of these compounds, various analogues modified at this position were synthesized utilizing a key cyclopentenone intermediate 3 which can be derived from several members of the natural chiral pool. Cyclopentenone 3 underwent a highly stereoselective conjugate addition with organocuprate reagents, and the 1,4-adducts so formed were then readily elaborated to the corresponding 4'-modified aristeromycin analogues. Alternatively, quenching the enolate intermediate of the organocuprate conjugate addition with methanesulfinyl chloride followed by pyrolytic syn elimination resulted in the formation of 4'-modified neplanocin A intermediates. Three of the final compounds (1b, 1c, and 1e) displayed inhibitory activity toward AdoHcy hydrolase in the nanomolar range. PMID- 1588559 TI - Molecular modeling and crystallographic studies of 4-amino-N-phenylbenzamide anticonvulsants. AB - The molecular structures of five different MES-active N-phenylbenzamides were determined by X-ray diffraction methods, and the conformations of a series of active and inactive benzamides were analyzed by molecular mechanics calculations. The most active compounds adopt a similar, consistent conformation in both the experimentally determined crystallographic structures and in the calculated molecular mechanics structures. This conformation places one o-methyl group proximal to the NH group of the central amide plane and orients the methyl substituted phenyl ring at an angle of 90 degrees to 120 degrees to the central amide plane. Intermolecular interactions in the crystal structures indicate that hydrogen bonding to the central amide group is the important interaction. The observed consistent conformation facilitates formation of hydrogen bonds to the carbonyl oxygen atom. The conformations of inactive compounds obstruct this interaction. These findings help to outline a model of some of the structural features which this series of benzamides must possess in order to demonstrate MES anticonvulsant activity. PMID- 1588560 TI - Probes for the cocaine receptor. Potentially irreversible ligands for the dopamine transporter. AB - Several potentially irreversible ligands (i.e., wash-resistant binding inhibitors) for the cocaine receptor site on the dopamine transporter, derived from (-)-cocaine or 3 beta-phenyltropan-2 beta-carboxylic acid methyl ester (WIN 35,065-2), were prepared and shown to produce wash-resistant inhibition of [3H]-3 beta-(p-fluorophenyl)tropan-2 beta-carboxylic acid methyl ester ([3H]WIN 35,428) binding. All the compounds prepared had the same absolute configuration as cocaine; they include analogues possessing chemically reactive groups such as the isothiocyanato and bromoacetamido as well as photoactive azido groups. The potentially irreversible ligands, as well as all the intermediates prepared in this study, were evaluated for their ability to inhibit the binding of [3H]WIN 35,428 in coincubation experiments. Of the potentially irreversible ligands, 3 beta-(p-chlorophenyl)tropan-2 beta-carboxylic acid 2-[p (bromoacetamido)phenyl]ethyl ester (6c) had the highest apparent potency. The potentially irreversible ligands were also preincubated, and inhibition of [3H]WIN 35,428 binding was determined both before and after washing the ligand exposed tissues. The most effective ligands in this regard were 3 beta-(3-iodo-4 azidophenyl)tropan-2 beta-carboxylic acid methyl ester (5) and 3 beta-(p chlorophenyl)tropan-2 beta-carboxylic acid 2-(3-iodo-4-azidophenyl)ethyl ester (6d). The structure-activity relationships of these data are discussed. PMID- 1588561 TI - Dual-action penems and carbapenems. AB - Two new series of dual-action antibacterial agents were synthesized in which penems and carbapenems were linked at the 2'-position to quinolones through either an ester or a carbamate moiety. Potent, broad-spectrum antibacterial activity was observed for both classes of compounds, indicative of a dual-mode of action. PMID- 1588562 TI - Synthetic modification of a novel microbial ionophore: exploration of anticoccidial structure-activity relationships. AB - While fermentation-derived polyether ionophores such as salinomycin are the dominant class of anticoccidial feed additives, there is little information concerning the structural features which confer optimal potency/efficacy in this important series. The recently discovered microbial polyether 1a, featuring potent, broad-spectrum anticoccidial activity, was employed as a template to explore structure-activity relationships. A number of single-step synthetic modifications targeted structural changes in both the lipophilic carbon backbone and the ion-binding cavity of 1a. Although previous semisynthetic transformations among the polyether ionophores almost always resulted in a substantial loss of anticoccidial activity, we obtained several analogues, altered on the periphery of the ionophore-ion complex, which retain good potency and efficacy. Monoglycone 7 (semduramicin sodium) has the most impressive anticoccidial profile of this series, and is undergoing further biological testing under field conditions. PMID- 1588563 TI - Novel thiazolidine-2,4-diones as potent euglycemic agents. AB - A new series of thiazolidine-2,4-diones was obtained by replacing the ether function of englitazone with various functional groups, i.e., a ketone, alcohol, or olefin moiety. These compounds lower blood glucose levels in the genetically obese and insulin-resistant ob/ob mouse. Appending an oxazole-based group at the terminus of the chain provided highly potent compounds. PMID- 1588564 TI - Geiparvarin analogues. 3. Synthesis and cytostatic activity of 3(2H)-furanone and 4,5-dihydro-3(2H)-furanone congeners of geiparvarin, containing a geraniol-like fragment in the side chain. AB - Continuing our study on the structural features of geiparvarin (1), responsible for cytostatic activity, a series of 4,5-dihydro-3(2H)-furanones 10a-f and of 3(2H)-furanones 11a-f as well as 2",3"-dihydrogeiparvarin (14) have been designed and synthesized. Their cytostatic activity was evaluated against proliferation of murine (L1210, FM3A) and human (Raji, Molt/4F, and MT4) tumor cells. Modifications in the region of the olefinic double bond by introduction of the characteristic alkenyl side chain of ascofuranone (compounds 10a-f and 11a-f) markedly decreased the cytostatic activity as compared to geiparvarin itself, but this effect does not seem to be correlated to the presence of the furanone moiety linked to the alkenyl chain or to the ability to afford Michael type adducts. Replacement of the coumarin portion by other aromatic rings did not alter the cytostatic activity. The essential inactivity of 2",3"-dihydrogeiparvarin (14) points to the importance of the 3(2H)-furanone ring system in the cytostatic activity; consequently, this moiety may be considered as the determinant pharmacophore for antitumor activity, while the side chain plays a rather modulatory role. PMID- 1588565 TI - Synthesis and anti-HIV activity of 9-[c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r 1-yl]-9H-adenine. AB - The synthesis and in vitro anti-HIV activity of two new racemic nucleoside analogues are described; namely, 9-[c-4,t-5-bis(hydroxymethyl)cyclopent-2-en-r-1 yl]-9H-adenine (12) and its guanine analogue 18. While the latter (18) showed no activity, the therapeutic index of the former (12) was 200 and comparable to that (400) of carbovir. One enantiomer of 12 may be viewed as an analogue of carbocyclic oxetanocin and the other as an analogue of carbovir. Hence, these results indicate that one or both of the individual enantiomers of 12 could serve as candidates or lead compounds for the development of anti-AIDS agents. PMID- 1588566 TI - Substrate specificity of isopenicillin N synthase. AB - Highly purified isopenicillin N synthase (IPNS) from two sources (naturally occurring in Penicillium chrysogenum and that expressed in Escherichia coli via a cloned gene derived from Cephalosporium acremonium) have been isolated and utilized in vitro to test synthetic modifications of the natural substrate, (L alpha-amino-delta-adipyl)-L-cysteinyl-D-valine (ACV). A very sensitive procedure utilizing the ability of beta-lactams to induce the synthesis of beta-lactamase was employed to determine whether an ACV analogue could serve as a substrate for IPNS. A wide variety of amino and carboxyl terminal tripeptide substitutions were examined and found to elicit positive beta-lactamase induction profiles. However, none of these modifications were found to function as efficiently as a substrate as ACV. One of the beta-lactam products which was formed from the reaction of IPNS and the tripeptide analogue was independently synthesized and evaluated for antibacterial activity. Modification of the L-cysteine residue in the second position of ACV resulted in tripeptides that were unable to serve as substrates. Conversion of the D-valine residue in the third position of ACV to an aromatic amino acid or to a highly electronegative residue such as trifluorovaline resulted in elimination of substrate activity and creation of an inhibitor of the enzyme. PMID- 1588567 TI - Synthesis and pharmacological investigation of the enantiomers of muscarone and allomuscarone. AB - A strategy based on the use of (R)- and (S)-lactic ester as starting materials allowed the synthesis of the two enantiomers of muscarone [(-)-1 and (+)-1] and allomuscarone [(-)-5 and (+)-5] in greater than 98% enantiomeric excess. The compounds were examined for their ability to bind to membranes from cerebral cortex (M1), heart (M2), and salivary glands (M3) and to recognize affinity agonist states of the muscarinic receptors. The two pairs of enantiomers were also tested in five functional assays, and their muscarinic potency was determined. In both binding and functional tests, (-)-1 (2S,5S) and (-)-5 (2R,5S) were the eutomers of muscarone and allomuscarone, respectively. The eudismic ratio of muscarone, evaluated in the functional tests, spanned a range of 280 440. These values are substantially different from ones (2.4-10.1) reported in the literature. From a stereochemical point of view, muscarone behaves as muscarine and all other major muscarinic agonists; as a consequence, the hypotheses advanced to account for the anomalies of muscarone no longer have reason to exist. PMID- 1588568 TI - Bioreductive fluorescent markers for hypoxic cells: a study of 2-nitroimidazoles with 1-substituents containing fluorescent, bridgehead-nitrogen, bicyclic systems. AB - The oxygen-sensitive bioreductive binding of 2-nitroimidazoles labeled with fluorescent side chains has been used to stain hypoxic mammalian cells selectively. Several novel compounds were synthesized with a 1-substituent containing a fluorescent, bicyclic system having a bridgehead-nitrogen atom. Additional amine and secondary alcohol substituents were also included in the link between the fluorophor and the nitroimidazole to improve water solubility. Their ability to discriminate between hypoxic and oxic cells was compared by flow cytometric analysis. A wide range of cellular fluorescence and hypoxic-oxic differentials in fluorescence was observed when compounds with indolizine fluorophors were incubated with cells, and one such compound was considered suitable for further evaluation in vivo. Two compounds with bimane fluorophors gave very little cellular fluorescence when incubated with hypoxic cells. PMID- 1588569 TI - Ovarian toxicity of hexachlorobenzene (HCB) in the superovulated female rat. AB - Hexachlorobenzene (HCB) is a persistent environmental contaminant which has been measured in human serum, fat, semen, and follicular fluid. In animal testing HCB has been shown to be a reproductive toxin. Discrepant results were obtained from prior studies concerning the effect of HCB treatment on ovarian steroidogenesis. The current study was designed to assess the impact of HCB on the ovary and gonadal steroid levels in the superovulated rat. Female Sprague-Dawley rats (n = 24) were dosed with HCB (0.0, 1.0, 10.0, or 100.0 mg/kg BW/day) for 21 days. All rats received 10 IU pregnant mare serum gonadotropin (PMSG) s.c. on day 18 of treatment and 15 IU of human chorionic gonadotropin (hCG) on day 20. A terminal blood sample was collected and circulating levels of estradiol (E2) and progesterone. (P4) were determined. Serum concentrations of P4 were significantly (p less than 0.0034) elevated by HCB treatment at all dose levels. Ovarian weights were significantly increased (p less than 0.05) in the lowest dose group only compared to the control group. Serum concentrations of E2, uterine weight, weight gain, and general animal health were not affected by HCB treatment. We conclude that during HCB treatment the rat ovary remains responsive to gonadotropin stimulation. Moreover, it is suggested that HCB effects on ovarian steroidogenesis are indirect. PMID- 1588570 TI - Effect of N-methyl-N'-nitro-N-nitrosoguanidine on amino acid incorporation into mucosal protein of rat stomach. AB - Administration of the carcinogenic N-nitroso compound, N-methyl-N'-nitro-N nitrosoguanidine in drinking water (0.5 mg/mL) to male Wistar rats for 1 week caused impairment of in vivo and in vitro incorporation of [14C]leucine into stomach mucosal protein. This impairment gradually returned to normal after 4 weeks. Uptake of [14C]leucine into mucosal protein was significantly inhibited after in vitro treatment of stomach mucosa with the carcinogen. Addition of the N nitroso compound in a cell-free system using postmitochondrial supernatant prepared from stomach mucosa also showed inhibition of amino acid incorporation. Using a more defined system consisting of purified polyribosome from stomach mucosa and pH 5 enzyme fraction derived from liver it was further demonstrated that the carcinogen purturbed protein synthesizing ability of polyribosome, under both in vivo and in vitro treatment conditions. In these respects this carcinogen has similar action on the target tissue of stomach as in the liver, although the in vivo effect may be related more to toxicity than carcinogenicity. PMID- 1588571 TI - Lack of evidence for perfluorodecanoyl- or perfluorooctanoyl-coenzyme A formation in male and female rats. AB - Perfluorodecanoic (PFDA) and perfluorooctanoic (PFOA) acids belong to the structurally diverse group of compounds known to cause peroxisomal proliferation. It has been hypothesized that the common mode of action of these compounds is that they act through an activated coenzyme A (CoA) thioester. Using rat liver microsomal and isolated rat hepatocyte incubation conditions that were effective in producing a CoA conjugate of clofibric acid, no corresponding CoA derivative could be found for either PFDA or PFOA. PMID- 1588572 TI - Effect of endrin on the hepatic distribution of iron and calcium in female Sprague-Dawley rats. AB - The distribution of iron and calcium in hepatic subcellular fractions of female rats treated with endrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4 alpha,5,6,7,8,8 alpha- octahydroendo,endo-1,4:5,8-dimethanonaphthalene) was determined. Endrin in corn oil was administered orally to rats in single doses of 3, 4.5, or 6 mg/kg, and the animals were killed at 0, 12, 24, 48, or 72 hr post treatment. Iron and calcium were determined by atomic absorption spectroscopy. The administration of endrin increased the iron content of mitochondria and decreased the iron content of microsomes and nuclei. Significant increases occurred in the calcium content of mitochondria, microsomes, and nuclei. Thus, the results indicate that with respect to the subcellular distribution of iron and calcium, endrin produces differential effects. Vitamin E succinate administration partially prevented the endrin-induced hepatic alterations in iron and calcium homeostasis. Endrin also produced dose- and time-dependent increases in the liver and spleen weight/body weight ratios, while decreasing the thymus weight/body weight ratios. The altered distribution of calcium and iron may contribute to the broad range of effects of endrin. PMID- 1588573 TI - Regulation of two electrophoretically distinct proteins recognized by antibody against rat liver cytochrome P450 3A1. AB - We recently reported that antibody against purified P450 3A1 (P450p) recognizes two electrophoretically distinct proteins (50 and 51 kDa) in liver microsomes from male and female rats, as determined by Western immunoblotting. Depending on the source of the liver microsomes, the 51-kDa protein corresponded to 3A1 and/or 3A2 which could not be resolved by sodium dodecyl sulfate (SDS)polyacrylamide gel electrophoresis. The other protein (50 kDa) appears to be another member of the P450 IIIA gene family. Both proteins were markedly intensified in liver microsomes from male or female rats treated with pregnenolone-16 alpha carbonitrile, dexamethasone, troleandomycin, or chlordane. In contrast, treatment of male or female rats with phenobarbital intensified only the 51-kDa protein. Treatment of male rats with Aroclor 1254 induced the 51-kDa protein, but suppressed the 50-kDa form. In addition to their changes in response to inducers, the 50- and 51-kDa proteins also differed in their developmental expression. For example, the 50-kDa protein was not expressed until weaning (3 weeks), whereas the 51-kDa protein was expressed even in 1-week-old rats. At puberty (between weeks 5 and 6), the levels of the 50-kDa and 51-kDa proteins markedly declined in female but not in male rats, which introduced a large sex difference (male greater than female) in the levels of both proteins. Changes in the level of the 51-kDa protein were paralleled by changes in the rate of testosterone 2 beta-, 6 beta-, and 15 beta-hydroxylation. In male rats, the marked increase in the levels of the 50-kDa protein between weeks 2 and 3 coincided with a three- to four fold increase in the rate of testosterone 2 beta-, 6 beta-, and 15 beta-hydroxylation, which suggests that the 50-kDa protein catalyzes the same pathways of testosterone oxidation as the 51-kDa protein. However, this developmental increase in testosterone oxidation may have resulted from an activation of the 51 kDa 3A protein. These results indicate that the two electrophoretically distinct proteins recognized by antibody against P450 3A1 are regulated in a similar but not identical manner, and suggest that the 51-kDa 3A protein is the major microsomal enzyme responsible for catalyzing the 2 beta-, 6 beta-, and 15 beta hydroxylation of testosterone. PMID- 1588574 TI - Acrylonitrile interaction with testicular DNA in rats. AB - In the present study we report the in vivo interaction of acrylonitrile (VCN) with testicular tissue in rats. Covalent binding of radioactivity to testicular tissue DNA was examined for a period of 72 hr after a single oral dose (46.5 mg/kg) of [2,3-14C] VCN. Maximal covalent binding was observed at 0.5 hr (8.9 mumol VCN equivalent/mol nucleotide). Binding decreased gradually thereafter but was still detected (2.5 mumol VCN equivalent/mol nucleotide) at 72 hr following VCN administration. Further, we examined the effects of VCN on DNA synthesis and repair in the testes of rats following a single oral dose (46.5 mg/kg) of VCN to clarify the impact of the covalent binding observed on the testicular genetic material. A significant decrease in DNA synthesis (80% of control) was observed at 0.5 hr after treatment. At 24 hr following acrylonitrile administration, testicular DNA synthesis was severely inhibited (38% of control). Testicular DNA repair was increased 1.5-fold at 0.5 hr and more than 3.3-fold at 24 hr following treatment with VCN. These results suggest that VCN can act as a multipotent genotoxic agent by alkylating DNA in testicular tissue and may affect the male reproductive function by interfering with testicular DNA synthesis and repair processes. PMID- 1588575 TI - Evidence for the involvement of a distinct form of cytochrome P450 3A in the oxidation of digitoxin by rat liver microsomes. AB - The preceding paper (B. Gemzik, D. Greenway, C. Nevins, and A. Parkinson (1992). Regulation of two electrophoretically distinct proteins recognized by antibody against rat liver cytochrome P450 3A1. J. Biochem. Toxicol., 7 (43-52).) described the regulation of two rat liver microsomal proteins (50- and 51-kDa) recognized by antibody against P450 3A1. It was also shown that changes in the levels of the 51-kDa 3A protein were usually paralleled by changes in the rate of testosterone 2 beta-, 6 beta-, and 15 beta-hydroxylation. The present study demonstrates that age- and sex-dependent changes in the 50-kDa protein were paralleled by changes in the rate of digitoxin oxidation to digitoxigenin bisdigitoxoside. Induction or suppression of the 50-kDa protein by treatment of rats with various xenobiotics were also paralleled by changes in the rate of digitoxin oxidation. These results suggest that, contrary to previous assumptions, the conversion of digitoxin to digitoxigenin bisdigitoxoside and the conversion of testosterone to 2 beta-, 6 beta-, and 15 beta-hydroxytestosterone are primarily catalyzed by different forms of P450 3A. Further evidence for this conclusion was obtained from studies in which the suicide inhibitor, chloramphenicol, was administered to mature female rats previously treated with pregnenolone-16 alpha-carbonitrile (PCN), which induces both the 50-kDa and the 51-kDa protein. Treatment of mature female rats with PCN alone caused a marked increase (16- to 18-fold) in the 6 beta-hydroxylation of testosterone and the rate of digitoxin oxidation. Treatment of PCN-induced rats with chloramphenicol caused a approximately 70% decrease in liver microsomal testosterone 6 beta hydroxylation, but had no effect on the rate of conversion of digitoxin to digitoxigenin bisdigitoxoside. The oxidation of testosterone by purified 3A1 (a 51-kDa protein) was also inhibited by chloramphenicol in a time- and reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent manner. In addition to testosterone and chloramphenicol, purified 3A1 also metabolized troleandomycin, but it was unable to convert digitoxin to digitoxigenin bisdigitoxoside. Testosterone inhibited the microsomal oxidation of digitoxin, but digitoxin did not inhibit testosterone oxidation. This suggests that testosterone is a substrate for the 3A enzyme that metabolizes digitoxin, but that this form of P450 3A does not contribute significantly to testosterone oxidation by rat liver microsomes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588576 TI - PCR in the diagnosis of infectious disease. Proceedings of the Pathological Society of Great Britain and Ireland. London, January 8-10, 1992. PMID- 1588577 TI - Cyanobacteria and human health. PMID- 1588578 TI - Association of Vibrio cholerae with fresh water amoebae. AB - An investigation was undertaken to determine whether Acanthamoeba polyphaga SHI and Naegleria gruberi 1518/1e could affect the survival of various strains of Vibrio cholerae in laboratory microcosms. In microcosms pre-inoculated with trophozoites of amoebae, all six strains of V. cholerae tested survived and multiplied during 24 h. In control microcosms without trophozoites of amoebae, survival of the V. cholerae strains was much decreased. Two strains of V. cholerae were used to determine whether V. cholerae might survive ingestion within amoebae and subsequent encystment. Strain 152 was re-isolated from encysting N. gruberi 1518/1e but not from A. polyphaga SHI. Strain 9112 could not be isolated from cysts of either species of amoebae. PMID- 1588579 TI - Proteolytic activity of Clostridium difficile. AB - Ten isolates of Clostridium difficile expressing different degrees of toxigenicity and virulence in an animal model were assayed for the production of proteolytic enzymes by various methods. All strains demonstrated some activity in one or more of the assay systems. There was no direct correlation between toxigenic status and enzyme production. However, those strains known to be highly virulent in a hamster model were the most proteolytic. The most commonly detected enzyme was cell associated, and its substrate specificity suggested it was a trypsin-like enzyme. Initial purification of the enzyme from strain VPI 10463 gave a 10% yield with a 14-fold increase in purity. Inhibition studies on this preparation indicated that the enzyme was a thiol protease. The enzyme has pH and temperature optima of 7.5 and 37 degrees C, respectively. These characteristics suggest that the enzyme is more related to clostripain, the thiol clostridio peptidase of C. histolyticum, than to trypsin. Whilst the role of this enzyme remains unclear, it is possible that it may be a contributory factor in the virulence of the organism as described for other clostridial infections. PMID- 1588580 TI - Experimental rabbit model of meningitis produced by Haemophilus influenzae serotype c. AB - The virulence of Haemophilus influenzae type c when inoculated intracisternally (i.c.) into rabbits was evaluated. Rabbits are relatively resistant to infection with H. influenzae type b, such that inocula of the order of 10(6-9) cfu are required to produce meningitis in this model. In contrast, fatal meningitis was produced in this study when 10(3) cfu of a type-c strain were injected i.c. into rabbits. Numbers of bacteria in cerebrospinal fluid (CSF) of control (untreated) animals generally increased to 10(7) cfu/ml. Increases in white blood cells, protein and lactate in the CSF were similar to those which had been observed during meningitis due to Streptococcus pneumoniae in rabbits. The infection was amenable to therapy with ampicillin 50 mg/kg given intravenously 12 h after infection. Numbers of bacteria in CSF were reduced to 2.2 x 10(3) cfu/ml (SEM 0.2 x 10(3)) at 8 h after treatment with a single dose of ampicillin. Two doses of ampicillin, given 12 and 20 h after infection, significantly increased the mean survival time. In contrast to previous experimental studies with rabbits, the penetration of ampicillin into the CSF was high--46 (SEM 10) % of the blood level. Since considerable replication of H. influenzae type c occurred within the CSF in this model, the nature of the meningeal damage produced was likely to be similar to that which takes place in man. Hence, H. influenzae type c meningitis in rabbits may provide a useful model in which therapeutic and other experimental studies of H. influenzae meningitis can be performed. PMID- 1588581 TI - Neutrophil response to mucosal infection. AB - Total white cell counts were reviewed in paediatric in-patients with viral gastroenteritis, bacterial gastroenteritis, delayed recovery following acute gastroenteritis, viral lower respiratory tract infections and cow's milk protein intolerance. The prevalence of neutrophilia was not different in the five groups. Neutropenia was common in association with the presence of viruses in stool or sputum, and was significantly more common in these groups than in patients with bacterial gastroenteritis and cow's milk protein intolerance. Neutropenia has not been previously reported in viral gastroenteritis. It was transient in nature and not related to age, sex, weight or antibiotic treatment; no pancreatic disorders were noted. PMID- 1588582 TI - An epidemiological assessment of coagulase-negative staphylococci from an intensive care unit. AB - Detection of an unusual combination of four resistance markers among coagulase negative staphylococci (CNS) isolated in the same intensive care unit led to the undertaking of an epidemiological assessment. Seventeen CNS isolates from the same unit and 38 epidemiologically unrelated Staphylococcus epidermidis isolates were typed by eight methods, including analysis of immunoblot patterns and hybridisation patterns (HP) obtained with three probes. The probes comprised plasmids carrying the genes encoding 16S rRNA (pBA2), aacA-aphD (pSF815A), and aacA-aphD with part of IS256 (pIP1307). Immunoblot patterns and HP with pIP1307 indicated that 14 of the 17 CNS isolates from the same unit resulted from the spread of an epidemic strain. PMID- 1588583 TI - The accumulation of bactericidal lipids in staphylococcal abscesses. AB - Abscesses were generated in the peritoneal cavity of mice by the inoculation of 10(9) staphylococci. Abscess weight increased rapidly, reaching about 200 mg by the fourth day; for the next 60 days, abscess weight increased only slightly. The amount of total lipid increased during abscess development, attaining a peak level of about 19 mg per abscess at 7 days before decreasing. Almost all of this lipid resulted from the accumulation of neutral lipids. The small increases seen in the phospholipid and glycolipid fractions could be accounted for through the accumulation of host cellular elements in the abscess. Leucocytes containing cytoplasmic lipid droplets were first seen 4-12 h after infection and these cells were widely scattered around the periphery. During the next 2 days, the number of cells with lipid droplets increased markedly and lipid droplets were also found in the deeper portions of the abscesses. Although lipid droplets were found subsequently throughout the abscess, the greatest amounts always occurred in the leucocyte zone immediately proximal to the connective tissue capsule. During abscess development, the bactericidal activity also increased rapidly, reaching a maximum by the seventh day and declining thereafter. PMID- 1588584 TI - Effect of capsulation on the resistance of Staphylococcus aureus to the bactericidal lipids produced in abscesses. AB - Staphylococcus aureus strains differ in their sensitivity to some of the bactericidal lipids produced by the host in staphylococcal abscesses. To evaluate whether the presence of a capsule might account for these differences, capsulate and non-capsulate S. aureus strains were compared for their sensitivity to staphylococcal abscess homogenates and the neutral lipid fraction derived from such material. Although the presence of a capsule appeared to reduce sensitivity, two non-capsulate mutants were only about three-to-four times more sensitive than their capsulate parent strains. Another strain, known for its resistance to these bactericidal lipids, was not capsulate. This suggests that mechanisms other than capsule formation must also determine sensitivity to the lipids. PMID- 1588585 TI - Immunoblotting patterns with Mycoplasma pneumoniae of serum specimens from infected and non-infected subjects. AB - Two hundred and ninety-four serum specimens from 248 subjects, whose complement fixation (CF) titres to Mycoplasma pneumoniae were known, were further investigated by IgG immunoblotting. After analysis of M. pneumoniae proteins by SDS-PAGE, nine polypeptides (p) with mol. wts of 180-43 Kda were selected for immunoblotting studies. Antibodies to M. pneumoniae measured by immunoblotting appeared progressively with age; most subjects more than 19 years old gave positive results. For most of the polypeptides, there was an increase in the frequency of band detection when the CF titres were higher. Furthermore, paired serum specimens from 10 patients with M. pneumoniae infection, as demonstrated by a rise in CF antibody titre, were tested for IgG blotting patterns. Generally, p180 (the P1 adhesin of M. pneumoniae), p172 and p84 were shown to be the dominant targets of the immune response to this organism and may have diagnostic value. PMID- 1588586 TI - Immune response to Giardia lamblia in a water-borne outbreak of giardiasis in Sweden. AB - In one of the largest outbreaks of waterborne giardiasis reported from Europe, more than 3000 persons were exposed to contaminated water and over 1400 cases of giardiasis were diagnosed by microscopy. The outbreak resulted from an overflow of sewage water into the drinking water system of a Swedish ski resort. The period of contamination was about 1 week. Sweden is a non-endemic area for Giardia lamblia infection and, for most individuals affected, this was their first contact with the parasite. Few other enteropathogens were isolated from the patients involved. Therefore, an immune response to Giardia was unlikely to be biased by other concomitant infections. Serum samples from 352 exposed persons were collected and analysed for specific IgG and IgA antibodies to G. lamblia by indirect immunofluorescence and the results were related to the microscopic examination of faeces and the occurrence of diarrhoea. As controls, sera from 428 healthy persons were analysed at the same time by identical methods. IgG or IgA antibodies, or both, were found in 68% of patients whose diagnosis was made by microscopy, and in 22% of exposed by microscopically Giardia-negative persons, but in only 10% of healthy controls. The findings show that patients reported as negative for parasites might be infected. The time between infection and blood sampling influenced the result of the antibody test. The results suggest that stool examination should be the primary means of diagnosis of G. lamblia infection and that serological analysis performed at least 3 weeks after infection could contribute to diagnosis in a non-endemic region, when giardiasis is suspected but the parasite has not been detected. PMID- 1588588 TI - An ultrastructural study of differentiation of pyriform cells and their contribution to oocyte growth in representative squamata. AB - An electron microscopic study of the differentiation of pyriform cells and their contribution to oocyte growth in three lizards (Tarentola mauritanica, Cordylus wittifer, Platysaurus intermedius) and one colubrid snake (Coluber viridiflavus) revealed that pyriform cells differentiate from small follicle cells via intermediate cells after establishing an intercellular bridge with the oocyte (see also Hubert: Bull Soc Zool Fr 102:151-158, 1977; Filosa et al: J Embryol Exp Morphol 54:5-15 1979; Klosterman: J Morphol 192:125-144, 1987). Once differentiated, pyriform cells display ultrastructural features indicative of synthetic activity, including abundant ribosomes, Golgi membranes, vacuoles, mitochondria, and lipid droplets. These cellular components extend to the apex of the cell at the level of the intercellular bridge, suggesting that constituents of pyriform cells may be transferred to the oocyte. Furthermore, we demonstrate for the first time that pyriform cells incorporate exogenous yolk. The yolk is segregated inside maturing yolk granules that form in the pyriform cell in the same manner as described for vitellogenic oocytes in non-mammalian vertebrates (see Wallace: Developmental Biology, A Comprehensive Synthesis 127-177, 1985). It is the first clear evidence that pyriform cells and the oocyte may fulfill similar vitellogenic functions. The establishment of an intercellular bridge may represent a crucial event in the development of an integrated system in which pyriform cells and oocyte cooperate. PMID- 1588587 TI - Production and characterisation of mouse monoclonal antibodies reactive with the lipopolysaccharide core of Pseudomonas aeruginosa. AB - Monoclonal antibodies (MAbs) to the core antigen region of lipopolysaccharide (LPS) of Pseudomonas aeruginosa were produced from mice immunised with whole cells of heat-killed rough mutants of Pseudomonas aeruginosa expressing partial or complete core LPS. MAbs were screened in an enzyme-linked immunosorbent assay (ELISA) against three different antigen cocktails: S-form LPS from three P. aeruginosa strains, R-form LPS from six P. aeruginosa strains and, as a negative control, R-form LPS from Salmonella typhimurium and Escherichia coli. Selected MAbs were subsequently screened against a range of extracted LPS and whole cells from both reference strains and clinical isolates of P. aeruginosa. The antibodies were also screened in ELISA against whole-cell antigens from other Pseudomonas spp. as well as strains of Haemophilus influenzae, Neisseria subflava and Staphylococcus aureus. Five MAbs reacting with the core component of P. aeruginosa LPS were finally selected. Two of these, MAbs 360.7 and 304.1.4, were particularly reactive in immunoblots against unsubstituted core LPS, including that from O-antigenic serotypes of P. aeruginosa. The MAbs also reacted with some of the other Pseudomonas spp., but not with P. cepacia or Xanthomonas (Pseudomonas) maltophilia. Cross-reactivity with whole cells from other bacterial species was minimal or not observed. Reactivity of MAbs with some Staph. aureus strains was observed, and binding to the protein A component was implicated. The reactivity of the MAbs was investigated further by flow cytometry and immunogold electronmicroscopy. The suitability of the MAbs for an immunological assay for detection of P. aeruginosa in respiratory secretions from CF patients is discussed. PMID- 1588589 TI - The composite structure of quail pectoralis muscle. AB - The twitch fibers of the quail pectoralis muscle were found to have one neuromuscular junction each, located in the middle third of the fiber. The length of isolated fibers varied between 8.8 and 33.2 mm, with mean and median values of 16 and 15.6 mm, respectively. The lengths of the fascicles from which the fibers were isolated varied between 30 and 51 mm. The muscle fibers taper at both ends. The neuromuscular junctions, revealed after histochemically reacting the intact muscle for acetyl cholinesterase activity, were arranged in discrete bands, separated by intervals of between 0.94 and 6.70 mm, with a mean value of 3.14 mm. The quail pectoralis muscle is thus composed of discontinuous, tapered muscle fibers, arranged in an overlapping series. It is therefore a muscle in which tension is transmitted laterally between muscle fibers. PMID- 1588590 TI - Patterns of peripheral innervation of the tongue and hyobranchial apparatus in caecilians (Amphibia: Gymnophiona). AB - The innervation of the musculature of the tongue and the hyobranchial apparatus of caecilians has long been assumed to be simple and to exhibit little interspecific variation. A study of 14 genera representing all six families of caecilians demonstrates that general patterns of innervation by the trigeminal, facial, glossopharyngeal, and vagus nerves are similar across taxa but that the composition of the "hypoglossal" nerve is highly variable. Probably in all caecilians, spinal nerves 1 and 2 contribute to the hypoglossal. In addition, in certain taxa, an "occipital," the vagus, and/or spinal 3 appear to contribute fibers to the composition of the hypoglossal nerve. These patterns, the lengths of fusion of the contributing elements, and the branching patterns of the hypoglossal are assessed according to the currently accepted hypothesis of phylogenetic relationships of caecilians, and of amphibians. An hypothesis is proposed that limblessness and a simple tongue, with concomitant reduced complexity of innervation of muscles associated with limbs and the tongue, has released a constraint on pattern of innervation. As a consequence, a greater diversity and, in several taxa, greater complexity of neuroanatomical associations of nerve roots to form the hypoglossal are expressed. PMID- 1588591 TI - Histology of the reproductive tract of hybrids between gonochoristic males and parthenogenetic females of Lepidodactylus lugubris in French Polynesia (Reptilia, Gekkonidae). AB - Parthenogenetic populations of the gecko Lepidodactylus lugubris are widespread throughout Polynesia. They often occur parapatrically, and occasionally syntopically, with the increasingly rare bisexual populations. In these instances, a small number of hybrid individuals occur and include both "female" and "male" external phenotypes, both with greatly reduced gonads. Histological examination demonstrates that these hybrids possess small ovotestes. The differentiation of the cortical tissue is identical in both "male" and "female" hybrids, but the medullary tissue is more developed in "males." The remainder of the genital tract in "females" resembles that of fertile females in the parthenogenetic and bisexual populations. By contrast, the "male" hybrids are markedly intersexual. In one of the two specimens autopsied, the hemipenes are more or less the same size as those of bisexual males, and the sexual segment of the kidney is hypertrophied and serous. In the other hybrid "male," the hemipenes have a structure similar to that seen in females, and the sexual segment of the kidney is poorly differentiated. In both hybrid "males," the ductus deferens is extremely narrow and further reduced in its middle portion; oviducts are present and resemble those of normal or hybrid females. Thus, embryonic-like gonads are associated with complete and normal female reproductive ducts in hybrid "females." Hybrid "males" also have embryonic-like gonads and feminized genital ducts but associated with secondary sexual characters that match those of sexually active or quiescent normal males. PMID- 1588592 TI - Functional stages in the interrenal cells of Rana perezi (Anura: Ranidae). AB - The electron density of the lipid droplets and mitochondrial matrix of the interrenal cells of Rana perezi differs during the year. This makes it possible to characterize the different stages of interrenal cell activity. A droplet/mitochondria index, based on their relative size, may provide an indicator of cellular activity. PMID- 1588593 TI - Figures of Eberth in the amphibian larval epidermis. AB - Figures of Eberth are prominent extensive filamentous structures in the basal epidermal cells of larval amphibians. They are compared and contrasted qualitatively and quantitatively in a number of species of the three groups of living amphibians. Fully developed Figures consist of massive skeins of tonofilaments oriented in three dimensions and hinged on hemidesmosomes within the cell. The overall appearance of the Figures is similar in anurans, urodeles and Ichthyophis among the apodans. However, in terms of size and number per unit length of the proximal cell margin, the hemidesmosomes and the thickness or their emergent skeins in anurans and Ichthyophis differ significantly from those parameters in urodeles, a feature that is presumably independent of cell size. Figures are poorly developed or missing in embryos of Typhlonectes, which has no larval stage in its life history. These ubiquitous skeletogenous structures in the aquatic larval amphibians, among other things, could be protective of underlying delicate tissues and act as a stabilizer in bodily movement during swimming. They could also serve as a reserve of cytokeratin for use during later cellular division and sloughing. PMID- 1588594 TI - The influence of nearest neighbors on the rate and pattern of spontaneous point mutations. AB - The numbers and local sequence environments of the two types of substitution mutation plus additions and deletions have been obtained directly in this study from differences between a large number of extant primate gene and pseudogene sequences. A total of 3786 mutations were scored in regions where similarities between pseudogene and corresponding gene sequences is greater than or equal to 85%, comprising approximately 30% of the pseudogene database of 80,584 bp. The pattern of mutations obtained in this fashion is almost identical to that obtained by Li et al. (1984) using a slightly different, more direct approach and with a smaller database. When mutations were scored, the neighbor pairs on the 5' and 3' sides were also noted, leading to a large 16 x 12 matrix of transitions and transversions. Biases of varying magnitude are found in the rates of substitution of the same base pair in different local sequence environments. The overall order for the effect of the 5' neighbor on the rates of substitution mutation of a pyrimidine is A greater than C much greater than T greater than G, and G greater than A greater than T greater than C for the 3' neighbor; where these results represent the average of substitution rates for the complement purine with complement neighbors of bases ordered above. The order for the 3' neighbor is essentially the same for the two transitions and most of the four transversions as well; however, the order for the 5' neighbor is more variable. The overall rate for the C.G----T.A transition is not unusual, however the presence of a 3' neighboring G.C pair boosts the rate substantially, presumably due to specific cytosine methylation of the CG doublet in primate DNAs. The rate of the T.A----C.G transition is also well above average when the 3' neighbor is an A.T, and to a lesser extent a G.C, pair. The latter bias is typical in that it reflects the association of alternating pyrimidine-purine sequences with increasing mutation rates. The substitution of the pyrimidine in a 5'purine pyrimidine-purine3' sequence generally occurs much faster than in a pyrimidine tract and points to the local conformation as a major determining factor of the substitution rate. An apparent inverse relationship is found between starting and product doublet frequencies of base pairs undergoing mutations with specific 3' neighbors, indicating that differences in intrinsic substitution rates of base pairs with specific neighbors are a key factor in producing the familiar biases of nearest-neighbor frequencies. PMID- 1588595 TI - Evolution of the common cetacean highly repetitive DNA component and the systematic position of Orcaella brevirostris. AB - The common cetacean highly repetitive DNA component was analyzed with respect to its evolution and value for establishing phylogenetic relationships. The repeat length of the component, which is tandemly organized, is approximately 1750 bp in all cetaceans except the delphinids, in which the repeat length is approximately 1580 bp. The evolution of the component was studied after sequencing the component in different odontocetes representing the Delphinidae (delphinids), Monodontidae (narwhals), and Ziphiidae (beaked whales). The evolution of this component is very slow, and comparisons showed that sequence divergence among species corresponds closely to their generally accepted phylogenetic relationships and that the component evolves in a concerted manner. The phylogenetic information obtained in this study identified the Irrawaddy dolphin (Orcaella brevirostris) as a delphinid and did not support a close relationship of this species with the Monodontidae. PMID- 1588596 TI - Crypthecodinium and Tetrahymena: an exercise in comparative evolution. AB - Nucleotide sequences have been determined for the highly variable D2 region of the large rRNA molecule for over 60 strains of dinoflagellates. These strains were selected from a worldwide collection that represents all the known sibling species (compatibility groups, Mendelian species) in the sibling swarm referred to as Crypthecodinium cohnii. A phylogenetic tree has been constructed from an analysis of the variations in a length of about 180 bases, using PHYLOGEN string analysis programs. The Crypthecodinium tree is compared with the previously published but here augmented tree constructed upon the same rRNA region for the sibling species of a worldwide collection of ciliated protozoa related to the genus Tetrahymena. The first reported sequence of Lambornella clarki, the parasite of tree-hole mosquitoes, is included. The dinoflagellate species complex is much more homogeneous with respect to ribosomal variation. The mean number of differences among sequences from different Crypthecodinium species is about 7, in comparison with 22 differences among the ciliate species examined. Moreover, all the diversity in the dinoflagellates can be explained by base substitutions, whereas insertions and deletions are common in the ciliates. The dinoflagellates are also much more uniform with respect to nutritional and genetic economies. The two complexes differ also in the relationship between molecular variations and breeding compatibility. All tetrahymenine sibling species thus far examined are monomorphic in the D2 region, but several dinoflagellate species are polymorphic. Several different dinoflagellate species, moreover, have identical D2 regions. This kind of ribosomal identity of incompatible strains is found in these ciliates only in one tight cluster of species--Group C. The tetrahymenine swarm is apparently much older than the Crypthecodinium swarm, and the dinoflagellate species produce incompatible progeny species much more readily than do the ciliates, perhaps by the acquisition of mutations that potentiate incompatibility in sympatric populations. PMID- 1588597 TI - Sequence, proposed secondary structure, and phylogenetic analysis of the chloroplast 5S rRNA gene of the brown alga Pylaiella littoralis (L.) Kjellm. AB - The chloroplast 5S rRNA gene of the brown alga Pylaiella littoralis (L.) Kjellm has been cloned and sequenced. The gene is located 23 bp downstream from the 3' end of the 23S rRNA gene. The sequence of the gene is as follows: GGTCTTG GTGTTTAAAGGATAGTGGAACCACATTGAT CCATATCGAACTCAATGGTGAAACATTATT ACAGTAACAATACTTAAGGAGGAGTCCTTTGGGAAGATAGCTTATGCCTAAGAC. A secondary structure model is proposed, and compared to those for the chloroplast 5S rRNAs of spinach and the red alga Porphyra umbilicalis. Cladograms based on chloroplast and bacterial 5S rRNA and rRNA gene sequences were constructed using the MacClade program with a user-defined character transformation in which transitions and transversions were assigned unequal step values. The topology of the resulting cladogram indicates a polyphyletic origin for photosynthetic organelles. PMID- 1588599 TI - Codon usage in pathogenic Entamoeba histolytica. PMID- 1588598 TI - Genetic code and phylogenetic origin of oomycetous mitochondria. AB - We sequenced the 3'-terminal part of the COX3 gene encoding cytochrome c oxidase subunit 3 from mitochondria of Phytophthora parasitica (phylum Oomycota, kingdom Protoctista). Comparison of the sequence with known COX3 genes revealed that UGG is used as a tryptophan codon in contrast to UGA in the mitochondrial codes of most organisms other than green plants. A very high AT mutation pressure operates on the mitochondrial genome of Phytophthora, as revealed by codon usage and by A+T content of noncoding regions, which seems paradoxical because AT pressure causes tryptophan codon reassignment from UGG to UGA in mitochondria of most species. The genetic code and other data suggest that mitochondria of Oomycota share a direct common ancestor with mitochondria of plants and that mitochondria of the ancestor of Planta and Oomycota were acquired in a second endosymbiotic event, which occurred later than the acquisition of mitochondria by other eukaryotes. PMID- 1588600 TI - Involvement of lipid peroxidation in CNS injury. AB - The generation of oxygen radicals and the process of lipid peroxidation have become a focus of attention for investigators in the fields of central nervous system (CNS) injury and stroke (e.g., ischemia). While absolute proof for their involvement in the pathophysiology of traumatic and ischemic damage to the CNS remains to be established, numerous recent studies have provided considerable support for the occurrence of free radical and lipid peroxidation reactions in the injured or ischemic CNS. Furthermore, the use of antioxidants and free radical scavengers in the treatment of experimental and clinical CNS trauma and ischemia has provided convincing support for the involvement of oxygen radicals and lipid peroxidation in these conditions. In this report we will review some of the history behind the hypothesis for an involvement of oxygen radical-mediated lipid peroxidation in the pathophysiology of CNS injury and look at some of the more recent work conducted in this area. PMID- 1588601 TI - Demyelination in spinal cord injury and multiple sclerosis: what can we do to enhance functional recovery? AB - Demyelination in white matter tracts has been observed in experimental and human spinal cord injury. The pathophysiology of demyelinated axons depends, in part, on their ion channel organization. Myelinated axons display a complementary distribution of sodium channels (clustered in the nodal axon membrane) and fast potassium channels (in the internodal axon membrane). The low density of sodium channels in the internodal axon membrane will impede conduction after demyelination. Moreover, "unmasked" potassium channels will tend to clamp the axon membrane close to EK, interfering with conduction in demyelinated axons. Pharmacologic blockade of these potassium channels can increase the safety factor for conduction in demyelinated axons. Restoration of conduction in demyelinated axons, so that action potentials can traverse the zone without myelin, appears to underly clinical remissions in patients with multiple sclerosis and may occur in some patients with spinal cord injury. At a cellular level, conduction through demyelinated axon regions can be facilitated by several mechanisms, including remyelination, development of excitability in demyelinated regions (which requires an adequate density of sodium channels), and impedance matching. Astrocytes have been shown to establish a specific relationship with sodium channel-rich regions of the axon membrane, and may play a role in the deployment and/or maintenance of sodium channels within the demyelinated axon membrane. Calcium influx appears to play a critical role in the cascade of events leading to secondary injury after spinal cord trauma. Recent observations suggest the hypothesis that myelin damage in spinal cord trauma may be mediated, at least in part, by influx of calcium into an intracellular compartment. As the route of calcium entry is identified and characterized, it may be possible to design strategies that will limit secondary injury after CNS trauma. The deleterious effects of calcium in injured white matter accumulate gradually, which suggests the potential reversibility of dysfunction in spinal cord tracts if treated early after trauma. PMID- 1588602 TI - Potential of adult mammalian lumbosacral spinal cord to execute and acquire improved locomotion in the absence of supraspinal input. AB - The neural circuitry of the lumbar spinal cord can generate alternating extension and flexion of the hindlimbs. The hindlimbs of adult cats with complete transection of the spinal cord at a low thoracic level (T12-T13) can perform full weight-supporting locomotion on a treadmill belt moving at a range of speeds. Some limitations in the locomotor capacity can be associated with a deficit in the recruitment level of the fast extensors during the stance phase and the flexors during the swing phase of a step cycle. The level of locomotor performance, however, can be enhanced by daily training on a treadmill while emphasizing full weight-support stepping and by providing appropriately timed sensory stimulation, loading, and/or pharmacologic stimulation of the hindlimb neuromuscular apparatus. Furthermore, there appears to be an interactive effect of these interventions. For example, the maximum treadmill speed that a spinal adult cat can attain and maintain is significantly improved with daily full weight-supporting treadmill training, but progressive recruitment of fast extensors becomes apparent only when the hindlimbs are loaded by gently pulling down on the tail during the stepping. Stimulation of the sural nerve at the initiation of the flexion phase of the step cycle can likewise markedly improve the locomotor capability. Administration of clonidine, in particular in combination with an elevated load, resulted in the most distinct and consistent alternating bursts of electromyographic activity during spinal stepping. These data indicate that the spinal cord has the ability to execute alternating activation of the extensor and flexor musculature of the hindlimbs (stepping) and that this ability can be improved by several interventions such as training, sensory stimulation, and use of some pharmacologic agents. Thus, it appears that the spinal cord, without supraspinal input, is highly plastic and has the potential to "learn," that is, to acquire and improve its ability to execute full weight-supporting locomotion on a treadmill belt. PMID- 1588603 TI - Spinal cord injury models. AB - Spinal cord injury models continue to be used to learn more about the pathophysiology of injury as well as potential therapeutic interventions. Most researchers now rely on rat models of injury with injury produced by impact, compression, or even photochemical techniques. A number of laboratories have confirmed that reproducible and graded injury can be produced in the rat with outcome monitored by behavioral, neurophysiologic, and morphologic analyses. Biochemical, physiologic, and pharmacologic studies with these models are being used to further define factors that contribute to chronic injury and thus may be the subject of therapeutic intervention. In addition, a new approach to therapy is being explored via implantation of cells into the injured spinal cord. Cell suspensions can be implanted in clinically relevant injury models without exacerbating the effects of injury and with some indications of beneficial effect. The potential usefulness of such an approach is just beginning to be evaluated. PMID- 1588604 TI - Experimental models for spinal cord injury research: physical and physiological considerations. AB - This paper describes historical and current experimental models used to develop our current understanding of the biomechanics and pathophysiology of traumatic spinal cord injury; the advantages and limitations of current experimental models; considerations for selecting an appropriate injury model based on experimental objectives; and key physiological factors in the spinal cord injury response that may interact with the injury response and alter the outcome. All of the above must be considered in the development and selection of an appropriate experimental injury model that meets specific needs. Various experimental models have been developed to study spinal cord injury and the pathophysiological and physical mechanisms responsible for tissue damage and loss of function. Such modeling may involve inherently different biomechanical variables with alternative outcomes and purposes. There is not, therefore, a single "ideal" experimental injury model just as there is no "stereotypical" clinical spinal cord injury. Instead, the goals and objectives of the research dictate specific requirements on the model. In all cases, however, both physical and physiological aspects of the model should be considered, and measured if possible, to ensure interlaboratory comparability and possible clinical relevance. Also, experimental techniques, especially anesthesia, and surgical procedures, should be carefully reviewed for interactions with the injury response or potential therapeutic interventions to ensure validity of interpretation. It is hoped that data correlating physical spinal cord injury parameters with functional outcome will ultimately be combined with data on vertebral injury and spinal failure mechanics to further our understanding of clinical injury. Such approaches should lead to interventions that reduce the incidence and severity of traumatic human spinal cord injury. PMID- 1588606 TI - Evidence for free radical mechanisms of brain injury resulting from ischemia/reperfusion-induced events. AB - Free radicals have been implicated in the injury that occurs to brain tissue in response to ischemia and reperfusion insults. Confirmatory in vivo studies have been limited by the difficulty in measuring free radicals in brain tissue. This review discusses potential mechanisms for free radical production in brain tissue and the evidence supporting the therapeutic efficacy of free radical scavengers. Free radicals may be produced during ischemia/reperfusion as a result of multiple mechanisms involving normal regulatory systems of intra-/extracellular metabolism. For example, metabolism of free fatty acids by the cyclo-oxygenase pathway and adenine nucleotides by xanthine oxidase has been proposed to produce free radical adducts during reperfusion. Therapeutic strategies aimed at decreasing brain injury from free radical production include administration of free radical scavengers at the time of reperfusion. Pharmacologic interventions for protection from free radical injury in brain are hindered because of limited access to the site of free production. PMID- 1588605 TI - Cerebral cardiovascular and respiratory variables after an experimental brain missile wound. AB - Brain missile wounding (BMW) affects brainstem and medullary cadiorespiratory functions leading to immediate systemic hypertension, bradycardia, and apnea. Secondary complications may also occur because of subsequent changes in systemic and intracranial physiological variables. To delineate the immediate and secondary effects of BMW, we monitored changes in several cerebral and cardiorespiratory parameters in pentobarbital-anesthetized spontaneously breathing cats before wounding and up to 90 min afterward. Total and regional cerebral blood flow (rCBF) and cardiac output (CO) were measured (microsphere technique) and arterial blood was sampled for pH, PO2 and PCO2 once before BMW and one to four times afterward. Mean arterial blood pressure (MABP), intracranial pressure (ICP), cerebral perfusion pressure (CPP = MABP - ICP), electrocardiogram (ECG), heart rate (HR), and electroencephalogram (EEG) were continuously recorded. Respiratory frequency (f), tidal volume (Vt), and ventilation (V) were recorded during each flow measurement and periodically throughout the experiment. Four unwounded cats served as controls and 15 cats were wounded at 1.4 J fronto-occipitally through an intact cranium. Unwounded cats showed no significant changes in any physiological variable measured during a 100 min experimentation period. Four wounded cats survived a 90 min post-BMW period and had only a transient brainstem effect including a 50% increase in MABP concurrently with 50% reductions in the f and HR. Nonsurvivors (11 of 15) lived from 1 to 41 min after wounding. These cats initially demonstrated similar changes in MABP, f, and HR to survivors, but these variables remained unstable, possibly indicating a persisting brainstem damage. Apnea accounted for death in 10 of 11 nonsurvivors. Although the primary brainstem effect might have existed in all nonsurvivors, it appears that only one cat died from reduced respiration alone. Others had one or several postwounding secondary complications: abruptly increased ICP producing a negative CPP, extreme reductions in CO or CBF and ventilation. Cardiac arrest occurred once. Thus, post-BMW mortality cannot be consistently ascribed to the impairment of a single physiological variable. PMID- 1588607 TI - Antioxidant effects in brain and spinal cord injury. AB - Oxygen radical-mediated lipid peroxidation appears to be a critical factor in posttraumatic neuronal degeneration. Thus, numerous studies have evaluated the neuroprotective efficacy of pharmacologic agents with lipid antioxidant activity in models of spinal cord and brain injury. Intensive pretreatment of animals with the endogenous lipid peroxyl radical scavenger alpha tocopherol (i.e., vitamin E) has been shown to decrease posttraumatic spinal cord ischemia and to enhance chronic neurologic recovery. However, the slow CNS tissue uptake of vitamin E requires chronic dosing, making it an impractical agent for the treatment of acute neural injury. The glucocorticoid steroid methylprednisolone has been shown to possess significant antioxidant efficacy and, when administered to animals or humans in antioxidant dosages, improves chronic neurologic recovery after spinal cord injury. This activity of methylprednisolone is independent of the steroid's glucocorticoid receptor-mediated actions. Novel antioxidant 21-aminosteroids have been developed that are devoid of glucocorticoid activity but have greater antioxidant efficacy than methylprednisolone. One of these, U74006F or tirilazed mesylate, has been shown to be effective in animal models of brain and spinal cord injury and is currently undergoing phase II clinical trials. Compounds that combine the amino functionality of the 21-aminosteroids with the peroxyl radical scavenging chromanol portion of vitamin E (i.e., 2-methylaminochromans) have also recently shown promise as neuroprotective agents. The consistent benefit afforded by antioxidant compounds adds further support to the concept that lipid peroxidation is an important therapeutic target for acute pharmacologic neuroprotection. PMID- 1588608 TI - Axonal response to traumatic brain injury: reactive axonal change, deafferentation, and neuroplasticity. AB - Axonal injury appears to be a feature common to all traumatic brain injuries, and has been linked to much of the morbidity seen in head-injured patients. We consider how such axonal injury contributes to morbidity and also sets the stage for CNS reorganization postinjury. Efforts should continue to determine the correlates of such reorganization and to find therapeutic strategies to expedite it. PMID- 1588609 TI - Pharmacologic strategies in the treatment of experimental brain injury. AB - Although the mechanisms underlying secondary or delayed damage after traumatic injury to the central nervous system (CNS) are poorly understood, delayed neuronal injury may result from pathologic changes in the brain's endogenous neurochemistry. These neurochemical changes may include the overactivation of neurotransmitter release systems, changes in presynaptic or postsynaptic receptor binding, or the pathologic release or synthesis of autodestructive injury factors. Identification of such factors and the timing of the neurochemical cascade after CNS injury provides a window of opportunity for treatment with pharmacologic agents that modify synthesis, release, receptor binding, or physiologic activity with subsequent limitation of damage and disability. Over the past decade, a number of experimental studies have reported that modification of postinjury events by pharmacologic manipulation can promote functional recovery in a variety of animal models of CNS injury. This article summarizes the recent work suggesting that endogenous opioid peptides, catecholamines, and magnesium all play a role in the pathophysiologic cascade after brain injury and that pharmacologic manipulation of these endogenous systems may improve functional outcome after brain injury. PMID- 1588610 TI - Pharmacologic strategies in the treatment of experimental spinal cord injury. AB - Remarkable advances have been made in pharmacologic treatments of acute and chronic spinal cord injury. The recent National Acute Spinal Cord Injury Study (NASCIS) showed that very high dose methylprednisolone given within 8 hr after injury improves neurologic recovery. The mechanism is believed to be inhibition of lipid peroxidation. Many other drugs have been claimed to be beneficial in animal studies, including other lipid peroxidation inhibitors, free radical scavengers, opiate receptor blockers, NMDA receptor blockers, calcium channel blockers, inhibitors of arachidonic acid metabolism, and protease inhibitors. In chronic spinal cord injury, much progress also has been made. Myelin was found to possess factors that inhibit axonal regeneration. Blocking these factors enhances spinal cord regeneration. Monosialic gangliosides (GM1) were recently found to improve neurologic recovery in spinal-cord-injured patients. Given as late as 48 72 hr after injury, the mechanism of action is not well understood. However, the GM1 results give hope that recovery mechanisms can be manipulated pharmacologically. Nonregenerative therapy for chronic spinal cord injury is also being developed. Several drugs, including 4-aminopyridine and baclofen, respectively blockers of potassium channels and GABA-B receptors, improve conduction in demyelinated axons. These drugs may be useful for identifying patients who might benefit from remyelination therapy. Finally, NASCIS has complicated acute spinal cord injury studies. To bring a drug to clinical trial, an investigator must now determine the optimal treatment dose, timing, and duration over a range of injury severities, in comparison and combination with methylprednisolone. This requirement has so increased the scale of drug testing that multicenter laboratory trials may be necessary. PMID- 1588611 TI - Regeneration of lesioned CNS axons by neutralization of neurite growth inhibitors: a short review. AB - After trauma to the nervous system, the peripheral nervous system and the central nervous system (CNS) behave differently from each other. In the peripheral nervous system, regenerative sprouts often elongate and grow over long distances to reestablish functional connections. In the CNS, regenerative sprouts do not elongate beyond 1 mm. Tissue culture and biochemical experiments have demonstrated the presence of inhibitors of neurite growth, proteins with molecular weights 35 and 250 kDa (NI-35, NI-250) which exclusively occur in CNS myelin. Their neutralization leads to long-distance fiber regeneration in spinal cord and brain of the rat. PMID- 1588612 TI - Neural tissue transplantation and CNS trauma: anatomical and functional repair of the injured spinal cord. AB - Neural tissue transplantation has become recognized widely as a powerful experimental tool for studying structure-function relationships, development, plasticity, and capacities for regeneration in the adult CNS. In addition, this area of investigation has generated considerable interest in approaches that might be applicable to a variety of catastrophic neurological disorders. In this regard, attention has been given to neural tissue grafting as a potential therapeutic strategy in various forms of neurodegenerative disease. More recently, however, other investigations have begun to focus on the possible application of peripheral and central neural tissue transplants for promoting repair in forms of CNS trauma. This review highlights various neural transplantation approaches that have been explored primarily in the context of injury to the adult CNS, with emphasis on spinal cord injury. An overview is presented of the evolution of this area of research in terms of emerging biological perspectives, technological advances, and experimental modelling. Discussion centers on progress that has been made and a variety of theoretical and practical issues that remain to be resolved. PMID- 1588613 TI - Computed tomographic and magnetic resonance imaging classification of head injury. AB - Neuroimaging with CT and MRI is a basis for decision making in individual head injured patients and also provides a classification of patients according to severity of damage, patterns of injury, pathophysiologic mechanisms and prognosis. Such classifications can be based on the intracranial lesions identified: subdural, extradural, and intracerebral hematomas, contusions, and shearing lesions, or indirect indications of raised intracranial pressure and brain swelling: shift, obliteration of the third ventricle and basal cisterns, and signs of ischemia. The appropriate classification for early diagnosis and acute decision making may differ from the assessment of severity of damage, prognosis and late sequelae. Parallel systems of classification, suitable for these purposes, are proposed. PMID- 1588614 TI - Moderate head injury: an overview. AB - This review summarizes currently available epidemiologic, clinical, pathologic, and outcome data in patients with moderate head injury (MHI, GCS 9-12). This important subset comprises about 20% of head injuries in the United States. Affected patients usually are young, and most injuries are due to vehicular accidents. Current evidence (mortality rate and outcome) from various studies suggests an apparent dichotomy within the MHI category (9-10 vs 11-12). The former is more in keeping with the favorable subgroup of severe head injuries, and the latter is more appropriate to the mild head injury group. Should there be a reclassification based on this dichotomy? This is obviously important for clinical management and prognostication in these patients. The experimental evidence for a pathologic and biochemical substrate of MHI is reviewed. It is becoming increasing evident that biochemical mediators of secondary neuronal injury in MHI are at least as important as those attributed to severe head injury, but MHI may be more amenable to therapy. It may be prudent, therefore, to direct further effort to this subgroup of patients. Although additional study is required, the pattern of recovery in MHI as determined by extant neurobehavioral studies is analyzed. PMID- 1588615 TI - Traumatic contusions and intracerebral hematomas. AB - The authors review acute and delayed traumatic intracerebral hemorrhages. Based on recent experimental and clinical data, these injuries' clinical presentation, pathologic characteristics, and treatment are discussed. A description of traumatic hemorrhage based on biomechanics is emphasized. PMID- 1588616 TI - Bradykinin and neuronal injury. AB - Bradykinin, a nine-amino-acid peptide formed from a large precursor polypeptide (kininogen) by the action of the enzyme kallikrein (kininogenase), is the initial mediator of inflammation, and, in particular, bradykinin induces pain and alters vascular permeability. Bradykinin is one of the first compounds produced at the site of tissue injury and subsequently initiates a cascade of reactions that produce the cardinal features of inflammation. We will explore the role that bradykinin plays in various types of neuronal injury. In particular, we will focus on the role that bradykinin and other kinins play in brain and spinal cord trauma, in the pathophysiology of subarachnoid and intraparenchymal hemorrhage and ischemia, and in the initiation of nociceptive pain. This role suggests that bradykinin antagonists may be clinically useful in the therapeutic management of neurosurgical patients. PMID- 1588617 TI - Classification of civilian craniocerebral gunshot wounds: a multivariate analysis predictive of mortality. AB - Management of cerebral gunshot injuries has changed considerably since Cushing's (1916) and Matson's (1948) classification schemes, developed during World War I and World War II, respectively. These military injuries are characterized by either very high mass, low-velocity shrapnel wounds or by high muzzle velocity missiles causing extensive destruction of tissue. The preponderance of low muzzle velocity weapons seen in clinical practice and the availability of computed tomographic (CT) evaluation within minutes after presentation has altered the range of prognostic indicators available to the neurosurgeon and the amount of relative importance placed on each factor. Raimondi and Samuelson (1970) noted this difference in wound ballistics and offered a classification scheme based on initial neurologic assessment. No well-defined classification system for civilian craniocerebral gunshot wounds has been proposed that evaluates and integrates clinical, laboratory, and neuroradiologic data. A retrospective study was performed on all 62 civilians with gunshot wounds to the head admitted to the University of Virginia Hospital between December, 1984, and November, 1990. The patient population consists of 86% males and 14% females, with an age range of 10 72 years; 60% self-inflicted wounds and 32% patients who died en route or immediately upon arrival at the hospital. The overall mortality rate was 55% at 1 week postinjury. Although we have demonstrated an association between some previously defined factors and prognosis in civilian injury, such as admission Glasgow Coma Scale (GCS) (p = 0.001) and initial pupillary response (p less than 0.001), we have also defined other significant predictors of outcome including abnormal coagulation states on admission (p less than 0.001) and the neuroradiologic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588618 TI - The diagnosis of head injury requires a classification based on computed axial tomography. AB - The introduction of structural imaging of the brain by computed tomography (CT) scans and magnetic resonance imaging (MRI) has further refined classification of head injury for prognostic, diagnosis, and treatment purposes. We describe a new classification scheme to be used both as a research and a clinical tool in association with other predictors of neurologic status. PMID- 1588619 TI - Neurophysiological assessment of spinal cord and head injury. AB - Selected neurophysiologic studies can supplement clinical examination in assessing residual motor function after spinal cord or head injury. The ability of polyelectromyographic recording to detect subclinical suprasegmental control is illustrated in paraplegic patients after spinal cord injury. Excitatory or inhibitory modulation of segmental motor activity in a subpopulation of patients with clinically complete motor paralysis suggests residual connection across the lesion. This observation is consistent with the pathologic finding that complete transection of the spinal cord is rare after spinal cord injury. A preliminary study of motor-evoked potentials also indicates their potential value as an objective measure of the functional status of descending pathways. Neurophysiological assessment of subclinical residual motor function may be useful in understanding the role of suprasegmental input in the manifestation of spasticity, in objectively documenting recovery of function after injury, and may aid in the development of more specific restorative measures. Our limited experience in head-injured patients also suggests the potential usefulness of these tools in supplementing clinical evaluation. PMID- 1588620 TI - Functional assessment measures in CNS trauma. AB - How effectively the survivor of CNS trauma can function in society is the ultimate clinical outcome. Many victims of spinal cord injury (SCI) and traumatic brain injury (TBI) are frequently left with permanent impairment. Measurements of impairment, and the direct relationship to the functional loss and resultant disability, should be the gold standard for determining the effectiveness of interventions. The primary impairments in SCI are motor and sensory loss while those in TBI are neurobehavioral disorders. Classifications for impairment are reasonably well defined in SCI and several approaches are gaining wide acceptance. We hope that internationally agreed upon standards will be forthcoming within the year. The functional independence measure (FIM), which was developed in the past 6-7 years, will be added to the standards. It shows good reliability for SCI as an overall assessment and some of the specific categories of self-care and mobility. An extension of the FIM is needed for more precise measurement of function in quadriplegic subjects. Classification of impairment in TBI has been more difficult. While the Glasgow Outcome Scale has gained international acceptance for almost 10 years, it has limitations in gradations from the moderate disability to the good recovery groups. The Disability Rating Scale (DRS) has shown good reliability, better precision than the Glasgow Outcome Scale, and greater reliability than other measures. An extension of the FIM, called the functional assessment measure (FAM), and the DRS are currently being tested by regional TBI centers in the United States. Functional assessment measures should be available within the next several years. PMID- 1588621 TI - National Head and Spinal Cord Injury Prevention Program of the American Association of Neurological Surgeons and the Congress of Neurological Surgeons. AB - Organized neurosurgery has developed and promoted a national educational program for adolescents to reduce the number of head and spinal cord injuries sustained by this group of young people. The program has been adopted widely, with over 1,000,000 teenagers exposed to it since its inception in 1986. Preliminary data suggest that the program has had a favorable impact on the knowledge and attitudes of young people regarding head and spinal cord injuries, risk-taking behavior, and incidence of injuries. PMID- 1588622 TI - Prevention of brain trauma by legislation, regulation, and improved technology: a focus on motor vehicles. AB - More than half of all brain trauma is caused by motor vehicle crashes. Prevention strategies that reduce the likelihood of motor vehicle crashes or injuries to occupants will also prevent trauma. Many effective strategies have yet to be applied on a large scale. Roadway design improvements such as removal of fixed objects from roadsides, widening roadside recovery zones, installing dividers between opposing lanes of traffic, and replacing fixed utility poles with breakaway designs, have been effective in reducing crashes and injuries. Driver measures of documented benefit include the 55 mph speed limit, safety belt use laws, 21 year legal drinking age, administrative license suspension for drinking drivers, and driving curfews and postponement of licensure for teenagers. Motor vehicle safety has improved greatly since the National Highway Traffic Safety Administration began regulating vehicle design. Significant design requirements include lap and shoulder belts in front seat positions, and, more recently, automatic safety belts or air bags in front seat positions, head restraints in front seat positions, reinforcing side and roof beams, and the center-mounted brake light. The most significant future advance will be the provision of full front seat air bags in all passenger vehicles. As much as one-quarter of brain trauma can be prevented or reduced in severity by this measure alone. Further safety requirements should include head restraints in rear positions, a-pillar, b pillar, and roof padding, antilock brakes, and a vehicle rollover standard. PMID- 1588623 TI - Control of intracranial pressure in patients with severe head injury. AB - Raised intracranial pressure (ICP) occurs at some time in 50-75% of severely head injured patients. Measurement of ICP alone is not sufficient. Arterial pressure must also be monitored: the important physiological variable is cerebral perfusion pressure. Detailed analysis of the ICP recording yields valuable information on the nature and cause of ICP, with implications for appropriate therapy. Additional measurements of importance include brain electrical activity, arterial and jugular venous oxygen saturation, and blood flow velocity in major intracranial arteries measured by transcranial Doppler sonography. These assessments not only add information about the cause of intracranial hypertension (vascular vs. nonvascular) but also help to regulate therapy, providing early warning that a treatment for reducing the ICP is actually producing global brain ischemia. In the management of raised ICP, all correctable factors must first of all be dealt with, then a choice made between hypnotic drugs and osmotic therapy according to whether the cause of raised ICP is, respectively, vascular or nonvascular. PMID- 1588624 TI - Increased intracranial pressure in head injury and influence of blood volume. AB - This article reviews the progress made by the Traumatic Coma Data (TCD) bank participants in studying the influence of raised intracranial pressure (ICP) on outcome in head-injured patients and summarizes new concepts of the pathophysiologic mechanisms involved n ICP rise. PMID- 1588625 TI - Cerebral blood flow, cerebral blood volume, and cerebrovascular reactivity after severe head injury. AB - Traumatic brain injury (TBI) often causes disturbances of the cerebrovascular circulation, which contribute to the infliction of secondary injury, although the complex nature of the mechanisms involved is not fully understood. First, the role of ischemia in TBI is still controversial. Despite experimental and pathologic data suggesting important interactions between ischemia and trauma, evidence for posttraumatic ischemia with CBF measurements in patients so far had eluded most investigators. Recent data, however, indicate that low CBF and ischemia probably only occur within the first few hours after injury, yet have important impact on neurologic status and outcome. Similarly, the clinical significance of posttraumatic hyperemia is unclear. A relationship between raised intracranial pressure (ICP) and hyperemia has been suspected, but reports have not been consistent, possibly due to a dissociation between CBF and CBV in head injured patients. Measurements of CBV in the acute stage of severe head injury now have confirmed this concept, and also suggest that increased CBV may contribute to brain stiffness and elevated ICP. Impairment of cerebrovascular CO2 reactivity and autoregulation often occurs after TBI. Although no correlation with the severity of injury or outcome has been established, it is obvious that diminished adaptive responses of the cerebral vasculature render the brain more vulnerable to additional systemic insults, such as derangements of blood pressure, altered rheology, or hypoxia. The posttraumatic status of vascular reactivity and autoregulation also has important implications with regard to the treatment of high ICP, in particular for the use of hyperventilation and pharmacologic management of blood pressure, which are discussed in detail. PMID- 1588626 TI - Cerebral blood flow, AVDO2, and neurologic outcome in head-injured patients. AB - A reduced cerebral blood flow (CBF) and a widened arteriovenous oxygen difference (AVDO2) almost always have been associated with a poor neurologic outcome. The literature on this relationship is reviewed. A logistic regression analysis model of the effect of CBF on neurologic outcome was developed, which was adjusted for various confounding factors. CBF remained significantly associated with neurologic outcome-despite these adjustments. PMID- 1588627 TI - Neurobehavioral recovery. AB - This review discusses recent programs in early and late neurobehavioral recovery from closed head injury (CHI). The research on early recovery has encompassed the relationship of localized brain lesions to the duration of impaired consciousness and features of posttraumatic amnesia. Of the research on late neurobehavioral outcome of CHI, studies emanating from the Traumatic Coma Data Bank are reviewed in detail, including analysis of acute neurologic indices in relation to recovery of memory, information processing speed, and other cognitive measures. Recent studies concerning the neurobehavioral outcome of CHI in children are discussed as are investigations of behavioral disturbance, psychosocial outcome, and family variables. The review concludes with an assessment of recent studies concerning the efficacy of rehabilitation directed toward the cognitive sequelae of CHI and preliminary trials to evaluate the potential use of psychoactive drugs in the postacute management of head injured patients. PMID- 1588628 TI - Nutrition and brain injury. AB - The patient with head injury must overcome central and systemic insults. In addition to the head injury itself, the patient suffers a systemic metabolic response to injury. Both of these insults can affect the patient's ability to survive and recover. During the past decade, investigators have described the systemic metabolic result identified by hypermetabolism, hypercatabolism, the acute-phase response, decreased immunocompetence, hyperglycemia, increased counterregulatory hormone levels, increased ventricular fluid and serum cytokine levels, and altered gastric function. During the next decade, investigators will attempt to modulate this response by manipulating the types of nutrients administered, use of pharmacologic and physiological agents, and administration of growth factors. PMID- 1588629 TI - Management of cervical spinal cord trauma. AB - Trauma victims with cervical spinal cord injuries should be managed by proper immobilization and immediate reduction of spinal cord fractures to anatomical alignment. Patients must be stabilized medically, and a thorough neurologic and radiographic evaluation must precede any surgical intervention. Treatment must be individualized and depends on the level and severity of injury. New pharmacotherapies under intensive investigation offer some hope of recovery of function to patients with spinal cord injuries. Recent clinical trials with methylprednisolone indicate that the sensory and motor outcome of patients subject to trauma with spinal cord injuries improved when they received high doses within 8 hr of injury. Clinical trials are being proposed with tirilizad, a member of a new family of drugs, the 21-aminosteroids. This agent, which may be even more effective than methylprednisolone, has none of the side effects associated with other steroids. PMID- 1588630 TI - The Second National Acute Spinal Cord Injury Study. AB - In 1990, the Second National Acute Spinal Cord Injury Study reported that high dosage methylprednisolone improves neurologic recovery in spinal-injured humans. The study showed that patients who received the drug within 8 hr after injury improved, whereas those who received the drug later did not. The drug significantly increased recovery even in severely injured patients who were admitted with no motor or sensory function below the lesion, contradicting a long held dogma that such patients would not recover. Some researchers, however, have questioned the stratification of the patient population, the use of summed neurologic change scores, and the absence of functional assessments. The stratification by injury severity and treatment time was planned a priori and based on objective criteria. Detailed analyses revealed no differences between groups attributable to stratification or randomization. While multivariate analyses of the summed neurologic scores were used, the conclusions were corroborated by other analytical approaches that did not rely on summed scores. For example, treatment with methylprednisolone more than doubled the probability that patients would convert from quadriplegia or paraplegia to quadriparesis or paraparesis, analgesia to hypalgesia, and anesthesia to hypesthesia. The treatment also significantly improved neurologic scores in lumbosacral segments, indicating that beneficial effects were not limited to segments close to the lesion site. The treatment did not significantly affect mortality or morbidity. The study strongly suggests that methylprednisolone has significant beneficial effects in human spinal cord injury, that these effects occur only when the drug is given within 8 hr, and that it helps even in patients with severe spinal cord injuries. These conclusions have important implications for spinal cord injury care and research. PMID- 1588631 TI - GM-1 ganglioside in human spinal cord injury. AB - Spinal cord injury is typically a devastating injury with no or only limited neurologic recovery. Recent papers have reported enhancement of neurologic recovery following spinal cord injury with both methylprednisolone and GM-1 ganglioside. This paper provides additional details of the GM-1 study and a further analysis of recovery of motor function for each of the ten neurologic levels assessed in the study. This additional analysis provides further evidence that the largest enhanced recovery of motor function in the GM-1 treatment group occurred in the muscles of the lower extremities and is consistent with the enhanced recovery occurring in the white matter tracts passing through the level of injury. PMID- 1588632 TI - Secondary injury and acidosis. AB - Following traumatic brain injury, cells that are not directly, and thereby irreversibly damaged are subjected to ionic fluxes including potassium and calcium. This injury-induced ionic flux is a result of both neuronal firing via direct mechanical stimulation of the neurons as well as the activation of ligand gated ion channels primarily associated with excitatory amino acids (e.g. glutamate). This ionic destabilization places enormous energy demands on these cells in order to activate pumping mechanisms to reinstate normal ionic balance. The primary fuel used to acquire this energy is glucose, which results in a period of hyperglycolysis leading to the accumulation of lactate. This acute period of increased glucose metabolism lasts only during the acute period, after which these same cells exhibit a state of chronic metabolic depression for both glucose and oxygen. This metabolic derangement may prevent the necessary energy production for maintaining cellular protein synthesis which is inhibited following traumatic brain injury. This injury-induced metabolic derangement is not uniform throughout all regions. Some structures are more or less affected presumably due to their proximity to the site of trauma and/or to the extent to which they have a preponderance to being more vulnerable to insult. Within these affected regions, the metabolic dysfunction indicates that cells are functionally compromised in their ability to respond to both normal physiologic and pathophysiologic challenges. This results in the expression of neurological deficits and an enhanced vulnerability of these cells to a second insult, both of which dissipate as normal metabolic function returns over time. PMID- 1588633 TI - Astrocytic edema in CNS trauma. AB - The occurrence of astrocytic swelling in response to CNS trauma is reviewed. This response occurs rapidly and appears earlier than the reactive astrocytic response to neuronal and axonal injury. Astrocytic swelling is viewed as an exaggerated pathologic extension of normal astrocytic functions, such as regulation of extracellular ion levels and brain pH. Potential deleterious consequences of swelling, such as failure of ion homeostasis mechanisms, impaired uptake of neurotransmitters, and release of excitotoxic amino acids, are discussed. Possible pharmacologic interventions are reviewed showing that inhibition of such swelling or prevention of some of its potential deleterious consequences by an anion transport inhibitor, L-644,711, may have beneficial effects in head trauma. PMID- 1588634 TI - Macrophages and inflammatory damage in spinal cord injury. AB - Disruption of myelinated nerve fibers usually constitutes the most significant damage contributing to chronic neurologic deficits in severe spinal cord injuries. Inflammatory responses form one facet of a wide array of pathologic phenomena that combined to produce this damage. The therapeutic importance of inflammation is amplified by its delayed time-course and the number of different approaches that may be taken to its modulation. The response to trauma involves two significant waves of cellular infiltration: the first, dominated by polymorphonuclear leukocytes, peaks within a few hours; the second, by macrophages, begins after 1-2 days and reaches a peak at 5-7 days. Secondary demyelination of surviving nerve fibers and delayed loss of axons coincide with the macrophage response, and may be an example of "bystander damage" caused by the cytotoxic products of activated phagocytes. We know relatively few details of this delayed pathologic change, even in animal models. In particular, it is difficult to separate potential beneficial effects of macrophages in removing cellular debris, stimulating tissue revascularization and repair of the central nervous system environment, from the potential destructive effects associated with their phagocytic activity and their stimulation of scar formation through the release of factors that induce proliferation of peripheral cellular components within the injured spinal cord. PMID- 1588635 TI - Role of calcium in central nervous system injuries. AB - Calcium ions initiate and regulate responses of central nervous tissues to injury. Calcium ions entering injured cells will activate phospholipases, disrupt mitochondrial electron transport, and release free radicals. Neurons normally possess a large reservoir of substances to bind calcium, as well as calcium activated proteins that protect phospholipids and free radical scavengers. However, calcium entry can initiate a stereotyped injury response. Injured cells release potassium and neurotransmitters that depolarize neighboring cells and cause further calcium entry. Free radical and phospholipase attack of membranes cause lipid peroxidation, generating more free radicals and releasing arachidonic acid. Cyclo-oxygenase and lipo-oxygenase convert arachidonic acid to prostaglandins and leukotrienes, eicosanoids that cause edema and vasoconstriction. Why have neurons, the longest-lived and most important cells of the body, evolved these elaborate autodestructive mechanisms? The calcium activated injury response may serve a protective purpose. Potassium and neurotransmitter release spreads the calcium load over many cells. Membrane breakdown floods extracellular fluids with phosphates and phosphatides that bind calcium ions. Lowering extracellular calcium activity efficiently reduces the driving force for calcium entry into surviving cells. Edema and vasoconstriction resulting from eicosanoids slow calcium diffusion from blood and surrounding tissues, reducing the probability of "calcium paradox" when calcium returns. The tissue rapidly eliminates moribund cells that would otherwise consume precious metabolic resources. The possibility that the injury response may be protective has important therapeutic implications. PMID- 1588636 TI - Role of adult oligodendrocytes in remyelination after neural injury. AB - Traumatic neural injury is often accompanied by demyelination. The factors that determine the ability of the CNS to remyelinate are examined as well as the origin of the cells responsible for the remyelination. Evidence is presented that suggests that both a precursor-type oligodendrocyte as well as an oligodendrocyte that previously formed a myelin sheath are able to remyelinate in the CNS. A key determinate of the success of remyelination is the ability for either cell type to proliferate before remyelination. We have developed a method to isolate the oligodendrocyte from the mature CNS and studied the mitotic potential of these adult oligodendrocytes in vitro. In contrast to neonatal oligodendrocytes, the adult oligodendrocytes respond weakly to soluble and particulate mitogens. However, when cocultured with neurites, the adult oligodendrocytes demonstrate a more vigorous mitotic response, which may be related to the ability of the neurite to upregulate receptors which transduce the mitotic signal. Since we have identified fibroblast growth factor as a mitogen associated with the axonal plasma membrane that stimulates neonatal oligodendrocytes to divide, we have examined the redistribution of membrane-associated fibroblast growth factor in an in vitro model of neuronal injury. After neuritic injury, fibroblast growth factor containing membrane vesicles were redistributed to the surface of cocultured oligodendrocytes. After invasion of macrophages to a site of neural injury, enzymes secreted by macrophages can release extracellular stores of fibroblast growth factor into the vicinity. This burst of mitotic potential may preferentially stimulate astrocyte rather than oligodendrocyte division, leading to glial scarring and a subsequent failure of remyelination. Other factors to be considered in the potential for remyelination after injury are astrocyte-derived factors that inhibit myelination and the proteins in oligodendrocytes that prevent axonal regrowth indirectly influencing remyelination potential. Thus, provided the oligodendrocyte can gain access to relevant mitogens either in the axonal plasma membrane or in a soluble form and undergo a wave of proliferation, there is good potential for remyelination after neural injury. However, if axonal regrowth is inhibited and astrocytes preferentially are stimulated to divide and form a glial scar, the prognosis for remyelination is poor. PMID- 1588637 TI - In vivo percutaneous absorption and skin decontamination of alachlor in rhesus monkey. AB - The objectives of this study were to determine the percutaneous absorption of alachlor relative to formulation dilution with water, and to determine the ability of soap and water, and of water only, to remove alachlor from skin, relative to time. Alachlor is a preemergence herbicide. The in vivo percutaneous absorption of alachlor in rhesus monkeys was 17.3 +/- 3.3, 15.3 +/- 3.9, and 21.4 +/- 14.2% for 24-h skin exposure to Lasso formulation diluted 1:20, 1:40, and 1:80, respectively. In vivo, there was no support for increased alachlor skin absorption with water dilution, as previously reported for in vitro absorption. The average in vivo absorption of 18% applied dose over 24 h (0.75%/h) was similar to the maximum in vitro rate of 0.8%/h using human skin and human plasma as receptor fluid. Dose accountability in vivo was 80.6-95.2%. [14C]Alachlor in Lasso diluted 1:20 with water was placed on rhesus monkeys at concentrations of 23 micrograms/10 microliters/cm2. Skin decontamination at 0 h with soap and water (50% Ivory liquid 1:1 v/v with water) removed 73 +/- 15.8% (n = 4) of the applied dose with the first wash; this increased to a total of 82.3 +/- 14.8% with two additional washes. Decontamination after 1 h removed 87.5 +/- 12.4% with three successive washes. After 3 h decontamination ability decreased, and after 24 h only 51.9 +/- 12.2% could be recovered with three successive washes. Using water only, at 0 h 36.6 +/- 12.3% alachlor was removed with the first wash and the total increased to 56.0 +/- 14.0% with two additional washes. At 24 h the total amount decreased to 28.7 +/- 12.2% for three successive washes. Alachlor as Lasso in field-use rate (11 micrograms/cm2) and undiluted (217 and 300 micrograms/cm2) proportions were left on rhesus monkey skin for 12 h and decontaminated with soap and water (10% Ivory liquid v/v with water). Continual successive washes (6-8 in sequence) recovered 80-90% of the skin-applied alachlor. These results suggest that simple washing with soap and water is appropriate for removing some chemicals from skin. Decontamination with only water was less effective than with soap and water. PMID- 1588638 TI - Effects of thallium on primary cultures of testicular cells. AB - The objective of this in vitro study was to examine the response of mixed cultures of Sertoli and germ cells to treatment with thallium (Tl) at the range of concentrations that, in previous studies, was shown in vivo to affect reproduction. Cultures were prepared from the testis of Sprague-Dawley rats. Cultures containing approximately 3.75 x 10(6) cells/ml were treated with Tl concentrations corresponding to 35, 7, and 1.4 micrograms Tl/g testis, estimated from protein content of cultures. Observations at 24, 48, and 72 h after treatment showed a significant release of germ cells into the culture medium that was both concentration and time dependent. Cultures treated with 35 micrograms Tl/g testis showed a threefold increase in germ-cell detachment compared with controls after only 24 h of exposure. As the treatment time increased to 48 h of exposure, even cultures exposed at the lowest Tl concentration (1.4 micrograms Tl/g testis) showed significant loss of germ cells. After 48 h, cultures exposed to 7 micrograms Tl/g testis exhibited a 2.5-fold increase in germ-cell detachment, and those exposed to 35 micrograms Tl/g testis exhibited a 10-fold increase over controls. Morphological investigations of cell cultures showed evident loss of germ cells with significant reduction in prepachytene and pachytene spermatocytes and changes in the shape of Sertoli cells. These results are in agreement with in vivo studies, in which thallium treatment at comparable exposure levels manifested its earliest toxic testicular effects in Sertoli and germ cells. They also demonstrate the usefulness of this in vitro culture technique to assess toxic testicular damage rapidly. PMID- 1588639 TI - Arteriography of the injured extremity: are we in proximity to an answer? PMID- 1588640 TI - Counterpoint. PMID- 1588641 TI - Eye injuries in lacrosse: women need their vision less than men? AB - We describe four cases of ocular trauma incurred while playing women's lacrosse without eye protection. Women's lacrosse is potentially hazardous because, unlike men's lacrosse, helmets and face masks are not required. These ocular injuries could have been prevented with the use of protective eyewear. PMID- 1588642 TI - Elucidating the vascular response to burns with a new rat model. AB - Burn injury causes acute thrombosis and occlusion of vessels in the dermis directly killed by thermal energy. A vascular response also occurs in the uninjured dermis bordering the site of injury. Diminished blood flow leads to progressive ischemia and necrosis in the dermis beneath and surrounding the burn. If blood flow is maintained or restored in this area, the tissue survives. A noninvasive technique for studying dynamic changes in blood flow in this transitional dermis in rats is presented. A rectangular brass bar 19 mm wide with 5-mm transverse notches was heated in boiling water and applied to the skin surface for 20 seconds, making a "comb" burn composed of a row of four rectangular 10 x 19-mm full-thickness burns. Between the burns were 5 x 19-mm bands of uninjured skin, called "interspaces." After burning, blood flow near the surface of both the burn sites and the interspaces was monitored with a laser Doppler perfusion monitor for 24 hours. The vascular patency of blood vessels was directly visualized by latex vascular casts made 24 hours after burn. The possible prevention of progressive ischemia by injecting systemic ibuprofen was examined in this new model. Normal skin has a surface blood flow reading of 80 +/ 16 mV, burn sites have a reading of 11 +/- 4 mV, and interspaces have a reading of 21 +/- 4 mV at 24 hours postburn in untreated rats. Systemic ibuprofen given IM immediately postburn at 12.5 mg/kg increased blood flow to 80 +/- 28 mV within the interspaces, to 17 +/- 12 mV in the burn site, and to 80 +/- 9 mV in normal skin. The vascular casts showed an absence of patent vessels within both the burn sites and interspaces in untreated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588643 TI - Intra-abdominal sepsis and adrenergic receptor response. AB - This study measured the adrenergic receptor response of 13 patients with severe intra-abdominal sepsis, who required laparotomy and an open abdominal closure with Marlex mesh. The source of the sepsis was gram-negative organisms of intestinal origin. There were seven survivors and six nonsurvivors. When the patients were stratified into survivors and nonsurvivors, the Septic Severity Score, the APACHE II score, the Acute Physiological Score, and the Glasgow Coma Scale score results were not significantly different between groups. The alpha-2 and beta-1 adrenergic receptor responses were measured in the adipose tissue of the abdominal wall and the small bowel mesentery on day 1 of admission to the intensive care unit. The results demonstrated that the alpha-2 and beta-1 receptors of the nonsurvivors had a significantly decreased receptor response with desensitization and down regulation. The alpha-2 and beta-1 receptors of the survivors had an increased response with hypersensitization and up regulation. This study indicates that the adrenergic receptor pattern is distinctly different between survivors and nonsurvivors with severe abdominal gram-negative sepsis. The pattern differences occurred early (within 24 hours) when the patients had similar physiologic profiles. It is concluded that adrenergic receptor response may be a biologic indicator of the magnitude of the septic injury and a predictor of outcome. PMID- 1588644 TI - Prevention of infection in burns: preliminary experience with selective decontamination of the digestive tract in patients with extensive injuries. AB - Evidence from studies of trauma patients suggests that selective decontamination of the digestive tract (SDD) might also be of value in preventing colonization and infection by enteric organisms in burn patients. In a retrospective study, 31 consecutive patients with burns of greater than 30% of total body surface area, admitted over a 2-year period, who were treated with an SDD regimen, were compared with a similar group of 33 consecutive patients admitted in the 2 years immediately preceding the introduction of SDD. Fewer SDD-treated patients developed wound colonization with Pseudomonas species (29% vs. 61%), or with Enterobacteriaceae (10% vs. 73%). Similar reductions in colonization with gram negative organisms were found in urine and gastric aspirates. There were fewer respiratory infections in the SDD group (6.5% vs. 27.3%), and only one patient developed septicemia, compared with eight in the control group (3.2% vs. 24.2%). Fewer SDD-treated patients died (one death, compared with seven in the non-SDD group). These results suggest that SDD may be of value in the management of patients with severe burn injuries, but further studies are required to test the validity of this conclusion. PMID- 1588645 TI - Impact of the Los Angeles County Trauma System on the survival of seriously injured patients. AB - We compared the survival of 658 seriously injured patients treated in Los Angeles County in the Fall of 1982 (prior to the activation of the trauma system) with that of 766 such patients treated in the Fall of 1984 (when the system was young and composed of essentially a full complement of trauma centers). We demonstrated a statistically significant improvement in the adjusted odds of survival for 1984 over 1982 with regard to victims of motor vehicle collisions who sustained multiple serious injuries (1980 Injury Severity Score: 26-50) (p = 0.042). For the data set as a whole, although an improvement in survivorship over this period was suggested by the data, statistical significance could not be demonstrated. PMID- 1588646 TI - Sequential fractures of both hips in elderly patients--a prospective study. AB - Thirty-five patients with sequential fractures of both hips were studied prospectively. The second hip fractures occurred more commonly if the patients were institutionalized, if they suffered from concomitant neurologic diseases such as previous stroke or Parkinsonism, or if there was biochemical evidence of osteomalacia. Twelve patients sustained the contralateral hip fracture within 12 months of the first one. There was a significant correlation between biochemical evidence of osteomalacia and early occurrence of the second hip fracture. Although rehabilitation was difficult for such patients, it was possible with a longer period of intensive physiotherapy; only three patients were not able to walk upon discharge from the hospital after the second hip fracture. PMID- 1588647 TI - Primary repair of traumatic aortic rupture: a preferred approach. AB - Eighty patients with traumatic rupture of the thoracic aorta were treated. Seven patients died during the initial resuscitation. Forty-three patients underwent surgical repair using the clamp-and-sew technique; 14 patients had a heparin bonded shunt placed, and 16 patients were repaired using cardiopulmonary bypass. An interposition Dacron graft was used in only 19 patients (26%). The last 32 consecutive patients underwent primary repair of the ruptured aorta. Overall mortality was 19.2% (14 of 80); 9 of 14 patients (64%) had laparotomies along with the aortic repair, and 13 of 14 patients (92%) had three or more associated major injuries. Paraplegia occurred in four cases (5.6%). Traumatic aortic rupture remains a difficult surgical problem. Primary repair, without graft interposition, is the preferred technique and can be accomplished even when the two aortic ends have retracted several centimeters. PMID- 1588648 TI - Oxygen consumption early postburn becomes oxygen delivery dependent with the addition of smoke inhalation injury. AB - We determined the relationship between oxygen delivery, DO2, and oxygen consumption, VO2, in sheep after a moderate smoke inhalation injury and 15% TBSA third-degree burn compared with burn alone and controls. Comparison was made beginning three hours after injury when carboxyhemoglobin levels were back to baseline values. We decreased DO2 between three and eight hours by 25% by either removing blood (controls) or decreasing the resuscitation fluid infusion rate. Lung oxidant, measured as tissue malondialdehyde (MDA) levels, and histologic changes were also assessed. Animals were killed at 24 hours. We found that in controls and animals with a burn alone, a 25% decrease in DO2 was compensated for by an increase in O2 extraction, maintaining VO2 constant. Correlation of DO2 to VO2 was r2 = 0.3, indicating independence of VO2 from DO2. With the combined injury, VO2 decreased in proportion to DO2, since O2 extraction did not increase. The correlation of DO2 to VO2 was r2 = 0.9, indicating delivery-dependent consumption, a pathologic process most likely caused by increased inflammatory mediators from the combined injury. Lung lipid peroxidation was markedly increased in the combined injury, 148 +/- 18 nmol MDA/gram of tissue compared with burn alone, 64 +/- 5 nmol/g, or controls, 45 +/- 4 nmol/g. However, no decrease in arterial O2 tension or increase in lung water was noted, i.e., the sheep did not have ARDS, which is known to impair O2 extraction. We conclude that a pathologic O2 delivery-dependent consumption develops with the combination of burn and inhalation injury, increasing the potential for tissue hypoxemia. This change corresponds with increased lung tissue oxidant change. PMID- 1588649 TI - Coagulopathy and catecholamines in severe head injury. AB - The prospective study reported here evaluated the relationship between coagulopathy, catecholamines, and outcome in severe head trauma. Thirty-six trauma patients (10 with penetrating injuries, 26 with blunt injuries, 50% overall mortality) were evaluated. These patients had severe head trauma (Glasgow Coma Scale score less than 9). Blood was analyzed for platelet count, prothrombin time (PT), partial thromboplastin time (PTT), and fibrinogen, D-dimer, antithrombin III, protein C, and protein S levels. A 24-hour urine sample was collected for vanillylmandelic acid (VMA), normetanephrine, and metanephrine determinations. A control group of five patients undergoing elective neurosurgery was also studied. Statistically significant differences between head injury survivors and nonsurvivors were present for platelet count, PT, and fibrinogen activity. There were no differences in the results of the other coagulation tests or in urinary catecholamine levels. The trauma patients differed from the elective neurosurgery patients with regard to D-dimer levels, PT, PTT, protein C levels, and urinary normetanephrine concentrations. Head trauma patients have a coagulopathy that is absent in patients following elective neurosurgical procedures. The coagulopathy may correlate with poor survival in head trauma and may be related to a catecholamine surge. PMID- 1588650 TI - Does blood transfusion or hemorrhagic shock induce immunosuppression? AB - Blood transfusions have been implicated in predisposing patients to infection by inducing immunosuppression. This study evaluated the effects of syngeneic (ST) and allogeneic (AT) blood transfusion with and without hemorrhagic shock (HS) to determine whether transfusion or the accompanying hemorrhage affected certain components of the immune response. Lewis rats received ST or AT at 10%, 20%, or 30% of blood volume. Hemorrhagic shock was induced in other animals, which were resuscitated with either shed blood or substituted 10%, 20%, or 30% ST or AT. Intradermal staphylococcal abscess size, peritoneal leukocyte elicitation, and peritoneal macrophage Ia receptor expression were selected to measure the immune system response. Hemorrhagic shock increased abscess size significantly (p less than 0.05), but ST or AT alone or in combination with HS had no effect. Both shock and transfusion per se increased macrophage Ia receptor expression (p less than 0.05), but no additive or synergistic effect was observed. Peritoneal leukocyte elicitation was not affected by HS, ST, or AT. These results suggest that HS and not blood transfusion is a major determinant of the risk of infection. PMID- 1588651 TI - Human cerebrovascular response to oxygen and carbon dioxide as determined by internal carotid artery duplex scanning. AB - Alterations in arterial oxygen and carbon dioxide influence cerebrovascular resistance and therefore cerebral blood flow (CBF), but the magnitude of these CBF responses have not been well defined in normal humans. Duplex scanning (B mode imaging and pulsed Doppler shift analysis) was used to measure internal carotid blood flow (ICBF) as an indicator of CBF in 20 normal subjects during alterations of arterial O2 and CO2. End-tidal PCO2 (PETCO2) was measured by mass spectrometry, arterial oxygen saturation by pulse oximetry, and unilateral (right) ICBF by duplex scanning. A variety of gas mixtures were administered to achieve hypoxemia (FIO2 = 0.075-0.10) and hypercapnia (FICO2 = 0.05) or the subject was asked to hyperventilate to PETCO2 = 16-24 mm Hg. The ICBF was determined five times in each of six conditions: (1) normoxia/normocapnia; (2) normoxia/hypercapnia; (3) normoxia/hypocapnia; (4) hypoxia/normocapnia; (5) hypoxia/hypercapnia; and (6) hypoxia/hypocapnia. During normoxia and normocapnia, the mean ICBF was 330 +/- 19 (SEM) mL/min. Specific CO2 reactivity was 7.4 +/- 0.7 mL/min/mmHg, which is equivalent to 2.3% +/- 0.1% of normocapnic blood flow per mm Hg change in CO2. During normocapnia, ICBF increased by 2.9 +/- 0.9 mL/min for each percentage decrease in oxygen saturation. Using an ANOVA with repeated measures to fit the responses, the following statistically significant relationship was found: ICBF (mL/min) = 333 + 6.3.(PETCO2 - 40) + 2.7 DSO2 +/- 81 where DSO2 is arterial desaturation (100 - arterial saturation). An additional "between subject" variation had a mean of 0 and a standard deviation of 82 mL/min. There was no statistically significant evidence of an interaction between O2 and CO2 response. Our data suggest that hypoxia and carbon dioxide changes will alter CBF simultaneously and additively. Duplex scanning of the internal carotid artery, which can be performed at the bedside, is sufficiently sensitive to detect changes in ICBF and internal carotid artery oxygen delivery. PMID- 1588652 TI - Continuous monitoring of cerebral hemodynamic reserve in acute brain injury: relationship to changes in brain swelling. AB - A new concept of cerebral hemodynamic and metabolic physiology, cerebral hemodynamic reserve (CHR), was evaluated in 20 comatose adults with acute traumatic brain swelling who were undergoing continuous monitoring of the arteriojugular difference in oxyhemoglobin saturation, along with cerebral perfusion pressure and expired PCO2. The CHR was measured as the ratio of relative (percent) changes in cerebral oxygen extraction to relative changes in cerebral perfusion pressure during spontaneous increases in intracranial pressure. In patients with initially severe brain swelling, the CHR was more frequently abnormal (compromised) on the first day, and tended to improve on the second day. In patients with initially moderate brain swelling, the CHR was more frequently normal (preserved) on the first day, but tended to become compromised on the second day if the brain swelling exacerbated. It is concluded that cerebral hemodynamic reserve abnormalities very closely associate with signs of increased intracranial "tightness" on computed tomographic scans of the head. Cerebral hemodynamic reserve could therefore become an important guide in the functional evaluation and management of acute brain swelling (focusing on cerebral oxygenation and perfusion pressure) in a variety of predominantly diffuse acute intracranial disorders. PMID- 1588653 TI - The impact of motorcycle helmet use. AB - Mandatory motorcycle helmet-use legislation is supported by the high morbidity of motorcycle trauma and its cost to society. Opponents argue, however, that the majority of motorcycle trauma morbidity and costs are the result of injuries to body regions other than the head. Previous data do not address this argument because they fail to control for differences in non-head injury severity (i.e., kinetic impact) between helmeted and unhelmeted patients. This study investigates the impact of helmet use on the morbidity and cost of motorcycle trauma, after controlling for non-head injuries. A retrospective review of all patients admitted to Harborview Medical Center with motorcycle trauma from 1/1/85 to 1/1/90 was performed. Non-head injury severity was determined by calculating an ISS that did not include head injury. This non-head ISS was used to control for injury severity below the neck. Four hundred twenty-five patients were identified. Stratified analysis showed that helmet use decreased the need for and duration of mechanical ventilation, the length of ICU stay, the need for rehabilitation, and prevented head injury. Costs of acute care were significantly less in helmeted patients. Regression analysis, controlling for age, gender, and blood alcohol level (as well as non-head injury severity), confirmed that acute costs were 40% less with helmet use. PMID- 1588654 TI - Trauma: the leading cause of maternal death. AB - The records of the Cook County Medical Examiner were reviewed for the period January, 1986, to December, 1989. Ninety-five maternal deaths were identified. The causes of maternal death were categorized as direct maternal, indirect maternal, or nonmaternal. Direct maternal causes of death (18.9%) were the result of complications of pregnancy, labor, delivery, or its management. Indirect maternal causes of death (12.6%) occurred when pre-existing health problems were exacerbated by pregnancy. All other maternal deaths were the result of nonmaternal causes. Nonmaternal causes of maternal death were further classified as traumatic or nontraumatic. Traumatic maternal deaths (46.3%) were attributed to homicide in 57% and suicide in 9%. The mechanism of injury in traumatic maternal deaths included gunshot wounds (22.7%), motor vehicle crashes (20.5%), stab wounds (13.6%), strangulation (13.6%), blunt head injuries (9.1%), burns (6.8%), falls (4.5%), toxic exposure (4.5%), drowning (2.3%), and iatrogenic injury (2.3%). Trauma was therefore the leading cause of maternal death, accounting for 46.3% of deaths in this series. PMID- 1588655 TI - Coagulopathy and intraoperative blood salvage (IBS). AB - The use of potentially contaminated shed blood and the contribution of autotransfused blood to coagulopathy are controversial issues associated with intraoperative blood salvage (IBS) in trauma patients. Intraoperative blood salvage was used in 154 trauma patients and resulted in reinfusion of 7.97 units per patient. Moderate to severe abnormalities of the prothrombin time (PT) and partial thromboplastin time (PTT) occurred in 39 patients (31%). Prolongation of the PT and PTT occurred with increasing transfusion. Coagulopathy was seen in patients receiving greater than 15 IBS units and in patients receiving greater than 50 combined units of blood. Of the 66 patients with bowel injury, 58 patients received shed blood. Patients with bowel injury showed no increase in infection but did develop prolongation of PT and PTT at lower levels of IBS transfusion. Based on the results of this study, patients receiving greater than 15 units of IBS transfusion require careful monitoring and factor replacement, and IBS transfusion should be limited to less than 10 units in patients with bowel injury. PMID- 1588656 TI - Lower extremity fracture fixation in head-injured patients. AB - Compared with nonsurgical management or delayed repair, early fracture fixation can reduce the incidence of pulmonary complications in patients with long-bone fractures of the lower extremities. Blunt trauma victims often have multiple nonskeletal injuries that might influence the risk of pulmonary complications, and when head injuries are present it has been a common practice to delay nonemergent operations for several days to protect the injured brain. We conducted a retrospective review of 114 patients with multiple trauma whose injuries included head trauma and a fracture of the neck or shaft of the femur or shaft of the tibia to determine if delayed stabilization of lower extremity fractures increased the risk of pulmonary complications or reduced the risk of cerebral complications. Forty-six patients underwent surgical fixation of their fractures within 24 hours of injury (early fixation), 26 patients had their fractures repaired more than 24 hours after injury (late fixation), and 42 patients did not undergo surgical fracture fixation. The risk of pulmonary complications was not related to the timing of surgical fracture fixation but was strongly influenced by the severity of injuries to the head and to the chest (p less than 0.001). Furthermore, a delay in fracture fixation did not protect the injured brain; the risk of CNS events was determined by the severity of the head injury (p less than 0.0001). Early fracture fixation in patients with head injury may be appropriate because it simplifies patient care and does not seem to worsen the head injury, but it does not prevent pulmonary complications in these high risk patients. PMID- 1588657 TI - An analysis of errors causing morbidity and mortality in a trauma system: a guide for quality improvement. AB - The purpose of auditing trauma care is to maintain quality assurance and to guide quality improvement. This study was conducted to identify the incidence, type, and setting of errors leading to morbidity and mortality in trauma patients. Determinations of the Medical Audit Committee of San Diego County were reviewed and classified by the authors for identification of preventable errors leading to morbidity or mortality. Errors were classified by type and categorized by phase of care. Errors were identified in the cases of 4% of all patients admitted for trauma care over a 4-year period. Of all trauma patient deaths, 5.9% were considered preventable or potentially preventable. The most common single error across all phases of care was failure to appropriately evaluate the abdomen. Although errors in the resuscitative and operative phases were more common, critical care errors had the greatest impact on preventable death. The detected error rate of 4% may represent the baseline error rate in a trauma system. While regionalized trauma care has dramatically reduced the incidence of preventable death after injury, efforts to further reduce preventable morbidity and mortality may be guided by an identification of common errors in a trauma system and their relationship to outcome. PMID- 1588658 TI - Computed tomography for the evaluation of knife impalement injuries: case report. AB - A patient with a stab wound to the back with suspected major vascular injury was evaluated by computed tomography instead of arteriography. The computed tomographic (CT) scan demonstrated no injury to the aorta, inferior vena cava, or esophagus, which were adjacent to the blade, and excluded a hematoma. The information from the CT scan made possible a less extensive surgical procedure than might have otherwise been necessary. PMID- 1588659 TI - Defining the major trauma patient and trauma severity. PMID- 1588660 TI - Obesity and increased mortality in blunt trauma. PMID- 1588661 TI - Diagnostic peritoneal lavage: accuracy in predicting necessary laparotomy following blunt and penetrating trauma. PMID- 1588662 TI - "Minor falls" are not fatal. PMID- 1588663 TI - Driving under the influence--a level I trauma center's experience. PMID- 1588664 TI - Transesophageal echocardiography (TEE) for initial examination of patients with blunt chest trauma. PMID- 1588665 TI - European Association of Poison Centres and Clinical Toxicologists. PMID- 1588666 TI - Predicting severity of tricyclic antidepressant overdose. AB - The measurement of plasma concentration, a prolonged QRS interval, and level of consciousness have all been recommended as useful indicators of toxicity following tricyclic antidepressant overdose. The aims of this study were firstly, to determine the relative prognostic value of each of these indicators and secondly, to assess when a patient can be discharged safely from the intensive care unit. Data were evaluated on 67 patients with tricyclic antidepressant overdose from four centers. Plasma tricyclic antidepressant concentrations were measured, coma grade was evaluated using the Matthew-Lawson Coma Scale and a ECG was obtained from 23 patients on admission. Complications such as convulsions, hypotension, arrhythmias, and need for intubation and ventilation were recorded. Thirty patients developed complications and no patient died. Coma grade was the best predictor of outcome. The development of serious complications is unlikely in patients whose level of consciousness is grade II or less and who are admitted to hospital more than 6 h after overdose. Plasma tricyclic antidepressant concentration was of no additional value in predicting toxic complications or deciding when the patient could leave the intensive care unit. Our study suggests that an alert and orientated patient with a QRS duration less than 100 ms is the best indicator for safe transfer to a medical or psychiatric ward. PMID- 1588667 TI - Severe amitriptyline overdose: relationship between toxicokinetics and toxicodynamics. AB - The clinical features and toxicokinetics of amitriptyline were studied in nine patients with severe amitriptyline poisoning. Amitriptyline and amitriptyline metabolites were studied in plasma, red blood cells, and cerebral spinal fluid. Eight patients were intubated and six required assisted ventilation. Two patients had ventricular arrhythmias, three patients convulsions and two were hypotensive. All complications developed within four hours of admission. Early in the course of the intoxication the QRS duration correlated with plasma, unbound and red blood cell nortriptyline concentration. The QRS duration also correlated with unbound but not the plasma amitriptyline concentration. The level of consciousness correlated with the plasma and unbound amitriptyline both in alpha and beta phase and with red blood cell amitriptyline in alpha phase. There was no correlation between nortriptyline concentration and level of consciousness. No correlation between coma grade or QRS duration and cerebral spinal fluid concentration of amitriptyline was found. There was no correlation between any hydroxymetabolite in blood or cerebral spinal fluid and QRS duration or coma grade. The beta half-life for amitriptyline was shorter for two patients with high concentrations of hydroxymetabolites. Although intubated, neither patient required assisted ventilation or developed complications. Because of the wide range of concentrations of amitriptyline and amitriptyline metabolites observed between individuals, it is not possible to predict outcome based on a single tricyclic antidepressant concentration. PMID- 1588668 TI - Amitriptyline and amitriptyline metabolites in blood and cerebrospinal fluid following human overdose. AB - The toxicokinetics of amitriptyline were studied in nine patients admitted to hospital in Matthew-Lawson Coma Scale grade III-IV after an estimated ingestion of 1-5 g amitriptyline. Gastric lavage was performed and 50 g activated charcoal were given orally. Venous blood samples were taken on admission and at 1, 2, 4, 8, and 24 h, and in some patients at 36 and 48 h after admission. Arterial blood samples were taken at 1, 4, 8, and 24 h after admission. Lumbar punctures were performed 1 h after admission in 8 patients and again 4 h later in 5 patients. A urine sample was screened for other drugs. The bound and unbound fraction of amitriptyline and its metabolites nortriptyline, E and Z forms of 10-OH amitriptyline and nortriptyline were analyzed in plasma, whole blood, red blood cells, and cerebrospinal fluid using an HPLC technique. The T1/2 alpha and T1/2 beta for amitriptyline were 1.5 - 3.1 and 15 - 43 h respectively. The rate of elimination of amitriptyline was not dose-dependent. The arteriovenous differences in the total amitriptyline+nortriptyline concentration were maximal in patients admitted soon after intake of drugs. Amitriptyline concentrations in cerebrospinal fluid were quantitatively similar to the unbound amitriptyline concentration in blood. The highest cerebrospinal fluid amitriptyline concentration was 506 nmol/L. There were large individual differences in plasma, blood and cerebrospinal fluid concentrations between different individuals. Repeated quantitative analysis of amitriptyline and its metabolites is unlikely to contribute to the clinical management of most patients with amitriptyline overdose. PMID- 1588669 TI - Intravenous regional calcium gluconate perfusion for hydrofluoric acid burns. AB - We report a case in which acute digital hydrofluoric acid burns were treated with regional intravenous perfusion of calcium gluconate to relieve pain and protect from further tissue damage. This is the first documented instance of this technique being used. The conventional treatments for digital hydrofluoric acid burns all have their shortcomings; intravenous regional perfusion of calcium gluconate may be an effective method of treatment for digital hydrofluoric acid burns. PMID- 1588670 TI - Cerebral edema following acute sodium valproate overdose. AB - We report a case of cerebral edema resulting from acute sodium valproate poisoning. This was associated with abnormalities of liver and renal function, hypocalcaemia and generalized muscle spasms. PMID- 1588671 TI - In vitro binding characteristics for cesium of two qualities of prussian blue, activated charcoal and Resonium-A. AB - The in vitro binding characteristics of radioactive 137Cs to two forms of Prussian blue [colloidally (soluble) K3Fe[Fe(CN)6] and insoluble Fe4[Fe(CN)6]3] and to activated charcoal and sodium polystyrene sulfonate (Resonium-A) were investigated by constructing Langmuir isotherms at pH = 1.0, 6.5 and 7.5 at 37 degrees C. At the three pHs investigated, 137Cs binding to activated charcoal and sodium polystyrene sulfonate was negligible. Binding of 137Cs to insoluble Prussian blue exceeded that for the soluble form and was pH dependent for both formulations. Maximum binding capacities were 87 mg/g (pH = 1.0), 194 mg/g (pH = 6.5) and 238 mg/g (pH = 7.5) for the insoluble form and 48 (pH = 1.0), 73 (pH = 6.5) and 78 (pH = 7.5) for the soluble form. As activated charcoal did not bind 137Cs, charcoal hemoperfusion is of no value. This has been confirmed by an in vitro experiment, using a Gambro Adsorbs 300 C cartridge. PMID- 1588672 TI - Induction of DNA-repair synthesis (UDS) in rat pleural mesothelial cells by urine of subjects exposed to genotoxic agents. AB - Unscheduled DNA synthesis was determined in confluent rat pleural mesothelial cells arrested in G0/G1 with hydroxyurea by the measurement of [3H]thymidine incorporation into DNA. Cells were treated with concentrated urine or serum from subjects exposed to certain genotoxic agents, i.e. eight cancer patients treated with radiotherapy and/or chemotherapy (r/c cancer patients) and six chromium workers. Two additional groups consisted of six nonoccupationally exposed healthy smokers and five control volunteers who were nonsmokers and nonexposed. [3H]thymidine incorporated into DNA of all samples was measured by liquid scintillation counting and of urine samples from r/c cancer patients by autoradiography. Compared to the level observed in untreated cells, a statistically significant increased [3H]thymidine incorporation was found in cells treated with urine from 7 of 8 r/c cancer patients and from 5 of 6 chromium workers. In contrast, urine from control volunteers had no effect on the unscheduled DNA synthesis response and urine from only one smoker significantly enhanced [3H]thymidine incorporation into DNA. No clear-cut difference between groups was obtained with serum. These results suggest that urine could be useful to monitor subjects exposed to genotoxic agents. PMID- 1588673 TI - INTOX: a computerized trilingual poisons information package. PMID- 1588674 TI - The cardiovascular system after scorpion envenomation. A review. AB - Scorpion envenomation is a common medical problem and life hazard in many countries of the world. Scientific investigations have addressed the interrelationship between the stimulatory effects of the venom on the autonomic nervous system and adrenals and the subsequent effects of released transmitters on the cardiovascular system. A number of clinical cardiovascular syndromes may dominate the initial clinical presentation after envenomation: the syndromes usually vary with the age of the victim, the size of the offender and the season. Central nervous system dysfunction is seen in children but rarely observed in adults; if accompanied by severe hypertension the clinical picture is consistent with acute hypertensive encephalopathy. Heart failure, pulmonary edema or a shock like syndrome has been observed in 25% and hypertension in 30% to 77% of our patients. The electrocardiographic abnormalities recorded in the majority of the patients after envenomation include an "acute myocardial infarction-like pattern." Rhythm disturbances are frequent but conduction abnormalities are rare. Echocardiographic, radionuclide and experimental hemodynamic observations have provided evidence that heart failure and pulmonary edema after envenomation are multifactorial with diminished systolic performance following the initially increased left ventricular contractility and decreased ventricular diastolic compliance. Clinical laboratory data reporting increased catecholamine metabolite excretion and elevated plasma renin and aldosterone are consistent with the stimulatory effects of the venom on the autonomic nervous system. Treatment, including our experience with vasodilators and calcium channel blockers, is reviewed. PMID- 1588675 TI - Influence of assay methods on serum concentrations of digoxin during FAB fragment treatment. AB - The treatment of digoxin intoxication has been revolutionized by digoxin specific antibody fragments (Fab). Serum digoxin concentrations may be inaccurate after this treatment. We report a case of digoxin intoxication where the results of serum concentration determinations were strikingly disparate depending on the assay used. To investigate this discrepancy we compared serum samples spiked with digoxin from 0-50 ng/mL in the presence of increasing concentrations of digoxin specific Fab-fragments. Samples were measured using the Abbott TDx assay with and without ultrafiltration of the sample and the Dade-Stratus radial partition assay. The TDx assay was statistically reduced by the Fab-fragments although the magnitude of the effect was small. The radial partition assay was dramatically affected by the addition of Fab-fragments. The predicted non-Fab bound concentration correlated highly with the measured concentration. When samples were ultrafiltered prior to TDx assay, the measured concentration was dramatically depressed but the regression of predicted non-Fab bound concentration versus observed had a significantly lower slope than for the radial partition assay. We hypothesize that this difference is due to serum protein binding in addition to Fab-fragment binding. We conclude that the radial partition assay gives the best approximation of digoxin concentration remaining unbound to Fab-fragments. Ultrafiltration followed by TDx assay gives an acceptable approximation. PMID- 1588676 TI - Massive strychnine intoxication: serial blood levels in a fatal case. AB - A fatal case of strychnine intoxication is reported. The patient expired despite early aggressive management and prevention of metabolic complications. Serial blood levels are reported. In contrast to a previous report describing first order elimination kinetics, our data suggest that strychnine follows Michaelis Menton elimination kinetics. The case illustrates the rapid, dramatic course of severe strychnine ingestions. A review of the toxicokinetics, mechanism of action and treatment of strychnine intoxication follows. PMID- 1588678 TI - Poisoning of an urban family due to misapplication of household organophosphate and carbamate pesticides. AB - A case report of an urban family who experienced excessive exposure to organophosphate and carbamate pesticides is presented. All three family members developed symptoms that were compatible with cholinesterase inhibition: headache, lightheadedness, wheezing, shortness of breath, nausea, and fatigue. Serial measurement of red blood cell and serum cholinesterases soon after exposure and during subsequent months confirmed the diagnosis of pesticide poisoning. This report demonstrates that the misapplication of pesticides commonly used in residences in urban areas can cause acute pesticide poisoning and demonstrates the usefulness of repeated measurements of cholinesterase during the post exposure period in establishing the correct diagnosis. PMID- 1588677 TI - Exchange transfusion and multidose activated charcoal following vancomycin overdose. AB - The inadvertent administration of a concentrated vancomycin solution to a 47 day old premature male twin resulted in extremely high vancomycin levels and altered renal function. A 1.5 volume exchange transfusion did not change the measured vancomycin level. Multiple doses of oral activated charcoal, 1 g/kg, were administered beginning 5 h after the exchange transfusion. A calculated half-life of vancomycin before the exchange transfusion was 35 h. The half-life after the exchange transfusion and during charcoal administration was calculated to be 12 h. The only apparent adverse effect of this vancomycin overdose was reversible nephrotoxicity. The infant's hearing, tested by brainstem auditory responses, was normal. The higher volume of distribution of vancomycin in infants may preclude removing significant amounts of this drug by exchange transfusion. Gastrointestinal dialysis with activated charcoal warrants consideration in cases of vancomycin overdose in neonates. PMID- 1588679 TI - Buflomedil intoxication: the little-known risk. AB - A life-threatening intoxication, requiring ventilatory support, is reported from the ingestion of 3.05 g of buflomedil, a peripheral vasodilator. Buflomedil at a dosage of 50 mg/kg weight produces seizures. Hypotension is not a specific symptom of intoxication. Buflomedil poisoning can be easily confused with other drugs, especially tricyclic antidepressants. PMID- 1588680 TI - Verapamil overdose and severe hypocalcemia. PMID- 1588681 TI - Investigation of an experimental weight-training programme. AB - The aim of this study was to compare the effects of conventional weight-training (control) with an experimental programme. The training programme consisted of 12 sessions, 3 a week for 4 weeks. The experimental group (n = 12) performed sets of forearm flexion with a barbell until a 20% decline in maximal force was noted. The controls (n = 11) trained according to established weight-training principles. Isometric tests were performed on both the right and left forearm flexors and during forearm flexion with a barbell: the tests were continued for a 3-week post-experimental period. The subjects were matched on all tests at the start of the experiment. Larger reductions in muscle torque within the training sessions were noted among the experimental subjects--19.8 +/- 2.0, 16.9 +/- 1.9 and 18.0 +/- 1.8% for right, left and combined elbow flexion respectively, compared to 11.8 +/- 2.7, 14.9 +/- 4.1 and 13.4 +/- 3.1% for the controls. The volume of training (number of lifts) was 30.4% higher for the experimental subjects. Muscle strength increased in both groups (P less than 0.05). The controls improved by 12.7 +/- 6.9, 24.9 +/- 22.1, 18.3 +/- 12.3 and 30.3 +/- 11.1% for right, left, combined isometric strength and the barbell test respectively. These did not differ significantly from the corresponding results for the experimental group--7.6 +/- 8.8, 17.0 +/- 12.4, 11.8 +/- 9.3 and 29.1 +/- 10.6% (P greater than 0.05). Neither the decrease in force during a single training session nor the volume of training were related to the training effect expressed as an increase in muscle force (P greater than 0.05). The effectiveness of the conventional programme in producing similar improvements in muscle strength to the experimental programme suggests that a high volume of training is unnecessary for strength gains. PMID- 1588682 TI - Physiological and metabolic responses of men and women to a 5-km treadmill time trial. AB - Previous studies have reported strong correlations between 5-km performance times and maximal oxygen uptake (VO2 max) and also for running speeds equivalent to blood lactate concentrations of 4 mM. However, there is little information on the physiological responses of individuals during races over this distance. Therefore, the aim of the present study was to measure the physiological and metabolic responses of endurance trained male (n = 8) and female (n = 8) runners during a 5-km time trial using an instrumented treadmill. Performance times were 18.77 +/- 1.27 min for the men and 21.80 +/- 1.98 min for the women (P less than 0.01). The corresponding times on the athletics track were 17.68 +/- 0.39 min for the men (P less than 0.05) and 20.70 +/- 2.16 min for the women (N.S.). During the treadmill time trials, both the men and women were able to utilize approximately 90% VO2 max, 82% VE max, 98% HR max and produce similar concentrations of blood lactate. Although the physiological and metabolic responses of these endurance-trained men and women to 5-km treadmill running were similar, the faster running times recorded by the men in this study were the result of their higher VO2 max values. PMID- 1588683 TI - Physical, physiological and performance differences between Canadian national team and universiade volleyball players. AB - Volleyball has been described as an 'interval' sport with both anaerobic and aerobic components. At the higher skill levels, technical performance may be limited by physical characteristics as well as physical fitness, and performance characteristics such as speed and vertical jump. This investigation compared teams at the two uppermost levels of men's volleyball in Canada for differences in physical, physiological and performance characteristics. The subjects were members of the national (n = 15) and universiade teams (n = 24). The parameters examined included percent body fat, maximal oxygen uptake (VO2 max), anaerobic power, bench press, 20-m sprint time and vertical jumping ability. The only significant difference in physical characteristics between the two teams was in age. Despite similarities in standing and reach height, the national team players had significantly higher block (3.27 vs 3.21 m) and spike (3.43 vs 3.39 m) jumps. An evaluation of anaerobic power measures produced similar power outputs during a modified Wingate test, yet the national team members had higher scores (P less than 0.05) for spike and block jump differences as well as 20-m sprint time. The large aerobic component of elite volleyball play was supported by the high VO2 max value recorded for the national team players (56.7 vs 50.3 ml kg-1 min-1). The results suggest that either years of specific physical conditioning and playing or the selection of individuals for the national team who possess more desirable characteristics as a consequence of genetic endowment, plays a significant role in the preparation of international calibre volleyball players. PMID- 1588684 TI - Progress in sports science. PMID- 1588685 TI - The influence of the site of sampling and assay medium upon the measurement and interpretation of blood lactate responses to exercise. AB - This paper reports the findings of two investigations into methodological problems associated with the interpretation of blood lactate (BLa) in the sports sciences. In Experiment 1, brachial artery (A), antecubital venous (V) and fingertip capillary (C) blood samples were drawn simultaneously from nine subjects (mean age 21.1 +/- 1.3 years) during an incremental treadmill protocol and immediately assayed for BLa concentration. Experiment 2 investigated the extent of lactate concentration differences in whole blood (WB), lysed blood (LB) and plasma (P) measured using a YSI 23 AM analyser. In Experiment 1, a comparison of the mean BLa concentrations obtained from the three sites revealed no significant differences (P greater than 0.05). Correlations between BLa samples from different sites were very high, with r values ranging from 0.858 to 0.983. In Experiment 2, the mean lactate concentrations were: WB, 4.7 +/- 2.7 mM; LB, 5.0 +/- 3.0 mM; P, 7.0 +/- 3.8 mM. Plasma (P) values were significantly higher than WB and LB. Values from all sites were highly correlated with coefficients ranging from 0.963 to 0.987. IN CONCLUSION: (1) Significant arterial and venous BLa concentration differences do not exist during incremental treadmill exercise. (2) As capillary BLa concentrations reflect arterial values, their use in laboratory and field settings is recommended. (3) Lactate concentration differences in whole blood, lysed blood and plasma will influence the assessment of performance at fixed lactate reference values. (4) If the inter-laboratory test procedures are to be standardized and results compared, precise reporting of lactate sampling and assay techniques is critical. PMID- 1588686 TI - Avoiding ambiguity in the sonographic determination of the direction of umbilical cord twists. AB - The helical twisting pattern of umbilical cord vessels is a well-recognized phenomenon, and the direction of twisting can be easily determined by gross pathologic inspection. With the cord held vertically, vessels along the anterior surface that spiral downward from high left to low right, angled like the left side of the letter V, indicate a left helix. Those angled like the right side of the V form a right helix. However, confusion can occur in determining the direction of spiraling on prenatal sonographic images depending on whether the image plane transects the cord along the surface toward or away from the observer. For correct identification of the direction of the cord twist, images must be obtained along the nearer surface. PMID- 1588687 TI - Sensitivity of routine ultrasonographic screening for congenital anomalies during the last 5 years. PMID- 1588688 TI - Development of spontaneous echocardiographic contrast after surgical trauma. AB - To determine if hypercoagulability is associated with contrast, surgical trauma was studied in a canine model. Contrast increased in the right heart and aorta after laparotomy, but not after anesthesia alone in either the right or the left heart. The inferior vena cava had the largest amount of contrast after surgery, implying that contrast development was primarily a local response to injury. The cellular composition of this contrast was not determined, but it occurred in the absence of changes in systemic rheologic or hematologic parameters and was not affected by heparin administration. PMID- 1588689 TI - Milk of calcium in renal cysts: new sonographic features. AB - Milk of calcium (MOC) in a small renal cyst or calyceal diverticulum is quite common. Ninety-one small renal cysts with MOC in 61 patients were found within a period of 4 years and 7 months. The main sonographic features are echogenic material layering in the dependent portion of a cyst, associated with reverberation echoes without shadowing. Shadowing was seen when MOC was present in larger amounts. Because MOC is usually asymptomatic and requires no treatment, differentiation from other lesions such as calculi or angiomyolipomas is important for proper patient management. MOC is detected more readily by ultrasonography than by radiography or CT. PMID- 1588690 TI - Acute appendicitis confined to the appendiceal tip: evaluation with graded compression sonography. AB - Focal appendicitis at the tip of the appendix has not been emphasized in the sonographic literature. We present the sonographic findings in four patients with pathologically confirmed acute appendicitis confined to the appendiceal tip. In all four patients, the base of the appendix had a normal appearance with maximal outer diameters measuring 4 to 6 mm. However, the inflamed tip was focally enlarged, measuring greater than 7 mm. The importance of a careful survey of the entire length of the appendix is emphasized to avoid a false-negative examination. PMID- 1588691 TI - Sonography of acute appendicitis in childhood: perforation versus nonperforation. AB - We evaluated the sonographic findings in 133 consecutive children referred for suspected appendicitis. Fifty-eight of these patients (44%) ultimately underwent surgery, with 54 of these proved to have acute appendicitis. Thirty-one (58%) of the 54 had nonperforated appendicitis, and 23 (43%) had evidence of perforation. Previously described sonographic findings that have been employed in the diagnosis of appendicitis were evaluated, with the presence or absence of these findings being compared in patients with non-perforated and perforated appendicitis. In those patients who did not undergo surgery, the following findings were documented and compared to the findings in patients with proved appendicitis: (1) an identifiable appendix and its sonographic characteristics, (2) fluid localized to the right peritoneal reflection or periappendiceal region, or both, (3) free pelvic fluid, and (4) right lower quadrant adenopathy. Our results suggest that high-resolution, real-time sonography, using graded compression, is very sensitive in the identification of acute nonperforated appendicitis. Perforated appendicitis, however, can be a more difficult diagnosis because the appendix frequently decompresses with perforation and yet may not "wall off" or form a well-defined abscess. As a result, the appendix can be very difficult to identify. PMID- 1588692 TI - Evaluation of PACS in ultrasonography. AB - We review our experience with a picture archiving and communication system to replace film in the ultrasound section of a clinical radiology department. The system includes three ultrasound units connected by a fiberoptic network via acquisition nodes to a central data management system, workstation, and optical jukebox. The system handles 80% of sonographic studies in the department. Image production, interpretation, storage, and retrieval are evaluated. Despite limitations, a picture archiving and communication system can be integrated into a functioning ultrasound section of an active radiology department with minimal disruption and promising results. PMID- 1588693 TI - 3-dimensional sonographic analysis based on color flow Doppler and gray scale image data: a preliminary report. AB - This paper presents preliminary results of a technique that permits acquisition and display of three-dimensional (3D) anatomy using data collected from color flow Doppler and gray scale image sonography. 3D sonographic image data were acquired as two-dimensional planar images with commercially available equipment. A translational stage permitted the transducer position and orientation to be determined. Color flow sonographic video image data were digitized into a PC-AT computer along with transducer position and orientation information. Color flow velocity and gray scale data were separated, 3D filtered, and thresholded. A surface rendering program was used to define the vessel blood-lumen interface. Planar slices of arbitrary orientation and volume rendered images were displayed interactively on a graphics workstation. The technique was demonstrated in a lamb kidney in vitro and for the carotid artery at the bifurcation in vivo. Our results demonstrate the potential of 3D sonography as a technique for visualization of anatomy. Color flow data offer direct access to the vascular system, facilitating 3D analysis and display. 3D sonography offers potential advantages over existing diagnostic studies in that it is noninvasive, requires no intravenous contrast material, offers arbitrary plane extraction and review after the patient has completed the examination, and permits vascular anatomy to be visualized clearly via rendered images. PMID- 1588694 TI - Delayed return of the fetal midgut to the abdomen resulting in volvulus, bowel obstruction, and gangrene of the small intestine. PMID- 1588695 TI - Renal hemangiopericytoma in childhood: noninvasive imaging. PMID- 1588696 TI - Hemimegalencephaly. Cranial sonographic findings. PMID- 1588697 TI - Fetal growth retardation due to massive subchorionic thrombohematoma: report of two cases. PMID- 1588698 TI - Sonographic diagnosis of an incarcerated inguinal hernia containing uterus and left adnex A. PMID- 1588699 TI - Variation in second trimester fetal growth and sonographic determination of gestational age. PMID- 1588700 TI - Guns, drugs threaten to raise public health problem of violence to epidemic. PMID- 1588701 TI - Congress acts to resuscitate nation's financially ailing trauma care systems. PMID- 1588702 TI - Attacks on homosexual persons may be increasing, but many 'bashings' still aren't reported to police. PMID- 1588703 TI - From the Assistant Secretary for Health, US Public Health Service. PMID- 1588704 TI - From the Surgeon General, US Public Health Service. PMID- 1588705 TI - From the Centers for Disease Control. Firearm-related deaths--Louisiana and Texas, 1970-1990. PMID- 1588706 TI - From the Centers for Disease Control. Physical fighting among high school students--United States, 1990. PMID- 1588707 TI - Firearm access and suicide. PMID- 1588708 TI - Final exit and the risk of suicide. PMID- 1588709 TI - Roe v Wade was followed by a decrease in neonatal homicide. PMID- 1588710 TI - Death certificate reporting of colon and rectal cancers. PMID- 1588711 TI - Secretory otitis media: the Cantekin affair. PMID- 1588712 TI - Secretory otitis media: the Cantekin affair. PMID- 1588713 TI - Secretory otitis media: the Cantekin affair. PMID- 1588714 TI - Secretory otitis media: the Cantekin affair. PMID- 1588715 TI - Secretory otitis media: the Cantekin affair. PMID- 1588716 TI - Loaded guns in the home. Analysis of a national random survey of gun owners. AB - OBJECTIVE: To identify factors associated with keeping guns loaded. Four hypotheses were tested: that people are more likely to keep their firearms loaded if (1) the primary reason for owning a gun is protection, (2) the gun is a handgun, (3) there are no children in the household, or (4) the gun owner has not received training in the proper use of firearms. DESIGN AND SETTING: A random national telephone survey of gun owners conducted in December 1989. A screening question was used to identify individuals as gun owners. Participants were called at home. PARTICIPANTS: 605 individuals (approximately two thirds of the population contacted) participated in the survey. All were 18 years and older, most were men (64%), and a few were nonwhite (12%). The majority owned more than one gun (77%). RESULTS: Three of the four hypotheses were substantiated by the data. Handgun owners (odds ratio [OR], 2.17; 95% confidence interval [CI], 1.67 to 2.82), individuals who owned a firearm principally for protection (OR, 1.65; 95% CI, 1.30 to 2.11), and people who lived in households without children (OR, 1.42; 95% CI, 1.13 to to 1.82) were all more likely to keep a gun loaded than other individuals. Instruction in the proper use of firearms did not seem to affect the probability of keeping guns loaded (OR, 0.86; 95% CI, 0.69 to 1.07). CONCLUSIONS: The spontaneous nature of many firearm deaths has led to speculation that a substantial proportion of firearm-related morbidity and mortality could be prevented if easy access to loaded weapons were reduced through appropriate storage practices. Our findings show that a significant proportion of gun owners disregard basic safety procedures. However, without information on the specific content of safety instruction, we cannot say that education about safe storage practices is ineffective. PMID- 1588717 TI - Urban high school youth and handguns. A school-based survey. AB - OBJECTIVE: To determine the prevalence of handgun ownership among urban high school youth and investigate associations with socioeconomic status, ethnicity, and deviant behaviors. DESIGN: Survey of half of the Seattle, Wash, public high schools, which enroll 50% of the school district's 11th-grade students (N = 970). MAIN OUTCOME MEASURES: Self-reports of handgun ownership, perceived access to handguns, racial/ethnic identity, social status (Hollingshead's Two Factor Index of Social Position), and social deviance (Seattle Self-Report Instrument) were determined. RESULTS: Thirty-four percent of the students reported easy access to handguns (47% of males, 22% of females) and 6.4% reported owning a handgun (11.4% of males, 1.5% of females). Reported firearm experiences indicated a high rate of handgun utilization: 33% of handgun owners had fired at someone, 9.7% of female students reported a firearm homicide or suicide in family members or close friends, and 6% of male students reported carrying a handgun to school sometime in the past. Handgun ownership was more common among students who reported deviant behaviors. Adjusting for age, gender, and racial/ethnic group and controlling for covariation among the problem behaviors, gang membership (odds ratio [OR], 8.8; 95% confidence interval [CI], 3.7 to 20.8), sentencing by a judge (OR, 4.6; 95% CI, 1.3 to 15.5), selling drugs (OR, 3.7; 95% CI, 1.8 to 7.8), suspension or expulsion from school (OR, 3.5; 95% CI, 1.7 to 7.0), and assault and battery (OR, 2.5; 95% CI, 1.1 to 5.9) were associated with handgun ownership. However, 22% of male handgun owners did not report any of the above behaviors. CONCLUSION: The availability of handguns to the urban high school students surveyed is pervasive, and it is not limited to high-risk groups. PMID- 1588718 TI - Weapon involvement and injury outcomes in family and intimate assaults. AB - OBJECTIVE: To compare the risk of death and the risk of nonfatal injury during firearm-associated family and intimate assaults (FIAs) with the risks during non firearm-associated FIAs. DESIGN: Records review of police incident reports of FIAs that occurred in 1984. Victim outcomes (death, nonfatal injury, no injury) and weapon involvement were examined for incidents involving only one perpetrator. SETTING: City of Atlanta, Ga, within Fulton County. PARTICIPANTS: Stratified sample (n = 142) of victims of nonfatal FIAs, drawn from seven nonfatal crime categories, plus all fatal victims (n = 23) of FIAs. MAIN OUTCOME MEASURES: Risk of death (vs nonfatal injury or no injury) during FIAs involving firearms, relative to other types of weapons; risk of nonfatal injury (vs all other outcomes, including death) during FIAs involving firearms, relative to other types of weapons. RESULTS: Firearm-associated FIAs were 3.0 times (95% confidence interval, 0.9 to 10.0) more likely to result in death than FIAs involving knives or other cutting instruments and 23.4 times (95% confidence interval, 7.0 to 78.6) more likely to result in death than FIAs involving other weapons or bodily force. Overall, firearm-associated FIAs were 12.0 times (95% confidence interval, 4.6 to 31.5) more likely to result in death than non-firearm associated FIAs. CONCLUSIONS: Strategies for limiting the number of deaths and injuries resulting from FIAs include reducing the access of potential FIA assailants to firearms, modifying firearm lethality through redesign, and establishing programs for primary prevention of violence among intimates. PMID- 1588719 TI - Firearm and nonfirearm homicide among persons 15 through 19 years of age. Differences by level of urbanization, United States, 1979 through 1989. AB - OBJECTIVE: To examine trends (1979 through 1989) and current status in firearm and nonfirearm homicide rates by level of urbanization among persons 15 through 19 years of age. DESIGN: The Compressed Mortality File, a county-level mortality and population database maintained by the National Center for Health Statistics, Centers for Disease Control, Hyattsville, Md, and the 1980 Human Resource Profile County Codes are used to analyze age-, sex-, and race-specific firearm and nonfirearm homicide rates by urbanization level. SETTING: United States, 1979 through 1989. SUBJECTS: Black and white males and females 15 through 19 years of age whose underlying cause of death was either firearm homicide (E965.0 through E965.4 or E970) or nonfirearm homicide (E960 through E964, E965.5 through E969, or E971 through E978) in the ICD-9 (International Statistical Classification of Diseases, Injuries, and Causes of Death, Ninth Revision). MAIN OUTCOME MEASURES: Urbanization level-specific firearm and nonfirearm homicide rates. RESULTS: The 1989 firearm homicide rate in metropolitan counties was nearly five times the rate in nonmetropolitan counties (13.7 vs 2.9 deaths per 100,000 population). Firearm homicide rates were highest in core metropolitan counties, 27.7 per 100,000 population; rates were higher for black males than for any other race-sex group in each of five county urbanization strata for 1979 through 1989. Nonfirearm homicide rates are considerably lower, with smaller urban differentials; the rate in metropolitan counties was 1.4 times the rate in nonmetropolitan counties (2.6 vs 1.8 per 100,000 population). From 1979 through 1984, firearm homicide rates declined in each of the county strata. From 1984 through 1987, firearm homicide rates increased, and from 1987 through 1989 they increased rapidly, from 23% to 35% per year in the four metropolitan strata. From 1979 through 1989, nonfirearm homicide rates declined or remained stable. CONCLUSIONS: Large urbanization differentials in firearm homicide and smaller differentials in nonfirearm homicide are identified. Firearm homicide rates are highest and increasing the fastest among black teenage males in the core, fringe, and medium metropolitan strata. PMID- 1588720 TI - Television and violence. The scale of the problem and where to go from here. PMID- 1588721 TI - Male victims of sexual assault. AB - OBJECTIVE: To compare the demographics, physical findings, and assault characteristics of incarcerated, sexually assaulted men with those of nonincarcerated, sexually assaulted men. DESIGN: Case series of 99 adult male victims of sexual assault evaluated over a 3-year period. SETTING: Memphis Sexual Assault Resource Center, a nonhospital-based clinic that serves as the primary resource for sexually assaulted victims in the Memphis and Shelby County, Tennessee, area. PARTICIPANTS: All adult male victims of sexual assault evaluated at the Memphis Sexual Assault Resource Center during the study period were included in the study. Ninety-nine victims were studied, including 80 incarcerated men and 19 men from the community. RESULTS: The victims of sexual assault in the community group were older than the victims in the incarcerated group. Apart from the age difference and weapon use, there were no statistically significant differences between the incarcerated and nonincarcerated victims. CONCLUSIONS: The similarities between the two groups suggest that sexual assault of men may not be unique to prisons, and all men are potential victims. Further studies are required to better understand these crimes and to develop education and prevention programs. PMID- 1588722 TI - Assault weapons as a public health hazard in the United States. Council on Scientific Affairs, American Medical Association. PMID- 1588723 TI - Let's be clear. Violence is a public health problem. PMID- 1588725 TI - Letter from Trincomalee. Innocence abroad. PMID- 1588724 TI - The Firearm Fatality Reporting System. A proposal. PMID- 1588726 TI - A piece of my mind. Knife and gun clubs of America. PMID- 1588727 TI - [Rheumatoid arthritis--general concepts]. AB - It is most important to recognize that Rheumatoid Arthritis (RA) is a multiple organ disease, and not a disease restricted only to the joint and muscle. RA is one of the collagen diseases or connective tissues diseases, and the pathogenesis is still not clear but an autoimmune phenomenon should be related with the genesis of the disease and a genetic background might be correlated. In this paper, the general concepts on RA are described from (1) the position of RA in collagen disease, connective tissue disease, autoimmune disease or auto-allergic disease and rheumatic disease, (2) recognition of pathophysiological and clinical figure of RA as a whole body disorder, (3) the procedures for diagnosis in various types of RA and (4) considerations of the treatment. PMID- 1588728 TI - [Contribution of genetic factors to RA]. AB - Multiplex families of rheumatoid arthritis (RA) and concordance of the development of RA in monozygotic twins strongly suggest the relationship of genetic factor to the onset of RA. Among many genetic markers, HLA shows the strongest association with RA and association between RA and HLA-DR4 has been reported in many ethnic groups. DNA typing of HLA class II genes revealed that DRB1 * 0405 (Dw 15) is the most susceptible DRB1 allele for RA in the Japanese. The particular epitope sequence at the third hypervariable region (position 70 74, and 86) and DR beta chain, expressed with the structure of the DR4 molecule seems to be important for the susceptibility to RA. PMID- 1588729 TI - [Possible roles of infections and heat shock proteins in rheumatoid arthritis]. AB - Heat shock protein, one of the most conserved proteins from prokaryotes to man, was shown to be strongly immunogenic in bacterial and helminthic infections. Evidences have accumulated suggesting that mycobacterial hsp65 plays a crucial role in the development of adjuvant arthritis induced in rats. By analogy, the pathogenetic roles of hsp were investigated in rheumatoid arthritis in man. The evidences obtained so far are highly suggestive but still circumstantial. Hsp's strong immunogenicity and high conservation, which seem to be mutually exclusive, make this molecule very mysterious. In this regard, Coutinho's new network theory or Cohen and Young's theory of immunological homunculus nicely reconciles these aspects. PMID- 1588730 TI - [Aberrant expression of adhesion molecules in rheumatoid arthritis]. AB - The regulation of lymphocyte migration to specific tissues is complex and involves lymphocyte-endothelial interactions at sites of extravasation. Adhesion molecules play a vital role in the migration of lymphocyte into and out of the tissues. Therefore, excessive induction of adhesion molecules on the vascular endothelium might result in the accumulation of lymphocytes in the rheumatoid synovium. The rheumatoid synovium exhibits functionally as well as morphologically altered synovial vessels, which are probably induced by inflammatory mediators. It should be pointed out that the immunocompetent cells confront various extracellular matrix after extravasation. The signalling through receptors for extracellular matrix modify the subsequent cellular responses against certain target tissues. Thus, interaction of immunocompetent cells with endothelium as well as extracellular matrix through adhesion molecules is critical for the pathogenesis of rheumatoid arthritis. PMID- 1588731 TI - [Histamine receptors in arthritis]. AB - Histamine H1 and H2 receptors in lymphocytes, bone marrow mononuclear cells, synovial fibroblasts and chondrocytes were measured by binding assay and pharmacological study. Histamine suppressed IgG production through H1 and H2 receptors and cytotoxic activity through H2 receptor in lymphocyte. Histamine increased the production of hyaluronic acid in synovial fibroblast through H1 and H2 receptors. In the production of keratan sulfate in the chondrocyte, histamine increased through H1 receptor and decreased through H2 receptor. In arthritis, the functions of H2 receptor in the lymphocyte, bone marrow mononuclear cell and synovial fibroblast were decreased, and the function of H1 receptor in the chondrocyte was decreased. On the other hand, histamine content was reported to increase in synovial fluid with RA. Our data indicate histamine had suppressive effects on IgG production and cytotoxic activity, but the functions of histamine receptors, especially H2 receptor, were decreased in RA. The beneficial effects of histamine in RA synovial fluid might therefore be decreased by hypofunction of the H2 receptor. These data suggest that abnormalities in histamine receptors in arthritis could be involved in perpetuating the inflammatory process in RA. PMID- 1588732 TI - [Cytokines and chemical mediators in rheumatoid arthritis]. AB - Multiple chemical mediators are constitutively produced from rheumatoid synovium resulting in joint destruction. These include arachidonic acids metabolites such as prostaglandins and leukotrienes, vasoactive amines, kinins, endothelins, complement fragments, reactive oxygens, neutral proteinases and cytokines. Among cytokines, interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor (TNF), platelet-derived growth factor (PDGF), GM-CSF, M-CSF are known to be constitutively produced from inflammatory synovium. Most of these cytokines are mainly produced from synovial cells which are recruited and/or proliferated in the synovium. The mechanism of inducing or aggravating joint destruction with these cytokines and other chemical mediators is discussed. PMID- 1588733 TI - [Biotechnology for rheumatology researches]. AB - Recent developments in biotechnology include cellular engineering and molecular engineering. In order to further investigate several aspects of rheumatic diseases, it is necessary to know and apply these new techniques. They are, for example, monoclonal antibody productions, T cell lines, T cell hybridomas, gene cloning, Southern blot, Northern blot, recombinant protein productions and PCR. Out lines of these techniques are described. PMID- 1588734 TI - [Clinical evaluation and application of new ARA criteria for rheumatoid arthritis]. AB - At the 51st American Rheumatism Association meeting, a new ARA criteria for rheumatoid arthritis (RA) was proposed. According to this criteria, both the sensitivity and the specificity have improved to 93% and 90%, respectively. We investigated the adequacy of this criteria by applying this to Japanese patients with RA and control subjects with rheumatic diseases, other than RA. By using new criteria the sensitivity was decreased from 89.6% to 85.3% and the specificity was increased from 82.7% to 92.8%. The factors for the decreased sensitivity of the new criteria were 1) morning stiffness which became more than 1 hour, 2) the number of swelling joints increased from one to three and 3) radiologic changes, which were restricted to the hand only. On the other hand, the factors for increased specificity were (1) morning stiffness, (2) deletion of criterion of joint pain and (3) joint swelling. According to the classification tree method, the sensitivity and the specificity were 96.3% and 90.0% respectively in this study. Continued nationwide study on this new criteria, whether this is applicable and useful to classify Japanese patients with RA is necessary. PMID- 1588735 TI - [Imaging modalities of rheumatoid arthritis]. AB - Modern diagnostic techniques for rheumatoid arthritis include x-ray examination, arthro- or myelography, CT scan, scintigraphy, thermography, ultrasonography, and MRI. X-ray is the simplest and most common method for assessing the degree of joint destruction. Arthrography provides information on intra-articular pathology. CT is particularly of value in visualizing changes in the axial skeleton. Joint scintigraphy, using 99m-technetium pertechnetate, is available in evaluating the degree of synovial inflammation. Thermography has been performed for a similar purpose. Ultrasound allows a real-time, dynamic study of soft tissues in and around the joint, including tendons, synovium and articular cartilage. MRI most clearly shows various pathological conditions such as pannus, degenerated cartilage or spinal cord compression, although the examination time should be shortened. PMID- 1588736 TI - [Diagnosis of rheumatoid arthritis--using biochemical technique]. AB - Rheumatoid arthritis is a systemic disease. Onset of the disease occurs most often between the ages of 20 and 60 years with a peak at 30 and 50 years. The diagnosis of rheumatoid arthritis (RA) is usually based on the revised criteria for the classification of RA. The presence of 4 or more of 7 criteria defines "rheumatoid arthritis". There is today much interest in development of a biochemical "marker" of RA, to detect the early phase of RA. Some approach employs measurement of serum and joint fluid levels of articular cartilage macromolecules, antibodies, and so on. In the section, we would like to describe some materials available now. It is difficult to point out a single material superior to rheumatoid factor to make a diagnosis of RA at the present time. PMID- 1588737 TI - [Immunological and serological tests useful for diagnosis of rheumatoid arthritis]. AB - There are four areas of laboratory medicine engaged in the diagnosis of rheumatoid arthritis. They are serological tests for diagnosis of infection, tests for autoantibodies, analysis of serum proteins and lymphocyte function tests, including surface markers. In these areas except for diagnosis of infection, marked development has been achieved in the recent ten years. Enumerating roughly, I like to point out quantitative tests of rheumatoid factor, precise examinations for antinuclear antibodies, recent method for electrophoresis of serum protein and monoclonal antibodies for lymphocyte surface markers. Diagnosis of rheumatoid arthritis has became more precise and reliable by using these laboratory tests. In addition, effective tools are available to approach pathogenesis of rheumatoid arthritis through management of RA patients. An outline of these recent laboratory tests, useful for diagnosis of rheumatoid arthritis is presented. PMID- 1588738 TI - [Glucocorticoids]. AB - Recent years have witnessed the reassessment of cotherapy with steroid preparations and antirheumatic agents for the treatment of rheumatoid arthritis. However, in addition to desirable anti-inflammatory and immunosuppressive properties, the pharmacological spectrum of glucocorticoids includes diverse activities which may result in numerous adverse reactions. Antirheumatic therapy therefore requires strict adherence to the prescribed indications and careful selection of the specific drug type and dosage regimen. Based on the patient's response, dose reduction or withdrawal of any steroid preparations should be attempted. Although antirheumatic and non-steroidal anti-inflammatory agents are the mainstay treatment for rheumatoid arthritis, steroid therapy is usually employed when these drugs are not sufficiently effective. PMID- 1588739 TI - [NSAIDs (non steroidal anti-inflammatory drugs) for the treatment of rheumatoid arthritis]. AB - Non-steroidal anti-inflammatory drugs (NSAIDs) are often prescribed to patients with rheumatoid arthritis (RA), as the first line drugs, and are administered over a long term. NSAIDs are classified principally into acidic and basic preparations, and the former is more widely used for the treatment, since the latter possesses no anti-rheumatic effect. Moreover, the acidic NSAIDs are classified into salicylates, arylacetic acid, pyrazolone, fenamates and oxicams. Arylacetic acid has a strong analgesic effect. Pyrazolone is well balanced between analgesic, anti-inflammatory and antifebrile effects. The fenamates and oxicams are long acting. On the other hand, NSAIDs sometimes inhibit adverse reactions, such as gastroduodenal diseases and renal insufficiency, which are probably induced by the inhibition of cyclo-oxygenase to reduce prostaglandin content. Therefore, appropriate NSAIDs must be selected after consideration on the character, property and adverse reaction of each drug. PMID- 1588740 TI - [Gold compounds and D-penicillamine for therapy of rheumatoid arthritis]. AB - Rheumatoid arthritis is a severe disease and it is difficult to prevent the progression of disease. Gold compounds (injectable gold and oral gold) and D penicillamine (D-PA) have the possibility to retard joint destruction and to slow radiological progression. These drugs are called Disease Modifying Antirheumatic Drugs (DMARD), and they should be tried in cases resisting conventional NSAID's therapy. They are effective in more than 60% in severe rheumatoid patients but they also have many side effects, e.g. eczema, skin rash, renal dysfunction, aplastic anemia. Laboratory checks should be carried out once a month during the first six month, and every 2 or 3 months thereafter. To compare injectable gold with D-PA, discontinuation due to inefficacy of D-PA is higher than with injectable gold, but side effects of injectable gold is greater. Oral gold is less effective than the other 2 drugs, but has a lower rate of side effects. PMID- 1588741 TI - [Immunosuppressant and immunomodulator]. AB - Rheumatoid arthritis (RA) is characterized by deforming, destructive joint disease. It also accompanies multiple extra-articular symptoms. Although initial agent (s) has not been clearly delineated, understandings of joint destruction mechanism have made considerable progress. Initial rheumatoid inflammation takes a form of the proliferation of synovial lining cells and the perpetuation of inflammation leads to cartilage and bone destruction. These pathologic changes are mediated by immunological aberration. On the basis of these observations, suppression and/or modulation of such immunological aberration may be reasonable alternative way of treating patients with RA. Recent knowledge and several topics of immuno-suppressant and-modulator were introduced. Such immunotherapies are indicated in patients with early active RA but rather frequent occurrence of side effects makes us use cautiously such drugs. PMID- 1588743 TI - [Intra-articular injection therapy in patient with rheumatoid arthritis]. AB - For RA, intra-articular injection therapy can be said to be a bridge between systemic therapies, such as pharmacotherapy and rehabilitation, and invasive treatment such as arthroplasty. Precise intra-articular injection with strict aseptic procedure and understanding of joint anatomy is required. Drugs to be injected include steroids, aiming at anti-inflammation and analgesia, and radioisotope and osmate, aiming at synovectomy. Injection is indicated in cases in which pharmacotherapy is ineffective and too early for arthroplasty. Unnecessary frequent injections may increase joint destruction and make proper timing of the operation difficult. Injection should be performed with full understanding of the advantages and disadvantages of RA therapy. PMID- 1588742 TI - [Development of new drugs for the treatment of rheumatoid arthritis]. AB - Development of new drugs for the treatment of rheumatoid arthritis (RA) can be classified into two categories: one is modification and improvement of the drugs being used now and the other is development of more effective drugs which are being developed by virtue of progress in immunology and molecular biology. The author describes the present status of the treatment of RA and its future trend: anti-rheumatic and anti-inflammatory drugs which may be developed in the near future, recent progress in prodrugs of NSAID, cytokine antagonists, particularly for IL-1, and more specific immunological approaches to the treatment of RA. It is hoped that these potential anti-rheumatic drugs will be developed in next the 10-20 years. PMID- 1588744 TI - [Surgical treatment of rheumatoid arthritis]. AB - Synovectomy, total arthroplasty and arthrodesis are the main surgical methods for rheumatoid arthritis. Although recurrent synovitis and radiological deterioration after synovectomy have been reported, the procedure can be an effective treatment if it is performed in the early stage where articular cartilage and bone are minimally damaged. Arthrodesis is indicated for severely destroyed joints. However, since loss of motion in the proximal joints often leads to severe disability, its indication is limited to the distal joints, such as the wrist and ankle. Total rthroplasty seems to be an ideal method because relief of pain and recovery of function can be obtained simultaneously. However, there are some complications, such as loosening and wear of the prosthesis. Solution of these would bring much benefit to the disabled rheumatoid arthritis patient. PMID- 1588745 TI - [Plasmapheresis for patients with RA]. AB - Effect of plasmapheresis for patients with rheumatoid arthritis. Plasmapheresis for rheumatoid arthritis (RA) was performed more than ten years, but efficacy of plasmapheresis was not done. In this paper, we discussed efficacy, indications and procedures. We have many procedures of plasmapheresis, 1) plasma exchange, 2) double filtration plasmapheresis, 3) cryofiltration plasmapheresis, 4) immunoadsorption plasmapheresis, 5) salt-amino acid coprecipitation plasmapheresis, 6) lymphocytapheresis, 7) lymphocyte-plasmapheresis, 8) photopheresis. Indications of plasmapheresis for RA are 1) malignant RA, 2) high activity of RA, 3) positive circulating immune complexes, 4) patients can't take steroid hormone or anti-inflammatory drugs. Efficacy of plasmapheresis for RA was not done, then, we must have controlled study about efficacy of plasmapheresis for RA. PMID- 1588746 TI - [Rehabilitation in rheumatoid arthritis]. AB - In the patient with rheumatoid arthritis, muscle weakness and joint contracture and deformity develop, despite the most carefully directed programs of medical care. At the acute phase of this disease, the immobilization or stabilization of arthritic joints is effective for the improvement of inflammation without risk of contracture. At the chronic phase, the patients should be carefully instructed as to the importance of the joint mobility exercise and muscle strengthening exercise. Finally, we must consider that patients with rheumatoid arthritis suffer not only from painful joints but also from psychological and socio economical damage. PMID- 1588747 TI - [Improvement of ADL and quality of life ]. AB - Improvement of quality of life (QOL) of the patients with rheumatoid arthritis (RA) is very important. Practically, health status measurement (HSM) is beneficial to the assessment of QOL in arthritides, because the socioeconomical factor, one of 3 main factors in QOL, has numerous matters besides the medicine. There are many scales to assess health status so far, Health Assessment Questionnaire (HAQ) and Arthritis Impact Measurement Scales (AIMS) have been widely utilized because of their reliability, validity and sensitivity. We compared the health status in 105 of RA inpatients and that in 86 of RA outpatients by AIMS. Outpatients had significantly better physical status than inpatients. Our data showed a great discrepancy from that of Anderson. The reason for this discrepancy is presumably the differences in life style and daily activity between two countries. We are now trying to modify AIMS to fit Japanese. PMID- 1588748 TI - [Psychosomatic medicine in rheumatoid arthritis]. AB - Recent studies have shown that neuropeptides, such as substance P, are responsible for arthritis. We therefore studied opioid peptides (beta-endorphin, Methionine-enkephalin, Leucine-enkephalin) in order to confirm our belief that mental status may have some influence on the activity of rheumatoid arthritis (RA). We examined opioid peptides, lymphocyte subsets, psycologic test (Cornell Medical Index-Health questionnaire (CMI), the Face scale) and clinical data in patients with RA. Plasma Leu-enk, % Leu2a+ Leu15- cells,% Leu3a+ Leu8- cells and % Leu11+ Leu7- cells were higher in patients with a larger number of psycologic complaints in CMI. Plasma Leu-enk concentration was higher while % Leu11+ Leu7- cells was lower in proportion to the degree of neurosis, as indicated by the descrimitive chart of CMI. Plasma Met-enk concentration, % Leu2a+ Leu15- cells, and Lansbury's index were significantly higher in the group of patients whose facial expression was more severe. These findings suggest that mentala status have some relationship with the plasma level of opioid peptides (enkephalins) and immunologic functions, and that it may exert indirect effects on RA. PMID- 1588749 TI - [Physical therapy and Oriental medicine applied to rheumatoid arthritis]. AB - Since the etiology of rheumatoid arthritis is unknown, etiological treatment of this disease is impossible. The most important thing is how to prevent joint destruction and maintain function. Physical therapy and Japanese oriental medicine therapy are highly useful in that meaning. In this article, heat & cold therapy, light therapy, massage, and acupuncture and moxibustion are discussed from the viewpoint of the methods of application, as physical therapy. Japanese herb medicine is also discussed along with general medicine. PMID- 1588750 TI - [Cardiac and pulmonary manifestations in rheumatoid arthritis]. AB - Pericarditis may be the most common cardiac manifestation in RA patients and the incidence in autopsy cases is more than 30%. Pericardial effusion shows low sugar and complement level and high level of LDH and gamma-globulin. The administration of corticosteroids has been successfully used in the treatment of rheumatoid pericarditis. The pulmonary involvement in RA include pleuritis, nodules and interstitial lung disease. Interstitial lung disease in RA patients appears to run a continuum from mild pneumonitis to severe pulmonary fibrosis and occasionally it include bronchiolitis obliterans organizing pneumonia (BOOP) which is sensitive to corticosteroid therapy. Although open lung biopsy is the definitive procedure for proving the diagnosis of interstitial lung disease, open lung is now being complemented or replaced by transbronchial lung biopsy and bronchoalveolar lavage (BAL). Corticosteroids will be effective to BOOP definitely and in general usual interstitial pneumonia (UIP) is resistant to treatment. In addition to the primary pulmonary manifestations of RA, anti rheumatic drug reactions in the lung may be associated. PMID- 1588751 TI - [Renal disorders in rheumatoid arthritis]. AB - Glomerulonephritis has been believed to be a rare complication in rheumatoid arthritis (RA). However, recent studies have revealed a focal segmental increase in mesangial cells and matrix in RA patients with hematuria. In our series, proteinuria, hematuria or both abnormalities were recognized in 74 (22%) out of 336 RA cases. Among 119 patients examined by renal biopsy, mild mesangial proliferative glomerulonephritis (GN) was found in 25 patients, of which 22 demonstrated mesangial IgA deposits, by immunofluorescent microscopy. Membranous nephropathy was noticed in 26 cases. Three cases of membranous nephropathy had no history of gold or D-penicillamine treatment. Electron microscopy revealed diffuse thinning of the glomerular basement membrane in 12 cases. The average thickness of the glomerular basement membrane was significantly thinner in RA patients than in normal subjects. The immunological processes associated with rheumatoid factor do not seem to be related to the renal lesions in RA patients. PMID- 1588752 TI - [Hematologic abnormalities associated with rheumatoid arthritis]. AB - Anemia is frequently found in patients with rheumatoid arthritis (RA) and is the most common extra-articular manifestation RA. The majority of patients with RA have a mild normocytic hypochromic anemia which correlates with the erythrocyte sedimentation rate and with activity of the disease. White blood cell counts are usually in the normal range or only slightly elevated. The differential white blood cell count is usually within normal limits. Eosinophilia and thrombocytosis are often associated with RA. Hematologic abnormalities of RA is correlated to the activity of the disease, and therefore the most important aspect of treatment lies in the general control of the chronic inflammation. PMID- 1588753 TI - [Amyloidosis in rheumatoid arthritis]. AB - Complication of secondary amyloidosis is becoming an important problem in the management of rheumatoid arthritis in Japan, because patients with rheumatoid arthritis, complicated by amyloidosis, have been increasing recently and the prognosis is poor in most cases. Renal and gastrointestinal symptoms are cardinal features of amyloidosis in rheumatoid arthritis, and most of these patients die of renal failure or cachexia, based on gastrointestinal involvement, within several years. Diagnosis in the early stage is recommended for good management of amyloidosis in rheumatoid arthritis, and gastroscopic biopsy appears to be the most available method for early diagnosis of amyloidosis. PMID- 1588754 TI - [Osteoporosis in rheumatoid arthritis]. AB - Rheumatoid arthritis may be associated with generalized, as well as, juxta articular osteoporosis. To assess the skeletal distribution of bone loss, bone mass was measured in women with rheumatoid arthritis, using single photon absorptiometry and dual energy X-ray absorptiometry. Bone loss was more rapid in the distal metaphyseal region of the radius than in the diaphyseal region. Bone loss in the legs was correlated with gait disturbance and bone loss in the third lumbar vertebra was recognized only in the patients treated with corticosteroids for more than 1 year. These results indicate that rheumatoid arthritis was not universally associated with generalized osteoporosis. Patients treated with corticosteroids are likely to be at risk from generalized osteoporosis. PMID- 1588756 TI - [Mutilans type of rheumatoid arthritis]. AB - In order to investigate the clinical and pathological features of arthritis mutilans, the clinical history, activity of inflammation, histological findings and treatment have been studied on the basis of follow-up of rheumatoid arthritis (RA) patients with arthritis mutilans. A high incidence of arthritis mutilans was observed in rheumatoid patients who have a younger onset, longer history and higher activity of RA without specific pathophysiological features. Joint destruction may further progress in arthritis mutilans despite intensive treatment with disease modifying anti-rheumatic drugs (DMARDs), and multi-joint replacement may be required in the patients with this type of arthritis. PMID- 1588755 TI - [Malignant rheumatoid arthritis]. AB - Malignant rheumatoid arthritis (MRA) is a name for rheumatoid arthritis (RA) complicated with systemic vasculitis or other severe extra-articular manifestations, which can cause a fatal outcome. MRA is found in 4-5% of inpatients with RA. The male to female ratio is 1:1.45. Histologically, 3 main types are recognised in rheumatoid vasculitis; RA type (vasculitis with rheumatoid nodule-like appearance), PN type (fibrinoid vasculitis similar to PN), and EA type (endoarteritis obliterans). High titers of rheumatoid factor, immune complexes, hypocomplementemia, hypoproteinemia, decreased choline esterase activity, elevated alkaline phosphatase activity and leukocytosis are characteristic laboratory features of MRA. Recently, it appears that MRA is becoming less and the prognosis is getting better, perhaps due to the advancement in treatment. PMID- 1588757 TI - [Clinical pictures of juvenile rheumatoid arthritis]. AB - Juvenile rheumatoid arthritis is a clinical syndrome of primary chronic arthritis in childhood. JRA is subdivided into three subtypes according to the clinical picture within six months of the onset of the disease. The clinical picture of systemic onset type usually starts with a characteristic spiking fever. Children with this onset type, sometimes have pleursy, percarditis, myocarditis, generalyzed lymphnode swelling, hepatosplenomegaly and rheumatoid rash, but arthritis may not appear within the first few months. Children with polyarticular onset type, joint manifestations are similar to that of the rheumatoid arthritis of the adult. In patients with the pauciarticular onset type, the prognosis of arthritis is relatively fair compared with the other two types, but the doctor must always be aware of the complication of chronic and recurrent uveitis which sometimes develop to glaucoma, without subjective signs. PMID- 1588758 TI - [Adult Still's disease]. AB - Still's disease was reported to be a type of Juvenile Rheumatoid Arthritis (JRA) by Still in 1897. Adult-onset Still's disease is an important clinical entity inducing fever, skin rash and polyarthritis. Spiking fever and rash are characteristic features for early diagnosis. Although chronic polyarthritis is similar to RA, ankylosis of hand joint is characteristic for Still's disease rather than destructive change. Increased ESR, negative autoantibodies, leukocytosis, liver dysfunction and hyperferritinemja are major laboratory findings. A markedly increased level of serum ferritin can be used, not only as an indicator of disease activity, but also as a diagnostic marker of the disease. For therapy, a moderate dose of steroid is the most effective. PMID- 1588759 TI - [Felty's syndrome]. AB - Felty's syndrome is a variant of rheumatoid arthritis with a triad of leukopenia, splenomegaly and typical rheumatoid arthritis, and often accompanies the other extraarticular symptoms, such as subcutaneous nodules, lymphadenopathy, anemia, thrombocytopenia, leg ulcers, fever and weight loss. In addition to the decreased number of leukocyte, impaired functions of leukocytes were also revealed. These changes were considered as the cause of repeated infections, which was the major cause of death in Felty's syndrome. Splenectomy is not fully effective for leukopenia and for the repeated infection. Glucocorticoid therapy can increase leukocyte count, at least tentatively. It has been reported that gold was effective for leukopenia, repeated infection and skin ulcer. However, the definitive way of treatment of this syndrome based on the pathogenesis of this syndrome, remains to be established. PMID- 1588760 TI - [Overlapping syndrome]. AB - Overlapping syndrome (OS) is usually used as the term of the combinations of three connective tissue diseases, i.e., systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS) and polymyositis (PM) or dermatomyositis (DM). OS is sometimes confused with mixed connective tissue disease (MCTD) since the definitions of the both diseases have not been established yet. Rheumatoid arthritis (RA) is a distinct disease and only exceptionally associated with the other CTD. These rare cases include destructive arthritis of SLE and PSS, multiple peripheral type of psoriatic arthritis, and arthritis associated with X linked hypogammaglobulinemia and selective IgA deficiency. The conditions complicated with RA are not uncommon. They are osteoporosis, Sjogren's syndrome, amyloidosis and so on. There are some rare conditions or diseases which will be able to develop to RA. These peculiar cases include juvenile rheumatoid arthritis, adult onset Still's disease, polymyalgia rheumatica and palindromic rheumatism. PMID- 1588761 TI - [Epidemiology, prognosis and causes of death in rheumatoid arthritis]. AB - The prevalence of RA in Japan has been reported to be approximately 0.3% of general population and the ratio of male to female patients is 1 to 4. The course of RA is classified into 3 types, those are monocyclic, polycyclic and progressive. The polycyclic and progressive courses of RA would have been ameliorated by the recent progress of medical and surgical treatment and an increased number of patients in monocyclic course would be expected. The mortality rate among RA patients is higher than that of population control. There are causes of death directly related to rheumatoid process itself and resulted from drug treatment. The former includes secondary amyloidosis and basilar impression and the latter includes infection, renal failure and GI bleeding. PMID- 1588762 TI - [Progress in clinical electrophysiologic study (EPS): recent tendency]. AB - About twenty years have passed since the clinical introduction of electrophysiologic study (EPS). The mechanism of arrhythmias can be understood by EPS, and EPS-guided therapy is available theoretically. Of course, not all arrhythmia needs EPS, because other non-invasive tests are available. Clinically, reentry is the most frequently observed mechanism. Therefore, EPS is most suitable for the reentrant arrhythmias which can be repeatedly initiated and terminated by programmed stimulation. In many tachyarrhythmias, slow conduction pathway or area essential for reentry are demonstrated. On the other hand, triggered activity and abnormal automatism have been less frequently observed clinically. Today, application of EPS has been extended to catheter ablation for which precise mapping is required. PMID- 1588763 TI - [Growth retardation in children with frequent relapsing nephrotic syndrome on steroid--improvement of height velocity after administration of immunosuppressive agent]. AB - In a study involving 22 cases of nephrotic syndrome in children, investigations were made of growth disturbance caused by corticosteroid in relation to dose of the steroid and age levels at steroid treatment and also of the effects of concomitantly used immunosuppressive drugs. The final height of frequent relapsing nephrotic syndrome was below M-2SD in approximately 30% of cases. Final heights of boys receiving the steroid from 12 to 16 years of age and of girls treated with the steroid from 10 to 14 years of age were below M-2SD and 10 cm lower than the target height. Final heights of boys and girls who could be withdrawn from steroid therapy by the age of 14 and 12, respectively, were invariably within or above the normal range. The addition of azathioprine therapy resulted in no appreciable reduction of steroid dosage nor improvement of yearly growth rate, although the frequency of relapse for that year was diminished. Under a regimen of concomitant cyclophosphamide the frequency of relapse and steroid dosage was also reduced but the growth rate was accelerated, no significant reduction of steroid consumption was achieved. The administration of cyclosporin A in doses of 1.5-5.0 mg/kg was marked by a reduction in steroid dosage as well as in the frequency of relapse and allowed for near normal growth rate, with no significant differences being observed between the high dose group (3-5 mg/kg/day) and the low dose group (1.5-2.5 mg/kg/day). Prolonged steroid therapy in frequent relapsing nephrotic syndrome may produce dwarfism and other distressing side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588764 TI - [A study on microproteinuria among diabetic and obese subjects without clinically overt proteinuria]. AB - In metabolic disorders such as diabetes mellitus (DM) and obesity, renal abnormalities may also occur even when renal dysfunction is not be detected by conventional urinalysis. By use of immunological technique, an investigation was made on the subclinical abnormality in the excretion of urinary proteins in DM and obese (OB) subjects. Urinary excretion of the proteins (albumin, IgG, IgG4, beta 2-microglobulin) and fractional clearances (clearance ratios to creatinine clearance) at sitting position were respectively measured. Albumin excretion rate (AER) and fractional albumin clearance were higher in DM and OB than normal controls (NC). In non-diabetic subjects (OB+NC), body mass index (BMI) significantly positively correlated with AER and fractional albumin clearance. In DM, not only AER and fractional albumin clearance but also IgG4 excretion rate and fractional IgG4 clearance positively correlated with BMI. In DM with BMI less than 22 Kg/m2, HbA1C significantly correlated with AER, IgG4 excretion rate, and fractional albumin and IgG4 clearances. The data suggest that microproteinuria in DM and OB may be of glomerular origin. In DM, in the light of an increase in urinary excretion of negatively charged IgG4, it is also suggested that proteinuria is attributed to the alteration of charge barrier as well as to that of glomerular hemodynamics. Lastly but not least , obesity-related factor should also be taken into account in the development of microalbuminuria of the diabetic patient. PMID- 1588765 TI - [Antihypertensive effect of a non-peptide angiotensin II receptor antagonist, MK954, in patients with essential hypertension]. AB - We examined the chronic effects of MK954, a novel orally active angiotensin II receptor antagonist, on blood pressure and renal function in 8 patients with essential hypertension for 2-4 weeks. All patients, four men and four women, 48.0 +/- 15.3 year-old (mean +/- SD), were hospitalized and given normal sodium diet (NaCl 10 g/day). After a control period with placebo for one week, MK954 was administered orally at 8 AM every day. The initial dose of MK954 was 12.5 mg/day, then the dose was increased up to 100 mg/day until diastolic blood pressure fell below 90 mmHg. The average dose was 59.4 +/- 43.7 mg/day. Casual blood pressure in supine position decreased significantly from 161.0 +/- 6.6/95.0 +/- 3.5 mmHg to 145.8 +/- 8.1/83.3 +/- 3.7 mmHg without any change in pulse rate. Non-invasive ambulatory blood pressure monitoring revealed that once daily administration of MK954 lowered blood pressure for 24 hours but did not affect circadian rhythm or variability of blood pressure. Reduction of blood pressure was slightly greater during day time than during sleeping time. Unlike a peptide angiotensin II antagonist, there was no pressor action of MK954 as agonist. No significant alternations were observed in body weight, serum electrolytes, creatinine clearance, urine volume or urinary excretion of sodium. Plasma renin activity (PRA) rised significantly after MK954 treatment but plasma aldosterone concentration (PAC) did not change. The reasons why PAC was not reduced are unclear. The doses of MK954 employed in this study might be insufficient to inhibit adrenal angiotensin II receptor. In conclusion, MK954 has long acting hypotensive effect in essential hypertension without affecting renal function. PMID- 1588766 TI - [Protective effect by piperacillin against renal impairment caused by amikacin]. AB - This study is aimed to demonstrate that renal impairment caused by administration of amikacin (AMK) alone can be lessened by co-administration of piperacillin (PIPC). The patients in the present study were divided into three groups. In "group P" and "group A", PIPC alone and AMK alone were administered, respectively. In "group P+A", PIPC and AMK were co-administered. Dosage of AMK was individualized based upon the therapeutic drug monitoring method, and that of PIPC was adjusted depending upon the creatinine clearance of a patient. In group A, urinary concentrations of beta 2-microglobulin and lysozyme, and urinary excretion of beta 2-microglobulin, lysozyme and gamma-GTP per day were significantly higher (p less than 0.05) than those in group P. These differences were not observed, however, between group P and group P+A. The trough value of AMK, 11 days after AMK administration, was significantly higher in group A (p less than 0.05) than that in group P+A. Incidence of renal impairment, as judged from urinary excretion of beta 2-microglobulin per day and urinary lysozyme concentration, was significantly higher in group A (p less than 0.05) than that in group P+A. These findings indicate that co-administration of PIPC with AMK can lessen the renal impairment caused by administration of AMK alone. PMID- 1588767 TI - [Methylguanidine kinetics during oral active vitamin D pulse therapy for secondary hyperparathyroidism]. AB - Active vitamin D (VD) metabolite preparations have been used in the management of secondary hyperparathyroidism (2 degrees HPT) due to impaired calcium and phosphorus metabolism and can allegedly be expected to prevent, to some extent, the progression of this pathological condition. Unfortunately, however, it is not uncommon for us in routine clinical practice to find 2 degrees HPT of moderate or greater severity embarrassingly unamenable to treatment with these VD preparations in ordinary oral therapeutic doses. Recent studies have gradually reported that intravenous administration of 1,25-(OH)2D3 and oral active VD pulse therapy has been therapeutic approach to 2 degrees HPT. Methylguanidine (MG) among other GCs, its precursor is already identified as creatinine and activated oxygen as well PTH and VD are known to participate in the process leading to its formation. In the present study, we administered oral 1,25-(OH)2D3 pulse therapy to patients with chronic renal failure for the treatment of 2 degrees HPT in an attempt to assess the effectiveness of this therapeutic regimen and to explore the clinical effect of MG on responsiveness to the therapy. The purpose of this paper is to present the results thus obtained. Oral 1,25-(OH)2D3 pulse therapy (6 micrograms once a week) was administered to 21 hemodialysis patients with for 12 weeks. Of these 21, 10 patients responded to the therapy with a more than 20% reduction in serum (PTH): (responsive group), whereas the remaining 11 did not (resistant group). Pretreatment serum PTH levels were significantly higher in the latter group than the former.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588768 TI - [Is there any correlation between urea kinetics and the clinical outcomes in CAPD patients?]. AB - Urea kinetic modeling was applied to 19 CAPD patients followed in our outpatient clinics. Serum beta 2-microglobulin was also measured as a marker of large molecular weight substances. Clinical conditions of patients were assessed by both doctors and patients. Patient's assessment were done by the questionnaire. Indices of urea kinetics (KT/V, PCR) and biochemical parameters were compared between well-treated and not well-treated patients judging from patient's and doctor's assessment scores. The rate of peritonitis was significantly higher in the latter group. None of the parameters were different between 2 groups except for serum albumin. There was a significant correlation between serum concentration of albumin and doctor's assessment score (gamma = 0.52). In conclusion, urea kinetic parameters is not a good indicator for adequacy of dialysis in our CAPD population. Serum albumin seems to be one of the indices for adequate dialysis. However, clinical symptoms and signs are more valuable than biochemical parameters for the assessment of adequacy of dialysis. PMID- 1588769 TI - [Survival of bacteria, and release of the endotoxin from the bacterial cells in the dialysates]. AB - Survival of bacteria and release of the endotoxin from the bacteria with and without ultraviolet irradiation in three kinds of dialysate were investigated. The results obtained are as follows: (1) No growth of S. aureus, E. coli, P. aeruginosa, Aspergillus and C. albicans in the saturated dialysates tested were observed. (2) All of the bacterial cells tested here is gradually, and naturally spontaneously inactivated in all the dialysates. (3) Among the dialysates tested, the saturated dialysate, AF-2, is the most effective for inactivating P. aeruginosa ATCC, but the effect depends upon the isolates of P. aeruginosa. (4) The inactivating effect was somewhat decreased when the saturated AF-2 solution was diluted, but the killing effect was still maintained. (5) The bacterial cells are constantly and significantly inactivated by UV irradiation, especially by the direct irradiation. The indirect irradiation, i.e., through glass, has remarkably less effective than the direct one. However, a tendency of the decrease of bacterial cells by the indirect irradiation is maintained with the killing effect of the dialysated, especially in the case of AF-2 solution. (6) No significant increase of endotoxin was observed, even when the bacterial cells were killed by UV irradiation. Therefore, it is recommended to use UV irradiation for inactivating the bacteria. From the results obtained here, it is indicated that there is no possibility of the growth of naturally contaminated bacteria in the dialysates, and is an effectiveness of the use of UV irradiation for inactivating the bacteria cells, in terms of release of the endotoxin from the dead cells. PMID- 1588770 TI - [Changes of urinary human epidermal growth factor excretion in 16 patients with acute renal failure]. AB - In order to evaluate the clinical significance of urinary human epidermal growth factor (hEGF) in patients with acute renal failure (ARF), urinary hEGF levels were determined by radioimmunoassay, and were corrected for creatinine (creat.) concentrations in 16 patients with ARF and 12 healthy controls. The urinary hEGF levels significantly decreased in patients with ARF in acute phase compared with normal control subjects (0.98 +/- 0.20 vs 13.74 +/- 1.18 ng/mg creat. p less than 0.01), and it subsequently increased during recovery phase (6.10 +/- 0.73 ng/mg creat. p less than 0.01 vs acute phase). A significant correlation between the urinary hEGF levels and creatinine clearance (r = 0.712, p less than 0.001) and an inverse correlation between urinary hEGF levels and fractional excretion of sodium (r = -0.406, p less than 0.05) was demonstrated. The remarkable decrease of urinary hEGF excretion preceded the increase of urinary beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase levels. Our data suggests that urinary hEGF originates from renal tissues in humans and measurement of urinary hEGF is useful for diagnosing renal damage and recovery of renal tissues from severe tubular injury. PMID- 1588772 TI - [Intrarenal arterial Doppler sonography in patients with various renal disease: correlation of resistive index with biopsy findings]. AB - Duplex Doppler sonography (ultrasonic equipment: Toshiba SSA-270A) were performed in the patients with various renal disease (male 44, female 32) admitted to our hospital between June 1990 and August 1991. Interlobar arterial blood flow velocity was measured at the side of renal pyramid through a longitudinal scan. Both the maximum blood flow velocity (Vmax) and the minimum blood flow velocity (Vmin) were measured quantitatively and resistive index (RI: defined as (Vmax Vmin)/Vmax) were calculated. Vmax and Vmin correlated well with the creatinine clearance (Ccr) (r = 0.56, r = 0.66 respectively), whereas RI, by which we can detect Doppler waveform changes, correlated weak with Ccr (r = 0.39). We found twenty-nine patients (40%) with an elevated RI (greater than or equal to 0.70). They had severe renal dysfunction and active pathologic findings in the tubulo interstitial or vascular compartment of the kidney. Doppler examination of renal blood flow velocity was valuable not only to estimate renal function but also to assess pathophysiology of renal disease. PMID- 1588771 TI - [Antihypertensive effects and pharmacokinetics of NZ-105 single administration in patients with hypertension]. AB - The influence of renal function on the antihypertensive effect and pharmacokinetics of NZ-105 were studied in 7 patients with essential hypertension (EH) and 6 patients with hypertension having impaired renal function (RH). 1. As for the hypertensive effect, both in EH and RH, the maximum antihypertensive effect was attained 3 to 5 hr after drug administration and there was not significant difference between EH and RH. 2. There was not significant difference in transition of plasma concentration of NZ-105 between EH and RH. 3. Concerning pharmacokinetic parameters of NZ-105, there was significant difference between EH and RH in Tmax. at 20 mg of NZ-105 administration. However, in regard to Tmax. at 30 mg of NZ-105 administration and Cmax., AUC and t1/2 at 20 mg, 30 mg of NZ-105 administration, there were not significant differences between EH and RH. 4. There was no correlation between t1/2 and serum creatinine levels. 5. All cases showed good tolerance without any adverse effect. PMID- 1588773 TI - [A case of granulomatous interstitial nephritis presented reversible renal failure treated with the steroid therapy: repeated renal biopsy case]. AB - This report describes clinical and histopathological findings of a case of a 43 year-old male with granulomatous interstitial nephritis. The patient developed renal failure following renal insufficiency of 4 months duration. The patient presented with lethargy and nocturia. The first renal biopsy revealed granulomatous interstitial nephritis. There was no apparent evidence of a systemic granulomatous disease or drug hypersensitivity. Therapy with reducing regime of prednisolone produced a marked improvement in symptoms and renal function. Relapse occurred 3 months later in association with early discontinuation of the corticosteroid therapy. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in both kidneys. The second renal biopsy did not show the obvious improvement. With the re-administration of the corticosteroid therapy, renal function rapidly improved again. Twelve months after the re administration of the steroid therapy, Ga-scintigraphy showed no renal uptake. Corticosteroid therapy yielded a favorable outcome for renal function. The third renal biopsy showed disappearance of the granulomas lesion. Re-administration of the corticosteroid therapy continued for 22 months and the patient has not yet relapsed 9 months after the withdrawal of the steroid therapy. PMID- 1588774 TI - [A case of idiopathic chronic interstitial nephritis progressed to renal failure without proteinuria nor hematuria]. AB - A case of idiopathic interstitial nephritis who underwent to chronic renal failure without history of hematuria nor proteinuria is discussed. A 46 years old woman who showed gradually elevation of serum creatinine (1.3-2.5 mg/dl) admitted on our hospital. On occasions of pregnancy, health examination or hospital visit, she has never been pointed out hematuria nor proteinuria. Immunological disorders such as SLE, metabolic diseases, urinary tract obstruction and chronic urinary tract infection were excluded by the examinations after admission. Because of the severe enzymuria (beta 2-microglobulin, N-acetyl glucosaminidase), chronic interstitial nephritis was considered, and renal biopsy was performed. Severe tubulointerstitial changes were observed histologically, however, glomerular damage was comparatively mild. From these results, she was diagnosed idiopathic chronic tubulointerstitial nephritis. In this case, hematuria and proteinuria were absent until severe renal dysfunction. This may be caused by that inflammation was located to the tubulointerstitial area. The observation of enzymuria seemed to be important to diagnosis and follow-up of the interstitial nephritis. PMID- 1588775 TI - Method for in-shoe shear stress measurement. AB - A methodology is described for use of a shear transducer, based on a magneto resistive principle, to measure stresses under the plantar surface of the foot in shoe during walking. Particular attention is paid to a projected application for study of diabetic plantar ulceration and its management by footwear. The transducer has a disc construction, approximately 4 mm thick by 16 mm diameter, and measures two orthogonal axes of shear simultaneously; this disc is mounted into an inlay that can be inserted into any stock orthopaedic shoe of the type commonly prescribed for diabetic foot problems. The transducer is located in the metatarsal head region of the inlay; exact placement of the transducer is determined by reference to the direct pressure distribution, the common method of palpation shown to be imprecise. Pilot trials on normal subjects are presented to evaluate the method. PMID- 1588776 TI - Development of an above-knee prosthesis equipped with a microcomputer-controlled knee joint: first test results. AB - The shortcomings of conventional above-knee prostheses are due to their lack of adaptive control. Implementation of a microcomputer controlling the knee joint in a passive way has been suggested to enhance the patient's gait comfort, safety and cosmesis. This approach was used in the design of a new prosthetic system for the above-knee amputee, and tested on one patient. The knee joint of a conventional, modular prosthesis was replaced by a knee joint mechanism, equipped with a controllable brake on the knee joint axis. Sensors and a microcomputer were added, keeping the system self-contained. The modularity of the design permits the use of an alternative, external, PC-based control unit, emulating the self-contained one, and offering extended data monitoring and storage facilities. For both units an operating environment was written, including sensor/actuator interfacing and the implementation of a real-time interrupt, executing the control algorithm. A double finite state approach was used in the design of the control algorithm. On a higher level, the mode identification algorithm reveals the patient's intent. Within a specific mode (lower level), the relevant mode control algorithm looks for the current phase within the gait cycle. Within a particular phase, a specific simple control action with the brake replaces normal knee muscle activity. Tests were carried out with one prosthetic patient using a basic control algorithm for level walking, allowing controlled knee flexion during stance phase. The technical feasibility of such a concept is illustrated by the test results, even though only flexion during early stance phase was controlled during the trials.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588777 TI - Application of the finite-element method to simulation of damage to the human skull as a consequence of missile impact on a multi-layered composite crash helmet. AB - Finite-element analysis is a powerful technique which could be applicable to the study of a wide range of circumstances where the frame and/or the vital organs of the body are subjected to extreme loading conditions. This paper reports the results of an exploratory investigation in which the performance of a crash helmet in protecting the skull from an impacting load is modelled. The immediate objective is to show how a typical crash helmet design of glass-reinforced plastic (GRP) outer casing with quasi-foam-like liner can, with a suitable choice of material properties, attenuate the transfer of energy from the impacting mass such that the damage intensity to the skull is minimized. A simplified structure for both helmet and skull shape is adopted and the skull is modelled as being supported on an elastic foundation. The material properties used are representative rather than being accurately matched to experimentally determined ones. Several aspects of the modelling technique are worthy of particular note: the simulation of material anisotropy by means of multiple reinforcement layers with varying orientation, the use of dashpot elements for energy attenuation and the incorporation of multipoint constraint between the skull and the helmet lining to ensure integrity of the model with correct stiffness matrix values and allowing independent monitoring of all stress levels at the mating interface region. The results of the modelling show that the specific limited objectives can be met but also indicate how vitally important information could be obtained from similar but more detailed studies which included representative modelling of the body organs and skeleton. PMID- 1588778 TI - Prediction of bone adaptation in the ulnar-osteotomized sheep's forelimb using an anatomical finite element model. AB - A method for the prediction of the time-course of bone adaptation based on an alternative hypothesis of strength optimization has been previously investigated and developed by Prendergast and Taylor. This paper extends our work in the study of the effectiveness of this bone adaptation model in predicting similar bone remodelling to that observed in animal experiments. In particular the experimental work which has been modelled is that of Lanyon, Goodship, Pye and McFie. An anatomical finite element model of the sheep's forelimb has been generated for this purpose and is used to estimate stresses in the bone structure for the normal and osteotomized condition. The propensity for remodelling of the altered bone structure is predicted using the proposed remodelling law for the new stress field in the bone structure. The preliminary results indicate an initial bone adaptation pattern similar to that observed experimentally without the necessity to use arbitrarily different constants for the endosteal and periosteal surfaces. We therefore suggest that the remodelling law based on damage and repair gives a better predictive model of bone adaptation than previous models. PMID- 1588779 TI - Finite-element analysis in cartilage biomechanics. AB - Articular cartilage is a complex composite material in engineering terms. It is inhomogeneous, anisotropic and demonstrates a time-dependent nonlinear relationship between stress and strain. This paper reviews the application of the finite-element method to the loading of articular cartilage, and highlights the potential of this numerical technique in the investigation of osteoarthritis. PMID- 1588780 TI - Shape analysis for classification of malignant melanoma. AB - Melanoma is a malignant skin tumour. If detected and surgically removed early whilst residing in the superficial part of the skin the prognosis is excellent. A seven-point check-list of signs and symptoms has been adopted by the Cancer Research Campaign to help non-dermatologists distinguish benign pigmented lesions from melanoma. The presence of irregularity in shape or outline of a mole is one of these important signs. However, it has recently been shown that not only patients, but also clinicians have difficulty in agreeing upon whether a mole exhibits irregularity or not. Computer image analysis methods have been developed to derive quantitative measures of those shape parameters which dermatologists appear to use in their assessment of shape irregularity. The overall shape of the lesion is expressed by the 'bulkiness' measure. Irregularity of the border is expressed by two fractal dimension measures, one for the 'structural' aspect of the shape and the other for the 'textural' aspect. These measures were used in combination to classify melanomas in the study containing silhouettes of 43 melanomas and 45 benign lesions producing correct classification with 91% sensitivity and 69% specificity. This paper describes computer image analysis aspects of the study. PMID- 1588781 TI - A physiological model of glucose-insulin interaction in type 1 diabetes mellitus. AB - A clinical model of glucose-insulin interaction in insulin-dependent diabetes mellitus has been developed for patient and medical staff education. The model attempts to reflect the underlying (patho)physiology of insulin action and carbohydrate absorption in quantitative terms such as insulin sensitivity, volume of glucose and insulin distribution and maximal rate of gastric emptying. The model's predictions also allow a 24 h simulation of patient blood glucose profiles to be generated. A description of the model is provided and its operation illustrated by clinical case studies of insulin-treated diabetic patients. The possible use of the model as a tool for automated insulin dosage adjustment is explored. PMID- 1588782 TI - Insulin dosage adjustment in diabetes. AB - A prototype computer system has been developed to provide advice on the day-to day adjustment of carbohydrate intake and insulin regimen in the insulin-treated diabetic patient. The system also produces a 24-hour simulation of the patient's blood glucose profile based on these adjustments. Advice is generated by a qualitative knowledge-based system which suggests what the next step in improving glycaemic control might be for a given patient, e.g. 'decrease evening medium acting insulin by two units'. Simulations are provided by a non-linear model which consists of a one-compartment glucose model linked to a model with plasma and 'active' insulin compartments. A description of the integrated system is provided and its operation illustrated by clinical case studies from insulin treated diabetic patients. PMID- 1588783 TI - Non-invasive Doppler ultrasound technique for the in vivo assessment of aortic compliance. AB - A non-invasive Doppler ultrasound technique for the assessment of aortic compliance is described. This is based on the in vivo measurement of pulse wave velocity along the thoraco-abdominal aortic pathway. A structured protocol has been developed to improve the reproducibility of the technique as well as for the purposes of operator training. Preliminary results of a study of both the intra- and inter-observer variability of the method are provided and problems associated with the technique are discussed. Medical disorders such as atherosclerosis, diabetes mellitus and familial hypercholesterolaemia have all been shown to affect arterial wall compliance. We suggest that the measurement of aortic compliance in vivo may be a useful, non-invasive tool for assessing these patients' susceptibility to atheromatous arterial disease and for monitoring their response to therapy. PMID- 1588784 TI - Computer simulation of the effects of ventricular interdependence on indices of left ventricular systolic function. AB - The influence of ventricular interdependence on cardiovascular function has been convincingly demonstrated. In the intact cardiovascular system ventricular interdependence is always present, and thus measures of cardiac function include the contribution of ventricular interdependence (VI). A cardiovascular system model is presented and used to discuss how VI affects selected indices of left ventricular (LV) systolic function. Indices of LV function studied were the ejection fraction, stroke work, peak time derivative of ventricular pressure (dP/dT) and the LV end-systolic pressure-volume relationship. The effects of right ventricular (RV) volume through systolic VI on these indices are conveniently studied by comparing the model responses to pulmonary artery (PA) and vena caval (VC) occlusions; both PA and VC occlusion reduce LV volume, but the RV volume is increased by PA but reduced by VC occlusions. Through systolic VI the increase in RV volume with PA occlusion shifted the LV end-systolic pressure-volume relationship to the left and thus affected measures of LV maximum elastance. The LV ejection fraction, peak dP/dT and stroke work were all augmented by the increase in RV volume associated with the PA occlusion. Experimental studies comparing the responses to PA and VC occlusions are in broad agreement with the results described here. Systolic VI also shifted the cardiac function curve, a global measure of cardiac function, to the left. The results thus suggest that commonly used indices of LV systolic function are dependent on RV function and do not solely reflect LV function. PMID- 1588785 TI - A new technique for the identification of respiratory sinus arrhythmia in utero. AB - Fetal heart rate (FHR) monitoring forms the basis of routine fetal assessment, particularly short-term variability in the interbeat interval which can be difficult to interpret. Respiratory sinus arrhythmia (RSA), the change in heart rate in response to breathing, contributes to short-term variability, and the presence of RSA in utero may reflect the functional integrity of the central nervous system. This paper describes the use of Doppler ultrasound to derive the required measures of fetal heart rate and fetal breathing movements and spectral analysis to identify RSA. Cases are presented to illustrate the results obtained both in the presence and absence of RSA. PMID- 1588786 TI - Wavelet transform as a potential tool for ECG analysis and compression. AB - The recently introduced wavelet transform is a member of the class of time frequency representations which include the Gabor short-time Fourier transform and Wigner-Ville distribution. Such techniques are of significance because of their ability to display the spectral content of a signal as time elapses. The value of the wavelet transform as a signal analysis tool has been demonstrated by its successful application to the study of turbulence and processing of speech and music. Since, in common with these subjects, both the time and frequency content of physiological signals are often of interest (the ECG being an obvious example), the wavelet transform represents a particularly relevant means of analysis. Following a brief introduction to the wavelet transform and its implementation, this paper describes a preliminary investigation into its application to the study of both ECG and heart rate variability data. In addition, the wavelet transform can be used to perform multiresolution signal decomposition. Since this process can be considered as a sub-band coding technique, it offers the opportunity for data compression, which can be implemented using efficient pyramidal algorithms. Results of the compression and reconstruction of ECG data are given which suggest that the wavelet transform is well suited to this task. PMID- 1588787 TI - Immunogenotypes and clonal culture analysis in B-precursor acute lymphoblastic leukemia. AB - Immunogenotypic changes in 32 patients with B-precursor acute lymphoblastic leukemia (ALL), including three patients with t(4;11) and 13 with t(9;22), were determined using immunoglobulin heavy (IgH) chain gene probe and T-cell receptor beta, gamma and delta chain gene probes. Clonogenic assay was performed in 12 of the 32 patients. In this study, four patients had a germline configuration of the IgH chain gene, showing a dissociation between phenotypic and genotypic expression; three patients had Philadelphia-positive (Ph+) ALL. The immunogenotypic manifestation in Ph+ ALL does not depend on whether the leukemia cells had rearrangement within the major breakpoint cluster region (major-BCR) DNA sequence or the leukemia cells had myeloid-associated antigens. Colony assay using various recombinant cytokines demonstrated that the leukemia cells from four of 12 patients formed colonies in response to myelopoietic stimulants; three of the four patients were major-BCR-rearranged Ph+ ALL. Notably, cells from one patient with Ph+ ALL formed colonies on the addition of granulocytic colony stimulating factor. This indicates not only the biological heterogeneity of ALL cells but also that some of the characteristics of the cells are related to specific chromosome changes. PMID- 1588789 TI - Adhesion molecules VLA-1 to VLA-6 define discrete stages of peripheral B lymphocyte development and characterize different types of B cell neoplasia. AB - VLA-1 to VLA-6 are cell-surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. In addition, VLA-4 binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion prerogative for lymphocyte extravasation or 'homing'. Using frozen tissue of normal lymphoid organs and of 100 morphologically and immunologically typed B cell neoplasias, monoclonal antibodies to all six VAL-alpha and to the common beta-chain were applied to serial sections. VLAs were found differentially expressed in cytologically and microtopographically defined B-cell subsets [follicular mantle zone cells (MZ), follicular center cells (FC), extrafollicular cells (EF), and plasma cells (PC)] of normal spleen, lymph node, and thymic medulla (which contains an EF compartment). Thus, these cell types, which correspond to discrete stages of B cell development, can also be defined by their VLA status. Acute B lymphoblastic leukemia (ALL) was VLA-1-, 2-, 3 +/-, 4 +/-, 5 +/-, 6-. The VLA-1-, -2 +/-, 3+, 4+, -5+, -6-phenotype of chronic B lymphocytic leukemia (CLL) resembled that of MZ. Hairy cell leukemia (HCL) differed from CLL in its tendency to lack VLA-2, in its consistent lack of VLA-3, and altogether resembled splenic EF in its VLA profile. Mantle zone lymphoma (MZL) consistently expressed VLA-3 and -4 and frequently VLA-5. Nodal follicular center cell lymphomas (FCCL) were VLA-1- and 2- and very rarely expressed VLA-5 and -6. Thus, FCCL although roughly corresponding to FC, tended to aberrantly express VLA-3 and/or VLA-4. Burkitt's lymphoma resembled FCCL but expressed VLA-4 more frequently and at higher levels. Mediastinal clear cell lymphoma of B-cell type differed from FCCL in its regular lack of VLA-3, -5, and -6 and in frequently lacking VLA-4. Medullary plasmacytoma was VLA-1-, -2-, -3 +/-, -4 +/-, -5-, -6+, thus being the only B cell neoplasia which was consistently VLA-6+. With respect to the well-known clinical characteristics of the B cell malignancies examined, the leukemic phenotype might crucially depend on the presence of VLA-5. PMID- 1588788 TI - Mutations of the p53 gene in B-cell chronic lymphocytic leukemia: a report on 39 cases with cytogenetic analysis. AB - Mutations of exons 5 to 8 of the p53 gene were looked for in 39 cases of B-cell chronic lymphocytic leukemia (CLL) using polymerase chain reaction single-strand conformation polymorphism analysis and DNA sequencing. All patients also had cytogenetic analysis. A point mutation, leading to an amino acid change in the p53 protein was found in four cases, involving exon 7 (one case) or exon 8 (three cases). Mutations seemed to predominate in advanced clinical stages (Binet's stage C). All four patients with 17p monosomy had a mutation whereas no mutation was found in the 35 patients with cytogenetically normal 17p. These findings suggest that p53 mutations are relatively rare in B-cell CLL, and largely predominate or may even be restricted to patients with 17p monosomy (who constitute about 5% of all B-cell CLL patients in large published series). In those patients, the mutations may play a role in leukemogenesis through loss of tumor suppressive activity of normal p53 genes. PMID- 1588790 TI - Unique lymphoid cell subset target to infection and proliferation induced in vitro by a murine leukemia virus. AB - The mechanisms by which non-oncogene bearing, slowly transforming T-cell-tropic retroviruses induce leukemia is not well understood. Viruses such as the murine radiation leukemia virus (RadLV) induce oncogenic transformation of T-cells in the thymus only in vivo and after a long latency. The capacity of RadLV to induce proliferation of lymphoid cells in vitro has been analysed here as a first attempt at mapping oncogenic transformation. Autonomously replicating cell lines have been isolated following exposure of splenic lymphocytes to two different isolates of RadLV, following in vitro culture in the presence of T-cell growth factors. Cells of similar precursor lymphoid morphology and phenotype have been isolated and cloned from cultures established from different animals. These cell lines all grow independently of exogenous growth factors in vitro, but are not tumorigenic in mice. Exposure to RadLV under the culture conditions provided has allowed integration of a new retroviral genome into each cell line, but no active replication of virus has been detected in any of the cell lines analysed. A common cell type resembling a lymphoid precursor has been induced to proliferate. These cell lines express cell surface markers attesting to their bone marrow origin, such as CD44 (Pgp-1), Gr-1, B220 and NK1.1, but they do not show the characteristics of T cells which have undergone differentiation within the thymus. They do not express the Thy-1 marker, nor show rearrangement involving any of the T-cell receptor (TCR) alpha, beta gamma or sigma genes. These cells bind several antibodies specific for the CD3-epsilon and TCR-alpha beta structures, and there appears to be aberrant expression of TCR proteins in cells bearing fully rearranged TCR genes. Precursor lymphoid cells and not mature T cells in spleen, appear to be appropriate targets for RadLV-induced proliferation/immortalisation in vitro. Oncogenic transformation induced by RadLV in vivo may occur within precursor lymphoid cells and must be a complex process dependent on both the differentiation events which occur within the thymus, as well as the thymic environment of stromal cells. PMID- 1588791 TI - Detection of clonality in childhood B-lineage acute lymphoblastic leukaemia by the polymerase chain reaction. AB - The polymerase chain reaction (PCR) was used to study clonality in a group of children with B-lineage acute lymphoblastic leukaemia (ALL). Rearrangement of the immunoglobulin heavy chain gene (IgH) results in a hypervariable sequence known as the complementarity determining region III. This can be amplified by the PCR using one pair of consensus primers. The PCR product is highly clone-specific in both size and sequence. Successful amplification was achieved in 50 of 62 cases of B-lineage ALL studied (81%). Both DNA and RNA gave almost identical results. In contrast amplification was only achieved in 2 of 42 control cases (non-B lineage leukaemias, normal and reactive marrows); these were both cases of T-ALL with IgH rearrangement on Southern blotting. The main advantages of this technique over Southern blot assessment of clonality are the short time to result and requirement for much less DNA allowing study of small samples eg cerebrospinal fluid and testicular biopsies. It is also generally more sensitive for the detection of a malignant clone in a polyclonal marrow cell population and forms the basis of techniques to study minimal residual disease (MRD). PMID- 1588792 TI - Phorbol myristate acetate-induced expression of high-affinity interleukin 2 receptors and production of interleukin 2 by human acute lymphoblastic leukemia T cells. AB - The effect of phorbol myristate acetate (PMA) on the expression of interleukin 2 receptors (IL-2R), production of IL-2 and IL-2-dependent proliferation of acute lymphoblastic leukemia T cells (T-ALL cells) from 10 patients was studied. First, the effect of PMA on the expression of cell surface markers was assessed: a decrease of CD3 and CD4, and an enhanced expression of CD8 molecule were observed on T-ALL cells. Moreover, PMA exhibited an heterogenous effect on various activation-associated molecules such as a decreased expression of transferrin receptor and T10 molecule and an induced expression of 4F2 and CD9 molecules. It is known that functional high-affinity IL-2R are composed of at least two IL2 binding molecules, the alpha (p55) and beta (p70) chains. We found that PMA induced the expression of both IL-2R alpha and IL-2R beta chains, as well as IL-2 production by T-ALL cells. These effects were time- and dose-dependent. Cross linking experiments with 125I-labelled recombinant IL-2 (125I-rIL-2) revealed both p55 (IL-R alpha) and p70 (IL-2R beta) IL-2-binding polypeptides, whereas binding equilibrium assays on PMA-treated cells demonstrated the presence of a low number (31-413) of high-affinity binding sites/cell in five out of six cases analysed, as well as intermediate affinity IL-2R (1234-3919 sites/cell) in four out of six cases, according to the time of incubation with PMA. In two cases tested high-affinity IL-2R on PMA-treated T-ALL cells could internalize 125I-rIL 2 at 37 degrees C. PMA alone enhanced the spontaneous proliferation of T-ALL cells in three cases, whereas a clear synergy between IL-2 and PMA could be detected in three patients' cells. Moreover, exogenous rIL-2 enhanced cell proliferation of PMA-preincubated T-ALL cells in four cases studied. Taken together, these observations indicate that a short-term incubation of T-ALL cells with PMA can activate the IL-2/IL-2R system on these cells without inducing strong modifications of their differentiation status. These results thus suggest that this system may be involved in the proliferation process of some activated immature T cells. PMID- 1588793 TI - Increase in interleukin 6 (IL-6) and IL-6 receptor expression in a human multiple myeloma cell line, U-266, during long-term in vitro culture and the development of a possible autocrine IL-6 loop. AB - A human multiple myeloma (MM) cell line, U-266, has developed the ability to grow independently of exogenous interleukin 6 (IL-6) during long-term cultivation in vitro. The early passage, feeder-cell dependent U-266 cell line (U-266-1970) was compared with the late passage U-266-1984 cell line with respect to response to IL-6, IL-1 beta and tumour necrosis factor alpha and expression of IL-6 and IL-6 receptor (IL-6R) mRNA and protein. The results showed that; (a) only the U-266 1970 cell line was stimulated to growth by IL-6, (b) IL-6 and IL-6R mRNA were expressed in both cell lines, (c) the level of IL-6 mRNA was increased in the U 266-1984 cell line and only this line produced IL-6 and, (d) the level of IL-6R mRNA was highest in the U-266-1984 cell line and the number of IL-6R about ten times higher than in U-266-1970. The growth of the IL-6-producing U-266-1984 cell line was inhibited by 30% by anti-IL-6R antibodies suggesting the possibility that an autocrine IL-6 loop might have developed during the long-term cultivation. In addition to many other phenotypic alterations of the U-266 cell line, having developed as a consequence of tumor progression in vitro, its growth factor requirement seems to have evolved from a dependence on IL-6 as a paracrine growth factor to a capacity for autonomous growth, dependent on autocrine IL-6 stimulation. Whether such a development also may take place in MM clones in vivo remains to be established. PMID- 1588795 TI - Ethylene glycol ethers as hemopoietic toxins--in vitro studies of acute exposure. AB - Ethylene glycol ethers and their acetate derivatives were analyzed for their toxicity in vitro on several hemopoietic cell lines, either growth-factor dependent or leukemic, in mouse, rat, and human species. Considering the concentrations that reduced the cell viability in culture by 50%, most of the ethylene glycol ethers and in particular ethylene glycol monoethyl ether (EGEE) or ethylene glycol monobutyl ether (EGBE) should be considered as hemopoietic toxins. EGBE was found to be the most potent toxin on the human promyelocytic cell line, NB4 (median inhibitory concentration (IC50) 5 mM at 6 h; IC50 0.1 mM at 96 h) but also on the factor-dependent cell line DA1 (IC50 80 microM at 48 h). Factor-dependent cell lines were not significantly more sensitive than leukemic cell lines. The toxicity of these compounds falls in the same range of concentration as benzene or phenol, but hydroquinone was significantly more toxic in the same assay (IC50 3-15 microM at 48 h). Toxic effects increased linearly with time. The toxicity of ethylene glycol ethers was confirmed by both assays for colony-forming units in culture medium (CFU-C) (human blood cord cells) and murine bone marrow long-term culture (IC50 5-10 mM). Stromal cells in the adherent layer were more resistant than hemopoietic cells. An all or none toxicity was found within a narrow range of concentration (2-5 mM for EGBE), and chronic exposure over two months did not show cumulative effects on the culture cellularity. The possibility that fibroblastic or macrophage cells worked at the detoxification of the culture is suggested. Results are discussed with regard to epidemiological and in vivo experimental data presently available. PMID- 1588794 TI - Recombinant human erythropoietin for treatment of myelodysplastic syndromes. AB - Nine patients with myelodysplastic syndromes and one patient with agnogenic myeloid metaplasia have been treated with recombinant human erythropoietin (rhEpo), at the dose of 150 U/kg/day. Although serum Epo levels were correlated with hemoglobin concentrations in the whole population of patients, they clearly appeared inadequate in some instances, if compared to those of a group of control subjects with iron deficiency anemia. Moreover, no correlation was found between serum Epo and reticulocytes. Six patients showed a partial or complete response to the treatment and the outcome was not correlated with the pre-therapy serum Epo levels; however, serum Epo was less than 100 mU/ml in three of four patients who achieved a complete response. The mechanism(s) by which Epo stimulated erythrocyte production in myelodysplastic patients is unclear, because the number of both the reticulocytes and erythroid progenitors remained unchanged during and at the conclusion of a three months' therapy. Further studies are needed to better define the optimal dosage required to correct anemia in myelodysplastic syndromes, and to clarify rhEpo mechanism of action in these diseases. PMID- 1588796 TI - Low frequency of ras oncogene mutations in Philadelphia-positive acute leukemia and report of a novel mutation H61 Leu in a single case. AB - Activating ras mutations are frequent (25-60%) in chronic myelomonocytic leukemia (CMML) and in acute myeloid leukemia (AML) (30%), in contrast to chronic myeloid leukemia (CML) in which the incidence is very low (0-3%). This might reflect that the leukemic cell in CML is at a level of differentiation in which ras gene activation is not involved or, alternatively, might be due to the presence in CML of the bcrlabl fused gene. We have analyzed the presence of point mutations in codons 12, 13, 59, 61 and 63 of N-, K-, and H-ras genes, in 26 cases of Philadelphia-chromosome-positive, bcrlabl-positive acute leukemia (Ph+ AL), and in eight CMML cases by using the polymerase chain reaction. Aberrant ras genes were detected in a single Ph+ AL case, and in four out of eight CMML patients. The Ph+ AL showing altered ras allele had an unusual point mutation in H-ras gene, substituting leucine for glutamine. This mutation has not been previously found in any hematological disease. Our findings suggest that ras mutations are probably not involved in the pathogenesis of those leukemias in which blast cells contain bcrlabl oncogene activation. PMID- 1588797 TI - Physical, phenotypic and cytochemical characterisation of stroma-adherent blast colony-forming cells. AB - Primitive cells defined as long-term culture initiating cells (LTCIC) and blast colony-forming cells (Bl-CFC) bind to cultured stromal layers, but cells at later stages of maturation [granulocyte-erythroid-macrophage-monocyte colony-forming cells (GEMM-CFC) granulocyte-macrophage (CM-CFC) and erythroid burst-forming units (BFU-E)] do not. The precise relationship between the LTCIC and Bl-CFC is not known and this study was undertaken to determine their relative positions in the haemopoietic hierarchy. We have defined the Bl-CFC population in terms of its density profile and antigenic phenotype and compared these characteristics with GM-CFC and BFU-E. The progenitor cell populations did not differ in density. The major phenotypic difference was seen using the myeloid monoclonal antibody S17-25 which reacted with fewer Bl-CFC than GM-CFC. Also, we have cytochemically analysed the cells in colonies derived from Bl-CFC. Our studies indicate that the Bl-CFC precede BFU-E and GM-CFC but not the LTCIC. PMID- 1588798 TI - Acute pulmonary failure after the first administration of recombinant human granulocyte-macrophage colony-stimulating factor. PMID- 1588799 TI - Multiple rearranged immunoglobulin genes in childhood acute lymphoblastic leukaemia of precursor B-cell origin. PMID- 1588800 TI - The effect of ontogenetic development on the anticonvulsant activity of midazolam. AB - The anticonvulsant effects and duration of protective action of midazolam against Metrazol induced seizures were studied in 528 rats aged 7,12,18,25 and 90 days. The doses of 0.025, 0.05, 0.25, 0.5 and 1.0 mg/kg were administered immediately before Metrazol (100 mg/kg in all but 18-day-old animals where 90 mg/kg were given) for detection of antimetrazol activity at all age groups. The doses of 0.05, 0.25, and/or 0.5 mg/kg were used to study the time course of the protective action of midazolam. Each experimental group consisted of eight animals. Dose dependent antimetrazol effects of midazolam till now described only in adult animals were demonstrated at all developmental stages studied. There were no qualitative differences in these effects among age groups studied. Midazolam action was better expressed against major Metrazol seizures than against minimal Metrazol seizures. Duration of the protective action depended on the dose tested at all developmental stages, as a rule, lasted longer in young animals than in adult rats. Only quantitative changes of action were found. PMID- 1588801 TI - Isolation and purification of a vascular hyperreactivity factor from rabbit kidney cortex. AB - A compound capable of amplifying the threshold pressor response to norepinephrine (NE) was obtained from rabbit kidney cortex. This compound was purified and characterized using a series of techniques including gel filtration, ion exchange chromatography, preparative electrofocusing, HPLC, FAB mass spectrometry (FAB MS), and Fourier transform infrared spectrometry. From this, an acid/heat stable (6N HC1, 160 degrees C, 24 hours), low molecular weight (ca 147) compound with a strong (+) charge density (Pi greater than 10) was identified. When injected into assay rats (i.v.), this compound amplified the pressor response to fixed doses of NE. Taken together, this compound exhibits nearly identical characteristics (i.e. acid/heat stability, structure, charge and biologic activity to the naturally occurring polyamine spermidine (SPD-145.6 daltons). Moreover, bolus injections of SPD (10 micrograms, i.v.) amplified the pressor response to NE over a range of doses from 5-25 ng. PMID- 1588802 TI - A new approach for realizing the "antioncogram". AB - On the basis of an organoid culture method which allows organoid reorganization and histotypical growth of human carcinomas under in vitro conditions, we propose in the present study an organoid culture assay (OCA) as "antioncogram", i.e., as in vitro model for testing the drug sensitivity and resistance of individual patients' carcinomas previous to clinical chemotherapy. At the beginning of the assay, specimens of human carcinomas are disaggregated to dense single cell suspensions and dropped on a filter sheet at the air-medium interface. Organoid culture nodules develop within several days to weeks. They are exposed to cytostatics by adding the drugs for 2-3 days to the growth medium below the filter sheet. At the end of the exposure period, the cytotoxic effects are estimated by determining the fraction of viable cells, measured by the uptake of neutral red in relation to the total cell mass. In the present study we could show that this assay actually reflects the different levels of experimentally induced resistance of three human carcinoma strains of an epidermoid hypopharynx carcinoma to the cytostatic drug cisplatin and is obviously suited to predict the response of individual human carcinomas to chemotherapy in a rapid and feasible manner. PMID- 1588803 TI - Up-regulation of estrogen receptors in rabbit osteoarthritic cartilage. AB - The purpose of this study was to investigate the alteration of estrogen receptors in an early stage of estradiol-induced osteoarthritic knees. After 3 weeks of intraarticular injections of estradiol benzoate to both knees in ovariectomized rabbits, the articular cartilages of femoral condyle and tibial plateau were harvested and pooled separately in each rabbit. The cytosolic estradiol receptor was determined by hydroxylapatite-column assay. The receptor levels (fmol/mg protein) were determined by the analysis of specific 3H-labelled estradiol binding data. In the present study, the specific binding to 3H-estradiol in the femoral condyle cartilage of estradiol-treated rabbits was 1.7 fold of that in vehicle-treated rabbits. The difference between them was highly significant (p less than 0.01). On the other hand, estrogen receptors were nondetectable in the tibial plateau of either vehicle- or estradiol-treated rabbits. It appeared that the cytosolic estradiol receptor existed preferentially in the cartilage of the femoral condyle, rather than in that of the tibial plateau. Since a direct link of estrogen to the development of osteoarthritis in rabbit knees was demonstrated as early as 3 weeks, it is suggested that up-regulation of estrogen receptors in cartilage might initiate the osteoarthritic changes. PMID- 1588804 TI - New method for autogenous vein grafting with the telescoping anastomotic technique. AB - An experimental study was performed to examine whether a microsurgical telescoping anastomotic technique could be applied twice in one vessel, for use in autogenous vein grafting. The rat inferior epigastric vein was grafted into a defect created in the femoral artery. The original telescoping method of Lauritzen was used, with two additional suture placements, to allow anastomosis at both proximal and distal sites. By placing the four sutures symmetrically and carefully timing the removal of the proximal and distal clamps, we achieved a patency rate of 77.3%. This is a new method for autogenous vein grafting that may serve as a prototype for an easier and possibly faster vein grafting technique. Our results appear to indicate that complete coaptation of the severed vessel ends is not necessarily required for patency in microvascular repair. PMID- 1588805 TI - Long-term histologic results of vein grafting with the telescoping anastomotic technique. AB - We studied the long-term histologic results of a new method for autogenous vein grafting to examine whether stenosis at the anastomosis is maintained over time. Nineteen rat inferior epigastric veins were grafted into the femoral artery using a telescoping sleeve technique at both the proximal and the distal anastomoses. Specimens were studied macroscopically and histologically three months later. Stenosis at the anastomosis was located near the tip of the inserted vessel. The smallest inner diameters of the proximal and distal anastomoses were about 80% of the corresponding femoral artery diameter; no statistically significant difference was found between the two anastomoses. The grafts had a thickened wall due to intimal hypertrophy and fibrosis of the media. The inner diameter of the graft was, however, about twice that of the femoral artery, and these graft changes did not create any apparent constriction within the graft. PMID- 1588806 TI - Histomorphometric study of experimental extramucosal ureteroureterostomy. AB - The reconstruction of the urinary tract is still nowadays a controversial issue. This study is based on the use of histomorphometric techniques to describe the changes which take place in extramucosal ureteroureterostomy. A medial laparotomy was performed in 41 Wistar rats. The left ureter was sectioned and an extramucosal anastomosis was performed. All rats were sacrificed 25 days postsurgery. Histomorphometric studies were performed on the sutured ureters as well as on the contralateral (unrepaired) ureters. Two of the 41 cases operated died. Five others developed hydronephrosis and/or urinary fistula. Histomorphometric studies gave an average cross-sectional area of 98,662.5 +/- 31,927 mu 2 for the anastomosed ureters versus 75,176.3 +/- 16,732.4 mu 2 for the control ureters (P less than or equal to 0.01). Sutured ureters showed an increase in the area of the muscular layer (P less than or equal to 0.001) and the submucosa (P less than or equal to 0.01) compared with control ureters. Mucosa and lumen areas showed no significant differences between the groups. Sectioned ureters show an increase in total area and width based on a hypertrophy of the muscular and submucosal layers. PMID- 1588807 TI - A scanning electron microscopic study of arterial endothelial repair under turbulent flow conditions. AB - In order to study the role of hemodynamic factors on the healing and native morphology of endothelium in vivo, turbulent arterial flow was created using a loop bypass model, with and without occlusion in the recipient vessel. In this model, several different patterns of turbulent arterial blood flow resulted. The scanning electron microscope (SEM) was used to evaluate endothelial morphology in the area of the anastomoses at 3 and 14 days post-operatively. Morphological changes in the native endothelium along the recipient vessel correlated well with the direction of blood flow and predicted patterns of turbulence. The morphology of the native endothelium was altered to reflect the direction and pattern (laminar versus turbulent) of blood flow by 3 days postoperatively. Based on endothelial morphology, very narrow zones of separation could be demonstrated between areas of laminar and turbulent blood flow. The degree of reendothelialization across the suture itself was greatly variable at 3 days and there seemed to be no relationship to the location of turbulent flow. PMID- 1588808 TI - Dilatation in anastomosed arteries can be an artifact of explantation. AB - Fusiform dilation of the anastomotic site was found at explantation in the majority of rabbit femoral arteries anastomosed with newly developed microclips. This observation was also noted at sutured anastomoses. The mechanism responsible for this morphologic finding was studied by the following experiments: 1) measuring and explanting anastomosed arteries relaxed with 20% lidocaine, 2) latex casts of microclipped arteries, 3) comparing angiographic and histologic morphometric data, and 4) examining synthetic vascular graft anastomoses with identical dilatation. The observations demonstrate that trauma associated with explantation (direct dissection and fixative perfusion) leads to arterial vasoconstriction, but focal medial damage at the anastomotic site prevents constriction at this site. PMID- 1588809 TI - Comparison of the influence of intralumenal irrigation solutions on free flap survival. AB - Heparin is commonly included in the irrigation solution used during microvascular surgery. Evidence has accumulated to indicate a beneficial effect of heparin on anastomotic patency, implying that its topical use is critical to success even in routine microvascular repairs. This investigation compared heparin and urokinase as additives to the irrigation solution (Ringer's lactate) used during rat groin free flap replantation. A newly trained microsurgeon performed all surgical procedures to lower the possible success rate through microsurgical inexperience and, thus, to create a stronger challenge for the topical irrigant. Solutions were administered on a blinded, randomized basis. Vessel patency and flap survival were followed for 7 days. No statistically significant differences were found between any of the treatment groups: patency and survival rates of 67% for heparin, 57% for urokinase, and 73% for controls (vehicle only). The flap failures that occurred may have been attributable to undetected technical errors due to the microsurgical inexperience of the surgeon. In a separate series, an experienced microsurgeon achieved 93% success using vehicle without additives for irrigation. These results suggest that topical heparin or urokinase is not essential for achieving high levels of success during microvascular surgery. PMID- 1588810 TI - Restoration of venous outflow by simultaneous creation of an arteriovenous shunt and pedicle flap using a rat model of foot replantation. AB - Replantation of amputated rat feet utilizing an efferent arteriovenous shunt constructed between the distal posterior tibial artery and the proximal posterior tibial vein, in the absence of all other venous drainage, provides an alternative pathway to the normal venous drainage in a replanted rat foot. However, this substitute venous drainage was insufficient to prevent progressive ischemia and necrosis of some or all of a replanted rat foot. When a cutaneous pedicle flap supplemented the arteriovenous shunt, venous drainage was much improved, tissue hypoxia and edema began to subside on the third day, severe tissue necrosis was prevented, and seven of eight feet replanted by this technique survived. These observations may be useful in replantation in humans when veins in the amputated part are too small to be used or so damaged that they cannot be repaired or reconstructed by a vein graft, but arteries can still provide a means of returning blood from the amputated part. Constructing an alternative pathway to the normal venous drainage pattern may allow severely damaged parts to survive after replantation. PMID- 1588811 TI - Anastomotic failure due to acute vasculitis in free flap transfer: a case report. AB - We report a case of anastomotic failure secondary to acute vasculitis in a free flap. Following transfer of a latissimus dorsi myocutaneous flap, massive hemorrhage from the anastomosis occurred six days postoperatively. This was associated with segmental infarctions of the areas of the flap, which was removed. Transmural necrosis of the thoracodorsal artery, secondary to acute vasculitis was demonstrated by histology. Subsequent biopsies revealed an autoimmune vasculitis. PMID- 1588812 TI - Overexpression and surface localization of the Chlamydia trachomatis major outer membrane protein in Escherichia coli. AB - The Chlamydia trachomatis major outer membrane protein (MOMP) is the quantitatively predominant surface protein which has important functional, structural and antigenic properties. We have cloned and overexpressed the MOMP in Escherichia coli. The MOMP is surface exposed in C. trachomatis and capable of eliciting protective antibodies in infected hosts, and therefore has potential as a candidate vaccine to prevent infection with this significant human pathogen. The recombinant MOMP clone, L2rMOMP, contained the entire MOMP gene including the encoded leader sequence. Large quantities of chlamydial MOMP were expressed, some of which was processed and translocated to the E. coli surface. Surface localization of the MOMP was demonstrated by the binding of anti-MOMP monoclonal antibodies to the surface of the induced clone, and was visualized by fluorescence and electron microscopy. The induction of MOMP expression had a rapidly lethal effect on the L2rMOMP E. coli clone. Although no genetic system exists for Chlamydia, development of a stable, inducible E. coli clone which overexpresses the chlamydial MOMP permits a study of the biological properties of the MOMP, including the contribution of the MOMP variable segments to the topographical interactions which determine the antigenic structure responsible for human immune response. PMID- 1588813 TI - The autocatalytic processing of the subtilisin Carlsberg pro-region is independent of the primary structure of the cleavage site. AB - Subtilisins are extracellular seryl-proteases produced by bacilli (Markland and Emil, 1971). In addition to signal sequences, these proteases have N-terminal extensions (pro-regions) which have also been identified in several other proteases (Silen et al., 1988; Vasantha et al., 1984; Polhner et al., 1987; Henderson et al., 1987; Yanagida et al., 1986; Takagi et al., 1985). The pro region holds the pro-protease associated with the membrane and release of the protease takes place as a result of pro-region removal by autocatalytic processing (Egnell and Flock, 1991). In this report we describe the construction of four deletion-mutations in the gene encoding subtilisin Carlsberg at the junction between the pro-region and mature subtilisin Carlsberg. We found that the introduction of different deletions abolished the ability of subtilisin to undergo autocatalytic cleavage of the pro-region in cis, whereas cleavage by exogenous subtilisin could still occur in trans. Point mutations were also introduced in positions -5 to +4 around the pro-region and native subtilisin cleavage site. Processing of pro-subtilisin with the point mutations showed that the autocatalytic cleavage and recognition of this junction of the subtilisin Carlsberg pro-region is independent of the amino acid sequence around the cleavage site. PMID- 1588814 TI - Protein secretion in Pseudomonas aeruginosa: characterization of seven xcp genes and processing of secretory apparatus components by prepilin peptidase. AB - The xcp genes are required for the secretion of most extracellular proteins by Pseudomonas aeruginosa. The products of these genes are essential for the transport of exoproteins across the outer membrane after they have reached the periplasm via a signal sequence-dependent pathway. To date, analysis of three xcp genes has suggested the conservation of this secretion pathway in many Gram negative bacteria. Furthermore, the xcpA gene was shown to be identical to pilD, which encodes a peptidase involved in the processing of fimbrial (pili) subunits, suggesting a connection between pili biogenesis and protein secretion. Here the nucleotide sequences of seven other xcp genes, designated xcpR to -X, are presented. The N-termini of four of the encoded Xcp proteins display similarity to the N-termini of type IV pili, suggesting that XcpA is involved in the processing of these Xcp proteins. This could indeed be demonstrated in vivo. Furthermore, two other proteins, XcpR and XcpS, show similarity to the PilB and PilC proteins required for fimbriae assembly. Since XcpR and PilB display a canonical nucleotide-binding site, ATP hydrolysis may provide energy for both systems. PMID- 1588815 TI - Further studies on Pseudomonas aeruginosa LasA: analysis of specificity. AB - Full elastolytic activity in Pseudomonas aeruginosa is a result of the combined activities of elastase, alkaline proteinase, and the lasA gene product, LasA. The results of this study demonstrate that an active fragment of the LasA protein which is isolated from the culture supernatant fraction is capable of degrading elastin in the absence of elastase, thus showing that LasA is a second elastase produced by this organism. In addition, it is shown that LasA-mediated enhancement of elastolysis results from the separate activities of LasA and elastase upon elastin. The LasA protein does not affect the secretion or activation of a proelastase as previously proposed in other studies. Furthermore, LasA has specific proteolytic capability, as demonstrated by its ability to cleave beta-casein. Preliminary analysis of beta-casein cleavage in the presence of various protease inhibitors suggests that LasA may be classified as a modified serine protease. PMID- 1588816 TI - Mutants of Rhodobacter sphaeroides lacking one or more pigment-protein complexes and complementation with reaction-centre, LH1, and LH2 genes. AB - The photosynthetic apparatus of Rhodobacter sphaeroides is comprised of three types of pigment-protein complex: the photochemical reaction centre and its attendant LH1 and LH2 light-harvesting complexes. To augment existing deletion/insertion mutants in the genes coding for these complexes we have constructed two further mutants, one of which is a novel double mutant which is devoid of all three types of complex. We have also constructed vectors for the expression of either LH1, LH2 or reaction-centre genes. The resulting system allows each pigment-protein complex to be studied either as part of an intact photosystem or as the sole complex in the cell. In this way we have demonstrated that reaction centres can assemble independently of either light-harvesting complex in R. sphaeroides. In addition, the isolation of derivatives of the deletion/insertion mutants exhibiting spontaneous mutations in carotenoid biosynthesis provides an avenue for examining the role of carotenoids in the assembly of the photosynthetic apparatus. We show that the LH1 complex is assembled regardless of the carotenoid background, and that the type of carotenoid present modifies the absorbance of the LH1 bacteriochlorophylls. PMID- 1588817 TI - Many group A streptococcal strains express two different immunoglobulin-binding proteins, encoded by closely linked genes: characterization of the proteins expressed by four strains of different M-type. AB - Most group A streptococcal strains are able to bind immunoglobulin (Ig) in a non immune manner, and the majority of these strains bind both IgA and IgG. Using molecular cloning and immunochemical techniques, we have purified and characterized the Ig Fc-receptors expressed by four such strains. Two of the strains express a novel type of receptor, designated protein Sir, which binds IgA and IgG of all subclasses, and therefore has broader reactivity than any Fc receptor previously described. The other two strains express protein Arp, a receptor that binds IgA of both subclasses, and also binds polyclonal IgG weakly. Characterization of the weak IgG-binding ability of protein Arp shows that it binds only some monoclonal IgG proteins, in particular those of the IgG3 subclass. The four strains studied here were unexpectedly found to also express a second Ig-receptor, called protein Mrp, encoded by a gene closely linked to the gene for the first receptor. The Mrp protein does not bind IgA, but it binds IgG molecules of the IgG1, IgG2 and IgG4 subclasses, and it also binds fibrinogen. Binding of fibrinogen has been reported to be a characteristic property of streptococcal M proteins, which suggests that the Mrp protein may be an M protein that also binds Ig. Taken together, all available evidence now indicates that most strains of group A streptococci express two different Ig-binding proteins, encoded by closely linked genes. PMID- 1588818 TI - Allelic exchange in Pseudomonas aeruginosa using novel ColE1-type vectors and a family of cassettes containing a portable oriT and the counter-selectable Bacillus subtilis sacB marker. AB - An improved method for allele replacement in Pseudomonas aeruginosa was developed. The two main ingredients of the method are: (i) novel ColE1-type cloning vectors derived from pBR322 and pUC19; and (ii) a family of cassettes containing a portable oriT, the sacB gene from Bacillus subtilis as a counter selectable marker, and a chloramphenicol-resistance gene allowing positive selection of both oriT and sacB. Introduction of plasmid-borne DNA into the chromosome was achieved in several steps. The DNA to be exchanged was first cloned into the new ColE1-type vectors. After insertion of the oriT and sacB sequences, these plasmid were conjugally transferred into P. aeruginosa and plasmid integrants were selected. Plating on sucrose-containing medium allowed positive selection for both plasmid excision and curing since Pseudomonas aeruginosa strains containing the sacB gene in single- or multiple copy were highly sensitive to 5% sucrose in rich medium. This procedure was successfully used to introduce an agmR mutation into P. aeruginosa wild-type strain PAO1 and should allow the exchange of any DNA segment into any non-essential regions of the P. aeruginosa chromosome. PMID- 1588819 TI - SecY variants that interfere with Escherichia coli protein export in the presence of normal secY. AB - As an approach for studying how SecY, an integral membrane protein translocation factor of Escherichia coli, interacts with other protein molecules, we isolated a dominant negative mutation, secY-d1, of the gene carried on a plasmid. The mutant plasmid severely inhibited export of maltose-binding protein and less severely of OmpA, when introduced into sec+ cells. It inhibited growth of secY and secE mutant cells, but not of secA and secD mutant cells or wild-type cells. The mutation deletes three amino acids that should be located at the interface of cytoplasmic domain 5 and transmembrane segment 9. We also found that some SecY PhoA fusion proteins that lacked carboxy-terminal portions of SecY but retain a region from periplasmic domain 3 to transmembrane segment 7 were inhibitory to protein export. We suggest that these SecY variants are severely defective in catalytic function of SecY, which requires cytoplasmic domain 5 and its carboxy terminal side, but retain the ability to associate with other molecules of the protein export machinery, which requires the central portion of SecY; they probably exert the 'dominant negative' effects by competing with normal SecY for the formation of active Sec complex. These observations should provide a basis for further genetic analysis of the Sec protein complex in the membrane. PMID- 1588820 TI - Identification and characterization of a novel Bacillus thuringiensis delta endotoxin entomocidal to coleopteran and lepidopteran larvae. AB - A new class of Bacillus thuringiensis delta-endotoxins, or insecticidal control proteins (ICPs), is defined by an apparently cryptic protein with a unique primary structure and novel entomocidal specificity for certain coleopteran and lepidopteran species. The discovery of a new group of ICPs will extend the use of this natural insecticide in integrated pest-management systems. PMID- 1588821 TI - Molecular characterization and regulation of the phosphoglycerate kinase gene from Trichoderma viride. AB - We have isolated the phosphoglycerate kinase gene (pgk) of Trichoderma viride and characterized its expression. Comparison of genomic and cDNA clones allowed the correct deduction of the intron boundaries and the 3'-end cleavage site of this gene. Primer extension analysis showed that transcription initiated at three start points between -296 and -298 bp upstream of the translational start codon. The promoter sequence contained a number of cis-acting sequences commonly found in eukaryotic promoters. The pgk transcript analysis of T. viride grown on defined carbon sources showed that neither rate nor growth phase greatly affects pgk expression. By contrast, when Trichoderma spp. were grown in the presence of cell walls of a phytopathogenic fungus as carbon source, pgk messenger levels dropped markedly. This suggests that pgk mRNA accumulation is specifically repressed in the simulated mycoparasitic state. PMID- 1588822 TI - Nonproductive exchanges: the use of isotopes gone astray. PMID- 1588823 TI - Plasma met-enkephalin in type I diabetes. AB - Physiological and pathological evidence suggests that opioid peptides may play a role in glucose homeostasis. We measured plasma levels of beta-endorphin (beta END) and met-enkephalin (met-ENK) in 22 type I diabetic patients and 15 healthy women (control group). No differences were observed in plasma beta-END levels, whereas plasma met-ENK levels were significantly higher (Student's t test, P less than .005) in diabetics than in controls before (68 +/- 3 pg/mL v 32 +/- 7 pg/mL) and 1 hour after, a standard meal and administration of insulin therapy (81 +/- 9 pg/mL v 32 +/- 7 pg/mL). This is the first report of met-ENK levels in insulin dependent diabetes mellitus (IDDM), and an impaired feedback of insulin/met-ENK is suggested. PMID- 1588824 TI - Effect of acute inhibition of lipolysis on operation of the glucose-fatty acid cycle in hepatic cirrhosis. AB - Hepatic cirrhosis is frequently associated with glucose intolerance and insulin resistance, but the mechanisms underlying the insulin insensitivity are unknown. Plasma concentrations of nonesterified fatty acids (NEFA) are typically elevated in cirrhosis, and the glucose-fatty acid cycle provides a mechanism by which fatty acids may play a role in regulating glucose metabolism. We have therefore investigated the effect of acute inhibition of lipolysis, using the nicotinic acid analogue, acipimox, in 10 male patients with cirrhosis. All subjects were studied in the postabsorptive state after a 10- to 12-hour fast and were given either acipimox 250 mg or a placebo orally 2 hours before a 75-g oral glucose tolerance test (OGTT) and an infusion of insulin (50 mU/kg/h) and glucose (6 mg/kg/min) (insulin sensitivity tests [IST]). The drug was taken in a double blind crossover design for each test. During the 2 hours following acipimox, there were rapid decreases in plasma NEFA, glycerol, and 3-hydroxybutyrate, confirming inhibition of lipolysis, while there were significant decreases in glucose, insulin, and C-peptide (P less than .001) compared with patients receiving the placebo. Acipimox blunted the increase in glucose after oral glucose loading and decreased incremental glucose concentration (from 579 +/- 76 to 445 +/- 65 mmol/min/L, P less than .02) and incremental insulin concentration (from 13.4 +/- 2.5 to 9.0 +/- 1.4 U/min/L, P = .056) in the OGTT. Improvements in classification of glucose tolerance were seen in five subjects. During the IST, significant reductions occurred in steady-state blood glucose (to 8.8 +/- 1 mmol/L, P less than .02) and C-peptide (to 3.0 +/- 0.5 nmol/L, P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588825 TI - The thermogenic and metabolic effects of food in liver cirrhosis: consequences on the storage of nutrients and the hormonal counterregulatory response. AB - The thermogenic effect of food and the rates of oxidation and storage of nutrients were evaluated by indirect calorimetry in 10 cirrhotic patients and seven normal controls for a 6-hour period, after they had consumed a standard meal supplying 15 kcal/kg body weight with 15%, 30%, and 55% protein, fat, and carbohydrate calories, respectively. Although the thermogenic response to food was not significantly lower in patients than in controls (51.6 +/- 13.5 v 72.2 +/ 8.8 kcal/6 h), patients exhibited a delayed and blunted increment of energy expenditure after the meal intake (P less than .025). The greater part of the glucose load was oxidized in patients (70.2 +/- 3.9% v 50.4 +/- 3.9% in controls; P less than .01), suggesting a defective glucose storage as glycogen. This result could be related to insulin resistance, which was evidenced by a large increase in glucose and insulin levels after the meal intake in patients (P +/- .001). Conversely, lipid oxidation was sharply reduced and de novo lipogenesis occurred in patients, so that the rate of lipid storage was increased. The profiles of circulating levels of catecholamines, thyroid hormones (free thyroxine [FT4] and triiodothyronine [T3]), and glucagon were assayed during the test. Norepinephrine and glucagon levels remained higher in patients throughout the test (P less than .001), whereas thyroid hormones stayed in the same range in the two groups. After an initial increase, glucose levels decreased sharply, inducing an activation of counterregulatory hormones, glucagon, and notably, epinephrine, for which the increment was correlated with the decrease of glucose (r = -.917; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588826 TI - Changes in body composition of patients with subnormal spontaneous secretion of growth hormone, during the first year of treatment with growth hormone. AB - The effects of 1 year of growth hormone (GH) therapy were studied in 10 subjects with subnormal spontaneous secretion of GH, whose ages ranged from 6.5 to 12.4 years. Height, weight, body fat percentage, total body potassium (TBK), and extracellular water (ECW) were measured prior to initiating the treatment, and thereafter at 6 months (period 1) and 12 months (period 2). Height velocity almost doubled during the year of treatment: 7.8 +/- 0.8 and 7.1 +/- 0.7 cm/yr (P less than .0001) during periods 1 and 2, respectively, as compared with 3.9 +/- 0.6 cm/yr pretreatment. Body fat percentage decreased during period 1 to 18.2% +/ 4.9%, versus 16.3% +/- 4.5% (P less than .02), but stabilized thereafter (16.3% +/- 4.9%). Mid-arm muscle circumference (MAMC) and TBK increased in accordance with the predicted values for age. Body mineral density (BMD) increased both in absolute and standardized terms. No changes were found in ECW during treatment. We concluded that GH treatment in children with subnormal spontaneous secretion of GH has mainly a lipolytic effect on body composition, and that resistance to the lipolytic effect develops during the course of therapy. PMID- 1588827 TI - Effects of lovastatin therapy on very-low-density lipoprotein triglyceride metabolism in subjects with combined hyperlipidemia: evidence for reduced assembly and secretion of triglyceride-rich lipoproteins. AB - We have previously reported decreased production rates of the major apolipoprotein B (apoB)-containing lipoproteins, very-low-density lipoproteins (VLDL), and low-density lipoproteins (LDL) in patients with combined hyperlipidemia (CHL) during treatment with lovastatin. In the present study, we determined the effects of lovastatin therapy on VLDL triglyceride (TG) metabolism. Plasma VLDL turnover was determined in six CHL patients, before and during lovastatin therapy. 3H-triglyceride-glycerol-specific activity data derived from injection of 3H-glycerol were analyzed by compartmental modeling. The effects of lovastatin on VLDL TG metabolism were compared with those previously determined on VLDL apoB metabolism in these subjects. Lovastatin therapy was associated with decreased concentrations of VLDL TG in five of six patients and decreased VLDL apoB concentrations in all six. VLDL TG production rates (PR) decreased in five patients, with the mean for the group decreasing from 14.1 +/- 7.1 to 10.3 +/- 4.0 mg/kg/h (P less than .05). VLDL apoB PR also decreased in five patients, with the mean decreasing from 21.8 +/- 20.3 to 12.2 +/- 9.0 mg/kg/d (P = .11). Changes in VLDL TG concentrations during lovastatin treatment were correlated with changes in VLDL apoB concentrations (r = .74, P = .09) and in VLDL TG PR (r = .91, P = .01). Changes in VLDL TG PR were also related to changes in VLDL apoB PR (r = .62, P = NS). There were no consistent changes in the fractional catabolic rates of either VLDL TG or VLDL apoB during lovastatin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588828 TI - Deiodination and deconjugation of the glucuronide conjugates of the thyroid hormones by rat liver and brain microsomes. AB - Radioiodinated thyroxine (T4) glucuronide (T4G) and triiodothyronine (T3) glucuronide (T3G), paired with T4 or T3, were incubated at 37 degrees C for 2 hours in the presence of dithiothreitol and microsomes that had been prepared from euthyroid rat liver or hypothyroid rat brain tissues, as sources of type I and type II iodothyronine 5'-deiodinases, respectively. Incubations with boiled microsomes served as controls. The incubated supernatant was analyzed by high pressure liquid chromatography (HPLC) for content of T4, T4G, T3, T3G, and combined T2 and T2G. The deiodination of T4G resulted from incubation with both liver and brain microsomes, but was somewhat less active than the deiodination of simultaneously incubated T4. All batches of microsomes studied also caused deconjugation of both T4G and T3G. The data are compatible with the hypothesis that T4G can serve as an alternate pathway for conversion of T4 to T3 in these tissues. PMID- 1588829 TI - A multicenter comparison of the effects of simvastatin and fenofibrate therapy in severe primary hypercholesterolemia, with particular emphasis on lipoproteins defined by their apolipoprotein composition. AB - This multicenter, double-blind, randomized study was designed to compare the effects of simvastatin (20 mg/d and 40 mg/d) and fenofibrate (400 mg/d) on plasma lipids, lipoproteins, apolipoproteins (apo), and lipoprotein particles defined by their apo composition (Lp A-I, Lp A-II:A-I, Lp E:B, Lp C-III:B) in primary hypercholesterolemia. After 6 and 10 weeks of therapy, both drugs lowered plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apo B. The effect on LDL and apo B was significantly more pronounced for simvastatin (P = .01). Simvastatin increased Lp A-I, but did not change Lp A-II:A-I, while fenofibrate decreased Lp A-I and increased Lp A-II:A-I. Lp E:B and Lp C-III:B were decreased with both drugs, but fenofibrate was significantly more effective in reducing these particles than simvastatin. This study demonstrates that both drugs have beneficial effects on the parameters positively or negatively correlated with the atherosclerotic risk, with simvastatin being more effective in reducing some of them. These results suggest that the drugs led to different structural modifications of the lipoproteins, which would not be revealed by examination of lipoprotein density classes. These differences are probably related to the different mechanisms of action of the agents. PMID- 1588830 TI - The metabolic response to various doses of fructose in type II diabetic subjects. AB - Eight men with untreated type II diabetes were given 480 mL water containing 15 g, 25 g, 35 g, and 50 g fructose orally, in random sequence. The same subjects were given the same volume of water as a control. They also were given 50 g glucose on two occasions for comparative purposes. Plasma glucose, urea nitrogen, and glucagon, and serum insulin, C-peptide, alpha-amino-nitrogen (AAN), nonesterified fatty acids (NEFA), and triglycerides were determined over the subsequent 5-hour period. The area responses to each dose of fructose were calculated and compared with the water control. The integrated glucose area dose response was curvilinear, with little increase in glucose until 50 g fructose was ingested. With the 50-g dose, the area response was 25% of the response to 50 g glucose. The insulin response also was curvilinear, but the curve was opposite to that of the glucose curve. Even the smallest dose of fructose resulted in a relatively large increase in insulin, and a near-maximal response occurred with 35 g. The area response to 50 g fructose was 39% of that to 50 g glucose. The C peptide data were similar to the insulin data. The AAN area response to fructose ingestion was negative. However, the response was progressively less negative with increasing doses. The glucagon area response was positive, but a dose response relationship was not apparent. The glucagon area response was negative after glucose ingestion, as expected. The urea nitrogen area response was negative, but again, a dose-response relationship to fructose ingestion was not present.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588831 TI - Prolactin responses to phenylalanine and tyrosine in phenylketonuria. AB - In normal subjects, ingestion of tyrosine or phenylalanine stimulates prolactin (PRL) secretion. In patients with phenylketonuria (PKU), we found normal PRL responses to phenylalanine, demonstrating that conversion of phenylalanine to tyrosine is not necessary for PRL stimulation. PKU patients also showed greater PRL responses to tyrosine during dietary phenylalanine restriction than when consuming an unrestricted diet; this finding is consistent with inhibition by phenylalanine of tyrosine transport across the blood-brain barrier. Such competitive inhibition of a normal brain function may serve as a model for some of the neurotoxic effects of phenylalanine in PKU. PMID- 1588832 TI - Metabolic abnormalities of the hyperglycemic obese Zucker rat. AB - In a cross-sectional study, we evaluated the metabolic profiles of lean (Fa/?) and obese (fa/fa) Zucker male rats at 4 to 8 months of age. Although all of the obese rats (N = 108) demonstrated glucose intolerance, most of the obese rats exhibited only mild elevations of fasted and fed plasma glucose. Only 14 of the obese rats were severely hyperglycemic, which resulted in substantial elevations of glycohemoglobin (GHb) levels. The nerve and lens levels of glucose, sorbitol, and fructose were elevated, and the myo-inositol was depleted in all hyperglycemic obese rats, but not in the euglycemic obese rats. With increasing duration of hyperglycemia, the neural myo-inositol level approached normal, while the lenses became cataractous. All obese rats had increased urinary albumin excretion (UAE), which was dependent on age (r = .45, P less than .02) and independent of hyperglycemia, glucosuria, and polyuria. In conclusion, although the euglycemic obese rats exhibited some diabetic abnormalities, the hyperglycemic obese Zucker rat more closely resembled the altered metabolic profile associated with type II diabetes mellitus. PMID- 1588833 TI - Guanidino compounds in serum, urine, liver, kidney, and brain of man and some ureotelic animals. AB - Guanidino compound levels were quantitatively determined in serum, urine, liver, kidney, and brain of man and of some ureotelic animals. The guanidino compounds were separated over a cation exchange resin, using sodium citrate buffers, and detected with the fluorescence ninhydrin method. Species-specific differences in the levels of some guanidino compounds in the studied ureotelic animals are shown. alpha-Keto-delta-guanidinovaleric acid is a naturally occurring guanidino compound in ureotelic animals, and is not restricted to the pathobiochemistry of hyperargininemic patients. The fasting serum levels observed in beagles are the same as those found in hyperargininemic patients. In serum, liver, and kidney, the homoarginine, beta-guanidinopropionic acid, and gamma-guanidinobutyric acid levels are the highest in rats. The last two compounds have the highest levels of the studied guanidino compounds, with the exception of creatinine, in kidney. Specific high levels of gamma-guanidinobutyric acid and argininic acid are found in brain of rabbits. PMID- 1588834 TI - Effects of dietary fish oil on myocardial ischemic/reperfusion injury of Wistar Kyoto and stroke-prone spontaneously hypertensive rats. AB - The purpose of the present study was to determine whether 15 weeks of dietary fish oil supplementation to Wistar Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR) would alter cardiac contractile performance. Isolated perfused working hearts were used to determine the effects of varying left atrial filling pressures on cardiac pump output and pressure development. In addition, the ability of these hearts to recover cardiac output after a 60-minute period of low-flow ischemia followed by 30 minutes of reperfusion was assessed. Myocardial high-energy phosphate levels and long-chain acylcarnitine content were measured. Fish oil supplementation had no effect on indirect tail-cuff systolic blood pressure of WKY rats, but produced a small decrease in systolic blood pressure of SP-SHR. In response to varying left atrial filling pressures, hearts from WKY rats and SP-SHR exhibited no major differences in aortic flow, left intraventricular diastolic pressure, systolic pressure, positive and negative rate of pressure change per unit of time (dP/dt), or relaxation time; however, coronary flow values were lower in SP-SHR groups relative to respective WKY groups. Fish oil supplementation had no effect on these cardiac parameters. When these hearts were subjected to ischemia and reperfusion, the recovery of cardiac contractile performance was significantly improved in fish oil-fed WKY and SP-SHR groups, compared with their corn oil-fed counterparts. There were no differences in the recovery of the above cardiac hemodynamic parameters between corn oil-fed WKY and SP-SHR. These results provide further support to the hypothesis that dietary fish oil can significantly reduce the mortality risk from cardiovascular disease. PMID- 1588835 TI - Intravenous infusion of diarginylinsulin, an insulin analogue: effects on glucose turnover and lipid levels in insulin-treated type II diabetic patients. AB - Diarginylinsulin is an intermediate in the conversion of proinsulin to insulin and is usually present in small amounts in vivo in humans. This study was designed to evaluate the following in insulin-treated type II diabetic patients: (1) the feasibility of an overnight intravenous infusion of diarginylinsulin, as compared with an overnight intravenous infusion of short-acting insulin, and the degree of early morning glycemic control; and (2) the effects of diarginylinsulin and human insulin on hepatic glucose production (HGO) in the postabsorptive state and on the glucose turnover rate and peripheral insulin sensitivity during an euglycemic hyperinsulinemic clamp. Diarginylinsulin and regular human insulin maintained a comparable degree of normoglycemia during the night, without significant glucose increases in the morning. Free-diarginylinsulin and free insulin concentrations were not significantly different, and (HGO) was 2.1 +/- 0.5 versus 2.1 +/- 0.4 mg/kg/min with diarginylinsulin and regular human insulin, respectively (NS). During the euglycemic clamp, glucose infusion rate per unit of diarginylinsulin or human insulin infused (M/I ratio) was similar, and HGO was equally suppressed with diarginylinsulin and regular human insulin. No significant differences were seen in NEFA and triglyceride levels. In conclusion, these results indicate that diarginylinsulin is as potent as regular human insulin; it is normalizes HGO in the postabsorptive state; and its hepatic and peripheral actions on glucose and lipids are comparable to those of human insulin during an euglycemic hyperinsulinemic clamp. PMID- 1588836 TI - Organic acid profiling in adipocyte differentiation of 3T3-F442A cells: increased production of Krebs cycle acid metabolites. AB - To try to find special metabolic characteristics of adipose tissue, we examined the organic acids released into the culture medium, which was changed every 48 hours, as 3T3-F442A mouse fibroblasts underwent differentiation to adipocytes under the influence of insulin and fetal calf serum. We identified 13 different organic acids, of which four (malate, fumarate, succinate, and 2 hydroxyglutarate) increased from threefold to 10-fold during an 18-day period of differentiation. After differentiation had occurred, the deletion of insulin from the culture medium resulted in a slight decrease in the concentration of malate, fumarate, and 2-hydroxyglutarate. Other acids were not affected, including 18 that we were unable to identify by gas chromatography-mass spectroscopy. No acid was found to be present only in the medium of either fibroblasts or adipocytes. PMID- 1588838 TI - Steroid hormone interconversions in human adipose tissue in vivo. AB - The objective of this study was to demonstrate directly, by measurement of arteriovenous concentration differences, the interconversion of steroid hormones in human subcutaneous adipose tissue in vivo. Simultaneous arterial (or arterialized) and adipose tissue-venous plasma samples were collected from eight men and seven women, for measurement of estradiol, estrone, testosterone, and androstenedione concentrations by radioimmunoassay. Despite the heterogeneity of the groups (premenopausal and postmenopausal women, one subject with insulin dependent diabetes mellitus), some very consistent findings emerged. Both estrogens were added to plasma during passage through adipose tissue in almost all subjects (P less than .01 for each hormone). In all the men but one, testosterone was removed from plasma, and the arteriovenous difference was correlated with the arterial concentration (r = .70, P = .05). In all the women but one (in whom there was no change), the testosterone concentration increased during passage through adipose tissue. The handling of androstenedione was less consistent. This study demonstrates the feasibility of direct measurement of the peripheral production or utilization of steroid hormones, and confirms the belief that adipose tissue is an important site for such interconversions. PMID- 1588837 TI - Effect of propranolol on calcium, phosphorus, and magnesium metabolic disorders in Graves' disease. AB - The purpose of this study was to determine whether propranolol alone can improve mineral metabolic disorders in thyrotoxicosis. Ten Graves' disease patients and 11 normal age- and sex-matched controls participated in the study. In the untreated Graves' patients, serum levels of calcium (Ca), calcium x phosphorus product (Ca x P), urinary Ca, phosphorus (P), magnesium (Mg), and hydroxyproline (Hp) were higher than in control subjects (P less than .05), intestinal Ca absorption was lower than in control subjects (P less than .05), and Ca, P, and Mg balance were negative (P less than .05). After 40 mg propranolol four times per day (qid) for 28 days, serum triiodothyronine (T3) had decreased (P less than .05), serum reverse triiodothyronine (rT3) increased (P less than .05), serum thyroxine (T4) remained unchanged (P greater than .05), serum Ca and urine Ca and Mg decreased (P less than .05), intestinal Ca absorption increased, Ca balance was corrected, and P and Mg balance was improved (P less than .05). Our results indicate that propranolol can improve the metabolic disorders in addition to the symptomatic manifestations of Graves' disease. The mechanism responsible for the improved mineral balance is unclear, but may be related to beta-adrenergic blockade, increased membrane stability, or a decrease in the thyrotoxic state caused by the therapeutically induced decrease in serum T3. PMID- 1588839 TI - Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity. AB - A blunted growth hormone (GH) response to several stimuli, including growth hormone-releasing hormone (GHRH), has been shown in obesity. Arginine (ARG) has been demonstrated to potentiate the GHRH-induced GH increase in normal subjects, likely acting via inhibition of hypothalamic somatostatin release. To shed further light onto the mechanisms underlying the blunted GH secretion in obesity, we studied the effect of ARG (0.5 g/kg infused intravenously [IV] over 30 minutes) on both basal and GHRH (1 micron/kg IV)-stimulated GH secretion. Eight obese subjects (aged 26.4 +/- 3.9 years; body mass index, 39.0 +/- 1.9 kg/m2) and eight normal control volunteers (aged 27.0 +/- 1.7 years; body mass index, 22.3 +/- 0.5 kg/m2) were studied. In obese subjects, the GH response to both GHRH and ARG was lower (P less than .01 and P less than .002, respectively) than in controls. ARG potentiated the GH response to GHRH in obese patients (P less than .0003). However, in these patients, the GH secretion elicited by GHRH, even when coadministered with ARG, persisted at reduced levels (P less than .005) when compared with controls. Basal insulin-like growth factor-1 (IGF-1) levels did not significantly differ in obese subjects and in normal subjects (161.1 +/- 37.0 v 181.0 +/- 12.8 micrograms/L). In conclusion, ARG enhances the blunted GHRH induced GH increase in obese patients, but the GH responses to ARG alone and to ARG + GHRH persist at lower levels than in normals. Thus, our results suggest the existence of a reduced pituitary GH pool in obesity. PMID- 1588840 TI - Effects of high fat-feeding to rats on the interrelationship of body weight, plasma insulin, and fatty acyl-coenzyme A esters in liver and skeletal muscle. AB - Rats fed a high-saturated fat diet consumed more energy, gained more weight, and displayed hyperinsulinemia (P less than .05) without an elevation in the fasting plasma glucose level, compared with animals on two different high-carbohydrate diets. The total fatty acyl-coenzyme A (CoA) concentration was 18% (P less than .0001) and 46% (P less than .0001) higher in liver and skeletal muscle, respectively, from rats fed the high-fat diet compared with each of the other diet groups. Major long-chain fatty acyl-CoA molecular species of both tissues in high fat-fed rats reflected the fatty acid profile of the diet. Approximately 29%, 21%, and 16% of total liver and skeletal muscle fatty acyl-CoAs were comprised of oleoyl-CoA, palmitoyl-CoA, and stearoyl-CoA, respectively. The amounts of these three fatty acyl-CoA esters were significantly higher in liver and skeletal muscle after high-fat feeding than with the other diet treatments (P less than .0001). In contrast, the concentration of linoleoyl-CoA was lower in both tissues after high-fat feeding (P less than .0001). In rats fed the high-fat diet, plasma insulin levels were significantly correlated with gain in body weight or body weight (r = .80, P less than .001 for insulin and gain in body weight; r = .73, P less than .001 for insulin and body weight). Total fatty acyl CoA ester content in liver and skeletal muscle was also strongly correlated with the plasma insulin concentration in high fat-fed rats (r = .80, P less than .001 for liver; r = .78, P less than .001 for skeletal muscle).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588841 TI - Effects of haemolysins of groups A and B streptococci on cardiovascular system. AB - Anaesthetized New Zealand white rabbits and rats were either injected or infused with streptolysin S and group B streptococcal haemolysins in order to observe the haemodynamic actions of these haemolysins. Results showed that streptolysin S had little or no effect. In contrast, group B streptococcal haemolysin showed significant hypotensive action as manifested in rapid reduction of systolic, mean, diastolic and pulse pressures, and a limited number of deaths due to shock. PMID- 1588842 TI - Morphological and ultrastructural changes induced by sublethal concentrations of an anionic detergent on Ictalurus species barbel taste buds. AB - Morphological and ultrastructural changes were studied in Ictalurus sp. barbel taste buds (TBs), exposed to sublethal concentrations (3 ppm) of sodium alkylbenzene sulphonate for periods varying from 3 to 15 days. No significant alterations were noted after 3 days while, after just 6 days damage began to appear. The blood vessels were dilated and larger, more numerous intercellular spaces were observed between the light and dark TB cells than were to be found in the controls, but the basal portion of the TB was unaltered. After 9-12 days the most prominent features were the rupture of the plasma membranes, loss of microvillar organization of the light and dark cells as well as an increase in cytoplasmatic vacuolization. The skin was damaged and the germinative layer of the epidermis appeared activated and its height had increased. About 30% of the TBs were affected, and after 15 days they were severely damaged, whilst the feeding behaviour changed from day 6 onwards. PMID- 1588843 TI - Bacteroides and Staphylococcus glycocalyx: chemical analysis, and the effects on chemiluminescence and chemotaxis of human polymorphonuclear leucocytes. AB - Glycocalyx (or slime), which is an important virulence factor of many pathogenic bacteria, was isolated from Bacteroides fragilis, Bacteroides thetaiotaomicron and Staphylococcus epidermidis. Organisms were grown for 24 h in a chemically defined, dialysable liquid medium. Bacteria were centrifuged and the supernatant was concentrated and dialysed against distilled water. Total carbohydrate and protein were estimated using standard methods. Thin layer and gas-liquid chromatography of trifluoro acetic acid hydrolysed and non-hydrolysed samples provided evidence for the presence of polysaccharide, the absence of nucleic acids and lipopolysaccharide and for the identification of the individual sugar residues. Glucose, mannose and galactose (B. fragilis), glucose (B. thetaiotaomicron), and glucose and heptose (S. epidermidis) were the sugar residues detected. Uronic acid and hexosamine were detected in all species. Glycocalyx preparations (1 mg/ml) from Bacteroides and Staphylococcus significantly inhibited the chemiluminescence and chemotactic responses of viable human polymorphonuclear leucocytes (PMNL), but were not toxic for PMNL. PMID- 1588844 TI - Adhesion of Proteus mirabilis and Proteus vulgaris to uroepithelial cells following exposure to various antimicrobial agents. AB - The effect of subinhibitory concentrations of netilmicin, ceftriaxone, cefotaxime, aztreonam and piperacillin on the adherence of Proteus species to uroepithelial cells was examined. Bacterial adhesion to human uroepithelial cells, measured microscopically, was affected by all five antibiotics but to different extents. The most effective was netilmicin. There was a correlation between the decreased rate of bacterial attachment and morphological changes in the drug-exposed bacteria. PMID- 1588845 TI - [Staphylococcal biotyping and the use of computers]. AB - Ninety coagulase negative staphylococci isolated from various clinical specimens in Clinical Microbiology laboratory of Hacettepe University Faculty of Medicine, were biotyped using a special computer program. Types of 30 strains isolated from pus were found to be S. epidermidis (36.7%), S. haemolyticus (20%), S. simulans (13.3%) and S. hominis (10%) respectively. Among the strains isolated from blood S. epidermidis was again the predominant microorganism (40%), followed by S. haemolyticus (20%) and S. simulans (10%). PMID- 1588846 TI - [Phage typing of Pseudomonas aeruginosa strains from various sources]. AB - In this study, 103 strains of P. aeruginosa, isolated from various clinical specimens were typed by phage technique with a set of 22 phages. Phage typing procedure gave 29 different phage patterns. Ninety one of 103 P. aeruginosa strains could be typed, the other 12 strains could not be typed because of they have no sensitivity against test phages, studied. As a result of this study, phage typing technique is useful for the observation of epidemiological P. aeruginosa infections, but phage patterns have got significance only for the local environments. PMID- 1588847 TI - [Determination of Toxoplasma IgM by ELISA in maternal blood and cord blood of infants born with abnormalities or fetal death]. AB - In this study, Toxoplasma IgM antibodies in serum samples of 54 women who had maternal problems like abortion, preterm, fetal exitus, delivery with pediatric anomalies have been investigated with ELISA. In the cord sera of babies of these mothers, Toxo-IgM has been investigated too. Six mothers have been found to be Toxo-IgM seropositivity (11.11%). Toxo-IgM has been found negative in all of the cord samples. Three of Toxo-IgM positive mothers had fetal exitus and one of them had intrauterine growth retardation. One pregnancy has been terminated as abortion, the other as newborn with multiple anomalies. We have found out that active, latent or reactive toxoplasmosis have to be discriminated and for this purpose detection of Toxo-IgM levels is useful. PMID- 1588848 TI - [Microorganisms isolated from chronic suppurative otitis media and their antimicrobial sensitivities]. AB - In this study mycologic and bacteriologic cultures were made in 100 patients who had chronic suppurative otitis media. We observed 58.8% pure, 35.3% mixed growth (more than one bacteria or bacteria and fungus) in the cultures. In pure cultures, we found mostly Proteus sp., S. aureus and Pseudomonas sp. respectively. In 134 bacteriologic cultures most frequently isolated bacteria was S. aureus (36.6%). In Sabouraud agar, we found mostly Aspergillus sp. and Candida sp. (28.6%). In antimicrobial sensitivity test, gram negatives were found to be sensitive mostly to ofloxacin (73.5%), pseudomonas was found to be sensitive mostly to tobramycin (70%). In the staphylococci the antimicrobic which had the highest sensitivity rate was gentamicin (75.5%), but at the same time we observed 24.5% resistance to this antimicrobic agent. Following this respectively, ofloxacin 71.4% sensitivity 4.1% resistance, cefuroxime 69.4% sensitivity 10.2% resistance rate were detected. PMID- 1588849 TI - [Prevalence of G. vaginalis, Mycoplasma, Ureaplasma, T. vaginalis, yeast, N. gonorrhoeae and other bacteria in women with vaginal discharge]. AB - Vaginal discharge of 118 women attended to outdoor clinics of obstetrics and gynaecology at Medical Faculty of Ankara University (A.U.T.F.), have been examined. Direct microscopy has been made by means of wet mount, Gram and Giemsa staining. Vaginal pH has been measured, by 10% KOH the presence of "fishy odor" has been investigated. For culturing vaginal secretions in Amies transport medium have been brought to Microbiology Department of Ankara University, Faculty of Medicine Inoculations have been made on to Blood agar, MacConkey agar, Sabouraud Dextrose agar, New York City. Medium, % 5 Human blood bilayer Tween 80 Medium (HBT), Vivey Trichomonas Agar Medium and into M-broth and U9 broth. In this study, we have isolated 9 (7.62%) Gardnerella vaginalis, 41 (33.89%) Ureaplasma, 13 (11.01%) Mycoplasma, 25 (21.18%) yeasts, 4 (3.38%) Trichomonas vaginalis and 43 (36.46%) various bacteria, 26 cases were found to have polymicrobial etiology. PMID- 1588850 TI - [The local prevalence of group B streptococcus in pregnant women and newborn infants]. AB - In this study, group B streptococcus (GBS) were investigated in vaginal swabs obtained from 76 pregnant women and in samples of newborn infants obtained from different areas of their bodies. GBS were determined in 5.2% of women and 3.96% of infants. GBS were recovered in 15.4% of the women in their first pregnancy and in 13.3% of women in their second pregnancy. GBS could not isolated from the women in their third and more pregnancies. All eight species of GBS were sensitive to AMP + Sulbactam, Clavulanic acid + Amox, Lincomycin, Clindamycin, Penicillin G and SMZ + TMP. PMID- 1588851 TI - [The prevalence of intestinal parasites in primary school students in Trabzon and the importance of education of parasite patients]. AB - Hundred and forty stool samples obtained from fourth classes (10 years of age) of the primary school students were examined for intestinal parasites. In addition, effect of education and variety of education on parasitic diseases were investigated. Of the 140 students 65% were found to be positive for intestinal parasites. Ascaris lumbricoides 15.7%, Trichuris trichiura 22.85%, Giardia intestinalis 7.14%, Ascaris lumbricoides + Trichuris trichiura 15.7%, Giardia intestinalis + Trichuris trichiura 3.57% were found. The infested students were treated with antiparasitic drugs, and were educated for parasitic diseases. 50% of the student were given brochure, the others were given brochure and verbal education. After 1.5 month control stool samples were taken. In both groups infestation rate was 27.14%. Ration was 18.57% in only brochure given group, and 8.57% in brochure and verbal education given group. The difference between two group was meaningful (X2 = 3.89 P less than 0.05). PMID- 1588852 TI - [Intracranial tuberculoma]. AB - Intracranial tuberculoma is one of the most serious complication of tuberculosis. It generally accompanies tuberculous meningitis. Diagnosis is difficult. Computed tomography (CT) has greatly influenced the diagnosis and management. In this study, clinical and laboratory findings of three patients with intracranial tuberculoma were discussed. In CT study, intracranial tuberculomas were located at the level of brain stem in two patients and thalamic region in one patient. Although intracranial tuberculoma is uncommon in children, it must be included in the differential diagnosis of all tuberculous meningitis. This is especially important for the patients who have no BCG vaccination. PMID- 1588853 TI - [Isolation of phPAH 247 cDNA probe from pBR322 plasmids by mini-prep technique]. PMID- 1588854 TI - [Recombinant DNA technology]. AB - Recombinant DNA technology is a method depending on realization of genetic recombination events artificially. It became possible to obtain any ordered gene or its product with this method. Before production step, ordered gene is derived from original chromosome by endonuclease enzyme and integrated to a vector as a plasmid or a phage. After that this vector is transformed into a bacterium or a yeast. Then ordered gene or protein is produced in desired amounts by culturing these microorganisms. PMID- 1588855 TI - [The importance of antibiotic resistant mutants of Rhizobium and their uses in ecology]. AB - Almost all aspects of research into the ecology of Rhizobia rests on the recognition of the strains. Marker techniques can be conveniently grouped into the three categories (a) those based on serological differences, (b) genetic markers, and (c) other natural markers. In this article, the genetically marked strains of Rhizobia and their use in the ecology will be discussed. PMID- 1588856 TI - Why does Australia have no national drug policy? PMID- 1588857 TI - The value of Doppler ultrasound in obstetrics. PMID- 1588858 TI - Intrauterine transfusion in Rh alloimmunisation. PMID- 1588859 TI - Newer antihypertensive agents in pregnancy. PMID- 1588860 TI - Diversity of blood pressure recording during pregnancy: implications for the hypertensive disorders. AB - OBJECTIVE: To determine the number and type of methods used to measure blood pressure (BP) in pregnant women. DESIGN: Questionnaires were distributed to obstetricians and midwives concerning: method of recording BP (arm used, subject position, Korotkoff sounds recorded); accuracy of recording BP (cuff size, sphygmomanometer calibration); and definitions of hypertension in pregnancy. PARTICIPANTS: Obstetricians (academic, staff and private) in Sydney; members of the New South Wales Midwives' Association. MAIN RESULTS: Responses were received from 85 obstetricians (55% of those surveyed) and 173 midwives (43%); the overall response rate was 46%. Almost 80% of respondents agreed that diastolic BP above 90 mmHg constituted hypertension during pregnancy but at least six different methods were used to obtain BP readings, with a potentially large variability in the BP so obtained. Forty-five per cent of obstetricians and 72% of midwives stated that they always used a large cuff when necessary. Few had had their sphygmomanometer calibrated within the previous two years. CONCLUSIONS: There is considerable variability in the way BP is recorded in pregnant women. Hypertension in pregnancy may therefore be over or under diagnosed according to the method employed and there is an urgent need for international consensus on how to measure BP accurately in pregnancy. PMID- 1588861 TI - Trends in causes and treatment of infertility at Flinders Medical Centre, Adelaide, 1976-1989. AB - OBJECTIVE: To describe the causes of infertility among couples presenting to a fertility clinic over a period of 14 years. Changes in treatment methods over the same period are described. DESIGN: A retrospective analysis of records of patient age, date of first visit, duration and cause of infertility, treatment and outcome. SETTING: A fertility clinic set in a large public hospital. Patients are referred by both general gynaecologists and general practitioners. PATIENTS: From 1976 to 1989 (inclusive) 2895 couples who had engaged in unprotected intercourse for at least 12 months without conceiving attended the clinic. RESULTS: Three major diagnostic categories were considered; these embraced aetiological factors relating to semen, ovulation, and pelvic anatomy. Investigation of the causes of infertility after a couple's first visit showed these to be a semen defect in 22%, irregular cycles or anovulation in 29%, and a pelvic disorder in 57%. The incidence of semen defects as the cause remained constant between 1976 and 1989 while that of ovulation "problems" declined from 42% in 1976 to 13% in 1989. In contrast, the incidence of pelvic dysfunction increased from 40% in 1976 to 68% in 1989, predominantly due to an increased diagnosis of endometriosis. The principal treatments were ovulation induction/cycle regulation (51%), in-vitro fertilisation/gamete intrafallopian transfer (42%), and donor insemination (18%). CONCLUSIONS: Provided patient information is accurately and consistently recorded a Fertility Audit is a useful window on the activates of a Fertility Clinic and serves to highlight areas which warrant further investigation. PMID- 1588862 TI - A cost-effectiveness analysis of hormone replacement therapy in the menopause. AB - OBJECTIVE: To evaluate the cost-effectiveness of hormone replacement therapy in the menopause with particular reference to osteoporotic fracture and myocardial infarction. DESIGN: The multiple-decrement form of the life table was the mathematical model used to follow women of age 50 through their lifetime under the "no hormone replacement" and "hormone replacement" assumptions. Standard demographic and health economic techniques were used to calculate the corresponding lifetime differences in direct health care costs (net costs in dollars) and health effects ("net effectiveness" in terms of life expectancy and quality, in "quality-adjusted life-years"). This was then expressed as a cost effectiveness ratio or the cost ($) per quality-adjusted life-year (QALY) for each of the chosen hormone replacement regimens. SETTING AND PATIENTS: All women of age 50 in New South Wales, Australia (n = 27,021). RESULTS: The analysis showed that the lifetime net increments in direct medical care costs were largely contributed by hormone drug and consultation costs. Hormone replacement was associated with increased quality-adjusted life expectancy, a large percentage of which was attributed to a relief of menopausal symptoms. Cost-effectiveness ratios ranged from under 10,000 to over a million dollars per QALY. Factors associated with improved cost-effectiveness were prolonged treatment duration, the presence of menopausal symptoms, minimum progestogen side effects (in the case of oestrogen with progestogen regimens), oestrogen use after hysterectomy and the inclusion of cardiac benefits in addition to fracture prevention. CONCLUSIONS: Hormone replacement therapy for symptomatic women is cost-effective when factors that enhance its efficiency are considered. Short-term treatment of asymptomatic women for prevention of osteoporotic fractures and myocardial infarction is an inefficient use of health resources. Cost-effectiveness of hormone replacement in asymptomatic women is dependent on the magnitude of cardiac benefits associated with hormone use and the treatment duration. PMID- 1588864 TI - Otitis externa in general practice. AB - Otitis externa seen in general practice is most commonly bacterial in origin and is readily diagnosed and treated if a few simple guidelines are followed. These guidelines are discussed with emphasis on distinguishing the condition from otitis media, performing adequate ear toilet and choosing appropriate topical medications and vehicles for their application. PMID- 1588863 TI - Obstetric and birthweight differences between Vietnam-born and Australian-born women. AB - OBJECTIVES: To measure the frequency of obstetrical complications and assess the outcome of pregnancies in Vietnam-born mothers; to compute birthweight percentile charts for their infants; and to compare these parameters in Vietnam-born women with those of a control group of Australian-born women. DESIGN: A retrospective study of all pregnancies in Vietnam-born and Australian-born mothers managed in the Mercy Hospital for Women over a 10-year period, 1979-1988 inclusive. SETTING: The Mercy Hospital for Women provides primary and secondary obstetric care to public and private patients. PATIENTS: All women born in Australia or Vietnam who delivered in the Mercy Hospital for Women, Melbourne, over the 10-year period and their infants. Twins, stillborn babies and infants with congenital malformations were not included in the calculation of birthweight percentiles. RESULTS: Gestational diabetes (7.3% v. 4.3%, P less than 0.0001) and low oestriol excretion (14.4% v. 10.8%, P less than 0.0001) were more common whereas essential hypertension (0.3% v. 1.2%, P less than 0.001) and pre eclampsia (3.7% v. 8.6%, P less than 0.0001) were less common among Vietnam-born mothers. Intervention for labour and delivery was less common among Vietnam-born mothers: induction of labour (7.1% v. 24.7%, P less than 0.0001) and forceps delivery (17.8% v. 21.9%, P less than 0.001); caesarean section rates were similar. Infants of Vietnam-born mothers were significantly lighter than those of Australian-born; percentile charts for birthweight and gestational age are presented. CONCLUSIONS: Pregnancies among Vietnam-born women migrants in Australia were associated with few complications in spite of a higher incidence of gestational diabetes and a low oestriol excretion. The infants were lighter than those born to Australian born mothers. Our percentile charts for birthweight relative to gestational age will provide a more accurate assessment of intrauterine growth for these infants. PMID- 1588865 TI - Part-time training with the Family Medicine Programme. PMID- 1588866 TI - The doctor-patient relationship in general practice. PMID- 1588867 TI - Queen Anne's "seventeen disappointments". PMID- 1588868 TI - Hepatitis due to nitrofurantoin. AB - OBJECTIVE: To report three cases of hepatitis related to the use of nitrofurantoin. CLINICAL FEATURES: Two patients who had been taking nitrofurantoin for several years, presented with severe liver failure. In both, the drug had been continued despite evidence of liver injury. A third patient presented with acute hepatitis after six weeks of nitrofurantoin therapy. INTERVENTION AND OUTCOME: One of the patients with liver failure died and the other underwent a successful liver transplantation. The third patient recovered after withdrawal of the drug. CONCLUSION: These cases emphasise the potential for serious hepatic reactions with nitrofurantoin, the danger of continuing the drug once liver damage has occurred and the need for careful monitoring of liver function during long-term therapy. PMID- 1588869 TI - Human ectopic fascioliasis in Australia: first case reports. AB - OBJECTIVE: To describe the manifestations of two cases of migratory ectopic fascioliasis diagnosed in Australia, including the first report of lymphatic infection. PRESENTATION: Both patients presented with acute, superficial swellings. In the first, a 46-year-old woman, the lump was found to be a cervical lymph node containing a mature Fasciola hepatica which had released eggs into surrounding tissues. The second patient was a 34-year-old male abattoir worker, in whom the subcutaneous lesion resembled an infected sebaceous cyst and contained an immature fluke. FINDINGS: Both lesions were resected and diagnosed histologically. Fasciola eggs were not found in the faeces of either patient. Blood eosinophilia was not detected in either case. A serological test for fascioliasis was carried out in the second case and the result was positive. In both cases, infection was probably acquired in Australia, although neither patient had eaten watercress. OUTCOME: Neither patient was specifically treated with anthelminthic agents, and neither suffered further complications. CONCLUSION: Migratory fascioliasis occurs in Australia. It can present as superficial or deep focal lesions, not necessarily in association with peripheral blood eosinophilia or Fasciola eggs in faeces. Serological tests may be helpful in diagnosing such cases. PMID- 1588870 TI - Rational prescribing: the challenge for medical educators. PMID- 1588871 TI - Doctor in pain--learning as a patient. PMID- 1588872 TI - Anti-HIV-1 testing results are reported rapidly by Australian laboratories: a national survey. AB - The National HIV Reference Laboratory undertook a one-week prospective study to determine the time taken by Australian human immunodeficiency virus antibody (anti-HIV) testing laboratories to test a sample and report an anti-HIV-1 result. The study showed that more than 86% of the sample results were reported by the second day and more than 98% by the fourth day after receipt of the specimen. PMID- 1588873 TI - Exemptions from wearing motorcycle helmets. PMID- 1588874 TI - Metastatic liver cancer: no cause for nihilism. PMID- 1588875 TI - SPPS, hypotension and ACE inhibitors. PMID- 1588876 TI - 1988 survey of career intentions of 1983 and 1984 Western Australian medical school graduates. PMID- 1588877 TI - Sodium cromoglycate for ACE inhibitor cough. PMID- 1588878 TI - Health and economic cost of chickenpox in child care. PMID- 1588879 TI - Drug interactions with fluconazole. PMID- 1588880 TI - Silicone breast implants. PMID- 1588881 TI - The Royal Commission into Aboriginal Deaths in Custody. PMID- 1588882 TI - General practice financing: report of a "think tank". PMID- 1588883 TI - Inguinal surgery for debilitating chronic groin pain in athletes. PMID- 1588884 TI - Nebulised budesonide. PMID- 1588885 TI - Traumatic avulsion of right coronary artery: 30-year follow-up. PMID- 1588886 TI - Blue-green algae: fact or fantasy? PMID- 1588887 TI - Impaired hepatic metabolism of i.v. lignocaine as an index of cellular damage from carbon monoxide poisoning. PMID- 1588888 TI - Unexpected response to treatment of falciparum malaria illness. PMID- 1588889 TI - Factitious patients with fictitious disorders: a note on Munchausen's syndrome. PMID- 1588890 TI - The compression of morbidity hypothesis: promise and pitfalls of using record linked data bases to assess secular trends in morbidity and mortality. AB - Individuals who are 65 years of age and older have exhibited unprecedented declines in mortality over the past few decades in the United States. Whether this increased survival has been accompanied by delays in the onset of disease or greater age-specific morbidity remains unanswered because of a paucity of reliable information on secular trends in age-specific disease incidence and survival. The Rochester Epidemiology Project (REP) is one of a few existing medical record linkage systems that offer promise of providing some of the necessary information. Several examples are presented that illustrate the potential of medical record-linked data bases for examining secular trends in the association between age at onset of disease and age at death. PMID- 1588891 TI - Creating outcomes-based systems for quality and malpractice reform: methodology of accelerated compensation events (ACEs). AB - Today's unduly erratic and expensive payment system for medical malpractice undercuts its own goal of compensating victims. Its lack of scientific legitimacy hampers its other main goal of deterring injury. Reform is needed, but most "tort reform" fails to make fundamental changes and does not promote quality of care. Alternative systems using "Accelerated Compensation Events" (ACEs) offer a better way to replace or improve judicial resolution of liability claims as well as independent, quality-oriented reform. ACEs do not cover all injuries, just classes of adverse outcomes that are normally avoidable, given good care. This article explains the scientific methodology of ACE development and the benefits of ACE-based reforms. PMID- 1588892 TI - Cigarette smoking and lifetime medical expenditures. AB - The cumulative impact of excess medical care required by smokers at all ages while alive outweighs shorter life expectancy, and smokers incur higher expenditures for medical care over their lifetimes than never-smokers. This accords with the findings by Manning et al. (1989) of positive lifetime medical care costs per pack of cigarettes, but disagrees with the results found by Leu and Schaub (1983, 1985) for Swiss males. The contradictory conclusions of the analyses are undoubtedly due to a large difference in the amount of medical care used by smokers relative to neversmokers in the United States and Swiss data. Excess expenditures increase with the amount smoked among males and females so that lifetime medical costs of male heavy smokers are 47 percent higher than for neversmokers when discounted at 3 percent. Each year more than one million young people start to smoke and add an extra $9 to $10 billion (in 1990 dollars discounted at 3 percent) to the nation's health care bill over their lifetimes. Given the smoking behavior, medical care utilization and costs of care, and population size embedded in the data used in this analysis, I have concluded that in the first five years from baseline the population of smokers aged 25 and over incurs excess medical expenditures totaling $187 billion, which is $2,324 per smoker. The excess cost of medical care associated with cigarette smoking is 18 percent of expenditures for hospital care, physicians' services, and nursing-home care required by all persons (smokers and neversmokers) aged 25 and over. In the absence of large and rapid changes in the values of the underlying parameters, $187 billion, 18 percent of medical expenditures, can be taken as the premium currently being paid every five years to provide medical care for the excess disease suffered by smokers. Even without the addition of any new smokers, the present value of the bill that will be incurred for excess medical care required by the current population of smokers over their remaining lifetimes is high. The civilian noninstitutionalized population of cigarette smokers in 1985 who are age 25 and older is expected to incur over its remaining lifetime excess medical expenditures of $501 billion, or $6,239 per smoker. It is possible that future changes beyond recent historical trends in the habits of those who currently smoke, such as reductions in the amount smoked, higher rates of quitting, whether occurring fortuitously or brought about by design, may result in lower costs of smoking than estimated.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1588893 TI - [Diagnostic imaging in cases of physical abuse of children]. AB - Following a few comments regarding the historical development, preliminary definitions and early studies on battered child syndrome, the Authors give an overall clinical semeiological picture, focusing on the anatomo-radiological characteristics of the most common bone and non-bone lesions. In addition traditional (X-ray) and more advanced methods of image diagnosis (ultrasonography, CT, RM) are examined and their utility in the study of the battered child is evaluated. PMID- 1588894 TI - [A computer program to retrieve and record ISTAT codes related to pediatric diagnosis]. AB - The paper describes a computer program that retrieves ISTAT codes increasing the efficiency of the retrieving time spent with traditional methods storing the obtained information in a suitable data-base, which may be lately explored by means of commercial programs. To increase the detail of the stored data, many of the official codes have been expanded with an extra character. Some results obtained from an experience conducted at the Pediatric Division of Crema Hospital are also reported. PMID- 1588895 TI - [The Gaslini Medical-Surgical Emergency Service. Organizational and functional aspects]. AB - The Authors take into account the organization of the medical emergency service at Gaslini children's hospital. Emergency medicine has been developing as a pediatric subspecialty, involving medical surgical and intensive care units to meet the peculiar needs of the acutely ill child. Moreover epidemiological data regarding all kinds of activity have been collected; they show a decrease in admitted patients and an increase in outpatients. These data undertime how effectively the service can act as a filter as well. PMID- 1588896 TI - [Changes in dynamic respiratory volumes in obese children and adolescents related to weight loss and sex]. AB - Obesity is associated with various alterations in lung function in adults. These alterations appear to be proportional to the degree of EP and the beneficial effect of weight loss on respiratory function has been reported. Therefore, in 35 children and adolescents affected by essential obesity of medium-severe degree, we have evaluated the following parameters: FVC (forced vital capacity), PEF (peak expiratory flow), FEV1 (forced expiratory volume), FEV75, FEV50, FEV25, before and after six months of dieting. Twelve subjects (34%) showed at least a pathologic value of PEF and/or FEV50 before dieting. All the female patients normalized their parameters after six months of dieting, whilst 5 out of 7 males still showed pathologic respiratory indexes, although a similar weight loss was obtained in the two groups of patients. Our study enhances the presence of respiratory functions derangements in a significant percentage of children with medium-severe degree of obesity. A careful monitoring of these subjects is therefore necessary, in order to prevent further progression of the lung function damage. After dieting the pulmonary function improved in female patients only, suggesting that factors other than the EP are involved in the pathogenesis of the respiratory alterations. PMID- 1588897 TI - [Lactate dehydrogenase and its isoenzymes in respiratory diseases in children]. AB - Total Lactate Dehydrogenase (LD, EC 1.1.1.27) activity in serum and LD isoenzymes were quantified in 161 children (51 with pneumonia at the time of diagnosis, 60 hospitalized for asthma in acute period and 50 healthy subjects) to ascertain the relationship of these markers with injury of lung tissue. No statistical variations, between different groups in total activity, were found. Significantly decreased proportions of LD1 (p less than 0.000001) and of LD2 (p less than 0.000001) with simultaneous increase of LD4 (p less than 0.000001) and LD5 (p less than 0.000001) resulted in children with pneumonia, as to asthmatic or healthy subjects. Investigators conclude that LD should be determined in every patient with pneumonia because of the presence of a specific LD isoenzyme pattern. PMID- 1588898 TI - [Role of digestive endoscopy in the diagnosis of primary intestinal lymphangiectasis. Presentation of 2 cases]. AB - This article describes two new cases of primary intestinal lymphangiectasia: the first one refers to a 10-years-old girl, who failed to thrive, while the second one was discovered in a 19-months-old female infant, who presented with anasarca. In both cases gastroduodenal endoscopy allow us to put the diagnosis, revealing the presence of the typical duodenal lesions, due to dilatation of the lymphatic vessels and loss of the lymph. The typical endoscopic features found in both cases are here described; at the same time, the major role of the intestinal biopsy via endoscopic route is outlined, since this is the only method which allow to perform targeted biopsies. PMID- 1588899 TI - [Severe sideropenic anemia in a young middle-distance runner]. AB - In recent years several cases of anemia (iron deficiency) have been reported in adults who participate in long-distance running although its etiology has not been entirely explained. We report the case of a 16-year-old girl who had participated in middle-distance running at a competitive level for about three years and who had been admitted to hospital because of a progressive weakness and a reduction in her sporting performance. Evaluation revealed that the patient had a balanced diet, normal menstrual cycles and slight abdominal pain. The objective examination were negative except for the presence of a pronounced pallor of the skin and the mucous membranes. The blood count revealed Hb 7.5 g%, Ht 26%, GV 63 mu 3, the reticulocyte count was 10%, serum iron 9 micrograms/dl, serum transferrin 450 micrograms/dl and serum ferritin 4 ng/ml. All tests for constitutional anemia proved negative. Stool Hemoccult tests proved negative (these tests were carried out some weeks after the patient had stopped running). Her symptoms resolved after the beginning of iron treatment and her blood test results returned to normal. This case has been reported to draw attention to the existence of this problem in adolescents who practice sport. The knowledge of the problem night lead to a preventive scanning of young athletes and the presence of clinical manifestations would reduce the need for invasive tests. PMID- 1588901 TI - Multimodal evoked potentials in myotonic dystrophy (MyD). AB - By means of multimodal evoked potentials (EPs), we evaluated the central nervous system (CNS) involvement in 25 subjects suffering from myotonic dystrophy: brainstem auditory evoked potentials (BAEPs), middle-latency auditory evoked potentials (MLAEPs) and somatosensory evoked potentials (SEPs) from the upper limb were performed on all subjects, whereas only the 19 patients, whose clinical ocular abnormalities were slight, underwent pattern-electretinograms (PERGs) and pattern visual-evoked potentials (VEPs) in order to identify the site of lesion among visual pathways (retinal and/or retroretinal). PERGs were abnormal in 8/19 subjects, VEPs in 8/19 subjects (the two techniques were simultaneously abnormal in 8 eyes), BAEPs in 7/25 subjects, MLAEPs in 4/25 subjects (in one subject both BAEps and MLAEPs were abnormal) and SEPs were abnormal in 1/25 subjects. 13/25 of our subjects showed at least one EP that revealed a CNS involvement. The electrophysiological alterations were not correlated either with subject age or with disease duration. Multimodal EPs enabled us to demonstrate that CNS involvement in myotonic dystrophy is important and mainly affects the visual and auditory system. PMID- 1588900 TI - [Electrophysiologic data on myasthenic syndromes of the Lambert-Eaton type. A series of 23 cases]. AB - The electrophysiological data of 23 adult patients with Lambert-Eaton myasthenic syndrome (LEMS) have been reviewed. Lung carcinoma was disclosed in 17. In six cases with an EMG follow-up ranging between one and 17 years no carcinoma was detected. The results of repetitive nerve stimulation test (RNS) were not statistically different between the 2 groups. Low CMAP ulnar amplitude was present in all patients (mean: 1.7 mV). Decremental response at low rate of stimulation (3 Hz) was present in 17/20 (means: 30%). An abnormal incremental response at high rate of stimulation was present in all cases (mean: 826%). The authors emphasize the interest of a 50 Hz stimulation for 4 s. Increase of the 'F wave' amplitude was noticed in some cases. Electrophysiological changes suggestive of an associated mild neuropathy were noticed in eight patients but H reflex was present in 3/3 cases. SFEMG abnormalities were found in 6/6 cases. In one case, stimulated SFEMG showed more blockings and an increased jitter with low rate of stimulation. In one case the electrical pattern of RNS could be misinterpreted as myasthenia gravis in one tested muscle only. The author's results suggest that CMAP amplitude and RNS test could be used to appreciate the short-term improvement of LEMS with treatment and in some cases for the long-term follow-up. PMID- 1588902 TI - [Electromyographic, histoenzymologic and immunocytochemical aspects of affected muscles in HIV infection. Observations of five cases]. AB - In 5 acquired-immunodeficiency syndrome (AIDS) cases without peripheral neuropathy, we observed myogen clinical signs (diffuse amyotrophy of lower limbs or cramps) or an isolated increase in seric enzyme (LDH, CK). EMG abnormalities were observed in all cases: spontaneous activities (fibrillations and positive sharp waves) in 5 cases, myogenic signs in 2 case. Muscular biopsies were normal in 3 cases and showed myopathic changes in 1 case and polymyositis in another case. Antidystrophin and antilaminin antibodies reactions were altered in 1 case. The spontaneous activities together with these modifications could be in favour of a lesion at the membrane level. PMID- 1588903 TI - [Automatic analysis by computer of the visual suppression test of pendular rotatory vestibular nystagmus]. AB - This study presents an automatic computerized analysis of the visual suppression test of vestibular nystagmus. Visual suppression is measured during rotatory nystagmus examination. The amplitude variations and the frequency of the nystagmus are computed in the dark and in the light. This allows the computer to furnish with the help of an algorithm the percentage of nystagmus suppressed by ocular fixation. The results of the computerized analysis are compared to a qualitative evaluation. A percentage of 70% and more indicates a normal suppression reflex and corresponds qualitatively to a total or subtotal visual suppression. A percentage smaller than 70% indicates a pathological reflex corresponding qualitatively to a partial, weak or absent visual suppression. The study is based on 149 examinations realised in 12 healthy subjects and 137 patients. The patients are classified into 4 groups: a) 59 patients with peripheral vestibular lesions (Meniere's diseases 21, vestibular neuronitis 15, cupulolithiasis 16, ototoxicity 7), b) 67 patients with central lesions of the cerebellum and the brainstem (multiple sclerosis 23, infratentorial tumors 14, vascular brainstem lesions 14, degenerative diseases of the central nervous system 16), c) 6 patients with supratentorial central lesions (hemispheric vascular lesions 4, supratentorial tumors 2), d) 5 patients with congenital nystagmus. All healthy subjects and all patients with peripheral vestibular lesions have a total or subtotal visual suppression corresponding to computed rates greater than 70% (mean: 86.7% and 83.1%). In cerebellar and brainstem lesions about half the patients (56.8%) present a partial, weak or absent visual suppression corresponding to computed rates inferior to 70% (mean: 52.7%). In supratentorial disorders the visual suppression is total or subtotal with computed rates superior to 70% (mean: 79.2%). By patients with congenital nystagmus the visual suppression is uniformly pathological with computed rates inferior to 70% (mean: 19.2%). The results of the visual suppression test are concordant with those of smooth pursuit in 92.6% of cases and with those of optokinetic nystagmus in 89.3% of cases. This study confirms that the visual suppression test is a useful examination to detect disorders of the cerebellum and brainstem. PMID- 1588904 TI - HIV prevention in the U.S. correctional system, 1991. AB - During 1990, an estimated 4,350,000 adults--2.4% of the total U.S. adult population--were under correctional supervision* in the United States, a 75% increase since 1983 (1). From 1983 through 1989, the number of juveniles (aged 10 17 years) in custody increased 25%, from 80,091 to 99,846 (U.S. Department of Justice, personal communication, 1992). By November 1990, 4519 cases of acquired immunodeficiency syndrome (AIDS) had been reported among inmates in federal and 45 state prisons, and 2466 cases had been reported by 25 city/county jail systems (U.S. Department of Justice, unpublished data, 1991); these totals include both cases of AIDS reported among persons before their incarceration as well as those reported by prison systems. This report characterizes efforts to prevent human immunodeficiency virus (HIV) transmission within correctional systems. PMID- 1588905 TI - The lysozyme locus in Drosophila melanogaster: different genes are expressed in midgut and salivary glands. AB - As part of a study of the genes involved in antibacterial defense in Drosophila melanogaster, we have isolated genomic clones harboring a family of chicken-type lysozyme genes, using a lepidopteran lysozyme cDNA as probe. The locus was mapped to the cytological location 61F1-4 on the third chromosome and two of the genes at this locus, LysD and LysP, were analyzed in detail. In contrast to the bacteria-induced lysozymes in the hemolymph of many insects, the transcription levels of both Drosophila genes decrease after bacterial injections into the hemocoel. Apparently, these gene products, like the specifically adapted lysozymes in mammalian foregut fermenters, have been recruited for the digestion of bacteria present in fermenting food. The LysD gene is expressed in an anterior section of the midgut during all feeding stages of development in both larvae and adults. The LysP gene is only active in the adult where it is expressed in the salivary glands. The transcription units for both genes are very compact and they lack introns. Lysozyme D is unusual in that it is predicted to have an acidic isoelectric point whereas lysozyme P appears to be a typical basic lysozyme. PMID- 1588906 TI - Identification of the structural genes for N-acetylmuramoyl-L-alanine amidase and its modifier in Bacillus subtilis 168: inactivation of these genes by insertional mutagenesis has no effect on growth or cell separation. AB - The region of the Bacillus subtilis 168 chromosome that contains the structural genes for the major vegetative cell autolysin, (N-acetyl-muramoyl-L-alanine amidase), and its modifier protein has been cloned. Insertional mutagenesis with integrative plasmids carrying small DNA fragments from this region has revealed that both genes are located on a 4 kb fragment; they are organised in one transcription unit, the modifier being transcribed first. Studies of derivatives in which either the amidase or the modifier or both proteins are inactivated have revealed that amidase-deficient strains are not affected in growth, cell separation, transformability or sporulation. Observed phenotypic differences were altered kinetics of, cell wall turn-over and a reduced rate of, autolysis of native cell wall preparations. A residual amidase activity, about 3% of that of the wild-type strain, was found in strains devoid of the major amidase. A new, distinct cell wall-bound protein, designated CWBP49', with the same molecular weight as the amidase, was identified in mutants devoid of the latter enzyme. PMID- 1588907 TI - Molecular cloning and analysis of Schizosaccharomyces pombe rad9, a gene involved in DNA repair and mutagenesis. AB - The mutant allele rad9-192 renders Schizosaccharomyces pombe cells sensitive to ionizing radiation and UV light. We have isolated from a S. pombe genomic DNA library a unique recombinant plasmid that is capable of restoring wild-type levels of radioresistance to a rad9-192-containing cell population. Plasmid integration studies using the cloned DNA, coupled with mating and tetrad analyses, indicate that this isolated DNA contains the wild-type rad9 gene. We inactivated the repair function of the cloned fragment by a single insertion of the S. pombe ura4 gene. This nonfunctional fragment was used to create a viable disruption mutant, thus demonstrating that the rad9 gene does not encode an essential cellular function. In addition, the rad9-192 mutant population is as radiosensitive as the disruption mutant, indicating that rad9 gene function is severely if not totally inhibited by the molecular defect responsible for the rad9-192 phenotype. DNA sequence analysis of rad9 reveals an open reading frame of 1,278 bp, interrupted by three introns 53 bp, 57 bp, and 56 bp long, respectively, and ending in the termination codon TAG. This gene is capable of encoding a protein of 426 amino acids, with a corresponding calculated molecular weight of 47,464 daltons. No significant homology was detected between the rad9 gene or its deduced protein sequence and sequences previously entered into DNA and protein sequence data banks. PMID- 1588909 TI - Isolation and phenotypic analysis of conditional-lethal, linker-insertion mutations in the gene encoding the largest subunit of RNA polymerase II in Saccharomyces cerevisiae. AB - Linker-insertion mutagenesis was used to isolate mutations in the Saccharomyces cerevisiae gene encoding the largest subunit of RNA polymerase II (RPO21, also called RPB1). The mutant rpo21 alleles carried on a plamid were introduced into a haploid yeast strain that conditionally expresses RPO21 from the inducible promoter pGAL10. Growth of this strain on medium containing glucose is sustained only if the plasmid-borne rpo21 allele encodes a functional protein. Of nineteen linker-insertion alleles tested, five (rpo21-4 to -8) were found that impose a temperature-sensitive (ts) lethal phenotype on yeast cells. Four of these five ts alleles encode mutant proteins in which the site of insertion lies near one of the regions of the largest subunit that have been conserved during evolution. Two of the ts mutants (rpo21-4 and rpo21-7) display pleiotropic phenotypes, including an auxotrophy for inositol and a decreased proliferation rate at the permissive temperature. The functional relationship between RPO21 and RPO26, the gene encoding the 17.9 kDa subunit shared by RNA polymerases I, II, and III was investigated by determining the ability of increased dosage of RPO26 to suppress the ts phenotype imposed by rpo21-4 to -8. Suppression of the ts defect was specific for the rpo21-4 allele and was accompanied by co-suppression of the inositol auxotrophy. These results suggest that mutations in the largest subunit of RNA polymerase II can have profound effects on the expression of specific subsets of genes, such as those involved in the metabolism of inositol. In the rpo21-4 mutant, these pleiotropic phenotypes can be attributed to a defective interaction between the largest subunit and the RPO26 subunit of RNA polymerase II. PMID- 1588908 TI - Point mutations in two conserved glycine residues within the integral membrane protein FhuB affect iron(III) hydroxamate transport. AB - A region of substantial homology, comprising 32 amino acids around a highly conserved glycine residue, is located near the C-terminal ends of the hydrophobic Fhu, Fec, Fep, Fat, and Btu transport proteins involved in the uptake of ferrisiderophores and vitamin B12 into Escherichia coli and Vibrio anguillarum. Furthermore, a region similar in location and sequence containing an invariant glycine at an equivalent position was identified in the hydrophobic component of all other periplasmic binding protein-dependent (PBT) systems. In the FhuB protein, which is twice the size of the other PBT-related inner membrane proteins and which displays an internal homology, two conserved glycine residues are present. Alteration of Gly at positions 226 and 559 to Ala, Val, or Glu reduced iron(III) hydroxamate uptake, suggesting that this homologous region may play a general role in the mechanism of PBT-dependent transport. PMID- 1588910 TI - Regulation of the Bacillus subtilis W23 xylose utilization operon: interaction of the Xyl repressor with the xyl operator and the inducer xylose. AB - A crude protein extract of Bacillus subtilis W23 contains a sequence-specific DNA binding activity for the xyl operator as detected by the gel mobility shift assay. A xylR determinant encoded on a multicopy plasmid leads to increased expression of this binding activity. In situ footprinting analysis of the protein DNA complex in a polyacrylamide gel shows that the xyl operator is sequence specifically bound and protected from cleavage by copper-phenanthroline at 26 phosphodiester bonds on each strand. Quantitative competition assays for repressor binding reveal that a 25 bp synthetic xyl operator cloned into a polylinker is bound with the same affinity as the operator in the wild-type xyl regulatory region. This confirms that no additional sites in the wild-type sequence contribute to repressor binding. The xyl operator consists of ten palindromic base pairs flanking five central non-palindromic base pairs. A mutational analysis shows that the sequence of the central base pairs contributes to recognition by the repressor protein and that the spacing of the palindromic elements is crucial for repressor binding. An operator half site is not bound by the repressor. In vivo and in vitro induction studies suggest that, of several structurally similar sugars, xylose is the only molecular inducer of the Xyl repressor. PMID- 1588911 TI - Cloning of the mating-type gene MATA of the yeast Yarrowia lipolytica. AB - The mating type gene MATA of the dimorphic yeast Yarrowia lipolytica was cloned. The strategy used was based on the presumed function of this gene in the induction of sporulation. A diploid strain homozygous for the mating type B was transformed with an integrative gene bank from an A wild-type strain. A sporulating transformant was isolated, which contained a plasmid with an 11.6 kb insert. This sequence was rescued from the chromosomal DNA of the transformant and deletion mapping was performed to localize the MAT insert. The MAT gene conferred both sporulating and non-mating phenotypes on a B/B diploid. A LEU2 sequence targeted to this locus segregated like a mating type-linked gene. The A strain did not contain silent copies of the MAT gene. PMID- 1588912 TI - Construction of an Escherichia coli K-12 strain deleted for manganese and iron superoxide dismutase genes and its use in cloning the iron superoxide dismutase gene of Legionella pneumophila. AB - An Escherichia coli K-12 strain deleted for sodA and sodB (manganese and iron superoxide dismutases) was constructed and characterized by Southern blotting, enzyme assays, and physiological analyses. The sod deletion strain was used to clone the iron superoxide dismutase gene of Legionella pneumophila by complementation to paraquat resistance. PMID- 1588913 TI - Expression and regulation of a dnaA homologue isolated from Pseudomonas putida. AB - A gene homologous to the Escherichia coli dnaA gene was isolated from Pseudomonas putida and its transcription was investigated in E. coli as well as in P. putida. In both species the P. putida dnaA gene is transcribed from two promoters, one of which shows strong homology to promoters recognized by the sigma 54 factor found in both bacteria. In E. coli transcription of the P. putida dnaA gene can be repressed by overproduction of E. coli DnaA protein, presumably due to the presence of several DnaA-box-like sequences found in the promoter region. Likewise the P. putida DnaA protein is able to regulate expression of the E. coli dnaA gene but we failed to demonstrate autoregulation of the P. putida dnaA gene. A point mutation was introduced into the P. putida dnaA gene, equivalent to the ATP binding site mutation present in E. coli dnaA5 and dnaA46 mutants, and this alteration abolished the ability of the protein to repress the expression of the E. coli dnaA gene. These results indicate that DnaA proteins from other species than E. coli have maintained the ability to recognize the DnaA box sequence and that the conservation between the DnaA proteins reflects functionally similar domains. PMID- 1588914 TI - Five novel elements involved in the regulation of mitosis in fission yeast. AB - Five new elements of the mitotic control in the fission yeast Schizosaccharomyces pombe were isolated from gene libraries as multicopy suppressors of the conditional lethal phenotype of win1-1 wee1ts cdc25ts triple mutant strains. These genes were designated wis1(+)-wis5+ for win suppressing, and do not correspond to win1+ or any of the previously characterised mitotic control genes. None of the wis genes is capable of suppressing the cdc phenotype of cdc25ts strains, suggesting that their effect is not simply to reverse the effect of loss of cdc25 function. wis1+ has been previously reported to encode a putative serine/threonine protein kinase that acts as a dosage-dependent inducer of mitosis. wis4+ appears to be a specific suppressor of the win1-1 mutation. wis2+ and wis3+ are capable of suppressing a wide range of cdc phenotypes arising from the combination of various mutations with wee1ts and cdc25ts, suggesting that the wis2+ and wis3+ products may interact with elements central to the mitotic control. PMID- 1588915 TI - The structure and regulation of homeologous tobacco endochitinase genes of Nicotiana sylvestris and N. tomentosiformis origin. AB - The fungicidal class I chitinases are believed to be important in the induced defense response of plants. We isolated and partially characterized genomic clones representing two members, CHN14 and CHN50, of the gene subfamily encoding these enzymes in Nicotiana tabacum L. cv. Havana 425. The coding sequences of genes CHN14, CHN50, and CHN48, which was cloned earlier, are identical at 79-95% of the positions. Tobacco is an amphidiploid species derived from ancestors most closely related to the present-day species N. sylvestris and N. tomentosiformis. Southern analysis of genomic DNA, comparison of deduced amino acid sequences, and partial sequencing of the purified enzymes suggest that the gene pairs CHN48/CHN50 and CHN14/CHN14' are homeologues. Gene CHN48, which encodes chitinase A (Mr ca. 34 kDa), and gene CHN14 are derived from N. tomentosiformis; whereas gene CHN50, which encodes chitinase B (Mr ca. 32 kDa), and gene CHN14' are derived from N. sylvestris. Class I chitinases are induced in leaves of plants treated with ethylene or infected with the fungal pathogen Cercospora nicotianae and in cultured cells transferred to medium without added auxin and cytokinin. RNase protection assays show that under these conditions transcripts encoded by the homeologues CHN48 and CHN50 account for greater than 90% of the total chitinase mRNA. The less abundant transcript, CHN48, consistently showed a greater degree of induction than CHN50. Expression of the homeologues CHN14 and CHN14' represented less than 10% of the total chitinase mRNA. They showed a pattern of hormonal regulation similar to CHN48 and CHN50, but transcripts of these genes were not detected in leaves infected with C. nicotianae. Therefore the two sets of homeologues are regulated in the same way by hormones and respond differently to infection by a pathogen. PMID- 1588916 TI - The Salmonella typhimurium RecJ function permits growth of P22 abc phage on recBCD+ hosts. AB - We describe recJ mutants of Salmonella typhimurium. The recJ gene maps between sufD and serA (min 62) and is transcribed counterclockwise. Unlike recJ mutants of Escherichia coli, recJ strains of S. typhimurium are sensitive to irradiation with UV light. This sensitivity is equivalent to or greater that that displayed by recBCD mutant strains. The residual ability of phage P22 abc (anti-recBCD) mutants to form plaques on recBCD+ strains is eliminated in recJ hosts. Thus host RecJ function appears to substitute for the anti-RecBCD functions of phage P22 and may serve to limit RecBCD activity. PMID- 1588917 TI - Evolution of the alcohol dehydrogenase (ADH) genes in yeast: characterization of a fourth ADH in Kluyveromyces lactis. AB - Three alcohol dehydrogenase (ADH) genes have recently been characterized in the yeast Kluyveromyces lactis. We report on a fourth ADH in K. lactis (KADH II: KADH2* gene) which is highly similar to other ADHs in K. lactis and Saccharomyces cerevisiae. KADH II appears to be a cytoplasmic enzyme, and after expression of KADH2 in S. cerevisiae enzyme activity comigrated with a K. lactis ADH present in cells grown in glucose or in ethanol. KADH I was also expressed in S. cerevisiae and it comigrated with a major ADH species expressed under glucose growth conditions in K. lactis. The substrate specificities for KADH I and KADH II were shown to be more similar to that of SADH II than to SADH I. SADH I cannot efficiently utilize long chain alcohols, in contrast to other cytoplasmic yeast ADHs, presumably because of the presence of a methionine (residue 271) in its substrate binding cleft. A comparison of the DNA sequences of ADHs among K. lactis, S. cerevisiae and Schizosaccharomyces pombe suggests that the ancestral yeast species contained one cytoplasmic ADH. After divergence from S. pombe, the ADH in the ancestor to K. lactis and S. cerevisiae was duplicated, and one ADH became localized to the mitochondrion, presumably for the oxidative use of ethanol. Following the speciation of S. cerevisiae and K. lactis, the gene encoding the cytoplasmic ADH in S. cerevisiae duplicated, which resulted in the development of the SADH II protein as the primary oxidative enzyme in place of SADH III. In contrast, the K. lactis mitochondrial ADH duplicated to give rise to the highly expressed KADH3 and KADH4 genes, both of which may still play primary roles in oxidative metabolism. These data suggest that K. lactis and S. cerevisiae use different compartments for their metabolism of ethanol. Our results also indicate that the complex regulatory circuits controlling the glucose-repressible SADH2 in S. cerevisiae are a recent acquisition from regulatory networks used for the control of genes other than SADH2. PMID- 1588918 TI - Expression of luciferase genes from different origins in Bacillus subtilis. AB - A group of vectors for luciferase expression in Bacillus subtilis was constructed. So far, only bacterial luciferases have been expressed in Bacillus, but in this study we wanted also to express genes encoding eukaryotic luciferases to perform direct comparisons of the light levels produced by the two different systems in B. subtilis. The vectors constructed can replicate both in Escherichia coli and B. subtilis, and the luciferase expression is strictly regulated due to the dual plasmid system used. Nearly a 100-fold increase in light production compared to previous results was achieved when genes encoding bacterial luciferase were inserted into the constructs and transformed into B. subtilis. An additional tenfold increase in light production was obtained when luciferase genes from the North American firefly (Photinus pyralis) or a click beetle (Pyrophorus plagiophtalamus) were introduced in a similar fashion into B. subtilis. Measurement of the light emission was performed without disruption of bacterial cells in a real-time manner, which is a common feature when working with all of these constructions. Structures of the shuttle vector constructs and results from light emission measurements are presented. PMID- 1588919 TI - DNA-binding properties of a distamycin-ellipticine hybrid molecule. AB - We have synthesized a distamycin-ellipticine hybrid compound and investigated its interaction with DNA, using various optical and gel electrophoresis techniques. Binding of the hybrid to DNA is evidenced by spectral shifts, fluorescence quenching, and induced linear dichroism. Absorbance measurements have been used to generate Scatchard plots, which reveal that the interaction cannot be described adequately in terms of a single binding mode, probably because of simultaneous intercalation and minor groove binding of the ligand. Competition with added distamycin has been used to verify involvement of the N-methyl-pyrrole portion of the hybrid molecule in the binding reaction. From electric linear dichroism experiments, it is estimated that the orientation of the DNA-bound ellipticine chromophore in the hybrid differs by about 10 degrees from the orientation of the equivalent chromophore lacking a distamycin tail. Topoisomerase assays establish that binding of the hybrid unwinds the DNA helix by a minimum of 11 degrees, which is consistent with intercalation but notably smaller than the unwinding angle of ellipticine. In footprinting experiments, it is found that the AT- and GC-specificity of distamycin and ellipticine, respectively, appear to be merged in the binding of the hybrid, which produces a pattern of protection distinct from the characteristic patterns for either of the parent compounds. The hybrid is an extremely effective inhibitor of cutting by DNase I. PMID- 1588920 TI - Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens. AB - Rat and human lung microsomal cytochrome P-450 (P-450) enzymes have been characterized with regard to their catalytic activities towards several xenobiotic chemicals, including procarcinogens, in different microsomal preparations. Rat lung microsomal P-450s were more active than the human P-450s in catalyzing most of the monooxygenation reactions. Human lung microsomal P-450 was solubilized and purified. Human lung microsomes contain approximately 10 pmol of P-450/mg of protein, on the basis of Fe2+.CO versus Fe2+ difference spectra of the eluates obtained from an octylamino-agarose column. The partially purified P 450 preparations from two human lung microsomal samples showed high activities for the conversion of both (+)- and (-)-isomers of 7,8-dihydroxy-7,8 dihydrobenzo(a)pyrene to genotoxic products. After DEAE-cellulose column chromatography, a partially purified P-450 fraction containing polypeptides of Mr 52,000 and 58,000 was obtained from the early fraction of the octylamino-agarose column eluate, and an electrophoretically homogeneous protein having a molecular weight of approximately 52,000 was recovered from a latter fraction. The amino terminal amino acid sequences of the two peptides in the earlier fraction were determined; neither polypeptide appears to resemble any known P-450 protein. The protein from the latter octylamino-agarose fraction was immunoreactive with anti rat P-450 1A2 and anti-human P-450 1A2 but not with antibodies raised against other P-450 enzymes or autoimmune antibodies that specifically recognize human P 450 1A2. A tryptic peptide was isolated from the preparation, and the amino acid sequence matched that of human P-450 1A1 perfectly (residues 31-48) but not that of human P-450 1A2. All of nine human lung microsomal samples examined contained proteins that were immunoreactive with rabbit anti-rat P-450 1A2 and catalyzed the activation of 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene. The activities could be inhibited by rabbit anti-rat P-450 1A2 and, to a lesser extent, by anti-rat P 450 1A1. The addition of 7,8-benzoflavone caused inhibition or stimulation, depending upon the particular human lung microsomal preparation. Thus, this work clearly shows that human lung microsomes contain at least two major P-450 enzymes; human P-450 1A1 is present in lungs and can actually catalyze the activation of environmental procarcinogens, including polycyclic aromatic hydrocarbons. PMID- 1588921 TI - Human liver dehydroepiandrosterone sulfotransferase: molecular cloning and expression of cDNA. AB - Sulfation is an important pathway in the metabolism of many hormones and drugs. Human liver contains at least three well characterized sulfotransferase (ST) enzymes, i.e., dehydroepiandrosterone (DHEA) ST and two forms of phenol sulfotransferase (PST). Our goal was to purify, to obtain partial amino acid sequence for, and to clone and express cDNA for human liver DHEA ST. Polymerase chain reaction primers were designed on the basis of homology among rat liver hydroxysteroid ST, rat liver PST, and bovine estrogen ST. These primers amplified a unique sequence from human liver cDNA, and this polymerase chain reaction product was used to screen a human liver cDNA library. Two clones were isolated that contained identical open reading frames, of 855 nucleotides, that encoded a protein of 285 amino acids. The deduced amino acid sequence of the encoded protein included two separate 27- and 23-amino acid sequences that were identical to those obtained by microsequencing of proteolytic fragments from purified human liver DHEA ST. Translation, in a rabbit reticulocyte lysate system, of mRNA transcribed in vitro from the two cDNA clones resulted in a 35-kDa translation product that comigrated with purified human liver DHEA ST during sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This translation product also catalyzed the sulfation of DHEA but not the sulfation of model substrates for the two forms of PST found in human liver. The two cDNA clones were also used to create expression constructs with the eukaryotic expression vector P91023(B), and these constructs were used to transfect COS-1 cells. The transfected cells expressed a high level of DHEA ST activity, and this enzyme activity displayed a pattern of inhibition by the ST inhibitor 2,6-dichloro-4-nitrophenol identical to that of human liver DHEA ST. Cloning of cDNA for this important human sulfate conjugating enzyme will enhance understanding of the relationship between DHEA ST and other human liver STs, as well as ST enzymes in other species. PMID- 1588922 TI - Characterization of a 5-lipoxygenase-activating protein binding assay: correlation of affinity for 5-lipoxygenase-activating protein with leukotriene synthesis inhibition. AB - A binding assay has been developed to measure the affinity of leukotriene synthesis inhibitors for 5-lipoxygenase-activating protein (FLAP), using human leukocyte membranes as the source of FLAP and a radioiodinated leukotriene synthesis inhibitor, 125I-L-691,831, as ligand. Linearity of specific binding of radiolabeled ligand was demonstrated with increasing protein and ligand concentrations. Saturation analysis of radioligand binding showed a Kd of 6 nM and a Bmax that, depending on the membrane preparation, varied between 8 and 53 pmol/mg of protein. An excellent correlation was shown between affinity for FLAP in the binding assay and inhibition of leukotriene synthesis in human polymorphonuclear leukocytes for compounds from two structurally distinct classes, namely indoles and quinolines. A large number of membrane-active compounds did not compete with 125I-L-691,831 binding to FLAP. In addition, direct 5-lipoxygenase inhibitors and a selection of eicosanoids were unable to compete for FLAP binding. This study validates a selective binding assay for leukotriene synthesis inhibitors whose protein target is FLAP. PMID- 1588923 TI - Forskolin acts as a noncompetitive inhibitor of nicotinic acetylcholine receptors. AB - Bath application of micromolar concentrations of forskolin to Xenopus oocytes that express either Torpedo electroplax or mouse muscle nicotinic acetylcholine (ACh) receptors leads to a reduction in the size of the ACh-elicited currents. This inhibition is concentration dependent and rapidly reversible, with full onset and recovery occurring within the exchange time of the recording chamber. Torpedo and mouse ACh receptors exhibit differential sensitivity to forskolin, with the Torpedo receptor showing higher affinity than the mouse receptor, with Ki values of 6.5 microM and 22 microM, respectively. The affinity for forskolin increases with ACh concentration, which rules out the possibility that forskolin acts as a competitive inhibitor. Single-channel analysis using excised patches shows that forskolin has no effect on either the single-channel amplitude or mean open time but, instead, reduces the number of channel openings per unit time, suggesting that forskolin either is a very slow channel blocker or alters receptor gating such that a fraction of the channels enter a state from which they are no longer available to open. Finally, through the use of a series of mouse-Torpedo hybrid ACh receptors, it is shown that the structural features responsible for the observed species difference in the affinity of ACh receptors for forskolin, and thus at least part of the binding site, are located on the gamma subunit. PMID- 1588924 TI - Ambenonium is a rapidly reversible noncovalent inhibitor of acetylcholinesterase, with one of the highest known affinities. AB - Steady state patterns of inhibition of purified human erythrocyte acetylcholinesterase by three inhibitors were analyzed. Edrophonium acted essentially as a competitive inhibitor, whereas tacrine and ambenonium gave mixed competitive and uncompetitive inhibition with acetylthiocholine as substrate. Inhibition constants for the competitive components were 470 microM for edrophonium, 65 microM for tacrine, and 0.12 nM for ambenonium. The extremely high affinity of ambenonium permitted analysis of the rates of approach to steady state inhibition. These rates were characterized by a single exponential time course with rate constants, kexp, that showed a linear dependence when plotted against ambenonium concentration, at fixed substrate concentration. The intercepts of these plots were independent of the substrate concentration and indicated an ambenonium dissociation rate constant of 0.013 +/- 0.002 sec-1. The slope of the plot at the lowest substrate concentration approximated the ambenonium bimolecular or association rate constant and gave a value of 5.2 +/- 0.6 x 10(7) M-1 sec-1. Three models were examined to account for the nearly linear dependence of the slopes of these plots on the substrate concentration. These models indicated that ambenonium and acetylthiocholine competed for a peripheral anionic site in the acetyl-enzyme intermediate formed during substrate hydrolysis. The apparent equilibrium dissociation constant of acetylthiocholine for this peripheral site (1.2-1.4 mM) was significantly different from that calculated from substrate inhibition data (20.1 +/- 2.8 mM). We propose that acetylthiocholine can interact with the acetyl-enzyme both at the peripheral site and at the active site but that only the latter interaction inhibits substrate hydrolysis. PMID- 1588925 TI - Membrane permeation characteristics of 5'-modified thymidine analogs. AB - The membrane permeation characteristics of 5'-deoxythymidine (5'-ddThd) and 5' azido-5'-deoxythymidine (5'-N3-5'-ddThd) were investigated in human erythrocytes, with an inhibitor-stop assay, at 20 degrees. Uptake of both nucleoside analogs occurred without metabolism, was nonconcentrative, and was partially inhibited by nucleosides or inhibitors of nucleoside transport at micromolar permeant concentrations. At higher permeant concentrations (greater than 1.0 mM), the influx rate of each analog was linearly dependent on concentration and insensitive to inhibition by nucleosides, inhibitors of nucleoside transport, and nucleobases. Kinetic analyses using nonlinear regression revealed that a saturable component of 5'-ddThd influx (Km = 200 microM) was competitively inhibited by thymidine (dThd) (Ki = 86 microM) or 5-iodo-2'-deoxyuridine (Ki = 84 microM). Similarly, a saturable component of 5'-N3-5'-ddThd influx (Km = 220 microM) was competitively inhibited by 2-chloroadenosine (Ki = 18 microM). The Ki values for these nucleoside inhibitors were similar to their reported Km values as permeants of the nucleoside transporter. Both 5'-ddThd and 5'-N3-5'-ddThd competitively inhibited the influx of dThd (Km = 60 microM), with similar Ki values (150 and 200 microM, respectively). We conclude that these two 5'-modified dThd analogs enter human erythrocytes both by nonfacilitated diffusion and by the nucleoside transporter. The absence of the 5'-hydroxyl group of dThd (5'-ddThd) resulted in a large increase in the octanol/buffer partition coefficient, in an ability to permeate human erythrocytes by nonfacilitated diffusion, and in a 3 fold diminished binding to the nucleoside transporter. The 5'-azido group (5'-N3 5'-ddThd) resulted in an additional 1.4-fold increase in the octanol/buffer partition coefficient and in a 2-fold increase in the rate of nonfacilitated diffusion. PMID- 1588926 TI - Role of desolvation energy in the nonfacilitated membrane permeability of dideoxyribose analogs of thymidine. AB - The ability of thymidine and four dideoxyribose analogs of thymidine to cross phase barriers, such as those encountered at the exo and endo faces of a membrane, has been studied in a two-phase water/chloroform system. The rate constants for entering, ka, and leaving, kb, the organic phase and the partition coefficient, Kp (ka/kb), were determined for each compound. The values of Kp were found to be proportional to the values of the rate constants for nonfacilitated diffusion, c, into human erythrocytes reported in the preceding paper [Mol. Pharmacol. 41:950-956 (1992)]. This linear relationship suggests that, in accord with the solubility-diffusion model of nonmediated membrane permeation, movement of the thymidine analogs across the potential energy barriers at the membrane interfaces is fast, relative to the rate of transbilayer diffusion. Because the compounds have similar molecular volumes and would, therefore, have similar rates of transbilayer diffusion, the differences in c reflect the differences in the distribution of the compounds across the interfaces, i.e., the Kp values. The magnitudes of the Kp values are dependent not only on the pi value of each substituent on the dideoxyribose ring but also on the position of the substituent. Analogs having a hydroxyl group in the 5'-position have a higher Kp and a higher c than the corresponding analogs with the hydroxyl group in the 3' position. This increased lipophilicity is attributed to a decrease in desolvation energy, resulting from the ability of the 5'-hydroxyl analogs to assume a syn configuration in which a bifurcated, intramolecular, hydrogen bond can be formed to the O-4' and the C-2 carbonyl groups. PMID- 1588927 TI - Effects of L-histidine on hydrogen peroxide-induced DNA damage and cytotoxicity in cultured mammalian cells. AB - L-Histidine markedly increased the growth- and DNA synthesis-inhibitory effects elicited by hydrogen peroxide in cultured Chinese hamster ovary cells. DNA single strand breakage was also higher in the presence of the amino acid and, in addition, these breaks were characterized by a slower rate of repair, compared with that of the breaks generated by the oxidant alone. In the presence of L histidine, hydrogen peroxide also produced DNA double-strand breakage, a lesion that cannot be detected in cells treated with even exceedingly high concentrations of the oxidant alone. Data reported herein suggest that the L histidine-mediated increase of the cytotoxic response of cultured Chinese hamster ovary cells to hydrogen peroxide may be at least partially dependent on the formation of DNA double-strand breaks. PMID- 1588928 TI - Human liver microsomal N-hydroxylation of dapsone by cytochrome P-4503A4. AB - One of the major routes of elimination of dapsone (4,4'-diaminodiphenylsulfone) is by N-oxidation, to produce a hydroxylamine metabolite. The specific form of cytochrome P-450 (P-450) involved in this oxidation reaction was examined in human liver microsomal preparations previously characterized with respect to their content of several known P-450 enzymes. Among five preparations, the rank order of activity for dapsone hydroxylamine formation was most well correlated with the immunochemically determined level of P-4503A4 (r = 0.94, p less than 0.03). Moreover, inhibition of microsomal oxidation was observed with antibodies specific to P-4503A, with a maximum reduction of greater than 90%, but was not produced by antibodies specific to P-4501A2, P-4502CMP, or P-4502E1. Prior incubation of microsomes with gestodene (100 microM) or troleandomycin (20 microM), known selective mechanism-based inhibitors of P-4503A enzymes (in the presence of NADPH), led to 75% and 40% reductions in catalytic activity, respectively. In contrast, preincubation with increasing concentrations of alpha naphthoflavone, a known activator of P-4503A4, increased dapsone N-hydroxylation in a concentration-dependent manner, with 5-fold activation being observed at 50 microM alpha-naphthoflavone. Finally, P-4503A4 isolated from human liver microsomes and cDNA-expressed P-4503A4 (in yeast) were both able to catalyze dapsone N-hydroxylation, with the latter preparation exhibiting a 3-fold activation in the presence of 100 microM alpha-naphthoflavone. Collectively, these findings demonstrate that N-oxidation of dapsone in human liver is predominantly mediated by P-4503A4, and they suggest that quantitative measurement of this metabolic pathway in vivo might serve as an index of the activity of this enzyme. PMID- 1588929 TI - Imprinting of hepatic microsomal cytochrome P-450 enzyme activities and cytochrome P-450IIC11 by peripubertal administration of testosterone in female rats. AB - The influence of peripubertal exposure to physiological doses of testosterone on the adult androgen responsiveness of hepatic microsomal cytochrome P-450 was investigated. Male and female Sprague-Dawley rats were sham-operated or gonadectomized before puberty, at 25 days of age. They were injected subcutaneously with testosterone enanthate (5 mumol/kg/day) during the pubertal time period, on days 35-49. Responsiveness to this same dose of testosterone was tested by administering the compound during adulthood, on days 81-89. The females provided a model that had not been exposed to neonatal androgen imprinting, in contrast to the males. Testosterone 2 alpha-hydroxylase activity and cytochrome P 450IIC11, which are normally expressed only in adult males, were expressed in the gonadectomized females administered testosterone during puberty with no further exposure to the hormone for the next 40 days. The levels found were similar to those in the gonadectomized male group. When the combined pubertal and adult testosterone regimen was used, a synergistic effect was produced; the 2 alpha hydroxylase activity reached control male levels in both gonadectomized and sham operated females and, in addition, cytochrome P-450IIC11 attained control male levels in the gonadectomized females. Testosterone 6 beta-hydroxylase and erythromycin N-demethylase activities were used as indicators of the cytochrome P 450IIIA subfamily. These activities were significantly increased only in the females treated with testosterone during both the pubertal and adult periods, reaching control male levels of 6 beta-hydroxylation. A similar effect, but in the opposite direction, was found with testosterone 7 alpha-hydroxylase, an enzyme activity indicative of cytochrome P-450IIA1. A decrease in this enzyme was produced in the females administered testosterone during both time periods, resulting in levels equivalent to those found in control males. In general, a highly significant interaction was found between the pubertal and adult treatment periods for the females, indicating a chronic effect of the pubertal exposure. The experiments with castrated males did not result in synergistic interactions, although there was some evidence of an additive effect. The results of this study support the hypothesis that the peripubertal period is a time during which testosterone imprinting of both increased basal levels and adult androgen responsiveness of some hepatic cytochrome P-450 enzymes can occur in the female rat. PMID- 1588930 TI - Free radicals in myocardial injury and atherosclerosis. PMID- 1588931 TI - Oxygen free radicals in essential hypertension. AB - Membrane abnormalities in essential hypertensives (EH) are well known. The respiratory burst enzyme, NADPH oxidase is located in the cell membrane of the neutrophil (PMNLs) and its activity is important in generation of oxygen derived free radical (OFR). Recently OFR have been implicated in vascular changes in variety of conditions. An attempt was made to delineate the status of OFR and antioxidants in EH. Ten, age and sex-matched, healthy controls (GpI) and 26 untreated EH (Gp IIA mild-8, Gp IIB Moderate-8, Gp IIC Severe-10) were studied. After clinical examination and basic laboratory evaluation of subjects, neutrophils isolated from their blood were studied. Chemiluminescence (CL) emitted by PMNLs after stimulation was measured (counts/min) in a luminometer and was taken as measure of OFR production and thereby of NADPH oxidase activity. The levels of antioxidants, superoxide dismutase (SOD) and reduced glutathione (GSH), were also estimated. Chemiluminescence was increased significantly (p less than 0.01) in Gp IIC (243.04 +/- 24.9 x 10(3) counts per minute) as compared to Gp IIA (2.80 +/- 1.87), Gp IIB (34.54 +/- 30.24) and Gp I (0.52 +/- 0.15) and SOD was reduced significantly (p less than 0.05) in all EH (Gp IIA 3.9 +/- 0.3 units per mg protein, Gp IIB 3.5 +/- 0.3 and Gp IIC 3.12 +/- 0.3) as compared to controls (4.1 +/- 0.2). Similarly GSH was reduced (p less than 0.05) in EH (Gp IIA 11.2 +/ 1.7 mg per gm protein, Gp IIB 8.5 +/- 1.1 and Gp IIC 6.6 +/- 0.3) as compared to Gp I (13.5 +/- 2.5).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1588932 TI - Dietary supplementation of vitamin E protects heart tissue from exercise-induced oxidant stress. AB - Exhaustive endurance exercise in adult female albino rats (C-Ex) increased the generation of free radicals (R.) in the myocardium, probably through enhanced oxidative mechanisms. Free radical mediated lipid peroxidation measured in the form of tissue MDA content also increased in C-Ex animals, suggesting the exercise-induced oxidative stress in these animals. Dietary supplementation of Vit E, for a period of 60 days significantly increased Vit E incorporation into the serum and myocardium, more so in the myocardium. Vit E supplementation to exercising animals completely abolished the radical production. The protection of Vit E against oxidative stress appears to be not mediated through the improvement of antioxidant mechanisms by enzymes like SOD, catalase and Se-GSH Px. However the non Se-GSH Px, the enzyme involved in the reduction of endoperoxides increased significantly in control and Vit E fed animals in response to exercise. The protection of Vit E against exercise-induced oxidative stress was correlated with its multivarious activities like a) scavenger of free radicals; b) inhibition of lipoxygenases; and c) reduction of peroxides in association with lipoxygenases. These studies indicate that dietary supplementation of Vit E protects the animals from the possible oxidative damages of endurance exercise. PMID- 1588934 TI - Studies on spice principles as antioxidants in the inhibition of lipid peroxidation of rat liver microsomes. AB - Polyunsaturated fatty acids (PUFA) are vulnerable to peroxidative attack. Protecting PUFA from peroxidation is essential to utilize their beneficial effects in health and in preventing disease. The antioxidants vitamin E, t butylhydroxy toluene (BHT) and t-butylhydroxy anisole (BHA) inhibited ascorbate/Fe(2+)-induced lipid peroxidation in rat liver microsomes. In addition, a number of spice principles, for example, curcumin (5-50 microM) from turmeric, eugenol (25-150 microM) from cloves and capsaicin (25-150 microM) from red chillies inhibited lipid peroxidation in a dose-dependent manner. Zingerone from ginger inhibited lipid peroxidation at high concentrations (greater than 150 microM) whereas linalool (coriander), piperine (black pepper) and cuminaldehyde (cumin) had only marginal inhibitory effects even at high concentrations (600 microM). The inhibition of lipid peroxidation by curcumin and eugenol was reversed by adding high concentrations of Fe2+. PMID- 1588933 TI - Interrelation of active oxygen species, membrane damage and altered calcium functions. AB - Incubation of freshly isolated rat liver mitochondria in the presence of oxygen free radical generating hypoxanthine-xanthine oxidase system led to swelling of mitochondria as measured by the change in optical density, which was reversed by the addition of superoxide dismutase. O2- in the presence of CaCl2 enhanced the peroxidative decomposition of mitochondrial membrane lipids along with swelling of the organelle. Free radical generation led to enhancement of monoamine oxidase activity while glutathione peroxidase and cytochrome c oxidase were inhibited. Tert-butyl hydroperoxide (t-BHP) caused mitochondrial swelling through oxidative stress. Incorporation of ruthenium red, which is a Ca2+ transport blocker, during assay abolished peroxidative membrane damage and swelling. Dithiothreitol (DTT) accorded protection against t-BHP induced mitochondrial swelling. The above in vitro data suggest a possible interrelationship of active oxygen species, membrane damage and calcium dynamics. PMID- 1588935 TI - Glutathione homeostasis in brain during reperfusion following bilateral carotid artery occlusion in the rat. AB - Rats were subjected to bilateral carotid artery occlusion for 30 min, followed by reperfusion for varying time periods. The concentration of reduced and oxidized glutathione, glutathione peroxidase and glutathione reductase were determined in whole brain after varying periods of reperfusion. Lipid peroxidation was also assessed by determining the levels of malondialdehyde (MDA) in the brain. Reperfusion for 1 hr following bilateral carotid artery occlusion resulted in significant decrease in total glutathione (GSH) concentration along with small but significant increase in oxidized glutathione (GSSG) levels. After 4 hr of reperfusion, GSH levels recovered, although GSSG levels remained elevated up to 12 hr of reperfusion. Increase in malondialdehyde levels was also detected in the brain up to 12 hr of reperfusion. Glutathione reductase activity remained significantly low up to 144 hr of reperfusion, while glutathione peroxidase activity remained unaffected. These results demonstrate that oxidative stress is generated in the brain during reperfusion following partial ischemia due to bilateral carotid artery occlusion. PMID- 1588936 TI - Nonesterified fatty acids and lipid peroxidation. AB - Oxygen free radicals damage cells through peroxidation of membrane lipids. Gastrointestinal mucosal membranes were found to be resistant to in vitro lipid peroxidation as judged by malonaldehyde and conjugated diene production and arachidonic acid depletion. The factor responsible for this in this membrane was isolated and chemically characterised as the nonesterified fatty acids (NEFA), specifically monounsaturated fatty acid, oleic acid. Authentic fatty acids when tested in vitro using liver microsomes showed similar inhibition. The possible mechanism by which NEFA inhibit peroxidation is through iron chelation and iron fatty acid complex is incapable of inducing peroxidation. Free radicals generated independent of iron was found to induce peroxidation of mucosal membranes. Gastrointestinal mucosal membranes were found to contain unusually large amount of NEFA. Circulating albumin is known to contain NEFA which was found to inhibit iron induced peroxidation whereas fatty acid free albumin did not have any effect. Addition of individual fatty acids to this albumin restored its inhibitory capacity among which monounsaturated fatty acids were more effective. These studies have shown that iron induced lipid peroxidation damage is prevented by the presence of nonesterified fatty acids. PMID- 1588937 TI - Atherosclerosis: the eicosanoid connection. AB - This bird's eye view presents connections between the metabolically short-lived local hormones (collectively known as eicosanoids) and atherosclerotic cardiovascular disease. The discussion will be centered around an overview of coronary atherosclerosis with an emphasis on the sequences involved in the formation of atherosclerotic lesions; structure and historical background of oxygenated fatty acids cyclooxygenase and lipoxygenase products--eicosanoids; the generation of free radicals during the formation of endoperoxides by cyclooxygenase; the involvement of eicosanoids in the atherosclerotic inflammatory process, and finally, the effects of non-steroidal and steroidal anti-inflammatory drugs on the synthesis of eicosanoids and experimental atherosclerosis. Little is known about the exact role of eicosanoids in the genesis of atherosclerosis. PMID- 1588938 TI - Role of oxidized human plasma low density lipoproteins in atherosclerosis: effects on smooth muscle cell proliferation. AB - The effects of oxidized human plasma low density lipoproteins (Ox-LDL) on the proliferation of cultured aortic smooth muscle cells was studied, employing viable cell counting, [3H] thymidine incorporation into DNA, and the release of lactate dehydrogenase (LDH) into the medium. Oxidized LDL (prepared by incubation of LDL with copper sulfate) exerted a concentration-dependent stimulation (2 fold, compared to control) of aortic smooth muscle cell proliferation at low concentrations (0.1 micrograms-10 micrograms/ml medium). On the other hand, at high concentrations (25-200 micrograms/ml), Ox-LDL produced a pronounced decrease in viable cells, a decrease in the incorporation of [3H] thymidine into DNA, and an increase in the release of LDH in the medium. In this report, the previously postulated biological roles of oxidized-LDL in atherosclerosis are discussed in view of these findings. PMID- 1588939 TI - Time-course of cardiac myocyte injury due to oxidative stress. AB - Time course of changes in cell morphology, cation content, lipid peroxidation and high energy phosphates was examined in isolated rat cardiac myocytes exposed to oxygen radicals for 0 to 20 min. Xanthine (2 mM) and xanthine oxidase (10 U/L) mixture was used as a source of oxygen radicals. A significant decrease in the number of rod-shape cells with a concomitant increase in the number of hypercontracted cells was observed within 5 min of exposure to xanthine-xanthine oxidase (x-xo). At 10, 15 and 20 min of exposure to x-xo, there was a time dependent increase in the number of round cells. Lipid peroxide content, as indicated by the thiobarbituric acid reactive material, was significantly and progressively increased between 10 to 20 min of perfusion with x-xo. In myocytes exposed to x-xo, Ca2+ and Na+ were increased by 15% and 45% at 15 min and by 55% and 100% at 20 min respectively. Levels of adenosine tri- and di-phosphates were significantly depressed and that of adenosine mono- phosphate were higher at 20 min. These data support the hypothesis that reactive oxygen intermediates can directly influence myocyte structure and function, but these changes seem to occur more slowly in isolated myocytes than in whole hearts. PMID- 1588940 TI - Strand scission in DNA induced by dietary flavonoids: role of Cu(I) and oxygen free radicals and biological consequences of scission. AB - The naturally occurring flavonoid, quercetin, in the presence of Cu(II) and molecular oxygen caused breakage of calf thymus DNA, supercoiled pBR322 plasmid DNA and single stranded M13 phage DNA. In the case of the plasmid, the product(s) were relaxed circles or a mixture of these and linear molecules depending upon the conditions. For the breakage reaction, Cu(II) could be replaced by Fe(III) but not by other ions tested [Fe(II), Co(II), Ni(II), Mn(II) and Ca(II)]. Structurally related flavonoids, rutin, galangin, apigenin and fisetin were effective or less effective than quercetin in causing DNA breakage. In the case of the quercetin-Cu(II) reaction, Cu(I) was shown to be essential intermediate by using the Cu(I)-sequestering reagent, bathocuproine. By using Job plots we established that, in the absence of DNA, five Cu(II) ions were reduced by one quercetin molecule; in contrast two ions were reduced per quercetin molecule in the DNA breakage reaction. Equally neocuproine inhibited the DNA breakage reaction. The involvement of active oxygen in the reaction was established by the inhibition of DNA breakage by superoxide dismutase, iodide, mannitol, formate and catalase (the inhibition was complete in the last case). The strand scission reaction was shown to account for the biological activity of quercetin as assayed by bacteriophage inactivation. From these data we propose a mechanism for the DNA strand scission reaction of quercetin and related flavonoids. PMID- 1588941 TI - Protective role of ascorbic acid against lipid peroxidation and myocardial injury. AB - Ascorbic acid (AH2) is a potential scavenger of superoxide radical and singlet oxygen. In the guinea pig, marginal AH2 deficiency results in intracellular oxidative damage in the cardiac tissue as evidenced by lipid peroxidation, formation of fluorescent pigment and loss of structural integrity of the microsomal membranes. The oxidative damage does not occur due to lack of enzymatic scavengers of reactive oxygen species such as superoxide dismutase, catalase and glutathione peroxidase. Also, glutathione transferase activity is not decreased in AH2 deficiency. Lipid peroxidation, fluorescent pigment formation and protein modification disappear after AH2 therapy. These results, if extra-polated to human beings, would indicate that chronic subclinical AH2 deficiency may result in progressive oxidative damage which in the long run may lead to permanent degenerative diseases in the heart. PMID- 1588942 TI - Lipid peroxidation during myocardial reperfusion. AB - Reperfusion of heart muscle after prolonged ischaemia is associated with metabolic and functional abnormalities and eventual cell death. Free radical induced lipid peroxidation of cell membranes is thought to be a major mechanism in the evolution of reperfusion damage. The evidences in support for this kind of damage are based on tissue malondialdehyde quantitation by the thiobarbituric acid test (TBA-test). In an attempt to verify this topic we have subjected isolated and Langendorff perfused rabbit hearts to a period of 60 minutes of severe ischaemia plus 30 minutes of reperfusion. At appropriate time points malondialdehyde was determined in the tissue by means of TBA-test and directly by reversed phase, high pressure, liquid chromatography (HPLC). We have found no correlation between the two compared assays. During reperfusion, there was the formation of non-lipid related, malondialdehyde-like, TBA-reactive substance which leads to overestimations of the extent of lipid peroxidation. On the contrary, by direct HPLC quantitation, there was a decrease of tissue malondialdehyde during ischaemia and during the early phases of reperfusion. Our results demonstrate that TBA-test is not a reliable index of malondialdehyde accumulation in organ system. PMID- 1588943 TI - Oxygen free radicals in volume overload heart failure. AB - It has been suggested that oxygen free radicals (OFR) depress the excitation contraction coupling in cardiac muscle. It is possible that a decrease in the cardiac contractility in the failing heart may be due to an increased OFR producing activity of polymorphonuclear (PMN) leukocytes. We studied the OFR producing activity (chemiluminescence) of PMN leukocytes from blood in dogs with heart failure due to chronic volume overload. The animals were divided into two groups: I) normal, (n = 10): II) dogs with mitral insufficiency (MI) of 6 to 9 months duration, (n = 10). Hemodynamic studies were done to establish the presence of heart failure. Blood samples were collected to measure PMN leukocyte chemiluminescence. There was a decrease in the cardiac index and index of myocardial contractility (dp/dt/IIP) and an increase in the left ventricular end diastolic pressure in dogs with MI indicating left ventricular failure. The peak chemiluminescent activity of the PMN leukocytes in blood of dogs with failure was about four folds greater than that in the blood from normal dogs. These results suggest that there may be an increased OFR generation in dogs with volume overload heart failure. The decrease in the myocardial contractility in the failing heart might be due to an increase in the OFR produced by the PMN leukocytes. PMID- 1588944 TI - Occurrence of oxidative stress during myocardial reperfusion. AB - Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may however cause further damage. Myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of this reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and intracellular pool of reduced glutathione. Consequently, reperfusion results in a severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione. An oxygen free radical mediated impairment of mechanical function also occurs during reperfusion of human heart. In fact we observed during surgical reperfusion of coronary artery disease (CAD) patients, a prolonged and sustained release of oxidized glutathione; the degree of oxidative stress was inversely correlated with recovery of mechanical and haemodynamic function. These findings represent the rationale for therapeutic interventions which increase the cellular antioxidant capacities and improve the efficacy of myocardial reperfusion. PMID- 1588945 TI - Free radicals in myocardial injury: experimental and clinical studies. AB - The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium. PMID- 1588946 TI - Oxygen-derived free radicals and hemolysis during open heart surgery. AB - Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH.). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH.. PMID- 1588947 TI - Differences in adaptive stabilization of structures in response to stress and hypoxia relate with the accumulation of hsp70 isoforms. AB - The phenomenon of adaptive stabilization of structures (PhASS) develops during adaptation of the organism to intermittent restraint stress. The PhASS manifests itself in a considerably increased resistance of the heart to a broad spectrum of harmful factors. In the present work, the content of hsp70 and their role in the development of PhASS during adaptation to intermittent restraint stress and to intermittent hypoxia were studied. In adaptation to restraint stress, five hsp70 isoforms with pI ranging from 5.7 to 6.3 were accumulated in the myocardium. The heart simultaneously became strikingly resistant to reperfusion paradox and heat shock. In adaptation to hypoxia, only two hsp70 isoforms with pI about 5.8 were accumulated. The resistance to reperfusion paradox was not increased and the resistance to heat shock was increased only moderately. These data suggest a role of different hsp70 isoforms in the mechanism of PhASS as well as adaptive protection of the heart. PMID- 1588948 TI - Reduced free radical generation during reperfusion of hypothermically arrested hearts. AB - Several studies indicate the presence of hydroxyl radical (OH.) as well as its involvement in the myocardial reperfusion injury. A transition metal-like iron is necessary for the conversion of superoxide anion (O2-) to a highly reactive and cytotoxic hydroxyl radical (OH.). In the present study, we have examined the generation of OH. and free iron in reperfused hearts following either normothermic (37 degrees C) or hypothermic ischemia (5 degrees C). Employing the Langendorff technique, isolated rat hearts were subjected to global ischemia for 30 min at 37 degrees C or 5 degrees C and were then reperfused for 15 min at 37 degrees C. The results of the study suggest that both the OH. generation in myocardium and free iron release into perfusate were significantly lower in hearts made ischemic at 5 degrees C as compared to 37 degrees C. Release of myoglobin and lactic acid dehydrogenase into perfusate also followed a similar pattern. Furthermore, in in vitro studies, chemically generated O2- at 5 degrees C caused a significantly lower rate of oxidation of oxymyoglobin as well as generation of OH. and free iron as compared to 37 degrees C. These results suggest that (1) reperfusion of hypothermic ischemic heart is associated with a reduction in the generation of OH. and cellular damage compared to that of normothermic ischemic heart, and (2) myoglobin, an intracellular protein, is a source of free iron and plays a role in the reperfusion injury mediated by free radicals. PMID- 1588949 TI - The retinoblastoma gene product regulates Sp1-mediated transcription. AB - We have demonstrated that the retinoblastoma gene product (Rb) can positively regulate transcription from the fourth promoter of the insulinlike growth factor II gene. Two copies of a motif (the retinoblastoma control element) similar to that found in the human c-fos, transforming growth factor beta 1, and c-myc promoters are responsible for conferring Rb regulation to the fourth promoter of the insulinlike growth factor II gene. We have shown that the transcription factor Sp1 can bind to and stimulate transcription from the retinoblastoma control element motif. Moreover, by using a GAL4-Sp1 fusion protein, we have directly demonstrated that Rb positively regulates Sp1 transcriptional activity in vivo. These results indicate that Rb can function as a positive regulator of transcription and that Sp1 is one potential target, either directly or indirectly, for transcriptional regulation by Rb. PMID- 1588950 TI - The role and fate of DNA ends for homologous recombination in embryonic stem cells. AB - We have analyzed the gene-targeting frequencies and recombination products generated by a series of vectors which target the hprt locus in embryonic stem cells and found the existence of alternative pathways that depend on the location of the double-strand break within the vector. A double-strand break in the targeting homology was found to increase the targeting frequency compared with a double-strand break at the edge of or outside the target homology; this finding agrees with the double-strand break repair model proposed for Saccharomyces cerevisiae. Although a double-strand break in the homology is important for efficient targeting, observations reported here suggest that the terminal ends are not always directly involved in the initial recombination event. Short terminal heterologous sequences which block the homologous ends of the vector may be incorporated into the target locus. A modification of the double-strand break repair model is described to account for this observation. PMID- 1588951 TI - Point mutations in the Drosophila hairy gene demonstrate in vivo requirements for basic, helix-loop-helix, and WRPW domains. AB - The Drosophila pair-rule gene, hairy (h), encodes a nuclear basic helix-loop helix (bHLH) protein that regulates embryonic segmentation and adult bristle patterning. In both cases, the h protein behaves as a transcriptional repressor. In this study, we determined the molecular nature of 12 h alleles. One mutation maps within the HLH domain, consistent with h function requiring homodimerization or heterodimerization with other HLH proteins. A second mutation lies in the basic domain, suggesting that DNA binding is required for h activity. Several mutations show that the h C terminus, in particular the WRPW domain, is also required for h activity, perhaps by interacting with other proteins to mediate transcriptional repression. We show that the h protein in Drosophila virilis closely resembles that in D. melanogaster and includes completely conserved bHLH and WRPW domains. PMID- 1588952 TI - Expression of MRF4, a myogenic helix-loop-helix protein, produces multiple changes in the myogenic program of BC3H-1 cells. AB - Expression of MRF4, a myogenic regulatory factor of the basic helix-loop-helix type, produced multiple changes in the myogenic program of the BC3H-1 cell line. BC3H-1 cells that stably expressed exogenous MRF4 were prepared and termed BR cell lines. Upon differentiation, the BR cells were found to have three muscle specific properties (endogenous MyoD expression, myoblast fusion, and fast myosin light-chain 1 expression) that the parent BC3H-1 cells did not have. Of the four known myogenic regulatory factors (MyoD, myogenin, Myf-5, and MRF4), only MRF4 was capable of activating expression of the endogenous BC3H-1 myoD gene. In addition, the pattern of Myf-5 expression in BR cells was the opposite of that in BC3H-1 cells. Myf-5 expression was low in BR myoblasts and showed a small increase upon myotube formation, whereas Myf-5 expression was high in BC3H-1 myoblasts and decreased upon differentiation. Though the MRF4-transfected BR cells fused to form large myotubes and expressed fast myosin light-chain 1, the pattern of myosin heavy-chain isoform expression was the same in the BR and the nonfusing parent BC3H-1 cells, suggesting that factors in addition to the MyoD family members regulate myosin heavy-chain isoform expression patterns in BC3H-1 cells. In contrast to the changes produced by MRF4 expression, overexpression of Myf-5 did not alter BC3H-1 myogenesis. The results suggest that differential expression of the myogenic regulatory factors of the MyoD family may be one mechanism for generating cells with diverse myogenic phenotypes. PMID- 1588953 TI - Deregulated c-myb disrupts interleukin-6- or leukemia inhibitory factor-induced myeloid differentiation prior to c-myc: role in leukemogenesis. AB - The c-myb proto-oncogene is abundantly expressed in tissues of hematopoietic origin, and changes in endogenous c-myb genes have been implicated in both human and murine hematopoietic tumors. c-myb encodes a DNA-binding protein capable of trans-activating the c-myc promoter. Suppression of both of these proto-oncogenes was shown to occur upon induction of terminal differentiation but not upon induction of growth inhibition in myeloid leukemia cells. Myeloblastic leukemia M1 cells that can be induced for terminal differentiation with the physiological hematopoietic inducers interleukin-6 and leukemia inhibitory factor were genetically manipulated to constitutively express a c-myb transgene. By using immediate-early to late genetic and morphological markers, it was shown that continuous expression of c-myb disrupts the genetic program of myeloid differentiation at a very early stage, which precedes the block previously shown to be exerted by deregulated c-myc, thereby indicating that the c-myb block is not mediated via deregulation of c-myc. Enforced c-myb expression also prevents the loss in leukemogenicity of M1 cells normally induced by interleukin-6 or leukemia inhibitory factor. Any changes which have taken place, including induction of myeloid differentiation primary response genes, eventually are reversed. Also, it was shown that suppression of c-myb, essential for terminal differentiation, is not intrinsic to growth inhibition. Taken together, these findings show that c-myb plays a key regulatory role in myeloid differentiation and substantiate the notion that deregulated expression of c-myb can play an important role in leukemogenicity. PMID- 1588955 TI - Negative regulation of catalase gene expression in hepatoma cells. AB - For an understanding of the molecular basis of the marked decrease in catalase activity of various tumor cells, expression of the catalase gene was studied in rat and human hepatoma cell lines and in rat liver, which was used as a control with high activity. RNA blot hybridization profiles and run-on assays indicated that the decrease in catalase activity was due to depression of catalase gene transcription. Chloramphenicol acetyltransferase (CAT) assays for the fragments with various lengths of the 5'-flanking region (up to -4.5 kb from the ATG codon) of the catalase gene revealed the presence of several cis-acting elements involved in the negative regulation of transcription. The most-upstream element with the strongest activity (-3504 to -3364 bp), when linked to the catalase promoter region (-126 bp) of the CAT construct and subjected to an in vitro transcription assay, did not yield transcripts in experiments with the hepatoma nuclear extract, whereas the unlinked template did yield transcripts. A gel shift competition assay using hepatoma nuclear extract showed the core sequence of the silencer element to be 5'-TGGGGGGAG-3'. A homology search found that the same core sequence was also present in 5'-flanking regions of the albumin gene and of some other liver enzyme genes, the expression of which has been reported to be down regulated in some hepatoma cells. Southwestern (DNA-protein) analysis demonstrated that an approximately 35-kDa nuclear protein bound to the silencer element was present in hepatoma cells but not in rat liver cells. PMID- 1588954 TI - Nerve growth factor-induced derepression of peripherin gene expression is associated with alterations in proteins binding to a negative regulatory element. AB - The peripherin gene, which encodes a neuronal-specific intermediate filament protein, is transcriptionally induced with a late time course when nerve growth factor (NGF) stimulates PC12 cells to differentiate into neurons. We have studied its transcriptional regulation in order to better understand the neuronal specific end steps of the signal transduction pathway of NGF. By 5' deletion mapping of the peripherin promoter, we have localized two positive regulatory elements necessary for full induction by NGF: a distal positive element and a proximal constitutive element within 111 bp of the transcriptional start site. In addition, there is a negative regulatory element (NRE; -179 to -111), the deletion of which results in elevated basal expression of the gene. Methylation interference footprinting of the NRE defined a unique sequence, GGCAGGGCGCC, as the binding site for proteins present in nuclear extracts from both undifferentiated and differentiated PC12 cells. However, DNA mobility shift assays using an oligonucleotide probe containing the footprinted sequence demonstrate a prominent retarded complex in extracts from undifferentiated PC12 cells which migrates with slower mobility than do the complexes produced by using differentiated PC12 cell extract. Transfection experiments using peripherin chloramphenicol acetyltransferase constructs in which the footprinted sequence has been mutated confirm that the NRE has a functional, though not exclusive, role in repressing peripherin expression in undifferentiated and nonneuronal cells. We propose a two-step model of activation of peripherin by NGF in which dissociation of a repressor from the protein complex at the NRE, coupled with a positive signal from the distal positive element, results in depression of the gene. PMID- 1588956 TI - High-frequency germ line gene conversion in transgenic mice. AB - Gene conversion is the nonreciprocal transfer of genetic information between two related genes or DNA sequences. It can influence the evolution of gene families, having the capacity to generate both diversity and homogeneity. The potential evolutionary significance of this process is directly related to its frequency in the germ line. While measurement of meiotic inter- and intrachromosomal gene conversion frequency is routine in fungal systems, it has hitherto been impractical in mammals. We have designed a system for identifying and quantitating germ line gene conversion in mice by analyzing transgenic male gametes for a contrived recombination event. Spermatids which undergo the designed intrachromosomal gene conversion produce functional beta-galactosidase (encoded by the lacZ gene), which is visualized by histochemical staining. We observed a high incidence of lacZ-positive spermatids (approximately 2%), which were produced by a combination of meiotic and mitotic conversion events. These results demonstrate that gene conversion in mice is an active recombinational process leading to nonparental gametic haplotypes. This high frequency of intrachromosomal gene conversion seems incompatible with the evolutionary divergence of newly duplicated genes. Hence, a process may exist to uncouple gene pairs from frequent conversion-mediated homogenization. PMID- 1588957 TI - Growth-dependent inhibition of CCAAT enhancer-binding protein (C/EBP alpha) gene expression during hepatocyte proliferation in the regenerating liver and in culture. AB - As an approach to understanding physiological mechanisms that control the proliferation of highly differentiated cells, we are addressing whether certain hepatic transcription factors participate in mechanisms that control the growth of hepatocytes. We have focused on CCAAT enhancer-binding protein (C/EBP alpha), a transcription factor which is highly abundant in normal liver and is considered to regulate expression of many genes, including some involved in energy metabolism (S. L. McKnight, M. D. Lane, and S. Gluecksohn-Walsh. Genes Dev. 3:2021-2024, 1989). Using Northern (RNA) blot analysis, we have examined the expression of C/EBP alpha mRNA during liver regeneration and in primary cultures of hepatocytes. C/EBP alpha mRNA levels decrease 60 to 80% within 1 to 3 h after partial hepatectomy as the cells move from G0 to G1 and decrease further when cells progress into S phase. Run-on transcription analysis is in agreement with the Northern blot data, thus suggesting that C/EBP alpha is transcriptionally regulated in regenerating liver. C/EBP alpha mRNA expression also decreases dramatically during the growth of freshly isolated normal hepatocytes cultured under conventional conditions (on dried rat tail collagen; stimulated to proliferate by epidermal growth factor [EGF] and insulin). Cultures of hepatocytes on rat tail collagen in the presence or absence of EGF clearly show that within 3 h, EGF depresses C/EBP alpha mRNA expression and that this effect is substantially greater by 4 h. Inhibition of protein synthesis in the liver by cycloheximide or in cultured hepatocytes by puromycin or cycloheximide effectively blocks the down-regulation of C/EBP alpha gene expression, apparently by stabilizing the normal rapid turnover of the C/EBP alpha mRNA (half-life of <2 h). This drop in C/EBP alpha gene expression in response to activation of hepatocyte growth is consistent with the proposal that C/EBP alpha has an antiproliferative role to play in highly differentiated cells (R. M. Umek, A. D. Friedman, and S. L. McKnight, Science 251: 288-292, 1991). PMID- 1588958 TI - Saccharomyces cerevisiae contains an RNase MRP that cleaves at a conserved mitochondrial RNA sequence implicated in replication priming. AB - Yeast mitochondrial DNA contains multiple promoters that sponsor different levels of transcription. Several promoters are individually located immediately adjacent to presumed origins of replication and have been suggested to play a role in priming of DNA replication. Although yeast mitochondrial DNA replication origins have not been extensively characterized at the primary sequence level, a common feature of these putative origins is the occurrence of a short guanosine-rich region in the priming strand downstream of the transcriptional start site. This situation is reminiscent of vertebrate mitochondrial DNA origins and raises the possibility of common features of origin function. In the case of human and mouse cells, there exists an RNA processing activity with the capacity to cleave at a guanosine-rich mitochondrial RNA sequence at an origin; we therefore sought the existence of a yeast endoribonuclease that had such a specificity. Whole cell and mitochondrial extracts of Saccharomyces cerevisiae contain an RNase that cleaves yeast mitochondrial RNA in a site-specific manner similar to that of the human and mouse RNA processing activity RNase MRP. The exact location of cleavage within yeast mitochondrial RNA corresponds to a mapped site of transition from RNA to DNA synthesis. The yeast activity also cleaved mammalian mitochondrial RNA in a fashion similar to that of the mammalian RNase MRPs. The yeast endonuclease is a ribonucleoprotein, as judged by its sensitivity to nucleases and proteinase, and it was present in yeast strains lacking mitochondrial DNA, which demonstrated that all components required for in vitro cleavage are encoded by nuclear genes. We conclude that this RNase is the yeast RNase MRP. PMID- 1588959 TI - HAP1 and ROX1 form a regulatory pathway in the repression of HEM13 transcription in Saccharomyces cerevisiae. AB - HEM13 of Saccharomyces cerevisiae encodes coproporphyrinogen oxidase, an enzyme in the heme biosynthetic pathway. Expression of HEM13 is repressed by oxygen and heme. This study investigated the regulatory pathway responsible for the regulation of HEM13 expression. The transcriptional activator HAP1 is demonstrated to be required for the full-level expression of HEM13 in the absence of heme. It is also shown that the repression of HEM13 transcription caused by heme involves the HAP1 and ROX1 gene products; a mutation in either gene results in derepression of HEM13 expression. The heme-dependent expression of ROX1 was found to require functional HAP1, leading one to propose that repression of HEM13 results from a pathway involving HAP1-mediated regulation of ROX1 transcription in response to heme levels followed by ROX1-mediated repression of HEM13 transcription. In support of this model, expression of ROX1 under control of the GAL promoter was found to result in repression of HEM13 transcription in a hap1 mutant strain. The ability of ROX1 encoded by the galactose-inducible ROX1 construct to function in the absence of HAP1 indicates that the only role of HAP1 in repression of HEM13 is to activate ROX1 transcription. PMID- 1588960 TI - Posttranscriptional regulation of rat growth hormone gene expression: increased message stability and nuclear polyadenylation accompany thyroid hormone depletion. AB - In thyroid hormone-depleted rats, the rate of transcription of the growth hormone (GH) gene in the anterior pituitary gland is lower than the rate in euthyroid controls, and there is a corresponding reduction in the abundance of the GH mRNA. Concomitantly, the poly(A) tail of the GH mRNA increases in length. Examination of nuclear RNA from anterior pituitary glands of control and thyroid hormone depleted rats revealed no difference in the length of pre-mRNAs containing the first and last introns of the GH gene. However, mature nuclear GH RNA is differentially polyadenylated in euthyroid and hypothyroid animals. We suggest that the extent of polyadenylation of the GH transcript is regulated in the cell nucleus concomitant with or subsequent to the splicing of the pre-mRNA. Experiments with anterior pituitary gland explant cultures demonstrated that the GH mRNA from thyroid hormone-depleted rats is more stable than its euthyroid counterpart and that the poly(A) tail may contribute to the differential stability of free GH ribonucleoproteins. PMID- 1588962 TI - The promoter for the procyclic acidic repetitive protein (PARP) genes of Trypanosoma brucei shares features with RNA polymerase I promoters. AB - All eukaryotic protein-coding genes are believed to be transcribed by RNA polymerase (Pol) II. An exception may exist in the protozoan parasite Trypanosoma brucei, in which the genes encoding the variant surface glycoprotein (VSG) and procyclic acidic repetitive protein (PARP) are transcribed by an RNA polymerase that is resistant to the Pol II inhibitor alpha-amanitin. The PARP and VSG genes were proposed to be transcribed by Pol I (C. Shea, M. G.-S. Lee, and L. H. T. Van der Ploeg, Cell 50:603-612, 1987; G. Rudenko, M. G.-S. Lee, and L. H. T. Van der Ploeg, Nucleic Acids Res. 20:303-306, 1992), a suggestion that has been substantiated by the finding that trypanosomes can transcribe protein-coding genes by Pol I (G. Rudenko, H.-M. Chung, V. P. Pham, and L. H. T. Van der Ploeg, EMBO J. 10:3387-3397, 1991). We analyzed the sequence elements of the PARP promoter by linker scanning mutagenesis and compared the PARP promoter with Pol I, Pol II, and Pol III promoters. The PARP promoter appeared to be of limited complexity and contained at least two critical regions. The first was located adjacent to the transcription initiation site (nucleotides [nt] -69 to +12) and contained three discrete domains in which linker scanning mutants affected the transcriptional efficiency: at nt -69 to -56, -37 to -11, and -11 to +12. The second region was located between nt -140 and -131, and a third region may be located between nt -228 and -205. The nucleotide sequences of these elements, and their relative positioning with respect to the transcription initiation site did not resemble those of either Pol II or Pol III promoter elements, but rather reflected the organization of Pol I promoters in (i) similarity in the positioning of essential domains in the PARP promoter and Pol I promoter, (ii) strong sequence homology between the PARP core promoter element (nt -37 to -11) and identically positioned nucleotide sequences in the trypanosome rRNA and VSG gene promoters, and (iii) moderate effects on promoter activity of mutations around the transcription initiation site. PMID- 1588961 TI - STP1, a gene involved in pre-tRNA processing, encodes a nuclear protein containing zinc finger motifs. AB - STP1 is an unessential yeast gene involved in the removal of intervening sequences from some, but not all, families of intervening sequence-containing pre tRNAs. Previously, we proposed that STP1 might encode a product that generates pre-tRNA conformations efficiently recognized by tRNA-splicing endonuclease. To test the predictions of this model, we have undertaken a molecular analysis of the STP1 gene and its products. The STP1 locus is located on chromosome IV close to at least two other genes involved in RNA splicing: PRP3 and SPP41. The STP1 open reading frame (ORF) could encode a peptide of 64,827 Da; however, inspection of putative transcriptional and translational regulatory signals and mapping of the 5' ends of mRNA provide evidence that translation of the STP1 ORF usually initiates at a second AUG to generate a protein of 58,081 Da. The STP1 ORF contains three putative zinc fingers. The first of these closely resembles both the DNA transcription factor consensus and the Xenopus laevis p43 RNA-binding protein consensus. The third motif more closely resembles the fingers found in spliceosomal proteins. Employing antisera to the endogenous STP1 protein and to STP1-LacZ fusion proteins, we show that the STP1 protein is localized to nuclei. The presence of zinc finger motifs and the nuclear location of the STP1 protein support the model that this gene product is involved directly in pre-tRNA splicing. PMID- 1588963 TI - Anti-Cdc25 antibodies inhibit guanyl nucleotide-dependent adenylyl cyclase of Saccharomyces cerevisiae and cross-react with a 150-kilodalton mammalian protein. AB - The CDC25 gene product of the yeast Saccharomyces cerevisiae has been shown to be a positive regulator of the Ras protein. The high degree of homology between yeast RAS and the mammalian proto-oncogene ras suggests a possible resemblance between the mammalian regulator of Ras and the regulator of the yeast Ras (Cdc25). On the basis of this assumption, we have raised antibodies against the conserved C-terminal domain of the Cdc25 protein in order to identify its mammalian homologs. Anti-Cdc25 antibodies raised against a beta-galactosidase Cdc25 fusion protein were purified by immunoaffinity chromatography and were shown by immunoblotting to specifically recognize the Cdc25 portion of the antigen and a truncated Cdc25 protein, also expressed in bacteria. These antibodies were shown both by immunoblotting and by immunoprecipitation to recognize the CDC25 gene product in wild-type strains and in strains overexpressing Cdc25. The anti-Cdc25 antibodies potently inhibited the guanyl nucleotide-dependent and, approximately 3-fold less potently, the Mn(2+) dependent adenylyl cyclase activity in S. cerevisiae. The anti-Cdc25 antibodies do not inhibit cyclase activity in a strain harboring RAS2Val-19 and lacking the CDC25 gene product. These results support the view that Cdc25, Ras2, and Cdc35/Cyr1 proteins are associated in a complex. Using these antibodies, we were able to define the conditions to completely solubilize the Cdc25 protein. The results suggest that the Cdc25 protein is tightly associated with the membrane but is not an intrinsic membrane protein, since only EDTA at pH 12 can solubilize the protein. The anti-Cdc25 antibodies strongly cross-reacted with the C-terminal domain of the Cdc25 yeast homolog, Sdc25. Most interestingly, these antibodies also cross-reacted with mammalian proteins of approximately 150 kDa from various tissues of several species of animals. These interactions were specifically blocked by the beta-galactosidase-Cdc25 fusion protein. PMID- 1588964 TI - SRN1, a yeast gene involved in RNA processing, is identical to HEX2/REG1, a negative regulator in glucose repression. AB - The yeast RNA1 gene encodes a cytosolic protein that affects pre-tRNA splicing, pre-rRNA processing, the production of mRNA, and the export of RNA from the nucleus to the cytosol. In an attempt to understand how the RNA1 protein affects such a diverse set of processes, we sought second-site suppressors of a mutation, rna1-1, of the RNA1 locus. Mutations in a single complementation group were obtained. These lesions proved to be in the same gene, SRN1, identified previously in a search for second-site suppressors of mutations that affect the removal of intervening sequences from pre-mRNAs. The SRN1 gene was mapped, cloned, and sequenced. DNA sequence analysis and the phenotype of disruption mutations showed that, surprisingly, SRN1 is identical to HEX2/REG1, a gene that negatively regulates glucose-repressible genes. Interestingly, SRN1 is not a negative regulator of RNA1 at the transcriptional, translational, or protein stability level. However, SRN1 does regulate the level of two newly discovered antigens, p43 and p70, one of which is not glucose repressible. These studies for the first time link RNA processing and carbon catabolite repression. PMID- 1588965 TI - Characterization of the DNA-binding activity of GCR1: in vivo evidence for two GCR1-binding sites in the upstream activating sequence of TPI of Saccharomyces cerevisiae. AB - GCR1 gene function is required for high-level glycolytic gene expression in Saccharomyces cerevisiae. Recently, we suggested that the CTTCC sequence motif found in front of many genes encoding glycolytic enzymes lay at the core of the GCR1-binding site. Here we mapped the DNA-binding domain of GCR1 to the carboxy terminal 154 amino acids of the polypeptide. DNase I protection studies showed that a hybrid MBP-GCR1 fusion protein protected a region of the upstream activating sequence of TPI (UASTPI), which harbored the CTTCC sequence motif, and suggested that the fusion protein might also interact with a region of the UAS that contained the related sequence CATCC. A series of in vivo G methylation protection experiments of the native TPI promoter were carried out with wild-type and gcr1 deletion mutant strains. The G doublets that correspond to the C doublets in each site were protected in the wild-type strain but not in the gcr1 mutant strain. These data demonstrate that the UAS of TPI contains two GCR1 binding sites which are occupied in vivo. Furthermore, adjacent RAP1/GRF1/TUF- and REB1/GRF2/QBP/Y-binding sites in UASTPI were occupied in the backgrounds of both strains. In addition, DNA band-shift assays were used to show that the MBP GCR1 fusion protein was able to form nucleoprotein complexes with oligonucleotides that contained CTTCC sequence elements found in front of other glycolytic genes, namely, PGK, ENO1, PYK, and ADH1, all of which are dependent on GCR1 gene function for full expression. However, we were unable to detect specific interactions with CTTCC sequence elements found in front of the translational component genes TEF1, TEF2, and CRY1. Taken together, these experiments have allowed us to propose a consensus GCR1-binding site which is 5' (T/A)N(T/C)N(G/A)NC(T/A)TCC(T/A)N(T/A)(T/A)(T/G)-3'. PMID- 1588966 TI - Instability of simple sequence DNA in Saccharomyces cerevisiae. AB - All eukaryotic genomes thus far examined contain simple sequence repeats. A particularly common simple sequence in many organisms (including humans) consists of tracts of alternating GT residues on one strand. Allelic poly(GT) tracts are often of different lengths in different individuals, indicating that they are likely to be unstable. We examined the instability of poly(GT) and poly(G) tracts in the yeast Saccharomyces cerevisiae. We found that these tracts were dramatically unstable, altering length at a minimal rate of 10(-4) events per division. Most of the changes involved one or two repeat unit additions or deletions, although one alteration involved an interaction with the yeast telomeres. PMID- 1588967 TI - Functional dissection of the lck proximal promoter. AB - The lck gene encodes a protein tyrosine kinase that participates in lymphocyte specific signal transduction pathways. Previous studies have established that lck transcription is regulated by two distinct promoter elements termed proximal (or 3') and distal (or 5'). The proximal promoter is active almost exclusively in thymocytes and becomes inactive later during T-cell maturation. To dissect the mechanisms responsible for lck gene regulation, we generated transgenic animals bearing 5' truncations in the proximal promoter element. Sequences between -584 and +37 with respect to the proximal promoter transcription start site act to direct tissue-specific and temporally correct transcription of either a tagged version of the lck gene itself or a heterologous reporter sequence (lacZ). This region contains binding sites for at least five distinct nuclear proteins, of which one is found only in cells that support proximal lck promoter activity and a second appears only in nonexpressing cells. Interestingly, the transcribed region of the lck gene contains positive control elements that can substantially boost expression from minimal (-130 bp) proximal promoter constructs. These results provide a basis for the biochemical dissection of transcriptional regulators that act at defined points during T-cell development. PMID- 1588968 TI - Investigation of coelectroporation as a method for introducing small mutations into embryonic stem cells. AB - We have investigated coelectroporation as a method for introducing minor genetic changes into specific genes in embryonic stem cells. A selectable marker (neo) and a targeting replacement vector designed to insert a 4-bp insertion into exon 3 of the mouse hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene were coelectroporated into embryonic stem cells and selected in G418 and 6-thioguanine (6-TG). HPRT-negative clones were obtained at a frequency of approximately 1 per 520 G418r clones. Southern analysis and the polymerase chain reaction were used to demonstrate that 3 of 36 of the 6-TG-resistant clones had the desired 4-bp insertion without any other disruption of the HPRT locus. Initial studies indicated that the other 33 6-TG-resistant clones probably resulted from the targeted integration of a concatemer containing both the targeting construct and the selectable neo gene. PMID- 1588969 TI - Isolation of telomerelike sequences from Cryptococcus neoformans and their use in high-efficiency transformation. AB - Development of a transformation system for the fungal human pathogen Cryptococcus neoformans is an important prerequisite for the identification of genes involved in virulence. It has previously been reported that low-efficiency transformation can be achieved by using the cloned C. neoformans URA5 gene and ura5 mutants. The introduction of linearized URA5 vectors into C. neoformans resulted in unstable transformants which apparently harbored linear extrachromosomal DNA molecules. In this paper, the nature of these molecules is confirmed to be linear by exonuclease digestion. Recovery of the extrachromosomal DNA in Escherichia coli and sequence analysis demonstrates that repeats characteristic of telomeric DNA have been added to the ends of the introduced DNA. The recovered plasmids are capable of transforming at much higher efficiencies either in the supercoiled state (up to 200 transformants per microgram) or the linear state (up to 90,000 transformants per microgram). PMID- 1588970 TI - Mutations in the zinc fingers of ADR1 that change the specificity of DNA binding and transactivation. AB - ADR1 is a yeast transcription factor that contains two zinc fingers of the Cys-2 His-2 (C2H2) class. Mutations that change the specificity of DNA binding of ADR1 to its target site, upstream activation sequence 1 (UAS1), have been identified at three positions in the first zinc finger. Mutations Arg-115 to Gln, His-118 to Thr, and Arg-121 to Asn led to new specificities of DNA binding at adjacent positions 10, 9, and 8 (3'-GAG-5') in UAS1. Arg-115 is at the finger tip, and His 118 and Arg-121 are at positions 3 and 6, respectively, in the alpha helix of finger 1. One double mutant displayed the binding specificity expected from the properties of its constituent new-specificity mutations. Mutations in the second finger that allowed its binding site to be identified through loss-of-contact phenotypes were made. These mutations imply a tail-to-tail orientation of the two ADR1 monomers on their adjacent binding sites. Finger 1 is aligned on UAS1 in an amino-to-carboxyl-terminal orientation along the guanine-rich strand in a 3'-to 5' direction. One of the ADR1 mutants was functional in vivo with both its cognate binding site and wild-type UAS1, but the other two mutants were defective in transactivation despite their ability to bind with high affinity to their cognate binding sites. PMID- 1588971 TI - Identification of a novel enhancer element mediating calcium-dependent induction of gene expression in response to either epidermal growth factor or activation of protein kinase C. AB - The VL30 family of defective murine retroviruses consists of 100 to 200 members, of which fewer than 5% appear to be transcriptionally active. A genomic clone of the transcriptionally active VL30 element RVL-3 was identified and sequenced. Genetic analysis indicated that a triple-repeat sequence within the RVL-3 long terminal repeat is capable of functioning as an inducible enhancer element responding to a variety of agonists. In Rat-1 fibroblasts, the ability of the RVL 3 enhancer to mediate induction of gene expression from a heterologous promoter in response to either epidermal growth factor (EGF) or phorbol ester treatment required coelevation of intracellular calcium. Two CArG boxes present in the triple-repeat sequence appeared to exert a negative effect on gene expression, as mutation of these sequences elevated the basal level of expression observed without altering the fold induction in response to either EGF or protein kinase C activation. In the presence of these CArG elements, mutation of AP-1-like sites adjacent to the CArG elements significantly inhibited the ability of either EGF or phorbol esters to induce gene expression. The effect of mutating these AP-1 like sites was relieved by simultaneous mutation of the CArG sites, indicating that interactions among these sites modulate RVL-3 expression. Mutational analysis and gel mobility shift experiments have identified a third sequence within the VL30 triple-repeat element that is required for the induction of gene expression and serves as a binding site for nuclear proteins. Sequence comparisons indicate that this enhancer element has not been described previously. PMID- 1588972 TI - Activation of a mammalian origin of replication by chromosomal rearrangement. AB - The methotrexate-resistant Chinese hamster cell line DC3F/A3-4K (A3/4K) contains at least two prominent dihydrofolate reductase amplicon types. The type I amplicons, constituting approximately 80% of the total, are at least 650 kb in length, but the endpoints have not yet been characterized. The type II sequences represent approximately 20% of amplicons, are 450 kb in length, and are arranged as alternating head-to-head and tail-to-tail repeats. In previous studies on the CHOC 400 line, in which the amplicons are much smaller, a replication initiation locus (ori-beta/ori-gamma) has been shown to reside downstream from the dihydrofolate reductase gene. In a more recent study on the larger amplicons of A3/4K cells, we detected an additional initiation locus (ori-alpha) lying approximately 240 kb upstream from ori-beta/ori-gamma. Interestingly, in vivo labelling experiments suggested that replication forks diverge from ori-alpha only in the downstream direction. This finding suggested either that ori-alpha is a unidirectional origin or that a terminus lies immediately upstream from ori alpha. However, in this study, we show that ori-alpha is actually very close to the head-to-head palindromic junction sequence between the minor type II amplicons in A3/4K cells; furthermore, ori-alpha is active in the early S period in the type II amplicons but not in the larger type I sequences that lack this palindromic junction. This is the first direct demonstration in mammalian cells that a cryptic origin can be activated by chromosomal rearrangement, presumably by deleting negative regulatory elements or by creating a more favorable chromosomal milieu for initiation. PMID- 1588973 TI - Role of the liver-enriched transcription factor DBP in expression of the cytochrome P450 CYP2C6 gene. AB - The CYP2C6 gene becomes maximally transcriptionally activated in livers of postpubertal rats. We examined the role of upstream DNA and liver-specific transcription factors in regulation of this promoter by use of transient transfection of heterologous chloramphenicol acetyltransferase gene constructs and vectors containing cDNAs encoding the liver-enriched transcription factors HNF-1 alpha, C/EBP, and DBP. Only DBP was able to activate the CYP2C6 promoter in HepG2 cells. Transactivation was not observed in one mouse and two human nonhepatic origin cell lines tested. Analysis of various constructs in which CYP2C6 upstream DNA was deleted revealed that DNA between -38 to -103 was involved in DBP-mediated activation. A partially purified preparation of DBP produced a footprint between -43 and -64 bp upstream of the transcription start site. A 32P-labeled double-stranded oligonucleotide, containing sequence information corresponding to -40 to -65, bound to both partially pure DBP and extracts from livers of rats as young as 1 week and as old as 25 weeks of age, as assessed by gel mobility shift analysis. This binding was eliminated by coincubation with excess unlabeled -40/-65 double-stranded oligonucleotide and by an oligonucleotide corresponding to the D site of the rat albumin gene. A gel mobility shift-Western immunoblot analysis revealed that the -40/-65 sequence bound to DBP only in liver nuclear extracts from rats older than 3 weeks; maximal binding was observed by 7 weeks of age, and no binding was detected from 1-week old rat liver extracts. Interestingly, the DBP-binding regions of both CYP2C6 and albumin bind to C/EBP, but this factor is capable of transactivating only the latter gene. Although the DBP-binding regions in these two genes share no obvious sequence similarities, the CYP2C6 region contains consensus palindromic half sites for DBP-related binding proteins and affinity for recombinant DBP of 17 fold greater than that of the D site of albumin. This difference in affinity is probably responsible for the markedly lower amounts of DBP required for half maximal activation of the CYP2C6 promoter, as compared with the albumin promoter, in transactivation transfection assays. These data indicate that the CYP2C6 gene may be regulated, at least in part, by DBP, a liver transcription factor produced when rats reach puberty that may also be involved in maintenance of albumin gene transcription. PMID- 1588974 TI - A transcriptionally active DNA-binding site for human p53 protein complexes. AB - Recent studies have demonstrated transcriptional activation domains within the tumor suppressor protein p53, while others have described specific DNA-binding sites for p53, implying that the protein may act as a transcriptional regulatory factor. We have used a reiterative selection procedure (CASTing: cyclic amplification and selection of targets) to identify new specific binding sites for p53, using nuclear extracts from normal human fibroblasts as the source of p53 protein. The preferred consensus is the palindrome GGACATGCCCGGGCATGTCC. In vitro-translated p53 binds to this sequence only when mixed with nuclear extracts, suggesting that p53 may bind DNA after posttranslational modification or as a complex with other protein partners. When placed upstream of a reporter construct, this sequence promotes p53-dependent transcription in transient transfection assays. PMID- 1588975 TI - Anatomy of an unusual RNA polymerase II promoter containing a downstream TATA element. AB - The adenovirus type 2 IVa2 promoter lacks a conventional TATA element yet directs transcription from two closely spaced initiation sites. To define elements required for in vitro transcription of this promoter, IVa2 templates carrying 5' deletions or linker-scanning mutations were transcribed in HeLa whole-cell extracts and the transcripts were analyzed by primer extension. Mutation of the sequence centered on position -47, which is specifically recognized by a cellular factor, reduced the efficiency of IVa2 transcription two- to threefold, whereas mutation of the sequence centered on position -30 selectively impaired utilization of the minor in vivo initiation site. Utilization of the major in vivo site was decreased no more than fivefold by deletion of all sequences upstream of position -15. By contrast, mutation of the region from +13 to +19 or of the initiation region severely impaired IVa2 transcription. The sequence spanning the initiation sites was sufficient to direct accurate initiation by RNA polymerase II from the major in vivo site. Thus, the two initiation sites of the IVa2 promoter are specified by independent elements, and a downstream element is the primary determinant of efficient transcription from both of these sites. The downstream element identified by mutational analysis altered the TATA element like sequence TATAGAAA lying at positions +21 to +14 in the coding strand. Transcription from the wild-type IVa2 promoter was severely inhibited when endogenous TFIID was inactivated by mild heat treatment. Exogenous human TATA binding protein (TBP) synthesized in Escherichia coli restored specific IVa2 transcription from both initiation sites when added to such heat-treated extracts. Although efficient IVa2 transcription requires both the downstream TATA sequence and active TFIID, bacterially synthesized TBP also stimulated the low level of IVa2 transcription observed when the TATA sequence was mutated to a sequence that failed to bind TBP. PMID- 1588976 TI - Rapid induction in regenerating liver of RL/IF-1 (an I kappa B that inhibits NF kappa B, RelB-p50, and c-Rel-p50) and PHF, a novel kappa B site-binding complex. AB - The liver is one of the few adult tissues that has the capacity to regenerate following hepatectomy or toxic damage. In examining the early growth response during hepatic regeneration, we found that a highly induced immediate-early gene in regenerating liver encodes RL/IF-1 (regenerating liver inhibitory factor) and is the rat homolog of human MAD-3 and probably of chicken pp40. RL/IF-1 has I kappa B activity of broad specificity in that it inhibits the binding of p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50, but not p50 homodimeric NF-kappa B, to kappa B sites. Like RL/IF-1, several members of the NF-kappa B and rel family of transcription factors are immediate-early genes in regenerating liver and mitogen treated cells. We examined changes in kappa B site binding activity during liver regeneration and discovered a rapidly induced novel kappa B site-binding complex designated PHF [posthepatectomy factor(s)]. PHF is induced over 1,000-fold within minutes posthepatectomy in a protein synthesis-independent manner, with peak activity at 30 min, and is not induced by sham operation. PHF is distinct from p50-p65 NF-kappa B, which is present only in the inactive form in liver posthepatectomy. Although early PHF complexes do not interact strongly with anti p50 antibodies, PHF complexes present later (3 to 5 h) posthepatectomy react strongly, suggesting that they contain a p50 NF-kappa B subunit. Unlike p50-p65 NF-kappa B, c-Rel-p50, and RelB-p50 complexes, PHF binding to kappa B sites is not inhibited by RL/IF-1. One role of RL/IF-1 in liver regeneration may be to inhibit p50-p65 NF-kappa B activity present in hepatic cells, allowing for the preferential binding of PHF to kappa B sites. Because PHF is induced immediately posthepatectomy in the absence of de novo protein synthesis, PHF could have a role in the regulation of liver-specific immediate-early genes in regenerating liver. PMID- 1588977 TI - Breast augmentation: a risk factor for breast cancer? AB - BACKGROUND: A relation between breast augmentation and the subsequent risk of breast cancer has been postulated. Since an estimated 2 million women in the United States alone have received breast implants, even a small increase in the risk of breast cancer could have considerable public health consequences. METHODS: We performed a population-based nonconcurrent cohort-linkage study. All women in Alberta, Canada, who underwent cosmetic breast augmentation from 1973 through 1986 were included in the implant cohort (n = 11,676). This cohort was compared with the cohort of all women in Alberta in whom a first primary breast cancer was diagnosed (n = 13,557). The expected number of breast-cancer cases in the implant cohort was estimated by applying age-specific and calendar year- specific incidence rates of breast cancer (obtained from the Alberta Cancer Registry) to the implant cohort. Standardized incidence ratios were calculated by dividing the observed by the expected number of breast-cancer cases in the implant cohort. RESULTS: Forty-one patients with implants were subsequently found to have breast cancer. The expected number was 86.2. The standardized incidence ratio was thus 47.6 percent, significantly lower than expected (P less than 0.01). The average length of follow-up in the implant cohort was 10.2 years, and the average length of time from breast augmentation to the diagnosis of breast cancer was 7.5 years. CONCLUSIONS: Women who undergo breast augmentation with silicone implants have a lower risk of breast cancer than the general population. This finding suggests that these women are drawn from a population already at low risk and that the implants do not substantially increase the risk. PMID- 1588978 TI - Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. International Kidney Biopsy Registry of Cyclosporine in Autoimmune Diseases. AB - BACKGROUND: Cyclosporine is an immunosuppressive drug that is used to treat patients with autoimmune disease as well as patients who have received allografts. The drug can cause renal damage, but the incidence of and risk factors for nephropathy in patients treated with cyclosporine for autoimmune or inflammatory diseases are not known. METHODS: We analyzed data from renal biopsies performed in 192 patients (129 adults and 63 children) who had been treated with cyclosporine for insulin-dependent diabetes mellitus of recent onset, uveitis, psoriasis, Sjogren's syndrome, or polychondritis. The mean (+/- SD) initial dose of cyclosporine was 8.2 +/- 2.8 mg per kilogram of body weight per day, and the duration of treatment was 4 to 39 months (median, 13). RESULTS: Forty-one patients (37 adults and 4 children) had cyclosporine-induced nephropathy, defined as at least moderate focal interstitial fibrosis with tubular atrophy, arteriolar alterations, or both. As compared with patients in whom nephropathy did not develop, these patients received a larger initial dose of cyclosporine (9.3 +/- 2.8 vs. 8.0 +/- 2.8 mg per kilogram per day), had a larger maximal increase in the serum creatinine concentration above base-line values (101 +/- 77 percent vs. 50 +/- 33 percent), and were older (31 +/- 13 vs. 23 +/- 12 years). These three variables were shown by multivariate logistic regression analysis to be significant risk factors. The duration of the elevation in the serum creatinine concentration and the occurrence of elevated blood pressure were not additional risk factors. CONCLUSIONS: Nephropathy is an important potential effect of cyclosporine therapy. The risk of its development in patients with autoimmune diseases who are treated with cyclosporine can be minimized by allowing a dose no higher than 5 mg per kilogram per day and avoiding increases in serum creatinine of more than 30 percent above the patient's base-line value. PMID- 1588980 TI - Usefulness of MRI in aortic dissection. PMID- 1588979 TI - Improvement in exercise performance by inhalation of methoxamine in patients with impaired left ventricular function. AB - BACKGROUND: Bronchial hyperresponsiveness to cholinergic stimuli such as the inhalation of methacholine is common in patients with impaired left ventricular function. Such hyperresponsiveness is best explained by cholinergic vasodilation of blood vessels in the small airways, with extravasation of plasma due to high left ventricular filling pressure. Because this vasodilation may be prevented by the inhalation of the vasoconstrictor agent methoxamine, we studied the effect of methoxamine on exercise performance in patients with chronic left ventricular dysfunction. METHODS: We studied 19 patients with a mean left ventricular ejection fraction of 22 +/- 4 percent and moderate exertional dyspnea. In the first part of the study, we performed treadmill exercise tests in 10 patients (group 1) at a constant maximal workload to assess the effects of 10 mg of inhaled methoxamine on the duration of exercise (a measure of endurance). In the second part of the study, we used a graded exercise protocol in nine additional patients (group 2) to assess the effects of inhaled methoxamine on maximal exercise capacity and oxygen consumption. Both studies were carried out after the patients inhaled methoxamine or placebo given according to a randomized, double blind, crossover design. RESULTS: In group 1, the mean (+/- SD) duration of exercise increased from 293 +/- 136 seconds after the inhalation of placebo to 612 +/- 257 seconds after the inhalation of methoxamine (P = 0.001). In group 2, exercise time (a measure of maximal exercise capacity) increased from 526 +/- 236 seconds after placebo administration to 578 +/- 255 seconds after methoxamine (P = 0.006), and peak oxygen consumption increased from 18.5 +/- 6.0 to 20.0 +/- 6.0 ml per minute per kilogram of body weight (P = 0.03). CONCLUSIONS: The inhalation of methoxamine enhanced exercise performance in patients with chronic left ventricular dysfunction. However, the improvement in the duration of exercise at a constant workload (endurance) was much more than the improvement in maximal exercise capacity assessed with a progressive workload. These data suggest that exercise-induced vasodilation of airway vessels may contribute to exertional dyspnea in such patients. Whether or not inhaled methoxamine can provide long term benefit in patients with heart failure will require further study. PMID- 1588981 TI - Advances in neurology (2). PMID- 1588982 TI - Initial management of ingestions of toxic substances. PMID- 1588983 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 25--1992. A 33-year-old woman with cirrhosis and right ventricular failure. PMID- 1588984 TI - Cyclosporine therapy for autoimmune disease. PMID- 1588985 TI - Breast implants--protection or paternalism? PMID- 1588986 TI - The silicone controversy--when will science prevail? PMID- 1588987 TI - Sporadic cases of Legionnaires' disease. PMID- 1588988 TI - Sporadic cases of Legionnaires' disease. PMID- 1588989 TI - Sporadic cases of Legionnaires' disease. PMID- 1588990 TI - Sporadic cases of Legionnaires' disease. PMID- 1588991 TI - Detection of HIV in specimens from newborn screening programs. PMID- 1588992 TI - Synthetic surfactants in infants with respiratory distress syndrome. PMID- 1588993 TI - Synthetic surfactants in infants with respiratory distress syndrome. PMID- 1588994 TI - Dietary iron overload. PMID- 1588995 TI - Dietary iron overload. PMID- 1588996 TI - Recent advances in dermatology. PMID- 1588997 TI - Recent advances in dermatology. PMID- 1588999 TI - Growing with environmental care. PMID- 1588998 TI - The American health care system. Private insurance. PMID- 1589000 TI - Anti-environment Bush. PMID- 1589001 TI - DNA feud. PMID- 1589003 TI - The great fungus. PMID- 1589004 TI - NIH scientists chafe under ethics rules on industry ties. PMID- 1589002 TI - Realities behind riots. PMID- 1589005 TI - Swiss vote for biotechnology, with controls. PMID- 1589006 TI - Germany to shift funding from physics to biology. PMID- 1589007 TI - India goes to sea for research funds. PMID- 1589008 TI - Botswana needs science help to save plant and animal species. PMID- 1589009 TI - Nobel Laureate David Baltimore would be leaving the Rockefeller University. PMID- 1589010 TI - Choosing the limits to life. PMID- 1589011 TI - Of animals and men. PMID- 1589012 TI - Of animals and men. PMID- 1589013 TI - Of animals and men. PMID- 1589014 TI - Rage and confusion hide role of HIV. PMID- 1589015 TI - Fungal physiology. Yeast branches out. PMID- 1589016 TI - Vampire wedding. PMID- 1589017 TI - Antigen presentation. Flying the first class flag. PMID- 1589018 TI - Enzyme complexes. A farewell to arms. PMID- 1589019 TI - Original and artificial antibodies. PMID- 1589020 TI - The crystal structure of diphtheria toxin. AB - The crystal structure of the diphtheria toxin dimer at 2.5 A resolution reveals a Y-shaped molecule of three domains. The catalytic domain, called fragment A, is of the alpha + beta type. Fragment B actually consists of two domains. The transmembrane domain consists of nine alpha-helices, two pairs of which are unusually apolar and may participate in pH-triggered membrane insertion and translocation. The receptor-binding domain is a flattened beta-barrel with a jelly-roll-like topology. Three distinct functions of the toxin, each carried out by a separate structural domain, can be useful in designing chimaeric proteins, such as immunotoxins, in which the receptor-binding domain is substituted with antibodies to target other cell types. PMID- 1589021 TI - Female swallow preference for symmetrical male sexual ornaments. AB - Many secondary sexual characters are supposed to have evolved as a response to female choice of the most extravagantly ornamented males, a hypothesis supported by studies demonstrating female preferences for the most ornamented males. Comparative studies of elaborate feather ornaments in birds have shown that (1) ornaments have larger degrees of fluctuating asymmetry (small, random deviations from bilateral symmetry caused by an inability of individuals to cope with environmental and genetic stress during development of a character) than other morphological traits, and (2) the degree of fluctuating asymmetry is often negatively related to the size of the ornament. The negative relationship between ornament asymmetry and size suggests that ornament size reliably reflects male quality because the largest secondary sex traits demonstrate the least degree of fluctuating asymmetry. I manipulated tail length and tail asymmetry independently in male swallows (Hirundo rustica) to determine whether ornament size or asymmetry were used as cues in mate choice. Male swallows with elongated, symmetric tails mated earlier, and enjoyed larger annual reproductive success than did males with shortened tails and increased asymmetry. Females therefore prefer large as well as symmetric ornaments, which suggests that females in their mate choice use ornament asymmetry and size as reliable indicators of male quality. PMID- 1589022 TI - Involvement of p21ras in Xenopus mesoderm induction. AB - During early vertebrate embryogenesis, mesoderm is specified by a signal emanating from prospective endoderm. This signal can respecify Xenopus prospective ectoderm as mesoderm, and can be mimicked by members of the fibroblast growth factor and transforming growth factor-beta families. In other systems, the p21c-ras proto-oncogene product has been implicated in signal transduction for various polypeptide growth factors. We report here that a dominant inhibitory ras mutant blocks the mesoderm-inducing activity of fibroblast growth factor and activin, as well as the endogenous inducing activity of prospective endoderm. A constitutively active ras mutant partially mimics these activities. These results indicate that p21ras may have a central role in the transduction of the mesoderm inductive signal. Basic fibroblast growth factor and activin have emerged as candidates for endogenous mesoderm-inducing molecules. The character of the mesoderm induced by these two factors is overlapping but distinct when assessed both by histological and molecular criteria. The signal transduction pathways used during induction by these factors are unknown. We used messenger RNA microinjection of Xenopus eggs to express a dominant inhibitory mutant ras, p21(Asn 17)Ha-ras, in cells competent to respond to inducing factors to examine the role of p21ras in this response. This mutant, which has a reduced affinity for GTP relative to GDP, blocks a variety of mitogenic signals in 3T3 fibroblasts as well as the differentiation of pheochromocytoma cells in response to nerve growth factor. PMID- 1589023 TI - Induction of gut in Caenorhabditis elegans embryos. AB - Two types of developmental events can cause an embryonic cell to adopt a fate different from that of its neighbours: during a cell division particular contents may be segregated to only one daughter cell and cells may experience different external cues, commonly in the form of inductive cell interactions. Work on development in the nematode Caenorhabditis elegans suggests that most cell fates are specified without a need for cell interactions. In particular, the gut cell lineage of C. elegans has been used as a primary example of specification by differential segregation of determinants. Here I re-examine the role of induction in gut specification by isolating early blastomeres. In C. elegans, the gut derives from all the progeny of a single blastomere (E) of the eight-cell stage. When a gut precursor cell (EMS) is isolated during the first half of the four cell stage, gut does not differentiate. Gut differentiation is rescued by recombining EMS with its posterior neighbour (P2), but not by recombining EMS with one or both of the other two cells of the four-cell stage. These results demonstrate that P2 induces EMS to form gut in C. elegans. PMID- 1589024 TI - The rate of actin-based motility of intracellular Listeria monocytogenes equals the rate of actin polymerization. AB - The Gram-positive bacterium Listeria monocytogenes is a facultative intracellular pathogen capable of rapid movement through the host cell cytoplasm. The biophysical basis of the motility of L. monocytogenes is an interesting question in its own right, the answer to which may shed light on the general processes of actin-based motility in cells. Moving intracellular bacteria display phase-dense 'comet tails' made of actin filaments, the formation of which is required for bacterial motility. We have investigated the dynamics of the actin filaments in the comet tails using the technique of photoactivation of fluorescence, which allows monitoring of the movement and turnover of labelled actin filaments after activation by illumination with ultraviolet light. We find that the actin filaments remain stationary in the cytoplasm as the bacterium moves forward, and that length of the comet tails is linearly proportional to the rate of movement. Our results imply that the motile mechanism involves continuous polymerization and release of actin filaments at the bacterial surface and that the rate of filament generation is related to the rate of movement. We suggest that actin polymerization provides the driving force for bacterial propulsion. PMID- 1589025 TI - DNA fingerprinting transforms the art of cell authentication. AB - The increasing diversity of new cell cultures is seriously stretching the capabilities of traditional methods of identification. DNA fingerprinting is set to play an important role in increasing confidence in the authenticity of cultures in research and industry. PMID- 1589026 TI - Congress compromises on rules governing NIH policies. PMID- 1589027 TI - Max Planck supports research in east as cost of reunification climbs. PMID- 1589028 TI - NIH defends gene patents as filing deadline approaches. PMID- 1589029 TI - Canada's medical council wants larger role. PMID- 1589030 TI - Congress slashes "silly titles". PMID- 1589031 TI - Running in the family. PMID- 1589032 TI - Endangered species and the law. AB - Taxonomy does not deserve its reputation as an arcane science. As the following examples from ungulate taxonomy show, classification has important implications for conservation legislation. PMID- 1589033 TI - DNA--protein interactions. HMG has DNA wrapped up. PMID- 1589034 TI - Earliest known simian primate found in Algeria. AB - The record of early fossil Simiiformes (Anthropoidea) from the Late Eocene and Early Oligocene of Africa and the Arabian Peninsula has increased dramatically in recent years. We report here the discovery of a new, diminutive and much older (Early or Middle Eocene) simian from an Algerian locality, Glib Zegdou. This species is smaller than any other living or fossil African simiiform. Derived similarities shared with Aegyptopithecus suggest that the new genus is more closely related to propliopithecines than to oligopithecines, implying that these two subfamilies differentiated during the Early Eocene. The new discovery confirms predictions about the great antiquity of Simiiformes and emphasizes a long and endemic African history for higher primates. PMID- 1589035 TI - New recombinant HLA-B alleles in a tribe of South American Amerindians indicate rapid evolution of MHC class I loci. AB - Evidence suggests that the New World was colonized only 11,000-40,000 years ago by Palaeo-Indians. The descendants of these Palaeo-Indians therefore provide a unique opportunity to study the effects of selection on major histocompatibility complex class I genes over a short period. Here we analyse the class I alleles of the Waorani of South America and the Zuni of North America. Four of the Waorani HLA-B alleles were new functional variants which could be accounted for by intralocus recombination. In contrast, all of the Zuni HLA-A and -B molecules were present in caucasians and orientals. This suggests that the new Waorani HLA B variants arose in South America. The description of four new HLA-B alleles in the Waorani and another five new HLA-B alleles from two other tribes of South American Amerindians indicates that the HLA-B locus can evolve rapidly in isolated populations. These studies underline the importance of gathering genetic data on endangered native human populations. PMID- 1589036 TI - Location of MHC-encoded transporters in the endoplasmic reticulum and cis-Golgi. AB - Immune recognition of intracellular proteins is mediated by major histocompatibility complex (MHC) class I molecules that present short peptides to cytotoxic T cells. Evidence suggests that peptides arise by cleavage of proteins in the cytoplasm and are transported by a signal-independent mechanism into a pre Golgi region of the cell, where they take part in the assembly of class I heavy chains with beta 2-microglobulin (reviewed in refs 5-7). Analysis of cells that have defects in class I molecule assembly and antigen presentation has shown that this phenotype can result from mutations in either of the two ABC transporter genes located in the class II region of the MHC. This suggested that the protein complex encoded by these two genes transports peptides from the cytosol into the endoplasmic reticulum. Here we report additional evidence by showing that the transporter complex is located in the endoplasmic reticulum membrane and is probably oriented with its ATP-binding domains in the cytosol. PMID- 1589038 TI - Nursing is not recession-proof. PMID- 1589037 TI - [Biosynthesis of peptides: a non-ribosomal system]. AB - The biosynthesis of peptides in nonribosomal systems is accomplished by complex multienzymes. These multienzymes assemble the required template for the construction of each natural product in the form of linearly coupled modules. This organization principle permits the integration of multistep synthetic processes on a single macromolecule. PMID- 1589039 TI - Nursing's new responsibility. PMID- 1589040 TI - Essentials for nurses in the year 2000. AB - As the health care delivery system changes ever faster, nursing is positioned to play a larger role than ever before. Such a role demands cognitive skills that nursing has yet to embrace effectively. A selected group of these essential skills is offered for consideration. PMID- 1589041 TI - Are health care costs really the costs of caring for health? PMID- 1589042 TI - Critical care in a baccalaureate program. AB - The combination of increased patient acuity levels and the nursing shortage has increased the demand for critical care nurses. This situation suggested a need for collaboration between nursing education and practice in order to prepare new graduate nurses to enter practice in critical care areas. Faculty from a baccalaureate program and educators and administrators from acute care agencies formed an advisory committee to develop a critical care elective to be offered concurrently with the last clinical preceptorship experience in the baccalaureate sequence. Evaluations of the course revealed that students felt that the course increased their knowledge base and affected their decision to seek employment in critical care as a graduate nurse. The agencies found that the course facilitated recruitment and enhanced the smooth transition of graduate nurses into critical care. Through mutual collaboration between education and service, benefits to the health care system were extended. PMID- 1589043 TI - Research: the bridge to collaboration. AB - A faculty-staff research fair was used by a school of nursing and university hospital at a large Southern medical center as a way of promoting collaboration between nursing education and service. The end results were these: a nurse theorist "room" in the school of nursing; development of collaborative studies; subsequent presentation of posters originally prepared for the fair at 12 local, 13 state, six regional, and three national meetings. The overwhelming positive response by participants verified that research could serve as a natural bridge to promote collaboration between research, education, and service. PMID- 1589044 TI - The code of ethics and the role of nurses: an historical perspective. AB - A retrospective on the concept of nursing's code of ethics as it was considered throughout our history. Cianci discusses its importance in the early days and why it has even broader implications in today's troubled times. PMID- 1589045 TI - Rural health screening: a case study in coordination. AB - Collaboration helped a group of health care professionals identify clients' health needs, exchange professional knowledge, offer insight, and plan and implement a health screening program for rural older adults at risk for diabetes mellitus. The authors found collaboration with health professionals to be synergistic and energizing. When nurses with various educational and experiential backgrounds work together, rural clients' needs can be addressed. This project was funded by the American Diabetes Association, Ohio Affiliate. PMID- 1589046 TI - A program design for preceptor training. AB - Training clinical preceptors in the subtleties of clinical teaching is essential to the success of precepted orientations. This paper presents a program design for the preparation of these preceptors. Emphasis is on the assumptions underlying the program, program content, and evaluation. PMID- 1589047 TI - ['It is only a hernia']. PMID- 1589048 TI - [The patient's request: an important determinant for quality of medical care]. PMID- 1589049 TI - [Management of the resistance problem by using an antibiotic protocol]. PMID- 1589050 TI - [Rheumatoid arthritis and anemia; various aspects concerning prevalence, pathogenesis, diagnosis and therapy]. PMID- 1589051 TI - [Hemoglobinopathies in The Netherlands; is screening of foreign women desirable?]. PMID- 1589052 TI - [Good results of cyclophosphamide in steroid toxicity in the treatment of nephrotic syndrome caused by minimal-lesion glomerulopathy in childhood]. AB - The effect of cyclophosphamide therapy was evaluated in the treatment of children with nephrotic syndrome due to minimal lesions. Most of the children, 37 out of 43, presented with frequent relapsing nephrotic syndrome. Cyclophosphamide was given in a dose of 3 mg/kg body weight/day for a period of 8 weeks. Two patients received two courses, one patient received three courses. Only one patient, who was steroid-resistant, did not respond to cyclophosphamide therapy (therapy was, however, stopped after 3 weeks because of haemorrhagic cystitis). 57% of the patients were still in remission after 18 months (n = 37) and 50% after 30 months (n = 34). A haemorrhagic cystitis developed in 3 patients and leucopenia in 2 patients. From this study, which confirms data reported in literature, it can be concluded that cyclophosphamide has a beneficial effect in children with minimal lesion nephrotic syndrome and steroid toxicity. PMID- 1589053 TI - [Non-urgent patients in a non-traumatology Emergency Service; general aspects and screening for psychiatric disorders]. AB - The Emergency Department is used by a rather large number of patients with a non urgent condition. It is unknown whether the request for medical assistance for non-urgent conditions is partly due to the presence of a mental disorder. We conducted a cross-sectional study of 711 patients of a non-traumatic Emergency Department. The prevalence and determinants of non-urgent conditions and of mental disorders of non-urgent patients were studied. Of all patients, 31% had a non-urgent condition. Self-referrals and young adults more often had a non-urgent condition. However, in our study only 17% of all patients were self-referred. The prevalence of a score greater than or equal to 5 on the general health questionnaire (GHQ), an indication of the presence of a mental disorder, in the non-urgent patients was 59%. Non-acute symptoms, life events, the use of psychotropic drugs and alcoholism were determinants for a high GHQ score, but their specificity was low. It is advised to include questions concerning mental disorders in the medical interview of non-urgent patients. PMID- 1589054 TI - [Medical activities under adverse conditions. Memisa Medicus Mundi]. PMID- 1589055 TI - [Social support following induced abortion for genetic indications: experiences of the women concerned and their partners]. PMID- 1589056 TI - [Self mutilation]. PMID- 1589057 TI - [Errors in literaure references in the Nederlands Tijdschrift voor Geneeskunde]. PMID- 1589058 TI - [Classification of fibromyalgia: criteria of the American College of Rheumatology]. PMID- 1589059 TI - [Evaluation of bacterial resistance to pefloxacine after prolonged use in resuscitation]. AB - In an overall of the value of an antibiotic it is important to take into account the onset of bacterial resistance in addition to its immediate clinical effects since the former can render an otherwise efficacious antibiotic obsolete within a short space of time. We studied two groups of intubated patients with pneumonia infections during two different periods in 1990: January-June and October December; each patient was treated with pefloxacin 400 mg twice a day i.v. for 6 days on the basis of an antibiogram carried out on tracheobronchial secretion; at the end of that period patients were clinically evaluated and a second bacteriological test was performed. It was found that the percentage of pefloxacin-resistant bacterial strains did not increase significantly after this antibiotic had been used for a year for pneumonia infections (from 27.5% to 33%). The appearance of bacterial resistance at the six-day treatment cycle was similar in both groups (19% and 22%). Of all the bacterial strains, Pseudomonas aeruginosa showed the greatest tendency to become resistant. PMID- 1589060 TI - [Validity of the V/Q index in the monitoring of critical patients]. AB - The Authors have controlled the validity of VQI to quantify pulmonary shunt (Qs/Qt). The survey involved (group A) patients who had undergone major surgery and (group B) patients hospitalized in ICU for cardiorespiratory failure. Four subgroups were identified in both the groups according to different values of SaO2. A good correlation, already described by Rasanen, was comproved in the groups and subgroups. However a progressive reduction of the coefficient of correlation from the lower to the higher values of SaO2 was noted. Finally the differences observed between group A and group B, are supposed to be dependent on a greater variability of haemoglobin, in the surgical group, in relation to the time of evaluation. PMID- 1589061 TI - [Hypokalemic myopathy. Our experience at an intensive care unit]. AB - Disturbances of potassium homeostasis are frequently iatrogenic: some drugs, especially diuretics, are sometimes taken without proper electrolyte control and replacement; this can lead to more or less severe hypokalemic states. After some physiopathologic remarks, the Authors report their experience with four patients admitted for severe hypokalemia; the clinical picture was always quite typical: severe muscle weakness (even quadriparesis), cardiac rhythm abnormalities, metabolic alkalosis. A reliable diagnostic tool is muscle biopsy that shows aspects of vacuolar myopathy. PMID- 1589062 TI - [How many interscalene blocks are there? Reflections on 109 cases studied with various techniques]. AB - The effects of interscalene block were studied on 109 patients undergoing upper extremity elective orthopaedic surgery. Blocks were performed in a non-randomized manner with three different techniques, the site where anaesthetic solution was injected being the main distinguishing mark. The anaesthetic solution was injected into the interscalenic compartment both in the case of patients where classic technique had been carried out and in the group where the nerve stimulator had been used. In the "double needle" technique group, on the contrary, the anaesthetic solution was injected close to the vertebral column. The spread of analgesia involves the caudal portion of the cervical plexus and the cranial portion of the brachial plexus, but with the cervical plexus is almost certain to be involved, the brachial is not. Block outcome was related to the surgical procedure (surgery or orthopaedic manipulation), the site of surgery, paraesthesia elicitation, prolonged surgery and height, weight, age and sex of patients. Results also different according to the technique used. When the anaesthetic solution was injected close to the vertebral column analgesic cover was more widespread and lesser amounts of anaesthetic needed. When the block was performed within the interscalenic compartment, the analgesic cover was usually restricted to the area supplied by the primary superior trunk of the brachial plexus. The different results were explained by the presence of fibrous sheaths within the interscalenic compartment limiting spread of the anaesthetic, which are absent close to the vertebral column. Therefore two types of interscalene block were postulated: an intrascalene or troncular block within the interscalenic compartment and a radicular or paravertebral block close the vertebral column. PMID- 1589063 TI - [Propofol and alfentanil in total intravenous anesthesia]. AB - We studied 22 patients undergoing total intravenous anaesthesia for both abdominal and superficial surgery. Anaesthesia has been induced and maintained with propofol (1 mg/kg in 20 seconds; 10 mg/kg/h for 10 minutes; 8 mg/kg/h for 10 minutes; 6 mg/kg/h until the end of the operation) and alfentanil (15 mg/kg before the induction and boli of 10-30 mg/kg in the presence of insufficient surgical analgesia). All the patients have been intubated after the administration of vecuronium 0.1 mg/kg, and artificially ventilated with air and oxygen (FiO2 0.4). We observed: 1) haemodynamic stability after the intubation and during surgery; 2) easy control of surgical analgesia; 3) early postoperative recovery, with no correlation with the doses of propofol and alfentanil; 4) absence of postoperative respiratory depression; 5) intraoperative amnesia; 6) low incidence of postoperative side effects. We conclude that, by virtue of the pharmacokinetic characteristics of propofol and alfentanil, most limitations of total intravenous anaesthesia have been overcome. PMID- 1589064 TI - [Total intravenous anesthesia with propofol-fentanyl. Experience with elective operations in plastic surgery]. AB - The Authors evaluated a total intravenous anesthesia with propofol and fentanyl in patients who underwent elective plastic surgery. Main hemodynamic parameters resulted particularly stable, and the awakening times which resulted brief and independent from the anesthesia duration have been measured. PMID- 1589065 TI - [Closed circuit inhalation anesthesia. Consumption and cost]. AB - Closed circuit anaesthesia (CCA) and minimal flow anaesthesia diminish inhalatory anaesthetic consumption. Consumption of inhalatory anaesthesia was calculated using two different techniques: CCA and "non rebreathing" system. Costs were compared on the basis of the official list price. The CCA allowed for reduced consumption at lower costs. The resulting annual savings are equal to one third of the total price of the whole apparatus with its complementary monitoring and control systems. PMID- 1589066 TI - [Intravenous anesthesia during oocyte harvesting for in vitro fertilization. Description of a method]. AB - The Authors describe their anaesthetic technique with a continuous i.v. infusion of propofol in female patients undergoing oocyte retrieval during in vitro fertilization. With this technique a great stability of the haemodynamic and respiratory parameters was recorded, adverse effects were never observed and every patient quickly regained a normal psychomotor performance. This operation can be, therefore, carried out in ambulatory regimen with complete safety and good acceptability from the patients. PMID- 1589067 TI - [Anesthesia in percutaneous discectomy by the Onik's technique]. AB - The type of anaesthesia used in percutaneous discectomy, a new technique for treating slipped disc, is described. The personal series consist of 960 patients. In 768, local anaesthesia by infiltration of the anatomical trajectory was used as a follow-up to nucleotome. In the rest, general anaesthesia was used. Conclusion are drawn from the comparison. PMID- 1589068 TI - [Nasocardiac reflex evoking during rhinoseptoplasty. Description of a clinical case]. AB - We report a case of nasocardiac reflex which occurred during a septorhinoplasty. Management and preventive treatment is briefly discussed. PMID- 1589069 TI - [Intraoperative changes in aerobic and anaerobic metabolism as prognostic index in interventions of massive hepatic resection]. AB - This study was conducted on 10 patients with primitive or metastatic liver tumors, scheduled for massive liver resections, in order to search for evidence of the existence of intraoperative prognostic indexes having a bearing upon postoperative survival. The following parameters were measured in every patient: HR, MAP, CVP, MPAP, WP, SVR, PVR, CI, DO2, VO2, BE, before the anhepatic period (A), during anhepatic period (B), 30' (C), and 60' (D) after liver reperfusion, holding constant Hct, body temperature, ETCO2, FiO2, anesthetic depth, and the degree of muscular relaxation. The patients were later divided into two groups: 1, nonsurvivors in the postoperative period (4 patients) due to MOF; 2, survivors (6 patients). The values of the measured parameters of the two groups were statistically evaluated at each of the above intervals, and within each group with respect to time A, taken as a control. No significant variations were found in HR, MAP, CVP, MPAP, WP, SVR, PVR, CI, and DO2. The VO2 diminished in both groups during the anhepatic period (B) (p less than 0.0025). In group 1 (nonsurvivors) the VO2 diminished after the reperfusion (p less than 0.0025), while in group 2 (survivors) VO2 rapidly resumed its initial values (n.s. 30' and 60' after the reperfusion). In the nonsurviving patients metabolic acidosis developed, with significant reductions of BE (p less than 0.0025) during times C and D, occurring simultaneously with the reduction of VO2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589070 TI - [Anesthesia with continuous infusion of propofol in myasthenic patients]. AB - Anaesthesia with atracurium, fentanyl, and continuous intravenous infusion of propofol in two myasthenic patients is described. There were no intra and postoperative problems and operative conditions were considered excellent. This technique offers a safe alternative to inhalational anaesthesia for patients with myasthenia gravis. Monitoring of neuromuscular function is mandatory. The use of atracurium in myasthenic patients and the influence of propofol on neuromuscular transmission are discussed. PMID- 1589072 TI - [Locoregional anesthesia for surgical arthroscopy of the knee]. AB - A new technique for regional anaesthesia for arthroscopy of the knee is presented. The method includes sciatic nerve block according to the technique proposed by Labat, through a posterior approach and the block of the femoral and lateral cutaneous nerves using a single anterior approach. Results obtained in 30 patients are presented: they include good stability of the cardiovascular and respiratory parameters, high efficiency and duration of anaesthesia resulting in a satisfactory surgical procedure. PMID- 1589071 TI - [Clebopride in premedication in ambulatory interventions in general anesthesia]. AB - The authors examine the antiemetic effects of 1 mg clebopride administered iv after surgery, vs a placebo, by making a double blind randomized study on two groups of 40 women comparable by age and weight. The 2 groups of outpatients, admitted for short gynecological surgery, underwent diagnostic uterine curettage. They were anaesthetized with a cocktail of 2.5 mcg/kg fentanyl and 0.25 mg/kg ketamine, on spontaneous respiration. Nausea, vomiting and the other side effects were evaluated 3-6 hours after surgery. Statistically, clebopride proved more effective than placebo against nausea and vomiting (P ranging between 0.05-0.01), with no relevant side effects. PMID- 1589073 TI - [The use of the Bullard laryngoscope]. AB - Eighty patients were submitted to orotracheal intubation with adult bullard laryngoscope blade. Use and advantages are described, especially in difficult intubation. PMID- 1589074 TI - [Study of the peridural space with "elastic" liquid mandrel]. PMID- 1589075 TI - [Inhalation anesthesia in low-flow systems. Clinical evaluation of the kinetics of isoflurane in induction phase]. AB - Closed circuit and low flow anaesthesia offer numerous advantages such as reduction of gas consumption, low cost, and less pollution in both the operating theatre and the environment. These procedures also offer increases in inspired gas humidity and temperature. However the time needed to attain the alveolar concentration MAC 95, is too long. Prefilling the whole circuit, the bellow and the bag with anaesthetic vapours shortens that time without overdosage. PMID- 1589076 TI - [Transfusional needs and blood saving strategies during orthotopic heart transplantation]. AB - It is difficult to evaluate transfusional needs during cardiac surgery. One hundred fifty patients undergoing orthotopic cardiac transplantation were divided into two groups (A and B) according to the blood saving strategies. (Group A: no important saving strategies; group B: all blood saving techniques utilized). A low blood, plasma and platelet consumption was observed, with good clinical results, in group B. During orthotopic cardiac transplantation, it would be suitable to use all the saving transfusional blood strategies and a correct use of hemocomponents as during all cardiac surgery. PMID- 1589077 TI - [Hypoxia and oxygen content during dialysis]. AB - In a study of 72 patients treated with acetate and bicarbonate dialysis, the Authors verified if hypoxic hypoxia caused by dialysis depends on a deficit in oxygen content with an inherent risk of tissue hypoxia. PO2uv (uncompensated venous oxygen partial pressure) and CQ (cardiac compensation factor) derived from the oxygen absorption curve were studied by a new Ole Siggard-Andersen algorithm. The results do not show a risk of tissue hypoxia in the postdialytic period. PMID- 1589078 TI - [Comparison of 2 techniques of anesthesia induction in modern closed-circuit anesthesia]. AB - The application of low flow anesthesia goes back already for more than 65 years when Ralph Waters introduced and applied cyclopropane with a very simple canister technique. The guide-lines for the clinical use of the closed circuit anesthesia were published in Chicago and Los Angeles by Professor Lin and Professor Lowe 15 years ago. We examined and followed these procedures on a modern anesthesia machine and easily achieved a good clinical performance. Our results were consistent with the modern anesthesia standard in closed circuit t.i.: economical benefits, environment savage of waste gases, heat production and humidification and last but not least in both techniques a quick anesthesia plane on 10-12 minutes that was consistent with theoretical considerations. PMID- 1589079 TI - [Hormonal changes during surgical stress. Comparison of isoflurane anesthesia, neuroleptanalgesia, propofol]. AB - Our purpose is to verify if different techniques of general anaesthesia can modify the patient's hormonal response to surgical stress. For this extent 35 patients, undergoing Cottle's septoplasty, were randomly divided into three groups, treated using different anaesthesiological techniques (forane, NLA and propofol). No variation was noted between the three groups regarding cortisol increments, while the patients, in whom forane was used for anaesthesia maintenance, manifested less significant variations in prolactin levels. This may be indicative of good forane protection for surgical stress. PMID- 1589080 TI - [Pharmacologic prevention of Mendelson syndrome. A controlled clinical trial]. AB - This controlled study considers the effect of ranitidine, both alone and in association with metoclopramide, on the acidity and volume of the gastric content of 75 patients requiring caesarean section. Ranitidine, when used alone (50 mg intravenously 30-60 minutes before the operation) significantly reduced (p less than 0.01) the acidity (pH greater than 2.5) and the volume (less than 25 ml) of the gastric content of the patient thus treated. Ranitidine in association with metoclopramide may also reduce the pH and the volume, but did not show any significant statistical differences when compared with the use of ranitidine alone. PMID- 1589081 TI - [Biliary lithiasis in the elderly patient. The role of the surgical intervention]. PMID- 1589082 TI - [The surgical procedures of biliary drainage in the lithiasis patient. When and how?]. PMID- 1589083 TI - [Lithiasis of the main biliary tract. Treatment evolution over 23 years]. PMID- 1589084 TI - [The combined treatment by chemical litholysis and lithotripsy of so-called difficult bile duct calculi]. PMID- 1589085 TI - [Reflux esophagitis: a study of its etiology and physiopathology as a premise to therapeutic choice]. PMID- 1589086 TI - [The surgical treatment of gastroesophageal reflux in the adult. The results and prospects]. PMID- 1589087 TI - [The surgery of gastroesophageal reflux: the grounds for a choice]. PMID- 1589088 TI - [Jejunal-ileal atresia]. PMID- 1589089 TI - [Transsphincteral anorectal malformations]. PMID- 1589090 TI - [Childhood constipation. Radionuclide transit times]. PMID- 1589091 TI - [Ulcerative rectocolitis. The problems in childhood]. PMID- 1589092 TI - [The complications of ulcerative rectocolitis]. PMID- 1589093 TI - [Colonoscopic screening in ulcerative rectocolitis. The authors' own experience]. PMID- 1589094 TI - [Ulcerative colitis]. PMID- 1589095 TI - [Ulcerative colitis: the ultrastructural and differential diagnostic aspects]. PMID- 1589096 TI - [The surgical therapy of ulcerative rectocolitis. Our experience]. PMID- 1589097 TI - [Blood recovery and autotransfusion within integrated transfusion systems during liver transplantation. The authors' own experience]. PMID- 1589098 TI - [Intraoperative blood recovery in cardiovascular surgery]. PMID- 1589099 TI - [Acute isovolemic hemodilution and saving of the blood in surgery]. PMID- 1589100 TI - [The indications for hemodilution and autotransfusion in anesthesiology and intensive therapy]. PMID- 1589101 TI - [The physiopathology of acute intentional normovolemic hemodilution (AINH)]. PMID- 1589102 TI - [Strategies for avoiding or reducing the use of homologous blood in heart surgery]. PMID- 1589103 TI - [The priority status in the treatment of the multiply injured]. PMID- 1589104 TI - [Priorities in the treatment of the multiply injured. The experience of the Piedmont Trauma Center]. PMID- 1589105 TI - [The surgical strategy in massive hemoperitoneum]. PMID- 1589106 TI - [Riedel's thyroiditis. Its nosography and surgical problems]. PMID- 1589107 TI - [Our surgical experience in thyroiditis]. PMID- 1589108 TI - [The diagnosis of thyroiditis]. PMID- 1589109 TI - [The repair of the vermilion border with an orbicular musculocutaneous flap]. PMID- 1589110 TI - [Fasciocutaneous flaps]. PMID- 1589111 TI - [Composite flaps in the reconstruction of the cervicofacial area]. PMID- 1589112 TI - [Our experience in reconstructive microsurgery with free flaps]. PMID- 1589113 TI - [The functional results of antireflux technics]. PMID- 1589114 TI - [The surgical treatment of gastroesophageal reflux (GER)]. PMID- 1589115 TI - [The surgical therapy of alkaline esophagitis. The authors' own experience]. PMID- 1589116 TI - [The evolution of the treatment of esophagitis due to acid reflux. Our experience]. PMID- 1589117 TI - [Peptic esophagitis]. PMID- 1589118 TI - [The state of the art of the therapy of peptic ulcer: hemorrhage]. PMID- 1589119 TI - [The state of the art of the therapy of peptic ulcer]. PMID- 1589120 TI - [Perforated peptic ulcer: the current treatment]. PMID- 1589121 TI - [Totally implantable systems in colorectal tumors. The locoregional chemotherapy of hepatic and peritoneal metastases]. PMID- 1589122 TI - [Mechanical and pressure suturing devices: the preliminary results of a comparative endoscopic study]. PMID- 1589123 TI - [A new approach in the treatment of esophageal varices in the cirrhotic patient]. PMID- 1589124 TI - [The UKL-60 at 30 years]. PMID- 1589125 TI - [An analysis of so-called "disease resumptions" in operated bronchogenic cancer in homogeneous case histories]. PMID- 1589126 TI - [The role of surgery in the prevention of pulmonary thromboembolism]. PMID- 1589127 TI - [Mechanical suturing devices in bronchopulmonary surgery]. PMID- 1589128 TI - [Uveitis and systemic diseases]. AB - The uveal tract, although comprising three anatomic sections such as the iris, the ciliary body and the choroid, may be regarded as a single functional unit, and is easily affected by several pathogenic agents that may act on either infectious, toxic and immune basis. Since such inflammatory stimuli do not usually locate primarily in the eye but rather elsewhere in the body, uveitis is often associated with systemic diseases. The Authors deal with several diseases frequently associated with anterior or posterior uveal inflammation, such as Behcet's disease, Vogt-Koyanagi-Harada's syndrome, Reiter's syndrome, juvenile rheumatoid arthritis, ankylosing spondylitis, sarcoidosis, Sjogren's syndrome, ulcerative colitis, psoriasis, tuberculosis and syphilis. PMID- 1589129 TI - [Coin lesions: 5 years of percutaneous needle aspiration]. AB - 197 patients with either malignant (No. 175) or infections (No. 22) chest coin lesions had lung aspirations using fine-needles, 18 to 22 gauge. All the patients previously had flexible fiberoptic bronchoscopy with negative results. A positive diagnosis of malignancy was established in 138 (70%), with identification of cell type in 51 (37%), and of infectious disease in 11 (50%). The procedure's sensitivity for malignant lesions was 79.3% and the specificity was 96.5%. Complications were minimal (hemoptysis and pneumothorax), although some patients had COPD and hypoxemia. PMID- 1589130 TI - [Pneumothorax in AIDS]. AB - A total of 237 patients with AIDS have been observed in the infectious Disease Division of the United Hospitals of Bergamo during the past six years. Five patients (4.21%), suffering from TB and PCP, revealed PNX which was characterised by being bilateral and recurrent; it was a concomitant cause of death in 2 patients. The complications which occurred included acute pulmonary heart, pulmonary edema due to reexpansion and irreversible shock. PMID- 1589131 TI - [Evaluation of the effects of reduced glutathione in subjects with acquired and congenital changes in heme biosynthesis]. AB - In order to evaluate the possible therapeutical effects of reduced glutathione in subjects affected by acquired or congenital heme biosynthesis alterations, two groups of subjects have been considered: the first, of 5 subjects with abnormal lead absorption, the second of 10 patients suffering from porphyria cutanea tarda (PCT). The drug was administered i.v. at the dosage of 600-1200 mg for a variable period of 3-5 days in the first group, for 7-10 days in the patients with PCT. In the lead-exposed subjects an increase in the activity of ALA-dehydratases enzyme was observed, with a decrease in the urinary excretion of delta-aminolevulinic acid, and a decrease in the percentage of urinary coproporphyrins as well. In the patients with PCT, after the therapy, a relevant reduction of urinary excretion of porphyrins, prevalently uro- and heptaporphyrins, was noticed. The results of this preliminary study suggest that glutathione can exert an effect of "normalization" on heme biosynthesis when altered in acquired and/or congenital conditions. PMID- 1589132 TI - [Sequential nimodipine-reduced glutathione treatment in alcoholic abstinence syndrome. Preliminary experience]. AB - Alcohol abstinence syndrome (AAS) occurs in alcohol dependent patients a few hours after ceasing to drink, first in the form of gastrointestinal and dysvegetative signs, then with the involvement of neurological functions. The results obtained in 15 patients selected according to DSM III criteria, treated with nimodipine (calcium entry blocker) in the acute phase and with reduced glutathione in the subacute phase are presented. All patients who, during treatment, did not take other drugs, showed a definite, fast improvement in symptoms, especially in neurovegetative symptoms. Administration of nimodipine, which seems capable of reducing the catecholaminergic drive, was very well tolerated. Treatment with reduced glutathione is justified by the fact that the inadequate intake of alcohol is responsible for liver changes and, particularly, for a significant reduction in liver levels of glutathione, a condition that makes the cell more exposed to attack on the part of substances that activate lipoperoxidation processes. The results obtained seem to confirm a protective action on the part of reduced glutathione. PMID- 1589133 TI - [Chemotherapy and thymostimulin in the treatment of advanced-stage breast neoplasms]. AB - In this study, we have evaluated certain haematologic and immunologic parameters in two advanced disease patient groups treated with chemotherapy (CMF schedule)+thymostimulin or chemotherapy alone, respectively. Statistical analysis of the data does not reveal any significant difference between the two patient groups. In our opinion, however, the administration of thymic hormone seems to protect the marrow crasis and, as a consequence, to obtain a lower incidence of side effects and respect of chemotherapeutic schedule. PMID- 1589134 TI - [Effects of hydration on plasma concentrations of methotrexate in patients with osteosarcoma treated with high doses of methotrexate]. AB - High dose of methotrexate (HDMTX) with leucovorin rescue requires over hydratation to avoid nephrotoxicity; nevertheless the relationship between hydratation and plasma MTX levels is unknown. We compared the effects of two different types of hydratation (2 lt/m2 vs 1.5 lt/m2) on plasma MTX levels in two groups of patients with osteosarcoma of the extremities and treated with HDMTX (8 g/m2 IV). Samples were obtained at the end of infusion of MTX and 14 and 38 hours after the start of MTX infusion. At the end of infusion of MTX the medium plasma MTX levels proved significantly higher in the group with low hydratation than in the group with high hydratation (585.5 microns/l vs 427.7 microns/l P less than 0.001). The values obtained at 14 and 38 hours, did not show significant differences. No significant differences were seen between the two groups in term of late elimination of MTX and correlated toxicity. These data show that a low hydratation regime allows higher plasma MTX levels at the end of infusion of HDMTX and does not increase the incidence of late elimination of MTX compared to a high hydratation regime. PMID- 1589135 TI - [L-sulpiride versus metoclopramide in functional dyspepsia: a randomized double blind study]. AB - Fifty patients suffering from functional dyspepsia have been treated in a double blind study either with 1-sulpiride (75 mg die per os) or with metoclopramide (30 mg die per os) for 30 days. The frequency and severity of the symptoms in the two patient groups were similar. The administration of either drug was followed by a reduction of the symptoms, but 1-sulpiride was more effective on nausea, headache, pyrosis, epigastric pain, and showed an earlier effect than metoclopramide in inducing total regression of symptoms. PMID- 1589136 TI - [A study carried out in 1989 at the Sant'Antonio Hospital of Ovada on food poisoning in personnel handling and selling food products and drinks]. AB - The search for Salmonella spp in the faeces and of Staphylococcus aureus in pharyngeal pads during examinations for the renewal of the Medical Fitness Booklet, leads to a number of considerations of a technical-health and economic nature. Whereas the identification of Staphylococcus aureus is fairly straightforward, that of salmonella in the faeces is not so easy. Doubtful results are commonplace and bacteria are often found with features similar to salmonella; this means extra examinations with commitment of time, money etc. PMID- 1589137 TI - [Massive myoglobinuria and blood hyperenzymes after mild physical exercise in a healthy young man]. PMID- 1589138 TI - [Familial Mediterranean fever and electroencephalographic changes. A clinical case]. AB - The Authors describe the case of a non-Hebrew Italian girl suffering from short lasting fever episodes, associated with abdominal colic, since the age of 3. The occurrence of acute arthrosynovitis during the last episode, at 12 years of age, clinically confirms the diagnosis of familial mediterranean fever, as previously supposed. The increase in urinary coproporphyrins, with normal values of delta aminolevulinic acid and porphobilinogen poses the problem of the differential diagnosis between hereditary coproporphyria and secondary coproporphinuria. The importance of this case lies in the presence of electroencephalographic alteration since the first years of life, suggesting a temporal epilepsy for which the patient was at length submitted to anti-epileptic treatment. Electroencephalographic alterations, of different type and uneasy interpretation, are described in the literature with a frequency which does not seem accidental. Renal biopsy does not show amyloid, nor the RMN reveals cerebral abnormalities. The anti-epileptic therapy being withdrawn, the patient was treated with daily administrations of colchicine (1 mg/die); 18 months after, she is disease free. PMID- 1589139 TI - [Neurological manifestations in Marfan's syndrome. A critical review and presentation of a case]. AB - Marfan's syndrome is a heritable disorders of the connective tissue known mainly for its skeletal, cardio-vascular and ocular changes. A recent case of intracranial hematoma in a girl with Marfan's syndrome, hyperkyphosis and scoliosis led the Authors to investigate neurological problems in this syndrome, finding in the literature a greater number of reports than expected. PMID- 1589140 TI - Whole-cell patch-clamp recordings from respiratory neurons in neonatal rat brainstem in vitro. AB - Whole-cell recordings were obtained from respiratory neurons by applying patch clamp techniques in the en bloc medulla of in vitro neonatal rat brainstem-spinal cord preparations. Stable voltage-clamp recordings of excitatory or inhibitory synaptic drive currents and current-clamp recordings of spike discharge of inspiratory and expiratory neurons could be maintained for periods of 1-2 h. Parameters of whole-cell recording, including membrane seal resistances and series resistances, obtained in the en bloc medulla were similar to those obtained in corresponding regions of thin slices where neurons were directly visualized to optimize conditions for whole-cell patch clamp. PMID- 1589141 TI - Differential effects of mild hypoglycemia on proximal and distal retinal structures in man as revealed by electroretinography. AB - We investigated the effect of blood glucose concentration on the human visual system. Blood sugar levels were modified by intravenous infusion with insulin or glucose. Luminance electroretinograms (L-ERG) were elicited with colored flashes, and pattern ERGs (P-ERG) evoked by checkerboard reversal stimuli were obtained simultaneously with cortical visually evoked potential (VEP). With glucose levels above or below the baseline values the b-wave of the L-ERG was significantly larger than with normal glucose levels, whereas the P-ERG displayed maximal amplitudes at normal glucose levels and a significant amplitude decrease with glucose levels below or above normal. Since L-ERG and P-ERG activity is generated by different retinal structures, this indicates that distal and proximal layers of the human retina are affected differently by changing glucose levels probably due to regional differences in retinal circulation. PMID- 1589142 TI - A test for increased lethality in land snails exposed to 60 Hz magnetic fields. AB - A recent report suggested that exposures of land snails to 0.1 mT, 60 Hz magnetic fields for periods of 48-120 h increase mortality levels by 2-10 times. In direct experimental tests, we were unable to confirm this effect. PMID- 1589143 TI - GM1 ganglioside reduces ischemia-induced excitatory amino acid output: a microdialysis study in the gerbil hippocampus. AB - The effects of transient forebrain ischemia on the extracellular concentration of the excitatory amino acids glutamate and aspartate were studied in the gerbil hippocampus using microdialysis. Bilateral carotid occlusion (8 min) increased glutamate and aspartate concentration in the dialysate by 3- to 8-fold. This increase lasted 20-30 min. When the animals were pretreated with GM1 ganglioside (30 mg/kg/day, i.p., for 3 days), the ischemia induced increase of excitatory amino acids in the dialysate was significantly reduced. The results are in line with the hypothesis that systemic GM1 ganglioside administration may reduce ischemia-induced brain damage. PMID- 1589144 TI - Prolongation of magnetic resonance T2 time in hippocampus of human patients marks the presence and severity of Alzheimer's disease. AB - Spin-spin relaxation time (T2) was measured in the hippocampal formation, thalamus, and cortical white matter in 13 patients with probable Alzheimer's disease (AD), 11 elderly normal individuals, 23 healthy young persons, and 9 subjects diagnosed with multi-infarct dementia. A 0.04 tesla magnetic resonance scanner was used. Hippocampal T2 values for all AD patients exceeded those of any non-AD individual, regardless of age or dementia due to infarction. Further, these T2 values were highly correlated (+ 0.96) with the severity of functional and cognitive impairment of the AD patients. This T2 prolongation was not observed at the other sites examined. These results suggest that hippocampal T2 prolongation may provide a specific marker by which AD pathology can be detected, characterized, and followed in vivo. PMID- 1589145 TI - A new peptide of the oxytocin/vasopressin family isolated from nerves of the cephalopod Octopus vulgaris. AB - An oxytocin/vasopressin-immunoreactive peptide was isolated from nerve terminals of the 'neurosecretory system of the vena cava' in octopus. It was purified by HPLC combined with a RIA for oxytocin. Characterization of the peptide by automated Edman degradation, plasma desorption mass spectroscopy, enzymatic treatment and coelution experiments resulted in the structure: Cys-Tyr-Phe-Arg Asn-Cys-Pro-Ile-Gly-NH2, a nonapeptide with a molecular weight of 1070 Da and a 1 6 disulfide bond. This cephalopod neuropeptide, here called 'cephalotocin', exhibits 78% sequence homology with the vertebrate neurohypophysial hormone mesotocin and clearly belongs to the oxytocin/vasopressin family of vertebrates, confirming the high conservation of this peptide family. PMID- 1589146 TI - Repeated ethanol administration decreases prodynorphin biosynthesis in the rat hippocampus. AB - The effect of single and repeated (19 days) intragastric ethanol administration on prodynorphin mRNA and alpha-neoendorphin levels in the hippocampus of the rat was studied using in situ hybridization and RIA methods, respectively. Single ethanol administration had no effect on either of these two parameters. Repeated ethanol administration decreased both immunoreactive (ir) alpha-neoendorphin (by ca. 37%) and prodynorphin mRNA (by ca. 57%) levels. Two days after the last dose of ethanol no changes in the ir-alpha-neoendorphin tissue content were found, whereas the level of prodynorphin mRNA remained decreased (by ca. 44%). These results suggest that repeated ethanol evokes a long-lasting decrease in the biosynthesis of hippocampal prodynorphin, this effect that may play some role in the ethanol-induced deficiency of neuronal functions. PMID- 1589147 TI - Glial fibrillary acidic protein and vimentin immunohistochemistry in the posterior rhombencephalon of the Iberian barb (Barbus comiza). AB - The gustatory centers (vagal lobes and facial lobe) and the tegment of the posterior rhombencephalon of the Iberian barb (Barbus comiza) have been studied using anti-glial fibrillary acidic protein (anti-GFAP) and anti-vimentin immunohistochemical techniques. GFAP immunoreactivity was found in the tegment and in a part of the vagal lobes while vimentin immunoreactivity was located in the tegment. Two immunopositive cell types were found: ependymocytes and radial astrocytes. Since the distribution of GFAP in the barb rhombencephalon corresponds with zones previously described as cholinergic, the GFAP immunopositive radial astrocytes might be involved in acetylcholine metabolism. PMID- 1589148 TI - Endothelin-3 stimulates the release of catecholamine from cortical and striatal slices of the rat. AB - Endothelin-3 (ET-3) evoked the release of dopamine/noradrenaline from cortical slices and dopamine from striatal slices in a concentration-dependent manner. This action peaked slowly and was long-lasting in real-time monitoring, being different from the high K(+)-evoked response. The striatal response to 10 microM of ET-3 was reduced by extracellular Ca2+ depletion to 40% of control and by Ca2+ antagonists, especially nifedipine and flunarizine, to 40% of control. Our findings suggest that ET has a physiological significance in the brain as a neuromodulator for catecholaminergic transmission. PMID- 1589149 TI - Anomalous effect of mazindol on dopamine uptake as measured by in vivo voltammetry and microdialysis. AB - The effect of mazindol on the dopamine (DA) uptake system in the rat striatum was studied by in vivo voltammetry and microdialysis. An increase in the maximal uptake rate was observed by voltammetry 30 min after i.p. administration of 1, 5, 10, 15, and 20 mg/kg doses but not after a dose of 25 mg/kg, while stimulated release was enhanced at all doses. The increased maximal uptake is in contrast to increased levels of extracellular DA observed with microdialysis following mazindol administration. This divergence of action is anomalous in the context of current understanding of the DA uptake system. PMID- 1589150 TI - Anterior pretectal nucleus-induced modulatory effects on trigeminal brainstem somatosensory neurons. AB - This study examined the effects of anterior pretectal nucleus (APT) conditioning stimulation on the activity of 92 functionally identified somatosensory brainstem neurons in the trigeminal (V) subnuclei oralis, interpolaris and caudalis of anesthetized rats. Conditioning stimulation inhibited most of the nociceptive neurons and some of the non-nociceptive neurons; facilitation was observed only in some non-nociceptive neurons. These data indicate that the ATP has modulatory effects on both nociceptive and non-nociceptive V somatosensory neurons. PMID- 1589151 TI - Synaptic contacts between CGRP-immunoreactive terminals and enkephalin immunoreactive neurons in the central amygdaloid nucleus of the rat. AB - An immunoelectron microscopic method combined with immunofluorescence double staining was carried out to examine the relationship between calcitonin gene related peptide (CGRP)-like immunoreactive (LI) axon terminals and enkephalin (ENK)-LI neurons in the central amygdaloid nucleus (Ce) of the rat. The latter method showed that many ENK-LI cell bodies are densely surrounded by CGRP-LI axons in the lateral subdivision of the Ce (CeL). After taking fluorescence micrographs, the immunoperoxidase technique was used to examine the CGRP-LI axonal profiles under an electron microscope. CGRP-LI terminals were frequently found to form axo-somatic synaptic contacts with ENK-LI neurons in the CeL. PMID- 1589152 TI - Differences in spike-wave discharges in two rat selection lines characterized by opposite dopaminergic activities. AB - In the present study, 48 h electroencephalographic recordings were made in order to examine the incidence and duration of spike-wave discharges in apomorphine susceptible (APO-SUS) and apomorphine-unsusceptible (APO-UNSUS) lines of an outbred strain of Wistar rats. In comparison with APO-UNSUS rats APO-SUS rats showed significantly more spike-wave discharges, especially during the dark period: both the mesor and the amplitude of the optimal cosine fitted to the data were significantly increased, whereas neither the acrophase nor the period length (24 h) differed. It is suggested that both the relatively low dopaminergic activity of the nigrostriatal fibres and the relatively high dopaminergic activity of the mesolimbic fibres, i.e. two well characterized features of the APO-SUS rats, significantly contribute to the high incidence of spike-wave discharges in these APO-SUS rats. PMID- 1589153 TI - Agonist effects at putative central 5-HT4 receptors in rat hippocampus by R(+)- and S(-)-zacopride; no evidence for stereo-selectivity. AB - The EEG of halothane anaesthetized rats was recorded from an electrode implanted into the hippocampus. In the present study the effect of R(+)- and S(-) zacopride, administered intra-cerebroventricularly, on different frequency bands of the EEG was investigated. Both enantiomers induced similar dose-dependent (5 20 micrograms) increases in all frequency bands. The effects of R(+)- and S(-) zacopride were inhibited by pretreatment with a high dose of ICS 205-930 (1 micrograms i.c.v.), which suggests the involvement of 5-HT4 receptors. The lack of stereo-selectivity of the zacopride enantiomers is in contrast to observations made in in vitro studies. PMID- 1589154 TI - 5-Hydroxytryptamine modulates spike frequency regulation in reticulospinal neurons involved in the control of locomotion in lamprey. AB - To investigate the effects of 5-hydroxytryptamine (5-HT) on reticulospinal neurons involved in the initiation and control of locomotion in lamprey, 5-HT (10 mM) was locally pressure ejected on the dorsal surface of the brainstem during intracellular recordings from identified reticulospinal neurons in the in vitro brainstem-spinal cord preparation. 5-HT induced a reduction of the late afterhyperpolarization (AHP) following the spike due to a reduction of a Ca(2+) activated K+ current. In addition, 5-HT caused a resting membrane hyperpolarization in a proportion of these cells. Due to the 5-HT induced reduction of the AHP, reticulospinal cells, including those that became hyperpolarized by an application of 5-HT, discharged at a higher rate after 5-HT as a response to the same excitatory drive. PMID- 1589155 TI - Dorsal tegmentum kindling in rats. AB - Electrical stimulations were applied daily for 40 days to the dorsal tegmentum in 9 rats through chronically implanted bipolar electrodes. The intensity of current (2 s trains of 50 Hz, 1 ms monophasic square waves) necessary to trigger a full tonic seizure was determined and applied for all further stimulations. Initial stimulations induced a tonic seizure with a low voltage fast electrocorticographic activity. After repeated stimulations, high amplitude spike and wave discharges developed over the cortex, their duration exceeding 50 s at the 40th stimulation. Simultaneously, the tonic seizures evolved into tonic clonic fits with bilateral myoclonias following the tonic phase. These EEG and behavioral modifications persisted for 30 days after the last stimulus. These results demonstrate that kindling may be obtained from brainstem structures. PMID- 1589156 TI - Socioeconomic characteristics of a Dunedin sample of bipolar patients. AB - In order to determine the sociodemographic characteristics of people suffering from bipolar affective disorder, a cohort of hospitalised adult patients was compared with the general New Zealand population. A review of the casenotes of all those treated in Dunedin's psychiatric inpatient facilities between 1 January 1985 and 31 December 1987 identified 50 women and 41 men. Although their age structure did not differ from the general population, more bipolar patients were unmarried, either never married or divorced. These hospitalised bipolar patients held more secondary school qualifications than the average New Zealander but their subsequent employment record was statistically poorer. A majority were social welfare beneficiaries. Often thought to be a relatively benign condition, bipolar affective disorder has serious and destructive influences on marital and occupational function. PMID- 1589157 TI - Streptokinase and lifestyle outcome in survivors of myocardial infarction. AB - Clinical and lifestyle parameters were assessed in 145 patients who were randomised in a double blind study comparing streptokinase or placebo given within four hours of the onset of ischaemic chest pain. Sixty-six percent of patients were in paid employment at the time of their infarct and 79% returned to paid employment. Patients who received streptokinase returned to work 17 days earlier (p less than 0.05) and returned to sport and leisure activities 33 days earlier (p less than 0.05) than those who received placebo. Those who had received streptokinase also tended to leave hospital earlier (0.8 days, p = 0.07). There were no differences in angioplasty or coronary surgery rates or the incidence of reinfarction in the first year (8%). Total community costs were reduced in the patients who received thrombolytic therapy. These findings have important implications in the benefit:cost analysis of thrombolytic therapy. PMID- 1589158 TI - Colorectal cancer--time to reduce the morality. PMID- 1589159 TI - How alert are hospital doctors to alcohol misuse among acute orthopaedic patients? AB - The notes of 100 acute orthopaedic admissions were examined to discover the number of cases in which doctors considered, identified or addressed problems of alcohol misuse. The adequacy with which routine drinking histories were recorded was also examined. Overall, 17.5% of male and 4% of female patients were identified as misusing alcohol; however action was taken in only 36% of these identified cases. Action tended to be taken in cases of chronic alcohol dependency (withdrawal management) or concomitant psychiatric illness (referral to specialist). No action was taken in other cases even when the admission was identified as alcohol related. Admissions identified as alcohol related were significantly more likely (chi 2, p = 0.0002) to have had a previous adult hospital stay compared with admissions not identified as alcohol related. Only 37% of all patients had an adequate routine drinking history recorded. These results corroborate previous research findings and suggest that New Zealand hospital doctors are inconsistent in identifying and addressing alcohol misuse. The results are discussed in the light of current societal norms which condone alcohol misuse. Possible changes in medical school teaching on alcohol are suggested. PMID- 1589160 TI - How long do general practitioners remain in any one location?: Regional and urban size variations in the turnover of foreign and New Zealand doctors in general practice, 1976-90. AB - Studies of doctor location have, for the most part, focused on geographic variations in access to care, rather than the continuity of care provided at different locations. This paper examines regional and city size variations in turnover rates in general practice and shows that they are highest in the southern and most rural regions of New Zealand. However, an unexpected finding was that no significant differences occurred by doctor origin. While more foreign than New Zealand medical graduates have located in rural New Zealand, similar turnover rates between the two groups indicates that their presence has not resulted in any improvement in the continuity of care provided. PMID- 1589161 TI - Ischaemic stroke and intracerebral haematoma in the Waikato Stroke Registry. AB - OBJECTS: to determine the incidence and outcome of ischaemic stroke and intracerebral haematoma in a hospital stroke registry. METHODS: this was a prospective observational study in a base hospital with catchment population of 205,000. We sequentially sampled 195 persons age 60+ admitted to Waikato Hospital with definite or probable ischaemic stroke or intracerebral haematoma. We assessed Barthel activities of daily living (ADL) scores prior to stroke and at days seven, 30 and hospital discharge. We measured mortality at days seven and 30. RESULTS: One hundred and thirty-three of the 195 subjects (68%) had early CT brain scans. Compared to subjects who were scanned, those not scanned were significantly older, more dependent prior to stroke, less likely to be alert at the time of admission and had a higher mortality. Age, prestroke dependency and level of consciousness were independent predictors of scanning in a multiple logistic regression model. Among subjects who had CT brain scans, 12% had intracerebral haematoma and 88% had ischaemic stroke. The group with ischaemic stroke were significantly older, more often alert on admission and had lower mortality than those with intracerebral haematoma. Survivors in both groups had similar functional outcome as measured by Barthel ADL scores. CONCLUSIONS: twelve percent of elderly subjects who had CT scanning following hospital admission for acute stroke syndrome had intracerebral haematoma. This group had a much higher mortality than the remaining 88% with ischaemic stroke. Functional outcome among stroke survivors in both groups did not differ. The incidence of intracerebral haematoma among subjects with CT proven stroke in New Zealand was similar to that found in hospital based surveys in other western countries. PMID- 1589162 TI - Glyphosate herbicide poisoning experience in New Zealand. PMID- 1589163 TI - Paracetamol toxicity in chronic alcohol abusers--a plea for greater consumer awareness. PMID- 1589164 TI - A brief history of anaesthesia in New Zealand. PMID- 1589165 TI - Blood pressure and blood viscosity. PMID- 1589166 TI - Drugs for resuscitation. PMID- 1589167 TI - Who should do renal biopsies? PMID- 1589168 TI - Calcium metabolism in children with lactase deficiency. PMID- 1589169 TI - Iron deficiency. PMID- 1589170 TI - Silicone breast implants and cancer. PMID- 1589171 TI - SPPS and hypotension. PMID- 1589172 TI - Akathisia associated with carbamazepine therapy. PMID- 1589173 TI - Dementia and prime ministers. PMID- 1589175 TI - Nonpayment for reports. PMID- 1589176 TI - Transport of radioactive material by road. PMID- 1589174 TI - Tuberculous peritonitis and ultrasound. PMID- 1589177 TI - Comparison of instruments for dual-energy X-ray bone mineral densitometry. AB - While bone mineral densitometry has become a common laboratory test, it is important to pay attention to the compatibility of the results from different instruments. In this study results from three commercially available bone densitometers are compared using both patient and phantom studies. Overall correlation between instruments was good but there were systematic discrepancies in the results. The three instruments provided bone mineral density (BMD) values that differed by as much as 13.5% due to differences as large as 6% in bone mineral content and as large as 7% in bone area. Thus, the BMD values obtained from different manufacturers' instruments are not directly comparable. PMID- 1589178 TI - Determination of bone mineral content in the heel bone using a gamma camera. AB - An easy to use and low cost technique for determination of the bone mineral content in the heel bone using an unmodified gamma camera is described. The method uses two small flood phantoms with 125I and 99Tcm, respectively. The precision, when measured on 12 healthy volunteers, was 2.1% and a long-term reproducibility in vitro of 1.8% was obtained on phantoms. PMID- 1589179 TI - Radioimmunoscintigraphy of colorectal carcinoma with a 99Tcm-labelled anti-CEA monoclonal antibody (BW 431/26). AB - Radioimmunoscintigraphy (RIS) with BW 431/26 monoclonal antibody (MoAb) labelled with 99Tcm (962 MBq) has been performed in 64 patients with colorectal carcinoma, one of them with two independent tumours. The group consisted of 46 primary lesions, 15 pelvic recurrences and four suspected recurrences which were shown to be liver metastases. Imaging of liver was obtained in all patients, but surgical liver examination was performed in only 56 of them. Planar scans were obtained at 4 and 24 h postinjection. Tomographic images were also performed in five patients. The final diagnosis was confirmed in all patients by their clinical course and by findings at surgery and pathology. A comparative study between the RIS results and the final diagnosis gave a global sensitivity in primary tumours and pelvic recurrences of 59.7% with an accuracy of 59.0%. When rectal tumours were excluded, the results were 81.1 and 84.9%, respectively. In liver metastases the sensitivity was 50%, with an accuracy of 85.7% and a specificity of 100%. No correlation has been found between CEA serum levels and lesion detection. In conclusion, RIS is a useful technique for the study and localization of colorectal tumours, being also indicated in patients with normal carcinoembryonic antigen (CEA) serum levels and clinical suspicion of illness. PMID- 1589180 TI - Information for patients and staff concerning nuclear medicine. AB - Providing information to patients and staff is an important part of the practice of nuclear medicine. To assist in improving the standard of communications, guidance has been prepared covering the content, style and presentation of letters and leaflets for patients and for medical and nursing staff. Examples are provided which describe nuclear medicine procedures and related radiation safety precautions. They also attempt to answer questions frequently put by the various groups to whom they are addressed. PMID- 1589181 TI - Altered kinetics of 123I-IMP in irradiated rabbit lungs. AB - Radiation-induced alteration of intrapulmonary kinetics of 123I-IMP was investigated in 11 rabbits receiving a 50 Gy dose of radiation to one lung. In all 13 examinations of these rabbits, 3-17 weeks following radiation, the delayed images of 123I-IMP lung scintigrams showed abnormal accumulation in the irradiated lungs. The time-activity curves of the irradiated lung following injection of 123I-IMP had shallower downslopes of both the initial fast phase and the following slow phase than those of the non-irradiated lung. Finally the radioactivity of the irradiated lung exceeded that of the normal lung. The altered intrapulmonary kinetics of 123I-IMP in the irradiated lung was clearly confirmed. 99Tcm-MAA lung perfusion scintigrams showed reduced uptake in the irradiated lungs; the uptake decreased with time following radiation. Pulmonary arterial perfusion was considered to influence the distribution and kinetics of 123I-IMP, however, those of 123I-IMP did not reflect only the pulmonary arterial perfusion observed by 99Tcm-MAA scintigrams. Chest radiography and histological studies revealed a relatively slight change or injury of the irradiated lung in these rabbits. These results indicate that this agent could be useful in detecting and assessing early lung injury induced by radiation, and will give us pathological information in addition to lung perfusion in the peripheral area where the large 99Tcm-MAA molecule cannot reach. PMID- 1589182 TI - Letter from America (1991-92). AIDS. PMID- 1589183 TI - Staging of reflex sympathetic dystrophy with 99Tcm-HSA. PMID- 1589184 TI - Mining deaths decline, but enforcing training might have prevented more. PMID- 1589185 TI - As debate over asbestos risks rages worker health remains central issue. PMID- 1589186 TI - Study of Phillips tragedy gives insights into etiologies of plant blast injuries. PMID- 1589187 TI - Healthcare cost crisis demands trained personnel to initiate proper strategies. PMID- 1589188 TI - Task-specific computer glasses: understanding needs, reaping benefits. PMID- 1589190 TI - Quick response and careful treatment critical for victim of serious burn. PMID- 1589189 TI - New law in the Big Apple mandates CPR infection-control equipment. PMID- 1589191 TI - Intraocular pressure and anterior chamber depth before and after extracapsular cataract extraction with posterior chamber lens implantation. AB - Long-term intraocular pressure (IOP) was evaluated in 41 glaucoma patients after extracapsular cataract extraction (ECCE) with posterior chamber lens (PC-IOL) implantation. All patients were initially monitored for a mean of 19 days. Eight failed to return for reexamination, but follow up of the other 33 continued for a mean of 12 months. IOP dropped significantly and the need for medication was reduced in all patients (particularly in those with open-angle glaucoma and prior iridotomy and iris suturing). The reduction in pressure remained significant in patients with simple or exfoliation glaucoma even after long-term observation. Pressure also significantly dropped in patients who had undergone previous ophthalmic surgery. The pressure drop was possibly due to a surgical deepening of the chamber angle. (Using the laser tomographic scanner, we found the same phenomenon in 50 patients without glaucoma: following ECCE/PC-IOL, the anterior chamber angle widened 9.3 +/- 4.3 degrees.) PMID- 1589192 TI - Clinical experience with the Molteno dual-chamber single-plate implant. AB - A Molteno dual-chamber single-plate implant was placed in 40 consecutive patients, who were followed for a minimum of 6 months. This implant is identical to the single-plate Molteno implant, except for the addition of a pressure ridge to the upper surface of the episcleral plate, which allows the episcleral tissues to function as a temporary, pressure-sensitive valve, limiting the escape of aqueous in the early postoperative period. Confirming earlier studies, we found that use of the modified implant reduced immediate postoperative hypotony, eliminated choroidal hemorrhage, and, by obviating ligature of the silicone tube, permitted immediate reduction of elevated intraocular pressure. PMID- 1589193 TI - Design and results of trabeculectomy operation for use with 5-fluorouracil. AB - We revised our trabeculectomy technique in an effort to minimize the complications associated with the use of 5-fluorouracil (5-FU) in these procedures and then compared the results obtained with this procedure both with (25 patients) and without (25 patients) the use of 5-FU. There was no significant difference between the two groups in terms of mean postoperative IOP at 1 year, number of patients that required needling of the bleb to control postoperative IOP, and number of patients requiring postoperative topical medications to control IOP. Since more (although not significantly more) patients who did not receive 5-FU required needling of the bleb to maintain filtration, and since we were able to achieve satisfactory results in the great majority of cases using only a small total dose of 5-FU, we suggest that it may be simpler to use low doses of 5-FU in all trabeculectomy procedures. PMID- 1589194 TI - Compression sutures and penetrating corneal trauma. AB - A simple technique involving additional compression sutures and the use of a subjective operating keratometer is described for use in managing excessive astigmatism following suturing for penetrating corneal trauma. By minimizing "sutures in" astigmatism following wound closure, this technique can hasten visual rehabilitation. PMID- 1589195 TI - Computed axial tomography on highly myopic eyes following scleral reinforcement surgery. AB - We performed computed tomography (CT) studies on six patients (with follow up ranging from 8 months to 18 years) following scleral reinforcement surgery, comparing the density of the observed implanted scleral material with both normal human sclera and myopic sclera. Results demonstrated the presence of a material on the posterior pole with a density greater than or equal to the experimentally determined density of ungrafted donor sclera. We conclude that CT is a useful method of evaluating both the position and long-term stability of implanted donor sclera. PMID- 1589196 TI - Simultaneous lateral, anterior, and posterior (SLAP) lower-lid blepharoplasty. AB - We report a hybrid of procedures for correcting the aging lower eyelid- transconjunctival blepharoplasty, skin blepharoplasty, and skin-muscle blepharoplasty--that maximizes the strengths of these procedures while minimizing their shortcomings. Our procedure, a simultaneous lateral, anterior, and posterior blepharoplasty, simultaneously attacks the lateral canthal angle, the anterior lamella, and the posterior lamella of the eyelid. PMID- 1589197 TI - Intravitreal antibiotics: accuracy of dilution by pharmacists, ophthalmologists, and ophthalmic assistants, using three protocols. AB - We compared the accuracy with which general ophthalmologists, pharmacy personnel, and ophthalmic assistants diluted intravitreal antibiotics, using a method of their own devising, a new protocol using an insulin syringe, and Duane's protocol. The insulin syringe method proved less accurate and more complex than Duane's protocol, but was better than not using a standardized protocol at all. With all methods, the pharmacy personnel produced the most accurate dilutions, with the least variability. The ophthalmologists' dilutions were much more variable both without a protocol and with the insulin syringe method, but they were acceptable with the Duane's protocol. The ophthalmic assistants produced unacceptable results with all methods. Since the decision to inject antibiotics is usually made under emergency conditions, when errors of dilution are more likely, whenever possible, pharmacy personnel should be entrusted with providing the dosage of medications to be injected intraocularly. If pharmacists are unavailable, ophthalmologists may reconstitute medications using a reliable and simple protocol such as Duane's. PMID- 1589198 TI - Pigmentary dispersion syndrome and pigmentary glaucoma: a new mechanism concept, a new treatment, and a new technique. AB - Reverse pupillary block is introduced as a new cataract-implant complication and as the principle mechanism in pigmentary dispersion syndrome (PDS) and pigmentary glaucoma (PG), causing posterior iris bowing and zonular rubbing. This mechanism was investigated by performing laser iridotomy on six patients. Following surgery, the iris moved forward completely and permanently to the planar position. A new technique, locating the iridotomy by transillumination, reduced the laser energy needed for iridotomy. Laser iridotomy located with transillumination is recommended as the treatment for iris-zonular rubbing in PDS and PG caused by reverse pupillary block. PMID- 1589199 TI - 5-fluorouracil in trabeculectomy for patients under the age of 40 years. AB - In an attempt to enhance the success of trabeculectomy in patients under 40 years old, beginning 48 hours after surgery, we injected 5 to 45 mg (mean, 35 mg) of 5 fluorouracil in 10 eyes of six patients. After a mean follow up of 14.9 months (range, 6 to 27 months), intraocular pressure was below 21 mm Hg in 9 of the 10 eyes, with no antiglaucoma medication. PMID- 1589200 TI - The pigtail probe protected by silicone intubation: a combined approach to canalicular reconstruction. AB - We have devised a method of single-eyelid canalicular reconstruction using the pigtail probe to facilitate identification of the proximal canalicular segment following silicone stent intubation of the normal, uninjured canaliculus. A series of seven acute and two long-standing canalicular lacerations were successfully reconstructed using this technique, which minimizes the risks associated with the use of the pigtail probe. PMID- 1589201 TI - Transconjunctival surgery. AB - Transconjunctival surgery provides excellent exposure of the inferior orbit, leaves no visible scar, and poses less risk of the complications typically associated with transcutaneous techniques. The transconjunctival approach can be combined with lateral canthal techniques to increase exposure and surgical options. We review applications of the transconjunctival approach in blepharoplasty, the repair of orbital floor fractures, socket reconstruction, inferior orbital tumor excision, and orbital decompression. PMID- 1589202 TI - Failure of collagen plugs to predict epiphora after permanent punctal occlusion. AB - In two patients with keratoconjunctivitis sicca, epiphora did not occur after temporary canalicular occlusion with collagen implants, but did occur after subsequent permanent punctal occlusion. This suggests that collagen implants may not always produce total occlusion. Patients should be warned of this possibility. PMID- 1589203 TI - Punctal dyeing: an adjunct to intraoperative lacrimal punctal identification. AB - During lid operations, identifying the lacrimal punctum is sometimes difficult. The difficulty may be increased following local anesthetic infiltration into the medial canthus and manipulation of the lid tissues. Punctal dyeing with a skin marking pen is a simple technique that improves visualization of the lacrimal punctum during surgery in this region. Preceded by punctal dilatation, it lasts for the duration of standard lid or lacrimal procedures. PMID- 1589204 TI - Bilateral congenital posterior-capsular defects: a case report. AB - We report a rare case of bilateral congenital posterior-capsular defects and its successful management by the dry-aspiration technique. To our knowledge, this is the first documented case of a posterior-capsular rupture with no demonstrable cause. PMID- 1589206 TI - Simplified vitreous lavage for bleeding after vitrectomy. PMID- 1589205 TI - The pitfall of dacryostenosis. AB - We examined a 65-year-old woman with complaints of epiphora, which was diagnosed as due to dacryostenosis. After she had undergone dacryocystorhinostomy for this presumed condition, we discovered a large mass protruding through the incision. A biopsy showed anaplastic carcinoma, and a CT scan revealed that the right-side sinuses were filled with tumor. We conclude that the possibility of paranasal sinus tumors should at least be considered before initiating treatment for complaints of epiphora in elderly patients. PMID- 1589207 TI - A paper clip to the rescue. PMID- 1589208 TI - A host-parasite catalogue of the haematozoa of the sub-Saharan birds. AB - The prevalence of avian haematozoa in 826 species of birds representing 73 families of sub-Saharan birds as recorded in the literature or in the files of the International Reference Centre for Avian Haematozoa and the Veterinary Research Institute is presented. The most commonly occurring blood parasites were members of the genus Haemoproteus which were represented by 63 species which occurred in 19.1% of the sample. Twenty-five species of Leucocytozoon were recorded in 8.3% of the birds and represented the second most frequently encountered group of haematozoa. Species of Plasmodium, Trypanosoma, and filarioids (as microfilariae) occurred in 3.5%, 2.5% and 2.8% respectively of the birds sampled; species of Aegyptianella, Atoxoplasma, Babesia and Hepatozoon were infrequently seen. An annotated list of the birds examined for haematozoa is presented and brief descriptions of the species of Haemoproteus and Leucocytozoon in birds of the sub-Saharan zone are included. PMID- 1589209 TI - Effect of intranasal cocaine on the urine drug screen for benzoylecgonine. AB - Otolaryngologists have long recognized the value of cocaine as a topical anesthetic and vasoconstricting agent. It is used in nasal surgery and as a vasoconstrictor before examination. As drug abuse has increased, screening for drugs of abuse has become common. This study was designed to determine how medicinal cocaine affects the urine test for the metabolite benzoylecgonine, the most common screening test for cocaine. Group I consisted of 12 patients scheduled for elective nasal surgery. Cocaine was given in our usual preoperative manner as 4 ml of 4% solution on cottonoids. Group II consisted of 30 volunteers in whom approximately 1 ml of 4% solution was sprayed intranasally. In both groups, a urine sample was collected before dosing and at regular intervals afterwards. All samples were negative before application of cocaine and all were positive 24 hours later. The duration of the positive result had some variability, but all were negative by 72 hours. The results show that medicinally used cocaine does make a drug screen positive. Patients should be informed that cocaine is being used and could cause a positive test for several days. PMID- 1589210 TI - Audiometric comparison of Lassa fever hearing loss and idiopathic sudden hearing loss: evidence for viral cause. AB - A recently published prospective study on acute sensorineural deafness in Lassa fever among a West African population showed the audiometric pattern of a known virally induced hearing loss. Using the audiometric data from the patients with Lassa fever in that study, we analyzed and classified the initial hearing loss and final recovery into three groups by pure-tone average values and then did the same for 222 patients with idiopathic sudden hearing loss (SHL) in our study. Statistical analyses of the severity of initial hearing loss and the hearing recovery pattern indicate that the clinical course of our 222 patients with idiopathic SHL showed no statistically significant differences from the clinical course of the patients with Lassa fever. We found a marked difference in age, however, and a clinically significant difference in the incidence of bilateral hearing loss. In reviewing the literature on sudden sensorineural hearing loss, we found no apparent relation between severity of viral illness and initial hearing loss or subsequent recovery. Cummins et al. suggest that virally induced hearing loss in Lassa fever is linked to the host's immune response and not to the viremia. We thus propose a virally induced immune response mechanism for idiopathic sensorineural SHL. Further prospective studies are needed for verification. PMID- 1589211 TI - Tympanomastoidectomy for chronic otitis media without cholesteatoma. AB - A series of 221 ears with chronic suppurative otitis media without cholesteatoma is presented--84% of the cases were treated using one-stage tympanomastoidectomy and 15% underwent cortical mastoidectomy with planned second-stage tympanoplasty. Mean follow-up period was 6.3 years. Control of infection succeeded in 92% after the primary operation. Failures were most common in ears infected with Pseudomonas aeruginosa. Postoperative cholesteatoma developed in 5 ears (2.2%). Hearing results were unsatisfactory; a postoperative air-bone gap within 20 dB was achieved in only 62%. In revision operations, retained mastoid air cells were found in 64% of ears with recurrent or persistent discharge. Thirty-seven percent of patients with unsuccessful outcome were observed to have a possible underlying or concomitant disease. The importance of intensive preoperative conservative treatment and careful surgical technique is stressed. PMID- 1589212 TI - An anatomic study of the external laryngeal framework with surgical implications. AB - Precise knowledge of the level of the vocal fold as projected on the external thyroid cartilage is of critical importance for the performance of thyroplasty type I and supraglottic laryngectomy. Measurements of the external laryngeal framework were made on the larynges of 18 human cadavers in order to identify landmarks that will aid the surgeon in determining endolaryngeal anatomy. On the basis of our results, the following guidelines are recommended: (1) Thyroid cartilage incision for supraglottic laryngectomy should be made on a line joining the juncture of the upper one third and lower two thirds of the midline length and the juncture of the upper one third and lower two thirds of the oblique line. This will ensure a position above the level of the anterior commissure and the true vocal cord; (2) In thyroplasty type I, the superior border of the thyroid cartilage window should be made at a line joining the midpoint of the midline length and the juncture of the upper two thirds and lower one third of the oblique line. Formation of the cartilage window according to this guideline will ensure its placement lateral to the vocalis muscle. PMID- 1589213 TI - Tympanostomy tube insertion: anterosuperior vs. anteroinferior quadrant. AB - We studied the extrusion rate of Paparella type I tympanostomy tubes in the anterosuperior quadrant compared to those placed in the anteroinferior quadrant in a prospective study. Thirty-five patients were evaluated. The duration (mean +/- SEM) in the anteroinferior quadrant was 211 +/- 18 days, whereas the duration in the anterosuperior quadrant was 211 +/- 11 days. We conclude that placement in the anterosuperior quadrant does not prolong duration of these tympanostomy tubes. PMID- 1589214 TI - Antibiotics and topical surgical preparation solution in septal surgery. AB - One thousand forty patients undergoing septal surgery of the nose were included in this 5-year study of no prophylactic antibiotics and no topical surgical preparation solution before surgery. Minor nasal infections developed in only five patients (0.48%) postoperatively. All five of these patients responded to oral antibiotic therapy and did not require hospitalization or intravenous antibiotic treatment. The incidence of infectious complications resulting from nasal surgery without the use of topical surgical preparation solution and without prophylactic antibiotics is minimal. No topical surgical preparation solution and no prophylactic antibiotic technique is a safe and acceptable approach for septoplasty and rhinoplasty surgery. PMID- 1589215 TI - Repair of mandibular fractures: plating vs. traditional techniques. AB - The treatment of mandibular fractures is a challenge for the otorhinolaryngologist-head and neck surgeon. Recent technologic advances have resulted in the development of rigid fixation techniques that hold promise for the early and optimal restoration of mandibular structure and function. The purpose of this article is to review the dental and orthopedic principles used in our mandibular fracture management, describe compression plating methodology, and discuss optimal techniques for its use. Results using rigid fixation procedures were compared with those using a variety of more traditional techniques in a retrospective analysis of 57 cases. The advantages, limitations, and indications for use of plating technology are discussed, and prevention of complications is emphasized. PMID- 1589216 TI - Significance of borderline levels of specific IgE obtained by FAST-Plus assay. AB - The significance of "borderline" levels of allergen-specific IgE as measured by in vitro assays has been questioned. Patients whose specific IgE tests Patients were tested for twelve antigens using the FAST-Plus methodology. All 0/1 results were checked using skin tests at a 1:500 concentration. Positive (histamine) and negative (diluent) controls were used. The antigen-induced wheals were compared with those produced by a control wheal of 2% glycerine (the glycerine concentration in a 1:500 dilution). Positive wheals were arbitrarily considered to be those whose diameter after 10 minutes exceeded that of the glycerine control wheal by 2 mm or more. Using the limits of calibrator fluorescence for the FAST-Plus test in effect before 1990, a significant discordance between skin test results and the class 0/1 in vitro readings was evident. Using the standards in effect since 1990, marked concordance between class 0/1 results and positive skin tests was noted. This was most marked for pollens, less so for molds. Using current standards, FAST-Plus class 0/1 results are best considered positive (pending clinical confirmation), rather than negative. PMID- 1589217 TI - Barium swallow is a predictor of salivary fistula following laryngectomy. AB - Pharyngocutaneous salivary fistula after laryngectomy is a serious complication that can lead to prolonged hospitalization and increased patient morbidity. A postoperative barium swallow provides the surgeon with information regarding the integrity of the pharyngeal suture line. In an attempt to determine whether this information can be used to predict or prevent salivary fistula, we reviewed the records of 109 patients who underwent total laryngectomy, including 51 who had a barium swallow before they began oral intake. Ten patients (20%) demonstrated a sinus tract originating from the pharyngeal suture line. A clinical salivary fistula developed in all four patients with a sinus tract 2 cm or longer, but in only one of six patients with a tract shorter than 2 cm. Other factors predictive of salivary fistula included tumor stage, previous radiation therapy, and the presence of concurrent postoperative complications. A single fistula developed in the 58 patients not studied with barium. Information provided by postlaryngectomy barium swallow appeared to predict, but not prevent salivary fistula formation. PMID- 1589219 TI - Tracheomalacia repair using ceramic rings. AB - Tracheomalacia resulting from tracheostomy or compressive thyroid disease often represents a difficult problem in airway management. In an attempt to improve this condition, biocompatible ceramic rings were surgically implanted in 16 patients to restore normal patency of the airway by first expanding the tracheal lumen lateral, and then in an anterior dimension. Preoperatively, patients displayed moderate to severe obstruction with marked restrictions in lifestyle, as confirmed by history, physical examination, and airway resistance studies. Additionally, three of these patients were trach-dependent at the time of implantation. Postoperatively all 16 patients have normal airway resistance parameters with a dramatic improvement in lifestyle, whereas the three with tracheostomy were successfully decannulated. The routine use of these rings has alleviated the need for rib/cartilage grafts, primary resections with anastomosis, prolonged periods of cannulation, and multiple surgeries. Our experience in the use of ceramic rings for tracheomalacia repair will be presented, highlighting selection criteria for their use, intraoperative placement, perioperative complications, and post-operative followup for a minimum of 6 months. PMID- 1589218 TI - Head and neck lymphoma in patients with the acquired immune deficiency syndrome. AB - A marked increase has recently been noted in the incidence of lymphoma in patients with AIDS. These lymphomas are generally high-grade, of B-cell origin, and often involve extranodal sites. Reported here are twenty patients with AIDS in whom symptoms and physical findings developed related to the head and neck region as a result of lymphoma. The tumor was observed in a variety of sites, including the nasopharynx, orbit, submandibular triangle, anterior and posterior cervical triangles, supraclavicular fossa, and the hypopharynx. Sixteen tumors were large cell nonHodgkin's B-cell lymphomas, three were small cell nonHodgkin's B-cell lymphomas, and one was Hodgkin's disease, mixed cellularity. All were treated with combination chemotherapy. A high degree of suspicion for lymphoma is required in treating any patient with AIDS who has a rapidly enlarging mass in the head and neck. If needle aspiration is nondiagnostic, excisional biopsy should be performed after a complete head and neck evaluation. Although the development of lymphoma associated with AIDS portends a grave prognosis, prompt diagnosis will allow an improved chance of remission of the lymphoma. PMID- 1589220 TI - Squamous cell carcinoma in older patients without risk factors. AB - Ten patients over sixty years of age with no history of tobacco or alcohol use were treated for squamous cell carcinoma of the upper aerodigestive tract between 1979 and 1991. Nine of these ten patients were women with lesions confined to the oral cavity and oropharynx. Modes of treatment included surgery, radiation, or a combination of surgery and radiation. Followup from 1 to 10 years revealed two deaths from local and distant spread, and eight patients with no evidence of disease. Recurrences after treatment were aggressive and occurred within the same region as the primary lesion. Although most patients with upper aerodigestive squamous cell carcinoma are men with alcohol and/or tobacco exposure, this study demonstrates findings consistent with field cancerization in a group of older women with no risk factors. PMID- 1589221 TI - Congenital anomalies limited to the middle ear. AB - Congenital anomalies of the middle ear are occasionally encountered during surgery for conductive hearing loss and are unexpected in patients with no other deformities. We reviewed 12 such patients operated on at The New York Eye and Ear Infirmary from 1985 through 1989. Nine of the patients (75%) had unilateral conductive hearing loss whereas three (25%) had bilateral symptoms. One had bilateral congenital middle ear anomalies. Three patients (25%) had anomalies limited to the malleus and scutum. Five patients (47%) had agenesis of the oval window. After reconstructive surgery, 72% of patients had hearing improvement ranging from 13 to 38 dB. The etiology of these anomalies is discussed and their evaluation and surgical indications are presented. PMID- 1589222 TI - Bipolaris-caused fungal sinusitis. PMID- 1589223 TI - Facilitating voice recording under consistent conditions in the clinical setting. PMID- 1589224 TI - Endaural encephalocele. PMID- 1589225 TI - From the National Institute on Deafness and Other Communication Disorders. PMID- 1589226 TI - Acoustic neuroma: cost-effective approach. PMID- 1589227 TI - First-line management of sinusitis. PMID- 1589228 TI - Nasal button battery. PMID- 1589229 TI - Unexpected finding of a stapes prosthesis. PMID- 1589230 TI - Exercise-induced analgesia: fact or artifact? AB - This study critically examines the reported exercise-induced analgesia effect in view of the potential stress-induced analgesia of pain testing itself. Two designs were used to test whether previous findings of analgesia were induced by the exercise procedures or by the stress of the pain testing procedures themselves used in such experiments. In the first design, post-test cold pressor pain ratings were obtained from college students following exercise (bicycle ergometry) and two control tasks (minimal exercise and non-exercise). No significant differences between these groups were found. In the second design, exercise and non-exercise groups pre-exposed to cold pressor pain testing were compared to groups that were not pre-exposed to pain testing. There were no significant effects for exercise; however, significant analgesia effects for pain test pre-exposure were demonstrated. Therefore previous research claiming exercise-induced analgesia may have confounded the effects of exercise with the effects of pre-exposure to pain testing itself. PMID- 1589231 TI - Strengthened estimates of individual pain trends in children following bone marrow transplantation. AB - Pre-transplant conditioning regimens for bone marrow transplantation often cause oral mucositis and severe pain. We evaluated the agreement of self- and parent reports of daily oral mucositis pain in children between the ages of 6 and 16 years. Child patients were asked to report their pain on visual analog scales (VAS) daily for 20 days following their transplants. Daily VAS ratings were also obtained from one of the parents. The analysis sample consisted of ten children aged 7-9, nine children aged 10-12, eight children aged 13-16, and their parents. We modeled individual child and parent reports as quadratic functions of the number of days post transplant. Empirical Bayes/restricted maximum-likelihood estimates were obtained of individual coefficients, treated as random effects, and age group coefficients, treated as fixed effects. Parents exhibited higher average pain curves than their children in each of the three age groups. The middle age group reported the highest average pain. Average within-person error variances representing unreliability were 692.2, 461.9, and 303.9 for young, middle, and old children, respectively; for parents, the corresponding error variances were 375.1, 413.3, and 252.4. These results challenge the presumption that children tend to over-report pain but are consistent with the contention that younger children may be less reliable reporters than adolescents and adults. PMID- 1589232 TI - A double-blind trial of naloxone in central post-stroke pain. AB - Intravenous naloxone has been claimed to produce pain relief in opioid-resistant central post-stroke pain (CPSP, 'thalamic syndrome'). In a double-blind trial, carried out in 20 patients with established CPSP, naloxone (up to 8 mg in 20 ml vehicle) was tested against normal saline; each patient was randomly given naloxone or saline and the other substance 2 or 3 weeks later. VAS and verbal pain scores were obtained immediately before and after naloxone or saline injection, and subjective ratings followed for 2 weeks. Three patients obtained transient pain relief with naloxone, 4 with saline, and another 4 with both. Statistical tests failed to show any influence of giving naloxone first or second. In all cases except one, pain relief had disappeared by the evening of the day on which the test was performed; one case, following naloxone, continued to experience pain relief until the following morning. We therefore conclude that intravenous naloxone is of no value in alleviating the pain of CPSP. PMID- 1589233 TI - Neuropsychological effects of methylphenidate in patients receiving a continuous infusion of narcotics for cancer pain. AB - Twenty consecutive patients with cancer pain receiving a continuous subcutaneous infusion of narcotics were admitted to a double-blind, crossover trial designed to assess the effects of methylphenidate on neuropsychological functions. After a baseline assessment, patients were randomized to receive methylphenidate orally at 08.00 h for 2 consecutive days or placebo. During day 3, a crossover took place and patients received the alternate treatment for 2 more days. At the end of the trial, both patients and investigators were asked to choose blindly the most effective treatment. Cognitive tests (finger tapping, FT 10 and 30 sec; arithmetics, A; reverse memory of digits, RM; and visual memory, VM) were performed in all patients before and 45 min after their morning dose of narcotics for 2 consecutive days. Mean percentual change in FT 10 sec, FT 30 sec, A, RM, and VM after the narcotic dose were 89 +/- 12%, 98 +/- 15%, 108 +/- 17%, 101 +/- 17%, and 97 +/- 21% in the placebo group versus 119 +/- 16 (P less than 0.001), 130 +/- 19 (P less than 0.001), 78 +/- 21 (P less than 0.001), 125 +/- 28 (P less than 0.01), and 128 +/- 26 (P less than 0.001) in the methylphenidate group, respectively. After completion of the trial, methylphenidate was chosen blindly by the patient and investigator in 13 and 14 cases, placebo in 3 and 2 cases, a "no choice" in 3 and 3 cases, respectively (P less than 0.01). Our results suggest that methylphenidate is capable of improving cognitive function in patients receiving high doses of opiates subcutaneously. More research is necessary in order to determine the duration of cognitive improvement after each dose of methylphenidate as well as the best type and dose of amphetamine. PMID- 1589234 TI - The effect of adding calcitonin to physical treatment on reflex sympathetic dystrophy. AB - The efficacy of intranasal salmon calcitonin was examined in a double-blind randomized study in reflex sympathetic dystrophy. Sixty-six patients were randomly divided in two groups receiving physiotherapy. In addition group I also received 3 x 100 U/day of salmon calcitonin by intranasal spray whereas group II received 3 sprays of placebo. The pain and the range of motion were improved by calcitonin administration. Similarly the patients' ability to work was also improved. The results confirmed that salmon calcitonin has an effect but that this effect was not equally observed on all parameters analyzed. It was most marked on pain (at rest and on movement) and on the ability to work. PMID- 1589235 TI - Responsiveness to laboratory pain in women as a function of age and childbirth pain experience. AB - Pain responsiveness was investigated experimentally as a function of age and childbirth pain experience. Sensitivity to cold pressor-induced pain was assessed through threshold, tolerance, and visual analog pain ratings. It was hypothesized that childbirth pain experience would mostly modify experimental pain judgment, in accordance with the adaptation-levels model. That is, childbirth pain would be used as an "anchor" in evaluating other painful events. Fifteen parous women were compared to 12 nulliparous women of the same age (mean age: 35 years) as well as to 15 nulliparous younger women (mean age: 24 years). This comparison was undertaken in order to distinguish the effects of age, which was found to correlate with pain threshold. Analysis of variance comparing the three groups of women was performed on each of the three cold pressor measures. A significant effect was found for pain threshold. Multiple comparisons indicated that parous women had a higher pain threshold than both groups of nulliparous women which did not differ from one another. Thus, painful childbirth experience is sufficient to raise cold pressor pain threshold. This finding has never before been reported in the pain literature. It is consistent with anecdotal reports from parous women who, when providing cold pressor pain judgments, say that "nothing compares to labor pain." PMID- 1589236 TI - The need for pain relief in uncomplicated deliveries in an alternative birth center compared to an obstetric delivery ward. AB - The need for pain relief during uncomplicated labour and delivery was studied in 125 women attending an Alternative Birth Center (ABC) and 170 women attending an obstetrical ward. The ABC was staffed only with midwives and assistant nurses who took care of all deliveries. In case of complications the doctor on duty at the obstetrical ward could come in a few minutes and the patient was transferred to the obstetrical ward. At the ABC the delivery room was next to the sleeping rooms and the living room and the woman in labour could have a chat with the women, who had given birth. At the obstetrical ward this was not possible. The delivery rooms were on one floor, and after giving birth the woman was moved to another floor. Women at the ABC were older and had a higher social status than women at the obstetrical ward. Twenty four of the 170 women had initially planned to give birth at the ABC but gave birth at the obstetrical ward due to accommodation restrictions at the ABC. Women refused by the ABC resembled women giving birth at the ABC but their need for pain relief was identical with the other women giving birth at the obstetrical ward. Pain relief with pethidine was 4 times more frequent among women giving birth at the obstetrical ward (18%) than at the ABC (4.8%). Pethidine was predominantly administered to young women and primiparas at the obstetrical ward and to women with prolonged labour at both birthplaces. PMID- 1589237 TI - Acetylsalicylic acid activates antinociceptive brain-stem reflex activity in headache patients and in healthy subjects. AB - The exteroceptive suppression (ES) of electrical activity in the temporal muscle is an inhibitory antinociceptive brain-stem reflex. We investigated whether aspirin can significantly modulate latencies or durations of the early (ES1) and late (ES2) exteroceptive suppression periods of electrical activity in the temporal muscle. Participating in the randomized double-blind crossover study were 20 patients with migraine without aura, 20 patients with tension-type headache, and 20 healthy subjects. ES1 and ES2 elicited by an electrical stimulus of 20 mA lasting 0.2 msec were recorded during maximal voluntary contraction of the mastication muscles before and 30 min after medication. In a randomized and double-blind fashion half of the subjects were given 1200 mg of aspirin in the form of an effervescent solution and the other half were given an identically tasting solution without aspirin. One week later the experiment was repeated with the substances exchanged in crossover fashion. The administration of placebo as well as aspirin caused a highly significant increase in ES1 duration (P less than or equal to 0.001). While aspirin caused a highly significant increase in ES2 duration (P less than or equal to 0.001) the taking of placebo showed no significant effect on ES2 duration. In giving aspirin as opposed to the placebo, there was a significant interaction between groups and drug effect on the latency of ES1; whereas in migraine patients and in patients with tension-type headache the latency of ES1 was reduced by administration of aspirin, it was increased in healthy subjects (P less than or equal to 0.05). Neither aspirin nor placebo significantly varied the ES2 latency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589238 TI - Cephalic muscle tenderness and pressure pain threshold in a general population. AB - Tenderness and pain thresholds in pericranial muscles were studied in a general population. A random sample of 1000 adults aged 25-64 years was drawn as part of the Glostrup Population Studies, and 740 adults were examined. This study was part of a multifacetted, epidemiological study of different headache disorders according to the new headache classification. Manual palpation and pressure pain threshold with an electronic pressure algometer were performed by observers blinded to other information such as the person's history of headache, previous illness and mental state. The muscles most commonly tender to manual palpation were the lateral pterygoid (55%), the trapezius (52%), and the sternocleido mastoid muscles (51%). Females were more tender than men in all the muscles examined by manual palpation. In total, the young age group was more tender than the old age group (P = 0.03). Pressure pain thresholds on temporal muscles showed lower thresholds in women than in men (P less than 10(-3)), and in the total population thresholds increased with age (P less than 0.05). No side-to-side difference in tenderness by manual palpation was found, while the right side showed increased pain thresholds in right-handed individuals (P less than 10( 4)). No side-to-side difference was found in left-handed persons. This study provides data about the normal population and forms the necessary basis for evaluating the importance of muscle tenderness in headache subjects and other selected groups. PMID- 1589239 TI - An evaluation of the sensitivity and specificity of medical thermography for the documentation of myofascial trigger points. AB - This investigation evaluated the diagnostic value of medical thermology for the documentation of myofascial trigger points. Previous investigators have suggested that circumscribed 'hot spots' reflect the thermal activity of trigger points. A total of 365 patients participated in the four separate experiments. Upper back trigger points were isolated via palpation. A separate thermographic examination, specific to that experiment, was conducted by a technologist who was blind to the presence or absence of trigger points. The first experiment examined the Swerdlow Dieter protocol. Fifty percent of the subjects with trigger points demonstrated hot spots. Over 60% of patients without trigger points exhibited hot spots. Chi square analysis determined that there was no significant difference between these two groups. The majority of hot spots were unrelated to trigger point location. The second experiment evaluated the protocol suggested by Fisher. Hot spots were evident in the majority of subjects, regardless of whether they possessed trigger points. The third experiment investigated hot spot persistence by adapting the Weinstein-Weinstein alcohol spray protocol. Chi-square analysis found no significant difference between the effect which spray had on the hot spots of patients with or without trigger points. Following a post-spray machine adjustment, the majority of pre-spray hot spots could be reproduced. The final experiment used a pressure threshold meter (PTM) to evaluate the number of kilograms pressure a patient's hot spot could comfortably sustain in comparison to the opposite location on the back. Using the t test, no significant difference was found between the kilograms pressure withstood by hot spot and non-hot spot regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589240 TI - Responses of motor units during the hind limb flexion withdrawal reflex evoked by noxious skin heating: phasic and prolonged suppression by midbrain stimulation and comparison with simultaneously recorded dorsal horn units. AB - In rats anesthetized with sodium pentobarbital, we quantitatively analyzed descending modulation from the midbrain of a nociceptive flexion withdrawal reflex and responses of associated spinal neurons. We monitored the isometric force of hind limb withdrawal elicited by noxious heat stimuli (42-54 degrees C, 10 sec) on the hind paw. In one series of experiments, single-fiber EMG electrodes recorded responses of single muscle fibers (i.e., motor units) in biceps femoris during the hind limb withdrawal, without and during electrical stimulation in the midbrain periaqueductal gray (PAG) or lateral midbrain reticular formation (LRF). In a second series, responses of single lumbar dorsal horn neurons were also recorded simultaneously. Withdrawal force and associated motor unit responses were suppressed for prolonged periods (4 to greater than 60 min) following the initial episode of PAG or LRF stimulation in 40% of the rats, while they were suppressed phasically (i.e., only during brain stimulation) in the remainder. Motor unit responses increased in a graded fashion with increasing skin stimulus temperature from threshold (45 degrees C) to 54 degrees C. During PAG stimulation, the slope of the rate coding function was reduced with no change in threshold temperature. During LRF stimulation the rate coding function was shifted toward higher temperatures with increased threshold (47 degrees C). In 14 experiments 43 paired recordings were made from a dorsal horn and a motor unit during hind limb withdrawals. Mean latency to onset and peak of the heat-evoked response was shorter for dorsal horn compared to motor units. In 6/14 rats withdrawal force and motor unit responses were significantly suppressed for more than 8 min following mechanical placement of the stimulating electrodes and/or the initial episode of midbrain stimulation, while the simultaneously recorded dorsal horn unit responses remained constant. Following supplemental administration of pentobarbital (10-30 mg/kg i.v.), withdrawals and motor unit responses to heat were suppressed while dorsal horn unit responses were unchanged or enhanced. Also, in 12/42 cases, withdrawals and motor unit responses decremented markedly during the initial 3 trials of heat, while simultaneously recorded dorsal horn unit responses remained stable. These results indicate that the withdrawal reflex and associated motor units can be markedly suppressed in the absence of concomitant changes in responsiveness of dorsal horn neurons, and are discussed in terms of the neurocircuitry of spinal flexor reflexes and their descending modulation. PMID- 1589241 TI - Quantitative sensory tests in patients with neuralgia 11 to 25 years after injury. AB - In a previous study quantitative sensory tests were used to characterize the symptoms in patients with post-traumatic neuralgia in the hand. Two types of pain syndromes were identified, sympathetically maintained pain (SMP), and sympathetically independent pain (SIP). These two syndromes had different sensory profiles with regard to temperature discrimination and cold and heat pain thresholds. The aim of the present study was to investigate the development of symptoms 10 years later. Eighteen previously investigated patients were contacted and all answered questions concerning their symptoms. Of these, two SIP and eight SMP patients agreed to undergo quantitative sensory testing. The outcome of these tests and the patients' own reports indicated that patients with SMP, who were not repeatedly treated with sympathetic blocks, did not show any remarkable spontaneous improvement of symptoms over a decade. The SMP patients still exhibited their characteristic sensory profile with moderate impairment of temperature discrimination and allodynia to cold, heat and vibratory stimuli. However, some changes with time were observed with respect to warm-cold difference limen and vibration allodynia. Comparison with data obtained from an age-matched group of healthy individuals indicated that these changes were due to age-related factors. PMID- 1589242 TI - Management of intractable back pain from caudal ependymoma with spinal methylprednisolone, bupivacaine and morphine. PMID- 1589243 TI - Morphine-3-glucuronide may functionally antagonize morphine-6-glucuronide induced antinociception and ventilatory depression in the rat. AB - The effects of the major morphine metabolites, morphine-3-glucuronide and morphine-6-glucuronide, on nociception were assessed by the tail-flick, hot-plate and writhing tests in the rat. Morphine-3-glucuronide (M3G) 1.1 x 10(-9) mol (0.5 micrograms) or saline was injected intracerebroventricularly (i.c.v.) or intrathecally (i.t.) followed by a second injection of 2.0 x 10(-10) mol (0.1 microgram) or 2.0 x 10(-11) mol (0.01 microgram) morphine-6-glucuronide (M6G) 10 min later. Administration of M3G (i.c.v.) significantly attenuated the antinociceptive effects of M6G in the hot-plate test. After i.t. administration, the antinociceptive effect of M6G in all three tests was significantly reduced in the M3G pretreated group compared to the group receiving saline. The ventilatory effects of 4.0 x 10(-9)-1.0 x 10(-8) mol (2-5 micrograms) M6G and 1.7-2.2 x 10( 8) mol (8-10 micrograms) M3G given i.c.v. were studied by a whole-body plethysmographic technique in halothane anaesthetized rats. Separate groups of rats received M3G followed by M6G injection or vice versa. In animals receiving M3G there was a prevention or attenuation of the M6G induced depression of respiratory frequency, tidal volume and minute ventilation compared to control groups receiving M6G in combination with saline. These results show that M3G may functionally antagonize the central antinociceptive effects as well as the ventilatory depression induced by M6G. Interestingly, M3G was more potent in antagonizing the M6G-induced analgesia after i.t. administration than that after i.c.v. administration, which may suggest that the spinal cord is more sensitive to the non-opioid excitatory effects of M3G than supraspinal structures. PMID- 1589244 TI - The effects of streptomycin on autotomy. AB - Thirty-six rats with sciatic nerve transections and autotomy scores 1-2 were divided into 3 groups. Two groups were re-operated and injected with streptomycin sulphate or saline into the polyethylene tube around the neuroma. In the third group, streptomycin was injected at the sciatic nerve, extraneurally, proximal to the tube. Streptomycin injected into the polyethylene tube suppressed autotomy scores during the entire postinjection period. At the eighth postinjection week, none of the rats from this group reached the maximal autotomy score. PMID- 1589245 TI - Systemic lidocaine silences ectopic neuroma and DRG discharge without blocking nerve conduction. AB - Systemic application of lidocaine in rats suppressed ectopic impulse discharge generated both at sites of experimental nerve injury and in axotomized dorsal root ganglion (DRG) cells. ED50 for DRGs was significantly lower than for the injury site. Lidocaine doses effective at blocking ectopic discharge failed to block the initiation or propagation of impulses by electrical stimulation, and only minimally affected normal sensory receptors. This selectivity may account for the effectiveness of systemic local anesthetics and other drugs that share the same mechanism of action (notably certain anticonvulsants and antiarrhythmics), in the management of neuropathic paresthesias and pain. In addition, it may account for the prolonged analgesia sometimes obtained using regional local anesthetic block. PMID- 1589246 TI - Nalbuphine does not act analgetically in electrical painful tooth pulp stimulation in man. AB - Nalbuphine is a mixed opioid agonist/antagonist, the analgesic properties of which are still open to debate. In a randomized and placebo-controlled protocol, we compared its effects (0.2 mg/kg) on man's perception of multimodal stimuli (i.e., nociceptive, acoustic and visual) to those of aspirin (acetylsalicylic acid, 10 mg/kg) and meperidine (0.5 mg/kg). Amplitudes and latencies of the evoked potentials (EP), tolerance maxima to painful tooth pulp stimuli, and subjective intensity ratings were measured as indicators of drug induced perception differences. After nalbuphine, the EP amplitudes markedly decreased while the stimuli of each modality were rated by the subjects to be of higher intensity. Also, the tolerance maxima of painful tooth pulp stimulation were reduced by nalbuphine, and naloxone did not have additional effects. In contrast, after aspirin and meperidine, the subjective pain ratings corresponded to the reduction of nociceptive EP amplitudes. Tolerance maxima to painful stimulation were also increased by both drugs. While aspirin did not influence acoustic and visual perception, meperidine caused a slight increase in EP amplitudes as well as in the intensity ratings of these stimuli relative to placebo. Thus, at the dose studied, nalbuphine did not act analgetically. The amplitude reduction of nociceptive EP suggested that nalbuphine had analgetic properties. These were, however, not confirmed by subjective pain ratings nor by changes in tolerance maxima. PMID- 1589247 TI - Intracerebroventricular salmon calcitonin reduces autotomy behavior in rats after dorsal rhizotomy. AB - We studied the effects of intracerebroventricularly (ICV) administered salmon calcitonin (sCT) on the self-mutilation behavior (autotomy) of rats after dorsal rhizotomy. sCT was given 2 micrograms/rat ICV, on alternate days) from day 15 to day 40 after surgery and autotomy was scored until day 60. Autotomy scores were significantly reduced during treatment but once the ICV sCT was stopped mean values for the treated group gradually returned to control levels. These data support the concept that autotomy is a useful model of chronic pain, sensitive to centrally acting antinociceptive agents. In addition, these findings extend the knowledge of the antinociceptive profile of sCT and are in agreement with recent clinical observations. PMID- 1589248 TI - Chronic pain-related syndrome in rats after ischemic spinal cord lesion: a possible animal model for pain in patients with spinal cord injury. AB - We examined a pain-related syndrome, which includes mechanical allodynia and autotomy, in rats after ischemic spinal cord injury photochemically induced by laser irradiation for 5-20 min. This procedure results in an acute allodynia-like phenomenon which lasts for several days and is possibly related to dysfunction of the GABAB system in the spinal cord. In some animals this is followed by a chronic allodynia-like symptom with an onset varying between 1 week and 1.5 months after injury, expressed as a clearly painful reaction to light pressure applied to a skin area at or near the dermatome of the injured spinal segments. In the majority of rats the allodynia persists over several months, in some cases accompanied by autotomy of the hind paws. Pharmacological studies indicated that the allodynia in the majority of rats could be relieved by systemic tocainide (75 mg/kg). Morphine was only effective at a sedative dose (5 mg/kg). The allodynia was not relieved by baclofen, muscimol, clonidine or carbamazepine. Low-dose systemic pentobarbital (5 mg/kg) had a slight beneficial effect. Guanethidine (20 mg/kg, s.c.) did not abolish the allodynia in most of the rats. Histological examination revealed massive damage in the spinal cord. The dorsal roots of the irradiated segments were also injured. No morphological abnormalities were seen in the dorsal root ganglia. The mechanism that may account for this chronic pain related syndrome in spinally injured rats probably involves abnormalities in the central nervous system. The allodynia seen in chronic spinally injured rats was similar to some painful symptoms in patients after spinal cord injury or stroke. It is suggested that the chronic allodynia-like phenomenon may represent an animal model for studying the mechanisms of chronic central pain. PMID- 1589249 TI - Comments on L. Jacobsen et al., Pain, 45 (1991) 105-106. PMID- 1589250 TI - Comments on I.M.C. Clarke in Pain, 45 (1991) 167-170. PMID- 1589251 TI - Colour duplex scanning and phlebography in deep vein thrombosis. AB - Clinical evaluation of deep venous thrombosis is often unreliable. Recently it has been shown that deep venous thrombosis may be detected with colour duplex scanning which is safer than phlebography. However it is not clear how colour duplex correlates with phlebography. One hundred and twenty consecutive patients with suspected deep vein thrombosis were studied by colour duplex scanning and phlebography to compare the two methods. Both tests were positive in 102 limbs and negative in 16 limbs. In two cases of below-knee thrombosis colour duplex was negative while phlebography showed small localised thrombosis. The sensitivity of colour duplex was 98%, its specificity and positive predictive value 100% and its negative predictive value 88.8%. In conclusion colour duplex appears to be as effective as phlebography in detecting deep venous thrombosis above knee. PMID- 1589252 TI - Helicobacter pylori infection: comparison among four different therapeutic regimens. AB - Helicobacter pylori is both virulent and pathogenic, yet it is not clear what is the best way to treat the infection. This study compares the ability of 4 regimens of colloidal bismuth subcitrate (CBS) 120 mg q.i.d. for 4 weeks, combined with one or two antibiotics, to eradicate helicobacter pylori and assesses the outcome of eradication on antral gastritis and on symptoms of non ulcer dyspepsia in 140 consecutive subjects (44 duodenal ulcers and 96 non ulcer dyspepsia). Endoscopy with antral biopsies was repeated in all patients before (T0) and one month after stopping treatments (T2) while duodenal ulcers were endoscoped also at the completion of treatments (T1). The four regimens showed similar eradication and ulcer healing rates (p = ns). After treatments (T1), about 60% of dyspeptic patients achieved a subjective improvement, not significant despite therapeutic regimen, and persisting at T2. Antral gastritis significantly improved after treatments (p less than 0.0001), even with the persistence of the infection (p less than 0.001). The 4 regimens are relatively safe, as no abnormality in laboratory assessment was found, albeit the frequency of side effects (most of whom tinidazole related) and the difficulty of the schedules (6-10 tablets/day) may limit patient compliance. PMID- 1589253 TI - Failure in intrauterine contraception. Analysis of 137 cases of unfavourable outcome. AB - 137 cases of unfavourable outcome in IUD insertion (i.e. early removal or expulsion because of complications) were investigated as regards age, parity, previous intrauterine contraception, previous induced abortion, type of device inserted, and type of complications observed. Moreover, this group was compared for each feature mentioned with a control group of 454 women who successfully concluded the prescribed period from the insertion. All the devices were inserted with a significantly higher rate of favourable outcome in pluriparous versus nulliparous patients; age probably didn't affect the outcome, but strongly conditioned the prevalence of particular complications such as PID and abnormal bleeding. Progesterone-loaded IUD didn't show a more favourable outcome than copper devices. PMID- 1589254 TI - Pulmonary function and morbidity in textile mill workers. AB - The study was conducted in a large cotton textile mill in Surat City. A selected number of 278 employees were evaluated for social, anthropological and pulmonary functions. No parameters except the period of exposure to dust reduced pulmonary function; it was statistically significant in the case of vital capacity and maximum breathing capacity. Out of 23.94% pulmonary morbidity observed, the byssinosis rate was 1.62. PMID- 1589256 TI - Efficacy and acceptability of transdermal estradiol in the treatment of postmenopausal bone loss. AB - In order to assess the effects and acceptability of transdermal estradiol on the prevention of the loss of bone mass, the Authors administered transdermal estradiol (ETTS 50 mcgr/day) for 3 weeks and, cyclically, medroxyprogesterone 10/mg/day from day 10 to day 21 of each cycle for 12 months, to 20 operated patients for bilateral ovariectomy. Primary markers of the bone turnover (hydroxyproline urinary, osteocalcin, PTH) were estimated before therapy and after 3, 6, 9, 12 months. The BMD was evaluated before therapy and after 6 and 12 months. Our study clearly shows that the transdermal administration of estradiol prevents the postmenopausal bone loss, also in postmenopausal women at higher risk of developing osteoporosis as those evaluated in our study. PMID- 1589255 TI - Serum lipase assay. A test of choice in acute pancreatitis. AB - We evaluated the clinical accuracy of an automated turbidimetric assay for serum lipase determination in order to screen for acute pancreatic damage. Seventy patients with pancreatic and thirty with nonpancreatic digestive diseases were studied. Fifty-two healthy subjects were also studied as controls. Serum lipase concentrations were abnormally high in all patients with acute pancreatitis and in 3 (10%) in the group of 30 patients with nonpancreatic acute abdomen. In the 35 patients with chronic pancreatitis studied during clinical remission, serum lipase levels were abnormally high in 8 (23%), and abnormally low in 3 (9%). In the 9 patients with pancreatic cancer, 4 (44%) had abnormally elevated serum lipase values and 1 (11%) abnormally low. The results indicate that serum lipase determination is useful in the emergency diagnosis of acute pancreatic damage because of its high sensitivity and specificity. In patients with chronic pancreatitis and in patients with pancreatic carcinoma serum lipase determination is of limited value. PMID- 1589257 TI - Familial varicocele. AB - Described are two families in each of which two young males had varicocele. HLA A, B, C and D5R antigen studies were performed in one family but no genetic factors could be determined. In a review of several large series of patients with varicocele we found no mention of familial occurrence. Although the linkage between adolescent varicocele and spermatogenic dysfunction is still debatable, it is concluded from our experience that it is worthwhile examining other male members of families of affected adolescents or children but that expensive invasive studies are not warranted. PMID- 1589258 TI - The influence of perioperative transfusions on the immunological profile of patients with colorectal adenocarcinoma. AB - Seventy patients with Duke's C adenocarcinoma scheduled to undergo operation were divided into two groups, those who received no perioperative transfusion (Group I, 26 patients) and those who received an average of 2.1 units per person of packed red blood cells perioperatively (Group II, 44 patients). Immunological parameters were tested before and one and five weeks after the operation in order to determine the influence of the transfusion on these parameters as well as that of the site of the tumor, whether right colon, left colon or rectum. Comparison of the mean values obtained before operation with those obtained one week post operatively revealed a significant change in the number of B cells (p = 0.014), with a decrease in Group I and a rise in Group II, which was seen to persist for the mean values obtained five weeks after operation. The higher rates of recurrency and lower rates of survival reported in patients who received transfusion may be related to an as yet unidentified role of B cells or a subpopulation in the immune system, manifested in the suppression of activity of those components responsible for destroying micrometastases. In relation to the site of the tumor no definite conclusions can yet be drawn as to the prognostic importance of our findings concerning the immunological parameters. PMID- 1589259 TI - Effect of a pulsed magnetic field on AKR female mice offspring. AB - AKR mice were exposed to a 6 mT, 12 Hz or 460 Hz pulsed magnetic field for 30 minutes twice a week. The exposure took place in utero and/or during the life span for five consecutive generations. For the exposure the grown-up mice were put into a container which caused a restraint stress. That stress brought about lighter newborn mice and also a higher number of newborn mice which were to die. The exposure lessened the loss of weight due to the stress. It had no noticeable effect on the average numbers of newborn mice per litter, of dead newborn mice and on the sex-ratio. PMID- 1589260 TI - Environmental magnetic noise may be a health risk. AB - It has been demonstrated that magnetic fields stronger than those used in magnetic resonance imaging can be mutagenic, even teratogenic to the human genome. Recent experimental data has shown that magnetic fields ranging from the earth's steady magnetic field to the ten thousand gauss used in magnetic resonance imaging (MRI) can enhance oncogenic expression, among a variety of other effects both positive and negative. It is the purpose of this presentation to suggest that fields considerably weaker than the geomagnetic may have deleterious effects on the human genome, in addition to noting that very weak fields may also be physiologic. PMID- 1589261 TI - The journal Paraplegia. PMID- 1589262 TI - Fifty years on fundamentals in spinal cord injury care are still important. AB - The fundamentals of care in spinal cord injury were laid down many years ago. Prevention----therapy----follow up is basic in medicine. In spinal cord injury, admission to a comprehensive unit then application of simple, repetitive disciplines for patient and staff, and education are the fundamentals to be emphasised. The great pioneers, Munro, Guttmann and Botterell achieved advances long before sophisticated technology moved to a stage when now it could swamp hensive units catering for acute care but, more importantly, lifetime care with acceptance of the fundamental medical axis of prevention, therapy and follow up. The details of fundamental care include secondary and tertiary prevention techniques in hospital and community, and an acceptance by staff as well as spinal men and women of their simplicity, their repetitiveness, the need for disciplined action and the requirement for education at all levels. In the future, primary prevention must be given more emphasis as cure is many decades away even with the volume of basic research now being undertaken. PMID- 1589263 TI - Paraplegia: views from the Chief Scientist Office. PMID- 1589264 TI - The spinal cord injury primary physician. One riot--one ranger. PMID- 1589265 TI - Neural transplants in spinal cord injury. PMID- 1589266 TI - The evolution of the spinal cord unit: East and West. PMID- 1589267 TI - The way ahead. PMID- 1589269 TI - Spinal injury associations: a British perspective. PMID- 1589268 TI - Spinal injury in Scotland. PMID- 1589270 TI - The evolution of neuroimaging of spinal cord injury patients over the last decade. AB - A review is presented concerning the development of new neuroimaging techniques in the last decade which have improved the diagnostic exploration of patients with spinal cord injuries, including studies of possible sequelae. A number of technical developments occurred in the 1980s, which have broadened the diagnostic capabilities of neuroimaging and made its investigative techniques more precise and less invasive. In a summarized way the new or upgraded modalities such as magnetic resonance imaging and angiography, computed tomography and ultrasound, are considered here with regard to the effect that they have had on the clinical management of patients with a traumatized spinal cord. PMID- 1589271 TI - Spinal injuries: early surgical treatment. PMID- 1589272 TI - Conservative versus surgical treatment of the cervical and thoracolumbar spine in spinal trauma. PMID- 1589273 TI - Reflections on the International Medical Society of Paraplegia and management of paraplegia. PMID- 1589274 TI - Neurourology in spinal cord injured patients. PMID- 1589275 TI - Sexual dysfunctions in the spinal cord injured. PMID- 1589276 TI - Psychosocial research in spinal cord injury: the state of the art. PMID- 1589277 TI - Bioengineering developments for paraplegic patients. PMID- 1589278 TI - The current state of the management of the upper limb in tetraplegia. PMID- 1589279 TI - Progress of comprehensive rehabilitation of patients with spinal cord lesions in Germany 1962-1990. PMID- 1589280 TI - Rehabilitation: some thoughts on progress. PMID- 1589281 TI - Clinical rehabilitation research advances in spinal cord injury. PMID- 1589282 TI - Pharmacological treatment of acute spinal cord injury: current status and future prospects. AB - The history and results of the National Acute Spinal Cord Injury Studies (NASCIS) are briefly reviewed. The current status of pharmacological therapy for acute spinal cord injury and future prospects are also summarized. PMID- 1589283 TI - Community reintegration and quality of life following spinal cord injury. AB - This report contains a brief overview of issues related to community reintegration and quality of life for persons with spinal cord injuries. Current data from the National Spinal Cord Injury Statistical Center are provided on place of residence, employment, education and marital status after rehabilitation discharge. The health policy implications of these data are discussed along with prospects for continued improvement of long term social outcomes and directions for future research. PMID- 1589284 TI - Postural thixotropy: a significant factor in the stiffness of paralysed limbs? PMID- 1589285 TI - Pressure sores: a personal comment. AB - Pressure sores have always been with us and remain so. The care and prevention of sores in spinal injuries have shown a dramatic improvement over the past decade while for other categories this cannot be said. PMID- 1589286 TI - The role of intracavernous injection of vasoactive medications for the restoration of erection in spinal cord injured males: a three year follow up. AB - Fifty-eight spinal cord injured men entered our self injection program for restoration of erections since the program began in September 1985. Early complications included sustained erection (greater than 8 hours) in 4 patients on 6 occasions requiring aspiration of the corpora cavernosa and injection of a dilute epinephrine solution (1/100,000). Bruising at the site of injection was reported at least once by 10 patients. Blood draining from the urethra was noted in 3 patients when the urethra was inadvertently injected. Rigid erections were obtained in all but 5 patients that injected (90%). Late complications included penile plaque in 3 patients (15%). There were no abnormal liver function tests. Average time on the injection program was 2 years (range of 0.5 to 4.5 years). Thirty-one (53%) of the patients have dropped out of the program, most doing so prior to the first injection or during the titration period. The average frequency of injection was twice a month. Injection therapy remains an effective and relatively safe alternative for selective patients with spinal cord injury. PMID- 1589287 TI - The effect of intermittent positive pressure breathing on lung volumes in acute quadriparesis. AB - Resting tidal volume and vital capacity were measured daily in 5 patients with acute quadriparesis during the first 7 to 10 days of their hospitalisation. On admission, vital capacity was significantly reduced to 26% of the predicted value (p less than 0.001). This increased significantly over the study period to 33% of the predicted value (p less than 0.02). Expiratory flow rates, measured on one occasion during the study period, showed similar decrements. Tidal volume and vital capacity were also measured immediately following administration of intermittent positive pressure breathing (IPPB). Although the lung volume achieved during IPPB was significantly higher than resting values of tidal volume and vital capacity (p less than 0.001), tidal volume returned to baseline values as soon as IPPB was ceased. Vital capacity remained significantly higher than baseline values at this stage (p less than 0.02), although the mean increase in vital capacity immediately following IPPB was only 43 mls. Acute quadriparesis is associated with a severe ventilatory impairment which includes a reduced vital capacity and expiratory flow rates. IPPB has a positive effect on lung volume whilst it is being administered. Immediately following treatment, this effect does not appear to be sustained at a level which would be considered clinically significant. PMID- 1589288 TI - The effect of intravesical Marcain instillation on hyperreflexic detrusor contractions. AB - Thirty-six patients with suprasacral spinal injury were treated with intravesical local anaesthetic instillation. Eighteen of 32 patients (56%) were converted from an 'ice water positive' hyperreflexic state to an 'ice water negative' state by bupivacaine hydrochloride. Four patients treated with lignocaine hydrochloride showed no benefit. Intravesical local anaesthetic instillation is suggested as a possible treatment for selected cases of detrusor hyperreflexia in patients on intermittent catheterisation. PMID- 1589289 TI - Long term follow up of spinal cord injury caused by penetrating missiles. AB - Eighty-four spinal cord injured patients (SCIP) injured as a result of penetrating missiles were categorised according to: neurological level of injury, age at time of injury, circumstances of injury, missile type, initial treatment, duration of injury, and ethnic background. Evaluations and comparisons were made concerning: life habits, family status, education, employment, and mental well being. A discussion of complicating factors, both physical and psychological, and their relation to the final rehabilitation result is presented. PMID- 1589290 TI - The management of spinal cord injury patients in Greece. AB - In Greece, spinal cord injury patients have serious problems concerning their treatment, social management and vocational integration. Unfortunately the treatment of such patients is usually limited to that offered in institutions for the chronically sick, after they have received their acute initial care in general hospitals. The large number of institutional beds (1287 in 1986) in relation to the small number of active rehabilitation beds (116 beds in 1989) is noteworthy. Generally speaking, the specialisation of health personnel is limited. In practice there is no programme of social rehabilitation, except for special concessions. Disabled individuals can refer to the Professional Integration Service for their vocational reintegration. We must note that vocational counsellors do not take part in the rehabilitation team. The idea of intervention for the adaptation of architectural barriers is now beginning to be considered in theory. Physicians are making efforts to establish 'basic' spinal cord units. PMID- 1589291 TI - Spinal cord injury due to suicide attempts. AB - During 1965 to 1987 45 patients were admitted to the Rehabilitation Hospital in Hornbaek, Denmark because of spinal cord injury (SCI) due to suicide attempts. The proportion of traumatic SCI due to this cause increased significantly during the period: 1965-74: 3.5%, 1975-84: 8%, 1985-87: 13%. The median age at injury was 31 years, and the female to male ratio 1.6. In 38 instances (84%), SCI was caused by jumps from buildings. The neurological level of the lesion was: 7 cervical, 8 thoracic, 22 lumbar; the remaining 8 had minor spinal cord/cauda equina lesions. At the time of the SCI 62% were unemployed or receiving an early pension; 60% were living without a partner; 62% had previously been admitted to psychiatric hospitals, and 31% had previously attempted suicide. A follow up study was conducted in 1988-89. At follow up 11 patients had died, 3 from suicide. Of the 34 alive at follow up, 7 had attempted suicide, and 2 reported suicidal thoughts; 71% were living without a partner; 9% were employed; 18% abused alcohol; 44% had had a psychiatric admission since the SCI; and 56% were taking psychiatric medication. PMID- 1589292 TI - Spinal cord injuries: the last decade and the next. PMID- 1589293 TI - Spinal cord repair: future directions. AB - The main cause of disability following spinal injury is failure of axons to regenerate and reconnect the spinal cord with the brain. If patients with cord lesions are ever to make a full recovery some means will have to be found to restore ascending sensory and descending motor connections. Until the last few years there has been a very limited understanding of the reasons why axons in the central nervous system (CNS) fail to regenerate, but as a result of recent work the picture is now much clearer. PMID- 1589294 TI - Indian spinal injuries centre. AB - A 110-bedded spinal injury centre is under construction in New Delhi. This centre will be equipped through Indo-Italian friendship with the latest medical and technical equipment. The centre will be ready in September 1992 for the treatment of acute injuries from Delhi and surrounding areas and will treat complicated cases referred by other centres/hospitals in India. Research and training of doctors, nurses and rehabilitation staff will be an integral part of the centre. PMID- 1589295 TI - New spinal cord injury standards, 1992. PMID- 1589296 TI - Development of neurophysiological aspects of the spinal cord during the past ten years. PMID- 1589297 TI - Neural prostheses: clinical applications of functional electrical stimulation in spinal cord injury. AB - Function lost in spinal cord injury can be partially restored in some patients by electrical stimulation of remaining neurons. Neural prostheses designed for this purpose have been under development for several decades and are now in increasing clinical use. Applications are outlined for restoration of respiration, bladder, bowel and sexual function, exercise, hand grasp and standing and walking. PMID- 1589298 TI - Immuno-epidemiology of human geohelminthiasis: ecological and immunological determinants of worm burden. AB - The morbidity and transmission dynamics of geohelminthiases are determined by the patterns of infection intensity in the community. Understanding the determinants of these patterns requires a combination of field, laboratory and theoretical study. Studies of age-specific reinfection, and of the phenomenon of predisposition, indicate that the major determinant of convex age-intensity profiles and of heterogeneity in infection intensity is the rate of establishment of infection, rather than the rate of adult worm mortality. The rate of establishment is, in turn, determined by exposure to, and protection from, infection. The evidence indicates that exposure, at least to the orally transmitted geohelminths, varies with age and is highly heterogeneous between hosts. The immune response in geohelminthiasis is vigorous, parasite-specific, heterogeneous between hosts, and both age and infection dose dependent, but has yet to be convincingly shown to be protective. Since the immune response it itself a function of exposure, unravelling the interaction between ecology and immunology as determinants of geohelminth worm burden will require simultaneous assessment of both processes via immunoepidemiological study. PMID- 1589299 TI - Population genetics and dynamics of Plasmodium falciparum: an ecological view. AB - Molecular characterization of the Plasmodium falciparum genome has led to identification of polymorphic loci and the mechanisms generating genetic diversity in this parasite. This information has resulted in the development of molecular methods to type parasite diversity in the field. Consequently, we are now in a position to describe the population genetics and dynamics of P. falciparum. The limited number of field studies that have been conducted to date have revealed an extraordinary degree of genetic diversity in natural parasite populations. Heterozygous recombination which occurs during meiosis appears to be one mechanism for generating genetic diversity. The rate at which such recombination occurs in natural parasite populations defines the genetic structure of the parasite population and can influence the ability of the parasite to respond to selection pressure. The high frequency of single genotype infections and the female-biased gametocyte sex ratios found in hyperendemic malaria areas suggest that self-fertilization occurs frequently. Population-wide surveys of allele frequencies in endemic areas have, however, shown no evidence of linkage disequilibrium and are consistent with a panmictic population structure. We argue that these studies have only sampled symptomatic infections, within which rare or recombinant genotypes may be disproportionately represented. They also take no account of the spatial structure of P. falciparum populations. Systematic investigations of the amount of heterozygosity in small areas as part of population-wide surveys are required to define the genetic structure of P. falciparum populations. Population dynamic studies which consider genetic heterogeneity of P. falciparum have shown fluctuations of different serotypes in space and time. The host immune response appears to play an important role in generating these dynamics. Integrated field and laboratory studies, which consider the interaction between population genetics and dynamics, will be necessary to describe the population biology of P. falciparum. PMID- 1589300 TI - Malaria--a neglected disease? AB - In situations where malaria eradication is not an option in the foreseeable future the emphasis must be on the control of morbidity and mortality due to malaria. Under such circumstances drawing a distinction between malarial parasitization and malarial disease may be important for workers in both field and laboratory. This concept is explored from the points of view of the epidemiological picture of malaria in endemic populations, the factors which may influence progression to disease and the processes which mediate disease. PMID- 1589301 TI - Leishmaniasis epidemiology: the theory catches up. AB - Until recently, almost all studies of leishmaniasis epidemiology were qualitative and descriptive. But now that the natural history of many Leishmania parasites is quite well known, there is growing interest in quantitative analysis. In this paper I use mathematical models in conjunction with field data to try to answer a wider range of questions than has previously been possible with descriptive techniques, and to sharpen some of the outstanding questions for laboratory workers. This is done with reference to the persistence and resilience of canine leishmaniasis, the maintenance of virulence polymorphisms in Leishmania populations, and the possible existence of cycles of human kala-azar. I conclude by posing a set of problems under three headings: diagnosis of infection (as distinct from disease), natural immunity to Leishmania infection in the vertebrate host, and genetic variation in the parasite population. Some solutions from the laboratory can be found in the companion paper by Blackwell (1992). PMID- 1589302 TI - The Wellcome Trust Lecture. Infection and disease in lymphatic filariasis: an immunological perspective. AB - The basic tenet of the immunological perspective of filarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of 'asymptomatic microfilaraemia', who have been previously described as being 'immunosuppressed' with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the 'immunosuppressed' state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the 'natural history' of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589303 TI - Infection and disease in lymphatic filariasis: an epidemiological approach. PMID- 1589304 TI - Intestinal nematode infections in children: the pathophysiological price paid. AB - The mechanism by which small animals such as rodents resist or eliminate nematode parasites requires mucosal inflammation as the final effector of the immune response. The resulting freedom from chronic infection may be worth the price of short-term illness. Putative vaccines which attempt to enhance the natural effect will have to take into account the inflammatory cost to the host. Human helminthiases involve a more stable equilibrium between host and parasite. The medical literature on hookworm disease and clinical ascariasis describes, for the former, some chronic inflammatory effects correlated with worm burden, but for the latter a less quantified or predictable set of detrimental effects. We describe a current, systematic study of the inflammatory response to whipworm infection, in which anaemia, growth retardation and intestinal leakiness are viewed as predictable consequences related to infection intensity. There is evidence for the absence of cell-mediated immunopathology. However, a specific, IgE-mediated local anaphylaxis may, at least partly, mediate the deleterious effects. Increased numbers of mucosal macrophages may also contribute to the chronic, systemic effects through their output of cytokines. Similar attempts to show the mechanisms of pathogenesis and quantify the effects of hookworm disease should be undertaken. PMID- 1589305 TI - The conundrum of wheezing and airway hyperreactivity in infancy. PMID- 1589306 TI - Prediction of the acute response to surfactant therapy by pulmonary function testing. AB - We tested the hypothesis that pretreatment pulmonary function values would be predictive of the response to the synthetic pulmonary surfactant, Exosurf (Burroughs Wellcome Co.) treatment of infants with respiratory distress syndrome (RDS). Pulmonary compliance and resistance were measured prior to Exosurf treatment in 40 infants with severe RDS. In 36 patients who survived for at least 24 hr the acute response to therapy was quantitated by calculated post treatment/pretreatment ratios of ventilator efficiency index (VEI) and arterial/alveolar oxygen tension ratios [Pa/AO2]. The values of these calculated response ratios 24 and 48 hr after treatment varied widely among individual patients. The magnitude of the response was not related to birthweight, gestational age, age at treatment, pretreatment VEI, pretreatment Pa/AO2, or pretreatment pulmonary compliance. However, the response to Exosurf as measured by improvements in Pa/AO2 at 24 and 48 hr was related to pretreatment pulmonary resistance (r = -0.34, P less than 0.05 and r = -0.60, P less than 0.001), high pretreatment pulmonary resistance was associated with a poor response to Exosurf 24 and 48 hr after treatment. PMID- 1589307 TI - Comparison of nap and overnight polysomnography in children. AB - Overnight polysomnography is the "gold standard" for diagnosing sleep-disordered breathing. However, the limited number of resources for pediatric polysomnography make the availability of a screening test for sleep-disordered breathing highly desirable. Therefore, we compared 1 hour daytime nap polysomnography to overnight polysomnography in 40 children [mean age, 5.4 +/- 0.8 (SE) years] with sleep disordered breathing; 76% of children were sedated with chloral hydrate for nap polysomnography; none was sedated for overnight polysomnography. Studies were done 26 +/- 4 days apart. Chest wall motion, ECG, end-tidal PCO2 (PETCO2), arterial oxygen saturation (SaO2), and electrooculogram were monitored. Nap studies had a sensitivity of 74%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 17% in predicting sleep-disordered breathing. Significantly more children had obstructive apnea and desaturation (SaO2 less than 90%) during overnight polysomnography. The peak PETCO2 and the SaO2 nadir were significantly worse during overnight polysomnography. However, the percentage of time during which abnormalities were manifested did not differ between nap and overnight polysomnography. Despite the use of sedation, nap polysomnography underestimated sleep-disordered breathing. We conclude that sleep disordered breathing detected by nap polysomnography is always confirmed by overnight polysomnography and speculate that nap polysomnography may be an effective screening method for sleep-disordered breathing. However, overnight polysomnography should be performed if nap polysomnography is inconclusive. Chloral hydrate may be used effectively to facilitate sleep for nap polysomnography in children. PMID- 1589308 TI - Phospholipid composition and surface-active properties of tracheobronchial secretions from patients with cystic fibrosis and chronic obstructive pulmonary diseases. AB - Among the various components of tracheobronchial secretions, lipids and particularly phospholipids have been shown to influence rheological properties of airway secretions in patients with cystic fibrosis. We studied the phospholipid composition of tracheobronchial secretions, collected from patients suffering from cystic fibrosis (CF) and other chronic obstructive pulmonary diseases (COPD), and we analyzed the possible relationship between the phospholipid profile and the wettability of tracheobronchial secretions evaluated by the measurement of contact angle. Although total phospholipid content and contact angle of tracheobronchial secretions were significantly increased (P less than 0.01) in CF compared to COPD, no significant relationship existed between these two parameters. The concentrations of the different phospholipid subclasses were not homogeneously modified according to the origin of the secretions. Compared to COPD secretions, the CF secretions were characterized by a significant (P less than 0.001) increase in rigidifying fractions such as sphingomyelin and phosphatidylserine/phosphatidylinositol and a significant (P less than 0.001) decrease in surface-active fractions, such as phosphatidylcholine and phosphatidylglycerol (PG) (P less than 0.001). In the two groups, the surface active phospholipid fraction, PG, was negatively correlated to the contact angle of tracheobronchial secretions. These results suggest that a decrease in PG content in CF secretions may be one factor responsible for an increase in their adhesivity to the respiratory mucosa, and, consequently, for mucus stasis and severity of bronchial obstruction in cystic fibrosis. PMID- 1589309 TI - Mechanical properties of the upper airway wall in children and their influence on respiratory impedance measurements. AB - The upper airway wall impedance (Zuaw) may be responsible for a large artifact in the measurement of respiratory system impedance (Zrs) in children. In 17 normal children aged 3.5-13 years Zuaw and Zrs were estimated by varying transrespiratory pressure directly at the mouth (conventional method: Z1) and around the subject's head (head generator method: Z2) from 4 to 32 Hz. Zrs and Zuaw were calculated from Z1 = Zrs.Zuaw/(Zrs+Zuaw) and Z2 = Zrs (1 + Zp/Zuaw), where Zp is the impedance of the pneumotachograph. From the real and imaginary part of Z1, Z2, Zrs, and Zuaw, the corresponding resistance, inertance, compliance and resonant frequency were calculated assuming simple RIC models. No significant difference was found between the mean +/- SE of parameters derived from Zrs (respectively, 6.8 +/- 0.4 cmH2O.L-1.s, 0.034 +/- 0.001 cmH2O.L-1.s2, 10.4 +/- 0.8 m.cmH2O-1, 9.1 +/- 0.3 Hz) and Z2 (6.8 +/- 0.4 cmH2O.L-1.s, 0.038 +/ 0.002 cmH2O.L-1.s2, 10.7 +/- 0.7 ml.cmH2O-1, 8.7 +/- 0.4 Hz). All but the compliance, derived from Z1 were significantly different (P less than 0.01) from those derived from Zrs (5.3 +/- 0.3 cmH2O.L-1.s, 0.008 +/- 0.001 cmH2O.L-1.s2, 11.9 +/- 1.2 ml.cmH2O-1, and 20.3 +/- 1.6 Hz). Respiratory resistance and compliance correlated significantly with height (r = -0.56 and 0.86, respectively), in contrast to upper airway wall resistance (Ruaw) and compliance (Cuaw). Ruaw (8.6 +/- 0.8 cmH2O.L-1.s), Cuaw (1.2 +/- 0.2 m.cmH2O-1), and upper airway wall inertance (0.030 +/- 0.004 cmH2O.L-1.s2) were close to those obtained by direct measurements in adults. The mechanical properties of the upper airway wall are responsible for a significant error in the measurement of Zrs by the conventional method in normal children. Most of the artifact may be corrected for by applying pressure around the child's head. PMID- 1589310 TI - Nonbronchoscopic approach to bronchoalveolar lavage in children with artificial airways. AB - Bronchoalveolar lavage (BAL) performed with a fiberoptic bronchoscope (FOB) is a useful method for sampling alveolar contents. Since the smallest FOB with a channel has a diameter of 3.6 mm, BAL is difficult to accomplish through artificial airways (AA) less than 5.0 mm I.D. We used a 4F balloon wedge pressure catheter to perform BAL through small AA. Supplemental O2 or ventilatory support was delivered via an adaptor through which the catheter was introduced. After it was passed distal to the AA, the balloon was inflated with normal saline (NS) to a predetermined volume, and advanced until resistance was felt. The balloon was deflated, advanced slightly, and then reinflated to achieve airway occlusion. Five aliquots of 0.75 mL/kg of NS were used for BAL. The procedure was performed in 20 children from 1 month (950 g) to 6 1/2 years of age (median, 9 months). All specimens contained abundant alveolar macrophages, indicating good recovery of alveolar contents. Clinically significant information was obtained in 17 (85%) cases, and no patient required an open lung biopsy. In conclusion, nonbronchoscopic bronchoalveolar lavage is a valuable method for obtaining alveolar contents in children with small AA that preclude the use of an FOB, and it obviates the need for open lung biopsy in many patients. This technique could be used as a research tool for measuring constituents of alveolar contents in infants and small animals. PMID- 1589311 TI - A superficial view of mucus and the cystic fibrosis defect. PMID- 1589312 TI - A radiographic method for estimating lung volumes in sick infants. AB - Estimation of lung volumes by conventional methods in sick infants is technically difficult and is the subject of controversy. In this study, we compared both thoracic gas volume (TGV), measured with an infant whole body plethysmograph, and functional residual capacity (FRC), determined by the nitrogen washout technique, to planimetric measurements of anteroposterior chest radiographs in 26 infants with bronchopulmonary dysplasia (BPD). The tidal volume (TV) of each patient was added to TGV and FRC because these were measured at the end of expiration whereas chest radiographs were taken at the end of spontaneous inspiration. The regression equations expressing the relationships between TGV and right+left lung field areas [A+B], and between FRC and lung areas are expressed as follows: [TGV+TV](mL) = 3.3 mL/cm2 x [A+B] cm2 + 24 mL and [FRC+TV](mL) = 3.5 mL/cm2 x [A+B] cm2 - 13.5 mL. Correlation coefficients of 0.9 and 0.7 for TGV and FRC, respectively, suggest a stronger correlation between TGV and lung areas than between FRC and lung areas. Lung areas measured by planimetry correlate closely with physiological measurement of lung volumes. We conclude that the planimetric method is an inexpensive and reliable technique for estimating lung volumes in young infants with BPD when chest radiographs are available. PMID- 1589313 TI - Ultrathin fiberoptic bronchoscopy for airway toilet in neonatal pulmonary atelectasis. AB - Pulmonary atelectasis is often seen in young infants with respiratory disease and it may contribute to increased ventilatory requirements and the development of chronic lung disease such as bronchopulmonary dysplasia. Standard management consists of postural drainage (chest physiotherapy and suction) and selective intubation with suction of a major bronchus. This report describes a new approach consisting of removal of bronchial secretions under direct vision via ultrathin fiberoptic bronchoscopy, without interruption of mechanical ventilation. The procedure was performed safely in ten cases and resulted in significant rapid improvement in the infants' respiratory condition and in complete resolution of the atelectasis in eight cases. In two infants, partial improvement was seen. No adverse effects of the procedure were encountered. It is concluded that this approach is a safe and potentially valuable therapeutic maneuver in the management of pulmonary atelectasis in sick intubated neonates. PMID- 1589314 TI - Partial and massive lung lavages in an infant with severe pulmonary alveolar proteinosis. AB - Pulmonary alveolar proteinosis is a rare disease of unknown etiology, characterized by progressive respiratory failure. Lung lavage has only been applied in a few children. A 6 month old boy suffering from severe pulmonary alveolar proteinosis was treated with three lung lavages. The first two were partial (or unilateral) lavages; a 3.5 mm flexible bronchoscope was introduced adjacent to a no. 3 cuffed endotracheal tube. This procedure allowed selective ventilation of one lung, and contralateral lung lavage. Respiratory improvement was observed during 1 week after the two procedures. At the third lavage we used partial veno-venous extracorporeal circulation because of severe respiratory failure. A significant improvement during the 5 following months was achieved. These results suggest that both partial and total lung lavage can be performed even in young infants and they may control the declining respiratory status in severe pulmonary alveolar proteinosis. PMID- 1589315 TI - Compact apparatus for measurement of ventilatory response to carbon dioxide in newborns and infants. AB - We developed a rebreathing system for measuring response to carbon dioxide (CO2) of newborns and infants for use at the bedside. The system based on Read's method is small, easy to operate, and includes a computer-controlled gas switching sequence, computerized calculation, and display functions. We measured the CO2 response in 11 infants with or without apnea, who were born at 26-33 weeks gestation and were 12 to 215 days old at the time of the study. Our results suggest that the presence of apnea in premature infants may correspond to a low CO2 response. The method was convenient for clinical use because it allowed an investigator to carry out bedside tests in only a few minutes. With our system we were able to assess respiratory center function in newborns and infants. PMID- 1589316 TI - Airway responsiveness in infants following bronchiolitis. AB - Airway responsiveness to inhaled methacholine was assessed in 18 infants, 4 and 10 months old, following bronchiolitis. Pulmonary function was measured from partial expiratory flow-volume curves generated by the rapid compression technique. Sleeping infants inhaled increasing concentrations of methacholine until maximal expiratory flows at functional residual capacity (VmaxFRC) decreased by 30% or 2.5 mg/mL was inhaled. Airway responsiveness was quantitated by: 1) the threshold concentration (log TC) required to decrease VmaxFRC by 2 standard deviations from baseline; 2) the concentration required to decrease VmaxFRC by 30% (log PC30); and 3) the slope of the dose-response curve between TC and PC30 (log SPC30). At both the first and second evaluation, the bronchiolitic infants had lower baseline VmaxFRC (% pred.) than 24 control infants. In addition, the bronchiolitic infants had heightened airway responsiveness compared to controls, demonstrating lower values for logTC and logPC30 and steeper slopes to their dose-response curves (logSPC30). After accounting for the relationship between airway responsiveness and age, the occurrence of bronchiolitis was found to be a significant independent factor 10 months but not 4 months following bronchiolitis. The bronchiolitic infants did not demonstrate the decline in airway responsiveness with increasing age that occurs in normal infants. We conclude that infants exhibit heightened airway responsiveness following bronchiolitis. PMID- 1589317 TI - On surfactant replacement therapy with Exosurf. PMID- 1589318 TI - On sudden severe bradycardia in infancy. PMID- 1589319 TI - Diversity: what does it mean? PMID- 1589320 TI - The NIH strategic plan: how will it affect the future of nursing science and practice? PMID- 1589321 TI - Growing edges of a new paradigm: the future of nursing in the health of the nation. AB - Areas of growth in nursing are to be found at the points of interprofessional and community contact. The principles of primary health care can guide us toward empowerment to seek "Health for All." PMID- 1589322 TI - Feminism and nursing knowledge: the power of the weak. PMID- 1589323 TI - Contributions of Martha Rogers to the development of nursing knowledge. AB - Martha Rogers' greatest contribution may be her introduction into nursing of a questioning stance about the prevailing models of science, leading to increased acceptance of alternative paradigms, a variety of research methods, and explorations of topics such as existentialism and Eastern philosophy. Nursing is a richer, more diverse profession because of Martha Rogers. PMID- 1589324 TI - Building administrative support for your research: a neglected key for turning a research plan into a funded project. AB - There is more to grantsmanship than writing a good proposal. Planning, building, and negotiating administrative support may make the difference in a successful research effort. PMID- 1589325 TI - Improving retention and graduation rates for black students in nursing education: a developmental model. AB - High attrition rates among black students are a significant factor in the decline in graduation rates from nursing programs. Nursing education needs a program to address problems of anger, frustration, and loneliness and to develop the black student as a whole person. PMID- 1589326 TI - Cheating: faculty responsibilities when integrity fails. PMID- 1589327 TI - HIV and HBV in health care workplace investigated. PMID- 1589329 TI - Current status of the Ventak PRx pulse generator and Endotak nonthoracotomy lead system. PMID- 1589328 TI - HIV-positive nurses should continue to practice, ICN says. PMID- 1589330 TI - [Extrauterine adaptation: cardiac output changes in different modes of delivery. Preliminary results]. AB - Cardiac output in two homogeneous populations of term newborns, by spontaneous delivery and cesarean section without labour, has been estimated at 2, 24, 48, 72 and 96 hours after birth. Changes has been noticed in Cardiac Output in the first day of life and between different mode of delivery. Larger charges has been noticed in spontaneous then in cesarean delivery. PMID- 1589331 TI - [Controversial aspects and rational bases of the treatment in neonatal jaundice]. AB - High serum bilirubin levels (SBL), over 20-25 mg/dl are toxic for the Central Nervous System (CNS) of newborn infants. However, the possible toxicity on the CNS of "intermediate" SBL both in term and preterm neonates are still a matter of debate. An extensive review of the literature in this respect did not provide conclusive evidence for a dose-response pattern of toxicity for SBL 18-20 mg/dl in infants without hemolysis and/or other risk factors (such as extreme prematurity, hypoxia, hypercapnia, acidosis, sepsis, hyperosmolarity, etc.). Therefore, an aggressive approach to the treatment and/or prophylaxis of neonatal jaundice when SBL are below 20 or even 25 mg/dl is not justified on the basis of the present knowledge. This is particularly true when treatment includes phototherapy and/or exchange-transfusion which are associated with clinically significant complications and side effects. Guidelines for treatment of neonatal hyperbilirubinemia in full-term and preterm infants, with and without added complications and/or risk factors, are provided in the attempt of encouraging a more critical approach to neonatal jaundice, which is coherent with the data available in the literature and which should optimize the risk/benefit ratio. PMID- 1589332 TI - [Influence of the delivery on neonatal competence]. AB - It is a widely held view that the NBAS (Brazelton, 1973) can index differences in the level of the neurobehavioural organization of both pathological and normal newborns. The present study employed the NBAS to determine whether the type of delivery, i.e. cesarean or spontaneous vaginal, can influence the level of neurobehavioural organization in the first days of life. To this aim, two groups of healthy newborns, as assessed through obstetrical anamnesis and the Apgar index, were compared at 4, 24, 72 hours of postnatal life. Ten newborns were born by cesarean section and 10 were born by spontaneous vaginal delivery. The results did not show any neurobehavioural differences for the five clusters of the NBAS: Response decrement, Orientation, Motor, Range and Regulation of states. This outcome fails to support the hypothesis that the level of neurobehavioural organization in the first hours of postnatal life depends on the type of delivery. It must be considered, however, that the null results could be attributed to the way the NBAS is administered according to Brazelton's criteria of "best performance" and "flexibility of the examiner". In essence, these criteria require the NBAS to be administered several times in succession, by varying the order of clusters and the order of items within a cluster, until the "best performance" is obtained. Therefore, a second experiment was conducted, in which the criticisms and suggestions put forward by Prechtl (1982) were taken into account. Two groups of 10 newborns each, selected as before, were tested.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589333 TI - [Preterm labor: timing and management]. AB - Premature rupture of membranes and intrauterine growth retardation are the most frequent conditions in which preterm labour and delivery may be facilitated or induced. If the membranes ruptured before 34 weeks, pregnancy may be prolonged for more than one week and premature fetus perhaps might benefit of steroid administration for the prevention of respiratory distress syndrome and of antibiotic preventive treatment. After 33 completed weeks no prolongation of gestation for more than one week seems to be particularly useful for newborn survival. Actually, intrauterine growth retardation and fetal chronic distress may be prematurely diagnosed (sonographic and Doppler diagnosis, non stress test, ecc.). Antepartum fetal evaluation and management of pregnancy with poor intrauterine growth are problems that need multidisciplinary measures, but the timing and the modality of delivery are strictly obstetric decisions. In case of fetal malformations and/or in case of extremely premature low-weight infants, management and timing of preterm labour and delivery need a particular care in observance of the well-being and of the outcome of these babies. PMID- 1589334 TI - [Early diagnosis of intellectual deficiency]. AB - The Author reports the results of some studies of the developing cognitive competences in infants. Utilizing the Hz-giris-Hunt's and the Brunet-Lezine's Scales in 18 infants during the two first months of life did not observe significant correlation between neurologic examination and development of cognitive competence. In an other study of 52 infants of less than two months old, with or without perinatal brain damage, the attentive motricity resulted to be predictive index of future cognitive abilities until twelfth month of age. PMID- 1589335 TI - [Computerization of a clinical chart of perinatal data]. AB - A computerized protocol, PADOVA-BPD, has been set-up to study prematures affected by RDS, PDA and/or BPD. This protocol consists of a Data Bank, BPDdata, where the information of traditional clinical chart has been stored and of the BPDPadova program, written for this purpose in FORTRAN 77, that allows a wide band of clinical and statistical analysis. PMID- 1589336 TI - [Obstetric/neonatological integration and care of healthy newborn infants]. AB - We report how we changed the model of the organization and the assistance in our Department of healthy newborns (2200-2400/years). After we have realized that mothers were not satisfied of the rules of the hospital and personnel was not satisfied of the job, we decided to begin a process of analysis and review of the procedures on full term newborn. During this process we found out that the most important thing was to have clear in mind the problems and the needs of the mother and the baby, and not those of nurses and doctors. A similar process took place in the Department of Obstetrics. In this way we, Obstetrics and Neonatologist together, began to offer a more human approach to birth, and rooming-in began. We stopped to attend every normal delivery, to separate immediately mother and baby, to feed the baby at fixed time, to give him supplementations. We tried to have with the mother a better relationship, visiting the baby in presence of the mother an receiving grom Obstetrics as soon as possible every information about pregnancy. We realized that this was possible only if the Neonatologist and the Obstetric were of the same opinion about a more human approach to birth. We stress this point, well aware that it's impossible to reach this goal unless everybody in any way involved in birth work in great harmony with all the others. A further result of this "new" way of working has been the program of early discharge: if desired, and whenever possible, the mother and the baby go home 48-72 hours after delivery. We report here preliminary data. PMID- 1589337 TI - [Experience in labor and delivery care in university centers]. AB - Some considerations about an individual experience of labour and delivery care by means of three different partograms at the university departments of Obstetrics and Gynecology of Genova, Trieste and Verona are reported. The value of partography in management of labour was stressed in connection with a better delivery care, with a systematic recording of cervicometric data and fetal maternal monitoring and in the prevention of the use of unsuitable medical and surgical treatments. The partogram is also essential for the correct communication and makes both tracking and data filing easier. By means of partography the return concept of personalized care of woman in labour is possible without that safety and technology of new obstetrics are lost. PMID- 1589338 TI - [Prostacyclin in the treatment of persistent fetal circulation syndrome]. AB - Persistent pulmonary hypertension of the neonate (PPHN), described initially by Gersony in 1969 as persistent foetal circulation (PFC syndrome), results from a flawed transition from foetal to extrauterine pulmonary circulation. It is primarily characterised by persistence of, or return to, the suprasystemic pulmonary vascular resistance and pressure normally found in the foetus. The increased pulmonary pressure causes right to left shunting through the ductus arteriosus or the foramen ovale, or both. The resulting hypoxaemia and acidosis may produce further pulmonary vasoconstriction and lead to a vicious cycle of shunting, hypoxia and acidosis. Infants with a wide variety of underlying clinical conditions develop PPHN. This condition is reversible, but can cause very severe and unrelenting respiratory failure and ultimate death when uncontrolled. Although vasodilating agents, such as tolazoline, have been used with variable success in the treatment of PPHN, a generally acceptable therapy is still lacking. We report here the use of prostacyclin (epoprostenol, PGI2) in two infants with severe and refractory hypoxaemia secondary to pulmonary vasoconstriction. PMID- 1589339 TI - [Incidence and significance of heart murmurs in newborn infants admitted to nursery]. AB - In a retrospective study on heart murmurs in healthy newborns we reviewed data concerning all newborns admitted in our nursery in the year 1990 (1387 newborns: male 699, female 688). An heart murmur was recorded in 106 (7.6%); in 32 of these (30%) the murmur was still audible at discharge; in 18 cases (17%) a congenital heart defect was diagnosed. Our data suggest that time of onset and intensity are valuable data for diagnostic approach, as murmurs recorded after the first day of life, and/or of intensity of 2/6 or more, are more likely to be expression of a congenital heart disease and should be further evaluated. PMID- 1589340 TI - [Postpartum adaptation of naturally delivered newborn infants. Preliminary results]. AB - We report the preliminary data referring to a controlled study on the post-partum adaptation of the naturally delivered newborn. Apart from a greater incidence of benign jaundice, no differences have been found to date between the traditionally and naturally delivered neonates. PMID- 1589341 TI - [Monitoring of body temperature during fiber optics phototherapy]. AB - Fiberoptic phototherapy is a new technique for treatment of neonatal hyperbilirubinemia; in comparison with conventional phototherapy this new technique shouldn't increase body temperature during treatment. We have recorded body temperature of 13 term newborns with hyperbilirubinemia during 18 periods of treatment and compared the records with physiologic body temperature in the same babies. No increase over normal value during treatment nor significative difference during and after treatment has been observed. PMID- 1589342 TI - [Bacterial ecology in a neonatal intensive care unit]. AB - A study about bacterial colonization/infection has been performed in 523 newborn, consecutively hospitalized in the Neonatal Intensive Care Unit (NICU) of Verona. Bacteriological samples were taken routinely at the admission in all patients and selectively only in neonates at risk of infection. The obtained data revealed a significative prevalence of gram-positive organisms (particularly Staphylococcus epidermidis highly resistant to antibiotics commonly used); among gram-negative bacteria Pseudomonas spp. resulted the more frequently isolated micro-organisms. According to data obtained, antimicrobial approach to bacterial infection in our NICU is finally discussed. PMID- 1589343 TI - [The preterm infant in the nursery?]. AB - We evaluated 250 newborns, GA less than or equal to 37 weeks, admitted to the Nursery of the Pediatric Department of Padua, between 1.1.1990 and 31.7.1991. We considered particularly three groups of newborns with 35, 36 and 37 weeks gestation respectively. Other 80 fullterm newborns were included in the study as control group. The postnatal adaptation (table 1) is regular in 96.2% of the fullterm newborns, and in 62.9% of the 35 wks. Jaundice is the main cause of irregular postnatal adaptation in the preterm newborns (22.8% in the 35 wks group, and 16% of the control group). When we considered the feeding modalities (table 2), we found that only the 21.7% of the 36 wks group and the 11.4% of the 35 wks group were breast fed, against the 86.3% of the control group. The discharge from the Nursery was earlier (less than or equal to 4th day of life) in the term groups and later in the preterm, who often stay in the Nursery for a longer period because of their feeding, growth and postnatal adaptation problems. These results could be certainly improved introducing the rooming-in method, which at the moment is not fully applied in our Nursery. PMID- 1589344 TI - [Neonatal neuro-behavior assessment scale. Theoretical premises for its use in preterm newborn infants and model of intervention]. AB - A model for preventive intervention based on the use of the Neonatal Behavioral Assessment Scale (NBAS) with prematures is presented, and the conceptual framework underlying this approach is made explicit. The approach is based on the assumption that the neonatal period presents clinicians with a unique opportunity to influence parent-infant relationship positively from the beginning. The model of intervention described herein is based on the development of a supportive therapeutic relationship between clinicians and parents and as much may serve as the first stage in a comprehensive follow-up program of support for infants and families. PMID- 1589345 TI - [Modalities of adaptation to extrauterine environment of newborn infants during sleep]. AB - Three groups of healthy full term neonates, differing in delivery modalities (elective caesarean section, labor of greater than or less than 7 hours) were investigated during sleep to evaluate postnatal adaptation. Adaptation modalities were assessed by NBAS, using the cluster of the decrements. It was found that neonatal responses change during sleep in relation to delivery modalities and to type of stimuli applied. PMID- 1589346 TI - [Breast feeding of the premature infant in nursery]. AB - The Authors considerate the incidence of breast feeding in healthy preterm neonates. They emphasized the high incidence in breast feeding after discharge from the Nursery. PMID- 1589347 TI - Metastatic bone disease: philosophy of treatment. PMID- 1589348 TI - Impending fracture associated with bone destruction. AB - In the patient with metastatic bone disease, destruction of bone threatens the structural support of the skeletal system. Osteoporosis, stress-risers, and the open-section effect result in pain, immobilization, and fractures. The establishment of more clear-cut indications for prophylactic fixation will lessen the morbidity associated with a pathologic fracture. PMID- 1589349 TI - Pathologic fractures of the humerus. AB - Pathologic fractures of the humerus create serious management problems. Impending fractures often can be anticipated. Fixation of impending or established fractures may provide significant benefits: comfort, improved functional ability, and facilitation of nursing care. PMID- 1589350 TI - Pathologic fractures of the acetabulum and the pelvis. AB - Metastatic involvement of the pelvis, and in particular the acetabulum, is a common finding among patients with metastatic osseous disease. With involvement of the joint surfaces, specifically the hip and sacroiliac joints, marked compromise of function can occur. With advances in imaging and the evolution of surgical reconstructive alternatives, most of these patients can be rendered pain free and functional by transferring weight distribution onto more stable elements of the hemipelvis. Reconstruction must be feasible and in the best interests of the patient. The decision to proceed represents a collective opinion of the patient, oncologist, and surgeon. PMID- 1589351 TI - Evaluation, prognosis, and medical treatment considerations of metastatic bone tumors. AB - Metastatic cancer can cause severe pain and disability. Metastases can occur in any bone, but usually are located in the axial or proximal appendicular skeleton. The most frequently encountered primary tumors that spread to bone are those of the prostate, breast, kidney, lung, and thyroid. When the origin of the primary cancer is known, skeletal metastases are more often from breast or prostate. When the primary site is unknown, the lung and kidney should be suspected as sites of origin. The nonoperative management of skeletal metastases from multiple myeloma and from carcinomas of the prostate, breast, kidney, lung, and thyroid are discussed. PMID- 1589352 TI - General perspectives, pathogenesis, pathophysiology, and skeletal dysfunction. AB - A better understanding of the pathogenesis and pathophysiology of the metastatic process is leading to improvements in diagnosis and treatment. Evaluation of specific areas of disorder of skeletal function, including hematopoiesis, mineral metabolism, and structural support, is important. Continued developments are necessary to minimize or prevent effects on the skeleton related to the metastatic process. PMID- 1589353 TI - Metastatic disease of the spine. AB - Advances in imaging studies and techniques of spinal stabilization permit improved surgical treatment of patients with metastatic disease of the spine. Preoperative evaluation, selection of patients for operative management, and results of published clinical series are reviewed. Surgical approaches for optimal tumor excision, neural decompression, and spinal stabilization are discussed. PMID- 1589354 TI - Metastatic disease of the femur. AB - Metastatic involvement of the femur is a common clinical problem and accounts for the third highest incidence after the spine and pelvis. These patients are confronted with the possibility of losing the ability to ambulate during their remaining months. However, with improved prosthetic implants and internal fixation devices, most patients can resume their previous activities after operative treatment of their femoral fractures. PMID- 1589355 TI - Overdesign of external fixation systems. AB - This article reviews 850 cases of open fractures of the extremities caused by high velocity missiles and shell fragments, and treated by two varieties of external fixation devices. If a protocol for grading the severity of injury is followed, the results encourage avoiding sophisticated, expensive, and overdesigned external fixation systems. PMID- 1589356 TI - Pathologic spinal fractures. PMID- 1589357 TI - On the dose of therapeutic exercise. PMID- 1589358 TI - Malignant melanoma metastatic to bone. PMID- 1589359 TI - Answer please. Eosinophilic granuloma. PMID- 1589360 TI - Government medicine. A bad dream come true? PMID- 1589361 TI - Pressure sores. How to prevent and treat them. AB - The consequences of immobility among hospitalized and bedridden patients, especially the elderly, can be devastating if pressure sores develop. Such sores are not only painful for the patient and expensive to manage, but they are potentially life-threatening. What can be done to prevent them? Which patients are most vulnerable? The authors address these questions and discuss treatment options. PMID- 1589362 TI - Understanding circulatory shock. Is it hypovolemic, cardiogenic, or vasogenic? AB - Circulatory shock comprises a group of complex circulatory syndromes that result from a variety of conditions. It alters the function of most organ systems and has very high mortality. Identification of the type of shock (hypovolemic, cardiogenic, vasogenic, or a combination) and optimal treatment are aided by hemodynamic monitoring, including determination of preload, cardiac output, and systemic vascular resistance. Experimental studies and isolation of bioactive substances have improved understanding of the mechanisms involved in shock. Restoration of intravascular volume, cardiac contractility, and vascular tone and control of the underlying septic process when applicable are the basis of current therapy. Close monitoring and support of the affected organ systems in an intensive care environment facilitate recovery. Encouraging results with new treatments indicate improved chances for a satisfactory outcome in patients with circulatory shock. PMID- 1589363 TI - Metastatic renal cell carcinoma presenting as a breast mass. AB - Metastasis of primary renal cell carcinoma to the breast, as in the patient described here, is rare. However, this case illustrates the importance of a high index of suspicion, further diagnostic evaluation based on results of routine tests, and use of appropriate imaging techniques in the workup of a patient with breast cancer. PMID- 1589364 TI - Looking for Mrs Brillo. PMID- 1589365 TI - Topflight choices in healthcare. PMID- 1589366 TI - Updates on Chlamydia. PMID- 1589367 TI - Is it Lyme disease? How to interpret results of laboratory testing. AB - Although laboratory testing is likely to have a greater role in diagnosis and monitoring of treatment of Lyme disease in the future, at present physicians must rely on a combination of history taking, clinical manifestations, and laboratory results. Unwarranted antibiotic therapy is to be avoided. Asymptomatic persons with positive serologic results who live in an endemic area present a challenge, and borderline serologic results in patients with manifestations of late Lyme disease are also troubling. All relevant clinical information must be considered before treatment is undertaken, until more specific and sensitive tests are available. PMID- 1589368 TI - Antibiotic treatment of Lyme disease. Current recommendations by stage and extent of infection. AB - Much has been learned about Lyme disease over the past several years, but much remains to be learned. Careful clinical observation has led to elucidation of the natural history of this disease, and further clinical observations are needed to unravel the remaining areas of uncertainty. It is by no means clear that all the symptoms attributed to Lyme disease today actually represent true manifestations of Borrelia burgdorferi infection or that patients with well-documented Lyme disease whose symptoms do not respond to antibiotic therapy have persistent infection. Immunologically mediated mechanisms may be responsible for the chronic disease manifestations that seem so resistant to antibiotics. Uncovering answers to these questions requires the close collaboration of astute practicing physicians and biomedical scientists working together for their patients' benefit. PMID- 1589369 TI - Special concerns in Lyme disease. Seropositivity with vague symptoms and development of fibrositis. AB - Fear of Lyme disease may be as powerful as the disease itself. Patients may insist on being tested for infection although little evidence of it exists, and a positive result in the face of vague symptoms can add to the problem. Physicians should explain to these patients the differences in "background" seropositivity in various geographic locations and the drawbacks of instituting unnecessary treatment. Fibrositis may evolve over time after Lyme disease infection. Many factors may trigger this disorder, but some investigators propose that it is a result of musculoskeletal pain, sleep disturbance, and anxiety over the disease. PMID- 1589370 TI - Pulmonary embolism. Clinical decision making to increase diagnostic accuracy. AB - In this article, Drs Kerr and Yan describe four cases--two handled the wrong way and two the right way--to help you frame a set of criteria that will work for you in suspecting, testing for, diagnosing, and treating pulmonary embolism in ambulatory patients. In addition, Dr Kerr uses his legal expertise to provide suggestions on avoiding liability resulting from inadequate documentation. PMID- 1589371 TI - Chronic liver disease. The scope of causes and treatments. AB - Evaluation of chronic liver disease begins with a carefully taken history, thorough physical examination, and standard laboratory tests. Often, however, other studies are required, such as a viral hepatitis panel, serologic tests for autoimmune markers, tests for antimitochondrial antibodies, measurement of serum iron and ceruloplasmin levels, liver biopsy, and imaging studies of the extra hepatic bile ducts. Medical treatment of chronic active hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis remains unsatisfactory. Early treatment of hemochromatosis and Wilson's disease can prevent cirrhosis and liver failure. Liver transplantation is now a viable procedure for patients with end-stage chronic liver disease. PMID- 1589372 TI - Panic disorder. Recognizing and managing the 'real thing'. AB - Panic disorder is a severe anxiety disease frequently encountered in primary care. Although it is associated with potentially serious medical and psychiatric complications and is often difficult to diagnose, the condition is highly treatable. Initial pharmacotherapy may include alprazolam (Xanax), imipramine hydrochloride (Janimine, Tofranil), or phenelzine (Nardil). Correct diagnosis and treatment can alleviate much suffering and expense and promote both mental and physical health. PMID- 1589374 TI - Raised blood urea in the elderly: a clinical and pathological study. AB - We have attempted to define a normal range for blood urea and creatinine for elderly inpatients and to determine the relative importance of pre-renal, renal and post-renal pathology in those with renal impairment. A total of 118 admissions to an acute geriatric unit and 67 separate post mortems in patients over 67 years of age were studied prospectively. Up to 123 items of data were coded and analysed including blood urea and creatinine, clinical or pathological changes associated with renal disease, clinical outcome and post mortem findings. We determined our own 'normal' hospital ranges for urea (1.4-13.2 mmol/l) and creatinine (48-141 mumol/l) from plasma values in 76 patients with no evidence of renal impairment, either on admission or in the past. Using these values 41% of post mortem cases and 25% of clinical admissions had a raised blood urea. Pre renal conditions such as cardiac failure, dehydration and gastrointestinal haemorrhage, either alone or in combination, were present in 56% of these patients. Urea and creatinine values were substantially higher in patients who died in hospital as opposed to those who were discharged or transferred. Creatinine values were greater in those with intrinsic renal disease or post renal obstruction as compared to patients with pre-renal causes of renal impairment. Patients with histological evidence of extensive glomerulosclerosis or nephrosclerosis had higher urea and creatinine levels than those with only minor ageing changes. PMID- 1589373 TI - Respiratory diseases. PMID- 1589375 TI - Hypertension in aortic valve disease and its response to valve replacement. AB - We have investigated the prevalence of hypertension and the response of blood pressure to operation in 87 patients with lone aortic valve disease who underwent aortic valve replacement. In patients with aortic stenosis alone 26% were hypertensive pre-operatively (age and sex adjusted blood pressure greater than 160 systolic and or greater than 95 mmHg diastolic) and 24% were hypertensive post-operatively. In those with aortic regurgitation alone, hypertension was present in 65% before and 57% after valve replacement using the same criterion. For combined stenosis and regurgitation, the prevalence was 54% and 62%, respectively. The post-operative increase in systolic pressure in patients with aortic stenosis occurred mainly in those with a history of left ventricular failure. In those with aortic regurgitation or combined stenosis with regurgitation, diastolic pressure rose after valve replacement resulting in a prevalence of diastolic hypertension of 44% and 35%, respectively. Blood pressure changes were not predicted by the type of valve inserted nor its size. Our data show that despite severe symptomatic aortic valve disease, systolic hypertension was common in aortic stenosis and diastolic hypertension was found in aortic regurgitation. This underlines the importance of blood pressure monitoring in patients following aortic valve replacement. PMID- 1589376 TI - Glomerulonephritis associated with antibodies to neutrophil cytoplasm and glomerular basement membrane. AB - The prognosis for recovery of renal function of oligoanuric patients with anti glomerular basement membrane disease is generally regarded as poor. Five patients are reported with dialysis-dependent renal failure in whom antibodies were present simultaneously both to neutrophil cytoplasm and glomerular basement membrane all of whom responded, at least initially, to immunosuppressive therapy and plasma exchange. Two of the 5 remain in clinical and immunological remission at 25 and 51 months of follow-up. We suggest that reversal of dialysis-dependent renal failure may be possible in some patients who display this dual antibody positivity. PMID- 1589377 TI - Adult metachromatic leukodystrophy with an unusual relapsing-remitting course. AB - A 46 year old woman had a relapsing-remitting course of hemiparesis, disorientation, paraparesis and seizures, followed by progressive dementia, spasticity and ataxia. Computed tomography at onset showed a parietotemporal hypodense area with diffuse mottled enhancement obliterating the lateral ventricle. Subsequent scans demonstrated symmetric periventricular non-enhancing hypodensities, progressive ventricular enlargement and atrophy. Adult metachromatic leukodystrophy was diagnosed on the basis of low leukocyte arylsulphatase A level and metachromatic material accumulation at neural nerve biopsy. PMID- 1589378 TI - Hypertension-renal ectopia, adrenal mass. PMID- 1589379 TI - Recovery of adrenocortical function following treatment of tuberculous Addison's disease. AB - We report two cases of Addison's disease occurring in association with proven Mycobacterium tuberculosis infection. Both were treated with modern chemotherapeutic agents and were shown to have developed normal adrenal cortical function after several years. We suggest that adrenal function should be tested after modern anti-tuberculous therapy of this disease. PMID- 1589381 TI - Systemic calciphylaxis presenting as a painful, proximal myopathy. AB - A renal transplant patient who presented with a painful, proximal myopathy due to systemic calciphylaxis is described. The myopathy preceded the characteristic skin and soft tissue necrosis. Systemic calciphylaxis should be considered in a dialysis or a renal transplant patient presenting with a painful proximal myopathy even in the absence of necrotic skin lesions. PMID- 1589380 TI - Glomerulonephritis in sarcoidosis: causal relationship unproven. AB - Two patients with sarcoidosis and glomerular mesangial proliferative lesions are described. Although a causative relationship between sarcoidosis and glomerulonephritis has been suggested, critical review of the literature fails to confirm this. PMID- 1589382 TI - Adult-onset mitochondrial myopathy. AB - Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. PMID- 1589383 TI - Localized scleroderma and hemiatrophy in association with antibodies to double stranded DNA. AB - Localized scleroderma involves primarily skin but also muscle, bone and synovium. Further associations and transitional forms have been reported. We report here two cases showing associations between localized scleroderma and vasculitis, mononeuritis multiplex, juvenile chronic arthritis and hemiatrophy. In particular our cases both possess antibodies to double-stranded DNA, a finding not previously reported. PMID- 1589385 TI - Femoral hernia appendix causing small intestinal obstruction. AB - An 88 year old woman presented with a painful, irreducible right femoral hernia and small intestinal obstruction. At laparotomy, some distal small intestine was found to have twisted around an uninflamed appendix which was acting as a 'band', with its tip fixed in the femoral hernia sac. Although the association between the appendix and femoral hernia is well recognized, the production of small intestinal obstruction by this particular mechanism has not been previously reported. PMID- 1589384 TI - Androgen-producing bilateral large cortical adrenal adenomas associated with polycystic ovaries in a young female. AB - An association of bilateral large adrenocortical androgen-producing adenomas with polycystic ovaries in a young female is presented. She developed mild hirsutism and secondary amenorrhoea at the age of 17, and was treated for 3 years with an anti-androgen (cyproterone acetate) and ethinyloestradiol. Routine follow-up at the age of 21 showed bilateral large adrenal tumours and polycystic ovaries, together with high serum testosterone and dehydroepiandrosterone sulphate values. Bilateral adrenalectomy was performed, which resulted in lowering of the elevated androgens, and large bilateral adrenocortical adenomas were confirmed histologically. Contrary to expectations, the polycystic appearance of the ovaries persisted after adrenalectomy. This case supports the possible role of adrenal androgens in the pathogenesis of polycystic ovaries as well as the possibility of the persistence of polycystic ovaries without adrenal androgens once they have developed. PMID- 1589386 TI - Testotoxicosis: gonadotrophin-independent male sexual precocity. AB - In this era of rapidly developing investigational tools and pharmacology, the pathophysiology of precocious puberty is becoming well defined. What was previously thought to be a form of gonadotrophin releasing hormone (GNRH) dependent central precocious puberty is now classified as GNRH-independent familial testotoxicosis. We present two such cases and review the clinical features, pathophysiology and treatment of testotoxicosis. PMID- 1589387 TI - Lymphoma presenting with Addison's disease. PMID- 1589388 TI - Herpes simplex encephalitis without CSF leucocytosis. PMID- 1589389 TI - Cerebellar ataxia due to hyponatremia. PMID- 1589390 TI - Spontaneous flail chest in multiple myeloma. PMID- 1589392 TI - Composite poly(vinyl alcohol) beads for controlled drug delivery. AB - A new method of preparing composite poly(vinyl alcohol) (PVA) beads with a double layer structure has been developed, which involves a stepwise saponification of suspension polymerized poly(vinyl acetate) (PVAc) beads and subsequent stepwise cross-linking of the PVA core and shell with glutaraldehyde. This process results in PVA beads with thin, highly cross-linked outer shells and lightly cross-linked inner cores of different degrees of cross-linking. In addition to structural characterization of the polymer based on equilibrium swelling measurements, the kinetics of water swelling and drug release from these beads were studied at 37 degrees C using acetaminophen and proxyphylline as model drugs. The results show that the outer shell functions as a rate-controlling membrane upon increasing its cross-linking ratio, X, above 0.47. This aspect is reflected in the observed diffusional time lags and constant-rate regions during swelling and drug release. Based on observed time lags, the diffusion coefficient of water through the outer PVA shell with a high cross-linking ratio of X = 0.5 is estimated to be at least six times higher than that of acetaminophen and proxyphylline. In addition, drug diffusion coefficients in the lightly cross-linked PVA core appear to be at least 10 times larger than that in the highly cross-linked outer shell. At lower shell cross-linking ratios (X less than 0.4), the diffusional time lags appear to be absent and the diffusion profiles are apparently first-order (Fickian) in nature. PMID- 1589391 TI - Drug metabolism in the nasal mucosa. AB - Nasal delivery is a potential alternative for systemic availability of drugs restricted to intravenous administration, such as peptide and protein drugs. Although nasal delivery avoids the hepatic first-pass effect, the enzymatic barrier of the nasal mucosa creates a pseudo-first-pass effect. The xenobiotic metabolic activity in the nasal epithelium has been investigated in several species including humans. The Phase I, cytochrome P-450 enzymes have been studied extensively for their toxicological significance, since these enzymes metabolize inhaled pollutants into reactive metabolites which may induce nasal tumors. The cytochrome P-450 activity in the olfactory region of the nasal epithelium is higher even than in the liver, mainly because of a three- to fourfold higher NADPH-cytochrome P-450 reductase content. Phase II activity has also been found in the nasal epithelium. The delivery of peptides and proteins has been hindered by the peptidase and protease activity in the nasal mucosa. The predominant enzyme appears to be aminopeptidase among other exopeptidases and endopeptidases. The absorption of peptide drugs can be improved by using aminoboronic acid derivatives, amastatin, and other enzyme inhibitors as absorption enhancers. It is possible that some of the surfactants, e.g., bile salts, increase absorption by inhibiting the proteolytic enzymes. Thus, in addition to the permeation barriers, there also exists an enzymatic barrier to nasal drug delivery, which is created by metabolic enzymes in the nasal epithelium. PMID- 1589393 TI - A sensitive and specific procedure for quantitation of ADR-529 in biological fluids by high-performance liquid chromatography (HPLC) with column switching and amperometric detection. AB - An HPLC method using electrochemical detection (ED) has been validated for the determination of ADR-529 in plasma and urine using ICRF-192 as an internal standard (IS). Prior to storage and quantitation, both plasma and urine samples require acid stabilization. Acidified plasma samples were prepared for HPLC using a two column solid-phase extraction (SPE). An aliquot of buffered plasma (i.e., pH 6-7) was first deproteinated and desalted on a C-18 SPE column. The analytes were then eluted onto a C-8 SPE column where retention and selective cleanup were achieved in the cation-exchange mode via silanol interactions. Acidified urine samples were diluted in acetonitrile prior to injection. The HPLC system for plasma and urine samples employed two narrow-bore silica columns used in the weak cation-exchange mode and separated by a switching valve. To prohibit late-eluting peaks from passivating the glassy carbon working electrode, a heart-cut containing ADR-529 and the IS was vented from the first silica column to the second using an automated switching valve. Amperometric detection at an oxidation potential of +1050 mV vs a Ag/AgNO3 reference electrode was used. Linearity was validated between 5 and 500 ng/ml in plasma and between 2 and 100 micrograms/ml in urine. Imprecision and percentage bias were typically less than 10% for both plasma and urine controls throughout their respective dynamic ranges. The absolute recoveries for ADR-529 and the IS from plasma were greater than 95%. This method is being successfully applied to the pharmacokinetic/dynamic evaluation of ADR-529 in animals and humans. PMID- 1589394 TI - Evaluation of the physical stability of freeze-dried sucrose-containing formulations by differential scanning calorimetry. AB - Freeze-dried samples of sucrose with buffer salts, amino acids, or dextran have been analyzed with differential scanning calorimetry (DSC) to evaluate the use of DSC thermograms in predicting the physical storage stability. The glass transition temperature, Tg, of the amorphous cake, crystallization, and melting of sucrose are observed with DSC. Tg appeared to be an important characteristic of the physical stability of the amorphous freeze-dried cake. A storage temperature above Tg results in collapse or shrinkage of the cake, which for a sucrose-based formulation, may be accompanied by crystallization of the sucrose. The Tg of the amorphous sucrose is influenced by other components present in the cake. Dextran-40 raised Tg, while the addition of glycine to the formulation lowered Tg. The residual moisture content strongly influences Tg, since water acts as a plasticizer of the system; the higher the moisture content, the lower the Tg and the less physically stable the freeze-dried cake. Crystallization of amorphous sucrose is shown to be inhibited by high molecular weight components or ionic compounds. DSC analysis of freeze-dried cakes proved to be a powerful tool in formulation studies. PMID- 1589395 TI - Analysis of hydroxyurea in capsules and aqueous solution and stability study with capillary gas chromatography and thermionic (N-P) specific detection. AB - A method for the analysis of hydroxyurea (HU) in solutions, powder, or capsules by use of capillary gas chromatography with N-P thermionic specific detection is described. Upon injection of an HU solution in a methanol and acetone mixture, the drug formed pyridine which was well separated from the internal standard (thiotepa) on a 30-m fused-silica, SE-30 capillary column with temperature programming. The peak height ratio versus concentration standard curves were linear with correlation coefficient ranging between 0.9942 and 0.9993. The coefficients of variation at 5, 25, and 50 micrograms/L were 7.2, 5.7, and 5.5%, respectively. Hydroxyurea was extracted from powder or capsule formulations with a mixture of methanol and acetone (50:50, v:v), and the percentage found of the label claim for 10 capsules ranged between 96.7 and 104.9 (mean = 100.1; CV = 2.7%). Further, this assay was used to examine the stability of hydroxyurea in aqueous solutions at 4, 23, and 45 degrees C, and the apparent first-order rate constants observed at these temperatures were 0.06407, 0.08113, and 0.1293 day-1, respectively; the activation energy was 3011 cal.K-1.mol-1. PMID- 1589396 TI - Validation of a column-switching high-performance liquid chromatographic (HPLC) method for determination of ML-1035 and its five metabolites in plasma. AB - A fully automated column-switching HPLC procedure has been developed and validated for quantitation of ML-1035 and its five metabolites in plasma employing direct injection. Plasma samples were injected onto a CN extraction column (4 x 4.6 mm, 5 microns) for micellar cleanup with 0.5% sodium dodecyl sulfate (SDS) in 50 mM phosphate. The proteinaceous components were solubilized and flushed out. The extracted compounds were then eluted by forward flush onto a C8 analytical column (150 x 4.6 mm, 5 microns) for further analysis using fluorescence detection (excitation, 308 nm; emission, 350 nm). After the subsequent washing and reequilibration with a sequence of three solvent mixtures, the extraction column was ready for the next injection. The limit of quantitation for all compounds of interest was about 10 to 15 ng/ml using 100 microliters of plasma. Excellent precision, accuracy, and linearity were obtained for all compounds over a range of 10 to 1500 ng/ml. The practicality of the HPLC method was also validated with plasma samples from dogs receiving ML-1035. Longevity for both extraction and analytical columns is excellent. Micellar cleanup coupled with the column-switching technique is a promising HPLC procedure when using direct injection of biological fluids. PMID- 1589397 TI - Surface characterization of activated charcoal by X-ray photoelectron spectroscopy (XPS): correlation with phenobarbital adsorption data. AB - X-ray photoelectron spectroscopy (XPS) was used to identify the functional states of carbon existing on the surfaces of various activated charcoals. The relative percentages of carbon, oxygen, and detectable trace elements comprising the activated charcoal surfaces were determined. Analysis of the carbon core-electron binding energy region revealed the existence of one hydrocarbon state (C-H, C-C are indistinguishable) and three oxygen-containing functional states. These states were hydroxyls or ethers (C-O), carbonyls (C = O), and carboxylic acids or esters (O-C = O). The C-O functional state contributed approximately 60-70% to the total percentage of oxygen-containing states. A very good correlation existed between the apparent areas occupied on the adsorbent surface per phenobarbital molecule and the relative percentages of the C-O functional state. Previously reported heat of displacement results for phenobarbital adsorption are now explained since the C-O state appears to be the primary site involved in the binding of phenobarbital by the activated charcoals. PMID- 1589398 TI - Kinetics of degradation of levothyroxine in aqueous solution and in solid state. AB - The kinetics of the deiodination of levothyroxine in aqueous solution were studied over the pH range 1 to 12. Temperature dependence of the reaction was also studied. The log k - pH profile indicated that the kinetics of deiodination include proton attack on the anion and dianion in acidic solution and water attack on the anion and dianion in alkaline solution. A possible mechanism of the deiodination was discussed. The solid-state stability of levothyroxine sodium was studied at elevated temperatures; and the compound was found to undergo deamination on heating. The decomposition follows biphasic first-order kinetics, with the most rapid decomposition occurring at the beginning of heating. PMID- 1589399 TI - Kinetic study of the transformation from tetrahydrate to monohydrate of a new antiallergic, sodium 5-(4-oxo-phenoxy-4H-quinolizine-3-carboxamide)-tetrazolate. AB - Two hydrates (tetrahydrate, I, and monohydrate, II) of a new antiallergic, sodium 5-(4-oxo-phenoxy-4H-quinolizine-3-carboxamide)-tetrazolate (FR71021), were prepared and characterized by means of infrared spectrometry, thermal analysis, and power X-ray diffraction spectrometry. While I was confirmed to dehydrate readily resulting in an anhydrate form (noncrystalline form) below its critical relative humidity for dehydration, I was also transformed into II under humid conditions. The transformation kinetics from I to II were investigated under varying temperature and humidity conditions by a powder X-ray diffraction technique. The transformation mechanism followed a zero-order reaction, and the apparent transformation rate constant (k) could be described as a function of water vapor pressure (P), temperature (T), and the interaction orders between water vapor pressure and the samples (s): k = A.exp(-Ea/RT).Ps, where Ea is the activation energy and R is the gas constant. PMID- 1589400 TI - Bisacylphosphonates inhibit hydroxyapatite formation and dissolution in vitro and dystrophic calcification in vivo. AB - Some geminal bisphosphonates are used clinically for a number of important bone/calcium related diseases; however, side effects and lack of selectivity impede their wide use. This work reports the synthesis and evaluation of bisacylphosphonates (e.g., adipoyl- and suberoylbisphosphonate). These compounds were found to inhibit significantly hydroxyapatite formation and dissolution in vitro and the calcification of bioprosthetic tissue implanted subdermally in rats. These are the first instances of nongeminal bisphosphonates [P-(C)n-P, n greater than or equal to 2] that have been reported to be active in calcium related disorders. The reported bisacylphosphonates possess apparent lower toxicity, and their calcium complexes/salts have improved solubility properties. Therefore, they are of potential importance for clinical applications. PMID- 1589401 TI - Poly(L-lactic acid) microspheres containing neutron-activatable holmium-165: a study of the physical characteristics of microspheres before and after irradiation in a nuclear reactor. AB - The solvent evaporation technique was employed to prepare poly(L-lactic acid) (PLA) microspheres with 165Ho acetylacetonate (Ho-AcAc). Particle size, percentage Ho-165, percent residual solvent, and retentive ability of the spheres were found to be strongly affected by preparatory conditions. Differential scanning calorimetry (DSC) thermograms suggested that the Ho-AcAc existed in the PLA matrix as a molecular dispersion. High neutron flux irradiations of the PLA spheres in a nuclear reactor produced Ho-166, a therapeutic radionuclide that emits high-energy negatrons (Emax = 1.84 MeV; half-life = 26.9 hr). The gamma radiation dose (53-75 Mrad) from the core of the reactor provided an overkill of all bioburdens in the PLA spheres. Gel permeation chromatography (GPC) analysis showed that these irradiations caused a reduction in PLA molecular weight. Infrared spectra, 13C NMR spectra, 1H NMR spectra, and DSC thermograms further confirmed the presence of lower molecular weight PLA but proved the overall maintenance of PLA structure. PMID- 1589402 TI - Potential use of microdialysis in pharmacokinetics: a protein binding study. PMID- 1589403 TI - Iceberg formation and the resulting effects on rates of hydrolysis of aspirin. PMID- 1589404 TI - Estimation of permanence time, exit time, dilution factor, and steady-state volume of distribution. AB - General solutions for exist time, permanence time, dilution factor, and volume of distribution at steady state are derived for compartmental and noncompartmental systems. These derivations require that the systems are linear and state determined. Unique values for these parameters cannot be determined when the site of elimination is not known; in this case the parameters can be defined by a range. Interpretation of this range and its significance and use in clinical situations are illustrated with two examples. PMID- 1589405 TI - The influence of polymer glass transition temperature and molecular weight on drug release from tablets containing poly(DL-lactic acid). AB - Five molecular weight grades of poly(DL-lactic acid) were characterized using gel permeation chromatography, differential scanning calorimetry, and viscometry to determine the effect of molecular weight on the glass transition temperature and the intrinsic viscosity. In addition, dynamic mechanical thermal analysis was used to assess the dynamic storage modulus and the damping factor of the polymer samples by detecting motional and structural transitions over a wide temperature range. Significant relationships were found between the molecular weight and these polymer properties. The five grades of poly(DL-lactic acid) were also incorporated as binders into matrix tablet formulations containing the model drug theophylline and microcrystalline cellulose. Dissolution studies showed significant correlations between the properties of the polymer and the matrix release profiles of the tablets. The release of theophylline slowed down progressively as the polymer molecular weight increased. The differences in release became less significant and reached a limiting asymptotic value as the molecular weight increased to 138,000. Further, tablet index testing was utilized to determine the compaction properties of the polymer granulations. Although there was no correlation with the molecular weight of PLA, brittle fracture index testing indicated very low brittleness for all granulations tested. However, bonding index determinations correlated very well with both the physical mechanical properties of the polymer and drug release profiles. PMID- 1589406 TI - Lyophilized formulations of recombinant tumor necrosis factor. AB - Recombinant tumor necrosis factor-alpha (TNF), an investigational biological response modifier, is a protein and is susceptible to particulate generation during handling in dilute aqueous solutions. TNF is prone to formation of nonreducible dimers and oligomers during formulation, lyophilization, and storage. The effect of various parameters, such as the pH, protein concentration, and nature of excipients present during lyophilization, on the formation of nonreducible dimers and oligomers was investigated. The results of these studies indicate that these parameters can significantly alter the rate of this reaction. Inclusion of an amorphous buffer and an appropriate amount of a crystallizing sugar (mannitol) combined with a suitable quantity of an amorphous protectant (dextran, sucrose, trehalose, or 2-hydroxypropyl-beta-cyclodextrin) was shown to reduce the formation of these dimeric and oligomeric species during lyophilization. Representative lyophilized formulations of TNF based on selected amorphous excipients were found to be fully bioactive and stable over 9 months. PMID- 1589407 TI - Controlled protein release from polyethyleneimine-coated poly(L-lactic acid)/pluronic blend matrices. AB - Protein release from degradable polymer matrices, composed of poly(L-lactic acid) and its blends with Pluronic surfactant, was investigated with and without the aqueous coating of an adsorptive water-soluble polymer, polyethyleneimine (PEI). PEI is a highly branched cationic polymer containing primary, secondary, and tertiary amino groups in its backbone. The treatment of PEI for PLA/Pluronic blend films exhibited a remarkable decrease in the "burst" release of protein at an initial stage and a significant extension in the protein release period. Protein release profiles could be controlled by varying PEI treatment time and its concentration. Our results suggest that PEI diffuses into the polymer matrices and crosslinks protein molecules by ionic interactions. Such a PEI protein network near the surface region of matrix may act as a diffusional barrier for further release of protein molecules. PMID- 1589408 TI - Localization of epidermal growth factor (EGF) binding sites on antiluminal plasma membrane of rat kidney: autoradiographic study using nonfiltering perfused rat kidney. AB - We previously demonstrated that the specific binding of EGF to the antiluminal plasma membrane was a prerequisite step for the renal uptake of EGF. In the present study, the localization of 125I-EGF binding sites on the antiluminal plasma membrane was investigated by tissue sampling and X-ray autoradiography in the nonfiltering kidney. The binding of 125I-EGF was recognized over the whole kidney and was highest in the inner medulla followed by the cortex and outer medulla. The binding of 125I-EGF in the nonfiltering kidney was completely inhibited in the presence of 20 nM unlabeled EGF, suggesting specific binding of 125I-EGF to its receptor. Further, we used a histologic tissue staining method to confirm the location of the 125I-EGF binding sites. Binding of 125I-EGF was demonstrated on the proximal straight tubules (PST), cortical collecting ducts (CCD), inner medullary collecting ducts (IMCD), and thin limb of Henle in the inner medulla (IMTLH). We found that the binding of 125I-EGF was high in the IMTLH. In addition, we determined the grain density both on the cell surface membrane and in the intracellular space of the proximal straight tubules, where the grain density on the antiluminal plasma membrane was approximately 50% that in the intracellular space at 20 min after the start of 125I-EGF perfusion, suggesting the internalization of 125I-EGF from the antiluminal plasma membrane to the intracellular compartment. In conclusion, the binding sites of 125I-EGF, which were accessible from the antiluminal side, were broadly distributed over the whole kidney and were most dense around the IMTLH. PMID- 1589409 TI - Feasibility of measuring the bioavailability of topical betamethasone dipropionate in commercial formulations using drug content in skin and a skin blanching bioassay. AB - An in vivo technique has been developed which simultaneously compares a skin blanching bioassay with drug content in human stratum corneum following topical application of four 0.05% betamethasone dipropionate formulations. Bioavailability of drug from commercial cream and ointment formulations was assessed by quantification of drug content in tape-stripped stratum corneum and skin blanching in the treated skin site under occluded conditions. Tape-stripping removed stratum corneum to a varying degree between individuals but was consistent (35%) within an individual with all formulations, day to day. A correlation (r = 0.9935) between the amount of drug in the treated stratum corneum normalized for surface area and the corresponding skin blanching score was observed with four 0.05% betamethasone dipropionate formulations. Increasing the amount of drug in the tape-stripped stratum corneum correlated with an increased skin blanching score. Ointment formulations delivered more drug to the skin and produced greater blanching scores than the cream formulations. Topical corticosteroid content in the treated skin site can therefore be quantified and correlates well with the resulting pharmacodynamic activity. PMID- 1589410 TI - Tolerability and absorption enhancement of intranasally administered octreotide by sodium taurodihydrofusidate in healthy subjects. AB - Nasal sprays containing different concentrations of the somatostatin analogue octreotide and sodium tauro-24,25-dihydrofusidate (STDHF) as an absorption promoter were evaluated in two consecutive pharmacokinetic studies in healthy volunteers to characterize their bioavailability and local tolerability. The concentrations of STDHF were selected on the basis of a phase diagram generated by a dynamic laser light-scattering technique to ensure that the mixture was above the critical micellar concentrations. Compared to a 50-micrograms subcutaneous injection, the nasal spray formulation without STDHF had a mean relative bioavailability of 17.9%. For nasal formulations containing 3 and 1.65% (w/v) of STDHF, the bioavailability increased to 29.0 and 25.7%, respectively. The enhancement of nasal absorption was dependent on the STDHF concentrations as shown by decreasing the amounts to 1.2 and 0.8% (w/v) for tolerability reasons; the bioavailability was reduced to 15.3 and 20.5% in these cases, respectively. The local tolerability of all STDHF-containing sprays was poor, leading to stinging sensations and lacrimation. The poor local tolerability of the octreotide nasal spray containing different concentrations of STDHF required for effective nasal absorption enhancement appears to be impractical for further clinical development. These findings clearly stress the necessity to investigate tolerability and safety issues of new drug delivery systems in early developmental phases. PMID- 1589411 TI - Dissolution of ionizable drugs into unbuffered solution: a comprehensive model for mass transport and reaction in the rotating disk geometry. AB - A model has been developed to describe the mass transport and reaction of ionizable compounds where mass transfer is caused by convection and diffusion from a rotating disk. Dissolution rates of benzoic acid, 2-naphthoic acid, and indomethacin in aqueous solutions of high ionic strength (I = 0.5 with potassium chloride) at 25 degrees C were investigated. The model includes the effects of diffusion, convection, and simultaneous acid/base reaction at all points in the region adjacent to the dissolving solid. The solution of the transport equations is obtained numerically with an iterative algorithm which uses (a) closure of all material balances and (b) equilibria at the solid/liquid surface as constraints. The model solution yields both the flux of the dissolving acid and the concentration profile of each component. Reduced values of all reaction rate constants are used in the region adjacent to the dissolving surface to allow convergence of the computation. Although nonequilibrium concentration values are calculated, it is shown that the theoretical dissolution rate determined as the solution of the model is insensitive to the magnitude of the rate constants as their maximum useable values are approached. Comparisons of the model results with experimentally determined fluxes show close agreement and confirm that the transport mechanisms in the model formulation are consistent with the measured values. Further, the inclusion of convection allows accurate calculations without utilization of an arbitrary boundary layer thickness. Accurate dissolution rates can be determined using this technique under a wide range of conditions, except at low pH. PMID- 1589412 TI - A surface energy analysis of mucoadhesion: contact angle measurements on polycarbophil and pig intestinal mucosa in physiologically relevant fluids. AB - The possible role of surface energy thermodynamics in mucoadhesion was investigated with Polycarbophil and pig intestinal mucosa. In separate experiments, the surface energy parameters of the substrate (mucosa) and the adhesive (polymer film) were determined by contact angle measurements on captive air/octane bubbles in three physiologically relevant test fluids (isotonic saline, artificial gastric fluid, and artificial intestinal fluid). Whereas the swollen Polycarbophil films were relatively hydrophilic as indicated by small water contact angles (22, 23, and 16 degrees), the water contact angles measured on mucosal tissue were significantly larger (61, 48, and 57 degrees). Hence, mucus was found to possess an appreciable hydrophobicity. The measured adhesive performance (force of detachment) between Polycarbophil and pig small intestinal mucosa was highest in nonbuffered saline medium, intermediate in gastric fluid, and minimal in intestinal fluid. In agreement with this trend, the mismatch in surface polarities between substrate and adhesive, calculated from the contact angle data, increased in the same order. PMID- 1589413 TI - Buffer effects on swelling kinetics in polybasic gels. AB - The swelling kinetics of polybasic gels consisting of copolymers of methyl methacrylate and dimethylaminoethyl methacrylate are studied in solutions at various acidic pH values, with monoacidic derivatives of acetic acid added as buffers. The effects of solution pH, as well as buffer pKa and concentration, on swelling rate are assessed. Gel swelling rate shows a nearly linear dependence on the concentration of nonionized buffer in the solution, as determined by the Henderson-Hasselbach equation. This result is explained in terms of the increased availability of protons that are carried by the nonionized buffer to bare amines on the gel. In fact, the so-called pH sensitivity of these gels, under these conditions, can be attributed mainly to the effect of pH on the nonionized buffer concentration. A practical consequence is that these gels may not reliably mediate pH-sensitive swelling-controlled release in oral applications, since the levels of buffer acids in the stomach (where swelling and release are expected to occur) generally cannot be controlled. However, the gels may be useful as mediators of pH-triggered release when precise rate control is of secondary importance. PMID- 1589414 TI - Influence of formulation, receptor fluid, and occlusion, on in vitro drug release from topical dosage forms, using an automated flow-through diffusion cell. AB - An automated flow-through diffusion cell apparatus was used for comparing the release rates of a naphthoic acid derivative, CD 271, from different topical formulations. The influence of the following parameters on CD 271 release from the formulations was investigated: receptor fluid composition, occlusion, weight of tested formulation, and dosage form type. The amount of tested formulation was shown to have no significant effect on the apparent release constant and lag time for an anionic oil-in-water emulsion and an aqueous gel. Occlusion affected drug release from the different dosage forms. Thus, occlusion increased CD 271 pharmaceutical availability for a lotion and a hydroalcoholic gel containing 0.1% of solubilized drug. The release profile of CD 271 from the formulations was highly dependent on the receptor fluid composition. Drug release was dramatically enhanced with n-octanol as compared to an aqueous solution of surfactant. Using occlusive or nonocclusive procedures, CD 271 apparent release constant and lag time were found to be highly dependent on the type of tested formulation. The flow-through diffusion cell proposed in the present study allows an accurate comparison of drug release characteristics from prototype topical formulations and therefore represents a valuable tool for formulation research or quality control process. PMID- 1589415 TI - Self-emulsifying drug delivery systems: formulation and biopharmaceutic evaluation of an investigational lipophilic compound. AB - Self-emulsifying drug delivery systems (SEDDSs) represent a possible alternative to traditional oral formulations of lipophilic compounds. In the present study, a lipophilic compound, WIN 54954, was formulated in a medium chain triglyceride oil/nonionic surfactant mixture which exhibited self-emulsification under conditions of gentle agitation in an aqueous medium. The efficiency of emulsification was studied using a laser diffraction sizer to determine particle size distributions of the resultant emulsions. An optimized formulation which consisted of 25% (w/w) surfactant, 40% (w/w) oil, and 35% (w/w) WIN 54954 emulsified rapidly with gentle agitation in 0.1 N HCl (37 degrees C), producing dispersions with mean droplet diameters of less than 3 microns. The self emulsifying preparation was compared to a polyethylene glycol 600 (PEG 600) solution formulation by administering each as prefilled soft gelatin capsules to fasted beagle dogs in a parallel crossover study. Pharmacokinetic parameters were determined and the absolute bioavailability of the drug was calculated by comparison to an i.v. injection. The SEDDS improved the reproducibility of the plasma profile in terms of the maximum plasma concentration (Cmax) and the time to reach the maximum concentration (tmax). There was no significant difference in the absolute bioavailability of WIN 54954 from either the SEDDS or the PEG formulations. PMID- 1589416 TI - Complexation studies of cyclodextrins with tricyclic antidepressants using ion selective electrodes. AB - The complexation of six tricyclic antidepressant drugs [amitriptylin (AMN), nortriptylin (NRN), imipramin (IMN), doxepin (DXN), protriptylin (PTN), and maprotilin (MPN)] with alpha- and beta-cyclodextrins (CDs) using ion-selective electrodes (ISEs) as drug ion sensors is described. Binding parameters were calculated by nonlinear fitting of the model described by the Scatchard equation, to the experimental data of a titration of a CD solution with the ion of interest. One binding site (the CD cavity) was found in all cases with both CDs. The calculated association constants at 25 degrees C using CD concentrations in the range of 0.0100-0.0010 M, varied from 4.81 x 10(3) M-1 (MPN) to 23.9 x 10(3) M-1 (AMN) in the case of beta-CD and from 50 M-1 (DXN) to 123 M-1 (MPN) in the case of alpha-CD. The precision for the estimation of the binding parameters was 0.1-5.0% (within-run RSD%) and 8-10% (between-run RSD%; n = 3). The complexation of the drugs with beta-CD was also examined as a function of temperature in the range of 5-37 degrees C; it was found to decrease by increasing temperature. Van't Hoff analysis gave good correlations (r greater than or equal to 0.989) for all drug ions studied. The estimates of the thermodynamic parameters indicate that the formation of inclusion complexes is enthalpy driven. A compensation plot based on the thermodynamic parameters delta H and delta S resulted in a linear relationship, which is indicative of a common type of force involved in the complexation of drugs to beta-CD. PMID- 1589417 TI - Apparent non-mosaic trisomy 16 in chorionic villi: diagnostic dilemma or clinically significant finding? AB - A case is presented in which apparent non-mosaic trisomy 16 was found in chorionic villi (direct and culture) obtained from a patient undergoing first trimester prenatal diagnosis. The fetal karyotype subsequently was determined to be 46,XX by follow-up amniocentesis. Serial ultrasonographic examinations revealed placental sonolucencies and intrauterine growth retardation. At 37 weeks, a small-for-gestational-age female was delivered by Caesarean section for fetal distress. Postnatal cytogenetic studies revealed a normal female karyotype in cord blood and mosaic trisomy 16 in placental tissues. These findings suggest that in cases where aneuploidy is confined to placental tissues, it may have biological significance, as evidenced by the apparent placental dysfunction and poor fetal growth in this case. PMID- 1589418 TI - Prenatal diagnosis of Pompe's disease (type II glycogenosis) in chorionic villus biopsy using maltose as a substrate. AB - Uncultured trophoblasts obtained from chorionic villus biopsy during the gestation period of 8-12 weeks were assayed for alpha-glucosidase activity using maltose as the substrate. Only one major form of maltase activity with a pH optimum at 4.0 was demonstrated. Using this method, we performed prenatal diagnosis on three pregnancies at risk for the infantile form of type II glycogen storage disease. Two affected fetuses and one unaffected fetus were predicted and the diagnosis was subsequently confirmed. The maltose assay offered a direct, simple, and sensitive method for prenatal diagnosis of Pompe's disease in the first trimester. PMID- 1589419 TI - Prenatal sonography in trisomy 9. AB - Two cases of trisomy 9 are presented with the description of the prenatal sonographic findings prompting prenatal cytogenetics evaluation. The characteristic sonographic abnormalities included structural heart defects; limb, renal, and facial anomalies; and intrauterine growth retardation. The clinical course and cytogenetic and autopsy finding are described. PMID- 1589420 TI - Factors associated with multiple-pass procedures during chorionic villus sampling: a video analysis. AB - Multiple placental passes during chorionic villus sampling (CVS) increase the risk of fetal loss; however, specific factors that predispose to repeat aspiration have not been delineated. To identify anatomic and technical variables associated with multiple-pass procedures, a detailed review of 205 videotaped CVS procedures (single pass = 163; multiple pass = 42) was performed, blinded to pregnancy outcome. The route of sampling did not influence the need for multiple aspiration attempts (transabdominal--30/135; transcervical--12/70), nor was placental location alone discriminatory. However, the combination of a posterior placenta and uterine retroversion was observed more frequently in the multiple pass cohort (8/42 vs. 9/163; p less than 0.05). In transabdominal cases, suboptimal needle placement (e.g., perpendicular to the placental long axis) was more common in the initial aspiration of a multiple-pass procedure (21/30 vs. 38/105; p less than 0.01), while limited penetration of the catheter tip (e.g., just inside the placental edge) characterized a majority of multiple-pass cases in the transcervical subset (7/12 vs. 3/58; p less than 0.0001). A case-control cohort was constructed to evaluate the impact of these technical variables on sampling efficacy, independent of the influence of uterine position and placental site. In that analysis, suboptimal location and/or orientation of the sampling device remained characteristic of multiple-pass cases. We conclude that further reduction in the frequency of multiple-pass procedures might be achieved by consistent placement of the device tip in the central placental mass. Unlike amniocentesis, where any point of amnion entry will suffice, this technical nuance should be emphasized with CVS to maximize the single-pass success rate. PMID- 1589421 TI - The psychosocial sequelae of a second-trimester termination of pregnancy for fetal abnormality. AB - A retrospective study to investigate the psychosocial sequelae of a second trimester termination of pregnancy (TOP) for fetal abnormality (FA) is described. After appropriate consent was obtained, 84 women and 68 spouses were visited 2 years after the event and asked to complete an extensive questionnaire. Most couples reported a state of emotional turmoil after the TOP. There were differences in the way couples coped with this confusion of feelings. After 2 years about 20 per cent of the women still complained of regular bouts of crying, sadness, and irritability. Husbands reported increased listlessness, loss of concentration, and irritability for up to 12 months after the TOP. In the same period, there was increased marital disharmony in which 12 per cent of the couples separated for a while and one couple obtained a divorce. These problems could be attributed to a lack of synchrony in the grieving process. Confusing and conflicting feelings led to social isolation and lack of communication. Difficulties in coming to terms with the fetal loss were not found to be linked to the type of fetal abnormality or religious beliefs but were related to parental immaturity, inability to communicate needs, a deep-rooted lack of self esteem before the pregnancy, lack of supporting relationships, and secondary infertility. Suggestions for improved management are given. PMID- 1589422 TI - Chorionic villus sampling and selective termination of a chromosomally abnormal fetus in a triplet pregnancy. AB - Transabdominal chorionic villus sampling (CVS) was performed on a patient with a triplet pregnancy. The karyotypes were as follows: 46,XX; 46,XY; and 46,XY/47,XXY. Selective termination was done on the affected fetus successfully by intrathoracic potassium chloride (KCl) injection. Amniocentesis which was performed at the same time confirmed the CVS results, showing the same mosaic findings. Following the procedure, the pregnancy proceeded uneventfully and two normal newborns were delivered at term. PMID- 1589423 TI - First-trimester ultrasonic diagnosis of twin reversed arterial perfusion sequence. AB - Twin reversed arterial perfusion (TRAP) syndrome sequence is a rare specific anomaly of twin gestation with fused placentae and umbilical anastomosis. This syndrome occurs once in very 35,000-48,000 births and has been described in the second trimester (23-29 weeks of gestation). We report on early sonographic diagnosis (10 and 12 weeks' gestation) of two cases of TRAP sequence, together with their umbilical cord Doppler studies. PMID- 1589424 TI - Transvaginal chorionic villus sampling using transabdominal ultrasound guidance. AB - Transvaginal chorionic villus sampling (CVS) using concurrent transabdominal ultrasound guidance was performed in six women who desired CVS but could not be offered transcervical or transabdominal approaches because of uterine position and placental location. Satisfactory amounts of chorionic villi were obtained in all six cases with no maternal discomfort, an occurrence that contrasts with our experience in transvaginal CVS using endovaginal ultrasound guidance. We believe that transvaginal CVS using concurrent transabdominal ultrasound guidance warrants consideration as an alternative technique for first-trimester CVS in selected patients. PMID- 1589425 TI - Isolation of Pneumocystis carinii cysts by flow cytometry. AB - Pneumocystis carinii cysts were separated as enriched populations from suspensions of lung homogenate obtained from infected rats containing all developmental stages of this organism. Isolation of cyst populations was achieved by incubating filtered lung homogenate with the fluorescent phospholipid analog 1 palmitoyl-2-C6-NBD-phosphatidylcholine. Whereas cysts did not fluorescence as a result of outer-wall restraint of lipid integration, trophozoites and young intermediate stages readily incorporated the fluorescently labeled lipid analog into their outer membrane. The two distinct labeling patterns displayed by cysts and other developmental phases of P. carinii constitute a novel, easy, and reproducible means of isolating cysts from infected lung homogenate by flow cytometry. PMID- 1589426 TI - Treatment of fish parasites. 9. Effects of a medicated food containing malachite green on Ichthyophthirius multifiliis Fouquet, 1876 (Hymenostomatida, Ciliophora) in ornamental fish. AB - For systemic therapy against trophozoites of the skin-inhabiting stage of Ichthyophthirius multifiliis in ornamental fish, the latter were fed medicated food flakes containing malachite green once daily for 1-11 days ad libitum. Naturally or artificially infected cardinal tetras (Paracheirodon axelrodi), blue gouramis (Trichogaster trichopterus), or clown loach (Botia macracantha) were used in the trials. The fish were maintained in aerated 12.5- or 60-1 aquaria at 23 degrees C. Ultrastructural investigations (scanning and transmission electron microscopy) revealed clear deleterious effects of malachite green on the parasitic stages. Following the initial application, the inner membrane of the mitochondria was destroyed. In fish fed for 2 days, aggregation of the mucocysts and polymerization the microtubules within the macronucleus occurred. Finally, the trophozoite's membrane was completely destroyed. In fish fed for 4 days, the medicated food killed all trophozoites of I. multifiliis. Sensitive ornamental fish (e.g., P. axelrodi) showed no adverse effects after they had been fed with only the medicated food flakes for 2 months. Therefore, the oral administration of malachite green using this newly developed medicated food considerably reduces the risk of toxic effects on the fish hosts, which are sometimes caused by malachite green following its application by immersion therapy. The feeding of flakes medicated with malachite green provides and easy-to-handle and highly effective treatment of I. multifiliis in ornamental fish. PMID- 1589428 TI - Loma camerounensis sp. nov. (Protozoa:Microsporida) a parasite of Oreochromis niloticus Linnaeus, 1757 (Teleost:Cichlidae) in fish-rearing ponds in Melen, Yaounde, Cameroon. AB - A new microsporidian, Loma camerounensis, was found in the Cichlidae Oreochromis niloticus from the Melen fish-rearing station in Yaounde, Cameroon. Xenomas were located in the gut from the oesophagus to the intestine, but preferentially in the duodenum. Dimensions of the fresh spores were 3.96 x 2.16 microns. The ultrastructural study indicated the following characteristics: parasite stages arranged in a random, unstratified manner in the xenoma; merogony by multiple fission; sporogonic stages isolated within a sporophorous vesicle containing several sporoblasts and polysporoblastic sporogony. Ultimately the spores appeared to be isolated in a single vesicle, but this was a secondary phenomenon induced by the intervention of tubules that resolved in partitions of the initial sporophorous vesicle. PMID- 1589427 TI - Rapid transport of the acidic phosphoproteins of Plasmodium berghei and P. chabaudi from the intraerythrocytic parasite to the host membrane using a miniaturized fractionation procedure. AB - A miniaturized procedure for the separation of the host erythrocyte membrane from malarial parasites based on saponin lysis and density-gradient centrifugation with Percoll is described. The procedure requires only 20-35 microliters packed infected erythrocytes, is simple to perform, needs no sophisticated equipment, and can be completed in less than 2 h. Analysis of the isolated erythrocyte membranes and parasites using marker enzymes and electron microscopy revealed that both the purity and the yield of these fractions were relatively high. Erythrocyte membrane proteins, including spectrin, ankyrin, and band 4.1, were not found on the parasitophorous vacuolar membrane, which remained associated with some but not all of the isolated parasites. Application of this method to pulse-chase experiments indicated that the acidic phosphoproteins of Plasmodium berghei and P. chabaudi were rapidly transported from the parasite to the erythrocyte membrane immediately after their synthesis. The rapid export of these acidic phosphoproteins from the parasite distinguishes them from other proteins exported by the malarial parasite. PMID- 1589429 TI - Ultrastructural aspects of Trypanosoma (Megatrypanum) freitasi in co-cultivation with mammalian cells. AB - Cultures of Trypanosoma (Megatrypanum) freitasi with L929 mouse fibroblasts at 27.5 degrees C were examined by scanning and transmission electron microscopy in an attempt to clarify the processes of colony formation by the epimastigotes and of their attachment to substrata. It was seen that the flagellates occupy intercellular spaces and do not associate with intact fibroblasts. As the trypanosome population increases, ever larger portions of the substratum are cleared of fibroblasts and occupied by conglomerates of epimastigote colonies consisting of about a dozen organisms that attach to the substratum by their anterior extremities and form pyramidal clusters. Attachment of the epimastigotes involves the flagellar membrane, which becomes extraordinarily enlarged and assumes various aspects of broad sheets, filaments and loops over the substratum or along the flagellum, which exhibits a shortened axoneme. Desmosome or hemidesmosome plaques are present when the attachment takes place between membranes or between the membrane and the substratum. PMID- 1589430 TI - Analysis by immunoblotting of Toxoplasma gondii exo-antigens and comparison with somatic antigens. AB - Two soluble Toxoplasma gondii antigen preparations were compared using the immunoblotting technique. The first preparation, which is commonly employed in ELISA tests, corresponds to a lytic extract of the parasite. The second known as exo-antigen, has yielded good results in cell immunity research and is obtained from Toxoplasma gondii culture supernatants. In both preparations, components exhibiting same molecular weight of 57-52 (doublet), 43, 38, 35, 30 and 20 kDa were revealed. In addition, two major 27- and 78-kDa components were detected in exo-antigens. The 30 kDa protein was intensely recognised by all sera, confirming the advantage of its use as an antigen in serological reactions. Exo-antigens could be employed as a soluble antigenic solution because they are easy to obtain, they display good antigenicity and their antigenic composition has been defined. Moreover their preparation does not require mouse inoculation. An evaluation of the enzyme-linked immunosorbent assays (ELISAs) involving these antigens has yet to be performed. PMID- 1589431 TI - Dose-dependent recovery of adult Acanthocheilonema viteae (Nematoda: Filarioidea) after single and trickle inoculations in jirds. AB - Increasing single doses of 5, 15, 30, 60 and 90 third-stage Acanthocheilonema viteae larvae per animal were inoculated into jirds. The adult worm load increased steadily, whereas the recovery rate decreased significantly, i.e. the correlation between dose and recovery was negative (rs, -0.90; n = 5; alpha, 0.05). The same inoculation doses were given as trickle inoculations of 5 L3 each (3 x 5, 6 x 5, 12 x 5, 18 x 5) at intervals of 2-6 days throughout the prepatency period. Irrespective of the number of repeated inoculations, a rather constant but low load of 7-10 worms/animal was reached. The recovery rate decreased drastically (rs, -1.0; n = 5). When trickle inoculations were carried out in animals exhibiting patient infections, the superinoculated larvae seemed to be destroyed almost completely; thus, a parasite-host equilibrium was guaranteed in all cases. The immunological background is discussed. PMID- 1589432 TI - Effect of carrageenan on the resistance of congenitally athymic nude and normal BALB/c mice to infective larvae of Brugia malayi. AB - Resistance of BALB/c mice to infective third-stage larvae (L3) of the human filarial parasite Brugia malayi is thymus-dependent, although the actual effector mechanisms that mediate larval killing are unknown. The present study examined the effect of carrageenan (CGN) on the mechanisms of resistance to B. malayi infection in heterozygous (nu/+) and nude (nu/nu) mice. Mice were treated with CGN at a single dose of 20 or 200 mg/kg and were inoculated intraperitoneally 1 day later with 100 L3. The results showed a dose-dependent increase in the numbers of L4 and L5 that were recovered from nu/+ and nu/nu mice. CGN treatment also enhanced the recovery of mature adult worms from nu/nu mice and appeared to abolish partially the dichotomy of resistance between the usually more susceptible male and the more resistant female nu/nu mouse. Microfilariae were found in the peripheral blood and the peritoneal cavity of CGN-treated male and female nu/nu mice and in the peritoneal cavity of male but not female nu/+ mice. Fewer larval granulomas were recovered from the peritoneal cavity of treated mice. CGN-treated, parasitized nu/+ and nu/nu mice showed high titers of IgM and IgG antibodies. An experimental compound, CGP 20376, showed 100% larvicidal activity following the administration of a single dose of 20 mg/kg to CGN-treated mice. From this study, we conclude that macrophages alone or in conjunction with other cells are actively involved in the resistance of mice to B. malayi L3. PMID- 1589434 TI - Light and scanning electron microscopical observations of the daughter rediae of Echinostoma trivolvis (Trematoda). PMID- 1589433 TI - Trypanocidal drugs and their effect on parasitaemia, specific IgG production and protective immunity in rats infected with Trypanosoma lewisi. AB - In rats infected with Trypanosoma lewisi, parasitaemia normally resolves by day 32; thereafter, the rodents become solidly immune to re-infection. Rats treated on day 5 of infection with a single i.m. dose of 35 mg/kg of the trypanocidal drug ethidium bromide (EB) had recovered from parasitaemia by day 12, whereas berenil (BE) given at 100 mg/kg, more than twice the recommended dose, had no effect on parasitaemia. However, rats treated for 4 consecutive days beginning on day 5 of infection with Lampit (LA) and Radanil (RA) at 350 mg/kg showed no parasitaemia on days 16 and 20, respectively. EB was the most effective drug in lowering the total IgG antibody as compared with the control animals, whose specific IgG titres remained elevated for over 200 days after the parasitaemia had been cleared. LA also significantly reduced the antibody levels through day 240, whereas RA only transitorily depressed the antibody levels on days 20 and 30. BE, which had no effect on parasitaemia, correspondingly failed to depress the total IgG levels. Re-challenge infection of the drug-treated, recovered animals on day 240 (208 days after the normal resolution of the infection) revealed that except for the EB group, which displayed transitory parasitaemia for 4 days, other treated and control rats completely resisted the challenge; pre challenge antibody titres were lower than 1:160 in EB-treated animals in contrast to the levels of 1:320 or higher measured in the other drug-treated and control animals, which resisted the infection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589435 TI - Immediate deterioration of rabbit colon preparations by Entamoeba histolytica trophozoite lysates. PMID- 1589436 TI - Isolation of mother and daughter sporocysts of Trichobilharzia ocellata from Lymnaea stagnalis. PMID- 1589438 TI - Lamellar structure of the amoebocyte-producing tissue in Lymnaea truncatula infected with Fasciola hepatica. PMID- 1589437 TI - Brain-tissue cysts in rats infected with the RH strain of Toxoplasma gondii. AB - Virulent strains of the coccidian parasite Toxoplasma gondii become attenuated so as to survive and complete their life cycle; however, it is not known whether the attenuation process is attributable to an innate cystogenic capacity of the parasite or to host-induced mechanisms. This report presents direct evidence of RH cystogenesis in non-immunised Fischer rats and subsequent attenuation of RH pathogenicity in non-immunised mice following a single passage through rats. Taken together, these preliminary observations tend to suggest that at least one mechanism of T. gondii involves intermediate host attenuation. PMID- 1589439 TI - [The importance of lipases in the digestive tract for the hydrolysis of lipid excipients and enzyme substitution therapy]. PMID- 1589440 TI - Application of derivative resolution of UV spectra to the quality control of rifaximine and its possible impurities. AB - An UV spectrophotometric method with derivative resolution was developed for the analysis of rifaximine (a synthetic rifamycin) in the presence of potential impurities of synthesis and oxidation. The method was particularly suitable for the qualitative identification of the set of compounds and had good detection limits. PMID- 1589441 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1589442 TI - The role of eicosanoids in experimental and clinical gallbladder disease. AB - The mammalian gallbladder has been shown by many authors to synthesize and release arachidonic acid metabolites. Many factors influence gallbladder eicosanoid release including sex of the animal, neural influences, age of the animal, pathologic stimuli (gallstones, inflammation), chemical mediators, hormones and the presence of hypercholesterolemia. The net result of these factors is release of gallbladder eicosanoids which act as paracrine substances to influence the gallbladder physiologic functions of water transport and motility. This review examines the experimental in vivo and in vitro experimental studies that have examined the various factors that alter mammalian gallbladder eicosanoid release in normal and pathologic states. PMID- 1589443 TI - Intratumoral gamma-linoleic acid therapy of human gliomas. AB - In vitro and in vivo studies have shown that gamma-linoleic acid (GLA), arachidonic acid (AA) and eicosapentaenoic acid (EPA) can selectively kill tumor cells. In a clinical trial, the effectiveness of intratumoral administration of GLA in patients with gliomas was studied. Of the 6 patients treated, all showed substantial response to GLA as documented by computerized tomography. There were no acute side-effects due to the therapy. This report demonstrates that intratumoral administration of GLA is a possible approach to the treatment of human glial tumors. PMID- 1589444 TI - The measurement of the main PGE metabolite, 13,14-dihydro-15-keto prostaglandin E by radioimmunoassay using methyl oxime stabilization. AB - The measurement of 13,14-dihydro-15-keto prostaglandin E2 [PGEM] is complicated by the artefactual formation of compounds of the corresponding A series which are reactive towards protein. Existing methods of assay depend on the deliberate dehydration to the 'A' form followed by cyclization in alkaline solution to a bicyclic derivative which is stable and can be measured by radioimmunoassay. We report an alternative approach using methyl oximation of the 9- and 15-keto groups which confer stability on the molecule. This derivatization is simple and does not involve an active intermediate such as those of the PGA series. The antiserum for radioimmunoassay is raised against the methyl oxime form. The label is the methyl oxime of PGEM coupled to a tripeptide Pro-gly-tyr through the nitrogen in the proline ring. This is a linkage distinct from that used to raise the antiserum and thus is not preferentially recognized over the endogenous analyte; this results in a high sensitivity assay. The results correlated well with those from the bicyclic assay when both assays were used to measure the same samples of peripheral blood from women receiving a sustained release PGE pessary for ripening the cervix. The technique provides a rapid and reliable method for determining prostaglandin E metabolites. PMID- 1589445 TI - Sera from preeclamptic patients contain factor(s) that stimulate prostacyclin production by human endothelial cells. AB - A relative decrease in endothelial cell prostacyclin production may be pivotal in the genesis of preeclampsia. We determined the effect of sera from preeclamptic women on prostacyclin production by monolayers of normal term human umbilical vein endothelial cells. Endothelial cells were incubated with media containing serum from patients with preeclampsia, non-hypertensive, gestational age-matched pregnant controls, or normal non-pregnant controls (N = 7, all groups). 6-Keto prostaglandin F1 alpha, the stable metabolite of prostacyclin, was measured directly in the culture medium by radioimmunoassay. Treatment with preeclamptic sera, when associated with a statistically significant increase in prostacyclin metabolite production by endothelial cells. Thus, sera from women with preeclampsia stimulate rather than inhibit prostacyclin production by endothelial cells. We speculate that there is a factor in the sera of women with preeclampsia that functions to activate endothelial cells or which may play a role in the homeostatic mechanisms to balance reduced prostacyclin output in preeclampsia. PMID- 1589446 TI - Effects of increasing dietary linoleic acid on phospholipid fatty acid composition and eicosanoid production in leucocytes and gill cells of Atlantic salmon (Salmo salar). AB - Diets containing linoleic acid at 10, 25 and 45% of total dietary fatty acids were fed to three groups of post-smolt Atlantic salmon (Salmo salar) for 18 weeks. Incorporation of linoleic acid into membrane phospholipids of leucocytes and gills increased in response to dietary intake. In general, there was an increase in arachidonic acid and a decrease in eicosapentaenoic acid in the individual phospholipids of both cell types in response to increasing dietary linoleic acid. These changes in eicosanoid precursors were reflected in significantly increased plasma concentrations of 6-keto-PGF1 alpha and TXB2 in salmon given the highest dietary linoleic acid. In whole blood stimulated with the calcium ionophore A23187, LTB4, 12-HETE and TXB2 were significantly increased and 12-HEPE significantly decreased in response to increasing dietary linoleic acid. In isolated gill cells stimulated with A23187, 12-HEPE, 12-HETE, 14-HDHE and TXB2 were all decreased in response to increasing dietary linoleic acid, although the ratio of 12-HEPE/12-HETE was also decreased. PMID- 1589447 TI - Synergism between PGE1-metabolites(13,14-dihydro-prostaglandin E1, 15-keto prostaglandin E1, 15-keto-13,14-dihydro-prostaglandin E1) and nitric oxide (NO) on platelet aggregation. AB - A synergistic antiplatelet effect between prostaglandins (PG), cAMP-stimulators and nitric oxide (NO), a cGMP-stimulator, has already been described. Data on a synergism between NO and the metabolites of PGE1, however, are lacking so far. We therefore tested the antiplatelet activity of the metabolites of PGE1 alone and their synergism with NO on human platelets of 8 healthy volunteers in vitro. 13,14-DH-PGE1 (ID 50 = 10.8 ng/ml platelet rich plasma (PRP)) was the only PGE1 metabolite inhibiting the ADP-induced platelet aggregation, its efficacy being 76.4% of the parent compound PGE1 (ID 50 = 8.25 ng/ml PRP). NO (ID 50 = 0.52 microM) also inhibited platelet aggregation. The combined addition of 13,14 dihydro-prostaglandin E1 (13,14-DH-PGE1) and NO caused an additive effect. The other PGE1-metabolites tested, 15-keto prostaglandin (15-K-PGE1) (ID 50 = 16.2. micrograms/ml PRP) and 15-keto-13,14-dihydro-prostaglandin(15-K-13,14-DH-PGE1) (ID 50 = 14.8 micrograms/ml PRP), neither had any relevant antiaggregatory capacity themselves nor a synergistic effect with NO. These findings could be of clinical relevance as a NO-synergism may occur not only with therapeutically administered PGE1 but also with its biologically active metabolite 13,14-DH-PGE1. PMID- 1589448 TI - Probable influence of ova and embryo prostaglandins in the differential ovum transport in pregnant and cycling rats. AB - In this study we explored the possible underlying mechanism(s) of the differential transport of unfertilized and fertilized ova in cycling and pregnant rats. The number of ova recovered from rat oviducts and uterus was not significantly different in estrus, metestrus and diestrus but dropped sharply at proestrus. When estrus rats were injected with indomethacin (10(-6)), a well known inhibitor of cyclooxygenase, delivered into both ovarian bursae, and sacrificed next day at metestrus, the number of ova in the oviduct was significantly smaller (p less than 0.025) than in controls at metestrus. On the other hand, when diestrus rats were injected with PGE1 (10(-6)) delivered into both ovarian bursae, and sacrificed next day at proestrus, no ova were found in the oviducts, and only a few of them were in the uterus. When fertilized ova were recovered from oviducts and uteri at day 4 of pregnancy (corresponding to proestrus of cycling rats) an average of 4 embryos were still found in the oviducts, proving a differential ovum transport between cycling and pregnant rats. In order to establish if there exists any ova or embryo releasing factor responsible for this difference, the prostaglandins released to the incubation medium by ovum or 3-day embryo were measured. Unfertilized ova produced significantly more PGE1 (p less than 0.05) than PGE2 or PGF2 alpha. The same pattern of PG production was observed with incubated embryos, but in this case the amount of PGE1 released was significantly higher (p less than 0.01) that the PGE1 released by unfertilized ova.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589449 TI - Nicardipine reduces the levels of leukotriene C4 and prostaglandin E2, following different ischemic periods in rat brain tissue. AB - Ischemic depolarization of nerve membranes is associated with a rapid influx of calcium into the cell, resulting in production of arachidonic acid (AA) metabolites. These metabolites, particularly leukotriene C4 (LTC4) have a very potent vasoconstrictor effect on cerebral arteries inducing vasogenic edema that may damage the ischemic penumbra. Calcium antagonists are assumed to prevent or reduce metabolic disturbances associated with ischemia. In this study, after developing an experimental animal model simulating the concept of the ischemic penumbra in the rat, the levels of LTC4 and prostaglandin E2 (PGE2) produced in the forebrain following different ischemic periods, such as 4th, 15th, 60th and 240th min were measured by a bioassay method, including 6 rats for each ischemic group. Then the effect of the 1-4 dihydropyridine nicardipine (1 mg/kg) on these mediators was investigated by giving it to the rat 30 min before the development of the ischemic model in each corresponding group (n = 6). We showed that nicardipine significantly reduced the high levels of LTC4 and PGE2 in the 4th min and 4th h of cerebral ischemia (p less than 0.005, p less than 0.0005). So it may be concluded that institution of nicardipine may be helpful in protecting the ischemic penumbra during the early hours of cerebral ischemia. PMID- 1589450 TI - Effects of prostaglandins and of leukotriene C4 on the metabolism of labelled glucose in uteri isolated from ovariectomized-diabetic rats. Influences of 17 beta-estradiol and of insulin. AB - The influences of exogenous PGE1, PGE2, PGF2 alpha, LTC4 and insulin (INS) on glucose oxidation in uterine strips isolated from ovariectomized-diabetic (OVD) and ovariectomized-estrogenized-diabetic (OVED) rats, were studied. The spayed animals were made diabetic by a single injection of streptozotocin (65 mg.kg-1 body weight). The effects of prostaglandins were studied in the presence of indomethacin (INDO) in the incubation medium and the effects of LTC4 in the presence of INDO and nordihydroguaretic acid (NDGA). These procedures were followed in order to avoid the possible influences of endogenous derivatives of arachidonic acid formed by the activity of cyclooxygenase and of lipoxygenases. INDO and NDGA did not modify significantly the formation of 14CO2 from U-14C glucose in uteri from OVD and from OVED rats. INS (0.5 U.ml-1) augmented significantly labelled glucose metabolism, both in OVD as well as in OVED rats. On the other hand, added PGE1, PGE2, PGF2 alpha or LTC4 failed to alter glucose metabolism in uteri from OVD rats. Only PGE1 was able to increase significantly (p less than 0.05) 14CO2 production from labelled glucose in uterine strips from OVED rats. In OVD rats the stimulatory action of INS on uterine glucose metabolism was significantly enhanced by exogenous PGE1, but not modified by PGE2, by PGF2 alpha or by LTC4. PGE1, PGE2 and LTC4 sensitized uterine strips obtained from OVED rats to the effects of INS. The possible importance of PGE1 in improving uterine glucose metabolism in diabetic animals is discussed. PMID- 1589451 TI - A comparative study between cod liver oil and liquid lard intake on intraocular pressure on rabbits. AB - Cod liver oil administered intramuscularly (0.2 ml/day) lowered intraocular pressure (IOP) of the rabbit from 21 mmHg to 18 +/- 0.4 mmHg (p less than 0.05 n = 8). A higher dose of cod liver oil (1 ml) further lowered intraocular pressure to 14.5 +/- 0.3 mmHg which remained at this level for up to 80 days when the rabbits were sacrificed. Intramuscular injections of liquid lard did not alter IOP in rabbits. When treatment with cod liver oil was stopped, IOP rose to baseline levels. Topical treatment with cyclooxygenase inhibitors had no effect on the IOP lowering effect of cod liver oil. Topical treatment of rabbit eyes with 1% aspirin solution twice daily (up to 28 days) and flurbiprofen t.i.d. (up to 15 days) caused no alteration in the decrease in IOP seen with intramuscular cod liver oil treatment for up to 28 and 15 days respectively. PMID- 1589453 TI - [The immunobiology of eosinophilic granulocytes]. PMID- 1589452 TI - Effects of saturated fatty acids on prostaglandin E 9-keto-reductase. AB - We examined the effects of three saturated fatty acids (myristic acid 14:0, palmitic acid 16:0, and stearic acid 18:0) on prostaglandin E 9-ketoreductase (PGE-9-KR, EC 1.1.1.189), which catalyzes the conversion of prostaglandin E2 (PGE2) into prostaglandin F2 alpha (PGF2 alpha). Palmitic acid inhibited PGE-9-KR activity dose-dependently, whereas the other two fatty acids had no effect. In spite of the structural similarity of these fatty acids, our findings suggest that, of the three, only palmitic acid has an inhibitory effect on PGE-9-KR. PMID- 1589454 TI - [A simple production method for liposomes and experimental production of hemoglobin and insulin liposomes. An overview of a series of experiments for production of liposomes intended for parenteral and preoral administration]. PMID- 1589455 TI - [Molstar--modeling software for teaching]. PMID- 1589456 TI - Non-ionizing radiation safety: radiofrequency radiation, electric and magnetic fields. PMID- 1589457 TI - An algorithm for maximizing the probability of complication-free tumour control in radiation therapy. AB - New radiobiological models are used to describe tumour and normal tissue reactions and to account for their dependence on the irradiated volume and inhomogeneities of the delivered dose distribution and cell sensitivity. The probability of accomplishing complication-free tumour control is maximized by an iterative algorithm. The algorithm is demonstrated by applying it to a one dimensional (1D) tumour model but also to a more clinically relevant 2D case. The new algorithm is n-dimensional so it could simultaneously optimize the dose delivery in a 3D volume and in principle also select the ideal beam orientations, beam modalities (photons, electrons, neutrons, etc) and optimal spectral distributions of the corresponding modalities. To make calculation time reasonable, 2D-3D problems are most practical, and suitable beam orientations are preselected by the choice of irradiation kernel. The energy deposition kernel should therefore be selected in order to avoid irradiation through organs at risk. Clinically established dose response parameters for the tissues of interest are used to make the optimization as relevant as possible to the clinical problems at hand. The algorithm can be used even with a poorly selected kernel because it will always, as far as possible, avoid irradiating organs at risk. The generated dose distribution will be optimal with respect to the spatial distribution and assumed radiobiological properties of the tumour and normal tissues at risk for the kernel chosen. More specifically the probability of achieving tumour control without fatal complications in normal tissues is maximized. In the clinical examples a reduced tumour dose is seen at the border to sensitive organs at risk, but instead an increased dose just inside the tumour border is generated. The increased tumour dose has the effect that the dose fall off is as steep as possible at the border to organs at risk. PMID- 1589458 TI - Photon field quantities and units for kernel based radiation therapy planning and treatment optimization. AB - The problem of choosing radiation quantities and units for energy deposition kernels and their associated kernel densities is treated with the aim of making them consistent with related classical radiation quantities and units such as restricted mass stopping powers and mass attenuation coefficients. It is shown that it is very useful to define the kernels h(r), in terms of the quotient of the mean specific energy imparted to the medium by the radiant energy incident on a volume element centred at the origin of the kernel. The basic building block used to generate these kernels is the point energy deposition kernel, h(p), describing the spatial distribution of the energy imparted by a photon interacting at a point in a medium. This will allow the kernels to be regarded as generalizations of the traditional mass stopping and attenuation coefficients, which in detail describe the spatial distribution of the mean energy deposition around an interaction site. As a consequence, the irradiation or kernel density, f(r) should be expressed in terms of the radiant energy incident per unit volume of the medium. It is shown that the kernel density is equal to minus the divergence of the incident unattenuated vectorial energy fluence, and it therefore acts as an irradiation density for the incident vectorial energy fluence. The microscopic kernels or the irradiation density may thus be viewed as a perfect 'sink' distribution to the required incident photon energy fluence which is totally absorbed at f(r), and instead replaced by the kernels which describe the detailed energy deposition in the medium in coordinates centred at the sinks. From these definitions the required incident energy fluence from an external radiation source used for treatment realization can be determined directly by projecting the irradiation density on the relevant positions of the radiation source. This procedure has the valuable property that maximal calculational accuracy is achieved in the tumour because the irradiation density has non-zero values only in the tumour, and the accuracy of the kernel is highest at its origin. PMID- 1589459 TI - The use of India ink as an optical absorber in tissue-simulating phantoms. PMID- 1589460 TI - Whose journal is this? PMID- 1589461 TI - A study of discomfort with electrical stimulation. AB - The primary purpose of this study was to investigate the influence of personality variables and contractile forces on magnitude estimates of pain unpleasantness and pain intensity during varying levels of neuromuscular electrical stimulation (NMES). Thirty volunteers, according to their scores on a preferred coping-style questionnaire, were assigned to one of two groups, one designated "monitors" (information seekers) and the other designated "blunters" (information avoiders). All subjects were administered varying levels of two types of NMES, one causing both afferent stimulation and muscle contraction and one causing only afferent stimulation. Subjects judged the intensity and unpleasantness of each current type using magnitude estimation. Data were analyzed using a 2 x 2 x 2 x 3 (coping style x current type x pain descriptor x current level) analysis of variance. The results indicated that the rate of increase of magnitude estimates for unpleasantness and pain intensity that corresponded to increases in current were dependent on (1) the preferred coping style of the subject, (2) whether the stimulus caused a muscle contraction, and (3) whether the subject was judging the intensity or the unpleasantness of the applied stimulus. Behavioral styles appear to affect how subjects characterize the discomfort associated with NMES, and involuntary muscle contractions contribute to the discomfort felt from NMES. These results suggest that interventions tailored to a preferred coping style may increase a subject's level of tolerance to NMES and thus provide a more beneficial treatment. PMID- 1589462 TI - Incidence of common postural abnormalities in the cervical, shoulder, and thoracic regions and their association with pain in two age groups of healthy subjects. AB - The purposes of this study were to identify the incidence of postural abnormalities of the thoracic, cervical, and shoulder regions in two age groups of healthy subjects and to explore whether these abnormalities were associated with pain. Eighty-eight healthy subjects, aged 20 to 50 years, were asked to answer a pain questionnaire and to stand by a plumb line for postural assessment of forward head, rounded shoulders, and kyphosis. Subjects were divided into two age groups: a 20- to 35-year-old group (mean = 25, SD = 63) and a 36- to 50-year old group (mean = 47, SD = 2.6). Interrater and intrarater reliability (Cohen's Kappa coefficients) for postural assessment were established at .611 and .825, respectively. Frequency counts revealed postural abnormalities were prevalent (forward head = 66%, kyphosis = 38%, right rounded shoulder = 73%, left rounded shoulder = 66%). No relationship was found between the severity of postural abnormality and the severity and frequency of pain. Subjects with more severe postural abnormalities, however, had a significantly increased incidence of pain, as determined by chi-square analysis (critical chi 2 = 6, df = 2, P less than .05). Subjects with kyphosis and rounded shoulders had an increased incidence of interscapular pain, and those with a forward-head posture had an increased incidence of cervical, interscapular, and headache pain. PMID- 1589463 TI - Goal attainment scaling as a measure of change in infants with motor delays. AB - Goal attainment scaling (GAS) is an individualized criterion-referenced measure of change that has several unique features, compared with the behavioral objective, and five possible levels of attainment for each goal. The validity of GAS as a measure of motor change was investigated in 65 infants, 3 to 30 months of age, with motor delays. For each infant, two goals to be attained within a 6 month period of intervention were established. After the 6-month period, the mean GAS T-score of 55.4 was significantly higher than the expected mean of 50. This finding indicated that the infants' motor change exceeded the therapists' expectations. Neither the type nor the category of goal influenced the therapists' ability to select outcomes that the infants were capable of achieving. Because moderate and low correlations were found between GAS T-scores and Peabody gross motor and fine motor change scores, the two assessments appear to measure different aspects of motor development. Selected child, family, and program variables were examined as sources of bias in GAS T-scores. Motor delay was the only variable that biased GAS T-scores; infants who were less delayed had higher GAS T-scores. The results indicate that GAS was responsive to change in individualized motor goals and support the model of GAS as an idiosyncratic measure. The unique features of GAS offer advantages for measurement of motor change compared with the behavioral objective and norm-referenced developmental scales. PMID- 1589464 TI - The effect of two intensities of massage on H-reflex amplitude. AB - The purposes of this study were (1) to investigate the effectiveness of two different levels of massage on the depression of spinal motoneuron excitability (as demonstrated by peak-to-peak H-reflex amplitude changes), (2) to investigate the presence of any gender effects in relation to massage, and (3) to describe a method used to quantify the amount of pressure exerted during two different intensities of massage. Two levels of massage were quantified and defined as light massage (LM) and deep massage (DM). These levels of massage corresponded to pressures of 1.25 and 2.50 kPa (5 and 10 in H2O), respectively. The therapist, before beginning the investigation, was trained to deliver these pressures. Ten peak-to-peak H-reflex recordings were elicited from the triceps surae muscle of each of 20 neurologically healthy subjects (10 male, 10 female) (mean age = 22.6 years) during five control and the two massage conditions. Each condition was 3 minutes in duration. Significant differences were found among the resulting means. The peak-to-peak H-reflex amplitudes recorded during the DM condition were reduced in comparison with those recorded during the LM condition. The peak-to peak H-reflex amplitudes during both massage conditions were reduced in comparison with those recorded during the control conditions. These changes were noted against a stable M-response. This suggests that the mechanism involved in the observed inhibitory response is pressure sensitive, with DM bringing about a greater inhibitory response than did LM. No differential effects attributable to gender differences were found. These results will serve to define massage characteristics in an ongoing study investigating the effect of massage in persons with a spinal cord injury. PMID- 1589465 TI - Long-term stability of hand-held dynamometric measurements in children who have myelomeningocele. AB - The long-term stability of hand-held dynamometric measurements was assessed in 30 muscle groups of 12 children with myelomeningocele, before and after a 23-day interval. Measurements from a majority of the muscle groups had excellent stability, based on statistical indicators of association (Pearson Product-Moment Correlation Coefficients, r =.76-.98) and agreement (intraclass correlation coefficients, ICC = .75-.99). Muscle groups with lower long-term stability were the right and left wrist extensors and flexors, the left hip adductors and extensors, the left knee flexors, and the right and left knee extensors. Upper extremity muscle groups had higher long-term stability than did lower-extremity muscle groups. The results indicate that the dynamometric measurements were highly reliable when the test-retest interval was 23 days. Other researchers have previously shown high reliability for these measurements over shorter periods of time. Improved reliability might be obtained by supporting the lower extremity during hip extension tests; padding the dynamometer end pieces, especially when testing over bony prominences; and using a smaller, digital dynamometer. The hand held dynamometer appears to warrant use and further investigation with pediatric populations. PMID- 1589466 TI - Safety and liability. PMID- 1589467 TI - Orr Esrey Reynolds 1920-1991. PMID- 1589468 TI - Alterations in glomerular hemodynamics and tubular reabsorption after 24 hours head down-tilt and following acute return to orthostasis. PMID- 1589469 TI - Effect of 14 day head-down tilt on renal function and vascular and extracellular fluid volumes in the conscious rat. PMID- 1589470 TI - Single hindlimb weight bearing by the rat during simulated microgravity. PMID- 1589471 TI - A computer simulation study of preadaptation of the circulation by removal of different blood volumes to counteract central fluid shifts. PMID- 1589472 TI - Dependence of blood volume changes on oral sodium uptake. PMID- 1589473 TI - Intramuscular pressure measurement as an index of torque during dynamic exercise. PMID- 1589474 TI - Echocardiographic evaluation of cardiac function during parabolic flight. PMID- 1589475 TI - Data acquisition system for the artificial gravity simulator (AGS). PMID- 1589476 TI - Spatial organization of digestive and barrier functions of the small intestine (new hypotheses and data). PMID- 1589477 TI - Short radius centrifuge as a method in long-term space flights. PMID- 1589478 TI - Prognostication of flyer's +Gz tolerance on the base of static muscular strength endurance. PMID- 1589479 TI - High-G cardiovascular physiology. PMID- 1589480 TI - Metabolic bases of +Gz duration tolerance. PMID- 1589481 TI - Enhanced aerobic capacity and increased acceleration stress: is their interaction a problem for pilots? PMID- 1589482 TI - Brain biochemical factors related to G-LOC. PMID- 1589483 TI - Aeromedical problems in the high-G environment: a look at the future. PMID- 1589484 TI - Positive pressure breathing for G: evolution and promise. PMID- 1589485 TI - Protecting the pilot during high-G loading. PMID- 1589486 TI - Advanced +Gz protection systems and their physiologic bases. PMID- 1589487 TI - Cell in gravitation field. PMID- 1589488 TI - Computer modelling the effects of gravity on the cardiovascular system. PMID- 1589489 TI - Computer simulation analysis of the effects of countermeasures for reentry orthostatic intolerance. AB - Fluid loading is a countermeasure currently in routine use to improve the g tolerance of crewmembers during reentry and return of Shuttle flights. However, its effectiveness diminishes with mission duration. Countermeasures that will be effective on long-duration flights are needed and are presently under development. This paper discusses the application of computer simulation in the analysis of the effects of countermeasures for reentry orthostatic intolerance. The results suggest improvements upon the fluid loading countermeasure currently in use. PMID- 1589490 TI - Mathematical modelling of +Gz acceleration induced stresses in the human ventricle myocardium. PMID- 1589491 TI - The role of subclinical cardiovascular diseases in high-G flying: a mathematical modeling approach. PMID- 1589492 TI - The lung at high G: major factors in modelling. PMID- 1589493 TI - Mathematical modeling of the cardiovascular system to study acceleration stress. PMID- 1589494 TI - Mathematical modeling of the otoliths and semicircular canals as the systems with distributed parameters. PMID- 1589495 TI - Increased intracranial pressure in humans during simulated microgravity. PMID- 1589496 TI - Cerebral blood flow velocity increases with acute head-down tilt of humans. PMID- 1589497 TI - Gas exchange and cardiovascular responses to tilting during graded exercise. PMID- 1589498 TI - Epidermal growth factor induced signal transduction in A431 cells is influenced by altered gravity conditions. PMID- 1589499 TI - Blood pressure, blood volume regulating hormone and electrolyte responses after a 28-day confinement period in a hyperbaric chamber at 1.5 ATA. PMID- 1589500 TI - Water intake, urine volume, Ca intake, and urine Ca during 10 days bed-rest in young woman. PMID- 1589501 TI - Effects of 10-days bed rest and moderate training on LBNP tolerance in young woman. AB - The tolerable capacity against LBNP was decreased by bed rest and recovered by physical training. The tolerable capacity was related to VO2max and LVEDd. However, the LBNP tolerance capacity should be primarily limited by factors involving venous return in LVEDd, because VO2max must be controlled by the factors. PMID- 1589502 TI - Effects of moderate physical training after 10 days horizontal bed-rest on peak VO2 and cardiorespiratory functions during submaximal supine and sitting exercise in young subjects. PMID- 1589503 TI - Interstitial space dynamics: simulated response to LBNP. PMID- 1589504 TI - Peripheral hemodynamic assessment during LBNP for the evaluation of the vascular deconditioning induced by a long term HDT. PMID- 1589505 TI - Mathematical modeling of human cardiovascular response to LBNP. PMID- 1589506 TI - Physical state, equilibrium function and vestibulo- motor reflexes in the rats after space flights on board biosatellites of Cosmos series. PMID- 1589507 TI - +Gx-tolerance following one-year real and simulated microgravity. PMID- 1589508 TI - Changes in voluntary eating behavior during a 28 day head-down bed rest experiment: preliminary results. PMID- 1589509 TI - Experiment "Chlamydomonas" aboard biosatellite "Cosmos-2044". PMID- 1589510 TI - Noradrenergic and cholinergic innervation of spleen in the rats developed under changed gravity. PMID- 1589511 TI - Morphology and histochemistry of spinal cord and soleus muscle in rats grown under hypergravity. PMID- 1589512 TI - Neuron-glia-capillary system in spinal cord of rats after 14-day space flight. PMID- 1589513 TI - Results of immunological experiments aboard the Cosmos biosatellites and problems in space immunology. PMID- 1589514 TI - Effect of space flight on immune responses: bone marrow cell response to colony stimulating factor and leukocyte subsets. PMID- 1589515 TI - Dynamics of structural changes in skeletal muscle neuromuscular junctions of rats under the influence of the space flight factors. PMID- 1589516 TI - Gravitational effects on Paramecium and Loxodes. PMID- 1589517 TI - Influence of weightlessness on erythroid system in monkeys. PMID- 1589518 TI - Erythrocyte functional status and adrenoreactivity in monkeys after space flight and control experiment. PMID- 1589519 TI - Elemental bone composition of the rats flown in "Cosmos 2044" biosatellite. PMID- 1589520 TI - Metabolic study in primates exposed to microgravity on board "Cosmos" biosatellites. PMID- 1589521 TI - Metabolism in cosmonauts: results of blood biochemistry studies in crewmembers of 7 prime missions to the orbital "Mir" station. PMID- 1589522 TI - Lipid peroxidation and the system of antioxidant protection in rats after space flights of varying duration. PMID- 1589523 TI - Circulation in primates exposed to microgravity aboard the "Cosmos" biosatellites. PMID- 1589524 TI - The evaluation of biological efficiency of electromagnetic fields generated by implanted radiotelemetric transmitters used in space research on animals. AB - The study was carried out in 50 male rats abdominally implanted with biotelemetric systems (BTS) or mock-up. The animals were provided with 12/12 light/dark schedule during 6-week experiment. The electromagnetic field (EMF) frequency was 455 kHz, magnetic induction near transducer was about 10(-2) mT. Circadian rhythm of the body temperature and locomotor activity was controlled in course of the experiment. The latter been finished, some tissues and the blood of the animals have been sampled to test corticosterone, testosterone, T3, T4 level in serum with radioimmunoassay and membrane permeability for Ca2+, Na+, K(+) ATPase activity and charge changes in liver microsomes was detected. The probable ways of the EMF influence on whole body are discussed. PMID- 1589525 TI - Electromagnetic and magnetic fields as active environmental factors in biosatellite. PMID- 1589526 TI - Hybrid formation and metabolism of plant cell protoplasts under microgravity. PMID- 1589527 TI - Experiments with suspended cells on the Space Shuttle. AB - Spaceflight experiments since 1981 have demonstrated that certain cell functions are altered by micro-g. Biophysical models suggest that cell membranes and organelles should not be affected directly by gravity, however, the chemical microenvironment surrounding the cell and molecular transport could be altered by reduced gravity. Most experiments have used suspended live cells in small chambers without stirring or medium exchange. Flight results include increased attachment of anchorage-dependent human cells to collagen coated microcarriers, reduced secretion of growth hormone from pituitary cells, decreased mitogenic response of lymphocytes, increased Interferon-alpha by lymphocytes, increased Interleukin-1 and Tumor Necrosis Factor secretion by macrophages. Related experiments on cells immediately postflight and on procaryotic cells have shown significant changes in secretory capacity, cell proliferation, differentiation and development. Postulated mechanism include altered cell-cell interactions, altered calcium ion transport, effects on cell cytoskeleton, transport of transmitters and interactions with receptors. The discussion includes use of new molecular methods, considerations for cell environmental control and a preview of several experiments planned for the Shuttle and Spacelab flights to study the basic effects of microgravity on cellular physiology and potential interactions of spaceflight with radiation damage and cellular repair mechanisms. PMID- 1589528 TI - Light-potentiated maize root gravitropism: is perception localized in the root cap? PMID- 1589529 TI - Receptor-mediated endocytosis in osteoblastic cells under "gravitational stress". PMID- 1589530 TI - Ultrastructural aspects of chondrogenesis in "cells" flight hardware. PMID- 1589531 TI - Gravitational effects on mammalian cells. PMID- 1589532 TI - Neurogram analysis tested on synthetized multiunit firing patterns. PMID- 1589533 TI - Responses of gravity level variations on the NASA/JSC bioreactor system. PMID- 1589534 TI - Gravitational physiology in the 1990s. PMID- 1589536 TI - Aortic wave reflection and input impedance as a function of posture in a chronic primate model. PMID- 1589535 TI - Delivery of recombinant human growth hormone to rats during exposure to microgravity on NASA Space Shuttle Discovery. PMID- 1589537 TI - Ventricular/vascular coupling under hypergravity in a chronically instrumented conscious primate model. PMID- 1589538 TI - Theory of mechanical intracranial hypertension under rapid onset rate (ROR) acceleration modeling of intracerebral blood flow. PMID- 1589539 TI - Muscular adaptations induced by dobutamine and their influence on G-tolerance in miniature swine. PMID- 1589540 TI - Rapid onset rate, G loss of consciousness (ROR G.LOC): mechanical intracranial hypertension. A new concept? PMID- 1589541 TI - Entrainment of circadian rhythms in the rat by daily one hour G pulses. PMID- 1589542 TI - Heart rate ultradian rhythm in pilots subjected to hypergravitational stress. PMID- 1589543 TI - Lactacidemia in non human primates exposed to repeated high sustained +Gz acceleration. PMID- 1589544 TI - Changes in the renin-angiotensin response of non-human primates exposed to repeated high sustained +Gz acceleration. PMID- 1589546 TI - Venous return, gravitationnal stress and physical training. PMID- 1589545 TI - Hemodynamic effects of dobutamine and their influence on G-tolerance in pigs. PMID- 1589547 TI - Gravity and the ontogeny of animals. PMID- 1589548 TI - Control of circulatory function in altered gravitational fields. PMID- 1589549 TI - Gravity and the regulation of carbohydrate metabolism. PMID- 1589550 TI - Adaptive capacities of mammals in weightlessness and hypergravity. PMID- 1589551 TI - An assessment of suspension systems: models that reproduce responses to weightlessness. PMID- 1589552 TI - Designing methods for musculoskeletal conditioning in weightlessness. AB - There is an immediate need to find methods to combat the skeletal muscle deconditioning that occurs in microgravity. Important features to be considered for any ergometer or exercise method to be used as a countermeasure against musculoskeletal deconditioning in space include heavy muscular loading of the postural muscles of the lower limbs and that eccentric and concentric muscle activations can be performed. Those are major requirements to produce optimal gains in strength and muscle mass at 1-g and probably to counteract muscle atrophy and strength loss in microgravity. Resistance exercise with a strength ergometer, using the fly-wheel principle was carried out at a low oxygen cost and required no external power supply. We have developed a resistance training system employing this ergometer so that force and power production easily can be monitored and calibrated. It is suggested that the features of this ergometer meet the presented requirements for use during long-term space missions. PMID- 1589553 TI - Pulmonary function in microgravity. AB - We report the successful collection of a large quantity of human resting pulmonary function data on the SLS-1 mission. Preliminary analysis suggests that cardiac stroke volumes are high on orbit, and that an adaptive reduction takes at least several days, and in fact may still be in progress after 9 days on orbit. It also suggests that pulmonary capillary blood volumes are high, and remain high on orbit, but that the pulmonary interstitium is not significantly impacted. The data further suggest that the known large gravitational gradients of lung function have only a modest influence on single breath tests such as the SBN washout. They account for only approximately 25% of the phase III slope of nitrogen, on vital capacity SBN washouts. These gradients are only a moderate source of the cardiogenic oscillations seen in argon (bolus gas) and nitrogen (resident gas), on such tests. They may have a greater role in generating the normal CO2 oscillations, as here the phase relationship to argon and nitrogen reverses in microgravity, at least at mid exhalation in those subjects studied to date. Microgravity may become a useful tool in establishing the nature of the non gravitational mechanisms that can now be seen to play such a large part in the generation of intra-breath gradients and oscillations of expired gas concentration. Analysis of microgravity multibreath nitrogen washouts, single breath washouts from more physiological pre-inspiratory volumes, both using our existing SLS-1 data, and data from the upcoming D-2 and SLS-2 missions, should be very fruitful in this regard.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589554 TI - [On trigger experience of a group of anxiety neurotics--its psychopathology and therapeutic utilization]. AB - There is a group of anxiety neurotics, characterized by trigger experience (specific experience that triggers the anxiety attack at the initial phase of the illness). These are the patients, whose chief clinical manifestation is anxiety attack and anticipatory anxiety, with the additional feature of the recognizable trigger experience. Because of this additional feature, psychotherapeutic approach is often made in these cases. In this article, we present 7 such cases, in which we attempted psychotherapeutic approach with the special emphasis on the reconstruction of their trigger experience. Then we discuss the characteristics of the trigger experience and the therapeutic utilization of its reconstruction. The basic structure of their trigger experience is as follows. 'The experience of being taken by surprise, and shaken off something, which they believed to be, or tried to believe to be, firm and secure to them'. This 'something' is mainly concerned with their self-image. The self-image of 'the person who is healthy and has nothing to do with death, disease and madness' is common to all cases. But they also get different features, and can be divided into 3 subtypes, according to the difference in their self-images. 1. Compulsive-phobic type (case 1, 2, 3); 'the harmless person without impulsiveness and aggression'. 2. Hysterical type (case 4, 5, 6); 'the good mother, doing their best for their children, suppressing their own desire'. 3. Narcissistic type (case 7); 'the manly, energetic and ambitious person'. Symbolically speaking, in the contrast of 'ordinariness and extraordinariness', 'something familiar and something unfamiliar and uncanny', they exclude 'extraordinariness, something unfamiliar and uncanny', and rely only on 'ordinariness, something familiar'. They are clinging to the world of 'ordinariness', and thrown into confusion and anxiety when they catch a glimpse of the world of 'extraordinariness', which they have tried desperately to exclude from their life until then. Therapeutic efficacy of the reconstruction of the trigger experience is summarized in 3 factors as follows. 1. Explanation of their pathogenesis. It is a grave shock to them that the anxiety attack has occurred 'out of the blue' and 'with no reason'. In addition to the general explanation of the pathogenesis of anxiety neurosis, it is a relief to them that the explanation for each individual is possible. 2. Reinforcement of the transference cure ('faith care'). By putting into words what they did not make explicit until then, their belief in the therapist is intensified, and the function of the therapist of endowing them with the basis of security is reinforced.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1589555 TI - [A computer-assisted EEG study on psychotropic properties of antiparkinsonian drugs]. AB - For the purpose of determining psychotropic properties of antiparkinsonian substances, the author has carried out a quantitative analytic study on EEG changes induced by six marketed antiparkinsonian drugs in young normal volunteers. The drugs were six antiparkinsonian agents, l-dopa (LDP) 100 mg, trihexyphenidyl (THP) 2 mg, 4 mg, biperiden (BPD) 1 mg, 2 mg, 5 mg, mazaticol (MZC) 4 mg, 8 mg, amantadine (AMD) 100 mg, bromocriptine (BMC) 1.25 mg, 2.5 mg, and amitriptyline (ATP) 25 mg, haloperidol (HPD) 3 mg, diazepam (DZP) 3 mg, inert placebo (PLB) as active and inactive controls. They were orally given to six healthy male volunteers respectively with two weeks interval and pre-drug, one, three, six hour post-drug EEGs were recorded and analyzed using our computer system with the periodgram technique. Placebo-controlled differences between pre- and post-drug EEGs were statistically treated with the principal component analysis. THP, BPD and MZC produced a marked decrease of alpha frequency associated with increases of slow and fast activities. In addition, MZC induced a slight delirious state with visual and auditory hallucinations at 8 mg in five of six subjects. EEG profiles of these drugs appeared very close to those of thymoleptics but the clinical observations suggest some psychodysleptic property of MZC at a higher dose. LDP provoked a decrease of lower alpha frequency and an increase of lower fast activity that may suggest central stimulant or mood elevating effects. BMC and AMD induced a decrease of slow activity associated with increases of higher alpha activity and lower fast activity in EEG and suggested their vigilance enhancing effects. Based on the current experience, it would be appropriate to use six EEG bands classification (delta, theta, lower alpha, higher alpha, lower beta, higher beta) instead of the fundamental four bands (delta, theta, alpha and beta) in pharmaco-EEG, as far as multivariate analysis of psychotropic drug profile is concerned. It must be noted that the higher part of alpha frequency present a completely different response from the lower part to the centrally effective drugs. Furthermore, psychiatrists should be as prudent as possible when prescribing antiparkinsonian drugs for prevention and treatment of drug induced extrapyramidalism. PMID- 1589556 TI - [A case of agoraphobia provoked by MR imaging]. PMID- 1589557 TI - [Adversary system and competence to stand trial in the Japanese criminal procedure]. PMID- 1589559 TI - Adipsic, but not anorectic, effect of fluprazine hydrochloride in rats. AB - The present experiment explored the anorectic and adipsic effects of fluprazine hydrochloride, a phenylpiperazine compound. Thirty-eight albino rats were randomly assigned either to a control saline group (six rats) or to groups (eight subjects each) receiving an IP dose of fluprazine in saline (1.25, 2.5, 5 or 10 mg/kg). No anorectic effect of the drug doses was observed 30, 60, 90, 120, 180 and 240 min, and 24 h after drug injection. However, water drinking was significantly decreased 30 min after drug administration, with 5 and 10 mg/kg, compared to saline. PMID- 1589558 TI - Relationship between drug plasma concentrations and psychomotor performance after single doses of ethanol and benzodiazepines. AB - In a placebo controlled, crossover study psychomotor effects of single doses of diazepam, 10 and 20 mg, flunitrazepam, 1 and 2 mg, as well as 0.9 g ethanol/kg body weight were investigated over a time period of 6 h in 12 healthy men. Blood samples were collected simultaneously with the test sessions to determine drug concentrations in plasma or blood. The ethanol dose caused the least performance impairment, followed by 10 mg diazepam. The most pronounced impairment was caused by 2 mg flunitrazepam, whereas 20 mg diazepam and 1 mg flunitrazepam caused intermediate impairment and were approximately equipotent on group level. Considerable interindividual differences with respect to maximal impairment following a particular drug treatment were observed, with poor correlation between individual maximal impairments and individual peak plasma concentrations of the drug. The maximal impairment in simple reaction time following the flunitrazepam treatments occurred earlier relative to the peak plasma concentration of the drug as compared to the diazepam treatments. This may indicate that acute tolerance develops differently for the two drugs. PMID- 1589560 TI - Locomotor responses to benzodiazepines, barbiturates and ethanol in diazepam sensitive (DS) and -resistant (DR) mice. AB - Diazepam-sensitive (DS) and -resistant (DR) mice were selectively bred for increased and reduced sensitivity to the ataxic effects of diazepam (40 mg/kg). Other response differences between DS and DR mice may reflect pleiotropic effects of the genes fixed during their selection. These mice were tested for their sensitivity to the locomotor stimulant effects of several doses of diazepam, flunitrazepam, pentobarbital, phenobarbital, and ethanol. DR mice were more sensitive than DS mice to the locomotor stimulant effects of all drugs except phenobarbital. These results largely support the hypothesis that a common biological mechanism mediates sensitivity to the stimulant effects of sedative hypnotic drugs. Receptor mediation of the benzodiazepine effects was examined by administering the benzodiazepine receptor antagonist, RO15-1788. Locomotor depression produced by diazepam and flunitrazepam in DS mice was blocked by RO15 1788. However, while the locomotor stimulation produced by diazepam in DR mice was antagonized, the stimulant effect of flunitrazepam was not. This suggests that binding of flunitrazepam to the GABAA-benzodiazepine receptor is not necessary for production of locomotor stimulation. PMID- 1589561 TI - Effects of calcitonin on human auditory and visual evoked brain potentials. AB - Besides its Ca(++)-regulative effects, calcitonin is known to diminish sensitivity to painful stimuli. The present study aimed to clarify whether calcitonin has similar effects on stimulus processing in other modalities. Effects of calcitonin were assessed on brain potentials recorded from the human scalp which were evoked either by auditory clicks or visual checkerboard pattern reversals. Twelve healthy men were tested in a double-blind intra-subject design receiving either 0.1 IU/kg salmon calcitonin (sCT) or 1.0 IU/kg sCT or saline solution during a 20 min IV infusion. sCT significantly increased latency of wave V of the brainstem auditory evoked potential (BAEP). Effects of BAEP wave V increased in magnitude with increasing dose of sCT and with decreasing intensity of the click stimulus. There was also a slight increase in latency of the N80 of the pattern-reversal visual evoked potential (PR-VEP). Additionally, subjects rated themselves as less activated following the high dose of sCT compared to placebo. The pattern of results is in accord with a slowing or inhibitory influence of calcitonin on auditory and visual sensory processing, thus paralleling findings concerning calcitonin effects on the perception of painful somatosensory stimuli. PMID- 1589562 TI - Effects of drugs of abuse on acquisition of behavioral chains in squirrel monkeys. AB - The acute effects of various drugs of abuse on the acquisition of chains of behavior were assessed in squirrel monkeys trained to respond on three keys for food. Each new session the monkeys acquired a different four-response chain by responding sequentially on three keys in the presence of four different stimuli. Incorrect responses inactivated the keys and darkened the chamber for 10 s (time out). Dose-effect curves were obtained by administering the drugs intramuscularly before the session and recording their effects on the rate and accuracy of responding. Cocaine, d-amphetamine, and delta 9-tetrahydrocannabinol all decreased the accuracy and rate of responding within the dose range of 0.56-3 mg/kg. The highest dose of morphine tested (3 mg/kg) produced parallel decreases in the accuracy and rate of responding in some monkeys but had no effect at lower doses. These drugs decreased within-session accuracy though clearly acquisition did occur, but high doses of caffeine (30 and 56 mg/kg) prevented acquisition and recovery of performance and, furthermore, at 30 mg/kg these effects were observed in the absence of decreases in the rate of responding. The drugs of abuse tested all produced dose-related decreases in both the accuracy and rate of responding, and the decreases in accuracy were primarily observed only at doses that also decreased response rates. Therefore, based on these results from nonhuman primates each of these drugs has the potential to alter learning particularly when doses that disrupt other behaviors are administered. PMID- 1589563 TI - Quantification of naturally occurring benzodiazepine-like substances in human breast milk. AB - The possible occurrence of benzodiazepine-like substances in human breast milk was investigated in 35 healthy, newly delivered women who were known not to be taking benzodiazepines. Maternal blood samples and a sample of breast milk were obtained on the fifth post partum day. A radioreceptor technique (lower limit of detection 1.5 ng/ml; difference between duplicates at various concentrations less than 7%) was used for measuring benzodiazepine-like substances in blood and breast milk (with and without prior extraction). No benzodiazepine-like substances could be demonstrated in any of the blood samples taken from the 35 women. Measurable concentrations of benzodiazepine-like substances were demonstrated in all but 1 of the 35 breast milk samples. The mean concentration of benzodiazepine-like substances for all 35 women was 4.3 +/- 2.3 ng/ml (range 0 9.3 ng/ml) expressed as lorazepam. The corresponding value for extracted breast milk was 2.6 +/- 1.5 ng/ml (range 0-7.0 ng/ml). There was no association between concentrations of benzodiazepine-like substances in breast milk and maternal age, weight, height and body mass or parity, or the sex of the infant and infant birth weight. We suggest that non-detectable amounts of benzodiazepine-like substances in serum are concentrated in the mammillary glands and excreted in a higher concentration in breast milk. It is less likely that the relevant benzodiazepines are produced in the mammillary glands. PMID- 1589564 TI - Effects of the putative dopamine autoreceptor antagonists (+)-AJ 76 and (+)-UH 232 on the discriminative stimulus properties of cocaine. AB - Recent evidence suggests that the putative dopamine (DA) autoreceptor antagonists, (+)-AJ 76 and (+)-UH 232, share some neurochemical and behavioral effects with both psychostimulants and neuroleptics. The ability of (+)-AJ 76 and (+)-UH 232 to mimic or antagonize the stimulus effects of cocaine was investigated in rats trained to discriminate 5 mg/kg (N = 8) or 10 mg/kg (N = 8) of cocaine from saline in a two-lever, water-reinforced, drug discrimination task. In the cocaine (10 mg/kg) group, administration of (+)-AJ 76 (2.5-20 mg/kg) engendered only a partial substitution for cocaine (maximum 60% cocaine-lever responses). Given in combination with cocaine (10 mg/kg), (+)-AJ 76 (2.5-40 mg/kg) did not significantly attenuate the cocaine cue. A fixed dose of (+)-AJ 76 (2.5 or 10 mg/kg) plus various doses of cocaine (1.25-5 mg/kg) did not alter the cocaine dose-response curve. (+)-UH 232 (2-16 mg/kg) produced primarily saline appropriate responding in rats trained to discriminate 5 mg/kg of cocaine and was unable to block the interoceptive cocaine state when given in combination with cocaine (5 mg/kg). (+)-UH 232 (2 or 8 mg/kg) also did not alter the cocaine dose response curve. These results suggest that (+)-AJ 76 and (+)-UH 232 elicit only weak or no cocaine-like stimulus effects and, unlike neuroleptics, do not attenuate the cocaine cue. PMID- 1589565 TI - Tolerance to the effects of ethanol on the speed and success of reaction time responding in the rat: effects of age and intoxicated practice. AB - An animal model of human reaction time (RT) was used to investigate the effects of age and intoxicated practice on the development of tolerance to the motor impairing effects of ethanol (EtOH). Young (8-9 month) and old (24-26 month) Fischer 344 rats were trained to release a lever in response to an auditory and visual stimulus in order to avoid mild footshock. The animals were divided into groups to receive either intoxicated (EtOH-before) or unintoxicated (EtOH-after) RT testing. Successful avoidance and response latencies were impaired in young and old rats after the initial exposure to EtOH (EtOH-before group). Tolerance developed to EtOH's effects on successful avoidance and on response latencies whether or not the rats received intoxicated RT practice; however, intoxicated practice facilitated tolerance development to EtOH's effects on successful avoidance but not on response latencies. While the initial sensitivity and the level of tolerance that developed to EtOH's effects were similar in young and old rats, the old rats were generally more sensitive to EtOH and developed tolerance at a slower rate. These results suggest that tolerance develops to the effects of EtOH on RT and that intoxicated practice can have different effects on the parameters of the behavioral response. PMID- 1589566 TI - Comparison of the daytime sleep and performance effects of zolpidem versus triazolam. AB - Fifty healthy male subjects were administered zolpidem (5, 10, or 20 mg), triazolam (0.5 mg) or placebo, then attempted to sleep in a non-sleep-conducive environment. Subjects were awakened at 90 min post-drug (near peak blood concentration for both drugs) and tested on several cognitive tasks, including Two Column Addition, Logical Reasoning, and a Simulated Escape Task. This was followed by a second, 3.5-h sleep period. Hypnotic efficacy of the 20 mg zolpidem (Z-20) dose was similar to that of the 0.5 mg triazolam (TRIAZ) dose, as indicated by comparably shortened sleep latencies and lengthened total sleep times. Though accuracy on most performance measures was not affected by either drug, a reduction in speed of responding on logical reasoning and addition tasks was evident for the TRIAZ group at 90 min post-drug (Ps less than 0.05). On the simulated escape task, only triazolam significantly increased the mean number of errors, and interfered with subsequent memory of the task. Thus, zolpidem had milder effects on performance than triazolam. However, 60% of the Z-20 subjects experienced mild, adverse physical reactions. Performance differences between somnogenically comparable doses of zolpidem and triazolam may be due to their differential affinities for the BZ1 and BZ2 receptor subtypes. PMID- 1589567 TI - Convulsive behaviour during alcohol dependence: discrimination between the role of intoxication and withdrawal. AB - Male Wistar rats were subjected to repeated weekly episodes of 2 days severe alcohol intoxication (intragastric intubation) and 5 days of withdrawal. In half of the animals the withdrawal reaction was attenuated during the first nine weekly episodes by intragastric intubations with phenobarbital. During episodes 10-14 both phenobarbital treated and phenobarbital untreated animals were allowed to develop a withdrawal reaction; all animals were video-recorded during withdrawal and the records were rated blindly for the occurrence of convulsive seizures. The results were analyzed by step-wise logistic analysis of regression including phenobarbital treatment, alcohol dose and intoxication score as explanatory variables for the occurrence of convulsive seizures. The animals that had been in withdrawal during all episodes developed significantly more convulsive seizures compared with animals that had their first nine withdrawal episodes attenuated by phenobarbital. The development of withdrawal seizures depended on repeated episodes of withdrawal, whereas repeated alcohol intoxication per se did not explain the development of seizures. There were no differences between the groups in the severity of the non-convulsive signs of alcohol withdrawal. Thus the development of seizures and the non-convulsive signs of alcohol withdrawal may result from two pathogenetically different mechanisms: 1) seizures from a cumulative kindling-like effect over long time periods and 2) physical signs of alcohol withdrawal may reflect the degree of physical dependence during the most recent drinking bout. PMID- 1589568 TI - Two-dimensional crystallization of membrane proteins. PMID- 1589569 TI - Linear dichroism spectroscopy of nucleic acids. PMID- 1589570 TI - Radiation chemical studies of sensitization by 5-bromouridine-5'-monophosphate (5 BrUMP). AB - This study was undertaken to investigate the mechanism of chemical radiosensitization by halogenated bases incorporated into DNA. Radiation-induced base and sugar-phosphate backbone damage to 5-bromouridine-5'-monophosphate (5 BrUMP) was monitored using a flow system connected in series with a recording spectrophotometer, a bromide (Br-)-specific ion analyzer and a Technicon auto sampler. The system was used to assay loss of UV-absorbing 5,6 double-bond, release of Br- and inorganic phosphate (Pi) release using an automated colorimetric method, as a function of gamma-ray dose. Results obtained with radical scavengers indicate that, unlike non-halogenated nucleotides where the hydroxyl radical (.OH) is the principal damaging species, 5-BrUMP is damaged by the hydrated electron (e-aq), hydrogen atom (H.) and .OH, producing a high yield of base damage and Br- and Pi release in anoxia. Another novel feature of 5-BrUMP radiolysis is that oxygen, by converting e-aq and H. to the unreactive superoxide radical anion (O2-), has a protective effect on both base and phosphate ester damage. Under .OH-scavenging conditions, where the radiation yield of reductive debromination is 3.8, there is some Pi release, suggesting the possibility of intramolecular hydrogen atom transfer from the sugar ring to the 5-uracilyl radical and subsequent sugar-phosphate bond cleavage. This hypothesis is supported by the action of oxygen and thiols in modifying the e-aq-mediated sugar phosphate damage. PMID- 1589572 TI - Magnetic field exposure of marrow donor mice can increase the number of spleen colonies (CFU-S 7d) in marrow recipient mice. AB - Transplantation of bone marrow cells of magnetic-field-exposed mice led to increased numbers of spleen colonies (CFU-S 7d) in conditioned recipient mice (Peterson et al. 1986). Here we report on the dependence of this phenomenon on body temperature, field strength and exposure time. It was found that the effect can only be seen when the body temperature is 27 degrees C, the field strength not less than 1.4 T and the exposure time at least 15 min. It is suggested that the magnetic field increases the number of spleen colonies either directly by affecting membrane components (receptors) responsible for the seeding of the transplanted stem cells to the recipient spleens or indirectly affecting radical/redox-systems that may have a regulatory function in the stem cells. PMID- 1589571 TI - Prenatal pathogenesis of hydro-micrencephaly induced by X-rays. An animal model. AB - Experimental results are presented which describe induction and pathogenesis of the hydro-micrencephaly in NMRI-mice after single X-irradiation with 0.9 Gy or 1.9 Gy on gestation day (gd) 12. The ultrastructural alterations in the ventricular walls are sequentially investigated up to gross developmental damage. The ventricular zone is the most sensitive region in the developing brain. Its constituting undifferentiated and proliferating cells lose their palisade like orientation and fail subsequently to differentiate into primitive neurons, glia cells, or ependymal cells. Structurally this results in the thinning of ventricular walls by more than 50% associated with periventricular oedema and a dilation of the brain ventricles by 20-60%. Damage is clearly more pronounced with the higher dose. Repair processes originate from regions with intact Zonulae adherents which give also rise to typical globular or cylindrical heterotopic structures; these are known as rosettes and made up from undifferentiated proliferating ventricular cells. Perinatally in these rosettes cell replication persists, at a time when cell production in the ventricular zone has ceased. Histological changes are most prominent in and around the telencephalic roof consisting in replacement of the ependymal lining by a felt of glial fibers, faulty myelinisation, and periventricular oedema; postnatally these structural alterations lead to hydro-micrencephaly. Results from this animal model can be translated to the human situation because the fundamental developmental processes in the brain of mammals are similar despite species related differences of the time scale. PMID- 1589573 TI - Uptake and transfer factors of 137Cs by mushrooms. AB - The 137Cs content of 118 species (668 samples) of higher fungi collected in the period from August 1984 to October 1989 at three different locations in Styria, Austria, was determined by gamma-spectrometry. The Cs-content of most mushrooms has been increasing since September 1986. In order to find out which factors determine the 137Cs-contamination of mushrooms and the transfer-value soil to mushroom, the concentration of total and plant-available radiocesium in soils as well as the pH-value, the content of humus, clay, silt, sand, exchangeable cations, the composition of the clay minerals, and the particle size distribution of the soils of two different locations were examined. The higher the 137Cs contamination of the soil, the thicker the layer of humus and the higher the content of humus, the lower the pH-value, and the lower the amount of essential cations, especially of K+, the higher the amount of 137Cs plant-available will be. Therefore, the contamination of the mushrooms in the coniferous forest of Koralpenblick (1000 m) is higher than in the mixed forest at the Rosenberg around Graz at approx. 500 m height. Of 26 different species of mushrooms measured at both sites, only 61% show the highest TF-values soil to mushrooms also at the Koralpenblick. In the spruce forest at Koralpenblick there are many species of mushrooms with high 137Cs-contamination which were not found at the Rosenberg. However, the properties of the species to which a mushroom belongs are more important than environmental conditions and soil properties. The transfer values of 40K stay within narrow bounds, whereas those of 137Cs differ widely. PMID- 1589574 TI - Increase of the chlorophyll fluorescence ratio F690/F735 during the autumnal chlorophyll breakdown. AB - The chlorophyll content and the fluorescence induction kinetics at two wavelengths (690 nm and 735 nm) have been measured in leaves of nine common broadleaf tree species during the autumnal chlorophyll breakdown. The ratio of the chlorophyll fluorescence maxima F690/F735 was determined at fluorescence maximum (fm) and at steady-state conditions (fs) by the laser-induced fluorescence emission using the two-wavelength fluorometer. The ratio F690/F735 increases with the leaf discolouring during the autumnal chlorophyll breakdown. The relationship between the chlorophyll content and the ratio F690/F735 can be expressed by a power function (curvilinear relationship) which is valid for all the species examined. In most cases the ratio F690/F735 measured in the upper leaf side is lower than that in the lower leaf side, but the trend is the same along the decreasing chlorophyll content. The ratio F690/F735 is always higher at maximum fluorescence than at steady-state fluorescence in the upper as well as lower leaf side and these values are well fitted in a linear correlation. This study confirms the usefulness of the ratio F690/F735 as a suitable non destructive indicator of the in-vivo chlorophyll content, especially at medium and low chlorophyll content. PMID- 1589575 TI - Time-resolving luminescence techniques for possible detection of forest decline. I. Long term delayed luminescence. AB - Needles from spruces at different environmental and physiological conditions were analyzed by long term delayed luminescence in the seconds-range (LDL) using a novel set-up with on-line computer and a specially written computer program. Upon red light induction, the LDL-kinetics showed a super-position of three exponentially decaying components ("fast", "medium" and "slow") with reaction constants of kf = 5-15 s-1, km = 0.8-1.8 s-1 and ks = 0.13-0.23 s-1, ks-values are fairly independent of the individual tree and quite stable throughout the whole year. They are also independent of the status and localization, i.e. the physiological situation of the individual tree. However, km- and kf-values as well as the related amplitudes Am and Af exhibit a general, significant seasonal variation and obviously are correlated with the damage class or the environmental situation of the individual tree. Therefore, the measurement of long term delayed luminescence might offer a valuable piece of information in search of an early detection of forest decline. PMID- 1589576 TI - Time-resolving luminescence techniques for possible detection of forest decline. II. Picosecond chlorophyll fluorescence. AB - Needles from spruces at different environmental and physiological conditions were analyzed by picosecond fluorescence spectroscopy using a novel laser diode and single photon counting detection. The decay curves of chlorophyll fluorescence showed a superposition of three exponentially decaying components with time constants of T1 = 100-200 ps, T2 = 300-500 ps and T3 = 2.0-3.5 ns. A high relative intensity of the long-lived component was found in damaged spruces as well as in trees showing first symptoms of yellowing, needle loss or parasite infection, although all measurements were carried out with green needles which appeared visually intact. Therefore, fluorescence spectroscopy with subnanosecond time resolution seems to be a valuable attempt for an early detection of forest decline. PMID- 1589577 TI - Ventromedial hypothalamic neurons in the mediation of long-lasting effects of estrogen on lordosis behavior. PMID- 1589579 TI - Cerebrovascular innervation of small bats. PMID- 1589578 TI - Release of GABA and taurine from brain slices. AB - In brain slices the mechanisms of release of GABA have been extensively studied, but those of taurine markedly less. The knowledge acquired from studies on GABA is, nevertheless, still fragmentary, not to speak of that obtained from the few studies on taurine, and firm conclusions are difficult, even impossible, to draw. This is mainly due to methodological matters, such as the diversity and pitfalls of the techniques applied. Brain slices are relatively easy to prepare and they represent a preparation that may most closely reflect relations prevailing in vivo, since the tissue structure and cellular integrity are largely preserved. In our opinion the most recommendable method at present is to superfuse freely floating agitated slices in continuously oxygenated medium. Taurine is metabolically rather inert in the brain, whereas the metabolism of GABA must be taken into account in all release studies. The use of inhibitors of GABA catabolism is discouraged, however, since a block in GABA metabolism may distort relations between different releasable pools of GABA in tissue. It is not known for sure how well, and homogeneously, incubation of slices with radioactive taurine labels the releasable pools but at least in the case of GABA there may prevail differences in the behavior of labeled and endogenous GABA. It is suggested therefore that the results obtained with radioactive GABA or taurine should be frequently checked and confirmed by analyzing the release of respective endogenous compounds. The spontaneous efflux of both GABA and taurine from brain slices is very slow. The magnitude of stimulation of GABA release by homoexchange is greater than that of taurine under the same experimental conditions. However, the release of both amino acids is generally enhanced by a great number of structural analogs, the most potent being those which are simultaneously the most potent inhibitors of uptake. This may result in part from inhibition of reuptake of amino acid molecules released from slices but the findings may also signify that the efflux of GABA and taurine is at least partially mediated by the membrane carriers operating in an outward direction. It is thus advisable not to interpret that stimulation of release in the presence of uptake inhibitors solely results from the block of reuptake of exocytotically released molecules, since changes in the carrier-mediated transport are also likely to occur upon stimulation. The electrical and K+ stimulation evoke the release of both GABA and taurine. The evoked release of GABA is several-fold greater than that of taurine in slices from the adult brain.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1589580 TI - Patterns of spread of different demyelinating processes in the myelin sheath. PMID- 1589581 TI - Gene expression in cells of the central nervous system. AB - This review summarized a part of our studies over a long period of time, relating them to the literature on the same topics. We aimed our research toward an understanding of the genetic origin of brain specific proteins, identified by B. W. Moore and of the high complexity of the nucleotide sequence of brain mRNA, originally investigated by W. E. Hahn, but have not completely achieved the projected goal. According to our studies, the reason for the high complexity in the RNA of brain nuclei might be the high complexity in neuronal nuclear RNA as described in the Introduction. Although one possible explanation is that it results from the summation of RNA complexities of several neuronal types, our saturation hybridization study with RNA from the isolated nuclei of granule cells showed an equally high sequence complexity as that of brain. It is likely that this type of neuron also contains numerous rare proteins and peptides, perhaps as many as 20,000 species which were not detectable even by two-dimensional PAGE. I was possible to gain insight into the reasons for the high sequence complexity of brain RNA by cloning the cDNA and genomic DNA of the brain-specific proteins as described in the previous sections. These data provided evidence for the long 3' noncoding regions in the cDNA of the brain-specific proteins which caused the mRNA of brain to be larger than that from other tissues. During isolation of such large mRNAs, a molecule might be split into a 3'-poly(A)+RNA and 5'-poly(A)-RNA. In the studies on genomic DNA, genes with multiple transcription initiation sites were found in brain, such as CCK, CNP and MAG, in addition to NSE which was a housekeeping gene, and this may contribute to the high sequence complexity of brain RNA. Our studies also indicated the presence of genes with alternative splicing in brain, such as those for CNP, MAG and NGF, suggesting a further basis for greater RNA nucleotide sequence complexity. It is noteworthy that alternative splicing of the genes for MBP and PLP also produced multiple mRNAs. Such a mechanism may be a general characteristic of the genes for the myelin-specific proteins produced by oligodendrocytes. In considering the high nucleotide sequence complexity, it is interesting that MAG and S-100 beta genes etc. possess two additional sites for poly(A).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1589582 TI - Oxidative damage and cerebral aging. PMID- 1589583 TI - Anatomy and connectivity of intrastriatal striatal transplants. PMID- 1589584 TI - Cell death and removal in the cerebral cortex during development. PMID- 1589585 TI - Principles of organization of neural systems controlling automatic movements in animals. PMID- 1589586 TI - Early findings from a pharmacokinetically designed double-blind and placebo controlled study of lithium for adolescents comorbid with bipolar and substance dependency disorders. AB - 1. This manuscript reports the early findings from a National Institute on Drug Abuse funded study of lithium for adolescents dually diagnosed with bipolar and substance dependency disorders. The authors elected to publish early findings in the hope that it would accomplish a twofold mission. 2. The first part would be to encourage other investigators to participate in research in this area and the second would be to heighten the awareness of clinicians that adolescents presenting with either one of these disorders might also have the other. 3. The early findings demonstrated the feasibility of recruiting, retaining and monitoring this complex population on an outpatient basis. 4. Steady-state serum lithium levels were pharmacokinetically placed in the study range, 0.9-1.3 mEq/L. Preliminary results are encouraging in finding lithium more effective than placebo for alleviating both the substance dependency and the mood disordered symptomatology. 5. The characteristics of the study population to date have been chronicity of both disorders, impairment in the severe range in multiple areas of functioning, and strong family histories for both affective and substance use disorders. The substance dependency was to both alcohol and marijuana; but all subjects also had marked polydrug abuse. 6. In order to best monitor lithium compliance and drug/alcohol use during protocol, randomly timed weekly serum and urine assays were obtained. 7. The implications of these early findings for the outcome of this acute phase study and for the development of longitudinal treatment strategies are discussed. PMID- 1589587 TI - Nortriptyline response in elderly depressed patients. AB - 1. Depressed geriatric patients were treated with nortriptyline (NT) for 6 weeks. The authors measured serum levels of NT and 10-hydroxynortriptyline (10-OH-NT) using a column-switching HPLC method, and examined aging effects on NT steady state levels to NT doses (doses/kg) ratios and NT levels to 10-OH-NT levels ratios as well as clinical response and propensity for side effects. 2. There was no significant relationship between the ages and the NT serum levels to NT doses (doses/kg) ratios, the ages and the 10-OH-NT levels to NT levels ratios, or the ages and the clinical response or the %improvement of Hamilton Scores. 3. Then the authors divided the subjects into two groups: a younger group and an elderly group with the cut off age of 60. The elderly group received significantly smaller doses of NT and had significantly lower serum levels of NT. The elderly group had tendency to have lower serum levels of 10-OH-NT. However, no significant difference was found in the improvement scores or the %improvement of depression. The elderly patients did not have higher propensity for unnegligible side effects. PMID- 1589588 TI - Sleep, age, depression and the cholinergic REM induction test with RS 86. AB - 1. Healthy volunteers and patients with a major depressive disorders were administered 1.5 mg RS 86 (a cholinergic agonist) and placebo in a randomized double-blind cross-over design at 10 p.m. prior to bedtime. 2. Polysomnographic recordings demonstrated a significantly more pronounced shortening of REM latency after cholinergic stimulation in depressed patients compared to healthy subjects. 3. Even those depressed patients displaying placebo REM latencies in the normal range showed sleep onset REM periods after cholinergic stimulation. 4. The results support the reciprocal interaction model of NonREM-REM sleep regulation and the cholinergic-aminergic imbalance model of depression. PMID- 1589589 TI - Change in the cytoskeletal system in fibroblasts from patients with familial Alzheimer's disease. AB - 1. Fibroblasts were cultured from four patients, two patients from two independent family lines, clinically diagnosed as familial Alzheimer's disease. 2. Adhesion efficiency to the dish was significantly suppressed with fibroblasts from patients with familial Alzheimer's disease compared with the cells from the age-matched control. 3. Cytoskeletal systems were visualized by immunofluorescent staining with antibodies against tubulin, actin, and vimentin, showing unique dearrangement of vimentin fibers in fibroblasts from familial Alzheimer's disease. 4. Regrowth of vimentin fibers after colchicine treatment was slower with fibroblasts from familial Alzheimer's disease than that of the control. 5. Western blotting analysis showed no change in tubulin, actin, and vimentin, but the size of fodrin in familial Alzheimer fibroblasts were different from that of the control cell. PMID- 1589590 TI - Postnatal development of parvalbumin immunoreactivity in axon terminals of basket and chandelier neurons in monkey neocortex. AB - 1. Two classes of GABAergic inhibitory interneurons, chandelier and basket cells, are known regulators of pyramidal neurons. Parvalbumin (PV) a calcium binding protein, has been shown to be a marker for axon terminals of subpopulations of these interneurons. 2. Immunohistochemical methods were used in this study to examine changes in the distribution of PV-immunoreactive (IR) chandelier and basket axon terminals during postnatal development of monkey neocortex. 3. Our results indicate a differential effect of postnatal development on PV-IR axon terminals of chandelier and basket neurons that is region-specific. 4. The differential regional, laminar and developmental pattern of PV-IR axon terminals of chandelier and basket cells may provide insight into the functional role of these classes of inhibitory neurons in primate neocortex. PMID- 1589591 TI - Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes. AB - 1. A possible coupling of the rat cerebral cortex 5-hydroxytryptamine (5HT)-1A receptors to isletactivating protein (IAP, pertussis toxin) sensitive Gi protein was investigated by studying the effects of a guanosine 5'-triphosphate (GTP) and IAP injection to the rat ventricle. 2. Scatchard analysis showed that Bmax value of the high-affinity componentin [3H]8-hydroxy-2-(di-n-propylamino) tetralin (8 OH-DPAT) binding was decreased by pretreatment with IAP. 3. GTP caused a significant decreased Bmax of the high affinity site for [3H]8-OH-DPAT binding. It was noted that the IAP suppressed the cyclic AMP production by 5HT, VIP and Forskolin. 4. These results suggest that the rat cortex 5HT-1A receptors are linked to the Gi protein. 5. After 3 weeks chronic administration of amitriptyline (5mg/kg), desipramine (5mg/kg), imipramine (5mg/kg), doxepin (5mg/kg) and trazodone (10mg/kg), the receptor binding assay was carried out on 5HT-1A receptors. 6. It was observed that all the antidepressant drugs except for imipramine increased the number of high-affinity sites of the 5HT-1A receptors in the frontal cortex. 7. These results suggested that the increase of the Bmax for the 5HT-1A receptor might be related to the effectiveness of the antidepressant drugs. PMID- 1589592 TI - Behavioral tolerance to one effect of the serotonergic agonist TFMPP. AB - 1. In mice isolated for one week and observed in pairs with non-isolated mice under a reversed beaker, the serotonergic agonist: 1-3 (trifluoromethyl)phenylpiperazine (TFMPP) increased the number of escape attempts. 2. A partial tolerance to this effect has been observed in mice which were tested a first time after administration of TFMPP one week sooner. 3. An analysis of this form of tolerance was carried out by changing successively and separately each of the events concomitant of this tolerance. 4. The results show that this tolerance is not a pharmacocinetic or a pharmacodynamic one. Observation of the tolerance required the performance of the first test in a drug state. The more likely explanation is that this tolerance results from a conditioned opponent response. PMID- 1589593 TI - Aspects of animal experiments for evaluation of cognitive enhancers: in particular, the behavioral characteristics of Mongolian gerbils. AB - 1. The step-through passive avoidance response and discrete lever-press avoidance response of Mongolian gerbils were evaluated to point out the basic problems in the learning and memory tests in this species. 2. Mongolian gerbils exhibited extremely poor acquisition and maintenance of the passive avoidance response. 3. In contrast to the result under the passive avoidance situation, Mongolian gerbils demonstrated an excellent performance under the discrete lever-press avoidance situation. 4. A 5-min brain ischemia elicited a severe morphological damage of the pyramidal cells in hippocampal CA1 region. 5. A small part of such ischemic animals showed a deficit of acquisition of the discrete lever-press avoidance. 6. These results suggest that there is merit and demerit of the acquisition dependent on the type of tasks, and that the brain function of Mongolian gerbils may be maintained even after the ischemic operation. PMID- 1589594 TI - Association of functional alteration in intracellular signal transduction systems with the occurrence of up-regulation of muscarinic receptors in primary cultured neurons. AB - 1. Alterations in intracellular biosignaling systems associated with the up regulated muscarinic receptor were investigated using primary cultured neurons exposured to 10 nM atropine for 5 days. 2. In neurons treated with atropine, the response of PI turnover to muscarinic stimulation decreased in comparison with that in non-treated neurons. 3. The GTP gamma S-stimulated PI turnover also reduced in neurons possessing up-regulated muscarinic receptor, although phospholipase C activity was not different in these two types of neurons. 4. In addition, the long-term exposure (5 days) to atropine induced the increase in GTPase activity and [3H]GppNHp binding. 5. These results suggest that the decreased response of PI turnover to muscarinic stimulation may be attributed to the functional deterioration of G-protein itself and/or coupling between G protein and phospholipase C. 6. The present results also strongly suggest that the accentuation of the function of G protein may occur in association with the up-regulation of muscarinic receptor. PMID- 1589595 TI - Pituitary adenylate cyclase activating polypeptide-27 (PACAP-27) inhibits pentagastrin-stimulated gastric acid secretion in conscious rats. AB - Pituitary adenylate cyclase activating polypeptide (PACAP) is a novel neuropeptide and has two amidated forms, PACAP-27 and PACAP-38. Its chemical structure is similar to that of vasoactive intestinal peptide (VIP). In our previous studies, we found that PACAP has a stimulatory effect on rat exocrine pancreas secretion and an inhibitory effect on rat gastrointestinal motility. These effects of PACAP-27 were greater than those of PACAP-38 and VIP. In the present study, we examined the effect of PACAP-27 on basal and pentagastrin (PG) stimulated gastric acid secretion in conscious rats and compared its effect with that of VIP. Rats were equipped with a chronic gastric fistula and a permanent IV line and separately housed in metabolic cages. The effects of PACAP-27 and VIP at doses of 1.25, 2.5, 5 and 10 nmol/kg/h on basal and PG (24 micrograms/kg/h) stimulated gastric acid secretion were tested. Our results showed that: (1) VIP had no significant effect on basal and PG-stimulated gastric acid secretion at the tested doses. (2) PACAP-27 had no effect on basal acid secretion but had a dose-dependent inhibitory effect on PG-stimulated gastric acid secretion. The highest inhibition by PACAP-27, 68.2 + 8.1%, was achieved at 5 nmol/kg/h. We suggest that PACAP may have a regulatory role in gastric acid secretion. PMID- 1589596 TI - Abnormalities of the thyroid hormone negative feedback regulation of TSH secretion in spontaneously hypertensive rats. AB - Spontaneously hypertensive rats (SHR) are characterized by several neuroendocrine abnormalities including a chronic hypersecretion of thyrotropin (TSH) of unknown etiology. We hypothesized that the inappropriately high TSH secretion in SHR may be the result of an impaired thyroid hormone negative feedback regulation of hypothalamic thyrotropin-releasing hormone (TRH) and/or pituitary TSH production. To test this hypothesis, SHR or their normotensive Wistar-Kyoto (WKY) controls were treated with either methimazole (0.02% in drinking water) to induce hypothyroidism or administered L-thyroxine (T4) at a dose of 0.8 or 2.0 micrograms/100 g body weight/day to induce hyperthyroidism. All treatments were continued for 14 days after which animals were killed under low stress conditions. TSH concentrations in plasma and anterior pituitary tissue were 2 fold higher (P less than 0.01) in euthyroid SHR compared to WKY control rats while thyroid hormone (T3 and T4) levels were in the normal range. Hypothyroidism induced by either methimazole or thyroidectomy caused a significant (P less than 0.01) rise of plasma TSH levels in both WKY and SHR rats. However, relative to the TSH concentrations in control animals, the increase of plasma TSH in SHR was significantly blunted (P less than 0.01) in comparison to the WKY group. Hypothyroidism caused a significant depletion of TRH in stalk-median eminence (SME) tissue in both groups of rats. However, no differences between SHR and WKY rats were observed. The administration of thyroid hormone caused a dose dependent suppression of plasma TSH levels in both strains of rats. However, at both doses tested plasma TSH concentrations in SHR rats were significantly less suppressed (P less than 0.05) than those in WKY animals. Under in vitro conditions basal and potassium induced TRH release from SMEs derived from SHR was significantly (P less than 0.05) higher than that from WKY rats, whether expressed in absolute terms or as percent of content. These findings suggest that the thyroid hormone negative feedback regulation of TSH secretion may be impaired in SHR rats. Our data do not allow conclusions as to whether defects in the regulation of TSH production are located exclusively at the hypothalamic level. Since the overproduction of hypothalamic TRH and hypophysial TSH should lead to an increased thyroid hormone biosynthesis other defects in the hypothalamus pituitary-thyroid-axis may contribute to the abnormal regulation of TSH secretion in SHR rats. PMID- 1589597 TI - Alcohol and cocaine. Similarities and differences. PMID- 1589598 TI - Prohibition or liberalization of alcohol and drugs? A sociocultural perspective. AB - The "war against drugs," and calls for increasing restrictions on the availability of alcoholic beverages, reflect a resurgence in the popularity of mandated formal controls and suspicion of informal controls. A small, but increasing countercurrent recommends various forms of liberalization of access to alcohol and drugs. Both viewpoints are being promulgated for their efficacy in reducing and/or preventing a broad range of problems "associated with" (and often assumed to be caused by) psychoactive substances. In the absence of rigorous empirical evidence on the subject, critical examination of prior experience in the United States, and of analogous experiences in other cultures, provides a range of relevant "natural experiments." The association of alcohol and cocaine with various problems varies markedly from culture to culture and from time to time within a single culture. The definition of "abuse" problems is evidently based on social constructions rather than reflecting the epidemiology of public health and social welfare. Formal and informal controls are not mutually exclusive and can be complementary. A broader view of education and of controls could result in fruitful natural experiments among jurisdictions within this country, and lessen alcohol and drug problems at the same time. PMID- 1589599 TI - A comparison of drug conditioning and craving for alcohol and cocaine. AB - Craving is a potentially important concept that is difficult to define and study in the laboratory. Although alcohol and cocaine are very different pharmacologically, this discussion emphasizes common factors in addiction to these drugs, such as the tendency of alcoholics and cocaine abusers to crave these substances. I review commonalities in drug conditioning and cue reactivity to alcohol and cocaine. Both drugs support Pavlovian conditioning when they are presented as unconditioned stimuli, whether studied in rodents or humans. In addition, both drugs are craved when abusers are presented with stimuli associated with these drugs. Finally, I propose a theoretical definition of craving based on autoshaping and sign-tracking phenomena that suggests a common mechanism of addiction to these drugs. This model defines craving as a reflection of sign tracking to internal and external stimuli that have in the past reliably predicted presentation of these drugs. PMID- 1589600 TI - Psychotherapy and patient needs in the treatment of alcohol and cocaine abuse. AB - The effectiveness of psychotherapy in the treatment of substance abuse continues to be debated among theorists and practitioners. This paper proposes that psychotherapy can play an important role in the treatment of the addictions. However, it is critical that this psychotherapy is geared toward the special needs of substance abusers. Using research on the process of change as a guide, a psychotherapeutic approach for substance abusers is described that responds to the needs of the individual as they shift during the different phases of recovery. Contemporary adaptations of psychodynamic psychotherapy are recommended, along with the appropriate cognitive-behavioral and self-help approaches. In addition, the different clinical considerations for alcohol versus cocaine abusers are examined as they evolve during the change process. PMID- 1589601 TI - Acute treatment of alcohol and cocaine emergencies. AB - This chapter addresses the acute treatment of alcohol and cocaine. Because of the widespread use of both these drugs, health professionals must recognize the medical complications of alcohol and cocaine abuse and addiction. The biochemistry will be briefly reviewed as an avenue to understand the different treatment targets and modalities. PMID- 1589602 TI - Clinical pathology. Overview. PMID- 1589603 TI - Developing and evaluating new treatments for alcoholism and cocaine dependence. AB - Progress in the treatment of any disorder requires the development of methods for evaluation as well as the development of potentially effective new treatments. In this chapter we briefly describe a new instrument to be used in the measurement of substance abuse treatment, the Treatment Services Review. Some of the potential problems in evaluation research are discussed, such as the tendency for more severely ill patients to be more willing to give up their right to choose treatment and agree to randomization. These unexpected tendencies in study volunteers limit the generalizability of treatment research. Evaluation techniques are illustrated by two studies comparing inpatient and outpatient rehabilitation. The results for both alcohol dependence and cocaine dependence were positive, but there was no evidence of a significant advantage for one treatment environment over the other. This has important implications for program funding. We also describe our search for a new treatment technique based on a conditioning model for cocaine dependence. Pilot studies suggested an improvement in treatment outcome for the patients receiving the experimental treatment, and therefore, a prospective study with random assignment was conducted. PMID- 1589604 TI - Gastrointestinal complications of cocaine abuse. AB - The mechanisms thought to be responsible for cocaine-associated gastrointestinal injury are presented. In addition, the literature available concerning the enteric consequences of cocaine use is reviewed. PMID- 1589605 TI - Hepatotoxicity associated with cocaine abuse. AB - The mechanisms evaluated in animals as being responsible for cocaine associated hepatotoxicity are presented. The importance of the P-450 enzyme system in cocaine associated hepatotoxicity is emphasized. Moreover, the putative critical role of free radicals in such injury is discussed. Finally, the growing literature on clinical cases of cocaine hepatotoxicity is reviewed. PMID- 1589606 TI - Cardiovascular complications of cocaine abuse. AB - Cardiovascular complications are among the most common and dangerous complications of cocaine abuse, ranging from episodic arrhythmias to myocardial infarction, strokes, cardiomyopathy, and sudden death. The central nervous system mediated action of cocaine triggers an increase in circulating catecholamines, resulting in arterial vasoconstriction, increase in myocardial oxygen demand, myocardial ischemia, tachycardia, and other arrhythmias. The peripheral cardiovascular action of cocaine involves the inhibition of reuptake of catecholamines at adrenergic nerve terminals, with local release of epinephrine, direct stimulation and vasospasm of the coronary arteries, coronary intimal hyperplasia, inhibition of baroreceptors, interference with the electrical conduction through the myocardium, and direct myocardial toxicity. The cardiovascular complications of cocaine include cardiac dysrhythmias and hypertension, acute myocardial infarction, myocarditis, infectious endocarditis, ventricular dysfunction, dilated cardiomyopathy, hypotensive shock, and cerebral strokes. Cocaine-related vascular changes in the pregnant woman and fetus have been related to an increased incidence of abortion, abruptio placentae, and congenital anomalies of the fetus. PMID- 1589607 TI - Respiratory complications of cocaine abuse. AB - Upper respiratory and pulmonary complications of cocaine addiction have been increasingly reported in recent years, with most of the patients being intravenous addicts, users of freebase, or smokers of "crack." The toxicity of cocaine is complex and is exerted via multiple central and peripheral pathways. Recurrent snorting of cocaine may result in ischemia, necrosis, and infections of the nasal mucosa, sinuses, and adjacent structures. Pulmonary complications of cocaine toxicity include pulmonary edema, pulmonary hemorrhages, pulmonary barotrauma, foreign body granulomas, cocaine related pulmonary infection, obliterative bronchiolitis, asthma, and persistent gas-exchange abnormalities. Respiratory manifestations are nonspecific and include shortness of breath, cough, wheezing, hemoptysis, and chest pains. Severe respiratory difficulties have been reported in neonates of abusing mothers. In the absence of a cocaine abuse history, it may be difficult to recognize the etiological role of cocaine, especially in the absence of needle tracks pointing to previous intravenous drug abuse and/or negative toxicology. PMID- 1589608 TI - Emergency room evaluation of cocaine-associated neuropsychiatric disorders. AB - The widespread abuse of cocaine has produced an alarming number of cocaine related emergency room visits in the last several years. The authors discuss the various issues involved in emergency rom evaluation of patients who abuse cocaine and manifest signs and symptoms suggesting neuropsychiatric disease. Appropriate triage is emphasized, and a discussion of impediments to the accurate assessment of these patients ensues. The unique features of cocaine-induced mood, psychotic, and organic disorders are then detailed and contrasted with other functional and organic disorders. Strategies for the emergency room treatment of patients exhibiting symptomatology consistent with cocaine intoxication and withdrawal are outlined. The issues of psychiatric comorbidity and dual diagnosis in the cocaine abusing population are examined. In addition, the neurological complications associated with the use of cocaine are reviewed. Finally, emerging data from single photon emission computerized tomography (SPECT) analysis of cocaine abusers is reported. PMID- 1589609 TI - Dual-diagnosis empirical and developmental-humanistic approaches. AB - The association between alcohol and/or drug dependence and major psychiatric conditions such as schizophrenia has received increased attention from the professional community. Terms such as "dual diagnosis" used to designate these clinical occurrences have become common, reflecting the interest mentioned. This chapter reviews the prevalence of the association between substance abuse and psychiatric disorder, the nature of the interactions observed, and some of the implications for patient care and health policy. Following this empirical perspective, we present a developmental-humanistic approach that has been used in the psychotherapeutic management of these problems. Our review of information on dual diagnosis suggests that the association between the two processes--substance abuse and psychiatric disorder--is not fortuitous or just the result of environmental conditions. There are complex physiopathological links at the neurobiological level that deserve research attention. PMID- 1589610 TI - [The cerebrovascular stroke. Something that can be prevented]. PMID- 1589611 TI - [An epidemiological study of the distinct histological types of cutaneous melanoma in relation to other variables of the disease]. AB - A retrospective descriptive study is carried out from the whole of malignant cutaneous melanomas diagnosed at the Dermatology Service of the General University Hospital of Valencia (HGUV), during the period 1977-1987, in which the 80% of the whole of the cases in the province of Valencia are diagnosed, specifically 247 patients are studied. The ones located on the leg stand out 21%, followed by posterior thorax 14% and face 12%. Likewise, differences statistically significant p less than 0.001 are observed among the distinct histological types of cutaneous malignant melanoma (CMM) with regard to the depth of the tumours invasion (measured in Clark levels and millimetres of depth), mitosis/area, mitosis index and prognosis index. Being the lentigo of malignant melanoma (LMM) the histological type diagnosed in earlier phases, hence it is the most capable variant of curative treatment, just the opposite that happens to the nodular malignant melanoma (NMM), that is normally diagnosed in more advanced phases of the illness. PMID- 1589612 TI - [The importance of computerized axial tomography in the etiological diagnosis of Addison's disease]. AB - Sixteen cases of newly diagnosed Addison disease were studied by CT scan. An initial diagnosis was performed according to the clinical data of each patient, and a second diagnosis after examining the abdominal CT scan. According to the second diagnosis there were six patients with primary adrenal failure of probable autoimmune origin, six tuberculosis, two metastatic, one undetermined and one hemorrhagic. The second diagnosis coincided with the first one in 10 cases (62.5%), but was different in six cases (37.5%). Information obtained by CT scan modified the therapeutic attitude in 4 cases (25%). The main morphologic patterns of adrenal glands in CT scan (atrophy, calcification and enlargement) are commented as well as the importance of CT scan in the study of the more common etiologies of Addison's disease (tuberculosis, autoimmune, neoplastic metastasis and hemorrhage). It is concluded that the information obtained by CT scan is important in the etiological diagnosis of Addison disease and it is advised to perform it in all newly diagnosed cases. PMID- 1589613 TI - [The hormonal changes in postmenopausal women with rheumatoid arthritis]. AB - We have studied the levels of sexual hormones in 45 female patients suffering seropositive rheumatoid arthritis (RA). Patients were classified in two groups. Group 1 (premenopausal), was formed by 26 women and group 11 (postmenopausal) by 19 women. They were compared to 40 control women (20 premenopausal and 20 postmenopausal). Age and body surface as similar in both groups. Mean estradiol, progesterone and androgen plasma levels in group 1 were similar to the premenopausal control group. On the contrary, group 11 patients presented a statistically significant increase in plasma androgen levels when compared to the postmenopausal control group. This seems to indicate that postmenopausal women suffering rheumatoid arthritis present a hyperandrogenic situation, which could have a beneficial effect on the clinical expression of the disease. PMID- 1589614 TI - [Kluyvera ascorbata infections. Apropos 2 cases]. PMID- 1589615 TI - [Human genital myiasis due to Sarcophaga]. AB - Human myiasis are infestations produced by fly larvae which invade human tissues or cavities. We report a case of semi-specific myiasis which consisted in infestation of the vulvar region of an eighty-six-year old, diabetic patient who was admitted in a clinical center for elderly. The development from larva to adult fly was carried out in the laboratory and it was identified as Sarcophaga. The infestation was resolved extracting the larvae and washing the affected area with an antiseptic solution. PMID- 1589616 TI - [Sertoli-Leydig-cell ovarian tumor with a retiform pattern and heterologous elements: a rare cause of virilization]. AB - The case is presented of a young female with virilization signs and total circulating testosterone levels above 4 ng/ml, without a concomitant increase in cortisol, 17 OH-progesterone, DHEA-S, or androstenedion levels. On CT scan exam a tumoral mass in the left ovary was observed with polycystic characteristics similar to those observed in ovarian cystadenoma, inspite of the fact that most androgenic ovarian tumors are solid. The pathological study revealed an ovarian Sertoli-Leydig tumor associated to a reticular pattern with heterologous chondroid and mucinoid elements of cystadenoma. PMID- 1589617 TI - [An epidemiological study of the evolution of pneumonia in the Valencia community (1976-1980)]. AB - Pneumonia is an inflammatory process of lung parenchyma, being one of the ten first causes of death in developed countries. The data for the performance of this study have been obtained from Monografias Sanitarias: mortality statistics published by the Generalitat Valenciana for the five-year period 1976-1980. The distribution of pneumonia was analyzed according to age and sex by means of specific rates and mortality reasons. Furthermore, calculations of standardized rates and standardized mortality rates were carried out using the direct method. The results establish that in Health areas 2, 8, 9-12, 15, 16, 21 and 22 there is an increased mortality due to pneumonia. Similarly, it is note worthy the predominance of pneumonia in older groups, while no significant differences exists between sexes. PMID- 1589618 TI - [A 30-year-old women with abdominal pain, diarrhea, fever and an abdominal mass]. PMID- 1589619 TI - [Preliminary experience with BCM-IMx as a pretreatment marker of breast tumors]. PMID- 1589620 TI - [Ciprofloxacin in the ambulatory treatment of osteomyelitis in diabetic foot]. PMID- 1589621 TI - [Respiratory cryptosporidiosis in HIV patients. A report of 2 cases]. PMID- 1589622 TI - [Osteomyelitis and septic shock]. PMID- 1589623 TI - [Thoracic actinomycosis and Salmonella superinfection]. PMID- 1589624 TI - [Thrombotic thrombocytopenic purpura and breast carcinoma]. PMID- 1589625 TI - [Acute endocarditis due to Staphylococcus xylosus]. PMID- 1589626 TI - [Vincristine-induced recurrent laryngeal nerve paralysis]. PMID- 1589627 TI - [Creatinine clearance in man]. PMID- 1589628 TI - [Changes in the sensitivity of pneumococci to antibiotics. Therapeutic consequences]. AB - Streptococcus pneumoniae has a prominent role in infectious bronchopulmonary diseases. This organism is normally sensitive to a vast number of antibiotics. However, in recent years, acquired resistance against tetracyclines, macrolides, and, more recently, penicillins, has emerged. Since 1987, there is indeed a regular increase in the frequency of strains that have a lower sensitivity to penicillin G (less than 1% before 1986; 12% in 1990). However, this percentage of strains with a lower sensitivity is much more important among non-invasive as opposed to invasive organisms that are isolated from blood, pleural and spinal fluid cultures (3.3% in 1990). Among strains with abnormal sensitivity to penicillin G, there are very selective serotypes or serogroups: 4 types or groups (23, 19, 6 and 14) represent 80% of these strains. More than 80% of the strains of MIC greater than 2 mg/l are among only one stereotype, 23F. This abnormal sensitivity to penicillin G implies a modification of sensitivity to all beta lactams, but MIC increase to a variable extent depending on the antiinfectious agent. The most efficient agents against strains of lower sensitivity are amoxicillin, imipenem and parenteral third generation cephalosporins. On the other hand, for all oral first, second and third generation cephalosporins, MIC increase to levels for which seric levels that are reached hardly demonstrate convincing efficiency. Even if resistance levels are less marked as shown by strains isolated from pulmonary infections as compared to what is seen in ENT, the trend in the development of abnormal sensitivity of pneumococci to beta lactam agents urges the clinician to take into account these data in the therapeutic coverage of bronchopulmonary infections. PMID- 1589629 TI - [Severe community-acquired pneumopathy. What initial antibiotics to use?]. AB - Even if they represent only a minor percentage of all respiratory infections, acute pulmonary infections are the leading mortality cause from infectious diseases. Epidemiologic data amongst hospitalized patients with acute infections reveal mean mortality figures of 20%. The adequate assessment of severity criteria is fundamental so that patients can be oriented towards suitable hospitalized units. Risks factors to be considered are: other illnesses, age (greater than 60 years), breathing frequency greater than 30/min, diastolic blood pressure less than 60 mmHg, confusion, a PaO2 less than 60 Torr, a leukocytosis greater than 30,000 or less than 4,000/mm3, albuminemia less than 35 g/l and blood urea greater than 7 mmol/l. The association of these factors increases the risk of complications and mortality in a linear way. By contrast, the type of responsible organism is not relevant. Five microorganisms are responsible for 80 to 90% of documented acute pulmonary infections: pneumococci, Mycoplasma pneumoniae, Haemophilus influenzae, Legionella pneumophila, Myxovirus influenzae. However, direct examination of bacteriologic smear allows for a proper identification of the infectious agent in only 15% of cases. The clinician can therefore use epidemiologic, clinical and radiological findings to propose an oriented, though probable, antibiotic treatment. In these conditions, the initial treatment remains the association of an A type penicillin with an inhibitory effect on beta-lactamases and of a macrolide (or, eventually, of a fluoroquinolone) until results of bacteriologic investigations is known. No data is available to suggest the use of new third generation oral cephalosporins in the first intention treatment of acute severe pulmonary infections due to their low and inconsistent effect on pneumococcus. PMID- 1589630 TI - [Epidemiology of legionnaires' disease. From myth to reality]. AB - Legionella disease is among the leading causes of acute pulmonary infections. Nevertheless, the precise frequency remains difficult to assess because of its clinical aspects, the empirical treatment and the diagnostic requirements. According to the existing literature, the frequency of Legionella infections varies from 1 to 15% of documented pulmonary infections. In a survey carried out in 1990 in the Lyon area, the precise incidence of infections due to Legionella in daily medical practice has been estimated according to various types of practice. In general practice, only one case of Legionella infection was proved among 88 pulmonary infections. This weak incidence is also found in hospital practice: 10 cases among 398 hospitalized pulmonary infections in pneumology; none of 158 cases of severe pulmonary infections hospitalized in intensive care units. On the other hand, of 162 cases of hospitalized AIDS patients in a unit specialized in infections, two cases of Legionella infections were diagnosed. In a multidisciplinary 876 bed hospital, 16 cases of pulmonary infections due to Legionella were seen in 1990 by comparison with 32 cases in 1989 (chlorination of water since 1988). The data of Centre national de reference (Fleurette) report figures of 400 cases per year since 1985, without any change from one year to the other. These data are nevertheless underestimated. Global mortality is of 10%. No acquired resistance during the treatment is observed and infections caused by Legionella are consistently sensitive to macrolides, rifampicin and fluoroquinolones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589631 TI - [Acute pneumopathies in the aged]. AB - Acute infectious pulmonary diseases have a particular importance in elderly subjects because of their frequency and severity. This particular sensitivity to respiratory infections is linked to the global reduction in defense immune mechanisms: reduction in T-lymphocyte response in the presence of mutagens, reduction of the late hypersensitivity reactivity, alteration of B- and T lymphocytes cooperation, reduction in bacterial opsonization. The presence of associated chronic diseases like chronic obstructive airway diseases, cardiovascular diseases, diabetes, renal failure or cancers is, for a large part, responsible for these infections. The diagnosis is often difficult because of the paucity and the lack in specificity of clinical signs. Radiological and, eventually, bacteriologic investigations are most often necessary to limit the prescription of multiple antibiotic treatments that are responsible of serious side effects direct and/or related to possible drug interactions. These risks are indeed increased because of the modification in metabolism and the pharmacokinetics of antibiotics in elderly subjects. Criteria for hospitalizing elderly subjects with an acute pulmonary infection are not different from those which apply in younger patients, but they imply more awareness. It is also important to take into account socioeconomic conditions and the individual functional capacities in the initial assessment of the severity of the condition. In conclusion, the multiple aspects and the potential severity of pulmonary infections in older subjects require a particular awareness, a more precise diagnosis and the initiation of antibiotics based on a probabilistic judgment, most often during an hospitalization. PMID- 1589632 TI - [Evaluation of asthma: clinical or functional scores?]. AB - This article is a review of the clinical and functional scores used for the assessment of the severity of asthma. Dyspnea is a key feature of asthma but its severity is difficult to interpret. Subjects with continuous airway obstruction may tend to be poor sensors of their dyspnea. The addition of other symptoms such as cough, wheezing, etc. to the dyspnea score can also be criticized. An international consensus conference recently proposed a clinical and functional scale to assess the severity of asthma. A combination of clinical, drug and functional information can best express the severity of asthma. Data originating from the authors work suggest that the correlations between clinical and drug scores on the one hand and peak expiratory flow rate values on the other hand are weak. It is the authors' final impression that the severity of asthma should be judged in a global way by considering various parameters. PMID- 1589633 TI - [Oral and inhaled corticoid therapy. Rivals or partners?]. AB - Although steroids have been prescribed as antiinflammatory preparation for the treatment of asthma for many years, fear of side effects has limited their wider use. The development of new steroid derivatives administered by inhalation has reduced these risks. Oral and inhaled steroids can be used in a separate way, oral steroids being reserved for the control of acute exacerbations and inhaled steroids for the baseline treatment of chronic asthma. Inhaled and oral steroids can also be used concurrently in the same patient. Studies have shown a reduction in the dose of oral steroids in patients taking inhaled steroids. Works carried out by the Canadian research worker Toogood have addressed the question of the equivalent clinical dosing potency of inhaled and oral steroids. Finally, the reversibility of airway obstruction in subjects affected by non-specific chronic obstructive diseases might worth be assessed by using an inhaled steroid preparation. PMID- 1589634 TI - [Budesonide: efficacy and indications of low posology]. AB - Although inflammation plays a crucial role in asthma, asthma is not equivalent to inflammation. On the one hand, the relationship between the degree of airway inflammation and the level of bronchial responsiveness to pharmacological agents is not well established. On the other hand, even if late asthmatic reactions has many inflammatory characteristics, the response to the inhalation of a beta-2 adrenergic agent is generally good, which suggests some muscular contraction as well in the reduction of airway caliber. The chronic use of antiinflammatory preparations improves the level of bronchial hyperresponsiveness but this effect is not constant, does not generally result in-normal values and may be short lived after ending the administration of the drug. It is unknown as to whether the chronic use of these preparations: 1) will reduce the mortality and morbidity of asthma; 2) will be devoted of long-term side effects; 3) will be accompanied by a satisfactory compliance. A greater awareness of these potential problems should therefore be kept in mind before prescribing low-dose inhaled steroids. PMID- 1589635 TI - [Long-term tolerance of inhaled corticosteroids]. AB - The effect of inhaled steroids on adrenal glands of asthmatic subjects are often difficult to assess because subjects may have received oral steroids before. Moreover, even if the Synacthen test is abnormal, it does not necessarily mean that the adrenals are clinically inefficient. Adrenal insufficiency can certainly occur at high doses of inhaled steroids. Possible long term effects on bone are under study. Ecchymosis has been described. Oropharyngeal candidiasis is frequent but rarely symptomatic and responds well to treatment. Hoarseness is rare but troublesome. In children, inhaled steroids, even taken at low dose, can induce growth impairment. After cessation of inhaled steroids, adrenal insufficiency is only theoretical. Asthmatic flare-ups are more of a threat. Although inhaled steroids are of remarkable efficacy and tolerance, one should not exclude the possibility of long-term negative effects, especially in children. PMID- 1589636 TI - [The Turbuhaler]. AB - Metered-dose inhalers have several caveats. They contain fluorocarbons which are considered to be responsible for the depletion of the ozone layer in the stratosphere. Inhalation through metered-dose inhalers can cause cough and bronchospasm. Moreover, metered-dose inhalers are difficult to handle. Errors in using these devices have been described in 30% to 70% of subjects, the incoordination between the actuation of the device and the inhalation being the most common. The author describes the Turbuhaler made of three parts (a reservoir for the powder, the dosing chamber and the inhalation channel) and the way it works. It has been shown that the efficacy of terbutaline (in mg/mg) is equivalent with the Turbuhaler and the metered-dose inhaled. Several studies that are reviewed by the author show that the Turbuhaler is the inhalation device that is the easiest to use. PMID- 1589637 TI - [Physiopathology of asthma]. AB - The author reviews some of the physiopathologic aspects of asthma. Airway obstruction is related to several factors which include airway contraction, sub mucosal edema and mucus hypersecretion. Bronchial hyperresponsiveness is related to inflammatory factors which occur at the periphery of the airways. Inflammatory cells include mastocytes, macrophages, lymphocytes, eosinophils, neutrophils and platelets. These cells can release inflammatory mediators including metabolites of cyclooxygenase pathway, leukotrienes and PAF. Chronic inflammatory changes can occur and can be explained by the persisting release of inflammatory mediators and abnormalities of cellular activation. Cytokines might be involved in this process as shown by the author's recent findings. PMID- 1589638 TI - [Hyperventilation--central neurogenic hyperventilation]. PMID- 1589639 TI - [Hyperventilation due to peripheral origin]. PMID- 1589640 TI - [Myoclonus of the respiratory muscles: description of pathophysiology]. PMID- 1589641 TI - [Hyperventilation and breathlessness]. PMID- 1589642 TI - [Chronic hyperventilation]. PMID- 1589643 TI - [Hyperventilation; physiologic effects and treatment]. PMID- 1589644 TI - [Preliminary clinical experience in use of intravascular blood gas exchanger (IVBGE)]. PMID- 1589645 TI - [Is radiofrequency catheter ablation available for treatment of ventricular tachycardias?--Effects of sequential unipolar applications using multiple electrode catheter]. AB - The purpose of this study was to examine the effects of radiofrequency energy delivered to the canine endocardium in sequential unipolar applications using multipolar electrode catheter for treatment of ventricular tachycardias. Radiofrequency energy generated by the newly designed device (500 kHz) was delivered to the ventricular myocardium by a quadripolar electrode catheter. The device could indicate output and voltage and could calculate myocardial impedance. In order to determine the power of the ablation in vivo, sequential unipolar application was performed with various output in vitro. A continuous endocardial ablation was achieved with output beyond 15 W and with duration of 5 sec per one pole. According to our measurement, the myocardial impedance in vivo was about three times as large as that in vitro. Therefore, minimal output of 45 W in vivo was applied in the same manner in vitro, which resulted in continuous belt-shaped endocardial ablated lesion. Ventricular stimuli after sequential unipolar applications did not induce ventricular tachycardia in any of the dogs. We conclude that radiofrequency sequential unipolar application using the newly designed device produces a large ablated area and may be suitable for ablation of the foci of ventricular tachycardias. PMID- 1589646 TI - [Evaluation of myocardial oxygen extraction dynamics in syndrome X by continuous measurement of coronary sinus oxygen saturation and its relation to clinical features]. AB - We investigated the relation of myocardial oxygen extraction dynamics to pathophysiology and clinical features in syndrome X. In patients with syndrome X who underwent cardiac catheterization, coronary sinus oxygen saturation (n = 21) during rapid atrial pacing loading was continuously measured using a fiberoptic catheter system, and global and regional left ventricular function (n = 14) was evaluated before and immediately after pacing loading. Results were as follows: 1) In 5 of 21 patients with syndrome X, coronary sinus oxygen saturation during pacing loading fell less than 5% below the baseline without any impairments of global and regional left ventricular function. 2) In 16 patients with syndrome X, coronary sinus oxygen saturation during the pacing loading continuously fell over 5% below the baseline accompanied by impairment of both global and regional left ventricular function. The decrease in regional wall motion of the left ventricle was mainly observed in the apical area. These findings imply that changes in myocardial oxygen extraction dynamics in syndrome X during rapid atrial pacing may show the extent of a patchy area where myocardial oxygen demand-supply imbalance occurs due to coronary microcirculatory disturbances. PMID- 1589647 TI - [A rabbit model for evaluation of a small-caliber vascular graft]. AB - A method for experimental study for a long small-caliber vascular graft was developed and used to observe the healing process and antithrombogenicity of a high porosity fabric prostheses. Eight rabbits weighing 3 kg were used. A left thoracotomy was performed. The thoracic descending aorta was clamped with two vascular clamps and excised in the middle without temporary shunt. A 15 cm long by 4.0 mm ID segment of a fabric prostheses (porosity: 3000) was implanted end to end. After the blood flow of the aorta was restarted, the graft remained in a big loop shape in the thoracic cavity. Total operating time was less than one hour. Three animals were lost because of bleeding from the anastomotic sites (2) and bleeding from the lung (1) within 12 hrs, but paraplegia was not produced. One animal died because of an occlusion in the graft at 16 days after implantation. The remaining 4 animals survived. In two out of these four animals, an angiography was performed. Two grafts were still patent at four weeks. One of these two was explanted and its smooth surface was observed. The major advantage of this technique is that we could evaluate a long small-caliber vascular graft in a small animal. PMID- 1589648 TI - [Thallium-201 myocardial imaging in cases involving transposition of the great arteries after arterial switch operation]. AB - Forty patients, including 39 with complete transposition of the great arteries and one with double outlet right ventricle, after arterial switch operation were studied with thallium myocardial imaging (TMI). In patients who had post operative cardiac catheterization, the TMI findings were compared to those of catheterization studies. The right ventricular to left ventricular up-take ratio (RV/LV ratio) shown by TMI correlated well with the right-to-left ventricular systolic pressure ratio. Supravalvular pulmonic stenosis with significant pressure gradient was found in 14 patients, and all of them were noted to have an elevated RV/LV ratio. This ratio was noted to increase progressively on serial TMI studies in most patients who had significant pulmonic stenosis on first postoperative catheterization. Three patients had significant perfusion defects indicating the presence of myocardial damage. Two of them had occlusion of the coronary artery, but the other one had no coronary abnormalities able to be found by coronary arteriography. Air embolism or some other intra-operative transient insults to the myocardium were most likely to have been responsible for the perfusion defects. Thus, TMI was valuable as one of the noninvasive tools for follow-up of patients after arterial switching, particularly for those with late complications such as supravalvular pulmonic stenosis and coronary problems. PMID- 1589649 TI - [A case of unstable angina pectoris associated with an active phase of polymyositis]. AB - We report a case of unstable angina in an active phase of polymyositis. A 51 year old man was admitted with a diagnosis of polymyositis and unstable angina with ST elevation on prolonged rest chest pain. Rest anginal attack which had been refractory to conventional antianginal medications was controlled by high dose of glucocorticosteroid. Electrocardiography revealed multifocal premature ventricular contraction. Since silent ischemia on exercise persisted, percutaneous transluminal coronary angioplasty (PTCA) was performed on a stenotic lesion in the left anterior descending artery. Since there was recurrent anginal attack, re-PTCA was carried out at the same site. He was discharged in a good condition. This case is considered to be associated with cardiac involvement of polymyositis because of ventricular arrhythmia, persistent increased serum levels of CPK-MB, and the marked benefits of corticosteroid against unstable angina. In addition, clinical manifestations, coronary arteriographic findings, and increased plasma levels of thrombin-antithrombin III complex suggest that cardiac involvement in polymyositis accelerates intracoronary thrombus formation and/or coronary spasm. PMID- 1589650 TI - [A case of myocardial infarction in a young man with systemic lupus erythematosus]. AB - Apparently the incidence of coronary artery disease in systemic lupus erythematosus (SLE) has been increasing. However, most of the cases had been treated with corticosteroids, and had atherosclerotic lesions in the coronary arterial tree. A 21-year-old man with latent and untreated SLE had an attack of acute myocardial infarction. Coronary arteriography showed eccentric stenotic lesion at the proximal segment of the right coronary artery. One week later, in the 2nd coronary arteriography, this stenotic lesion was not able to be recognized. We supposed that the coronary artery occlusion was due to thrombus formation, and was not related to atherosclerosis, arteritis and embolus. He had no coronary risk factors. Laboratory data showed lymphocytopenia, proteinuria, positive antinuclear antibody, and positive LE cell, and the case was diagnosed as SLE. Subsequent investigations showed the presence of antibodies to cardiolipin. It was suggested that anticardiolipin antibody and other thrombogenic factors were the causes of the coronary occlusive thrombosis in this patient with SLE. PMID- 1589651 TI - [A case of brain stem encephalitis complicated with bifascicular block caused by rubella virus]. AB - We reported a case of a 29-year-old man who had been in good health until contracting brain stem encephalitis due to a rubella virus 5 years previously, at which time the ECG revealed complete right bundle branch block and right axis deviation. An ECG obtained 6 months earlier had been within normal limits. Since yearly health checkups continued to show the same abnormalities, the patient was admitted for closer examination. At the time of admission, physical findings and blood tests revealed no abnormalities. No cardiomegaly nor pulmonary congestion was observed on chest X-rays either at the time of the original illness or at this time. An endomyocardial biopsy specimen obtained from the right ventricle revealed size variation of cardiac myocytes, moderate disarrangement, and mild myocardial interstitial fibrosis, indicative of post-myocarditic changes. The above findings suggest that bifascicular block (right bundle branch and posterior fascicle) appeared at the time of the rubella virus infection, in the pathogenesis of which the involvement of myocarditis was strongly suspected. Some patients developing myocarditis do not manifest cardiac symptoms such as heart failure. In these cases, conduction disturbances are the sole sequelae. To differentiate pathogenesis in such cases, endomyocardial biopsy was thought to be of value. PMID- 1589652 TI - [A case of isolated tricuspid regurgitation associated with persistent left superior vena cava]. AB - We presented a rare case of isolated tricuspid regurgitation (TR) associated with persistent left superior vena cava (PLSVC). A 69-year old female was admitted to our hospital because of arrhythmia and cardiomegaly. Pansystolic cardiac murmur of Levine 2/6 was heard in her Erb's area. Remarkable cardiomegaly was revealed as 78% of cardiothoracic ratio and electrocardiographic findings showed atrial fibrillation. Echocardiographically, obvious dilatation of coronary sinus, right atrium and right ventricle were recognized and left atrium was also dilated moderately. Although results of right cardiac catheterization showed almost normal pressure, remarkable TR of grade IV was registered by Doppler echocardiography. Additional diagnosis of PLSVC drained to dilated coronary sinus was made by venography from the left antecubital vein. But evidence of other cardiac shunt diseases and other abnormalities which might be a cause of TR was negligible. It is reported, in general, that PLSVC drained to coronary sinus occurs asymptomatically, and there is no accepted theory that PLSVC is able to be a cause of TR alone. So, we diagnosed our case as rare isolated TR associated with PLSVC, and because only two such cases are reported in Japanese, we reported it. PMID- 1589653 TI - [A case of acute isolated (Fiedler's) myocarditis diagnosed by histopathological study with rapid unfortunate course]. AB - A 65 year-old-man was admitted to our hospital complaining of orthopnea and precordial oppressive feeling. Chest roentgenogram revealed congestive heart failure. Electrocardiogram revealed acute myocardial infarction-like pattern. Serum enzymes (CPK, GOT, LDH) were slightly elevated, but serum antiviral antibodies were not elevated. Echocardiogram showed severe symmetrical left ventricular (LV) hypertrophy, but there was no abnormality of LV wall motion. He died of progressive heart failure and ventricular fibrillation on the second hospital day. A necropsy was performed within one hour of death. The heart was enlarged (690 g) with both left and right ventricular hypertrophy. The myocardium disclosed a diffuse infiltration predominantly of eosinophilic leucocytes. Histopathological study revealed giant cell formation and granulomatous lesions in the myocardium. There was no overt endocarditis or pericarditis. We concluded that the severe LV hypertrophy was due to myocardial inflammatory swelling. From these findings, we diagnosed this case as acute isolated (Fielder's) myocarditis. PMID- 1589654 TI - Creative learning: an evaluation of the development and implementation of a self directed program in environmental medicine for health professionals concerned about hazardous substance exposure. PMID- 1589655 TI - Measuring quality of life in general practice. PMID- 1589656 TI - Smoking habits before, during and after pregnancy among Swedish women and their partners in suburban Stockholm. AB - Smoking habits of pregnant women and their partners at three health centres in Stockholm, Sweden, were monitored by a postal questionnaire. Of 582 women enlisted at the antenatal clinics, 433 (74%) were included. 253 (58%) women and 230 (53%) partners responded. 30% of the women were smokers at the start of pregnancy, compared with 27% of the men. During pregnancy 18% continued to smoke, and after the birth of the child 21% were smokers. The male partners stopped or decreased smoking less often. Fewer women aged 25 or more were smokers. The number of heavy smokers decreased considerably during and after pregnancy. The women were more prone to stop smoking if the partner was a non-smoker. 87% made some restriction in their smoking habits after the baby was born. PMID- 1589657 TI - Production of betalactamase by respiratory tract bacteria in children: relationship to antibiotic use. AB - Sales of antibiotics have increased in Sweden during the past decade. This has been paralleled by an increase in the frequency of beta-lactamase-producing respiratory tract bacteria. To investigate the effects of regional differences in use of antibiotics on beta-lactamase production in respiratory tract bacteria, we collected nasopharyngeal specimens and information about antibiotic use from 1133 children attending day-care centres in four rural municipalities with low use, and one urban municipality with high use of antibiotics, use being assessed from pharmacy sales. The frequency of beta-lactamase production among isolates of Branhamella catarrhalis and Moraxella nonliquefaciens was significantly higher in the urban municipality. This appeared to be a long-term ecological effect of differences in the level of use of antibiotics between the urban and rural populations, rather than an effect of recent antibiotic treatment of individual patients. PMID- 1589658 TI - One hundred and fifty men with urinary incontinence. I. Demography and medical history. AB - 150 community-living Norwegian men with urinary incontinence were interviewed. They were recruited to the study after responding to a marketing campaign for incontinence aids. Almost 40% of the men had suffered from urinary incontinence for more than 5 years. Anamnestically, 14 had predominantly stress incontinence, 50 had urge incontinence, 54 had mixed incontinence, and 32 were unclassified. The severity was mostly slight or moderate. About 70% had experienced a variety of other medical conditions, many of which may cause or aggravate incontinence. Likewise, 50% took regular medication. 28% had undergone prostatectomy. PMID- 1589659 TI - One hundred and fifty men with urinary incontinence. II. Help seeking and self care. AB - 150 Norwegian men with urinary incontinence living in the community were interviewed about their self care and help seeking behaviour. They were recruited to the study after responding to a marketing campaign for incontinence aids. A wide variety of control measures was used, the most popular being absorbent products. 25 men had not used any control measure. 104 men had mentioned their problem to a doctor. The consultation rate increased with the severity of urinary incontinence but was not correlated to its type or duration, nor to the patient's age or marital status. A multiple regression analysis showed that none of the recorded variables explained more than 10% of the total variation in consultation rate, and that no combination of variables explained more than 12%. Subtle personal and idiosyncratic mechanisms are probably more important, thus presenting a challenge for the case-finding strategy in general practice for urinary incontinence in men. PMID- 1589660 TI - Health for all through research on primary care. AB - This paper first explores what Health for All (HFA) means as a policy goal. It calls for major changes in health care. In the European Region of WHO, 38 targets show how approaches to health problems, lifestyles, environment, health care and support measures (e.g., planning, management and training) should be changed to reach the goal. These changes must be based on sound scientific knowledge. HFA therefore also calls for a health research policy. The second part looks at the research implications of HFA. WHO analyzed the 38 targets to see what kind of research would help to achieve them. This analysis resulted in two health research policy documents jointly called Research for health for all (RHFA). The first one explains why a country needs a health research policy. The second volume identifies the research necessary to reach the targets. The third part describes the research priorities identified in RHFA and shows their relevance for the primary health care research community. It ends with the prerequisites needed to make research for HFA possible. They include changes in the incentives for and financing of research, personnel development, research organization and communication between the researchers and decision-makers. PMID- 1589662 TI - Attitudes to primary-care gynaecology among family physicians and gynaecologists in Israel. AB - A postal questionnaire was sent to a random sample of Israeli gynaecologists and family physicians to study their attitudes to primary care gynaecology. The gynaecologists (n = 50) tended to think that family physicians should not be involved at all, except for adolescent sex education. The family physicians (n = 60) thought that they should be managing menstrual disorders, vaginal discharges, family planning counselling, prescription of oral contraceptives, insertion of intrauterine devices, routine antenatal and postnatal care, sexually transmitted diseases, breast examinations, and menopausal counselling. Both professions agreed that high risk pregnancies, hospital deliveries, infertility, and PAP smears were in the gynaecologists' domain. The younger family physicians and those in rural practice held these views more strongly than their older colleagues in urban practice. The results are discussed in the light of the patients' and the doctors' diverse interests. PMID- 1589661 TI - The use of selected interventions in monitoring primary health care implementation in rural Nigeria. AB - Nigeria's Primary Health Care (PHC)-based health system development aims to strengthen PHC in the local government areas (LGA) through technical planning and implementation that emphasize maternal and child health services. Convenient variables, including expanded programme on immunization (EPI), antenatal care (ANC) utilization and attended births, were selected as interventions to monitor the progress of implementation of PHC activities during 1985-90 in Odukpani LGA. Analysis of available data at the LGA showed that immunization coverage for most EPI antigens increased; ANC services showed increased utilization; health worker attended births increased as traditional birth deliveries declined during the period. Some of the increases were modest but are considered important. The study offers a pilot approach to monitoring implementation of PHC activities in Odukpani LGA. The implications of the findings for similar studies are discussed. PMID- 1589663 TI - Dutch general practitioners' management of patients with distal osteoarthritic symptoms. AB - Little is known about general practitioners' (GPs') policy with respect to patients with distal osteoarthritic symptoms. Therefore, the medical records of 196 patients with distal osteoarthritis were studied with respect to the GPs' management. In addition, 14 Dutch GPs' were interviewed on their management of patients with distal osteoarthritic symptoms. We found varying approaches with no consensus among GPs' and no relationship between their policies and GP, patient, or illness characteristics. We believe there is a need to develop a consensus on GPs' policy with respect to osteoarthritic patients, and to develop standards, based on research in general practice. PMID- 1589664 TI - The value of exercise tests after acute myocardial infarction. AB - The aim of the present study was to relate the clinical course in patients after a first acute myocardial infarction with the response to exercise-tests performed one month after discharge. 90 consecutive patients who suffered an acute myocardial infarction for the first time were followed-up after 12 months in general practice. Six patients had died, and nine patients had suffered another MI. 23 patients were being treated for heart failure, 51 for angina pectoris, and 8 for arrhythmias. 14 patients received treatment for both heart failure and angina pectoris. Of the patients at work, 17.6% did not return to work because of the heart disease. 80 patients were in function groups I-II and 10 in function groups III-IV (New York Heart Association's Classification). Occurrence of ST segment displacements was without prognostic value. Left ventricular function index (dRPP) and working capacity (W) were predictive with respect to mortality, heart failure, and angina pectoris requiring drug treatment. Exercise tests following acute myocardial infarction could not predict the chances of returning to work. PMID- 1589665 TI - Caregivers' experience of providing care for demented persons living at home. AB - Caregivers providing home-care for demented persons answered a questionnaire concerning what was satisfactory or problematic when providing home-care. They were also asked what needs/wishes they had for themselves and for the demented persons. The findings reflected the impact of a functioning interpersonal relationship between the caregiver and the demented person and his family. The difficulties in handling problematic behaviour, and the necessity to be able to stimulate and provide activities for the demented were also emphasized. Moreover, the caregivers stressed their role as supporters of the patients' families, their need for more and better cooperation with the staff of the psychogeriatric clinic, and their need for training and supervision in how to manage their relationship with the demented person. Hence, it seems urgent to try to practise and evaluate systematic clinical guidance to provide knowledge and systematic supervision about how to manage demented persons in their own social context so that they can stay in their homes. PMID- 1589666 TI - Maternal cigarette smoking, breast-feeding, and respiratory tract infections in infancy. A population-based cohort study. AB - This population-based study comprised 192 mothers and their infants; 58 mothers were smokers and 134 non-smokers. At the 18-month infant check-up at the child health clinic, mothers were questioned about the length of the breast-feeding period, both exclusively breast-feeding and overall breast-feeding time. The numbers of antibiotic-treated respiratory tract infections (RTIs) during the first year of life were noted during a scrutiny of records at the district physician's surgery and child health clinic of the Health Centre, and at the paediatric and ENT departments of the Central Hospital. We were unable to find any connection between the duration of breast-feeding and the number of antibiotic-treated RTIs in the infants. This applied to both exclusively breast feeding period and overall breast-feeding period. Further, it was shown that infants of smokers were affected by RTIs more often than those of non-smokers, the incidence figures being 1.16 vs. 0.76 antibiotic courses per infant and year, respectively. Moreover, infants of smokers were breast-fed for a shorter period than those of non-smokers, the mean values being 3.3 vs. 4.3 months, respectively, for the period of exclusively breast-feeding, and 5.0 vs. 7.2 months, respectively, for the overall breast-feeding period. PMID- 1589667 TI - Trends in use of health care services in Swedish primary care district. A ten year perspective. AB - In a study that covered ten years a questionnaire about use of health care facilities was mailed each autumn to 1/60 representative samples of the population in Sollentuna, a Swedish primary care district with three health centres. Primary care was the health care form with the greatest contact area with the population studied. However, the strengthening of district physician resources at one of the three health centres did not, in the long term, lead to more people coming into contact with this form of medical care. It was more common for those who visited a private doctor or school/company doctor also to consult a district physician than vice versa. Similarly, hospital patients visited the health centre to a greater degree than patients of health centres visited hospitals. The only long-term change in the flow of patients that could be registered was a reduction in the number of patients who visited hospital emergency departments. It is concluded that the implementation of an annual survey may be considerably more helpful than more sparse investigations in distinguishing between temporary fluctuations and real changes. PMID- 1589669 TI - Factors provoking lower urinary tract infection in women. AB - Our aim was to evaluate possible risk factors, other than sexual activity, for urinary tract infection (UTI) in women. A case-control study was designed. 50 cases and 50 controls were included. A larger fraction of cases than controls reported that episodes of the following preceded the UTI: voluntary deferred voiding (Odds ratio 5.0, 95% confidence interval 1.7; 20.1), cold hands (4.7, 1.3; 25.3), cold feet (5.8, 2.0; 22.8) and cold buttocks (5.5, 1.2; 51.0). Cold body parts should be further evaluated as a possible risk factor for UTI in UTI prone women. PMID- 1589668 TI - Amoxicillin in treatment of acute uncomplicated exacerbations of chronic bronchitis. A double-blind, placebo-controlled multicentre study in general practice. AB - The aim of the study was to evaluate whether a broad-spectrum penicillin, amoxicillin, was superior to placebo in resolving symptoms of acute exacerbations of chronic bronchitis in patients from general practice. 131 general practitioners included 278 patients over a period of 30 months. The patients were randomly assigned to treatment with amoxicillin 750 mg b.i.d. or corresponding placebo for 7 days. Patients with pneumonia, a temperature above 38.5 degrees C or heart rate over 100 were excluded for safety reasons. The main effect parameter--the doctors' overall evaluation of the treatment--did not demonstrate any statistically significant difference between amoxicillin or placebo, 63% versus 64% of the patients. Resolution of symptoms was obtained by 19% (25/132) of the patients in the amoxicillin group compared with 10% (13/136) of the patients in the placebo group, P = 0.03. The present findings do not favour routine use of antibiotics in an attempt to improve the course of acute exacerbations as defined in this study in patients with chronic bronchitis. PMID- 1589670 TI - Peer comparison feedback to achieve rational and economical drug therapy in general practice: a controlled intervention study. AB - The aim of the study was to describe and evaluate a controlled intervention to achieve more rational and economical drug therapy in general practice. The strategy was based on peer comparison feedback and encouragement of local peer group discussions. Seven districts comprising 53, and 6 districts comprising 55 eligible practices constituted the intervention and control groups respectively. The process was evaluated by questionnaires to the GPs. 88% found the feedback diagrams relevant, and 74% expressed a wish for information about prescribing of particular drugs. The outcome evaluation was based on computerized registration of prescriptions. During the study period of 6 months the median costs per prescription increased significantly in the control group, whereas there was no statistically significant change in the intervention group. There were no significant effects on the prescribed amounts. PMID- 1589671 TI - [The treatment of hyperlipidemias]. PMID- 1589672 TI - [Pregnancy, thyroid function and autoimmune diseases]. PMID- 1589673 TI - [Physiopathology of short bowel syndrome]. PMID- 1589674 TI - [What is your roentgen diagnosis? Deep-seated colonic ileus and pneumatosis cystoides intestinalis]. PMID- 1589675 TI - [Current treatment methods in skin tumors]. AB - Modern aspects of treatment for malignant melanoma, basalioma and cutaneous lymphomas are reviewed. Cytokines have been proposed as immunostimulants in adjuvant therapy (destruction of residual tumor) for malignant melanoma or at high doses for treatment of metastatic melanoma. Basalioma is the most common tumor of the skin, prone to recurrence because of its iceberg-like subclinical growth-pattern. Micrographic surgery is best adapted to this growth behaviour by following the extent of the tumor in all directions by special histopathologic techniques thus permitting radical excision. Primary lymphomas of the skin although rare (1 in 100,000 per year) prevail and cumulate because of the long course over years and decades. New treatment avenues have opened by topical use of phospholipids and cytostatic drugs i. e. carmustine (BCNU). PMID- 1589676 TI - [Toxic contact dermatitis]. AB - Two types of irritant contact dermatitis are described: the acute and the cumulative toxic contact dermatitis. The acute contact dermatitis causes many different lesions on the skin. The most frequent irritants are acids and alkaline solutions. Chemical burns by hydrofluoric acid are the most dangerous of all injuries caused by acids and need special treatment. Cumulative toxic dermatitis is often observed on the back of the hands and forearms after exposure of several weeks or months. Repeated skin contact by harmless products can also cause cumulative toxic dermatitis. Xerodermatitis is the most frequent type of cumulative toxic dermatitis. Phototoxic reactions of the skin are not caused by immunologic factors, and they are only observed at sun-exposed areas. Drugs can cause frequently phototoxic reactions. The lesions on the UV-A-exposed skin are mainly erythema and blisters. PMID- 1589677 TI - [Toxic and drug-induced lesions of the pulmonary parenchyma]. AB - Pulmonary tissue may be damaged by certain toxins or drugs in a dose-dependent way or by a hypersensitivity reaction. Pathological changes consist of a permeability pulmonary edema, an alveolar hemorrhage, an alveolitis and finally the formation of pulmonary fibrosis. Ingestion of the weed killer paraquat may induce a rapidly progressive and lethal form of fibrosing alveolitis, the inhalation of nitrous oxides may elicit lung edema. The most common drugs causing lung damage are cytotoxic agents, often used in combination, and the noncytotoxic drugs amiodarone and nitrofurantoin. PMID- 1589678 TI - [Retinal detachment]. AB - Retinal detachment can be successfully treated today in over 90% of patients. For a good functional prognosis early diagnosis and appropriate initial treatment remain crucial. Symptoms of incipient retinal detachment are those of acute posterior detachment of the vitreous body with "mouches volantes" and/or photopsia. At risk and thus to be examined urgently if such symptoms occur are patients with previous history of detachment, severe myopia, aphakia or pseudophakia. Prophylactic treatment of degenerative retinal lesions that can be interpreted as precursors of detachment is highly controversial and only indicated in patients with particular risk factors. Research in surgical treatment of retinal detachment focuses on improvement of functional result by improved instruments and standardized operative techniques. PMID- 1589679 TI - [Degenerative calcification of mitral and aortic valves]. AB - The heart of the elderly is characterized by increased occurrence of characteristic calcifications on mitral and aortic valves. These valves have been found calcified in persons older than 70 years at about equal frequency, in nearly 50% of these individuals simultaneously. A calcified mitral ring was more common in females of all age classes, aortic calcifications showed a less marked difference for gender. Only the most severe calcifications of the mitral ring have hemodynamic consequences. The clinical significance of these calcifications lie in their propensity for bacterial colonisation. The risk for infective endocarditis rises tenfold. Aortic valves, calcified by degenerative processes, lead to more pronounced alterations of hemodynamics. In nearly one half of the patients this type of calcification results in stenosis with corresponding left ventricular hypertrophy. Since coronary arteriosclerosis has a similar age distribution the risk for ischemic heart disease is increased. Early and particularly frequent calcifications of the aortic valve develop in patients with bicuspid valves. Risk for infective endocarditis is also raised by a factor of ten in patients with calcified aortic valve. PMID- 1589680 TI - Non-standard combination of radiation and surgery for esophageal cancer. AB - Three schemes of nonstandard combination of irradiation and surgery for esophageal cancer are presented: individual approach (IA), dynamic planning (DP), and sequential scheme (SS). In IA preoperative fractionation is adjusted to the tumor size. In DP esophageal resection is performed only in nonresponders to small-fraction 40-45 Gy radiation. In SS surgery is performed after radiation with greater than 50 Gy for residual esophageal tumor or reappearance of the tumor. PMID- 1589681 TI - One-stage surgery for esophageal cancer. AB - Of 102 patients operated on from 1985 to 1989, 75 patients had esophageal cancer, 21 had cancer of the cardia involving the thoracic portion of the esophagus, 3 had gastroesophageal cancer, 2 had leiomyosarcoma, and 1 had an epidermoid lesion of the middle third of the esophagus and cardial adenocarcinoma. All of them underwent extirpation of the esophagus with one-stage esophagoplasty and the establishment of a cervical anastomosis. The esophagus was replaced by an isoperistaltic tube made from the greater curvature of the stomach in 95 patients, from the colon in 4, and from the small intestine in 3 patients. The abdominocervical approach was employed in 86 patients and with additional right side thoracotomy in 16 patients. The gastric graft was formed using a laser scalpel and suture instruments. Postoperative mortality was 4.9% (i.e., 5 deaths). A number of surgical approaches through the abdomen are suggested, permitting visual exposure of the esophagus up to the aortic arch. PMID- 1589682 TI - Surgery of localized cardioesophageal cancer. AB - In cardioesophageal cancer the 5-year survival was 52.5% for operations on patients without regional metastasis or involvement of the serous gastric membrane. When regional metastases were present, the 5-year-survival was 23.3%. When the whole wall was invaded with the tumor but there were no metastases to the regional lymph nodes, the 5-year survival increased to 38.2%. In cases involving both invasion and metastases, the percentage of 5-year survivors was 13.3%. These findings indicate the prognostic significance of metastatic spread to regional lymph nodes. When cardioesophageal tumor invasion spreads beyond the original tumor site, combined resection yields apparently similar results. The experience of this clinic permits us to conclude that potential progress in obtaining improved long-term results for esophageal cancer management is dependent on advances in lymph node dissection methods and the search for effective combinations of systemic treatment, involving chemotherapy or immunotherapy. PMID- 1589683 TI - Successive radiation and surgical treatment of esophageal cancer. AB - On the basis of our extensive experience with radiation therapy, surgery, and combined therapy in the treatment of esophageal cancer, we substantiate a basis for giving irradiation followed by surgery. With the high efficacy of radiotherapy (RT), achieving tumor regression of more than 75% with a dose 40-50 Gy, it is expedient to continue RT using a radical programme. This may lead to full recovery without any surgical intervention. However, these patients must be followed-up. If tumor growth continues or if there appears a recurrence of tumor later, a radical operation must be performed (56 clinical cases). During the operation, extirpation of the esophagus with esophagoplasty, or its resection with a one-staged reconstruction with the gastrointestinal tract, is possible. The latter is preferred, as it not only increases the patients' life-span with comparatively low operative mortality, but results in full recovery of some patients. PMID- 1589684 TI - Surgical aspects in the treatment of esophageal cancer. AB - In operation for esophageal cancer the authors distinguish amputation and rehabilitation stages. Analysis of survival rate has shown that extended esophageal resections are preferable to typical resections. The differences are significant both in locally limited cancer and cancer with lymphogenous metastases. One-stage esophagoplasty is advisable, since after Dobromyslov Torek's operation multistage esophagoplasty could be completed only in one-third of the patients due to recurrence of the disease and their general weakness. In Lewis' and Garlock's one-stage operations it is preferable to perform an "end-to side" anastomosis with immersion of the first line of anastomotic sutures and the adjacent esophageal part into the anterior gastric wall. Postoperative mortality for Lewis' and Garlock's operations was 14.7% and 8.3%, respectively. Combined operations are justified only when one-stage esophagoplasty is performed. PMID- 1589685 TI - Surgery for elderly patients with cancer of the cardia. AB - During the past 22 years, the operability rate has been 62.2% for patients 60 years or older, with cancer of the cardia (319/475). The resectability rate has been 66.2% (211/319). Proximal resection of the stomach with resection of the lower third of the esophagus was performed on 156 patients, and gastrectomy on 65. During the last 5 years the operative mortality has decreased from 24.2 to 12.5%. The major causes of death were leakage of anastomosis, pneumonia, acute cardiovascular failures, and myocardial infarction. The 5-year survival rate was 25.2%. The rate of relapse following radical surgery was 14.4% (23 operated patients). The mean duration of life for patients undergoing radical surgery was 26.3 months and those who had had explorative or palliative interventions was 4.5 to 9.3 months. PMID- 1589686 TI - Some aspects of multiple esophageal and gastric cancer. AB - This paper deals with data on 65 patients with multiple primaries. There were synchronous and metachronous, double carcinomas of the esophagus (8), carcinomas of the esophagus and stomach (18), esophagus and lung (10), and stomach and lung (29). Problems of diagnosis and treatment results are discussed. Indications for surgery should be determined by the extent of the two primaries. Only radical surgery with extirpation of both tumors may lead to relatively favorable results. The treatment only of single carcinoma (either by surgery, or radio- and chemotherapy) is not beneficial in patients with synchronous lesions. Thorough attention should be given to the patient's complaints and adequate follow-up investigation pursued in order to detect second (and following) primaries as soon as possible. PMID- 1589687 TI - Preoperative diagnosis of esophageal cancer spread. AB - Results are presented of combined examinations of esophageal cancer patients. Current status and potentialities in preoperative diagnosis of local and metastatic cancer of the esophagus are specified for the following techniques: (1) roentgenological: roentgenoscopy and roentgenography of the esophagus, survey chest X-ray; (2) endoscopic: esophagoscopy and tracheobronchoscopy; (3) X-ray computed tomography (CT): esophageal, chest, hepatic paracardial and retroperitoneal lymph node CT; (4) radionuclide: 67Ca-citrate chest scanning and 99Tc-glucoheptonate scanning of the liver; (5) ultrasound tomography: identification of metastases to paracardial and retroperitoneal lymph nodes and to the liver. The validity of the combined use of the above techniques in preoperative diagnosis of local and metastatic cancer of the esophagus is substantiated, as well as surgical policy based on the information obtained with the above diagnostic examinations. PMID- 1589688 TI - Gastric esophagoplasty for esophageal carcinoma. AB - The 30 years experience includes 293 esophageal resections for carcinoma, completed with esophagogastrostomy at the thoracic or cervical level. Resections were performed according to the method of Garlock (73), Lewis (178), and Dobromyslov-Torek (36). This paper compares isoperistaltic esophagoplasty with whole or resected stomach (257) and antiperistaltic esophagoplasty with a tube from the greater gastric curvature (36). We will assess the choice of an esophageal substitute, the creation of esophagogastric anastomosis, and the functional consequences of surgical intervention. PMID- 1589689 TI - [Impact of the Free-Trade Treaty in clinical laboratories and Mexican medicine]. PMID- 1589690 TI - [Allergenic flora in the Valle de Mexico. Relationship with food hypersensitivity of vegetable origin (IV)]. PMID- 1589691 TI - [Prevalence of bronchial asthma in a student population in Guadalajara City, Jal. Mexico]. AB - In an intent to know the bronchial Asthma prevalence in our school children we performed a prospective descriptive survey of 1064 children. The diagnosis was confirmed by clinical history, physical examination and skin test. We found an accumulative prevalence of 12.8% with predominance in males. The 93.4% had confirmed diagnosis, the 30% had need for hospitalization in the last school year. We also analyze the age of onset, family history of allergy and school absenteeism. Bronchial asthma is a common ill at school age, affecting school attendance and family habits and finances. PMID- 1589692 TI - [Sports in the multidisciplinary treatment of the asthmatic child]. AB - A comparative analytical study was undertaken in 18 asthmatic children were incorporated in a physical rehabilitation program participating in swimming and physical exercises which lasted one year. During this time their parents also attended an informative course so that they could obtain a greater understanding of the illness and its treatment as well as their having received familial psychiatric evaluations which focussed on a better solution to the conflicts this illness presents. Significant changes were noted in the spirometrical results being those as noted FEV1 (p less than 0.0125) as apposed to FVC (NS), and FEF 25 75% (NS). The results obtained from the flexibility and resistance exercises were statistically significant in comparison to the velocity ones which were not (NS), the psychiatric evaluations show a better familiar relations less manipulated and less agressions between asthmatic children and his parents. We have come to the conclusion that participation in sports, specifically swimming, is a necessary activity for the integral treatment of the asthmatic patients. PMID- 1589693 TI - TPS in breast cancer--a comparative study with carcinoembryonic antigen and CA 15 3. AB - The serum levels of tissue polypeptide antigen were determined using the M3 monoclonal antibody (TPS) and compared with the serum levels of carcinoembryonic antigen (CEA) and breast carcinoma antigen 15-3 (CA 15-3) in 96 patients with benign breast tumors, in 25 breast cancer patients with no evidence of disease, in 139 preoperative breast cancer patients and in 298 samples of 25 breast cancer patients during therapy monitoring (4-22 samples per patient). The 95th percentile of TPS in 89 apparently healthy females was 51 U/l. The 95th percentile of TPS in patients with benign breast tumors was 55 U/l. The maximum TPS level in breast cancer patients with no evidence of disease was 56 U/l. In preoperative breast cancer the number of patients with TPS levels above the 95th percentile of TPS in benign breast tumors was significantly higher in stage III breast cancer as compared with stage I+II. This was not established for CEA and CA 15-3. During therapy monitoring TPS followed the course of the disease faster than CEA and CA 15-3 in patients with bone metastases, liver metastases, lung metastases and pleural effusion, with one exception. TPS levels could be correlated with progression of disease in patients with normal and steady levels of CEA and/or CA 15-3. PMID- 1589694 TI - Use of serum tumor markers in the differential diagnosis between ovarian and colorectal adenocarcinomas. AB - In the search for a method to facilitate the preoperative discrimination of ovarian carcinomas from colorectal carcinomas serum levels of 6 tumor markers were measured in 47 patients presenting with ovarian cancer and compared to levels found in 24 female patients with advanced, untreated colorectal cancer. The markers studied were CA 125, CA 15.3, CA 19.9, CEA and two recently developed mucin markers, CA M29 and CA M26. Levels of CA 125, CA 15.3, CEA and CA M29 showed significant differences between both groups. In predicting ovarian cancer, sensitivity was highest for CA 125 at 94% (35 U/ml cutoff level). However, the specificity of CA 125 was at 71% low. Specificity increased significantly by using a combination of a CA 125-positive score (greater than 35 U/ml) and a simultaneous negative CEA score (less than or equal to 5 ng/ml) (specificity 100%, sensitivity 81%). A CA 125/CEA serum ratio greater than 25 resulted in the highest discriminative power with a specificity of 100% and a sensitivity of 91% resulting in an overall test accuracy of 94%. It is concluded that the serum tumor markers used, especially a combination of CA 125 and CEA, are helpful in the preoperative differential diagnosis between adenocarcinomas of ovarian and colorectal origin. PMID- 1589695 TI - Abnormal expression of neurofilament proteins in Ewing's sarcoma cell cultures. AB - A neural origin of Ewing's sarcoma (ES) has often been suggested and we have demonstrated neurofilament protein expression in ES cells. However, only the 200 kD subunit has been revealed in all of the ES cells analyzed. The 160- and 68-kD subunits were always absent. For these reasons, we have attempted to induce neural differentiation in 3 ES cell lines with different types of inducers: tetradecanoylphorbol-13-acetate (TPA) retinoic acid and nerve growth factor. When the cell lines were cultured for 7 days with TPA (10(-9) M) or retinoic acid (10( 7) M), only the 68-kD neurofilament subunit was slightly induced. No inducation was obtained when nerve growth factor was used, even at a 21-day culture. These results are in agreement with the putative neural origin of ES and may indicate an abnormal expression of neurofilament proteins in this tumor. PMID- 1589696 TI - The reactivity of anti-porcine gastric inhibitory polypeptide (GIP) rabbit serum R65 with synthetic human and porcine GIP. AB - Porcine gastric inhibitory peptide (GIP) has been used extensively as a standard and as [125I]-GIP in radio-immunoassays (RIAs) to determine immunoreactive GIP (IR GIP) in human plasma even though porcine and human GIP have slightly different amino acid sequences. A rabbit anti-porcine GIP serum (R65) which has been widely used in the RIA for IR GIP reacts with a part of the GIP molecule which is identical in human and porcine GIP. In order to validate the use of R65 the IR GIP contents of synthetic human and porcine GIP were measured, using natural porcine GIP as standard, and found to be 40% and 35% on a weight basis respectively. These materials were considered unsuitable for use as RIA standards. The IR GIP in samples of human plasma was then assayed with 125I labelled synthetic human or porcine GIP using natural porcine GIP as standard. The values measured for IR GIP did not depend on the labelled peptide used (p = 0.84, n = 81) and were linearly correlated (r = 0.98, p less than 0.001, n = 81). It is concluded that the value of IR GIP measured in human plasma using R65 and standards of porcine GIP is linearly proportional to the level of human GIP in plasma. PMID- 1589697 TI - Oxygen radicals and scavenger enzymes in ischaemia-reperfusion injury of skeletal muscle. AB - In this study the protective effects of removing oxygen free radicals during ischaemia and reperfusion of skeletal muscle were investigated. The bilateral gracilis muscle model was used in six dogs. Both muscles were made ischaemic for 4 h, followed by reperfusion for 60 min. To remove oxygen free radicals, superoxide dismutase and catalase were given 10 min before ischaemia and during the first 30 min of reperfusion in one muscle; the other muscle served as a control. Muscle blood flow was recorded during the first 35 min of reperfusion. At the end of reperfusion the contents of high-energy phosphates and glycogen were measured. Furthermore, the metabolic burst of leukocytes (chemiluminescence) was determined. Flow as well as creatine phosphate were always highest in the treated muscles as compared with the control muscles (p less than 0.05). Adenosine triphosphate and glycogen were highest in all but one case. Spontaneous leukocyte chemiluminescence was significantly reduced in venous blood from the control muscle and insignificantly reduced in blood from the treated muscle as compared with blood from the aorta. The results are indirect evidence that reactive oxygen metabolites play a role in the genesis of ischaemia-reperfusion injury of skeletal muscle and that treatment with scavenger enzymes may have protective effects. PMID- 1589698 TI - Oxidative metabolic status of blood monocytes and alveolar macrophages in the spectrum of human pulmonary tuberculosis. AB - The oxidative metabolic status of blood monocytes (BM) and alveolar macrophages (AM) in patients with active pulmonary tuberculosis (TB) (n = 40) and in successfully treated patients (n = 40) was assessed and compared with that of healthy control subjects (n = 40). Oxygen free radical (OFR) generation, measured by chemiluminescence (CL) and cytochrome c reduction assay and confirmed by using scavengers of different OFR, was suppressed in AM of the pulmonary TB group compared with healthy controls, whereas it was enhanced in BM. Successfully treated patients showed partial recovery of CL and cytochrome c reduction in AM. There was no significant change in BM of patients after having been treated. The overall capacity to generate OFR was markedly suppressed upon in vitro stimulation with latex in both BM and AM of TB patients. The observed suppressed oxidative metabolic activity in BM and AM was further elucidated by studying the molecular mechanism of respiratory burst. The activities of NADPH oxidase and enzymes of the hexose monophosphate (HMP) shunt were significantly (p less than 0.05) decreased in BM and AM of pulmonary TB patients compared with healthy controls. Patients who had been treated showed marked recovery of NADPH oxidase and HMP shunt activity. The present study suggests that tubercle bacilli escape the microbicidal action of macrophages as a result of suppressed OFR generation caused by decreased activity of HMP shunt, leading to decreased levels of NADPH, thereby preventing NADPH oxidase from working at its full capacity. PMID- 1589699 TI - Effect of conditioning of beta-migrating very low-density lipoprotein with macrophages on the accumulation of cholesteryl esters in smooth muscle cells. AB - The mechanism of cholesteryl ester accumulation in smooth muscle cells was investigated. Incubation of smooth muscle cells with beta-migrating very low density lipoprotein (beta-VLDL, d less than 1.006) for 24 h did not result in accumulation of oil red O-stained particles in the cells. However, incubation of smooth muscle cells with beta-VLDL in the presence of rat peritoneal macrophages induced accumulation of oil red O-stained granules in smooth muscle cells. Medium containing [3H]-cholesteryl linoleate-labelled beta-VLDL ([3H]beta-VLDL) that was conditioned with rat peritoneal macrophages increased the incorporation of [3H] cholesterol and the cholesteryl ester content in smooth muscle cells, whereas unconditioned [3H]beta-VLDL did not. On zonal ultracentrifugation of conditioned medium containing [3H]beta-VLDL with macrophages, radioactivity was found at two peaks of density 1.150 and less than 1.006. This new fraction with d = 1.150 (peak II) migrated at beta-positions, the same as that of low-density lipoprotein (LDL) on agarose gel electrophoresis, and contained cholesteryl esters (28%), free cholesterol (15%) and phospholipid (43%). When smooth muscle cells were incubated with the peak II fraction, the radioactivity incorporated into smooth muscle cells and the cholesterol ester content of the cells increased. These results show that aortic smooth muscle cells in cooperation with macrophages can accumulate cholesteryl ester from beta-VLDL. PMID- 1589700 TI - A new protective solution for hypothermic storage of free vein grafts in cardiovascular surgery. AB - In order to reduce the operative injury of the endothelium in free reversed vein grafts, cultured human endothelial cells were used to test the optimal concentration of the constituents of a flushing solution for improved protection of the endothelium. The following solution proved to be the most suitable when tested at 20 degrees C; mannitol 160 mmol l-1, glucose 15 mmol l-1, NaCl 30 mmol l-1, KHCO3 5 mmol l-1, K2SO4 10 mmol l-1, KH2PO4 4 mmol l-1, MgSO4 20 mmol l-1, CaCl2 1.5 mmol l-1, potassium citrate 1.0 mmol l-1, Pluronic F-68 20 mg l-1, HEPES 4 mmol l-1, HEPES-Na 6 mmol l-1, pH 7.25, osmolality 325 mosmol kg-1 H2O. When endothelial cell injury was measured by a 51Cr-release assay, the new solution protected human endothelial cells in culture during hypothermic incubation better than isotonic NaCl, St Thomas' cardioplegic solution or Krebs Henseleit's buffer. Transmission and scanning electron microscopy showed that the endothelium of human saphenous vein grafts was well preserved following 6 h of incubation at 20 degrees C with the new solution. As determined by morphometry using scanning electron microscopy, the endothelium of free porcine vein grafts was better preserved after incubation for 2 h at 20 degrees C with the new solution than with either isotonic NaCl (p = 0.02) or diluted, heparinized blood (p = 0.02) as the incubation medium, all cases observed following 2 h of subsequent arterial flow. The present study indicates that the endothelium of free vein grafts can be well protected against hypothermia when the flushing and irrigation fluid has a composition favouring endothelial protection. It appears likely that such treatment of vein grafts will reduce the frequency of vein graft narrowing and occlusion, post-operatively. PMID- 1589701 TI - Lipid profile in 100 men with moderate hypertension treated for 1 year with atenolol or hydrochlorothiazide plus amiloride: a double-blind, randomized study. AB - A double-blind randomized study comparing the effects of 1 year's treatment with atenolol (A) 50 mg or hydrochlorothiazide 25 mg plus amiloride 5 mg (Moduretic (M)) on the lipid profile was performed in 100 hypertensive men (mean age 47, range 22-64 years). After 4 weeks' wash-out and 4 weeks on placebo therapy subjects were randomized to either A or M therapy and followed up every third month for 1 year. If the diastolic blood pressure (DBP) was greater than or equal to 95 mmHg at a subsequent visit, the doses were doubled (n = 17 for A and n = 12 for M) and, if DBP was still greater than or equal to 95 mmHg on double dose, nifedipine 20 mg b.d. was added (n = 15 for A and n = 27 for M, p less than 0.05). The lowering of heart rate (p = 0.0001) and DBP (p = 0.005) was more pronounced with A after 1 year. During that time no significant treatment differences were noted for total cholesterol, low-density lipoprotein (LDL) cholesterol or apoproteins A and B. High-density lipoprotein (HDL) cholesterol decreased from a mean of 1.19 (+/- 0.36) mmol l-1 to 1.13 (+/- 0.35) with A, and increased from 1.14 (+/- 0.30) mmol l-1 to 1.22 (+/- 0.28) with M, and this treatment difference was significant (p = 0.0002). The triglycerides increased from 2.0 (+/- 1.2) mmol l-1 to 2.3 (+/- 1.6) in the A group and did not change with M treatment (p = 0.02) for treatment difference). In view of similar effects on cholesterol, LDL cholesterol and apoproteins, the prognostic importance of the observed treatment differences on HDL cholesterol and triglycerides remains to be established. PMID- 1589702 TI - Interaction of liquid aluminium phosphate and aluminium hydroxide with the gastric acid profile. Influence of food components and timing of meals. AB - AlPO4 is generally perceived as a particularly weak antacid. Its neutralizing capacity, when evaluated with the classical Fordtran test at the pH 3 standard, is several times smaller than that of Al(OH)3, which is considered a particularly potent antacid. This difference of in vitro reactivity of the two antacids is largely due to the fact that the pKa value is considerably lower for AlPO4 than for Al(OH)3. The object of this study was to evaluate in vivo and in vitro the impact of the pKa value of these antacids on their efficacy at low pH values and the modulation of their neutralizing capacity through proteins. Since both preparations display a much closer antacid activity at pH 2, we felt it appropriate to reevaluate the comparative in vivo neutralizing capacity of the two antacids at doses matched with their in vitro reactivity at pH 2. In vivo antacid effects were measured by ambulant pH-metry in 18 healthy volunteers after randomized ingestion of carbohydrate or protein meals. Antacid or placebo medication was given 1 and 3 h after meals. At pH 3.0, the standard milieu of the Fordtran test, preparation A, composed of Al(OH)3 and a small fraction of Mg(OH)2, displayed in vitro a neutralizing capacity of 4.4 mmol/ml, whereas this was 0.18 mmol/ml for preparation B, composed solely of AlPO4 (p less than 0.001). When tested at pH 1, 1.5, and 2, however, the ratio between A and B was below 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589703 TI - Changes in the gastrointestinal mucosa after long-distance running. AB - Two groups of long-distance runners were investigated for the effect of marathon running on the gastrointestinal mucosa. In one group gastric erosions with bleeding were found in five of nine subjects, mostly localized to the corpus region. The relative gastric blood flow measured by endoscopic laser Doppler flowmetry was slightly decreased in the cardia region (from 7.0 to 5.8; p less than 0.05) but unchanged in the other parts of the stomach, including the erosive lesions. In another group (n = 8) all the subjects showed a substantial increase in the urinary excretion of 51Cr-labeled ethylenediaminetetraacetic acid after oral intake, which indicates an increase in the intestinal permeability. There is reason to suggest that long-distance running affects the integrity of the gastric and the intestinal mucosa. PMID- 1589704 TI - Protein kinase C activity of colonic mucosa in ulcerative colitis. AB - Protein kinase C (PKC) activity was measured in the inflamed colonic mucosa of 24 patients with ulcerative colitis and in the normal colonic mucosa of 10 patients with other benign diseases. The particulate fraction activity in ulcerative colitis mucosa was significantly increased compared with that of normal mucosa (320 +/- 47 versus 200 +/- 30 pmol/min/mg protein; p less than 0.05). Inflamed ulcerative colitis mucosa also showed significantly increased total PKC activity in the particulate fractions compared with normal mucosa (147 +/- 26 versus 37 +/ 8 pmol/min/mg tissue; p less than 0.05). Mucosal samples from ulcerative colitis patients were divided into 12 with mild and 12 with severe inflammation by histologic examination. The particulate PKC activity of severely inflamed mucosa was significantly lower than that of mildly inflamed mucosa (p less than 0.05). These results indicate that colonic inflammation in ulcerative colitis may be associated with altered cellular PKC activity. PMID- 1589706 TI - The influence of induced hyperglycaemia on the characteristics of intestinal motility and bile kinetics in healthy men. AB - Simultaneous recording of duodenal motility and biliary scintigraphy by continuous infusion of 99mTc-dimethyl-iminodiacetic acid was performed in 16 healthy fasted men, of whom eight had an intravenous glucose bolus injection immediately after the passage of a duodenal phase III of the migrating motor complex (MMC). This was followed by a continuous intravenous infusion of glucose. Characteristics of the time-activity curves from the gallbladder area and intestinal area were related to phase activity of the duodenal MMC. The median duration of the entire MMC cycle was significantly shorter in the glucose group than in the group without glucose. The difference was caused by shortening of phase II. Spontaneous gallbladder emptying appeared in all eight subjects from the group without glucose but in only a single subject from the glucose group. The relative amount of liver bile diverted to the gallbladder in the entire cycle was significantly higher in the subjects who received glucose, and in four subjects all the hepatic bile was diverted to the gallbladder. The results demonstrate that induced hyperglycaemia exerts a pronounced effect on gastrointestinal motility and bile kinetics. Available evidence suggests that the effects are caused by a 'medical vagotomy'. PMID- 1589705 TI - Helicobacter pylori eradication with doxycycline-metronidazole-bismuth subcitrate triple therapy. AB - Triple therapy containing tetracycline HCl is currently among the most efficient combination therapies for eradication of Helicobacter pylori. Substitution of doxycycline for tetracycline HCl offers advantages of less frequent dosing and extrarenal excretion. In this study patients with duodenal ulcer or non-ulcer dyspepsia positive for H. pylori were randomized to either doxycycline or tetracycline HCl triple therapy in conjunction with bismuth subcitrate and metronidazole. Of the 34 patients taking doxycycline, only 22 (65%) achieved H. pylori eradication at the 4-week rebiopsy, compared with 36 of 39 (92%) taking tetracycline HCl (p = 0.004). We conclude that doxycycline-containing triple therapy is less effective for H. pylori eradication and offers no clinical advantage over tetracycline HCl-containing triple therapy. PMID- 1589707 TI - Fecal immunoreactive lipase: a new tubeless pancreatic function test. AB - Immunoreactive lipase (IRL) was measured in 368 stool samples from 231 individuals by means of a new enzyme-linked immunoabsorbent assay technic, to test its validity as an indicator of exocrine pancreatic insufficiency. Ninety seven stool samples from 64 healthy volunteers showed a logarithmically normal distribution of IRL values and a median IRL concentration of 17 micrograms/g (range, 2.75-117.3 micrograms/g) with a statistically calculated lower normal limit of 4 micrograms/g. In 100 stool samples from patients with chronic pancreatitis and proven steatorrhea the median IRL concentration of 6 micrograms/g (range, 0.002-107 micrograms/g) was significantly lower than that of normal controls and of 52 stool samples from patients with chronic pancreatitis without steatorrhea (IRL, 40 micrograms/g; range, 0.55-302 micrograms/g), 45 stool samples from 23 patients with celiac disease (IRL, 96 micrograms/g; range, 6.05-563 micrograms/g), and 30 stool samples from 26 patients with chronic diarrhea (IRL, 57 micrograms/g; range, 4.2-573 micrograms/g). It is concluded that fecal IRL is a promising new enzyme test with low diagnostic sensitivity (34%) but excellent diagnostic specificity (98%) in chronic pancreatitis and for diagnostic study of chronic diarrheal disorders. In contrast to fecal chymotrypsin, the test results are unaffected by pancreatic enzyme replacement therapy. PMID- 1589708 TI - Viability, prostaglandin E2 production, and protein handling in normal and inflamed human colonic mucosa cultured for up to 48 h in vitro. AB - Human colonic mucosa obtained from colon cancer resections ('normal') and from colectomies owing to ulcerative colitis (inflamed) were cultured for up to 48 h in vitro. The 3H-leucine incorporation in normal tissue decreased to 52% (p less than 0.001) at 48 h compared with 24 h. The protein synthesis in normal but not in inflamed explants was significantly (p less than 0.01) improved at 48 h, reaching 72% of the 24-h value, on additions of insulin and the protease inhibitors aprotinin, soyabean trypsin inhibitor, and N alpha-tosyl-L-lysine chloromethyl ketone to the culture medium. Inflamed tissue had significant protein losses of 15% after 24 h and 29% after 48 h in culture, and the excretion of precipitable 3H-leucine-labelled proteins could be as high as 20%/24 h. A slight protein loss was observed in normal tissue after 48 h in culture, but the excretion of labelled proteins was very low (3%). The prostaglandin E2 (PGE2) production in both normal and inflamed tissue displayed an increasing non-linear pattern with time in culture, with higher values for inflamed tissue. The PGE2 release profiles and the differences in basic protein metabolism between normal and inflamed human colonic biopsy specimens in culture might reflect important characteristics of the inflammatory process. PMID- 1589709 TI - Olsalazine-related diarrhoea: does rat intestine adapt in vivo? AB - Diarrhoea may occur in up to 10% of patients with ulcerative colitis treated with olsalazine, the azolinked dimer of 5-aminosalicylic acid. However, this symptom often disappears despite continued drug medication. To examine reversibility of and adaptation to olsalazine effects on intestinal absorption, rats were fed olsalazine (4 mg/100 g body weight/day) for 0 (controls), 12, 24, and 32 days. Jejunal, ileal, and colonic loops were perfused in situ with buffer or olsalazine (11.6 mM) in a pendular perfusion system. Water and electrolyte absorption was inhibited in all intestinal segments (p less than 0.001). In the proximal small intestine, however, sodium absorption was inhibited by 61%, whereas chloride and potassium absorptions were turned into net secretion. In contrast, in ileal and colonic segments sodium, chloride, and potassium absorptions were turned into a net secretion. All inhibitory effects were reversible within a short time. Intestinal absorption remained inhibitable compared with controls (p = not significant) after chronic administration of olsalazine even for 1 month. Jejunal monosaccharide absorption was not altered by acute olsalazine perfusion. In the ileum, glucose absorption was significantly inhibited, but the inhibitory capacity of acute olsalazine application decreased significantly (p less than 0.05) depending on duration of olsalazine pretreatment (51% (controls) versus 38% (32 days)). These results point to a complex, acute, but fully reversible effect of olsalazine on intestinal passive and chloride-coupled absorptive processes. Since a mucosal adaptation to these diarrheogenic effects does not occur, the resulting increase in fluid load on the diseased colon may be important in the pathogenesis of olsalazine-related diarrhoea. PMID- 1589710 TI - Carcinoma of the pancreas and papilla of Vater: presenting symptoms, signs, and diagnosis related to stage and tumour site. A prospective multicentre trial in 472 patients. Norwegian Pancreatic Cancer Trial. AB - During the period 1984-87, 472 patients with histologically or cytologically verified carcinoma of the pancreas (n = 442) or the papilla of Vater (n = 30) were accrued. Diagnostic investigations were performed in accordance with the ordinary routines of 38 Norwegian hospitals. Jaundice at presentation, found in 47% of the patients, indicated a relatively low staging. Abdominal pain or weight loss, present in 72% and 58%, respectively, indicated higher staging. The sensitivities of the diagnostic investigations were 1) endoscopic retrograde cholangiopancreatography (ERCP), 79%, and computed tomography (CT), 75%; 2) ultrasonography (US), 57%; angiography performed in 18% to assess unresectability, sensitivity, 43%; fine-needle aspiration cytology performed in 27%, sensitivity, 86%; and percutaneous transhepatic cholangiography (PTC) performed solely on papillar and head tumours in 16%, sensitivity, 85%. In stage I, PTC and ERCP had a sensitivity of 78%; CT, 52%; and US, 40%. Patient's, physician's, and diagnostic delay averaged 1.8, 2.4, and 4.0 months, respectively. The delays were shortest in stage I and papillar carcinomas. PMID- 1589711 TI - Local deterioration of the cutaneous venoarterial reflex of the hand in cirrhosis. AB - Cutaneous focal blood perfusion and an index of cutaneous vascular resistance were determined on the dorsum and palm of the hand of 34 patients with liver cirrhosis and of 24 healthy control subjects. Tests were performed with a laser Doppler technique before and during stimulation of the vasoconstrictor venoarterial reflex, performed by means of venous occlusion of the forearm. The mean arterial blood pressure of the cirrhotics turned out to be lower than that of the controls. On the dorsum of their hands a normal blood perfusion and a reduced vascular resistance were verified, suggesting the intervention of a local autoregulatory phenomenon of the blood flow. The blood perfusion turned out to be higher, whereas the vascular resistance was lower than the norm on the palm of the hands of cirrhotic patients who had palmar erythema, showing the presence of an anomalous non-autoregulatory vasodilation. The extent of venoarterial reflex on the dorsum of the hand turned out to be identical in the patients and controls, whereas that on the palm turned out depressed. This anomaly was present also in patients without palmar erythema, although less marked than in those with erythema. The data obtained suggest the presence of a disturbance in the functioning of the arteriovenous anastomoses (numerous in the palm but very scarce in the dorsum), superimposed on the venoarterial reflex. It may depend on the existence, in hepatic cirrhosis, of an impairment of the specialized autonomic nervous mechanisms that control temperature loss. PMID- 1589713 TI - A clinical-radiological evaluation of benzimidazoles in the management of Echinococcus granulosus cysts. AB - Nine patients with complicated hydatid disease managed with surgery and mebendazole/albendazole are presented. Five patients received albendazole (1 treatment course) and 5 patients received mebendazole (3 had 2 treatment courses, 1 had a switch-over from mebendazole to albendazole). The mean durations of treatment and follow-up were respectively 7 +/- 2.5 months and 7 +/- 2.5 months (albendazole); 13 +/- 10 months and 29 +/- 31 months (mebendazole). A superior clinical and radiological response was seen in 1 patient with disseminated intra abdominal disease on switching therapy from mebendazole to albendazole. Radiological improvement occurred in 3/5 courses of albendazole and in 2/8 courses of mebendazole. Clinical improvement occurred in 3/5 courses of albendazole and 0/8 courses of mebendazole. Radiological deterioration was demonstrated in 0/5 courses of albendazole and 2/8 courses of mebendazole. Although the impression was that albendazole was superior, good responses were also seen with mebendazole. The heterogeneity of the patients, their disease, short follow-up time, lack of more sensitive noninvasive assay techniques urges caution before firm conclusions can be drawn. PMID- 1589712 TI - Bismuth absorption from 205Bi-labelled pharmaceutical bismuth compounds used in the treatment of peptic ulcer disease. AB - The absorption of bismuth from five 205Bi-labelled pharmaceutically used bismuth compounds was studied in man. From single oral doses of all compounds under investigation only less than 0.1% bismuth was absorbed and excreted with the urine. A significantly higher absorption was observed from the colloidal bismuth subcitrate (0.042% of the dose) and the basic bismuth gallate (0.038%) than from the basic bismuth salicylate, nitrate, and aluminate (0.005-0.002%). No retention of bismuth in the whole body was found from the single dose experiment. The biologic fast-term half-lives of absorbed bismuth were calculated to be 0.12 and 1.5 days. PMID- 1589714 TI - Incidence of congenital toxoplasmosis in the Republic of Slovenia. AB - Over a 12-month period, 3959 pregnant women were systematically tested with the Sabin-Feldman dye test in order to assess the incidence of congenital toxoplasmosis in Slovenia. The results suggest that this is approximately 3/1000 live births. This relatively high incidence of congenital toxoplasmosis in Slovenia may make the costing of preventive screening programmes justifiable. PMID- 1589715 TI - Infection with Mycobacterium bovis in a patient with AIDS: a late complication of BCG vaccination. AB - We present a 28-year-old HIV-infected man with a 2-year delayed complication of BCG immunization. When immunized the man was healthy, with an unknown HIV status, but 2 years later he was diagnosed with AIDS because of a Pneumocystis carinii pneumonia. He was successfully treated and discharged in a state of good health. A few months later he presented with an enlarged lymph node and Mycobacterium bovis, BCG strain, was cultured. No sign of dissemination was found. We discuss the indications for BCG vaccination in adults, especially in areas and in populations with a high prevalence of HIV. PMID- 1589716 TI - Cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate. AB - A 27-year-old man, HIV-positive for 4 years, developed ventricular fibrillation and cardiac arrest during treatment of Pneumocystis carinii pneumonia with intravenous pentamidine isethionate. The dosage was 4 mg/kg/day for 18 days. Nephrotoxicity occurred and raised serum potassium. The plasma concentration of pentamidine was 580 nmol/l. Careful monitoring of renal and cardiac functions is recommended during intravenous therapy with pentamidine isethionate. PMID- 1589717 TI - Regional differences of Chlamydia pneumoniae as causative agent of pneumonia in Sweden. AB - A retrospective serological study was performed on sera from 1982-83 and 1989 to investigate the incidence of Chlamydia pneumoniae infection in hospital treated patients with pneumonia in Orebro County. Paired sera from 231 patients were available and 3 cases (1.3%) of C. pneumoniae infection were documented by microimmunofluorescence. The results differ from those reported by others implying regional differences of C. pneumoniae as causative agent of pneumonia. The findings from Orebro County do not support any change in current antibiotic policy and we still regard penicillin as the first drug of choice in community acquired pneumonia. PMID- 1589718 TI - Spiramycin-induced thrombocytopenia in a HIV-infected patient. PMID- 1589719 TI - Meningitis due to a multiply resistant Streptococcus pneumoniae in a child in The Netherlands. PMID- 1589720 TI - Psoas abscess due to an epidural spinal cord stimulation catheter. PMID- 1589721 TI - Adenosine deaminase (ADA) activity in cerebrospinal fluid. PMID- 1589722 TI - Neutralizing antibodies against two HIV-1 strains in consecutively collected serum samples: cross neutralization and association to HIV-1 related disease. AB - 97 sera collected during a 10-year period from 10 HIV-1 infected individuals were tested for neutralizing capacity against a virus isolate FICPH-22 obtained from a Danish AIDS patient, and the laboratory strain HTLV-IIIB. Three patterns of serum neutralizing activity were demonstrated: (a) patients developing high neutralizing activity against both HIV strains; (b) patients developing high neutralizing activity against the Danish virus isolate; and (c) patients developing only low titers of neutralizing antibodies (NA) against both HIV strains. The HTLV-IIIB strain was less sensitive to serum neutralization than the FICPH-22 isolate and the appearance of NA against HTLV-IIIB was typically lacking several years behind that against FICPH-22 indicating a broadening of the NA response over time. No difference in clinical outcome was observed comparing patients reaching high titers of NA and patients with low titers. Development of AIDS among patients reaching high titers of NA was preceded by a decline in NA titers, indicating an association of high titers of NA with the healthy carrier state and of declining or low titers of NA with disease progression. The majority of the neutralizing activity was mediated by IgG, but some neutralizing activity was demonstrated in the IgG depleted serum, indicating the presence of additional neutralizing substances in serum. PMID- 1589723 TI - Synergistic antiviral effect in vitro of azidothymidine and amphotericin B methyl ester in combination on HIV infection. AB - The nucleoside analogue azidothymidine (AZT) and the methyl ester of amphotericin B (AME) were assayed for antiviral effect on HIV infection singly and in combination. Both compounds were effective in inhibiting HIV infection of MT-4 cells. At concentrations where either compound alone had no significant effect on infection, the compounds in combination were potent inhibitors of HIV as evaluated by reduction in HIV antigen production and HIV induced cytopathic effect. These results indicate that a combination therapy employing compounds with different modes of action like AZT and AME may have synergistic antiviral properties. Amphotericin B itself significantly reduced HIV infectivity in vitro and should not be used as an antifungal agent in cultures intended to propagate HIV. PMID- 1589724 TI - Prevalence of genital Chlamydia trachomatis infection among women in a Swedish primary health care area. AB - The objective of this study was to estimate the prevalence of genital chlamydial infection in an unselected population of young women by offering a screening investigation to all women between the ages of 15 and 34 in a primary health care area. Specimens were taken from both the urethra and the cervix in all participating women, and data regarding the participants' symptoms, sexual habits, contraceptive use and socioeconomic factors were also collected. The specimens were analyzed with a primary enzyme immunoassay (Syva MikroTrak) and a confirmatory direct immunofluorescence test (Syva MikroTrak). A total of 543 women were invited to the study and 374 women (68.9%) participated. 10/374 women (2.7%) were chlamydia positive and only 2 of these 10 chlamydia infected women were less than 25 years of age. The chlamydia infected women had positive tests either from the urethra (4 women) or from the cervix (6 women), and in no case the tests were positive from both locations. No statistically significant differences between the chlamydia positive and negative women were found concerning any clinical or anamnestic factor. PMID- 1589725 TI - ELISA test for antimeningococcal IgG and IgM antibodies: application to epidemiology and diagnosis. AB - We have developed an enzyme-linked immunosorbent assay (ELISA) in order to quantitate antimeningococcal IgM and IgG serum antibodies. The B:15 meningococcal strain was used as coating antigen, and class specific antibodies were detected by using alkaline phosphatase labelled rabbit anti-human IgM or IgG as conjugate. The specific IgG activity was higher in sera from healthy meningococcal carriers than non-carriers, but the difference was not statistically significant. Antimeningococcal IgM serum antibodies were more frequent in carriers that in non carriers. Acute sera from 34 patients with fulminant meningococcal disease contained less specific IgG and had a higher prevalence of IgM than healthy carriers and non-carriers. By combining measurement of antimeningococcal IgG and IgM antibodies in both acute and convalescent sera 15/18 meningococcal patients demonstrated an increase in either IgG and IgM antibodies during the hospital stay, giving a sensitivity of 83%. 8/118 individuals without meningococcal disease had detectable specific IgM antibodies in their serum, giving a clinical specificity of the test of 93%. We conclude that quantitation of specific IgG antimeningococcal antibodies by a whole bacteria ELISA test may be a useful test for the study of immunity against meningococcal disease in single individuals as well as in epidemiological studies. The combined use of the IgG and IgM tests is helpful in the diagnosis of meningococcal disease when blood or cerebrospinal fluid cultures are negative. PMID- 1589726 TI - Intestinal symptoms and serological response in patients with complicated and uncomplicated Yersinia enterocolitica infections. AB - Clinical course, serological response and effect of antibiotic treatment were evaluated in 34 patients with uncomplicated enterocolitis and in 27 patients with reactive arthritis (ReA) due to Yersinia enterocolitica. Patients participating in this prospective multicentre trial were randomised to treatment or no treatment with antibiotics. Only 3 (11%) of the patients who later developed ReA asked for medical care because of intestinal symptoms and fever and they all developed arthritis within 2 days after admission to hospital, i.e. before an etiological diagnosis was obtained. Patients with ReA had a history of milder intestinal symptoms than patients with uncomplicated enterocolitis. The peak IgA titer to Y. enterocolitica, as measured by enzyme linked immunosorbent assay, was higher in ReA patients and it was not affected by the presence of HLA-B27 antigen. On the other hand, untreated patients with uncomplicated enterocolitis had the longest duration of IgG antibodies. The duration of IgG antibody response was shortened in uncomplicated enterocolitis patients treated with antibiotics, but not in ReA patients. Treatment did not influence intestinal or ReA symptoms. It is concluded, that patients with uncomplicated enterocolitis due to Y. enterocolitica differ in intestinal symptoms and serological response, compared with patients who develop ReA. These parameters could however not be used to predict the development of arthritis in individual patients. PMID- 1589727 TI - Nosocomial pneumonia in an intensive care unit in a Danish university hospital: incidence, mortality and etiology. AB - We studied the patients admitted to the ICU at a Danish university hospital during 1 year with respect to nosocomial pneumonia (NP). Among 242 patients, who stayed more than 48 h, 23 (10%) developed NP. Patients with NP had significantly higher mortality (43% vs. 19%, p less than 0.05), longer median stay (276 h vs. 99 h, p less than 0.05) and a longer median intubation period (256 h vs. 74 h, p less than 0.05). In the NP group surgical patients were overrepresented as compared to medical patients (74% vs. 45%, p less than 0.05). Thoracotomy, treatment with H-2 blockers and immunosuppression represented significant risk factors. Considering the etiology, Enterobacteriaceae and Pseudomonas aeruginosa constituted 43% of the cases in strong contrast to the low frequency of these pathogens in community-acquired pneumonia. NP in the ICU patient is a resource consuming disease associated with a high mortality (43%), which is related to the frequent severe underlying diseases of these patients. PMID- 1589728 TI - Recurrent pneumonia: a review of 90 adult patients. AB - Recurrent pneumonia is still an important problem. In this retrospective study we reviewed the records of 90 patients with a history of 3 or more episodes of acute pneumonia. The 90 patients accounted for altogether 347 episodes of acute pneumonia, treated at the Department of Infectious Diseases, Lund. 12 patients died while being treated for pneumonia at the department. Pneumonia alone caused the death in 7 of these 12 patients. In all, 51 of the patients died during the 11-year study period. Death certificates, stating the cause of death, were available in 38 cases, and pneumonia was the direct cause of death in 15 patients. Most of the infections were community-acquired, only 47 were nosocomial, 20/90 patients suffered from disorders associated with immune deficiency, and 70 patients had other predisposing illnesses. We found a larger number of underlying immunoglobulin deficiencies (11 patients of 38 investigated) than previously reported. Of 13 patients without other known, predisposing conditions, hypogammaglobulinemia was found in 3 patients. We suggest that patients with recurrent pneumonia should be thoroughly investigated, in order to find previously unrecognized immune deficiency. PMID- 1589729 TI - Blood group non-secretors have an increased inflammatory response to urinary tract infection. AB - The aim of this study was to assess the possible relationship between secretor state and the inflammatory response to urinary tract infection (UTI). Girls with recurrent UTI were prospectively studied. They included 61 secretor and 23 non secretor individuals with 604 episodes of recurrent UTI. The response to each UTI episode was measured as the levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature as well as renal concentrating capacity and pyuria. The levels of C-reactive protein, erythrocyte sedimentation rate and the body temperature were significantly higher in non-secretors than in secretors (p less than 0.04). As a consequence, non-secretors had an increased probability of being assigned a diagnosis of acute pyelonephritis rather than asymptomatic bacteriuria (p less than 0.05). The higher inflammatory response in non-secretors was independent of the Gal alpha 1-4Gal beta adhesin expression of the infecting Escherichia coli strains. The increased inflammatory response to UTI in non-secretors might explain the accumulation of these individuals among patients with renal scarring. PMID- 1589730 TI - Effects of hip arthroplasty and peroperative dicloxacillin prophylaxis on renal function. AB - In a prospective pilot study 70 patients (age greater than 65 years) who underwent hip arthroplasty were treated with dicloxacillin, a total of 6 g given pre-, per- and postoperatively as antibiotic prophylaxis. Creatinine in serum and beta 2-microglobulin in serum and urine were determined as estimates of renal function. Values were obtained preoperatively and on days 2, 4 and 10 after operation. A slight but significant increase of serum creatinine was seen on day 2 with a gradual decrease almost down to the preoperative baseline value on day 10. Serum beta 2-microglobulin increased more gradually; the increase was significant on day 10. Raised levels of beta 2-microglobulin in urine were most pronounced: a 20-fold increase on day 2, then a slow decrease, still significant increase on day 10. This may indicate a reversible damage of proximal tubules with blocked tubular reabsorption of beta 2-microglobulin. The slightly increased levels of serum creatinine and beta 2-microglobulin would also indicate a minor reversible decrease in glomerular filtration rate. Whether these effects are caused by the operation trauma per se or by the dicloxacillin prophylaxis cannot be determined from this pilot study. It seems quite clear that hip arthroplasty with short term prophylaxis with dicloxacillin does not result in clinically important changes in renal function. PMID- 1589731 TI - Ceftazidime as initial therapy in febrile patients with acute leukemia during induction chemotherapy. Leukemia Group of Middle Sweden. AB - We studied the efficacy of ceftazidime as initial monotherapy in 82 adult patients with acute leukemia who developed 123 febrile episodes during induction chemotherapy. 88% of the patients survived their febrile episode(s), whereas 10% died of infection. When assessed at 72 h after initiation of treatment (early evaluation), 43/123 episodes (35%) had been successfully treated with ceftazidime. These 43 favourable responses were seen in 15/47 (32%) microbiologically documented infections, 20/46 (43%) clinically defined infections, and 8/30 (27%) fever of unknown origin (FUO). At the resolution of fever (late evaluation) 115 episodes were evaluable, and 48% had responded successfully to ceftazidime. Successful treatment was most frequently observed in FUO, 18/29 (62%). In contrast, only 19/44 (43%) microbiologically documented infections and 18/42 (43%) clinically defined infections were cured during ceftazidime treatment. In bacteremia the response rate was only 8/26 (31%). Thus, this study shows that although ceftazidime can be safely used for initial empirical monotherapy in neutropenic leukemia patients, the need for therapy modification is high and few patients with serious infections are cured with ceftazidime alone. PMID- 1589733 TI - [Pathogenesis of alcoholic liver disease]. AB - Excessive consumption of ethanol results in reversible redox changes in the liver that are mainly responsible for the accumulation of triglycerides and the fatty liver of the alcoholic patient. In spite of continuing alcohol abuse, only a fraction of all alcoholics will develop alcoholic hepatitis and eventually cirrhosis. Genetic predisposition and environmental factors (in particular the often poor nutrition of the alcoholic) probably play an important role in the evolution of these complications. The generation of reactive oxygen species increases during the metabolism of ethanol, but their pathogenetic role in alcoholic liver disease in man is not clear. Acetaldehyde, a metabolite of ethanol, can react with proteins and form stable adducts. Such neoantigens may elicit an immunologic response which could in part be responsible for the liver cell damage associated with excessive alcohol consumption. Since no satisfactory animal model for alcoholic liver disease exists, the relative importance of the various factors involved in alcoholic liver disease is difficult to assess. PMID- 1589732 TI - Incidence of primary toxoplasma infections during pregnancy in southern Finland: a prospective cohort study. AB - Congenital toxoplasmosis may develop after maternal primary infection during pregnancy. Since toxoplasmosis in adults is usually asymptomatic, the only way to find the pregnancies at risk of acute toxoplasmosis (i.e. seronegative mothers) is to perform serological screening of all pregnant women. We studied toxoplasma specific antibodies in 16,733 pregnant women in the first, second, and third trimesters over an 18-month period in the Helsinki area, with a population of 820,700. The participation rate in our study was 90.2% of all pregnancies in the area. The overall prevalence of toxoplasma seropositivity was 20.3%. The incidence of primary infection was 2.4/1000 pregnancies at risk. Our data on incidence suggest an annual occurrence of 131 cases of primary toxoplasma infections during pregnancy in Finland. Primary toxoplasma infection appears to be a significant risk to the fetus even in countries where the prevalence of toxoplasma seropositivity is low. The feasibility of mass screening for toxoplasma infections during pregnancy should be considered in order to reduce the morbidity and mortality due to congenital toxoplasmosis. PMID- 1589734 TI - [What does the alcoholic patient need from his family physician?]. AB - Chronic alcoholics are all too often not recognized in general practice. Diagnosis is only possible if the doctor assumes potential alcoholism in all his patients. Because of the tendency of the patient and often his family to deny alcohol dependence, diagnosis is only possible by taking psychiatric, somatic and psychosocial aspects into consideration in addition to an independent history. Questionnaires may be helpful. The severity of the dependence on alcohol is not a predictor of success in therapy. In practice, three types of alcoholics may be distinguished: (1) patients with stable social relationships; (2) patients with stable social relationships and severe anxiety or depression with alcohol abuse as an inadequate self medication; (3) patients who are not able to maintain stable relationships. The latter are unlikely to be successfully treated by a family physician. A careful classification of patients according to these simple criteria may reduce the rate of treatment failures. Therapy by the family physician is initiated with an extensive somatic, psychiatric and psychosocial work-up, and maintained by counseling and care. An important factor is close collaboration between physician and social worker. Disulfiram may be a powerful adjunct to the therapy of the family physician if supervised by a trustee. In our departments we work with alcoholics in a joint consultation service involving an internist and a psychiatrist. Two thirds of the patients who consent to supervised disulfiram remain in the program for a year. 3 months after initiation of the treatment, gamma-glutamyltransferase, ASAT, ALAT and MCV are normalized. A follow-up 5 years after treatment indicated the efficacy of this treatment. PMID- 1589736 TI - [Liver transplantation in alcoholic cirrhosis: arguments in favor]. AB - Liver transplantation for alcoholic cirrhosis is still controversial, although excellent results have been reported with careful selection of the patients. Less than 10% of candidates for liver transplantation have alcoholic cirrhosis. PMID- 1589735 TI - [Is liver transplantation for alcoholic cirrhosis justified?]. AB - The experience of a number of pioneering centers has shown that liver transplantation affords good results in alcoholic cirrhosis in terms of patient survival and social reinsertion. However, this option should be weighed thoroughly in view of its very high cost to society and the increasing difficulty of obtaining a sufficient number of organs. The first requirement is that the patient cease alcohol consumption at least 6 months prior to transplantation, since alcohol resumption seems unlikely after such a period of time; also, this delay may result in regression of liver disease, making transplantation unnecessary. Finally, approval by an ethical committee seems advisable. PMID- 1589737 TI - [Adjuvant therapy in colorectal carcinoma]. AB - Patients with colorectal carcinoma and histological evidence of regional lymph node involvement (N+ or Dukes' C) or tumor invasion into the adjacent pericolic or perirectal fat tissue (T3-T4 or Dukes' B2-B3) still have an unfavourable prognosis if treated by surgery only. In colonic cancer, several clinical studies carried out in the early 1980s using postoperative chemotherapy showed no therapeutic benefit. Only the combination of 5-fluorouracil and levamisole, used in two large randomized studies, resulted in a significant prolongation of the disease-free interval and overall survival in patients with Dukes' C colonic cancer. This treatment has few side effects. In patients with rectal cancer, it was the combination of chemo- and radiotherapy which led to therapeutic improvement: the incidence of local relapses--often very painful and distressing for the patient--was significantly reduced and overall survival prolonged. However, this combined treatment modality carries the risk of delayed toxicity with complications mainly involving the small bowel. It is the general practitioners' duty to decide, together with the specialists involved, whether an individual patient with colonic or rectal cancer appears suitable for such adjuvant treatment. PMID- 1589738 TI - [Heterosexual transmission of hepatitis-C virus]. AB - Parenteral transmission of hepatitis C virus (HCV) through blood transfusions and intravenous drug misuse is well established. Since 50% of patients with hepatitis C have no history of parenteral exposure, other ways of transmission must exist. The purpose of this study was to examine the epidemiological importance of heterosexual intercourse for transmission of HCV infection. 29 heterosexual contacts (13 men, 16 women, mean age 47 years) of 29 index patients (16 men, 13 women, mean age 49 years) with histologically und serologically documented chronic hepatitis C were questioned about parenteral exposure and sexual behaviour. Their serum samples were examined for ALT activity and anti-HCV antibodies (first-generation Ortho-HCV-ELISA). Five contacts were using condoms to prevent infection. Five of 24 contacts (21%) practising unprotected sexual intercourse, but none of 5 contacts using condoms, showed evidence of heterosexual HCV transmission: 4 were anti-HCV positive (one with elevated ALT activity) and another showed elevated ALT activity with a negative anti-HCV test. None of these contacts had a history of parenteral exposure. Our results indicate that heterosexual transmission of HCV is epidemiologically important. The true rate of infection may be even higher, for two reasons: (1) not every HCV infection is detected by the anti-HCV test, and (2) the anti-HCV test may turn negative again in uncomplicated infection. PMID- 1589739 TI - [Needlestick injuries in hospital personnel and the risk of hepatitis-B infection]. AB - The risk of employees of the University Hospital of Basel acquiring virus hepatitis B following needle stick injuries (NSI) was evaluated prospectively. Over four years, 555 NSI were reported, resulting in a mean incidence of 48 NSI/1000 persons working/year. Of the injured, 455 (82%) had previously been vaccinated against hepatitis B, 32 (6%) were HBsAg and/or anti-HBc positive, and only 65 (12%) were at risk for HBV infection. The origin of 365 (66%) of the needles implicated in the NSI was identified, and of these 15 (4%) had been contaminated with HBsAg-positive blood. None of the 555 persons with NSI developed hepatitis. We conclude that the risk of HBV infection following NSI is low at our institution, but general measures need to be enforced to reduce the incidence of NSI in view of the potential risk that other infectious diseases may be transmitted by NSI. PMID- 1589740 TI - [Liver transplantation for primary biliary cirrhosis]. AB - Primary biliary cirrhosis (PBC) is regarded as one of the optimal indications for orthotopic liver transplantation (OLT) in adults. Between July 1987 and August 1991, 7 patients had PBC as the indication for OLT. 6 were transplanted and one patient is still on the waiting list. The patients' mean age was 47 years (range: 39 to 59) and the time from diagnosis to indication for OLT was 4, 7, 8, 10, 12, 15 and 17 years. Variceal hemorrhage episodes treated by sclerotherapy (plus porta-caval shunt in one patient) occurred in 3 patients before OLT. All suffered from jaundice (mean bilirubin 232 mumol/l, range 116 to 536), weakness, anorexia and pruritus. There were no deaths in this series during a mean follow-up time of 26 months (range 6 to 43). With the exception of osteopenia, all complications of chronic liver disease were reversed by OLT. Despite numerous postoperative problems (e.g. reoperations, intense rejection episodes, cytomegalovirus infections and lumbar column fractures), the quality of life is excellent for these 6 patients. Mean bilirubin at time of last follow-up was 18 mumol/l (range 8 to 26). No evidence of PBC recurrence was found. Based on international experience confirmed by this series, we support the notion that no patient suffering from advanced PBC should be denied OLT whenever possible. PMID- 1589741 TI - [Aminopyrine breath test in hepatic auto-transplantation in pigs]. AB - The aminopyrine breath test (ABT) was performed during hepatic autotransplantation in the pig. The test is reproducible in this animal and only hepatic cytochromes perform the demethylation of aminopyrine. Ischemia, varying from 90 to 200 minutes, generated a major decrease in the elimination of the 14CO2 and a marked change in the elimination curve. In this specific model it was not possible to assess survival of the animal by the ABT. PMID- 1589742 TI - [Value of simultaneous determination of cyclosporin blood levels using specific and nonspecific methods in liver transplantation]. AB - Cyclosporine's narrow therapeutic window and the large inter- and intra individual variation of its pharmacokinetics require therapeutic monitoring. Cyclosporine is metabolized in the liver and excreted with its metabolite into the bile. An accumulation of metabolites occurs in liver dysfunction, leading to a high cyclosporine blood concentration when measured by a non-specific method (polyclonal antibodies). Specific methods (HPCL, monoclonal antibody) are therefore recommended by some authors. We evaluated the potential usefulness of simultaneous cyclosporine determination by a non-specific (fluorescent polarisation TDx, polyclonal antibodies) and a specific method (I125-RIA, monoclonal antibody). 10 patients were followed from 51 days to 32 months after hepatic transplantation. 2 patients who showed no graft rejection presented a polyclonal antibodies/monoclonal antibody ratio below or equal to 4 throughout their evolution. Other patients presented a rise of this ratio during periods of liver dysfunction, particularly in acute graft rejection. When bilirubin concentrations are plotted versus this ratio, an hysteresis is present during periods of acute rejection, but not during an episode of histological hepatitis. The same holds true for alkaline phosphatase and gamma-GT. These data suggest that this ratio could be a sensitive test for early detection of rejection. Simultaneous cyclosporine blood determination with specific and nonspecific methods may be useful in the follow-up of liver-transplanted patients. PMID- 1589743 TI - [The value of Doppler ultrasonography in gastroenterology: limitations and possibilities in the assessment of portal venous hypertension and in tumor diagnosis]. AB - Due to technical progress, duplex sonography is growing in diagnostic value in gastrointestinal imaging. Color and pulsed spectral Doppler are the methods of choice in making information on morphologic and physiologic aspects of blood flow available. Amongst the various gastroenterologic applications, two important features are presented and discussed: investigation of the mesenterico-spleno portal axis in patients with portal venous hypertension, and contributions to evaluation of primary and secondary liver tumors. PMID- 1589744 TI - [The surgical treatment of autonomous nodular goiter. Prospective long-term study]. AB - In a prospective study 287 patients with a nodular goiter and preclinical or overt hyperthyroidism (TRH-TSH unresponsiveness) underwent selective excision of the nodular goitrous tissue to prevent continuing growth and goiter recurrence and reduce concomitantly the autonomously functioning follicular tissue. Depending on the topographic location of the nodes, hilar dissection (hemithyroidectomy or extrathyroidal excision) was carried out in 44% of the patients instead of classic subtotal resection. The operative mortality was nil and the rate of recurrent nerve palsy was 2.1% of cases and 1.3% of nerves at risk respectively; in no instance did bilateral palsy or permanent hypoparathyroidism occur. Thyroid function was investigated one or more times during a period lasting from 3 months to 18 years postoperatively. One patient (0.6%) developed recurrent hyperthyroidism, and in 5 subjects euthyroid TRH-TSH unresponsiveness persisted during an observation period lasting 8-13 years postoperatively. Preclinical or overt hypothyroidism occurred depending upon the extension of goiter resection, i.e. upon the extension of nodular goitrous transformation: hypothyroidism occurred in none of the patients with unifocal (uninodular) autonomy. In 58% of patients with less than or equal to 10 g of residual thyroid tissue, and in 19% of patients with a greater than 10 g thyroid remnant, substitution with thyroxine was necessary. In 2 (2.4%) of the patients followed up for 5-18 (x = 10 +/- 3) years a goiter recurrence (euthyroid) necessitating resection developed 9 and 12 years respectively after resection of a toxic uninodular goiter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589745 TI - [Toxic necrosis following a bite by Naja nigricollis, a therapeutic challenge]. AB - The surgical approach to snake bite lesions remains controversial. As a rule surgery is not recommended. However, the attitude towards severe local effects of envenoming should be revised and treatment made more aggressive, as our case report illustrates: following envenoming by Naja nigricollis, progressive necrosis jeopardized not only the function but also the survival of the hand. In view of this observation, we believe that a restrictive attitude is debatable. At first, immediately after the bite, splinting of the upper extremity is necessary, the hand being in intrinsic-plus position. Close clinical observation is necessary to detect early necrosis or a compartmental pressure-rise. As soon as pressure rises or local necrosis is suspected, extensive debridement with fasciotomy is recommended, especially in the presence of a venom with well known local toxic effects. Soft tissue coverage necessitates extensive flap surgery, such as the pedicled radialis flap, which appears not only to guarantee skin coverage but, by its excellent blood supply, prevents necrosis and allows for regeneration of underlying tissue. Our case confirms the local cytotoxicity of the venom of Naja nigricollis. Local and general effects of the snake bite must be clearly defined. The local development deserves immediate surgical attention, while the systemic effects need intensive medical care. PMID- 1589746 TI - [Cor triatriatum in adulthood: Doppler echocardiographic diagnosis. Case report of an asymptomatic adult]. AB - Cor triatriatum is a rare cardiac malformation occurring in about 0.1% of all congenital heart disease. As symptoms are usually present soon after birth, diagnosis in adulthood is extremely rare. We describe a case of a 33-year-old asymptomatic woman who was referred for echocardiographic examination because of a postural variable systolic click. The anatomy of the malformation and the hemodynamics of the left atrium were accurately assessed by means of conventional transthoracic Doppler echocardiography. The antero-inferior course of the intraatrial membrane inserting proximal to the left atrial appendage was documented in multiple perpendicular planes of examination. All pulmonary veins drained correctly into the proximal compartment of the left atrium. Additionally, a small atrial septal defect communicated between the distal compartment of the left atrium and the right atrium. Using pulsed wave Doppler, no site of pressure gradient could be detected between the two compartments of the left atrium. Thus, conventional transthoracic Doppler echocardiography represents an adequate tool for assessing cor triatriatum in adults. The patient refused transesophageal echocardiography. PMID- 1589747 TI - Air pollution and mortality. PMID- 1589748 TI - Yeast chromosome III reveals a wealth of unknown genes. PMID- 1589749 TI - Ozone hole. Not over the Arctic-for now. PMID- 1589750 TI - Science budget. Press urges doubling for research. PMID- 1589751 TI - 'Verdicts' are in on the Gallo probe. PMID- 1589752 TI - Scientist-consultants accuse OSI of missing the pattern. PMID- 1589753 TI - FBI drops OSI leak probe. PMID- 1589754 TI - Biotech's second generation. PMID- 1589755 TI - Massachusetts woos biotech investment. PMID- 1589756 TI - Animal models point the way to human clinical trials. PMID- 1589757 TI - Alzheimer's disease: a cell biological perspective. AB - An almost bewildering number of findings concerning Alzheimer's disease mask the significant recent progress in understanding the molecular basis of some inherited forms of this disease and the proteolytic processing of proteins related to the disease. Alzheimer's disease is an amyloidosis, a condition in which certain proteins or protein fragments precipitate in various tissues as amyloid, fibrillar aggregates with a beta-pleated sheet conformation. Alzheimer's is also characterized by neuritic lesions and cell death. Some rare forms of the disease are now known to arise from a mutation in an amyloidogenic protein. Another recent insight is the discovery of an endosomal-lysosomal processing pathway capable of generating protein fragments that can deposit extracellularly as amyloid fibrils. Key future directions for cellular-based research in Alzheimer's disease include the study of membrane trafficking and the passage of intracellular material to the extracellular milieu, molecular signaling among intracellular compartments, the interaction between organelles and the neuronal cytoskeleton, and the nature of cytoskeletal reorganization after neuronal injury. PMID- 1589758 TI - Triplet repeat mutations in human disease. AB - Triplet repeats are the sites of mutation in three human heritable disorders, spinal and bulbar muscular atrophy (SBMA), fragile X syndrome, and myotonic dystrophy (DM). These repeats are GC-rich and highly polymorphic in the normal population. Fragile X syndrome and DM are examples of diseases in which premutation alleles cause little or no disease in the individual, but give rise to significantly amplified repeats in affected progeny. This newly identified mechanism of mutation has, so far, been identified in two of the most common heritable disorders, fragile X syndrome and DM, and one rare disease, SBMA. PMID- 1589759 TI - Malignant hyperthermia. AB - In humans genetically predisposed to malignant hyperthermia, anesthesia can induce skeletal muscle rigidity, hypermetabolism, and high fever, which, if not immediately reversed, can lead to tissue damage or death. The corresponding condition in swine leads to stress-induced deaths and devalued meat products. Abnormalities in the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum (the ryanodine receptor) have been implicated in the cause of both the porcine and human syndromes by physiological and biochemical studies and genetic linkage analysis. In swine, a single founder mutation in the ryanodine receptor gene (RYR1) can account for all cases of malignant hyperthermia in all breeds, but a series of different RYR1 mutations are likely to be uncovered in human families with MH. Moreover, lack of linkage between malignant hyperthermia and RYR1 in some families indicates a heterogeneous genetic basis for the human syndrome. PMID- 1589760 TI - Gaucher disease: new molecular approaches to diagnosis and treatment. AB - Gaucher disease is characterized by the accumulation of glucocerebroside, leading to enlargement of the liver and spleen and lesions in the bones. It is caused by an inherited deficiency of the enzyme glucocerebrosidase. Many mutations exist, but four of these account for over 97% of the mutations in Ashkenazi Jews, the population group in which Gaucher disease is the most common. Although there is a strong relation between the mutations and disease manifestations, genetic counseling is made difficult by the fact that within each genotype there is considerable variability in the severity of the disease. Intravenous infusion of glucocerebrosidase is an effective treatment, but the availability of enzyme replacement therapy is limited by its high cost. Marrow transplantation is also effective in treating the disease, but is rarely performed because of the risks involved. In the future gene transfer may become the treatment of choice. PMID- 1589761 TI - On the molecular genetics of retinitis pigmentosa. AB - The human retina carries specialized neurons, the rod and cone photoreceptors, which absorb and transduce light energy and transmit impulses through the optic nerve to the brain. The most prevalent group of inherited retinopathies, affecting approximately 1.5 million people, is collectively termed retinitis pigmentosa (RP). Mutations responsible for RP have now been found in two genes encoding transmembrane proteins of the rod photoreceptor outer segment disc, and a number of additional causative genes have been localized. It is likely that characterization of the majority of such genes over the next few years will lead to a substantial elucidation of the molecular pathology of this debilitating group of hereditary conditions. PMID- 1589762 TI - Human gene therapy. AB - Human gene therapy is a procedure that is being used in an attempt to treat genetic and other diseases. Eleven clinical protocols are under way at the present time, each with scientific and clinical objectives. Human genetic engineering raises unique safety, social, and ethical concerns. PMID- 1589763 TI - The role of crystal polarity in alpha-amino acid crystals for induced nucleation of ice. AB - The hydrophobic faces of single crystals of a series of pairs of racemic and chiral-resolved hydrophobic alpha-amino acids were used as a substrate, onto which water vapor has been cooled to freezing. The morphologies and molecular packing arrangements within each crystal pair are similar but only one of each pair exhibits a polar axis, parallel to the hydrophobic face exposed to water. Those crystals that have a polar axis induce a freezing point higher by 4 degrees to 5 degrees C than the corresponding crystals that do not have a polar axis. The results are interpreted in terms of an electric field mechanism that helps align the water molecules into ice-like clusters en route to crystallization. PMID- 1589764 TI - Oncogenic forms of p53 inhibit p53-regulated gene expression. AB - Mutant forms of the gene encoding the tumor suppressor p53 are found in numerous human malignancies, but the physiologic function of p53 and the effects of mutations on this function are unknown. The p53 protein binds DNA in a sequence specific manner and thus may regulate gene transcription. Cotransfection experiments showed that wild-type p53 activated the expression of genes adjacent to a p53 DNA binding site. The level of activation correlated with DNA binding in vitro. Oncogenic forms of p53 lost this activity. Moreover, all mutants inhibited the activity of coexpressed wild-type p53, providing a basis for the selection of such mutants during tumorigenesis. PMID- 1589765 TI - Cholecystokinin antianalgesia: safety cues abolish morphine analgesia. AB - Environmental stimuli that signal the occurrence of aversive or dangerous events activate endogenous opiate analgesia systems. Signals for safety (the nonoccurrence of aversive events) produce the opposite and inhibit environmentally produced analgesia. Stimuli that signal safety are now shown to abolish the analgesic effect of morphine, even when morphine is applied directly to spinal cord. Further, this antiopiate effect occurs because the environmental stimulus leads to release of the neuropeptide cholecystokinin in the spinal cord. This process may contribute to the regulation of pain and the development of opiate tolerance. PMID- 1589767 TI - Lateralization of phonetic and pitch discrimination in speech processing. AB - Cerebral activation was measured with positron emission tomography in ten human volunteers. The primary auditory cortex showed increased activity in response to noise bursts, whereas acoustically matched speech syllables activated secondary auditory cortices bilaterally. Instructions to make judgments about different attributes of the same speech signal resulted in activation of specific lateralized neural systems. Discrimination of phonetic structure led to increased activity in part of Broca's area of the left hemisphere, suggesting a role for articulatory recoding in phonetic perception. Processing changes in pitch produced activation of the right prefrontal cortex, consistent with the importance of right-hemisphere mechanisms in pitch perception. PMID- 1589766 TI - Changes in the sensory processing of olfactory signals induced by birth in sheep. AB - After giving birth, sheep and many other species form a selective bond with their offspring based on the sense of smell. Processing of olfactory signals is altered to allow the animals to perform this selective recognition. Lamb odors have little effect on either neurotransmitter release or electrical activity of neurons in the olfactory bulb before birth. However, after birth there is an increase in the number of mitral cells, the principal cells of the olfactory bulb, that respond to lamb odors, which is associated with increased cholinergic and noradrenergic neurotransmitter release. Selective recognition of lambs is accompanied by increased activity of a subset of mitral cells and release of glutamate and gamma-aminobutyric acid (GABA) from the dendrodendritic synapses between the mitral and granule cells. The relation between the release of each transmitter after birth also suggests an increased efficacy of glutamate-evoked GABA release. PMID- 1589768 TI - Neocortex development and the cell cycle. PMID- 1589769 TI - Interaction cloning: identification of a helix-loop-helix zipper protein that interacts with c-Fos. AB - A facile method for isolating genes that encode interacting proteins has been developed with a polypeptide probe that contains an amino-terminal extension with recognition sites for a monoclonal antibody, a specific endopeptidase, and a site specific protein kinase. This probe, containing the basic region-leucine zipper dimerization motif of c-Fos, was used to screen a complementary DNA library. A complementary DNA that encoded a member of the basic-helix-loop-helix-zipper (bHLH-Zip) family of proteins was isolated. The complementary DNA-encoded polypeptide FIP (Fos interacting protein) bound to oligonucleotide probes that contained DNA binding motifs for other HLH proteins. When cotransfected with c Fos, FIP stimulated transcription of an AP-1-responsive promoter. PMID- 1589770 TI - Fast perceptual learning in visual hyperacuity. AB - In many different spatial discrimination tasks, such as in determining the sign of the offset in a vernier stimulus, the human visual system exhibits hyperacuity by evaluating spatial relations with the precision of a fraction of a photoreceptor's diameter. It is proposed that this impressive performance depends in part on a fast learning process that uses relatively few examples and that occurs at an early processing stage in the visual pathway. This hypothesis is given support by the demonstration that it is possible to synthesize, from a small number of examples of a given task, a simple network that attains the required performance level. Psychophysical experiments agree with some of the key predictions of the model. In particular, fast stimulus-specific learning is found to take place in the human visual system, and this learning does not transfer between two slightly different hyperacuity tasks. PMID- 1589771 TI - Synaptotagmin: a calcium sensor on the synaptic vesicle surface. AB - Neurons release neurotransmitters by calcium-dependent exocytosis of synaptic vesicles. However, the molecular steps transducing the calcium signal into membrane fusion are still an enigma. It is reported here that synaptotagmin, a highly conserved synaptic vesicle protein, binds calcium at physiological concentrations in a complex with negatively charged phospholipids. This binding is specific for calcium and involves the cytoplasmic domain of synaptotagmin. Calcium binding is dependent on the intact oligomeric structure of synaptotagmin (it is abolished by proteolytic cleavage at a single site). These results suggest that synaptotagmin acts as a cooperative calcium receptor in exocytosis. PMID- 1589772 TI - High-frequency network oscillation in the hippocampus. AB - Pyramidal cells in the CA1 hippocampal region displayed transient network oscillations (200 hertz) during behavioral immobility, consummatory behaviors, and slow-wave sleep. Simultaneous, multisite recordings revealed temporal and spatial coherence of neuronal activity during population oscillations. Participating pyramidal cells discharged at a rate lower than the frequency of the population oscillation, and their action potentials were phase locked to the negative phase of the simultaneously recorded oscillatory field potentials. In contrast, interneurons discharged at population frequency during the field oscillations. Thus, synchronous output of cooperating CA1 pyramidal cells may serve to induce synaptic enhancement in target structures of the hippocampus. PMID- 1589773 TI - Diplomacy and the AIDS blood test. PMID- 1589774 TI - The genome project: life after Watson. PMID- 1589775 TI - A standing ovation from the troops. PMID- 1589776 TI - Britain plans large-scale sequencing center. PMID- 1589777 TI - Peer review catches congressional flak. PMID- 1589778 TI - Looking glass chemistry. PMID- 1589779 TI - HIV comes in five family groups. PMID- 1589780 TI - Neurobiology. Giving personal magnetism a whole new meaning. PMID- 1589781 TI - Dendritic spines: convergence of theory and experiment. PMID- 1589783 TI - Psychological matters. PMID- 1589782 TI - Site-specific modification of pre-mRNA: the 2'-hydroxyl groups at the splice sites. AB - A simple and efficient method for synthesizing long, site-specifically modified RNA molecules was developed whereby segments of RNA were joined with the use of bacteriophage T4 DNA ligase. A single hydrogen or O-methyl group was substituted for the 2'-hydroxyl group at either splice site of a nuclear pre-messenger RNA substrate. Splicing of the modified pre-messenger RNA's in vitro revealed that, although a 2'-hydroxyl is not absolutely required at either splice site, the 2' hydroxyl at the 3' splice site is important for the second step of splicing. These results are compared to previous studies of analogous 2'-hydroxyl groups in the self-splicing Tetrahymena group I intron. PMID- 1589784 TI - Tuberculosis rebounding. PMID- 1589785 TI - The advancement of science. PMID- 1589786 TI - Mammography trial comes under fire. PMID- 1589788 TI - Biotechnology. Is the United States losing its lead? PMID- 1589787 TI - Wellcome Trust: Britain's big biomedical spender. PMID- 1589789 TI - Researchers fret over neglect of 600 million patients. PMID- 1589790 TI - Court rules for NIH. PMID- 1589791 TI - Open season on depression. PMID- 1589792 TI - Greenhouse science survives skeptics. PMID- 1589793 TI - Does global change threaten the world food supply? PMID- 1589794 TI - Japan bids for global leadership in clean industry. PMID- 1589795 TI - The continuing case of the Florida dentist. PMID- 1589796 TI - Molecular epidemiology of HIV transmission in a dental practice. AB - Human immunodeficiency virus type 1 (HIV-1) transmission from infected patients to health-care workers has been well documented, but transmission from an infected health-care worker to a patient has not been reported. After identification of an acquired immunodeficiency syndrome (AIDS) patient who had no known risk factors for HIV infection but who had undergone an invasive procedure performed by a dentist with AIDS, six other patients of this dentist were found to be HIV-infected. Molecular biologic studies were conducted to complement the epidemiologic investigation. Portions of the HIV proviral envelope gene from each of the seven patients, the dentist, and 35 HIV-infected persons from the local geographic area were amplified by polymerase chain reaction and sequenced. Three separate comparative genetic analyses--genetic distance measurements, phylogenetic tree analysis, and amino acid signature pattern analysis--showed that the viruses from the dentist and five dental patients were closely related. These data, together with the epidemiologic investigation, indicated that these patients became infected with HIV while receiving care from a dentist with AIDS. PMID- 1589797 TI - Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity. AB - The rational design and biological actions of a new class of DNA-cleaving molecules with potent and selective anticancer activity are reported. These relatively simple enediyne-type compounds were designed from basic chemical principles to mimic the actions of the rather complex naturally occurring enediyne anticancer antibiotics, particularly dynemicin A. Equipped with locking and triggering devices, these compounds damage DNA in vitro and in vivo on activation by chemical or biological means. Their damaging effects are manifested in potent anticancer activity with remarkable selectivities. Their mechanism of action involves intracellular unlocking and triggering of a Bergman reaction, leading to highly reactive benzenoid diradicals that cause severe DNA damage. The results of these studies demonstrate the potential of these de novo designed molecules as biotechnology tools and anticancer agents. PMID- 1589798 TI - Crossover reactions between synthetic replicators yield active and inactive recombinants. AB - Self-replicating molecules can be synthesized through the covalent linkage of two complementary subunits to give a self-complementary structure. Complementarity refers to sizes, shapes, and the weak intermolecular forces involved in molecular recognition between the two subunits. In order to provide a model system for evolution at the molecular level, "crossover" or recombination experiments were staged with synthetic replicators. These reactions gave rise to new structural types. The ability (or inability) of the new recombinants to catalyze their own formation is shown to be a consequence of their molecular shapes. PMID- 1589799 TI - Reproducible imaging and dissection of plasmid DNA under liquid with the atomic force microscope. AB - Reproducible images of uncoated DNA in the atomic force microscope (AFM) have been obtained by imaging plasmid DNA on mica in n-propanol. Specially sharpened AFM tips give images with reproducible features several nanometers in size along the DNA. Plasmids can be dissected in propanol by increasing the force applied by the AFM tip at selected locations. PMID- 1589801 TI - Radionuclide therapy of intractable bone pain. PMID- 1589800 TI - Less mortality but more relapses in experimental allergic encephalomyelitis in CD8-/- mice. AB - Mice lacking in CD8 were generated from homologous recombination in embryonal stem cells at the CD8 locus and bred with the experimental allergic encephalomyelitis (EAE)-susceptible PL/JH-2u through four backcross generations to investigate the role of CD8+ T cells in this model of multiple sclerosis. The disease onset and susceptibility were similar to those of wild-type mice. However, the mutant mice had a milder acute EAE, reflected by fewer deaths, but more chronic EAE, reflected by a higher frequency of relapse. This suggests that CD8+ T lymphocytes may participate as both effectors and regulators in this animal model. PMID- 1589802 TI - Phosphorus-32 radiopharmaceuticals for the treatment of painful osseous metastases. AB - Phosphorus-32, employed as the orthophosphate or polyphosphate, can reduce or relieve the pain of osteoblastic metastases without serious hematologic toxicity, especially if used as a single injection. Uptake of this beta-emitter by osteoblastic-reactive bone and possibly by tumor and other cells can lead to pain reduction and often to cell killing. Efficacy has been demonstrated for the treatment of pain in 84% of 322 breast cancer patients and 77% of 444 prostate cancer patients found in a review of the literature. These results match those of the newer radiopharmaceuticals currently under investigation. PMID- 1589803 TI - Radionuclide therapy of intractable bone pain: emphasis on strontium-89. AB - Management of bone pain in patients with multiple osseous metastases is a significant clinical problem. Phosphorus-32 has been used as systemic radioisotope therapy for the management of bone pain for over 40 years. However, significant hematological depression usually results and its use is limited. More recently, the bone-seeking radiopharmaceuticals strontium-89, samarium-153 ethylenediaminetetramethylene phosphonic acid, and rhenium-186-hydroxyethylidene diphosphonate have all been used as palliative treatment for patients with clinically significant bone pain. Excellent clinical responses with acceptable hematological toxicity have been observed. The clinical results rival those of external beam radiation therapy, with fewer systemic and hematological side effects. Systemic radionuclide therapy is indicated in the management of patients with painful metastatic prostate cancer in bone as soon as they escape primary hormonal management. This therapy also should play a role in the management of many patients with advanced breast cancer metastatic to bone. The role of radionuclidic therapy in osseous metastases from other malignancies is still being investigated. These compounds also hold promise as primary therapy for tumors of osseous origin. Systemic radionuclide therapy of painful bony metastases will become common in nuclear medicine practice in the next decade. PMID- 1589804 TI - The management of intractable bone pain: a clinician's perspective. AB - Bone metastases occur in up to 85% of patients (at autopsy) who have breast, lung, and prostate cancer, and are a common cause of pain and neurological morbidity in patients with these and other cancers. The management of pain, the most common complication of bone metastasis, requires a knowledge of specific clinical syndromes and the associated neurological and orthopedic morbidities, as well as an understanding of current antitumor and pharmacological therapies. Knowledge of these potential complications are important in the design of clinical trials that seek to evaluate the effectiveness of new treatments for bone metastasis. Although radiation therapy in combination with analgesic drug therapies remains the mainstay of treatment, much recent interest in drugs with specific effects on bone elements, especially the osteoclast, offer the promise of providing effective pain relief with fewer side effects than is currently possible with conventional therapies. PMID- 1589805 TI - [153Sm]EDTMP: a potential therapy for bone cancer pain. AB - Reactor-produced samarium-153 (153Sm) is both a beta and gamma emitter with a physical half-life of 46.3 hours. When complexed with EDTMP, more than 50% of the administered dose localizes in bone. A therapeutic trial on patients with painful bone metastases performed at the University of Missouri produced relief in 65.4% of the patients who were evaluable. Myelotoxicity was mild and transient. For [153Sm]EDTMP to attain clinical utility, studies demonstrating its efficacy as an analgesic must be performed to exclude a "ligand analgesic effect". PMID- 1589806 TI - The biodistribution of metaiodobenzylguanidine. PMID- 1589807 TI - Biliary excretion of glucoheptonate. PMID- 1589808 TI - Asymmetrical cerebellar uptake in brain single photon emission computed tomography. PMID- 1589809 TI - Increased long-bone periosteal/cortical uptake in skeletal scintigraphy. PMID- 1589810 TI - Photopenic appearance of the hepatic lesion(s) on technetium-99m red blood cell imaging. PMID- 1589811 TI - Nuclear medicine in problems of fertility and impotence. AB - Nuclear medicine techniques may be used to test fallopian tube patency and penile vascular inflow and outflow. Radionuclide hysterosalpingography (HSP) is a readily performed method of evaluating fallopian tube patency, and is believed to be more physiologic and functionally informative than the accepted radiologic method of contrast HSP. The test is simple to perform and interpret and offers an accurate alternative to the contrast examination. For scintigraphic evaluation of impotence, blood pool studies are most useful in assessing the integrity of arterial inflow, but may also be used to generate indices of venous leak. Washout of xenon after subcutaneous injection, in the flaccid state, has been used as a measure of baseline penile perfusion, as has intracavernosal injections in the flaccid penis. Intracavernosal xenon washout during erection seems the most useful method of testing venous integrity. Washout using technetium-99m (99mTc) labeled red blood cells (99mTc-RBC) may emerge as a convenient alternative to the more technically difficult xenon examinations. PMID- 1589812 TI - State-of-the-art review: captopril renography--pathophysiological considerations and clinical observations. AB - Advances in renal angiography and revascularization techniques have renewed interest in developing a better noninvasive screening test for identifying patients with potentially correctable renovascular hypertension. Captopril renography is a promising diagnostic tool in the evaluation of the hypertensive patient. This review highlights the important pathophysiological changes in renal hemodynamics and humoral response attributable to significant renal artery stenosis, and underscores the dramatic effects of angiotensin-converting enzyme inhibition on the renovascular bed. The review also summarizes the available clinical information in captopril renography, and presents consensus recommendations on appropriate patient selection, radionuclide(s) of choice, and suggested diagnostic criteria. PMID- 1589813 TI - The sexuality of gay men with HIV infection. AB - Gay men who have been diagnosed with human immunodeficiency virus (HIV) infection are living longer, healthier lives. As a result, many experience continued sexual interest. This article, based on the author's four years as a support group facilitator for men with acquired immune deficiency syndrome (AIDS), explores the sexual needs and expression of gay men with HIV infection. Several potential positive functions of a sustained sex life for these men and the factors that inhibit sexual expression are explored. Issues influencing social work practice related to the sexual needs of this growing population are discussed; suggestions for effective and humane services are presented. PMID- 1589814 TI - Epidemiology of depression for clinicians. AB - This article reviews the epidemiology of depression and the ways this information can be useful for clinicians. The article defines frequently used epidemiological terms, presents prevalence rates and risk factors; discusses the impact and consequences of depression; and suggests arenas for prevention, early intervention, and treatment that can help clinicians in their everyday work. PMID- 1589815 TI - The substance-abusing chronically mentally ill client: prevalence, assessment, treatment, and policy concerns. PMID- 1589816 TI - AIDS needs broader, more varied coverage. PMID- 1589817 TI - [Data networking in a newly established radiology institute as exemplified by the Donau Hospital in Vienna]. PMID- 1589819 TI - [Imaging of retroperitoneal and mediastinal metastases of an adult testicular teratoma using MRT]. PMID- 1589818 TI - [The significance of arteriosclerosis in CT studies of the thorax and abdomen. Frequency and correlation with risk factors and with cardiovascular diseases]. PMID- 1589820 TI - [Duodenal diverticula: differential diagnostic considerations in CT of the abdomen]. PMID- 1589821 TI - [An expanding aneurysm of a lusoria artery]. PMID- 1589822 TI - Fortieth Anniversary--Department of Social Work Services, Long Island Jewish Medical Center, New York. PMID- 1589823 TI - Profiles on women: a global perspective. PMID- 1589824 TI - Through the looking glass: a 40 year retrospective. PMID- 1589825 TI - Young children of alcoholics: a group treatment model. AB - This paper describes a therapeutically oriented psychoeducational group treatment model designed to assist young children of alcoholics. Researchers have identified children of alcoholics as a population at risk of emotional, interpersonal and substance abuse problems. Examples are used to illustrate activities and group processes characteristic of the beginning, middle and termination phases of treatment. While this approach appears promising and can be replicated in many health care settings, controlled studies are needed to measure the model's effectiveness more precisely. PMID- 1589826 TI - "Till death do us part": the application of object relations theory to facilitate mourning in a young widows' group. AB - A group of recently widowed young women sought help at a hospital's psychiatric clinic. All had been in treatment elsewhere and felt they were "pressured to get on with living." This paper presents an object relations model of a bereavement group which ran for one year. The focus was on supporting patients' defenses and avoided any implications of extended grief as pathological. Of particular interest was the use of personal video tapes and photographs in the bereavement process. PMID- 1589827 TI - Hunger: a hospital survey. AB - Patients at a New York City municipal hospital were surveyed in 1985 and 1989 to ascertain the extent of hunger and its possible correlates. Twenty-two percent (22%) of the 382 subjects in 1985 and 23% of the 332 subjects in 1989 experienced hunger. Hunger was related significantly to homelessness, social isolation and the physical inability to buy and/or prepare food. Between 1985 and 1989, there was a large increase in the use of institutional resources for food; a decline in reliance on Food Stamps; and an increase in household density. Inpatients were found to be poorer than outpatients, and to rely more heavily upon soup kitchens. Practice, policy and research implications are noted. PMID- 1589828 TI - Helping patients in the supportive milieu of a community residence program for the chronically mentally ill: conceptual model and initial evaluation. AB - The Community Residence Program described is sponsored by an urban teaching hospital and supported by state funds. The program uses scatter-site apartments in the community to house 120 patients in a therapeutic milieu as part of their comprehensive aftercare treatment. The program stresses teaching the skills of daily living to patients with chronic, psychiatric illnesses. The conceptual model used is based on challenges and tasks appropriate for this population. Preliminary evaluation findings suggest that the program is successful in teaching patients social skills, helping them adhere to medical regimens, perform household chores and observe fire safety regulations. PMID- 1589829 TI - Laser-tissue interactions. Photochemical, photothermal, and photomechanical. AB - An overview of laser-tissue interactions is presented in terms of the physical mechanisms of interaction, the time course of tissue response, and the level of biologic structure affected. The factors that affect dosimetry of photodynamic therapy are presented. Laser dosimetry for photothermal and photomechanical interactions is outlined. PMID- 1589830 TI - Lasers in general surgery. PMID- 1589831 TI - Vascular malformations of the gastrointestinal tract. AB - The advent of fiberoptic endoscopy, which became widespread in the evaluation of gastrointestinal bleeding throughout the late 1970s and 1980s, has dramatically changed both our understanding of the extent to which vascular malformations account for gastrointestinal blood loss and our ability to treat these lesions at the time of diagnosis. Colonic vascular malformations appear to be the single most common cause of acute or recurrent gastrointestinal bleeding episodes in patients over 60 years of age, being responsible for the bleeding in as many as 35% of such patients. Although less common as a cause of upper gastrointestinal bleeding, these lesions still account for 2% to 5% of bleeding lesions in older patients. Diagnosis is accomplished by endoscopy, and the vascular malformations can then be coagulated via the endoscope using one of a number of thermal systems. The argon laser, the heater probe, and the BICAP system are all effective and safe throughout the gastrointestinal tract, especially in the cecum and right colon, where the majority of sporadic vascular malformations occur. Monopolar cautery and the Nd:YAG laser are equally efficacious, but their greater and less predictable depth of coagulation make them much less safe in the cecum and right colon. There are no apparent advantages in terms of efficacy and safety between laser treatment and the other thermal modalities. The laser has the advantage of being quicker, which is especially important when treating large or multiple lesions. The other modalities have the advantages of portability and low relative cost. Endoscopic therapy with lasers or other thermal devices is nonspecific. The effects are achieved by thermally coagulating the mucosal vascular lesions, allowing the coagulated tissue to slough, and leaving a mucosal ulceration that subsequently heals with re-epithelialization. Endoscopic coagulation has thus been reported effective in the treatment of gastrointestinal mucosal vascular lesions regardless of their etiology or characteristics. It has been effective for sporadic vascular malformations, hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease), radiation proctocolitis, the blue rubber-bleb nevus syndrome, and diffuse gastric antral vascular ectasia (the watermelon stomach). As we move through the 1990s and beyond, these endoscopic modalities offer an effective, relatively safe, and clearly less invasive treatment option for the many patients who experience acute, recurrent, or chronic gastrointestinal bleeding from any of these lesions. PMID- 1589832 TI - Laser therapy for early upper gastrointestinal carcinoma. AB - An invasive procedure generally is the first choice of therapy for the treatment of gastric cancer. The development of improved microimaging and innovative engineering, however, has established a new field of endoscopic laser therapy. This article discusses the use of high-power and low-power lasers in the treatment of early gastric cancer. PMID- 1589833 TI - Laser treatment of esophageal and gastric lesions. AB - Lasers have contributed in a significant way to the evolution of therapeutic endoscopy. Their ability to coagulate and ablate tissue precisely has been applied to a wide variety of lesions in the upper gastrointestinal tract. Meanwhile, the number of nonlaser devices has also continued to expand, making it necessary to frequently reassess their respective roles. Available evidence suggests that current laser equipment is best suited for the palliative ablation of tumors, especially in the esophagus. On the other hand, the hemostatic properties of the laser are still indicated in the control of vascular malformations but have been largely displaced in the management of peptic ulcer disease by other, more convenient and less expensive methods. With a new generation of laser equipment likely to be introduced soon, these comparisons will undoubtedly need to continue for some time. PMID- 1589834 TI - Laser therapy of colorectal carcinoma. AB - A plethora of literature is available demonstrating the efficacy of Nd:YAG laser therapy for obstructing or bleeding colorectal cancers. The in-hospital mortality and morbidity rates can be reduced when Nd:YAG laser therapy is used to avoid operative diversion prior to resection and anastomosis. The Nd:YAG laser used to control bleeding or obstruction in those patients with either widely metastatic or unresectable locoregional disease has been successful in the majority of patients and has been associated with minimal morbidity and mortality rates. This laser may be the only treatment modality that may substitute for operative diversion in hopeless clinical situations such as hemorrhage or obstruction in patients with advanced disease. The utility of photodynamic therapy for colorectal cancer will require definition in further controlled trials. PMID- 1589835 TI - Photodynamic therapy. AB - Photodynamic therapy is an experimental method for treating malignant tumors. Injection of a tumor-localizing and photosensitizing agent and its subsequent activation by an appropriate wavelength of light can lead to tumor destruction, apparently through disruption of the vascular integrity of the neoplasm. The mechanism by which the blood vessels are destroyed appears to involve damage to the endothelium and release of vasoactive substances including thromboxane. The clinical utility has yet to be completely established, but the modality seems likely to play a role in the management of a variety of neoplasms. The diagnostic potential of this technology also appears to hold considerable promise. Advances in technological support for the clinical use of photodynamic therapy seem to hold the key to its wide clinical application. PMID- 1589836 TI - Liver resection and laser hyperthermia. AB - Table 2 provides a comparison of these interstitial and in situ techniques, assessing several criteria and utilizing and expanding on an excellent review by Masters et al. The rapid advance of technology and cross-fertilization between groups using different interstitial techniques will lead to a clear understanding of the benefits and limits of each. However, there is essentially no information at the present time to suggest that these techniques should be used in lieu of hepatic resection in an attempt to cure patients who are good operative risks. There are insufficient data of a controlled nature to determine that there has been a survival or palliative benefit in many of the patients so treated. Nevertheless, as it is clear that these treatments cause tissue destruction in an appropriate nonmorbid way and that they are well tolerated with low risk to the patients, it is entirely conceivable that interstitial techniques will replace hepatic resection in some instances in the future, particularly for lesions smaller than 3 cm. PMID- 1589837 TI - Hemorrhoidectomy with lasers and other contemporary modalities. AB - Hemorrhoids should be classified so that the treatment can be individualized. Minor or asymptomatic hemorrhoids usually do not require any treatment. Diet modification is a useful adjunct in all degrees of hemorrhoids. Fixation procedures may be employed in the office for first-, second-, and minor third degree hemorrhoids. These techniques are valuable in elderly and poor-risk patients. Excisions may be performed by standard instruments or lasers with good results. These techniques may be employed with local anesthesia and in an outpatient setting. Lasers may be effective as either a fixation device or an excisional tool. The problem is cost and maintenance of the equipment and the cost of the disposable apparatus. If the equipment is already available or can be shared for multidisciplinary use, hemorrhoidectomy can be accomplished in a cost effective manner with excellent results. PMID- 1589838 TI - Vascular applications of lasers. AB - There have been major advances in laser technology and in our understanding of the effects of laser energy on blood vessels. This, in turn, has led to the many clinical applications of lasers in patients with vascular disease. The clinical results of laser endarterectomy, laser angioplasty, laser-assisted balloon angioplasty, laser-assisted vascular anastomoses, and the future of lasers in cardiovascular disease are discussed. PMID- 1589839 TI - New technologies and future applications of surgical lasers. The right tool for the right job. AB - The real future of surgical lasers, and indeed of surgery itself, will depend on the integration of the surgeon into a system incorporating real-time tissue sensors, computer-directed robotic manipulation, and laser-tissue interactions that are customized to the clinical task. The human surgeon will operate as the central judgmental element in this mechanized and semiautomated laser surgical system. Only then will we really be able to make use of the subtle and varied laser-tissue effects now being discovered. PMID- 1589840 TI - Doctor Tulp, I presume? PMID- 1589841 TI - Anatomic basis of tracheobronchial reconstruction by intercostal flap. AB - A feasibility study was carried out to standardise the use of the intercostal muscle flap (ICF) for reconstruction of the posterior wall of the trachea and bronchi. The program consisted of two stages. Morphologically, in anatomic specimens, intercostal muscle flaps were dissected that could be used whatever the morphotype of the subject. Ten human cadavers were dissected after a right thoracotomy in the 6th right intercostal space, providing flaps 12 to 18 cm long and 1.5 to 3 cm wide. Experimentally, studies were made on 7 dogs of the functional and anatomopathologic aspects of the reconstruction at the 20th postoperative day. The results showed impermeability and rapid healing at endoscopy on the 10th postoperative day in every case as well as regeneration of ciliated epithelium in 6 of the 7 cases. The ICF may therefore be considered for losses of tracheobronchial substance, whether accidental, spontaneous (fistulae) or deliberate (surgery for malignant or benign lesions). PMID- 1589842 TI - The venous vascularization of the corpus callosum in man. AB - The vascularization of the corpus callosum in Man is studied in 20 brains. Their vascular system is injected with Indian ink and gelatin. The corpus callosum is drained by callosal veins and callosocingulate veins towards the deep venous system of the brain. Most of these veins run downwards and join together at the central level of the corpus callosum. They then form the subependymal veins, which form the septal veins and the medial atrial vein. All these vessels are tributaries of the internal cerebral veins. PMID- 1589843 TI - The great cardiac vein. AB - The great cardiac vein is the longest venous vessel of the heart; in the majority of our cases it originated at the lower third of the anterior interventricular sulcus (58%). The great and the middle cardiac veins merge at the apex of the heart, forming together with the coronary sinus into which they both empty, a complete venous ring around the left ventricle (13%). On reaching the area of the coronary sulcus, the great cardiac vein crosses the anterior interventricular branch and the circumflex branch of the left coronary artery forming the triangle of Brocq and Mouchet in which the vein is mainly superficial (61%). One, two or three anterior ventricular branches of the left coronary artery traverse this triangle; the relations of the vein and these arteries are very variable and practically unpredictable in 30% of the cases. PMID- 1589844 TI - Mechanisms of orientation of the pelvifemoral base during static loading of the lumbar spine in weight-lifters. AB - Under static loading during weight-lifting, the lumbosacral spine essentially exhibits horizontalisation of the base of the sacrum (superior plateau of S1). We have attempted to elicit the mechanism of this horizontalisation by means of radiographs. These do not demonstrate any movements of the sacroiliac joints or plasticity of the hip bones. However, a symmetrical rotation of the hip joints conditions a retroversion of the pelvic girdle which explains the horizontalisation of the upper sacral plateau. This fixation of the block of the pelvic girdle is under muscular control, so that this mechanism can be improved by appropriate training. PMID- 1589845 TI - Routes of lymphatic drainage from the pancreas: a suggested segmentation. AB - The peripancreatic lymphatics were dissected after intrapancreatic injections of different colorants by territory. The aim of this study was partly to determine the lymphatic drainage routes specific to each pancreatic segment, and partly to define the nodal relay stations for each territory. Whatever the site of injection in the segment of the body and tail, the dye followed the splenic and inferior pancreatic pathways before reaching a left intercelio-mesenteric node (ICMN) and then the supra- and infrarenal nodal groups. However, three distinct drainage routes emerged for the head of the pancreas. The lymphatics of the uncus (anterior and posterior aspects) follow the superior mesenteric route to reach a right ICMN and then the supra- and infrarenal relays bilaterally. Rarely, the lymphatics of the posterior uncus may pass directly to the supra- and infrarenal relays. The anterosuperior segment of the head drains by the gastroduodenal route. This route crosses the superior border of the pancreas and joins the right ICMN. There is an inferior route for this segment which turns back along the inferior border of the isthmus. After injection into the posterosuperior segment of the head, the dye frequently refluxes along the common bile duct and hepatic artery and stains the pericholedochal and hepatic pedicular nodes. When the dye is not entirely collected by these large nodal stations, it goes to join the right ICMN. The right ICMN is the principle relay station for the head of the pancreas. The dye flows only from the pericholedochal relays towards the right ICMN, never in the opposite direction (right ICMN to pericholedochal relays).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589846 TI - Modifications of the skull base in artificial deformations of the circumference of the head. AB - Four artificial deformations of the skull (collection of the Laboratoire d'Anthropologie of the Musee de l'Homme) have been analysed in terms of their morphology and osteometry. The study of the endocranial base in the three planes of space was made possible by a computerised three-dimensional reconstruction based on data gathered by CT. These four skulls were paired as regards their shape (2 annular and dolichocephalic and 2 tabular and brachycephalic) and as regards their age (2 skulls of children and 2 of adults). Certain modifications of the base, such as a tendency to platybasia and to an antero-superior tilt of the posterior fossa around an axis passing through the basion, could be observed in the two modalities of deformation studied. The existence of a region little subject to modelling combining the body of the sphenoid and the basilar and lateral portions of the occiput was confirmed as regards the chondrocranium, whereas the peripheral structures of the base were remodelled like the membranous structures of the vault of the neurocranium. PMID- 1589847 TI - Anatomical rationale for use of the latissimus dorsi flap during the cardiomyoplasty operation. AB - The cardiomyoplasty procedure involves the use of a transformed skeletal muscle to augment cardiac pump function or to substitute for the heart after parietal resection. This study of the intramuscular vascularization of latissimus dorsi was carried out in order to establish the relationship between the dominant thoracodorsal blood supply and the distal supply issued from the intercostal and lumbar arteries. This data is mandatory for the safe manipulation of the muscle flap during cardiomyoplasty. Thirty human latissimus dorsi flaps were carefully studied. We confirmed anatomically as well as angiographically previous macroscopic anatomical reports, as well as the constancy of the neurovascular pedicle. Three principal branching patterns were observed for the thoracodorsal artery. The thoracodorsal artery divides into three main tributaries in 20/30 (67%), and into two tributaries in 10/30 (33%) of the flaps observed. When three tributaries were observed, one of them was a small recurrent artery for the proximal third of the latissimus dorsi (14/20, 70%). Thus the distal vascularization is actually dependent on three principals in 6/30 (20%) and two principals in 24/30 (80%). From these two or three principals emerge several subsequent longitudinal branches (5 to 9) that have a straight course until their distal anastomoses with segmental arterial pedicles issued from intercostal and lumbar arteries. The latter ligation can thus occur without ischemic damage to the medial and distal aspect of the flap. This study emphasizes that, due to macroscopic anatomic features and systematic intramuscular vascular distribution, the latissimus dorsi is probably the most suitable muscle for the purpose of cardiomyoplasty. PMID- 1589848 TI - Anatomic and radiologic bases of surgery of the thoracic aorta. AB - Lesions of the thoracic aorta create problems related to their site and relations with the main aortic branches. The aim of surgery must be to treat the lesion while ensuring perfusion of the tissues excluded by clamping during the operation. Anatomic study of the aortic lesions is based on imaging. Angiography is still often the basic examination though it shows only the lumen and course of the aorta. However, CT and MRI visualise the aortic wall and especially the relations of the aorta to the mediastinal structures. A comparison of anatomic and imaging studies was made on 10 fresh subjects coming from the anatomy department of the Saints-Peres and from the school of surgery of Fer a Moulin. Sections were made every 3 to 5 mm in 3 planes (sagittal, coronal and axial) after CT localisation of the plane of section. This anatomic study was correlated with CT and MR images made on healthy volunteers. The choice of surgical management of a lesion of the thoracic aorta is based on preoperative anatomic assessment by imaging applied not only to the aorta but also to its branches and the territory supplied. PMID- 1589849 TI - The meniscofemoral ligaments: magnetic resonance imaging and anatomic correlations. AB - Examination of the knee joint by magnetic resonance imaging (MRI) is a noninvasive technique of proven reliability as regards lesions of the menisci and ligaments. It provides good definition of the different anatomic structures. The meniscofemoral ligaments have been observed with varying frequency and may be responsible for false images. However, it is important to detect them in cases of hypermobile discoid menisci of the 'Wrisberg ligament type' in order to guide the surgeon in their excision during total meniscectomy. We have attempted to assess the ability of MRI to visualise the meniscofemoral ligaments in correlation with an anatomic study and to identify certain anatomic pitfalls. This study will allow better investigation of the hypermobile menisci associated with the meniscofemoral ligaments. A clinical case is reported to illustrate its practical importance. PMID- 1589851 TI - Reconstruction of an abnormal artery observed in an 11 mm embryo: considerations on the embryologic origin of the subclavian artery. AB - The retro-oesophageal right subclavian a. is a classical variant. We report the first case recognised in the embryo (11 mm subject reconstructed by Born's method). Four other adult cases are analysed (1 dissection and 3 clinical cases) and compared with 250 clinical observations of the supraaortic trunks. In the modal state it arises from the 7th arterial segment. The origin of the subclavian and vertebral aa. and the arrangement of the supraaortic trunks allow the distinction of three types, whose embryologic origin is discussed. PMID- 1589850 TI - Anatomic variations of surgical importance in ethmoid labyrinth and sphenoid sinus. A study of radiological anatomy. AB - The present study was performed on axial and coronal CT scans of 100 patients, most of whom were affected by nasal polyposis. Five observers had to analyse the radiograms and answer a questionnaire including the following items: presence of a supraorbital recess; identification of anterior and posterior ethmoidal canals; dehiscences in the lamina papyracea; pneumatized middle turbinate; presence of a sphenomaxillary plate; presence of Haller's cells; presence of Onodi's cells; relationships of the optic canal; relationships of the internal carotid artery; relationships of the maxillary nerve; relationships of the vidian nerve; level difference between the ethmoid roof and nasal vault; depth of the sphenoethmoidal recess. The data obtained were compared with those drawn from anatomical studies. The fair agreement between them proves the value of CT as an alternative method for studying paranasal sinuses anatomy. PMID- 1589852 TI - Bilateral triple renal arteries in a patient with iliac artery occlusion: a case report. AB - Multiple renal artery abnormalities in a surgical patient with iliac artery occlusion is presented in this case report. Angiographic and operative appearance has been reviewed. We found three renal arteries bilaterally. This abnormality has been compared with the literature and the clinical importance has been emphasized. PMID- 1589853 TI - Anatomical basis of rat brachial plexus reconstruction. PMID- 1589854 TI - Radial and ulnar nerve vascularization in the hand. Anatomic basis of neurocutaneous flap (31.5.91). PMID- 1589855 TI - Herpes zoster ophthalmicus. AB - Herpes zoster ophthalmicus occurs worldwide, usually in healthy adults, but, increasingly in patients who are immunocompromised. After primary varicella infection (chickenpox), the virus lies dormant in the sensory ganglion until it becomes reactivated as zoster. Involvement of the ophthalmic branch of the trigeminal nerve is characterized early by corneal dysesthesia and dendritiform keratopathy, and these are self-limited. However, smoldering disease may cause pathological changes in the ocular structures through direct invasion of virus, secondary inflammation, and alterations of autoimmune mechanisms. Antiviral agents have demonstrated some success in resolving early signs and symptoms, but their role in preventing and treating late complications remains to be fully studied. Until a definitive antiviral agent is established, the benefits of steroid use in certain acute inflammatory processes outweight its risk of reducing host immunity. Corneal complications of herpes zoster ophthalmicus sometimes require surgical intervention. PMID- 1589857 TI - Bilateral visual loss in a child with disc swelling. AB - A nine-year-old girl developed periorbital pain followed by sequential visual loss over a 3-day period. The patient recovered vision to a 20/40 level over a 5 month period of time. The differential diagnosis and evaluation in this presentation is discussed. The patient is believed to have had an idiopathic or parainfectious optic neuritis. PMID- 1589856 TI - Issues in the epidemiology and population-based screening of primary angle closure glaucoma. AB - Among Caucasians, it is well known that 75-95% of primary glaucoma is due to open angle glaucoma (POAG), with angle-closure (PACG) comprising only a very small minority of cases. These figures are reversed among other groups such as Asians and Eskimos, where PACG makes up 80-90% of primary glaucoma. Among Eskimos, the prevalence of PACG has been reported as 2-8%, as compared to 0.1% among Caucasians. It appears that a population tendency toward shallow anterior chambers may explain the excess burden of PACG morbidity. Among Asians, the prevalence of PACG is intermediate between Caucasians and Eskimos. Existing biometrical data do not show a clear tendency toward shallower anterior chambers among Asians. PACG may be screened for on a population basis by means of various techniques that estimate axial or limbal anterior chamber depth, measure intraocular pressure, or evaluate the optic disc or visual fields. Demographic information and medical and family history will also be of great importance in screening for PACG in large populations. Groups at increased risk for the disease include women, individuals over 50, first-degree relatives of PACG probands, and hyperopes. PMID- 1589858 TI - Treatment of metastatic uveal melanoma: review and recommendations. AB - This article reviews the published clinical responses of metastatic uveal melanoma and metastatic cutaneous melanoma with visceral involvement to current therapeutic protocols. Despite isolated patient responses to systemic treatment, no effective treatment currently exists for metastatic uveal melanoma. However, several new approaches involving interferons and interleukin and combination chemotherapy have shown some activity against metastatic cutaneous melanoma. The effectiveness against metastatic uveal melanomas has not been determined. A new approach to intrahepatic administration of chemotherapy also warrants further evaluation because of the high incidence of hepatic involvement with metastatic uveal melanoma. When an effective systemic treatment is found, early administration as an adjuvant to primary treatment may provide the best strategy for control of systemic spread. PMID- 1589859 TI - The optics of fundus examination. AB - It has been 140 years since the invention of the ophthalmoscope in 1851 by Herman von Helmholtz. Since then, a considerable amount of time and effort has been devoted to improving the clinician's view of the fundus both for diagnostic and therapeutic reasons. Recently, there have been some notable advances in this respect, such as the 90 diopter lens, the "2.2 pan retinal" lens, and numerous "wide angle" fundus-viewing contact lenses to which the Volk Quadraspheric fundus lens has been the most recent addition. This paper is a review of the optical principles underlying the methods of fundus examination currently available. PMID- 1589861 TI - Power of a minus lens. PMID- 1589860 TI - An ophthalmologist's journey along uncharted paths. PMID- 1589862 TI - Treatment of angle-closure secondary to ciliochoroidal detachment. PMID- 1589863 TI - [Porcine Epidemic Abortion and Respiratory Syndrome (PEARS)-positive and PEARS negative diagnoses in pig breeding and reproduction farms in The Netherlands using statistical methods]. AB - The diagnoses Porcine Epidemic Abortion and Respiratory Syndrome (PEARS)-positive and PEARS-negative can be made using the following data on herd performance: the average number of stillborn piglets per litter, the average number of live piglets per litter and the average piglet mortality before weaning. Depending on the number of litters used in calculating the averages, the extent to which two out of the three performance data should deviate to arrive at the diagnosis PEARS positive is given in tables and figures. The same farm will only be diagnosed PEARS-negative if after some time at least two out of the three performance data deviate less than other criteria also provided in tables and figures. PMID- 1589864 TI - [Fertility disorders in cats]. PMID- 1589865 TI - [Cows with swollen anus and vulva as a husbandry problem]. AB - An acute farming problem is described. The symptoms were poor intake of concentrates, swelling of the anus and vulva, and decreased milk production. Research results show that pig premix was incorporated into the concentrate for dairy cows. Which component of the concentrate was responsible for the symptoms remains to be established. PMID- 1589866 TI - [Chronic constipation in the adult cat]. PMID- 1589867 TI - [Salmonella enteritidis monitoring and control in poultry in 1991]. PMID- 1589868 TI - Association of blebbing with assembly of cytoskeletal proteins in ATP-depleted EL 4 ascites tumour cells. AB - ATP depletion in EL-4 ascites tumour cells rapidly induced the changes in cell morphology (blebbing), cytoskeletal protein assembly and finally resulted in cell death. After 1 hr of incubation with 2 microM rotenone (inhibitor of respiration) in glucose-free medium, when ATP level was 4% of the initial level, there were increases in triton-insoluble actin and vinculin levels (2.5-fold and 2.8-fold, respectively) and 44% of cells showed blebs; such treatment damaged cells irreversibly. Ca2+ removal did not diminish the effect of ATP depletion on cytoskeleton, blebbing and cell death, although the elevation of free intracellular Ca2+ in rotenone-treated cells was prevented. The role of ATP in maintaining cytoskeleton and cell shape is discussed. PMID- 1589869 TI - Cytokine production from freshly harvested human mononuclear cells attached to plastic beads. AB - The release of tumor necrosis factor (TNF), interleukin-1 beta (IL-1) and granulocyte-macrophage colony-stimulating factor (GM-CSF) from freshly harvested monocytes and lymphocytes attached to plastic beads was investigated. Previous studies had shown that freshly harvested endothelial cells attached to microcarrier beads release an endothelium-derived relaxing factor. Attachment of freshly harvested lymphocytes and monocytes to plastic beads created a dense network, consisting of 25% monocytes and 75% lymphocytes as shown by flow cytometry. Viability of cells was 90%. Monocytes were characterized by phagocytosis and non-specific esterase stain. Freshly harvested cells stimulated with lipoprotein lipase (LPS) released TNF and IL-1. Non-stimulated cells also produced GM-CSF five hours after collection of blood. PMID- 1589870 TI - Effects of insulin, hydrocortisone and prolactin on cell morphology, growth and survival of mammary organoids from mid-pregnant mice cultured on collagen gels. AB - Mammary epithelial organoids consisting of groups of lobular-alveolar acini were prepared from mid-pregnant mice and cultured for 24, 48, 96 and 192 hr on attached collagen gels in the presence of combinations of insulin, hydrocortisone and prolactin. The organoids rapidly attached to the gels and with all the combinations of hormones used colonies of cells spread out as a monolayer from the organoids within 48 hr. Although colony formation continued for up to 192 hr in culture, the maintenance of parental organoid structure after 96 and 192 hr was strongly favoured when hydrocortisone was present in the culture medium. The presence of hydrocortisone produced a dose-dependent increase in the amount of organoid DNA associated with the collagen substratum but decreased the rate of DNA synthesis by the organoids, as measured by the incorporation of labelled thymidine into DNA, in a dose-dependent manner under these conditions. The results suggest that the presence of hydrocortisone minimised the loss of cells from the collagen matrix in these cultures. PMID- 1589871 TI - Quantitative regional variation in the expression of major histocompatibility class II antigens in enterocytes of the mouse small intestine. AB - The qualitative and quantitative expression of major histocompatibility class II antigens was investigated in the absorptive epithelium of the duodenum, jejunum, and ileum from mice of C3H/He (H-2k haplotype) and C57BL/6 (H-2b haplotype) strains by peroxidase-antiperoxidase labelling and image analysis. Immunohistochemical labelling revealed that the expression of class II antigens was greatest in the ileum and decreased proximally towards the duodenum. The villus epithelium of the duodenum showed a granular staining pattern in the apices of some cells. In the jejunum, an increased expression was demonstrated in the apical and basal cytoplasm of all cells covering the villus. Cells at the tip of the villus, in addition, showed staining of the lateral surfaces. Ileal enterocytes demonstrated the most intense immunostaining appearing in the cytoplasm and along baso-lateral surface membranes. Quantitative analyses confirmed that a highly significant (p less than 0.0001) difference in expression of class II antigens occurred in the three regions of the small intestine, which corroborated the qualitative findings. This regional variation of class II molecules by the absorptive epithelium may influence regional differences in antigen presenting functions and immune responsiveness to ingested antigens. PMID- 1589872 TI - Free fatty acids and dialyzed serum alterations of fibroblast populated collagen lattice contraction. AB - Fibroblast populated collagen lattices (FPCL) have facilitated the in vitro study of wound contraction and scar contracture. Mixing fibroblasts, serum containing culture medium and soluble collagen, together and then incubating the mixture at 37 degrees C produces a FPCL. The fibroblasts elongate and spread within the collagen matrix, and by forces associated with cell locomotion they reorganize the collagen fibers. The reorganization of the collagen produces a reduction in size of the FPCL, called lattice contraction. It was also found that dialyzed fetal bovine serum did not support lattice contraction. Supplementing dialyzed serum with fatty acids accelerated lattice contraction. The fatty acid composition of the fibroblast plasma membrane influences that membrane fluidity. These studies demonstrated that lattice contraction was enhanced by the additions of saturated fatty acids in the order of laurate (C-12), palmitic (C-16), and stearate (C-18). With unsaturated fatty acids additions, the order of enhanced lattice contraction was arachidonate (4 C = C), linoleate (2 C = C) and oleate (1 C = C). The addition of dialyzed serum with or without fatty acids neither altered ATP-induced cell contraction activity nor cell proliferation. It was concluded that free fatty acid additions do not modulate FPCL contraction by enhancing microfilaments contraction or increasing cell numbers. The mechanism of action was proposed to be by altering cell membrane fluidity. This finding further supports the theory that the mechanism for lattice contraction is cell locomotion, rather than cell contraction. PMID- 1589873 TI - Conditions for isolation and culture of porcine myogenic satellite cells. AB - Myogenic satellite cells were isolated from semimembranosus muscles of 4-8 week old pigs. Muscles were ground and incubated in 0.8 mg/ml Pronase solution for 40 min at 37 degrees C. Following enzymatic digestion, cells were separated from muscle debris by differential centrifugation and sequential filtering through 500 and 53 microns nylon mesh. Primary cultures grown in 16 mm diameter cell culture wells were used to evaluate five sera, media, and substrata for their ability to promote satellite cell proliferation and differentiation. Porcine satellite cell proliferation and myotube formation were optimized in cultures grown on gelatin coated substratum in the presence of Minimum Essential Medium-alpha supplemented with 10% fetal bovine serum (FBS) (P less than 0.01). Maximum fusion was induced by 48 hr exposure to 2% FBS, horse serum, or lamb serum. These data 1) document the first evidence that myogenic satellite cells can be isolated from porcine skeletal muscle, and 2) identify culture conditions which optimize proliferation and myotube formation of porcine satellite cells. PMID- 1589874 TI - Localization of juvenile hormone esterase during development in normal and in recombinant baculovirus-infected larvae of the moth Trichoplusia ni. AB - The pathogenesis and cellular localization of juvenile hormone esterase (JHE) was examined in larvae of the moth Trichoplusia ni, infected with a recombinant baculovirus (Autographa californica nuclear polyhedrosis virus: AcNPV) engineered to produce high levels of JHE (JHE virus). The course of JHE localization in the recombinant virus infected larvae was compared with that of both wild type AcNPV infected, and uninfected larvae, using immunogold electron microscopy. In the JHE virus infected insects, high levels of JHE were observed in the endoplasmic reticulum of all cells showing evidence of viral structures in the nucleus, except for gut cells which showed only background JHE levels. Tracheole cells and haemocytes appeared to play a role in the dissemination of infection. In uninfected larvae, fat body and epidermis were the major tissues staining for JHE, which was only detectable at peak times of JHE activity during the fifth instar: lower levels at other times could not be distinguished from background. JHE was also present in lysosomes of granular haemocytes: these lysosomes increased in number in the fifth instar compared to the fourth instar. Similar lysosome-like granules in the pericardial cells did not become highly positive for JHE antigen until the fifth instar. PMID- 1589875 TI - The Sertoli cell membrane body in the skink. AB - The structure of the Sertoli cell and its physical relationship with the germ cells was studied in laboratory maintained skinks, Eumeces laticeps (Schneider) in January, and September, corresponding to the periods of prenuptial and postnuptial spermatogenesis respectively. Light micrographs obtained using 1 micron thick plastic sections, show the Sertoli cell to have a large polymorphic nucleus located in the basal portion of the cell, and a darkly staining juxtanuclear body. In ultrathin sections, this body consists of a complex array of thin, electron dense membranous structures resembling the endoplasmic reticulum. The lumina of these membranous channels appear empty. Between the channels, there are structures that resemble the expanded cisternae of the endoplasmic reticulum. In some sections, these dilated cisternae are confluent with the channels, indicating that the channels and the cisternae are parts of the same structure. Three organelles, namely, mitochondria, lysosomes and microfilaments are found among the elements of the membrane body. There is no structural modification of the channels where they come in contact with mitochondria, but they are dilated in proximity to lysosomes. In some sections bundles of microfilaments are clearly visible within the diamond shaped region of contact between two channels, suggesting that these organelles are involved in structural or functional organization of the membrane body. PMID- 1589876 TI - Structural domains of the tight junctional intramembrane fibrils. AB - Freeze-fracture reveals intramembrane fibrils lying along the intermembrane contacts that characterize tight junctions. Tight junctions from a variety of species are reexamined here by rapid freezing prior to freeze-fracture. The tight junction fibril is uprooted alternatively from either the cytoplasmic or the exoplasmic hemibilayer during freeze-cleavage, exposing two distinct but complementary views of its hybrid structure within the same replica. When the transmembrane fibril is uprooted from the exoplasmic hemibilayer it appears on the P-fracture face as a smooth-surfaced cylinder which is sometimes resolved into periodic globular structures. The lack of indication that the P-face cylinder has been pulled out through the opposite membrane half indicates that this domain of the fibril is, in large part, buried in the hydrophobic interior of the membrane. However, when the transmembrane fibril is uprooted from the cytosolic hemibilayer it appears on the E-fracture face as a row of irregular intramembrane particles. The irregular particles on the E-face aspect of the fibril are interpreted as corresponding to transmembrane protein segments that may very well make projections onto the cytosolic surface of the bilayer. En face views of the outermost junction strand between adjacent epithelial cells show periodic lines on the bilayer on each side of the junction which are interpreted as periodic transmembrane protein segments arising from the core structure of the tight junction fibril. If the backbone of the tight junction strand is an inverted cylindrical micelle, it must typically include proteins, which might anchor it to structures outside the membrane bilayer. PMID- 1589877 TI - The carcinogenicity of ciclosporin. AB - Experimental data relevant for the evaluation of the carcinogenic potential of the immunosuppressant ciclosporin are reviewed: Firstly, the mode of action of ciclosporin at the level of lymphocyte gene transcription, secondly, the main adverse effects especially nephrotoxicity and thirdly, the results of the chronic bioassays. The experimental data are discussed together with the clinical evidence of increased incidence of tumors, especially lymphoproliferative disorders under ciclosporin immunosuppression. Conventional immunosuppression (azathioprine, anti-lymphocyte globulin, prednisone) also demonstrates comparable risks to develop tumors. Lympho-proliferative lesions regress after dose reduction or cessation of treatment. Furthermore, combinations of various immunosuppressants may result in a higher incidence of viral infection and malignancy. In summary, chemical immunosuppression carries the intrinsic risk of tumor growth. In the case of ciclosporin, which has no direct genotoxic effect, tumor promotion is probably dose-dependent. Thus, the risk may be reduced by low dosage and by avoiding combination therapies with additional immunosuppressants. PMID- 1589878 TI - Role of aluminium in skin reactions after diphtheria-tetanus-pertussis poliomyelitis vaccination: an experimental study in rabbits. AB - The occurrence of subcutaneous nodules at the injection site is one of the complications of diphtheria-tetanus-pertussis-poliomyelitis vaccination, but the causes and mechanisms involved are still poorly understood. An experimental study in the New Zealand rabbit enabled us to determine the frequency of occurrence of these nodules, how long they persist and the histopathologic features of the cells involved. Aluminium (Al) assays by electrothermal atomic absorption spectrometry allowed us to study concentrations both in nodules and the organism (serum, normal skin). The results show an absence of Al diffusion outside nodules, a correlation between infiltrate intensity and Al concentration in nodules and modifications in the histological constituents of nodule cells. The histological picture indicates a foreign body reaction to Al. All these data underscore the role of Al in the formation of early postvaccinal nodules at the injection site. PMID- 1589879 TI - Comparative study on the toxicity of methyl linoleate-9,10-ozonide and cumene hydroperoxide to alveolar macrophages. AB - In the present study the in vitro toxicities of methyl linoleate-9,10-ozonide (MLO) and cumene hydroperoxide (CumOOH), a model peroxidative agent, are compared. This was carried out using the inhibition of alveolar macrophage phagocytosis as an assessment of in vitro toxicity. Both agents, MLO and CumOOH caused a dose-dependent decrease in the phagocytosing activity of alveolar macrophages isolated from rat lungs. MLO was found to be three times more toxic than CumOOH. Supplementation of macrophages with vitamin C resulted in a decrease of their sensitivity towards MLO and an increase of their sensitivity towards CumOOH, suggesting that different mechanisms underlie the toxic effects of the compounds concerned. This was supported by the data on GSH and vitamin E depletion. In both cases, depletion of the antioxidant was more extensive on exposure to CumOOH. In addition, following GSH depletion, the sensitivity of the macrophages towards CumOOH was more increased than towards MLO. Further, MLO was not able to enhance the peroxide formation from methyl linoleate (ML), whereas CumOOH initiated the peroxide formation of ML. The results of ESR spin trap experiments further supported that MLO-induced toxicity is independent of lipid peroxidation. From all this it is concluded that both mechanisms known to be of importance for peroxide-induced cell toxicity, i.e., depletion of cellular GSH levels and/or lipid peroxidation are not the main processes causing MLO toxicity in vitro. PMID- 1589880 TI - Toxicity of 2,3,7,8-tetrabromodibenzo-p-dioxin in rats after single oral administration. AB - Five male and female rats per dose-group received 2,3,7,8-tetrabromodibenzo-p dioxin (2,3,7,8-TBDD) once on the first day of the study. Doses of 10, 33, 100, or 300 micrograms 2,3,7,8-TBDD/kg body wt. and the vehicle control were administered by gavage. About 20% of 2,3,7,8-TBDD was excreted via feces. Severe body weight retardation was observed in the 100 and 300 micrograms/kg dose groups. Most animals in the 300 micrograms/kg dose-group and the females receiving 100 micrograms/kg showed emaciation, rough coat and a poor health (wasting syndrome). Of the animals dosed with 300 micrograms/kg, 3 males and all females died. After 100 micrograms 2,3,7,8-TBDD/kg 3 females died. Measured 4 weeks after dosing, triiodothyronine (T3) was increased and thyroxin (T4) was reduced dose dependently in serum. A dose-dependent decrease in thymus weights was observed at necropsy and histological examinations showed that thymus and spleen were depleted of mature lymphocytes. An increase in liver-to-body weight ratio was observed in all dose-groups. The histological examination revealed hypertrophy of centrilobular hepatocytes in the liver of animals treated with 100 micrograms/kg, which was less severe at the 33 micrograms/kg dose. Hypertrophic hepatocytes were also detected in some animals at the lowest dose. Induction of enzyme activities of the mixed function oxidases ethoxycoumarin O-deethylase (ECOD), ethoxyresorufin O-deethylase (EROD) and aryl hydrocarbon hydroxylase (AHH) in liver tissue differed for each of the three enzymes. Two days after administration, enzyme activities were increased but did not differ substantially between dose-groups. Twenty-eight days after dosing the increase in activity after 10 micrograms/kg was largest and the EROD of the 100 micrograms/kg dose group in females was close to that of the control. This inverse dose-response relationship may be due to impaired liver cell function at higher doses. PMID- 1589881 TI - Susceptible period for the teratogenicity of di-n-butyltin dichloride in rats. AB - Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 20 mg/kg on days 7-9, 10-12 or 13-15 of pregnancy or at a dose of 20 or 40 mg/kg on day 6, 7, 8 or 9 of pregnancy. While treatment with DBT on days 7-9 was significantly and highly teratogenic, no evidence of teratogenicity was detected when DBT was given on days 10-12 or 13-15. Treatment on day 7 or 8 with both doses of DBT, but neither on day 6 or 9, resulted in an increased incidence of fetuses with malformations. The highest incidence of malformed fetuses occurred after treatment on day 8. The incidence of malformed fetuses was proportional to the dose of DBT. Anomaly of tail, anal atresia, club foot, omphalocele, deformity of the vertebral column, defect of the ribs and anophthalmia or microphthalmia were predominantly observed. It could be concluded that, following maternal exposure to DBT in rats, developing offspring are not susceptible to teratogenic effects of DBT on day 6 and that day 7 is the earliest susceptible period, day 8 is the highest susceptible period and day 9 is no longer a susceptible period for teratogenesis of DBT. PMID- 1589882 TI - Stimulative effects of cadmium on bone resorption in neonatal parietal bone resorption. AB - Effects of cadmium on bone resorption were investigated using neonatal mouse parietal bone culture system. Cadmium at 0.5 microM and above stimulated hydroxyproline release as well as 45Ca release. As cadmium-stimulated bone resorption was inhibited by calcitonin, bone resorption induced by cadmium is osteoclast-mediated bone resorption. CI-1, collagenase inhibitor, depressed cadmium-stimulated bone resorption in a dose-dependent manner. Osteoblasts are also involved in cadmium-induced bone resorption. Indomethacin-inhibited cadmium stimulated bone resorption and cadmium-treated bones released prostaglandin E2 to a greater extent than untreated bones. Cadmium-stimulated bone resorption was shown to be dependent on the production of prostaglandin E2. 3-Isobutyl-1 methylxanthine potentiated cadmium-stimulated bone resorption and verapamil depressed it. It is possible that an increase in levels of cAMP and calcium ion in bone cells is involved in cadmium-induced bone resorption. From these results, cadmium was found to stimulate osteoclast-mediated bone resorption which is dependent on prostaglandin E2. Second messengers in cadmium-induced bone resorption may be cAMP and calcium ion. PMID- 1589884 TI - [The structure of the conclusions in the forensic medical expertise of material evidence]. AB - A new structure of conclusions including special chapter "Conclusion validity", which ensures their high availability for officials of legal investigation agencies is suggested. The examples of conclusion making on the basis of new form in case of blood, secretion and hair tests performed in two variants (known and unknown criminal) are presented. PMID- 1589883 TI - [Human genotyposcopy: the identification of the species, sex and individual by DNA genetic imprints in a case connected with a murder attempt]. AB - Blood stains on a knife were identified by DNA genotyposcopy. The statistical validation method has confirmed that the blood stains on material evidence belonged to the victim, the probability of random coincidence being less than 10( 11). The efficacy of using hypervariable locus-specific DNA probes and the possibility of detecting DNA impressions in blood stains stored for more than 3 months have been demonstrated. PMID- 1589885 TI - [The HLA system and its significance in the expertise of doubtful paternity]. PMID- 1589886 TI - [The use of derivative spectrophotometry for the identification of drug and narcotic substances extracted from biological objects]. PMID- 1589887 TI - [Optimization of the conditions for extracting metronidazole with organic solvents]. AB - Optimal conditions of metronidazole extraction from aqueous solutions by different solvents using a mathematical method of experiment planning (latin square) were studied. It was stated that optimal conditions of metronidazole extraction from aqueous solutions were: extraction time (5 min.), pH medium-6, extractant-isoamyl spirit in saturation of aqueous phase with ammonium sulfate. PMID- 1589888 TI - [The detection of abortion agents in biological material]. AB - Methods of extraction and detection of ascorbic acid, ergot alkaloids, cotarnine, microfollin, tinctures of marigold, peony, sage-brush, iodine, benzestrol, pachycarpine, hexestrol, folliculin, quinine, ethoxydiaminoacridine lactate were developed. Detection limits are 0.1-1 mg/100 g of object. Methods of manganese, iodine and soap detection are developed. Detection limits are 0.05-2 mg/100 g of object. PMID- 1589889 TI - [The detection of aromatic substances in biological material]. AB - The author presents experimental data and suggests a method for extraction of aromatic substances from the blood, urine, lavage water, stomach and its contents, liver and kidneys. The extract is dissolved in 96% ethanol and the aromatic substances are detected in reactions with hydrochloric acid, Marki's reagent, 2,4-dinitrophenylhydrazine, diazotized o-dianisidine, phthivazide, chromotropic acid by UV spectrophotometry, thin-layer and gas-liquid chromatography. The sensitivity of the method is 0.1-0.5 mg %. PMID- 1589890 TI - [The establishment of the features of the blade of a stabbing-cutting weapon by the damages to human skin and to tricot clothing]. AB - Presents forensic medical characteristics of the specific features of stabbed and cut injuries of human skin and jersey. Suggests a complex of signs that will help determine some structural parameters of a knife blade and the conditions of its interaction with the injured site of human body. PMID- 1589891 TI - [A method for determining arsenic in biological material]. AB - Method of extraction-atomic absorption detection of arsenic in biologic material using naphthenic acid was developed and tested. Method can be used for arsenic detection in postmortem material. It differs from the known method by its accuracy, reliability and simple use. PMID- 1589892 TI - [The use of gel chromatography for purifying ergometrine in the analysis of biological material]. PMID- 1589893 TI - [The forensic chemical determination of remantadine in biological material]. AB - Suggests new microcrystalloscopic tests for the identification of remantadine and assesses the specificity and sensitivity of these tests. Describes a thin-layer chromatographic technique for remantadine identification. PMID- 1589894 TI - [The forensic medical determination of the intravital or postmortem origin of injuries]. PMID- 1589895 TI - [The forensic medical and clinico-morphological aspects of the study of skin scars]. PMID- 1589896 TI - [The morphological changes in the central nervous system in the early periods after craniocerebral trauma]. PMID- 1589897 TI - [The traumatic detachment of parts of the body in automobile injury]. PMID- 1589898 TI - [A complex method for determining age by tooth status using analog computers]. AB - Combination of roentgenography with direct image magnification and its analysis by medical iconics methods increase significantly possibility of age determination by teeth status (prediction accuracy by upper canine tooth is 99.8% +/- 0.81 year). Adaptive character of change in teeth density over the period of their functioning was detected. Integrative metric index--age metric index--is an objective criterion of age status of a tooth. PMID- 1589899 TI - [Epidemic of chronic diseases]. PMID- 1589900 TI - [Alzheimer's disease: variety without unity]. AB - The diagnosis of Alzheimer's Disease is quite common these days. Nonetheless, a clearcut definition of the concept of Alzheimer's Disease is still beyond scientific reach. This discrepancy makes it particularly relevant to explore the meanings of the concept, and to ask some questions concerning how diseases are defined. Alzheimer's Disease has been introduced into nosology by Kraepelin, at the beginning of the 20th century. Kraepelin's claim that Alzheimer's Disease is a disease sui generis, was contested promptly: by Alzheimer himself, for instance. This initiated a history of intensive debate concerning the distinction between Alzheimer's Disease and Senile Dementia on the one hand, and the distinction between Senile Dementia and ageing on the other. During the 1970s and 1980s, several important changes took place, which elucidated the use of clinical and neuropathological criteria for the diagnosis of dementia and Alzheimer's Disease. This, however, did not end the debate. A definite criterion--a gold standard--for the diagnosis of Alzheimer's Disease is still lacking. Recent developments in the field of molecular biology furthered the insights into the pathological processes in Alzheimer's Disease. These developments show that a unitary definition of Alzheimer's Disease (including the presenile and senile forms) is not to be expected. There are therefore insufficient reasons to accept a disease entity called 'Alzheimer's Disease'. In this sense we are not far removed from Alzheimer's and Kraepelin's days. The interpretation--both in- and outside science--of Alzheimer's Disease as an entity is therefore not supported by sound scientific arguments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589901 TI - [Norton's decubitus risk score in a nursing home]. AB - Decubitus must be considered an important problem in public health care. In the Netherlands (total population 15 million) the costs of prevention and treatment of decubitus in the hospitals and nursing homes are approximately Dfl. 700 million per year. In order to identify patients at risk for the development of decubitus at an early stage. Norton and colleagues developed a scoring system that includes an assessment of general physical condition, mental status, activity level, mobility and incontinence. In a prospective study in 224 somatic nursing home patients we investigated the relationship between the Norton-score and the appearance of decubitus. The authors conclude that, when using the Norton score, it is not possible to differentiate patients at risk clearly from patients with no risk. From the five items used by Norton, only mobility and, to a lesser degree, general physical condition, show a significant relation with the occurrence of decubitus ulcers. In order to identify the patients at risk roughly, the physician can suffice with scoring these two items. PMID- 1589902 TI - [Rehabilitation of nursing home patients with a leg amputation. A retrospective study]. AB - In order to assess the effect of rehabilitation of lower-extremity amputees in a nursing home, a retrospective study was conducted. The results were compared with existing Dutch data. Moreover, the influence of several selected factors on the results of rehabilitation was assessed. The study covered a period of five years and concerned 61 patients admitted with a lower-extremity amputation. Their median age was 73 (range 38-91) years. After rehabilitation two-thirds of the patients were able to walk with an ambulatory aid and five without; a quarter came to depend on a wheelchair. Return to home or sheltered housing was possible for almost three-quarters of the patients. Only one out of eight selected factors was in this study of influence on the results of rehabilitation i.e. motivation. PMID- 1589903 TI - [Institutional care for the aged in the 2d half of the 19th century. A case study]. AB - This study focuses on the residents of three ecclesiastical homes for the elderly in 19th century. The Hague. These homes took in poor members of the church who were at least 60 years old. Most of the elderly who resided in these homes had received poor relief prior to admission. The main reason to request admission was that they were no longer able to independently run a household. Most of the residents were well past the age of 60 upon entering the home, women generally being a few years older than men. There were no significant gender differences in duration of residence. The female age at death was a few years higher than for males. The health of the residents appeared to be worse than that of the total elderly population of The Hague, resulting in a higher death rate. In general, residents had independently run a household prior to admission. PMID- 1589904 TI - Pathogenesis of NSAID gastropathy: are neutrophils the culprits? PMID- 1589905 TI - Alzheimer's disease: pathology to potential treatments? PMID- 1589906 TI - This and that: sequential theories for stomach cancer and the multiple applications of isotopic ratios. PMID- 1589907 TI - The 5-HT4 receptor: a place in the sun. PMID- 1589908 TI - Therapeutic potential of cytokine manipulation. AB - Interleukin 1 is just one of a large, growing, collection of potent cytokines that are produced by a variety of cells and have a myriad of overlapping activities. Many of these cytokines have important pathophysiological actions in diseases ranging from rheumatoid arthritis to AIDS. Selective inhibition of the synthesis or of the action of specific cytokines may have therapeutic benefit. In this review, Brian Henderson and Simon Blake discuss the ways in which cytokine function could be manipulated pharmacologically for therapeutic benefit. PMID- 1589909 TI - A subfamily of 5-HT1D receptor genes. AB - The recent discovery and characterization of three new 5-HT1 receptor clones and the pharmacological characterization of one orphan receptor (dog RDC4) has revealed a surprising complexity within the 5-HT1D receptor subfamily. This receptor subfamily, which is believed to be the target of the anti-migraine drug sumatriptan and may regulate feeding behavior, anxiety, depression, cardiac function and movement, can now be approached on a molecular level. These cloning discoveries have also taught us an important general lesson about the molecular pharmacology of G protein-coupled receptor genes: species homologues of a gene (the equivalent gene in different species) may be highly homologous in amino acid sequence yet display very different pharmacological properties. Conversely, two different genes in the same species (intraspecies subtypes) that display only moderate degrees of transmembrane amino acid homology can display nearly indistinguishable pharmacological properties. In discussing the implications of these findings for both 5-HT receptors and G protein-linked receptors in general, Paul Hartig, Theresa Branchek and Richard Weinshank approach the question: why have so many receptor subtypes been preserved in the genome? In addition, controversy has been raging for several years over the classification of 5-HT1B receptors (found only in rat brain) and 5-HT1D receptors. Were they different subtypes or simply species homologues of the same receptor? Recent cloning studies have apparently complicated this issue, but the answer to the question is, in fact, becoming clearer. PMID- 1589911 TI - Grading and prognostic significance of urologic carcinomas. AB - The extent of surgical therapy of urological tumors and the intensity of post surgical or primary chemo- or radiotherapy are dependent on staging and grading. Since the proliferative activity determines the size of the tumor, the primary prognostic evaluation corresponds with the grading. The histologic, cytologic, immunohistochemical and cell kinetic methods of examinating urological tumors are discussed considering their significance. Two tumor subgroups of malignancy are differentiated, one with a low risk and one with a high risk. The tumor group of intermediate malignancy (G II) consists of a mixture of both prognostic groups. Possibilities of an easy-to-use subgrading are given in order to differentiate a particular group from other subgroups at risk. A clear distinction between two subgroups of urologic tumors, namely with high or low malignancy, is a presupposition for the successful application of a differentiated therapy nowadays. Prognostic studies have corroborated this tumor subdivision. PMID- 1589910 TI - Of mice and flies: commonalities among 5-HT receptors. AB - Pharmacological studies as well as molecular cloning of 5-HT receptors have revealed a multiplicity of receptor subtypes, not only in mammals but, as discussed in this review by Rene Hen, also in molluscs and arthropods. Most of these receptors belong to the G protein-coupled receptor family, and their mechanism of action involves modulating levels of second messengers such as cAMP, IP3 and Ca2+. Rather than being specialized in a particular physiological function, a given receptor may be expressed in multiple neurons throughout the brain but always in the same compartment in these neurons. The 5-HT1B receptor, for example, is generally localized presynaptically on neuronal terminals, where it inhibits neurotransmitter release. A widespread distribution of 5-HT receptors might explain how 5-HT can modulate the multiple neuronal circuits that underlie complex behaviours. PMID- 1589912 TI - Cytogenetic evidence of gene amplification in urothelial cancer--a possible mechanism of tumor invasiveness. AB - A cytogenetically detectable form of gene amplification, presumably oncogene amplification, double minute chromosomes, has been found in 11 out of 45 specimens (24%) of moderately and poorly differentiated, deeply infiltrating transitional cell carcinoma of the bladder and ureter. None of the 75 low-grade low-stage tumors contained this karyotypic anomaly. It is obvious that double minutes are not a rare and sporadic phenomenon in this type of tumors; additionally there is strong evidence that they are involved in tumor progression, i.e. they are associated with tumor aggressiveness and unfavorable prognosis. PMID- 1589913 TI - Epidermal growth factor in urine from the patients with urothelial tumors. AB - Epidermal growth factor (EGF) concentration in urine was measured with a radioimmunoassay in 40 untreated patients with urothelial tumors and a comparable control group of 25 normals. The concentration of EGF in urine from the patients with bladder, renal pelvic or ureter tumors was lower than normal (p less than 0.05). Patients with T4 tumors had lower concentrations of EGF compared with those of other stages. EGF concentrations after transurethral resection of bladder tumors were significantly elevated compared with the values before operation. These findings suggest that urothelial tumors are related to a low concentration of EGF and that a decrease of EGF is associated with invasion of tumors. PMID- 1589914 TI - DNA ploidy, S-phase fraction and cytomorphometry in relation to survival of human penile cancer. AB - The prognostic significance of DNA ploidy, DNA index, S-phase fraction (SPF) and median nuclear size was studied in 11 patients with squamous cell carcinoma of the penis. These patients have been followed for a minimum of 7 months after diagnosis. Nuclear DNA content was determined by flow cytometry from paraffin embedded tissue. Patients with DNA diploid cancer (n = 7, 64%) had a better survival rate than patients with aneuploid cancer, and a small SPF was associated with a favorable outcome. A statistically significant relation between median nuclear size and survival could be demonstrated. Small modal nuclear size associated with poorer prognosis. There was a significant difference in survival between metastatic and nonmetastatic groups of tumors during the follow-up period. This study suggests that flow cytometric determination of nuclear DNA ploidy from paraffin-embedded samples in penile cancer does add an additional prognostic determinant in addition to the clinical staging of tumors. PMID- 1589915 TI - Intravesical therapy with adriamycin plus verapamil in patients with superficial bladder cancer: a pilot study. AB - Nineteen patients with histologically proven superficial bladder cancer (Ta, T1) were treated with intravesical instillation of 30 mg of adriamycin (ADM) dissolved in 24 ml physiological saline plus 15 mg of verapamil (VR) (6 ml) every day for 10 days. In spite of the short period of treatment, 6 of the 18 evaluable patients (33.3%) showed complete response (CR) and a further 5 (27.8%) showed partial response (PR). Five of the 6 patients with CR were recurrent cases who had previously received prophylactic intravesical instillation chemotherapy including ADM. Irritative urinary symptoms were observed in 11 of the 19 patients (57.9%). However, these symptoms were mild in the majority of patients and the treatment was completed without interruption in all but 1 patient. There was no significant absorption of ADM and VR into the systemic circulation. No clinical evidence of systemic toxicity was observed. These results suggest that combination of ADM and VR has a possibility to be a useful prophylactic intravesical instillation chemotherapy after endoscopic resection of not only primary but also recurrent chemoresistant bladder cancers. PMID- 1589917 TI - Topological localization of the frequency and amplitude characteristics of the whole and segmented renal pelvis. AB - The contractile characteristics of pacemaker regions in the unicalyceal renal pelvis of the rabbit were examined in vitro. The amplitude and frequency spectra of spontaneous contractions of whole and separated circular and longitudinal renal pelvic strips were identified. The effect of stretch on these parameters were examined in order to establish whether the pacemaker region that generates contractions in the renal pelvis was sensitive to distention. The results show that the frequency of spontaneous contractions in the whole pelvis (65 +/- 18 mHz) was significantly higher than any part of the circularly (41 x 8 mHz) or longitudinally cut (43 +/- 8 mHz) pelvis. The amplitude of longitudinal strips, 52 +/- 11 mg, was significantly smaller than that of the circular strips, 267 +/- 52 mg. In the circularly separated pelvis the frequency of spontaneous contractions was highest in the proximal part (41 +/- 8 mHz) and lowest in the pelviureteral junction (8 +/- 1 mHz). No significant increase in frequency was seen upon stretch in the whole or separated pelvis although there was a decrease in the amplitude of both the whole and separated pelvis. These results show that the frequency of contraction of the whole or the segmented renal pelvis is not sensitive to stretch. PMID- 1589916 TI - Ureterocalicostomy in the treatment of pyeloplasty failures. AB - Ureterocalicostomy was performed in 8 patients following failed pyeloplasty: 2 had undergone two previous pyeloplasties, while endourological management had been attempted in 3. With a mean follow-up of 58.7 months, radiographic studies demonstrated resolution of the obstruction in 6 cases (75%), while two kidneys lost their function. The definitive role of endourological techniques after pyeloplasty failure still waits the test of time although they deserve to be applied first, and ureterocalicostomy remains a reliable procedure in this particular setting. PMID- 1589918 TI - Renal pelvic pressure isolation from active and passive bladder pressures in the rat: the facilitating effect of urine flow rate. AB - The circumstances facilitating hydrostatic pressure communication between the bladder and renal pelvis were evaluated. In particular, we compared active detrusor contractions occurring spontaneously during voiding and evoked contractions produced during electrical pelvic nerve stimulation with passive abdominal compression. These variables were evaluated with respect to urine flow rate and bladder capacity. Waveform analysis of the pacemaker characteristics of the renal pelvis shows that the rat pelvis has a narrow frequency band of spontaneous contraction at 0.5 +/- 0.06 Hz. The baseline waveform and pressure of the pelvis is effected by urine flow and bladder capacity. Significant elevations in pelvic pressure of 25.8 +/- 7.9 and 28.7 +/- 5.8 cm H2O were observed for bladder pressures of 30 cm H2O (n = 8) at flow rates in the range of 2.5-5.0 and over 5.0 ml/kg/h respectively (p less than 0.05). At flow rates between 2.5 and 5.0 ml/kg/h, spontaneous contractions produced an increase in pelvic pressure in all rats, while electrical stimulation produced an increase in pelvic pressure in 63%. At flow rates above 5 ml/kg/h, abdominal compression produced sharp elevations in pelvic pressure in 75%. At the same flow rate, electrical stimulation produced a slow increase in 75% and spontaneous contraction produced a slow increase in 86%. These results suggest that the exposure of the upper urinary tract to vesical pressures occurring during active and passive contractions is facilitated by flow. PMID- 1589919 TI - Pharmacologic effect of thiphenamil HCl on lower urinary tract function of healthy asymptomatic volunteers. AB - The effect of thiphenamil HCl on the urodynamic parameters of bladder filling, voiding and isometric contraction was examined in controls. Data were obtained from 25 control female subjects with a mean age of 27.6 +/- 6.6 years. Three urodynamic studies were done on each subject on 3 different days. These studies were: (1) control study, (2) drug study with a single oral dose of 400 mg thiphenamil HCl and (3) another with 800 mg. Each urodynamic study involved filling and voiding cystometrograms to characterize stability, sensations of fullness and urgency, bladder capacity, urethral opening pressure, maximum flow rate, maximum detrusor pressure and residual urine. In addition, isometric detrusor pressure measurements were made at bladder volume increments of 100 ml. Each urodynamic study was done in the sitting position using medium fill water cystometry at 20 ml/min. Isometric pressures were made by catheterizing the subject with an 18-french three-way Foley catheter with a 30-ml balloon. One lumen was used to fill the bladder and the second to measure pressure. The results show that bladder capacity and the volume at which sensations of fullness and urgency are expressed are not significantly changed under the influence of thiphenamil HCl. Significant differences were seen in the maximum pressure generated by the detrusor during voiding and in the maximum urine flow rate. These differences were most pronounced at the 800-mg thiphenamil HCl dose. The isometric data show a highly significant increase in the maximum isometric pressure developed at the low bladder volumes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589920 TI - Are sensations perceived during bladder filling reproducible during cystometry? AB - We evaluated whether sensations recorded during a medium-fill cystometry are reproducible. In 10 patients, the evaluation was done during two successive bladder distentions. In 95 patients, the results of a sensory evaluation during urodynamic tests with a mean interval of 15 months were compared. An identity of sensations was reported by 80% of the patients in the short-term study and by 73% of the patients in the long-term study. The perception of a first sensation of filling was the most variable. PMID- 1589921 TI - Rectourethral reflex: description of a reflex and its clinical significance. A preliminary report. AB - The present communication studies the technique and clinical significance of a new reflex which I called 'rectourethral reflex'. The study comprised 29 subjects with normal anorectal and urinary functions. The procedure consisted of inflating the rectum with a balloon connected to the distal part of a catheter. The electromyographic activity of the external urethral sphincter was recorded using a concentric needle electrode inserted into the muscle. The procedure was repeated in 10 patients after muscle infiltration with Xylocaine or saline. Rectal distension evoked external urethral sphincter contraction in all the subjects. The amplitude of motor action potentials increased with increasing rectal distension. Anesthetized muscles did not respond, while saline-infiltrated muscles responded. The latency of the reflex decreased with increasing volume of rectal inflation. The reflex harmonizes the relation between defecation and micturition. It guards against involuntary micturition when the rectal detrusor is distended. Changes in amplitude and latency of the reflex may be significant in assessing rectourinary disorders. The reflex could thus be used as an investigative tool in the diagnosis of such disorders. PMID- 1589922 TI - Prediction of postoperative retention in elderly patients undergoing nonprostatic surgery by preoperative uroflowmetry. AB - 500 patients above 50 years of age, undergoing lower abdominal/perineal surgery and having no urinary complaints were assessed by measuring the preoperative maximum flow rate (Qmax). They were subsequently observed for urinary retention in the postoperative period. The analysis of the results has shown a definite relation between the preoperative Qmax and the probability of urinary retention in the postoperative period and uroflowmetry has been found to be a good screening procedure for the detection of cases which could possibly have urinary trouble requiring significant intervention in the postoperative phase, thereby changing the priority of surgical attention. PMID- 1589923 TI - Maximum flow rate-guided dilatation in patients of stricture urethra: a controlled study. AB - Maximum flow rate (MFR) is an objective uroflowmetric parameter for assessment of urethral stricture. Its use as a guide to assess the frequency of dilatation of the urethra on an outdoor basis could make the approach very scientific and objective. 70 cases were evaluated in two groups, study and control, each of 35 patients. Dilatation in the study group was guided by serial measurement of MFR, while in the control group, stricture was dilated on a traditional scale. A comparison between the two groups showed a statistically significant decline in the frequency of dilatation in the study group. A routine practice of MFR-guided dilatation in stricture clinics is recommended by us. PMID- 1589924 TI - Anterior urethroplasty--changing concepts. AB - The management of complex anterior urethral strictures, not amendable to dilatation or internal urethromotomy, is difficult. Our experience of treating long strictures of anterior urethra with one-stage urethroplasty in 16 cases and two-stage Johanson's in 12 cases are reviewed here. The strictures had varied etiology and many were associated with fistula, diverticulum, etc. Three cases had concomitant posterior urethral strictures and were managed by one-stage anterior and posterior urethroplasty simultaneously. The one-stage repair was done using vascularized flap of longitudinal ventral penile skin in most cases. Transverse scrotal flap and Duckket's transverse preputial flap were utilized in 2 cases each. In one-stage repair success was 100% and in two-stage repair it was 75%. Our preference is now for one-stage repair irrespective of length and number of strictures. PMID- 1589925 TI - Assessment of voiding dysfunction in men with acute epididymitis. AB - Fifteen men with a recent attack of acute epididymitis were examined urodynamically and endoscopically after the symptoms had resolved. Thirteen of the 15 patients had abnormal voiding. Two patients had stricture formation in the posterior urethra, one had benign prostatic hyperplasia, one had bladder neck sclerosis, and 4 had detrusor-external sphincter dyssynergia. Three patients including the one with prostatic enlargement presented abdominal straining exceeding 50 cm H2O during micturition. The cause of an obstructive voiding pattern could not be established in 3 patients. The results support the theory of urethrovasal reflux due to a high hydrostatic pressure at the collicular level as a pathophysiological factor in acute epididymitis. PMID- 1589926 TI - Ultrasonographic findings in patients with nonbacterial prostatitis. AB - The potential value of prostatic imaging in the diagnosis of inflammatory disorders of the prostate is largely unexplored. In several studies, specific ultrasonographic characteristics in patients with prostatitis have been described. Also nonspecific echogenic qualities in prostatitis have been pointed out. To evaluate ultrasound of the prostate in patients with nonbacterial prostatitis in this study, ultrasound images of these patients were compared with those of a healthy control group. In contrast with earlier findings, constant dilatation of the periprostatic venous plexus was seen more pronounced in the control group as well as elongation of the seminal vesicles. Finally, prostatic calcifications were frequently encountered in both groups. PMID- 1589927 TI - Long-term results of varicocelectomy. AB - Between 1983 and 1985, 257 infertile men were examined for any present varicocele by means of the Doppler sonography, telethermography and palpation. Based on these findings, the spermiogram and the infertility history, high ligation of the spermatic vein was indicated in 89 patients with varicocele and a median duration of infertility of 36 months (6-88 months). Postoperative sperm examinations have shown a significant improvement in sperm count and morphology, but not in motility. The most significant drop was observed in germ cell concentration from 1.68 to 1.06 mio/ml (p less than 0.025 Wilcoxon signed rank sum test). The follow up examination 6 years after the beginning of the study has shown that only 56 out of the 89 patients underwent surgery, whereas 33 patients refrained from it. Pregnancy rates were 42% (23 out of 55, 1 patient lost to follow-up) in the operated group and 45% (14 out of 31, 2 patients lost to follow-up) in the nonoperated group. The comparison of the two graphs showing pregnancy incidence clearly demonstrates that pregnancies in the nonoperated group occur earlier than in the operated group; it has to be noted, however, that several patients only refrained from being operated on because pregnancy had occurred before surgery was planned. On the one hand, our study confirms other authors' results, i.e. that pregnancy rates in the nonoperated group are relatively high despite present varicocele. On the other hand, the operated group achieved practically the same high pregnancy rate when monitored over a longer period of time.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589928 TI - Treatment of impotence due to venous leakage by resection of the deep dorsal vein of the penis. AB - Ligation and resection of the deep dorsal vein of the penis is a surgical approach to restore potency in venogenic impotence. Between December 1989 and December 1990, we treated 25 men with venogenic impotence by this technique. Additionally, the Nesbit operation was performed in 3 cases due to penile curvature and in 1 case a penile plaque was excised. The patients were asked to come for control 1, 3, 6 and 12 months after surgery. In 14 patients the rigidity and duration of erections were improved 3 months after surgery but, in 21 of the 25 men, erectile dysfunction recurred 6-15 months (average 9.4 months) following surgery and penile prostheses were implanted in 7 cases. The complications were orchiepididymitis in 1 case, penile edema and hyperemia which lasted for 1 week in 1 patient and numbness near the incision site in 10 cases. We conclude that, in patients who had erectile impotence due to venous leakage, resection of the deep dorsal vein of the penis could provide a transient satisfactory result, but should not be considered as a long-term treatment modality. PMID- 1589929 TI - Inhibitory effect of fluoride on renal stone formation in rats. AB - The effect of fluorine (F) on stone formation induced by ethylene glycol (EG) was studied in rats. For different groups, the drinking water was supplemented with EG, sodium fluoride (NaF), EG+NaF, or nothing as control. An isotope-tracing method was used to evaluate experimental stone formation in the kidneys by introducing 45Ca intraperitoneally into rats and then measuring the radioactivity of the kidney. At the end of the 4-week experiment, rats of the EG+NaF group showed a significantly lower incidence of gross urinary stones and lower 45Ca activity in their kidneys compared to the EG group of rats. Both the EG group and EG+NaF group had markedly increased urinary oxalate excretion, with the latter significantly lower than the former (p less than 0.05). Urinary oxalate excretion was relatively lower in the NaF group than in the control group. This study indicates that NaF can inhibit renal stone formation induced by EG by decreasing oxalate synthesis and urinary oxalate excretion, and suggests a possible clinical therapeutic value of NaF in the prevention of oxalate kidney stones. PMID- 1589930 TI - Hypocitraturia as a pathogenic risk factor in the mixed (calcium oxalate/uric acid) renal stones. AB - A small group of patients with nephrolithiasis who forms mixed (calcium oxalate and uric acid) calculi presents particular problems in their clinical management. In 3,158 stones analyzed in our laboratory, we found 158 mixed calculi in 86 of the patients. In this work, the clinical and biochemical results obtained from 27 patients with mixed stones were compared with those from 27 control patients with calcium oxalate renal lithiasis. A significant difference was found in oxalate and citrate urinary elimination (mean +/- SD) in mixed stone formers versus pure calcium oxalate stone formers: oxaluria (mg/24 h: 38 +/- 15 vs. 28 +/- 12; p less than 0.01) and citraturia (mg/24 h: 214 +/- 139 vs. 437 +/- 303; p less than 0.01). Citraturia was decreased in a high proportion (77%) in mixed stone formers, and only a reduced percentage of them (23%) presented normal values, although in the low limit of normality. As treatment and prophylactic measure, we proposed oral administration of citrates in mixed stone patients because citrate inhibits spontaneous nucleation of calcium salts and crystal growth, and it also increases the urinary pH with a consequent increase in uric acid solubility. PMID- 1589931 TI - Infantile multilocular renal cyst. AB - A case of a Japanese 14-month-old male infant with multilocular renal cyst is presented. He was admitted with a chief complaint of an abdominal mass. Although clinically and radiographically multilocular renal cyst in the right kidney was suspected, total nephrectomy was performed because of extreme difficulty of partial nephrectomy and impossibility of complete neglect of malignant cystic tumor. Microscopically, immature glomeruloid tissue, primitive tubules, rhabdomyocytes and nerve fibers were noted. The histological diagnosis of multilocular renal cyst with partially differentiated dysplasia was made. Since the first report by Edmunds in 1892, the etiology of multilocular renal cyst has been discussed for years. In our present case, the pathologic findings suggest that multilocular cystic formation in the right kidney might be the result of developmental disturbances. PMID- 1589932 TI - Three-dimensional imaging of left-sided vena cava: a case report. AB - A case of a left-sided vena cava with primary aldosteronism is presented. Preoperative computerized tomography revealed a left-sided vena cava. We also used a new method, three-dimensional visualization, for diagnosis of the present case. This method provided us with a superior image of the anomalous vena cava. PMID- 1589934 TI - Prostatic abscess drainage: clinical-sonography correlation. AB - Three cases of prostatic abscess are presented, clinically diagnosed, and verified through transrectal sonography. The diagnostic methods and treatment performed are commented on. PMID- 1589933 TI - Primary retroperitoneal tumors. AB - The pathological classification, diagnosis and therapy of primary retroperitoneal tumors are presented. Three typical cases from our clinical experience are described. Ultrasonography is the most important screening method for the early diagnosis of primary retroperitoneal tumors. Early diagnosis and total surgical excision offer the only hope for successful treatment. PMID- 1589935 TI - [State of auditory function based on data of audiometry and dynamic impedance metry in persons exposed to radiation during liquidation of the Chernobyl AES accident]. AB - A total of 251 men at the age of 23 to 50 have been examined with the use of audiometry and dynamic impedance metry who had obtained various doses of radiation connected with the work at the Chernobyl Power Plant. It was established that in 57.8% of the cases the audition was within the physiological norm and in 42.2% various forms of audition derangements were diagnosed. PMID- 1589936 TI - [Malignant external otitis]. PMID- 1589937 TI - [Use of helium-neon laser device LTM-01 in the treatment of patients with chronic suppurative otitis media]. AB - The all-purpose small-sized portable helium-neon laser unit LTM-I has been tested in a clinic. The unit is constructed on the basis of a quantum generator of 0.5 1.0 mW with a wave length of 632.8 nm. The unit is provided with special appliances allowing emission to be brought to the external auditory passage and the tympanic cavity. The unit was used to treat 110 patients with chronic purulent middle otitis. Exposure lasted 10-12 min. The treatment course consisted of 7-12 sessions. The favourable effect was noted by the 6-7th day of treatment in 52 patients with chronic purulent mesotympanitis with a protracted torpid course. Improvement of the cytological picture, disappearance of the microbial flora, normalization of immunological indices made it possible to arrive at a conclusion on the existence of a certain adaptogenic mechanism of action of laser emission. PMID- 1589938 TI - [Use of discrete plasmapheresis in severe forms of laryngeal papillomatosis in children]. PMID- 1589939 TI - [Benign tumors of the laryngopharynx]. AB - Benign tumours of the laryngopharynx are mainly vascular tumours. Thirty two persons with the given pathology were under observation. The main clinical symptoms of the disease are the appearance of blood in the sputum, dysphonia, dyspnea of different degree. The method of choice is radical surgical intervention including tracheotomy, laryngotomy, transverse and lateral pharyngotomy, ligation of the external carotid artery. PMID- 1589940 TI - [Rhinosinusogenic intracranial complications and their diagnosis at present]. AB - Despite the use of strong antibiotics and sulfanilamides the frequency of rhino sinusogenic intracranial complications do not have a tendency to decrease. Rather frequently this is explained by late diagnosis of sinusitis and their intracranial complications. Up-to-date methods of observation help to make both a thorough diagnosis of intracranial rhinosinusogenic complications and simplify the technique of differential diagnosis between brain abscess and meningoencephalitis. PMID- 1589941 TI - [Conservative surgical treatment of laryngeal carcinoid]. PMID- 1589942 TI - [Surgical restoration of the vocal function after laryngectomy]. AB - The restoration of the voice function in patients after total laryngectomy is an important problem, which can be resolved using polymer tracheoesophageal valves. These authors have developed a new tracheoesophageal valve from a biocompatible polymer with an original unilateral lock as well as a procedure of its implantation during laryngectomy. Altogether 9 patients with laryngeal cancer stage III-IV underwent surgery. The high success rate of voice restoration was observed in 6 patients. The procedure is simple in use and will be further modified. PMID- 1589943 TI - [Prevention of diseases of the respiratory tract in sanatoria and preventive establishments]. PMID- 1589944 TI - [Aspergilloma of the maxillary sinus visualized by contrast radiography as a foreign body]. PMID- 1589945 TI - [Foreign body in the nasal cavity]. PMID- 1589946 TI - [Osteoblastoclastoma of the frontal bone in a 10-year-old child]. PMID- 1589947 TI - [Intranasal surgery (selected chapters)]. PMID- 1589948 TI - [Treatment of patients after tonsillectomy]. PMID- 1589949 TI - [Scientific, teaching and medical activities of Professor M. A. Shuster]. PMID- 1589950 TI - [Possibilities of computerized tomography in destructive bone changes in patients with polypous rhinosinusopathy]. AB - The authors made a CT investigation of 15 patients (11 men and 4 women) suffering from polypous rhinosinusopathy. Thirteen patients prior to it underwent polypectomy of the nose. Ophthalmocele was observed in 7 patients. The results of CT investigation made it possible to define the spreading of the destructive process in the accessory nasal sinuses in its polypous lesion and reject a tumor process. PMID- 1589951 TI - [Mechanisms of lesions of nasal mucosa microcirculation in allergic rhinitis]. AB - Morphological study of tissue of the mucous membrane of the nasal cavity in 36 patients which was removed in the process of surgical treatment showed a marked disorder of microcirculation. Immunoluminescent studies revealed fixed globulins and a complement in the vascular wall. PMID- 1589952 TI - Defective in vitro motility of polymorphonuclear leukocytes of homozygote and heterozygote Chediak-Higashi cats. AB - The in vitro migratory responses of neutrophils of homozygote and heterozygote Chediak-Higashi cats were defective in an under-agarose assay when compared to the behavior of phagocytes of control cats. The linear distances traversed by the leading front of migrating Chediak-Higashi neutrophils toward streptococcal culture supernatant, zymosan-activated serum or buffer were reduced and smaller numbers of Chediak-Higashi phagocytes populated the resulting migration areas than did cells of control animals. The relative migration parameters of the Chediak-Higashi phagocytes, however, did not differ from the corresponding parameters of control neutrophils in the presence of streptococcal culture supernatant. Therefore, phagocytes of homozygote and heterozygote Chediak-Higashi cats recognized and responded equally well to the bacterial stimuli as did cells of control animals but traveled shorter distances primarily because of a reduced inherent motility. Similar results were also obtained when the feline phagocytes were attracted by zymosan-activated serum. In addition the relative migration parameters of the neutrophils of homozygote Chediak-Higashi cats were reduced and the normalized spatial distributions of their migrating cells were significantly different in the presence of 100% and 20% zymosan-activated serum when compared to the corresponding migration parameters of carrier and control animals. Defective recognition or responses to the higher concentrations of these host derived attractants complicated, therefore, the already reduced inherent motility of the phagocytes of homozygote Chediak-Higashi cats. PMID- 1589953 TI - Antibody avidity in Yorkshire pigs of high and low immune response groups. AB - Avidity indices of antibody to hen egg-white lysozyme (HEWL) were measured by chaotropic ion (SCN-) elution enzyme-linked immunosorbent assay (ELISA) in pigs grouped as high, control or low for various immune and innate resistance-related traits. The avidity index was the molar concentration of SCN- required to reduce by 50% the ELISA optical density value for a given serum. The index was independent of the amount of antibody. Eight- to ten-week-old Yorkshire pigs were immunized with HEWL and serum antibody measured by ELISA as one of five traits used to assign them to high, low or control response groups. Serum antibody avidity for HEWL was evaluated on Day 14 and Day 30 after primary (Day 0) and secondary (Day 14) immunization. The effects of response group, gender, litter, serum IgG concentration and anti-HEWL antibody on avidity were determined using a linear model. Antibody avidity indices varied amongst individuals. Mean avidity indices for sera collected on Days 14 and 30 were 0.61 +/- 0.43 and 1.22 +/- 0.56, with maximum indices of 2.64 and 2.86 respectively. Avidity of secondary response antibody was significantly higher (P less than or equal to 0.05). Pigs of the high response group had significantly higher secondary antibody avidity than those of the control (P less than or equal to 0.08) and low groups (P less than or equal to 0.01). Avidity index was positively correlated with antibody to HEWL on Days 14 and 30 but not to preimmunization serum IgG concentration or to other measured traits. PMID- 1589954 TI - Generation and characterisation of murine monoclonal antibodies specific for cervine immunoglobulin light chain, IgM and IgG. AB - Monoclonal antibodies (mAb) which react with cervine immunoglobulin (Ig) light chain, IgM and IgG were produced using conventional cell fusion technology. Hybridoma supernatants were initially screened for specificity against cervine Ig using an enzyme-linked immunosorbent assay (ELISA). The specificity of supernatants against size-fractionated cervine Ig was further determined. Supernatants were characterised using western blotting and autoradiographic techniques. The mAb OU1G, OU2G and OU3G were specific for cervine gamma-chain of IgG, whereas OU1L was specific for light chain of Ig. A further mAb (OU1M) bound IgM and not IgG. These mAb were found to have varying cross-reactivity against Ig from other species. PMID- 1589955 TI - The effect of adjuvants on active and passive immunity in pregnant deer and their offspring. AB - Experiments were carried out to determine the effects of a range of adjuvants on immunoglobulin M (IgM) and immunoglobulin G (IgG) serum concentrations to a protein antigen administered subcutaneously to farmed female deer following mating. The antibody responses of animals immunised with keyhole limpet hemocyanin (KLH) in Freund's Incomplete Adjuvant (FIA), diethylaminoethyl dextran (DEAE-dextran) and aluminium hydroxide (alum) were compared with the response to antigen administered in the absence of adjuvants. Animals were subsequently challenged with a subcutaneous immunisation of the antigen in saline. Following parturition, the concentration of passively transferred antigen-specific antibody was measured in the serum of the offspring. The polyionic adjuvant, DEAE-dextran, produced the greatest enhancement of both primary and secondary IgG responses to KLH. Offspring suckling from mothers immunised with antigen in DEAE-dextran consequently had higher concentrations of specific antibodies in their serum than other fawns in the experiment. The adjuvants FIA and alum were approximately 20 fold less effective in enhancing antigen-specific IgG than DEAE-dextran but induced greater amounts of antigen-specific IgM. From the results presented in this paper, there is evidence that immunisation of deer during pregnancy may be an effective way of reducing morbidity in both mothers and offspring. PMID- 1589956 TI - Lymphocyte populations in the synovial membranes of dogs with rheumatoid arthritis. AB - Lymphocyte populations in the synovial membranes of dogs with canine rheumatoid arthritis (CRA) were investigated by immunohistochemical staining techniques. T lymphocytes were the predominant cell type distributed throughout the supporting layer of the synovial membranes. B-lymphocytes expressing IgG were seen far more commonly than those expressing either IgA or IgM. Synovial membrane biopsies from normal and osteoarthritic joints did not have the marked cellular infiltrates seen in joints with CRA. The synovial immunohistopathological features in dogs with CRA are similar to those seen in human rheumatoid arthritis. PMID- 1589957 TI - Lysostaphin: immunogenicity of locally administered recombinant protein used in mastitis therapy. AB - A recombinant bactericidal protein, recombinant lysostaphin (r-lysostaphin), that may be useful as an intramammary therapeutic for Staphylococcus aureus mastitis in dairy cattle, was evaluated for immunogenicity to various hosts. Although immunogenicity could be demonstrated in a variety of other species when administered parenterally, oral administration failed to elicit a significant immunological response. Similarly, intramammary infusion of r-lysostaphin failed to elicit significant serum titers in the bovine until 18-21 infusions were administered (total administered dose of 2-3 g of protein). Antibody titers from dairy cattle which did develop an immune response were predominantly of the IgG1 subclass. Dairy cattle with significant anti-lysostaphin titers showed no deleterious symptoms (anaphylaxis, etc.) upon subsequent infusion, and these titers did not effect the in vitro bacteriostatic activity of r-lysostaphin. Intramammary infusion of r-lysostaphin does not elicit any observable effects on the host animal or on the potential efficacy of the recombinant molecule. Intramammary recombinant proteins may be suitable effective and safe infusion products that provide an alternative to classical antibiotic therapy. PMID- 1589958 TI - Potential of a recombinant antigen as a prophylactic vaccine for day-old broiler chickens against Eimeria acervulina and Eimeria tenella infections. AB - A genetically engineered Eimeria tenella antigen (GX3262), produced as a fusion protein with beta-galactosidase and identified with a monoclonal antibody, induced partial but significant protection in young broiler chickens against experimental E. tenella and Eimeria acervulina infections. The antigen appears to share a T-helper cell epitope with the parasite as evidenced by (a) booster inoculation with either the recombinant antigen or with a small number of live oocysts enhanced the protective immunity in GX3262 primed chickens, and (b) ability of the antigen to induce in vitro stimulation of T-cells from chickens immunized with antigen or parasite. These observations suggest the feasibility of a single vaccination of 1 or 2-day-old broilers with GX3262 to induce an acceptable degree of protective immunity. The implications of the observations reported here are far reaching in terms of a practical coccidiosis vaccine for poultry, and show for the first time that 1-day-old broiler chickens can be efficiently vaccinated with a recombinant antigen against one or more species of Eimeria. PMID- 1589959 TI - The influence of immobilization stress on natural killer cytotoxic activity in halothane susceptible and resistant pigs. AB - In halothane-susceptible (Hal+) and halothane-resistant (Hal-) Belgian Landrace pigs, the influence of immobilization stress on cytotoxic activity of natural killer (NK) cells was evaluated. Four hour immobilization causes biphasic changes in cytotoxicity, i.e. an initial increase followed by a subsequent depression. In both groups of pigs stress-induced suppression of NK cell activity lasted for several days in the post stress period. Throughout the experiment, i.e. before, during and after stress, the level of cytotoxicity was higher in Hal+ than in Hal pigs. PMID- 1589960 TI - Extravasation of lymphocytes via paracortical venules in sheep lymph nodes: visualization using an intracellular fluorescent label. PMID- 1589961 TI - Development of a supersensitive polymerase chain reaction method for human T lymphotropic virus type II (HTLV-II) and detection of HTLV-II proviral DNA from blood donors in Japan. AB - A supersensitive polymerase chain reaction procedure was developed to detect human T-lymphotropic virus type II (HTLV-II) proviral genome. Six primer pairs covering the various regions of HTLV-II were compared and selected on the basis of specificity and sensitivity. Among them, one primer pair of the pol region of HTLV-II (II pol) was able to amplify and detect even 0.1 fg of the cloned plasmid HTLV-II DNA (seven copies) by regular ethidium bromide staining on polyacrylamide gel. By using this procedure, we screened 189 HTLV-I seropositive blood donors from Yamaguchi and Fukuoka Red Cross Blood Centers, Japan. There were four positive samples detectable with the HTLV-II-specific pol primer pair, as well as with the HTLV-I tax primer pair. The amplified DNAs of two specimens were cloned and sequenced. The sequences of the HTLV-I tax region from both specimens were identical to that of HTLV-I. On the other hand, those of the HTLV-II pol region were identical to that of HTLV-II, except for one base substitution in a clone from one subject. These results indicate that dual infection of HTLV-I and HTLV II in the same persons occurs among Japanese blood donors. PMID- 1589962 TI - Tombusvirus genome may encode the sixth small protein near its 3' terminus. AB - A short open reading frame (ORF), ORF6, potentially encoding a polypeptide (pX) of 32-69 amino acids, was revealed upon computer translation of the 3' terminal regions of tomato bushy stunt, cymbidium ringspot, cucumber necrosis and artichoke mottled crinkle tombusviruses. ORF6 has an initiating AUG codon in a favorable context and is evaluated as expressible, judging the distribution of guanosine residues within the codons. Inspection of the alignment of the four putative products encoded by ORF6 shows statistically significant sequence conservation over 11 SD above the random expectation. Secondary structure predictions based on the Garnier method demonstrate strict conservation of a loop between two beta-strands, thus suggesting functional conservation of pXs. It is suggested that pX is not involved in tombusvirus genome replication and encapsidation in cis. PMID- 1589963 TI - Rapid, sensitive, specific, and quantitative detection of human T-cell leukemia virus type 1 sequence in peripheral blood mononuclear cells by an improved polymerase chain reaction method with nested primers. AB - Improving on the nested double polymerase chain reaction (PCR) described previously, we have developed a new two-step PCR (TS-PCR) method for detecting more specifically the human T-cell leukemia virus type 1 (HTLV-1) proviral sequences in peripheral blood mononuclear cells (PBMC). In our TS-PCR method, the point of modification is to use optimal concentrations of primers in the first amplification step in the range of 0.01-0.025 microM. This increases sensitivity and specificity enough to detect from 1 to 10(5) copies of template DNA without radioisotopes. This method is rapid because of completion in 1 day and is also applicable for quantitative detection of clinical specimens. The data show that the quantitative detection of HTLV-1 proviral sequences by this method correlates with the anti-HTLV-1 antibody titers from serologic analysis of seropositive healthy carriers. Moreover, the TS-PCR method using each specific primer was also attempted for successful detection of other viral genomes; therefore, the principle of this method is widely suitable for routine detection of genomes in the basic and clinical microbiological fields. PMID- 1589964 TI - Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site. AB - Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region. PMID- 1589965 TI - Amino-acid sequence comparison of nepovirus coat proteins. AB - The amino acid sequence of the coat proteins of several nepoviruses was determined by a combination of peptide and nucleic acid sequencing (grapevine fanleaf virus, arabis mosaic virus, tomato blackring virus, grapevine chrome mosaic virus). These sequences were compared and showed homologies ranging from 10% to 69%, and 96.7% for the two arabis mosaic virus strains. 10% homology does not reflect any relationship between viruses, and our results implicate, that nepoviruses, considering the homology of the coat protein sequences of viruses as a parameter for virus taxonomy, may be divided into several subgroups. PMID- 1589966 TI - Report on the Federation of European Biochemical Societies Course on the Plant Virus Genome: Structure and Function. Held at the Latvian Academy of Sciences, Riga, Latvia from April 30, 1991 to May 5, 1991. PMID- 1589967 TI - Road trauma prevention: perspectives. AB - Road trauma is a major public health problem in all motorized societies. Doctors who treat casualties must commit themselves not only to providing optimum care but to becoming equally involved in the epidemiological and sociological aspects of road trauma prevention. The prevention of trauma requires a threefold approach: prevent the crash, prevent injury in the crash, and prevent injury aggravation after the crash. Strategies and program options to implement them have been formulated to reduce traffic injury. These strategies are exposure control, crash prevention, injury control, behavior modification, and post-crash trauma management. The combined experience of war injuries and road trauma has lead to major advances in investigation technology and management procedures and far less costly efforts directed at road trauma prevention. The balance between prevention on the one hand and investigation and procedure on the other needs to be addressed. Productive research adequately funded is essential if prevention initiatives are to succeed in reducing the incidence of highway death and injury. PMID- 1589968 TI - Traffic safety education: panacea, prophylactic or placebo? AB - Education is one of the strategies available to reduce traffic crashes and the resultant personal injury. It is seen by many as the major strategy for achieving lasting change. However, there is considerable debate as to the effectiveness of traffic safety education programs to date and, in an era when public expenditure is strongly influenced by the results of cost-benefit analyses, the more fundamental traffic safety education programs are under increasing challenge. The literature on effectiveness is indeed confusing. All too often, programs have commenced from a position of blind faith and have been implemented unsystematically, without specific objectives, targets, or evaluative milestones. The problem is compounded by the considerable methodological difficulties which confront the evaluators of long-term programs of behavior change. If traffic safety education is to survive as a viable countermeasure, program planning and execution must become far more scientific and evaluation must become an integral component. There is also an arguable case for the funds for the longer-term behavior change programs to come from the more general public health arena than from the narrower traffic safety field, while the short-term, specific educational programs should compete directly for funds with alternative traffic safety measures available for the given problem. PMID- 1589969 TI - Helmet efficacy in the prevention of bicyclist head injuries: Royal Australasian College of Surgeons initiatives in the introduction of compulsory safety helmet wearing in Victoria, Australia. AB - The results of a comparative study of the injury profiles of Victorian motorcyclist and bicyclist casualties were used by the Royal Australasian College of Surgeons in initiating a state-wide campaign to promote the wearing of approved safety helmets by Victorian bicyclists and to obtain the necessary legislation whereby such wearing would become compulsory. Bicyclist casualties had sustained more frequent and severe head injuries than motorcyclist casualties although the latter had sustained overall more severe body injuries. Increases in voluntary helmet wearing rates and reductions in costs preceded the introduction in July, 1990 in Victoria of compulsory safety helmet wearing by bicyclists. Sixty-four helmets obtained during a study of more than 1,700 Victorian bicyclists wearing and not wearing helmets were evaluated for performance by impact severity testing and findings related to head injury occurrence. Sixteen helmets sustained more than one impact during the accident. All casualties who sustained a severe head injury (Abbreviated Injury Scale greater than or equal to 4) were involved in a collision with a motor vehicle and subjected to more than one impact to the head/helmet and/or the helmet had come off during the accident. Most impacts occurred below the current test lines of Australian and United States standards. Ten percent of impacts were more severe than required in performance standards. Recommendations are made for improvements in the current standard. PMID- 1589970 TI - Reducing traffic injury: size of the problem and lack of research resources. AB - Worldwide, traffic deaths are 500,000 per year and growing. Four nations, China, India, Russia, and the United States of America, have reached levels of 45,000 50,000 traffic deaths per year, although the nature of the problem is quite different in fully motorized countries from what it is in motorizing countries. In motorizing countries the death rates per 10,000 motor vehicles are much higher than in motorized countries, and also the traffic stream is much more varied. Research for the reduction of traffic injuries is funded at a proportionately much lower level than that for heart disease, cancer, or AIDS. Part of the reason for this is the failure of governments to view and to treat the problem of traffic injuries as a public health problem, but rather to view it solely as a transport problem or as a police matter. A case is made for global mechanisms for the transfer of traffic injury reducing technology from fully motorized nations to motorizing nations. PMID- 1589971 TI - Mandatory bicycle helmet use: experience in Victoria, Australia. AB - On July 1, 1990, the legislation requiring wearing of an approved bicycle (safety) helmet by all pedal cyclists, unless exempted, came into effect in Victoria, Australia. The paper describes the more important activities which paved the way for this initiative and presents some preliminary information about the effect of the legislation on wearing rates and head injuries. Since 1980 there has been promotion of helmet use through bicycle education in schools, mass media publicity, support by professional organizations and community groups, bulk purchase schemes, and government rebates for helmet purchases. The Australian Standard for bicycle safety helmets has also been changed to meet community demands for lighter helmets with more provision for ventilation. There has been a steady increase in voluntary helmet use in Melbourne from 1983 to March 1990, as follows: 5% to 70% in primary school children; 2% to 20% in secondary students; and 27% to 40% in adults. In the period after the legislation, with relatively little enforcement, these three groups have shown substantial increases in helmet use rates, rising to 70-90% in most cases. Preliminary data show that the numbers of bicyclists with a head injury have dropped in the period since the legislation came into effect. The possible contributions to this reduction, of less bicycle use and lower risk of head injury in an accident, are discussed. PMID- 1589972 TI - Improving head protection for cyclists, motorcyclists, and car occupants. AB - It appears from this review of the literature that both linear and angular accelerations are important in the production of injury to the brain. These mechanical inputs to the head result in differential movements or strains in the contents of the head. These strains, if large enough, produce the irreversible loss of function or physical disruptions of neural or other tissue, observed following head impacts. Owing to the difficulties in measuring these strains, criteria for injury levels are written in terms of external movements of the head, and for the more easily measurable linear acceleration rather than angular acceleration. Helmets for motorcyclists provide adequate protection for impacts up to about 8 m/s. Their performance could be improved for front and side impacts to the head, and by matching liner and skull characteristics. Bicycle helmets have both hard and soft shell models with similar impact attenuation properties. The compulsory wearing of these helmets in Victoria appears to have reduced the number of head injuries sustained. For car occupants, only in the U.S.A. is there a measure of the degree of head protection, in that the Head Injury Criterion is used for 50 km/h frontal impacts. Car occupants appear to be susceptible to severe head injury in side impacts. Considerable improvements could be made by providing impact attenuation in the head contact areas on the door, roof and B pillar. The seat belt provides protection in frontal impacts, which could be improved further with the addition of an air bag, or by wearing a helmet. PMID- 1589973 TI - Head injuries in infants and children: measures to reduce mortality and morbidity in road accidents. AB - In the 6-year period from 1983 to 1988, 12 infants (less than 24 months of age) and 103 children (2 to 14 years of age) were killed in road crashes in South Australia. This represents an annual incidence of 6.4 deaths per 100,000 children at risk. At least 4 other children were killed in off-road vehicle-related accidents. Of these deaths, approximately half were car passengers, one third pedestrians, and one sixth pedal cyclists. Most of these infants and children died at the accident site or soon after, but 26 of them survived long enough to be admitted to hospitals with neurosurgical units and an audit of these patients suggests that there were at least 3 preventable deaths. However, autopsies of 78 patients show that the great majority of these deaths resulted from devastating brain and/or trunk visceral injuries. Better emergency care and the use of neurosurgical retrieval teams may save some lives. But more lives might be saved by the use of appropriate restraints for infants and children in cars, by reducing the exposure of child pedestrians and cyclists to road traffic, and by mandatory use of helmets by child cyclists. Off-road vehicular accidents are not as a rule included in road crash statistics; the practice of giving small motorcycles to young children has created a new category of vehicular accidents sometimes causing severe head injury. PMID- 1589974 TI - Causes and control of spinal cord injury in automotive crashes. AB - This paper provides a history of automotive safety and a review of biomedical research on human tolerance and occupant protection. It discusses current understanding of body kinematics and impact biomechanics that result in neck injury. Perspective is given on the linkage between mechanical forces that are the cause and physiologic disruptions that are the consequence of spinal cord injury. The public health aspects of injury and disability are discussed as well as the need for injury prevention. PMID- 1589975 TI - Mechanisms of injury and biomechanics: vehicle design and crash performance. AB - This paper reviews briefly the early evolution of the subject of the biomechanics of impacts. Some examples of rule-making of vehicle crash performance are cited to illustrate the need for evaluation of all design changes and regulations in the real world of crashes and injuries. Some background data on the relative frequencies of casualties and types of collisions are given to establish overall priorities. Mechanisms of injuries in frontal collisions for unrestrained and restrained occupants are described to illustrate the relationships between interior localized contacts and injuries to the lower limbs, the chest, and the head. Kinematics of occupants in angled, lateral, and rear collisions are reviewed together with the related injury mechanisms, and rollover crashes with and without seat belt use are mentioned. Motorcyclist and pedestrian kinematics and some of the desirable characteristics of the vehicle exterior are described together with the unfortunate consequences of the current bumper standards. In summary the paper aims to be a general review of crash kinematics and general mechanisms of injury. PMID- 1589976 TI - World progress in surgery--management of adenocarcinoma of the low rectum. PMID- 1589977 TI - Pre-operative evaluation of patients with low rectal carcinoma. AB - Advances in surgical technique and adjuvant therapy have broadened the spectrum of treatment available for patients with low rectal cancer. Combination of careful pre-operative clinical examination with newer, more sophisticated techniques, particularly in the field of imaging, can stage the extent of disease more accurately then previously. Adoption of an extended pre-operative evaluation allows a more rational approach to treatment in the individual, and standardizes criteria for entry into, and interpretation of, future clinical trials. PMID- 1589978 TI - Technique of per anal excision for carcinoma of the low rectum. AB - Per anal excision is suitable for rectal carcinoma that is less than 3 cm and has not invaded into the muscular layer of the rectum. The upper margin of the lesion should not be greater than 7 cm from the anal verge. The entire lesion is excised in its full thickness with a 1.5 cm to 2 cm normal margin, using electrocautery. It is important that the specimen is carefully examined by the pathologist for completeness of the excision and grade of the carcinoma. Abdominoperineal resection should be considered in good risk patients if adequate margins cannot be achieved and if the carcinoma is a high pathologic grade. PMID- 1589979 TI - Endocavitary irradiation in the conservative treatment of adenocarcinoma of the low rectum. AB - Early T1 and small T2 low rectal cancers may be controlled by endocavitary irradiation using the 50 kV Philips machine. The ambulatory treatment performed in the out-patient department consists of 4 applications within 6 weeks. Iridium 192 implant performed under local anesthesia is useful in many cases to give a booster dose to the tumor bed. In a series of 312 patients followed for greater than 5 years, the rates of local and nodal failure were 4.5% and 3.8%, respectively. The rate of death from cancer was 7.7%. After local excision endocavitary irradiation may be used as adjuvant therapy but it is safer to combine external beam and endocavitary irradiation. In the particular case of very poor risk patients with T2 or T3 tumors of the lower third of the rectum, a short course of external beam irradiation (30 Gy within 12 days) followed 2 months later by endocavitary irradiation may be a reliable procedure to prevent permanent colostomy in cases selected according to the patient's condition and the features of the residual disease. Of 67 patients followed for greater than 5 years, 3 patients died of distant metastasis and 5 patients died of local failures. These data, based on close collaboration with surgeons, suggest a reappraisal of the role of radiation therapy in the conservative management of rectal cancer. PMID- 1589980 TI - Electrocoagulation for adenocarcinoma of the low rectum. AB - Cancers of the distal rectum (less than 7.5 cm from the anal verge) that are freely mobile, moderately well or well differentiated, less than 4 cm in size, limited to the bowel wall, and without evidence of metastasis should be considered candidates for treatment with electrocoagulation for cure. Tumor cell ploidy and evaluation with intrarectal ultrasound may in the future add additional useful information with regard to patient selection. Electrocoagulation and laser ablation of tumors may also be useful modalities for palliation of patients with metastatic disease or who are not candidates for curative surgery. PMID- 1589981 TI - Adequate distal margin of resection for adenocarcinoma of the rectum. AB - There are two questions in the surgical treatment of rectal cancer: (1) How far below a palpable rectal cancer should a surgeon cut in order to avoid cutting through cancer and, (2) Given that the surgeon has not cut through cancer, could the chance of subsequent recurrent rectal cancer have been reduced if an even greater length of bowel had been removed. For mobile tumors that are not poorly differentiated the answer to the first question is far enough in order to get a right-angled clamp on below the tumor that will not slip; the answer to the second question is no. PMID- 1589982 TI - Lateral margins of resection in adenocarcinoma of the rectum. AB - Wide dissection of adenocarcinoma of the rectum is difficult because of the fixed structure of the anatomic pelvis. The role of lateral margins, excision of the mesorectum, and extended lymphadenectomy have recently received much attention in the literature in dealing surgically with more advanced rectal carcinomas. The basic question to be resolved in the future is whether additional radical surgery is of more benefit than adjuvant chemoradiation therapy in this setting. PMID- 1589983 TI - Excision of the rectum with colonic J pouch-anal anastomosis for adenocarcinoma of the low and mid rectum. AB - The results of rectal excision with colonic pouch-anal anastomosis are reviewed from a series of 162 patients covering 7 years. All patients have been operated upon in the same institution and consecutively. The follow-up is now sufficient to allow an accurate evaluation of the outcome of the patients. The main goal of this study was to provide a detailed report of the functional results. Continence was satisfactory in 96% of the patients, with either a perfect continence or minor troubles that would not have been detectable other than by a rigorous questioning. The mean number of bowel movements was 2 per 24 hours. Fragmentation of the defecation and urgency were absent. Twenty-five per cent of the patients had to elicit the evacuation of the reservoir with a suppository or an enema. Improvement of function yielded by a reservoir over straight colo-anal and low colo-rectal anastomoses are significant and, as suggested by manometric studies, are directly related to the restoration of a reservoir function. PMID- 1589984 TI - Abdominoperineal resection for adenocarcinoma of the low rectum. AB - Current understanding of the routes of spread of rectal cancer along with technical innovations such as the circular stapler have allowed surgeons to treat most rectal cancers with an anterior resection and low anastomosis. Appropriate use of local therapy options has further decreased the need for abdominoperineal resection (APR). Nonetheless, APR remains the procedure of choice for many distal rectal adenocarcinomas. Numerous factors influence the decision to perform an APR and are discussed in detail. Although mortality for APR has been reduced significantly, morbidity remains high. Specific complications commonly seen after APR are discussed. Operative technique is outlined since much of the specific morbidity of APR can be reduced by attention to detail in the conduct of this complex procedure. PMID- 1589985 TI - Surgical management of locally advanced adenocarcinoma of the rectum. AB - Approximately 5% of rectal cancers are locally advanced with adherence to the vagina, uterus, bladder, prostate, or other structures. Sacral involvement is fortunately rare in primary cancers. In about 50% of patients there is histologic confirmation of tumor invasion in the area of adherence. It is important to recognize the nature of these tumors pre-operatively so that the patient can be prepared for an exenterative procedure should this be necessary. When these tumors are removed en bloc, 5-year survival rates of 50% can be obtained with survival depending on the presence or absence of regional metastasis and also the presence or absence of histologic tumor invasion into adjacent structures. PMID- 1589986 TI - Locally recurrent rectal cancer: surgical strategy. AB - Relapses after "curative resection" of rectal cancer may be localized and thus amenable to surgical treatment. The risk of relapse may be higher than previously believed depending on adequacy and length of follow-up, the diagnostic modalities used, and the number of autopsies performed. Technical refinements such as a distal margin greater than 2 cm, radical pelvic lymphadenectomy, and high ligation of the inferior mesenteric artery at the aorta do not appear to diminish the risk of recurrence. A wider lateral margin and a more complete excision of the mesorectum may be beneficial, but this is yet unproven. Surgery for isolated, locally recurrent lesions should be limited to carefully selected patients and performed in tertiary centers using a team approach. Whether such radical "salvage" procedures are justifiable merits further careful evaluation. PMID- 1589987 TI - The role of intra-operative irradiation in locally advanced primary and recurrent rectal adenocarcinoma. AB - Useful palliation can often be achieved when standard treatment approaches of external beam irradiation and chemotherapy with or without resection are used for locally advanced primary rectal malignancies. Local control and long-term survival are achieved in only 10% to 50% of patients, however, due to the limited irradiation tolerance of surrounding organs and tissues. Encouraging trends exist in separate intra-operative irradiation analyses from Massachusetts General Hospital and Mayo Clinic with regard to improvement in local control and possibly survival of locally advanced rectal lesions, warranting continued evaluation of such approaches. Disease control within the intra-operative and external irradiation field is decreased, however, when the surgeon is unable to accomplish gross total resection. Therefore it seems reasonable to consistently add 5 Fluorouracil with or without Leucovorin during external irradiation and to evaluate the use of dose modifiers, such as sensitizers or hyperthermia, in conjunction with intra-operative irradiation. Since high systemic failure rates exist with both locally advanced primary and recurrent lesions, more effective chemotherapy needs to be evaluated during external irradiation as well as after completion of such. In view of survival advantages with 5-Fluorouracil plus Leucovorin versus 5-Fluorouracil alone for metastatic disease, this regimen is currently being employed. Even with locally recurrent lesions, the aggressive multimodality approaches including intra-operative irradiation have resulted in improved local control, and long-term survival rates of 20% to 25% versus an expected 5% with conventional techniques in historical series. PMID- 1589988 TI - Role of pre-operative irradiation for anal preservation in cancer of the low rectum. AB - Since 1979, 157 patients with T2, T3, or T4 cancer of the lower rectum have been treated by a short course of irradiation, 30 Gy within 12 days by cobalt 60 using 120 degrees arc rotation on a sacral field, followed by a 2-month rest before surgery. The operative specimens were tumor-free in 13% of patients, Dukes' A in 40% of patients, Dukes' B in 22% of patients, and Dukes' C in 25% of patients. Three (1.9%) patients died postoperatively. At 3 years (107 patients) and 5 years (74 patients) the rates of death of local failure were 7.5% and 9.5%, respectively. The 3-year and 5-year disease-free survival were 71% and 58%. Since 1983, the surgeons took advantage of the tumor regression to carry out sphincter saving operation in 67 patients with T2, T3, and T4 tumors of the lower third of the rectum. The proportion of patients treated by restorative surgery instead of abdominoperineal resection has grown significantly during the past 4 years, from 22% to 71%. Diverting colostomy was performed in 10 patients. Anastomotic leakages were observed in 7 patients. Of 31 patients who underwent low anterior resection and were followed 3 to 7 years (mean 4.5 years), 5 patients died of distant metastasis and 3 patients are alive after segmental hepatectomy. One patient had local recurrence which was controlled by abdominoperineal resection. The rate of 3-year disease-free survival was 77%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1589989 TI - Adjuvant therapy for adenocarcinoma of the rectum. AB - Surgical resection continues to be the primary curative modality for patients with adenocarcinoma of the rectum. However, local tumor recurrence in the pelvis and/or distant metastasis may occur in spite of complete excision of grossly visible malignant disease. Surgical and pathologic staging can identify a subset of surgically treated rectal cancer patients at high risk for tumor relapse and death. Irradiation and chemotherapy have been used as adjuvant therapy in conjunction with surgery as single modalities and in combination for patients with high risk rectal cancer. Evidence from controlled clinical trials indicates a significant decrease in local tumor recurrence, and a significant improvement in disease-free and overall survival with the use of combined postoperative irradiation and chemotherapy in this setting. A current national clinical trial in the United States of America is studying whether irradiation can be combined with new chemotherapy regimens which have shown significant therapeutic benefit as surgical adjuvant therapy for patients with high risk colon cancer (5FU + levamisole) and for patients with metastatic colorectal cancer (5FU + leucovorin) to further improve the efficacy of surgical adjuvant therapy for adenocarcinoma of the rectum. PMID- 1589990 TI - Giant cavernous hemangiomas: diagnosis and surgical strategies. AB - From January, 1972 to June, 1989, 51 patients with liver hemangiomas (32 females and 19 males, mean age 35 years) were evaluated for surgical treatment. Diameters of the masses were 5 cm to 20 cm (median 8.5 cm). Nine of the patients had already been treated for cancer. Twenty-two (43.1%) of the 51 patients were symptomatic and 29 (56.9%) patients were asymptomatic. In 34 patients (66.7%) a definite diagnosis of hemangioma was made by scintiscan and/or ultrasound and/or computed tomography and/or angiography while in the remaining 17 (33.3%) patients the diagnosis was uncertain. The most common indications for resection were the presence of a symptomatic angioma, a symptomatic mass with an uncertain diagnosis, and/or lack of a definite pre-operative diagnosis. Surgery was performed on 25 patients. Ten anatomic and 15 atypical resections or enucleations were performed. There were no postoperative deaths. Two further patients, operated for probable hemangioma, were found to have primary hepatic malignancies. In the 26 unresected patients, no complications were observed during follow-up. In 3 patients, hemangioma enlargement was detected by ultrasound, but there were no symptoms. As cavernous liver hemangiomas are now more reliably diagnosed and their natural history is usually uneventful, surgery can be avoided in most cases. However, when a non-resection policy is adopted, an exact diagnosis is essential in order to rule out primary or metastatic cancer. Surgical exploration and treatment should be limited to symptomatic or complicated cases as well as to patients with an uncertain diagnosis. PMID- 1589991 TI - Improved stabilization of conventional (Brooke) ileostomies with the stapler technique. AB - The rate of functional complications of conventional (Brooke) ileostomy is high and endangers the complete postoperative rehabilitation of the patients. About half of these complications (retraction with/without stenosis, intermittent recession, and prolapse) occur within the classical prominent stoma and are caused by displacement of the serosa surfaces. We have stabilized conventional ileostomies in 39 patients with rows of staples placed paramesenterially and longitudinally. The ileum was everted in the classical way in the primary construction of ileostomies in 19 patients. On the other hand, in 11 patients the prominence of the stoma was established by pulling the ileum out through the previously plane-sutured stoma. In addition, 9 patients with ileostomies which were not primarily stabilized were corrected with the stapler technique to treat complications. With follow-up ranging from 0.2 years to 4.2 years, there have been no complications due to sliding of the nipple in these 39 patients. In contrast, there were complications in 37% of 38 patients with non-stabilized ileostomies with follow-up to the second postoperative year. It was more easily reproducible, more exact, and less traumatic to create the stoma prominence by pulling the intestine out from a primarily plane stoma than with classical eversion. With use of the stapler in repairing complications, local ileostomy constructions were no longer required in every second patient. Consequently, a Brooke ileostomy can be constructed more easily with the stapler technique, ensuring long-term function or restoration of function. PMID- 1589992 TI - Early postoperative mortality following cholecystectomy in the entire female population of Denmark, 1977-1981. AB - This paper assesses the risk of dying within 30 days of admission among 13,854 women who had a cholecystectomy performed as the principal operation from 1977 to 1981. The overall crude mortality rate was 1.2%. Women who had a simple elective cholecystectomy performed had a mortality rate similar to women who had a simple hysterectomy. The mortality was significantly higher than in the general female population (p less than 0.05). Increased age, acute admission, admissions to hospital within 3 months prior to the index admission, the number of discharge diagnoses, and the geographical region were significantly associated with increased mortality. Exploration of the common bile duct was associated with higher mortality in the bivariate analysis, but the association disappeared when the number of discharge diagnoses was taken into account. Type of hospital and the population based cholecystectomy rate of the patient's residential area was not associated with mortality. As regards early mortality, it is concluded that simple elective cholecystectomy is a safe procedure before the age of 50 to 60 years. Acute admissions and more than one diagnosis at discharge were associated with an increased mortality, whereas exploration of the common bile duct may not be as important an independent factor as previously assumed. PMID- 1589993 TI - Factors affecting morbidity and mortality in biliary tract surgery. AB - Thirty-six clinical and laboratory parameters in 770 consecutive patients undergoing biliary tract surgery over a 3 year period were analyzed in an effort to define the patients at greatest risk. Twelve parameters had a significant correlation with hospital mortality, while multivariate analysis revealed that septic shock, malignant obstruction, serum albumin less than 3.0 gm%, history of hypertension, and plasma urea nitrogen greater than 20 mg% had an independent significance in predicting postoperative mortality. The presence of more than 2 of these risk factors identified a group of patients with an 18% mortality rate. It is for this group of patients that adequate pre-operative preparation such as fluid resuscitation, prophylactic antibiotics, and nutritional support are essential. The controversial preoperative biliary drainage might be only indicated in this group of patients. PMID- 1589994 TI - Balloon dilatation for anastomotic stricture after upper gastro-intestinal surgery. AB - We report our study on the correlation between the types of anastomosis and the incidence of anastomotic stricture formation in the upper gastro-intestinal tract. Our experience with balloon dilatation is also reported. We examined the incidence of stricture formation among patients who had an anastomosis between the esophagus and stomach following subtotal esophagectomy for esophageal cancer, and esophagojejunostomy following proximal or total gastrectomy for gastric cancer in the past 17 years. Among 283 patients undergoing esophagojejunostomy, 7 cases of stricture (excluding 3 cases of cancer recurrence) were observed (conventional anastomosis 1.8%; stapling anastomosis 4.6%). There were 17 cases of stricture among 56 patients who had anastomosis between the esophagus and stomach following subtotal esophagectomy (conventional anastomosis 28.6%; stapling anastomosis 50.0%). One month or more after the operation, the diameter of the esophagojejunostomy was estimated using a barium study. The mean diameter of the anastomosis using the stapling method was 11.9 +/- 2.9 mm, whereas the mean diameter of serosubmucosal single layer hand-sewn anastomosis (Jourdan's) was 19.8 +/- 2.2 mm, and that of vertical mattress hand-sewn anastomosis was 19.0 +/- 2.0 mm. Balloon dilatation was used in 29 patients with anastomotic stricture of the upper gastro-intestinal tract (esophageal cancer, 19 patients, gastric cancer, 10 patients). With repeated dilatation, we were able to obtain satisfactory efficacy for benign strictures and there were no severe complications. We believe that balloon dilatation is an easy, safe and effective therapy for anastomotic stricture of the upper gastro-intestinal tract. PMID- 1589995 TI - Accuracy of intraoperative ultrasonography in diagnosing liver metastasis from colorectal cancer: evaluation with postoperative follow-up results. PMID- 1589996 TI - Overview of international food composition data bases. PMID- 1589997 TI - NORFOODS computer group. Food composition data interchange among the Nordic countries: a report. PMID- 1589998 TI - Past and present activities in food composition tables in Latin America and the Caribbean Islands. PMID- 1589999 TI - Food composition tables and food composition analysis in east Europe. PMID- 1590000 TI - International food data base: conceptual design. PMID- 1590001 TI - Principles for the preparation of nutritional data bases and food composition tables. PMID- 1590002 TI - Validated data banks on food composition: concepts for modeling information. PMID- 1590003 TI - LanguaL. An automated method for describing, capturing and retrieving data about food. PMID- 1590004 TI - [Pathogen modulating and immunomodulating aspects of antibiotic therapy]. PMID- 1590005 TI - [Immunomodulating effects of antibiotics alone and in conjunction with immunosuppressive drugs]. PMID- 1590006 TI - [Lincosamine as indirect biological response modifier]. PMID- 1590007 TI - [Physiologic microflora, antibacterial therapy and their effect on the immune system]. PMID- 1590008 TI - [Long-term therapy of peptic ulcer]. PMID- 1590009 TI - [Historical overview of the development of public health statistics in the first half of the 20th century--1]. PMID- 1590010 TI - [Medical history significance of the last Mozart portrait--a deathly serious impetus for smiling and reflection]. PMID- 1590011 TI - [Anal incontinence in patients with Addison's disease: a gluco- and mineralocorticoid independent sphincter malfunction?]. AB - Anorectal motor function was evaluated in 15 female patients with Addison's disease and androgen deficiency and 15 age-matched healthy volunteers. Medical history revealed symptoms of faecal incontinence in 5 patients. The patients showed decreased maximum retention volumes (p less than 0.01) in the rectal saline infusion test. Lowered anal sphincter resting (p less than 0.01) and squeeze pressure (p less than 0.01) was demonstrated in patients with adrenocortical insufficiency. No differences between patients and controls were found in respect of perception volume, minimal distension volume for sphincter relaxation and rectal compliance by means of intrarectal balloon distension. Electromyography of the external anal sphincter was performed in 8 patients and showed no evidence for a neurogenic defect. Relevant morphological changes of the anorectum could be excluded endoscopically in 13 of the 15 patients. Therefore impaired anorectal muscular function is responsible for faecal incontinence in patients with Addison's disease and androgen deficiency. Further investigations will show, whether these findings are the consequence of lowered androgen production. PMID- 1590012 TI - [Stomach tolerance of various fluoride preparations. An endoscopy controlled single-blind study of healthy probands]. AB - In 12 healthy volunteers the gastro-duodenal damaging effects of Ossiplex retard tid, Mono-Tridin tid and Ossin bid were investigated in a randomised, single blind cross-over study. Prior to the start of the three therapeutic phases subjects underwent endoscopic examination to exclude gastro-duodenal mucosa lesions. On day 14 of therapy 2 hours after the application of the last fluoride dose subjects underwent endoscopy again. The 14 days administration of Ossiplex retard, Mono-Tridin und Ossin led to gastro-duodenal mucosa lesion scores of 0.42 +/- 0.26; 1.50 +/- 0.54 and 2.08 +/- 0.71 (mean +/- SEM) respectively. These differences were statistically significant when comparing Ossiplex retard vs Ossin (p less than 0.05), but not Ossiplex retard vs Mono-Tridin. Regarding the number and the severity of lesions the differences between the gastro-duodenal mucosa damaging potency of the three fluoride preparations were also evident. With Ossiplex retard only in three subjects petechiae (n = 1) and antral erythemas (n = 2) were observed. Under Mono-Tridin and Ossin, however, a higher grade of lesions i.e. erosions and an ulcer were seen endoscopically. This study shows that the slow release fluoride preparation Ossiplex retard demonstrates a lower gastro-duodenal mucosa damaging potency when compared to the other fluorides Ossin and Mono-Tridin. There was no relationship between serum fluoride concentrations and the grade of gastro-duodenal mucosa lesions. PMID- 1590013 TI - Does computed tomography improve patients selection for extracorporeal shock wave lithotripsy (ESWL) of radiolucent gallbladder stones? AB - In 97 patients with radiolucent solitary gallbladder stones, the density of the calculi was evaluated by computed tomography (CT) prior to extracorporeal shock wave lithotripsy (ESWL). Sixty-three percent of the stones were isodense to bile (mean 48 +/- SD 11 HU), and 37% could be identified on CT-sections (maximal density 105 +/- 46 HU, mean density at the largest cross-section 53 +/- 31 HU). There was a slight trend toward better stone fragmentation and higher clearance rate in patients with isodense stones. However, the probability of complete fragment clearance was not significantly different in stones with a high or low CT-density. From these data we conclude that stone selection for ESWL and adjuvant bile acid therapy in patients with radiolucent solitary stones as assessed by oral cholecystography is only marginally improved by computed tomography. PMID- 1590014 TI - [Clinical aspects and surgery of complicated and uncomplicated Meckel's diverticulum]. AB - Our series of 43 complicated and 35 uncomplicated cases of Meckel's diverticula is reviewed. The complicated courses displayed the typical symptoms, e.g. ileus, hemorrhage, inflammation, perforation with peritonitis. Indication and tactics and techniques of surgical intervention are based on the individual course. Incidental diagnosis of Meckel's diverticulum during coeliotomy indicates resection, because diverticula of normal gross appearance present with microscopic alterations in 29% which could evoke major complications. PMID- 1590015 TI - Diagnostic problems in nodular regenerative hyperplasia (nodular transformation) of the liver. Review of the literature and report of two cases. AB - Nodular regenerative hyperplasia (NRH) is a rare lesion of the liver associated with portal hypertension in more than half of patients. We present two cases demonstrating complications and diagnostic problems of NRH and review the pathogenesis, clinical, radiologic, and pathologic features of 240 cases in the literature. Patient 1 died from variceal bleeding as a complication of NRH. Patient 2 presented with ascites. Sonographic, computed-tomographic and magnetic resonance findings did not differ from liver cirrhosis. Three needle biopsies showed nonspecific reactive hepatitis. Wedge liver biopsy provided the correct diagnosis of NRH and a shunt operation was performed. Non-Hodgkin's lymphoma (centroblastic type) was diagnosed three years after NRH. At present there is no clinical or radiologic evidence of progression of NRH in this patient. The diagnosis of NRH cannot be made without histologic examination. Correct diagnosis is difficult in percutaneous needle biopsy. Therefore, laparoscopically guided liver biopsy or wedge biopsy is often necessary for diagnosis. NRH should be included in the differential diagnosis of portal hypertension. Portal diversion can be considered. PMID- 1590016 TI - [Doppler ultrasound detection of ischemic colitis]. AB - A 67 year old female patient came to admission because of colic abdominal pain and suspicion of intestinal bleeding. Coloscopically we found disseminated ulcerations within hemorrhagic swollen mucosa at left flexure, right and lower colon were without pathological finding. We thought of ischemic colitis and performed endoscopic dopplersonography. A reduced flow noise over the anastomotic loop between upper and lower mesenteric artery was evident. By means of histology and radiology ischemic colitis was confirmed and after therapy cicatrical healing resulted. As far as we know for the first time ischemic colitis could be recognized with endoscopic dopplersonography. PMID- 1590017 TI - [Pathogenesis of Wilson's disease]. AB - Wilson disease is due to a genetically determined impairment of copper excretion from liver into bile resulting in copper overload of the organism. The chromosomal defect and the primary defect of copper metabolism is not yet defined. When during the course of the disease the cytoplasmatic copper binding sites of hepatocytes are saturated, excess of "free" copper is accumulating. It induces liver cell damage and necrosis followed by the development of fibrosis and cirrhosis. The accumulation process of excess free copper in hepatocytes is accompanied by a redistribution into the lysosomal compartment of the cells as well as by release of free copper into blood. This increase of the free serum copper concentration leads during the course of the disease to an elevated copper burden of other organs. This results in a variety of symptoms, of which liver disease and neurologic disturbances are of major significance in regard to clinical presentation and prognosis of the patients. PMID- 1590018 TI - [Electronic documentation of findings, performance statistics and image analysis in endoscopy]. AB - Endoscopic data processing in endoscopy departments can hardly be performed without electronic data management nowadays. Written report and endoscopic image storage have to be performed in parallel applying modern sophisticated electronic systems. Sufficient storage capacity has to be taken care for. In the near future image processing of electronically storage endoscopic images will become available. PMID- 1590019 TI - [Alpha 1-antitrypsin as an endogenous marker for the detection of intestinal protein excretion--problems and controversies in dealing with a new method]. PMID- 1590020 TI - [Intracellular activation of pancreatic proenzyme as a physiologic process?]. PMID- 1590021 TI - [Guidelines for endoscopic studies of infectious cholangitis]. PMID- 1590022 TI - [Extending informative value of intracranial pressure measurement by cerebral pressure amplitudes (Pa)--analysis of average intracranial pressure (Pm)]. AB - One aim of the intracranial pressure measurement is observing constantly patients with intracranial space-occupying factors and therefore to act diagnosticly and therapeutically correct at the right time. Through the continual registration of the intracranial pressure amplitude in relation to the medium intracranial pressure it is earlier possible to forecast intracranial pressure rise and to deal with this than with just the simple measurements of medium intracranial pressure. With 40 neurosurgical patients such examinations were undertaken after implantation of a ventricle catheter. The value of this method was proven during the continual observation of the patient. PMID- 1590023 TI - [Improved patient monitoring during intracranial pressure measurement by calculating a theoretical pressure-volume curve]. AB - Patients with an acute "brain damage" where an intracranial pressure rise can be suspected due to the pathophysiological context are an indication for intracranial pressure measurement. For registrating the reduction of the intracranial reserve space before the rise of the medium pressure, volume-loads from the side-ventricles were undertaken with 54 neurosurgical patients. A better bedside monitoring is possible though the mathematical registration of those factors which indicate the size of the functional intracranial reserve space. With the calculated parameters of the reserve space (pressure-volume-index) a theoretical pressure-volume-curve was demonstrated. PMID- 1590024 TI - [The gamma nail. Indications, technique and early results]. AB - It is reported about indication, technique and the first results of 40 osteosynthesis carried out in proximal femur fractures with the help of a gamma nail. The indication of the gamma nail ranges from the lateral fracture of the femoral neck to subtrochanteric fractures of the femur. According to existing experiences the following conclusions could be drawn: The technique of this modern interlocking nailing is to be learned in a short time period. The instruments are practically compiled and in case of a suitable use the handling is free of complications. It could be used in all stable and instable pertrochanteric fractures. The possibility of an immediate postoperative load of the fracture is one of the essential advantages of this method. PMID- 1590025 TI - [Ipsilateral femoral fractures following artificial hip joint replacement. An unavoidable complication]. AB - During a 22 years period 21 of altogether 5,229 patients with artificial hip joint replacement had subsequent ipsilateral femur fracture. The avoidance of this complication, its etiology, forms of fracture and therapeutical management are discussed. PMID- 1590027 TI - [Tibial head opening-wedge osteotomy with homologous spongiosa in comparison with tibial head closing-wedge osteotomy with external fixator]. PMID- 1590026 TI - [The treatment concept and results of peri-/sub-prosthetic fractures]. AB - The treatment of choice in ipsilateral femoral shaft fractures in patients with hip prosthesis depends on the location of the fracture lines and the observation of loosening of the prosthesis. Either a change of prosthesis, if necessary in combination with refixation of the greater trochanter or simple open reduction with internal fixation (ASIF) along with autologous and/or homologus spongiosa are the used techniques. The rate of complications in peri- or subprothetic fractures is high. Lack of motion in hip and knee joint occurs frequently. PMID- 1590028 TI - [Results of treatment of early functional therapy following incomplete fibular ligament rupture]. AB - Up to now, the inversion trauma of the ankle joint is one of the most important and frequent injuries. The functional treatment has come to a point of advantages in the therapeutic regime. Nevertheless a follow-up is necessary. In a follow-up examination, in the average of 27 months after trauma, 90.3% of the patients have satisfactory or better results. In all patients a stress tenography is carried out. Between radiologic finding and clinical situation is no direct correlation. In the treatment of fibular ligament rupture it is necessary to find out the patients with chronic instability. They have a benefit in an early reconstructive operation of the fibular ligaments. PMID- 1590029 TI - [Extra-articular chondroma of the knee joint]. PMID- 1590030 TI - [Clinical importance of the ligamentum epitrochleo-anconaeum]. PMID- 1590031 TI - [Transgenicular amputation with myocutaneous gastrocnemius flap in arterial occlusive disease]. AB - 41 knee disarticulations in patients with gangrene due to periphere vascular disease were performed using a myocutaneous flap of the gastrocnemius muscle as described by Klaes and Eigler in 1985. In many cases disarticulation was preceeded by reconstructive vascular procedures or amputation at a lower level. Primary healing of the stump was achieved in 80% of the cases. 29% of the patients were able to walk with the aid of a prosthesis. PMID- 1590032 TI - [Experimental study of metallic bone and joint prostheses with plasma-sprayed ceramic coating]. AB - In order to solve the loosening problem of endoprosthesis, a titanium-based alloy bone and joint prosthesis with plasma-sprayed ceramic coating was developed by the authors. By the fabrication powdered alumina or zirconium oxide were melted in an electric arc by a temperature of 10,000 K and sprayed onto the metallic prosthesis. The coating was 0.3 to 0.6 mm in thickness and had innumerable micropores. The pores were 50 to 200 microns in diameter. The metallic bone and joint prosthesis with plasma-sprayed ceramic coating exhibits characteristics of metal and ceramic, such as high mechanical strength, high resistance to corrosion and elution and good biocompatibility. According to our experimental study, the plasma-sprayed ceramic coating allows tissue ingrowth into its micropores and prevents the loosening of the prosthesis. Successful cases have been experienced through 10 years clinical application. PMID- 1590033 TI - [The ionized calcium in the blood of domestic chickens: dependence on age and sex]. AB - In the present study concentration of ionized calcium and the correlation between total and ionized calcium in blood of domestic fowl and its dependence on age and sex were investigated. Furthermore a possible influence of blood sampling procedure on the measured values was assessed. Leghorn chickens of either sex, aged 3, 9, 25, and 80 weeks, respectively, were used. Blood sampling was performed by vein-puncture and indwelling catheters, respectively, of both ulnaris vein and artery of animals which had been fasting for 12 hours. Determinations of ionized calcium concentration was carried out by use of an ion selective electrode (ICA1), and of total calcium concentration in plasma using atomic absorption, respectively. After attainment of sexual maturity total calcium in roosters rose from 2.73 to 2.85 mmol/l, whereas ionized calcium fell from 1.45 to 1.40 mmol/l and per cent fraction of ionized/total calcium (extent of ionization) from 53.1 to 49.1%, respectively. After attainment of sexual maturity in hens, the content of total calcium in venous blood rose from 2.78 to 5.78 mmol/l, and of ionized calcium from 1.45 to 1.59 mmol/l, respectively, whereas the extent of ionization was significantly reduced from 52.2 to 27.1%. On comparison of the vein-puncture and indwelling catheter technique a marked influence of the blood sampling procedure on calcium concentrations measured in blood of chicken became evident. On attainment of sexual maturity both the arterial and the venous blood (sampled from indwelling catheters) of hens showed levels of ionized calcium about 8% higher as compared to roosters. The extent of ionization amounted to 39% in sexually mature females as opposed to 51% in males. Concentrations of calcium ions in venous blood averaged 0.07 to 0.08 mmol/l higher compared to arterial blood in either sex. Concentration of ionized calcium did not exhibit any correlation to total calcium in adult animals. However, the concentration of ionized calcium was inversely correlated to blood pH. PMID- 1590034 TI - [The ionized calcium in the blood of domestic chickens: dependence on the laying cycle]. AB - In the present study the plasma concentration of both ionized and total calcium in arterial as well as in venous blood of Leghorn hens and its dependence on the ovulatory cycle were investigated. During the ovulatory cycle, the concentration of ionized calcium in blood of hens follows the course of a sine curve. Maximum calcium ion concentrations (1.58 mmol/l in venous blood and 1.48 mmol/l in arterial blood, respectively) were observed 3 to 6 hours after oviposition, and minimum concentrations (1.26 and 1.19 mmol/l, respectively) at 18 to 21 hours after oviposition. Changes in total and ionized calcium concentration went parallel. Six to 9 hours after oviposition maximum values (4.24 and 4.15 mmol/l respectively) and 21 to 24 hours after oviposition minimum values (3.25 and 2.99 mmol/l, respectively) were measured. The arterio-venous difference was -0.22 mmol/l on average. PMID- 1590035 TI - Villous hypoplasia of the small intestine in neonatal foals. AB - To elucidate the pathomorphogenesis of extremely shortened small-intestinal villi, occurring spontaneously in neonatal foals, the morphology of the small intestine with stunted villi was studied in eight cases. All intestinal wall elements and the villi were poorly developed. Most villi were found to be extremely short throughout the entire length of the small intestine. The villous core consisted of undifferentiated, fibroblast-like cells held loosely together by ground substance which was rich in glycosaminoglycan. Development of the villous lamina propria was poor with respect to capillaries, lymphatic vessels, connective tissues and smooth muscle cells. When compared with the structure of small-intestinal villi in age-matched foals as controls, it appeared that the histological structure of the stunted villous interstitium had remained at the immature state observable during the intrauterine period. Hypoplasia of the intestinal villi was assumed to reduce the functional surface area available for absorption of colostrum, causing malabsorption in newborn foals. PMID- 1590036 TI - [The effect of a different energy supply of growing Great Danes on body weight and skeletal development. 1. Body weight development and energy requirement]. AB - 27 Great Danes (from 3 litters) were fed ad lib. (n = 9) or with an energy intake (n = 18) restricted to 80 and 70% of the paired ad lib. group, respectively, and a nearly equalized protein and nutrient supply meeting the current recommendations (8 dogs of the restricted groups were bearing weight loaded [15% of own BW] belts in the scapular region). Dogs were weighed weekly, shoulder height, approximate length of the forearm and foot were recorded in certain intervals. In plasma protein, urea, Ca, P, Cu, Zn, and alkaline phosphatase were determined. Intake of digestible energy (according to the results of digestive trials) was recorded daily. PMID- 1590037 TI - Hereditary peromelia in Mohair goats. AB - The occurrence of a new congenital defect of the appendicular skeleton in Mohair goats is described. The malformation is peromelia and occurs in a familiar pattern. The defect seems to have an autosomal recessive mode of inheritance with variation in the expressivity of the genotype. The pathological abnormalities were described in 8 cases, all characterized by agenesia of the phalanges and parts of the metacarpus or metatarsus affecting one or more limbs. In some cases additional skeletal defects were found. Furthermore, 5 cases were reported by the owners with a description of the limb affected and 1 case was examined clinically. Predisposition for pelvic limbs to be affected was observed. The defect, which does not seem to have been described in goats previously, is phenotypically similar to and possibly also genetically homologous to a defect described in sheep. PMID- 1590038 TI - Establishment of a pneumococcal septicemia model in the miniature swine. AB - Human pneumococcal septicemia, the prominent postsplenectomy complication, was as yet difficult to study in the porcine model, since this species appeared to be fairly resistant against pneumococcal infections. We have used two strains of pneumococci (serotype 1 and 6B) both of which had been isolated from patients with systemic infection and both of which were maintained in a virulent state by regular mouse passage. After challenge with 10(9) type 1 pneumococci, however, only one of the 5 pigs developed fever, none showed profound hematological alterations and each animal exhibited a rapid clearance of bacteria from peripheral blood. By contrast, challenge of 7 animals with type 6B pneumococci resulted in a slower and incomplete bacterial clearance with persistent bacteremia for up to 24 hours. All animals developed fever and a profound leukopenia with less than 5,000 leukocytes/ml and 3 of the 7 animals died after injection of type 6B pneumococci. The results show that potentially the type 6B pneumococci can be successfully employed for studies of gram positive septicemia in the miniature swine. PMID- 1590039 TI - [The effect of storage time and temperature on the activity of glutathione peroxidase in plasma and whole blood of horses]. AB - The influence of temperature and duration of storage on glutathione peroxidase (GSH-Px) activity in plasma and whole blood samples of horses was investigated. Furthermore the relationships between the GSH-Px activities in plasma and whole blood as well as the GSH-Px values related to hematocrit and the hemoglobin content of the blood samples of 93 different horses were calculated. At 20-22 degrees C, the GSH-Px activity in plasma and whole blood samples remained stable over at least three days while it was reduced by 38% and 65% after 2 and 3 days, if the whole blood samples were kept stored after being diluted (lysate). The GSH Px activity was stable over three days in plasma, whole blood and lysate samples stored at 4 degrees C and -18 degrees C. In lysate samples kept frozen the GSH-Px activity remained stable over a period of 60 days while in plasma samples the activity had fluctuations. The GSH-Px activity in plasma was 12.2 +/- 11.7 nkat/ml, in whole blood 386 +/- 117 nkat/ml. The coefficient of correlation between plasma and whole blood GSH-Px activity was r = 0.27 (p less than 0.01), and between plasma and whole blood related to the hematocrit and to the hemoglobin content of the blood samples 0.38 and 0.35 respectively (both p less than 0.001). Between whole blood and whole blood related to hematocrit and hemoglobin content, r was 0.8 and 0.89 respectively (p less than 0.001). PMID- 1590040 TI - Fine structure of corpora lutea in superovulated heifers. AB - The aim of the present study was to determine the degree of development and structural status of perfusion-fixed day-7 corpora lutea (CL) (using qualitative and quantitative histology at light and electron microscopy levels) in FSH induced superovulated (SO) and untreated heifers. Blood samples were collected daily to monitor the plasma progesterone levels during the FSH treatment up to slaughter 7 days after oestrus. Meanwhile the ovarian activity was followed by ultrasonography and rectal palpation. At slaughter, the ovaries were fixed by vascular perfusion to avoid distortion of the structures and conventionally processed for electron microscopy. The volume density of the luteal tissue was calculated on the examined sections by point-counting. The histology of the corpora lutea, exception made of a higher incidence of degenerated luteal and endothelial cells in the superovulated animals, did not differ from that of the untreated animals, confirming their normal development. The mean weight and volume of the CL in SO animals was 50% smaller than that of the untreated heifers. The progesterone concentration (nmol/l) at day 7 was significantly positively correlated with the number of CLs/heifer (r = 0.93, P less than 0.01), with the weight of Cls/heifer (r = 0.97, P less than 0.005) and with the volume of CLs/heifer (r = 0.97, P less than 0.005). The results indicated that there were no morphological differences, in terms of histological structure and volume density, between the luteal tissue of SO heifers and the luteal tissue of non-SO heifers on day 7 of the oestrous cycle which could interfere with its endocrine function. PMID- 1590041 TI - Changes in osmotic resistance of erythrocytes of cattle, pigs, rats and rabbits during variation in temperature and pH. AB - The osmotic resistance of cattle, pig, rat and rabbit erythrocytes was determined at different temperatures and pH. At constant pH of 7.7, the resistance of erythrocytes of all these species increased as the temperature increased. However, at constant temperature of 29 degrees C, the resistance of the erythrocytes decreased in acidic solution and increased in alkaline solution. PMID- 1590042 TI - Hip arthroplasty revision. PMID- 1590043 TI - Cemented revision hip arthroplasty. A multicenter 5-9-year study of 204 first revisions for loosening. AB - In a prospective study of total hip replacements in Sweden, the epidemiology of all the reoperations has been documented since 1979. From this nationwide register, the results of initial revision arthroplasty for aseptic loosening were evaluated in a well-described patient population, aged 55 to 70 years at the time of revision. Totally, 202 patients (204 hips) were available for clinical and radiographic analysis. The average follow-up time was 7 years. A re-revision or radiographically loose components occurred in 38 percent of the hips. The survival rate, with re-revision as the end point, was 75 percent at 8 years. We concluded that the initial revision on still active patients, using previous cementing techniques, provided poor results with a high risk of mechanical loosening and re-revisions. The results of this study, obtained in a well described patient population, can be contemplated as a baseline that provides an opportunity for valid comparisons of new techniques. PMID- 1590044 TI - Unsatisfactory results after repeated revision of hip arthroplasty. 61 cases followed for 5 (1-10) years. AB - 61 cemented second revision total hip arthroplasties and 18 cemented third revision total hip arthroplasties were studied with emphasis on causes of failure, complications, risk of further revision, and clinical and radiographic results of surviving, not further revised patients. Aseptic loosening was the major reason for both second and third revisions followed by recurrent dislocations. Of 61 second revisions, 21 failed again. Postoperative dislocation was the major complication, encountered in 10/61 after second revisions and in 4/18 third revisions. 10 second revisions were reoperated on without exchange of components, but for causes related to the implant. The clinical and radiographic outcome of surviving, not further revised patients was favorable, but must be seen in the light of the high rate of further revisions. In 33 of 53 second revisions and in 5 of 13 third revisions left for evaluation, the outcome was considered unsatisfactory. We conclude that reoperations for failed arthroplasties should be the prerogative of highly experienced centers. PMID- 1590045 TI - Hydroxyapatite coating modifies implant membrane formation. Controlled micromotion studied in dogs. AB - We studied the influence of controlled micromovements between bone and porous titanium alloy implants with and without hydroxyapatite coating. A dynamically loaded unstable device producing approximately 150-microns axial translation of knee implants during each gait cycle was developed. Stable implants served as controls. Matched stable and unstable implants with either porous titanium (Ti) or hydroxyapatite (HA) coating surrounded by a gap of 0.75 mm were inserted into the weight-bearing regions of the medial femoral condyles in 14 mature dogs. Histologic analysis after 4 weeks showed a fibrous membrane surrounding both types of implants subjected to micromovements, whereas various amounts of bone ingrowth was obtained in the stable implants. The membrane around unstable HA implants was thinner than that around unstable Ti implants. Islands of fibrocartilaginous tissue characterized the membrane around unstable HA implants, whereas fibrous connective tissue surrounded unstable Ti implants. The collagen concentration of the fibrous membranes was higher around unstable HA implants compared with Ti implants. Instability reduced the shear strength of the implants. However, the shear strength of unstable HA implants exceeded that of the Ti implants, both unstable and stable. The greatest shear strength was obtained by stable HA implants, i.e., tenfold greater than that of stable Ti implants. The gap-healing capacity around stable HA implants increased toward the HA surface, and was greater than that around Ti implants. Our study demonstrates that micromovements between bone and implant inhibit bone ingrowth and lead to the development of a fibrous membrane. The superior fixation of unstable HA implants compared with unstable Ti implants may be ascribed to the presence of fibrocartilage, a higher collagen concentration, and radiating orientation of collagen fibers in the membrane. The strongest mechanical anchorage and the greatest amount of bone ingrowth was obtained by stable implants coated with hydroxyapatite. PMID- 1590047 TI - Early physeal closure after femoral chondrodiatasis. Loss of length gain in 5 cases. AB - Chondrodiatasis (symmetric physeal distraction) was carried out in 5 patients with short femora because of congenital dislocations of the hip joint (4 patients) and congenital shortening (1 patient). In all but 1 case the physis closed shortly after lengthening, and loss of gained length or further shortening ensued in all of them. Chondrodiatasis should be avoided in the subjects under 13 years of age with mild leg-length discrepancies. PMID- 1590046 TI - Intermittent micromotion inhibits bone ingrowth. Titanium implants in rabbits. AB - We studied the effects of micromotion on bone ingrowth into a 1-mm canal through a titanium chamber implanted in the proximal tibia of rabbits. The implant surface became "osseointegrated," but an interior core was movable, allowing the central portion of the canal to be moved in relation to the ends. Thus, the ingrowing bone in the canal had to pass an area of ad latus motion. When implanted in rabbit tibiae, the canal became filled with ingrown cancellous bone. Bone ingrowth was inhibited by 20 cycles of 0.5-mm movement applied during a 30 second period once daily. With this regimen, the canal was usually filled with vascularized fibrous tissue and significantly less bone. The micromotion chamber may enable detailed studies of the effects of different motion variables on ingrowth of bone. PMID- 1590048 TI - Increasing incidence of hip fracture in Crete. AB - In Crete, 459 patients with a hip fracture were treated during 1986 and studied prospectively. The female/male and trochanteric/cervical fractures ratios were both 2. The majority of the patients (96 percent) were 50 years of age and over. The incidence was found to be 10 per 10,000 inhabitants for the whole population, whereas in the age group of 50 years and over, it was 30; and in the age group of 80 years and over, 140 per 10,000. From 1982 to 1986, the annual number of patients with a hip fracture increased by 20 percent, while the population 50 years and over remained practically unchanged. Compared with Scandinavia, the number of fractures in Crete is lower, and the proportion of trochanteric fractures is higher. PMID- 1590049 TI - The accuracy of measurements of femoral neck fractures. Conventional radiography versus roentgen stereophotogrammetric analysis. AB - Postoperative displacement of the femoral head center was measured in 60 intracapsular hip fractures at repeated conventional radiographic (CR) and roentgen stereophotogrammetric (RSA) examinations. The measurements of the conventional radiographs (405 pairs) were done on a digitizing table. Totally, 105 pairs of these radiographs (AP and lateral, CR) were measured by 2 observers. Manual measurements were also made on 176 pairs of the conventional radiographs. Conventional radiographs tended to overestimate or underestimate the average displacements up to about 2 mm. Two standard deviations of the differences (RSA CR) varied from 5.8 to 9.6 mm depending on the direction of the movements. The accuracy of the measurements on conventional radiographs did not differ between the 2 examiners. The digitizing table was found to be more accurate than the manual measurements. The accuracy of conventional radiography can most likely be improved by using a strictly standardized examination technique. PMID- 1590050 TI - Incidence of Perthes' disease in Uppsala, Sweden. AB - The annual incidence of Perthes' disease in Uppsala County, Sweden, was computed for the years 1978-1989 and further analyzed as regards age and sex distribution. The annual incidence was 8.5 per 100,000 in children 0-14 years of age. PMID- 1590052 TI - Percutaneous bone-marrow grafting of osteotomies and bony defects in rabbits. AB - The effects of percutaneous bone-marrow grafting done on the fifth day after osteotomies and induced defects of the shaft of the radius were studied in 41 adult rabbits. At 2 and 3 weeks, the callus volume was larger in the grafted radii than in the controls. Serial radiographs and gross and histologic findings confirmed that percutaneous bone-marrow grafting improved healing of osteotomies and defects at 4 weeks. PMID- 1590051 TI - Scintimetry after total knee arthroplasty. Prospective 2-year study of 18 cases of arthrosis and 15 cases of rheumatoid arthritis. AB - 33 consecutive patients (18 arthrosis, 15 rheumatoid arthritis), operated on with total knee arthroplasty and randomized to cemented (18 knees) or cementless fixation (15 knees), were investigated with scintimetry 3, 6, 12, and 24 months postoperatively. Migration was evaluated with simultaneous roentgen stereophotogrammetric (RSA) examinations. The scintimetric activity in the ipsilateral femoral diaphysis decreased and the activity in the tibial diaphysis increased during the observation period. Constant and low activity was recorded in front of the femoral component. This region was chosen as a reference. Three months after surgery, high activity was noted under the tibial component in knees with a preoperative varus deformity. After 2 years, the activity had decreased to the same level as in the patients with a valgus deformity. Diagnosis and mode of fixation did not influence the activity. Low postoperative activity was recorded in the tibial metaphyses if no rotatory displacement of the tibial component occurred. PMID- 1590053 TI - Graft perforations favor osteoinduction. Studies of rabbit cortical grafts sterilized with ethylene oxide. AB - The healing of freeze-dried, ethylene oxide sterilized, segmental, allogenic cortical bone grafts was investigated in 15 rabbits using a 2-cm ulnar diaphyseal defect. Five different groups of bone grafts were evaluated: 1) unperforated undemineralized, 2) perforated undemineralized, 3) unperforated demineralized, 4) perforated demineralized, and 5) perforated demineralized grafts enclosed by silicone rubber (Silastic) sheets. There were 3 animals in each group. At 18 days, the study was terminated, and the implants were examined using radiographs and qualitative histologic preparations. We observed that healing of perforated demineralized bone was superior to unperforated demineralized bone, that undemineralized bone was partially sequestered in reactive lacunae, and that perforations in demineralized bone became centers of osteoinduction. Demineralized bone sterilized with ethylene oxide by this method vigorously formed new bone. PMID- 1590054 TI - Early intensive treatment of clubfoot. 75 feet followed for 6-11 years. AB - 47 consecutive children with 28 bilateral and 19 unilateral clubfeet were treated during the neonatal period according to a strict protocol including physiotherapy and bracing from the first 2 weeks of life; further, in most of the children, an operation was performed at 3 (2-5) months of age. Physiotherapy was continued during the first year of life and bracing for 3 years. 27 feet had repeat operations. No peroperative or postoperative complications were seen. At follow up at aged 8 (6-11) years, the cosmetic result was good in 62 feet, acceptable in 12 feet, and poor in 1 foot, whereas the functional result was excellent in 51 feet, good in 21 feet, and fair in 3 feet. The radiographs showed a higher lateral talocalcaneal angle in the control feet than in the treated feet; but in other radiographic aspects, no differences were seen. The need of a secondary or even tertiary operation did not indicate a poor result. PMID- 1590055 TI - McBride's operation for hallux valgus. A 2-11-year follow-up of 46 cases. AB - During a 10-year period, 46 feet with hallux valgus in 36 patients were operated on a.m. McBride. At the follow-up examination a median of 9 (2-11) years after the operation, a reduction in the hallux valgus angle from 32 degrees to 26 degrees and in the intermetatarsal angle from 13 degrees to 10 degrees was found; but on analyzing the single parts of the operation, we found that the result was only significant in those patients that had had the original procedures done, i.e., tenotomy and reattachment of the conjoined tendon, lateral capsulotomy, and lateral sesamoidectomy. McBride's operation for hallux valgus should be performed as described by the originator of the method. PMID- 1590056 TI - Surgery for multiple myeloma of the spine. A retrospective analysis of 12 patients. AB - We report on 12 surgically treated patients with myeloma of the spine. Pain relief was obtained in all the patients. Paraparesis was present in 5 patients. All 12 patients subsequently became ambulatory. The average postoperative survival was 2.3 years. Eight patients, all without symptoms from the treated lesion, survived for more than 1 year. Our experience suggests that surgical treatment of multiple myeloma of the spine may be rewarding. PMID- 1590057 TI - Sensory innervation of human thoracolumbar fascia. An immunohistochemical study. AB - We have studied the human thoracolumbar fascia by using antiserum against neurofilament protein (NFP) and S-100 protein to identify sensory nerve fibers and their endings. Seven surgical specimens from 7 patients were studied with light microscopy. In addition to free nerve endings, two types of encapsulated mechanoreceptors (Ruffini's and Vater-Pacini corpuscles) were identified. These findings support the hypothesis that the thoracolumbar fascia may play a neurosensory role in the lumbar spine mechanism. PMID- 1590058 TI - Determinants of osteoporotic thoracic vertebral fracture. Screening of 57,000 Finnish women and men. AB - A population sample of 27,000 Finnish women and 30,000 men was studied for the presence of a thoracic vertebral fracture. In both sexes, the prevalence of such fractures increased with age: after 40 years of age in the men and after 55 years of age in the women. The interaction of sex and age was significant, and even when the other determinants were adjusted for. In the women aged 35-44, 55-64, and 75 years or more, the prevalence per 1,000 was respectively 2.4, 5.1, and 29, and in the men in the corresponding age groups 5.2, 15, and 28. A previous history of trauma was a fracture determinant in both sexes. In the men, but not in the women, there was an increased risk of fracture when there was a history of tuberculosis and/or peptic ulcer, and in current smokers. Thus, contrary to observations on extremity fractures, the men had an increased risk of sustaining a thoracic vertebral fracture compared with the women. This may reflect differences in the development of osteoporosis in the axial skeleton versus the appendicular skeleton. PMID- 1590059 TI - Trapezius muscle changes unrelated to static work load. Chemical and morphologic controlled studies of 22 women with and without neck pain. AB - From a cross-sectional study of 82 women who were engaged in assembly work that involved static muscle loading of the shoulder muscles, 11 cases with complaints of neck tension (all except 1 arising at work) and 11 individually matched, exposed control cases without neck pain were studied. In addition, 10 matched, unexposed control cases were studied. Upon histochemical examination and study of the trapezius muscle, morphologic changes of type ragged red fibers were found in 8/11 neck-pain cases, in 7/11 exposed controls, and in 4/10 unexposed controls. The pathologic and clinical importance of rare, ragged red fibers in the trapezius muscle thus seems uncertain. PMID- 1590060 TI - Locomotion status and costs in destructive rheumatoid arthritis. A comprehensive study of 82 patients from a population of 13,000. AB - Clinical manifestations (locomotion score) and annual costs were studied in a population-based cohort of 82 patients with rheumatoid arthritis fulfilling five to eight American Rheumatological Association's (ARA) criteria. The total costs were SEK 4.9 million: respectively 56 and 44 percent direct and indirect costs. The costs were correlated with total, as well as subjective and objective, locomotion scores, which assess separately impairment, disability, and handicap from the disease (WHO 1980). Patients below 65 years had higher costs predominantly as an indirect cost due to loss of work-than older patients. Elderly rheumatoid arthritis (RA) patients had a low score and high costs for medical and social services' care, but they had no indirect costs. Patients with a low locomotion score had received previous hospital treatment averaging 89 days. The need of hospital treatment was strongly correlated with low locomotion score. The mean annual patient's costs were about SEK 60,000, but above this for younger patients. When compared with patients with a mild affliction (score 91 100), patients with moderate manifestations, i.e., with a score of 70-90, had five times higher costs, whereas those with severe manifestations, with a score below 50, had 20 times higher costs. PMID- 1590061 TI - Incidence of Colles' fracture in Uppsala. A prospective study of a quarter million population. AB - In a prospective study in Uppsala County (Sweden), certain characteristics of distal forearm fractures (DFFs) were investigated during a 1-year period in a mixed rural-urban population comprising all 214,000 persons above the age of 15 years. During the study period, 625 DFFs occurred, with a female/male ratio of 3.2:1. There was an age-related increase in DFFs among females that started as early as 40 years of age. In the males the incidence of DFFs was constant up to 70 years of age, and thereafter there was only a slight increase. The annual incidence of DFFs for women above aged 70 years was 115/10,000 and that for men 29/10,000. PMID- 1590062 TI - Epidemiology of scaphoid fractures in Odense, Denmark. AB - During a 7-year period, 273 scaphoid fractures were diagnosed in the approximately 175,000 residents of the municipality of Odense. The average annual incidence of scaphoid fracture was 8 per 100,000 women and 38 per 100,000 men, predominantly in young persons. The cause of injury was a fall in 69 percent and a blow in 28 percent. PMID- 1590063 TI - Spondylodiscitis after percutaneous discectomy. A case diagnosed by MRI. PMID- 1590064 TI - Bone cyst in the cervical spine due to secondary amyloidosis. A case report. AB - A patient who had been on hemodialysis for 20 years developed an amyloid bone cyst in the cervical spine. The cyst collapsed resulting in neurologic damage to the cervical spinal cord. He was known to have high circulating levels of beta-2 microglobulin. PMID- 1590065 TI - Compression of the ulnar nerve by an aneurysm. A case of late complication after a supracondylar fracture. AB - A 26-year-old man with a history of a supracondylar fracture of the left humerus 10 years ago had weakness and tingling of the fourth and fifth fingers of the left hand due to ulnar-nerve entrapment confirmed by electromyography. Angiography revealed complete obstruction of the brachial artery at the elbow and an aneurysm in the ulnar collateral artery at the medial epicondyle of the humerus. After reconstruction of the brachial artery and resection of the aneurysm, recovery was uneventful. Electromyography 6 months postoperatively was normal. PMID- 1590067 TI - The bloodless field. PMID- 1590066 TI - Cemented versus cementless hip arthroplasty. A review of prosthetic biocompatibility. AB - The fibrous interface tissue between hip prostheses and surrounding bone is often morphologically and functionally synovial-like. The fibroblast is the major cell type; but also giant cells and macrophages are present, and their numbers are increased in the occasional adverse-type host reaction to the prosthesis. Adverse lytic reactions are often associated with methylmethacrylate debris, whereas in cementless cases, polyethylene and metallic (titanium) wear debris seem to cause adverse reactions. Osteoblasts, osteoclasts, and mesenchymal collagenase secreted by fibroblasts and macrophages play an important role in the process of prosthetic loosening. Methylmethacrylate is immunologically relatively inert, while it induces inflammatory mononuclear-cell migration. Both cemented and cementless prostheses cause a foreign-body type host response, including adaptive and reactive processes. This response includes the formation of fibroblast-like B type lining cells, which are able to synthesize and secrete hyaluronate. Material surfaces of hip arthroplasty components also provide a unique environmental niche to which staphylococcal strains adhere and colonize. Antibiotic resistance is related to the material colonized rather than to the presence of an exopolysaccharide barrier; organisms bound to polyethylene and methylmethacrylate are more resistant than organisms that are bound to stainless steel. An understanding of prosthetic biocompatibility requires an appreciation of tissue cell, bacterial cell and host defense-system response to biomaterials. The site of implantation is a stage on which the "players" (bacteria, host cells, and organic moieties) interact and compete, and before which the host is a "responsive audience." PMID- 1590068 TI - [Surgical treatment of uretero-vaginal fistulae caused by gynecologic surgery]. AB - The present paper is a review of 71 cases of uretero-vaginal fistulae secondary to pelvic surgery which were treated in the Urology Unit of our hospital. Surgical management of these fistula intrinsically depends on their number, location and severity. The results obtained by the different techniques were analyzed, emphasizing their merit when using the Turner-Warwick technique (uretero-cystoneostomy on psoic bladder) and any urodynamic troubles this technique can bring about when used bilaterally in patients from radical gynaecological surgery. PMID- 1590069 TI - [Idiopathic retroperitoneal fibrosis: combined steroid and endourologic treatment]. AB - Review of 7 patients with idiopathic retroperitoneal fibrosis (IRF), treated with a combination of corticosteroids (6-methyl-prednisolone) and endourological procedures. The presentation symptom was lumbar pain in all 7 cases. Mean creatinine (Cr) levels were 5.4 mg/dl, with mean erythrocyte sedimentation rate (ESR) of 114. Three (43%) patients were positive to rheumatoid factor (RF) and had raised IgG. Definite diagnosis was achieved in all cases by CAT, including puncture biopsy in 1; all 7 (100%) cases were bilateral. With an average follow up of 3 years, clinical evolution is satisfactory in all 7 cases. Mean control Cr is 1.2 mg/dl and mean ESR 19. CAT showed disappearance of fibrotic plaque in all cases. One patient relapsed when maintenance therapy was discontinued but responded again to a new therapy course. No steroid therapy-related complications were seen. The association of conservative steroid therapy and endourological procedures is a very low morbidity, sensible alternative in the management of benign retroperitoneal fibrosis where CAT and MNR are the primary diagnostic techniques. PMID- 1590070 TI - [Renal transplantectomy]. AB - During the first ten years (1981-1990) of our organ transplantation program a total of 395 Renal Transplants (RTx) have been carried out in our Unit, 90 of which in 88 patients had to be subsequently transplantectomized. In 32 of them the reason was acute rejection (35%) including 7 renal rhexis, and in 30 chronic rejection (33%) (1 rhexis). There were 22 (24%) (1 rhexis) vascular complications leading to such procedure. The technique was chosen mainly depending on the amount of time elapsed between transplantation and transplantectomy, performing 47 subcapsular and 43 extracapsular manoeuvres. The complications developed were 7 (7.7%), mostly haemorrhagic. Our attitude when faced with non-functioning grafts due to chronic rejection is the complete withdrawal of immunosuppression performing transplantectomy only in the event of arterial hypertension or in the presence of symptoms of acute rejection overimposition. PMID- 1590071 TI - [Value of CAT staging in renal adenocarcinoma. Correlation with anatomo pathologic findings]. AB - On a total of 128 renal adenocarcinomas diagnosed in our Unit between January 1975 and August 1990, the data provided by CATs carried out in 85 of them was compared with that from surgical and anatomo-pathological findings. The precision in both the diagnosis and the tumour staging was determined, evaluating the involvement of perirenal, nodular, venous and neighbouring structures fat. The diagnosis of renal adenocarcinoma was made correctly in 96% cases. With regard to staging, maximal precision was achieved in the involvement of adjacent structures and vena cava, followed by the renal vein, perirenal fat and lymphatic nodes, in this order. We conclude that CAT provides a high diagnostic reliability, permitting with a single study the determination of the most defining parameters of renal cancer staging. PMID- 1590072 TI - [Urologic neoplasms in AIDS]. AB - Report on 2 cases of urological neoplasia in HIV positive patients. The first one is a renal adenocarcinoma in a heroin-abuser patient, of a type we have only found mentioned in the literature in 4 other cases. The second case was a disseminated Kaposi's sarcoma, the first symptom being a scrotum impairment and the biopsy suggested the diagnosis. This is believed to be an interesting communication considering the increasing number of anti-HIV antibodies carriers seen in our Units. PMID- 1590073 TI - [Renal transplantation in patients over 50 years old: our experience with 58 cases]. AB - Retrospective analysis of the results from corpse renal transplantation, under immunosuppressive therapy with cyclosporin in a group of 58 elderly receptors (greater than or equal to 50 yr). The results are compared with those obtained in 152 receptors under 50 year of age transplanted during the same period of time (1984-1988). No statistical differences were seen between both groups regarding immunosuppressive therapy, number of transfusions, HLA histocompatibility, number of transplantations and percentage of hypersensitive patients. Incidence of rejection is significantly higher in the younger patients group, as well as graft loss due to immunological reasons. Mortality was significantly higher in the elderly group. Actuarial survival of the graft after two years is similar in both groups. It is concluded that in the era of cyclosporin, the receptor's age should still be considered a risk factor and, therefore, that maximum precautions should be taken in order to detect any additional risk factor within this group in a strategy to improve their survival. PMID- 1590074 TI - [Enterocystoplasty in the treatment of myelodysplastic bladder]. AB - Over the last five years 18 myelodisplastic patients with neurogenic bladder have undergone in our Unit a surgical operation consisting in vesical enlargement with patch-like bowels. They all had incontinence and urinary infections and there was a high percentage of pyelonephritic events. A report on the results from 13 patients whose post-operative evolution is longer than one year is included. Eleven patients were completely and two partially continent; pyelonephritic events have ceased or became more spaced; renal function, assessed by UIV is within normal values or shows improvement in 22 renal units while only one patient, out of 11 pre-operative cases, continues having vesico-renal reflux. PMID- 1590075 TI - [Infiltrating bladder carcinoma with metastatic lymph node involvement: radical treatment and survival]. AB - Presentation of the results obtained from the study of 64 patients with T2-4 stage vesical carcinoma, treated with radical cystectomy, local lymphadenectomy, with and without complementary radiotherapy, with and without neoadjuvant chemotherapy. The univariate study of 19/64 patients with microscopic nodular disease revealed a significant relationship with the pathological stage but not with the clinical stage. The multivariate study demonstrated that the most relevant prognostic factors are a decrease in tumoral stage (P) and the presence of vascular and/or lymphatic involvement in the TUR-biopsy. The analysis of survival confirms the poor prognosis of patients with metastatic nodular involvement, in spite of the association of pelvic radiotherapy or neoadjuvant chemotherapy to the treatment. PMID- 1590076 TI - [Treatment of urogenital tuberculosis with ofloxacin. Preliminary study]. AB - Ofloxacin is a new fluoride quinolone which has been shown to be active both in vitro and in vivo against Mycobacterium tuberculosis. This prospective study presents the results obtained with a new protocol for the treatment of genito urinary tuberculosis. The comparison drugs were Ofloxacin 200 mg every 12 hours for 6 months, Rifampicin 600 mg every 24 for 3 months and Isoniazid 300 mg every 24 hours for 3 months. The results, were clinically and microbiologically good. It is concluded that this new drug should be a valid alternative to the traditional therapy. PMID- 1590077 TI - [Treatment with ESWL of lithiasis in the transplanted kidney]. AB - Report on one case of lithiasis in a transplanted kidney treated successfully with extracorporeal shockwave lithotrity. This is considered to be the choice therapeutical method when there are no bone interposition or urinary tract obstruction which may preclude the correct removal of lithiasis fragments. PMID- 1590078 TI - [Diagnosis and treatment with ureterorenoscopy of ureteral obstruction caused by papillary necrosis]. AB - Increasing use of endourological procedures to establish a diagnosis of pyeloureteral lesions detected as a repletion deficiency during urographic study, which when they are obstructive, affect the upper urinary tract. The present report describes the use of ureterorenoscopy as a diagnostic and therapeutic procedure for the ureteral obstruction occurring in a patient with papillary necrosis secondary to analgesics abuse. The papilla was indwelt in the right distal ureter causing obstruction and symptoms of renal colic and septicemia. PMID- 1590079 TI - [Testicular torsion. The first manifestation of polyorchidism]. AB - Presentation of a new case of polyorchism, its first clinical evidence being a picture o acute scrotal bag requiring surgical examination. Review of current status with regard to diagnostic and therapeutic procedures. PMID- 1590080 TI - [Metastasis of prostatic origin in periorbital soft tissues]. AB - Appearance of orbital metastatic (OM) neoplasia is the most frequent cause of eye tumour; however, its incidence related to prostatic carcinoma (PC) is rare, primarily when there is sole infiltration of the periorbital soft tissue (STOM). The paper describes the case of a patient diagnosed with PC presenting proptosis and diplodia as first spread symptoms. The rarity of STOM of the prostatic carcinoma prompted the diagnosis to be seen sceptically until immunohistochemical confirmation was obtained. An analysis is made of various features of interest regarding the grading of OM, clinical incidence and diagnostic methods. The singularity of the present case, affecting only the periocular soft tissues is illustrated. Finally, the situations requiring orbital biopsy in order to avoid a second neoplasia are analyzed. PMID- 1590081 TI - [Beneficial effect of oxygen-free radical blockers in experimental kidney transplantation in rats]. AB - The clinical potential of free radical (OFR) ablative therapy is dependent upon the proportion of the total injury caused by the reperfusion mechanism compared with the proportion resulting from ischemic injury itself. Prostaglandin cascade can both activate and be activated by OFR. AIM: to investigate the influence of different periods of cold ischemis in renal tissue (cortex and medulla) regarding superoxide dismutase (S.O.D.) activity, the amount of erythrocyte trapping and prostaglandin synthesis. Also, to evaluate the effect of exogenous S.O.D. in the prevention of reperfusion injury. MATERIAL AND METHODS: 48 Lewis male rats (200-250 g) received renal isografts (RTx) preserved in Collins solution at 4 C for different periods: control group (8) non operated; group I (8) immediate RTx; group II (8) 12 hrs; group III (8) 18 hrs; group IV (8) 12 hrs+S.O.D. (13 mg/kg e.v.); group V (8) 18 hrs+S.O.D. (13 mg/kg e.v.). Before reperfusion all recipients received 1 ml of 51-Cr labelled erythrocytes. After 15 min. reperfusion grafts were removed and samples (cortex and medulla) obtained for measuring trapping of erythrocytes. S.O.D. activity and prostaglandins (PGe2, TxB2, 6-Keto-PGF1). RESULTS: A strong correlation was found between the duration of cold ischemia and the amount of trapping both in cortex and in medulla. S.O.D. administration induced a significant drop of trapping. In non-operated rats S.O.D. activity in cortex was two fold medulla content. However, after reperfusion, a significant decrease in cortex was found in all groups. S.O.D. administration raised S.O.D. activity in cortex similar to control values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590082 TI - [Skin lesions of the male genital organs in urologic practice]. PMID- 1590083 TI - [Retroperitoneal fibrosis]. AB - Review of 8 patients with retroperitoneal fibrosis treated in our unit, 7 between 1985 and 1990 and one secondary to chronic use of non-steroidal anti-inflammatory agents diagnosed in 1980. In five patients no underlying reason was found and the remaining three were considered to be secondary (two to drugs and one to pelvic radiotherapy). Diagnostic and therapeutic approaches as well as patient's evolution are analyzed, also reviewing the existing literature. PMID- 1590084 TI - [Acquired cystic renal disease. Association with hypernephroma]. AB - Emergence of multiple bilateral renal cysts observed in patients undergoing periodic haemodialysis is 40%. The pathology, known as Acquired Cystic Renal Disease (A.C.R.D.) presents a high association to renal cancer. Two cases of A.C.R.D. and their association with hypernephroma, one resulting in secondary retroperitoneal haemorrhage and the other in intracystic haemorrhage, are presented. Forms and diagnosis are analyzed, insisting upon the need of monitoring the patients in haemodialysis from the point of view of tumour emergence. PMID- 1590085 TI - [Review of 45 cases of renal oncocytomas published in our country, and presentation of 2 new cases]. AB - A review is made on the characteristics presented by the 45 cases of renal oncocytomas published in the specialized literature in our country, which are compared to major publications on the subject in the international literature in which a recent review reports 200 cases. Also, two new cases are presented. These tumours are included within the 17 benign renal tumours accumulated in our centre (11.7%) accounting for 2.27% of all renal tumours diagnosed by our group. The renal oncocytoma opens a significant controversy with regard to its definitive identity and, therefore, with regard to its possible therapy whether radical or conservative. PMID- 1590086 TI - [Is the early diagnosis of prostatic cancer possible using transrectal echography?]. AB - One of the major challenges of using prostate transrectal ultrasound scanning as a procedure to diagnose through images is the theoretical possibility of reaching an early diagnosis of prostate cancer. This paper compiles the author's experience in this field. Based on 142 established diagnosis of prostate cancer since 1984, the conclusion being reached is that prostate cancer has no pathognomonic signs, and therefore it is impossible to make an early diagnosis just by using the images obtained with transrectal ultrasound scanning. This procedure could be used, however, to select patients with scan abnormalities (Alarm signs) who should have a biopsy performed. The support of ultrasound-led transperineal biopsy of the prostate is currently indispensable to achieve an early diagnosis. This paper suggests that a biopsy should be done at the appearance of just one alarm sign, although this may involve a large number of cancer negative biopsies. The almost null incidence of complications from transperineal biopsies enhances this reasoning. PMID- 1590087 TI - [Infiltrating carcinoma of the bladder: preliminary results of multidisciplinary protocols with radiotherapy and neoadjuvant chemotherapy]. AB - Report on the evolution of a series of 64 patients with T2-4 N0-3 M0 infiltrant transitional carcinoma of the bladder, treated with TUR and radical cystectomy (28/62) or intra-operative radiotherapy (IOR) 15 Gy and external radiotherapy 40 Gy prior to cystectomy (34/62). The last group including 24 patients which received neo-adjuvant chemotherapy. Seventy percent (15 p0N-, 5 p0N+, 1 p1N-, 3 p1N+) patients treated with radiotherapy, with and without chemotherapy, had local response. Considering just the group which received IOR, external radiotherapy and co-adjuvant chemotherapy (24/34), the local response accounts for 79% (10 p0N-, 5 p0N+, 1 p1N-, 3 p1N+). Current survival of the group receiving concomitant multiple therapy is 92 +/- 5%, 75 +/- 9% and 57 +/- 11% at 1, 3 and 5 years; for equal intervals current survival of the group undergoing cystectomy is 57 +/- 9%, 46 +/- 9% and 40 +/- 10% (p = 0.02). The univariate analysis has confirmed that stage decrease is significantly more frequent in the group receiving radiotherapy with and without chemotherapy (p less than 0.001). Such a decrease significantly biased survival (p = 0.001). In the multivariate analysis, the variables with greater prognostic power were pre-surgical renal function (p less than 0.001), use of radiotherapy (p less than 0.001) and surgical complications (p less than 0.001). Preliminary results show a very high local response to multiple therapy which has been translated so far in increased survival. PMID- 1590088 TI - [Bladder carcinoma and brain metastases before systemic chemotherapy]. AB - Clinico-pathological study of six patients with cerebral metastasis from vesical carcinoma with no prior administration of systemic chemotherapy. In two cases the symptoms of intracranial mass were the initial reason for infiltrant vesical carcinoma examination. Despite the rarity of such occurrence, the possibility of vesical tumours showing in such a way must be taken into account. The singularity of cerebral metastatic seeding throughout the natural history of a vesical neoplasia is analyzed. Also, a review is made of the factors hypothetically responsible for the increase of cerebral metastasis establishment following current chemotherapy. PMID- 1590089 TI - [Prostatic abscess--new diagnostic and therapeutic guidelines]. AB - Five prostatic abscesses treated in our Unit over the last three years (1988, 89, 90) are presented. Both the mode of presentation and symptoms as well as the course of treatment followed (three percutaneous drainage through the perineum, lead by ultrasound scanning, one endoscopic abscess incision with Collins' knife and one resolved with antibiotics subsequently needing TUR of the prostatic adenoma) are reviewed. The change of attitude in the treatment of prostatic abscesses (Ultrasound-lead percutaneous drainage) and the major usefulness of ultrasound scanning for diagnosis, treatment and subsequent follow-up are emphasized. PMID- 1590090 TI - [Trigono-cervico-prostatic incision]. AB - Trigone-cervico-prostatic incision is a surgical alternative in the treatment of urinary obstruction induced by small size prostate. Twenty-three patients were treated in our unit with this procedure, 17 because they were carriers of small size prostate and 6 because they were high risk surgical patients in which the simplicity and swiftness of this technique were essential. Good results have been obtained both clinical and in urological flow in 95.7% cases. The only complication was one stenosis of the urethra requiring internal urethrotomy but there were no cases of vesical cervix contracture or urinary incontinence. Average follow-up was 12.5 months. It is concluded that this is a valid, low morbidity alternative that can be offered to patients with small sized and symptomatic prostate. PMID- 1590091 TI - [Primary retroperitoneal hydatidosis]. AB - The case of a primary retroperitoneal hydatidosis in a 62 year-old patient found accidentally during an haematuria study is presented. Both the possible extraperitonization mechanisms and efficacy of ultrasound scanning and percutaneous puncture in the etiological diagnosis in cases of retroperitoneal mass are evaluated. PMID- 1590092 TI - [Gangrenous cystitis induced by giant bladder calculus]. AB - Presentation of one case of gangrenous cystitis or vesical gangrene induced by the presence of a large vesical calculus in a patient with neurogenic bladder. Remarks on the patho-etiology, symptoms and treatment of this rare entity entailing a truly surgical emergence. PMID- 1590093 TI - [Pyeloduodenal fistula, secondary to lithiasic pyonephrosis]. AB - Report on one patient presenting pyelo-duodenal fistula secondary to pyonephrosis by an obstructive calculus in lumbar ureter, treated conservatively with percutaneous nephrostomy. PMID- 1590094 TI - [Bladder involvement in non-Hodgkin's lymphoma. Diagnosis and therapeutic response]. AB - Presentation of one case of non-Hodgkin lymphoma (NHL) in a 76 year-old, female patient presenting with giant abdominal mass, secondary tumoral vesical infiltration and bilateral obstructive uropathy diagnosed by UIV, CAT and cystoscopy-biopsy. Transitory deobstruction with 'pig-tail' catheter allowed administration of therapy with multiple chemotherapy with excellent response. The radiological, endoscopic and histopathological findings, as well as the incidence of the uncommon vesical pathologies are reviewed. PMID- 1590095 TI - [Paratesticular adenomatoid tumor: clinico-pathologic study]. AB - Display of the clinico-pathological correlation of three cases of adenomatoid tumour (AT) of the male reproductive organs. From the anatomo-pathological point of view we observe the architectural patterns traditionally described, and discuss their controversial mesothelial origin. From the clinical point of view we highlight the benignancy of the process, often underdiagnosed, as well as its association to post-inflammatory hydrocele in one case. Such coincidence could favour the assumption that inflammation plays a decisive role on the production mechanism. PMID- 1590096 TI - [The original of the "Tratado de Urologia" by Francisco Diaz. Lost during the fire of the Monastery of El Escorial in 1671?]. AB - The publication of the Treaty of Urology of Francisco Diaz towards the end of the sixteenth Century, was a milestone in the History of medicine. The originality and precociousness of his doctrine entailed a true revolution in the genesis of medicosurgical literature, considering that the text constitutes an inspired anticipation to the specialization age. Ever since the last century, all historians and annotators of this work have asked themselves whether there was an earlier edition to that of 1588 since the title "Newly printed treaty ..." invites such a inference. So far, every investigation searching for the original or a copy of the first edition have been in vain. This paper, based on documents and old works from the Archive of Protocols in Madrid, Library of the Royal Palace and Library of El Escorial Monastery, reveals certain data until now unpublished on the destiny of most of the copies belonging to the second edition presented and brings into light old references on which account is given that the original "Treaty of Urology" by Francisco Diaz, considered to be a Sixteenth Century Codex was lost in the fire of the El Escorial Monastery in 1671. PMID- 1590097 TI - A review of the effects of long-acting progestogen-only contraceptives on ovarian activity. AB - Progestogen-only contraception acts mainly by blocking cervical mucus and preventing sperm penetration through it does have a variable pattern of contraceptive effects on the endometrium and ovary. In contrast with the complete suppression of ovarian function with combined pill or injectable use, a variable degree of endocrine activity is demonstrated in women choosing a long-acting progestogen-only contraceptive. This degree of suppression of ovarian activity explains the decrease in systemic side-effects, the rapid resumption of ovulation and recovery of fertility following the discontinuation of the method. New delivery systems of progestogens, the vaginal ring and implant, offer better and more consistent contraceptive effects. PMID- 1590098 TI - Carbohydrate metabolism after three months of using a gestodene-containing monophasic oral contraceptive. AB - Carbohydrate metabolism was prospectively evaluated in twenty-one normal women prior to and during their use for three months of a monophasic oral contraceptive containing the progestin gestodene plus ethinyl estradiol. The women had a three hour oral glucose tolerance test using a 75 gram glucose load, measuring serum glucose and insulin levels. The results demonstrate no significant changes in either of the carbohydrate metabolic indices between the two tests. These data support the safety of this new progestin-containing contraceptive. PMID- 1590099 TI - The effect of low-dose oral contraceptives and Norplant on blood pressure and body weight of Nigerian women. AB - Blood pressure (BP) and body weight were assessed at entry, 6 months and 12 months of use in a prospective study of 117 and 76 women using low-dose oral contraceptives (LD-OCs) and Norplant, respectively. The results showed that mean systolic BP (mmHg), diastolic BP (mmHg) and weight (kg) for LD-OCs and Norplant at entry, 6 months and 12 months, respectively, were not significantly different. During the one year of use, the study found that moderate increase in BP occurred at the same frequency as reduced BP, and that observed variation in BP was within a narrower range in Norplant users compared with LD-OC users. PMID- 1590100 TI - Serum SHBG levels during normal menstrual cycle and after insertion of levonorgestrel-releasing IUD. AB - Daily serum sex hormone binding globulin (SHBG) levels were measured during normal ovulatory menstrual cycles in ten women between the ages of 23 and 34 by the method of precipitation with ammonium sulfate. The results showed that the mean SHBG levels in a cycle were quite different among individuals, but that the SHBG levels were constant during a certain menstrual cycle. Neither SHBG peaks on day LH-0 (52.64 +/- 19.89 nmol/L) (x +/- SD) nor the mean SHBG levels between the follicular phase (57.10 +/- 17.64 nmol/L) and luteal phase (64.75 +/- 23.42 nmol/L) show any significant differences. The correlations between the mean SHBG levels and the mean concentrations of progesterone (P), estradiol (E2) and androstenedione during the menstrual cycles were insignificant, whereas the mean SHBG levels during the follicular and luteal phase and on LH-0 day were significantly correlated with the mean concentrations of testosterone (t = 0.474; p less than 0.05). In ten women between the ages of 25 and 34, serum SHBG, E2, P, and levonorgestrel (LNG) levels were measured once on day 20-21 of the pretreatment cycle and 3 times/week during the 1st, and 2 times/week during the 6th treatment cycle after insertion of a levonorgestrel-releasing IUD (LNG-IUD). The mean value of SHBG in the pretreatment blood samples (62.09 +/- 23.09 nmol/L) was higher than that after insertion of the LNG-IUD (41.82 +/- 20.50 nmol/L), though the difference was not significant (p greater than 0.05). The correlation between LNG and SHBG was highly significant (r = 0.89, p less than 0.01). The significance of this correlation and the degree of suppression of ovarian function are discussed. PMID- 1590101 TI - Sources of information, experiences and opinions on sexuality, contraception and STD protection among young Swedish students. AB - The aim of the investigation was to study sources of information on sexuality, contraceptives and STDs among young people as well as their experiences of and opinions on the matter. A questionnaire was distributed to 192 high-school pupils in the Stockholm area. The mean age of the participants was 17.4 years. The majority stated that school teachers and individual reading are the best sources of information. Female students more often relied on friends and family members than male students. Among those who had had their sexual debut, many stated that condom use was hard to practice. PMID- 1590102 TI - When does exposure to agent X cause disease Y? AB - The concept of 'cause' between exposure to agent X and the subsequent development of disease Y is reviewed briefly in terms of how it is used in experimental and clinical medicine, statistics and epidemiology, and in law. Some of the interrelationships of the definition of cause by these disciplines are considered. PMID- 1590103 TI - Long-term evaluation of the clinical performance of the TCu200B and the TCu380A in Campinas, Brazil. AB - The clinical performance of the TCu200B and TCu380A was evaluated by life table analysis in a cohort of women who wore an IUD from July 1979 to July 1982. This paper presents the results up to five years of use. No significant differences in age and parity were found between the users in the two groups. Overall performance was very good with both models. The cumulative continuation rate was 83.6, 60.9 and 46.1 at one, three and five years with the TCu200 and 84.0, 64.7 and 49.3 with the TCu380A in the same periods. Differences between both IUDs were not significant. The pregnancy rate was lower with the TCu380A and reached statistical significance from the fourth year on. The authors conclude that both IUDs presented very good performance, the TCu380A being more effective, the only significant difference observed. PMID- 1590104 TI - Clinical experiences with MLCu250 and MLCu375 IUD. AB - The paper summarizes the author's ten-year experience with 1446 interval insertions of the MLCu250 standard-type device, and makes comparison between the first two-year results of this and the MLCu375 IUD. The 120th month was completed by 106 MLCu250 users, and the cumulative woman-months of use (wmu) were 78,078. At the end of the second year, 976 patients were at risk in this group, representing a total of 28,097 wmu. From the initial 224 MLCu375 IUD cases, 160 (2,151 wmu) and 93 (3634 wmu) were eligible for life-table calculation at the end of the first and the second year, respectively. The overall performance was evaluated by net and gross cumulative and yearly specific rates as suggested by Tietze. These figures are detailed by the article. Based on this evaluation, two statements are made: (1) the MLCu250 standard-type device has a good overall performance and a longer life span than was previously expected; (2) the first two-year results with the MLCu375 are more favorable (lower termination rates, higher continuation) than the MLCu250. PMID- 1590105 TI - Self-induced abortion--the peril is still real. AB - A new immigrant from Romania tried to induce abortion by intrauterine self administration of hypertonic sucrose at 7 weeks' gestation. Complete abortion did not occur and bleeding, infection and pregnancy residua persisted for 13 weeks. Evacuation by uterine curettage had failed, but a second curettage under real time sonographic guidance was successful. Self-induced chemical abortions are rarely encountered in modern medicine. However, elevation of the iron curtain and mass immigration may increase the frequency of self-induced abortions in Western countries. Since the management, course, and outcome of each type of self-induced abortion are somewhat different, the pertinent differentiation is between chemical and mechanical and between various agents used for chemical-induced abortions. Mechanical abortions are best treated 12 to 24 hours after antibiotic therapy, while in chemically-induced abortion early evacuation of the uterus is indicated. PMID- 1590106 TI - Lesions of skin and brain: modern imaging of the neurocutaneous syndromes. AB - The neurocutaneous syndromes, or phakomatoses, are a diverse group of disorders affecting the skin and CNS. This review highlights some important but lesser known aspects of the more common phakomatoses while concentrating on rarer and more recently discovered syndromes. The roles of newer imaging techniques such as contrast-enhanced MR imaging and three-dimensional CT in the evaluation of these disorders also are discussed. PMID- 1590107 TI - Value of MR imaging in the evaluation of chronic infiltrative lung diseases: comparison with CT. AB - The value of MR imaging was compared with that of high-resolution CT in assessing chronic infiltrative lung disease in 25 patients. The cases included nine patients with usual interstitial pneumonia, six with sarcoidosis, four with hypersensitivity pneumonitis, and six with miscellaneous conditions. The diagnosis was proved by biopsy (n = 17) or by means of clinical, laboratory, and radiologic criteria (n = 8). All patients had 1.5-T MR imaging and CT of the chest. Cardiac-gated T1-, proton density-, and T2-weighted spin-echo sequences were obtained. Initially, the MR images were assessed independently; later they were compared directly with the corresponding CT scans. In six patients, MR images and CT scans were obtained before open lung biopsy, and the images and scans were assessed prospectively. CT was superior to MR imaging in the anatomic assessment of the lung parenchyma and in showing fibrosis. However, areas of air space opacification (ground-glass opacities) were seen as well on MR as on high resolution CT. In the six patients who had open lung biopsy, areas of air-space opacification seen on MR and on CT corresponded to areas of active alveolitis or air-space infiltrates pathologically. Follow-up in six patients showed equal degrees of change in the air-space opacification over time on MR and CT. We conclude that, although MR imaging is inferior to high-resolution CT in the assessment of chronic infiltrative lung diseases, it may play a role in the assessment and follow-up of patients with air-space opacification. PMID- 1590108 TI - Anatomical lectures by Dr. William W. Keen. PMID- 1590109 TI - Swyer-James syndrome: CT findings in eight patients. AB - To determine the importance of chest CT findings in patients with Swyer-James syndrome (unilateral small lung with air trapping) and to compare these findings with those on chest radiographs and scintigrams, we reviewed the CT scans, chest radiographs, and scintigrams of eight patients with the syndrome. Radiographs showed unilateral hyperlucency in seven patients and bilateral asymmetric hyperlucency in one. CT showed that the hyperlucency was unilateral in only three and that hyperlucency in one. CT showed that the hyperlucency was unilateral in only three and that hyperlucent regions on radiographs contained patches of normal lung attenuation in five patients. Conversely, in four patients, CT also showed small hyperlucencies in regions considered normal on radiographs. These lucencies usually had poorly defined margins and irregular shapes (five patients), but sometimes were peripheral, wedge shaped, and sharply demarcated (two patients). CT also showed subtle abnormalities not visible on radionuclide scans in two patients. Air trapping in hyperlucent regions was confirmed by a lack of change in volume on expiratory CT scans in five cases. Bronchiectasis was found in only three patients. CT helps to exclude central bronchial obstruction, cysts, and vascular disease as causes of hyperlucency. By excluding central obstruction, CT may make bronchoscopy unnecessary in some patients. CT is more sensitive than radiographs and radionuclide scans in detecting hyperlucent regions and in showing their distribution. Our experience suggests that bronchiectasis is not a necessary component of the Swyer-James syndrome. PMID- 1590110 TI - CT findings in lymphangitic carcinomatosis of the lung: correlation with histologic findings and pulmonary function tests. AB - The purpose of this study was to analyze the CT findings in lymphangitic carcinomatosis and to determine how the abnormalities seen on CT correlated with histologic findings and the results of pulmonary function tests. Accordingly, we reviewed CT findings in 20 proved cases and correlated them with histologic findings and with results of pulmonary function tests (available in 11). Special attention was given to the extent and degree of thickening of the peripheral and/or axial interstitium as seen on CT. In 15 of 20 patients, CT scans showed marked thickening of axial interstitium and subtle or no thickening of peripheral interstitium (four diffuse and 11 localized). In three cases, CT showed marked thickening of both axial and peripheral interstitium (two diffuse and one localized). In two cases, CT showed marked thickening of peripheral interstitium and subtle or no thickening of axial interstitium (one diffuse and one localized). These CT findings correlated with the pathologic findings. Marked impairment of vital capacity and alveolar-arterial oxygen gradient was observed in three patients (one with diffuse and peripheral interstitial thickening and two with diffuse and both peripheral and axial interstitial thickening). We conclude that CT findings in patients with lymphangitic carcinomatosis are variable and that marked impairment of pulmonary function occurs in patients with diffuse and peripheral interstitial thickening. Marked impairment of pulmonary function can be predicted from CT findings. PMID- 1590111 TI - Summer-type hypersensitivity pneumonitis: comparison of high-resolution CT and plain radiographic findings. AB - Summer-type hypersensitivity pneumonitis is an immunologic disease that occurs only in Japan. It is a form of hypersensitivity pneumonitis in which the clinical symptoms appear in the summer and subside spontaneously in mid autumn. The purpose of our study was to determine the CT findings in this condition, to compare the CT findings with those on chest radiographs, and to assess the variations in the CT findings over time. Accordingly, high-resolution CT scans and chest radiographs of 15 patients with summer-type hypersensitivity pneumonitis were retrospectively studied. Seven patients had sequential CT examinations 18-37 days apart. The CT scans and chest radiographs were reviewed by two observers independently. CT findings included diffuse micronodules (n = 15), slightly elevated lung density (n = 13), and patchy air-space consolidation (n = 13). In one patient, the findings on a chest radiograph were normal, while CT showed parenchymal abnormalities. In two cases, follow-up CT showed micronodular abnormalities after findings on the chest radiograph had returned to normal. Our results show that high-resolution CT findings of summer-type hypersensitivity pneumonitis include pulmonary micronodules, increased lung density, and air-space consolidation. High-resolution CT appears to be more useful than plain chest radiographs in the evaluation of pulmonary parenchymal abnormalities in this condition. PMID- 1590112 TI - Thymoma with hypogammaglobulinemia (Good's syndrome): an unusual cause of bronchiectasis. PMID- 1590113 TI - Interventional procedures in diseases of the breast: needle biopsy, pneumocystography, and galactography. AB - This article discusses the roles of mammography-guided needle biopsy of the breast, pneumocystography, and galactography in further defining breast lesions that have been detected with mammography. For each procedure, indications for its use, proper technique, complications, interpretation, and role in clinical practice are described. Use of these procedures is warranted for some patients to provide detail beyond that available with mammography and sonography. PMID- 1590114 TI - The role of fine-needle aspiration and pneumocystography in the treatment of impalpable breast cysts. AB - Prior studies have suggested that the recurrence rate is lower in breast cysts treated by pneumocystography (injection of air into cyst cavities after cyst aspiration) than in cysts treated by fine-needle aspiration alone. To determine if this is the case for impalpable breast cysts, we reviewed the hospital records and mammograms of 38 women with 41 impalpable cysts. Mammograms obtained immediately after aspiration show that pneumocystography was successful in 18 and unsuccessful in 20 of the 41 cysts. Four cysts were excluded from the study: one cyst that recurred after aspiration and was sampled by biopsy and three cysts for which immediate post-aspiration mammograms were unavailable but which had recurred or persisted 3 years after aspiration. Review of follow-up mammograms made 4 months to 3 years after the aspiration showed that three (17%) of 18 cysts in the group with successful pneumocystography recurred and 11 (58%) of 19 cysts in the unsuccessful group recurred (p = .02). No difference was found in the number of recurrent cysts in relation to estrogen therapy or menopausal status. Our results indicate that impalpable breast cysts treated by pneumocystography are less likely to recur than are cysts treated by aspiration alone. PMID- 1590115 TI - Hidden costs of mobile mammography: is subsidization necessary? AB - Two major impediments to an effective mammography program are inaccessibility and cost. This article itemizes the expenses associated with providing a mobile screening program accredited by the American College of Radiology (ACR) during a 3-year period. Mobile Diagnostics Inc. established a mobile mammography service in April 1987. A 36-ft (11-m) van is staffed by two registered technologists. The unit includes on-board processing and educational videotapes. Analysis of expenses for the years 1988, 1989, and 1990 does not include interpretation fees. A total of 3522 patients were examined in 1988, 4232 in 1989, and 5005 in 1990. Fixed operating expenses in 1988 were $70/examination and variable expenses were $13/examination, resulting in an average total cost per examination of $83. Fixed costs in 1989 were $63, variable costs were $15, and total costs were $78 per examination. Fixed costs in 1990 were $55, variable costs were $14, and total costs were $69 per examination. Many third parties, including Medicare, are contemplating a global screening fee in the $50-$60 range. An average payment of $55 would require examination of more than 6500 patients a year or 28 patients a day to break even. Our experience suggests that some form of subsidization may be necessary to sustain a mobile mammography service at those reimbursement levels. PMID- 1590116 TI - Treatment of mesocaval shunt stenosis with a metallic stent. PMID- 1590117 TI - Peribiliary chloroma: a rare cause of jaundice after bone marrow transplantation. PMID- 1590118 TI - Cystic testicular mass caused by dilated rete testis: sonographic findings in 31 cases. AB - We reviewed the scrotal sonograms of 31 patients who had a testicular mass consisting of multiple small spherical or tubular anechoic structures in the region of the mediastinum testis. The median age of the patients was 62 years (range, 31-76 years). The abnormality was unilateral in 22 patients and bilateral in nine. Thirty-four (85%) of the 40 involved testicles had coexisting epididymal abnormalities: 32 with epididymal cysts and two with epididymitis. Follow-up sonograms were available in five patients and showed no change up to 4.5 years after the initial diagnosis. Surgical and histologic findings were available in one other patient and showed dilatation of the rete testis. The sonographic appearance and location of the lesions, the frequent presence of an epididymal abnormality, and the surgical and histologic findings in one case suggest that the lesion is due to dilatation of the rete testis, probably associated with obstruction in the epididymis. Recognition of this entity on sonograms may prevent unnecessary orchiectomy. PMID- 1590119 TI - Peyronie's disease: MR findings in 28 patients. AB - Induratio penis plastica (Peyronie's disease) is a chronic fibrotic process involving the penis. Proper treatment of the disease requires assessment of the degree of inflammation preceding or accompanying the fibrous Peyronie's plaques. Owing to its high tissue contrast and its multiplanar capability, MR imaging offers excellent visualization of penile anatomy. To determine the usefulness of MR imaging in the diagnosis and staging of Peyronie's disease, we used MR imaging with a surface coil to examine 28 consecutive patients with clinical evidence of the disease. Eighteen patients had contrast-enhanced MR imaging with gadopentetate dimeglumine. In seven patients who subsequently had surgery or biopsy, MR findings were correlated with histopathologic findings. On unenhanced images, fibrous plaques were shown in 20 patients. Enhanced MR images showed focal contrast enhancement around or within the plaques in seven patients. Images in three patients with plaques showed no enhancement. Images in five patients showed focal areas of contrast enhancement without evidence of plaques. Histologic studies demonstrated that the degree of contrast enhancement correlated with the extent of inflammatory cell infiltration. In two patients with unenhancing plaques on MR, histology confirmed the absence of inflammation. Our results suggest that MR imaging not only depicts the localization and extent of fibrous plaques in patients with Peyronie's disease but also reveals the presence of inflammation. This makes MR imaging the technique of choice for planning therapy and for evaluating the response to conservative treatment. PMID- 1590120 TI - Nonovarian gynecologic cysts: MR imaging findings. PMID- 1590121 TI - When the solution is the problem: a brief history of the shoe fluoroscope. PMID- 1590122 TI - Intraarticular fractures of the calcaneus: value of CT findings in determining prognosis. AB - The prognosis of intraarticular calcaneal fractures is variable, ranging from severe functional impairment and pain to complete return of normal function. Clinical assessment and CT scanning were performed 1-11 years after fracture in 45 patients (51 fractures) to determine the relationship between the CT findings and clinical status. Conservatively treated (n = 18) and surgically treated (n = 33) fractures were assessed. Clinical assessment included evaluation of subjective parameters (pain, activity, gait, and use of orthotics) and objective measurement of subtalar motion. CT evaluation included assessment of abnormalities in the posterior subtalar joint, loss of calcaneal height, tendon abnormalities, and calcaneocuboid joint abnormalities. A poor clinical outcome, caused by loss of subtalar motion, was more common when CT showed incongruity or degeneration of the posterior facet (p = .04) and when Bohler's angle was decreased (p = .0006). Other CT findings, such as loss of calcaneal height and tendon abnormalities, did not correlate with clinical outcome. An unexpected finding was that surgical screws were intraarticular in eight (24%) of 33 surgically treated patients; however, this finding was not significantly associated with poor clinical outcome. Our findings indicate that the CT findings of degenerative change and incongruity of the posterior subtalar joint correlate significantly with poor clinical outcome. PMID- 1590123 TI - Do metastases in vertebrae begin in the body or the pedicles? Imaging study in 45 patients. AB - We analyzed CT scans of the spine obtained in patients with vertebral metastases to determine what specific portion of the vertebra is initially involved by metastasis. The CT findings were then correlated with the abnormalities seen on plain films. Forty-five patients with histologically proved metastases in 95 vertebrae were included in the study. In all patients, CT scans and plain films of the spine were obtained within 1 week of each other. Analysis of the CT scans showed that the vertebral body was the portion of the vertebra that was most frequently destroyed by the metastases. Destruction of a pedicle was never identified in the absence of involvement of the body. The opposite was true on plain films, in which the most common finding was destruction of the pedicles. CT showed that the position of the metastases in the vertebra correlated with the sites of entry of the vertebral vessels. Our results show that the initial anatomic location of metastases within vertebrae is in the posterior portion of the body. Analysis of CT scans shows that the body is involved before the pedicles, although destruction of the pedicles is the most common finding on plain films. The pedicles are not the primary site of metastatic involvement. Destruction of the pedicles occurs only in combination with involvement of the vertebral body. PMID- 1590124 TI - MR imaging of the shoulder: appearance of the supraspinatus tendon in asymptomatic volunteers. AB - MR imaging has been shown to be accurate in the diagnosis of rotator cuff disruption and tear. Uncertainty remains about the significance of increased signal intensity in the critical zone of the supraspinatus tendon without visible disruption of tendon fibers and about the significance of other secondary findings commonly encountered with rotator cuff abnormalities, such as musculotendinous retraction or obliteration and fluid in the subacromial space. We evaluated proton density-weighted and T2-weighted coronal images (obtained on a 1.5-T superconductive MR imager) of 55 shoulders in 32 asymptomatic volunteers for signal intensity in the supraspinatus tendon, location of the musculotendinous junction, fluid in the subacromial-subdeltoid space, and appearance of the fat plane. In 89% of shoulders, the supraspinatus tendon showed focal, linear, or diffuse increased signal intensity with or without loss of the low-signal-intensity tendon margin on proton density-weighted images. None of these findings were confirmed on T2-weighted images. The musculotendinous junction was always located within an area 15 degrees medial to 30 degrees lateral to the highest point (12 o'clock) on the humeral head convexity. A peribursal fat plane was poorly defined or absent in 49%, and fluid in the subacromial-subdeltoid space was found in 20%. Increased signal intensity in the supraspinatus tendon on proton density-weighted images without a corresponding increase on T2-weighted images, the presence of small amounts of fluid in the subacromial space, and the lack of preservation of the subdeltoid fat plane are common findings in asymptomatic shoulders and by themselves are poor predictors of rotator cuff disease. PMID- 1590125 TI - Aneurysmal bone cyst developing after anterior cruciate ligament tear and repair. PMID- 1590126 TI - MR appearance of intramuscular injections. PMID- 1590127 TI - MR diagnosis of macrodystrophia lipomatosa. PMID- 1590128 TI - Posttraumatic adrenal hemorrhage in children: CT findings in 34 patients. AB - The medical records and CT scans of 34 children with posttraumatic adrenal hemorrhage were reviewed. Adrenal hemorrhage was unilateral in 32 children; most injuries were on the right side. Bilateral hemorrhage was present in two children. The injured gland was oval in 27 cases and triangular in nine. Gland size ranged from 7 to 45 mm long and 4 to 30 mm wide. All adrenal hemorrhages had decreased attenuation relative to liver and spleen on contrast-enhanced CT. Ipsilateral diaphragmatic crural thickening was a frequent (61%) associated finding. Ipsilateral intraabdominal (61%) and intrathoracic (44%) injuries were often present. Clinical signs of adrenocortical insufficiency were not observed in any child. In summary, posttraumatic adrenal hemorrhage is uncommon in children. The hemorrhage is usually unilateral, right sided, and associated with ipsilateral visceral injury. PMID- 1590129 TI - Neonatal intestinal ischemia with bowel perforation: an in utero complication of maternal cocaine abuse. PMID- 1590130 TI - Persistent infantile odontoid process: a variant of abnormal atlantoaxial segmentation. PMID- 1590131 TI - Congenital absence of the left pulmonary artery associated with double-outlet right ventricle. PMID- 1590132 TI - Rathke's cleft cyst. PMID- 1590133 TI - Fast spin-echo MR imaging of the brain and spine: current concepts. PMID- 1590134 TI - Fractures of the nasolacrimal fossa and canal: a CT study of appearance, associated injuries, and significance in 25 patients. AB - The bony nasolacrimal fossa and canal, which protect the more distal excretory portion of the lacrimal apparatus, the nasolacrimal sac and duct, are contained within the medial portion of the orbit and lateral aspect of the nose, sites that are commonly injured in facial trauma. The CT scans of 25 patients who sustained fractures of the nasolacrimal fossa and/or canal as a result of motor vehicle accidents were reviewed to determine the appearance of the fractures and to determine types of facial fractures also present. The patients' clinical records were reviewed to determine the frequency of associated complications. Thirty-six fractures of the nasolacrimal fossa and canal were found in the 25 patients. In 20 patients these were associated with complex fractures of the midportion of the face; the other five patients had simple unilateral facial fractures. Three kinds of nasolacrimal fractures were identified: avulsion of the fossa, comminution of the fossa or canal, and linear fractures of the canal. Of the 19 fractures involving the nasolacrimal fossa, 15 consisted of an avulsed fragment of bone containing the nasolacrimal sac and four had comminution of the nasolacrimal fossa. The majority of the fractures of the nasolacrimal canal (15 patients) were comminuted. Our results show that nasolacrimal fractures occur in association with simple unilateral facial fractures and with more complex fractures of the midface and that the fractures follow certain patterns. Complications related to injury to the nasolacrimal sac and duct were documented in five patients. Although this number is significant, it is fewer than we expected, considering the severity of the injuries. PMID- 1590135 TI - Neurosyphilis in HIV carriers: MR findings in six patients. AB - Neurosyphilis, a sexually transmitted disease that can cause neurologic damage, has become increasingly prevalent in the AIDS era. HIV carriers can contract neurosyphilis without the presence of other concurrent opportunistic infections. Because MR findings of neurosyphilis are seldom reported, we retrospectively reviewed and evaluated contrast-enhanced MR images of six young (average age, 33 years) HIV-positive men with high serum and CSF VDRL titers indicative of neurosyphilis. All six patients tested negative for concurrent opportunistic infections. Five patients had acute or subacute strokelike symptoms involving the basal ganglia or middle cerebral arteries; one had a parietal convexity mass mimicking meningioma with headache and ataxia. Contrast-enhanced MR images showed patchy enhancement involving the basal ganglia and middle cerebral artery territories in the first five patients and the convexity mass in the sixth patient. On the basis of brain biopsy, a convexity mass was diagnosed in the patient with syphilitic gumma. The imaging findings of the remaining five patients represented ischemic infarct caused by meningovascular syphilis. After penicillin treatment, serum and CSF VDRL titers decreased, and neurologic signs and symptoms improved in all six patients. A follow-up MR study in the patient with the gumma showed that the lesion resolved almost completely. In young HIV patients with stroke symptoms or a convexity mass, neurosyphilis should be considered. Contrast-enhanced MR can reveal the extent of involvement by neurosyphilis and should be used to facilitate diagnosis and proper treatment. PMID- 1590136 TI - Rasmussen's encephalitis: neuroimaging findings in four patients. AB - Rasmussen's encephalitis is a devastating disease of childhood causing progressive neurologic deficits and intractable seizure activity. Patients frequently have episodes of epilepsia partialis continua and, much less frequently, generalized status epilepticus. The seizures are intractable despite aggressive medical management. In advanced cases, hemispherectomy appears to be the only option to control the seizures. Permanent physical and mental impairments are inevitable. The cause of this disease is unknown, although pathologic specimens demonstrate nonspecific changes that are compatible with viral encephalitis. The progressive brain damage is typically so insidious in onset and gradual in course that it is difficult to make an accurate diagnosis on the basis of clinical evidence. We retrospectively evaluated the CT, xenon CT, positron emission tomographic, and MR neuroimaging findings in four young patients with pathologically suspected Rasmussen's encephalitis (three patients had CT scans, two had xenon CT scans, two had MR scans, and one had a positron emission tomogram). All studies showed abnormalities of the involved cerebral hemisphere: CT and MR revealed nonspecific atrophy, xenon CT showed decreased cerebral blood flow, and positron emission tomography revealed a hypometabolic state. Rasmussen's encephalitis is a diagnosis of exclusion; however, the information obtained from neuroimaging studies in combination with the clinical course should suggest this disorder. PMID- 1590137 TI - Role of MR imaging in the management of spinal infections. AB - Infection of the spine is a major category of spinal disease that is difficult to differentiate clinically from degenerative disease, noninfective inflammatory lesions, and spinal neoplasm. The infection can affect the vertebrae, intervertebral disks, paraspinal soft tissues, the epidural space, the meninges, and/or the spinal cord. Specific causative organisms include bacteria (pyogenic, granulomatous), fungi, parasites (Echinococcus, Schistosoma), and viruses. Early diagnosis and prompt treatment are essential to prevent permanent neurologic deficit and/or spinal deformity. Imaging plays an important role in the overall evaluation of these lesions, and the ideal technique is expected to provide information that will help characterize and delineate the disease process, guide biopsy and/or drainage procedures, suggest method of treatment (medical vs surgical), and assess response to therapy. The aim of this article is to review the advantages and limitations of MR imaging in the management of spinal infections. PMID- 1590138 TI - Intradural schwannomas of the spine: MR findings with emphasis on contrast enhancement characteristics. AB - Intradural extramedullary schwannomas are nerve sheath neoplasms that consist of focal proliferations of Schwann cells involving a spinal nerve. We reviewed the MR findings in seven patients with pathologically proved intradural schwannomas. The contrast-enhancement characteristics on MR images were determined and compared with the histologic features of the tumor. Six lesions were variably hyperintense on T2-weighted images and one was uniformly hypointense compared with the signal intensity of the spinal cord. Signal on T1-weighted images ranged from hypointense to isointense. All seven tumors showed heterogeneous enhancement; in five, the enhancement involved only the periphery of the lesion. The pattern of enhancement did not correlate with the signal characteristics noted on unenhanced T1- and T2-weighted images. Pathologically, hyaline thickening of vessel walls and cyst formation were prevalent in the peripherally enhancing lesions. However, enhancement did not correlate with the relative proportion of Antoni type A and type B tissue. Recognition of the MR characteristics of intradural extramedullary schwannomas may be helpful in the differential diagnosis of spinal tumors. In particular, peripheral contrast enhancement of an intradural extramedullary tumor on MR images should suggest the diagnosis of schwannoma. PMID- 1590139 TI - Schistosomal granuloma of the spinal cord: evaluation with MR imaging and intraoperative sonography. PMID- 1590140 TI - Chest case of the day. Pulmonary edema associated with tocolytic therapy. PMID- 1590141 TI - Chest case of the day. Obstruction of the left brachiocephalic vein. PMID- 1590142 TI - Chest case of the day. Respiratory tract papillomatosis. PMID- 1590143 TI - Chest case of the day. Acute silicosis. PMID- 1590144 TI - Abdominal case of the day. Superior mesenteric venous thrombosis. PMID- 1590145 TI - Abdominal case of the day. Complicated appendicitis. PMID- 1590146 TI - Abdominal case of the day. Gastric adenocarcinoma. PMID- 1590147 TI - Abdominal case of the day. Interruption of the inferior vena cava with azygos continuation. PMID- 1590148 TI - Skeletal case of the day. Parosteal osteosarcoma. PMID- 1590149 TI - Skeletal case of the day. Radiation-induced osteochondroma. PMID- 1590150 TI - Skeletal case of the day. Brown tumor. PMID- 1590151 TI - Skeletal case of the day. Synovial osteochondromatosis. PMID- 1590152 TI - Pediatric case of the day. Aneurysmal bone cyst. PMID- 1590153 TI - Pediatric case of the day. Fibromuscular dysplasia (intimal fibroplasia) with aneurysm. PMID- 1590154 TI - Pediatric case of the day. Non-Hodgkin's lymphoma in the pancreas. PMID- 1590155 TI - Pediatric case of the day. Giant posterior mediastinal cystic hygroma. PMID- 1590156 TI - Neuroradiology case of the day. Progressive multifocal leukoencephalopathy. PMID- 1590157 TI - Neuroradiology case of the day. Ectopic posterior lobe of pituitary gland associated with panhypopituitarism. PMID- 1590158 TI - Neuroradiology case of the day. "Cryptic" arteriovenous malformations. PMID- 1590159 TI - Neuroradiology case of the day. Meningitis caused by Neisseria meningitidis. PMID- 1590160 TI - Nuclear medicine case of the day. Miliary tuberculosis. PMID- 1590161 TI - Nuclear medicine case of the day. Fibrous dysplasia in a patient with neurofibromatosis. PMID- 1590162 TI - Nuclear medicine case of the day. Hereditary multiple exostoses. PMID- 1590163 TI - The information perspective of radiology. PMID- 1590164 TI - Thoracic imaging, 1992. PMID- 1590165 TI - Adverse reaction to contrast material in a patient treated with local interleukin 2. PMID- 1590166 TI - A useful sign for distinguishing clustered skin calcifications from calcifications within the breast on mammograms. PMID- 1590167 TI - Motion artifact simulating aortic dissection. PMID- 1590168 TI - A giant Meckel's diverticulum in an adult. PMID- 1590169 TI - Retroperitoneal fibrosis. PMID- 1590170 TI - Hemoperitoneum due to traumatic avulsion of a pedunculated uterine leiomyoma. PMID- 1590171 TI - Hysterosalpingography in England. PMID- 1590172 TI - Retrieval of a coil embolus: the enemy of good is better. PMID- 1590173 TI - Indications for radiography in acute ankle injuries. PMID- 1590174 TI - Hemisection of the cervical spinal cord caused by a stab wound: MR findings. PMID- 1590175 TI - Multiple meningiomas. PMID- 1590176 TI - MR of the base of the pons in Wilson disease. AB - The authors describe unusual MR findings in three patients with Wilson disease, eg, white matter changes in the base of the pons, and speculate whether the changes are caused by Wilson disease or by concomitant disease, and whether the pontine lesions they observed are primary or related to lesions located more rostrally. PMID- 1590177 TI - The challenge of carotid occlusion. PMID- 1590178 TI - The ultimate recognition for neuroradiology. PMID- 1590180 TI - Neuroradiology and neuropsychiatry: a new alliance. PMID- 1590179 TI - Abnormalities of the septum pellucidum on MR scans in first-episode schizophrenic patients. AB - PURPOSE AND METHODS: Cavities in the septum pellucidum have been widely regarded in clinical neurology or in autopsy series as incidental findings of little clinical importance; however, an association between this developmental anomaly and a diagnosis of psychosis has been reported. We compared MR brain scans of schizophrenic patients with normal control subjects to determine the prevalence of this finding in the two groups: RESULTS: A cavum septum pellucidum was found in 14 of 62 (23%) schizophrenic patients and only one of 46 control subjects (2%). Pronounced enlargement of the cavum septum and a cavum vergae were seen only in two schizophrenic subjects. A partial agenesis of the corpus callosum was also seen in one of the schizophrenic cases with the largest cavum septum pellucidum. CONCLUSIONS: The increased prevalence of a cavum septum pellucidum, the cavum vergae, and partial callosal agenesis in schizophrenics support the hypothesis that anomalous development of the brain is an important aspect of this disorder. The disturbed structures are closely linked developmentally to the limbic system which has been implicated etiologically in studies of schizophrenia. PMID- 1590181 TI - Effective dose equivalents to patients undergoing cerebral angiography. AB - PURPOSE: To determine values of the effective dose equivalent, HE, for patients undergoing diagnostic cerebral angiography and compare these values with radiation doses received by patients undergoing other diagnostic examinations of the head. METHODS: The radiographic techniques for ten patients undergoing cerebral angiography were recorded and used to obtain the product of the entrance skin dose and the x-ray beam cross-sectional area. These measured dose-area product data were converted into effective dose equivalents employing published conversion factors which take into account the part of the patient anatomy irradiated and the radiographic technique factors employed. RESULTS: The average patient HE value was 10.6 mSv, with a range of 2.7-23.4 mSv. Fluoroscopy contributed approximately 67% of the total HE, with cut films and digital subtraction angiography contributing 26% and 7%, respectively. CONCLUSIONS: The radiation doses (HE) to patients undergoing diagnostic cerebral angiography are comparable to the patient doses in nuclear medicine brain studies where the typical HE is approximately 10 mSv. In CT, the patient dose is approximately 2 mSv, whereas in plain skull x-ray examinations, the patient dose is much lower at approximately 0.15 mSv. PMID- 1590182 TI - New risks, new doses. PMID- 1590183 TI - Nonoperative management of acute epidural hematoma diagnosed by CT: the neuroradiologist's role. AB - PURPOSE: To determine whether certain patients with epidural hematomas would benefit from conservative treatment and to assess the neuroradiologist's role in decision-making. METHODS: We reviewed the CT scan findings, clinical presentation and outcome of 48 consecutive patients with epidural hematoma managed at our institution within the past 5 years. In 18 patients, initial management was nonsurgical, and only one of these went on to require surgery due to clinical deterioration and evidence of enlargement of hematoma on CT. The remainder of these 18 did well without surgery. OBSERVATIONS AND CONCLUSIONS: Clinical indicators of neurologic dysfunction (decrease in Glasgow coma scale score, pupillary dilatation, and hemiparesis) in the presence of even small epidural hematomas usually dictates the need for surgical management. The role of the neuroradiologist is most important when the patient presents in a good clinical state, when identification of both favorable and unfavorable prognostic factors on Ct is essential. The initial diameter of nonsurgically managed epidural hematomas generally must be small (mean, 1.26 cm in our series, all under 1.5 cm), and midline shift should be minimal (mean, 1.8 mm in our series). The identification of lucent areas within the epidural hematoma (suggesting active bleeding), or CT evidence of uncal herniation, can be ominous and the neurosurgeon must be alerted to their presence. Even in the presence of a favorable clinical status, presence of a larger epidural hematoma with significant mass effect or central lucent areas should alert the neuroradiologist and neurosurgeon to the strong possibility of sudden neurologic deterioration, and indicate the probable need for surgical management. PMID- 1590184 TI - Radiologic-pathologic correlation. Epidermoid tumor of the cerebellopontine angle. AB - This case demonstrated the classic gross pathologic, CT, and MR appearances of epidermoid tumors. The imaging features and differential diagnosis are summarized. PMID- 1590185 TI - The early history of neuroradiology at the Medical School of the University of Minnesota, 1937-1939. PMID- 1590186 TI - Fat-suppression failure artifacts simulating pathology on frequency-selective fat suppression MR images of the head and neck. AB - PURPOSE: To describe fat-suppression failure artifacts and to caution against their misinterpretation. METHOD: Magnetic-susceptibility artifacts were studied in a phantom model and the results were compared to MR images obtained in clinical cases. FINDINGS: Artifacts manifested themselves as regions of focal fat suppression failure and appeared as bright signals without geometric distortions at magnetic-susceptibility interfaces along the static field (z) direction. The location and extent of these artifacts were independent of either frequency or phase-encoding direction and are different from those observed in gradient-echo images. CONCLUSIONS: In representative clinical MR exams, these artifacts were identified in the high nasopharynx and low orbit and should not be misinterpreted as pathology. PMID- 1590187 TI - Facial trauma and 3-D reconstructive imaging: insufficiencies and correctives. AB - PURPOSE: To address the clinical relevance of and optimal technique for 3-D CT imaging of facial trauma. METHODS: Bioengineered cadaveric models were developed to enhance the concepts of LeFort. Diverse CT imaging techniques were applied to obtain optimal data sets for processing on various 3-D workstations. The fidelity of the 3-D reconstructions was determined by comparison with photographs of the cadaveric models. Optimized 3-D images were then used in conjunction with the initial 2-D data sets to assess whether additional accuracy was contributed by the 3-D images in the evaluation of modeled facial fractures. RESULTS: Image definition was heavily dependent upon the specific 3-D reconstruction algorithm and the processor utilized. Orbital fractures were best imaged when 1- to 1.5-mm coronal sections were processed on an advanced 3-D workstation. The 3-D CT images resulted in additional accuracy in the 2-D CT evaluation of facial fractures in 29% of trials. CONCLUSIONS: We believe that bioengineered models of facial trauma -matched with appropriate CT scanning parameters--facilitate graphically reliable 3-D reconstructive imaging. 3-D reconstructions can improve accuracy in the 2-D CT evaluation of facial trauma. PMID- 1590188 TI - 3-D reconstruction for evaluation of facial trauma. PMID- 1590189 TI - Frontal sinus fractures: evaluation of CT scans in 132 patients. AB - PURPOSE: To determine the frequency of detection of frontal sinus fractures on initial CT scans of patients with intracranial injuries, and to characterize associated injuries. METHODS: The initial head CT scans in 132 patients with clinical or radiographic evidence of a frontal sinus fracture were retrospectively reviewed to further characterize the fracture. Additional radiographic studies and medical records were reviewed to determine associated injuries, therapy, clinical outcome, and complications. RESULTS: In 90% (124) of the patients, the frontal sinus fractures were visualized on initial head CT scans that were obtained to evaluate suspected intracranial injury. Complex fractures involving both the anterior and posterior wall of the sinus accounted for 65% of cases (86 patients), whereas fractures of the anterior wall only or posterior wall only occurred in 24% (32) and 11% (14) of patients, respectively. Significant intracranial hemorrhage occurred in over 90% of patients with fractures involving the posterior wall. CONCLUSIONS: In general, fractures that involved the posterior wall had more complications and a worse clinical outcome than fractures that only involved the anterior wall; nearly all frontal sinus fractures can be detected on head CT studies in patients with intracranial injuries. PMID- 1590190 TI - Recurring patterns of inflammatory sinonasal disease demonstrated on screening sinus CT. AB - PURPOSE: In order to define specific features on screening sinus CT (SSCT) that will aid the endoscopic surgeon in his approach to patients with inflammatory sinonasal disease, we sought to answer four questions: 1) what recurring patterns of inflammatory sinonasal disease are evident on SSCT; 2) what is the relative frequency of these recurring patterns; 3) how do these CT patterns correlate with the known sinus mucociliary drainage routes; and 4) what are the characteristic radiologic features of each pattern? METHODS: We reviewed the clinical and radiologic records of 500 consecutive patients who underwent SSCT as a prelude to possible functional endoscopic sinus surgery. RESULTS: Five recurring radiologic patterns of sinonasal inflammatory disease were identified: 1) infundibular (129/500 or 26%), 2) ostiomeatal unit (126/500 or 25%) 3) sphenoethmoidal recess (32/500 or 6%), 4) sinonasal polyposis (49/500 or 10%), and 5) sporadic (unclassifiable) (121/500 or 24%) patterns. Normal SSCT was seen in 133/500 patients (27%). CONCLUSION: Identification of specific patterns of sinonasal disease permits grouping of patients into nonsurgical (normal CT), routine (infundibular, ostiomeatal unit, and most sporadic patterns) and complex (sinonasal polyposis and sphenoethmoidal recess patterns) surgical groups. Assignment of patients to radiologic patterns allows a tailored surgical approach. PMID- 1590191 TI - Aneurysms of spinal arteries associated with intramedullary arteriovenous malformations. I. Angiographic and clinical aspects. AB - PURPOSE: To evaluate the nature of aneurysms of the spinal arteries, their relative frequency, and the risks associated with these lesions. METHODS: We retrospectively reviewed the spinal angiographic studies of 186 patients with spinal cord vascular malformations--70 intramedullary AVMs, 44 extra (peri) medullary AV fistulas, and 72 dural AV fistulas. RESULTS: Fifteen spinal artery aneurysms (SAs) in 14 out of 70 patients (20%) with an intramedullary AVM were discovered. No SAs were observed in the other types of spinal vascular malformations. The intramedullary AVMs with SAs were cervical in seven cases and thoracic in the other seven cases (one of the thoracic had two SAs). Fourteen SAs were located on a major feeding vessel to the associated intramedullary AVM (10 on the anterior spinal artery and four on a posterior spinal artery and only one SA was located remote from the AVM feeding vessels. This remote aneurysm was located on the intercostal artery feeding a vertebral angioma in a patient with metameric angiomatosis. Subarachnoid hemorrhage occurred in all cases of SA. The presence of a SA carried a statistically significant (P less than .05) increase in the risk of bleeding. CONCLUSIONS: Although increased blood flow seems to be an important factor in formation of these SAs associated with intramedullary AVMs, the role of a developmental vascular anomaly must be stressed: metameric angiomatosis was found in six out of the 14 patients (43%). PMID- 1590192 TI - Aneurysms of spinal arteries associated with intramedullary arteriovenous malformations. II. Results of AVM endovascular treatment and hemodynamic considerations. AB - PURPOSE: To evaluate the changes occurring in spinal aneurysm (SA) size related to modification of endovascularly treated AVMs. METHODS: Fourteen patients with an intramedullary AVM and associated SA underwent endovascular treatment of their AVM with particles. Embolization sessions numbered from one to 14 (mean five) in each patient. RESULTS: Four patients had SAs with size changes mirroring those of the AVM with embolization: these decreased in size or disappeared after AVM reduction or cure and increased or recurred after AVM recanalization. A second group of patients had SAs that remained unchanged despite AVM changes (six of seven of these were in patients with metameric angiomatosis). CONCLUSIONS: Results in the first group lend support to the hemodynamic theory of associated aneurysm formation. On the other hand, aneurysms that remained unchanged probably are not AVM flow-related and could be an expression of an extensive vascular disorder such as metameric angiomatosis; however, hemodynamic and developmental factors could be concurrent. PMID- 1590193 TI - Embolization of spinal dural arteriovenous fistula with polyvinyl alcohol particles: experience in 14 patients. AB - PURPOSE: To assess the effectiveness, initial and long term, of embolization using polyvinyl alcohol particles (PVA) particles in patients with spinal dural arteriovenous fistulas (SDAVF). METHODS: The initial treatment in 14 patients with SDAVF was embolization with PVA particles. Postembolization occlusion of the SDAVF was documented angiographically in all cases. RESULTS: All 14 patients initially showed an improvement in clinical symptoms, but the neurologic status of 11 patients subsequently deteriorated. Of the 11 patients who had recurrence of symptoms, nine had angiographically proven recurrences of their SDAVF while two had negative follow-up of spinal angiography. PVA embolization is ineffective for the treatment of SDAVF and is not without risk. CONCLUSION: On the basis of a literature review of the other two alternative treatments (operation or liquid adhesive embolization) available for SDAVF and our preliminary experience with N butyl cyanoacylate (NBCA) embolization, we suggest that NBCA embolization be the initial treatment of choice for SDAVF; if that procedure is not possible, or is unsuccessful, then operation is recommended. PMID- 1590194 TI - Spinal dural arteriovenous fistula: the role of PVA embolization. PMID- 1590195 TI - Hippocampal and limbic terminology. PMID- 1590196 TI - Angiographic complications during stereotactic radiosurgery for cerebral arteriovenous malformations. PMID- 1590198 TI - MR and CT evaluation of profound neonatal and infantile asphyxia. AB - PURPOSE: To determine the CT and MR characteristics of the brains of infants who have suffered profound asphyxia and correlate those characteristics with pathophysiologic processes. METHODS: MR and CT scans of 16 patients who suffered profound hypoxic-ischemic injury in the perinatal (12 patients) and postnatal (4 patients) periods were retrospectively reviewed in a search for characteristic imaging features. RESULTS: Injury in the perinatal period: subacute MR showed short T1 and T2 in the ventral lateral thalami, posterolateral lentiform nuclei, posterior mesencephali, and hippocampi; MR 1 to 16 years after injury showed atrophy or T2 prolongation in the aforementioned regions, the lateral geniculate nuclei and perirolandic cerebral cortex. Asphyxia later in infancy: subacute MR showed T2 prolongation in the corpus striatum and most of the cerebral cortex (perirolandic sparing); MR weeks to months later showed atrophy of the aforementioned areas, the lateral geniculate nuclei and hippocampi. Acute CT in both groups showed basal ganglia hypodensity. CONCLUSIONS: The injury patterns observed in neonates and infants with profound hypoxic-ischemic injury vary with the age of the patient at the time of the injury. The change in pattern of damage is suggested to be the result of structural and physiologic changes in the maturing brain. The patterns appear to be consistent and are well demonstrated by MR. PMID- 1590197 TI - CT and MR evaluation of intracranial involvement in pediatric HIV infection: a clinical-imaging correlation. AB - PURPOSE: To review the cranial CT and MR examinations of 29 children with perinatally transmitted HIV infection and correlate the imaging findings with clinical and pathologic data. METHODS: 28 children were examined with CT, four with MR. RESULTS: CT abnormalities were seen in 25 children studied (89%), including cerebral atrophy (25 children), basal ganglia calcification (10 children), periventricular frontal white matter calcification (four children), cerebellar calcification (one child), white matter low attenuation areas (two children), intracranial hemorrhage (three children) and cerebral infarction (one child). Intracranial calcifications were only seen in association with cerebral atrophy and were never seen prior to 1 year of age. Calcifications in the periventricular white matter or cerebellum were always associated with basal ganglia calcifications. MR abnormalities were seen in all four children studied; cerebral atrophy (four children), areas of high signal intensity in white matter (four children), loss of normal posterior pituitary high signal intensity (one child). Cerebral atrophy appeared to be a nonspecific finding that was seen in some children in the absence of neurologic signs and symptoms. All children with intracranial calcifications had developmental delay. Intracranial hemorrhage was seen in children with severe thrombocytopenia. Focal intracranial infections were unusual and neoplastic lesions were not found. CONCLUSIONS: Cerebral atrophy, basal ganglia calcifications, and focal white matter lesions were the most common abnormalities seen neuroradiologically in our series of HIV-infected children; cerebral atrophy was a nonspecific finding. PMID- 1590199 TI - Bruton-type (congenital X-linked) agammaglobulinemia: MR imaging of unusual intracranial complications. AB - The authors describe two patients with Bruton-type agammaglobulinemia, their purpose being to indicate the spectrum of findings, clinical and imaging. MR in one patient revealed diffuse leptomeningeal enhancement in the brain and spine; in the second patient, a heterogeneous mass was seen that had broken through the basiocciput and displaced a cerebellar hemisphere. Awareness of the common and unusual CNS manifestations of this disease can impact clinical management. PMID- 1590200 TI - Synovial cyst of the high cervical spine causing myelopathy. AB - The authors describe the myelographic and postmyelographic CT findings of an extradural mass with cord compression in an 82-year-old woman. Synovial cysts generally occur posterolaterally and are associated with degenerative facet joints; an unusual site together with facet joint disease should alert the observer to the possibility of a synovial cyst. PMID- 1590201 TI - Enhancement of gray matter in anterior spinal infarction. PMID- 1590202 TI - Intramedullary spinal cord tuberculoma in a patient with AIDS. AB - Intramedullary spinal cord tuberculoma in a young, homosexual man with AIDS was detected with the use of MR and confirmed pathologically. MR findings were similar to those seen in other intramedullary lesions, eg, astrocytoma, ependymoma, hemangioblastoma, metastasis, lymphoma, and opportunistic infections. Delineation of the lesion improved with administration of Gd-DTPA; enhancement of the lesion, however, does not always correlate with true tumor margins at pathologic examination. PMID- 1590203 TI - Assessment of carotid artery stenosis by MR angiography: comparison with x-ray angiography and color-coded Doppler ultrasound. AB - PURPOSE: To compare magnetic resonance angiography (MRA) with duplex Doppler ultrasound (US) and x-ray angiography (XRA) in the evaluation of the carotid bifurcation. METHODS: The carotid arteries of 61 patients were studied using MRA, US, or XRA; 31 of the patients underwent all three examinations. MRA included both 2D and 3D time-of-flight sequences. Internal and external carotid artery origins were graded normal, mild, moderate, severe, or critical stenosis, or complete occlusion by each of the three studies. RESULTS: Spearman rank correlations of both internal and external carotid artery grades were 0.85 (MRA and XRA), 0.69 (MRA and US), and 0.73 (XRA and US). For internal carotid artery origins only, the correlations were 0.94 (MRA and XRA), 0.85 (MRA and US), and 0.82 (XRA and US). Of discrepancies in internal carotid artery interpretation greater than one grade, seven resulted from US error, three from MRA error, and one from XRA error. A 2-cm partially thrombosed aneurysm detected by US and MRA was missed by XRA. Of 16 possible ulcers on XRA, 11 were noted by MRA, none by US. CONCLUSIONS: MRA and XRA are similar in assessment of carotid bifurcation stenosis. MRA, like US, permits direct visualization of plaque. This preliminary study suggests that MRA may be used to clarify equivocal findings of US, or replace XRA in presurgical planning. PMID- 1590205 TI - Protection against viruses. PMID- 1590204 TI - Dispensing the wrong medication. PMID- 1590206 TI - Diabetes: recognizing symptoms, preventing complications. PMID- 1590207 TI - Pharmacy promotion of tobacco use among children in Massachusetts. AB - The role played by pharmacies in the promotion and distribution of tobacco to children was assessed in a survey of 100 pharmacies. Of the 100 surveyed, 95 sold tobacco products, 50 advertised tobacco, 42 advertised the cigarette brands that are most appealing to children, and 23 displayed the Camel cartoon advertisements that have been identified as being targeted specifically at children. Candy tobacco products were sold in 22% of the pharmacies. Of the pharmacies selling tobacco, 81% were willing to sell it to minors illegally. The five pharmacies that did not carry tobacco products were independent stores. When compared to chain pharmacies, independent pharmacies more frequently advertised tobacco (p less than 0.05) but were not more likely to sell it to children. The authors contend that pharmacists who sell tobacco violate the profession's Code of Ethics and play an important role in the promotion of tobacco use among children. PMID- 1590208 TI - Pharmacists who choose not to sell tobacco. PMID- 1590209 TI - Reimbursement for cognitive services: Quebec's experience. PMID- 1590210 TI - DPS--the PMA perspective. PMID- 1590211 TI - Developing a competitive business. PMID- 1590212 TI - Smoking cessation: treatment options and the pharmacist's role. PMID- 1590213 TI - Good science or good business? PMID- 1590214 TI - Occupational noise exposures and hearing loss in fire fighters assigned to airport fire stations. PMID- 1590215 TI - Consultants listing-January 1992. PMID- 1590216 TI - Immunochemical quantification and particle size distribution of airborne papain in a meat portioning facility. AB - The use of enzymes in industry continues to expand. With this increased use comes a concerted need to better understand potential respiratory health hazards to exposed workers and to quantify exposure levels that cause impaired health. To this end, projects were undertaken by the National Institute for Occupational Safety and Health (NIOSH) Health Hazard Evaluations Program and Cole Associates whereby this information was collected. Data concerning medical evaluation and aspects of industrial hygiene are the subjects of two separate reports from these respective groups. This method/results report includes a description of (1) a sensitive immunoradiometric assay for the quantification of airborne papain and its particle size distribution, (2) measurement of papain from both general area and personal breathing zone air samples obtained from a meat processing plant that used this immunochemical analysis, (3) a sampling strategy, and (4) an improved air sample processing technique. Airborne papain was measured at levels ranging from low nanogram to microgram per cubic meter concentrations. Approximately half of the papain activity was associated with particles having an aerodynamic diameter of less than 9.4 microns. These data point to a need for containment and controls in the manufacture and use of such compounds. This approach can be considered by the hygienist as an effective tool to be used in conjunction with epidemiologic studies to help set standards that are practical, safe, and maintained. PMID- 1590217 TI - Measurement of 3-D facial contours for the design of half-face respirators. AB - A portable anthropometric test rig capable of obtaining three-dimensional face shape data was developed and used to obtain information relating to facial shape, stiffness, and variance for a selected subgroup of respirator users in the Australian work force. A respirator seal shape most suited to the sample population was obtained by studying the central portion of the face of all the subjects. The optimum seal shape was established by following the path of minimum variance among all the faces; the method provided information on the shape, dimensions, and stiffness of the optimum seal for a respirator suited to the sample population. The seal surface flexibility required for a comfortable fit was determined by measuring the deflection of the skin caused by an applied pressure and using this information along with face shape variance data. Results indicated that the required flexibility in the seal surface increased toward the lower portion of the face. PMID- 1590218 TI - Characterization of the fiber diameter distributions of synthetic mineral fiber products and their dusts. AB - Procedures to measure the fiber diameter distributions of bulk synthetic mineral fiber products in order to characterize product differences and the diameters of airborne fibers emitted from them have been investigated. Bulk fibers were prepared for size measurement by two methods--one that gently teased fibers apart and another that lightly ground them in a liquid slurry. Bulk products exhibited different contents of respirable fibers, but these were significantly greater when products were prepared by grinding rather than teasing. This was established to result from preferential breakdown of finer fibers into shorter lengths with the former method. Airborne fibers emitted during work operations with products had diameter distributions similar to those of ground fibers, indicating that similar breakdown of finer fibers into shorter lengths occurs for dusts emitted during such operations. PMID- 1590219 TI - A rationale and framework for establishing the quality of human exposure assessments. AB - Exposure assessments, performed as input to an evaluation of potential human health risk, are an element of risk assessment. Risk assessment results feed governmental and corporate risk management decisions, which seek to balance the estimated potential human health risks with other factors. Risk managers presume that the risk information provided to them is scientifically valid and accurate. Government agencies have begun to apply a system known as good laboratory practices (GLP) to ensure adequate data quality on animal studies, which are often the first step in the health-effects evaluation of risk assessment. This paper explores a rationale and framework for establishing the quality of human exposure assessments and proposes a set of good exposure assessment practices (GEAP). The components of the proposed GEAP include the writing of a study protocol before conducting the study, consideration of available resources, specification of an exposure model, a study design (including sampling and analytical methods and data analysis), quality assurance, archiving, communications, and a statement of overall uncertainty in exposure estimates. The GEAP concept is offered as a starting point for developing a consensus among the community of exposure assessors regarding a minimum standard for good practices. If a consensus on GEAP can be reached and applied, exposure assessments would have improved scientific bases, interpretability, and utility. PMID- 1590220 TI - Field evaluation of a sampling and analytical method for environmental levels of airborne hexavalent chromium. AB - Hexavalent chromium, Cr(VI), has been classified as a human respiratory carcinogen. Airborne Cr(VI) emissions are associated with a number of industrial sources including metal plating, tanning, chromite ore processing, and spray painting operations; combustion sources such as automobiles and incinerators; and fugitive dusts from contaminated soil. There has been considerable interest within industry and the regulatory community to assess the potential cancer risks of workers exposed to Cr(VI) at levels substantially below the threshold limit value (TLV) of 50 micrograms/m3. To date, only the workplace sampling and analytical method (National Institute for Occupational Safety and Health [NIOSH] Method 7600) has been validated for measuring airborne Cr(VI), and it can accurately measure concentrations only as low as 500 ng/m3. This paper describes the field evaluation of a sampling and analytical method for the quantitation of airborne Cr(VI) at concentrations 5000 times lower than the current standard method (as low as 0.1 ng/m3). The collection method uses three 500-mL Greenberg Smith impingers in series, operated at 15 Lpm for 24 hr. All three impingers are filled with 200 mL of a slightly alkaline (pH approximately 8) sodium bicarbonate buffer solution. The results of validation tests showed that both Cr(VI) and trivalent chromium, Cr(III), were stable in the collection medium and that samples may be stored for up to 100 days without appreciable loss of Cr(VI). Method precision based on the pooled coefficient of variation for replicate samples was 10.4%, and method accuracy based on the mean percent recovery of spiked samples was 94%. Both the precision and accuracy of the impinger method were within NIOSH criteria. This method could be used to measure ambient concentrations of Cr(VI) in the workplace caused by fugitive emissions from manufacturing processes or chromium-contaminated soils at workplace concentrations well below the current TLV (50 micrograms/m3) or permissible exposure limit (100 micrograms/m3). PMID- 1590221 TI - Deposition patterns of cigarette smoke in human airways. AB - Experimental deposition patterns of cigarette smoke in surrogate human airway systems are very heterogeneous. Particle deposits are enhanced at predictable, well-defined morphological regions; most specifically, carinal ridges within bifurcation zones and along posterior sections of tubular airways. The efficiency of the mucociliary transport mechanism in vivo is also reduced at airway branchings. The geometrical sites of preferential particle deposition and impaired clearance can be correlated with clinically observed anatomical sites exhibiting increased incidences of bronchogenic carcinomas. These locations are not compatible with current theoretical models simulating only the usual particle deposition processes of inertial impaction, sedimentation, and diffusion, while intending to account for particle hygroscopicity. Moreover, data from human subject exposures indicate that heretofore unknown factors affect the distribution of inhaled cigarette smoke. Herein, a new mathematical model is presented that explains cigarette smoke deposition patterns, including bifurcation "hot spots," in terms of composition and cumulative density. The behavior of mainstream cigarette smoke can be related to physicochemical parameters of its particulate and vapor-gas phases and is a result of two distinct effects: (1) particle cloud motion and (2) vapor-gas behavior. In lung airways, Effect 1 is the most prominent. The high particle number,ns approximately equal to 3 x 10(9) cm-3, and mass,rho s approximately equal to 10( 4) g cm-3, concentrations of smoke dictate that a bolus of it has kinetic properties of an entity (Effect 1 above), independent of the aerodynamic size characteristics of individual constituent particles. This motion may be exacerbated by the bulk movement (Effect 2 above) of the vapor-gas phase density of smoke. PMID- 1590222 TI - Frequency and outcome of chest pain after two new coronary interventions (atherectomy and stenting). AB - Between June 1988 and July 1991, 464 new device interventions (Palmaz-Schatz stent or Simpson directional atherectomy) were performed in 410 patients. Chest pain occurred within 72 hours after the procedure in 94 patients (23%). All patients were evaluated with electrocardiograms and cardiac isoenzymes on the day after the procedure, and urgent repeat coronary angiography was performed in 29 chest pain patients (31%). Whereas all 14 patients with abnormal findings on repeat angiography had electrocardiographic changes, 6 of the 20 restudied patients (30%) with electrocardiographic changes had no angiographic explanation for chest pain. Non-Q-wave myocardial infarction occurred in 22 patients (5%) (10 of 35 [29%] with chest pain and electrocardiographic changes, 3 of 44 [7%] with chest pain and no electrocardiographic change, and 9 of 316 [3%] without chest pain). Factors associated with chest pain after new device intervention included a decreased residual percent stenosis (p = 0.05), incomplete revascularization (p = 0.005) and the presence of multivessel disease (p = 0.001). Vessel dissection after stenting but not atherectomy was associated with postprocedure chest pain. Chest pain is common (23%) after new device intervention. Electrocardiographic changes are a sensitive marker of angiographic abnormality and confer a higher risk of non-Q-wave myocardial infarction, but no increase of in-hospital mortality. Determinants of postprocedure chest pain are lower residual percent stenosis, incomplete revascularization and the presence of multivessel disease. Patients with chest pain but no electrocardiographic changes early after successful stent placement or atherectomy need not routinely undergo urgent recatheterization. PMID- 1590223 TI - A patency-oriented strategy for early management of acute myocardial infarction using emergency coronary angiography and selective coronary angioplasty. AB - From June 1988 to March 1991, an unselected cohort of 150 consecutive patients with acute myocardial infarction (AMI) (less than 6 hours) was managed according to a strategy designed to ensure early patency of the infarct-related artery in the maximum number of patients. The following procedures were used: (1) intravenous thrombolysis, which was the usual treatment (n = 103), followed in 98 cases by emergency coronary angiography 90 minutes after the beginning of thrombolysis. This identified 31 thrombolysis failures (32%) and led to 19 rescue angioplasties (18 successes). All patients were then scheduled for predischarge angiography. (2) Direct angioplasty, which was performed in 40 patients because of contraindications to thrombolysis (n = 23), cardiogenic shock (n = 3), diagnostic doubt (n = 7) or "ideal" conditions for direct angioplasty (n = 7). Success (defined as Thrombolysis in Myocardial Infarction [TIMI] flow greater than 1, with a residual stenosis less than 50% in the infarct-related artery) was achieved in 36 of 40 patients (90%). (3) The 7 remaining patients were given conventional medical treatment because of advanced age, contraindications to thrombolysis and angioplasty, or spontaneous reperfusion (confirmed by emergency angiography). In all, emergency angioplasty was performed in the acute phase in 39% of the 150 patients in this nonselected cohort.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590224 TI - Safety of combined intravenous beta-adrenergic blockade (atenolol or metoprolol) and thrombolytic therapy in acute myocardial infarction. AB - One hundred thirty-one patients presenting with acute myocardial infarction (AMI) a mean of 3 hours after the onset of symptoms were treated with oral aspirin and intravenous thrombolytic therapy followed by heparin. One hundred eleven patients (85%) also received intravenous followed by oral beta blockers. Twenty-one patients (19%) discontinued the beta blocker because of complications. Five (4.5%) required the addition of diuretic drugs or converting enzyme inhibitors. Six patients (5%) discontinued the beta blocker after complete mechanical revascularization, and 1 patient was noncompliant. Long-term treatment continued in 90 patients (69%) over a 2-year follow-up period (average 13 months). There were 3 infarct extensions and 3 reinfarctions (5%). Overall mortality at 2 years was 10%. Intravenous beta blockers are well tolerated in most patients treated with thrombolytic agents, aspirin and heparin. They may further improve the survival benefit of chronic beta blocker therapy in the period after AMI. PMID- 1590225 TI - Effectiveness and safety of a single intravenous bolus injection of tissue-type plasminogen activator in acute myocardial infarction. Bolus Dose-Escalation Study of Tissue-Type Plasminogen Activator (BEST) Investigators. AB - The efficacy of multiple intravenous bolus injections of tissue-type plasminogen activator (t-PA) in inducing rapid coronary recanalization in patients with acute myocardial infarction was previously demonstrated. In this Bolus Dose-Escalation Study of Tissue-Type Plasminogen Activator (BEST), the efficacy of 3 different doses of a single rapid intravenous bolus injection of t-PA (dute-plase, Wellcome Foundation, London) in inducing coronary patency (Thrombolysis In Myocardial Infarction perfusion grade 2 or 3) in 64 patients with acute myocardial infarction presenting less than 6 hours after onset of symptoms was investigated. At 60 minutes after administration of t-PA, the infarct-related coronary artery was patent in 9 of 17 patients (53%; 95% confidence interval [CI] 28 to 77%) after 0.3 MU/kg, in 14 of 23 (61%; 95% CI 39 to 80%) after 0.45 MU/kg and in 10 of 14 (71%; 95% CI 42 to 92%) after 0.6 MU/kg. At 90 minutes after t-PA, coronary patency was present in 9 of 17 cases (53%; 95% CI 28 to 77%) after 0.3 MU/kg, in 12 of 24 (50%; 95% CI 29 to 71%) after 0.45 MU/kg and in 10 of 13 (77%; 95% CI 46 to 95%) after 0.6 MU/kg. One patient in each dose group had a silent reoccluded infarct-related artery by 24 hours, and there were 2 clinical reinfarctions before discharge. No major bleeding events were observed. There were 5 hospital deaths, all unrelated to t-PA. A single intravenous bolus injection of 0.6 MU/kg of t-PA appears to be effective in inducing rapid coronary patency and to be safe in patients with acute myocardial infarction. PMID- 1590226 TI - Beneficial effect of amiodarone on cardiac mortality in patients with asymptomatic complex ventricular arrhythmias after acute myocardial infarction and preserved but not impaired left ventricular function. AB - To determine whether the beneficial effect of low-dose amiodarone on survival in patients with complex ventricular arrhythmias after myocardial infarction was dependent on left ventricular (LV) function, results of the Basel Antiarrhythmic Study of Infarct Survival were analyzed. Two hundred twelve patients after acute myocardial infarction with asymptomatic complex arrhythmias were randomly assigned to receive amiodarone 200 mg/day or to a control group and followed up for 1 year. Results of mortality and arrhythmic events were related to baseline radionuclide LV ejection fraction. With preserved (greater than or equal to 40%) LV ejection fraction, there was a significantly lower 1-year cardiac mortality in patients treated with amiodarone (1 of 68 or 1.5%) versus control subjects (5 of 56 or 8.9%; p less than 0.03). This was not the case for patients with LV ejection fraction less than 40%. Similarly, arrhythmic events were significantly reduced only in patients with preserved LV function. These results suggest an interaction between the effects of amiodarone on survival and LV dysfunction in patients after acute myocardial infarction. Because of 2 other small studies with similar results, this finding may be of clinical relevance and should be addressed in ongoing and future research with this drug. PMID- 1590227 TI - Incidence and timing of recurrences of sudden death and ventricular tachycardia during antiarrhythmic drug treatment after myocardial infarction. AB - Incidence and timing of recurrences of sustained ventricular tachycardia (VT) or sudden death were studied in 206 patients who survived their first episode of ventricular fibrillation (VF; n = 52) or sustained VT (n = 154) after myocardial infarction. All patients were treated with (empirically selected) antiarrhythmic drugs; 49% received amiodarone. After a mean follow-up of 36 months, 64 patients (41%) in the VT group and 10 (19%) in the VF group had nonfatal VT recurrences. Sudden death occurred in 22 (14%) and 9 (17%) patients in the VT and VF groups, respectively. Incidence of sudden death had 2 peaks at approximately 3 and 12 months. Nonfatal VT recurrences were more frequent (most often occurring in first 6 months) in the VT than in the VF group. Sudden death occurred during the following 3 years in only 10% of patients who survived 1 year. There was a much higher incidence of sudden death in patients with left ventricular ejection fraction (LVEF) less than or equal to 40% than in those with LVEF greater than 40% (28 of 65 vs 3 of 141; p less than 0.0001), but no relation between LVEF and nonfatal VT recurrences. PMID- 1590228 TI - Usefulness of pirenzepine, an M1 antimuscarinic agent, for effort myocardial ischemia. AB - This study evaluated the effect of pirenzepine, an M1 antimuscarinic agent, on exercise duration and ischemic threshold in patients with angiographically documented coronary artery disease and clear-cut ST depression (greater than 0.2 mV, 0.08 second after the J point) during ergometric stress testing. Twenty-five patients, mean age 56 +/- 8 years, underwent 3 randomized multistage bicycle exercise stress tests after intravenous administration of saline solution (2 ml), isosorbide dinitrate (1 mg) and pirenzepine (2 mg). Isosorbide dinitrate, an endothelium-independent coronary dilating agent, was used as a reference drug. Compared with saline, both pirenzepine and isosorbide dinitrate significantly improved time to ischemia (0.15 mV ST-segment depression) from 6.5 +/- 2 to 7.8 +/- 2 and 8.6 +/- 2 minutes and rate-pressure product at ischemia from 21,498 +/- 4,903 to 24,083 +/- 6,692 and 24,547 +/- 5,390 mm Hg.beats/min, respectively. Compared with saline, pirenzepine did not induce significant changes in blood pressure either at rest or during exercise, whereas it decreased resting heart rate from 71 +/- 9 to 60 +/- 11 beats/min (p less than 0.01) and induced a significant increment of heart rate during ischemia from 117 +/- 18 to 126 +/- 21 beats/min (p less than 0.05). Compared with saline, isosorbide dinitrate reduced systolic blood pressure at rest from 132 +/- 12 to 112 +/- 12 mm Hg, increased heart rate at rest from 71 +/- 10 to 84 +/- 16 beats/min and heart rate at ischemia from 117 +/- 18 to 132 +/- 16 beats/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590229 TI - Simultaneous transesophageal two-dimensional echocardiography and atrial pacing for detecting coronary artery disease. AB - This study describes a new technique for assessing wall motion abnormalities, combining transesophageal echocardiography (TEE) and transesophageal atrial pacing in 71 patients. Stable capture was reached in 70 patients (99%). In 3 patients (4%) pacing was discontinued prematurely because of discomfort. TEE during pacing was performed in 52 patients with and in 18 patients without coronary artery disease (CAD). In 43 of 52 patients with CAD, regional wall motion abnormalities occurred (sensitivity 83%). No wall motion abnormalities occurred in 17 of 18 patients without CAD (specificity 94%, positive predictive value 98%). Wall motion abnormalities related to another vascular region were observed in 17 of 22 patients with previous myocardial infarction (sensitivity 77%, specificity 100%, positive predictive value 100%). Simultaneous 12-lead electrocardiography during atrial pacing was performed in 57 patients and yielded positive results in 21 of 40 patients with (sensitivity 52%) and in 3 of 17 patients without (specificity 82%, positive predictive value 88%) CAD. Exercise stress testing was performed in 66 patients. Twenty-four of 48 patients with CAD had a positive exercise electrocardiogram (sensitivity 50%); a false-positive exercise electrocardiogram was observed in 3 of 18 patients (specificity 83%, positive predictive value 89%). It is concluded that TEE during transesophageal atrial pacing is a feasible and promising alternative technique for the assessment of CAD, with a higher sensitivity than simultaneous 12-lead and exercise electrocardiography. PMID- 1590230 TI - Outcome after prolonged balloon inflations of greater than 20 minutes for initially unsuccessful percutaneous transluminal coronary angioplasty. AB - Prolonged balloon inflation with or without autoperfusion techniques is a common initial approach to major dissection or abrupt occlusion after percutaneous transluminal coronary angioplasty (PTCA). To assess such a strategy in the setting of unsuccessful angioplasty, 40 patients who underwent prolonged balloon inflations of greater than 20 minutes between January and July of 1991 after initially unsuccessful angioplasty were studied. These patients (median age 59 years) underwent PTCA for progressive or unstable angina (16[40%]), symptomatic or asymptomatic residual stenosis after myocardial infarction (10[25%]), acute myocardial infarction (3[8%]), stable angina (3[8%]), reinfarction (2[5%]), and other indications (6[15%]). The significant stenoses were primarily in the proximal and midportions of the right coronary (53%), left anterior descending (30%) and left circumflex (17%) coronary arteries. Before prolonged balloon inflation, the longest single inflation was 11 +/- 6 minutes and the total time of all inflations was 17 +/- 8 minutes (mean +/- standard deviation). Stenosis was reduced from 91 +/- 9 to 68 +/- 16% before prolonged inflation. After prolonged balloon inflation of 30 +/- 9 minutes, the residual stenosis was 47 +/- 21% (p = 0.0001 vs value before prolonged inflation). Furthermore, improvements in the appearance of filling defects or dissections, or both, occurred in 19 patients (48%). Procedural success was obtained in 32 of 40 patients (80%). Coronary bypass grafting was performed in 8 patients (20%): 4 after unsuccessful PTCA (3 emergently) and 4 electively after initially successful PTCA. Although 5 patients had creatine kinase-MB elevations greater than 20 IU/liter after the procedure, only 1 sustained a Q-wave myocardial infarction. There were no deaths in the hospital.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590231 TI - Referral patterns and exercise response in the rehabilitation of female coronary patients aged greater than or equal to 62 years. AB - Gender-related differences in cardiac rehabilitation referral patterns and response to an aerobic conditioning program were examined in 226 hospitalized older coronary patients (aged greater than or equal to 62 years). Overall, the outpatient cardiac rehabilitation participation rate in this population was 21%. Older women were less likely to enter cardiac rehabilitation than were older men (15 vs 25%; p = 0.06), despite similar clinical profiles. This was explained primarily by a greater likelihood of primary physicians to strongly recommend cardiac rehabilitation to men. Before conditioning, women who entered cardiac rehabilitation were less fit than were men; peak oxygen consumption was 18% lower in women (16 +/- 5 vs 20 +/- 5 ml/kg/min; p = 0.02). However, both groups improved aerobic capacity similarly in response to a 12-week aerobic conditioning program, with maximal oxygen consumption increasing by 17% in women and by 19% in men. Thus, older female coronary patients are less likely to be referred for cardiac rehabilitation, despite a similar clinical profile and improvement in functional capacity from the training component. PMID- 1590232 TI - Amount of exercise necessary for the patient with coronary artery disease. PMID- 1590234 TI - Preoperative diagnosis of coronary artery disease in patients with valvular heart disease using technetium-99m isonitrile tomographic imaging together with high dose dipyridamole and handgrip exercise. AB - Forty-seven consecutive patients (mean age 61 +/- 8 years) referred for cardiac catheterization due to moderate to severe aortic (n = 30) or mitral (n = 17) valvular heart disease were examined by technetium-99m isonitrile tomography together with a high-dose dipyridamole infusion (0.7 mg/kg) and handgrip stress. Tomography did not identify coronary artery disease (CAD) in 3 of the 21 patients with angiographically proven disease (sensitivity 86%) and suggested false positive results in 5 of the 26 without the disease (specificity 81% and negative predictive accuracy 88%). No patient without angina pectoris and with negative scintigraphy (n = 14) had angiographically significant (greater than or equal to 50% diameter stenosis) CAD. Overall vessel sensitivity was 63%, and specificity was 92%. The frequency of side effects during the dipyridamole-handgrip test was only 7%. No serious complications occurred during stress tests. Thus, technetium 99m isonitrile tomographic imaging, together with high-dose dipyridamole and handgrip exercise, is a useful noninvasive method in excluding significant CAD in patients with valvular heart disease. PMID- 1590233 TI - Effect of direct, reflex and exercise-provoked increases in sympathetic tone on idiopathic ventricular tachycardia. AB - Exercise treadmill testing and direct enhancement of sympathetic influence with agents such as isoproterenol are often used to reproduce ventricular tachycardia (VT). The cardiac effects of, and arrhythmia responses to, graded exercise, isoproterenol infusion and lower body negative pressure (the latter 2 with and without atrial and ventricular stimulation) were studied in 11 patients with idiopathic VT. During maximal exercise, substantial increases in heart rate and blood pressure occurred, but only 2 of 9 exercised patients had VT (during recovery in both). During programmed stimulation alone, VT was initiated in 6 patients. During maximum levels of lower body negative pressure (-60 cm of water in most), mean systolic blood pressure decreased by 10 mm Hg, heart rate increased by 15 beats/min, and ventricular refractory period decreased by 10 ms. In 4 patients VT occurred spontaneously during lower body negative pressure; in 2, lower body negative pressure was the only intervention producing VT. During isoproterenol infusion VT occurred spontaneously in 2 patients; both had VT initiated during other interventions. Lower body negative pressure and isoproterenol increased VT rate, but did not prolong it. It is concluded that there is significant variability in arrhythmia responses to sympathetic augmentation, suggesting that additional covariables such as parasympathetic input and ventricular volume may also have a role in arrhythmia occurrence. PMID- 1590235 TI - Frequency of magnetic resonance signal abnormalities of the brain in patients aged less than 50 years with idiopathic dilated cardiomyopathy. AB - Twenty patients with idiopathic dilated cardiomyopathy (IDC) aged less than 50 years (mean 41) and an age-matched group of 20 healthy volunteers were studied. All subjects were free of cerebrovascular symptoms and risk factors for stroke. Magnetic resonance imaging of the brain, extracranial Doppler ultrasonography, heart catheterization and echocardiography were performed. In patients with IDC, a higher frequency of ventricular enlargement (p less than 0.02), cortical atrophy (p less than 0.01) and white matter lesions (p less than 0.05) was observed. Cerebral infarcts were found in 4 patients (p less than 0.05) who showed clinically severe limitation of functional capacity (New York Heart Association class III or IV). The extent of cortical atrophy, and the duration of clinical evidence of IDC showed a significant correlation (p less than 0.04). The data indicate a high incidence of parenchymal abnormalities of the brain in young, neurologically asymptomatic patients with IDC. PMID- 1590236 TI - Ventricular arrhythmias in dilated cardiomyopathy as an independent prognostic hallmark. Italian Multicenter Cardiomyopathy Study (SPIC) Group. AB - Prevalence and characteristics of ventricular arrhythmias (VA) on Holter monitoring were evaluated in 218 patients with invasively documented idiopathic dilated cardiomyopathy to clarify their relation to pump dysfunction, and their prognostic role. VA were observed in 205 patients (94%) and were high grade (ventricular pairs or tachycardia) in 130 (60%). No simple or multiform ventricular premature complexes were present in 88 patients (group 1; 41%), ventricular pairs in 63 (group 2; 32%), and ventricular tachycardia in 67 (group 3; 27%). Only echocardiographic right ventricular dimensions (p less than 0.05) and prevalence of VA during effort (8% in group 1, 15% in group 2, and 14% in group 3; p = 0.0005) differed significantly between groups. VA severity, and number of ventricular premature beats and tachycardia episodes were not correlated to right/left ventricular dimensions and pump function indexes. During a mean follow-up of 29 +/- 16 months, 27 patients died from cardiac events, and 16 received transplants. Three-year survival probability was lower in groups 2 (0.82) and 3 (0.81) than in group 1 (0.94). By Cox multivariate analysis, VA severity (p less than 0.01) was a major independent predictor of prognosis after markers of ventricular dysfunction such as left ventricular ejection fraction (p less than 0.001) and stroke work index (p less than 0.001). PMID- 1590237 TI - Prevalence and etiology of idiopathic dilated cardiomyopathy (summary of a National Heart, Lung, and Blood Institute workshop. AB - Idiopathic dilated cardiomyopathy (IDC) is the primary indication for cardiac transplantation, with associated costs of approximately $177 million per year. Recognizing the economic implications of IDC, the increasing incidence, and the limited information on pathogenesis and prognosis, the National Heart, Lung, and Blood Institute convened a workshop on the Prevalence and Etiology of Idiopathic Dilated Cardiomyopathy on June 13 to 14, 1991. The difficulties of studying the disease were reviewed, including its relatively low prevalence, its potentially pluricausal nature, and the fact that it is often a diagnosis of exclusion. Still, it presents significant challenges to the cardiovascular scientific community, since the mechanism of myocardial damage and related etiologic and prognostic factors are virtually unknown. The development of more reliable measures of immune-mediated damage and noninvasive measures of impaired cardiac function present new research opportunities in this disorder. Standardized diagnostic criteria for use in observational and interventional trials were developed, and priorities for future research were proposed. Population-based registries and nested case-control studies, where feasible, are appropriate study designs for tracking incidence and prevalence, and for identifying risk factors, respectively. Interventional studies should focus on secondary prevention, through modifying immune-mediated damage in clinically evident dilated cardiomyopathy, and through prevention of sudden death in patients with the disorder. Primary prevention trials must await the identification of modifiable risk factors and of appropriate and effective interventions. PMID- 1590238 TI - Outcome of prenatally detected cardiac malformations. AB - Reliable, prenatal detection of congenital heart disease has become possible over the past decade with the evolution of fetal echocardiography. We have documented the outcome of 170 cardiac defects diagnosed prenatally since 1984. Of 170 cases, 55 (32%) had major extracardiac malformations and 45 (28%) chromosomal abnormalities (16 had both). Elective termination was chosen in 77 (45%) pregnancies. Of 93 continuing pregnancies 15 were stillborn and 43 died postnatally (48% of these fetuses and infants had extracardiac or chromosomal anomalies, or both). Thirty-five patients survive at 1 to 80 months (mean 36). Aneuploidy or extracardiac defects are present in 20% of survivors. Nonimmune hydrops secondary to cardiac failure was present in 7 continuing pregnancies and none of these patients survived. The prognosis of prenatally diagnosed cardiac lesions is negatively influenced by the presence of cardiac failure, aneuploidy or extracardiac malformations, or a combination of these. Optimal counseling and management requires the identification of these conditions when present. PMID- 1590239 TI - Effect of balloon material on coronary angioplasty. PMID- 1590240 TI - Extent and severity of abnormal left ventricular wall motion detected by exercise echocardiography during painful and silent ischemia. PMID- 1590241 TI - Clinical significance of abrupt vasodepression during dobutamine stress echocardiography. PMID- 1590242 TI - Evaluation of coronary artery disease in the Hurler syndrome by angiography. PMID- 1590243 TI - Frequency of isolated panic attacks and panic disorder in patients with the mitral valve prolapse syndrome. PMID- 1590244 TI - Atypical systolic clicks produced by prolapsing mitral valve masses. PMID- 1590245 TI - Transesophageal versus transthoracic echocardiography for diagnosing mitral valve perforation. PMID- 1590246 TI - Abnormal blood rheology in idiopathic dilated cardiomyopathy. PMID- 1590247 TI - Left ventricular shape in idiopathic dilated cardiomyopathy and cardiomyopathy with or without only mild ventricular dilatation. PMID- 1590248 TI - Usefulness of the electrocardiogram and echocardiogram in predicting the amount of interstitial myocardial collagen in endomyocardial biopsy specimens of patients with chronic heart failure. PMID- 1590249 TI - Intravascular ultrasound imaging of Guenther vena caval filters. PMID- 1590250 TI - Maternal left ventricular performance during bicycle exercise. PMID- 1590251 TI - Usefulness of dynamic hand exercise for developing maximal separation of left and right ventricular pressures at end-diastole and usefulness in distinguishing restrictive cardiomyopathy from constrictive pericardial disease. PMID- 1590252 TI - Acute myocardial infarction triggered by emotional stress. PMID- 1590253 TI - Origin of the right coronary artery from the pulmonary trunk. PMID- 1590254 TI - Richard Lower: complete physician--scientist--pericardiologist. PMID- 1590255 TI - Comparative life spans of species: why do species have the life spans they do? AB - Proximate answers to questions about species longevity are to be found in the physiological processes that regulate duration of life. But what are these processes, and how are they themselves controlled? This leads to ultimate, evolutionary questions about longevity. What are the selection forces that favor one life span instead of another for a given species? To understand the evolution of life span we need also to understand the evolution of aging. A plausible hypothesis is that because of the requirement for reproduction, natural selection favors a strategy that invests fewer resources in maintenance of somatic cells and tissues than are necessary for indefinite survival. This "disposable soma" theory predicts that aging is due to the accumulation of unrepaired somatic defects and the primary genetic control of longevity operates through selection to raise or lower the investment in basic cellular maintenance systems in relation to the level of environmental hazard. PMID- 1590256 TI - Changes in life expectancy 1900-1990. AB - Life expectancy at birth has risen in all industrialized countries during the last 100 years, but mortality improvements by gender and region often have proceeded at very different rates. Although some countries have experienced increases in overall mortality during recent decades, the levels of life expectancy gains in countries such as Japan have confounded demographic predictions and have led to renewed research and debate over future mortality decline and the limits to human life. This paper reviews levels of and changes in life expectancy at birth and at older ages in industrialized countries during the 20th century. Trends in mortality and morbidity at older ages are summarized in the context of the historic epidemiological disease transition from infectious to chronic. Cause-specific and active/inactive decompositions of life expectancy are examined, as are initial attempts to correlate life expectancy with physical attributes that may reflect differential nutritional status. PMID- 1590257 TI - Changes in gastrointestinal function attributed to aging. AB - There are numerous reports in the literature of impaired gastrointestinal function with aging. However, most gastrointestinal functions remain relatively intact because of the large reserve capacity of the intestine, pancreas, and liver. Clinically important changes in gastrointestinal function with aging in human include decreased taste thresholds, hypochlorhydria due to atrophic gastritis, and decreased liver blood flow and size. Increased absorbability of lipids and large size molecules has been demonstrated in aging animals, but this has not been studied in humans. Nutrients with impaired gastrointestinal bioavailability in aging include dietary B-12, calcium carbonate, and ferric iron in atrophic gastritis; calcium, zinc, and possibly carbohydrate in a mixed meal. The implications of these changes for health maintenance and chronic disease in elderly people are in need of study. PMID- 1590258 TI - Apoptosis--programmed cell death: a role in the aging process? AB - Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances. PMID- 1590259 TI - Why are transformed cells immortal? Is the process reversible? AB - Normal cells have finite proliferative potential in culture. In contrast, cells derived from tumors immortalized by chemical carcinogens or viruses are able to divide indefinitely. A question of major importance is the mechanism that limits the proliferative potential of normal cells, and conversely, the process by which immortal cells have escaped irreversible growth cessation. To address this question we fused a number of different normal human fibroblast cell lines with various immortal human cell lines and determined the proliferative behavior of the resulting hybrids. In all cases the hybrids had a limited ability to proliferate in culture. These results suggested that the finite proliferative capacity of normal human cells was dominant and that immortal cells had acquired recessive changes in their genetic program, which allowed them to escape senescence. We were also able to assign approximately 30 immortal human cell lines to four complementation groups for indefinite division. PMID- 1590260 TI - Progeria: a human-disease model of accelerated aging. AB - Progeria is a rare genetic disease with striking features that resemble accelerated aging. The inheritance pattern, paternal age effect, and lack of consanguinity argue that it is due to a sporadic dominant mutation. We have observed elevated levels of hyaluronic acid (HA) excretion in progeria patients. In several progeria patients we observed normal levels of growth hormone (GH) but very low levels of insulin-like growth factor I along with very high basal metabolic rates (BMRs). A trial of GH treatment was begun, which resulted in a marked increase in linear growth and a paradoxical drop in BMRs in these two patients. We hypothesize that the failure of patients with progeria to thrive may be due to a bioinactive form of GH and a lack of vasculogenesis caused by excess HA. An understanding of the progeria genetic mutation may define a key gene with a major effect on normal aging. PMID- 1590261 TI - Diseases and aging: patterns of morbidity with age; relationship between aging and age-associated diseases. AB - Patterns of morbidity with age can be schematically represented in three situations: 1) as a progressive illness, such as Alzheimer's disease, leading to a relatively rapid functional decline. 2) as a catastrophic event, such as a stroke or hip fracture, leading to a decline in function with improvement after rehabilitation. 3) as normal aging with gradual progressive functional decline. Results from the New Mexico Aging Process Study provide some unique insights about the consequences of the effects of aging on the nutritional status of healthy elderly people. Between 1979 and 1989, anthropometric and biochemical markers as well as dietary intakes remained relatively constant in this healthy elderly population. Thus, the aging process alone may have little or no important consequences on the nutritional status of healthy elderly individuals. However, the adaptation of pancreatic and intestinal function to undernutrition and refeeding can be perturbed in these individuals. PMID- 1590262 TI - Physical activity and fitness. AB - There is unanimous agreement that regular exercise is essential for optimal function of the human body. It is evident that extrinsic factors, such as diet and exercise habits, are reflected in the morbidity and mortality statistics, especially in aging. Aging is obligatorily associated with reduced maximal aerobic power and reduced muscle strength, ie, with reduced physical fitness. As a consequence of diminished exercise tolerance, a large and increasing number of elderly people will be living below, at, or just above "thresholds" of physical ability, needing only a minor intercurrent illness to render them completely dependent. Physical training can readily produce a profound improvement of functions also essential for physical fitness in old age. From a nutritional viewpoint one advantage of physical activity, and increased metabolic rate, is that a higher energy intake can better secure an adequate intake of essential nutrients. PMID- 1590263 TI - Nutritional factors in physical and cognitive functions of elderly people. AB - The quality of life of aging individuals depends profoundly on their capacity for physical mobility, mental alertness, and cognitive function. Independence and self-esteem are strongly determined by physical and mental capacities. Stimulated by reports of declining function with age, investigators have examined the relationships between lifestyle factors and maintenance of functional status. Growing evidence supports the view that continued physical activity and good nutritional status are important determinants of physical and cognitive function. It is possible that some of the decline in cognitive function associated with aging is preventable or reversible with improved vitamin nutriture, especially vitamin B-12, vitamin B-6, and folate. It might well be argued that the most practical outcome of research on the relationship of diet and nutrition to the aging process would be a better understanding of the ways in which our behavior can maintain a vigorous quality of life. PMID- 1590264 TI - Nutrition and genetic susceptibility to common diseases. AB - Genetic factors play a role in chronic disease and conditions such as coronary heart disease, hypertension, and obesity. Individual responses to nutritional factors involved in such conditions vary depending upon a person's genetic make up. The role of individual genes is best understood for the hyperlipidemias that predispose to coronary heart disease. Until more and better information on gene nutritional interactions is available, general population-wide recommendations regarding a prudent diet appear reasonable. At the same time, high risk screening for certain conditions such as the hyperlipidemias is appropriate. PMID- 1590265 TI - Physiological processes of aging: are there special nutritional requirements for elderly people? Do McCay's findings apply to humans? AB - Aging is characterized by shrinkage of muscle fibers and loss of protein from them. Bone is also lost, and matrix and mineral are lost together. The predominance of breakdown over synthesis is probably the fundamental cause of both muscle and bone loss. Little can be done to prevent this by dietary means, but physical activity is of vital importance in helping to maintain the integrity of both muscle and bone. McCay's finding that rats underfed from weaning lived longer than those that had adequate food has been confirmed by others, but this is only true if the rats remain free of infections and other hazards, particularly during growth. The mechanisms by which underfeeding delays the aging process in rats may apply to the human body but, if so, this is completely offset by other considerations. For their present and future well-being, children should be fed in the best possible way. PMID- 1590266 TI - Retardation of aging processes by food restriction: an experimental tool. AB - The importance of food restriction in rats, mice, and hamsters as a tool for the study of aging is discussed. The evidence that food restriction retards the aging processes is summarized and includes its ability to extend the maximum life span, to decrease the rate of increase in age-specific mortality, to retard age changes in physiological processes, and to delay or prevent most age-associated diseases. Food restriction has its anti-aging action by reducing the intake of energy rather than a specific nutrient. Research findings on the possible mechanisms by which food restriction retards the aging processes are discussed. The use of food restriction to test theories of aging is described and the controversial issue of its possible use as an intervention of human aging is addressed. PMID- 1590267 TI - Nutrition and the quality of life: a measure for the outcome of nutritional intervention.? AB - The quality of life in old age is dependent on many resources and not just on health. Quality of life cannot be a measure for the outcome of nutritional interventions in old age. Risk patterns shift with advancing age and the outcome of a nutritional intervention may have to be evaluated under different circumstances. Although the impact of nutrition as a preventive measure decreases with age, the value of food intake for social structure, self-esteem, enjoyment, and situation awareness gradually increases. PMID- 1590268 TI - Quality of life: can it be an endpoint? How can it be measured? AB - Although quality of life is an elusive concept constantly in flux, it is possible to identify certain basic criteria whose presence or absence determines the degree of quality in an older person's life. It is possible through a variety of measures to improve quality of life on both a personal and societal level. Improvements will be even greater once the major diseases of old age are conquered. We can get closer to that goal with greater investments in research on aging. PMID- 1590269 TI - Chemotherapy of cervix cancer with mitolactol (dibromodulcitol, NSC 104800) and cisplatin. A phase I study of the Gynecologic Oncology Group. AB - In this Phase I study, thirteen women with advanced cervix cancer were treated with mitolactol (dibromodulcitol) plus cisplatin to determine a maximum tolerable dose schedule. Response was not an objective of this study, but four partial responses were seen in nine patients with measurable lesions. In general, the therapy was well tolerated, but of the ten patients treated at the first dose level (cisplatin 50 mg/m2 intravenously on day 1 plus mitolactol 180 mg/m2 orally on days 2-6 every 3-4 weeks), 5 required de-escalations and 8 required delays because of toxicity. All three patients treated with cisplatin plus a higher dose of mitolactol (270 mg/m2 x 5) required dose reductions and delays for hematologic toxicity. The first dose level appears tolerable by patients with, and promising in treating, advanced cervix cancer. PMID- 1590270 TI - Intraarterial infusion chemotherapy with [Sar1,Ile8]angiotensin II for bladder cancer. AB - Thirty-three patients with primary bladder cancer (nine stage T1 with multifocal tumors and 24 stage T2-4) were treated with intraarterial infusion chemotherapy including cisplatin, doxorubicin, and [Sar1,Ile8]Angiotensin II(AT II). Of the 32 evaluable patients, 12 had pathologically proven complete response (CR), 19 showed partial response (PR), and one showed no change (NC); the overall response rate (CR + PR) was 97%. The blood pressure increased in response to the administration of [Sar1,Ile8]AT II in all the patients; the mean increase in the systolic blood pressure was 36 mmHg. Most of the side effects were mild to moderate in severity, transient in nature, and included nausea/vomiting (100%), alopecia (84%), leukopenia (66%), headache (9%), nephrotoxicity (6%), diarrhea (3%), skin pigmentation (3%), and neurotoxicity (3%). One patient who dropped out of the study developed hemiplegia as a result of cerebral infarction. The findings indicate that it is necessary to exercise caution in selecting the patients to be subjected to this therapy. We conclude that intraarterial infusion chemotherapy combined with a vasoconstrictor has a significant effect not only against multifocal superficial bladder cancer but also against invasive bladder cancer. PMID- 1590272 TI - Treatment of medulloblastoma in adults. AB - Seventeen adult patients with medulloblastoma were treated at Rush-Presbyterian St. Luke's Medical Center and affiliated hospital between 1969 and 1986. All patients had a surgical procedure (total excision in seven patients, partial resection in nine patients, and biopsy alone in one patient) followed by radiation therapy to the craniospinal axis. The 5-year actuarial survival rate is 77% with a disease-free survival of 58%. Five patients have relapsed in the posterior fossa, one in the brain parenchyma, and two in osseous sites. Two of the local relapses occurred more than 4 years after initial treatment. Patients undergoing "total" resection of the tumor fared better than those with partial resection or biopsy only. Local failure was uncommon with posterior fossa doses greater than 55 Gy, and there was a trend toward better local control when the radiation therapy was completed in less than 7 weeks. The histologic indicators of poor outcome were necrosis, high mitotic index, and "classical" histologic appearance. PMID- 1590271 TI - Comparison of radiation therapy of classic and epidemic Kaposi's sarcoma. AB - Between 1963 and 1990, 92 lesions in twenty patients with Kaposi's sarcoma (KS) were treated using radiation therapy (RT). Fifty-nine classic Kaposi's sarcoma (CKS) lesions in 12 patients were treated with 990 cGy in 3 fractions-5,000 cGy in 25 fractions; 39 lesions (66%) showed a complete response (CR), 15 (25%) showed a partial response (PR) with complete symptomatic relief, and 5 lesions (8%) showed no response (NR). Only 6 of 59 lesions (10%) recurred in field with a median recurrence-free duration of 8 months. Thirty-three epidemic Kaposi's sarcoma (EKS) lesions in 8 patients were treated from 1,000 cGy in 5 fractions 3,000 cGy in 10 fractions. Thirty-one EKS lesions (94%) showed CR, and two lesions (6%) showed PR. An extensive review of the literature is also presented in the study here reported. PMID- 1590273 TI - Radiation resistance in a doxorubicin-resistant human fibrosarcoma cell line. AB - In clinical practice, cancers refractory to chemotherapy can appear relatively radioresistant. Recent work in multidrug-resistant cell lines has yielded conflicting results concerning the relationship between drug resistance and radiation resistance. The current study examines the radiation response of a human fibrosarcoma (HT1080) and a doxorubicin-resistant subline (HT1080/DR4). Using soft-agar colony formation after graded doses of x-rays as an endpoint, HT1080/DR4 had an increased D0 (D0 = 2.1 Gy) and a broader initial shoulder (n = 2.7, Dq = 2.1 Gy) than the parental HT1080 line (D0 = 0.7, Gy, n = 1.2, Dq = 0.3 Gy), suggesting that HT1080/DR4 has an increased capacity to repair radiation induced DNA damage. This possibility was tested by comparing the cell lines' ability to accumulate sublethal damage. In split-dose recovery experiments, HT1080/DR4 demonstrated increased ability to repair sublethal radiation damage following fractionated irradiation, compared with the HT1080 parental line. The mechanism for this radiation resistance is not clear, but a variety of cellular alterations seen in drug-resistant cell lines are discussed with reference to areas of further study. PMID- 1590274 TI - Primary non-Hodgkin's lymphomas of the paranasal sinuses and nasal cavity. A report of 18 cases with stage IE disease. AB - During a 26-year period (1961-1987), a total of 18 patients with primary non Hodgkin's lymphoma (NHL) of the paranasal sinuses and nasal cavity received radiation therapy at (University of California at Los Angeles) UCLA Medical Center. At the time of diagnosis and using the available diagnostic methods, none of these patients had clinically detectable disease beyond the paranasal sinuses. All 18 patients were staged IE by the Ann-Arbor system. When the patients were staged according to the AJC staging system from epithelial tumors, half presented with advanced T3-4 disease. Diffuse histiocytic lymphoma was the most common histology (eight cases) and maxillary sinus, the most common site of origin (11 cases). All nine T1-2 tumors received radiation therapy alone, while radiation and chemotherapy was used in seven of nine advanced T3-4 staged tumors. The mean follow-up was 71 months. At last follow-up, eight of nine T1-2 patients were rendered disease-free. In contrast, only four of nine T3-4 patients had long-term disease-free survival. Seventy-five percent of the failure occurred within 2 years. Radiation therapy alone achieves high local control in small tumors (T1 2), while large tumors (T3-4) require aggressive combined treatment, i.e., radiation and chemotherapy. PMID- 1590275 TI - 131-I-metaiodobenzylguanidine treatment in patients with refractory advanced neuroblastoma. AB - Fourteen patients with refractory advanced neuroblastoma were treated with 131-I metaiodobenzylguanidine (131-I-MIBG); all had evidence of progressive disease or recurrent disease following combination chemotherapy. One patient without gross evidence of disease, following surgical resection of recurrent neuroblastoma before therapy with 131-I-MIBG, remains healthy without regrowth of tumor 3.5 years later. Two other patients had minor responses, and one had a mixed response. Two patients remain alive 1,212 and 1,926 days following the initial 131-I-MIBG treatment; the remaining 12 patients died of progressive disease. Moderate myelosuppression was the most notable toxicity observed; mild nausea and vomiting and transient mild liver enzyme elevation were also encountered. Treatment with 131-I-MIBG produced antineoplastic activity in patients with neuroblastoma and was well tolerated. To evaluate dose escalation, alternative dosage schedules, and alternative MIBG-radioconjugates, additional trials of radiolabeled MIBG are indicated. PMID- 1590276 TI - Fluoxymesterone as third line endocrine therapy for advanced breast cancer. A phase II trial of the Piedmont Oncology Association. AB - The Piedmont Oncology Association conducted a Phase II trial of fluoxymesterone (Halotestin) in 28 patients who failed to respond to prior hormonal therapy with tamoxifen and a progestational agent. Of nine patients who had responded to prior endocrine therapy, one had a partial response (PR) as defined by strict criteria and remains on study at 17 + months for an 11% response rate [95% confidence interval (CI), complete response (CR) + PR, 0-48%]. None of 19 previously unresponsive patients achieved remission (95% CI, CR + PR, 0-18%). Eleven patients' performance status deteriorated during therapy. Five of them had not received prior chemotherapy, and their response to subsequent chemotherapy may have been adversely affected. Third-line hormonal therapy with fluoxymesterone can be recommended only as a temporizing measure in patients with indolent disease who have responded to prior hormonal therapy. PMID- 1590277 TI - A phase II study of intravenous 6-thioguanine (NSC-752) in advanced colorectal carcinoma. AB - Fifteen patients with advanced measurable colorectal carcinoma were treated with intravenous 6-thioguanine (6-TG) at a dosage of 55 mg/m2 for 5 consecutive days every 5 weeks. Only one patient had received prior adjuvant chemotherapy. No responses were detected, and eight patients had stable disease for a medium duration of three treatment cycles. Toxicity was tolerable. We conclude that 6-TG given by this dosage schedule is ineffective in treating metastatic colorectal carcinoma. PMID- 1590278 TI - A phase II trial of continuous infusion cisplatin and 5-fluorouracil with oral calcium leucovorin in colorectal carcinoma. AB - Twenty previously untreated patients with advanced colorectal adenocarcinoma were entered on a Phase II trial of 3-day continuous infusion cisplatin (25 mg/m2/day) and 5-fluorouracil (800 mg/M2/day) with oral calcium leucovorin (30 mg/dose) every 6 hours. There were four partial responses (20%) and two complete responses (10%) for a total response rate of 30% (95% confidence limits +/- 20%). Patients received a median of 4.5 cycles of therapy (range 2-9 cycles). Three patients experienced neutropenia; one had a life-threatening infection. One developed neuropathy at 375 mg/M2 cumulative dose. Four patients developed mucositis. Treatment was stopped for one patient with stable disease after 5 cycles because of anorexia and nausea and vomiting; treatment was stopped for four patients because of excessive fatigue. The median duration of responses was 4 months (range 3-6 months). Although this regimen is active, the response rate, cumulative nature of the toxicity, and the requirement for hospitalization led us to conclude that this regimen does not warrant Phase III testing but might be a basis for further Phase II therapeutic trials. PMID- 1590279 TI - Synchronous radiotherapy and chemotherapy with cisplatin in the management of locally advanced or recurrent head and neck cancer. AB - A synergism between cisplatin and radiotherapy has been demonstrated in in vitro and in vivo studies. To improve the locoregional control of disease and the survival rate in patients affected by locally advanced or recurrent squamous cell carcinoma of the head and neck, we planned a Phase II study of concurrent radiotherapy, 2 Gy for 5 days every week for a total dose of 60-70 Gy with cisplatin 80 mg/m2 every 21 days for 2 or 3 doses (on days 1, 21, 42). Fifty-one patients were entered in the study; 48 were evaluable for response and toxicity; 18 (37.5%) had untreated Stage III disease; 25 (52%) had Stage IV disease; 5 (10.5%) had recurrent disease. The complete response rate in Stage III-IV patients was 63% (27 of 43) with 95% confidence limits from 48 to 77% (+/- 14.5%). In the group of five patients with recurrent disease, only one (20%) achieved a complete response. In patients with Stage III-IV disease, a significantly higher complete response rate was observed for those younger than 58.5 years (p = 0.05). The overall estimated 1- and 2-year survival was 59% and 37%, respectively, and a significantly better survival was observed in complete responders compared to partial responses or patients with stable disease (p = 0.037). Disease-free survival was 46% and 36% at 1 and 2 years, respectively. Distant failure occurred only in 12.5% of the patients. Overall, the treatment was well tolerated, and only three patients refused to complete the planned therapy. Gastrointestinal and hematological toxicity were the most common side effects. Data from present trial were compared with that of 50 patients with comparable characteristics treated with radiotherapy alone from 1985 to 1987 as a historical control. The complete response rate, the disease-free survival, and the overall survival appear to be better in the patients treated with chemoradiotherapy. It was concluded that the combination of chemoradiotherapy in patients with Stage III-IV head and neck squamous cell carcinoma is an effective and safe treatment with an apparent better locoregional control than radiotherapy alone. Survival results need to be evaluated in a Phase III randomized trial. PMID- 1590280 TI - Hyperfractionated radiation therapy and concurrent 5-fluorouracil, cisplatin and mitomycin-C in head and neck carcinoma. A pilot study. AB - Seventeen patients were entered into a Phase I/II trial of concurrent hyperfractionated radiation therapy (7,440 cGy total dose; 120 cGy b.i.d.) combined with constant infusion of 5-fluorouracil (5-FU) (1,000 mg/m2/24 hours for 72 hours) and cisplatin (DDP) (50 mg/m2) for a total of three cycles. Thirteen patients had Stage IV disease; three, Stage III disease; and one, Stage II hypopharyngeal disease. Thirteen of 17 patients had positive cervical lymph nodes, and the mean size of the largest lymph node was 5.5 x 5.1 cm. The patients were not treated with planned adjunctive surgery except for one patient who had a radical neck dissection for massive, rapidly growing cervical adenopathy, which recurred promptly within 1 month before the initiation of protocol therapy. After the initial six patients were entered, mitomycin-C (Mito 8 mg/m2) was added during the second cycle. All the patients completed the planned course of radiotherapy with a median dose of 7,440 cGy and a mean dose of 7,248 cGy except for two patients who died--one from toxicity and the other, suicide. The predominant toxicity was mucositis, which was grade 3/4 in 11 of 15 patients, resulting in an average interruption of radiation therapy of 12 days. Weight loss was significant and was on the average 12% of baseline weight. Hematological toxicity was mild in the 5-FU/DDP group (only one grade 3 toxicity of six) and severe in the 5-FU/DDP/Mito-treated patients (five of eight patients having grade 3/4 toxicity including one leukopenic pneumonitis death). Additional toxicity included one parapharyngeal cellulitis, which responded to antibiotics. Noncompliance with the complex regimen was only seen in three patients. One patient refused b.i.d. radiation therapy, and one patient refused further chemotherapy after the first cycle. Additionally, one patient who had a severe ethanol withdrawal reaction during the first cycle of 5-FU/DDP did not receive further chemotherapy. The complete response rate of both primary site and neck by the protocol regimen alone was 71%. However, two patients, one from each group, did undergo salvage neck dissection, and the locoregional control is currently 73%, with a mean follow-up time of 18.4 months. The feasibility of combining hyperfractionated radiation therapy with aggressive concurrent chemotherapy was demonstrated. The response and local control rate justifies the added toxicity of concurrent chemotherapy and radiation therapy. PMID- 1590281 TI - Phase II trial of recombinant tumor necrosis factor in disseminated malignant melanoma. AB - Twenty-one patients with disseminated malignant melanoma received recombinant tumor necrosis factor (TNF), 150 micrograms/m2 intravenously on days 1-5 every 2 weeks for four cycles and then every 3 weeks. Recombinant TNF produced no meaningful palliation. One patient (5%) attained an objective response of nodal, but not visceral, disease, which lasted 3 weeks. The median time to progression was 4 weeks. The median survival was 7.7 months. Ninety percent of patients developed mild to severe cytokine "flu." Ten percent developed significant hepatic toxicity (AST greater than 3 times normal). As a single agent, recombinant TNF is not likely to palliate disseminated malignant melanoma. However, combinations of recombinant TNF and cytotoxic or immune modulatory agents, particularly gamma interferon, may merit further investigation. PMID- 1590282 TI - Aminoglutethimide in malignant melanoma. A phase II study. AB - The role of steroid hormones has been suggested in the growth of malignant melanoma, and since aromatase activity has been found in melanoma tissue, we carried out a phase II study of aminoglutethimide, an aromatase inhibitor in malignant melanoma patients. Fifteen heavily pretreated patients entered the study. No response was observed--the treatment was well tolerated. We concluded that aminoglutethimide is very unlikely to be useful in melanoma patients. PMID- 1590283 TI - Variables contributing to anticipatory nausea and vomiting in cancer chemotherapy. AB - Forty cancer patients receiving parenteral chemotherapy were assessed for characteristics associated with the development of anticipatory nausea and vomiting (ANV). The patients who developed ANV were more likely to have increased pretreatment anxiety (p less than 0.05), greater posttreatment dizziness/lightheadedness (p less than 0.01), more severe postchemotherapy vomiting (p less than 0.01), and a delayed onset of postchemotherapy nausea and vomiting (PCNV) compared to the patients who developed neither ANV nor PCNV. However, when patients who did not develop PCNV were excluded from the analysis, the difference between the ANV and non-ANV patients remained significant only for postchemotherapy dizziness/lightheadedness (p less than 0.05). In an attempt to identify a group of variables that better predict the development of ANV, we analyzed the data for combinations of variables. Two indices were found to correctly classify ANV and non-ANV patients 71% of the time (p less than 0.05). Index A refers to the presence of at least two of the following variables, pretreatment anxiety, posttreatment dizziness/lightheadedness, and latency of PCNV. Index B refers to the presence of at least two of the following variables: pretreatment anxiety, severity of nausea, and severity of vomiting. The identification of characteristics associated with the development of ANV could lead to new intervention strategies. PMID- 1590284 TI - A controlled study of sustained-release morphine sulfate tablets in chronic pain from advanced cancer. AB - The purpose of this double-blind crossover study was to determine whether a sustained-release morphine sulfate (SRMS) tablet given orally every 12 hours could adequately replace immediate-release morphine sulfate solution (IRMS) given orally every 4 hours in hospitalized patients with chronic pain from advanced cancer. Of 33 patients entered, 27 completed the study and were included in the efficacy and safety analysis. Patients were initially randomized to receive either 30-mg SRMS tablets every 12 hours or IRMS at the same mg/24 hours dose, every 4 hours. After 2 days, a crossover was performed, and patients received the alternate treatment for 3 days. Pain and side effects were assessed using a standard 100 mm visual analogue scale (VAS). There were no statistically significant differences between the two treatment groups for mean VAS pain scores or scores for sleepiness, nausea, depression, and anxiety. The incidence of breakthrough pain was similar for both treatment groups, as was the incidence of confusion and constipation. The results demonstrated that SRMS is a safe, effective analgesic preparation for patients who require oral opioids for cancer pain. The data also support the conclusion that sustained-release morphine tablets administered every 12 hours can replace an immediate-release morphine solution administered every 4 hours. PMID- 1590286 TI - Comment on TMJ treatment. PMID- 1590285 TI - Acanthosis nigricans and severe insulin resistance in an adolescent girl with thyroid cancer: clinical response to antineoplastic therapy. PMID- 1590287 TI - Long-term occlusal guidance of a severely intoxicated patient with yusho (PCB poisoning): a case report. AB - The peculiar dentoorofacial characteristics and 12 years of interdisciplinary management of a patient who was severely intoxicated with the man-made chemical polychlorinated biphenyls (PCBs) are described in this case report. Cephalometric measurements showed that the SNA and SNB angles were reduced but that the developments in height and skeletal maturity were in normal ranges. Gingival hyperpigmentation that was caused by high blood PCB concentration was extremely slow to fade. A cystic mass, diffused trabeculae, and irregular calcification, which were shown on the radiograph and which were caused by high blood levels of PCB, changed gradually. However, the patient had periodontal disease because of horizontal alveolar bone resorption and a deep periodontal pocket, despite good plaque control. After the PCB poisoning the tooth roots were hypoplastic and dilacerated. One root was extracted because of chronic periodontitis. Some teeth were impacted, malposed, or ankylosed. PMID- 1590288 TI - Reducing white spot lesions in orthodontic populations with fluoride rinsing. AB - A clinical study was conducted to determine if rinsing frequency with a neutral 0.05% sodium fluoride rinse influenced white spot lesion formation associated with orthodontic brackets. Patients from two private orthodontic practices participated. Each received home-care instructions and were told to use 10 ml of sodium fluoride rinse daily before bedtime. The rinse was supplied free of charge to determine if this affected compliance with its prescribed use. Compliance was measured by recording the number of bottles used by each patient. As assessment of oral hygiene status was conducted, and at the time of debonding, white spot lesions were recorded. Only 13% of the 206 participants fully complied with the rinse protocol; 42% of the subjects used 10 ml approximately every other day; and 45% used the rinse less frequently. A significant dose response relationship was noted in which those who rinsed at least once every other day had fewer lesions (21%) than those who rinsed less frequently (49%). It was concluded that a significant reduction in enamel white spot lesions can be achieved during orthodontic therapy through the use of a 10 ml neutral sodium fluoride rinse. The more closely patients complied with the prescribed use, the more likely they could expect a decrease in the occurrence of lesions. PMID- 1590289 TI - Clinical effect of subgingival chlorhexidine irrigation on gingivitis in adolescent orthodontic patients. AB - Twenty-three adolescent orthodontic patients with gingivitis affecting all banded first molars volunteered for the study. Three measures associated with gingivitis (papilla bleeding index, plaque index, and probing depth) were recorded at four sites for all four molars. A single application of subgingival irrigation with 0.12% chlorhexidine digluconate or isotonic saline was performed for 5 seconds at each site. As determined by coin toss, the first molars on the right or left side of the mouth received either chlorhexidine or saline irrigation. The papilla bleeding index, plaque index, and probing depth were recorded before the treatment and subsequently at 2 weeks and then 4 weeks. The gingival bleeding as determined by papilla bleeding index, was virtually eliminated in 4 weeks by a single application of subgingival irrigation with either chlorhexidine or saline. However, there was no significant reduction in pocket depth or plaque index. In addition, no significant difference between the effect of chlorhexidine or saline was found for any of the outcome measures. PMID- 1590290 TI - Enamel fluoride uptake from an experimental fluoride-releasing orthodontic adhesive. AB - The purpose of this study was to evaluate quantitatively the fluoride uptake by enamel from an experimental visible light-cured orthodontic adhesive (VP-862) based on YbF3 filler. Sixteen contralateral premolars were extracted from 10 orthodontic patients and were classified in four groups (A, B, C, D) of four buccal surfaces each. Standardized enamel areas located on these surfaces were acid etched and were subjected to the following adhesive treatments: (A) VP-862; (B) Heliosit Orthodontic; (C) Heliobond + VP 862; and (D) Heliobond + Heliosit Orthodontic. Groups B and D were used as a reference. After 9 months in vivo, the teeth were extracted and cross-sectioned, and the enamel-adhesive interfaces were studied by combined wavelength-energy dispersive electron probe microanalysis. According to the results, the cumulative fluoride uptake by enamel from the experimental adhesive was not statistically different from the fluoride detected in the reference groups. No effect of the liquid resin, Heliobond, on the fluoride uptake gradients of enamel could be differentiated. PMID- 1590291 TI - The influence of extraction and nonextraction orthodontic treatment on brachyfacial and dolichofacial growth patterns. AB - The effects of extraction and nonextraction orthodontic treatment mechanics on patients with dolichofacial and brachyfacial growth patterns between one and two standard deviations were studied. Groups underwent treatment of either nonextraction or extraction of four premolars with the appropriate mechanics for the facial type. Changes in the facial axis and correlation between maxillary molar movement and facial axis change were measured. A positive correlation was found between the amount of anteroposterior movement of the upper molar and change in the facial axis in brachyfacial and dolichofacial patients undergoing nonextraction treatment. A weak correlation was found in the extraction treatment groups. No statistically significant difference was found in the facial axis change among any of the groups studied, regardless of facial type or plan of treatment. There were indications of a more severe opening of the facial axis (Ba Na plane to constructed gnathion) with greater degrees of maxillary molar distal movement in both facial patterns studied. PMID- 1590292 TI - A three-dimensional measuring system for the human face using three-directional photography. AB - This study was intended to develop a three-dimensional measuring system of the human face for clinical use, to ensure a high precision and a simple input operation by means of a personal computer and to measure the degree of its accuracy. With this system, it is possible to measure automatically two dimensional coordinates of hundreds of grid points on photographs of the human face with an image scanner as a reading device and to calculate their three dimensional coordinates with a computer. An orthognathic surgical case illustrates this technique in which the patient's face is displayed before and after the surgery on a cathode-ray tube (CRT), with the three-dimensional coordinates obtained with this system. A cubic plaster cast with a certain degree of irregularity has been constructed to measure the precision of this system. Comparison was then made between the three-dimensional coordinates obtained with this system and the coordinates obtained with the contact three-dimensional measuring system. The mean of errors and the standard deviation were 0.04 +/- 0.24 mm for the X coordinate, 0.03 +/- 0.16 mm for the Y coordinate, and 0.08 +/- 0.23 mm for the Z coordinate. Thus the accuracy of this system is high enough for the measurement of the human face. PMID- 1590293 TI - A mathematical model for the computation of the forces exerted by the facial orthopedic mask. AB - This study presents a model for the computation of the forces exerted on the chin and on the forehead by the facial orthopedic mask in skeletal Class III malocclusions. Cephalometric data as well as geometry of the mask are taken into account to simulate in quantitative terms the entire approach. A computer program has been implemented to validate the model on a group of patients. Despite the approximations about the mechanical characteristics of the appliance and of the constraints (rigid body, ideal constraints) and despite the unavoidable errors in the estimation of the geometric parameters (dimensions and angles), it is shown that the computation of the forces (in orientation and in magnitude) at the forehead and at the chin is possible. Some practical applications of the model are presented. PMID- 1590294 TI - Cervical and craniocervical posture as predictors of craniofacial growth. AB - The present study aimed to determine whether growth changes in craniofacial structure could be predicted by variables expressing the postural relations of the head and the cervical column. The sample comprised 34 children, 16 girls and 18 boys. Cephalometric radiographs obtained in natural head position (mirror position) were taken on two occasions before orthodontic treatment. Mean age was 9.9 years at time 1 and 12.7 years at time 2. Selection of the sample was based on skeletal maturity at time 2 indicating peak activity in pubertal growth. Forty one reference points and four fiducial points were digitized on each film. Individual growth changes in craniofacial structure were determined by computerized structural superimposition of the digitized sets of points. Correlation coefficients were calculated between 11 postural variables at the first observation and the subsequent growth rate in 36 structural variables. Uniform fields of low to moderate correlation coefficients significant at the 5%, 1%, and 0.1% levels (0.3 to 0.6) were found for eight structural variables, indicating that a small craniocervical angle and a backward-inclined upper cervical column at time 1 was associated with horizontal facial development characterized by reduced backward displacement of the temporomandibular joint (TMJ), large maxillary growth in length, increased facial prognathism, and larger than average true forward rotation of the mandible; whereas, a large craniocervical angle and an upright position of the upper cervical column at time 1 was associated with vertical facial development characterized by large backward displacement of the TMJ, reduced growth in length of the maxilla, reduced facial prognathism, and less than average true forward rotation of the mandible. The findings are in agreement with a theoretical model for the developmental interaction between head posture and facial structure. PMID- 1590295 TI - A static occlusal analysis based on ideal interarch and intraarch relationships. AB - Study models were visually assessed to quantify the number of ideal tooth relationships actually present relative to the potential total. Both intraarch and interarch relationships were used to generate an ideal tooth relationship index (ITRI). Index scores were generated for the entire dentition, which could be divided into anterior, posterior, interarch, and intraarch relationships. Index scores were determined at various time intervals so the longitudinal changes could be studied. Treated orthodontic cases (n = 92) showed an initial total ITRI score of 26% that increased to 52% at the end of orthodontic treatment and continued to improve to 59% during the retention and postretention periods. Anterior segment scores were higher (64%) than posterior segment scores (44%). The intraarch relationships of the anterior segment registered the highest (75%), whereas the lingual cusp relationships of the posterior segment had the lowest scores (35%). Various types of malocclusions exhibited different ITRI scores before treatment but responded equally to treatment showing similar improvement in scores at the end of treatment and the posttreatment period. PMID- 1590296 TI - Data and patterns of transverse dentofacial structure of 6- to 15-year-old children: a posteroanterior cephalometric study. AB - The aims of the present cross-sectional investigation were to provide normative data of selected dentofacial posteroanterior cephalometric measures and to describe the patterns of transverse dentofacial structure. The material comprised the P-A cephalograms of 588 Austrian schoolchildren (157 girls and 431 boys, who were 6 to 15 years old). All subjects were healthy, presented various types of occlusions, and did not receive orthodontic or orthopedic therapy. In studying the P-A cephalograms, 8 linear and 2 angular variables, as well as 10 ratios were used. The results of the study revealed that all skeletal widths and all ratios representing relations between the various breadths of the facial skeleton and the interorbital width demonstrated an increase when the measurements at the initial and final ages of 6 and 15 years, respectively, were compared. However, the maxillary intermolar width during the period from 9 to 12 years did not present any increase, and the mandibular intermolar width remained approximately the same during the whole observation period. The transverse dentoalveolar relationship in the incisal region remained very symmetric during aging. The standard deviations of most cephalometric variables were small when they were compared with their corresponding mean values. The present data are of value for the diagnosis of various types of dentofacial anomalies, for monitoring growth of persons or groups of corresponding age and race, and for comparison with other studies. PMID- 1590297 TI - A crisis in orthodontists? It's time to look within. PMID- 1590299 TI - ABO certification--a worthy goal. PMID- 1590298 TI - The end of an era. PMID- 1590300 TI - Orthodontic practice in the 90s "The second golden age". PMID- 1590301 TI - Nausea and vomiting of pregnancy and the electrogastrogram: old disease, new technology. PMID- 1590302 TI - 1991 Henry Baker Presidential Lecture. Colitis in the elderly. PMID- 1590303 TI - Evaluation of the small intestine by enteroclysis for Crohn's disease. AB - We reviewed the records of 100 consecutive patients referred for enteroclysis by gastroenterologists because of suspected Crohn's disease of the small bowel to assess the clinical utility of the information obtained by this method. More than one-third of the patients in the study group had subtle lesions of early Crohn's disease, all patients who required surgery had severe disease by radiologic criteria, and none of the 34 patients clinically suspected of having Crohn's disease of the small bowel in whom the enteroclysis was normal developed Crohn's disease in two or more years of clinical follow-up. Enteroclysis provides gastroenterologists with accurate and detailed structural information relevant to the appropriate management of the disease and in our hands is a reliable test for excluding Crohn's disease of the small bowel. PMID- 1590304 TI - Gastric myoelectrical activity in the first trimester of pregnancy: a cutaneous electrogastrographic study. AB - Recently, it has been shown that changes in gastric electrical rhythm can be connected with clinical syndromes characterized by nausea and vomiting, among these the nausea of pregnancy. We studied gastric electrical activity during the first trimester of pregnancy in nine women with nausea and vomiting (study group) by means of cutaneous electrogastrography. Recordings were made before and after a standardized meal in the 6th-8th wk of gestation, and 2 months after voluntary interruption of pregnancy (VIP). The control group consisted of eight pregnant women without a history of nausea and vomiting. In the women in the study group there was more unstable cutaneous electrogastrographic (EGGc) activity and a reduced increase in postprandial power during pregnancy than after VIP, when a normal pattern with regular 3-cpm EGGc waves was reestablished. The coefficient of variation of gastric frequency during pregnancy was significantly higher than after VIP (p less than 0.01), whereas the postprandial to preprandial power ratio was lower (p less than 0.01). During the recording sessions, none of the subjects had clear episodes of tachygastria or bradygastria, and none of them had nausea, vomiting, or epigastric discomfort. Comparison of the EGGc data for the pregnant women in the study and control groups revealed a similar pattern of gastric electrical activity in the two, the only exception being the power ratio, which was lower in the study group (p less than 0.01). We conclude that pregnant women without symptoms of nausea and vomiting at the time of EGG recordings have normal 3-cpm myoelectrical activity, and that EGGc activity is more unstable and less responsive to the ingestion of food during pregnancy than after VIP. Furthermore, in pregnant women with a history of nausea and vomiting, EGGc activity is less responsive to the ingestion of food than it is in symptom-free pregnant women. PMID- 1590305 TI - Acute pancreatitis as a common complication of 2',3'-dideoxyinosine therapy in the acquired immunodeficiency syndrome. AB - Acute pancreatitis is observed in patients with the acquired immunodeficiency syndrome (AIDS) (4-22%), and is reported with increasing frequency as a complication of therapy in human immunodeficiency virus-spectrum disease. The cause is multifactorial (virus, neoplasm, drugs), and the natural history generally mild and uncomplicated. 2',3'-Dideoxyinosine (ddI) is an experimental antiretroviral agent implicated as a cause of acute pancreatitis in a small number (0.9-2%) of patients. To better define this relationship, we conducted a retrospective analysis of a prospective clinical trial involving 51 homosexual males with AIDS treated with ddI (10-12 mg/kg/day) and reported on the incidence and natural history of pancreatitis. Clinical pancreatitis (symptoms, elevated serum amylase, and lipase and, in most cases, abnormal radiographic studies of the pancreas) was observed in 12 patients (23.5%). Asymptomatic elevations of amylase and lipase were identified in 10 additional patients (39.2%). The onset of pancreatitis was consistently delayed in both groups (overall mean 14.1 +/- 1.2 wk, 98% confidence interval). Ten of 12 symptomatic patients required hospitalization (mean length of stay, 9.4 days); two of 12 progressed to fulminant pancreatitis and died. Two patients with asymptomatic pancreatitis which occurred after starting ddI were rechallenged; severe symptomatic pancreatitis developed shortly after drug reinstitution. In each case, complete recovery followed discontinuation of the drug. We conclude that 1) The incidence (62.7%) and severity of pancreatitis in patients with AIDS receiving ddI therapy are significantly greater than expected, 2) the onset is predictably delayed about 14 wk, 3) ddI should be added to the list of drugs that cause acute pancreatitis, and 4) careful sequential monitoring of pancreatic function and early identification of potential "risk factors" for pancreatitis in AIDS patients treated with ddI may be essential in avoiding this serious complication. PMID- 1590306 TI - Influence of a prior porta-systemic shunt on outcome after liver transplantation. PMID- 1590307 TI - Portohepatic pressures, hepatic function, and blood gases in the combination of nitroglycerin and vasopressin: search for additive effects in cirrhotic portal hypertension. AB - We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia. PMID- 1590308 TI - Percutaneous endoscopic gastrostomy with jejunal extension: a new technique. AB - Percutaneous endoscopic gastrostomies (PEG) with jejunal extensions are placed in patients at risk for aspiration of gastric contents. Current methods used are difficult and often ineffective in preventing aspiration, and frequently result in substantial morbidity and mortality. In this study, a new method of jejunal extension from a PEG was evaluated with regard to efficacy and prevention of aspiration of gastric contents while providing adequate enteral nutrition. Twelve patients with recent aspiration pneumonitis underwent PEG placement with a jejunal extension by this new method. The technique was accomplished rapidly and without difficulty in an average time of 26.2 min (range 17-31 min). In all instances, the jejunal extension remained functional for the first 8 wk after placement, and there were no instances of aspiration of gastric contents while nutritional requirements were met. None of the patients died from complications of the procedure. The method described was effective in preventing aspiration of gastric contents, was easily performed, and was associated with minimal complications. PMID- 1590310 TI - Seasonal pattern in the incidence of bleeding caused by peptic ulcer in Israel. AB - We have reviewed all endoscopies performed in our hospital between 1977 and 1986. During that period, 1337 endoscopies were performed to identify bleeding from peptic ulcers. Excluded were cases in which a predisposing factor was found, such as the use of ulcerogenic drugs. Also excluded were chronic or critically ill patients. The remaining 540 cases were reviewed. In 447 of those cases, the bleeding lesion was a duodenal ulcer, whereas, in 93 cases, a gastric ulcer was found (a ratio of 5:1). The seasonal variation in the incidence of bleeding from peptic ulcers was evaluated. We found a significant difference in bleeding in the cold and hot seasons, the incidence being significantly greater during the cold season (November until February). A similar pattern was found for bleeding from both duodenal and gastric ulcers. PMID- 1590309 TI - Blastocystis hominis in hospital employees. AB - Several reports have appeared that either support or deny the importance of the protozoan Blastocystis hominis as an intestinal pathogen in humans. In this report, we describe the clinical characteristics of B. hominis and its response to therapy in hospital employees found to have the parasite on routine screening of stools. During the study, 49 patients with B. hominis were identified, and 413 stools were examined from these patients. Twenty-nine patients were asymptomatic (59%), and 20 had symptoms of bloating, flatulence, soft/loose stools, or constipation. Of these 20 patients, 10 had symptoms that correlated with the presence or absence of B. hominis, four had symptoms that were independent of B. homonis, and six had other intestinal parasites that could account for their symptoms. Nineteen percent of patients without treatment had eradication of B. hominis from stool on follow-up examination. Metronidazole did not increase this rate. Iodoquinol treatment eradicated the organism in 41% of patients (p less than 0.05), and resulted in the reduction or eradication of the parasite in 62%, as determined by follow-up examination. PMID- 1590311 TI - Polyamine metabolism in colonic mucosa from patients with ulcerative colitis. AB - Polyamine metabolism in mucosa both from patients in the active or remission stage of ulcerative colitis (UC) and from healthy controls was studied. In the active stage of UC, mucosal spermidine concentration was higher than in remission or in the controls, but the activities of ornithine decarboxylase and S adenosylmethionine decarboxylase, rate-limiting enzymes of polyamine biosynthesis, were lower. In the active stage of UC, the mucosal level of mRNA coding for ornithine decarboxylase was lower than in the remission stage of UC or in the controls. The activity of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme of polyamine degradation, was higher in the active stage of UC than in the remission stage of UC or in the controls. However, it seemed that this activity did not reflect the increase in the spermidine concentration. The results showed that the spermidine increase in the active stage of UC was not due to changes in the synthesis or degradation of polyamines; the increase may have been due to increased exogenous spermidine uptake. PMID- 1590312 TI - Oxyntic and antral gastritis in the People's Republic of China: diagnosis and relationship to Helicobacter pylori. AB - This study investigates the relationship between gastritis and Helicobacter pylori infection in the Chinese population. Particular focus was placed upon the grading of gastritis, using the recently developed "Sydney system." Five diagnostic procedures were used to establish H. pylori status, all of which were found to be highly sensitive and specific. Histological chronic gastritis was reported in 93/108 (86.1%) of the patients examined, H. pylori infection being present in 73/93 (78.5%), and in no patient with histologically normal mucosae. There was a relatively high incidence of idiopathic antral gastritis within the gastritic population, 20/93 (21.5%). In the H. pylori-positive group, 10/73 (13.7%) had pangastritis, 57/73 (78.1%) had pangastritis-antrum-predominant, and 6/73 (8.2%) had antral-only gastritis. The level of activity was significantly higher in the antrum; however, the distribution of bacteria between the antrum and body was not significantly different. There is a need for additional studies examining the specific topographical relationship between H. pylori, the histology, and gastroduodenal disease. PMID- 1590313 TI - Esophageal squamous carcinoma in five patients with Barrett's esophagus. AB - Adenocarcinoma of the esophagus is a well-known complication of Barrett's esophagus. This report describes five patients (three men and two women) with Barrett's esophagus and squamous carcinoma of the esophagus. All patients had hiatal hernia, and three had a history of tobacco and alcohol use. The tumors were located in the Barrett's mucosa in one case, at the squamocolumnar junction in two cases, and in the squamous-lined mucosa above the Barrett's mucosa in two cases. One patient also had focal adenocarcinoma associated with the squamous carcinoma of the esophagus. Review of the literature identified 11 previously reported cases. Occurrence of esophageal squamous carcinoma in Barrett's esophagus patients suggests a possible relationship between these two conditions, and the need for a careful evaluation of the squamous esophageal mucosa and the squamocolumnar junction at the time of endoscopy. PMID- 1590315 TI - Surgical diseases of the falciform ligament. AB - Surgical lesions of the falciform ligament are rare. Clinically, they present most often as a cystic abdominal mass, and less often as an abscess. Two cases of falciform ligament lesions are reported. The literature, histology, anatomy, clinical manifestations, and surgical management are detailed. Computerized axial tomography (CAT scan) is an essential tool in arriving at a correct preoperative diagnosis. Complete excision of the lesion is curative. PMID- 1590314 TI - Evidence for colonic conservation of malabsorbed carbohydrate in short bowel syndrome. AB - The purpose of this study was to determine whether energy from malabsorbed carbohydrate could be conserved through colonic fermentation in short bowel syndrome. Seven patients with short bowel anastomosed to the remaining colon and five patients with short bowel without a colon were selected from the home total parenteral nutrition (TPN) program. Six normal volunteers also were studied. After an overnight fast, subjects consumed a 50-g carbohydrate bread meal and were studied hourly over the next 6 h. Carbohydrate malabsorption, estimated by lactulose breath hydrogen testing, was 48 +/- 13% in short bowel patients. After the bread meal, breath hydrogen was higher in short bowels with colons (69 +/- 20 ppm) than in either short bowels without colons (11 +/- 7 ppm) or normal subjects (10 +/- 3 ppm) (p less than 0.01). Blood acetate levels also were higher in short bowels with colons than in those without colons, reaching a peak of 167 +/- 27 mumol/L at 4 h (p less than 0.05). We conclude that in patients with a short bowel and a colon, malabsorbed carbohydrate is fermented and there is a rise in blood acetate, suggesting that the colon has a role in salvaging malabsorbed carbohydrate as a source of energy through carbohydrate fermentation. PMID- 1590316 TI - Pneumocystis colitis in a patient with the acquired immunodeficiency syndrome. AB - We report a case of colonic pneumocystosis in a human immunodeficiency virus (HIV)-positive homosexual male who presented with fever and diarrhea. Stool cultures for bacterial pathogens and examinations for ova and parasites were negative. The diagnosis was made by colonoscopic biopsy which revealed Pneumocystis carinii organisms in the lamina propria of the cecum, descending colon, and sigmoid colon. The patient subsequently developed pulmonary and ocular abnormalities consistent with P. carinii involvement of these organs. The diarrhea and other manifestations resolved with antipneumocystis therapy. Many sites of extrapulmonary pneumocystosis have been reported, but we believe this is the first report of colonic P. carinii found in the evaluation of persistent diarrhea in a patient with the acquired immunodeficiency syndrome. PMID- 1590317 TI - Endoscopic ultrasonography and endoscopically guided needle aspiration for the diagnosis of upper gastrointestinal tract foregut cysts. PMID- 1590318 TI - Multiple carcinoid tumors of the stomach with hypergastrinemia. AB - A 42-yr-old woman presented with multiple carcinoid tumors in her stomach and a markedly elevated serum gastrin level. Total gastrectomy was performed, and 22 small carcinoid tumors were found in the gastric fundus and body. A high serum gastrin level was revealed in the gastric drainage veins; still more gastrin was detected in the carcinoid tumors by the immunohistochemical method, and many secretory granules were found in the tumor cells with an electron microscope. The fundic gland showed marked atrophy, and there was some conglobation of endocrine cells (ECL cells). This case suggests a hypothetic sequence of anacidity due to atrophic gastritis----hypergastrinemia----proliferation of ECL cells----multiple carcinoids. A search of the Japanese literature revealed that 26 cases of multiple carcinoid tumors in the stomach have been reported so far, and most of them support this hypothesis. PMID- 1590319 TI - Steatohepatitis and fatal hepatic failure after biliopancreatic diversion. AB - Steatohepatitis and hepatic failure are well known complications of jejunoileal bypass, an operation that has been abandoned as a treatment for severe obesity because of its potential for adverse metabolic consequences. Biliopancreatic diversion is a novel operation designed to avoid the harmful effects of jejunoileal bypass. Although it has not gained wide acceptance, this procedure is being advocated by some surgeons as a safe and effective treatment for severe obesity. Published reports indicate that liver histology generally remains stable or improves after biliopancreatic diversion. We present a patient who developed steatohepatitis and subsequently died in hepatic failure after this operation. Severe liver disease should be added to the list of complications that may follow biliopancreatic diversion. PMID- 1590321 TI - Hepatopulmonary fistula: treatment with biliary metallic endoprosthesis. AB - Hepatopulmonary communication, most commonly in the form of bronchobiliary fistula, is an unusual lesion that can occasionally close spontaneously, but usually requires surgical therapy. The usual treatment has been a combined thoracoabdominal approach with correction of the fistulous tract or an abdominal approach to correct the causative bile duct obstruction. Both endoscopic and percutaneous therapy of the biliary ductal system have been described as forms of treatment. We present a case of hepatopulmonary fistula in a patient with bilioptysis, treated with percutaneous biliary metallic endoprosthesis. To our knowledge, this is the first reported case in which metallic stents were used to treat a hepatopulmonary fistula. PMID- 1590320 TI - Protein-losing enteropathy with collagenous colitis. AB - Collagenous colitis is a distinct cause of chronic watery diarrhea characterized by abnormal deposition of collagen in the subepithelial region of the colonic mucosa. Typically, laboratory tests of blood, urine, and stool are normal. A few patients have laboratory evidence of small bowel dysfunction and malabsorption, but excessive enteric protein loss is not a commonly recognized manifestation of collagenous colitis. We report a 62-yr-old woman who had collagenous colitis associated with a marked protein-losing enteropathy in the absence of obvious small intestinal disease or colonic ulceration. Biopsies of endoscopically normal appearing colonic mucosa should be performed in patients with protein-losing enteropathy in whom no cause is apparent after initial evaluation. PMID- 1590322 TI - Mucocele of the appendix: computed tomographic, endoscopic, and pathologic correlation. AB - Mucoceles of the appendix are a rare group of lesions thought to occur as a sequelae of luminal obstruction as well as certain benign and malignant neoplasms of the appendix. Early, preoperative diagnosis is rare. We report a case of an appendiceal mucocele in which the diagnosis was suggested by computed tomographic imaging and colonoscopy, and confirmed at surgery. Radiologic, endoscopic, and pathologic correlations of this rare entity are discussed. PMID- 1590323 TI - Foregut ischemia and odynophagia in a patient with a type III aortic dissection. AB - We report a case of ischemia of the distal esophagus with secondary odynophagia that occurred as a result of a type III aortic dissection. A 56-yr-old hypertensive male presented with acute chest pain radiating to his back. A dissection of the descending aorta was found to begin just distal to the left subclavian artery and end in the region of the iliac arteries. The patient was treated medically and remained stable, but then developed odynophagia to solids. Upper endoscopy showed erythematous friable esophageal mucosa, and biopsies were consistent with ischemia. Aortography and barium fluoroscopy provided further evidence of foregut ischemia. The patient recovered on oral omeprazole with no residual symptoms. Ischemic compromise of the esophagus secondary to aortic dissection has not been previously described, nor have the associated endoscopic findings. Knowledge of this rare condition may help in the recognition and management of esophageal mucosal ischemia. PMID- 1590324 TI - Gastric bezoar caused by lecithin: an unusual complication of health faddism. AB - We discovered an unusual bezoar in a previously healthy man who had been ingesting large amounts of a vegetable-derived oil touted to contain lecithin, which he purchased from health food stores in the belief that it had beneficial effects in lowering cholesterol levels and improving memory. The large intragastric mass, composed of fatty acids and lecithin, led to considerable morbidity, including abdominal pain, early satiety, and significant weight loss, and required surgical removal. PMID- 1590325 TI - Alcohol hepatotoxicity: a genotypic predisposition? PMID- 1590326 TI - Pancreas divisum and acute pancreatitis: romancing the stone? PMID- 1590327 TI - Second look surgery--a shell game? PMID- 1590328 TI - Variations of the pancreatic ducts as a cause of chronic alcoholic pancreatitis; ansa pancreatica. PMID- 1590329 TI - Perspective as to pathogenesis and management of hyperemesis in pregnancy. PMID- 1590330 TI - Metronidazole resistance among Helicobacter pylori strains in Malaysia. PMID- 1590331 TI - Acute colonic ulceration proximal to obstructing colon neoplasms. PMID- 1590332 TI - Immune thrombocytopenia after alpha-interferon therapy in a patient with chronic hepatitis C. PMID- 1590333 TI - Sigmoid-biliary fistula: a rare complication of colonic diverticulitis. PMID- 1590334 TI - Lost and found. PMID- 1590335 TI - Ganciclovir: handle with care. PMID- 1590336 TI - Surviving a deposition. PMID- 1590337 TI - A smoking run. PMID- 1590338 TI - Lighten up! PMID- 1590339 TI - Lighten up! PMID- 1590340 TI - The aides debate. PMID- 1590341 TI - TB plus HIV spells trouble. PMID- 1590342 TI - Low-tech, high-touch perfusion assessment. PMID- 1590343 TI - A guideline for the nation: managing acute pain. PMID- 1590344 TI - Codes for a code. PMID- 1590345 TI - Nurses on stamps: a distinguished history. PMID- 1590346 TI - How nurses redefine reality. PMID- 1590347 TI - The richness of oncology nursing. PMID- 1590348 TI - How do you use shallow-suction technique in children? PMID- 1590349 TI - Wound measurements: some tools of the trade. PMID- 1590350 TI - As demand for HIV insurance grows, insurers move to market new policies. PMID- 1590351 TI - Precontact mammalian sperm-egg communication and role in fertilization. AB - In creatures with external fertilization, e.g., metazoa, it is well established that there is precontact sperm-egg communication in the form of chemotaxis. An intriguing question is whether also in mammals, where fertilization is internal and the need for precontact sperm-egg communication is not self-evident, such a process occurs and what its physiological significance may be. Here we review the evidence related to such a process in mammals, evidence which suggests that sperm attraction to the ovulated egg may indeed occur. On the basis of the available data we propose a hypothesis, according to which a sperm population is heterogeneous with respect to its physiological state; some spermatozoa are at a physiological state ready for fertilizing an egg, while others are premature or overmature. According to the hypothesis this is a dynamic state; the population of fertilizing spermatozoa gradually loses its potency and, at the same time, other spermatozoa mature and acquire fertilizing ability. After ovulation, only the fertilizing spermatozoa are attracted to the egg, while the rest are either repelled or inhibited and thus prevented from reaching the egg. The potential significance of sperm-egg communication is discussed. PMID- 1590352 TI - Alterations in lipolytic activity at hepatic subcellular sites of fed and fasted rats. AB - This study investigates the relationship between the nutritional state of rats and lipid metabolism in distinct hepatic intracellular sites. Hepatic uptake of both protein and triacylglycerol (TG) moieties of injected very low-density lipoprotein (VLDL) is increased in fasted rats compared with fed controls. The VLDL-TG hydrolysis rate is increased in the plasma of fasted rats. This is shown by a higher ratio of labeled free fatty acid (FFA) to TG (FFA/TG). In both fed and fasted rats, a much greater increase of the labeled FFA/TG ratio in endosomes, compared with that in plasma, shows that further TG hydrolysis occurs in prelysosomal compartments. However, in fasted rats, this increase (18-fold) is much less than that in fed rats (69-fold). This observation is supported by the finding of significantly lower TG-lipase activity at pH 5, 7, and 8.6 in the endosomes of fasted rats. In contrast, during fasting, TG-lipase activity in whole liver homogenate and in isolated lysosomes is increased at pH 5. These observations suggest that after feeding there is a shift in intracellular lipolytic activity from lysosomes to prelysosomal organelles. PMID- 1590353 TI - Water and nonelectrolyte permeabilities of apical membranes of toad urinary bladder granular cells. AB - Certain types of epithelial cells such as those lining the toad urinary bladder have been classified as "tight" because their apical membranes exhibit low permeabilities to water, ions, and small nonelectrolytes. However, the permeability properties and structural features of these specialized apical membranes remain unclear because these membranes have never been purified. To isolate toad bladder granular cell apical membranes, we derivatized the bladder apical surface with the membrane-impermeant bifunctional reagent N hydroxysulfosuccinimydyl-S,S-biotin (NHS-SS-biotin). After cell disruption, these derivatized apical membranes were purified using streptavidin-coated magnetic beads in a magnetic field. With the use of lactoperoxidase-mediated radioiodination as a marker for apical membrane, this preparative procedure purified apical membrane 48- or 72-fold as compared with homogenate. Thin section electron microscopy revealed unilamellar vesicles with some nonvesiculated membranes, while fragments of organelles such as mitochondria were absent. Water and nonelectrolyte permeabilities of purified apical membrane vesicles were similar to those obtained in intact bladders in the absence of antidiuretic hormone stimulation. The results demonstrate that isolated apical vesicles do not contain water channels and confirm the applicability of Overton's rule to the apical membrane of the toad urinary bladder. The technique has general applicability to isolation of other plasma membranes, and the apical membranes obtained are suitable for structural analysis. PMID- 1590354 TI - Localization and differential expression of two isoforms of the tight junction protein ZO-1. AB - ZO-1 is a peripheral membrane protein of approximately 225 kDa located on the cytoplasmic side of all tight junctions. ZO-1 cDNA sequencing disclosed the presence of a 240-bp sequence in only some of the ZO-1 cDNAs studied. This 240-bp region encoded an inframe insertion of 80 amino acids, named motif-alpha. Expression of the predicted transcripts in normal rat and human tissues and in human epithelial cell lines (Caco-2, T84, Hep G2) was shown by reverse transcription of RNA and then DNA amplification. Immunoblot analysis showed both protein isoforms were present; however, in different cell lines, their amounts differed markedly relative to each other. Immunolocalization at light and ultrastructural levels, using antibodies generated against motif-alpha or shared sequences flanking it, indicated both forms localized indistinguishably to tight junctions. These observations demonstrate the existence and variable expression of ZO-1 isoforms and raise the question whether these isoforms contribute to tight junction diversity in different epithelia. PMID- 1590355 TI - Discoordinate hormonal and ontogenetic regulation of four rat serpin genes. AB - To understand the roles of four highly homologous rat hepatic serine protease inhibitor genes (Spi 2.1, Spi 2.2, Spi 2.3, and alpha 1-antitrypsin), we measured the hepatic content of their specific mRNAs under several physiological conditions. Spi 2.1 and 2.3 mRNAs, which are regulated by growth hormone, paralleled serum growth hormone levels developmentally. Only Spi 2.1 mRNA decreased with starvation, while Spi 2.2, 2.3, and alpha 1-antitrypsin mRNAs did not change. Despite the close homology of the Spi genes to mouse contrapsin, which is regulated by testosterone, none of the serine protease inhibitor mRNAs examined here was dependent on androgens for expression. Spi 2.2 mRNA displayed a unique ontogenetic regulation, with a rise in hepatic content at day 19 to levels five times that of any other age group. These studies confirm the importance of growth hormone in the regulation of Spi 2.1 and 2.3 mRNAs and suggest that Spi 2.2 mRNA may be regulated by metabolic alterations occurring in the weaning period. PMID- 1590356 TI - A discrete Na-Ca exchange-dependent Ca compartment in rat ventricular cells: exchange and localization. AB - Application of a new rapid perfusion (up to 4.8 ml/s) technique to 45Ca-labeled ventricular cells from adult rat heart has defined a discrete intracellular calcium (Ca) compartment with the following characteristics: 1) its exchange is absolutely dependent on operation of the Na-Ca exchanger, i.e., its isotopic content remains constant during washout in the absence of Na and Ca and is released only upon addition of Na and Ca to the perfusate. 2) At an extracellular Ca concentration of 1.0 mM it contains 350 mumol/kg dry wt cells and exchanges with half time of 650 ms. Ca flux from the compartment is 385 mumol.kg dry wt-1.s 1 or 20% of the total nonperfusion limited flux from the cells. 3) Its content is decreased 19% by 10 mM caffeine but not diminished by exposure of the cells to 10(-6) M ryanodine and not accessible to lanthanum (La) displacement. 4) Only limited exchange occurs when only Na or Ca is present and exchange is virtually eliminated by substitution of extracellular Li for extracellular Na. 5) Replacement of Na and Ca to the perfusate after various periods of removal produces no contraction (despite immediate Ca release from the cell). The results define a discrete intracellular Ca compartment which exchanges only via the Na-Ca exchanger. It is not La accessible, not in the ryanodine- or caffeine-sensitive portions of the sarcoplasmic reticulum, not in the mitochondria nor at the myofilaments, but may reside at inner sarcolemmal leaflet binding sites. PMID- 1590357 TI - Verapamil blocks basolateral K+ channels in the larval frog skin. AB - The short-circuit current (Isc) across isolated skin from larval frogs (Rana catesbeiana) was measured when the tissue was bathed with Na2SO4 Ringer solution on the serosal side and with a Ringer solution containing K+ as the primary cation on the mucosal side. When 150 U/ml nystatin was added to the mucosal solution, the Isc increased from 1.4 +/- 0.1 to 35.4 +/- 4.8 microA/cm2. When verapamil was added to the mucosal and serosal Ringer solutions in concentrations between 2.5 and 80 microM, Isc was inhibited in a stepwise manner. At 80 microM, Isc was reduced by 75.3% to 8.74 +/- 1.14 microA/cm2. Analysis of the inhibition of Isc with the direct linear plot method showed that the blockage of Isc could be described by pseudo-first-order kinetics with a Michaelis constant (Km) of 9.59 +/- 2.20 microM. Fluctuation analysis revealed a Lorentzian component in power spectra obtained from preparations treated with 10-80 microM verapamil. The corner frequency of these Lorentzian components increased in a linear manner over this range of verapamil concentrations. The Km calculated from the ratio of the dissociation and association rate constants (k10/k'01) was 39.5 microM. The single-channel currents (i) calculated from the fluctuation analysis parameters decreased significantly between verapamil concentrations of 10 and 80 microM. It appears that the inhibition of K+ channels in the basolateral membrane of this tissue has at least two components.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590358 TI - Chloride is required for fluid transport by the rabbit corneal endothelium. AB - The role of chloride in fluid transport of the rabbit corneal endothelium was examined by measuring changes in corneal thickness following ion substitutions or addition of ion transport inhibitors in media superfusing the isolated tissue. Normal fluid transport is indicated by maintenance of constant thickness in a fresh cornea or thinning (deturgescence) of a preswollen deepithelialized cornea to its initial thickness at approximately 40 microns/h. These patterns are seen when tissues are superfused with HCO(3-)-Ringer containing 114 mM Cl-. When Cl- was substituted with gluconate, glucuronate, or SO4(2-) fresh and preswollen corneas immediately thinned at greater than 150 microns/h to a value less than 300 microns and then began to swell at 30 microns/h to above their original thickness. Substitution of Cl- with NO3- or Br- had a negligible immediate thinning effect, but fresh corneas subsequently swelled and preswollen corneas failed to deturgesce fully. The rapid thinning (called a "downtransient") observed with gluconate, glucuronate, and SO4(2-) also occurred in these media when ion and fluid transport were completely inhibited with ouabain or stilbenes or by absence of HCO3-, indicating that the thinning results from osmotic gradients induced by ionic reflection coefficients different from that of Cl-. When the downstransient was avoided in deepithelialized corneas by preswelling with the same Cl(-)-free media on both sides of the cornea, corneas maintained a constant but swollen thickness in gluconate and in NO3- or Br- deturgesced slowly and incompletely; ouabain or stilbenes caused further swelling in all media. We conclude that absence of Cl- partially impairs fluid transport, most probably via its role in a Cl(-)-HCO3- exchanger which has been proposed in a recent model of endothelial fluid transport. PMID- 1590359 TI - Ethanol metabolism and inhibition of nucleoside uptake lead to increased extracellular adenosine in hepatocytes. AB - Recent evidence suggests that adenosine mediates many of the acute and chronic effects of ethanol in both cultured cells and whole animals. These adenosine mediated effects of ethanol result from ethanol-induced increases in extracellular adenosine. Acute exposure of primary cultures of rat hepatocytes to 12.5-200 mM ethanol increased extracellular adenosine concentrations by 20-35%. Pretreatment of hepatocytes with 100 microM 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, completely blocked ethanol-induced increases in extracellular adenosine at 12.5 and 25 mM ethanol. However, even in the presence of 4-methylpyrazole, ethanol at concentrations greater than 50 mM still increased extracellular adenosine concentrations. This increase appears to be due to ethanol inhibition of adenosine uptake via the nucleoside transporter (50% inhibitory concentration, 28 mM). After chronic treatment with 100 mM ethanol for 48 h, acute challenge with ethanol no longer inhibited adenosine uptake, i.e., the nucleoside transporter had become tolerant to ethanol. Moreover, in these chronically treated cells, ethanol-induced increases in extracellular adenosine were completely blocked by treatment with 4-methylpyrazole at all concentrations of ethanol. Taken together, these results suggest that increased extracellular adenosine in hepatocytes is dependent on both ethanol oxidation and inhibition of adenosine uptake via the nucleoside transporter. PMID- 1590360 TI - Active transport of dopamine in human placental brush-border membrane vesicles. AB - Brush-border membrane vesicles isolated from normal human term placentas were found to accumulate dopamine against a concentration gradient when an inwardly directed NaCl gradient was imposed across the membrane. The activity of the transport system was obligatorily dependent on Na+ as well as Cl-. Intravesicular H+ and intravesicular K+ stimulated the transport activity. The system possessed high affinity for dopamine and norepinephrine, with considerably lower affinity for serotonin. The stoichiometry of Na(+)-Cl(-)- dopamine was 1:1:1. The system was electrogenic because the NaCl-dependent dopamine uptake was stimulated by an inside-negative membrane potential, and this characteristic was observed in the presence and in the absence of intravesicular K+. Kinetic analysis revealed that the uptake was due to a carrier-mediated component plus a diffusion/binding component. The apparent Michaelis-Menten constant for dopamine for the carrier mediated component was 19 +/- 7 nM. The transport system was clearly distinct from the serotonin transporter. Analysis of the inhibition of dopamine uptake by various monoamine uptake inhibitors showed that the uptake occurred via a transport system that is similar to the neuronal norepinephrine transporter. PMID- 1590361 TI - ATP-sensitive potassium channel is essential to maintain basal coronary vascular tone in vivo. AB - Glibenclamide, a known selective inhibitor of ATP-sensitive potassium channels, was infused into the coronary vasculature of anesthetized dogs and of isolated perfused rabbit hearts to assess the role of this channel in the maintenance of basal coronary resistance. Infusion of glibenclamide at a concentration of 55-80 microM in the dogs resulted in a twofold steady-state increase in coronary resistance with resultant tissue ischemia. Infusion of 1 microM glibenclamide in the isolated hearts resulted in a 67% increase in coronary resistance with resultant tissue ischemia. The ischemic changes were reversible upon removal of the drug. These findings indicate that the ATP-sensitive K+ channel plays a significant role in the maintenance of basal coronary resistance in vivo. Higher concentrations of glibenclamide (80-100 microM) in the in vivo dog heart consistently gave rise to an oscillating pattern of coronary flow. These oscillations were either eliminated or decreased in amplitude and frequency by the infusion of 8-phenyltheophylline, a specific competitive inhibitor of adenosine receptors. 31P-nuclear magnetic resonance spectroscopy performed at the peaks and troughs of these oscillations revealed oscillation of the phosphorylation potential at the same frequency. Thus adenosine release caused by tissue ischemia appears to play a major role in creating the oscillating pattern of coronary blood flow, that occurs during the inhibition of ATP-sensitive K+ channels by glibenclamide. PMID- 1590362 TI - Kinetics of force generation and phosphate release in skinned rabbit soleus muscle fibers. AB - The kinetics of the force generating and Pi release steps of the actomyosin adenosinetriphosphatase (ATPase) cycle have been compared in Ca(2+)-activated skinned fibers of rabbit soleus (slow twitch) and psoas (fast twitch) muscle. Pi was rapidly photogenerated within the fiber lattice by laser flash photolysis of caged Pi [1-(2-nitro)phenylethyl phosphate]. Pi reduces isometric tension in the steady state but is less effective in slow-twitch muscle than in fast-twitch muscle (e.g., 14 mM Pi reduces tension by 29 +/- 4.6% in slow and by 47 +/- 5.3% in fast). The tension response to a sudden increase in Pi concentration in slow twitch muscle has four phases, but as in fast-twitch muscle, only phase II (an exponential decline in force) appears to be caused by Pi binding to cross bridges, whereas the other three phases are probably indirect effects caused by caged Pi photolysis. The amplitude of phase II is consistent with the steady state reduction in force by Pi. The rate of phase II (kappa Pi) is 3.9 +/- 0.33 s 1 at 20 degrees C and 0.28 +/- 0.02 s-1 at 10 degrees C (1 mM Pi). kappa Pi is thus 33 times slower in slow-twitch muscle than in fast at 20 degrees C and 84 times slower at 10 degrees C. In contrast to fast-twitch muscle, in slow muscle kappa Pi is sufficiently slow to partially limit the ATPase turnover rate. PMID- 1590363 TI - Developmental increases in the inwardly rectifying potassium current of rat ventricular myocytes. AB - The neonatal rat ventricular action potential has a shape similar to that of most adult mammals. However, shortly after birth, the action potential shortens to a spike-like configuration. The contribution of changes in repolarizing currents to the shortening is unclear. Thus the inwardly rectifying potassium current (IK1) was measured in heart cells from rats of varying ages using patch-clamp techniques. In freshly isolated cells, whole cell IK1 currents increased greatly between ages 3 and 9-13 days and remained constant thereafter. In culture, IK1 disappeared preferentially in older cells, obscuring the developmental increase. Age-dependent differences in single-channel activity were also observed. Adult cells had IK1 channels consisting of two populations (30 and 42 pS), whereas neonatal cells exhibited only the lower conductance channel. The appearance of the 42-pS channel may contribute a part of the developmental increase in IK1. It was concluded that IK1 increases during postnatal development of the rat ventricle and that this increase may contribute to the postnatal shortening of the rat ventricular action potential. PMID- 1590364 TI - 23Na-NMR study of cation cotransport in human red blood cells. AB - Na(+)-K+ cotransport in human erythrocytes from healthy subjects has been studied by means of 23Na-nuclear magnetic resonance (NMR) in the presence of the anionic paramagnetic shift reagent dysprosium (III) tripolyphosphate [Dy(PPP)2(7-)]. The intra- and extracellular 23Na-NMR signals were well separated, giving values of 6 +/- 1 mM for internal sodium concentration. Determination of the furosemide sensitive Na+ efflux, in the presence of ouabain, was obtained by correlating the chemical shift variation of the external signal with changes in external Na+ concentration. For this purpose, calibration curves were generated. The values of the maximum efflux velocity (Vmax; 0.29-1 mmol.h-1.l cells-1) measured in 10 healthy adult male subjects were found to be within the range of values obtained by other authors. The NMR method proposed for the study of Na(+)-K+ cotransport is relatively simple and allows quick evaluation of cotransport Vmax values for a number of samples, being a good candidate for the study of this transport mechanism in the presence of different pathologies. PMID- 1590365 TI - Goblet cell degranulation in isolated canine tracheal epithelium: response to exogenous ATP, ADP, and adenosine. AB - Mucin secretion by goblet cells was determined by quantifying degranulation events (DE) in isolated, superficial epithelium from canine trachea. The epithelium was isolated and explanted to a novel transparent, permeable support, and the goblet cells were visualized by video microscopy. Baseline degranulation events were quantified at 0.05 DE/min. Luminal ATP (10(-4) M, n = 10) stimulated a biphasic secretory response; a burst, maximum rate = 87.9 +/- 25.3, was followed by a plateau, rate = 1.9 +/- 0.3 DE/min. Serosal ATP elicited a complex set of responses: 9 cells failed to respond, 13 exhibited a trivial response, and 31 responded vigorously but with highly variable patterns of degranulation. Nonhydrolyzable 5'-adenylylimidodiphosphate caused degranulation from both sides of the epithelium. Luminal ADP and adenosine were ineffective. Serosal ADP and adenosine elicited a range of responses that was similar in diversity and magnitude to the ATP response. Our conclusions were as follows: 1) goblet cells in the superficial epithelium of the airway can be studied at the single-cell level in explants; 2) nucleotides stimulate goblet cells to secrete mucin; and 3) the goblet cell expresses different nucleotide receptors on its apical and basolateral membranes. PMID- 1590366 TI - Calibration of ion-selective microelectrodes. AB - Measurements of intracellular and extracellular ion activities with ion-selective microelectrodes generally involve calibration of the electrodes in solutions of known composition and fitting of the calibration data with a theoretical expression. The Nicolsky equation is frequently used to describe the variation of electrode potential with primary ion activity in the presence of a constant amount of interference. In this report, we review the estimation of primary ion activities in calibration solutions and discuss the practical use of the Nicolsky equation. We describe a specialized computer program, developed in this laboratory, for routine input and editing of calibration data, fitting of data with the Nicolsky equation, and calculation of experimental ion activities from the fitted curve. Earlier versions of this program have proven helpful in several investigations in this and in other laboratories. PMID- 1590367 TI - Age-related differences in basal and calcium-stimulated plasma calcitonin levels in female rats. AB - The effects of aging on calcitonin (CT) secretion in female rats were investigated. Old (24 mo) at constant diestrus status and young (2 mo) at diestrus status rats were either ovariectomized (Ovx) or left intact as controls. Ovx rats were injected subcutaneously with estradiol benzoate (25 micrograms/kg body wt) or sesame oil one time per day for 3 days. All rats were infused with CaCl2 (10 mg/ml) at a rate of 2 ml/h for 30 min via a jugular catheter connected to a peristaltic pump. Blood samples (0.5 ml each) were collected at 0, 30, 60, and 120 min. The basal and post-CaCl2 levels of plasma Ca measured with radioimmunoassay were significantly higher (P less than 0.05-0.01) in old than in young female rats. The pre- and post-CaCl2 levels of plasma Ca and CT in young rats were not altered by Ovx or estradiol replacement. In old rats, Ovx caused a higher (P less than 0.01) level in plasma CT at 0 and 30 min after CaCl2 infusion. Both basal and stimulated levels of plasma CT were higher (P less than 0.01) in old Ovx than in young Ovx rats. These results demonstrated that 1) the increase of plasma CT in response to Ca challenge was greater in old than in young female rats, 2) the influence of estradiol and ovarian function on plasma CT concentration increases as a function of age, and 3) estradiol reduced the plasma CT in response to hypercalcemia in old Ovx rats. The sensitivity of the target tissue of young rats may be lower in response to the modulation of estrogen during hypercalcemia without compromising the secretion and hypocalcemic effect of CT in young rats. All suggested an age-related relationship between estrogen and CT secretion in minute-to-minute regulation during Ca infusion in rats. PMID- 1590368 TI - Insulin receptor binding and kinase activity in liver and skeletal muscles of lactating goats. AB - Lactation in goats has been shown to modify in vivo insulin action. [Debras, E., J. Grizard, E. Aina, S. Tesseraud, C. Champredon, and M. Arnal. Am. J. Physiol. 256 (Endocrinol. Metab. 19): E295-E302, 1989]. To further elucidate the mechanism of insulin action, we studied insulin binding and insulin receptor tyrosine kinase activity in solubilized and partially purified receptor preparations from liver and skeletal muscles (longissimus dorsi, tensor fascia lata, diaphragm, and masseter) from lactating and nonlactating goats. Lactation did not alter insulin receptors in the various skeletal muscles and had a minor influence on liver receptors (where only a 20% increase in receptor number was visible, P less than 0.05). Insulin-stimulated autophosphorylation and the kinase activity against polyglutamyltyrosine (4:1) were not significantly modified in skeletal muscle receptor preparations from lactating goats when compared with nonlactating animals. They tended to decrease in liver preparations, but not significantly. Thus the changes in insulin action in vivo during lactation in goats were not related to modifications in insulin kinase activity but were probably localized at a postreceptor level. PMID- 1590369 TI - Glucoregulation during rest and exercise in depancreatized dogs: role of the acute presence of insulin. AB - To determine the effects of the presence of insulin in poorly controlled diabetes, depancreatized (PX) dogs (n = 5) were studied during rest and 150 min of exercise in paired experiments in which saline alone was infused (IDEF) and in which insulin was replaced intraportally (200 microU.kg-1.min-1) with glucose clamped at the levels in IDEF (IR+G). PX dogs (n = 4) were also studied with insulin, but glucose was allowed to fall (IR). Insulin was not detectable, 6 +/- 1 and 6 +/- 2 microU/ml in IDEF, IR+G, and IR. Plasma glucose was 470 +/- 47, 480 +/- 48, and 372 +/- 35 mg/dl at rest in IDEF, IR+G, and IR, respectively. Levels were unchanged with exercise in IDEF and IR+G, but fell by 139 +/- 13 mg/dl in IR. Basal glucose rate of appearance (Ra) was 7.0 +/- 0.9, 1.3 +/- 1.1, and 6.0 +/- 0.7 mg.kg-1.min-1 in IDEF, IR+G, and IR, respectively. Exercise elicited a rise in Ra in only IDEF. The rises in Rd and metabolic clearance rate in IDEF were reduced (delta 2.6 +/- 0.7 and delta 0.8 +/- 0.3 ml.kg-1.min-1 at 150 min) compared with IR+G (delta 5.3 +/- 1.9 and delta 1.7 +/- 0.2 ml.kg-1.min-1 at 150 min) and IR (delta 3.7 +/- 1.2 and delta 2.4 +/- 0.8 ml.kg-1.min-1). The insulin sensitivity of glucose utilization (Rd) was elevated by approximately 75% at 150 min. Basal glycerol was similar in IDEF and IR but was reduced by approximately 70% in IR+G. Glycerol rose similarly with exercise in IDEF and IR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590370 TI - Trace element movement and oxidative stress in skeletal muscle atrophied by immobilization. AB - The movements of trace elements and the level of oxidative stress in the soleus, a typical slow red muscle which, atrophied by immobilization, were investigated in designated intervals. Male Wistar rats (14 wk old) whose one ankle joints were immobilized in the extended position were killed after 4, 8, and 12 days. Fe, Zn, Mn, and Cu concentrations and the levels of thiobarbituric acid-reactive substance (TBARS) and glutathione were measured. The rate of atrophy increased rapidly until the 8th day and slowly after that. In whole muscle, Fe concentration kept increasing, and Zn and Mn increased temporarily. Their subcellular distributions also changed; especially, the Fe level of the microsomal fraction kept increasing and reached threefold at 12 days. Increased TBARS and glutathione disulfide and decreased total glutathione indicated the increased oxidative stress in atrophy, which might result from an increased Fe level, especially that of the microsomal fraction. Vitamin E injection lessened the rate of atrophy, which showed that oxidative stress accelerated muscle atrophy. This might be mediated by increased intracellular Ca. Also metallothionein was induced in muscle atrophy. PMID- 1590371 TI - Analysis of PTHRP binding and signal transduction mechanisms in benign and malignant squamous cells. AB - We have explored a potential autocrine role for parathyroid hormone-related protein (PTHRP) in malignant squamous carcinoma cells (SqCC) and their nonmalignant counterpart, human epidermal keratinocytes (HK). Specific binding of Tyr36 human PTHRP-(1-36)NH2 (125I-[Tyr36]hPTHRP-(1-36)NH2) was identified in 75% of unselected SqCC lines. In contrast, no binding was detected on the mouse keratinocyte line BALB-MK or on five different HK lines. Although each SqCC and keratinocyte line secreted immunoreactive PTHRP into its medium, there was no correlation between PTHRP concentration and number of binding sites. Inhibition of binding by [Tyr36]hPTHRP-(1-36)NH2 yielded half-maximal inhibitory concentration values of approximately 100 nM in all SqCC lines. Affinity cross linking of SqCC cells revealed 98- and 70-kDa binding proteins with similar affinity (approximately 100 nM). Exposure of fura-2-loaded SqCC cells to PTHRP and PTH resulted in equivalent, dose-dependent transient increases in intracellular calcium [half-maximal effective concentration (EC50) = 0.08 nM]. PTHRP also increased intracellular calcium in HK (EC50 = 0.05 nM). No adenosine 3',5'-cyclic monophosphate (cAMP) response to PTHRP or PTH was elicited in either SqCC or HK, despite brisk isoproterenol responses in both. We conclude that high capacity low-affinity binding sites for PTHRP are detectable in the majority of SqCC lines but not in HK. These low-affinity binding sites are unlikely to represent receptors. The sensitive intracellular calcium response suggests the additional presence of high-affinity receptors on SqCC as well as on HK. However, the failure of PTHRP or PTH to stimulate cAMP production in otherwise cyclase competent cells suggests that these are not classical PTH receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590372 TI - Effects of maturation and aging on the skeletal muscle glucose transport system. AB - Insulin resistance in old, compared with young, humans and animals has been well documented. The resistance is due primarily to defects in skeletal muscle. In the present study, skeletal muscle sarcolemmal membranes were purified from five age groups of female Fischer rats ranging from 2 to 24 mo. Basal specific D-glucose transport was not significantly different among any of the groups. Maximum insulin-stimulated transport was progressively decreased from 96.4 +/- 5.0 pmol.mg-1.15 s-1 in the 2-mo-old animals to 70.8 +/- 8.9 pmol.mg-1.15 s-1 in the 24-mo-old animals. Most of the decrease occurred during maturation, and in fact there was no significant difference in maximum transport among the 8-, 16-, and 24-mo-old rats. The decrease in insulin-stimulated transport in the 24-mo-old animals was due to a reduction in the number of glucose transporters translocated into the sarcolemma membrane (9.8 +/- 0.6 vs. 7.8 +/- 0.6 pmol/mg protein). The intracellular or microsomal pool of glucose transporters was not significantly different between the 2- and 24-mo-old animals (8.8 +/- 0.6 vs. 8.5 +/- 0.9/mg protein). Western blotting revealed no differences in the cellular GLUT-4 contents between the 2- and 24-mo-old rats. The number of insulin receptors (2.3 +/- 0.4 vs. 2.1 +/- 0.5 pmol/mg protein) was not significantly different. Tyrosine kinase activity of the insulin receptor was, however, significantly reduced in the 24-mo-old compared with the 2-mo-old animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590373 TI - Carbohydrate restriction regulates the adaptive response to fasting. AB - The importance of either carbohydrate or energy restriction in initiating the metabolic response to fasting was studied in five normal volunteers. The subjects participated in two study protocols in a randomized crossover fashion. In one study the subjects fasted for 84 h (control study), and in the other a lipid emulsion was infused daily to meet resting energy requirements during the 84-h oral fast (lipid study). Glycerol and palmitic acid rates of appearance in plasma were determined by infusing [2H5]glycerol and [1-13C]palmitic acid, respectively, after 12 and 84 h of oral fasting. Changes in plasma glucose, free fatty acids, ketone bodies, insulin, and epinephrine concentrations during fasting were the same in both the control and lipid studies. Glycerol and palmitic acid rates of appearance increased by 1.63 +/- 0.42 and 1.41 +/- 0.46 mumol.kg-1.min-1, respectively, during fasting in the control study and by 1.35 +/- 0.41 and 1.43 +/- 0.44 mumol.kg-1.min-1, respectively, in the lipid study. These results demonstrate that restriction of dietary carbohydrate, not the general absence of energy intake itself, is responsible for initiating the metabolic response to short-term fasting. PMID- 1590374 TI - ATP depletion stimulates calcium-dependent protein breakdown in chick skeletal muscle. AB - The contribution of metabolic energy to the degradation of intracellular proteins in skeletal muscle was investigated. Isolated chick skeletal muscles deprived of oxygen and muscles incubated in buffer under nonphysiological conditions containing inhibitors of glycolysis and mitochondrial respiration had lower concentrations or undetectable levels of ATP and faster rates of proteolysis. Both total protein breakdown and the breakdown of myofibrillar proteins were stimulated 35-124% in ATP-depleted tissues. However, ATP-depleted muscles incubated in buffer to which no Ca2+ was added showed slower rates of total protein breakdown and no significant change in myofibrillar proteolysis compared with control muscles. Trans-epoxysuccinyl-L-leucylamido(4-guanidino)butane (E 64), a compound that inhibits the calpains and the lysosomal cysteine proteases, completely blocked the Ca(2+)-stimulated breakdown of nonmyofibrillar and myofibrillar proteins in ATP-depleted muscles. However, Ca(2+)-stimulated proteolysis was not inhibited in ATP-depleted muscles incubated with weak bases to prevent lysosome function. These data suggest that intracellular proteins can be degraded in skeletal muscle in the absence of metabolic energy and that the calpains play a major role in the enhanced proteolysis in skeletal muscles depleted of ATP. PMID- 1590375 TI - Monitoring thromboxane in body fluids: a specific ELISA for 11-dehydrothromboxane B2 using a monoclonal antibody. AB - 11-Dehydrothromboxane B2 (11-DHTxB2) concentrations are believed to reflect levels of the in vivo synthesis and release of thromboxane A2. In a specific enzyme-linked immunosorbent assay (ELISA) a monoclonal antibody (MAB) against 11 DHTxB2 (MAB-1E-DHTBR1) recognizes the acyclic form of 11-DHTxB2, as found in the basic range of pH, with a detection limit of 4.6 pg/sample and a binding affinity of 6.1 x 10(9) l/mol. Negligible cross-reactivity was found for thromboxane B2 (0.05%), 2,3-dinor-thromboxane B2 (0.06%), and prostaglandin D2 (0.08%). Validity of the assay was confirmed by a good correlation between radioimmunoassay and ELISA (r = 0.972). Recovery experiments showed an accuracy of r = 0.982. Measurements of 11-DHTxB2 in human serum and urine samples demonstrated the practical applicability of the MAB in ELISA. With the use of different clotting times, the serum level of 11-DHTxB2 ranged from 0.8-1.3 ng/ml (30 min) to 24.1 47.9 ng/ml (4 h). After administration of aspirin the 11-DHTxB2 level of human urine declined from 3.9-5.4 ng/ml to 0.4-1.6 ng/ml after 6 h. PMID- 1590376 TI - Lipoprotein lipase release from cardiac myocytes is increased by decavanadate but not insulin. AB - Streptozotocin-induced diabetes reduced cellular lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts and decreased the heparin-induced release of LPL into the medium. This effect of diabetes was rapidly reversed by in vivo treatment with insulin (5 U iv for 1 h); administration of insulin in vivo to control rats also increased heparin-releasable LPL activity. In contrast, in vitro addition of insulin to control and diabetic myocytes did not alter either cellular or heparin-releasable LPL activities. Insulin stimulated glucose oxidation and protein synthesis in control and diabetic myocytes. Decavanadate (0.05-1 mM) or vanadyl ion (0.5 mM) enhanced the release of LPL into the medium. Heparin- and decavanadate-induced release of LPL was not additive, and heparin pretreatment reduced the subsequent release of LPL by decavanadate. Decavanadate displaced LPL bound to heparin-Sepharose and increased LPL release into the perfusate of hearts. Therefore, decavanadate can mimic heparin in its effect on LPL. The absence of a direct in vitro effect of insulin on LPL in cardiac myocytes suggests that insulin may require some other in vivo factor or that diabetes-induced changes in LPL activity are secondary to some other metabolic factor. PMID- 1590377 TI - Role of hepatic nerves in response of liver to intraportal glucose delivery in dogs. AB - Net hepatic glucose uptake (NHGU) is much greater during oral or intraportal glucose loading than during peripheral intravenous glucose delivery even when similar glucose loads and hormone levels reaching the liver are maintained. To determine whether this difference is influenced by the hepatic nerves, nine conscious 42-h-fasted dogs in which a surgical denervation of the liver (liver norepinephrine levels postdenervation averaged 2.4% of normal) had been performed were subjected to a 40-min control period and two randomized 90-min test periods during which somatostatin (0.8 microgram.kg-1.min-1), intraportal insulin (1.2 mU.kg-1.min-1), and intraportal glucagon (0.5 ng.kg-1.min-1) were infused. The glucose load to the liver was increased twofold by infusing glucose into a peripheral vein (Pe) or the portal vein (Po). Arterial insulin and glucagon concentrations were 39 +/- 2 and 39 +/- 3 microU/ml and 55 +/- 5 and 54 +/- 7 pg/ml during Pe and Po, respectively. The hepatic glucose loads were 50.3 +/- 4.4 and 51.4 +/- 5.8 mg.kg-1.min-1 while NHGU was 2.1 +/- 0.5 and 2.2 +/- 0.7 mg.kg 1.min-1 during Pe and Po, respectively. Similar hormone levels and glucose loads reaching the liver in dogs with intact hepatic nerve supplies were previously shown to be associated with NHGU of 1.4 +/- 0.7 and 3.5 +/- 0.8 mg.kg-1.min-1 in the presence of peripheral and portal glucose delivery, respectively. In conclusion, an intact nerve supply to the liver appears to be vital for the normal response of the liver to intraportal glucose delivery. PMID- 1590378 TI - Splanchnic and whole body L-[1-13C,15N]leucine kinetics in relation to enteral and parenteral amino acid supply. AB - The effect of the route of administration of a complete amino acid solution (0.24 g.kg-1.h-1) on leucine (Leu) and alpha-ketoisocaproate (KIC) metabolism in the splanchnic region (Sp) was assessed in nine chronically catherized mongrel dogs receiving, for 6 h, amino acids by jugular vein (PN feeding). Results were compared with those obtained previously [Y. M. Yu, D. A. Wagner, E. E. Tredget, J.A. Waleszewski, J. F. Burke, and V. R. Young. Am. J. Physiol. 259 (Endocrinol. Metab. 22): E36-E51, 1990] in eight dogs similarly studied but given amino acids by constant enteral feeding (EN). We used primed continuous intravenous infusions of L-[1-13C,15N]Leu and measurements of arteriovenous isotope and Leu balance across the gut, liver, and Sp to estimate parameters of whole body and organ Leu metabolism [Leu-N and Leu-C flux, Leu----KIC; KIC----Leu, Leu oxidation and rates of Leu appearance (B) from and disappearance (S) into proteins]. Whole body Leu kinetics were the same for both routes of amino acid administration. With PN, KIC ---Leu, Leu----KIC, and total metabolic processing were lower than for EN in Sp, and overall Leu balance (S - B) was higher in Sp for EN. Leu appearance from protein breakdown in gut was higher with PN. The rate of KIC----Leu was higher in liver for EN. These findings reveal that route of amino acid (Leu) administration, under these acute feeding conditions, alters the processing and metabolic fate of Leu in Sp but that whole body parameters of Leu metabolism are stable. The implications of these metabolic findings in relation to the maintenance of intestinal function and integrity are discussed. PMID- 1590379 TI - Effects of insulin and dexamethasone on lipoprotein lipase in human adipose tissue. AB - The mechanisms by which insulin and glucocorticoids modulate lipoprotein lipase (LPL) synthesis and degradation were examined in human adipose tissue fragments maintained in organ culture. Tissue fragments were cultured for 7 days in serum free medium supplemented with or without insulin (7 nM) and with or without dexamethasone (30 nM), a synthetic glucocorticoid. Responses of LPL activity to both insulin and dexamethasone were obtained at doses within the physiological range. At a maximal dose, insulin increased heparin-releasable and total LPL activity (approximately 7-fold) by specifically increasing the rate of LPL synthesis (approximately 5-fold) determined by pulse labeling with [35S]methionine and [35S]cysteine and immunoprecipitation. Dexamethasone added in the presence of insulin increased heparin-releasable and total LPL activity approximately 8-fold but did not alter rates of LPL synthesis compared with insulin alone. Pulse-chase studies showed that the rate of LPL degradation was markedly slowed in the presence of dexamethasone plus insulin compared with insulin alone. These data suggest that, in human adipose tissue, insulin is essential for maintaining rates of LPL synthesis and that cortisol may play a key role in regulating human adipose tissue LPL at the posttranslational level by inhibiting the degradation of newly synthesized LPL. PMID- 1590380 TI - Kinetics of glucose transport in rat skeletal muscle membrane vesicles: effects of insulin and contractions. AB - To study the mechanism of acceleration of glucose transport in skeletal muscle after stimulation with insulin and contractions, we isolated a subcellular vesicular membrane fraction, highly enriched in the plasma membrane enzyme K(+) stimulated p-nitrophenylphosphatase and also enriched in some intracellular membranes. Protein recovery, morphology, lipid content, marker enzyme activities, total intravesicular volume, Western blot quantitation of GLUT-1, and glucose inhibitable cytochalasin B binding were identical in membrane fractions from control, insulin-stimulated, contraction-stimulated, and insulin- and contraction stimulated muscle. Time course of D-[3H]glucose entry in membrane vesicles at equilibrium exchange conditions showed that initial rate of transport at 30 mM of glucose was increased 19-fold and that equilibrium distribution space was increased 4-fold in vesicles from maximum stimulated muscle. The effects of insulin and contractions on initial rate of transport as well as on equilibrium distribution space were additive, and stimulation increased the substrate saturability of glucose transport. Furthermore, cytochalasin B binding to membranes prepared by using less centrifugation time than usual showed that, after stimulation with insulin and contractions, at least 35% of the total number of glucose transporters were redistributed from one kind of vesicles to a more slowly sedimenting kind of vesicles, probably reflecting translocation within the membrane preparation from intracellular vesicles to the plasma membrane upon stimulation. In the present membrane preparation the effects of insulin and/or contractions on glucose transport resemble those seen in intact muscle, and the effects are thus not dependent on cellular integrity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590381 TI - Binding of thyroxine and 3,5,3'-triiodothyronine to trout plasma lipoproteins. AB - The plasma vectors of thyroid hormones (TH) in trout have been characterized. Plasma components were separated by density gradient ultracentrifugation after first labeling binding sites with trace levels of radioactive hormones, both in vivo and in vitro. Lipoproteins play only a minor role in humans but are major carriers of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in trout plasma. More than 67% of T4 and 89% of T3 were bound to lipoproteins (density less than 1.210 g/ml), predominantly to high-density lipoproteins (HDL), regardless of the nutritional status of the animals. The percentage of hormone bound to very-low density lipoproteins, on the other hand, was proportional to their concentration and thus to nutritional status. T3 and T4 could also bind to vitellogenin, a very high-density lipoprotein, which could transfer TH to the yolk of oocytes. Homologous ligand displacement indicated that T3 could bind to at least two classes of saturable sites in the plasma. In addition, plasma HDL were the major binding sites with low affinity (1.7 +/- 0.4 x 10(5) M-1) but with high capacity (3.1 +/- 0.3 x 10(-5) M). In conclusion, these results show that lipoproteins are the principal binding sites of TH in trout plasma. PMID- 1590382 TI - A substantial part of GLUT-1 in crude membranes from muscle originates from perineurial sheaths. AB - The distribution of GLUT-1 and GLUT-4 in cryosections of rat skeletal muscles was investigated immunocytochemically. Intense labeling of GLUT-1 was found in the perineurial sheaths of intramuscular nerves, whereas only a very faint signal was associated with the sarcolemma, and labeling of extraneural vessels was not detectable. The majority of the GLUT-4 reactivity was located at the periphery of muscle cells in nonuniform patches, and GLUT-4 was absent in vessels and nerves. In sections of femoral nerve GLUT-1 was confined to the perineurial sheath and endoneurial vessels. The contribution of GLUT-1 from intramuscular perineurial sheaths to total GLUT-1 in a muscle was determined from immunoblots of crude membranes isolated from mixtures of homogenates of excised nerves and muscles. The recovery of GLUT-1 increased linearly with the amount of nerve added, and it was calculated that GLUT-1 from intramuscular perineurial sheaths accounted for approximately 60% of the GLUT-1 content in a membrane fraction from soleus muscle or red gastrocnemius. The remaining 40% of GLUT-1 is likely to originate from the sarcolemma. PMID- 1590383 TI - Sepsis-induced cascade of cytokine mRNA expression: correlation with metabolic changes. AB - The relationships between metabolic alterations and tissue-specific gene expression of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), gamma-interferon (gamma-IFN), and interleukin 1 and serum levels of TNF-alpha and IL-6 before and after a live Escherichia coli septic challenge to rats were examined. From 0 to 2 h, serum glucose significantly decreased while plasma glucagon increased. By 8 h, plasma glucagon, serum insulin, and glucose appearance were significantly elevated. Gene expression of phosphoenolpyruvate carboxykinase increased 1 h after E. coli but by 4 h was significantly decreased. TNF-alpha mRNA (liver and spleen) and serum peptide levels peaked 1-2 h after the septic challenge and then decreased substantially by 6-8 h. Spleen IL-6 and gamma IFN mRNA expression reached a maximum 4 h after E. coli challenge, whereas serum IL-6 levels were elevated by 2 h after injection of the bacteria. The increase in TNF-alpha mRNA and serum peptide levels correlated with the early fall in serum glucose and rise in plasma glucagon. Alterations in the rate of glucose appearance and plasma glucagon were observed later and coincided with the increased mRNA expression of IL-6 and gamma-IFN. Thus the metabolic alterations observed in the septic rat are associated with a complex cascade of several cytokines. PMID- 1590384 TI - Increased islet blood flow in obese rats: role of the autonomic nervous system. AB - Hyperinsulinemia, a main feature of both human and animal obesity, has been demonstrated to be due to both an increased sensitivity to nutrient secretagogues and an impairment of the nervous regulation of insulin secretion. Recent studies have shown that pancreatic islet blood flow increases under conditions associated with an enhanced insulin secretion. The aim of this study was to determine whether or not changes in islet blood flow are present in hyperinsulinemic obese rats. Using the nonradioactive microsphere technique, we were able to show a significantly higher islet blood flow in obese rats either of the Zucker strain or Wistar rats after lesion of the ventromedial hypothalamus than in their respective lean controls. Subdiaphragmatic vagotomy had no significant effect on basal islet blood flow of lean rats, whereas it decreased significantly that of obese Zucker rats. Conversely, clonidine, an alpha 2-adrenergic agonist, induced a higher decrease of islet blood flow in obese than in lean Zucker rats. The injection of an intravenous bolus of glucose (375 mg/kg iv) increased significantly more islet blood flow in obese than in lean Zucker rats. It is concluded that obese rats present an increased pancreatic islet blood flow, which may result, at least in part, from exaggerated parasympathetic activity and lower than normal sympathetic activity. This could participate in the hyperinsulinemia observed in these rats. PMID- 1590385 TI - Quantification of hormone pulsatility via an approximate entropy algorithm. AB - Approximate entropy (ApEn) is a recently developed formula to quantify the amount of regularity in data. We examine the potential applicability of ApEn to clinical endocrinology to quantify pulsatility in hormone secretion data. We evaluate the role of ApEn as a complementary statistic to widely employed pulse-detection algorithms, represented herein by ULTRA, via the analysis of two different classes of models that generate episodic data. We conclude that ApEn is able to discern subtle system changes and to provide insights separate from those given by ULTRA. ApEn evaluates subordinate as well as peak behavior and often provides a direct measure of feedback between subsystems. ApEn generally can distinguish systems given 180 data points and an intra-assay coefficient of variation of 8%. This suggests ApEn as applicable to clinical hormone secretion data within the foreseeable future. Additionally, the models analyzed and extant clinical data are both consistent with episodic, not periodic, normative physiology. PMID- 1590386 TI - Evaluation of four mathematical models of glucose and insulin dynamics with analysis of effects of age and obesity. AB - Despite there being a number of mathematical models of glucose and insulin dynamics, there have been no evaluations of their operation in large groups of subjects. We have carried out intravenous glucose tolerance tests on a group of 182 healthy males, with determination of plasma glucose, insulin, and C-peptide concentrations. Parameters of glucose and insulin dynamics were determined using the minimal model of glucose disappearance, a minimal model of peripheral insulin delivery, and two different models of pancreatic insulin secretion (models I and II). Successful identifications were obtained in 96, 95, 76, and 100% of cases, respectively. The models were evaluated in terms of their ability to recover effects of obesity and aging on carbohydrate metabolism. The glucose disappearance model successfully detected the insulin resistance of both obesity and aging, whereas the peripheral insulin delivery model indicated an increased responsiveness of insulin delivery to glucose in obesity but detected no significant change associated with age. No parameter of pancreatic secretion model I exhibited a significant association with either age or obesity. Insulin secretion model II indicated that the hyperinsulinemia accompanying obesity resulted from both increased pancreatic secretion and decreased hepatic insulin uptake. PMID- 1590387 TI - Gastric inhibitory polypeptide stimulates pancreatic lipase and colipase synthesis in rats. AB - Effects of short-term infusion and long-term injection of gastric inhibitory polypeptide (GIP) on changes in pancreatic lipase and colipase contents in rats were studied, and mRNAs encoding for lipase and colipase were determined by Northern blot hybridization with specific cDNA probes. GIP infused at a dose of 3 micrograms/h for 24 h significantly increased the pancreatic lipase content by 34% (P less than 0.05) but had no significant effect on colipase and amylase contents. No change in mRNAs encoding for these proteins was found after infusion of GIP for 24 h. Injection of GIP (5-60 micrograms/kg) three times a day for 5 days dose dependently increased the contents of lipase and colipase, with the increase in colipase being more prominent. Injection of GIP for 5 days at a dose of 30 micrograms.kg-1.day-1 increased colipase and lipase contents by 52 and 25%, and their corresponding mRNAs by 60 and 160%, respectively. The amylase mRNA was not changed by injection of GIP. It is concluded that GIP has a specific stimulatory effect on the synthesis of pancreatic lipase and colipase at both pretranslational and translational levels. PMID- 1590388 TI - Effect of intravascular ethanol on modulation of gastric mucosal integrity: possible role of endothelin-1. AB - The influences of intravascular ethanol on gastric mucosal integrity and its relation to gastric circulation were investigated in rats. Ulcer formation of the gastric mucosa correlated with the blood ethanol concentration in the presence of 150 mM HCl in the rat stomach. Furthermore, the gastric mucosal hemoglobin concentration (IHb) and hemoglobin oxygen saturation (ISO2), estimated using organ reflectance spectrophotometry, decreased in a concentration-dependent manner with blood ethanol. In isolated, vascularly perfused rabbit stomach, various concentrations (10-400 mM) of ethanol infused into the celiac artery increased the perfusion pressure and released endothelin-1 (ET-1) from the gastric vasculature in a concentration-dependent manner. Moreover, a significant correlation existed between changes in the perfusion pressure and ET-1 concentration in effluents from the gastric vasculature. Furthermore, anti-ET-1 antibody reduced 100 mM ethanol-induced vasoconstriction in a concentration dependent manner. The results indicate that intravascular ethanol increases the susceptibility of gastric mucosa to injury induced by intraluminal HCl by causing gastric vasoconstriction mediated by ET-1. Thus intravascular ethanol may play an important role in the mechanism of ethanol-induced gastric mucosal injury. PMID- 1590389 TI - Role of calcium in monitor peptide-stimulated cholecystokinin release from perifused intestinal cells. AB - Monitor peptide stimulates cholecystokinin (CCK) release from the intestine, but the cellular mechanisms responsible for this effect are uncertain. In the present study, the roles of membrane potential difference and calcium influx in monitor peptide-mediated CCK release were examined in a perifusion system containing isolated mucosal cells from the rat duodenum. This method represents an in vitro system in which CCK-releasing cells can be challenged with secretagogues or other maneuvers to study the dynamics of hormone secretion. High concentrations of KCl (50 mM), which reduce electrical potential difference across the cell membrane, caused the release of CCK. This effect was inhibited by the calcium channel blocker MnCl2. Monitor peptide stimulated CCK release in a dose-dependent manner at concentrations from 3 x 10(-12) to 3 x 10(-8) M. The requirement for extracellular calcium in secretagogue-stimulated release of CCK was investigated using ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA), a calcium chelator, and MnCl2. A calcium-free environment supplemented with 2 mM EGTA completely inhibited CCK secretion in response to stimulatory doses of monitor peptide. CCK secretion was restored when calcium was reintroduced into the system. Similarly, MnCl2 completely blocked monitor peptide stimulated CCK release. These data indicate that membrane depolarization and monitor peptide stimulate the release of CCK through calcium-dependent mechanisms, suggesting that increases in intracellular calcium within CCK cells are likely to be important in CCK release. PMID- 1590390 TI - Regulatory volume decrease stimulates bile flow, bile acid excretion, and exocytosis in isolated perfused rat liver. AB - To study the effect of volume regulation on bile secretory function, isolated perfused rat livers (IPRL) were exposed to hypotonic stress (45 mM NaCl) while bile flow and the biliary excretion of bile acids and horseradish peroxidase (HRP) were assessed. Hypotonic stress induced a biphasic increase in bile flow, which rose in the first minute from 1.1 +/- 0.2 to 1.7 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01), an effect attributed to rapid osmotic equilibration of water, then increased further between 3 and 5 min to 1.6 +/- 0.1 microliter.min-1.g liver-1 (P less than 0.01, followed by a subsequent return to baseline. HRP excretion in bile increased during the second peak of bile flow from 0.9 +/- 0.2 to 1.1 +/- 0.2 ng.min-1.g liver-1, P less than 0.01. Pretreatment with colchicine but not lumicolchicine completely abolished the latter increase in bile flow and HRP excretion as did BaCl2 (1 mM), an inhibitor of both K+ channels and regulatory volume decrease (RVD) in hepatocytes. When sodium taurocholate was infused (1 mumol/min), hypotonic stress induced an even larger increase in the second peak of bile flow (5.1 +/- 0.7 microliters/g liver, P less than 0.01) and higher rates of bile acid excretion than in control perfusions with bile acid (126.2 +/- 21.0 vs. 99.0 +/- 17.1 nmol.min-1.g liver-1, P less than 0.05). These data suggest that both bile flow and bile acid excretion are stimulated during RVD by mechanisms that involve both K+ channels and microtubule-dependent exocytosis at the canalicular (apical) membrane domain. PMID- 1590391 TI - Effect of short-chain fatty acids on contractile activity and fluid flow in rat colon in vitro. AB - The effect of short-chain fatty acids (SCFAs) on the contractile activity and fluid output of the large bowel of the rat was studied using an isolated segment of cecum and colon, mounted in vitro. The rate of contractile activity per minute in the proximal, mid, and distal regions of the colon was depressed by luminal infusion of associated SCFAs either as a mixture (acetic, propionic, and butyric) or individually (100 mM/pH = 4.1, in each case). Dose responses were observed for the individual fatty acids, with the 100 mM solutions eliciting a more prominent reduction in colonic motor activity than that induced by 10 mM. Neither the Na salt of the fatty acids nor an acidified Krebs solution (pH = 4.1) inhibited contractile activity or fluid output. No reduction in the rate of contractile activity was observed in the cecum with any test solutions, except 100 mM butyric acid. The data suggest that SCFAs inhibit smooth muscle contractility and resultant fluid transit. PMID- 1590392 TI - Acceleration of gastric emptying with electrical stimulation in a canine model of gastroparesis. AB - We investigated the effects of electrical stimulation of the stomach on gastric emptying and the electrical activity of the stomach in 10 dogs. A model of gastroparesis was developed in five dogs using truncal vagotomy combined with injections of glucagon. Glucagon also induced electrical dysrhythmias. Bipolar electrodes were implanted in the stomach and the duodenum for electrical stimulation and for recording electrogastrograms. Gastric emptying of an isotope labeled solid meal was assessed for 2 h. External electrical stimulation was delivered to the corpus of the stomach at its own physiological frequency to investigate whether it could restore normal gastric emptying. Such stimulation had no significant effect on gastric emptying in intact animals (45 vs. 43%: retention of isotope after 2 h) or when only vagotomy was performed (78 vs. 66%), but it significantly accelerated gastric emptying in animals with vagotomy and glucagon (from 86 to 68%). From this model of delayed gastric emptying, we suggest that electrical stimulation of the stomach at its own intrinsic frequency may recoordinate uncoupled slow wave activity induced by glucagon after vagotomy thus improving the rate of gastric emptying. PMID- 1590393 TI - Gastric acid secretory responses induced by peptone are mediated by capsaicin sensitive sensory afferent neurons. AB - The involvement of capsaicin-sensitive afferent neurons in modulating acid secretory responses to peptone, a product of protein digestion, has been investigated in the continuously perfused stomach of the urethan-anesthetized rat. Systemic neonatal pretreatment with capsaicin, which destroys primary afferent neurons, does not modify basal levels of acid secretion. Acid responses to intragastric perfusion with isotonic (0.5, 1, and 2.4%) or hypertonic (10 and 20%) solutions of peptone were reduced in capsaicin-treated rats. Intragastric perfusion with hypertonic mannitol (18%) did not stimulate secretion of acid. Systemic capsaicin pretreatment did not modify acid responses to intraperitoneal histamine (5 mg/kg) or pentagastrin (100 micrograms/kg). Acute intragastric perfusion (10 min) with capsaicin (0.3 mg/ml), tetrodotoxin (150 ng/ml), or the combination of both neurotoxins reduced the acid responses to 1% peptone to levels not different from those of animals treated systemically with capsaicin. Bilateral vagotomy or acute celiac ganglionectomy also decreased acid responses to 1% peptone in control animals, without modifying the diminished responses to peptone in rats treated systemically with capsaicin. Gastric acid secretory responses in rats undergoing both vagotomy and celiac ganglionectomy were not lower than those obtained after each surgical procedure alone. These findings suggest that peptone stimulates acid secretion in the rat partially by activating a nervous reflex mediated by capsaicin-sensitive sensory afferent fibers. The reflex arc involves fibers that would terminate in the gastric mucosa and project to, or from, the central nervous system through the vagus and the celiac ganglion. PMID- 1590394 TI - Action profiles of nitric oxide, S-nitroso-L-cysteine, SNP, and NANC responses in opossum lower esophageal sphincter. AB - Circular muscle strips from opossum lower esophageal sphincter were suspended in organ baths for measurement of isometric tension. Nonadrenergic noncholinergic (NANC) inhibitory nerves were stimulated by means of transmural field stimulation. This induced frequency-dependent relaxations of the muscle strips. Methylene blue (3 x 10(-6) M; inhibits guanylate cyclase) and pyrogallol (10(-4) M; generates superoxide anions) had no influence on relaxations, whereas oxyhemoglobin [10(-5) M; binds nitric oxide (NO) and other nitroso compounds extracellularly] inhibited relaxations at all frequencies. NO concentration dependently relaxed the muscle strips. Pyrogallol (10(-4) M) and methylene blue (3 x 10(-6) M) inhibited and oxyhemoglobin (10(-5) M) nearly abolished relaxation induced by NO. S-nitroso-L-cysteine caused concentration-dependent relaxations of the muscle strips, which were inhibited by pyrogallol (10(-4) M), whereas methylene blue (3 x 10(-6) M) augmented the action of S-nitroso-L-cysteine. Methylene blue (3 x 10(-6) M) had no influence on the concentration-dependent relaxations caused by sodium nitroprusside (SNP). Oxyhemoglobin (10(-5) M), and to a lesser extent pyrogallol (10(-4) M), both inhibited the effects of SNP. The action profiles for S-nitroso-L-cysteine, NO, and SNP differed from the action profile for NANC nerve-mediated response. Although pyrogallol inhibited the effects of SNP, the action profile generally resembled the action profile for NANC responses more closely than did the profiles for S-nitroso-L-cysteine or NO. In conclusion, of the nitroso compounds studied, SNP most closely resembled the response to NANC nerve stimulation. Neither NO nor S-nitroso-L-cysteine individually mimicked the NANC response. PMID- 1590395 TI - Ontogeny of intestinal phosphate absorption in rabbits. AB - The ontogeny of intestinal phosphate transport was examined in brush-border membrane vesicles prepared from 2-wk, 4-wk, 6-wk, and 3-mo-old rabbits. At all four ages, vesicles prepared from the duodenum demonstrated sodium-phosphate cotransport in that uptake in the presence of a sodium gradient was significantly greater than uptake in the presence of a potassium gradient. While sodium independent phosphate uptake was comparable at all ages, sodium-phosphate cotransport was greatest in the youngest animals and declined with increasing age. Peak phosphate uptake was 10-fold the equilibrium value at 2 wk and declined to 3-fold in adults. Maximal transport capacity of sodium-phosphate cotransport fell from 2,292 +/- 161 at 2 wk to 286 +/- 12 pmol.mg-1.10 s-1 at 3 mo, whereas the Michaelis constant did not change with age, varying between 0.032 and 0.054 mM. At all ages, uptake was half-maximally stimulated between 30 and 50 mM sodium, and Hill coefficients were between 1.5 and 2. Generation of inside negative diffusion potentials did not significantly enhance phosphate uptake at any age. These data suggest that throughout development, the transport of each phosphate molecule across the rabbit duodenal brush-border membrane is coupled to the transport of two sodium molecules. There were distinct developmental changes in the distribution of the sodium-phosphate cotransport along the length of intestine. In 2-wk old animals, sodium-phosphate cotransport was present in the duodenum, proximal and distal jejunum, and proximal ileum. In 4-wk-old animals, sodium-phosphate cotransport was present throughout the duodenum and proximal and distal jejunum, and in 6-wk and 12-wk-old animals, sodium-phosphate cotransport was observed only in the duodenum and proximal jejunum. PMID- 1590396 TI - Evidence for intestinal release of absorbed selenium in a form with high hepatic extraction. AB - Selenium is readily absorbed from the gastrointestinal tract and utilized for synthesis of selenoproteins. Roles of intestine, liver, and selenoprotein P in this process were evaluated. Rats were given 75Se-selenite by stomach tube, and distribution of 75Se was followed for 3 h. A high portal vein plasma-to-hepatic vein plasma ratio of 75Se 15 min after 75Se administration and earlier uptake by liver than by other tissues indicated avid hepatic extraction of absorbed selenium from portal vein blood. The results of gel filtration of plasma taken 15 min after 75Se administration suggested that the 75Se was in the form of small molecules with some affinity for protein. Immunoprecipitation studies using plasma indicated that 75Se began to appear in selenoprotein P between 15 and 30 min after intragastric administration. To evaluate the role of the liver in the fate of absorbed selenium, rats with portacaval shunts, in which absorbed selenium bypasses the liver, were compared with sham-operated rats. After intragastric administration of selenium, uptake by the liver and incorporation into selenoprotein P were diminished in rats with portacaval shunts but kidney uptake and urinary excretion were increased. This suggests that hepatic extraction of absorbed selenium from portal vein blood decreases its entrance into the systemic circulation. The results of this study indicate that intestine releases absorbed selenium into portal blood in a small-molecule form, designated A-Se, which is highly extracted by the liver. The liver takes up A-Se better than other tissues because of a high extraction capacity and the fact that it is the first organ through which the blood from the intestine passes. PMID- 1590398 TI - Postnatal development of monosaccharide transport in pig intestine. AB - In vitro brush-border transport of three monosaccharides by pig intestine was studied as a function of postnatal age from immediately after birth before suckling to after weaning. Rates of transport normalized to tissue weight or surface area for glucose (Glc), galactose (Gal), and fructose (Fru) were highest at birth, with a steep decline after the onset of suckling, probably caused by any combination of three or more factors: reduced transporter site density, shifts in relative abundances of different monosaccharide transporters, and/or changes in activities of individual transporters. Whereas highest rates of Glc and Fru transport shifted from proximal to midintestine after weaning, Gal transport remained highest in proximal intestine. Postnatal increases in Km values for Gal, but not Glc, indicate there are multiple aldohexose transporters that undergo separate developmental trajectories. The presence of Fru transport in neonatal pigs may reflect a more advanced state of development than neonatal rats and rabbits, or may be an adaptation for early weaning. Changes in Fru-to Glc and Gal-to-Glc transport ratios before weaning suggest transporter development is partly genetically hard-wired, apparently to prepare pigs for weaning. Curiously, Fru-to-Glc transport ratios were lower than those of rat and rabbit, but closely paralleled those of the carnivorous cat. PMID- 1590397 TI - Uptake of palmitate by hepatocyte suspensions: facilitation by albumin? AB - Albumin-dependent uptake of unbound [3H]palmitic acid by hepatocytes isolated from female rat livers was studied and the experimental results compared with the predictions of a noncompartmental diffusion-reaction theory for the cellular uptake of protein-bound ligands. The outright theoretical predictions involve values for the parameters of the system, some newly measured (hepatocyte radii and the rate constant for the dissociation of palmitate-albumin complex) and some taken from the literature (diffusion coefficients and the equilibrium association constant for the palmitate-albumin complex). The measured unbound clearance of [3H]palmitic acid, defined as the initial uptake velocity divided by the unbound [3H]palmitic acid concentration in the medium, was enhanced 6.6-fold as the concentration of human serum albumin was increased from approximately 5 to 480 microM. This enhancement factor was predicted by the theory, according to which the enhancement reflects codiffusion of bound ligand across the unstirred layer adjacent to the cell membrane and, therefore, an increased delivery of unbound ligand to the cell surface. In contrast, the absolute magnitude of the unbound clearance was consistent with the theory only for the lowest published value for the equilibrium association constant, 15 microM-1. For higher published values (62 and 94 microM-1), the magnitude of the unbound clearance observed experimentally was severalfold higher than that predicted by the theory. If in fact the association constant exceeds 30 microM-1, the data would imply that an albumin-dependent facilitation mechanism exists which enhances the availability of palmitate to the cell over and above the enhancement predicted by the diffusion-reaction theory. PMID- 1590399 TI - Effect of octreotide on sphincter of Oddi and gallbladder motility in prairie dogs. AB - Somatostatin and its synthetic analogue, octreotide, inhibit gallbladder emptying and cause gallstones. Whether octreotide-induced alterations in sphincter of Oddi motility contribute to this process is unknown. We, therefore, examined the effect of octreotide on fasting and protein-stimulated sphincter of Oddi motility. In 25 anesthetized prairie dogs, sphincter of Oddi motility and gallbladder pressure were monitored during the intravenous administration of octreotide, cholecystokinin (CCK) octapeptide, atropine, the intraduodenal administration of casein, and combinations of these agents. Intravenous octreotide decreased fasting sphincter of Oddi motility index both with (59 +/- 19 vs. 84 +/- 28, P less than 0.05) and without (137 +/- 31 vs. 227 +/- 42, P less than 0.05) prior cholinergic blockade with atropine. Octreotide also prevented the increases in sphincter of Oddi motility and gallbladder pressure seen with intraduodenal casein. Exogenous CCK increased sphincter of Oddi motility index and gallbladder pressure despite the simultaneous administration of octreotide alone (357 +/- 109 vs. 137 +/- 31, P less than 0.07, and 11.2 +/- 1.0 mmHg vs. 9.6 +/- 0.6 mmHg, P less than 0.05) or the combination of octreotide and atropine (317 +/- 69 vs. 59 +/- 19, P less than 0.05, and 10.1 +/- 1.6 mmHg vs. 8.5 +/- 1.4 mmHg, P less than 0.05). We conclude that both a cholinergic and an octreotide-sensitive noncholinergic pathway stimulate fasting sphincter of Oddi motility in the prairie dog. PMID- 1590400 TI - An abnormal rate of actin myosin cross-bridge cycling in colonic smooth muscle associated with experimental colitis. AB - Previous studies showed that colonic smooth muscle develops less contractile force to neurohumoral stimulation when associated with mucosal inflammation. This study evaluated 1) the Ca2+ dependence for colonic smooth muscle contraction, 2) the maximum velocity of muscle shortening (Vmax), and 3) changes in 20-kDa myosin light-chain (MLC) phosphorylation in distal circular colonic muscle from healthy rabbits and from rabbits with experimental colitis, induced by Formalin and immune complexes. The isometric tension of unskinned muscle stimulated with bethanechol or KCl was less (P less than 0.05) in animals with colitis compared with the control group. In saponin-skinned muscle, the amplitude of the maximal tension at [Ca2+] of 3 x 10(-7) M was decreased (P less than 0.05) in colitis animals (4.3 +/- 0.9 x 10(4) N/m2, n = 7) compared with healthy animals (10.5 +/- 2.4 x 10(4) N/m2, n = 6). However, the ED50 for Ca2+ stimulation was similar (P greater than 0.05) in both groups. When MLC was thiophosphorylated with ATP gamma S, the tension development was decreased in colitis (2.1 +/- 0.3 x 10(4) N/m2, n = 5; P less than 0.01) compared with normals (5.0 +/- 1.4 x 10(4) N/m2, n = 5). In healthy animals, phosphorylation of 20-kDa MLC increased rapidly to 51.2 +/- 3.1% within 15 s after stimulation and subsequently declined to 19.0 +/- 2.1% at 5 min. Vmax was maximal (0.14 Lo/s) 13 s after stimulation and declined before maximal active isometric stress. In colitis animals, the 20-kDa MLC phosphorylation (P less than 0.05) and the Vmax (P less than 0.01) were decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590401 TI - Further evaluation of the afferent nervous pathways from the rectum. AB - To evaluate the visceral afferents from the rectum, we recorded cerebral evoked potentials (EPs) in 26 healthy subjects after electrical stimulation of the rectum, pudendal nerve, and posterior tibialis nerve. We found two distinctly different EPs after rectal stimulation, with differences in latencies and pattern. In 13 subjects (group 1), the EP after rectal stimulation had multiple prominent peaks with early onset latencies ranging from 22 to 29 ms (mean 26 ms). In 13 subjects (group 2), the EP after rectal stimulation had a trifid configuration due to a very prominent negative peak between 97 and 108 ms (mean 101 ms) and longer onset latencies ranging from 50 to 61 ms (mean 55 ms). Latencies after pudendal nerve and posterior tibialis nerve stimulation were similar in the two groups. On further study, we found that both types of afferent pathways are present in the distal colon, since both types of EPs were found in the same subjects either in the rectum or in the rectum and sigmoid. We speculate that the early onset EP is a visceral pathway using the same afferents as the pudendal nerve because the early onset EP after rectal stimulation appears similar in number of peaks and interpeak latencies to EPs recorded after pudendal nerve stimulation, and the late onset EP is a visceral pathway using afferents along the pelvic nerve. Early onset EPs were also recorded after sigmoid stimulation, suggesting that both kinds of EPs are visceral afferents. PMID- 1590402 TI - Ultrasonic crystal measurement of blood volume changes in liver and spleen. AB - Two methods of measurement of splenic and hepatic vascular capacitance responses were compared in cats anesthetized with pentobarbital. For the spleen, measurements using ultrasonic crystals were compared with recordings of splenic weight. The cube of the relative change in thickness at one point on the longitudinal axis of the spleen was closely correlated with the overall change in spleen weight. For the liver, measurements by ultrasonic crystals were compared with plethysmographic recordings of liver volume. Individual measurements of cubed relative thickness did not correlate well with plethysmographic volume, and two sets of crystals on the same liver lobe gave different estimates of relative liver volume. However, averaged measurements for a group of animals showed similar means by the two methods. We conclude that ultrasonic crystals, when appropriately attached, can reliably monitor changes in splenic volume, but that for the liver, the variability in thickness responses at different sites on different livers is high. Unless a large number of observations are made, the results will be unreliable. PMID- 1590403 TI - Interaction between carbachol and vasoactive intestinal peptide in cells of isolated colonic crypts. AB - In a previous study [B. Biagi, Y.-Z. Wang, and H. J. Cooke, Am. J. Physiol. 258 (Gastrointest. Liver Physiol. 21): G223-G230, 1990], carbachol stimulated active chloride transport in rabbit distal colon, yet had no effect on the basolateral membrane potential (Vbl) of cells from isolated crypts from the same tissue. In the present study, crypt cells were first depolarized with vasoactive intestinal peptide (VIP; 1 x 10(-9) M) (control Vbl = -62 mV; VIP Vbl = -48 mV) and then exposed to carbachol in the presence of VIP. The VIP-induced depolarization of Vbl was completely reversed by carbachol (0.1 mM; repolarization to -65 mV). Similar repolarization was seen by applying carbachol to crypt cells depolarized by 10 mM aminophylline. Intracellular K+ activity (aiK), measured with K(+) selective microelectrodes, was 64.3 mM (concn = 85 mM), yielding a K+ equilibrium potential (EK+) of -76 mV. Neither carbachol nor VIP application caused significant changes in aiK. These results demonstrate the presence of cholinergic receptors on colonic crypt cells. The magnitude of the carbachol effect on Vbl is greater when Vbl is depolarized relative to EK+. The results are consistent with the hypothesis that carbachol acts by increasing basolateral K+ conductance, driving the cell toward the EK+. PMID- 1590404 TI - Human tryptase as a potent, cell-specific mitogen: role of signaling pathways in synergistic responses. AB - Mast cells are hypothesized to participate in processes leading to tissue fibrosis in human lung and skin. To explore the possible involvement of mast cell mediators in fibrogenesis, the mitogenic activity of mast cell tryptase from human lung was examined in vitro. The results indicate that human tryptase is a potent inducer of DNA synthesis in fibroblasts from multiple sources, including human lung. As demonstrated by mitogenic responses in fibroblasts, but not in vascular smooth muscle cells, tryptase is a mitogen with target cell specificity. Additionally, specificity is demonstrated by the differences in mitogenic activity of tryptase in comparison with thrombin, a structurally related mitogenic proteinase. Examination of the mitogenic effects of tryptase in the presence of other mitogens reveals synergy with mitogens that act through receptors coupled to intrinsic tyrosine kinases (insulin, epidermal growth factor, and basic fibroblast growth factor) or to G proteins (thrombin and serotonin). In the latter case, studies in Chinese hamster lung fibroblasts using specific receptor agonists and antagonists or receptor-transfected cell lines reveal a requirement for the activation of a G protein (Gi) negatively coupled to adenylate cyclase to act synergistically with tryptase. These data establish that human tryptase is a potent and specific mitogen in vitro and suggest that mitogenic signals generated by tryptase can interact synergistically with signals generated by both tyrosine kinase-coupled and G protein-coupled growth factor receptors. PMID- 1590405 TI - Human tracheobronchial epithelial cells direct migration of lung fibroblasts in three-dimensional collagen gels. AB - Normal airway morphogenesis and repair after injury depend in part on the interaction between the mesenchymal and epithelial cells in the tracheobronchial tree. We cultured human lung fibroblasts between layers of type I collagen gel and examined sections through these three-dimensional matrices to assess fibroblast migration. The migration assay used in these experiments allowed simultaneous assessment of directed and random fibroblast migration as well as cell number. We tested the hypothesis that human tracheobronchial epithelial (HTBE) cells direct the migration of fibroblasts. When fibroblasts were cultured alone, migration was nearly equivalent in the upper and lower collagen layers. When HTBE cells were plated on the upper collagen lattice, there was a net migration of fibroblasts toward the HTBE cells. The differential migration was evident early in culture but became maximal after 1 wk. Differences increased at higher HTBE cell inoculation densities. No epithelial chemokinetic or mitogenic influence was evident: total cell migration and total fibroblast number were not significantly different between the control and coculture sections. HTBE fibronectin production may contribute to directed migration because fibronectin, added to the upper lattice, reproduced a portion of the directed migration seen in coculture. Our data support the hypothesis that epithelial cells direct fibroblast migration. PMID- 1590406 TI - Comparative responses of brain stem and hippocampal neurons to O2 deprivation: in vitro intracellular studies. AB - Most mammalian neurons are known to be sensitive to oxygen availability, but the nature of the sensitivity is not well understood. Previous results have suggested that brain stem neurons may respond differently than cortical neurons during oxygen deprivation. We pursued this hypothesis by examining the time course of change in membrane potential (Vm) and input resistance (Rn) during periods of reduced oxygen availability in a tissue slice preparation. Since extracellular potassium is an important factor determining resting membrane potential, extracellular K+ activity, (K+o), was also measured. Adult rat neurons from three regions were recorded: hippocampal CA1 region, hypoglossal nucleus (XII), and dorsal vagal motor nucleus (DMNX). At the end of a 5-min hypoxic exposure, all neurons depolarized and this depolarization was greatest in XII (28.8 +/- 3.2 mV) compared with DMNX (17.8 +/- 3.7 mV) and CA1 (6.7 +/- 4.4 mV). K+o increased in all regions and was larger in DMNX (7.1 +/- 2.6 mM) and XII (5.3 +/- 2.1 mM) compared with CA1 (2.2 +/- 1.4 mM). During more severe oxygen deprivation (anoxia), neurons also depolarized at different rates with XII greater than DMNX greater than CA1. K+o increased markedly (28-36 mM) by 5 min into anoxia, and no statistical difference was observed between regions. From these results we conclude that 1) all cells tested were depolarized after 5 min of hypoxia; however, regional variability exists in the sensitivity to hypoxia; brain stem neurons depolarize faster than cortical neurons; 2) during anoxia, all brain stem and cortical neurons show a major depolarization, and 3) these differences in membrane potential cannot be solely attributed to changes in extracellular K+. PMID- 1590407 TI - An allelic variant of the 6A gene for human surfactant protein A. AB - Two human surfactant protein A (SP-A) cDNA clones (1A and 6A) encoding human SP-A genes have previously been identified and characterized by our laboratory. The present study was undertaken to assess potential heterogeneity in the 6A locus among specimens from white adults and infants with respiratory distress syndrome (RDS) as well as black adults. The entire and/or a portion of the published SP-A gene was amplified from different genomic DNAs using the polymerase chain reaction (PCR), cloned, and sequenced. The data revealed the presence of a variant (6A1) of the 6A gene with characteristics of the 1A gene. The most notable changes were a one-base change in exon 1 and an 11-base insertion in the 3' untranslated region (3'UT). Both changes are found in 1A gene. Analysis of the reverse-transcribed (RT) PCR products from lung mRNAs using 6A specific oligos showed that the 6A1 variant is transcribed. The prevalence of each SP-A allele was then assessed in a group of 20 Nigerian Blacks and 43 Whites (26 infants with RDS and 17 adults). Although the data did not reach statistical significance, a trend was shown where the 6A/6A genotype appeared with higher frequency in Blacks. PMID- 1590408 TI - Extracellular matrix synthesis and turnover by type II pulmonary epithelial cells. AB - Both type I and type II pulmonary epithelial cells contact the extracellular matrix (ECM). Type II cell-ECM interactions are bidirectional; they involve matrix-mediated modulation of type II cell differentiation, as well as cellular synthesis and deposition of ECM components. The present experiments examine the kinetics of accumulation of newly synthesized proteins in cell and matrix fractions from primary cultures of type II pneumocytes. Cycloheximide-sensitive incorporation of [3H]leucine into total protein of both the cell and ECM fractions was linear for 24-30 h, when steady-state labeling was reached and maintained to at least day 8. Over this interval, the cells enlarged but did not divide. Newly synthesized proteins recovered in the matrix fraction averaged 1-2% of those in the cells. Relative rates of radiolabeling of matrix proteins peaked at culture day 2 and increased in the absence of serum. In short-pulse studies, initial rates of protein synthesis were equal on culture days 1 and 3; this suggested that the steady-state labeling kinetics above reflected protein turnover. This was supported by rapid loss of radioactivity from the ECM after fresh type II cells were seeded on a prelabeled, cell-free matrix surface. Fresh or conditioned Dulbecco's modified Eagle's medium containing 10% fetal calf serum had little effect on matrix stability. These results demonstrate regulated deposition and turnover of a complex ECM by type II cells and provide a basis for further investigations of factors that control these processes. PMID- 1590409 TI - IL-1 beta and IL-6 gene expression in alveolar macrophages: modulation by extracellular matrices. AB - Interleukin-1 (IL-1) and interleukin-6 (IL-6) are two cytokines involved in a variety of host inflammatory reactions. The alveolar macrophage (AM), a predominant cell source for IL-1 and IL-6, exists in a microenvironment in which there are abundant extracellular matrix (ECM) components, and it is likely that ECM may participate in the inflammatory response in the lung by modulating the effector activities of AMs. To investigate this hypothesis, we cultured rat AMs on different substrates including plastic, collagen, and airways fibroblast derived ECM (fECM) and assessed IL-1 beta and IL-6 gene expression in these cells. Our study demonstrates that cytokine gene expression in AMs is affected by the conditions of culture. IL-1 gene expression is stimulated by adherence to plastic and exposure to endotoxin, whereas IL-6 mRNA is detectable only in the cells stimulated by endotoxin. Coating the plastic with collagen or fECM modifies cytokine gene expression. At early time points, collagen enhances gene expression. At later times (5 days), actin and cytokine gene expression are predominantly maintained in the endotoxin-stimulated cells cultured on fECM. These findings suggest an extracellular environment-directed mechanism of regulation of cytokine expression in alveolar macrophages. PMID- 1590410 TI - Effect of hypoxia on phospholipid metabolism in porcine pulmonary artery endothelial cells. AB - The effect of exposure of porcine pulmonary artery endothelial cells to hypoxic (0% O2) and normoxic (20% O2) conditions for 24 and 48 h on phospholipid metabolism was studied. Sonicates prepared from endothelial cells that were exposed to 24 h of hypoxia showed significant increases in phospholipase A1 (91%), phospholipase C (75%), and diacylglycerol lipase (57%) activities. Hypoxic exposure of cells for 48 h caused an increase in diacylglycerol lipase activity (54%) only. Hypoxia also caused significant decreases in ATP levels and ATP dependent arachidonyl coenzyme A (CoA) synthetase activity. Phospholipase A2, lysophosphatidylcholine acyltransferase, and diacylglycerol acyltransferase activities were not influenced by 24 or 48 h of hypoxia. When endothelial cells were prelabeled with [3H]arachidonic acid and then exposed to hypoxia, increased counts were recovered from the free fatty acid fraction of medium and from the cell fatty acid esters, lysophospholipids, diacylglycerols, and triacylglycerols. There was a concomitant decreased recovery of counts from cell phospholipids. These results indicate that hypoxic exposure of endothelial cells altered phospholipid metabolism by activating deacylation pathways and inhibiting reacylation via ATP-dependent arachidonyl CoA synthetase. PMID- 1590411 TI - Bumetanide-sensitive NaCl uptake in rabbit tracheal epithelial cells is stimulated by neurohormones and hypertonicity. AB - Loop diuretic-sensitive NaCl(K) cotransport plays a fundamental role in absorption and secretion of electrolytes in epithelial tissues. Cotransport activity was measured as uptake of 22Na, 36Cl, or 86Rb at 27 degrees C in isolated rabbit tracheal epithelial cells. Uptake of radiotracer was linear from 1 to 2 min after initiation of radiotracer transport. Bumetanide at 10 microM final concentration did not affect tracer uptake. The endogenous catecholamine l epinephrine and alpha 2-adrenergic agent clonidine increased sodium and chloride uptake at least 5.5-fold. Bumetanide blocked sodium uptake by 85% and chloride uptake by 72%. 86Rb uptake was not affected by l-epinephrine, clonidine, or bumetanide. The alpha 2-adrenergic antagonist yohimbine blocked the effects of l epinephrine and clonidine on 22Na and 36Cl uptake. In Ca(2+)-depleted transport medium, baseline levels of sodium and chloride uptake increased 3.8- and 2.4 fold, respectively, in a bumetanide-independent manner. Nevertheless, l epinephrine and clonidine induced a net stimulation of sodium and chloride uptake similar to that found in Ca(2+)-replete medium. This response was reduced by bumetanide and yohimbine. The Ca(2+)-elevating agent ionomycin increased bumetanide-sensitive sodium and chloride uptake 7.2- and 6.2-fold, respectively. Replacement of chloride with gluconate or sodium with N-methyl-D-glucamine in the extracellular medium inhibited l-epinephrine and clonidine-stimulated bumetanide sensitive sodium and chloride uptake, respectively. Osmotic shrinkage in hyperosmotic (500 mM NaCl with all other electrolytes at normal concentration) transport medium markedly increased bumetanide-inhibitable sodium and chloride uptake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590412 TI - Bioelectric properties of cultured epithelial monolayers from distal lung of 18 day fetal rat. AB - In vivo studies of fetal sheep suggest that the liquid present in the lumen of the lung throughout fetal life is derived from Cl- secretion by the pulmonary epithelium. Monolayer preparations of enriched epithelial cells from distal fetal rat (18-day gestation) lung, grown in serum-free media, were histologically similar to acinar (prealveolar) structures of fresh tissue. In Ussing chambers, basal transepithelial potential difference (PD), calculated equivalent short circuit current (Ieq), and transepithelial resistance (R) were 4.4 +/- 0.3 mV (matrix positive), 35.6 +/- 1.6 microA/cm2, and 120.0 +/- 4.0 omega cm2, respectively. Ouabain (10(-3) M) eliminated 57% of basal Ieq within 30 min, amiloride (10(-4) M) induced a 13% fall in Ieq, and phlorizin (10(-4) M) had no effect on bioelectric properties. Diphenylamine-2-carboxylate (DPC, 3 x 10(-3) M) inhibited Ieq by 50%. Bumetanide had no effect on baseline bioelectric parameters. The hyperpolarization that accompanied apical or bilateral replacement of Cl- and was enhanced by terbutaline suggested an apical Cl- permselectivity. Effects of Na+ replacement on amiloride-pretreated monolayers were consistent with Na(+)-dependent Cl- secretion or amiloride-insensitive pathways. Under these growth conditions, this preparation exhibits bioelectric characteristics that are compatible with Cl- secretion and Na+ absorption. The mechanism of Cl- secretion may be similar to that of airways but is uniquely bumetanide insensitive. PMID- 1590413 TI - Integrin receptors in the glomerulus: potential role in glomerular injury. AB - The extracellular matrix (ECM) exerts important effects on cell function that play a vital role in such diverse processes as embryogenesis, wound healing, cancer metastasis, and inflammation. Interactions between cells and matrix are mediated by a variety of cell surface receptors for different components of the ECM. The integrin family of matrix receptors, the best-studied group thus far, has already been shown to play an important role in cell-matrix and cell-cell interactions in other systems. More recently, the types of integrin receptors present in the glomerulus and on cultured glomerular cells have been defined, and their potential involvement in glomerular injury has been postulated. This review will summarize current knowledge of integrin receptors, their distribution in the kidney, cultured glomerular cell-matrix interactions that might play a role in modulating the glomerular cell response to injury, and the potential role of integrins and other glomerular cell matrix receptors as targets of injury in proteinuric lesions. PMID- 1590414 TI - Spatial and temporal expression of kallikrein and its mRNA during nephron maturation. AB - To determine the relationships between nephron maturation and the ontogeny of intrarenal kallikrein, the expression and distribution of kallikrein and its mRNA were examined in fetal, neonatal, and adult Sprague-Dawley rats. Kallikrein-like immunoreactivity was first expressed 1 day before birth in the upper limb of S shaped bodies. Immediately after birth, kallikrein immunostaining was present along the apical membranes of inner cortical distal tubules, whereas subcapsular less mature comma-shaped vesicles did not express kallikrein. After completion of nephrogenesis, kallikrein was also seen in the distal and connecting tubules of the outer cortex. In situ hybridization localized the kallikrein message in the distal tubules of inner cortical nephrons in newborns and outer cortex in adults. The transition from newborn to adult life was associated with six- and fourfold increase in renal kallikrein content and mRNA accumulation, respectively. We conclude that immature distal tubules have the transcriptional and translational capacity to express the kallikrein gene and protein and that the renal kallikrein gene is developmentally regulated. The spatial and temporal changes in intrarenal kallikrein expression during ontogeny are consistent with the hypothesis that the kallikrein-kinin system plays a role in the maturation of renal functions. PMID- 1590415 TI - Blockade of pressure natriuresis induced by inhibition of renal synthesis of nitric oxide in dogs. AB - To evaluate the participation of nitric oxide (NO) on pressure-induced natriuresis in pentobarbital-anesthetized dogs, renal perfusion pressure (RPP) was increased twice from 100 to 150 mmHg before and during the intrarenal administration of an NO-synthesis inhibitor, NG-nitro-L-arginine methyl ester (L NAME), while determining changes in glomerular filtration rate (GFR), renal blood flow (RBF), and urine sodium and water excretion. Before the inhibition of NO, the increase in RPP induced diuresis (5-fold) and natriuresis (4.2-fold) with no change in RBF or GFR. However, the intrarenal infusion of L-NAME (1 microgram.kg 1.min-1) blunted the diuretic and natriuretic responses without altering RBF or GFR. The infusion of the NO synthesis precursor L-arginine prevented the inhibitory effect that L-NAME exerted on the diuretic and natriuretic responses to the increase in RPP. These results indicate that the increase in RPP stimulates NO synthesis and suggest that NO might play an important role in the control of sodium and water excretion during acute changes in RPP. PMID- 1590416 TI - Intracellular pH in OK cells. II. Effects of temperature on cell pH. AB - Intracellular pH (pHi) is known to acidify as temperature rises. It has been proposed that this relationship reflects the temperature dependence of the dissociation constant of intracellular buffers. The purpose of this study was to evaluate whether H+ production and membrane acid/base transport events also contribute to the temperature dependence of pHi. This relationship was studied by means of the 490/450-nm fluorescence of 2',7'-bis(carboxyethyl)-5(6) carboxyfluorescein, to measure pHi of OK cells grown on cover slips and perfused in a thermostated chamber. As temperature was increased from 12 degrees C, pHi progressively acidified, until a precipitous and large alkalinization appeared at 40-45 degrees C. We specifically examined the range from 25 to 37 degrees C, over which pHi acidified by 0.32 units from 7.50 to 7.18. The three major components that regulate pHi in the OK cell were quantitated as follows: H+ production, H+ extrusion via Na(+)-H+ antiport, and the passive H+ leak from buffer to cell. Relative to the rate at 25 degrees C, acid production at 37 degrees C increased by 129% (3.82 +/- 0.78 vs. 8.76 +/- 1.12 mmol.l-1.min-1). The recovery of pHi after NH4Cl loading was used to measure the rate of Na(+)-H+ antiport, and in Na(+)-free depolarized cells the magnitude of passive H+ conductance through the leak pathway. Compared with the rate at 25 degrees C, at 37 degrees C the Na(+) H+ antiport increased by 26% (1.25 +/- 0.22 vs. 1.58 +/- 0.25 mmol.l-1.min-1) and the H+ permeability increased by 140% (0.005 +/- 0.001 vs. 0.012 +/- 0.003 cm/s).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590417 TI - Renal adaptation to low-phosphate diet in diabetic rats. AB - Insulin stimulates the Na(+)-Pi cotransport system in the brush-border membrane (BBM) of the renal proximal tubule, and an acute decrease in plasma insulin leads to a decrease in renal reabsorption of Pi. It has been proposed that insulin may play a role in the rapid renal adaptation to dietary deprivation of Pi. This hypothesis was tested using rats with low plasma insulin due to streptozotocin induced diabetes. Both control and diabetic rats were housed in metabolic cages and fed either a normal Pi diet or a low Pi diet for 3 days. At the end of the third day, BBM vesicles were prepared from renal cortex and Na(+)-Pi cotransport was measured. At the whole kidney level, diabetic rats showed a normal adaptive response. There was a prompt and marked decrease in urinary Pi excretion when the rats ate a low Pi diet. At the BBM level, however, the adaptive response was absent. There was no increase in Na(+)-Pi cotransport in diabetic rats fed low Pi diet. Treatment of diabetic rats with exogenous insulin before feeding low Pi diet restored the adaptive increase in Pi transport by BBM. Insulin appears to be required for the adaptation of proximal tubule Pi transport to low Pi diet. In the absence of this adaptation in proximal tubule BBM, a compensatory response in the kidney may produce an increase in Pi reabsorption in later segments of the nephron. PMID- 1590418 TI - CBF and oxygen metabolism in hemodialysis patients: effects of anemia correction with recombinant human EPO. AB - To investigate the effects of anemia correction with recombinant human erythropoietin (rhEPO) on both cerebral blood flow and oxygen metabolism in hemodialysis (HD) patients, the regional cerebral blood flow (rCBF), oxygen extraction (rOEF), and metabolic rate for oxygen (rCMRO2) were measured by positron emission tomography in five HD patients, and the data were compared with eight nondemented controls who had neither anemia nor uremia. In the HD patients, 1,500 U of rhEPO were administered intravenously three times a week to achieve a 10% increase in hematocrit (Hct) as an absolute value. Before rhEPO administration, the hemispheric rCMRO2 in HD patients was 1.48 +/- 0.09 (SE) ml.min-1.100 ml-1, which was significantly lower than that of 2.18 +/- 0.10 in the controls (P less than 0.01). In contrast, both rCBF and rOEF were significantly greater in the HD patients than the control, being 40 +/- 3 vs. 32 +/- 3 ml.min-1.100 ml-1 for rCBF (P less than 0.02) and 49 +/- 1 vs. 38 +/- 1% for rOEF (P less than 0.001). After treatment with rhEPO, Hct rose significantly from 21 +/- 1 to 31 +/- 1% in HD patients (P less than 0.001). There were significant reductions in both the hemispheric rCBF to 32 +/- 1 ml.min-1.100 ml-1 (P less than 0.01) and rOEF to 42 +/- 1% (P less than 0.01). However, the hemispheric rCMRO2 remained low at 1.58 +/- 0.06 ml.min-1.100 ml-1 even after rhEPO treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590419 TI - Effects of an acute saline infusion on fluid and electrolyte metabolism in humans. AB - Several hormonal systems participating in body fluid and electrolyte homeostasis were investigated in six healthy volunteers in a supine body position during a period of 9 days and nights. Under strictly controlled conditions, striking circadian rhythms were observed for plasma levels of vasopressin, renin, aldosterone, guanosine 3',5'-cyclic monophosphate, cortisol, and epinephrine. Nocturnal decreases and diurnal increases in urine flow rate and urinary excretion of electrolytes were observed and closely paralleled the urinary excretion of urodilatin. During 48 h after an acute isotonic saline infusion (2 liters within 25 min) and after a 48-h control experiment the urinary excretion of H2O and electrolytes, and simultaneously the alterations in endocrine systems participating in body fluid homeostasis, were determined. Urine flow and urinary electrolyte excretion rates were significantly increased during 2 days after the saline infusion. The largest increase in urinary fluid and electrolyte excretion was observed between 3 and 22 h postinfusion. These long-term changes were paralleled by altered H2O and Na balances and also by elevated body weights that returned to baseline values with an approximate half-life of 7 h. These data suggest that vasopressin, atrial natriuretic peptide, and catecholamines are unlikely to be of major importance for the renal response to this hypervolemic stimulus. The renin-aldosterone system was suppressed during 2 days postinfusion. This suppression correlated with the effects of saline load on Na excretion. However, the closest relation with Na excretion was observed for the kidney derived member of the atrial natriuretic peptide family, urodilatin, which was considerably increased during the long-term period up to 22 h postinfusion. Thus these data show that the human body in supine position requires approximately 2 days to regulate the amount of Na and H2O provided by an acute saline infusion. The data also suggest that urodilatin and the renin-aldosterone system might participate in the long-term renal response to an acute saline infusion and also in the mediation of circadian urinary excretion rhythms. PMID- 1590421 TI - Transport of beta-hydroxybutyrate and acetoacetate along rat nephrons: a micropuncture study. AB - The transport of ketone bodies across the luminal membrane of the nephron was studied by means of micropuncture techniques in rats in normal acid-base state. The concentration of beta-hydroxybutyrate (beta-HB) and acetoacetate (AcAc) in plasma, tubular fluid and urine was measured by an ultramicromethod using enzymatic cycling. At endogenous plasma ketone body concentration, approximately 80% of the filtered load of beta-HB and AcAc was reabsorbed in the proximal convoluted tubule, the remaining fraction being almost completely reabsorbed between the late proximal convoluted and the distal tubule; under these conditions, the urinary excretion of ketone bodies was less than 1% of the filtered load. A progressive elevation to steady-state levels of plasma beta-HB resulted in a progressive reduction of the fractional reabsorption of beta-HB and AcAc in the proximal convoluted tubule, which means that reabsorption of ketone bodies in this nephron segment is saturable. No net secretion of ketone bodies could be demonstrated along the nephron even at the highest plasma ketone body concentrations reached. In clearance experiments, the capacity of the rat kidney for reabsorbing both beta-HB and AcAc was found to be limited by a maximal tubular capacity (Tm). The data suggest that, in the young Wistar rat nephron, most of the reabsorption of ketone bodies is carrier mediated. PMID- 1590420 TI - Apolipoprotein gene expression in analbuminemic rats and in rats with Heymann nephritis. AB - The nephrotic syndrome results from altered glomerular permselectivity, causing urinary protein loss, reduced albumin concentration, oncotic pressure (pi), and hyperlipidemia. Hepatic lipid and apolipoprotein synthesis increases and lipoprotein catabolism decreases. Decreased lipoprotein catabolism follows the onset of proteinuria but is not associated with hereditary analbuminemia [Nagase analbuminemic rat (NAR)] if proteinuria is absent. We measured plasma apolipoproteins (apo) AI, B, and E levels, their mRNA concentrations in liver, and the transcription rate of each mRNA in rats with Heymann nephritis (HN) or NAR to determine which alterations occurred in NAR alone without proteinuria. Plasma apo AI, B, and E were increased in both HN and NAR. Cholesterol and apo AI were inversely proportional to pi and independent of urinary protein loss or the presence of albumin in plasma. In contrast, triglycerides (TGs) were significantly greater in HN and were increased out of proportion to apo B. The concentration of apo AI mRNA increased in liver of both HN and NAR as did apo AI transcription. Apo E mRNA increased in neither HN nor NAR, whereas apo B mRNA increased only in HN. Transcription of neither apo B nor E increased. Plasma apo AI levels are likely to be regulated transcriptionally at the level of protein synthesis, whereas plasma apo B and E levels are regulated either posttranscriptionally, at the level of protein catabolism, or at both sites. Lipoproteins rich in TG and poor in apo B appear after the development of proteinuria but not as a consequence of analbuminemia alone. The accumulation of TG-rich apo B containing lipoproteins in rats with HN may result from impaired lipolysis occurring as a consequence of proteinuria. PMID- 1590422 TI - Anti-Fx1A antibody recognizes a beta 1-integrin on glomerular epithelial cells and inhibits adhesion and growth. AB - Cell-matrix interactions play an important role in regulating cell growth and metabolic activity and potentially in maintaining the integrity of the glomerular filtration barrier. The effect of anti-Fx1A antibody (Ab), the pathogenetic Ab of passive Heymann nephritis, on the interaction of cultured rat glomerular visceral epithelial cells (GEC) with matrix components was examined in an effort to determine whether it affects cell adhesion. Affinity chromatography demonstrated that anti-Fx1A recognizes an alpha 3 beta 1-integrin-type matrix receptor on GEC. Anti-Fx1A inhibited the adhesion of GEC to several substrates (collagen IV approximately equal to collagen I less than laminin approximately equal to fibronectin) in a dose-dependent manner and produced reversible cell detachment and "rounding up" when added to adherent cells. Maximal inhibition of adhesion was similar with anti-Fx1A and anti-beta 1, and competition studies showed no additive effects between anti-Fx1A and anti-beta 1 in inhibiting adhesion, suggesting that the effect of anti-Fx1A on GEC adhesion is attributable to its anti-beta 1 activity. Anti-Fx1A Ab also inhibited the growth of GEC in culture without evidence of cytotoxicity, and cells resumed normal growth on removal of Ab. These studies suggest that anti-Fx1A Ab can bind to matrix receptors on GEC, resulting in inhibition of cell attachment and growth, as well as producing detachment of cells that are already adherent. Interference with GEC-glomerular basement membrane interactions in vivo might have significant effects on glomerular permeability to proteins. PMID- 1590423 TI - Cysteine oxidation by the postischemic rat kidney. AB - Renal levels of glutathione are markedly decreased during periods of renal ischemia due to catabolism to cysteine. We previously demonstrated that cysteine accumulates in the tissue as the thiol during ischemia, and resumption of blood flow causes a transient elevation of cysteine levels in the renal venous effluent and return of tissue cysteine levels to control values. In this study, the oxidation state of renal venous cyst(e)ine was determined. Although cysteine accumulated as the reduced thiol during ischemia, cysteine released into the renal vein upon blood reflow was found to be almost entirely in the disulfide form. To distinguish between oxidation of arterial cysteine and renal cysteine formed from ischemia-induced reduced glutathione (GSH) catabolism, a labeling procedure was developed to label kidney GSH with 35S without significant labeling of arterial plasma cyst(e)ine. With this procedure, the source of oxidized cysteine that appeared in the renal venous plasma after ischemia was identified as resulting from renal GSH catabolism. The data indicate that a rapid oxidative process occurs during the initial period of blood reflow to the postischemic kidney. After 35 min of ischemia, 3 mumol cysteine/g dry wt were released from the kidney and oxidized. Cysteine oxidation is also expected to generate oxygen centered free radicals. Pretreatment of animals with deferoxamine, a iron chelator, was without effect on the relative amount of venous cysteine in the oxidized form, arguing against a role for free iron in this oxidative process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590424 TI - Calcium-dependent inhibitory step in control of renin secretion. AB - The regulatory step for Ca(2+)- and calmodulin-dependent control of renin secretion was studied in rabbit renal cortical slices. Renin secretion was stimulated by adding the K(+)-H+ exchange ionophore nigericin or a weak base, benzylamine, to Ca(2+)-free incubation medium. Both nigericin and benzylamine can produce chemiosmotic swelling of acidic intracellular organelles in a pH gradient dependent manner. Swelling of renin secretory granules may account for the stimulatory effects of these two agents on renin secretion. The stimulation of renin secretion by each of these agents was prevented by including Ca2+ in the incubation medium. The inhibitory effects of Ca2+ were reversed by the calmodulin antagonist calmidazolium, suggesting that the Ca2+ inhibition may be mediated by calmodulin. However, when renin secretion was first stimulated by nigericin or benzylamine in Ca(2+)-free medium, subsequent addition of Ca2+ to the incubation medium failed to reverse the stimulation. These results therefore suggest that Ca2+ acting through calmodulin may exert its inhibitory effects on renin secretion by blocking an early step in the cellular events that lead to renin secretion such as pH gradient-dependent swelling of renin secretory granule. PMID- 1590425 TI - Glucose transporters of rat proximal tubule: differential expression and subcellular distribution. AB - In the late proximal tubule, glucose reabsorption progressively lowers the concentration of luminal glucose, and concentrative glucose influx increases to ensure complete glucose reabsorption. The change in glucose influx is effected by luminal Na(+)-dependent glucose transporters (Na(+)-GLUT), which exhibit higher Na(+)-to-glucose stoichiometric ratios in the late proximal tubule. In this work, the corresponding changes in the axial distribution of basolateral glucose efflux transporters (GLUTs) were examined. mRNAs encoding high-affinity facilitative basolateral transporter GLUT1, low-affinity GLUT2, and apical Na(+)-GLUT were identified in mixed populations of proximal convoluted and straight tubules. The organization of the cognate proteins was also appraised on Western blots. GLUT1 was present in glomeruli, proximal convoluted, and straight tubules, GLUT2 was only expressed in the proximal convoluted tubule, and Na(+)-GLUT was present in both proximal convoluted and straight segments. GLUT1 and GLUT2 were confined to the basolateral membrane, whereas Na(+)-GLUT was preferentially localized to the brush-border membrane. These data are consistent with the idea that glucose influx in early and late proximal tubule is achieved through Na(+)-GLUT, that GLUT1 and GLUT2 are responsible for glucose efflux in the early proximal tubule, and that in the late proximal tubule, where transcellular glucose flux is lower, only GLUT1 mediates glucose efflux. PMID- 1590426 TI - Time course and kinetics of proximal tubular processing of insulin. AB - The present study was undertaken to determine the time courses and kinetics of the subcellular processing of 125I-insulin in isolated and in vitro perfused proximal tubules. Morphometric analysis demonstrated well-preserved ultrastructure after 90 min of perfusion. After luminal perfusion for 90 min the absorption was constant with time and reached steady state within 5 min (177 +/- 7 fg.min-1.mm-1). Also the hydrolysis rate and tubular accumulation rate were constant and averaged 84 +/- 8 and 93 +/- 10 fg.min-1.mm-1, respectively. Free 125I appeared already within 5 min of perfusion and reached steady state within 10 min. From proximal tubules perfused with 125I-insulin for 30 min and chased for 60 min, a compartmental analysis revealed two compartments; half time (t1/2) for delivery of insulin to the lysosomes was determined to be 8.5 min, and t1/2 for lysosomal degradation was 72 min. The results demonstrated that internalization by endocytic invaginations, incorporation in endocytic vacuoles, fusion with lysosomes, and hydrolysis were rapid processes and reached maximum rates within few minutes. A significant transtubular transport of insulin to the peritubular compartment was determined to be a constant rate of 11.2 +/- 0.7 fg.min-1.mm-1. Perfusion of tubules with insulin at high concentrations in the perfusate revealed that the transport was dependent on the absorbed amount and not on the perfused load, compatible with transport through the cells and not via a paracellular mechanism. The intactness of the tight junctions was supported by the following: 1) [14C]inulin leak did not increase with time and 2) enzyme-free intercellular spaces were evident after perfusion for only 5 min with microperoxidase (mol wt of 1,700). The transported 125I-insulin was trichloroacetic acid precipitable and immunoprecipitable. PMID- 1590427 TI - Renal nerve effects on renal adaptation to changes in sodium intake during ovine pregnancy. AB - To assess the possibility of an enhanced role of renal nerves in the control of urinary sodium excretion (UNaV) and fluid homeostasis during pregnancy, urine output, UNaV, and urinary potassium excretion were assessed hourly for 3 days before and for 6 days after a step reduction in total daily sodium intake from 400 to 40 mmol. Studies were performed in normal conscious sheep (4 nonpregnant and 4 pregnant). Each animal was prepared with a divided bladder so that urine could be collected simultaneously from one normally innervated and one denervated kidney. In nonpregnant ewes, ratios of the rates of excretion by denervated vs. innervated kidneys for UNaV averaged 1.00 +/- 0.07 under steady-state conditions at high levels of sodium intake. This ratio was not different at the low-sodium intake state. In contrast, this ratio was 1.15 +/- 0.07 at high sodium intake and 1.13 +/- 0.03 at low sodium intake in pregnant ewes. The ratios at both steady state intake levels were different (P less than 0.05) between nonpregnant and pregnant sheep. During the transition between sodium intake states, these ratios were unchanged in nonpregnant animals, whereas pregnant animals exhibited peak ratios of 2.20 +/- 0.39 (P less than 0.05), indicating sodium wasting by the denervated kidneys. In summary, the data suggest that renal nerve activity may not be completely suppressed by high sodium intakes in pregnant sheep. Furthermore, the renal nerves have an enhanced influence on sodium conservation during and after the transition from high- to low-sodium-intake states during pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590428 TI - Osmolytes in renal medulla during rapid changes in papillary tonicity. AB - The effect of acute changes in extracellular tonicity on cell electrolyte concentrations at the renal papillary tip and on organic osmolytes in different kidney zones was studied using electron microprobe analysis and high-performance liquid chromatography in four groups of rats: controls, 1- or 4-h water diuresis, and 4-h water diuresis followed by 30-min deamino-[Cys1,D-Arg8]vasopressin (ddAVP). The sum of the papillary interstitial concentrations of Na, K, and Cl was reduced from 981 mmol/kg wet wt in controls to 318 mmol/kg wet wt after 4-h diuresis and increased after ddAVP to 840 mmol/kg wet wt. In papillary collecting ducts intracellular electrolytes fell from 225 to 156 mmol/kg wet wt after 4-h diuresis and rose to 268 mmol/kg wet wt (significantly higher than control) after ddAVP. Organic osmolytes [sum of glycerophosphorylcholine (GPC), betaine, myo inositol, and sorbitol] at the papillary tip decreased from 2,018 (control) to 1,037 mmol/kg protein after 4-h diuresis and did not increase after ddAVP. After ddAVP, cell P concentration, an index of cell GPC concentration, increased, indicating cell shrinkage. GPC concentration increased, indicating cell shrinkage. The results suggest that the concentrations of all osmoeffectors in papillary cells initially increase due to cell shrinkage in response to hypertonic stress. The higher intracellular ionic strength may be a signal for modulation of transport and metabolism of organic osmolytes. PMID- 1590430 TI - Growth hormone regulates ammoniagenesis in canine renal proximal tubule segments. AB - To determine whether growth hormone (GH) directly affects ammoniagenesis in the renal proximal tubule, ammonia production was measured in suspensions of isolated canine renal proximal tubule segments (IPTs) incubated with 2.5 mM L-glutamine and varying concentrations of human growth hormone (hGH). Ammonia production from IPTs significantly increased by nearly threefold in the presence of hGH (10(-6) M) at 60 min. This increase was dose dependent, with as little as 10(-9) M hGH significantly stimulating ammonia production. In addition, hGH enhanced glucose production when lactate, alanine, and succinate replaced L-glutamine as substrate. hGH significantly stimulated ammonia production when IPTs were incubated at alkalotic and neutral pH. The effect of hGH was lost at acidic pH. When hGH was added to IPTs incubated under Na(+)-equilibrated conditions, ammonia production was not different from control. hGH stimulated ouabain-sensitive Na(+) K(+)-adenosinetriphosphatase (ATPase) activity by 8.1 +/- 1.1% in basolateral membranes isolated from IPTs. hGH stimulation of proximal tubule ammonia production from L-glutamine occurs at physiological concentrations of hGH and when the extracellular-to-intracellular Na+ gradient favors L-glutamine transport. This effect is associated with an increase in basolateral Na(+)-K(+) ATPase activity. The data suggest a role for hGH in the regulation of renal acid base metabolism under physiological conditions in which increased net acid excretion is important. PMID- 1590429 TI - Temporal pattern of renin and aldosterone secretion in men: effects of sodium balance. AB - To investigate the pulsatile nature of basal and stimulated renin and aldosterone secretion, we sampled blood for plasma renin activity (PRA) and plasma aldosterone concentration at 10-min intervals for 24 h in nine normal supine human male subjects after equilibration in high- and low-sodium balance states. We evaluated serial hormonal measures by a quantitative waveform-independent deconvolution technique designed to compute the number, amplitude, and mass of underlying secretory bursts and simultaneously to estimate the presence and extent of basal secretion. For both PRA and aldosterone: 1) burstlike release accounted for greater than or equal to 60% of total secretion and tonic release for less than 40%; 2) there was an 80- to 85-min interpulse interval unchanged by sodium intake; 3) sodium restriction engendered an increase in plasma hormone concentrations by increasing the amount and maximal rate of hormone secreted per burst; 4) low dietary sodium also induced increases in basal hormone secretory rates, suggesting that there may be two regulatory processes driving renin and aldosterone secretion; and 5) PRA was significantly coupled to plasma aldosterone concentration by a 0-, 10-, or 20-min aldosterone lag time in both high- and low sodium balance. We conclude that both renin and aldosterone are released via a predominantly burstlike mode of secretion; PRA and plasma aldosterone concentrations are positively coupled by a short time lag (0-20 min); and sodium restriction achieves an increase in mean PRA and plasma aldosterone concentration by selective amplitude enhancement of individual hormone secretory bursts and by increased tonic (interburst) basal secretory rates. PMID- 1590431 TI - Changes in electrical properties of guinea pig smooth muscle membrane by experimental bladder outflow obstruction. AB - The changes in membrane electrical properties of guinea pig bladder smooth muscle following experimental bladder outflow obstruction were studied by means of an intracellular microelectrode technique. The results of this study can be summarized as follows. 1) Bladder outflow obstruction resulted in a threefold increase in bladder weight after 4-8 wk. 2) The resting membrane potential was unchanged with obstruction; however, the obstructed smooth muscle membrane was more quiescent, with less spontaneous electrical activity compared with control tissue. 3) The membrane constants, space constant and time constant, were both reduced in the obstructed bladders. 4) There was no detectable difference in membrane depolarization induced by high extracellular K+ solution between control and obstructed bladders. 5) Both the membrane depolarization induced by K(+)-free solution or ouabain-containing Krebs solution and ouabain-sensitive membrane hyperpolarization by K(+)-containing solution after application of K(+)-free solution were significantly increased in the obstructed bladders. 6) Low extracellular Cl- solution evoked greater membrane depolarization in obstructed bladders. These results suggest that bladder outflow obstruction results in suppression of the cell-to-cell transfer of electrical activity and activation of a membrane electrogenic Na(+)-K+ pump mechanism in guinea pig detrusor. PMID- 1590432 TI - Colocalization of GAPDH and band 3 (AE1) proteins in rat erythrocytes and kidney intercalated cell membranes. AB - Glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.2.12) (GAPDH) is a multifunctional protein that associates with the cytoplasmic face of intact human erythrocyte membranes. This association has been postulated to be critically dependent on the interaction of GAPDH with the highly acidic NH2-terminal domain of the principal integral membrane protein of the erythrocyte plasma membrane, the band 3 anion exchanger (AE1). This domain is not conserved in murine erythrocyte AE1 and is fully deleted in the alternatively spliced AE1 isoform that is expressed in the kidney. The lack of conservation of this domain has been proposed to explain the reported absence of GAPDH association with rodent erythrocyte membranes. To determine whether GAPDH could be associated with AE1 proteins in rodent cell membranes, specific rabbit antibodies to peptide sequences of rat GAPDH and mouse AE1 were used to immunolocalize these proteins in sequential semithin sections of rat erythrocytes and kidney medulla. In rat erythrocytes, GAPDH immunoreactivity was predominantly membrane associated and colocalized with AE1. In the kidney medulla, GAPDH was concentrated in the basolateral membrane of type A intercalated cells, where it colocalized with the alternatively spliced kidney form of AE1. GAPDH immunoreactivity was not detected in the plasma membrane of any other cell type in the kidney, indicating its predominant association with AE1-rich membranes. If this membrane interaction occurs via AE1 binding, then GAPDH must have binding sites in addition to those previously described for such binding in human AE1. PMID- 1590433 TI - Regulation of adrenal medullary and cortical blood flow. AB - Before 1986, little was known concerning regulation of blood flow to adrenal medulla and cortex. With the introduction of a radiolabeled microsphere methodology, which permitted independent measurement of blood flow to the two regions, it became apparent that medulla and cortex regulate blood flow independently and that both regions receive levels of blood flow considerably in excess of that required for nutrient delivery. It is likely that abundant blood flow serves to speed entry of adrenal secretory products into the systemic circulation. Coupling of blood flow with secretion is particularly apparent in medulla, where severalfold increases in blood flow occur during catecholamine secretion elicited by hemorrhage, hypoxia, and splanchnic nerve stimulation. Both catecholamine secretion and medullary vasodilation are neurally mediated. The two responses can be pharmacologically dissociated, suggesting possible direct innervation of adrenal vessels. However, morphological confirmation of vascular innervation is not available, and effects of released chromaffin cell products on adjacent vessels are also possible. In contrast to medulla, cortical secretory activity is not associated with altered blood flow. However, neural elements are found in close proximity to cortical vessels, and the cortical vasculature responds to changes in O2 tension and to a number of pharmacological agents. In addition, several studies indicate that cortical secretory activity can be modulated by changes in blood flow. The response of both vasculatures to pharmacological agents is, in many instances, different from responses observed in other vascular beds. These data indicate that the adrenal has evolved unique vasoregulatory mechanisms, either because vasoactive compounds are present in such high concentration, or because blood flow plays an important role in the secretory process. PMID- 1590434 TI - N omega-nitro-L-arginine and pulmonary vascular pressure-flow relationship in conscious dogs. AB - We investigated the effects of an inhibitor of nitric oxide (NO) synthesis, N omega-nitro-L-arginine (L-NNA), on the pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs. The L-arginine analogue L-NNA (20 mg/min for 60 min iv) had no effect on the baseline pressure-flow relationship. This result indicates that tonic release of endothelium-derived relaxing factor (EDRF), which is thought to be NO or a labile NO-generating molecule, is not responsible for low resting pulmonary vasomotor tone in conscious dogs. In contrast, L-NNA caused a leftward shift in the dose-response relationship to the thromboxane mimetic U-46619, indicating that the endogenous release of EDRF modulates the pulmonary vascular response to this vasoconstrictor. Finally, after preconstriction with U-46619, L-NNA abolished the pulmonary vasodilator response to bradykinin (1-10 micrograms.kg-1.min-1) but had no effect on the pulmonary vasodilator response to sodium nitroprusside (1-10 micrograms.kg-1.min-1). Thus EDRF does not appear to tonically regulate the baseline pulmonary vascular pressure-flow relationship in conscious dogs. However, EDRF does act to attenuate the magnitude of U-46619-induced pulmonary vasoconstriction. Moreover, the pulmonary vasodilator response to bradykinin is entirely mediated by EDRF in conscious dogs. PMID- 1590435 TI - Cerebrovascular reactivity to adenosine analogues in 0.6-0.7 gestation and near term fetal sheep. AB - During acute hypoxia, fetal sheep less than 0.7 gestation increase cerebral blood flow (CBF) relatively less than fetal sheep near term. We hypothesized that cerebrovascular reactivity to a hypoxic vasodilator metabolite such as adenosine might be diminished in immature fetuses. This study examined cerebral vasoreactivity to adenosine analogues in nine sheep fetuses less than 0.7 gestation (90-103 days) and nine near term (129-143 days). Fetuses were equipped in utero with a closed cranial window, and pial arterioles were studied by intravital microscopy. 5'-(N-ethylcarboxamido)-adenosine (NECA; 10(-9)-10(-5) M) and N6-cyclopentyladenosine (CPA; 10(-9)-10(-4) M) each caused a dose-dependent increase in arteriolar diameter that was attenuated in the presence of the adenosine receptor antagonist 8-phenyltheophylline (8-PT; 5 x 10(-6) M). Dose response curves to the agonists were similar for both age groups. NECA was a more potent vasodilator than CPA, in keeping with their affinity for the A2 receptor. Suffusion of 8-PT alone at less than 10(-5) M had no effect on arteriolar diameter. We conclude that adenosine is able to dilate fetal cerebral arterioles as young as 0.6 gestation by acting at an A2 receptor, although resting tone is not influenced by adenosine. The immature fetal sheep CBF response to hypoxia is not attributable to undeveloped vasoreactivity to adenosine. PMID- 1590436 TI - L-NMMA in brain microcirculation of mice is inhibited by blockade of cyclooxygenase and by superoxide dismutase. AB - As previously reported, NG-monomethyl-L-arginine (L-NMMA) constricted pial arterioles, inhibited dilation of pial arterioles by acetylcholine (ACh) or L arginine (L-Arg), and enhanced platelet adhesion/aggregation at sites of endothelial damage. However, all of these effects were inhibited by local application of 20 micrograms/ml indomethacin (Indo). When 100 micrograms/ml acetylsalicylic acid were used instead of Indo, the acid also blocked the effects of L-NMMA. Superoxide dismutase (SOD; 50 U/ml) blocked the constriction produced by L-NMMA and also blocked the constriction produced by N omega-nitro-L-arginine (NNA). SOD also prevented L-NMMA from blocking dilation by ACh. SOD itself had no effect on diameter or on the response to ACh, norepinephrine, or BaCl2. The effects of L-NMMA and of Indo were also selective. Thus L-NMMA did not inhibit dilation by prostacyclin or bradykinin, and Indo did not inhibit dilation by prostacyclin. Indo did not interfere with the ability of arginase to enhance platelet adhesion/aggregation or with the ability of ACh or L-Arg to inhibit adhesion/aggregation. We conclude that in mouse cerebral microcirculation the ability of L-NMMA and NNA to constrict arterioles, the ability of L-NMMA to inhibit dilation by ACh or L-Arg and the ability of L-NMMA to enhance platelet adhesion/aggregation are all related to interference with phenomena dependent on "classical" endothelium-derived relaxing factor (EDRFACh). However, in this preparation the action of L-NMMA or NNA may not be due to competitive inhibition of the enzyme producing EDRFACh from L-Arg. Rather, L-NMMA and NNA appear to activate cyclooxygenase with resultant production of superoxide, which inactivates EDRFACh. PMID- 1590437 TI - Role of calcitonin gene-related peptide in capsaicin-induced gastric submucosal arteriolar dilation. AB - The response of gastric submucosal arterioles to topical (submucosal) application of calcitonin-gene-related peptide (CGRP) or capsaicin with and without the human CGRP antagonist, hCGRP-(8-37), was studied using in vivo microscopy. CGRP (10( 11) to 10(-8) M) induced dose-dependent dilation. Topical treatment with hCGRP(8 37) (10(-6) M, for 10 min) caused a significant decrease in basal arteriolar diameter from 33 +/- 2 to 27 +/- 2 microns. hCGRP(8-37) did not alter acetylcholine- or adenosine-induced vasodilation but did significantly reduce CGRP 10(-8) M vasodilation from 97.3 +/- 10.1 to 15.9 +/- 4.4% of the maximal response. Topical capsaicin (10(-9) M to 5 x 10(-7) M) induced dose-dependent arteriolar dilation. This vasodilation was markedly attenuated by hCGRP(8-37). Selective ablation of capsaicin-sensitive sensory neurons nearly completely inhibited capsaicin-induced vasodilation, suggesting that this vasodilation is primarily neurogenic in origin. We conclude that 1) topical application of capsaicin stimulates capsaicin-sensitive sensory neurons and induces dose dependent arteriolar dilation; 2) this vasodilation is mediated in part by CGRP; and 3) CGRP may be involved in modulating the basal tone of gastric resistance vessels. PMID- 1590438 TI - Regional atrial distensibility. AB - We studied 12 open-chest dogs to determine whether there are regional differences in left atrial distensibility. Sonomicrometer crystal pairs were used to measure the anteroposterior diameters of the left atrial body and appendage simultaneously over a wide range of intracardiac pressures and volumes obtained by intravenous saline infusion. Left atrial pressure-natural strain data for the body and appendage were fitted to an exponential function. The mean coefficient of the left atrial monoexponential pressure-strain relationship was greater for the body than appendage (3.1 +/- 1.1 vs. 1.9 +/- 0.7 mmHg, P less than 0.01). The Y-intercepts were not significantly different (5.2 +/- 1.7 vs 4.9 +/- 1.8 mmHg). The maximum minus minimum left atrial dimension, an index of the reservoir function of the atrium, increased with volume infusion in both the body and appendage and was significantly greater in the appendage than body at each level of left atrial pressure. Similarly, atrial systolic shortening fraction increased with volume infusion, and regional shortening was greater in the appendage than the body at each level of left atrial pressure. We conclude that regional differences in atrial distensibility exist in vivo and may play an important role in modulating systolic and diastolic function of the left atrium. PMID- 1590439 TI - Passive effect of reduced cardiac function on splanchnic intravascular volume. AB - It has been hypothesized that lowered cardiac output due to heart failure results in passive redistribution of intravascular volume from the peripheral circulation to the central circulation and that this redistribution acts to support cardiac output. To test this hypothesis, acute heart failure was induced by rapid atrial pacing to raise heart rate from 148 +/- 6 to 232 +/- 1 beats/min for 5 min, while splanchnic intravascular volume was assessed with radionuclide imaging in eight anesthetized pigs that had undergone prior carotid denervation and vagotomy. Cardiac output decreased from 3,350 +/- 410 to 2,170 +/- 290 ml/min (P less than 0.001), mean arterial pressure decreased from 103 +/- 5 to 84 +/- 4 mmHg (P less than 0.001), left atrial pressure increased from 5.9 +/- 0.6 to 10.8 +/- 0.9 mmHg (P less than 0.001), right atrial pressure increased from 2.4 +/- 0.5 to 4.8 +/- 0.9 mmHg (P less than 0.001), total splanchnic intravascular volume did not change (0 +/- 2 ml), splenic intravascular volume decreased 11 +/- 3% (P less than 0.001), hepatic intravascular volume increased 12 +/- 2% (P less than 0.001), and mesenteric intravascular volume did not change (-3 +/- 2%). Thus, when cardiac output is lowered with pacing-induced acute heart failure, lowered perfusion pressure acts to lower splenic intravascular volume and increased central venous pressure acts to increase hepatic intravascular volume; however, total splanchnic intravascular volume does not decrease to support cardiac filling and cardiac output. PMID- 1590440 TI - EDRF inhibition augments pulmonary hypertension in intact newborn lambs. AB - There is increasing evidence that resting pulmonary vascular tone is mediated by the release of endothelium-derived relaxing factors (EDRF). However, the importance of EDRF release during pulmonary hypertension is unknown. Therefore, in eight newborn lambs we studied the effects of both N omega-nitro-L-arginine (an inhibitor of EDRF synthesis) and L-arginine (a precursor of EDRF synthesis) during pulmonary hypertension induced either by the intravenous infusion of U 46619 (a thromboxane A2 mimic) or by hypoxia. After pretreatment with N omega nitro-L-arginine, the increases in pulmonary arterial pressure produced by U 46619 (102.0 +/- 34.9% vs. 144.8 +/- 28.6%, P less than 0.05) and by hypoxia (35.6 +/- 17.3% vs. 91.4 +/- 24.8%, P less than 0.05) were significantly augmented. However, after pretreatment with L-arginine, the increases in pulmonary arterial pressure produced by U-46619 (107.0 +/- 21.4% vs. 62.6 +/- 22.6%, P less than 0.05) and hypoxia (44.3 +/- 18.3% vs. 9.2 +/- 11.7%, P less than 0.05) were significantly attenuated. These results suggest that during pulmonary hypertension, EDRF is released to limit the increase in pulmonary arterial pressure and that L-arginine availability becomes rate limiting for further EDRF synthesis and release. PMID- 1590441 TI - Baroreflex modulation of sympathetic outflow during physiological increases of vasopressin in humans. AB - Two studies were carried out to determine whether vasopressin influences the baroreceptor reflex of humans. In protocol 1, eight healthy subjects received sequential infusions of nitroprusside and phenylephrine to alter baroreceptor input. Muscle sympathetic nerve activity (SNA) was recorded to assess baroreceptor reflex modulation of efferent vasoconstrictor drive. Baroreceptor sensitivity (slopes) of the relationship between systolic pressure and R-R interval (cardiac baroslopes) and slopes relating muscle SNA to diastolic pressure were not altered during subpressor infusions of vasopressin, which raised basal plasma levels to 19 +/- 6 and 26 +/- 6 (mean +/- SE) pg/ml. A second protocol (n = 10 subjects) compared the reflex inhibition of SNA and heart rate produced by incremental pressor doses of phenylephrine and vasopressin. The calculated cardiac and sympathetic baroreflex gains did not differ between pressor agents. However, immediately following the peak dose of vasopressin (which elevated plasma levels to 35 +/- 3.6 pg/ml), reflex sympathoexcitation produced by unloading baroreceptors (with a bolus of nitroprusside) was significantly enhanced compared with an identical stress initiated at peak phenylephrine infusion. Thus increased levels of vasopressin ranging from 19 to 26 pg/ml did not alter cardiac or sympathetic baroreflex responses in humans. Higher levels of vasopressin may enhance the sympathetic response to unloading of baroreceptors. PMID- 1590442 TI - Effect of dietary n-3 fatty acids on cerebral microcirculation. AB - The purpose of these studies was to determine the effects of dietary n-3 fish oil on cerebrovascular reactivity and cerebrospinal fluid prostaglandin levels. Adult rabbits (n = 30) received fish oil (200 mg/kg eicosapentaenoic + 143 mg/kg docosahexaenoic acid), corn oil, or water by daily gavage for 6 wk and were then tested for their pial arteriolar diameter response to topical acetylcholine, bradykinin, or systemic asphyxia using the cranial window technique. Plasma and platelet fatty acids were measured by gas chromatography. Cerebrospinal fluid prostaglandin E and serum thromboxane B2 were measured by radioimmunoassay. n-3 Fatty acids were enriched in the plasma and platelets of the fish oil group (P less than 0.05). Serum thromboxane B2 was decreased by 31% in the fish oil group (P less than 0.05). The diameter response to acetylcholine and asphyxia was the same in all groups; however, the dilator response to bradykinin, which is known to be mediated by oxygen radicals, was significantly diminished in the fish oil group (P less than 0.05). Cerebrospinal fluid prostaglandin E concentration increased in response to acetylcholine, bradykinin, and asphyxia; however, the percent increase was less in the fish oil group. In summary, dietary n-3 fatty acids, which are purported to decrease heart disease, appear to selectively affect cerebral arteriolar reactivity, which is normally dependent on cyclooxygenase metabolism of arachidonic acid and formation of vasoactive oxygen radicals. PMID- 1590443 TI - Phasic and 24-h blood pressure control by endothelium-derived relaxing factor in conscious dogs. AB - The effects of blocking endothelium-derived relaxing factor (EDRF) on 24-h blood pressure and heart rate (HR) were examined in six conscious freely moving foxhounds. The hypothesis tested was that shear stress-dependent EDRF release acts as a physiological blood pressure buffer. Telemetry recordings were obtained before and after the administration of the false substrate for EDRF synthesis NG nitro-L-arginine (L-NNA, 16.5 +/- 2 mg/kg body wt iv). In response to L-NNA, mean arterial blood pressure (MAP) increased from 116 +/- 5 to 134 +/- 5 mmHg (P less than 0.01) and HR decreased from 97 +/- 6 to 68 +/- 3 beats/min over the entire 24-h period (P less than 0.01). The overall variability of MAP (as indicated by SD of frequency distribution) increased modestly from 9.5 +/- 0.4 to 11.7 +/- 1.1 mmHg (P less than 0.05). A sequential spectral analysis of blood pressure showed a 2.1-fold increase of power in the frequency range of 0.01-0.5 Hz (P less than 0.05) after L-NNA was given. In conclusion, blockade of EDRF led to a sustained hypertension throughout the whole 24-h recordings. Furthermore, EDRF acted as a physiological blood pressure buffer in the frequency range below 0.5 Hz. PMID- 1590444 TI - Epicardial sites for vagal mediation of sinoatrial function. AB - The posterior atrial fat pad (PAFP) has been described as the probable anatomic location of parasympathetic ganglia mediating sinoatrial (SAN) and atrioventricular nodal function in the mammalian heart. This contrasts with recent localizations of such control elements in the pulmonary vein fat pad (PVFP) and in fatty tissues overlying the junction of inferior vena cava-inferior left atrium (IVC-ILA), respectively. Short bursts (5-8 pulses/burst, 3 bursts/train) of electrical current (1-16 Hz, 400 ms, 1-5 mA) applied directly to the ventral right atrial epicardium via a concentric bipolar electrode (separation 0.3-0.6 mm) during the atrial muscle refractory period, activated subepicardial postganglionic pathways from PVFP and entering the SAN; identical stimulation of dorsal right atrial epicardium between PAFP and SAN excited few or no fiber pathways controlling SAN discharge rate or patterns. In a second series of experiments, injection of a neuronal marker (Fast Blue) into and around SAN, with time (5-10 days) allowed for retrograde transport, resulted in staining of many soma in PVFP but none in IVC-ILA or PAFP. These data strongly affirm the primary, and perhaps exclusive, localization of ganglia that mediate parasympathetic regulation of SAN function in PVFP of the dog's heart, with little or no such participation by ganglia within PAFP or IVC-ILA. PMID- 1590445 TI - Effect of fasting and refeeding on mesenteric autoregulation in conscious rabbits. AB - To determine whether feeding improves the efficacy of mesenteric autoregulation in conscious animals, rabbits were instrumented with pulsed-Doppler flow probes on the superior mesenteric artery and distal abdominal aorta to record mesenteric and hindquarters blood flow velocity. Hydraulic occluders were placed on the abdominal aorta (just below the celiac artery) and the thoracic vena cava to vary mesenteric and hindquarters arterial pressure (MAP), which was monitored via a catheter positioned in the distal abdominal aorta. Heart rate (HR) and lumbar sympathetic nerve activity (LSNA) were monitored as indexes of sympathetic nervous system activity. Pressure-velocity curves were obtained by aortic and caval occlusions on two consecutive days; first after a 24-h fast and after approximately 24 h of ad libitum refeeding. In the fed state, mesenteric velocity was significantly increased and MAP was decreased slightly; the slight decrease in MAP was counteracted by significant increases in HR and LSNA, whereas hindquarters perfusion was unchanged. The mesenteric and hindquarters pressure velocity curves were all highly linear (r greater than or equal to 0.9) and showed no evidence of autoregulation in the fasted or fed state when pressure was changed by either the aortic or the caval occlusions. We conclude that autoregulation plays a minor role in the short-term regulation of mesenteric blood flow in the conscious rabbit. PMID- 1590446 TI - Gadolinium and mechanotransduction of rat aortic baroreceptors. AB - The cellular mechanisms enabling baroreceptors to transduce wall distortion into axonal discharge are unknown but might involve stretch-activated ion channels. Gadolinium (Gd3+, 10 microM) blocks stretch-activated channels in several preparations. Here we tested Gd3+ effects on discharge responses of 15 single fiber baroreceptors in vitro. We simultaneously measured discharge, pressure, and aortic diameter at Gd3+ concentrations from 0.001 to 400 microM. High levels of Gd3+ added to a bicarbonate-buffered perfusate (Krebs) slightly shifted the pressure-discharge relation (less than 4 mmHg, n = 3, P = 0.01) without affecting slope or discharge frequency at threshold. Gd3+ in Krebs variably altered the pressure-diameter relation. Because 500 microM Gd3+ produced visible precipitate in Krebs, we tested Gd3+ in a simpler perfusate using N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid (HEPES). Gd3+ in HEPES (n = 10) induced minor, but statistically significant, average increases in threshold (less than +5-7%) and no changes in gain. However, prolonged HEPES exposure alone (n = 2) produced similar shifts. Electron microscopy verified that Gd3+ diffused from the lumen to reach extracellular locations near baroreceptor endings. We conclude that 1) HEPES perfusate alone reversibly depresses baroreceptor discharge and 2) Gd3+ has no direct effects on baroreceptors. Thus it appears that aortic baroreceptor mechanotransduction must utilize a different class of stretch-activated ion channels. PMID- 1590447 TI - Phasic characteristics of arterial inflow and venous outflow of right ventricular myocardium in dogs. AB - To clarify the characteristics and causes of phasic blood flow in coronary circulation of the right ventricle we measured blood velocities in peripheral portions of the right coronary artery and vein in dogs under three conditions: control, transient pulmonary stenosis, and isoproterenol administration. An optical fiber sensor of a laser Doppler velocimeter was fixed onto the vessels (150-500 microns OD) with cyanoacrylate. The phasic pattern of distal arterial velocity was compared with the proximal velocity in the right coronary artery measured with an ultrasound pulsed Doppler velocimeter. Systolic-to-total velocity area ratio in the small epicardial artery [0.38 +/- 0.03 (SE)] was found to be smaller than in the large epicardial artery (0.51 +/- 0.02, P less than 0.01), indicating a capacitive filling of the epicardial artery during systole. The velocity waveform in small right coronary veins was predominantly systolic; i.e., it increased with a rise of right ventricular pressure and decreased with right ventricular relaxation. Comparison of the waveforms during isoproterenol infusion and pulmonary stenosis indicates that contraction of the ventricle is more important than right ventricular systolic pressure in retarding arterial inflow and accelerating venous outflow. PMID- 1590448 TI - Diltiazem restores cardiac output and improves renal function after hemorrhagic shock and crystalloid resuscitation. AB - Although calcium antagonists produce salutary effects after shock and ischemia, it is unknown whether such agents restore the depressed cardiac output (CO) and renal function in a nonheparinized model of trauma-hemorrhage and resuscitation. To study this, rats underwent a midline laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mmHg until 40% of the maximum bleedout was returned in the form of Ringer lactate (RL). They were then resuscitated with four times the volume of shed blood with RL over 60 min. Diltiazem (400 micrograms/kg body wt) or an equal volume of saline was infused intravenously over 95 min. This infusion was started during the last 15 min of resuscitation. CO was determined by indocyanine green dilution. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance, and cortical microcirculation was examined by laser Doppler flowmetry. Results indicate that crystalloid resuscitation alone transiently restored but did not maintain CO after hemorrhage. Diltiazem infusion in conjunction with crystalloid resuscitation, however, restored and maintained CO and cortical microcirculation. Although GFR decreased in both groups, the values in diltiazem-treated animals were significantly higher than those in the sham-operated animals. Furthermore, diltiazem markedly decreased tissue water content. Thus diltiazem appears to be a promising adjunct in the treatment of hemorrhagic shock even in the absence of blood resuscitation. PMID- 1590449 TI - Dietary Na, age, and baroreflex control of heart rate and renal sympathetic nerve activity in rats. AB - Heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to ramp changes in blood pressure (BP) by (de)pressor agents and to acute volume expansion were recorded in conscious young, mature, and old Wistar rats maintained for 4 wk on diets containing low, control, or high dietary Na. Both HR and RSNA responses to BP increases or decreases were attenuated on low-Na diet compared with control Na diet. On high-Na diet, HR responses to BP changes and RSNA responses to BP increases were also attenuated, but in contrast the excitatory response of RSNA to BP decreases was augmented. The inhibitory RSNA response, but not the HR response, to volume expansion was significantly attenuated in young rats on high-Na diet but not on low-Na diet. The effects of both low and high dietary Na on HR and RSNA responses were most marked in young rats, less in mature rats, and even less in old rats. These results indicate a discordance of high dietary Na-induced changes in HR vs. RSNA control by the arterial and cardiopulmonary baroreflex, which is suggestive of central mechanisms affected by dietary Na. The developing nervous system appears to be the most responsive to dietary Na. PMID- 1590450 TI - Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury. AB - Differential recovery of prostacyclin and endothelium-derived relaxing factor after vascular injury. Am. J. Physiol. 262 (Heart Circ. Physiol. 31): H1449 H1457, 1992. The recovery of prostacyclin (prostaglandin I2, PGI2) synthesis and endothelium-derived relaxing factor (EDRF) activity, as demonstrated by acetylcholine (ACh)-induced relaxation, by rabbit aorta was examined up to 8 wk after balloon catheter-induced injury. Following injury, basal 6-keto-PGF1 alpha formation was decreased acutely; however, after 3 wk it was not different from control. Arachidonic acid-stimulated 6-keto-PGF1 alpha formation was decreased, returning to control levels at 3 and 8 wk for thoracic and abdominal aorta, respectively. ACh-induced relaxation did not return to control levels over the 8 wk study. Initiation of reendothelialization with a layer of hyperplastic endothelial cells overlying subendothelial fibrosis and intimal hyperplasia were present at 2-3 wk. Intimal hyperplasia appeared 2 wk after injury and progressed throughout the period of the study. These data indicate that following balloon catheter-induced injury the formation of both PGI2 and EDRF is reduced and that recovery follows a differential time course. In addition, the recovery of PGI2 formation did not coincide with the attenuation of intimal hyperplasia, whereas the relationship between EDRF formation and intimal hyperplasia is uncertain. PMID- 1590451 TI - Effects of birth-related stimuli on L-arginine-dependent pulmonary vasodilation in ovine fetus. AB - To determine the effects of birth-related stimuli on L-arginine-dependent vasodilation or nitric oxide (NO) activity in the perinatal lung, we studied the fetal pulmonary vascular effects of nitro-L-arginine (L-NA), a specific inhibitor of NO formation, during 1) mechanical ventilation without altering fetal blood gas tensions; 2) administration of high oxygen concentrations; and 3) increased flow or shear stress. In the first protocol, 13 late-gestation fetal lambs were ventilated with low fraction of inspired oxygen concentration (FIO2 less than or equal to 0.10) for 60 min after infusion of L-NA or saline into the left pulmonary artery (LPA). In control animals, LPA flow steadily increased during 60 min of ventilation. With L-NA treatment, the rise in flow and decrease in total pulmonary resistance (TPR) were reduced 67% (P less than 0.001 vs. control) and 28% (P less than 0.01 vs. control), respectively. Subsequent ventilation with high FIO2 (1.00) decreased mean pulmonary arterial pressure (PAP) in control but not in L-NA-treated animals. TPR remained fourfold greater in L-NA-treated animals than in control animals (P less than 0.001). In the second protocol, with partial compression of the ductus arteriosus, LPA flow increased 300% and TPR decreased 61% over 30 min. After L-NA treatment the rise in blood flow and decrease in TPR was markedly attenuated (P less than 0.001). We conclude that the perinatal pulmonary vasodilator response to ventilation without changing arterial oxygen tension and ventilation with increased oxygen tension are modulated by NO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590452 TI - Effect of microvascular rarefaction on tissue oxygen delivery in hypertension. AB - A mathematical model of oxygen transport in tissue was used to analyze the effects of microvessel rarefaction and nonhomogeneous oxygen consumption on tissue oxygen distribution. The model was based on the diffusion equation with a nonhomogeneous consumption term. Solutions were computed for several configurations of vessel and oxygen sink distributions on a finite domain using the finite element method. A microcirculatory unit consisting of a tissue slice of 100-microns depth and 40-microns width was chosen. Symmetry boundary conditions were applied so that the entire tissue consisted of a series of such microvascular units placed side by side. The boundary condition at the surface of the unit was chosen to simulate a tissue suffusion experiment in which the suffusion oxygen was varied from 0 to 37 mmHg. Results of the model, which were compared with direct measurements with oxygen microelectrodes, indicate that vascular oxygen delivery strongly dominates the tissue oxygen field for suffusion PO2 values of less than 20 mmHg, whereas above this level tissue oxygen is dominated by the suffusion PO2. Reduction of vessel density within the tissue was found to have the largest effect on tissue oxygen levels at low suffusion oxygen. Finally, under some configurations of oxygen sources (vessels) and sinks (mitochondria), extremely low PO2 levels may exist within the area of high consumption, which could limit the metabolic activity of the tissue. PMID- 1590454 TI - Adenosine modification of energy substrate use in isolated hearts perfused with fatty acids. AB - The objective of this study was to determine the effect of adenosine on overall myocardial substrate utilization and mechanical function in isolated working rat hearts. Hearts were perfused with Krebs-Henseleit buffer containing 11 mM glucose (no fat) or with 11 mM glucose and 0.4 mM palmitate (normal fat). Steady-state rates of glycolysis, glucose oxidation, and fatty acid oxidation were measured by determination of quantitative 3H2O and 14CO2 production from radiolabeled substrates. The ratio of glycolysis (6.07 +/- 0.57 mumol.min-1.g dry wt-1) to glucose oxidation (3.12 +/- 0.28 mumol.min-1.g dry wt-1) under no fat conditions was 2:1. The addition of palmitate per se decreased glucose oxidation (to 0.81 +/ 0.09 mumol.min-1.g dry wt-1) and increased the glycolysis-to-glucose oxidation ratio to 6:1. Adenosine (100 microM) reduced this ratio to 3:1 by decreasing glycolysis (to 3.75 +/- 0.32 mumol.min-1.g dry wt-1) and increasing glucose oxidation (to 1.28 +/- 0.18 mumol.min-1.g dry wt-1) in the presence of palmitate. Steady-state palmitate oxidation rates were not altered by adenosine. Adenosine increased efficiency (work performed per unit O2 consumed) of spontaneously beating hearts but had no effect in paced hearts. These effects of adenosine on glucose metabolism may explain the beneficial actions of adenosine during reperfusion post ischemia. PMID- 1590453 TI - Inhibition of endothelium-derived relaxing factor-dependent circulatory control in intact rats. AB - The effects of the endothelium-derived relaxing factor (EDRF) inhibitors NG monomethyl-L-arginine (L-NMMA) and methylene blue (MB) on resting hemodynamics and responses to vasodilators were studied in the intact rat anesthetized with pentobarbital sodium. L-NMMA infusions (100 mg/kg) significantly increased mean blood pressure by 48%; this effect was rapidly reversed by L-arginine (300 mg/kg). MB (50 mg/kg) decreased mean blood pressure by 24%. Both MB and L-NMMA significantly attenuated the vasodepressor responses to acetylcholine, ATP, and adenosine. By use of radiolabeled microspheres, it was determined that the blood pressure increase after L-NMMA was due to a marked increase in systemic vascular resistance (SVR; from 1.3 +/- 0.1 to 3.1 +/- 0.3 mmHg.ml-1.min-1) and decreased cardiac output. L-NMMA increased vascular resistance in brain, cerebellum, skin, skeletal muscle, ear, white and brown fat, kidney, spleen, hepatic artery, and gastrointestinal tract. Flow decreased in the skin, kidneys, ear, white and brown fat, gastrointestinal tract, portal venous circulation, and liver in response to L-NMMA. In contrast, MB decreased heart rate, blood pressure, and SVR significantly. MB increased blood flow and decreased vascular resistance in several organs, including the brain, and skeletal muscle. These results indicate that both MB and L-NMMA can inhibit agonist-induced EDRF-mediated vasodepressor responses. However, inhibition of agonist-induced responses did not predict the general and regional hemodynamic responses to L-NMMA or MB infusion. PMID- 1590455 TI - Rapid resetting of baroreflexes in hypertensive dogs. AB - The hypothesis tested was that the rapid resetting of the arterial baroreflex control of arterial pressure in normotension could be demonstrated in experimental hypertension. After the development of experimental hypertension (using a bilateral renal wrap technique), rapid resetting of arterial pressure and heart rate (HR) was acutely assessed under pentobarbital sodium anesthesia in hypertensive and normotensive vagotomized dogs. The carotid sinus area was isolated and perfused at controlled carotid sinus pressures (CSPs). Baroreflex response [mean arterial pressure (MAP) and HR] curves were measured after three carotid sinus conditioning pressures (50, 125, and 200 mmHg) were applied. For the MAP response, the CSPo (CSP at point of maximum reflex gain) increased significantly to the same extent in both groups with increasing conditioning pressures (with 22.2 and 16.7% resetting in the normotensive group, and 20.3 and 14.2% resetting in the hypertensive group). We conclude that short-term adjustments to changes in prevailing pressure (rapid resetting) occur in the arterial pressure response in experimental hypertension to the same extent seen in normotension. PMID- 1590456 TI - Differences and similarities in albumin and red blood cell flows through cerebral microvessels. AB - The hypothesis that microvessels in brain parenchyma are continuously perfused by plasma but intermittently perfused by red blood cells (RBCs) was tested in awake Sprague-Dawley rats. The microvascular distribution volumes of radioiodinated serum albumin (RISA) and 51Cr- and 55Fe-labeled RBCs were measured for periods from 15 s to 30 min. Local cerebral blood flow (LCBF) was assessed by the iodoantipyrine technique. The RISA and RBC distribution volumes were constant in the 12 areas studied from 15 s onward. These data fit a model of continuous plasma flow with intermittent RBC flow (and thus support the hypothesis), but they are also consistent with other models, e.g., continuous flow of both plasma and RBCs through all perfused microvessels. In parallel with LCBF, microvascular blood volume varied greater than 10-fold among brain areas. Relative to arterial hematocrit, microvascular hematocrits were low, which indicates that the passage of RBCs through parenchymal microvessels is more rapid than that of RISA. This could be the result of both the Fahraeus effect and intermittent RBC flow. PMID- 1590457 TI - Internalized basic fibroblast growth factor translocates to nuclei of venular endothelial cells. AB - To begin to understand the molecular mechanisms by which basic fibroblast growth factor (bFGF) stimulates proliferation of coronary venular endothelial cells (CVEC), we have characterized the kinetic interactions of bFGF with various binding sites on CVEC and determined the kinetics of nuclear translocation of bFGF. We report that bFGF rapidly binds to its receptor and is immediately internalized at 37 degrees C with a half-time for receptor binding of 0.9 min. After internalization bFGF is processed by two kinetically and biochemically distinguishable pathways. Up to 40-50% of total internalized bFGF is translocated to the nuclei of serum-starved, quiescent cells at early time points (0-2 h). This proportion declines to less than or equal to 20% by 24 h. Cytoplasmic accumulation continued to increase for up to 24 h. Nuclear-bound 125I-labeled bFGF consisted primarily of the intact 18-kDa species with small amounts of a 16 kDa degradation fragment. Nuclear-bound 125I-labeled bFGF showed little evidence of degradation even after 24 h, whereas cytoplasmic 125I-labeled bFGF showed increased degradation to smaller fragments with time. Nuclear-binding of bFGF reached equilibrium by 8 h, just before initiation of DNA synthesis, which began 9-12 h after growth factor addition. These results suggest that nuclear-bound bFGF may function in triggering division (proliferation) of CVEC subsequent to binding of the growth factor to cell surface receptors. PMID- 1590458 TI - Prolonged adenine nucleotide resynthesis and reperfusion injury in postischemic skeletal muscle. AB - Skeletal muscle ischemia results in energy depletion and intracellular acidosis. Reperfusion is associated with impaired adenine nucleotide resynthesis, edema formation, and myocyte necrosis. The purpose of these studies was to define the time course of cellular injury and adenine nucleotide depletion and resynthesis in postischemic skeletal muscle during prolonged reperfusion in vivo. The isolated canine gracilis muscle model was used. After 5 h of ischemia, muscles were reperfused for either 1 or 48 h. Lactate and creatine phosphokinase (CPK) release during reperfusion was calculated from arteriovenous differences and blood flow. Adenine nucleotides, nucleosides, bases, and creatine phosphate were quantified by high-performance liquid chromatography, and muscle necrosis was assessed by nitroblue tetrazolium staining. Reperfusion resulted in a rapid release of lactate, which paralleled the increase in blood flow, and a delayed but prolonged release of CPK. Edema formation and muscle necrosis increased between 1 and 48 h of reperfusion (P less than 0.05). Recovery of energy stores during reperfusion was related to the extent of postischemic necrosis, which correlated with the extent of nucleotide dephosphorylation during ischemia (r = 0.88, P less than 0.001). These results suggest that both adenine nucleotide resynthesis and myocyte necrosis, which are protracted processes in reperfusing skeletal muscle, are related to the extent of nucleotide dephosphorylation during ischemia. PMID- 1590459 TI - Age-related changes in thoracic aorta of obese Zucker rats. AB - Studies were performed on the ontogeny of arterial blood pressure and functional properties of the thoracic aorta in lean (L) and obese (O) male Zucker rats at ages of 6-36 wk. Body weight was larger in the O than the L at all ages, with differences reaching values of 200-250 g at ages over 24 wk (at 33-36 wk: L = 510 +/- 9 and O = 730 +/- 15 g). Systolic blood pressure was lower in young O compared with L (6-15 wk) but increased with age at a rate seven times greater in O than in L. For ages of 33-36 wk, systolic pressure was significantly higher in O compared with L (O = 132 +/- 2 vs. L = 122 +/- 2 mmHg). Total serum cholesterol (at 36 wk: L = 278 +/- 31 and O = 354 +/- 12 mg/dl) and triglycerides (at 36 wk: L = 493 +/- 71 and O = 1,618 +/- 220 mg/dl), as well as glucose levels, increased with age in both groups and were significantly higher in O at all ages. Serum levels of thyroxine but not triiodothyronine were significantly lower in O at all ages. No differences were found in passive mechanics at any age. Values of maximum active stress with smooth muscle activation by 75 mM K+ plus 10 microM norepinephrine were significantly higher at 24 and 36 wk in O (at 36 wk: L = 573 +/- 42 and O = 821 +/- 89 x 10(3) dyn/m2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590460 TI - Endothelial L-arginine pathway and regional cerebral arterial reactivity to vasopressin. AB - Experiments were designed to characterize the mechanism of vasopressin action in small arteries of brain stem and cerebrum and to determine the role of L-arginine pathway in reactivity of these vessels to vasopressin. Secondary branches of canine basilar arteries (425 +/- 63 microns ID, n = 6) and middle cerebral arteries (466 +/- 30 microns ID, n = 6) were dissected and mounted on glass microcannulas in organ chambers. Changes in intraluminal diameter of the pressurized arteries were measured using a video dimension analyzer. Vasopressin caused endothelium-dependent relaxation in the brain stem arteries [-log half maximal effective concentration (EC50) = 9.2 +/- 0.4, n = 5] but not in the branches of middle cerebral arteries. In contrast, bradykinin caused identical endothelium-dependent relaxations in arteries of both regions (-log EC50 = 8.0 +/ 0.2, n = 5, and 7.7 +/- 0.1, n = 4 for brain stem and cerebrum, respectively). Relaxations to vasopressin (but not to bradykinin) were reduced in the presence of V1-vasopressinergic antagonist [1-(beta-mercapto-beta cyclopentamethylenepropionic acid),2-(O-methyl)tyrosine]arginine vasopressin [d(CH2)5-Tyr(Me)AVP;10(-7) M], pertussin toxin (100 ng/ml), and NG-monomethyl-L arginine (L-NMMA; 10(-4) M). The inhibitory effect of L-NMMA was prevented by L arginine (3 x 10(-4) M) but not D-arginine (3 x 10(-4) M). These studies suggest that vasopressin causes endothelium-dependent relaxation in canine brain stem arteries. The effect of the neuropeptide appears to be mediated by activation of endothelial V1-vasopressinergic receptors coupled to nitric oxide synthase. This signal transduction pathway is not functional in endothelial cells of branches of middle cerebral arteries. PMID- 1590461 TI - Vascular injury by endotoxin: changes in macromolecular transport parameters in rat aortas in vivo. AB - Vascular injury can lead to enhanced macromolecular transport into the arterial wall. We previously demonstrated that lipopolysaccharide (LPS) -induced injury to rat aorta in vivo caused increases in intimal and medial horseradish peroxidase (HRP) accumulation. In the present study, we quantitatively interpret these LPS induced changes in HRP transport parameters. The parameters of interest are the permeability (PL) of the luminal blood-tissue boundary (combination of endothelium and internal elastic lamina, IEL), the effective diffusivity (D), and the convective velocity (V) across the media. The parameter values that yield the best fit of the model to the data provide a basis for understanding the tissue changes. The time of peak transmural (medial) accumulation (24 h after LPS injection) correlated with increases in PL (peak, 12-48 h) and preceded the maximum increase in V (peak, 36 h). The monotonic increase in the intimal accumulation during the 5 days after the injury has a time course distinct from the transient increases in PL and from the changes in D, which implies that endothelial permeability has only limited influence on transport beyond the intima. These data implicate the IEL as a barrier to macromolecular transport in the normal aorta and demonstrate that the endothelium and IEL work in concert to determine intimal macromolecular accumulation. PMID- 1590462 TI - Lactic acidosis: effect of treatment on intracellular pH and energetics in living rat heart. AB - Systemic acidemia may impair cardiac contractility and predispose to arrhythmias. Moreover, bicarbonate treatment may further depress cardiac performance and increase mortality. Whether changes in myocardial intracellular pH or energy metabolism underlie this diminished performance has not been clarified in the in vivo setting. Thus we investigated the effect of lactic acidosis and two proposed treatments on myocardial energetics and intracellular pH in anesthetized living rats. A previously validated 31P-labeled nuclear magnetic resonance (31P-NMR) spectroscopic technique using saturating pulses was used to follow myocardial intracellular pH, phosphocreatine (PCr), ATP, and inorganic phosphate (Pi). After obtaining baseline values, we infused lactic acid to achieve a level greater than 5 mM. We then added an infusion of either bicarbonate (n = 7) or saline (n = 5). During lactic acid infusion, arterial pH declined (from 7.27 to 7.07, P less than 0.0001), but myocardial intracellular pH did not change (7.13 vs. 7.07, P not significant). The ratio of PCr to Pi, however, decreased with acidemia (from 3.13 to 2.24, P = 0.004), suggesting impaired energy metabolism. Compared with saline, bicarbonate infusion restored systemic pH (from 7.08 to 7.29), but myocardial pH was unaltered. In addition, PCr/Pi declined further following bicarbonate treatment (1.41 vs. 2.42, P = 0.08) but not following saline. Thus, despite reversal of systemic acidemia, bicarbonate treatment was associated with more severe impairment of energy metabolism than saline. This suggests a mechanism for previously reported adverse cardiac effects of bicarbonate treatment. PMID- 1590463 TI - Role of endothelium-derived relaxing factor in parasympathetic coronary vasodilation. AB - Vasodilation following the infusion of acetylcholine is due to the release of endothelium-derived relaxing factor (EDRF). However, the role of EDRF in neurogenic coronary vasodilation, when acetylcholine is released outside the vessel at the adventitial-medial junction, has not been established. The action of EDRF in parasympathetic coronary vasodilation was tested in the present study using a specific inhibitor of EDRF synthesis, nitro-L-arginine methyl ester (L NAME). Experiments were conducted on closed-chest, alpha-chloralose-anesthetized dogs with the heart paced at a constant rate. Phentolamine and propranolol were administered to block alpha- and beta-adrenergic receptors, and ibuprofen was given to inhibit prostaglandin synthesis. Intracoronary infusion of L-NAME decreased the coronary vasodilation in response to intracoronary acetylcholine or vagal stimulation. The coronary response to the endothelium-independent vasodilator nitroglycerin was unaffected by L-NAME. These data demonstrate that L NAME specifically inhibits coronary vasodilation caused by acetylcholine and vagal stimulation, indicating that parasympathetic coronary vasodilation is dependent on EDRF. PMID- 1590464 TI - Blood velocity distributions within intact canine arterial bifurcations. AB - As local variations in blood flow are implicated in atherogenesis at bifurcations, we measured in vivo blood velocities in different planes within exposed iliofemoral arterial bifurcations in 8 dogs using 20-MHz, 80-channel Doppler ultrasound velocimetry. Cardiac frequency was fixed at 2 Hz by pacing. Local geometry was characterized using 25-MHz, B-mode ultrasound images, photographs, and methacrylate casts. The bifurcations were asymmetrical and planar to within 5 degrees, the diameter ratios of the daughter vessels ranged from 1.47 to 2.00, and the angles between them ranged from 40 to 76 degrees. Measured velocities indicated that just upstream of the bifurcation mean peak Reynolds numbers ranged from 196 to 564 and Womersley (frequency) parameters ranged from 2.00 to 4.1. At the level of the bifurcation, secondary flows were insignificant in the normal plane but strong in the plane of the bifurcation. As a result, two-dimensional velocity fields, reconstructed by vector addition of velocities measured in the plane of the bifurcation, differed markedly from the one-dimensional profiles calculated assuming flow parallel to the vessel axis. In the two-dimensional velocity fields, forward flow was directed toward the flow divider and reversal occurred earliest near the outer wall. Wide spatial and temporal variations in the shear stress at the endothelium are implied by these detailed, in vivo measurements of the bifurcation velocity fields. PMID- 1590465 TI - Interactions of endothelins and EDRF in bovine native endothelial cells: selective effects of endothelin-3. AB - The tone of vascular smooth muscle is influenced by factors released from the endothelium, including endothelin (ET)-1 and endothelium-derived relaxing factor (EDRF). To better understand the interactions between these two mediators, we examined the release of both immunoreactive ET-1 (ir-ET-1) and EDRF from bovine aortic intact endothelium. Bovine aortas were opened longitudinally, washed, and clamped with the endothelium uppermost between two plates. The upper plate contained six openings forming identical and independent wells of endothelial cell monolayer. In experiments examining the release of EDRF, measured as accumulated NO2- and NO3- (NO chi -), we found that ET-3, calcium ionophore A23187 (A23187), acetylcholine (ACh), or ADP caused significant increase in NO chi- release, whereas ET-1 did not. These were significantly reduced in the presence of the EDRF/NO synthase inhibitor, NG-methyl-L-arginine (L-NMA). In a parallel series of experiments measuring EDRF release by stimulation of guanosine 3',5'-cyclic monophosphate (cGMP) accumulation in rat fetal lung (RFL)-6 cells, ET-3 but not ET-1 was also found to be active as a releaser of EDRF. A23187 caused an increase of ir-ET-1 release, whereas ACh, ADP, or the NO-containing compound sodium nitroprusside decreased the release of ir-ET-1. The depression in ir-ET-1 release in the presence of ACh or ADP was not seen when the endothelium was treated with L-NMA. When the cells were pretreated with 8-bromoguanosine 3',5'-cyclic monophosphate (8-bromo-cGMP), the release of ir-ET-1 in response to A23187 was significantly depressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590466 TI - EDTA influences reactivity of isolated aorta from hypercholesterolemic rabbits. AB - The effects of the trace metal chelator, ethylenediaminetetraacetic acid (EDTA), on endothelium-dependent reactivity of isolated aorta from normal and hypercholesterolemic rabbits were studied. Rings of abdominal aorta were mounted in organ chambers for measurement of isometric force and incubated in physiological salt solution with or without EDTA (26 microM). Aortic rings were obtained from rabbits fed a standard diet or a diet enriched with 0.5% cholesterol and 4% peanut oil for 10 wk. In rabbits fed the standard diet, endothelium-dependent relaxations to acetylcholine and A23187 were not significantly different in rings incubated in physiological salt solution with or without EDTA. In aortic rings from cholesterol-fed rabbits incubated in physiological salt solution with EDTA, the relaxations caused by either acetylcholine or A23187 were not significantly impaired compared with rings from rabbits fed a standard diet. Only in rings incubated in the absence of EDTA did hypercholesterolemia significantly inhibit endothelium-dependent relaxation compared with control rabbits. Relaxations to sodium nitroprusside were not different in rings incubated with or without EDTA in either group. Thus the effect of hypercholesterolemia on endothelium-dependent reactivity of rabbit aorta depends on the in vitro experimental conditions. This study emphasizes the importance of including a metal chelator in physiological solutions used in the in vitro study of blood vessels from hypercholesterolemic animals. PMID- 1590467 TI - Gravity and the circulation: "open" vs. "closed" systems. AB - The elementary principles of liquid dynamics are described by the equations of Bernoulli and Poiseuille. Bernoulli's equation deals with nonviscous liquids under steady streamline flow. Pressures in such flows are related to gravity and/or acceleration. Changes in elevation affect the gravitational potential energy of the liquid and the velocity of flow determines the kinetic energy. The sum of these three factors represented in the Bernoulli equation remains constant, but the variables are interconvertible. In contrast, the Poiseuille equation describes the pressures related to viscous resistance only, and the energy of flow is dissipated as heat. A combination of the two equations describes the flow in tubes more realistically than either equation alone. In "open" systems gravity hinders uphill flow and causes downhill flow, in which the liquid acts as a falling body. In contrast, in "closed" systems, like the circulation, gravity does not hinder uphill flow nor does it cause downhill flow, because gravity acts equally on the ascending and descending limbs of the circuit. Furthermore, in closed systems, the liquid cannot "fall" by gravity from higher levels of gravitational potential to lower levels of potential. Flow, up or down, must be induced by some source of energy against the resistance of the circuit. In the case of the circulation, the pumping action of the heart supplies the needed energy gradients. Flow in collapsible tubes, like veins, obeys the same basic laws of liquid dynamics except that transmural pressures near zero or below zero reduce markedly the cross-sectional area of the tube, which increases the viscous resistance to flow.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590468 TI - Renal nerves contribute to salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits. AB - The objective of this study was to investigate the role of the renal nerves in the pathogenesis of salt-induced hypertension in sinoaortic-denervated uninephrectomized rabbits. Twelve rabbits were divided into two groups. Sinoaortic-denervated uninephrectomized rabbits with intact renal nerves (sham group: n = 6) and without renal nerves (RDN group; n = 6). In both groups, 2 days of 154 meq/l NaCl loading was followed by 10 days of 1,700 meq/l NaCl loading. We administered 154 meq/l or 1,700 meq/l NaCl intravenously at every 8 h. Serial changes in mean arterial pressure (MAP) and heart rate (HR) were recorded using a microcomputer system. We chronologically measured hematocrit, serum osmolality, serum sodium, potassium, and chloride concentration, serum creatinine, plasma renin activity, plasma aldosterone, plasma norepinephrine, plasma arginine vasopressin, and plasma atrial natriuretic peptide. Urine volume and body weight were recorded every day, as were urinary concentrations of sodium, potassium, and chloride. The basal value of MAP in the sham group was significantly higher than that in the RDN group (on day -2, 111 +/- 1 mmHg for sham, 99 +/- 2 for RDN, P less than 0.001). Hypertonic saline loading induced an elevation of blood pressure in the sham group (126 +/- 2 mmHg on day 4, 127 +/- 2 on day 7, 124 +/- 4 on day 10). There were no significant changes in the response to salt loading in the RDN group. In the sham group, the retention of sodium was significant compared with that in the RDN group on day 5, and this difference was maintained until the end of the experiments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590469 TI - Autonomic cardiovascular responses to smoke exposure in conscious rats. AB - Autonomic cardiovascular responses and the change in renal sympathetic nerve activity (RSNA) in response to smoke exposure were investigated in unrestrained conscious rats. Smoke exposure caused a prominent increase in RSNA (to 557.3 +/- 221.9% of the control level) and plasma norepinephrine [from 0.18 +/- 0.08 (control) to 0.66 +/- 0.22 ng/ml (at peak response of smoke exposure)], a slight increase in arterial blood pressure (from 89.6 +/- 3.3 to 103.6 +/- 3.8 mmHg), and marked bradycardia (from 386.6 +/- 12.8 to 231.3 +/- 20.6 beats/min). Respiratory rate in conscious rats was initially increased (from 1.6 +/- 0.1 to 6.1 +/- 0.3 breaths/s) but was decreased (to 0.9 +/- 0.1 breaths/s) at the peak phase of the cardiovascular responses to smoke inhalation. Blood gases and pH reflected these changes in respiratory rate to some extent. Sinoaortic denervation did not attenuate the bradycardia (from 402 +/- 17.5 to 255.8 +/- 16.2 beats/min) or increase in RSNA (to 413.4 +/- 74.9%) that occurred during smoke inhalation. Atropine sulfate abolished the bradycardic response (from 440.4 +/- 13.8 to 485.4 +/- 8.6 beats/min). Initial tachypnea was also observed in both sinoaortic denervated rats and atropine-treated rats. Anesthesia, induced by pentobarbital sodium (30 mg/kg iv) or alpha-chloralose (65 mg/kg iv), abolished the bradycardia, the increase in RSNA, and the change in respiratory rate caused by smoke exposure. Ablation of the olfactory lobes also greatly attenuated the smoke-induced increase in RSNA (to 150.9 +/- 22.9%), bradycardia (from 372.9 +/- 19.6 to 376.3 +/- 24.1 beats/min), and the respiratory change.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590470 TI - Acute effects of captopril, an angiotensin-converting enzyme inhibitor, on the pregnant ewe and fetus. AB - After control measurements had been made, 15 chronically catheterized pregnant ewes (gestational age 123-141 days) were given 15 mg of captopril intravenously followed by an infusion of 6 mg/h. These doses blocked the pressor responses of both ewes and fetuses to 5 micrograms of angiotensin I. After captopril, maternal mean arterial pressure fell from 94 +/- 3.5 to 88 +/- 3.6 (SE) mmHg (P less than 0.0001) and pulse interval fell (P = 0.008). Maternal flow to the cotyledons fell from 766 +/- 118 to 525 +/- 77 ml/min (P = 0.002), as did flow to the remainder of the maternal placenta, i.e., the caruncles and their underlying myoendometrium (control flow 188 +/- 35 ml/min, flow 10-15 min after captopril 166 +/- 36.1 ml/min; P = 0.021). Flow to the rest of the myometrium did not change. Fetal arterial pressure fell from 46.9 +/- 1.6 to 44.1 +/- 1.6 mmHg (P less than 0.009), and fetal placental blood flow fell from 639.9 +/- 93.2 to 413.1 +/- 53.9 ml/min (P = 0.025). Flow to the fetal membranes declined also, from 53.2 +/- 6.5 to 35.6 +/- 3.3 ml/min (P less than 0.005). Maternal and fetal renal blood flows and fetal adrenal blood flows were unchanged. Fetal arterial PO2 was initially 19.5 +/- 0.8 mmHg; after captopril, it was 17.7 +/- 0.9 mmHg (P = 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590471 TI - Methylmercury transport across the blood-brain barrier by an amino acid carrier. AB - The mechanism by which methylmercury (MeHg) crosses the blood-brain barrier was examined in the rat. Previous studies demonstrated that intravenous injection of L-cysteine with MeHg accelerates MeHg uptake into brain. Since the complex of MeHg with L-cysteine is structurally similar to L-methionine, a substrate for the L (leucine-preferring) amino acid transport system, this carrier may be involved in MeHg uptake. To examine this hypothesis, the rapid carotid infusion technique was used in the anesthetized rat. The concentration dependence of 203Hg uptake into brain after injection of Me203Hg-L-cysteine complex was nonlinear, exhibiting characteristics of saturable transport (apparent Michaelis constant 0.39 mM, vmax 33 nmol.min-1.g-1). A slower, nonsaturable uptake was seen after MeHg-L-cysteine uptake was inhibited by methionine and the amino acid analogue 2 aminobicyclo[2.2.1]heptane-2-carboxylic acid (BCH), an L system substrate, but not by alpha-methylaminoisobutyric acid, an alanine-preferring system substrate. Furthermore, L-[14C]methionine transport was inhibited by MeHg-L-cysteine but not by MeHgCl. There was a significant amount of uptake of 203Hg when injected as Me203Hg-glutathione, and this was inhibited by L-methionine and BCH but not D methionine. S-ethylglutathione also inhibited 203Hg uptake after administration as Me203Hg-glutathione but had no effect on Me203Hg-L-cysteine uptake. These results suggest that MeHg may enter the brain as a cysteine complex via the L system and that plasma MeHg-glutathione serves as a source of MeHg-cysteine. PMID- 1590472 TI - Energetic cost of locomotion in the tammar wallaby. AB - Rates of oxygen consumption and blood lactate levels were measured in tammar wallabies (Macropus eugenii) trained to hop on a treadmill. In addition, the work required to overcome wind resistance during forward locomotion was measured in a wind tunnel. Up to approximately 2.0 m/s, rates of oxygen consumption increased linearly with speed and were not significantly different from rates of oxygen consumption for a quadruped of similar body mass. Between 2.0 and 9.4 m/s, rates of oxygen consumption were independent of hopping speed, and between 3.9 and 7.9 m/s, the range over which samples were obtained, blood lactate levels were low (0.83 +/- 0.13 mmol.min-1.kg-1) and did not increase with hopping speed. The work necessary to overcome drag increased exponentially with speed but increased the energy cost of locomotion by only 10% at the average speed attained by our fast hoppers. Thus, during hopping, the energy cost of locomotion is effectively independent of speed. At rates of travel observed in the field, the estimated energy cost of transport in large macropods is less than one-third the cost for a quadruped of equivalent body mass. The energetic savings associated with this unique form of locomotion may have been an important physiological adaptation, enabling large macropods to efficiently cover the distances necessary to forage in the semiarid landscapes of Australia. PMID- 1590473 TI - Regulation of calbindin mRNA and calbindin turnover in intestine and shell gland of the chicken. AB - A synthetic oligonucleotide was used as a probe for measurement of calbindin mRNA in the shell gland and intestine of chickens. The half time of calbindin mRNA in the duodenum and shell gland was estimated at 2 and 3.6 h and that of calbindin at 13.9 and 32.6 h, respectively. The formation rates of calbindin mRNA were 0.37 and 0.17 pmol.h-1.g-1 and the rate of calbindin formation was 0.099 and 0.031 microgram.pmol mRNA-1.h-1 in the duodenum and shell gland, respectively. In the shell gland, calbindin mRNA and calbindin appeared at the time of sexual maturation during calcification of the first egg shell. Calbindin mRNA fluctuated markedly during the daily egg cycle, in close temporal association with egg shell calcification. When Ca2+ deposition was eliminated by expulsion of the ovum, the rise in calbindin mRNA was prevented. An indirect suppression of Ca2+ deposition by administration of the carbonic anhydrase inhibitor acetazolamide also resulted in a decrease in calbindin mRNA. The results are consistent with a possible role of Ca2+ flux in the regulation of calbindin mRNA appearance in the shell gland of chickens. PMID- 1590474 TI - A method for identifying external control sites in metabolic systems. AB - A graphic method is presented for the identification of control sites in a metabolic system. This method is based on the matrix method for calculating net sensitivities developed by Crabtree and Newsholme (Biochem. J. 247: 113-120, 1987) and avoids the misidentification of control sites that can result from a simple inspection of a system. The method is easily adapted for analysis by computer and may be used for preliminary investigations of metabolic systems to identify potential control sites for further more quantitative investigations. PMID- 1590475 TI - Immunity to nerve growth factor and the effect on motor unit reinnervation in the rabbit. AB - The trophic effects of nerve growth factor (NGF) on sympathetic, peripheral afferent, and other neural crest-derived cells have been intensively investigated. More recently, NGF has been shown to have an influence on motoneurons. This study was undertaken to investigate whether NGF had any influence on the mechanical or histological properties of reinnervated motor units. Three groups of rabbits were used: normal rabbits, rabbits in which the nerve to medial gastrocnemius (MG) was cut and allowed to reinnervate for 56 days, and rabbits in which the MG nerve reinnervated in the presence of immunity to NGF. Immunity to NGF did not affect the ability of motor axons to reinnervate a muscle, nor were the contractile characteristics of the motor units altered. The size of horseradish peroxidase-labeled motoneurons was not influenced by immunization against NGF; however, the distribution of afferent neuron sizes was altered. Conduction velocity of motor axons proximal to the neuroma was significantly faster after immunization against NGF. Transection and subsequent reinnervation by a peripheral nerve normally causes an increase in myelin thickness proximal to the neuroma. However, immunization against NGF appeared to decrease the magnitude of myelin thickening. It was concluded that immunization against NGF affects motor axonal conduction velocity via an influence on the neural crest-derived Schwann cells. PMID- 1590476 TI - Relationship between vasopressin and renal concentrating ability in aging rats. AB - The relationship between arginine vasopressin (AVP) secretion and the age-related change in renal concentrating ability was studied in 10-, 20-, and 30-mo-old conscious rats. In control condition, urine osmolality (Uosmol) was 2,358 +/- 99, 1,919 +/- 87, and 1,135 +/- 173 mosmol/kgH2O (mean +/- SE) and the corresponding plasma AVP concentration 3.1 +/- 1.2, 2.8 +/- 0.7, and 3.3 +/- 0.7 pg/ml at 10, 20, and 30 mo. Urinary AVP excretion and AVP content in the hypothalamus were comparable in the 3 age groups, while the basal AVP pituitary content was significantly higher at 10 than at 20 or 30 mo. Three days of dehydration induced 1) a similar increase in plasma concentration and urinary excretion of AVP in the 3 groups, even though the maximal Uosmol reached by the oldest animals was significantly reduced (3,988 +/- 218, 3,652 +/- 273, and 2,826 +/- 197 mosmol/kgH2O at 10, 20, and 30 mo, respectively) and 2) a similar AVP depletion of the pituitary at 10, 20, and 30 mo and an increase of the AVP content in the hypothalamus at 10 mo but not at 20 and 30 mo. These results suggest that the decrease in renal concentrating ability reported in aging rats is not due to an inappropriate secretion of AVP along the hypothalamo-neurohypophysial axis but is rather related to an impaired responsiveness of the kidney to the antidiuretic hormone. PMID- 1590477 TI - Age-dependent changes in afferent renal nerve activity in genetically hypertensive rats. AB - Multiunit and single-unit recordings of afferent renal nerve activity (ARNA) were obtained in anesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats between 35 and 150 days of age. Intrapelvic backflow of urine at 20 mmHg excited ARNA at all ages in SHR (152 +/- 18% above control) and WKY rats (262 +/- 24%). In SHR, complete renal ischemia was more excitatory in rats older than 120 days (1,233 +/- 103%, n = 8) than in younger SHR (317 +/- 28%, n = 42). Single-unit recordings showed that this was related to the appearance of R1 chemoreceptors in older SHR and coincided with a decline in the proportion of R2 chemoreceptors in the renal nerves. Other chemoreceptive responses were identified in single units that did not show complete R1 or R2 characteristics, some of which showed responses consistent with a transformation process from R2 to R1 receptor type. R1 chemoreceptors were not present in WKY rats studied up to 150 days of age and, unlike SHR, the proportion of R2 chemoreceptors did not decline with age. Accordingly, complete renal ischemia in WKY rats caused a comparable excitation in multiunit ARNA at all ages (285 +/- 33%, n = 43). Oral enalapril from weaning to 100 days of age prevented hypertension in SHR but did not impair the responsiveness of ARNA to any stimulus. In WKY rats, enalapril treatment for the same period resulted in exaggerated ARNA response to renal ischemia (1,250 +/- 377% above control).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590478 TI - Intermittent exercise alters endurance in an eight-legged ectotherm. AB - Most animals move intermittently, yet many proposed performance limitations of terrestrial locomotion are based on steady-state measurements and assumptions. We examined the effect of work-rest transitions by exercising the ghost crab, Ocypode quadrata (28.1 +/- 8.1 g), intermittently on a treadmill at 0.30 m/s, a supramaximal speed [i.e., greater than the speed that elicits the maximal rate of oxygen consumption (VO2)]. Duration of the exercise and pause periods, ratio of exercise to pause, and speed during the exercise period were varied to determine the effect on performance. Crabs fatigued after 7.5 min of continuous running, a distance capacity (i.e., total distance traveled before fatigue) of 135 m. When the task was done intermittently with 2-min exercise and 2-min pause periods, the crabs fatigued after 87 min (a total distance of 787 m), representing an 5.8-fold increase in distance capacity compared with continuous exercise at the same absolute speed (0.30 m/s) and a 2.2-fold increase in distance capacity compared with continuous exercise at the same average speed (0.15 m/s). Pause periods less than 30 s did not result in greater distance capacity compared with continuous exercise at the same average speed. Longer (3-5 min) and shorter exercise periods (less than or equal to 30 s) decreased distance capacity. Leg muscle lactate increased 10-fold to 15 mumol/g leg during intermittent exercise. However, significant amounts of lactate were cleared from the leg during the brief pause periods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590479 TI - Decreased cardiorespiratory effects of neuropeptide Y in the nucleus tractus solitarius in diabetes. AB - It has been observed that diabetes results in increased neuropeptide Y (NPY) in various brain regions, especially the paraventricular nucleus, which projects to the nucleus of the solitary tract (NTS). Because previous studies indicated a pathophysiological relationship between diabetes and NPY, we investigated the effect of diabetes on the sensitivity of NTS-mediated responses to NPY administration. Rats were made diabetic using streptozocin (55 mg/kg iv) and maintained for 48 to 50 days. Normal and streptozocin-diabetic rats were anesthetized with urethan and alpha-chloralose, instrumented for cardiovascular and respiratory monitoring, and positioned in a stereotaxic apparatus. The brain stem was exposed surgically. NPY (0.15 nmol/kg) was microinjected into the NTS and the cardiovascular and respiratory parameters were monitored for 60 min. Diabetes increased systolic (SAP), diastolic (DAP), and mean (Pa) blood pressure but not pulse pressure (PP) and heart rate (HR). Respiratory parameters were not altered. NPY significantly decreased SAP, DAP, Pa, PP, HR, respiratory rate, and minute volume in normal animals. In diabetic animals, NPY also decreased SAP, DAP, and Pa but pronouncedly increased PP. Although NPY decreased the SAP and Pa in diabetic animals, the response was attenuated compared with normal animals. The respiratory parameters and HR of diabetic animals, unlike normal animals, did not respond to NPY administration. We conclude that chronic diabetes results in a decreased sensitivity to NTS-mediated responses and that the hyporesponsiveness of the NTS to NPY modulation may be important in the tendency toward elevated blood pressure and hypertension in diabetes. PMID- 1590480 TI - Identification of carotid vascular receptors that control adrenal catecholamine secretion in dogs. AB - The role of carotid sinus and thyrocarotid mechanoreceptors in the reflex control of adrenal medullary function was assessed in anesthetized dogs with adrenal vein catheters. Dogs underwent carotid sinus, thyrocarotid junction, combined carotid sinus and thyrocarotid junction, or sham denervation. On the day after surgery, catecholamine secretion was measured after carotid occlusion proximal to the thyrocarotid junction, cervical vagotomy, and repeat carotid occlusion, each separated by 90 min. After combined carotid denervation, baseline norepinephrine secretion was increased, resulting in a decreased epinephrine-to-norepinephrine ratio. Carotid occlusion before vagotomy did not change the secretion of catecholamines or the epinephrine-to-norepinephrine ratio. After sham carotid denervation, acute vagotomy did not affect catecholamine secretion. However, after denervation of the carotid sinus or thyrocarotid junction, vagotomy resulted in small increases in catecholamine secretion without changing the epinephrine-to-norepinephrine ratio; the magnitude of the response was augmented after combined denervation. At 90 min after vagotomy in dogs with intact carotid baroreceptors, carotid occlusion increased adrenal secretion of catecholamines and decreased the epinephrine-to-norepinephrine ratio. After denervation of carotid sinus or thyrocarotid junction receptors, carotid occlusion increased secretion of catecholamines without changing the epinephrine-to-norepinephrine ratio; the response was abolished by combined denervation. These results show that both carotid sinus and thyrocarotid receptors contribute to the adrenomedullary response to carotid occlusion and to acute vagotomy. Also, reduction in the activity of carotid sinus and thyrocarotid junction receptors chronically (by denervation) or acutely (by carotid occlusion) results in preferential secretion of norepinephrine over epinephrine. PMID- 1590481 TI - Role of lung inflation in control of air breath duration in African lungfish (Protopterus annectens). AB - Studies were conducted in the African lungfish (Protopterus annectens) to investigate the role of lung inflation on control of the duration of the lung breath. The studies were done in decerebrate spinalectomized animals. Two types of tests were performed: 1) a no-inflation test (airway occluded) in which the lungs were not inflated during an air breath, and 2) an inflation test in which the lungs were inflated at the onset of the lung breath to different levels of intrapulmonary pressure (2.5, 5.0, 7.5, and 10.0 cmH2O). Lung inflation shortened the duration of the lung breath. The relationship between intrapulmonary pressure and breath duration was curvilinear and similar to the relationship between tidal volume and inspiratory duration in mammals. Likewise, the relationship could be described by a hyperbola with a linear relationship between intrapulmonary pressure and the inverse of breath duration. This relationship was essentially not affected by changing the composition of the gas used to inflate the lungs: air, oxygen, or nitrogen. Vagotomy, however, largely abolished the effect of lung inflation on breath duration. Because there is such similarity between these results and effect of lung inflation on control of inspiratory time in mammals, it is postulated that neural circuits for control of respiratory timing were already developed and similar in the lungfish. Because the muscles used in the lungfish to ventilate the lung are totally different (buccal force pump) from those in mammals, the neural circuits for timing control and those for shaping the pattern of motor output appear to be separate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590482 TI - Seasonal variation in the human circadian rhythm: dissociation between sleep and temperature rhythm. AB - The circadian rhythms of sleep-wakefulness, rectal temperature, and plasma melatonin were measured in 10 healthy male subjects for five consecutive seasons. To minimize direct effects of seasonally changing environmental factors, the subjects stayed in a living facility for 4 days in each season, where ambient temperature, humidity, and social contacts were controlled, while the light intensity of the living room was substantially influenced by natural daylight. Seasonal variations were found in the timing of sleep, the mean body temperature, the phases of circadian temperature and melatonin rhythms, and the phase relation between sleep and the rectal temperature rhythm. The subjects went to bed earliest in summer, intermediate in spring and autumn, and latest in winter. A similar but more pronounced seasonality was observed in the wake-up time, which was earlier in summer than in winter. The acrophases of the rectal temperature and plasma melatonin rhythms, which were calculated by fitting a cosine curve, were located in an earlier time of day in summer than in winter. The phase-angle difference of the rectal temperature rhythm to sleep varied seasonally and was more positive in summer than in winter. These findings indicate that not only the external (to the local time) but also the internal (between circadian rhythms) phase relations of the human circadian rhythms depend on season. PMID- 1590483 TI - Effect of increased neck vein pressure on intestinal lymphatic pressure in awake sheep. AB - Lymphatic vessels from the intestines drain into the thoracic duct, and the thoracic duct empties into veins in the neck. Thus increases in neck vein pressure (PNV) might slow intestinal lymph flow, provided the increased pressure is reflected upstream through the lymphatic vessels. To test the effect of increases in PNV on lymphatic pressure, we cannulated intestinal lymphatics in the direction of flow in six sheep. After the sheep recovered from surgery, we measured the pressure in the lymphatics (Px) as we increased PNV in steps. Px increased only slightly (but significantly) from 7.4 +/- 2.0 to 11.4 +/- 5.2 (SD) cmH2O when we increased PNV from baseline (0.8 +/- 2.4 cmH2O) to 37.4 +/- 4.1 cmH2O. However, when we simulated an increased lymph flow by infusing Ringer solution into the lymphatics at 1,000 microliters/min, Px increased to 24.6 +/- 7.0 cmH2O at PNV equal to 37.1 +/- 5.3 cmH2O. These results indicate that, at normal lymph flow rates, increases in neck vein pressure cause only small increases in intestinal lymphatic pressure. On the other hand, when lymph flow is elevated, increases in neck vein pressure may substantially increase lymphatic pressure and thus slow intestinal lymph flow. PMID- 1590484 TI - Stretch-mediated visceral smooth muscle growth in vitro. AB - An in vitro model of smooth muscle stretch was developed to study mechanical stimulus as a possible mediator of visceral smooth muscle growth and differences in the growth response of smooth muscle from young and old animals. De novo DNA synthesis as measured by the aphidicolin-sensitive specific activity of DNA was used as an index of cell growth. Compared with old tissue, the rate of aphidicolin-sensitive DNA synthesis in smooth muscle from young animals was 3-5 and 1.5-2 times greater in bladder and taenia coli, respectively. Stretch of bladder muscle and taenia coli strips from young animals for 6 h increased the aphidicolin-sensitive specific activity of DNA 3-fold (P less than 0.01) and 1.5 fold (P less than 0.01), respectively. Tissue from old animals, however, under the same conditions increased the rate of aphidicolin-resistant DNA synthesis, possibly implying DNA repair. Autoradiography showed only labeled myocyte nuclei. These results indicate that homeostatic mechanisms modulating myocyte growth in visceral smooth muscle can respond to mechanical stimulus in the absence of other trophic factors. PMID- 1590485 TI - Maturational differences in acetazolamide-altered pH and HCO3 of choroid plexus, cerebrospinal fluid, and brain. AB - The carbonic anhydrase inhibitor acetazolamide is useful for analyzing ion transport, pH regulation, and fluid formation in developing central nervous system. We used the 14C-labeled dimethadione technique to measure alterations in steady-state pH, and to estimate the HCO3 concentration [HCO3], in choroid plexus (CP), cerebrospinal fluid (CSF), and cerebral cortex of 1- and 3-wk-old Sprague Dawley rats treated with acetazolamide or probenecid. These drugs can suppress transport of HCO3 and other anions in some cells, consequently altering intracellular pH. In 1-wk-old infant rats whose CSF secretory process is incompletely developed, 1 h of acetazolamide treatment did not significantly change CP intracellular pH or [HCO3]. However, in 3-wk-old rats, in which the ability of CP to secrete ions and fluids is almost fully developed, acetazolamide caused marked increases in CP cell intracellular pH and [HCO3]. In contrast, acetazolamide-induced alkalinization was not observed in CSF or cerebral cortex of the 1- and 3-wk-old animals. The other test agent, probenecid (an inhibitor of anion transport but not of carbonic anhydrase), did not alter the pH of any region at any age investigated. Overall, the results are interpreted in light of developmental changes in carbonic anhydrase and previous findings from kinetic analyses of ion-translocating systems in CP. Acetazolamide may interfere with a CP apical membrane HCO3 extrusion mechanism not fully operational in infant rats. PMID- 1590486 TI - Fluid retention after oral loading with water or saline in camels. AB - When dehydrated camels are offered water they drink volumes of water exceeding their body water loss during the water deprivation period. The excess water is excreted during 2-4 days. To investigate the ability to retain fluid in the body, normohydrated camels were loaded with water or isotonic saline (0.1 l/kg body wt) by esophageal tube. After water loading plasma osmolality decreased and a water diuresis was seen, but it took 3 days until the body weight returned to prehydration level. Plasma aldosterone concentration (PAC) increased, but plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP) concentration did not change. After the saline loading plasma osmolality increased and total plasma proteins and hematocrit decreased. Renal Na excretion increased 4 h after the saline load, but the magnitude of the natriuresis was small, and the camels had not regained their body weight 6 days after the load. PAC and PRA decreased after saline loading, while plasma ANP concentration did not change. These data show that camels are able to retain excess water within the body and to tolerate blood hyposmolality for a relatively long time. With saline the retention of fluid lasts even longer despite an attenuation of PAC. PMID- 1590487 TI - Tissue specificity of SNS response to exercise in mice exposed to low temperatures. AB - The present study was carried out to investigate the tissue specificity of the sympathetic nervous system (SNS) response to acute exercise in adult mice exposed to four ambient temperatures. SNS activity estimates in heart, pancreas, and brown adipose tissue (BAT) were obtained from the measurement of the dopamine (DA) tissue contents 1 h after the inhibition of the DA-beta-hydroxylase with 1 cyclohexyl-2-mercaptoimidazole (CHMI). DA was measured by electrochemical detection after the separation of the monoamine using high-performance liquid chromatography. In both heart and pancreas, temperature and activity influenced DA tissue contents after the CHMI injection. In these tissues, and regardless of whether mice were resting or exercising, the DA contents gradually increased while the ambient temperature was dropped from a thermoneutral temperature of 32 to 5 degrees C. In BAT, however, there was a significant interaction between temperature and activity on the tissue DA content; in contrast to what was observed in resting animals, DA did not uniformly augment in exercising mice when the temperature was decreased from 32 to 5 degrees C. In summary, the present results show that exercise can attenuate the stimulating effect of cold on SNS activity in BAT. This effect is seemingly specific to BAT because, in mice exposed to low ambient temperatures, SNS activity in both heart and pancreas is not lower in exercising than in resting animals. PMID- 1590488 TI - Renal blood flow varies during normal activity in conscious unrestrained rats. AB - The extent to which renal blood flow (RBF) varied during normal daily activity and its dependence on renal nerve activity were studied in unrestrained rats. RBF (measured with a pulsed Doppler flow probe) and behavior pattern (observed with a video camera) were recorded during both phases of the light-dark cycle (n = 11). RBF was highest (100%) when the rat was fully relaxed and apparently asleep (9% time) but was significantly lower (P less than 0.01) during the remainder of the time. When quiescent but not fully relaxed, RBF was 89.7 +/- 0.3% of the maximum; when alert and completely still, it was 74.1 +/- 0.8%; and when grooming, it was 63.7 +/- 0.9%. Mean daily RBF was 80% of maximum flow. During saline infusion into cuffs around the renal arteries, RBF was reduced to 38.4 +/- 0.7% of maximum flow by gentle handling. When the infusion was changed to Xylocaine (5%), which blocked transmission in the renal nerve, similar treatment reduced RBF to 80.2 +/ 0.7% with ipsilateral and to 94.7 +/- 0.7% with bilateral infusions. We conclude that RBF varies considerably in unrestrained animals under normal conditions and that the variations largely result from changes in renal nerve activity. PMID- 1590489 TI - Micropuncture study of avian kidney: effect of prolactin. AB - Renal function was studied in anesthetized European starlings (Sturnis vulgaris) by micropuncture and clearance techniques. A previous study had shown some changes in the renal function of birds in molt. Endogenous prolactin levels have been shown to be elevated at this time. In the present study, renal function was studied during the infusion of an isotonic sodium chloride solution and then when ovine prolactin was added to the infusion. Ovine prolactin resulted in an elevation of plasma urate concentration but had no significant effects on other plasma parameters or on the concentration of the various ions in tubular fluid samples. Urine flow rate was significantly higher during prolactin infusion, although whole animal glomerular filtration rate, single nephron glomerular filtration rate, and the percentage fluid reabsorption in the proximal tubule (up to the point of micropuncture) were unaltered. The whole animal fractional excretions of sodium and chloride were significantly higher, those of magnesium and potassium were significantly lower, and the fractional excretion of phosphate tended to be lower during prolactin infusion. At the level of the proximal tubules of the reptilian-type nephrons, prolactin infusion caused a slight reduction in the net reabsorption of sodium and chloride. Therefore the main effects of prolactin on renal function are occurring in the distal nephron of the reptilian-type nephrons or in the mammalian-type nephrons. It appears that prolactin may affect renal function in avian species and that these actions may be modulated by a range of factors as has been demonstrated in mammals. PMID- 1590490 TI - Philippe Pinel's "Memoir on Madness" of December 11, 1794: a fundamental text of modern psychiatry. AB - Philippe Pinel's "Memoir on Madness" can now be precisely dated. It was read to the Society for Natural History in Paris on Dec. 11, 1794, soon after the fall of the Jacobin dictatorship. It is thus a political document, an appeal to the Revolutionary government to build asylums where the mentally ill could be decently treated. It is translated here for the first time. Philippe Pinel (1745 1826) served as "physician of the infirmaries" at Bicetre, the public hospice for men near Paris, from 1793 to 1795. In the "Memoir on Madness" he explains his "psychologic treatment," the principles of the humane method that made him the founder of psychiatry in France. Pinel states that mental illness is often curable. To arrive at a diagnosis, the physician must carefully observe a patient's behavior, interview him, listen carefully, and take notes. He must understand the natural history of the disease and the precipitating event and write an accurate case history. Diagnosis and prognosis can then be made. Periodic patterns of mental illness can be helpful for therapy. Usually only one faculty is affected. Patients with delusions may be malicious or murderous. They may have to be restrained; it was Pinel's assistant, Jean Baptiste Pussin, who removed the chains from the insane men at Bicetre Hospice in 1797 and replaced them with strait-jackets. Pinel followed suit at the Salpetriere, the public hospice for women, 3 years later. Pinel here states that one must "dominate agitated madmen while respecting human rights." PMID- 1590491 TI - Psychotic (delusional) major depression: should it be included as a distinct syndrome in DSM-IV? AB - To review data supporting or not supporting the designation of unipolar psychotic major depression as a distinct syndrome in DSM-IV, the authors used computerized literature searches to identify reports of studies that have directly compared the characteristics, biology, familial transmission, course/outcome, and response to treatment of psychotic and nonpsychotic major depression. The review showed that statistically significant differences between the two types of depression have been found on each of these dimensions. There are greater guilt feelings and psychomotor disturbance, among other features, in psychotic depression. Studies have found significant differences between patients with psychotic and nonpsychotic depression in glucocorticoid activity, dopamine beta-hydroxylase activity, levels of dopamine and serotonin metabolites, sleep measures, and ventricle-to-brain ratios. Family studies show higher rates of bipolar disorder in first-degree relatives of probands with psychotic major depression than of probands with nonpsychotic major depression. Greater morbidity and residual impairment have also been reported in patients with psychotic major depression, and they respond more poorly to placebo and to tricyclic antidepressants. Differences between patients with psychotic and nonpsychotic major depression on many of these measures were not due to differences in severity or endogenicity. Since the data indicate that psychotic and nonpsychotic major depression can be separated, the frequency with which the diagnosis of psychotic major depression is missed and its unique course and response to treatment point to the practical importance of a separate diagnosis for this disorder. However, further studies are needed to resolve important methodological issues and to develop an optimal set of operational criteria. PMID- 1590492 TI - Predicting substance use in late adolescence: results from the Ontario Child Health Study follow-up. AB - OBJECTIVE: The purpose of this study was to evaluate the relationship between use of tobacco, alcohol, marijuana, and hard drugs (substance use) and psychiatric disorder in early adolescence and substance use in late adolescence. METHOD: Adolescents included in the study were identified by means of a household sampling frame and participated in the Ontario Child Health Study in 1983 and the follow-up in 1987. There were 726 12-16-year-olds (369 boys and 357 girls) in 1983 who had complete information in 1987. Data on substance use were collected from adolescents by using a structured, self-administered questionnaire. Data on psychiatric disorder were collected in 1983 from both adolescents and their parents by using problem checklists to assess conduct disorder, attention deficit disorder, and emotional disorder. RESULTS: Prior substance use in 1983 was associated strongly with subsequent use in 1987. Among the psychiatric disorders assessed in 1983, only conduct disorder made an independent contribution to predicting use of marijuana (relative odds = 3.46) and other hard drugs (relative odds = 6.82) in 1987, after prior use of these substances and coexisting attention deficit and emotional disorders were controlled. Corresponding estimates of attributable risk (the expected contribution of exposure to conduct disorder to the development of substance use) were 5.7% and 11.1%, respectively. CONCLUSIONS: Although a statistically significant relationship existed between conduct disorder in early adolescence and use of marijuana and hard drugs in late adolescence, the potential is limited for preventing substance use in the general population by treating conduct disorder early on. PMID- 1590493 TI - A note on racial bias in the admission of children and adolescents to state mental health facilities versus correctional facilities in New York. AB - OBJECTIVE: In response to several studies suggesting that there is racial bias in the admission of proportionately more white children and adolescents to the child and adolescent mental health system than to the juvenile justice system, the authors tested whether white children and adolescents would be overrepresented compared with black children and adolescents in mental health facilities and underrepresented compared with black children and adolescents in juvenile correctional facilities when ethnic distribution in the general population was controlled. METHOD: Ethnicity, age, and sex of all white, black, and Hispanic 10 18-year-olds admitted in a 1-year period to facilities of the Office of Mental Health and facilities of the correctional system (the Division for Youth) of New York State were converted into rates per 100,000 population by using U.S. census data for the state. Admission rates per 100,000 population for ethnicity, age, sex, and source of referral were then compared in the two types of facilities. RESULTS: There were no meaningful differences in population-corrected admission rates among black, white, and Hispanic children and adolescents in the state mental health system. In contrast, there was a vast preponderance of black children and adolescents admitted to the state juvenile correctional system. The systems have different points of entry: 100% of the juvenile justice admissions versus 17% of the mental health admissions were referred by the courts. CONCLUSIONS: Analysis of demographic variables failed to support an allegation of racial bias in admission to the child and adolescent public mental health system in New York State. PMID- 1590494 TI - A crossover study of focused cognitive therapy for panic disorder. AB - OBJECTIVE: This study sought to determine the short- and long-term effects of focused cognitive therapy for panic disorder. METHOD: Thirty-three psychiatric outpatients with the DSM-III diagnosis of panic disorder were randomly assigned to either 12 weeks of individual, focused cognitive therapy or 8 weeks of brief supportive psychotherapy based on principles of client-centered therapy. The patients who received supportive psychotherapy were subsequently given the opportunity to cross over to cognitive therapy for 12 weeks. Patients were rated for panic and depression before therapy, after 4 and 8 weeks of therapy, and at 6 month and 1-year follow-up. RESULTS: Clinician ratings and self-ratings of panic frequency and intensity indicated that the focused cognitive therapy group achieved significantly greater reductions in panic symptoms and general anxiety after 8 weeks of treatment than did the group that received brief supportive psychotherapy. At 8 weeks, 71% of the cognitive therapy group were panic free, compared to 25% of the psychotherapy group. Moreover, 94% of the psychotherapy patients elected to cross over to 12 weeks of cognitive therapy. At 1-year follow up, 87% of the group that received cognitive therapy only and 79% of the group that crossed over into cognitive therapy remained free of panic attacks. CONCLUSIONS: Focused cognitive therapy offers a promising nonpharmacological alternative for the treatment of panic disorder. PMID- 1590495 TI - Qualitative assessment of brain morphology in acute and chronic schizophrenia. AB - OBJECTIVE: Neuroimaging studies of brain morphology in schizophrenia have used predominantly morphometric techniques to assess brain scans. However, as currently implemented, such methods are not particularly helpful in the routine assessment of individual patients. The purpose of this study was to evaluate brain morphology seen with magnetic resonance imaging (MRI) by qualitative assessment, the most frequently used method in clinical practice for evaluating brain scans. METHOD: First-episode (N = 62) and chronic, multi-episode (N = 24) schizophrenic patients and healthy comparison subjects (N = 42) underwent MRI of the whole head in a sequence that provided 63 contiguous brain slice images. Each subject received a rating of normal, questionably abnormal, or definitely abnormal for four brain regions (lateral ventricles, third ventricle, medial temporal lobe structures, and frontal/parietal cortex) and a global rating. RESULTS: The schizophrenic patients had significantly higher global rates of abnormal morphology (first-episode group, 31%; chronic group, 42%) than the normal subjects (5%). The highest regional rates of abnormalities were seen in the lateral ventricles and the lowest in the frontal/parietal cortex. Although the chronic patients had generally higher abnormal rates than the first-episode patients, these differences were not statistically significant. The qualitative ratings of brain morphology were significantly correlated with quantitative assessments performed in separate studies. CONCLUSIONS: Despite its limits in sensitivity (and until quantitative morphometric techniques are made practical and more widely available), qualitative evaluation of MRI scans can be a useful technique in research and clinical evaluation of patients with schizophrenia. PMID- 1590496 TI - Pattern of recurrence of illness after recovery from an episode of major depression: a prospective study. AB - OBJECTIVE: This study assessed prospectively the pattern of recurrence of illness after recovery from an episode of major depression. METHOD: Seventy-two patients who had recovered from an episode of primary, nonbipolar, nonpsychotic major depression were evaluated bimonthly with the Comprehensive Psychopathological Rating Scale for a period ranging from 20 to 108 months (median = 66 months). New ("prospective") episodes were ascertained with a structured diagnostic interview. The probabilities of remaining well after the index episode and after the first prospective episode were assessed by the life-table method. The severity and duration of prospective episodes and the index episode were compared by linear regression analysis. RESULTS: The probability of remaining well after recovery from the index episode was 76% at 6 months, 63% at 1 year, and 25% at 5 years. The risk of recurrence was lower among patients receiving prophylactic treatment with antidepressants and/or lithium and among those with histories of fewer than three previous episodes. The probability of remaining well was significantly lower 2 years after the first prospective episode than 2 years after the index episode. A pattern of increasing severity from the index episode to the first, second, and third prospective episodes was observed and was not affected by treatment. CONCLUSIONS: Major depression has a high rate of recurrence, even when bipolar and psychotic cases are excluded. The highest rate is observed during the first months after recovery from an episode. Prophylactic drug treatment reduces the risk of recurrence but apparently does not affect the trend toward increasing severity of subsequent episodes. PMID- 1590497 TI - Lithium, benzodiazepines, and sexual function in bipolar patients. AB - OBJECTIVE: Lithium and benzodiazepines are widely used in the treatment of bipolar patients. Yet studies of the effect of these drugs on sexual function are scarce. This study surveyed sexual function in bipolar patients treated with lithium, either alone or in combination with other drugs. METHOD: Sexual function was assessed by self-rating scale in 104 outpatients (45 men and 59 women) with a DSM-III diagnosis of bipolar disorder who were attending an affective disorders clinic. All patients were under treatment with lithium, either alone (35%) or in combination with benzodiazepines (49%), tricyclic antidepressants (17%), neuroleptics (17%), tryptophan (10%), or carbamazepine (1%). The patients were in a stable and euthyroid state at the time of the assessment. Serum lithium and plasma prolactin concentrations were measured at the same time. RESULTS: Multiple regression analysis revealed an association between concomitant benzodiazepine administration and sexual dysfunction scores. Difficulties in sexual functioning were significantly more common in patients treated with a combination of lithium and benzodiazepines (49%) than in those treated with either lithium alone (14%) or lithium in combination with other drugs (17%). No relationship was found between serum lithium or plasma prolactin levels and sexual dysfunction scores. CONCLUSIONS: Lithium, when given alone, did not appear to have a major effect on sexual function, whereas its combination with benzodiazepines was associated with sexual dysfunction in about half of the patients. More attention should be given to drug-induced sexual dysfunction, since its presence can have important consequences for clinical management and compliance. PMID- 1590498 TI - Learned helplessness and urinary MHPG levels in unipolar depression. AB - OBJECTIVE: Studies of the learned helplessness paradigm in laboratory animals show increased central noradrenergic activity following exposure to uncontrollable stressors. In clinical studies, depressed patients as a group report higher perceptions of helplessness and powerlessness. The authors examined the relationship between perceptions of powerlessness and noradrenergic activity in depressed patients. METHOD: Twenty drug-free patients (12 women and 8 men) meeting DSM-III criteria for major depressive disorder were given the Kobasa Hardiness Questionnaire, which contains subscales measuring feelings of powerlessness, security, and alientation. Concurrently, 24-hour urine samples were collected for measurement of urinary MHPG. RESULTS: Significant correlations were found between MHPG levels and total hardiness scores as well as between MHPG levels and total powerlessness scores but not between MHPG levels and total security or total alientation scores. CONCLUSIONS: These results suggest that depressed patients with high urinary output of MHPG are more likely to show the cognitive features of learned helplessness. PMID- 1590499 TI - Crack/cocaine abusers in the general hospital: assessment and initiation of care. AB - OBJECTIVE: Cocaine, either smoked (as "crack") or taken intranasally, is now a common cause of psychiatric illness. This study was designed to assess the impact of cocaine abuse on a general psychiatric service and an obstetrics service in an urban general hospital and to evaluate a program for engaging affected patients in addiction treatment. METHOD: The charts of 300 general psychiatric patients (not admitted for addiction treatment) and 60 cocaine-abusing prenatal or postpartum patients were reviewed. A treatment referral program based on professionally directed peer leadership was established for patients with cocaine abuse. Results of evaluation and referral of 100 other cocaine-abusing psychiatric patients and the 60 prenatal or postpartum patients were then determined. RESULTS: Fully 64% (N = 191) of the 300 psychiatric patients were diagnosed as substance abusers; 38% (N = 113) of them abused cocaine. Almost one third of these cocaine abusers had no axis I diagnosis other than substance abuse/dependence, and the majority were homeless. Urine samples were positive for cocaine in a majority of the obstetric patients studied. A majority of the psychiatric patients who were referred through the peer-led program enrolled in outpatient cocaine treatment--three times as many as in the chart review group. Most of the obstetric patients suitable for referral enrolled for treatment as well. CONCLUSIONS: Cocaine abuse may be responsible for a large portion of psychiatric admissions in urban public general hospitals. Cocaine abusers in psychiatric and obstetrics services are apparently responsive to a peer-oriented mode of referral into treatment. PMID- 1590500 TI - Homeless mentally ill or mentally ill homeless? AB - Mainstream psychiatry conceptualizes people who are homeless and mentally ill as distinct from other homeless persons because it is thought that their status stems from their mental disorder and the poor implementation of deinstitutionalization. The authors believe this dichotomy is illusory. They present data indicating that recent socioeconomic and political shifts contributed greatly to homelessness among all groups, regardless of mental illness; that those with and without mental illness have similar biographical and demographic profiles; that high levels of mental distress are common to all homeless persons; and that few mentally ill homeless persons require involuntary hospitalization. This perspective suggests novel responses that de-emphasize clinical solutions and focus on empowerment, consumerism, entitlement, community level interventions, and closer alliances with other advocates for the homeless. PMID- 1590501 TI - Are panic attacks traumatic stressors? AB - Like typical stressors that produce posttraumatic stress disorder (PTSD), panic attacks are sudden, unpredictable, and often perceived as life-threatening. Structured interviews with 30 subjects with panic disorder revealed that five (17%) and two (7%) met lifetime and current DSM-III-R PTSD criteria, respectively, following their most terrifying panic attack. PTSD produced by panic is less severe than PTSD produced by either rape or combat. PMID- 1590502 TI - Onset of panic disorder. AB - The situations in which the first panic attack occurred were investigated in 44 patients affected by panic disorder. Although the first panic attack was reported to be unexpected and no avoidance was present before it, 75.8% of patients (N = 22) with panic disorder with agoraphobia had their first panic attack in phobogenic situations, compared with 20% of patients (N = 3) with panic disorder without agoraphobia. PMID- 1590503 TI - Changes in DSM-III-R axis II diagnoses following treatment of obsessive compulsive disorder. AB - Seventeen patients with obsessive-compulsive disorder and concomitant personality disorders were treated with pharmacologic and/or behavioral therapy and reassessed after 4 months. Nine of the 10 patients who responded to treatment for obsessive-compulsive disorder no longer met criteria for a personality disorder. Of the seven nonresponders, five continued to meet criteria for a personality disorder. PMID- 1590504 TI - Final Exit as a manual for suicide in depressed patients. PMID- 1590505 TI - Clomipramine and a case of exhibitionism. PMID- 1590506 TI - Potential interaction of LSD and fluoxetine. PMID- 1590507 TI - Neuroleptic malignant syndrome induced by low-dose haloperidol. PMID- 1590508 TI - Distortion of racial identity and psychosis. PMID- 1590509 TI - Does the end justify the means? PMID- 1590510 TI - Diminishing toxic effects of lithium administration. PMID- 1590511 TI - Hysterectomy in patients with panic disorder. PMID- 1590512 TI - Freud and homosexuality. PMID- 1590513 TI - The mind-body problem. PMID- 1590514 TI - On kleptomania. PMID- 1590515 TI - Suicidality and the young. PMID- 1590516 TI - Fluoxetine and serotonin in autism. PMID- 1590517 TI - Elevated cortisol concentrations and the diminished prolactin response to fenfluramine. PMID- 1590518 TI - Borderline personality disorder and depressive disorder. PMID- 1590519 TI - Winter seasonal affective disorder. PMID- 1590520 TI - Part II of the ABPN certification examination. PMID- 1590521 TI - Part II of the ABPN certification examination. PMID- 1590522 TI - State profile in low-risk pre-term infants: a longitudinal study of 7 infants from 32-36 weeks of postmenstrual age. AB - Spontaneous motor behaviour was longitudinally studied in 7 low-risk preterm infants. The object of this study was to determine whether or not certain recognizable behavioural states exist between 32 and 36 weeks postmenstrual age (PMA), in order to have a well defined recognizable pattern of behaviour during which the preterm infant can be clinically examined. The criteria used to define a behavioural state were: eyes open/closed; crying present/absent; gross body movements present/absent; and respiration regular/irregular. A total of 35 videotapes were made (total time, 99 hours and 25 minutes). For analyzing the data, one second and three-minute windows were used. Our data provide convincing evidence that spontaneous behaviour of preterm infants of 32-36 weeks of PMA can be classified into behavioural states. The variables gross body movements and respiration, are not independent ones. The observed states can be used as a defined clinical condition during which the preterm infants can be clinically examined. PMID- 1590523 TI - Assessment of upper and lower extremity movements in hemiplegic children. AB - Upper and lower extremity movements were assessed in 26 children with spastic hemiplegia according to the modified Brunnstrom method. Of the upper extremity movements, supinating the forearm was most difficult, followed in order by pronating the forearm, flexing the shoulder to 90 degrees, flexing the shoulder to 180 degrees, abducting the shoulder to 90 degrees or putting the hand on the lumbar spine, putting the hand behind the ipsilateral ear (flexor synergy), and putting the hand on the contralateral knee (extensor synergy). The extensor and flexor synergies were easier than the other movements in the hemiplegic children as well as in hemiplegic adults, but the order of difficulty in the other movements in children was not the same as in adults. The difficulty in the lower extremity movements was uniform in the subjects. None of the children could dorsi flex the ankles and many could not rotate the hips internally. A small number of the children could not flex the knees or perform straight leg raising. All children could flex the hips and knees, extend the hips and knees, and abduct the hips. The difficulty in isolated hip abduction and flexion was less prominent in the hemiplegic children, compared to in hemiplegic adults. PMID- 1590524 TI - Celiac disease, posterior cerebral calcifications and epilepsy. AB - Ten patients (5 males) affected by epilepsy with cerebral calcifications of unknown etiology mainly located in the posterior regions were subjected to a battery of tests including an intestinal biopsy. Our aim was to establish whether or not the patients also suffered from celiac disease. Celiac diseases was found in 6 patients. This result and the individual cases reported in the literature suggest that this triad of diseases (celiac disease, posterior cerebral calcifications and epilepsy) are casually related. The same HLA phenotype was found in all 10 patients, i.e., including the cases without celiac disease, suggesting an underlying disorder of the immune system. Our results emphasize that particular attention should be paid to a search for celiac disease in all patients with epilepsy and posterior cerebral calcifications. PMID- 1590526 TI - Pelizaeus-Merzbacher disease: cellular hypersensitivity to ultraviolet light. AB - We report two connatal cases of Pelizaeus-Merzbacher disease (PMD) with cellular ultraviolet (UV)-hypersensitivity. We studied the UV-sensitivity of cultured fibroblast cells derived from these PMD cases, as compared with UV-sensitive Cockayne syndrome (CS) and xeroderma pigmentosum (XP) cells as positive controls. The ability of the PMD cells to form colonies after UV irradiation was intermediate between those of CS cells and normal controls. There were no differences in both colony-forming ability after x-ray irradiation and unscheduled DNA synthesis (UDS) activity after UV irradiation between the PMD cells and the control cells. These cytological results suggest the possibility that a DNA defect might be involved in PMD. PMID- 1590527 TI - Neonatal cerebral infarction: symptoms, CT findings and prognosis. AB - In a retrospective multi-center study, we investigated eighteen infants with unilateral cerebral infarctions confirmed by computed tomography (CT) scans. The initial symptoms were observed in all the patients between 0 and 3 days of age. Convulsions or apneic attacks were the initial symptoms in all but one. Only 4 patients had complicated obstetric histories and none showed polycythemia or electrolyte abnormalities. All of the initial CT scans revealed unilaterally localized hypodense areas. In 10, the initial CT scans were performed within 24 hours after the clinical onset. In 16, the lesions were within the territory of the middle cerebral artery, 9 of which also involved the cortico-spinal tract (CST). In the remaining 2 patients, the lesions were located within the territory of the posterior cerebral artery. None of the 9 patients without CST involvement developed hemiplegia, whereas 5 (56%) of the 9 with CST involvement had hemiplegia, which is a fairly low incidence compared with that in adult cases. This difference was thought to be related to neonatal brain plasticity. PMID- 1590525 TI - The carbohydrate deficient glycoprotein syndrome in three Japanese children. AB - We describe 3 children (from two families) with a multisystemic disorder characterized by mental retardation, nonprogressive ataxia, polyneuropathy, hepatopathy during infancy and growth retardation. Due to the clinical similarities to a recently recognized disorder associated with carbohydrate deficient transferrin, we examined serum transferrin by means of isoelectric focusing, and found increases in disialo transferrin and asialotransferrin. Removal of sialic acid with neuraminidase revealed the same transferrin phenotypes as in their parents. Similarly, carbohydrate-deficient fractions of serum alpha 1-antitrypsin were also detected. Therefore, the diagnosis was made of the recently identified carbohydrate-deficient glycoprotein syndrome. This is a genetic disorder with distinctive clinical features and multiple carbohydrate deficient glycoproteins. These seem to be the first reported Japanese patients with this syndrome. PMID- 1590528 TI - Three types of hyperthermic seizures in rats. AB - Three types of rat hyperthermic seizures were observed. The first comprised generalized clonic convulsions preceded by intermittent myoclonus. Ictal EEG showed diffuse intermittent spikes and sequential rapid spike-wave bursts (type 1 seizures). In the other types of seizures, the paroxysmal discharges originated in the occipital region without (type 2a seizures) or with (type 2b seizures) secondary generalization. Type 2a seizures involved no convulsive movement whereas type 2b seizures involved clonic convulsions. The threshold temperatures for type 1, 2a and 2b seizures were 44.1 +/- 0.60, 40.9 +/- 1.47 and 42.1 +/- 0.75 degrees C, respectively. Of these seizures, the type 2 seizures (2a and 2b) did not severely affect the general condition of rats and thus may be an appropriate model for the investigation of febrile seizures. PMID- 1590529 TI - A neuropathological study of a case of the Prader-Willi syndrome with an interstitial deletion of the proximal long arm of chromosome 15. AB - An autopsy case, a 6-month-old girl, with an interstitial deletion of the long arm of chromosome 15;del(15)(q11.1q12) was reported. Muscle hypotonia, poor sucking and intermittent ocular deviation were noticed soon after birth. She also exhibited external features peculiar to the Prader-Willi syndrome (PWS). The muscle hypotonia persisted and head control was not achieved. She died at the age of 6 months due to bronchopneumonia. G-banding analysis of prometaphase chromosomes revealed a deletion of chromosome 15. Bronchopneumonia of the lungs and fatty metamorphosis of the liver were found. Neuropathological anomalies recognized were; disturbed undulating structures, resembling cortical micropolygyria and pachygyria, in the dentate nucleus and the inferior olivary nucleus, grumose degeneration of the nerve cells in the dentate nucleus, and heterotopia of middle-sized neurons in the cerebellar white matter. No abnormalities were observed in the hypothalamus-pituitary system. In some autopsy cases of PWS, cerebellar lesions have been reported. These might be related to the muscle hypotonia in PWS. PMID- 1590530 TI - A neuropathological study of early onset Cockayne syndrome with chromosomal anomaly 47XXX. AB - We present the clinical and neuropathological findings in a female patient with early onset Cockayne syndrome and a chromosomal anomaly (47XXX). The girl was the only child of healthy, unrelated parents. She was born with a birth weight of 1,930 gm. She had progeroid facial features with bilateral cataracts. A diagnosis of 47XXX was made on the basis of a chromosomal study. Physical shortness became increasingly prominent while her weight remained stationary. Psychomotor retardation was noted, and she could never sit alone. A brain CT scan showed cerebral atrophy and calcification of the basal ganglia. Cultured skin fibroblast exhibited significant sensitivity to the ultraviolet light. She died from a chest infection at the age of 7 years and 4 months. Microscopically, the renal glomeruli showed diffuse sclerotic changes with thick capillary basement membranes. A neuropathological examination revealed a very small brain (295 gm), extensive myelin deficiency, gliosis in the white matter, and calcifications in the basal ganglia, and cerebral and cerebellar cortices. The loss of both Purkinje and granular cells was noticed in the cerebellar cortex. This is the first report of a case with the Cockayne syndrome and 47XXX, and the 47XXX in this patient seems to be coincidental. PMID- 1590531 TI - The Rett syndrome and CSF lactic acid patterns. AB - We investigated both blood and cerebrospinal fluid (CSF) lactate and pyruvate levels in seven girls with the Rett syndrome (RS) and evaluated the relationship between CSF lactate and pyruvate levels and the clinical manifestations, particularly seizures, anticonvulsant medication, and breathing dysfunction including breath holding, apnea and hyperventilation. Elevated lactate and pyruvate levels in CSF with normal serum lactate were found in two RS patients. Elevated CSF lactate correlated significantly with the clinical occurrence of hyperventilation (P0 = 0.048, Fisher exact probability). We measured native and dichloroacetate (DCA)-activated pyruvate dehydrogenase (PDH) complex activities in two patients (#1 and 2) using cultured lymphoblastoid cell lines which were transformed by EB virus and the results were normal. We also analyzed CSF citric acid intermediates from 7 RS patients including citric acid, cis-aconitate, alpha ketoglutarate, succinate, fumarate, malate and oxaloacetate. These concentrations were not significantly different from those control patients (N = 21). An elevated lactate level may be a clue to clarify the etiology of RS. PMID- 1590532 TI - Amniotic tissue transplantation: clinical and biochemical evaluations for some lysosomal storage diseases. AB - Amniotic epithelial cells has been used for transplantation in patients with lysosomal storage diseases as an enzyme replacement therapy. But its clinical effect is still the question under debate. We performed amniotic tissue transplantation on patients with different lysosomal storage diseases: one with Tay-Sachs disease, one with juvenile Gaucher disease and one with juvenile metachromatic leukodystrophy. The patient having juvenile Gaucher disease received this grafting twice. Objective clinical improvement was observed in the first trial where this patient showed an increase of soluble beta-glucosidase one week after implantation. No clinical or biochemical changes were seen in the other patients. Although there are some advantages to amniotic tissue transplantation, original methods should be modified to cell transplantation in order to avoid graft-versus-host reaction which could happen in repeated implantation. PMID- 1590533 TI - Alcohol use and dependence among employed men and women in the United States in 1988. AB - This paper provides estimates of alcohol consumption and alcohol dependence among employed men and women in the United States. Data from the 1988 National Health Interview Survey indicate that the percentages of drinkers in white-collar occupations are higher than the percentages of drinkers in blue-collar occupations among both men and women; however, the men and women in blue-collar occupations who drink have a higher average daily consumption than drinkers in white-collar occupations. DSM-III-R criteria were used to classify respondents as alcohol-dependent. Consistent with an earlier survey of employed adults in Detroit, the prevalence of alcohol dependence is highest in certain blue-collar occupations (craftsmen, laborers, and service workers among men; machine operators, laborers, and service workers among women). Directions for further research on the occupational and drinking experiences of employed men and women are discussed. PMID- 1590534 TI - Life transitions, work, and alcohol: an overview and preliminary data. AB - The interrelations between age, life transitions, drinking, and work roles are considered. Increased focus of age-related research on employed adults is suggested. The relevance of concepts of age stratification and life transitions is discussed. Data from an ongoing study of the clients of employee assistance programs are presented to demonstrate relationships between age, job characteristics, and drinking problems. PMID- 1590535 TI - Gender-role attitudes, job competition and alcohol consumption among women and men. AB - Attempting to account for greater alcohol consumption among women, social scientists have argued that traditional gender roles and gender-role attitudes concerning the division of labor in the family have provided women with a moral or cultural protection against heavier drinking but that the "breakdown" of this protection has allowed for greater alcohol use. This paper assesses the breakdown argument using data from two representative samples: a sample of 12,069 young adults in the United States and a sample of 1,367 employed men and women in metropolitan Detroit. Our analysis indicates that among young women the nontraditional role of employment and nontraditional gender-role attitudes concerning responsibilities for household labor and child care are associated with greater alcohol consumption. However, among the employed, our analysis indicates that it is not nontraditional women and traditional men but rather traditional women and nontraditional men who have greater alcohol use--it is the women and men who believe that they have substantial obligations at home and who have intense competition at the workplace that consume a greater quantity of alcohol. PMID- 1590536 TI - Occupational stress, psychological vulnerability and alcohol-related problems over time in future physicians. AB - This paper elaborates the conceptual frameworks and major results to date from an ongoing longitudinal study of alcohol problems in male and female future physicians. A medical student cohort was surveyed at medical school entrance and in the 2nd and 3rd years of training. Relative to life span developmental orientations, a sizable proportion of premedical school problem drinkers "matured out" of their earlier patterns after entrance into occupational training roles. Relative to occupational selection versus stress perspectives, medical school problem drinkers were equally divided between those manifesting onset prior to the initiation of training versus those manifesting onset during medical training. Overall, both male and female problem drinking declined during the preclinical years (in contrast to premedical school levels) but manifested a trend in the direction of a reversal of the previous decline after the initiation of clinical training. The major psychosocial predictor of alcohol abuse during clinical training involved social-relational deficits or narcissistic personality styles. Moreover, this relationship was mediated by social support deficits and patient care-related stressors. This cohort is currently being re-surveyed in the last year of medical school and will be followed again during residency training. PMID- 1590537 TI - Women, work, and alcohol: failures of simple theories. AB - When trying to explain how women's employment affects their drinking behavior, oversimplified theories produce weak and inconsistent results. Recent research casts doubt on any simple ideas that paid employment is hazardous for women's mental health and drinking, or that paid employment is beneficial for women's mental health and drinking, or that stressful jobs increase women's risks of problem drinking. Improved, more complex theories could specify which women will modify their drinking behavior as a result of particular employment experiences, predict interaction effects of employment conditions with other aspects of women's lives, and explain how employment may create a context where other variables may increase or reduce risks of problem drinking. PMID- 1590538 TI - Minimization of workplace alcohol problems: the supervisor's role. AB - Based on findings from an ethnographic analysis of an assembly plant in a large manufacturing industry, this paper delineates a conceptual framework for "minimization" that proposes to explain the interactional processes leading to systemized weakening of alcohol problem awareness and action in the unionized workplace. In the course of 50 semi-structured interviews and observations with union representatives and management, the role of the first-line supervisor emerged as pivotal to minimization. Individual case studies from the ethnography and responses from a survey sample of 1000 employees are used to illustrate how goals and processes of the workplace culture impede forthright action and clear lines of decision making on alcohol issues. PMID- 1590539 TI - The workplace and problem drinking as seen by two novices. AB - Based on a selective review of the occupational alcoholism literature, a number of difficulties with the research regarding the effects of the workplace on problem drinking were identified. The identification of these difficulties led to an alternative model being proposed. The alternative emphasizes interactions between predispositional factors and the workplace and does not advocate continuing to search for main effects of the workplace on problem drinking. The paper closes with 10 recommendations for future research. PMID- 1590540 TI - Life strains, alienation, and drinking behavior. AB - This paper examines the effect on drinking behavior of chronic strains deriving from on-going work circumstances, and intermittent strains deriving from transitions imposed by life events: unemployment; economic strain; and stress experience (e.g., death in the family, serious illness, etc.). The respondent's personal resources for coping with these life strains are also examined by way of three measures of alienation: the sense of powerlessness, self-esteem, and social integration. The interaction of situational strains and individual alienation is a primary focus. Regression and covariance analyses, using a sample of some 500 male respondents, indicate that (1) unemployment in itself is of relatively little consequence, (2) powerlessness is the most consistent predictor of alcohol use and abuse, and (3) the combination of stress experience and high powerlessness typifies those who are most vulnerable to high drinking quantity and drinking problems. PMID- 1590541 TI - Cognitive functioning, ASP, and family history of alcoholism in young men at risk for alcoholism. AB - Previous research has suggested that individuals with a family history of alcoholism may have cognitive deficits that predate, and possibly predispose, to the onset of alcoholism. However, these deficiencies may result from other factors, e.g., comorbid psychopathology. The current study investigated the neuropsychological functioning of young adult males at high risk for alcohol abuse due to a family history of alcoholism (FH) and/or a personal history of antisocial personality disorder (ASP). A family history of alcoholism (FH+) alone was not associated with neuropsychological impairment. Subjects with ASP, however, exhibited some difficulty with higher level motor control and with verbal concept formation compared with nonASP subjects. No clear pattern of FH x ASP interaction was evident in the measures examined. These findings suggest that previous findings suggesting cognitive deficiencies in FH+ individuals may have been related to a failure to consider co-morbid ASP. The deficits exhibited by the ASP subjects may reflect both reduced inhibitory control and a deficiency in higher level verbal skills. These deficiencies may leave ASP individuals less capable of utilizing higher level language skills to regulate behavior. PMID- 1590542 TI - DSM-III-R and the proposed DSM-IV alcohol use disorders, United States 1988: a nosological comparison. AB - The purpose of the present study was to compare DSM-III-R and the proposed DSM-IV diagnostic criteria for alcohol abuse and dependence in a representative sample of the United States general population. Alcohol abuse and dependence diagnostic categories were contrasted in terms of prevalence and overlap. The prevalence of DSM-III-R diagnoses of alcohol abuse and dependence combined (8.63%) was greater than the corresponding DSM-IV diagnoses (6.00%). Disaggregation of abuse and dependence diagnoses showed that the major discrepancy between the classification systems resided between the abuse categories. Reasons for the discrepancies are discussed in terms of differences in the content of the DSM-III-R and DSM-IV abuse categories, in the relationship that each abuse category shares with its respective dependence category, and the impact of the DSM-III-R duration criterion. PMID- 1590543 TI - Characteristics of a new urine, serum, and saliva alcohol reagent strip. AB - We have tested an ethanol reagent strip developed at the Addiction Research Foundation of Ontario. Alcohol dehydrogenase and nicotinamide adenine dinucleotide, in the presence of pyrazole, react with ethanol to yield acetaldehyde plus reduced nicotinamide adenine dinucleotide. The latter reduces iodonitrotetrazolium chloride in the presence of diaphorase, generating an intense red color. The rate of color development is proportional to the concentration of ethanol. Color is compared at a specific time against a calibrated color scale ranging from green (negative) to red, representing alcohol concentrations of 0, 25, 50, 100, 200, and 400 mg/dl (0-0.4%; 0-87 mmol/liter). We were able to interpolate the color observed between the calibrated blocks. When tested on urine, serum/plasma, and saliva, ethanol concentration determined by the reagent strip correlates well with ethanol concentration as determined by gas chromatography or by automated enzymatic analysis (r = 0.92-0.98, p less than 0.001; slope 0.83-1.16). The reagent strip was shown to be used appropriately by nonexperienced individuals following a 1-min explanation (reagent strip values, r = 0.92; p less than 0.001, slope = 0.97, versus gas chromatography). The reagent strip does not react with methanol (wood alcohol), isopropanol (rubbing alcohol), and ethylene glycol (antifreeze) often found in accidental poisonings. In 379 clinical samples obtained without exclusion criteria from 12 hospital emergency rooms and a liver clinic, the sensitivity of the reagent strip in detecting ethanol was 98%. Specificity was 99%. The reagent strip was found to have virtually unlimited stability under refrigeration (4 degrees C) and to be stable for 3 to 4 months at room temperature (22-23 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590544 TI - Neuroendocrine, fluid balance, and thirst responses to alcohol in alcoholics. AB - This study simultaneously evaluated multiple circulating neurohormones, osmolality, thirst, and fluid balance in eight actively drinking, alcoholic males and seven controls before and 12 hr after an ethanol challenge. Basal levels of serum osmolality and thirst were significantly higher in alcoholics compared with controls, yet actively drinking alcoholics at the start of the study had normal vasopressin (AVP) levels, plasma angiotensin II (Ang II), plasma renin activity, plasma aldosterone (Aldo), and plasma catecholamines. In response to ethanol, serum osmolalities rose significantly higher while plasma AVP levels became significantly suppressed in alcoholics. After the ethanol stimulus, plasma Ang II levels of alcoholics were significantly higher than those of controls at 11 AM (12.15 +/- 4.49 vs. 1.83 +/- 0.6 pg/ml, p less than 0.02) and 12 noon (14.93 +/- 6.81 vs. 1.37 +/- 0.17 pg/ml, p less than 0.04). Neither plasma renin activity nor Aldo changed in accordance with the elevated plasma Ang II in alcoholics. Diuresis in the alcoholics, assessed by the sum of urine output following the challenge dose, was significantly less than that of controls. Thirst scores and fluid intakes after the ethanol challenge did not differ between alcoholics and controls. The lack of an Ang II-mediated increase in plasma Aldo or thirst response suggests that ethanol may have a specific blunting effect on Ang II receptors. This study demonstrates that ethanol can be used as a provocative test in chronic alcoholics to uncover aberrant hormonal responses for two systems, namely, Ang II and AVP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590545 TI - Consistency and change in patterns of social drinking: a 6-year follow-up of the Finnish Twin Cohort. AB - In 1975 and again in 1981, all adult twins in the population-based Finnish Twin Cohort were administered postal questionnaires yielding data on self-reported frequency and quantity of alcohol use. The longitudinal results provide information on the age-to-age stability of social drinking patterns among 13,404 (twin) individuals aged 18 to 43 at baseline; model-fitting the cross-temporal consistency of the twins' reported alcohol use yields unique estimates of the contribution of genetic and environmental factors to their individual age-to-age stabilities. Mean consumption levels did not change between 1975 and 1981. Patterns of social drinking were more stable in older (aged 24-43 at baseline) than younger (aged 18-23 at baseline) adult twins, and were more stable among men than women. Heritabilities were significant at both baseline and follow-up for all three alcohol measures in both genders and both age groups, with a median magnitude of 0.48. Both longitudinal genetic and environmental covariances were significant, and both were generally higher among older pairs. Genetic covariances (median magnitude = 0.68) were significantly higher than environmental covariances (median = 0.36). Analyses of absolute changes in alcohol use revealed heritable influences on the disposition to change. We conclude that genes contribute to both consistency and change in patterns of alcohol use from early to midadulthood. PMID- 1590546 TI - A rating scale for assessment of alcohol withdrawal psychopathology (AWIP). AB - For patients in alcohol withdrawal, there are several scales designed to assess physiological disturbances, but there seems to be a lack of scales for assessment of psychopathology. To develop and evaluate a rating scale for psychopathology, items from the Comprehensive Psychopathological Rating Scale (CPRS) were selected, and patients meeting the DSMR-III-R criteria for alcohol dependence (303.90) were rated on these items. The patients were divided into two groups according to the length of time passed since their last period of alcohol consumption. The groups are referred to as the group (n = 53) in early withdrawal, rated daily during 1 week and the group (n = 13) in late withdrawal, rated once a week for 7 weeks. To justify inclusion in the new scale, items had to either indicate psychopathology in at least half of the patients in one of the groups in withdrawal, or be sensitive to changes over time at a 0.1% level of significance. Seventeen items fulfilled one of these criteria. The scale was tested for inter-rater reliability in a new sample of patients (n = 30) in early withdrawal. Inter-rater reliability, as well as internal consistency, was found satisfactory. This new scale, capable of identifying psychopathology and changes over time, may be used alone or together with physiological scales to identify subgroups of patients undergoing withdrawal. PMID- 1590547 TI - Alcohol expectancies and behavioral and emotional responses to placebo versus alcohol administration. AB - Forty normal drinking males were recruited for a study of "responses to alcohol." Following the completion of an alcohol use questionnaire that included measures of expectancies of alcohol effects, subjects were randomly assigned to either receive the actual 0.6 g/kg dose of ethanol to bring their peak blood alcohol concentration (BAC) to near 0.075 g/dl or to receive a placebo dose. Neither the subject nor the tester was aware of the condition to which the subject has been assigned. Prior to dosing and at repeated 1/2-hr intervals following dosing, subjects were tested on a battery of motor coordination, perceptual speed, reaction time, and mood measures. Significant alcohol effects were found for several measures, but the only significant interaction of individual differences in expectancies of alcohol effects with alcohol dosing occurred for self perceived intoxication. Subjects who expected more disinhibition after alcohol dosing and who were administered alcohol reported more intoxication than those expecting less disinhibition, while no expectancy effect was found for subjects administered the placebo. PMID- 1590549 TI - Obsessive and compulsive characteristics of craving for alcohol in alcohol abuse and dependence. AB - The purpose of this study was to quantify the extent to which subjective ratings of craving for alcohol in the alcohol-abusing or dependent person (herein, alcoholic) correlate with measurable and specific characteristics of obsessions and compulsions. The Yale-Brown Obsessive Compulsive Scale modified to reflect obsessionality and compulsivity specifically related to heavy drinking (Y-BOCS hd) was used for this purpose. Highly significant correlations were found in the alcoholic population (n = 62) between subjectively rated craving for alcoholic beverages and several of the Y-BOCS-hd questions regarding alcohol-related thoughts and drinking behavior. Additionally, mean craving scores were considerably greater in the alcoholic population than in the matched control population (n = 62). The data suggest that craving shares specific features in common with the obsessions of obsessive-compulsive disorder and that the existence of craving is dependent on the presence of obsessive thoughts about drinking. Positive correlations between craving and measures of compulsive drinking behavior also were found; compulsive drinking behavior, however, may reflect the consequences of craving rather than a fundamental characteristic of craving itself. The data show that despite difficulties in defining the term craving, it is clearly a phenomenon that is experienced or endorsed by most alcoholic subjects and is not by most persons who do not abuse alcohol. PMID- 1590548 TI - Obsessive and compulsive characteristics of alcohol abuse and dependence: quantification by a newly developed questionnaire. AB - The purpose of the this study was to develop an instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in subjects who abuse or are dependent on alcohol, and to quantify the extent to which drinking-related thought and behavior in these subjects resemble the obsessions and compulsions seen in obsessive-compulsive disorder (OCD). To achieve these goals, the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was modified to reflect obsessionality and compulsivity specifically related to heavy drinking rather than to obsessions and compulsions generally. The modified Y-BOCS (Y-BOCS-hd) was administered to 62 subjects satisfying DSM-III-R criteria for alcohol abuse or alcohol dependence and 62 matched normal controls. The data showed that the Y-BOCS-hd is a sensitive and specific instrument for measuring the obsessive and compulsive characteristics of drinking-related thought and behavior in alcohol-abusing and alcohol-dependent populations, and that there are specific and quantifiable similarities between these characteristics and the obsessions and compulsions of OCD. The data also indicated that the Y-BOCS-hd may be a useful screening instrument for the presence of alcohol abuse and dependence. PMID- 1590550 TI - Alcohol dehydrogenases in the brain of mice. AB - Alcohol dehydrogenase (ADH) phenotypes were investigated in the brain of 15 different inbred mice by isoelectric focusing followed by staining of enzyme activities. The Class III ADH activity was detected in all the strains studied, whereas the Class II ADH activity was found only in few strains (including the alcohol-preferring strain--C57BL/6J) having the "a" allele (ADH-C2(2)) for this isozyme in stomach. The inbred strains having the "b" allele (ADH-C2(1)) for the Class II ADH in stomach (including the alcohol avoiding strains--BALB/c, CBA/H, C3H/He, DBA/2J, and SJL/J) demonstrated null variant for this phenotype in their brain. The Class I ADH activity was very low or absent in the brain extracts of all the strains studied. The ADH activities were confined to the cytosolic fractions of brain and were higher in the extracts of cerebral hemispheres than in cerebellum. The genetic linkage studies showed that the locus for the brain Class II ADH is closely linked to the "Adh gene complex" on chromosome 3 of mice. PMID- 1590551 TI - The effect of ethanol metabolism on ferritin uptake by freshly isolated rat hepatocytes: is acetaldehyde responsible for this alteration? AB - Alcohol abuse is associated with disturbances to iron metabolism in man, ranging from anemia to siderosis. Also seen in these patients are increased serum ferritin levels. Since the liver not only stores iron in cytosolic ferritin, but has also been shown to take up this molecule from the plasma by an active transport mechanism, it has been suggested that the iron in this circulating ferritin may contribute to the increased incidence of siderosis seen in alcoholics. As part of an ongoing study of these disturbances, using a rat model, we have examined the uptake of ferritin by freshly isolated hepatocyte suspension to test the hypothesis that increased hepatocyte uptake of ferritin iron contributes to the siderosis seen in some alcoholics. Incubation of hepatocytes in the presence of ethanol resulted in a progressive reduction in uptake with increasing alcohol concentration, from 1.23 +/- 0.05 ng of ferritin/10(6) cells/min to 0.65 +/- 0.02 ng/10(6) cells/min (mean +/- SD) at an ethanol concentration of 100 mM. 4-Methylpyrazole (0.1 mM) restored 70% of this activity, but higher concentrations also decreased ferritin uptake in the absence of ethanol. The addition of 5 microM cyanamide decreased ferritin uptake slightly in the presence of ethanol (0.82 +/- 0.04 ng of ferritin/10(6) hepatocytes/min vs. 0.86 +/- 0.03 ng/10(6) cells/min for ethanol alone), while having no effect in the absence of ethanol (1.01 +/- 0.04 vs. 1.12 +/- 0.05 ng/10(6) cells/min). Preincubation of the hepatocytes with acetaldehyde resulted in a dose-dependent reduction to a maximum reduction of approximately 25% at 300 microM acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590552 TI - Effects of alcohol on intrauterine oxygen tension in the rat. AB - The effects of alcohol on the availability of oxygen within the uterine lumen of rats were determined on Day 4 of pseudopregnancy. Intraluminal oxygen tension (pO2) was measured in vivo in anesthetized rats using a 22-gauge polarographic oxygen sensor. Intrauterine pO2 was measured for 15 min before and after intravenous injection of alcohol (1.0 g/kg: 100% ethanol/saline, 1:2v/v) or vehicle (physiological saline). Alcohol administration increased mean intrauterine pO2 (mm Hg) from a pretreatment level of 28.3 +/- 2.8 to 38.7 +/- 3.8 mm Hg (p less than 0.05, n = 10) at 15 min postinjection. The rapid rise in oxygen tension was accompanied by increased frequency of fluctuation (peaks/hr) in intraluminal pO2 (prealcohol: 64.2 +/- 8.8 vs. postalcohol 96.0 +/- 7.7 peaks/hr; (p less than 0.05, n = 10). Injection of saline did not alter any aspect of intrauterine pO2. During the period of measurement of luminal pO2, blood alcohol levels increased from 0 during pretreatment to 106 mg% within 10 min of injection. These results indicate that alcohol increases the availability of oxygen within the uterus during the time of endometrial sensitivity to deciduogenic stimuli and blastocyst implantation. PMID- 1590553 TI - Attenuation of alcohol preference in alcohol-preferring rats by a novel TRH analogue, TA-0910. AB - Experiments were performed to characterize the acute effect of different doses of a novel thyrotropin-releasing hormone (TRH) analogue (TA-0910) on ethanol intake in rats. Selectively bred alcohol-preferring (P) rats received a single intraperitoneal injection of normal saline or 0.083, 0.25 and 0.75 mg/kg of TA 0910 at 9:30 AM, and their consumption of ethanol, water, and food was measured for 24 hr. TA-0910 dose-dependently attenuated ethanol intake and commensurately increased water consumption. Only the highest dose of TA-0910 increased the total caloric intake. TA-0910 did not affect the pharmacokinetics of ethanol. These findings indicate involvement of TRH systems in ethanol preference and suggest that centrally acting TRH analogues may be therapeutic in the treatment of alcoholism. PMID- 1590554 TI - Ethanol-induced suppression of cell-mediated immunity in the mouse. AB - Among its many effects on multiple organ systems, ethanol abuse also elicits potent immunomodulatory effects as well. Increased susceptibility to disease as well as increased severity in infection is well documented in alcoholics and may be related to an altered immune response. A mouse model has been developed in which C57Bl/6 mice are fed a nutritionally adequate liquid diet in which ethanol provides 27% of total calories (3.75% ethanol) in order to examine the effects of short-term, low dose ethanol administration on cell mediated immunity. All mice were evaluated for percentage of plasma ethanol, impaired motor skills and impaired delayed type hypersensitivity to sheep erythrocytes. Animals fed the ethanol diet for 5, 10, or 15 days evidenced plasma ethanol concentrations between 0.13% and 0.23% as well as significantly impaired motor skills. Mice maintained on the ethanol diet 8 days prior to erythrocyte sensitization and on the 6 days between sensitization and challenge demonstrated a significant reduction of 58% in footpad swelling. Moreover, mice fed ethanol for only the 6 days between erythrocyte sensitization and challenge also demonstrated a significant decrease of 35% in this delayed type immune response. However, animals administered ethanol prior to sensitization and then switched to control diet between sensitization and challenge evidenced a normal cell-mediated immune response to the sheep erythrocytes. Thus, it appears that the critical time of low dose ethanol-induced immunosuppression is between immunogen sensitization and challenge. PMID- 1590555 TI - The discriminative stimulus properties of acute ethanol withdrawal (hangover) in rats. AB - Twenty male Sprague-Dawley rats were trained to discriminate pentylenetetrazole (PTZ, 15 mg/kg, intraperitoneally) from saline (SAL) under a drug discrimination procedure. Test sessions were conducted with 10 randomly selected subjects. Tests with various doses of PTZ resulted in a dose-dependent increase in the percentage of total session responses emitted on the PTZ-appropriate lever without a significant change in response rates across a wide range of test PTZ doses. Rats did not generalize the PTZ stimulus to ethanol (ETOH) up to ETOH test doses that completely suppressed responding. High acute ETOH doses (2, 3, and 4 g/kg) administered at various time points prior to discrimination test sessions engendered responding on the PTZ-appropriate level in a quantitative fashion, that was dose- and time-dependent. This acute ETOH delayed effect from these high doses replicates our previously published study using a Drug 1-Drug 2 discrimination task with Chlordiazepoxide and PTZ. More importantly, we suggest that the present behavioral assay may be a sensitive animal analogue of human "hangover" phenomena. PMID- 1590557 TI - Ethanol stimulates immunoreactive endothelin-1 and -2 release from cultured human umbilical vein endothelial cells. AB - The present study employed enzyme-immunoassay to examine the effect of ethanol on endothelin-1 and/or -2(ET1 + 2) release from human umbilical vein endothelial cells. Thirty minutes of exposure to ethanol increased the release of immunoreactive ET1 + 2 from cultured endothelial cells in a dose-dependent manner. However, ethanol at concentrations of less than 400 mM did not induce any LDH release from the endothelial cells. Trypan blue exclusion test revealed that 400 mM solution of ethanol decreased the cell viability to 7.7%. Thus, ethanol was found to directly stimulate ET1 + 2 release from cultured human umbilical vein endothelial cells. This reaction of vascular endothelial cells against ethanol may be related to ethanol-induced cardiovascular diseases such as hypertension, myocardial infarction and stroke, as well as fatal alcohol syndrome. PMID- 1590556 TI - Serum type I collagen and N-terminal peptide of type III procollagen in patients with alcoholic liver disease: relationship to liver histology. AB - This study compared, in patients with alcoholic liver disease, the serum concentration of N-terminal peptide of type III procollagen and of a novel serum marker, type I collagen, with liver histological data and assessed the role of these markers in the diagnosis and follow-up of liver changes. Ninety-six patients (mean age 51 years, 61 men and 35 women) were included. All had alcoholic liver disease diagnosed on usual clinical, biochemical, and histological criteria. Two histological scores, one for alcoholic hepatitis and one for fibrosis, were established. Serum N-terminal peptide of type III procollagen and type I collagen were assayed by liquid phase radioimmunoassay. Significant correlations between serum type I collagen and score of fibrosis (r = 0.34, p less than 0.001) and between serum N-terminal peptide of type III procollagen and score of alcoholic hepatitis (r = 0.60, p less than 0.0001) were noted. There was no significant correlation between serum aminotransferases and the score of alcoholic hepatitis. In 25 patients with alcoholic hepatitis reassessed between 3 and 6 months, serum N-terminal peptide of type III procollagen significantly decreased (p less than 0.05) as did the score of alcoholic hepatitis, but serum type I collagen and the score of fibrosis were not modified. These serum markers of collagen metabolism could be useful for the assessment and follow-up in patients with alcoholic liver disease. PMID- 1590558 TI - One more look at alcohol consumption and risk of coronary disease. PMID- 1590559 TI - Another look at minimum drinking age laws and traffic accident involvement. PMID- 1590560 TI - CD8+ T cells in allergy. PMID- 1590561 TI - Allergens from rye pollen (Secale cereale). I. Study of protein release by rye pollen during a 19-hour extraction process. Allergen identification. AB - We have studied the proteins and allergens released by rye pollen in the course of a 19-h pollen incubation process. Nearly 40% of the total extracted proteins were collected during the first 5 min, and most of them had a molecular weight less than 28 kDa. Between 5 and 30 min, 15% of the proteins from total extract were released, showing in the SDS-PAGE analysis an increase in which components moved close to 30 kDa standard. From 30 min to 19 h several extracts were collected. Electrophoretical profile of components from these extracts reveals that bands moving below 28 kDa were practically absent and those of 28 and 23 kDa became very intense. At the end of the process there was a rise of 67 kDa proteins. Dot-immunobinding and immunoblotting techniques reveal that allergens leave the rye pollen, for the most part, after 5 min incubation and are proteins with 28 kDa, 33 kDa, 48 kDa and 67 kDa molecular weights. PMID- 1590562 TI - Allergens from rye pollen (Secale cereale). II. Characterization and partial purification. AB - Rye pollen was incubated for 30 min and proteins extracted at this time were collected as extract A (EA). The same pollen grains were resuspended in buffer and incubated for 18.5 h. Proteins extracted in this period were designated extract B (EB). Both extracts were subfractionated by DEAE ion-exchange chromatography and allergen presence in peaks detected by the dot-immunobinding technique. The results reveal that unretained proteins (peaks 1 and 2) and proteins eluted at 0.2 M NaCl from extract B contain the highest proportion of allergens. SDS-PAGE of chromatographic peaks showed that peak 2 from extract B contains a highly purified 28 kDa band. On the skin of allergic patients this band gave a stronger positive prick test than for the crude extract. PMID- 1590563 TI - Asthma: a disease remodeling the airways. PMID- 1590564 TI - Comparison of CLA with BPT, SPT, and RAST in children with asthma. AB - Bronchial provocation tests (BPT) with allergen extracts were performed in 82 children with asthma, and the results were compared with the chemiluminescent assay (CLA), the radio-allergo-sorbent-test (RAST) and skin prick test (SPT). It was found that CLA matched BPT with a concordance of 87% (77-93%), RAST with a concordance of 74% (64-83%) and SPT with 80% (70-88%). Most often, CLA and RAST gave similar results, although their classes did not match precisely. PMID- 1590565 TI - Yellow jacket allergy. Comparison of skin prick tests and intradermal tests with three different yellow jacket venom extracts. AB - The aim of the present study was to compare yellow jacket venom extracts from two different companies and to compare skin prick test (SPT) with intradermal test (IDT). IDT and SPT with yellow jacket venom (ALK and Pharmacia Reless) were performed on 54 yellow jacket allergic patients and 44 symptom-free volunteers. Venom was diluted to 300, 100, 10 and 1 microgram/ml for SPT and 10(0), 10(-1), 10(-2), 10(-3) and 10(-4) micrograms/ml for IDT, according to the manufacturers' instructions. Skin tests were performed on both forearms. Both extracts showed approximately the same relationship between sensitivity and specificity, but the Pharmacia Reless yellow jacket venom extract showed a 5-10 fold higher biological activity in both SPT and IDT. Thus yellow jacket venoms of ALK and Pharmacia Reless are not comparable in allergen activity at the same venom concentrations. Using extracts from the same company, SPT and IDT were comparable with regard to sensitivity and specificity at an allergen concentration 1000 times higher for SPT than for IDT. PMID- 1590566 TI - Allergy to honey: relation to pollen and honey bee allergy. AB - To identify the allergenic components of honey we studied 22 patients with a history of systemic allergic symptoms following honey ingestion. The group of honey-allergic patients was compared with three control groups: 10 subjects sensitized to artemisia, 10 with honey bee venom allergy and 10 without a history of atopy or bee sting reactions. The allergological tests included skin tests and RAST with three different kinds of Swiss honey (dandelion, forest and rape), pollen of compositae species, celery tuber, extract of bee pharyngeal glands, honey bee venom and bee whole body extract. The results show that 3/4 of honey allergics are sensitive to dandelion honey and 13 of 22 also to compositae pollen. Nine of the honey allergic patients were sensitized to honey bee venom, 3 also to bee pharyngeal glands and to bee whole body extract. Analysis of diagnostic tests and RAST inhibition studies suggest that besides compositae pollen other allergens, most likely of bee origin are important. In honey allergics primary sensitization may be due either to the honey itself, to airborne compositae pollen or even to cross-reacting bee venom components. PMID- 1590568 TI - Concentration of airborne mite allergens (Der I and Der II) during sleep. AB - Using a low-noise air sampler and a sensitive radioimmunoassay, we measured the concentration of mite allergens in the air during sleeping with Japanese bedquilts (futon). The airborne allergen levels of Der I (Der p I plus Der f I) and Der II during sleep were 223 and 87.1 pg/m3 of air, respectively. These levels were about 10-fold higher than those during usual domestic life in the living room of the same houses. When the bedquilts were changed to new ones free of mite allergens, the airborne allergen levels of Der I and Der II were decreased to 11.5 and 12.0 pg/m3, respectively. This indicated that the mite airborne allergens during sleep were generated from the used bedding, not from the floor. We believe that exposure to airborne mite allergens during sleep might be an important factor in the development of mite allergies. PMID- 1590567 TI - PAF acether release on antigenic challenge. A method for the investigation of drug allergic reactions. AB - This study describes an in vitro method to evaluate a PAF acether release test (PART) from white blood cells after antigenic challenge. PAF acether activity of the supernatant was tested by platelet aggregation. The aggregating power was abolished by using SRI 63-441 (Sandoz), a PAF acether inhibitor. This method was applied to 57 patients with allergic or pseudo-allergic reactions to drugs by using different drug protein conjugates. The results of PART were evaluated in relation to the clinical history (score of imputability) and to other tests (skin tests, lymphocyte transformation tests (LTT), IgE-RAST). A good correlation was found between the release of PAF acether and a high predictability score: sensitivity 75%, specificity 83.8%. PART also correlated with skin tests (75% agreement, n = 60), with LTT (67.7% agreement, n = 74) and in 65.6% of cases with positive penicillin IgE-RAST (n = 32). This method brings a new possibility for the investigation of drug-allergic and pseudo-allergic reactions. PMID- 1590569 TI - Influence of the histamine control on skin reactivity in skin testing. AB - We investigated the effect of the histamine control (1 mg/ml) on the results of skin prick and intradermal testing with bee and wasp venom. Skin tests were done on the patients' forearms: on the right arm the histamine control and the bee venom dilutions, on the left arm the wasp venom dilutions only, at distances of 4 5 cm. In intradermal testing 11 (9%) of 122 patients showed a positive wheal and flare reaction to the bee venom solution positioned next to the histamine control. The subsequent solutions in higher concentrations did not produce any skin reactions. The results of intradermal testing with bee venom did not occur in intradermal testing with wasp venom or in skin prick testing with both allergens. Our results show clearly that in skin prick tests a distance of 4-5 cm is sufficient to avoid false positive skin reactions. However, using the same distance in intradermal testing showed that histamine affects the skin reactions produced by adjacent allergen solutions. Therefore false positive results may occur. PMID- 1590570 TI - Terfenadine in allergic chronic cough in children. PMID- 1590571 TI - Peranaesthetic anaphylactoid shock due to mannitol. PMID- 1590572 TI - [Therapeutic control of premedication with famotidine given on the evening before surgery for the prevention of pneumonitis in heart surgery patients]. AB - Pulmonary damage after aspiration of acid gastric content is one of the major risks of general anaesthesia. Antisecretory therapy with different H2-antagonists can effectively decrease the risk of aspiration. The effective dosage and the method and timing of administration remain unclear. PATIENTS AND METHODS. A series of 38 patients scheduled for elective cardiac surgery (coronary artery bypass graft) were premedicated at random at 10:00 p.m. on the evening prior to surgery with famotidine 40 mg and flunitrazepam 0.5 mg p.o. or with flunitrazepam alone. Continuous intragastric pH monitoring (720 values/h) with a combined glass electrode was started immediately after induction and continued for at least 12 h after surgery, in most cases up to extubation. The time periods analyzed were the first 30 min after induction, time of surgery, 12 h after surgery, and time of extubation. For each period the number of pH values less than 2.5 and pH less than 4, mean and median, and significance of differences were calculated. STATISTICS. Test statistics were evaluated using the Wilcoxon test and the Mann Whitney U-test. RESULTS. (see Table 1, Fig. 1). The mean time interval between oral premedication and induction of anaesthesia was 9.7 h. There were no differences between the groups concerning age and duration of surgery. The average age was 51 in the group of treated patients (n = 15) and 59 years in the control group (n = 23). The average duration of surgery was 3.36 h and 4.02 h. During induction and in the following 30 min, in the famotidine treatment group 28.7% of all pH values were pH less than 2.5, as against 45.4% in the control group (P = 0.08). Intraoperative values: 16.3% pH less than 2.5 against 24.7% (not significant); 12 h postoperative: 21.1% vs 17.8% and during extubation 40% vs 21% (not significant). During induction there were more pH values less than 2.5 in the control than in the treatment group (P = 0.08). Treated patients had nearly 30% pH values less than 2.5 and therefore, a persisting risk of acid aspiration. In both groups intragastric acidity decreased during surgery. Postoperatively there was no difference between the two groups, and during extubation more patients in the famotidine-treated group had values below pH 2.5. CONCLUSION. Prophylaxis of acid aspiration before, during and after cardiac surgery can be achieved by increasing the pH of the gastric content. The timing and the method of administration must be selected to a safe decrease in intragastric acidity before the induction of general anaesthesia. Famotidine 40 mg given orally at 10.00 p.m. on the evening before surgery is not a reliable means of decreasing intragastric acidity or, consequently, of preventing of acid aspiration syndrome. PMID- 1590573 TI - [Hepatic elimination of thiopental in heart surgery patients]. AB - Thiopental is a hypnotic drug that is widely used for the induction of anaesthesia. The mechanism of the short-term action is based on the rapid distribution of the drug, and in contrast to methohexital, the metabolism of thiopental is not relevant in use in conditions of operative anaesthesia. However, in neurotraumatology thiopental is frequently used as continuous infusion for several days to reduce cerebral metabolism. Under these circumstances, the elimination of thiopental becomes the most important factor for the duration of action. In order to clarify the relative contribution of the liver to the disposition of thiopental, hepatic blood flow was measured during the induction of anaesthesia and at sternotomy combined with the determination of plasma concentrations of the drug in arterial and hepatic venous blood, making it possible to calculate the hepatic and total plasma clearance of thiopental. METHOD. The study was thoroughly discussed and approved by the local ethics committee, and all patients gave informed written consent. The investigation was performed in 10 male patients (as detailed in Table 1), who had been referred for elective coronary artery bypass surgery. The determination of hepatic plasma flow was performed by the indocyanine green (ICG) infusion extraction technique using liver vein catheterization. Before induction of anaesthesia (MP1), after induction (MP2) and at sternotomy (MP3), hemodynamic data (heart rate, arterial pressure, cardiac output) were recorded and blood samples for the determination of hepatic plasma flow by the concentration of ICG were collected. Additionally, arterial and hepatic venous plasma concentrations of thiopental were determined by gas chromatography after induction until the extracorporeal circulation was started. Anaesthesia was induced with a bolus dose of thiopental 4 mg/kg body wt, fentanyl 7 micrograms/kg and pancuronium 0.1 mg/kg and maintained with a continuous infusion of fentanyl 20 micrograms/min and mechanical ventilation with O2/N2O at an FiO2 of 0.5. RESULTS. Median arterial pressure (MAP) decreased from 89 mmHg to 74 mmHg after induction and rose again to reach 104 mmHg at sternotomy. Cardiac output (HZV) also decreased from 6.17 l/min to 4.76 l/min after induction, but remained unchanged at sternotomy (Table 2). Hepatic plasma and blood flow showed no significant changes but tended to decrease after the induction of anaesthesia. Hepatic blood flow was constantly 26-28% of cardiac output. In the same way, intestinal oxygen consumption (VO2) did not change significantly, but the tendency was identical to that with hepatic perfusion. Hepatic clearance of thiopental as the product of hepatic extraction of thiopental (with a median value of 0.29) and hepatic plasma flow was 0.21 l/min. CONCLUSIONS. Thiopental is subject to a relatively low hepatic extraction of 0.29. Thus, changes in hepatic perfusion do not influence the elimination of thiopental. The actions of thiopental on global hemodynamics are comparable with the results found in the literature, characterized by a significant reduction in MAP and cardiac output after induction. The hepatic clearance of thiopental found in this study, with an absolute value of 0.21 l/min, is absolutely comparable with the data for total-body clearance reported in the literature. It is concluded that the liver is the only organ responsible for the elimination of thiopental in humans. PMID- 1590574 TI - [The use of propofol during diskectomy in neurosurgery]. AB - The intravenous anaesthetic agent propofol has become more and more popular not only for induction but also for the maintenance of anaesthesia in all fields of surgery. For this purpose, different infusion rates and also combinations of propofol with opioids, nitrous oxide and volatile anaesthetic agents have been described. The present study was designed to find the best dosage regimen for short operations and rapid changes. The necessity for the frequently recommended standardized combination of propofol with opioids should be checked with respect to the cardiovascular effects. METHODS. A series of 60 patients (ASA I and II, age range 22-79 years) selected for discectomy were prospectively randomized to three groups. Half an hour before operation all patient received 0.5 mg atropine, 50 mg promethazine and 50 mg pethidine as i.m. premedication. In all groups anaesthesia was induced with propofol in a bolus dose of 2.5 mg/kg body weight over a period of approximately 45 s. After 5 mg atracurium the patients were intubated under 100 mg succinylcholine and normoventilated with 70% nitrous oxide and 30% oxygen. For relaxation 25 mg of atracurium were given. In group I propofol was administered in a dosage of 15 mg/kg body weight per hour for 10 min after induction. After this time the propofol infusion was reduced to 6 mg/kg body weight per hour. Group II received 0.1 mg fentanyl before induction. The dosage of propofol was similar to group I. In group III 0.1 mg of fentanyl was administered before induction and propofol was given with an infusion rate of 6 mg/kg body weight from the beginning. The following parameters were controlled and documented: systolic and diastolic blood pressure (SAP and DAP), heart rate (HF), end-expiratory carbon dioxide (eeCO2), inspiratory oxygen concentration (FiO2) and peripheral oxygen saturation (sO2). Recovery time was determined as the time from the end of the propofol infusion until eye-opening on command. RESULTS. In all groups anaesthesia could be induced and maintained without complications. There was a slight increase in SAP in group I after intubation, while in the groups with fentanyl a pronounced decrease of SAP was found simultaneously with induction of anaesthesia (Fig. 1). In group I HF showed significantly higher values after intubation and for the next 15 min than in group II and group III. A rapid and pronounced increase of end-tidal carbon dioxide occurred in the fentanyl groups with the beginning of spontaneous ventilation at the end of anaesthesia. There was a significantly longer recovery time in group II with fentanyl and initial higher propofol infusion rate. A correlation between dosage of propofol and recovery time could not be found. DISCUSSION. The results of this study demonstrate that a routine combination of propofol with opioids is not necessary even for painful surgical procedures if the propofol dosage is initially increased. There are differences in cardiovascular reactions between group I without and groups II and III with fentanyl, but in our patients these changes were of no clinical importance. An additional administration of fentanyl can prevent hypertensive reactions or tachycardia with intubation, but on the other hand fentanyl can also increase the cardial depression of propofol with a dangerous decrease in blood pressure and heart rate. Therefore in combination with opioids lower doses of propofol should be used for induction and maintenance of anaesthesia. If opioids are administered, signs of a residual postoperative respiratory depression have to be taken seriously. PMID- 1590575 TI - [Cognitive and psychomotor performance following isoflurane, midazolam/alfentanil and propofol anesthesia. A comparative study]. AB - Mental and psychomotor abilities are impaired to varying degrees after general anaesthesia. This has important implications for the time over which patients are monitored in the recovery room and for the discharge of outpatients after day surgery. The present study was undertaken to compare recovery and mental and psychomotor skills in the first 60 min following general anaesthesia with isoflurane, midazolam/alfentanil and propofol. METHODS. A total of 45 patients undergoing microsurgical lumbar nucleotomy were randomized to three study groups. Group 1 (n = 15): anaesthesia was induced with thiopentone and maintained with isoflurane; group 2 (n = 15): anaesthesia was induced with midazolam and maintained with alfentanil; group 3 (n = 15): anaesthesia was induced and maintained with propofol. Vecuronium was used for muscle relaxation and the lungs were ventilated with a mixture of 66% nitrous oxide in oxygen. The following were checked 15, 30, 45, and 60 min after extubation: choice reaction times and critical flicker fusion for psychomotor testing; the maze test and a modification of the ball-bearing test for discrimination of motor and mental activities; and short- and long-term memory. RESULTS. Immediate recovery did not differ in the three different groups. In all patients psychomotor function was impaired compared with baseline for more than 60 min after general anaesthesia. However, impairment was significantly less pronounced after propofol, and recovery to preanaesthesia values was faster following propofol than after midazolam/alfentanil, and slowest after isoflurane-anaesthesia (Figs. 1, 2). The flicker fusion frequency, a very sensitive parameter for the persisting effects of anaesthetics, was significantly higher following propofol anaesthesia and remained so throughout the entire study period (Fig. 3). By 30 min after extubation, short-term memory was already normal in patients who had undergone propofol anaesthesia, and a statistically significant difference from the midazolam/alfentanil and isoflurane anaesthesia groups was obvious throughout the entire study period. However, no differences in long-term memory were found. At 30 min after propofol anaesthesia all patients were able to perform the ball bearing test, as against 13 patients following midazolam/alfentanil and 10 patients following isoflurane (Table 3). The maze test was mostly impaired after midazolam/alfentanil anaesthesia. Patients who underwent isoflurane anaesthesia needed the same time for the maze test at 60 min afterwards propofol patients needed after 30 min (Table 2). Side effects, e.g., nausea, vomiting, and double vision, were observed significantly more often in groups 1 and 2 (Table 4). DISCUSSION AND CONCLUSION. The results indicate that in operations of approximately 90 min duration the return of motor and mental abilities is faster following propofol anaesthesia. At 30 min after extubation following propofol anaesthesia patients had test results that allow their transfer from the recovery room, while it took 60 min for patients in the two other groups to reach the same levels of motor and mental function. This is important for the duration of monitoring in the recovery room and, especially, for day case anaesthesia. PMID- 1590576 TI - [Pneumothorax and cardiac arrest as complications of postoperative nasopharyngeal administration of oxygen]. AB - An unusual but life-threatening complication to nasopharyngeal oxygen administration is described. Following an unsuccessful attempt to advance nasogastric tube during anesthesia for cholecystectomy, the same nostril was used for an oxygen catheter at the end of operation. Within a few minutes after the oxygen supply had been opened following extubation, the patient developed submucous pharyngeal and mediastinal emphysema with subsequent bilateral pneumothorax and cardiac arrest. The patient was reintubated, received close chest cardiac compressions for a brief period, and the pneumothoraces were drained. She recovered completely within a few hours and was extubated uneventfully the following day. With the increasing--and justified--use of oxygen postoperatively in and during transport to the recovery room, this complication is likely to occur more often. In this case, the anesthetist's previous experience of this complication and consequent rapid therapeutic intervention was probably responsible for the favorable outcome. PMID- 1590577 TI - [Validation of the gas exchange monitoring function of the Engstrom Elvira respirator]. AB - Gas exchange monitoring (GEM) has only recently become available for routine use on ventilated patients. Engstrom has introduced a new concept of integrated gas exchange monitoring within the Elvira respirator, optionally combined with an external CO2 monitor. The following paper describes a laboratory validation of a prototype of this device with regard to the influence of respiratory variables within their specified ranges: FIO2 0.2-0.6, FIO2-FEO2 (DFO2) 0.02-0.05, FECO2 0.02-0.05, VI 5-20 l/min, p 10-60 mbar, respiratory rate 7-29, VT 500-2,000 ml, inspiratory flow 25-90 l/min, relative humidity 5% and 55%. VO2 and VCO2 (100-700 ml/min) were simulated by gas dilution at a respiratory quotient of 1 using a 'bag-in-the-bottle' test lung for 48 test situations. Two reference measurements per test situation were carried out by mass spectrometry and wet-gas spirometry. The Elvira GEM function uses a self-calibrating fuel cell for FO2 detection, an external infrared CO2 monitor (Eliza) for FECO2 measurement, and differential pressure detection on a venturi principle for inspiratory flow measurement. VI measurement necessitates the use of the Haldane transformation for VO2 and VCO2 calculation. The VO2 (VCO2) repeatability coefficient (2 s) for the reference method was 5.6 (5.5) ml/min compared to 10.3 (10.35) ml/min for the GEM function. The mean relative methodical difference for VO2 (VCO2) was +19% (+4.1%) with limits of agreement (+/- 2 s) of +/- 13% (+/- 8.7%). The systematical difference for VCO2 as well as the variability within different test situations was in an acceptable range for clinical measurement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590578 TI - [The modified Magill forceps]. AB - The Magill forceps are used for nasotracheal intubation, endotracheal suctioning, passing gastric tubes, placement of tampons in the nasopharynx and extraction of foreign material from the pharynx. There are several disadvantages of the standard Magill forceps; however: the danger of cuff perforation, the necessity of readjusting the forceps when placing a tube or catheter, and the risk of injury to the mucous membrane. For these reasons the standard Magill forceps have been modified: the jaws of the forceps have been changed to give curved atraumatic parts without any serrations or sharp edges. RESULTS. The resulting benefits are as follows: Reduced risk of injuring the mucous membrane and perforating the cuff. Tubes and catheter are safely guided between the semiround jaws, making it unnecessary to open the forceps repeatedly to advance the tube. Tampons being placed in the throat no longer get caught between the serrations, and even small foreign objects can easily be extracted from the pharynx. PMID- 1590579 TI - [A difficult intubation in a case of endolaryngeal paraganglioma]. AB - In a female patient aged 71, a tumor of unknown histology almost completely occupied the whole of the supraglottic space. Because of the valve-like behaviour of the tumor, the patient could not be ventilated by mask. Therefore, preoxygenation and preservation of spontaneous breathing were essential. Anaesthesia was induced by titration of etomidate, and no muscle relaxant or opioid was administered. The patient was successfully intubated by means of direct laryngoscopy. In all probability the blind nasal technique or the use of a fiberoptic device would not have been helpful, because the tumor had to be luxated before the endotracheal tube could be placed. Figure 1 shows the tumor (a) with a diameter of approximately 3 cm, which has displaced the epiglottis (b) to the left. A part of the endotracheal tube is visible at the bottom left. The spiral tube had to be replaced by a tube suitable for laser surgery. After resection (see Fig. 2) the coagulated tumor base (a) and the right vocal cord (b) can be seen with the laser tube still in place. Postoperatively extubation was possible. The histological examination revealed a paraganglioma without signs of malignancy. Apart from occlusion of the upper airway, the main danger stems from the considerable vascularization of such a paraganglioma. Not only the surgical procedure, but also minor manipulations during the endotracheal intubation may cause significant blood loss. In a small percentage of cases hormone-mediated cardiocirculatory complications may occur. If a difficult intubation is expected because of an endolaryngeal tumor, management should be based on the diagnostic findings and the planned surgical procedure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590580 TI - [The combined plunger pressure-manometer method. A technique for identifying the peridural space]. AB - The modified combined plunger pressure and manometer method (KSMM = Kombinierte Stempeldruck-Manometer-Methode) has proved to be a satisfactory alternative to the loss of resistance technique of Dogliotti. The method was tested for practicability and successful identification of the epidural space in 200 patients (80 of them pregnant) by physicians at different stages of their training. It makes it easy for young anaesthetists who are still in training and have not had much experience to learn to identify the epidural space. With this method the experienced operator can make an important contribution to the training of young doctors in epidural anaesthesia without fear of risks and failures. PMID- 1590581 TI - [Does an injection filter modify the cranial spread of a sensory blockade in epidural anesthesia?]. AB - In a prospective study we compared the spread of sensory blockade in epidural anaesthesia with and without Micropore filter. MATERIALS AND METHODS: A total of 32 patients undergoing varicose vein stripping under epidural anaesthesia were randomly assigned to two groups of 16 each. Bupivacaine 0.75% and POR 8 (0.1 IU/ml) were administered by means of a constant-velocity perfusor. In group A a Micropore filter was inserted between the perfusor syringe and the epidural catheter. In group B the epidural catheter was connected to the syringe without the filter. The puncture was performed at the L3-4 interspace with the patient in a sitting position. An epidural catheter was advanced 3 cm cephalad. Using the pin-prick method, the sensory level of the blockade was tested 5, 7, 10, 15, 20 and 30 min after injection of the local anesthetic solution. Statistical evaluation was performed with the t-test for unpaired samples. RESULTS. After 10 min the spread of analgesia was 5.75 +/- 1.26 segments in group A and 8 +/- 1.89 segments in group B; after 15 min it was 7.06 +/- 1.62 segments and 9.56 +/- 1.54 segments; after 20 min, 7.87 +/- 1.62 segments and 10.62 +/- 1.45 segments; and after 30 min 8.12 +/- 1.66 segments and 11.12 +/- 1.45 segments in group A and B, respectively. At any time sensory blockade was higher in group B (without Micropore filters) than in group A. The mean difference between the two groups amounted to 2-3 segments. The differences were significant at any time (P less than 0.001). These results show that the use of a Micropore filter in epidural anaesthesia leads to a reduced spread of sensory blockade. In our own examinations we found lowering of the pressure of the local anaesthetic solution that passes through the Micropore filter compared with the pressure of the solution injected without the filter. This seems to be the reason for the reduced spread of sensory blockade. Using these filters the onset of analgesia is delayed, and a given spread of analgesia needs a larger dose of local anaesthetic and is thus accompanied by a higher toxicity. PMID- 1590582 TI - [Micturition disorders following spinal anesthesia of different durations of action (lidocaine 2% versus bupivacaine 0.5%)]. AB - Disturbances of micturition following spinal anaesthesia are considered to be rare and harmless side effects of this technique. For this reason, we set up a prospective study to investigate their incidence, characteristics and intensity. Our special interest was directed at the influence of the duration of action of local anaesthetics. METHODS. In a randomized, double-blind study, two groups, each consisting of 73 trauma surgical and orthopaedic patients, received isobaric spinal anaesthesia with either lidocaine 2% or bupivacaine 0.5%. From the 1st to the 3rd postoperative day, the patients were interviewed daily and asked specifically about disturbances of micturition. RESULTS. The two groups were comparable in terms of clinical data, spinal anaesthesia and surgery. Disturbances of micturition occurred only during the first 24 h and were observed in a total of 42%. They were about twice as frequent after bupivacaine (56%) as following lidocaine (27%). After bupivacaine there was a higher rate of difficult micturition or complete inability to micturate in the presence of an urge to urinate, carbachol medication and catheterization of the urinary bladder. Sex and age had no influence on the incidence. A history of disturbances of micturition increased their frequency. DISCUSSION AND CONCLUSIONS. Disturbances of micturition are the most common side effect of spinal anaesthesia during the first 24 h after surgery. Their higher frequency following the longer acting bupivacaine may be evidence of longer lasting blockade of the efferent sacral parasympathetic fibers innervating the detrusor vesicae muscle, leading to inhibition of bladder voiding. The consequences of these disturbances, if not correctly managed, may be distension of the urinary bladder with ensuing infection and loss of tone of the detrusor muscle. Various measures are recommended: choice of the longer acting local anaesthetic only if necessary, careful control of bladder filling, restrictive infusion of fluids, early mobilization, carbachol, catheterization in good time, prophylactic placement of an indwelling catheter in patients with previous disturbances. PMID- 1590583 TI - Liquid chromatographic separation of alkanesulfonate and alkyl sulfate surfactants: effect of ionic strength. AB - The retention of alkanesulfonate and alkyl sulfate surfactants, which was determined on a reversed stationary phase as a function of mobile-phase ionic strength, is consistent with a double-layer type interaction at the stationary phase surface. Increasing the mobile-phase ionic strength not only increases retention but also improves resolution because peak widths are significantly reduced. The type of cation provided by the ionic strength salt also enhances retention, reduces peak width, and improves resolution. Lithium hydroxide is an ideal electrolyte for the separation of multicomponent mixtures of alkanesulfonate and alkyl sulfate surfactants. When the column effluent is passed through a postcolumn anion micromembrane suppressor, the conductivity due to the electrolyte is minimized and conductivity detection is sensitive, yielding a detection limit of about 0.3 nmol of injected analyte for a 3:1 signal:noise ratio. Multicomponent alkanesulfonate and alkyl sulfate mixtures from C2 to C18 are baseline resolved by using a mobile-phase gradient whereby CH3CN concentration increases and LiOH concentration decreases. PMID- 1590584 TI - L-alpha-glycerophosphate and L-lactate electrodes based on the electrochemical "wiring" of oxidases. AB - The title electrodes were constructed by coimmobilizing the respective FAD oxidases on solid electrode surfaces with a poly(vinyl pyridine) polymer which was N-derivatized with bromoethylamine and Os(bpy)2Cl2. The redox-polymer-enzyme hydrogels were cross-linked on the electrode surface using poly(ethylene glycol) diglycidyl ether. As in the case of glucose oxidase, the redox polymer acts as an electron relaying "wire" transferring electrons directly from the enzymes' FADH2 centers to the electrode. This transfer competes with the natural process of reoxidation of FADH2 by molecular oxygen. The variation of the response of these electrodes with the atmosphere (N2 or air), pH, and substrate concentration was determined. The pH profile of the electrocatalytic current differs from that of the activity of the free enzymes, exhibiting a broader maximum, shifted to higher pH values. The observed sensitivities and linear ranges are respectively 2 x 10( 2) A M-1 cm-2 and 2.7 mM for L-alpha-glycerophosphate, and 0.3 A M-1 cm-2 and 0.2 mM for L-lactate that may be compared to 2 x 10(-2) A M-1 cm-2 and 10 mM for glucose. The 0-90% response time for all electrodes is 1 s or less. PMID- 1590585 TI - Determining volatile organic compounds in human blood from a large sample population by using purge and trap gas chromatography/mass spectrometry. AB - Volatile organic compounds (VOCs) are a major public health concern, because of their ubiquitous nature and the possible health effects associated with exposure to them. An analytical method has been developed that enabled the determination of parts per trillion levels of 32 VOCs in 10 mL of blood. Special efforts toward reducing blank levels and improving measurement sensitivity have resulted in an analytical method that shows excellent reproducibility and recovery even at these ultratrace levels. Results on normal human blood indicate that quantifiable levels of eleven VOCs can be found in virtually all whole blood samples. In a fraction of the samples, six other VOCs can also be determined at levels above detection limits. This method shows promise as a technique for estimating the normal baseline level of VOCs in human blood and may have future applications in cases of exposure. PMID- 1590587 TI - Substrate-assisted laser desorption of neutral peptide molecules. AB - The ultraviolet (248-nm) laser desorption of neutral peptide molecules is found to be greatly enhanced by applying a thin layer of the sample (500 monolayers) on top of an ultraviolet-absorbing organic substrate, sinapinic acid. With this sample preparation, peptides as large as gramicidin S are desorbed as intact neutral molecules. The samples are examined with laser desorption/chemical ionization (LD/CI) Fourier transform mass spectrometry. The neutrals desorbed by this method have approximately 1 eV less internal energy than those desorbed directly from a metal film surface. The organic substrate aids the desorption of neutrals when the laser wavelength is not strongly absorbed by the peptide sample (248 nm), but is not effective in aiding the desorption of neutrals when the laser wavelength is strongly absorbed by the sample (193 nm). PMID- 1590586 TI - Characterization of dibromopolychlorodibenzo-p-dioxins and dibromopolychlorodibenzofurans in municipal waste incinerator fly ash using gas chromatography/mass spectrometry. AB - Several fly ash samples from different countries were analyzed for dibromopolychlorodibenzo-p-dioxins and -dibenzofurans (DBPCDD/Fs) using capillary column gas chromatography/high-resolution mass spectrometry. Concentrations of these compounds ranged from low to high parts-per-trillion (pptr) depending on the location where the samples were collected. The mass spectrometer, operated at greater than 10,000 mass resolution in combination with the high resolving power of capillary column GC, permitted characterization of DBPCDD/Fs in municipal waste incinerator fly ash for the first time. The isomer patterns of tetra- through octa-congener groups of DBPCDD/Fs are remarkably similar regardless of where the fly ash originated, indicating common mechanisms of formation of these compounds in the incinerators. PMID- 1590588 TI - Principal component analysis, trace elements, and blue crab shell disease. PMID- 1590589 TI - Mechanistic studies of electrostatic potentials on antigen--antibody complexes for bioanalyses. AB - A concept involving the use of antibodies conjugated with reporter molecules for the direct sensing on the subtle changes in the local electrostatic environment of antigen-antibody complexes due to the antigen binding was proposed and demonstrated. The studies including the effect of solution conditions on the extent and magnitude of the electrostatic potentials around the antigen-antibody complex and the quantitative dependence of the distance between the reporter molecule and the antigen-antibody binding site on the effectiveness of the reporter molecule for sensing the antigen-antibody binding event are presented and discussed. Basic understanding of induced changes in the electrostatic potentials on the antigen-antibody complex is essential for implementing the proposed direct sensing mechanism. PMID- 1590590 TI - Supercritical fluid extraction of active components in a drug formulation. AB - Sulfamethoxazole and trimethoprim have been extracted from a drug formulation, Septra Infusion, with pure supercritical carbon dioxide. Both direct extraction of the aqueous-based matrix and indirect extraction of the formulation immobilized onto Celite were studied. Exhaustive analytical extraction was achieved when active components were less than 1.0 mg. A number of co-extractants were found, but each was blind to the HPLC/UV assay. PMID- 1590591 TI - Incidence of phthirapteran infestation upon the buffaloes of Dehradun (India). AB - Out of 373 buffaloes examined in different localities of Dehradun, 60.58% have been found infested with Haematopinus tuberculatus. Incidence of infestation was higher on adults than on youngs. The lice index was highest in January and lowest in June. The adults and nymphs preferred neck, back, ribs, shoulder, belly, thigh, hind, flank, head, hind legs, tail, fore legs and fore flank in this order of decreasing frequency. On the other hand eggs were found most heavily concentrated on neck and back regions. PMID- 1590592 TI - [The epidemiology of Taenia saginata taeniasis]. AB - The aim of the epidemiological analysis was to detect the distribution and changes in the incidence of Taenia saginata and to find the relations between taeniosis and cysticercosis in the district of Halle (Saale). The morbidity rate of taeniosis was calculated at first by the number of notified cases and also by the quantity of anthelmintics in the treatment of T. saginata infections in humans. The morbidity based on notifications did not show any relations to the frequency of metacestodes of T. saginata in cattle. This morbidity rate gave an exact relation to the number of notified cases but not to the number of real cases of cestodes in humans. On the contrary, the theoretical morbidity based on used anthelmintics developed parallel to the degree of infestation in cattle. Therefore this theoretical morbidity is very suitable for epidemiological studies of taeniosis. PMID- 1590593 TI - The male reproductive organs in the chronic phase of experimental Chagas' disease. AB - A previous study showed amastigote forms of Trypanosoma cruzi in the sex organs of male mice 15 days after inoculation. The purpose of the present work was to investigate the sequelae occurring in the male reproductive system during a later phase of Chagas' disease. Depleted germinal epithelium and release of immature germ cells into the tubular lumen were observed in the testis of chronic chagasic mice. The relative weights of the epididymis, vas deferens and seminal vesicle were significantly increased. Histological examination revealed a sharp thinning of the ductal and acinar walls. The results are discussed in terms of a neuromotor disturbance leading to sperm retention. PMID- 1590594 TI - Comparative study of soluble protein profiles of different Trichinella isolates. AB - The comparison and characterization of different populations of Trichinella has become possible through the study of their complex polypeptide profiles. Techniques such as polyacrylamide gel electrophoresis (SDS-PAGE) and isoelectric focusing (IEF) provide a high capacity of resolution. We used both techniques to compare proteinograms of different Trichinella isolates, in order to characterize an isolate detected in a wild boar captured in Guejar-Sierra (Province of Granada, Spain). PMID- 1590595 TI - Glycogen, protein and lipid content of adult Fasciola gigantica (Trematoda). AB - The concentration of carbohydrates, proteins, and lipids in the whole worm, gut, and body musculature of Fasciola gigantica was investigated from worms collected from cattle slaughtered in the Jos abattoir. Protein accounted for the highest concentration of the constituents constituting 62.59 +/- 0.86% of the dry weight of the fluke. This was followed by lipid with 28.15 +/- 0.86% of the dry weight while carbohydrate (glycogen) was 6.29 +/- 0.11% of the dry weight. Thin-layer chromatography revealed the presence of six distinct bands of neutral lipids, namely: monoglycerides, 1,2-diglycerides, 1,3-diglycerides, free fatty acids, triglycerides and sterol esters from both whole worm homogenate and fractions of the gut and muscle tissues. In the case of phospholipids, lysophosphatidyl choline, sphingomyeline, phosphatidyl choline and phosphatidyl-ethanol amine were recovered. When the free fatty acids were subjected to further fractionation, palmitic, stearic, as well as oleic acids were recovered in appreciable quantities indicating that lipids are being catabolized in these trematodes. PMID- 1590596 TI - Mixed infestation of a domestic cat by Aelurostrongylus abstrusus and Oslerus rostratus. AB - Two types of nematodes were found in the lungs of a Spanish cat in poor condition. One type was identified as the rather common Aelurostrongylus abstrusus. The other, although presenting slight differences in some of its measurements, had the morphologic features and the characteristic location of Oslerus rostratus, a species which apparently has not been previously reported in Europe. It is hypothesized that O. rostratus is a parasite of wild felids, the domestic cat being just an accidental host. No severe pathological changes were related to the presence of O. rostratus. PMID- 1590597 TI - [The modification of Helicella obvia by Dicrocoelium parthenitae]. AB - During the pasture period in 1990 the snail species Helicella obvia, collected in a dicrocoeliosis area in the east of Brandenburg, was investigated for Dicrocoelium sporocysts. Simultaneously in adult snails the condition of albumen gland was examined. Investigations showed that Dicrocoelium infection in the snail host impairs their reproduction ability and life expectancy. The term "parasite caused sterilisation" is suggested for changes which lead to infertility in the case of parasite infection. PMID- 1590598 TI - [The life of a parasitologist]. PMID- 1590600 TI - A multicenter questionnaire investigation of attitudes toward hand hygiene, assessed by the staff in fifteen hospitals in Denmark and Norway. AB - A questionnaire survey was carried out anonymously among 2557 health care workers in Denmark and Norway to identify and quantify factors that affect the handwashing behavior of physicians, nurses, and other staff groups who perform direct patient care. For number of daily patient contacts physicians reported significantly fewer instances of hand hygiene (HH) per day than did those in other medical professions. Male physicians reported significantly fewer HH per day than did their female colleagues. Significant differences were found among staff groups in emphasis on factors motivating and discouraging HH. The main motivating factor for all groups, however, was an awareness that HH is important for the prevention of infection. Skin problems from frequent handwashing and the use of agents that irritate and dry the skin were the main reasons for disinclination toward HH. The number of points given to these statements correlated well with the stated frequency of HH in staff groups with relatively many (9 to 24) patient contacts per day. Many studies have revealed low standards of HH in health care settings. Whenever HH is taught, the significance of HH for the prevention of infection is always stressed. The participants in this survey were well aware of this significance, but there is still a discrepancy between theory and practice. Goal-specific strategies to improve HH practices would probably be more effective if more were done to minimize the factors that health care workers find detrimental to HH. Continual evaluation of the possibly detrimental effects of current hand washing agents should also be carried out. PMID- 1590599 TI - Exposure to blood during various procedures: results of two surveys before and after the implementation of universal precautions. AB - In an attempt to define better situations involving exposure to blood, we surveyed nurses (N = 565) in a 1000-bed university hospital to determine the following for the last working shift: the rate of cutaneous exposure to blood for different procedures, the rate of needlestick injury, and the prevalence of hand lesions. Among nurses who had performed at least one of the specified procedures, 42% had been exposed to blood with unprotected skin. Direct examination of 100 pairs of hands revealed that 57% of the nurses had either acute or chronic skin lesions. Universal precautions were introduced, and a similar survey (N = 541) was carried out 1 year later to assess compliance. Exposure of unprotected skin to blood had been reduced to 27%, although 46% of nurses had not used gloves for any of the procedures they had performed. The main reason given by nurses for not wearing gloves was that they did not consider the patient to be at risk for carrying a blood-borne infection. The rate of needlestick injuries was high and had remained stable at approximately 2.8 needlesticks/nurse per year, as determined by information from the last working shifts. We conclude that compliance of nursing personnel with universal precautions was insufficient, despite an informational campaign throughout the hospital. Repeated instruction on barrier precautions and the prevention of needlestick injury (including the correct use of disposable containers) is necessary to ensure optimal protection. PMID- 1590602 TI - Impact of a needleless intravenous system in a university hospital. PMID- 1590601 TI - Handwashing practices and resistance and density of bacterial hand flora on two pediatric units in Lima, Peru. AB - The handwashing practices and bacterial hand flora of 62 pediatric staff members of a teaching hospital in Lima, Peru, were studied. Handwashing followed patient contact 29.3% of the time (204/697 contacts). Mean duration was 14.5 seconds, and significant differences in practices were found by unit (rehydration or neonatal intensive care), type of staff member (nurses or physicians), and type and duration of patient contact. Mean count of colony-forming units was log10 5.87 +/ 0.41, with significant differences in density of flora found between patient care and kitchen staffs. There was no significant effect of handwashing on counts of colony-forming units. Significant differences were also found by unit and by staff position with regard to species isolated and antimicrobial resistance of isolates. A more efficacious and cost-effective form of hand hygiene and a more prudent use of antimicrobial agents are indicated. PMID- 1590603 TI - The problem of methicillin-resistant Staphylococcus aureus: a critical appraisal of the efficacy of infection control procedures with a suggested approach for infection control programs. PMID- 1590604 TI - Neuromuscular blockade in aeromedical airway management. AB - STUDY OBJECTIVE: Induction of paralysis before intubation is controversial in the aeromedical setting. We reviewed our experience using neuromuscular blockade with nurse/paramedic aeromedical teams to determine effectiveness and outcome. MATERIALS AND METHODS: In 670 flights during a 16-month period, 119 patients required endotracheal intubation aided by muscle relaxant administration. Age ranged from two months to 83 years, with a mean of 33 years. All patients were hyperventilated with 100% oxygen before intubation. Sedation was given if presenting systolic blood pressure was greater than 100 mm Hg. A short-acting depolarizing agent was then given in a 1-mg/kg dose. Once the airway was secure, a longer-acting, nondepolarizing agent and/or sedation was given. RESULTS: Of the 119 patients, 115 (96.6%) were orally intubated. Four (3.4%) required surgical airway intervention because of injuries and conditions prohibiting oral intubation. Of 115 oral intubations, 99 (86%) were achieved on the first attempt. Eight patients (7%) were intubated on a second attempt, and another eight were intubated on a third attempt. There was no change in operator. Sixty-eight percent of patients requiring airway management were multiple trauma victims with associated head injuries. There were no laryngeal injuries, detected cardiac rhythm changes, bleeding episodes, or neurologic complications despite incomplete cervical-spine evaluation. CONCLUSION: Neuromuscular blockade can be used safely and effectively in the field by experienced nurse/paramedic teams. Although problematic intubation was not eliminated, the difficulties encountered were manageable and the overall risk/benefit ratio was acceptable. PMID- 1590605 TI - Effects of prehospital medications on mortality and length of stay in congestive heart failure. AB - HYPOTHESIS: Prehospital medications for congestive heart failure should affect hospital outcomes (survival and length of stay). STUDY DESIGN: In a retrospective case series, hospital outcomes were compared for patients treated with prehospital nitroglycerin, furosemide, and/or morphine (252) versus those given no medications (241). SETTING: A rural/suburban emergency medical services system (population 140,000) served by three paramedic units. PARTICIPANTS: Four hundred ninety-three consecutive cases of congestive heart failure or pulmonary edema were identified by hospital discharge diagnosis from a data base of 8,315 paramedic transports with known outcome. INTERVENTIONS: Oxygen was given by protocol to 489 patients. Other medications were given by order of on-line physician medical command. RESULTS: Overall mortality was 10.9% (54 of 493). Treated and untreated patients were comparable in age, sex, cardiac rhythms, prior use of cardiac medications, and response and scene times; mortality was reduced in treated versus untreated patients (odds ratio for improved survival, 2.51; 95% confidence interval, 1.37 to 4.55; P less than .01). Positive treatment effect was greatest for 58 nonhypotensive, critical patients (odds ratio for survival, 10.25; P less than .01). No single drug combination was unique in terms of treatment benefit. Patients treated in the field received medications 36 minutes earlier than patients first treated in the emergency department. No survival benefit was evidence for noncritical, nonhypotensive patients, and patients with final diagnoses of asthma, chronic obstructive pulmonary disease, pneumonia, or bronchitis had a higher than expected mortality if erroneously treated for congestive heart failure. Differences in hospital length of stay were not significant for any group. CONCLUSION: Prehospital medications improve survival in congestive heart failure, especially in critical patients. More than one combination of medications seems effective, and early treatment is associated with improved survival. However, these medications appear to increase mortality in patients misdiagnosed in the field. Factors used in paramedica and medical command assessments require further study. PMID- 1590606 TI - Prehospital pulse oximetry: useful or misused? AB - STUDY OBJECTIVE: This study evaluated the ability of emergency medical technicians (EMT-As) and emergency medical technicians-paramedics (EMT-Ps) to use pulse oximetry measurements in determining patient oxygen requirements. DESIGN: Prospective case series. SETTING: Cleveland emergency medical services (EMS) system. TYPE OF PARTICIPANTS: Five hundred thirty-two consecutive patients transported to Cleveland area hospitals by the Cleveland EMS system; no exclusions. INTERVENTIONS: EMT-Ps and EMT-As predicted patients' supplemental oxygen requirements based on clinical assessment. Pulse oximetry was performed while patients were breathing room air (RA SpO2). Treatment intervention, including oxygen supplementation and medication given, oxygen saturation after intervention, and oxygen saturation on arrival at the hospital, was also recorded. Therapy guided by the patient's initial RA SpO2 was reviewed to determine the appropriateness of oxygen therapy. RESULTS: Data were analyzed using the chi 2 test and correlation analysis. Eleven percent (59) of patients transported by Cleveland EMS had an initial RA SpO2 of less than 91%. Advanced life support units increased oxygen supplementation on all desaturated patients, whereas basic life support units failed to make appropriate increases in FIO2 in 20% (two) of desaturated patients (P less than .0001). Sixty percent (164) of patients transported by EMT-Ps and 62% (162) of patients transported by EMT-As had an initial RA SpO2 of 97% or greater. EMT-Ps gave supplemental oxygen therapy to all but 7% (11) of these already well-saturated patients, and EMT-As gave supplemental oxygen to all but 6% (nine) of these patients. EMT-Ps administered a higher FIO2 than they had predicted clinically necessary to 2% (four) of patients with an initial RA SpO2 of 97% of greater, whereas EMT-As gave a higher FIO2 than initially predicted to 16% (25) of such patients (P less than .0001). CONCLUSION: EMT-Ps were more likely to appropriately base oxygen therapy on oximetry measurements than were EMT-As. Both groups failed to decrease supplemental oxygen in patients with high explicit protocols for EMS systems contemplating the use of oximetry to guide oxygen therapy. Our results further suggest that pulse oximetry could be used to avoid unnecessary oxygen therapy on a significant number of patients transported by EMS systems because they are already well saturated on room air. PMID- 1590607 TI - Trauma triage: a nine-year experience. AB - STUDY OBJECTIVE: To describe the Orange County trauma system's nine-year (July 1980 through June 1989) experience with patient triage. Changes in patterns were sought after the 1983 revisions in triage criteria. DESIGN: A nine-year retrospective analysis of trends in trauma patient triage in Orange County. A pre analysis and postanalysis to discern changes in trends after a July 1983 revision in triage criteria was conducted. SETTING: Orange County, California, Emergency Medical Services (EMS) Agency, serving an urban population of more than 2 million. Orange County EMS responds to about 90,000 calls annually, 3,500 of which are for trauma patients. Twenty-eight nontrauma and neurosurgical paramedic receiving centers and four paramedic trauma receiving centers served the community during the study period. TYPE OF PARTICIPANTS: All patients triaged to Orange County trauma centers between July 1980 and June 1989. Single neurologic injury patients were triaged to neurosurgical receiving centers and are not included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Logarithmic regression analysis showed a 386% increase in the number of trauma patients triaged to trauma centers. The number of more seriously injured patients, as estimated by length of hospital stay of more than four days; Injury Severity Score of more than 15; fatality; or patients requiring surgery within six hours for trauma to the chest, abdomen, central nervous system, and/or major vessel, also increased. The rates of increase were more than those of the population (15%) for the Injury Severity Score of more than 15 group (79%) and the length of stay of more than four days group (108%), but lower for the fatality group (11%) and the early surgery group (7%). Because traffic and motor vehicle accidents comprise 70% to 80% of all trauma injuries, a separate analysis was conducted for these cases, using numbers of miles traveled as a basis for analysis. The analysis revealed a significant (alpha = .05) increase in over-triage rate, from 43% in 1981 to 74% in 1988, for motor vehicle accident patients. No changes in trends were found in the pre-analysis and postanalysis. Changes in trends occurred in 1986. CONCLUSION: The growth rate for the total trauma population exceeds that for overall county population growth. These results suggest overtriage. No changes in trends were found after the 1983 revisions in triage criteria. Changes in trends were found in 1986 after the revisions in the Injury Severity Score scoring system. PMID- 1590608 TI - Using paramedics to identify at-risk elderly. AB - OBJECTIVES: To evaluate paramedics' ability to identify elderly at risk and refer them for assessment and service. DESIGN: A prospective nonrandomized open trial. SETTING: Akron, Ohio, a midsize city with a well-developed advanced life support emergency medical services system. TYPE OF PARTICIPANTS: One hundred thirty firefighter paramedics evaluated 6,000 elderly patients. Assessments were performed by trained geriatric assessors. INTERVENTION: Regardless of the reason for the call, paramedics screened all emergency medical services users age 60 and older for medical, mental health, social, and environmental problems. Identified cases were referred to the Area Agency on Aging for assessment and follow-up. MAIN RESULTS: Paramedics identified 197 people with possible problems, 124 of whom received an assessment. The remainder could not be assessed due to death, moving, referral, or transfer to a long-term care facility. Assessors confirmed the presence of a problem in 121 of 124 assessed cases, a positive predictive value of 98%. The program was useful for 94 people, 48% of those identified and assessed. CONCLUSION: Paramedics can serve as case finders for at-risk elderly, and effective linkage to service agencies can occur. PMID- 1590609 TI - Automated external defibrillators: implications for training qualified ambulance staff. AB - STUDY OBJECTIVE: To investigate the performance of basic trained ambulance personnel using an automated external defibrillator (AED) after a short training program. METHODS: One hundred ninety ambulance attendants working in London received six and one-half hours training in the use of an AED, with written feedback and continuing education regarding performance after training. Performance was assessed over a period of 15 months by analysis of report forms and ECG/audible cassette tapes from the patients who were treated. RESULTS: Staff were able to operate the defibrillator correctly in 96% of cases and followed the protocol sequence taught in 34% of cases. The median time taken to activate the defibrillator following arrival of the ambulance at the scene of cardiac arrest was four minutes (range, one to 13 minutes). In 32% of cases, patients were intubated erroneously or moved to the ambulance before the AED was attached. CONCLUSION: The short course with continuing education was sufficient to train staff in AED operation, but errors in protocol compliance occurred throughout the trial. PMID- 1590610 TI - Community trends in CPR training and use: the Minnesota Heart Survey. AB - STUDY OBJECTIVE: To examine community changes in self-reported CPR training and use from 1980-82 to 1985-87 using data obtained from the Minnesota Heart Survey. A comparative investigation of CPR training among blacks and whites in 1985-86 also was completed. DESIGN: Data were obtained in 1980-81, 1981-82, 1985-86, and 1986-87 from four population-based samples drawn from the seven-county Minneapolis-St Paul metropolitan area. To increase sample sizes and to compare prevalences of CPR training and use in the early 1980s with prevalences in the mid-1980s, the four Minnesota Heart Survey surveys were combined into two time periods, 1980-82 and 1985-87. A separate survey of black individuals was conducted in 1985, and these data were used in the comparisons between blacks and whites in 1985-86. RESULTS: The prevalence of whites trained in CPR increased significantly between 1980-82 and 1985-87 in both nonhealth professionals (18.5% vs 30.9%) and health professionals (71.9% vs 86.8%). No significant change was observed between the two periods in the percentage of nonhealth professionals who had ever used their CPR skills (9.7% vs 10.7%), whereas use among health professionals increased significantly (40.2% vs 53.4%). Training within the prior two or three years decreased from 1980-82 to 1985-87 among nonhealth professionals, but increases in recent training were observed among health professionals. There were no significant differences between black and white nonhealth professionals in the prevalence of CPR training. Black trainees, however, reported a higher percentage of ever using CPR skills than white trainees (15.4% vs 9.8%, respectively). Black trainees also had higher rates of recent CPR training than white trainees. No differences were observed between black and white health professionals regarding CPR training and use, or recency of certification. CONCLUSION: These results suggest that the percentage of individuals trained in CPR is increasing. Improvement is needed, however, in the rates of recent certification among nonhealth professionals. PMID- 1590611 TI - Effects of alcohol intoxication on the initial assessment of trauma patients. AB - STUDY OBJECTIVES: To evaluate the influence of alcohol intoxication on the initial assessment and treatment of trauma patients. DESIGN: A prospective study of 2,237 trauma patients 18 years of age or older admitted to a Level I trauma center over a 19-month period. RESULTS: The study population was primarily male (78%) and white (73%) and had sustained blunt trauma (79%). One thousand fifty three patients (47.1%) had positive blood alcohol concentration (BAC); median BAC in patients with any detectable alcohol was 179 mg/dL. When stratified by injury severity categories and compared with nonintoxicated (BAC less than 100 mg/dL) patients, intoxicated patients with an Injury Severity Score (ISS) of 1 to 15 were more likely to undergo the following: field and/or ED intubation (relative risk [RR], 2.22; 95% confidence interval [CI], 1.7 to 2.7); diagnostic peritoneal lavage (RR, 1.83; CI, 1.43 to 2.3); head computed tomography scanning (RR, 1.18; CI, 1.0 to 1.4); and intracranial pressure monitoring (RR, 1.41; CI, 0.74 to 2.7). The effects were less pronounced for those patients with an ISS of more than 15, except for intracranial pressure monitoring where patients with an ISS of more than 15 were 47% more likely to have intracranial pressure monitoring if intoxicated (RR, 1.47; CI, 1.2 to 1.9). CONCLUSION: Acute intoxication appears to alter the initial assessment of injury severity, resulting in an increased use of invasive diagnostic and therapeutic procedures. PMID- 1590612 TI - Emergency department echocardiography improves outcome in penetrating cardiac injury. AB - STUDY OBJECTIVES: To determine the effect of immediate two-dimensional echocardiography on the time to diagnosis, survival rate, and neurologic outcome of patients with penetrating cardiac injury. DESIGN: A ten-year retrospective review. SETTING: Regional trauma center serving a population base of 1.25 million with 85,000 visits yearly. TYPE OF PARTICIPANTS: All patients presenting to the emergency department with penetrating cardiac injury. MEASUREMENTS AND MAIN RESULTS: The records of 49 patients with penetrating cardiac injury were reviewed. Of these, 28 received immediate two-dimensional echocardiography in the ED (echo group) and 21 did not (nonecho group). The probability of survival was derived using TRISS methodology. Differences between groups were determined using either the two sample t-test for parametric data or the Mann-Whitney test for nonparametric data. The overall probability of survival was 33.2%, and the actual survival rate was 81.6%. The probability of survival was 34.2% and 31.8% for the echo group and nonecho group, respectively. The actual survival was 100% in the echo group and 57.1% in the nonecho group. The average time to diagnosis and disposition for surgical intervention was 15.5 +/- 11.4 minutes for the echo group and 42.4 +/- 21.7 minutes for the nonecho group (P less than .001). The Glasgow Outcome Score was 5.0 for the echo group and 4.2 for the nonecho group (P = .007). CONCLUSION: Since the introduction of immediate ED two-dimensional echocardiography, the time to diagnosis of penetrating cardiac injury has decreased and both the survival rate and neurologic outcome of survivors has improved. PMID- 1590613 TI - Evaluation of the tilt test in an adult emergency medicine population. AB - STUDY OBJECTIVE: To evaluate the usefulness of the tilt test in identifying significantly dehydrated or occultly bleeding adult patients in an emergency department. DESIGN: Prospective. SETTING: Urban ED. TYPES OF PARTICIPANTS: Two hundred two ill adult patients with complaints suggestive of dehydration and/or occult blood loss and a control sample of 21 healthy individuals. INTERVENTION: Orthostatic measurements were taken from blood samples from the ill and healthy patients. The estimates of the degree of dehydration measured or calculated were total body water deficit percentage (based on measured serum osmolality), ratio of blood urea nitrogen to creatinine, creatinine, and hematocrit. Multiple historical and physical examination variables related to dehydration or occult bleeding were recorded. MEASUREMENTS AND MAIN RESULTS: Multiple analysis of variance testing of the historical and examination variables in the 166 dehydrated patients revealed the absence of syncope (P = .037) and the lack of axillary sweat (P = .026) to be significantly associated with an increased level of dehydration. Regression analysis of the orthostatic measurements and age with the estimates of dehydration found that orthostatic change in heart rate (P = .0165) and age (P = .0047) demonstrated a very small (r2 = .098) association with the level of dehydration. Orthostatic changes in systolic blood pressure and diastolic blood pressure demonstrated no statistically significant association with level of dehydration. There was wide variation in the tilt test measurements in samples from both the healthy and the ill patients: heart rate, 6.8 +/- 7.8 versus 13.2 +/- 10.5; systolic blood pressure, -2.5 +/- 8.0 versus -8.3 +/- 12.8 mm Hg; and diastolic blood pressure, 5.3 +/- 9.9 versus 0.6 +/- 8.6 mm Hg, respectively. The only parameter that attained statistical significance between the 36 blood-loss patients and the healthy patients was change in systolic blood pressure (P = .001); however, this was not clinically significant (-10.7 +/- 13.7 versus -2.5 +/- 8.0 mm Hg, respectively). CONCLUSION: It appears impossible to define a "positive" tilt test that would adequately identify patients with clinically significant dehydration or blood loss; this is due to the large variance in patients' orthostatic measurements both in a healthy and in an ill state and the lack of a significant correlation of orthostatic measurements to a level of dehydration. Lack of axillary sweat, no complaint of syncope, and younger age all indicate greater degrees of dehydration. PMID- 1590614 TI - Head, facial, and clavicular trauma as a predictor of cervical-spine injury. AB - STUDY HYPOTHESIS: The American College of Surgeons teaches that "trauma occurring above the clavicle should raise a high suspicion for a potential cervical spine injury." In this study, we investigated the association of head, facial, and clavicular trauma with cervical-spine and cord injury. METHODS: The records of 5,021 consecutive trauma patients admitted to a level I regional trauma center during a three and one-half year period were reviewed retrospectively. The incidence rates of head, facial, clavicle, cervical spine, and cervical cord injuries were recorded. Glasgow Coma Scores (GCS) were obtained on all patients. Statistical analysis using multiple logistic regression and chi 2 analysis were performed to determine the relationship between traumatic injury above the clavicle and cervical spine and cord injury. RESULTS: Head-injured patients had no greater incidence of cervical-spine injury than did non-head-injured patients (4.76% vs 4.37%, P = .52) but were found to have significantly fewer spinal cord injuries (1.5% vs 2.3%, P = .048). There was no difference in incidence of cervical-spine injuries between patients with and those without facial injuries (4.2% vs 4.6%, P = .61). However, there were significantly fewer cord injuries among patients with facial injuries (0.75% vs 2.2%, P = .01). The presence or absence of clavicular fracture was not associated with a significant increase in cervical spine (6.9% vs 4.4%, P = 11) or cervical cord injuries (1.6% vs 2.0%, P = .68). A GCS of less than 14 was associated with a higher incidence of cervical spine injury than was a GCS of 14 or more in both head-injured (6.7% vs 3.9%, P = .007) and non-head-injured patients (12.2% vs 5.9%, P = .002). There was a greater incidence of cervical cord injury among patients with a GCS of less than 14 than in those with a GCS of 14 or more in both the head-injured (2.2% vs 1.2%, P = .09) and non-head-injured (8.8% vs 2.7%, P less than .0001) groups. CONCLUSION: Trauma to the head, face, and clavicle is not associated with a higher incidence of cervical-spine or cord injury. Physiologic parameters such as the GCS appear to be more accurate predictors of cervical spine or cord injury than mere evidence of trauma occurring above the clavicle. PMID- 1590615 TI - Effect of body locale and addition of epinephrine on the duration of action of a local anesthetic agent. AB - STUDY OBJECTIVE: Little information exists relating body locale to the duration of action of local anesthetics. We tested the duration of action of a local anesthetic with and without epinephrine at different body locales. PARTICIPANTS: Twenty healthy volunteers aged 27 to 48 years (mean, 32.0 years). INTERVENTIONS: In the first of two experiments (L), 20 subjects had 1 mL buffered 1% lidocaine injected intradermally on the forehead, hand, forearm, and calf. In the second experiment (LE), ten subjects were injected at the same sites with lidocaine containing epinephrine. METHODS: Subjects ranked anesthesia by reaction to pinprick from 0 (complete) to 20 (none) on a scale with testing done every 15 (L) or 30 (LE) minutes and continued until no anesthetic effect was present. Duration of effective and of any anesthesia were times until score of more than 5 and of more than 19, respectively. Mean duration of anesthesia was compared by analysis of variance (between body areas) and paired two-tailed t-test (L vs LE). Significance was taken as P less than or equal to .05. RESULTS: Anesthesia was significantly briefer for the face than for all other body locales by both indexes of duration and for both plain lidocaine and lidocaine with epinephrine (P less than .001 to P less than .05). Anesthesia with epinephrine lasted significantly longer than with lidocaine alone at all body locales and for duration of both effective or any anesthesia (P = .0001 to P = .001). Based on 95% confidence interval limits, the duration of anesthesia at other body locales is predicted to be 1.3- to 3.2-fold that on the face. Confidence interval analysis indicated that addition of epinephrine to lidocaine increases the duration of anesthetic action by 1.3- to 13.0-fold that of lidocaine alone. CONCLUSION: The duration of action of local anesthesia is considerably shorter for the face than for other body areas. Epinephrine significantly increases the duration of action of lidocaine at all body locales. PMID- 1590616 TI - Female sexual assault: medical and legal implications. AB - STUDY OBJECTIVE: To assess the medical and legal effectiveness of this institution's existing adult female sexual assault protocol. DESIGN: Retrospective review. SETTING: Urban public hospital. TYPE OF PARTICIPANTS: One hundred eighty-two adult female sexual assault victims undergoing evaluation within 36 hours of assault. MEASUREMENTS AND MAIN RESULTS: Each case was reviewed with specific attention to associated injuries, sexually transmitted disease, compliance with medical follow-up, pregnancy, and legal outcome. Half of all cases had associated injuries. Nine percent of the women were found to have genital trauma on pelvic examination, although only 29% of these women had complaints of genital pain or bleeding. Ten percent of all women had positive gonorrhea cultures at initial examination. Thirty percent of the women completed the follow-up protocol. None of the women given postcoital estrogen therapy is known to have become pregnant. Only 53 of the 182 cases had the potential for successful prosecution with both a victim willing to cooperate in prosecution and an identified assailant. Thirty-four percent of these cases resulted in a successful prosecution. Evidence of genital or nongenital trauma was significantly associated with a successful legal outcome. CONCLUSION: A physical and evidentiary examination, including pelvic examination and assays for sperm and acid phosphatase, is warranted in all cases of female sexual assault presenting within 36 hours of the assault. Institutions dealing with victims from a transient, lower socioeconomic population should offer prophylactic treatment for sexually transmitted disease and pregnancy rather than rely on compliance with follow-up schedules. PMID- 1590617 TI - Management of the patient with the complaint of sexual assault. American College of Emergency Physician. PMID- 1590618 TI - The ring of C2 and evaluation of the cross-table lateral view of the cervical spine. AB - The cross-table lateral view is essential in the initial workup of a trauma patient with a suspected cervical-spine injury. The identification of the radiographic "ring" of C2 on the cross-table lateral view is discussed. When a type III odontoid fracture is present, the ring of C2 is disrupted. We propose that "identification of the ring of C2" should be added to the emergency physicians' systematic checklist when clearing a cross-table lateral view of the cervical spine. PMID- 1590619 TI - Trauma care systems quality improvement guidelines. American College of Emergency Physician. AB - While facility QI has been an important tool in the improvement of the care of the trauma patient, it is essential that system QI also be pursued within each trauma care system. These suggested system QI indicators will provide system medical directors and managers with a valuable tool to facilitate the implementation or improvement of the system QI program. Such a program will allow systems to review their overall function, including management, prehospital, and rehabilitative phases. Through this methodology, both individual providers and the overall trauma system can identify deficiencies and institute appropriate modifications to optimize care of the trauma patient. PMID- 1590620 TI - Trauma care systems quality improvement guidelines: ensuring quality care in the trauma care system. PMID- 1590621 TI - Meeting the needs of the sexual assault victim. PMID- 1590622 TI - Unexpected emergency department death: incidence, causes, and relationship to presentation and time in the department. AB - STUDY OBJECTIVE: To determine the incidence and causes of unexpected death in emergency department patients and its relationship to initial ED presentation. To determine if length of ED stay is directly related to unexpected death. DESIGN: Retrospective chart review of all patients dying in the study ED during a three year period. Patients receiving CPR on admission or who had "do not resuscitate" orders were classified as expected deaths. Vital signs, level of consciousness, length of time in the ED, and cause of death were recorded for all unexpected deaths. SETTING: Five hundred sixty-six-bed medical center with an ED volume of 45,000 patients per year. PARTICIPANTS: Four hundred eleven patients were pronounced dead from 1987 to 1989, and 403 (98%) charts were available. RESULTS: Fifty-seven (14%) patients met the unexpected death criteria. Abnormal vital signs or altered level of consciousness was observed in 56 (98%) patients on presentation. Medical causes accounted for 42 (74%) of the unexpected deaths. Five (9%) surgical and ten (18%) trauma-related deaths were identified. The yearly incidence of unexpected death was 4.9 (per 10,000 ED visits) in 1987 and 4.1 in both 1988 and 1989. Average length of time in the ED before unexpected death increased during the study period (1987, 91 minutes; 1988, 110 minutes; 1989, 116 minutes). CONCLUSION: Unexpected ED death was uncommon, usually nontraumatic, and occurred in patients with evidence of significant illness. Although average length of stay in the ED increased, there was no increase in the incidence of unexpected ED death. If lengths of ED stay continue to increase, this situation will require further study. PMID- 1590623 TI - Emergency department complaint frequency: variation by patient median household income. AB - STUDY OBJECTIVE: To determine whether emergency department complaint frequency varies with patient median household income, as approximated by patient residence zip code. DESIGN: All patient visits and complaints received in one ED were reviewed. Median household income of patient residence zip codes was obtained from available demographic data. Patients were categorized into seven income categories. EXCLUSIONS: Cases in which zip codes could not be determined or zip code income data could not be obtained; complaints from physicians, not patients; and data from zip codes remote from the hospital. SETTING: Nine hundred twenty nine-bed teaching hospital. TYPE OF PARTICIPANTS: All ED visits and all ED complaints over a four-year period. STATISTICAL ANALYSIS: Armitage's chi 2 test for trend of proportions was used to compare complaint frequencies in different income groups. RESULTS: A total of 277,210 patient visits and 675 complaints met study criteria. Complaint frequencies ranged from 1.65 to 3.14 per thousand visits. Higher-income patients were more likely to complain than lower-income patients (P = .0000058). CONCLUSION: In this setting, ED patients residing in higher median income zip codes are more likely to register complaints than those from lower-income zip codes. Complaint frequencies from hospitals with different demographics may not be comparable. PMID- 1590624 TI - Resident management of emergency department patients: is closer attending supervision needed? AB - STUDY OBJECTIVE: To determine the extent of supervision necessary for emergency medicine residents practicing in the emergency department. SETTING: ED of a university-affiliated tertiary care facility with an annual census of 32,000 visits. STUDY POPULATION: All ED patients presenting during study hours during a four-month period. DESIGN: A prospective study was conducted of changes made by emergency medicine attendings in the management of ED patients seen initially by second-year emergency medicine residents. Second-year emergency medicine residents presented all patients seen by them to a specified emergency medicine attending, who also interviewed and examined these patients. Initial patient care was designed by the resident and modified by the emergency medicine attending. Attending modification was recorded by the emergency medicine attending in the study log. Modifications of the residents' proposed care were designated as major (change resulted in an alteration in patient disposition, detection of unsuspected pathology, or marked revision of intended treatment); minor (change resulted in lesser modification of patient management); or no change. RESULTS: Four hundred eight patient encounters were included in the study. Sixteen patients (4%) had major modifications of their care, 134 (33%) had minor modifications, and 258 (63%) had no change. CONCLUSION: Supervision is required for all patients managed by second-year emergency medicine residents, regardless of complaints. This evaluation should include a direct patient interview and examination by the emergency medicine attending and should not be limited to a case discussion or ED record cosignature. PMID- 1590625 TI - Prehospital recognition of multifocal atrial tachycardia: association with acute myocardial infarction. AB - Patients with chronic obstructive pulmonary disease and acute decompensation commonly present with an irregularly irregular supraventricular tachycardia that is, in fact, multifocal atrial tachycardia, but frequently misdiagnosed as atrial fibrillation. To heighten awareness of this arrhythmia, its clinical and electrocardiographic presentations, and its potential therapeutic implications, two patients are reported who presented with multifocal atrial tachycardia during prehospital care. In these two patients the clinical substrate was not chronic obstructive pulmonary disease but instead acute myocardial infarction. By means of a high index of clinical suspicion and close scrutiny of an electrocardiogram, a diagnosis of multifocal atrial tachycardia can be established during prehospital management, and potentially ineffective therapeutic interventions can be avoided, both during prehospital care and in the emergency department. PMID- 1590626 TI - Isolated anterolateral proximal fibular head dislocation. AB - A 28-year-old woman fell and sustained an isolated anterolateral dislocation of the proximal fibula. This injury generally presents with a characteristic history and associated physical examination and radiographic findings, but the subtle nature of the salient findings contributes to a high degree of misdiagnosis. Emergency physicians should be familiar with this injury because early reduction reduces long-term morbidity. PMID- 1590627 TI - Diagnostic use of emergency department echocardiogram in massive pulmonary emboli. AB - Massive pulmonary embolism represents a small percentage of patients presenting to the emergency department with clinical symptoms suggestive of embolic phenomenon. Definitive therapy with thrombolytics or embolectomy is usually delayed until angiographic verification of the clinical suspicion can be obtained. A case is described in which embolectomy was based on clinical diagnosis and confirmatory echocardiogram obtained in the ED. The rapid diagnostic role of echocardiographic data in a subset of patients presenting with clinical symptoms suggestive of massive pulmonary emboli deserves further evaluation. PMID- 1590628 TI - Chemical burn from automotive air bag. PMID- 1590629 TI - Only one type of medical education. PMID- 1590630 TI - Aspiration of radiolucent foreign body. PMID- 1590631 TI - Congenital anomalies of the optic nerve in one family. AB - We present three cases of congenital optic disc anomalies in one family who underwent an extensive diagnostic workup to exclude any intracranial pathology. One patient had elevated optic nerve heads and was hospitalized for multiple diagnostic tests including a lumbar puncture and magnetic resonance imaging scan. This patient had a sister with a previous history of having undergone head and orbital computed tomography to evaluate her symptoms of headaches with anomalous optic nerve heads. The third patient was the father of the other two patients who had previously undergone an extensive evaluation for elevated optic nerve heads and was treated for presumed pseudotumor cerebri with fenestration of the optic nerve sheath. These cases underscore the importance of a detailed family history and examination of family members to exclude congenital abnormalities of the optic nerve head before beginning an extensive workup. PMID- 1590632 TI - Hyphema as the presenting sign of acute myelocytic leukemia. PMID- 1590633 TI - Acquired ocular syphilis: diagnosis and treatment. AB - We present our findings in 14 patients with a serologically verified diagnosis of ocular syphilis. Although most patients had iridocyclitis, other ocular findings included episcleritis, scleritis, vitritis, retinitis, papillitis, panuveitis, cystoid macular edema, and retinal detachment. Most patients had only ocular manifestations of syphilis with no other definitive symptoms. Without the use of specific treponemal serologic tests, the diagnosis of ocular syphilis would have been missed in at least 20% of patients. Furthermore, 80% of patients were negative for antibody to syphilis in the cerebrospinal fluid, and therefore, this test should not be used to determine treatment for ocular syphilis. Currently, the most effective therapy for ocular syphilis is the same as that for neurosyphilis (i.e., high-dose intravenous penicillin G 12 to 24 million units/day for ten to 14 days). Human immunodeficiency virus-positive patients should receive a full 14 days of high-dose intravenous penicillin G plus intramuscular benzathine penicillin 2.4 million units weekly for three weeks because their immune defenses are likely to be impaired. PMID- 1590634 TI - Spontaneous iris stromal cyst: a case report and review of literature. AB - Spontaneous iris stromal cysts are rare and usually are identified early in life. They resemble implantation iris cysts after nonsurgical and surgical trauma; both have an epithelium which usually is conjunctival in nature. However, in spontaneous iris stromal cysts, no ocular trauma history is found. We present a case report and review of literature. PMID- 1590635 TI - Wasp sting-induced linear keratitis. AB - A 52-year-old man was stung by a wasp on his left conjunctiva. On the day of the injury, severe chemosis and perilimbal cell infiltration were observed. On the next day, a peculiar linear keratitis was seen. Systemic and topical corticosteroids were applied successfully. PMID- 1590636 TI - Remarkable postcataract against-the-rule astigmatism after phacoemulsification in 83 of 809 cases. AB - We analyzed 83 cases of remarkable postcataract against-the-rule (AR) astigmatism (greater than 1.5D) occurring in a total of 809 Kelman's phacoemulsification aspiration procedures, all using 10-0 polyester sutures in a double-running fashion to close the corneoscleral incisions. All operations were done by one surgeon, using the same surgical procedure and the same number of sutures. The induction and spontaneous regression of several types of astigmatism were analyzed over six months. In cases of preoperative oblique and AR astigmatism, shifts (2.09 +/- 0.22D, 1.93 +/- 0.13D, respectively) after the first week were much smaller than those of preoperative with-the-rule astigmatism. Thereafter, degrees of oblique and AR astigmatism increased and remained higher even six months after surgery. The induction and spontaneous regression of postoperative AR astigmatism was similar to that of oblique astigmatism. Compression of the lids on the eye may be a more important factor than previously considered. PMID- 1590637 TI - Episcleral pseudorheumatoid nodule with a choroidal mass simulating malignant melanoma. AB - A 47-year-old man had an injected episcleral mass, anterior uveitis, and a grayish white elevated choroidal mass with exudative retinal detachment. Excisional biopsy of the episcleral mass showed pseudorheumatoid nodule. All investigations for rheumatic diseases were negative. Treatment with topical corticosteroids resulted in disappearance of the choroidal mass and resolution of the uveitis. An 11-year follow-up showed no evidence of any rheumatic disease. To the best of our knowledge, this is the first histopathologically confirmed case report where an episcleral pseudorheumatoid nodule presented with a choroidal mass that simulated choroidal malignant melanoma. PMID- 1590638 TI - The effect of arm exercise and ocular massage on postural hand tremor. AB - In this pilot study, the effect of exertion on hand tremor was investigated. Postural head tremor was measured in eight ophthalmology residents before and after lifting a barbell and before and after massaging a phantom eye. All subjects showed an increase in postural hand tremor after lifting a barbell for five minutes (mean, 79% +/- 59%). Postural hand tremor increased 38% +/- 79% after ocular massage, which was not statistically significant (P greater than .5). The peak pressures generated during ocular massage ranged from 25 to 265 mmHg (mean, 134 +/- 80.4 mmHg). There was also no correlation between change in postural hand tremor and the pressure generated by ocular massage (P greater than .2). The authors conclude that strenuous arm exercise, such as lifting a barbell, increases postural hand tremor and should be avoided before doing microsurgery; ocular massage is not sufficient exercise to affect postural hand tremor adversely. PMID- 1590639 TI - Cardiac rehabilitation and preventative cardiology. PMID- 1590640 TI - Trends and paradigms in cardiac rehabilitation and preventive cardiology. PMID- 1590641 TI - Hyperinsulinaemia in non-obese subjects with hypertriglyceridaemia: a preliminary report. AB - It has been known for some time that hyperinsulinaemia is associated with hypertriglyceridaemia. However, previous studies looking at the relationship between hyperinsulinaemia and hypertriglyceridaemia have included overweight subjects. The effect of obesity on the insulin status of hypertriglyceridaemic patients is uncertain. We investigated the insulin status of hypertriglyceridaemic subjects in the absence of confounding factors such as obesity, hypertension and diabetes mellitus. Our results demonstrate that basal insulin levels as well as the insulin response after an intravenous glucose challenge are higher in moderately hypertriglyceridaemic patients when compared to age and body mass index matched controls. Hyperinsulinaemia may have pathogenetic significance for hypertriglyceridaemia as well as other features of a constellation of metabolic derangements such as obesity, hypertension and glucose intolerance. PMID- 1590642 TI - Community exercise to prevent heart disease. How much should we advise? AB - There is international agreement that those in the community who are habitually active, either in work or in leisure, have a better coronary risk profile and a lower death rate from coronary heart disease (CHD). This agreement is usually translated into recommendations encouraging the population to perform regular aerobic exercise for 30 minutes thrice weekly. Such a policy is intrinsically costly, requiring detailed medical examination, exercise testing and exercise prescription. Such a policy may detect patients with asymptomatic CHD on the basis of silent myocardial ischaemia for whom there is no proven therapy. More often, exercise testing of asymptomatic "well" middle aged populations may well result in a large number of positive tests suggesting the existence of heart disease which is later proven by more expensive testing to be non existent. And finally, only a minority of the population actually exercises aerobically and this proportion falls with the ageing of the population. In summary, such a policy, whilst supported by observational data, is costly and ineffective. Review of the observational studies on physical activity or physical fitness reveals that most, but not all, of the studies show that any level of activity of fitness above basal is protective from CHD--in other words, there appears to be no threshold of activity or fitness for cardiovascular protection. Furthermore, there is a close relationship between the total amount of physical activity performed, the amount of higher intensity aerobic activity performed, and physical fitness. As such, it would appear that we could advise the community to increase the total amount of physical activity to achieve cardiovascular protection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590643 TI - Lipoprotein metabolism: an overview. AB - The major plasma lipids, cholesterol and triglyceride, circulate in association with specific proteins as lipid-protein or lipoprotein complexes. The proteins direct and regulate the metabolism of these complexes in interacting with tissue enzymes and receptors. The metabolic fate of circulating triglyceride is governed by the activity of the enzyme lipoprotein lipase, situated in adipose tissue and skeletal muscle. Cellular demand for cholesterol, on the other hand, is met by activation of a specific receptor which mediates the delivery of sterol-rich lipoproteins to lysosomal degradation in liver and peripheral tissues. In order to prevent excess cholesterol accumulation at the periphery, there is a system of reverse cholesterol transport which involves assimilation and trapping of the sterol in the plasma lipoproteins through the action of the enzyme lecithin: cholesterol acyltransferase. Thereafter, the cholesterol is delivered to the liver, the only organ capable of excreting it in significant amounts. Disturbances in these processes may produce gross changes in the plasma lipid profile, clearly recognisable as hyperlipidaemia. However, it is becoming increasingly clear that a number of inherited traits can subtly perturb the lipoprotein spectrum and increase coronary risk even in subjects whose plasma lipoprotein profile would be considered normal. PMID- 1590644 TI - Cardiovascular risk reduction through lifestyle change in clinical settings. AB - A large amount of observational and experimental research has demonstrated that lifestyle factors are important determinants of cardiovascular disease. In particular, epidemiological evidence from large, controlled multiple risk factor intervention trials and research examining the effects of secular changes in lifestyle on changing morbidity and mortality rates indicate that changes in lifestyle can reduce the risk of coronary heart disease (CHD). This paper provides an overview of the lifestyle change process and provides guidelines for increasing the efficacy of lifestyle change interventions in clinical settings. PMID- 1590645 TI - Multivariate models for compliance with phase 3 cardiac rehabilitation services in Johannesburg. AB - The efficacy of an exercise cardiac rehabilitation programme depends on an adequate compliance of its participants. A 50% dropout rate after 12 months has been reported by most rehabilitation programmes. Compliance with attendance and the exercise prescription are monitored daily at the Johannesburg Cardiac Rehabilitation Centre. This study evaluated the attendance of 711 patients admitted to the programme between June 1986 and March 1990 and looked at possible differences in attendance and intensity rates of compliers and dropouts prior to dropout. Multiple regression analyses were performed on all patients using different measures of exercise compliance as dependent variables and patient characteristics on admission as explanatory variables in order to establish possible associations which could identify potential dropouts at an early stage. We found that 36% of patients dropped out by 12 months and that 50% managed to complete our 18 month programme. Dropouts complied less than compliers in terms of attendance and intensity before dropping out. Significant associations were found between the measures of compliance and patient characteristics. Age, smoking, peak oxygen uptake and a measure of hostility were identified as predictive factors. With the exception of the energy expended per session the variation in the other measures of compliance was poorly explained by the explanatory variables suggesting that other factors could be related to compliance at the Johannesburg Cardiac Rehabilitation Centre and need to be further evaluated. PMID- 1590646 TI - The role of the Singapore Sports Council in coronary artery disease prevention. AB - The Singapore Sports Council (SSC) is a statutory board (government body) which was set up in 1973. Its main responsibility is to implement the "SPORTS FOR ALL" policy of the Singapore Government. Physical activity has been found to be an important factor in coronary artery disease prevention. It is through its "SPORTS FOR ALL" policy, by promoting physical activity to all Singaporeans, that the SSC helps in coronary artery disease prevention. The SSC promotes physical activities (and sports) by providing facilities, running fitness schemes, organising instructional schemes for sports, sports training schemes and sports activities. The facilities available to the public include swimming pools, stadia with running tracks and playing fields, tennis courts, squash courts and badminton courts. A 1987 national survey showed that 28.3% of the population aged 15 and above engaged in sports one or more times a week. Those who exercised three or more times a week accounted for only 7.9%. The SSC will continue in its efforts to improve this rate of physical activity in the population, with coronary artery disease prevention as one of its main objectives. PMID- 1590647 TI - The role of omega 3 fatty acids in the prevention and rehabilitation of coronary artery disease. AB - Coronary artery disease, the leading cause of death in the world, poses a major socioeconomic problem which has prompted extensive research into both preventive and therapeutic measures. Among the former are dietary modifications, including fish oil supplements which have been strongly advocated to prevent the development of atherosclerosis. This article reviews the pathophysiological basis of the evidence for recommending fish and fish oil supplement in the prevention of atherosclerosis. PMID- 1590648 TI - Quality of life in chronic cardiovascular illness. AB - Aspects of outcome that require assessment in chronic cardiovascular illness include the total consequences of both the illness and its management. Quality of life in the medical care context, addresses the resultant comfort, sense of well being and life satisfaction; the maintenance of reasonable physical, emotional, and intellective function; and the ability to participate in valued activities in the family, workplace, and community. Factors reinforcing the validity of considering quality of life attributes relate to the contemporary marked increase in the prevalence of chronic cardiovascular illness. In chronic illness, the therapies administered are not curative but are rather designed to limit the disabling consequences of the disease; the perceptions of patients about their resultant health status thus have clinical relevance. Next is that patients, as enlightened consumers, increasingly seek information about the options available to them for treatments for chronic cardiovascular disease, with their queries relating both to the biomedical (morbidity and mortality) outcomes and to the psychosocial (life quality) outcomes. Finally, quality of life attributes are increasingly examined in evaluating the cost effectiveness of cardiovascular care, in addition to morbidity and mortality data; determining features involve the resultant functional independence of the individual as a result of care, productivity, return to remunerative work, and level of life satisfaction. PMID- 1590649 TI - Effect of acute reduction in oxygen transport on parameters of aerobic function during exercise. AB - The binding of haemoglobin by carbon monoxide reversibly decreases the blood O2 carrying capacity, providing a useful model of impaired circulatory O2 transport. We evaluated noninvasive parameters of aerobic function during exercise to detect small changes in O2 transport, using carbon monoxide. Ten normal subjects performed both symptom-limited incremental and two levels of constant work rate on a cycle ergometer while breathing air and air with added carbon monoxide to cause carboxyhaemoglobin (COHb) to be approximately 11% (level of heavy cigarette smoker) and 20%. Maximal O2 uptake (VO2 max), the anaerobic threshold (AT) determined from the plot of CO2 output as a function VO2 (V-slope, the ratio of increase in VO2 to work rate increment (delta VO2/delta WR) and the upper slope of the V-slope analysis were measured while progressively increasing work rate. These changed in approximately the same percent as the increase in COHb. For the constant work rate tests, the time constant of VO2 and the difference in VO2 at six minutes as compared to three minutes of exercise (delta VO2 (6-3)) were significantly increased when COHb was increased. These noninvasive parameters of aerobic function, determined from the cardiopulmonary response to incremental and constant work rate exercise, particularly when used in combination, proved to be sufficiently sensitive to objectively detect small changes in O2 transport to the working muscles during exercise. PMID- 1590650 TI - Supervised versus unsupervised exercise training following myocardial infarction and myocardial revascularisation procedures. AB - Exercise training is an important component of rehabilitative care for patients following myocardial infarction or myocardial revascularisation procedures. Participation of the patient in supervised exercise training, however, is not always practical, and home exercise training may be a reasonable alternative for low-risk patients. The relatively routine predischarge exercise test, performed for risk stratification, can identify low-risk patients and guide their exercise prescription during the early weeks at home. Advantages of home exercise training include increased availability and convenience and lower cost. Comparable improvements in functional capacity have been documented to result from home exercise and supervised group programmes. Drawbacks, however, involved the limited ability to teach patients the necessary safety precautions for exercise, the lack of opportunity to teach and encourage modification of coronary risk related behaviours and lifestyles, and the lack of peer support. Several techniques have been proposed to overcome some limitations of home exercise and to encourage long-term adherence to the exercise regimen. Among these are telephone interaction between patients and nurses or other health professionals, transtelephonic exercise ECG recording, and the use of home exercise training videocassette. Comparative studies of the safety, efficacy, and costs of these approaches are needed; and means must be devised to provide the nonexercise related information and counselling available to coronary patients in a supervised exercise setting. PMID- 1590651 TI - Food consumption patterns in an affluent society and barriers to overcoming dietary change. AB - In affluent nations, there has been an increasing awareness of the links between diet and the incidence of chronic diseases such as heart disease, hypertension and cancer. In some of these countries, this has led to improvements in the dietary profiles of the community and its health-related status. Studies of random samples of the Australian population carried out in the last decade or so have shown a downward trend in the consumption of total and saturated fats and salt and an increase in polyunsaturated fat and fibre. However, detailed assessment of food consumption patterns reveal that the changes in dietary patterns relate predominantly to improvement in choice within food categories rather than a fundamental change in the relative amounts of foods consumed across categories such as meats, dairy foods, cereal grains and fruits and vegetables. The surveys show that knowledge about the links between diet and disease is encouragingly high in most sectors of the Australian community as is concern about the healthiness of the food supply but time constraints, the perception that "healthy" foods are boring foods, lack of information on packaging and family pressures were seen as major barriers to dietary change. A further barrier is lack of knowledge about the balance of foods required and in particular, the value of cereal foods. Analysis of the dietary data show that further significant improvements in the dietary profile are only likely to accrue from a fundamental change in the relative use of the major food categories. PMID- 1590652 TI - Transient hypoalgesia under physical exercise--relation to silent ischaemia and implications for cardiac rehabilitation. AB - A series of studies with humans as well as experiments carried out on animals could show that physical exercise leads to temporary hypoalgesia. Reduced sensitivity to pain is not only demonstrable after long-distance exercise (such as marathon run) but also after intensive physical exercise on a laboratory ergometer. Pain threshold elevation is most pronounced during maximal exertion, but hypoalgesia remains present also after exercise is stopped demonstrating that a systemic analgetic effect is induced by the exercise process. Pre-exercise pain threshold level is returned to approximately 60 minutes after the exercise. The cause of the exercise-induced hypoalgesia is probably an activation of central pain inhibitory mechanisms by the "stimulus" of physical exercise (stimulation- or stress-induced analgesia). Central pain inhibitory systems are thereby triggered by the stimulation of afferent nerve endings (group III and IV) in the skeletal muscle. The same trigger mechanism also plays a role as a release stimulus for hormones such for beta-endorphin which is increased under physical exercise. Plasma-beta-endorphin is probably not directly involved in the exercise induced hypoalgesia but is rather a "marker" for the activating of central analgesia mechanisms. Stress-induced hypoalgesia plays also a role in the coronary heart disease. The activation of endogenous analgetic mechanisms leads to a part of the myocardial ischaemia provoked by exercise being silent under exercise. Completely asymptomatic myocardial ischaemia patients display a generalized hypoalgesia which is demonstrable independent of an exertion stimulus and which indicates a central set-point change in the antinociceptive system. PMID- 1590653 TI - Efficacy and cost-effectiveness of simvastatin and gemfibrozil in the treatment of hyperlipidaemia. AB - The aim of this study is to compare the efficacy and cost-effectiveness of simvastatin with gemfibrozil in regulating the serum lipid profiles in the local population. In this study, we reviewed the effect of medication on 75 patients with hypercholesterolaemia with or without hypertriglyceridaemia; 26 patients were on simvastatin 10 mg nightly, 24 patients were on gemfibrozil 300 mg twice daily and 25 patients were on gemfibrozil 600 mg twice daily. The average follow up period was 10.8 weeks, 19.0 weeks and 16.2 weeks for simvastatin 10 mg, gemfibrozil 300 mg and gemfibrozil 600 mg groups respectively. Prior to drug therapy, patients were put on dietary control. The pre-treatment and post treatment serum lipid profiles were monitored. The mean changes in the lipid profiles of the patients on gemfibrozil 600 mg twice daily were a 21.6% reduction in total cholesterol, a 21.8% reduction in low-density lipoprotein cholesterol (LDL-C), a 46.3% reduction in serum triglyceride and an 11.2% increase in high density lipoprotein cholesterol (HDL-C). The patients in all three groups had raised HDL-C and lowered triglyceride levels post-treatment but patients on gemfibrozil had a greater increase in HDL-C and a greater decrease in triglycerides as compared to the simvastatin group. In comparison to gemfibrozil, simvastatin was more efficacious in the reduction of LDL-C. The mean reduction in the LDL-C was 21.8% for gemfibrozil 600 mg twice daily group as compared to 28.0% for simvastatin 10 mg nightly group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590655 TI - Exercise training and the prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA). AB - To evaluate whether exercise training prevents the restenosis after percutaneous transluminal coronary angioplasty (PTCA), treadmill exercise with thallium-201 myocardial scintigraphy was performed at first and thirteenth week after PTCA in 18 patients with training and in 20 patients without training. Total treadmill exercise duration and maximal pressure rate product 13 weeks after PTCA increased significantly in the trained group, whereas there was no significant change in the untrained group. ST segment depression from the baseline did not change significantly in both groups. Myocardial perfusion obtained by Tl-201 scintigraphy improved significantly in the trained group, whereas there was no significant change in the untrained group. The restenosis rates at the third month after PTCA was 17% (3/18) in the trained group and 40% (8/20) in the untrained group. It is concluded that in patients with coronary artery disease, exercise training improves myocardial perfusion by preventing the progression of coronary artery stenosis after PTCA. PMID- 1590654 TI - The efficacy of aerobic exercise therapy on hypertensive patients with mild cardiac complications. AB - To investigate the antihypertensive efficacy of aerobic exercise therapy in essential hypertensives, 20 patients underwent eight weeks of cycle ergometer training at anaerobic threshold (AT) point. Cardiopulmonary exercise testings with ramp protocol were performed before and at two/four/eight weeks during the training period in order to determine AT and to evaluate the changes in blood pressure (BP), heart rate (HR), oxygen uptake (VO2; ml/min/kg), and O2 pulse (ml/min/beat) during exercise. 75g glucose tolerance test (OGTT) was measured before and after exercise therapy. The mean values of systolic blood pressure, oxygen uptake, O2 pulse, before and after exercise therapy were as follows: systolic blood pressure at rest = 160 +/- 19 mmHg and 135 +/- 11 mmHg, systolic blood pressure at AT = 195 +/- 13 mmHg and 180 +/- 10 mmHg, oxygen uptake AT = 12.0 +/- 0.9 ml/min/kg and 14.4 +/- 1.0 ml/min/kg, O2 pulse at AT = 6.8 +/- 1.5 ml/min/beat and 7.6 +/- 1.88 ml/min/beat. After exercise therapy, systolic blood pressure decreased (p less than 0.01), while O2 pulse and VO2 increased (p less than 0.01). Hyperresponse of serum insulin to glucose also improved. These results show that aerobic exercise therapy at AT level has beneficial effects on high blood pressure and improves exercise tolerance and hyperresponse of serum insulin to glucose without any complications. PMID- 1590656 TI - Cardiopulmonary resuscitation--training and certification in Malaysia. AB - Cardiopulmonary resuscitation training in Malaysia was started at the General Hospital Kuala Lumpur in 1986. Now the programme has been extended to all the General Hospitals in the country and is fully supported by the Ministry of Health. The American Heart Association curriculum for Basic Life Support is followed. From February 1986 till March 1991, the programme has trained 3982 in Basic Life Support and 548 in Advanced Cardiac Life Support. We are making efforts to translate some of the American manuals into the National language. A preliminary survey on early defibrillation indicates that majority of the physicians will allow defibrillation by non-physician. PMID- 1590657 TI - Lipid screening in a volunteer population in Singapore. AB - Coronary risk profile screening was performed in 1065 volunteers during the National Heart Week 1988 as part of the National Heart Association's campaign against the increasing incidence of ischaemic heart disease. Of particular importance was the use of a desktop analyser for lipid screening of total cholesterol and high density lipoprotein (HDL) cholesterol. It was found that the mean serum cholesterol was 211 +/- 39.5 mg/dl, with 62% of the participants having a total cholesterol greater than 200 mg/dl and 23.1% having a total cholesterol greater than 240 mg/dl. For HDL cholesterol, the mean was 48.4 +/- 17 mg/dl, with 18.7% of the participants having a low HDL cholesterol of less than 35 mg/dl. The male Indians had a significantly lower HDL cholesterol compared to male Malays. Three or more risk factors for coronary artery disease was present in 21.7% of Chinese, 41.2% of Malays and 50% of Indians. We conclude therefore that a proportion of this volunteer population, the majority of which have no overt heart disease, is at risk from coronary artery disease from an elevated cholesterol or low HDL cholesterol level. A follow-up of 90 participants who were initially detected to have an elevated cholesterol in 1986, however, showed that only 54.4% still had an elevated cholesterol of greater than 240 mg/dl, thus suggesting that early detection may help to reduce this risk. PMID- 1590658 TI - Cardiac life support training: the Ministry of Health's experience. AB - This study reviews the records of all cardiac life support training courses conducted at the Ministry of Health's Life Support Training Centre situated in Singapore General Hospital over a six period from 1985 to 1990. A total of 1,789 persons were trained in Basic Life Support (BCLS), 65 as BCLS Instructors, 267 in Advanced Cardiac Life Support (ACLS), 276 in Emergency Cardiac Care (ECC) and 24 in Emergency Cardiac Defibrillation (ECD). These courses have involved a total of 1111 doctors, 1248 nurses and 62 ancillary staff. At the end of the course, 90.7% of those learning BCLS agreed that they would use their CPR skills, if required. Only 60% felt they would use mouth-to-mouth ventilation. Of 415 who expressed an interest in becoming instructors, 15.7% have, to-date, been trained. While more than 80% of persons learning, ACLS were doctors, only 25% of these were willing to instruct. There are currently 14 ACLS instructors. The ECC courses were modified from the ACLS course and taught to Emergency Room doctors only. It was found to be immensely popular with 98% expressing benefit. The ECD programme trained emergency ambulance nurses in the use of semi-automatic electrical defibrillators. The marked increased in yearning for cardiac life support skills amongst medical and nursing staff has been a major factor in the proliferation of life support training programmes at the Centre. Nurturing this enthusiasm is the key to ensuring that the programmes continue to expand for the benefit of both inpatients and the out-of-hospital lay public. PMID- 1590659 TI - Economic benefits of secondary and tertiary cardiac rehabilitation: a critical study. AB - At least seven criticisms have been advanced to those suggesting economic benefit from secondary and tertiary rehabilitation: (i) many existing data sets are weak, (ii) many analyses have been limited to self-selected exercise participants, (iii) the distribution of benefits between different sectors of the economy has been ignored, (iv) programme participation is not necessarily synonymous with economic benefit, (v) the discount rate has been neglected, (vi) opportunity costs have not been considered, and (viii) possible increases in pension costs could outweigh supposed benefits. Although there are limitations in the original calculations of economic benefit, there are also weaknesses in their critique. Cost-effectiveness analysis has some attractions over cost-benefit analysis, because areas of fiscal and ethical uncertainty are avoided. Given that patients who develop chronic diseases will require some form of treatment, exercise offers an attractive option for both secondary and tertiary prevention, particularly if programmes have low facility and opportunity costs, and attention is directed to high-risk segments of the population. The challenge to incorporate the lessons from such analyses into governmental and corporate-decision making. PMID- 1590660 TI - Long term impact of a fitness programme--the Canada Life Study. AB - Information gathered over twelve years operation of the Canada Life Assurance fitness programme is reviewed. Motives leading to programme initiation included sale of a health-related product, managerial interest, and government and university support. Participation is now a little under capacity, at about 13% of eligible staff. Except in a small minority of members, the impact upon physical condition and lipid profile has been marginal. The reported community exercise participation of employees has increased since initiation of the programme. An early reduction of employee turnover has been sustained in programme participants. A reduction of absenteeism is limited to enthusiastic participants, with a 0.13% payroll saving for the company as a whole. An early analysis suggested a substantial Hawthorne effect, but a 2.7% gain of productivity relative to a matched control company. Medical insurance claims were also lowered in the first year after introduction of the programme, probably because of gains in perceived health. The Canadian Health Hazard Appraisal instrument showed a two year reduction of appraised age in male participants. The gymnasium area was developed at a cost of about $175,000, or $700/m2 1990 Canadian dollars, and the current operating budget is about $110,000/year. The 400 members each pay $55/year, and the company provides an operating subsidy of about $200/member. Overall findings suggest the programme remains cost-effective and cost beneficial. PMID- 1590661 TI - Prehospital cardiac arrest: the chain of survival concept. AB - Sudden cardiac death claims 1,000 lives per day in the United States and cardiovascular disease remains the number one cause of death in the United States. Morbidity and mortality will be reduced when a coordinated response to out-of-hospital cardiac arrest has been achieved nationwide. The implementation of an integrated system, the chain of survival which includes early access via a universal Emergency Medical Service (EMS) number, trained individuals to provide Cardiopulmonary Resuscitation (CPR), widespread early defibrillation and utilisation of automated external defibrillators, and early advanced care will yield survival rates in excess of 30%. The potential for saving 100,000-200,000 lives per year is achievable provided the chain of survival concept is adapted. PMID- 1590662 TI - Pharmacological aspects in secondary prevention of coronary artery disease. AB - Recent studies have demonstrated a trend toward improved survival in coronary artery disease. Contributing to this trend are advances in medical therapy. In order to evaluate the preventive effect of drugs in secondary prevention of coronary heart disease, many multi-centered trials were conducted. There is evidence that beta-adrenergic blocking agents may decrease mortality following myocardial infarction. Platelet-active drugs reduce the rate of reinfarctions and may have a beneficial effect on survival. In contrast lipid lowering agents, anticoagulants, antiarrhythmic drugs and calcium channel blockers have not shown convincing beneficial effect on the survival of patients following myocardial infarction, and further studies are required to determine the effect of the various modalities in different clinical settings. PMID- 1590663 TI - Protection: risk ratio of antihypertensive drug treatment in the elderly. AB - In recent controlled trials using clinic-based manometry, thiazides and beta blockers prevented cerebrovascular and coronary deaths in patients aged 60-79 years with cryptogenic hypertension (diastolic 90-119 mm Hg). Elderly patients should usually take low-dose thiazide with potassium replacement. beta-Blockers also postpone death, but may mask hypoglycaemia. Calcium blockers and low-dose angiotensin-converting enzyme (ACE) inhibitors appear preferable in diabetes, and thiazides or ACE inhibitors in heart failure or peripheral vascular disease. Maintaining average diastolic pressure at 80-84 mm Hg impairs function of the kidneys, and possibly the myocardium. Metabolic reactions worsen with age. Drug treatment should match individual daily function. By clinic manometry, the protection:risk ratio of antihypertensive treatment progressively decreases with age, reaching less than 1.0 in patients over 80-85 years. Twenty-four-hour ambulatory blood pressure information should guide treatment more reliably in patients greater than or equal to 60 years. PMID- 1590665 TI - The development of standards and guidelines for cardiopulmonary resuscitation and emergency cardiac care in the United States. AB - There have been four major conferences since 1966 which have produced standards and guidelines for cardiopulmonary resuscitation and emergency cardiac care. These events and publications have served as the principal source and direction for the American Heart Association to develop training programmes for the treatment of sudden cardiac death. The process of standard setting and programme implementation has been very successful in stimulating lay public, health care professional and paraprofessional interest in cardiopulmonary resuscitation techniques. The results of the national campaign may result in as many as 100,000 to 200,000 lives saved per year and successful resuscitation rates from out of hospital sudden death via the chain of survival concept reaching 30% in the United States. PMID- 1590664 TI - A two-dimensional intervention plan to reduce risk factors for ischaemic heart disease. AB - Although most cardiologists and public health officials are convinced of the great value of reducing risk factors for cardiovascular diseases, efforts to reduce these factors have seldom reached effectively beyond those persons in direct touch with physicians. This paper describes nine channels which health officials can utilise to inform, motivate, and change health behaviours in the general public. The channels are: individuals, family and friends, health professionals and institutions, schools and teachers, business and labour, mass media, local organizations, community leaders, regional and national government. Using all these channels in an integrated programme to reduce multiple risk factors in the community results in a two-dimensional intervention plan in which the various components reinforce one another. Specific programmatic suggestions are made for each of the following cardiovascular risk factors: cigarette smoking, high blood pressure, lack of exercise, high serum cholesterol, and stress. PMID- 1590666 TI - Maintenance of behaviour change in patients with coronary artery disease. AB - This paper comments upon patterns of behavioural change after acute cardiac illness and discusses determinants of longterm compliance with advice. The importance of comprehensive rehabilitation during convalescence is emphasised. Education, motivation and support of the patients are essential for the adoption of healthier lifestyles. Despite comprehensive rehabilitation, however, recidivism to former habits is common, particularly with smoking and physical inactivity. This is partly determined by premorbid social and personality characteristics of patients. Social and behavioural support at the workplace and within the community may well be of significant benefit in supporting patients to maintain their necessary health behaviour changes. Some of the evidence related to these issues is discussed and recommendations are made regarding future directions for patient support. PMID- 1590667 TI - Metabolic effects and disposition of sebacate, an alternate dicarboxylic fuel substrate. AB - Disodium sebacate is a 10-carbon-atom dicarboxylic acid, proposed as substrate for parenteral nutrition. We investigated its pharmacokinetic profile and thermogenic effect during a short-time infusion (5 h at 10 g/h) in 7 male volunteers. Sebacate in serum and urine was measured by high-performance liquid chromatography. A single-compartment model with two linear elimination routes was fitted. Metabolic measurements (VO2, VCO2, respiratory quotient, metabolic rate) were continuously performed for 8 h (5 h during and 3 h after the infusion) by a canopy indirect calorimeter. The apparent volume of distribution of sebacate was 8.39 +/- 0.69 liters, and the plasma fractional removal rate constant was 0.0086 +/- 0.00077 min-1. The average half-life and plasma clearance were 80.6 min and 72 ml/min, respectively. The increase in metabolic rate, the decrease in respiratory quotient and the changes in ketone body, glucagon and insulin levels during the infusion were not significant. 24-hour catecholamine excretion was within normal limits. Calories administered by sebacate seem to be available for utilization without relevant metabolic side effects. PMID- 1590668 TI - Food intake and nutrient sources in the diet of middle-aged men in southern Germany: results from the WHO MONICA Augsburg Dietary Survey 1984/85. AB - Diet records of the WHO MONICA Augsburg dietary survey 1984/85 sample of 899 men aged 45-64 were used to derive quantitative data about food intake and the contribution of food groups to energy intake and the intake of those nutrients relevant to the discussion about nutrition and cardiovascular disease: protein, fat, saturated, mono- and polyunsaturated fatty acids, cholesterol, carbohydrate, polysaccharides and total fiber. The present lists of nutrient sources should be helpful for the development of acceptable dietary advises, which make allowance for actual eating patterns as well as for developing improved instruments of dietary assessment. PMID- 1590669 TI - Effect of different protein diets on the distribution of amino acids in plasma, liver and brain in the rat. AB - The distribution of amino acids between plasma, liver and brain was studied in adult male rats, fed a diet containing 8.7, 17 (control animals), 32 and 51% of protein during 15 days. The caloric intake was nearly equal in all groups. The highest food intake was observed in the animals on the low protein diet. Changes in plasma amino acids were variable. In contrast to the behavior of most amino acids in plasma, the branched chain amino acids were highest in the animals fed the 51% protein diet. Despite the low protein intake in the animals fed a 8.7% protein diet, the concentration of serine, glutamic acid, glutamine, glycine, alanine, methionine, isoleucine, leucine, phenylalanine and ornithine were significantly higher compared to control animals, whereas in those receiving a high protein diet, valine, leucine, tyrosine, tryptophan and histidine increased in relation to the increased protein and amino acid intake. The plasma amino acid patterns are not greatly influenced by the amino acid distribution in the food and the amount ingested. Alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase and cholinesterase showed a two- to fivefold increased activity in the liver of animals consuming a high protein diet. In the brain, the concentration of valine, leucine, isoleucine, phenylalanine and tyrosine in animals receiving the low protein diet was higher than in controls and increased further with increasing protein content of the diet. Glutamine was increased in all dietary groups. The predicted influx of amino acids showed increasing influx rates in dependence of the plasma amino acid concentration. The entry of tyrosine and tryptophan and their brain concentration was inversely proportional to the protein content of the diet. In the present study which considers long-term adaptation to an increasing protein and amino acid intake in comparison to a balanced control protein diet, the levels of the indispensable amino acids were maintained within narrow limits in the brain and liver. The results indicate that inspite of a variable protein intake, the body tends to keep organ amino acids in relatively narrow limits favoring in this way amino acid homeostasis. PMID- 1590670 TI - Riboflavin deficiency and iron absorption in adult Gambian men. AB - Iron absorption from 3.38 mg 58Fe was measured in riboflavin-deficient Gambian men with haemoglobin (Hb) less than 11.5 g/dl before and after oral riboflavin therapy, and the results compared with a group not receiving riboflavin. Riboflavin status (as determined by erythrocyte glutathione reductase activation coefficient) and Hb increased in teh riboflavin-supplemented but not placebo group. Plasma ferritin levels were low and did not change in either group. There was very wide variation in percentage iron absorption between individuals and also within single individuals on two separate occasions but no measurable change with riboflavin supplementation. The results of the study indicate that the efficiency of iron utilization is impaired in riboflavin deficiency, but that iron absorption is unaffected. PMID- 1590671 TI - Impairment of phagocytic process in macrophages from young and old mice by protein malnutrition. AB - In young (15 +/- 2 weeks old) and old (75 +/- 5 weeks old) Swiss mice fed a 4% protein diet ad libitum for 15 days, we studied the different steps of phagocytic processes of peritoneal macrophages. In young mice, adherence to tissue substrates was significantly increased, but spontaneous mobility, chemotaxis, attachment and ingestion of opsonized Candida albicans, and production of superoxide anion indicative of microbicidal capacity measured by the nitroblue tetrazolium (NBT) reduction were significantly decreased with respect to the corresponding young controls (mice fed with a standard 17% protein diet). Attachment and ingestion of C. albicans, and NBT reduction were also decreased in old protein-malnourished mice. PMID- 1590672 TI - Postprandial thermogenesis in leanness and anorexia nervosa. AB - Resting energy expenditure (REE) and postprandial thermogenesis (PPT) after the ingestion of a mixed test meal (3.56 MJ, 850 kcal) were determined in 7 anorectic patients, 7 very lean women and 8 control women. REE is absolute value was sharply decreased in the anorectics, but did not significantly differ between the very lean and the control subjects. On the other hand, when adjusted for body weight, REE only tended (p = 0.18) to be lower in the anorectics in comparison to the control women. PPT was similar in the anorectics (187.2 +/- 24.6 kJ/4 h) and the controls (200.7 +/- 16.8 kJ/4 h), but lower in the lean subjects (137.5 +/- 20.0 kJ/4h: p less than 0.05) than in the other two groups. The present study shows that the thermic response to the ingestion of a mixed test meal was not decreased in undernourished anorectic patients whereas it was significantly reduced in very lean healthy women. PMID- 1590673 TI - Serum total bile acid concentration in rhesus monkeys: effects of feeding cholesterol and inhibiting cholesterol absorption and synthesis. AB - The serum total bile acid concentration was measured in rhesus monkeys fed diets practically free of cholesterol and with added cholesterol at two levels. Also, the effects of inhibiting cholesterol absorption by feeding plant sterols and inhibiting cholesterol synthesis by feeding triparanol upon the serum total bile acid levels were studied. Cholesterol feeding significantly increased the serum bile acid concentration. The serum bile acid level was decreased in the high responders fed plant sterols but only when the diet contained the highest level of cholesterol. In both groups serum bile acid levels were not altered when cholesterol biosynthesis was inhibited by feeding triparanol. It is suggested that cholesterol feeding increases the serum bile acid level probably due to an increase in the intestinal pool of bile acids as a result of increased production of bile acids in the liver and their excretion into the bile. PMID- 1590674 TI - Use of immune modulators in nonspecific therapy of bacterial infections. PMID- 1590675 TI - Structure-activity relationships and mode of action of 5-mercapto-substituted oligo- and polynucleotides as antitemplates inhibiting replication of human immunodeficiency virus type 1. AB - Introduction of a reactive 5-mercapto group into some of the cytosine and/or uracil bases of various oligo- and polynucleotides by partial thiolation resulted in several potent inhibitors of the replication of human immunodeficiency virus type 1 (HIV-1) in primary human lymphocytes. These compounds exhibited little if any toxicity against uninfected peripheral blood mononuclear cells and showed 15 to 75 times higher antitemplate activity against a p66/p51 HIV-1 recombinant reverse transcriptase (RT) than against the DNA polymerase alpha from human lymphocytes. In contrast, the unthiolated oligo- and polynucleotides are void of antitemplate activity, and their apparent inhibitory effect on HIV-1 closely paralleled their toxicity for the cells. Partially thiolated poly(dC) (MPdC) was the most potent of all the compounds tested against HIV-1 in peripheral blood mononuclear cells (50% effective concentration, 1.8 micrograms/ml or 0.019 microM), while showing low cytotoxicity (greater than 100 micrograms/ml). The corresponding unmodified poly(dC) showed no anti-HIV-1 activity at 50 micrograms/ml but had pronounced cytotoxicity. MPdC was also a potent inhibitor of HIV-1 RT (50% inhibitory concentration, 0.30 micrograms/ml). The inhibitory activities of thiolated homooligo(dCs) against both HIV-1 replication and HIV-1 RT increased with increasing chain length. The heterooligonucleotides included in this study were designed as structural analogs of portions of the natural primer of HIV-1 RT, i.e., tRNA(3Lys). An 18-mer analog of the 3' terminus, complementary (antisense) to the primer-binding site of the HIV-1 genome, was attached to an oligo(dC) tail and 5-thiolated; this increased its activity and decreased its toxicity. This compound will serve as a new lead in the development of more effective antitemplates against HIV-1. PMID- 1590676 TI - Antimicrobial susceptibility changes in Enterococcus faecalis following various penicillin exposure regimens. AB - Penicillin-"virgin" strains of Enterococcus faecalis collected from a population of individuals with no previous antibiotic exposure were subjected in vitro to penicillin delivered as repeated pulses, stepwise increasing concentrations, or sustained levels of a single concentration. Changes in resistance to penicillin were assessed by determination of MICs, and time-kill studies were performed to evaluate changes in tolerance to the bactericidal effects of penicillin. Isogenic clones, derived from various exposure regimens, which exhibited changes in either resistance or tolerance were further examined for changes in penicillin-binding proteins. Exposure to repeated pulses of penicillin resulted in the development of tolerance to penicillin without changes in the level of resistance. Clones derived from a regimen of stepwise increases in the penicillin concentration acquired both increased penicillin resistance and tolerance. Clones selected after prolonged continuous exposure to a fixed concentration of penicillin displayed minimally increased resistance to penicillin, but they retained the lytic, nontolerant response to the bactericidal effect of penicillin. Clones which acquired tolerance to the bactericidal effect of penicillin without changes in penicillin resistance exhibited a penicillin-binding protein pattern identical to that of the parental strain. Increased labeling of several penicillin-binding proteins accompanied the development of increased penicillin resistance in both penicillin-tolerant and nontolerant strains. Exposure of E. faecalis to penicillin in repeated pulses of brief duration, for prolonged periods at a constant concentration, or in stepwise graded concentrations can result in the selection of clones with increased resistance to the inhibitory or bactericidal effects of penicillin, or both. These observations may be relevant to the selection of dosing regimes for penicillin in the treatment of enterococcal infections, when bactericidal synergism cannot be achieved with penicillin aminoglycoside combinations. PMID- 1590677 TI - Disposition of cefpodoxime proxetil in healthy volunteers and patients with impaired renal function. AB - The disposition of cefpodoxime in 24 subjects with various degrees of renal function after administration of a single oral dose of 200 mg of cefpodoxime proxetil (equivalent to 200 mg of cefpodoxime activity) was studied. Subjects were assigned to one of four groups (six per group): group I, normal renal function (creatinine clearance [CLCR], greater than ml/min); group II, mild renal impairment (CLCR, 50 to 80 ml/min); group III, moderate renal impairment (CLCR, 30 to 49 ml/min); or group IV, severe renal impairment (CLCR, 5 to 29 ml/min). Although cefpodoxime terminal elimination half-life in group I (2.55 +/- 0.25 h [mean +/- standard deviation]) was not significantly different from that in group II (3.53 +/- 0.74 h), the half-life values for group III (5.90 +/- 1.67 h) and group IV (9.80 +/- 1.21 h) were significantly prolonged compared with those of group I. The mean absorption rate constant was similar among groups and ranged from 0.68 to 0.85 h-1. All groups exhibited absorption lag-times which were comparable (0.30 to 0.41 h), and the apparent volume of distribution was similar among groups. Cefpodoxime apparent total body clearance (CLP/F) values in groups II, III, and IV (132 +/- 29, 112 +/- 41, and 55.7 +/- 9.9 ml/min, respectively) were significantly lower than that in group I (238 +/- 44 ml/min). Cefpodoxime CLP/F was positively correlated with CLCR (r2 = 0.79; P less than 0.05): CLP/F = (1.9 CLCR) + 18.4. Renal clearance also declined with decreasing renal function. Adjustments in cefpodoxime organism and on the site and severity of infection. Simulated plasma concentration-time data from this study suggest that 200 mg of cefpodoxime proxetil administered every 12 to 24 h to subjects with CLcr between 30 and 49 ml/min and 200-mg dose taken every 24 h by subjects with CLcr between 5 and 29 ml/min will maintain cefpodoxime concentration in plasma similar to those in subjects with normal renal function who receive a standard dosage mg every 12 h. PMID- 1590678 TI - Effect of an arginine-glycine-aspartic acid-containing peptide on hematogenous candidal infections in rabbits. AB - The adherence of Candida albicans yeast cells to the subendothelial extracellular matrix, fibronectin, laminin, and type I and IV collagen was tested. Fibronectin (10(-7) M) and a peptide, PepTite-2000 (Telios Pharmaceuticals Inc., San Diego, Calif.), containing the sequence arginine-glycine-aspartic acid (RGD) inhibited Candida adherence to these targets by greater than 90%. When C. albicans was perfused over ex vivo rabbit aortic endothelium, there was no significant difference in the amount of adherence in the presence or absence of the RGD containing peptide. However, the RGD-containing peptide reduced the number of Candida organisms present in liver, brain, heart, and kidneys (P less than 0.05) of rabbits 4 h after intravenous inoculation of 5 x 10(7) C. albicans yeast cells. The peptide also reduced the number of macroscopic Candida abscesses in the kidneys of rabbits 72 h after intravenous inoculation of 10(7) C. albicans yeast cells (P less than 0.05). Inhibition of Candida adherence in vitro and in vivo may occur because the peptide blocks a fungal receptor that is necessary for adherence. PMID- 1590679 TI - Ticarcillin and ticarcillin-clavulanic acid susceptibility tests: error rates for disk tests with consecutively isolated members of the family Enterobacteriaceae. AB - A five-laboratory coordinated study was undertaken to determine whether ticarcillin and ticarcillin-clavulanic acid disk susceptibility tests could accurately detect resistance among enteric bacilli. Each facility performed disk tests and broth microdilution susceptibility tests with reagents distributed from a common source, and appropriate controls were included in order to ensure methodologic uniformity. Each institution tested 500 consecutively isolated enteric bacilli against ticarcillin and ticarcillin-clavulanic acid. The prevalence of discrepancies between disk tests and dilution tests with 2,435 unselected enteric bacilli provided a valid estimate of the true error rate for tests with the two disks. The current interpretive criteria for susceptibility tests with ticarcillin and ticarcillin-clavulanic acid disks were found to be reliable; i.e., there were major or very major discrepancies between MIC categories and disk test results for less than 1% of all strains and minor discrepancies for only 5 to 10%. Even lower error rates would occur if the zone size-interpretive criteria were modified, but at this time it is difficult to determine whether the practical problems created by making such changes can be justified by the magnitude of the problem that is being resolved. PMID- 1590680 TI - Multiple-dose pharmacokinetics of cefprozil and its impact on intestinal flora of volunteers. AB - The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chromatography and bioassay. The pharmacokinetic parameters were calculated on the basis of an open one-compartment model. The mean maximum concentration in serum on day 1 was 11.5 +/- 2.6 mg/liter, and the time to reach maximum concentration was 122.3 +/- 30 min after administration. Bioavailability parameters (area under the concentration-time curve from zero to infinity, maximum concentration of the drug in serum, and urinary recovery) indicated an excellent absorption. No accumulation over the 8-day period was registered. Cefprozil had a short biological elimination half-life of 58 +/- 10 min and a renal clearance of 210 +/- 51 ml/min, indicating high rates of renal excretion and tubular secretion. Analysis of the fecal flora showed an ecological impact of cefprozil on the intestinal microflora, such as a moderate decrease in enterobacteria and a slight increase in enterococci, staphylococci, and bacteroides during the study. The number of all bacterial species was already normalized 4 days after the administration period. The tolerance of cefprozil proved to be excellent; only a slight and reversible increase of liver enzymes (in two volunteers), mild cephalalgia, tiredness, and soft stool were registered during the 8-day period. Cefprozil had excellent absorption, no accumulation over an 8-day period, and only a limited impact on the intestinal microflora. PMID- 1590681 TI - Efficacy of ciprofloxacin for treatment of Brucella melitensis infections. AB - The effectiveness of treatment of human brucellosis caused by Brucella melitensis with ciprofloxacin alone was investigated in a prospective nonrandomized study. Subjects with central nervous system involvement, endocarditis, or severe renal dysfunction; children under 16 years of age; and pregnant women were excluded from the study. Of 19 patients, 16 completed the study; 7 were diagnosed as having acute systemic brucellosis, and 9 had acute brucella arthritis-diskitis. A rapid response to ciprofloxacin was seen in all 16 patients, but the blood cultures of 1 patient remained positive and the treatment was changed. During a 104-week follow-up period, 4 of the 15 responding patients relapsed or were reinfected within 8 to 32 weeks after completion of therapy. We conclude that treatment with ciprofloxacin alone, although effective for the acute symptoms, is associated with an appreciable rate of relapse; therefore, it should be given with other agents for treatment of brucellosis. PMID- 1590682 TI - Multicenter prospective randomized trial comparing ceftazidime plus co trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis. AB - A prospective randomized trial was conducted at Srinagarind and Khon Kaen hospitals. Ceftazidime (100 mg/kg of body weight per day) and co-trimoxazole (trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) therapy was compared with conventional therapy (chloramphenicol, 100 mg/kg/day; doxycycline, 4 mg/kg/day; trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) in the treatment of 64 patients with bacteriologically confirmed cases of severe melioidosis who were admitted during September 1986 to January 1989. Of 61 evaluable patients (3 were excluded because of severe drug allergies), 42 were septicemic, and 31 of these patients had the most severe form, disseminated septicemic melioidosis. Their cumulative mortalities on day 7 were compared. There were significantly lower overall mortalities from melioidosis, septicemic melioidosis, and disseminated septicemic melioidosis in the group receiving the new treatment compared with those in the group receiving the conventional treatment (47 versus 18.5% [P = 0.039], 57.7 versus 25% [P = 0.039], and 82.3 versus 30.7% [P = 0.006], respectively); but the differences could have been influenced by the greater severity of illness, e.g., shock at initial presentation, in the patients who received the conventional treatment. Among patients with disseminated septicemia and initial shock, there was no significant difference in mortality between the regimens. Both regimens effectively eradicated bacteria from the circulation within 24 h (97 versus 96%, respectively). We recommend ceftazidime and co-trimoxazole as the drugs of choice for treatment of severe melioidosis, especially in those patients with disseminated septicemia. PMID- 1590683 TI - Role of metronidazole resistance in therapy of Helicobacter pylori infections. AB - Susceptibility to metronidazole was determined by disk diffusion tests for 559 strains of Helicobacter pylori isolated from patients. The overall metronidazole resistance was 26%. In males metronidazole-resistant strains made 18% of all H. pylori strains, and in females the corresponding figure was 40% (P less than 0.001). MICs of metronidazole were determined for H. pylori strains from 86 patients undertaking triple therapy, i.e., treatment with colloidal bismuth subcitrate, amoxicillin, and metronidazole. Of the nonresponders who remained culture positive despite the therapy, 69% had strains with metronidazole MICs of greater than or equal to 32 micrograms/ml before the therapy, and all nonresponders had metronidazole-resistant strains after the therapy. Metronidazole resistance was, however, also found in 27% of responders before therapy. To find whether the MICs of metronidazole for H. pylori strains remained constant for longer periods, consecutive isolates sampled several years apart from the same patients were tested in parallel and no changes in the MICs were found. H. pylori was successfully eradicated by the triple therapy from 91% of patients with metronidazole-susceptible pretreatment strains and from 63% of patients with metronidazole-resistant strains before the therapy (P less than 0.01). Although resistance to metronidazole has a significant role in treatment failures in H. pylori infections, high eradication rates can be achieved with the use of the present triple therapy even in populations with a high overall metronidazole resistance rate. PMID- 1590684 TI - Synergistic effects of romurtide and cefmenoxime against experimental Klebsiella pneumonia in mice. AB - We investigated the synergistic effects of romurtide (MDP-Lys [L18]) and cefmenoxime (CMX) in the treatment of experimental Klebsiella pneumonia in mice. Mice were infected with 1 x 10(4) CFU of Klebsiella pneumoniae by inhalation of aerosol bacterial suspension. About 90% of untreated animals died within a week; however, the mortality rate of animals treated with CMX alone at a dose of 40 mg/kg/day was 60% at 7 days after the infection. When one or two doses of L18 were administered before or after the infection concomitantly with CMX, a remarkable improvement in the survival rate was observed. There was no significant improvement in the survival rate of animals treated with L18 alone before or after infection. Histopathological sections of the lungs of mice treated with CMX and L18 showed slower progression of infection than those of mice treated with CMX alone. Significant differences were also found in quantitative cultures of viable bacteria in the lungs 1 to 4 days after the infection. Although viable bacterial counts in the lungs of the control and CMX treated groups showed a rapid increase 24 to 48 h after the infection, they remained lower than the initial counts (x 10(4)) in the lungs of mice treated with combination regimens. From these results, it can be concluded that L18 is a useful biological response modifier in the treatment of acute pulmonary bacterial infections. PMID- 1590685 TI - Effect of protein binding in serum on therapeutic efficacy of cephem antibiotics. AB - The effect of protein binding in serum of eight cephem antibiotics (ceftazidime, ceftizoxime, cefotiam, cefmetazole, cefpiramide, cefazolin, cefuzonam, ceftriaxone) on their therapeutic efficacies was examined in mice with experimentally induced intraperitoneal infections or pneumonia. The relationship among therapeutic activity, in vitro antibacterial activity, total or free (unbound) levels in serum, and homogenized whole lung levels was investigated. In the intraperitoneal infection caused by Staphylococcus aureus or Klebsiella pneumoniae, the 50% effective doses (ED50s) of the cephem antibiotics correlated with the area under the concentration-time curve (AUC) values of free levels in serum and the MICs but not with those of total levels in serum. A linear relationship was seen between 1/ED50 values and AUC of free levels in serum/MIC values. On the other hand, in mice with pneumonia caused by K. pneumoniae, the number of bacteria in the lung closely correlated with the AUC of the antibiotic concentration in lung tissue. There was a direct correlation between the levels in lung tissue and total levels in serum but not free levels in serum. The cephem antibiotics tested in this study were bound only slightly to homogenates of mouse lung. These results indicate that the effect of protein binding in serum on therapeutic efficacy against intraperitoneal infection differs from that against pulmonary infection. PMID- 1590686 TI - Double-blind randomized study of the effect of infusion rates on toxicity of amphotericin B. AB - Results of a double-blind randomized non-crossover study of rapid (45 min) versus slow (4 h) infusion of amphotericin B administered to 20 patients with proven or suspected fungal infection are reported. Toxicity was higher in the rapid infusion group than it was in the slow infusion group (mean total 7-day chill score, 173 +/- 276 versus 20 +/- 30 [P less than 0.01]; mean total 7-day dosage of meperidine required to abate rigors, 180 +/- 133 versus 58 +/- 78 mg [P less than 0.05]; and mean maximum total 7-day pulse rise, 225 +/- 64 versus 135 +/- 56 beats per min [P less than 0.02], respectively). When analyzed on a daily basis, the mean chill score, meperidine dosage, and pulse rise were also higher; and in addition, nausea and vomiting (5 of 11 patients who received a rapid infusion versus 0 of 9 patients who received a slow infusion [P less than 0.01]) appeared to be more common in those who received amphotericin B rapidly. The daily analysis approach proved that tolerance to these side effects developed with each subsequent infusion day, and by day 7 the incidence and severity were the same. This development of tolerance was significant for the mean chill score in the rapid infusion group (P less than 0.05) and for the proportion of patients with chills (P less than 0.005 for the slow infusion group; P less than 0.05 for the rapid infusion group). A decrease in creatinine clearance to greater than 51% of the baseline value was seen in two patients in each group. There were five deaths (four in the rapid infusion group, 1 in the slow infusion group) within 1 month, but none was clearly related to the amphotericin B infusion. The mean time to defervescence was similar for each group (10.8 +/- 4.1 days in the slow infusion group versus 9.9 +/- 5 days in the rapid infusion group). A rapid infusion regimen for amphotericin B cannot be recommended, at least during the first 5 to 7 days of treatment. PMID- 1590687 TI - Bactericidal activity of antimicrobial agents against slowly growing Helicobacter pylori. AB - The doubling times of bacteria at sites of colonization or infection are considerably longer than those in laboratory culture media, and slow growth reduces the susceptibility of bacteria to antimicrobial agents. Helicobacter pylori is susceptible to a wide range of antimicrobial agents in vitro; however, tests for inhibitory activity do not adequately predict which antimicrobial agents will eradicate slowly growing H. pylori from the stomachs of patients. The chemostat can be used to compare the bactericidal activities of antimicrobial substances against slowly growing bacteria. In this study we compared the bactericidal activities of antimicrobial agents against slowly growing H. pylori. The bactericidal activities of erythromycin, minocycline, ampicillin, amoxicillin, cefixime, metronidazole, and bismuth subcitrate against slowly growing H. pylori NCTC 11,637 in a chemostat were compared. Antimicrobial agents were added to the system at four to eight times the MIC. Exposure of H. pylori to metronidazole was associated with the rapid development of metronidazole resistance, preventing assessment of the bactericidal activity of metronidazole. Resistance to the other antimicrobial agents tested did not develop. The poor bactericidal activities of the antimicrobial agents against slowly growing H. pylori may be a contributory factor in limiting their clinical efficacies. Of the agents tested, only amoxicillin and bismuth subcitrate showed bactericidal activity against slowly growing H. pylori. The chemostat allows comparison of the bactericidal activities of antimicrobial agents against slowly growing H. pylori and may therefore provide results which more accurately identify those agents or combinations of agents that will eradicate H. pylori from patients. PMID- 1590688 TI - In vitro susceptibilities of the Bacteroides fragilis group to 14 antimicrobial agents in Korea. AB - The susceptibilities to 14 antimicrobial agents of 172 clinical isolates of the Bacteroides fragilis group from Korean patients during 1989 and 1990 were tested by an agar dilution method. All the isolates tested were susceptible to imipenem, chloramphenicol, and metronidazole. The rate of resistance to cefoxitin was 6%. PMID- 1590689 TI - Susceptibilities of anaerobic bacteria isolated from animals with ovine foot rot to 28 antimicrobial agents. AB - The agar dilution method was used to determine the inhibitory activities of 28 antimicrobial agents against 35 strains of the genus Peptostreptococcus, 4 strains of the species Peptococcus niger, 20 strains of the species Megasphaera elsdenii, 7 strains from the species Acidaminococcus fermentans, 8 strains of the genus Clostridium, 11 strains of the genus Eubacterium, and 1 strain of the species Propionibacterium acidipropionici, all of which were isolated from 125 clinical cases of ovine foot rot between January 1987 and December 1988. The three unreidopenicillins studied proved to be the most active antimicrobial agents, with a high percentage of strains being susceptible at a concentration of 64 micrograms/ml. Penicillin G, ampicillin, and the three cephalosporins studied also had good activity. Fosfomycin showed a high degree of activity among the 116 anaerobic bacteria tested. PMID- 1590690 TI - The separated enantiomers of 2'-deoxy-3'-thiacytidine (BCH 189) both inhibit human immunodeficiency virus replication in vitro. AB - Racemic 2'-deoxy-3'-thiacytidine (BCH 189) is a dideoxycytidine analog having a sulfur atom in place of the 3' carbon. The enantiomers of BCH 189 have been resolved and found to be equipotent in antiviral activity against human immunodeficiency virus types 1 and 2. However, the (-)-enantiomer (3TC) is considerably less cytotoxic than the (+)-enantiomer. PMID- 1590691 TI - In vitro activities of chloroquine in combination with chlorpromazine or prochlorperazine against isolates of Plasmodium falciparum. AB - The combinations of chloroquine plus chlorpromazine and chloroquine plus prochlorperazine were evaluated in vitro for potentiation against isolates of Plasmodium falciparum. Potentiation was observed against all chloroquine resistant isolates. There was no potentiation against 8 of 10 chloroquine susceptible isolates. The results indicated that the phenothiazines can potentiate chloroquine action against resistant parasites found in natural conditions. PMID- 1590692 TI - Comparison of SCH 39304 and its isomers, RR 42427 and SS 42426, for treatment of murine cryptococcal and coccidioidal meningitis. AB - SCH 39304 (304) and its isomers, SCH 42426 (426) and SCH 42427 (427), are new orally administered antifungal azole derivatives. In this study, we compared the efficacy of 304 with that of 426 and 427 in murine models of cryptococcal and coccidioidal meningitis. On day 18 postinfection with Cryptococcus neoformans, controls showed 80% mortality. The 50% protective doses calculated at this day were 0.56 mg of 304 per kg of body weight, 23.5 mg of 426 per kg, and 0.11 mg of 427 per kg. Controls with coccidioidal meningitis all succumbed, and treated mice at the same time point showed 50% protective doses of 10.8 mg/kg for 304, 200 mg/kg for 426, and 2.1 mg/kg for 427. We conclude that isomer 427 is five times as potent, whereas 426 is 1/50th as potent as 304 in these experimental mycoses. PMID- 1590693 TI - Effect of inoculum size on bacteriolytic activity of cefminox and four other beta lactam antibiotics against Escherichia coli. AB - MICs and turbidimetric experiments revealed a negligible inoculum effect with two Escherichia coli strains exposed to cefminox and cefoxitin, whereas a marked inoculum effect was revealed after exposure to cefotaxime, ceftizoxime, and imipenem. The activities of the cephamycins were associated with spheroplast formation and bacteriolysis at concentrations close to the MIC, whereas the other agents induced the formation of filaments or, in the case of imipenem, rounded cells. PMID- 1590694 TI - Intrahospital spread of a single gentamicin-resistant, beta-lactamase-producing strain of Enterococcus faecalis in Argentina. AB - Six beta-lactamase-producing (Bla+) isolates of Enterococcus faecalis recovered over a 17-month period from an Argentinian pediatric hospital were found to have identical or almost identical chromosomal restriction patterns by pulsed-field gel electrophoresis, although the plasmid patterns were different. These isolates, like Bla+ enterococci in the United States, hybridized to a staphylococcal Bla gene probe. The presence of a single strain was somewhat surprising, since all isolates transferred Bla by conjugation. PMID- 1590695 TI - In vitro evaluation of Ro 09-1227, a novel catechol-substituted cephalosporin. AB - Ro 09-1227 is a novel 7-position catechol-substituted parenteral cephalosporin that also has a 3-position radical similar to previously described cephems. The Ro 09-1227 spectrum was slightly wider than that of ceftazidime against members of the family Enterobacteriaceae tested, principally because of greater activity against species producing Richmond-Sykes type I beta-lactamases. Ro 09-1227 was also more active than ceftazidime against some strains producing extended spectrum plasmid-encoded beta-lactamases, such as TEM-3, -4, -5, -6, -7, and -9, SHV-2 and -3, and CAZ-2. Most strains of Pseudomonas aeruginosa, Xanthomonas maltophilia, and Acinetobacter spp. were also more susceptible to Ro 09-1227 than cefotaxime, ceftriaxone, cefoperazone, and ceftazidime. Haemophilus influenzae (MIC for 90% of strains tested [MIC90], 0.5 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml), and Moraxella (Branhamella) catarrhalis (MIC90, 0.5 micrograms/ml) were also Ro 09-1227 susceptible. Ro 09-1227 activity against important gram-positive cocci was most comparable to that of ceftazidime. Bacteroides fragilis (MIC90, greater than 32 micrograms/ml) and the enterococci (MIC90, greater than 32 micrograms/ml) were resistant to Ro 09-1227. These in vitro results indicate that this catechol-substituted cephalosporin may be useful as an empiric agent, especially for some isolates resistant to currently available broad-spectrum cephalosporins. PMID- 1590696 TI - Fleroxacin pharmacokinetics in aqueous and vitreous humors determined by using complete concentration-time data from individual rabbits. AB - Although composite data from separate subjects can be used to generate single subject estimates, intersubject variation precludes rigorous ocular pharmacokinetic analysis. Therefore, a rabbit model in which sequential aqueous and vitreous humor samples were obtained following the administration of the quinolone fleroxacin was developed. Mean data from individual animals were used for pharmacokinetic analysis. Following direct intravitreal or systemic drug administration, sequential paracenteses did not alter pharmacokinetic constants or ocular penetration and were not associated with an increase in ocular protein; contamination of vitreous humor with blood was minimal (less than 0.1%). Following direct injection or intravenous administration, vitreous humor concentration-time data were best described by one- and two-compartment models, respectively. The maximum concentration and the penetration into the aqueous and vitreous humors were 1.54 and 0.5 micrograms/ml and 27 and 10%, respectively. Elimination rates from aqueous and vitreous humors and serum were similar following parenteral drug administration. Drug elimination following direct injection was rapid, and the elimination rate from the vitreous humor was not prolonged by the coadministration of probenecid. Our animal model provides a new approach to the rigorous examination of the ocular pharmacokinetics of quinolone antimicrobial agents in the eye. PMID- 1590697 TI - Lipid complexing decreases amphotericin B inflammatory activation of human neutrophils compared with that of a desoxycholate-suspended preparation of amphotericin B (Fungizone). AB - Amphotericin B (AmB) has toxic effects and alters neutrophil (polymorphonuclear leukocyte [PMN]) function. A lipid-complexed formulation of AmB (AmB-LC) has been reported (A. S. Janoff, L. T. Boni, M. C. Popescu, S. R. Minchey, P. R. Cullis, T. D. Madden, T. Taraschi, S. M. Gruner, E. Shyamsunder, M. W. Tate, R. Mendelsohn, and D. Bonner, Proc. Natl. Acad. Sci. USA 85:6122-6126, 1988) to be less toxic than a desoxycholate-suspended preparation of AmB (AmB-des; Fungizone). In this study we compared the effects of AmB-des and AmB-LC on in vitro PMN function. Neither form of AmB stimulated PMN chemiluminescence, but AmB des (2 micrograms/ml) nearly tripled PMN chemiluminescence in response to f-Met Leu-Phe (fMLP), a phenomenon known as priming. Because AmB stimulates monocytes to release cytokines which can affect PMN function, we studied the effects of AmB on PMNs in mixed leukocyte cultures. AmB-des (1 to 2 micrograms/ml) increased the chemiluminescence of PMNs plus mixed mononuclear leukocytes (MNLs) to fMLP. The activity was about three times that of PMNs plus MNLs and seven times the activity of PMNs stimulated with fMLP in the absence of MNLs. Cell-free AmB-des (2 micrograms/ml)-stimulated, MNL-conditioned medium primed pure PMNs to a level equal to that of whole MNLs treated with AmB-des. AmB-LC was much less potent. AmB-LC (20 micrograms/ml) increased fMLP-stimulated chemiluminescence to two times that of PMNs plus MNLs without AmB-LC. AmB-des (2 micrograms/ml) (but not AmB-LC [2 micrograms/ml]) increased nitroblue tetrazolium reduction by PMNs in whole blood from 31 to 52% of positive cells. Neither form of AmB increased Mac-1 (the CD11b/CD18 integrin) expression of pure PMNs. AmB-des (0.5 to 2 micrograms/ml) (but not AmB-LC [< or = 40 micrograms/ml]) nearly doubled PMN Mac 1 expression in the presence of MNLs, and cell-free AmB-des (2 micrograms/ml) stimulated, MNL-conditioned medium stimulated PMN Mac-1 to 125% of the control level. AmB-des (0.2 to 2 micrograms/ml) (but not AmB-LC [< or = 40 micrograms/ml]) decreased chemotaxis of pure PMNs to fMLP by as much as 35% and that of PMNs in the presence of MNLs by as much as 50%. Desoxycholate by itself had no effect on PMN function. These differences in activity between AmB-des and AmB-LC may explain the lessened toxicity observed with AmB-LC. PMID- 1590698 TI - Comparative kill and growth rates determined with cefdinir and cefaclor and with Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae. AB - The relationship between the growth rate and the kill rate was used to evaluate and to compare the in vitro bactericidal activities of cefdinir, a new oral cephalosporin, and cefaclor against Streptococcus pneumoniae and beta-lactamase producing strains of Haemophilus influenzae. These frequently encountered pathogens of community-acquired respiratory tract infections are usually susceptible to both drugs. The MIC ranges for cefdinir and cefaclor were, respectively, 0.03 to 0.06 and 0.25 to 0.5 micrograms/ml for S. pneumoniae and 0.25 and 4 to 8 micrograms/ml for H. influenzae. The colony counts (CFU per milliliter) measured after 6 h of exposure to a range of antibiotic concentrations in broth were plotted against the colony count of the control culture over the same period of time. Higher kill rates versus bacterial growth rates were noted for S. pneumoniae for both drugs (positive balance). Conversely, lower kill rates versus growth rates were noted for H. influenzae for both drugs (negative balance). In conclusion, the bactericidal activities of both drugs against S. pneumoniae and H. influenzae were similar when expressed by the relationship between the growth rate and the kill rate at 6 h, but cefdinir was more active at lower concentrations. PMID- 1590699 TI - Use of radioactive ethanolamine incorporation into phospholipids to assess in vitro antimalarial activity by the semiautomated microdilution technique. AB - Phospholipid biosynthetic activity is intense in the erythrocytic stage of Plasmodium falciparum because of the parasite's own enzymatic machinery. The incorporation of various labeled phospholipid precursors in comparison with the incorporation of nucleic acid and protein precursors was tested to evaluate P. falciparum growth in vitro. These precursors, namely, [3H]ethanolamine, [3H]hypoxanthine, [3H]palmitate, [14C]serine, [3H]choline, [3H]inositol, and [3H]isoleucine, were all accurate indicators of parasite growth. However, because of its high level of incorporation, [3H]ethanolamine proved to be the best tool for assessing parasite viability. When culture parameters were carefully controlled, [3H]ethanolamine incorporation into phospholipids was proportional to pulse time, precursor concentration, and initial parasitemia and was sensitive to the number of uninfected erythrocytes (hematocrit). It can be used for a wide range of infected erythrocytes, from 2 x 10(4) to 5 x 10(5). The use of [3H]ethanolamine for in vitro antimalarial drug screening is a good alternative to the method of Desjardins et al. (R. E. Desjardins, C. J. Canfield, J. D. Haynes, and J. D. Chulay, Antimicrob. Agents. Chemother. 16:710-718, 1979). The major advantage is that the culture medium can be supplemented with hypoxanthine, which results in better parasite growth. [3H]ethanolamine is also an ideal tool when compounds that interfere with DNA and/or RNA metabolism are to be investigated for their effect on Plasmodium growth. PMID- 1590700 TI - Efficacy of cilofungin therapy administered by continuous intravenous infusion for experimental disseminated candidiasis in rabbits. AB - Cilofungin has potent in vitro activity against Candida albicans, but previous in vivo models using twice daily intermittent dosing regimens have not consistently demonstrated in vivo efficacy. Because of the pharmacokinetics of cilofungin in rabbits, it has been suggested that administration by continuous intravenous infusion might be more effective. We compared the in vivo efficacy of continuous intravenous infusion of cilofungin with that of amphotericin B in a rabbit model of disseminated candidiasis. Cilofungin prepared as previously described in phosphate-buffered 33% polyethylene glycol was lethal to infected rabbits in this model, as was phosphate-buffered 33% polyethylene glycol alone. In contrast, cilofungin in 26% polyethylene glycol and sterile water administered by continuous intravenous infusion was tolerated by rabbits, was significantly more effective than amphotericin therapy in reducing candida colony counts in kidney tissue, and was as effective as amphotericin therapy in lung and spleen tissue and in cardiac valvular vegetations. The dosage regimen and diluent used in some previous studies may have adversely affected outcome of treatment with cilofungin. PMID- 1590701 TI - Comparison of a polymerase chain reaction assay and a conventional microbiologic method for detection of methicillin-resistant Staphylococcus aureus. AB - The presence or absence of a methicillin resistance gene in 58 clinical isolates of Staphylococcus aureus was examined by the polymerase chain reaction (PCR) and Southern blot analyses. The results were analyzed in relation to those of the MIC assay of methicillin and oxacillin. PCR assay results were identical to those of Southern blot analysis of genomic DNA digested with HindIII (positive, 28 strains; negative, 30 strains). Among the 28 PCR-positive strains, 6 strains showed methicillin susceptibility by the conventional susceptibility test (MICs, less than or equal to 8 micrograms/ml). Culturing of the six strains with ceftizoxime led to an increase in the phenotypic level of resistance to methicillin and oxacillin, indicating that these strains should be classified as methicillin-resistant S. aureus (MRSA). The PCR assay was found to be a sensitive and reliable procedure for the rapid diagnosis of MRSA infection, even in cases in which the conventional MIC assay failed to detect MRSA. PMID- 1590702 TI - Comparison of SCH 39304, fluconazole, and ketoconazole for treatment of systemic infections in mice. AB - SCH 39304 was compared with fluconazole and ketoconazole in a systemic Candida albicans infection in mice (10(6) CFU per mouse). Results were based on survival rates and CFU in kidneys following once-daily oral treatment of 2, 5, or 10 days duration. In normal mice, SCH 39304 (dose to reduce kidney counts by 4 log units, 0.5 mg/kg of body weight) was 3 and 200 times more active than fluconazole and ketoconazole, respectively. In immunocompromised mice (gamma irradiation, 600 rads), SCH 39304 (dose to reduce kidney counts by 4 log units, 1.3 mg/kg) was 35 and greater than 100 times more active than fluconazole and ketoconazole, respectively. In normal mice, when the infecting inoculum varied from 10(5) to 10(7) CFU, only a fivefold increase in the dose to reduce kidney counts by 4 log units was observed with SCH 39304. Excellent protection was also seen when mice were treated with a single oral dose of SCH 39304 up to 24 h prior to infection with C. albicans. Studies in a systemic C. albicans infection model indicated that SCH 39304 is equally efficacious following either oral or intravenous administration. In a systemic Aspergillus flavus infection, mice treated with SCH 39304 (5 mg/kg) survived twice as long (16 days) as those treated with fluconazole (50 mg/kg) or controls did. PMID- 1590703 TI - Effects of recombinant human interleukin-6 alone and in combination with recombinant interleukin-1 alpha and tumor necrosis factor alpha on antibacterial resistance in mice. AB - In this study, recombinant human interleukin-6 (rIL-6) was tested for its ability to alter the resistance of mice to experimental Listeria monocytogenes infection. Single bolus or repeated injections of rIL-6 by itself did not increase antilisteria resistance. When rIL-6 was injected in combination with suboptimal concentrations of rIL-1 alpha and tumor necrosis factor alpha (rTNF-alpha), it did not augment their abilities to mediate protection in the spleen and had a marginal effect on the level of protection in the liver. Injection of rIL-6 together with protective doses of rIL-1 alpha did not diminish the protection stimulated by the latter. Unlike rIL-1 alpha and recombinant tumor necrosis factor alpha, rIL-6 appears to have little ability to elevate antibacterial resistance. PMID- 1590704 TI - High-level beta-lactamase activity in sputum samples from cystic fibrosis patients during antipseudomonal treatment. AB - The in vivo activity and source of beta-lactamase in sputum samples from 43 patients with cystic fibrosis (CF) during a 2-week antipseudomonal treatment were studied. A colorimetric method, based on the conversion of nitrocefin, was used for quantitation of the sputum beta-lactamase activity. beta-Lactamases in sputum were characterized by isoelectric focusing and inhibition profile and were compared with the beta-lactamases extracted from Pseudomonas aeruginosa isolated from the paired sputum samples. We found that the beta-lactamase activity increased to high levels in sputum from patients with CF during the course of piperacillin, ceftazidime, cefsulodin, or imipenem therapy. Aztreonam therapy lead to opposite results because the beta-lactamase activity decreased and aztreonam was able to mask beta-lactamase activity by acting as an inhibitor. All sputum beta-lactamases displayed characteristics indicative of a class I enzyme, identical to the beta-lactamases extracted from P. aeruginosa. The presence of beta-lactamase at such levels could lead to in vivo inactivation of beta-lactam antibiotics. This study supports the hypothesis that beta-lactamase production is an important in vivo resistance mechanism in P. aeruginosa-infected patients with CF. PMID- 1590705 TI - Five versus three days of ofloxacin therapy for traveler's diarrhea: a placebo controlled study. AB - In this double-blind study with 232 patients, 300 mg of ofloxacin given orally twice daily for 5 or 3 days was compared with placebo for the treatment of acute diarrhea in U.S. students visiting Guadalajara, Mexico. The 3-day regimen of ofloxacin was found to be as effective as the 5-day regimen in producing a clinical and microbiologic cure. Clinical cures for patients who received ofloxacin for 5 days occurred in 59 of 66 (89%) subjects, whereas clinical cure occurred in 77 of 81 (95%) of those who received ofloxacin for 3 days and in 56 of 79 (71%) of those who took placebo (P = 0.0001). When the duration of diarrhea after therapy was begun was compared in subgroups, a significant (P less than 0.05) shortening of posttreatment illness occurred in comparison with that in the placebo group for the following groups: for 5 days of ofloxacin, cases of shigellosis (32 versus 98 h); for 3 days of ofloxacin, all cases (28 versus 56 h), cases of enterotoxigenic Escherichia coli diarrhea (26 versus 66 h), cases of shigellosis (24 versus 98 h), all cases of illnesses associated with a bacterial enteropathogen (28 versus 69 h), and cases of illnesses in which numerous leukocytes were found in stool by microscopy (22 versus 49 h). Microbiologic eradication rates were 75 of 78 (96%) for patients who received ofloxacin and 37 of 46 (80%) for patients who received placebo (P = 0.009). There was no significant difference in the number of adverse events reported by patients in either of the treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590706 TI - Fusidic acid is highly active against extracellular and intracellular Mycobacterium leprae. AB - The activity of fusidic acid against Mycobacterium leprae was studied in axenic medium and in bacilli residing within mouse peritoneal macrophages. Activity was assessed by subsequent quantitation of bacillary radiorespirometric activity. Significant inhibition in both systems was observed at 0.156 micrograms/ml, and an approximately 50% reduction in activity occurred after exposure to 1.25 to 2.5 micrograms/ml. The excellent human pharmacokinetics and in vitro activity of fusidic acid against the leprosy bacillus warrant a clinical trial of this drug for leprosy. PMID- 1590707 TI - Construction of insertion mutants of Synechocystis sp. PCC 6803: evidence for an essential function of subunit IV of the cytochrome b6/f complex. AB - The gene encoding subunit IV of the cytochrome b6/f complex (petD) has been isolated from a genomic library of the unicellular cyanobacterium Synechocystis sp. PCC 6803. The coding region consists of 480 nucleotides and can code for a polypeptide with a molecular weight of 17.5 kDa. The deduced amino acid sequence shows high identity with the corresponding sequences of both the photoautotrophic prokaryote Nostoc sp. PCC 7906 as well as of lower and higher photoautotrophic eukaryotes (e.g. Chlorella prototecoides, Nicotiana tabacum). Transformation of Synechocystis sp. PCC 6803 with a plasmid containing the cloned petD gene in which the coding sequence is interrupted by the aminoglycoside 3' phosphotransferase gene (aph) from Tn903 resulted in the formation of km resistant transformants. The molecular analysis of independent transformants revealed that all clones were merodiploid containing both uninterrupted wild-type as well as interrupted mutant petD copies. Approaches to segregate these two genomes were unsuccessful implying an essential function of the petD gene product in Synechocystis sp. PCC 6803. PMID- 1590708 TI - Plasmid transformation of naturally competent Acinetobacter calcoaceticus in non sterile soil extract and groundwater. AB - The natural transformation of Acinetobacter calcoaceticus BD413 (trpE27) was characterized with respect to features that might be important for a possible gene transfer by extracellular DNA in natural environments. Transformation of competent cells with chromosomal DNA (marker trp+) occurred in aqueous solutions of single divalent cations. Uptake of DNA into the DNase I-resistant state but not the binding of DNA to cells was strongly stimulated by divalent cations. An increase of transformation of nearly 3 orders of magnitude was obtained as a response to the presence of 0.25 mM Ca2+. With CaCl2 solutions the transformation frequencies approached the highest values obtained under standard broth conditions, followed by MnCl2 and MgCl2. It is concluded that transformation requires divalent cations. DNA competition experiments showed that A. calcoaceticus does not discriminate between homologous and heterologous DNA. Furthermore, circular plasmid DNA competed with chromosomal DNA fragments and vice versa. The equally efficient transformation with plasmid pKT210 isolated from A. calcoaceticus or Escherichia coli indicated absence of DNA restriction in transformation. High efficiency plasmid transformation was obtained in samples of non-sterile natural groundwater and in non-sterile extracts of fresh and air dried soil. Heat-treatment (10 min, 80 degrees C) of the non-sterile liquid samples increased transformation only in the dried soil extract, probably by inactivation of DNases. The results presented suggest that competent cells of A. calcoaceticus can take up free high molecular weight DNA including plasmids of any source in natural environments such as soil, sediment or groundwater. PMID- 1590709 TI - Clinical trials and local treatment of early breast cancer. PMID- 1590710 TI - Cholesterol cysts of the petrous apex: radiological evaluation and surgical management. AB - The clinical presentation, diagnostic features and surgical management of three cases of giant cholesterol cysts involving the petrous apex of the temporal bone are presented. The ability to reach a confident pre-operative diagnosis using magnetic resonance imaging (MRI) due to its greater soft tissue contrast resolution, multiplanar imaging capabilities and sensitivity to blood products is illustrated. The operation of transmastoid infralabyrinthine draining of the petrous apex is described and other possible approaches discussed. PMID- 1590711 TI - Basal ganglia teratomas: report of three cases. AB - Three cases of intracranial teratomas occurring at the basal ganglia of three young male patients were reported. Their radiologic appearances closely resembled each other with multicystic tumor masses located deep in the basal ganglia. Histology showed teratocarcinoma, combined immature teratoma and germinoma, and teratoma with malignant transformation. These tumours represent a distinct clinico-radiologic group of lesions and serve as an addition to the dearth of information reported about the histological subtypes of intracranial teratomas. PMID- 1590712 TI - Postoperative seizures. AB - Two young patients with extensive ulcerative colitis were treated with oral steroids and developed seizures between 36 and 72 h after emergency colectomy. These cases highlight the problem of postoperative seizures, related to previous steroid administration, fluid overload, postoperative hypertension and biochemical abnormalities. PMID- 1590713 TI - Recurrent laryngeal nerve and the posterior fascial attachment of the thyroid gland. AB - An investigation based on dissection of cadaveric specimens was undertaken to obtain additional data on the relationships between the recurrent laryngeal nerve and the posterior fascial attachment of the thyroid gland. Ninety-four dissections were selected for detailed study. The posterior fascial attachment on each side was found to form two bands--a vertical band described previously and a horizontal band. The horizontal band was found to be present in all cases and to be constant in position. The posterior edge of the horizontal band followed posteriorly leads to the recurrent laryngeal nerve. The nerve always had a close relationship to the horizontal band and was often adherent to it. It is suggested that the use of the horizontal band to locate the recurrent laryngeal nerve would be of particular value when the inferior thyroid artery is absent, when the nerve is non-recurrent on the right side, or when there is distortion of the normal anatomy. PMID- 1590714 TI - Stereotactic fine needle biopsy of the breast. AB - The experience of the use of the TRC-Mammotest machine for stereotactic fine needle biopsy (SFNB) of the breast in Perth is presented. During the period 20 October 1988 to 10 January 1990, 404 SFNB were performed on 389 women with impalpable, mammographically detected lesions of the breast. Surgical biopsy was performed in 73 cases, of which 38 were malignant, giving a benign to malignant ratio in less than 1:1. The sensitivity for detecting cancer was 95%, with a positive predictive value of 100%. Using a combination of the mammographic and cytologic rating for the likelihood of cancer, all the cancers were detected and no cancers have developed in those considered mammographically and cytologically benign. The importance of a combined assessment of mammography and cytology in the management of patients with mammographically detected abnormalities is stressed. PMID- 1590715 TI - Colorectal cancer below age 40 in the Kingdom of Saudi Arabia. AB - This study compares colorectal cancer from the King Faisal Specialist Hospital and Research Center (KFSHRC) Tumour Registry in patients under and over 40 years and contrasts the data with registry data from New Zealand (NZ). Between 1975 and 1989 622 patients were registered at KFSHRC and 528 were Saudi. Three hundred and twenty-one were male and 207 were female. The average ages were 55.3 and 49.6. One hundred and nineteen were less than 40 years. More patients with proximal lesions were less than 40 years. Of the young patients 8.3% had small tumours (less than 4 cm) compared with 24.9% of patients over 40. Mucinous and signet ring carcinomata were more common in the young. Tumours were less well differentiated in younger patients. There were more young patients with 'localized' disease and nodal involvement. Older patients had more distant metastases. Of patients registered in NZ 5.5% were young compared with 23% of Saudi patients. In both countries localized disease was more common in the young. Nodal involvement was more frequently seen in the young in the Kingdom of Saudi Arabia (KSA) whereas the opposite was true in NZ. Distant metastases were more common in the old in the KSA but there were more young patients with metastases in NZ. In both countries young females with rectal tumours were more common but this ratio was reversed in the old. This study suggests that colorectal cancer may be more aggressive in the young in KSA but there was no evidence that the disease was more aggressive in young New Zealanders. Differences in the epidemiology of the disease in the young and old were found in both countries. PMID- 1590716 TI - Antimicrobial prophylaxis in patients undergoing abdominal surgery. PMID- 1590717 TI - Review of Swanson trapezium implants. AB - Sixteen Swanson trapezium silicone prostheses are reviewed retrospectively an average of 3 years after insertion. Fifteen were performed for osteo-arthritis and one for rheumatoid arthritis. Despite a very high patient satisfaction, 14 thumbs had residual functional compromise and caused pain when performing certain tasks. Three implants were completely dislocated and another four were significantly subluxed. One patient required implant removal. Intra-osseous cysts or significant bony erosion around the implant were present in five thumbs. It is concluded that there are early significant problems associated with this procedure which make it unsuitable for use in the osteo-arthritic thumb. PMID- 1590718 TI - Experimental calvarial growth disturbance by micro-plate and screw fixation. AB - A study was designed to help ascertain the effects of rigid internal fixation in the growing skull. Five piglets underwent plating of the left coronal suture at 3 weeks of age. At the time of surgery metal markers were placed to follow bone growth. Cephalometric radiographs, direct osteometry at sacrifice, gross pathological examination and specimen radiography revealed a localized disturbance of growth. There was a restriction of sutural displacement and appositional bone growth at the site of the plate. Local restriction of sutural growth was almost complete during the experimental period. There was an alteration to a 'mature' suture morphology, without synostosis, of the suture on the plated side not seen on the control side. A plagiocephalic pig was not produced nor was there an orbital deformity. A large local contour deformity developed and by the end of the experimental period the plate had become completely incorporated in bone. These effects were statistically significant as well as clinically significant. The clinical use of this type of fixation in reconstructive surgery of the infant craniofacial skeleton is questioned in light of the result. PMID- 1590719 TI - John Lockhart Gibson. During the Gallipoli Campaign 1915. PMID- 1590720 TI - Ileo-anal pouch procedure. PMID- 1590721 TI - Congenital pilonidal sinus of the nose. PMID- 1590722 TI - Endoscopic extraction of a calculous bile duct cast formed on a nidus of chromic catgut. PMID- 1590723 TI - Awareness of intermittent calf compressor injury in elderly people. PMID- 1590724 TI - Spontaneous bone graft resorption in os odontoideum. AB - Two children are presented who had posterior fusion of the upper cervical spine for os odontoideum. Both patients achieved radiographic fusion but spontaneous bone graft resorption occurred, resulting in a recurrence of the original instability. An awareness of this phenomenon, which has been rarely reported, is important in the pre-operative counselling and postoperative follow-up of these patients. PMID- 1590725 TI - Cubonavicular coalition: an unusual cause of peroneal spastic flat foot. AB - Cubonavicular coalition is a rare form of tarsal coalition which has only been previously described in an asymptomatic patient. A case is reported where this type of coalition caused symptoms of bilateral peroneal spastic flat feet. PMID- 1590726 TI - Arthroscopic removal of acrylic cement from unreduced hip prosthesis. AB - A case is reported in which entrapped polymethylmethacrylate following traumatic dislocation of a total hip replacement prevented complete reduction. A combined arthroscopic and fluoroscopic technique was used to remove the entrapped polymethylmethacrylate. Manipulation of the total hip prosthesis was done after removal of polymethylmethacrylate to minimize mechanical abrasion. This technique allows direct visual assessment of the articulating surfaces as well as the mechanical stability of the prosthesis. The morbidity related to the procedure is minimal and a short rehabilitation period is the major advantage. PMID- 1590727 TI - The staggerer gene curtails the reproductive life span of females. AB - Three studies were undertaken to investigate some features of the reproductive activity of female staggerer mice of the C57BL/6 strain. It was found that in the staggerer female, (1) vaginal opening and onset of vaginal estrous cycling were delayed; (2) the vaginal estrous cycle was irregular and characterized by abnormally prolonged diestrous and estrous phases, and (3) the reproductive life span of the mutant female was confined to a 3-month period after puberty. The abnormalities observed in sexual functions suggest a specific influence of the staggerer gene on reproductive activity. PMID- 1590728 TI - Asymmetric response to directional selection for licking behavior of Drosophila melanogaster males. AB - Selection for high and low licking rate was carried out on courting males of a cage-population of Drosophila melanogaster for 21 generations. The males were tested against a standard female tester genotype in every generation. The low scoring line responded linearly to selection, reaching a plateau after eight generations. The attempt to raise the licking rate above the level of the base population was not effective. The realized heritability of the L and H line over the first seven generations was 41.0 and 0.4%, respectively. From the fourth generation onward, the two lines differed significantly. Reciprocal crossing between the two lines indicated the absence of X-chromosome and maternal effects. There was no significant dominance. The selection for licking in males had no discernible effect on female sexual activity. H-line males mated significantly faster with standard females than L-line males. PMID- 1590729 TI - Coat color genes and cage temperature effects on care of the body surface (COBS) behavior of Meriones unguiculatus. AB - Male and female Mongolian gerbils (Meriones unguiculatus) carrying three coat color alleles, agouti, sandy, and black, were tested for 15 min under three cage temperature conditions, warm (35-40 degrees C), neutral (20 degrees C), and cold (0-5 degrees C). A frequency count of scratching, face and body wash, belly/side rubs, and shaking was taken of these animals' activities during the test sessions. Sex differences were not evident but coat color and age temperature affected the belly/side rubs and shaking activities. There were also effects of cage temperature but not coat color on face/body wash and scratching. It appears that animals with these coat color variants manifest disparate patterns of COBS behavior when encountering different thermal environments. PMID- 1590730 TI - Religion and education as mediators of attitudes: a multivariate analysis. AB - The transmission of social attitudes has been investigated as a possible model of cultural inheritance in a sample of 3810 twin pairs from the Australian National Health and Medical Research Twin Registry. Six social attitude factors were identified and univariate genetic models fitted to scores on each factor. A joint multivariate genetic analysis of the six attitude factors, church attendance, and education indicated that the attitudes were correlated--the same genes and shared environments influenced more than one attitude factor. A current controversy regarding social attitudes is whether the significant loadings on this shared environmental component represent true cultural influences or are actually the genetic consequences of phenotypic assortative mating for church attendance and educational attainment (Martin et al., 1986). In our data, church attendance is almost entirely due to the impact of the shared environment. The large shared environmental component on church attendance also accounts for a substantial part of the family resemblance in social attitudes, suggesting that not all of the apparent cultural effects found in earlier studies can be ascribed to the genetic effects of assortative mating. However, church attendance and education do not completely account for the cultural component. Therefore, effects in addition to church attendance, education, and assortative mating for church attendance and education must be involved in the cultural component of the inheritance of attitudes. PMID- 1590731 TI - Familial transmission of alcohol use: V. Drinking patterns among spouses, Tecumseh, Michigan. AB - This study examined concordance and discordance of self-reported alcohol consumption in 184 spouse pairs drawn from a representative sample of the Tecumseh, MI community. A significant association (tau B = .57, p less than .001) between self-reported alcohol consumption of husbands and that of wives was observed. Drinking daily and high maximum drinking were also significantly correlated between spouses, as were church attendance, smoking, impulsivity, and sociability. A significant association between the drinking of wives and that of their mothers-in-law was noted. The relationship between husbands' drinking and that of their fathers-in-law was marginally significant. However, three-quarters of daughters of heavy-drinking fathers (21 of 28) married abstemious men (never drank or drank lightly), while only 7% married heavy-drinking husbands. These findings lend support to the idea that a network of familial influences--both primary and secondary assortative mating--contributes to regulating adult drinking behavior. PMID- 1590732 TI - Single-locus control of saccharin intake in BXD/Ty recombinant inbred (RI) mice: some methodological implications for RI strain analysis. AB - The sac locus, with a major effect on saccharin preference, was discovered by Fuller (1974) in C57BL/6J (B6), DBA/2J (D2), and derived crosses, and is now supported in the BXD/Ty recombinant inbred (RI) series by a marked bimodal distribution in saccharin preference among 20 strains. The B6 allele led to increased saccharin preference compared to the D2 allele. Since the search for bimodal distributions reflecting major gene loci is an essential part of RI strain analysis, a new statistical method is proposed to test for bimodality, and comparisons are made to previously proposed methods. Another new RI method, quantitative trait loci (QTL) analysis, allows provisional detection and mapping of minor as well as major gene loci. Using this method as a screen, significant associations with saccharin preference were suggested with marker loci on portions of six chromosomes. One of these, the D12nyu1 locus on chromosome 12, was independently supported in a panel of standard (non-RI) inbred strains also tested for saccharin preference. It is unclear whether this reflects the sac locus. PMID- 1590733 TI - Hypertrophic cardiomyopathy: failure to demonstrate mutations in exon 13 of the cardiac beta myosin heavy-chain gene. AB - Familial hypertrophic cardiomyopathy (FHCM) has been linked to the cardiac beta myosin heavy-chain (MHC) genes on chromosome 14 (14q1), and a missense mutation within exon 13 of the beta MHC gene has been implicated in the pathogenesis of the disease. To test whether this constitutional mutation occurs somatically in the myocardium of the sporadic form of the disease, we studied seven patients with familial (n = 3) or sporadic (n = 4) hypertrophic cardiomyopathy (HCM). Amplification of exon 13 of the beta MHC from paraffin-embedded myocardium using the polymerase chain reaction (PCR) was performed and analysis of the amplified product for migration abnormalities using denaturing gradient gel electrophoresis (DGGE) and direct sequencing of the PCR product were used. Neither patients with HCM nor subjects with dilated cardiomyopathy (DCM) (n = 2) exhibited an aberration within exon 13 of the myocardial beta MHC. It is concluded that a specific beta MHC gene mutation is displayed only in a subset of patients with familial disease, thus further emphasizing the notion of genetic heterogeneity. In addition, in the sporadic form of the disease, somatically occurring mutations in this particular exon could not be demonstrated. PMID- 1590734 TI - Changes in phosphoinositide-specific phospholipase C and phospholipase A2 activity in ischemic and reperfused rat heart. AB - Phospholipid metabolism is altered during ischemia and post-ischemic reperfusion. Past studies demonstrating elevated myocardial free fatty acid and lysophospholipid content infer accelerated phospholipid degradation involving phospholipase A activity. Recently, ischemic and post-ischemic reperfusion (reperfusion) have been shown to affect levels of phosphoinositide (PPI) degradation products. Considering the role of PPI turnover in regulation of cellular calcium homeostasis, our laboratory and others have suggested that alteration in the metabolism of the inositol phospholipids could play a role in the development of ischemia-induced calcium overload injury. Using an isolated rat heart model (Langendorff perfusion), this study examines the effect of global ischemia and reperfusion on ventricular phosphoinositide-specific phospholipase C (PLC) activity and PLA2 activity. The primary purpose was to determine if ischemia and reperfusion-induced changes in PLC activity could explain previously observed changes in PPI degradation products, and whether PLC and PLA2 activities were similarly or differentially altered by ischemia and reperfusion. PLC and PLA2 activities were measured in cytosolic and total membrane fractions from control (perfused), ischemic (5, 10, 30, and 60 min), and post-ischemic reperfused ventricular tissue. Phospholipase activity was determined under optimal in vitro conditions using exogenous radiolabeled substrates. Alterations in membrane-associated PPI-PLC activity correlated with reported ischemia and reperfusion-induced changes in ventricular content of PPI metabolites. Membrane PLC activity increased slightly at 5 min of ischemia, decreased significantly at 10 min of ischemia, and continued to decrease with longer duration of ischemia (73% of control after 60 min). Cytosolic PPI-PLC activity was decreased at 5 min, and then significantly increased by longer durations of ischemia, while cytosolic PLA2 activity was reduced at all time points. Pretreatment with muscarinic, alpha 1-adrenergic, beta-adrenergic, and adenosine receptor blockers did not alter ischemia-elicited changes in PLC activity. Reperfusion caused a 140% to 200% rise in the activities of all phospholipases in all fractions after 40 min of ischemia, but not after 10 min of ischemia. Results suggest 1) ischemia and reperfusion-elicited alterations in membrane-associated PPI-PLC activity can explain previously observed changes in phosphoinositide turnover metabolites, 2) cytosolic and membrane-associated PPI-PLC and PLA2 activities are not uniformly affected by ischemia, 3) reperfusion following ischemia of sufficient duration initiates uniform activation of PIP2-PLC and PLA2, and 4) because ischemia and reperfusion-induced changes in phospholipase activity can be detected under optimal in vitro assay conditions (removed from the in vivo ischemic microenvironment), it is likely that the enzymes themselves have been altered. PMID- 1590735 TI - Preconditioning of the heart by repeated stunning: attenuation of post-ischemic dysfunction. AB - The effect of repetitive brief periods of coronary occlusion on subsequent prolonged ischemic insult was studied using a swine heart model. Four 5-min episodes of left anterior descending coronary artery (LAD) occlusion, each separated by 10 min of reperfusion, did not affect any of the regional or global myocardial functions examined, except that the level of adenosine triphosphate (ATP) dropped to some extent. Sixty minutes of LAD occlusion following four repeated stunnings further reduced the ATP level, but this reduction was significantly lower compared to nonstunned control. Myocardial global functions were not affected significantly by prolonged ischemic insult. Segment shortening (SS) was reduced comparably in both control and stunned groups. However, SS improved significantly during subsequent reperfusion in the stunned group compared to control. The experimental group also demonstrated reduced infarct size and an area of risk compared to nonstunned control. These results indicate that repeated stunning prior to irreversible ischemic insult can attenuate ischemic injury and post-ischemic dysfunction. PMID- 1590736 TI - Adrenergic stimulation of rat hearts with severely reduced cytosolic adenine nucleotide pool and [ATP]/[ADP]ratio. AB - The effect of severe reduction of cytosolic adenine nucleotide (AdN) pool and [ATP]/[ADP] ratio (by 2-deoxyglucose treatment) on functional and metabolic responses of isovolumic rat heart to increased energy demand induced by coronary flow (CF) rise and isoproterenol (Iso) addition has been investigated. AdN depleted hearts had reduced phosphocreatine (PCr, by 80%), ATP (by 75%), [ATP]/[ADP] (24 times) and pressure-rate product (PRP, by 60%). An elevation of CF was followed by the increase in PRP in control and AdN-depleted hearts by 40 45% with unchanged metabolic parameters. At increased CF, Iso caused a further rise in PRP in both groups due to elevation of heart rate; however maximal levels of PRP in the AdN-depleted group still remained lower than that of control (by 40%). Only in control experiments was Iso addition accompanied by an increase in the difference between left-ventricular end- and minimal diastolic pressure, cytosolic [Pi] and [ADP], and some decrease in PCr and [ATP]/[ADP]. These data imply that severely reduced cytosolic [ATP]/[ADP] does not prevent acceleration of Ca2+ turnover by Iso in cardiomyocytes, it but restricts maximal force development affecting the myofibrils. PMID- 1590737 TI - Oxygen free radical damage of isolated cardiomyocytes: comparative protective effect of radical scavengers and calcium antagonists. AB - Oxygen free radicals have been shown to play a major role in the development of perfusion abnormalities, contractile dysfunction, and irreversible injury in ischemic-reperfused myocardium. The aim of this study was to assess the direct protective effects of radical scavengers, calcium antagonists, and combination of these substances against free radical induced myocyte damage. Viability (% of rod shaped cells) and adenine nucleotide content (AdN, high-pressure liquid chromatography) of isolated adult rat cardiomyocytes were measured after exposure to hypoxanthine (2 mM) and xanthine oxidase (25 mU/ml). After 90 min, viability of myocytes decreased to 4.2 +/- 3.4% (mean +/- SEM) of pre-exposure control, and AdN decreased from 28.2 +/- 1.8 to 8.09 +/- 1.1 nmol/mg protein. Addition of catalase (1500 U/ml) resulted in the preservation of viability (77 +/- 6% of pre exposure control, n = 6, mean +/- SEM), and AdN 84 +/- 6%, p less than 0.001. These values are not significantly different from those measured in myocytes not exposed to free radicals (88 +/- 9% and 79 +/- 6%, respectively). Superoxide dismutase (2400 U/ml), dimethylthiourea (10 mM), and desferrioxamine (1 mM) did not preserve either viability or AdN. The calcium antagonist verapamil (10 microM) also preserved myocyte viability significantly (23 +/- 9.7%, p less than 0.05 vs unprotected cells), but failed to prevent the loss of AdN (13.2 +/- 4%, not significant as compared to unprotected cells). Viability and AdN in myocytes treated with nifedipine (10 microM) or diltiazem (10 microM) were not higher than in unprotected cells. All combined treatment forms which included catalase resulted in the preservation of myocyte viability as well as AdN. These data show that only the hydrogen peroxide scavenger catalase protects isolated cardiomyocytes against free radicals generated in the purine catabolic pathway. PMID- 1590738 TI - Tolerance of myocardium of aged animals to repeated oxygen deficiency. AB - Hemodynamic and metabolic effects of three times 4 min of oxygen deficiency were investigated in 18-month-old rats in comparison to 4-month-old Wistar rats. Left ventricular isovolumic-pressure-generating capacity and dp/dtmax during isovolumic conditions and hemodynamic indices during intact circulation were determined in open-chest rats. Additionally, high-energy phosphates were measured at the end of the experiments after 20 min of postasphyxial recovery. Older rats had a significantly reduced isovolumic left-ventricular pressure generating capacity (236 +/- 9 vs 269 +/- 5 mm Hg; p less than 0.05) and a low cardiac index (55 +/- 9 vs 117 +/- 8 ml x min-1 x kg-1). The effects of the oxygen deficiency were comparable in both groups. The isovolumic pressure generating capacity was reduced for 11% vs 14%, and dp/dtmax for 13% vs 13%. The myocardial ATP-content was also decreased for the same extent in both groups (0.6 vs 1.0 mumol/gww). Both hemodynamic and biochemical results indicate that aged myocardium does not have a reduced tolerance to repeated periods of oxygen deficiency. PMID- 1590739 TI - Effects of adriamycin on chronic cardiotoxicity in selenium-deficient rats. AB - Adriamycin (doxorubicin) is an antineoplastic drug used to treat various cancers; however, its chronic use is unfortunately accompanied by cardiotoxicity. This toxicity can be reduced by antioxidant agents such as selenium, and it is particularly interesting that cancer patients are usually deficient in this trace element, which suggests that its supplementation could contribute to beneficial treatment. We have examined the effect of adriamycin on chronic cardiotoxicity in 6-week selenium deficiency in rats. Selenium-deficient rats showed a considerable reduction of selenium levels and of selenium-containing glutathione peroxidase. Cardiac lipid peroxides increased slightly in the deficient rats, whereas plasma and heart lipid peroxides increased markedly in adriamycin-treated rats. This increase was greatly accentuated in selenium deficiency. These results suggest that free radical mechanism may be contributing to adriamycin toxicity, and above all show the importance of balancing the selenium levels in adriamycin-treated subjects to limit its harmful myocardial action. A decrease in adriamycin cardiotoxicity with no concomitant decrease in its antineoplastic activity would be of considerable value by improving the therapeutic benefit of the drug. PMID- 1590740 TI - Alanine, glutamate, and ammonia exchanges in acutely ischemic swine myocardium. AB - Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27 +/- 0.16 to 0.25 +/- 0.09 (ml/g)/min, and left ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p less than 0.05) and a switch to net lactate production (p less than 0.01). Ischemia did not affect the rates of alanine output (-0.9 +/- 1.0 vs. -0.3 +/- 0.3 mumol/min) or glutamate uptake (-0.4 +/- 1.1 vs. 0.3 +/- 0.6 mumol/min), but did increase the venous arterial difference for ammonia (-4.1 +/- 4.1 to 52.7 +/- 5.5 microM, p less than 0.0001) and the ammonia output (-0.33 +/- 0.24 to 1.34 +/- 0.14 mumol/min, p less than 0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism. PMID- 1590741 TI - High-frequency and low-frequency heart-rate fluctuation analysis in newborns--a review of possibilities and limitations. AB - Respiratory sinus arrhythmia (RSA) has been traditionally defined as the high frequency component of heart-rate fluctuations (HRF) synchronous with the respiratory movements (RM), i.e., the frequency of RSA corresponds to the respiration rate. It can be shown that at defined relations of mean heart and respiration rate some essential effects must be taken into consideration in studies using RSA parameters. The relevance of these effects is shown and a new strategy of RSA quantification demanded, at least in neonates. The diagnostic importance, physiological background and future application of the low-frequency components of the neonatal HRF are reviewed on the basis of our own results. Nonrespiratory cardiovascular HRF cannot always be detected in the neonate by power spectral analysis. Movement-related HRF have a potential diagnostic importance per se, but may also artefactually disturb the quantification of other HRF components. Long-term trends can be used to describe sleep-state related trends and their disturbances. PMID- 1590742 TI - Insulin resistance, hyperinsulinemia, and cardiovascular disease. The need for novel dietary prevention strategies. AB - Insulin resistance associated with hyperinsulinemia (metabolic syndrome) emerged in recent years as an important health risk which is present in approximately 25% of the normal population in western industrialized societies. Insulin resistance as assessed for the whole body arises from a reduced glucose utilization of skeletal muscle. If the metabolic syndrome persists over a prolonged period of time, detrimental influences on the cardiovascular system become apparent involving diabetes mellitus, hypertension, and arteriosclerosis. Of particular pathogenic relevance is an unbalanced influence of insulin arising either from a diminished or enhanced insulin action depending on whether the various tissues of the body exhibit a reduced or unchanged insulin sensitivity. Since insulin resistance and hyperinsulinemia appear to be affected by various lifestyle factors, the unique opportunity exists of reducing cardiovascular mortality by correcting this syndrome at a time when degenerative changes have not occurred in the cardiovascular system. Of great importance is the finding that dietary factors can have a modulatory action on insulin sensitivity. In animal experiments, an increased intake of (saturated) fat and refined carbohydrates increased insulin resistance. Since psychosocial distress is expected to be associated with a sustained activation of the sympathoadrenal axis, it is likely also to aggravate the metabolic syndrome. A factor with a beneficial action appears to be physical exercise. In view of the high incidence of cardiovascular diseases, further research on lifestyle factors with an insulin-sensitizing or insulin-desensitizing action is required. Of prime importance is the reevaluation of established dietary recommendations and diets should be designed which take into account the individual cardiovascular risk factor profile. PMID- 1590743 TI - Glucose-6-phosphate dehydrogenase deficiency and sulfadimidin acetylation phenotypes in Egyptian oases. AB - Screening of 1315 males from two Egyptian oases for glucose-6-phosphate dehydrogenase deficiency (G-6PD) found an incidence of 5.9%. The rate of acetylation of sulfadimidin was also studied, and a bimodal distribution was found with 73% rapid acetylators. There is a correlation between high frequency of G-6PD deficiency and high frequency of slow acetylation rate. PMID- 1590744 TI - Genetics of the hemolymph esterases of Lucilia cuprina (Diptera: Calliphoridae). AB - When hemolymph from adults of Lucilia cuprina was partitioned on native polyacrylamide gels, nonspecific esterase staining demonstrated 10 bands with up to six bands in an individual. The bands derive from alleles at two loci, EHA (five alleles) and EHB (four alleles). EHA is located on chromosome 4, 16.3 map units from sv (singed vibrissae) and 22.1 map units from ra (radial vein gaps). EHB is located on chromosome 5, 34.0 map units from to2 (topaz2 eyes) and 7.2 map units from mv (M1-veinless). PMID- 1590745 TI - alpha-L-fucosidase in human fibroblasts. I. The enzyme activity polymorphism. AB - Low plasma alpha-L-fucosidase activity is a recessive polymorphic trait observed in 8% of the normal population. The molecular basis of this polymorphism remains unclear and its expression is tissue specific. As the low-activity (variant) phenotype is expressed in vitro in cultured human fibroblasts, this cell type was chosen to study the enzyme activity polymorphism. Fibroblast cell lines derived from individuals with low plasma fucosidase activity (variants) have less than 30% of the fucosidase activity of fibroblast cell lines established from individuals with high plasma fucosidase activity (nonvariants). No qualitative differences in the synthesis, processing, and extracellular release of newly made alpha-L-fucosidase could be demonstrated among variant and nonvariant cell strains. Cells pulsed with 3H-leucine for 10 min produce a 51-kDa protein which is rapidly processed to a 55-kDa intermediate. The latter is converted to a mature 59-kDa intracellular and a 61-kDa extracellular end product, in both variant and nonvariant fibroblast cell lines. Variant and nonvariant fibroblast cell lines also release relatively equal amounts of fucosidase into the extracellular medium. Therefore, differences in processing or extracellular release of fucosidase between variants and nonvariants are not the basic mechanism of this tissue-specific activity polymorphism. PMID- 1590746 TI - Distribution of specific apolipoproteins determined by immunoblotting of baboon lipoproteins resolved by polyacrylamide gradient gel electrophoresis. AB - A method for the quantitative assessment of apolipoprotein distributions among baboon serum lipoproteins is described. The method combines the precise and reproducible separation of lipoproteins by polyacrylamide gradient gel electrophoresis with the specificity of immunoblotting. The method permits the measurement of distributions for any apolipoprotein for which there are antibodies available. Radioactive secondary antibodies are used to expose X-ray film, and distributions are determined by densitometry. Absorbance is linearly related to both antigen and antibody concentrations. The method is reproducible, with the mean coefficient of variation calculated to be 0.118, and has a high repeatability (r2 = 0.97). The immunoblotting method can be employed to measure the fine details of lipoprotein phenotypes as they are influenced by genotype and environment. PMID- 1590747 TI - Polymorphism in a Drosophila indirect flight muscle-specific tropomyosin isozyme does not affect flight ability. AB - We describe polymorphism in a Drosophila indirect flight muscle-specific tropomyosin isozyme, named TnH-34. Three variants of this protein differ in their mobilities as determined by 1-D and 2-D SDS-PAGE. Meiotic mapping places the polymorphism close to, if not within, the structural gene encoding this tropomyosin isozyme. The most likely site of the mutations is within a single C terminal exon. Flight-testing of different genotypes reveals that this variation in TnH-34 does not affect flight ability. These results suggest that some sequence variation may be tolerated in this section of the protein and correlate with the variability of this protein in different insect species. PMID- 1590748 TI - Restriction site variation, gene duplication, and the activity of sn-glycerol-3 phosphate dehydrogenase in Drosophila melanogaster. AB - Restriction site variation in a 25-kb region including the sn-glycerol-3 phosphate dehydrogenase (Gpdh) locus has been assessed in 29 single female D. melanogaster lines from the Cardwell (Australia, QLD) population. The Gpdh locus was duplicated in about one-third of the lines, although the duplication was incomplete and lacked exons 1 and 2. There was no restriction site variation in the duplicated region. Three insertions were found in the gene region but only one affected GPDH activity. The lines with the duplication had higher levels of GPDH activity and protein amount than did nonduplicated lines. This effect was also observed in lines extracted from two other Australian populations. The duplication is shown to have a similar structure in each population investigated and is also present in populations from China and Africa. It is suggested that the effect of the duplication on GPDH activity, which might be due to structural factors affecting transcription at the Gpdh locus, could account for the worldwide distribution of the duplication. PMID- 1590749 TI - Genetic variation at enzyme loci in North Atlantic minke whales, Balaenoptera acutorostrata. AB - Electrophoretic variation within and between North Atlantic minke whale samples (Balaenoptera acutorostrata) from West Greenland, Iceland, and Norway was investigated. In the West Greenland samples, 28 enzyme systems were examined, representing 36 loci, of which 6 were found to be polymorphic. In Icelandic and Norwegian samples, 22 enzyme systems were examined, representing 29 loci, of which 6 and 5 were found to be polymorphic, respectively. The average heterozygosity was 0.058 (SE = 0.024) in samples from West Greenland, 0.074 (SE = 0.028) in samples from Iceland, and 0.054 (SE = 0.023) in samples from Norway. No significant deviations from the expected Hardy-Weinberg genotypic frequencies, within samples taken from the same area, were found. Significant differences in allele frequencies were observed, however, between samples from the three different areas. The average Nei's genetic distance was 0.014 and the average Fst value was 0.126. The genetic differences between the samples from the different areas indicate that those from West Greenland, Iceland, and Norway represented different breeding populations. PMID- 1590750 TI - Genetic polymorphism and activities of human lung alcohol and aldehyde dehydrogenases: implications for ethanol metabolism and cytotoxicity. AB - Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) exhibit genetic polymorphism and tissue specificity. ADH and ALDH isozyme phenotypes from 39 surgical Chinese lung specimens were identified by agarose isoelectric focusing. The identity of the lung beta-ADHs was further demonstrated by their characteristic pH-activity profiles for ethanol oxidation, Km values for NAD and ethanol, and inhibition by 4-methylpyrazole or 1,10-phenanthroline. The beta 2 allele, coding for beta 2 polypeptide, was found to be predominant in the lung specimens studied. The ADH activities in the lungs with the homozygous phenotype ADH2 2-2 (exhibiting beta 2 beta 2) and ADH2 1-1 (exhibiting beta 1 beta 1) and the heterozygous phenotype ADH2 2-1 (exhibiting beta 2 beta 2, beta 2 beta 1, and beta 1 beta 1) were determined to be 999 +/- 77, 48 +/- 17, and 494 +/- 61 nmol/min/g tissue, respectively. Fifty-one percent of the specimens studied lacked the ALDH2 activity band on the isoelectric focusing gels. The activities in the lung tissues with the ALDH2-active phenotype and the inactive phenotype were determined to be 30 +/- 3 and 17 +/- 1 nmol/min/g tissue, respectively. These findings indicate that human pulmonary ethanol-metabolizing activities differ significantly with respect to genetic polymorphism at both the ADH2 and the ALDH2 loci. The results suggest that individuals with high Vmax beta 2-ADH and deficient in low-Km mitochondrial ALDH2, accounting for approximately 45% of the Chinese population, may end up with acetaldehyde accumulation during alcohol consumption, rendering them vulnerable to tissue injury caused by this highly reactive and toxic metabolite. PMID- 1590752 TI - Prolyl endopeptidase catalysis. A physical rather than a chemical step is rate limiting. AB - Prolyl endopeptidase represents a new family of serine proteases, and it has a mechanistic feature distinct from that of the enzymes of the extensively studied chymotrypsin and subtilisin families. The rate-determining step in the catalysis of serine proteases is a general base/acid-catalysed chemical step. For prolyl endopeptidase, however, the chemical step is not rate-limiting, as demonstrated by using substrates with different leaving groups. It is known that the acylation of chymotrypsin and subtilisin proceeds faster by several orders of magnitude with the activated nitrophenyl ester than with the corresponding amide substrates. In contrast, for the acylation of prolyl endopeptidase similar rate constants were obtained with nitrophenyl ester and several amide substrates. This result, combined with kinetic isotope studies [Polgar (1991) Eur. J. Biochem. 197, 441-447], offers strong evidence that a physical step, presumably a conformational change associated with substrate binding, is the rate-determining step in the prolyl endopeptidase catalysis. PMID- 1590751 TI - Characterization of functional human erythrocyte-type glucose transporter (GLUT1) expressed in insect cells using a recombinant baculovirus. AB - The human erythrocyte-type glucose transporter (GLUT1) has been abundantly expressed in insect cells by using a recombinant baculovirus. At 4 days after infection with the virus, the insect cell-surface and intracellular membranes were found to contain greater than 200 pmol of D-glucose-sensitive binding sites for the transport inhibitor cytochalasin B per mg of protein. The characteristics of binding were identical with those of the erythrocyte transporter, although the two proteins differed substantially in apparent Mr, probably as a result of glycosylation differences. PMID- 1590753 TI - Inhibition of bacterial protein synthesis by elongation-factor-Tu-binding antibiotics MDL 62,879 and efrotomycin. AB - MDL 62,879 (formerly GE 2270 A) is a novel antibiotic active against Gram positive bacteria by inhibiting protein synthesis. MDL 62,879 is not active against Gram-negative bacteria, but inhibits cell-free protein synthesis in extracts from Escherichia coli, and shows a high binding affinity for its elongation factor Tu (EF-Tu). We prepared ribosomes and protein-synthesis elongation factors from three sources: E. coli, Bacillus subtilis, and a strain of B. subtilis selected for resistance to MDL 62,879 (strain G1674). Homologous and heterologous reconstituted systems were used to compare the effects of MDL 62,879 and of efrotomycin, an EF-Tu inhibitor of the kirromycin class, which is inactive against both B. subtilis and E. coli. We showed that in cell-free protein synthesis: (a) E. coli was sensitive to both MDL 62,879 and efrotomycin; (b) B. subtilis was sensitive to MDL 62,879, but not to efrotomycin; (c) B. subtilis G1674 was resistant to both antibiotics. In the E. coli system and in the system from wild-type B. subtilis, inhibition by MDL 62,879 was reversed upon addition of purified EF-Tu from B. subtilis G1674. This demonstrates that the antibiotic acts by inhibition of EF-Tu. In contrast, extracts from B. subtilis failed to restore activity in an efrotomycin-inhibited E. coli system. Dominance or resistance to MDL 62,879 and of sensitivity to efrotomycin in heterologous cell-free protein synthesis confirms that inhibition of EF-Tu by the two antibiotics is mediated by different mechanisms of action. PMID- 1590754 TI - New kinetic parameters for rat liver arginase measured at near-physiological steady-state concentrations of arginine and Mn2+. AB - A cytosolic cell-free system from rat liver containing the last three enzymes of the urea cycle, a number of cofactors and the substrates aspartate and citrulline was shown to synthesize urea at near-physiological rates ranging between 0.40 and 1.25 mumol/min per g of liver. This system was used to determine the kinetic parameters for arginase. With saturating amounts of Mn2+ (30 microM), arginine remained at a steady-state concentration of 5-35 microM depending on the aspartate and citrulline supply. Vmax. at micromolar arginine concentrations was between 1.10 and 1.25 mumol/min per g of liver, the K0.5 (arginine) between 6.0 and 6.5 microM and positive co-operativity was observed (Hill coefficient 2). Omission of Mn2+ caused a significant accumulation of arginine during the incubation, suggesting a regulatory effect of arginase. Under these conditions, Vmax. was 1.10-1.65 mumol/min per g of liver and the Km (arginine) increased up to 14.4-21.1 microM. The apparent Ka for Mn2+ in the presence of physiological concentrations of ATP, Mg2+ and arginine was calculated to be maximally 8 microM. Initial-velocity experiments with millimolar arginine concentrations as the direct substrate gave the following results, which are in good agreement with literature data. In the absence of Mn2+, Vmax. was 71.3 mumol/min per g of liver and the Km (arginine) 1.58 mM. With 30 microM-Mn2+, Vmax. was 69.4 mumol/min per g of liver and the Km (arginine) decreased to 0.94 mM. On the basis of our results, we propose the presence of high-affinity and low-affinity sites for arginine on rat liver arginase and postulate that alterations in arginase activity arising from changes in the concentration of arginine and of the cofactor Mn2+ may contribute to the regulation of ureagenesis in vivo. PMID- 1590755 TI - Antizyme, a protein induced by polyamines, accelerates the degradation of ornithine decarboxylase in Chinese-hamster ovary-cell extracts. AB - Ornithine decarboxylase (ODC), the key regulatory enzyme for polyamine biosynthesis, is known to have a short intracellular half-life, and antizyme, an ODC-binding protein induced by polyamines, has been suggested to be involved in the process of ODC degradation. In the present study we demonstrated that antizyme markedly accelerated ATP-dependent degradation of ODC in vitro in an extract from ODC-overproducing Chinese-hamster ovary cells. PMID- 1590756 TI - Expression in Escherichia coli of a sub-gene encoding the lipoyl and peripheral subunit-binding domains of the dihydrolipoamide acetyltransferase component of the pyruvate dehydrogenase complex of Bacillus stearothermophilus. AB - A sub-gene encoding the N-terminal 170 residues of the dihydrolipoamide acetyltransferase chain of the pyruvate dehydrogenase multienzyme complex of Bacillus stearothermophilus was over-expressed in Escherichia coli. The expressed polypeptide consists of the lipoyl domain, inter-domain linker and peripheral subunit-binding domain; these were found to have folded into their native functional conformations as judged by reductive acetylation of the lipoyl domain, limited proteolysis of the linker region and ability to bind the dihydrolipoamide dehydrogenase dimer. The di-domain was largely (80%) unlipoylated; a small proportion (4%) was correctly modified with lipoic acid and the remainder (16%) was aberrantly modified with octanoic acid. A polyclonal antiserum was raised that recognized both the di-domain and the individual component domains. The 400 MHz 1H-n.m.r. spectrum of the di-domain showed resonances corresponding to those seen in spectra of the lipoyl domain, plus others characteristic of amino acid residues in the flexible linker region. Further, as yet unidentified, resonances are likely to be derived from the peripheral subunit-binding domain. The existence and independent folding of the peripheral subunit-binding domain is thus confirmed and its purification in large-scale amounts for detailed structural analysis is now possible. PMID- 1590757 TI - Mouse serum amyloid A protein. Complete amino acid sequence and mRNA analysis of a new isoform. AB - Four serum amyloid A protein (SAA) genes and two gene products, apo-SAA1 and apo SAA2 were identified in BALB/c mice (type A). SJL/J mice (type B) are thought to be defective in apo-SAA2 expression. A unique variant of mouse apo-SAA was identified in SJL/J mice by isoelectric-focusing analysis of high-density lipoprotein from endotoxin-treated mice. Complete amino-acid-sequence analysis of this quantitatively major form of SJL/J apo-SAA (pI 5.9) showed it to be identical with the apo-SAA2 isoform from BALB/c mice, except for the substitution of aspartic acid for alanine at position 101. Isoform-specific analysis of mRNA from liver of BALB/c and SJL/J mice and their F1 hybrid progeny (CSJLF1/J) mice revealed further differences in the 3' untranslated regions of the genes, not only encoding apo-SAA2 and apo-SAA pI 5.9, but also apo-SAA1. The SAA genes of SJL/J mice thus differ from BALB/c in exon 4. Additional minor isoforms corresponding to apo-SAA2 (pI 6.3) in SJL/J mice and apo-SAA (pI 5.9) in BALB/c mice were identified. We propose that, when analysing a multigene family such as SAA, thorough analysis at the protein level should complement molecular biological approaches where the use of a too-limited repertoire of probes can obscure complexities. PMID- 1590758 TI - Calmodulin binding distinguishes between beta gamma subunits of activated G proteins and transducin. AB - The interactions between guanine nucleotide regulatory proteins and the Ca(2+) binding protein calmodulin were studied using calmodulin-Sepharose affinity chromatography. Purified bovine brain beta gamma subunits bound to calmodulin Sepharose in a Ca(2+)-dependent manner. On the contrary, beta gamma subunits produced in an activated Go/Gi preparation did not bind to calmodulin-Sepharose. The effect was independent of the type of bovine brain G protein (Go/Gi, Gs), method of activation and the presence of magnesium. To distinguish whether the binding of purified beta gamma subunits to calmodulin was unique to brain beta gamma or to the method of purification, similar experiments were performed using transducin. In contrast to bovine brain G proteins, both purified transducin beta gamma subunits and beta gamma released from rhodopsin-activated transducin bound to calmodulin-Sepharose in a Ca(2+)-dependent manner. To assess the functional significance of the binding of bovine brain beta gamma subunits to calmodulin, the ability of purified beta gamma and of beta gamma in unactivated and activated Go/Gi to inhibit partially purified calmodulin-sensitive adenylate cyclase was determined. Purified beta gamma was highly effective in inhibiting calmodulin stimulated adenylate cyclase activity. However, unactivated Go/Gi and preactivated Go/Gi inhibited calmodulin-stimulated adenylate cyclase activity to the same extent. This Go/Gi-mediated inhibition also occurred in the presence of a 500-fold molar excess of calmodulin over added G protein. These results demonstrate: (1) that beta gamma subunits may not be completely released upon G protein activation, and (2) that inhibition of calmodulin-stimulated adenylate cyclase by beta gamma subunits does not appear to be mediated by a direct beta gamma-calmodulin interaction. Differences in the binding properties of activated bovine brain G proteins versus those of transducin could be explained by differences in the gamma subunit between the proteins, or by differences in affinities of the alpha and beta gamma subunits for each other and for calmodulin. The different functional properties of purified beta gamma subunits and beta gamma subunits produced in situ by activation of G proteins indicates that extrapolation from the effects of purified subunits to events occurring in membranes should be done with caution. PMID- 1590759 TI - Biochemical studies on the activity of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D valine synthetase from Streptomyces clavuligerus. AB - The enzyme activity of purified delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (ACV) synthetase from Streptomyces clavuligerus was studied biochemically. The dependence of ACV synthetase activity on reaction parameters, including substrates, cofactors, temperature and pH, were determined, resulting in a substantially increased enzyme activity. The activity is very labile to high temperature and is also unstable at acidic pH. The enzyme specificity is strict towards L-alpha-aminoadipate, but rather loose with respect to L-valine; certain modifications of L-cysteine can also be tolerated. Some unnatural tripeptides synthesized by ACV synthetase can be converted into bioactive compounds by isopenicillin N synthase. The only nutrient found to negatively affect ACV synthetase activity is phosphate, but various compounds such as thiol-blocking reagents and ATP-utilization products (AMP and pyrophosphate) are inhibitory to the enzyme. PMID- 1590760 TI - DNA methylation inhibits transcription of procollagen alpha 2(I) promoters. AB - Our previous studies have demonstrated that a 2-[N-(acetoxyacetyl)amino]fluorene transformed rat epithelial-like cell line, W8, contains a transcriptionally inactive alpha 2(I) gene with a hypermethylated promoter/first-exon region. We have cloned the rat promoter/first-exon region (-211 to +207) from W8 cells and their parent cell line, K16, which expresses alpha 2(I) collagen. There were no sequence differences between the clones from the two cell lines, indicating that a mutation was not responsible for transcriptional inhibition. The alpha 2(I) rat promoters were cloned upstream of the chloramphenicol acetyltransferase gene. Both constructs were equally active in both cell lines, suggesting that trans activating factors for alpha 2(I) transcription are present in W8 cells. Finally, methylation of plasmids at all CpG sites with SssI methylase completely inhibited transcription using alpha 2(I) promoters, but methylation did not inhibit simian virus-40 promoter-driven transcription. Certain methylation sites partially inhibit promoter activity. An HhaI methylation site inhibited transcriptional activity of the alpha 2(I) promoter 8-fold, whereas methylation at the HpaII site in the rat alpha 2(I) promoter did not decrease transcriptional activity. This provides further evidence that methylation at specific sites in the collagen alpha 2(I) promoter is responsible for the inactivation of transcription in W8 cells. PMID- 1590761 TI - Cis- and trans-acting elements required for constitutive and cytokine-regulated expression of the mouse complement C3 gene. AB - The third component of complement (C3) is an important mediator of inflammation. Murine and human genomic cosmid clones were isolated, characterized and sequenced 5' to the complement C3 gene transcriptional initiation sites to determine cis elements that participate in constitutive and regulated C3 gene expression. The murine and human 5' flanking regions are 51% identical overall, with positions 36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but deletion and transfection analysis using reporter gene constructs in HepG2 cells indicated that only the TATA element at position -30, together with sequences -395 to -111, are essential for constitutive expression of murine C3 in hepatocytes. Deletion analysis also suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Sequences between -90 to -41 confer both enhancer activity and interleukin-1/-6 (IL-1/IL-6) responsiveness. Mutation analyses showed that both sequences between -88 and -83 and -77 to -72 are essential for enhancer activity and responsiveness to IL-1, but only sequences between -88 and -83 are necessary for IL-6-responsiveness. A gel-retardation assay showed that several nucleoproteins, perhaps of the C/EBP family, from HepG2 cells bound to sequences between -88 to -83. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6 regulated murine C3 gene expression and provide evidence for specific transacting factors. PMID- 1590762 TI - Factors influencing triacylglycerol synthesis in permeabilized rat hepatocytes. AB - Rat hepatocytes were treated with Staphylococcus aureus alpha-toxin to permeabilize their plasma membrane for low-molecular-mass compounds. During incubation with 1 mM labelled fatty acid, phosphatidate and, less clearly, lysophosphatidate rapidly reached a steady state, whereas labelled diacylglycerol accumulated to some extent, at least in the absence of exogenous CDP-choline. Esterification and oxidation were linearly related to the fatty acid concentration, and there was no indication for saturation with acyl-CoA. However, when permeabilized cells were incubated with labelled sn-glycerol 3-phosphate and 1 mM unlabelled fatty acid, glycerolipid synthesis and the level of esterification intermediates reached a plateau between 0.25 and 0.50 mumol of the triose phosphate/ml. The synthesis of phosphatidylcholine was dependent on addition of CDP-choline. In presence of the latter, diacylglycerol no longer accumulated and triacylglycerol synthesis was suppressed, although the sum of synthesized diacylglycerol, triacylglycerol and phosphatidylcholine remained constant. This indicates that the same pool of diacylglycerol is shared by choline-phosphotransferase and diacylglycerol acyltransferase and that the relative activity of these enzymes depends on the CDP-choline supply. Comparison of the levels of the esterification intermediates with the activity of the respective steps of the pathway reveals that, at a fixed fatty acid concentration, glycerophosphate acyltransferase determines the esterification rate, whereas lysophosphatidate acyltransferase and, at low CDP-choline levels, diacylglycerol acyltransferase approach saturation at elevated sn-glycerol 3 phosphate concentration. There is, however, no indication for a regulatory role of phosphatidate phosphohydrolase in this system. The significance of these findings for the regulation of triacylglycerol synthesis under conditions in vivo is discussed. PMID- 1590763 TI - Overexpression of the wild-type gene coding for Escherichia coli DNA adenine methylase (dam). AB - The gene coding for Escherichia coli dam methylase was isolated from a dam+ K12 strain by the PCR method. The gene was subcloned into an overexpression vector under the control of the strong lambda PL promoter. The resultant construct produced the dam methylase at about 20% of total cellular protein. Purification of the protein was achieved with two chromatography columns and yielded 6 mg of pure methylase per gram cell paste. The methylase readily methylates the synthetic dodecamer GACTGATCAGTC containing its recognition sequence (underlined). It also methylates a synthetic dodecamer containing the EcoRV recognition sequence GATATC. However, methyl transfer is to the second adenine in the EcoRV sequence. PMID- 1590764 TI - DNA methylation pattern changes during development of a sea urchin. AB - Cytosine methylation of developmentally regulated genes of the sea urchin Strongylocentrotus purpuratus was studied by using restriction-endonuclease digestion and Southern blotting. The single-copy bindin gene, the family of five cytoplasmic actin genes and the 400-fold-repeated set of five early histone genes were mostly unmethylated, but some sites exhibited partial methylation that varied throughout development. This shows that in echinoderms the methylation of DNA is not confined to the non-transcribed portion of the genome, as previously believed [Bird, Tagart & Smith (1979) Cell 17, 889-901], and may play a role in transcriptional regulation. PMID- 1590765 TI - Uptake of the antitrypanosomal drug 5'-([(Z)-4-amino-2-butenyl]methylamino)-5' deoxyadenosine (MDL 73811) by the purine transport system of Trypanosoma brucei brucei. AB - An irreversible inhibitor of S-adenosyl-L-methionine decarboxylase (AdoMetDC), 5' ([(Z)-4-amino-2-butenyl]methylamino)-5'-deoxyadenosine (MDL 73811), was found to cure Trypanosoma brucei brucei and multidrug-resistant T. b. rhodesiense infections in mice [Bitonti, Byers, Bush, Casara, Bacchi, Clarkson, McCann & Sjoerdsma (1990) Antimicrob. Agents Chemother. 34, 1485-1490]. Doses of this drug which resulted in a rapid clearance of parasites from T. b. brucei-infected rats resulted in plasma levels of 50-60 microM-MDL 73811 and an intratrypanosomal MDL 73811 concentration of 1.9 mM within 10 min of administration [Byers, Bush, McCann & Bitonti (1991) Biochem. J. 274, 527-533[. Based on this finding we speculated that MDL 73811, which is an adenosine analogue, is a substrate for the trypanosome active purine transport system. We now report evidence that supports this hypothesis. MDL 73811 uptake by T. b. brucei in vitro was time- and temperature-dependent and was saturable over a time course in which MDL 73811 metabolism was undetectable, suggesting that MDL 73811 uptake is a transport mediated phenomenon. Inhibition of MDL 73811 uptake by purine nucleosides is consistent with the drug being a substrate for the trypanosome purine transport system. The accumulation of MDL 73811 by cultured L1210 mouse leukaemia cells was significantly less than by trypanosomes exposed to the same pharmacologically relevant concentrations of MDL 73811. Given that the half-life of MDL 73811 in the plasma of rats and mice is approx. 10 min, it seems likely that the existence of a highly active parasite transport system for MDL 73811 is crucial for the sensitivity of trypanosomes towards MDL 73811 in vivo, and that the absence of active transport of MDL 73811 by the host's cells may play a role in the selectivity of this drug. PMID- 1590766 TI - Increases in intestinal glucose absorption and hepatic glucose uptake elicited by luminal but not vascular glutamine in the jointly perfused small intestine and liver of the rat. AB - 1. Previous studies have shown that an arterial-to-portal glucose concentration gradient may be an important signal for insulin-dependent net hepatic glucose uptake. It is not known whether intestinal factors also contribute to the regulation of hepatic glucose utilization. This problem was studied in a newly developed model which allows luminal perfusion of the small intestine via the pyloric sphincter and a combined vascular perfusion of the small intestine via the gastroduodenal artery and superior mesenteric artery, and of the liver via the hepatic artery and portal vein. 2. In both the presence and the absence of 1 mM-glutamine in the vascular perfusate, only about 7% of a luminal bolus of 5500 mumol (1 g) of glucose was absorbed by the small intestine, and nothing was taken up by the liver. 3. With small doses of 75-380 mumol (11-55 mg) of luminal glutamine, but not with 300 mumol of alanine, the intestinal absorption of the luminal glucose bolus was increased almost linearly from 7% to a maximum of 40% and the hepatic uptake from 0% to a maximum of 22%. 4. The increase of hepatic glucose uptake caused by luminal glutamine was only observed when the glucose load was applied into the intestinal lumen, rather than into the superior mesenteric artery. 5. The relative hepatic glucose uptake (uptake/portal supply) was enhanced from 0% to 55% with an increase in portal supply by luminal glutamine, whereas with a similar range of portal glucose supply the relative hepatic uptake by the isolated liver, perfused simultaneously via the hepatic artery and portal vein, was slightly decreased, from 20% to 15%. 6. Addition of various amounts of portal glutamine and/or alterations in the Na+ content of the portal perfusate failed to mimic the luminal glutamine-dependent activation of hepatic glucose uptake. Therefore the luminal-glutamine-elicited activation of hepatic glucose uptake was apparently not caused by a simple increase in the portal-arterial glucose gradient, by glutamine itself or by Na(+)-dependent alterations in hepatic cell volume. The results suggest that luminal glutamine caused not only an increase in intestinal glucose absorption by unknown mechanisms but also the generation of one or more humoral or nervous 'hepatotropic' signals in the small intestine which enhanced the hepatic uptake of absorbed glucose. PMID- 1590767 TI - Protein kinase C group B members PKC-delta, -epsilon, -zeta and PKC-L(eta). Comparison of properties of recombinant proteins in vitro and in vivo. AB - Of the recently identified protein kinase C (PKC) types of group B (delta, epsilon, zeta, eta, PKC-L), only PKC-epsilon has been characterized in great detail. In order to compare the regulatory and catalytic properties of these new kinases, we have expressed PKC-delta, -epsilon, -zeta and PKC-L as recombinant proteins from their cDNAs in insect cells via baculovirus vectors and in mammalian COS-1 cells. After expression in insect cells, phorbol ester binding and kinase activities of the group B enzymes were compared with the respective activities of a member of group A, PKC-gamma. Although PKC-delta and PKC-L(eta) bind phorbol ester to a similar or the same extent as PKC-gamma, they show a distinctively different behaviour towards conventional PKC substrates such as histone, myelin basic protein, protamine and protamine sulphate, suggesting either that phorbol esters are not able to fully activate these enzymes or that their substrate specificities are very different from those of the group A enzymes. PKC-zeta, a polypeptide of 80 kDa, does not bind phorbol ester and does not phosphorylate these substrates to a significant extent. Consistent with their ability to bind phorbol ester, recombinant PKC-delta and PKC-epsilon are down regulated in COS cells by prolonged treatment with phorbol ester, whereas PKC zeta protein levels remain unaltered. PMID- 1590768 TI - Substrate-specificity of benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase encoded by TOL plasmid pWW0. Metabolic and mechanistic implications. AB - The substrate-specificities of benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase, encoded by TOL plasmid pWW0 of Pseudomonas putida mt-2, were determined. The rates of benzyl alcohol dehydrogenase-catalysed oxidation of substituted benzyl alcohols and reduction of substituted benzaldehydes were independent of the electronic nature of the substituents at positions 3 and 4. Substitutions at position 2 of benzyl alcohol affected the reactivity of benzyl alcohol dehydrogenase: the velocity of the benzyl alcohol dehydrogenase-catalysed oxidation was lower for compounds possessing electron-withdrawing substitutions. In the reverse reaction of benzyl alcohol dehydrogenase, none of the substitutions tested influenced the apparent kcat. values. The rates of benzaldehyde dehydrogenase-catalysed oxidation of substituted benzaldehydes were influenced by the electronic nature of the substitutions: electron-withdrawing groups at positions 3 and 4 favoured the oxidation of benzaldehydes. Substitution at position 2 of benzaldehyde greatly diminished the benzaldehyde dehydrogenase catalysed oxidation. Substitution at position 2 with electron-donating groups essentially abolished reactivity, and only substitutions that were strongly electron-withdrawing, such as nitro and fluoro groups, permitted enzyme-catalysed oxidation. The influence of the electronic nature and the position of substitutions on the aromatic ring of the substrate on the velocity of the catalysed reactions provided some indications concerning the transition state during the oxidation of the substrates, and on the rate-limiting steps of the enzymes. Pseudomonas putida mt-2 containing TOL plasmid pWW0 cannot grow on toluene derivatives substituted at position 2, nor can it grow on 2-substituted benzyl alcohols or aldehydes. One of the reasons for this may be the substrate specificities of the benzyl alcohol dehydrogenase and benzaldehyde dehydrogenase. PMID- 1590769 TI - Characterization of GTP-binding proteins in Golgi-associated membrane vesicles from rat adipocytes. AB - We have previously reported that guanine nucleotides inhibit glucose transport activity reconstituted from adipocyte membrane fractions. In order to further investigate the hypothetical involvement of guanine-nucleotide-binding proteins (GTP-binding proteins) in the regulation of insulin-sensitive glucose transport activity, we studied their subcellular distribution in adipocytes treated or not with insulin. Adipocytes were homogenized and fractionated to yield plasma membranes (PM) and a Golgi-enriched fraction of intracellular membranes (low density microsomes, LDM). In these membrane fractions, total guanosine 5'-[gamma [35S]thio]triphosphate ([35S]GTP[S]) binding, alpha- and beta-subunits of heterotrimeric G-proteins, proto-oncogenes Ha-ras and K-ras, and 23-28 kDa GTP binding proteins were assayed. The levels of alpha s and alpha i (the alpha subunits of Gs and Gi) were approx. 8-fold lower in LDM than in PM; beta subunits, Ha-ras and K-ras were not detectable in LDM. Total GTP[S]-binding sites and 23-28 kDa GTP-binding proteins were present in LDM in approximately the same concentrations as in PM. Insulin gave rise to the characteristic translocation of glucose transporters, but failed to alter the subcellular distribution of any of the GTP-binding proteins. Fractionation of the LDM on a discontinuous sucrose gradient revealed that alpha s and alpha i, as detected with antiserum against a common peptide sequence (alpha common), and the bulk of the 23-28 kDa G-proteins sedimented at different sucrose densities. None of the GTP-binding proteins co sedimented with glucose transporters. Furthermore, the inhibitory effect of GTP[S] on the reconstituted transport activity was lost in the peak fractions of glucose transporters partially purified on the sucrose gradient. These data indicate that LDM from adipocytes contain several GTP-binding proteins in discrete vesicle populations. However, the intracellular GTP-binding proteins are not tightly associated with the vesicles containing the glucose transporter. PMID- 1590770 TI - Isolation of different high-Mr mucin species from human whole saliva. AB - By using CsCl-density-gradient ultracentrifugation, two high-Mr mucin species were isolated from human whole saliva, having buoyant densities in 0.2 M guanidinium chloride of approx. 1.56 g/ml (pool IA) and 1.48 g/ml (pool IIA). Analytical density-gradient centrifugation of submandibular, sublingual, labial and palatal saliva, followed by immunochemical analysis with anti-mucin monoclonal antibodies, indicated immunochemical and physicochemical similarities between the high-density mucins of pool IA and mucins from palatal salivary glands. Chemical analysis indicated that the putative palatal mucin was rich in sulphate, but poor in sialic acid. The lower-density mucins of pool IIA equated with the high-Mr mucins of submandibular-sublingual saliva, both immunochemically and physicochemically (buoyant density). PMID- 1590771 TI - Chitin-binding proteins in potato (Solanum tuberosum L.) tuber. Characterization, immunolocalization and effects of wounding. AB - Tubers of potato (Solanum tuberosum L.) contain a number of chitin-binding proteins which have possible functions in defence against pathogens. A major protein of the tuber is the chitin-binding lectin which has been further characterized with respect to its antigenicity and N-terminal amino acid sequence. By using an antiserum monospecific for tuber lectin in unwounded potato the protein was found in the cytoplasm and vacuole, unusually for a hydroxyproline-rich glycoprotein, but consistent with its soluble nature in subcellular extracts. Little increased synthesis of the lectin precursor or the post-translationally modified form could be demonstrated in excised potato tuber discs. However, after wounding there is increased synthesis of another hydroxyproline-containing glycoprotein of Mr 57,000, which binds to chitin and shares common epitopes with the lectin. In comparison with the tuber lectin, this novel glycoprotein contains less hydroxyproline, but from its overall composition it is clearly not an underhydroxylated form of the tuber lectin. It differed in its N-terminal amino acid sequence and was much less glycosylated, although arabinose was still present. Synthesis of the Mr-57,000 polypeptide began after the initial burst of protein synthesis and increased, reaching a peak at 24 h after wounding. The protein was produced with its enzymes of post-translational modification, prolyl hydroxylase and arabinosyltransferase, concomitantly with the marker enzymes for wounding, phenylalanine ammonia-lyase and membrane-bound phenol oxidase and peroxidase. PMID- 1590772 TI - Purification and characterization of echinoderm casein kinase II. Regulation by protein kinase C. AB - Casein kinase II (CKII) is one of several protein kinases that become activated before germinal-vesicle breakdown in maturing sea-star oocytes. Echinoderm CKII was purified over 11,000-fold with a recovery of approximately 10% by sequential fractionation of the oocyte cytosol on tyrosine-agarose, heparin-agarose, casein agarose and MonoQ. The purified enzyme contained 45, 38 and 28 kDa polypeptides, which corresponded to its alpha, alpha' and beta subunits respectively. The beta subunit was autophosphorylated on one major tryptic peptide on serine residues, whereas the alpha'-subunit incorporated phosphate into at least two tryptic peptides primarily on threonine residues. Western-blotting analysis of sea-star oocyte extracts with two different anti-peptide antibodies that recognized conserved regions of the alpha-subunit indicated that the protein levels of the alpha- and alpha'-subunits of CKII were unchanged during oocyte maturation. The purified CKII was partly inactivated (by 25%) by preincubation with protein serine/threonine phosphatase 2A, but protein-tyrosine phosphatases had no effect. The beta-subunit of CKII was phosphorylated on a serine residue(s) up to 0.54 mol of P/mol of beta-subunit by purified protein kinase C, and this correlated with a 1.5-fold enhancement of its phosphotransferase activity with phosvitin as a substrate. CKII was not a substrate for the maturation-activated myelin basic protein kinase p44mpk from sea-star oocytes, nor for cyclic-AMP-dependent protein kinase. These studies point to possible regulation of CKII by protein phosphorylation. PMID- 1590773 TI - Identification and partial purification of the erythrocyte L-lactate transporter. AB - 1. Intact erythrocytes were incubated with 100 microM-4,4'-di isothiocyanostilbene-2,2'-disulphonate (DIDS), a concentration sufficient to inhibit lactate transport irreversibly by 65%. DIDS-labelled proteins were detected by immunoblotting of erythrocyte membrane proteins with an anti-DIDS antibody. Labelled polypeptides of 35-45 kDa in rat erythrocytes, and of 40-50 kDa in rabbit and guinea pig erythrocytes, were detected by this technique. In human erythrocytes, which have 10-fold less transport activity, no labelled polypeptide in this molecular mass range was detected. 2. Labelling of these 35 50 kDa polypeptides was decreased markedly in the presence of the specific inhibitors of lactate transport alpha-cyano-4-hydroxycinnamate and 4,4' dibenzamidostilbene-2,2'-disulphonate (DBDS), which compete with DIDS for binding to the transporter. However, the weakly bound inhibitor 4,4'-dinitrostilbene-2,2' disulphonate (DNDS) afforded little protection against labelling by DIDS. 3. The lactate transporter from rat erythrocytes was solubilized with decanoyl-N-methyl glucamide (MEGA-10) and partially purified by Mono-Q anion-exchange chromatography, with transport activity eluting at 0.1-0.15 M-NaCl. The 35-45 kDa DIDS-labelled polypeptide from rat erythrocytes was eluted in the same peak of protein as lactate transporter activity during Mono-Q chromatography. 4. These observations provide strong evidence that the lactate transporter is a polypeptide of 35-45 kDa in rat erythrocytes and of 40-50 kDa in rabbit and guinea pig erythrocytes. PMID- 1590774 TI - Molecular cloning of a cDNA coding for mouse liver xanthine dehydrogenase. Regulation of its transcript by interferons in vivo. AB - The cDNA coding for xanthine dehydrogenase (XD) is isolated from mouse liver mRNA by cross-hybridization with a DNA fragment of the Drosophila melanogaster homologue. Two lambda bacteriophage overlapping clones represent the copy of a 4538-nucleotide-residue-long transcript with an open reading frame of 4005 nucleotide residues, coding for a putative polypeptide of 1335 amino acid residues. Comparison of the deduced amino acid sequence of the mouse XD with those of the Drosophila and the rat homologues shows a high conservation of this protein (55% identity between mouse and Drosophila, and 94% identity between mouse and rat). RNA blotting analysis demonstrates that interferon-alpha (IFN alpha) and its inducers, i.e. poly(I).poly(C), bacterial lipopolysaccharide (LPS) and tilorone (2,7-bis-[2-(diethylamino)ethoxy]fluoren-9-one), increase the expression of XD mRNA in liver. Poly(I).poly(C) also induces XD mRNA in several other tissues in vivo. Protein synthesis de novo is not required for the elevation of XD mRNA after IFN-alpha treatment, since cycloheximide does not block the induction. The elevation of XD mRNA concentration is relatively fast and precedes the induction of both XD and xanthine oxidase (XO) enzymic activities. PMID- 1590775 TI - Peptidyldiazomethanes. A novel mechanism of interaction with prolyl endopeptidase. AB - Peptidyldiazomethanes with proline in the P1 position were found to be competitive slow-binding inhibitors of prolyl endopeptidase. Progress-curve experiments monitoring the increase in the degree of inhibition with time indicated that the kinetic mechanism involved an initial complex that isomerized to form a tighter complex. Reversibility of the inhibited complex was demonstrated by monitoring the regain of enzyme activity after removal of free inhibitor and dilution into an assay containing competing substrate. The kinetics of the reversal of inhibition indicated a more complicated inhibitory mechanism involving more than one pathway for reversal of the tight complex. A slow-binding mechanism of inhibition has not been previously observed with peptidyldiazomethanes. Incorporation of [3H]Ac-Ala-Ala-Pro-diazomethane into prolyl endopeptidase was observed after denaturation of the inhibited complex. The peptide labelled with [3H]Ac-Ala-Ala-Pro-diazomethane was isolated and found to contain the active-site serine residue. PMID- 1590776 TI - The source of the oxygen atom in the alpha-hydroxyglycine intermediate of the peptidylglycine alpha-amidating reaction. AB - Peptidylglycine alpha-amidating activity catalyses the oxidation of a C terminally glycine-extended peptide to a desglycine alpha-amidated peptide at the expense of ascorbate and O2 in the presence of Cu2+. The reaction involves oxidative N-dealkylation within the terminal glycine residue, with retention of the glycine N atom and release of the remainder as glyoxylate. Recent studies by us and others have revealed that the reaction consists of two steps via a carbinolamide as an intermediate (peptidyl alpha-hydroxyglycine), and also that two separate enzymes derived from a common precursor protein catalyse these steps, formation of the carbinolamide and its conversion into alpha-amide and glyoxylate. As for the mechanism of carbinolamide formation, two distinct pathways can be considered: direct mono-oxygenation at the glycine alpha-C atom and dehydrogenation leading to an imine followed by hydration. To draw a distinction between them, we carried out the reaction with D-Tyr-Val-Gly as the substrate either in the H2(18)O-enriched medium or under an atmosphere of 18O2, and isolated the alpha-hydroxylglycine intermediate. The fast-atom-bombardment mass-spectral analysis demonstrated that the hydroxy O atom comes from O2, but not from H2O, indicating that the alpha-hydroxylation should be a monooxygenase reaction. PMID- 1590777 TI - Inhibition of the amplification reactions of blood coagulation by site-specific inhibitors of alpha-thrombin. AB - Hirudin and hirulog-1 [D-Phe-Pro-Arg-Pro-[Gly]4-desulphohirudin-(54-65)] abrogate the enzyme activities of alpha-thrombin by binding the enzyme simultaneously at its catalytic centre and fibrin(ogen)-recognition exosite. In contrast, hirugen [hirudin-(54-65)] binds alpha-thrombin solely at the fibrin(ogen)-recognition exosite, and competitively inhibits fibrinopeptide A release. To investigate the extent to which the fibrin(ogen)-recognition exosite is involved when alpha thrombin catalyses the amplification reactions of coagulation, we compared the abilities of hirudin, hirulog-1 and hirugen to inhibit simultaneously Factor X, Factor V and prothrombin activation. Whereas 0.1 microM-hirudin and 0.1 microM hirulog-1 (i.e. less than 10% of the concentration of prothrombin in plasma) inhibited Factor X, Factor V and prothrombin activation, 10 microM was the minimum concentration of hirugen to achieve a similar anticoagulant action. Concentrations of hirudin and hirulog-1 equimolar to and 5 times greater than those of alpha-thrombin respectively abrogated Factor V activation by exogenous alpha-thrombin. In contrast, a 500-fold molar excess of hirugen could not. The inability of hirugen to inhibit the activation of the three clotting factors effectively suggests that the fibrin(ogen)-recognition exosite does not play a mandatory role when thrombin activates Factor V. PMID- 1590778 TI - Multisubunit erythroid complexes binding to the enhancer element of the chicken histone H5 gene. AB - We identified the factor(s) that bind to the chicken erythroid-cell-specific histone H5 enhancer region which is located on the 3' end of the gene. In DNAase I footprinting and u.v. cross-linking experiments with nuclear extracts from adult chicken immature erythrocytes, we determined that the trans-acting factor GATA-1 was the predominating protein interacting with the histone H5 enhancer. GATA-2 and GATA-3 were not detected. In contrast, gel-mobility-shift assays and competition experiments demonstrated that several specific complexes formed with the histone H5 enhancer region. Gel-mobility-shift assays with 23 bp oligonucleotides containing the GATA-binding site (AGATAA) of the histone H5 enhancer or of the beta-globin enhancer showed that the GATA sequence was sufficient for the formation of at least five complexes. Diagonal mobility-shift assays demonstrated that multisubunit complexes were forming with the GATA-1 protein. Our interpretation of the results is that GATA-1 interacts with a protein of approx. 105 kDa which, in turn, can associate with protein or protein complexes of approx. 26 kDa, 146 kDa and a protein(s) of molecular mass greater than 450 kDa. The different multisubunit complexes formed via the trans-acting factor GATA-1 may impart different transcriptional responses to the promoter and enhancer elements of the histone H5 and globin genes. PMID- 1590780 TI - Structural distinction of rat GSH transferase subunit 10. PMID- 1590779 TI - Epithelial sphingolipid sorting allows for extensive variation of the fatty acyl chain and the sphingosine backbone. AB - In kidney MDCK and intestinal Caco-2 epithelial cells, glucosylceramide (GlcCer) and sphingomyelin (SPH) synthesized from the short-chain sphingolipid analogue N 6-[7-nitro-2,1,3-benzoxadiazol-4-yl]aminodecanoyl (C6-NBD)-ceramide are delivered to the cell surface with apical/basolateral polarities of 2-4 and 0.6-0.9 respectively. We have tested how variations in the lipid backbone affect these polarities. First, the C6-NBD moiety was replaced by a bare [14C]octanoyl chain or by the even more bulky fluorophores 8-bimanoylthio-octanoyl (C8-bimane) and 8 diethylaminocoumarin-octanoyl (C8-DECA). In addition, the sphingosine in C6-NBD ceramide was changed in stereoconfiguration (L-threo) or saturation (dihydro). In all cases, GlcCer and SPH were produced and appeared on the cell surface at 37 degrees C, as assayed by back-exchange. The apical/basolateral polarity of the delivery of GlcCer was variable, but always exceeded 1. GlcCer was apically enriched over SPH (2-6 times for MDCK and 3-9 times for Caco-2). Even GlcCer synthesized from a highly water-soluble truncated ceramide (octanoyl-D-erythro sphingosine analogue with C8 backbone) was enriched apically by a factor of greater than or equal to 2 both in absolute polarity and compared with SPH. Sphingolipid sorting was quantitatively but not qualitatively affected by dramatic changes in the lipid backbone. PMID- 1590781 TI - Formation of nitrogen oxides and citrulline upon oxidation of N omega-hydroxy-L arginine by hemeproteins. AB - HRP catalyzes the oxidation of N omega-hydroxy-L-arginine (NOHA) by H2O2 with formation of citrulline and NO2- with initial rates of about 0.7 and 0.2 nmol per nmol HRP per min. In the same manner, cytochromes P450 from rat liver microsomes catalyze the oxidation of NOHA to citrulline and NO2- by cumylhydroperoxide. Inhibitors of these hemeproteins (N3- and CN- for HRP and miconazole for P450) strongly inhibit both citrulline and NO2- formation. Rates of NOHA oxidation by these hemeproteins markedly decrease with time presumably because of their denaturation by nitrogen oxides and of the formation of hemeprotein-iron-NO complexes. These results suggest that NO (and other nitrogen oxides) could be formed from oxidation of NOHA by other enzymes than NO-synthases. PMID- 1590782 TI - The genetic organization of the mau gene cluster of the facultative autotroph Paracoccus denitrificans. AB - The mau gene cluster from Paracoccus denitrificans was cloned. The regions of a cloned fragment carrying genes for the small and the large subunit of the methylamine dehydrogenase were identified and sequenced. Open reading frames for the MADH small subunit gene and the MADH large subunit gene were identified. Three other open reading frames coding polypeptides with unknown function were found in the sequence. The small subunit gene sequence data reveal that the MADH small subunit polypeptide from P. denitrificans has an unusual leader sequence and contains the tryptophan tryptophyl quinone cofactor. The MADH small subunit genes and the parts of the open reading frames found upstream of them in the genome of M. extorquens AM1 and P. denitrificans have considerable similarity. The sequence data have been used for refinement of the X-ray crystallographic structure of the MADH from P. denitrificans, and key conserved residues have been identified. PMID- 1590783 TI - Melanins production from enkephalins by tyrosinase. AB - Leu-enkephalin and Met-enkephalin are oxidized in vitro by mushroom and sepia tyrosinase giving rise to synthetic melanins whose production is dependent on incubation time and on enzyme concentration. The Enk-melanins formed are acid insoluble brownish or reddish pigments showing a continuous absorbance in the visible region when dissolved in basic solution. The presence of the amino acid chain makes them fully soluble in pH 7.4 0.05 M phosphate buffer and methanol. PMID- 1590784 TI - A novel regulatory protein that affects the functions of caldesmon and myosin light chain kinase. AB - A caldesmon (CaD)-binding protein of about 65 kDa (by SDS-PAGE) was purified from smooth muscle of chicken gizzard. The 65-kDa protein prevented the inhibitory effect of CaD on the ATP-dependent interaction between actin and myosin. Unlike the case with calmodulin (CaM), Ca2+ was not required for this effect. As reported in the preceding communication, myosin light chain kinase (MLCK), another well characterized protein that binds CaM, has CaD-like activity that modulates the interaction by binding to actin. The 65-kDa protein was also effective in relieving the modulation, while leaving unaffected the kinase activity that phosphorylates the light chain of smooth muscle myosin. PMID- 1590785 TI - A transcription-dependent DNase I-hypersensitive site in a far upstream segment of the chicken alpha-globin gene domain coincides with a matrix attachment region. AB - A site of hypersensitivity to DNase I has been found at the 5'-side of the chicken alpha-globin gene domain, ca. 8 Kbp upstream to the first gene. The presence of this site in different types of chicken cells correlates with the transcriptional status of the domain. A matrix attachment region (MAR) has also been found in the same subfragment, suggesting that it may be involved in the control of transcription of the chicken alpha-globin genes. PMID- 1590786 TI - Differential expression of a novel murine non-receptor protein tyrosine phosphatase during differentiation of P19 embryonal carcinoma cells. AB - Protein phosphorylation on tyrosine residues is one of the major mechanisms of cell signal transduction and is regulated by protein tyrosine kinases and protein tyrosine phosphatases. Here we report the molecular cloning of an additional member of the protein tyrosine phosphatase-family from differentiated murine P19 embryonal carcinoma cells. This non-receptor protein tyrosine phosphatase, P19 PTP, does not contain regulatory sequences, homologous to the ones found in other non-receptor PTPases. P19-PTP is differentially expressed during in vitro differentiation of P19 EC cells, in that P19-PTP mRNA could only be detected in embryoid bodies, derived from P19 cells. PMID- 1590787 TI - Purification and properties of an iminopeptidase from culture media of Streptomyces plicatus. AB - The degradation of the prosequence of the secreted enzyme endo-beta-N acetylglucosaminidase H from Streptomyces plicatus is not elucidated. Both the primary structure of this segment and the finding that the secreted species contain ragged aminoterminal ends of specific structure suggested that a dipeptidylaminopeptidase might mature this enzyme. Therefore, we tested the culture medium of Streptomyces plicatus for prolin-specific peptidases. Proline iminopeptidase was purified about 800-fold to homogeneity from the culture medium. Dipeptidylaminopeptidase, the enzyme that seemed most likely to process the prosequence of endo-beta-N-acetylglucosaminidase H, could not be detected. PMID- 1590788 TI - The primary structure of mouse saposin. AB - The primary structure of mouse sphingolipid activator protein (saposin) was determined by cDNA sequencing. The amino acid sequence predicted by the cDNA sequence revealed that mouse saposin was highly homologous to human saposin and also to rat sertoli cell glycoprotein. Mouse saposin also has four functional domains, which are structurally similar to each other, and each domain has cysteines, prolines, and a potential glycosylation site at an almost identical position. An amino acid comparison between human and mouse saposins revealed that the similarity was approximately 70%, and human saposin lacks thirty-one amino acids between domains C and D. Heterogeneities of mRNA were found in both the coding and noncoding regions. PMID- 1590789 TI - Serine analogues of hFSH-beta-(33-53) and hFSH-beta-(81-95) inhibit hFSH binding to receptor. AB - Synthetic peptides corresponding to hFSH-beta-(33-53) and hFSH-beta-(81-95) each contain free sulfhydryl groups, inhibit binding of FSH to receptor and are partial agonists of estradiol synthesis in Sertoli cells. Recently, we have reported that sulfhydryl groups are important in FSH- receptor interaction and that peptides containing free sulfhydryl groups or disulfide bridges, such as glutathione, may nonspecifically inhibit FSH binding to receptor. In the present study, Cys residues of hFSH-beta-(33-53) and hFSH-beta-(81-95) were replaced by Ser residues and the peptides tested for their ability to inhibit binding of FSH to receptor. Results similar to those obtained previously with natural sequence peptides were obtained with the Ser analogs, indicating that Cys residues were not essential for binding inhibition. However, the partial agonist activity of the hFSH-beta-(33-53) and (81-95) in cultured Sertoli cells could not be detected when Cys residues were replaced by Ser. Thus, replacement of Cys residues with Ser does not effect receptor binding activity but is deleterious to the agonist activity of these peptides. PMID- 1590790 TI - Feedback-type inhibition of activity of 3-hydroxy-3-methylglutaryl coenzyme a reductase by ubiquinone. AB - Accompanying the decrease in serum cholesterol and increase in concentration of ubiquinone in liver and its microsomes, the activity, but not the protein, of HMG CoA reductase decreased in ubiquinone-supplemented rats. A soluble 58-kDa preparation of HMG-CoA reductase was partially inhibited on addition of ubiquinone indicating a possible feedback type of action. PMID- 1590791 TI - The third molecule associated with interleukin 2 receptor alpha and beta chain. AB - It is known that the affinity cross-linking study of the human high-affinity Interleukin 2 (IL-2) receptor reveals triplet bands consisting of 70 kDa alpha chain(Tac)-IL-2 and the 90/80 kDa doublet. We found the cell lines lacking the lower band of the doublet in spite of the expression of both alpha and beta chains. No IL-2 binding was detectable in the presence of anti-Tac antibody in these cells. Immunoprecipitation from the cell extract of [125 I] IL-2-cross linked T cells with anti-beta chain polyclonal IgG detected the upper band, but not lower band of the doublet. These data suggest that the lower band of the doublet represents an unknown IL-2-binding protein (p65) distinct from the beta chain and this molecule may be involved in the intermediate-affinity IL-2 binding together with the beta chain. PMID- 1590792 TI - Characterization of proteoglycans in Alzheimer's disease fibroblasts. AB - Skin fibroblasts lines established from patients with Alzheimer's disease and old normal individuals were cultured with 35S-sodium sulfate and 3H-glucosamine. Proteoglycans were isolated and characterized. Sulfate incorporation into proteoglycans increased in Alzheimer's disease fibroblasts relative to normal controls. These increases changed the ratio of chondroitin sulfate to heparan sulfate proteoglycan from 1.4 to 1.7 (p = 0.0012) and decreased the ratio of cell to medium proteoglycans from 0.32 to 0.26 in normal and Alzheimer fibroblasts (p = 0.006), respectively. HPLC analysis of the disaccharides produced by chondroitinase ABC revealed no differences in composition between proteoglycans of Alzheimer and normal fibroblasts in either the cell or medium fraction. However, analysis of disaccharides produced by heparinase plus heparitinase showed differences in composition in the medium but not the cell fraction. delta UA-GlcNS was increased by 30% while delta UA-GlcNS-6S was reduced by 40% in Alzheimer's disease. PMID- 1590793 TI - Platelet-derived endothelial cell growth factor has thymidine phosphorylase activity. AB - Platelet-derived endothelial cell growth factor (PD-ECGF), a protein which stimulates angiogenesis in vivo, is shown to have a 39.2% amino acid sequence similarity over a 439 amino acid region with the thymidine phosphorylase of Escherichia coli (E. coli). Using recombinant human PD-ECGF, we show that PD-ECGF has thymidine phosphorylase activity. Analysis by gel chromatography revealed that recombinant human PD-ECGF occurs as a 90 kDa homodimer, similar to other thymidine phosphorylases. In addition to a possible effect on DNA synthesis, PD ECGF was shown to affect [3H]thymidine assays in a manner which is not related to cell proliferation. The in vitro and in vivo effects of PD-ECGF may thus occur by an indirect mechanism through its enzymatic activity. PMID- 1590794 TI - Role of protein kinase C (PKC) in bone resorption: effect of the specific PKC inhibitor 1-alkyl-2-methylglycerol. AB - The specific inhibitor of protein kinase C, 1-O-alkyl-2-O-methylglycerol (AMG), was studied for its effect on bone resorption, measured as 45Ca-release, in fetal mouse calvariae. AMG (1 to 50 microM) had no effect on basal bone resorption. AMG inhibited parathyroid hormone (40 nM) induced bone resorption in a dose-dependent manner. Resorption induced by 1,25 (OH)2-vitamin D3 (10 nM) or prostaglandin E2 (5 microM) was also inhibited by AMG. The release of beta-glucuronidase activity paralleled the course of the 45Ca-release. The production of interleukin 6, induced by parathyroid hormone, in fetal rat calvarial osteoblasts was not affected by AMG. AMG (1 to 50 microM) had no cytotoxic effects on cells or calvariae. From these results it is concluded that protein kinase C may have an important role in the regulation of bone resorption. PMID- 1590795 TI - delta-Aminolevulinate uptake by Rhizobium bacteroids and its limitation by the peribacteroid membrane in Legume nodules. AB - Heme is overproduced during Rhizobium-Legume symbiosis and delta-aminolevulinate (ALA) is a common precursor in both bacterial and plant synthesis pathways of this molecule. ALA uptake by bacteroids from French bean and soybean nodules was characterized. The action of several metabolic inhibitors and the competition effect of malate on this uptake were studied. ALA transport appeared to be mediated by the dicarboxylate carrier system. Purified symbiosomes--bacteroids surrounded by the peribacteroid membrane--failed to accumulate significant amount of ALA. These experiments rule out the possibility for the plant cytosol to provide the bacteroid with ALA and strengthen the restrictive role of the peribacteroid membrane for exchanges between the two symbiotic partners. PMID- 1590796 TI - Exposure to the chlorofluorocarbon substitute 2,2-dichloro-1,1,1- trifluoroethane and the anesthetic agent halothane is associated with transient protein adduct formation in the heart. AB - Hydrochlorofluorocarbons (HCFCs) that are structural analogues of the anesthetic agent halothane may follow a common pathway of bioactivation and formation of adducts to cellular targets of distinct tissues. Exposure of rats to a single dose of HCFC 123 (2,2-dichloro- 1,1,1-trifluoroethane) or its structural analogue halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) in vivo resulted in the formation of one prominent trifluoroacetylated protein adduct (TFA-protein adduct) in the heart. In contrast, a variety of distinct TFA-protein adducts were formed in the liver and the kidney of the same animals. The TFA-protein adduct in the heart was processed rapidly; t1/2 of the intact TFA-protein adduct was less than 12 h. PMID- 1590797 TI - Activin synergistically increased c-jun mRNA in P19 embryonal carcinoma cells in the presence of retinoic acid. AB - Activin and retinoids, which are involved in the induction and regulation of the early differentiation process in vertebrate embryogenesis, synergistically increased the amount of c-jun mRNA in P19 embryonal carcinoma cells, but activin alone had no effect. Among the retinoids, all-trans-retinoic acid most effectively increased c-jun mRNA. Activin (lng/ml) was sufficient to induce the synergistic increase of c-jun mRNA in P19 EC cells with all-trans-retinoic acid. The synergistic increase of the amount of c-jun mRNA by their cooperative action may be important in vertebrate development. PMID- 1590798 TI - Acetylcholine induces vasoconstriction in the microcirculation of cardiomyopathic hamsters: reversal by L-arginine. AB - The goal of this study was to determine whether endothelium-dependent responses of the microcirculation are altered during cardiomyopathy. We examined in vivo responses of cheek pouch arterioles to an endothelium-dependent agonist (acetylcholine) and an endothelium-independent agonist (nitroglycerin) in normal and in cardiomyopathic hamsters. In normal hamsters, acetylcholine produced dose related dilatation of arterioles. In contrast, acetylcholine produced constriction of arterioles in cardiomyopathic hamsters. Nitroglycerin produced similar dose-related dilatation in normal and cardiomyopathic hamsters. We also examined whether impaired responses to acetylcholine in cardiomyopathic hamsters were related to an alteration in the L-arginine/nitric oxide pathway. We found that L-arginine (100 microM) restored endothelium-dependent vasodilatation to acetylcholine in cardiomyopathic hamsters. Thus, cardiomyopathy impairs endothelium-dependent responses of the microcirculation which is reversed by L arginine. PMID- 1590799 TI - Specific activation of a tyrosine----glycine mutant of delta 5-3-ketosteroid isomerase by phenols. AB - A key unknown still to be explored concerning the mechanism of delta 5-3 ketosteroid isomerase from Pseudomonas testosteroni is the extent of the proton transfer between tyrosine-14 of the enzyme and the C-3 carbonyl oxygen of the steroid substrate. This report is a preliminary study of a system we are developing to allow us eventually to use a Bronsted analysis to measure this transfer. We describe the construction of an expression vector and tyrosine-14--- glycine-14 mutant of the enzyme and its specific activation, in the manner of chemical rescue, by a variety of phenolic compounds. We suggest that the binding region of phenol is very tight and that the level of activation may be a result of steric constraints as well as of differences in the pKa' of the phenol. PMID- 1590800 TI - The expression of soluble and cell-bound alpha 2,6 sialyltransferase in human colonic carcinoma CaCo-2 cells correlates with the degree of enterocytic differentiation. AB - alpha 2,6 sialyltransferase towards the N-acetyllactosaminyl sequence (alpha 2,6 ST, E.C. 2.4.99.1) is one of the major sialyltransferases in human colonic cells; it strongly increases in human colorectal tumors and is largely expressed in fetal and neonatal rat colon. In this study we demonstrate that human colon carcinoma CaCo-2 cells, which differentiate spontaneously into enterocytes when maintained confluent for several days, exhibit a very high expression of alpha 2,6 ST both in the cell-bound and soluble form. When the CaCo-2 cells were cultured on porous membranes the soluble alpha 2,6 ST was mainly detected in the medium collected from the chamber corresponding to the basolateral face of the monolayer. The soluble alpha 2,6 ST could be concentrated and purified from the alpha 2,3 sialyltransferase by affinity chromatography on Blue Sepharose. PMID- 1590801 TI - Helicobacter pylori lipopolysaccharide effect on the synthesis and secretion of gastric sulfomucin. AB - The effect of H. pylori lipopolysaccharide on the synthesis and secretion of sulfated mucin in gastric mucosa was investigated using mucosal segments incubated in the presence of [3H]proline, [3H]glucosamine and [35S]Na2SO4. The lipopolysaccharide, while showing no discernible effect on the apomucin synthesis was found to inhibit the process of mucin glycosylation and sulfation, which at 100 micrograms/ml lipopolysaccharide reached the optimal inhibition of 65%. The analysis of mucin secretory responses revealed that the lipopolysaccharide by first 15 min caused a 57% stimulation in sulfomucin secretion followed thereafter by inhibition, which reached maximum of 32% by 45 min. The results suggest that colonization of gastric mucosa by H. pylori may be detrimental to the process of gastric sulfomucin synthesis and secretion. PMID- 1590802 TI - Antagonistic effect of triphenylethylenic antiestrogens on the association of estrogen receptor to calmodulin. AB - Binding of (3H)-estradiol labeled estrogen receptor from uterine cytosol to calmodulin was demonstrated by both affinity chromatography and sucrose gradient sedimentation. Triphenylethylene antiestrogens (tamoxifen family) with strong antagonistic activity against the calmodulin-dependent c-AMP phosphodiesterase largely reduced the binding of the receptor. Relevance of this observation with regard to the major antiproliferative activity (cytotoxicity) of these drugs is discussed. PMID- 1590803 TI - Amyloid beta-protein fragment 25-35 causes activation of cytoplasmic calcium in neurons. AB - The cellular mechanism by which beta-amyloid has its effect on neurons is unknown. Based on observations that endogenous neurotoxins, such as glutamate and platelet activating factor (PAF), cause activation of cytoplasmic calcium, we tested if this was true with beta-amyloid. Using nerve growth factor-treated PC12 cells, we noted that the active beta-amyloid fragment, containing residues 25 to 35, caused a specific and dose-dependent increase in intracellular calcium due to an influx of extracellular calcium. PMID- 1590805 TI - Cloning and modulation by endothelin-1 of rat cardiac K channel. AB - We have cloned a delayed rectifier type K channel from rat heart (RH1). RH1 was identical to the rat brain K channel BK2 and differed from recently cloned rat cardiac K channel RAK by one amino acid residue. Endothelin receptors(ETRs) mediated modulation of RH1 current (IRH1) was studied using Xenopus oocyte expression system. Activation of two different subtypes of ETRs by endothelin-1 equally suppressed the amplitude of IRH1. Stimulation of phosphatidylinositol turnover will probably be responsible for the suppression. PMID- 1590804 TI - Leukocyte adhesion deficiency: identification of novel mutations in two Japanese patients with a severe form. AB - Leukocyte adhesion deficiency is a disorder with mutations of the gene for the beta subunit, a component common to three adhesion molecules; LFA-1, Mac-1 and p150,95. The molecular basis of the disorder was studied in two patients with its severe form. In the first patient, the mutant gene expressed an aberrant mRNA, 1.2 kb longer than usual, resulting from a G to A substitution at the splice donor site of a 1.2 kb intron. Several aberrantly spliced messages, arising from splicing at cryptic donor sites, were also identified. The beta subunit proteins deduced from the mRNA sequences lacked half the carboxyl terminal portion. In the second patient, the mutation was a G to A transition at nucleotide 454, which resulted in an Asp128 to Asn substitution of the beta subunit. The 128th Asp residue is located in a region crucial for the association with alpha subunits and strictly conserved among the integrin beta subunits so far analyzed. PMID- 1590806 TI - Two distinct sequences control the targeting and anchoring of the mouse P450 1A1 into the yeast endoplasmic reticulum membrane. AB - We previously expressed mouse P450 1A1 in the yeast S. cerevisiae. In the present study, I describe experiments in which several deletions in the 5' end of the corresponding cDNA were created. The truncated forms were then expressed in yeast cells. Studies of microsomes obtained from transformed yeast show that the signal sequence is not required in vivo for the integration of mouse P450 1A1 into the endoplasmic reticulum membrane. In addition, the cytochrome deleted for its hydrophobic signal-sequence appears to be enzymatically functional. These results strongly argue for the existence of a second determinant of membrane targeting and binding. PMID- 1590807 TI - Similar-sized daughter-strand gaps are produced in the leading and lagging strands of DNA in UV-irradiated E. coli uvrA cells. AB - The nascent DNA synthesized after UV irradiation contained discontinuity, i.e., daughter-strand gaps. The sizes of these gaps produced in the leading and lagging strands of UV-irradiated Escherichia coli cells were determined by using strand specific DNA probes. The DNA isolated from irradiated uvrA delta(lac-pro) cells was hybridized with the 32P-labeled single-stranded DNA probes. After digestion with S1 nuclease, the sizes of the bound radioactive DNA fragments were determined by electrophoresis in an alkaline agarose gel. It was found that the average size of gaps produced in the leading strand was about 0.12 kb, whereas those produced in the lagging strand was slightly smaller than 0.12 kb. No gaps larger than 0.5 kb were detected. PMID- 1590808 TI - A chimeric actin carrying N-terminal portion of Tetrahymena actin does not bind to DNase I. AB - A chimeric actin gene was constructed from Tetrahymena actin sequence corresponding to residues 1-83 and Dictyostelium actin sequence corresponding to residues 84-375, and the gene was expressed in Dictyostelium cells. Using DNase I affinity column, we revealed that the product of the chimeric actin gene was not retained in the column whereas intrinsic actin was retained. In conjunction with our previous data that Tetrahymena actin does not interact with DNase I [Hirono, M., Kumagai, Y., Numata, O., & Watanabe Y. (1989) Proc. Natl. Acad. Sci. U.S. 86, 75-79], we suggest that the binding site of DNase I in an ubiquitous actin is located in N-terminal region (residues 1-83). PMID- 1590809 TI - Calmodulin regulates DNA polymerase alpha activity during proliferative activation of NRK cells. AB - When Normal Rat Kidney cells are allowed to reenter the cell cycle after quiescence they start to replicate DNA around 12 h, reaching a maximum at 20 h. Activation of DNA polymerase alpha parallels the increase in DNA synthesis. The addition of two different anti-calmodulin drugs, trifluoroperazine (7.5 microM) or W13 (10 micrograms/ml), to the media at 4 h after proliferative activation, inhibits DNA synthesis by 55% and 80%, respectively. The blockade of calmodulin produced by trifluoroperazine allows the cells to progress through G1 phase but stops progression through S phase as determined by 5-Bromo deoxyuridine labeling. Both anti-calmodulin drugs also inhibit by more than 50% the increase in DNA polymerase alpha activity observed at 20 h. These results indicate that a calmodulin-dependent event, essential for the activation of DNA polymerase alpha and subsequently for DNA replication, is produced during G1. Therefore, the control of DNA polymerase alpha activation is one of the ways by which calmodulin is regulating the progression of NRK cells through S phase. PMID- 1590810 TI - Foot currents and ankle SARs induced by dielectric heaters. AB - Data are presented on ankle-specific SARs and foot currents as a function of strengths of radio-frequency electromagnetic fields encountered by operators of dielectric heaters. The determination of foot currents was based on near-field exposures in which reactive coupling dominates, and which can result in substantial SARs in exposed workers. The operators were located less than one wavelength from--usually within one meter of--the dielectric heaters, which generated fields at frequencies from 6.5 to 65 MHz. At distances normally assumed by workers, maximal strengths of electric fields ranged from 10(4) to 2.4 x 10(6) V2/m2; maximal strengths of magnetic fields ranged from 5.0 x 10(-3) to 33.3 A2/m2. Currents through both feet to ground were measured while operators stood where they normally worked. Maximal currents ranged from 3 to 617 mA, rms. Nearly 27 percent of the dielectric heaters induced foot currents that exceeded the 200 mA limit that has been proposed for a new ANSI C95.1 standard. Twenty percent of the heaters induced foot currents that exceeded 350 mA. SARs in ankles were calculated from foot currents, and they approximated 5 W/kg at 100 mA, 29 W/kg at 250 mA, and 57 W/kg at 350 mA. The maximal SAR in the ankle was approximately 176 W/kg at 617 mA. PMID- 1590811 TI - Transcription in Drosophila melanogaster salivary gland cells is altered following exposure to low-frequency electromagnetic fields: analysis of chromosome 3R. AB - The use of the transcription autoradiographic method permits identification of nascent RNA chains directly on identifiable regions of Drosophila salivary gland chromosomes. Changes in transcriptional activity at 13 defined regions of the right arm of chromosome 3 (3R) were observed following 20-min exposures of salivary glands to five different extremely low frequency (ELF) electromagnetic (EM) fields. Changes in translational patterns were also induced by the ELF EM fields in exposed cells. Differences included an increase in over-all polypeptide synthesis as well as in the number of polypeptides resolved in cells exposed to EM fields. PMID- 1590812 TI - Bursting responses of Lymnea neurons to microwave radiation. AB - Microelectrode and voltage-clamp techniques were modified to record spontaneous electrical activity and ionic currents of Lymnea stagnalis neurons during exposure to a 900-MHz field in a waveguide-based apparatus. The field was pulse modulated at repetition rates ranging from 0.5 to 110 pps, or it was applied as a continuous wave (CW). When subjected to pulsed waves (PW), rapid, burst-like changes in the firing rate of neurons occurred at SARs of a few W/kg. If the burst-like irregularity was present in the firing rate under control conditions, irradiation enhanced its probability of occurrence. The effect was dependent on modulation, but not on modulation frequency, and it had a threshold SAR near 0.5 W/kg. CW radiation had no effect on the firing rate pattern at the same SAR. Mediator-induced, current activation of acetyl-choline, dopamine, serotonin, or gamma-aminobutyric-acid receptors of the neuronal soma was not altered during CW or PW exposures and, hence, could not have been responsible for the bursting effect. PMID- 1590813 TI - Calcium binding to metallochromic dyes and calmodulin in the presence of combined, AC-DC magnetic fields. AB - The possibility that weak, ac and dc magnetic fields in combination may affect binding equilibria of calcium-ions (Ca2+) was investigated with two metallochromic dyes as calcium-binding molecules: murexide and arsenazo III. Calcium-dye equilibria were followed by measuring solution absorbances with a fiber-optic spectrophotometer. A Ca(2+)-arsenazo solution was also used indirectly to monitor the binding of Ca2+ to calmodulin. Parallel, ac and dc magnetic fields were applied to each preparation. The ac magnetic field was held constant during each of a series of experiments at a frequency in the range between 50 and 120 Hz (sine wave) or at 50 pps (square wave) and at an rms flux density in the range between 65 and 156 microT. The dc magnetic field was then varied from 0 to 299 microT at 1.3 microT increments. The magnetic fields did not measurably affect equilibria in the binding of metallochromic dyes or calmodulin to Ca2+. PMID- 1590814 TI - An analysis of associations between social class and ambient magnetic fields in metropolitan Melbourne. AB - In the course of a study on residential magnetic-field exposure, some incidental data were obtained that bear on the issue of confounding of magnetic field exposure by social class. We have explored the possibility that the magnetic flux density of 50 Hz fields measured in Melbourne streets is correlated with a number of variables that index the socio-economic status of the neighborhood. We have examined also for a correlation between field-intensity levels and sums of some or all of the indicators, which were weighted to provide an overall score on socio-economic status. Although some of the indexes were weakly, but significantly, correlated with environmental levels of magnetic fields, the combined indices were not. These results indicate that socio-economic status is not likely to be a confounder in epidemiological studies of residential exposure to ELF magnetic fields in Melbourne. PMID- 1590815 TI - High-intensity electrostatic-field exposure system for cultured biological cells. AB - We describe a new system for exposing cultured biological cells that have been plated on coverslips to strong electrostatic fields at magnitudes greater than 10(3) V/cm. Techniques are described that make use of mineral oil to render insignificant electrical conduction currents (total leakage current is less than 1.0 nA or less than 0.1 nA/coverslip), joule heating (less than 10(-6) W), or current-induced magnetic fields (less than 10(-13) T) in regions inhabited by cells. The mineral oil also eliminates a reduction in the strength of the applied field, which otherwise can occur from increased electrode-to-medium impedance at the site of application. Thus the applied field is reliably specified in the vicinity of a cell membrane. Control and electrostatic field chambers are housed in a grounded metal incubator. Cylindrical mu-metal shields can be used to reduce background magnetic fields in each chamber from 40 microT static and approximately 1 microT ac to, respectively, less than 3 microT static and approximately 100 nT ac. Contamination of cells by impurity atoms that may leach from electrodes was measured by atomic-absorption spectrophotometry and found to be negligible. Stray magnetic- and electric-field components within the incubator were measured, as were background fields around the laboratory. PMID- 1590816 TI - Measurements of potential differences in human subjects induced by motion in a superconducting magnetic field. AB - We have attempted to measure the electromotive forces (emfs) induced in human beings moving at a constant speed in a highly dense magnetic field. Experiments were initially conducted on a set of models, and then directly on human subjects. The models consisted of single circular loops of Tygon tubing (I.D., 0.635 cm; O.D., 0.9525 cm) filled with normal saline solution, with circumferences of 20, 40, 60, 80, and 100 cm. The models were connected to an amplifier via silver/silver-chloride electrodes. Each saline loop was mounted on a movable platform, with the plane of the loop perpendicular to the platform's axis; the platform was enabled to move at known constant speeds into and out of the bore of a 1.89-T magnet. The human subjects were then substituted for the saline loops, with the long axis parallel to the direction of motion, and with standard EKG electrodes placed at 180 degrees successively on the ankle, calf, lower thigh, upper thigh, chest, and head. In all cases, for human subjects and models, the peak induced voltage was directly proportional to the speed of movement and the square of the circumference of the bounded cross-sectional areas. Thus, for the saline loops, the correlation coefficient between induced voltage and circumference was .998, and for human subjects, .947. Under the loose assumption that for equal circumferences the bounded areas in human subjects were equal to those in the circular loops, the induced emfs in human subjects were consistently about 13% greater than those in the loops. At a mean speed of 1.18 m/s, the chest had a peak induced voltage of 260 mV, while the voltage at the ankle had a peak of 19.8 mV. The experimental data were used to estimate the corresponding induced current density at the pericardium, 17 mA/m2. We conclude for a human subject moving at constant speed along the body's long axis into a magnetic field that Faraday's law is closely followed for various cross-sections of the body. Further, in those cases in which the magnetic field and its gradient are not well established, one can use saline-filled loops to estimate approximate values of voltages induced in human subjects. PMID- 1590817 TI - ELF exposure facility for human testing. AB - A laboratory facility specifically designed for controlled human exposure to 60 Hz electric (0 to 16 kV/m) and magnetic (0 to 32 A/m, B = 0 to 40 microT) fields has been constructed. The facility presents uniform fields under controlled temperature and humidity. Special control systems allow collection of physiological data during, as well as before and after, exposure to electric fields at strengths to 16 kV/m under verified double-blind control. Exposure to continuous or intermittent fields is possible in the facility. The capability of obtaining physiological data during actual exposure to constant or intermittent, 60-Hz fields, and of doing so without either the subject or the experimenter being aware of actual field conditions, is a critical factor in valid experimentation. PMID- 1590818 TI - ELF in vitro exposure systems for inducing uniform electric and magnetic fields in cell culture media. AB - Many in vitro experiments on the biological effects of extremely low frequency (ELF) electromagnetic fields utilize a uniform external magnetic flux density (B) to expose biological materials. A significant number of researchers do not measure or estimate the resulting electric field strength (E) or current density (J) in the sample medium. The magnitude and spatial distribution of the induced E field are highly dependent on the sample geometry and its relative orientation with respect to the magnetic field. We have studied the E fields induced in several of the most frequently used laboratory culture dishes and flasks under various exposure conditions. Measurements and calculations of the E field distributions in the aqueous sample volume in the containers were performed, and a set of simple, quantitative tables was developed. These tables allow a biological researcher to determine, in a straightforward fashion, the magnitudes and distributions of the electric fields that are induced in the aqueous sample when it is subjected to a uniform, sinusoidal magnetic field of known strength and frequency. In addition, we present a novel exposure technique based on a standard organ culture dish containing two circular, concentric annular rings. Exposure of the organ culture dish to a uniform magnetic field induces different average electric fields in the liquid medium in the inner and outer rings. Results of experiments with this system, which were reported in a separate paper, have shown the dominant role of the magnetically induced E field in producing specific biological effects on cells, in vitro. These results emphasize the need to report data about the induced E field in ELF in-vitro studies, involving magnetic field exposures. Our data tables on E and J in standard containers provide simple means to enable determination of these parameters. PMID- 1590819 TI - An integrated ELF magnetic-field generator and incubator for long-term in vitro studies. AB - Long-term studies of the effects of low-frequency magnetic fields on cells in culture require an incubator that is free of contaminating magnetic fields and that provides automatic control of exposure duration, uniform applied fields, a uniform and well-controlled environmental temperature, and high reliability of the total system. We describe a dual-incubator system in which the enclosed solenoid of either unit can provide a sham exposure while the other generates a magnetic induction of up to 500 microT. Each solenoid-incubator unit contains an enclosed rack that can hold as many as 140 petri dishes for culturing cells; each unit is heated radiantly by circulating warm water. Field-exposure conditions and temperatures are continuously monitored and controlled by a microcomputer. PMID- 1590820 TI - Measurement of magnetically induced electric fields in conductive media near a 60 Hz current-carrying wire. AB - Electric fields induced in a conductive body by the magnetic field of a current carrying wire were analyzed theoretically and experimentally to assess the dosimetric importance of highly nonuniform, field-exposure conditions. Experimentation revealed that a 60-Hz magnetic field was inversely proportional to the radius of a wire bundle carrying 100 A within a 0.5-m2 test area. A miniaturized electric field probe was used to measure the electric fields induced in 5-cm-deep, saline-filled models. In the theoretical analysis, numerical estimates of induced fields were made by a spreadsheet method. The theoretical calculations and the measured values of induced electric fields were generally in good agreement. The induced fields were in a plane perpendicular to a vertically incident magnetic field; the maximally induced fields were in areas nearest the wire bundle. The strength of the induced field increased with model size: from 96 microV/cm in a 10 x 10 cm model to 176 microV/cm in a 40 x 40 cm model. The strength of the field induced in a 20 x 20 cm model decreased with increasing model-to-wire spacing: from 132 microV/cm for a 1-cm spacing (2-mT maximum, incident field) to 50 microV/cm for a 6-cm spacing (0.33-mT maximum). The results indicate that increases in local values of nonuniformly incident fields produce relatively small increases in induced electric fields. This finding may be important in dosimetric consideration of circumstances, such as use of electric blankets, in which fields of low average strength are accompanied by intense local fields. PMID- 1590821 TI - Development of chicken embryos following exposure to 60-Hz magnetic fields with differing waveforms. AB - Previous studies in my laboratory have revealed a reproducible and statistically significant increase in the number of malformations in live chicken embryos that had been exposed during the first 48 h of incubation to a pulsed magnetic field (unipolar pulses, 100-pps, 1-microT peak density). In marked contrast, no adverse effect was seen following similar exposure to 60-Hz, bipolar, unipolar, or split sine waves at 3-microT peak-to-peak. In the four experiments comprising the present study, differences in the numbers of malformations between control and experimental groups were not statistically significant. Field-free incubation for an additional 72 h after exposure to a bipolar sine wave for 48 h resulted in an increase in normal live embryos in both control and treated groups. PMID- 1590822 TI - Criticism of Lednev's mechanism for the influence of weak magnetic fields on biological systems. AB - V. V. Lednev has proposed a mechanism that he suggests would allow very weak magnetic fields, at the cyclotron resonance frequency for Ca2+ ions in the earth's field, to induce biological effects. I show that for four independent reasons no such mechanism can operate. PMID- 1590823 TI - Neutral glycosphingolipid content and composition of cells from normal and atherosclerotic human aorta. AB - We have investigated the content and composition of neutral glycosphingolipids (GSLs) in the cells isolated by enzyme digestion from elastic-hyperplastic and musculo-elastic intimal layers of grossly normal and atherosclerotic regions of human aorta. We have detected three types of neutral GSLs in the intimal cells identified as glucosylceramide, trihexosylceramide and tetrahexosylceramide. We failed to detect lactosylceramide in the intimal cells. The cells of the elastic hyperplastic layer of grossly normal regions contained trihexosylceramide and tetrahexosylceramide, while glucosylceramide was not detected. Considerable amounts of glucosylceramide were found, and the trihexosylceramide and tetrahexosylceramide content was increased in the cells isolated from atherosclerotic regions. The cells of the musculo-elastic layer of grossly normal intimal regions contained glucosylceramide, trihexosylceramide and tetrahexosylceramide. Cells of the musculo-elastic layer of the fatty streak contained noticeable higher amounts of glucosylceramide, as well as greater amounts of trihexosylceramide and tetrahexosylceramide. Cells of the musculo elastic layer of the plaque also appeared to contain more glucosylceramide, tetrahexosylceramide, but less trihexosylceramide as compared with grossly normal regions. In both cases cells of the fatty streak exhibited the highest total amount of neutral GSLs, but at the same time the neutral GSL composition of the fatty streak was not similar to GSL composition which is known for human blood monocytes. These findings indicate that elevation of neutral GSL level is observed in cells from atherosclerotic lesions of human aortic intima. PMID- 1590824 TI - Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size. AB - Oxidative modification of low density lipoproteins (LDL) has been implicated in the sequence of events leading to fatty streak formation in the arterial intima. Increased oxidative modifications of dense versus buoyant LDL particles could contribute to increased atherosclerosis associated with lipoprotein profiles enriched in small, dense LDL. In the present studies, we compared rates of copper induced oxidative changes for six LDL subfractions ranging in density from 1.023 to 1.053 g/ml and mean particle diameter from 282 +/- 10 to 245 +/- 3. Rates of formation of thiobarbituric acid-reactive substances (TBARS), as indicated by the time required for half-maximal TBARS formation (T1/2max), decreased with increasing density and decreasing particle diameter to a minimum in fraction 5 (d = 1.046 g/ml, diameter = 250 +/- 5) (P = 0.007). In parallel studies using unfractionated LDL (d = 1.019-1.063 g/ml), T1/2max values were inversely correlated with the predominant LDL species diameter as determined by 2-16% gradient gel electrophoresis (P less than 0.05), consistent with the involvement of subclass composition in determining oxidative behavior. In separate experiments, subfraction differences in oxidation rates as assessed by TBARS formation were verified by the finding of similarly dispartate changes in fluorescence intensity and anionic electrophoretic mobility. T1/2max values were not related to LDL contents of alpha-tocopherol, beta-carotene, protein, triglycerides or phospholipids, but were significantly correlated with unesterified cholesterol content (r = 0.46; P less than 0.001) and were inversely associated with cholesteryl ester content (r = 0.28; P less than 0.05). The positive association of T1/2max with unesterified cholesterol suggests that this constituent may impart resistance to oxidative modification, possibly by altering properties of the surface monolayer where it resides. PMID- 1590825 TI - Metabolism of intestinal triglyceride-rich lipoproteins in the genetically hypercholesterolemic rat (RICO) AB - Experiments were carried out to compare the catabolism of intestinal lipoproteins between genetically hypercholesterolemic (RICO) and normocholesterolemic (SW) rats. Kinetics of plasma cholesteryl ester were studied after injection of cholesterol-labeled chylomicrons or VLDL. The chylomicron clearance is reduced in the RICO rat (rate constant, K = 7.2 +/- 0.1 h-1 vs. 10.7 +/- 0.1 h-1 in SW rat), while a much more minor alteration was observed in the catabolism of lymph VLDL (K = 4.3 +/- 0.6 h-1 in the RICO rat vs. 5.1 +/- 0.4 h-1). The injection of chylomicrons from SW rats to RICO rats and from RICO rats to SW rats showed that the fall in the rate of catabolism of chylomicrons in RICO rats was not secondary to an increase in the production rate, but was related to the lipoprotein particle itself without any alteration of the catabolic system. The reduction in the rate of catabolism of chylomicrons in the RICO rat could be related to a change in their apolipoprotein composition (increase in the proportion of apolipoprotein E = 12 +/- 2% vs. 3 +/- 1% in the SW rat). PMID- 1590826 TI - Effect of spontaneous pathology and thrombin on leukocyte adhesion to rat aortic endothelium. AB - Leukocyte adhesion and other injury parameters have been studied in the aortic endothelium of Sprague-Dawley rats in two situations: (1) spontaneous pathology in conventional rats with antibodies to Mycoplasma pulmonis and/or Kilham or Sendai viruses, and (2) intravascular coagulation by thrombin administration in SPF rats. Adhesion (esterase (+) leukocytes/mm2) in SPF rats was 8 +/- 5 (n = 12). Adhesion in 38% of the conventional rats was 54 +/- 27 (n = 8), half of them being non-analyzed and the rest having antibodies to M. pulmonis and/or Kilham rat virus. In 19 rats with antibodies to M. pulmonis and/or Kilham or Sendai viruses, AgNO3 and hematoxylin staining of the aortic endothelium showed an increase in leukocyte adhesion, and the presence of argyrophilic cells, stigmata and granularity--severe endothelial lesions being observed in some cases. Adhesion in rats after 0.25, 1, 3 and 6 h of thrombin administration (30 units/100 g) was not different from controls. Adhesion after 24 h was 108 +/- 53 (n = 10) and 60 +/- 59 (n = 10), and 22 +/- 20 (n = 10) in rats treated with thrombin plus heparin or hirudin, respectively. Thrombin produced endothelial lesions at all times studied, and these included membrane blebs, platelet and erythrocyte adhesion and alterations in the pattern of endothelial esterase activity. PMID- 1590827 TI - Association of N-glycosylation of apolipoprotein B-100 with plasma cholesterol levels in Watanabe heritable hyperlipidemic rabbits. AB - We have previously demonstrated the heterogeneity of N-linked sugar chains of apolipoprotein (apo) B-100 in Watanabe heritable hyperlipidemic (WHHL) rabbit and fasting Japanese White rabbits (Arteriosclerosis, 10 (1990) 386-393). To investigate further the role of N-linked sugar chains of apo B-100 in lipid metabolism, we examined the correlation between the N-glycosylation of apo B-100 and serum cholesterol levels in WHHL rabbits. The N-linked sugar chains of apo B 100 were liberated by hydrazinolysis, followed by NaB3H4 reduction and were fractionated by paper electrophoresis and BioGel P-4 column chromatography. These were found to consist of one neutral (N) and two acidic fractions (A1 and A2). N contained a high mannose type oligosaccharide consisting of Man5.GlcNAc2 to Man9.GlcNAc2, while A1 and A2 contained monosialylated and disialylated complex type oligosaccharides, respectively. The molar ratio varied among the 5 WHHL rabbits. There was an inverse correlation between the ratio of acidic oligosaccharide fractions (A1 + A2) and serum cholesterol levels (r = -0.971, P less than 0.01) in the 5 WHHL rabbits. These results indicate that the N glycosylation of apo B-100 is closely related to cholesterol metabolism in WHHL rabbits. PMID- 1590828 TI - Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non diabetic subjects. AB - Utilising a combination of m-aminophenyl-borate affinity chromatography and an immunoradiometric assay for apolipoprotein B (apo B), we have developed a specific and highly sensitive (6 ng/ml) procedure for the assay of glycated apo B. We studied 52 diabetic patients, 50 non-diabetic control subjects and 12 patients heterozygous for familial hypercholesterolaemia (FH). Both insulin dependent and non-insulin dependent diabetics were included in our study. Total apo B in the diabetics (108 +/- 5 mg/dl; mean +/- S.E.M) was increased (controls: 95 +/- 4 mg/dl; P less than 0.05). In the FH group the serum apo B concentration (216 +/- 24 mg/dl) was significantly higher (P less than 0.001) than both the other groups studied. Both the serum glycated apo B concentration (9.3 +/- 0.8 mg/dl versus 4.8 +/- 0.7 mg/dl) and the percentage glycated apo B (7.9 +/- 0.4% compared to 3.9 +/- 0.2%) were significantly higher in the diabetics than in non diabetic controls (P less than 0.001). A positive correlation was found between the percentage of glycated apo B and glycated haemoglobin (r = 0.65; P less than 0.001) and fasting glucose concentration (r = 0.52; P less than 0.001) in diabetics. The percentage of glycated apo B in FH patients was not significantly different from controls, but the serum concentration of glycated apo B, because of the greatly increased total level of apo B was raised (8.2 +/- 1.4 mg/dl) to a similar extent to that of the diabetics. PMID- 1590829 TI - Macrophage colony stimulating factor prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits. AB - The early atherosclerotic lesion is characterized by the presence of macrophage derived foam cells. Macrophage colony stimulating factor (M-CSF) specifically stimulates the functions of the monocyte-macrophages. To elucidate the effects of M-CSF in the atherogenic process in vivo, we administered human recombinant M-CSF into Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Three hundred micrograms of M-CSF were intravenously injected into WHHL rabbits aged 2.5 months, three times a week for 8.5 months. After the M-CSF treatment, we found very retarded progression of atherosclerosis. The accumulation of cholesterol ester was remarkably decreased in the aortae of M-CSF-treated animals (0.60 +/- 0.32 mg/g tissue), as compared to those of controls (4.32 +/- 0.61 mg/g tissue). Furthermore, the percentage of the surface area of the aorta with macroscopic plaque in animals treated with M CSF was 14.3 +/- 6.2%, much less than that in controls receiving saline injection (38.8 +/- 8.0%). Thus, M-CSF definitely prevented the progression of atherosclerosis in WHHL rabbits by influencing macrophage functions. PMID- 1590830 TI - Hemostatic risk factors in patients with vascular disease. PMID- 1590831 TI - Increased plasma concentration of endothelin-1 in cholesterol-fed rats. PMID- 1590832 TI - Propofol and malignant hyperthermia. PMID- 1590833 TI - And nor are we. PMID- 1590834 TI - A human issue. PMID- 1590835 TI - Safety of alfentanil. PMID- 1590836 TI - A medical practice opinion program. PMID- 1590837 TI - A comprehensive health care directive in a home for the aged. PMID- 1590838 TI - Suggested standards for reporting on arterial aneurysms. PMID- 1590839 TI - Overseas medical practitioners and "racial discrimination". PMID- 1590840 TI - Fetal fibronectin and preterm labor. PMID- 1590841 TI - Re: "Age at onset as an indicator of familial risk of breast cancer". PMID- 1590842 TI - The work of breathing through large-bore intravascular catheters. PMID- 1590843 TI - Dogs that bite. PMID- 1590844 TI - Dundee coronary risk-disk. PMID- 1590845 TI - Potassium concentrations in irradiated blood. PMID- 1590846 TI - The health strategy. PMID- 1590847 TI - Posterior circulation dissections. PMID- 1590848 TI - Access to genetic sequence data. PMID- 1590849 TI - Human origins and analysis of mitochondrial DNA sequences. PMID- 1590850 TI - The postcricoid impression on the esophagus. PMID- 1590851 TI - Insomnia in the elderly. PMID- 1590852 TI - Toradol caution in the aspirin-sensitive. PMID- 1590853 TI - Anemia of chronic disease: a misnomer? PMID- 1590854 TI - T-cell subsets in drug-induced toxic epidermal necrolysis. PMID- 1590855 TI - Vision screening in preschool children. PMID- 1590856 TI - Urinary incontinence. PMID- 1590857 TI - IQ and diet. PMID- 1590858 TI - Tips for death investigations. PMID- 1590859 TI - Gay teens and suicide. PMID- 1590860 TI - Weight and menstrual function in patients with eating disorders and cystic fibrosis. PMID- 1590861 TI - Use of furosemide in patients with syndrome of inappropriate antidiuretic hormone secretion. PMID- 1590862 TI - Hypothermia revisited. PMID- 1590863 TI - Pregnancy complicated by carcinoma of the colon above the rectum. AB - Although rare during pregnancy, colorectal carcinoma is one of the leading three types of cancer in women. In the medical literature, there are only 28 reports of carcinoma of the colon above the rectum concurrent with pregnancy. During the last 8 years in our community, four pregnant women have received care by us for this usually lethal disease. These cases are presented and the pertinent considerations of this pregnancy complication based on the entire collected experience are reviewed. The possibility of this disease must be considered in the obstetric as well as the gynecologic patient. PMID- 1590864 TI - Fetal rhabdomyoma: a prenatal echocardiographic marker of tuberous sclerosis. AB - Little is known about the intrauterine course of tuberous sclerosis (TS) and the fetal age at which specific abnormalities may be detected. A case of neonatal TS diagnosed prenatally by the echocardiographic finding of a cardiac rhabdomyoma is presented. Literature review revealed that 50% of prenatally diagnosed rhabdomyomas are asymptomatic. Although cardiac rhabdomyomas tend to regress during the first year of life, they may for months be the only manifestation of TS. The number of new mutations may have been overestimated. The combination of computed tomography, echocardiography, and renal sonograms allows for the detection of other family members with latent TS. The incidence of TS in cases of cardiac rhabdomyomas is probably higher than previously reported. PMID- 1590865 TI - An attempt to quantify characteristics of behavioral states. AB - In order to describe fetal behavior in detail, 44 pregnant women were examined longitudinally between 34/0 to 42/0 gestational weeks; the traces of 38 fetuses were included for further analysis. We used two ultrasound scanners and an actocardiography and registered the number and duration of fetal head, trunk, limb, breathing, and eye movements (FEM) as well as the fetal heart rate (FHR). Data were recorded on polygraphic tracings and analyzed off-line via a 1-minute moving window. Percentile ranges were calculated throughout the observation period. Four primary behavioral states were analyzed according to Nijhuis et al. but state 3F could be neglected in our data. FHR variability, slow and rapid FEM, and the number of movements were most significant in differentiating between states 1F, 2F, and 4F. By considering percentile values of single parameters, the differentiation of states, a computer analysis, and the recognition of compromised fetuses might be facilitated. PMID- 1590866 TI - Treatment of persistent postpartum HELLP syndrome with plasmapheresis. AB - Thrombocytopenia, associated with microangiopathic disease, is one characteristic of severe preeclampsia. Thrombocytopenia and intravascular hemolysis usually resolve by postpartum days 4 to 5. When thrombocytopenia secondary to microangiopathic disease persists, plasmapheresis may be used to arrest and reverse the process. Three patients over a 24-month period were successfully treated with plasma exchange with fresh frozen plasma. Several investigators who have cared for patients with persistent thrombocytopenia associated with preeclampsia have concluded that early plasmapheresis may be useful therapy. Plasma exchange should also be considered as a therapeutic option when clinical deterioration occurs due to microangiopathic disease. PMID- 1590867 TI - Clinical significance and sonographic diagnosis of velamentous umbilical cord insertion. AB - In order to evaluate the clinical significance of velamentous cord insertion (VCI) and the role of ultrasound in its diagnosis, all 82 cases of VCI during January 1985 to January 1989 at the Mount Sinai Medical Center were reviewed. The overall rate of VCI in our study (0.5%) was similar to that of previous reports. Pregnancy outcomes in VCI patients with 77 singleton gestations were compared with a control group of 15,865 patients. In contrast to the existing literature, multiparity and prior cesarean section deliveries were not increased in pregnancies with VCI. The VCI group had more intrapartum complications and a lower birthweight than the controls. Routine nontargeted obstetric ultrasound failed to detect any cases of VCI, including three cases of vasa previa. Since VCI was not identified prenatally and many of its sequelae are readily identifiable only during the intrapartum period, the potential for preemptive obstetric intervention appears to be limited. In addition, failure to diagnose apparent VCI during a routine ultrasound does not appear to be a departure from the standard of care. PMID- 1590868 TI - Prenatal sonographic findings of massive lower extremity lymphangioma. AB - A massive lymphangioma was detected sonographically in the lower extremity of a fetus at 28 weeks' gestation. On ultrasound study, the mass had multiple cysts and extended from the left lower abdomen to the left knee. The differential diagnosis and obstetric management following prenatal diagnosis of a fetal lower extremity mass are presented. PMID- 1590869 TI - Cardiopulmonary resuscitation in very low birthweight infants. AB - Of 191 patients with birthweight less than 1500 gm admitted to our neonatal intensive care unit in a 2-year period, 41 underwent cardiopulmonary resuscitation (CPR). Eleven of 41 very low birthweight (VLBW) (27%) survived to be discharged. None of the infants who received CPR after 72 hours of life survived. Also, all infants who underwent CPR, both in the delivery room and neonatal intensive care unit (NICU), died. The most significant factor distinguishing survivors from nonsurvivors was the demonstration of vasopressor unresponsive hypotension 20 hours prior to CPR in the latter group. This study confirmed the very poor survival rate after CPR in VLBW infants. We conclude that performance of CPR in patients with vasopressor unresponsive hypotension or previous delivery room resuscitation should be considered a rescue or experimental treatment and parents should be given the option of no resuscitation. Future research efforts should be directed to better the understanding and treatment of cardiovascular dysfunction prior to cardiac arrest. PMID- 1590870 TI - The effects of pH and osmolality on bacterial growth in amniotic fluid in a laboratory model. AB - In studying the effects of amniotic fluid on bacterial growth in a laboratory model, we noted that the pH of the fluid appeared to exert an independent effect. This study was designed to test the ability to control the growth of Escherichia coli in amniotic fluid simply by controlling two important growth conditions, pH and osmolality. The effects of pH and osmolality on growth of E. coli were systematically studied in a standard media and in amniotic fluid. Optimal ranges in standard media were pH of 5.6 to 6.6 and osmolality of 150 to 215 mOsm. When the results of growth at 24 hours were corrected for pH by analysis of covariance, the presence of amniotic fluid or phosphate had no effect. We found pH to be the only variable predictive of bacterial growth in amniotic fluid in this laboratory model. PMID- 1590871 TI - Long distance perinatal transport. AB - Mortality, incidence of intraventricular hemorrhage (IVH), and complications were evaluated in a perinatal transport system involving patient movement over distances from 1500 to 3700 km over a 3-year period. Of 179 transports, 60% involved neonatal transport, and 58% of the transports involved infants delivering at 32 weeks' gestation or less. Mortality rates were similar between inborn, maternal, and neonatal transports with a trend toward improved survival in all inborn infants 1000 gm or less at birth. IVH occurred in 32% of infants 32 weeks or less gestation; a higher incidence of grades III/IV bleeding were seen in transported infants between 1001 and 2000 gm compared with maternal transports and all inborn infants. Complications occurred in 20% of transports. The frequency of complications were significantly lower when transport was accomplished by the Level III team. In utero transport of selected high-risk pregnancies is preferred despite the ability to provide safe, effective transport of ill neonates over extremely long distances. PMID- 1590872 TI - Prostaglandin E2 gel induction of patients with a prior low transverse cesarean section. AB - To determine safety and efficacy of induction with prostaglandin E2 gel, we compared the outcome of 25 patients (study group) with an unfavorable cervix, a medical indication for delivery, and one prior low cervical transverse cesarean section to 56 patients (comparison group) with one prior low cervical transverse cesarean section and spontaneous labor. We placed 1 mg of prostaglandin E2 in gel intracervically in the 25 study patients. Common indications for delivery were: diabetes, post dates, and preeclampsia. Although most labor and delivery variables were similar, the study group had a longer mean latent phase (14.2 +/- 13.8 versus 7.3 +/- 3.7 hours: p less than 0.002), but had a shorter mean length of active phase (4.0 +/- 3.5 versus 5.7 +/- 3.0 hours; p less than 0.02). None of the patients in either group had a dehiscence of the uterine scar, nor rupture of the uterus. Both groups had a similar cesarean section rate. Since from the few reported, nonrandomized studies it appears that prostaglandin E2 gel use in patients with a prior low cervical transverse cesarean section may be useful and relatively safe, it may be time to attempt randomized trials of prostaglandin E2 gel versus oxytocin for induction of patients with a prior low cervical transverse cesarean section, unfavorable cervix, and a medical indication for delivery. PMID- 1590873 TI - Fused eyelids in the extremely premature infant: multivariate analysis of survival and outcome. AB - The presence of fused eyelids at birth in the extremely low birthweight infant (less than 1000 gm) is often regarded by physicians as an indication of nonviability. This is especially true for the pediatrician who does not have routine exposure to extremely premature infants and may use the presence of fused eyelids to influence the level of resuscitation afforded the infant in the first crucial minutes following birth. Unfortunately, there are scant data in the literature to guide general pediatricians with regard to this issue. The purpose of this study was to examine, with the aid of multivariate statistical analysis, the survival and combined outcome score in extremely premature infants with and without fused eyelids. The combined outcome was a composite of several outcome variables (intraventricular hemorrhage, bronchopulmonary dysplesia, and retinopathy of prematurity); survival was defined employing the standard definition of neonatal survival, that is, alive at 28 days post natal age. Combined outcome and survival were analyzed with regard to several independent variables (birthweight, gestational age, and 5-minute Apgar scores, mode of delivery, race, sex, and maternal age). A regression analysis was performed to determine the effect of the independent variables on the combined outcome. A separate multivariate logistic regression analysis was employed to determine the effect of the same independent variables on neonatal survival.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590874 TI - Diabetes mellitus in pregnancy and periconceptional genetic counseling. AB - Gestational diabetes constitutes 90% of all pregnant diabetic patients, whereas insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) together account for the remaining 10%. Diabetes is considered a heterogeneous disease with a continuous spectrum between IDDM and NIDDM. It is believed that gestational diabetes is also a heterogeneous disorder representing, at least in part, patients who are destined to develop in later life either IDDM or NIDDM. Studies in identical twins have shown clear-cut differences in the genetic inheritance of IDDM and NIDDM. Nearly 100% of identical twins were found to be concordant for NIDDM; whereas in IDDM the concordance rate ranges between 20 and 50%. This concordant pattern indicates a higher genetic contribution in NIDDM than IDDM. Furthermore, IDDM is an HLA-linked disorder, and NIDDM is not. The exact mechanism of inheritance of IDDM and NIDDM is not known; therefore the information used in genetic counseling is based on empirical risk estimates. Recent information demonstrates that IDDM is transmitted less frequently to the offspring of diabetic mothers than diabetic fathers (1.3% versus 6%). The estimated risk of recurrence of IDDM to offsprings with one already affected sibling and unaffected parents is 5 to 6%. Additionally, the empirical risk of NIDDM first-degree relatives developing diabetes is much higher than the observed in IDDM relatives, 15% for first-degree relatives and 60 to 75% when both parents have NIDDM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590875 TI - Uteroplacental Doppler flow velocity waveform indices in normal pregnancy: a statistical exercise and the development of appropriate reference values. AB - In a prospective cross-sectional study, we examined 154 normal pregnant women and measured the systolic to diastolic (S/D) ratio and resistance index (RI) in the umbilical artery and both uterine arteries. Placental location with respect to laterality was determined by real-time ultrasound. In patients with unilateral placental location, each uterine artery was evaluated according to its relationship with the placenta. Doppler flow velocity waveforms were obtained by a continuous wave Doppler device. Kolmogorov D tests revealed that RI values follow gaussian distribution, but that S/D values were markedly skewed to the right. There was a significant negative linear relationship between gestational age and umbilical artery RI and a significant negative curvilinear relationship between gestational age and umbilical artery (S/D (r = 0.83, p less than 0.001; and r = -0.79, p less than 0.001, respectively). Confidence bands for umbilical artery RI were developed based on the linear model with gestational age (fitted umbilical artery RI = 0.97199 - 0.01045*gestational age). Confidence bands for umbilical artery S/D were derived from the corresponding RI values by means of the functional relationship S/D = 1/(1 - RI). The RI and S/D values of the uterine arteries declined until 24 to 25 weeks' gestation and remained unchanged thereafter. This relationship, however, was not statistically significant (r = 0.10, p = 0.22). The placental uterine artery is different from the nonplacental quantitatively and qualitatively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590876 TI - Comparative studies on thermoregulatory responses to heat between Japanese Brazilians and Japanese. AB - Eight male Japanese Brazilians (20-32 yrs) and 11 male Japanese (22-24 yrs) volunteered for this study. The Brazilians had been staying for about 2-21 weeks in Japan. Their physical characteristics are not significantly different from those of the Japanese. Each one of them sat on a chair for 45 min at 40 degrees C (R.H. 50%) in a climatic chamber. Then, they exercised using a bicycle ergometer in a semi-reclining position for 45 min at 40% of maximal oxygen uptake. Forearm blood flow (FBF), oxygen uptake (VO2), heart rate (HR), skin temperature (Tsk), sweat rate (SR) at chest region and body weight loss (delta Wt) were measured. Thermal sensation and thermal comfort were also measured. Thermal and comfort sensation confirmed that Japanese Brazilians felt cooler and more comfortable in 40 degrees C environment than the Japanese. VO2, SR and delta Wt for both groups were not significantly different. FBF and HR for Brazilians were significantly lower than those for Japanese. Tsk at chest region for Brazilians was found to be significantly higher than that for Japanese. Thus the thermoregulatory responses observed in Japanese Brazilians may be largely attributed to the climate in their native places located on the Tropic of Capricorn. PMID- 1590877 TI - [Dietetics of SCUBA diver]. PMID- 1590878 TI - [Physiological anthropology in Japan]. AB - In the history of about 100 years of anthropology in Japan, studies of physiological anthropology have made very important contributions from the standpoint of physiological function of mankind. The activity of physiological anthropology in Japan has started systemically November 1978 when the study group was organized under Prof. Keiichi Yoshida as the president and the first meeting was held in February 1979. The study group has developed to Research Society of Physiological Anthropology (President Prof. Keiichi Yosida, October 1982) and then reorganized as Society of Physiological Anthropology (President Prof. Masaro Kaji, Kurume University School of Medicine, April 1987). An increase of members of the Society from 122 in 1982 to 570 in 1991 suggests the prosperity of the study in this field. The Society has two meetings every year since 1979 and the 27th meeting was held last October. The Annals of Physiological Anthropology is published quarterly (will be published bimonthly from 1992) since 1983 and about 300 papers including 116 original articles have been reported. The Annals covers the following fields: Clothing and thermal physiology, Living in normal and abnormal environment, Nutrition and morphology, Sports physiology and medicine, Work physiology, Ergonomics, General physiology and others. In recent progress of science, study in physiological anthropology must respond to various environments in every field of living. The future of physiological anthropology was discussed in the situation of rapidly changing patterns of human life in Japan. PMID- 1590879 TI - [Evaluation of mental workload of short-term memory task by secondary task performance and frontal midline theta rhythm]. AB - The purpose of the present study was to evaluate the mental workload of short term memory task by two objective measures, the secondary task performance and the frontal midline theta rhythm (Fm theta) of the electroencephalogram (EEG). First, to choose Fm theta appearance subjects EEGs were recorded for 18 male students during performing additional task. On Fm theta appearance subjects (8 males) a series of short-term memory task with changed number of memorable figures was imposed as the primary task, and tracking task as the secondary task. The task that presents seven numbers will be over the subjects' limits of short term memory, and it was the threshold that the subjects' mental workload will be increased. PMID- 1590880 TI - [Detection of HIV in donated blood]. PMID- 1590881 TI - [Transfusion and Jehovah's Witnesses]. PMID- 1590882 TI - [Standardization trial of ABO-Rh(D) blood typing using a U-microplate]. AB - This study reports the results of ABO-Rh (D) typing in microplate according to a suggested protocol. 35,532 blood typings were performed by 13 laboratories, compared to usual technics. This work has proved the feasibility in routine of this protocol in order to identify the A, B, D and weak antigens. However the difficulties in detecting some weak variants reveal the interest of standards for immuno-haematology reagents, to apply in the microplate technology. PMID- 1590883 TI - [Ultimate controls involving the recipient of transfused products]. AB - It is difficult for blood transfusion centers to validate the link blood products receiver because of two reasons: most of transfusional acts are performed outside of transfusion centers; information feed-back is not perfect: data processing is completed by someone who has not carried out the transfusion. Therefore, the error risk is higher and it is impossible to enter data on transfusion reactions. The solution is the direct data storage just before transfusion and the computerized transmission to the system containing transfusion index cards. The necessary computerization is not constraining for the users: the portable computer is perfectly autonomous, not very cumbersome, light and reliable. The use of bar codes optimizes the security of the process making is possible to get a line donor-donation-analysis-blood products-receiver and to follow the trace of blood products. PMID- 1590884 TI - [Immunoglobulin genes and the origin of antibody diversity]. AB - The genes encoding for the heavy, Kappa and Lambda chains of immunoglobulins are located on separate chromosomes. Each gene consists of many segments encoding for variable (V) and constant (C) domains of immunoglobulins. Each V gene is assembled from individual segments of germline, VL and JL for the light chains, VH, D and JH for the heavy chains. There are several hundreds VH and VL segments and a small number of D and JH segments. A complete VH gene (VH-D-JH combination) is first expressed in association with the nearest C region gene (C mu) but a class switch recombination may occur, enabling the same VH to associate with C regions of gamma, alpha or epsilon type. The generation of the antibody diversity is explained by several mechanisms: a) the rearrangements of the segments encoding for the variable domains (related to the presence of many segments and the joining variability between these segments); b) the combinations between heavy and light chains; c) the occurrence of somatic mutations in the DNA encoding for VH and VL gene segments. PMID- 1590885 TI - [Transformation of [5'-3H]riboflavin into 5,6-dimethylbenzimidazole]. AB - The 5,6-dimethylbenzimidazole unit of vitamin B12 is formed from riboflavin via FMN in aerobic and some aerotolerant bacteria. Thereby C-1' of the ribityl side chain gets C-2 of 5,6-dimethylbenzimidazole. Experiments with homogenates of Propionibacterium shermanii on the fate of C-atoms 2' to 5' of the ribityl side chain of riboflavin in this transformation are reported. It was found that [5' 3H]riboflavin leads to radioactive sugar phosphates. These were isolated, dephosphorylated, and separated. Thus 3H-D-fructose and 3H-D-glucose were detected. The degradation of 3H-D-glucose revealed that 14 per cent of the total radioactivity was located in C-1, and 86 per cent in C-6. This indicates that during 5,6-dimethylbenzimidazole biosynthesis a three carbon unit is formed from the ribityl side chain of riboflavin. PMID- 1590886 TI - Odor-structure relationships in n-hexenols and n-hexenals. AB - The relationships between the chemical structures and the odor characteristics were examined on a series of highly purified n-hexenols and n-hexenals-(14 isomers). The C6-enals and the corresponding alcohols resembled in odor characteristics each other. However, the odor strength of the aldehydes was 100 1000 times higher than those of the alcohols. In the principal components analysis, the position of carbon-carbon double-bond in the C6-compounds was closely related to the scores of the first principal component, whereas the functional groups, hydroxy and formyl groups, were related to those of the second principal component except for (Z)-3-hexenol. PMID- 1590887 TI - Reaction mechanism of protocatechuate 3,4-dioxygenase. AB - We have observed that high SOD-like function (decomposition of superoxide anion) was observed for several iron(III) compounds with tripodal ligands and several oxovanadium(IV) compounds, and also that these compounds exhibit high catalytic activity for oxidative cleavage of 3,5-di-tert-butylcatechol in non-donating solvents such as dichloromethane or nitromethane. These are suggesting that the same reaction intermediate exists in reaction mixtures of both the SOD-like and catecholase-like functions of these compounds. Based on these facts, we have proposed a new reaction mechanism for the oxidative cleavage of catechol catalyzed by the native non-heme iron dioxygenases; this includes formation of an iron(III)-peroxide adduct as a reaction intermediate, which exhibits electrophilic nature. PMID- 1590888 TI - Formation of ssb, dsb, and uracil in monofilarly and bifilarly bromouracil substituted DNA molecules. AB - Bifilarly BU-substituted ColE 1 plasmid and monofilarly BU-substituted M 13 phage DNA were irradiated with UV light of 313 nm. Using agarose gel electrophoresis and "reversed phase" HPLC technique ssb, dsb induction and uracil formation, respectively, could be detected in the irradiated DNA in dependence on the UV fluence. The analysis of the strandbreaks in bifilar ColE 1 DNA shows a significant part of directly induced dsb. Cross sections of ssb induction from 4.1 m2/J x 10(7) in 28%, 3.9 m2/J x 10(7) in 55% and 3.1 m2/J x 10(7) in 85-90% BU-substituted DNA were calculated. The cross section for dsb induction was found to be 0.04 m2/J x 10(7), estimated from the linear part of the fluence effect curve. In monofilar M 13 DNA a linear fluence effect curve for dsb induction was obtained. Excluding other than the direct production of dsb by using an in vitro approach for M 13 DNA, the results strongly support the hypothesis that dsb can be induced by one photochemical absorption event. The cross section for ssb was 3.8 m2/J x 10(7) and for dsb 0.05 m2/J x 10(7) in 41.5% monofilarly BU substituted M 13 DNA. The comparison of ssb, dsb, and uracil production in bifilar and monofilar DNA with similar BU substitution showed no significant difference between the two DNA systems (ColE 1, M 13), indicating that the location of BU molecules in one or in both DNA strands will not lead to a different number of lesions after UV313 exposure. PMID- 1590889 TI - Protective effects of phenolic compounds on CCl4-induced toxicity in isolated rat hepatocytes. AB - The protective effects of a series of phenolic compounds, phenolic acids and flavonoids on the cytotoxicity of CCl4 in rat hepatocytes were studied. A number of flavones, 7,8-dihydroxy-flavone, luteolin and hypolaetin-8-glucoside, flavonols, morin, quercetin, robinetin and gossypin, phenolic acids, gallic, caffeic and chlorogenic acids, as well as the flavane (+)-catechin significantly inhibited alanine amine transferase (ALT) release. Catechol groups are determinant for the protective activity of flavonoids and cinnamic acid derivatives, as well as the resorcinol or pyrogallol moieties in the B ring of flavonoids. In benzoic acid derivatives a pyrogallol group is required. This feature is associated with the inhibition of ALT spontaneous release. PMID- 1590890 TI - Action of brassinosteroids on the epithelial cell line from Chironomus tentans. AB - The two brassinosteroids, 22 S,23 S-homobrassinolide and 22 S,23 S homocastasterone are weak competitors of the binding of [3H]ponasterone A to the intracellular ecdysteroid receptor from the epithelial cell line from Chironomus tentans. The relative affinities to the ecdysteroid receptor are 0.001 for both brassinosteroids as compared to 20-OH-ecdysone and 0.1 in comparison to ecdysone. Both substances exert morphological effects similar to those observed with 20-OH ecdysone. Like moulting hormones both brassinosteroids inhibit chitin synthesis. However, these effects were observed only at rather high concentrations (10(-5) to 10(-4) M) which were cytotoxic for 22 S,23 S-homobrassinolide. PMID- 1590891 TI - The effect of neuropeptides on the ERG of the crayfish Orconectes limosus. AB - CCAP (Crustacean Cardioactive Peptide), Proctolin, FMRFamide, Met- and Leu enkephalin, Substance P, RPCH (red pigment concentrating hormone) and PDH (pigment dispersing hormone) were applied to the isolated retina of the crayfish Orconectes limosus. Changes in light sensitivity, measured as changes of the amplitude of the electroretinogram (ERG) were observed after application of RPCH, PDH and CCAP. RPCH caused an increase of the ERG amplitude to 133% of its reference value whereas PDH and CCAP decreased the amplitude to 78% and 30% respectively. A dose-response curve showed that 10(-9) mol/l CCAP produce a half maximal effect. PMID- 1590892 TI - Relative affinities of nucleotide substrates for the yeast tRNA gene transcription complex. AB - Apparent Michaelis constants for nucleotides in transcription of yeast tRNA gene by homologous RNA polymerase III with auxiliary protein factors, were found to be remarkably higher in initiation than in elongation of RNA chain. This supports presumptions regarding topological similarities between catalytic centers of bacterial and eukaryotic RNA polymerases. PMID- 1590893 TI - Comparison of estrogen receptor immunocytochemical assay in frozen and paraffin sections. AB - Frozen and paraffin sections of 11 breast carcinomas were stained for estrogen receptors (ER) using the same rat monoclonal primary antibody, D75P3, as the marker and alkaline phosphatase as the chromogen-linking enzyme. The results of this staining process were assessed visually and with the microTICAS image analysis system to determine the degree of correlation between frozen and paraffin-embedded tissue. In all specimens, some fraction of the nuclei stained positively. This included two specimens selected for their biochemically negative assay; one of them stained strongly positively with D75P3. The results of quantitative analysis support the visually apparent correlation between the two types of samples in terms of both overall staining pattern and intensity of nuclear staining. Although the conclusions of this pilot study are limited because of the small number of cases, this method of staining establishes the feasibility of representative ER determination in archival paraffin-processed material. The additional information provided by this method is potentially useful in stratifying patients in prospective studies on the basis of the efficacy of hormonal therapy in biochemically ER positive breast tumors. PMID- 1590894 TI - Multiparameter DNA flow cytometry of keratoacanthoma. AB - Keratoacanthomas (KAs) are rapidly growing cutaneous lesions that frequently look much like well-differentiated squamous cell carcinomas (SCCs) but spontaneously regress. It is uncertain whether KA is a reactive hyperplastic lesion that mimics a neoplasm or a true (but defective) neoplasm that cannot sustain progressive growth. To address this question, we performed DNA flow cytometric analysis on 14 KAs and 10 cutaneous SCCs for comparison. By multiparameter DNA flow cytometry using forward scatter and orthogonal scatter, 10 KAs and 4 SCCs had peridiploid DNA aneuploid populations (DNA indices of 1.03-1.14), and 2 SCCs had grossly aneuploid populations (DNA index, 1.69 and 2.33). Our data thus support aneuploidy in KAs. It is argued that KA is a true neoplasm. PMID- 1590895 TI - Prognostic value of morphometry in acute lymphoblastic leukemia of childhood. AB - The prognostic value of morphometric features was studied in a group of 33 children with acute lymphoblastic leukemia (ALL) and compared with clinical and hematologic parameters. Air dried, May-Grunwald-Giemsa-stained specimens were prepared from iliac crest biopsies, and for each patient, 150 blasts and their nuclei were selected according to a stratified selection method and measured on a graphic tablet system. Univariate overall survival analysis showed the French American-British (FAB) classification to be the strongest clinical parameter (P less than .0001). However, the significance was mainly due to the fact that both L3 cases died; the results for L1 and L2 were less satisfactory, with a survival rate (at 10 years) of 69% for the 26 L1 cases and 80% for the five L2 cases. The nuclear/cytoplasmic (N/C) ratio was the best morphometric feature (P less than .0001) and provided more satisfactory classification results than did FAB: only 2 of the 21 (10%) cases with N/C ratios greater than 0.90 died (7 and 9.5 years after the diagnosis, respectively), and 9 of the 12 (75%) cases with N/C ratios greater than or equal to 0.90 died. For recurrence-free survival analysis, essentially the same results were obtained. The N/C ratio retained its significant prognostic value after recurrence: 11 of the 15 patients with eventual recurrences died; 9 of them had an (original) N/C ratio less than or equal to 0.90. Three of the four recurring cases that survived after recurrence had an N/C ratio greater than 0.90 (P less than .03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590897 TI - Cytometric evidence that cervical intraepithelial neoplasia I and II are dysplasias rather than true neoplasias. An image analysis study of factors involved in the progression of cervical lesions. AB - Image analysis was performed on 40 Feulgen-stained histologic samples and 48 Feulgen-stained cytologic preparations representing normal squamous epithelium and all grades of cervical lesions (from mild dysplasia to invasive carcinoma) in order to characterize the evolutionary progressive changes in cervical epithelial proliferative disease toward malignancy. Quantitative studies included the analysis of proliferative features, differentiation features, nuclear morphology and DNA content. The data obtained on the histologic sections showed that the various features, to a different extent, detected a gradual increase in phenotypic cellular disarrangements related to the progression of the cervical lesions toward malignancy--that is, the modifications to nuclear area, perimeter, DNA content, percentage of nuclei with nucleoli, nuclear/cytoplasmic ratio and percentage of cells with no membrane positivity for soybean agglutinin lectin were progressively greater, moving from normal epithelium and mild dysplasia toward infiltrating carcinoma. In particular, all the morphologic and histochemical features appeared to parallel a diploid reduction and the appearance of aneuploidy. The simultaneous evaluation of proliferation- and differentiation-related features, together with those of nuclear DNA content, showed two main successive preneoplastic lesions: one characterized by an increase in cell turnover without alterations in its organization and another by a true neoplastic disorder. The data obtained on sequential cytologic examinations showed that individual cell changes are detectable and seem basically to be characterized by the appearance of clusters of cells with somatic characteristics not observed in previous cytologic checks. From the results of our study, the cervical intraepithelial neoplasia (CIN) concept appears to be inaccurate. In fact, only CIN III (severe dysplasia/carcinoma in situ) lesions have the morphologic and proliferative alterations of true neoplasia. In contrast, CIN I and some cases of CIN II lesions lack these characteristics and seem to be properly classified as dysplasia, thus avoiding the term neoplasia, implicit in CIN. Moreover, the multivariate study of data sets of features related to the progressive somatic changes, both in histologically and cytologically studied cases, allows us to detect the steps of progression; they are marked by the appearance of cell clusters with qualitatively different phenotypic characters when compared to the cell populations from which they presumably arise. These results seem to provide a further argument against the CIN theory, which stresses the concept that progression is related only to a gradual numerical increase in an initially established phenotype with the characteristics of malignancy. PMID- 1590896 TI - Estrogen and progesterone receptors in breast cancer. Immunohistochemical assay on scraping material. AB - In order to demonstrate the reliability of immunocytochemical results on cytologic specimens for receptor analysis, the expression of estrogen and progesterone receptors was investigated using immunohistochemistry on frozen sections and on scraping material from the same samples of 50 breast carcinomas. The level of agreement between the two procedures was evaluated by the kappa statistic, as was that between each immunohistochemical procedure and the dextran coated-charcoal assay since the latter is still the assay employed most frequently for steroid receptor determination and is used for official reports. Statistical results revealed very good agreement regarding the estrogen receptor analysis, with kappa values of .910 and .952 for the comparison of the dextran coated-charcoal assay with immunocytochemistry on frozen sections and on scrapes, respectively, and .950 for the comparison between the two immunocytochemical procedures. As to progesterone receptors, the kappa values were .795 and .712 for the comparison between the biochemical and immunocytochemical results and .915 for agreement evaluation between the two immunocytochemical procedures. The study showed that the scraping procedure is a valuable tool for the immunocytochemical assessment of steroid receptors in small mammary tumors; it yields representative cellular samples, thus permitting the investigation of heterogeneously distributed substances in tissues. PMID- 1590898 TI - Nucleolar organizer regions in aspirates of malignant lymphomas and benign disorders of the lymph nodes. AB - Silver staining of nucleolar organizer regions (AgNOR) was used to differentiate malignant lymphoma and chronic lymphadenitis. Aspiration smear samples from lymph nodes of 120 cases, including 43 non-Hodgkin's lymphoma, 3 Hodgkin's disease, 56 chronic lymphadenitis, 7 tuberculosis, 6 reactive hyperplasia and 5 samples from other diseases (epidermoid cyst, branchial cyst, mixed tumor, lymphoepithelioma and nodulous disease), were investigated. The number of AgNORs in 200 cells in each sample was counted, and the mean +/- SD in each disease was calculated: non Hodgkin's lymphoma, 6.58 +/- 2.37; Hodgkin's disease, 4.22 +/- 0.5; chronic lymphadenitis, 1.16 +/- 0.1; tuberculosis, 1.13 +/- 0.14; reactive hyperplasia, 1.48 +/- 0.25; other diseases, 1.47 +/- 0.31. The results indicate that the AgNOR count in malignant lymphoma differed highly significantly from that in benign disease (P less than .001). The size of AgNORs in malignant lymphoma and chronic lymphadenitis was measured, and the maximum diameter and area of lymphocyte and lymphoma cell were: lymphocyte, 0.93 +/- 0.12 microns, 0.61 +/- 0.13 microns 2; lymphoma cell, 0.83 +/- 0.22 microns, 0.50 +/- 0.25 microns 2. The AgNOR sizes in malignant lymphoma were significantly smaller than in chronic lymphadenitis (P less than .001). PMID- 1590899 TI - Photographic densitometry for quantitative DNA analysis of cytologic and histologic specimens. AB - We found that photographic densitometry (PD) is a useful technique for quantitative determinations of nuclear DNA content in clinical tumor material. Optimum conditions for the use of PD in clinical cytology and histopathology were worked out. A quantitative evaluation of the method was performed, particularly with respect to errors that may appear when measuring clinical tumor material. Our study showed that PD offers accurate DNA measurements in cytologic and histologic specimens. Ploidy level determinations in tumor cell populations in clinical material could be as accurately performed with PD as with scanning microspectrophotometry (SMP). Nuclear DNA content of individual cells as determined by PD correlated highly with nuclear DNA content determined by SMP (correlation coefficient, 0.96). Since the PD method is less influenced by background variation than are other image techniques (due to measurement of a photographic image), it is particularly useful in measurement of histopathologic sections, in which the background variation can introduce considerable errors. The method is also valuable with clinical cytologic smears, in which the presence of blood and other material disturbs the background. PD represents a valid complement to scanning microspectrophotometry and TV imaging systems, particularly for DNA analysis of tissue sections. Moreover, it can be applied easily in the clinical routine. Relevant tissue areas are selected and photographed by the pathologist or cytopathologist, and the measurement is performed by a laboratory technician. PMID- 1590900 TI - Quantitative peroxidase-antiperoxidase complex-substrate mass determination in tissue sections by a dual wavelength method. AB - The aim of this study was to develop a method of quantitating prostate-specific acid phosphatase (PSAP) in histologic sections of prostate tumor tissue labeled with the peroxidase-antiperoxidase (PAP) complex technique using diaminobenzidine (DAB) as a substrate. Studies of PAP-DAB- and hematoxylin-stained prostate tissue sections were performed with a black-and-white, computerized microscope image system. The mass of brown reaction product generated in PAP-DAB staining was the indicator of PSAP intensity. The mass of brown reaction product was determined by using a dual wavelength method in which two 10-nm bandpass filters, peaked at 450 and 510 nm in wavelength, were used. The wavelength-dependent ratio of mass absorptivity of PAP-DAB stain (brown product) and that of hematoxylin (blue product) were estimated at wavelengths of 450 and 510 nm by using slides stained with only PAP-DAB or hematoxylin. The accuracy of the mass measurements, investigated by relating the measurement to the true mass of the brown PAP-DAB product, is reported. There was no significant difference between the measurements at magnifications of 10x, 20x, 40x or 60x in the reproducibility investigation. The PSAP stain intensity was quantitatively determined by the difference of the PAP-DAB stain mass per pixel between the tumor and normal cell region. The relationship between the objective measurement and the conventional subjective grades is presented. PMID- 1590901 TI - DNA ploidy and cell cycle analysis in ear malignant melanoma by flow and image cytometry. AB - Sixteen ear malignant melanomas (MM) were studied for ploidy and cell cycle analysis by flow and image cytometry. The results were compared with clinical (age, sex, stage), histologic (depth of invasion, level, type) and prognostic (recurrence, death) parameters. Single nuclear suspensions were obtained from fixed, paraffin-embedded tumor and adjacent normal tissue processed separately according to Hedley's technique. These, a "spiked" specimen of normal tissue and tumor, and a spleen diploid control were analyzed on a FACScan flow cytometer (Becton Dickinson, Mountain View, California, U.S.A.). Feulgen-stained Cytocentrifuge preparations of nuclear suspensions of normal, MM and diploid spleen were analyzed with the CAS 200 Image Analyzer (Cell Analysis Systems, Inc., Elmhurst, Illinois, U.S.A.) against commercial calibration rat hepatocytes defined as diploid. Six (37.5%) MM were diploid, and 10 (62.5%) were aneuploid; 8 (90%) were hypodiploid, for a high frequency. There were no statistically significant correlations between clinical, pathologic, prognostic or cell cycle analysis parameters and ploidy, although poor prognostic features tended to be in aneuploid lesions. PMID- 1590902 TI - DNA content in fresh versus paraffin-embedded tissue. Flow cytometric analysis of 100 tumors. AB - DNA ploidy analysis was determined on 100 consecutive tumors from a wide variety of sites using both fresh and paraffin-embedded tissue on the same specimen. The correlation coefficient (r) value between the methods was 0.85. Aneuploidy was detected by both methods in 51/100 (51%) of the cases. Fresh tissue analysis yielded 10 additional cases (overall 61% aneuploidy) not detected on corresponding paraffin-embedded sections, whereas paraffin-embedded analysis detected 4 additional cases (overall 55% aneuploidy) not revealed by fresh tissue analysis. Fresh tissue analysis produced lower coefficients of variation and resulted in a cleaner preparation with less cellular debris. Fresh tissue analysis was also superior to paraffin for the detection of hypodiploid, near diploid and multiple peaks. Analysis of paraffin-embedded material allows examination of archival tissue and provides a more rapid means of long-term follow-up and statistical correlations for prognostic studies. Although the overall correlation of both methodologies for DNA analysis showed a minimal variation in results, in our experience fresh tissue analysis has an advantage and is preferable, when available, for ploidy analysis. PMID- 1590903 TI - Comparison of the chromatin stainability of human spermatozoa separated by discontinuous Percoll gradient centrifugation. A flow cytometric contribution. AB - Many clinical programs in in vitro fertilization (IVF) use the classic Percoll sperm preparation technique to obtain a subpopulation of highly mobile spermatozoa. This Percoll discontinuous gradient centrifugation technique (densities ranging from 1.042 to 1.116 g/mL) was used at room temperature to separate human spermatozoa fractions in order to determine differences in chromatin stainability. The stainability was measured by analysis of DNA fluorochrome uptake by flow cytometry using human peripheral blood lymphocytes as an internal standard. A significant difference in chromatin stainability was noted between the residual fraction (immobile spermatozoa remaining at the top of the Percoll gradient) (44.2%) and the selected one (highly mobile spermatozoa harvested in the 90% and 100% steps) (36.3%). The sperm DNA heterogeneity, as defined by the coefficient of variation (CV), was significantly lower for the selected fraction as compared to the residual one (CV = 12.8% versus 15.4%). A marginal population of spermatozoa adjacent to the germinal peak was also identified. The percentage of this marginal population was significantly lower for the selected fraction as compared to the residual one (7.4% versus 22%). Using a biochemical in vitro decondensation method, the chromatin stainability of the selected and residual fractions (56.9% versus 62.9%) was also determined, demonstrating that the chromatin of the selected fraction was less stainable. This study confirmed that Percoll centrifugation selects a germinal population that is denser and less stainable than with other techniques and analyzed the relation between density, high mobility and probable capacitation. PMID- 1590904 TI - General considerations and complications of the ileostomy. PMID- 1590905 TI - Natural evacuation versus irrigation. AB - The comparison of the influences of the natural evacuation method and the colostomy irrigation method on complaints, daily activities and psychosocial conditions revealed that colostomy irrigation, as compared to natural evacuation, imposes less distress on the patient, causes fewer skin problems and is less of a financial burden. In daily activities, irrigation causes fewer difficulties in comparison to natural evacuation in the areas of bathing and sleeping. Furthermore, the frequency of going outdoors remains at the same level as in pre operative days and the patients are able to adjust to daily activities post operatively. By comparing irrigation patients and natural evacuation patients from a psychosocial standpoint, irrigation patients hold a higher degree of self esteem, have fewer anxieties and fewer worries than those using natural evacuation. The instruction of evacuation control, management of gas odor, and a great deal of psychosocial support needs to be given to natural evacuation patients. PMID- 1590907 TI - Patient education sheets. PMID- 1590908 TI - Convexity in the management of problem stomas. PMID- 1590906 TI - Novel wound care yields positive results. PMID- 1590909 TI - AHCPR update. The guidelines for urinary incontinence in adults. PMID- 1590910 TI - Psychiatric diagnosis and uncooperative behavior in nursing homes. AB - The prevalence of psychiatric disorders and behavioral disturbances in nursing homes is high, but the relationship between the two is unknown. We studied 454 new admissions who were diagnosed by research psychiatrists using DSM-III-R criteria and compared patients who nursing staff designated as cooperative or uncooperative by psychiatric diagnosis and use of restraints and neuroleptics. Uncooperative patients (n = 79; 17.4%) had a variety of psychiatric disorders (total, 87.3%) but particularly had dementia syndromes complicated by delusions, depression, or delirium (44.3%). Uncooperative patients were more frequently restrained and prescribed neuroleptics. Determining the origins of behavior disorders in patients with psychiatric disorders in nursing homes may reduce behavior disturbances. PMID- 1590911 TI - Clinical heterogeneity of probable Alzheimer's disease. AB - When the symptomatology in probable Alzheimer's disease (AD) was studied, two subgroups emerged: one with predominant cortical symptoms of parietal type (AD type I) and another with general cognitive symptoms but absence of or only mild cortical symptoms (AD type II). In AD type I, the age at onset was significantly lower, confusional symptoms and leukoariosis on computerized tomographic scan were less frequent, and the ganglioside GM1 concentration in cerebrospinal fluid was significantly higher than in AD type II. Although the significance of changes in cerebrospinal fluid gangliosides has not been fully elucidated, it is possible that the increase in cerebrospinal fluid GM1 reflects a more severe degeneration of neurons and synapses in AD type I than in AD type II. The relation between symptomatology and leukoariosis suggests that leukoariosis has clinical significance in AD patients. The total results suggest heterogeneity of probable AD. AD type I appears to constitute a classic AD subgroup with memory disturbances and marked cortical symptoms of parietal type, while age-related changes, vascular changes, and leukoariosis may be responsible for the more generalized symptomatology in AD type II. PMID- 1590912 TI - 1-Methyl-4-phenylpyridinium (MPP+) but not 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) serves as methyl donor for dopamine: a possible mechanism of action. AB - 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4 phenylpyridinium (MPP+), the active product of MPTP, caused Parkinson's disease like symptoms. The mechanism of action of MPP+ is unknown, but analogues of MPTP lacking an N-methyl group were found to be essentially devoid of toxicity, which means that the methyl group of the pyridine ring plays a role in the toxicity. This is of interest because S-adenosylmethionine (SAM), which is the biologic methyl donor and requires a methyl group for its action, also caused MPP(+)-like motor deficits in rodents. Therefore, the requirement of a methyl group by MPTP and MPP+ for their actions suggests that, like SAM, MPP+ and MPTP may serve as methyl donors. This hypothesis was tested by reacting SAM, MPP+, or MPTP with dopamine in the presence of catechol-O-methyltransferase and measuring the methylated product of dopamine produced. Like SAM, MPP+, but not MPTP, methylated dopamine. The methylated product coeluted from chromatographic columns with standard 3-methoxytyramine. Concentrations of 15.6, 62.5, 250, and 1000 nmoles/tube increased the 3-methoxytyramine recovered above controls by 0.0, 6.88, 44.55, 129.47 and 5.8, 13.9, 50.58, 121.31 nmoles for SAM and MPP+, respectively. The dopamine that remained unreacted was dose-dependently decreased. MPTP had no significant effect. The ability of MPP+ to serve as a methyl donor may represent a mechanism for the toxicity of MPP+. PMID- 1590913 TI - Entrained body temperature rhythms are similar in mild Alzheimer's disease, geriatric onset depression, and normal aging. AB - Sleep-wake rhythms are known to be altered in Alzheimer's disease (AD) and in unipolar depression. Other evidence suggests that the circadian rhythm in body temperature may be altered as well. Entrained circadian temperature rhythms were measured in healthy elderly men and women, as well as in men and women suffering from unipolar depression or mild AD, to examine this possibility. There were no differences in the temperature rhythm characteristics of subjects with depression or AD compared with healthy control subjects. However, gender differences were observed. Female control subjects showed a larger amplitude, higher peak temperature, and earlier acrophase relative to male control subjects. Also, the mesor of female AD subjects was higher than for male AD subjects. These results are discussed in the context of the widely varying subject populations used in other studies. PMID- 1590914 TI - Investigation of gait in elderly subjects over 88 years of age. AB - To evaluate senile gait patterns in octagenarians and nonagenarians, we provided a standardized questionnaire on gait disabilities to 153 elderly subjects over 88 years of age. Subjects represented a relatively healthy subgroup of noninstitutionalized residents who participated in a gerontological survey of all inhabitants of the city of Leiden who were 85 years of age or older. Of the 142 subjects who responded to this questionnaire, 87 persons (61%) claimed distinct diseases as a cause of gait impairment. Forty-two of the remaining 55 persons were investigated neurologically and received a standardized assessment of gait. Twenty-five persons (18% of all responders) had a completely normal gait, whereas a wide spectrum of gait abnormalities--mainly with ataxic features--was encountered in the remaining persons. It is concluded that a surprisingly high number of very old community residents can have a completely normal gait. Gait disorders in this age group are most frequently associated with common distinct diseases. In addition, many elderly have a gait disturbance of variable clinical nature and unclear pathologic basis, which may represent the "idiopathic senile gait." PMID- 1590915 TI - Motor cortex involvement in presenile dementia: report of a case. AB - Alzheimer's disease (AD) is characterized neuropathologically by high densities of neurofibrillary tangles (NFT) and neuritic plaques (NP) in the cerebral cortex, in particular in neocortical association areas and in the hippocampal formation. We report here the case of an AD patient who developed signs of motor dysfunction early in the clinical evolution. A quantitative neuropathologic analysis revealed much higher densities of NFT and NP in the primary motor cortex than is usually observed in AD. This case, together with other reports, points to the existence of neurologically defined subgroups of AD with unusual clinical deficits that are correlated with the regional and laminar distribution of NP and NFT, and further supports the hypothesis that the symptomatology presented by AD patients results from the loss of specific neuronal populations leading to a syndrome of global cortical disconnection. PMID- 1590916 TI - Expression of a partial synthetic human TNF cDNA in E. coli. AB - A recombinant human tumour necrosis factor (rhTNF) cDNA was constructed. The TNF gene was isolated from a human genomic gene library. There are four exons in the TNF gene. The fourth exon codes for 140 amino acids of the TNF matured protein which is composed of 157 amino acids. A major portion of the fourth exon was isolated and then ligated to a synthesized DNA fragment coding for the remaining amino acids. The partial synthetic hTNF (rhTNF) cDNA thus generated was subcloned into a vector and successfully expressed in E. coli. 5-1 fermentator was used to produce rhTNF. About 20 g (wet weight) of bacterial pellet per liter medium and 10(6)-10(7) units of cytotoxicity to L929 cells per milliliter medium were obtained. rhTNF was purified by HPLC and dried with a freeze dryer. rhTNF with a purity of about 95% in the form of white powder was obtained. The sequence of ten amino acids at the amino terminus of the rhTNF was determined. The result showed that it was identical with that of the natural human TNF. PMID- 1590917 TI - The characteristics and motion model of insulin monomer. AB - The extensive conformational comparisons among the determined structures of the different species and crystal forms of insulin and the varied insulin derivatives were performed by using the least-squares superimposition technique and the graphics technique. The results of the investigation showed that the structure of molecule I in 2Zn insulin was closer to that of the natural monomer; the conformational difference between two molecules of a dimer came out during dimerization and it was further improved and stabilized during the hexamerization and packing of hexamers in crystal; through the hinge peptides, such as A10, B4, B8, B24, B20 and B23, there was a flexible relative motion among the structural segments in the insulin molecule, and the residues at the B-chain C-terminal might have a shift of more than 10A; the mobility for each residue side-chain was very different due to the different surroundings. PMID- 1590918 TI - Role of thiol-disulfide exchange in insulin binding to its receptor. AB - The effects of reduction by DTT, oxidation by DTNB and treatment with NEM on the thiol contents and insulin binding to its receptor in mice liver membranes were studied. Reduction with DTT leads to a parallel increase in the thiol content and the specific binding of insulin to the membrane. Scatchard analysis of the results shows little change in the number of binding sites but a twofold increase of the binding constant. Washing the membrane with bound insulin by a DTT containing buffer results in a more marked increase in the release of bound insulin than washing with buffer alone, suggesting that part of the insulin is bound to its receptor by covalent disulfide linkages through a thiol-disulfide exchange reaction and reduction with DTT leads to a marked increase in this "disulfide-linked" insulin. Treatment with DTNB or NEM of the DTT-reduced membrane seems to reverse the effect of DTT reduction, although the reaction of the untreated membrane with DTNB or NEM had little or no effect on the specific binding of insulin. It is suggested that initially, part of the thiols responsible for the exchange reaction may not be available for reaction with DTNB and reduction with DTT generates further thiols leading to increased specific binding in general and increased insulin binding to the receptor through covalent disulfide linkages in particular. PMID- 1590919 TI - A strategy for isolating differentiation-inducing complementary DNAs from human esophageal cancer cell line treated with retinoic acid. AB - Treatment of the human esophageal cancer cell line EC8712 with retinoic acid (RA) stopped the cell growth significantly and gave rise to terminal differentiation of the cells characterized by increased expression of involucrin gene. Two cDNA libraries were constructed from the parental and RA-treated cells respectively. Repeated subtractive hybridization of single-stranded plasmid DNA prepared from pooled colonies of cDNA library of the parental cells with cDNA probe generated from the RA-treated cells exhausted sequences common to both libraries of the cell. The unhybridized cDNA probe represented, therefore, the genes activated after RA-treatment. By using these enriched cDNAs as probe to screen the cDNA library constructed from the RA-treated cells thirty-nine positive colonies were obtained, of which two were specifically due to RA-induction. One of these two cDNA clones, designated as pRA538, has undergone further analysis and shown differentiation-inducing effect on parental cancer cells. A novel strategy for cloning genes involved in terminal differentiation of cancer cells is developed. PMID- 1590920 TI - An HBV large surface antigen protein which can be secreted from mammalian cells. AB - The N-terminal 54 base pairs (encoding amino acid residues 2-19) within the preS1 region of the human hepatitis B virus surface antigen gene were deleted by site directed mutagenesis. Unlike the wild type large surface antigen protein, when this mutated gene was expressed in monkey kidney cell line COS-M6, the protein product (S301 protein) could be secreted from the cells. Moreover, the inhibition of the secretion of the major surface antigen protein by this altered large surface antigen protein was greatly reduced, suggesting that the deleted region contained a retention sequence which prevented the secretion of the large surface antigen. However, the coexpression of the major S protein was essential for the secretion of the S301 protein. When coexpressed, the secretion of these two proteins was synchronous. Like the wild type large surface antigen protein, the S301 protein could be translocated into endoplasmic reticulum and glycosylated after its synthesis in COS cells. The S301 protein was thermostable and proteinase-resistant. It also retained the antigenicity of the large S and major S proteins. Given the fact that the S301 protein is readily secretable, stable and identical to the large S protein in terms of their antigenicity, it may be developed into a new generation of recombinant vaccine for the prevention of viral hepatitis. PMID- 1590921 TI - Sun tanning-related burns--a 3-year experience. AB - A retrospective study has analyzed 562 sun-related burns out of 19,643 patients treated at our institution from 1 March 1988 to 28 February 1991. These patients were analysed according to sex, age, burn area, mode and length of treatment and outcome. Females, mainly adults, represented 60.8 per cent of all patients presenting burned due to sun bathing. There is a marked seasonal incidence, proportionally constant throughout these 3 years. The main causes of injury were sun only (36.7 per cent), sun plus fig leaf 'tea' tanning lotion (17.7 per cent) and lemon juice (17.7 per cent). Healing to normal skin appearance was achieved in 99.1 per cent, 0.7 per cent healed with scarring and one patient died due to massive sepsis. The effect of sunlight on skin and the process of 'sunburn' when using homemade plant-derived tanning lotions containing substances which can induce a photodermatitis reaction is also discussed. PMID- 1590922 TI - Effect of acute and chronic lipopolysaccharide (LPS) administration on reticuloendothelial system (RES) phagocytic activity in vivo. AB - The effect of injection or chronic infusion of lipopolysaccharide (LPS) into unanaesthetized rats on the distribution of [99Tcm-]SC has been determined. At a dose of 2.5 mg/kg, LPS injection caused a marked alteration in the distribution of the radiolabelled material, with more uptake being achieved in the lung while less was taken up by the spleen. Kidney and liver uptake were also changed. Chronic infusion of LPS at a similar dose (3 mg/kg in 24 h) caused a marked increase in the uptake of the radioactive material by the lung only. These data are consistent with a working hypothesis that the alterations in RES phagocytic activity of the lung observed in rats subjected to burn trauma could be related in part to LPS, either coming as a bolus, or being continuously presented. PMID- 1590923 TI - Comparison of prognostic indices for burns and assessment of their accuracy. AB - Logistic regression was used to create four individual models of prognostic indices based on our patient population. The simplest index using only three factors, age, extent of full skin thickness burn and inhalation injury, proved to be best. These models were also compared with established indices, like Baux's, Bull's and Roi's. For a specificity below 80 per cent, Baux's rule fits as well as Roi's index does. Changes in treatment modalities and improvement in therapy will influence the accuracy of an index. Indices must be adapted to changing conditions to avoid increasing false prediction of death. PMID- 1590924 TI - Neopterin as parameter of cell-mediated immunity response in thermally injured patients. AB - Serum neopterin levels have been determined retrospectively in 22 patients with burn injuries. Neopterin, which is produced by monocytes/macrophages following stimulation by interferons, is regarded as a marker for the activation of the cellular immune response. In most patients neopterin levels were initially in the normal range. All patients had their first operation and skin transplantation during the first week; mean neopterin levels increased significantly thereafter. Further skin transplantations or infections did not significantly influence the elevated neopterin level. This result may be due to continuous stimulation of the cellular immune system, as indicated by the elevated neopterin levels during most of the follow-up. In four low risk patients, neopterin levels always remained in the normal range. Two patients with inhalation trauma showed highly elevated neopterin levels (30-70 nmol/l) already upon admission and for 3 days thereafter. No correlation of neopterin levels with the burned body surface area was observed. However, mean serum neopterin levels were higher in the group of non survivors (five patients) compared to survivors during the first 2 weeks after the trauma; rising neopterin levels were observed during the last 5 days before death. Although elevated neopterin levels could not be attributed either to the burn itself or to later events, the cellular immune system of burned patients was shown to be highly activated. PMID- 1590925 TI - Increased transcellular permeability of rat small intestine after thermal injury. AB - The pathway which results in a loss of intestinal barrier function and transepithelial transfer of macromolecules after cutaneous thermal injury is unknown. To determine the enhanced absorption pathway, transepithelial transport of horseradish peroxidase (HRP) was examined ultrastructurally after a thermal injury. Within 6 h after the injury, increased HRP uptake was seen in the portal and systemic blood with the maximal increase in uptake measured at 18 h postinjury; permeability returned to normal by 72 h postinjury. Morphologically, the increased uptake was found to be transcellular through ultrastructurally normal intestinal absorptive cells. Occasional focal regions of enhanced HRP uptake were found and this enhanced uptake was attributed to focal intestinal epithelial disruptions. This increase in intestinal permeability represents a transient loss of intestinal barrier function and potentially allows absorption of macromolecules such as endotoxin from the intestinal lumen into the portal circulation early after thermal injury. PMID- 1590926 TI - Long-term psychosocial adjustment in patients with severe burn injuries: a follow up study. AB - An investigation of the long-term psychosocial adjustment of patients with severe burn injuries is presented. In the selected 13-year period (1968-80) 46 patients fulfilled the entry criteria: burns covering more than 30 per cent body surface area (deep dermal or full skin thickness). Seventeen patients died early and one later. Of the remaining 28 patients, contact was made with 25 (89.3 per cent) who all participated. The observation time ranged between 7 and 21 years. The patients received a semi-standardized interview adjusted for age at the time of burn injury, a psychiatric interview and a physical examination to assess the permanent character and functional loss. The principal findings were: no correlation could be found between degree of disfiguration/function loss and the long-term psychosocial adaptation after severe burn injuries. The determinant factor was the premorbid psychiatric/psychological integration and, to some extent, support from staff and relatives. PMID- 1590927 TI - High-dose vitamin C therapy for extensive deep dermal burns. AB - We studied the haemodynamic effects of antioxidant therapy with high-dose vitamin C administration (170 mg/kg/24 h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with vitamin C; and group 3 with 25 per cent of the Parkland formula without vitamin C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of vitamin C. With adjuvant high-dose vitamin C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output. PMID- 1590928 TI - The roles of macrophage (M phi) and PGE-2 in postburn immunosuppression. AB - Postburn immunosuppression in mice with full skin thickness burns was assessed after Con A stimulation of splenic lymphocytes. The immunosuppression was detected within 24 h of injury and was maximal 3-7 days later. Such lymphocyte proliferation was enhanced by depletion of adherent cells (M phi) in burned mice and could be depressed in normal mice by injection of these adherent cells from burned mice. These results suggest the presence of M phi s with a suppressor function. No difference in spontaneous blastogenic transformation (SBT) of spleen cells between the burned and normal mice was found, but after removal of the M phi s the SBT of spleen cells of burned mice became significantly elevated. Hence both M phi and lymphocytes in mouse spleen cells were activated after severe thermal injury. PMID- 1590929 TI - Burn care facilities in Italy. PMID- 1590930 TI - An analysis of resuscitative requirements of petrol (gasoline) burns. AB - A retrospective study was carried out to confirm the clinical impression that petrol (gasoline) burns had a greater resuscitation requirement than other types of thermal injury. A total of 450 admissions to the St Andrews Hospital Regional Burn Unit from 1982 to 1988 were reviewed. Patients with pre-existing cardiovascular disease, respiratory disease, inhalation injury and fatalities occurring within the first 72 h of admission were excluded from the study. Forty four patients met all requirements for inclusion within the study. These 44 patients consisted of 15 with petrol burns and 29 with non-petrol burns, all of whom were resuscitated using the modified Muir and Barclay formula, with adjustments made on the basis of clinical and laboratory monitoring. Comparison of resuscitation requirements of the two groups by the Wilcoxon Rank Sum Test showed that the petrol burns group had a significantly greater fluid resuscitation requirement (P less than 0.01). PMID- 1590931 TI - Comparison of calcium sodium alginate (KALTOSTAT) and porcine xenograft (E-Z DERM) in the healing of split-thickness skin graft donor sites. AB - In a controlled, prospective study, calcium sodium alginate and porcine xenograft were compared in the treatment of split-thickness skin graft donor sites on 20 patients. Half of each donor site was dressed with each material. Time to complete healing, quality of regenerated skin and patient comfort were assessed. Time to healing was 8.1 days with alginate and 11.3 days with porcine xenograft (P less than 0.001). Quality of healed skin was consistently good with the alginate, and better than under the xenograft in 95 per cent of patients (P less than 0.001). Hypertrophic scarring was not observed under alginate dressings but occurred in 25 per cent of xenograft-dressed sites (P less than 0.01). In addition, evidence was found that allergic reactions to porcine xenograft could occur. Alginate was preferred by 75 per cent of patients and none preferred porcine xenograft (P less than 0.01); the remainder had no preference. It was concluded that porcine xenograft is inferior to calcium sodium alginate as a dressing for split-thickness skin donor sites. PMID- 1590932 TI - Burns in patients over 60 years old: epidemiology and mortality. AB - Epidemiology and mortality among burn patients over age 60 years who were admitted to the Burn Centre of La Fe Hospital (Valencia, Spain) between 1 January 1988 and 1 January 1991 have been studied. A total of 443 patients (7.8 per cent of all presenting patients) were hospitalized during this 3-year period; of these, 69 (15.5 per cent) were over 60 years old. There were 40 females and 29 males (mean age, 72.2 years). Mean burn area was 21.6 per cent of total body surface, and the most commonly involved regions were the lower limbs (81 per cent). Fire flames were the most common cause of burns (65.2 per cent) and produced the most extensive lesions. Eight-five per cent of the accidents occurred at home, and winter was the season of highest incidence. Patient mortality was 33.3 per cent, the most common causes of which were hypovolaemic shock during the first 24 h and pneumonia in the later stages. PMID- 1590933 TI - Reduction of the mortality rate in aged burn patients. AB - The management of elderly burn patients is time consuming for both nursing staff and physicians, and therapy remains often challenging and controversial. In a retrospective study, we analysed the outcome of two periods with different treatment modalities. An increased number of nurses, a change in the local burn wound treatment, better documentation of wound status and general conditions, and last, but not least, of nutritional aid, enabled us to reduce the mortality rate in patients over 65 years of age. PMID- 1590934 TI - New economical skin graft expansion wheel. AB - A simple and economical mesh graft expansion wheel is described. The instrument does not need any consumables--carriers for example--and is very low priced compared with other expanders. A small institution or a private practising surgeon in this country can afford it. It is possible to increase or reduce the number of wheels to individual surgeon's requirements. Different expansion ratios can be obtained by simple changes in design. PMID- 1590935 TI - Gunpowder-related burns. AB - Gunpowder misuse is a frequent cause of burn injury in our area. The injuries are mostly minor lesions which may be treated on an outpatient basis, the more serious injuries need surgical treatment. Experience of the management of these burns is reported by reviewing 123 clinical charts of patients admitted between 1983 and 1990. The most frequent victims are teenage males who are involved mainly in accidents in the street. The most serious burns followed work-related accidents, with a fatal outcome in 47 per cent of the patients. The serious burns are usually deep dermal or full skin thickness. A common pattern affects groins, genitalia, hypogastrium and hands, and are produced when fireworks ignite in the pockets of the patient's trousers. The management of these lesions does not differ from burns caused by other agents, although attention should be paid to the presence of associated lesions, chiefly to eyes, ears and hands, due to the shockwave and shrapnel. PMID- 1590936 TI - Chemical burn with cresol intoxication and multiple organ failure. AB - In general, immediate water irrigation is recommended for all chemical burns. Very few chemicals cannot be safely washed off the skin with water, however cresol is one of the exceptions. A 40 per cent TBSA cresol chemical burn that subsequently developed systemic intoxication and multiple organ failure is reported. The patient survived after intensive general supportive treatment, repeated haemodialysis and wound care. PMID- 1590937 TI - Massive haemorrhage due to rectosigmoid ulcers in a patient with extensive burns. AB - A 36-year-old white-skinned male was admitted with 45.5 per cent burns, mostly of full skin thickness. Severe rectal bleeding from rectal ulcerations developed on postburn day 12. Various conservative attempts at management failed, and after multiple transfusions, abdominoperineal resection was carried out with eventual complete recovery. Complications during his acute phase included Pseud. aeruginosa sepsis and Clostridium difficile diarrhoea. Extensive skin grafts were required. The cause of the rectal ulcerations is unclear. PMID- 1590938 TI - Rupture of the quadriceps mechanism as a late complication of burn injury. AB - Full skin thickness burns around the knee often leave the patellar tendon and bone exposed. An example of the late rupture of the quadriceps mechanism following such a burn and subsequent reconstruction is described. Rupture of the quadriceps mechanism as a complication of burn injury has not previously been described. PMID- 1590939 TI - Metabolic and immune effects of enteral ascorbic acid after burn trauma. AB - A burned guinea-pig model (30 per cent BSA) was used to study the effect of vitamin C on immune and metabolic responses following burn trauma. Thirty-six guinea-pigs received identical enteral diets (175 kcal/kg) except for the amount of vitamin C. Groups I, II, III and IV were given formulae delivering no vitamin C, (1 RDA) 15 mg/kg/day, 75 mg/kg/day or 375 mg/kg/day, respectively. Resistance to infection was evaluated by injecting each animal with 0.1 ml of 1 x 10(9) Staph. aureus 502A subcutaneously on day 10. On day 14, Staph. aureus abscesses were excised and the numbers of viable colonies were determined. Results showed no statistical differences between groups in the clearance of Staph. aureus. From days 2 to 12, animals in groups I, II and III had body weights of approximately 97 per cent of preburn body weight. Animals in group IV, however, had a body weight gain, 102 per cent of preburn body weight on day 12. Animals in group IV also had significantly lower metabolic rates on day 12 as compared to the animals in the other groups. These results suggest that large amounts of vitamin C have beneficial effects on the maintenance of body weight and metabolic rate following burn trauma. PMID- 1590940 TI - Selective intestinal decontamination for prevention of wound colonization in severely burned patients: a retrospective analysis. AB - In this study the effect of selective intestinal decontamination of the digestive tract (SDD) on wound colonization was investigated. Ninety-one patients with at least 25 per cent total burned surface area (TBSA) were included in this study. All patients received oral polymyxin. In 63 patients oral co-trimoxazole and amphotericin B were added to the regimen. The addition of co-trimoxazole decreased the incidence of Enterobacteriaceae wound colonization from 71 per cent to 11 per cent (P less than 0.005). Colonization with Proteus was eliminated in patients treated with co-trimoxazole, compared with an incidence of 36 per cent in the group treated with polymyxin alone (P less than 0.001). The addition of amphotericin B decreased yeast colonization of the burn wound from 39 per cent to 10 per cent (P less than 0.005). A close relation was observed between burn wound colonization and colonization of the gastrointestinal tract. No resistant bacterial strains emerged during the period of study. These results suggest that SDD is an effective method for prevention of wound colonization. Further controlled studies are needed to establish the role of SDD in preventing burn wound colonization and wound sepsis. PMID- 1590941 TI - Hematopoietic transcription regulators and the origins of leukemia. PMID- 1590942 TI - The uses of intravenous immunoglobulin in pediatrics. An update. PMID- 1590943 TI - Interactions between oestradiol and the progesterone antagonist RU-486 in establishing and maintaining female rats' sexual responsiveness: central versus peripheral effects. AB - Progesterone is well known to contribute specifically to the emergence of the female rats' sexual behaviour by the establishment of 'proceptivity'. Analysis of the mechanism of progesterone action benefits from the availability of highly effective anti-progestagenic compounds. However, results obtained during the study of female rats' sexual behaviour, including such compounds into the experimental protocol, appear equivocal. The present experiments were designed to further examine the possible effects of the antiprogestagenic compound RU-486 (Mifepristone) on the female rats' sexual responsiveness as elicited through exposure of the animals to oestradiol alone. The experimental design aimed to distinguish between receptivity (defined as response to sexually active males) and proceptivity (defined as female-initiated sexual behaviour). Mifepristone advanced the onset of receptivity after the injection of oestradiol benzoate (OB). Upon further investigation a steady level of receptivity was reached during prolonged treatment with OB and this level appeared unaltered through concurrent treatment with Mifepristone. OB alone was insufficient to induce full proceptivity as revealed by observations of sexual behaviour with tethered males. Such defined proceptivity was significantly further inhibited by Mifepristone. It thus appears that, dependent upon the time and type of female sexual behavioural analysis, Mifepristone either enhances, inhibits, or does not affect sexual responsiveness. After the observation period, autopsy revealed the presence of copulatory plugs and infections in the uterus of OB + Mifepristone-treated rats. This unexpected finding could result from effects of the compound on the uterine cervical musculature. Uterine infections might result in painful, aversive, intra abdominal sensations, especially during intravaginal penile intromissions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1590944 TI - Exploratory activity and response to a spatial change in rats with hippocampal or posterior parietal cortical lesions. AB - Rats with bilateral lesions of posterior parietal cortex (PPC: Krieg's Area 7) or dorsal hippocampus (HIP) were compared with controls for their response to environmental change. In the first experiment, following subjects' exploration of a relatively homogeneous open-field environment, a stimulus-rat was introduced at a particular location beneath the glass floor. All groups selectively explored the location of the stimulus-rat, but only the control and PPC groups displayed habituation. On removal of the stimulus-rat, only the control group selectively re-explored the place where the stimulus-rat had been. A second experiment, similar to the first, used additional prominent visual cues beneath the floor. When the cues were spatially separate from the location of the stimulus-rat (Dissociated object condition), the same results were obtained as in the first experiment. When the additional cues were positioned close to the stimulus-rat location (Associated object condition), habituation occurred in all groups including the hippocampal group, and again the removal of the stimulus-rat resulted in a selective re-exploration of its former location in the control group only. However, a selective preference for staying at the stimulus-rat's previous location was found in PPC animals as in controls. Hippocampal rats failed to investigate the location of the missing stimulus in all conditions. The results confirm the role played by the hippocampus in spatial memory and suggest that the posterior parietal cortex is involved in the cognitive-demanding aspects of spatial encoding, particularly in environments that are poorly visually differentiated. PMID- 1590945 TI - Dissociation of spatial navigation and visual guidance performance in Purkinje cell degeneration (pcd) mutant mice. AB - Spatial learning in rodents requires normal functioning of hippocampal and cortical structures. Recent data suggest that the cerebellum may also be essential. Neurological mutant mice with dysgenesis of the cerebellum provide useful models to examine the effects of abnormal cerebellar function. Mice with one such mutation, Purkinje cell degeneration (pcd), in which Purkinje cells degenerate between the third and fourth postnatal weeks, were evaluated for performance of spatial navigation learning and visual guidance learning in the Morris maze swim-escape task. Unaffected littermates and C57BL/6J mice served as controls. Separate groups of pcd and control mice were tested at 30, 50 and 110 days of age. At all ages, pcd mice had severe deficits in distal-cue (spatial) navigation, failing to decrease path lengths over training and failing to express appropriate spatial biases on probe trials. On the proximal-cue (visual guidance) task, whenever performance differences between groups did occur, they were limited to the initial trials. The ability of the pcd mice to perform the proximal-cue but not the distal-cue task indicates that the massive spatial navigation deficit was not due simply to motor dysfunction. Histological evaluations confirmed that the pcd mutation resulted in Purkinje cell loss without significant depletion of cells in the hippocampal formation. These data provide further evidence that the cerebellum is vital for the expression of behavior directed by spatial cognitive processes. PMID- 1590946 TI - The limbic system and food-anticipatory circadian rhythms in the rat: ablation and dopamine blocking studies. AB - Rats behaviorally anticipate a fixed, daily opportunity to feed by entrainment of circadian oscillators that are physically separate from the light-entrainable circadian pacemaker that has been localized to the suprachiasmatic nucleus. Neural substrates mediating food-entrained rhythms are unknown. A variety of anatomical and functional observations suggest possible involvement of the limbic system and its dopaminergic component in the regulation of these rhythms. To test this hypothesis, the activity rhythms of rats bearing large, combined ablations of the hippocampus and amygdala or nucleus accumbens and medical forebrain anterior to the thalamus were examined under ad-lib feeding, 2 h daily feeding, and total food deprivation conditions. Some hippocampal-ablated rats showed alterations of free-running rhythms under ad-lib feeding, but none of the ablations impaired the rats' ability to anticipate daily feeding, or 'remember' the phase of feeding time during subsequent food deprivation. Additional groups of intact rats were treated with the dopamine antagonist haloperidol (0.3 mg/kg or 2.0 mg/kg) 30 min prior to daily feeding, but this also did not prevent the emergence of food-entrained rhythms. The limbic and dopamine systems do not appear to play a necessary role in the generation or entrainment of food anticipatory circadian rhythms. PMID- 1590948 TI - Steady-state fluctuations of human walking. AB - In steady-state walking, fluctuations in space-time behavior are observed for normal adult subjects. In the present study, the intrinsic fluctuations of gait have been analyzed when walking on a subject-driven treadmill (with adjustable inertial forces). Furthermore, these intrinsic fluctuations have been compared with those observed in natural overground locomotion which involves a real subject's displacement and thus an optical flow. Four adult subjects participated in both experimental sessions. It was found that the frequency and amplitude of the instantaneous fluctuations of leg movement were weak and of equal magnitude with or without optical flow. This was also the case for instantaneous fluctuations in displacement speed. Secondly, a low-frequency fluctuation in walking speed was observed when no optical flow information was available to the subject. This fluctuation results from the addition of a series of leg-movement fluctuations, whose values are all either positive or negative. As the optical flow provides information about the displacement speed, it allows the subject to avoid such addition, and thus plays a role in maintaining steady leg movement. Theoretical models linking space-time behavior of rhythmic movement with stiffness strongly suggest that the observed low-frequency fluctuations in speed result from fluctuations in stiffness. PMID- 1590947 TI - Functional properties of dorsolateral prefrontal cortical neurons in awake monkey. AB - Electrophysiological single-cell responses were studied in 134 neurons in Walker's areas 46 and 9 of the prefrontal cortex of two stumptail macaques. The neurons were systematically tested for various visual, auditory and somatosensory stimuli. In addition, the rate of neuronal discharges were observed in relation to provoked or spontaneous eye or limb movements. More than half (52.2%) of the neurons responded to stimulation, and the majority of them gave visual responses. Eighty percent of the visual neurons responded to the presentation of various objects, the remaining being selective for meaningful objects or the appearance and movements of the experimenter. Auditory, somatosensory, somatomotor and oculomotor responses were also encountered; 9.0% of the recorded neurons were multimodal. Despite the large stimulus repertoire 47.8% of the neurons were found to be only spontaneously active. PMID- 1590949 TI - The effect of unilateral brain lesions on perception of visual illusions. AB - The study tested the effect of the left and right hemisphere lesions on the susceptibility to visual illusions. Twenty-five patients with left hemisphere damage, 22 patients with right hemisphere damage and 23 control subjects inspected series of figures producing four different illusions: Ponzo, Ehrenstein Orbison, Poggendorff and Zoellner. Series of stimuli configurations were constructed so that different degrees of distortion opposite to the illusory effect were introduced in each pattern. The amount of distortion was increased in steps so that at a certain point of the series the patterns produced percepts opposite to the illusory ones. That point indicated the strength of the illusion. Stimuli of a given series were presented to each subject 5 times in random order and subject's judgements of illusions were collected. The illusion strength was established using the Spearman distribution method for determining psychophysical thresholds. The results showed that the left and right hemisphere lesions either did not affect the subject's susceptibility to illusions (in Ponzo and Poggendorff) or their effects were similar, i.e. they reduced the strength of the perceived illusions (in Ehrenstein-Orbison and Zoellner). Our data contradict the hypothesis of hemisphere differences in the perception of visual illusions and support the view that those phenomena are multiple-caused. PMID- 1590950 TI - Development of a computerized system for simultaneous visual discrimination in rats. AB - In order to automate a simultaneous visual discrimination system, a Sutherland jumping-stand box was modified by adding two lateral alleys which connect the feeder compartment with the starting box. By means of a digital interface, this modified box was connected to an Apple IIe PC. A group of rats (n = 8) was trained. All subjects learned. Advantages relevant to the apparatus design, as well as the benefits derived from the automated procedure are discussed. PMID- 1590951 TI - Factors affecting habituation and recovery from habituation in the nematode Caenorhabditis elegans. AB - In four experiments, the factors that affect the rate of habituation, the degree of habituation, and the rate of recovery from habituation in a simple reflex circuit in Caenorhabditis elegans were investigated. The results showed that habituation was more pronounced and faster, and that recovery from habituation was more rapid, with short interstimulus intervals (ISIs) than with longer ISIs. Rate of recovery differed in animals that had reached asymptotic response levels when compared with animals still in the descending portion of the habituation curve. Once animals reached asymptotic response levels, rate of recovery appeared to be determined by ISI and not by additional stimuli. PMID- 1590952 TI - Presence of conspecifics facilitates learning that food is inedible in Aplysia fasciata. AB - The absence of a conspecific, but not of food, interfered with learning and memory of a feeding task in Aplysia fasciata. Interference was shown by a shortened training session and by lack of savings on retraining. The shortened training is not responsible for the lack of savings because brief training in the presence of a conspecific led to savings on retraining. Animals trained in the absence of a conspecific and then tested in its presence did not show signs of having learned, which indicates that the absence of a conspecific interfered with the ability to learn, rather than with the expression of memory. Absence of a conspecific also inhibited other aspects of feeding behavior, such as the latency to respond to food and the length of time that animals respond to food, which indicate that interference with learning was apparently caused by inhibition of feeding behavior, rather than by block of the mechanisms underlying learning. PMID- 1590953 TI - Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. AB - The contribution of the amygdala and hippocampus to the acquisition of conditioned fear responses to a cue (a tone paired with footshock) and to context (background stimuli continuously present in the apparatus in which tone-shock pairings occurred) was examined in rats. In unoperated controls, responses to the cue conditioned faster and were more resistant to extinction than were responses to contextual stimuli. Lesions of the amygdala interfered with the conditioning of fear responses to both the cue and the context, whereas lesions of the hippocampus interfered with conditioning to the context but not to the cue. The amygdala is thus involved in the conditioning of fear responses to simple, modality-specific conditioned stimuli as well as to complex, polymodal stimuli, whereas the hippocampus is only involved in fear conditioning situations involving complex, polymodal events. These findings suggest an associative role for the amygdala and a sensory relay role for the hippocampus in fear conditioning. PMID- 1590954 TI - Daily glucose injections facilitate performance of a win-stay water-escape working memory task in mice. AB - In an experiment that compared 3 versions of a working memory task, male C57BL/6 mice given either 3 (n = 7) or 5 (n = 7) opportunities (test runs) per trial to choose the escape choice section of a maze acquired a win-stay (spatial matching to-sample) water-escape task. Mice given only 1 test run per trial (n = 6) were unable to perform above chance level. In a 2nd experiment, 14 mice from the 1st experiment were tested for performance on the 3-test-run version of the task. Each mouse was tested for 12 consecutive days with each of 4 doses of glucose (0, 50, 100, & 250 mg/kg ip) given 30 min before testing. The two higher doses increased the percentage of correct test run choices on all 3 daily test runs across the 12 days of testing. Daily glucose injections facilitated the use of trial-dependent information. PMID- 1590955 TI - Cocaine-induced effects on isolation stress in neonatal rats. AB - The effects of cocaine administration on isolation-induced vocalizations and activity levels in 10-day-old rat pups were examined. Day 10 pups given cocaine (1.25, 2.5, 5, 10, & 20 mg/kg ip) vocalized significantly less than their caffeine- (10 mg/kg) and saline-administered siblings during a 5-min isolation period. Cocaine- and caffeine-administered pups also demonstrated a significant increase in overall activity compared with controls. In addition, intraperitoneal administration of the dopamine antagonist haloperidol (0.5 & 1.0 mg/kg) before 1.25 and 2.5 mg/kg cocaine produced a significant elevation in vocalizations compared with saline pretreatment, which indicates a blocking of cocaine's effect on calling behavior. These results suggest that the endogenous dopamine system involved with reinforcement and reward may quell the stress of isolation in the infant rat. PMID- 1590956 TI - Role of intrahypothalamic insulin in circadian patterns of food intake, activity, and body temperature. AB - These experiments examined the extent to which chronic intrahypothalamic (IH) insulin infusions that alter circadian patterns of food intake (FI) affect the regulation of other diurnally varying behavior in the rat. One-week IH insulin infusion (1.5 microU/hr) significantly decreases rats' night FI and increases day FI but does not alter the diurnal pattern of activity. Mean daily core temperature increased slightly but significantly during insulin infusion, the daily peak of the body temperature rhythm did not shift significantly, and the daily range of body temperature increased. IH insulin infusion in rats living in constant light and thus without circadian rhythm of FI led to significant decreases in FI and body weight. These data support the conclusion that IH insulin infusion alters food intake and body weight through a specific effect on a neural system that regulates food intake and body weight, and not by altering circadian rhythms. PMID- 1590957 TI - Low doses of haloperidol interfere with rat tongue extensions during licking: a quantitative analysis. AB - Orolingual dyskinetic effects of haloperidol were studied in rats trained to lick drops of water from a force-sensing disk. Haloperidol dose-dependently decreased force of tongue protrusion, decreased lick duration, increased interlick interval, and decreased number of licks. Fourier methods showed that haloperidol, in doses as low as 0.06 mg/kg, slowed the lick oscillations from an average of 5.250 Hz to 5.096 Hz (p = .014). Lick force was modulated by water drop delivery, but this effect was not influenced by haloperidol, which suggests no interference of the drug with sensory regulation of licking. The drug-induced deficits in tongue force may be manifestations of either postural alterations (pseudoparkinsonism) or orobuccolingual dyskinesias or both. Orolingual motor impairments may account for some of the neuroleptic-engendered behavioral decrements that have previously been explained in terms of reward, motivational deficits, or both. PMID- 1590958 TI - Pituitary-adrenal and dopaminergic modulation of schedule-induced polydipsia: behavioral and neurochemical evidence. AB - Five experiments investigated in rats the effects of increasing or decreasing plasma corticosterone levels on schedule-induced polydipsia and dopamine efflux in the nucleus accumbens. The results indicate that the acquisition of schedule induced polydipsia could be decreased by adrenalectomy, blockade of corticosterone synthesis, or administration of corticosterone. Performance of established schedule-induced polydipsia was also decreased by adrenalectomy. The effects of corticosterone administration on established schedule-induced polydipsia depended on the level of performance. High levels of drinking were enhanced by a high dose of corticosterone, whereas low rates of drinking were increased by a low dose. Similar injections of corticosterone also significantly increased dopamine efflux. The relative involvement of pituitary-adrenal activity and dopamine neurotransmission in the nucleus accumbens in the acquisition and performance of SIP is discussed and related to contemporary hypotheses of schedule-induced behavior. PMID- 1590959 TI - Effect of a social companion on the ultrasonic vocalizations and contact responses of 3-day-old rat pups. AB - Rat pups that are isolated in a novel environment emit ultrasonic calls. Vocalization in 3-day-old pups has been thought to be predominantly under thermal control (Allin & Banks, 1971). By the 2nd week of life, ultrasonic vocalizations are reduced when pups are tested in the company of a single anesthetized littermate (Carden & Hofer, 1990a; Hofer & Shair, 1978). In the present study, it was demonstrated that the vocalization rate of 3-day-old pups is also decreased when an anesthetized littermate is present in the isolation chamber. To determine whether this quieting was a function of the body heat of the companion, in a 2nd experiment, the axillary temperature of the companion was lowered until it was the same as the ambient temperature of the test chamber, 22 degrees C. In the presence of a cool companion, ultrasonic vocalizations were also reduced. For the last experiment, a textured plastic surrogate was substituted for the littermate. Calls were not diminished in the presence of the surrogate. PMID- 1590960 TI - Intracerebral oxytocin is important for the onset of maternal behavior in inexperienced ewes delivered under peridural anesthesia. AB - Measurement of cerebrospinal concentrations of oxytocin (OT) in intact and peridural-anesthetized ewes showed that central release of OT during parturition is inhibited by this anesthesia. Also, observations of maternal behavior and attraction to amniotic fluid (AF) in inexperienced peridural-anesthetized parturient ewes after intracerebroventricular injections of either OT (2 x 10 micrograms) or saline showed that OT infusions increased the proportion of maternal females (2/17 vs. 10/20; p = .01) and attraction to AF. This study confirms that in sheep vaginocervical stimulation activates the oxytocinergic system, which induces the onset of maternal behavior, and that this action is not limited to maternally experienced females. PMID- 1590961 TI - Partial callosotomy and left-right response differentiation in the rat: separate anterior and posterior facilitatory effects. AB - Earlier research demonstrated that complete section of the corpus callosum in the rat reduced the number of trials required to acquire a left-right response differentiation (LRRD). This study was designed to investigate whether the facilitatory effect on LRRD could be produced by section of an anatomical subdivision of the callosum. Rats with sections of the anterior or posterior corpus callosum mastered the LRRD task faster than sham subjects, but more slowly than rats with total callosal section; section of the middle portion of the callosum had no such effect. The partial facilitatory effects of anterior and posterior callosotomy appear to be independent, and suggest that the callosal intermixing of lateral information, which contributes to left-right confusion, occurs at both the sensory and motor levels of processing. PMID- 1590962 TI - Spinal cord stimulation in peripheral vascular disease. PMID- 1590963 TI - The congenital bregmatic dermoid: an African cyst? AB - Thirty-five children with bregmatic dermoids were operated on at the Red Cross War Memorial Children's Hospital and Groote Schuur Hospital between 1969 and 1990. Most children were under 1 year of age; 20 were males and 15 females. Thirty-one were African or of African descent, two were Indian and two Caucasian, an ethnic distribution which roughly approximates the ethnic ratio of patients attending our hospital. Most were investigated with skull X-rays and CT scan, but MRI was performed where further clarity was needed. Other lesions mimicking bregmatic dermoids included four haemagiomas, two hamartomas, two lipomas and one encephalocoele through the anterior fontanelle. One bregmatic lipoma was associated with a lipoma of the corpus callosum. All bregmatic cysts were removed through a simple elliptical incision and on connection with the central nervous system or its coverings was encountered in any patient. The pathology in all specimens reviewed (75%) revealed skin appendages to be present in the cyst wall. No epidermoids were found in this series. This series is the largest to date and adds another 31 patients of African descent to the accumulated literature which suggests that although universally distributed, the bregmatic dermoid still appears to be more common in Africans or their descendants. PMID- 1590964 TI - Complications of intrathecal baclofen delivery. AB - The medical records of 46 consecutive patients who have had intrathecal Baclofen drug delivery systems implanted in the National Spinal Injuries Centre, the Paddocks Hospital Spinal Unit, Princes Risborough, Lodge Moor Hospital Spinal Unit, Sheffield, the Northern Regional Spinal Injuries Unit, Hexham and The Radcliffe Infirmary, Oxford, were reviewed. Patients were contacted to describe their views on the treatment. The complications of the treatment are described. Some, such as overdose and meningitis are particularly hazardous. Others, in particular pump tubing revisions, are more of an inconvenience and time consuming for the patient and physician. If the serious risks of this valuable treatment are to be minimized and the therapy applied most effectively than a well co ordinated team is essential, involving in particular the physician responsible for the initial assessment and follow-up of the patient and an experienced surgeon. It is recommended that only a small number of centres in the UK undertake these implants. PMID- 1590965 TI - The influence of alcoholism on outcome after evacuation of subdural haematoma. AB - The postoperative course and final outcome after evacuation of subdural haematoma are described in 106 male patients in relation to their alcohol consumption. One third of the patients were alcohol abusers, drinking at least 60 g of ethanol daily. Despite comparable head trauma, they had a significantly higher incidence of acute subdural haematomas and showed increased postoperative morbidity and mortality compared to the non-alcoholics. The postoperative hospitalization costs were initially higher and the final outcome was significantly worse for the alcohol abusers. PMID- 1590966 TI - Intracranial tumours in the elderly: the effect of age on the outcome of first time surgery for meningiomas. AB - We have investigated the effect of age on the outcome of first time surgery for intracranial meningiomas. In a retrospective study, 144 consecutive patients were divided into three groups: young (up to 44 years of age, 38 patients), middle aged (45-64 years, 60 patients) and elderly (65 years and over, 46 patients). Outcome was assessed at the first follow-up appointment 4-6 months after discharge. The surgical mortality was 2.7%. The incidence of significant intercurrent disease increased with age (11, 25 and 35%, respectively), as did the incidence of postoperative complications (16, 23 and 30%). Postoperative intracranial bleeding was especially age-related, occurring in 20% of the elderly group as against 0% of the younger. Although the younger patients did best (100% in Glasgow Outcome Scale Grade 5) there was no difference in outcome between the middle-age and elderly groups (88 and 83%, respectively). Of the elderly patients, 89% showed clear functional improvement after surgery, 2% were unchanged and 9% were worse or dead. The intellectual deterioration apparent in over half of the elderly patients recovered after removal of the tumour in 80%. We conclude that age has little effect on the prospects of success after removal of an intracranial meningioma. PMID- 1590967 TI - Intracranial lipomas: current perspectives in their diagnosis and treatment. AB - Intracranial lipomas are very rare lesions, which are probably congenital. Though they can occur anywhere in the intracranial space, a high proportion of cases tend to be ++located around the midline. They are usually asymptomatic. When symptoms do occur, they are frequently the result of co-existing general clinical conditions. Lipomas used to be reported mainly as incidental findings at autopsy, but advances in neuroimaging techniques have greatly improved the likelihood of their being discovered during life. Surgical extirpation is not necessary in the majority of patients, many of whom show remarkable clinical improvement following shunt procedures for obstructive hydrocephalus (when present) as well as vigorous treatment of co-existing conditions. PMID- 1590968 TI - High-dose dexamethasone therapy in head injury: a patient group that may benefit from therapy. AB - Three patients with head injuries and focal areas of low density on CT who deteriorated progressively with uncontrollable rising intracranial pressure (ICP) are described. High-dose dexamethasone therapy was followed by a substantial decrease in ICP during the following 24 h. Features that the patients had in common are a young age group, an initial GCS of 10 or more and an elevation of ICP 2 days or longer after admission. PMID- 1590969 TI - Cavernomas of the spinal cord: report of two patients. AB - Two operated cases of spinal cord cavernomas are presented. Since spinal angiography is usually normal and myelography not specific, the contribution of magnetic resonance imaging to the diagnosis is emphasized. Surgical considerations of treatment are discussed. PMID- 1590970 TI - Recurrent dysplastic cerebellar gangliocytoma (Lhermitte-Duclos disease) presenting with subarachnoid haemorrhage. AB - A case of dysplastic cerebellar gangliocytoma recurring after 20 years and representing with subarachnoid haemorrhage is described. Evidence in favour of a neoplastic pathogenesis is presented. PMID- 1590971 TI - Foci of extramedullary haemopoiesis in a cerebellar haemangioblastoma. AB - A posterior fossa haemangioblastoma is described which contained foci of extramedullary haemopoiesis. Although secondary polycythemia has been reported with a frequency of between 5 and 30% in patients with haemangioblastomas only five cases have been described previously in the English literature where haemopoietic tissue was identified in the tumour. PMID- 1590972 TI - Solitary ectopic intracerebral schwannoma. AB - Intracerebral Schwannoma is a rare tumour which can mimic meningioma clinically, radiologically and morphologically. Immunohistochemical techniques are necessary to confirm the Schwann cell origin of the tumours. We report such a tumour in the posterior frontal parasagittal region. The origin of Schwann cells in the central nervous system is still speculative and various postulations are discussed. PMID- 1590973 TI - Is skull X-ray necessary after milder head trauma? PMID- 1590974 TI - Equilibrium "wetting" of surfaces by membrane-covered vesicles. AB - "Wetting" of surfaces by thin-membrane capsules is the central process involved in coagulation of suspensions of surfactant membrane vesicles and other-related phases of microemulsions. Although equilibrium "wetting" by membrane capsules appears similar to the macroscopic wetting by liquid droplets, there are important differences: i.e. membrane tension (in place of liquid-interfacial tension) and "effective" contact angle are not fixed constants. Since membranes are condensed-cohesive materials with limited permeability, geometric restrictions (surface area and enclosed volume) are the principal determinants of the extent of contact with a substrate (and "effective contact angle) for "strong" adhesion energies. Deviation from this universal feature arises when membrane-membrane attraction becomes sufficient to compete with membrane substrate attraction; a transition is predicted from maximal contact with the substrate to partial substrate contact plus membrane lamination by self adhesion. Following the transition, the "effective" contact angle is determined by the ratio of self adhesion: substrate adhesion energies. A critical condition is established for the transition by the area excess (over a sphere of equivalent volume). Because of the exceptional flexibility of fluid membranes, thermal excitations produce long-wavelength collective motions and significant shape fluctuations. Restriction of fluctuations (by area: volume constraints and adhesion) lead to unconventional elastic response and crossover from "strong" to "weak" regimes of equilibrium "wetting" for membrane capsules. PMID- 1590975 TI - The role of the Y-chromosome in sex determination. AB - The basic plan of gonadal development in both sexes is female unless testes are induced by factor(s) of the Y chromosome, known as testis determining factor(s) (TDF). It is not clearly established whether the Y chromosome control is autonomous or under the control of a gene on the X chromosome or autosomes. A gene for the H-Y antigen (Histocompatibility-Y antigen) has been postulated to be the factor determining testicular differentiation. Recent studies have demonstrated that the gene for testis determination and the H-Y determinant are two separate entities. Although earlier cytogenetic observations localized TDF on the pericentric region of the short arm of the Y chromosome, subsequent findings by high-resolution chromosome banding and molecular analysis localise TDF to the distal part of the short arm of the Y chromosome, adjacent to the pseudoautosomal region. A candidate for TDF, the ZFY, was localised within the 140 kb interval where the position of TDF was defined, and considered as the TDF gene. However, a smaller gene sequence of 35 kb, the SRY, situated outside the 140 kb ZFY region, has recently been isolated and proved to be the only and the smallest part of the Y chromosome necessary for male sex determination. PMID- 1590976 TI - The cardio-facio-cutaneous (CFC) syndrome: autosomal dominant inheritance in a large family. AB - A large, three generation-family with firm evidence of autosomal dominant transmission of the cardio-faciocutaneous (CFC) syndrome is reported. This observation questions once more the validity of separating the CFC syndrome from the Noonan syndrome as two distinct entities. PMID- 1590977 TI - Madelung deformity as a pathognomonic feature of the onycho-osteodysplasia syndrome. AB - On the occasion of the observation of the Onycho-osteo-dysplasia syndrome (HOOD syndrome--Nail-Patella syndrome) in a 4-generation family we were impressed by the presence of a Madelung deformity in the four examined family members. A critical review of the literature showed that a true Madelung deformity was present in a great number of previously reported patients but that no specific attention was given to this apparently important symptom. PMID- 1590978 TI - Familial occurrence of unilateral biphalangeal duplication of the thumb. AB - Duplication of the thumb is not an uncommon condition and the biphalangeal type is considered to be a sporadic event. We report the familial occurrence of a unilateral thumb polydactyly type 4 of Wassel (12) or preaxial polydactyly type 1 of Temtamy (11). PMID- 1590979 TI - Arthrogryposis, ectodermal dysplasia and other anomalies in two sisters. AB - Ectodermal dysplasia with arthrogryposis is an uncommon condition. We describe two daughters of a distant consanguineous couple with oligodentia, enamel abnormalities, camptodactyly, longitudinally broken nails, growth retardation, joint contractures with amyotrophy, hypohidrotic skin with tendency to excessive bruising and scarring after injuries and scratching, kypho-scoliosis, mild facial dysmorphia and microcephaly. The condition is probably due to an autosomal recessive gene, the parents being gypsies of the same ancestral origin. PMID- 1590980 TI - Tau syndrome (thrombocytopenia and absent ulnar) with mental retardation and facial dysmorphy. AB - A girl with pancytopenia (hemoglobin 9 g. 2,000 PMN. 75,000 platelets) was examined at 23 years of age. She had microcephaly, facial dysmorphy, skeletal deformities (kypho-scoliosis, club feet, club hands) and mental retardation. Puberty was normal, Roentgenograms showed bilateral agenesia of the distal part of the ulna with dislocation of the head of the radius. No other skeletal parts were absent. The condition is probably due to an autosomal recessive gene, the parents being second cousins. PMID- 1590981 TI - Minimal dysmorphic stigmata in 9q deletion of paternal origin. AB - In this report, we describe a 6 month old girl with a "pure" deletion 9 (pter--- p22:) of paternal origin and very discrete facial dysmorphism as the only minimal phenotypic expression of the chromosomal imbalance. We hypothesize that the phenotypic expression in pure 9p deletion may depend from its parental origin. PMID- 1590982 TI - Intrauterine growth retardation, mild frontonasal dysplasia, phocomelic upper limbs with absent thumbs and a variety of internal malformations including choanal atresia, congenital heart defects, polysplenia, absent gall bladder as well as genitourinary anomalies. A possibly "new" MCA syndrome? AB - Report on a female infant who showed intrauterine growth retardation; dysmorphic face with relative macrocephaly, mild frontonasal dysplasia, and small dysmorphic ears; phocomelic upper limbs with absent thumbs and radiologically poor differentiation of the long tubular bones but normal lower limbs. Autopsy revealed multiple internal abnormalities including choanal atresia, complex heart malformation, bilobed lung on the right, polysplenia, absent gall bladder as well as genitourinary anomalies. This condition represents a possibly "new" MCA syndrome with poor prognosis and yet unknown etiology. PMID- 1590983 TI - Dysmorphology report holoprosencephaly-polydactyly syndrome: affected brother and sister with a wide spectrum of anomalies. PMID- 1590984 TI - Sequences and factors: a guide to MHC class-II transcription. AB - The expression of the class-II antigens of the major histocompatibility complex is tissue-specific, developmentally regulated in cells of the B lineage, and inducible by cytokine. Some of the molecular mechanisms that account for this regulation have recently been elucidated. DNA sequences upstream of human and mouse class-II genes that are critical for the transcription of these genes have been identified through transfection studies and transgenic analysis. Furthermore, a number of transcription factors that bind to important promoter motifs have recently been isolated. Examination of the class-II promoter in vivo both in the normal state and in patients with bare lymphocyte syndrome has further increased our understanding of class-II regulation. PMID- 1590985 TI - Murine natural killer cells and marrow graft rejection. AB - Rejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant in marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3-, NK1.1+), cytotoxic T cells (CD3+, CD8+), and T cells with natural killer cell markers (CD3+, NK1.1+) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented. PMID- 1590986 TI - Molecular approaches to analysis of X-linked immunodeficiencies. AB - Although the X-linked immunodeficiencies--X-linked agammaglobulinemia (XLA), X linked severe combined immunodeficiency (XSCID), Wiskott-Aldrich syndrome (WAS), X-linked lymphoproliferative syndrome and X-linked hyper IgM syndrome--have been mapped to loci distributed throughout the X chromosome, they have several features in common that suggest that they might be members of a gene family: (i) all are maintained in the population at approximately the same gene frequency; (ii) expression of each defect is limited to the hematopoietic system; (iii) atypical forms of each disorder have been described; and (iv) obligate carriers of these disorders are normal by all immunologic criteria. The failure of carriers of XLA, XSCID, and WAS to show signs of their gene defects can be explained by the preferential use of the normal, nonmutant X as the active X in the cell lineages affected by the gene defects. These three disorders also share an additional feature; in boys with XLA, XSCID, or WAS there is asynchronous expression of cell surface markers of differentiation or activation. If some or all of the genes that are abnormal in the X-linked immunodeficiencies are members of a gene family, then isolation of one gene may lead to the others. PMID- 1590987 TI - In vitro antibodies: strategies for production and application. AB - The approaches to the production of antibodies (Ab) using the techniques of genetic engineering and expression are reviewed. Genetic engineering facilitates the production of proteins tailormade for an intended use. Bacterial and mammalian expression systems are commonly used for the production of Ab and Ab like molecules. While genomic or cDNA cloning can be used to obtain the relevant variable regions, PCR-based cloning approaches facilitate the acquisition of additional binding specificities. Large numbers of different chimeric Abs with murine variable regions joined to constant regions from human and other species have been expressed and found to exhibit the expected binding specificities and effector functions. These molecules have been used to study the structural basis of effector functions such as complement activation and Fc receptor binding, and potentially they may be used as therapeutic agents. Carbohydrate has been shown to influence both variable and constant region function. Single-chain Abs and fusion proteins with Ab binding specificities joined to nonimmunoglobulin sequences provide a source of Ab-like molecules with novel properties, and genetically engineered Ab-like molecules provide a source of useful antigens. Combinatorial libraries produced in bacteriophage present an alternative to hybridomas for the production of Abs with desired combining specificities. Issues of the immunogenicity of the recombinant molecules are addressed. PMID- 1590988 TI - Apoptosis and programmed cell death in immunity. AB - Death of some cells in the mammalian body is clearly programmed. In the immune system there are many examples of programmed cell death, during development of lymphocytes as well as at later stages, after interaction with antigen. Many of these examples display the morphology of apoptosis: They undergo shrinkage and zeiosis, the nucleus collapses, and chromatin is cleaved into nucleosomal fragments. The cell is rapidly recognized by phagocytes and disposed of without releasing its contents. In some but not all cases of apoptosis, new macromolecular synthesis is required. Cytotoxic T cells induce changes in their targets that are morphologically apoptotic. The mechanism of apoptosis is currently under active investigation. PMID- 1590989 TI - Cytokine receptors and signal transduction. AB - Cytokines play a vital role in coordinating immune and inflammatory responses. Unlike growth factor receptors with a tyrosine kinase, cytokine receptors have no intrinsic tyrosine kinase activity. Based on their structure, cytokine receptors are classified into several groups. High affinity receptors for IL-2, IL-3, IL-5, IL-6, and GM-CSF are composed of at least two distinct subunits, alpha and beta. The alpha subunits are primary cytokine binding proteins, and the beta subunits are required for formation of high affinity binding sites as well as for signal transduction. The GM-CSF, IL-3, and IL-5 receptors appear to share the same beta subunit in human, and therefore cross-talk among these cytokines may occur at the receptor level. High affinity receptors presumably are linked to various signal transduction pathways that lead to different cytokine functions. Differential expression of the cytokine receptors as well as reorganization of intracellular signalling pathways are critical for development of hemopoietic cells. PMID- 1590990 TI - Cellular basis of skin allograft rejection: an in vivo model of immune-mediated tissue destruction. AB - Rejection of transplanted tissue allografts results from T-cell recognition of histocompatibility antigens expressed by cells of the donor graft. This review focuses on the phenotype, specificity, and function of the T cells mediating rejection responses against skin allografts, and on the immune mechanisms by which host T cells are either activated or rendered non-responsive by cellular populations within the graft. We review the cellular basis for rejection responses across limited class-I and class-II major histocompatibility differences, as well as the specificity of the rejection response itself. PMID- 1590991 TI - V(D)J recombination: molecular biology and regulation. PMID- 1590992 TI - Regulation of immunity to parasites by T cells and T cell-derived cytokines. AB - Parasitic protozoa and helminths are a diverse group of organisms which together form a major cause of infectious disease in humans and livestock. Studies in animal models have revealed that T lymphocytes and the cytokines they produce play a crucial role in determining the outcome of parasitic infection in terms of both protective immunity and immunopathology. Of particular interest is recent evidence that different parasitic infections in the context of different host genetic background can trigger polarized CD4+ T cell subset responses. The set of cytokines produced by these different T helper responses, in turn, can have opposing effects on the parasite, resulting in either control of infection or promotion of disease. Moreover, cytokines produced by one CD4+ subset can block either the production and/or activity of the cytokines produced by the other subset. The establishment of this state of cross-regulation may be important for parasite survival. CD8+ T cells also appear to play a dual effector/regulatory role in parasite immunity and immunopathology, although the mechanisms underlying their induction and function are less well understood. CD(8+)-mediated cytolytic killing functions have now been demonstrated against a number of different intracellular protozoa, although IFN-gamma produced by the same effector cells may also be critical in host community. In addition to providing highly relevant models for studying the selection and immunobiologic function of T-cell subsets, research on T lymphocyte-parasite interactions is crucial for the design of effective vaccines and immunotherapies and thus has broad practical as well as theoretical ramifications. PMID- 1590993 TI - The pathophysiology of tumor necrosis factors. PMID- 1590994 TI - Transgenic mice and analysis of B-cell tolerance. AB - Understanding the mechanism of immunological tolerance to self-antigens remains a fundamental problem in immunology. Transgenic mice carrying rearranged antigen receptor genes have provided a window into the events involved in this process, by allowing the development and fate of antigen-specific lymphocytes to be followed in vivo. In the B-cell lineage, as in T cells, self-reactive cells have been found to undergo several distinct fates in vivo: they can be physically eliminated, functionally inactivated, or they can persist unchanged or become activated. As discussed in this review, direct visualization of the fate of self reactive cells resolves one of the key issues in tolerance. Achieving a precise understanding of the cellular and molecular events leading to lymphocyte deletion, anergy, or activation nevertheless remains a challenge for the future. PMID- 1590995 TI - Peripheral T cell tolerance. AB - The most efficient way to ensure self-tolerance in the T-cell repertoire is by intrathymic deletion of self-reactive clones. Antigens not present intrathymically may, however, influence the peripheral T-cell pool in various ways. The may of course activate T cells, provided that these have the correct specificity and affinity and that the antigens are presented in sufficient amounts on professional antigen-presenting cells. They may be ignored by T cells if some of these conditions are not met. In some forms, the antigen may be toleragenic for mature T cells. If the antigens persist in an immunogenic form, unresponsiveness may eventually be imposed as the end result of a powerful immune response. Extrathymic self-antigenic components are generally encountered early in development, and the way in which these influence peripheral T lymphocytes has been studied by transgenic technology. They may be ignored by T cells if they are sequestered from the immune system, or if they are present in low amounts or on nonprofessional antigen-presenting cells which lack the appropriate accessory molecules or signals needed to activate the relevant T-cell subset. On the other hand, some of these self-antigens readily induce anergy in peripheral T cells, which may or may not involve downregulation of antigen receptors and coreceptors. Tolerance in the T-cell repertoire is therefore achieved not only by intrathymic deletion of self-reactive clones but also by several postthymic mechanisms. PMID- 1590996 TI - Physiological and molecular mechanisms of lymphocyte homing. AB - The lymphoid system is functionally compartmentalized in vivo into discrete primary, secondary, and tertiary lymphoid organs. Primary lymphoid tissues--the bone marrow and thymus--are responsible for the production of mature "virgin" lymphocytes. Secondary lymphoid tissues--lymph nodes, the spleen, and gut associated lymphoid tissues--are specialized for the accumulation and presentation of antigen to both virgin and memory lymphocyte subsets. The remainder of the body's tissues may be considered "tertiary" lymphoid tissues, in that they normally contain only a few lymphoid elements, but in the setting of inflammation can be induced to recruit unique subsets of primarily memory lymphocytes. Each lymphoid tissue is further subdivided into discrete microenvironments, each characterized by a distinct complement of lymphocyte subsets and stromal cells. Lymphocyte homing comprises the physiologic processes by which lymphocytes seek out and localize to particular tissues and to specific microenvironments therein. Homing mechanisms play a major role in the maintenance of these specialized microenvironments and are critical for the dispersal and targeting of naive and memory lymphocyte populations that are required for effective immune surveillance. Here, we provide a brief overview of mechanisms thought to control the homing of lymphocyte populations in vivo, focusing in particular on the adhesive interactions involved in lymphocyte-endothelial cell recognition and in the selective extravasation of lymphocyte populations into secondary and tertiary lymphoid tissues. PMID- 1590997 TI - Restricted VH gene usage and generation of antibody diversity in rabbit. AB - The presence of VHa allotypic specificities on nearly all rabbit Ig molecules has perplexed immunologists for many years. How could these allotypic specificities be inherited as if controlled by alleles if the germline has hundreds of VHa allotype-encoding genes and if most of these genes are used in VDJ gene rearrangements. I review recent data indicating that the allelic inheritance of the VHa allotypes can be explained by preferential utilization of the D-proximal VH gene VH1 in VDJ gene rearrangements. The preferential usage of one VH gene, however, limits the contribution of combinatorial joining of multiple VH, D and JH gene segments to the generation of antibody diversity. The roles of somatic gene conversion and somatic mutation in generating antibody diversity are discussed. Further, the limited usage of germline VH genes in normal, allotype suppressed and the mutant Alicia rabbit as well as the molecular basis of latent allotypes and VH/CH recombinants is reviewed. PMID- 1590998 TI - Tumor antigens. AB - This review solidifies a new concept that common and rare types of human cancers harbor a variety of tumor-specific mutant proteins that may be recognized as tumor-specific antigens. These mutant proteins are encoded by oncogenes or suppressor genes that have undergone structural mutations resulting from point mutations, chromosomal translocations, internal deletions and viral insertional mutagenesis; several of these changes result in fusion proteins. While there is no evidence that immunosurveillance against these mutant proteins can prevent the development of primary cancers without prior immunization of the host, such tumor specific molecules might be important for diagnosis and as targets for specific immunotherapy once the cancer has developed or even as targets for preventive cancer vaccines. Evidence further supports the notion that cytolytic or helper T cells are exquisitely selective in recognizing intracellular mutant proteins, and tumor-specific T cell clones presently available may become useful for identifying previously unrecognized tumor-specific mutations. Many tumor-specific mutant proteins clearly play a causative role in the establishment of malignant behavior, whereas other carcinogen-induced changes have at least immunological relevance. In any case strong evidence in mouse and man indicates that a single malignant cell can express multiple independent antigenic target sites. Such multiplicity may allow a multi-pronged immune attack that substantially decreases the chance of tumor escape. Future work must explore whether immune responses to tumor-specific mutant proteins can lead to immunological tumor rejection and explore the possibility of chemically engineering tumor mutant peptides to be highly immunogenic, even in hosts that have previously failed to respond to the tumor. PMID- 1590999 TI - Immune receptors: targets for therapy of leukemia/lymphoma, autoimmune diseases and for the prevention of allograft rejection. AB - Immune receptor-directed therapy has been applied clinically to an array of human disorders. However, effective therapy using unmodified murine monoclonal antibodies was elusive because these antibodies are immunogenic and elicit a human immune response, are not cytocidal against human cells, and in most cases are not directed against a cell surface structure required for proliferation and survival. Recently therapy mediated by monoclonal antibodies has been revolutionized by the definition of cell surface structures as targets for effective monoclonal antibody action, the creation by genetic engineering of less immunogenic and more effective monoclonal antibodies, and by the arming of such antibodies with toxins and radionuclides. Furthermore, other therapeutic agents directed toward immune receptors have been developed, including cytokine-toxin fusion proteins as alternative vehicles to address abnormal receptor-expressing cells, soluble immune receptors and naturally occurring receptor antagonists as immunomodulators, and T cell antigen receptor peptides as immunogens to provide protection against autoimmune diseases. Thus, the new insights concerning the structure and function of lymphocyte cell surface receptors and the development of different modalities of receptor-specific therapy are providing new perspectives for the treatment of human leukemia/lymphoma, autoimmune and graft vs-host diseases, and for the prevention of allograft rejection. PMID- 1591000 TI - Altering genes in animals by gene targeting. AB - It is possible to create mice in which a planned alteration has been introduced at a specific locus in the genome. The planned alteration is first introduced into the genome of mouse embryonic stem (ES) cells in tissue culture. This is accomplished by homologous recombination between the targeted genomic locus and DNA introduced into the ES cells. Cells containing the desired alteration are injected into recipient blastocysts for return to pseudo-pregnant foster mothers, where they can develop into chimeric pups. ES cells that contribute to the germline of the resulting chimeric mice allow the altered ES cell genome to be transmitted to future generations. This technique provides a powerful tool for exploring the mechanisms underlying the development and function of the immune system in vivo. PMID- 1591001 TI - The human T cell receptor in health and disease. AB - The T cell antigen receptor (TCR) recognizes antigen in the form of short peptides bound to a major histocompatibility (MHC) molecule. This review provides a synopsis of the current state of knowledge of the structure and function of the receptor and its possible role in human disease. Analysis of the T cell receptor usage of T-cell lines and clones recognizing the same peptide-MHC complex is beginning to shed light onto the structural basis of the TCR-peptide-MHC complex. Also, it is now apparent that there are two mechanisms by which the TCR can interact with the MHC molecule, either through classical peptide interactions or through super-antigens. Finally, we review the role of specific TCRs in human disease. Current evidence in this area is difficult to interpret; however, it is likely that TCR-mediated disease susceptibility exists, and its basis at either a germline or somatic level will soon be clarified. PMID- 1591002 TI - The role of somatic mutation in the pathogenic anti-DNA response. AB - Anti-DNA antibodies represent a significant autospecificity in systemic lupus erythematosus because they are essentially diagnostic of the disease and they contribute to renal pathology. The molecular genetic characterization of these antibodies from both lupus-prone mice and humans with lupus has shown them to be somatically mutated. In many cases the nature of the mutations suggests that DNA or some structurally homologous molecule is driving the response. In other cases the high replacement-to-silent mutation ratio in framework regions of the antibody suggests selection by idiotype or by some mechanism other than antigen itself. Current studies of immunoglobulin variable region genes encoding anti-DNA antibodies reveal no disease associated polymorphisms. There are also no data suggesting that the nature of the recombination process that forms intact variable region genes or of the process of somatic mutation differs in autoimmune and nonautoimmune strains or kindred. Current data suggest, rather, that a defect in regulation is responsible for auto-antibody production in SLE. The finding that most if not all anti-double stranded DNA antibodies are somatically mutated suggests the defect is in maintenance of peripheral rather than central tolerance. PMID- 1591003 TI - Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. AB - Chromosomal translocation within B and T cell malignancies has proven a rich source for proto-oncogenes. The obligate DNA breaks within immunoglobulin (Ig) and T cell receptor (TCR) loci are frequently the sites of recurrent translocations. Burkitt's lymphoma established the paradigm by introducing the myc oncogene from chromosome segment 8q24 into the Ig heavy chain gene locus at 14q32. Molecular cloning of an aberrant Ig rearrangement in follicular lymphoma revealed Bcl-2. Bcl-2 constitutes the first member of a new category of oncogenes: regulators of programmed cell death. Bcl-2 blocks apoptosis and maintains long-term immune responsiveness including B-cell memory. The PRAD1 gene of parathyroid adenomas appears to be the elusive Bcl-1 gene of t(11;14)(q13;q32) bearing lymphomas. It proves to be a novel G1 cyclin. Acute lymphoblastic leukemias (ALL) pre-B phenotype produce a E2A/PBX fusion protein that possesses the leucine zipper of E2A with the homeodomain of PBX. Two molecular forms of the BCR/ABL fusion protein are produced by the Philadelphia chromosome. A deregulated p210 tyrosine kinase is found in chronic myelogenous leukemia, while a p190 form predominates in Ph+ ALL. In contrast, T-cell ALLs introduce a potpourri of genes into their T cell receptor loci. However, a common theme is emerging. These oncogenes (Ttg1, Ttg2, SCL, LylI, H0X11) all belong to classic families of transcription factors, possessing LIM domains, helix-loop-helix motifs, or homeodomains. Provocatively, these transcription factors are normally intended for lineages other than T cells. These genes have widened the horizons of both oncogenesis and normal development. PMID- 1591004 TI - Complement deficiencies. AB - The complement system consists of about two dozen plasma and cell membrane proteins which function as cofactors in defense against pathogenic microbes and in the generation of many immunopathogenic disorders. The complexity of this system and its role in other biological functions has been appreciated within the last two decades. Recognition of genetic deficiencies of the complement proteins and their phenotypic expression has provided additional insights into the physiological role of the complement system. Complementary DNA (cDNA) clones for most of the complement components are now available, and the gene structures for many have been elucidated. Application of molecular biological methods to studies of the complement system and its deficiencies has permitted both the determination of primary structure and chromosomal localization of complement genes (Figure 1) and the capacity to elucidate the molecular basis of complement deficiency disorders. PMID- 1591005 TI - Molecular components of T-cell recognition. AB - We review recent data that increase our understanding of the ternary complex of the T cell receptor (TCR), antigenic peptides, and molecules of the major histocompatibility complex (MHC). Studies using synthetic peptide analogs for T cell antigens have identified peptide residues that appear to interact with the MHC molecule and/or the TCR. The logical extension of these studies, using a complete replacement set of peptide analogues for a model peptide antigen, has more precisely defined the biochemical character of putative MHC and TCR contact residues, and indicated that the TCR is highly sensitive to subtle changes in peptide conformation. Insight into the binding site for peptide on the TCR has recently come from variant peptide immunization of TCR single-chain transgenic mice. These experiments indicate that residues encoded by the V(D)J junctions of both TCR chains contact peptide directly. TCR-MHC contacts have also been studied, using in vitro-mutagenized MHC molecules, particularly those altered at residues predicted to point "up," toward the TCR. These studies reveal that TCR MHC contacts appear to be quite flexible, and vary between even closely related TCRs. A measure of the affinity of TCR for peptide/MHC complexes has come from competition experiments using soluble MHC complexed with specific peptides. This affinity, with a KD of 5 x 10(-5) M, is several orders of magnitude lower than that of most antibodies for their protein antigens and suggests that the sequence of events leading to T-cell activation begins with antigen-independent adhesion. PMID- 1591006 TI - Antigen receptors on B lymphocytes. AB - Recent studies on the structure of the B cell antigen receptor demonstrate that the membrane-bound and antigen-binding immunoglobulin molecules are noncovalently associated with a heterodimer of two novel transmembrane proteins. The B cell antigen receptor is thus a multicomponent receptor complex whose structural features are similar to those of the T cell antigen receptor complex. Cross linking of the B cell antigen receptor results in rapid tyrosine phosphorylation of substrate proteins. This suggests that the B cell receptor belongs to a subgroup of the tyrosine kinase receptor family with a noncovalently associated src-like tyrosine kinase. PMID- 1591007 TI - Suppression of human alveolar macrophage-derived cytokines by amiloride. AB - Various human alveolar macrophage (AM)-derived cytokines in the lungs have been shown to be present under conditions of normal homeostasis as well as during the pathogenesis of inflammation. Although extensive investigation has demonstrated the induction of cytokines from AM, relatively little is known regarding endogenous and exogenous regulation of their production. Several pharmacologic agents, including corticosteroids, cyclooxygenase inhibitors, prostaglandins, and methyl-xanthines have been examined for their role in the modulation of mononuclear phagocyte-derived cytokines. In this study, we examine the role of amiloride for the regulation of AM-derived interleukin (IL)-8, tumor necrosis factor (TNF), IL-6, and IL-1 beta. Amiloride in concentrations of 10(-4) to 10( 6) M, concentrations capable of being achieved in the distal airways via nebulization, were shown to inhibit lipopolysaccharide-stimulated, AM-derived IL 8 and TNF in both a time- and dose-dependent fashion. In addition, 5-(N,N hexamethylene) amiloride hydrochloride, an amiloride analogue with specific sodium channel antiport inhibition, resulted in a similar dose-dependent suppression of lipopolysaccharide-stimulated, AM-derived IL-8 production. Furthermore, the suppressive effect of amiloride appeared to be at the level of mRNA for IL-8, TNF, IL-1 beta, and IL-6, whereas steady-state levels of beta actin mRNA remained unaltered. These findings would suggest that amiloride has a potentially important modulating influence for the regulation of AM-derived cytokines. PMID- 1591008 TI - Surfactant protein C is expressed in alveolar type II cells but not in Clara cells of rat lung. AB - The expression of the surfactant-associated proteins in bronchiolar cells remains to be defined. We used in situ hybridization to identify sites of message expression of the surfactant-associated proteins A, B, and C (SP-A, SP-B, and SP C) in adult and fetal rat lung. The expression of these messages by in situ hybridization was also compared with the localization of SP-A by immunocytochemistry. The localization of SP-A was used to identify type II cells and nonciliated bronchiolar epithelial (Clara) cells in these sections. The cRNA antisense probes for SP-A, SP-B, and SP-C appeared to hybridize over type II cells. Sense probes showed no localization or apparent specific hybridization. Messages for both SP-A and SP-B were also found in nonciliated bronchiolar epithelial (Clara) cells. However, no message for SP-C was observed in these cells. Clara cells from terminal to large bronchioles lacked detectable mRNA for SP-C. Expression of surfactant protein mRNAs was not detectable in type I cells, alveolar macrophages, interstitial cells, or vascular cells. Similarly, in fetal rat lung the messages for SP-A and SP-B but not SP-C were detected in bronchiolar cells. We conclude that rat Clara cells do not express SP-C mRNA, and thus SP-C can be regarded as a specific marker for rat type II cells. PMID- 1591009 TI - The C-terminal domain of the pulmonary surfactant protein C precursor contains signals for intracellular targeting. AB - We have studied the intracellular transport of the pulmonary surfactant SP-C precursor in vitro and in vivo. In order to monitor the route of the SP-C precursor, we constructed various C-terminally truncated forms of SP-C, which were tagged with a sequence derived from the C-terminus of the human c-myc gene (aa 409-419). Expression of these constructs under the control of the SV40 enhancer and the huMT-II promoter in stably transformed Chinese hamster ovary (CHO) cells revealed that the complete precursor molecule is localized mostly in vesicular structures, probably of lysosomal origin. The truncated precursor lacking the last 22 amino acids at the C-terminus (SP-C/Ctag), however, was restricted to the endoplasmic reticulum as shown by immunofluorescence, using antibodies directed against the tag-sequence, the lysosomal enzyme cathepsin D, the enzyme disulfide isomerase, and the Golgi zone. The intracellular localization was substantiated by subcellular fractionation analysis, suggesting that the last 22 amino acids are necessary for intracellular targeting. Furthermore, Triton X-114 extractions from CHO cells revealed a modification of the SP-C precursor. In vitro translation and pulse-chase experiments in the absence or presence of microsomes showed that the modification occurs post translationally and in a time-dependent manner. Membrane association studies using an SP-C precursor lacking the mature peptide indicated that the modification is of hydrophobic nature but not a thioester-linked fatty acid. PMID- 1591010 TI - Inhibition of pulmonary artery smooth muscle cell growth by hypoxanthine, xanthine, and uric acid. AB - We have previously reported that medium conditioned by hypoxic pulmonary artery endothelial cells (ECCM) contains a factor of small molecular weight that inhibits the growth of pulmonary artery smooth muscle cells (SMC). We postulated that this factor might be a breakdown product of ATP and, therefore, measured the levels of hypoxanthine/xanthine (HX/X) and uric acid (UA) in ECCM and cell lysates from endothelial cells (EC) exposed to hypoxia and normoxia. Although hypoxic and normoxic cell lysates contained no UA and an equal amount of HX/X (2.9 +/- 0.3 and 2.9 +/- 0.5 microM, respectively), there was a 5-fold increase in the amount of HX/X present in hypoxic compared with normoxic ECCM (3.4 +/- 0.3 versus 0.6 +/- 0.4 microM, respectively; P less than 0.001) but no difference in UA levels (5 +/- 2 versus 5 +/- 1 microM, respectively). In separate experiments, we examined the effects of exogenous HX, X, and UA (doses ranging from 0.1 to 100 microM) on the proliferation of pulmonary and aortic SMC and pulmonary artery EC. Our results indicate that HX, X, and UA inhibit the proliferation of SMC in a dose-dependent manner without causing injury to the cells. The proliferation of EC, on the other hand, was not affected by UA and was significantly inhibited by HX and X only at doses of 100 microM. In conclusion, we have found that significant amounts of HX/X accumulate in hypoxic ECCM and that HX, X, and UA inhibit the proliferation of SMC. The relevance of these findings to conditions where hypoxia prevails is discussed. PMID- 1591011 TI - Dog mastocytoma cells secrete a growth factor for fibroblasts. AB - It is suspected that mast cells play a part in the pathogenesis of fibrotic diseases, but the mediators that might be involved in induction of fibrosis have not been identified. We asked whether cultured dog mast cell lines produced growth factor(s) for fibroblasts. Three mastocytoma cell lines were found to secrete proliferative activity for human, hamster, and rabbit fibroblasts. Both mastocytoma cell-conditioned medium and cell extract served as competence factors for induction of DNA synthesis in confluent mouse Swiss 3T3 fibroblasts. The mitogenic activity in the conditioned medium was stable to heat, acid, and high concentrations of chaotropic agents or organic solvents but was decreased by treatment with proteases or reducing agents. The activity had an apparent molecular mass of 10 kD and did not bind to heparin. Activity eluted in a single peak from reverse-phase HPLC, and retention time differed from that of typical mesenchymal mitogens. We offer the hypothesis that mast cells produce growth factors for fibroblasts, possibly including a novel growth factor, and that this may contribute to pathologic fibrosis. PMID- 1591012 TI - Serotonin transport in reconstituted endothelial cell plasma membrane proteoliposomes: effect of hypoxia. AB - To determine whether changes in the lipid dynamics of the plasma membrane bilayer are responsible for hypoxic stimulation of serotonin (5-hydroxytryptamine [5-HT]) transport in pulmonary artery endothelial cells, we solubilized and isolated phospholipid and protein fractions from plasma membrane vesicles derived from endothelial cells exposed to 20% O2 (normoxia) or 0% O2 (hypoxia) for 24 h. Four different combinations of proteoliposomes were prepared by reconstituting (1) normoxic protein and normoxic phospholipid, (2) normoxic protein and hypoxic phospholipid, (3) hypoxic protein and normoxic phospholipid, and (4) hypoxic protein and hypoxic phospholipid. Fluorescence anisotropy of diphenylhexatriene (DPH), a measure of fluidity, and 5-HT transport were evaluated in each of the four groups of reconstituted proteoliposomes. 5-HT transport by the reconstituted proteoliposomes was saturable, linear with protein (5 to 25 micrograms) and time (15 to 60 s), and optimal with a phospholipid-to-protein ratio of 3:1. There were no significant differences in intravesicular volume, phospholipid-to-protein ratio, and size distribution among the four different groups of proteoliposomes. 5-HT transport was significantly higher and fluorescence anisotropy of DPH was significantly lower in proteoliposomes made from hypoxic phospholipids irrespective of the source of protein. Hypoxia also had a direct effect on the 5 HT transporter since uptake was increased slightly in proteoliposomes from group 3. These results indicate that changes in the plasma membrane phospholipids, and to a much lesser extent changes in the 5-HT transporter, are responsible for increases in the transmembrane transport of 5-HT by hypoxic endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591013 TI - Effects of interferons beta or gamma on neopterin biosynthesis and tryptophan degradation by human alveolar macrophages in vitro: synergy with lipopolysaccharide. AB - Interferons can induce neopterin biosynthesis and tryptophan degradation in monocytic cells. Indoleamine 2,3-dioxygenase (IDO), an inducible cellular enzyme, metabolizes tryptophan to N-formyl-L-kynurenine. Tryptophan degradation has been linked to interferon-mediated inhibition of replication by intracellular pathogens and inhibition of cancer cell proliferation. We evaluated the ability of the recombinant human interferons beta ser and gamma to stimulate neopterin production and tryptophan degradation in vitro by alveolar macrophages (AM) obtained from normal volunteers by bronchoalveolar lavage. Additionally, because other biologic response modifiers such as lipopolysaccharide (LPS) can also stimulate monocytic cells to produce increased amounts of neopterin and degrade tryptophan, we evaluated the effects of LPS on interferon-induced neopterin production and tryptophan degradation by AM. Both interferon-gamma (IFN-gamma) and interferon-beta (IFN-beta) induced neopterin production and tryptophan degradation by AM with corresponding inhibition of intracellular replication by Chlamydia psittaci in AM, but IFN-gamma was a more potent inducer of these responses than IFN-beta. LPS enhanced neopterin production and tryptophan degradation by interferon-exposed cells. This effect was particularly evident at lower concentrations of interferon, and LPS synergy was more pronounced with IFN beta than IFN-gamma. Concentrations of LPS that alone had no stimulatory effect on tryptophan degradation synergistically enhanced the induction of IDO activity by lower concentrations of interferon. These studies suggest that IFN-gamma stimulates human AM to produce neopterin and degrade tryptophan more potently than IFN-beta, and that low concentrations of LPS can synergistically enhance such effects of interferons on tissue macrophage metabolism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591014 TI - A factor secreted by a human pulmonary alveolar epithelial-like cell line blocks T-cell proliferation between G1 and S phase. AB - Because the pulmonary alveolar space is both the site of gas exchange for respiration and a portal of entry for foreign antigen, immunologic interactions within that space must be meticulously controlled. Alveolar epithelial cells are ideally situated to play a role in immune regulation within the alveolar space. We have used A549 cells, a cell line that is derived from a human alveolar cell carcinoma and that has been used as a model for alveolar type II epithelial cells, to examine the potential role of alveolar epithelial cells in local pulmonary immune regulation. Medium conditioned by confluent monolayers of A549 cells suppressed proliferation by human peripheral blood mononuclear cells (PBMC) stimulated with lectin, anti-CD3 antibodies, calcium ionophore and phorbol ester, or in a mixed leukocyte reaction. PBMC that had been incubated in and then removed from A549-conditioned medium went on to proliferate normally. Because the suppressive effect was abrogated by heating or acidification and was not blocked by neutralizing antibody to transforming growth factor-beta 1, this effect could not be attributed to transforming growth factor-beta. The factor mediating this effect has an approximate molecular weight of 70,000 D by gel filtration chromatography. Nonalveolar, pulmonary carcinoma cell lines did not exert this immunosuppressive influence nor did the alveolar epithelial cells inhibit proliferation by the transformed, Jurkat, T-cell line. Cell cycle analysis demonstrated that PBMC exposed to A549 cell-conditioned medium failed to enter S phase after mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591016 TI - Differential binding of IL-3 and GM-CSF to human monocytes. AB - Human monocytes respond to IL-3 and GM-CSF with a similar range of functional activities, and at similar cytokine concentrations. We have recently shown, however, that the rate of monocyte activation is greater in response to GM-CSF than to IL-3. In order to understand the basis of this phenomenon we investigated the interaction of IL-3 and GM-CSF with their surface receptors by means of kinetic binding experiments. 125I-GM-CSF showed very rapid association to monocytes at 37 degrees C, with a half-time of only 40 sec. The pattern of binding with this ligand was complex, with a decline in overall cell-associated radioactivity after 2 min of incubation. In contrast, 125I-IL-3 showed slower association, with a half-time at 37 degrees C of 2.5 min. The different rates of association correlated well with the different rates of cell activation induced by the two cytokines. On the other hand, rates of internalisation were similar for the two cytokines, with half-times of 14-15 min. Competition binding experiments performed under high affinity conditions showed that IL-3 and GM-CSF cross-competed for binding on the surface of monocytes. In contrast, under low affinity conditions IL-3 did not compete for 125I-GM-CSF binding while GM-CSF was a strong competitor of 125I-IL-3 binding. In quantitative inhibition experiments GM-CSF showed inhibitory effects on low affinity 125I-IL-3 binding at lower concentrations than those needed with unlabelled IL-3. It is suggested that current models of IL-3/GM-CSF receptor interactions need to be revised in order to accommodate the unique pattern of competition on human monocytes presented here. PMID- 1591015 TI - Mechanism of hydrogen peroxide-induced inhibition of sheep airway cilia. AB - To study the effect of the inflammatory mediator hydrogen peroxide (H2O2) on airway ciliary activity, we measured ciliary beat frequency (CBF) in cultured tracheal explants from sheep. Addition of H2O2 (10(-8) to 10(-4) M) produced a concentration-dependent mean (+/- SEM) decrease in CBF between 11.1 +/- 0.4% (P less than 0.01) and 100 +/- 0% (P less than 0.001); at each concentration, the maximal effect was reached by 20 to 25 min. Between 10(-8) and 10(-6) M H2O2, the decrease in CBF was reversible, lactate dehydrogenase (LDH) release was not significantly increased, and major morphologic lesions were not seen. At higher concentrations of H2O2, incomplete recovery of CBF (10(-5) M) or irreversible ciliostasis (10(-4) M) developed, and a significant increase in LDH and morphologic lesions were present. Catalase (2,000 U/ml) and H-7 (10(-5) M), a protein kinase inhibitor, abolished cilioinhibition produced by H2O2 at 10(-6) M and lower concentrations but not at 10(-5) M and higher concentrations. Phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, caused a dose dependent (10(-11) to 10(-5) M), reversible decrease in CBF; this effect was abolished by H-7. We suggest that at nonlethal concentrations, H2O2 inhibits the beat frequency of airway epithelial cilia reversibly, through the activation of second messengers, including protein kinase C. This mechanism might contribute to the previously demonstrated impairment of mucociliary clearance in airway inflammation. PMID- 1591017 TI - The role of basic fibroblast growth factor in skeletal muscle regeneration. AB - Muscle growth and regeneration is controlled by locally produced growth factors which activate satellite cells and stimulate their proliferation, differentiation and fusion to form mature myotubes. Basic fibroblast growth factor (bFGF) has been previously shown to promote proliferation and inhibit differentiation of myoblasts in vitro. In comparison, the in vivo role of this growth factor is less well documented. In the present investigation on the role of bFGF in muscle regeneration, bFGF mRNA levels were studied in two experimental systems: (1) primary cell cultures derived from rat skeletal muscles, and (2) an in vivo rat muscle injury model. bFGF mRNA was detected in myoblasts just prior to fusion and in myotubes of primary muscle cell cultures. In the non-injured muscle, bFGF mRNA transcripts were detected in myotubes but not satellite cells. In the in vivo muscle injury model bFGF mRNA was observed in myoblasts and in degenerating and regenerated myotubes. The significance of these experimental results in terms of the role played by bFGF in the myogenic program in vivo are discussed. PMID- 1591018 TI - Decreased level of transforming growth factor-beta in blood lymphocytes of patients with aplastic anemia. AB - Levels of transforming growth factor-beta (TGF-beta) activity in the conditioned medium of blood lymphocytes of twelve patients with aplastic anemia (AA), nine patients with myelodysplastic syndromes (MDS) and five normal volunteers were investigated. We were able to observe growth inhibitory activity on porcine endothelial cells only after acidification of the materials. The growth inhibitory activity is neutralized by anti-TGF-beta antibody. It indicates that TGF-beta exists as a latent form in the conditioned medium. On the basis of growth inhibition assay, the mean level of TGF-beta production of MDS patients was estimated to be 188 +/- 199 pg/1 x 10(7) cells and that of normal volunteers was 668 +/- 314 pg/1 x 10(7) cells. In contrast, the lymphocytes of almost all of the AA patients failed to produce detectable amounts of TGF-beta. No correlation between TGF-beta levels and peripheral blood parameters could be detected. Stimulation of lymphocytes by phytohemagglutinin is known to increase the production of TGF-beta. Induction of TGF-beta production was also observed in AA (45% of normal controls). Possible roles of the decreased production of TGF-beta in the pathogenesis of AA were discussed. PMID- 1591020 TI - [Parasagittal cerebral injury in perinatal asphyxia]. AB - It is suggested that parasagittal cerebral injury in the asphyxiated full term infant may be common. However, parasagittal cerebral injury is rarely diagnosed in the neonatal period. It is said that cranial ultrasonography and CT scan are not useful to identify this lesion. Recently, it is considered that some of the intellectual deficits and behavioral problems in children at school age may have their origin in perinatal parasagittal cerebral injury. We described a patient with parasagittal cerebral injury demonstrated by CT scan. Infants with neurological abnormalities which include weakness or abnormal muscular tone of proximal upper limbs suggest parasagittal cerebral injury. CT scan obtained between 1 and 3 weeks of life is considered to be useful for the diagnosis. Early diagnosis and follow-up of parasagittal cerebral injury may lead to the understanding of frequency, prognosis and pathogenesis and to its prevention. PMID- 1591019 TI - [Absence attacks with secondary bilateral synchrony]. AB - Three cases with petit mal absence attacks with secondary bilateral synchrony were presented. The interictal EEG showed unilateral focal epileptic discharges in the frontal area with normal background activity. The ictal EEG disclosed 3-Hz generalized symmetrical spike-wave patterns preceded by unilateral focal discharges, which were elicited by hyperventilation. None of the three cases had abnormal neurological findings or abnormal CT findings. All three cases had normal psychomotor development. One case had a history of febrile convulsions. The ictal manifestations were as follows; impairement of consciousness without any other signs in one case, with decreased posture tone in the second, and automatism in the third. The authors suggest that there can be petit mal absence with 3-Hz generalized spike-wave discharges induced by secondary bilateral synchrony. PMID- 1591022 TI - [Seizure-inducing factors in the patients with childhood epilepsy]. AB - We evaluated the seizure-inducing factors in 264 patients with childhood epilepsy. One hundred and thirty-six patients (51.5%) exhibited some kind of inducing factors. Non-specific inducing factors were commonly recognized, such as "febrile state" (29.2%), "fatigue after exercise" (15.2%), "sleep disturbance" (9.1%), "psychic stress" (8.3%) and "emotional change" (6.8%). Specific inducing factors, which related to reflex epilepsy, was recognized in only 7 patients. "Febrile state" was dominant in young children, but the other nonspecific inducing factors were dominant in adolescent. Incidences and kinds of inducing factors also related to the epileptic syndromes an seizure prognosis. The patients with symptomatic partial epilepsies (64.3%) and grand mal on awakening (85.7%) had significantly more inducing factors, and the patients with refractory seizures had a higher incidence and more variable kinds of inducing factors than the patients with well-controlled seizures. These results suggest that seizure inducing factors are recognized in children as well as in adults, and the clarification of inducing factors is important to the management of epilepsy, particularly of intractable epilepsy. PMID- 1591021 TI - [Dopamine beta-hydroxylase activity in cerebrospinal fluid of hydrocephalic patients]. AB - Dopamine beta-hydroxylase (DBH) activity in cerebrospinal fluid (CSF) was determined to evaluate the noradrenergic activity in the central nervous system of hydrocephalic patients in the acute phase. Seven patients with hydrocephalus resulting from various causes and 7 control children without neurological diseases were subjected to this study. DBH activity was measured by high performance liquid chromatography with electrochemical detection. DBH activity of control children, more than 5 years of age in our series, showed the similar activity of adult controls which was previously reported. Hydrocephalic patients revealed the higher DBH activity than controls (statistically significant, p less than 0.05). Sequential measurements of DBH activity in a case of herpes encephalitis revealed that its activity increased with the development of hydrocephalus and decreased after the treatment with repeated lumbar punctures. The present study suggests that the central noradrenergic activity is enhanced in the hydrocephalic patients in the acute phase. PMID- 1591023 TI - [1H and 31P magnetic resonance spectroscopy study of a case of phosphoglycerate kinase deficiency]. AB - Magnetic resonance spectroscopy (MRS) is a useful tool for detecting in vivo metabolic status and in vitro analysis of chemical metabolites. We performed MRS on a 15 year-old mentally retarded male patient with recurrent myoglobinuria due to phosphoglycerate kinase (PGK) deficiency. Muscle histochemistry was normal, although electron microscopy showed a significant increase in glycogen content. Biochemical analysis using muscle specimens revealed profound reduction of PGK activity to 4.4% of the control mean. In vivo MRS using 31P revealed a significant accumulation of sugar phosphates after ischemic forearm exercise, although no significant rise of inorganic phosphate was demonstrated during exercise. 1H MRS using the perchloric acid extracts of the blood taken at the ischemic forearm test, revealed no rise of venous lactate but a significant reduction of alanine levels. These data suggest that, unlike the patients with a glycogenolytic block, our patient with a distal glycolytic block shows a significant accumulation of sugar phosphates. The reason of the reduction of alanine levels was uncertain. A compensatory mechanism for energy supply to the muscle tissue was considered. PMID- 1591024 TI - [Neurological manifestations in hemorrhagic colitis associated with Escherichia coli O 157: H 7]. AB - From September through November 1990, an outbreak of hemorrhagic colitis associated with Escherichia coli O 157: H 7, occurred in a kindergarten in Saitama, Japan. Some of the patients suffered from neurological symptoms such as stupor, deep coma and/or convulsions in the acute stage, and/or action tremors, nystagmus, incontinence, phrenic nerve palsy in the later stage. Serum complements decreased more in the patients with neurological symptoms than in the patients without them. The verotoxin elaborated by E. coli O 157: H 7 was considered to cause the neurological symptoms, on the basis of their clinical courses and laboratory findings, especially the cerebrospinal fluid findings. PMID- 1591025 TI - [An infantile case of cerebral infarction associated with thrombocytosis]. AB - Cerebral infarction in children is often caused by intracranial vascular disorder, cardiac disease, head injury, or infection, and is rarely induced by blood disease. In this paper, we describe an infantile case of cerebral infarction associated with thrombocytosis. A female infant of eight months of age developed left hemiparesis after a slight head injury. Her CT and MRI demonstrated a cerebral infarction located from the right internal capsule to the right corona radiata. Laboratory findings revealed iron-deficiency anemia and thrombocytosis with a platelet count 107.5 x 10(4)/mm3. Although she had no disorder that had caused iron deficiency, serum Fe value of the patient was low with a count of 18 micrograms/dl. Her bone marrow was normal except for a slight increase in the number of megakaryocytes. One month later, her anemia was improved by means of oral iron replacement. However, her platelet count remained at more than 100 x 10(4)/mm3 as it had been before. Her condition of left-sided hemiparesis gradually improved by a program of rehabilitation, and did not recur after aspirin administration. Although the main cause of her thrombocytosis that led to a transient cerebrovascular accident is obscure, it is postulated that her iron deficiency anemia induced secondary thrombocytosis, or else the patient had essential thrombocytosis. PMID- 1591026 TI - [A case of tuberous sclerosis with congenital brain tumor; an immunohistochemical study]. AB - A case of tuberous sclerosis with congenital brain tumor was reported. The diagnosis was made on the basis of the pathological findings of subependymal giant cell astrocytoma, after surgery at the newborn period. After the neonatal period, the patient presented the classical triad of seizures, white spot of skin and mental retardation. The exact nature of tumor-forming giant cells remains controversial. We studied the nature of these cells using immunohistochemical method. GFAP, S-100 protein and NSE stains were all positive. This result suggested that the tumor cells had the features of both neurons and astrocytes. PMID- 1591027 TI - [Progressive cerebellar ataxia with diencephalic symptoms (Toyokura)--a case report]. AB - We reported a 16-year-old boy suffering from dwarfism, diabetes insipidus and progressive cerebellar ataxia. The disease entity here reported was originally reported by Toyokura et al. in 1967, under the title of "progressive cerebellar ataxia with diencephalic symptoms". Ten similar cases have been reported in literature so far, all of which were Japanese except for two sibling cases reported by Robinson et al. The topographic distribution of the lesion in this disorder, however, had been conjectured to be at spinocerebellar tract and diencephalon only on a clinical ground. By applying the modern techniques of neuroimaging, electrophysiological and endocrinological test in our patient, the authors were able to demonstrate the lesion of the disorder more precisely. CT and MRI of the head revealed degenerative changes in deeper structures of the bilateral cerebellar hemispheres. ABR abnormality suggested the presence of a wide lesion in the brain stem. Pituitary hormones (GH and ACTH) sufficiently responded to the loading of hypothalamic hormones such as growth hormone releasing factor and corticotropin releasing factor, in spite of poor responses of GH under the insulin stimulation or sleep. These clinical and laboratory findings suggested that the patient has a systemic degenerative disease which preferentially involves hypothalamus, brain stem and cerebellum. PMID- 1591029 TI - [The clinical and pathological features of siblings with infantile neuroaxonal dystrophy--early neurological, radiological, neuroelectrophysiological and neuropathological characteristics]. AB - The clinical and pathological features of siblings with infantile neuroaxonal dystrophy were reported. Early clinical symptoms were marked hypotonia in legs, mental regression and poor vision. Laboratory data were normal except for the mild elevation of GOT and LDH in serum and cerebrospinal fluid. MRI showed progressive atrophy of cerebellar vermis and brainstem. EEG showed a progressive increase in the amount and amplitude of the fast activities over the age of 3 years. Auditory brainstem response (ABR) showed progressive worsening with no response by 2 years and 6 months. Somatosensory evoked potentials (SEP) showed no cortical response by 4 years. Nerve conduction velocity (NCV) of both motor and sensory nerves was within normal limits. Pathologically, spheroid bodies were found in the axons of central and peripheral nerves, remarkably in brainstem and dorsal column. MRI, ABR and SEP findings were clinically useful, suggestive of the degeneration of brainstem. PMID- 1591028 TI - [Two cases of acute disseminated encephalomyelitis with lesions in the thalamus or basal ganglia on MRI]. AB - Lesions in the thalamus or basal ganglia have rarely been reported in acute disseminated encephalomyelitis (ADEM). We experienced 2 cases of ADEM, in which MRI showed lesions in the thalamus or basal ganglia. Case 1, a 4-year-old boy, had gait disturbance, hyperesthesia and hyperreflexia. MRI (T2 weighted image) showed multiple high intensity areas in the right frontal lobe, bilateral parietal lobes and bilateral thalami. Case 2, a 4-year-old girl, complained of gait disturbance following a febrile episode, and displayed hyperreflexia. Several days later, she had visual disturbance of the left eye. MRI (T2 weighted image) revealed multiple high intensity areas in the dentate nucleus of left cerebellum, left occipital lobe, bilateral caudate nuclei, and the anterior part of bilateral lenticular nuclei. In both cases, CT could not demonstrate these lesions. Both of them were treated with corticosteroid and recovered rapidly. They had no recurrence. MRI is useful in diagnosis and follow-up of ADEM and may reveal lesions other than cerebral or cerebellar white matters. PMID- 1591030 TI - [2',5'-oligoadenylate synthetase activity in cerebrospinal fluid of the children with aseptic meningitis]. PMID- 1591032 TI - [Intramuscular copper histidine treatment in Menkes disease]. PMID- 1591031 TI - [Cerebellar arteriovenous malformation associated with facial hemangioma and arteriovenous fistula of the scalp]. PMID- 1591033 TI - [Cerebellar hypoperfusion in epileptic children]. PMID- 1591034 TI - [Human type II collagen induced autoimmune inner ear lesions in guinea pigs]. AB - Guinea pigs were immunized with human type I, type II or type III collagen. Inner ear lesions were induced in some guinea pigs by immunizing them with human type II collagen. Histopathologic changes included endolymphatic hydrops, organ of Corti lesions and endolymphatic duct contained a large number of inflammatory cells. These histologic changes resembled those observed in patient with Meniere's disease. We didn't discover any inner ear lesions in guinea pigs by immunizing them with human type I and type III collagen, although their serum antibody titers were high and antibody presented in perilymph. Immunohistochemical study showed the presence of type II collagen in the cochlea tissues--spiral ligament, basilar membrane, tectorial membrane, spiral limb and Rosenthal's canal. We didn't discover type I and type III collagen in these area. PMID- 1591035 TI - [A preliminary study on the mechanism of immune injury of Meniere's disease--type V collagen play the role of antigen]. AB - In the serum of patients with Meniere's disease, we have found significantly increased circular immune complex with solid C1q ELISA method (P less than 0.01), significantly increased anti-human placental type-V collagen antibody with ELISA method (P less than 0.01) and significantly increased immunoglobulin G and immunoglobulin M with single directional radiation immunodiffusion (P less than 0.01) when compare to control group. We have also induced spontaneous nystagmus by inoculating guinea pigs with this collagen. As a result, in the autoimmune lesion of Meniere's disease, type-V collagen may have an important role as antigen. PMID- 1591036 TI - [Evaluation of compound action potential tuning curves from normal guinea pig cochleas]. AB - Eighteen ears of normal guinea pigs were examined by means of compound action potential tuning curve (AP-TC) with different measure parameters. AP-TC was measured at pure-tone of various frequencies using simultaneous masking procedure by the electrodes on the round window. AP was evoked by filter click (2, 3, 4, 5, 6, 10 kHz) with an intensity 10, 30 and 50 dB above threshold. Masker level producing 30% reduction in AP amplitude was used. The results showed that AP-TC was more sharply as test frequency was elevated. It is corresponded well with the published results. No differences in tuning (i.e., the form of the curves and Q10 dB values) and thresholds were found between two different times for the same animal. In addition, the Q10 dB values of AP-TC were gradually reduced along with the elevate of the test stimuli intensity from 10 to 50 dB above threshold. PMID- 1591037 TI - [Scanning electron microscopic study on newborn middle ear mucosa]. AB - Scanning electron microscopic studies were made on the mucosa of newborn middle ear. The results were: 1. The epithelial surface was found to contain four types of cell: the ciliated cell, the nonciliated cell without secretory granules (SG), the nonciliated cell with secretory granules (SG) and the flat cell. 2. The ciliated cell population appeared in the following order (from dense to sparse): eustachian tube, hypotympanum, antetympanum, epitympanum, promontory and post tympanum. 3. The density of nonciliated cell without SG population was gradually increasing from anterior to posterior part of middle ear. 4. The population of nonciliated cell with SG was fewer and they were always found near the ciliated cells. 5. The flat cells were only seen on the flaccid part of tympanic membrane. This paper suggests that the ciliary system is basically mature and the development of mucus secreting members still is not perfect in newborn middle ear mucosa. PMID- 1591039 TI - [Central low frequency hearing loss]. AB - Sixteen central hearing loss cases were studied. The typical clinical findings were bilateral low frequency loss, low speech discrimination score, abnormal ABR, predominant-SP, normal EOAE, and normal 40Hz AERP. The possible etiological factor and site of the lesion were discussed. PMID- 1591038 TI - [Experimental study on the mechanism of free radical in blast trauma induced hearing loss]. AB - The MDA content in the cochlear tissue and ABR hearing threshold were measured at different times after the explosion of the guinea pigs. Results showed that there were two high peak values. The MDA increases at one hour after explosion; at 3 and 6 days it was significantly increased (first peak); at 8 days it reduced to normal level; at 12 days it again remarkably increased (second peak). It was in accordance with ABR hearing threshold changes. This suggests that increasing oxygen free radical reaction may be one of the causes of damage in blast trauma induced hearing loss. PMID- 1591040 TI - [Selective facial neurectomy for hemifacial spasm]. AB - Twenty-six patients were treated for hemifacial spasm by selective facial neurectomy. The symptoms of hemifacial spasm can be relieved by performing extracranial selective facial neurectomy with preservation of the temporal and cervical ramus. The facial nerve branches have been identified by selective electrical stimulation over the nerve, which evokes responses from the corresponding facial muscles. Selective facial neurectomy were completed when stimulation of the nerve produces minimal movement in the orbicularis oculi muscle while normal contractions appear in the frontal region and lip portion. The results of surgery 2 years postoperatively indicated that the complete disappearance of hemifacial spasm was achieved in 65.6 percent of the patients. A slight relief was achieved in 15.5 percent of the patients. Unsatisfactory results were obtained in 11.5 percent. No spasm recurred in 7.5 percent of patients, but paralysis of frontal muscle persisted. PMID- 1591041 TI - [Changes in the nasal mucosal microvascular with allergic rhinitis]. AB - The nasal mucosal microvascular of 37 patients with allergic rhinitis had been studied by nasal mucosal microcirculation microscope. It was found that the nasal mucosal microvascular diameter was wider after the nasal challenge test than before, but both after and before the nasal challenge test, the nasal mucosal microvascular diameter in patients with allergic rhinitis was narrower than in normal persons. The number of the microvascular in patients was also less than that in normal persons. The results indicate that the nasal mucosal microvascular with allergic rhinitis are characterized by dilated capacitance vessels and exchange vessels and constricted resistance vessels after nasal allergen challenge. PMID- 1591042 TI - [Cochlear compound nerve action-potential tuning curve]. PMID- 1591043 TI - [Experimental autoimmune lesions of the inner ear]. AB - This paper presents the autoimmune lesions of the inner ear by using isologous inner ear antigen (IEAg) on the guinea pigs. The purposes of this study were to determine whether the inner ear is an immune response organ and what is the sequelae of the immune processes both on physiological and morphological changes in the inner ear. Animals were systemically sensitized with IEAg in complete Freund's adjuvant and boothed with IEAg in incomplete Freund's adjuvant three times in every 3-4 weeks and then allowed to survive 4-6 weeks. For the ABR measurement, 8 of 28 ears (28.6%) in the experimental group showed threshold enhancement greater than or equal to 10dB before the animal sacrifice and the mean threshold shift of the ABR 8 weeks post immunization and before sacrifice revealed significant difference. Histological specimens were processed for both light and electron microscopic study. In the LM study, it showed endolymphatic hydrops, local thickening of the Reissener's membrane, and spiral ganglion cells lost. In the SEM, disturbance and loss of the cilia of the outer hair cells of the cochlea and the type I and II sensory cells in the crista ampularis can be seen. Also, some otoconia showed numerous malformation. PMID- 1591044 TI - Abnormal oestrogen receptor in clinical breast cancer. PMID- 1591045 TI - Tobacco or health: a WHO programme. AB - Tobacco is currently estimated to be responsible for 3 million deaths per year. The WHO, as a leader in international health, had to react to this situation to protect the health of the world's population against this new man-made epidemic. The traditional functions of the organisation and its structure have enabled it to create a global programme on tobacco or health; new approaches in health promotion will make the activities of this programme easier to follow by all countries and more cost-efficient for its member states. This article endeavours to summarise how the different constitutional mandates of WHO have given rise in the Tobacco or Health programme to (1) activities in support of health promotion advocacy and public information; (2) validation and dissemination of information; and (3) development of national tobacco control programmes. Furthermore, the WHO governing bodies are offering a forum for debate on these matters and buttressing national policies through international support and carefully steering WHO's Tobacco or Health programme in the face of almost permanent new scientific and political happenings, to keep its activities within the confines of WHO's role and the goals of the Tobacco or Health programme. The organisation has endeavoured to move the tobacco or health agenda towards the problems of developing countries who can still avoid the looming tobacco epidemic. Finally, a global strategy of health protection and promotion priority is given to women and children. PMID- 1591046 TI - Follow-up in patients treated for head and neck cancer: how frequent, how thorough and for how long? PMID- 1591047 TI - Mutations in the ras protooncogenes are rare events in renal cell cancer. AB - Mutations in codon 12, 13 or 61 of one of the three ras genes, Ha-ras, Ki-ras, and N-ras, convert these genes into active oncogenes. To determine the role mutated ras genes play in the carcinogenesis of renal cell carcinoma, we analysed tumour DNA and unaffected renal tissue derived from 55 patients. The polymerase chain reaction technique was used to amplify DNA fragments containing Ki-, Ha-, and N-ras codons 12, 13, and 61. The amplified fragments were then probed on slot blots with labeled mutation-specific oligomers. A single Ki-ras mutation (codon 12, gly- greater than val) was detected in a patient with a pT2N2M1 tumour. We concluded that ras oncogene mutations do not play an important role in the initiation of renal cell carcinoma. PMID- 1591049 TI - Phenotypic and functional analysis of tumour-infiltrating lymphocytes from patients with melanoma and other metastatic cancers. AB - Thirty tumour specimens, among which were 17 melanomas, were cultured with recombinant interleukin-2 (IL-2) in order to produce tumour-infiltrating lymphocytes (TIL). In the melanomas, three categories of TIL were characterised. The first, containing mostly CD3+ and CD8+ cells, lysed only autologous tumour cells; the second, containing mostly CD3+ and CD4+ cells, lysed both autologous tumour cells and allogeneic cells lines; the third, with mixed phenotype although cytotoxic for K562 targets, did not kill melanoma cells. The optimal conditions for a good development of TIL were established: we found that the lymph node or cutaneous origin of the tumour was unimportant, a 2 h enzymatic treatment was optimum and that TIL grew well in AIM V serum free medium. Therefore the easiness and the reproducibility of the TIL cultures from melanoma tumour samples allows the rapid development of therapeutic trials in metastatic melanoma. PMID- 1591048 TI - Mitogenic effects of epidermal growth factor and transforming growth factor-alpha on EGF-receptor positive human ovarian carcinoma cell lines. AB - The role of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) in the growth modulation of three human ovarian adenocarcinoma cell lines, PEO1, PEO4 and PEO14, has been examined by measuring responses of the cells growing in monolayer culture to exogenous addition of the growth factors. The presence of EGF receptors in the cell lines has been confirmed by ligand binding and immunocytochemical staining using a monoclonal antibody directed against the EGF receptor. The growth of all three cell lines was stimulated by both EGF and TGF-alpha. Dose-response effects were noted with the greatest growth stimulation occurring at concentrations between 0.1 and 10 nmol/l. The stimulatory effects of EGF and TGF-alpha were accompanied by changes in the cell cycle distribution as detected by flow cytometric analysis. It is concluded that EGF and TGF-alpha are important growth regulators in these EGF-receptor positive ovarian cancer cells. PMID- 1591050 TI - Flow cytometric analysis of tumour-draining lymph nodes in breast cancer patients. AB - The phenotype and activation status of lymphocytes from the peripheral blood and axillary lymph nodes of 40 patients with breast cancer were analysed using flow cytometry and compared with lymphocytes from the blood and lymph nodes of 7 control subjects. There was little difference in the overall proportions of T and B lymphocytes but there was a much larger population of B cells bearing surface IgG and a greater number of CD4+ helper T cells, particularly in the regional nodes, in the breast cancer patients. Many more T cells in the cancer patients were found to be carrying the HLA DR and Tac antigens. The axillary lymph nodes were the major site of B cells and CD4+ T cells whilst the primary tumour was the source of the CD8+ suppressor/cytotoxic T cells. Any immune response appeared to be largely loco-regional and may therefore destroyed by conventional surgery or radiotherapy. PMID- 1591051 TI - Potentials of cell kinetics in the management of patients with ovarian cancers. AB - The relevance of 3H-thymidine labeling index (3H-dt LI) on clinical outcome was evaluated on 85 patients with advanced ovarian cancers treated with carboplatin or cisplatin alone (39 cases) or cisplatin in association with doxorubicin and/or cyclophosphamide (46 cases). 3H-dT LI of the primary tumour was significantly related to the 3-year probability of survival in patients treated by monochemotherapy (low LI, 63%; high LI, 21%; P = 0.013) but not in those treated with polychemotherapy. Analysis of the relation between cell kinetics and clinical outcome as a function of treatment showed that in patients with rapidly proliferating tumours the 3-year survival was significantly higher following polychemotherapy than monochemotherapy (51 vs. 21%; P = 0.04). In patients with slowly proliferating tumours no significant difference in survival was observed following the two types of treatment for the overall series, whereas in patients not achieving a complete response survival was significantly higher following monochemotherapy than polychemotherapy (61 vs. 9%; P = 0.008). PMID- 1591052 TI - Metastatic ovarian or colonic cancer: a clinical challenge. AB - Clinical problems arise when histology is unable to differentiate between an ovarian carcinoma infiltrating into the rectosigmoid region and a colonic cancer with ovarian metastases. To evaluate the discriminative value of immunohistochemistry we studied four groups: (A) ovarian carcinoma (n = 21), (B) ovarian carcinoma with sigmoid stenosis (n = 18), (C) colonic carcinoma (n = 20) and (D) a group in which the differential diagnosis was a problem (n = 19). Paraffin sections stained with a panel of monoclonal antibodies revealed specific patterns: in group A and B a negative Parlam-4 and positive OC-125; in group C the opposite; in group D the 'colonic' pattern in 15 cases, and the 'ovarian' pattern in only 2. The clinical diagnosis in group D during follow-up was ovarian carcinoma in 7, colonic carcinoma in 8, double tumour in 1 and still unknown in 3. This was based on high levels of serum tumour markers such as carcinoembryonic antigen (n = 5) and CA-125 (n = 4), laparotomy (n = 4), autopsy (n = 1), barium enema and/or endoscopy (n = 5). The response to chemotherapy in group D was extremely poor. PMID- 1591053 TI - Pilot study of a rapid etoposide-cisplatin regimen in paediatric soft tissue sarcomas. AB - 10 patients with refractory or relapsed soft tissue sarcoma were treated with weekly etoposide (150 mg/m2 on days 1, 2 and 3) and cisplatin (60 mg/m2 on day 2). Toxicity was mainly myelosuppression which resulted in deviation from planned weekly chemotherapy scheduling. With this rapid dose-delivery schedule the tolerated median dose intensities were 161 mg/m2 per week for etoposide and 49 mg/m2 per week for cisplatin. In 9 evaluable patients there were 7 responses, 2 complete and 5 partial, giving a response rate of 78% (confidence interval 51 100%). The combination of etoposide and cisplatin in this schedule produced a higher response rate than reported with previous schedules and is worthy of further evaluation. PMID- 1591054 TI - An endocrine and pharmacokinetic study of four oral doses of formestane in postmenopausal breast cancer patients. AB - 43 postmenopausal breast cancer patients were treated orally with the aromatase inhibitor formestane (4-hydroxyandrostenedione) at daily doses of 62.5, 125, 250 or 500 mg for 4 weeks followed by 250 mg daily for a further 4 weeks. For some patients, 62.5 mg did not suppress serum oestradiol levels maximally. The doses of 250 and 500 mg did not differ in their effectiveness. Oestrone levels were suppressed by all doses of formestane but no consistent changes of aldosterone, cortisol or 17-hydroxyprogesterone occurred. Serum levels of sex hormone binding globulin fell by about 15% during treatment with 250 mg formestane reflecting its minor androgenic activity. The maximum concentration and area under the curve of serum formestane levels after the first dose varied in an approximately linear manner with dose. It is concluded that formestane is an effective, specific suppressant of oestradiol levels via the oral route requiring no more than 250 mg to be given daily. PMID- 1591055 TI - Head activator as a potential serum marker for brain tumour analysis. AB - Some human brain tumours, especially those derived from neuroectodermal or neural crest cells, contain elevated levels of head activator (HA). Such tumours release HA into the general circulation resulting in up to 1000-fold higher HA serum concentrations. The diagnostic value for brain tumour analysis was studied by measuring HA serum levels before and after human brain tumour surgery. It was found that complete removal of the tumour resulted in normal HA serum levels postsurgically. Incomplete resection was accompanied by a marked decrease, but not a return to normal HA levels. Surgery as such did not influence HA serum levels, since no change was observed pre- and postsurgically in patients with normal HA serum levels. This confirms the potential usefulness of HA as a serum marker to monitor brain tumour progression, successful tumour removal and relapse. PMID- 1591056 TI - Long-term prognostic significance of thymidine labelling index in primary breast cancer. AB - Tumour growth rates, as measured by incorporation of tritiated thymidine, have been reported as being of prognostic importance in breast cancer. We have measured the thymidine labelling index (TLI) of 185 early breast cancers, followed-up for a minimum of 8 years. Above median TLI was associated with higher tumour grade, but not with other prognostic factors. TLI was not predictive of survival in either univariate or multivariate analysis. The inter- and intra observer reproducibilities of TLI measurements were poor, which may be a factor limiting its usefulness as a prognostic indicator in breast cancer. PMID- 1591057 TI - The value of follow-up in patients treated for squamous cell carcinoma of the head and neck. AB - Clinical findings, treatment and results have been recorded prospectively in 661 patients with carcinoma of the head and neck. With an average follow-up of 3 years 7813 follow-up consultations revealed 220 recurrences. The overall "recurrence pick-up rate" and subsequent "cure rate" was 1:36 and 1:113 consultations, respectively. Laryngeal carcinomas treated with radiotherapy and oral carcinomas receiving radiotherapy and limited resections showed recurrence "cure-rates" of 1:89 and 1:110, respectively. For other tumour sites the average "cure-rate" was 1:238. Only 39% of the recurrences were detected through physical examination. Follow-up consultations revealed 9.1% of second primaries. More time should be spent on training patients to recognise symptoms and signs of recurrence. Routine follow-up is rarely indicated beyond the third year after completion of treatment, or in patients for whom we have little to offer in terms of curative treatment. PMID- 1591058 TI - Progressive loss of antiemetic efficacy during subsequent courses of chemotherapy. AB - The maintenance of the antiemetic efficacy of a combined protocol (intravenous methylprednisolone, oral thiethylperazine and oral amitriptyline) during six consecutive courses of adjuvant FAC chemotherapy (5-fluorouracil, doxorubicin, cyclophosphamide) was analysed in 107 female breast cancer patients who completed the six planned courses of treatment. A continuous decrease in complete (no vomiting episodes) and major protection rate (0-2 vomiting episodes) was evident during chemotherapy. Complete protection rate decreased from 62.6% in the first course to 48.6% in the sixth (P less than 0.05, chi 2 test). The respective figures for major protection rate were 76.6% and 58% (P less than 0.01, chi 2 test). These data, together with other from the literature, should be taken into consideration when reviewing the overall results of current antiemetic trials, which usually only mention the results obtained in the first course of chemotherapy. PMID- 1591059 TI - Interferon alpha 2a and vindesine in the treatment of advanced malignant melanoma. AB - 21 patients with advanced malignant melanoma were treated with interferon alpha 2a at 9MU daily with vindesine every 21 days. No patient had received previous chemotherapy. The overall response rate was 24% with a median survival time of 33 months in 18 patients. The four complete remissions were maintained for 20, 18, 15 and 11 months, while the single partial remission continues at 18 months after the start of treatment. Side-effects were generally mild or moderate and did not lead to cessation of therapy. This combination provides an active outpatient regimen for advanced melanoma and produces durable remissions. PMID- 1591061 TI - A phase II study of sequential recombinant interleukin-2 followed by dacarbazine in metastatic melanoma. AB - 16 patients with disseminated malignant melanoma (1 with primary ocular melanoma) entered a multicentre phase II study of recombinant interleukin-2, (rIL-2) given by continuous intravenous infusion on days 1-5 at 18 x 10(6) IU/m2 per day, followed by dacarbazine 850 mg/m2 on day 8. After a 2 week rest, a second course was given. In the absence of disease progression, monthly maintenance cycles were given for up to four cycles. 16 patients received one cycle, 14 received two and 6 patients three or more. All 16 patients are evaluable for toxicity and 15 for response. 2 patients responded (13%). 1 patient with lung and pleural metastases achieved partial remission after two cycles and went off treatment after six cycles. 3 months later a complete response was noted lasting 396+ days. A second patient with lung metastases had a partial response lasting 153 days. 3 patients (20%) had stable disease. Mean rebound lymphocytosis (24-48 h after the end of rIL-2 therapy), cell count 4.9 x 10(9)/l (2.6-8.8 x 10(9)/l) was within the expected limits. Other toxicity was as expected. Thus sequential treatment with rIL-2 and dacarbazine is feasible but synergy did not occur. PMID- 1591060 TI - A phase II study of metastatic melanoma treated with a combination of interferon alfa 2b, dacarbazine and nimustine. AB - 52 patients with metastatic melanoma have been treated with a combination of recombinant interferon-alfa-2b, dacarbazine and nimustine. The objective response rate was 23% with 9 complete responses (CR) and 3 partial responses (PR). The mean duration of the response was 18+ months for CR (6-31+ months) and 7 months for PR patients (4-10 months). The mean survivals were 24+ months (8-38 months) and 7 months (4-12 months), respectively. The mean duration of the response for patients with stable disease was 10+ months (2-48+ months) and the mean survival 17+ months (3-48+ months), while the patients with progressive disease died within 12 months (mean 4 months). The best responding sites were the lymph node, the lung and the subcutaneous metastases. Myelosuppression was the main adverse effect of the therapy. WHO grade 3-4 toxicity was seen in 27 patients leading to delay and reduced dosage of therapy; in 4 patients treatment was discontinued, 8 patients had no side effects. Combination therapy with interferon and dacarbazine and nimustine for metastatic melanoma offers no advantage over interferon and dacarbazine. PMID- 1591062 TI - Sequential administration of dacarbazine and fotemustine in patients with disseminated malignant melanoma--an effective combination with unexpected toxicity. AB - Resistance to alkylating agents is partly due to the presence of the DNA repair enzyme, termed O6 alkyltransferase (O6AT). Preclinical evidence of the transient restoration of sensitivity of cells resistant to nitrosoureas by pretreatment with a methylating agent, whose role is to deplete cells of O6AT activity and clinical evidence of such a depletion in patients lymphocytes, led us to test the sequential administration of dacarbazine 3 h prior to fotemustine, a chloroethylnitrosourea derivative. 24 patients with measurable advanced melanoma entered the trial and are evaluable. Toxicity was mainly haematological with early neutropenia and/or thrombocytopenia. Clinical activity (33%) was impressive especially on lung metastases with high complete response rate for that site (7/14). Unfortunately, the occurrence of a rapidly fatal pulmonary toxicity precludes further use of the regimen before a plausible explanation for this unexpected toxicity is obtained. Indeed, similar cases have been reported in other trials using the sequential schedule while no lung toxicity was reported in single agent or alternated administrations. Preclinical studies are ongoing to test the hypothesis of a glutathione depletion and the possibility of a rescue treatment. PMID- 1591063 TI - Parotid gland function during and following radiotherapy of malignancies in the head and neck. A consecutive study of salivary flow and patient discomfort. AB - Radiotherapy of tumours in the head and neck region usually involves the salivary glands in the treatment volume with ensuing dryness and discomfort. In the present study, a prospective evaluation of the same patients were performed before, during radiotherapy and 6, 12 and 18 months after the end of treatment. Three different groups were outlined, one receiving doses not exceeding 45 Gy, another 47-52 Gy and a third group treated with doses over 64 Gy. All but one of the patients receiving doses less than 52 Gy showed a recovery of secretion beginning after 2 months with a continuous improvement of the salivary flow up to 18 months. Doses exceeding 64 Gy caused irreversibly depressed parotid function in the vast majority of glands. The subjective experience of discomfort with dry mouth was not at all correlated to the initial flow rate. Treatment with unilateral technique and doses below 52 Gy caused just no or slight dryness and 3 out of 4 patients with bilateral involvement of the glands displayed problem with subjective dryness even after 18 months. Doses over 64 Gy with one gland involved had only slight dryness, however, patients with both glands affected showed severe problems with dryness. It has to be emphasised that there were relatively large interindividual differences with respect to salivary flow and discomfort of dryness. It is obvious that these patients need a careful dose planning and a close follow up with co-operation between radiotherapeutists and dentists. PMID- 1591064 TI - Phase I trial of the anthrapyrazole CI-941: prospective evaluation of a pharmacokinetically guided dose-escalation. AB - The development of new drugs in early clinical trials is currently based upon the results of preclinical antitumour and toxicity studies in animals. More recently, the use of preclinical pharmacokinetic information in mice has been proposed to also provide information that might expedite early clinical trials and more specifically phase I studies. The anthrapyrazole CI-941 was one of three chosen for phase I anticancer drug development. In addition, because of the predictability of the preclinical dose limiting toxicity and linear CI-941 pharmacokinetics in mice; a pharmacokinetically guided dose escalation scheme was attempted during the phase I trial, but had to be abandoned. 44 patients were entered who received 95 courses of treatment using a bolus injection every 21 days. The dose range was 5-55 mg/m2. The dose limiting toxicity was leucopenia and other toxicities, which included nausea and vomiting, mucositis, diarrhoea, alopecia and skin discolouration were either mild or manageable. Pharmacokinetic studies were performed with 27 courses. There were wide interpatient variations in the dose-AUC relationship (r = 0.7496) that hampered application of the proposed pharmacokinetically guided dose escalation scheme as planned. No complete or partial responses were observed. The recommended phase II dose using this schedule is 50 mg/m2. PMID- 1591065 TI - Phase I study of subcutaneously-administered bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor. AB - A phase I study was initiated to test the effect of bacterially-synthesised recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). 15 patients with advanced cancers were entered into the study and 14 were evaluable. Patients were administered a single subcutaneous injection (3.0-300 micrograms/m2) of rhGM-CSF. Starting at a concentration of 100 micrograms/m2, an approximate 2-fold increase in leucocyte count was noted 24 h after the injection. By 48 h the counts had returned to baseline. The 300 micrograms/m2 concentration also induced an approximate 2-fold increase. The leucocytosis was associated with a predominant increase in circulating neutrophils and bands. An increase in monocytes was also noted, but peak levels were recorded 48-72 h after the injection. At both the 100 micrograms/m2 and the 300 micrograms/m2 doses, significant levels of circulating rhGM-CSF were detected. The levels measured in the plasma of patients receiving 300 micrograms/m2 were over 10-fold greater than those measured at 100 micrograms/m2. There was no detectable antibody formation against the rhGM-CSF in any of the study patients. The drug was exceptionally well-tolerated. This study shows that rhGM-CSF can be safely administered by subcutaneous administration and a single injection is capable of inducing a leucocytosis with increased circulating neutrophils, bands, and monocytes when doses are used which result in significant levels of circulating rhGM-CSF. PMID- 1591067 TI - A phase I-II study with intraperitoneal cisplatin plus systemic etoposide in patients with minimal residual ovarian cancer. AB - In patients with residual ovarian cancer after standard platinum-based induction, dose intensification was achieved by intraperitoneal administration of cisplatin 90 mg/m2 with intravenous Na thiosulphate and increasing dosages of etoposide. 40 patients entered the study, 4 on 200 mg/m2, 6 on 400 mg/m2, 22 on 600 mg/m2 and 8 on 800 mg/m2 etoposide. The optimal dose for etoposide was 600 mg/m2. 29 patients on the two highest dose steps were evaluable for response. 14 patients reached a complete remission, which was surgically confirmed in 6. All these patients initially had tumour residuals smaller than 1 cm. 3 patients had a partial response, 4 had stable disease and 8 progressed. At a maximal follow-up of 2 years (median 12 months), median time to progression was 12 months and median overall survival was 14 months. Of the 14 patients with complete remission, 2 relapsed at 9 and 11 months. Apart from a rash, in 4 of 22 patients at 600 mg/m2 and in 5 of 8 at 800 mg/m2 etoposide, the main toxicity was leukopenia grade 3-4 in 58% of cycles on 600 and in 76% at 800 mg/m2 etoposide. Leukopenic fever, however, occurred only three times; thrombocytopenia was rare. Cycles had to be delayed sporadically and the etoposide dose was reduced in 9% of all cycles at 600 and in 11% at 800 mg/m2. Intraperitoneal instillation of cisplatin gave no peritoneal symptoms. Intraperitoneal cisplatin with intravenous etoposide was tolerable and effective for patients with small tumour residuals after induction for stage III ovarian cancer. PMID- 1591066 TI - Phase II study of platinum and mitoxantrone in metastatic prostate cancer: a Southwest Oncology Group Study. AB - 44 eligible patients with measurable or evaluable metastatic prostate cancer were treated with monthly cycles of cisplatin and mitoxantrone. Good-risk patients received cisplatin 60 mg/m2 intravenously and mitoxantrone 10 mg/m2 intravenously every 4 weeks. The dose in poor-risk patients (elderly or white blood cell count less than 4000/microliters, 4 x 10(9)/l, or extensive prior radiation) was reduced to 8 mg/m2. Toxicity was manageable and consisted primarily of myelosuppression. There were no complete responses and the partial response rate was only 12%. Median progression-free survival was 2.7 months for measurable and 4.1 months for evaluable disease patients. Median survivals were 4.9 and 8.7 months, respectively. This combination has minimal activity in hormone refractory metastatic prostate cancer. PMID- 1591068 TI - Control of chemotherapy-induced diarrhoea with octreotide in patients receiving 5 fluorouracil. AB - Chemotherapy treatment with combination of 5-fluorouracil and leucovorin or interferon alpha determined an incidence of severe diarrhoea of 10 and 20%, respectively. Up to date no treatment for this condition has been defined. 21 patients affected by advanced colorectal cancer and 6 patients affected by advanced pancreatic cancer received octreotide as treatment for severe diarrhoea following chemotherapy with 5-fluorouracil/leucovorin (Machover's regimen) or 5 fluorouracil/interferon (Wadler's regimen) combination. Octreotide was administered by subcutaneous injection of 50 micrograms twice daily on the first day and 100 micrograms twice daily on the second and third day. 26 patients had total cessation of diarrhoea: 4 patients within the first day, 6 within the second day and 16 within the third day. 1 patient had no change and after the last administration of octreotide he was treated with loperamide and intravenous hydration. Side effects have been mild. In summary octreotide seems to be an effective agent in the management of chemotherapy related diarrhoea. PMID- 1591069 TI - Phase II trial of pirarubicin in epidermoid carcinoma of the head and neck. PMID- 1591070 TI - Does the breast cancer dollar make sense? AB - The past decade has witnessed a transformation of breast cancer management. Innovative developments such as widespread mammographic screening, breast conserving approaches to primary disease and adjuvant systemic therapy have improved the quality of breast cancer care in the community. These and other therapeutic developments have been accompanied by substantial increases in consumption of health care resources. With the exception of adjuvant systemic therapy for node-positive disease, the evidence that such increases have been associated with commensurate improvements in disease outcome is weak. Indefinite continuation of this trend may prove incompatible with socioeconomic realities. PMID- 1591071 TI - Second malignancies in thyroid cancer patients: a population-based survey of 3658 cases from Norway. AB - In a population-based survey of 3658 thyroid cancer patients diagnosed in Norway during 1955-85, a total of 200 cases of second malignancies were observed (30,414 person-years, mean follow-up 8.4 years). Male patients had a significantly increased incidence of urogenital cancer [standardised incidence ratio (SIR) = 1.96, 95% confidence interval (CI) 1.4-2.7], including cancer of the testis (SIR = 11.8, 95% CI 3.2-30.1) and urinary bladder (SIR = 3.0, 95% CI 1.5-5.2). The occurrence of malignant melanoma was also increased among males (SIR = 4.2, 95% CI 1.4-9.7). This apparent association with urogenital cancers among males at the present time cannot be explained, although increased surveillance as well as specific aetiological factors should be considered. PMID- 1591072 TI - Dietary factors in lung cancer prognosis. AB - A hypothesis-generating analysis of the role of diet on survival was conducted among a sample of 463 men and 212 women with histologically-confirmed lung cancer. Interview information was obtained from two population-based case-control studies of lung cancer conducted on the Island of Oahu, Hawaii, between 1979 and 1985. The interview consisted of a quantitative dietary history to assess the usual intake of foods 1 year prior to diagnosis, a complete tobacco history, and other demographic and lifestyle information. Records from the Hawaii Tumor Registry were reviewed for data on stage, histology, and follow-up status of these patients. A food group analysis showed a significant reduction in the risk of death with increasing consumption of all vegetables combined among women (P for trend = 0.03), but not among men. The covariate-adjusted median survival times for women from the highest to the lowest quartiles of vegetable intake were 33, 21, 15, and 18 months, respectively. The results also suggested an association of fruit intake and survival among women (P for trend = 0.02), although a similar effect was not found among men. Increased consumption of certain foods, such as tomatoes and oranges among men, and broccoli and, perhaps, tomatoes among women, appeared to improve survival. This exploratory analysis provides mixed indications that certain components of vegetables and fruits may prolong survival in lung cancer patients. PMID- 1591073 TI - Breast cancer, blindness and melatonin. AB - The hypothesis is advanced that blindness from an early age may lead to a reduced risk of breast cancer through altered patterns of melatonin secretion by the pineal gland. The available experimental evidence in animals and in vitro is consistent with this hypothesis. The hypothesis can be tested in humans by a simple observational study in which the breast cancer risk in blind women is compared with that of all women. The effect of age at onset, duration and degree of blindness could also be assessed, after adjustment for known risk factors for breast cancer. Melatonin might prove to be a natural oncostatic agent of practical value in cancer prevention. PMID- 1591074 TI - Is DNA flow cytometry a useful investigation in breast cancer? PMID- 1591075 TI - PET scanning in oncology. PMID- 1591076 TI - Monoclonal antibodies in the treatment of central nervous system malignancies. PMID- 1591077 TI - Trends of cancer mortality in Europe, 1955-1989: II, Respiratory tract, bone, connective and soft tissue sarcomas, and skin. PMID- 1591078 TI - Consensus on the management of melanoma of the skin in The Netherlands. Dutch Melanoma Working Party. AB - In 1990, the Dutch Melanoma Working Party, in cooperation with the National Organization for Quality Assurance in Hospitals, organised the second consensus conference on the management of melanoma of the skin. The following guidelines were approved: The margin of a therapeutical excision should be 1 cm for melanomas not thicker than 1.0 mm, 2 cm for a thickness of 1.1-2.0 mm, 3 cm for a thickness of 2.1-3.0 mm. No consensus was reached for tumours thicker than 3.0 mm. The conclusion of the histopathological report should state the histological type of melanoma, the thickness, the level of invasion, the presence of ulceration, regression, microsatellitosis and completeness of removal. In melanomas between 1.5 mm and 4 mm, elective lymph node dissection may be considered, but its value has not been proven. Clinically suspicious regional lymph nodes require a therapeutical lymph node dissection, solitary lymph node removal is inappropriate. Prophylactic (adjuvant) regional perfusion in primary melanoma should only be performed in the context of a clinical trial. Regional perfusion is the treatment of choice for satellitosis and/or in-transit metastases of the extremities without evidence of distant metastases. If radiotherapy is indicated, high fractionation doses are required. There is no standard therapy for distant metastases. Routine check radiographs and laboratory studies are unnecessary during the follow-up period. The follow-up period is normally 10 years. PMID- 1591079 TI - Quality control of EORTC case report forms--wider implications for trial management. PMID- 1591080 TI - High-dose folinic acid, 5-fluorouracil bolus and continuous infusion in metastatic colorectal cancer: a 3-day/3-week schedule. Group d'Etude et de Recherche sur les Cancers de l'Ovaire et Digestifs (GERCOD) PMID- 1591081 TI - Intra-arterial cisplatin in advanced squamous cell carcinoma of the bladder. PMID- 1591082 TI - Treatment of recurrent gynaecologic malignancies with a new camptothecin derivative. PMID- 1591083 TI - Meningeal carcinomatosis in urothelial cancer. PMID- 1591084 TI - Lack of effect of tumour infiltrating lymphocytes in patients with metastatic melanoma who failed to respond to interleukin 2. PMID- 1591085 TI - Breast conserving therapy: workshop report. PMID- 1591086 TI - Breast cancer: adjuvant treatment. PMID- 1591087 TI - Breast cancer diagnosis and prognosis in women following augmentation with silicone gel-filled prostheses. AB - 62 healthy women were studied mammographically before and after augmentation mammoplasty. Postaugmentation mammograms were done using both the implant compression and implant displacement technique. The amount of visualisable tissue was measured in all films before and after augmentation. We concluded: State-of the-art film-screen mammography is extremely difficult to obtain in most patients augmented with silicone-gel-filled prostheses. On average, there is a decrease in measurable visualised breast tissue after augmentation mammoplasty with silicone gel-filled prostheses. The area of mammographically measurable tissue is no different whether smooth or textured implants are used. Textured implants are less likely to form an early capsular contracture and are therefore preferred. However, the cancer-causing potential of polyurethane in humans is currently unknown. Anterior breast tissue is generally seen better with displacement mammography; posterior breast tissue with compression mammography. Better films are generally obtained when the implant is in the subpectoral position rather than subglandular. The more severe the capsular contracture, the poorer the mammogram. In addition 42 previously augmented patients developed breast carcinomas an average of 8.4 years after augmentation with silicone-gel-filled implants; 95% had palpable lesions (only 60% of which could be seen on mammography), 90% had infiltrating carcinomas, 45% had metastases to axillary nodes, and 7 patients have recurred, 5 of whom have died. We concluded: Augmented women who develop breast cancer are similar, in terms of tumour size and nodal positivity, to non-augmented breast cancer patients who present with palpable masses. When compared with non-augmented women whose breast cancers are found with screening mammography, augmented patients with breast cancer present with a higher percentage of invasive lesions and involved axillary lymph nodes, resulting in a poorer prognosis. The 40% false negative rate for mammography in this series is unduly high and alarming. Augmentation mammoplasty with silicone gel-filled implants should be discouraged in women with a high risk of developing breast cancer. PMID- 1591088 TI - A preliminary report on the usefulness of monoclonal antibodies to CA 15-3 and MCA in the detection of micrometastases in axillary lymph nodes draining primary breast carcinoma. AB - The most critical factor affecting survival in patients with breast carcinoma is axillary nodal involvement. Monoclonal antibodies raised against specific human mammary tumour associated antigens may increase detection of micrometastases. This preliminary report examines two of these antigens; CA15-3 antigen and mucin like carcinoma associated antigen (MCA) in the detection of such deposits. Specimens from 39 stage 1 (node negative) breast carcinoma patients were assessed. Two further 'negative' sections were stained with antisera to CA15-3 and MCA antigens. Micrometastases were detected in 5 patients and in each, MCA and CA15-3 identified the same micrometastases. 3 of these patients had disease progression compared with 3/34 of the remaining patients. The use of monoclonal antibodies to CA15-3 and MCA significantly (P less than 0.05) increases detection rates of micrometastases and this is associated with significantly worse disease free survival rates (P less than 0.001). PMID- 1591089 TI - Factors influencing the risk of local recurrence in the breast. AB - This paper reviews what is currently known regarding possible factors influencing the risk of local failure in the breast after conservative surgery and radiation therapy for clinical stage I and II breast cancer. The best established features correlating with increased risk are young age at time of primary therapy, and the presence of an extensive intraductal component within the primary tumour. The interactions of tumour- and treatment-related factors is complex, but adequacy of surgical excision, quality of radiation therapy technique, and use of systemic therapy all appear to contribute to risk reduction. PMID- 1591090 TI - Systemic treatment for locally advanced breast cancer: what we still need to learn after a decade of multimodality clinical trials. AB - Multimodality therapy of locally advanced breast cancer with initial chemo (hormono)-therapy followed by locoregional treatment has become increasingly popular during the past decade. A paucity of large randomised clinical trials leaves the following unanswered questions: does systemic treatment impact on long term control of distant metastases? What is the best treatment sequence? The most effective drug combination? The optimum treatment duration? Future prospects in the treatment of locally advanced breast cancer include the use of haematopoietic growth factors to increase the dose-intensity of neoadjuvant chemotherapy, the investigation of autologous bone marrow transplantation with high dose chemotherapy on a larger scale, the development of new approaches designed at interrupting the "autocrine loop" of breast cancer local growth factors and the introduction of diphosphonates in the adjuvant systemic therapy. PMID- 1591091 TI - Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node positive, oestrogen-receptor positive breast cancer patients. An update at 7 years of the 1st GROCTA (Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group) trial. AB - 504 evaluable node positive oestrogen receptor (ER) positive breast cancer patients were randomly allocated to receive either 5 years tamoxifen treatment or chemotherapy [six courses of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 4 courses of epirubicin] or a combination of both treatments. At a median follow-up of 5 years tamoxifen appeared to be more effective than chemotherapy, the difference being highly significant in postmenopausal women. The addition of chemotherapy to tamoxifen was not able to significantly improve the results achieved by tamoxifen alone, irrespective of menopausal status. Trends were similar even after stratification for the number of involved nodes. The protective effect of tamoxifen in terms of reduction of the odds of death increased with time and no rebound phenomena on recurrence or death has occurred so far after the completion of tamoxifen treatment. Overall, the prognostic value of number of involved nodes and of progesterone receptor (PgR) status was confirmed by multivariate analysis. However, the predictive value of PgR was lost in patients receiving tamoxifen alone. Similarly, the degree of ER positivity was not predictive of the response to tamoxifen. Tamoxifen treatment should still be regarded as the gold standard for postmenopausal ER positive patients. In younger women the antioestrogen proved to be safe and at least as effective as chemotherapy. However, the analysis of the annual risks suggests that the concurrent or the sequential use of chemotherapy and tamoxifen might represent a more appropriate treatment for this patient subset, particularly for those with four or more involved nodes. Different cut-offs of ER and PgR assays from those we have arbitrarily employed in the present analysis should probably be used to select more properly the patients who can benefit from endocrine therapy. PMID- 1591092 TI - DNA flow cytometry and response to preoperative chemotherapy for primary breast cancer. AB - Between October 1988 and June 1990, 22 patients with locally advanced, inoperable breast cancer entered a pilot study of four cycles of anthracycline based cytotoxic chemotherapy followed by surgery and tamoxifen. Fine needle aspirate samples of tumour were obtained for DNA flow cytometry before treatment and during the first cycle of chemotherapy. 21 patients are eligible for assessment of response and toxicity. Chemotherapy was well tolerated with greater than WHO grade 2 vomiting or stomatitis in 4 patients. Granulocytopenia less than 10(9)/l was noted in 16/21 patients but there were no episodes of neutropenic sepsis. There were 7 complete responses (CR) and 11 partial responses (PR), giving an overall response rate to chemotherapy (CR+PR) of 18/21 (86%). Responses were observed more commonly in patients who had aneuploid tumours (P = 0.06) and in patients whose tumours had a high S-phase fraction (P = 0.1). Tumours which responded to chemotherapy (CR or PR) had a significantly higher median SPF compared with tumours which did not regress (P less than 0.05). There was no consistent pattern of change in SPF values during the first cycle of chemotherapy, either for patients who responded to treatment or for those whose tumours did not regress. This combination therapy is well tolerated with a high response rate. The results of this pilot study support the recent suggestion that tumours with rapidly proliferating, aneuploid populations of cells exhibit the best short-term response to chemotherapy. PMID- 1591093 TI - Tamoxifen protects against steroid-induced bone loss. AB - As part of a clinical trial of adjuvant endocrine treatment in postmenopausal women with operable breast cancer serial bone density measurements have been performed by dual photon absorptiometry. Tamoxifen alone was given to 26 women, and 20 received additional prednisolone. By 24 months after entry there was no significant difference between mean bone density of the two groups, nor any significant change from baseline levels. There was a mean gain of 0.46% in the tamoxifen group and 1.95% in those given additional prednisolone. Thus the predicted steroid-induced bone loss was inhibited by tamoxifen. This may be of more general use in prevention of osteoporosis in patients requiring long-term steroid treatment. PMID- 1591094 TI - Dose intensity of chemotherapy with cyclophosphamide, methotrexate and 5 fluorouracil in the elderly with advanced breast cancer. AB - Toxicity and results of two different dose levels of chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in older (greater than 70 years) patients with advanced breast cancer were evaluated in a prospective (non randomised) study. During the first three courses of chemotherapy dose reduction for haematological toxicity was necessary in all of 10 and 8 of 13 patients treated with an intended dose of 100% and 75% of standard dose CMF, respectively. The median percentages of CMF, administered during the first three courses were about 75% in both groups of patients corresponding with a median dose intensity of 72% (range 49-87%) and 64% (range 36-78%) for patients of the 100% and 75% dose group, respectively. In 34 younger postmenopausal women (mean age 57 years) treated in our institution for advanced breast cancer the median percentages of CMF in the second and third course were 86% and 84%, respectively with a median dose intensity during the three courses of 82%. Dose reductions of CMF and bone marrow toxicity, though interdependent, were statistically significantly correlated with the endogenous creatinine clearance, but not with age. 1 patient died during severe leukopenia and thrombocytopenia. Non-haematological side effects were most pronounced in the 100% group. Results of therapy in both groups of patients were about equal and compared well with those of CMF therapy in general. It is advised that the dose of CMF in patients above 70 years should not exceed 75% of standard dose. Further dose reduction of methotrexate in case of severe renal failure is required. PMID- 1591095 TI - Parathyroid hormone related protein and skeletal morbidity in breast cancer. AB - The presence of parathyroid hormone related protein (PTHRP) in human breast cancers has been assessed by immunohistochemistry using a polyclonal antiserum specific for the mid-region sequence 37-67 in an immunoperoxidase technique. The primary tumours from 155 normocalcaemic, consecutive women with early breast cancer who had been followed up for a minimum of 5 years were assessed. Dewaxed paraffin sections of formalin fixed tissue was used throughout. Positive PTHRP staining was detected in 56% of the cancers and was unrelated to standard prognostic factors, recurrence or survival. However, PTHRP positivity was related to the development of bone metastases (P less than or equal to 0.03) and hypercalcaemic episodes. PTHRP is implicated as the humoral factor responsible for hypercalcaemia associated with breast cancer and tumour positivity may be a useful predictor of which women will develop bone metastases. PMID- 1591096 TI - Epidermal growth factor receptors in human breast cancer: a plea for standardisation of assay methodology. AB - In a prospective study 200 primary human breast cancer specimens were analysed for epidermal growth factor receptor (EGFR) content by means of a multiple point ligand binding assay, proposed by the EORTC Receptor Study Group to be the standard EGFR assay. In 54% of the tumours the presence of saturable high affinity binding sites for epidermal growth factor could be demonstrated. The median EGFR level was 34 fmol/mg of membrane protein, the median Kd 0.50 nmd. Univariate analysis of the EGFR data stratified according to patient age, menopausal status, tumour size, axillary lymph node status, histological tumour type, tumour differentiation grade or the tumours' steroid hormone receptor status showed EGFR to be positively associated with younger age (P = 0.03), tumour dedifferentiation (P = 0.04) and steroid hormone receptor negativity (P less than 0.001). No association between EGFR and menopausal status, tumour size, axillary lymphnode status or histological tumour type could be demonstrated. PMID- 1591097 TI - DNA ploidy and other results of DNA flow cytometry as prognostic factors in operable breast cancer: 10 year results of a randomised study. AB - We evaluated breast cancer specimens from 241 patients of a controlled clinical trial by means of DNA flow cytometry. We report the correlations between DNA index (DNI) and fraction of cells in S-phase (SPF) and other prognostic parameters. Both univariately and in a Cox model, the predictive power of these factors is evaluated after a follow-up of more than 10 years. There are strong correlations between DNI and SPF (P = 0.0001) and between flow cytometry parameters and clinical and histopathological factors such as axillary lymph node involvement, tumour size and histological grade. In univariate analysis DNI fails to provide prognostic information, whereas SPF turns out to be able to differentiate between patients at high and low risk for relapse and death (P = 0.002). In the multivariate Cox model, too, SPF is an important prognostic parameter with respect to patient survival (relative risk: +86%), only surpassed by nodal involvement. DNI, however, turns out to be an independent predictor of relapse free survival and distant recurrence free survival. By combination of DNI and SPF, patients can be divided into three prognostic subgroups. We conclude that data from DNA flow cytometry can be of great importance for the decision on the level of aggressiveness of adjuvant therapy for an individual patient and therefore may help to avoid overtreatment and toxicity. PMID- 1591098 TI - [Stereotactic radiosurgery using the gamma knife]. PMID- 1591099 TI - [A newly designed salt bridge cap-type, a variable, and non-invasive EEG lead electrode and the analytical power spectrum]. AB - A newly devised, variable EEG cap-style electrode that has an electrical salt bridge with 2% agarose gel and 5% NaCl solution was developed. The number of electrodes can be increased as required. The weight of 15 electrodes is about 100g. The electrode is simple, fast and in a one-touch form for measuring the EEG. An EEG using this electrode system was recorded in a healthy man in a sitting position on a chair, at rest, and with eyes closed. The power spectrum showed different patterns for the power at different concentrations of aqueous solution in the matrix of the salt bridge. The power changed to a pattern of J type with 20% NaCl solution, to a pattern of U-type with 5% NaCl solution, and to a pattern of L-type with 0.9% NaCl solution, respectively. The matrix of the salt bridge that has a concentration higher than 0.9% NaCl, is a hypertonic solution for the isotonic body liquid. One person felt pain in half of the part of the experiment when a 20% NaCl hypertonic solution was applied to the scalp, so a 20% NaCl solution of the salt bridge was used in experiments concerning osmosis. When a salt bridge of 5% NaCl solution was used, the same results of the wave measurement was obtained 10 times. It was a value close to the expected measurement so it has a high probability of being correct. At this time the power spectrum shows a U-type pattern consistently. PMID- 1591100 TI - [Effect of anticonvulsants upon experimental limbic seizure status and regional cerebral blood flow in the hippocampus]. AB - Continuous monitoring of regional cerebral blood flow (rCBF) of the hippocampus was made during limbic seizure status in cats by means of a heat clearance method with a calibration method by an electrolytic hydrogen clearance method. A stereotaxic operation was made under Nembutal anesthesia. Local anesthetics were applied to the painful area. Femoral artery and vein were cannulated and served for arterial blood pressure monitoring and drug injection, respectively. Tracheostomy was made and ventilated artificially. A double cannula was inserted to the amygdala and fixed to the skull with a dental cement. Electrodes for heat clearance method, electrolytic hydrogen clearance method and EEG recording were inserted to the dorsal hippocampus. Limbic seizure status was induced by kainic acid microinjection (2 ug) into amygdala via implanted cannula. Baseline rCBF was measured in each cats. Continuous monitoring of rCBF was made before and after intravenous administration of anticonvulsants such as zonisamide (ZNS), valproic acid (VPA), diazepam (DZP), phenobarbital (PB) and phenitoin (PHT). Physiological saline (PHS) was injected for controls. Injection of DZP resulted in strong seizure suppression with decrease of arterial blood pressure and hippocampal rCBF. Intravenous PB demonstrated analogous action with DZP with a mild anticonvulsant effect. Intravenous ZNS or VPA resulted in inhibition of seizure propagation from limbic system to cortex. However, these drugs augmented rCBF of the hippocampus more than 2 hours after administration. PHT and PHS demonstrated no anticonvulsant effect nor rCBF change in the present study. PMID- 1591101 TI - [MR imaging of the spinal cord--with special emphasis on the factors influencing spinal cord measurement]. AB - On MR images the spinal cord is seen differently in size depending on imaging parameters and displaying window; consequently the findings may be interpreted erroneously as swelling or atrophy of the spinal cord. The purpose of this paper was to evaluate factors influencing spinal cord size on images and to determine the optimal condition estimating the size of the spinal cord. At first we selected 4 cases suspected of cervical spinal disorders which had been examined by both MRI and myelography with tomography. Sagittal diameter of the spinal cord was measured on a film and it was significantly different of those three. That is, the measurement value was greater on T1 weighted image (T1WI) and smaller on T2 weighted image (T2WI) than myelo-tomography. To evaluate the effect of imaging parameters, image reconstruction and image displaying window quantitatively, studied were the cadaveric cervical spinal cord and gelatin phantom tube with a diameter of 13 mm and 9 mm placed in a saline-filled plastic tube. The measurement value was significantly greater on T1WI and smaller on T2WI than true size of the objects. Numbers of phase encoding (128 and 256) significantly affected the measurement value, both on T1WI and T2WI, as well. Ringing artifact of high or low signal was observed at the boundary area of the objects and saline (so-called truncation artifact). However, when the window-level of displaying image was raised stepwisely the measurement value was proportionally decreased and it reached to real value when the level was adjusted at the mean MR signal intensity of the object and saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591102 TI - [Cytoskeletal proteins abnormalities in olivopontocerebellar atrophy]. AB - A highly sensitive silver technique for glial cytoplasmic inclusions in olivopontocerebellar atrophy (OPCA) was applied to 15 subjects with neurodegenerative disorders including 4 patients with OPCA, 4 patients with Joseph disease and with 3 normal control subjects, and the argyrophilic structures in the OPCA cases were immunocytochemically examined. As a result, the argyrophilic structures were found in the OPCA cases and Alzheimer cases. The argyrophilic structures included the white matter oligodendroglia, and neurons, astroglia and oligodendroglia in the putamen, pontine nucleus and inferior olivary nucleus. The pontocerebellar tracts and the surrounding white matter of the inferior olivary nucleus contained a small number of argyrophilic nerve fibers with a hollow structure, which were interpreted as myelin. Immunocytochemistry demonstrated that the oligodendroglia in the white matter had immunoreactivities to an paired helical filament (PHF), microtubule associated protein 5 (MAP5), tau and ubiquitin antiserum, and the astroglia in the white matters had an immunoreactivity to a MAP5 antiserum. In the putamen, pontine nucleus and inferior olivary nucleus, in addition to the immunoreactivities observed in the oligodendroglia, the neurons were immunoreactive for PHF, MAP5, tau and ubiquitin antisera, and the astroglia had the same immunoreactivities as the neurons except for being tau negative in the putamen. The nerve fibers in the pontocerebellar tract and inferior olivary nucleus capsule were strongly positive for myelin basic protein and negative for PHF antiserum. These findings indicate that the Gallyas positive argyrophilia in the OPCA subjects is closely associated with PHF or tau. PMID- 1591103 TI - [MELAS associated with diabetes mellitus and point mutation in mitochondrial DNA]. AB - Point mutation of mitochondrial DNA has been described in the blood from a MELAS patient. The 39-year-old patient developed progressive dementia, stroke-like episodes, heart conduction defect (Lown-Ganong-Levin syndrome) and cortical blindness. CT scan revealed brain atrophy and low density areas in the bilateral occipital lobes. Laboratory tests showed hyperglycemia and lactic acidosis. Muscle biopsy showed ragged red fibers on Gomori trichrome staining. He was clinically diagnosed as having MELAS and insulin-dependent diabetes mellitus. Onset of diabetes mellitus and MELAS was almost same. Family history showed his mother's brother and sisters had also insulin-dependent diabetes mellitus. We amplified the leucine (UUR) tRNA gene from the patient's blood with polymerase chain reaction (PCR) and analysed it by restriction enzyme analysis and sequencing. Genetic analysis showed A-to-G substitution at the nucleotide position 3243 in the leucine (UUR) tRNA gene. This substitution made a new restriction site Apa I. Mutant DNA coexisted with wild type DNA (heteroplasmy). It is shown that in some types of mitochondrial encephalomyopathies, especially patients of Kearns-Sayre syndrome (KSS), diabetes mellitus is often complicated. And in KSS patients insulin receptor in normal, but insulin secretion from beta cells of pancreas is decreased. In MELAS patients, however, has diabetes mellitus been reported to be rarely complicated and relationship between MELAS and diabetes mellitus is not done. As far as we know, two cases, including ours, with genetically diagnosed MELAS have been reported to have diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591104 TI - [Anatomical analysis of the sources of somatosensory evoked fields (SEFs) using 3D-MRI]. AB - We have recorded short latency somatosensory evoked magnetic fields (SEFs) to left median nerve stimulation in three healthy subjects. The locations of the deduced dipole sources were projected onto the 3-Dimensional magnetic resonance imaging (3D-MRI) of the individual subjects providing an anatomical localization. We found that the deduced sources were located at the primary sensorimotor hand area on the posterior surface of the central sulcus, at an average depth of 26mm (11mm) from the scalp (brain surface). This technique that combined MEG with 3D MRI was able to precisely determine source locations and analyze the relationships between dipole sources and brain structures. By using this technique, we can confirm functional anatomy of the brain noninvasively, and obtain much useful information preoperatively and during operation. PMID- 1591105 TI - [A case of extracerebral cavernous hemangioma in the middle fossa]. AB - Authors reported an autopsy case of extracerebral cavernous hemangioma in the middle fossa and discussed the effect of irradiation therapy on it. A 72-year-old woman was admitted due to progressive deterioration of consciousness and the right hemiparesis. CT scan revealed a slightly high density mass, which was markedly heterogeneously enhanced with contrast media, in the left middle cranial fossa. Angiogram with prolonged injection demonstrated a faint tumor stain. Craniectomy and partial temporal lobectomy for decompression were performed, but the tumor could not be removed due to uncontrollable hemorrhage. Her level of consciousness further deteriorated, and in addition heart failure developed. And finally she became vegetative in spite of effective irradiation therapy of 46Gy. CT scan taken three months and seven years after the irradiation showed marked regression of the tumor. After the vegetative state for 8 years, the patient died of acute pancreatitis, and autopsy was performed. The cavernous hemangioma with markedly proliferated interstitial connective tissue and thrombosed vessels was verified by microscopical examination. Although the treatment was not successful in this patient, we confirmed that irradiation is useful in the management of the extra-axial cavernous hemangioma in the middle fossa as a pre- or postoperative adjunct therapy. PMID- 1591106 TI - [Hereditary dentatorubropallidoluysian atrophy--clinical variants in a family and degeneration of cerebral white matter in a proband]. AB - We describe a family with hereditary dentatorubropallidoluysian atrophy (DRPLA). 4 patients through 3 successive generations showed a wide clinical variety. The female proband with onset in the elderly developed choreiform involuntary movement, dementia, hyperreflexia and, at the progressive stage, mild ataxia. However she had never displayed epilepsy and myoclonus. The 2 sons showed dementia, choreoathetoid movement and ataxia. The grandson developed typical signs and symptoms of progressive myoclonus epilepsy. The brain CT in the proband showed severe cerebellar and brain stem atrophy, moderate cerebral cortical atrophy and diffuse low density lesions in the deep cerebral white matter. Her neuropathological examination revealed the atrophy and gliosis of cerebral and cerebellar white matter concomitant with both dentatorubral and pallidoluysian system degeneration. The present study indicates that hereditary DRPLA can include multiple clinical variants even in the same family and the degeneration of cerebral and cerebellar white matter besides dentatorubral and pallidoluysian system. PMID- 1591107 TI - Implementing universal precautions against infection. AB - As noted recently in the Journal, a small number of dentists, according to their own reports, do not always wear protective clothing such as gloves and a mask in treating their patients. The profession's recommendations for infection control have thus not been observed. The following describes some of the influences on the decisions taken by dentists to take or neglect these measures. PMID- 1591108 TI - 'Do you treat HIV positive patients?'. PMID- 1591109 TI - 'Do you treat HIV positive patients?'. PMID- 1591110 TI - 'Do you treat HIV positive patients?'. PMID- 1591111 TI - Metal-ceramic bridges from commercial dental laboratories. PMID- 1591112 TI - 'An urgent remedy needed'. PMID- 1591113 TI - 'Dental aid in the Himalayas'. PMID- 1591114 TI - 'The cementation of porcelain jacket crowns with adhesive resins'. PMID- 1591115 TI - Saliva: its secretion, composition and functions. AB - The secretions of the major and minor salivary glands, together with the gingival crevicular fluid, constitute the oral fluid or whole saliva which provides the chemical milieu of the teeth and oral soft tissues. The crucial role of saliva in the maintenance of dental health is demonstrated by the morbidity associated with loss of salivary gland function. In this article, the physiology of the secretory process, the reflex control of whole saliva flow rate, the composition of the fluid, the factors affecting its composition, and the functions of the organic and inorganic components are described. Finally, the clinical aspects of salivary gland dysfunction are briefly discussed. PMID- 1591116 TI - Prosthetic assessment in the treatment of denture hyperplasia. AB - The removal of denture-induced trauma is important in the treatment of denture hyperplasia and in the prevention of its redevelopment in susceptible patients. A simple approach to the assessment of dentures is described, which highlights potentially damaging areas of the borders and the fitting surface. PMID- 1591117 TI - The adhesive amalgam--fact or fiction? AB - Forty molar and premolar teeth had non-retentive cavities prepared and restored with amalgam using (1) copal varnish (control), (2) a pin, (3) Amalgambond or (4) Panavia-Ex. The forces and energy required to dislodge the restorations were recorded and compared, and the mode of failure noted for each group. Although the pinned restorations required significantly higher loads to dislodge them, the mode of failure and energy required to dislodge the restorations in the Amalgambond and Panavia-Ex groups indicated that these types of restorations had significant advantages over pinned restorations, particularly where the pulp might be compromised. The film thickness of the retentive systems in these two groups, however, indicated a substantial operator or technique sensitivity. PMID- 1591118 TI - A new oral surgery teaching model. AB - An anatomical model for teaching the practical aspects of routine oral surgery in a clinical or laboratory environment, is described. Replaceable sections allow the model to be rapidly re-used so that successive students may practise procedures such as incisions, flap reflection, bone removal, tooth removal, apicectomy and suturing. Keeping the cost per procedure to a minimum was considered to be of fundamental importance and this has been achieved through the use of 'factory produced' replacement parts. PMID- 1591119 TI - MR imaging, flow and motion. AB - The present work is intended as a nonmathematical review of the role of flow and motion in nuclear magnetic resonance (MR) imaging. A historical review of MR flow measurement techniques is given, followed by a short overview of flow models in vitro and in vivo. The theory behind the influence of motion on the modulus and phase MR signal information is discussed and effects such as washin/washout, flow induced signal void, phase offset, and phase dispersion are defined. A simple approach to the concept of MR angiography is given, and methods for quantitative flow measurements such as the phase mapping technique, are surveyed. Aspects of the measurement of diffusion and microcirculation are given, and finally, an overview of the role of MR flow imaging in present and future clinical application is given. PMID- 1591120 TI - MR imaging of chronic alcoholism. AB - We evaluated the brain lesions of patients with chronic alcoholism (n = 34) in comparison with age- and sex-matched controls (n = 40) by MR imaging. T1-weighted sagittal and axial images and T2-weighted axial images were obtained with a 0.5 T superconducting MR unit. Various brain measurements were then performed, and the presence of regions of abnormal signal intensity was also compared between the two groups. The brain measurements revealed significant cerebral atrophy (characterized by lateral and 3rd ventricular dilatation, and widening of the interhemispheric fissure) as well as significant cerebellar atrophy (represented by 4th ventricular dilatation) in the alcoholic group. These changes were more prominent in patients in their fifties and sixties than in those aged in the thirties and forties. Focal hypointense lesions were observed in 20.6% of the alcoholics and in 5% of the controls (p less than 0.01), while focal hyperintense lesions were observed in 61.8% of the alcoholics and in 20% of the controls (p less than 0.001). The severity of these MR findings correlated well with the age of the patients. These observations suggest that alcohol is an important promoter of brain aging. PMID- 1591121 TI - MR imaging of intradural extramedullary tumors. AB - Thirty-one consecutive intradural extramedullary spinal tumors examined with MR at 0.3 T were reviewed. In 13 of the patients myelography had been performed. There were 11 patients with meningeoma, 14 with neuroma, one ependymoma, 3 metastases, and 2 lipomas. All tumors were surgically removed and verified by histology. The intradural extramedullary location of the tumors was accurately assessed by MR imaging in all patients and by myelography in 10 of 13. The MR diagnoses were in accordance with the histologic findings in 74% of cases. Compression of the spinal cord or cauda equina with widening of the subarachnoid space above and below the mass or outward displacement of epidural fat was characteristic of the intradural extramedullary tumors. The signal intensity of meningeoma as well as of neuroma was slightly lower or equal to that of the cord on T1-weighted images, and equal to or higher than cord signal on T2-weighted images. Neuroma had a lower signal intensity on T1-weighted images and a higher signal intensity on T2-weighted images than meningeoma. Meningeoma appeared more homogeneous than neuroma and had a broad base towards the dura. PMID- 1591122 TI - MR imaging with histopathological correlation in vertebral metastases of breast cancer. AB - In 5 patients with advanced breast cancer and spinal metastases MR imaging of the spine was performed before and/or after death. T1-, proton density-, and T2 weighted and "phase contrast" images were obtained in the sagittal plane. Autopsies included histopathologic examination of whole sagittal sections of the vertebral body. The relative signal intensities on the different MR sequences of various tissues identified histologically were evaluated. "Phase contrast" images combined with T1-weighted images were highly sensitive in detecting metastases. All metastatic tumours over 3 mm in size were found with MR imaging. Vertebrae containing connective tissue and reactive bone marrow had an MR appearance similar to that of metastases even though no metastases were found histopathologically. PMID- 1591123 TI - Contrast medium injected into juvenile bone cysts to analyze interior morphology and guide intracavity corticosteroid treatment. AB - In connection with treating juvenile bone cysts with intracavital corticosteroid injections, the interior cyst anatomy was analyzed at cystography in 13 children aged 4 to 15 years. Only 4 children had a true unicameral cyst; the others had 2 or more cysts or had compartments with free or restricted communication to the main cyst. Cysts and compartments which had not been reached by steroids may continue to grow. Optimum treatment may therefore require injections at different sites guided by cystography. Neither conventional criteria of cyst activity nor repeated bone scintigraphy 3 months after treatment could predict whether the treatment would lead to final healing. PMID- 1591124 TI - Combined CT-guided biopsy and cytology in diagnosis of bony lesions. AB - The results of 44 trephine (OD 1.4-4 mm) biopsies and 39 fine needle (0.7-0.9 mm) aspirations of skeletal, mainly vertebral, lesions performed under CT-guidance in 54 patients were evaluated. The fine needle sample was aspirated through the trephine as a complementary procedure in 29 patients and a fine needle aspiration only was performed in 10 patients. Trephine biopsy only was performed in 15 patients. Sufficient material for histologic and cytologic analyses was obtained in 93% (41/44) and 97% (38/39) and a correct benign or malignant diagnosis was obtained in 84% (37/44) and 90% (35/39), respectively. Among the combined examinations the fine needle aspiration alone was diagnostic in 2 cases while the trephine specimen alone provided diagnostic material in 2 cases. In 24 cases both the cytologic and histologic samples were adequate for diagnostic purposes. In one case both methods gave false-negative results. The combined use of cytologic and histologic samples in CT-guided bone biopsies increased diagnostic accuracy. The aorta was perforated once with a 1.4-mm needle but without sequelae. CT guided bone biopsy was found to be a safe, reliable and cost-efficient method. PMID- 1591125 TI - Precision of hyaline cartilage thickness measurements. AB - Measurement of cartilage thickness in vivo is an important indicator of the status of a joint as the various degenerative and inflammatory arthritides directly affect the condition of the cartilage. In order to assess the precision of thickness measurements of hyaline articular cartilage, we undertook a pilot study using MR imaging, plain radiography, and ultrasonography (US). We measured the cartilage of the hip and knee joints in 10 persons (4 healthy volunteers and 6 patients). The joints in each patient were examined on two separate occasions using each modality. In the hips as well as the knee joints, the most precise measuring method was plain film radiography. For radiographs of the knees obtained in the standing position, the coefficient of variation was 6.5%; in the hips this figure was 6.34%. US of the knees and MR imaging of the hips were the second best modalities in the measurement of cartilage thickness. In addition, MR imaging enabled the most complete visualization of the joint cartilage. PMID- 1591126 TI - Radiologic approach to bile duct cysts in adults. AB - Radiologic findings in 7 adult patients with bile duct cysts were reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 6 patients, percutaneous transhepatic cholangiography (PTC) in 4, CT and ultrasonography (US) in 4, and angiography in 6. ERCP and PTC were the only methods which exactly showed the extent of the cysts and the anomalous pancreatico-biliary junction present in 5 patients. ERCP and PTC were mandatory for surgical planning and treatment. Pancreas divisum was revealed in 3 patients, all of whom had suffered from acute pancreatitis. Intracystic adenocarcinoma was depicted at cholangiography in 2 patients. US and CT were valuable in showing cystic masses between the pancreatic head and the hilum of the liver, but in no patient was the diagnosis made by any of these methods. Angiography was performed for preoperative vascular mapping. PMID- 1591127 TI - Regenerative nodules in hepatic cirrhosis. Value of gradient-echo MR imaging with a surface coil. AB - To evaluate the accuracy of surface coil gradient-echo (GRE) imaging in the detection of regenerative nodules of hepatic cirrhosis, 53 patients with diffuse liver disease, among whom 31 had cirrhosis, were prospectively investigated. Three GRE sequences acquired with a surface coil were used in the study: a T2* weighted, a T1-weighted, and a gadopentetate-enhanced sequence. ROC analysis showed that two surface coil GRE sequences were superior to conventional T2 weighted spin-echo imaging acquired with a body coil for the detection of regenerative nodules. The detection of regenerative nodules was also more accurate for the diagnosis of cirrhosis than the measurement of the caudate-to right lobe ratio. These results suggest that there could be a potential for surface coil GRE imaging in the assessment of the characteristic macroscopic alterations of cirrhosis. PMID- 1591128 TI - CT and angiography in chronic liver disease. AB - Detailed correlation of CT and angiographic findings in a retrospective analysis of 25 cases of portal hypertension is presented. The largest diameters of the common and proper hepatic arteries, the portal, splenic, and superior mesenteric veins, and perigastric veins were measured by the two methods, including a CT control series of 20 subjects. The splenic transverse diameter was also measured. Portosystemic collaterals and concomitant pathology disclosed by the two methods were compared. A ratio of nearly 1 was found between vessel diameters measured by angiography and CT, and about 1.3 for splenic size, applying uncorrected measures from angiographic films and a vernier caliper on CT studies. The diameters of hepatic arteries, splenic, and superior mesenteric veins and spleens were significantly larger than those of controls. Except for demonstrating arterial details and esophageal varices, CT was found equal or superior to angiography in mapping portosystemic collaterals, and to disclose concomitant pathology. PMID- 1591129 TI - Liver trauma and transection of the inferior vena cava. Sentinel contrast sign and hepatic perivenous tracking. AB - CT of a child with severe liver trauma due to a seat belt injury demonstrated avulsion of a portion of the lateral segment of the left lobe of the liver. The location of nondependent extravasated contrast material aided in identification of the visceral fracture site (the sentinel contrast sign). Associated transection of the inferior vena cava was evidenced by hypoattenuating zones adjacent to all the major hepatic veins and vena cava (hepatic perivenous tracking). Recognition of these two signs is important so that the radiologist can help the surgeon select the optimal operative approach. PMID- 1591130 TI - In vivo 19F MR spectroscopic study of metabolism of 5-fluorotryptophan in rat liver. AB - The metabolism of 5-fluorotryptophan in rat liver was examined by in vivo 19F MR spectroscopy. After i.v. injection of 200 mg/kg b.w. of 5-fluorotryptophan the substance was noted immediately as a strong peak, which decreased gradually. Another peak appeared about 40 min after the injection. The chemical shift value of this peak was 1.6 ppm from that of 5-fluorotryptophan. Kynurenine is known to be a major metabolite of tryptophan in the liver. We synthesized 5 fluorokynurenine from 5-fluorotryptophan by ozonolysis. The chemical shift value of 5-fluorokynurenine was confirmed to be coincident with that of the metabolite peak. This strongly suggests that the metabolite peak of 5-fluorotryptophan observed in this study was the 5-fluorokyrurenine signal. We also applied this method for the CCl4-injured liver. In the liver injury group, the metabolite peak appeared slowly and the intensity was low compared to that of the normal group, though the peak of 5-fluorotryptophan decreased similarly as in the normal liver. These results suggest that the decrease of 5-fluorotryptophan is due mainly to the renal excretion, as the injured liver could not metabolize 5 fluorotryptophan. PMID- 1591131 TI - Differential diagnosis of adrenal masses using out-of-phase FLASH imaging. A preliminary report. AB - The purpose of this report was to suggest the ability to differentiate adrenal masses by out-of-phase FLASH imaging. The images were obtained with breath holding at TR/TE 100/12 ms, flip angle 20 degrees. The material included adrenal adenoma (n = 16), nodular hyperplasia (n = 1), pheochromocytoma (n = 5), and adrenal metastatic tumors (n = 7). The signal intensity ratios of the adrenal mass/the diaphragmatic crus, back muscle, and renal cortex were obtained. The mean values of the ratios of adenomas or nodular hyperplasia were significantly different from pheochromocytomas or metastases. Although the number of adrenal masses was fairly small, the ratios of adrenal mass/diaphragmatic crus could distinguish them with no overlapping case. All 17 masses with the ratio of 1.16 or less were adenomas or nodular hyperplasia, whereas all 12 masses with a ratio greater than 1.23 were pheochromocytomas or metastases. This result suggests the ability of out-of-phase FLASH imaging to differentiate adrenal masses. PMID- 1591132 TI - Concomitant changes in MR image and morphology induced by glucose and fructose in B16 mouse melanomas. AB - The short proton relaxation times in the MR images of malignant melanomas make them different from most other tumors. We have previously shown that the T1 and T2 signals may be significantly influenced when the water distribution of the tumor is changed in vivo and in vitro. In the present work T1 and T2 were estimated and compared with the electron microscopy picture in subcutaneously implanted B16 melanomas in mice. Two hours after the mice were given an i.p. injection of 0.9% NaCl containing 10% glucose and 10% fructose (9 mice) both the T2 components were markedly and the T1 slightly prolonged. At the same time the electron microscopy picture displayed swelling of the melanocytes together with a marked decrease in number and size of their mitochondriae. There were no changes in the MR image or the melanocyte structure in control mice injected with 0.9% NaCl (9 mice) or 0.9% NaCl containing 10% fructose. It is concluded that the changed MR image may be coupled to the metabolism in melanoma. PMID- 1591133 TI - Phagocytic properties of granulocytes after intravenous injection of ioxaglate or iohexol. AB - To evaluate the influence of radiographic contrast media (CM) on human granulocytes, the ability of these cells to ingest latex particles after intravenous injection of ioxaglate and iohexol was investigated. Both CM inhibited the phagocytic properties of granulocytes; the inhibition was the most pronounced immediately after the injection, but inhibition was also observed 60 min after injection of ioxaglate. The inhibition 1 and 5 min after injection of CM was more pronounced after injection of ioxaglate than after injection of iohexol. However, this difference between the 2 CM was not significant. Significant inhibition of phagocytosis was found for mannitol solutions with osmolalities higher than 369 mOsm/l. Significant inhibition of phagocytosis was observed when granulocytes were isolated with either Hypaque/Ficoll or Percoll gradient centrifugation and then incubated with diatrizoate. Thus the ability of granulocytes to phagocytize latex particles was inhibited after i.v. injection of 50 ml ioxaglate or iohexol. Part of this inhibition may be due to hyperosmolality. PMID- 1591134 TI - Lack of correlation between ulnar variance and carpal bone angles on lateral radiographs in normal wrists. AB - It has been proposed that negative ulnar variance is a predisposing factor to development of posttraumatic carpal ligamentous instability. However, this implies that no correlation exists between ulnar variance and carpal bone angles in the normal wrist. Carpal bone angles on lateral wrist radiographs and ulnar variance were measured in a series of 75 normal wrists. The mean ulnar variance was -0.03 mm (SD 1.56, range -5 to 5). The correlation coefficients were 0.06, 0.11, and -0.05 between the ulnar variance, and radiolunate, radioscaphoid, and scapholunate angles, respectively. A correlation between the carpal angles on lateral wrist radiographs, and ulnar variance in normal wrists could not be demonstrated, suggesting that the presence of negative ulnar variance may serve as an impartial clue to the presence of ligamentous instability. PMID- 1591135 TI - Time-resolved transillumination of the breast. PMID- 1591136 TI - Ultrasound guided nephrostomy utilizing a one-step balloon catheter. Introduction of a new technique. PMID- 1591137 TI - Single exposure dual-energy subtraction radiography of the upper airways using computed radiography. PMID- 1591138 TI - New trends in international magnesium research. PMID- 1591139 TI - Magnesium distribution in rats after maximal exercise in air and under hypoxic conditions. AB - Variations in serum levels and distribution of Mg in the heart, gastrocnemius, liver and kidney in rats were studied after exercise to exhaustion in air (normoxia) and during hypoxia (FIO2 = 0.10). After exercise serum Mg concentrations increased significantly in air, but not during hypoxia. At rest, they increased significantly during hypoxia. In air, increases in Mg in the gastrocnemius and liver were found after exercise. At rest in hypoxia, Mg was reduced in heart, liver and kidney. After exercise in hypoxia, Mg was decreased in heart, gastrocnemius and liver, the greatest decrease occurring in the gastrocnemius, with a relative increase in kidney. Exercise and hypoxia both affect magnesium homeostasis. PMID- 1591140 TI - Triamterene may preserve lymphocyte magnesium and potassium in patients with congestive heart failure. AB - Electrolyte abnormalities are a frequent and potentially hazardous complication in the treatment of patients with congestive heart failure. Medical treatment with diuretics and/or digitalis, as well as neurohumoral activation most likely initiated by the compromised cardiac function, contributes to this alteration. The addition of potassium- and magnesium-sparing diuretics (triamterence, amiloride) to therapy with frusemide or hydrochlorothiazide is of possible value in preventing intracellular electrolyte abnormalities. PMID- 1591141 TI - Hypomagnesaemia-induced hypocalcaemia: concentrations of parathyroid hormone, prolactin and 1,25-dihydroxyvitamin D during magnesium replenishment. AB - Three patients with hypomagnesaemia-induced hypocalcaemia were investigated during the phase of magnesium replenishment. Before treatment, serum levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D were at the lower limit of normal. In spite of a rapid rise of parathyroid hormone (PTH) after intravenous administration of magnesium, a reactive increase in 1,25-dihydroxyvitamin D in serum was absent or delayed. The increase of serum calcium into the normal range occurred before any consistent change in the concentrations of this vitamin D metabolite. The rise of serum prolactin in response to the increase in PTH was blunted or absent, and is a further example of a transient PTH resistance during the phase of magnesium replenishment. PMID- 1591142 TI - Mechanisms of hypocalcaemia in the clinical form of severe magnesium deficit in the human. AB - Severe magnesium depletion leading to hypocalcaemia has been described in a variety of clinical settings. Inadequately low concentrations of parathyroid hormone (PTH) are a constant feature of hypomagnesaemic hypocalcaemia (HMHC), while target organ resistance to PHT in kidneys and bone may be demonstrated in the majority of these patients. The failure of membrane-bound adenylate cyclase in the parathyroids, kidneys and bone, thought to be the most important molecular mechanism in HMHC, cannot explain the concomitant resistance to vitamin D and its metabolites. In recent years, information has accumulated on further magnesium dependent intracellular events and alternative pathways of transcellular signalling. This may eventually allow the identification of one or more further biochemical mechanisms leading to hypocalcaemia in severe magnesium deficiency. PMID- 1591143 TI - The parathyroid hormone- 1,25-dihydroxyvitamin D endocrine system and magnesium status in insulin-dependent diabetes mellitus: current concepts. AB - Insulin-dependent diabetes mellitus (IDDM) is a chronic metabolic disorder which can induce alterations in bone metabolism (osteopenia) and/or in mineral homeostasis, mainly during growth. Some data suggest that these alterations may be related to low serum magnesium values found in IDDM that induce a functional hypoparathyroid state. In this paper, some aspects are revised relating to altered magnesium and mineral homeostasis in children with IDDM and their possible relationships. The role of osteocalcin, a specific osteoblast protein product, as a biochemical marker of diabetic osteopenia is also discussed. In addition, on the basis of personal experience, it is shown that the deranged parathyroid hormone-vitamin D axis in IDDM is reversed after normalization of magnesium serum levels by oral magnesium. Thus available data suggest that hypomagnesaemia is involved in the genesis of the altered mineral metabolism in children with IDDM. PMID- 1591144 TI - Influence of magnesium on the in vitro synthesis of 24,25-dihydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3. AB - The role of magnesium in the regulation of 25(OH)D3-24R-hydroxylase and 25(OH)D3 1 alpha-hydroxylase in vitro remains to be clarified. Using a radiochemical assay, the effect of substrate concentration on both enzymes was measured in rat kidney homogenates as well as the alterations in their kinetic behaviour resulting from changes in the magnesium concentration in the incubation medium. The results showed that magnesium could be a modulator of 24- and 1 alpha hydroxylases. Variations in magnesium caused alterations in the kinetic behaviour of both enzymes, which altered the synthesis rates of 24,25(OH)2D3 and 1,25(OH)2D3. Moreover, the substrate concentration was clearly involved in the response of both enzymes to the modulation by magnesium. PMID- 1591145 TI - A review of magnesium intake in the elderly. A cause for concern? AB - Elderly people in the United States represent an emerging high risk group for nutritional deficiencies. A magnesium deficit in the elderly can occur due to inadequate nutrient intakes, multiple drug use, or altered gastrointestinal function. Magnesium has been targeted as a risk factor for elderly people and has been implicated in the aging process. Data presented in this review confirm decreased availability of magnesium in the food supply, lower intakes of magnesium by elderly people, and widespread supplementation practices. Conflicting data exist regarding levels of magnesium in the blood and magnesium status in the elderly. It is not known to what extent suboptimal intakes may affect the aging process; however, magnesium-deficient conditions have been associated with neuromuscular and cardiovascular disorders, endocrine disturbances, insulin resistance and Alzheimer's disease. PMID- 1591146 TI - Chronic fatigue syndrome and chronic primary magnesium deficiency (CFS and CPMD). PMID- 1591147 TI - Nursing in Europe: making the links. PMID- 1591148 TI - HIV/AIDS: a place between pillar and post. Interview by Charlotte Alderman. PMID- 1591149 TI - Availability of grants for nursing research. PMID- 1591150 TI - Accidents in elderly care: a randomised controlled trial (Part 1). AB - This paper reports the data on accidents from a randomised controlled trial evaluating health authority-funded nursing home and long stay care of the elderly ward care in one inner London health district. Respondents randomised to NHS nursing homes experienced a higher accident rate than respondents randomised to conventional long stay hospital wards for elderly people. Respondents in the homes also experienced an earlier decline in functional and mental ability than those in hospital. These disadvantages have to be balanced against the previously published observational data from the evaluation, which clearly indicated that quality of life in the homes was superior to that in the wards. The conclusion from this study is that earlier decline in functional and mental ability and increased accident risk in the more flexible environments of the nursing homes have to be balanced against an inferior quality of life in the large hospital long stay wards. PMID- 1591151 TI - Parenting assessment: the parent/child game. PMID- 1591152 TI - Dilemmas in setting quality standards. AB - Setting standards of care is an activity which requires creativity, but may lead nurses into conflict. Issues such as nurse accountability, understanding of the nurse's role and the philosophy of the organisation in which the nurse works, will affect and complicate the process of standard setting. Ultimately, it is suggested, consultation to discover what the patient defines as quality care may provide the most effective means of reducing the conflict. PMID- 1591153 TI - Managing to manage. PMID- 1591154 TI - Holistic or unrealistic? PMID- 1591155 TI - Whistleblowing: a professional duty. PMID- 1591156 TI - Cardiology update. Implantable defibrillators. PMID- 1591157 TI - Cardiology update. Audit in cardiology. PMID- 1591158 TI - Cardiology update. Hope and charity. PMID- 1591159 TI - Cardiology update. Cardiac rehabilitation. PMID- 1591160 TI - World conflict: better builders than fighters. Interview by Norah Casey. PMID- 1591161 TI - A national census of practice nurses. PMID- 1591162 TI - Preventing pressure sores in the elderly. PMID- 1591163 TI - Accidents in elderly care: a randomised controlled trial (Part 2). AB - This paper reports the data on accidents from a randomised controlled trial evaluating health authority-funded nursing home and long stay care of the elderly ward care in one inner London health district. Respondents randomised to NHS nursing homes experienced a higher accident rate than respondents randomised to conventional long stay hospital wards for elderly people. Respondents in the homes also experienced an earlier decline in functional and mental ability than those in hospital. These disadvantages have to be balanced against the previously published observational data from the evaluation, which clearly indicated that quality of life in the homes was superior to that in the wards. The conclusion from this study is that earlier decline in functional and mental ability and increased accident risk in the more flexible environments of the nursing homes have to be balanced against an inferior quality of life in the large traditional hospital wards; such assessments are not easy to make on behalf of other people. The report is divided into three parts. This week, the results of the trial are presented. PMID- 1591164 TI - New structures for nurse education. AB - There are major changes taking place in the structure and organisation of nurse education. These include the amalgamation of schools and colleges of nursing, the development and formalisation of links with higher education, changes in funding arrangements introduced in April 1991, and the effects of Working Paper 10 (1), which requires schools and colleges of nursing to function in the purchaser/provider environment. As a result of these factors, particular attention is being focused on the organisational structures which are emerging in nurse education institutions. The author considers briefly the concept of organisational structure, including factors to be addressed in choosing and developing appropriate structures for specific organisations. The traditional bureaucratic structure common in nurse education establishments is discussed and evaluated and consideration is given to the development of more appropriate structures for these newly emerging nurse education institutions. PMID- 1591165 TI - Behavioural disturbance: correlating incident and response. PMID- 1591166 TI - Nurses working with commercial sponsors. PMID- 1591169 TI - Communication: cut the cover-ups. PMID- 1591168 TI - Seclusion: a last sanctuary? PMID- 1591167 TI - On being a primary or associate nurse. PMID- 1591170 TI - Tradimus. Students at centre stage. PMID- 1591171 TI - Tradimus. Whistleblowing: nursing? Whistle for it. PMID- 1591172 TI - Tradimus. Whistleblowing: casting the first stone. PMID- 1591173 TI - Tradimus. Student support: stress fractures. PMID- 1591174 TI - Tradimus. Sex equality: second class male? PMID- 1591175 TI - Tradimus. Conference report: the students' agenda. PMID- 1591177 TI - HIV/AIDS. DoH details payments for HIV-transfer cases. PMID- 1591176 TI - Tradimus. RCN Student Bill of Rights. PMID- 1591178 TI - Whistleblowing. Swept out to sea. PMID- 1591179 TI - Financial management: an exercise in juggling. PMID- 1591180 TI - Intensive care: monitoring central venous pressure. PMID- 1591181 TI - Students' perceptions of Project 2000. PMID- 1591182 TI - Nursing development units: developing clinical practice in Liverpool. PMID- 1591183 TI - Nurse management and leadership today. AB - Government health service reforms and the development of the Strategy for Nursing have forced a rethink of the attitudes, values and skills required to function in the new-style organisation. The thrust is towards alternative approaches to service provision and delivery, which increase the complexity of managing in today's health service. Nurses can influence the delivery of care in a proactive way, but there appears to be a crisis of confidence in nurse management and leadership. Measures to overcome this emphasise the need to develop sound continuing education programmes for nurses who manage. Individual performance review, cascaded to staff nurse level, is recommended as a positive means of encouraging individuals to develop their careers. Nurses are invited to take part in the reforms as a way of realising their own management talents. PMID- 1591184 TI - Health passport. PMID- 1591186 TI - Working parents: a woman's rightful place. PMID- 1591185 TI - The Clay column. PMID- 1591187 TI - Skill mix: the myth of basic care. PMID- 1591188 TI - A day in the life: occupational emergency. PMID- 1591189 TI - Communication: born to be mild. PMID- 1591190 TI - An acting nurse tutor. PMID- 1591191 TI - Psychiatric nursing: we don't do mad people now. PMID- 1591192 TI - Adult third ventricle width and infant behavioral arousal in groups at high and low risk for schizophrenia. AB - Previous research has demonstrated: (1) Subjects who are at genetic high risk for schizophrenia and who suffer delivery complications are at increased risk to evidence a widened third ventricle. (2) A widened third ventricle is related to decreased ANS arousal and, among schizophrenics, is related to negative symptom schizophrenia. (3) Adult schizophrenics evidence behavioral analogues of negative symptom schizophrenia premorbidly. This study compared adult CT scans to ratings of infant behavior in 179 subjects (104 at high genetic risk for schizophrenia) with the hypothesis that widened third ventricles would be related to underaroused infant behavior. Results of an ANOVA suggest that subjects who are at genetic high risk for schizophrenia and who evidence a widened third ventricle are more likely to have shown signs of behavioral underarousal as infants. Possible explanations, implications and limitations of the study are discussed. PMID- 1591193 TI - Planum temporale in schizophrenia: a magnetic resonance study. AB - Magnetic resonance imaging (MRI) scans were used to examine the size and asymmetry of the planum temporale (PT) in 20 schizophrenic patients and 12 strictly matched healthy volunteers. PT lengths from coronal sections were measured and then summed to obtain an estimate of their areas. Schizophrenics showed the lack of the physiological PT area asymmetry evidenced in the control sample and a statistically significant diagnosis by side interaction was observed (F = 4.96; p less than 0.05). The study of PT asymmetry could permit us to better analyse the role of laterality in the pathophysiology of schizophrenia. PMID- 1591194 TI - Loss of sylvian fissure asymmetry in schizophrenia. A quantitative post mortem study. AB - The sylvian fissure is known to be one of the most asymmetric structures of the human brain. Sylvian fissure length was measured in post-mortem brains of 35 schizophrenic patients and 33 matched non psychiatric control subjects. The schizophrenics showed a significantly reduced length of the left sylvian fissure (-16%, p less than 0.0001) compared to the control subjects, while the right sylvian fissure length was unchanged. Sylvian fissure asymmetry (left/right ratio) was more reduced in male schizophrenics (-24%, p less than 0.001) than in female patients (-16%, p less than 0.03). This finding is consistent with several post-mortem and MRI studies showing left temporal lobe pathology in a significant proportion of patients and may indicate that schizophrenia is a disorder of early neurodevelopment causing impaired cerebral lateralization. PMID- 1591195 TI - Schizotypal personality disorder in individuals with and without schizophrenic relatives: similarities and contrasts in neurocognitive and clinical functioning. AB - Schizophrenia-spectrum disorders may reflect the genotype for schizophrenia. One such disorder, Schizotypal Personality Disorder (SPD), was examined as a function of family history of schizophrenia. Clinical profiles and neurocognitive functioning were evaluated in 25 schizotypal subjects (10 SPD with schizophrenic relatives and 15 SPD without schizophrenic relatives), and in 24 normal controls. The primary finding is that vigilance performance was similarly impaired in both SPD groups. An additional neurocognitive impairment, comprehension of grammatical constructions, was observed only in the SPD group with schizophrenic relatives. Of interest, the clinical profiles of the two SPD groups did not differ significantly. These results suggest that schizotypal personality disorder is associated with a continuum of neurocognitive vulnerability that increases as a function of family history of schizophrenia. PMID- 1591196 TI - Seasonal patterns of recurrence in schizophreniform psychosis. AB - Patterns of recurrence were studied in 54 patients with a diagnosis other than affective illness, who had had 4 or more episodes, each lasting less than 6 months. Their diagnoses for the last hospitalization were: schizophrenia in 46 cases, 'catatonia' in 3 cases and atypical psychosis in 5 cases. Six patients (11%) fulfilled criteria nearly comparable to the DSM-IIIR diagnostic criteria for seasonal patterns. This prevalence is significantly higher than expected by chance and suggests that seasonal recurrence is not confined to affective illness. Four others showed an apparent periodicity shorter than 12 months, a finding which suggests that an endogenous circannual rhythm was at work in these cases and possibly also in some of the cases with an apparent seasonality of recurrence. PMID- 1591197 TI - Implicit learning in psychotic patients. AB - Implicit verbal learning of psychotic patients (n = 59) and non-psychotic control patients (n = 20) was studied using stem completion and association tasks in lexical and semantic priming paradigms. Performance on these tasks was contrasted with explicit memory on Rey's verbal learning test. Furthermore, correlations of these aspects of memory with positive and negative symptoms of psychosis were examined. Symptom ratings were based on an interview by a psychiatrist using the CPRS and SANS. As expected, the lexical and semantic priming effects in both patient groups were not significantly different, whereas the psychotic patients compared to the controls were impaired in explicit learning. None of the memory variables was significantly correlated with negative or positive symptoms. These findings are explained by the fact that priming effects, as opposed to explicit learning, depend on automatic memory processes, which do not require conscious effort. Moreover, the findings suggest the intactness of posterior cortical functions in psychotic patients. PMID- 1591198 TI - Gender differences in schizophrenia. Results of a follow-up study from India. AB - As part of the study on 'Factors affecting the course and outcome of schizophrenia' at Madras, India, 96 schizophrenic patients who fulfilled Feighner's criteria were followed up closely. Of these, 67 patients who completed 5 years of follow-up were studied with respect to gender differences in sociodemographic and clinical variables at inclusion and follow-up, course of illness and outcome. Women were found to have a better outcome. The various factors contributing to this are discussed in the context of the Indian setting. PMID- 1591199 TI - Left turning (swivel) in manic patients. AB - Nineteen bipolar inpatients in manic episodes and 19 normal control subjects were tested on a two-button task which required turning (swiveling) 180 degrees to collect coin-reinforcers. Significantly more right-handed (8/16) manic patients turned left (consistently 16 times to collect reinforcement) than right-handed normal controls (1/15), most of whom turned consistently right 16 times. Right handed manic patients were also significantly slower with both hands on a motor sequencing task (Pin Test) than the normal controls. Left hemi-spatial preference may be linked to asymmetric striatal dopaminergic activity common to all psychoses. PMID- 1591200 TI - Depressed nocturnal plasma melatonin levels in drug-free paranoid schizophrenics. AB - The 24-h profiles of plasma melatonin and cortisol were evaluated in 7 drug-free male paranoid schizophrenics and in 7 healthy subjects matched to the patients for age, sex, body weight, height and season of testing. Blood samples were obtained at 20.00, 22.00, 24.00, 01.00, 02.00, 06.00, 08.00 and 12.00 h. Light was turned off from 21.00 to 07.00 h. Compared with that of the normal controls, the circadian rhythm of plasma melatonin was absent in paranoid schizophrenics (F7.84 = 7.30, p less than 0.0001; two-way ANOVA with repeated measures) whereas the 24-h profile of plasma cortisol was preserved, although at a slightly higher level (F1.12 = 26.810, p less than 0.0002). The melatonin/cortisol ratio was significantly higher in healthy subjects than in the schizophrenic patients. A functional relationship between disturbances in the melatonin rhythm especially and schizophrenia may be proposed, although the significance of this relationship remains to be elucidated. PMID- 1591201 TI - Assessment of dementia in elderly schizophrenics with structured rating scales. AB - Although a number of elderly institutionalized schizophrenic patients appear to suffer from dementia, little is known about the characteristics of the cognitive impairment or its prevalence in this population. In order to answer these questions it is necessary to first reliably and validly assess dementia in elderly schizophrenic patients. This paper reports the results of a study examining the reliability of assessments of the severity of dementia in schizophrenia using scales designed for other dementing conditions and examining the convergence of ratings of the severity of dementia generated from all available sources of information (patient, caregiver, and chart) versus the chart alone. It was found that the interrater reliability of these ratings was very high. On the other hand ratings generated from the hospital chart alone, without contact with either the patient or caregiver, manifested a systematic bias toward overestimation of the severity of dementia. These results suggest that dementia assessment in schizophrenia does not require different instrumentation from that used in other conditions but that relying on the medical chart alone would induce a systematic bias in the results. PMID- 1591202 TI - Schizophrenia and leprosy. The potential for multiple interactions. A case report. PMID- 1591203 TI - Corneal light scattering after excimer laser photorefractive keratectomy: the objective measurements of haze. AB - BACKGROUND: After photorefractive keratectomy using excimer lasers (193 nm), most corneas show a marginal loss of transparency (haze) and the assessment of its magnitude in clinical studies has been subjective. To address this problem, we have developed a new device for the objective measurement of haze by measuring corneal light scattering. METHODS: A CCD-camera was fixed at 40 degrees to a slit lamp microscope and connected via frame-grabber to a computer. By incorporating polarizing filters, the system could discriminate between reflected and scattered light. The intensity of light coming from the cornea was measured in gray scale levels using in-house image analysis software. The system was calibrated against three different sizes of microspheres (0.25, 0.50, and 5.00 microns) which corresponded to the size of cellular and extracellular elements known to occur at sites of corneal surgery. Data were obtained from three treated human eyes with measurements before treatment and at five different postoperative intervals with a maximum follow up of 4 months. RESULTS: All three sizes of microspheres caused disturbances in gray scale levels (36 to 255 units) in the same range of those observed in corneal measurements. Disturbances in corneal light scattering were noted from 1 week postoperatively and persisted throughout the period of observation. We observed an increase in reflected and scattered light until the 2nd postoperative month followed by a subsequent decline. CONCLUSIONS: It appears that this device is very useful to defect and measure objectively disturbances in corneal transparency after excimer laser photorefractive keratectomy. PMID- 1591205 TI - Biomechanics of the cornea--who needs it? PMID- 1591204 TI - Delayed sterile keratitis following radial keratotomy successfully treated with conjunctival flap. AB - BACKGROUND: A case of sterile keratitis involving three adjacent incisions and intervening stroma occurring 5 years after an eight-incision radial keratotomy is reported. METHODS: Multiple cultures showed no pathogens. Treatment with antibiotics, lubricants, patching, and bandage contact lenses failed to improve the condition. A conjunctival bridge flap was therefore performed. RESULTS: Total resolution of the keratitis occurred rapidly after performing the conjunctival bridge flap. CONCLUSIONS: Delayed keratitis following radial keratotomy has been reported in the past. Treatment in these cases has primarily been corneal transplantation. The present case presents an alternative treatment, conjunctival bridge flap, which was successful in this case of sterile keratitis following radial keratotomy. PMID- 1591206 TI - Computational methods advantageous for ophthalmology. PMID- 1591208 TI - Does Bowman's layer determine the biomechanical properties of the cornea? AB - BACKGROUND: Bowman's layer is believed to be the stabilizing element of corneal curvature due to its assumed mechanical stiffness. METHODS: Uniaxial stress strain analysis was performed in paired corneal strips to compare the contribution from Bowman's layer. Two central strips were taken from each cornea and Bowman's layer was removed from one of them with the excimer laser. RESULTS: Pairwise comparison yielded no statistical difference in elastic or viscoelastic properties according to presence or absence of Bowman's layer. At a strain of 2%, the stress was measured to be (5.06 +/- 2.01) x 10(3) N/m2 with Bowman's layer and (4.72 +/- 1.3) x 10(3) N/m2 without Bowman's layer. Also, the two relaxation times did not differ significantly. CONCLUSIONS: These findings imply that Bowman's layer does not contribute significantly to mechanical stability within the cornea. PMID- 1591207 TI - Introduction to biomechanics of the cornea. AB - BACKGROUND: As refractive procedures involving the cornea have proliferated, concerns over the long-term stability and predictability of these procedures have occupied a more prominent role. METHODS: Procedures and principles of mechanical engineering to mathematically model the cornea can provide valuable insight into the biomechanics of the cornea, and this approach can be used to predict corneal behavior. In order to utilize these advanced methods, some basic knowledge concerning limitations, assumptions, and techniques regarding the finite element method is needed. The principles of mechanical measurement of deformable bodies are discussed, as are the quantities stress, strain, Poisson's ratio, and creep as they are measured and used in the modeling of biologic systems. The finite element modeling procedure is discussed in a simplified geometric system. CONCLUSIONS: While work remains to be done in this area, it is seen that useful and predictive models can be created which significantly improve our understanding and predictability of corneal procedures. PMID- 1591209 TI - Computer modeling of wound gape following radial keratotomy. AB - BACKGROUND: The edges of radial keratotomy incisions remain separated by epithelium or new collagen. To determine if the amount of gape of the incision edges agrees with the induced corneal flattening, two mathematical models of the cornea were studied. METHODS: A finite element model of the eye was constructed; radial incisions through Bowman's membrane and stroma were simulated, as well as incisions confined to the stroma but not involving Bowman's or Descemet's membranes. Geometrical calculations were also performed in a second morphologic model of a spherical shell. RESULTS: The finite element and geometrical models agree closely on the corneal curvature change for a given incision gape. Both models predict that linear intrastromal incisions that do not involve Bowman's layer would not produce significant corneal flattening. CONCLUSIONS: Corneal flattening after radial keratotomy is closely related to incision gape, mediated through structural weakening of the cornea. Purely intrastromal radial incisions, as might be created with Nd:YAG lasers, prevent wound gape and would not appear to be a promising technique for flattening the cornea. PMID- 1591210 TI - Finite element based mechanical models of the cornea for pressure and indenter loading. AB - BACKGROUND: In this article, we examine the finite element method and its use in mechanical modeling of the cornea. METHODS: Both linear elastic and geometrically nonlinear models are considered. The effects of corneal geometry, boundary conditions, thickness, and the number of layers in the model are determined. RESULTS: Results indicate that, for intraocular pressure loading, the thickness and the choice of boundary conditions at the limbus are significant. CONCLUSIONS: A model of tonometry showed that simulating the layered nature of the cornea and including the increased flexibility of large deformation are critical. PMID- 1591211 TI - Computer simulation of arcuate keratotomy for astigmatism. AB - BACKGROUND: The development of refractive corneal surgery involves numerous attempts to isolate the effect of individual factors on surgical outcome. Computer simulation of refractive keratotomy allows the surgeon to alter variables of the technique and to isolate the effect of specific factors independent of other factors, something that cannot easily be done in any of the currently available experimental models. METHODS: We used the finite element numerical method to construct a mathematical model of the eye. The model analyzed stress-strain relationships in the normal corneoscleral shell and after astigmatic surgery. The model made the following assumptions: an axisymmetric eye, an idealized aspheric anterior corneal surface, transversal isotropy of the cornea, nonlinear strain tensor for large displacements, and near incompressibility of the corneoscleral shell. The eye was assumed to be fixed at the level of the optic nerve. The model described the acute elastic response of the eye to corneal surgery. RESULTS: We analyzed the effect of paired transverse arcuate corneal incisions for the correction of astigmatism. We evaluated the following incision variables and their effect on change in curvature of the incised and unincised meridians: length (longer, more steepening of unincised meridian), distance from the center of the cornea (farther, less flattening of incised meridian), depth (deeper, more effect), and the initial amount of astigmatism (small effect). CONCLUSIONS: Our finite element computer model gives reasonably accurate information about the relative effects of different surgical variables, and demonstrates the feasibility of using nonlinear, anisotropic assumptions in the construction of such a computer model. Comparison of these computer-generated results to clinically achieved results may help refine the computer model. PMID- 1591212 TI - Numerical modeling of radial, astigmatic, and hexagonal keratotomy. AB - BACKGROUND: A mechanical model of the human cornea is proposed and employed in a finite element formulation for simulating the effects of keratotomy on the cornea. METHODS: The formulation assumes that the structural behavior of the cornea is governed by the properties of the stroma which is modeled as a thick membrane. The tensile forces in the cornea are resisted by the collagen fibrils embedded in the ground substance of the stromal lamellae. When the stromal lamellae are cut, as in keratotomy, it is assumed that they no longer carry any tensile forces, and the forces in the cornea are then resisted only by the remaining uncut lamellae. A constitutive model, which represents the anisotropy and inhomogeneity in the membrane rigidity induced by the incisions, has been employed in a geometrically nonlinear finite element membrane formulation for small strains with moderate rotations. This preliminary model is restricted to linear material behavior with no time dependency. RESULTS: A number of numerical examples are presented to illustrate the effectiveness of the proposed constitutive model and the finite element formulation for computing the immediate postoperative shift in corneal power resulting from radial, astigmatic, and hexagonal keratotomy. Surgical changes computed using the proposed model compare well with surgical corrections predicted by expert surgeons. CONCLUSIONS: The proposed computational model of the cornea and the effects of surgical procedures on it is based on a number of important simplifying assumptions regarding the mechanical properties and structure of the corneal tissue at the ultrastructure level. The encouraging results found with present model suggest that further development and refinement will be useful. PMID- 1591213 TI - On the computer-aided and optimal design of keratorefractive surgery. AB - BACKGROUND: Several recent papers have discussed the use of engineering-based computer methods for the analysis of keratorefractive surgical procedures. What has been lacking is a broader view of the role of engineering analysis in keratorefractive surgery. This article demonstrates how these various analysis methods can be coupled to provide a comprehensive methodology for the design of refractive surgical procedures. METHODS: A structural model of the eye, based on a linearly elastic, transversely isotropic finite element formulation is coupled to a full-eye optical model. The optical errors due to refractive keratotomy are estimated by ray tracing through the optical model and measuring the position of the resulting focal plane relative to the retina. Computer-based optimization methods are employed to determine the surgical parameters necessary to correct myopia for a given set of surgical design goals. RESULTS: Results based on a hypothetical eye demonstrate agreement with clinical trends. Radial keratotomies are designed that eliminate refractive error while minimizing invasiveness in one case and maximizing the optical zone size in another. It is also shown that there is significant potential to customize this process on a patient-by-patient basis using clinically measured data. CONCLUSIONS: We present an overview of the research necessary to bring this approach to fruition. While only a first step, the methodology presented in this article has the potential to increase the predictability of keratorefractive surgery by substantially increasing both the quality and the quantity of the information available to the refractive surgeon preoperatively. PMID- 1591214 TI - A thin-shell model of the cornea and its application to corneal surgery. AB - BACKGROUND: We present a thin-shell, analytical model of the vertebrate cornea to study the changes in shape resulting from surgical operations (eg, radial keratotomy). METHODS: A simple closed-form solution is derived for a thin linearly elastic spherical model of the cornea. We assume that the shell is symmetrical about a central axis and that the modulus of elasticity is the same in all directions. The surgery is modeled by allowing the modulus of elasticity (or equivalently the thickness) of the shell to depend upon position, measured as an angle from the axis of symmetry. RESULTS: The analytical nature of the solution allows us to compute the principal curvatures of the cornea explicitly. For example, for representative parameters, the model predicts the average corneal curvature changes from about 43 diopters before keratotomy to about 38 D after keratotomy. CONCLUSIONS: The model is used to estimate Young's modulus from experimental data reported previously by Thomas et al (Invest Ophthalmol Vis Sci 1991;32:1000), as well as to investigate the effect of surgery on corneal flattening and the associated sensitivity to intraocular pressure changes. PMID- 1591215 TI - The role of T cells in the mediation of glomerular injury in Heymann's nephritis in the rat. AB - Heymann's nephritis (HN), a rat model of the membranous glomerulonephritis in man, is thought to be mediated by auto-Ig with subsequent activation of C. Whether T cell mechanisms are involved in the mediation of HN, apart from CD4+ cells providing help for auto-Ig production, was examined by treatment with mAb specific for T cell subsets for 6 weeks after immunization to induce HN. Anti-CD4 mAb therapy totally prevented proteinuria, in that at 6, 8, and 12 week treated rats had less than 15 mg/day of protein compared to controls that all had greater than 260 mg/day. Ig and C deposition in the glomerulus was significantly less and auto-Ig titers in serum were partially suppressed by anti-CD4 therapy. Anti-CD8 mAb therapy markedly reduced proteinuria at all time points, for example at 6 weeks there was 51 +/- 40 mg/day compared to 183 +/- 120 mg/day (P = 0.0003), but had no effect on auto-Ig titers or on Ig and C deposition in the glomerulus. A non-specific effect of high dose mouse mAb therapy was excluded by the findings that a mAb that did not bind to rat cells had no effect on the induction of HN and that serum C was not depleted in any of the mAb treated animals. A role for T effector mechanisms was further supported by the finding that therapy with mAb to T cell receptor alpha/beta chain or with cyclosporine also markedly delayed the onset of proteinuria. Examination of renal biopsies showed a T cell infiltrate in glomeruli and the interstitium of the untreated HN controls that was not present in MRC Ox35 or MRC Ox8 treated groups. This infiltrate included CD4+ and CD8+ T cells and macrophages. These results suggest induction of proteinuria in HN was totally dependent upon CD4+ T cells, and that CD4+ and CD8+ cells may have a direct role in the mediation of glomerular dysfunction in HN. PMID- 1591216 TI - CD8 expression alters the fine specificity of an alloreactive MHC class I specific T hybridoma. AB - The influence of CD8 on the fine specificity of MHC class I-restricted T cell allorecognition was evaluated by comparing the reactivity of CD8- and CD8 transfected forms of an allospecific, H-2Kb-restricted T hybridoma. The CD8- T hybridoma responded to cells expressing H-2Kb, H-2Kbm6, and the individual H-2Kb- --bm10 back mutations 165V----M, 173K----E, and 174N----L. Under the same conditions the CD8- T hybridoma responded poorly or not at all to cells expressing H-2Kbm10, H-2Kbm8, the individual H-2Kb----bm10 back mutants 163T----A and 167W----S, and the individual H-2Kb----bm8 back mutations 22Y----F and 24E--- S. In contrast, T hybridoma cells expressing high levels of CD8 reacted strongly with antigen presenting cells (APC) expressing H-2Kb and H-2Kbm6 molecules, as well as APC expressing H-2Kbm10 (weakly), H-2Kbm8, and all five individual H-2Kb- --bm10 and the two H-2Kb----bm8 back mutants 22Y----F and 24E----S. The mutations which distinguish the T cell recognition of both H-2Kbm10 and H-2Kbm8 from H-2Kb are predicted to control the interaction of these class I molecules with antigenic peptides in the binding site, implying an important role for peptide antigen in T cell allorecognition. Nonetheless, CD8 expression by the H-2Kb restricted T cells conferred novel or enhanced alloreactivity with cells expressing H-2Kbm10, H-2Kbm8, and each of the individual H-2Kb----bm10 and H-2Kb- --bm8 back mutants. These findings reflect an important role for CD8 in influencing the fine specificity of MHC class I recognition by T cells and may indicate a limited structural role for peptide antigen in defining the ligand recognized by these alloreactive T cells. PMID- 1591217 TI - Pulmonary eosinophilic response to respiratory syncytial virus infection in mice sensitized to the major surface glycoprotein G. AB - To investigate the contribution of immunity to individual respiratory syncytial (RS) virus proteins to the augmentation of pulmonary pathology, mice were scarified with recombinant vaccinia viruses (rVV) expressing individual RS virus proteins. The pulmonary response to infection with RS virus was monitored by bronchoalveolar lavage (BAL). In mice vaccinated with the major surface glycoprotein (G), 14-25% of BAL cells were eosinophils; these comprised less than 3% of BAL cells from other groups of mice after RS virus challenge. Mice sensitized to the G or fusion (F) proteins developed lung haemorrhage and those sensitized to G, F or nucleoprotein (N) showed pulmonary polymorphonucleocyte efflux. To investigate the concomitant changes in local T-cell subsets, BAL cells were stained with mAbs to CD4, CD8, CD45RB, alpha beta and gamma delta T cell receptor (TCR) proteins. Three colour flow cytometry showed that most cells were CD3+CD4+ alpha beta+gamma delta+ or CD3+CD8+ alpha beta+gamma delta-, although some CD4-CD8-SIg- cells were also identified. Most of these 'null' cells lacked CD3, but CD3+ null cells from rVV-G or -F primed mice bore either alpha beta and gamma delta TCR in approximately equal numbers. The intensity of staining for CD45RB declined rapidly after infection with RS virus on both CD4 and CD8 cells. The rate of loss of CD45RB on CD4 T cells was accelerated by prior sensitization with rVV-G, consistent with conversion to helper T cell subsets producing eosinophil-promoting cytokines. The eosinophilic reaction to RS virus infection therefore specifically reflects sensitization to G protein, but sensitization to other proteins can also cause distinct pathological effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591218 TI - Preferential VH/V lambda pairings occur in the available B cell repertoire of adult BALB/c mice. AB - To gain insights into the composition of the B cell repertoire, we have investigated VH gene family expression associated with individual light chains. For this purpose, we have examined the use of 12 VH gene families in a large collection of hybridomas expressing one of the four lambda light chains [lambda 1 (V1J1), lambda 2 (V2J2 and V x J2) and lambda 3 (V1J3)]. Our results show that the distribution of the VH families is very different from one lambda subtype to another. This suggests that a few substitutions between VL regions are sufficient to generate very different associated repertoires by strong selection mechanisms. Moreover, we assume that the global VH expression pattern is not random but rather composed of many preferential VH/VL associations. PMID- 1591219 TI - Intoxication of high affinity IL-2 receptor positive thymocytes blocks early stages of T cell maturation. AB - Early murine fetal thymocytes express functional, high affinity IL-2 receptors as determined by: (i) the presence of IL-2R beta chain (p75) mRNA; (ii) IL-2 (10 U/ml) induced cell proliferation/cellular maturation in lobe submersion cultures (LSC). Under the influence of IL-2, early thymocytes differentiate in vitro into more mature, early single positive CD4-CD8+ followed in vivo by double positive CD4+CD8+ and single positive CD4+CD8-T and CD4-CD8+ thymocytes. Specific intoxication of high affinity IL-2R positive thymocytes by recombinant interleukin-2-diphtheria toxin-related fusion protein (DAB486-IL-2) results in transient, dose dependent blockade of in vivo and in vitro thymocyte maturation. DAB486-IL-2 induced effects upon in vivo maturation are reversible within 2 weeks after cessation of drug administration. Taken together, these results demonstrate the expression of functional, high affinity IL-2 receptors on early thymocytes. Elimination of high affinity IL-2 receptor positive thymocytes with DAB486-IL-2 results in transient blockade of T cell maturation. Since DAB486-IL-2 is now in clinical trial, it is reassuring to note that it does not permanently disrupt thymic maturation. PMID- 1591220 TI - Characterization and partial purification of a novel cytotoxic lymphokine (factor 2) produced by a human B cell line (Karpas 160). AB - A subclone (160b) of the human B cell (Karpas 160) was shown to produce a novel cytotoxic lymphokine [Factor 2 (F2)] in addition to tumour necrosis factor alpha (TNF-alpha) and beta (TNF-beta). F2 was found to have selective toxicity to numerous human tumour cell lines, particularly the erythroleukaemic cell line K562, whereas TNF-alpha/beta were not cytotoxic to these cells, even at relatively high concentrations. Our studies have shown that F2 activity in crude preparations is heterogeneous both in its molecular weight, isoelectric point (pI) and hydrophobicity, which depends not only on the source of F2 cytotoxicity but also on the conditions of methods for its production. Our studies also showed that F2 was separable from TNF by DE52, S-300 gel filtration and Rotofor isoelectric focusing. F2 was partially purified up to 1000-fold by two procedures. The major active form, as assessed by gel filtration was of mol. wt of 45-67 kDa. On SDS-PAGE, F2 activity was recovered mainly from two regions of the gels corresponding to 10-14 kDa and 60-70 kDa. Antibodies of human TNF-alpha, TNF-beta, IFN-alpha, IFN-gamma, and TGF-beta failed to prevent F2-mediated cytotoxicity to K562. F2 activity was not inhibited by mannose-6-PO4 or mouse mAb to rat granule content, both of which have been reported to block human natural killer cytotoxic factor. Our studies indicated that F2 is likely to be a distinct human cytokine with selective cytotoxic activity against tumour cells. PMID- 1591221 TI - New synthetic analogs of lipid A as lipopolysaccharide agonists or antagonists of B lymphocyte activation. AB - We have studied the ability of synthetic analogs of lipid A to mimic lipopolysaccharide (LPS) for activation of 70Z/3 pre-B cells (expression of surface Igs) or to antagonize this effect. The results indicate that the presence of glucosamine (mono- or disaccharide) as a 'backbone' for the attachment of fatty acids is not necessary for activation of cells of the B lineage. Phosphate groups are not necessary either. Other structural features such as the configuration of particular asymmetric carbons, and the distance between an anionic group and an N-acyl chain, seem to be much more critical parameters for activation of B cells. Among the synthetic lipids which were unable to activate 70Z/3 cells, one compound, consisting of N,N-acylated and bisphosphorylated 2,3 dideoxy-2,3-diamino-D-glucose, behaved as a specific LPS antagonist and blocked also the activation triggered by the other synthetic inducers. The influence of the synthetic lipids on the entry of mature mouse B lymphocytes into the G1A phase of the cell cycle (cell enlargement) was also investigated. A high correlation was observed between the potency to activate pre-B cells and the ability to induce blast formation in mature B cells. PMID- 1591222 TI - Early cellular and molecular events in inflamed skin: an integrated concept. PMID- 1591223 TI - Monoclonal anti-melanoma antibodies IKH-1 and IKH-2 which work on formalin-fixed, paraffin embedded tissues: characterization, clinical trials and comparative studies with HMB-45. AB - Mouse monoclonal antibodies (MoAbs), IKH-1 and IKH-2, were produced against cloned human melanoma cells, KHm-6, which were cultured with 12-O tetradecanoylphorbol-13-acetate (TPA) and processed by formalin fixation and alcohol dehydration (FFAD). According to the biochemical analysis, antigenic substances which reacted with IKH-1 were 34.0-60.0 kDa glycoproteins, and those which reacted with IKH-2 were 33.5, 34.5 and 36.0 kDa glycoproteins. Immunoelectron microscopy revealed that reaction products of IKH-1 were seen in some membranous vesicles, premelanosomes and cell membrane of TPA-treated KHm-6 cells, while IKH-2 recognized only premelanosomal structures. Immunohistochemical tests revealed that IKH-1 and IKH-2 have a high sensitivity (94.0% and 85.0%, respectively) to formalin-fixed, paraffin-embedded (FFPE) tissue sections of malignant melanomas. IKH-1 had a high specificity and IKH-2 and 100% specificity to FFPE tissue sections of melanocytic lesions. PMID- 1591224 TI - Presence and interpretation of vascular immune deposits in human skin: the value of direct immunofluorescence. AB - Direct immunofluorescence investigation of the skin is an easy and valuable technique to establish the diagnosis immune complex vasculitis. Vascular immune deposits can be found in 60-80% of all cases. Absence of vascular immune deposits, however, does not exclude vasculitis per se, since the dynamics of the vasculitic process limit their presence in time. Knowledge of these dynamics is indispensable for both the clinician and the interpreter. Several practical options are discussed that may increase sensitivity. The specificity of vascular immune deposits has become a complex matter. Different immunoglobulin classes have different specificity, indicating that specificity also depends on the relative incidence of individual immunoglobulin classes. Some of these relative incidences seem to have changed over the years. Furthermore, several non vasculitic diseases and conditions have now been described, that may show fluorescent pictures similar to vasculitis and thus decrease specificity. PMID- 1591225 TI - Induction of c-fos but not c-myc in S-91 cells by melanization signals. AB - Synthesis of the pigment melanin is a complex differentiated function performed by pigment cells in response to a variety of stimuli. The possible roles of the proto-oncogenes c-fos and c-myc in the control of pigmentation were studied using subconfluent, actively proliferating Cloudman S-91 murine melanoma cells stimulated to synthesize melanin by melanocyte stimulating hormone (MSH) or forskolin. Stimulation caused a significant increase in melanin synthesis when compared to control cells, but had no effect on cell growth. Northern analysis of total cellular RNA demonstrated rapid, transient induction of c-fos mRNA as early as 30 min after stimulation with MSH or forskolin. In contrast, there was no effect on the high constitutive expression of c-myc in these actively proliferating cells. These data strongly suggest that the induction of c-fos mRNA is an early genetic event in stimulation of melanin synthesis and thus this proto oncogene may play a major role in the regulation of this differentiated function, as reported for other forms of cellular differentiation. In contrast, c-myc expression is unaffected and instead correlated with cellular proliferative capacity. These results are consistent with the hypothesis that the down regulation of c-myc frequently observed during cell differentiation is not a necessary event, but rather reflects an associated decrease in cell growth rate. The S-91 melanoma system appears to provide a convenient model for study of the regulation for a single, well defined differentiated function that is independent of growth rate. PMID- 1591226 TI - Subdermal penetration of topically applied clobetasol propionate in ointment base through intact human skin: lack of effect on subcutaneous adipose tissue blood flow. AB - Some data have demonstrated a substantial subdermal accumulation of topically applied drugs in animals. The aim of this study was to evaluate a possible effect of epicutaneously applied clobetasol propionate on blood flow in human subcutaneous adipose tissue. Nine healthy subjects were studied. The 133Xenon wash-out method was used for the measurement of subcutaneous blood flow. Resting blood flow and the local blood flow regulatory mechanisms, autoregulation of blood flow and the veno-arteriolar reflex, were assessed prior to treatment and were measured following 24, 48 and 72 h of treatment. The results demonstrated no effect of clobetasol propionate on resting subcutaneous blood flow or the local regulatory mechanisms. PMID- 1591227 TI - Altered distribution of 1-2B7B antigen in basal cell carcinoma, squamous cell carcinoma and Bowen's disease. AB - Skin lesions of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and Bowen's disease were immunohistochemically examined using the 1-2B7B monoclonal antibody, which recognizes a 120 kDa polypeptide component found in hemidesmosomes of normal human epidermis and hemidesmosome-like adhesion junction of vascular endothelial cells, to disclose altered characteristics of the interface between the tumor cell aggregate and stromal tissues of the epidermal neoplasms. In BCC, 1-2B7B antigen was rarely expressed at the tumor cell aggregate-stromal tissue interface, where poorly developed hemidesmosometonofibril complexes and a normal-looking lamina densa were detectable. In SCC and Bowen's disease, 1-2B7B antigen was expressed not only along the interface of the tumor nest and stromal tissue, but also in the intercellular space of the desmosomes and other adhesion junction structures that lack associating tonofibrils. In the invading front of SCC, 1-2B7B antigen had partly disappeared from the tumor cell aggregate-stromal tissue interface, where neither hemidesmosomes nor lamina densa were noted. The altered distribution of this hemidesmosomal component in the epidermal neoplasms seems to reflect aberrant interaction of neoplasmic cells and surrounding stromal tissue. PMID- 1591228 TI - George Lyman Duff Memorial Lecture. Atherogenesis in diabetes. PMID- 1591229 TI - Early abnormalities in coronary heart disease risk factors in relatives of subjects with non-insulin-dependent diabetes. AB - Coronary heart disease risk factor levels were studied in 184 first-degree relatives (sisters and brothers) of non-insulin-dependent diabetic subjects (124 relatives with normoglycemia, 34 relatives with impaired glucose tolerance [IGT], and 26 relatives with non-insulin-dependent diabetes mellitus [NIDDM]) and in 215 relatives of nondiabetic subjects (194 relatives with normoglycemia and 21 relatives with IGT). Subjects with IGT exhibited the highest insulin responses to an oral glucose load. Systolic blood pressure was significantly higher; serum high density lipoprotein cholesterol level was significantly lower; and total, low density lipoprotein, and very low density lipoprotein triglyceride levels were higher in the relatives with a family history of diabetes who had IGT or NIDDM than in the normoglycemic relatives without a family history of diabetes. These abnormal changes were not seen in normoglycemic relatives or relatives with IGT who had no family history of NIDDM. Thus, in relatives of diabetics, abnormal glucose tolerance seems to induce changes in cardiovascular heart disease risk factor levels that are similar to those observed in NIDDM. Therefore, a family history of diabetes adds substantially to the risk for atherosclerosis, particularly in subjects with IGT. PMID- 1591231 TI - Regional differences in arterial low density lipoprotein metabolism in surgically postmenopausal cynomolgus monkeys. Effects of estrogen and progesterone replacement therapy. AB - To determine if arterial lipoprotein metabolism may be involved in mediating well known anatomic regional differences in susceptibility to atherosclerosis, arterial low density lipoprotein (LDL) metabolism and extent of atherosclerosis were studied in 17 ovariectomized female cynomolgus monkeys. The animals were fed an atherogenic diet for 18 weeks, during which time one group received 17 beta estradiol and cyclic progesterone treatment (n = 9) and the controls received no hormone replacement therapy (n = 8). As reported previously, hormone replacement markedly reduced the accumulation of LDL in coronary arteries without affecting plasma lipoprotein patterns. We report here that LDL metabolism differed among arterial sites. LDL accumulation, LDL degradation rate, and the concentration of undegraded LDL were greatest in the coronary arteries and carotid bifurcations compared with the aorta, iliac arteries, and cerebral arteries. Although hormone replacement decreased indexes of LDL metabolism, there was no effect on intimal thickness or indexes of endothelial injury, such as leukocyte adhesion and endothelial cell turnover rate. There were, however, regional differences in these morphological parameters. The intima was thickest in the aorta, and leukocyte adhesion and endothelial cell turnover rates were greatest in the carotid bifurcation and thoracic aorta. The decreased accumulation and metabolism of LDL caused by hormone replacement therapy was specific to the arterial system and did not occur in the liver or other peripheral tissues. PMID- 1591230 TI - Apolipoprotein B mRNA abundance is decreased by eicosapentaenoic acid in CaCo-2 cells. Effect on the synthesis and secretion of apolipoprotein B. AB - The regulation of apolipoprotein B (apo B) metabolism by eicosapentaenoic acid was investigated in CaCo-2 cells. Cells cultured on semipermeable membranes that separated an upper from a lower well were incubated for 48 hours with albumin alone or 1 mM eicosapentaenoic acid or oleic acid attached to albumin (4:1, mol/mol). Compared with cells incubated with oleic acid, cells incubated with eicosapentaenoic acid synthesized and secreted less [3H]glycerol-labeled triglycerides. Although both fatty acids increased cellular triglyceride mass compared with control cells, less triglycerides accumulated in cells incubated with the n-3 fatty acid. The secretion of triglyceride and apo B mass by cells incubated with eicosapentaenoic acid was less than that observed by cells incubated with oleate. The amount of apo B mass within cells, however, was not altered by either of the fatty acids and was similar to amounts found in control cells. Apo B mRNA abundance was decreased fourfold in cells exposed for 48 hours to eicosapentaenoic acid. In contrast, in cells incubated with oleic acid, apo B mRNA levels were not significantly altered. Pulse-chase experiments were performed to investigate the regulation of apo B synthesis and degradation by the fatty acids. In cells incubated with eicosapentaenoic acid, the synthesis and basolateral secretion of newly synthesized apo B-100 and apo B-48 were significantly less compared with control cells or cells incubated with oleic acid. In contrast, the synthesis and secretion of newly synthesized apo B in cells exposed to oleic acid were similar to control cells. Rates of apo A-I synthesis were similar in cells incubated with either of the fatty acids. Compared with control cells and cells incubated with eicosapentaenoic acid, the residence time of labeled apo B in cells incubated with oleic acid was prolonged. The percentage of newly synthesized apo B that was degraded was less in cells incubated with oleic acid. In contrast, residence times and the percentages of apo A-I and apo B-48 degraded were similar in control cells and cells incubated with the fatty acids. Thus, in CaCo-2 cells, compared with the effects of oleic acid, eicosapentaenoic acid impairs triglyceride transport in part by inhibiting apo B synthesis and secretion. The inhibition of apo B synthesis by eicosapentaenoic acid may be related to a decrease in gene transcription or a decrease in mRNA stability, as apo B mRNA levels were significantly decreased in cells incubated with this fatty acid.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1591232 TI - Delivery of passivating proteins to sutures during passage through the vessel wall reduces subsequent platelet deposition by blocking fibrinogen adsorption. AB - Intraluminal vascular suture material, which attracts fewer than the expected number of platelets compared with the same biomaterial exposed to blood in vitro, differs from the untreated biomaterial in that it has been passed once through the vessel wall. The mechanism by which this apparently trivial maneuver reduces platelet deposition was investigated. Polypropylene suture (7-0 Prolene) was passed through human arteries (fetal and adult), and platelet deposition to the suture was measured in a standardized perfusion chamber. Single vessel passage of the sutures reduced platelet deposition by 68 +/- 23%, which contrasts sharply with the power of prostaglandin E1 (1 microM PGE1 is sufficient to abolish platelet shape change and aggregation), which inhibited only 11% of platelet deposition to the sutures. Aspirin treatment of the vessel (to prevent PGI2 formation) or endothelial stripping (to remove the ability to produce nitric oxide) had no effect on the degree of inhibition. Passage of the suture through a vessel analogue (expanded polytetrafluoroethylene) did not inhibit platelet deposition. 125I-fibrinogen adsorption to the suture after vessel passage was reduced to a degree similar to that of platelet deposition. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of proteins eluted from vessel-passed sutures revealed bands at 66, 47, and 16 kd. Western blotting indicated the presence of large amounts of albumin and hemoglobin, a moderate amount of haptoglobin, and only trace amounts of fibrinogen. When sutures were exposed to each of these proteins in vitro before perfusion, albumin and hemoglobin were found to reproduce the effect of vessel passage alone on platelet deposition. We conclude that albumin and hemoglobin adsorb to sutures during their passage through the vessel subendothelium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591233 TI - The role of cholesteryl ester transfer protein in primate apolipoprotein A-I metabolism. Insights from studies with transgenic mice. AB - To assess the effects of cholesteryl ester transfer protein (CETP) on the primate lipoprotein profile, a transgenic mouse expressing cynomolgus monkey CETP was developed. The C57BL/6 mouse was used, and four lines expressing the primate CETP were established. The level of CETP activity in the plasma of the transgenic mice ranged from values similar to those obtained for the monkey to levels approximately sixfold higher than that in the normal monkey. When all of the lines were taken into consideration, there was a strong (r = -0.81 or higher, p less than 0.01) negative correlation between plasma CETP activity and total plasma cholesterol, plasma apolipoprotein (apo) A-I levels, and plasma apo A-I to apo B ratio. There was a strong positive correlation (r = 0.77) between plasma CETP activity and plasma apo B levels. The size of the apo A-I-containing lipoproteins was significantly reduced in mice with high plasma CETP activity, and that reduction in size was due to the absence of the larger (HDL1 and HDL2) apo A-I-containing particles in the plasma. When the transgenic mice were fed a high-fat, high-cholesterol diet, the effects of the diet on lipoprotein profile were more prominent in the CETP transgenic mice than the controls. The CETP transgenic mice had, for example, substantially higher plasma cholesterol and plasma apo B levels (p less than 0.01), and the apo B-containing lipoproteins were generally larger than those in the nontransgenic C57BL/6 mice consuming the same diet.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591234 TI - Increased susceptibility to activation and increased uptake of low density lipoprotein by cholesterol-loaded macrophages. AB - Inflammation is associated with macrophage activation, and this process has been shown to occur during atherogenesis. Macrophages (J774A.1) that were activated with either lipopolysaccharide (LPS), zymosan, or phorbol ester demonstrated a 30 35% increased uptake and degradation of low density lipoprotein (LDL) in comparison with nonactivated cells. This phenomenon was also shown for LDL cellular binding, and it resulted in macrophage cholesterol accumulation, as evidenced by cholesterol mass determination and flow cell cytometric analysis. Enhanced uptake of LDL was also obtained with two other types of macrophages: mouse peritoneal macrophages and human monocyte-derived macrophages. In LPS stimulated macrophages, high density lipoprotein-mediated cholesterol efflux was not different from that shown in nonstimulated cells. Cellular cholesterol synthesis, however, was increased by 25% in the activated macrophages. Macrophage activation, measured as cellular procoagulant activity, was higher in cholesterol loaded than in nonloaded cells. On stimulation of cholesterol-loaded macrophages, cellular uptake and degradation of LDL were increased by 3.3-fold in comparison with nonactivated cholesterol-loaded cells. Human monocyte-derived macrophages from hypercholesterolemic patients were found to contain 52% more cholesterol mass than macrophages derived from normal healthy donors. These cells demonstrated increased activation (twofold) in response to LPS stimulation and also showed 25% enhanced cellular degradation of LDL. We conclude that activation of macrophages during atherogenesis can lead to foam cell formation, and this mechanism is probably operative in hypercholesterolemic patients. PMID- 1591235 TI - Bile acid biosynthesis. AB - To conclude, the last several years have seen a resurgence of interest in the biosynthesis of bile acids. This focus has come about due to the central roles that these molecules play in cholesterol and fat metabolism and due to recent advances in their chemistry, biochemistry, and molecular biology. The application of probes generated by these methodologies has begun to generate novel insight into bile acid metabolism, regulation, and genetics. The next several years should be equally exciting. PMID- 1591236 TI - Detection and characterization of an early folding intermediate of T4 lysozyme using pulsed hydrogen exchange and two-dimensional NMR. AB - Two-dimensional 1H-15N NMR techniques combined with pulsed hydrogen-deuterium exchange have been used to characterize the folding pathway of T4 lysozyme. In the unfolded state, there is little differential protection of the various amides from hydrogen exchange. In the native folded structure, 84 amides of the 164 residues are sufficiently spectrally resolved and protected from solvent exchange to serve as probes of the folding pathway. These probes are located in both the N terminal and C-terminal domains of the native folded structure of the protein. The studies described here show that at least one intermediate is formed early during refolding at low denaturant concentrations. This intermediate (or intermediates) forms very rapidly (within the 10-ms temporal resolution of our mixing device) under the conditions used and is completed at least 10 times faster than the overall folding event. The intermediate(s) protect(s) from exchange a subset of amides in the N-terminal and C-terminal regions of the protein. In the final folded states these protected regions correspond to two alpha-helices and a beta-sheet region. These amides are protected from exchange by factors between 20 and 200 as compared to the fully unfolded protein. Protection of this magnitude is consistent with the formation of somewhat exposed secondary structure in these regions and could represent a "molten globule"-like or a "framework"-like structure for the intermediate(s) in which specific parts of the sequence form isolated secondary structures that are not stabilized by extensive tertiary interactions. PMID- 1591237 TI - Spontaneous formation of helical structures from phospholipid-nucleoside conjugates. AB - Phospholipid-nucleoside conjugates containing two myristoyl groups and a nucleotidyl group, collectively designated as dimyristoyl-5' phosphatidylnucleosides, were enzymatically synthesized and their self organization, morphology, and physicochemical properties investigated. The dimyristoyl-5'-phosphatidylnucleosides spontaneously assembled to form various types of helical strands. Neutral and alkaline solutions of dimyristoyl-5' phosphatidyladenosine (DMPA) produced multihelical strands. The multihelical strand consisted of several single helical strands of approximately 50 A in diameter and helical pitch approximately 100 A. DMPA produced cigar-like scrolls (tubular structures) in acidic solution, which consisted of many double-helical strands aligned parallel to each other. Diacyl-5'-phosphatidyladenosine with a shorter chain length as long as an alkyl group, dilauroyl-5' phosphatidyladenosine (DLPA), didecanoyl-5'-phosphatidyladenosine (DDPA), and dioctanoyl-5'-phosphatidyladenosine (DOPA) formed extended tape structures having double-helical strands aligned parallel. Dimyristoyl-5'-phosphatidylcytidine (DMPC) produced network structures at an early stage, which were slowly transformed into multihelical strands. The multihelical strands contained some single-helical strands of approximately 55 A in diameter and helical pitch approximately 150 A. DMPA produced no definite helical structure in acidic solution but rather large lamellar structures. Dimyristoyl-5'-phosphatidyluridine (DMPU) produced crystalline platelet structures of approximately 1000 A in width in both alkaline and acidic solution. A 1:1 mixture of DMPA and DMPU formed a new hybrid helical strand having a wide and thick ribbon structure of approximately 300 A in diameter and helical pitch approximately 2000 A. The formation of different helical strands and effects of chain lengths of alkyl groups and a nucleotidyl group in phospholipid-nucleoside conjugates on that of helical strands in aqueous solution are discussed. PMID- 1591238 TI - Mambin, a potent glycoprotein IIb-IIIa antagonist and platelet aggregation inhibitor structurally related to the short neurotoxins. AB - The purification, complete amino acid sequence, functional activity, and structural modeling are described for mambin, a platelet glycoprotein GP IIb-IIIa antagonist and potent inhibitor of platelet aggregation from the venom of the Elapidae snake Dendroaspis jamesonii (Jameson's mamba). Mambin is 59 residues in length and contains four disulfide linkages and an RGD amino acid sequence found in protein ligands that bind to GP IIb-IIIa. Mambin inhibits ADP-induced platelet aggregation (IC50 = 172 +/- 22 nM) and inhibits the binding of purified platelet fibrinogen receptor GP IIb-IIIa to immobilized fibrinogen (IC50 = 3.1 +/- 0.8 nM). Mambin has very little sequence similarity to the Viperidae family of platelet aggregation inhibitors, except for the RGD-containing region in the protein. However, mambin does have ca. 47% similarity to the short-chain postsynaptic neurotoxins found in other Elapidae venoms, which do not contain the RGD sequence and do not act as GP IIb-IIIa antagonists. On the basis of its circular dichroism spectrum, mambin has a beta-sheet structure characteristic of the neurotoxins. Molecular modeling of the mambin sequence onto the erabutoxin b structure predicts a very similar structure within the entire protein except for the loop containing the RGD sequence. Mambin may therefore represent a genetic hybrid of neurotoxic and hemotoxic proteins found in snake venoms. PMID- 1591239 TI - Characterization of actin- and lipid-binding domains in severin, a Ca(2+) dependent F-actin fragmenting protein. AB - Severin is a Ca(2+)-activated actin-binding protein that nucleates actin assembly and severs and caps the fast growing ends of actin filaments. It consists of three highly conserved domains. To investigate the domain structure of severin, we constructed genetically the N-terminal domain 1, the middle domain 2, and the tandem domains 2 + 3. Their interaction with actin, Ca2+, and lipids was characterized. Domain 1 contains the F-actin capping and a Ca(2+)-binding site [Eichinger, L., Noegel, A. A., & Schleicher, M. (1991) J. Cell Biol. 112, 665 676]. Binding of domain 2 to actin filaments was Ca(2+)-dependent and saturated at a 1:1 molar ratio. In the presence of Ca2+, about 1.5 mol of domains 2 + 3 bound per mole of F-actin subunit. Scatchard analysis gave a Kd of 18 microM for the interaction of domain 2 with F-actin subunits and a Kd of 1.6 microM for domains 2 + 3. Low-shear viscometry, electron microscopy, and low-speed sedimentation assays showed that domains 2 + 3 induced bundling of actin filaments. The influence of PIP2 micelles on the different activities of severin was assayed using native severin and N- and C-terminally truncated fragments. Severin contains at least two PIP2-binding sites since the activities of the two nonoverlapping severin fragments domain 1 and domains 2 + 3 were inhibited by PIP2. The specificity of severin-phospholipid interaction was investigated by studying the regulation of native severin by PIP2 and other pure or mixed phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591240 TI - Kinetic and modeling studies of S3-S3' subsites of HIV proteinases. AB - Kinetic analysis and modeling studies of HIV-1 and HIV-2 proteinases were carried out using the oligopeptide substrate [formula: see text] and its analogs containing single amino acid substitutions in P3-P3' positions. The two proteinases acted similarly on the substrates except those having certain hydrophobic amino acids at P2, P1, P2', and P3' positions (Ala, Leu, Met, Phe). Various amino acids seemed to be acceptable at P3 and P3' positions, while the P2 and P2' positions seemed to be more restrictive. Polar uncharged residues resulted in relatively good binding at P3 and P2 positions, while at P2' and P3' positions they gave very high Km values, indicating substantial differences in the respective S and S' subsites of the enzyme. Lys prevented substrate hydrolysis at any of the P2-P2' positions. The large differences for subsite preference at P2 and P2' positions seem to be at least partially due to the different internal interactions of P2 residue with P1', and P2' residue with P1. As expected on the basis of amino acid frequency in the naturally occurring cleavage sites, hydrophobic residues at P1 position resulted in cleavable peptides, while polar and beta-branched amino acids prevented hydrolysis. On the other hand, changing the P1' Pro to other amino acids prevented substrate hydrolysis, even if the substituted amino acid had produced a good substrate in other oligopeptides representing naturally occurring cleavage sites. The results suggest that the subsite specificity of the HIV proteinases may strongly depend on the sequence context of the substrate. PMID- 1591241 TI - Site-directed mutagenesis and deletion of the carboxyl terminus of Escherichia coli ribonucleotide reductase protein R2. Effects on catalytic activity and subunit interaction. AB - Ribonucleotide reductase from Escherichia coli consists of two dissociable, nonidentical homodimeric proteins called R1 and R2. The role of the C-terminal region of R2 in forming the R1R2 active complex has been studied. A heterodimeric R2 form with a full-length polypeptide chain and a truncated one missing the last 30 carboxyl-terminal residues was engineered by site-directed mutagenesis. Kinetic analysis of the binding of this protein to R1, compared with full-length or truncated homodimer, revealed that the C-terminal end of R2 accounts for all of its interactions with R1. The intrinsic dissociation constant of the heterodimeric R2 form, with only one contact to R1, 13 microM, is of the same magnitude as that obtained previously [Climent, I., Sjoberg, B.-M., & Huang, C. Y. (1991) Biochemistry 30, 5164-5171] for synthetic C-terminal peptides, 15-18 microM. We have also mutagenized the only two invariant residues localized at the C-terminal region of R2, glutamic acid-350 and tyrosine-356, to alanine. The binding of these mutant proteins to R1 remains tight, but their catalytic activity is severely affected. While E350A protein exhibits a low (240 times less active than the wild-type) but definitive activity, Y356A is completely inactive. A catalytic rather than structural role for these residues is discussed. PMID- 1591242 TI - A site-directed mutagenesis study to identify amino acid residues involved in the catalytic function of the restriction endonuclease EcoRV. AB - We have used site-directed mutagenesis of the EcoRV restriction endonuclease to change amino acid side chains that have been shown crystallographically to be in close proximity to the scissile phosphodiester bond of the DNA substrate. DNA cleavage assays of the resulting mutant proteins indicate that the largest effects on nucleolytic activity result from substitution of Asp74, Asp90, and Lys92. We suggest on the basis of structural information, mutagenesis data, and analogies with other nucleases that Asp74 and Asp90 might be involved in Mg2+ binding and/or catalysis and that Lys92 probably stabilizes the pentacovalent phosphorus in the transition state. These amino acids are part of a sequence motif, Pro-Asp...Asp/Glu-X-Lys, which is also present in EcoRI. In both enzymes, it is located in a structurally similar context near the scissile phosphodiester bond. A preliminary mutational analysis with EcoRI indicates that this sequence motif is of similar functional importance for EcoRI and EcoRV. On the basis of these results, a proposal is made for the mechanism of DNA cleavage by EcoRV and EcoRI. PMID- 1591243 TI - Construction of a cDNA for the human c-fes protooncogene protein-tyrosine kinase and its expression in a baculovirus system. AB - Previous studies have established that the 93-kDa protein-tyrosine kinase (PTK) encoded by the human c-fes protooncogene plays an active role in the induction of terminal myeloid differentiation. However, this enzyme is expressed at very low levels in myeloid cells, making isolation of sufficient quantities for detailed biochemical analysis difficult. To overcome this problem, we used the polymerase chain reaction to construct a full-length c-fes cDNA from overlapping 5' and 3' partial cDNA sequences. The c-fes cDNA was expressed at high levels in a baculovirus system, and the catalytically active recombinant c-fes gene product p93c-fes was partially purified by DEAE-Sepharose and tyrosine-agarose chromatography. Recombinant p93c-fes was indistinguishable from the native protein in terms of its apparent molecular weight following SDS-PAGE, catalytic activity, Km for poly(Glu,Tyr)4:1, antigenicity, and phosphopeptide pattern generated with Staphylococcus aureus protease. PMID- 1591244 TI - Structure of a G.T.A triplet in an intramolecular DNA triplex. AB - A 32-base DNA oligonucleotide has been studied by one- and two-dimensional 1H NMR spectroscopy and is shown to form a stable, pyr.pur.pyr, intramolecular triple helical structure, with a four C loop and a TATA loop connecting the Watson-Crick and Hoogsteen-paired strands, respectively. This triplex contains five T.A.T base triplets, two C+.G.C base triplets, and an unusual G.T.A base triplet which disrupts the pyr.pur.pyr motif. The G.T.A triplet consists of a Watson-Crick T.A base pair, with the T situated in the "purine strand" and the A situated in the "pyrimidine strand" and a G situated in the Hoogsteen-base-paired "pyrimidine strand" hydrogen bonded to the T. The base-pairing structure of the G.T.A triplet has been investigated and has been found to involve a single hydrogen bond from the guanine amino group to the O4 carbonyl of the thymine, leaving the guanine imino proton free. The specific amino proton involved in the hydrogen bond is the H2(2) proton. This orients the guanine such that its sugar is near the thymine methyl group. The guanine sugar adopts an N-type (C3'-endo) sugar pucker in this triplet. The stability of the G.T.A triplet within pyr.pur.pyr triplexes is discussed. PMID- 1591245 TI - Fluorescence resonance energy transfer analysis of the structure of the four-way DNA junction. AB - We have carried out fluorescence resonance energy transfer (FRET) measurements on four-way DNA junctions in order to analyze the global structure and its dependence on the concentration of several types of ions. A knowledge of the structure and its sensitivity to the solution environment is important for a full understanding of recombination events in DNA. The stereochemical arrangement of the four DNA helices that make up the four-way junction was established by a global comparison of the efficiency of FRET between donor and acceptor molecules attached pairwise in all possible permutations to the 5' termini of the duplex arms of the four-way structure. The conclusions are based upon a comparison between a series of many identical DNA molecules which have been labeled on different positions, rather than a determination of a few absolute distances. Details of the FRET analysis are presented; features of the analysis with particular relevance to DNA structures are emphasized. Three methods were employed to determine the efficiency of FRET: (1) enhancement of the acceptor fluorescence, (2) decrease of the donor quantum yield, and (3) shortening of the donor fluorescence lifetime. The FRET results indicate that the arms of the four way junction are arranged in an antiparallel stacked X-structure when salt is added to the solution. The ion-related conformational change upon addition of salt to a solution originally at low ionic strength progresses in a continuous noncooperative manner as the ionic strength of the solution increases. The mode of ion interaction at the strand exchange site of the junction is discussed. PMID- 1591246 TI - Backbone dynamics of calcium-loaded calbindin D9k studied by two-dimensional proton-detected 15N NMR spectroscopy. AB - Backbone dynamics of calcium-loaded calbindin D9k have been investigated by two dimensional proton-detected heteronuclear nuclear magnetic resonance spectroscopy, using a uniformly 15N enriched protein sample. Spin-lattice relaxation rate constants, spin-spin relaxation rate constants, and steady-state [1H]-15N nuclear Overhauser effects were determined for 71 of the 72 backbone amide 15N nuclei. The relaxation parameters were analyzed using a model-free formalism that incorporates the overall rotational correlation time of the molecule, and a generalized order parameter (S2) and an effective internal correlation time for each amide group. Calbindin D9k contains two helix-loop helix motifs joined by a linker loop at one end of the protein and a beta-type interaction between the two calcium-binding loops at the other end. The amplitude of motions for the calcium-binding loops and the helices are similar, as judged from the average S2 values of 0.83 +/- 0.05 and 0.85 +/- 0.04, respectively. The linker region joining the two calcium-binding subdomains of the molecule has a significantly higher flexibility, as indicated by a substantially lower average S2 value of 0.59 +/- 0.23. For residues in the linker loop and at the C-terminus, the order parameter is further decomposed into separate order parameters for motional processes on two distinct time scales. The effective correlation times are significantly longer for helices I and IV than for helices II and III or for the calcium-binding loops. Residue by residue comparisons reveal correlations of the order parameters with both the crystallographic B-factors and amide proton exchange rates, despite vast differences in the time scales to which these properties are sensitive. The order parameters are also utilized to distinguish regions of the NMR-derived three-dimensional structure of calbindin D9k that are poorly defined due to inherently high flexibility, from poorly defined regions with average flexibility but a low density of structural constraints. PMID- 1591247 TI - Thermodynamics of ribonuclease T1 denaturation. AB - Differential scanning calorimetry has been used to investigate the thermodynamics of denaturation of ribonuclease T1 as a function of pH over the pH range 2-10, and as a function of NaCl and MgCl2 concentration. At pH 7 in 30 mM PIPES buffer, the thermodynamic parameters are as follows: melting temperature, T1/2 = 48.9 +/- 0.1 degrees C; enthalpy change, delta H = 95.5 +/- 0.9 kcal mol-1; heat capacity change, delta Cp = 1.59 kcal mol-1 K-1; free energy change at 25 degrees C, delta G degrees (25 degrees C) = 5.6 kcal mol-1. Both T1/2 = 56.5 degrees C and delta H = 106.1 kcal mol-1 are maximal near pH 5. The conformational stability of ribonuclease T1 is increased by 3.0 kcal/mol in the presence of 0.6 M NaCl or 0.3 M MgCl2. This stabilization results mainly from the preferential binding of cations to the folded conformation of the protein. The estimates of the conformational stability of ribonuclease T1 from differential scanning calorimetry are shown to be in remarkably good agreement with estimates derived from an analysis of urea denaturation curves. PMID- 1591248 TI - Identification of the three-dimensional thioredoxin motif: related structure in the ORF3 protein of the Staphylococcus aureus mer operon. AB - We have developed a computerized search pattern for recognition of the three dimensional redox site of thioredoxins based on primary and predicted secondary structure. This pattern, developed in the ARIADNE protein expert system, is used to search for thioredoxin-like tertiary structural motif among proteins for which the only structural information is the primary sequence. The pattern was trained on 102 protein sequences (25 functionals and 77 controls); it matches all 25 members of the functional set under cutoff conditions that include only 2 members of the control set, for a sensitivity of 1.0 and a specificity of 0.97. The pattern matches only one of the two thioredoxin-like domains in protein disulfide isomerases (PDIs) and their analogues, suggesting that the C-terminal domain is more structurally similar to thioredoxin than the N-terminal domain. The Escherichia coli DsbA protein, a possible PDI analogue, appears to be more structurally similar to the N-terminal thioredoxin-like domain of PDIs. Thioredoxin-like redox functionality has been proposed for lutropin and follitropin, in part on the basis of their having -Cys-X-Pro-Cys- sequences. None match our pattern; all lack a predicted alpha-helix pattern element immediately after the active site. Hypothetical proteins in the National Biomedical Research Foundation Protein Identification Resource database were searched for matches to the pattern. The most interesting match was a hypothetical protein (161 residues) from the third open reading frame in the Staphylococcus aureus mer operon, which is involved in mercury detoxification. The match to our pattern and the hydrophobicity distribution in aligned elements of secondary structure not in our pattern strongly suggest that it has thioredoxin-like structure. PMID- 1591249 TI - Structure of the active site of lignin peroxidase isozyme H2: native enzyme, compound III, and reduced form. AB - The wood-degrading fungus Phanerochaete chrysosporium secretes a number of extracellular enzymes called lignin peroxidases which are involved in the degradation of both lignin and a number of persistent environmental pollutants. Lignin peroxidase isozyme H2, a glycosylated protein of approximately 40 kDa, contains a single heme. X-ray absorption spectroscopy (XAS) has been used to probe the local environment of the iron in the active site of resting enzyme, reduced enzyme, and compound III. For the native and reduced forms, respectively, the average Fe-pyrrole nitrogen distances are 2.055 and 2.02 A (+/- 0.015 A); the Fe-proximal nitrogen distance is 1.93 and 1.91 A (+/- 0.02 A) while the Fe-distal ligand distance is 2.17 and 2.10 A (+/- 0.03 A). Although the results are not as well-defined, the active-site structure of compound III is largely 2.02 +/- 0.015 A for the average Fe-pyrrole nitrogen distance, 1.90 +/- 0.02 for the Fe-proximal nitrogen, and 1.74 +/- 0.03 A for the Fe-distal ligand distance. The heme iron pyrrole nitrogen distance is more expanded in ligninase H2 than in other peroxidases. The possible significance of this is discussed in relation to other heme proteins. PMID- 1591250 TI - A test of the linear extrapolation of unfolding free energy changes over an extended denaturant concentration range. AB - Guanidine hydrochloride (GdnHCl) and thermally induced unfolding measurements on the oxidized form of Escherichia coli thioredoxin at pH 7 were combined for the purpose of assessing the functional dependence of unfolding free energy changes on denaturant concentration over an extended GdnHCl concentration range. Conventional analysis of GdnHCl unfolding exhibits a linear plot of unfolding delta G vs [GdnHCl] in the transition zone. In order to extend unfolding delta G measurements outside of that narrow concentration range, thermal unfolding measurements were performed using differential scanning calorimetry (DSC) in the presence of low to moderate concentrations of GdnHCl. The unfolding delta G values from the DSC measurements were corrected to 25 degrees C using the Gibbs Helmholtz equation and mapped onto the delta G vs [GdnHCl] plot. The dependence of unfolding delta G on [GdnHCl] was found to be linear over the full denaturant concentration range, provided that the chloride ion concentration was kept at a threshold of greater than or equal to 1.5 M. In the DSC experiments performed in the presence of GdnHCl, chloride concentrations were maintained at 1.5 M by addition of appropriate amounts of NaCl. The linear extrapolation method (LEM) gives an unfolding free energy change in the absence of denaturant (delta G degrees N-U) in excellent agreement with the delta G determined by DSC measurement in 1.5 M NaCl. The various methods give a consensus unfolding delta G value of 8.0 kcal/mol at 25 degrees C in the absence of denaturant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591251 TI - Pierre Robin: a personal diary. AB - This personal diary of the birth and subsequent management of a child with Robin sequence secondary to Stickler syndrome is written by a mother who also has Stickler syndrome. Her discussion of the case illustrates the importance of reaching a primary diagnosis in order to deliver good patient care. PMID- 1591252 TI - The implications of the diagnosis of Robin sequence. AB - "Pierre Robin" is one of the most readily recognized diagnostic eponyms in medicine, yet it is a poorly understood nonspecific grouping of malformations that has no prognostic significance. Although the science of dysmorphology and in particular those who study children with clefts would be reluctant to forego the use of this diagnosis, the reality is that fewer than 20 percent of children with micrognathia and cleft palate should have this term applied. The syndromic diagnoses of 100 children with Robin sequence are presented and discussed in relation to morphologic characteristics. Upper airway obstruction and its relationship to feeding problems is also discussed. PMID- 1591253 TI - Comparison of the craniofacial characteristics of two syndromes associated with the Pierre Robin sequence. AB - The craniofacial characteristics of two syndromes commonly associated with Robin sequence were compared for 49 subjects. Lateral cephalograms were analyzed for four groupings: Group I--Stickler syndrome with versus without Robin, Group II- velocardiofacial (VCF) syndrome with versus without Robin, Group III--Stickler without Robin compared to VCF without Robin, and Group IV--Stickler with Robin compared to VCF with Robin. Thirty-two skeletal and 18 soft tissue measurements were compared. In Group I, three skeletal measurements were significantly different (SNA, SNB, and SNPg). In Group II, no significant difference was found for any of the 50 measurements. In Group III, a significant difference was demonstrated for seven parameters (one skeletal, six pharyngeal and airway). In Group IV, two skeletal and eight airway measures were significantly different. The findings indicate that the relative maxillary and mandibular retrognathia observed in Stickler/Robin patients may predispose them to the Robin sequence and vice versa; the Robin features in VCF may be caused by hypotonia rather than any craniofacial or physical obstruction of the airway; Stickler and VCF are similar in craniofacial morphology but show marked differences in pharyngeal and airway morphology; and cephalometrics should not be the sole prognosticator of the Robin sequence and its association with Stickler and VCF. PMID- 1591254 TI - Pediatric management of Robin sequence. AB - The care of infants with Robin sequence is discussed with special reference to upper airway obstruction and feeding difficulties. The use of nasopharyngeal tubes is recommended initially to alleviate the immediate consequences of hypoxia. Modifications in feeding procedures are minor and involve enlarging the hole in the nipple and keeping the nipple and infant positioned appropriately. PMID- 1591255 TI - Mechanisms of airway obstruction in Robin sequence: implications for treatment. AB - Though the problems associated with Robin sequence may be numerous, especially if the primary cause of the sequence is a multiple anomaly syndrome, the most acute problems in affected newborns is upper airway obstruction. Until recently it has been tacitly assumed that glossoptosis is always the cause of the airway obstruction. More recent evidence has shown that the sources of airway obstruction are multiple and the cause of apnea heterogeneous. The purpose of this paper is to report the mechanisms of upper airway obstruction in 53 infants with Robin sequence. The use of flexible fiber optic endoscopy to specify treatment is discussed in detail. PMID- 1591256 TI - Glossopexy for upper airway obstruction in Robin sequence. AB - A modified glossopexy is described with results of the operation in 24 patients who were specifically selected based on nasopharyngoscopic examination of the upper airway. Only patients with documented glossoptosis on endoscopy were selected for glossopexy. The procedure is designed to use two points of attachment for the tongue, one at the mandibular alveolus and the other at the lower lip. The genioglossus is also released to lengthen the tongue. All patients had resolution of their upper airway obstruction. There was only one partial dehiscence. The glossopexies were all released at the time of palate repair, usually before the first birthday. PMID- 1591257 TI - Effect of glossopexy on speech sound production in Robin sequence. AB - The management of Robin sequence may include glossopexy, in which the tongue is attached to the lower lip and mandible for anterior lingual positioning to resolve upper airway obstruction. The procedure is performed early in infancy and reversed at the time of palatal repair near 1 year of age. This period is critical to prespeech vocalization. The effect of glossopexy on speech sound production was investigated in 17 children with Robin sequence who had glossopexies. Analysis suggested that glossopexy may temporarily affect the development of prespeech skills and sound production. The onset of babbling and initiation of first words was often delayed in the subjects in comparison with syndrome-matched children who had not undergone glossopexy. Tongue-tip sounds were often produced with the tongue blade, but production was perceptually normal. The early delays were temporary and the only long-term effect of glossopexy was a tendency to produce tongue-tip sounds with the tongue blade. PMID- 1591258 TI - Robin sequence: changes in thinking leading to changes in patient care. AB - Robin sequence is now understood to be a grouping of clinical findings that does not represent a distinct multiple anomaly syndrome. Previously known as the "Pierre Robin syndrome," this fairly common association of micrognathia with cleft palate and upper airway obstruction was initially thought to be a specific disease, and entire treatment regimens were established to deal with presumed problems. Until recently, the management of Robin has not been excellent and mortality has been high. It is only a better understanding of the basic mechanisms leading to this sequence that has resulted in better care. This article reviews the history of the delineation of Robin sequence and how the perception of Robin has led directly to management decisions. PMID- 1591259 TI - Evaluation of the sphincter pharyngoplasty. AB - The results of the sphincter pharyngoplasty were evaluated in 139 patients with velopharyngeal incompetence (VPI) who demonstrated active velar elevation. All patients underwent perceptual speech evaluation and lateral phonation radiographic study; select patients underwent multiview videofluoroscopic, flexible nasendoscopic, and pressure-flow studies. All but one patient demonstrated improvement and 109/139 (78.42%) demonstrated resolution of VPI. Sixteen of thirty failed pharyngoplasties were revised. Revision was successful in 8/16 patients yielding an overall success rate of 117/139 (84.17%). Success rate was 67.65 percent for patients managed during the first 5 years and improved to 84.78 percent for patients managed during the last 5 years of this 15-year series. Analysis revealed that younger patients were treated more successfully than older patients, large velopharyngeal areas were treated as successfully as smaller ones, and circular closure patterns were treated more successfully than coronal patterns. The primary cause of failure was insertion of the flap below the point of attempted velopharyngeal contact. PMID- 1591260 TI - Habilitation of patients with clefts: parent and child ratings of satisfaction with appearance and speech. AB - This study examined ratings regarding satisfaction with facial appearance and speech performance from 495 parent-child pairs. Data were obtained from school aged children (5-18 years old) and their parents using standardized independent interviews. Results revealed that 54 percent of the children with cleft lip (CL) or cleft lip and palate (CLP) were very pleased with their appearance, and 62 percent of the cleft palate or CLP subjects were very pleased with speech. Low, but statistically significant correlations exist between the female subjects and their parents in satisfaction with appearance. Although older cleft lip and/or palate patients reported increased satisfaction with speech, no age differences in patient satisfaction with appearance were observed in subjects with CL/CLP. Parents of females expressed more concern about their daughters' appearance than parents of males, while parents of males were more concerned about speech. Implications for craniofacial habilitation teams and research suggestions are discussed. PMID- 1591261 TI - Effects of pubertal changes on the speech of persons with cleft palate. AB - The effects of puberty on the speech of persons with cleft palate and normal to moderate degrees of resonance distortion were investigated. Listeners were rated for resonance, articulation, and speech acceptability from recordings made prepuberty and postpuberty for 18 males who received no surgery during the time they went through puberty. Results suggest that changes were minimal and did not always result in speech improvement or deterioration. PMID- 1591262 TI - Medical students' knowledge of and exposure to cleft palate. AB - To compare the knowledge and experience of medical students in 1989 with that of those surveyed in 1973, a questionnaire about the various aspects of cleft palate was completed by 209 medical students from West Virginia University and the Louisiana State University Medical Center at Shreveport and New Orleans. Results revealed that 1989 students were more familiar with the embryology of cleft palate, racial and gender differences, and intellectual and psychologic issues (p less than .05). In contrast, the 1973 students were more able to define cleft palate, submucous cleft palate, and pharyngeal flap. There was no difference between the two groups of students in the amount of clinical exposure to cleft palate. These findings support the need for greater emphasis on cleft palate at the pre- and postdoctoral levels, as well as within continuing education programs. As part of current programs, the standard of practice of multidisciplinary team management for an individual with cleft palate should be underscored. PMID- 1591263 TI - Natal teeth in monozygotic twins with Van der Woude syndrome. AB - The second monozygotic twin pair concordant for Van der Woude syndrome is reported. Clinical manifestations of this autosomal dominant clefting syndrome included bilateral lower lip pits, cleft lip, and cleft palate. Both sibs were found to have a natal tooth. No other cases of Van der Woude syndrome with this feature have been described previously. It is uncertain whether the presence of a natal tooth in this instance represents a low-frequency association of this disorder. However, it appears more likely that its occurrence was incidental, since natal teeth have been reported before in twin pairs as an isolated finding. PMID- 1591264 TI - Nasopharyngeal characteristics in children with cleft lip and palate. AB - Cephalometric assessment of the nasopharynx and its adjacent structures was carried out in two experimental groups of 5-year-old male patients with unilateral cleft lip and palate. The first group included individuals who had not had surgery, and the second was comprised of individuals who were at least 1 year postpalatoplasty with primary pharyngeal flap. They were compared with a control group of boys of comparable average age who did not have clefts. Both groups of patients with clefts showed a reduction of the nasopharyngeal bony framework related to the posterior position and decreased posterior height of the maxilla without hypertrophy of the adenoids. The smaller nasopharyngeal airway was consistent with the reduction of the size of the bony nasopharynx. There was shortening of the anterior cranial base located in the region of the middle cranial fossa. The height of the body of the sphenoid bone was reduced, but the angle of the cranial base was within normal limits. PMID- 1591265 TI - Prevalence and severity of malocclusion in children with cleft lip and/or palate in Hong Kong. AB - The prevalence and severity of malocclusion among children with cleft lip and palate in Hong Kong has never been assessed or documented. A group of 20 children in the primary or early mixed dentition stages, with clefts of the lip and/or palate were assessed using the Occlusal Index. Results of this preliminary study showed that 92.3 percent of the male and 71.5 percent of the female subjects had severe malocclusion, which implied that comprehensive orthodontic treatment at a later stage would be needed. More than half (69.2% of the male, and 57.1% of the female subjects) had syndrome F, defined as mesial molar relationship, overjet, overbite, posterior crossbite, midline diastema, and midline deviation (Summers, 1966). Therefore malocclusion problems were shown to manifest early in patients with cleft lip and/or palate, and further that it is possible to assess malocclusion prevalence and severity in early stages of dental development. PMID- 1591266 TI - Activation of in situ glycolytic flux by bisphosphorylated compounds: studies in porous rat adipocytes. AB - By carefully permeabilizing eukaryotic cells such that intracellular enzymes are largely retained, an opportunity is created to explore the regulation of in situ flux. This is particularly important since the latter may not be accurately represented by kinetic measurements of isolated, solubilized enzymes from disrupted cells. In this study the action of fructose 2,6-diphosphate (F2,6DP) and other bisphosphorylated sugars which purportedly activate phosphofructokinase 1 (PFK-1; EC 2.7.1.11) were studied. Using porous adipocytcs and initiating flux with radiolabeled glucose 6-phosphate, the regulation of lactate production under both 0.1 and 1.0 mM ATP conditions by F2,6DP, glucose 1,6-diphosphate (G1,6DP), ribulose 1,5-diphosphate (R1,5DP), 2,3 diphosphoglycerate (2,3DPG), and mannose 6 phosphate (M6P) was examined. Studied at 1, 5, and 25 microM concentrations, F2,6DP and 2,3DPG significantly (and to the same extent) augmented glycolysis compared to control (at 0.1 mM ATP, the respective glycolytic rates--as % above control--at these three above-mentioned concentrations for F2,6DP were 60, 84, and 77%, whereas for 2,3DPG they were 84, 105, and 179%; at 1 mM ATP, the F2,6DP effect was 88, 99, and 121%, and for 2,3DPG it was 52, 89, and 96%). Stimulation by these compounds was less obvious at higher glycolytic flux rates (saturating amounts of G6P). Amongst this group, and only at 1.0 mM ATP, the sole other positive effector was 25 microM R1,5DP. The measured fat cell content of G1,6DP was 24 +/- 4 microM (n = 3); at this concentration no significant effect on glycolysis was observed. Examining the effects of 2,3DPG (25 microM) on proximal glycolysis (to triose phosphates) revealed there was a modest, but significant, 41% increase over basal; in contrast, under the exact same conditions, F2,6DP caused a 123% increase. Separate experiments also examined the effect of F2,6DP, 2,3DPG, and G1,6DP on glycolysis at 5 and 25 microM in the presence of a physiologic cytosolic ATP/ADP ratio and free cation concentrations. Under these conditions, F2,6DP and 2,3DPG remained pre-eminent in their stimulatory prowess, inducing 27-71% increases over control, while G1,6DP remained ineffectual. These studies support a locus of action of 2,3DPG on overall glycolysis which is distal to the triose phosphates. M6P was ineffective at all concentrations. In conclusion, F2,6DP is the pre-eminent in situ regulator of in situ adipocyte glycolysis, especially at higher ATP levels, although other sugars containing two phosphoryl groups may under certain conditions cause activation. PMID- 1591267 TI - Follistatin inhibits activin-induced differentiation of rat follicular granulosa cells in vitro. AB - The effect of follistatin on activin-induced granulosa cell differentiation was investigated in freshly harvested granulosa cells from diethylstilbestrol (DES) treated rats. Activin induced a remarkable change in granulosa cellular morphology from elongated fibroblast-like to round cells, which follistatin prevented. Follistatin itself had no influence on the cellular morphology. We studied the action of follistatin on activin-induced differentiation of granulosa cells cultured in a chemically defined medium. Addition of activin (30 ng/ml) to the culture increased the FSH binding site approximately 2-fold compared with the control (spontaneous expression) level, whereas follistatin reduced the activin induced expression level to the control level in a concentration-dependent manner. Activin (30 ng/ml) markedly augmented FSH-induced hCG binding and progesterone production by approximately 20-fold, and these effects were suppressed by follistatin in a concentration-dependent manner. Similarly, addition of follistatin to the culture induced a concentration-dependent decrease of activin-enhanced inhibin-producing activity, but had no effect on FSH-induced inhibin production. These results suggest that follistatin/activin-binding protein binds to activin stoichiometrically to suppress the activin-induced differentiation of rat granulosa cell in vitro, but follistatin itself has no direct effect on activin-independent reactions. PMID- 1591268 TI - Ligand-affected shift of Na+/H+ exchange pHi set point in human blood platelets, rapidly revealed by a novel approach. AB - The Na+/H+ exchange time-course of BCECF-loaded human platelets, suspended in isotonic media containing NaCl and sodium propionate and activated by intracellular acidification, was measured spectrofluorimetrically. Sequential alkalinization rates decline exponentially as a function of the changing intracellular pH (pHi) and its linear expression (log rate vs. pHi) extrapolates reproducibly to the pHi set point for the Na+/H+ exchange activation. The set point of control platelets (7.28 +/- 0.01) is shifted rapidly (discernibly less than or equal to 30 s) and markedly to alkaline pHi (7.62 +/- 0.03) by PMA, that activates protein kinase C and is shifted to acidic pHi (7.05 +/- 0.01) by staurosporine, which inhibits protein kinases. The addition of 5-N-(3 aminophenyl)amiloride reveals that the alkalinization measured is predominantly Na+/H+ exchange with only a minute contribution (delta pHi = 0.012 +/- 0.002 in 1 min) of an acid loading component, at pHi greater than 7.2. The results support recent studies concluding that the set point indeed reflects the phosphorylation state of the Na+/H+ exchanger. PMID- 1591269 TI - A possible calcium binding site in animal lectins: a 1H-NMR study of the interaction between lanthanides and a synthetic peptide from a highly conserved domain of Pleurodeles lectin. AB - 1H-NMR techniques have been used to study the metal binding properties of a synthetic peptide of 15 amino acids corresponding to a highly conserved domain of Pleurodeles lectin. The addition of lanthanum chloride or praseodymium chloride in a peptide solution induces some conformational changes as displayed by several concerted variations of peptide resonances. The Ln3+ concentration dependence of the chemical shifts was used to calculate the Ln3+ binding constants. The dissociation constants of 95 microM and 280 microM were found for La3+ and Pr3+, respectively. PMID- 1591270 TI - Changes in phosphatidylethanolamine metabolism in regenerating rat liver as measured by 31P-NMR. AB - 31P-NMR spectra of regenerating rat liver in vivo show increases in resonance intensities in the phosphomonoester (PME) region and decreases in the phosphodiester (PDE) region as early as 12 h post partial hepatectomy, which return to normal by 8 days. The compounds primarily responsible for these changes have been identified in perchloric acid extracts as the phosphomonoester phosphoethanolamine and the phosphodiester glycerophosphoethanolamine (GPE), indicating altered phosphatidylethanolamine metabolism. A corresponding increase in diacylglycerol (DAG) levels during regeneration indicates a possible role for a phosphatidylethanolamine-specific phospholipase C in cellular proliferation. These results suggest that changes in phospholipid metabolites previously associated with neoplastic tissue can also be induced by normal tissue undergoing rapid cellular proliferation. The spectral changes observed in the regenerating rat liver are similar to changes seen in spectra from the livers of human patients in several disease states, indicating that 31P-NMR may allow non invasive study of cell turnover in liver disease. PMID- 1591271 TI - Changes in the uptake of transferrin-free and transferrin-bound iron during reticulocyte maturation in vivo and in vitro. AB - The uptake of non-transferrin-bound iron, Fe(II), transferrin-bound iron, Tf-Fe and transferrin was studied in reticulocytes from anaemic rabbits during maturation and then synchronized regeneration in vivo (following injection of actinomycin D) and while maturing during in vitro incubation. The uptake of Fe(II) and Tf-Fe decreased in parallel with each other and with the reticulocyte count and transferrin uptake during maturation in vivo and in vitro. Only during the early phase of reticulocyte regeneration in vivo was there a significant difference between the rates of Fe(II) and Tf-Fe uptake. These results suggest that a membrane carrier for iron and the transferrin receptor are lost at the same rate during reticulocyte maturation, possibly because they are associated with each other in the cell membrane. During reticulocyte maturation the rate of Fe(II) uptake into heme declined more rapidly than uptake into the total cellular cytosol. The loss of transferrin receptors and the uptake of iron from transferrin during reticulocyte maturation was not associated with a change in the affinity of the receptors for transferrin, in the relative distribution of the receptors between the outer cell membrane and intracellular sites or in the ability of the transferrin molecule to donate two iron atoms to the cell with each intracellular cycle, but the average duration of the cycle increased. PMID- 1591272 TI - Temperature dependence of arginine kinase reaction in the tail muscle of live Sycionia ingentis as measured in vivo by 31P-NMR driven saturation transfer. AB - We have employed the driven 31P-NMR saturation transfer method to measure in vivo the temperature dependence of the forward and reverse unidirectional fluxes of the arginine kinase reaction in the tail muscle of a live shrimp, Sycionia ingentis. Our results indicated that neither the forward nor the reverse rate constants of this reaction were significantly temperature-dependent between 8 and 16 degrees C, in contrast to the kinetic characteristics of isolated arginine kinases. PMID- 1591273 TI - Actions of phorbol esters on levels of cAMP in cholera toxin-treated chief cells from guinea pig stomach. AB - Agents like carbachol and cholecystokinin (CCK), that activate chief cell phosphoinositidase C, thereby increasing cell calcium concentration, increase cAMP levels in cholera toxin-treated, but not control, gastric chief cells. In the present study, we found that phorbol esters, like PMA, that activate protein kinase C, also cause augmentation of chief cell cAMP levels. The maximal effect with PMA (100 nM) was about 50% of the maximal response with CCK (10 nM) or carbachol (100 microM). Because protein kinase C is a calcium-dependent enzyme, we examined the effect of modulating cell calcium levels with the ionophore A23187. The ionophore alone caused a dose-dependent augmentation of cAMP levels. Adding 100 nM PMA caused an additive response, such that a maximal cAMP response, equal to that seen with 100 microM carbachol, was observed with 30 nM A23187. Carbachol-, A23187-, and PMA-induced augmentation of cAMP levels was progressively reduced by increasing concentrations of calmidazolium, a calmodulin inhibitor. Combination of phorbol esters that activate protein kinase C with ionophores that increase cell calcium mimics the actions of CCK and carbachol on cAMP levels in cholera toxin-treated chief cells. PMID- 1591274 TI - Involvement of calmodulin- and protein kinase C-related mechanism in an induction process of peroxisomal fatty acid oxidation-related enzymes by hypolipidemic peroxisome proliferators. AB - Trifluoperazine, a calmodulin antagonist, suppressed the clofibric acid-evoked induction of the peroxisomal cyanide-insensitive fatty acyl-CoA oxidizing system and carnitine acetyltransferase in rat liver and also in cultured rat hepatocytes. H-7, a potent inhibitor of protein kinase C, also suppressed the induction of these enzymes by clofibric acid, bezafibrate, Wyl4,643 or mono(2 ethylhexyl)phthalate in cultured rat hepatocytes. This suppressive effect was also confirmed by the protein composition of hepatocytes treated with clofibric acid and these antagonists, where the increase in the amount of peroxisomal bifunctional enzyme by peroxisome proliferator was markedly suppressed by above two antagonists. Profile of the time-dependent changes in the activities of the two enzymes after clofibric acid treatment showed that there might be two phases in the induction process. The initial phase (0-3 days after the treatment) showed a relative low inducing rate and subsequent phase (3-5 days after the treatment) showed an abrupt induction. The suppressive effect of the above two antagonists was significant in the later phase. In a time course study of the induction process of peroxisomal catalase, bifunctional enzyme or 69 kDa integral membrane protein using immunochemical detection, the induction of the membrane protein by clofibric acid was delayed compared with that of the bifunctional enzyme, where the induction was inhibited almost completely by nicardipine. These experimental results suggest that calmodulin- and protein kinase C-dependent processes play an important role in the process of marked induction of peroxisomal enzymes and membrane protein by drugs in rat liver. PMID- 1591275 TI - Glucocorticoid regulation of phospholipid turnover and protein kinase C activity in mouse hepatoma 22 cells. AB - Glucocorticoids induce growth inhibition in certain sensitive hepatoma cells. To investigate how glucocorticoids interact with growth-factor-dependent pathways, we studied the effects of dexamethasone (Dex) on the DNA synthesis, protein kinase C (PKC) activity and phospholipid turnover in mouse hepatoma 22 cells. Dex was found to reduce DNA synthesis in slowly growing hepatoma cells, whereas exponentially growing cells were Dex-insensitive. Direct measurements of PKC activity in the hormone-sensitive hepatoma 22 cells showed a rapid inhibition (within 30 min) when treated with Dex. Dex addition to hormone-sensitive but not to hormone-insensitive hepatoma 22 cells for 30 min caused a significant decrease of 32P-incorporation into the major cellular phospholipids: phosphatidylcholine, phosphatidylglycerol and phosphoinositides. At the same time, the analysis of the correlation between changes in PKC activity and phospholipid turnover showed that synthesis of phosphatidylcholine and phosphatidylglycerol was under positive control of PKC activity. The data suggest that suppression of phospholipid turnover in hormone-sensitive hepatoma 22 cells is one of the early events caused by glucocorticoids, whereas the decrease of PKC activity induced by the hormone is mediated, probably, via changes in phospholipid metabolism. PMID- 1591276 TI - Bradykinin stimulates the production of prostaglandin E2 and interleukin-6 in human osteoblast-like cells. AB - The effect of bradykinin (BK) on proteinase activity, prostaglandin synthesis, and the production of interleukin-6 (IL-6) was investigated in cultures of human osteoblast-like cells. Bradykinin had no effect on stromelysin activity and plasminogen activator activity produced by human osteoblast-like cells. However, BK stimulated the production of prostaglandin E2, an effect that was markedly enhanced by pre-incubation with recombinant interleukin-1 alpha (rhIL-1 alpha), but was apparently unaffected by BK receptor antagonists types 1 and 2. Bradykinin stimulated the intracellular accumulation of total inositol phosphates suggesting that its effects were mediated by stimulation of phosphoinositide metabolism. Bradykinin within the dose range of 10(-11)-10(-5) M also significantly stimulated the production of IL-6. Bradykinin may, therefore, mediate a variety of responses in bone under both physiological and pathological conditions. PMID- 1591277 TI - Identification of AJ-2615 and its S-oxidized metabolites in rat plasma by use of tandem-mass spectrometry. AB - The structural elucidation of the metabolites of a new calcium entry blocker, AJ 2615 (AJ), in rat plasma is described. Metabolites in a crude plasma extract from spontaneously hypertensive rats were identified without chromatographic separation by fast atom bombardment tandem mass spectrometry. When the plasma extract was examined by using parent ion scans, the presence of the oxidized metabolites of AJ was suggested. These metabolites were identified as the S-oxide and the S,S-dioxide by comparing their daughter ion spectra with those of authentic samples. The presence of the two diastereomeric S-oxides of AJ in the plasma extract was ascertained by high-performance liquid chromatography. Their relative configurations were determined by infrared and proton nuclear magnetic resonance spectra. PMID- 1591278 TI - Factors affecting the fast atom bombardment mass spectrometric analysis of proteolytic digests of proteins. AB - The fast atom bombardment (FAB) mass spectrometric analysis of proteolytic digests of proteins is currently used in protein structural characterization. The major current limitation of this procedure is that not all the peptides generated by enzyme digestion can be observed in the spectra. Previous studies showed that in a mixture the more hydrophilic peptides are suppressed. Several enzymatic digests of 18 different proteins ranging from 10 kDa to 67 kDa in molecular weight were examined using FAB mass spectrometry. It was observed that, even though the hydrophobicity of peptides is a factor in determining their presence or absence in the spectra, the predictions of whether or not a peptide would be detected based on this criterion varies in a wide range of values. Moreover, present results seem to indicate that the presence of particular amino acid side chains within a peptide sequence capable of forming hydrogen bonds with the matrix heavily affects the behaviour of that peptide in the mixture, despite the overall hydrophobicity of the peptide itself. PMID- 1591279 TI - Gas chromatographic/mass spectrometric identification of 3-hydroxydicarboxylic acids in urine. AB - Organic acid profiles were routinely analysed for two patients suffering from a massive 3-hydroxydicarboxyluria and five patients suffering from ketoaciduria. The identification of the urinary, saturated and unsaturated 3 hydroxydicarboxylic acids as their trimethylsilyl derivatives was performed with electron impact and positive chemical ionization gas chromatography/mass spectrometry. Additionally, their methylene units have been determined on SE-52 and OV-1701 types of stationary phases. PMID- 1591280 TI - Metabolism of boldenone in man: gas chromatographic/mass spectrometric identification of urinary excreted metabolites and determination of excretion rates. AB - Urinary metabolites of boldenone (androsta-1,4-dien-17 beta-ol-3-one) following oral administration of boldenone (doses from 11 to 80 mg) to man were isolated from urine via XAD-2 adsorption and enzymatic hydrolysis with beta-glucuronidase from Escherichia coli. The isolated metabolites were derivatized with N-methyl-N trimethylsilyltri- fluoroacetamide/trimethyliodosilane and analysed by gas chromatography/mass spectrometry with electron impact (EI) ionization at 70 eV. Boldenone (I) and four metabolites were identified after hydrolysis of the urine with beta-glucuronidase: 5 beta-androst-1-en-17 beta-ol-3-one (II), 5 beta androst-1-ene-3 alpha, 17 beta-diol (III), 5 beta-androst-1-en-3 alpha-ol-17-one (IV) and 5 beta-androst-1-en-6 beta-ol-3,17-dione (V). Five further metabolites in low concentration were identified without enzymatic hydrolysis after treatment of the urine with potassium carbonate: 5 beta-androst-1-ene-3,17-dione (VI), 5 alpha-androst-1-ene-3,17-dione (VII), androsta-1,4-diene-3,17-dione (VIII), androsta-1,4-diene-6 beta,17 beta-diol-3-one (IX) and androsta-1,4-dien-6 beta-ol 3,17-dione (X). The identification of the metabolites is based on the gas chromatography retention index, high-performance liquid chromatography retention, EI mass spectrum, chemical reactions of the isolated metabolites, and synthesis of metabolites II, III, IV, VI and VII. The EI mass spectra of the bis trimethylsilyl derivatives of boldenone and its metabolites display all intense molecular ions, M-15 ions and fragment ions originating from cleavage of the B ring. The excreted metabolites can be separated in basic extractable labile conjugates and in stable conjugates. More than 95% of metabolites are excreted as stable conjugates. PMID- 1591281 TI - Sequencing of cyclodepsipeptides (destruxins) using positive fast atom bombardment desorption tandem mass spectrometry. AB - The development of fast atom bombardment tandem mass spectrometry methodology is applied to the sequencing of the destruxin toxins (cyclodepsipeptides) which are 'wrong' cyclopeptides. The strategy is discussed in detail. Possible ways to overcome problems related to the resolution of isobaric fragment ions using deuterated compounds and the distinction between sequence and retrosequence are examined. PMID- 1591282 TI - Advances in diagnostic techniques of pituitary tumors and prolactinomas. AB - The main advances in the diagnostic evaluation of pituitary tumors and prolactinomas have been in the areas of improved magnetic resonance techniques and in the use of inferior petrosal sinus sampling. New dynamic techniques of rapid acquisition magnetic resonance imaging during bolus contrast infusion have improved the sensitivity for the diagnosis of the small microadenoma. The development of three-dimensional volume imaging has also led to a further improvement in sensitivity to small lesions of the sella. The measurement of adrenocorticotropin levels in the inferior petrosal sinus in patients with Cushing's syndrome assists in the differentiation of adrenocorticotropin secreting pituitary tumor from other peripheral causes of the syndrome. The use of corticotropin-releasing hormone concomitant with sampling has proven to be of value in improving sensitivity and specificity. Elevated levels of growth hormone in petrosal sinus sampling have also been shown to be valuable in the early diagnosis of acromegaly when peripheral hormone levels and imaging are nondiagnostic. PMID- 1591283 TI - Clinical and biologic features in the prognosis and treatment of neuroblastoma. AB - Recent advances in the management of neuroblastoma have their basis in an increasing understanding of the biologic diversity that typifies these tumors. Current therapy is defined by risk of disease progression or relapse and has become best delineated in lower-stage disease and in infants. Older children with disseminated disease continue to exhibit very poor overall outlook, despite recent advances in dose-intensive chemotherapy. This review updates the clinical and biologic features of neuroblastoma that have a significant impact on prognosis and therapeutic design and discusses recent trends and controversies in the treatment of specific subsets of patients. PMID- 1591284 TI - Genetics and cancer. AB - In the past year we have witnessed significant progress in understanding the molecular basis of cancerogenesis and in identifying the genetic determinants of susceptibility to cancer. In particular, the finding that the same tumor suppressor genes play a pathogenic role in both the inherited and the sporadic forms of some childhood tumors has suggested that this gene class may also be involved in adult tumors derived from inherited familial cancer syndromes. The identification of the gene defect underlying the Li-Fraumeni syndrome, a germline mutation of the tumor suppressor gene p53, has fully confirmed that suggestion. Three other genes associated with the inherited cancer syndromes neurofibromatosis type I (NF-1) and familial adenomatous polyposis have been cloned and partially characterized. In addition to these genes, which have a relatively high penetrance and contribute directly to tumorigenesis, other genes that lead to cancer as a secondary effect seem to act in determining an individual's overall cancer risk. The latter genes are most likely related to defective processes of DNA repair or to regulation of carcinogen metabolism. In this context the analysis of models of murine strains with different genetic susceptibility to cancer of various organs may be a useful tool for unveiling the genetic basis for cancer susceptibility in individuals. PMID- 1591285 TI - Pathology and immunology of leukemia. AB - In recent years new developments in cytogenetics, immunophenotyping, and molecular biology have dramatically advanced our understanding of leukemia. Unfortunately, traditional morphologic evaluation of acute myeloblastic leukemia using the French-American-British classification correlates poorly with most of this new information and does not predict response to therapy. In this review we concentrate on applications of molecular biologic techniques to the diagnosis of leukemias, and discuss use of this technology to detect minimal residual disease. We then present a revised classification for acute myeloblastic leukemia according to whether myelodysplasia-like features are present or lacking. Cases may then be further classified using French-American-British morphology and other parameters. This classification appears to correlate better with new biologic data and with therapeutic response. PMID- 1591286 TI - Cell adhesion molecules and cancer. AB - Cell adhesion molecules are complex protein and carbohydrate molecules of many different types found on the surfaces of all cells. They are important in many aspects of cell biology including development, differentiation, and motility. These processes are frequently disturbed in cancer and recent work has demonstrated that disturbances in cell adhesion molecule expression are also common in malignancy. PMID- 1591287 TI - Immunology in cancer. AB - Genetic derangements clearly play an important role in the neoplastic transformation of many, if not all, forms of human cancer. It has become equally apparent, however, that the host response to malignancy often determines the natural history of such transformed cells. Our understanding of the interaction between malignant cells and cellular effectors of the immune system, cytokines, and growth factors has greatly expanded over the past decade, providing the basis for developing specific, effective treatment. Markers for T-cell specificity, including molecular control of cytokine synthesis and T-cell receptor V alpha and V beta usage, have been developed. Transfection of cytokine genes into tumor cells and lymphocytes has provided valuable basic knowledge and a potentially important new form of treatment. This review discusses these and other important new developments in immunology and cancer research, emphasizing the complexity of the immune system and its response to cancer. PMID- 1591288 TI - Leukemia. PMID- 1591289 TI - Endocrine tumors. PMID- 1591290 TI - Cancer biology. PMID- 1591291 TI - Cytogenetics and oncogenes in leukemia. AB - Cytogenetic and molecular studies have assumed an increasing role in the evaluation and management of patients with leukemia. Many cytogenetic findings have become well established as important independent indicators of prognosis in the acute leukemias. There has been a recent explosion of knowledge about the genes involved in leukemogenesis and the manner in which their structure or expression is altered by chromosomal translocations or point mutations. Application of newer techniques such as the polymerase chain reaction and in situ hybridization has begun to allow quantitation of residual leukemia cells after therapy. Cytogenetic and molecular findings should allow us to use more individualized therapy in treating leukemia, as well as therapy targeting leukemia-specific abnormal gene products. PMID- 1591292 TI - Unknown primary tumors. PMID- 1591293 TI - Hematopoietic growth factors and leukemia. AB - Hematopoietic growth factors, particularly granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, can be used as supportive agents to enhance bone marrow recovery after the administration of myelosuppressive chemotherapy given for nonmyeloid neoplasms. The use of these agents in the treatment of acute myeloid leukemia and myelodysplastic syndrome poses novel opportunities and challenges due to their direct effects on the neoplastic cells, which represent the transformed counterparts of normal hematopoietic stem cells. The interaction between hematopoietic growth factors and leukemic progenitor cells bearing a specific receptor for a given agent would be expected to result in proliferation, although maturation induction could occur. Hematopoietic growth factors have been employed as primary differentiating agents in myelodysplastic syndrome and as supportive agents after chemotherapy in acute myeloid leukemia. In either case, close monitoring for evidence of leukemic stimulation is required. Alternatively, pretreatment with colony-stimulating factors could induce cell cycling, thereby making the leukemic cells more susceptible to S-phase-specific chemotherapeutic agents, such as cytarabine. PMID- 1591294 TI - Treatment of acute leukemia in adults. AB - The goal of therapy for young adults with de novo acute myeloid leukemia is cure. Seventy percent or more of young adults achieve initial remission, and 30% to 40% of adults receiving postremission chemotherapy appear to remain in remission. High-dose cytarabine consolidation therapy appears particularly effective. However, with current approaches, only 20% of young adults are cured. New approaches are needed to increase the cure rate substantially, and autologous bone marrow transplantation appears to be the most promising treatment modality in acute myeloid leukemia. Improved preparative regimens and purging techniques may be critical factors in determining the effectiveness of autologous bone marrow transplantation. In adult acute lymphoblastic leukemia, very high remission rates are now being reported with intensive multiagent induction therapy, and approximately one third of young adults with this disease are cured with current intensive chemotherapy approaches. The role and optimal methods of bone marrow transplantation for acute lymphoblastic leukemia are under investigation. PMID- 1591295 TI - Chronic myeloid leukemia. AB - Chronic myeloid leukemia is an enigma in origin and a source of frustration in treatment because until recently no real progress had been made in altering its natural history. Nevertheless, recent advances in cell biology and molecular genetics, and a plethora of morphologic, biochemical, and cytogenetic data of potential clinical relevance have yielded new data regarding this disease. The use of marrow transplantation and recombinant interferon have been of significant clinical importance, although their roles in the overall treatment of the disease remain to be determined. PMID- 1591296 TI - Biology and treatment of multiple myeloma. AB - Multiple myeloma remains a fatal disease. However, in the last few months new biologic and clinical information has been provided about this disease. In particular, the immunophenotype of myeloma cells seems to indicate, at least in some patients, the possibility of a stem cell involvement in the pathogenesis of myeloma. Moreover, the recent progress in understanding the complex cytokine network has revealed the possibility that myelomatous proliferation is highly influenced by some cytokines such as interleukin-6, interleukin-3, interleukin-2, and granulocyte-macrophage colony-stimulating factor. Furthermore, it has been shown that the mechanism responsible for the resistance of myeloma cells to chemotherapy may be partially overcome by the use of calcium antagonists associated with quinine. Finally, new insights into the pathogenesis and biology of the disease have been provided by studies of molecular biology and flow cytometry undertaken in multiple myeloma patients. The best conventional induction treatment remains to be defined. However, the increased use, as new therapeutic modalities, of interferon-alpha and transplantation procedures in multiple myeloma opens new hopes of a cure. In the future, a better comprehension of the multiple myeloma biology associated with a wider use of new and more effective therapeutic approaches will certainly improve the natural course of the disease. PMID- 1591297 TI - Diagnosis and treatment of thyroid, adrenal, and thymic tumors. AB - The authors review 41 recent articles concerning the diagnosis and treatment of thyroid, adrenal, and thymic tumors. Diagnostic and evaluative techniques for thyroid nodules are inexact; fine-needle aspiration cytology offers the best results. Most authors favor total thyroidectomy and postoperative 131I ablation. The issue of elective versus therapeutic cervical lymphoidectomy remains controversial. Chemotherapy is of very little use in treating differentiated thyroid carcinoma. The most useful follow-up technique is whole-body scanning in conjunction with thyroglobulin determination. Persistent hypercalcitoninemia after surgery for medullary thyroid carcinoma is not uncommon and does not necessarily indicate demonstrably recurrent disease. In imaging adrenal tumors, magnetic resonance imaging appears to have some advantages over computed tomography. Pheochromocytomas may not always present classically; a clear understanding of the biochemical diagnosis is essential. Patients with thymomas have a good prognosis. Surgical treatment of encapsulated thymomas is appropriate, although more extensive thymomas are best treated multimodally. PMID- 1591298 TI - Animal experimentation relevant to human marrow transplantation. AB - Animal experimentation has advanced the understanding of cellular events in the afferent and efferent phases of graft-versus-host disease. New immunosuppressive agents such as FK-506, deoxyspergualin, and interleukin-1 receptor antagonist have shown successful prevention and treatment of graft-versus-host disease in rats and mice. Pretransplant and posttransplant immunosuppressive regimens capable of enhancing engraftment of T-cell-depleted marrow have been defined in murine marrow transplantation. Evidence has begun to emerge indicating that engraftment can be enhanced by T cells that do not cause graft-versus-host disease. Finally, investigations have begun to define approaches for enhancing graft-versus-leukemia effects not only in allogeneic marrow transplantation but also in autologous transplantation. PMID- 1591299 TI - Modern trends in bone marrow transplantation for acute myeloid and acute lymphoblastic leukemia. AB - A greater understanding of the underlying mechanisms of hematopoiesis and leukemogenesis in the clinical management of acute myeloid and lymphoblastic leukemia has led to an improvement in survival from what were invariably fatal diseases. Bone marrow transplantation is increasingly becoming an accepted form of therapy for acute myeloid leukemia and acute lymphoblastic leukemia in certain situations. This review seeks to address some of the recent advances and controversies including whether bone marrow transplantation is more efficacious than modern intensive chemotherapy, the role of autologous bone marrow transplantation and matched-unrelated donor transplants, the graft-versus leukemia effect, and the role of purging in autologous bone marrow transplantation. Furthermore, advances in supportive therapy including the introduction of hematopoietic growth factors is critically evaluated. Finally, the appropriate timing and role of bone marrow transplantation is discussed in the context of previous ongoing and future clinical trials. PMID- 1591300 TI - Bone marrow transplantation for chronic myelogenous leukemia. AB - It is generally accepted that patients with chronic myelogenous leukemia in chronic phase under the age of 50 years who have HLA-identical siblings, should be offered bone marrow transplantation within the first year of diagnosis. The projected disease-free survival for these patients is 70% to 80% at 4 years, and most of these will prove to have been cured. Results of bone marrow transplantation for patients with more advanced disease are less promising. For transplant conditioning there is no important difference between cyclophosphamide plus total-body irradiation and busulphan plus cyclophosphamide. Nonenlarged spleens require neither splenectomy nor additional radiotherapy. The use of cyclosporine and methotrexate is currently the optimal approach to graft-versus host disease prevention. Fewer good results are obtained with "matched" volunteer marrow donors. Use of the polymerase chain reaction to monitor residual BCR-ABL transcripts after bone marrow transplantation may prove useful in identifying patients at increased risk for relapse. Autografting may offer the prospect of prolonged life or even cure for patients without suitable allogeneic donors. PMID- 1591301 TI - Purging in autologous and allogeneic bone marrow transplantation. AB - The success of hematoablative dosages of cytotoxic therapy followed by stem cell transplantation depends on the disease response to the intensive drug dose and the ability of the transplant to provide durable hematopoietic reconstitution. In autologous stem cell transplantation, patients' own bone marrow or peripheral blood is used for hematopoietic engraftment. In several diseases the bone marrow is involved, and in such situations, the success of autologous stem cell transplantation may improve if the hematopoietic elements are enriched (positive selection) or if the contaminating cancer cells are purged by negative selection. In patients undergoing allogeneic bone marrow transplantation, the T lymphocytes of the donor cells contribute to the development of graft-versus-host disease with significant morbidity and mortality. Selective purging of T lymphocytes has dramatically decreased the incidence of graft-versus-host disease. In this paper, various methods for purging hematopoietic stem cells are detailed with emphasis on treatment planning. Exciting new possibilities include growing stem cells from a small amount of bone marrow, enhancing immune surveillance, and decreasing drug resistance by genetic engineering. PMID- 1591302 TI - Autologous bone marrow transplantation for breast cancer. AB - There will be an estimated 180,000 new cases of breast cancer this year with 46,000 deaths. Adjuvant chemotherapy is now firmly established as a valuable modality in breast cancer, improving both disease-free and overall survival in appropriate patients. Unfortunately, chemotherapy has yielded little improvement in the survival of patients with metastatic breast cancer. PMID- 1591303 TI - Epidemiology, prevention, prognostic factors, and natural history of lung cancer. AB - In the year under review, studies showed the effects of smoking on the occurrence of lung cancer outside North America; currently, China is a country of considerable interest. A number of studies were also reported on occupational factors in lung cancer etiology, with risks confirmed in the steel industry. Increasing interest, mostly generated by the tobacco industry, relates to passive smoking and lung cancer. Attempts continue to refine prognostic factors, especially in small cell lung cancer. PMID- 1591304 TI - The biology of lung cancer. AB - The incidence of lung cancer continues to rise worldwide with major increases in incidence observed in Third World countries. Unfortunately, the overall survival of patients with this disease has remained unchanged in the past 2 decades. In spite of this, there have been major advances in understanding the biologic properties of both small cell and non-small cell lung cancer, including the definition of specific autocrine growth factors, molecular advances associated with the pathogenesis of this disease, and determinants of the mechanism of drug resistance. Here we review the most recently recognized important biologic properties of lung cancer cells in vitro and in vivo and discuss the clinical relevance of application of these biologic properties in the management of patients with this disease. PMID- 1591305 TI - Paraneoplastic syndromes in lung cancer. AB - Paraneoplastic syndromes are caused by factors produced by cancer cells that often act at a site distant from both the primary site and its metastases. These syndromes are estimated to occur in only 7% to 15% of patients with cancer and are diagnoses of exclusion. If the definition of paraneoplastic syndrome is broadened to include indirect effects of the tumor such as cachexia or the anemia of chronic disease, the incidence is much higher. Lung cancer, particularly small cell lung cancer, is the most common malignancy causing paraneoplastic syndromes. This review focuses on recently published literature on paraneoplastic syndromes associated with lung cancer, including humoral hypercalcemia of malignancy, autoimmune paraneoplastic neurologic syndromes, neuromuscular disorders, and cancer cachexia. It includes advances in both molecular biology and immunology, and in clinical investigation. PMID- 1591306 TI - Pleural mesothelioma. AB - Diffuse pleural malignant mesothelioma (DMM) is an uncommon tumor in the general population, but its incidence can be very high in persons exposed to asbestos. There has been controversy about the role of the different fiber types and their responsibility for causing DMM, particularly with chrysotile. Distinguishing between DMM and peripheral adenocarcinoma with pleural involvement is a frequent diagnostic problem. Immunohistochemical markers (positive for vimentin and negative for carcinoembryonic antigen and Leu M1) and electronmicroscopy aid in the diagnosis. Therapeutic results remain poor, and cure of DMM is rare. Local treatments such as surgery or radiation therapy are technically difficult because of the extent of disease. DMM continues to be a chemoresistant tumor. Because DMM is rare, study of this tumor has been hampered by the limited number of available patients in any given institution. Therefore, animal models or representative human malignant mesothelioma cell lines are needed for a dual investigation: first of the basic biology of this disease and second for a preclinical evaluation of chemotherapeutic agents and recombinant anticancer cytokines alone or in combination. Ongoing trials confirm that DMM is resistant to standard forms of therapy, but mesothelial cells are susceptible to immune effector cells and cytokines in in vitro and in vivo models. Thus, recombinant interferon-alpha, beta, and -gamma have been used for both local and systemic treatment, as has interleukin-2 with and without autologous lymphokine-activated killer cells. In addition, substantial experimental evidence suggests synergy between cytotoxic drugs and cytokines. PMID- 1591307 TI - Etiology, risk factors, epidemiology, and public health issues in melanoma and other cutaneous neoplasms. AB - The cytogenetic features of melanoma, including the contribution of specific genes, are beginning to be unraveled. Reproductive factors have been shown to have little relationship to melanoma. The puzzles over apparent systemic effects of exposure have persisted, however. Evidence was published that the history of reaction to sun exposure altered when a diagnosis of melanoma was made. An interesting suggestion was made that the classic melanoma risk factors are associated with promotion rather than initiation of the disease. There is further evidence that exposure decreases melanoma risk in people who tan well but increases it in those who do not. Also reviewed is the evidence that the ozone layer of the stratosphere began to decrease in thickness under the influence of the chlorofluorocarbon gasses. PMID- 1591308 TI - Tumor progression, biology, and host response in melanoma. AB - Malignant melanoma has provided an excellent model system for studying crucial events in human tumor development and progression. Important components discussed here include the independence of melanoma cells from exogenous growth factors due to self-stimulation and the altered adhesive properties and invasive capacity of these cells. PMID- 1591309 TI - Clinical and pathologic diagnosis, staging and prognostic factors of melanoma and management of primary disease. AB - To increase detection of melanoma, medical practitioners and the general public should know the signs of early invasive melanoma. The Scottish Melanoma Group recently presented a revised checklist of the major and minor signs. The validity of the reported clinical and histopathologic criteria for the dysplastic nevus, a precursor to cutaneous melanoma, is not fully established. However, expert pathologists agreed on the use of major and minor criteria. The differential diagnosis between spindle-epitheloid cell nevi and melanoma remains problematic, because the former lesions often show cellular atypia. Other lesions that can cause considerable diagnostic difficulties are melanoma in situ and minimal deviation melanoma. Immunohistochemical studies of human melanocytic lesions have contributed to the diagnosis of poorly differentiated tumors but, so far, have not helped in the discrimination among benign, premalignant, and malignant lesions. They have provided additional prognostic information in cases of primary melanoma and locoregional melanoma metastasis. Quality control of antibody reagents continues to be a problem. Microstaging of primary melanoma using Breslow depth and Clark's level of invasion may be subject to considerable intra- and interobserver variation. To improve the accuracy of the measurements, using a vernier scale is recommended. The type of melanoma is relevant in considering clinicopathologic prognostic factors. Acral melanoma (for example, that arise from glabrous skin) has been reported to carry a grave prognosis. Polypoid melanoma may have a less unfavorable outlook than previously thought. DNA cytophotometry provides prognostic information in case of primary melanoma but loses significance when stratified for tumor thickness. In patients with lymph node-positive melanoma, however, DNA ploidy analysis appears to yield additional prognostic information. In the management of primary disease, the width of the surgical excision and whether to approach the regional lymph nodes remain the main issues. A multicenter study conducted by the World Health Organization Melanoma Programme has found that a "narrow" excision is a safe procedure for primary melanomas not thicker than 1 mm. Several investigators underline the need for continued annual follow-up for all melanoma patients; recurrence may occur late. Currently, elective lymph node dissection is not recommended in the management of "thick" primary melanoma. Because data from randomized trials conducted in patients with a tumor of intermediate thickness are not yet available, only guidelines on management offered by experienced surgeons can be given. Patients with the dysplastic nevus syndrome should be closely followed so that melanomas can be diagnosed as early as possible. PMID- 1591310 TI - Preclinical studies, experimental therapeutics, and clinical management of advanced melanoma. AB - The preclinical and clinical investigations of therapeutic approaches to melanoma have progressed significantly in the past year. This article reviews recently published information relevant to preclinical studies of the biologic function of stromal tissue, growth factors (and receptors), interferons, cytokines, and antimetabolites as well as clinical studies of agents that may alter host-tumor interactions. Data published over the past year include new advances in the use of cytokines with and without adoptive cellular transfer, as well as tumor cell antigens for immunization and monoclonal antibodies for passive transfer. The data suggest that the age-old dogma that no medical treatment of melanoma prolongs survival may soon be a thing of the past. PMID- 1591311 TI - Basal cell and squamous cell carcinoma and Kaposi's sarcoma. AB - The mortality rate of nonmelanoma skin cancer is higher than generally considered. An actual nonmelanoma skin cancer is a risk factor not only for other skin cancers but also for cancers in other organs. The recurrence rate can, according to the method of calculation, yield surprisingly diverging results. Statistical mapping of subclinical tumor growth in basal cell carcinoma supplies the margins for tumor-free excision. An even better but more expensive tool for therapy planning is tumor imaging with magnetic resonance imaging. Psoralen plus ultraviolet light of the A wavelength-treated patients run a dose-dependent risk of developing squamous cell carcinoma of the skin but also cancers in other organs. Human papilloma virus-16 seems not to be associated with squamous cell carcinoma of the skin except for the anogenital region and possibly the finger. The finding of retroviruslike particles in endemic non-acquired immunodeficiency syndrome Kaposi's sarcoma strongly suggests that a virus other than human immunodeficiency virus may play a role in the pathogenesis of this disease. PMID- 1591312 TI - Transplantation. PMID- 1591313 TI - Lung and mediastinum. PMID- 1591314 TI - Melanoma and other skin neoplasms. PMID- 1591315 TI - Vitamin C and reduced mortality. PMID- 1591316 TI - What causes Kaposi's sarcoma? Inquiring epidemiologists want to know. PMID- 1591317 TI - Vitamin C intake and mortality among a sample of the United States population. AB - We examined the relation between vitamin C intake and mortality in the First National Health and Nutrition Examination Survey (NHANES I) Epidemiologic Follow up Study cohort. This cohort is based on a representative sample of 11,348 noninstitutionalized U.S. adults age 25-74 years who were nutritionally examined during 1971-1974 and followed up for mortality (1,809 deaths) through 1984, a median of 10 years. An index of vitamin C intake has been formed from detailed dietary measurements and use of vitamin supplements. The relation of the standardized mortality ratio (SMR) for all causes of death to increasing vitamin C intake is strongly inverse for males and weakly inverse for females. Among those with the highest vitamin C intake, males have an SMR (95% confidence interval) of 0.65 (0.52-0.80) for all causes, 0.78 (0.50-1.17) for all cancers, and 0.58 (0.41-0.78) for all cardiovascular diseases; females have an SMR of 0.90 (0.74-1.09) for all causes, 0.86 (0.55-1.27) for all cancers, and 0.75 (0.55 0.99) for all cardiovascular diseases. Comparisons are made relative to all U.S. whites, for whom the SMR is defined to be 1.00. There is no clear relation for individual cancer sites, except possibly an inverse relation for esophagus and stomach cancer among males. The relation with all causes of death among males remains after adjustment for age, sex, and 10 potentially confounding variables (including cigarette smoking, education, race, and disease history). PMID- 1591318 TI - Evidence for a sexually transmitted cofactor for AIDS-related Kaposi's sarcoma in a cohort of homosexual men. AB - We examined factors associated with the subsequent development of AIDS-related Kaposi's sarcoma in a cohort of 353 homosexual men infected with human immunodeficiency virus (HIV). Cumulative incidence curves for the development of Kaposi's sarcoma and opportunistic infection were stratified over a wide range of variables at enrollment, including those related to demographics, sexual behavior, illicit drug use, and medical history. We found no strong associations between any of these variables and the development of opportunistic infection, but two were related to Kaposi's sarcoma: use of nitrite inhalants (relative risk, 2.3; 95% confidence interval, 1.0-5.0) and high numbers of sexual contacts during the period 1978-1982 in the AIDS epidemic centers of San Francisco, Los Angeles, and/or New York (relative risk, 3.5; 95% confidence interval, 1.6-7.6). The latter variables remained independently associated with risk of Kaposi's sarcoma even after multivariate adjustment for a number of classical HIV risk factors. These results are consistent with the hypothesis that Kaposi's sarcoma is caused by a sexually transmitted cofactor that has remained more prevalent in the original epidemic centers. The effect of nitrites could be due to an independent biological mechanism or to enhancement of transmission of the cofactor. PMID- 1591319 TI - Bias from nondifferential but dependent misclassification of exposure and outcome. AB - When misclassification of exposure and disease is nondifferential but not independent of one another, bias away from the null can result. For dichotomous variables, misclassification is nonindependent when the probability of misclassification of one variable is dependent on the correctness of classification of the other variable. One plausible form of nonindependent misclassification may result from variation in the threshold for reporting exposure and outcome by study subjects. The odds ratio after dependent misclassification can be expressed as a function of the true odds ratio, the prevalences of exposure and outcome, and the probabilities of misclassification. When prevalences of exposure and outcome are low, bias may be considerable even at low probabilities of misclassification. The nonindependent misclassification described in this article will result in a positive bias in the odds ratio and is therefore of prime concern when questioning the validity of an observed effect. The core of the problem lies in the study design and can be solved by eliminating the common link that makes nonindependent errors possible. PMID- 1591320 TI - Use and limitations of dual measurements in correcting for nondifferential exposure misclassification. AB - Recently, several authors have encouraged the use of dual measurement strategies to correct for bias due to nondifferential misclassification in epidemiologic research. Among these, latent class techniques, which give unbiased results if both measurements are independent conditional on the true value, have become most popular. In practice, however, measurement errors are usually more likely to be positively correlated, and hence reliability studies cannot replace studies of validity. I offer here a quantitative illustration and a comparison of the performance of latent class approaches and other dual response strategies in situations of positive error covariance. I conclude that, except under very special circumstances, dual measurement strategies are likely to remove only part, if any, of the effect attenuation due to nondifferential exposure misclassification. Under certain conditions, it may make sense, however, to estimate a "minimum" effect of the exposure on the basis of the strongest association found in various dual and single measurement strategies. PMID- 1591321 TI - Misclassification of exposure in a case-control study: the effects of different types of exposure and different proxy respondents in a study of pancreatic cancer. AB - This investigation addressed three questions about misclassification in a case control study of risk factors for pancreatic cancer in which all exposure data were obtained from proxy respondents. These questions were: (1) To what degree was misclassification dependent on the type of exposure? (2) To what degree did misclassification vary by the type of proxy? (3) What was the magnitude of the effect of proxy misclassification on odds ratios measured across several levels of exposure? To answer these questions, we interviewed 163 control (index) subjects and next-of-kin (proxy) respondent pairs. Each of the controls and their respective proxies reported the control's use of coffee, cigarettes, and alcohol and weekly exposure to beef, milk, bacon, fruits, and vegetables. Nonspouse proxies misclassified exposures more than spouse proxies with the exception of cigarettes. Cigarette use was the most accurately reported exposure, followed by alcohol, coffee, and foods. For nondifferential misclassification between cases and controls, the slope of a dose-response curve was decreased from 6.6% to 100% depending on the exposure and the type of proxy respondent. Investigators conducting studies using proxy respondents need to recognize that misclassification is a function of multiple factors, including both the type of exposures under study and the type of proxies available. PMID- 1591322 TI - Incidence of insulin-dependent diabetes mellitus in Colorado. AB - We examined the incidence of insulin-dependent diabetes mellitus in children 0-17 years of age in Colorado from 1978 to 1988. Cases were ascertained from a statewide registry based on physician surveillance. A total of 1,376 children were diagnosed during this interval in a population averaging 860,000 children. The degree of ascertainment was estimated to be 93.3%. The age-adjusted incidence rate of insulin-dependent diabetes mellitus was 14.8/100,000 person-years. The rate was lower in individuals of Spanish origin (Hispanics) (8.7/100,000 person years) compared with non-Hispanic individuals (15.5/100,000 person-years) (incidence rate ratio = 0.6, 95% confidence interval = 0.4-0.8). Incidence rates were higher in winter and lower in summer for children 5-17 years old. Children diagnosed before the age of 5 years showed no significant seasonal pattern, although peak incidences were observed in autumn and spring. No temporal trend in diabetes incidence was observed overall or by ethnic group. The increasing insulin-dependent diabetes incidence reported by registries in Europe during this time period was not observed in Colorado. PMID- 1591323 TI - The relation of computer-based measures of sperm morphology and motility to male infertility. AB - We investigated the relation between various sperm characteristics, including morphometric parameters, and impaired fertility among 596 men who participated in a national study. Semen was collected and processed by using a standardized protocol, and sperm measurements were made using a computer-aided sperm analysis instrument. We defined infertility in two ways: (1) the inability to father a child after trying for a year or longer, and (2) the number of children fathered. We found that all measures of sperm motion were decreased among men with impaired fertility. After adjustment for the other motion parameters and various potential confounders, however, only the percentage of progressive cells was associated with infertility. One morphometric parameter, the mean length/width ratio, was consistently associated with both measures of infertility, even after adjustment for potential covariates. This measure was also strongly associated with infertility among various subgroups defined by poor sperm concentration, motility, and morphology. The sperm length/width ratio appears to be an important correlate of infertility in males. PMID- 1591324 TI - Interrelationships of relative risks of birth defects in embryonic and fetal deaths, in livebirths, and in all conceptuses. AB - Most studies of associations with birth defects are undertaken in livebirths. An observed association in livebirths different from unity may be compatible with no association in conceptuses if "balanced" by a particular relative risk in embryonic and fetal deaths. We derived formulae to address the following queries: (1) If one observes in livebirths a relative risk of birth defect, tau def,lb, then, with what combinations of relative risk of defect in embryonic and fetal deaths, tau def,efd, and in all conceptuses, tau def, is this value compatible? (2) What balancing relative risk in embryonic and fetal deaths is predicted if there is no causal association in all conceptuses? (3) Under what circumstances is there no relative risk in embryonic and fetal deaths that can balance an observed relative risk in livebirths? We present an expression for tau def,efd in terms of five other variables: tau def,lb, tau def, and tau efd (the relative risk of embryonic or fetal death), and the lethalities of the average (unexposed) conceptus and of the (unexposed) defective conceptus. This equation enables one to derive the balancing relative risk in embryonic and fetal deaths, bal tau def,efd, which is the value of tau def,efd when tau def = 1.0. If bal tau def,efd is negative, no such balancing relative risk exists, and any observed association in livebirths is incompatible with a null association in all conceptuses, that is, the association cannot be explained completely by differential selection of conceptuses with defect. PMID- 1591326 TI - Mortality among laboratory workers employed at the U.S. Department of Agriculture. AB - We evaluated the mortality of 835 white male and 36 female laboratory workers employed by the U.S. Department of Agriculture who died between January 1, 1970, and December 31, 1979. For males, the mortality odds ratio for all cancers was 1.0 (95% confidence interval = 0.8-1.2). Colon cancer, lymphosarcoma and reticulosarcoma, nonmalignant diseases of the blood and blood-forming organs, and suicide showed elevated mortality odds ratios. Only colon cancer showed an association with duration of employment as a laboratory worker. In an accompanying case-control study, the risk of colon cancer rose to 3.2 among those who had 20 or more years of employment as a laboratory worker. Among females, breast cancer was elevated (mortality odds ratio = 5.3; 95% confidence interval = 2.8-10.1). PMID- 1591325 TI - Forced expiratory volume (1 second) and lung cancer incidence and mortality. AB - We evaluated the relation between forced expiratory volume in 1 second (FEV1) and lung cancer incidence and mortality among members of the Kaiser Permanente Medical Care Program who took a multiphasic health checkup. FEV1 was inversely related to risk of lung cancer among former and current smokers, but not related among never-smokers. We observed a decreased risk of lung cancer mortality only in the higher quintiles of FEV1 in current smokers among men, but not in women. FEV1 appears to be associated with lung cancer as a physiologic marker for smoking-induced pulmonary damage. PMID- 1591328 TI - The bootstrap method for standard errors and confidence intervals of the adjusted attributable risk. PMID- 1591327 TI - Is water pollution a cause of cutaneous melanoma? PMID- 1591329 TI - The bootstrap method for standard errors and confidence intervals of the adjusted attributable risk. PMID- 1591330 TI - Coffee consumption and reproductive failures. PMID- 1591331 TI - Leukemia among nuclear workers with protracted exposure to low-dose ionizing radiation. PMID- 1591332 TI - Isolation, immunolocalization, and sperm-association of three proteins of 18, 25, and 29 kilodaltons secreted by the mouse epididymis. AB - Three murine epididymal secretory proteins have been characterized by their site of synthesis, sperm association, and tissue localization by use of polyclonal antisera and immunochemistry. Mouse epididymal protein 7 (MEP 7) was localized initially within the supranuclear regions of some principal epithelial cells in the proximal corpus while other cells remained unstained. In the mid-proximal corpus, all principal cells and stereocilia were stained, and luminal staining increased from corpus to cauda. Some clear cells in the distal corpus and cauda also showed immunoperoxidase staining. Sequential extraction of caudal spermatozoa indicated that MEP 7 was predominantly loosely associated with spermatozoa and that only a small amount of MEP 7 required detergent to extract it from spermatozoa. Examination of other rodent caudal fluids revealed a related protein in rat caudal fluid of 32 kDa, and amino acid sequence analysis of MEP 7 showed a 68% sequence similarity with rat proteins AEG and D/E. MEP 9 immunolocalized within the cytoplasm of all principal cells of the distal caput. In a transition zone between the distal caput and the corpus, some principal cells were stained while others were not. Distal to the corpus, the principal cell staining gradually decreased. In the distal caput and proximal corpus, large heavily stained droplets associated with spermatozoa were seen in the lumen. The staining intensity of these droplets also decreased from corpus to cauda. The clear cells of the distal corpus and cauda did not stain with the antibody to MEP 9. Sequential extraction of caudal spermatozoa showed that some MEP 9 was extractable under low-salt conditions, whereas extraction with 0.1% Triton X-100 was required to remove all MEP 9, indicating it was firmly associated with spermatozoa. The antibody to MEP 9 cross-reacted with a 25-kDa protein present in rat caudal fluid. MEP 10 was localized within the cytoplasm of the principal cells, the stereocilia, and the lumen of the epididymis at the junction of the distal caput and corpus. In the distal corpus, a large number of clear cells were stained, but very few of these cells stained in the cauda. MEP 10 dissociated completely from caudal spermatozoa under low-salt conditions, indicating that it was not firmly bound to spermatozoa. The antiserum to MEP 10 cross-reacted with proteins present in rat and guinea pig caudal fluid. The related rat protein migrated at approximately 20 kDa. Amino acid sequence analysis of MEP 10 revealed an 86% sequence similarity with rat proteins B and C.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1591334 TI - Hyperactivated sperm progress in the mouse oviduct. AB - Sperm from naturally mated mice were observed and videotaped moving within mouse oviducts. The typical pattern of sperm progress involved intermittently breaking free and swimming a short distance, then reattaching to the epithelium. The proportion of sperm that swam freely (were not attached to the epithelium) was calculated and analyzed for effects of oviductal region, ovulation status, and sperm location relative to the lumen. A significantly higher proportion of sperm were free in the ampulla than in the isthmus (26.3% +/- 0.8% vs. 11.8% +/- 1.0%; p less than 0.0001) and in post-ovulatory than pre-ovulatory (16.2% +/- 2.0% vs. 10.6% +/- 1.6%; p less than 0.05) oviducts. Flagellar curvature ratio values showed that free sperm (0.716 +/- 0.024) had more sharply curved tails than stuck sperm (0.782 +/- 0.013). While this difference is significant (p = 0.01), the effect of attachment status interacted significantly (p less than 0.05) with the oviductal region such that there was a greater difference in the isthmus than in the ampulla. Only sperm using the more curved tail beats of hyperactivation were seen to break free from the epithelium and to progress along the oviduct. These results indicate that hyperactivation plays a role in moving sperm out of the isthmic reservoir and to the site of fertilization. PMID- 1591333 TI - The 18-kDa mouse epididymal protein (MEP 10) binds retinoic acid. AB - Mouse epididymal protein (MEP) 10 has recently been characterized in our laboratory. Amino acid sequence analysis of the N-terminal of MEP 10 revealed an 86% similarity in sequence with rat proteins B and C, characterized by Brooks and Higgins [J Reprod Fertil 1980; 59:363-375]. Proteins B and C, have been recently shown to possess retinoic acid-binding ability [Newcomer ME, Ong DE. J Biol Chem 1990; 265:12876-12879; Ong DE, Chytil F. Arch Biochem Biophys 1988; 267:474-478]. Therefore, it was of interest to determine whether MEP 10 possessed the same ability to bind retinoic acid. Mouse caudal fluid was trace-labeled with 3H retinoic acid and applied to a DEAE ion-exchange column. Analysis of the fractions for both the presence of radioactivity by scintillation counting and MEP 10 by ELISA revealed that the peak of radioactivity corresponded to the peak of MEP 10 immunoreactivity. These peak fractions were pooled and used for subsequent binding analysis and SDS-PAGE and Western blot analysis. SDS-PAGE and Western blot analysis revealed that the peak fractions were enriched for a protein of 18 kDa and that this protein was MEP 10. Competitive binding assays revealed that all-trans-retinoic acid was effective in inhibiting binding of labeled retinoic acid, but that the 13-cis isomer of retinoic acid was only moderately effective in inhibiting binding of the labeled ligand. All-trans retinol was ineffective in the binding inhibition assay. Similar ligand specificity has also been described for the rat proteins B and C by Ong and Chytil [Arch Biochem Biophys' 1988; 267:474-478].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591335 TI - Isolation of human Leydig cell mesenchymal precursors from patients with the androgen insensitivity syndrome: testosterone production and response to human chorionic gonadotropin stimulation in culture. AB - Mature Leydig cells, the main source of testicular testosterone in mammals, arise from immature mesenchymal precursors through an LH-dependent differentiation process. In order to study the steroidogenic potential of these precursors, undifferentiated mesenchymal cells were obtained from the testicular interstitium of two patients with androgen insensitivity syndrome. After double digestion with collagenase and separation of the suspensions in a Percoll density gradient, the cells were cultured in Ham's F12 medium: Dulbecco's Modified Eagle Medium (1:1) supplemented with antibiotics, transferrin, insulin, hydrocortisone, and vitamin E with or without 1 IU of hCG/ml. At 11 days in culture, samples were removed for morphological characterization and determination of 3 beta-hydroxysteroid dehydrogenase activity (3 beta-HSD). Testosterone concentration was determined by RIA in the culture medium at different intervals. Cultured cells were mesenchymal in appearance, elongated in shape, with numerous processes running in different directions. No mature Leydig cells were present. In basal conditions, the percentages of 3 beta-HSD-positive cells at 11 days on patients 1 and 2 were 33% and 28%, respectively, and the testosterone concentrations in the culture media were 4.8 and 8.4 ng.10(6) cells.24 h, respectively. In cultures stimulated with hCG, there was an increase of histochemical reactivity (47% and 42% in patients 1 and 2, respectively) and in the amount of testosterone secreted (10.2 and 12.0 ng.10(6) cells, respectively). Electron microscopic studies of cultures grown in the absence of hCG demonstrated a homogenous population of poorly differentiated, fibroblastic-type mesenchymal cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591336 TI - Developmental changes in endogenous retinoids during pregnancy and embryogenesis in the mouse. AB - Vitamin A and its analogs (retinoids) have acquired particular significance in embryonic development since the discovery that retinoic acid (RA) possesses properties of an endogenous morphogen and that embryonic tissues contain specific nuclear receptors for RA. Since the mammalian embryo does not synthesize RA de novo but rather must acquire it directly or in a precursor form from the maternal circulation, we sought to establish the relationship between levels of RA, retinol, and retinyl esters in the maternal system and their acquisition by the embryo, particularly during organogenesis in the mouse. Results indicate profound changes in maternal vitamin A levels during pregnancy in the mouse. These changes were characterized by a large, transient decrease in plasma retinol levels coincident with the period of organogenesis (e.g. gestational Days 9-14), and an apparent increase in mobilization from hepatic stores to the conceptus. During organogenesis, the embryo exhibited a steady increase in retinol levels with little increase in retinyl esters and virtually no change in RA. Analysis of retinoid accumulation patterns in the embryonic liver indicate that functional onset of vitamin A storage occurs by mid-organogenesis. In contrast, placental levels of these retinoids remained unchanged throughout organogenesis. Analysis of the conceptus as a developmental unit revealed that during early organogenesis the majority of retinoids are contained in the placenta (8-fold more than in the embryo). However, by mid-organogenesis the retinoid content of the embryo exceeds that of the placenta. Together, these results provide evidence that pregnancy in the mouse is accompanied by pronounced alterations in maternal retinoid homeostasis that occur coincident with the period of high embryonic sensitivity to exogenous retinoids. PMID- 1591337 TI - Changes in surface antigens on preimplantation mouse embryos. AB - Changes in the expression of specific cell surface antigens on preimplantation mouse embryos were examined by immunocytochemistry. Embryos were recovered at various times during the preimplantation phase of normal pregnancy, and from pregnancies with experimentally induced delayed implantation, and were probed with a panel of monoclonal antibodies against murine leukocyte antigens. Antibodies directed against certain macrophage surface glycoproteins (i.e., Mac-2 and Mac-3) and those against lysosome-associated membrane glycoproteins (i.e., LAMP-1 and LAMP-2) reacted specifically with cell surface determinants on the embryos. Differences in the spatiotemporal patterns of antibody binding during normal and delayed implantation indicate that expression of the antigenic determinants recognized by these antibodies is regulated individually in response to intrinsic as well as extrinsic signals at the time of implantation, and thus they may be important for the process of embryo implantation. PMID- 1591338 TI - In vitro prostaglandin release from and platelet-activating factor accumulation in isolated endometrial cells from pregnant and pseudopregnant rabbits. AB - Prostaglandin (PG) release from and platelet-activating factor (PAF) accumulation by enzymatically isolated endometrial epithelial and stromal cells from Day 6 pregnant and Day 6 pseudopregnant rabbits were studied in vitro, using RIA for PG measurement and a platelet aggregation assay for PAF measurement. On the first day of culture in serum-free media, PGF release into the medium was significantly higher from epithelial cells from Day 6 of pregnancy than from stromal cells from Day 6 of pregnancy or pseudopregnancy. PGE release did not differ significantly among these cell types. The addition of indomethacin (10(-5) M) to similar cultures inhibited release of both PGs from both cell types, but to a much greater extent from stromal than from epithelial cells. Significant stimulation of PG release by A23187 was achieved under all conditions on the fifth day of culture; PGE release was significantly greater than PGF release from stromal cells from Day 6 of pregnancy and pseudopregnancy, and release of both PGs from stromal cells was significantly greater from Day 6 of pregnancy than from Day 6 of pseudopregnancy. PG release from similar cells, cultured in medium containing 10% calf serum, was highest on the first or second day of culture and then, especially for PGF, declined with continued culture. PGE release was significantly higher than PGF release from stromal cells on the third and fourth days of culture. The ratios of PGF/PGE release from epithelial cells were significantly higher than those from stromal cells over the 5-day culture period for both reproductive stages. These ratios indicate the differential release of PGE and PGF from rabbit endometrial cell subpopulations and indicate a preferential release of PGE from stromal and of PGF from epithelial cells. Under basal conditions, PAF was not detected in epithelial or stromal cells cultured for 2 or 4 days, or in the associated culture media. If PAF had been released into the medium, it would have rapidly metabolized. Short exposure to calcium ionophore A23187 (10(-5) M) was able to stimulate PAF accumulation in epithelial and stroma cells in serum-free media, probably via the remodeling pathway. PAF was not detected in the medium. Intracellular PAF accumulation after exposure to A23187 (10(-5) M) for 5 min was significantly greater on the second day of culture than on the fourth day in epithelial and stromal cells from Day 6 of pregnancy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1591339 TI - Bovine placental progesterone synthesis: comparison of first and second trimesters of gestation. AB - We have previously reported that dispersed caruncle cells from cows during the first trimester of pregnancy, in comparison to caruncle cells from cows of more than 90 days of gestation, produce little progesterone (P4) and are refractory to agents that enhance steroidogenesis. To explain this refractoriness of the first trimester cells, we determined (1) the expression of cytochrome P450 side-chain cleavage (P450scc) and its mRNA, (2) the expression of adrenodoxin, and (3) 3 beta-hydroxysteroid dehydrogenase activity. We first determined P4 and pregnenolone (P5) production by dispersed caruncle cells from the two gestation periods using RIA. It was found that P4 synthesis by bovine maternal caruncle cells was low or undetectable in the first trimester but increased more than 10 fold in the second trimester of gestation. Addition of 25-OH-cholesterol (5 micrograms/ml) to second-trimester maternal cells increased P5 production, but no effect was observed in first-trimester cells. With [3H]P5 used as substrate, analysis of metabolites on thin-layer chromatography indicated that first trimester maternal cells synthesized a small amount of P4 (3.02% of total radioactivity) compared to second-trimester cells (16.4%). A readily detectable amount of 17 alpha-OH-P5 was produced by the second-trimester cells (5.02%) but not by the first-trimester cells (0.6%). No other metabolites could be characterized (less than 0.5%). Cytochrome P450scc expression and its mRNA and adrenodoxin content were determined by use of Western blot or dot-blot techniques. Proteins and mRNA were detected in maternal tissues of first and second trimesters of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591340 TI - Maturation, fertilization, and development of dog oocytes in vitro. AB - Preovulatory oocytes were collected from ovaries of beagle bitches that had received superovulatory treatment. They were cultured in a modified Krebs-Ringer bicarbonate solution containing 10% fetal calf serum and 30 mg/L gentamicin sulfate for up to 72 h. About 32% of oocytes reached metaphase II by 72 h of culture. When these in vitro-matured oocytes were inseminated with ejaculated beagle spermatozoa that had been preincubated for 4 h, sperm penetration of the zona pellucida started about 1 h after insemination, and both male and female pronuclei were seen in the ooplasm at 8 h after insemination. At 18-20 h after insemination, oocytes were transferred to Whitten's medium and cultured for 76-78 h. The first cleavage was observed at 48 h after insemination, and 15 of 45 oocytes developed to the 2-8-cell stage. These results demonstrate that in vitro matured canine oocytes can be fertilized and develop to the 8-cell stage in vitro. PMID- 1591341 TI - In situ localization of spermatogenic cell-specific glyceraldehyde 3-phosphate dehydrogenase (Gapd-s) messenger ribonucleic acid in mice. AB - Northern blot analysis with a cDNA clone for mouse spermatogenic cell-specific glyceraldehyde 3-phosphate dehydrogenase (Gapd-s) previously identified transcripts in isolated round spermatids, but not in isolated pachytene spermatocytes, strongly suggesting that Gapd-s transcription first occurs in haploid germ cells. In the present study, in situ hybridization was carried out with a [35S]-labeled anti-sense RNA probe of Gapd-s to define more precisely the temporal expression and spatial distribution of Gapd-s mRNA in adult mouse testes. Gapd-s transcripts were not detected in spermatogonia, primary spermatocytes, secondary spermatocytes, or spermatozoa. However, they were abundant in round spermatids and condensing spermatids. Transcripts were not detected in somatic cells of the testis, in oocytes in pre-antral or antral follicles, or in skeletal muscle. Grain counts were used to define when the Gapd s gene was expressed during round spermatid development in adult mice. The number of silver grains first exceeded background levels in step 4-6 spermatids (early cap phase of spermiogenesis) and were high in step 7-15 spermatids (acrosome and elongation phases of spermiogenesis). However, they returned to background levels in step 16 spermatids, the final step of spermiogenesis in the mouse. In 20-day old juvenile mice, Gapd-s transcripts were first detected in round spermatids during the early cap phase of development. These observations confirmed that Gapd s mRNA is expressed during the post-meiotic phase of male germ cell development, demonstrated that Gapd-s transcripts are present in step 4-15 spermatids, and established that transcription begins in round spermatids during the early cap phase of spermiogenesis in both juvenile and adult mice. PMID- 1591342 TI - The Sulawesi Crested Black Macaque (Macaca nigra) menstrual cycle: changes in perineal tumescence and serum estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone levels. AB - Events in the normal menstrual cycle of the endangered Sulawesi Crested Black Macaque (Macaca nigra) were characterized. Daily blood samples were obtained during 10 menstrual cycles from five M. nigra demonstrating regular cycles. The amount of perineal tumescence was scored daily. Serum levels of estradiol and progesterone were determined by RIA, serum LH levels were determined by the mouse Leydig cell bioassay, and serum FSH levels were determined by the rat granulosa cell aromatase bioassay. Cycle length was 39.8 +/- 1.0 days (mean +/- SEM) with an LH surge occurring 25 +/- 1.5 days from the onset of menses. After menses, both LH and estradiol were initially depressed, with estradiol first exceeding 50 pg/ml 8 days before the LH surge. In five cycles, peak estradiol levels (340 +/- 44 pg/ml) occurred on the day of the LH surge (637 +/- 58 ng/ml) and in the other five cycles, on the day before the LH surge. There was a broad increase of FSH in midcycle without a well-defined surge corresponding to the LH surge. Progesterone began increasing on the day of the LH surge and reached peak levels (6.8 +/- 0.96 ng/ml) 8 days later. Maximal perineal tumescence was generally associated with the time of the LH surge, but variation between animals made it impossible to predict accurately the day of the LH surge by perineal tumescence scores alone. PMID- 1591343 TI - Mating stimulates estradiol production by ovaries of the musk shrew (Suncus murinus). AB - Asian musk shrews (Suncus murinus) are induced ovulators, but exhibit no cyclic changes in reproductive structures or in sexual behavior. Mating behavior is induced by contact with a male. To determine if mating induces changes in ovarian steroidogenesis, ovaries removed from unmated animals and at 3, 10, 15, and 36 h after mating were cultured for 4 h in the presence or absence of gonadotropins (LH + FSH, 1 microgram/ml). Histological analysis revealed no obvious changes in follicular size or appearance at the end of culture in ovaries cultured at 3 and 10 h post-mating, as compared with ovaries from unmated shrews, and mating did not stimulate any discernable changes in steroid secretion in these two groups. However, at the end of the culture period, ovulation had occurred or was occurring in ovaries from 35% of the animals ovariectomized at 15 h after mating, and corpora lutea (CLs) were present in 39% of ovarian pairs obtained 36 h after mating. At 15 h post-mating, ovaries with ovulations secreted three times more estradiol than did ovaries that showed no evidence of stimulation by mating, but there were no differences in testosterone or progesterone production. In contrast, ovaries isolated 36 h post-mating with CLs secreted dramatically more of all three steroids than ovaries without CLs (23, 13, and 52 times more estradiol, testosterone, and progesterone, respectively). These data are consistent with plasma concentrations of estradiol at the time of ovariectomy, which were twice as high at both 15 and 36 h after mating, in animals whose ovaries showed evidence of ovarian stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591344 TI - Developmental changes of serum thymosin alpha 1 and beta 4 in male and male castrated pigs: modulation by testosterone and human chorionic gonadotropin. AB - Thymic secretory peptides thymosin beta 4 and alpha 1 have possible endocrine roles in both immune and reproductive systems; thus, they should respond to endocrine feedback control mechanisms consistent with gonadal function. In an initial experiment, male pigs (boars; n = 90; 10/time) were bled at 1, 3, 6, 12, 18, 24, 30, 36, and 96 wk of age before and 24 h after hCG stimulation. Thymosin beta 4 concentrations were significantly depressed 24 h after hCG challenge. Testosterone concentrations increased with age up to 36 wk and were further increased with hCG stimulation (p less than 0.01). In a subsequent experiment, boars (n = 12) and barrows (males castrated shortly after birth; n = 12) were blood-sampled, administered hCG, and sampled again 24 h later at 1, 3, 6, 12, 18, and 24 wk of age. Barrows (n = 12) were administered testosterone with the same protocol. Testosterone concentrations increased in boars with maturity and were further increased from the hCG stimulation (p less than 0.01). Thymosin beta 4 concentrations decreased with age in boars and barrows (p less than 0.01), and hCG challenge depressed thymosin alpha 1 and beta 4 concentrations in boars and thymosin beta 4 in barrows (p less than 0.01). Testosterone treatment of barrows also depressed thymosin beta 4 and alpha 1 in barrows (p less than 0.01). The depression of thymosins by hCG treatment points to a role for gonadotropins in altering circulating thymosin concentrations independent of, but in conjunction with, the effect of gonadal steroids. PMID- 1591346 TI - Qualitative characterization of oligosaccharide chains present on the rat zona pellucida glycoconjugates. AB - Zona pellucida (ZP), the extracellular glycocalyx surrounding the mammalian oocyte, is believed to mediate species-specific sperm-egg interaction. Despite numerous studies on characterization of ZP glycoconjugates in several species, little or no information is available on the number and chemical nature of the various components of the rat ZP. In this study we have attempted the biochemical characterization of the rat ZP using endo- and/or exo-glycohydrolases. Intact eggs from superovulated rats were radioiodinated by the chloramine-T method, and the labeled ZP components were resolved on SDS-PAGE under nonreducing conditions. These studies show that the rat ZP consists of three components with apparent molecular masses of 205 kDa (ZP1), 119 kDa (ZP2), and 115 kDa (ZP3). Unlike mouse ZP2 and ZP3, which resolve as distinct components on SDS-PAGE, rat ZP2 and ZP3 show substantial overlap in their molecular sizes and isoelectric points. Treatment of the rat ZP components with exo- (neuraminidase and alpha-L fucosidase) and/or endo- (endoglycosidase H, endoglycosidase F, N-glycanase, and O-glycanase) glycohydrolases indicated the following: 1) Both rat ZP2 and ZP3 contain N-linked oligosaccharide (OS) units as indicated by their sensitivity to endoglycosidase F and N-glycanase. 2) Treatment with N-glycanase caused a reduction in size of the rat ZP2 and ZP3 components by nearly 50% and 60%, respectively, indicating that the two ZP components are highly glycosylated. 3) Rat ZP3 was sensitive to O-glycanase, suggesting that this ZP component contains O-linked OS unit(s). 4) No evidence was obtained for the presence of fucosyl or sialyl residue(s) on the O-linked OS unit(s) of rat ZP3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591345 TI - Regulation of pulsatile gonadotropin secretion by estrogen, inhibin, and follistatin (activin-binding protein) in ovariectomized rats. AB - The following study was conducted to examine the effects of estrogen and polypeptides, given either alone or in combination, on pulsatile gonadotropin secretion. One week after ovariectomy, rats received s.c. injections of oil or various doses (0.5, 5, 20 micrograms) of estradiol benzoate (EB) followed 1 day later by i.v. administration of 60 micrograms purified porcine follistatin, 10 micrograms recombinant inhibin, or the appropriate vehicle. Four hours after injection of the nonsteroids, blood was collected at 10-min intervals for 2 h, and the effects on pulsatile hormone release were assessed. Administration of EB alone dose-dependently suppressed mean and trough (lowest point between two pulses) FSH levels and all parameters of pulsatile LH release. Both follistatin and inhibin at the doses employed suppressed mean FSH levels to an equivalent extent (40%). Follistatin, but not inhibin, suppressed FSH pulse amplitude, while neither polypeptide alone influenced FSH pulse frequency or any parameter of pulsatile LH release. The effects of follistatin and EB on mean FSH levels were additive at all EB doses, whereas the effects of inhibin and EB were additive only at the middle EB dose. Follistatin in combination with the lowest EB dose significantly suppressed mean LH levels. These studies are the first to demonstrate that combined treatment with estrogen and the nonsteroids follistatin and inhibin is more efficacious in suppressing FSH release than treatment with either agent alone, thereby indicating that both steroids and nonsteroids are probably important in the physiological regulation of FSH secretion in rats. The additive effects of these compounds on FSH secretion could form the basis for exploring novel contraceptive interventions. PMID- 1591347 TI - Systemic but not intraovarian concentrations of insulin-like growth factor-I are affected by short-term fasting. AB - To determine whether systemic and/or intraovarian concentrations of insulin-like growth factor-I (IGF-I) are affected by short-term fasting, 24 heifers were blocked by weight and, within block, were assigned to one of three treatments: fasted for 0 h (controls; n = 8), fasted for 24 h (n = 8), or fasted for 48 h (n = 8). Blood plasma was collected every 8 h from -64 h to 0 h before ovariectomy (OVEX). OVEX was performed per vagina under local anesthesia during the follicular phase of an estrous cycle (36-42 h after synchronization with prostaglandin-F2 alpha). Follicular fluid (FFL) and granulosa cells were collected individually from follicles greater than or equal to 6 mm (large), and FFL was pooled from follicles 1.0-5.9 mm (small) in diameter. Fasting did not affect (p greater than 0.20) the number (mean +/- SE) of small (52 +/- 7) or large (1.5 +/- 0.4) follicles per heifer, specific binding of 125I-hCG to granulosa cells of follicles greater than or equal to 8 mm in diameter, or concentrations of progesterone in FFL of small follicles. At OVEX, body weight was less (p less than 0.01) for 24 h- and 48 h-fasted heifers (412 +/- 7 kg and 399 +/- 7 kg, respectively) than for 0 h-fasted heifers (442 +/- 7 kg). At OVEX, plasma concentrations of IGF-I were lower (p less than 0.05) in the 48 h-fasted group (105 +/- 8 ng/ml) than in the 0 h-fasted group (140 +/- 8 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591348 TI - Adverse effects of cyclophosphamide on progeny outcome can be mediated through post-testicular mechanisms in the rat. AB - Previous studies from our laboratory have suggested that, in addition to an effect on spermatozoa in the testis, cyclophosphamide may have an adverse effect on spermatozoa after they leave the testis, during epididymal transit. To elaborate on this post-testicular effect on germ cells and to determine at which site(s) in the epididymis germ cells are most sensitive to cyclophosphamide treatment, three experiments were undertaken. First, the time course of the effect of treatment of male rats with cyclophosphamide on the outcome of their progeny was determined. Male rats were treated daily by gavage with saline or one of two doses of cyclophosphamide (6.8 mg/kg or 10.0 mg/kg) for 1, 4, or 7 days. At the end of each treatment period, males were mated to assess the effect on pregnancy outcome. No effect was observed on pre-implantation loss at any time among any of the groups, but there was a time-dependent and dose-related increase in post-implantation loss. Post-implantation loss was significantly increased after 4 days of treatment and reached nearly 40% after 7 days of drug exposure (10.0 mg/kg). Second, the effect of treatment with single high doses of cyclophosphamide was studied. Male rats were treated with a single dose of cyclophosphamide (10, 30, or 70 mg/kg) and bred 1 day and 4 days post-treatment. No significant change in pre-implantation loss was observed at either time point; no change in post-implantation loss was found after 1 day post-treatment. However, a significant increase in post-implantation loss was observed in the two high-dose groups 4 days post-treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591349 TI - Epidermal growth factor receptors in porcine endometrium: binding characteristics and the regulation of prostaglandin E and F2 alpha production. AB - Epidermal growth factor (EGF) and its receptor have been implicated in the control of uterine cell growth and differentiation. The objectives of this study were to determine EGF binding characteristics and effects of EGF on prostaglandin (PG) production in vitro by glandular and stromal cells from porcine endometrium. Endometrial tissues were taken from 10 sows on Day 13 of pregnancy (first day of estrus = Day 0). Glandular and stromal cells were separated by enzymatic dispersion and sieve filtration and cultured for 3 days. EGF-binding assay was carried out at 20 degrees C in the presence of 0.2 nM 125I-EGF with increasing concentrations of unlabeled EGF (0-12 nM). Scatchard analyses revealed one class of high-affinity binding sites in each cell type with apparent equilibrium dissociation constants (n = 6) of 2.96 +/- 0.60 nM and 2.48 +/- 0.50 nM for stromal and glandular cells, respectively. The apparent binding capacities were 199.3 +/- 34.8 fmol/10(6) cells for stromal cells and 40.7 +/- 6.5 fmol/10(6) cells for glandular cells. Effects of EGF on PG production were determined by including 1, 5, 10, or 20 ng/ml EGF in the medium for the final 24 h of the 72-h culture. EGF increased PGE (p less than 0.01) and PGF2 alpha (p less than 0.05) secretion by stromal cells. The highest concentration (20 ng/ml) of EGF increased secretion of PGE and PGF2 alpha by 133% and 64%, respectively, over controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591350 TI - Molecular and developmental studies of a sperm acrosome antigen recognized by HS 63 monoclonal antibody. AB - A conserved mouse sperm antigen (MSA-63) recognized by a monoclonal antibody (HS 63) was isolated from mouse testes by single-step immunoaffinity chromatography. Isolated MSA-63 preparation was shown to be a group of proteins ranging from 24 84 kDa and with isoelectric points (pIs) ranging from 4.0-6.0 when analyzed by two-dimensional (2-D) gel electrophoresis. Microsequencing techniques were employed to determine the relationships of various protein spots on 2-D gels. Partial amino acid sequences of some protein spots in isolated MSA-63 preparation were shown to be homologous to mouse actins, while others revealed homology only to the SP-10 protein. Rabbit antisera raised against isolated MSA-63 antigen preparation were used to immunoscreen a mouse testis cDNA library. Isolated cDNA clones carrying a 1.2-kb insert were used to obtain nucleotide sequences containing open-reading frames and to deduce the corresponding amino acid sequence of MSA-63. A high degree of homology was observed between MSA-63 and a known human sperm antigen, SP-10, at DNA/protein levels. Amino acid sequences of tryptic peptides derived from protein spots of 24-47 kDa and pIs of 4.2-4.4 were found to be identical to those deduced from isolated cDNA clones. The gene expression of MSA-63 during spermatogenesis in mice was studied using a specific cDNA probe as well as HS-63. It was observed that MSA-63 was not expressed until the postmeiotic stages of spermatogenesis. PMID- 1591351 TI - Evidence for binding and action of growth hormone in trout testis. AB - Growth hormone (GH) binding to testis tissue and GH action on trout testicular cells were studied in vitro. Labeled salmon GH (sGH) was able to bind to a trout testis membrane preparation. Binding sites showed high affinity (Ka = 1-2 x 10(9) M-1) and low capacity (11 fmol/g fresh tissue) for 125I-sGH. Salmon GH and bovine GH, but not salmon gonadotropin, could compete with 125I-sGH for site occupancy. The binding characteristics were similar to those of trout liver GH receptors that we previously described. Salmon GH (0.1 and 1 microgram/ml) and bovine GH (10 micrograms/ml) could modulate steroidogenesis in cultured testicular cells: 17 alpha-hydroxy, 20 beta-dihydroprogesterone (17 alpha 20 beta OHP) accumulation in culture medium was stimulated by GH addition, and this effect increased with duration of culture and/or stimulation; 11-ketotestosterone accumulation tended to be inhibited in the presence of GH at the beginning of culture. These effects were dependent on GH concentration and were observed both in the absence and presence of gonadotropin. The amplitude of the sGH effect varied between experiments, probably according to the physiological state of the cells used. In vivo, GH and 17 alpha 20 beta OHP plasma levels increased at the beginning of spermiation (sperm production) and decreased at the end of spermiation. This relationship suggests that, at the end of the reproductive cycle, high GH levels are associated with the production of 17 alpha 20 beta OHP, a progestin necessary for efficient spawning in this species. We conclude that GH may play a role in testicular physiology, at least at certain stages of spermatogenesis. PMID- 1591352 TI - Effects of three methods of selection for litter size in mice on pre-implantation embryonic development. AB - Characteristics of preimplantation embryonic development to Day 3.5 of gestation were evaluated in lines of mice after 21 generations of selection for litter size or components of litter size. Selection criteria were direct selection for number born (LS), selection on an index of ovulation rate and the proportion of ova shed that resulted in fully formed pups (IX), selection for number born in unilaterally ovariectomized females as an indication of uterine capacity (UT), and an unselected control (LC). Comparison of the average distributions of embryonic stage of development on the left side of the uterus showed that selection (average effect of LS, IX, and UT vs. LC) tended to advance (p = 0.07) the average stage of embryonic development at Day 3.5 and shift the distribution (p = 0.10) by increasing the frequency of expanded blastocysts and decreasing the frequency of pre-morula embryos. A similar shift in the distribution on the right side of the uterus was not statistically significant. Selection decreased (p = 0.06) variability in developmental stage among embryos within the right uterine horn. These selection criteria evaluated in the mouse appear to have changed the frequencies of genes that affect some determinants of average stage of embryonic development and uniformity of development within a uterine horn at Day 3.5 of gestation. PMID- 1591353 TI - Effect of nutritional repletion on pituitary and serum follicle-stimulating hormone isoform distribution in growth-retarded lambs. AB - Using nutritionally restricted ovariectomized lambs, we tested the hypothesis that nutritionally regulated endogenous increases in GnRH secretion (as assessed by LH pulsatility) not only alter the quantity of FSH present in the pituitary and serum, but also alter the pituitary and serum FSH isoform distribution. Eleven lambs were nutritionally restricted from weaning and ovariectomized at 12 wk of age. Beginning at 56 wk, 6 were fed ad libitum for 14 days, and the other 5 were continued on the restricted diet. Jugular blood samples were collected frequently (12-min interval) for 4 h prior to pituitary removal. Immunoreactive ovine LH (I-oLH) and immunoreactive ovine FSH (I-oFSH) concentrations were measured in sera and pituitary extracts. Bioactive (B) oFSH and I-oFSH isoform distribution patterns were determined in serum pools and pituitary extracts. Ad libitum feeding increased I-oLH pulsatility and mean concentrations of pituitary and serum I-oFSH and B-oFSH. The I-oFSH isoform distribution patterns in the pituitaries from the nutritionally restricted animals were not different from those of repleted lambs; in both, the predominant FSH peak eluted in the pH range of 3.5-5.6. A similar predominance of I-oFSH isoforms was also evident in the serum of ad libitum-fed animals. This predominance was not demonstrable in 3 of the restricted-fed animals due to low circulating concentrations of FSH (less than 2.5 ng/ml). Subsequent studies, utilizing serum from 4 additional restricted fed lambs with circulating I-oFSH concentrations in the range of 4-14 ng/ml (but no detectable LH pulses) revealed similar predominance of oFSH isoforms in the pH 3.5-5.6 range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591354 TI - Influence of gonadotropin treatment interval on follicular maturation, in vitro fertilization, circulating steroid concentrations, and subsequent luteal function in the domestic cat. AB - The impact of the eCG-hCG interval on in vitro fertilization (IVF), endogenous hormonal patterns, and luteal integrity was studied in the domestic cat. Adult cats with inactive ovaries were given eCG (i.m.) and then hCG (i.m.) 80, 84, 88, 92, or 96 h later. Oocytes were aspirated 25-27 h after hCG and co-cultured with swim-up-processed cat spermatozoa. Blood samples were collected daily from 2 days before eCG treatment (Day -2) through Day 14, and sera were analyzed for estradiol-17 beta and progesterone. The mean number of oocytes recovered from the 80-92-h groups (range, 17.2 +/- 2.1 to 21.1 +/- 3.0) did not differ (p greater than 0.05); however, oocyte number was reduced (p less than 0.05) in the 96-h group (10.3 +/- 2.1). The proportion of all oocytes classified as mature was greater (p less than 0.05) when hCG was given 80, 84, or 88 h compared to 92 or 96 h after eCG. Delaying hCG treatment until 96 h caused more than 25% of all oocytes to degenerate, which was a greater rate (p less than 0.05) than in all other groups. The IVF rate at 80 (57.1%), 84 (56.5%), 88 (65.0%), and 92 (52.5%) h was greater (p less than 0.05) than that observed at 96 h (33.6%). Circulating estradiol-17 beta concentrations began to rise above nadir within 24 h of eCG injection in all interval groups. On the basis of areas under the curve, cats in the 80- and 84-h treatments produced more (p less than 0.05) estradiol-17 beta than other groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591355 TI - Interactions of human sperm acrosomal protein SP-10 with the acrosomal membranes. AB - The interaction of the human acrosomal protein SP-10 with the acrosomal membranes was analyzed by the ability of Triton X-114 (TX-114) and other agents to release SP-10 from the acrosome. Treatment of human sperm with TX-114 revealed a pool of SP-10 that was released by TX-114 and a pool of SP-10 that was TX-114-resistant. TX-114-resistant SP-10 was associated with the equatorial segment and with TX-114 resistant portions of the acrosomal matrix and the inner acrosomal membrane. Phase partitioning of TX-114-released and TX-114-resistant SP-10 pools showed that both were hydrophilic, indicating that these pools consist of proteins that are peripherally associated with, rather than integral to, the acrosomal membranes. Sequential treatments of human sperm with various agents showed that repeated washes with TX-114 or 1.5 M NaCl had little or no effect on TX-114 resistant SP-10, whereas treatment with a chaotropic salt (150 mM sodium thiocyanate) and buffers at pH extremes (pH 2.0 and 10.0) completely released this pool of SP-10 from the acrosome. Together the results suggest that SP-10 is a hydrophilic peripheral acrosomal membrane protein that may be associated with a TX-114-resistant "anchor." PMID- 1591356 TI - Renal pain in polycystic kidney disease: when the hurt won't stop. PMID- 1591357 TI - Evolving role of growth factors in the renal response to acute and chronic disease. AB - The roles of growth factors in the pathogenesis of various forms of acute and chronic renal disease are largely putative. Nevertheless, there is a growing body of information that links specific growth factors to particular forms of renal injury. In all instances, it is supposed that such associations are not necessarily unique and that multiple cytokines probably interact to determine the pattern of injury or the regenerative response to such injury. Regeneration of tubular epithelium after acute tubular necrosis involves upregulation of the epidermal growth factor (EGF) receptor. Early studies of exogenously administered EGF indicate that the severity and duration of renal failure may be attenuated by this growth factor. Thus far, the observed responses have been limited and the role of EGF as a therapeutic agent requires more study. The mechanism of generation of tubulointerstitial injury in most forms of renal disease is difficult to understand. Early in vitro studies of growth factor production by tubular cells (in the absence of any infiltrating cells) indicate that platelet derived growth factor produced by the medullary collecting duct is mitogenic for renal medullary fibroblasts, suggesting a paracrine growth system in this region of the kidney. Insulin-like growth factor I has also been shown to be produced by collecting duct cells. Its production is increased by EGF, and its association with certain forms of renal hypertrophy, i.e., diabetes and hypersomatotrophic states, implies its participation in the hypertrophic growth response. Platelet derived growth factor is a potent mitogen for glomerular mesangial cells, and its production is regulated by a variety of cytokines.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591358 TI - Progression of chronic renal failure on substituting a ketoacid supplement for an amino acid supplement. AB - Twelve patients with severe chronic renal failure (average initial GFR, 13 mL/min) were monitored for 4 to 23 months while receiving an essential amino acid supplement and were then switched to a ketoacid supplement for 6 to 40 months, while continuously receiving a very low-protein (0.3 g/kg), low-phosphorus (7 to 9 mg/kg) diet. Urinary urea N excretion indicated that actual dietary protein intake averaged 0.46 g/kg. Progression, estimated as the linear regression slope of radioisotopically determined GFR on time, slowed from -0.46 +/- 0.31 (SD) to 0.24 +/- 0.15 mL/min/month (P = 0.029). Serum urea N, creatinine, phosphate, and uric acid rose significantly as GFR fell; blood pressure, plasma lipids, and urinary urea excretion were unchanged. Urinary 17-hydroxy-corticosteroid excretion decreased 18%, but this change was only marginally significant (P = 0.087). There was no change in plasma or urinary cortisol or urinary aldosterone. Viewed in light of previous evidence that progression seldom slows when treatment remains constant, the results suggest that this ketoacid supplement slows progression by approximately half, compared with an essential amino acid supplement, with no change in diet. PMID- 1591359 TI - Spontaneous changes in the rate of decline in reciprocal serum creatinine: errors in predicting the progression of renal disease from extrapolation of the slope. AB - The slope of reciprocal serum creatinine (1/Pcr) versus time has been used to measure the rate of progression of chronic renal disease, predict the interval until onset of end-stage renal disease, and assess the effect of therapy. In order to determine the errors that might result from extrapolating the slope of 1/Pcr versus time beyond the interval of observation, we applied a method of linear regression analysis to search for spontaneous changes in slope in 21 patients from New England Medical Center and 56 patients in three published studies in whom the decline in 1/Pcr appeared constant (r greater than or equal to 0.84 for the correlation of 1/Pcr versus time). Significant changes in the slope (breakpoints) were identified in one third to one half of the 77 patients and appeared to be spontaneous. The second slope was less steep in 49 patients (6.1%); the mean value for serum creatinine at the time of the breakpoint was 5.3 mg/dL; the mean change in slope (absolute value) was 0.005 dL/mg/month (adults) and 0.017 dL/mg/month (children); and the mean error in prediction of the interval until the final value for serum creatinine was 27% of the actual interval. We conclude that spontaneous breakpoints in the slope of 1/Pcr versus time are very frequent, even among patients with an apparent constant rate of decline. Breakpoints may cause errors in extrapolating the slope to predict the interval until the onset of end-stage renal disease and to assess the effect of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591360 TI - Specificity of basolateral organic anion exchanger in proximal tubule for cellular and extracellular solutes. AB - We used an epifluorimetric technique to study the mechanism of organic anion transport across the basolateral surface of isolated S2 segments of rabbit proximal tubules. Fluorescein influx and efflux rates across the basolateral surface of lumen-collapsed tubules were determined from serial measurements of cellular fluorescein content after its addition to or removal from the bathing medium. We examined the effect on fluorescein transport of monocarboxylic and dicarboxylic metabolic intermediates added to the bathing medium or preloaded into the cells. The presence of the monocarboxylates (octanoate, valerate, butyrate, propionate, and acetate) in the bathing medium inhibited fluorescein influx. The eight-carbon-chain fatty acid, octanoate, was nearly as potent an inhibitor as probenecid and was more potent than p-aminohippurate (PAH) (IC50 = 10, 6, and 141 microM, respectively); the shorter chain fatty acids were much less effective (IC50 greater than or equal to 1,000 microM). The dicarboxylates (succinate, adipate, and alpha-ketoglutarate) moderately inhibited fluorescein influx (IC50 = 505, 245, and 257 microM, respectively). To determine the effect of intracellular organic anions on fluorescein influx, tubules were preincubated with organic anions to load the cells; the compounds were then removed from the bath, and fluorescein influx was measured. Preincubation with monocarboxylates, octanoate, butyrate, acetate, and PAH had no effect. In contrast, the dicarboxylates alpha-ketoglutarate, glutarate, and adipate stimulated fluorescein influx by 58, 53, and 43%, respectively, but succinate had no effect. Fluorescein efflux was accelerated by medium octanoate, PAH, alpha-ketoglutarate, and succinate but not by acetate. Probenecid alone had no effect on fluorescein efflux, but it blocked the stimulation caused by medium PAH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591361 TI - Tubular resistance to furosemide contributes to the attenuated diuretic response in nephrotic rats. AB - A blunted response to loop diuretics frequently occurs in nephrotic syndrome (NS). Observations that nephrotic humans have reduced sodium excretion at normal rates of diuretic excretion have suggested that tubular resistance to the drug may contribute to diuretic resistance. To determine if tubular resistance to furosemide exists in NS, late proximal and early distal tubular micropuncture was performed in rats with puromycin aminonucleoside-induced NS and in control rats after an i.v. bolus dose of furosemide of 1 mg/kg body wt. Absolute and fractional urinary sodium excretions were less (P less than 0.05) in NS rats than in control rats after furosemide. Inulin clearance and total urinary furosemide excretion, however, were not different between groups. Thus, similar to reports in humans, the urinary sodium-to-furosemide excretion ratio was less (P less than 0.05) in NS than in control rats. Single-nephron GFR and chloride delivery to late proximal sites were not different between groups after furosemide. In contrast, absolute and fractional chloride deliveries to early distal sites were less (P less than 0.05) in NS rats after furosemide. Calculated loop chloride reabsorption after furosemide was greater (P less than 0.05) in NS than in control rats when expressed either as percentage of filtered load (39.4 +/- 3.1 versus 28.2 +/- 2.0%) or delivered load (67.9 +/- 4.7 versus 48.3 +/- 3.0%). Loop fluid reabsorption was not different between groups. Thus, loop chloride reabsorption is inhibited to a lesser extent by i.v. furosemide in NS than in normal rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591362 TI - Cyst decompression surgery for autosomal dominant polycystic kidney disease. AB - A prospective study was undertaken to evaluate the efficacy of surgical cyst decompression for retarding the progression of renal failure and for the management of chronic pain associated with autosomal dominant polycystic kidney disease (ADPKD). Thirty patients with ADPKD and pain (14 patients), renal insufficiency (4 patients), or both (12 patients) underwent unilateral (19 patients) or bilateral (11 patients) cyst reduction surgery. The patients were monitored for 21 +/- 2 months postoperatively. The probability of being painfree was 80% at 1 yr and 62% at 2 yr. Preoperative and 1-to 3-month postoperative serum creatinine levels and GFR (clearance of insulin or (125I) iothalamate) were not significantly different (2.2 +/- 0.3 versus 2.2 +/- 0.3 mg/dL and 49 +/- 8 versus 54 +/- 9 mL/min/1.73 m2, respectively). One-year serum creatinine levels remained unchanged in patients with normal preoperative renal function (1.0 +/- 0.07 versus 1.0 +/- 0.05 mg/dL), whereas those with preoperative progressive renal insufficiency had no difference in the mean slope of reciprocal serum creatinine plots preceding and after surgery (-0.008 +/- 0.001 versus -0.009 +/- 0.002 dL/mg/month). In patients who underwent unilateral surgery, split function isotope scans showed no change in function of the operated kidney when compared with the nonoperated kidney. Surgical cyst decompression provides effective relief of chronic pain without compromising renal function. However, the data in this article do not support the use of this procedure to slow progression of renal insufficiency in ADPKD. PMID- 1591363 TI - Nephrologists' experience with and attitudes towards decisions to forego dialysis. The End-Stage Renal Disease Network of New England. AB - Ethicists and lawyers agree that competent adult patients or their surrogate decision-makers have the right to forego life-sustaining treatment, but the views of practicing physicians have not been well-studied. To examine nephrologists' experience with and attitudes towards decisions to forego dialysis, a questionnaire was sent to all 161 nephrologists performing chronic dialysis in six New England states; 118 (73%) responded. The proportion of nephrologists who reported withholding (not starting) dialysis from the cited numbers of patients during the previous year was 11%, 0; 58%, 1 to 5; 20%, 6 to 10; 8%, 11 to 15; and 3%, greater than or equal to 16. For withdrawing (stopping), the proportions were 19%, 0; 73%, 1 to 5; 9%, 6 to 10; and 0%, greater than or equal to 11. The nephrologists withheld dialysis more times than they withdrew it (chi 2 = 26; P = 0.004). If requested to do so by a competent patient, 88% of nephrologists would stop dialysis. If requested by the family of an incompetent patient, 90% would stop if the patient had clear prior wishes, but only 63% would stop if prior wishes were unclear. With competent patients, the issue of withdrawal of dialysis was usually raised by the patient (56%). With incompetent patients, the issue was raised by the family (42%) or nephrologist (30%). It was concluded that decisions to withhold dialysis are more frequent than decisions to withdraw it. Moreover, nephrologists agree about the management of requests to withdraw dialysis in competent patients or incompetent patients with clear prior wishes; they disagree about the management of incompetent patients with unclear prior wishes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591364 TI - Platelet-activating factor biosynthesis by cultured mesangial cells is modulated by proteinase inhibitors. AB - Rat mesangial cells stimulated with calcium ionophore A23187 and phagocytosis were shown to produce platelet-activating factor (PAF), a mediator of inflammation and endotoxic shock. In the study presented here, the cultured human mesangial but not epithelial cells synthetized PAF not only in response to calcium ionophore A23187 and phagocytosis of immunoglobulin G-coated latex beads, but also after stimulation with cytokines such as tumor necrosis factor-alpha and interleukin-1 beta. PAF synthetized after stimulation with A23187 and to a lesser extent with phagocytosis was partially released. In contrast, PAF synthesized by stimulation with tumor necrosis factor-alpha and interleukin-1 beta remained cell associated. Experiments with labeled precursors demonstrated that PAF was synthetized via the remodeling pathway that involves the activation of phospholipase A2 and of an acetyl-coenzymeA:2-lyso-PAF acetyltransferase. Synthetic inhibitors of serine proteases as well as plasma alpha 1-proteinase inhibitor inhibited the activation of phospholipase A2 detected as release of (14C) arachidonic acid and the activation of acetyl-CoA:2-lyso-PAF acetyltransferase at concentrations 100-fold lower than those present in plasma. This raises the question about the ability of mesangial cells to synthetize PAF in vivo. However, the inhibitory effect of plasma alpha 1-proteinase inhibitor may be abrogated by oxidative inactivation due to a concomitant stimulation of mesangial cell respiratory burst or in zones of close contact among cells or matrix, which have been shown to exclude antiproteinases. PMID- 1591365 TI - Selection of B cell clones and memory B cells. AB - During a humoral immune response, a variety of histological, cellular, and molecular changes occur within the immune system. In this review, we would like to summarize and integrate these changes with a view toward gaining insight into the process of clonal selection. We describe here how antigen receptor number limits the sensitivity of a B cell to transduce a signal in response to antigen. We have also seen that this limitation can be compensated for by expressing a higher affinity receptor for antigen. These data suggest that the down regulation of antigen binding receptors in germinal center cells might be designed to exploit anticipated increases in affinity that result from somatic hypermutation in these tissues. This hypothesis is consistent with observed biological changes that occur during an immune response and has bearing on both the mechanism of affinity maturation and generation of immunologic memory. PMID- 1591366 TI - In vivo retroviral marking of antigen-specific B lymphocytes. AB - A major obstacle in the study of B lymphocyte development subsequent to immunization has been the paucity of distinctive phenotypic markers which might permit the separation and scrutiny of a mature antigen-experienced or memory cell population. To address this issue, we have introduced a recombinant non replicating retrovirus into antigen-reactive lymph nodes in vivo using the expression of a reporter gene to monitor the trafficking, phenotype and persistence of retrovirus-marked B cells. Marked cells are first observed in the medullary cords where they proliferate for approximately 10 days prior to migration to the spleen. Up to half of the marked cells bear antigen-specific immunoglobulin receptors, but otherwise phenotypically resemble conventional B cells. The abundance and persistence of the marked cells suggest an association with the memory compartment. These experiments demonstrate a feasible approach for the identification and lineage analysis of antigen-responsive B cells, and suggest that the lymph node medulla supports a transient phase of post-antigenic B cell development associated with a long-lived antigen-specific B cell subset. PMID- 1591367 TI - The dynamics of immunological memory. AB - Memory has long been thought of as a stable phenomenon within the immune system: once generated it lasts for a very long time. This static view of immunological memory predicts that an established population of memory cells is independent of outside influences. Recent findings, concerning the population kinetics of the peripheral pool of lymphocytes and, more directly, concerning the influence of antigen on memory cell survival, are forcing us to reassess this idea. I present here a dynamic view of immunological memory which takes into account an immune system that appears in continual flux and whose constituent cells may rely upon recurrent signals for their survival. This view of memory also makes certain predictions and these are considered. PMID- 1591368 TI - The generation of memory B cells. AB - Immunization leads to the generation of antibody forming cells (AFC) and secondary B cells which differ substantially from primary B cells. Based on the function of the progeny of enriched precursor cell populations, naive progenitors of memory B cells have been separated from primary AFC precursors. Precursors of memory cells: (1) require multiple antigenic stimulations to generate antibody responses which are prolonged, of increased magnitude, and generated with rapid kinetics; (2) have the capacity to form germinal centers; (3) accumulate somatic mutations; (4) display repertoire similarities with secondary B cells; and (5) can be stimulated with cross-reactive antigens. The primary AFC precursors responded with characteristic primary responses. PMID- 1591369 TI - Chemotherapy for advanced malignant melanoma. AB - Systemic chemotherapy for the treatment of metastatic melanoma remains disappointing. Nor new single agent has demonstrated promising results. The combination of cisplatin, decarbazine, carmustine, and tamoxifen appears to be one of the most active regimens with an overall response rate approaching 50%. In some patients, responses have been durable and exceed 3 years. Sequential small phase II trials suggest that tamoxifen is an important component in this combination. The efficacy of the combination of hormonal and chemotherapy, however, needs to be corroborated in a large multicenter phase II trial. In addition, further laboratory and clinical studies are needed to evaluate the role of tamoxifen. Biological response modifiers, such as interleukin-2 and alpha interferon, have limited activity as single agents, but in combination with cytotoxic agents show some promise and merit further evaluation. Future research should focus on the development of more effective agents, and on the use of aggressive adjuvant and neoadjuvant chemotherapy in high-risk patients with locally advanced disease. PMID- 1591370 TI - The use of protein A columns in the treatment of cancer and allied diseases. AB - The staphylococcal cell-wall protein known as protein A has been explored as a therapeutic modality in the treatment of cancer and allied diseases. Protein A binds the Fc fragment of IgG 1, 2 and 4, and preferentially binds to IgG incorporated into immune complexes. Early investigators focused on the immune suppressive effects of immune complexes in cancer and, based on in vitro experiments, postulated that clearance of immune complexes in vivo would permit effective immune clearance of cancer cells. A large clinical trial of the perfusion of cancer patient plasma over protein A was subsequently undertaken. Results were generally disappointing, with no complete remissions and overall response rates of 22%. Response rates for Kaposi's sarcoma (39%) and breast adenocarcinoma (26%) were somewhat encouraging, and further clinical trials in these disorders are ongoing. More impressive have been the responses to protein A perfusion in immune thrombocytopenia and hemolytic-uremic syndrome. Using a protein A-silica device, Snyder et al. reported responses in 42% of immune thrombocytopenia patients, with mean increases in platelet count from 27 x 10(9)/l to 120 x 10(9)/l. On the basis of these results, the protein A-silica column was approved by the United States Food and Drug Administration for treatment of immune thrombocytopenia. Equally encouraging are reports of an overall 59% response rate in cancer chemotherapy-related hemolytic-uremic syndrome. Reported toxicities include fever, chills, hypotension, dyspnea and musculoskeletal pain. With rare exceptions, these reactions are easily treated and do not result in cessation of therapy. Unfortunately, the mechanism of action of plasma perfusion over protein A is very unclear.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591371 TI - Changes in the coagulation-fibrinolysis balance of endothelial cells and mononuclear phagocytes: role in disseminated intravascular coagulation associated with infectious diseases. AB - Over the last few years, evidence has accumulated that the pathogenetic mechanism of disseminated intravascular coagulation encountered in patients with infectious diseases is extraordinarily complex and involves multiple interactions between the microorganism itself and/or a number of mediators, both microorganism derived and host manufactured, and multifunctional cellular systems, namely endothelial cells and mononuclear phagocytes. In particular, infectious agents and mediators shift the coagulation-fibrinolysis equilibrium of these cells towards fibrin formation and accumulation, via enhancement of procoagulant properties and reduction of both anticoagulant and fibrinolytic capacities. New insights into the pathogenetic mechanism may have important implications for the management of infected patients with disseminated intravascular coagulation. PMID- 1591372 TI - Heat shock proteins in health and disease. AB - Heat shock proteins are among the most abundant proteins of the biosphere. They not only play a major role under stress conditions but also perform important physiological functions. The present review summarizes the potential contribution of heat shock proteins to health and disease related to immunity: their contribution to antibody assembly and antigen presentation; their role in host cell protection against "immune stress"; their participation in tumor surveillance; their relation to gamma/delta T-cell recognition; their function as microbial virulence factors; their dominant antigenicity for the immune response against microbial pathogens; and their possible role as autoantigens. The findings summarized here illustrate the marked liaison between heat shock proteins and the immune response, which may be both beneficial and detrimental to the host. PMID- 1591373 TI - Tissue-type plasminogen activator is involved in skeletal metastasis from human breast cancer. AB - This study was undertaken to determine if primary breast tumor plasminogen activator expression correlates with skeletal metastasis in breast cancer. Total plasminogen activator activity was significantly lower in tumors of patients with recurrence than in recurrence-free patients. Similarly, the primary tumors of patients with skeletal metastasis contained considerably less enzyme activity compared with those of patients surviving without skeletal metastasis. When patients with skeletal metastasis were categorized in terms of their recurrence pattern, those who had skeletal metastasis without other organ metastasis had significantly less tissue-type plasminogen activator antigen in their primary breast tumors than did those who had metastasis to other organs. Furthermore, a significantly lower level of tissue-type plasminogen activator antigen was found in primary tumors associated with axial bone metastasis than in those associated with appendicular bone metastasis. These results suggest that tissue-type plasminogen activator is involved in skeletal metastasis formation by its effects through the vertebral venous plexus. PMID- 1591374 TI - Immunogenicity of Haemophilus influenzae type b capsular polysaccharide and its tetanus toxoid conjugate in patients with recurrent infections or humoral immunodeficiency. AB - The antibody response to the capsular polysaccharide of Haemophilus influenzae type b was evaluated after vaccination with the capsular polysaccharide or its tetanus toxoid conjugate in 41 randomized patients with recurrent infections, IgA deficiency, common variable immunodeficiency, or the Wiskott-Aldrich syndrome. Serum antibodies were measured using a Farr assay for total antibodies and an enzyme-linked immunosorbent assay for antibodies of the three main immunoglobulin classes and of each IgG subclass. Antibody levels reached concentrations generally considered as protective in the majority of cases, the best response being observed after two injections of the conjugate vaccine with a 1-month interval. Vaccination with the conjugate therefore seems to be promising for the prevention of Haemophilus influenzae type b infections in such patients. PMID- 1591375 TI - Peripheral edema due to increased vascular permeability: a clinical appraisal. AB - The release of vasoactive substances produces reversible changes of endothelial permeability with consequent edematous syndromes. We present 899 patients referred to our clinic for "non-hydrostatic non-hyponcotic" recurrent edema problems. Personal and family histories were recorded and a complete physical examination was carried out for each patient. In chronic situations laboratory tests [blood cell count, cryoglobulins, thyroid hormones, complement components (C3, C4, C1 inhibitor), total IgE, skin testing] were performed. Four subgroups of angioedema are identified for relevant clinical and etiopathogenetic differences. Seventy-three percent of patients had an urticaria-angioedema syndrome responding to antihistamine and/or corticosteroid treatment (histamine dependent angioedema). Twenty-three percent had an angioedema related to a deficiency in C1 esterase inhibitor (complement-dependent angioedema). In a minority of patients, angioedema was due to the pharmacological effect of a drug (pharmacological angioedema) or was of a totally unknown origin (idiopathic angioedema). A generalized increase in vascular permeability was reported in 3 patients (systemic capillary leak syndrome). A brief survey of the literature is given with the review of our patients. PMID- 1591376 TI - Apolipoprotein B and A-I in relation to serum cholesterol and triglycerides in 43,000 Swedish males and females. AB - Automated methods for the determination of apolipoprotein B and apolipoprotein A I were developed, tested, and applied in screening programs of large populations to improve information about the composition and degree of hyperlipoproteinemia. Apolipoproteins B and A-I, total cholesterol, and triglyceride levels were measured in 25,659 males and 18,144 females between 20 and 79 years of age, the majority subjectively healthy. The immunoturbidimetric methods used for apolipoproteins B and A-I were shown to be stable over time, and the errors of the methods were below 7%. Apolipoprotein B correlated with total cholesterol (r = 0.86, P less than 0.001) for each age decile group and for both sexes (r = 0.82 0.87, P less than 0.001). For a subsample comparable to the large population, apolipoprotein B correlated with cholesterol in low density (i.e., the atherogenic particle), r = 0.89, P less than 0.001. The mean values for apolipoprotein B increased with age for both sexes, with much higher levels in males than in females under 50 years of age. Apolipoprotein A-I was lower in males than in females in all age-groups. At all cholesterol levels males had higher apolipoprotein B, and at the same triglyceride level, also lower apolipoprotein A-I and hence a higher B/A-I ratio than females. Using apolipoprotein B and A-I (high-density lipoprotein cholesterol) particles and adopting Swedish consensus criteria for the diagnosis of risk of ischemic heart disease, examples are given showing that many individuals, especially females, with high or borderline total serum cholesterol can be excluded from further investigation/treatment for hypercholesterolemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591377 TI - Cholesteryl ester transfer protein in human brain. AB - The evidence that apolipoproteins are found in the cerebrospinal fluid and low density lipoprotein receptor is found in the brain suggests that the brain may have an active lipid transport system. In plasma, cholesteryl ester transfer protein mediates the exchange and net transfer of cholesteryl ester and triglycerides among lipoproteins. Cholesteryl ester transfer activity was measured in the cerebrospinal fluid and plasma of ten neurologically normal subjects. Cholesteryl ester transfer activity was readily detectable in cerebrospinal fluid (7.4 +/- 13% cholesteryl ester was transferred per 20 microliters), and this activity was completely abolished with specific antibody against the plasma cholesteryl ester transfer protein. The concentration of cholesteryl ester transfer activity in the cerebrospinal fluid was about 12% of that found in plasma, whereas the concentration of albumin in cerebrospinal fluid was only about 0.6% of that in plasma, suggesting direct synthesis of cholesteryl ester transfer protein within the brain. Cholesteryl ester transfer activity was found in conditioned medium from human neuroblastoma and neuroglioma cells and sheep choroid plexus. The data suggest that cholesteryl ester transfer protein is synthesized and secreted in the brain. This protein could play an important role in the transport and redistribution of lipids within the central nervous system. PMID- 1591378 TI - DNA fingerprinting in leukemia. AB - The detection of polymorphic regions of the human DNA provides individual specific markers, DNA fingerprints (DNA-F), for the identification of individuals. DNA-F can also be used for the detection of cell clones and serve as molecular markers of malignant disease. In leukemia DNA-F analysis can be used for the follow-up studies during remission or after bone marrow transplantation. Recent studies on DNA fingerprinting in leukemia are reviewed. PMID- 1591379 TI - Higher cure rates in acute leukemia: now more probable with increasingly effective induction therapy. AB - Traditional therapy of acute myelogenous leukemia has not cured more than 10% of patients and, of acute lymphoblastic leukemia not more than 30% of adults. In part, this is due to the lack of agents effective enough to induce remissions of such quality that cure is possible. The introduction of mitoxantrone and its use in high dose with high-dose cytarabine for induction therapy, raises the possibility of an increased cure rate of acute myelogenous leukemia and acute lymphoblastic leukemia. PMID- 1591380 TI - Cytokine gene transfer in tumor cells as an approach to antitumor therapy. AB - The transfer of cytokine genes into cancer cells, resulting in cytokine release directly at the site of tumor growth, has proven effective in inhibiting tumor growth in the absence of any toxic effect. Some cytokines induce tumor suppression even in T-cell-deficient mice, suggesting their potential therapeutic effect in poorly immunogenic tumors; other cytokines induce memory T cells that protect mice from subsequent tumor injection. The effects of cytokine genes transferred into tumor cells are summarized and implications discussed. PMID- 1591381 TI - The critical role of interleukin-6, interleukin-1B and macrophage colony stimulating factor in the pathogenesis of bone lesions in multiple myeloma. AB - Lytic bone lesions and hypercalcemia are common features of multiple myeloma. In contrast, they are exceptional in other B-cell malignancies. Myeloma bone involvement is related to an uncoupling process associating increased osteoclastic resorption with decreased bone formation. Several osteoclast activating factors, such as interleukin-1, macrophage colony-stimulating factor, and interleukin-6, are involved in this process. However, interleukin-6, the major myeloma cell growth factor, plays a critical role in myeloma-induced bone resorption. PMID- 1591382 TI - Paraproteins in rheumatoid arthritis and related disorders. AB - There is evidence that the prevalence of monoclonal parparoteinaemia is slightly increased in patients with rheumatoid arthritis. The possibility that this may be a marker of the development of later malignancy in such patients is explored. Mortality rates in rheumatoid arthritis are increased although the development of lymphoreticular malignancy contributes only a small percentage of this increase. However, it does seem likely that patients with longstanding severe rheumatoid arthritis are more at risk of developing myeloma or lymphoma if they have a monoclonal paraprotein band in their serum. IgA paraprotein seems to carry a higher risk than IgG whilst other factors such as urinary free light chains and the presence of secondary Sjogren's syndrome are of less prognostic significance. Similarly a monoclonal paraprotein may identify patients with primary Sjogren's syndrome who have a particular risk of later lymphoma whilst this risk does not appear to extend to patients with systemic lupus erythematosus. Patients with an overlap syndrome do not appear to be at greater risk than those with "pure disease". The association of other rheumatological disease and paraproteinaemia is briefly discussed. PMID- 1591383 TI - Therapeutic implications of antisense oligonucleotides. AB - Antisense oligonucleotides and their derivatives have been shown to be specific inhibitors of gene expression. They are considered a very promising new generation of drugs, potentially useful in most human diseases, including cancers and viral infections. The elegance of the antisense oligonucleotides lies in their ability to bind, via standard Watson-Crick base pairing, a complementary region within a target mRNA. Although easily synthesized, therapeutic applications have been restricted by a number of difficulties including: stability, pharmacokinetic behavior (both a cellular and at systemic level), and the high cost of industrial production. The object of this review is to briefly describe the major properties of antisense oligonucleotides, the modalities currently under investigation to circumvent the difficulties in their use, and the up-to-date experimental applications, including findings from our own laboratory. As very few oligonucleotides need to be synthesized in order to obtain an active compound, compared with an average of 10,000 new standard compounds, prospects are extremely exciting and worthy of maximum attention. PMID- 1591384 TI - Interleukins modulate glucocorticoid-induced thymocyte apoptosis. AB - Glucocorticoid hormones, calcium ionophores and anti-CD3 monoclonal antibodies induce apoptosis in mouse thymocytes. This type of cell death, which is characterized by an extensive DNA fragmentation into oligonucleosomal subunits, occurs in the intrathymic process of negative selection, and is involved in the deletion of autoreactive T-cells during thymic maturation. A number of cytokines are able to modulate apoptosis, and interleukins, including interleukin-1, interleukin-2, and interleukin-4, play a crucial role in thymic maturation and T cell development. We tested the effects of several cytokines on the glucocorticoid hormone-induced apoptosis of mouse thymocytes in vitro, and demonstrated that interleukin-1 alpha, interleukin-2, and interleukin-4 inhibit the apoptosis induced by dexamethasone, but that interleukin-3 and interleukin-6 exert no noteworthy effect. Dose-response experiments indicated that interleukin 4 is more potent than interleukin-1 alpha and interleukin-2 in inhibiting dexamethasone-induced apoptosis. Furthermore, interleukin-4 fully inhibited the DNA fragmentation induced by the protein kinase-C activator 12-O tetradecanoylphorbol-13-acetate, but was ineffective against apoptosis induced by the calcium ionophore A23187. These results suggest that interleukins regulate the thymic selection process by acting as modulators of the negative selection process. PMID- 1591385 TI - Detection of liver involvement in inflammatory bowel disease by abdominal ultrasound scan. AB - Fifty patients with ulcerative colitis, 24 with Crohn's disease, and 50 controls were studied by liver function tests and abdominal ultrasound scan. Twenty-two percent of ulcerative colitis patients, 29% of Crohn's disease patients, and none of the controls showed abnormal liver function tests. All subjects with abnormal liver function tests also had changes in ultrasound liver scan, consisting of hepatomegaly and/or a dysechoic liver echo pattern. Furthermore, the same ultrasound changes were observed, in the absence of any liver function test abnormalities, in 58% of ulcerative colitis patients, 50% of Crohn's disease patients and 6% of controls (P less than 0.0005, inflammatory bowel disease versus controls). Overall, some evidence of liver involvement, as judged by abnormal liver tests and/or abnormal ultrasound liver scan, was detected in about 80% of inflammatory bowel disease patients. Six patients with minor abnormalities of liver function tests underwent liver biopsy and 5 of them had pericholangitis. Ultrasound liver scan may provide a useful tool to evaluate the occurrence of liver involvement in inflammatory bowel disease patients. PMID- 1591386 TI - Serum A1 and B apolipoprotein determination: comparison of an immunoturbidimetric method with a monoclonal-antibody-based radial immunodiffusion assay. AB - Epidemiological and clinical evidence have indicated that apolipoprotein A1 and B determination can better define the lipoprotein pattern in normal subjects and in subjects with coronary heart disease. In this paper, a recent immunoturbidimetric method for routine apolipoprotein A1 and B measurement (using the Turbitimer system and commercially available antisera) has been evaluated. The precision and the accuracy of the method have been previously considered. Within-run and between-run coefficients of variation (ranging from 1.67% to 5.04%) for both assays indicate good precision of the method. Accuracy was evaluated on 2 consecutive days (n = 10 each run) using a standard serum for apolipoprotein A1 and B. The bias obtained was 3.79% for apolipoprotein A1 and 2.30% for B. Apolipoproteins A1 and B were then measured in 100 normal and hyperlipemic sera with the immunoturbidimetric assay and radial immunodiffusion (using the monoclonal antibodies). The data obtained were evaluated by linear regression analysis (Al, r = 0.893; B, r = 0.862). The good correlation between the two methods suggests that the immunoturbidimetric assay can be usefully performed for routine apolipoprotein A1 and B determination because of its lower cost, rapidity, and simplicity. PMID- 1591387 TI - Volume, conductivity, and scatter changes of activated polymorphonuclear leukocytes: an estimation by Coulter Counter STKS analyzer. AB - Suspensions of phorbol myristate acetate-activated polymorphonuclear leukocytes were analyzed with a Coulter Counter STKS hematological analyzer. Phorbol myristate acetate activation induced an increase in polymorphonuclear leukocyte volume and conductivity, while scatter was unchanged. Phorbol myristate acetate activated neutrophils in a suspension containing nitroblue tetrazolium showed increased scatter. The rise in scatter was phorbol myristate acetate dose dependent, completely inhibited by diphenylene iodonium and partially by dimethyl sulfoxide, two inhibitors of NADPH oxidase. Zymosan-activated polymorphonuclear leukocytes were notably larger with a characteristic position on discriminant function 1 display (volume versus scatter) of the analyzer. Volume and conductivity changes were seemingly inexplicable features of phorbol myristate acetate activation. The rise in scatter was produced by cytoplasmic precipitation of reduced nitroblue tetrazolium and thus by O2-generation in phorbol myristate acetate-activated neutrophils. Zymosan phagocytosis was responsible for the notable rise in polymorphonuclear leukocyte volume. The analysis of activated polymorphonuclear leukocytes by Coulter Counter STKS may provide useful information on their activation and a pragmatic approach for studying function. PMID- 1591388 TI - [Resorts and public health]. PMID- 1591389 TI - [A study of mortality among male physicians in Chiba prefecture]. AB - In order to assess mortality patterns of Japanese physicians, the mortality during a 12 year period (July 1978-June 1990) among male members of the Chiba Medical Association was studied. The overall mortality among physicians was significantly lower than the general male population in Chiba prefecture (standardized mortality ratio [SMR] = 0.69). Physicians were found to have lower cause-specific mortality from cancer (SMR = 0.71), cerebrovascular disease (SMR = 0.42), pneumonia and bronchitis (SMR = 0.63), accidents (SMR = 0.37), and suicide (SMR = 0.29) than the general population, but to have higher mortality from senility (SMR = 1.75). When compared to the total working population and the professional and technical workers, all-cause mortality for physicians did not differ. Mortality from ischemic heart disease was significantly higher during 1979-1983, but was similar during 1984-1988. Analysis by specialty showed that during 1979-1983 internal medicine physicians had a lower mortality than surgeons, but this reversed during 1984-1988 with the former having a higher mortality than the latter. Over the whole period, no difference in mortality existed between internists and surgeons. A cohort of 2,502 male members that is being followed, showed that the mortality of physicians was lower than the general population. However, no significant difference between the internists and surgeons was observed in both overall and major cause-specific mortality. PMID- 1591390 TI - [Health effects and personal protection in pest control workers using organophosphorus insecticides]. AB - One hundred and sixteen pest control workers (16 termite control workers (Sprayer I), 46 cockroach or fly-control workers (Sprayer II) and 56 both termite and cockroach or fly-control workers (Sprayer III)) were surveyed by a questionnaire and health examinations. Variety and quantity of pesticide used, personal usage of protective devices (respirator, gloves, work clothes, under wear), and conditions related to bathing were studied by a questionnaire. Relationships between protective devices and blood cholinesterase activity (ChE) were also analyzed. Significant findings were as follows: Most of the pest control operators wore gum gloves and gas masks when involved in termite control. However in the case of cockroach or fly-control, 38% did not wear gloves, and for respiratory protection 44% wore gas masks while 25% of them did not even use any form of respirators. In spite of having better protective practices than sprayers II and III, sprayer I showed significantly lower plasma ChE activity than both sprayer II and III. Plasma ChE activity in sprayers who put on simple respirators tended to be lower than those using gas masks. Plasma ChE activity was also significantly lower in those workers who had less frequent changes of work clothes compared to those with more frequent. PMID- 1591391 TI - [Mass screening for detection of infants with hearing impairment. II. Screening items and risk factors of hearing impairment]. AB - Validity of the items included in a questionnaire for mass screening for hearing impairment of infants and the risk factors for hearing impairment of 4-month-old infants were studied. Qualitative differences in the questionnaire items were found that would be related to decisions regarding need for thorough examination or followup of a case. The combined use of the risk factors and the questionnaire for 4-month-old infants may considerably reduce the number of false positive cases. A case whose number of negative items was three or less and who had at least one risk factor at 4 months of age was shown to have a high risk of auditory impairment. The cut-off point for the followup screening questionnaires at 7- and 10-month old infants was determined to be at three or less and four or more items. PMID- 1591392 TI - [Rapid detection of motile Salmonella in chicken meat by the 1-2 Test]. AB - The 1-2 Test (BioControl) is an enrichment culture/immuno-diffusion assay for detecting Salmonella in foods by use of poly-H-antibodies. The performance of the 1-2 Test was compared with that of the traditional culture method on 85 chicken meat samples. The results were as follows: The detection frequency of Salmonella by the 1-2 Test 24-hour assay (28/85, 32.9%) was greater than that by the 8-hour assay (16/85, 18.8%) and almost equal to that by the traditional method (26/85, 30.6%). The 8-hour assay gave a 46.2% sensitivity and 93.2% specificity. The 24 hour assay gave an 84.6% sensitivity and 89.8% specificity. Detection appeared to show some influence from the number of Salmonella, number of viable cells (SPC) and coliform groups. Differences in serotypes of Salmonella detected by the 1-2 Test and the traditional methods were also observed. Although there were some differing results between the 1-2 Test and the traditional method, this system appears to be useful for detecting Salmonella in foods, since results can be obtained at least 24 hours earlier than by the conventional procedures. PMID- 1591393 TI - [An inquiry into the effects of working time and commuting time on lifestyle in white-collar workers]. PMID- 1591394 TI - [Geographical distribution of mortality and morbidity from stomach cancer in Saga prefecture]. PMID- 1591395 TI - [Role of staffs in "rehabilitation" by the Health and Medical Services Law for the Aged]. PMID- 1591396 TI - Ionspray mass spectrometry of marine toxins. III. Analysis of paralytic shellfish poisoning toxins by flow-injection analysis, liquid chromatography/mass spectrometry and capillary electrophoresis/mass spectrometry. AB - Ionspray mass spectrometry has been used to monitor the purification of saxitoxin, the parent compound in the family of toxins responsible for paralytic shellfish poisoning (PSP), from a strain of the dinoflagellate Alexandrium excavatum. Quantitative results obtained by flow-injection analysis are compared to those obtained by high-performance liquid chromatography with post-column oxidation and fluorescence detection. The coupling of liquid chromatography and capillary electrophoresis with ionspray mass spectrometry is described for the separation of mixtures of PSP toxins and the highly potent pufferfish toxin tetrodotoxin. Tandem mass spectrometry is used to provide the structural information, and the ability to distinguish isomeric PSP toxins both chromatographically and mass spectrometrically is demonstrated. PMID- 1591397 TI - Desorption of ions from locust tissues. II. Metabolites of E-destruxin using negative-ion fast-atom bombardment mass spectrometry. PMID- 1591398 TI - The correct molecular weight of myoglobin, a common calibrant for mass spectrometry. AB - Myoglobins from horse heart muscle, horse skeletal muscle and sperm whale are widely used as calibration standards or test compounds for various mass spectrometric methodologies. In all such cases reported in the literature, a molecular weight value is used (16,950.5 and 17,199, respectively) which is based on the assumption that amino acid 122 in this 153 amino-acid-long protein is asparagine, overlooking a published suggestion that it is aspartic acid instead. Since the mass assignment accuracy for matrix-assisted laser desorption mass spectrometry is reported to be +/- 0.01% and for electrospray ionization +/- 0.0025%, and error of one mass unit in approximately 17,000 would be significant. The mass-to-charge ratio of ions of the tryptic peptide encompassing amino acid 122 derived from commercially available horse heart and horse skeletal myoglobins, the apomyoglobin of the latter, and the tryptic and chymotryptic peptide of sperm whale myoglobin proved that in both proteins amino acid 122 is indeed aspartic acid, rather than asparagine. This finding was further confirmed by the collision-induced dissociation spectra of the [M + H]+ ions of the tryptic peptides from the horse myoglobins and the chymotriptic peptide from sperm whale myoglobin. Thus, the correct molecular weight of horse myoglobin is 16,951.49 and that of the sperm whale protein is 17,199.91. PMID- 1591399 TI - Electrospray ionization mass spectra of hemoglobin and transferrin by a magnetic sector mass spectrometer. Comparison with theoretical isotopic distributions. AB - Electrospray ionization mass spectra of human hemoglobin chains and of transferrin were acquired on a magnetic sector mass spectrometer. The observed molecular ion for each hemoglobin chain was in good agreement with the theoretical isotopic distribution at a reasonable resolution of 2000. The clear separation of a variant beta-chain in admixture with the normal counterpart at mass 15,867 that differed from it by 14 Da (0.09%) ensured that a smaller mass difference could be detected. The molecular ions for human transferrin were too broad compared with the theoretical shape to determine the molecular mass accurately, probably due to the heterogeneity of the carbohydrate moiety. A decrease in mass by neuraminidase digestion, however, determined the average number of sialic acids in the molecule. PMID- 1591400 TI - Negative-ion mass spectra of methylated diuretics. AB - The negative-ion mass spectra of 19 methylated diuretics are presented and correlations between these spectra and the chemical structures of the compounds are indicated. The spectra are of interest as the basis of an analytical method for the identification of small quantities of diuretics in the urine of hypokalemic patients. PMID- 1591401 TI - A protocol for rapid screening of proteoglycan-degrading metalloproteinase inhibitors. AB - A procedure is described for rapid, high-volume screening of proteoglycan degrading metalloproteinase inhibitors. The procedure was developed by modifying the proteoglycan-polyacrylamide particle assay for proteases, polysaccharidases (Nagase and Woessner, 1980), and the 1,9-dimethylmethylene blue (DMB) assay for sulfated glycosaminoglycans (Farndale et al., 1982). The following modifications have made the new protocol suitable for evaluating a large number of compounds simultaneously: 1) Pipetting steps were automated using a pipetting robot. 2) Speed and sensitivity of the 1,9-dimethylmethylene assay were increased by scaling down the assay and measuring absorbance using an automatic multiwell plate reader. 3) Data capture and analysis were simplified using computer programs. The modified procedure is rapid, sensitive, reliable, and requires a small sample size. Above all, the procedure is suitable for high-volume screening: approximately 100 compounds can be evaluated in 1 day. PMID- 1591402 TI - Real-time ultrasonography as a noninvasive tool for the examination of canine gallbladder emptying: a validation study. AB - An ultrasonographic measurement of the gallbladder volume based on an ellipsoid approximation of the gallbladder shape was validated in vivo in the dog. The mean difference between the ultrasonographically determined and the true gallbladder volumes amounted to 2.0 +/- 1.6 cm3 (mean +/- SD), whereas the regression line computed for the ultrasonographically measured versus true gallbladder volumes was y = 0.892x + 3.0, r = 0.955, p much less than 0.001. The ultrasonographic method enabled a noninvasive, repetitive measurement of either a meal- or caerulein-induced gallbladder emptying in the dog. PMID- 1591403 TI - In situ perfusion in the rabbit: effects of different umbilical flow rates on placental transfer of compounds. AB - The effects of different umbilical flow rates on the placental transfer of compounds were studied in order to optimize an in situ placental perfusion model in the rabbit for establishing the most suitable perfusion flow rate range and assessing alterations in the placental architecture related to the umbilical flow. Placental transfer of a tool compound theophylline (TH) at different umbilical flow rates was compared with that of antipyrine (AP), the commonly used indicator of placental exchange, in maternal arterial drug steady-state conditions after a two-step infusion program. Placentas of six rabbits were perfused for 250 min with Earle's enriched bicarbonate buffer at 0.5, 1, 1.5, 2, 3, and 4 mL/min flow rates. Plasma and placental perfusate effluent biochemical parameters, gas exchange, body temperature, and electrocardiogram were recorded. Umbilical arterial perfusion pressure was controlled throughout the experiments. A detailed pharmacokinetic analysis of unbound maternal plasma, perfusate TH, and AP concentrations was made. Placental clearance of TH and AP rose up to the 3 mL/min flow rate and then remained constant. Placental clearance was linear up to 2.0 mL/min for TH and 1.5 mL/min for AP. The umbilical flow rate limit was 1.76 +/- 0.29 mL/min for TH and 1.72 +/- 0.49 mL/min for AP. The clearance index was 0.71 +/- 0.04. The correlation between umbilical flow and perfusion pressure was linear, with mean values from 4 to 25 mmHg. Placental resistances did not change significantly at all flow rates with mean values between 6 and 9 mmHg/mL/min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591404 TI - Rapid evaluation of the efficacy of pharmacologic agents and their analogs in enhancing bladder capacity and reducing the voiding frequency. AB - We report here the results of a simplified screening method to rapidly compare the pharmacologic action of drugs relevant to the urinary tract. This method avoids the use of anesthesia and of external infusion into the bladder relying on the physiological stimulation of the volume-evoked micturition reflex (VEMR) by diuresis. Mature female rats weighing 240-310 g were placed in restrainer cages that afforded access to food and water but limited movement. Under the rear of the rat, a collecting funnel and weight measuring device was secured. For each VEMR, the weight of the volume voided was recorded on a polygraph which also provided a record of the time of voiding. To evaluate the relative pharmacologic efficacy of the drug under study, 1 mg/kg furosemide along with the drug to be evaluated was diluted in 5 ml of saline and injected subcutaneously. Rats received approximately equimolar concentrations of thiphenamil and 15 other analogs, Ca2+ channel blockers, and K+ channel openers. The furosemide was given to obtain a controlled level of diuresis and avoid the effects of circadian variations in urine flow. Parameters considered were 1) mean volume voided per VEMR, 2) frequency, 3) output, and 4) latency. This model allows the rapid evaluation of drugs designed to increase bladder capacity and decrease the frequency of voiding, and it is particularly useful in evaluating the relative efficacy of drugs that are chemical analogs. PMID- 1591405 TI - Lipophilicity of opioids determined by a novel micromethod. AB - The lipophilicity of various mu-selective opioids was determined by measuring their distribution between n-octanol and Tris.HCl buffer, pH 7.4, by a procedure requiring submicromolar concentrations (submilligram amounts) of the compounds. After partitioning at 25 degrees C, the concentrations of opioids in the aqueous phase was quantified by their displacement of bound [3H]Tyr-Ala-Gly-(Me)Phe-Gly ol (DAMGO) from opioid receptor in brain membranes. The obtained distribution coefficients (log Papp) agreed well with respective values determined previously with other, less sensitive or more cumbersome, methods of quantitation. The procedure is precise and versatile, and offers the routine assessment of lipophilicity as part of the in vitro characterization of opioids frequently available in limited quantities. In principle, the method is applicable to any compound whose binding to its receptor is quantifiable. PMID- 1591406 TI - The isolated blood-perfused pig ear: an inexpensive and animal-saving model for skin penetration studies. AB - To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3 hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models. PMID- 1591407 TI - Liver microsomes contain multiple forms of inositol 1,4,5-trisphosphate binding proteins: identification by nitrocellulose blot overlay. AB - A group of proteins binding to inositol 1,4,5-trisphosphate (IP3) has been identified in rat liver microsomes by a nitrocellulose blot-overlay technique. Proteins were resolved by SDS-PAGE, blotted on nitrocellulose and incubated with [32P]IP3 followed by autoradiography. Approximately eight IP3-binding polypeptides ranging M(r) 23-50 kDA were present exclusively in microsomes; these were absent from plasma membrane and mitochondrial fractions. Binding of [32P]IP3 to these proteins was displaceable to a great extent by 5 microM unlabeled IP3 but not by 10 microM IP1, IP2, IP4, ATP, or GTP gamma S. These results suggest that liver microsomes contain multiple forms of IP3-binding proteins that can be detected by this new method. PMID- 1591408 TI - A sciatic nerve blockade method to differentiate drug-induced local anesthesia from neuromuscular blockade in mice. AB - This report introduces a simple and easy technique for animal handling and drug administration into the sciatic nerve area for determining local anesthesia and neuromuscular blocking activity in mice. The drugs were injected into the popliteal space of the right hindlimb (i.e., the sciatic nerve area). The loss of motor activity of the right hindlimb was taken as a sign of producing local anesthesia. A positive local anesthetic activity was recorded when a mouse was only able to walk using three limbs on an inverted wire mesh screen and the injected limb was hanging in the air. This method is superior to the commonly used techniques of applying drugs to the rabbit's cornea, the guinea pig's back skin, or the root of the mouse tail to determine the reduced reflex responses and to assess the local anesthetic activity. The present method has evaluated a number of drugs (cocaine, lidocaine, procaine, propranolol, quinidine, quinacrine, verapamil, and diltiazem), which are known to produce local anesthesia. The sciatic nerve blockade technique is also capable of determining neuromuscular blocking activity of drugs, in which the end point of activity taken is different from that for local anesthetic drugs. The method reported here has been validated by reference neuromuscular blocking agents (d-tubocurarine, decamethonium, and succinylcholine). A positive neuromuscular blockade was recorded when a mouse was unable to stay on the inverted wire mesh screen. The information provides not only the local anesthetic or neuromuscular blocking potency of drugs but also duration of action of drugs. PMID- 1591409 TI - Flat embedding and immunolabelling of SW 1116 colon carcinoma cells in LR white: an improved technique in light and electron microscopy. AB - Human SW 1116 colon carcinoma cells were grown on matrix-covered coverslips and flat embedded in specially prepared gelatin capsules in the hydrophylic resin LR White. Dehydration and polymerization were carried out so as to maximize preservation of antigenicity. Sections were cut perpendicular to the substratum. To visualize mucin, semithin sections of SW 1116 cells were stained with periodic acid Schiff (PAS) reagent for light microscopy, and ultrathin sections were labelled with a monoclonal mucin antibody (Mab 19-9) and immunogold for electron microscopy. Immunofluorescence was carried out on whole cultured cells using Mab 19-9. The morphological preservation of SW 1116 cells embedded in LR White was comparable to that of Epon-embedded cells. Mucin was localized on the microvillar surface of the apical plasma membrane and occasionally in intercellular spaces between adjacent cells. Mucin was also present in vesicles in the apical and lateral part, and to a lesser extent in the basal part of the cells. We conclude that this new technology significantly improves the morphological preservation of cells and tissues in LR White, while also serving to sustain the antigenicity of cellular antigens. PMID- 1591410 TI - Stepped surfaces of sapphire (alpha-Al2O3) with low Miller indices. AB - Oxygen-annealed surfaces of sapphire with low Miller indices ((0001), [1010], [1120], [1011]) have been studied in both transmission electron microscopy (TEM) and reflection electron microscopy (REM) configurations. The significance of REM diffraction conditions for the determination of the nature of the step heights is discussed. The relationship between the TEM and REM images is explained. The structural features are those that might be expected from considerations of the atom arrangement in the low Miller index planes. The structural features on the surfaces varied with respect to annealing temperature and surface condition. Thermally stable structures that might appear from consideration of the equilibrium-annealing temperature are proposed. PMID- 1591411 TI - Localization of adenovirus DNA by in situ hybridization electron microscopy. AB - Biotinylated deoxyadenosine triphosphate (dATP) (Bio-7-dATP) and 3H deoxythymidine triphosphate (dTTP) labeled adenovirus DNA were hybridized in situ to thin sections of Lowicryl K4M-embedded and whole-mount extracted HeLa cells infected with adenovirus. The biotinylated probe was detected by exposing the extracted cells or sections to antibodies against biotin followed by colloidal gold-conjugated secondary antibodies and then critical-point dried while 3H-dTTP labeled probe by electron microscopic autoradiography. On Lowicryl K4M sections, gold particles and silver grains were mainly restricted in the nucleus. Furthermore, whole-mount results suggested that replicating adenovirus DNA is localized on the nuclear matrix of its host cell. In this paper, the described non-radioactive procedures for hybrid detection offered several advantages: a) rapid signal detection; b) superior morphological preservation and spatial resolution; c) precise localization; and d) on Lowicryl K4M sections, signal to noise equivalent to radiolabeling. PMID- 1591412 TI - Scanning electron microscopy of negatively stained catalase on a silicon wafer. AB - A high-resolution scanning electron microscope capable of 7 A spatial resolution at 30-kV accelerating voltage was used to observe negatively stained protein molecules. Thin platelet crystals, densely packed monolayers, and low-density deposits of beef liver catalase were prepared on the surface of silicon wafers and negatively stained with phosphotungstic acid. The tetrameric structure of the catalase molecule was observed for the first time by scanning electron microscopy on the surface of the smooth silicon wafer. PMID- 1591414 TI - Unified approach for computing interplanar spacing and location of projection of HOLZ reflection onto the ZOLZ. PMID- 1591413 TI - Acetonitrile as a substitute for ethanol/propylene oxide in tissue processing for transmission electron microscopy: comparison of fine structure and lipid solubility in mouse liver, kidney, and intestine. AB - Tissue processing for transmission electron microscopy (TEM) is commonly accomplished using ethanol (EtOH) as a dehydrating solvent and propylene oxide (PO) as a transition fluid. Both solvents have some undesirable properties: EtOH solubilizes lipids; PO is highly flammable, volatile, toxic, and potentially carcinogenic. Their replacement by a compound devoid of these characteristics is therefore desirable. Acetonitrile (AN) appears to be such a solvent. It is freely miscible with water, alcohols, acetone, and epoxy resins; it does not interfere with epoxy polymerization; and the resulting cured resins have excellent cutting quality and beam stability. AN is also an excellent dehydrating agent whose use does not necessitate modification of current techniques. Most importantly, the low solubility of phospholipids (PL) in AN limits the loss of membrane lipids and, hence, leads to a better preservation of tissue features. PMID- 1591415 TI - Observation by transmission electron microscopy of etch figures obtained on an organic molecular crystal. AB - It is interesting to apply the method of etch figures to the study of organic molecular crystal defects, by observing the etch pits as soon as they are produced. We have set up a method to determine the geometrical forms of such small etch pits, observed on pre-shadowed replicas of naphthalene crystal surfaces. The described experimental procedure was designed to avoid artefacts due to vacuum sublimation and moisture traces on the replicated surface. Stereoscopic observation makes interpretation possible. The 3-D morphology and size of etch figures smaller than 1 micron can be determined. PMID- 1591416 TI - Ultrathin sectioning of different areas of the same semithin section. PMID- 1591417 TI - Orientation of human spermatozoa for electron microscopy: a fast, simple method. PMID- 1591418 TI - Assessment of the pharmacy service needs of HIV-positive outpatients receiving zidovudine. AB - OBJECTIVE: To determine the pharmacy service needs of HIV-positive outpatients. DESIGN: Anonymous mail-in survey. SETTING: Accredited, not-for-profit, outpatient pharmacy. PATIENTS: A total of 226 men receiving refill prescriptions for zidovudine. Relevant demographics: for 91 percent, homosexual behavior was the primary HIV risk factor; 75 percent were HIV positive with low CD4+ count; 68 percent had been receiving zidovudine for less than 12 months. MEASUREMENTS: Survey questions determined patients' past experience and satisfaction with pharmacy services, description of pharmacy service needs, drug history, and sociodemographics. MAIN RESULTS: Confidentiality was desired by 90 percent of patients. Patients also expected to receive private medication counseling on zidovudine routinely and to receive other information upon request. Twenty patients expected no medication counseling. Such patients were more likely to have contracted HIV by transfusion or intravenous drug abuse (p less than 0.05). CONCLUSIONS: The perceived pharmacy service needs of outpatients taking zidovudine can reasonably be met in all ambulatory settings. Pharmacists must be aware that all patients do not have the same needs and should tailor their activities to the needs expressed by individual patients. PMID- 1591419 TI - Predictive performance of equations to estimate creatinine clearance in hospitalized elderly patients. AB - OBJECTIVE: To ascertain the clinical accuracy of equations that estimate creatinine clearance to predict the correct drug doses in hospitalized elderly patients DESIGN: Single 24-hour creatinine clearance measurement compared with estimated creatinine clearances derived from eight equations using total and modified ideal body weight SETTING: Nonintensive care medical and surgical units at a county hospital PATIENTS: 15 patients with urethral catheters were enrolled in each of three age groups: 65-75, 76-85, and greater than or equal to 86 years MAIN OUTCOME MEASUREMENTS: Drug-dose predictions, bias, precision, and absolute errors RESULTS: The bias for all equations was -4.0-42.0 mL/min (-0.07-0.70 mL/s) and the precision was 10.8-47.4 mL/min (0.18-0.88 mL/s). The Jelliffe 1973, Hull et al., and Mawer et al. equations were the least biased and the Jelliffe 1973 was the most precise, followed by the Mawer et al., Hull et al., and Cockcroft Gault equations. The percent of patients with absolute percent errors greater than 20 percent were 38 percent for Jelliffe 1973, 36 percent for Mawer et al., 40 percent for Hull et al., and greater than 50 percent for the other equations. The percent of patients receiving correct drug doses was 67 percent for Jelliffe 1973, 58 percent for Gates, 51 percent for Mawer et al. and Hull et al., and less than 50 percent for the other equations. Within various age, renal function, serum creatinine, and albumin subgroups, the Jelliffe 1973 estimates were least biased and most precise, followed by the Cockcroft-Gault estimates. Generally, estimates using modified lean body weight performed better than did those using total body weight. CONCLUSIONS: The Jelliffe 1973 equation with modified lean body weight was the best equation, followed by the Cockcroft-Gault equation. Even with the best equation, 33 percent of the patients would have received an incorrect drug dose. Therefore, some elderly patients may still require a measured creatinine clearance. PMID- 1591420 TI - Fulminant hepatic failure possibly related to ciprofloxacin. AB - OBJECTIVE: To report a case of hepatic failure in a patient who was receiving oral ciprofloxacin. DATA SOURCES: Case reports, review articles, and relevant laboratory studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: A 66-year-old man was admitted for hip arthroplasty and developed fulminant hepatic failure during oral ciprofloxacin therapy. Ciprofloxacin was started on postoperative day 13 for treatment of a urinary tract infection. Over the next three days he became confused and hypoglycemic. His prothrombin time increased to greater than 90 s. Serum aspartate aminotransferase and alanine aminotransferase concentrations were markedly elevated. The patient died on postoperative day 20. Postmortem examination of the liver revealed extensive centrilobular necrosis. A skin biopsy was consistent with a drug reaction. It is unknown whether the patient had received a quinolone compound in the past or had a history of exposure to hepatotoxins. CONCLUSIONS: It cannot be concluded that ciprofloxacin directly caused hepatic failure in this patient. It is possible that the drug evoked a hypersensitivity reaction or exacerbated a preexisting hepatotoxicity. A detailed patient history and evaluation of hepatic function should be obtained prior to initiating ciprofloxacin therapy. A nonquinolone antimicrobial may be a safer alternative for patients with hepatic dysfunction. PMID- 1591421 TI - Successful use of higher-than-recommended dosage of imipenem in Pseudomonas aeruginosa endocarditis. AB - OBJECTIVE: To report a case of Pseudomonas aeruginosa endocarditis that was successfully treated with high-dose imipenem/cilastatin and to discuss dosage modification based on individual pharmacokinetic parameters. DATA SOURCES: Clinical studies, review articles, and relevant laboratory and pharmacokinetic information. CASE SUMMARY: A 27-year-old man with right-sided P. aeruginosa endocarditis was successfully treated with long-term imipenem/cilastatin and tobramycin. The imipenem dose required to achieve therapeutic serum concentrations and cidal activity was 6 g/d. The manufacturer's recommended maximum dose is 4.0 g/d or 50 mg/kg/d. Because of the patient's large apparent volume of distribution, low serum imipenem concentrations, and lack of serum cidal activity, the clinical decision was made to increase the dose to 6 g/d or 54 mg/kg/d. Treatment was tolerated for seven weeks without any adverse effects. The patient remains free of symptoms 24 months after the diagnosis. CONCLUSIONS: Careful and discriminate use of larger-than-recommended doses of imipenem may be indicated in certain clinical situations. Dosage may need to be adjusted to body size in order to obtain optimal serum concentrations and activity. PMID- 1591422 TI - Danazol increases the anticoagulant effect of warfarin. AB - OBJECTIVE: To report two cases demonstrating an interaction between danazol and warfarin, resulting in the potentiation of warfarin's effect and bleeding complications. DATA SOURCES: Case reports, review articles, and studies identified by MEDLINE. STUDY SELECTION: All published English-language reports involving danazol and warfarin interactions were reviewed. DATA SYNTHESIS: Danazol, a synthetic testosterone derivative, is used in the treatment of endometriosis, fibrocystic breast disease, menorrhagia protein C deficiency, and hemophilia. We describe two cases including an interaction between danazol and warfarin, resulting in bleeding complications. There are at least two other reported cases of this interaction. This interaction may be attributable to several mechanisms. Danazol may inhibit the metabolism of warfarin and/or it may have a direct effect on the coagulation and fibrinolytic systems. CONCLUSIONS: Based on this report and other published cases, clinicians must be aware that danazol may increase the anticoagulant effect of warfarin. Patients receiving warfarin who are prescribed danazol must be monitored closely to prevent excessive anticoagulation and subsequent bleeding. Studies are needed to determine the frequency of this interaction and its underlying mechanisms. PMID- 1591423 TI - A nationwide investigation of a possible protamine drug-product defect. AB - OBJECTIVE: To follow-up a report submitted to FDA Spontaneous Reporting System, we investigated the hypothesis that there was not a striking increase in unexpected deaths within four hours after elective coronary artery bypass surgery associated with protamine sulfate use. DESIGN: Surveys were mailed to clinical pharmacists at 521 hospitals participating in the Drug Surveillance Network. Questionnaires were to be completed with the assistance of cardiac surgeons and anesthesiologists. Hospitals responding with a suspected problem with protamine were contacted via telephone. RESULTS: Surveys were received from clinical pharmacists at 380 hospitals (73 percent response rate) and 29 hospitals reported the occurrence of potential problems associated with protamine during coronary artery bypass graft surgery. Telephone interviews of the positive responders yielded six cases of possible myocardial decomposition potentially associated with protamine. There was no association with a specific distributor, however, and none of the hospitals reported a dramatic increase in serious adverse events around the time of index cases. CONCLUSIONS: There was no evidence of a widespread public health problem with protamine and a product recall was not necessary. The high response rate and the ability to follow-up with telephone interviews suggests that the Drug Surveillance Network is an effective mechanism for investigating possible outbreaks of serious adverse events in the hospital setting. PMID- 1591424 TI - Clindamycin in the treatment of toxoplasmosis in AIDS. PMID- 1591425 TI - Gammahydroxybutyrate in narcolepsy. PMID- 1591426 TI - Controversies over the use of magnesium sulfate in delirium tremens. AB - OBJECTIVE: To critically address the controversy of using parenteral magnesium sulfate in delirium tremens (DT). DATA SOURCES: English-language journal articles published between 1954 and 1987. STUDY SELECTION: All literature available, mostly case reports, that either support or discourage magnesium sulfate administration to patients with DT. DATA EXTRACTION: Pertinent information (as judged by the authors) was summarized and interpreted. DATA SYNTHESIS: DT has long been associated with magnesium deficiency because many alcoholic patients with DT have low serum magnesium concentrations. Recent literature, however, suggests that hypomagnesemia is not noted universally in this patient population and that patients' serum magnesium concentrations may return to normal without exogenous magnesium administration. Thus, there is most likely not a specific causal relationship of hypomagnesemia in DT. CONCLUSIONS: Routine administration of parenteral magnesium sulfate in patients with DT is not recommended. PMID- 1591427 TI - The efficacy of ergogenic agents in athletic competition. Part II: Other performance-enhancing agents. AB - OBJECTIVE: To summarize the literature describing the epidemiology, pharmacology, efficacy, and adverse effects associated with growth hormone (GH), caffeine, aerobic metabolism facilitator (AMF), and sympathomimetic use among athletes. DATA SOURCES: Relevant articles were identified from a MEDLINE search using the search terms "Doping in Sports," "Blood," "Caffeine," "Cocaine," "Erythropoietin," "Somatotropin," and "Sympathomimetics (exploded)." Additional references were found in bibliographies of these articles. STUDY SELECTION/DATA EXTRACTION: We reviewed studies of ergogenic drug (ED) use among athletes. Interpretation of these studies is difficult because of poor research design and the paucity of information available. This necessitated the inclusion of many anecdotal or conjectural reports in our review. DATA SYNTHESIS: There are no studies documenting an ergogenic effect associated with GH use in humans or animals. It is still unknown whether GH abuse causes adverse effects in healthy adults, although GH-induced acromegaly has been suspected. Amphetamines, cocaine, and caffeine are thought to improve performance via enhanced concentration among athletes. Amphetamines and cocaine may increase aggressiveness. The ergogenic effects of other sympathomimetics including ephedrine and phenylpropanolamine are unclear. AMFs (e.g., blood doping, epoetin) enhance aerobic metabolism and endurance by increasing the oxygen-carrying capacity of the blood. Risks associated with excessive AMF use include increased blood viscosity and clotting. CONCLUSIONS: Athletes view EDs as an essential component for success. Without adequate intervention measures, ED abuse is likely to continue unchecked. PMID- 1591428 TI - Guidelines for continuous infusion medications in the neonatal intensive care unit. AB - OBJECTIVE: To present practical guidelines in tabular form for dosage, calculation, preparation, and monitoring of common medications administered by continuous infusion to neonatal intensive care patients. DATA SOURCES: Review articles and clinical trials were identified through a computer literature search with subsequent bibliography scanning. STUDY SELECTION: Articles selected for review were considered important contributions. DATA EXTRACTION: Data from human studies and review articles published in the English language were evaluated. DATA SYNTHESIS: In emergency situations, physicians and other healthcare providers caring for critically ill newborns often perform rapid calculations to determine the dosage and rate of continuous intravenous medication infusions. Because of the crisis situation, there is the potential for calculation errors. We compiled a concise table designed to provide a standardized method for the administration of emergency medications to neonatal intensive care patients. This table must be used in conjunction with clinical judgment and each medication infusion rate must be adjusted to the patient's clinical response and individual parameters. CONCLUSIONS: These guidelines help to minimize the volume of fluid needed for medication administration and facilitate the calculation, preparation, and timely administration of these medications, thus preventing errors that might occur in an emergency situation. PMID- 1591429 TI - Automated therapeutic drug monitoring in an ambulatory care endocrine clinic. AB - OBJECTIVE: To develop and implement an automated therapeutic drug monitoring system for accessing data from endocrine clinic patients who had been prescribed insulin, oral hypoglycemic agents (OHA), or levothyroxine. DATA SOURCES: We designed a computer system to retrieve clinical data from the Medical Information System (MIS), a centralized hospital computer system, and import this information directly into a Macintosh personal computer. Physician entry of prescriptions for insulin, OHA, or levothyroxine into MIS formed the basis for a computer program to retrieve daily diagnostic and prescription information, demographics, and laboratory analyses, including blood glucose and glycosylated hemoglobin for insulin and OHA orders and free and total thyroxine, total triiodothyronine, and thyroid stimulating hormone for levothyroxine orders. The information was imported into a database program (4th Dimension). RESULTS: The system identifies laboratory values outside of predetermined therapeutic ranges, maintains an up-to date patient profile, and edits and generates reports. Preliminary experience suggests that automation eliminates 75-90 percent of the time required to manually collect the same information, and improves the accuracy, comprehensiveness, and utility of reports. CONCLUSIONS: Automated therapeutic drug monitoring minimizes the time required to collect clinical data, alerts clinicians to potential problems, and provides a means to assess overall therapeutic management. Our methodology can be used to evaluate other medications in a variety of general or specialty clinics. PMID- 1591431 TI - Pharmacy computer prescription databases: methodologic issues of access and confidentiality. AB - OBJECTIVE: To examine methodologic issues of access and confidentiality regarding the use of pharmacy computer prescription databases (PCPDs) for participant selection to receive mailed, self-administered, hypertensive quality-of-life survey outside a primary-care setting. DESIGN: Two separate PCPD searches by pharmacist owners for patients prescribed at least one of 130 potential antihypertensive medications. The first PCPD used a nonrandom sample of all patients (n = 635); the second PCPD used a random sample (n = 100) of three specific antihypertensive drug groups. Research protocol was approved by the investigators' institutional review board. SETTING: Two independent, privately owned PCPDs. PATIENTS OR OTHER PARTICIPANTS: Individuals prescribed at least 1 of 130 PCPD medications potentially used in antihypertensive treatment. INTERVENTIONS: Individually addressed cover letter on pharmacy letterhead signed by a pharmacist requesting voluntary completion of the enclosed, self administered, opinion survey on quality of life. MAIN OUTCOME MEASURE: Anonymous survey return to off-site post office box in envelope provided. RESULTS: Favorable or no opposition to PCPD methodology from pharmacist or participants. Ethical opposition was encountered when incorporating PCPD sampling technique into grant proposal. CONCLUSIONS: The American Pharmaceutical Association Code of Ethics is used as a basis to provide recommendations to examine and justify PCPD investigative use. Increasing availability of PCPD technology encourages more efficient and easier methods of research strategy. PCPD use, however, demands identical stringent guidelines used in traditional research and raises potential issues regarding pharmacist-patient confidentiality as well as the right of PCPD use by others. PMID- 1591430 TI - Drug-use patterns among black and nonblack community-dwelling elderly. AB - OBJECTIVE: To describe and compare drug-use patterns among black and nonblack community-dwelling elderly. DESIGN: Survey. SETTING: Five-county urban and rural region in Piedmont, NC. PARTICIPANTS: Stratified probability household sample of 4164 community residents aged 65 or older from the Piedmont Health Survey of the Elderly (65 percent women, 54 percent black, mean age 73.56 +/- 6.74 y). MAIN OUTCOME MEASURES: Prevalence of medication use and mean drug use; therapeutic medication category use. RESULTS: Data were weighted to represent the population in this geographic area. Fewer blacks reported the use of over-the-counter (OTC) medications and total medications than did nonblacks (66 vs. 76 percent and 88 vs. 92 percent, respectively; p less than 0.001). Compared with nonblacks, blacks reported using a lower mean number of prescription (2.02 vs. 2.35; p less than 0.001), OTC (1.12 vs. 1.42; p less than 0.001), and total (3.14 vs. 3.77; p less than 0.001) drugs. The therapeutic medication categories varied by race for prescription cardiovascular, analgesic, and central nervous system (CNS) drugs and OTC nutritional supplements. More nonblacks than blacks reported the use of analgesics (62.5 vs. 55.6 percent, respectively; p less than 0.001), CNS drugs (26.1 vs. 14.2 percent, respectively; p less than 0.001), nutritional supplements (27.5 vs. 16.9 percent, respectively; p less than 0.001), and gastrointestinal agents (29.0 vs. 23.5 percent, respectively; p less than 0.001). Blacks were more likely to report problems in managing their medications than were nonblacks (9.0 vs. 6.1 percent, respectively; p = 0.001). CONCLUSIONS: Our data suggest that there are distinct racial differences in medication-use patterns among the elderly. PMID- 1591432 TI - The effect of physician education on knowledge of drug therapeutics and costs. AB - OBJECTIVE: To determine if a clinical pharmacist-sponsored education program regarding physician knowledge of drug costs and therapeutics would change drug utilization and costs for specific high-cost groups of drugs in a pediatric critical care unit (PCCU). STUDY DESIGN: Prescribers within the PCCU completed a questionnaire addressing drug costs and therapeutic issues. Subsequent to the questionnaire the PCCU liaison pharmacist implemented a visual display of monthly drug costs, an education program that included the presentation of questionnaire results, and drug information lectures discussing controversial therapeutic issues. After the education program participants again completed the questionnaire. SETTING/PARTICIPANTS: The study was conducted in a 13-bed PCCU in a regional children's hospital. The participants were postgraduate trainees in pediatrics and critical care medicine as well as attending staff in the PCCU. OUTCOME MEASURES: The main outcome measure was the score on a test addressing drug costs and therapeutic issues. RESULTS: The mean overall posteducation score (52.5 percent) improved significantly from the preeducation score (46.4 percent). The preeducation questionnaire results indicated increased knowledge of costs by residents and increased knowledge of therapeutics by attending physicians. The number of educational sessions attended appeared to be associated with improvement in overall questionnaire scores. CONCLUSIONS: There was improvement in knowledge of drug costs and therapeutics associated with the educational program. Although this relationship did not reach statistical significance, this may be related to the relatively small sample size of our study. Our results suggest that clinical pharmacists can positively influence physicians' knowledge on drug costs and therapeutics. PMID- 1591433 TI - Pharmaceutical care for patients with HIV infection. PMID- 1591434 TI - Introduction to the "HIV and AIDS" column. PMID- 1591435 TI - Ambulatory care pharmacy services: the incomplete agenda. AB - OBJECTIVE: To review studies that document the impact of clinical pharmacy services in ambulatory care settings and to propose standards of practice and resource allocation needs in ambulatory care. DATA SOURCES: English-language literature from 1970 through 1991 was reviewed and the representative literature is described. STUDY SELECTION: Studies were selected that examined the impact of clinical pharmacy services on patient outcomes and costs. Studies that evaluated pharmacist consultations by blind peer-review panels were also evaluated. DATA EXTRACTION: Trials were assessed based on their methodologies and ability to assess the value of clinical pharmacy services on patient outcomes. DATA SYNTHESIS: Numerous studies from the past 20 years are described illustrating the impact that ambulatory care pharmacy practitioners have made on patient care. These studies demonstrate that clinical pharmacists in ambulatory care not only serve as consultants on pharmacotherapy issues, but also can improve the quality of care for individual patients. CONCLUSIONS: Based on the studies cited and the needs of ambulatory patients, this article highlights the authors' views on what the standards of practice should be for ambulatory care practitioners and where resources should be allocated as ambulatory programs are expanded. PMID- 1591436 TI - Drug interactions: Part I. PMID- 1591437 TI - Acute renal failure associated with the use of over-the-counter ibuprofen. PMID- 1591438 TI - Two episodes of carbamazepine-induced severe thrombocytopenia in the same child. PMID- 1591439 TI - Comment: bacterial endocarditis recommendations. PMID- 1591440 TI - Stress and social support as predictors of dietary compliance in hemodialysis patients. AB - This study examined the effects of minor stress on variations in biochemical indices of dietary compliance in hemodialysis patients. Subjects completed the Schedule of Recent Events, the Weekly Stress Inventory, and the Social Support Questionnaire. In addition, two biochemical measures of dietary compliance were obtained from the patients' medical charts. Multiple regression analysis, with baseline levels of compliance and the relatively stable influence of major life events and social support controlled for, revealed that minor stress was significantly predictive of changes in dietary compliance. The results suggest that minor stress may affect health status in the chronically ill by reducing compliance behaviors. PMID- 1591441 TI - Hostility: relationship to lifestyle behaviors and physical risk factors. AB - The relationship between hostility and coronary artery disease may be partially mediated by unhealthy lifestyle behaviors. This study examined the relationship between hostility, lifestyle behaviors, and physical risk factors in 138 adult men and women. Subjects completed the Cook and Medley Hostility Scale (Ho scale) and self-reports of their dietary habits, consumption of alcohol and cigarettes, and physical activity. Recent findings indicated that a composite hostility score from three rationally derived subscales of the Ho scale tapping the dimensions of cynicism, hostile affect, and aggressiveness was a better predictor of mortality than the total Ho score. Thus, this composite measure of hostility and the total Ho score were used in data analyses. Measures of resting blood pressure, height, weight, and adiposity were also obtained. In men and women, both measures of hostility were positively associated with cholesterol intake and vigorous physical activity. Among women, both hostility measures were positively related to animal fat intake and negatively related to fiber intake. The composite measure was positively related to their resting systolic pressures. Among men, both hostility measures were positively related to cigarette smoking and sugar intake and negatively associated with systolic blood pressure and calcium intake. Findings are discussed in terms of previous research linking hostility to lifestyle behaviors and CAD. PMID- 1591442 TI - The Type A belief system: relationships to hostility, social support, and life stress. AB - Certain core beliefs may underlie the Type A behavior pattern, predisposing individuals to health problems and impaired interpersonal relationships. Previous studies have revealed that the Type A Cognitive Questionnaire (TACQ), a self report measure reflecting these beliefs, is indeed related to emotional distress. The current study assessed the TACQ's relationship to aspects of the interpersonal environment, including perceived social support and stressful events. It also investigated the TACQ's relationship to subtypes of hostility (ie, cynicism and paranoid alienation). Subjects were 111 college undergraduate volunteers. As hypothesized, the TACQ was significantly related to poor quality of social support and to greater perceived life stress. The TACQ appeared more strongly related to cynicism than to paranoid alienation. Findings were generally more pronounced for males. The discussion suggests that Type A beliefs may predispose individuals to health problems through impaired interactions with their interpersonal environment. PMID- 1591443 TI - Aerobic fitness level (VO2max) moderates the increased cardiovascular function and basal thromboxane formation of young healthy Type A males. AB - The authors evaluated the interaction between physical fitness and Type A behavior on vascular production of prostacyclin and platelet thromboxane in response to a standard vessel injury. Ninety-seven male university students were classified as Type A or B on the basis of the Structured Interview of Rosenman. Reactivity, as measured by changes in systolic blood pressure (SBP), and heart rate (HR), measured before and after a stressful Stroop task 1 week later, showed that Type A individuals were more reactive to the stressor than Type Bs, providing independent confirmation of the behavioral interview assessment procedure. Fitness level was determined by a graded treadmill test and was not different for Type As and Type Bs. Basal thromboxane production, measured as the primary metabolite, thromboxane B2, in blood oozing from the bleeding-time site, was highest among unfit Type A subjects. Fit Type As and Type Bs showed significantly lower thromboxane production. No significant differences in prostacyclin production were seen. This study marks the first time that behavior pattern has been linked to an adverse aspect of a thrombosis-related parameter likely to be involved in the genesis of cardiovascular disease. The present results also indicate that physical fitness may, in some fashion, ameliorate the "toxic" effects of Type A behavior. PMID- 1591444 TI - Psychological attributes of participants and nonparticipants in a worksite health and fitness center. AB - This study examined differences in psychological attributes (eg, estimation of physical ability, attraction to physical activity, self-motivation, and attitudinal commitment to physical activity) among 646 participants and nonparticipants in an onsite health and fitness program. An analysis of the data, using stepwise multiple regression and controlling for age and sex, revealed that the psychological attributes significantly predicted group membership (R2 = .27). Increased participation was related to higher levels of attitudinal commitment (beta = .48) and self-motivation (beta = .16). Increased participation, however, was inversely related to estimation of physical ability (beta = -.17). Results of the stepwise multiple discriminant analysis showed that nonparticipants and high active participants could be classified using the predetermined variables with an accuracy of 32.7% and 40.1% gain above base rate, respectively. Low active and moderately active participants were classified at a rate only equal to chance. The authors discuss implications for programming strategies to increase participation in onsite programs. PMID- 1591445 TI - Psychological factors in healing: a new perspective on an old debate. PMID- 1591446 TI - A kinetic model of the agglutination process. AB - We propose a kinetic model of the aggregation process in a system consisting of two different types of particles. Aggregating particles (cells) are polyvalent and bear on the surface a huge number of binding sites for the other type of particles, ligands. The ligand is bivalent and has two identical active sites for binding to cells. The cross-linking of the cells by the ligands causes the aggregation phenomenon called agglutination. We obtained the analytical solution of this model task describing the time dependence of the aggregate mean size versus the composition of the system. The comparison of the analytical solution with the experimental data for the agglutination of bacterial cells by bivalent antibodies shows that the main factors affecting agglutination were correctly taken into account. PMID- 1591447 TI - A measure of spacing in one dimension. PMID- 1591448 TI - Symmetries of S-systems. AB - An S-system is a set of first-order nonlinear differential equations that all have the same structure: The derivative of a variable is equal to the difference of two products of power-law functions. S-systems have been used as models for a variety of problems, primarily in biology. In addition, S-systems possess the interesting property that large classes of differential equations can be recast exactly as S-systems, a feature that has been proven useful in statistics and numerical analysis. Here, simple criteria are introduced that determine whether an S-system possesses certain types of symmetries and how the underlying transformation groups can be constructed. If a transformation group exists, families of solutions can be characterized, the number of S-system equations necessary for solution can be reduced, and some boundary value problems can be reduced to initial value problems. PMID- 1591449 TI - The effect of preferential mixing on the growth of an epidemic. AB - The spread of infection in a community stratified into classes, where individuals have a preference for either within- or between-class contact, is discussed. The effect of such classification is assessed through the comparison of heterogeneous epidemic models with corresponding homogeneous models. Stratification of the community is modeled via a multitype branching process approximation to the epidemic. This allows us to conveniently study its effect through such quantities as the epidemic threshold parameter and the probability of a major outbreak. Attention is focused on the model of May and Anderson; however, a number of other heterogeneous structures reflecting preferential mixing are also studied. PMID- 1591450 TI - On using Lehmann alternatives with nonresponders. AB - The problem of testing for treatment effect when some subjects in the treatment group may be unaffected by the treatment is considered. A form of the Lehmann alternative suggested by Conover and Salsburg is used that assumes that each control score has the same distribution as the minimum of the known number of responses in the treatment group. It is shown that the locally most powerful test leads to a test statistic that, under the hypothesis of no treatment effect, is the sum of independent pareto random variables whereas under the alternative hypothesis it is the sum of independent random variables from a mixture of two pareto distributions. The limiting distribution of the test statistic under both hypotheses is in the domain of attraction of a stable distribution whose indices are derived. The power of the test is given, and its properties are discussed. A set of data from clinical research involving development of a new drug is used to show application of the procedure and demonstrate its usefulness. PMID- 1591451 TI - A theoretical analysis of interval drug dosing for cell-cycle-phase-specific drugs. AB - A formal method is provided for predicting the effect on treatment efficacy of cell-cycle-phase-specific drugs, such as the AIDS drug zidovudine (AZT) or the cancer drug cytosine arabinoside (ara-C). Our analysis shows that the elimination of somatic cells or viruses depends not only on the drug's pharmacokinetic and pharmacodynamic properties, but also the duration of the dosing interval per se and on the life-cycle parameters, that is, the duration of the drug-susceptible life phase, the duration of the whole life cycle, and the proliferation rate. The results support those of simplified models in showing that drug toxicity to the host may be minimized when the dosing interval is an integer multiple of the average cycle time of the host susceptible cells. This prediction has been verified in mice treated with AZT or ara-C. PMID- 1591452 TI - Effect of different kinds of dietary casein on blood cholesterol and triglycerides in pair fed rats. AB - After casein intake, serum cholesterol levels are dependent on many experimental conditions in rats. The effect of the method of casein preparation was assessed in Wistar rats pair-fed for 4 wk with three identical diets differing only by the type of casein used. Compared with dietary casein and Na caseinate, ingestion of lipid- and vitamin-free casein resulted in higher liver weights (4.35 +/- 0.23 vs. 3.89 +/- 0.30 and 3.90 +/- 0.25 g) and fasting serum cholesterol levels (0.55 +/- 0.13 vs. 0.49 +/- 0.09 and 0.44 +/- 0.09 g/L). Compared with the two other casein diets, ingestion of Na caseinate produced the lowest fasting serum triglyceride levels (0.62 +/- 0.13 vs 0.74 +/- 0.12 and 0.73 +/- 0.13 g/L). Peptic digestibility of caseins used might be a regulating factor of serum cholesterol levels in Wistar rats. PMID- 1591453 TI - Relationship between malnutrition and falls in the elderly. AB - Due to the multifactorial nature of falls in the elderly population, it is difficult to determine causal relationships for risk factors for falls. In some cases, other risk factors may play a role. For example, the association between poor nutrition status and falls has not been studied extensively. The association of commonly demonstrated nutritional deficiencies in the elderly with factors such as balance, gait, and mobility may lead to new insights into causes of falls in the elderly not previously established. In this article, we review how malnutrition can be a risk factor for falls, how falls can induce malnutrition, and the possible relationship between mobility and nutrition in the elderly. PMID- 1591454 TI - Representative samples. PMID- 1591455 TI - Magnitude of the host nutritional responses to infection. 1977. PMID- 1591456 TI - Comprehensive nutritional assessment: the dietitian's contribution to the team effort. PMID- 1591457 TI - Riboflavin status of nutritionally supported multiple-trauma accident patients. AB - This study evaluates riboflavin status of multiple-trauma accident patients receiving nutritional support. Riboflavin excretion, erythrocyte glutathione reductase (EGR-AC), erythrocyte riboflavin (ERC-B2), nitrogen balance and riboflavin, and nitrogen and energy intake were assessed periodically throughout the study. Mean intakes of nitrogen, energy, and riboflavin were less than recommended. All patients but one were in negative nitrogen balance; however, patients retained riboflavin except when nitrogen and energy intakes were very low. EGR-AC values were within normal range and did not reflect changes in riboflavin retention. ERC-B2 values were also within normal range but decreased over time in patients with the largest riboflavin excretion and most negative nitrogen balance. ERC-B2 in combination with riboflavin intake and excretion data may offer a suitable method for assessing riboflavin status in multiple-trauma patients. PMID- 1591458 TI - Reported dietary intakes of patients with insulin-dependent diabetes mellitus: limitations of dietary recall. AB - Reported dietary intakes were assessed in young patients with insulin-dependent diabetes mellitus (IDDM). We studied 44 IDDM patients (24 males, 20 females, mean +/- SD age 13.2 +/- 4.5 yr) and compared them with 44 healthy age- and sex matched control subjects. Estimated intakes from 24-h dietary recall were analyzed in relation to body weight and degree of diabetes control. The reported energy intake of the IDDM patients with greater than 120% ideal body weight (IBW) for height was 66, 59/88% (where X = geometric mean, L1 = lower confidence limit/L2 = upper confidence limit) of recommended daily allowance (RDA), whereas those with IBW less than 120% reported 90, 67/120% (p less than 0.01). Patients with increased weights in comparison with IBW had higher hemoglobin A1c (HbA1c) levels (11.9 +/- 2.7%) than those with weights more appropriate for IBW (9.7 +/- 2.4%, p less than 0.025). IDDM patients reported overconsumption of protein and fat, but their carbohydrate intake was low. Analysis of dietary recalls revealed high protein intake (X +/- SD, 20.0 +/- 5.0% of total calorie intake), especially in older (27 +/- 4%) compared with younger (19 +/- 2%-19 +/- 4%, p less than 0.01) patients. Proportions of carbohydrate, protein, and fat did not correlate with variations in body weight and/or HbA1c. The reported intake of protein per kilogram body weight was not significantly different between appropriate-weight and overweight IDDM patients. There was no significant difference in reported total energy intakes of IDDM patients compared with their healthy control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591459 TI - Vitamin E supplementation and oxidative status of peripheral blood mononuclear cells and lymphocyte subsets in hemodialysis patients. AB - Increased oxidative damage to cell membrane constituents causes profound changes in the membrane cytoarchitecture and modifications of the membrane physiological properties, e.g., the ability to respond to hormonal stimuli. In uremic patients receiving intermittent hemodialysis, a metabolic block of the phosphate pentose shunt has been described. This leads to insufficient detoxication of the hydroxyl radicals formed within the cells and therefore to increased oxidative damage to the polyunsaturated fatty acid constituents of the cell membranes. Vitamin E is known to reduce this oxidative damage and its harmful effects. We studied vitamin E (alpha-tocopherol acetate) administration in 10 chronically uremic patients receiving intermittent hemodialysis for positive effects on cell membrane receptor response. The patients were studied before and after treatment for the extent of oxidative damage in peripheral mononuclear cells and for response to monoclonal antibodies to specific markers of T-lymphocyte subsets. After vitamin E treatment, oxidative damage decreased, and the membranes of peripheral mononuclear cells contained greater amounts of some unsaturated fatty acids. This is in agreement with a modification of the membrane phenotype markers of T lymphocyte subsets and seems to confirm in vivo that changes in membrane structure first induced by increased oxidative damage due to the blockage of the phosphate pentose shunt can be reduced by the antioxidant action of vitamin E, which significantly influences the expression of membrane determinants. PMID- 1591460 TI - Long-term stability of lipid emulsions with parenteral nutrition solutions. AB - The stability of the mixture of peripheral vein parenteral nutrition (PN) solution with 10% lipid emulsions (Intralipid or Lipofundin MCT) was tested during a prolonged period of refrigerated storage. The analysis included gross visual examination of the bottle, pH determination, and examination by electron microscope. The mixtures of fat emulsions with PN solution demonstrated no physical instability or pH alteration. Examination under electron microscope revealed no alterations after 4 wk, but the surface layer of fat globules was disrupted after 10 and 18 wk. This study demonstrates that complete nutritive mixtures can be prepared and stored in refrigeration for at least 4 wk before clinical use. PMID- 1591461 TI - Loop diuretics and asthma. PMID- 1591462 TI - Quantification of metoprolol beta 2-adrenoceptor antagonism in asthmatic patients by pharmacokinetic-pharmacodynamic modelling. AB - An integrated pharmacokinetic-pharmacodynamic model was used to quantify the beta 2-blocking activity of metoprolol in seven asthmatic patients. The patients received a subcutaneous dose of terbutaline on two consecutive days. On day 1 they were pretreated with placebo and on day 2 with metoprolol 150 mg orally. Beta 2-adrenoceptor mediated changes of plasma potassium and FEV1 were related to plasma concentrations of terbutaline and racemic metoprolol. Metoprolol activity was measured as the competitive (blocking) interaction of racemic metoprolol on the terbutaline response. Plasma concentrations and effects were monitored over 7 h following terbutaline administration. Despite the relative beta 1-selectivity of metoprolol, the effects of terbutaline were considerably attenuated. The mean (racemic) metoprolol concentration that corresponds to 50% maximum metoprolol receptor occupancy (IC50) for the effects on FEV1 and hypokalemia were, respectively, 17 (+/- 8) and 22 (+/- 12) ng/ml and were not statistically discernible. We conclude that individual integrated pharmacokinetic pharmacodynamic modelling of the concentration-effect relations of agonist and antagonist is a feasible and direct method of quantifying beta 2-blocker effects in asthmatic patients. In stable asthma patients receiving therapeutic doses of metoprolol, the terbutaline plasma concentration needs to be increased two- to four-fold to obtain the same effect on FEV1. Plasma potassium may be considered an appropriate alternative parameter to predict the effect on FEV1. PMID- 1591463 TI - The effect of oral terfenadine on the sensitivity of the cough reflex in normal volunteers. AB - Antihistamines have been reported to have antitussive actions in allergic rhinitis which may be due to an effect of the drug on the cough reflex. We have studied the effect on induced cough in normal volunteers. Ten volunteers inhaled capsaicin at concentrations between 0.78 and 200 microM, in increasing dose order, until they coughed more than five times. The challenge was performed three times before and three times each at 2 and 4 h after 120 mg terfenadine or matched placebo tablet in a double-blind, randomized, cross-over study. Neither affected the capsaicin cough challenge. Thus, any antitussive effect of terfenadine is more likely to be via an indirect mechanism such as inhibition of released histamine rather than on the cough reflex itself. PMID- 1591464 TI - Lung injury induced by paraquat, hyperoxia and cobalt chloride: effects of ambroxol. AB - The effects of the surfactant stimulating drug ambroxol were studied in rats given paraquat (PQ, 15 mg/kg, s.c.), intratracheal cobalt chloride (CoCl2, 2.5 or 1.25 mg Co/kg) or exposed for 2 days to oxygen (greater than 95% O2). Ambroxol (50 mg/kg, i.p., twice daily) was given as a pretreatment for 4 days, or up to 7 days following pneumotoxic administration. Besides body weight evolution and lethality, various pulmonary indices were measured 2 days (O2) or 3 days (PQ and CoCl2) and 7 days after pneumotoxic treatment: wet and dry lung weight, total cell count, distribution of inflammatory cells and lactate dehydrogenase in bronchoalveolar lavage fluid, and histological damage assessed by a semiquantitative injury score. Neither form of ambroxol treatment prevented the toxicity of any of the pneumotoxic agents. The use of a combination of different indices of lung damage showed that different pneumotoxic agents may cause quite distinctive patterns of injury. PMID- 1591465 TI - Histamine H1-receptors mediate endothelium-dependent relaxation of rat isolated pulmonary arteries. AB - Histamine has been reported to cause endothelium-dependent relaxation of vascular smooth muscle and vasodilation. This study was undertaken to examine the inhibitory effects of histamine on cylindrical segments of extrapulmonary arteries isolated from male Sprague Dawley rats. In arterial segments precontracted with phenylephrine (10 microM), histamine (0.1-100 microM) elicited concentration-dependent relaxation responses. Removal of the endothelium or pretreatment with methylene blue (10 microM) abolished relaxation responses to low concentrations of histamine and markedly inhibited those caused by histamine at concentrations greater than 1 microM. Incubation of endothelium-intact arterial segments with pyrilamine (1 microM) caused a significant rightward shift of the histamine concentration-response curves. Treatment of the segments with cimetidine (100 microM) or indomethacin (10 microM) only minimally antagonized histamine-induced relaxation in arteries with endothelium. Residual relaxation responses observed in arteries stripped of endothelium were unaffected by pretreatment with cimetidine, indomethacin, or pyrilamine. The results suggest that the inhibitory effect of histamine in rat pulmonary arteries is mediated predominantly by activation of H1-receptors on the endothelium and the subsequent release of endothelium-derived relaxing factor(s). PMID- 1591466 TI - Stimulation of human airway epithelial cells by platelet activating factor (PAF) and arachidonic acid produces 15-hydroxyeicosatetraenoic acid (15-HETE) capable of contracting bronchial smooth muscle. PMID- 1591467 TI - Effect of acute and chronic moderate hypoxia on the kinetics of lidocaine and its metabolites and on regional blood flow. AB - The effect of acute and chronic hypoxia on the disposition of lidocaine and its metabolites, and on regional blood flow has been examined in conscious beagles (n = 5). Each dog received an infusion of lidocaine for 5 h under three experimental conditions: (1) breathing air; (2) following acute exposure to a FIO2 of 8% and a FICO2 of 3.5% to generate a PaO2 of 45 mmHg without hypocapnia; and (3) after 6 days of hypoxemia. Multiple blood samples were drawn to assess the kinetics of lidocaine and its metabolites, monoethylglycinexylidide (MEGX) and glycinexylidide (GX). Three hours after the end of the infusion of lidocaine, the dogs received radioactive microspheres to estimate hepatic, renal and brain blood flow. Neither acute nor chronic moderate hypoxia affected the kinetics of lidocaine, the parent compound. However, both experimental conditions increased plasma concentrations of MEGX and GX and increased the ratio of the area under their plasma concentration curves to the dose of lidocaine received. Acute moderate hypoxia increased brain blood flow, although it did not affect liver or renal perfusion. Chronic moderate hypoxia did not significantly change the blood flow to any of the organs studied. It was concluded that acute and chronic moderate hypoxia decreases the rate of elimination of both active metabolites of lidocaine without modifying the perfusion to the organs responsible for their elimination. PMID- 1591468 TI - Bias in news reporting. PMID- 1591469 TI - Small n research designs in reproductive toxicology. PMID- 1591470 TI - Reproductive toxicity of chronic lead exposure in the female cynomolgus monkey. AB - The effect of chronic lead (Pb) exposure on menstrual function and circulating concentrations of luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P4) were studied in female nulliparous cynomolgus monkeys (n = 32). Pb acetate (1500 micrograms/kg BW/day) was administered by capsule to monkeys in teh following groups; exposure from birth to 10 years (lifetime, n = 8), postnatal day 300 to 10 years (adolescent, n = 8), and postnatal days 0 to 400 (childhood, n = 8). Monkeys in the control group (n = 8) received gelatin capsules containing the vehicle only. Reproductive assessment of these monkeys was performed between 9 and 10 years, during which time the blood Pb levels in the lifetime and adolescent exposure groups were approximately 35 micrograms/dL. No overt signs of Pb-induced toxicity were found in the general health or menstrual function. However, Pb treatment significantly suppressed circulating levels of LH (P less than 0.042), FSH (P less than 0.041), and E2 (P less than 0.0001) during the menstrual cycle. Pb treatment had no effect on plasma concentrations of P4. These data indicate that chronic Pb exposure results in subclinical suppression of circulating concentrations LH, FSH, and E2 without producing overt signs of menstrual irregularity. PMID- 1591471 TI - Morphometric assessment of the murine ovarian toxicity of 7,12 dimethylbenz(a)anthracene. AB - 7,12-Dimethylbenz(a)anthracene (DMBA) is a polycyclic aromatic hydrocarbon and a component of cigarette smoke that has been identified as a murine reproductive toxicant. The morphometric parameters of total ovarian volume, individual corpus luteum volumes, and total corpora lutea volume were measured in C57BL/6N mice treated with DMBA. Each group received single intraperitoneal injections of 0, 0.1, 1.0, or 10 mg/kg and were sacrificed at 1, 2, 3, or 4 weeks after treatment. DMBA produced a dose-dependent decrease in ovarian volume and number of corpora lutea in each ovary. The observed reduction in total corpora lutea volume did not fully account for the loss in total ovarian volume. This is consistent with previous descriptions of a toxic effect on all ovarian components including growing and resting follicles. Growing follicles that escaped the toxic effects of DMBA and achieved ovulation resulted in a corpus luteum that appeared histologically normal. Morphometric analysis of this animal model further defines the dynamic changes in the mouse ovary in response to DMBA. PMID- 1591472 TI - Effects of dimethyl sulfone (DMSO2) on early gametogenesis in Caenorhabditis elegans: ultrastructural aberrations and loss of synaptonemal complexes from pachytene nuclei. AB - The free-living nematode Caenorhabditis elegans has been used extensively for studies in developmental and reproductive genetics. Recently, toxicologic studies have been initiated using specific sex chromosome mutations. In the present study, high incidence of male (him) mutants, him-5 and him-8, were treated with dimethyl sulfone (DMSO2), the primary metabolite of dimethyl sulfoxide (DMSO). In addition to differential effects on X-chromosome nondisjunction, loss of viability and fertility were observed. Much lower concentrations of DMSO2 were required to elicit the same aberrational effects characteristic of DMSO (1); thus, the toxicity of the former was significantly more potent. The observed decrease in life span was associated with senescent morphology of meiotic prophase nuclei, such that nuclei from young and old specimens could not be differentiated. Aging in oocytes at pachytene is characterized by nucleo cytoplasmic aberrations, increased density of the nucleoplasm and cytoplasm, and decrease in numbers of mitochondria. Increasing concentrations of DMSO2 resulted in a corresponding decrease in fertility and increased production of abnormal gametes. At DMSO2 concentrations higher than 1.0%, synaptonemal complexes (SC) were absent from pachytene nuclei; thus, effective pairing and segregation of homologous chromosomes was prohibited. Since the SC is essential for regulating pairing and subsequent separation of bivalents, the lack of an SC explains the loss of fertility, due to the production of unbalanced gametes, observed in DMSO2 treated specimens. PMID- 1591473 TI - Antagonism of cocaine-induced fetal anomalies by prazosin and diltiazem in mice. AB - Cocaine-induced uteroplacental and fetal vasoconstriction have been observed to cause fetal hypoxemia. The ability of cocaine to elevate norepinephrine (NE) levels has been proposed as one mechanism to explain the effect of cocaine on fetal development. Prazosin, a selective antagonist of alpha-1 adrenergic receptors, and diltiazem, a calcium channel blocker, were used to determine if antagonism of NE-induced vasoconstriction would reduce the effects of chronic cocaine administration on fetal development. The dose-response relationship of cocaine with fetal development was established in CF-1 mice by administering cocaine sc on days 5 to 18 of gestation followed by teratologic evaluation. Cocaine 2 mg/kg/day produced a significant incidence of fetal anomalies without significantly affecting food consumption or maternal and fetal weight gain. In subsequent experiments, prazosin (0.03, 0.3 mg/kg) or diltiazem (1.7, 5.1 mg/kg) were administered po 2 h prior to 2 mg/kg cocaine sc (gestation days 5 to 18) followed by teratologic evaluation. Diltiazem (5.1 mg/kg) produced a significant increase, whereas prazosin (0.3 mg/kg) produced a significant reduction, in the incidence of fetal anomalies compared with saline controls. While data from the pretreatment studies were inconclusive, comparisons between cocaine alone and the cocaine groups pretreated with the high doses of either prazosin or diltiazem seem worthy of further study with larger sample sizes. PMID- 1591474 TI - Spermatogenesis and reproductive performance following human accidental exposure to bromine vapor. AB - The present study was undertaken to evaluate spermatogenesis and reproductive performance among 8 men and their spouses following accidental exposure to bromine vapor. Of the three cases with oligo-terato-asthenozoospermia (OTA), one had been diagnosed prior to and unrelated to the event. Mild OTA and unimpaired reproductive performance characterized the other two cases. Plasma levels of the follicle stimulating hormone and luteinizing hormone were normal in all men. One first-trimester abortion and one late abortion (due to chorioamnionitis) occurred among the 5 pregnancies conceived shortly after the accident. Results of the present study suggest a mild degree of spermatogenic suppression and impaired reproductive performance following paternal exposure to bromine vapor during the above described accident. However, due to the small size of the study cohort, a confidential cause-result linkage could not be established. PMID- 1591475 TI - Intrauterine diethyltoluamide exposure and fetal outcome. AB - The CNS toxicity of the insect repellent, diethyltoluamide (DEET), has been documented by several publications on severely affected adults and children. We report a 4-year-old boy with mental retardation, impaired sensorimotor coordination, and craniofacial dysmorphology, whose mother applied DEET daily throughout her whole pregnancy in addition to the prophylactic use of chloroquine. PMID- 1591476 TI - A maxim whose time is passed. PMID- 1591477 TI - Handling surveillance types of data on birth defects and exposures during pregnancy. PMID- 1591479 TI - Passage of methoxychlor in milk and reproductive organs of nursing female mice; 1. Light and scanning electron microscopic observations. AB - To determine whether the pesticide methoxychlor can be excreted in milk, lactating mouse dams received 14 daily intraperitoneal injections of either sesame oil, or 10.0 micrograms of 17-beta estradiol, or 1.0, 2.0, or 5.0 mg of technical grade methoxychlor. At 15 days, suckling female pups were sacrificed and the effects of the chemicals in milk on the morphology of the immature reproductive tract were examined. The stimulatory changes in both the vagina and uterine horns indicate that the estradiol or methoxychlor doses were excreted in milk and remained biologically active in the suckling mice. Although the stimulatory changes from estradiol or methoxychlor were similar, the higher methoxychlor doses produced some cellular atypia in uterine horns. The possible consequences of early stimulatory influence of methoxychlor on adult reproductive organs are discussed in the text. PMID- 1591478 TI - Reversible and persistent consequences of copper deficiency in developing mice. AB - The effect of maternal copper (Cu) deficiency on various proteins was studied to determine if the changes were reversible or persistent with Cu repletion. The functional consequences of these alterations were assessed by exposing the animals to an oxidative stress (endotoxin), and by measuring the formation of benzo[a]pyrene-DNA adducts in vitro. Throughout gestation and lactation, mice were fed a Control diet (10 micrograms Cu/g diet) or a Low Cu diet (1 microgram Cu/g diet). On day 18, the offspring were killed or switched to the Control diet and killed on day 42 following a single injection of saline or endotoxin on day 41. In day-18 offspring, Cu deficiency resulted in decreased hematocrit values, ceruloplasmin activity, liver and tissue Cu levels, and metallothionein concentrations. Cu repletion restored all but metallothionein levels. Early Cu deficiency led to higher brain CuZn superoxide dismutase activity on day 42, and higher levels of brain thiobarbituric acid reactive substances (TBARS) in endotoxin-treated mice. Liver TBARS were lower in day-18 Low Cu offspring and in day-42 Low Cu offspring treated with endotoxin than age-matched Controls. Cytochrome P-450 concentrations were lower in Low Cu, endotoxin-treated males than in Controls. These results show that Cu deficiency-mediated alterations during early development are not immediately reversed with Cu repletion. PMID- 1591480 TI - Adrenocortical toxicity of 3-methylsulphonyl-DDE; 3: Studies in fetal and suckling mice. AB - Irreversible binding and toxicity of the DDT metabolite 3-methylsulphonyl-DDE (MeSO2-DDE) were examined in fetuses and suckling pups following administration to pregnant or lactating C57Bl mice. Tape-section autoradiography showed a high and tissue-specific accumulation and binding of MeSO2-DDE-14C-derived radioactivity in the late gestational fetal adrenal cortex. According to microautoradiography an irreversibly bound residue was confined to the zona fasciculata. Similarly, there was a high concentration of irreversibly bound 14C labelled material in the adrenal zona fasciculata of suckling pups. Intraperitoneal injection of MeSO2-DDE-14C to lactating mice resulted in higher concentrations of radioactivity in the liver and stomach contents (milk) of the suckling pups than in the maternal liver. This treatment also resulted in a higher level of radioactivity in the adrenals of the pups than in the maternal adrenals, both at a subtoxic and at a toxic dose. Histopathologic examination of adrenals from suckling pups revealed extensive vacuolation and necrosis of the zona fasciculata 2 days following a single dose of MeSO2-DDE (25 mg/kg) to the dam. In the fetal adrenal zona fasciculata, slight degenerative changes were observed following a maternal dose of 50 mg/kg. In conclusion, the study shows that MeSO2-DDE is a highly tissue-specific toxicant to the fetal and postnatal adrenal zona fasciculata in mice. Based on the present data and on previous results in adult mice, we propose that a tissue-specific activation to a reactive metabolite in the fetal and postnatal adrenal cortex is mediated by cytochrome P 450 (11 beta). PMID- 1591481 TI - Effects of maternal exposure to trichloroethylene (TCE) on cell proliferation in the mouse preimplantation embryo. AB - Pregnant mice were treated with trichloroethylene (TCE) at doses ranging from 0.01 micrograms/kg body weight to 483 mg/kg body weight when embryos were traversing the pronuclear stages of development. No treatment-related effect was seen on total number of embryos recovered from oviducts at the 2 to 4 cell stage of development. The 4-cell embryos were tested for cellular proliferative disadvantage by the embryo chimera assay in which embryos from treated mothers (experimental embryos) are paired with embryos from nontreated mothers (control embryos) to form aggregation chimeras. No significant cell proliferation decreases were observed for any of the experimental embryos across all doses examined. PMID- 1591482 TI - Bromodeoxyuridine leaves evidence of prenatal exposure in the postnatal skeleton in CD-1 mice. AB - Mice from two series of experiments (S1, S2) involving intraperitoneal (ip) injection of dams with 300 (High or H), 60 (Low or L), or 0 (VEH) mg 5' bromodeoxyuridine (BUDR) per kilogram body weight (mg/kg) in water (15 mL/kg) on day seven (D7), day eight (D8), or in S2 only, day nine (D9) of gestation (9DPC), and untreated (UNTD) controls, were examined between 60 and 65 days postnatal (DPN) for 88 variations of the skeleton. In S1, 65 variants occurred, and in S2 there were 58 variants that occurred. Substantial numbers of significant differences (P less than 0.01) in frequency of occurrence (%) were seen in High dose only. The number of variants that differed from UNTD were 13, 13, 12, 15, and 11 in S1-D7H, S2-D7H, S1-D8H, S2-D8H, and S2-D9H, respectively; the average absolute difference in frequency among significantly affected variants was 16% to 20%. In the same order as above, 13, 12, 8, 10, and 9 variants differed significantly from VEH, and 9, 8, 7, 8, and 8 variants differed significantly from both UNTD and VEH. In contrast, 0, 0, 1, 1, and 0 variants differed from both UNTD and VEH in S1-D7L, S2-D7L, S1-D8L, S2-D8L, and S2-D9L, respectively. Agreement between the two series was good; 11 traits were affected in High dose litters in both series in at least 3 or 4 comparisons (compared with UNTD, VEH, in S1, S2).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591483 TI - Course of pregnancy and fetal outcome following maternal exposure to carbamazepine and phenytoin: a prospective study. AB - This prospective study followed the pregnancy course of epileptic women at the Motherisk Program of The Hospital for Sick Children, Toronto. We compared fetal outcome of women treated with carbamazepine (CBZ), those treated with diphenylhydantoin (phenytoin, DPH), and a drug-free control group. Seizures were reported in 15 pregnancies; in a subgroup of 9 women without change in drug or schedule, an increase in seizure frequency was evident in 6, a decrease in 1, and no change in 2, regardless of the drug taken. Of 23 children exposed to CBZ in utero, one was born with a lumbar myelomeningocele and multiple congenital anomalies. Of 21 children exposed to DPH, there was one case of severe developmental delay and four with minor features of fetal hydantoin syndromes (FHS). The three groups did not differ in birth weights or gestational ages of the babies. Although much more experience is needed, as a result of this study and other similar reports, Motherisk now offers women treated with CBZ diagnostic tests to detect neural tube defects during the second trimester of pregnancy. PMID- 1591484 TI - Eye abnormality in Drosophila melanogaster exposed to 5-fluorouracil during development. PMID- 1591485 TI - Methods for assessing rat sperm motility. AB - Computer-assisted sperm analysis (CASA) systems are becoming more widely used. With this spread of technology come more data from toxicology studies, designed to determine if treatment with putative toxicants affects sperm motion parameters. While these CASA methods provide us with more ways to evaluate toxicity and thus perhaps increase our chances of successfully protecting human health, there is also a greater likelihood that different laboratories will use different methods of collecting data on sperm motility. Different systems used with different methods in different laboratories will inevitably generate data that are difficult to compare. In a prospective attempt to address this issue of comparability and limit the problems, a group of individuals using CASA systems to analyze rat sperm motility convened to discuss methodologic issues, share data, and try to reach a consensus about methods for performing these studies. This article shares those meetings and data in the hope that common methods will enhance interlaboratory comparisons. PMID- 1591486 TI - Laboratory methods for assessing human semen in epidemiologic studies: a consensus report. AB - It is clear that additional methodologic work needs to be performed. Some data gaps described above are being actively investigated. Other standards were not addressed at this meeting; statistical handling of the data, differences among CASA machines, and factors to consider as potential confounders in analysis are just a few. These may be the subject of future workshops, which will also review progress made in the existing knowledge base. For now, this effort represents a first attempt to share information and to use it to encourage investigators in different laboratories to employ similar methods. In this way more direct comparisons among studies can be made, and our collective data base can be strengthened. PMID- 1591487 TI - Some contributions of the plant kingdom to transfusion medicine--lectins and plant enzymes. PMID- 1591488 TI - Transfusion-associated graft-versus-host disease and blood irradiation. PMID- 1591489 TI - Factor IX concentrates: the new products and their properties. PMID- 1591490 TI - International Symposium on Recombinant Factor VIII: report of the proceedings. PMID- 1591492 TI - The nurse as the primary health-care practitioner. PMID- 1591491 TI - Human erythrocyte glycophorins: protein and gene structure analyses. AB - Human RBCs glycophorins are integral membrane proteins rich in sialic acids that carry blood group antigenic determinants and serve as ligands for viruses, bacteria, and parasites. These molecules have long been used as a general model of membrane proteins and as markers to study normal and pathological differentiation of the erythroid tissue. The RBC glycophorins known as GPA, GPB, GPC, GPD, and GPE have recently been fully characterized at both the protein and the DNA levels, and these studies have demonstrated conclusively that these molecules can be subdivided into two groups that are distinguished by distinct properties. The first group includes the major proteins GPA and GPB, which carry the MN and Ss blood group antigens, respectively, and a recently characterized protein, GPE, presumably expressed at a low level on RBCs. All three proteins are structurally homologous and are essentially erythroid specific. The respective genes are also strikingly homologous up to a transition site defined by an Alu repeat sequence located about 1 Kb downstream from the exon encoding the transmembrane regions. Downstream of the transition site, the GPB and GPE sequences are still homologous, but diverge completely from those of GPA. The three glycophorin genes are organized in tandem on chromosome 4q28-q31, and define a small gene cluster that presumably evolved by duplication from a common ancestral gene. Most likely two sequential duplications occurred, the first, about 9 to 35 million years ago, generated a direct precursor of the GPA gene, and the second, about 5 to 21 million years ago, generated the GPB and GPE genes and that involved a gene that acquired its specific 3' end by homologous recombination through Alu repeats. Numerous variants of GPA and GPB usually detected by abnormal expression of the blood group MNSs antigens are known. An increasing number of these variants have been structurally defined by protein and molecular genetic analyses, and have been shown to result from point mutations, gene deletions, hybrid gene fusion products generated by unequal crossing-over (not at Alu repeats), and microconversion events. The second group of RBC membrane glycophorins includes the minor proteins GPC and GPD both of which carry blood group Gerbich antigens. Protein and nucleic acid analysis indicated that GPD is a truncated form of GPC in its N-terminal region, and that both proteins are produced by a unique gene called GE (Gerbich), which is present as a single copy per haploid genome and is located on chromosome 2q14-q21.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1591493 TI - Paneurhythmy: dancing into wholeness. PMID- 1591494 TI - The art of women as leaders. PMID- 1591495 TI - Numbers versus needs. PMID- 1591496 TI - Predicting adaptive behaviour of severely and profoundly mentally retarded children with early cognitive measures. AB - A longitudinal study was conducted to determine the ability of the Uzgiris and Hunt scales to predict adaptive behaviour including, but not limited to, language. The Uzgiris and Hunt scales, six of the ABS domains and the Receptive Expressive Emergent Language (REEL) scale were administered to 61 children who were severely or profoundly mentally retarded. The ABS domains and the REEL were readministered 4 years later. The findings generally supported earlier cross sectional research and theory. However, this methodology permitted the finding that the earlier score on the ABS domain or REEL was by far the best single predictor of the later score on that same measure, an intuitively obvious, but nevertheless, important finding. The findings were interpreted regarding their implications for theory, practice and methodology. PMID- 1591497 TI - Living in hospital and hostel: the pattern of interactions of people with learning difficulties. AB - This study compared interactions between the staff and residents living in hospital wards and in community-based hostels. Twenty-four people with moderate to severe learning difficulties participated in this study. Interactions were categorized according to who was the initiator and recipient, their purpose, attitude of the recipient, duration, and place. It was found that the hospital and hotel residents had virtually no interactions with people outwith the establishment in which they lived. The hostel appeared to offer the residents a sociable environment with more interpersonal interactions and more positive attitudes towards the interactants than the hospital. Interactions in both kinds of setting were very short, thus giving residents little chance to develop communicative skills. It is suggested that a more personal approach, such as joint activities between residents and staff, and living in small groups in ordinary housing, should be the first priorities in the effort to improve the pattern of social interactions of people with moderate to severe learning difficulties. PMID- 1591498 TI - A study of the relationship of community living situation to independence and satisfaction in the lives of mentally retarded adults. AB - This study examined the relationship between the level of supervision provided at the community residences of 61 adults with mental retardation and their sense of independence and satisfaction in specific aspects of home life, work and community activity. Responses given to interview questions were transformed into scores for independence and satisfaction for each subject. In order to compare the relationship of supervision at home, an individual's intellectual functional ability, and his social support to independence and satisfaction, non-parametric analyses of the data were performed. These revealed statistically significant inverse relationships between the degree of home supervision and independence both at home and within the community, and satisfaction at home. Greater functional ability was found not to be significantly related to any measures of independence or satisfaction. A high level of social support was correlated only with overall measures of community independence, satisfaction at home, and community satisfaction. PMID- 1591499 TI - Teaching skills through the enhancement of natural antecedents. AB - The manipulation of the natural antecedents of a task offers a potentially valuable alternative to teaching strategies requiring the presentation of additional prompting stimuli, particularly in work with individuals with severe learning difficulties. The utility of procedures involving the enhancement of natural antecedents has frequently been demonstrated, but this has generally been with respect to tasks of limited ecological validity. This study reports an attempt to teach coat-buttoning skills to two women with severe learning difficulties using an antecedent enhancement procedure. Manipulation of the natural antecedents of coat buttoning produced swift acquisition of the required component responses in both subjects. Further, these skills generalized successfully across both materials (other coats) and time (6-month follow-up). Such antecedent enhancement procedures may be of particular value to the extent that they offer a consistent means of presenting subtle, interactive interventions without requiring advanced teaching skills on the part of staff. PMID- 1591500 TI - Anger, depression and self-concept in adults with mental retardation. AB - Self-report measures of anger, depression and self-concept that were designed for non-retarded children were adapted for adults with mental retardation. The measures were administered to 130 adults with mental retardation who lived in the community. Informants rated the subjects on shortened forms of the three emotional indices. Informant self-concept ratings were negatively correlated with ratings of anger and depression. On the self-report measures, subjects who reported low self-concept also reported high levels of depression. Mildly mentally retarded subjects were more likely to report anger than severe/moderately retarded subjects. Informant and self-report measures were significantly correlated for self-concept and depression, but not for anger. The results provide preliminary normative data on indices of emotional adjustment for community-based adults with mental retardation. PMID- 1591501 TI - Development of diurnal bladder control in severely and profoundly mentally handicapped residents. AB - At two time points, separated by an interval of 7 years, the level of diurnal bladder control of 198 severely and profoundly mentally handicapped individuals was assessed. A slight, but statistically significant increase of bladder control between the two time points was found. Difference scores of level of control were submitted to an ANOVA. Age at admission and duration of institutionalization proved to be related to individuals' level of diurnal bladder control. The results were discussed in relation to the use of toilet training procedures with mentally handicapped individuals. PMID- 1591502 TI - The use of a low phenylalanine diet with amino acid supplement in the treatment of behavioural problems in a severely mentally retarded adult female with phenylketonuria. AB - If phenylketonuria is untreated in infancy, it causes irreversible brain damage. No dietary treatment can alter this brain damage. However, it has been shown that dietary treatment can reduce behaviour disturbances often associated with the condition. In this study, a subject's behaviour was monitored over 18 weeks while on a low phenylalanine diet. Results demonstrate a significant reduction in the level of her disturbed behaviour. PMID- 1591503 TI - Clinical relevance of albuminuria in hypertensive patients. AB - Albuminuria (including the form not detectable by conventional tests, i.e., microalbuminuria) as well as renal dysfunction have recently been recognized as important complications in the patient with essential hypertension. The presence of albuminuria predicts cardiovascular events. Albuminuria is associated with more severe hypertension, with evidence of more advanced target organ damage (e.g., left ventricular hypertrophy), and is more prevalent in high-risk groups (e.g., the elderly). On the other hand, albuminuria may also be associated with generalized endothelial barrier dysfunction and thus predispose to accelerated atherogenesis. Ischemic nephropathy from nonmalignant nephrosclerosis has emerged as an important cause of terminal renal failure in the elderly patient with essential hypertension. PMID- 1591504 TI - Influence of antihypertensive therapy on renal function. AB - Antihypertensive therapy influences kidney function by different mechanisms depending on the mode of action of the drug used. The GFR is improved by calcium entry blockers and ACE inhibitors, unaffected by vasodilators, alpha-blockers and centrally acting sympatholytics and impaired by beta-blockers. The same is true for renal blood flow and is due to changes of renal vascular resistance. Renal sodium excretion is impaired mostly by vasodilators, by alpha-blockers, sympatholytics and beta-blockers; in contrast, calcium entry blockers and ACE inhibitors acutely induce natriuresis. The RAAS is stimulated by vasodilators, unaffected by alpha-blockers and sympatholytics and suppressed by beta-blockers. Plasma catecholamines are stimulated by vasodilators and suppressed by centrally acting sympatholytics and unaffected by the others. Induction of acute renal functional impairment is reported for ACE inhibitors under conditions of compromised renal perfusion pressure such as in renal artery stenosis. These data from the literature reviewed are supported by our own experimental data on sodium balance under different drugs and micropuncture data in experimental renal artery stenosis. To achieve effective antihypertensive treatment with a low profile of side effects, careful monitoring of renal function seems to be mandatory. PMID- 1591505 TI - What blood pressure levels should be treated? AB - Information concerning the level of blood pressure at which treatment should be commenced is incomplete, and current guidelines have to be considered of provisional suggestions on which many experts have a consensus. There is general agreement on the need to administer anti-hypertensive therapy when diastolic pressure is 100 mmHg or above. At diastolic values of 90-99 mmHg the risk, albeit increased, is relatively low. The wisest practical solution, which coincides with guidelines from the World Health Organization and the International Society of Hypertension, is to commence treatment if diastolic pressure is between 95 and 100 mmHg, but only after several months of observation with repeated measurements. At values between 90 and 95 mmHg, a decision in favor of treatment will be influenced by concomitant elevation of systolic values and by the occurrence of other risk factors or a strong family history of cardiovascular disease. PMID- 1591506 TI - Shock tactics and the myth of the inverted U. PMID- 1591507 TI - Conversation with Charles Fletcher. PMID- 1591508 TI - The validity of self-reported drug use. AB - Response errors in self-reported drug questionnaires are evaluated, with particular reference to incidence and prevalence estimates. A simple model of response errors is defined, and some analytical results are obtained from this model. By assuming independence of response errors at different points in time, estimates for response errors are obtained from panel data. The results suggest that while the frequency of false negatives may be larger than the frequency of false positives, the latter error may nevertheless produce large errors in prevalence estimates, particularly if the prevalence rate is small. PMID- 1591509 TI - A feminist critique of problem gambling research. AB - Using a liberal feminist orientation, the literature on a diverse range of topics concerning the profile of the pathological gambler, from personality traits to psychiatric orientation, as well as consequences of the behavior on individuals was reviewed for its gender-related content. The vast majority of this research has been on male subjects; gender of respondents has not been discussed; gender related findings have not been reported; mostly male-dominated gambling sites have been investigated. To say that most compulsive gamblers are men and therefore, theorists need to explain them first and only later apply these same explanations to the 'rare' [female] cases is to acquiesce to a patriarchal notion of the world. Action is suggested which would put a halt to this trend and suggestions are made for future research. PMID- 1591510 TI - Persuading general practitioners to prescribe--good husbandry or a recipe for chaos? AB - Edinburgh's Community Drug Problem Service was set up three years ago in response to the high prevalence of HIV infection amongst local injecting drug users and the lack of existing statutory drug services in Lothian. From the outset, a policy of shared care and substitute prescribing by the druguser's general practitioner (GP) was adopted. Over 800 referrals later, this discussion paper looks at the methods used to persuade GPs to cooperate in longterm drug management, and examines the advantages, disadvantages and outcome of such a shared care approach. PMID- 1591511 TI - Sex and the risk of HIV infection: the role of alcohol. AB - To investigate sexual behaviour under the influence of alcohol and the relationship between drinking habits and unsafe sex we carried out a postal and interview survey of 2174 students in the North East of England. Drinking habits were classified as non, light, medium and heavy, and cross-tabulated against sexual and other risk taking behaviour. Response rates of 74% and 77% were obtained in the postal and interview surveys respectively. In the postal survey, heavier drinkers were more likely to have unsafe sex such as casual sex without a condom, and sex with someone know to have many partners. Respondents associated alcohol with sexual risk taking; because of drinking too much, in the last year, 19% had not taken contraceptive precautions during sex. The interview survey largely confirmed postal survey results. There are three possible explanations of the association between drinking habits and unsafe sex: alcohol might disinhibit safer sex; young risk-takers may also drink more; or, drinking might be associated with unsafe sex by coincidence because sexual encounters often begin in licensed premises. Drinking habits should therefore be a priority issue for future HIV/AIDS related research, policy debate, and health education endeavour. PMID- 1591512 TI - Changes in HIV risk behaviors among intravenous drug users in San Juan, Puerto Rico. AB - Strategies for reaching intravenous drug users (IVDUs) not in treatment and reducing risk behaviors are urgently needed to reduce the human immunodeficiency virus (HIV) epidemic. Of special concern is the need to detect which types of risk behaviors are more likely to change and which are resistant to change. The present paper analyzes changes occurring in HIV transmission risk behaviors among 778 IVDUs not in treatment, in the city of San Juan, Puerto Rico. Results show discontinuation rates of risk behaviors to be substantial. Discontinuation rates of injection equipment sharing practices varied from 33% in shared use of cookers to 74.2% in sharing needles with strangers. Drug injection and use of shooting galleries were also reduced, although to a lesser extent (8.5% and 19.3% respectively). Among protective behaviors, use of new needles was found to increase nearly twice as much as the use of bleach (20.6% vs. 11.3% respectively). The results suggest the need to understand the factors facilitating/inhibiting change in specific behaviors and the need to study the stability of these changes over longer periods of time. PMID- 1591513 TI - Test-retest stability of cardiovascular and subjective responses to intravenous cocaine in humans. AB - Sixteen male i.v. cocaine users were measured on their cardiovascular and subjective responses to placebo followed on a separate day by 40 mg i.v. cocaine injections. They were retested within 2 weeks, again receiving placebo and 40 mg i.v. cocaine injections in a random order on separate days. Significant increases in baseline (pre-injection) heart rates during the later sessions were interpreted as possibly reflecting conditioning effects. There were no significant differences in post-injection increases in cardiovascular or subjective responses between the initial and later 40 mg conditions, which might have been indicative of tolerance or sensitization development. Test-retest correlations, indicative of response stability, were moderate to high for any particular timepoint for blood pressure, heart rate, and subjective responses, but pre- vs. post-injection change scores were stable across testings on these measures only under placebo. With the possible exception of some subjective responses, there was little evidence of test-retest stability in responses (change scores) to the 40 mg cocaine injection. PMID- 1591514 TI - The Temptation and Restraint Inventory for measuring drinking restraint. AB - In the present study, the measurement of drinking restraint was broadened by developing new items that better characterized its cognitive nature as well as by testing a factor structure which represents restraint as including both the regulation and the failure to regulate alcohol intake. A previously observed (Collins, George & Lapp, 1989) three-component structure of the Restrained Drinking Scale (RDS; Ruderman & McKirnan, 1984) was confirmed. In addition, two factors were extracted from the new set of cognitive items, which when combined with the RDS clusters formed a new measure of drinking restraint, the Temptation and Restraint Inventory (TRI). The factor structure of the TRI matched the conceptualization of drinking restraint as involving successful and unsuccessful regulation of alcohol intake, and differentially predicted self-reported weekly consumption and alcohol-related problems. PMID- 1591515 TI - Substance misuse and social work qualifying training in the British Isles: a survey of CQSW courses. AB - In 1989, all Certificate of Qualification in Social Work (CQSW) courses in the British Isles were included in a survey of the training offered social work students on responding to psychoactive substance misuse. There was a 74% response rate. Eleven per cent of the courses that responded provided no formal substance misuse training. Those that offered training provided a median of 8 hours, with over 70% of students receiving less than 11 hours, indicating that many students were being given the briefest of overviews. Outside of four or five 'centres of excellence', social workers and probation officers training in 1988-89 received less than adequate preparation to work with people with alcohol- and drug-related problems, despite evidence that they account for a large and growing proportion of their caseloads. PMID- 1591516 TI - Changes in levels of alcohol consumption: United States, 1983-1988. AB - Using data from the 1983 and 1988 National Health Interview Surveys, this note examines changes both in the prevalence of abstention and the prevalence of heavier drinking among drinkers in the United States. Changes are examined separately by gender and according to other sociodemographic characteristics often associated with different levels of alcohol consumption. Results suggest an increase in abstention and a decrease in heavier drinking between 1983 and 1988. For women, decreases in heavier drinking were found among those 18-44 years of age, among those employed, and among those divorced/separated or never married. For men, decreases in heavier drinking were found among those employed, among those with family income of $25,000 or more, and among those married or divorced/separated. Changes both in abstention and heavier drinking were found to vary considerably by geographical region. These findings do not support results from other general population survey studies on alcohol use that suggest a stability in drinking levels, or even a slight increase in heavier drinking among men. PMID- 1591517 TI - On pseudo-patrons and pseudo-training for bar staff. PMID- 1591518 TI - Outreach to injecting drug users and female sexual partners of drug users on the lower east side of New York City. AB - In 1984, outreach to injecting drug users and their female sexual partners was initiated as part of HIV behavioral research projects. HIV, health, drug treatment and family planning information and services were provided in addition to recruiting subjects to the research program. Such outreach also poses certain problems--especially potential disruption of neighborhood day-to-day life and clashes with police. This paper discusses an outreach program to injecting drug users and their female sexual partners that was initiated in New York City to provide HIV-related information and services. We examine the successes of the program and problems that were involved in conducting outreach to persons who are typically not accessible through formal institutional channels. PMID- 1591519 TI - Who should receive methadone maintenance? AB - The aim of this study was to evaluate the assessment policies of a regional unit established to process requests for entry to several long-term methadone maintenance programmes. The factors which led staff to reject an applicants request for methadone maintenance were retrospectively analysed from assessment records. Analysis indicated that the decision to reject applicants had been based on the judgement that they were not physically dependent on opioids; other factors favouring rejection included less involvement in crime, youth, and short duration of drug use. Eighty-four applicants who had either been rejected (n = 58) or failed to complete the assessment (n = 26) were followed. At follow-up, more than half of the subjects had entered methadone programmes, usually after a long delay. Four subjects had achieved a degree of stable abstinence. The remainder were continuing to use illicit drugs, or were in treatment or prison. Four subjects had died. We conclude that: (1) our criteria for excluding people from treatment were based on the perceived need to keep non-addicted people from maintenance treatment; and (2) such a policy in practice served to prolong the applicants' illicit drug use and delay their entry to treatment. PMID- 1591520 TI - Passive smoking--some further legal issues for employers. AB - In the past year there have been several important developments concerning passive smoking including the publication of two authoritative books; two important UK cases which will affect all future personal injury claims for passive smoking and the first successful passive smoking claim for State Accident Disablement Benefit. Worldwide, the Australia Federal Court confirmed that there is unequivocal scientific evidence that passive smoking is harmful to health. This judgement is particularly significant for the UK as it was the testimony of two leading experts, Professor Nicholas J. Wald and Sir Richard Doll, whose evidence helped convince the Judge about the harmful health effects of passive smoke. Within the European Community several newly-adopted Directives may well require employers to adopt a more rigorous approach to smoking restrictions. In particular, an EC Resolution in 1989 requires Member States to ban smoking in all public places. This has been given important legal backing by the European Court of Justice which may force Member States to adopt the Resolution whether they like it or not! Other measures concerning tobacco products are currently being reviewed by the Commission. PMID- 1591521 TI - Alcohol consumption among unemployed youths: results from a prospective study. AB - A prospective study, including all 1083 pupils in the final year of compulsory schooling in a municipality in northern Sweden, was performed. Ninety-seven point nine per cent of the pupils were followed up after five years. They completed a comprehensive self-administered questionnaire including questions on alcohol consumption. Among men a positive correlation between long-standing unemployment (greater than 20 weeks) and alcohol consumption at the beginning and at the end of the study, as well as the change in consumption during the follow-up period was seen. This correlation was still present when earlier alcohol consumption and socioeconomic variables were controlled for. In women there was a positive correlation between unemployment and the level of alcohol consumption, but a negative correlation between unemployment and change in consumption. When controlling for motherhood and alcohol intake at the start of the study the correlation turned positive. Unemployment among women did not seem to affect recruitment to the high consumption group. Our results support the suggestion that unemployment may be a risk indicator for increasing alcohol consumption among young people, particularly in young men. PMID- 1591522 TI - Positive and negative consequences of alcohol drinking among young university students in Finland. AB - In a sample of 1663 female and 707 male Finnish university students in their first study year, the female students reported less negative and less positive consequences of alcohol drinking than their male counterparts. The female students also drank less, less frequently and less often for intoxication. However, the profile of negative and positive consequences of drinking was similar for both genders; 74.6% of the female students and 80.0% of the males had more positive than negative experiences from alcohol. Both the positive and negative consequences of drinking correlated positively to alcohol consumption and drinking for intoxication. About half of the students who had many positive consequences of drinking were not heavy drinkers and did not report many negative consequences. Depression, anxiety, stress or psychosomatic symptoms did not correlate with either with positive or negative consequences of drinking, nor with alcohol consumption. Drinking for anxiety, depression, stress or the reduction of tension appeared to be infrequent. Young Finnish university students mostly drink for the positive consequences of drinking. PMID- 1591523 TI - Young adult drinking behaviour: a comparison of diary and quantity-frequency measures. AB - One hundred and twenty-two college students over a 2-week period completed a diary of their drinking habits and reasons for drinking, as well as a structured questionnaire about drinking attitudes and habits. Daily consumption based on the diary was compared with consumption based on a quantity-frequency measure within the questionnaire. There were no significant differences between estimates of consumption based on the two measures, and both measures were highly correlated. The questionnaire was more accurate in classifying drinkers and non-drinkers and led to better identification of those classified as hazardous and harmful drinkers. Sex differences in beliefs about drinking, as well as differences according to drinker classification, were found. Unsafe drinkers rated their drinking episodes as significantly more satisfying, comforting and exciting than other drinkers and were more likely to drink in order to get drunk and to relax. Their beliefs, attitudes and intentions also were more favourable towards the consumption of alcohol. Hotels or clubs were the most preferred locations for beer and spirits consumption while wine was consumed mainly at home. Most drinking took place within a mixed group or with close friends. Findings are discussed in terms of the relative advantages of both diary and quantity frequency/questionnaire methods. PMID- 1591524 TI - Development and validation of a multi-dimensional instrument for assessing outcome of treatment among opiate users: the Opiate Treatment Index. AB - This article presents a new instrument with which to assess the effects of opiate treatment. The Opiate Treatment Index (OTI) is multi-dimensional in structure, with scales measuring six independently measured outcome domains: drug use; HIV risk-taking behaviour; social functioning; criminality; health; and psychological adjustment. Psychometric properties of the Index are excellent, suggesting that the OTI is a relatively quick, efficient means of obtaining reliable and valid data on opiate users undergoing treatment over a range of relevant outcome domains. PMID- 1591525 TI - Development of a short 'readiness to change' questionnaire for use in brief, opportunistic interventions among excessive drinkers. AB - Excessive drinkers (141) identified in medical settings who were not seeking help for an alcohol problem completed a questionnaire based on Prochaska and DiClemente's stages of change model. Principal components analysis revealed a clear factor structure corresponding to the 'precontemplation', 'contemplation' and 'action' stages of change. On this basis, a 12-item 'Readiness to change' questionnaire was developed with satisfactory psychometric properties. As predicted, scale scores on adjacent stages of change showed significantly higher inter-correlations than scores on non-adjacent stages. Concurrent validation by comparison with subjects' choices of cartoons depicting each of the stages of change and with screening questions regarding aspects of drinking behaviour was moderate to very good. The questionnaire provides a short and convenient measure of readiness to change which may be used in conjunction with brief, opportunistic interventions with excessive drinkers. PMID- 1591526 TI - A statistical approach to an alcoholic drinking history. AB - The drinking history of a middle-aged male was analyzed statistically on the basis of eight and a half years of notes on the number of drinks consumed per day. During the period his average number of drinks per drinking day increased from about 7 in 1974 to a peak of about 16 in 1980 while the number of abstinent days varied between 23% and 54% with no clear trend. These figures are of the same magnitude as published reports on drinking among alcoholics. Time-series models of intake or drinking frequency could not describe adequately the time structure of annual or monthly consumption. Occurrence of drinking was analyzed as a random series of events. The time-structure of the series was highly irregular and deviated greatly from the Poisson hypothesis which assumes that each day has an equal probability of becoming a drinking day independently of previous days. Instead, drinking days were clustered into sprees with an average length of 7 days, high variance and a very skew distribution, separated by abstinence periods with an average length of 4 days and a similarly shaped distribution. The entire history could be partitioned into 286 alternating drinking and abstinence intervals, one day intervals included. The drinking rhythm was very stable: no significant trends in the lengths of either type of interval could be found. The main findings are the surprising stability of the drinking rhythm, its independence of the growing amounts consumed, and the independently varying abstinence interval lengths. Even in the absence of reporting and memory bias, such a pattern of drinking may produce very inaccurate recall of the actual long-term alcohol intake, if the recall period is short. The results suggest that periods shorter than one month should be avoided when asking questions about alcohol intake, for example, in research on the effects of treatment on alcoholism or alcohol intake on health. PMID- 1591527 TI - Prevalence estimates of pathological gambling in Seville (Spain). AB - Pathological gambling is becoming an increasing concern for the Spanish population. Governmental figures from 1989 show that in the Autonomic Region of Andalucia, with a population of 7 million inhabitants, more than three hundred billion pesetas (approximately UK pounds 1,500 million) were spent during 1988 gambling in casinos, slot machines and at bingo. These figures represent an increase of 15% over the figures of the previous year and suggest that gambling may have come a very important problem in Spain. This paper presents the first epidemiological study carried out in Spain on gambling and the estimated prevalence of pathological gambling in Seville, political capital of Andalucia. A sample of 598 individuals were interviewed with an adapted screening instrument. The results suggest that further epidemiological studies are required at a national level. They also indicate that preventive and treatment measures should also be taken urgently. PMID- 1591528 TI - Prevalence and predictors of psychopathology among opioid users. PMID- 1591529 TI - Alcohol-related mortality in the United States, 1979-1988. AB - Using alcohol-attributable fractions derived from studies of alcohol's involvement in various causes of death, this report presents trends in overall alcohol-related mortality for each year from 1979 through 1988. Age-adjusted rates show decreases in alcohol-related mortality for both sexes and for whites and nonwhites. Decreases occur for causes of death directly attributable to alcohol and for other diseases and injuries and adverse effects indirectly attributable to alcohol. Issues surrounding the use of currently available alcohol-attributable fractions for estimating alcohol-related mortality are discussed. PMID- 1591530 TI - The effects of co-dependence on physicians and nurses. PMID- 1591531 TI - A local algorithm for DNA sequence alignment with inversions. AB - A dynamic programming algorithm to find all optimal alignments of DNA subsequences is described. The alignments use not only substitutions, insertions and deletions of nucleotides but also inversions (reversed complements) of substrings of the sequences. The inversion alignments themselves contain substitutions, insertions and deletions of nucleotides. We study the problem of alignment with non-intersecting inversions. To provide a computationally efficient algorithm we restrict candidate inversions to the K highest scoring inversions. An algorithm to find the J best non-intersecting alignments with inversions is also described. The new algorithm is applied to the regions of mitochondrial DNA of Drosophila yakuba and mouse coding for URF6 and cytochrome b and the inversion of the URF6 gene is found. The open problem of intersecting inversions is discussed. PMID- 1591532 TI - Analysis of volume regulation in an epithelial cell model. AB - An epithelial cell is modeled as a single compartment, bounded by apical and basolateral cell membranes, and containing two nonelectrolyte solute species, nominally NaCl and KCl. Membrane transport of these species may be metabolically driven, or it may follow the transmembrane concentration gradients, either singly (a channel) or jointly (a cotransporter). To represent the effect of stretch activated channels or shrinkage-activated cotransporters, the membrane permeabilities and cotransport coefficients are permitted to be functions of cell volume. When this epithelium is considered as a dynamical system, conditions are indicated which guarantee the uniqueness and stability of equilibria. Experimentally, many epithelial cells can regulate their volume, and such volume regulatory capability is defined for this model. It is clearly distinct from dynamical stability of the equilibrium and requires more stringent conditions on the volume-dependent permeabilities and cotransporters. For a previously developed model of the toad urinary bladder (Strieter et al., 1990, J. gen. Physiol. 96, 319-344) the uniqueness and stability of its equilibria are indicated. The analysis also demonstrates that under some conditions a second stable equilibrium may appear, along with a saddle-node bifurcation. This is illustrated numerically in a modified model of the epithelium of the thick ascending limb of Henle. PMID- 1591534 TI - An O (N2 log N) restriction map comparison and search algorithm. AB - We present an O (R log P) time, O (M+P2) space algorithm for searching a restriction map with M sites for the best matches to a shorter map with P sites, where R, the number of matching site pairs, is bounded by MP. As first proposed by Waterman et al. (1984, Nucl. Acids Res. 12, 237-242) the objective function used to score matches is additive in the number of unaligned sites and the discrepancies in the distances between adjacent aligned sites. Our algorithm is basically a sparse dynamic programming computation in which "candidate lists" are used to model the future contribution of all previously computed entries to those yet to be computed. A simple modification to the algorithm computes the distance between two restriction maps with M and N sites, respectively, in O (MN (log M+log N)) time. PMID- 1591533 TI - A survey of multiple sequence comparison methods. AB - Multiple sequence comparison refers to the search for similarity in three or more sequences. This article presents a survey of the exhaustive (optimal) and heuristic (possibly sub-optimal) methods developed for the comparison of multiple macromolecular sequences. Emphasis is given to the different approaches of the heuristic methods. Four distance measures derived from information engineering and genetic studies are introduced for the comparison between two alignments of sequences. The use of entropy, which plays a central role in information theory as measures of information, choice and uncertainty, is proposed as a simple measure for the evaluation of the optimality of an alignment in the absence of any a priori knowledge about the structures of the sequences being compared. This article also gives two examples of comparison between alternative alignments of the same set of 5SRNAs as obtained by several different heuristic methods. PMID- 1591536 TI - Depression and the environment. PMID- 1591535 TI - Modeling immune reactivity in secondary lymphoid organs. AB - Models of the dynamical interactions important in generating immune reactivity have generally assumed that the immune system is a single well-stirred compartment. Here we explicitly take into account the compartmentalized nature of the immune system and show that qualitative conclusions, such as the stability of the immune steady state, depend on architectural details. We examine a simple model idiotypic network involving only two types of B cells and antibody molecules. We show, for model parameters used by De Boer et al. (1990, Chem. Eng. Sci. 45, 2375-2382), that the immune steady state is unstable in a one compartmental model but stable in a two compartment model that contains both a lymphoid organ, such as the spleen, and the circulatory system. PMID- 1591537 TI - Pay parity for clinical academics. PMID- 1591538 TI - Are micrometastases clinically relevant? PMID- 1591539 TI - The Schizophrenia Association of Great Britain. PMID- 1591540 TI - The laryngeal mask airway. AB - The laryngeal mask airway is a new development in airway management. It became commercially available in 1988 and has since become an integral part of anaesthetic practice; its potential outside anaesthesia is rapidly developing. This article describes the basic concepts, methods of insertion and applications, current and projected. PMID- 1591541 TI - Nasal ventilation. AB - Intermittent positive-pressure ventilation through a nasal mask is an effective, simple, non-invasive method of domiciliary ventilatory support in patients with chronic respiratory disease. It has recently been used in other situations, including intensive care, and can considerably improve the management of patients with chronic respiratory failure. PMID- 1591542 TI - Primary pneumococcal peritonitis. AB - Primary pneumococcal peritonitis is an uncommon condition which in the preantibiotic era was associated with a high mortality rate. We present two cases and discuss the aetiology, clinical features and management of this condition. PMID- 1591543 TI - Acute upper airway obstruction and septicaemic shock. PMID- 1591544 TI - Falls in the elderly. AB - Falls are a common cause of admission to a geriatric unit, and yet the approach to the elderly faller remains unsatisfactory. This article outlines the epidemiology of falls, the age-related physiological changes that may contribute to the risk of falling and the classification and causes of falls, and discusses the evaluation and management of this problem. PMID- 1591545 TI - Hip replacement surgery. AB - This review describes the current status of hip arthroplasty, hip mechanics, the materials used and the designs of the implants. The aims of and indications for surgery are outlined. Various complications and their prophylaxis are discussed, with particular stress on infection and thromboembolic problems. Results from published series and likely future developments are outlined. PMID- 1591546 TI - Selectively withholding treatment from newborn babies. AB - Whether to withhold life-prolonging treatment from a severely handicapped newborn baby is a topical moral dilemma. Some recent prominent court cases in the UK highlight the ethical issues that have to be faced when considering such a decision. PMID- 1591547 TI - A simple technique for temporary suprapubic catheterization. AB - Temporary suprapubic catheterization is frequently required, often in emergency situations. We describe a simple technique employing a 14 G intravenous cannula and 4 FG feeding tube. The principle can be applied to children and adults. PMID- 1591548 TI - Package inserts. AB - Research has shown that most people would like more information about their medicines. Almost all would welcome the idea of having a printed leaflet if it were written in simple terms. Such leaflets are now being incorporated with medicines which are prescribed in original packs. PMID- 1591549 TI - Pain in children. AB - Children, and particularly neonates, often receive inadequate pain relief after surgery. In this review we describe the important physiological and pharmacological differences between babies and children, and discuss practical aspects of pain assessment and relief. PMID- 1591550 TI - MRCOG Part Two: Facing the viva. AB - The viva examination has two parts: the clinical and the viva voce. This article presents practical advice on how best to approach what is rightly felt by many to be the most hazardous part of the MRCOG Part Two examination. PMID- 1591551 TI - A rare complication of umbilical artery catheterization. PMID- 1591552 TI - Muddled messages about breast cancer. PMID- 1591553 TI - Further advice on insertion of Hickman-type catheters. PMID- 1591554 TI - Adenosine: a must for every casualty department. PMID- 1591555 TI - Designing drugs. PMID- 1591556 TI - Continuous subcutaneous bronchodilators in brittle asthma. PMID- 1591557 TI - Thrombolysis in acute myocardial infarction. AB - Reperfusion of ischaemic myocardium with thrombolytic agents during the early stages of acute myocardial infarction reduces the mortality rate and can limit infarct size with associated sparing of left ventricular function. Effective and safe regimens are now available and in the absence of contraindications thrombolysis should now form part of the standard management acute myocardial infarction. PMID- 1591558 TI - New treatments in inflammatory bowel disease. AB - Salicylates and steroids remain the mainstay of treatment for inflammatory bowel disease. New formulations which attempt to lower the rates of side effects are under evaluation. The value of azathioprine has been established in ulcerative colitis and cyclosporin has been shown to be of value. Dietary therapy in Crohn's disease has been the focus of a large amount of research and benefits have been demonstrated. New therapies including bioengineered drugs are anticipated. PMID- 1591559 TI - Treating a patient with frequent generalized seizures. PMID- 1591560 TI - Artificial urinary sphincters. AB - The use of artificial sphincters for the treatment of urinary incontinence has evolved steadily over the last few decades. Currently available designs are suitable for implantation in male and female patients of all age-groups. This article describes the clinical implications of artificial urinary sphincters in the treatment of incontinent patients. PMID- 1591561 TI - Interrogation and false confessions: vulnerability factors. AB - This paper reviews the psychological factors that make some individuals susceptible to making a false confession of having committed a criminal offence. A number of 'vulnerability factors' are highlighted and it is emphasized that these need to be interpreted within the context of all circumstances surrounding the case. PMID- 1591562 TI - Compulsory HIV testing for surgeons? AB - There is concern that surgeons with human immunodeficiency virus (HIV) infection could transmit it to patients. This article considers the risk of transmission, the official guidance on HIV-infected healthcare workers, and the arguments for and against HIV screening in surgeons. PMID- 1591563 TI - Screening for osteoporosis. AB - Osteoporosis is a prevalent disease without a curative treatment. Agents that will prevent fracture are known and bone mineral density can now be measured. Thus there is a prima-facie case for screening, which should be explored. PMID- 1591564 TI - Instructive cases from genetics. 2. PMID- 1591565 TI - Hypertensive disorders of pregnancy for the trainee. AB - Hypertensive disorders of pregnancy are a leading cause of maternal mortality. Despite this, definitions and management remain controversial. There is increasing evidence that in severe cases outcome may be improved by the use of clearly defined management protocols in centres of special expertise. PMID- 1591566 TI - Fears for the future of academic medicine. PMID- 1591567 TI - Fears for the future of academic medicine. PMID- 1591568 TI - Putting A&E consultants in their place. PMID- 1591569 TI - The role of right hemisphere dysfunction in psychiatric disorders. PMID- 1591570 TI - Innovations in mental health care delivery. AB - In serious mental illness (SMI) even good community care does not usually make a major impact on clinical or social function, but patients and relatives prefer community to hospital care, and it tends to be cheaper. Any gains are lost if the required community services are not resourced, coordinated, and maintained indefinitely. A few SMI patients continue to need asylum under one roof. CPNs see more anxiety/depression than SMI. Their patients come increasingly from GPs, and they tend to work in practices with less need. Their cost-effectiveness is uncertain, although nurse behaviour therapists are cost-effective in anxiety disorders in primary care. Such research is also needed into the work of other mental health professionals. Despite their effectiveness, there is a dearth of behaviour therapists among nurses and psychiatrists. Problem-orientated training is lacking for most professionals with most patients. Behavioural self-treatments have improved phobic disorders and non-severe depression in controlled studies. Gains were as great when self-treatment was guided by a computer or by a manual as by a clinician. Self-help can extend care delivery, with therapists acting as consultants. Computers can also aid clinical audit. PMID- 1591571 TI - Recent developments in expressed emotion and schizophrenia. AB - Expressed emotion (EE) has substantial scientific support as a predictor of relapse of positive symptoms. The median relapse rate in a high-EE environment is 48%, compared with 21% in a low-EE environment. This effect does not seem to be due to confounding with other variables, but it is subject to limitations in its scope of application. EE probably determines relapse through its effect on emotions and symptom control. A stress-vulnerability model of relapse is advanced that incorporates biological factors as well as cycles of mutual influence between symptomatic behaviour, life events, and EE. Aversive types of behaviour in patients and their relatives are seen as understandable reactions to stress that are moderated by social perceptions and coping skills. Families have made positive achievements, including the provision of non-invasive support. PMID- 1591572 TI - Audit of electroconvulsive treatment in two national health service regions. AB - The practice of ECT has been surveyed by visits to all 35 NHS hospitals and five private clinics where it is used in the North East Thames and East Anglian Regions, and observation of ECT administration in 29 NHS and two private clinics. Since 1981 there has been much improvement in the physical conditions in which ECT is given and in anaesthetic practice. Nursing is good or excellent in a majority. About half the clinics have the most effective Ectron constant-current series 5 apparatus; the rest have older models with which 'missed' fits and undertreatment are frequent. Stimulus-dosing is usually by habit rather than rational strategy, and routine instrument settings differ fourfold between clinics. Most hospitals have nominated consultants in charge of ECT, but few of these are closely involved and little has changed in the unsatisfactory training and supervision of those who give the treatment. The use of ECT has fallen by 55% in North East Thames Region since 1979, but has risen by 20% in the East Anglian Region. There are up to 12-fold differences in usage between districts. PMID- 1591573 TI - Blunted prolactin responses to d-fenfluramine in sociopathy. Evidence for subsensitivity of central serotonergic function. AB - Using a neuroendocrine probe we studied nine male offenders in a forensic hospital, convicted of murder, with a diagnosis of antisocial personality disorder, who had been behaviourally 'quiescent' for varying periods and who had not recently been abusing drugs. Nine healthy age-matched men also participated. All subjects received 30 mg d-fenfluramine (d-FEN), a 5-HT releasing agent, orally, after an overnight fast, and serial samples for prolactin estimation were taken hourly for five hours. Responses were significantly impaired in the patients, suggesting a subsensitivity of certain 5-HT systems in antisocial personality disorder, regardless of recent or ongoing behavioural disturbance. PMID- 1591574 TI - Trace elements and the electroencephalogram during long-term lithium treatment. AB - Endogenous bromine has been found to be raised during lithium treatment, and it has been suggested that it may augment the therapeutic effect of lithium. Our findings in a study of 12 patients and 12 controls support this contention. Electroencephalographic effects of bromine, vanadium and aluminium were studied- higher bromine and vanadium levels were associated with irregular cortical activity. Electroencephalographic abnormalities were associated with more side effects of lithium. PMID- 1591575 TI - Central conduction time in childhood autism. AB - To investigate the integrity of the brain-stem in 20 mentally handicapped children who met the Rutter criteria for autism, brain-stem auditory evoked potentials were obtained for a range of stimulus intensities. Central conduction times (CCTs) were calculated for the Wave I-Wave V interval of the brain-stem potentials. In children under 14 years of age CCTs were normal. In children 14 years of age and over, three of four girls and eight of nine boys had CCTs exceeding normal limits when compared with a group of controls of normal intelligence, matched for age and sex. CCTs recorded from a group of non-autistic mentally handicapped children were within normal limits. The age distribution are consistent with a maturational defect in myelination within the brain-stem in autism, a defect which may have a much wider anatomical distribution throughout cortical and subcortical structures. PMID- 1591576 TI - Psychological precursors of panic attacks. AB - The ongoing experience of panic disorder was assessed in 20 female subjects, to determine psychological precursors to panic attacks. Measures of anxiety, threat, control, prediction of panic, and symptoms were assessed at hourly intervals during waking hours for one week. Measures were taken using a portable computerised diary which prompted for and stored responses. Patients' ratings of the prediction of panic attacks were the only significant precursors to panic attacks. This supports recent research that expectancy is important in panic onset. The data also suggested that anxiety levels follow a circadian pattern. PMID- 1591577 TI - An assessment of the educational needs of chronic psychiatric patients and their relatives. AB - Both psychiatric patients and their relatives benefit from learning about mental illness and how to cope with it, but the specific interests of these consumers remain unclear. To determine specific educational needs and to compare the needs of different consumers, a questionnaire survey was conducted with a sample of patients with schizophrenia and affective disorder and their relatives. Both patients and relatives reported strong interest in learning more about psychiatric illness and strategies for coping with common problems, but patients with schizophrenia were less interested than patients with affective disorder and both sets of relatives. Discriminant analyses revealed that needs differed as a function of patient diagnosis, patient/relative status, and relatives' membership of a self-help and advocacy organisation. Consumers of mental health services are capable of specifying their own educational needs, and educational programmes should be tailored to meet these. PMID- 1591578 TI - The natural history of neurotic disorder in an elderly urban population. Findings from the Liverpool longitudinal study of continuing health in the community. AB - A random community sample of 1070 subjects aged 65 years and over was interviewed at home using the GMS-AGECAT package and followed up three years later. Neurotic symptoms were common, but symptoms sufficient to reach 'case' level were much less frequent. The overall prevalence of neurotic 'cases' was 2.4% in year 0 and 1.4% in year 3. The incidence was estimated as a minimum of 4.4 per 1000 per year over the age of 65. Women were more likely to be 'cases' than men but not 'subcases', and there was a general decline in prevalence with increasing age, particularly for 'subcases'. Anxiety was the commonest neurotic subtype. After three years, 'cases' were shown not to persist, but this did not reflect wellness. There was a tendency still to have some symptoms, but the predominant symptom appeared to change, suggesting a possible chronic neurotic disorder with changing presentation over time. Depressive symptoms were closely associated with this presentation, suggesting that depression may be an important and integral part of a general, changing neurotic disorder. PMID- 1591579 TI - The Northfield experiments. AB - The Northfield Experiments took place at Hollymoor Hospital, Northfield, Birmingham, during World War II. The first experiment was conducted by Bion & Rickman. The second evolved gradually; many people contributed to its success, including Foulkes, Main and Bridger. The experiments were an important landmark in the evolution of theory and practice in group psychotherapy and in the therapeutic community movement. They were not carried out solely as responses to the need for mass treatment of neurotic disorders among army personnel; antecedent factors, the theoretical orientation of the practitioners and the nature of army life were equally important. The two experiments differed in pace and in recognition of the needs of higher-order systems, particularly the military hierarchy. They shared many underlying concepts, including responsibility to society, the therapeutic use of groups (including the hospital community) and an emphasis on process. Lessons learned at Northfield remain relevant to the practice of psychiatry today. PMID- 1591580 TI - The first use of lithium? PMID- 1591581 TI - Lithium augmentation in antidepressant-resistant patients. PMID- 1591582 TI - Schizophrenia among Afro-Caribbeans. PMID- 1591583 TI - Schizophrenia among Afro-Caribbeans. PMID- 1591584 TI - Schizophrenia among Afro-Caribbeans. PMID- 1591585 TI - Anorexia nervosa and XY gonadal dysgenesis. PMID- 1591586 TI - Methylfolate and psychiatric illness. PMID- 1591587 TI - Christmas disease and major affective disorder. PMID- 1591588 TI - Survivors of disaster. PMID- 1591589 TI - Late-onset anorexia nervosa. PMID- 1591590 TI - Sexual abuse and referral bias. PMID- 1591591 TI - Screening for depression in the medically ill. PMID- 1591592 TI - Systemic family therapy in adult psychiatry. PMID- 1591593 TI - Service use by Indian immigrants. PMID- 1591594 TI - Seasonal risk factors. PMID- 1591595 TI - Peripheral audiosensitivity. PMID- 1591596 TI - Special medical and nursing care needs of people with severe learning difficulties. PMID- 1591598 TI - Kainic acid differently affects retinal projections to different pretectal nuclei. AB - Kainic acid (KA) damages retinal cells, thus impairing axonal anterograde transport of labeled aminoacids when injected intravitreally. In this study, Long Evans rats were injected with KA into one eye, and seven days later were binocularly injected with 14C-valine. The extent of residual retinal afferents to two pretectal nuclei was calculated as the percentage of the contralateral, intact side. Projections to the nucleus of the optic tract (first relay station of the optokinetic pathway) appear significantly more affected than those to the olivary pretectal nucleus (involved in the pupillary light response). These results suggest a correlation between the functional properties of retinal ganglion cells and distinctive biochemical characteristics, such as their susceptibility to KA. PMID- 1591597 TI - Analgesia inhibitory system involvement in nonacupuncture point-stimulation produced analgesia. AB - Acupuncture analgesia (AA), caused by low-frequency stimulation of an acupuncture point (AP)--in this case the tibial muscle--was augmented. Nonacupuncture analgesia (NAA), caused under certain circumstances by stimulation of a nonacupuncture point (NAP)--in this case the abdominal muscle--was unmasked by lesion in the lateral centromedian nucleus of the thalamus (L-CM) or part of the posterior hypothalamus (I-PH). Stimulation in these regions suppressed the augmented part of the AA and blocked the NAA. These regions were, collectively, given the name analgesia inhibitory system. NAA was abolished, the same as AA, by hypophysectomy. The pathways from the AP and NAP to the pituitary gland were different. AA was naloxone reversible, and NAA was dexamethasone reversible. The analgesia inhibitory system is activated nonspecifically by stimulation of either an AP or NAP. It ascends to the I-PH, thence to the L-CM, and ultimately inhibits the pathway nonspecifically connected to the NAP and AP in the lateral part of the periaqueductal central gray (PAG), without affecting the pathway specifically connected to the AP. Thus, only stimulation of an AP will produce analgesia, whereas stimulation of an NAP will not normally produce analgesia. Stress-induced analgesia (SIA) is produced in a different way than AA or NAA. PMID- 1591599 TI - Differential rearing conditions in rats: effects on neurochemistry in neocortical areas and cognitive behaviors. AB - Previous studies have shown that environmental factors can influence several aspects of the central nervous system that are associated with behavioral changes. In the present study, an attempt was made to investigate how cholinergic and glutamergic transmission systems in neocortical areas might respond to differential rearing conditions and how potential neurochemical changes might be accompanied by alterations in behavior. The results show that only glutamergic levels in the lateral entorhinal cortex (LEC) responded to differential environmental stimulation. The levels of glutamergic activity in LEC correlated significantly with learning and retention of a visual discrimination task and total time exploring objects in a novelty test. A comparatively complex pattern of neurochemical relations was seen in terms of differences across brain structures and hemispheres for both glutamergic and cholinergic activity. The results are interpreted as supporting the glutamergic hypothesis of Alzheimer's disease. PMID- 1591600 TI - Demonstration by in situ hybridization of the proopiomelanocortin gene in the rat heart. AB - A biotinylated oligonucleotide probe was used to demonstrate the presence in the heart of the portion of the proopiomelanocortin messenger RNA which contains the sequence for beta-endorphin. The probe indicated the presence of beta-endorphin messenger RNA in cardiac tissue and specifically in the cardiac muscle cell. The probe also confirmed the well-documented presence of messenger RNA for beta endorphin in the anterior and neurointermediate lobes of the pituitary. These findings indicate that in addition to the pituitary, beta-endorphin is produced in situ in the heart. PMID- 1591601 TI - Organization of amygdaloid projections to brainstem dopaminergic, noradrenergic, and adrenergic cell groups in the rat. AB - The distribution of amygdaloid axons in the various brainstem dopaminergic, noradrenergic, and adrenergic cell groups was examined. This was accomplished by means of the Phaseolus vulgaris leucoagglutinin lectin (PHA-L) anterograde tracing technique combined with glucose-oxidase immunocytochemistry to catecholamine markers (i.e., tyrosine hydroxylase, dopamine beta hydroxylase, and phenylethanolamine N-methyltransferase). Injections of PHA-L in the medial part of the central amygdaloid nucleus resulted in axonal and terminal labeling in most catecholamine cell groups in the brainstem. Amygdaloid terminals appeared to contract catecholaminergic cells in several brainstem regions. The most heavily innervated catecholaminergic cells were the A9 (lateral) and A8 dopaminergic cell groups and the C2/A2 adrenergic/noradrenergic cell groups in the nucleus of the solitary tract. The medial part of the A9 and adjacent A10 dopaminergic cell groups was moderately innervated. A moderate innervation by amygdaloid terminals was observed on rostral locus coeruleus noradrenergic cells (A6 rostral) and adrenergic cells of the rostral ventrolateral medulla (C1). Noradrenergic cells of the A5, main body of the locus coeruleus (A6), A7, and subcoeruleus were sparsely innervated. Amygdaloid axons were not observed on noradrenergic neurons of the A4 cell group, area postrema, and A1 cells of the ventrolateral medulla. The results demonstrate that the amygdala primarily innervates the dopaminergic cells of midbrain (i.e., A8 and lateral A9 cells) and the adrenergic cells (C2) and noradrenergic (A2) cells in the nucleus of the solitary tract. The possible functional significance of amygdaloid innervation of catecholaminergic cells is discussed. PMID- 1591602 TI - Buspirone impairs performance of a three-choice working memory water escape task in rats. AB - Two studies were conducted to assess the effects of buspirone and alprazolam on a three-choice working memory water escape task. Both studies involved giving rats three daily trials, each trial consisting of an information run during which guillotine doors forced the rats to swim into the correct escape alley and a test run during which the rats could enter any of the three alleys but escape only on entering the same alley to which they had been forced on the information run. In the first experiment, rats were trained to a 70% correct choice criterion with 5 min interrun intervals and then tested for performance with 5, 20, 20 with distraction, and 60-min interrun intervals. In the second experiment, rats in each of the drug groups were tested after receiving one of three different doses of their respective drug. Results suggest that 1.0, 3.0, and 10.0 mg/kg buspirone but not 0.5, 1.0, and 2.0 mg/kg alprazolam impaired performance of rats on a three-choice working memory water escape task. PMID- 1591603 TI - Auditory-evoked response of the cortex after yohimbine administration: phase advance effect of central noradrenergic activation. AB - The effects of central noradrenergic activation on an auditory-evoked cortical response were studied using systemic administration of yohimbine (2 mg/kg intravenously, IV), a noradrenergic stimulant, in 13 anesthetized rats. To analyze changes of the response, surface and intracortical evoked potentials (EP) as well as extracellular single-unit recordings with tungsten microelectrodes were employed. It was noted that the initial-positive wave of the surface EP corresponded to unit firing responses in a restricted area of the auditory cortex, where the surface EP was largest and a polarity inversion of the intracortical EP was observed. The following effects were produced by yohimbine: 1) The initial-positive surface potential (n = 10) and corresponding intracortical potential with inverted polarity (n = 6) both showed an increase in amplitude and a decrease in peak latency; 2) the unit firing response (n = 10) tended to show an increase in peak frequency and a decrease in peak firing latency; and 3) yohimbine produced an earlier ending of the firing period, and in paired stimulation experiments (n = 7) it prolonged the period during which the second response was suppressed, indicating an augmentation of postexcitation inhibition. Later histological examination suggested that most of the units recorded were pyramidal cells. These findings indicate that chemical stimulation of the central noradrenergic system by yohimbine enhances both the initial excitatory and following inhibitory processes in the auditory-evoked response of the cortical units (probably pyramidal cells), resulting not only in amplification of the response but also in advancement of the response phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591604 TI - Visual P3-like potentials in squirrel monkey: effects of a noradrenergic agonist. AB - Event-related potentials (ERPs) were recorded from squirrel monkeys (Saimiri sciureus) in a 90-10 visual "oddball" paradigm. A small, blue rectangle was presented every 2 s on 90% of the trials (background), whereas a yellow rectangle occurred on 10% on the trials (oddball). Electrical activity time-locked to these stimulus events was recorded from epidural electrodes before and following systemic administration of the alpha-2 noradrenergic agonist clonidine (0.1 mg/kg intramuscularly, IM). Baseline data in response to oddball stimuli showed a large, P3-like potential exhibiting a fronto-central maximum along midline electrodes and a parietal maximum along lateral electrodes. A frontally dominant, long-latency, negative slow wave (SN) consistently followed this P3-like potential. Amplitudes for P3 were larger following 10% than 50% probable oddball events. These results suggest that monkeys exhibit large, probability-sensitive P3-like potentials similar to the visual potentials reported in humans. Administration of clonidine had no effect on the amplitude, area, or latency of the monkey P3 component. This contrasts with our previous findings that the same dose of clonidine significantly decreases auditory P3s in these monkeys. Such differences may reflect distinct functional roles for norepinephrine in the processing of low-probability acoustic versus visual signals and argues against the hypothesis that norepinephrine is a common neurotransmitter substrate for auditory and visual P3-like potentials. PMID- 1591605 TI - Hypercard-based data management tools for molecular biologists. AB - I have designed a Macintosh data management system for molecular biologists. This system, called DataMinder, can be used to store information about oligonucleotides, nucleic acid or protein sequences, recombinant DNA clones, cells, reagents and protocols. DataMinder is not limited to data storage. A number of utilities for data analysis are provided, including those for the evaluation of oligonucleotides for use as hybridization probes or primers for DNA synthesis, and a variety of sequence editing features. Context-sensitive help is available on-line. DataMinder is simple to use and to customize and allows for sharing of database information across a computer network. PMID- 1591606 TI - On a common structure of intelligence in biological and technical systems. AB - This is a survey of the general structure of an electronic computer-implemented, operation-oriented system, designed by the authors, which uses artificial intelligence mechanisms and is intended for the control of technical objects that function both in predictable and random environments. The system is based on processing knowledge, which is stored in a hierarchically arranged Knowledge Bank, and program mechanisms for adapting to and interacting with the External and Internal Worlds. The system has distributed program mechanisms, which are 'designed' with a constant structure. It is independent of the purpose and environment of the system operation and the specific features of the controlled object. None of the program mechanisms are concentrated in any program module. They are distributed in many modules, and therefore there is no single module responsible for the execution of a particular external function. The system is structured into separate program modules by internal procedures. The conceptual organisation of the Knowledge Base presupposes that the framework is structured according to functional, semantic and tier indications, i.e. the structured description of knowledge, by the system, of the external environment and its possible behaviour in it. The possibility of multiple use of the same elements of the lower tiers of the Knowledge Base by higher-tier elements makes the proposed Knowledge Base very efficient. If the cerebrum is considered at a structural level, there appears to be an amazing similarity between the structure and the mechanisms of the above system and the structure of the cerebral cortex, as suggested previously by Edelman and Mountcastle. Each mechanism of the cerebral cortex structure has a structural analogue in the described system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591607 TI - Statistical distance between texts and filtration methods in sequence comparison. AB - Upon searching local similarities in long sequences, the necessity of a 'rapid' similarity search becomes acute. Quadratic complexity of dynamic programming algorithms forces the employment of filtration methods that allow elimination of the sequences with a low similarity level. The paper is devoted to the theoretical substantiations of the filtration method based on the statistical distance between texts. The notion of the filtration efficiency is introduced and the efficiency of several filters is estimated. It is shown that the efficiency of the statistical l-tuple filtration upon DNA database search is associated with a potential extension of the original four-letter alphabet and grows exponentially with increasing l. The formula that allows one to estimate the filtration parameters is presented. PMID- 1591608 TI - EMBLSCAN: fast approximate DNA database searches on compact disc. AB - An algorithm that allows rapid searching of nucleic acid sequences based on pregenerated index files is described. The programs and index files for searching the entire EMBL nucleotide sequence collection are being distributed on the EMBL Data Library's CD-ROM. PMID- 1591609 TI - Harnessing networked workstations as a powerful parallel computer: a general paradigm illustrated using three programs for genetic linkage analysis. AB - It is widely accepted that parallel computers, which have the ability to execute different parts of a program simultaneously, will offer dramatic speed-up for many time-consuming biological computations. The paper describes how the use of the machine-independent parallel programming language, Linda, allows parallel programs to run on an institution's network of workstations. In this way, an institution can harness existing hardware, which is often either idle or vastly underutilized, as a powerful 'parallel machine' with supercomputing capability. The paper illustrates this very general paradigm by describing the use of Linda to parallelize three widely used programs for genetic linkage analysis, a mathematical technique used in gene mapping. The paper then discusses a number of technical, administrative and social issues that arise when creating such a computational resource. PMID- 1591610 TI - The UK Human Genome Mapping Project online computing service. AB - This paper presents an overview of computing and networking facilities developed by the Medical Research Council to provide online computing support to the Human Genome Mapping Project (HGMP) in the UK. The facility is connected to a number of other computing facilities in various centres of genetics and molecular biology research excellence, either directly via high-speed links or through national and international wide-area networks. The paper describes the design and implementation of the current system, a 'client/server' network of Sun, IBM, DEC and Apple servers, gateways and workstations. A short outline of online computing services currently delivered by this system to the UK human genetics research community is also provided. More information about the services and their availability could be obtained by a direct approach to the UK HGMP-RC. PMID- 1591611 TI - Parallelization of a local similarity algorithm. AB - The local similarity problem is to determine the similar regions within two given sequences. We recently developed a dynamic programming algorithm for the local similarity problem that requires only space proportional to the sum of the two sequence lengths, whereas earlier methods use space proportional to the product of the lengths. In this paper, we describe how to parallelize the new algorithm and present results of experimental studies on an Intel hypercube. The parallel method provides rapid, high-resolution alignments for users of our software toolkit for pairwise sequence comparison, as illustrated here by a comparison of the chloroplast genomes of tobacco and liverwort. PMID- 1591612 TI - Comparing machine-independent versus machine-specific parallelization of a software platform for biological sequence comparison. AB - A platform program that performs biological sequence comparison provides a case study to compare the relative advantages of a machine-independent approach to parallel computation versus a machine-specific approach. The program consists of two routines: (i) PSCANLIB, which compares a single biological sequence against a database of sequences, and (ii) PCOMPLIB, which compares a database of sequences against another database of sequences, or against itself. The program was first parallelized to run on the Intel Hypercube parallel computer using native Hypercube commands to coordinate the parallel computation. The parallelization logic of the program was then translated into a machine-independent parallel programming language, Linda. These two approaches to parallelization are contrasted in terms of: (i) the expressive power of the logic that coordinates the parallel computation, (ii) the portability of the machine-independent version to other parallel machines and (iii) the relative efficiency of the two versions of the program. In the benchmark tests reported, the benefits of the machine independent approach were achieved with only a modest sacrifice in efficiency. PMID- 1591613 TI - DNA Translator and Aligner: HyperCard utilities to aid phylogenetic analysis of molecules. AB - DNA Translator and Aligner are molecular phylogenetics HyperCard stacks for Macintosh computers. They manipulate sequence data to provide graphical gene mapping, conversions, translations and manual multiple-sequence alignment editing. DNA Translator is able to convert documented GenBank or EMBL documented sequences into linearized, rescalable gene maps whose gene sequences are extractable by clicking on the corresponding map button or by selection from a scrolling list. Provided gene maps, complete with extractable sequences, consist of nine metazoan, one yeast, and one ciliate mitochondrial DNAs and three green plant chloroplast DNAs. Single or multiple sequences can be manipulated to aid in phylogenetic analysis. Sequences can be translated between nucleic acids and proteins in either direction with flexible support of alternate genetic codes and ambiguous nucleotide symbols. Multiple aligned sequence output from diverse sources can be converted to Nexus, Hennig86 or PHYLIP format for subsequent phylogenetic analysis. Input or output alignments can be examined with Aligner, a convenient accessory stack included in the DNA Translator package. Aligner is an editor for the manual alignment of up to 100 sequences that toggles between display of matched characters and normal unmatched sequences. DNA Translator also generates graphic displays of amino acid coding and codon usage frequency relative to all other, or only synonymous, codons for approximately 70 select organism-organelle combinations. Codon usage data is compatible with spreadsheet or UWGCG formats for incorporation of additional molecules of interest. The complete package is available via anonymous ftp and is free for non-commercial uses. PMID- 1591614 TI - MOMENT: software for analysis and display of amphiphilic regions in proteins. AB - MOMENT is a 53 kbyte program written in Borland TurboPascal with Borland Turbo Graphics, which will run on IBM PC-compatible machines. The program reads protein sequence files and calculates the hydrophobic moment of user-defined segments. The values produced can be displayed in the form of a scan through the sequence, as vector diagrams and helical wheels, as plots of hydrophobic moment versus hydrophobicity, or as hydrophobic moment as a function of angle. PMID- 1591615 TI - CLUSTAL V: improved software for multiple sequence alignment. AB - The CLUSTAL package of multiple sequence alignment programs has been completely rewritten and many new features added. The new software is a single program called CLUSTAL V, which is written in C and can be used on any machine with a standard C compiler. The main new features are the ability to store and reuse old alignments and the ability to calculate phylogenetic trees after alignment. The program is simple to use, completely menu driven and on-line help is provided. PMID- 1591616 TI - Fluorescent automated DNA sequencers: a file exchange program. PMID- 1591617 TI - REF-LIST: program to list references found in DOS text files of scientific manuscripts. AB - A computer program, coded in QuickBASIC language, is used to make a non-redundant list of references, in alphabetical order, that are found in a scientific manuscript (formatted as a DOS text file). The program can extract either direct or indirect citations as in the following: Byers (1983a, b, 1984) and Miller and Keen, 1960; Byers et al., 1984; Byers 1984) An IBM-compatible personal computer is required to run the executable program. PMID- 1591618 TI - Alerting users to relevant new entries in the GenBank DNA sequence database. PMID- 1591619 TI - An investigation of the epidemiology of neuroblastoma in children under the age of 15 years in England, Scotland and Wales. AB - Neuroblastoma is the third commonest tumour of childhood in the UK, having an incidence rate of 1 in 10,500. Incidence and mortality rates were calculated for the whole of the United Kingdom for a period of at least 10 years. The effects of age, stage and regional health authority at diagnosis, year of birth, year of diagnosis and sex on the incidence and mortality rates were determined. Incidence was found to vary with age and stage at diagnosis, and there was a significant interaction between age and stage. A difference in incidence between the sexes was also discovered. Mortality was found to vary with age and stage at diagnosis, although no interaction was found. The finding that mortality has fallen in recent years may be an artefact due to recent records being necessarily incomplete. Survival statistics were calculated for the UK and certain European cases, and the effects on survival of age, stage, region at diagnosis and sex were determined. Survival varied with age and stage at diagnosis, region of diagnosis and sex, although it was only possible to demonstrate significant differences between certain of the stages. It was impossible to test for any interaction term by the methods used. PMID- 1591620 TI - A tissue culture model for studying ethanol toxicity on embryonic heart cells. AB - A tissue system in which fibroblasts and myocytes from chick embryonic hearts were separately maintained was used to study the toxicity of ethanol. To reproduce the teratogenic effects of acute, high concentrations of ethanol typical of "binge" drinking, an open tissue culture system was employed. With open cultures, the cells were initially exposed to peak alcohol levels for approximately 6 hr and were exposed to decreasing concentrations of ethanol for the remainder of each 24 hr period. After the first day of ethanol exposure, there was substantial cell loss in both fibroblast and myocyte cultures. Alcohol induced cell loss was dose-dependent. Despite decreased cell density after the first day of ethanol exposure, the surviving cells differentiated into monolayers of fibroblasts or beating cardiac muscle fibers. However, both ethanol-exposed fibroblasts and myocytes appeared atrophic, that is, smaller and shrunken. Electrophoretic analysis or these ethanol-exposed fibroblast and myocyte cultures revealed specific reduction in the cellular contents of alpha-actinin, myosin, and actin. These decreases in cytoskeletal proteins may be responsible for the morphological abnormalities noted in these cells. PMID- 1591621 TI - S-adenosyl-L-methionine reverses the cholestatic effect of ethinylestradiol in rat hepatocytes by increasing its catabolism. AB - In this study, ethinylestradiol inhibited the uptake of taurocholate by cultured rat hepatocytes, increasing the Km while leaving the Vmax unchanged. S-Adenosyl-L methionine (SAMe) had no effect on taurocholate uptake or release, but was able to reverse the competitive inhibition induced by ethinylestradiol. S-Adenosyl-L homocysteine did not reverse this inhibition, which suggests that the methyl group of SAMe affects its activity. Several possible mechanisms for the action of SAMe were investigated. The methylation of cell membrane phospholipids was eliminated as a possible mechanism. The presence of SAMe greatly increased the catabolism of ethinylestradiol by hepatocytes and reduced its covalent binding to hepatocyte macromolecules. In culture supernatants, both highly polar (conjugated) and non-conjugated metabolites could be detected. Moreover, most of the metabolites were methylated. This suggests that SAMe may revert the effects of ethinylestradiol of taurocholate uptake by increasing its catabolic rate by hepatocytes. PMID- 1591622 TI - Culture of cells from zebrafish (Brachydanio rerio) embryo and adult tissues. AB - The zebrafish is a popular model for studies of vertebrate development and toxicology. However, in vitro approaches with this organism have not been fully exploited because cell culture systems have been unavailable. We developed methods for the culture of cells from blastula-stage diploid and haploid zebrafish embryos, as well as cells from the caudal and pelvic fin, gill, liver, and viscera of adult fish. The haploid embryo-derived cells differentiated in culture to a pigmented phenotype and expressed, upon exposure to 2,3,7,8 tetrachlorodibenzo-p-dioxin, a protein that was immunologically and functionally similar to rainbow trout cytochrome P450IA1. Zebrafish cultures were grown in a complex basal nutrient medium supplemented with insulin, trout embryo extract, and low concentrations of trout and fetal bovine serum; they could not be maintained in conventional culture medium containing a high concentration of mammalian serum. Using calcium phosphate-mediated transfection, a plasmid constructed for use in mammalian cells was introduced into zebrafish embryo cell cultures and expressed in a stable manner. These results indicated that the transfection procedures utilized in mammalian systems can also be applied to zebrafish cell cultures, providing a means for in vitro alteration of the genotype and phenotype of the cells. PMID- 1591623 TI - The effect of K+/H+ antiporter nigericin on gap junction permeability. AB - The K+/H+ antiporter nigericin inhibits the intercellular exchange of the fluorescent dye Lucifer Yellow between DM15-transformed fibroblasts derived from the Djungarian hamster. The efficacy of nigericin action was related to its concentration and time of incubation. The nigericin-induced uncoupling effect on gap junctions was reversible and was shown to be based on its ability to cause cystolic acidification. The effect of nigericin on dye-coupling in intact and 12 O-tetradecanoyl-phorbol-13-acetate (TPA)-pretreated cells did not differ, indicating that the uncoupling effect of H+ on gap junctions in DM15 cells was not mediated by the TPA-dependent isoform of protein kinase C. PMID- 1591624 TI - Effect of bromodeoxyuridine on the proliferation and growth of ethyl methanesulfonate-exposed P3 cells: relationship to the induction of sister chromatid exchanges. AB - Although sister-chromatid exchange (SCE) analysis is recognized as an indicator of exposure to DNA-damaging agents, the results of these analyses have been confounded by the use of bromodeoxyuridine (BrdUrd) to differentially label the sister chromatids. Not only does BrdUrd itself induce SCE, it also modulates the frequency of SCE induced by certain DNA-damaging agents. In order to examine this effect of BrdUrd on SCE frequency, an indirect method which lends itself to measurements both with and without BrdUrd was employed. Human teratocarcinoma derived (P3) cells were exposed to ethyl methanesulfonate (EMS) and cultured with increasing concentrations of BrdUrd for lengths of time corresponding to one, two, and three generations of cell growth. At each time point, the distribution of nuclei among the phases of the cell-cycle and cell growth were evaluated for each concentration and chemical. A statistical model was employed which tested both for the main effects of chemicals and culture times and for interactions between these factors. Both EMS and BrdUrd significantly affected the percentages of nuclei within the cell-cycle. Exposure to EMS resulted in decreases in the percentages of nuclei in G0 + G1 and increases in the G2 + M compartment. Exposure to BrdUrd affected the size of the G0 + G1 compartment as well as the percentage of S-phase nuclei. Cell growth was reduced as a consequence of increasing EMS concentration and as a function of BrdUrd concentration; the effects of these chemicals were more readily apparent at the later time points. Most importantly, for both the cell-cycle kinetics data and the cell growth data, no evidence of an interaction between the effects of EMS and the effects of BrdUrd was detected statistically. These results may be interpreted to mean that while both EMS and BrdUrd affect the induction of SCE, under the conditions of this experiment, the effects are additive rather than interactive. PMID- 1591625 TI - Limitations of the scrape-loading/dye transfer technique to quantify inhibition of gap junctional intercellular communication. AB - Gap junctional intercellular communication (GJIC) is recognized as playing an important role in normal cell proliferation and development. Chemically induced alteration of GJIC has been proposed to be associated with abnormal cellular growth and/or tumor promotion. Several in vitro assays are currently used to determine the effects of chemicals on GJIC between cultured mammalian cells. One of these assays, the scrape-loading dye transfer (SL/DT) technique, is based on monitoring the transfer of the fluorescent dye Lucifer yellow from one cell into adjacent cells via functional gap junctions. The objective of our study was to evaluate and compare various approaches for quantifying results obtained with the SL/DT technique. Confluent cultures of either WB rat liver epithelial cells or LC 540 rat leydig cells were exposed to the animal tumor promoter 12-O tetradecanoylphorbol-13-acetate (TPA), solvent (0.1% ethanol), or culture medium for one hour at 37 degrees C prior to analysis of GJIC. Inhibition of dye transfer was clearly evident following TPA exposure. Quantification of this dye transfer was assessed via four approaches: manually counting the number of labeled cells; measuring the distance of dye travel from the scrape line; quantifying the amount of cellular dye uptake; and determining the distribution of dye away from the scrape line. Our results suggest that while the SL/DT technique can be effectively used as a tool to determine the qualitative presence or absence of GJIC, its use in quantifying changes in GJIC following chemical exposure is limited. Since concentration-dependent responses are critical in chemical testing, application of the SL/DT method should be restricted to a screening assay for qualitatively assessing the presence or absence of GJIC. PMID- 1591626 TI - [Propofol anesthesia for ophthalmologic surgery in the elderly]. AB - Fifty patients more than 70 years old, ASA I and II, NYHA I and II, were anaesthetized by propofol for cataract or retinal detachment surgery. Induction was carried out by a propofol slow injection (0.5-1 mg.s-1) until loss eyelash reflex (mean dose 0.728 mg.kg-1) and completed by fentanyl 2 micrograms.kg-1 and vecuronium 0.08 mg.kg-1. After intubation, anaesthesia was maintained with nitrous oxide and continued infusion of propofol (mean dose 4.48 mg.kg-1.h-1) according to haemodynamic parameters. These were noted repeatedly and statistically analyzed. No significative differences were observed with younger patients undergoing identical surgical procedures. Haemodynamic effects were the same during cataract or retinal detachment surgery and in hypertensive treated patients vs non hypertensive ones. Recovery was as fast and good as in younger patients. It should be emphasized that propofol doses must be reduced in elderly patients so as to preserve a satisfactory haemodynamic stability. Reasons for increased sensitivity to propofol in elderly patients are briefly discussed. PMID- 1591627 TI - [Peribulbar anesthesia in surgery of the vitreous body and retina]. AB - Peribulbar anaesthesia was used in 40 patients undergoing vitreoretinal surgery; two injections of a mixture of bupivacaine 0.5% and hyaluronidase were performed in the lower and the upper eyelid. Results were judged very satisfactory in 38 of these 40 cases, for anaesthesia as well as for akinesia; no local or systemic complications were observed. Peribulbar anaesthesia is one of the methods of choice, because of its safety; it seems well appropriate for vitreoretinal surgery, provided that its indications are judicious. PMID- 1591628 TI - [The effect of a combination of propofol and fentanyl on cerebral blood flow. A study using transcranial doppler]. AB - The results of the association propofol fentanyl on the velocity of the middle cerebral artery were studied by means of a transcranial doppler on twenty ASA I patients without any intracranial pathology. Anaesthesia induction by propofol (2.5 mg.kg-1) and fentanyl (2 micrograms.kg-1) induced a significant fall of average velocities (p: 0.0001) and an increase of the resistance index (p: 0.0001) without any associated variation of mean blood pressure and CO2 expiratory fraction. These results corroborate the variations of cerebral blood flow and cerebral vascular resistances reported in the literature and give evidence, in all probability, of a cerebral autoregulation phenomenon. PMID- 1591629 TI - [Quality of sedation and neurologic evaluation following surgery of the posterior cranial fossa: the importance of propofol]. AB - Following cerebral posterior fossa surgery, 23 patients were admitted in Intensive Care Unit for postoperative mechanical ventilation. Mean age was 45 +/- 16 years. Mean duration of surgical procedure was 09 h 20 min +/- 04 h 45 min. Heart rate, blood pressure, coma Glasgow scale, pupil reaction, respiratory pattern were recorded throughout the study. Following recovery from anaesthesia sedation was initiated by an intravenous bolus injection of propofol 2 mg.kg-1 followed by a continuous infusion starting at 1 mg.kg-1.h-1. The infusion rate was adjusted thereafter to ensure that the patient was sedated (Glasgow coma scale less than or equal to 6), unable to react to tracheal suction, well adapted to mechanical ventilation with a cardiovascular stability. Mean duration of sedation was 27 h 45 min +/- 04 h 45 min. Mean infusion rate of 3.81 mg.kg-1.h-1 allowed good sedation in 22 patients. There were no clinical changes in arterial pressure and heart rate. Propofol infusion was stopped transiently to assess neurologic status at 18 h +/- 02 h 45, 33 h 45 +/- 08 h 15, 49 h 10 +/- 16 h 50 after sedation onset. During these interruptions, the speed of recovery was assessed and arterial blood samples taken simultaneously. When the infusion was discontinued, adequate recovery was obtained in 48 +/- 26 min for 17 patients of 23, 64 +/- 58 min for 7 of 12, 70 +/- 65 min for 3 of 3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591631 TI - [A conduction problem occurring during anesthesia with propofol combined with fentanyl]. PMID- 1591630 TI - [An analgesic strategy for tympanoplasties]. AB - After induction with vecuronium, etomidate and then isoflurane or enflurane, nitrous oxide, useful at the beginning of tympanoplasty is washed out before the end of operation. So barotrauma on the graft is avoided. In the expectation of analgesia insufficiency, alfentanil is infused intravenously all over the operation period following two modes: constant flow mode (1.25 micrograms.kg 1.min-1) after a bolus (25 micrograms.kg-1): 33 patients; decreasing hyperbolic flow mode (H): cumulative dose = 10.8 x t0.5 (where t = minutes of infusion) = 47 patients. In this mode, plasma concentration is measured by 12 patients. RESULTS: the mean plasmatic level of alfentanil is steady during the 120 minutes duration of anaesthesia: standard deviation is higher than 30%. After high quality anaesthesia in both technics, recovery time was shorter with H mode than with constant flow one (extubation time = 46 +/- 31 min. versus 92 +/- 54 min). H. mode seems to be safer. Though, individual reactivity, drug interaction and genetic polymorphism must make us cautious! Two patients presented apnea 20 and 60 minutes after an efficient awakening. PMID- 1591632 TI - [Severe iatrogenic hyponatremia in a pregnant woman]. AB - Severe hyponatremia may be associated with several complications leading sometimes to the death of the patient. We present the case of a healthy young pregnant woman who developed a severe acute iatrogenic hyponatremia (120 mEq.l 1). The treatment of the acute dehydration due to hyperemesis gravidarum led to a dilutional hyponatremia. The causes, complications and management of severe acute hyponatremia are discussed. PMID- 1591633 TI - [Organ donation: the present situation]. PMID- 1591634 TI - [The 50th anniversary of the introduction of curare in anesthesia]. PMID- 1591635 TI - [The use of buprenorphine for peroperative analgesia]. AB - In an open study, buprenorphine was used as the sole analgesic agent in sixty patients undergoing orthopedic or abdominal surgery. The average dose used was 5 micrograms.kg-1. The level of peroperative analgesia was of good quality and was maintained during the recovery period in the majority of cases. The occurrence of side effects such as nausea, vomiting, respiratory depression was low. PMID- 1591636 TI - Nurses as healers of the spirit. PMID- 1591637 TI - Nursing's role in health care reform. PMID- 1591638 TI - Clindamycin and dry socket. PMID- 1591639 TI - The Inlay Resin method. Accurate crowns under the clasps of partials. PMID- 1591640 TI - Plugging into technology. AB - One of the most important things to consider before buying a computer is use. Where and how will you use your computer? At home (to do household budgeting, some word processing, and play games?), or at the office (to balance complex budgets, calculate payroll, keep a large database of clientele, and possibly have up to 16 users on the system at the same time?). Will you want to integrate your system with imaging, voice response charting and EDI? (The brilliance of EDI alone justifies automation.) Keep in mind that what you do with a computer will probably expand as you get more familiar with the technology, so make sure there's room for growth in the computer you select. Another important aspect to purchasing a computer is service. The company you buy from must be able to provide you with prompt service, and be available when you first explore the realm of microcomputing. If you manage to save money on the purchase price, but it takes six months to have your office computer repaired, you have definitely lost out in the long run. PMID- 1591641 TI - A survival guide for dentists. PMID- 1591642 TI - Infectious or not?--the handpiece controversy. PMID- 1591643 TI - CAD/CAM in dentistry: a historical perspective and view of the future. AB - What can we look forward too? Lots of fun with new CAD/CAM systems that will enhance dentistry, providing quality restorations quickly. The evolution of an array of new versions of already available systems as well as altogether new systems will provide improved quality, expanded capabilities, and increasing user friendliness. And new materials will be more esthetic, wear more nearly like enamel, and strong enough for full crowns and bridges. We can also look forward to lots of change. Because of the cost of CAD/CAM systems, many clinicians are likely to collaborate by sharing a single system. Laboratories and clinicians may collaborate as well, with data being gathered in the operatory and sent to a laboratory via modem. The fabrication would then be done by the laboratory. Other changes that we cannot even predict are likely to occur in dentistry. Exciting times are here. Automation through dental CAD/CAM systems will, most certainly, change the profession. The impact of that change will only be known in the future. But as the future approaches, the systems and materials available to us will continue to evolve, improve, and enhance dentistry. PMID- 1591644 TI - The future of computers in clinical dentistry. AB - It is essential that computer manufacturers and system developers increase their cooperative efforts to establish and maintain standards. Individual, stand-alone systems will not survive, and error-prone integration will prevent progress. File formats--whether graphics or text based--must be completely and seamlessly integrated between users. This has not occurred in other aspects of computer application. Can we expect it to in dentistry? We must. The profession will only reap the true benefits of computerized practice if CDA, ADA, the insurance carriers, manufacturers and developers are willing to sit together and agree to cooperative efforts. Such cooperation is imperative. While initially altruistic, it will be commercially essential in the long run. For many applications, the ability of a computer-based system to quantify information adds a new level to diagnosis. Coupled with this diagnosis support knowledge bases will provide dentists with added sophistication and expanded competence in diagnosis and treatment. It is reasonable to assume that the patient's relevant medical data- medications, status of principal organ systems, etc.--may also be made available electronically. Practice performance data, the legality of entries, and the compilation of and access to national data bases must all respect the patients' and dentists' rights and privacy, while serving society's health care needs. There are some very large issues ahead. Developing the hardware is the easy part.The software is more complex and, as it is specifically designed for dentists, more expensive. The profession is too small to share these costs over the available customer base--limiting the number of vendors that can survive.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591645 TI - Lasers--the new wave in dentistry. PMID- 1591646 TI - Clinical and non-clinical dental sciences: an alliance of necessity. PMID- 1591647 TI - Inflammatory hyperplasias of the oral mucosa. AB - Reactive inflammatory hyperplastic lesions of the oral mucous membranes comprise one of the most common pathological conditions seen in the oral cavity. Over the years, these "lumps and bumps" have been given a wide variety of names and have engendered a spectrum of theories regarding pathogenesis. This article presents a brief overview of these conditions from the perspective of those lesions that are "common" and those that are "not so common." Clinical examples are featured and, while their pathogenesis receives some comment, no attempt has been made to present either an in-depth discussion or a detailed histomorphological description of the various entities. The accompanying bibliography provides sufficient reference material for those wishing more detail regarding reactive hyperplasias of the oral mucosa. PMID- 1591648 TI - [Development of cognitive strategies and self control strategies in 8 to 14-year old children]. AB - This study examines the interaction between the development of cognitive strategies and self-monitoring abilities in children aged 8 to 14. Children were tested individually on eight proportionality problems presented with the balance scale task. Cognitive development was assessed by the strategy used and the performance on each problem. The indicators of self-monitoring were: latencies before and after the solution of a problem, self-evaluation of one's ability to make the balance scale stay level, proportion of oriented moves on the balance scale, and persistence on a problem. Children's self-monitoring reactions to failure were assessed by changes in strategies, verbal explanations, self evaluation of performance, and latencies. Results showed an interaction between the complexity of the items and cognitive level. On more complex items, children of lower cognitive levels had shorter latencies, made more (but less oriented) moves on the balance scale, persisted less in their activity, and had more difficulty to evaluate properly their performance. Following failure, children of lower cognitive levels did a less accurate evaluation of their performance, modified their strategy, and did not change their verbal justification, whereas children of higher cognitive levels did a good evaluation of their performance, did not change their strategy, and had the tendency to change their verbal justification. Following failure, all children took less time planning their activity. The results suggest that self-monitoring abilities develop according to the development of cognitive strategies and are mediated by the complexity of the task. PMID- 1591649 TI - [Selective attention in major depression: clinical retardation and cognitive inhibition]. AB - Relationships between clinical retardation (measured by the Hamilton Depression Inventory) and selective attention (measured with a computerized version of the Stroop word colour test) were studied in a population of 21 depressed patients. Stroop interference was higher in depressed patients than in normals. Desynchronized presentations of the distractor and the target and intervals between responses and succeeding stimuli permitted depressed subjects to respectively apply and lift inhibition of the distractor so that their interference was reduced to control levels. Finally, successive inhibition scores were correlated with the retardation score in depressed subjects. The results are consistent with the hypothesis of a retardation in the application and the lifting of cognitive inhibition in depression. PMID- 1591650 TI - [Transfer of a memorization strategy in 10-year-old children: study of individual differences]. AB - The spontaneous or induced use of an organization strategy is examined on free recall tasks with 10-year-old children classified as rather global or rather analytical at the Group Embedded Figures test. The experimental procedure include three successive and identical tests followed by two deffered tasks, one requiring a transfer of maintenance and the other a transfer of generalization. The experimental group, who attended a simple illustration of the organization strategy before the second test, applied the strategy quickly and successfully: for these subjects, one does not note differences between global or analytical subjects in the recall performance; however, the global subjects modify their study strategy of the material on the generalization task. For the control group, global or analytical subjects have a different evolution for the performance and the strategic attitude according to the procedure. The analytical subjects are different from global subjects on the generalization task. PMID- 1591651 TI - Network interference and number-fact retrieval: evidence from children's alphaplication. AB - The origins of several phenomena of number-fact retrieval were investigated by having children in Grades 3 and 4 memorize alphaplication facts (arithmetic-like memory items composed of letters instead of numbers). Alphaplication performance paralleled memory for arithmetic facts in several important respects: Results showed (a) a large performance advantage for tie (e.g., E, E = j) over nontie problems (E, I = p), (b) that most errors involved answers from the correct alpha table, (c) that response times and error rates were strongly correlated across problems, (d) that the correct answers to poorly learned problems tended to be the most common error responses, and (e) that performance was lower for problems introduced later in the learning sequence. Taken together, these findings support a network-interference approach (Campbell & Graham, 1985) to memory for arithmetic facts. PMID- 1591652 TI - Remote memory: recalling autobiographical and public events from across the lifespan. AB - In this study the recall of autobiographical and public events across the lifespan was examined in a sample of middle-aged and older-aged adults. The tasks were modified versions of one first introduced by Galton (1879), and they required subjects to recall events from specific time periods across their entire lifespan. The four tasks differed in the nature of the episodes requested (autobiographical or public) and whether recall was word-cued or non-word-cued. Verification of public events was assessed archivally, and autobiographical events were verified by a sample of relatives for a subgroup of the subjects and reported events. The results indicated that memory for public events decreases with increased age of the subject, but this effect is not generally found for the recall of autobiographical events. The older-aged subjects were able to recall an equal number of autobiographical episodes from all life segments, whereas recall of news events tended to decrease with remoteness of the episode. These data are contrary to those models that posit general memory loss as a function of age or of remoteness of the events. PMID- 1591653 TI - Reduced endotoxin-induced production of tumor necrosis factor activity by equine peritoneal macrophages exposed to the dual inhibitor of arachidonic acid metabolism, SK & F 86002. AB - The purpose of this study was to determine if a structurally novel dual inhibitor of arachidonic acid metabolism, SK & F 86002, would inhibit the endotoxin-induced production of tumor necrosis factor (TNF) activity by equine peritoneal macrophages. Equine peritoneal macrophages were variously pretreated for 0, 0.5 and 2 h with SK & F 86002 at 10(-9) to 10(-4) molar final concentrations or were left untreated. Then, the macrophages were cultured in vitro in the presence of endotoxin (5 ng/mL). Supernatant media were collected after 4 h and stored at -70 degrees C until assayed for TNF activity and immunoreactive thromboxane B2 (iTxB2). Macrophage supernatant TNF activities were estimated by an in vitro cytotoxicity bioassay using the murine fibrosarcoma cell line, WEHI 164 clone 13. Concentrations of iTxB2 were quantitated by radioimmunoassay. Coincubation of macrophages with SK & F 86002 significantly decreased the subsequent supernatant TNF activity. Concentrations of SK & F 86002 from 10(-7) to 10(-4) molar effectively reduced TNF production when added to macrophages 0 and 0.5 h prior to endotoxin. After 2 h of preincubation, SK & F 86002 significantly reduced supernatant TNF activity at 10(-5) and 10(-4) M concentrations. Supernatant concentrations of iTxB2 were reduced when SK & F 86002 was added at 10(-6) to 10( 4) M concentrations, 0 and 0.5 h prior to endotoxin, and at all concentrations (10(-9) to 10(-4)) when preincubated with macrophages for 2 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591654 TI - Cytological findings in bronchoalveolar lavage fluid from feedlot calves: associations with pulmonary microbial flora. AB - Samples obtained by bronchoalveolar lavage (BAL) were used to evaluate pulmonary cytology in 59 feedlot calves with clinical signs of respiratory disease (cases) and 60 clinically normal comparison calves (controls). Many calves in both case and control groups had inflammatory changes in the lower respiratory tract, as determined by changes in proportions in the BAL differential cell count. Approximately 35% of cases and 40% of controls showed a normal differential cell count. It therefore appeared that the criteria used to select cases for treatment, which were similar to those often used in the field, were poor predictors of lower respiratory tract disease. A positive association was found between an increased proportion of neutrophils in BAL fluid and isolations of Pasteurella multocida and Mycoplasma bovis from BAL fluid. PMID- 1591655 TI - Isolation of pathogenic strains of Haemophilus somnus from the female bovine reproductive tract. AB - The prevalence of Haemophilus somnus in the genital tract of slaughtered and live cows in southern Ontario was investigated. The vagina and uterus of slaughtered cows were swabbed separately. Live cows were examined and sampled in two field surveys: Centre A and Centre B. In the former, aspirated mucus secretions and in the latter, specimens obtained by guarded swabbing were examined bacteriologically. Haemophilus somnus was isolated from 28 genital tracts of 461 slaughtered (6.1%), and seven of 199 live (3.5%) cows during the centre B survey. The isolates were recovered from both normal and diseased reproductive tracts. Fourteen strains isolated from genital organs were examined for pathogenicity in vivo to test the occurrence of pathogenic isolates. In the initial stage of the in vivo study on pathogenicity, each of the fourteen isolates was examined on one calf using an intracisternal inoculation. Subsequently, one pathogenic and one nonpathogenic strain were inoculated into five calves each to statistically confirm their pathogenic potential. Of 14 genital isolates of H. somnus examined in an intracisternal calf assay, six (43%) caused a fatal peracute neurological disease, while eight were nonpathogenic. A comparative pathological study of pathogenic and nonpathogenic isolates showed that the former caused a severe fatal suppurative meningoencephalitis whereas the latter caused no lesions whatsoever or a mild leukocytic leptomeningitis. The salient data obtained in this study indicate that there are pathogenic strains of H. somnus in the genital tract of apparently normal cows as well as of those with inflammatory disease. PMID- 1591656 TI - Studies on efficacy and stability of a vaccine bait containing ERA strain of rabies virus propagated in a BHK-21 cell line. AB - In a dose response study in foxes, the median protective dose of ERA BHK21 vaccine in a blister pack bait was 10(6.0) tissue culture infective doses (TCID)/mL, while artificially aged baits with titers of 10(6.3) TCID/mL induced seroconversion in 78% of foxes. There was no significant difference in the development of antibodies in foxes receiving 1, 2 or 3 mL volumes of vaccine in the bait. When baits were exposed to the elements and fed to foxes over a 21 day period, 85% of the animals seroconverted. Age, sex and the way in which the vaccine container was contacted did not appear to be factors in the responses of these animals. Juvenile foxes, approximately six months of age, were marked more readily with the tetracycline bait marker than older animals. Approximately 25% of foxes did not appear to respond well to vaccination and the titer of the vaccine was a critical factor in producing seroconversion in these animals. PMID- 1591657 TI - Pulmonary immunity in calves following stimulation of the gut-associated lymphatic tissue by bacterial exotoxin. AB - Antibodies in serum and pulmonary lavage fluids were measured in calves following stimulation of the gut-associated lymphatic tissue (GALT) by inoculation of crude leukotoxin of Pasteurella haemolytica into the duodenum through a surgically placed catheter. Nine calves free of P. haemolytica were divided into two groups. Group 1 received an intraduodenal (ID) inoculation of leukotoxin and group 2 received an ID inoculation of phosphate buffered saline. Serum and pulmonary lavage fluids were collected weekly and assayed for antibodies specific to P. haemolytica including immunoglobulin (Ig)G, leukotoxin neutralizing antibodies (LNA), and IgA (lavage fluids only). The multiplicative increase (over baseline) in each class of antibody titer following ID inoculation of leukotoxin, the composite geometric mean increase of all antibodies together, and the composite number of the five antibody titers which increased at least fourfold were computed. Results showed that the geometric mean of each antibody titer and the two composite indices was higher in the GALT-primed groups than in the sham primed group. The differences were statistically significant (p less than 0.05) for serum IgG and for the two composite indices. This experiment demonstrates for the first time that GALT stimulation by bacterial exotoxins results in increased pulmonary antibody levels in calves. PMID- 1591658 TI - Evaluation of conventional and radiometric fecal culture and a commercial DNA probe for diagnosis of Mycobacterium paratuberculosis infections in cattle. AB - Radiometric (RCM) and conventional fecal culture (HEY) and a commercial polymerase chain reaction/DNA probe were evaluated as diagnostic tests for subclinical paratuberculosis in dairy cattle using fecal specimens from a repository of paratuberculosis specimens. The case definition of subclinical bovine paratuberculosis was isolation of Mycobacterium paratuberculosis, by conventional or radiometric culture, from fecal samples or internal organs of dairy cattle without diarrhea or chronic weight loss. Animals designated as free of the disease originated exclusively from certified paratuberculosis-free herds in Wisconsin. Among 182 infected cattle, RCM and HEY fecal culture and the DNA probe had test sensitivities of 54.4%, 45.1% and 33.5%, respectively. Fecal samples from only 111 of the M. paratuberculosis-infected cows tested positive by at least one of the three tests and these cows were designated as fecal shedders; the remaining 71 were considered to have prepatent infections. Among the 111 M. paratuberculosis fecal shedders, RCM, HEY and the probe detected the organism in 89.2%, 73.8% and 55.0% of the fecal specimens, respectively. Herd prevalence significantly affected the sensitivity of all three diagnostic tests (p less than 0.05) but only affected the fecal shedder detection efficiency of the DNA probe (p less than 0.01). No positive DNA probe results were found on 100 randomly selected fecal samples from cows in four certified paratuberculosis-free herds, thus the DNA probe was 100% specific. Probe analyses could be performed in 24 h or less. Time to complete the culture-based tests was 12 wk for HEY and 7 wk for RCM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591659 TI - Morphology and water and lipid contents of stifle menisci of growing swine. AB - Morphology and distribution of water and lipid were examined in menisci of growing swine. The broadness of menisci and the size of protruded tissue in the inner anterior portion of menisci varied among animals. Small tears of tissues were frequently observed. Both the thickness and tissue weight were greater in the lateral than in the medial meniscus. Water content and intensity of glycosaminoglycan staining with safranin-O were found to be greatest in the inner one-third of the meniscus, and greater in the middle than in the outer one-third of the meniscus. Lipid content was greater in the outer one-third than in the inner two-thirds of the meniscus. PMID- 1591660 TI - Lincomycin-induced severe colitis in ponies: association with Clostridium cadaveris. AB - Four groups of two ponies, free of fecal Salmonella and Clostridium cadaveris, were treated as follows: Group A, control group; B, single nasogastrically administered dose of lincomycin (25 mg/kg) followed 48 h later by 3 L of C. cadaveris (10(9) organisms/mL); C, the same dose of lincomycin as group B; D, the same dose of C. cadaveris as group B on each of three occasions at 12 h intervals. Groups A and D remained healthy, but groups B and C developed severe colitis 48-56 h (B) or 72 h (C) after administration of lincomycin. Three ponies were euthanized and one in group B died. Clostridium cadaveris was isolated at about 10(6)/mL of colonic contents from these ponies, but one pony in group B also yielded Salmonella typhimurium from the colon. Subsequent challenge of group A ponies (3 L of C. cadaveris 10(9)/mL, three times at 12 h intervals) did not produce colitis. Nasogastric administration of lincomycin (25 mg/kg) to group A and D ponies, 20 days after administration of C. cadaveris, resulted in severe colitis in all ponies within 48-72 h. Salmonella agona was isolated from the colonic contents of one pony and C. cadaveris (10(6)/mL) from all four ponies. Clostridium cadaveris was not isolated from the colonic content of 45 healthy horses examined immediately after death. These studies confirm the potential for lincomycin to induce severe enterocolitis in ponies and implicate C. cadaveris further as a cause of "idiopathic colitis" in ponies. PMID- 1591661 TI - Nursing sickness in lactating mink (Mustela vison). I. Epidemiological and pathological observations. AB - In a retrospective survey, the epidemiological characteristics of nursing sickness in Standard Black and Pastel mink (Mustela vison) were examined in a Danish fur research farm. Based on the clinical diagnosis of the disease, the overall morbidity in a total of 1774 lactating females amounted to 14.4% and the case fatality rate to 7.8%. Apparently healthy females weaned an average of 5.0 kits per litter, while dams suffering from nursing sickness raised and weaned an average of 5.4 kits per litter (p less than 0.01). Based on logistic regression analysis, the increasing age of the lactating dam, followed by littersize and female weight loss, appeared to be major determinants for the development of nursing sickness. The impact of additional covariates such as litter weight gain and female color type were remarkably low. At weaning (day 43) the mean individual live weight of the kits of either sex did not differ between healthy and sick dams. In Standard Black, the total biomass of the offspring raised by sick dams was significantly larger than that of the healthy controls (p less than 0.01). During the final two weeks of lactation, apparently healthy dams lost on average 14% of their body mass, whereas those affected by nursing sickness had a mean weight loss of about 31% (p less than 0.001). Postmortem examination of 25 dams with severe nursing sickness verified the clinical findings of progressive dehydration and emaciation. The gastrointestinal tract was empty and gastric ulcers and melaena were frequently present. Other common findings included small livers,enlarged adrenals and pitted kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591662 TI - Nursing sickness in lactating mink (Mustela vison). II. Pathophysiology and changes in body fluid composition. AB - An investigation of the pathophysiological characteristics of nursing sickness in mink was carried out as a follow-up study of a previous epidemiological survey at a Danish fur research farm during the 1989 breeding season. In a total of 48 nursing females of the Standard Black and Pastel type, concentrations of several pertinent biochemical constituents of whole blood, plasma, urine and skeletal muscle were determined in order to identify nutritional and metabolic factors involved in the origin and development of the disease. Compared to the reference data obtained in 17 apparently normal lactating dams the findings in 31 females suffering from nursing sickness presented varying clinical and biochemical signs of progressive dehydration and emaciation: aldosteronism, hypovolemia, hyponatremia, hyperkalemia (in the face of muscle potassium depletion), hyperglycemia and azotemic acidemia. Neither ketosis nor severe lactacidemia was observed. The urine was almost devoid of sodium and chloride, and urinary potassium concentration diminished by approximately 50%. The concentrating ability of the kidneys was reduced to less than one third of the maximum value. The results were consistent with severe dehydration and emaciation due to heavy losses of energy, water and body mass along with increasing milk production. The progressive nature of the disease supported the hypothesis that nursing sickness is due to the combined effects of heavy milk production and excessive tissue catabolism along with reduced or ceased dietary intake, and maybe increasing environmental stress. In the advanced stage of the disease coma and death appear to be the inevitable outcome of the metabolic strains for continuing milk production. PMID- 1591663 TI - Familial transmission of speech and language impairment: a preliminary investigation. AB - The familial transmission of speech and language disorders was investigated using a community sample of five year old children with speech and/or language impairment and a control group with normal language skills. The results indicated a significantly higher prevalence rate of language-related problems in families of speech and language impaired children than in normal language controls. Girls with speech/language impairments had more affected relatives than boys, suggesting that girls with this type of family history are at a greater risk of developing speech or language related problems. The pattern of transmission of speech and language disorders was also compared with published reports of the family histories of stuttering and reading disabilities, and with reports of cognitive and linguistic deficits among families of autistic individuals. The findings are discussed in relation to the theory of an underlying neurolinguistic diathesis common to these various disabilities. PMID- 1591664 TI - Psychogeriatric hospitalization: terminable or interminable? AB - This paper takes issue with the stereotype of psychogeriatric patients in the general hospital using beds unnecessarily. With appropriate organization of services involving integrated teamwork, comprehensive patient assessment, early discharge planning and liaison with community resources, a positive outcome and early discharge was achieved with the majority of a group of psychogeriatric patients. PMID- 1591665 TI - Proportion of unmarried siblings of homosexual and non homosexual gender dysphoric patients. AB - Among the siblings of homosexuals, a lack of sexual and romantic interest in women may be independent of erotic feelings for men. This study investigated the sexual histories of siblings of gender-dysphoric outpatients. The patients were classified into three groups: non homosexual males, homosexual males and homosexual females. Their siblings consisted of 301 brothers and 284 sisters over the age of 25. Logistic regression showed that the brothers of the homosexual male patients were significantly less likely to have been married, either legally or common-law, than the brothers of the other gender-dysphoric groups, even with age and relative birth order taken into account. This finding suggests that the low propensity for long term heterosexual relationships seen in homosexual male gender-dysphoric patients also tends to appear in their brothers. PMID- 1591666 TI - When the system is the problem, don't blame the patient: problems inherent in the interdisciplinary inpatient team. AB - Organizational theory used in conjunction with the transference/countertransference paradigm enables members of the interdisciplinary team to look at treatment problems from two perspectives and to intervene at the appropriate level. Common problems of the team are poorly defined accountability, a lack of leadership, communication breakdowns, and boundary violations. Suggested interventions are education of team members about organizational theory, open discussion of contentious issues, and reinforcement of boundaries. The dynamics of the team are important and a team can benefit from self-examination through organizational theory. PMID- 1591667 TI - Bibliotherapy: the use of books in psychiatric treatment. AB - The guided use of selected books as an adjunct to treatment is applicable to patients in all stages of life and with a variety of problems. This paper describes the authors' experience using books as an adjunct to therapy with psychiatric patients. The authors define the term, review the literature, and set out the objectives of bibliotherapy. The paper presents some principles to follow when assigning books, and examples of books used for common problems. Finally, examples are given of bibliotherapy in action at two Ontario hospitals, and some future directions are suggested. PMID- 1591668 TI - A study of competence to consent to treatment in a psychiatric hospital. AB - Sixty patients admitted to an acute treatment ward in a provincial psychiatric hospital were assessed for their competence to consent to psychiatric treatment. A semi-structured interview was used to determine whether they met none, some or all of the four necessary criteria for competence outlined in the Mental Health Act of Ontario. Only 21 of the 60 patients (37%) met all four criteria necessary for a patient to be considered competent to make their own decisions regarding psychiatric treatment. The study outlines the major difficulties in the assessment of competence to consent to psychiatric treatment. Our findings suggest that 74% of patients found incompetent using the current definition in the MHA (Ontario) would fail almost any reasonable test. The implications of these findings are discussed. PMID- 1591669 TI - [Psychosomatic disorder, psychosis and object relations]. AB - This paper presents a case who successively suffered from regional ileitis followed by a reactive psychosis. The author looks at the object relations of a patient afflicted by a narcissistic defect. The fundamental narcissistic disorder models the object relations of the somatic patient and of the psychotic patient. Less differentiation is found in the object representation of the psychotic patient. A comparison is suggested for the two modes of relating to objects. PMID- 1591670 TI - A survey of anxiety disorders clinics in Canadian hospitals. AB - A questionnaire on anxiety disorder services was sent to 240 Canadian hospitals, of which 117 responded. Eighteen of the responding hospitals had anxiety disorder clinics and saw an average of 208 patients a year. These clinics appear to be scarce although, according to epidemiological studies, there is a high prevalence of anxiety disorders in the community. The specific diagnoses of the patients seen in the specialty clinics and the treatments offered generally followed international patterns. PMID- 1591671 TI - Cultural variations in attitudes toward menstruation. AB - Attitudes towards menstruation play an important role in the perception of menstrual distress. The influence of cultural and social factors was studied in a group of 48 Indian women using the Menstrual Attitudes Questionnaire (modified version). Women over 25 years of age were significantly more likely to consider menstruation as being "natural". No other significant relationships were found between menstrual attitudes and demographic variables. The menstrual attitudes of Indian and American college women (from a previous study) were also compared. PMID- 1591672 TI - Planning mental health services: I. Background and key issues. AB - Planning mental health services is a complex task requiring an understanding of background developments and key issues related to mental health services. In Canada, the deinstitutionalization of patients attempted to shift the locus of care from provincial psychiatric hospitals to general hospital psychiatric units. This resulted in the isolation of provincial psychiatric hospitals, general hospital psychiatric units and community mental health programs, with little overall accountability for the services provided--three solitudes. To move toward the creation of responsible, integrated systems a number of issues must be addressed: target population(s); the roles of provincial psychiatric and general hospitals; community support services; continuity of care; co-morbidity; consumerism; and methods of integration. In the development of a comprehensive mental health plan, each issue should be recognized and decisions made which are in keeping with current knowledge. A companion report will survey Canadian initiatives in mental health planning and discuss approaches to many of the issues identified. PMID- 1591673 TI - Contacting the family after a suicide. AB - A two-part survey was conducted on psychiatrists' contact with the families of patients who have committed suicide. Families of suicide victims were surveyed to see if they had been contacted and whether they wished to be contacted. In one of the 12 cases, the psychiatrist initiated a contact, and in 11 of the 12 cases, the families wished they had been contacted. Reasons for the discrepancy between what the psychiatrists did and what the families wanted are discussed. PMID- 1591674 TI - Dangerous offender hearings. PMID- 1591675 TI - Prediction of dangerousness. PMID- 1591676 TI - Alternatives to civil commitment. PMID- 1591677 TI - Preventive detention of the mentally ill. PMID- 1591678 TI - Erotomania in the personals column. PMID- 1591679 TI - Expression of transforming growth factor-alpha in gastric carcinoma and normal gastric mucosa cells. AB - The presence of transforming growth factor-alpha (TGF-alpha) was studied in a total of 120 consecutive patients with gastric carcinomas. This immunohistochemical study found TGF-alpha expression in 60% (n = 72) of carcinomas. It also was detected in normal gastric epithelial mucosa in 36% (n = 43) of specimens. There was no significant statistical correlation between TGF alpha expression and clinical features (e.g., patient age and sex) or pathologic features (e.g., tumor stage, grade, and localization or growth pattern according to an earlier histologic classification). Expression of TGF-alpha by these tumor cells had no influence on prognosis. It was neither a histopathologic marker of high malignancy nor a useful prognostic tool. It had no influence on the invasive growth pattern of gastric carcinoma. PMID- 1591680 TI - Extensive en bloc resection of regionally recurrent carcinoma of the rectum. AB - To remove regionally recurrent cancer of the rectum completely, more radical extensive resections were attempted than the conventional ones in 35 patients. Twenty-two patients underwent total pelvic exenteration. In 23, sacral resection was done, combined with other procedures including excision of the entire circumference of the lower pelvic ring. There were two hospital deaths. Delayed wound healing was seen in ten. Preoperative severe pain was alleviated in 18. Also, perineal ulcer, vaginal bleeding, bloody stools, and tenesmus disappeared. Of the four 5-year survivors (estimated rate, 23%), only one was disease-free. A second recurrence was seen in 27 patients, of whom 23 had regional failure. It was concluded that so-called local recurrence is a lesion more widespread than indicated by imaging and biopsy. Therefore, even the most radical resection rarely can cure this disease. However, such a surgical procedure can afford more effective palliation than other treatments and may prolong life in selected patients significantly. PMID- 1591681 TI - Peaks in plasma plasminogen activator inhibitor-1 concentration may explain thrombotic events in cases of pancreatic carcinoma. AB - Pancreatic carcinoma is associated with a high frequency of thrombosis. Most patients with thrombotic disease have a defective fibrinolytic defense system caused either by plasminogen activator deficiency, excess of plasminogen activator inhibitor (PAI-1), or a combination of the two. In the current series of 27 patients with pancreatic carcinoma, 17 had had deep vein thrombosis (DVT) since the onset of their malignant disease, and most were found to have high plasma concentrations of PAI-1 antigen and PAI-1 activity. Analysis of singleton samples from each patient yielded no correlation between previous DVT and currently high plasma PAI-1 concentrations. However, serial samples from 14 patients (8 of whom had histories of thrombosis) showed individual values varied sharply with time, with intermittent peaks both in PAI-1 antigen and PAI-1 activity for 11 of the 14 patients. Such variability may contribute to intermittently excessive hypercoagulability because of a relative reduction in fibrinolytic potential. These changes may predispose the patient to have thrombotic events in association with pancreatic carcinoma. PMID- 1591682 TI - Pulmonary surfactant protein A in pleural effusions. AB - Pulmonary surfactant protein A (SP-A) is known to be a major phospholipid associated glycoprotein in pulmonary surfactant, which is specific to the lung. Immunohistochemically, expression of SP-A in tumor tissues is found in approximately 50% of patients with lung adenocarcinoma but not in the other histologic types of lung cancer of metastatic lung tumors. In this study, the SP A content of pleural effusions was determined using an enzyme-linked immunosorbent assay. These results showed that approximately 40% of patients with lung adenocarcinomas (27 of 67) had high levels of SP-A (greater than 500 ng/ml) in their pleural effusions. By contrast, patients with other histologic types of lung cancers, adenocarcinomas of different primary sites, and tuberculosis had low levels of SP-A in their pleural effusions. The determination of SP-A in malignant effusions will contribute to distinguishing primary lung adenocarcinoma from adenocarcinomas of miscellaneous origin. PMID- 1591683 TI - Large cell lymphoma of the mediastinum with marked tropism for germinal centers. AB - The cases are presented of three patients with large cell malignant lymphoma of the mediastinum with a distinctive growth pattern characterized by marked tropism of tumor cells for germinal centers. The patients' ages ranged from 35 to 70 years; one was a woman, and two were men. Histologically, the lesions were characterized by a proliferation of large atypical cells arranged in clusters that encroached on mantle zones and invaded germinal centers. Immunohistochemical studies showed positive staining of the tumor cells for leukocyte common antigen, L-26 (pan-B-cell antigen), and lambda light chain restriction and negative staining with Leu-M1, UCHL-1 (pan-T-cell antigen), Ber-H2 (Ki-1 antigen), S-100 protein, HMB-45, low-molecular weight keratins, epithelial membrane antigen, carcinoembryonic antigen, and placental alkaline phosphatase. Electron microscopy done on one specimen showed cells with abundant cytoplasm, some of them containing surface microvilli, scant organelles, and scattered polyribosomes consistent with lymphoid cells. Because of their unusual growth pattern and morphology, these tumors can be mistaken for primary or metastatic carcinomas, germ cell tumors (particularly seminomas), and metastatic malignant melanomas. It is proposed that the "germinotropic" features observed in these lesions are the result of active colonization of germinal centers by the tumor cells. The possible pathogenetic implications of this phenomenon are discussed. PMID- 1591684 TI - Meningioma of the mandible. AB - This is the first case report to the authors' knowledge of a primary extracranial meningioma located in the mandible. Ultrastructurally, the tumor cells had intricate cellular membranes and desmosome-like attachment structures. Using immunohistochemical analysis, the tumor expressed both epithelial membrane antigen and vimentin. Although the origin of extracranial meningiomas has been attributed to proliferation of ectopic embryonal nests of arachnoidal cells, the proliferation of perineural cells of peripheral nerves also is possible as a result of the structural and functional similarities of perineural cell and arachnoid cells. The authors suggest that extracranial meningiomas may be more common than published reports indicate because of certain histologic similarities between these tumors, neurilemomas, and solitary neurofibromas. PMID- 1591685 TI - Aneurysmal bone cyst. A clinicopathologic study of 238 cases. AB - Aneurysmal bone cyst (ABC) is a nonneoplastic expansile bone lesion that mainly affects children and young adults. Primary ABC is relatively rare, with an incidence one half that of giant cell tumor of bone. In 238 patients with ABC studied in the Mayo Clinic files, more than 80% of the lesions were in long bones, flat bones, or the spinal column. Of the lesions initially treated at the Mayo Clinic, 95% were typical ABC; the rest were "solid" variants. Except for the absence of obvious cavernous channels and spaces, there was no significant histologic difference between solid variant and typical ABC. Radiographically, ABC is an eccentric expansile lesion commonly located at the metaphysis of long bones. Computed tomography and magnetic resonance imaging may show multiple internal septations or fluid levels. In the 153 patients treated, 19% had recurrence after curettage (intralesional excision). Recurrence was most common during the first 2 postoperative years. PMID- 1591686 TI - Ultrasonically guided percutaneous splenic tissue core biopsy in patients with malignant lymphomas. AB - Ultrasonically (US) guided percutaneous tissue core biopsy of the spleen was done on 46 patients with malignant lymphomas. The biopsies were undertaken as a staging procedure in 32 patients, as a restaging procedure in 7, during follow-up in 2, and as a diagnostic step in 5 (previously undiagnosed cases with clinically and ultrasonographically suspected lymphoma). In 45 patients, the tissue core specimens obtained by US-guided biopsies were sufficient for a correct histologic examination; in one patient, the specimen was considered inadequate. The tissue core specimens showed splenic involvement in 12 patients and normal splenic tissue in the other 33. These latter cases were confirmed by splenectomy, by laparoscopy with larger splenic biopsy needles, and by clinical and US follow-up over a period of 6 to 30 months. In all previously undiagnosed patients (five), splenic biopsies allowed histologic subtyping. Additional immunologic subclassification into B-cell and T-cell types of lymphomas was done in two instances. There were no complications in this series. These results suggest that percutaneous US-guided splenic tissue core biopsy is a useful and safe technique for the diagnosis, staging, and follow-up of malignant lymphoma. PMID- 1591687 TI - Nucleolar organizer region enumeration in keratoacanthomas and squamous cell carcinomas of the skin. AB - Keratoacanthomas (KA) and squamous cell carcinomas (SSC) are epithelial skin tumors exhibiting distinctive clinical and histologic features. However, the differential diagnosis between them in individual cases may be difficult or even impossible. In this article the authors examine the possibility that enumeration of associated proteins of nucleolar organizer regions (AgNOR) could be of help in differentiating KA from SCC. AgNOR counting, performed on unequivocal cases of SCC (n = 20) and KA (n = 16) showed statistically significant higher AgNOR counts in SCC (6.29 +/- 0.91) compared with KA (3.80 +/- 1.62). This result speaks in favor of the different biologic nature of SCC and KA; however, due to significant overlap between the two groups, AgNOR enumeration alone is not sufficiently discriminating so as to be used diagnostically in cases with borderline histologic features. PMID- 1591688 TI - Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations. AB - Balloon cell malignant melanoma (BCMM) is a rare histologic variant of malignant melanoma (MM). Thirty-four patients with BCMM from the files of the Armed Forces Institute of Pathology (AFIP) were studied by means of clinicopathologic correlation and histochemical, immunohistochemical, and ultrastructural methods to better define this entity. The cytoplasmic features of the balloon cells observed in BCMM resemble those noticed in balloon cell nevus (BCN), but the presence of nuclear pleomorphism, atypia, and mitoses and the absence of intervening stroma help distinguish BCMM. The cells also show many histochemical, immunochemical, and ultrastructural features of conventional melanoma cells. Although it is generally believed that balloon melanoma cells represent a degenerative change, the immunohistochemical and electron microscopic findings suggest that the balloon tumor cells are most likely metabolically active melanocytic cells. Microscopically, BCMM also must be differentiated from other clear cell tumors such as clear cell sarcoma (MM of soft parts), hibernoma, xanthoma, sebaceous neoplasms, metastatic renal cell carcinoma, (malignant) clear cell acrospiroma, (malignant) granular cell tumor, granular (clear) cell basal cell carcinoma, clear cell syringoma, and atypical fibroxanthoma. The prognosis of BCMM usually correlates with the tumor thickness similar to that in other histologic types of cutaneous MM. Nineteen (57.5%) of 33 patients with adequate follow-up information died of disseminated tumors from 2 months to 12 years after the initial treatment. Six (18.2%) patients developed local recurrences: four of these patients died of metastasis and two were alive with metastatic tumor at last contact. Five (15.2%) patients were alive with metastatic tumors, and seven (21.2%) were alive without evidence of disease at last contact. Recognition of BCMM is important because of its malignant biologic behavior. PMID- 1591689 TI - Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients. AB - The current study has prospectively investigated the incidence and course of ocular toxicity after low-dose tamoxifen treatment. Sixty-three patients with cancer who could be examined were analyzed. Tamoxifen was administered on a 20-mg daily dose. Median duration of treatment was 25 months. Median total tamoxifen dose was 14.4 gr. Four patients had retinopathy and/or keratopathy 10, 27, 31, and 35 months, respectively, after tamoxifen initiation (an incidence of 6.3%). Ophthalmologic findings consisted of decreased visual acuity, bilateral macular edema, yellow-white dots in the paramacular and fovea areas in all patients as well as corneal opacities in one patient. After tamoxifen withdrawal almost all ocular abnormalities were found to be reversible, except for the retinal opacities. This is the first prospective study in the literature indicating that even conventional low-dose tamoxifen treatment can induce ocular toxicity. In addition, the authors review and discuss the literature of the last decades. PMID- 1591690 TI - Poor prognosis associated with thrombocytosis in patients with cervical cancer. AB - The medical records of 113 patients treated with radiation therapy for invasive cervical cancer between 1975 and 1985 were retrospectively reviewed. Patients with thrombocytosis (platelet count greater than 400,000/microliters) were compared with those with normal platelet counts. Thrombocytosis was present at the initiation of therapy in 20 (17.7%) of the 113 patients. The 5-year cumulative survival rate for the 93 patients with normal platelet counts was 65%, whereas it was 25% for the 20 with thrombocytosis (P less than 0.0001, log-rank test). Using Cox's proportional hazards model, thrombocytosis continued to correlate strongly with poor survival even when adjusted for histologic type, patient age, and disease stage (P less than 0.001). Thrombocytosis is an independent indicator of poor prognosis in patients with cervical cancer. PMID- 1591691 TI - The role of fine-needle aspiration biopsy of the prostate in staging adenocarcinoma. AB - Stage A prostate cancer is defined as the incidental finding of cancer in specimens obtained by transurethral resection of the prostate (TURP) in a clinically benign gland. A low-to-moderate grade tumor involving less than 5% of the TURP specimen has been termed Stage A1; a high-grade tumor or tumor involving more than 5% of the TURP specimen is termed Stage A2. Most investigators agree that Stage A1 disease has a significantly better prognosis than Stage A2 disease and may not warrant radical prostatectomy. However, the problem of correctly differentiating A1 and A2 disease remains. The authors prospectively studied 100 consecutive patients undergoing TURP for outlet obstruction without clinical suspicion of prostate cancer by digital examination. Each patient underwent fine needle aspiration biopsy (FNAB) of each side of the prostate immediately before TURP. These data show that the addition of preprostatectomy FNAB increased the incidence of finding adenocarcinoma of the prostate from 10% to 14%. An additional 3% had FNAB results that were highly suspicious. A positive correlation between cytologic and histologic findings was seen in 83% of patients. Of three patients with Stage A2 prostate cancer, none had malignant cytologic findings. Of seven patients with Stage A1 disease, five (71%) had suspicious or malignant cytologic findings. Seven patients (7%) had suspicious or malignant cytologic findings with no histologic evidence of tumor. In conclusion, preprostatectomy FNAB cannot differentiate Stage A1 from Stage A2 prostate cancer. However, the procedure does increase the yield of finding incidental prostate cancer. The therapy of patients with either (1) malignant cytologic findings alone (Stage A0 disease), or (2) Stage A1 histologic and malignant cytologic findings (Stage A1+) is unclear at present. PMID- 1591692 TI - Significance of a new stratification of alkaline phosphatase and extent of disease in patients with prostate carcinoma with bone metastasis. AB - Bone is the most frequent site of metastatic prostate cancer and the prognosis of patients with bone metastasis is poor. The authors have investigated a semiquantitative system to evaluate bone metastatic lesions in terms of cancer specific survival. Based on the extension of disease (EOD) grade proposed by Soloway and associates, a new EOD grading system obtained from bone scintigraphy alone and EOD score obtained from bone scintigraphy and alkaline phosphatase was studied in 164 patients with prostate cancer with metastatic bone involvement. In terms of a cancer-specific survival and prostate cancer death, both the new EOD grade and the EOD score were apparently superior to eight other items studied (age, medical score, gait disturbance, histologic grade, erythrocyte sedimentation rate, prostatic acid phosphatase, and alkaline phosphatase). Multivariate analysis revealed that the EOD score was better than the new EOD grade. This improvement was due to the elimination of false-positive or nonactive metastatic bone lesions on bone scintigraphy through the alkaline phosphatase evaluation. PMID- 1591693 TI - The streptococcal preparation OK-432 specifically augments the susceptibility of human urinary bladder tumor cells to autologous peripheral blood lymphocytes. AB - The streptococcal preparation OK-432 was tested for its ability to enhance the susceptibility of fresh urinary bladder tumor (UBT) cells to autologous peripheral blood lymphocytes (PBL) in patients with UBT. PBL treated with OK-432 at 0.1 Klinishe Einheit (KE)/ml for 18 hours killed the human T24-lined UBT cells and freshly separated autologous UBT cells more efficiently than untreated PBL. Treatment of K562 erythroleukemia cells with OK-432 at 0.1 KE/ml for 18 hours had no effect on their susceptibility to lysis by fresh PBL. In contrast, treatment of T24 and fresh autologous UBT cells with OK-432 resulted in an enhancement of their susceptibility to PBL. The susceptibility of autologous UBT cells to both large granular lymphocytes (LGL) and T-lymphocytes was also enhanced by treatment of tumor cells with OK-432. Binding of PBL to T24 and fresh autologous UBT cells was also augmented by treatment of the tumor cells with OK-432. The frequency of binding of OK-432 to fresh UBT cells was positively correlated with the increased target sensitivity to autologous PBL. The inhibition of RNA synthesis in fresh UBT cells by OK-432 was also associated with the elevated susceptibility to autologous PBL. These results indicate that OK-432 activates the autologous tumor killing system through stimulation of effector cells and elevation of target susceptibility to effector cells in patients with UBT, and suggest that the OK 432-augmented target sensitivity to PBL may be oriented specifically to UBT cells and local immunotherapy with OK-432 may be remarkably beneficial in the treatment of UBT. PMID- 1591694 TI - A study of metastatic cancer found during inguinal hernia repair. AB - Among 22,816 inguinal hernia repairs done between 1950 and 1988, 15 patients (0.07%) had metastatic tumors found within their hernias. Inguinal herniation was the initial sign of cancer in six patients. A palpable inguinal mass (53%) and abdominal or groin pain (67%) were the most common presenting sign and symptom, respectively. Primary tumor sites included the gastrointestinal tract (40%), ovary (20%), prostate (13%), mesothelium (13%), and unknown sites (13%). The median patient survival was 20 months and depended on the primary tumor site. Grossly apparent inguinal hernia sac abnormalities should be examined microscopically to avoid missing the diagnosis of metastatic cancer, but routine histologic examination of all hernia sacs is not warranted. PMID- 1591695 TI - Combination chemotherapy with ifosfamide and etoposide is effective in the treatment of central nervous system metastasis of childhood neuroblastoma. AB - Childhood neuroblastoma is a neural crest-derived tumor that presents most commonly during this period of life. In disseminated form, it is resistant to cure by chemotherapy. The tumor tends to recur in diverse locations after an initial clinical response. The parenchyma of the central nervous system (CNS) is a rare location for metastatic disease and typically represents terminal disease spread. Therefore, effective therapy for CNS metastasis of neuroblastoma has not been reported. The authors describe the case of a child who had a large parenchymal CNS metastasis at the time of initial recurrence of Stage IV neuroblastoma. Chemotherapy with ifosfamide and etoposide resulted in complete resolution of this lesion. PMID- 1591696 TI - Cisplatin-based chemotherapy in a renal transplant recipient. PMID- 1591697 TI - Postoperative radiation therapy for rectal cancer: an interim analysis of a prospective, randomized multicenter trial in The Netherlands. PMID- 1591698 TI - Postoperative radiation therapy for rectal cancer: an interim analysis of a prospective, randomized multicenter trial in The Netherlands. PMID- 1591699 TI - A simple method of chromosomal analysis for malignant solid tumors. PMID- 1591700 TI - bcr breakpoint location in Spanish patients with chronic myelogenous leukemia. PMID- 1591701 TI - A multidrug-resistant ovarian carcinoma cell line with a malignant suppressed phenotype is a CD44 gene expression defective mutant. AB - A multidrug-resistant cell subline (OV1/VCR) derived from an ovarian adenocarcinoma cell line (OV1/P) was characterized by a typical suppressed malignant phenotype and by a unique karyotypic change: del(11)(p13). In an attempt to discern some genetic alteration of 11p genes that may be relevant to the phenotypic shift, cells were analyzed with DNA probes mapped in the deleted region and with monoclonal antibodies (MoAbs) against 11p-encoded membrane molecules. Southern blot did not detect abnormal restriction patterns of the probed sequences. OV1/VCR cells did not express the CD44 epitope (11p13 MIC4 locus) recognized by the F10-44 MoAb and did not accumulate RNAs of the CD44 (Hermes) core peptide. This defect was not detected in another OV1/P-derived drug resistant subline that retained the malignant behavior and did not have the del(11p) marker. It may have contributed to phenotypic reversion because evidence shows that CD44 membrane molecule is involved in cell-cell interaction and growth regulation of cancer cells. PMID- 1591702 TI - Aberrations of chromosome 19. Do they characterize a subtype of benign thyroid adenomas? AB - We describe the cytogenetic findings in two benign thyroid hyperplasias with aberrations of chromosome 19. In the first patient, two of four nodules showed identical translocations involving chromosome 19 and 22: 46,XX,der(19)t(19;?)(q13;?),der(22)t(22;?)(q12;?), the remaining nodules had an apparently normal karyotype. Two nodules from a second patient were karyotyped. One showed a karyotype 46,XX,t(1;19)(p35-36.1;q13) and the other had a normal karyotype. From these results as well as those reported previously, we can conclude that structural changes of chromosome 19 characterize a subgroup of thyroid adenomas, thyroid hyperplasias, or both. PMID- 1591703 TI - Trisomy 2 in proliferative fasciitis. AB - We report trisomy 2 as the sole clonal karyotypic abnormality in a case of proliferative fasciitis. To our knowledge, this is the first cytogenetic report of proliferative fasciitis. PMID- 1591704 TI - Chromosome rearrangements at 12q13 in two cases of chondrosarcomas. AB - We analyzed the karyotypes of two moderately differentiated (grade 2) chondrosarcomas. Case 1 had a reciprocal translocation between chromosomes 6 and 12, t(6;12)(q25;q13) in most of the cells analyzed, as well as trisomies of chromosomes 7, 8, 11, 17, 19, and 21 and tetrasomy of chromosome 19. A reciprocal translocation involving chromosomes 12 and 19, t(12;19)(q13;q13), was noted as a highly clonal abnormality in the other case. Some cells had t(12;19) as the sole chromosome abnormality. Thus, chromosome rearrangements involving the long arm of chromosome 12 at the same region (q13) were commonly identified in the two tumors. These findings suggest that the rearrangements at 12q13 are nonrandom acquired changes that characterize a subgroup of chondrosarcomas. PMID- 1591705 TI - Translocation (6;16) in a case of granulosa cell tumor of the ovary. AB - We performed a cytogenetic study of an ovarian granulosa cell tumor (GCT). Tumor cells showed a translocation (6;16); the full karyotype was 45,XX 6,dic(6;16)(q11;q22)/44,XX,-6,-22,dic(6;16)(q11;q22),-22/46,XX,- 6,dic(6;16)(q11;q22), +dic(6;16)(q11;q22). This is the second case of GCT with structural changes of chromosome 6 leading to loss of 6q material. PMID- 1591706 TI - Cytogenetic changes in hepatocarcinomas from rats treated with chronic exposure to diethylnitrosamine. AB - Cytogenetic analysis of rat hepatocarcinomas obtained after diethylnitrosamine (DEN) exposure showed a wide variety of numerical and structural chromosomal changes: 53 of 86 hepatocellular carcinomas showed at least one recurrent chromosomal aberration. Some of these recurrent changes occurred in several tumors. Chromosomes 1, 3, 11, and 12 were abnormal in more than 30% of the carcinomas; chromosomes 2, 4, 5, and 10 were abnormal in 10%. Moreover, chromosomes 1 and 10 were generally lost or deleted and chromosome 3, 4, and 11 were very often gained. The most frequent anomaly was loss of chromosome 1 which was observed in 35% of the tetraploid cell populations. The occurrence in several tumors of recurrent chromosomal rearrangements as well as various repeated aneuploidies strongly suggests that these anomalies are implicated in the process of rat hepatocarcinogenesis induced by DEN treatment. PMID- 1591707 TI - Survival of patients with t(1;7)(p11;p11). Report of two cases and review of the literature. AB - t(1;7)(p11;p11) is a relatively rare chromosome aberration, in most cases associated with acute myeloid leukemia or myelodysplasia. Earlier, many patients received chemotherapy for a malignant disease. The prognosis is usually poor. I describe two patients and review the literature. Thirty-six of the 73 had a history of previous exposure to chemotherapy or radiotherapy. Alkylating agents had been used in 29. The median survival after observation of the translocation was only 11 months, a much shorter survival time than is common for patients with secondary hematologic disorders. Sex, diagnosis, hemoglobin concentration, and percentage of metaphases containing t(1;7) were independent prognostic factors. Despite its relation to earlier chemotherapy, the chromosome aberrations associated with t(1;7) lack the cytogenetic features characteristic of therapy induced disorders. PMID- 1591708 TI - Uterine stromal sarcoma cell line. A cytogenetic and electron microscopic study. AB - Uterine sarcomas constitute approximately 3% of all malignant uterine corpus tumors. Of these, the tumors that originate solely in the stromal elements of the uterine wall are relatively infrequent and have not been well characterized cytogenetically. We report data from a low-grade endometrial stromal sarcoma both at the time of resection and after months in long-term tissue culture. Cytogenetic analysis showed a clonal population of cells with an abnormal karyotype of 46,XX,del(5)(q31.1),der(7)t(6;7)(p21;p22) which remained unchanged in long-term culture. Electron microscopy suggests that these cells are similar to other neoplastic cells in having immature-appearing nuclei surrounded by a relatively mature cytoplasm (with well-developed organelles). Determination of the specificity of these observations must await study of additional stromal sarcomas. PMID- 1591709 TI - Chromosome abnormalities in low-grade central nervous system tumors. AB - Ependymomas, oligodendrogliomas, and low-grade astrocytomas are slow-growing central nervous system (CNS) tumors that occur in both adults and children, whereas craniopharyngiomas and choroid plexus papillomas occur predominantly in children. We examined karyotypes of 32 of these low-grade tumors, including ten oligodendrogliomas, six ependymomas, 11 low-grade astrocytomas, four craniopharyngiomas, and one choroid plexus papilloma. Only normal karyotypes were obtained from 6 oligodendrogliomas. The rest had normal stemlines; three tumors had 45,X,-Y sidelines and one tumor had a sideline of monosomy 22. The most frequent abnormalities in the ependymomas were +7 (three tumors), -21 (two tumors), -22 (two tumors), and del(9)(p22) (two tumors). Gains of chromosome 7 and deletions of 9p were found more often in high-grade gliomas. Seven low-grade astrocytomas had normal stemlines, two had chromosome 7 abnormalities, a pilocystic astrocytoma had +der(15), and one tumor had a -Y sideline. The four craniopharyngiomas and one choroid plexus tumor were all apparently normal. The cytogenetics of low-grade CNS tumors differ from higher grade gliomas in that most low-grade tumors show little deviation from the normal karyotype. PMID- 1591710 TI - Comparison of DNA and karyotype ploidy in malignant mesothelioma. AB - The correlation between flow cytometric analysis and classical karyotyping was examined in malignant mesothelioma. Flow cytometry was used to determine the DNA ploidy mainly from paraffin blocks of 31 mesotheliomas, of which the S-phase fraction (SPF) could be defined in 17 tumors. Chromosomal results were available from 27 of these tumors. For the comparisons, both the modal (the most common) and the mean (the average) chromosome numbers were determined. A significant correlation was observed between ploidy pattern, i.e., DNA indexes and modal as well as mean chromosome numbers (p = 0.004 and p = 0.006, respectively). Otherwise the comparison between the mean chromosome numbers and DNA index proved more relevant. Although the majority of the tumors (16 of 27) had a normal modal chromosome number of 46, only 5 tumors had a normal mean chromosome number, and the remaining 22 had an abnormal number, reflecting the divergent chromosomal abnormalities. Furthermore, comparison of SPF with mean chromosome numbers disclosed a parabolic relationship; i.e., when mean chromosome number corresponded to diploid, near-diploid, or near-tetraploid cell, SPF was low, but SPF was at the maximum when mean chromosome number ranged between 60 and 63. Because SPF is an indicator of cell proliferation, this might suggest that the number of chromosomes as such also corresponds with the growth characteristics of malignant mesothelioma. PMID- 1591711 TI - Cytogenetic damage in peripheral blood lymphocytes of cancer patients prior to radiotherapy. AB - In a study comprised of 79 cancer patients selected for determining chromosomal damage to peripheral blood lymphocytes before, during, and after radiotherapy, four patients revealed chromosome aberrations prior to radiotherapy in 5% of the cells examined. The most common anomalies were dicentric chromosomes and translocations of unidentified chromosomal material on the long or short arm. We attribute this high incidence of chromosomal aberrations before radiotherapy to a combination of various external factors that are known to cause such cytogenetic injury. PMID- 1591712 TI - Chromosome instability before cancer therapy. PMID- 1591713 TI - New case of t(3;17)(q26;q22) as an additional change in a Philadelphia-positive chronic myelogenous leukemia in acceleration. AB - A new case of t(3;17)(q26;q22) was observed in a Philadelphia-positive (Ph+) chronic myelogenous leukemia in acceleration 1 month before occurrence of the blastic phase. Abnormal megakaryocytopoiesis and thrombopenia were noted, but blast cells did not express platelet markers. The same translocation was previously reported in three myeloproliferative disorders in acceleration or in the process of becoming acute. Translocations or inversions of chromosome 3 with breakpoint involving the band 3q26 were specifically associated with megakaryoblastic acute phase or abnormal megakaryocytopoiesis. This report confirms that the t(3;17)(q26;q22) is a specific nonrandom chromosomal abnormality associated with the acute nonlymphoblastic phase of myeloproliferative disorders and megakaryocytopoiesis dysfunction. PMID- 1591714 TI - Unbalanced 6p translocation as primary karyotypic anomaly in secondary acute nonlymphocytic leukemia. AB - A case of acute nonlymphocytic leukemia after radiochemotherapy for Hodgkin's disease, with a rearrangement of 6p23 region, is described. This chromosome change, which has been previously reported in secondary leukemias or myelodysplastic syndromes, was an isolated karyotypic anomaly in our case, which strongly supports the nonrandom involvement of chromosome 6p in induced leukemias. PMID- 1591715 TI - Karyotypic and clinical progression in chronic myelogenous leukemia after 30 years. PMID- 1591716 TI - Involvement of 19q13 in follicular thyroid adenoma. AB - Cytogenetic investigation of a follicular thyroid adenoma from a 31-year-old woman showed a t(16;19)(q12;q13), as the sole chromosome abnormality. As five more cases with 19q13 involvement have been described, we suggest that the terminal region of the long arm of chromosome 19 is important for the development of follicular thyroid adenoma. PMID- 1591717 TI - Polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose in combination with interleukin 2 in patients with cancer: clinical and immunological effects. AB - We have performed a phase IB study of polyinosinic-polycytidylic acid complexed with poly-L-lysine and carboxymethylcellulose (poly-ICLC) in combination with interleukin 2 (IL-2) in 25 patients with a variety of cancers. Patients received weekly or biweekly poly-ICLC by i.m. injection, at doses ranging from 0.01 to 1.0 mg/m2, for 1 month. This was followed by 2 months of outpatient therapy with biweekly i.m. poly-ICLC in combination with IL-2 (3 x 10(6) units/m2) given i.v. by 24-h continuous infusion twice weekly, using a portable infusion pump. No objective tumor responses were observed. Toxicity was moderate at all poly-ICLC doses tested and increased only slightly following the addition of IL-2. No increases in peripheral blood natural killer (NK) activity were observed after treatment with poly-ICLC alone. However, high dose poly-ICLC (greater than or equal to 0.3 mg/m2) in combination with IL-2 resulted in NK activity greater than that seen using the same dose of IL-2 in combination with lower poly-ICLC doses. Increases in the number and percentage of CD56+ cells were evident only after initiation of IL-2 therapy and were unaffected by the poly-ICLC dose. In the majority of patients, these increases were preferentially associated with the subset of CD56+ cells coexpressing CD8, while the CD56+/CD16+ population was elevated to a lesser extent. Moderate increases in serum neopterin levels and 2',5'-oligoadenylate synthetase activity in peripheral blood mononuclear cells were noted at 72 h following initial treatment with 1.0 mg/m2 poly-ICLC. No induction of alpha or gamma interferon was detected. This study shows that the addition of poly-ICLC to a well tolerated IL-2 regimen can significantly enhance NK activity. Poly-ICLC can be used to enhance IL-2-induced NK lytic activity without increases in the dose and, therefore, the toxicity of IL-2 treatment. PMID- 1591718 TI - The antitumor effects of the quinoline-3-carboxamide linomide on Dunning R-3327 rat prostatic cancers. AB - Linomide (N-phenylmethyl-1,2-dihydro-4-hydroxyl-1-methyl-2-oxo-quinoline-3- carboxamide) is a quinoline 3-carboxamide which previously has been demonstrated to produce immunomodulator and antitumor effects when given in vivo. To test the possible antitumor effects of linomide against prostatic cancers, rats bearing five distinct Dunning R-3327 rat prostatic cancer sublines were treated daily with i.p. injections of linomide. These studies demonstrated that linomide has a reproducible antitumor effect against all of the prostatic cancers tested regardless of their growth rate, degree of morphologic differentiation, metastatic ability, or androgen responsiveness. This antitumor effect is observed only in vivo, not in vitro, and involves a cytotoxic response of the prostatic cancer cells. This cytotoxic response results in the retardation of the growth rate (i.e., increased tumor volume doubling time) of primary prostatic cancers and in metastatic lesions. Linomide's growth retardation is reversible, and thus continuous daily treatment with linomide is required for maximal antitumor response. Pretreatment of rats with linomide before tumor inoculation has no effect in addition to that produced by initiating linomide treatment at the time of tumor inoculation. No enhancement of either natural killer cell number or natural killer cell cytotoxic activity is induced by linomide treatment in the tumor-bearing rats. In addition, depletion of natural killer cell activity via injections of asialo-GM1 antiserum does not prevent the antitumor effects of linomide in vivo. Likewise, the antitumor effects of linomide are also produced in prostatic cancer-bearing athymic nude rats. These results suggest that the requirement for host involvement in the antitumor effects of linomide against rat prostatic cancers may involve both immune and nonimmune host mechanism(s) (e.g., antiangiogenesis). PMID- 1591719 TI - Comparative metabolism in vitro of a novel carcinogenic polycyclic aromatic hydrocarbon, 1,2,3,4-tetrahydro-7,12-dimethylbenz[a]anthracene, and its two regioisomeric B-ring fluoro analogues. AB - A novel biotransformation pathway likely exists for carcinogenic 1,2,3,4 tetrahydro-7,12-dimethylbenz[a]anthracene (THDMBA), since this A-ring-reduced polycyclic aromatic hydrocarbon does not have an aromatic bay-region. The comparative metabolism of THDMBA, a non-carcinogenic 5F analogue, and a more carcinogenic 6F-THDMBA species was examined to determine potential DNA-bonding metabolites. Rat liver microsomes from phenobarbital-treated animals were incubated in the presence of THDMBA (or fluoro-THDMBA), NADPH, and O2. Metabolic products and the parent compound were extracted into organic solvent and analyzed/purified using reversed-phase high-performance liquid chromatography. Structure identification of metabolites using proton nuclear magnetic resonance, mass spectroscopy, and ultraviolet/visible spectroscopy indicated that hydroxylations at benzylic C1 and at the C7- and C12-CH3 functions are major oxidation products of THDMBA. Major metabolites for the noncarcinogenic 5F-THDMBA are the C4-hydroxy, C7-hydroxymethyl, and C12-hydroxymethyl derivatives. However, the potent carcinogen 6F-THDMBA only yielded major hydroxylation products at C1 and C12-CH3. These results together with a consideration of the electronic and steric effects of fluorine and the biological activities of these polycyclic aromatic hydrocarbons suggest that hydroxylation at the hindered benzylic C1 position or the C12-CH3 group of THDMBA is important for the biotransformation of such polycyclic aromatic hydrocarbons to DNA-bonding species. PMID- 1591720 TI - Influence of the H-ras oncogene on radiation responses of a rat rhabdomyosarcoma cell line. AB - Rat R2k rhabdomyosarcoma cells were transfected with the human H-ras oncogene, which resulted in increased resistance to cell kill in vitro by a single dose of 137Cs gamma-rays. A subline carrying one oncogene showed an increase in the quasi threshold dose (Dq) from 0.88 to 1.48 Gy. Another subline containing six oncogenes not only had an increased Dq of 1.59 Gy but also showed an increase in the dose reducing cell survival to a fraction of e-1 = 0.37 (D0) from 1.25 to 1.76 Gy. Analysis of the cell survival data according to the linear-quadratic formalism indicated that a decrease in the value of the coefficient of the linear component alpha is associated with a H-ras-mediated increase in radioresistance. In fractionated irradiation experiments it was observed that with a dose of 1 Gy/fraction a 1.8 times higher dose for an isoeffect of 10% cell survival (D10) was needed for a subline with one H-ras oncogene, while with fraction doses of 2 or 4 Gy only a 1.2 times higher D10 was found. This indicates a more efficient repair of radiation-induced damage in the transfected subline. Tumors arising in the rat gastrocnemius muscle inoculated with cultured cells were irradiated with different doses of 300-kV X-rays. A single dose of 45 Gy was found to result in a 6% cure rate for the subline containing one H-ras oncogene and a 32% for the parental line. When a priming dose of 45 Gy was followed by fractionated irradiation with 1 Gy/fraction, an extra dose of 51 Gy would be needed to obtain a 75% cure rate for the transfected subline. An extra dose of only 10 Gy would be needed for the parental line. The percentage cure per unit of dose for the parental line irradiated with 1 Gy/fraction was estimated to be 4.3%.Gy-1, whereas for the transfected tumor line it was 1.4%.Gy-1. This means that a 3.0 times higher cumulated absorbed dose would be needed for enhancing the cure rate from 32% to 75% in the subline with H-ras than for the parental line. With 2 Gy/fraction the difference in extra doses required for obtaining isolevels of cure rates was found to be small, a factor of 1.4. The results indicate that in the course of fractionated irradiation with 1 Gy/fraction, in vivo repair is much more efficient in the transfected subline. PMID- 1591721 TI - Overexpression of the ras-related rab2 gene product in peripheral blood mononuclear cells from patients with hematological and solid neoplasms. AB - The rab2 gene product belongs to the rab branch of the ras-related GTP-binding protein family. The rab2 gene mRNA analysis in 70 tumor samples from various origins showed no obvious difference between malignant tissues and their normal counterparts. However, an over-expression has been observed at the RNA or protein levels in peripheral blood mononuclear cells from the nine patients with Sezary syndromes studied. Subsequent investigations in mycosis fungoides and solid tumor patients allowed us to link these high protein levels to immune reactive rather than to malignant cells. Circulating monocyte and lymphocyte populations from cancer patients are under analysis to correlate the Rab2 protein overexpression to a peculiar subset of cells. PMID- 1591722 TI - Frequent loss of heterozygosity at the DCC locus in gastric cancer. AB - We examined 28 cases of surgically resected gastric cancer, excluding the diffuse type, for loss of heterozygosity (LOH) on 12 chromosomal arms using polymorphic DNA markers. LOH on chromosome 18q was detected in 61% (14 of 23) of the cases by the probes OLVIIA8, OLVIIE10, p15-65, SAM 1.1, and OS-4, and a putative common region showing LOH included the locus of the DCC tumor suppressor gene. LOH on chromosome 17p was also frequently found (8 of 19 or 42% of the cases) by the probes p10-3 and pHF12-1, and in 5 of these 6 cases the LOH on chromosome 17p was accompanied by LOH on chromosome 18q. On the other hand, the incidence of LOH was 30% or less using probes pHRnES, pHF12-65, p-c-mybE2.6, NJ3 3.2, pHF12-8, pHINS6.0, p9D11, hp2-alpha, pCMM6, and P1A5 on chromosomes 1q, 5, 6q, 7q, 9, 11p, 13q, 16q, 20, and 22q, respectively. LOH on chromosome 18q was frequent irrespective of the depth of tumor invasion, whereas the incidence of LOH on chromosome 17p was higher in the cases in which the tumor invaded beyond the muscularis propria than in those in which tumor invasion was limited to the submucosa and muscularis propria. These results suggest that LOH on chromosome 18q occurs at an earlier stage than LOH on chromosome 17p and that the inactivation of tumor suppressor genes located on chromosome 17p and 18q (e.g., the p53 and DCC genes) is critically involved in the development of the majority of gastric cancers. While alteration of the p53 gene is observed in various human cancers, that of the DCC gene is considered to occur more selectively in gastrointestinal cancers. PMID- 1591723 TI - Parathyroid hormone-like peptide shares features with members of the early response gene family: rapid induction by serum, growth factors, and cycloheximide. AB - The parathyroid hormone-like peptide (PLP) gene is widely expressed in normal and neoplastic tissues. Previous studies have demonstrated that PLP gene expression is regulated by serum and cycloheximide, features common to the regulation of a number of different early response genes. We now report that PLP mRNA transcripts are induced within 5 min of exposure of rat keratinocytes to serum, return to control values at 20 min, and then increase and remain elevated for at least 4 h, following which they return to baseline levels. The PLP mRNA t1/2 was approximately 90 min in both serum-deprived and serum-stimulated cells. The serum induction was blocked by actinomycin D. Cycloheximide alone induced PLP gene expression; however, PLP mRNA transcripts were not superinduced in the presence of both serum and cycloheximide. Dexamethasone and 1,25-dihydroxyvitamin D3 inhibited the basal levels of PLP mRNA transcripts but did not eliminate the serum induction of PLP gene expression. Epidermal growth factor or transforming growth factor-beta alone induced PLP mRNA transcripts, but no induction was observed following exposure of cells to epidermal growth factor and transforming growth factor-beta together. Treatment with 12-O-tetradecanoylphorbol-13-acetate for 90 min did not induce PLP mRNA transcripts, but 12-O-tetradecanoylphorbol-13 acetate blocked the rapid serum induction of PLP gene expression. These features of PLP gene expression suggest that PLP is a member of the growth factor regulated early response gene family. The rapid serum stimulation of PLP gene expression raises the possibility that PLP may contribute in an autocrine fashion to the early cellular response to growth factor stimulation. PMID- 1591724 TI - Characterization of a cisplatin-resistant human ovarian carcinoma cell line expressing cross-resistance to 5-fluorouracil but collateral sensitivity to methotrexate. AB - In vitro exposure of the TR170 ovarian carcinoma cell line to six intermittent 24 h treatments with a 90% inhibitory concentration of cisplatin (CDDP) (0.15 micrograms/ml; 0.5 microM) resulted in a 2-fold stably resistant subline designated TR170/CP+ (B.T. Hill et al., Int. J. Cancer, 39: 219-225, 1987). Resistance to CDDP in these CP+ cells has now been associated with reduced uptake of 195mCDDP (2-fold; P less than 0.01) and decreased removal of specific Pt-DNA adducts, quantitated immunochemically, indicative of an apparent increased tolerance of CDDP-induced DNA damage. Specifically these resistant cells appeared deficient in removal of the major cis-Pt-(NH3)2d(pGpG) adduct and the difunctional cis-Pt(NH3)2d(GMP)2 lesion, showed less efficiency in removing cis Pt(NH3)2d(pApG) adducts, but proved as proficient as the parental cell line in removing DNA-DNA interstrand cross-links. Activities of DNA polymerase-alpha and beta were comparable in both lines, and no significant alterations in glutathione metabolism were identified. Response to acute X-irradiation was not modified in these TR170/CP+ cells, but they showed marked (10-fold) cross-resistance to 5 fluorouracil and, unusually, proved collaterally sensitive (12-fold) to methotrexate. Resistance to 5-fluorouracil was associated with significantly increased thymidylate synthase activity (P less than 0.01), but this was not reflected in altered gene expression, while increased sensitivity to methotrexate was accompanied by increased drug uptake but by unaltered activity and expression of dihydrofolate reductase. These results indicate that exposure to CDDP can result in numerous alterations, both intracellularly and at the cellular membrane, reflected in significant changes in the tumor cells' responses to the cytotoxic effects of a range of antitumor drugs. The clinical relevance of these observations remains to be established. PMID- 1591725 TI - Sensitization of human cervical carcinoma cells to cis diamminedichloroplatinum(II) by bryostatin 1. AB - Bryostatins are an important class of protein kinase C (PKC) activators. We have investigated the effect of bryostatin 1 on the antiproliferative activity of cis diamminedichloroplatinum(II) (CP). A 24-h pretreatment of HeLa cells with 1 nM bryostatin 1 increased cellular sensitivity to CP by 4-fold. The effect of bryostatin 1 on the IC50 of CP (concentration of drug required to inhibit cell proliferation by 50%) was concentration-dependent and biphasic; the maximum effect of bryostatin 1 was seen with 1 nM, but higher concentrations of bryostatin 1 (greater than or equal to 10 nM) produced less CP sensitization. Although bryostatin 1 and phorbol esters caused an equivalent stimulation of HeLa cell PKC in cell-free systems, bryostatin 1 was less effective than phorbol esters in sensitizing cells to CP. Additionally, higher concentrations of bryostatin 1 (greater than or equal to 10 nM) antagonized CP sensitization by phorbol esters. Bryostatin 1 was even more potent than 12-O-tetradecanoylphorbol 13-acetate in inducing PKC down-regulation, and the maximum down-regulation was achieved with 10 nM bryostatin 1. Bryostatin 1 also increased cellular sensitivity to a CP analogue, cis-dichloro(ethylenediamine)platinum(II). A 24-h pretreatment with 1 nM bryostatin 1 increased cellular cis-[3H]DEP by 60%. The concentration- and time-dependent enhancement in CP sensitivity by bryostatin 1 was related to the increase in cis-[3H]DEP level. Thus, cellular accumulation of CP may be regulated by a PKC-dependent phosphorylation event. PMID- 1591726 TI - Antibody drug carrier for immunotherapy of superficial bladder cancer: ultrastructural studies. AB - Superficial bladder cancer represents a promising target for intravesical, antibody-guided therapy. The construction of an optimum antibody-cytotoxic drug conjugate depends mostly on the appropriate selection of a monoclonal antibody (mAb). We have used immunogold labeling and SEM to specifically map the distribution of antigens expressed on three bladder cancer cell lines and on the luminal surface of biopsies from human transitional cell carcinoma of various grades and from normal bladder mucosa. The 48-127 mAb, which recognizes a M(r) 54,000 surface glycoprotein (gp54), was found to be very promising as a potential drug carrier. This antibody reacts with the surface of cells from low- and high grade tumors; it does not react with the normal urothelium. Labeling of normal bladder mucosa was observed, however, on microvillous intermediate urothelial cells occasionally exposed by small areas of desquamation. The 48-127 mAb could target drugs to all areas of transformed urothelium while avoiding drug delivery to the normal, undesquamated bladder mucosa. Kinetics of gp54/48-127/gold complexes were tested in vitro with T24 and RT4 human bladder carcinoma cell lines incubated in the presence of the 48-127 mAb directly conjugated with 17.7 nm gold particles. Internalization of the gp54/48-127/gold complex was readily demonstrated by transmission electron microscopy. These results suggest that the 48-127 mAb represents a valuable drug carrier for intravesical therapy, allowing specific tumor targeting and internalization of various cytotoxic agents. PMID- 1591727 TI - Drug transport mechanisms in HL60 cells isolated for resistance to adriamycin: evidence for nuclear drug accumulation and redistribution in resistant cells. AB - HL60 cells isolated for resistance to Adriamycin are multidrug resistant and defective in the cellular accumulation of drug. These cells do not contain detectable levels of P-glycoprotein. At the present time the mechanism by which HL60/Adr cells reduce drug levels is not known. To gain insight into the molecular basis of this system we have analyzed transport pathways and the distribution of daunomycin in drug-resistant HL60 cells. Using a cell fractionation technique we find that the major portion of daunomycin accumulates in the nucleus of both sensitive and resistant cells. Further studies reveal, however, that under efflux conditions drug is retained in the nuclei of sensitive cells but rapidly removed from the nuclei of the resistant isolate. Essentially identical results are obtained when daunomycin distribution and transport are analyzed by fluorescence microscopy. A number of agents which alter transport processes have been tested for their effect on drug accumulation in resistant cells. Thus we find that brefeldin A, which disassembles Golgi, and various lysosomotropic agents such as chloroquine and methylamine do not affect drug levels. In contrast the protonophores nigericin and monensin induce an increase in drug accumulation and inhibit efflux. The results of this study thus suggest that resistance in HL60/Adr cells is related to a mechanism whereby drug is transported to the nucleus and thereafter rapidly redistributed to the extracellular space. The molecular basis of this transport pathway is not known. PMID- 1591728 TI - Role of the alveolar type II cell in the development and progression of pulmonary tumors induced by 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in the A/J mouse. AB - The role of the type II cell in the development of pulmonary tumors induced in the adult A/J mouse (6 weeks of age) by treatment with a single dose (100 mg/kg, i.p.) of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) was investigated. Twenty-four h following treatment with NNK, the concentration of O6-methylguanine was similar in Clara and type II cells. However, hyperplasias were detected only along the alveolar septa in lungs 14 weeks after carcinogen treatment. Examination of the ultrastructure of several hyperplasias revealed that the proliferating cells resembled type II pneumocytes. The proliferating cells were cuboidal in shape, with centrally localized ovoid nuclei characterized by minor indentations. Lamellar bodies, one of the major hallmarks of the type II cell, were present in the cytoplasm. The progression of pulmonary lesions was followed by sacrificing mice at 4-week intervals from 14 to 54 weeks after treatment with NNK. From 34 to 42 weeks after treatment, progression to neoplasia was demonstrated by a decline in the frequency of hyperplasias and an increase in the frequency of adenomas. Approximately 50% of the adenomas were observed arising within hyperplasias. Carcinomas appeared to increase in frequency 34 weeks after carcinogen treatment and comprised greater than 50% of the pulmonary lesions by 54 weeks. Approximately 30% of the carcinomas were observed arising within adenomas. The growth pattern of carcinomas began to change from solid to mixed (solid and papillary) 42 weeks after NNK. Moreover, electron micrographic analysis demonstrated that, within a hyperplasia, proliferating type II cells could change from cuboidal to columnar in shape and could also exhibit nuclear indentations, both characteristics displayed by the Clara cell. Thus, this divergence of the type II cell from its well characterized morphological features indicates that the selective growth advantage which these initiated cells possess can result in changes to the normal ultrastructure of this cell as it progresses toward malignancy. DNA was isolated from 20 hyperplasias and screened for the presence of an activated K-ras gene. This gene was activated in 17 of 20 lesions, with 85% of the mutations involving a GC to AT transition within codon 12 (GGT to GAT), a mutation consistent with base mispairing produced by the formation of the O6-methylguanine adduct. This specificity for activation of the K-ras gene was identical to that observed previously in adenocarcinomas induced by NNK.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1591729 TI - Antitumor effects of B3-PE and B3-LysPE40 in a nude mouse model of human breast cancer and the evaluation of B3-PE toxicity in monkeys. AB - B3 is a tumor-reactive monoclonal antibody (mAb) that binds to a limited number of normal tissues. Immunotoxins made with B3 coupled to either Pseudomonas exotoxin (PE) or recombinant forms of PE with a deletion of the cell-binding domain (LysPE40) have been shown to cause complete tumor regression in nude mice bearing a rapidly growing A431 (L. H. Pai et al., Proc. Natl. Acad. Sci. USA, 88: 3358-3362, 1991) human epidermoid carcinoma. In this study we show that an immunotoxin composed of mAb B3 when chemically coupled to LysPE40 (B3-LysPE40) led to complete regression of a slowly growing breast cancer, MCF-7, in nude mice when given i.v. every other day for five doses. mAb B3 coupled to native PE also produced significant regression of the MCF-7 tumor. The reactivity of mAb B3 was evaluated using an immunohistochemical method on the two responsive tumors, MCF-7 and A431, and compared with a typical human colon carcinoma specimen that has B3 antigen on its surface. The results showed that both A431 and MCF-7 xenograft tumors have similar reactivity to B3 when compared with the human colon carcinoma specimen. To evaluate the toxicity of B3-PE in primates, Cynomolgus monkeys received escalating doses of B3-PE i.v. on Days 1, 3, and 5. Based on antibody localization studies using frozen sections of normal human and monkey tissue, gastric, trachea, and bladder mucosal injury could have occurred. However, no clinical signs of injury or histological damage to these organs were seen at the doses administered. Chemical hepatitis due to PE was transient and well tolerated at doses up to 50 micrograms/kg for three doses. The lethal dose was about 100 micrograms/kg, and the cause of death was liver necrosis, as shown by necropsy. We conclude that mAb B3, when coupled to PE40 or PE, can produce strong antitumor activity in vivo. The similar level of reactivity of the B3 antibody in our tumor models with a surgical specimen of a human colon carcinoma and the toxicity study in monkeys indicate that therapeutic doses of B3-PE and B3-LysPE40 can be delivered without causing toxicity to normal organs that express B3 antigen. Although both B3-PE and B3-LysPE40 have antitumor activity in nude mice bearing a human xenograft, B3-LysPE40 is better tolerated and should be further evaluated as a therapeutic agent for cancer patients. PMID- 1591730 TI - In vivo efficacy of a novel inhibitor of selected signal transduction pathways including calcium, arachidonate, and inositol phosphates. AB - Aberrant signal transduction has been implicated in malignant transformation, growth, and progression. This has led to the proposal to use inhibitors of signal transduction pathways to treat cancer. One approach to circumventing potential toxicity and improving efficacy would be to target pathways upon which cancer cells selectively depend. Pathways associated with the malignant process involve calcium fluxes, the release of arachidonic acid, and the generation of phosphoinositides. In this report, CAI (L651582, NSC 609974), a substituted carboxyamido-imidazole and novel inhibitor of these selected signal transduction pathways, inhibits anchorage-dependent and -independent growth in a large series of human cancer cell lines. CAI pretreatment of HT-29 human colon cancer and 5R ras-transfected rat embryo fibroblast cells inhibits the formation and growth of experimental pulmonary metastases in nude mice. Oral administration of CAI in PEG 400 vehicle arrests growth and metastasis of transplanted human melanoma and ovarian cancer xenografts. No significant gross or histological toxicity was observed at CAI doses yielding blood levels in the concentration range demonstrated to inhibit select signal transduction pathways in vitro. These data indicate the feasibility and demonstrate a potential selectivity and sensitivity of using specific signal transduction inhibitors for the experimental treatment of cancer. PMID- 1591731 TI - Amphiregulin messenger RNA is elevated in psoriatic epidermis and gastrointestinal carcinomas. AB - Amphiregulin (AR) is a heparin-regulated, epidermal growth factor-like growth factor capable of stimulating the proliferation of non-tumorigenic cells while inhibiting cell proliferation in some human tumor cell lines in vitro. In the present study, we have investigated AR mRNA expression in normal, hyperproliferative, and neoplastic human epithelium. Our results demonstrate that, compared with the adjacent uninvolved epithelium, AR mRNA expression is markedly elevated in epidermal biopsies derived from three human psoriatic lesions as well as in biopsies derived from five human colon carcinomas and three human stomach carcinomas. Moreover, analysis of a colon carcinoma by in situ hybridization revealed that AR mRNA is localized to the epithelium. PMID- 1591732 TI - Screening for germ line TP53 mutations in breast cancer patients. AB - The constant denaturant gel electrophoresis technique was used to screen for TP53 germ line mutations in 237 women with breast carcinoma (167 unselected patients, 30 patients with at least one first-degree relative with breast cancer, and 40 women diagnosed with breast cancer before age 35). A germ line mutation at codon 181 was noted in one of the unselected patients and a codon 245 mutation in one of the early-onset patients. Both had a family history of breast cancer and other malignancies suggestive of Li-Fraumeni syndrome. The codon 245 mutation was also present in this patient's affected mother. PMID- 1591734 TI - Third annual Pezcoller symposium: tumor suppressor genes. PMID- 1591733 TI - Increased accumulation of drugs in multidrug-resistant cells induced by liposomes. AB - A multidrug-resistant cell such as the human lymphoblastic leukemic cell CEM/VLB100 accumulates far less vinblastine (VLB) than its drug-sensitive parent, CEM. When CEM/VLB100 cells are exposed to liposomes consisting of the phospholipids cardiolipin, dioleoylphosphatidic acid, or phosphatidylinositol bearing unsaturated fatty acids and then tested for uptake of VLB, accumulation of drug rapidly rises to levels approaching those of CEM cells, which are relatively unaffected by the liposome treatment. The liposomes are not carriers of entrapped drug. Phosphatidylserine, phosphatidylcholine, and phosphatidylethanolamine are inactive, and the addition of cholesterol to liposomes inhibits uptake. Exposure of cells to liposomes does not appear to alter the efflux of drugs. We suggest that the liposomal lipids, introduced into the plasma membranes of CEM/VLB100 cells, change their properties so that accumulation of drugs by cells is largely restored. The cytotoxicity of VLB in CEM/VLB100 cells is increased approximately 10-fold by cardiolipin liposomes. PMID- 1591735 TI - Chronic administration of L-dopa affects the movement-related cortical potentials of patients with Parkinson's disease. AB - The chronic effect of L-Dopa administration on the movement-related cortical potentials (MRCPs) was studied in two groups of patients with Parkinson's disease (PD): patients de novo (DN) and patients with on-off fluctuations. The BP and NS' premovement components of MRCPs associated with wrist flexion were assessed by their gradients and by their distribution on the midline (CZ) and the ipsilateral and contralateral hand sensorimotor areas. The treatment efficacy was controlled by a decrease in PD score (Columbia University Rating Scale). The BP component was absent in four out of nine patients DN. After 3 months of treatment, BP and NS' were recorded in six out of seven patients, and the NS' slope was significantly increased in all patients. In the off phase, MRCPs from patients with on-off fluctuations did not present a BP component. In the on phase, the NS' slope was increased and the BP was recorded in two out of nine patients. These patients exhibited an earlier PD stage (Hoehn and Yahr, stage 3). These two patterns of changes in the MRCPs induced by L-Dopa treatment suggest that the BP component was recorded in patients DN when a partial resolution of the nigrostriatal activity could occur. In patients with severe fluctuations, the dopaminergic striatal pathway was more severely affected and the increase of the NS' component demonstrated the activation of extrastriatal dopamine sites within the central nervous system (limbic and cortical structures, in particular). PMID- 1591736 TI - Datura delirium. AB - Poisoning with tropine alkaloids from cultivated plants and pharmaceuticals is an uncommon cause of delirium and coma. We report a patient with a toxic delirium following ingestion of the tropine alkaloid-containing root of Datura innoxia. Thin-layer chromatography and gas chromatography/mass spectrometry confirmed the presence of atropine and scopolamine in samples of the ingested root. Routine clinical toxin screens may not include an assay for tropine alkaloids. A specific tropine alkaloid assay may provide supporting evidence. The clinical, electroencephalographic, and therapeutic aspects of anticholinergic poisoning are discussed. PMID- 1591737 TI - The effects of milacemide on item and source memory. AB - Prior research has shown that memory for facts and items (item memory) and memory for where one has learned these items (source memory) can be dissociated under certain conditions. In this study, we examined the effects of milacemide, a derivative of glycine, on memory for item and source information in healthy young and older adults. These results pointed to a dissociation between source memory and item memory: Milacemide administration seemed to facilitate memory for source information but did not affect recognition memory. PMID- 1591738 TI - Action of nimodipine on sympathomimetic mydriatics in humans. AB - In 12 healthy volunteers, the effects of a single oral dose of nimodipine (40 mg) on pupil size and on the mydriasis induced by conjunctival instillation of tyramine and phenylephrine were studied by using a TV monocular infrared pupillometer. Nimodipine alone was unable to modify the pupil area. When compared with placebo, the Ca2+ entry blocker reduced the pupil dilation caused by tyramine, whereas it did not affect the phenylephrine-induced mydriasis. Since tyramine provokes mydriasis by releasing neuronal norepinephrine, a full adrenoceptor agonist, whereas phenylephrine acts only on alpha 1-adrenoceptors insensitive of extracellular Ca2+, the hypothesis may be advanced that a heterogeneous population of alpha-adrenoceptors, located in the human iris dilator muscle and differently sensitive to Ca2+ entry blockade, is responsible for the reduction of the tyramine-induced mydriasis. Apart from this putative mechanism, the results suggest that nimodipine reduces the pupillary response to adrenergic activation in the human eye. PMID- 1591739 TI - Tizanidine in cranial dystonia. AB - Recent electrophysiological studies in patients with cranial dystonia (CD) have demonstrated evidence for hyperactivity of brainstem interneurons. Tizanidine (Tz), a centrally acting skeletal muscle relaxant, is thought to act by antagonizing the activity of excitatory interneurons which mediate hypertonic processes (e.g. spasticity). Theoretically this agent may be effective in patients with CD. Ten patients were enrolled in an open-label study with a single blind placebo wash-in. Eight patients tolerated doses of between 28-36 mg per day. For the most part tizanidine was ineffective for the symptoms of CD. This failure suggests that the reported brainstem interneuronal disturbances may not be altered by Tz. Further studies using concomitant electrophysiological assessment would be necessary to assess this possibility. Alternatively, these disturbances may not be a principle cause of the dystonic movements. The finding of similar changes in other basal ganglia diseases lacking CD (e.g. Parkinson's disease) favours this latter explanation. PMID- 1591740 TI - Clonidine and prolactin secretion in humans. PMID- 1591741 TI - Classification of essential tremor. AB - Classification of essential tremor was attempted using tremor frequency; tremor duration; family history of tremor; responsiveness to alcohol, propranolol, and primidone; muscle contraction pattern; and long-latency reflexes. Sixty-one patients were evaluated. The majority of patients had a tremor frequency less than 7.0 Hz, a positive family history, and a positive response to alcohol. Approximately 46% of patients had a beneficial response with propranolol and 71% with primidone. Tremor frequency was inversely correlated with age and directly correlated with an antagonist pattern of muscle contraction. Enhanced long latency reflexes were not found. Other characteristics of essential tremor were not significantly correlated. It is concluded that essential tremor can not be classified into subtypes. PMID- 1591742 TI - Cigarette smoking and Parkinson disease: the illusion of a neuroprotective effect. AB - Repeated studies have demonstrated a negative association between cigarette smoking and Parkinson disease. This negative association has led many investigators to suggest that some facet of cigarette smoking exerts a neuroprotective influence with respect to developing Parkinson disease. Longitudinal Gompertzian analysis demonstrates that no neuroprotective influence is necessary to account for the negative association between Parkinson disease and cigarette smoking. Indeed, the only assumption that needs to be made is that smokers experience earlier mortality than nonsmokers. The example of cigarette smoking and Parkinson disease illustrates a limitation with current risk factor analysis, i.e., disease patterns are typically interpreted using only two dimensions: genetics and the environment. However, longitudinal Gompertzian analysis demonstrates that disease mortality patterns and trends are actually three-dimensional phenomenon, with competition being the third dimension. PMID- 1591743 TI - Intracranial arachnoidal cysts. AB - Twenty-eight cases of intracranial arachnoidal cysts diagnosed during the period 1978-1990 are analyzed. All cases were investigated with computed tomography (CT), 5 with magnetic resonance imaging (MRI) and 5 with ultrasonography (US). Seventeen were located in the middle cranial fossa, 3 in the quadrigeminal cistern, 2 were parasagittal, 3 suprasellar and 3 were located in the posterior fossa. Twenty-three of the 28 patients were treated surgically, craniotomy with fenestrations was used in 3 cases. Different varieties of shunts were inserted in 8 cases and in the last 15 patients the only surgical treatment was the insertion of cysto-peritoneal (CP) drainage (without a valve) with excellent results. MRI and/or CT follow-up revealed disappearance of the cyst in 13 out of 22 cases and 7 experienced a marked reduction. In 2 patients the cyst showed little change. There were no cases of infection and no deaths. PMID- 1591745 TI - Mature sacrococcygeal teratoma containing the lower half of a human body. AB - Twins were diagnosed by ultrasound in a 29-year-old woman. The cesarean delivery revealed at first a mature girl with a large benign sacrococcygeal teratoma and then a healthy boy. X-ray and CT examinations of the teratoma showed pelvic and lower limb bones. A mature teratoma-tridermoma (weight 475 g) containing the underdeveloped lower half of a human body was confirmed during surgery and verified morphologically. The fraternal twins, i.e., the girl operated upon and her brother, have been followed for 5 years and are without any complaints. They have normal neurological function. PMID- 1591744 TI - Enterogenous cyst in the thoracic spinal canal in association with a syringomeningomyelocele. AB - A thoracic intradural extramedullary enterogenous cyst in association with a syringomeningomyelocele in a 5-year-old boy is presented. The pathogenesis of this rare association is discussed and the pertinent literature reviewed. PMID- 1591746 TI - Myoclonic dystonia. AB - Myoclonic dystonia is a rare disorder that occurs in an hereditary and a sporadic form. The autosomal-dominantly inherited form is responsive to alcohol but not to other drugs. The sporadic form has been relatively resistant to drug treatment. We report a young man with myoclonic dystonia who displayed only little response to alcohol but improved significantly with a combination of sodium valproate for myoclonus and trihexiphenidyl hydrochloride for dystonia. His rehabilitation, however, was confounded by public authorities who thought the patient's appearance was indicative of drug use. PMID- 1591747 TI - Craniofacial growth in shunt-treated hydrocephalics: a four-year roentgenocephalometric follow-up study. AB - The craniofacial growth of 24 shunt-treated hydrocephalics aged 5-15 years was evaluated over a 4-year period, by comparing changes in linear and angular cephalometric variables with those of an age- and sex-matched control group. The main findings were increased calvarial thickness, increased cranial base flexure, superior displacement of the sella, and a tendency for the gonial angle to remain more obtuse in the shunt-treated patients. As craniofacial growth in the latter differed only slightly from that observed in the controls, the deviations in facial morphology observed in a previous cross-sectional study of shunt-treated hydrocephalics can be taken to represent a long-term effect of the shunt treatment. PMID- 1591748 TI - Assessment of craniocerebral asymmetries in children by computed tomography. AB - Computed tomographic (CT) scans of 32 children (mean age 2.8 +/- 2.5 years) with a wide range of craniocerebral asymmetry (CCA) were analyzed. Hemiparesis and epilepsy were the main clinical presentations. Two-thirds of the patients had brain infarcts. The degree of cerebral and ventricular asymmetry was evaluated by ratios obtained by linear measurements. The patients were divided into two groups according to the index of maximal asymmetry. The incidence of hemiparesis and the width of the cerebral ventricles did not differ in the two groups. This may be due to the fact that most of our patients suffered from perinatal insult to the brain, allowing time for remodeling and plastic changes to occur. The use of measurable structural parameters in craniocerebral asymmetry offers a basis for comparable radiological assessment. PMID- 1591749 TI - Magnetic resonance imaging analysis of extremely slow flow in a model shunt system. AB - Shunt malfunction is common and its diagnosis may require invasive testing that may be inaccurate or result in complications. Magnetic resonance imaging (MRI) may prove to be a useful noninvasive test of shunt function as it has been shown that MRI is capable of measuring cerebrospinal fluid (CSF) flows from 2 ml/h to 40 ml/h in model systems. Since flows in functioning shunt systems can be less than 2 ml/h, MRI must be sensitive enough to detect flow in this range in order to be a valid test for shunt function. Continuing previous studies, we have studied MRI flow-related enhancement at flow rates from 0 to 2 ml/h. Multiple spin echo scans (TR2000, TE20) were made through a specialized section of tubing in a model shunt system. The intensity of the MRI signal at points known to demonstrate maximal flow-related enhancement was measured. A linear relationship was demonstrated between signal intensity and flow as low as 0.8 ml/h. These results add support to the concept that MRI is sensitive enough to detect the lowest flows present in functioning shunt systems and therefore may be useful as a noninvasive test of shunt function. PMID- 1591750 TI - Evaluation of cerebrospinal fluid shunt function in hydrocephalic children using 99mTc-DTPA. AB - The increasing numbers and survival of children with shunt-treated hydrocephalus make it mandatory to refine the methods for cerebrospinal fluid (CSF) shunt function evaluation. Radionuclide shuntography with 99mTc-DTPA, which has proved to be a safe and effective method, was performed in eight children with suspected CSF-shunt dysfunction. Characteristic shuntography patterns were found for proximal and distal CSF-shunt catheter obstruction as well as for overdrainage and normal CSF-shunt function. Shuntography contributed to the explanation of suspected CSF-shunt dysfunction in all children investigated. PMID- 1591751 TI - Central diabetes insipidus in hypoxic brain damage. AB - We describe two children who after cardiopulmonary arrest developed hypernatremia at the terminal stage. Urinary antidiuretic hormone concentration was very low, indicating central diabetes insipidus. These cases illustrate the necessity of alertness to the development of central diabetes insipidus in patients with severe hypoxic brain damage. PMID- 1591752 TI - Anatomical progression of the Chiari II malformation. AB - To evaluate whether anatomic change of the relationship of the Chiari II malformation and the cranial base was occurring, 22 children with meningomyelocele had serial MRI scans reviewed. A ratio (B/A) was established between the distance from the foramen magnum to the caudalmost portion of herniated cerebellum (B) and the diameter of the foramen magnum (A) and this ratio was compared on serial MRI scans. Eighteen children had an increase in the B/A ratio, two children had a decrease, and two had no change. This indicates that continuous anatomic change of the Chiari II malformation and the skull base is occurring. Clinical deterioration in the older child may be explained by a combination of compressive and traction forces due to this change. PMID- 1591753 TI - Long-term outcome and complications of children born with meningomyelocele. AB - The long-term functional outcome of 101 children born with meningomyelocele between 1971 and 1981 was assessed, by a combination of retrospective chart review and follow-up assessments. The children had been managed at birth using a process of nonstandardized selection. Eighty-three of the 101 patients survived after a minimum follow-up of 8.6 years, for a mortality rate of 18%. Forty-four of 83 children (53%) were community ambulators, and this correlated well with the presence of intact quadriceps function. Forty-eight children (58%) attended normal school and were grade-appropriate. Sixty-two of 83 patients (75%) were socially continent of urine, and 71/83 (86%) were socially continent of stool. Hydrocephalus was present in 93 of the 101 children in the study, and 85 children were shunted. Half of the shunted children required a shunt revision in the first year of life, and thereafter the rate of revision decreased, so that after 2 years the risk of revision was approximately 10% per year. PMID- 1591754 TI - Scoliosis associated with syringomyelia presenting in children. AB - The clinical presentations and radiological features of scoliosis accompanying syringomyelia were analyzed in 14 cases of syringomyelia associated with a in 14 cases of syringomyelia associated with a Chiari malformation in children. Scoliosis was the initial symptom in 11 out of 16 patients (64%) with syringomyelia and present in 14 (88%) at the initial examination. The scoliosis associated with syringomyelia was characterized by a higher incidence of a single curve (6 cases, 43%) and convexity to the left (7 cases, 50%) than seen in idiopathic scoliosis. The syrinx was shifted to the convex side of scoliosis on the axial section at the middle or lower thoracic level in patients with a single curve, and at the cervical or upper thoracic level in patients with a double curve. The authors think that the scoliosis develops in children as a result of damage done to the anterior horn, which innervates the muscles of the trunk, by an asymmetrically expanded syrinx. PMID- 1591755 TI - Roles of potassium ions, acetyl and L-glyceryl groups in native gellan double helix: an X-ray study. AB - Native gellan, the natural form of the polysaccharide excreted by the bacterium Pseudomonas elodea, has a tetrasaccharide repeating unit that contains L-glycerol and acetate ester groups, and forms only weak and elastic gels. Based on X-ray diffraction data from well oriented and polycrystalline fibers of its potassium salt, the crystal structure of native gellan, including ions and water, has been determined and refined to a final R-value of 0.17. The molecule forms of a half staggered, parallel, double helix of pitch 5.68 nm which is stabilized by hydrogen bonds involving the hydroxymethyl groups in one chain and both carboxylate and glyceryl groups in other. Two molecules are packed in an antiparallel fashion in a trigonal unit cell of side a = 1.65 nm. Although the gross molecular morphology and packing arrangements are isomorphous with those observed in the crystal structure of potassium gellan, which is devoid of any substitutions, native gellan exhibits exceptional changes in its ion binding characteristics with respect to gellan. In particular, the L-glyceryl groups do not allow the gellan-like coordinated interactions of the ions and the carbohydrate groups, within and between double helices, which are necessary for strong gelation. These results at the molecular level explain, for the first time, the differences in the behavior of the polymer with and without substitutions. PMID- 1591756 TI - Synthesis of nigero-oligosaccharides. AB - Nigerose [alpha-D-Glcp-(1----3)-D-Glcp], nigerotriose, nigerotetraose, and nigeropentaose have been synthesized by chain elongation starting at the reducing end, from the corresponding octa-, undeca-, tetradeca-, and heptadeca-beta-D acetates, respectively, via thioglycoside-mediated 1,2-cis coupling, using 1,2,4,6-tetra-O-acetyl-beta-D-glucopyranose as the glucosyl acceptor and methyl 2,3,4,6-tetra-O-benzyl-1-thio-beta-D-glucopyranoside, methyl 3-O-allyl-2,4,6-tri O-benzyl-1-thio-beta-D-glucopyranoside, and methyl O-(2,3,4,6-tetra-O-benzyl alpha-D-glucopyranosyl)-(1----3)-2,4,6-tri-O- benzyl-1-thio-beta-D glucopyranoside as the donors. PMID- 1591757 TI - Synthesis of sialic acid-containing nucleotide sugars: CMP-sialic acid analogs. AB - Syntheses of some sialic acid-containing nucleotide sugars are reported. The reaction of methyl [(2-hydroxy)ethyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5 dideoxy-D-glycero-alpha-D-galacto -2-nonulopyranosid]onate (4) with various fully protected hydrogen phosphonates of nucleosides (5a-c) in the presence of 2,4,6 triisopropylbenzenesulfonyl chloride (TPSCl), gave, after oxidation and deprotection, the corresponding sialic acid-containing nucleotide sugar analogs (8a-c). PMID- 1591758 TI - A synthetic study of methyl 3-deoxy-3-fluoro-alpha-D-glucopyranosides from methyl 2,3-anhydro-alpha-D-allopyranosides, and synthesis of 3'-deoxy-3'-fluorokanamycin A and 3'-chloro-3'-deoxykanamycin A. AB - Reactions of 4,6-disubstituted 2,3-anhydro-alpha-D-allopyranosides with potassium hydrogenfluoride (KHF2) in ethane-1,2-diol gave, by oxirane-ring opening, the corresponding 2-deoxy-2-fluoro-alpha-D-altro- and 3-deoxy-3-fluoro-alpha-D-gluco pyranosyl derivatives, with the latter always in preponderance. The influence of the substituents at C-4 and C-6 on the D-gluco-D-altro ratio (r) have been studied by molecular mechanics, and the discrepancy between the experimental and calculated r values has been positively utilized to measure the effects of solvation and hydrogen bonding relative to the C-4 and C-6 substituents. By application of this reaction, 3'-deoxy-3'-fluorokanamycin A has been prepared by treatment of a 2',3'-anhydro-3'-epikanamycin A derivative (35) with KHF2. 3' Chloro-3'-deoxykanamycin A was also prepared. PMID- 1591759 TI - Synthesis of an S-(alpha-sialosyl)-(2----9)-O-(alpha-sialosyl)-(2----3')-beta lactos ylceramide. AB - A ganglioside GD3 analog has been synthesized having an N-acetylneuraminic acid (Neu5Ac) residue alpha-thioglycosidically linked to C-9 of the Neu5Ac residue in the ganglioside GM3 structure. Glycosylation of 2-(trimethylsilyl)ethyl O-(6-O benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O-benzoyl-beta-D glucopyranoside with methyl (methyl 5-acetamido-4,7,8-tri-O-acetyl-9-bromo-3,5,9 trideoxy-D-glycero-alpha-D- galacto-2-nonulopyranosid)onate, which was prepared from methyl (methyl 5-acetamido-3,5-dideoxy-D-glycero-alpha-D-galacto-2- nonulopyranosid)onate by 8,9-O-isopropylidenation, O-acetylation, hydrolysis of the isopropylidene group, selective bromination, and O-acetylation, using dimethyl(methylthio)sulfonium triflate (DMTST) as a promoter, gave the alpha sialosyl-(2----3')-lactoside 8. Coupling of the O-acetyl derivative of 8 with the sodium salt of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-D glycero-alpha-D- galacto-2-nonulopyranosonate gave an alpha-thioglycosidically linked tetrasaccharide. This was converted, via selective removal of the 2 (trimethylsilyl)ethyl group, trichloroacetimidation, and glycosidation with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol into a ganglioside precursor. Finally the precursor on selective reduction of the azide group, coupling with octadecanoic acid, O-deacylation, and de-esterification gave the analog, S-(N-acetyl-alpha-neuraminosyl)-(2----9)-O-(N-acetyl-9-thio-alpha- neuraminosyl)-(2----3')-beta-lactosylceramide. PMID- 1591760 TI - Synthesis of a position isomer of ganglioside GD3 having an alpha-Neu5Ac-(2----9) alpha-Neu5Ac linkage. AB - A position isomer of ganglioside GD3 has been synthesized in which N acetylneuraminic acid (Neu5Ac) is linked alpha-glycosidically at C-9 of the Neu5Ac residue of the ganglioside GM3, structure. The coupling of 2 (trimethylsilyl)ethyl O-(6-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,6-di-O benzoyl-beta-D -glucopyranoside with methyl O-(methyl 5-acetamido-4,7,8,9-tetra-O acetyl-3,5-dideoxy-D-glycero-alpha-D-galacto -2-nonulopyranosylonate)-(2----9) (methyl 5-acetamido-4,7,8-tri-O-acetyl-3,5-dideoxy-2-thio-D-glycero-D-galacto-2 nonulopyranosid)onate, prepared from the corresponding 2-(trimethylsilyl)ethyl glycoside by selective removal of the 2-(trimethylsilyl)ethyl group, 1-O acetylation, and introduction of the methylthio group with trimethyl(methylthio)silane, using N-iodosuccinimide-trifluoromethanesulfonic acid as a glycosylation catalyst, gave a tetrasaccharide (5). Compound 5 was converted, via O-acetylation, selective removal of the 2-(trimethylsilyl)ethyl group, and subsequent imidate formation, into a protected alpha-Neu5Ac-(2----9) alpha-Neu5Ac-(2----3')-alpha-lactosyl trichloroacetimidate (8). Glycosylation of (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol with 8 afforded a ceramide precursor which was transformed, via selective reduction of the azido group, coupling with octadecanoic acid, O-deacylation, and hydrolysis of the methyl ester groups, into to the little ganglioside. PMID- 1591761 TI - Application of cyclic sulfates in the synthesis of 6-deoxy-D-manno-heptopyranose derivatives. AB - 6-Deoxy-D-manno-heptopyranose was prepared in five steps starting from methyl 2,3 O-isopropylidene-alpha-D-mannopyranoside 4,6-sulfate or methyl 2,3-O isopropylidene-alpha-D-mannofuranoside 5,6-sulfate. The glycosyl donor ethyl 2,3,4,7-tetra-O-benzoyl-6-deoxy-1-thio-alpha,beta-D-manno- heptopyranoside was used to synthesize methyl 4-O-(6-deoxy-alpha-D-manno-heptopyranosyl)-beta-D galactopyranoside. PMID- 1591762 TI - Structure of a heteroglycan isolated from the fungus Omphalia lapidescens. AB - The major, water-soluble polysaccharide isolated from the sclerotia of Omphalia lapidescens, and purified by chromatography on DEAE-Sephadex A-50 and Toyopearl HW-65F, is a heteroglycan (OL-3), [alpha]D20 - 50 degrees (c 1, water), which is composed of D-glucose, 2-acetamido-2-deoxy-D-glucose, and D-glucuronic acid in the molar ratios 1.21:1.00:1.38. Methylation analysis, partial acid hydrolysis, and f.a.b.-m.s. of the hydrolysates indicated OL-3 to have a highly branched structure involving (1----3)-, (1----4)-, (1----6)-, and (1----3,6)-linked, and non-reducing terminal D-glucopyranosyl residues, and also to contain 2 acetamido 2-deoxy-beta-D-glucopyranosyl-(1----4)-beta-D- glucopyranosyluronic acid and beta D-glucopyranosyl-(1----4)-2-acetamido-2-deoxy-beta-D-glucopyranosyl -(1----4) beta-D-glucopyranosyluronic acid segments. PMID- 1591763 TI - New investigations of the structure of grape arabinogalactan-protein. AB - The structure of an arabinogalactan-protein (AGP) isolated from grape juice was studied by methylation analysis, n.m.r. spectroscopy, and interactions with peanut lectin, after specific degradation with purified enzymes and/or Smith degradation. AGP appeared to be homogeneous with a weight-average molecular weight of 110,000. Treatment of AGP with arabinofuranosidase released 88% of the arabinose and left GP1. Hydrolysis of GP1 with an endo-(1----6)-beta-D galactanase removed 50% of the galactose and left GP2. Smith degradation of GP1 gave a 3-linked galactan that still contained 3,6-linked residues. Endogalactanase- and Smith-degraded GP1, but not AGP and GP1, reacted strongly with peanut lectin. Thus, AGP is a 3-linked galactan cross-linked at positions 6. The core also carries, at positions 6, 6-linked galactan chains heavily 3 substituted with arabinofuranose residues. PMID- 1591764 TI - Structure and antitumor activity of a branched (1----3)-beta-D-glucan from the alkaline extract of Amanita muscaria. AB - A beta-(1----6)-branched (1----3)-beta-D-glucan(AM-ASN) was isolated from the alkaline extract of the fruiting bodies of Amanita muscaria. AM-ASN had [alpha]D 11 degrees in 0.5 M sodium hydroxide. Its estimated molecular weight was 95,000 in this alkaline solution and 260,000 in a neutral solution. The branches in the glucan were primarily single, (1----6)-linked D-glucopyranosyl groups, two for every seven residues in the (1----3)-linked main chain. AM-ASN exhibited significant antitumor activity against Sarcoma 180 in mice, and a mixture of AM ASN with mitomycin C was more effective against the tumor than mitomycin C only. PMID- 1591765 TI - Structure of the extracellular polysaccharide from slime-forming Lactococcus lactis subsp. cremoris SBT 0495. AB - The extracellular polysaccharide obtained from slime-forming Lactococcus lactis subsp. cremoris SBT 0495 is composed of D-glucose, D-galactose, L-rhamnose, and phosphate. Methylation analysis of the native and dephosphorylated polysaccharides provided information on the linkage of the sugar residues and the location of the phosphate group. N.m.r. spectroscopy confirmed the structure of the polysaccharide, which is assigned the following repeating-unit: [formula: see text] PMID- 1591766 TI - The use of glycosides of 6- and 8-acylamino-4-methylumbelliferone in studies of the specificity and properties of human lysosomal glycolipid hydrolases. AB - A series of 6- and 8-acylamino-4-methylumbelliferyl beta-D-galactopyranosides, beta-D-glucopyranosides, and alpha-L-fucopyranosides having various fatty acid residues were synthesized; 6-(9) and 8-hexadecanoylamino-4-methylumbelliferyl beta-D-galactopyranoside (10) were shown to be substrates for human galactocerebrosidase. Analogs of 9 with shorter acyl residues (octanoyl and butanoyl) were substrates for another type of beta-D-galactosidase, i.e., GM1 ganglioside-beta-D-galactosidase. The specificity of various beta-D galactosidases for synthetic D-galactopyranosides, differing in the length and position of their acylamide residue, tested with enzyme preparations from patients with two types of glycolipidosis, Krabbe's disease (galactocerebrosidase deficiency) and GM1-beta-galactosidase deficiency), suggested that 9 is a specific substrate for galactocerebrosidase in biochemical tests for Krabbe's disease. Fluorogenic 6-octanoyl- and 6-hexadecanoyl-amino-4-methylumbelliferyl beta-D-glucopyranoside were much less readily hydrolyzed by both human and animal glucocerebrosidase than chromogenic 2-hexadecanoylamino-4-nitrophenyl beta-D glucopyranoside. Comparison of the hydrolysis of 4-methylumbelliferyl alpha-L fucopyranoside with that of 6-hexadecanoylamino-4-methylumbelliferyl alpha-L fucopyranoside by multiple forms of human alpha-L-fucosidase showed that the enzyme is capable of hydrolyzing not only hydrophilic but also synthetic, lipid like substrates. PMID- 1591767 TI - 4-Thiocellooligosaccharides. Their synthesis and use as ligands for the separation of cellobiohydrolases of Trichoderma reesei by affinity chromatography. AB - 4-Aminophenyl 1,4-dithio-beta-cellobioside (6) was obtained by treatment of methyl 2,3,6-tri-O-benzoyl-4-O-triflyl-alpha-D-galactopyranoside with the sodium salt of 1-thio-beta-D-glucopyranose, followed by acetolysis and glycosylation of the corresponding bromide with 4-aminobenzenethiol and subsequent deacylation. A similar synthesis starting with the 1-thiolate of 1,4-dithio-beta-cellobiose led to the trisaccharide 4-aminophenyl 1,4,4'-trithiocellotrioside (16). The 4 acetamidophenyl di- and tri-thiocellooligosaccharides were found to be excellent competitive inhibitors of the hydrolysis of 4-methylumbelliferyl beta-lactoside with respective Ki values of 25 and 6.5 mM. The two 4-aminophenyl oligosaccharides 6 and 16 were coupled to CH-Sepharose 4B, and the affinity gels were used for the purification of cellobiohydrolases from a crude commercial cellulolytic extract of T. reesei. Cellobiohydrolases I or II were selectively desorbed from gels bearing ligands 6 and 16. PMID- 1591768 TI - Regioselective synthesis of alpha-L-fucosyl-containing disaccharides by use of alpha-L-fucosidases of various origins. PMID- 1591769 TI - A facile synthesis of 4-O-allyl-D-xylopyranose and its use in the preparation of xylo-oligosaccharides. PMID- 1591770 TI - Location of the O-acetyl group in welan by the reductive-cleavage method. PMID- 1591771 TI - The effect of the content of D-mannuronic acid and L-guluronic acid blocks in alginates on antitumor activity. PMID- 1591772 TI - Spacer-modified disaccharide and pseudo-trisaccharide methyl glycosides that mimic maltotriose, as competitive inhibitors for pancreatic alpha-amylase: a demonstration of the "clustering effect". AB - The synthesis is reported of methyl 4,4'-dithio-alpha-maltotrioside (12) and the spacer-modified disaccharide glycosides methyl 4-S-(4-alpha-D-glucopyranosylthio 2-hydroxybutyl)-4-thio-alpha -D-glucopyranoside (20) and methyl 4-S-[(1,5/4,6)- and (4,6/1,5)-4-alpha-D-glucopyranosylthio-5,6-dihydroxy-2- cyclohexen-1-yl]-4 thio-alpha-D-glucopyranoside (29a/b), which are analogues of methyl alpha maltotrioside. The Ki values for alpha-amylase for these compounds were determined as were those of methyl alpha-maltotrioside and maltose. PMID- 1591773 TI - Pax in development. PMID- 1591774 TI - Retraction: Oct-3 is a maternal factor required for the first mouse embryonic division. PMID- 1591775 TI - c-abl has a sequence-specific enhancer binding activity. AB - The enhancers of several distinct viruses contain a common functional element, termed EP. This element binds ubiquitous cellular proteins and generates specific complexes in gel retardation analysis. Ultraviolet cross-linking and Southwestern analysis showed that a 140 kd polypeptide is the major EP DNA-binding protein. Using a combination of DNA binding and immunological techniques, we have identified the c-abl protein in a nuclear complex that binds to the EP element. abl was found to have both a specific and high affinity DNA binding activity. The ability to bind DNA is abolished in the mutant abl protein, p210bcr-abl, consistent with its cytoplasmic localization in chronic myelogenous leukemia. PMID- 1591776 TI - Nucleoplasmin remodels sperm chromatin in Xenopus egg extracts. AB - Nucleoplasmin is necessary and sufficient for the initial stage of Xenopus sperm decondensation in egg extracts. In this article we show that sperm decondensation is accompanied by loss of two sperm-specific basic proteins (X and Y) and gain of histones H2A and H2B, resulting in nucleosome formation. Purified nucleoplasmin alone removes X and Y and assembles purified H2A and H2B on decondensing sperm chromatin, forming nucleosome cores. Immunodepletion of nucleoplasmin from extract prevents removal of X and Y and addition of H2A and H2B, while adding back nucleoplasmin restores decondensation and X and Y removal. Thus, nucleoplasmin acts as both an assembly and a disassembly factor for remodeling sperm chromatin at fertilization. PMID- 1591777 TI - Cis-acting sequences regulating expression of the human alpha-globin cluster lie within constitutively open chromatin. AB - Current models suggest that tissue-specific genes are arranged in discrete, independently controlled segments of chromatin referred to as regulatory domains. Transition from a closed to open chromatin structure may be an important step in the regulation of gene expression. To determine whether the human alpha-globin cluster, like the beta-globin cluster, lies within a discrete, erythroid-specific domain, we have examined the long-range genomic organization and chromatin structure around this region. The alpha genes lie adjacent to at least four widely expressed genes. The major alpha-globin regulatory element lies 40 kb away from the cluster within an intron of one of these genes. Therefore, unlike the beta cluster, cis-acting sequences controlling alpha gene expression are dispersed within a region of chromatin that is open in both erythroid and nonerythroid cells. This implies a difference in the hierarchical control of alpha- and beta-globin expression. PMID- 1591778 TI - Activation of c-src neuron-specific splicing by an unusual RNA element in vivo and in vitro. AB - A conserved positive-acting RNA sequence was found to be required for the neuron specific splicing of the mouse c-src N1 exon. The sequence lies in the intron between exons N1 and 4, close to the N1 donor site. Normally, only the neural specific splicing of exon N1 required this sequence. When the intron downstream of N1 was shortened, splicing at the constitutive exon 4 acceptor also became dependent on the activating sequence. The neuronal and nonneuronal patterns of src splicing were reconstituted in vitro. HeLa cell extracts spliced exon 4 to exon 3, skipping exon N1. Weri-1 retinoblastoma cell extracts spliced exon 4 to exon N1 as well as to exon 3. Both patterns of splicing were dependent on the activating sequence. A 123 nt RNA containing just the activating sequence specifically inhibited both patterns of src splicing, indicating that factors bound to the activator were required for its effects. PMID- 1591779 TI - A critical role of lambda 5 protein in B cell development. AB - The lambda 5 gene is a homolog of immunoglobulin J lambda-C lambda genes, expressed specifically in immature B-lineage cells. Lambda 5-encoded molecules form membrane complexes with mu or D mu proteins in association with an additional protein specifically expressed in immature B cells that is encoded by the Vpre-B gene. We have generated mice in which the lambda 5 gene is inactivated by targeted gene disruption in embryonic stem cells. In these mice, B cell development in the bone marrow is blocked at the pre-B cell stage. However, the blockade is leaky, allowing B cells to populate the peripheral immune system at a low rate. These cells are allelically excluded and able to respond to antigen. PMID- 1591780 TI - Mechanism of C. trachomatis attachment to eukaryotic host cells. AB - A novel trimolecular mechanism of microbial attachment to mammalian host cells was characterized for the obligate intracellular pathogen Chlamydia trachomatis. Using purified glycosaminoglycans (GAGs) and specific GAG lyases, we demonstrated that a heparan sulfate-like GAG present on the surface of chlamydia organisms is required for attachment to host cells. These observations were supported by inhibition of attachment following binding of heparan sulfate receptor analogs to chlamydiae and by demonstrating that chlamydiae synthesize a unique heparan sulfate-like GAG. Furthermore, exogenous heparan sulfate, as an adhesin analog, restored attachment and infectivity to organisms that had lost these attributes following treatment with heparan sulfate lyase. These data suggest that a GAG adhesin ligand mediates attachment by bridging mutual GAG receptors on the host cell surface and on the chlamydial outer membrane surface. PMID- 1591782 TI - A novel transcription factor reveals a functional link between the RNA polymerase II CTD and TFIID. AB - The RNA polymerase II large subunit carboxy-terminal domain (CTD) plays a role in transcription initiation, but its mechanism of action is not well understood. We have investigated the function of the SRB2 gene, which was isolated as a dominant suppressor of CTD truncation mutations. The allele specificity of this suppressor indicates that SRB2 and the CTD are involved in the same function. Indeed, cells lacking SRB2 and cells lacking a large portion of the CTD exhibit the same set of conditional growth phenotypes and exhibit very similar defects in gene expression in vivo. The SRB2 protein is a novel transcription factor that has an important role in basal and activated transcription in vitro and is essential for efficient establishment of the transcription initiation apparatus. Template commitment experiments suggest that SRB2 becomes physically associated with the transcription initiation complex. We find that SRB2 binds specifically to TFIID. As SRB2 and the RNA polymerase II CTD are involved in the same function, these results reveal a functional link between the CTD and the TATA-binding factor. This study implicates the CTD in recruitment of RNA polymerase II to the transcription initiation complex. PMID- 1591783 TI - Medical problems. PMID- 1591781 TI - Specific interaction between the nonphosphorylated form of RNA polymerase II and the TATA-binding protein. AB - Fractionation of a transcription-competent HeLa cell extract on a column containing one copy of the heptamer repeat (YSPTSPS) present in the carboxy terminal domain (CTD) of the largest subunit of RNA polymerase II resulted in the loss of transcriptional activity. Fractionation of the extracts on columns containing mutations of the heptamer repeat was without effect. Such transcriptionally inactive extracts regained their ability to specifically transcribe different class II promoters upon the addition of human TFIID, recombinant yeast TATA-binding protein (TBP), or proteins bound to the column. Fractionation of RNA polymerase II on columns containing human or yeast TBP resulted in the specific retention of the nonphosphorylated form of RNA polymerase II. The phosphorylated form of the enzyme was unable to interact with TBP. The specific interaction of RNA polymerase II with TBP was mediated by the CTD of RNA polymerase II. PMID- 1591784 TI - Athletic heart syndrome. AB - AHS is a benign condition consisting of physiologic adaptations to the increased cardiac work load of exercise. Its primary features are biventricular hypertrophy and bradycardia associated with normal systolic and diastolic function. In addition, the alterations in cardiac structure are related to the type of training with dynamic training causing proportionally greater dilation and static training primarily increased wall thickness. AHS is associated with abnormalities in ECG, radiograph, and echocardiographic findings. It is important to be aware of these changes so that they are not misinterpreted to represent pathologic states. In particular, the distinction between AHS and HCM can be difficult, although certain historic and echocardiographic features can help differentiate the two. PMID- 1591785 TI - Sudden death. AB - Sudden death in athletes is a tragic, but fortunately infrequent, event. In young athletes (30 years old and younger) structural cardiovascular disease, often congenital, is usually responsible. Athletes over 30 years old who die suddenly are most frequently found to have severe atherosclerotic coronary artery disease. This article discusses the type of cardiovascular diseases underlying sudden death in athletes and approaches to preventing these tragedies. PMID- 1591786 TI - Exercise and the hypertensive athlete. AB - Exercise helps to manage high blood pressure in most circumstances and should be encouraged in both hypertensive athletes and active individuals with this disease. Many physiologic mechanisms have been proposed that explain this benefit. Presently, it appears from both human and animal studies that exercise of moderate intensity may be optimal for control of high blood pressure. Exercise testing for the future prediction of hypertension is an intriguing concept, but more data needs to be gathered before screening can be recommended. PMID- 1591787 TI - Exercise-induced anaphylaxis and urticaria. AB - Physical exercise is a stimulus capable of provoking urticaria and anaphylaxis in certain individuals. The cutaneous manifestations of EIA include erythema, pruritus, and urticarial whealing. Symptoms may also progress to angioedema, laryngeal edema, bronchospasm, and hypotension. Attacks are consistently associated with increases in serum histamine levels, and atopic individuals are more commonly affected. At least two distinct diseases cause EIA, including CU and classic EIA. A variant form of EIA may also exist. CU episodes are induced by increases in body temperature occurring secondary to physical exercise or passive body warming. Classic EIA episodes are induced only by exercise. Further differences between these two disorders include the size of skin lesions and the high frequency of progression to upper airway distress and shock in classic EIA. The manifestations of EIA occur as a result of mast cell degranulation that releases histamine and other mediators into the circulation. An exaggerated cholinergic response to body warming seems to provoke mast cell degranulation in individuals with CU. In classic EIA, exercise acts as a physical stimulus, which through an unknown mechanism provokes mast cell degranulation. The treatment of acute episodes of EIA includes administration of epinephrine and antihistamines, airway maintenance, and cardiovascular support. Prophylactic treatment includes exercise avoidance, abstention from coprecipitating foods and medications, pretreatment with antihistamines and cromolyn, and the induction of tolerance through regular exercise. PMID- 1591788 TI - Sports anemia. AB - It is apparent that exercise can influence erythropoiesis and red cell survival in a variety of fascinating ways. A number of mechanisms have been reviewed that could lead to mild changes in the Hb or red cell mean corpuscular volume. In addition, athletes may be at high-risk to develop decreased iron stores. Nevertheless, iron deficiency anemia is uncommon and the ritual of routine iron supplementation is not recommended. Clearly, most of the mechanisms discussed lead to only subtle changes in the overall red cell numbers and indices. Yet there is a small subset of athletes who will have red cell changes that can only be attributable to participation in sports. The diagnosis of sports anemia, however, remains one of exclusion. PMID- 1591789 TI - Depression and chronic fatigue in athletes. AB - For the most part, the competitive athlete is a well-adjusted individual who demonstrates considerable vigor and well-being, as well as less depression, anxiety, and fatigue than nonathletic counterparts. The well-trained athlete, however, may also have a personality that is somewhat rigid, strongly goal oriented, and perfectionist. It is not unrealistic to expect that when confronted with diminished performance or success, such an athlete may be compelled to drive himself or herself harder to succeed. Such behavior typically leads to the phenomenon of overtraining, which can express itself in the form of chronic fatigue and depression. There are a number of other organic causes of chronic fatigue and depression, however, which must be excluded by careful evaluation and appropriate diagnostic testing. Although the evaluation of the athlete who presents with chronic fatigue and depression can be somewhat complex, a diagnostic framework has been outlined here to assist the clinician in the assessment of an athlete who presents with such complaints. PMID- 1591790 TI - Headaches in the athlete. AB - Headache is one of the most common entities to affect mankind. In addition to headaches seen in the general population, there are numerous types of headaches that are related to physical activity and sports. This article discusses the mechanism, presentation, evaluation, treatment, and prevention of the most common causes of headache in the athlete. PMID- 1591791 TI - Exercise-associated amenorrhea. AB - Currently, more is unknown than is known about the complex interactions of exercise and the female reproductive system. Three types of menstrual changes are observed in athletes: luteal phase deficiency, anovulation, and exercise associated amenorrhea. This article presents a clinically oriented update on the hypothesized causes, evaluation, and management of menstrual changes in active women. PMID- 1591792 TI - Exercise and pregnancy. AB - Despite the theoretic risks to both mother and fetus listed in this article, exercise in pregnancy conducted in moderation appears to be safe in most cases. The current published literature includes the following consistent findings: 1. Women who exercised before pregnancy and continued to do so during pregnancy tended to weigh less, gain less weight, and deliver smaller babies than controls. 2. All women, regardless of initial level of physical activity, decrease their activity as pregnancy progresses. 3. No information is available to assess whether active women have better pregnancy outcome than their sedentary counterparts. No information is available on sedentary women. 4. Physically active women appear to tolerate labor pain better. 5. Exercise can be used as an alternative and safe therapeutic approach for gestational diabetes. Pregnancy should not be a state of confinement, and cardiovascular and muscular fitness can be reasonably maintained. Restriction of physical activity should be dictated by obstetric and medical indications only. Health care providers should inform pregnant women of potential risks and individualized exercise prescription as indicated and necessary. PMID- 1591793 TI - Diabetes mellitus and exercise. AB - Physical exercise is traditionally considered beneficial in the treatment of IDDM. Attainment and maintenance of ideal body weight, improvement in self-image, and decreases in hypertension and lipid-related cardiovascular risk factors can all be achieved by the diabetic patient who exercises. Although the value of exercise in improving long-term glycemic control remains controversial, athletic participation by individuals with IDDM is encouraged to achieve the same health benefits enjoyed by exercising nondiabetic individuals. Knowledge of the metabolic responses to exercise in IDDM patients is required for appropriate guidance and management. Careful monitoring and adjustment of insulin doses and nutrition plans can then make possible the safe and successful participation of IDDM patients in virtually any athletic activity. PMID- 1591794 TI - Environmental and thermal injury. AB - The environment can have a profound impact on human performance. Over the past decade there has been considerable interest in the scientific study of the human ability of to protect oneself against heat and cold. This new knowledge has led to a better understanding of physiology and resulted in better prevention, recognition, and treatment of hyperthermia, hypothermia, and frostbite. This article reviews the pathophysiology of extreme environmental exposure and discusses current strategies for prevention and treatment. PMID- 1591795 TI - Renal complications of exercise. AB - Exercise-related conditions such as proteinuria and hematuria are relatively common and represent diagnoses of exclusion. A variety of renal disorders with identical presenting signs and symptoms must be excluded as underlying disorders. The relationship of the onset to and clearance after exercise of the findings is key to making the diagnosis of these exercise-related conditions. Athletes with sports hematuria or proteinuria are not prone to develop renal disease but must be followed closely to exclude the development of a significant underlying problem. Fortunately, acute renal failure is a rare and preventable life threatening complication of exercise. Appropriate training techniques and adequate fluid replacement are key in prevention, as are prompt recognition and treatment of dehydration and disorders of thermoregulation. Prevention and prompt recognition are also the first steps in the approach to renal trauma. Close observation and conservative management of the athlete with renal trauma will result in salvaging more kidneys. PMID- 1591796 TI - Gastrointestinal disorders in the athlete. AB - This article presents an overview of some of the more commonly encountered disorders of the gastrointestinal tract that are seen in athletes. As with other medical conditions, the clinician can often be blinded by an athlete's physical activity and overlook underlying disease. Fortunately, most of the maladies described here are amenable to medical treatment, and with proper diagnosis and management the athlete should be able to achieve his or her maximal athletic performance. The study of the gastrointestinal tract and exercise is still in its early stages and was prompted by the need to explain clinical observations. Although some questions have been answered, the positive and negative effects of physical activity on the gastrointestinal tract have many avenues of research left to explore. PMID- 1591797 TI - The relationship of osteoarthritis and exercise. AB - We have discussed the epidemiology of osteoarthritis as well as its physiology and pathophysiology. Most important, we have looked at exercise as a potential cause of this chronic disease and have offered information concerning the possibility of SROA. Finally, we have looked at exercise as a possible treatment and how it may become an intervention and positive factor in the reversibility of this disease. Figure 4 summarizes our current knowledge of the relationship between exercise and the chronic disease process known as osteoarthritis. PMID- 1591798 TI - [Reliability of the Czech version of the GBS rating scale for dementia syndromes]. AB - By the geriatric evaluation scale GBS for syndromes of dementia in a Czech translation 31 patients of the gerontopsychiatric department were evaluated. The reliability study was implemented by two psychiatrists. The authors compared the results of their own study with results of studies made in other countries. They found a high grade of reliability of the evaluation. They consider the definition of items on the scale and their evaluation practical and suited even for less trained observers or observers with a different training. PMID- 1591799 TI - [Characteristics of favorable and poor development of health services and social conditions for the aged]. AB - Two stage probability samples were selected to represent the populations resident in one metropolitan (Prague-1 n = 484) and one country (Opava n = 538) geographical and administrative district. The index cases were contacted and surveyed in a field study. Data were collected by means of standardized interviews by nurses and social workers and complemented from GP's case notes, if available. A significant proportion of cases had no contact with health services at all. Both samples were followed-up for three years. The description of cases was condensed into 27 meaningful variables assessing social, health and living characteristics at the time of the beginning of the study. 11 follow-up course and outcome criteria were derived from the follow-up data in a similar way. Results of the metropolitan and country sample comparison of social and health care needs of five age groups, and of multivariate analysis of predictive relation between the initial characteristics and development and outcome criteria dependent variables are presented and discussed. PMID- 1591800 TI - [Adaptation disorders in the aged after admission to a home for the aged]. AB - The author investigates by means of the GBS scale the influence of a new environment in old age pensioners homes on the adaptation process of old people and draws attention to the problem of adaptation during the first six months after admission to the home. He tries to prove the essential length of time needed for adaptation. The author deals also with dynamic changes on mental manifestations of old people during the first six months in the old age pensioners home and those spheres of the psyche where the most marked variations occur. He follows up factors which participate in the process of adaptation and deals with the problem whether life in an old age pensioners home in an advantage for old people and a solution of the problem of old age. He tries to create a simple method of investigation of the adaptation process which can be used in common practice. PMID- 1591801 TI - [Use of the MSE scale in geriatric psychiatry]. AB - In preliminary research the authors tested the congruent validity of MSE by comparison with results of the MMSE scale which previously proved useful. In 155 probands of senior age they used MSE, WAIS-R. They found a close correlation of the MSE score and the results. of psychomotor examination of the intellect and memory. As regards different factors of the intellect the MSE performance correlated most closely with the social intelligence and practical instructive solution of problems. The scale has a satisfactory sensitivity but low specificity. The score is influenced by the promorbid intelligence, education and age. MSE differentiates clinically demented and not demented patients and patients with endogenous depression from dementia. The differences between groups of dementia with a different aetiology--multiinfarction and dementia of Alzheimer's type--were not statistically significant. PMID- 1591802 TI - [Electroconvulsive therapy in the Czech Republic 1981-1989]. AB - The authors processed statistical data on the application of electroconvulsive treatment in 1981-1989 in all in-patient psychiatric departments in the Czech Republic. During this period a slight decline of shocked subjects was recorded. Among shocked patients there is a permanent, higher relative ratio of women. Approximately every 18th discharged or deceased patient underwent electroconvulsive treatment. Psychiatric hospital departments use electroconvulsive treatment to a very different extent. Most frequently patients with the diagnosis of schizophrenic psychosis (43%), affective psychosis (36%) and other inorganic psychoses (8%) receive shock therapy. PMID- 1591803 TI - [Psychoanalysis in the diagnosis and therapy of anorexia nervosa in adolescence]. PMID- 1591804 TI - [Monitoring urinary levels of chlorpromazine and thioridazine in patients]. PMID- 1591806 TI - [Development of psychotherapy in the USA]. PMID- 1591805 TI - [20 years' of the psychotherapy department in Kromeriz]. PMID- 1591807 TI - [A promise given to children]. PMID- 1591808 TI - [The effect of reduced doses of BCG vaccine on the occurrence of osseous complications after vaccination]. AB - The authors present a review on the incidence of osseous complications after calmettization with the Soviet BCG vaccine during the period from February 1, 1980 and June 30, 1985 when the total dose of the vaccine was used, as compared with the period from July 1, 1985 to December 31, 1989 when the dose of the vaccine was reduced to half. During the first period 28 cases of the disease were recorded (on average 5 cases in every year of birth) which was an incidence of 3.71/100,000 vaccinated children. After reduction of the vaccine dose to half another 11 cases of the disease were recorded, i.e. a reduction of the incidence to 2.30/100,000 vaccinated children. During the last two years of this period only one case in each vaccinated birth year was notified. A major part of the children with bone complications after calmettization was vaccinated with a batch of vaccine which contained a higher number of germs, close to the upper range of normal values. In the development of these complications thus, no doubt, among other factors also the dose of vaccine participates. As bone complications occur after calmettization even after reduction of the dose of vaccine to half, though the incidence was lower, is should be considered whether the hitherto used dose used for vaccination of neonates is not too high. PMID- 1591809 TI - [Treatment of neonates with extracorporeal membrane oxygenation]. AB - ECMO is a therapeutic method which markedly improved the prognosis of premature or near term infants with severe cardiorespiratory insufficiency where conventional intensive care, incl. pulmonary ventilation and medicamentous support of the circulation did not help. It is method which needs the necessary technical equipment, perfect laboratory facilities and well trained teamwork. It is associated with risks which are not negligible, clearly defined indications as well as contraindications. The programme of ECMO, when introduced, should be regional and departments which use it should be in the area of large university hospitals. Despite the considerable costs associated with establishment of a therapeutic ECMO unit, it pays, as in the most threatened group of neonates it shortens the period these infants spend at the intensive care unit and reduces their mortality rate and severe forms of late postasphyctic morbidity. PMID- 1591810 TI - [Exercise-induced airway obstruction in asthmatic children and adolescents]. AB - In 115 asymptomatic asthmatic children and adolescents (age 6-18 years) there was studied the magnitude of airway obstruction, induced by various physical efforts and assessed from the recording of maximum expiratory flow-volume curves and in some patients by "specific" airway conductance measurement in a body plethysmograph. The effects of 5 minutes free running outdoors, 5 minutes of exercise on a bicycle ergometer (2 watts/kg of body weight), routine swimming training in swimming pool and of forced expiration maneuver on the magnitude of airway obstruction were assessed. The most frequent and largest degree of airway obstruction was observed after 5 min. free running outdoors (heart rate after running 160-200/min). The obstruction was revealed in 80-100% asthmatics in various groups. The chosen lung function parameters showed exercise-induced airway obstruction in the same patients in various proportions as well as the magnitude of the obstruction. Following free running outdoors the values of maximum expiratory flow at 25% of vital capacity and "specific" airway conductance were most reduced. Spontaneous retreat of obstruction was observed in the course of 2 hours. The physical exercise on a bicycle ergometer was a small stimulus in inducing of airway obstruction. The swimming in a pool did not provoke any obstruction. In 10% of our asthmatics airway obstruction was observed following forced expiration maneuver. Airway obstruction induced by 5 minutes free running outdoors and assessed best by flow-volume curves appeared as a suitable test in the assessment of airway hyperresponsiveness. PMID- 1591811 TI - [Somatic development of Czech and Slovak children and adolescents in the 80s]. AB - The paper introduces the new growth values of body height and body weight of the Czech and Slovak children and youth aging 1 1/2 to 18 years. The research was carry out during the 1987-1988 years on the whole territory of Czech and Slovak Federative Republic. It embraceds 47,099 probands. In comparison with the oldest and more new czech and slovak values the both characteristics in interpretation of long-termed and short-termed action of secular trend is percetible the further enlargement of the body height and body weight. In contrast to ancient is perceptible that the Slovak children in the present time are equal or higher from the Czech children. During the period of adolescence they are however exceed from the Czech probands. The like relation exists by the boys in the body weight. However, the Slovak girls are in mean lighter than the Czech girls already from 9 years of age. The counterpoise of body weight and eventual exceeding of Czech children theirs Slovak contemporaries can be possible originates with improve nutritional conditions of the Slovak populations in the antecendent periods after the Second World War. The mean intersexual differences on the end of adolescent period by both of our nationalities are 11-12 cm of body height and 12-13 kg of body weight. PMID- 1591812 TI - [Dialysis therapy in children and adolescents]. PMID- 1591813 TI - [Mucocutaneous lymph node syndrome--Kawasaki's disease]. PMID- 1591814 TI - [Struma in childhood]. PMID- 1591815 TI - [Suggestions in clinical psychology (the early years)]. PMID- 1591816 TI - [Formation of a new department for maternal, child and adolescent care at the Ministry of Health in the Czech Republic]. PMID- 1591817 TI - [The effect of drugs on gastric emptying]. PMID- 1591818 TI - [2 important anniversaries]. PMID- 1591819 TI - Basic structure-function relations of the epicardial coronary vascular tree. Basis of quantitative coronary arteriography for diffuse coronary artery disease. AB - BACKGROUND: Quantitative coronary arteriography has been validated for stenotic segments of coronary arteries. However, it does not currently account for diffuse coronary artery disease, because the normal size of the coronary artery for its distal myocardial bed size is not known and cannot be measured directly with diffuse involvement of the artery. METHODS AND RESULTS: From clinical coronary arteriograms of 12 patients without coronary artery disease (group 1) and in 17 patients with coronary artery disease (group 2), we determined by quantitative coronary arteriography 1) the relations among measured coronary artery cross sectional lumen area, summed distal branch lengths, and regional myocardial mass distal to each point in each coronary artery; 2) the ratio of coronary artery lumen area between parent and daughter vessels at 50 bifurcations; and 3) which of three different theoretical physical principles could underlie the tree structure of the human coronary artery system, by comparing the coronary artery size, branch lengths, regional mass, and relations between parent-to-daughter lumen area ratios with those for the different theoretical physical principles to test which principle best fit the observed data and therefore which principle most probably characterizes the human coronary artery tree structure. The results showed that 1) there is a close correlation between the lumen area of a coronary artery at each point along its length and the corresponding summed distal branch lengths and regional myocardial mass in patients without and with coronary artery disease; 2) measured coronary artery lumen area in patients with coronary artery disease is diffusely 30-50% too small for distal myocardial bed size compared with normal subjects; and 3) the observed relations among coronary artery size, distal summed lengths, myocardial bed size, and parent-to-daughter size ratios are not consistent with the theoretical principle of constant mean blood flow velocity in the coronary circulation but are consistent with the principles of minimum viscous energy loss and of limited/adaptive vascular wall shear stress characterized by a 2/3 power law relating coronary artery lumen area to distal summed branch lengths and regional mass or parent-to-daughter branching ratios. CONCLUSIONS: These observations provide a basis for quantifying diffuse coronary artery disease on clinical arteriograms. PMID- 1591821 TI - Complications and mortality of percutaneous balloon mitral commissurotomy. A report from the National Heart, Lung, and Blood Institute Balloon Valvuloplasty Registry. AB - BACKGROUND: In response to the increasing use of percutaneous balloon mitral commissurotomy, the National Heart, Lung, and Blood Institute established the Balloon Valvuloplasty Registry in November 1987. METHODS AND RESULTS: Between November 1, 1987, and October 31, 1989, 738 patients aged 18 or older underwent percutaneous balloon mitral commissurotomy at the clinical sites. Data were prospectively entered into the registry at the time consent was obtained. Serious complications occurred in 87 procedures, or 12%. Death in the laboratory occurred in eight patients, or 1%. Within 30 days there were 24 cumulative deaths, 18 cardiac and six noncardiac. Univariate analysis revealed that older age, a history of cardiac arrest, cerebrovascular disease, dementia, renal insufficiency, cachexia, class IV congestive heart failure, use of an intra aortic balloon pump, use of sympathomimetic amines, and a high echo score (greater than or equal to 13) were associated with early death (p less than 0.01). Additional univariate predictors included a precommissurotomy mitral valve area of less than 0.7 cm2. Left atrial pressure greater than 12 mm Hg and a mitral valve area of less than 1.5 cm2 after the procedure were also associated with higher 30-day mortality (p less than 0.05). Multivariate analysis identified higher echo score and smaller valve area before the procedure as the strongest predictors of early death (p less than 0.001). Centers that performed more than 25 procedures also had lower complication rates. CONCLUSIONS: Although percutaneous balloon mitral commissurotomy appears to be effective at relieving the hemodynamic effects of rheumatic mitral stenosis, it does have risks. In properly selected patients, however, it appears to have low morbidity and 30-day mortality. Individual center experience with the procedure also appears to have great impact on complications. PMID- 1591820 TI - ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. AB - BACKGROUND: In humans, angiotensin converting enzyme (ACE) inhibition attenuates the vasoconstriction induced by sympathetic stimulation in a number of peripheral districts. Whether this is also the case in the coronary circulation is unknown, however. METHODS AND RESULTS: In nine normotensive patients with angiographically assessed coronary atherosclerosis, we measured the changes in mean arterial pressure (intra-arterial catheter), heart rate, rate-pressure product (RPP), coronary sinus blood flow (CBF, thermodilution method), and coronary vascular resistance (CVR, ratio between mean arterial pressure and CBF) induced by the cold pressor test (CPT, 2 minutes) and diving (30 seconds), i.e., two stimuli eliciting a sympathetic coronary vasoconstriction. The measurements were performed in the control condition and 30 minutes after captopril 25 mg p.o. In the control condition, CPT caused an increase in mean arterial pressure and heart rate. Despite the increase in RPP (+20.7 +/- 3.2%, p less than 0.01), CBF did not change and CVR increased (+12.2 +/- 4.0%, p less than 0.05). diving caused an increase in mean arterial pressure and a reduction in heart rate. RPP increased (+14.3 +/- 3.5%, p less than 0.01), but despite this increase, there was a reduction in CBF and a marked increase in CVR (+37.3 +/- 7.4%, p less than 0.01). Captopril did not modify the blood pressure and heart rate responses to both stimuli except for a slight accentuation of the bradycardia to diving. Despite the unchanged or only slightly reduced RPP response, the increase in CVR was markedly and significantly attenuated (p less than 0.01). CONCLUSIONS: ACE inhibition attenuates sympathetic coronary vasoconstriction in patients with coronary artery disease. This is probably due to removal of the facilitating influence of angiotensin II on sympathetic modulation of coronary vasomotor tone. PMID- 1591822 TI - Hypolipidemic effect of type Ia antiarrhythmic agents in postinfarction patients. AB - BACKGROUND: Elevated levels of cholesterol and apoprotein B (apo B), the essential carrier protein for low density lipoprotein, are major lipid risk factors for premature coronary disease. Antiarrhythmic agents are frequently prescribed to patients with coronary heart disease and associated cardiac arrhythmias. As part of another study, we retrospectively investigated the effect of antiarrhythmic agents on blood lipids. METHODS AND RESULTS: The study population consisted of 1,567 postinfarction patients on whom we prospectively collected serial blood samples for lipid and apoprotein determinations and recorded the concomitant medications the patients were receiving at three follow up time periods. The lipids, analyzed at a central core laboratory, included total cholesterol, triglycerides, high density lipoprotein cholesterol (HDL C), and apoproteins A-I (apo A-I), A-II (apo A-II), and apo B. The difference in the group mean lipid values for patients receiving and not receiving type Ia antiarrhythmic agents (quinidine, procainamide, and disopyramide) was evaluated by the two-sample t test, and multiple linear regression analyses were performed to adjust for relevant covariates. Patients using type Ia antiarrhythmic agents at the 30-month postinfarction contact (n = 76) had 8.6% lower cholesterol (p less than 0.003), 22.3% lower triglycerides (p less than 0.0002), 6.2% lower apo A-I (p = 0.02), 10.1% lower apo A-II (p less than 0.001), and 12.7% lower apo B (p less than 0.0001) levels than patients not on these medications (n = 1,491). These lower lipid levels were found after adjustment for age, sex, diabetes, smoking status, concomitant medications, and a variety of clinical factors relating to the severity of the coronary disease process. The HDL C levels were similar in those receiving and not receiving type Ia agents. CONCLUSIONS: Patients on type Ia antiarrhythmic agents had significantly and meaningfully lower cholesterol, triglyceride, apo A-II, and apo B levels than patients not receiving these agents. The mechanism of this hypolipidemic effect is undefined, but the mechanism may be related to an alteration by these agents of ionic membrane currents at the hepatocyte level. PMID- 1591823 TI - Spectral analysis of signal-averaged electrocardiograms in patients with idiopathic ventricular tachycardia of left ventricular origin. AB - BACKGROUND: The signal-averaged ECG has been used to detect late potentials, and it is considered a noninvasive marker for areas of slow conduction requisite for reentrant arrhythmia. Late potentials are not usually found in patients with idiopathic ventricular tachycardia (VT); nevertheless, fragmented electrograms are often recorded in those patients during endocardial mapping. The purpose of this study was to investigate the spectral content of the signal-averaged ECGs with use of fast Fourier transform analysis (FFT) in patients with idiopathic VT of left ventricular origin. METHODS AND RESULTS: Signal-averaged ECGs were recorded in 12 patients with idiopathic VT originating from the left ventricle (group 1) and 25 age-matched normal volunteers (group 2). Frequency analysis with FFT was performed with a Blackman-Harris window in a segment length of 120 msec from 40 msec before the end of the QRS complex, and the frequency spectrum was displayed in a three-dimensional graph. Area ratio 1 (area of 20-50 Hz/area of 10 50 Hz) and area ratio 2 (area of 40-100 Hz/area of 0-40 Hz) were calculated in all subjects. Late potentials defined by the time domain were negative in all subjects. The area ratios of group 1 were significantly higher than those of group 2. High-frequency components in the three-dimensional graph were confined within the QRS complex. CONCLUSIONS: These results suggest that frequency analysis of signal-averaged ECGs with FFT is an available method for detecting the high-frequency component within the QRS complex in some patients with idiopathic VT of left ventricular origin. PMID- 1591824 TI - Spectral analysis of 87-lead body surface signal-averaged ECGs in patients with previous anterior myocardial infarction as a marker of ventricular tachycardia. AB - BACKGROUND: There were few studies on the relation between the body surface distribution of high- and low-frequency components within the QRS complex and ventricular tachycardia (VT). METHODS AND RESULTS: Eighty-seven signal-averaged ECGs were obtained from 30 normal subjects (N group) and 30 patients with previous anterior myocardial infarction (MI) with VT (MI-VT[+] group, n = 10) or without VT (MI-VT[-] group, n = 20). The onset and offset of the QRS complex were determined from 87-lead root mean square values computed from the averaged (but not filtered) ECG waveforms. Fast Fourier transform analysis was performed on signal-averaged ECG. The resulting Fourier coefficients were attenuated by use of the transfer function, and then inverse transform was done with five frequency ranges (0-25, 25-40, 40-80, 80-150, and 150-250 Hz). From the QRS onset to the QRS offset, the time integration of the absolute value of reconstructed waveforms was calculated for each of the five frequency ranges. The body surface distributions of these areas were expressed as QRS area maps. The maximal values of QRS area maps were compared among the three groups. In the frequency ranges of 0-25 and 150-250 Hz, there were no significant differences in the maximal values among these three groups. Both MI groups had significantly smaller maximal values of QRS area maps in the frequency ranges of 25-40 and 40-80 Hz compared with the N group. The MI-VT(+) group had significantly smaller maximal values in the frequency ranges of 40-80 and 80-150 Hz than the MI-VT(-) group. These three groups were clearly differentiated by the maximal values of the 40-80-Hz QRS area map. CONCLUSIONS: It was suggested that the maximal value of the 40-80-Hz QRS area map was a new marker for VT after anterior MI. PMID- 1591825 TI - Role of family history in patients with myocardial infarction. An Italian case control study. GISSI-EFRIM Investigators. AB - BACKGROUND: A family history of heart disease has been reported to increase the risk of coronary heart disease. We examined the relation between family history of myocardial infarction (MI) and risk of acute MI to establish the independency of this association, the degree of risk in relation to the number and age of relatives affected, and the possible interaction between family history and other major risk factors for MI. METHODS AND RESULTS: In a case-control study conducted in Italy within the framework of the GISSI-2 Trial, 916 cases of newly diagnosed MI and 1,106 hospital controls were identified. Using a structured questionnaire, data were collected on the history of MI in first-degree relatives and the age at which the event occurred. Compared with subjects without family history of MI in first-degree relatives, the relative risk (RR) of MI was 2.0 (95% confidence interval, CI, 1.6-2.5) in those with one and 3.0 (95% CI, 2.0-4.4) in those with two or more relatives affected (chi 2(1) test for trend, 54.1; p less than 0.001). Such an increase was not substantially affected by allowance for recognized risk factors. The risk related to family history involving at least two relatives was higher for early MI (less than 55 years) (RR, 20.0; 95% CI, 3.3 121.2) compared with later MI (less than or equal to 65 years) (RR, 3.5; 95% CI, 1.8-6.6). When known risk factors were considered for their interaction with family history, the effect on RR was approximately multiplicative for several variables, including smoking, serum cholesterol, hypertension, and hyperlipidemia but not for diabetes and body mass index. Thus, the presence of both family history and smoking and cholesterol levels greater than or equal to 226 mg/dl led to an RR of 14 (95% CI, 3.7-50.0) and 8.3 (95% CI, 1.8-38.7), respectively. CONCLUSIONS: This study indicates that a family history of MI is an independent risk factor for MI, and that the number of relatives and the age at which they were affected is related to the strength of the association. There is a multiplicative effect on RR between family history and several major risk factors for MI. PMID- 1591826 TI - Heart rate variability during the acute phase of myocardial infarction. AB - BACKGROUND: After acute myocardial infarction (AMI), several abnormalities of the autonomic control to the heart have been described. Heart rate (HR) variability has been used to explore the neural control to the heart. A low HR variability count measured 7-13 days after AMI is significantly related to a poor outcome. Little information is available on HR variability early after AMI and its relation to clinical and hemodynamic data. METHODS AND RESULTS: We studied 54 consecutive patients (42 men and 12 women; mean age, 60.4 +/- 11 years) with evidence of AMI by collecting the 24-hour HR SD from Holter tapes recorded on day 2 or 3. We also measured HR variability in 15 patients with unstable angina and in 35 age-matched normal subjects. HR variability was lower in AMI than in unstable angina patients (57.6 +/- 21.3 versus 92 +/- 19 msec; p less than 0.001) and controls (105 +/- 12 msec; p less than 0.001). Also, HR variability was greater in non-Q-wave than in Q-wave AMI (p less than 0.0001) and in recombinant tissue-type plasminogen activator-treated patients with respect to the rest of the group (p less than 0.02). No difference was found for infarct site. HR variability was significantly related to mean 24-hour HR, peak creatine kinase MB, and left ventricular ejection fraction (all p less than 0.0001). Patients belonging to Killip class greater than I or who required the use of diuretics or digitalis had lower counts (p less than 0.004, p less than 0.001, and p less than 0.024, respectively). Six patients died within 20 days after admission to the hospital. In these patients, HR variability was lower than in survivors (31.2 +/- 12 versus 60.9 +/- 20 msec; p less than 0.001), and a value less than 50 msec was significantly associated with mortality (p less than 0.025). CONCLUSIONS: HR variability during the early phase of AMI is decreased and is significantly related to clinical and hemodynamic indexes of severity. The causes for the observed changes in HR variability during AMI may be reduced vagal and/or increased sympathetic outflow to the heart. It is suggested that early measurements of HR variability during AMI may offer important clinical information and contribute to the early risk stratification of patients. PMID- 1591827 TI - Functional significance of collateral blood flow in patients with recent acute myocardial infarction. A study using myocardial contrast echocardiography. AB - BACKGROUND: We hypothesized that myocardial contrast echocardiography (MCE) can be used to both measure collateral blood flow as well as assess the functional significance of collaterals in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: MCE was performed in 33 patients with recent AMI (12 +/- 7 days) and an occluded infarct-related artery (IRA), both before and after attempted percutaneous transluminal coronary angioplasty (PTCA). The size of the occluded bed was defined in patients with successful PTCA by injecting contrast directly into the opened IRA and expressed as a percent of the myocardium in the short-axis view. The percent of the perfusion bed supplied by collaterals before PTCA was determined. Transit rates of the microbubbles within the collateralized regions were also measured and were expressed as a percent of the transit rates in the normal adjacent beds. Regional function within the occluded bed was assessed using echocardiography and was graded as 1 (normal) to 5 (dyskinetic). Collaterals were graded on coronary angiography as 0 (none) to 3 (abundant). The perfusion bed size was larger for the left anterior descending (LAD) than for the right (RCA) and left circumflex (LCx) coronary arteries (37 +/- 6% versus 27 +/- 12% of the myocardium, p = 0.02). The percent of the occluded bed supplied by collateral flow was greater for RCA and LCx compared with the LAD (87 +/- 30% versus 72 +/- 22%, p less than 0.01). There was poor correlation between MCE defined percent of occluded bed supplied by collaterals and angiographic collateral grade (r = 0.13). Regions supplied by collaterals were less likely to show confluent hypoperfused zones after reperfusion compared with those not supplied by collaterals. Similarly, the percent of myocardium not perfused by either anterograde or collateral flow correlated well (r = 0.67, p less than 0.01) with peak creatine kinase levels and was more likely to be associated with Q waves. Finally, although there was poor correlation between angiographic collaterals and regional function (r = 0.20), there was a significant negative correlation between MCE-defined spatial extent of collateral flow and regional function (r = -0.57, p less than 0.01). CONCLUSION: MCE can be used to measure collateral flow in patients with recent AMI and to assess the functional significance of collaterals in these patients. This technique may be ideally suited for the assessment of collateral perfusion in patients undergoing cardiac catheterization. PMID- 1591828 TI - A randomized trial of late reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction-6 Study Group. AB - BACKGROUND: Experimental and observational clinical studies of acute coronary occlusion have suggested that late reperfusion prevents infarct expansion and facilitates myocardial healing. The purpose of this trial was to assess whether infarct vessel patency could be achieved in late-entry patients and what benefit, if any, can be demonstrated. METHODS AND RESULTS: In a double-blind fashion, 197 patients with 6 to 24 hours of symptoms and ECG ST elevation were randomly assigned to tissue-type plasminogen activator (100 mg over 2 hours) or placebo. Coronary angiography within 24 hours was used to determine infarct vessel patency status. Patients with infarct-related occluded arteries were then eligible for a second randomization to either angioplasty (34 patients) or no angioplasty (37 patients). Ventricular function and cavity size were reassessed at 1 month by gated blood pool scintigraphy and at 6 months by repeat cardiac catheterization. The primary end point, infarct vessel patency, was 65% for plasminogen activator patients compared with 27% in the placebo group (p less than 0.0001). There were no differences between these groups in ejection fraction or infarct zone regional wall motion at 1 or 6 months. At 6 months, infarct vessel patency was 59% in both groups. In the placebo group, there was a significant increase in end-diastolic volume from acute phase of 127 ml to 159 ml at 6-month follow-up (p = 0.006) but no increase in cavity size for the plasminogen activator group patients. Coronary angioplasty was associated with an initial 81% recanalization success and improved ventricular function at 1 month, but by late follow-up no advantage could be demonstrated for this procedure, and there was a 38% spontaneous recanalization rate in the patients assigned to no angioplasty. CONCLUSIONS: The study demonstrates that it is possible to achieve infarct vessel recanalization in the majority of late-entry patients with either thrombolytic therapy or angioplasty. Thrombolytic intervention had a favorable effect on prevention of cavity dilatation and left ventricular remodeling, but there are no late benefits on systolic function after thrombolysis or coronary angioplasty. The conclusions concerning overall potential benefit of applying late reperfusion therapy will require data from large-scale trials designed to assess mortality reduction. PMID- 1591829 TI - Early mortality of acute myocardial infarction in patients with and without prior coronary revascularization surgery. A Coronary Artery Surgery Study Registry Study. AB - BACKGROUND: The Coronary Artery Surgery Study (CASS) Registry is used to evaluate the effect of various baseline clinical and angiographic factors on mortality after acute out-of-hospital myocardial infarction (MI) in patients with and without prior coronary bypass surgery. METHODS AND RESULTS: Among the CASS Registry patients, there were 985 medical and 369 surgical patients who had an MI out of the hospital within 3 years after enrollment. In the medical group, 20% died before hospitalization. Medical patients with baseline three-vessel disease or left ventricular (LV) dysfunction were at high risk of immediate death. For medical patients who were hospitalized with MI, mortality was higher for older patients and those with severe angina as well as for those with extensive disease and LV dysfunction. The total 30-day mortality for medical patients was 36%. In the surgical group, 12% died before hospitalization. Surgical patients with LV dysfunction or prior MI were at highest risk of immediate death. For surgical patients hospitalized with MI, mortality was significantly increased only for patients with baseline LV dysfunction. Mortality was not significantly higher for surgical patients with multivessel disease. The total 30-day mortality for surgical patients was 21%. The prior use of aspirin or beta-blockers was not associated with reduced mortality from subsequent MI for either medical or surgical patients. Although the prevalence of cigarette smoking was high among patients who had an MI, cigarette smoking did not alter the infarct-related mortality rate. CONCLUSIONS: The surgical group had lower mortality rates than the medical group both immediately (p = 0.001), after hospitalization (p less than 0.0001), and at 30 days (p less than 0.0001). PMID- 1591830 TI - Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group. AB - BACKGROUND: A prospective regional study was conducted to identify factors associated with in-hospital mortality among patients undergoing isolated coronary artery bypass graft surgery (CABG). A prediction rule was developed and validated based on the data collected. METHODS AND RESULTS: Data from 3,055 patients were collected from five clinical centers between July 1, 1987, and April 15, 1989. Logistic regression analysis was used to predict the risk of in-hospital mortality. A prediction rule was developed on a training set of data and validated on an independent test set. The metric used to assess the performance of the prediction rule was the area under the relative operating characteristic (ROC) curve. Variables used to construct the regression model of in-hospital mortality included age, sex, body surface area, presence of comorbid disease, history of CABG, left ventricular end-diastolic pressure, ejection fraction score, and priority of surgery. The model significantly predicted the occurrence of in-hospital mortality. The area under the ROC curve obtained from the training set of data was 0.74 (perfect, 1.0). The prediction rule performed well when used on a test set of data (area, 0.76). The correlation between observed and expected numbers of deaths was 0.99. CONCLUSIONS: The prediction rule described in this report was developed using regional data, uses only eight variables, has good performance characteristics, and is easily available to clinicians with access to a microcomputer or programmable calculator. This validated multivariate prediction rule would be useful both to calculate the risk of mortality for an individual patient and to contrast observed and expected mortality rates for an institution or a particular clinician. PMID- 1591831 TI - Controlled trial of physical training in chronic heart failure. Exercise performance, hemodynamics, ventilation, and autonomic function. AB - BACKGROUND: Many secondary abnormalities in chronic heart failure (CHF) may reflect physical deconditioning. There has been no prospective, controlled study of the effects of physical training on hemodynamics and autonomic function in CHF. METHODS AND RESULTS: In a controlled crossover trial of 8 weeks of exercise training, 17 men with stable moderate to severe CHF (age, 61.8 +/- 1.5 years; left ventricular ejection fraction, 19.6 +/- 2.3%), increased exercise tolerance (13.9 +/- 1.0 to 16.5 +/- 1.0 minutes, p less than 0.001), and peak oxygen uptake (13.2 +/- 0.9 to 15.6 +/- 1.0 ml/kg/min, p less than 0.01) significantly compared with controls. Training increased cardiac output at submaximal (5.9-6.7 l/min, p less than 0.05) and peak exercise (6.3-7.1 l/min, p less than 0.05), with a significant reduction in systemic vascular resistance. Training reduced minute ventilation and the slope relating minute ventilation to carbon dioxide production (-10.5%, p less than 0.05). Sympathovagal balance was altered by physical training when assessed by three methods: 1) RR variability (+19.2%, p less than 0.05); 2) autoregressive power spectral analysis of the resting ECG divided into low-frequency (-21.2%, p less than 0.01) and high-frequency (+51.3%, p less than 0.05) components; and 3) whole-body radiolabeled norepinephrine spillover (-16%, p less than 0.05). These measurements all showed a significant shift away from sympathetic toward enhanced vagal activity after training. CONCLUSIONS: Carefully selected patients with moderate to severe CHF can achieve significant, worthwhile improvements with exercise training. Physical deconditioning may be partly responsible for some of the associated abnormalities and exercise limitation of CHF, including abnormalities in autonomic balance. PMID- 1591832 TI - Investigation of a hemodynamic basis for syncope in hypertrophic cardiomyopathy. Use of a head-up tilt test. AB - BACKGROUND: Syncope and sudden death in hypertrophic cardiomyopathy may have a hemodynamic basis. The presence of a small ventricular cavity with high intracavity pressures may activate left ventricular baroreceptors and cause reflex hypotension as described in other populations with syncope. METHODS AND RESULTS: To investigate this potential mechanism of syncope in hypertrophic cardiomyopathy, we studied 17 patients with a history of syncope (syncopal), 19 without syncope (nonsyncopal), and nine normal control subjects by using a head up tilt test. Head-up tilt at 60 degrees for 45 minutes was followed by 10-minute tilts during incremental doses of isoprenaline. Heart rate, blood pressure, and two-dimensional and Doppler echocardiography were monitored throughout. On tilting, hypertrophic cardiomyopathy patients showed a decline in mean arterial pressure of -5 +/- 6 mm Hg (p less than 0.001) compared with no change in control subjects (0.2 +/- 6 mm Hg, p = 0.9). Left ventricular outflow tract velocity decreased on tilting in control subjects (-8 +/- 6 cm/sec, p = 0.004) but increased in the syncopal and nonsyncopal patients (20 +/- 50 cm/sec, p = 0.05). Reflex hypotension with or without bradycardia, associated with syncope or presyncope, was induced in seven syncopal patients, two nonsyncopal patients, and two control subjects (p = 0.05). The early response to tilt in these subjects was characterized by maintenance of blood pressure but a greater increase in left ventricular fractional shortening than in the other subjects (10 +/- 8% versus 1 +/- 1%, p = 0.002). The onset of hypotension was associated with a trend toward further decreases in left ventricular diameters, outflow tract velocity, and transmitral flow velocities. In the remaining patients who had a negative test, transient hypotension (systolic pressure less than 100 mm Hg) occurred in seven syncopal patients and three nonsyncopal patients compared with none of the control subjects (p = 0.01). In total, hypotension was demonstrated in 82% of syncopal patients compared with 26% of nonsyncopal patients and 22% of control subjects (p = 0.001). CONCLUSIONS: Patients with hypertrophic cardiomyopathy and a history of syncope frequently display hypotension during head-up tilt. In some cases, sudden hypotension occurs and is usually associated with bradycardia and a reduced cavity size, findings compatible with activation of a ventricular baroreflex. In other cases, transient hypotension occurs and could be explained by an impairment of baroreceptor function. These mechanisms may contribute to the occurrence of syncope in daily life. PMID- 1591833 TI - Elimination of atrioventricular nodal reentrant tachycardia using discrete slow potentials to guide application of radiofrequency energy. AB - BACKGROUND: Ablation of the slow pathway has been performed to eliminate atrioventricular (AV) nodal reentrant tachycardia (AVNRT) either by a surgical approach or by using radiofrequency catheter technique guided by retrograde slow pathway activation mapping. From previous experience of midseptal and posteroseptal mapping, we were aware of the existence of peculiar slow potentials in most humans. Postulating their role in AVNRT, we studied these potentials and the effects of radiofrequency energy. METHODS AND RESULTS: Sixty-four patients (mean age, 48 +/- 19 years) with the usual form of AVNRT were studied. Slow, low amplitude potentials were recorded when using the anterograde AV conducting system. Slow potentials occupied all (giving a continuum of electrograms) or some of the time between the atrial and ventricular electrograms. Their most specific patterns were their progressive response to increasing atrial rates, which resulted in a dramatic decline in amplitude and slope, a corresponding increase in duration, and a separation from preceding atrial potentials until the disappearance of any consistent activity. Slow potentials were recorded along a vertical band at the mid or posterior part of the septum near the tricuspid annulus. Radiofrequency energy applied at the slow potential site resulted in interruption of induced tachycardia within a few seconds and rendered tachycardia noninducible in all patients. A median of two impulses was delivered to each patient. In 69% of patients, postablation atrial stimulation cannot achieve a long atrial-His interval, which previously was critical for tachycardia induction or maintenance. No patient had AVNRT over a follow-up period of 1-16 months, and all had preserved AV conduction. In all except two patients, the PR interval was unchanged. In 47 patients, long-term electrophysiological studies confirmed the efficacy of ablation and the nonreversibility of results by isoproterenol; however, echo beats remained inducible in 40% of patients. CONCLUSIONS: An area showing slow potentials is present at the perinodal region in humans. In patients with AVNRT, application of radiofrequency energy renders tachycardia noninducible through the preferential modification of the anterograde slow pathway. With present clinical methods, the exact origin and significance of these physiological potentials cannot be specified. PMID- 1591834 TI - Quantitative histological analysis of the human sinoatrial node during growth and aging. AB - BACKGROUND: Fibrosis or fatty infiltration of the human sinoatrial (SA) node is generally believed to represent replacement of the SA nodal cells by connective tissue. Quantitative analysis, however, has not been performed precisely to validate the interpretation of such histological changes. METHODS AND RESULTS: The actual volume of the SA node and its components were calculated according to the sum of the pixel number representing the colors of SA nodal cells and connective tissue in serial sections using a digital color image analyzer. Average volume occupied by the total SA nodal cells in adolescents and adults (n = 7) was 3.55 +/- 0.45 mm3, which was 2.4 times greater than that in infants (n = 3). The rate of increase was smaller than that of the total SA node (4.2 times, 16.68 +/- 2.56 mm3 in adolescents and adults). The considerable discrepancy in the growth ratio between the SA nodal cells and the total SA node resulted from an increase in the volume of connective tissue (7.4 times). In the elderly (n = 9), the volume of total SA node and SA nodal cells actually decreased (13.10 +/- 1.85 mm3 and 2.18 +/- 0.44 mm3), whereas that of fibrous connective tissue remained unchanged. Constant DNA ploidy patterns of SA nodal cells determined by cytofluorometry indicated that SA nodal cells never synthesize DNA during growth. CONCLUSIONS: Until adulthood, the actual volume of SA nodal cells does not decrease, although the increase in volume ratio of the interstitial tissue to the total SA node has merely given a false impression of involution of SA nodal cells. Atrophy of SA nodal cells, however, occurs during aging together with reduction of the SA node and/or infiltration of fatty tissue. PMID- 1591835 TI - In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty. AB - BACKGROUND: The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo. METHODS AND RESULTS: To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury. CONCLUSIONS: These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified. PMID- 1591836 TI - Association between rheology and components of lipoproteins in human blood. Results from the MONICA project. AB - BACKGROUND: Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies. METHODS AND RESULTS: We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin. CONCLUSIONS: We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study. PMID- 1591837 TI - Lipids and other risk factors selected by discriminant analysis in symptomatic patients with supra-aortic and peripheral atherosclerosis. AB - BACKGROUND: Different patterns of risk factors might be related to the involvement of specific vascular districts by atherosclerosis. In this sense, many investigations have addressed coronary artery disease, whereas extracoronary atherosclerosis has received less extensive attention. METHODS AND RESULTS: Vascular risk factors, with particular attention to lipid parameters (total cholesterol [TC]; triglycerides; high density lipoprotein cholesterol [HDL-C], HDL2 and HDL3 cholesterol [HDL2-C, HDL3-C]), were evaluated by means of univariate and multivariate (discriminant) analysis in a group of 169 patients (128 men and 41 women; mean ages, 58 +/- 7 and 62 +/- 7 years, respectively) with clinically and angiographically demonstrated atherosclerosis of the supra-aortic trunk and/or lower limbs. Patients with coronary artery disease were excluded from this study. The control group consisted of 140 age- and sex-matched individuals. By univariate analysis, smoking was more closely associated with peripheral atherosclerosis, whereas blood pressure was higher in patients with supra-aortic disease. Unrecognized diabetes mellitus was a frequent finding in patients with peripheral disease. The percentage of hyperlipidemias was fourfold higher in patients than in control subjects, with differences consisting of higher triglycerides and lower HDL-C, HDL2-C, and HDL3-C concentrations. By discriminant analysis, high correct classification (CC) rates were achieved in the various patient subgroups on the basis of variables selected from the statistical function. In male patients with peripheral disease, the variables HDL C, smoking, diastolic blood pressure, uric acid, and glucose, in that order, yielded a CC in 90.4% of the cases; in female patients, smoking, TC/HDL-C, and body mass index gave a CC rate of 95.9%. In men with cerebral disease, the selected variables TC/HDL-C, diastolic blood pressure, and TC yielded a CC of 90.7%; in women, uric acid, TC/HDL-C, and fibrinogen levels produced a CC rate of 89.2%. CONCLUSIONS: Risk profiles in atherosclerosis of the supra-aortic trunks and lower limbs seem to differ in relation to gender and circulatory district involved. The importance of lipid parameters, in particular HDL-C, HDL2-C, and TC/HDL-C, as extracoronary risk factors is further confirmed. PMID- 1591838 TI - Postischemic recovery of mitochondrial adenine nucleotides in the heart. AB - BACKGROUND: Adenine nucleotides (AdNs) are lost from the mitochondrial fraction of the heart cell during ischemia. It is unknown whether this pool of AdNs can be replenished after reperfusion. The purpose of this study was to evaluate the postischemic recovery of the mitochondrial AdN pool. METHODS AND RESULTS: The left anterior descending coronary artery (LAD) of the canine heart was occluded for 30 minutes followed by either no reflow, 30-minute reflow, 1-day reflow, or 7 day reflow. Systolic shortening in the LAD-supplied region was absent during occlusion but recovered to approximately 30% of preocclusion values during early reperfusion. Mitochondrial and tissue AdNs (ATP, ADP, and AMP) were determined in the LAD-supplied and left circumflex-supplied (control) regions of the heart. The AdN content (expressed as percent of control values) of mitochondria from the LAD region was 55 +/- 10% (p less than 0.002), 64 +/- 7% (p less than 0.001), 81 +/- 6% (p less than 0.03), and 94 +/- 8% for the no-reflow, 30-minute-reflow, 1-day reflow, and 7-day-reflow groups, respectively. The AdN content (expressed as percent of control values) of tissue samples from the LAD region was 52 +/- 9% (p less than 0.002), 48 +/- 12% (p less than 0.02), 68 +/- 5% (p less than 0.002), and 70 +/- 9% for the no-reflow, 30-minute-reflow, 1-day-reflow, and 7-day-reflow groups, respectively. There was a good correlation between mitochondrial and tissue AdN (r = 0.95). Using initial exchange rates, adenine nucleotide translocase activities of mitochondria from the LAD and control regions were not significantly different. State 3 respiration of LAD mitochondria was depressed (approximately 25%, p less than 0.05) only in the no-reflow group. Acceptor control ratios of the LAD mitochondria were not significantly different from control values in any group. CONCLUSIONS: After 30 minutes of regional ischemia, postischemic restoration of the mitochondrial AdN pool occurs between 1 and 7 days; this restoration is preceded by recovery of respiratory and adenine nucleotide translocase functions. Although the abnormally low levels of AdN persist in the mitochondrial compartment during the early reperfusion period, postischemic contractile dysfunction cannot be explained by depressed mitochondrial respiratory activity. PMID- 1591839 TI - Preconditioning does not attenuate myocardial stunning. AB - BACKGROUND: Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown. METHODS AND RESULTS: We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5 minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15 minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning. CONCLUSIONS: Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow. PMID- 1591841 TI - Doppler assessment of prosthetic valve orifice area. An in vitro study. AB - BACKGROUND: Although Doppler echocardiography has been shown to be accurate in assessing stenotic orifice areas in native valves, its accuracy in evaluating the prosthetic valve orifice area remains undetermined. METHODS AND RESULTS: Doppler estimated valve areas were studied for their agreement with catheter-derived Gorlin effective orifice areas and their flow dependence in five sizes (19/20-27 mm) of St. Jude, Medtronic-Hall, and Hancock aortic valves using a pulsatile flow model. Doppler areas were calculated three ways: using the standard continuity equation; using its simplified modification (peak flow/peak velocity); and using the Gorlin equation with Doppler pressure gradients. The results were compared with Gorlin effective orifice areas derived from direct flow and catheter pressure measurements. Excellent correlation between Gorlin effective orifice areas and the three Doppler approaches was found in all three valve types (r = 0.93-0.99, SEE = 0.07-0.11 cm2). In Medtronic-Hall and Hancock valves, there was only slight underestimation by Doppler (mean difference, 0.003-0.25 cm2). In St. Jude valves, however, all three Doppler methods significantly underestimated effective orifice areas derived from direct flow and pressure measurements (mean difference, 0.40-0.57 cm2) with differences as great as 1.6 cm2. In general, the modified continuity equation calculated the largest Doppler areas. When orifice areas were calculated from the valve geometry using the area determined from the inner valve diameter reduced by the projected area of the opened leaflets, Gorlin effective orifice areas were much closer to the geometric orifice areas than Doppler areas (mean difference, 0.40 +/- 0.31 versus 1.04 +/- 0.20 cm2). In St. Jude and Medtronic-Hall valves, areas calculated by either technique did not show a consistent or clinically significant flow dependence. In Hancock valves, however, areas calculated by both the continuity equation and the Gorlin equation decreased significantly (p less than 0.001) with low flow rates. CONCLUSIONS: Doppler echocardiography using either the continuity equation or Gorlin formula allows in vitro calculation of Medtronic-Hall and Hancock effective valve orifice areas but underestimates valve areas in St. Jude valves. This phenomenon is due to localized high velocities in St. Jude valves, which do not reflect the mean velocity distribution across the orifice. Valve areas are flow independent in St. Jude and Medtronic-Hall prostheses but decrease significantly with low flow in Hancock valves, suggesting that bioprosthetic leaflets may not open fully at low flow rates. PMID- 1591840 TI - Effect of pulse separation between two sequential biphasic shocks given over different lead configurations on ventricular defibrillation efficacy. AB - BACKGROUND: Two sequential biphasic shocks delivered over separate lead configurations markedly improve defibrillation efficacy compared with a single shock alone. We investigated the effect of varying the intershock interval between sequential biphasic shocks on defibrillation. METHODS AND RESULTS: Defibrillation thresholds (DFTs) were obtained in six dogs for shock separations ranging from 0.2 to 125 msec. The first shock was given from a catheter electrode in the right ventricular apex to a patch on the left lateral thorax; the second was from a small patch on the left ventricular apex to a catheter electrode in the right ventricular outflow tract. When the interval between shocks was less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec, the mean DFTs were less than that previously found for the first shock by itself (4.2 versus 7.4 J, p = 0.002). At a separation of 50 msec, however, there was a marked rise in the DFT to 27 J. The mean DFT for the second shock at a delay of 50 msec was not different from the mean DFT previously found for the second shock by itself (7.2 versus 7.0 J). These results were confirmed in another six dogs using defibrillation probability-of-success curves. In 12 other dogs, probability-of-success curves were generated for delays between shocks as a percentage of the activation interval during ventricular fibrillation. Minimum defibrillation energy requirements were at two separations, 0.2 msec and 90% of the activation interval. CONCLUSIONS: The optimal intershock interval between two sequential biphasic shocks is either less than or equal to 10 msec or greater than or equal to 75 and less than or equal to 125 msec. The marked rise in the DFT at a shock separation of 50 msec, requiring more energy than that for the first shock alone, suggests that the second shock at this time delay is likely to reinduce fibrillation after it is halted by the first shock until the second shock is strong enough to defibrillate independently of the first shock. PMID- 1591842 TI - Nitric oxide functions as an inhibitor of platelet adhesion under flow conditions. AB - BACKGROUND: Nitric oxide (NO) has been identified as endothelium-derived relaxing factor (EDRF), which, in addition to its relaxant effects on vascular smooth muscle cells, is also a potent inhibitor of platelet aggregation. An inhibitory role on platelet adhesion has been suggested from experiments with washed platelets under static conditions. We have determined whether endothelium-derived and exogenous NO also regulates platelet adhesion in whole blood under flow conditions. METHODS AND RESULTS: The effect of endothelium-derived NO was studied by the addition of specific inhibitors of NO production, L-N-monomethyl arginine (L-NMMA) and N-iminoethyl-L-ornithine (L-NIO), to a perfusion system in which both endothelial cells and their matrices were present. A concentration-dependent increase in platelet adhesion to the matrix was found with a maximum inhibition at a concentration of 2 mM L-NMMA and 0.1 mM L-NIO. The effect was dependent on the presence of endothelial cells, because no increase in platelet adhesion was observed in their absence. The effect of exogenous NO was tested in a specially devised perfusion system in which the NO was introduced at the site of adhesion by means of a porous membrane on which an extracellular matrix of endothelial cells was present. Inhibition of platelet adhesion by NO was found at all shear rates tested and after all perfusion periods. CONCLUSIONS: These results demonstrate that NO is a potent inhibitor of platelet adhesion under flow conditions and thereby contributes to the regulatory role of vascular endothelial cells on platelet-vessel wall interaction. PMID- 1591843 TI - Intraluminal ultrasound imaging through a balloon dilation catheter in an animal model of coarctation of the aorta. AB - BACKGROUND: Controversy still exists over the optimal balloon size, extent of vascular disruption, and long-term results of balloon dilation therapy for coarctation of the aorta. Intravascular ultrasound imaging has been used in patients with coronary artery disease to provide further insight into the anatomy of atherosclerotic lesions and the results of angioplasty and atherectomy. Initial observations of the results of balloon dilation of coarctations with intravascular ultrasound imaging have shown prominent dissections of the inner vascular layers that are often not detected by angiography. The purpose of this study was to test a new transballoon catheter ultrasonic imaging system capable of on-line direct visualization of lumen diameter and vessel wall structure for imaging before, during, and after dilation in an acute animal model of aortic coarctation. METHODS AND RESULTS: Abdominal aortic coarctations were created surgically in three 14-19-kg mongrel dogs by using Teflon gauze ties. The 6.8F ultrasound balloon catheter was placed percutaneously in the right femoral artery through a 9F sheath. Ultrasound imaging allowed measurement of the coarctation diameter, characterization of the vessel wall structure, localization of the stenosis, and placement of the midportion of the balloon at the narrowest area. Imaging through the balloon was performed through several dilations (five to eight per animal), and after balloon deflation, it provided information on postdilation diameter, intimal tears, long-segment dissections, and intramural thrombi, findings that were confirmed at postmortem examination. CONCLUSIONS: The results of this study demonstrate that imaging with a new intraballoon ultrasound device is feasible during inflation to therapeutic dilation pressures; it allows visualization of the changes in diameter and vascular wall structure after serial dilations without having to recross the obstructed area. Adaptation to larger balloon sizes and lower frequencies should make this system applicable to interventional catheterizations in patients with congenital cardiac and vascular lesions. PMID- 1591845 TI - Intravascular ultrasound: a histological study of vessels during life. The new 'gold standard' for vascular imaging. PMID- 1591844 TI - Effect of intracoronary nitroglycerin administration on phasic pattern and transmural distribution of flow during coronary artery stenosis. AB - BACKGROUND: Nitroglycerin is effective in relieving myocardial ischemia; however, intracoronary nitroglycerin often fails to relieve angina and has been reported to have deleterious effects on subendocardial blood flow. To understand the mechanisms involved, we evaluated the direct effect of nitroglycerin on coronary circulation of the ischemic hearts. METHODS AND RESULTS: We measured the phasic pattern of intramyocardial coronary arterial flow with an 80-channel, 20-MHz pulsed Doppler ultrasound flowmeter under moderate to severe coronary artery stenosis (distal perfusion pressure approximately 45 mm Hg group 1, n = 6) and transmyocardial blood flow distribution using radioactive microspheres while maintaining coronary pressure at a low constant level (40 mm Hg, group 2, n = 6). In anesthetized open-chest dogs, the left main coronary artery was perfused directly from the right carotid or femoral artery. In this bypass circuit, pressure was controlled with an occluder or a reservoir was connected to the circuit. In group 1, the systolic and diastolic pressures distal to the stenosis decreased significantly after intracoronary administration of nitroglycerin at maximal coronary flow from 66.5 +/- 18.5 to 56.5 +/- 13.8 mm Hg (p less than 0.01) and from 36.6 +/- 14.4 to 27.5 +/- 8.9 mm Hg (p less than 0.01), respectively. The phasic pattern of the septal artery flow was predominantly diastolic and was characterized by systolic reverse flow even in the absence of stenosis. Coronary stenosis increased systolic reverse flow. Nitroglycerin increased diastolic forward flow (p less than 0.05) but augmented systolic reverse flow markedly (p less than 0.001). In group 2, nitroglycerin increased subepicardial flow (p less than 0.05) but failed to increase subendocardial flow. With the administration of nitroglycerin, the subendocardial-to-subepicardial flow ratio decreased significantly from 0.73 +/- 0.19 to 0.32 +/- 0.14 (p less than 0.01). CONCLUSIONS: The increased systolic reverse flow after intracoronary administration of nitroglycerin may be closely related to failure of subendocardial blood flow to increase with increase subepicardial flow. PMID- 1591846 TI - Timing of coronary recanalization. Paradigms, paradoxes, and pertinence. PMID- 1591847 TI - Implantable defibrillators for prevention of sudden death. Technology at a medical and economic crossroad. AB - Implantable cardioverter-defibrillator therapy is now widely used for the treatment of symptomatic patients with documented or suspected life-threatening VTs. Although sudden death recurrence in ICD recipients is virtually eliminated, the extent of benefit both with respect to cardiac mortality and total survival in this patient population remains to be accurately quantitated, particularly vis a-vis alternative antiarrhythmic therapies. Advanced device and lead systems can be expected to further improve both patient survival and quality of life after implant. The economic impact of unrestrained proliferation in ICD therapy can be enormous; however, available cost-benefit analyses support judicious use of this therapy with comparable economic impact to other accepted cardiovascular therapies. Such prospective risk stratification becomes economically essential when considering expanding its application to asymptomatic or minimally symptomatic populations at potential risk for future cardiac arrest. PMID- 1591848 TI - Spectral electrocardiographic mapping for ventricular tachycardia. Another promising aspect of high-resolution electrocardiography. PMID- 1591849 TI - Exercise training in heart failure patients. Does reversing the peripheral abnormalities protect the heart? PMID- 1591850 TI - Blood viscosity, lipoproteins, and cardiovascular risk. PMID- 1591851 TI - Antiphospholipid antibodies and the heart. PMID- 1591852 TI - Delay in response to acute myocardial infarction. PMID- 1591853 TI - Polymorphous ventricular tachycardia associated with acute myocardial infarction. PMID- 1591854 TI - Nifedipine reduces the incidence of myocardial infarction and transient ischemia in patients undergoing coronary bypass grafting. PMID- 1591855 TI - Antioxidants in the prevention of human atherosclerosis. Summary of the proceedings of a National Heart, Lung, and Blood Institute Workshop: September 5 6, 1991, Bethesda, Maryland. PMID- 1591856 TI - Report of the American Heart Association Task Force on the Future of Cardiopulmonary Resuscitation. PMID- 1591857 TI - Comparison of soluble aminopeptidases in human cerebral cortex, skeletal muscle and kidney tissues. AB - In an attempt to elucidate the cellular function of the soluble aminopeptidases (with which the majority of tissue aminopeptidase activity is usually associated) we have determined the distribution and characteristics of these enzymes in three functionally dissimilar human tissues (cerebral cortex, skeletal muscle and kidney cortex), using a systematic experimental approach. Following fractionation of brain, muscle or kidney soluble extracts via anion exchange chromatography, four aminopeptidase enzymes types (alanyl-, arginyl-, leucyl- and pyroglutamyl-) were identified; the absolute and relative activities for corresponding enzymes were similar in each tissue. Following further purification of each enzyme type from each tissue (via liquid chromatography/preparative electrophoresis), corresponding enzyme types were found to have similar characteristics (pH optimum of activity, action of enzyme effectors, substrate specificity and molecular mass). Since the same enzymes, with correspondingly similar distribution and characteristics are present in such functionally dissimilar tissues, it is suggested that the principal role for the soluble aminopeptidases (in contrast to the membrane-associated enzymes, which may function in the catabolism of neuropeptides) is in the final stages of the general intracellular protein catabolism cascade, via hydrolysis of oligopeptide intermediates to free amino acids. PMID- 1591858 TI - Enzyme-linked immunosorbent assay for serum pseudocholinesterase. AB - We developed a reliable enzyme-linked immunosorbent assay using purified pseudocholinesterase (ChE) as a standard and its monoclonal antibody. The precision, reproducibility, and sensitivity of this assay were quite satisfactory. Serum ChE concentration in 506 normal individuals ranging from 20 to 60 years of age was 3.78 +/- 0.32 mg/l (mean +/- 1 S.D.), though age- and sex related differences were present. Measurements of ChE concentration and ChE enzymatic activity by two different assay kits in 63 serum samples taken in the Clinical Laboratory of the Jichi Medical School correlated closely. Quantitative determination of serum ChE concentration can be clinically useful: it is much easier and requires far less restricting conditions than does determination of ChE enzymatic activity. Also, it can be performed quite easily under far less demanding conditions. Further, the method is easy to standardize, and this standardization may be applied when the assay is used to evaluate ChE enzymatic activity. PMID- 1591859 TI - The effect of blood sample aging and food consumption on plasma total homocysteine levels. AB - The stability of homocysteine in whole blood and plasma was investigated. Total homocysteine concentrations in whole blood increased rapidly to values in excess of 180% of the basal concentration if whole blood was left at ambient temperature. Sodium fluoride partially inhibited homocysteine accumulation, while refrigeration inhibited homocysteine accumulation for at least 4 h. Since intracellular concentrations of homocysteine were low, the results indicate continued metabolism of L-methionine to homocysteine after the blood sample had been obtained. In contrast to whole blood, homocysteine was stable in plasma, even at room temperature. Food consumption (normal breakfast) resulted in significantly lower plasma homocysteine concentrations, which returned to pre prandial concentrations 8 h later. The results indicate that both blood sampling and food intake should be rigorously standardized in epidemiological studies to elucidate the possible role of elevated circulating homocysteine concentrations in premature vascular disease. PMID- 1591860 TI - A case of Hashimoto's thyroiditis with antibodies to thyroid hormone analogues. PMID- 1591861 TI - Selenium, glutathione peroxidase (GSH-Px) and lipid peroxidation products before and after selenium supplementation. AB - Treated phenylketonuric (PKU) children are at risk of selenium deficiency. We have studied 15 treated PKU children and 30 control children. We observed significantly lower (P less than 0.0005) plasma and erythrocyte selenium, as well as significantly lower (P less than 0.0005) plasma and erythrocyte glutathione peroxidase activities (GSH-Px) in PKU children than in controls. The lipid peroxidation products, evaluated as plasma malondialdehyde (MDA), was higher (P less than 0.0005) in PKU children than in controls. Specific oral sodium selenite supplementation (Selenium: 0.13 mumol/kg/day) resulted in a rapid increase of plasma selenium and GSH-Px activity, and after 10 days and 1 month respectively significant difference is no longer observed between PKU children and controls values. Statistically significant differences in erythrocyte selenium, erythrocyte GSH-Px activity and plasma MDA between PKU and control children disappear after respectively 2 months, 4 months and 6 months of selenium supplementation. PMID- 1591862 TI - Critical evaluation of the serum kappa/lambda light-chain ratio in the detection of M proteins. PMID- 1591863 TI - Two cases of acatalasemia in Hungary. PMID- 1591864 TI - A specific method for determination of peroxisomal beta-oxidation activity in cultured human skin fibroblasts using a specific substrate, C9: a possible application for screening of peroxisomal disorders. AB - We developed a specific method for direct determination of peroxisomal beta oxidation activity in cultured human skin fibroblasts. When control fibroblasts were incubated with N-(alpha-methylbenzyl)azelaamic acid (C9), a specific peroxisomal substrate, C5 and C7, the chain-shortened products, were detected with cell concentration and incubation time dependencies and no other products including C3 were detected. In glutaric aciduria type I and type II fibroblasts, the formation rates of C2 units liberated from C9 were almost similar to that in control cells. In contrast to these cell types, the fibroblasts from patient of Zellweger syndrome, in which peroxisomal beta-oxidation was impaired, showed no conversion of C9 to C5 and C7. The lack of the C2 units liberation in Zellweger fibroblasts was not due to an impairment of mitochondrial beta-oxidation and/or activation of C9 to C9-CoA derivative for subsequent beta-oxidation reaction, but rather, appeared to be due to the specific defect of peroxisomal beta-oxidation system. These results indicate that C9 is a useful substrate for the estimation of peroxisomal beta-oxidation activity in cultured human skin fibroblasts. PMID- 1591865 TI - Serum analysis for potassium ions using a fibre optic sensor. AB - A fibre optic potassium ion sensor has been developed based on reflectance measurements of the pH-dependent chromogenic crown ether 'Takagi reagent' immobilized on the non-ionic polymeric resin Amberlite XAD2. The sensor response is in the 1.5-100 mM range with a detection limit of 0.25 mM K+. The selectivity factor over sodium is 20. The proposed sensor works with a reproducibility of +/- 0.8% at the 5 mM K+ level. Advantageous design features include ease of construction, simplicity of use, reversibility, short response time (approximately 1 min) and an optimum working pH range (7.0-8.0) for biological fluids. This optical sensor was applied successfully to the direct determination of potassium in human serum. Aqueous potassium standards containing 0.13 M NaCl and a buffer of pH 8 were used for calibration. PMID- 1591866 TI - Aluminum-binding serum proteins: desferrioxamine alters serum aluminum speciation. AB - The aluminum content of four size classes of protein (high and low molecular weight, transferrin/albumin and a fraction provisionally termed albindin) in sera from healthy volunteers (group I) and from aluminum workers with normal (group II) and high (group III) total serum aluminum was compared using size exclusion chromatography and electrothermal atomic absorption spectroscopy. In the absence of any drug treatment the transferrin/albumin fraction was the major carrier, containing 29% to 33% of the aluminum recovered, in all three subject groups. Desferrioxamine treatment of groups II and III significantly decreased the proportion of aluminum bound by albumin/transferrin (P less than 0.05 in group III) and increased that bound by albindin (P less than 0.05 in groups II and III). The albindin fraction contained over 40% of the aluminum recovered from sera of group III subjects during desferrioxamine treatment. We conclude that the albindin fraction contains a protein or proteins that can form stable complexes with aluminum which may be important in preventing aluminum toxicity. PMID- 1591867 TI - Insulin binding to erythrocytes of nonpregnant women: a reevaluation, underlining the importance of body weights even in nonobese subjects. AB - Insulin binding to erythrocytes was measured in 18 healthy, non-obese women in the follicular phase and in 6 women in the mid-luteal phase of the same menstrual cycle. The presence of 55 nM and 220 nM monoclonal anti-IGF I receptor antibody (alpha-IR3) reduced only the number of low affinity binding sites for insulin by 20% and 33%, respectively. Women with relative body weights 110-119% had a lower number of high affinity receptors and an increased high affinity compared to women with relative body weights 91-109%. In women with relative body weights greater than or equal to 100%, maximum specific binding and high affinity constants increased and the receptor numbers decreased from the follicular to the luteal phase, whereas in women with relative body weights less than 100% the parameter changes were reverted. The data indicate: (1) erythrocytes contain two different classes of binding sites for insulin, (2) IGF I receptors might contribute to low-affinity binding of insulin to erythrocytes and (3) the relative body weight must be considered even for 'non-obese' control groups used in insulin binding studies of various clinical conditions. PMID- 1591869 TI - Influence of triglycerides and urate on methods for determination of fructosamine. AB - The original fructosamine assay, based on reduction of NBT, has been modified and marketed as a kit. The development includes addition of detergents, uricase, change of the buffer and NBT concentrations, and use of a new calibrator. We report the effects of these changes on the measured values of fructosamine in lipemic and uricemic sera. A secondary calibrator produced from pooled serum and stabilized by removal of glucose was used to calibrate the original fructosamine assay and enhance transferability of results. There was no correlation between the difference between the results obtained by the two procedures and the concentration of urate or triglycerides. The development of colour was faster with the original method. It is suggested that measurements of fructosamine by either method are practically equivalent. However, the use of polylysine as a calibrator is advantageous. It is suggested that the generic term S-Glycated proteins is used for the measurand rather than S-Fructosamine which in effect has become a commercial term. PMID- 1591868 TI - Distribution of SP1, immunoreactivity among different plasma proteins: real molecular heterogeneity or adsorption of SP1-beta to other plasma proteins? AB - Three SP1-containing factors from pooled term pregnancy sera were subjected to crossed immunoelectrophoresis. New patterns as far as electrophoretic mobilities and shapes of the immunoprecipitates were revealed. The appearance of an additional anodic radioimmunoassayable activity in agarose electrophoresis of mixed SP1-alpha and SP1-beta suggested a binding capacity of SP1-alpha for SP1 beta determinants. In the serum of a single patient at the third trimester of pregnancy we also found two SP1 variants, possessing little radioimmunological reactivity and with crossed immunoelectrophoretic characteristics quite different from those of the 'usual' alpha and beta SP1 forms. These results suggest that, in this particular case, the overall SP1 production cannot be evaluated by competitive binding assay and, that in general, SP1 is a complex antigen the heterogeneity of which can be determined following adsorption of some beta epitopes to another serum protein. PMID- 1591870 TI - Giardia lamblia as an intestinal pathogen. AB - Giardia lamblia are protozoan parasites which cause human intestinal disease. The life cycle has a multiplying intraduodenal trophozoite and an excreted cyst. Infection occurs after cyst ingestion from faecally contaminated water or by direct faecal-oral transmission in situations of poor sanitary standards, but the zoonotic nature of giardiasis is debated. The pathophysiology may arise from enzyme or active transport deficiencies, synergy with intestinal bacteria or an immunopathological process. Diagnosis is made by microscopic identification of cysts or trophozoites in small bowel samples or faeces. Symptoms are acute with diarrhoea (without blood), abdominal cramps, bloating and flatulence. The treatment of choice is either metronidazole or tinidazole. No vaccine or drug prophylaxis exists, and measures to avoid cyst ingestion should be undertaken. PMID- 1591871 TI - Role of the gastrointestinal tract in the regulation of hydration in man. AB - Research into the role of the gastrointestinal tract in the regulation of hydration has primarily concentrated on its function in the prevention of dehydration. The role of the gut in thirst, in the absorption of fluids and the consequences of diarrhoea are of importance in this respect. The function of the gut in the prevention of overhydration is less well understood. Intake of fluid increases excretion of water by the kidney. Inhibition of arginine vasopressin secretion, activation of renal nerves or hormonal release are possible effector mechanisms in this response. PMID- 1591872 TI - Cigarette smoking and gastroesophageal reflux disease. AB - Proposed pathophysiologic mechanisms relating gastroesophageal reflux disease to cigarette smoking are reviewed. Acute experiments have shown that smokers have chronically diminished lower esophageal sphincter (LES) pressure and that periods of smoking are associated with an increased rate of reflux events. Reflux occurred primarily by the 'abdominal strain mechanism' rather than by transient LES relaxation. Smoking also caused chronically diminished salivary function that results in prolonged acid clearance time. Thus, smoking potentially increases esophageal acid exposure, both by increases in the number of reflux events, and a prolongation of the esophageal acid clearance time. PMID- 1591873 TI - Pathogenic factors in inflammatory bowel disease. 2. Crohn's disease. AB - Clues from patient and experimental animal studies suggest that events occurring early in the pathogenesis of Crohn's disease are related to an inability of the immune system to eradicate one or a number of luminal antigens resulting in persistent T cell and macrophage activation. Whether the primary abnormality rests with the nature of the luminal antigen, disturbances of antigen uptake by the mucosa, antigen handling by macrophages, or macrophage-T cell interactions remains unresolved. Given the heterogeneity of clinical presentations and experimental data, Crohn's disease may be a group of disorders associated with a number of primary defects. PMID- 1591874 TI - Cytokine abnormalities in human lupus. PMID- 1591875 TI - Pathogenetic significance of anti-lymphocyte autoantibodies in systemic lupus erythematosus. PMID- 1591876 TI - The importance of estrogens in systemic lupus erythematosus. PMID- 1591877 TI - Concepts of pathogenesis of systemic lupus erythematosus. AB - It is likely that different disease-inducing factors interfere with normal immune regulatory processes in different patients (1, 3). Some people may have such a strong genetic predisposition to disease that environmental insults may not be very important. Other individuals, with a much weaker genetic predisposition, may require strong environmental stimulation for disease induction (2). Defects in self-tolerance mechanisms could provide the genetic basis of disease or the target for environmental triggers. However, induction and perpetuation of pathogenic autoantibody production may frequently be a "multi-hit" process. The greater the number and/or degree of abnormalities (genetic and environmental), the greater the probability of disease. PMID- 1591878 TI - Serum tumor necrosis factor and interleukin 1 in leprosy and during lepra reactions. AB - Tumor necrosis factor--alpha (TNF), one of the mediators of septic shock, has a role in the immunopathological complications of several infections. However, its role in leprosy is yet unclear. In this study, serum TNF and IL-1 levels in 64 patients spread over the spectrum of leprosy [lepromatous leprosy (LL), 30; borderline lepromatous, 12; borderline borderline, 8; and borderline tuberculoid tuberculoid leprosy, 14] were measured at the time of admission. Elevated levels of TNF ranging from 15 to 4500 pg/ml were detected in lepromatous leprosy cases (399 +/- 189) and low levels ranging from 15 to 160 pg/ml were detected in the tuberculoid form of leprosy. Patients undergoing type 1 and type 2 lepra reactions also exhibited high TNF levels of 15-2100 pg/ml. Of the 14 clinically healthy individuals studied, 3 showed TNF levels of 15, 50, and 58 pg/ml. Interleukin 1-beta (IL-1) levels were found to be significantly higher in LL cases (70-5000 pg/ml) (328 +/- 184) in comparison to other groups or normal controls (9 +/- 3). The coefficient of correlation between TNF and IL-1 levels was statistically significant in LL and reaction cases (r = 0.96, P less than 0.001). These patients were followed up as outpatients for a period of 1 year. It was observed that 4 out of 8 patients with TNF levels greater than 100 pg/ml went into lepra reactions between 2 and 6 months after entry into the study, whereas only 5 out of 56 with less than 100 pg/ml went into mild lepra reactions (chi 2 = 9.7, P less than 0.01). Determination of TNF and IL-1 levels thus seems to have a prognostic significance in terms of lepra reaction in patients. PMID- 1591879 TI - Pathogenesis of human systemic lupus erythematosus. Introduction. PMID- 1591880 TI - A correlation between IgG class antibody production and glomerulonephritis in the murine chronic graft-versus-host reaction. AB - A graft-versus-host reaction (GVHR) was induced in (B10 x DBA/2)F1 (BDF1) and (BALB/c x A)F1 (CAF1) murine recipients by injection of their parental or B10.D2 derived spleen cells. The incidences of glomerulonephritis and autoantibody production were then correlated. All of the BDF1 mice that received DBA/2 spleen cells (termed DBA/2----BDF1) and 33% of the CAF1 mice that received BALB/c spleen cells (BALB/c----CAF1) developed glomerulonephritis. However, in other combinations (B10.D2----BDF1, A/J----CAF1) no significant glomerular lesions were observed. An analysis of antibodies by ELISA revealed that the groups with renal disease showed a significant polyclonal elevation of IgG class antibodies, including autoantibodies (anti-DNA, anti-MRBC, and NTA) and a conventional antibody (anti-TNP-KLH). No significant IgG class antibody production was observed in the groups that did not develop glomerulonephritis. Thus, it was suggested that an IgM to IgG class switch is important in the development of glomerulonephritis in GVHR. Other factors also appear to be involved. Only 33% of BALB/c----CAF1 developed glomerulonephritis, even though a level of IgG class antibody production was comparable to that observed in DBA/2----BDF1 in which 100% showed severe glomerulonephritis. PMID- 1591881 TI - The effect of lipid peroxides and superoxide dismutase on systemic lupus erythematosus: a preliminary study. AB - Serum lipid peroxide (LPO) levels, superoxide dismutase (SOD) activity in peripheral blood erythrocytes, serum ANA, anti-dsDNA, and C3 were measured in 83 patients with systemic lupus erythematosus (SLE) and in 29 healthy controls. Compared to the controls, LPO levels were significantly increased in active SLE patients while SOD activity was markedly decreased. From the active phase to the inactive phase, a gradual decline in LPO levels and an increase in SOD activity were observed. There was a close correlation between LPO levels and disease activity or the parameters including ANA titers, anti-DNA titers, and C3 levels; a significant negative correlation was found between SOD activity and LPO levels or these parameters. Further, a marked difference in SOD activity was found in untreated active cases with and without nephritis. As the SLE patients improved, LPO levels gradually declined and SOD activity increased. The present study indicates that free radicals and resultantly formed lipid peroxide levels are higher in patients with SLE than those in normal persons, probably contributing to the production of autoantibodies, nephritis, and vasculitis of other organs, and that excessively generated free radicals may play an important role in the pathogenesis of SLE, which is possibly due to diminished SOD activity. PMID- 1591882 TI - Platelet interactions with C1q in whole blood and in the presence of immune complexes or aggregated IgG. AB - Previous studies identified specific receptors for C1q on human blood platelets in purified systems using monomeric C1q. To assess the physiologic potential of platelet C1q receptors, C1q binding was evaluated in whole blood and in the presence of immune complexes or aggregated IgG. Blood was obtained from healthy volunteers and collected directly into EDTA (1 vol 100mM EDTA:9 vol whole blood) and purified, 125I-labeled C1q or 125I-C1q associated with albumin-anti-albumin immune complexes. Samples were incubated at 22 or 37 degrees C for 60 min, and total cell bound C1q and platelet associated C1q were quantified. Platelet-bound, monomeric C1q or immune complex-associated C1q represented 40-50% of total peripheral blood cell-associated C1q. C1q binding was unaffected by the incubation temperature, but the preincubation of 125I-C1q with immune complexes enhanced binding two- to threefold. This binding was partially inhibited by preincubating platelets with either the collagen-like amino-terminal fragments of C1q (c-C1q) or a monoclonal antibody Fab fragment recognizing platelet Fc receptors. A more complete inhibition was achieved if platelets were preincubated with both agents. Similar observations were made using washed platelets and 125I C1q associated with aggregated IgG. The role of C1q and platelet C1q receptors in enhancing aggregated-IgG binding to platelets was further supported by experiments demonstrating increased 125I-aggregated IgG binding to platelets not only after preincubation of 125I-aggregated IgG with C1q but also following platelet preincubation with C1q. These data suggest that C1q receptors may participate in the localization and presentation of C1q-associated immune complexes on the platelet surface and demonstrate that platelets contribute significantly to the C1q binding activity of peripheral blood. PMID- 1591883 TI - Smooth muscle and epithelial cells express specific binding sites for the C1q component of complement. AB - In injury and inflammation, interactions of complement C1q with C1q receptors may provide attachment sites for cell localization and tissue regeneration. Cultured smooth muscle cells (58%), epithelial cells (26%), and endothelial cells (25%) attach to C1q-coated surfaces, while only 6% of cultured B cells (Raji) attach. Endothelial and Raji cells express C1q receptors, but C1q receptors (C1qR) on smooth muscle cells and epithelial cells have not previously been demonstrated. Evidence is provided that smooth muscle cells express an average of 1.5 x 10(6) C1qR/cell (K alpha = 10(8) M-1) and that epithelial cells express an average of 0.7 x 10(6) C1qR/cell (K alpha = 1.4 x 10(8) M-1). Binding properties of C1qR, and immunoreactivity to anti-C1qR antibodies, are characterized. The antibodies specifically recognize a 67-kDa component of smooth muscle cell lysates and inhibit cell attachment to C1q substrates. We conclude that distribution of C1qR may be ubiquitous; binding properties, size, and antigenicity of various C1qR may be related, but adhesive function may be tissue specific. PMID- 1591884 TI - Presence of autoantibodies to peptidyl-prolyl cis-trans isomerase (cyclosporin A binding protein) in systemic lupus erythematosus. AB - Several autoantibodies against cytoplasmic or nuclear components of cells have been reported in autoimmune diseases. We report here a previously unrecognized autoantibody to peptidyl-prolyl cis-trans isomerase (PPIase) in patients with systemic lupus erythematosus (SLE). PPIase, which catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides, has recently been found to be identical to cyclophilin, a specific binding protein of a potent immunosuppressant, cyclosporin A. IgG and IgM anti-PPIase antibodies were detected in 40 and 20% of unselected patients with SLE, respectively, by ELISA. The reactivity of these sera was confirmed by immunoblotting experiments. Sera from rheumatoid arthritis patients showed no reactivity and 1 of 8 sera from systemic sclerosis patients and 1 of 25 sera from normal controls showed only weak reactivity. Unexpectedly, the anti-PPIase antibody was unable to inhibit PPIase activity, indicating that the autoantibody recognizes an epitope of PPIase which is different from the active site of PPIase. The levels of the anti-PPIase antibody in SLE patients correlated with remissions and flares of the disease. The anti-PPIase antibody was higher in patients with active SLE than those with inactive disease. The prevalence of the active stage of the disease was significantly higher in IgG anti-PPIase antibody-positive SLE patients as compared to antibody-negative SLE patients. These data define the presence of a new autoantibody against PPIase and its association with the activity and certain clinical manifestations in SLE. PMID- 1591885 TI - Effects of in vivo administration of interferon (IFN)-gamma, anti-IFN-gamma, or anti-interleukin-4 monoclonal antibodies in chronic autoimmune graft-versus-host disease. AB - These studies examined the role of cytokines in chronic autoimmune graft-versus host disease (GVHD) in B6D2F1 mice injected with lymphoid cells from DBA/2 mice. Anti-interleukin (IL)-4 and anti-interferon (IFN)-gamma mAb, or IFN-gamma, were used in vivo to modulate B cell hyperactivity and disease. Kinetic experiments showed that, 2-3 weeks after induction, GVH mice had 100x elevated serum IgE, while IgG1 and IgG2a were 10x above normal. Early treatment with anti-IL-4 mAb or IFN-gamma decreased serum IgE and IgG1 and had no effect on IgG2a. Anti-IFN-gamma mAb treatment increased serum IgE and IgG1 while reducing IgG2a. This increase in serum immunoglobulins could be correlated with an increased spontaneous secretion of IL-4, IL-5, and IL-6 in spleen cell cultures from anti-IFN-gamma mAb-treated GVH mice. While neither anti-IFN-gamma nor IFN-gamma treatments altered the disease course, anti-IL-4 treatment delayed proteinuria and death in GVH mice. These observations suggest an important role for IL-4 in immune complex-mediated glomerulonephritis in chronic GVHD. PMID- 1591886 TI - Lymphocyte abnormalities in human lupus. PMID- 1591887 TI - IgG subclass restriction of autoantibody to solid-phase C1q in membranoproliferative and lupus glomerulonephritis. AB - The IgG subclass distribution for autoantibodies to solid-phase C1q (anti-spC1q) in sera from 14 patients with membranoproliferative glomerulonephritis (MPGN) and 10 patients with systemic lupus erythematosus (SLE) nephritis was determined by an enzyme-linked immunosorbant assay employing C1q as the immunosorbant in the presence of 2 M NaCl to prevent Fc binding and monoclonal anti-human IgG subclass reagents. The autoantibody to spC1q in MPGN, especially in types I (7 patients) and II (3 patients), was almost entirely restricted to IgG3. In contrast, in SLE anti-spC1q was completely restricted to IgG2 in 3 patients while predominantly IgG2 in the other 7 patients. The different subclass restriction of anti-spC1q in these two disorders suggests that antibody formation is either in response to different epitopes on the collagen-like region of C1q or that patients with SLE and MPGN mount different immunologic responses to the same antigenic stimulus. PMID- 1591888 TI - Antigenic specificities of glomerular-bound autoantibodies in membranous glomerulopathy induced by mercuric chloride. AB - The present study describes the development of membranous glomerulopathy (MGP) with high proteinuria in DZB rats exposed to mercuric chloride (HgCl2). IgG1 and IgG2a antibodies, eluted from glomeruli with subepithelial immune deposits, bind to the interface of the GBM and epithelial cells. High reactivity to GBM was demonstrated by ELISA and Western blotting, which could be absorbed for 30% by laminin or laminin-associated extracellular matrix components. No reactivity was found with type IV collagen, fibronectin, heparan sulfate proteoglycans, or tubular brush border antigens. Absorption to GBM removed the reactivity to renal antigens. Passively transferred eluted antibodies bind in a predominantly linear pattern along the GBM, causing focal ultrastructural transformations of the podocytes. These results suggest that this type of HgCl2-induced MGP, associated with epithelial cell injury and proteinuria, is caused by autoantibodies to basement membrane components which are located at the epithelial cell-basement membrane interface and may be involved in cell-matrix binding. PMID- 1591889 TI - Long-term care equals worthwhile care. PMID- 1591890 TI - 1991 CSCI Distinguished Scientist Award. PMID- 1591891 TI - CSCI Distinguished Service Award. PMID- 1591892 TI - The Joe Doupe Young Investigator's Award. PMID- 1591893 TI - [Mechanism of the effect of serine and threonine on ammoniagenesis and biosynthesis of orotate in the mouse]. AB - We have evaluated the effects of serine and threonine on orotate metabolism in mice, by injecting i.p. 0.5 to 1.5 mmol/100 g of body weight, during 4 weeks of experimentation. The results indicate that serine as well as threonine cause a significant increase (p less than 0.01) of plasma ammonia and urinary orotate. We have also studied the effects of various inhibitors, adenine (0.3% diet), N (phosphonoacetyl)-L-aspartate (PALA) (10 mg/100 g, i.p.), acivicin (1 mg/100 g, i.p.) and cycloheximide (1.5 mg/kg, i.p.) on orotate synthesis in mice injected with serine (2.5 mmol/100 g, i.p.) or threonine (1.25 mmol/100 g, i.p.). The results show an increase (p less than 0.05) of urinary orotate following an adenine-rich diet, and a reduction of orotate following PALA (p less than 0.01). The orotic aciduria remained insensitive to acivicin while it was inhibited by cycloheximide. These results suggest that adenine blocks the utilisation of orotate and consequently could affect the biosynthesis of pyrimidines; the induction of orotate by serine and threonine is controlled by the translation of a specific protein synthesis, and necessarily implicates the mitochondrial carbamyl phosphate synthetase-I (CPS-I). The regulating step in this synthesis of orotate could also be the transport of carbamyl-phosphate from the mitochondria to cytosol. PMID- 1591894 TI - Response to initial therapy and new onset as predictors of prognosis in patients hospitalized with congestive heart failure. AB - Clinical predictors of in-hospital fatality were assessed in 191 persons admitted to the Yale-New Haven Hospital Intensive Care Unit with a diagnosis of congestive heart failure. In the 17 (8.9%) patients who died, the most important individual predictors among the presenting clinical features were absence of dyspnea, presence of anterior chest pain or jugulovenous distension, and cardiac severity due to ischemia, valvular disease, or arrhythmia. Two important predictors, largely neglected in previous literature, were a prior history of congestive heart failure and a poor clinical response after 24 h of therapy. Multivariable analysis led to the identification of 6 features (age greater than 70 y, prior history of congestive heart failure, jugulovenous distension, chest pain, cardiac severity, and poor early response to therapy) that could be combined into a simple clinical predictive index. The new index identified 5 prognostic groups with fatality rates of 0, 3.5, 7.4, 19.2, and 85.7 percent. An advantage of the clinical index is the identification of a subgroup of patients, with low risk for fatality, who may not need prolonged treatment in an intensive care unit. PMID- 1591895 TI - The relation between triglyceride synthesis in peripheral tissues and postprandial plasma triglyceride levels: preliminary evidence of a role for acylation stimulating protein. AB - The present study examines the hypothesis that the rate at which peripheral tissues synthesize triglycerides is a key determinant of the rate at which they are removed from plasma. The cells of greatest interest in this regard would, of course, be the adipocytes. However, serial sampling of this tissue is not possible in man. We have approached the question indirectly, by studying triglyceride synthesis in human mononuclear cells before and after an oral fat load. In addition, plasma levels of Acylation Stimulating Protein (ASP) were measured after an overnight fast and 4 h after ingestion of the oral fat load. Similar measurements were made in the same subjects after fasting overnight and with the fast extended for 4 additional hours. With the extended fast, no parameter measured changed significantly. However, after the oral fat load, the following changes were found to be significant: plasma triglycerides increased (63.6 +/- 31.1 vs 101.5 +/- 43 mg/dl, p less than 0.005) as did d less than 1.006 g/ml triglycerides (42.3 +/- 22.8 vs 78.0 +/- 39.7 mg/dl, p less than 0.005) and plasma ASP (10.4 +/- 2.2 vs 14.7 +/- 2.3 mg/dl, p less than 0.005). In addition, the rate of triglyceride synthesis in the mononuclear cells increased significantly (1.22 +/- 0.3 vs 1.52 +/- 0.3 nmol oleate/mg cell protein per h, p less than 0.005). There was also a significant inverse relation between the increase in the d less than 1.006 triglycerides between 0 and 4 h and the increase in triglyceride synthesis in the mononuclear cells (r = 0.91, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591897 TI - Glycine toxicokinetics: vitreous fluid concentration and visual impairment. AB - We report the results of kinetic experiments in sheep. Following systemic loading with 45 g glycine, plasma, cerebral spinal fluid (CSF), and vitreous fluid from the vitreous body of the eye were assayed for glycine concentrations. Mean baseline plasma, CSF, and vitreous glycine concentrations were 730, 46, and 191 mumol/L respectively. One hour after loading, values were 21292, 1103, and 1150 mumol/L respectively. During the succeeding 7 h plasma and CSF concentrations fell in parallel but remained above normal. In contrast the vitreous concentrations remained high and did not change significantly during the 7 h post infusion period. Retinal glycine receptors may be particularly vulnerable to neurotoxic effects of glycine because of these pharmacokinetic properties. PMID- 1591896 TI - T lymphocyte modification with the UTA microporous polyurethane vascular prosthesis: in vivo studies in rats. AB - Sequential quantification of blood T cell subsets by immunocytofluorometry was used to investigate the immune response of microporous polyurethane vascular prostheses after intraperitoneal implantation in rats. The experimental prosthesis, as developed by the University of Texas-Arlington group (UTA), and the Mitrathane prosthesis, as developed by Matrix Med., were implanted for 1, 2 and 6 weeks and compared with ePTFE and wounded rats without prostheses (control group). The implants were examined for histopathology by light microscopy. The percentages of CD4-(helper) and CD8-(suppressor) bearing cells of the PTFE group were significantly lower (p less than 0.05) than the control group 1 week post implantation. The UTA and the Mitrathane grafts exhibited a significant decrease in both T cell subsets at 1 week, and CD4-bearing cells at 2 weeks. At 6 weeks, T cell subsets were similar among all groups. The ratio of CD4/CD8- cells was similar among all groups except for the PTFE group, which was lower than the control group after 1 week. Histological examination of Mitrathane and UTA grafts showed an acute phase of inflammation which lasted at least 2 weeks. Some foreign body giant cells (FBGC) were present 2 weeks post-implantation, and encapsulation was greater than that observed with PTFE grafts. On the other hand, PTFE grafts exhibited a different pattern of inflammation compared to polyurethane grafts. PTFE implants exhibited a moderate chronic inflammatory response for the first week, as shown by the formation of FBGC. At 2 and 6 weeks, the grafts were encapsulated by a thin layer of collagenous tissue and FBGC were still present around the implants, mostly located in contact with the reinforcing mesh.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591898 TI - The hydrocarbon breath test in the study of lipid peroxidation: principles and practice. AB - Lipid peroxidation has gained increasing interest in recent years as one of the more prominent features of free radical-induced damage in biology. The study of lipid peroxidation might increase our understanding of the etiology and pathophysiology of a great number of diseases. Ethane and pentane are among the numerous end-products of lipid peroxidation and although they represent only a small and possibly variable proportion of the total amount of peroxidized polyunsaturated fatty acids, their determination in head space or exhaled breath enables accurate assessment of oxidative stress both in vitro and in vivo. To date, the number of studies utilizing the hydrocarbon breath test as a marker of lipid peroxidation in humans is small. Technical difficulties are among the main reasons for the limited use of this method. An appropriate washout period, the use of the right materials, the scrupulous avoidance of air contamination, adequate preinjection concentrations of the samples, and a sensitive gas chromatographic technique enable the accurate and reproducible measurement of hydrocarbons in human breath. The hydrocarbon breath test provides a noninvasive and extremely sensitive instrument for the assessment of oxidative stress status in adults as well as in children. PMID- 1591899 TI - Persistent hyperkalemia in a patient with diabetes mellitus: a reversible defect in kaliuresis during bicarbonaturia. AB - The purpose of this report is to apply recent advances in the understanding of the physiology of the excretion of potassium to a patient who had hyperkalemia due to a low rate of excretion of potassium. The defect was first suspected during therapy for diabetic ketoacidosis, when the concentration of potassium in plasma was unusually high (7.3 mmol/l) on admission and the deficit of potassium, as judged from the quantity of potassium infused to maintain normokalemia (40 mmol/24 h), was much less than expected. After recovery from diabetic ketoacidosis, hyperkalemia persisted despite near-normal values for creatinine and glucose in plasma. Excretion of potassium was low, considering the stimulus of hyperkalemia, and did not rise appreciably after the acute or chronic administration of a mineralocorticoid. The transtubular potassium concentration gradient (TTKG) did not exceed 6 after a large dose of fludrocortisone (200 micrograms) was administered. Notwithstanding, the TTKG rose to 14.4 following the intake of acetazolamide. We speculate that the basis for the hyperkalemia was type II hypoaldosteronism. PMID- 1591900 TI - Discordance of airflow limitation and ventilatory inhomogeneity in asthma and cystic fibrosis. AB - Although it is known that both airflow rates and gas distribution are impaired in asthma and cystic fibrosis (CF), the concordance of the change in these defects between two points in time has not been studied. On two separate occasions, the FEV1, FVC and slope of Phase III (SBN2/L%) of the single breath nitrogen test were determined, as well as the concordance between the change in these indices in 14 healthy subjects, 14 subjects with asthma, and seven subjects with CF. The coefficient of variation within a test session averaged less than 5% for the FEV1 and less than 10% for the SBN2/L% within each group. The change in FEV1 correlated with the change in FVC in all three groups, but did not correlate with the change in SBN2/L% in any group. In seven of the 14 cases of asthma and six of the seven cases of CF (outliers), the differences in the indices (expressed as the change in percent predicted) were greater than the differences observed in the control group. In three of the asthmatic and four of the CF outliers, the changes were as predicted, that is, both tests returned toward normal, or both became more abnormal. In two of the asthmatic and CF outliers both the FEV1 and SBN2/L% increased, while both decreased in the other two asthmatic outliers. Although some of the same factors will affect both indices, a worsening of ventilation inhomogeneity, which will affect the SBN2/L%, could occur with an improvement in ventilatory flow rate. Alternatively, airflow limitation could worsen but be accompanied by an improvement in ventilation homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1591901 TI - Cross-linguistic regularities in the frequency of number words. AB - We examine the frequency of numerals and ordinals in seven different languages and/or cultures. Many cross-cultural and cross-linguistic patterns are identified. The most striking is a decrease of frequency with numerical magnitude, with local increases for reference numerals such as 10, 12, 15, 20, 50 or 100. Four explanations are considered for this effect: sampling artifacts, notational regularities, environmental biases and psychological limitations on number representations. The psychological explanation, which appeals to a Fechnerian encoding of numerical magnitudes and to the existence of numerical points of reference, accounts for most of the data. Our finding also has practical importance since it reveals the frequent confound of two experimental variables: numerical magnitude and numeral frequency. PMID- 1591902 TI - The long-term modality effect: in search of differences in processing logographs and alphabetic words. AB - The visual superiority effect (a reverse long-term modality effect) has been consistently found with Chinese logographs. For its explanation in terms of script differences, it has been believed that lexical access is more direct or quicker for Chinese logographs than for alphabetic words. It has also been believed that Chinese logographs are more unique in shape or more discriminable than alphabetic words. Finally, Chinese logographs have been considered to facilitate recall through their graphic features that classify Chinese words into categories. The results of Experiments 1-5 show that these three assumptions can be ruled out. The results of Experiments 6-10, on the other hand, support the long-term priming interpretation of the visual superiority effect, which explains (a) why the visual superiority effect can be consistently obtained for recall of Chinese words by Chinese subjects, (b) why the effect cannot be consistently obtained for recall of English words by Western subjects, (c) why the effect can be also obtained for recall of English words by Chinese subjects, (d) why the effect can be easily obtained for recall of a set of words, but not for recall of a different set of words by Chinese subjects, and (e) why the effect can be easily obtained from Chinese subjects speaking a dialect that is different from Mandarin. PMID- 1591903 TI - Finger movements in braille reading: the effect of local ambiguity. AB - The hand movements of blind readers were recorded while they read sentences containing temporary local ambiguities, designed to induce garden path effects upon disambiguation. A syntactically ambiguous beginning ("The spy saw the cop with ... ") was compatible with attachment of the following prepositional phrase (PP) either to the verb ("saw") or the noun ("cop"), but the content of the PP was inconsistent with verb phrase attachment in NPA sentences ("with a revolver"), not in VPA sentences ("with binoculars"). Mean total scanning time per character increased in the PP region of NPA sentences, not of VPA sentences. The effect, however, depended on both the content of the PP and its predictability, and was significant by items only when both factors favoured VPA. The slowing down over the PP was entirely due to increased incidence of regressions to that region, and first-pass scanning speed was unaffected by sentence type. In studies with visual reading, disambiguation has been found to have a large effect on first-pass scanning. The results confirm previous suggestions that regressions are the main repair device available to the braille reader to cope with local increases in processing load. PMID- 1591904 TI - Perception, ontology, and naming in young children: commentary on Soja, Carey, and Spelke. PMID- 1591905 TI - Alexithymia and the five-factor model of personality. AB - The relationship between alexithymia assessed by the Toronto Alexithymia Scale (TAS) and the five-factor model of personality measured by the NEO Five-Factor Inventory (FFI) was investigated in a group of psychiatric outpatients (n = 114) and normal volunteers (n = 71). When controlling for depression, the domains of neuroticism, introversion, and low openness predicted alexithymia. These three dimensions accounted for 57.1% of the explained variance in the patient cohort and 38.1% in the volunteer group. In the patient cohort, neuroticism contributed the majority of explained variance, which may reflect the state effect of distress that elevates neuroticism. Introversion was the most significant predictor in the volunteer group. These data suggest alexithymia is a unique personality trait that is not fully explained by the five-factor model of personality. PMID- 1591906 TI - Evaluation of the reported association of obsessive-compulsive symptoms or disorder with Tourette's disorder. AB - This review evaluates the evidence reporting an association of obsessive compulsive symptoms (OCS) and obsessive-compulsive disorder (OCD) with Tourette's syndrome or disorder (TS). Published reports in the literature describing a relationship between OCS-OCD and TS provided the data for the review. The methodological adequacy of the studies are discussed and rated on five criteria: adequacy of the experimental sample, presence and adequacy of the control sample, whether tics are defined as OCS-OCD, whether blind procedures are used to diagnose OCS-OCD in subjects and controls, and evidence for the reliability and validity of OCS-OCD measures. Although there are considerable clinical indications suggesting an association of OCS-OCD with TS and chronic motor tic disorder (CMT), and a possible overlap between OSC-OCD and TS, our evaluation of the evidence does not provide adequate support for an association between these disorders. To meaningfully evaluate the possible relationship between OCS-OCD and TS requires development of specific criteria for classification of OCS-OCD-TS symptoms, use of adequate experimental and control samples, blind evaluation, reliable and valid measures of OCS-OCD-TS, and appropriate statistical analysis. If such studies are performed, it is possible that the strong relationship reported between OCS-OCD and TS is more likely to be artifact than fact, and recent bandwagon effect rather than the latest breakthrough. PMID- 1591907 TI - Belief and behavior: the role of "folk psychology" in psychiatry. AB - Most psychiatrists assume that belief is a basis for behavior. The validity of this assumption has been challenged by certain philosophers who assign the concept belief to the domain of "folk psychology." These philosophers contend that the discoveries of neuroscience will eliminate the ideas of folk psychology from scientific discourse and that behavior will eventually be accounted for in terms of brain states. In order to examine the relationship of belief and behavior, examples of self-mutilation by normal and abnormal individuals are reviewed. It is concluded that belief is a basis for behavior and that neuroscience, like folk psychology, is valid only within certain limits. PMID- 1591908 TI - Prediction of intravenous drug use. AB - Information about lifetime intravenous drug use (IVDU) was obtained from 1,062 relatives of hospitalized alcoholics, felons, and control subjects, of whom 92 had a history of IVDU and an additional 230 had a history of substantial, but non IV drug use. The IVDUs were significantly more likely than all other subjects to have reported experiencing numerous behavioral and social difficulties relating to conduct difficulties, early initiation of substance use, and disrupted living situation before the age of 15. They were also more likely to have exhibited conduct problems than other drug users. In multivariate analyses, four symptoms (fighting in school, juvenile arrest, initiation of cannabis use before 15, or initiation of sexual activity before 15) differentiated IVDUs. A history of greater numbers of these problems was associated with increasing risk for IVDU, both when compared with the total sample and when compared with other drug users. PMID- 1591909 TI - Consumers' attitudes toward DSM-III and DSM-III-R: a 1989 survey of psychiatric educators, researchers, practitioners, and senior residents. AB - To understand how DSM-III and DSM-III-R are used and perceived by educators, researchers, practitioners, and trainees, in the spring of 1989 we surveyed all US psychiatric residency training directors (N = 197), 337 active psychiatrist researchers, a nationwide random sample of 952 practicing psychiatrists, and all PGY-3 and -4 residents. We describe the factors influencing the use of DSM-III and DSM-III-R and the perceptions of strengths and weaknesses of the DSMs from various perspectives (training, research, and practice). A modest increase in the acceptance of the DSM system was noted in comparing the results from the current survey and a similar 1984 survey about DSM-III. The implications of these findings for the development of DSM-IV are discussed. PMID- 1591910 TI - Cognitive and perceptual distortions in borderline personality disorder and schizotypal personality disorder in a vignette sample. AB - Clinical vignettes of patients with borderline personality disorder (BPD) and schizotypal personality disorder (STPD) were evaluated and rated for evidence of cognitive and perceptual distortions. The differences in the distortions of each group were then compared. The findings show that while STPD patients have significantly more cognitive and perceptual distortions than borderlines, there is an abundance of such distortions in the borderline group. The borderline group may differ, moreover, in that their cognitive and perceptual distortions were found to be significantly more object-related than those of the schizotypal group. PMID- 1591911 TI - Vulnerability to drug abuse among opioid addicts' siblings: individual, familial, and peer influences. AB - Vulnerability to drug abuse was explored among 132 siblings of opioid-addicted probands. Multiple risk factors at the levels of the individual, family, and peer group were examined, including sensation-seeking, teenage experimentation with drugs, ordinal position in the family relative to the addicted proband, birth order, and the extent to which peers used drugs and offered drugs to the individual during adolescence. Risk factors were assessed via questionnaire and interview data, while diagnoses of adult drug abuse were derived from structured interviews. Early experimentation with drugs was found to be a powerful risk variable: siblings who had tried drugs as teenagers were almost five times as likely as others to be drug abusers as adults. Other significant correlates of adult drug abuse included sensation-seeking and drug use among the adolescent peer group. Results of the study are discussed in terms of implications for preventive intervention in the field of substance abuse. PMID- 1591912 TI - A psychoeducational and support group for obsessive-compulsive disorder patients and their significant others. AB - This report details the contents of a 10-week psychoeducational and support group for obsessive-compulsive disorder (OCD) patients and their significant others. As growing numbers of OCD patients seek behavioral and psychopharmacologic treatments for their disorder, the need for such a group has increased. Little is written about this type of group, despite the need. Successful research and evaluation of this treatment entity will rely on a clearly defined group protocol such as the one reported here. In the present study, the group averaged 21 members in attendance. The 17 members present at the final session rated the group an average of 3.8 on a 0 (poor) to 4 (excellent) scale across several content areas. These uncontrolled data suggest that the format has clinical utility as a tool for the delivery of information and support to OCD patients and their significant others. PMID- 1591913 TI - Positive versus negative schizophrenia and basic symptoms. AB - In a sample of 71 Research Diagnostic Criteria (RDC) schizophrenic patients, the relationship among the basic symptoms measured by the Frankfurt Complaint Questionnaire and Andreasen and Olsen's types of schizophrenia was studied. The results do not support an overlap between negative and basic symptoms; rather, basic symptoms appear to be more frequent in patients with positive symptoms. Basic symptoms were consistently correlated to formal thought disturbances, but the values were only moderate (r = .3). PMID- 1591914 TI - Psychoactive substance use disorder in relatives of patients with anorexia nervosa. AB - We assessed the lifetime prevalence and morbid risk of psychoactive substance use disorder (SUD; alcoholism and drug use disorder) in the first- and second-degree relatives, excluding children, of 34 female patients with anorexia nervosa (AN) and 34 age- and sex-matched controls who had no history of an eating disorder. Diagnoses of relatives were made blind to probands' diagnoses. The prevalence of SUD was 9% in both anorectic and control relatives, and the figures for morbid risk were 14% and 15%, respectively; these differences were nonsignificant. These results suggest that adolescent and adult women with AN do not possess many of the familial factors that predispose to the development of psychoactive SUD. PMID- 1591915 TI - Sleep electroencephalographic patterns and cranial computed tomography in anxiety disorders. AB - Sleep electroencephalogram (EEG) and cranial computed tomography (CT) were performed in 15 drug-free inpatients with an anxiety disorder. The sleep EEG of the patients was characterized by a decreased sleep efficiency and a shortened REM latency. Under visual inspection, four (27%) patients showed ventricular enlargement, while an increased ventricular brain ratio (VBR) was measured in five (33%). No clear associations between EEG sleep measures and ventricular size became obvious, although there is good evidence in the literature that sleep continuity, slow-wave sleep, or REM sleep are closely related to ventricular and/or sulcal widening in various neuropsychiatric disorders. PMID- 1591916 TI - Panic and agoraphobia's sequence of improvement during pharmacotherapy. PMID- 1591917 TI - Barrier methods of contraception and cervical intraepithelial neoplasia. AB - This North Carolina-based case-control study examined risk factors for cervical intraepithelial neoplasia (CIN). Cases were 103 women with biopsy-confirmed CIN II or III who were recruited from a referral dysplasia clinic. Controls were 258 family practice patients with normal cervical cytology. All subjects were interviewed regarding their sexual and reproductive history, Pap smear screening, active and passive cigarette exposures, and contraceptive use patterns. When compared with controls, cases were half as likely to have ever used barrier methods of contraception; the adjusted odds ratio was 0.5 (95% CI 0.2-0.9). The risk of CIN II/III decreased further with increasing years of barrier method use. Recency, latency, and age at first barrier method use were all associated with a reduced risk of CIN. Men and women should carefully consider the range of benefits of barrier method use as a means to reduce their risk of unwanted pregnancies, sexually transmitted diseases, and cervical neoplasia. PMID- 1591918 TI - Condom performance during vaginal intercourse: comparison of Trojan-Enz and Tactylon condoms. AB - Forty-nine mutually monogamous couples used a total of 478 condoms during vaginal intercourse in a prospective trial whose purpose was to discover whether the performance of a new non-latex hypoallergenic condom was substantially equivalent to that of a leading condom brand already being marketed. Of these 478 condoms, seven (1.46%) either broke or fell off the penis during intercourse. Two (0.42%) of the 471 condoms that did not break or fall off during intercourse fell off the penis when it was being withdrawn from the vagina. Altogether, 469 (98.1%) of the 478 condoms used for intercourse survived intact throughout intercourse and withdrawal. Differences in breakage and slippage rates for the two condom brands were statistically insignificant. The overall 98.1% success rate is much higher than the rate of success found in a previous condom trial with nearly identical research protocol. The reason for the difference is attributed to much more precise questioning of subjects in the current trial. PMID- 1591919 TI - Lipid metabolism in Norplant-2 users--a two-year follow-up study. Total cholesterol, triglycerides, lipoproteins and apolipoproteins. AB - Changes in lipid metabolism in 25 healthy female volunteers during a 24-month application of Norplant-2 were evaluated in an open clinical trial. Total serum cholesterol decreased significantly (p less than 0.05/p less than 0.05) by 10%/9% after 12 months and by 3%/7% (n.s./n.s.) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). Serum triglycerides decreased by 34%/28% (n.s./p less than 0.05) after 12 months and by 29%/25% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). HDL-cholesterol decreased significantly by 18%/12% (p less than 0.01/p less than 0.05) after 12 months and by 12%/12% (p less than 0.05/p less than 0.05) after 24 months of Norplant-2 use (all subjects/subjects completing 24 cycles). No statistically significant difference between serum levels of LDL cholesterol prior to and after 12 and 24 months of Norplant-2 use could be found. VLDL-cholesterol levels decreased significantly by 38%/38% (p less than 0.05) after 12 and by 25%/25% after 24 months of Norplant-2 application (p less than 0.01) (all subjects/subjects completing 24 cycles). Apolipoprotein Al decreased significantly by 23%/23% (p less than 0.001/p less than 0.01) after 12 and by 21%/22% after 24 months of Norplant-2 application (p less than 0.01/p less than 0.01) (all subjects/subjects completing 24 cycles). No statistically significant difference between apolipoprotein All levels prior to and after 12 and 24 months of Norplant-2 implantation could be found. Apolipoprotein B decreased significantly by 27%/17% (p less than 0.05/p less than 0.05) after 12 months of Norplant-2 application (all subjects/subjects completing 24 cycles). The decline after 24 months of Norplant-2 use was not significant. Changes in lipid metabolism caused by oral hormonal contraceptives differ in the various clinical trials; however, most investigators found that serum levels of total cholesterol and triglycerides increase under the application of OCs. Contrary to this, a decrease of total cholesterol and triglycerides under Norplant-2 use was noted. Furthermore, we found a significant decrease of lipoproteins and apolipoproteins- with the exception of LDL-cholesterol and apolipoprotein All, which did not show any significant modifications. Thus, Norplant-2 seems to be non-contributory to cardiovascular risk and might even provide protection against such risks. PMID- 1591920 TI - Acceptability of Norplant implants for fertility regulation in Singapore. AB - The continuation rate at the end of this five-year clinical study was 60% with no accidental pregnancy occurring throughout the five years. The post-removal conception rate in women desiring pregnancy was 92% at the end of two years. The majority of acceptors described the overall experience with the implants as favourable. In fact, 75% of the women planning to use contraception after removal of the implants were going to use implants again. PMID- 1591921 TI - Contraception with subdermal implants releasing the progestin ST-1435: a dose finding study. AB - A new modified subdermal implant releasing the potent progestin ST-1435 was studied in eleven fertile-aged women. These implants have been developed for contraception and they have a life-time of two years. Three implant lengths of 4, 6 and 8 cm were tested to find the optimal steroid dose for inhibition of ovulation. Serum samples were collected twice per week during a six-week period every six months. The concentrations of serum ST-1435, estradiol and progesterone were determined by RIA. Ovulation was inhibited by all ST-1435 doses tested. The concentration of serum progesterone was below 6 nmol/l in all samples tested showing the absence of luteinization. The concentration of serum ST-1435 increased with increasing ST-1435 dose. Serum estradiol concentrations were quite variable, showing wide range and occasional high peak values typical of progestin treatment; the mean value of serum estradiol concentrations measured did not differ with different ST-1435 doses. The results of steroid determinations led to the conclusion that a single 4 cm subdermal implant is optimal for contraception. With this dosage level, ovulation is inhibited and side effects are minimized. Bleeding control was variable. No hormonal side effects due to the progestin ST 1435 were reported. This method, using a single 4 cm subcutaneous implant releasing the progestin ST-1435 with a life-time of two years, represents a promising alternative for inhibition of ovulation and contraception. PMID- 1591922 TI - Is the contraceptive effect of 300 micrograms of norethisterone mainly peripheral or central? AB - The effect of norethisterone (NET) on pituitary function was evaluated by measuring circulating follicle stimulating hormone (FSH) and luteinizing hormone (LH) during the mid follicular phase as well as before and after removal of the corpus luteum (CL) in 30 untreated women and 43 women treated with 300 micrograms of NET daily for three months. All untreated women exhibited significantly elevated FSH levels after removal of the CL irrespective of the stage of the luteal phase. In the NET-treated women, the levels of FSH were significantly raised in women with luteal activity but these levels were not influenced by the operative procedure in those women without luteal activity. The LH levels remained unchanged after removal of the CL in both untreated and NET-treated women. The results suggest that a low dose of gestagen exerts variable effects on pituitary function. The main contraceptive effect seems to be through direct interference with ovarian function. PMID- 1591923 TI - Relationships between pelvic pain and prostaglandin levels in plasma and peritoneal fluid collected from women after sterilization. AB - Prostaglandin levels in plasma and peritoneal fluid were determined in 10 sterilized women with pelvic pain without pathological findings. Another 15 healthy women were regarded as controls. The 6-keto-PGF1 alpha levels in peritoneal fluid collected from patients with pelvic pain were significantly higher than that from the controls (p less than 0.05). The results indicated that prostaglandins might play an important role in pelvic pain following sterilization. PMID- 1591924 TI - Contraception after heart surgery. AB - This study represents the different methods of contraception used by women having cardiac surgery at Ain Shams University Hospital. The study comprised of 250 women having had mitral commissurotomy, 77 women having had valve replacement including one case of triple valve repair and 3 women having had cardiac surgery for congenital heart disease. An IUCD was used by 170 women (51.5%), vaginal tablets by 4 women (1.2%), oral contraceptive pills by 7 women (2.1%), "safe period" by 7 women (2.1%), tubal ligation was performed in 10 women (3%). The husbands of 33 women (10%) used condoms, and 99 women (30%) did not use contraceptive methods. The IUCD was tolerable and was associated with bleeding in 60 women (35.2%) and leucorrhoea in 55 (32.3%). The IUCD was removed from only one woman due to severe bleeding. Three pregnancies occurred with condom users in two women who had had mitral commissurotomy and one having had valve replacement. There was no case of bacterial endocarditis in the study group. PMID- 1591925 TI - CDRI-85/287, a novel antiestrogen and antiimplantation agent: biological profile and interaction with the estrogen receptors in immature rat uterus. AB - Postcoital antifertility efficacy, estrogenic and antiestrogenic activities of compound 85/287 were determined by the subcutaneous route in rats. It was 100% effective in preventing implantation at 0.5 mg/kg dose when administered within 24 h of mating and at 0.05 mg/kg in the days 1-5 post-coitum regimen. In the immature rat bioassay, it exhibited mild uterotrophic effect at the contraceptive dose but when administered along with estradiol (E2), it caused almost complete inhibition of uterine weight gain and vaginal cornification at the 2 mg/kg dose. E2 administration to immature rats (0.1 microgram, s.c., 3 days) caused 3-5 fold increase in the nuclear as well as cytoplasmic estradiol receptor (ER) content as compared to controls. In contrast, 85/287 (0.5 mg/kg and 2 mg/kg; s.c.), only translocated the ER to the nuclear compartment resulting in a depletion of cytoplasmic ER levels. Concurrent administration of 85/287 and E2 inhibited E2 induced increase in cytoplasmic ER. It is suggested that compound 85/287 exerts its antiestrogenic and antiimplantation action by interfering with the formation of E2-receptor complexes in the uterus. PMID- 1591926 TI - 3NTPT: a newly discovered antifertility agent. V. Ovarian dysfunction in Dysdercus koenigii. AB - A 4 h exposure to a residual film of 15 mg 1-(3-nitrophenyl)-4,4,6-trimethyl 1H,4H-pyrimidine-2-thiol (3NTPT) dissolved in 5 ml acetone significantly inhibited ovarian growth in Dysdercus koenigii. The ovaries of treated females remained small and the trophocytes, the trophic core, the prefollicular tissue and the oogonia completely degenerated. This was followed by degenerative changes in the follicular epithelium, the interfollicular tissue and the developing oocytes. Resorption of the oocytes reduced the vitellarium to an empty tube. The follicular epithelium of the resorbed oocytes protruded into the lumen, while the interfollicular tissue completely degenerated. By day 7 after treatment, the ovaries were completely dystrophic, and this state was not reversible. PMID- 1591927 TI - Effect of elastin peptides on the activities of antioxidant enzymes in fibroblasts. AB - The effect of elastin peptides (kappa-elastin) was investigated on murine fibroblasts. The data indicate that elastin peptides increase the activities of antioxidant enzymes detoxifying free radicals and increase the lipid peroxide concentration within the cell. These results suggest that the influence of elastin peptides on oxygen metabolism may be related to their activities in vivo following elastin degradation and can contribute to their role in the pathogenesis of atherosclerosis. PMID- 1591928 TI - Balbiani rings in Drosophila: the Balbiani ring 1 is a common characteristic in several montium species. AB - Drosophila bicornuta, D. jambulina, D. biauraria, D. triauraria and D. quadraria, belonging to the montium subgroup of the melanogaster species, have a well-formed Balbiani ring (BR) in their salivary gland chromosomes. The BR has many similarities to the BR1 of D. auraria and D. serrata, two other montium species, indicating that the BR1 is a common characteristic in several species of the montium subgroup. It is suggested that the BR1 structure and its possible function(s), in contrast to the BR2, may have been selected during evolution. PMID- 1591929 TI - The rising problems of asthma; mechanisms and management. PMID- 1591930 TI - NIAID programs for asthma research, education, and outreach. PMID- 1591931 TI - The National Heart, Lung and Blood Institute asthma program. PMID- 1591932 TI - Inner-city asthma. The epidemiology of an emerging US public health concern. PMID- 1591933 TI - Asthma among minority children. A growing problem. PMID- 1591935 TI - The role of allergens in asthma. PMID- 1591934 TI - Mechanisms of airway inflammation. PMID- 1591936 TI - The relationship of viral respiratory infections and asthma. PMID- 1591937 TI - Diagnosis and classification of asthma. PMID- 1591938 TI - Physiologic evaluation of asthma. PMID- 1591939 TI - Potentially fatal asthma. PMID- 1591940 TI - Goals in the management of asthma. PMID- 1591941 TI - Intense pharmacotherapy. PMID- 1591942 TI - Psychiatric aspects of asthma. PMID- 1591944 TI - Problem cases in asthma and problems in asthma management. PMID- 1591943 TI - Effect of racial and socioeconomic factors on asthma mortality in Chicago. PMID- 1591945 TI - An alkaloid, cepharanthine, potentiates the bactericidal effect of methylglyoxal bis (cyclopentylamidinohydrazone) on Staphylococcus aureus. AB - Antiproliferative effects of combined treatment with methylglyoxal bis(cyclopentylamidinohydrazone) (MGBCP), a polyamine biosynthesis inhibitor, and cepharanthine, a biscoclaurine alkaloid, on methicillin- and gentamicin-resistant Staphylococcus aureus were investigated. The bactericidal effect of MGBCP on S. aureus was potentiated by the cepharanthine treatment. Cellular polyamine levels of the bacteria treated with both MGBCP and cepharanthine were much lower than those of the bacteria treated with MGBCP alone. On the contrary, the cellular MGBCP concentration was much higher in the cepharanthine-treated bacteria. Thus, cepharanthine was considered to enhance the incorporation of MGBCP into the bacteria. The combination of MGBCP and cepharanthine resulted in greater suppression of macromolecular synthesis in the bacteria that might have caused greater suppression of bacterial growth. PMID- 1591946 TI - In vitro susceptibility of yeast isolates from the blood to fluconazole and amphotericin B. AB - 221 yeast strains including 131 of Candida albicans, 21 of C. tropicals, 23 of C. parapsilosis, 19 of C. glabrata, 7 of C. guilliermondii, 6 of C. krusei and of other species were isolated from the blood. The activity of fluconazole and amphotericin B was investigated by means of a photometer-read broth microdilution method measuring the 30% inhibitory concentrations (IC30). The results of fluconazole showed a higher susceptibility of C. albicans compared to the other species. However, 6 (4.5%) resistant strains of C. albicans were found. Low sensitivity and resistance were evaluated for C. krusei and C. glabrata strains. All isolates showed susceptibility to amphotericin B. PMID- 1591947 TI - Oxygen-derived free-radical scavengers prolong survival in colonic cancer. AB - The influence of scavengers of oxygen-derived free radicals on survival in colonic cancer was studied. Following curative surgery for carcinoma of the sigmoid colon at Dukes' stage C, 198 patients making an uneventful recovery from surgery were randomized to the control group or to receive allopurinol (50 mg orally 4 times a day) or dimethyl sulphoxide (DMSO, 500 mg orally 4 times a day). In 144 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p less than 0.01) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals, suggest that these radicals are implicated in the detrimental effects of malignancy and that removing them provides a survival advantage in patients bearing colonic carcinoma. PMID- 1591948 TI - Oxygen-derived free-radical scavengers prolong survival in gastric cancer. AB - The influence of oxygen-derived free radical scavengers on survival in gastric cancer, with serosal invasion and metastases to the lymph nodes surrounding the stomach, was assessed in a prospective randomized controlled double-blind trial conducted for 5 years. To this end, allopurinol (inhibits the enzyme xanthine oxidase which is responsible for the formation of superoxide radicals and scavengers hydroxyl radicals) and dimethyl sulphoxide (DMSO; scavengers hydroxyl radicals) were used. Following potentially curative distal two-thirds partial gastrectomy, 228 patients making an uneventful recovery from surgery were randomized to the control group or to receive allopurinol (50 mg by mouth 4 times a day) or DMSO (500 mg by mouth 4 times a day). In 160 fully evaluable patients who were studied for 5 years, allopurinol and DMSO incurred a significant (p less than 0.01) survival advantage over the whole period of study. The similarity in efficacy between allopurinol and DMSO and the fact that the only action they share is scavenging oxyradicals suggest that these radicals mediate the aggressiveness of gastric cancer by producing tissue damage, thus allowing the cancer to spread. Consequently, oxygen-derived free radicals are implicated in the mechanism of gastric cancer, and removing them provides patients with a survival advantage. PMID- 1591949 TI - Distribution of beta lactamases in Enterobacteriaceae: indoor versus outdoor strains. AB - The distribution of beta-lactamases of indoor and outdoor origin was studied over a 9-month period. We consecutively selected 37 indoor and 48 outdoor strains of the following genera of the Enterobacteriaceae family: Escherichia (species coli), Enterobacter, Proteus, and Klebsiella. All isolates were resistant to amoxicillin and/or cephalothin and/or cefamandole. All strains showed beta lactamase activity. We characterized the enzymes by an isoelectric focusing method and by a disc diffusion test. For both indoor and outdoor isolates we found that plasmid-mediated beta-lactamases were encountered mostly in the E. coli and Klebsiella species, whereas chromosomally mediated enzymes predominated in the Proteus and Enterobacter species. No significant difference in distribution of beta-lactamases could be found comparing both groups, but it was noted that chromosomally mediated beta-lactamases predominated in the Department of Urology, while plasmid-mediated beta-lactamases prevailed in other departments (p less than 0.05). PMID- 1591950 TI - Lipopolysaccharide alterations responsible for combined quinolone and beta-lactam resistance in Pseudomonas aeruginosa. AB - Resistant variants of three clinical Pseudomonas aeruginosa isolates were obtained in the presence of aztreonam. The variants exhibited a four- to eightfold increase in the minimal inhibitory concentrations to beta-lactam antibiotics (except imipenem) to quinolones, such as norfloxacin and fleroxacin, chloramphenicol and tetracycline, but not to gentamicin and polymyxin B. beta Lactamase production was barely detectable in both wild-type strains and the resistant clones. Only ampicillin, cefoxitin and imipenem increased the production of beta-lactamase, whereas various other beta-lactams did not. Penicillin-binding proteins remained unchanged in the aztreonam-resistant clones. The analysis of the outer membrane proteins did not reveal differences in the outer membrane proteins between the wild-type strains and the aztreonam-resistant clones. Two of the three antibiotic-resistant isogenic clones contained less lipopolysaccharides (LPSs) than their corresponding wild-type strains. Moreover, it could be demonstrated that the ratio of 2-keto-3-deoxy octonate to carbohydrate of the LPS changed in any case between the wild-type strains and the aztreonam-resistant clones. These alterations were accompanied by a decrease in surface hydrophobicity of the resistant clones as compared to the wild-type strains. Therefore, quantitative as well as qualitative alterations in the LPS may provide an explanation for the resistant phenotype observed. PMID- 1591951 TI - [Analysis of 20 cases of amitriptyline poisoning]. AB - 20 cases of amitriptyline poisoning have been reported. The main symptoms were come in different degrees, pupil dilatation, tachycardia, retention of urine. Raising of blood pressure and subnormality of body temperature appeared in part of patients. There were convulsive attacks in some severe patients. EKG were abnormal in half of patients. Besides gastric lavage and acceleration of excretion, using of physostigmine was one of the important reused steps, it often was the determinate factor to get success. Convulsive attack was the main dangerous to death. Some discussions have been made about relative problems. PMID- 1591952 TI - [Similarity of drug therapy between schizophrenia and their first degree relatives]. AB - 61 pairs of probands and their first degree relatives who suffered from schizophrenia and once admitted to our hospital were analyzed. And according to the drugs used 61 pairs of patients were divided into two groups: concordance and disconcordance group. Estimation of these patients with General Assembly Scale (GAS) and the result suggests that there is significant difference of treatment efficiency between the probands and their first degree relatives of disconcordance group (P less than 0.05), but there is no significant difference in concordance or control groups respectively (P greater than 0.05). It seems that clinicians can choose drugs for first degree relatives according to the efficiency of drugs which probands used. PMID- 1591953 TI - [A clinical research on mental disability of chronic schizophrenia. 202 cases report]. AB - 202 cases of chronic schizophrenia were investigated to determine the order of severity of mental disability. 112 cases were male and 90 cases were female. The average age of the cases was 51.7 +/- 3.4 years, the onset age of the disease was 22.9 +/- 6.9 years. In order to measure the severity, we worked out "Social Disability Screening Schedule for In-patients" (SDSS-I) based on "Social Disability Screening Schedule" offered by WHO. 202 cases were measured with SDSS I, the results showed that 6 cases were slight, 22 cases were mild, 66 cases were severe and 108 cases were profound. Most part of the cases (86.7%) were severely and profoundly mentally disabled. PMID- 1591954 TI - [Drug abuse among 4139 medical professionals: field survey, assessment of psychosocial status and analysis of risk factors]. AB - A cluster sampling survey among 4139 subjects was carried out to detect present trend of drug abuse of medical professionals. Higher prevalence rate (2.3%) was found compared with local residents in previous survey by the same authors. The drug of abuse of those positive cases are of the sedative-hypnotic type and benzodiazepine abused most predominantly. PSE, EPQ, reactive features of life events and SDSS were assessed to explore the clinical characteristics of the addicted cases. Adopting Logistic regression with interactive plus stepwise mode, risk factors were analysed. It was clearly revealed that all positive cases do coincide with the rule of iatrogenic drug dependency. PMID- 1591955 TI - [Anorexia nervosa with bulimia and self-provoked-vomiting (a case report)]. AB - A young female anorexia nervosa patient reported who was undigested with food, weight dropped to half of the normal standard. She manifested not only episodic bulimia, impulsive self-injury, suicidal attempt, and obvious depressive emotion; but also self-provoked-vomiting, wandering, stealing and lying. The course of disease lasted already three years, she got 37 points on Hamilton Depressive Scale. Positive DST and normal EEG were exhibited in lab tests. The patient was improved after comprehensive therapy for about 5 months and then discharged. The recent literatures were reviewed on epidemiology, etiology, clinic features, therapy, prognosis and its relationship with depression. PMID- 1591956 TI - [Long-term prognosis following cerebrovascular disease]. AB - A follow-up study on 885 cases of cerebrovascular disease who survived acute stage and were registered through prevalence survey in 1983, had been carried out for 5-8.5 years. The results shown that 34.58% died, 34.13% were independent and 31.29% needed help in various degrees. The older the age was, the worse the prognosis was. After 3, 5 and 8 years, the survival rates of the cases were 86.98%, 75.70% and 64.26% respectively, and all were lower than that in general population. The difference of survival rates between the ischemic cases and the hemorrhagic cases was not found. PMID- 1591957 TI - [The effect of hyperbaric oxygenation on prostaglandin I2 and thromboxane A2 during reperfusion for experimental cerebral ischemia in rabbits]. AB - Thirty three New Zealand rabbits were randomly divided into three groups, i.e. the control group, the high atmospheric pressure. (HAP) group and the hyperbaric oxygenation (HBO) group. The experimental animals were made into the models of reperfusion for acute incomplete cerebral ischemia. The blood-gas analyses drawn from the common carotid arteries and the internal jugular veins were carried out, and the 6-keto-PGF1a and TXB2 in the brain tissues determined. The results showed that the contents of 6-keto-PGF1a in the brain tissues of the HBO groups were significantly increased (P less than 0.01). While those of TXB2 were significantly decreased (P less than 0.01). The po2 in both the arterial and the venous blood were obviously elevated in the HBO group. Pathological examination showed that the brain tissue damages in the HBO group were the slightest among the three groups. It was postulated that the effect of HBO on 6-keto-PGF1a and TXB2 might reflect one of the mechanisms of HBO for the treatment of acute cerebral ischemia. PMID- 1591958 TI - [Cerebrospinal fluid (CSF) cytochemistry of acute cerebrovascular diseases with clear CSF: observation of nonspecific esterase activity of mononuclear phagocytes]. AB - CSF nonspecific esterase (ANAE) activities of mononuclear phagocytes of 35 patients with intracerebral hematoma (ICH) with clear CSF and 25 with cerebral thrombosis and 17 normals were observed. The ANAE activities of ICH were much higher than those of thrombosis significantly (P less than 0.01). Furthermore, the distributions of ANAE activities of all cases suggested that there were few overlaps between both diseases. The CSF cytochemical detection was obviously superior to routine CSF cytological examination in differentiating strokes with clear CSF. The authors concluded that these results provided a simple inexpensive and relatively accurate method to differentiate hemorrhagic from ischemic cerebrovascular diseases in case of without CT. PMID- 1591959 TI - [Tardy epilepsy--clinical analysis of 292 cases]. AB - 292 cases of tardy epilepsy were studied. 242 cases of them had undertaken CT scanning, these results were compared with the results of EEG the patients with local seizures or local abnormalities on EEG had a significantly high abnormality rate on the CT scans. In 114 cases (39%) the causes of the seizures were due to head injury, cerebrovascular disease, encephalitis or meningoencephalitis, brain tumor, or excessive alcoholic drinking. The authors were of the opinion that although no relation could be found between the history and abnormal findings on CT scans, the patients with tardy epilepsy should undertake CT scanning early. PMID- 1591960 TI - [Study of brainstem auditory evoked potentials in patients with vertebrobasilar blood supply insufficient]. AB - Brainstem auditory evoked potentials (BAEP) were studied in 93 patients with vertebrobasilar blood supply insufficient. The result showed that the abnormal rate of BAEP was 76.3%, and the rate of abnormality in acute period was much higher than that in recovery period. The BAEP types were classified as inner, brainstem and mixed. The vertigo could be caused by the inner ear ischemia, brainstem or both of them. If there is no improvement of BAEP in long-term follow up, it suggested that there should be the tiny infarction affecting auditory passage or subclinical blood supply insufficient in brainstem. We believe that BAEP is valuable for the diagnosis of vertebrobasilar blood supply insufficient. PMID- 1591961 TI - [Dopa-induced dyskinesia in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated hemiparkinsonian monkeys]. AB - Infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right common carotid artery of 5 rhesus monkeys produced hemiparkinsonian syndrome in the contralateral limbs which responded to madopa or apomorphine therapy. Moreover, these two drugs induced circling away from the MPTP-treated side, amphetamine induced rotation toward the MPTP-treated side. Long-term use of madopa developed a peak-dose dyskinesia of the face and the limbs contralateral to the MPTP-treated side. The ipsilateral toxic effects were confirmed biochemically by reduction of nigrostriatal DA and histologically by degeneration of nigral neurons of the MPTP-treated side. It is concluded that this hemiparkinsonian model of rhesus monkey will be of value in the elucidation of the neural mechanism underlying L-DOPA or DA agonist induced dyskinesia in Parkinson's disease and in the search for newer methods of treatment which would produce less dyskinesia and response fluctuations. PMID- 1591962 TI - [An investigation on changes in blood CuZn-superoxide dismutase contents in type I, II schizophrenics]. AB - Blood CuZn superoxide dismutase (CuZn-SOD) changes during neuroleptic drugs treatment were measured by means of double-antibody immunoradiometric assay, in 121 schizophrenics (77 cases with Type I and 44 cases with Type II), and 128 normal subjects as control group. The results revealed: (1) before treatment, the overall blood content of CuZn-SOD in patient group showed higher significantly than that of control group (t = 12.34, P less than 0.001); (2) the content of CuZn-SOD in Type I schizophrenics was higher than that of Type II (t = 13.93, P less than 0.001); (3) after treatment, the CuZn-SOD content decreased obviously in Type I (t = 7.715, P less than 0.001), while no significant change in Type II was encountered (t = 0.541, P less than 0.05). The pathophysiological mechanisms of dopamine-Oxygen free radicals relating to the Type I and Type II schizophrenics was discussed briefly. PMID- 1591963 TI - [A control study of intravenous versus oral clomipramine in major depression]. AB - Intravenous clomipramine (n = 105) and oral clomipramine (n = 64) were compared in a control study of 169 inpatients with major depression. The therapeutic effects were evaluated with four-degree scale and the rating scales of HDS and CGI. The results showed intravenous group has earlier response and better antidepressive effects than oral group within treatment period of 2 weeks. No significant differences between two groups were found in anticholinergic side reaction. Clinical useful values of intravenous clomipramine were discussed. PMID- 1591964 TI - Cardiac evaluation. AB - Over the past decade there has been a dramatic, rapid development of new imaging modalities used in the evaluation of the cardiac patient. These newer techniques are frequently complex and specialized in their application and interpretation. Nonetheless, the prevalence of cardiac disease in the United States, and the wide application of these diagnostic tests, mandate that the well-rounded clinician has a basic understanding of the utility of these diagnostic modalities. Unfortunately, the burgeoning field of cardiac imaging seems at times to overshadow our most important basic diagnostic tools, namely, the history, physical exam, chest radiograph, and electrocardiogram (ECG). This review will attempt to impart a basic understanding of the newer cardiac diagnostic tests and their utility in various disease states. Emphasis on the importance of the basic clinical exam and the precise integration of specific diagnostic tests into the cardiac evaluation will be emphasized. The article will deliver a basic review of exercise treadmill testing, echocardiography, radionuclide imaging techniques, magnetic resonance imaging, and cardiac catheterization. It is hoped that this review will impart to the noncardiologist clinician a basic understanding of the cardiovascular diagnostic techniques so that an accurate, precise, cost effective, efficient diagnostic plan for the patient with cardiovascular disease can be developed and applied. PMID- 1591965 TI - Early receptor potentials recorded in humans via dermal electrodes. Normative data and prognostic value in retinal detachment. AB - Early receptor potentials were recorded by skin electrodes positioned at the inferior orbital margin in 32 patients with recent bullous retinal detachments and in nine patients with old, total retinal detachments. Results were compared to those obtained in a normative study performed on 200 healthy subjects. In patients with recent retinal detachments, no significant variations were found with respect to normal subjects. In patients with old retinal detachments, an early receptor potential of decreased amplitude was recorded in only five subjects, while in the other four the trace could not be separated from the noise. PMID- 1591966 TI - Comparison of the human electro-oculographic response to green and near ultraviolet stimuli. AB - We recorded the electro-oculogram from 27 normal subjects by means of green and near-ultraviolet (UVA) stimulation. After a 40-minute dark-adaptation period, baseline responses were recorded. In response to the green stimulus, the electro oculogram increased from this level by an average (+/- standard error of the mean) of 49.5% +/- 4.0%. Although the predicted scotopic effectiveness of the ultraviolet stimulus was more than 3 log units below that of the green stimulus, the near-ultraviolet-induced electro-oculogram increased to an average of 21.9% +/- 3.0% above baseline. This response cannot be due to lens fluorescence to the near-ultraviolet stimulus, since two aphakic subjects had electro-oculographic responses of 32% and 76% above baseline to near-ultraviolet stimuli. Neither the green nor the ultraviolet electro-oculogram changed significantly with age. These large responses to near-ultraviolet stimulation demonstrate the need for standardizing light sources for electro-oculographic testing because the degree of near-ultraviolet irradiance varies considerably according to their design characteristics. PMID- 1591967 TI - Relationships between the electroretinogram a-wave, b-wave and oscillatory potentials and their application to clinical diagnosis. AB - The electroretinogram is the electrical response of the retina to a light stimulus. The amplitude and temporal pattern of its components, the a-wave, the b wave and the oscillatory potentials, depend on the functional integrity of the retina, on the intensity of test flash reaching the retina and on the ambient illumination. The latter contributions to the normal variability in the electroretinogram can be circumvented by constructing the relationships between the different electroretinogram waves. The electroretinogram responses were recorded from 18 dark-adapted subjects with normal vision. The slope of the a wave and the amplitude of the b-waves were measured in the time domain. The oscillatory potentials were isolated by a digital filter and were transformed to the frequency domain for quantitative measurement. The relationship between each pair of variables could be fitted by linear segments. Our findings suggest that this mode of electroretinogram analysis can be useful in localizing the site of action of retinal disorders and that the relationship between the a-wave slope and the power density of the oscillatory potentials is a useful index for identifying disorders of the inner retina. PMID- 1591968 TI - Diurnal variations in the electroretinographic c-wave and retinal melatonin content in rats with inherited retinal dystrophy. AB - The inability of retinal pigment epithelium to phagocytose shed photoreceptor disks is a cause of retinal degeneration in the Royal College of Surgeons rat; retinal pigment epithelial phagocytosis and disk shedding are regulated by the diurnal rhythm of retinal melatonin level. The diurnal rhythms of the electroretinogram (particularly that of the retinal pigment epithelial potential, the electroretinographic c-wave) and retinal melatonin content were thus investigated in Royal College of Surgeons rats from postnatal day 17 to 24, the period preceding retinal degeneration. The amplitudes of both the b- and c-waves of the electroretinogram fell significantly during the peak time of rod disk shedding and rose after the time of expected light off in the control and dystrophic rats. While the b-wave rhythms did not differ between the two strains, diurnal changes in the c-wave were significantly less distinct in the dystrophic rats than in controls. This difference may reflect lack of phagocytosis in dystrophic rats. Furthermore, the ERG c-wave was significantly larger and prolonged, and the retinal melatonin content higher, in dystrophic rats of this age group than in controls. It appears that retinal melatonin metabolism may play an important role in the maintenance of retinal pigment epithelial and photoreceptor function. PMID- 1591969 TI - Steady-state visual evoked cortical potentials from stimulation of visual field quadrants. Optimizing pattern variables for the size of the field to be investigated. AB - The effects of check size and stimulus size were investigated to optimize the steady-state visual evoked cortical potentials from pattern-reversal stimulation of the visual field quadrants. Check sizes of 15', 30', 60', 90', 120' and 180' were investigated at a pattern reversal rate of 11.6 per second for field sizes varying from 2 degrees x 2 degrees to 24 degrees x 24 degrees. The visual evoked cortical potentials were recorded from mid occipital, right occipital and left occipital positions. In the inferonasal quadrant, the largest amplitudes were obtained with 30' and 60' check sizes; however, for these check sizes, the visual evoked cortical potential yielded limited additional information for field sizes greater than 4 degrees x 4 degrees and 6 degrees x 6 degrees, respectively. When a field size of 12 degrees x 12 degrees was investigated, a 90' check size was optimal. The results indicated that, with the above recording positions and check sizes of 15' to 120', there is an optimal number of pattern elements, 40 to 100, for stimulation of the inferonasal quadrant. This should be taken into account when a check size is selected to investigate a field quadrant of a particular size. Digital signal processing techniques were applied to analyze the visual evoked cortical potential, and the system shows promise for objective examination of the visual field. PMID- 1591970 TI - Detection duration thresholds and evoked potential measures of stereosensitivity. AB - Visual evoked potentials have been proposed by some researchers to be more useful than behavioral techniques to evaluate stereo performance in children and certain clinical populations. Stimulus duration detection thresholds, visual evoked potentials, and scalp electrical potential distribution maps to dynamic random dot stereograms were studied. A high degree of correspondence was found between visual evoked potential amplitudes and behaviorally determined detection thresholds. Upper field stimuli had higher detection thresholds and generated lower-amplitude visual evoked potential responses than did centrally presented stimuli. For the most eccentrically presented stimuli, lower detection thresholds were found for stimuli presented in the right visual field than the left visual field. This finding was consistent with the pattern of VEP responses to be lateralized, with higher-amplitude responses recorded over left-hemisphere sites. The study examined a proposal that the major negative component of the stereoscopic visual evoked potential originates in cortical area V1. The results failed to support the proposal and were consistent with the main negative component of the VEP being generated in V2, rather than V1. PMID- 1591971 TI - Comparative effects of luminance and scatter on the pattern visual evoked potential and eye-hand reaction time. AB - We investigated the effect of reduced luminance and increased scatter on the pattern visual evoked potential and eye-hand reaction time evoked to a check size of 0.5 degrees in 10 normal subjects. Data analysis indicated that a reduction in luminance as well as an increase in scatter caused a statistically significant increase in the peak time of the pattern visual evoked potential P100 wave. The reaction time, however, was not significantly affected by the initial 0.9-log unit attenuation of the stimulus luminance or the 0.3 scatter filter. Further attenuation of luminance or increase of scatter also yielded statistically significant increases. Our results suggest that the reaction time is less affected by a reduction in luminance or an increase in scatter of a 0.5 degrees stimulus than the pattern visual evoked potential is and therefore represents a more reliable test to assess visual function, especially in the presence of medial opacities, which are known to reduce luminance and produce scatter. PMID- 1591972 TI - The effect of spatial frequency and contrast on the latency in the visual evoked potential. AB - The latency in the visual evoked potential was measured at spatial frequencies of 2-12 c/deg in 10 subjects. The contrast levels of the sinuosoidal grating patterns were set at 1.5, 1.75, 2.0, 2.25, 2.5, 2.75 and 3.0 log units above each subject's contrast sensitivity threshold. Two factors were shown to influence the latency: suprathreshold contrast and, to a lesser extent, spatial frequency. The visual evoked potential latencies at contrast sensitivity threshold were extrapolated. These threshold latencies showed considerable variation with spatial frequency and between subjects. Therefore, the visual evoked potential latency cannot be considered a useful tool for estimating the contrast sensitivity function. PMID- 1591973 TI - Macular electroretinograms to flicker and pattern stimulation in lamellar macular holes. AB - Steady-state macular (9 degrees x 9 degrees) electroretinograms in response to either sinusoidal flicker (focal electroretinogram) or counterphased sinusoidal gratings (pattern electroretinogram) were recorded in 14 patients with inner lamellar macular holes, in 4 patients with full-thickness macular holes and in 14 age-matched controls. Fourier analysis of focal and pattern electroretinograms yielded three main components: a first and a second harmonic to flicker, and a second harmonic to pattern. Recent evidence indicates that the first harmonic to flicker is of receptoral origin, whereas the flicker and pattern second harmonics represent, at least in part, the activity of different generators in the inner retina. When compared to controls, patients with inner lamellar holes showed significant amplitude reduction and phase delay for both flicker and pattern second harmonics, but not for the flicker first harmonic. Patients with full thickness holes showed significant amplitude reduction also for the flicker first harmonic. These results indicate a prevalent functional involvement of the inner retina in lamellar macular holes, which can be clinically detected by evaluating focal and pattern electroretinogram second harmonics. PMID- 1591974 TI - [Changes in the reactivity of the vascular wall under the effect of ionizing radiation]. PMID- 1591975 TI - [Biosynthesis of prostaglandins catalyzed by enzymes from wood degrading basidiomycetes]. PMID- 1591976 TI - [The effect of galactose on absorption of free glucose and glucose, liberated during hydrolysis of maltose and trehalose in the small intestine]. PMID- 1591977 TI - Supersensitivity to naloxone following acute morphine pretreatment in humans: behavioral, hormonal and physiological effects. AB - The effects of naloxone (10 mg/70 kg) given 6 h following acute exposure to morphine (4, 8, 16 mg/70 kg) were assessed in 5 opiate-abusing volunteers who were not physically dependent upon entering the study. Naloxone increased cortisol plasma levels more following morphine than placebo pretreatment. Naloxone reversed the effects of morphine on pupil diameter and oral temperature and decreased skin temperature as a function of morphine pretreatment. Subjects' ability to detect the effects of naloxone, their scores on an opiate-withdrawal questionnaire, and their visual-analog ratings of 'bad effects', 'chills', 'confused' and 'restlessness' increased when naloxone followed pretreatment with 8 and 16 mg, but not 4 mg, of morphine. Performance on the Digit Symbol Substitution Test was not discernibly affected under any of the dose conditions. Overall, results from the present study provide further evidence in humans that the administration of naloxone shortly following acute morphine pretreatment increases naloxone sensitivity, produces signs and symptoms typical of opiate withdrawal and that these effects are dependent on the dose of morphine administered. PMID- 1591978 TI - Personality and religion among female drug misusers. AB - Fifty female drug misusers completed the Eysenck Personality Questionnaire and the Francis scale of attitude towards Christianity on entry to a Christian residential rehabilitation programme. The data confirm the deviant personality profile of drug misusers, who score high on psychoticism and neuroticism and low on extroversion and the lie scale, and demonstrate that the general findings relating religious attitudes to the Eysenckian dimensions of personality among normal populations also hold good among this deviant group, thereby confirming the generalisability of the conclusion that it is psychoticism, rather than neuroticism or extroversion, which is fundamental to religiosity. The practical relevance of these findings is discussed for rehabilitation programmes which include spiritual or religious components. PMID- 1591979 TI - Interactions between alcohol and nicotine on intracranial self-stimulation and locomotor activity in rats. AB - These studies were aimed at investigating interactions between alcohol and nicotine on operant behavior and on locomotor activity. Independent groups of rats with electrodes in the lateral hypothalamus were trained to lever press for intracranial self-stimulation (ICSS) on either a fixed-ratio 15 (FR 15), FR 30, fixed-interval 15-second (FI 15-s) or FI 30-s schedule of reinforcement. In the FI 15-s experiment, nicotine increased and alcohol decreased responding. This also happened in the FI 30-s experiment; however, when the two drugs were combined, an increase in lever pressing occurred which was greater than that produced by nicotine alone. Nicotine increased rates in the FR 15 schedule but, when combined with alcohol, did not reverse the decrease in rates produced by alcohol. In the FR 30 schedule, nicotine also increased response rates, but did not reverse the decrease produced by alcohol in this paradigm. A separate group of animals was tested in a locomotor activity apparatus following administration of nicotine, alcohol or their combination. Nicotine increased locomotor activity and alcohol depressed it. However, when 0.10 or 0.17 mg/kg nicotine was combined with 0.3 g/kg alcohol, an increase greater than that produced by nicotine alone occurred. We have found that alcohol and nicotine together can produce a potentiation of nicotine's stimulatory effects depending upon the dose and the requirements of the task. PMID- 1591980 TI - Mortality in patients with dependence on prescription drugs. AB - In 1974 we started a follow-up of patients with different psychoactive substance use disorders (PSUD) according to DSM-III; 2082 cases out of 2127 were analyzed; 1370 patients had taken legal drugs (i.e. prescription drugs and/or over-the counter drugs); 444 patients suffered from abuse or dependence of legal drugs alone; 678 combined legal drugs and ethanol, and 248 cases combined legal and illegal drugs, often together with ethanol. A group of 712 alcoholics were included for comparison. Mean time under observation was 6.5 +/- 5.4 years, and 269 patients died. Mortality and survival were calculated and compared with expected survival from the normal population of the former Federal Republic of Germany. Mortality in all subgroups of PSUD was increased, the standardized mortality ratio (SMR) for patients on legal drugs alone being 2.1. Patients with legal plus illegal drugs had a SMR as high as 20.7; those with legal drugs plus ethanol 3.4; and alcoholics 4.2. The increased mortality seemed to be constant over the years. Mortality decreased in patients with stable abstinence. There was no clear sex difference. Abuse had a better prognosis than dependence. An estimation of potential life lost by the different PSUDs was attempted. Patients on legal drugs died from suicides, malignancies or accidents (including intoxication). In alcoholics or patients on legal drugs plus ethanol malignoma, liver cirrhosis, accident and suicide were the most prominent causes of death. PMID- 1591981 TI - Chronic effects of marihuana smoking on luteinizing hormone, follicle-stimulating hormone and prolactin levels in human males. AB - The purpose of this investigation was to assess the chronic effects of marihuana smoking on the basal and stimulated secretion of the pituitary hormones luteinizing hormone (LH), follicle-stimulating (FSH) and prolactin (PRL). Ten male chronic marihuana users and 10 age- and sex-matched healthy volunteers were studied by measuring hormone levels before and after i.v. administration of thyrotropin releasing hormone (TRH) and gonadotropin releasing hormone (GnRH). The basal and stimulated levels of LH were reduced in marihuana users, whereas FSH and PRL levels and responses were not different from the control subjects. The chronic use of marihuana may selectively impair the hypothalamic control mechanisms regulating LH secretion. PMID- 1591983 TI - Acute ethanol effects on sensory/motor function in baboons with a history of chronic ethanol ingestion. AB - Baboons with a history of chronic, daily ethanol ingestion were subsequently studied under conditions that assessed the effects of acute oral self administration of ethanol on auditory and visual threshold functions and reaction times. During the post-chronic experiment reported herein, the animals consumed specific amounts of ethanol twice weekly (0.1, 0.32, 1.0 or 1.3 g/kg), following which they immediately performed psychophysical tests designed to assess ethanol's effects on sensory thresholds and reaction times. Clear, dose-related increases in reaction times were observed following ethanol doses greater than 0.32 g/kg. Trends within individual threshold functions were consistent with systematic changes in auditory and visual threshold sensitivities of 1-3 dB at the high ethanol doses. Reaction time increases ranged from 25 to 180 ms above baseline levels at the highest dose (a 15% average increase). These general findings however, were in contrast to data obtained in the same animals under conditions of daily, chronic ethanol administration which characteristically showed greater sensory/motor effects of up to twice the magnitude of those observed with single doses. PMID- 1591982 TI - Empirical subtypes of DSM-III-R alcohol dependence: United States, 1988. AB - The purpose of the present study was to quantify the degree of heterogeneity of the DSM-III-R alcohol dependence category by comparing the number of potential subtypes of dependence to those empirically observed in a general population survey. Forty-one percent (n = 189) of the 466 potential subtypes of DSM-III-R alcohol dependence were observed, indicating that the category is indeed heterogeneous, but not as heterogeneous as theoretically predicted. Variations in the number, percent and configuration of empirical subtypes of dependence are discussed in terms of coincident morbidity, premature death from alcoholism or death from other competing causes, reporting biases and differences in drinking patterns. The predominance of the 'tolerance' 'withdrawal' and 'impaired control over drinking' criteria among the empirically observed subtypes of dependence are examined within the context of the physiological dependence subtype proposed for the DSM-IV category of alcohol dependence and difficulties encountered in operationalizing these diagnostic criteria. The relevance of study findings to the validation of diagnostic categories in psychiatry is also highlighted. PMID- 1591984 TI - Choosing and using a pancreatic enzyme supplement. PMID- 1591985 TI - Preventing and treating deep vein thrombosis. PMID- 1591986 TI - Bulimia nervosa--common in women. PMID- 1591987 TI - Management of infantile colic. PMID- 1591988 TI - Calcipotriol ointment for plaque psoriasis. PMID- 1591989 TI - Metronidazole gel for smelly tumours. PMID- 1591990 TI - Amorolfine--putting a gloss on infected nails. PMID- 1591991 TI - Long acting diltiazem tablets. PMID- 1591992 TI - Is chewing gum good for teeth? PMID- 1591993 TI - Epoetin--an important advance. PMID- 1591994 TI - Embryonic stem cell-derived cystic embryoid bodies form vascular channels: an in vitro model of blood vessel development. AB - Murine embryonic stem cells can differentiate in vitro to form cystic embryoid bodies (CEB) that contain different structures and cell types. The blood islands are one such structure that consist of immature hematopoietic cells surrounded by endothelial cells, the first identifiable vascular cells. CEBs differentiated in vitro developed blood islands initially, and subsequently these blood islands matured to form vascular channels containing hematopoietic cells. Phase contrast microscopy demonstrated the presence of channels in mature CEBs grown in suspension culture, and high resolution light and electron microscopy showed that the cells lining these channels were endothelial cells. The channels appeared less organized than the vasculature of the mature yolk sac. The hematopoietic cells were occasionally seen 'flowing' through the CEB channels, although their numbers were reduced relative to the yolk sac. Analysis of primary CEB cultures showed the presence of cells with two characteristics of endothelial cells: approximately 30% of the cells labelled with fluorescent acetylated low density lipoprotein and a small number of cells were positive for von Willebrand's factor by immunostaining. Thus we conclude that a primitive vasculature forms in CEBs differentiated in vitro, and that not only primary differentiation of endothelial cells but also some aspects of vascular maturation are intrinsic to this cell culture system. CEBs are therefore a useful model for the study of developmental blood vessel formation. PMID- 1591995 TI - Distribution analysis of transferred donor cells in avian blastodermal chimeras. AB - Blastodermal chimeras were constructed by transferring quail cells to chick blastoderm. Contribution of donor cells to host were histologically analyzed utilizing an in situ cell marker. Of the embryos produced by injection of stage XI-XIII quail cells into stage XI-2 chick blastoderm, more than 50 percent were definite chimeras. The restriction on the spatial arrangement of donor cells was induced by varying the stage of host. Ectodermal chimerism was limited to the head region and no mesodermal chimerism was shown when the quail cells were injected into stage XI-XIII blastoderm. Mesodermal and ectodermal chimerisms were limited to the trunk, not to the head region, when the quail cells were injected into the stage XIV-2 blastoderm. In these chimeras, however, some of the injected quail cells formed ectopic epidermal cysts. Consequently, the stage XIV-2 blastoderm may become intolerant of the injected cells. Our results suggest that it is possible to obtain chimeras that have chimerism limited to a particular germ layer and region by varying the stage of donor cell injection. Injected quail cells contributed to endodermal tissues and primordial germ cells regardless of the injection site. The quail-chick blastodermal chimeras could be useful in the production of a transgenic chicken and in the investigation of immunological tolerance. PMID- 1591996 TI - Two myogenic lineages within the developing somite. AB - It is well known that the muscles of the vertebrate body are derived from the somite. Precursor cells within the somite proper form the back or axial muscles while other precursor cells migrate away from the somite to populate the muscle of the limbs and ventral body wall. Although both types of muscle are generally thought of as arising from a common progenitor population, the myotome, recent evidence points to developmental differences in these two groups of muscles which may reflect different developmental lineages. To test the lineage hypothesis, we used microsurgery and the chick-quail nucleolar marker system to follow the developmental fate of the lateral and medial halves of somites at the wing level. The results showed that the structures of the mature somite (myotome and sclerotome) are derived virtually exclusively from cells residing in the medial half of the newly formed somite. On the other hand, virtually all of the cells residing in the lateral half of the newly formed somite are destined to leave the somite proper and populate the limb muscle and, probably, other somite-derived mesenchymal structures in the limb and ventral body wall. Switch-graft experiments show that the two halves of newly formed somites are largely interchangeable demonstrating that their ultimate developmental fate is position dependent and that it becomes fixed as a result of extrinsic influences which act during later stages of somitogenesis. We conclude that at least two distinct myogenic lineages exist in the somite; one giving rise to the muscles of the back and the other giving rise to the limb musculature. PMID- 1591997 TI - Survival of photoreceptor neurons in the compound eye of Drosophila depends on connections with the optic ganglia. AB - The importance of retinal innervation for the normal development of the optic ganglia in Drosophila is well documented. However, little is known about retrograde effects of the optic lobe on the adult photoreceptor cells (R-cells). We addressed this question by examining the survival of R-cells in mutant flies where R-cells do not connect to the brain. Although imaginal R-cells develop normally in the absence of connections to the optic lobes, we find that their continued survival requires these connections. Genetic mosaic studies with the disconnected (disco) mutation demonstrate that survival of R-cells does not depend on the genotype of the eye, but is correlated with the presence of connections to the optic ganglia. These results suggest the existence of retrograde interactions in the Drosophila visual system reminiscent of trophic interactions found in vertebrates. PMID- 1591998 TI - The fate of medial edge epithelial cells during palatal fusion in vitro: an analysis by DiI labelling and confocal microscopy. AB - Fusion of bilateral shelves, to form the definitive mammalian secondary palate, is critically dependent on removal of the medial edge cells that constitute the midline epithelial seam. Conflicting views suggest that programmed apoptotic death or epithelial-mesenchymal transformation of these cells is predominantly involved. Due in part to the potentially ambiguous interpretation of static images and the notable absence of fate mapping studies, the process by which this is achieved has, however, remained mechanistically equivocal. Using an in vitro mouse model, we have selectively labelled palatal epithelia with DiI and examined the fate of medial edge epithelial (MEE) cells during palatal fusion by localisation using a combination of conventional histology and confocal laser scanning microscopy (CLSM). In dynamic studies using CLSM, we have made repetitive observations of the same palatal cultures in time-course investigations. Our results concurred with the established morphological criteria of seam degeneration; however, they provided no evidence of MEE cell death or transformation. Instead we report that MEE cells migrate nasally and orally out of the seam and are recruited into, and constitute, epithelial triangles on both the oral and nasal aspects of the palate. Subsequently these cells become incorporated into the oral and nasal epithelia on the surface of the palate. We hypothesize an alternative method of seam degeneration in vivo which largely conserves the MEE population by recruiting it into the nasal and oral epithelia. PMID- 1591999 TI - Communication compartments in hair follicles and their implication in differentiative control. AB - Observations on hair follicles presented in this paper show that boundaries to junctional communication are formed between groups of cells following different pathways of differentiation. The patterns of junctional communication in the bulbs of rat vibrissa follicles and human hair follicles were studied by microinjection of the fluorescent tracer dye Lucifer Yellow CH. Dye spread was extensive between undifferentiated cells of the hair bulb matrix but communication boundaries were found between groups of morphologically distinct cells. For example, boundaries to dye spread were observed between undifferentiated matrix cells and cells in the early stage of differentiation into the inner root sheath, between Huxley's and Henle's layers in the early inner root sheath and between cells of the cuticle and cortex of the hair. Dye did not spread between epithelial cells of the hair bulb and mesenchymal cells of the connective tissue sheath or dermal papilla. The patterns of dye spread became more complex (increased boundary formation and subcompartmentation) as differentiation progressed in higher regions of the hair bulb. The observed communication can be related to previous ultrastructural studies by others on the distribution of gap junctions in the wool follicle. These results show that junctional communication, with its consequent intercellular spread of small ions and molecules, is associated with uniformity of expression and behaviour within cell populations and that interruption of communication through the formation of boundaries and communication compartments is temporally and spatially related to the production of subpopulations of cells committed to the expression of different phenotypes. PMID- 1592000 TI - Characterisation of dystrophin during development of human skeletal muscle. AB - Dystrophin, the 427 x 10(3) Mr product of the Duchenne muscular dystrophy (DMD) gene, was studied in human foetal skeletal muscle from 9 to 26 weeks of gestation. Dystrophin could be detected from at least 9 weeks of gestation at the sarcolemmal membrane of most myotubes, though there was differential staining with antibodies raised to various regions of the protein. Dystrophin immunostaining increased and became more uniform with age and by 26 weeks of gestation there was intense sarcolemmal staining of all myotubes. On a Western blot, a doublet of smaller relative molecular mass than that seen in adult tissue was detected in all foetuses studied. There was a gradual increase in abundance of the upper band from 9 to 26 weeks, and the lower band, although present in low amounts in young foetuses, increased significantly between 20 and 26 weeks of gestation. These data indicate that there are several specific isoforms of dystrophin present in developing skeletal muscle, though the role of these is unknown. PMID- 1592001 TI - Posttranscriptional regulation of ectoderm-specific gene expression in early sea urchin embryos. AB - During development of the sea urchin Strongylocentrotus purpuratus embryo, transcription of the Spec1 and actin CyIIIa genes is activated and the corresponding mRNAs accumulate specifically in ectoderm cells. We show that in gastrulae this tissue specificity of mRNA accumulation is regulated largely if not entirely at a posttranscriptional level. We used RNAase protection assays with intron and exon probes to measure the levels of nuclear precursors and mature message, respectively, in total RNA from embryo fractions enriched for ectoderm (Ect) or endoderm+mesenchyme (E/M) cells. These measurements demonstrate that E/M cells, which do not accumulate Spec1 and actin CyIIIa mRNAs, contain high levels of intron transcripts, indicating that cells of the E/M tissues transcribe these genes. At later stages, transcripts containing intron sequences are restricted to ectoderm cells. These results indicate that there is a transition from posttranscriptional to transcriptional regulation of tissue specific mRNA accumulation during the gastrula stage. Measurements of transcription rate by nuclear run-on assays substantiate this conclusion for Spec1 and extend it to two other genes, SpEGFI and Spec2c, which also encode ectoderm-specific mRNAs. Posttranscriptional regulation was not observed for the SM50 gene whose mRNA accumulates only in primary mesenchyme cells, or for actin CyI which is expressed predominantly in E/M cells of gastrulae. PMID- 1592002 TI - Identification and characterization of Drosophila female germ line transcriptional control elements. AB - The highly organized structure of the Drosophila ovary makes it an ideal system for studying mechanisms of differential gene expression. Here we report the identification of a 171 bp sequence from the 5' end of the hsp26 gene that functions as a female germ-line-specific transcriptional regulator when linked in two copies to a basal promoter. The regulator is active only in nondividing cells of the germ line, i.e., only in nurse cells and oocytes. It is not active in any examined tissue or cell type outside of the female germ line. Copper nuclease footprinting studies show that the germ line regulator contains two binding sites for each of two different ovarian nuclear factors. Point mutations in the DNA target sites of either nuclear factor abolish in vitro binding and in vivo transcriptional activity, indicating that each factor is a positive activator of nurse cell/oocyte transcription. The two factors may represent different classes of activator proteins, since an increase in the copy number of one factor's DNA target site cannot compensate for a decrease in the copy number of the other factor's target site. PMID- 1592003 TI - Expression of vascular endothelial growth factor during embryonic angiogenesis and endothelial cell differentiation. AB - Vascular endothelial growth factor (VEGF) is a secreted angiogenic mitogen whose target cell specificity appears to be restricted to vascular endothelial cells. Such factors are likely candidates for regulatory molecules involved in endothelial growth control. We have characterized the murine VEGF gene and have analysed its expression pattern in embryogenesis, particularly during brain angiogenesis. Analysis of cDNA clones predicted the existence of three molecular forms of VEGF which differ in size due to heterogeneity at the carboxy terminus of the protein. The predicted mature proteins consist of 120, 164 or 188 amino acid residues. Homodimers of the two lower molecular weight forms, but not of the higher molecular weight form, were secreted by COS cells transfected with the corresponding cDNAs and were equally potent in stimulating the growth of endothelial cells. During brain development, VEGF transcript levels were abundant in the ventricular neuroectoderm of embryonic and postnatal brain when endothelial cells proliferate rapidly but were reduced in the adult when endothelial cell proliferation has ceased. The temporal and spatial expression of VEGF is consistent with the hypothesis that VEGF is synthesized and released by the ventricular neuroectoderm and may induce the ingrowth of capillaries from the perineural vascular plexus. In addition to the transient expression during brain development, a persistent expression of VEGF was observed in epithelial cells adjacent to fenestrated endothelium, e.g. in choroid plexus and in kidney glomeruli. The data are consistent with a role of VEGF as a multifunctional regulator of endothelial cell growth and differentiation. PMID- 1592004 TI - Risk factors associated with antepartum fetal death. AB - This study examined risk factors that contribute to antepartum fetal death. The population-based sample included 416 antepartum fetal deaths and 449 normal births as controls, from 29 hospitals in Shanghai, China. In addition to small for-gestational-age and severe pregnancy-induced hypertension, exposure to environmental hazards (radiation, chemicals and pesticides) was significantly associated with fetal death. Elevated relative risk of fetal death was also found in pregnant women whose husbands smoked (adjusted odds ratio = 1.4). Clinicopathologic evidence further confirmed that exposure to hazards, especially in the first trimester, increased the risks of congenital anomalies (odds ratio = 2.7) and antepartum fetal death from congenital malformations (odds ratio = 3.5). This study also showed that threatened abortion was a significant predictor of risk of fetal death. No significant relationships were identified between sex of fetus, mild or moderate pregnancy-induced hypertension, maternal anemia and antepartum fetal death. PMID- 1592005 TI - Developmental course of general movements in early infancy. I. Descriptive analysis of change in form. AB - In order to describe the developmental changes of general movements (GM) in early infancy and to relate them to changes in other aspects of the neurological repertoire, the spontaneous motility in supine position was recorded on video tape at 4-week intervals in a group of twenty-two full-term healthy infants aged 2-18 weeks. Each follow-up session included a neurological examination. In newborn infants GM have a 'writhing' quality. The movements are characterized by a tight appearance, a relatively slow speed and a limited amplitude. The 'writhing' character of the GM is gradually broken down into a so-called 'fidgety' quality. These GM are typified by an ongoing flow of small movements occurring irregularly all over the body. The transformation of GM from a 'writhing' character into a 'fidgety' character was related more closely to postmenstrual than to postnatal age. 'Fidgety' GM were almost constantly present at the age of 8-12 weeks. In the third month very rapid arm movements ('swipes' and 'swats') occurred. The developmental changes in the form of the GM and those of the neurological repertoire showed no significant correlation. This demonstrates that within the normal CNS the various functional modules develop autonomously. PMID- 1592006 TI - Immunoreactive arginine vasopressin in human fetal and neonatal skeletal muscle. AB - We provide evidence for the presence of arginine vasopressin (AVP) in human fetal and neonatal skeletal muscle using a combination of specific RIA, tangential flow ultrafiltration and reverse-phase HPLC separation. The IR-AVP concentrations are negatively correlated with gestational age (r = -0.75, P less than 0.0001) and range from 1 to 10 pmol/g wet wt at 15 weeks gestation to 0.04 pmol/g wet wt at term. This IR-AVP substance is of low molecular weight (less than 3000 mol. wt), elutes in the same position as standard AVP after HPLC separation and is detected by four different anti-AVP antisera. PMID- 1592007 TI - Monocytosis in preterm infants. AB - In sick preterm neonates receiving intensive care a spectacular rise in monocyte count has frequently been observed in sequential full blood examinations. The etiology of this has not previously been investigated and this study examines clinical factors that may contribute to this finding. Thirty (5.1%) of the 587 neonates who required intensive care during the study period had significant monocytosis (absolute count greater than 1700/mm3). Their mean gestation was 29 weeks (range 26-32 weeks). Monocytic response occurred at an age of 5.5 +/- 3 (mean +/- S.D.) days with 20% occurring at birth, 57% in the first week and 23% in the second week of life and lasted for 19.8 +/- 16 days (mean +/- S.D.). Most reached peak levels within two weeks and these ranged between 2,170 and 7176 per mm3. Analysis of the clinical variables against 37 controls revealed lower mean birth weight and gestational age, and higher incidence of leukocytosis, multiple transfusions, albumin infusions and theophylline therapy in the study group in comparison to the controls (P less than 0.001). No significant difference was found in maternal risk factors (pre-eclampsia, diabetes and amnionitis), birth asphyxia, respiratory disease, parenteral nutrition, proven infection and antibiotic therapy. An unexpected association with maternal steroid therapy was demonstrated. It is speculated that monocytosis represents a physiological though immature response of the marrow of small premature infants to a variety of exogenous stimuli including drugs and foreign protein infusions. PMID- 1592008 TI - Developmental course of general movements in early infancy. II. EMG correlates. AB - In order to study developmental changes in muscle co-ordination during the first postnatal months, simultaneous polymyographic recordings and video-recordings were made during spontaneous movements of 22 healthy infants, who were followed from birth onwards. During the first 2 months general movements (GM) change from movements with a so-called 'writhing' character, which have a tight appearance, a relatively slow speed and a limited amplitude, into GM with a 'fidgety' character, which consist of an ongoing flow of small, elegant movements. We hypothesized that this transformation would coincide with a change from a pattern of co-contraction of antagonistic muscle groups into a pattern of reciprocal activation. This was not the case, a pattern of co-activation of antagonistic muscle groups remained the prevailing pattern. With increasing age, we found shorter burst durations of phasic activity, an attenuation of burst amplitude and a decrease of tonic background activity. These changes were attributed to a reduction of the sensitivity of the motor units due to spinal and supraspinal reorganization. It is hypothesized that the so-called 'bistable' properties of motoneurones play a central role in the observed phenomena: in neonates motor units are apt at displaying sustained activity, at 2 months of age the threshold for reaching this maintained activity increases, resulting in a low level of excitation of motor units during spontaneous movements. In the third month rapid arm movements ('swipes' and 'swats') develop. The 'swats' are characterized by a consistent pattern of reciprocal activity of antagonistic (shoulder) muscles. PMID- 1592009 TI - The effects of obstetric conditions on neonatal behaviour in Japanese infants. AB - The effects of obstetric conditions on neonatal neurological status and neonatal behaviour were studied using a sample of 159 Japanese infants who were neurologically and obstetrically low-risk. Observations were made using Prechtl's neonatal neurological examination and Brazelton's neonatal behavioural assessment on the 5th day after birth. The main obstetric conditions which relate to neurological status and behaviour are anaesthesia, induction of labour, previous spontaneous abortion, previous induced abortion and maternal alcohol consumption. The main areas of neurological status and behaviour which are affected by obstetric conditions are lability of states, alertness, orientation, habituation, activity, hand to mouth activity, defensive movements, head control and resistance to cuddle. The results of the present study suggest that even a small difference of low-risk obstetric conditions is related to differences in neonatal neurological status and neonatal behaviour. On the one hand inter-item relations were found and on the other hand the results supported Prechtl's finding [16] that an analysis of the relation between obstetric conditions and neonatal status as a whole is preferable to an item by item comparison. PMID- 1592010 TI - A study on neonatal behaviour comparing between two groups from different cultural backgrounds. AB - Fifty-one British newborn infants and 51 Japanese newborn infants were compared using Prechtl's neonatal neurological examination and Brazelton's neonatal behavioural assessment scale on the 5th day after birth. Statistically significant differences were found between the two groups. British infants were more responsive to the stimuli displayed and showed better self-quieting activity and motor performance than Japanese infants and there were differences in the course of state change and of habituation; however, some responses may have been affected by daily posture. These results are partly supported by the findings of other studies. As conditions which have previously been reported to affect neonatal status were matched between the two groups, with cultural background being the only exception, it can be said that the differences arose from the cultural background. PMID- 1592011 TI - Case study. Erythropoietin for anaemia in a preterm Jehovah's Witness baby. AB - An infant born at 24 weeks gestation to Jehovah's Witness parents was made a Ward of Court and treated against their wishes with blood products. Erythropoietin was used without obvious benefit, but the child did well. The parents did not reject the child and maintained a good relationship with medical and nursing staff. We present this case in the light of current discussions on child welfare and recent reform of the law relating to child protection and highlight the many difficult dilemmas faced by the medical team. PMID- 1592012 TI - Water and electrolyte contents, cell pH, and membrane potential of primary cultures of astrocytes from DBA, C57, and SW mice. AB - Some basic properties of primary cultures of astrocytes derived from the cerebral cortex of an audiogenic seizure-sensitive strain of mice, DBA/2J (DBA), were studied with different approaches. The results were compared with those of audiogenic seizure-resistant strains, C57BL/6J (C57) and Swiss Webster (SW). Contents of intracellular water, protein, and DNA of DBA astrocytes were 0.673 +/ 0.019 ml/g cells, 0.082 +/- 0.006 g/g cells, and 0.0072 +/- 0.0005 g/g cells, respectively. These results are not different from those of either C57 or SW astrocytes. Intracellular concentration of K+, Na+, and Cl- ([K+]1, [Na+]1, and [Cl-]1) derived from the flame photometric and from the radioisotope uptake data of DBA astrocytes were 120.4 +/- 8.5, 25.9 +/- 3.2, and 26.8 +/- 1.8 mM/L cell H2O, respectively. [Na+]1 and [Cl-]1 in DBA astrocytes were lower than those in C57 and SW astrocytes. In DBA astrocytes, SITS decreased the cell/medium ratio (C/M) of 36Cl- and increased the C/M of 125I-; ouabain increased the C/M of 22Na+ and decreased the C/M of 125I-; bumetanide decreased the C/M of both 36Cl- and 22Na+; and NaClO4 decreased the C/M of 125I-. Similar results were observed in both C57 and SW astrocytes. Intracellular pH (pHi) as determined with 14C-DMO of astrocytes in HEPES-buffered saline solution averaged 7.04 +/- 0.03 for DBA, 7.01 +/- 0.02 for C57, and 6.97 +/- 0.02 for SW mice when pH of medium was maintained at 7.4. Modification of ion (HCO3-, Cl-, Na+, and K+) concentration and pH of culture medium all changed the pHi of astrocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592013 TI - Chronic/semichronic limbic epilepsy produced by microinjection of tetanus toxin in cat hippocampus. AB - We describe an animal preparation in which a semichronic or chronic limbic epileptiform syndrome can be produced reliably by unilateral microinjection of tetanus toxin in cat ventral hippocampus. Injections were given at 1-week intervals until abnormal EEG activity was observed. After two to five injections, the animals abruptly began to exhibit intermittent spikes and subclinical discharges that soon gave way to spontaneous and recurrent behavioral seizures which gradually increased in frequency, duration, and severity in the next 12-48 h. Anticonvulsant therapy (phenobarbital, PB) was required within the first 3 days of the syndrome, since life-threatening generalized tonic-clonic seizures (GTCS) and status epilepticus would develop if the animal were left untreated. If severe seizures were prevented by antiepileptic drugs (AEDs) there was complete remission of the syndrome and repeat injection was necessary to reinitiate seizures. Animals that experienced severe seizures or that were reinjected after remission developed a chronic seizure syndrome and could be maintained with AEDs for long times (greater than 1 year) without significant debilitation. Although early spikes and subclinical discharges were typically focal to ipsilateral limbic sites, initial seizures appeared explosively in the form of a high amplitude, high-frequency discharge, which often had an apparently bilateral limbic onset. On the other hand, chronic seizures had much more gradual onset and spread, often consisting of periodic sharp waves or low-amplitude sinusoidal discharge that was more clearly focal to ipsilateral limbic sites. Throughout the syndrome, ictal behavioral manifestations were highly stereotyped and very comparable to those described by other investigators in studies of clinical and experimental limbic epilepsy. All animals exhibited signs of independent contralateral involvement during the syndrome, ranging from independent contralateral spikes to subclinical discharges with a clear contralateral onset. None of the animals exhibited structural lesions on histologic examination at the level of light microscopy. PMID- 1592014 TI - Seizures induced by the cocaine metabolite benzoylecgonine in rats. AB - The half-life (t1/2) of cocaine is relatively short, but some of the consequences of its use, such as seizures and strokes, can occur hours after exposure. This led us to hypothesize that a metabolite of cocaine may be responsible for some of those delayed sequelae. We evaluated the potential of the major metabolite of cocaine, benzoylecgonine (BE), to cause seizures. Two separate equimolar doses (0.2 and 0.4 mumol) of either cocaine or BE were injected ventricularly in unanesthetized juvenile rats. Treated rats were then evaluated for incidence, latency, and seizure pattern or for locomotor activity in animals without seizures. BE-Induced seizures occurred more frequently and had significantly longer latencies than those induced by equimolar amounts of cocaine. Whereas cocaine-induced seizures were best characterized as brief, generalized, and tonic and resulted in death, those induced by BE were prolonged, often multiple and mixed in type, and rarely resulted in death. Electrical recordings from the hippocampus showed a rhythmic progression in EEG frequency and voltage with clinical seizure expression. BE-Injected rats that did not have seizures had significantly more locomotor activity than cocaine-injected animals without seizures. The finding that cocaine- and BE-induced seizures differ in several respects suggests more than one mechanism for cocaine-induced seizures and emphasizes the importance of a cocaine metabolite, BE. PMID- 1592015 TI - Changes in the strength of recurrent inhibition in cobalt-induced epilepsy. AB - Changes in the strength of recurrent inhibition in the feline cortex in cobalt (CoCl2)-induced epilepsy were observed. The strength of inhibition was analyzed in terms of paired-pulse depression of the amplitude of somatosensory evoked potentials (SEPs) elicited by stimulation of the ventral posterolateral (VPL) thalamic nucleus. An enhancement in recurrent inhibition was observed shortly after CoCl2 application. The size of the amplitude of cortical evoked potentials (EPs) elicited by VPL stimulation increased simultaneously. The reduction of inhibition that appeared later was associated with afterdischarges (ADs) evoked by VPL stimulation. These ADs frequently extended to epileptic discharges. These results suggest that the reduction in recurrent inhibition induced by CoCl2 application plays an important role in the spread of seizure activity. PMID- 1592016 TI - Clonidine prevents corticotropin releasing factor-induced epileptogenic activity in rats. AB - Studies have shown that intracerebroventricular (i.c.v.) injection (10-20 micrograms) of corticotropin releasing factor (CRF) in rats induces epileptiform activity characterized by a regular (pacemaker-like) spiking pattern located in hippocampal leads. CRF has also been shown to increase the firing rate of noradrenergic neurons in the locus ceruleus. Our experiments clarified the possible role of norepinephrine (NE) in mediating hippocampal activity of CRF. Intraperitoneal (i.p.) injection of the alpha 2-agonist clonidine at a dose of 0.5-5 micrograms/kg prevented, in a dose-related manner, the hippocampal epileptiform activity induced by CRF (20 micrograms i.c.v.). Our results suggest a possible role of NE in CRF-induced spiking activity. PMID- 1592017 TI - Age-dependent differences in the anticonvulsant effects of 2-amino-7-phosphono heptanoic acid or ketamine infusions into the substantia nigra of rats. AB - Infusions of 2-amino-7-phosphonoheptanoic acid (AP7) or ketamine into the substantia nigra pars reticulata (SNPR) of adult rats increase the latency of onset to seizures induced by the convulsant ether flurothyl. Nigral infusions of AP7 or ketamine in concentrations up to 10 times greater than the adult dose are ineffective in 16-day-old rats. These results suggest that differences in seizure susceptibility between adult and immature rats may be related to differences in excitatory amino acid neurotransmission in the SN. PMID- 1592018 TI - Prevalence of epilepsy in adults in northern Sweden. AB - A multisource medical register review identified persons with active epilepsy in northern Sweden. Seven hundred thirteen persons aged greater than or equal to 17 years with epilepsy were determined on the prevalence day, December 31, 1985. The overall prevalence was 553 in 100,000 (566 in 100,000 if adjusted to the 1980 U.S. population). The ratio of males to females was 1.1, with a male prevalence of 575 and a female prevalence of 530 in 100,000. Age-specific prevalences varied between 530-644 in 100,000 except in persons aged greater than or equal to 70 years, for whom the prevalence was 321 in 100,000. Partial seizures were most common, 333 in 100,000, of whom the majority (250 in 100,000) had seizures that occasionally were secondarily generalized. Mental retardation was the foremost coexistent disorder, noted in 23%. The mean yearly seizure frequency was higher in persons with mental retardation than in nonretarded persons. Seventeen percent had seizures during the last week, 57% during the last year, whereas 16% had greater than or equal to 5 years' freedom from seizures. Most had onset of epilepsy before age 20 years. A presumed etiology was noted in 35%, more often in men than in women. Cerebrovascular disease was the most commonly identified presumed cause. Other nonepileptic diseases/disabilities were noted in 47%. PMID- 1592019 TI - Public attitudes toward epilepsy in Denmark. AB - Social acceptance of persons with epilepsy very often constitutes a considerable problem for patients and their relatives. Nationwide opinion pools on the knowledge of and public attitude toward epilepsy have been taken in several countries, but never in Denmark. We report a Gallup survey of the general knowledge of and attitude toward epilepsy. A representative population of 1,500 persons aged greater than or equal to 15 years was selected in a four-state proportional sampling procedure. Ninety-seven percent of respondents had heard or read about epilepsy, 60% of these knew a person with epilepsy, and 50% had seen an epileptic seizure. The attitudes toward social acceptance and employment of persons with epilepsy were generally favorable, but 7% had objections to social contact between their children and persons with epilepsy in the playground and at school and 7% had objections to equal employment. Familiarity with persons with epilepsy was correlated to questions about attitudes and general knowledge of epilepsy. Such knowledge and public attitude in Denmark are mainly positive, but we believe that a continuous information campaign about epilepsy is essential, especially among youth. PMID- 1592020 TI - The natural history of untreated epilepsy in a rural community in Africa. AB - The duration of epilepsy was evaluated in over 460 previously untreated patients who attended newly established epilepsy clinics in a rural area of Malawi. The mean duration at first attendance was 6.5 years. It was found that as the duration of active epilepsy increased, the number of patients having epilepsy of a given duration decreased. Possible explanations for this result, such as an increasing incidence of epilepsy or a high mortality rate, are considered, but thought to be unlikely. Since the distribution of patients with epilepsy of differing durations is similar to that described in a study carried out in Tonbridge, Kent, England, where the number of patients in remission was found to increase over time, it is postulated that the observed distribution also reflects remission, and that spontaneous remission of epilepsy is a frequent occurrence, independent of antiepileptic drug treatment. PMID- 1592021 TI - Epilepsy, driving laws, and patient disclosure to physicians. AB - To avoid loss of driving privileges, patients with epilepsy may elect not to report seizures to their physician or to the Department of Motor Vehicles (DMV). Reporting to the physician may differ depending upon the type of law in effect, i.e., mandatory physician reporting versus patient reporting to the DMV. Nondisclosure to the physician may have important consequences with regard to seizure management. We surveyed patients at two adult seizure clinics to determine the effect of driving laws on patients' reporting to their physician. One hundred fifty-eight patients completed an anonymous questionnaire asking whether they would report a breakthrough seizure under a physician versus a patient DMV reporting system. Under patient reporting, 96% would inform their physician and 56% would report to the DMV. Under physician reporting, 84% would inform their physician. This falls to 72% when considering currently driving patients only. An additional 9-17% of patients would continue to drive with a suspended license. In all, 53% would remain driving under patient reporting and 33% under physician reporting; however, with physician reporting, half of the illegally driving patients would have compromised their medical care, potentially increasing driving risk. PMID- 1592022 TI - Epilepsy in ancient India. AB - The ancient Indian medical system, Ayurveda, meaning science of life, is the oldest system of medicine in the world. Epilepsy is defined as Apasmara: apa, meaning negation or loss of; smara, meaning recollection or consciousness. Aura was recognized and was called Apasmara Poorva Roopa. A large number of symptoms indicative of aura were listed. Worthy of mention are subjective sensation of sounds, sensation of darkness, feeling of delusion, and dream-like state. An actual attack of Apasmara includes falling down; shaking of the hands, legs, and body; rolling up of the eyes; grinding of the teeth; and foaming at the mouth. Four major types of epilepsy based on the disturbance of doshas (humors) that govern the physiological and physiochemical activities of the body are mentioned. Apasmara is considered a dangerous disease that is chronic and difficult to treat. Several causes are mentioned. Treatment included correcting the etiological factors and dietary regimen and avoiding dangerous places that may result in injuries. PMID- 1592023 TI - Occipital lobe seizures related to clinically asymptomatic celiac disease in adulthood. AB - We report the electroclinical ictal findings of four epileptic patients with clinically asymptomatic celiac disease (CD). Celiac disease diagnosis was suspected by past history and/or computed tomography (CT) findings in all patients and confirmed by laboratory tests and jejunal biopsy. All patients had paroxysmal visual manifestations and ictal EEG discharges arising from the occipital lobe. Epilepsy evolution was favorable in two patients and severe in 2, regardless of CT evidence of occipital corticosubcortical calcifications in 2 patients. Occipital lobe seizures may be characteristic of the epilepsy related to CD, and epileptic patients with these seizures of unknown etiology should be carefully investigated for malabsorption. If past history and/or laboratory tests suggest gastrointestinal (GI) dysfunction they should also undergo small intestinal biopsy even if they do not have GI tract symptoms. PMID- 1592024 TI - EEG and seizures in children with hemolytic-uremic syndrome. AB - The EEG results of 11 children, ages 1-15 years, who presented with hemolytic uremic syndrome complicated by seizures 3-10 days after the prodrome were studied. In four children who experienced generalized tonic-clonic seizures, the EEGs demonstrated diffuse delta slowing with no focality. All recovered without neurological deficit or a residual seizure disorder. Of seven children who experienced partial seizures, six had structural lesions on cranial computed tomography and residual focal neurological deficits with epilepsy. The EEGs in two patients revealed focal spikes and slowing consistent with the lateralization of the partial seizures, in four it was characterized by atypical "burst suppression," and in one showed epochs of high-amplitude delta slowing alternating with generalized suppression. Although episodic and generalized burst suppression is usually regarded as a grave prognostic indicator, all four subjects recovered. PMID- 1592025 TI - Epilepsy in schizencephaly: abnormal cortical organization studied by somatosensory evoked potentials. AB - Median nerve short-latency somatosensory evoked potentials (MN-SSEP) are recorded from the scalp to assess parietal lobe function and from the cortex to identify primary sensory and motor areas before epilepsy surgery. Nevertheless, the origins of many of the MN-SSEP waveforms and the reliability of this technique for localizing the central sulcus are not definitively known. We studied a child with a unilateral, closed, right parietal schizencephalic cleft and frequent simple partial seizures before the child underwent cortical resection. The sensory examination, neuroimaging, and electrical brain stimulation findings indicated a normal thalamus and an abnormal parietal lobe. Scalp-recorded MN SSEPs showed intact widespread N18 potentials bilaterally, but absent right, although normal left parietal N20 and P27 waveforms. Cortically recorded MN-SSEPs could not localize the central sulcus owing to an absence of the expected negative potential over the right postcentral gyrus and the presence of waves with abnormal latencies over the precentral cortex. These findings suggest that: (a) the N18 potential probably originates at or below the level of the thalamus, (b) the N20 and P27 peaks are most likely generated by parietal cortex or white matter, and (c) cortically recorded MN-SSEPs can fail to localize the central sulcus before epilepsy surgery when congenital anomalies exist in the parietal lobe. PMID- 1592027 TI - Unilateral opercular macrogyria and benign childhood epilepsy with centrotemporal (rolandic) spikes: report of a case. AB - An 18-year-old mentally normal epileptic boy had frequent left brachiofacial or unilateral motor seizures which started at age 4 years and ceased 10 years later. Seizures were exclusively sleep-related. No relapse followed antiepileptic drug (AED) discontinuation. Left arm slight paresis and left hand astereognosia occurred at age 10 years. Awake EEGs showed persistent right rolandic discharges increased by sleep. Somatosensory evoked potentials (SEPs) were giant with left median nerve stimulation. Computed tomography (CT) and magnetic resonance imaging (MRI) disclosed right opercular macrogyria. We suggest that the structural brain lesion was causally related to his "idiopathic" partial epilepsy. Similar case reports and pathologic studies will elucidate the morphologic substrate of the underlying functional disorder in idiopathic partial epilepsies. PMID- 1592026 TI - Epilepsy after stroke. AB - A retrospective follow-up of 200 consecutive stroke patients [ischemic brain infarction (IBI) 157, intracerebral hemorrhage (ICH) 20, subarachnoid hemorrhage (SAH) 23] who were in need of ambulatory rehabilitation was conducted for a mean period of 40 months after stroke. Epilepsy developed in 33 (17%) patients. The occurrence of epilepsy was 14% in IBI, 15% in ICH, and 35% in SAH. Significantly more patients developed epilepsy in the SAH group than in the IBI group (8 of 23 vs. 22 of 157, p less than 0.05). Of the 33 patients, 15% had their first seizures within the first 2 weeks after stroke, and 55% developed epilepsy in 6 months. Forty-eight percent of the patients had generalized seizures. Antiepileptic drug (AED) treatment was started in 28 of 33 patients, of whom 17 still had seizures during follow-up. Epilepsy was an important consequence of stroke among patients who needed rehabilitation, especially in SAH patients. In most, this was due to arterial spasm leading to IBI. PMID- 1592028 TI - Lack of pathologic changes in human temporal lobes after transcranial magnetic stimulation. AB - Most animal studies have failed to demonstrate pathologic changes in the brain after transcranial magnetic stimulation (TMS). Nevertheless, vacuolar lesions in the cortex of rats after TMS have been reported. We report the first histopathologic studies of human brains after TMS in 2 patients with epilepsy who underwent temporal lobectomies. They had been involved in a study to determine the speech-dominant hemisphere by TMS and had received approximately 2,000 stimuli centered over the resected temporal lobe. Histologic study of the surgical specimens did not show any lesions attributable to TMS in these 2 patients. PMID- 1592029 TI - Compulsive somatosensory self-stimulation inducing epileptic seizures. AB - Three children who had been diagnosed as having infantile spasms with major psychomotor retardation were referred for the persistence of series of spasm-like seizures, which were resistant to antiepileptic drug treatment, beyond infancy. Serial seizures were elicited by a compulsive self-stimulating behavior that was documented by long-term video-polygraphy. These behaviors implicated proprioceptive inputs: tapping on the chin in one case, flexion and external rotation of the leg with dislocation of the femur in one case, a particular posturing of the body followed by rhythmic shaking of the head in the last case. This clinical picture seems to constitute a particular type of outcome for infantile spasms and is particularly resistant to therapy. PMID- 1592030 TI - Usefulness of blue sunglasses in photosensitive epilepsy. AB - The suppressive effect of sunglasses upon photoparoxysmal responses (PPRs) elicited by 15-Hz flicker stimuli with a low luminance of nearly 10 nits was studied in eight patients with photosensitive epilepsy. Using three commercially available sunglasses of neutral density (ND), blue, and brown, the influence upon generalized PPRs elicited by a flickering dot pattern (FDP) and red flicker (RF) stimuli was separately examined in six patients; the luminance of the visual stimuli decreased from roughly one-fifth (ND and brown sunglasses) to one-tenth (blue sunglasses). With FDP stimulation, four of the six patients wearing each of the three sunglasses had no provocation of PPRs, whereas two of the six patients had provocation of generalized PPRs with all of the sunglasses. With RF stimulation, two of the six patients wearing ND sunglasses had provocation of generalized PPRs; three of the six patients wearing brown sunglasses had similar provocation; in contrast, none of the six patients showed provocation of PPRs while wearing blue sunglasses. These results suggest that the suppressive effect of the three sunglasses on FDP stimulation is mainly due to a luminance diminution, whereas that of blue sunglasses on RF stimulation is produced by an inhibitory effect of short wavelengths and possibly by a luminance diminution. Thus, blue sunglasses are thought to be useful in the treatment of patients with photosensitive epilepsy. PMID- 1592031 TI - Rotatory seizures. AB - We report seven cases of "rotatory seizures" with patients rotating around their axis one or several times. Contralateral EEG foci were localized in frontal and temporal regions. Computed tomography scan of three patients showed no structural lesion. PMID- 1592032 TI - Somatosensory evoked potentials in juvenile myoclonic epilepsy. AB - We analyzed the somatosensory evoked potentials (SEP) of 35 patients with juvenile myoclonic epilepsy (JME), 26 patients with idiopathic generalized epilepsy (IGE), and a control group consisting of 24 healthy people. The N19-P25 interval was significantly prolonged in the IGE group both as compared with the JME and control groups. This finding may be related to antiepileptic drug (AED) treatment, principally phenytoin (PHT). No differences were noted in N19 amplitude in any group. The P25 and N33 amplitudes were significantly higher in the JME group. In 5 patients of the JME group (14%) "giant SEP" were observed, but no differences were evident in the electroclinical characteristics with respect to the other JME patients. JME is one of the causes of giant-SEP. PMID- 1592033 TI - Spike morphology in childhood focal epilepsy: relationship to syndromic classification. AB - The waveform morphology of interictal spike activity associated with uncontrolled childhood focal epilepsy was quantified in 40 patients by a computer-based technique. The findings were then analyzed with respect to epileptic syndromes. Samples of spike activity from each patient were characterized by determination of average amplitude (A), duration (D), and sharpness (S). A single morphologic index, the composite spike parameter (CSP), was also derived from the basic spike parameters (CSP = A x D/S). The spikes of patients in the benign focal epilepsy category differed from those of patients in other syndromic categories (symptomatic, cryptogenic, and Landau-Kleffner). Specifically, they were higher in amplitude, longer in duration, less sharp, and had a higher CSP value. The pretreatment spike parameters did not differ significantly in patients who responded favorably to initial antiepileptic drug (AED) therapy as compared with those whose seizures were harder to control. The findings suggest that quantitative assessment of interictal spike morphology may help develop a more objective basis for classifying patients according to epileptic syndrome. PMID- 1592034 TI - Morphological patterns of seizures recorded intracranially. AB - We analyzed the frequency and morphological characteristics of the initial EEG manifestations of spontaneous seizures recorded from depth and subdural electrodes in 26 patients for whom pathological analysis of the area of seizure onset was available after resective surgery. Pathological features considered to be positive findings included well-defined structural lesions (hamartoma, neoplasm) or strictly defined mesial temporal sclerosis. Seizure onset was characterized by the frequency of the rhythmic discharge greater than 2 Hz in the first second and by the presence or absence of periodic low-frequency spikes (less than 2 Hz) preceding this stable change in background frequency. These features were correlated with the presence or absence of pathologic abnormalities in temporal and extratemporal locations. Although all patterns and frequencies of seizure onset were recorded in both medial temporal and extratemporal locations, medial temporal seizure onset was significantly more likely to have high frequency (greater than 13 Hz, p less than 0.00001) and tended to show periodic spikes prior to the seizure when it was associated with medial temporal sclerosis compared to when it was not. Extratemporal seizure onset associated with abnormal pathological substrate was significantly more likely to have a lower frequency (less than 13 Hz, p less than 0.05) and no periodic spikes before seizure onset (p less than 0.00001) than extratemporal seizure onset recorded from areas without pathological findings. Variability of seizure onset frequency was a characteristic of temporal, but not extratemporal, seizures (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592035 TI - Neurosurgical treatment of refractory status epilepticus. AB - Refractory status epilepticus (RSE) is defined as status epilepticus that continues despite aggressive treatment. A 9.8-year-old boy with a past history of daily left focal motor seizures was transferred to University of California at Los Angeles (UCLA) Hospital in pentobarbital coma after 4 days in RSE. The RSE was treated with very high doses of all appropriate antiepileptic drugs (AEDs), alone and in combination. The pentobarbital was titrated to burst suppression on EEG, but whenever pentobarbital was decreased, the seizures recurred. An ictal positron tomography scan of glucose metabolism demonstrated a right frontal area of hypermetabolism corresponding to an epileptic focus on EEG and magnetic resonance lesion. Eight days after the boy was admitted to UCLA, the right frontal focus was surgically removed, with immediate control of the status epilepticus. Whereas before onset of RSE, he had daily focal seizures, the boy has been seizure-free postoperatively for greater than 1 year. Operative treatment should be considered in patients with RSE in whom a focus of seizure onset can be demonstrated and who are reasonably considered surgical candidates. PMID- 1592036 TI - Serum copper and zinc levels in epileptic children with valproate treatment. AB - Valproate (VPA) induces zinc (Zn) deficiency in experimental animals, but whether VPA treatment induces deterioration of serum trace metal homeostasis in humans is uncertain. We measured serum copper (Cu) and Zn levels in epileptic children treated with VPA and/or other antiepileptic drugs (AEDs). Patients treated with VPA monotherapy had significantly lower levels of serum Cu (82.2 +/- 16.6 micrograms/dl) than normal controls (97.3 +/- 23.0 micrograms/dl). Patients treated with VPA in addition to some other AED also had significantly lower levels of serum Cu (84.8 +/- 20.0 micrograms/dl). Serum Cu concentrations in patients treated with AEDs except for VPA (87.7 +/- 19.1 micrograms/dl) were not statistically different from those of control subjects. In contrast to the reported results of animal experiments, serum Zn levels were not altered in patients with VPA treatment. Although none of our patients showed any symptoms of Cu deficiency, we should pay attention to potential Cu deficiency in patients with VPA treatment. PMID- 1592037 TI - Comparison of AccuLevel and TDx: evaluation of on-site monitoring of antiepileptic drugs. AB - Therapeutic drug monitoring, an important aid in antiepileptic drug (AED) therapy, has a lag time before results are obtained from clinical laboratories. The AccuLevel test is an enzyme immunochromatographic method for quantitative measurement of AEDs including phenobarbital (PB), phenytoin (PHT), and carbamazepine (CBZ), with results available within 20 min. A comparison between AccuLevel and TDx, (fluorescence polarization immunoassay) was conducted in 233 paired blood samples from patients with AED therapy, including 12 Eskimo children receiving treatment in Greenland. Forty-five blood samples were analyzed for PB, 80 for PHT, and 108 for CBZ. Linear regression analysis showed good agreement between the two methods (r = 0.951, 0.958, and 0.945, respectively). The test is easy to perform, but care must be taken to follow the correct procedure, or inaccuracies will result. That happened in some of our results. A reduction in lag time, using on-site drug monitoring, was demonstrated. The AccuLevel is a rapid, accurate, and convenient method for use in AED monitoring. PMID- 1592038 TI - A neuropharmacological evaluation of felbamate as a novel anticonvulsant. AB - Felbamate (2-phenyl-1,3-propanediol dicarbamate, FBM) was subjected to a series of carefully selected in vivo and in vitro tests to provide additional insight into mechanism of action, margin of safety, and clinical potential. FBM was effective against intracerebroventricular (i.c.v.) N-methyl-D-aspartate (NMDA) induced clonus and i.c.v. NMDA- and quisqualic acid (quis)-induced forelimb tonic extension in mice and ineffective against i.c.v. quis-induced clonus in mice. FBM was also effective in preventing the expression of Stage 5 kindled seizures in corneal-kindled rats. The calculated protective indices (rotorod median toxic dose divided by anticonvulsant median effective dose) ranged from 28 to 146 for those tests in which FBM displayed activity. With the in vitro tests, FBM did not significantly displace [3H]MK-801 from its binding site. In contrast, FBM was effective in blocking sustained repetitive firing in mouse spinal cord neurons grown in tissue culture (median inhibitory concentration 67 micrograms/ml). This effect on repetitive firing suggests indirectly that FBM modulates sodium channel conductance. The results, when compared to similar data for phenytoin, carbamazepine, valproate, and ethosuximide, support the concept that FBM is a relatively nontoxic agent with a unique profile of anticonvulsant action, a broad margin of safety, and a clinical potential that includes at least generalized tonic-clonic and complex partial seizures. PMID- 1592039 TI - Low fluorescence background electroblotting membrane for DNA sequencing. AB - A low fluorescence background polypropylene (PP) membrane has been developed for ultimate use as an electroblotting membrane in DNA sequencing based on fluorescence detection. The DNA binding capacity of this membrane is improved by a surface modification using radio frequency plasma discharge (RFPD) in ammonia gas. The RFPD operational parameters are evaluated both in terms of membrane nitrogen content and in terms of the product's capacity for binding radioisotope labeled DNA fragments. The surface morphologies of the derivatized membranes are examined by scanning electron microscopy; their mechanical and electrical properties, which are important for the subsequent sequencing procedures, are likewise established. Due to the goal of developing a membrane suitable for multiplex processing, in which the electroblotted DNA must withstand dozens of hybridization/stripping cycles, special attention is given the covalent attachment of DNA to the membrane. The modified PP membrane is evaluated in a multiplex sequencing application using radioisotope-labeled DNA probes, and found to yield somewhat better binding of a given amount of electroblotted DNA than the commonly used GeneScreen membrane. A tenfold repetition of the probing indicates little loss of signal; the membrane-bound DNA is stable upon storage and shows no detectable loss in probing efficiency after one month. PMID- 1592040 TI - Oligonucleotide fingerprinting of plant and fungal genomes: a comparison of radioactive, colorigenic and chemiluminescent detection methods. AB - Digoxigenated oligonucleotide probes complementary to simple repetitive DNA sequences were introduced into nonradioactive fingerprint analysis of plant and fungal DNA. The fragment patterns, obtained by blot hybridization of TaqI restricted DNA from chickpea (Cicer arietinum) and its fungal pathogen Ascochyta rabiei with digoxigenated probes and either a colorigenic or a chemiluminescent detection method, were compared to those obtained with 32P-labeled probes. In combination with alkaline phosphatase and its chemiluminescent substrate 3-(2' spiroadamantane)-4-methoxy-4-(3"-phosphoryloxy)phenyl- 1,2-dioxetane (AMPPD) digoxigenated oligonucleotides yielded clear-cut fingerprints with high signal-to background ratios within several minutes of exposure to X-ray films. The chemiluminescence reaction remained stable for at least two weeks. A comparison of banding patterns obtained by radioactive versus digoxigenin-based hybridization and detection techniques revealed substantial differences in the relative signal intensities of bands. Both nonradioactive techniques show a tendency to "equalize" band intensity differences. Whereas 32P-labeled oligonucleotides are also applicable to in situ hybridization with DNA immobilized in dried agarose gels, gel hybridization did not work efficiently with digoxigenated probes and either substrate. PMID- 1592041 TI - Impact of separation capacity on the isotachophoretic analysis of organic acids in human seminal plasma and prostatic fluid. AB - In the present study, the impact of pH of both the leading electrolyte and the sample on the separation capacity of an isotachophoretic system, used for the analysis of organic acids in human seminal plasma and prostatic fluid, was assessed. Generally, maximum separable amounts of eleven equimolar pairs of anions decreased within a pH range of 2.90-4.25 of the leading electrolyte due to increasing net mobilities of the analytes with rising pH. The values obtained under equimolar conditions were also valid for nonequimolar mixtures as long as the buffer capacity of the leading electrolyte was sufficient to maintain constant mobilities of the ionic species to be separated throughout the capillary. However, when the sample injected has a buffer capacity of its own and a pH higher than that of the leading electrolyte, separation capacity will vary. For that reason, the maximum separable amount of an aqueous solution of phosphate and citrate was higher than that obtained for seminal plasma. Hence, the injection volume had to be reduced in order to ensure complete resolution. Besides phosphate and citrate, which was the prime component of prostatic fluid, lactate, aspartate and glutamate could be quantitatively determined in seminal plasma with a precision of +/- 1.5%. PMID- 1592042 TI - The relative importance of transport phenomena in recycling isoelectric focusing. AB - The various transport phenomena involved in recycling isoelectric focusing are analyzed for their contributions to band spreading so as to find ways of improving the resolution of this liquid-phase protein purification method. A numerical model is proposed that takes into account diffusion, electroosmosis and electrophoretic migration as a function of pH. The electrohydrodynamic effects have so far been neglected in these calculations. The results of these calculations are compared with experimental measurements performed in different chamber geometries, with a variety of proteins and under different operating conditions, always chosen to avoid flow instabilities. This comparison shows that the resolution of this process is greatly impaired if the electroosmotic slip velocity at the wall is not suppressed. PMID- 1592043 TI - Cell electrophoretic characterization of abnormally expanded lymphocytes in autoimmune lprcg, lpr, gld and Yaa mice, and of thymocyte subsets. AB - Autoimmune mice carrying the lprcg/lprcg(lprcg),lpr/lpr(lpr),gld/gld(gld) and Yaa genes exhibit massive lymphoproliferation and a systemic lupus erythematosus-like syndrome. The surface markers of abnormally expanded lymphocytes used were Thy 1+, CD4-CD8- (double negative, DN) and CD45+ for lprcg, lpr, gld and (lprcg X gld) hybrid (F1-lprcg-gld) mice, and Ig+ for Yaa mice. To characterize the cell surface properties and differentiation pathway of lymphocytes in autoimmune mice, the cell electrophoretic mobility (EPM) was determined for the lymph node (LN), spleen and thymus cells. The EPM of lymphocytes derived from swollen LN was of the T cell type in lprcg, lpr, gld and F1-lprcg-gld mice, but of the B cell type in Yaa mice, indicating that the EPM of abnormally proliferated lymphocytes in autoimmune mice reflects their origin, and that the surface properties detected as a net negative charge were the same in abnormal and normal lymphocytes. The electrophoretic behavior of whole thymocytes was also the same in autoimmune and normal mice. The DN, and CD4+CD8- and CD4-CD8+ (single positive, SP) thymocytes from normal mice exhibited high EPM, while CD4+CD8+ (double positive, DP) thymocytes exhibited low EPM. According to the recent concept of intrathymic T cell differentiation (Schwartz, R. H., Cell. 1989, 57, 1073-1081), it is suggested that EPM of thymocytes may change with maturation in the following manner: DN thymocytes with high EPM----DP thymocytes with low EPM----SP thymocytes and autoimmune DN T cells with high EPM. PMID- 1592044 TI - S-carboxymethylation of proteins transferred onto polyvinylidene difluoride membranes followed by in situ protease digestion and amino acid microsequencing. AB - S-Carboxymethylation of immobilized proteins, separated by gel electrophoresis and transblotted to polyvinylidene difluoride (PVDF) membranes is described. In situ protease digestion was used to produce peptide fragments in high yields that were suitable for microsequencing. These fragments could also be used to produce peptide maps, obtained by reverse-phase high performance liquid chromatography (HPLC), that exhibited excellent reproducibility and were comparable to results obtained from digestions in solution. This technique makes it possible to identify Cys residues during Edman degradation. Approximately 70% of the amino acid residues from a protein were determined using only 50-200 pmol. Sufficient information for production of oligonucleotide probes was obtained using 10-50 pmol of material applied to a polyacrylamide gel. PMID- 1592045 TI - Five new alleles of plasma Zn-alpha 2-glycoprotein variants phenotyped by isoelectric focusing and immunoblotting in twelve populations. AB - Human Zn-alpha 2-glycoprotein (ZAG) in plasma samples from twelve populations was tested by immunoblotting after polyacrylamide gel isoelectric focusing. Eleven ZAG phenotypes produced by one common and nine rare alleles, including five new ones (ZAG*6-ZAG*10), were detected. Additionally, an application of separator IEF with N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) was found to be useful for discriminating the rare ZAG 7 band. PMID- 1592046 TI - Detection of oligoclonal IgG bands in cerebrospinal fluid by immunofixation after isoelectric focusing on polyacrylamide gels with the PhastSystem. AB - This paper describes the detection of oligoclonal bands of IgG immunoglobulins in cerebrospinal fluids (CSF) using isoelectric focusing (IEF) and immunofixation with the PhastSystem equipment. The proteins were separated by IEF on polyacrylamide gels, pH 3-9. The IgG immunoglobulins were then fixed by overlaying the gel with antihuman IgG antiserum. Fixed immunoglobulins were detected with silver staining in the PhastSystem Development Unit. One microliter of serum or CSF containing 15 mg/L of IgG was found to be optimal. The procedure had good reproducibility both with regard to IEF and silver staining of the fixed immunoglobulins. The manpower need was reduced, and the procedure has been found to be useful in the clinical laboratory. PMID- 1592047 TI - Use of principal components analysis for mutation detection with two-dimensional electrophoresis protein separations. AB - The application of two-dimensional electrophoresis (2-DE) to mutation detection requires the capability to monitor each protein in a 2-DE pattern for significant changes in abundance indicative of a mutation event. Previously, mutation searches were done using a univariate outlier detection method in which each protein spot was considered independently in a classical outlier search. An alternative approach to analysis of 2-DE patterns for quantitative changes is a multivariate procedure which takes advantage of the observation that protein spots in a 2-DE pattern often represent correlated rather than independent measurements. We have compared the efficiency of univariate and multivariate procedures for mutation detection using data from the Argonne National Laboratory 2-DE database of mouse liver proteins. Analyses involving a total of over 1500 gels were performed to compare the performance of a multivariate method based on principal components analysis (PCA) with the univariate method. Up to 279 spots from each pattern were used for PCA. First, a simulation was performed to assess the detection efficiency of PCA for single protein spots decreased in abundance by 50%. Then, the ability to detect actual mutations was tested using eight confirmed mutations. Results show that, compared to a univariate approach to analysis of data from the mouse model system, the multivariate method increases the number of protein spots on each 2-DE pattern that can be monitored for quantitative changes indicative of mutations by compensating for variables that contribute to the background quantitative variability of protein spots. PMID- 1592048 TI - Tissue-specific variation of pea mitochondrial polypeptides detected by computerized image analysis of two-dimensional electrophoresis gels. AB - A tissue-specific variation of a total of 152 mitochondria-associated polypeptides is detailed for etiolated leaves, epicotyls and roots from the pea, Pisum satisum L., using computerized image analysis. These organ systems possess, respectively, 128, 100, and 96 mitochondria-associated polypeptides with 38, 8, and 10, respectively, being unique to each. Seventy-one polypeptides were observed to be present in all gels, but some of these also underwent a variety of quantifiable changes. Two polypeptides were identified that varied similarly to a polypeptide of interest (W), known to be abundant in pea epicotyls and potato tubers. It is postulated that these latter three polypeptides are therefore probably related functionally. PMID- 1592049 TI - A rapid polymerase chain reaction method for identifying fixed specimens. AB - DNA profiling analysis of preserved tissue samples was achieved by using an extraction method which incorporated the use of a chelating resin "Chelex" to chelate inhibitory polyvalent metal ions. An automated sequencer was used to estimate sizes of low molecular weight trimeric and tetrameric microsatellites labelled with fluorescent dyes. The entire analysis can be completed within 48h. Probabilities of chance association using two microsatellites were calculated as ranging between 10(-2) and 10(-4). The methods described have considerable potential for use in routine genetic analysis of preserved samples. PMID- 1592050 TI - Resolution of circular, nicked circular and linear DNA, 4.4 kb in length, by electrophoresis in polyacrylamide solutions. AB - Circular DNA of more than 1,400 bp in size is known not to migrate into polyacrylamide gels. The migration of supercoiled plasmid pBR322 DNA (4,363 by) into uncrosslinked polyacrylamide (Mw 5 x 10(6)) solutions and its separation, on the basis of conformation, from its nicked form is demonstrated in this study. Migration of the supercoiled, nicked circular and linear forms of the plasmid DNA is retarded in proportion to the concentration of uncrosslinked polyacrylamide, the degree of retardation being highest for the nicked circular form. Decreasing the level of supercoiling of the covalently closed circular form by decreasing the concentration of the intercalating dye (ethidium homodimer) shows that the degree of retardation decreases in proportion to the superhelix density. PMID- 1592051 TI - Behaviour of triceps surae muscle-tendon complex in different jump conditions. AB - The force-length relationship of the human muscle-tendon complex (MTC) of the triceps surae and the achilles tendon was investigated in various stretch load conditions. Six male subjects performed various vertical jumps with maximal effort: squat jumps (SJ), counter movement jumps (CMJ) and drop jumps (DJ) from a height of 24 cm, 40 cm and 56 cm. The force-length relationship was calculated from the signals of the components of the ground reaction forces and the kinematic data obtained from the high-speed film records. Surface electromyograms (EMG) of the soleus, gastrocnemius and tibialis anterior muscles were also recorded. The force-length diagrams showed individually high sensitivity to the imposed stretch load. In conditions with relatively low stretch load requirements there was a counter-clockwise direction observable, indicating that the energy absorbed during the eccentric, or lengthening phase was lower than the energy delivered during the concentric, or shortening phase. In high load conditions this relationship was reversed indicating a negative energy balance. The EMG length diagrams of SJ and CMJ consisted of an initial isometric loading of the muscle, followed by a shortening phase with only slightly reduced EMG amplitudes. In DJ, however, the diagrams showed an initial lengthening of the MTC with fairly constant activation amplitudes. After 40 ms an isometric loading of the muscle, lasting for approximately 80 ms, was followed by a shortening phase. It was concluded that segmental stretch reflex activation represented the predominant activation process during the isometric loading phase, to meet the adequate stiffness properties of the MTC. PMID- 1592052 TI - Supramaximal cycle tests do not detect seasonal progression in performance in groups of elite speed skaters. AB - Seven female and eight male elite junior skaters performed cycle ergometer tests at four different times during the 1987/1988 season. The tests consisted of a Wingate-type 30-s sprint test and a 2.5-min supramaximal test. The subjects were tested in February, May and September 1987 and in January 1988. Maximal oxygen consumption was measured during the 2.5-min test. With the exception of the maximal oxygen consumption of the women in May which was about 6% lower than in the other three tests, no seasonal changes in the test results could be observed- this, in spite of a distinct increase in training volume (from 10 to more than 20 h.week-1) and training intensity in the course of the season. When the test data were compared to those of elite senior skaters, it appeared that the junior skaters showed the same values for mean power output during the sprint test [14.2 (SD 0.4) W.kg-1 for the men and 12.6 (SD 0.5) W.kg-1 for the women] and maximal oxygen consumption [63.1 (SD 2.8) ml.kg-1.min-1 for the men and 55.3 (SD 3.5) ml.kg-1.min-1 for the women, respectively] as found for senior skaters. It seemed, therefore, that the effects of training in these skaters had already levelled off in the period before they participated in this investigation. In contrast to previous studies, no relationship could be shown between the test results and skating performance. This was most likely due to the homogenous character of the groups (mean standard deviations in power and oxygen consumption were only 5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592053 TI - Reduced exercise hyperaemia in claf muscles working at high contraction frequencies. AB - The effects of muscle contraction frequency on blood flow to the calf muscle (Qcalf) were studied in six female subjects, who performed dynamic plantar flexions at frequencies of 20, 40, 60, 80 and 100 contractions.min-1, in a supine position. The Qcalf measured by a mercury-in-rubber strain gauge plethysmograph, increased as contraction frequency increased and reached a peak at 60-80 contractions.min-1. After 100 plantar flexions at 60 contractions.min-1, the mean Qcalf was 30.95 (SEM 4.52) ml.100 ml-1.min-1. At 100 contractions.min-1, however, it decreased significantly compared with that at 60 contractions.min-1 at a specified time (2 min or exhaustion) or after a fixed amount of work (100 contractions). The contraction frequency at which Qcalf reached a peak depended on the duration of exercise. The heart rate showed its highest mean value at 60 contractions.min-1 and decreased significantly at 100 contractions.min-1. The mean blood pressure was lower at 100 contractions.min-1 than at 60 contractions.min-1. The relaxation period between contractions, measured by recording the electromyogram from the gastrocnemius muscles, shortened markedly as the frequency increased; the mean value at 100 contractions.min-1 was 0.14 (SEM 0.02) s, which corresponded to 35.7% of the contraction time. This shortened relaxation period between contractions should have led to the inhibition of exercise hyperaemia at the higher contraction frequencies. PMID- 1592054 TI - Treadmill validation of an over-ground walking test to predict peak oxygen consumption. AB - The purpose of this study was to determine whether a test developed to predict maximal oxygen consumption (VO2max) during over-ground walking, was similarly valid as a predictor of peak oxygen consumption (VO2) when administered during a 1-mile (1.61 km) treadmill walk. Treadmill walk time, mean heart rate over the last 2 full min of the walk test, age, and body mass were entered into both generalized (GEN Eq.) and gender-specific (GSP Eq.) prediction equations. Overall results indicated a highly significant linear relationship between observed peak VO2 and GEN Eq. predicted values (r = 0.91), a total error (TE) of 5.26 ml.kg 1.min-1 and no significant difference between observed and predicted peak VO2 mean values. The peak VO2 for women (n = 75) was predicted accurately by GSP Eq. (r = 0.85; TE = 4.5 ml.kg-1.min-1), but was slightly overpredicted by GEN Eq. (overall mean difference = 1.4 ml.kg-1.min-1; r = 0.86; TE = 4.56 ml.kg-1.min-1). No significant differences between observed peak VO2 and either GEN Eq. (r = 0.85; TE = 4.3 ml.kg-1.min-1) or GSP Eq. (r = 0.85; TE = 4.8 ml.kg-1.min-1) predicted values were noted for men (n = 48) with peak VO2 values less than or equal to 55 ml.kg-1.min-1. However, both equations significantly underpredicted peak VO2 for the remaining high peak VO2 men (n = 22). In conclusion, the over ground walking test, when administered on a treadmill, is a valid method of predicting peak VO2 but underpredicts peak VO2 of subjects with observed high peak VO2 values. PMID- 1592055 TI - Comparison of mathematically determined blood lactate and heart rate "threshold" points and relationship with performance. AB - The purpose of this study was to investigate the relationship between threshold points for heart rate (Thfc) and blood lactate (Thla) as determined by two objective mathematical models. The models used were the mono-segmental exponential (EXP) model of Hughson et al. and the log-log (LOG) model of Beaver et al. Inter-correlations of these threshold points and correlations with performance were also studied. Seventeen elite runners (mean, SD = 27.5, 6.5 years; 1.73, 0.05 m; 63.8, 7.3 kg; and maximum oxygen consumption of 67.8, 3.7 ml.kg-1.min-1) performed two maximal multistage running field tests on a 183.9-m indoor track with inclined turns. The initial speed of 9 km.h-1 (2.5 m.s-1) was increased by 0.5 km.h-1 (0.14 m.s-1) every lap for the fc test and by 1 km.h-1 (0.28 m.s-1) every 4 min for the la test. After fitting the la or the fc data to the two mathematical models, the threshold speed was assessed in the LOG model from the intersection of the two linear segments (LOG-la; LOG-fc) and in the EXP model from a tangent point (TI-la; TI-fc). Thla and Thfc speeds computed with the two models were significantly different (P less than 0.001) and poorly correlated (LOG-la vs LOG-fc: r = 0.36, TI-la vs TI-fc: r = 0.13). In general, Thfc were less well correlated with performance than Thla. With two different objective mathematical models, this study has shown significant differences and poor correlations between Thla and Thfc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592056 TI - Changes in blood cell response following strenuous physical exercise. AB - The generation of tumour necrosis factor (TNF) and tissue factor activity in lipopolysaccharide (LPS) stimulated blood were studied in 25 healthy subjects before and after physical exercise of different intensities. Of the subjects a group of 9 were athletes who trained once to twice every day of the week, a second group of 8 exercised 3-7 times a week, and a third group of 8 exercised 4 5 times a month. The production of TNF in freshly drawn LPS stimulated blood in heparin, drawn from top athletes at rest was significantly lower than in the other subjects. The LPS induced concentrations of TNF-alpha of 2.73 (SEM 1.05) ng.ml-1 in the blood of the top athletes compared to 5.08 (SEM 0.7) ng.ml-1 and 7.6 (SEM 1.6) ng.ml-1, respectively, in the other two groups. The group that trained the least had the highest values. Immediately after exercise, the monocytes appeared to be less responsive to LPS stimulation, as a reduction of 47%-48% was observed in the top athletes and in the other group of well-trained individuals. The group that trained the least, which was also subjected to the least stressful exercise, had a 33% reduction in TNF production. Within 6 h the TNF concentration was back to pre-exercise values. Within 6 h the TNF concentration was back to pre-exercise values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592058 TI - Oxidation of exogenous carbohydrate during prolonged exercise: the effects of the carbohydrate type and its concentration. AB - We studied rates of exogenous carbohydrate (CHO) oxidation during 90 min of cycling exercise in trained cyclists exercising at 70% of maximal oxygen consumption (VO2max) when they ingested glucose, sucrose, or glucose polymer solutions at concentrations of 7.5%, 10% or 15%. Drinks were labelled with [U 14C]glucose or sucrose and were ingested at a rate of 100 ml.10 min-1. Rates of oxidation of the ingested CHO were calculated from the specific radio-activity of the labelled CHO, expired 14CO2 and carbon dioxide output (VCO2). Total CHO oxidation, determined from oxygen consumption and VCO2 was not influenced by CHO type or concentration. Gastric emptying (P = 0.01) and the rate of exogenous CHO oxidation (P = 0.028) was greatest for the glucose polymer solutions, and least for glucose. Although gastric emptying (P = 0.006) decreased with increasing CHO concentration, CHO delivery to the intestine and exogenous CHO oxidation increased linearly with increasing CHO concentration. The percentage of the CHO delivered to the intestine that was oxidized ranged from 30.0% for 7.5% CHO to 38.1% for 15% CHO. Our results indicated that the rate of gastric emptying for CHO was not controlled to provide a constant rate of energy delivery as is commonly believed and that factors subsequent to gastric emptying limit the rate of exogenous CHO oxidation from the ingested solution. PMID- 1592057 TI - Stimulation of the phagocytic function in guinea pig peritoneal macrophages by physical activity stress. AB - A study was made of all the different stages of the phagocytic function in peritoneal macrophages from male guinea pigs [3 (SD 1) months old] before, immediately after, and 24 h after being subjected to stress from physical activity (swimming until exhaustion). The early (10 min) and late (40 min) adherence to tissue substrates, chemotaxis, attachment and phagocytosis of Candida albicans, ingestion of inert particles (latex beads), and basal oxidative metabolism [measured by nitroblue tetrazolium (NBT) reduction] were significantly stimulated by the physical activity. After 24 h, late adherence, attachment capacities, and basal oxidative metabolism returned to basal values, whereas early adherence, chemotaxis, phagocytosis of cells and inert particles, and microbicidal capacity (production of superoxide anion measured by NBT reduction in presence of ingested material) remained significantly increased. The stress produced by physical activity, reflected in increased serum corticosterone values, led to a global stimulation of the phagocytic function. PMID- 1592059 TI - Biological responses to overload training in endurance sports. AB - Five subjects undertook 10 days of twice daily interval training sessions on a treadmill followed by 5 days of active recovery. On days 1, 6, 11, and 16 the subjects were required to undertake a test of submaximal and maximal work capacity on a treadmill combined with a performance test consisting of a run to exhaustion with the treadmill set at 18 km.h-1 and 1% gradient. Also on these days a pre-exercise blood sample was collected and analysed for a range of haematological, biochemical and immunological parameters. The subjects experienced a significant fall in performance on day 11 which had returned to pretraining levels on day 16. Serum ferritin concentrations were depressed significantly from pretraining concentrations at the conclusion of the recovery period while the expression of lymphocyte activation antigens (CD25+ and HLA-DR+) was increased both after the training phase and the recovery phase. The number of CD56+ cells in the peripheral circulation was depressed at the conclusion of the recovery period. Several parameters previously reported to change in association with overload training failing to reflect the decrease in performance experienced by subjects in this study, suggesting that overtraining may best be diagnosed through a multifactorial approach to the recognition of symptoms. The most important factor to consider may be a decrease in the level of performance following a regeneration period. The magnitude of this decreased performance necessary for the diagnosis of overtraining and the nature of an "appropriate" regeneration period are, however, difficult to define and may vary depending upon the training background of the subjects and the nature of the preceding training. It may or may not be associated with biochemical, haematological, physiological and immunological indicators. Individual cases may present a different range of symptoms and diagnosis of overtraining should not be excluded based on the failure of blood parameters to demonstrate variation. However, blood parameters may be useful to identify possible aetiology in each separate case report of over training. An outstanding factor to emerge from this study was the difficulty associated with an objective diagnosis of overtraining and this is a possible reason why there have been new accounts of overtraining research in the literature. PMID- 1592060 TI - Adipocyte responses to adrenaline and insulin in active and former sportsmen. AB - The rates of lipolysis and lipogenesis in adipocytes, isolated from biopsy samples of subcutaneous fat, was assessed by estimation of glycerol release during a 30-min incubation, and of the incorporation of 14C-glucose into lipids during a 1-h incubation at 37 degrees C, respectively. The subjects were six highly-qualified, active endurance sportsmen, eight former endurance sportsmen of international class, and six untrained young men. In the active sportsmen the basal rate of lipolysis was about half of that in the previously-active sportsmen and the untrained subjects, but after the addition of adrenaline (10(-4) or 5 x 10(-4) mol.l-1) the lipolysis rate was the highest. No differences were observed in the lipolytic rates in the former sportsmen compared to the untrained subjects. Gases of a comparatively high level of lipogenesis were found in the trained subjects. The addition of insulin (9 microU.ml-1) to isolated adipocytes caused a significant augmentation of individual rates of lipogenesis in the active sportsmen and the untrained persons but not in the previously-active sportsmen. In comparison with the active sportsmen, the previously active sportsmen revealed an increased basal rate of lipolysis and a reduced sensitivity to the lipogenic action of insulin. These findings suggest that these changes may have had significance in avoiding an increase of adipose tissue after a decrease in energy expenditure due to a change in physical activity. PMID- 1592061 TI - Exercise-induced muscle damage: effects of light exercise on damaged muscle. AB - The effects of performing light eccentric exercise (LB) during the period of recovery from a heavy eccentric exercise bout (HB) were studied. An experimental and a control group, each consisting of nine college age volunteers (seven women, two men) performed two HB--HB1 and HB2--14 days apart, using the elbow flexor and extensor muscles of one arm. The experimental group performed an additional LB on the day following the first HB. HB1 resulted in muscle soreness, muscle weakness, changes in elbow joint flexibility, and large delayed increases in serum creatine kinase (CK) activity. The HB2 produced smaller changes in all parameters, indicating that adaptation to the effects of eccentric exercise had occurred in the muscle. The LB did not alter muscle soreness, strength or elbow flexibility, but did reduce or delay CK activity increase after HB1. The LB had no apparent effect on adaptation to HB2. PMID- 1592062 TI - Changes in blood glutathione concentrations, and in erythrocyte glutathione reductase and glutathione S-transferase activity after running training and after participation in contests. AB - Previously sedentary men (n = 23) and women (n = 18) were trained to run a half marathon contest after 40 weeks. Total blood glutathione had increased by 20 weeks of training and had returned to normal after 40 weeks. Erythrocyte glutathione reductase activity had increased by 20 weeks and remained elevated after 40 weeks. This effect was accompanied by decreases in glutathione reductase coefficients, which indicated that increases in the presence of riboflavin may have been responsible for the changes in reductase activity. Erythrocyte glutathione S-transferase activity had increased slightly after 20 weeks of training and a much more marked increase was found after 40 weeks. This may have been indicative of the occurrence of lipid peroxidation in this phase of training. The participants ran a 15-km race after the first 20 weeks of training and a half marathon after 40 weeks. Blood glutathione tended to decrease after the 15-km race and increased after the half marathon. In both cases it had returned to normal values 5 days after the race. Erythrocyte glutathione reductase was elevated 1 day after the races, and had returned to normal after 5 days. This could also have been explained from concurrent changes in the riboflavin content of the erythrocytes. Erythrocyte glutathione S-transferase activity decreased after both races, but was restored 5 days after the half marathon while such was not the case after the 15-km race. PMID- 1592063 TI - Modification of myo-electric power spectrum in fatigue from 15% maximal voluntary contraction of human elbow flexor muscles, to limit of endurance: reflection of conduction velocity variation and/or centrally mediated mechanisms? AB - Isometric flexion of the right elbow at 15% of the maximal voluntary contraction (MVC) was maintained to the limit of endurance (elbow angle 135 degrees). The surface electromyogram (EMG) of the brachioradialis (BR) and biceps brachii (BB) muscles was recorded for calculation of conduction velocity (CV) by the cross correlation method, and determination of median frequency (fm) and root mean square (rms) amplitude. Perceived exertion was rated for both muscles, and heart rate and blood pressure were measured. The EMG of ten brief 15% MVC contractions distributed over a 30-min recovery period was also recorded. Eleven males in their twenties volunteered for the investigation. The average endurance time was 906 (SD 419) s. Mean CV for the unfatigued muscles was 4.2 (SD 0.41) m.s-1 (BR), and 4.3 (SD 0.29) m.s-1 (BB). The contraction caused a significant decrease in CV of BR (12%, P less than 0.001) whereas CV variation of BB remained insignificant. Concurrently the mean fm of both muscles dropped to approximately 66% of their initial values and their average rms amplitudes grew by approximately 380% (BR and BB: P less than 0.001, both parameters). The 1st min of recovery lowered the rms amplitudes by approximately 60% (BR and BB: P less than 0.01), while the fm increased to approximately 88% of the initial recording (BR, P less than 0.01; BB, P less than 0.05). The accompanying small increases in CV were beyond the level of significance. Over the next 29 min a significant parallel restitution in fm and CV took place; changes in fm evidenced a simple one to one reflection of relative CV variation. A similar uncomplicated linear causality between relative changes in CV and fm was hypothesized for the endurance contraction. Consequently, the 12% CV decrease of the BR accounted for only one-third of the fatigue induced fm reduction of 33%, while two-thirds were assumed to be attributable to centrally mediated regulatory interventions in motor unit (MU) performance. Independent of contributions from the virtually unchanged CV, the fm of the BB muscle decreased by 35%; from one subject exhibiting a remarkably manifest burst-type pattern of MU activity it is argued that synchronization/grouping of MU firing predominantly determined the power redistribution in the BB spectrum. PMID- 1592064 TI - Met-enkephalin, beta-endorphin and cortisol responses to sub-maximal exercise after sleep disturbances. AB - The present study compared the effects of partial sleep deprivation and the effects of an intake of a hypnotic compound (zolpidem) prior to bedtime, on sleep and on hormonal and metabolic adaptations to subsequent exercise. Sleep deprivation consisted of a delayed bedtime and an early getting-up time. Eight young subjects, who slept well and were highly trained athletes, were enrolled in this study. Sleep was recorded polygraphically and the following afternoon exercise was performed on a cycle ergometer for 30 min at 75% of maximal oxygen consumption (VO2max) after a 10-min warm up. Met-enkephalin, beta-endorphin, cortisol, and lactate concentrations were measured at rest and during exercise. The data obtained after experimental sleep, with and without medication were compared with those obtained in the reference condition with normal sleep. Both types of sleep reduction decreased the total sleep time, stage 2 sleep, and rapid eye movement sleep, whereas zolpidem administration did not modify either the duration of sleep or the sleep stages. After the reference night, plasma met enkephalin did not show any significant change at the end of the submaximal exercise, whereas beta-endorphin, cortisol, and lactic acid concentrations increased significantly in all subjects. The changes in concentration in beta endorphin were significantly related to the changes in cortisol (r = 0.78; P less than 0.01) and to the changes in plasma lactic acid (r = 0.58; P less than 0.05). Cortisol concentrations were also related to lactic acid values (r = 0.94; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592065 TI - Benefits of caffeine ingestion on sprint performance in trained and untrained swimmers. AB - The influence of specific training on benefits from caffeine (Caf) ingestion was examined during a sprint test in a group of highly trained swimmers (T) and compared with the response of a group of untrained occasional swimmers (UT). Seven T and seven UT subjects swam freestyle two randomly assigned 2 x 100 m distances, at maximal speed and separated by 20 min of passive recovery, once after Caf (250 mg) and once after placebo (Pla) ingestion. Anaerobic capacity was assessed by the mean velocity (meters per second) during each 100 m and blood was sampled from the fingertip just before and 1, 3, 5, 7, and 9 min after each 100 m for resting and maximal blood lactate concentration ([la-]b,max) determination. The [la-]bmax was significantly enhanced by Caf in both T and UT subjects (P less than 0.01). However, only T subjects exhibited significant improvement in their swimming velocity (P less than 0.01) after Caf or any significant impairment during the second 100 m. In light of these results, it appears that specific training is necessary to benefit from the metabolic adaptations induced by Caf during supramaximal exercise requiring a high anaerobic capacity. PMID- 1592066 TI - Hormonal adaptations and modelled responses in elite weightlifters during 6 weeks of training. AB - The concentrations of serum testosterone, sex-hormone-binding-globulin (SHBG) and luteinizing hormone (LH) were examined throughout 1-year of training in six elite weightlifters. A systems model, providing an estimation of fatigue and fitness, was applied to records of training volume and performance levels in clean and jerk. The analysis focused on a 6-week training period during which blood samples were taken at 2-week intervals. A 4-week period of intensive training (period I) could be distinguished from the following 2-week period of reduced training (period II). During period I, decreases in serum testosterone (P less than 0.05) and increases in serum LH concentrations (P less than 0.01) were observed; a significant correlation (r = 0.90, P less than 0.05) was also observed between the changes in serum LH concentration and in estimated fitness. The magnitude of LH response was not related to the change in serum androgens. On the other hand, the change in testosterone:SHBG ratio during period II was significantly correlated (r = 0.97, P less than 0.01) to the LH variations during period I. These finding suggested that the LH response indicated that the decrease in testosterone concentration was not primarily due to a dysfunction of the hypothalamic-pituitary system control, and that the fatigue/fitness status of an athlete could have influenced the LH response to the decreased testosterone concentration. The negative effect of training on hormonal balance could have been amplified by its influence on the hypothalamic-pituitary axis. A decrease in physiological stress would thus have been necessary for the completion of the effect of LH release on androgenic activity. PMID- 1592067 TI - Spinal cord sarcoidosis: MRI findings in response to treatment. AB - The unusual case of a 64-year-old female with sarcoidosis involving the spinal cord is reported. Diffuse swelling of the cord with nodular lesions was observed on MRI. The lesions showed a low intensity area on the T1-weighted image. Following the administration of gadolinium-diethylenetriamine pentaacetic acid, the spinal cord, especially the nodular lesions, was diffusely enhanced. Serum levels of anti-endothelial cell antibodies and antinuclear antibodies were elevated. The diagnosis was confirmed by transbronchial lung biopsy which revealed noncaseating granulomas with giant epithelioid cells. The administration of prednisolone, 40 mg/day for 4 weeks, induced a remission. PMID- 1592068 TI - Myoedema. A clinical and electrophysiological evaluation. AB - Stationary muscle mounding after muscle percussion without electrical muscle activity is called myoedema. Out of 105 patients with different neurological diseases, 88% had this phenomenon. Muscle conduction velocity and stimulated single fiber EMG disclosed no abnormalities. Myoedema is a normal physiological phenomenon, and its presence does not indicate a neuromuscular disorder. PMID- 1592069 TI - Autonomic dysfunction in men with Parkinson's disease. AB - Forty-eight men with Parkinson's disease (PD) were interviewed utilizing a questionnaire which evaluated autonomic function. The study population included PD patients (mean age: 65.8 years, mean duration of PD: 8 years) and 32 elderly healthy nonparkinsonian males (mean age: 70.4 years). We found a significantly higher prevalence of the following symptoms of autonomic dysfunction in the parkinsonian patients: erectile dysfunction (60.4 vs. 37.5%), sensation of incomplete bladder emptying (41.6 vs. 15.6%), urgency (45.8 vs. 3.125%), constipation (43.9 vs. 6.25%), dysphagia (22.9 vs. 6.25%) and orthostatic dizziness (21.95 vs. 0%). Eighty-nine percent of parkinsonian patients had at least one of these autonomic symptoms, compared to 43% of control subjects (p less than 0.05). This study is the first comprehensive survey of autonomic symptomatology in PD compared to elderly healthy controls and confirms that autonomic nervous system dysfunction is a pervasive problem in PD. Erectile dysfunction is a significant problem in this patient group and contributes to deterioration in the quality of life. PMID- 1592070 TI - Prognosis after therapy discontinuation in children with epilepsy. AB - Anticonvulsant therapy was stopped in 191 epileptic children (109 males and 82 females) after a seizure-free period of at least 2 years, independent of EEG findings, followed up for a minimum of 2 years after withdrawal. Overall, 43 (22.5%) had recurrence of seizures; of these, 79% relapsed within the 1st year after drug stopping and 93% within the 2nd year. The probability of remaining seizure free was 97% at the end of the withdrawal period, 82% 1 year later, 79% at 2 years and 77% at 5 years. In order to evaluate the risk of recurrence and the predictive factors of relapse, several parameters were investigated by univariate and multivariate statistical analysis. At univariate analysis, the factors which proved to be significantly correlated to relapses were: age at onset over 4 years, seizure-free time less than 2 years, sudden drug discontinuation, pathological EEG records during seizure-free time and paroxysmal responses to intermittent photic stimulation (IPS). At multivariate analysis, only age at onset, seizure-free time and sudden discontinuation were the factors indicating a significantly higher relapse risk; paroxysmal IPS responses, when analyzed in association with these variables, proved to be significant and increased the predictive value for prognosis of associated factors. PMID- 1592071 TI - Paradoxical enhancement of hypoperfusion single photon emission CT images in epileptic focus with bemegride activation. Observation from subtraction of 99mTc hexamethyl-propyleneamine oxime brain single photon emission CT images. AB - Changes of brain images in single photon emission CTs (SPECTs) before and after intravenous injection of bemegride were examined with simultaneous EEG recording in a patient with occipital lobe epilepsy and in a hysteric patient, using a new method, i.e. subtraction of the SPECT images with 99mTc hexamethyl-propyleneamine oxime. The bemegride injection in the epileptic patient paradoxically intensified the hypoperfusion images as epileptic foci in SPECTs, associated with enhanced interictal epileptic discharges, whereas the hysteric showed no such effects. These findings suggest that the hypoperfusion images closely correlate to the severity of epileptic activity, reflecting a functional rather than a morphological deficit. PMID- 1592072 TI - Thiamin contents of cerebrospinal fluid, plasma and erythrocytes in cerebellar ataxias. AB - Free thiamin and thiamin monophosphate have been found in the cerebrospinal fluid, plasma and in erythrocytes of patients suffering from ataxia of different origins. In erythrocytes, thiamin pyrophosphate was also measured. In a limited number of cases, uptake of 14C-thiamin by erythrocytes was found as well. Controls were hospitalized patients affected by chronic neurological diseases without any clinical sign of thiamin deficiency. The results showed a significant decrease in thiamin and thiamin monophosphate in the cerebrospinal fluid and in the plasma of ataxic subjects, in comparison to controls. In erythrocytes, only thiamin pyrophosphate levels had decreased. The uptake of 14C-thiamin by erythrocytes was similar in both ataxic and control groups. These results were comparable to those observed in thiamin-deficient individuals, like alcoholic patients, and prompted further investigation into thiamin metabolism in these diseases. PMID- 1592073 TI - About the mechanism of hiccup. AB - Every new empiric observation made over two millenia fueled the dispute as to whether hiccup (Hc) is a digestive or a respiratory reflex. A review of the literature, focusing attention on the probable mechanism of Hc, shows Hc as a neurogenic dysfunction of the 'valve function' between the inspiratory complex and the glottis closure complex. PMID- 1592074 TI - Comparison of magnetic resonance imaging in Alzheimer's disease, vascular dementia and normal aging. AB - MRI scans of 27 patients with probable Alzheimer's disease (mean age 68.2 years), 31 patients with vascular dementia (mean age 69.9 years) and 18 normal controls (mean age 66.3 years) were compared to evaluate possible distinguishing parenchymal abnormalities among these groups. Atrophy was quantitated by subjective rating, linear and volumetric measurements. A number of findings were significantly more common in vascular dementia than in the other subsets. These included (1) basal ganglionic/thalamic hyperintense foci, (2) thromboembolic infarctions, (3) confluent white matter and (4) irregular periventricular hyperintensities. Signal abnormalities on intermediate T2-weighted scans in the uncal-hippocampal or insular cortex were frequently and almost exclusively noted in Alzheimer's disease. Moderate and severe cortical and ventricular atrophy and a third ventricular to intracranial width ratio larger than 7% were good discriminators between demented groups and normally aging controls. Selective atrophy measurements, however, failed to separate dementia syndromes. These results suggest that MRI has the potential to increase the accuracy of the clinical diagnosis of Alzheimer's disease and vascular dementia. PMID- 1592075 TI - Lipid storage myopathy in multiple acyl-CoA dehydrogenase deficiency: an adult case. AB - A 25-year-old woman had been complaining of episodes of muscle weakness, nausea and vomiting since the age of 10. Muscle biopsy showed free fatty acid accumulation and mitochondrial abnormalities. Mitochondrial DNA appeared to be normal at Southern analysis. Biochemical investigations demonstrated: glutaric aciduria type II, decreased levels of carnitine in liver and values at the lower level of normal in muscle, increased muscle carnitine palmitoyl transferase activity, partial cytochrome c oxidase and succinate cytochrome reductase deficiency in muscle homogenate. In isolated muscle mitochondria, cytochromes aa3, b and c were partially decreased, butyryl-CoA dehydrogenase and palmitoyl CoA dehydrogenase activities were 10 and 54% of the normal, respectively. Muscle cell cultures did not show lipid storage. Low-lipid diet reduced critical episodes and lipid storage in muscle biopsy. PMID- 1592076 TI - Generalization of social skills through self-monitoring by adults with mild mental retardation. AB - The effects of self-monitoring on generalization and maintenance of social skills were investigated. Participants were one female and two male adults with mild mental retardation. A multiple-baseline-across-subjects design with five phases was employed. After an initial baseline condition, the subjects were trained in individualized social skills. Following return to baseline, subjects were taught to self-monitor their behavior, in both training and natural settings. Finally, the use of the self-monitoring device was faded, and all intervention contingencies were withdrawn for the maintenance phase. Data were collected in the analogue and generalization settings throughout all phases of the study. Self monitoring assisted in generalization of trained social skills across settings and people; however, maintenance results were variable. PMID- 1592077 TI - The effects of summarization instruction on text comprehension of students with learning disabilities. AB - This study examined the effectiveness of a summarization strategy for increasing comprehension of expository prose in students with learning disabilities. Thirty students with learning disabilities from Grades 6 through 9 were randomly assigned to experimental and control groups. In addition, 15 students without disabilities served as a normal comparison group for comprehension. Students in the experimental condition were trained to criterion on five rules of summarization. Direct instruction in the summarization strategy significantly increased reading comprehension of the students in the experimental group. Strategy usage was maintained over time, and students were reported to generalize its use. PMID- 1592078 TI - Relationship between measures of adaptive functioning and community adjustment for adults with mental retardation. AB - This study investigated the concurrent relations between measures of adaptive/maladaptive behavior and community adjustment in a sample of 239 adults with mild to severe degrees of mental retardation. Using canonical correlation procedures and multidimensional community adjustment measures, the investigators found significant relations between the measures of behavior and several community adjustment dimensions. The results provided evidence for the criterion related validity of measures of adaptive/maladaptive behavior and suggested that such skills provide an important contribution to community adaptation and to program planning and decision making for individuals with mental retardation. PMID- 1592079 TI - Teacher interactions in mainstream social studies and science classes. AB - This investigation was designed to change teacher-student interactions in middle school social studies and science classes. Eighteen of 35 teacher volunteers received a six-session inservice emphasizing teacher effectiveness variables. Results indicated significant differences between experimental and control teachers on a pre-post contrast, as well as on a follow-up (maintenance) contrast. Differential effects on the science and social studies teachers were seen. Similarities and differences related to student type, independent of the intervention, were obtained. PMID- 1592080 TI - Grade retention rates among students with learning disabilities. AB - This study investigated the grade retention of students with learning disabilities. Data were collected on 689 students referred and identified as having learning disabilities during the 1987-88 school year in Indiana. Of these students, 58% had been retained before identification. The results of this investigation suggest that retention is being used as a remediation before labeling a student. Implications of this practice and alternatives to grade retention as a method to address the academic needs of students are discussed. PMID- 1592081 TI - Specialized instruction within general education: a case study of one elementary school. AB - This study examined how classroom teachers in one elementary school approached the problem of designing specialized instruction for students with reading problems. We asked 12 teachers to rate their confidence in designing effective interventions and then to diagnose a student's reading problem, select an intervention, and implement it. Teachers were moderately confident about their ability to design effective interventions; but some teachers expressed doubts about how to proceed. Their approach to intervention differed somewhat from that of special education resource teachers. Some teachers experienced considerable difficulty in implementing the interventions they selected. PMID- 1592082 TI - Eicosanoid levels in bronchoalveolar lavage fluid of young female smokers and non smokers. AB - To evaluate indicators of inflammatory changes in the airways of young smokers we have measured the levels of several eicosanoids in bronchoalveolar lavage (BAL) fluid of 18 female smokers (age 33 +/- 2 years) and 9 female non-smokers (age 29 +/- 2 years) who were hospitalized for treatment not related to any pulmonary disease. In each BAL specimen the following eicosanoids were determined by radioimmunoassay: prostaglandin (PG) E2; PGF2 alpha; 9 alpha, 11 beta-PGF2, a metabolite of PGD2; 6-keto PGF1 alpha, a metabolite of prostacyclin; thromboxane (Tx) B2, a metabolite of TxA2; the 5-lipoxygenase products 5-hydroxy-eicosa tetraenoic acid (HETE), leukotriene (LT) B4 and LTC4; the 12-lipoxygenase product 12-HETE; and the 15-lipoxygenase product 15-HETE. The concentrations of the cyclooxygenase products (pg ml-1) in the BAL fluid of the non-smokers were: PGE2 15.4 +/- 1.9, PGF2 alpha 7.6 +/- 1.0, 9 alpha, 11 beta-PGF2 8.7 +/- 1.8, TxB2 8.8 +/- 1.3, and 6-keto PGF1 alpha only 1.5 +/- 0.8. The concentration of the lipoxygenase products were: 15-HETE 781 +/- 200, 12-HETE 193 +/- 33, 5-HETE 14.0 +/- 3.1, LTC4 9.5 +/- 3.1, LTB4 6.2 +/- 1.4. BAL fluid from smokers contained two to three-fold higher levels of TxB2 and PGF2 alpha (P less than 0.05). The levels of TxB2 and PGF2 alpha were positively correlated to the number of package years (rs = 0.55 and rs = 0.65, P less than 0.02). The concentrations of 5-, 12- and 15-HETE tended to be higher in BAL fluid from smokers, but this was not significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592083 TI - Affinity of anti-HBs antibody after hepatitis B vaccination. AB - A novel method based on mathematical analysis of the dose-response curve obtained by radioimmunoassay was used to determine anti-HBs affinity and concentration in 29 healthy subjects vaccinated with plasma-derived hepatitis B vaccine. Anti-HBs affinity as well as its serum concentration increased with time in most vaccine recipients; however, the pattern of affinity maturation varied widely between individual subjects. In 20 subjects the highest increase in antibody affinity was observed after the third dose of vaccine, whereas in nine cases values of affinity remained low and relatively constant throughout the time of the study. PMID- 1592084 TI - Effects of hypercholesterolemia on the nucleotide content in human blood cells. AB - In hypercholesterolemia significant changes in the nucleotide pattern of erythrocytes and lymphocytes as determined by high performance liquid chromatography were found. The decrease in ATP of lymphocytes in hypercholesterolemia from 10.4 +/- 0.3 to 7.0 +/- 0.4 nmol mg-1 protein (n = 8) was associated with an increase in ADP from 2.2 +/- 0.2 to 4.0 +/- 0.2 nmol mg-1 protein (P less than 0.005). The pattern of guanosine phosphates likewise was found to be changed in hypercholesterolemia. Akin to lymphocytes, red blood cells displayed marked changes in nucleotide levels. No such changes were observed in platelets. Cultured lymphocytes incubated with human plasma low density lipoproteins (LDL) (140 mg cholesterol dl-1) displayed a reversible fall in ATP and an increase in ADP by about 40% and 160%, respectively, with high density lipoproteins (HDL) or very low density lipoproteins (VLDL) being essentially ineffectual. It is concluded that in hypercholesterolemia a significant change in the nucleotide pattern of blood cells is exerted by the increase in LDL. Possible pathophysiological implications are discussed. PMID- 1592085 TI - Connective tissue response to major surgery and postoperative infection. AB - Type I and type III collagen are components of a healing wound, and major structural proteins. According to our previous study, wound fluid concentrations of the liberated propeptide extensions of procollagens can be used to monitor collagen synthesis in the wound. Serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP), and the aminoterminal propeptide of type III procollagen (PIIINP) were studied here for up to half a year in 102 patients, admitted for major abdominal surgery. In a frequent follow-up (n = 9), one minimum and two maxima were found for S-PICP, occurring 1 day, 7 days, and 2 months after surgery, respectively. S-PIIINP had a minimum at 1 day and a peak at 10 days. Relative changes (follow-up result/pre-operative concentration) of the propeptides in 50 uncomplicated patients were compared. The 1-day minimum of S PICP was 0.60 (SD 0.18), and that of S-PIIINP 0.89 (0.27), (P less than 0.0001, 95% CI for the mean difference 0.21 to 0.36). The 7-day peak of S-PICP was 1.4 (0.5), and that of S-PIIINP 2.5 (1.2), (P less than 0.0001, CI 0.81 to 1.42). The 2-month-peak of S-PICP was 1.6 (0.3), and at the same time the relative S-PIIINP was still 1.7 (0.3) without any separate peak. Major infectious (n = 8) and other (12) complications, exploratory procedures (22) and patients with abnormal pre operative propeptide levels (8) were studied separately. Two early deaths were excluded. Only major infection had a remarkable effect on the responses of S-PICP (3/8) and S-PIIINP (5/8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592086 TI - The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes. AB - Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2-4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apolipoproteins were also documented in pre- and post-clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non-diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 (range 2.3-22.3) in the morning and 9.9 (3.0-22.5) mmol h 1 l-1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 (4.4 30.6) to 10.4 (3.3-31.3) mmol h-1 l-1, P less than 0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P = 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 (9.8 32.7) to 12.6 (6.3-28.3) mmol h-1 l-1, P less than 0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592087 TI - Intrinsic hepatic clearance of indocyanine green in the pig: dependence on plasma protein concentration. AB - Intrinsic hepatic clearance (K) of indocyanine green (ICG) is used as a quantitative measure of liver function. ICG is tightly bound to plasma proteins. The purpose of this study was to examine the effect of changes of plasma protein concentration on K in anaesthetized pigs with intact hepatic circulation. In addition, an attempt was made to evaluate the corresponding changes of the unbound intrinsic clearance of ICG. The plasma protein concentration was changed by exchange of plasma with either dextran-70 or donor pig plasma. Plasma albumin concentration was measured in a peripheral artery and changes of the concentrations of other plasma proteins were assumed to parallel those of albumin. ICG was given as a constant infusion and K was calculated from peripheral artery and hepatic vein concentrations of ICG according to the sinusoidal perfusion model. One experimental series comprised 3 measurement periods: From Period 1 to Period 2 (eight animals) albumin concentration was decreased by 36.6 +/- 6.5% (Mean +/- SD). This was associated with an increase of K of 32.8 +/- 28.8% (P = 0.004). From Period 2 to 3 (five animals) albumin was increased by 13.2 +/- 3.2% and K decreased by 18.5 +/- 8.3% (P = 0.03). In the second experimental series (eight animals), albumin concentration was increased by 21.6 +/- 10.3% and K decreased by 20.3 +/- 8.1% (P = 0.001). For both series, changes in albumin concentration were associated with oppositely directed changes of K in 20 out of 21 comparisons (P less than 0.001). Thus K depends not only on hepatocyte function but also on plasma protein concentration. This finding should affect interpretation of K when used as a liver function test. Changes of the unbound intrinsic clearance of ICG were examined indirectly by means of the K.a product (a: albumin concentration). According to the overall evaluation of the data the unbound intrinsic clearance of ICG was not affected by the changes in plasma protein concentration, but the results were internally inconsistent, apparently due to a time-dependency of the K.a product. We suggest this to be due to a slow but steady decrease of the 'background' K. After correction for the average decrease of K of 0.102% per min our data were in accordance with the hypothesis that the unbound clearance of K was enhanced by the binding protein(s) of ICG. PMID- 1592088 TI - Cellular energetics in hypothyroid muscle. AB - Skeletal muscle of seven hypothyroid patients was investigated in the resting state and during exercise and recovery using 31P magnetic resonance spectroscopy. The bioenergetics and intracellular pH of the hypothyroid muscle were thus evaluated and compared with results from normal muscle and muscle of patients with mitochondrial myopathy. In resting hypothyroid muscle there were significant elevations in the concentration ratios of phosphocreatine/ATP and inorganic phosphate/ATP, while phosphocreatine/inorganic phosphate and intracellular pH were lower than normal. In exercising hypothyroid muscle, energy stores were depleted more rapidly and acidification began later than in normal muscle. Recovery of phosphocreatine to the pre-exercise value was normal, but intracellular pH recovered slowly. The data suggest that in the hypothyroid state, glycogen breakdown in skeletal muscle was delayed thereby limiting the substrate supply for both glycolytic and oxidative production of ATP at the beginning of exercise. There was no evidence for a decrease in the oxidative capacity of the muscle of our patients, but elevated ADP may have stimulated oxidative metabolism and helped to compensate for low mitochondrial content. The low intracellular pH in resting muscle and the slow pH recovery after exercise imply that proton handling was abnormal in the hypothyroid muscle. PMID- 1592089 TI - Bone mass of spine and forearm in osteoporosis and in German normals: influences of sex, age and anthropometric parameters. AB - We measured forearm bone mineral density (BMD) using single photon absorptiometry (SPA) and bone mineral content (BMC) and BMD of lumbar spine by dual photon absorptiometry (DPA). The population consisted of 463 bone healthy subjects, 346 females and 117 males aged 20-85 years. Any underlying bone disease or other diseases known to affect bone mass were excluded by physical examination, thoracic and lumbar radiographs and laboratory screening. Patients with osteoarthritis of lumbar spine were excluded as well as patients taking drugs known to affect bone mass. All bone mass values declined with age. Body height also declined with age by 1.2 cm and 1.8 cm per 10 years (-0.7% and -1%) in females and males respectively. Main effects of age, body height, -surface, weight and -mass index on bone mass were calculated using multiple regression models. In males and females lumbar BMC measured in gHA depended primarily on body height and secondarily on age. Spinal BMD as measured in g cm-2 was primarily dependent on age and then on height. In females forearm BMD depended primarily on age and then on body surface, in males on body surface only. Using receiver operating characteristic (ROC) analysis the ROC area increased from 0.81 0.85 (n.s.) including body height into spinal BMD values leading to a higher sensitivity of measurements of spinal bone mass in recognizing 58 patients with spinal postmenopausal osteoporosis. Including body surface into forearm BMD measurements ROC area increased from 0.66-0.69 (P = 0.055).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592090 TI - Experimental onchocerciasis in chimpanzees. Antibody response and antigen recognition after primary infection with Onchocerca volvulus. AB - Nine of 18 chimpanzees inoculated with 250 infective third-stage larvae (L3) each developed patent (i.e., positive for microfilariae) Onchocerca volvulus infection. Four of 6 infected chimpanzees that received 200 micrograms/kg ivermectin at 28 days postinfection (pi) became patent, whereas, when ivermectin was given concurrently with L3 challenge only 1 of 6 infected animals developed patent infection. The antibody response to O. volvulus adult worm-derived antigens (OvAg) showed clear differences between patent and nonpatent chimpanzees. Three months pi, all sera detected several OvAg in the range of M(r) 35-120 k. Sera collected 6 mo pi from later patent animals recognized increasing numbers of OvAg, especially in the lower MW range of M(r) 13 to 33 k. Beginning 10 months pi Onchocerca-antigens of M(r) 21, 24, 26, and 28 k were detected only by patent chimpanzee's sera. The antibody response in nonpatent chimpanzees consistently recognized fewer OvAg, most of which were limited to the higher M(r) range (35-120 k). The reactivity of sera from infected chimpanzees to a low molecular weight fraction (LMW) of total OvAg doubled within 6 months pi, and increased continuously in patent animals from 13 until 30 months pi. Serological reactivity of nonpatent animals to LMW-OvAg remained low. The titers of circulating IgG directed against total OvAg increased in all infected chimpanzees, and continued to rise with patency. In nonpatent chimpanzees the antibody production gradually returned to preinfection values. Total and OvAg specific IgE increased in patent and nonpatent chimpanzees. Also, during prepatency the granulocyte and antibody-mediated in vitro killing of microfilariae of O. volvulus increased in subsequently patent chimpanzees. The in vitro immobilization of L3 remained low. PMID- 1592091 TI - Plasmodium falciparum: the repetitive MSA-1 surface protein of the RO-71 isolate is recognized by mouse antibody against the nonrepetitive repeat block of RO-33. AB - We have expressed in Escherichia coli the nonrepetitive repeat zone of the MSA-1 surface protein of the RO-33 isolate of Plasmodium falciparum. The recombinant protein was used to immunize mice and the resulting RO-33 monospecific serum was used to screen our P. falciparum strain collection in order to recover additional alleles lacking tripeptide repeats in block 2 of MSA-1. Only 1 (RO-71) out of 30 isolates tested reacted strongly with the serum by indirect immunofluorescence assay. Surprisingly, block 2 of the RO-71 MSA-1 allele contains tripeptide repeats resembling those of the K1 isolate of P. falciparum. Additional sequence analysis of the entire DNA coding for the 80-kDa MSA-1-derived surface component did not reveal any amino acid stretches similar to block 2 of RO-33 which could rationalize the immunological cross-reactivity. We eliminated the possibility that the RO-71 culture was contaminated with RO-33 type alleles of MSA-1 by Southern blotting and PCR analysis. The RO-33-specific mouse serum used for the initial selection of RO-71 did not react with the antigen in the denatured state (Western blot). This and the sequence analysis suggest that the cross-reactive epitope in the MSA-1 protein of RO-71 is conformational. The possibility that a truncated frame-shift protein encoded by mutated MSA-1 mRNA is recognized by the serum is discussed. PMID- 1592092 TI - Fasciola hepatica: molecular cloning, nucleotide sequence, and expression of a gene encoding a polypeptide homologous to a Schistosoma mansoni fatty acid binding protein. AB - Immunization of mice with an antigenic polypeptide from Fasciola hepatica adult worms and having an apparent molecular mass of 12,000 Da (Fh12) has been shown to reduce the worm burden from challenge infection with Schistosoma mansoni by more than 50%. Moreover, mice infected with S. mansoni develop antibodies to Fh12 after 5-6 weeks of infection, indicating that this Fasciola-derived antigen is a cross-reactive, cross-protective protein. A lambda gt11 F. hepatica cDNA library was constructed from poly(A)+ RNA extracted from adult worms. A cDNA encoding a cross-reactive polypeptide (Fh15) was cloned by screening the F. hepatica lambda gt11 library with a monospecific, polyclonal rabbit antiserum against pure, native Fh12. The cDNA was sequenced and the predicted amino acid sequence revealed an open reading frame encoding a 132-amino-acid protein with a predicted molecular weight of 14,700 Da. This protein has significant homology to a 14-kDa S. mansoni fatty acid-binding protein. Comparison of the protective-inducing activity of recombinant Fh15 with that of purified Fh12 against schistosomes and Fasciola is warranted. PMID- 1592093 TI - Trichinella spiralis: evidence that mice do not express rapid expulsion. AB - The rapid expulsion of Trichinella spiralis by mice of a variety of inbred and F1 mouse strains was examined. Mice were reinfected once with T. spiralis during and immediately after the natural termination of a primary infection and worm rejection was measured less than or equal to 24 hr after the challenge. The results showed that the challenge (super)infection was consistently rejected by all mouse strains before rejection of the adult worms from the primary infection commenced. Rejection of the challenge infection began at different times after the primary infection with NFS (2 days) less than C3H less than or equal to B10.Q approximately B10.BR (greater than 5 days). In all strains, rejection of the challenge infection preceded adult worm rejection from the primary infection by 5 8 days. At its peak, the loss of challenge worms related directly to the strength of the primary rejection process NFS greater than or equal to 98%, C3H 90-98%, and B10 mice 80-90%. Furthermore, loss of the capacity to reject the challenge followed approximately 7 days after the complete loss of the primary infection in each strain examined. Thus, the sooner worms from the primary infection were lost, the earlier the capacity to promptly reject the challenge infection disappeared. B10.Br mice still partially rejected a superinfection 35 days after the primary infection began, whereas NFS mice lost this capacity around 25 days. However, premature termination of the primary infection in B10.BR mice with methyridine at the same time that NFS mice naturally terminated their infection (15 days) abrogated the capacity of B10.BR mice to reject the superinfection at 24 days. Passive transfer of protective rat IgG monoclonal antibody to mice did not lead to rapid expulsion. Transfer of mouse immune serum to intestinally primed rats did result in rapid expulsion, suggesting that mouse antibody responses were adequate. The expression of superinfection rejection was susceptible to the administration in vivo of GK1.5, anti-mouse L3T4 antibody. The data indicate that the principal determinant of the strength, time of initiation, and longevity of rejection of a challenge infection was the response to the primary infection of that individual mouse strain. The genetic determinants of challenge infection rejection were seen to be identical to those that determined rejection of the primary infection. Since no evidence could be found to support the identity of this response with rapid expulsion, as defined in rats, a new term, "associative expulsion," is proposed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592094 TI - Eimeria tenella: growth and drug sensitivity in tissue culture under reduced oxygen. AB - For Plasmodium falciparum in culture, growth is enhanced as oxygen tension is lowered and drug susceptibility, particularly susceptibility to 70S ribosomal and mitochondrial inhibitors, changes. Whether similar effects occur in Eimeria tenella was tested as a possible explanation for why certain 70S ribosomal inhibitors, while active in Eimeria-infected birds, are virtually inactive in vitro under ambient oxygen conditions. It was reasoned that perhaps these agents would exhibit good in vitro potency under reduced oxygen conditions. Such proved not to be the case, and it was further found that no positive effect on Eimeria growth occurred under these conditions. Finally, lowering oxygen tension had no substantial effects on sensitivity to anticoccidials or mitochondrial inhibitors. PMID- 1592096 TI - The effects of HIV on hematopoiesis. AB - Hematologic abnormalities are commonly associated with infection by the human immunodeficiency virus (HIV) that is the etiologic agent of the acquired immunodeficiency syndrome (AIDS). Bone marrow examinations reveal frequent dysplasia, dyserythropoiesis, lymphocytic infiltration and plasmocytosis. These marrow morphologic characteristics are strongly associated with peripheral blood cytopenia of one or more lineage: anemia, granulocytopenia or thrombocytopenia are frequently described. The pathophysiology of these observed deficiencies is still unclear, although several mechanisms have been postulated as possible explanations for the hematological features of AIDS patients. The hematologic manifestations observed in patients with AIDS or AIDS-related complex (ARC) and the postulated pathogenetic mechanisms are discussed in this review. PMID- 1592095 TI - Plasmodium falciparum: rapid detection of dihydrofolate reductase mutations that confer resistance to cycloguanil and pyrimethamine. PMID- 1592097 TI - Phenotypic and genotypic switch in Philadelphia-positive, BCR-positive blast crisis of chronic myeloid leukemia. AB - We report a case of Ph1-positive, bcr-positive chronic myeloid leukemia blast crisis (CML-BC) which at presentation showed a mixed myeloid/B-lymphoid immunophenotype along with TdT positivity and, at the molecular level, an oligoclonal rearrangement of the immunoglobulin heavy chain (IgH) gene region. After obtaining a successful remission, at the time of relapse the patient underwent a phenotypic and genotypic switch from mixed to myeloid phenotype, characterized by the loss of the lymphoid markers and TdT expression and by a germline configuration of the IgH gene region. The same bcr rearrangement was, however, found in both phases of the disease, supporting the suggestion of a true phenotypic and genotypic conversion. This report confirms that the neoplastic event in CML may take place at an early multipotent stem-cell level, prior to a well-defined phenotypic and genotypic lineage expression. Moreover, it is suggested that different factors (chemotherapy? growth factors?) may have either eradicated the bcr+/IgH+ clone and promoted the growth of bcr+/IgH- leukemic cells or, alternatively, supported the lymphoid differentiation program and induced a myeloid lineage shift. PMID- 1592098 TI - Occurrence of monoclonal components in general practice: clinical implications. AB - We report on the occurrence of monoclonal components observed in a provincial hospital in northern Italy from 1987 to 1990. The monoclonal components were detected by visual inspection of high-resolution acetate serum electrophoreses and typed by immunofixation. The percentage of monoclonal components increases steeply with age, and reaches a plateau of 7-8% in individuals over 55 years old. Besides the high percentage of monoclonal component, the other relevant finding of this study is that approximately 80% of monoclonal components are of low concentration (less than 5 g/l). Most of these subjects with small monoclonal component passed undetected in the previous studies on the prognostic significance of monoclonal gammapathy. These findings indicate the need for a revision of the current concepts on the biological and clinical significance of MC discovered by chance. PMID- 1592099 TI - Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin activated platelets. AB - The effect of thrombin-activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura-2. [Ca2+]i of PMNs was transiently elevated by thrombin-activated platelets. The supernatant of thrombin-activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 mumol/l adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin-activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin-sensitive factor(s). PMID- 1592100 TI - In vivo kinetics of 111indium-labelled autologous granulocytes following i.v. administration of granulocyte-macrophage colony-stimulating factor (GM-CSF). AB - Administration of both glycosylated and non-glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) induces an immediate transient granulocytopenia of 1-3 hours' duration. In order to explore this phenomenon, granulocytes were labelled with 111Indium and the effect on the kinetics of granulocytes after administration of rhGM-CSF was studied in 10 previously untreated patients with malignant lymphoma. For both types and doses of rhGM-CSF, a significant and dramatic accumulation of the 111Indium-labelled granulocytes was observed in the lung within a few minutes after i.v. injection of rhGM-CSF. The accumulation of radioactivity coincided with the pronounced and transient granulocytopenia in peripheral blood. The 111Indium-labelled granulocytes later reappeared in the peripheral blood, indicating reversible pulmonary vascular margination of the granulocytes. Half-life of labelled granulocytes after reappearance was comparable to half-life values under normal conditions. The transient accumulation of granulocytes in the pulmonary vessels seems not to be of clinical importance in the management of patients, but it may to some degree explain previously described side-effects, such as transient hypoxemia ("first-dose" reaction) following administration of rhGM-CSF. PMID- 1592101 TI - Myelofibrosis in primary myelodysplastic syndromes: a retrospective study of 352 patients. AB - In a retrospective study of 352 patients with primary myelodysplastic syndromes, 61 (17.3%) revealed myelofibrosis in bone marrow biopsies. The fibrosis was observed to occur mostly focally (41/61 cases), and collagen deposits were found very rarely (4/61). The histopathology of bone marrow biopsies revealed hyperplasia and disturbed differentiation in megakaryopoiesis; the frequency and grade of dysplasia in megakaryopoiesis increased with advancing myelofibrosis. Reticulin fibrosis occurred in all subtypes of MDS; however, there was a higher incidence in chronic myelo-monocytic leukaemia (CMMoL). The frequency of cytogenetic aberrations was significantly higher in the MDS cases with myelofibrosis, compared to the cases without fibrosis. Clinical data showed significantly lower values of haemoglobin and lower platelet counts in MDS with myelofibrosis. Life expectancy was reduced to 9.6 months, compared with 17.4 months in MDS without fibrosis. In refractory anaemia, the survival times were 10.0 months in MDS with myelofibrosis, compared to 28.9 months in MDS without myelofibrosis. 36.6% of the patients with MDS and myelofibrosis developed a transformation into ANLL during the course of the disease. Myelofibrosis therefore seems to herald a poor prognosis. PMID- 1592102 TI - High remission rate in acute myeloblastic leukemia in children treated with high dose methylprednisolone. AB - Since the differentiating effect of high-dose methylprednisolone (HDMP) on myeloid leukemic cells has been shown in one of our patients with acute myeloblastic leukemia (AML-M4), 27 previously untreated children with AML were given HDMP (20-30 mg/kg per day) combined with cytosine arabinoside (Ara-C; 3 mg/kg) for the first 2 weeks of induction therapy. Marked clinical improvement was observed in all patients with the exception of one who died within 24 hours of the treatment. Enlarged liver and spleen (greater than 5 cm) became nonpalpable in 3 (37%) out of 8 and 5 (100%) out of 5 patients, respectively, and bone marrow blasts decreased below 5% in 7 patients (27%) within 2 wk of HDMP and Ara-C treatment. Adriamycin (1 mg/kg) was added 2 wk after initiation of induction therapy. Twenty-two (84.6%) of the 26 patients achieved complete remission, 3 (11.5%) had partial remission and no response was obtained in one. Treatment was well tolerated. The addition of HDMP as a differentiating and/or cytolytic agent to conventional anti-leukemic chemotherapy increased the complete remission rate and prolonged the duration of remission of our AML patients. PMID- 1592103 TI - Cobalamin binding proteins in patients with HIV infection. AB - P-Cobalamins have been reported to be decreased in patients with HIV infection. Because of this, we found it of interest to examine both cobalamin-saturated binding proteins (holo-transcobalamin, holo-TC and holo-haptocorrin, holo-HC) and cobalamin unsaturated binding proteins (apo-transcobalamin, apo-TC and apo haptocorrin, apo-HC). The results are given as range and (median). Eighteen male HIV-infected patients with plasma cobalamins below 200 pmol/l were studied. We found low concentrations of holo-TC (37-88 (47.5) pmol/l) and holo-HC (64-184 (135.5) pmol/l). The concentration of apo-TC and apo-HC was increased (480-1730 (1025) pmol/l; 70-800 (235) pmol/l). It is concluded that, in HIV-infected patients, low plasma cobalamin does not reflect a low concentration of transcobalamin or haptocorrin. In 20 HIV-infected patients and 31 patients with malignant haematological diseases, the TC isopeptide patterns were determined. In the HIV group, an increased frequency of TC isopeptide X was found and the overall distribution of TC isopeptides was significantly different from the reference population (p less than 0.05). There was no difference between the group of patients with malignant haematological diseases and the reference group. PMID- 1592104 TI - Iron status in white sickle cell disease patients. PMID- 1592105 TI - Cysteine reactivity in sorbitol and aldehyde dehydrogenases. Differences towards the pattern in alcohol dehydrogenase. AB - In sorbitol dehydrogenase only one cysteine residue, Cys-43, is reactive in both anionic buffer (phosphate) and zinc-liganding buffer (imidazole) upon carboxymethylation. This is in contrast to the situation in the structurally related liver alcohol dehydrogenase, with either of two alternative Cys residues being reactive, and is compatible with differences in zinc-binding and active site relationships between these two metalloenzymes. Unrelated aldehyde dehydrogenase, upon carboxamidomethylation, shows a third pattern, now less well defined but confirming the presence of a thiol function of Cys-302 close to the active site. PMID- 1592106 TI - Comment to Shinohara et al. (1991) FEBS Letters 293, 173-174. The uncoupling protein is not expressed in rat liver. AB - Using Northern blot analysis, immunoblotting with purified antibodies and Polymerase Chain Reaction analysis, we were unable to detect the Uncoupling Protein-UCP or its mRNA in liver of control, cold-exposed or newborn rats. The unique expression of this protein in brown adipocytes was confirmed. These data refute the surprising recent report on UCP expression in rat liver (Shinohara (1991) FEBS Lett. 293, 173-174). Moreover we report that the hybridization signal obtained by these authors is probably non-specific and due to the 3' non-coding domain of the UCP cDNA probe. PMID- 1592107 TI - Efficient in vitro folding of the three-disulfide derivatives of hen lysozyme in the presence of glycerol. AB - Four derivatives of hen lysozyme, each lacking one native disulfide bond of the four in authentic lysozyme, were produced in Escherichia coli by expressing synthetic mutant genes. In the reoxidation reaction of the reduced derivatives purified from inclusion bodies, the addition of glycerol significantly enhanced the efficiency of folding and 'correct' disulfide bond formation. This enabled simple chromatographical purification of refolded materials. Purified 3SS derivatives all showed lytic activities and secondary structures comparable to authentic lysozyme, which directly showed that none of the four native disulfide bonds is a prerequisite for 'correct' in vitro folding. PMID- 1592108 TI - Tumorigenicity-associated expression of protein kinase C isoforms in rhabdomyosarcoma-derived cells. AB - Cell sublines were derived from Ni-induced rat rhabdomyosarcoma which differed in their degree of tumorigenicity. We compared the expression of protein kinase C isoforms alpha, beta, gamma and epsilon in three sublines developing tumors in syngeneic rats (Sy+) and in two sublines devoid of tumorigenicity in these animals (Sy-), with that of normal skeletal muscle. Northern and Western blotting experiments showed that PKC alpha was dramatically overexpressed in Sy- cells whereas it was underexpressed in Sy+ cells. Southern blot analysis provided evidence for a 3-fold increase of PKC alpha-related DNA fragments in Sy- cells. Steady-state levels of the PKC epsilon-related transcript were also markedly decreased in Sy+ cells. However, the expression of PKC beta-related RNA was increased in these cells. Our data support the concept that the differential expression of the PKC isoforms may play a critical role in determining the neoplastic phenotype. PMID- 1592110 TI - Specific binding of phenolic glycolipid antigens from Mycobacterium bovis BCG with antibodies. AB - We studied the molecular binding specificity of two rabbit polyclonal sera generated against phenolic glycolipid antigens namely PheG1 B and PheG1 B-3 from Mycobacterium bovis BCG. PheG1 B is the well-known mycoside B (2-O-Me-alpha-L Rhap 1----aglycone), while PheG1 B-3 is a recently found glycolipid (alpha-L-Rhap (1----3)-2-O-Me-alpha-L-Rhap 1----aglycone). The interaction specificity was mainly explained in terms of the cavity volume of the antibodies paratope. The anti-PheG1 B antibodies paratope fits the 2-O-Me-alpha-L-Rhap ligand, while that of anti-PheG1 B-3 binds the disaccharide moiety of PheG1 B-3, and, with a higher affinity, the monosaccharidic unit localized at the non-reducing end. The B-3 antigen affinity is higher than that of antigen B for their homologous antibodies. This can be explained by the fact that the antibodies against phenolic glycolipid B-3 bind optimally to two sequential glycosyl residues suggesting the presence of two subsites. The immunoglobulin subsite with the major affinity binds the monosaccharidic unit localized at the non-reducing end. PMID- 1592109 TI - H7, a protein kinase C inhibitor, increases the glutathione content of neuroblastoma cells. AB - It is shown that the intracellular glutathione (GSH) concentration of neuroblastoma-2a cells in culture increases with a maximum at 24 h after starting treatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), an inhibitor of protein kinase C (PKC). Other inhibitors of this and other protein kinases, e.g. sphingosine, staurosporine, and HA 1004, at the concentrations tested, had a less marked or negligible effect on intracellular GSH concentration. 12-O Tetradecanoylphorbol-13-acetate (TPA) was also tested and showed no significant effect 24 h after addition. PMID- 1592111 TI - Isolation of a thermostable enzyme catalyzing disulfide bond formation from the archaebacterium Sulfolobus solfataricus. AB - A disulfide bond-forming enzyme was purified from the cytosol of the archaebacterium Sulfolobus solfataricus, strain MT-4. The enzyme, assayed by its ability to oxidize and reactivate reductively denatured ribonuclease A, had a small molecular size and displayed a high thermostability. The N-terminal amino acid sequence is reported. PMID- 1592112 TI - Structure of the guinea pig neutrophil cationic peptide gene. AB - Guinea pig neutrophils contain the antimicrobial cationic peptides GNCP-1 and GNCP-2 in the granules. In this study, the GNCP gene was isolated, and the structure was characterized. Using cDNA probes, one phage clone was isolated from a guinea pig genomic library. The gene spanned greater than 3 kb, and comprised three exons and two introns. Sequence analysis revealed that the gene encoded GNCP-2. Exon 1 mainly coded for the 5' untranslated region, exon 2 coded for the prepro-peptide region of GNCP-2, and exon 3 coded for the mature peptide region of GNCP-2 and the 3' untranslated region. Primer extension analysis indicated that the transcription initiation site was located to a thymidine residue, 93 bp upstream of the ATG initiation codon of GNCP-2 mRNA. A possible TATA box was located 24 bp upstream of the transcription start site. Interestingly, the pyrimidine-rich sequences identified in the promoter regions of the human neutrophil elastase and myeloperoxidase genes were also found in the 5' flanking region of the GNCP-2 gene. PMID- 1592113 TI - Cloning and characterization of the cDNA encoding human adenylosuccinate synthetase. AB - Adenylosuccinate synthetase (AS) catalyzes the first committed step in the conversion of IMP to AMP. A cDNA was isolated from a human liver library which encodes a protein of 455 amino acids (M(r) of 49,925). Alignments of human, mouse, Dictyostelium discoideum and E. coli AS sequences identify a number of invariant residues which are likely to be important for structure and/or catalysis. The human AS sequence was also 19% identical to the human urea cycle enzyme, argininosuccinate synthetase (ASS), which catalyzes a chemically similar reaction. Both human liver and HeLa AS mRNA showed signals of 2.3 and 2.8 kb. An unmodified N-terminus is required for function of the human AS enzyme in E. coli mutants lacking the bacterial enzyme. The human cDNA provides a means to assess the possible role of AS abnormalities in unclassified, idiopathic cases of gout. PMID- 1592114 TI - Characterization of site-directed mutations in conserved domains of MalK, a bacterial member of the ATP-binding cassette (ABC) family [corrected]. AB - Site-directed mutagenesis was used to change four amino acid residues (Q82, P152, L179, H192) in the MalK subunit of S. typhimurium maltose transport system which are highly conserved among members of the ATP-binding cassette (ABC) family. Replacement of H192 caused complete failure to complement the transport defect of a malK strain whereas changes of the other residues resulted in reduced or wild type activity. The purified mutant proteins exhibited ATPase activity comparable to wild-type MalK. PMID- 1592115 TI - Aerobic heat shock activates trehalose synthesis in embryos of Artemia franciscana. AB - Encysted embryos (cysts) of the brine shrimp, Artemia franciscana, contain large amounts of trehalose which they use as a major substrate for energy metabolism and biosynthesis for development under aerobic conditions at 25 degrees C. When cysts are placed at 42 degrees C (heat shock) these pathways stop, and the cysts re-synthesize the trehalose that was utilized during the previous incubation at 25 degrees C. Glycogen and glycerol, produced from trehalose at 25 degrees C, appear to be substrates for trehalose synthesis during heat shock. Anoxia prevents trehalose synthesis in cysts undergoing heat shock. These results are consistent with the view that trehalose may play a protective role in cells exposed to heat shock, and other environmental insults, in addition to being a storage form of energy and organic carbon for development. PMID- 1592116 TI - Three-dimensional structural resemblance between leucine aminopeptidase and carboxypeptidase A revealed by graph-theoretical techniques. AB - Using 3-D searching techniques based on algorithms derived from graph theory we have established a striking structural similarity between the structure of bovine carboxypeptidase A and that of the C-terminal domain of bovine leucine aminopeptidase. There is no significant sequence homology between the aminopeptidases and the carboxypeptidases but the strong structural relationship detected in this complex fold suggests that there may be a very remote divergent evolutionary relationship between these two enzyme classes. PMID- 1592117 TI - Affinity labeling of GTP-binding proteins in cellular extracts. AB - GTP-binding proteins in cellular extracts from Escherichia coli, Thermus thermophilus, yeast, wheat germ or calf thymus were identified using in situ periodate-oxidized [alpha-32P]GTP as affinity label. Site-specific reaction of individual GTP-binding proteins was achieved by cross-linking the protein-bound 2',3'-dialdehyde derivative of GTP with the single lysine residue of the conserved NKXD sequence through Schiff's base formation and subsequent cyanoborohydride reduction. Labeled GTP-binding proteins from prokaryotic or eukaryotic cell homogenates were separated by polyacrylamide gel electrophoresis and visualized by autoradiography. In addition cross-linking of [alpha-32P]GTP with GTP-binding proteins was demonstrated in model systems using different purified GTPases, human c-H-ras p21, transducin from bovine retina, polypeptide elongation factor Tu (EF-Tu) from T. thermophilus and initiation factor 2 (IF2) from T. thermophilus. The described affinity labeling technique can serve as an analytical method for the identification of GTPases belonging to the classes of ras-proteins, elongation and initiation factors, and heterotrimeric signal transducing G-proteins. PMID- 1592118 TI - Class IV alcohol dehydrogenase (the gastric enzyme). Structural analysis of human sigma sigma-ADH reveals class IV to be variable and confirms the presence of a fifth mammalian alcohol dehydrogenase class. AB - Human gastric alcohol dehydrogenase (sigma sigma-ADH) was submitted to peptide analysis at picomole scale. A total of 72 positions were determined in the protein chain, providing information on three aspects of alcohol dehydrogenase structures in general. First, the data establish the presence of a unique class of the enzyme, now confirmed as class IV, expressed in gastric tissue and separate from another novel class, now termed class V. Second, the class IV gastric enzyme has active site relationships compatible with an ethanol-active, zinc-containing alcohol dehydrogenase. Third, this enzyme class is of the variable type, like that for the 'variable', classical liver alcohol dehydrogenase of class I, and in contrast to that for the 'constant' class III enzyme. Known human alcohol dehydrogenase structures now prove the presence of at least seven human genes for the enzyme and nine for the whole protein family. PMID- 1592119 TI - Effects of 2(3)-tert-butyl-4-hydroxyanisole (BHA) on in situ mitochondria of Trypanosoma cruzi. AB - Results obtained with in situ mitochondria of Trypanosoma cruzi showed that this protozoon had only two energy coupling sites, sites II and III that correspond to higher eukaryote mitochondria. Rotenone did not inhibit the oxygen uptake of the parasite. These results suggest that the NADH-ubiquinone segment of the respiratory chain has no activity. Studies with in situ mitochondria confirmed that BHA, an antioxidant food additive, blocks the mitochondrial electron transport chain at the succinate-cytochrome b segment being the molecular basis of this trypanocidal action. PMID- 1592120 TI - IL-1 beta, a strong mediator for glucose uptake by rheumatoid and non-rheumatoid cultured human synoviocytes. AB - Higher basal 2-deoxy-D-glucose uptake in rheumatoid synovial cells than in non rheumatoid synovial cells, was found to be associated with an increased interleukin-1 beta (IL-1 beta) secretion (respectively 850 +/- 238 vs. 8.3 +/- 2.4 pg/24 h/10(5) cells, mean +/- S.E.M.). When exogenous human recombinant IL-1 beta was added to cultures, a marked stimulation of 2-deoxy-D-glucose uptake was performed by both human synovial cultured cells, in a time-dependent and dose dependent manner (IL-1 beta 0-100 ng/ml). In non-rheumatoid synoviocytes, stimulation occurred 1-3 h following the addition of 1 ng/ml interleukin-1 beta and increased up to 24 hours (respectively +150% and +261.4% after 6 and 24 hours association time). Rheumatoid synovial cells were less sensitive to 1 ng/ml IL-1 beta (respectively +80% and +146.4%). IL-1 beta increased significantly the Vmax for 2-deoxy-D-glucose uptake by synovial cells, with no change in the Km. This effect was protein synthesis-dependent, and not secondary to prostaglandin E2 synthesis or cell growth. IL-1 beta possesses an important effect on glucose homeostasis in synovial cells, which could be indirect and/or regulated by the presence of natural inhibitors. PMID- 1592121 TI - Protein kinase C activity affects glucose-induced oscillations in cytoplasmic free Ca2+ in the pancreatic B-cell. AB - Acute stimulation of protein kinase C (PKC) inhibited glucose-induced slow oscillations in cytoplasmic free Ca(2+)-concentration, [Ca2+]i, in mouse pancreatic B-cells. In PKC-depleted cells glucose induced rapid transients in [Ca2+]i, lasting for approximately 10 s, superimposed on the slow oscillations in [Ca2+]i. It was demonstrated that the transients did not occur in the absence of extracellular Ca2+. Each transient typically was preceded by a slow increase in [Ca2+]i, representing the rising phase of an ordinary glucose-induced slow oscillation, and the [Ca2+]i, immediately after a transient was lower than just before the spike. These data further emphasize the interplay between voltage dependent Ca(2+)-channels and the phospholipase C system in the regulation of B cell [Ca2+]i-oscillations. PMID- 1592122 TI - Crystallization and preliminary X-ray analysis of recombinant human transforming growth factor beta 2. AB - Recombinant human transforming growth factor beta 2 (TGF-beta 2) was cloned and expressed in E. coli. The protein was isolated from inclusion bodies, renatured and purified to a single component as judged by reversed-phase HPLC. The recombinant TGF-beta 2 was shown to have a biological activity equal to that of native TGF-beta 2 in a fibroblast migration assay. Pure, active recombinant TGF beta 2 has been crystallized from polyethylene glycol 400. The trigonal crystals of spacegroup P3(1)21 or P3(2)21 have unit cell dimensions of a=b=60.6 A, c=75.2 A and diffract beyond 2.0 A. PMID- 1592123 TI - Carotid endarterectomy: future perspectives. PMID- 1592124 TI - Colour flow imaging in the detection of femoro-distal graft and native artery stenosis: improved criteria. AB - Vein graft or native artery stenosis after femoro-distal revascularisation is a common cause of graft occlusion. The early detection and treatment of such stenoses offers the potential for better graft patency than salvage procedures undertaken for graft thrombosis. In the past, two criteria using duplex scanning have been used to detect grafts at risk: (a) a localised increase in the peak velocity (V2) by 100% or more in comparison to the peak velocity (V1) 2 cm upstream (i.e. V2/V1 ratio greater than 2.0), and (b) a decrease in average peak velocity to less than 45 cm s-1. Seventy-four consecutive patients with femoro distal vein grafts have been studied with intravenous digital subtraction angiography to detect stenosis (greater than 50% diameter) and colour flow imaging using both duplex scanning criteria (a) and (b) at 1.5, 3, 6, 9 and 12 months after operation. The results show that the V2:V1 ratio greater than criterion had a sensitivity of 100% and a specificity of 83%. Stenoses in the native distal arteries were not detected. Low average peak velocity less than 45 cm s-1 had a sensitivity of 61% and a specificity of 98%. By combining both criteria the sensitivity for detecting stenoses in both the vein graft and native distal artery, became 100% and the specificity 98%. PMID- 1592125 TI - Accelerated thrombolysis using pulsed intra-thrombus recombinant human tissue type plasminogen activator (rt-PA). AB - The efficacy of regional thrombolysis for treating leg ischaemia is well established, but the duration of infusion and the frequent complications remain major disadvantages. By delivering recombinant human tissue type plasminogen activator (rt-PA) as pulsed intra-thrombus 5-mg aliquots combined with catheter manipulation to maintain an intra-thrombus location, the average time taken to achieve thrombolysis in 20 consecutive patients with infra-aortic occlusions was 109 min. Immediate thrombolysis was achieved in every case. Pulsed delivery of high dose rt-PA significantly accelerates thrombolysis, decreases dose and reduces costs. PMID- 1592126 TI - Hypoxic ventilatory response and carotid endarterectomy. AB - Carotid endarterectomy is reported to abolish hypoxic ventilatory responsiveness. This effect is thought to be due to denervation or destruction of the carotid bodies by surgical exposure. The technique of carotid endarterectomy, however, does not require the sacrifice of these structures. Six patients who had bilateral carotid endarterectomy with careful preservation of the carotid bodies and their innervation were studied pre- and postoperatively with respect to hypoxic ventilatory responsiveness and the latter was taken as a measure of chemoreceptor activity. Five patients showed a weak or absent response to hypoxia before surgery. In four of these there was a significant increase in reactivity after the procedure (p less than 0.01 in one case, p less than 0.05 in three others). The fifth patient had a non-significant increase and the sixth had a normal response before and after surgery. Thus, loss of chemoreceptor function after bilateral carotid endarterectomy was not observed in this group of patients with preserved carotid bodies. The low ventilatory hypoxic sensitivity before surgery and its occasional increase after removal of the plaque suggests that atherosclerosis might well impair the microscopic blood supply to the carotid bodies, inducing sensor dysfunction but this hypothesis requires further investigation. PMID- 1592127 TI - Aetiology of chronic leg ulcers. AB - This study was undertaken to determine the relative prevalence of the factors causing chronic ulceration of the leg in the general population. Two hundred and fifty-nine patients with chronic ulceration of the leg were found on screening a Western Australian population of 238,000. (The prevalence of chronic ulceration of the leg was 1.1 per 1000 population.) Two hundred and forty-two of these patients (93%) with 286 chronically ulcerated limbs were fully assessed to determine the factors contributing to ulceration. In 239 limbs (84%) ulceration involved the leg; in these limbs venous disease was the most prevalent cause of ulceration (160 limbs). Arterial disease was found in 66 limbs, with both venous and arterial disease present in 35 limbs. Rheumatoid arthritis was a causative factor in 27 limbs and diabetes was found with 29 limbs with ulceration involving the leg. In 47 limbs (16%) ulceration was confined to the foot; arterial disease (35 limbs) and diabetes (23 limbs) were the most prevalent causes of ulceration in these limbs. Venous disease was infrequent (three limbs). No disorder of the circulation was found in 48 limbs (20%) with ulceration involving the leg, and in 58 (20%) of all ulcerated limbs. More than one aetiological factor was present in 93 limbs (33%). A cause for ulceration was not found in 10 limbs (3.5%). PMID- 1592128 TI - Axillo-femoral bypass and simultaneous removal of the aorto-femoral vascular infection site: is the procedure safe? AB - In a retrospective analysis 12 patients treated for aorto-femoral vascular infections between 1984 and 1990 were evaluated. They were all male with a mean age of 63 years. Indications for treatment were: mycotic aneurysms-3, primary aorto-enteric fistula-2 and graft infection-7. Surgical treatment consisted of implantation of an extra-anatomic bypass, carefully avoiding the infected area, followed by removal of the infected graft and tissue at the same session. There was no early mortality (less than 30 days) but the first year mortality was 42% (n = 5). Causes of death were: aortic stump disruption (n = 1), recurrence of aorto-enteric fistula (n = 2), axillary anastomosis disruption (n = 1), cardiac failure (n = 1). Orthotopic reconstruction of the aorta after 12 months, as we advocate, was accomplished in two patients and is scheduled in another one. In two patients their poor condition precluded this second step, and in two further patients above-knee amputation with subsequent extra-anatomic graft removal was needed. Only one of the 12 extra-anatomic bypasses became infected. Reconstruction by axillo-femoral bypass combined with removal of the aorto femoral graft at the same session is a practicable procedure with good early results. However, the rate of successful orthotopic reconstruction of the aorta after 12 months is low because of a high mortality rate, especially in the presence of aorto-enteric fistulas, and because some patients with well functioning axillo-femoral grafts are in too poor condition for another large operation. PMID- 1592129 TI - Use of descending thoracic aorta for lower limb revascularisation. AB - From November 1984 to May 1991, descending thoracic aorta to femoral artery bypass was used to revascularise 51 lower limbs in 27 patients. There were 25 men and 2 women with a mean age of 60.2 years. There were four primary indications because of inability to use the abdominal aorta, and 23 secondary indications for late failure of a previous lower limb revascularisation: two aorto-prosthetic false aneurysms, nine infected aorto-bifemoral bypasses and 12 occluded grafts. Three deaths and one paraplegia occurred during the postoperative period, and three prosthetic occlusions and one popliteal embolism were successfully treated. During follow up (6-72 months) five deaths and three graft occlusions were observed; at 5 years, the cumulative life expectancy was 61.8 +/- 26.8%, and the cumulative secondary graft patency was 72.6 +/- 24.7%. One prosthetic infection and one ureteric fistula occurred and both were successfully treated. Thoracic aorta to femoral artery bypass is a simple extra-anatomic technique which can be used in cases of failure of a previous aorta to lower limb reconstruction. The haemodynamic results are good, and late results are better than axillo-femoral or bifemoral bypass. PMID- 1592130 TI - Outcome of progression from carotid stenosis to occlusion. AB - The incidence of symptoms at the moment the internal carotid artery (ICA) occludes was assessed in 33 patients. Duplex scanning was performed to determine the progression from stenosis to ICA occlusion. There were 24 patients with a primary stenosis and nine with a restenosis after a carotid endarterectomy. In 18% (6/33) the occlusion was accompanied by a stroke. A transient ischaemic attack (TIA) was seen in 12% (4/33) of patients and 70% (23/33) remained asymptomatic. There was no difference in stroke rate between patients with primary stenosis (4/24:17%) and those with restenosis (2/9:22%). The mean follow up was 3.2 years and the mean elapse time to occlusion in patients with a stroke was 20 months, with a TIA, 32 months, and in asymptomatic patients, 44 months. It was also shown that a stenosis of greater than 80% diameter reduction had a faster progression (mean 1 year) than a less than 80% stenosis (mean 3.5 years) (p = 0.04). Patients with a stenosis greater than 80% tended to have a higher incidence (40%:2/5) of stroke at the time of occlusion than patients with a stenosis less than 80% (14%:2/28). The results show that an occlusion of the ICA is accompanied by a stroke in 18% of the cases and that patients with a rapid progression and/or greater than 80% stenosis are at high risk. From this point of view a carotid endarterectomy should be considered in order to prevent an occlusion of the ICA and a high risk of stroke. PMID- 1592131 TI - Microvascular reactivity differences between the two legs of patients with unilateral lower limb ischaemia. AB - Posturally induced microvascular constriction in the skin of the leg is disturbed in severe ischaemia. It is unknown whether this disturbance is of local or central origin and whether the stage of ischaemia at which this disturbance occurs differs when the nutritive and thermoregulatory flow levels are compared. We investigated the effect of posture on the skin microcirculation in 21 patients with unilateral severe ischaemia. The results were compared with those from the contralateral, asymptomatic leg and with results from 11 age-matched controls. Patients were investigated in supine and sitting positions, using capillary microscopy to measure nutritive flow, and laser Doppler fluxmetry (LDF) to measure thermoregulatory flow, of the big toes. In the supine position, capillary flow and LDF were lower in the diseased than in the asymptomatic and control legs. After changing from the supine to the sitting position, capillary perfusion decreased in all three groups, but was most pronounced in the controls. Laser Doppler flux decreased in the controls, but increased in the diseased legs, suggesting disturbed vasoconstriction mechanisms in the deeper skin microvessels. These findings indicate that in severe limb ischaemia, posturally induced microvascular reactivity is sustained at the nutritive level but not at the thermoregulatory level. This disturbed reactivity is considered a local phenomenon, as it is not observed in the contralateral leg. PMID- 1592132 TI - The role of colour flow duplex screening in infra-inguinal vein grafts. AB - To assess the indications for routine colour flow duplex surveillance, 43 infra inguinal autogenous vein grafts were prospectively entered into a surveillance protocol. Screening consisted of measurements of ankle brachial indices (ABIs) and colour flow duplex imaging of the entire graft length. Twelve significant stenoses have been detected in 10 grafts (23%) using duplex, all within 6 months of surgery. All grafts at risk had arteriography confirming the duplex findings, but detecting one additional stenosis. Two grafts at risk were not detected by duplex scanning (sensitivity 83%). All grafts at risk (12) had a serial fall in resting ABI of more than 0.1. Most of the detected graft stenoses could be corrected surgically, improving the 1 year primary cumulative patency rate of 54% to a secondary patency rate of 88%. This study suggests that resting ABI measurements are a very sensitive (sensitivity: 100%) and simple primary screening procedure, provided that all grafts with ABI changes of more than 0.1 are further evaluated. The interval specificities of ABI measurements were 77% at 3, 71% at 6, 67% at 12 and 78% at 18 months (mean 73%). About 60% of ABI-screened grafts needed further evaluation because of ABI changes of greater than 0.1, incompressibility of arteries (ABI greater than 1.3) or extension of the graft to the ankle or pedal arteries. Colour flow duplex scanning was very useful in excluding or identifying and localising graft problems and deciding on further invasive diagnostic and therapeutic procedures. Ankle brachial index measurements as the primary examination for selecting patients for colour flow duplex scanning seems to be a safe screening procedure. PMID- 1592134 TI - Alanine uptake by the endothelium of canine blood vessels and by the vessels of human umbilical cord. AB - In order to determine whether the endothelium of vascular wall fragments possesses an active uptake mechanism for alanine identical to the one present in endothelial cells in tissue culture samples of canine aorta, carotid artery and vena cava, human umbilical cord vessels, were incubated in vitro in the presence of labelled alanine. In a series of experiments, it was observed that all the tissues investigated accumulated a significant amount of this substrate against a concentration gradient, and that the accumulation was saturable in the presence of sodium. This uptake was sodium-dependent, was significantly inhibited by ouabain and was greatly reduced under anoxic conditions. Finally, the uptake was completely abolished by prior mechanical or osmotic destruction of the intima. In conclusion, the very reproducible measurement of active alanine uptake in fragments of blood vessels may be a valuable method of evaluating the integrity of the endothelium. PMID- 1592133 TI - High aortic occlusion associated with lupus anti-coagulant. AB - Lupus anti-coagulant (LAC) has been recognised in association with venous and arterial thrombotic events. We retrospectively investigated the relationship between LAC and 21 patients with juxtarenal high aortic occlusion. Four of the 21 patients were LAC positive (19%), one of whom was a woman suffering from systemic lupus erythematosus (SLE). The three men had neither SLE nor any other connective tissue disease. The mean age of the four patients was 43.5 years and three of them (75%) were younger than 50 years of age. By contrast, the mean age of the 17 patients without LAC was 59.9 years and 14 of them (82.4%) were older than 50 years. The postoperative courses in all four patients with LAC undergoing arterial reconstructions were uneventful. Two patients were treated by either anti-coagulation or anti-platelet agents, postoperatively. The present paper demonstrates for the first time that, in patients with juxtarenal high aortic occlusion, the incidence of LAC positivity is higher in younger patients (below 50) than in older patients (above 50). In addition, our results show that a preoperative evaluation of the presence of LAC is required in cases with juxtarenal high aortic occlusion, particularly when the partial thromboplastin time (PTT) is prolonged and the patients are younger than 50 years old. PMID- 1592135 TI - The combination of liquid crystal thermography and duplex scanning in the diagnosis of deep vein thrombosis. AB - One hundred patients with clinically suspected deep vein thrombosis (DVT) were studied by liquid crystal thermography (LCT), duplex scanning and venography. Liquid crystal thermography was found to have a negative predictive value of 97% if performed within 1 week of the onset of symptoms. Duplex scanning had a sensitivity of 93% and specificity of 91% for all thrombi (proximal and calf). On the basis of these results a plan of investigation has been formulated that would avoid duplex scanning and venography in 39 of the 100 patients. Duplex scanning alone would be appropriate in 56 of the remaining 61 patients. Only six patients would be unsuitable for duplex scanning because of a very tense tender leg and require venography. The plan would miss one calf thrombus and result in treating three patients unnecessarily. This policy would be not only effective but also cost-effective. PMID- 1592136 TI - The fate of bilateral lower limb amputees in end-stage vascular disease. AB - Sixty-six patients with end-stage peripheral vascular disease who had undergone bilateral major amputation of the lower extremities in our institution during the 10-year period January 1980-December 1989 were reviewed. There were 46 males and 20 females with an age range from 34 to 91 years (mean 67.7 years). A 98.5% follow-up was achieved. Of these patients 25% underwent their second amputation in the first, 50% within the second and 75% within the third postoperative year, notwithstanding the fact that prior attempts at revascularisation had been performed in 62% of all patients. The 30-day hospital mortality was 4.5%. The initial level of amputation was metatarsal in 14.4%, below knee in 66.6%, through knee in 9.9% and above knee in 9.1%. Out of a total of 132 stumps 89 healed by primary intention. Following secondary revisions and amputations the final level of amputation was metatarsal in 7%, below knee in 49%, through knee in 14% and above knee in 30%. Survival rates were 62% after 2 years, 31% after 5 years, and 14% after 8 years. By this time all diabetics had died, while 33% of non diabetics were still alive (p greater than 0.02). Age, sex and amputation level had no bearing upon survival rate. Forty-three patients (65.1%) were ambulatory after their first amputation, but following contralateral amputation barely more than half (23 patients) were able to walk. In the presence of bilateral stage IV disease it is highly important to rehabilitate the patient immediately following unilateral amputation before considering amputation of the contralateral limb, otherwise the patient will not become ambulatory. PMID- 1592137 TI - Mycotic aneurysm of the cervical carotid artery due to Salmonella enteritidis. AB - A case of mycotic carotid aneurysm due to Salmonella enteritidis infection is reported. The features of the condition and the principles of treatment are described. PMID- 1592138 TI - Rupture of embolised coeliac artery pseudoaneurysm into the stomach: is coil embolisation an effective treatment for coeliac anastomotic pseudoaneurysm? AB - An elderly woman with an anastomotic pseudoaneurysm of the coeliac artery, after previous treatment of a thoraco-abdominal aortic aneurysm, was treated by stainless steel coil embolisation. One year later, the embolised pseudoaneurysm ruptured into the stomach and total gastrectomy and aneurysmorraphy was necessary. She is leading a normal life 6 months later. PMID- 1592139 TI - Prostacyclin for intra-arterial drug injection. PMID- 1592140 TI - [A 79-year old man with hypertension, hypokalemia, hyporeninemia and hypoaldosteronemia similar to Liddle's syndrome]. AB - A 79-year old man with hypertension, hypokalemic metabolic alkallosis, hyporeninemia and hypoaldosteronemia was studied. Blood pressure fell and serum potassium returned to normal after sodium restriction and the administration of triamterene. Serum DHEA, DOC, corticosterone, 18-OH-corticosterone, 11-deoxy cortisol, cortisol were within normal range. Adrenal CT scanning did not reveal an adrenal tumor. The excretions of urinary kallikrein and prostaglandin E2 were within the normal range. Although an atrophic juxtaglomerular apparatus and arteriosclerotic change were observed by renal biopsy, there was no evidence of hypokalemic nephropathy. From these results, it is suggested that this patient has a defect in handling sodium and potassium in the distal tubules. This is similar to that observed in Liddle's syndrome. PMID- 1592141 TI - [Ultrasensitive immunoassay of hormones]. AB - Two methods for ultrasensitive immunoassay of peptide hormones are presented. One is to reduce the nonspecific binding of labeled reactants in two-site immunoassay by transfer of immune complexes containing labeled reactants from one solid phase to another. The other is a novel noncompetitive immunoassay method for small peptides, in which peptides are biotinylated and subsequently measured by two site assay using anti-peptide antibody and avidin (streptavidin). PMID- 1592142 TI - [Mini review on inhibins and activins]. AB - Recent researches on inhibin and activin were reviewed. This mini review contains brief history of researches on inhibins and activins, criteria, chemistry, the site of production of these two hormones, assay method (bio- and radioimmunoassay), changes of serum inhibin levels in normal physiologic states and in various pathologic states of men and women, actions of inhibins and activins upon FSH and LH secretion from the pituitary, upon other pituitary functions, upon brain functions, erythropoiesis, erythroleukemia, bone and bone marrow, immunology, other organs such as liver, pancreas, adrenals, placenta, Xenopus oocyte and general cell proliferation, paracrine and autocrine actions of these hormones inside the ovary and the testis, activin receptor, inhibin receptor, follistatin, effects of exogenous administration of recombinant inhibin and activin, and TGF-beta super gene family. PMID- 1592143 TI - [A case of panhypopituitarism with normal height manifesting the transection of the pituitary stalk and the formation of the ectopic and eutopic posterior lobes]. AB - A 33-year-old man with hypopituitarism is documented. He was born at breech presentation without asphyxia. He was the shortest in his class throughout his school days. He kept slowly growing and reached 172.8 cm at the age of 33. He was devoid of secondary sexual characteristics. Endocrinological studies showed panhypopituitarism with elevated levels of plasma TSH (15.0 microU/ml). TRH administration resulted in a marked increase in plasma TSH. Posterior pituitary function was normal. MR imaging showed transection of the pituitary stalk and the presence of ectopic and eutopic posterior lobes. The replacement of corticosteroid was initiated, and exaggerated response of TSH to TRH disappeared. Delayed bone maturation due to hypogonadism and hypothyroidism was one of the reasons why he had normal height without GH therapy. The significance of his peculiar MRI findings remains to be determined. PMID- 1592144 TI - [Long-term treatment of acromegaly and gigantism with octreotide (SMS 201-995)]. AB - Twenty-one patients with active acromegaly and two patients with pituitary gigantism were treated with the long-acting somatostatin analogue octreotide (100 600 micrograms/day, sc, two or three times daily or 300-1500 micrograms daily by intermittent sc infusion) for 9-63 months. There was rapid clinical improvement. The fasting plasma GH levels were significantly suppressed (less than 50% of the values before treatment) in 17 patients and were normalized (less than 5 ng/ml) in 6 patients (27.3%). Plasma IGF-I levels were lowered by 50% and were normalized in 7 out of 18 cases. The effect of octreotide on pituitary tumor size was evaluated in 13 patients. In 4 cases, the shrinkage of the pituitary tumor was detected by computed tomographic scans and/or magnetic resonance imaging studies. The drug was generally well tolerated. However, there were probably newly formed gallstones in two patients during the therapy. Our study suggests that octreotide is an effective and relatively safe new approach for treating active acromegaly and gigantism. PMID- 1592145 TI - X-linked hypophosphatemia. A phenotype in search of a cause. AB - XLH is an important disease, it is the subject of several classic articles in the medical sciences (Scriver et al., 1991), and it has been an important stimulus to study renal hypophosphatemias and how they are involved in rickets and osteomalacia (Scriver, 1974; Scriver and Tenenhouse, 1991). Renal transport is the major determinant of phosphate homeostasis in mammals and it is unlikely that this important biochemical parameter would have been left by evolution to a single renal transport system. Together physiologists and geneticists found that the mammalian kidney has several gene products dedicated to phosphate transport. That has implications for biochemists in search of a membrane protein to clone and explain XLH, for example. Let us suppose the transporter affected in XLH is cloned. Will it be the product of the XLH (or Hyp or Gy) locus? One will not know until the transporter gene is mapped. There is no question of the X-chromosome locus product being protein kinase C for example, since it maps to autosomes. But where does one start in the search for the X-chromosome locus? With the elusive putative diffusible factor or with the transporter, or perhaps with an enzyme in vitamin D hormone metabolism? Which goes to say that it is necessary to know the phenotype to arrive at the right locus. Or is it? Sufficient physical mapping of region Xp22.31-p21.3 will eventually lead to positional cloning of the Hyp gene. What will it be?(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592146 TI - Glucose-sensing by the pancreatic B-cell: the mitochondrial part. PMID- 1592147 TI - Characterization of a cell-free protein synthesizing system from rat lung. AB - 1. A cell-free protein synthesizing system has been developed from a novel source, namely the rat lung. 2. The system translates endogenous mRNA at a linear rate for up to 10 min at approx 5% of the in vivo rate. 3. With the use of edeine and 7-methylguanosine-5'-triphosphate (m7GTP), specific blockers of peptide chain initiation, we have demonstrated that 40-60% of total amino acid incorporation is attributable to reinitiation on nascent polypeptide chains. 4. The lung cell-free system will be a valuable asset when investigating the mechanisms involved in the regulation of pulmonary protein synthesis. PMID- 1592148 TI - Substrate specificity of the cell envelope-located proteinase of Lactococcus lactis subsp. lactis NCDO 763. AB - 1. The specificity of the cell envelope-located proteinase of Lactococcus lactis subsp. lactis NCDO 763 towards caseins has been submitted to a statistical study. Positive and negative relations have been evidenced between several amino acids and positions P6 to P'2 of the cleaved bonds. 2. Fragment 1-23 of alpha s1 and oxidized B chain of insulin are well cleaved by the proteinase while CMP (fragment 106-169 of kappa-casein) is a poor substrate. 3. Comparison with other cell envelope-located proteinase has been done. The enzyme of the strain 763 hydrolyses alpha s1-casein and fragment 1-23 of alpha s1-casein as the enzyme of the strain Sk11 and beta-casein as the enzyme of the strain Wg2. 4. The specificity of these proteinases and the comparison of their amino acid sequences let us postulate a more complex substrate binding area for these lactococcal proteinases than for the subtilisin. PMID- 1592149 TI - Effect of glycosaminoglycans on peptide bond formation in bacterial ribosomes. AB - 1. A cell-free system derived from E. coli has been used in this study. The process of peptide bond formation was assessed with the aid of the puromycin reaction, which is catalyzed by peptidyltransferase. 2. This reaction is inhibited by heparin, in contrast, this reaction is activated by hyaluronic acid. 3. The presence of heparin decreases the percentage of formed initiation complex (complex C), but hyaluronic acid, chondroitin sulphate and keratan sulphate have no effect on the formation of complex C. 4. From other types of glycosaminoglycans, only hyaluronic acid increases the stability of active complex C. PMID- 1592150 TI - Effects of growth medium, electrical stimulation and paralysis on various enzyme activities in cultured rat muscle cells. Comparison with activities in rat muscles in vivo. AB - 1. Replacement of fetal calf serum and chicken embryo extract by Ultroser G and rat brain extract during the proliferation phase resulted in a higher maturation grade of cultured rat muscle cells after 7 days of differentiation, on base of the percentage of the muscle specific isoenzyme of creatine kinase (CK-MM). 2. Furthermore, the activities of creatine kinase, citrate synthase, cytochrome c oxidase and hexokinase were significantly higher. 3. Compared to the enzyme activities in m. quadriceps of 10 day-old rat and m. quadriceps, m. soleus and m. extensor digitorum longus of young adult rats, the metabolic capacity of cultured myotubes most closely resembles that of the first muscle. 4. Paralysis with tetrodotoxin caused a slight decrease of the creatine kinase activity and the percentage of CK-MM of cultured myotubes and an increase of the activities of hexokinase, phosphorylase and AMP deaminase. 5. Electrical stimulation performed at different frequencies and time periods had no effect on the enzyme activities of cultured rat muscle cells. 6. Only the AMP deaminase activity was decreased after intense electrical stimulation. PMID- 1592151 TI - Nuclear distribution pattern of tumour-associated nonhistone protein of mol. wt 48,000. AB - 1. As a further step toward characterizing nonhistone protein of mol. wt 48,000 which was found to be much more abundant in animal tumour cells than in normal ones [Krajewska W.M., Lipinska A., Marszatek M., Kilianska Z., Wojtkowiak Z. and Klyszejko-Stefanowicz L. Cell. Biochem. Funct. 8, 79-89 (1990)] its intranuclear localization in hamster liver and Kirkman-Robbins hepatoma was studied. The protein was identified by immunoblotting technique in the presence of antibodies against polypeptide of mol. wt about 48,000 from Kirkman-Robbins hepatoma. 2. Distribution of antigen with mol. wt of 48,000 in nuclear fractions representing different levels of nuclear material organization, i.e. in nucleoli, nuclease sensitive and nuclease-resistant fractions, and extensive nuclease digestion products separated by size on Bio-Gel A-50m; implied the structural role of this component. 3. Fractionation of endogenously digested nuclei into low salt extract, high salt extract and nuclear matrix revealed that in normal liver the antigen studied is associated with nuclear matrix while in hepatoma this component appeared in high salt extract. 4. These results suggest that polypeptide with mol. wt of 48,000 is a shuttling protein which may be involved in reorganization of nuclear matrix during neoplastic transformation. PMID- 1592152 TI - Isolation and characterization of a Vicia graminea and Vicia unijuga lectins binding (Vgu) glycoprotein with Thomsen-Friedenreich (T) activity from human liver metastases of pancreas carcinoma. AB - 1. Perchloric acid-soluble fraction from liver metastases of pancreas carcinoma of a patient with blood group B, was subjected to a systematic affinity chromatography using Vicia unijuga lectin (VUA) and Arachis hypogaea anti-T lectin (PNA) as immobilized ligands and separated into three fractions, B-active glycoprotein fraction, serologically inactive glycoprotein fraction and glycoprotein (VP) fraction exhibiting reactivities for Vicia graminea lectin (VGA), VUA and PNA. 2. VGA- and VUA-binding (Vgu) glycoprotein with Thomsen Friedenreich (T) activity which was isolated, in a high state of purity, from VP fraction by HPLC using Asahipak GS-710 column, was demonstrated to be a mannose rich glycoprotein with mol. wt of 1492 kDa and contained 40.40% carbohydrate. PMID- 1592153 TI - Synthetic oligopeptide substrates which fail to compete with H1 histone for type II and type III isoenzymes of protein kinase C. AB - 1. The oligopeptide AAASFKAKK which contains recognition motifs similar to that found in the surrounding of the site of H1 histone phosphorylated by protein kinase C is unable to compete with H1 histone for the type II and type III isoenzymes, though it is a good substrate for protein kinase C and it is able to compete with a physiological substrate of the enzyme. 2. Among several oligopeptides tested as an alternative substrate a very basic peptide proved to be the most effective inhibitor of H1 histone phosphorylation. This oligopeptide substrate contains basic recognition motifs at both sides of the phosphorylated residue at variance with the sequence of H1 histone in the surrounding of the phosphorylated site. PMID- 1592154 TI - Decreased activity of the phosphate carrier and modification of lipids in cardiac mitochondria from senescent rats. AB - 1. A comparative study of the effects of aging on the transport of phosphate and on the lipid composition in cardiac mitochondria isolated from young and aged rats was carried out. 2. Mitochondria from aged rats (26 month old) translocate phosphate much more slowly than do mitochondria from young control rats (4 month old). 3. Kinetic analysis of the phosphate transport show that only the Vmax of this process is decreased while there is no change in the Km value. 4. There is no appreciable difference in either the respiratory control ratios or in the ADP/O ratios between mitochondria from young and aged rats. 5. The heart mitochondrial lipid composition is altered in aged rats; in particular, the cholesterol/phospholipid molar ratio increases and the content of cardiolipin decreases with aging. PMID- 1592155 TI - Effect of adipose tissue site, animal size, and fasting on lipolysis in bovine adipose tissue in vitro. AB - 1. Lipolytic rates expressed as mumol glycerol released per mg protein increased with body weight in Holstein steers. 2. Lipolytic rates were greatest in both inner and outer back fat and lowest in omental, perirenal, and intermuscular fat depots. 3. Epinephrine stimulated overall glycerol release 3-5-fold. 4. Fasting resulted in greater basal lipolytic rates but epinephrine-stimulated rates tended to be greater for nonfasted steer adipose tissue. 5. Lipolytic activity in adipose tissue seems to increase with growth and fattening, and differences in lipolytic rates between various depots diminish with growth. PMID- 1592156 TI - Ferric(III) ions inhibits copper(II)/hydrogen peroxide-catalyzing lipid peroxidation in human erythrocyte membranes. AB - 1. Effect of ferric ions (Fe3+) on the lipid peroxidation catalyzed by copper ions (Cu2+) and hydrogen peroxide (H2O2) was studied in human erythrocyte membranes. 2. The formation of thiobarbituric acid-reactive products elicited by CuCl2/H2O2 was inhibited by FeCl3 in a concentration-dependent manner; 0.25 mM FeCl3 were enough to cause 50% inhibition of the formation of peroxides. 3. The inhibitory effect of FeCl3 is not due to competition against Cu2+. 4. FeCl3 inhibited the initiation, but did not inhibit the propagation of Cu2+/H2O2 catalyzing lipid peroxidation. 5. In the heat- or trypsin-treated erythrocyte membranes, FeCl3 had no inhibitory effect on Cu2+/H2O2-catalyzing lipid peroxidation. 6. Sodium azide, an inhibitor of catalase, had no effect on the inhibitory effect of FeCl3. 7. These results suggest that a protein factor(s), which is not catalase, is involved in the inhibition of Cu2+/H2O2-catalyzing lipid peroxidation by Fe3+. PMID- 1592157 TI - Iron transfer from urate-Fe(III) to citrate and ATP. AB - 1. Urate, citrate and ATP, which form stable complexes with ferric ions, are proposed to function as low mol. wt iron binding agents in humans. 2. Citrate and ATP were found to readily take up iron from the urate-Fe(III) complex; the study suggests that citrate and ATP may be physiologically more important iron binding agents than urate. PMID- 1592158 TI - Fasting induced alterations in mitochondrial palmitoyl-CoA metabolism may inhibit adipocyte pyruvate dehydrogenase activity. AB - 1. Adipocytes from fed and fasted (24 hr) groups of rats were fractionated into mitochondria, microsomes and plasma membranes. 2. Fasting significantly decreased the mitochondrial activity of palmitoyl-CoA synthetase, palmitoyl-CoA hydrolase, beta-oxidation and pyruvate dehydrogenase. 3. Fasting elevated intramitochondrial long-chain acyl-CoA. 4. Pyruvate dehydrogenase was inhibited 50% by addition of 30 microM palmitoyl-CoA. 5. Fasting-induced changes in palmitoyl-CoA metabolism may modulate pyruvate dehydrogenase activity in adipocyte mitochondria. PMID- 1592159 TI - Characterization of bovine liver cytosolic 3 alpha-hydroxysteroid dehydrogenase and its aldo-keto reductase activity. AB - 1. 3 alpha-Hydroxysteroid dehydrogenase was purified to homogeneity from bovine cytosolic fraction, which was monomeric and its molecular weight was estimated to be about 35 kDa. 2. The enzyme had ability to catalyze NADP(H)-dependent oxidoreduction of position 3 alpha-hydroxy and keto group of steroids and also could catalyze the reduction of some ketones and quinones. 3. In addition, benzenedihydrodiol was one of the substrates of dehydrogenase activity with NADP+. 4. Indomethacin, synthetic steroids and SH-reagents were potent inhibitors for this enzyme. 5. Inactivation of the enzyme by GSSG-treatment was restored to its original activity by the addition of DTT. 6. The presence of coenzyme, 0.33 mM NADP+, completely protected from the DTNB-inactivation. 7. Bovine liver cytosolic enzyme immunologically crossreacted with rat liver 3 alpha hydroxysteroid dehydrogenase. PMID- 1592160 TI - Transfer of N-acetylglucosamine to nuclear endogenous acceptors of rat hepatocytes. AB - 1. Nuclei were prepared from rat hepatocytes. A biochemical analysis of marker enzymes showed that the nuclei are not contaminated by other subcellular fractions, especially endoplasmic reticulum. 2. The transfer of [14C]N acetylglucosamine to endogenous acceptors were studied comparatively in the nuclei and in the other subcellular fractions of rat hepatocytes. 3. In this report we describe the presence of the transfer of N-acetylglucosamine within the nucleus of rat hepatocytes. We found 21% of this transfer in the nucleus fraction with an enrichment of 26 in comparison to homogenate. PMID- 1592162 TI - The effective use of differential scanning calorimetry in the optimisation of freeze-drying processes and formulations. AB - The formulation and processing variables required for the effective freeze-drying of labile biologicals can be determined from an understanding of the physics of freeze-concentration. Three measurable values, Tg' (the glass temperature associated with maximum freeze-concentration), Wg' (the unfrozen water at this temperature) and Tg (the glass temperature of the dried product) are the keystones. These can be obtained by differential scanning calorimetry. This paper describes their measurement. Techniques to increase the detectability of glass transitions are discussed. Method of calculating Wg' from DSC power-time curves are critically reviewed. An example is presented in which it is demonstrated how failure to perform primary drying below the glass transition results in products on inferior quality. Finally, it is described how measurements of the glass temperature of the "dry" product can be used to predict storage stability. The limitation of using moisture determination to predict stability is high-lighted. PMID- 1592161 TI - The insulin signal and its effects on the pyruvate dehydrogenase complex in circulating lymphocytes of obese children. AB - 1. Studies have shown that in circulating lymphocytes pyruvate dehydrogenase (PDH) is responsive to insulin. 2. To improve existing knowledge on how insulin influences PDH behaviour, situations in which cell responsiveness to insulin is impaired could be of interest. 3. PDH behaviour in circulating lymphocytes from obese children, with high plasma insulin levels and normal glucose tolerance, was examined. 4. Masking and unmasking processes of insulin receptors on the plasma membrane appear to modulate the enzyme response to insulin. PMID- 1592163 TI - Measurements of temperatures, ice evaporation rates and residual moisture contents in freeze-drying. AB - The temperature measurements during freezing and freeze-drying are described, and the results obtained using thermocouples and resistance elements (Pt 100) are compared with the barometric temperature measurements (BTM). The BTM is checked with a mass spectrometer, thermoelectric instruments and an absolute capacity measuring gauge. The temperature measurements are also shown as a function of the location of the sensors in the product. The evaporating rates of ice are given as a function of operating pressure. It is shown that the residual moisture content is a function of the temperature of each product. The equilibrium vapour pressure as a function of temperature is shown as desorption isotherms. Therefore, the residual moisture content can be determined by measuring this equilibrium vapour pressure (or at least a pressure very close to the equilibrium vapour pressure). PMID- 1592164 TI - Methodology for in-process determination of residual water in freeze-dried products. AB - The integrity of freeze-dried biological products after reconstitution, as well as their stability during storage, is often more sensitive to small variations in residual moisture level than traditional low molecular weight drugs. Susceptibility to over-drying has also been documented for biological products. This places additional demands on the quality of in-process monitoring to achieve the desired level of residual water. This discussion is a critical overview of methodology for in-process moisture determination, including product temperature measurement, comparative pressure measurement, pressure rise, and residual gas analysis. Advantages and limitations of these methods are discussed. PMID- 1592165 TI - Measurement of final container residual moisture in freeze-dried biological products. AB - The Center for Biologics Evaluation and Research has changed its regulations pertaining to residual moisture in freeze-dried biological products as published in Title 21 of the Code of Federal Regulations for Food and Drugs. The new regulation requires that each lot of dried product be tested for residual moisture and meet and not exceed established limits as specified by an approved method on file in the product license application. The gravimetric or loss-on drying method is no longer listed as the required method; the 1.0% moisture limit is no longer specifically stated in the regulation. These revisions were made to bring the regulation into line with changes in residual moisture testing methods and the results obtained when new testing methods were applied to the determination of residual moisture. This is illustrated with data for Measles Virus Vaccine Live and Haemophilus b Polysaccharide Vaccine using final container residual moisture test results obtained by the gravimetric, coulometric Karl Fischer, thermogravimetric and thermogravimetric/mass spectrometric methods. Guidelines for the determination of residual moisture in dried biological products have been issued to describe residual moisture test methods and procedures used to set product residual moisture limits. For most products levels of residual moisture should be low, usually from less than 1.0% to 3.0%, so that the viability, immunologic potency and therefore the stability of the product is not compromised over time. PMID- 1592166 TI - Moisture transfer from stopper to product and resulting stability implications. AB - Since the stability of a freeze-dried product is often sensitive to the level of moisture, control of residual moisture by attention to the secondary drying phase of the freeze-drying process is of considerable importance. However, several reports in the literature as well as our own experience suggest that low residual moisture immediately after manufacture does not ensure low moisture throughout the shelf life of the product. Equilibration of the product with moisture in the stopper can lead to significant increases in product water content. This research is a study of the kinetic and equilibrium aspects of moisture transfer from stopper to product at 5 degrees C, 25 degrees C, and 40 degrees C for two amorphous materials: vancomycin (highly hygroscopic) and lactose (moderately hygroscopic). Stoppers are 13 mm butyl rubber (#1816, West Co.) slotted freeze drying stoppers which were studied: (a) "U"-with no treatment; (b) "SV1"-steam sterilized followed by 1 hr vacuum drying; and (c) "SV8"-steam sterilized followed by 8 hrs vacuum drying. No evidence was found for moisture transmission through the stopper. Rather, the product moisture content increases with time and reaches an apparent equilibrium value characteristic of the product, amount of product, and stopper treatment method ("SV1" much greater than "U" greater than "SV1"). As a first approximation, the rate of approach to "equilibrium" depends only on temperature (t1/2 approximately 10 months at 5 degrees C to approximately 4 days at 40 degrees C) with the "equilibrium" water content being independent of temperature. The "equilibrium" moisture content increases as the dose decreases and is larger for vancomycin than for lactose. The "equilibrium" moisture contents range from 5.0% (25 mg vancomycin, "SV1" stoppers) to 0.68% (100 mg lactose, "SV8" stoppers). PMID- 1592167 TI - Quality control issues in the analysis of lyophilized proteins. AB - The assessment of protein stability requires the use of many sophisticated analytical techniques. Lyophilization procedures, commonly used to improve the stability profile of protein products, may potentiate undesirable protein degradation. The potential effects of lyophilization on proteins may include denaturation, decreased potency, aggregation, oxidation, and deamidation. Methods such as high-performance size-exclusion chromatography (HPSEC), peptide mapping, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), and high performance ion-exchange chromatography (HPIEC) may be used to evaluate these effects as well as to predict the long-term stability of the product. Typical degradation mechanisms of protein products and examples of the methods used for their analysis are described. In addition, methods for monitoring residual moisture levels in lyophilized proteins are presented with emphasis on their relative advantages and disadvantages. PMID- 1592168 TI - Scanning electron microscopy of freeze-dried preparations: relationship of morphology to freeze-drying parameters. AB - The structure of the freeze-dried plug of several biological preparations was examined using scanning electron microscopy (SEM). A variety of carbohydrate preparations were frozen at two different cooling rates of 150 degrees C per minute and 1 degree C per minute. After lyophilization, residual moisture analysis demonstrated that under conditions of rapid freezing a drier product could be obtained. SEM observations showed the lyophilised plug structure of rapidly frozen material consisted of a fine amorphous meshwork, while material frozen slowly consisted of a leafy amorphous material. Freeze-dried mannitol preparations were shown to be of a crystalline nature. In most instances, rapidly frozen material was easier to reconstitute after lyophilization. SEM of proteinaceous preparations which had been frozen at differing rates also showed a variety of different appearances which were probably related to the direction of ice growth. During ice growth formation the migration of buffers and salts towards the surface may occur. Localised high salt/buffer areas may cause deterioration of the product and reduce shelf life. SEM observations were made on the freeze-dried plug of preparations which had collapsed during the lyophilization process. Typically, the basal region of the plug had a more solid structure than the open meshwork of successfully dried material. PMID- 1592169 TI - WHO guidelines for the preparation of international standards and other reference materials for biological substances. PMID- 1592170 TI - The effects of stopper drying on moisture levels of Haemophilus influenzae conjugate vaccine. AB - The discovery and development of increasingly potent biological and pharmaceutical products have resulted in very small amounts of the active ingredient in final product formulations. Pediatric vaccines with sub-milliliter dose sizes pose unique problems for final formulation and lyophilization, especially when stabilizers used are present in small amounts or are hygroscopic. Lyophilized Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PedvaxHIB) has a plug weight of about 3 mg in its final formulation. Microgram amounts of water absorbed by the lyophilized plug can cause drastic changes in the moisture content of the product. In a small percentage of the final containers absorption of moisture by the vaccine may cause aesthetic defects (plug collapse) over time, or at elevated temperatures. This paper describes drying methods developed to control residual moisture levels in stoppers used as final container closures. Results on the moisture stability of the product capped with dried and non-dried stoppers are presented. PMID- 1592171 TI - Formulation and stability of freeze-dried proteins: effects of moisture and oxygen on the stability of freeze-dried formulations of human growth hormone. AB - This research presents the results of a series of stability studies on freeze dried formulations of human growth hormone (hGH). Chemical decomposition via methionine oxidation and asparagine deamidation as well as irreversible aggregation are characterized by HPLC. Water sorption isotherms, DSC thermograms, and pulsed proton NMR data are also obtained. No glass transition temperatures are observed in the temperature range of the stability studies. The pulsed NMR data suggest onset of greater mobility in the solid at a water content slightly higher than BET "monolayer" level. Stability of freeze-dried solids at 25 degrees C and 40 degrees C is studied as a function of residual moisture and exposure to oxygen. Formulations with and without a glycine/mannitol excipient system are studied. Significant levels of chemical decomposition and irreversible aggregation occur under most conditions with the effects of residual water content and "headspace oxygen" strongly dependent on the formulation. At low water content with minimal oxygen in the vial headspace, the glycine/mannitol formulation yields optimum stability. However, for either high water content or high oxygen content in the vial, stability of hGH without excipients is superior. The qualitative effect of residual moisture on stability depends on the temperature of the stability study. Generally, the stability of a sample adjusted to a given water content by desorption (during freeze-drying) is identical to the stability of a sample prepared by sorption of water on to a previously highly dried sample. PMID- 1592172 TI - Techniques used to freeze-dry "small doses" of thrombin. AB - In can be difficult to maintain the moisture level of small quantities of freeze dried product contained in vials. We have observed that over a period of time a gradual increase in the residual moisture level in Thrombin vials containing small quantities of the freeze-dried product can sometimes be seen. No change in Thrombin potency has been observed. Investigations into the cause and resolution of this situation resulted in (1) modification of the freeze-drying cycle for vials containing small quantities of Thrombin and (2) incorporation of a special drying cycle for vial stoppers. PMID- 1592173 TI - Interactions of stabilizing additives with proteins during freeze-thawing and freeze-drying. AB - A wide variety of compounds, including sugars, polyols, amino acids and certain salts, are effective at minimizing protein denaturation during freeze-thawing. In this review we provide evidence that the mechanistic basis for this cryoprotection appears to be the same as that described by Timasheff for solute induced stabilization in aqueous solution. Namely, the stabilizers are preferentially excluded from the surface of the protein, and this interaction makes it thermodynamically unfavourable for proteins to unfold. In contrast, carbohydrate-induced preservation of labile enzymes during freeze-drying is a fundamentally different process. Using Fourier transform intra-red spectroscopy we have found that hydrogen bonding between the carbohydrate and the dried protein is required for stabilization. Thus, it appears that certain carbohydrates protect dried enzymes because these solutes serve as water substitutes for the dried protein, by satisfying the hydrogen bonding requirement of polar groups on the protein's surface. Finally, we discuss some intriguing findings on the synergistic stabilization of proteins by mixtures of divalent cations and organic solutes, which are yet to be explained. PMID- 1592174 TI - The behavior of hydration water of protein with the protectant in the view of 1HNMR. AB - The alterations of the amount of hydration water and the extent of the interaction with hydration water and protein during freezing and after freeze drying were investigated with or without cryoprotectant using 1HNMR and other methods. Ovalbumin was used as a representative protein that was stable against freezing and drying. Myosin was also used as a typical unstable protein. It was found that myosin had no stable hydration layer compared with ovalbumin. It was considered that this difference might be the major cause of the difference in the stability of both proteins against freezing and drying. With cryoprotectant, the amount of hydration water was decreased and the extent of the interaction of hydration water with protein was increased. The results suggested the effective protectant substituted for part of the hydration water and strengthened the interaction during freezing and drying. It is also possible that the formation of a "quasi-hydration layer" might protect protein against denaturation due to freezing and drying. PMID- 1592175 TI - Determining the optimum residual moisture in lyophilized protein pharmaceuticals. AB - A general concern in the lyophilization of protein pharmaceuticals is how dry a product should be in order to maintain its stability during storage. This paper presents our exploratory studies on determining if there is an optimal residual moisture content for lyophilized recombinant protein products. The proteins used in this study were methionyl human growth hormone (met-hGH) and tissue type plasminogen activator (tPA). The amount of water adsorbed on each protein can be determined and approximated as a monolayer by the Brunauer-Emmett-Teller method. The result was in good agreement with the theoretical value calculated from the total number of strong polar groups in the molecule without regard to the conformation of the protein. This approach suggests that each protein may have a minimum moisture content that is necessary to shield the polar groups, and that over-drying will lead to exposure of these groups. The effect of residual moisture content on the stability of tPA in lyophilized excipient-free powder was studied. Samples that were dried to a water content below the calculated monolayer exhibited opalescence upon reconstitution, while those that were dried to either monolayer or multilayer water content tended to show a greater loss in biological stability upon storage under temperature stress conditions. The results of our studies reveal that the generally accepted concept "the drier the better" may not be appropriate for tPA. An optimum residual moisture content is required to balance the physical stability and the biological stability. These observations may apply to other protein products as well. PMID- 1592176 TI - Effect of formulation and freeze-drying on the long-term stability of rDNA derived cytokines. AB - Lyophilized recombinant DNA-derived cytokine preparations intended for use as International Reference Material have been processed in such a way as to give batches of preparations which possess homogeneity and high stability, in order that each cytokine standard has a reasonable use of some 10 to 20 years. This has been achieved by exercising careful control at every stage of the lyophilization process. All cytokines were ampouled in microgram quantities with relatively large quantities (milligrams) of bulking agent such as albumin and carbohydrate which were shown to have no effect on the biological activity of the cytokine. Residual moisture present in the preparations and their uptake was measured by Karl-Fischer titration and found to vary from 0.5% to 4% moisture. On storage over phosphorus pentoxide these values were reduced to 0.1% to 0.5% with good reproducibility throughout the batch. Reconstitution of the freeze-dried plug was readily achieved in seconds. The stability of freeze-dried preparations of several cytokines was monitored by observing changes in biological activity after accelerated degradation studies. To date, several freeze-dried preparations have shown no loss in activity after storage at temperatures up to +56 degrees C for one year. PMID- 1592177 TI - Stabilization of dry liposomes by carbohydrates. AB - Many organisms have adopted biochemical strategies that enable them to survive dehydration, a condition known as "anhydrobiosis". In addition to resistance to the deleterious effects of drying, anhydrobiotes are also resistant to a number of other adverse environmental conditions. Studies on the biochemistry of anhydrobiotes show a strong correlation between their ability to survive drying and the production of specific sugars, of which the most widely studied is trehalose. Studies of model systems show that direct interactions of trehalose with dry biological membranes, liposomes, and isolated proteins avoid the damaging events caused by drying. Cellular components are maintained in a physical state when dry that mimics the hydrated state. Although the presence of only two disaccharides, trehalose and sucrose, has been correlated with survival of drying under natural conditions, other molecules that achieve the same results may be effective. PMID- 1592178 TI - Development of a lyophilized formulation of interleukin-2. AB - Native human interleukin-2 (IL-2) comprises a group of glycoproteins of MW 13,000 17,500. Recombinant human IL-2 (rhIL-2) (Cetus) is derived from E. coli and is not glycosylated. We have evaluated several processes for manufacturing rhIL-2, based on different chaotropic agents for solubilization of insoluble protein pastes. Formulation work carried out with material purified by one of these processes is reported here. Our studies have indicated that the presence of a stabilizer in the form of an amorphous excipient, such as amino acids, a non ionic surfactant (polysorbate 80), hydroxypropyl-beta-cyclodextrin or human serum albumin was essential for preservation of rhIL-2 during lyophilization. Each of these formulations exhibited its own unique problems. We have overcome these problems through a systematic formulation development program and have been successful in developing several lyophilized formulations of rhIL-2 with optimum properties and performance. PMID- 1592179 TI - Biological product freeze-drying and formulation. Proceedings of a symposium. Bethesda, Maryland, 24-26 October 1990. PMID- 1592180 TI - Basic aspects and future trends in the freeze-drying of pharmaceuticals. AB - Freeze-drying, as a unit operation in chemical engineering, is a complex multistage process which has to be carefully adjusted to each individual case. Its essential feature, drying from the frozen state, makes it particularly attractive for the stabilization of labile hydrated organic compounds of biological origin. However, it offers equal opportunities for the preparation of three-dimensional porous matrices for diversified physical and chemical applications. As such it is both an advanced technology for the long term preservation of unstable material and a refined operation for the development of new structures. Since freeze-drying, also called lyophilization, has been known for almost a century, and has given rise to numerous publications, this paper will not attempt to give a comprehensive review of its evolution but will focus on some of its basic requirements and potential trends. PMID- 1592181 TI - Freeze-drying and quality evaluation of protein drugs. AB - Gamma interferon from genetic recombination (IFN) has been found to have an optimal pH at about 7. An increase in IFN concentration may cause a decrease in solution clarity. A proper selection of isotonizing agent, as well as the addition of sugars, is effective in improving the clarity. The amount of IFN adsorbed on filter membranes varies with the membrane materials: cellulose acetate adsorbs much IFN, 2-fluorovinylidene is the next, followed by polysulfon, and polycarbonate adsorbs it least of all materials tested. Stainless steel adsorbs little IFN, and the level can be lowered even more by electropolishing. Silicone coating can decrease the amount adsorbed to about 1 microgram per vial of 10 ml. The effect of pressure given to the IFN solution during filtration is negligible. Transfer of IFN solution through pipings of conventional shape may result in partial deactivation by bubbling. At around pH 7, a lower pH of IFN solution causes a higher moisture level of the freeze-dried product. Moisture levels up to 3% have no effect on IFN stability. Upon reconstitution of freeze dried IFN by vigorous shaking with distilled water, filtration of the solution may become difficult because polymers might have been formed during vigorous shaking. The addition of L-cysteine, maltose, and human serum albumin, has been found to be as effective in preventing such unfavorable reactions. Fatty acids in human serum albumin, which is effective in stabilizing IFN, has been found to participate in preventing denaturation of human serum albumin upon freezing and freeze-drying; however, the denaturation prevention mechanisms are not clear yet. PMID- 1592182 TI - The effects of formulation and moisture on the stability of a freeze-dried monoclonal antibody-vinca conjugate: a test of the WLF glass transition theory. AB - Deacetylvinblastine (DAVLB) hydrazide, a cytotoxic vinca alkaloid, has been linked to the monoclonal antibody, KS1/4, via aldehyde residues of the oxidized carbohydrate groups on the antibody. The resulting KS1/4-DAVLB hydrazide conjugate is unstable in solution with both the acyl hydrazone linkage and the vinca moiety being subject to significant degradation, even at 5 degrees C. This necessitated the development of a freeze-dried formulation of the antibody-drug conjugate. Formulation factors considered were pH, ionic strength, buffer, excipient types, and excipient ratios. A formulation with equal weight ratios of mannitol, glycine, and conjugate in a low ionic strength phosphate buffer at near neutral pH was selected. Stability was studied at various moisture levels (1.4%, 3.0%, and 4.7%) and temperatures (5 degrees C, 25 degrees C, and 40 degrees C). Degradation was measured by size exclusion HPLC (aggregate formation) and by reverse phase HPLC (hydrolysis of hydrazone linkage and vinca decomposition). Differential scanning calorimetry (DSC) indicated that all samples were above their glass transition temperatures, Tg, when stored at 40 degrees C. When stored at 25 degrees C, only the highest moisture sample was initially above its Tg. However, due to crystallization of the excipients during storage and the resulting decrease in Tg, samples stored at 25 degrees C were also above their Tg during much of the storage period. The degradation rate, R, increased sharply with increasing temperature and with increasing moisture level. Degradation kinetics obeyed the Williams-Landel-Ferry relationship, R/Rg = exp[k(T-Tg)], where Rg is the degradation rate at Tg. For all three moisture levels and all three degradation pathways, k = 0.143. PMID- 1592183 TI - Lyophilization cycle development for interleukin-2. AB - The effects of temperature and pressure variation on the lyophilization of interleukin-2 (IL-2) were studied. The human recombinant IL-2 used in this study was synthesized in and purified from E. coli, formulated, and then submitted to experimental lyophilization procedures. The collapse temperature of the formulation was first determined to be -25 degrees C by differential scanning calorimetry. The effects of chamber pressure and shelf temperature on IL-2 during lyophilization were evaluated. Lyophilization chamber pressures were varied from 100 mu to 300 mu in combination with the different chamber pressures. Lyophilized cake quality was assessed by evaluating three of its properties: residual moisture, by the Karl Fischer method; the monomeric content of the protein, by RP HPLC; and oligomeric content, by SDS-PAGE. Process uniformity was checked by determining residual moisture in cakes collected from various locations in the chamber. The experimental data show that IL-2 can be lyophilized in a pilot unit within 30 hours. The IL-2 lyophilized at various primary drying conditions retained its purity and potency throughout the stability study period (12 months). PMID- 1592184 TI - The structure and properties of liquid water: recent theoretical advances. AB - Computer simulations of water, and of water in the neighborhood of biological materials, are now commonplace. However, from the molecular physicist's viewpoint existing models of water/water, water/solute, and water/substrate interactions are incorrect and potentially misleading. Almost all existing simulations of biological interest assume that the molecules are rigid, or at least that the bonds do not vibrate. In this paper we review recent advances in the theory of water interactions, emphasizing the need to construct potential energy surfaces that include vibrational degrees of freedom. PMID- 1592185 TI - The structure of water in protein crystals. AB - Protein crystals grown from aqueous media invariably contain substantial amounts of the crystallizing solution, and the structure of the protein molecules and surrounding solvent can be determined from X-ray diffraction data. Electron density maps of crystalline proteins based on such data show networks of water peaks in the solvent space within approximately 6A of the protein surface. In general, the peaks are highest for water molecules within hydrogen bonding distance of acceptor or donor atoms on the protein. With increasing distance from the protein, the water peaks decrease in height, and beyond approximately 6A they merge into the structureless solvent continuum, typical of most crystalline proteins. A few water sites are often found within the protein molecule. These water molecules appear to be trapped within the protein and presumably are more tightly bound than water external to the protein. PMID- 1592186 TI - Order and disorder in water structure of crystalline proteins. AB - Crystals of the hydrophobic protein, crambin (MW 4700), diffract to 0.83 A resolution at 130K. At this level of detail, nearly all the solvent molecules are ordered. Thus, this protein provides an excellent opportunity to study the order and disorder of water molecules at the protein surface. Water is important in stabilizing the folded conformation of the protein and also is necessary for enzymes to be active. In crambin, there are two types of water networks: pentagonal rings associated with the hydrophobic surface chain and chains linking the polar residues. The chain-like arrays appear to be strongly influenced by the protein surface. Study of these networks may enable us to predict the solvent shell in other proteins. The precise influence of the protein atoms on the solvent structure can be deduced by superimposing identical side chain functional groups and comparing the positions of atoms hydrogen-bonded to these reference atoms. Preliminary results with crambin indicate that there is different ordering of the solvent water molecules depending on whether the hydrogen-bonding protein molecule is greater than NH or greater than C = 0. Around -OH groups, the geometry of hydrogen-bonding is even more diverse. Two disordered water oxygen networks are located in each of the four major solvent regions of the crystal. Each alternate network may represent the necessity of water to pack against an irregular surface and still maximize hydrogen bonding. In the context of nature's balance between making strong bonds and maximizing disorder, the presence of disorder in the solvent structure of crambin is not unexpected. Free energy is the sum of bond energy (enthalpy) and disorder (entropy). However, considerable insight is gained from observing where disorder is and is not found in crystals of crambin. PMID- 1592187 TI - Alterations in the structure of proteins that cause their irreversible inactivation. AB - A variety of changes in environmental conditions (temperature, pH, salts, solvents, etc.) can cause protein inactivation. However, the mechanisms of irreversible protein inactivation often follow common pathways. Using heat stress as an example, the conformational and covalent processes leading to the irreversible thermo-inactivation of enzymes will be described. In particular, work in our laboratory has identified several chemical reactions which contribute to enzyme thermo-inactivation: cystine destruction, thiol-catalysed disulfide interchange, oxidation of cysteine residues, deamidation of asparagine and glutamine residues, and hydrolysis of peptide bonds at aspartic acid residues. Implications of this work for the stability of proteins during, and following, the lyophilization process will be addressed. PMID- 1592188 TI - Freeze-drying: from empiricism to predictability. The significance of glass transitions. AB - The physical and chemical principles which govern the behaviour of aqueous solutions during freezing and subsequent drying are discussed. They include undercooling, nucleation and growth of ice, the concomitant freeze concentration of the residual solution and its secondary effects, the role of water as plasticizer in amorphous organic materials, the removal of such water, and the over-riding importance of the glass/rubber transition. An understanding of the basic principles can remove most of the empiricism from freeze-drying and lead to more efficient process cycles and to products of superior quality and stability. PMID- 1592189 TI - Kinetics of a phase transition in a frozen solution. AB - The increased use of lyophilization in the preservation of biologicals, foods, and pharmaceuticals has revealed problems of discoloration, meltback, puffing, and collapse, which can result in unacceptable products. Literature reports suggest that some of these problems are related to phase transitions occurring in the frozen solutions. This paper describes the crystallization of mannitol and cefazolin sodium in frozen solution. Data were collected using calorimetric methods in both an isothermal and non-isothermal mode. Analysis of cefazolin sodium data, using the Johnson-Mehl-Avrami equation, indicated that there was a mechanism of heterogeneous nucleation of a two dimensional growth habit. Mannitol data indicated that the controlling crystallization mechanism was not constant over the temperature range studied. PMID- 1592190 TI - Vasectomy: new opportunities. PMID- 1592191 TI - Characteristics and management of feeding problems of young children with cerebral palsy. AB - The nature and extent of feeding difficulties associated with cerebral palsy was assessed in 12 infants with moderate to severe oral-motor dysfunction, compared with a control group. Data were gathered at the infants' homes by interview and by direct observation of mealtimes. The results revealed a range of long-standing problems, for which little management advice had been given. Most case infants were poorly positioned; specially designed seats were not used. The mean duration of mealtimes for case and comparison infants did not differ significantly. Case infants ate and were offered less food than the control infants. Feeding problems usually had persisted since birth and were associated with marked failure to thrive. Multidisciplinary assessments of the severe feeding difficulties of these children are indicated. PMID- 1592192 TI - Siblings and parents of children with autism: a controlled population-based study. AB - The siblings and parents of 35 children with infantile autism/autistic disorder were compared with those of children with deficits in attention, motor control and perception (DAMP) and of normal children for reported speech and language problems, reading and spelling problems, social deficits and psychiatric disorders. Children with autism tended more often to be the first and only child and there was some support for genetic stoppage in this group. Learning disorders were equally common among siblings and parents of the autism and normal groups, but less common compared with the DAMP group. Asperger syndrome was more common among first-degree relatives of children with autism compared with normal children. There was a tendency for schizo-affective disorder to be more common among mothers of children with autism. The findings are discussed in the context of a genetic model for the development of autism. PMID- 1592193 TI - The development of crawling between 18 months and four years. AB - Various quantitative and qualitative aspects of crawling were analysed in small groups of carefully selected normal toddlers of 1 1/2, two, 2 1/2, three, 3 1/2 and four years of age in a cross-sectional design. Between two and three years of age, major changes occurred in all observed aspects, resulting in differentiated, adaptive and efficient crawling. It is proposed that these changes are based on so-called adaptive variability, an age-related developmental process which seems to be a prerequisite for the development of cognition. PMID- 1592194 TI - A comparison of neurobehavioral performance of healthy term and low-risk preterm infants at term. AB - The neurobehavioral performance of a group of low-risk preterm and healthy term infants was assessed at term using the standardized Einstein Neonatal Neurobehavioral Assessment Scale. There was greater similarity than dissimilarity between the two groups; however, preterm infants demonstrated less consistent following to face and voice, and less sustained rooting and grasp reflexes. Preterm infants were more likely to have a more sustained asymmetric tonic neck reflex, a greater popliteal angle and evidence of tremor. These results support the view that processing capability appears to mature on an intrinsically programmed time- and environment-independent pathway, with environmental exposure challenging this adaptive capacity and modifying performance--predominantly with respect to reflexive elements. PMID- 1592195 TI - Non-right handedness among ELBW and term children at eight years in relation to cognitive function and school performance. AB - The relationship between handedness, neurological and cognitive deficits, and school difficulties was investigated in 114 extremely low-birthweight (ELBW) children and 145 term controls at eight years. The prevalence of non-right handedness (left and mixed) was 31 per cent for ELBW children and 19 per cent for controls. ELBW children with neurological impairments were significantly more likely to be non-right handed. No significant differences were noted between right-handed and non-right handed ELBW children and controls on tests of cognitive function, school performance and prevalence of learning difficulties. These findings suggest an association between neurological impairment and non right handedness, but do not support the hypothesis of early brain insult resulting in subtle cognitive deficits and suboptimal school performance among non-right handed ELBW children. PMID- 1592196 TI - Linguistic performance as a function of abstract task demands in children with spina bifida. AB - Children with spina bifida and hydrocephalus (SBH) have been observed to have deficits in discourse, characterized by a high frequency of irrelevant utterances and poorer performance with abstract than concrete language. The Preschool Language Assessment Instrument (PLAI) was used to compare children with SBH and language-age controls on discourse skills at four levels of abstraction. In addition, a qualitative assessment of differences in types of inadequate productions was conducted. Children with SBH performed comparably to controls on concrete levels of the PLAI, but they produced significantly more 'no response' and irrelevant responses than the controls. PMID- 1592197 TI - Evaluation of augmentation cystoplasty for severe neuropathic bladder using the hostility score. AB - In a retrospective study, the pre-operative urodynamic findings of 41 myelodysplastic patients who had undergone enterocystoplasty for intractable incontinence or deteriorating upper urinary-tracts were compared with findings from similar studies. An objective score combining five urodynamic parameters, the Hostility Score, was calculated before and after surgery to assess its clinical applicability in guiding and monitoring patient management. A score of greater than or equal to 5 should be avoided, if possible, as deleterious upper urinary-tract changes can occur even while on conservative management. In this series the mean pre-operative Hostility Score was 5.6, with 26 patients having a mean score of greater than or equal to 5. After surgery the mean score was reduced to 2.8, with no patient having a score of greater than 4. We conclude that the Hostility Score is a reliable tool for the management and follow-up of patients who have neurogenic bladder disease as a result of myelodysplasia. PMID- 1592198 TI - Neonatal tetanus: incidence and improved outcome with diazepam. AB - During a four-year prospective study at a referral hospital, 61 patients with neonatal tetanus were encountered and the contribution of continuous intravenous diazepam was noted. The over-all incidence during the study was 21.8/1000, with a mortality rate of 8.2 per cent. Signs associated with fatal outcome were hypothermia, generalized rigidity and opisthotonus. The mean dose of diazepam used was 25.8 mg/kg/day, in combination with sodium phenobarbitone (mean dose 10.7 mg/kg/day). The results suggest that high-dose intravenous (continuous) diazepam is effective, economical and feasible for reducing mortality in neonatal tetanus. Side-effects were minimal. PMID- 1592199 TI - Hemi-hydranencephaly with favourable outcome. AB - The authors report a girl with left-sided hemiparesis and unilateral hydranencephaly of the opposite side. Her psychomotor development has been far better than expected--she is only mildly delayed. Hemihydranencephaly is a rare anomaly: only five other cases are reported in the literature, three of whom were also mildly delayed. The fourth patient had multiple congenital defects combined with the hemihydranencephaly and was severely retarded, and no data on the fifth patient were provided. It may be that the prognosis for hemihydranencephaly is better than for most other destructive encephalopathies, which generally carry a poor prognosis for psychomotor development. PMID- 1592200 TI - Children with developmental dyscalculia. PMID- 1592201 TI - Economic benefits of biomedical research support. PMID- 1592202 TI - The Public Health Research Institute, New York. PMID- 1592203 TI - The ras superfamily of GTP-binding proteins: guidelines on nomenclature. PMID- 1592204 TI - Control of transcription activation by steroid hormone receptors. AB - Multiple regulatory mechanisms assure that signal transduction, involving the nuclear receptor interface, results in an accurate regulation of the respective gene networks. These mechanisms involve selective expression of the cognate receptor and its binding to specific hormone response elements of target genes. However, superimposed onto this "simple" control of activity is interpretation of the signal by the multiple functional modules of a given receptor, based on a specific interplay with 1) various factors binding to complex target gene promoters, 2) cell-specific transcription factors that mediate its enhancer function, and 3) other signaling pathways. This interpretation can be further modulated by the differential target gene specificities of receptor isoforms and, according to in vitro evidence, by factors that increase the efficiency of the receptor to interact with its response element. Thus, steroid hormone-regulated gene transcription involves a multitude of interactive elements, as is expected from the central role of nuclear receptors in homeostasis, embryonic development, and differentiation. PMID- 1592205 TI - Biochemistry and physiology of n-3 fatty acids. AB - Considering the n-3 fatty acids to be partial agonists relative to n-6 fatty acids helps consolidate into a unified interpretation the many diverse reports and controversies on the actions of these two types of essential fatty acids. Some research reports illustrate the similarities between these two types and some emphasize the differences, leaving readers to evaluate the status of n-3 fatty acids from a viewpoint that is conceptually similar to regarding a glass of water as half empty or half full. Both n-3 and n-6 types of fatty acids must be obtained through the diet because they are not synthesized de novo by vertebrates. Both types can support important physiological and developmental processes, can form eicosanoids (prostaglandins, leukotrienes, lipoxins, etc.), can be esterified to and hydrolyzed from tissue glycerolipids, and can be metabolically elongated and desaturated to a variety of highly unsaturated fatty acids. However, some nonesterified n-6 acids are vigorously converted to potent n 6 eicosanoids that exert intense agonist actions at eicosanoid receptors, whereas the n-3 acids less vigorously form n-3 eicosanoids that often produce less intense (partial) actions. Because both types owe their presence in vertebrate tissues to dietary intake, important physiological consequences follow the inadvertent selection of different average daily dietary supplies of these two types of polyunsaturated fatty acids. PMID- 1592206 TI - Endogenous retroviruses: potential etiologic agents in autoimmunity. AB - The genomes of all organisms, from yeast to humans, contain thousands of endogenous retroviruses (ERV). In most species all or almost all ERV are noninfectious, but some ERV retain open reading frames capable of encoding proteins. RNA and proteins derived from ERV are expressed in humans and other species. Until recently, there was little evidence that this ERV expression resulted in any immunologic effects. Recent studies make it increasingly clear that some ERV have important immunologic effects. The immune effects of ERV expression raise the question of a possible pathogenic role in idiopathic autoimmune diseases. Interest in this question has been heightened by the observation that some infectious retroviruses cause manifestations of autoimmunity. Nonetheless, attempts to isolate infectious retroviruses from patients with idiopathic autoimmune diseases have generally failed. The possible role of ERV in idiopathic autoimmune diseases has not yet been fully explored. This review focuses on the known and the potential immune effects of ERV, especially as they may relate to autoimmune diseases. PMID- 1592207 TI - Protein folding and protein refolding. AB - The functional three-dimensional structure of proteins is determined solely by their amino acid sequences. Protein folding occurs spontaneously beginning with the formation of local secondary structure concomitant with a compaction of the molecule. Secondary structure elements subsequently interact to form subdomains and domains stabilized by tertiary interactions. Disulfide bond formation, and cis-trans isomerization of X-Pro peptide bonds, as the rate-limiting folding reactions, are enzymatically catalyzed during protein folding in the cell. Although folding of domains is fast enough to occur cotranslationally in vivo, such vectorial folding on the ribosome is not essential for attainment of the native structure of a protein. Slow steps on the pathway to the functional protein structure are docking reactions of domains, association of subunits, or reshuffling reactions at the oligomer level. Aggregation as a competing side reaction is prevented, and the kinetic partition between competing polypeptide folding and translocation reactions is regulated by chaperone proteins binding to incompletely folded polypeptides. PMID- 1592208 TI - Immunoglobulin gene expression only in the right cells at the right time. AB - Study of immunoglobulin gene transcriptional control has disclosed a complexity that rivals that of the antibody repertoire itself. Although some DNA sequences that regulate transcription of these genes were identified almost a decade ago, additional regulatory sequences continue to be discovered, some in regions far removed (as much as 200 kb) from the actual site of transcription. This has invoked models of regulation in which the higher-order structure of chromatin must be taken into account. Within the regulatory DNA sequences themselves, there is a bewildering array of sites that bind proteins and a growing catalog of proteins that can bind each of those sites. The proteins are believed to be the physical link between the regulatory DNA sequences and the protein machinery actually carrying out transcription. Specific interactions among proteins that can bind the same site and among proteins that bind different sites have been described. A challenge remaining is to identify those interactions that occur in vivo and that lead to progressively more efficient Ig production in the developing B cell, but which disallow Ig production in non-B cells. PMID- 1592209 TI - Cytokine regulation of endothelial cell function. AB - Endothelial cells have long been viewed as a passive lining of blood vessels endowed essentially with negative properties such as that of being nonreactive to blood components. It is now evident that upon exposure to environmental signals, cytokines in particular, vascular cells undergo profound changes in gene expression and function that allow these cells to participate actively in inflammatory reactions, immunity, and thrombosis. Different mediators (e.g., interleukin-1 [IL-1] and interferon-gamma) activate relatively distinct sets of functions. These functional programs expressed in activated endothelial cells include the production by the same cells of cytokines (e.g., IL-1, IL-6, chemotactic cytokines, and colony-stimulating factors), which regulate hematopoiesis, the differentiation and proliferation of T and B lymphocytes, and the extravasation of leukocytes. The identification of cytokine circuits through which vascular cells participate to thrombotic, inflammatory, and immune reactions provides novel targets for therapeutic intervention. PMID- 1592211 TI - Antibodies against crystals. AB - We suggest that crystals, when introduced into an organism, may behave as conventional antigens, mediating the production of specific antibodies. These antibodies would bear an imprint of the crystal surface and may consequently behave as a nucleating matrix in a new crystallization event. Thus, they would behave as catalytic antibodies. We show that IgG antibodies isolated from patients suffering from gout, a joint disease caused by crystals of monosodium urate monohydrate (MSUM), accelerate the appearance of new crystals of MSUM from a supersaturated solution of the salt in vitro. The same effect is not observed for IgG antibodies isolated from the joint fluids of patients with other joint diseases, such as pseudogout, rheumatoid arthritis, or osteoarthritis. Furthermore, IgG antibodies obtained from rabbits injected subcutaneously with crystals of MSUM, were also nucleating towards MSUM crystals. PMID- 1592210 TI - Dietary fatty acid thresholds and cholesterolemia. AB - Results obtained with cebus monkeys indicate that dietary myristic (14:0) and palmitic (16:0) acids exert disparate effects on cholesterol metabolism, whereas the ability of linoleic acid (18:2) to decrease total plasma cholesterol displays an upper limit or threshold. Reanalysis of published data suggests a similar situation pertains in humans. In agreement with an earlier human study, 14:0 appears to be the principal saturated fatty acid that raises plasma cholesterol whereas 18:2 lowers it. Oleic acid (18:1) appears neutral. The effect of 16:0 may vary. In normocholesterolemic subjects consuming diets containing less than or equal to 300 mg/day of cholesterol, 16:0 appears to be without effect on plasma cholesterol. However, in hypercholesterolemic subjects (greater than 225 mg/dl) and especially those consuming diets providing cholesterol intakes of greater than or equal to 400 mg/day, dietary 16:0 may expand the plasma cholesterol pool. PMID- 1592212 TI - A fragment of metabolic prehistory. PMID- 1592213 TI - Cooking and trimming by scientific giants. PMID- 1592214 TI - To teach and to learn: past as prologue. PMID- 1592215 TI - To teach and to learn: past as prologue. PMID- 1592216 TI - Metabolism of 1,2-dibromoethane in the human fetal liver. AB - 1. Toxicity of 1,2-dibromoethane requires bioactivation via glutathione S transferase. Since this enzyme is undetectable in the fetus of several laboratory animal species during early gestation, in vitro studies were carried out with human fetal liver to assess potential fetotoxicity. 2. Glutathione S-transferase occurs abundantly in the human fetal liver cytosol and its titer is equal to or exceeds that found in adult human liver when estimated using 1-chloro-2,4 nitrobenzene as the second substrate. 3. Human fetal liver cytosolic glutathione S-transferase metabolized 1,2-dibromoethane with a high efficiency (mean +/- SD specific activity of 3.10 +/- 0.83 nmol/min/mg protein). This reaction was enzymatic in nature and the rate of conjugation was proportional to the concentration of reduced glutathione, 1,2-dibromoethane and the enzyme present in the reaction medium. 4. A significant bioactivation with a possibility of only limited detoxication via cytochrome P-450-dependent oxidation suggests that human fetus may be at greater risk from 1,2-dibromoethane toxicity than adult. PMID- 1592217 TI - Effects of various cyclooxygenase and lipoxygenase metabolites on guinea-pig cerebral arteries. AB - 1. The effects of some prostanoids, leukotrienes, lipoxins and lipoxin precursors (15-HETE, 15-HPETE) were examined in guinea-pig isolated basilar arteries. 2. The potency order among the prostanoids to elicit contraction was U44069 greater than prostaglandin B2 greater than prostaglandin F2 alpha greater than prostaglandin E2. Leukotriene C4 and D4 were approximately equipotent with prostaglandin B2. 3. Lipoxin A4 and B4 elicited small contractions (4% of the contractile response to 124 mM K+ at 3 x 10(-6) M), which were significantly (P less than 0.02) enhanced by indomethacin. The contractile responses to 15-HETE and 15-HPETE varied considerably (2-102% and 2-56% at 3 x 10(-6) M, respectively) between different vascular segments. 4. Among the leukotrienes, lipoxins and lipoxin precursors, only lipoxin A4 elicited a relaxation, albeit small and transient. 5. In summary, all examined eicosanoids contracted the guinea-pig basilar artery, although the responses to the lipoxins were small but significantly enhanced by cyclooxygenase inhibition. PMID- 1592218 TI - Susceptibility to, tolerance to, and physical dependence on ethanol and barbital in two inbred strains of rats. AB - 1. Ethanol-induced sleep time was significantly longer in F344 than LEW rats. However, there is no difference in barbital-induced sleep time between F344 and LEW. 2. Development of tolerance to ethanol-induced motor impairment was slightly faster in F344 than in LEW rats. While, LEW rats more easily developed tolerance to the impairment by barbital in comparison with F344 rats. 3. F344 and LEW rats were chronically treated with liquid diet containing ethanol or with barbital admixed food. After the termination of ethanol and barbital treatments, various withdrawal signs occurred in F344 rats, including tremor and convulsions, whereas LEW rats showed no convulsions. Withdrawal scores of ethanol and barbital were significantly higher in F344 than in LEW rats. 4. These results suggest that strain differences in physical dependence on ethanol and barbital may be mainly influenced by the susceptibility to ethanol and the development of tolerance to barbital, respectively. PMID- 1592219 TI - Protective effect of a novel vinca alkaloid derivative, vinconate, against alterations in binding sites of second messengers after transient cerebral ischemia in gerbils. AB - 1. We investigated the alterations in binding sites of three major second messengers, phorbol 12,13-dibutyrate, inositol 1,4,5-trisphosphate and forskolin following transient cerebral ischemia in gerbils, and examined the effects of a novel vinca alkaloid derivative, vinconate against the alterations in the binding of the second messengers following ischemia. 2. Transient cerebral ischemia produced by bilateral occlusion of the common carotid arteries was induced for 10 min, and intraperitoneal administration of vinconate (100 mg/kg and 300 mg/kg) was given 10 min before ischemia. 3. Morphological study indicated that transient ischemia can produce severe neuronal damage in striatum, hippocampal CA1 sector and hippocampal CA3 sector. 4. Transient cerebral ischemia caused the postischemic alterations in the binding of three second messengers. 5. The postischemic alterations in the binding of second messengers were ameliorated by pretreatment with vinconate. This effect was especially observed in the striatum which was most vulnerable to ischemia. 6. These findings are discussed in relation to the mechanism of ischemic neuronal damage. PMID- 1592220 TI - Benzpyrene exposure at 15 days of prenatal life reduces the binding capacity of thymic glucocorticoid receptors in adulthood. AB - 1. The offspring of female rats treated with a single dose of benzpyrene on day 15 of gestation showed in adulthood a significant relative decrease in the number of thymic glucocorticoid receptors, without an appreciable decrease in binding affinity. 2. There is experimental evidence that exposure to a hormone analogue in the early stage of organogenesis effects receptor development and the maternal organism fails to confer protection against that untoward influence. PMID- 1592221 TI - Effects of atropine, pirenzepine, imipramine and phenothiazines on the mammalian neuromuscular junction. AB - 1. Trifluoperazine (EC50 = 11.5 nM), chlorpromazine (13.8 microM), imipramine (15 microM), atropine (75.8 microM), and pirenzepine (316.2 microM), all produced neuromuscular facilitation and antagonized the blockade produced by oxotremorine (20 and 30 microM) in the rat isolated diaphragm. 2. These antagonists did not change the responses of curarized diaphragms to direct stimulation, or the twitch tension produced by retrograde injection of acetylcholine. 3. Trifluoperazine (2.5 ng, intra-arterially) reduced the tetanic fade produced by further intra arterial injection of d-tubocurarine (10 micrograms/kg) in the in situ cat tibial muscle. 4. These results indicate that these antagonists may interact with muscarinic autoreceptors to increase acetylcholine output in the neuromuscular junction. PMID- 1592222 TI - Effect of praziquantel and oxamniquine on prostacyclin synthesis by the rat arterial and myometrial tissues. AB - 1. The influence of the two antischistosomal drugs (+/-) praziquantel and (+/-) oxamniquine on PGI2 synthesis by the male rat thoracic aorta and day-20 pregnant rat myometrium in vitro was investigated using a rat platelet antiaggregatory bioassay method. 2. Pretreatment of the tissues with praziquantel (64-512 microM) or oxamniquine (36-288 microM) for 30 min at 37 degrees C significantly inhibited basal PGI2 synthesis in a concentration-dependent manner (P less than 0.005, n = 5-6). 3. Both drugs failed to inhibit PGI2 synthesis in presence of exogenous arachidonic acid (AA) (16.6 microM). 4. Furthermore, they did not antagonize AA (4 nmol kg-1)-induced hypotension in urethane-anaesthetized rats. Thus, the drugs seemed to act via inhibition of phospholipase A2 enzyme (PLA2). 5. The highly lipophilic drugs may interact with membrane phospholipids resulting in prevention of interaction between the substrates and the enzyme's active site. PMID- 1592223 TI - Protective effect of vinconate, a novel vinca alkaloid derivative, on glucose utilization and brain edema in a new rat model of middle cerebral artery occlusion. AB - 1. We investigated the effect of a novel vinca alkaloid derivative, vinconate, against brain damage after focal ischemia induced by a middle cerebral artery (MCA) occlusion in rats. 2. Persistent focal ischemia was induced by 6 hr, and vinconate (50 and 100 mg/kg) was given intraperitoneally twice 10 min and 3 hr after MCA occlusion. 3. Focal ischemia produced the disturbance of glucose metabolism, the increase of water content and the impairment of protein synthesis in the surrounding occluded MCA territory. 4. Vinconate was effective in preventing marked reduction of cerebral glucose utilization in the areas surrounding the occluded MCA territory. 5. Vinconate significantly reduced an increase of water content in the surrounding the occluded MCA territory. 6. Preliminary L-[methyl-14C]methionine autoradiographic study also indicated that vinconate can partly prevent a severe impairment of protein synthesis after focal ischemia. 7. The results indicate that vinconate may ameliorate the disturbance of glucose metabolism, brain edema and the impairment of protein synthesis after persistent focal ischemia, and they also suggest that vinconate has a beneficial effect against brain damage. PMID- 1592224 TI - Comparison of methemoglobin formers in protection against the toxic effects of cyanide. AB - 1. Certain compounds that oxidize hemoglobin to methemoglobin (MHb) also protect against cyanide. 2. Evidence presented here suggests that other mechanisms may be involved. 3. Male Swiss ICR mice were pretreated intraperitoneally (i.p.) with various doses of primaquine phosphate (primaquine), WR6026 (6-methoxy-8-(6 diethylamino-hexylamino) lepidine dihydrochloride), WR238605 (8-[(4-amino-1 methylbutyl) amino]-2,6-dimethoxy-4-methyl-5-(3-trifluoromethylphenoxy) quinoline succinate), p-aminooctoyl-phenone (PAOP), or p-aminopropiophenone (PAPP). 4. The compounds were administered 15 or 60 min before an intramuscular (i.m.) challenge with a 2 x LD50 dose (5.0-5.6 mg/kg) of sodium cyanide (NaCN). 5. Twenty-four hr mortality was assessed and survivors were tested for motor incapacitation. 6. Primaquine, PAPP and PAOP increased survival compared to untreated controls, while the other MHb formers were not effective (P less than 0.05). 7. PAOP is believed to form sufficient MHb only after 3 to 4 hr after administration; however it was found to be effective when administered 15 min before NaCN challenge in this study. 8. This suggests that MHb formation may not be the only factor responsible for PAOP's anti-cyanide efficacy. PMID- 1592225 TI - Capsaicin-like activity of N-ethylmaleimide in rat stomach. AB - 1. N-Ethylmaleimide (NEM) and capsaicin induced a release of calcitonin gene related peptide-like immunoreactivity (CGRP-li) in superfusates from rat gastric corpus. 2. The prior application of capsaicin completely blocked CGRP-li release by NEM while the exposure to NEM reduced the capsaicin-evoked CGRP-li outflow by about 51%. 3. These findings provide evidence that NEM might exert capsaicin-like activity in rat stomach and the release of CGRP-li from capsaicin-sensitive afferent fibres might influence the properties exerted by NEM in this tissue. PMID- 1592226 TI - Effects of exposure of pregnant mice to chlordiazepoxide (CDP) on the development and ultrasound production of their offspring. AB - 1. The effects were studied of injecting pregnant Alderley Park mice with the benzodiazepine agonist chlordiazepoxide (CDP) at doses of 10 and 30 mg/kg during the last 9-10 days of gestation on the early behaviour and development of their offspring. 2. All neonates were fostered to non-treated lactating dams to eliminate maternally-mediated effects. 3. Early development and responses to anxiety-related situations were studied by recording body growth, righting reflex, rooting behaviour, cliff avoidance reflex and ultrasonic "distress" calling. 4. Drug treatment: (a) retarded postnatal body growth; (b) delayed the righting and cliff avoidance reflexes; (c) augmented rooting behaviour and (d) produced an overall increase in ultrasonic calling (but with the higher dose decreasing emission on days 1-2). 5. Exposure to CDP during foetal life retards motor development and physical maturation; produces a sedative/anxiolytic action (especially at high doses) and may modify the sensitivity of GABA-BZP receptor complex to endogenous receptor ligands. PMID- 1592227 TI - A close association between vasoconstrictor-mediated uracil and lactate release by the perfused rat hindlimb. AB - 1. Angiotensin II (5 nM) increased perfusion pressure, O2 uptake and the release of lactate, uracil and uric acid from the perfused rat hindlimb. The release of all three substances was greatest 5 min after commencement of angiotensin II infusion and then decreased over the next 20 min to reach a plateau value that was approx. 2.5-fold basal values. Following removal of angiotensin, pressure, O2 uptake as well as lactate, uracil and uric acid release each returned to pre infusion (basal) values. 2. Cyanide (1 mM) when added during angiotensin II (5 nM) infusion blocked the pressor effect and completely inhibited all O2 uptake. Cyanide (1 mM) also inhibited the angiotensin-induced increase in uric acid, uracil and lactate release, but the effects differed. Whereas uric acid release remained inhibited throughout the cyanide infusion, uracil and lactate release were only temporarily interrupted and a secondary release of both ensued. 3. Nitroprusside (0.5 mM) when added during angiotensin II (5 nM) infusion blocked pressure and O2 uptake. Lactate and uracil release were partly blocked and returned to pre-infusion (basal) values. However uric acid release was totally blocked and no release occurred when nitroprusside was present with angiotensin II. 4. Combined data showed a significant correlation (r = 0.831; P less than 0.001) between effluent lactate and effluent uracil. 5. It is concluded that lactate and uracil release which increase markedly during vasoconstriction of the hindlimb reflect an association between glycolysis and uracil nucleotide turnover within the same tissue, possibly vascular smooth muscle. PMID- 1592228 TI - Adenosine release in morphine-induced hypotension in rats. AB - 1. Following intravenous administration of morphine.HCl a reduction in mean arterial blood pressure (MABP) was produced, quaternary morphine analogue was ineffective. 2. Theophylline and 8-phenyltheophylline administration reduced morphine-induced hypotension. 3. A2 adenosine receptor agonist caused an hypotension while A1 adenosine receptor agonist was ineffective. 4. L-NG-Mono methylarginine administration reduced the hypotensive effect of exogenous A2 agonist while it was ineffective on morphine-induced hypotension. 5. Morphine induced hypotension was increased by pretreatment with dipyridamole, whereas tetrabenazine abolished it. 6. The present study is consistent with previous reports on the central hypotensive action of morphine and propose a role for adenosine release in morphine-induced hypotension. PMID- 1592229 TI - Effects of nicardipine in rats subjected to endotoxic shock. AB - 1. The calcium channel blocker, nicardipine, produced a dose-dependent reduction in the mortality caused by endotoxin in rats. 2. The drug also reduced most of the hematological and gross pathological manifestations of disseminated intravascular coagulation (DIC) caused by endotoxin. 3. The endotoxin-induced monocytopenia but not the granulocytopenia, lymphocytopenia or thrombocytopenia was inhibited by the drug. 4. The results suggest that the protective action of nicardipine is causally related to prevention of the endotoxin-induced DIC and that an effect of the drug on monocytes may be of importance. PMID- 1592230 TI - Comparison of potassium and adenosine cardioplegia with or without verapamil in the isolated guinea pig heart. AB - 1. The cardioprotective effects of adenosine cardioplegia and classical potassium cardioplegia with or without adding verapamil were investigated in isolated guinea pig heart. 2. Four different cardioplegic solutions were used to arrest the hearts which were previously perfused by Krebbs-Henseleit solution. (A) potassium 20 mMol/l. (B) Potassium 20 mMol/l + verapamil 1 micromol/l. (C) Adenosine 10 mMol/l. (D) Adenosine 10 mMol/l + verapamil 1 microgram/l. 3. Both of the adenosine-containing solutions shortened the arrest time and maintained better postischemic recovery according to the potassium cardioplegia. 4. A rapid cardiac arrest was observed when verapamil was added to cardioplegic solutions, on the contrary there was no significant effect on postischemic recovery. PMID- 1592231 TI - Arrhythmogenic potencies of amrinone and milrinone in unanesthetized dogs with myocardial infarct. AB - 1. In dogs with a 2-4 day old myocardial infarct and a predominantly sinus heart rhythm, we examine arrhythmogenic potencies of amrinone (0.5 mg/kg/min, 1 and 3 mg/kg) and milrinone (10 micrograms/kg/min, 75 and 100 micrograms/kg). 2. Amrinone and milrinone significantly reinduced ventricular ectopic beats on day 2 after coronary occlusion. 3. These effects were preceded by a cardioacceleration which intensified as the ventricular arrhythmias developed. 4. Over the following days the arrhythmogenic potencies of these inotropic drugs were modest. 5. Thus, amrinone and milrinone can impair heart rhythm chiefly in a recent myocardial infarct. PMID- 1592232 TI - Salvador Edward Luria (1912-1991). PMID- 1592233 TI - Interspecific comparison of the transformer gene of Drosophila reveals an unusually high degree of evolutionary divergence. AB - The transformer (tra) gene of Drosophila melanogaster occupies an intermediate position in the regulatory pathway controlling all aspects of somatic sexual differentiation. The female-specific expression of this gene's function is regulated by the Sex lethal (Sxl) gene, through a mechanism involving sex specific alternative splicing of tra pre-mRNA. The tra gene encodes a protein that is thought to act in conjunction with the transformer-2 (tra-2) gene product to control the sex-specific processing of doublesex (dsx) pre-mRNA. The bifunctional dsx gene carries out opposite functions in the two sexes, repressing female differentiation in males and repressing male differentiation in females. Here we report the results from an evolutionary approach to investigate tra regulation and function, by isolating the tra-homologous genes from selected Drosophila species, and then using the interspecific DNA sequence comparisons to help identify regions of functional significance. The tra-homologous genes from two Sophophoran subgenus species, Drosophila simulans and Drosophila erecta, and two Drosophila subgenus species, Drosophila hydei and Drosophila virilis, were cloned, sequenced and compared to the D. melanogaster tra gene. This comparison reveals an unusually high degree of evolutionary divergence among the tra coding sequences. These studies also highlight a highly conserved sequence within intron one that probably defines a cis-acting regulator of the sex-specific alternative splicing event. PMID- 1592234 TI - Heritable variation for sex ratio under environmental sex determination in the common snapping turtle (Chelydra serpentina). AB - The magnitude of quantitative genetic variation for primary sex ratio was measured in families extracted from a natural population of the common snapping turtle (Chelydra serpentina), which possesses temperature-dependent sex determination (TSD). Eggs were incubated at three temperatures that produced mixed sex ratios. This experimental design provided estimates of the heritability of sex ratio in multiple environments and a test of the hypothesis that genotype x environment (G x E) interactions may be maintaining genetic variation for sex ratio in this population of C. serpentina. Substantial quantitative genetic variation for primary sex ratio was detected in all experimental treatments. These results in conjunction with the occurrence of TSD in this species provide support for three critical assumptions of Fisher's theory for the microevolution of sex ratio. There were statistically significant effects of family and incubation temperature on sex ratio, but no significant interaction was observed. Estimates of the genetic correlations of sex ratio across environments were highly positive and essentially indistinguishable from + 1. These latter two findings suggest that G x E interaction is not the mechanism maintaining genetic variation for sex ratio in this system. Finally, although substantial heritable variation exists for primary sex ratio of C. serpentina under constant temperatures, estimates of the effective heritability of primary sex ratio in nature are approximately an order of magnitude smaller. Small effective heritability and a long generation time in C. serpentina imply that evolution of sex ratios would be slow even in response to strong selection by, among other potential agents, any rapid and/or substantial shifts in local temperatures, including those produced by changes in the global climate. PMID- 1592235 TI - The proximal end of mouse chromosome 17: new molecular markers identify a deletion associated with quakingviable. AB - Five randomly identified cosmids have been mapped proximal to the Leh66D locus on mouse chromosome 17. Two of these cosmids, Au10 and Au119, map near the neurological mutation quaking. Au119 is deleted in qkviable/qkviable DNA, whereas Au10 is not. Au76 maps to a gene-rich region near the Time locus. The Au76 locus encodes a member of a low copy gene family expressed in embryos, the adult central nervous system and testis. A second member of this family has been mapped to chromosome 15 near c-sis (PDGF-B). At the centromeric end of chromosome 17, Au116 maps near the Tu1 locus, and along with Au217rs identifies a region of unusually high recombinational activity between t-haplotypes and wild-type chromosomes. Au217I and II map to the large inverted repeats found at the proximal end of the wild-type chromosome. In addition, the Au217I and/or II loci encode testis transcripts not expressed from t-haplotypes. PMID- 1592236 TI - Temperature-sensitive cdc7 mutations of Saccharomyces cerevisiae are suppressed by the DBF4 gene, which is required for the G1/S cell cycle transition. AB - When present on a multicopy plasmid, a gene from a Saccharomyces cerevisiae genomic library suppresses the temperature-sensitive cdc7-1 mutation. The gene was identified as DBF4, which was previously isolated by complementation in dbf4 1 mutant cells and is required for the G1----S phase progression of the cell cycle. DBF4 has an open reading frame encoding 695 amino acid residues and the predicted molecular mass of the gene product is 80 kD. The suppression is allele specific because a CDC7 deletion is not suppressed by DBF4. Suppression is mitosis-specific and the sporulation defect of cdc7 mutations is not suppressed by DBF4. Conversely, CDC7 on a multicopy plasmid suppresses the dbf4-1, -2, -3 and -4 mutations but not dbf4-5 and DBF4 deletion mutations. Furthermore, cdc7 mutations are incompatible with the temperature-sensitive dbf4 mutations. These results suggest that the CDC7 and DBF4 polypeptides interact directly or indirectly to permit initiation of yeast chromosome replication. PMID- 1592237 TI - A new property of the maize B chromosome. AB - TB-9Sb is a translocation between the B chromosome and chromosome 9 in maize. Certain deletions of B chromatin from the translocation cause a sharp decrease in B-9 transmission compared to the rate for standard TB-9Sb. The deletions remove components of a B chromosome genetic system that serves to suppress meiotic loss in the female. At least two distinct B-chromosome regions suppress meiotic loss: one on the B-9 and one on 9-B. The system operates by stabilizing univalent B type chromosomes. It allows the univalents to migrate to one pole in meiosis, despite the absence of a pairing partner. The findings reported here are the first evidence for genetic control of meiotic loss by a B chromosome. However, it is proposed that the practice of suppressing meiotic loss is common to the B chromosomes of all species. The need to suppress meiotic loss results from the fact that B chromosomes are frequently unpaired in meiosis and subject to very high frequencies of loss. B chromosomes may utilize one or more of the following methods to suppress meiotic loss: (a) regular migration of univalent B's to one pole in meiosis, (b) enhanced recombination between B chromosomes and (c) mitotic nondisjunction. PMID- 1592239 TI - The effect of constraint on the rate of evolution in neutral models with biased mutation. PMID- 1592238 TI - Associations between nuclear loci and chloroplast DNA genotypes in wild barley. AB - Associations among alleles at nine nuclear loci and three chloroplast DNA (cpDNA) genotypes were assessed in a sample of 247 accessions of the wild barley, Hordeum vulgare ssp. spontaneum. Alleles at two of the nine nuclear loci are marked by length variations in the intergenic spacer region of ribosomal DNA (rDNA), and those of the other seven loci are well characterized allozymes. The three chloroplast DNA (cpDNA) genotypes are marked by restriction fragment length polymorphisms resulting from three polymorphic restriction sites detected by Southern blot hybridization. The analyses were performed by dividing the nine nuclear loci into a series of two-locus subsets and constructing log-linear models to characterize associations between the subsets of two nuclear loci and the cpDNA genotypes. Statistically significant associations were detected between six of the nine nuclear loci and the cpDNA genotypes, either individually as pairwise correlations, or through interaction with another nuclear locus to form three-variate complexes. Although the sample size of the present study was inadequate for statistical evaluation of higher order interactions, the results suggest the existence of interactions in which more than two nuclear loci are involved in associations with cpDNA genotypes. The observed cytonuclear associations appear to result from interplay among a number of evolutionary forces including a mating system of predominant selfing, differentiation among gene pools of local populations, and adaptation of barley genotypes to specific environmental conditions. PMID- 1592240 TI - COTRANS: a program for cotransduction analysis. AB - COTRANS is a program for analyzing cotransduction data. It calculates distances from pairwise cotransduction frequencies, computes crossovers required to obtain each observed recombinant class, and applies rules to draw conclusions about order. The rules are based on the correlation between the frequency of the classes and the number of required crossovers for each possible ordering compatible with the distance calculations. The procedure emulates a geneticist's stepwise analysis of the data by first calculating distances, then looking for obvious three-point ordering conclusions, and finally proceeding to a complete crossover analysis. It reports results from each step of the analysis and an overall conclusion. COTRANS provides significant gains in speed and convenience over hand analysis, particularly for multipoint crosses with several recombinant classes. PMID- 1592242 TI - Looking for the homunculus in Drosophila. PMID- 1592241 TI - Meiosis in Saccharomyces cerevisiae mutants lacking the centromere-binding protein CP1. AB - CP1 (encoded by the CEP1 gene) is a centromere binding protein of Saccharomyces cerevisiae that binds to the conserved DNA element I (CDEI) of yeast centromeres. To investigate the function of CP1 in yeast meiosis, we analyzed the meiotic segregation of CEN plasmids, nonessential chromosome fragments (CFs) and chromosomes in cep1 null mutants. Plasmids and CFs missegregated in 10-20% of meioses with the most frequent type of aberrant event being precocious sister segregation at the first meiotic division; paired and unpaired CFs behaved similarly. An unpaired chromosome I homolog (2N + 1) also missegregated at high frequency in the cep1 mutant (7.6%); however, missegregation of other chromosomes was not detected by tetrad analysis. Spore viability of cep1 tetrads was significantly reduced, and the pattern of spore death was nonrandom. The inviability could not be explained solely by chromosome missegregation and is probably a pleiotropic effect of cep1. Mitotic chromosome loss in cep1 strains was also analyzed. Both simple loss (1:0 segregation) and nondisjunction (2:0 segregation) were increased, but the majority of loss events resulted from nondisjunction. We interpret the results to suggest that CP1 generally promotes chromatid-kinetochore adhesion. PMID- 1592243 TI - A RAD9-dependent checkpoint blocks meiosis of cdc13 yeast cells. AB - Mutations in CDC13 have previously been found to cause cell cycle arrest of Saccharomyces cerevisiae at a stage in G2 immediately preceding the mitotic division. We show here that cdc13 blocks the meiotic pathway at a stage that follows DNA replication, but in this case the spindle has not yet formed nor have the chromosomes undergone synapsis or recombination. This arrest is alleviated by rad9, thus implicating the same checkpoint function that delays mitotic progression when chromosomal lesions are present. An assessment of the spores produced upon alleviation of the meiotic arrest by rad9 reveals that the absence of recombination in strains bearing cdc13 alone is attributable to the RAD9 mediated arrest rather than to other effects of cdc13 lesions. We have tested the possibility that this checkpoint function is important in regulating meiotic progression to permit resolution of recombinational intermediates during ongoing meiosis and have found no evidence that rad9 alters the execution of functions that might depend upon such regulation. We consider the possible role of other checkpoints in yeast meiosis. PMID- 1592244 TI - Selection for early meiotic mutants in yeast. AB - In the yeast Saccharomyces cerevisiae, only a/alpha cells can enter meiosis; a and alpha cells cannot. Because a/alpha cells are typically diploid and a and alpha cells are typically haploid, this cell type restriction ensures that only diploid cells enter meiosis. Entry into meiosis is accompanied by an increase in expression of the IME1 gene; the IME1 product (IME1) then activates IME2 and other meiotic genes. We have found that IME1 expression is toxic to starved haploid cells, presumably because IME1 directs them into meiosis. IME1 toxicity is greater in rad52 mutants, in which meiotic recombination causes lethal damage. Suppressors of IME1 toxicity include recessive mutations in two genes, RIM11 and RIM16 (Regulator of Inducer of Meiosis), that are required for IME1 to activate IME2 expression. RIM11 maps near CIN4 on chromosome XIII. PMID- 1592245 TI - The competitive ability and fitness components of the Methoprene-tolerant (Met) Drosophila mutant resistant to juvenile hormone analog insecticides. AB - The Methoprene-tolerant (Met) mutation of Drosophila melanogaster results in a high (100-fold) level of resistance to the insecticide methoprene, a chemical analog of juvenile hormone. Pest species that are under control with methoprene may therefore have the potential to evolve resistance via a mutation homologous to Met. To evaluate the potential of such mutants to persist in wild populations, we must understand the fitness of flies carrying Met. In the absence of methoprene, Met flies were outcompeted by a wild-type strain both in a multigeneration population cage and in single-generation competition experiments. To determine which fitness component(s) is responsible for the competitive disadvantage, the survival, time of development, and fecundity of flies homozygous for each of five Met alleles were compared with wild type. Small but significant differences were found between the pooled Met alleles and wild type for pupal development time, pupal mortality, and early adult fecundity. These differences result in a large competitive disadvantage. Although Met flies were found to have reduced fitness by these measures, the phenotype is not as severe as might be expected from a knowledge of the disruption of juvenile hormone regulation seen in Met flies. It is concluded that (1) although Met flies have a large advantage under methoprene selection, they will quickly become outcompeted upon relaxation of methoprene usage, (2) even a seemingly severe disruption of juvenile hormone regulation has no drastic effect on the vital functions of the insect and (3) small differences in fitness components can translate into a large competitive disadvantage. PMID- 1592246 TI - A genetic analysis of deltex and its interaction with the Notch locus in Drosophila melanogaster. AB - During Drosophila development networks of genes control the developmental pathways that specify cell fates. The Notch gene is a well characterized member of some cell fate pathways, and several other genes belonging to these same pathways have been identified because they share a neurogenic null phenotype with Notch. However, it is unlikely that the neurogenic genes represent all of the genes in these pathways. The goal of this research was to use a genetic approach to identify and characterize one of the other genes that acts with Notch to specify cell fate. Mutant alleles of genes in the same pathway should have phenotypes similar to Notch alleles and should show phenotypic interactions with Notch alleles. With this approach we identified the deltex gene as a potential cell fate gene. An extensive phenotypic characterization of loss-of-function deltex phenotypes showed abnormalities (such as thick wing veins, double bristles and extra cone cells) that suggest that deltex is involved in cell fate decision processes. Phenotypic interactions between deltex and Notch as seen in double mutants showed that Notch and deltex do not code for duplicate functions and that the two genes function together in many different developing tissues. The results of these investigations lead to the conclusion that the deltex gene functions with the Notch gene in one or more developmental pathways to specify cell fate. PMID- 1592247 TI - A new tool for consultation-liaison funding: modified DRGs to reflect psychiatric comorbidity. AB - Funding for consultation-liaison (C-L) psychiatry remains an overriding obstacle to its implementation and practice. Several methods have been described to access funds for this subspecialty of psychiatry, but none has been enacted as a policy by third party payers to reimburse adequately for the service. In addition, although the consultation portion of the effort can be reimbursed in part in some cases through fee for services, the liaison portion is dependent on the donation of psychiatry time or the largesse of the host department. The efforts at Stanford to capitalize on the findings that psychiatric and medical comorbidity results in prolonged length of hospital stay and increased health resource utilization suggest that specific DRGs would be important patient groups to screen and charge for psychiatric services. Furthermore, DRGs that are accompanied by a high frequency of psychiatric comorbidity are a "target" for an additional funding aliquot to assess and manage the patient's psychiatric status. PMID- 1592248 TI - A profile of the noncompliant patient: a thirty-month review of outpatient psychiatry referrals. AB - Missed appointments to outpatient psychiatry programs have been identified as a major form of noncompliance in the literature. Over a two-and-a-half year period, 874 referrals to the outpatient psychiatry department of a large teaching hospital were examined for significant differences between compliant and noncompliant patients. Noncompliant patients comprised 17.8% of the total number of cases dispositions and were significantly more likely to be single, diagnosed personality disorder or substance abuse, and referred from the Emergency Department than complaint patients. Further analysis of emergency referrals, the single most significant predictor, indicated that patients from this referral source were more likely to be male, unmarried, unemployed or on welfare, and diagnosed personality disorder or substance abuse than referrals from general practice and internal sources. The results are discussed in light of previous research, and recommendations are made for increasing compliance to outpatient appointments. PMID- 1592249 TI - Psychotherapy: past training and current practice. AB - Our 1988 survey of Texas psychiatrists indicates that hospital work is more common, and long-term psychotherapy less common than it had been in the 1982 APA survey. Almost 85% reported long-term psychotherapy experience as residents. Thirty-nine percent reported multiple patients treated for approximately 2 years. Use of audio techniques by resident and teacher in the post-1970-trained group predicted current long-term therapy activity as did an experience of personal therapy and seeing a patient at least twice weekly in training. Concurrent drug use is widely reported for long-term psychotherapy patients and to a lesser degree in psychoanalysis. Our data suggest a shift to increased hospital work and decreased long-term psychotherapy. PMID- 1592250 TI - Decrease of depression during stroke and amputation rehabilitation. AB - Clinical observation had suggested that mild depression occurs after admission for acute medical treatment and then decreases during further hospitalization for rehabilitation treatment. The Geriatric Depression Scale (GDS) was given on admission and discharge to 14 stroke and 17 amputee rehabilitation patients. Each of the two groups showed decreasing GDS scores from beginning to end of the rehabilitation admission. Suggested reasons included: (1) the gradually diminishing effects of stroke and amputation as life crises during the 1-2 month admission, (2) effects of physical improvement on mood and affect, (3) milieu effects of the medical ward, and (4) tendencies for all psychopathology scale scores to decrease on retest. PMID- 1592251 TI - Clock drawing in the screening assessment of cognitive impairment in an ambulatory care setting: a preliminary report. AB - In an exploratory study to assess the utility of clock drawing as a screening test for cognitive impairment in medical/surgical outpatients, clock drawing and the 6-item Orientation-Memory-Concentration Test (OMCT) were administered to over 400 randomly selected ambulatory patients over the age of 55 in a busy inner-city hospital. The clock drawing test was completed by 431 patients, and 471 completed the OMCT. Clock drawing errors suggestive of moderate-to-severe cognitive impairment were found in 42.7% of patients; OMCT errors suggestive of moderate-to severe cognitive impairment were found in 35.4% of the population tested. The clock drawing test might represent a quick-screen for cognitive impairment in an older general medical/surgical outpatient population, and might help identify patients not otherwise recognized as potentially unable to fully understand treatment recommendations. PMID- 1592252 TI - The misdiagnosis of conversion disorder in a psychiatric emergency service. PMID- 1592253 TI - The treatment of mental disorders in general medicine settings. PMID- 1592255 TI - Imaging of brain electrophysiologic activity: applications in psychiatry. AB - Recent advances in computer technology make it relatively easy to generate color images representing the electrophysiologic activity of the brain. Because of the visual appeal of the images, and their similarity to computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) scans, there has been wide interest in these methods. Thorough understanding of these techniques is necessary to appreciate their strengths and limitations, and their proper application. This article explains the types of studies that are usually done, compares these methods with other imaging techniques, outlines their limitations, summarizes the literature on their use in psychiatry, and describes clinical situations in which these tests may be useful. This information will help the reader interpret clinical reports and research studies that employ these methods, evaluate representations made by commercial vendors of imaging systems, and understand the role these tests can play in his or her daily clinical practice. PMID- 1592254 TI - A randomized trial of psychiatric consultation with distressed high utilizers. AB - This study reports the results of a randomized trial of a psychiatric consultation intervention with distressed, high utilizing patients of 18 physicians in two primary care clinics. Psychiatric consultation was associated with a significant increase in the use of antidepressants in intervention patients compared with controls in the first 6 months after intervention. Intervention patients were also significantly more likely to continue antidepressant treatment than control patients. The primary care physicians receiving psychiatric consultations increased the rate of prescribing antidepressant medications in their practice from 32 prescriptions filled per 1,000 visits before their participation in four consultations to 44 new prescriptions per 1,000 visits in the 12-month period after. There were no significant differences between intervention patients and controls at 6 and 12 months after randomization in psychiatric distress, functional disability, or utilization of health care (ambulatory visits, radiographic and laboratory testing services, admissions to inpatient medical care). PMID- 1592256 TI - The Drosophila pourquoi-pas?/wings-down zinc finger protein: oocyte nucleus localization and embryonic requirement. AB - The pourquoi-pas? (pqp) gene of Drosophila melanogaster encodes a Cys2/His2 zinc finger protein and is abundantly transcribed in adult ovaries. During oogenesis, we immunodetected the pqp protein in the nucleus of nurse cells at stages 1-6, in a spherical structure within the oocyte nucleus at stages 7-9, and uniformly distributed in the oocyte nucleus and in nurse cell nuclei at later stages. The pqp protein is also present at a lower level in the nuclei of follicle cells, embryos, and larvae. By means of a polymerase chain reaction (PCR) screen, we recovered three independent and phenotypeless P-element insertions at the pqp locus. In a second step, two excision-induced deletions of the pqp gene were isolated after mobilization of one of these P elements. The pqp mutants display zygotic (spread and drooping wings, cross-vein defects, extra bristles) and maternal (embryonic lethality) recessive phenotypes. The chromosomal position (98EF) of the pqp gene and the drooping wing phenotype of the pqp mutants agree with the hypothesis that the pqp gene is the wings down (wdn) gene for which T.H. Morgan isolated (and lost) mutants in the 1920s. This is the first reported occurrence of a zinc finger protein in the nucleus of the Drosophila oocyte. PMID- 1592257 TI - Disruption of the sporulation-specific gene spiA in Dictyostelium discoideum leads to spore instability. AB - The spiA gene of Dictyostelium is expressed specifically in prespore cells and spores during culmination, the final stage of development during which prespore and prestalk cells undergo terminal differentiation to form spores and stalk. We have used homologous recombination to delete this gene and have characterized the resulting phenotype. The spiA- strains develop normally and produce spores that are indistinguishable from those of wild-type strains by transmission and scanning electron microscopy. Mutant spores have normal viability when assayed soon after the completion of development, but, as the spiA- spores age, they lose viability more rapidly than those of the spiA+ parent. The drop in viability is more pronounced when spores are submerged in dilute buffer at a concentration that does not allow germination; after 11 days submerged, the viability of spiA- spores is 10(5)-fold reduced, whereas that of the parent is decreased only 10 fold. Reinserting an intact copy of the spiA gene into a spiA- strain restores the stability of its spores. The product of the spiA gene, Dd31, was identified on Western blots as a 30-kD protein using an antibody raised against a fusion protein containing a portion of the coding sequence. Dd31 is associated with the inner face of spore coat fragments in a detergent-resistant manner. This location is consistent with its observed role in maintaining stability of the spores. PMID- 1592258 TI - Control of 4-8S RNA transcription at the midblastula transition in Xenopus laevis embryos. AB - Transcription of Xenopus laevis U1 snRNA genes is subject to a precise program with respect both to the timing of activation at the midblastula transition (MBT) and to the relative levels of the two embryonic U1 RNAs (xU1b1 and b2) that are made. Here, we demonstrate that exogenous xU1b genes injected into developing X. laevis embryos come under the same controls as the endogenous genes. Injected U1 genes, unlike exogenous RNA polymerase III genes, remain quiescent until MBT and their activation at MBT requires protein synthesis during the early cleavage stages. Significantly, the onset of 4-8S RNA transcription occurs at the normal time, even when the DNA content of the embryo has been increased by injection of exogenous DNA or reduced through cleavage arrest, indicating that transcriptional activation at MBT is independent of the ratio of DNA (nucleus) to cytoplasm. In cleavage-arrested (coenocytic) embryos, the reduced level of DNA at MBT results both in a decrease in snRNA and tRNA synthesis (reflecting the lower gene dosage) and in a prolonged synthesis of large amounts of unusual RNA polymerase III transcripts, OAX RNAs. In normally cleaving embryos, small amounts of these unstable OAX RNAs (encoded by satellite I DNA) are synthesized only briefly at MBT. Our demonstration that RNA and DNA metabolism is aberrant in cleavage arrested embryos requires reevaluation of previous experiments on transcriptional activation that utilized such coenocytic embryos. PMID- 1592259 TI - Nonsense mutations inhibit splicing of MVM RNA in cis when they interrupt the reading frame of either exon of the final spliced product. AB - mRNAs R1 and R2 of the autonomous parvovirus minute virus of mice (MVM), which encode the viral nonstructural proteins NS1 and NS2, respectively, are processed in an ordered splicing pathway in which R2 is generated from mature spliced R1. Introduction of translation termination signals into these genes alters the processing of these RNAs; there is a significant (up to fourfold) increase in the accumulated steady-state levels of R1 relative to R2, when compared with wild type levels, although the total accumulated levels of R1 plus R2 remain the same. The increase in accumulated R1 relative to R2 in mutant infected or transfected murine cells is independent of RNA stability and transport and decreases, in a polar manner, with the distance of the inserted termination signal from the shared initiation codon for NS1 and NS2 at nucleotide 260. The increased ratio of R1 to R2 is a consequence of the artificially introduced translation termination signals acting in cis rather than in the absence of a functional viral gene product. These mutations have an effect when they interrupt previously open reading frames in either exon of the spliced product R2. Nonsense mutations that are located in the second exon of R2 inhibit splicing of R1 to R2 only when they interrupt an open reading frame (ORF) that has the potential, after normal splicing, to be joined in-frame with the initiating AUG. These results suggest that nonsense mutations inhibit splicing of R1 to R2 by influencing the mechanism by which exons are defined in murine cells. PMID- 1592260 TI - Distinct molecular signals for nuclear import of the nucleolar snRNA, U3. AB - Export to the cytoplasm of U3 RNA transcribed from a rat U3 gene injected into the nucleus of Xenopus oocytes indicates that the biogenesis of U3 RNA, like that of the previously studied Sm-precipitable nucleoplasmic snRNAs (U1, U2, U4, and U5), includes a cytoplasmic phase. The regulation of import of the U3 snRNA into the nucleus has been analyzed by injection of synthetic human U3 transcripts into the cytoplasm of Xenopus oocytes. Binding of the major autoantigenic protein of the U3 snRNP, fibrillarin, and cap trimethylation can occur in the cytoplasm, but neither are required for import. The 3'-terminal 13 nucleotides are required for optimal import and cap trimethylation and participate in a phylogenetically conserved U3 structural element, a short 3'-terminal stem. An artificial construct containing the 3'-terminal 13 nucleotides, including the 3'-terminal stem, but only 56 nucleotides of the 217 nucleotides in U3, appears to be sufficient for import. The presence of the 3'-terminal stem in all snRNAs known to be imported suggests that it might be a universal element required for nuclear import. PMID- 1592261 TI - A gene trap approach in mouse embryonic stem cells: the lacZ reported is activated by splicing, reflects endogenous gene expression, and is mutagenic in mice. AB - We have confirmed that the gene trap vector pGT4.5 creates spliced fusion transcripts with endogenous genes and prevents the synthesis of normal transcripts at the site of integration. cDNA was prepared to the lacZ fusion transcript in three ES cell lines to recover endogenous exon sequences upstream of lacZ. Each of the clones detected a unique-sized endogenous transcript, as well as the fusion transcript in the ES cell line from which the clone was derived. Sequence analysis of these clones and larger clones isolated from a random-primed cDNA library showed that the splice acceptor was used properly. For two insertions, the expression patterns of the lacZ reporter and the associated endogenous gene were compared in situ at three embryonic stages and were found to be similar. Three gene trap insertions were transmitted into the germ line, and abnormalities were observed with two of the three insertions in the homozygous state. RNA obtained from mice homozygous for the two mutant gene trap insertions was analyzed for normal endogenous transcripts and negligible amounts were detected, indicating that little splicing around the gene trap insertion occurred. This work demonstrates the capacity of the gene trap vector to generate lacZ fusion transcripts, to accurately report endogenous gene expression, and to mutate the endogenous gene at the site of integration. PMID- 1592262 TI - Inactivation of the human beta-globin gene by targeted insertion into the beta globin locus control region. AB - The human beta-globin locus control region (LCR) is a complex regulatory element that controls the erythroid-specific expression of all cis-linked globin genes. The LCR is composed of five DNase I hypersensitive sites (HS) spanning 16 kb and located greater than 50 kb upstream of the beta-globin gene on chromosome 11. Constructs containing all or some of these HS have been shown to produce high level erythroid-specific expression of linked genes in transgenic mice and transfected cells. In all transgenic and transfection experiments reported to date, however, the spatial relationships between the LCR and globin genes have been disrupted. We have used homologous recombination (HR) as an approach to gain insights into the potential interactions between the LCR and globin genes in their native locations. A hygromycin B resistance (hygro(R)) gene was inserted into the human beta-globin LCR on chromosome 11 in a mouse/human hybrid erythroid cell line that expresses the human beta-globin gene after the induction of differentiation. As a consequence of this targeted insertion, the beta-globin gene is transcriptionally inactive and not inducible. In contrast, the hygro(R) gene within the LCR is inducible, whereas randomly integrated hygro(R) genes are not inducible in these cells. The chromatin structure of the targeted locus is also altered. A new DNase I HS is present in the enhancer/promoter of the hygro(R) gene inserted into the LCR, whereas a HS normally present in the LCR 3' to the insertion is lost and the beta-globin gene promoter HS is not detectable. These results are consistent with the promoter/enhancer competition model for LCR function and globin gene switching. PMID- 1592263 TI - A novel modulator domain of Ets transcription factors. AB - The ets gene family is composed of several oncogenes and codes for transcription factors. The Ets proteins have a similar sequence called the ets domain and bind to the core motif A/CGGAA. We show here that several members of the ets family have different trans-activating properties. The ets domain of Ets-1 is required for DNA binding. Adjacent to this domain there is a novel element that inhibits DNA binding. It appears to alter the structure of the DNA-binding domain before it interacts with DNA. There is a similar sequence in Ets-2 that also inhibits DNA binding. This sequence is absent in alternative splice products of h-Ets-1. PU1, the most distantly related member of the ets gene family, lacks this novel element. It has a distinct DNA-binding specificity that is determined by DNA sequences outside the core motif. These results have important implications for both the oncogenic and normal functions of ets family members. PMID- 1592264 TI - Interaction of murine ets-1 with GGA-binding sites establishes the ETS domain as a new DNA-binding motif. AB - The proto-oncogene ets-1 is the founding member of a new family of eukaryotic transcriptional regulators. Using deletion mutants of murine ets-1 cDNA expressed in Escherichia coli, we show that the DNA-binding domain corresponds closely to the ETS domain, an 85-amino-acid region that is conserved among ets family members. To investigate the specificity of DNA binding of the ETS domain, we mapped the DNA contacts of a monomeric Ets-1 fragment by chemical protection and interference assays. DNA backbone interactions span a 20-nucleotide region and are localized on one face of the helix. Close phosphate and base contacts are restricted to 10 central nucleotides. Contacts map to the major groove in the center of the site. Flanking minor groove interactions also are predicted. To determine the sequence preference in the close contact zone, we selected a pool of high-affinity binding sites using a purified Ets-1 carboxy-terminal fragment. Our Ets-1-selected consensus, 5'-A/GCCGGAA/TGT/C-3', differs from the binding consensus for the Drosophila ETS domain protein E74A, suggesting that specificity of action of ets family members is mediated by the ETS domain. Compared to other well-characterized classes of DNA-binding proteins, Ets-1 produces a unique pattern of DNA contacts. These studies demonstrate that the ETS domain proteins bind DNA in a novel manner. PMID- 1592265 TI - A ubiquitous factor is required for C/EBP-related proteins to form stable transcription complexes on an albumin promoter segment in vitro. AB - The liver-enriched transcription factor CCAAT/enhancer binding protein (C/EBP) binds to numerous liver-specific promoters, yet the mechanism by which the protein stimulates transcription has not been described. The serum albumin promoter, which is liver specific, contains a strong C/EBP-binding site tightly juxtaposed to a binding site for the ubiquitous factor nuclear factor-Y (NF-Y). The binding of C/EBP impairs the binding of NF-Y; yet surprisingly, this arrangement leads to strong synergistic activation of a minimal promoter in liver nuclear extracts. Transcriptional synergism is manifested by NF-Y facilitating the ability of C/EBP to form preinitiation complexes that are stable through multiple rounds of transcription. Binding by itself, C/EBP stimulates transcription weakly without forming stable complexes, and moving the NF-Y binding site 10 bp away from the C/EBP site increases NF-Y binding in the presence of C/EBP but reduces the efficiency of stable complex formation and transcriptional synergism. These findings show that C/EBP requires precise positioning next to a ubiquitous factor for optimal formation of stable complexes and provides a model to understand the dramatic activation of the albumin gene in hepatic development. PMID- 1592266 TI - Urinary incontinence in the aged, Part 1: Patient evaluation. AB - Urinary incontinence affects a large percentage of persons over age 65 and predisposes them to social isolation, depression, and premature nursing home placement. Transient incontinence may be precipitated by such factors as delirium, infection, atrophic vaginitis/urethritis, medication use, and restricted mobility. Persistent incontinence may be of the urge, stress, overflow, or functional type. The patient history and simple tests such as bedside urodynamics generally isolate the cause. In this first part of a two-part article, we discuss the primary care evaluation of the older patient with urinary incontinence. In part 2 (page 37), we discuss a primary care management strategy. PMID- 1592267 TI - Urinary incontinence in the aged, Part 2: Management strategies. AB - Treatments for urge incontinence associated with uninhibited bladder contractions include medications with anticholinergic and smooth muscle relaxant properties as well as habit training, bladder retraining, contingency therapy, and biofeedback. Pelvic floor (Kegel) exercises improve stress incontinence in 60 to 90% of female patients. For patients who fail to improve with pelvic floor exercises, a combination of an alpha-adrenergic agent and conjugated estrogen is recommended. Surgery is particularly effective in elderly women with significant pelvic prolapse. Management of overflow incontinence requires surgery or intermittent/chronic catheterization. Functional incontinence may be improved with correction of the underlying disorder and availability of a motivated caregiver. PMID- 1592268 TI - Aging and mental health: diagnosis of dementia and depression. AB - In this second segment of a panel discussion on aging and mental health, panelists focus on the primary care evaluation and management of the patient with dementia, including differential diagnosis of depression. Other topics of discussion include the roles of psychiatric referral and psychotherapy in patient management, suicide prevention, and alcoholism in elderly patients. PMID- 1592269 TI - Musculoskeletal disorders: improving diagnostic accuracy with MRI. AB - Magnetic resonance imaging (MRI) is gaining wider acceptance for the diagnosis of musculoskeletal disorders in the elderly, including internal joint derangements, neoplasms, and osteonecrosis. For internal derangement of large joints such as the knee, MRI is a noninvasive alternative to arthrography and offers excellent visualization. It plays an important role in the diagnosis and staging of primary and secondary neoplasms, including both osseous and soft tissue sarcomas. MRI is also indicated for diagnosing osteonecrosis that cannot be detected using other imaging modalities. PMID- 1592270 TI - Risk factors for MI--and lawsuits. PMID- 1592271 TI - Hypospadias repair in elderly patients. AB - Although surgical repair of hypospadias has been performed for decades, some older men with this anomaly have never been treated or even referred. Age alone should not be a contraindication for surgery. Rather, the physician needs to consider the degree of urethral stricture and voiding impairment caused by the disorder and the extent those factors affect the patient's quality of life. PMID- 1592272 TI - Medicare squeezes urban MDs. PMID- 1592273 TI - Reactions of glutathione and glutathione radicals with benzoquinones. AB - The reactions of glutathione (GSH) and glutathione radicals with a series of methyl-substituted 1,4-benzoquinones and 1,4-benzoquinone have been studied. It was found that by mixing excess benzoquinone with glutathione at pH above 6.5, the products formed were complex and unstable. All of the other experiments were carried out at pH 6.0, where the main product was stable for several hours. Stopped-flow analysis allowed the measurement of the rates of the rapid reactions between GSH and the quinones, and the products were monitored by High Performance Liquid Chromatography (HPLC). The rates of the reactions vary by five orders of magnitude and must be influenced by steric factors as well as changes in the redox states. It was observed that simple hydroquinones were not formed when the different benzoquinones were mixed with excess GSH and suggests that the initial reaction is addition/reduction rather than electron transfer. In the presence of excess quinone, the hydroquinone of the glutathione conjugate is oxidized back to its quinone. The rates of the reaction were measured. By using the technique of pulse radiolysis, it was possible to measure the reduction of the quinones by GSSG.- and the oxidation of hydroquinones by GS(.). It is proposed that the appearance of GSSG in reactions of quinones with glutathione could be due to oxidation of the hydroquinone by oxygen and the subsequent superoxide or H2O2 promoting the oxidation of GSH to GSSG. PMID- 1592274 TI - Role of physiological antioxidants in chromium(VI)-induced cellular injury. AB - Chromium(VI) compounds are well known to be potent toxic and carcinogenic agents. Because chromium(VI) is easily taken up by cells and is subsequently reduced to the trivalent form, the formation of chromium(III) or other intermediate oxidation states such as chromium(V) and (IV) is believed to play a role in the adverse biological effects of chromium(VI) compounds. Recent in vitro studies have shown that this reduction process generates free radical species such as active oxygen radicals. Furthermore, physiological antioxidants are reported to modify the genotoxic and toxic effects of chromate. This article reviewed the recent in vitro and in vivo studies of the effects of antioxidants including active oxygen scavengers; glutathione; vitamins B2, E, and C, on chromate-induced injury such as DNA lesions; lipid peroxidation; enzyme inhibition; cytotoxicity; mutation; and so on. In addition, the mechanism of action of these antioxidants was discussed with respect to the formation of active oxygen radicals and paramagnetic chromium such as chromium(V) and (III). Such studies may help elucidate the mechanism of chromium(VI) toxicity as well as the mechanism of protection. PMID- 1592275 TI - Oxidants and the pathophysiology of burn and smoke inhalation injury. AB - A skin burn is a common traumatic injury that results in both local tissue damage and a systemic mediator-induced response. There is evidence of both local and systemic oxidant changes manifested by lipid peroxidation in animal burn models and also in burned man. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources. Animal studies have also demonstrated decreased burn edema, and also decreased distant organ dysfunction with the use of antioxidants, suggesting a cause-and-effect relationship, which needs to be tested in man. Smoke inhalation injury, a chemical injury to the airways caused by incomplete products of combustion, is frequently seen in conjunction with a body burn. Lipid peroxidation, both in lung and in distant organs, is also seen with this injury. The combined body burn and smoke inhalation injury lead to a marked increase in mortality rate and also an increase in the degree of generalized oxidant release and lipid peroxidation. Although data in man are limited, the available information, along with that from animal research on burns and smoke inhalation, indicates oxidants may well play a key role, and antioxidants may be of clinical therapeutic use. PMID- 1592276 TI - Chemotherapy for ovarian cancer: is there a best buy? PMID- 1592278 TI - Gynecologic complications associated with long-term adjuvant tamoxifen therapy for breast cancer. AB - The antiestrogen tamoxifen was originally introduced as a therapy for advanced breast cancer. Today, tamoxifen is used to treat selected patients with all stages of breast cancer, and trials are underway to evaluate its effectiveness as a potential breast cancer preventive. When tamoxifen is used as an adjuvant or preventive, extended patient survival times can be expected, and concerns about iatrogenic complications arising from long-term treatment become important. This review discusses currently available laboratory and clinical data regarding the toxicology of tamoxifen and focuses in particular on the gynecologic complications potentially associated with long-term tamoxifen administration. PMID- 1592277 TI - Long-term results of a randomized trial comparing cisplatin with cisplatin and cyclophosphamide with cisplatin, cyclophosphamide, and adriamycin in advanced ovarian cancer. GICOG (Gruppo Interregionale Cooperativo Oncologico Ginecologia), Italy. AB - We report the long-term results of a randomized trial comparing cisplatin (P) with cisplatin and cyclophosphamide (CP) with cisplatin, cyclophosphamide, and adriamycin (CAP) in advanced ovarian cancer. Overall, this update confirms previously published data on 529 cases. Median survival times for the three treatments--CAP, CP, and P--are, respectively, 23, 20, and 19 months. The differences among the three arms are still nonsignificant and the estimated percentage survival at 7 years and confidence limits are, respectively, 21.7 (14.9-28.4), 17.0 (11.0-22.9), and 12.2 (6.9-17.4). According to the results of the Cox regression model on prognostic factors, higher grading, a larger residual tumor size, and performance status less than 80 (Karnovsky) all were independently associated with a poorer outcome, while a serous histotype was related to a better prognosis. The other variables (age, stage, center, type of surgery) initially included in the model did not appear to be significantly related to prognosis. The implications of these long-terms results relative to the application of combination chemotherapy with CAP or CP are discussed. PMID- 1592279 TI - Immunotherapy of ovarian cancer. II. In vitro generation and characterization of lymphokine-activated killer T cells from the peripheral blood of recurrent ovarian cancer patients. AB - We examined the in vitro sensitivity of continuous ovarian cancer cells to lymphokine-activated killer T cells (T-LAK) alone or in combination with cytokines. Lymphocyte viability in T-LAK cultures generated from normal donors and ovarian cancer patients declined in the first 2 to 4 days; however, the remaining cells in these cultures maintained a constant rate of proliferation for long periods in vitro. These cells became 90-95% CD3+ TCR+ -alpha/beta T-cells after 7-10 days in culture. The T-LAK cells from normal donors and cancer patients expressed an equal ability to induce lysis of a panel of human target cells (NK-sensitive K562, NK-insensitive RAJI, and two human ovarian tumor lines, SKOV-3 and OVCAR-3), demonstrating that they are nongenetically restricted killers. Preincubation of either the effector or target cells with tumor necrosis factor or interferon-gamma or addition of these cytokines directly to cytolytic assays did not alter the degree of cell lysis in vitro. This is a method for generating large numbers of autologous, cytolytically active T-LAK cells from the blood of ovarian cancer patients that could be employed in adoptive intraperitoneal immunotherapy. PMID- 1592280 TI - The prognostic significance of surgical staging for carcinoma of the endometrium. AB - This study is based on a retrospective review of 156 patients with endometrial carcinoma from 1978 through 1984 who underwent primary surgical evaluation. All cases were retrospectively restaged using the newly adopted FIGO surgical staging. The preoperative FIGO clinical stage distribution for this study was as follows: 121 (77.6%) Stage I, 22 (14.1%) Stage II, 5 (3.2%) Stage III, 2 (1.3%) Stage IV, and 6 (3.8%) unstaged patients. Most patients had TAH-BSO with a collection of peritoneal washings and retroperitoneal lymph node sampling. Surgical staging revealed 122 (78.2%) Stage I, 9 (5.8%) Stage II, 12 (7.7%) Stage III, and 13 (8.3%) Stage IV patients. Surgery upstaged 12.4% of clinical Stage I. In clinical stage II, 59.0% were downstaged while 27.3% were upstaged. For clinical Stage III, 60.6% were upstaged, but no downstaging occurred. No change in stage occurred for clinical Stage IV patients. Ninety-seven surgically staged patients received no adjuvant therapy. The remaining 59 patients had adjunctive treatment which consisted of radiotherapy (59.3%), hormonal therapy (25.4%), chemotherapy (5.1%), or combined modality treatment (10.2%). All patients were followed until death or a minimum of 5 years (60-139 months; median, 82 months) with the exception of 13 patients who were lost to follow-up (2-58 months; median, 34 months). Five-year survival by clinical staging was as follows: 86.2% for Stage I, 85.9% for Stage II, and 0% for Stage III and IV. Five-year survival by surgical staging was 90.6% for Stage I, 85.7% for Stage II, 58.3% for Stage III, and 0% for Stage IV. The 13 patients who were lost to follow-up were censored in all survival analyses at the time of last contact. Stepwise regression analysis using a parametric proportional hazards model identified surgical stage as the most significant prognostic factor (P = 0.02). Univariate analysis showed that patients with surgical Stage IC had significantly worse prognosis (75.0%, 5 years) than those in surgical Stage IA (93.8% 5 YS) or IB (95.4% 5 years). In summary, this study demonstrates that surgical staging as recommended by FIGO is indicated to accurately determine the initial extent of disease in endometrial carcinoma. In addition, surgical staging is the strongest predictor of survival. Deep myometrial invasion appears to be a significant independent prognostic factor within surgical Stage I. The role of adjunctive radiotherapy in Stage I disease awaits the results from an ongoing multi institutional, prospectively randomized trial. PMID- 1592281 TI - Formation of a vagina at the time of exenteration. AB - The formation of an artificial vagina at the time of exenteration has been described. Femoral gluteal flaps forming a tube suspended to the iliopectineal ligament appeared to give the most satisfactory results. PMID- 1592282 TI - Results of treatment in stage IIB squamous cell carcinoma of the uterine cervix: comparison between two and one intracavitary insertion. AB - To compare the results of treatment in stage IIB squamous cell carcinoma of the uterine cervix of two treatment regimens, two radium insertions vs one insertion, a prospective randomized study was carried out at Ramathibodi Hospital from 1 January 1983 to 31 December 1986, and the results were evaluated at the end of March 1991. The patients in treatment I (90 cases) received 40-41.4 Gy whole pelvic external irradiation and two intracavitary radium insertions, while patients in treatment II (53 cases) received 50.0-50.4 Gy and one intracavitary insertion. Both groups received the same total dose at point A, about 85-90 Gy. At 4 and 5 years, by the Kaplan-Meier survival curve, the disease-free survivals were 76 and 76% vs 79 and 79%, respectively, in treatment I and treatment II, which showed no significant difference by the log-rank test. Both groups had comparable serious complication rates, 0% vs 1.9%, respectively. However, grade I complications in treatment II, 35.8%, were higher than those in treatment I, 17.8% (P less than 0.01). Therefore, we concluded that treatment II provided the same disease-free survival and a very low rate of serious complications. To replace treatment I, the dose at the rectum and urinary bladder should be maintained with caution. PMID- 1592283 TI - Comparative evaluation of pirarubicin and adriamycin in gynecologic cancer cell lines. AB - Pirarubicin (PIRA) has been shown to have improved potency with less cardiac toxicity in several phase I and II clinical trials in Japan and Europe. Since Adriamycin (DXR) remains one of the most potent drugs in treatment of gynecologic cancers, this derivative has the potential to become an important chemotherapeutic agent. In this study, we compared the performance of these two drugs against a panel of 10 gynecologic cancer cell lines. The ATP chemosensitivity assays were used to determine dose-response curves. Flow cytometry was used to study cell kinetic response to both drugs. Using an IC50 value of 0.2 micrograms/ml as a cutoff for drug sensitivity, 4 cell lines, ECC1, HEC1B, BG1, and SKOV3, were considered resistant to DXR. By comparing IC50s, PIRA was 3.4 +/- 0.4 times more potent than DXR (P = 0.05). The other 6 cell lines, AN3, AE7, HEC1A, CAOV3, SKUT1B, and ME180, were considered sensitive to DXR. In this group of cell lines, PIRA was 1.6 +/- 0.3 times more potent than DXR (P = 0.5). Both PIRA and DXR elicited a spectrum of cell kinetics. By comparing the magnitude of G2 blocks at 0.1 micrograms/ml, PIRA was approximately 2-5 times more potent than DXR in SKUT1B, HEC1A, and BG1 cell lines. PIRA also displayed a reverse dose-response pattern of G2 block so that at high dose, cell cycle kinetics would mirror those of untreated controls. This observation supports the presence of a resistant tumor subpopulation and the concept of tumor heterogeneity. PMID- 1592284 TI - New pelvic sonoangiography for detection of endometrial carcinoma: a preliminary report. AB - Pelvic sonoangiography (PSAG) using transvaginal color Doppler was done on 16 postmenopausal patients with abnormal uterine bleeding. Seven women had no endometrial carcinoma and nine had carcinoma. No flow was detected around and within the endometrium in noncancer patients. PSAG showed a feeder artery (blood flow with pulsation that runs into and clings to the tumor) in all patients with endometrial carcinoma, and intratumor blood flow (a mixture of pulsating and constant flow within the tumor) was evident in 7 of 9 patients with endometrial carcinoma. These findings were confirmed by conventional pelvic angiography. In the diagnostic evaluation of PSAG for endometrial carcinoma, both sensitivity and specificity were 100%. We conclude that PSAG with transvaginal color Doppler can be used to detect endometrial carcinoma in postmenopausal women with abnormal uterine bleeding and that this method might be applicable to selecting patients who really require diagnostic surgery for endometrial cancer. PMID- 1592285 TI - The use of ATP bioluminescence assays in selecting a drug screen panel for chemosensitivity testing of uterine cancer cell lines. AB - The ATP bioluminescence assay has demonstrated a strong potential to become a clinical assay for chemosensitivity testing. Currently, chemotherapy of gynecologic cancers remains controversial and empirical. To optimize the patient's chance of survival and to justify related toxicities, the chemoregimen should be individualized and based on the patient's chemosensitivity profiles. This study was performed to identify a panel of active drugs against uterine cancer cell lines for possible use in future chemosensitivity testing. We used the ATP chemosensitivity assays to screen 12 common cytotoxic agents against six uterine cancer cell lines. Drug concentrations required for a 50% surviving fraction were defined as IC50s. When using an IC50 of 0.21 PPC (peak plasma concentration) as a cutoff value for sensitivity, the following 8 drugs were considered effective for uterine cancer cell lines: actinomycin D, Adriamycin, vinblastine, etoposide, 5-fluorouracil, methotrexate, cytosine arabinoside, and mitomycin-C. Meanwhile, 4 drugs, cisplatin, 4OH-Cytoxan, bleomycin, and Alkeran with mean IC50s of 2.1 +/- 0.7, 0.8 +/- 0.1, greater than 5.0, and 0.75 +/- 0.36 PPC, respectively, were considered inactive or partially active with higher IC50s than peak plasma concentrations. In conclusion, the above panel of promising drugs can be further tested in animal models or human cancer specimens for possible use in chemosensitivity testing of uterine cancer patients. PMID- 1592286 TI - A comparative study of radical vulvectomy and modified radical vulvectomy for the treatment of invasive squamous cell carcinoma of the vulva. AB - Forty-five patients who underwent a modified radical vulvectomy for invasive squamous cell carcinoma of the vulva were compared with forty-five patients who underwent radical vulvectomy for similar lesions. Vulvar wound infection and breakdown were infrequent in both groups. Anal incontinence developed postoperatively in five of the modified radical vulvectomy patients and in none of the radical vulvectomy patients. Urinary incontinence developed postoperatively in two of the modified radical vulvectomy patients and in seven of the radical vulvectomy patients. Possible reasons for these differences are discussed. One invasive local recurrence (2.2%) developed in the modified radical vulvectomy group and two (4.4%) local recurrences developed in the radical vulvectomy group. A modified radical vulvectomy appears to be efficacious for the vulvar phase of treatment of localized invasive squamous cell carcinoma of the vulva. PMID- 1592287 TI - Supravaginal uterine amputation in Denmark 1978-1988 and risk of cancer. AB - In Denmark, total rather than subtotal hysterectomy has been recommended as treatment for benign conditions of the uterine corpus, primarily due to the risk of cervical cancer in the residual stump. Due to possible benefits during and after surgery, it has recently been argued that total hysterectomy for benign conditions could be substituted by subtotal hysterectomy, particularly since cancers of the cervix are declining as a consequence of screening. Cancer risk following supravaginal uterine amputation among 1104 Danish women undergoing operations during 1978-1988 was studied using record linkage techniques with the Danish Cancer Registry. No overall cancer risk, nor an overall increased risk of cancers coded as cervical, was observed. However, a 3.3 to 5.0-fold increased risk for cervical cancer was observed among women whose operations occurred at 50 years of age or older, possibly reflecting an increased risk of cancer in the endocervical area or in remaining uterine tissue. This observation, together with the difficulties in treating a cervical cancer of the stump when it does occur, should be taken into account before a change in surgical procedures from total to subtotal hysterectomies is recommended. PMID- 1592288 TI - Resection of pulmonary metastases from uterine sarcomas. AB - Long-term survival following resection of pulmonary metastases has been well documented. Variables that are believed to have an effect on survival are site of primary tumor, number and size of metastases, resectability, laterality of the metastases, doubling time, and disease-free interval. Published information regarding resection of pulmonary metastases in patients with gynecologic primary tumors is limited. We reviewed 45 patients whose pulmonary metastases from uterine sarcomas were resected at Memorial Sloan Kettering Cancer Center between 1960 and 1989. All cases met carefully defined criteria at time of thoracotomy: prior hysterectomy for uterine sarcoma, no extrathoracic tumor, known disease thought to be resectable, histology consistent with uterine sarcoma, and no medical contraindication to thoracotomy. Seventy-one percent had unilateral lesions, fifty-one percent had one lesion, and seventy percent had nodules greater than 2 cm. Thirty-six percent had incomplete resection at thoracotomy. Actuarial 5- and 10-year survival from hysterectomy for uterine sarcoma was 65 and 50%, respectively, with a mean follow-up of 89 months. Five- and ten-year survival from resection of pulmonary metastases was 43 and 35%, respectively, with a mean follow-up of 25 months. Unilateral vs bilateral disease was a significant predictor of survival after pulmonary resection (P = 0.02). Metastases size, number of metastases, disease-free interval, and patient age were not significant. Among this carefully selected group of patients undergoing resection of pulmonary metastases from uterine sarcomas, long-term survival was achieved by a substantial proportion of patients. No single risk factor is sufficiently accurate to exclude an individual patient from consideration for pulmonary resection. PMID- 1592289 TI - Ovarian carcinoma preceded by cerebral metastasis: review of the literature. AB - A patient with an asymptomatic primary ovarian carcinoma preceded several months before by a solitary intracranial metastasis is reported. The rarity of this phenomenon, the therapeutic experience in this patient, and the possible mechanism of spread are discussed. Also, a review of the literature is made. PMID- 1592290 TI - Metastatic cervical carcinoma to the breast. AB - Metastatic disease to the breast is often an unexpected diagnosis in a female who presents with a breast mass. The most important factor suggesting the appropriate diagnosis is a history of cancer. Correlation of mammographic and ultrasonographic findings may also raise the possibility of a metastatic mass. A well-defined, noncalcified dense mass on film-screen mammography, which also shows low-level homogeneous echoes without posterior acoustic enhancement, suggests the diagnosis. It is important that the diagnosis be made by fine needle aspiration or excisional biopsy so as to expedite appropriate therapy. PMID- 1592291 TI - Squamous cell carcinoma of the endometrium presenting as peritonitis with small bowel obstruction. AB - Squamous carcinoma primary in the endometrium has been rarely reported. Diagnosis of this condition requires adherence to strict histologic criteria. Most patients are postmenopausal at presentation, and long-term survival is poor. We present a patient with peritonitis and small bowel obstruction. Chemotherapy was given after disease recurrence and was ineffective. Receptor data and serum markers were obtained. PMID- 1592292 TI - Ovarian borderline mucinous tumor in a premenarchal girl: review on ovarian epithelial cancer in young girls. AB - Ovarian tumors constitute the most common gynecological neoplasms during childhood. Unlike in adult women, ovarian epithelial tumors are uncommon in young girls and extremely rare prior to menarche. To our knowledge this is the first report of a borderline malignant mucinous tumor of the ovary in a premenarchal girl. It was successfully treated by conservative surgery. In our review of ovarian neoplasms in girls under 20 years of age, epithelial tumors were found in 19.3%, with a malignancy rate of 15.9%. Of these malignant tumors, 39.4% were of the mucinous type and 30.3% were borderline malignant. The occurrence of such a tumor at this age underscores the possibility of malignant transformation of the ovarian epithelium even prior to menarche. Its mucinous nature confirms the predominance of the mucinous subgroup in young girls. Hypotheses on the origin of mucinous tumors are discussed. PMID- 1592293 TI - Endometrioid carcinoma of the ovary presenting with an enlarged inguinal lymph node without evidence of abdominal carcinomatosis. AB - It is generally recognized that ovarian cancer tends to remain intraabdominal even in advanced cases and that dissemination is usually by invasion of adjacent viscera, diffuse intraperitoneal implantation, and metastatic involvement of aortic and pelvic lymph nodes. Primary ovarian lymphatic drainage occurs via the infundibulopelvic ligament to the paraaortic nodes. The presence of an ovarian tumor extending into adjacent pelvic viscera may allow direct lymphatic continuity with inguinal, external, and common iliac lymph nodes. In the absence of such extension it is traditionally believed that the drainage via the infundibulopelvics is so important that only with its blockage, presumably by tumor emboli, can retrograde drainage to pelvic and inguinal nodes occur. We report a case of a patient presenting with a large metastatic inguinal lymph node from a primary epithelial ovarian cancer without evidence of disseminated intraabdominal disease or gross evidence of pelvic or paraaortic lymph node involvement. PMID- 1592294 TI - Malignant transformation of squamous elements within a dermoid cyst. PMID- 1592296 TI - [Congenital arteriovenous facial fistula cured by percutaneous embolization]. AB - Arteriovenous fistulas of the external carotid artery are uncommon. They are usually of traumatic origin but in rare cases may be congenital. When located in regions with difficult access, they constitute a difficult surgical problem because of intra-operative bleeding and significant morbidity. With the advent of transcatheter embolization and new embolic agents, embolization has become the treatment of choice, with a cure rate of over 95%, low morbidity and brief hospitalization. Occlusion of the fistula itself, rather than occlusion of feeding pedicles, is achieved by super-selective catheterization and the use of a suitable permanent embolic agent, depending on location of the fistula and its flow characteristics. A girl aged 2 10/12 with a large, high-flow, arteriovenous fistula of the internal maxillary artery is presented. Complete occlusion of the fistula itself, with full cure, was achieved by super-selective transcatheter embolization using Gianturco coils. There has been no recurrence after more than 7 months of follow-up. PMID- 1592295 TI - [Increased propensity to oxidation of LDL of hypertensives]. AB - Increased incidence of atherosclerosis has been noted in hypertension, but prevention of ischemic heart disease has not been achieved. We studied the propensity to oxidation of LDL obtained from 15 nonsmoking hypertensives (mean age 51 +/- 10) before drug therapy, and compared the results with those of LDL obtained from a similar group of normotensive controls. After oxidation with copper ions (10 microM) there was substantially increased oxidation of LDL derived from the hypertensives in comparison to that of the controls. The mean values (nmol/mg protein +/- SD; n = 15) were: malondialdehyde 55 +/- 11, peroxides 224 +/- 52, and conjugated dienes 250 +/- 56, compared to values of 26 +/- 5, 123 +/- 31 and 175 +/- 44, respectively, in the control group (p less than 0.01). It is concluded that the increased propensity of LDL to oxidation in hypertension may be the link to atherosclerosis. PMID- 1592297 TI - [Dilutional hyponatremia and convulsions after strenuous exercise]. AB - A 15-year-old girl who drank excessive amounts of water while walking in the desert on a warm day, is reported. Due to complaints of fatigue and headache she was treated with more fluids and had a generalized seizure. On admission her sodium level was 125 meq/l and serum muscle enzymes were increased. Hyponatremia due to exertion and dilution is well established and may be more common than thought. It can present as a generalized seizure and with rhabdomyolysis. This case illustrates the danger of overzealous water replacement, especially without adequate replacement of salts. When water discipline is in force this possibility should be considered in patients presenting after prolonged, strenuous exercise or marching. PMID- 1592298 TI - [Adenocarcinoma of the appendix]. AB - Adenocarcinoma of the vermiform appendix is rare. It usually produces signs of acute appendicitis and is discovered only on pathological examination. The treatment of choice is right hemicolectomy, usually performed as a secondary operation. 2 cases of appendiceal carcinoma, in a 59-year-old man and in a 70 year-old woman, are described. PMID- 1592299 TI - [Gastrointestinal lipoma]. AB - During the years 1975-1990 we treated 6 patients, 52-70 years old, with lipomas of the gastrointestinal tract. In 4 cases the diagnosis was made preoperatively. In 5 the tumor was located in the colon and in 1 in the stomach. 4 were treated surgically and 2, with relatively small lesions, were followed for 24 and for 52 months, respectively. A lipoma situated in the alimentary tract may lead to a variety of symptoms. Awareness of this phenomenon and the use of advanced diagnostic modalities may allow definitive clinical diagnosis. PMID- 1592300 TI - [Central venous catheterization via the axillary vein]. AB - Central venous catheterization is a common procedure in the intensive care unit. The vessels usually selected for access include those of the arm and the external and internal jugular, subclavian and femoral veins. We find the axillary vein also suitable. It is a safe and reliable route with few complications, and is especially recommended in ventilated and/or tracheotomized patients. We describe our experience in 80 patients, with a success rate of 90% and very few complications. PMID- 1592301 TI - [Pulmonary siderosis caused by inhalation of iron dust or fumes]. AB - Pulmonary Siderosis results from inhalation of iron dust or fumes. It falls into the group of pneumoconioses in which the pulmonary reaction is minimal despite a heavy dust load. Since fibrosis is not caused by inhalation of iron dust, the clinical course is benign and pulmonary function tests and blood gases are within normal limits. We report the first case of sideropneumoconiosis from Israel, in a 39-year-old iron welder. Since this condition is still not recognized as an occupational disease in Israel, the aim of this presentation is to bring it to appropriate medical attention. PMID- 1592303 TI - [Surfactant replacement--prevention and therapy in respiratory distress syndrome]. PMID- 1592302 TI - [Thrombocytopenia due to glibenclamide]. AB - A 45-year-old male, admitted for severe thrombocytopenia and bleeding tendency related to treatment with glibenclamide is presented. Thrombocytopenic purpura associated with glibenclamide, a short-acting sulfonylurea, is rare. We suggest that platelet counts be performed shortly after initiation of glibenclamide administration, and every 3 months thereafter. PMID- 1592304 TI - [Pathogenesis of pulmonary edema in premature infants]. PMID- 1592305 TI - [Medical uses of artificial cells]. PMID- 1592306 TI - [The nature of functional assessments and their contribution]. PMID- 1592307 TI - [The main issue in terminal dehydration: to give or to withhold fluids?]. PMID- 1592308 TI - [Preventive approach to stroke from the viewpoint of a rehabilitation institution in Israel]. PMID- 1592309 TI - [Long term prognosis following adult respiratory distress syndrome]. PMID- 1592310 TI - [Nutrition and the skin]. PMID- 1592311 TI - [Female circumcision]. PMID- 1592313 TI - [Critical intra-abdominal infections: emerging concepts]. PMID- 1592312 TI - [The myelodysplastic syndrome]. PMID- 1592314 TI - [Effects of chloride ion on the activation of G proteins]. AB - G proteins act as signal transducers that couple receptors to effectors through membranes. G proteins are in a GDP-bound form in the basal state, which can interact with receptors. The hormone-bound receptor promotes GDP-GTP exchange of G proteins. The GTP, Mg(2+)-bound G proteins can activate effector molecules, which in turn produce second messengers. The GTP, Mg(2+)-form is converted to the GDP-form by the GTP-hydrolysis activity of G protein alpha-subunits. Cl- ions modulate the GDP-GTP cycle of G proteins. Cl- ions, in the presence of Mg2+, decelerate the receptor-independent spontaneous release of GDP (ca. 6-fold by 100 mM NaCl), which will result in a lowering of the basal level of second messengers. On the other hand, the GTP-hydrolysis activity of G proteins was suppressed by 3-fold with 100 mM NaCl, which will result in keeping the G proteins in an active form for a longer time. In the absence of Mg2+, Cl- ion mimics Mg2+ to convert GTP-bound G proteins to an active form (dissociated form), although the effects are weaker than those of Mg2+. These effects are very different from F-, which is another halogen ion that interacts with G proteins. PMID- 1592315 TI - [Neuronal intracellular chloride ion concentrations and their regulatory mechanisms]. AB - Intracellular chloride ion concentration ([Cl-]i) plays an important role in cellular functions including the control of membrane potential and excitability. In neurons, Cl- equilibrium potential (ECl) is lower or higher than the membrane potential (Em), suggesting that [Cl-]i is lower or higher than that expected from passive distribution. As the mechanisms to control [Cl-]i, active outwardly or inwardly directed Cl- transport systems have been reported. The former includes Na(+)-dependent Cl-/HCO3- exchanger, K+/Cl- cotransporter and ATP-dependent Cl- pump; and the latter includes Na+/K+/2Cl- cotransporter and amino acid-dependent Na+/Cl- cotransporter. In hippocampal pyramidal cells, recent studies using a Cl( )-sensitive fluorescent probe to monitor [Cl-]i revealed the presence of an ATP dependent Cl- pump and a Na+/K+2Cl- cotransporter, and an uneven distribution of [Cl-]i (cell body less than dendrite) and these Cl- transport systems. Intracerebroventricular administration of an inhibitor of the ATP-dependent Cl- pump, ethacrynic acid, induces status epilepticus in mice. Thus, it appears to be necessary to elucidate cellular and molecular mechanisms of Cl- transporters and their control systems for a better understanding of Cl(-)-related functions in neurons. PMID- 1592316 TI - [Age-dependent changes in the adenylate cyclase system of rat ventral prostate]. AB - Changes in beta-adrenoceptors, GTP binding (G) proteins and adenylate cyclase (AC) activity of ventral prostates of rats during aging were studied in these experiments. The density of beta-adrenoceptors increased markedly after birth, reaching a maximum in the tissues at 16 weeks of age and remained at this level for about 90 weeks. When stimulated by isoproterenol, the AC activity increased 4 and 22-fold in 2- and 8-week-old rats, respectively, but only 7-fold in both 16- and 104-week-old rats. Activation of AC by forskolin was the greatest during the 2 weeks after birth and then showed a sharp decrease, reaching a plateau in the tissues at 8 weeks. Bmax value of [35S]GTP gamma S binding to the tissues was the largest at 8 weeks. Pretreatment of the tissues with pertussis or cholera toxin caused age-dependent changes in both the binding abilities of Gi and Gs proteins to GTP that coincided with changes in the binding of G proteins to GTP. There was no difference between the abilities of Gi and Gs proteins to bind to GTP in the tissues of rats of the respective age. These results show that changes in the binding ability of G proteins to GTP influence the function of ventral prostates of rats during the aging process, and this is mediated through the regulation of AC activity. PMID- 1592317 TI - [Studies on the healing promoting action of Z-103 in chronic gastric ulcer models of rats]. AB - We studied the healing promoting action of Z-103 on the chronic gastric ulcer induced by acetic acid (AAU) or Fe-ascorbic acid (FAU) in rats. The area of the gastric ulcers, hydroxyproline (Hyp) and DNA contents in the ulcer region were measured as an index of ulcer healing. The area of gastric ulcers was the largest on day 4 and thereafter gradually decreased, but the ulcers still remained at the 14th day. Hyp contents in the ulcer region decreased until the 7th day in both models, and then this level increased. Significant decrease in DNA contents in the ulcer region was observed on the 7th day only in FAU. In AAU and FAU, administration of Z-103 (3 mg/kg/day x 2, p.o.) resulted in a significant decrease in the area of gastric ulcers on the 14th day and a significant increase in Hyp contents in the ulcer region on the 7th day as compared with the control group. Z-103 increased the DNA contents in the ulcer region on the 4th day in AAU and on the 7th day in FAU. These results suggest that tissue destruction surrounding the ulcer region in AAU and FAU models might occur until the 4th or 7th day after operation, and that the acceleration of ulcer healing by Z-103 on these models may be facilitated by the wound healing action of this drug. PMID- 1592318 TI - [Effects of adrenergic drugs injected into the nucleus tractus solitarius region on the baroreceptor reflex in rabbits]. AB - It has been presumed that a primary site of termination of the baroreceptor afferent was in the nucleus tractus solitarii (NTS). The intermediate region of the nucleus, located at the level of the obex, contains a large number of catecholamine neurons. The principal noradrenergic innervation of the NTS appears to arise from neurons of the so-called A2 group. It has been proposed that catecholamines released by A2 neurons serve to lower blood pressure and heart rate. We performed experiments to determine the effects of alpha-adrenoceptor agonists and antagonists on the baroreceptor reflex and alpha-adrenoceptor. Rabbits anesthetized with chloralose-urethane were injected with an alpha adrenoceptor agonist, such as noradrenaline, phenylephrine or clonidine, into the NTS. An adrenoceptor-antagonist, such as yohimbine, phentolamine, prazosin or corynanthine was injected into the NTS of other anesthetized rabbits. Clonidine markedly lowered the blood pressure and heart rate, and it inhibited the baroreceptor reflex responses. Noradrenaline or phenylephrine did not lower the blood pressure and heart rate and scarcely inhibited the baroreceptor reflex. Yohimbine remarkedly inhibited the baroreceptor reflex responses; on the other hand, prazosin, corynanthine and phentolamine produced little inhibition of the responses. It is concluded that there are alpha 1- and alpha 2-receptors in the NTS of the rabbits, and the alpha 2-receptors play an important role in the neurotransmission in the NTS. PMID- 1592319 TI - [Suppressive effect of sialic acid on the prostaglandin E2-mediated edema in carrageenin-induced inflammation of rat hind paws]. AB - We performed these studies to determine whether sialic acid (SIA) existed in the inflammatory exudate of the carrageenin (Car)-air pouch model and to elucidate the mechanisms of the antiinflammatory action of SIA on the Car-induced edema in rat hind paws. SIA (113.20 +/- 10.73 micrograms/ml) was detected in the exudate of Car-air pouch, and the plasma SIA (660.29 +/- 29.38 micrograms/ml) in Car-air pouch rats was significantly higher than that (490.00 +/- 29.37 micrograms/ml) in control rats. SIA (300 mg/kg, s.c.) suppressed the delayed phase of Car-induced edema, and it also suppressed the edema induced by Car plus arachidonic acid, Car plus PGE2, and bradykinin plus PGE2. However, SIA did not affect the edema induced by dextran, histamine, bradykinin, and Car plus PGE1. SIA affected neither the PG production in rats nor the [3H]PGE2-receptor binding of guinea pig ileum, and SIA reduced the PGE2-induced contraction of isolated guinea pig ileum. The above results suggest that SIA induces the antiinflammatory effects via its antagonism against PGE2. Furthermore, the presence of SIA in the inflammatory exudate and the higher concentration of SIA in the plasma than in the exudate might suggest that SIA plays patho-physiologically protective roles in inflammatory states. PMID- 1592320 TI - [The effect of L-NG-nitro arginine on non-adrenergic, non-cholinergic (NANC) relaxations in the longitudinal muscle of the guinea pig proximal colon]. AB - We have investigated the effect of the NO synthesis inhibitor L-NG-nitro arginine (L-NNA) on the NANC relaxation induced by electrical field stimulation (FS) or the 5-HT1-like receptor agonist 5-carboxamidotryptamine (5-CT) in the longitudinal muscle of the guinea pig proximal colon. In the presence of atropine (0.2 microM) and guanethidine (5.0 microM), NANC relaxations induced by FS (0.1 10 Hz, 160 mA, 0.3 ms) or 5-CT (1.0-30 microM) were completely abolished by tetrodotoxin (0.3 microM). L-NNA (10-100 microM) produced concentration-dependent inhibition of NANC relaxations, but D-NNA had no effect. This inhibitory effect of L-NNA on NANC relaxations was prevented by L-arginine (1 mM) or L-citrulline (1 mM), but was not affected by D-arginine (1 mM). Like L-NNA, L-NMMA (100-300 microM) also inhibited the NANC relaxation induced by FS and 5-CT. These results suggest that nitric oxide (NO) or a substance releasing NO may contribute to NANC relaxations of guinea pig proximal colon induced by FS and the stimulation of 5 HT1-like receptors. PMID- 1592321 TI - The use of a packed column for the determination of bupivacaine in human plasma by gas chromatography: an application in a pharmacokinetic study of bupivacaine. AB - The method involves a single extraction of the drug and the internal standard, etidocaine, from alkalinized plasma with n-hexane. The gas chromatograph is equipped with a glass column (2.0 m x 2 mm) packed with 3% W/W SP2250 on Chromosorb W, (80/100 mesh) and a nitrogen sensitive detector. The method can accurately measure plasma bupivacaine concentrations down to 0.01 micrograms ml-1 using a sample size of 0.5 ml. The day-to-day variation of bupivacaine at 2.0 micrograms ml-1 is 6.90% (n = 10). The calibration graph is linear over the range 0.1-4.0 micrograms ml-1. The method is accurate, fast and sensitive and has been applied in a pharmacokinetic study of bupivacaine. PMID- 1592322 TI - A more sensitive modification of the zinc test for seminal traces suitable for stable test paper strips. AB - A more sensitive modification of the zinc test for semen has been developed, which can be used either as a solution or incorporated into test papers. The latter retain their sensitivity for at least 3 months. PMID- 1592323 TI - Evaluation of the modified zinc test and the acid phosphatase test as preliminary screening methods in sexual assault case material. AB - The modified zinc test and a commercially available acid phosphatase test were compared as to their screening parameters according to the microscopical finding of spermatozoa in cases of alleged sexual assault. The study involved 65 pieces of evidence material. It was found that the modified zinc test has a higher sensitivity and higher predictive values than the acid phosphatase test. However, when both tests are combined in parallel, the sensitivity and the negative predictive value could be raised to 99%. This finding suggests that a negative result obtained from the parallel combination of the modified zinc test and the acid phosphatase test predicts very well that no spermatozoa will be found at microscopical examination. Since the latter technique is the only one to give absolute proof of the seminal origin of stains or traces, the parallel combination of the zinc test and the acid phosphatase test might be useful in sorting out these cases or materials that deserve further investigation by more elaborate techniques. PMID- 1592324 TI - Toxicological findings in military aircraft fatalities from 1986-1990. AB - Toxicological findings in all military aircraft fatalities investigated by the Division of Forensic Toxicology at the Armed Forces Institute of Pathology from 1986-1990 are presented. Carbon monoxide saturation levels greater than 10% were found in 4% of the 535 cases where appropriate specimens were collected. Positive ethanol findings were more indicative of postmortem formation than antemortem consumption. In only 1 case were abused drugs (cannabinoids in a passenger) detected. Other drugs identified included nicotine, chloroquine and over-the counter analgesic agents, antihistamines and sympathomimetic drugs. PMID- 1592325 TI - A study on the diagnosis of drowning by examination of lung chlorophyll(a) of planktons with a spectrofluorophotometer. AB - An investigation on the diagnosis of drowning by analysis of chlorophyll(a) (Chl.(a)) of planktons in the lung sample with a spectrofluorophotometer (SFPM) is reported. The diagnostic criteria or main points of death by drowning are suggested are according to our experimental studies. Meanwhile two cases of submersion in water were investigated and the causes of death were diagnosed correctly. It is concluded that examination of lung Chl.(a) of planktons could be used as a reliable diagnostic method in forensic practice. PMID- 1592326 TI - Rapid and sensitive typing of forensic stains by PCR amplification of polymorphic simple repeat sequences in case work. AB - After failure of conventional typing and multilocus DNA fingerprinting methods to compare a minute vaginal swab stain with blood from a murder victim and a suspect, we used enzymatic DNA amplification (polymerase chain reaction, PCR) to discriminate the DNAs by typing of simple sequence lengths polymorphisms. A mixed dinucleotide locus in the HLA-DRB gene region and three novel tetranucleotide polymorphisms located autosomally as well as on the human Y chromosome were used to exclude a jailed subject from a case of murder. PMID- 1592327 TI - Investigation of the between-gel and within-gel variation in fragment size determinations found when using single locus DNA probes. AB - Measurement variation in the sizing of DNA fragments has been assessed, examining within-gel and between-gel variability. Also, measurement variation detected between two different laboratories, using both manual and automated measurement techniques, has been investigated and discussed. PMID- 1592328 TI - Determination of fetal age by immunohistochemical estimation of surfactant producing alveolar type II cells. AB - We monitored the immunohistochemically determined amount of surfactant-producing alveolar type II cells in human fetal lung using polyclonal antibodies against apoprotein B and C of human pulmonary surfactant. Lungs of 30 dead-born fetuses without lung affection aged between 15 and 38 weeks of gestation were evaluated and the surface density of surfactant-producing alveolar type II cells was determined by morphometry. In lungs of fetuses with a gestational age less than 22 weeks no relevant number of positively reacting cells could be found. Between the 22nd and 29th week a progressive increase with considerable inter-individual variability was observed. From the 30th week on the number of the type II pneumocytes appeared rather constant without further significant increase. We provide evidence that the immunohistochemical detection of surfactant-producing alveolar type II cells is useful for the determination of the age of unknown and especially fragmented fetuses: The lack of surfactant-producing alveolar type II cells in fetal lungs before the 22nd week allows a rather safe distinction between fetal lungs of higher age from those of lesser age. Between the 22nd and 29th week an age-dependent increase in the number of these cells occurs with wide inter-individual variability allowing only an approximate age determination. In particular, this may be an important piece of information in fragmented fetal corpses. Furthermore, the number of surfactant-producing alveolar type II cells provides additional information on pulmonary maturation and may thus be helpful in the estimation of a theoretical survival chance. PMID- 1592329 TI - Localization and quantification of the nonspecific esterase in injured skin for timing of wounds. AB - Histochemical quantification of the nonspecific esterase (NSE) in injured skin was performed using histochemical demonstration of the enzyme and a microspectrophotometric scanning technique on specimens taken from 32 Hartley guinea-pigs and 8 cases of human skin wounds. In all antemortem incisions and lacerations, including those made at the agonal stage, NSE activity could be observed in the dermal tissue of the wound edge. The enzyme activity increases with the antemortem duration of the injuries. Both total content and mean concentration of NSE in the wound edge between antemortem and postmortem wound groups differ significantly (less than 0.01). Multiple range test shows that significant differences (P less than 0.05 or P less than 0.01) of total content of NSE in the wound edge also exist in 0-5 min, 15-30 min, 1-h, 2-h and 4-h antemortem incised wound groups and in 0-min, 5-min, 15-30 min, 1-h and 4-h antemortem laceration groups. The positive NSE reactions in 8 cases of human skin wounds were similar. The study indicates that histochemical quantification of NSE in injured skin is very useful in timing wounds and is exactly applicable in medicolegal practice. According to the different influences of inhibitors on enzymes, it was inferred that the enzyme activity in wound edges was due to B esterase. PMID- 1592330 TI - Determination of cocaine and its metabolites in brain tissue using high-flow solid-phase extraction columns and high-performance liquid chromatography. AB - A new solid-phase extraction procedure for the determination of cocaine and some of its metabolites in brain tissue, using high-flow co-polymeric sorbents is reported as a substantial improvement on our recently reported procedure. The recovery of cocaine, norcocaine and cocaethylene was excellent as was the reproducibility of the extraction. The use of high-flow sorbents allowed the easy extraction of tissue without the need for a time-consuming lipase digestion, regardless of sample viscosity or physical nature. The use of these solid-phase columns provided many advantages over the more commonly used solvent extraction, including an increase in extraction speed and efficiency, reduced operator time, reduced solvent use and disposal volumes and exceptional extract quality. The procedure was successfully applied to rabbit brains spiked with cocaine, benzoylecgonine, norcocaine and cocaethylene. PMID- 1592331 TI - Drugs and alcohol consumption amongst Spanish drivers. AB - We have analysed patterns of alcohol and regular drug consumption by Spanish drivers. Six hundred and seventy five properly completed questionnaires were received from drivers attending three medical traffic centres in Valladolid (Spain) for medical examination prior to obtaining or renewing their driving licence in 1990. Among those surveyed, 24% were 'daily' drinkers and 56.7% were 'weekly' drinkers, the majority (55.5%) being 'light' drinkers (1-39 g/day of pure alcohol). Of those surveyed 28.9% took drugs. The most commonly consumed drugs were analgesics (6.5%), anti-allergic drugs (5.2%) and oral contraceptives (4.6%). Of those drivers taking drugs 28.2% were 'daily' drinkers and 53.8% were 'weekly' drinkers. The study indicates widespread consumption of alcohol and drugs by Spanish drivers. PMID- 1592332 TI - [A case of the diabetic nephropathy without hyperglycemia]. AB - We report a case of diabetic nephropathy with impaired glucose tolerance. A 52 year obese woman with nephrotic syndrome and hypertension showed severe and remarkable edema, as her legs were elephantiasis. To be clear the etiology of nephrotic syndrome, we performed renal biopsy. The histological findings of the specimen showed glomerulosclerosis. Additionally the examination of ocular fundus revealed microaneurysm and avascular area. We concluded that diagnosis of this case must be non-insulin-dependent diabetes mellitus. PMID- 1592333 TI - [Five cases of Crow-Fukase syndrome]. AB - We presented five cases of Crow-Fukase syndrome. Plasma cell hyperplasia or dyscrasia in bone marrow were recognized in all cases and localized bone lesion was seen in three cases. Thyroid dysfunction was seen in three cases; hyperthyroidism in one case and hypothyroidism in two cases, which was considered to be one of the characteristics though it has seldom been described in this disease. Two of four cases treated with prednisolone had good responses but two cases treated with interferon had no effect. PMID- 1592334 TI - [Epidemiology of influenza]. PMID- 1592335 TI - Long-term follow-up of cardiac rhythms after biatrial transseptal approach (Dubost's incision). AB - Biatrial transseptal approach (Dubost's incision) was performed 54 times on 47 patients from November 1973 to December 1982 at National Fukuoka Higashi Hospital in Japan. The patients consisted of 19 males and 28 females, with ages ranging from 14 to 66 (mean 45.9 years). Forty-four out of 47 cases had rheumatic heart disease while one had endocardial cushion defect, one had Lutembacher's syndrome, and one had left atrial myxoma. Preoperative electrocardiograph showed atrial fibrillation in 37 cases (78.7%) and normal sinus rhythm in 10 cases (21.3%). The follow-ups of the patients were a minimum of 8 years and a maximum of 16 years (mean 9.6 years) with 97.8% completion. Cumulative follow-up period was 448.9 patient years. Postoperatively, atrial fibrillation persisted in all except two. In those patients, normal sinus rhythm was observed until postoperative six months and seven years, respectively. Normal sinus rhythm persisted in six cases, and changed into junctional rhythm in four. One of them changed into atrial fibrillation at 10.6 years postoperatively. We conclude that Dubost's incision provides an excellent operative field for mitral and tricuspid valve surgery without serious internodal conduction disturbances. PMID- 1592336 TI - [Upper gastrointestinal endoscopic findings and gastric mucosal blood flow in patients with rheumatoid arthritis]. AB - In order to clarify the mechanism of peptic ulceration complicating rheumatoid arthritis (RA), the endoscopic examination of the stomach and duodenum, and the measurement of gastric mucosal blood flow (GMBF, ml/min/100 g) were performed in 49 patients with RA, in relation to the clinical variables (age, sex, disease duration, anatomical stage, functional class and disease activity) and drugs administered. Most of peptic ulcer (88%, 22/25) was found in the gastric mucosa in RA patients, of which antral ulcer occupied 82% (18/22). GMBF in the antrum was significantly lower in RA patients with antral ulcer than in those with normal gastric findings, while GMBF in the gastric body was rather higher in either patients with antral or other gastric ulcer, especially in patients with the angle or body ulcer. The prevalence of antral ulcer tended to be higher in females than in males, and GMBF in the antrum was significantly lower in the former than in the latter (42.7 +/- 11.0 vs 55.6 +/- 12.6). There was no relationship between the prevalence of antral ulcer or GMBF and the activity of RA. All the patients except 4 had received non-steroidal anti-inflammatory drugs (NSAIDs), and of these 45 patients, 24 had also steroids. The prevalence of antral ulcer was higher in patients taking NSAIDs and steroids more than 5mg prednisolone concomitantly than in those taking NSAIDs only, although there was no difference in GMBF in the antrum between them. The prevalence of antral ulcer in patients taking NSAIDs, according to the kind of NSAIDs taken, was the highest in phenylacetic acids group. The difference was significant between propionic acids group and phenylacetic acids group. GMBF in the antrum of phenylacetic acids group was the lowest among the three groups (34.7 +/- 7.1 in phenylacetic acids, 46.6 +/- 11.2 in oxicams and 47.7 +/- 12.6 in propionic acids). Those results indicate that long-term administration of NSAIDs may selectively inhibit GMBF in the antrum, leading to impairment of the protective mechanism in the gastric wall and subsequent occurrence of antral ulcer. PMID- 1592337 TI - [A study on pathogenesis of gastric mucosal lesions in hemodialysis patients, with special reference to the gastric mucosal blood flow]. AB - Clinical characteristics of gastric mucosal lesions in hemodialysis patients were studied. The relationships between the occurrence of gastric mucosal lesions and changes of gastric mucosal blood flow were studied in normal subjects and hemodialysis patients to clarify causes of gastric mucosal lesions in them. Erosive gastritis, gastric ulcers and hemorrhagic gastritis were the main manifestations of the lesions in hemodialysis patients. The lesions were mainly localized in the gastric antrum. Hemorrhagic gastritis lesions were also found in the gastric body as well as in the gastric antrum. The gastric mucosal blood flow in the gastric body showed lower values than in healthy controls while gastric mucosal blood flow in the antrum revealed no such significant difference. Therefore, it can be considered that the low value of gastric mucosal blood flow in the gastric body may contribute to the occurrence of gastric mucosal lesions in the gastric body in hemodialysis patients. However, gastric mucosal lesions in hemodialysis patients were localized mainly in the gastric antrum, and, accordingly, the changes in the gastric mucosal blood flow are not supposed to account for the lesions in the gastric antrum. Further studies are, therefore, required to clarify the causes of gastric mucosal lesions in hemodialysis patients. PMID- 1592338 TI - Absence of hepatitis B virus precore mutants in patients with chronic hepatitis B responding to interferon-alpha. AB - Precore defective HBV mutants may gradually prevail because of immune selection and explain spontaneous seroconversion from HBeAg to anti-HBe in HBV carriers. We have analyzed whether the presence of precore HBV mutants is a determinant of responsiveness to interferon-alpha therapy. Fifteen carriers (nine responders and six nonresponders) who were treated with interferon-alpha were examined. Serum samples were collected before and after therapy. After extraction of DNA, the precore region was amplified by the polymerase chain reaction, and the product was identified by gel electrophoresis and ethidium bromide staining and then Southern blotting and molecular hybridization. The amplified products in all patients were asymmetrically amplified by a modified polymerase chain reaction, and the precore region was directly sequenced. All patients were HBV DNA positive initially. Circulating HBeAg-negative mutants were not identified before treatment in either responders or nonresponders. All nine responders were negative for HBV DNA in serum by dot blot during or after treatment, but seven remained positive by polymerase chain amplification and Southern-blot hybridization. All of the nonresponders remained positive for HBV DNA by dot blot. A silent mutation involving the substitution of an A for G at position 1888 was found in seven carriers; however, no HBeAg-negative mutants were detected in the follow-up of either responders or nonresponders to interferon-alpha.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592339 TI - Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase activities: implication in alcoholic cirrhosis in white patients. The French Group for Research on Alcohol and Liver. AB - Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis. PMID- 1592340 TI - Bleeding from staple line erosion after esophageal transection: effect of omeprazole. AB - Esophageal staple transection effectively controls acute variceal bleeding, but up to 50% of these patients will have recurrent upper gastrointestinal bleeding. In our experience, most of these bleeding episodes are caused by total or partial circumferential ulceration at the level of the staple transection: staple line erosion. It caused rebleeding in 29 (40%) of our patients. Whereas the pathogenesis of this lesion is unknown, acid reflux is a consequence of transection surgery. Assuming that staple line erosion could be healed by acid suppression therapy, thereby preventing recurrent bleeding, an acid suppression regimen was evaluated prospectively in 24 patients. Only six (25%) healed with daily standard (300 mg) or high-dose (1,200 mg) ranitidine combined with sucralfate (4 gm). The remaining 18 (75%) healed after omeprazole administration (40 mg/day) for 1 mo. Maintenance ranitidine alone (300 mg/day) was introduced, but 11 (48%) had relapse of erosions. All 11 healed with omeprazole (40 mg/day) for 2 mo, but again on maintenance ranitidine, 10 relapsed. All healed with further omeprazole and healing persisted with long-term administration (20 mg/day). Fifteen rebleeding episodes occurred in eight patients on maintenance ranitidine. Whereas relapse of staple line erosions did occur in the absence of rebleeding, all rebleeding episodes were associated with the relapse of staple line erosion. Omeprazole is more effective than ranitidine alone and combined with sucralfate in healing staple line erosion. Omeprazole prevents rebleeding, which may enhance the long-term benefits of staple transection for acute variceal bleeding. PMID- 1592341 TI - Transjugular liver biopsy in children. AB - Transjugular liver biopsy is widely used in adult patients with liver disease when transthoracic needle liver biopsy is contraindicated by severe coagulopathy or ascites. It has not been used extensively in children. We report our experience with 30 consecutive transjugular liver biopsy procedures performed in 27 young patients at the Hospital for Sick Children in Toronto. Patient weights ranged from 14 to 91 kg (median = 42 kg); most patients had not yet attained adult size. A 9F catheter was used except in very small children, for whom we developed a 7F biopsy needle catheter. Most procedures were done with patients under general anesthesia. Specimens were obtained in all patients, and the procedure was tolerated well. A major complication occurred only once: perforation of the inferior vena cava, which was later repaired at liver transplantation. Minor complications included subcapsular extravasation of contrast agent in five patients and a small intrahepatic hematoma in one. Results of transjugular liver biopsy changed the diagnosis in 30% of patients and added valuable information about the disease process in most patients. Transjugular liver biopsy was an important component of emergency assessment for liver transplantation. Our results indicate that transjugular liver biopsy can be performed safely in children with liver disease if a skilled interventional radiologist and a well-equipped angiography suite are available. Histological studies in these patients enhance our understanding of the natural history of pediatric liver diseases. PMID- 1592342 TI - Effects of ursodeoxycholic acid in patients with intrahepatic cholestasis of pregnancy. AB - The efficacy and safety of ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy was investigated in an open pilot study. Five patients received 1 gm/day of ursodeoxycholic acid during 20 days and another three patients received two identical periods of treatment separated by a 14-day interval free of the drug. Pruritus and serum levels of total bile salts and glutamic-pyruvic transaminase improved significantly during treatment with ursodeoxycholic acid. In the three patients who received two periods of treatment with ursodeoxycholic acid, pruritus and the laboratory alterations relapsed in the second week after the drug was discontinued, but they improved again when ursodeoxycholic acid was readministered. No adverse reactions were detected in the mothers or in their babies. All newborns were thriving normally during a follow-up period that lasted 5 mo after delivery. It is concluded that UDCA appears to be safe when administered in late pregnancy; its promising efficacy in the treatment of intrahepatic cholestasis of pregnancy should now be confirmed in controlled clinical trials. PMID- 1592343 TI - Hemodynamic and liver function predictors of serum hyaluronan in alcoholic liver disease. AB - To define hepatic predictors of serum hyaluronan in patients with chronic liver disease, 62 patients with alcoholic liver disease were evaluated. In group 1, 30 patients had concurrent assessment of serum hyaluronan, liver function tests, Pugh grade and hemodynamic indices. A second, overlapping group of 42 patients (group 2) also had antipyrine clearance measured but without hemodynamic assessment. All but six patients had elevated serum hyaluronan levels. In both groups, serum hyaluronan levels differed between Pugh grades and, in each group, was significantly greater in Pugh grade C compared with those in Pugh grade A (p less than 0.05, Kruskal-Wallis test). When analyzed by correlation, serum hyaluronan was significantly associated with several indices in group 1, but on multivariate linear regression only three statistically independent predictors of serum hyaluronan were identified: serum albumin (p = 0.008), indocyanine green clearance (p = 0.024) and indocyanine green extraction (p = 0.036). The overall R2 for these correlates was 65%. In the second group, antipyrine clearance was not significantly associated with serum hyaluronan (r = 0.29, p = 0.06), but other associations were similar to the first group. On multivariate analysis, only serum albumin predicted serum hyaluronan (p less than 0.001; R2 = 43%). In conclusion, indices of hepatocyte synthetic function, sinusoidal blood flow and degree of intrahepatic shunting are independent predictors of serum hyaluronan in alcoholic liver disease. These data show the unique nature of serum hyaluronan and suggest its potential application to the assessment of acute hemodynamic changes in patients with liver disease. PMID- 1592344 TI - Electron microscopic study of brain capillaries in cerebral edema from fulminant hepatic failure. AB - Cerebral edema is a serious complication of the encephalopathy in fulminant hepatic failure. It is a major cause of death. The mechanisms responsible for its formation are unclear, and the aim of this study was to investigate the ultrastructural appearance of brain capillaries by scanning electron microscopy. Samples of cerebral cortex were obtained immediately after death from nine patients with fulminant hepatic failure (seven cases due to acetaminophen overdose, one caused by hepatitis B and one caused by non-A, non-B hepatitis) by needle biopsy at the site of insertion of an extradural pressure transducer to monitor intracranial pressure. The intercellular tight junctions between capillary endothelial cells were intact. The endothelial cells were swollen, with increased numbers of vesicles and vacuoles. The basement membranes were enlarged and vacuolized and the pericytes had increased numbers of vesicles and vacuoles, indicative of passage of fluid by this route. Marked intracellular swelling of the perivascular astroglial foot processes was present. Thus mainly cytotoxic mechanisms, with cellular swelling, and to a lesser extent vasogenic mechanisms, with altered blood-brain barrier permeability, appear to be involved in the cerebral edema of fulminant hepatic failure. PMID- 1592345 TI - Effects of vasopressor agents and epoprostenol on systemic hemodynamics and oxygen transport in fulminant hepatic failure. AB - Hypotension is a serious complication in patients with fulminant hepatic failure, because it is associated with tissue hypoxia and a further compromise to end organ function. In this study we investigated the effects of epinephrine and norepinephrine on hemodynamics and oxygen transport variables in 30 patients with fulminant hepatic failure. All had a mean arterial pressure of less than 60 mm Hg, despite adequate intravascular filling pressures. Both epinephrine (n = 15) and norepinephrine (n = 15) improved mean arterial pressure (p less than 0.001 epinephrine and norepinephrine), although this was not associated with a rise in oxygen delivery. Oxygen consumption fell (p less than 0.05 epinephrine, p less than 0.001 norepinephrine) because of a lower oxygen extraction ratio (p less than 0.01 epinephrine and norepinephrine). The addition of epoprostenol, a microcirculatory vasodilator, in 10 patients from each group led to an increase in oxygen consumption (p less than 0.001 epinephrine and norepinephrine) because of a rise in oxygen delivery (p less than 0.05 epinephrine, p less than 0.01 norepinephrine) and oxygen extraction ratio (p less than 0.01 epinephrine, p less than 0.001 norepinephrine), without a fall in mean arterial pressure. The fall in oxygen consumption after the institution of vasopressor therapy could exacerbate tissue hypoxia and thus contribute to further organ damage in an already susceptible patient. In patients with fulminant hepatic failure who are given vasopressor support, the addition of epoprostenol may prevent the development of tissue hypoxia. PMID- 1592346 TI - Effect of simvastatin, ursodeoxycholic acid and simvastatin plus ursodeoxycholic acid on biliary lipid secretion and cholic acid kinetics in nonfamilial hypercholesterolemia. AB - It has been recently shown that the newest hypocholesterolemic agent, simvastatin, lowers the biliary cholesterol saturation index and that its association with ursodeoxycholic acid renders it more effective. To determine the mechanism by which simvastatin decreases the biliary cholesterol saturation index, we evaluated hepatic secretion rates of cholesterol, bile acids and phospholipids, and cholic acid pool size, turnover and synthesis in eight hyperlipidemic patients (five women and three men, age range = 38 to 65 yr). These assessments were conducted before treatment, after 4 wk of simvastatin (40 mg/day), after 4 wk of ursodeoxycholic acid (600 mg/day) and after a further 4 wk of a combination therapy of simvastatin (40 mg/day) plus ursodeoxycholic acid (600 mg/day). The cholesterol saturation index was significantly reduced with simvastatin (from 1.51 +/- 0.10 to 0.94 +/- 0.05, mean +/- S.E.; p less than 0.02), with ursodeoxycholic acid (from 1.51 +/- 0.10 to 0.86 +/- 0.03, mean +/- S.E.; p less than 0.02) and with the combination of simvastatin plus ursodeoxycholic acid (from 1.51 +/- 0.01 to 0.70 +/- 0.05, p less than 0.02). The cholesterol saturation index during combination therapy was significantly lower (p less than 0.02) than that reached during the use of simvastatin and ursodeoxycholic acid. Both simvastatin and ursodeoxycholic acid significantly reduced the hepatic secretion rate of cholesterol (from 130 +/- 14 mumols/hr to 81 +/- 12 mumols/hr, p less than 0.01, and 70 +/- 9 mumols/hr, p less than 0.01) without affecting bile acid and phospholipid outputs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592347 TI - Isolation of a calcium-regulatory protein from black pigment gallstones: similarity with a protein from cholesterol gallstones. AB - We have previously isolated from 13 cholesterol gallstones a low molecular weight acidic bili-protein that inhibited the precipitation of calcium carbonate in vitro. We now report the isolation of a similar protein from seven black pigment gallstones. Cholesterol was removed from the stones by Soxhlet apparatus with methyl t-butyl ether, and bile acids were extracted with methanol. The protein was purified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after demineralization of the stones with ethylenediaminetetraacetate. Structural and functional properties of the protein from the black stones that were similar to the protein from the cholesterol stones included the following: (a) an apparent molecular weight of about 5 kD; (b) a high content of acidic (19.8%) and hydrophobic (50.1%) amino acids with a low content of basic residues (8.4%) and little sulfide-containing amino acids (1.9%); (c) an inhibitory effect on both the initiation and growth of calcium carbonate crystals in vitro; and (d) very tight (possibly covalent) binding of a diazo-positive yellow pigment, presumably bilirubin, with maximum spectral absorbance at 410 nm. The structural and functional similarities of these bili-proteins from black pigment and cholesterol gallstones and their striking effects on calcium carbonate precipitation in vitro suggest that they play a common role in the regulation of precipitation of calcium salts during the formation of both types of gallstones. PMID- 1592348 TI - Hepatic allograft cyclosporine concentration is independent of the route of cyclosporine administration and correlates with the occurrence of early cellular rejection. AB - This study compares the hepatic-tissue cyclosporine concentrations in liver biopsy specimens from patients with and without cellular rejection after orthotopic liver transplantation. Nine patients without cellular rejection were studied, including five patients receiving intravenous cyclosporine who had biopsies on posttransplant day 7 and four patients receiving oral cyclosporine who had biopsies on day 21. In these patients no significant differences were seen in blood cyclosporine concentrations (mean +/- S.D.) (310 +/- 162 vs. 273 +/ 310 ng/ml) and hepatic-tissue cyclosporine concentrations (3,451 +/- 1,262 vs. 3,545 +/- 456 ng/gm). These nine patients without cellular rejection were then compared with eight patients with cellular rejection who were receiving intravenous cyclosporine, including seven patients who had biopsies on post transplant day 7 and one patient who had a biopsy on day 14. In patients with and without cellular rejection blood cyclosporine concentrations were 330 +/- 64 vs. 294 +/- 146 ng/ml, and hepatic-tissue cyclosporine concentrations were 1,879 +/- 998 vs. 3,493 +/- 936 ng/gm, p less than 0.01. We conclude that hepatic-tissue cyclosporine concentrations are independent of the route of cyclosporine administration and that low hepatic-tissue cyclosporine concentrations correlate with early cellular rejection after orthotopic liver transplantation. PMID- 1592349 TI - Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content and their significance for the realization of an estrogen effect on angiotensinogen blood level in rats. AB - The use of a modified, adequate method of quantification of estrogen receptors has permitted us to prove the existence of sex-specific peculiarities in rat liver estrogen reception and their significance for the realization of sex dependent changes in angiotensinogen plasma level after estrogenization. Endocrine mechanisms for the formation of sex-related differences in hepatic estrogen receptor content in rats were investigated in detail. The investigation shows that androgens have negative regulatory influence on the hepatic estrogen receptor level in rats. Estrogens and adrenal and thyroid hormones do not take part in the regulation of hepatic estrogen receptor content in rats. It has been proven that the decisive role in keeping up a certain estrogen receptor concentration in hepatocytes belongs to pituitary growth hormone. It was shown for the first time that androgens are able to inhibit the stimulatory effect of growth hormone on hepatic estrogen receptors. PMID- 1592350 TI - Changes of hepatic fatty acid metabolism produced by chronic thioacetamide administration in rats. AB - Hepatic mitochondrial functions related to fatty acid metabolism, including the respiratory control ratio, fatty acid oxidative capacity and carnitine palmitoyltransferase I activity, were studied in vitro with mitochondria isolated from rats treated with thioacetamide for up to 12 wk. The levels of ketone bodies, carnitine, carnitine esters and malonyl-coenzyme A were also determined in liver extracts. Polarography of mitochondrial respiration from succinate or glutamate plus malate showed a lower respiratory control ratio in thioacetamide treated rats, whereas uncoupled oxygen consumption was not altered. This suggests that the mitochondrial respiratory chain capacity remained intact in the thioacetamide-treated rats. The oxygen consumption associated with palmitoyl coenzyme A and palmitoyl-L-carnitine oxidation by isolated liver mitochondria was increased by thioacetamide treatment on both a per-mitochondrial protein and a per-total liver basis. The carnitine palmitoyl-transferase I activity; the tissue levels of ketone bodies, carnitine and carnitine esters; and the beta hydroxybutyrate/acetoacetate ratio were all higher in the livers of thioacetamide treated animals than in control livers, whereas the hepatic malonyl-coenzyme A level was decreased by thioacetamide. These results indicate the increased diversion of cytosolic long-chain acyl-coenzyme As into the mitochondria for beta oxidation rather than their esterification and use in lipogenesis. These intrahepatic metabolic changes induced by chronic thioacetamide administration may reflect the whole-body catabolic state and can be seen as adaptive for maintaining energy homeostasis under conditions of impaired glucose tolerance. PMID- 1592351 TI - Adenosine receptor blockade reduces splanchnic hyperemia in cirrhotic rats. AB - To explore a possible role for adenosine in the pathogenesis of the splanchnic hyperemia of cirrhosis, we administered 8-phenyltheophylline, a specific adenosine receptor antagonist, to rats with biliary cirrhosis caused by bile duct ligation and to control sham-operated rats. Micro-Doppler flow studies showed that a 10-mumol/kg dose of 8-phenyltheophylline completely abolished the superior mesenteric hyperemic response to infusions of exogenous adenosine in both cirrhotic and control rats. Analysis of regional blood flows by radioactive microspheres demonstrated that this dose of 8-phenyltheophylline in cirrhotic rats significantly increased portal tributary vascular resistance by 60% and decreased portal tributary blood flow by 26%. This decrease was entirely the result of a 42% reduction in the intestinal blood flow. 8-phenyltheophylline did not affect cardiac output, arterial pressure or any other extrasplanchnic hemodynamic variables in cirrhotic rats. No detectable effect of 8 phenyltheophylline was seen in sham-operated rats. These results suggest that adenosine may be involved in the genesis of splanchnic hyperemia in cirrhotic rats. PMID- 1592352 TI - Cytokines tumor necrosis factor and interleukin-6 in experimental biliary obstruction in mice. AB - The putative role of the cytokines interleukin-6 and tumor necrosis factor in the pathophysiology of the complications and mortality after surgery in jaundiced patients was studied in a murine model. Cytokine serum levels were determined in mice with experimental biliary obstruction. As an indicator of the activation status of macrophages, cytokine release by mononuclear phagocytes obtained from such mice was assessed. Following surgery, interleukin-6 levels increased to 2 to 3 ng/ml after 3 to 4 hr, but declined rapidly afterward to levels of 60 pg/ml after 10 days. After 12 days, substantial interleukin-6 levels were observed in jaundiced mice (100 pg/ml), whereas levels in sham mice further decreased (p less than 0.001). The cytokine tumor necrosis factor was frequently present in the serum of jaundiced mice. After 22 days, when killed, all jaundiced mice showed significant tumor necrosis factor levels (p less than 0.001). This was in contrast to sham mice in which tumor necrosis factor was never detected. The presence of an activated state of macrophages in jaundiced mice was concluded from the observed high spontaneous cytokine release and significantly higher release after stimulation (p less than 0.05). The presence of circulating cytokines was discussed in the context of the postoperative complications observed in jaundiced patients. PMID- 1592353 TI - Defective biliary excretion of epinephrine metabolites in mutant (TR-) rats: relation to the pathogenesis of black liver in the Dubin-Johnson syndrome and Corriedale sheep with an analogous excretory defect. AB - Dubin-Johnson patients, mutant Corriedale sheep and TR- and EHBR mutant rats have recessively inherited defective bile canalicular secretion of many nonbile acid organic anions. The human and ovine mutants have black livers and lysosomal pigment accumulation. The livers in TR- and EHBR mutant rats are not black, and sparse lysosomal pigment accumulation is seen. Previously, we postulated that the unidentified pigment in the Dubin-Johnson syndrome results from the accumulation of tyrosine, phenylalanine and tryptophan metabolites, such as metanephrine, which are normally secreted in bile as organic anions. We tested this hypothesis in TR- rats. 3H-epinephrine was injected intravenously; control rats secreted 2.80% +/- 0.52% of the injected dose in bile as compared with 0.19% +/- 0.07% in TR- rats. From 82% to 90% of biliary radioactivity was due to polar conjugates in control rats and mutant rats. TR- rats retained more of the injected dose in the liver, particularly in lysosomes, and secreted more in urine than did control rats. After feeding control and TR- rats for 4 mo with a rat chow diet supplemented with 4% tyrosine, tryptophan and phenylalanine, the liver did not become grossly black; however, histological and electron microscopic study revealed dense lysosomal pigment accumulation in TR- rats. Intraportal injection of metanephrine resulted in the appearance of black liver in TR- rats that persisted for at least 2 hr and was not associated with pigment accumulation by light or electron microscopic examination.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592354 TI - Reduced activity of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis. AB - Mitochondrial metabolism was studied in liver mitochondria isolated from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk. State 3 oxidation rates were decreased in mitochondrial preparations from bile duct ligated rats as compared with sham-operated control rats by 63% and 42% using beta-hydroxybutyrate and succinate as substrates, respectively. In contrast, when the substrate was ascorbate/N,N,N',N'-tetramethyl-p-phenylenediamine state 3 oxidation rates were not affected by bile duct ligation. Oxidation rates after uncoupling with dinitrophenol were decreased for both beta-hydroxybutyrate and succinate as substrates in mitochondria from bile duct-ligated rats. The phosphate potential was reduced in mitochondria from bile duct-ligated rats (12.5 +/- 0.5 vs. 13.6 +/- 0.2 kcal in control and bile duct-ligated rats, respectively; p less than 0.05). The inner mitochondrial membrane of liver mitochondria from rats with secondary biliary cirrhosis contained three times more cholesterol as compared with control rats, whereas the phospholipid composition was essentially unchanged. Mitochondrial protein content expressed per liver (calculated on the basis of activities of mitochondrial enzymes determined in liver homogenate and in isolated mitochondria) was increased by 50% in bile duct-ligated rats as compared with control rats. In conclusion, the function of the electron transport chain in liver mitochondria isolated from rats with secondary biliary cirrhosis is impaired. This decrease could be related to altered lipid composition of the inner mitochondrial membrane. PMID- 1592355 TI - Stereological and functional analysis of liver mitochondria from rats with secondary biliary cirrhosis: impaired mitochondrial metabolism and increased mitochondrial content per hepatocyte. AB - Mitochondrial and cytosolic functions were studied in vivo and in perfused livers from rats with secondary biliary cirrhosis induced by bile duct ligation for 5 wk and in sham-operated controls. The livers were stereologically analyzed, and mitochondrial and cytosolic functions were related to liver structure. Oxygen consumption by perfused livers expressed per stereologically determined mitochondrial volume was decreased by 49% in bile duct-ligated rats compared with control rats. Glucose production (expressed per mitochondrial volume) was reduced by more than 90% in bile duct ligation, whereas urea production was not affected. Lactate production, a cytosolic function, was increased fivefold in bile duct ligation, and both the lactate/pyruvate and the beta-hydroxybutyrate/aceto acetate ratios were increased in the liver perfusate of bile duct-ligated rats. In comparison with control rats, the stereologically determined mitochondrial volume fraction per hepatocyte was increased by 28% in bile duct-ligated rats. Activities of mitochondrial enzymes expressed per area of mitochondrial membrane or per mitochondrial volume were either unchanged (ATPase, cytochrome c oxidase and glutamate dehydrogenase) or decreased (monoamine oxidase) in bile duct ligation. Thus in comparison with control rats, mitochondrial metabolism is impaired in perfused livers from bile duct-ligated rats; increased mitochondrial volume per hepatocyte may represent a strategy to maintain hepatic energy metabolism in rats with secondary biliary cirrhosis. PMID- 1592356 TI - Extracellular matrix gradients in the space of Disse: relevance to liver biology. PMID- 1592357 TI - The touch that hepatocytes seem to like. PMID- 1592358 TI - Extracellular matrix regulation of hepatic transcription factors is dependent on cell structure. PMID- 1592359 TI - Role of extracellular matrix in regulating fenestrations of sinusoidal endothelial cells isolated from normal rat liver. AB - Open fenestrations are a conspicuous feature of sinusoidal endothelial cells and allow free movement of plasma into the space of Disse. In hepatic fibrosis, the number of fenestrations decreases as interstitial collagen increases in the liver, a change that correlates with deposition of extracellular matrix in the space of Disse. In this study, the possibility of a causal relationship between altered fenestral morphology and perisinusoidal matrix has been examined by culturing rat sinusoidal endothelial cells on individual matrix proteins or on a native matrix consisting of human amniotic membrane with interstitial collagen (types I and III) on one side and basement membrane proteins (collagen types IV and V and laminin) on the other. Under culture conditions, individual components of the extracellular matrix failed to maintain fenestrations. A basement membranelike gel matrix derived from the Engelbreth-Holm-Swarm tumor war similarly ineffective. Fenestral density and porosity (percentage of cell surface occupied by fenestrations) were significantly enhanced, however, when endothelial cells were cultured on the basement-membrane side of human amnion. These data suggest that support of endothelial fenestrations requires a complex matrix. In particular, physiologically derived basement membrane maintains fenestrations, whereas interstitial collagen matrix does not. The loss of fenestrations associated with hepatic fibrosis may be related in part to an accumulation of interstitial collagens in the space of Disse. PMID- 1592360 TI - Intensive retreatment of adults and children with acute lymphoblastic leukemia. AB - Twenty-three patients (16 adults) failing their first or subsequent (n = 8) intensive treatment for de novo acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia lymphoid blast phase (n = 2) were managed with protocol POG 8201, originally introduced in relapsed ALL of childhood. In this programme, a four-drug induction phase is followed by early consolidation with teniposide cytarabine, intrathecal chemotherapy, continuation weekly chemotherapy alternating teniposide-cytarabine with vincristine-cyclophosphamide, and periodic reinduction courses. Fourteen adults and five children with ALL achieved a complete response (CR) (86 per cent). The highest response rate (100 per cent) was obtained in 12 patients treated at first relapse after an initial CR of greater than 18 months (p = 0.07). Median duration of CR was 8 months in adults and 11 months in children. A longer than previous one CR (inversion) was obtained in four cases. Four ALL patients were successfully transplanted from a matched sibling after 3-11 months from achievement of CR. Median overall survival in adults with ALL was 11 months, significantly longer than for 40 comparable cases treated intensively but without rotational continuation therapy in previous years (p less than 0.001). This regimen is applicable to adults with relapsed ALL, where prolongation of survival may allow time for effective salvage with bone marrow transplantation. PMID- 1592361 TI - Comparative pharmacokinetic study of idarubicin and daunorubicin in leukemia patients. AB - We have studied the pharmacokinetics of idarubicin and daunorubicin in a total of 16 leukemic patients treated with one of these drugs associated with aracytine. The AUCs obtained for unchanged drugs were proportional to the dose, and the dose independent pharmacokinetic parameters were very similar for the two drugs: total plasma clearance (39.0 L/h/m2 for idarubicin versus 38.6 for daunorubicin), total volume of distribution (1756 versus 1725 L/m2) and elimination half-life (42.7 versus 47.4 h). The only metabolites detected were the 13-dihydroderivative of each drug, idarubicinol or daunorubicinol. The elimination half-life of idarubicinol was two times higher than that of daunorubicinol (80.7 versus 37.3 h) which provided an AUC ratio metabolite/parent drug higher for idarubicin than for daunorubicin. In view of the fact that idarubicinol is a much more active metabolite than daunorubicinol, this protracted half-life metabolite can account for the reported higher activity of idarubicin as compared to daunorubicin. PMID- 1592362 TI - Effects of recombinant human interferon-alpha, beta and gamma on the antiproliferative activity of cytarabine in K562 human myeloid leukemia clonogenic cells. AB - The effects of recombinant human interferon-alpha, beta and gamma (IFN) on the antiproliferative activity of cytarabine (ara-C) in K562 human myeloid leukemia clonogenic cells were studied in an agar capillary microassay. The addition of IFN-alpha did not affect the antiproliferative activity of ara-C in K562 cultures treated with low concentrations of ara-C: 10-50 nM, whereas in those treated with high concentrations of ara-C: 100-500 nM, IFN-alpha significantly reduced the antiproliferative activity of ara-C. The addition of 3 x 10(4) U/ml IFN-alpha to ara-C-treated K562 cultures increased the IC50 of ara-C on day 5 from 102 to 214 nM, i.e. ara-C+IFN-alpha was about twofold less potent than ara-C alone. Low concentrations of IFN-beta and IFN-gamma did not affect the antiproliferative activity of ara-C on K562 colonies, but high concentrations of these two interferons reduced the antiproliferative activity of ara-C. The addition of 4 x 10(3) U/ml IFN-beta or 10(4) U/ml IFN-gamma increased the IC50 of ara-C on day 5 to 304 nM or to 316 nM, respectively, i.e. ara-C+IFN-beta or IFN-gamma was about threefold less potent than ara-C alone. The significant reduction of the desired antiproliferative activity of ara-C by the three interferons was reproduced in liquid suspension cultures of K562 cells on day 4 in the following order: IFN gamma greater than IFN-beta greater than IFN-alpha. The present negative interactions of the three interferons with ara-C particularly at high concentrations, may caution against the clinical use of the combination of ara-C and interferon in the treatment of myeloid leukemia patients. PMID- 1592363 TI - The biological and clinical significance of the KI-67 growth fraction in multiple myeloma. AB - We tested the significance of the Ki-67 plasma cell growth fraction in 49 bone marrow samples from 42 patients with multiple myeloma (MM). As a new approach to study myeloma cell proliferation, strong positivity of the CD38 antigen as plasma cell related feature was simultaneously evaluated with nuclear Ki-67 expression in a flow cytometric double immunofluorescence assay. Mean Ki-67 values were significantly higher in MM at relapse (22.4 per cent +/- 10.4) as compared with MM at diagnosis (11.9 per cent +/- 8.4, p less than 0.005) and plateau-phase (10.0 per cent +/- 5.5, p less than 0.001), respectively. Serial observations in six patients confirmed this change in cell kinetic behaviour during the course of the disease. Elevated Ki-67 values correlated significantly with stage III (versus stage I, p less than 0.05), beta-2-microglobulin serum levels greater than 6 (p less than 0.001), plasmablastic morphology (p less than 0.001), and diploid myeloma cell DNA-content (p less than 0.005). No correlation was found between Ki-67 and immunoglobulin isotypes as well as immunophenotypic features (expression of CD10, CD33, and CD56) of myeloma cells. Clinically, six of seven patients with Ki-67 greater than 14 per cent at diagnosis had an unfavourable course (primary resistant disease or early relapse), and three of four patients with elevated Ki-67 values at plateau-phase relapsed within 3 months. Our results demonstrate the usefulness of Ki-67 in determining proliferative activity in MM and emphasize its value in the evaluation of the risk profile of MM patients. PMID- 1592364 TI - Specific cutaneous involvement in Hodgkin's disease. AB - In Hodgkin's disease (HD) specific cutaneous involvement is rare. When it occurs, retrograde lymphatic spread, direct extension from the underlying lymph nodes, and hematogenous dissemination are the mechanisms usually implicated. Among 349 patients with HD diagnosed and followed-up at our institution from 1969 to 1990, three (0.85 per cent) presented specific cutaneous involvement. In two cases with mixed cellularity subtype, skin lesions displayed histologic features similar to those found in the lymph node. Treatment with combination chemotherapy resulted in rapid disappearance of the lesions in two patients but was ineffective in the third. Previous reports of cutaneous involvement in HD, its differential diagnosis, prognostic significance, and treatment are briefly reviewed. PMID- 1592365 TI - Failure of IMVP-16 as second-line treatment for relapsed or refractory high grade non-Hodgkin's lymphoma. AB - The British National Lymphoma Investigation (BNLI) has assessed the use of an IMVP-16 regimen (ifosfamide, methotrexate, VP-16) in 46 patients with high grade non-Hodgkin's lymphoma (NHL) who on first-line chemotherapy either failed to attain a complete remission or relapsed. Seventeen patients responded to IMVP-16 but only five (11 per cent) went into a complete remission (CR), 12 (26 per cent) had a partial remission (PR) and 29 (63 per cent) showed no response (NR). CR after IMVP-16 has been maintained in only one case (36 months). The results of this study imply that the use of this IMVP-16 protocol as second-line treatment for patients with recurrent high grade NHL is unsuccessful and alternative salvage regimens should be sought. PMID- 1592366 TI - Etoposide in combination with intermediate dose cytosine arabinoside (ID ARA C) given with the intention of further myeloablative therapy for the treatment of refractory or recurrent hematological malignancy. AB - Thirty-four patients with refractory or recurrent high grade non-Hodgkin's lymphoma (NHL) or acute leukemia were treated with a combination of etoposide, 100 mg/m2 daily, and ara C, 1 g/m2 twice daily, for 5 days (VPARAC). This therapy was given in the anticipation that remissions thus achieved would be 'consolidated' with myeloablative therapy supported by bone marrow transplantation (BMT). The complete remission rate (CR) in patients with NHL was 3/18 (17 per cent) with partial responses (PR) seen in a further four patients, giving an overall response rate of 39 per cent. Four patients (three in CR, one in PR) proceeded to the planned consolidation treatment. Complete remission was achieved in 2/8 (25 per cent) patients with acute myelogenous leukemia (AML) and in 2/8 patients with acute lymphoblastic leukemia (ALL). Three of these patients subsequently had myeloablative consolidation therapy with BMT. There were four treatment-related deaths (NHL, two; AML, one; ALL, one). In poor risk patients with high grade NHL and acute leukemia, VPARAC is an effective remission induction programme in 21 per cent of patients. Seven of the original 34 patients received the intended 'curative' therapy, of whom only four are alive and well 1 year later. PMID- 1592367 TI - A new monoclonal antibody which binds to the cytoplasm of large cell lymphomas. AB - We reported a new monoclonal antibody, designated FUB-1, reacting with normal and neoplastic large lymphoid cells. FUB-1 was produced using a Burkitt's lymphoma cell line (HBL-5) as an immunogen. Its immunoglobulin subtype was IgM. The determinant was not on the surface but in the cytoplasm. Western blotting analysis revealed that the molecular weight of the antigen was 52,000 dalton. In the normal lymphoid tissue, FUB-1 reacted with large lymphoid cells, but not with small or medium-sized lymphoid cells or plasma cells. In addition, the FUB-1 antigen was not found in resting cells in the peripheral blood (PB), but it was induced on mononuclear cells of PB by addition of PWM or PMA. In the B-cell lymphomas tested, FUB-1 reacted with small cleaved cell lymphomas (3/12), large cell lymphomas (7/10), Burkitt's lymphomas (4/4) and immunoblastic lymphomas (2/2), but not with small cell lymphomas (0/3) or intermediate lymphocytic lymphomas (0/8). These findings indicate that the FUB-1 antigen appears to be expressed on normal lymphoid cells during blastoid transformation and on neoplastic large lymphoid cells. FUB-1 also reacted with normal glandular epithelium and various adenocarcinomas. FUB-1 may be useful to investigate the mechanism of in vitro blastoid transformation or activation of lymphoid cells. PMID- 1592368 TI - Data watch. CEOs identify sources of tension with medical staff. PMID- 1592369 TI - The CEO experience. TQM/CQI. AB - The total quality movement is transforming hospital leadership. CEOs are finding that signing on to a TQM or CQI program requires intensive commitment, as well as adjustments to management style and scheduling. And it raises a host of questions about how to initiate and manage such a program--and even what to call it (TQM versus CQI). But CEOs seem ready to accept the challenge. An exclusive Hospitals survey finds that over 60 percent of the CEOs involved in TQM/CQI programs believe their involvement is "the most important thing I've ever done." Still, the proliferation of TQM/CQI in hospitals has created a backlash in the field; Donald Berwick, M.D., the "father" of TQM in health care, explains why. PMID- 1592370 TI - Health care surveys: pollsters present debatable results. AB - The public is being surveyed more often than ever before on health care reform. But experts say pollsters aren't clarifying people's thoughts as well as they should. Then again, the public's thoughts on health care aren't very clear. PMID- 1592371 TI - Contracting: how to gain the information edge over HMOs. AB - Hospitals face significant information-oriented challenges in the managed care area, say experts. They need to get both detailed internal reports on their own costs, utilization and resource consumption. PMID- 1592372 TI - Well-managed information vital to effective managed care contracting. PMID- 1592373 TI - States scramble for solutions under new Medicaid law. PMID- 1592374 TI - Hospitals move toward image management, but pace is slow. PMID- 1592375 TI - CEOs: no regrets about their career choice. PMID- 1592376 TI - New guide offers planning tips for preventive care. PMID- 1592377 TI - Health insurance futures market faces hard sell. PMID- 1592378 TI - Group creates new prototypes of geriatric care. PMID- 1592379 TI - Taking environmental action: what you can do. PMID- 1592380 TI - Improved methods of estimating mitotic activity in solid tumors. PMID- 1592381 TI - Reproducibility of mitosis counting in 2,469 breast cancer specimens: results from the Multicenter Morphometric Mammary Carcinoma Project. AB - The Multicenter Morphometric Mammary Carcinoma Project is a prospective study on the reproducibility and prognostic value of routine quantitative assessments, especially the mitotic activity index (MAI), the multivariate prognostic index (MPI; a combination of MAI, tumor size, and lymph node status), the mean nuclear area, and DNA ploidy assessments in patients with invasive breast cancer. Fourteen pathology laboratories providing routine services to 35 hospitals throughout The Netherlands are participating in this project. In this article, the reproducibility of MAI and MPI assessments is described. Assessment of the MAI was, according to a strict protocol, first performed in the participating laboratories; thereafter, slides were transferred to the coordination center in Amsterdam for quality control. Analysis of the reproducibility of the assessments in 2,469 patients showed correlation coefficients between 0.81 and 0.96 (mean, 0.91) for the MAI and between 0.91 and 0.97 (mean, 0.96) for the MPI. The reproducibility was fairly constant in time, although it showed a slight drop in the middle of the 2-year intake period. A prognostically relevant discrepancy in MPI (caused by differences in MAI) between the original and quality control assessments was found in only 7.2% of the cases. When analyzing the reasons for these discrepancies, a plausible explanation could be found in all cases: bad tissue processing and ignorance of or negligence in following the protocol guidelines for selection of the counting area or in the process of counting were the most important flaws. Since these errors are largely controllable, an even lower discrepancy rate is theoretically achievable. In conclusion, in a routine setting it can be learned, within a reasonable time, to perform mitosis counting in a highly reproducible way if a strict protocol is carefully followed. This opens the way for a wider application of the MAI and MPI in breast cancer patients. Motivation is, however, an important factor to obtain reproducible results, and ongoing quality control is essential to guarantee the reproducibility of the assessments. PMID- 1592382 TI - Expression of mitoses per thousand cells and cell density in breast carcinomas: a proposal. AB - A method of standardizing mitotic counts is described. This provisional approach, which expresses mitoses as a percentage of breast cancer cells present, holds the promise of facilitating interlaboratory agreement as well as providing a measure of tumor cellularity, probably an independent prognostic indicator in its own right. We suggest that this approach or one similar to it will maximize the evaluation and quantitation of proliferative activity from routinely available histologic material. Furthermore, the method is accomplished with little added effort beyond the customary histologic evaluation. PMID- 1592383 TI - Correlation of Pneumocystis carinii cyst density with mortality in patients with acquired immunodeficiency syndrome and pneumocystis pneumonia. AB - Fifteen percent to 20% of patients with the acquired immunodeficiency syndrome and pneumocystis pneumonia do poorly despite early intervention. It is not known what distinguishes those who die, despite early intervention and aggressive therapy, from those who readily respond to therapy. We used image analysis to determine the relative abundance of cysts within aggregates of Pneumocystis carinii found in induced sputa (21 patients) and bronchoalveolar lavage fluid (14 patients) from 35 patients with pneumocystis pneumonia. We calculated a cyst density (number of cysts per area of aggregate) for each aggregate and a mean cyst density for all of the aggregates on the smear. Six patients died within 2 weeks of diagnosis; four of these six patients who had autopsies all had residual P carinii. The mean cyst density for those who died was 9.7 +/- 3.9 (range, 5 to 15 x 10(-3)). The 29 patients who survived beyond 2 weeks had a mean cyst density of 18.4 +/- 8.7 (range, 5 to 35 x 10(-3); P = .01). Mean cyst density was not influenced by the number of aggregates present in the smear, the variation in cyst density among aggregates in a smear, or the episode of pneumocystis pneumonia. Cyst density determinations alone should not be used to predict outcome for individuals with P carinii pneumonia until further study is completed. Nevertheless, the current study suggests that a low cyst density specimen, which may indirectly indicate a greater proportion of trophozoites compared with a high cyst density specimen, may be associated with an unfavorable outcome in acquired immunodeficiency syndrome-associated pneumocystis pneumonia. PMID- 1592384 TI - Neutrophils as mediators of human skeletal muscle ischemia-reperfusion syndrome. AB - Nine patients with aortic aneurysm undergoing arterial reconstruction with temporary aortic occlusion were studied. Since a typical condition of ischemia reperfusion of the muscles of the lower limbs was created during this surgery, muscle biopsies from the right femoral quadriceps as well as blood samples from the homolateral saphenous vein were taken: (1) before clamping of the aorta, (2) just before declamping, and (3) 30 minutes after reperfusion. Light microscopy revealed a consistent granulocyte infiltration in the ischemic and reperfused skeletal muscle. Ultrastructural damage to the muscle fibers was seen during ischemia and became more severe upon reperfusion. The recruitment of granulocytes into the muscle tissue paralleled the activation of the blood complement system and an increase in circulating neutrophils. Although a spontaneous superoxide anion (O2-) generation from such granulocytes cannot be proved, upon stimulation with formyl-methionyl-leucyl-phenylalanine neutrophils showed a reduced ability in O2 free radical production at the end of ischemia and enhanced O2- generation at reperfusion as compared with the controls. All these findings indicate an active role of granulocytes in the genesis of reperfusion-induced tissue injuries. PMID- 1592385 TI - The nonrandom regional distribution of uterine leiomyomas: a clue to histogenesis? AB - Although uterine leiomyomas are a major public health problem, very little is known about their etiology or histogenesis. To seek clues as to why the myometrium so frequently gives rise to these tumors, we attempted to determine if the regional distribution of leiomyomas was uniform. It appears that the proportion of leiomyomas in the premenopausal (0.8%) and postmenopausal (3.7%) cervix may be substantially less than the proportion of smooth muscle in the premenopausal (7.3%) and postmenopausal (17%) cervix. These data suggest that the smooth muscle cells of the corpus uteri may be at higher risk for neoplastic transformation than those of the cervix. Within the corpus there appeared to be a relative excess of fundic leiomyomas (premenopausal, 89%; postmenopausal, 86%) as compared with fundic smooth muscle (premenopausal, 79%; postmenopausal, 61%). No such excess was apparent in the isthmus or cornu. Immunohistochemical studies of estrogen and progesterone receptors in premenopausal and postmenopausal myometrium were uniformly positive, with no regional differences to suggest a hormonal basis for regional susceptibility to leiomyomas. It may be fruitful to search for precursor lesions and other factors predisposing to neoplastic development in fundic myometrium. PMID- 1592386 TI - Juxta-articular myxoma: a clinical and pathologic study of 65 cases. AB - We describe 65 cases of juxta-articular myxoma (JAM) that occurred in the vicinity of large joints, possessed histologic features of a myxoma, and were frequently associated with cystic changes that resembled a ganglion cyst. The vast majority of cases (57, 88%) occurred in the region of the knee; a minority involved the shoulder (three cases), elbow (three), ankle (one), and hip (one) regions. Patients' ages ranged from 16 to 83 years (median, 43 years; mean, 44 years) and nearly three fourths of the patients (72%) were male. Thirty-seven lesions presented as a swelling or mass, 21 were associated with pain or tenderness, and sizes ranged from 0.6 to 12 cm (median, 3.5 cm; mean, 3.8 cm). Duration of symptoms was highly variable, spanning from 1 week to 18 years. Fourteen JAMs were intimately associated with the meniscus and five of these had a concomitant tear; in five other cases JAM was an incidental finding at the time of total knee or hip arthroplasty for severe osteoarthritis. Of 29 cases with follow-up, 10 (34%) recurred: five recurred once, two recurred twice, two recurred three times, and one recurred four times. While the majority of JAMs were correctly diagnosed as benign, a sarcoma was seriously considered or diagnosed in 15 (23%) cases. PMID- 1592387 TI - Immunophenotypic characterization of the cell infiltrate in five cases of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease). AB - Little is known about the nature of the large intrasinusoidal cells exhibiting cytophagocytosis, which are the histologic hallmark of sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease). Using a broad panel of monoclonal and polyclonal antibodies, we analyzed the immunophenotype of the cell infiltrates in seven lymph node biopsy specimens from five cases of SHML. The SHML cells constantly expressed the S-100 protein, concanavalin agglutinin and peanut agglutinin lectins, and monocyte-macrophage-associated antigens CD 11c, CD 14, CD 33, CD 68, and LN 5. Labeling with other antimacrophage antibodies was extremely variable, with some (MAC 387, lysozyme) restricted to clusters of SHML cells and others (CD11b, CD 36, alpha-1-antichymotrypsin) staining only scattered cells. The CD 1a antigen was found on some cells in only one case, whereas HLA-DR and the HLA-DR-associated invariant chains were absent. The heterogeneity of SHML cell marker expression might be related to the local content of factors (eg, cytokines) capable of modulating the phenotype of monocytes and derived cells. All cases presented with huge amounts of medium-sized mononuclear cells accumulated in the sinuses and intersinusoidal tissue. These cells expressed the S-100-/CD 11b+/CD 11c+/CD 14+/CD 16+/CD 33+/CD 36+/lysozyme+/MAC 387+/HLA-DR+ phenotype. These recently immigrated monocytes might represent the immediate precursors of SHML cells. PMID- 1592388 TI - Pleomorphic lobular carcinoma of the breast: an aggressive tumor showing apocrine differentiation. AB - Pleomorphic lobular carcinoma of the breast is a recently recognized subtype of invasive lobular carcinoma (ILC). Cytologic features are pleomorphic to a degree that contrasts with the cytologic uniformity of classic ILC. It is this feature that simultaneously gives its name to the tumor and highlights the difficulty of identifying it correctly and distinguishing it from ductal carcinoma. In our series of 10 cases, six tumors also contained lobular carcinoma in situ. Nodal metastases were typically sinusoidal. All tumors showed the dissociated, linear, and single file pattern of classic ILC, together with a targetoid distribution. Intracytoplasmic lumina were present in 50% of the tumors. An eosinophilic, slightly granular cytoplasm suggests the possibility of apocrine differentiation, a suggestion derived also from the frequent presence of foamy cells, a cell type previously identified in histiocytoid lobular carcinoma and shown to have apocrine features. The GCDFP-15 apocrine marker was positive in all 10 tumors, while all control ILCs were negative, confirming the presence of apocrine differentiation in pleomorphic lobular carcinoma. Six of 10 patients died within 42 months of diagnosis. Three other patients developed recurrence or distant metastases at short intervals. Pleomorphic lobular carcinoma is a very aggressive tumor. This behavior is perhaps predictable on the basis of tumor size at presentation and the frequency of nodal metastases. Since grading of lobular carcinoma is difficult, recognition of the pleomorphic subtype is useful in identifying a lethal variant. PMID- 1592389 TI - Progressive multifocal leukoencephalopathy in patients with human immunodeficiency virus. AB - Lesions of progressive multifocal leukoencephalopathy (PML) in patients infected with the human immunodeficiency virus (HIV) often have mononuclear cell infiltrates so intense that they obscure the nature of the lesion. This response may be especially prominent in stereotactic biopsies of contrast-enhancing areas. Of 10 consecutive PML lesions biopsied stereotactically, three were markedly, two were moderately, and five were mildly inflamed. There were few to no enlarged oligodendrocytic nuclei with inclusions in the markedly and moderately inflamed lesions. We investigated all biopsies with immunoperoxidase, DNA in situ hybridization, polymerase chain reaction, and Southern immunoblot methodologies for toxoplasmosis and the following viruses: JC, cytomegalovirus, herpes simplex viruses I and II, and human T-cell lymphotropic viruses I, II, and III. We confirmed the presence of JC virus in each lesion; polymerase chain reaction revealed HIV genome only in one. Inflammatory PML lesions in HIV+ patients do not reflect co-infection with toxoplasmosis or viruses commonly seen in these patients. The mononuclear cells are primarily T lymphocytes. Patients with severely inflamed PML lesions, whether HIV+ or not, often show stabilization of symptoms with or without antiviral treatment and have longer lengths of survival than patients with less inflamed lesions. PMID- 1592390 TI - Life history of cutaneous vascular lesions in Sneddon's syndrome. AB - Sneddon's syndrome is a potentially fatal arterio-occlusive disorder characterized by generalized livedo racemosa and cerebrovascular lesions. Skin biopsies often fail to yield diagnostic arterial lesions. In the present series, affected vessels were found in skin biopsies from 12 of 15 patients with Sneddon's syndrome. Selection of the correct biopsy site (seemingly uninvolved skin at the center of a livedo racemosa area), adequate biopsy size (1 to 2 cm), and serial sections are essential for the detection of relevant vascular pathology. Only small to medium-sized arteries of the dermis-subcutis boundary were found to be involved. Lesions follow a distinct course. The initial stage displays partial detachment of endothelial cells, adhesion of mononuclear cells interspersed with fibrin ("endothelitis"), a marked edema of the surrounding connective tissue with numerous dilated capillaries, and a predominantly lymphohistiocytic infiltrate with polymorphonuclear leukocytes. In the early phase a sponge-like plug is formed from mononuclear cells, fibrin, and red blood cells, leading to partial to complete obstruction. A perivascular inflammatory infiltrate, devoid of polymorphonuclear leukocytes, is located around affected arteries; in the adventitia of the occluded vessel, a very regular corona of dilated capillaries appears that is continuous with more peripheral dilated and branching vessels. Organization of the occluding plug ensues in the intermediate stage by "subendothelial cell proliferation," most likely due to immigrating smooth muscle cells. In the final stage, the occluding artery undergoes fibrosis, shrinkage, and atrophy. PMID- 1592391 TI - Immunohistochemical monitoring of plasmacytoid cells in lymph node sections of Kikuchi-Fujimoto disease by a new pan-macrophage antibody Ki-M1P. AB - The new monoclonal antibody Ki-M1P, which detects a formalin-resistant epitope on conventional paraffin sections, was applied in 20 cases of different stages of Kikuchi-Fujimoto disease. This new pan-macrophage immunoreagent detects plasmacytoid T cells, referred to as plasmacytoid cells, and renders a reliable delineation of these cells against other similar cell types, such as blasts of high-grade B- and T-cell lymphoma. Histiocytes as well as macrophages were strongly positive, and plasmacytoid cells showed a somewhat weaker and primarily granular, intracytoplasmic immunoreactivity. Plasmacytoid cells, being a diagnostic feature of the Kikuchi-Fujimoto disease, facilitate a clear distinction of this disease entity from large cell or high-grade lymphomas. These results may represent an additional argument favoring the histiocytic origin of plasmacytoid cells. Additionally, they may point to an immunohistochemical tool that facilitates the differential diagnosis between Kikuchi-Fujimoto disease, especially in early stages of the disease, and malignant lymphoma. PMID- 1592392 TI - Immunohistochemical study of epidermal growth factor and transforming growth factor-beta in the penetrating type of early gastric cancer. AB - We report that the penetrating type of early gastric cancer (PEN) is a specific type of early gastric cancer and that the poorly differentiated PEN type could be considered an initial lesion of linitis plastica-type cancer. We performed an immunohistochemical study to clarify the role of growth factors (epidermal growth factor [EGF] and transforming growth factor-beta [TGF-beta]) in the PEN type of early gastric cancer. The results indicated that the PEN type of early gastric cancer has a high growth capacity. Moreover, it was suggested that EGF was involved in its specific infiltrative growth and that both EGF and TGF-beta were involved in its specific scirrhous growth. From these findings, it was assumed that the immunohistochemical staining of EGF and TGF-beta in endoscopic biopsy specimens was useful for the diagnosis of the PEN type of gastric cancer and also for the diagnosis of the initial lesion of linitis plastica-type gastric cancer. PMID- 1592393 TI - Immunoarchitecture of normal human bone marrow: a study of frozen and fixed tissue sections. AB - To provide baseline information on the immunoarchitecture of normal bone marrow, we studied cryostat-cut, frozen, and paraffin-embedded, fixed tissue sections prepared from 21 core biopsies of normal bone marrow obtained during bone marrow harvests for transplantation. A large panel of antibodies was applied that included, for frozen tissue, Leu-6 (CD1), T11 (CD2), Leu-3a (CD4), Leu-1 (CD5), Leu-2a (CD8), J5 (CD10), My7 (CD13), Leu-11 (CD16), B4 (CD19), B1 (CD20), B2 (CD21), Tac (CD25), My9 (CD33), T200 (CD45), NKH-1 (CD56), kappa and lambda chains, beta F1, Ki-67, HLA-DR, TQ1, and keratin, and for fixed tissue, leukocyte common antigen (CD45), L26 (CD20), LN1 (CDw75), LN2 (CD74), LN3, LN4, LN5, MB1 (CD45R), MB2, MT1 (CD43), MT2 (CD45R), UCHL1 (CD45R0), BM1, Ki-1 (CD30), Leu-M1 (CD15), lysozyme, KP1 (CD68), actin, S100, neuron-specific enolase, vimentin, and keratin. On fresh-frozen sections CD19 and CD2 were the most reliable and sensitive markers for B and T cells, staining 5% and 9% of marrow cells, respectively. Immunoglobulins generally showed heavy background staining, which frequently precluded an accurate assessment. The CD4 to CD8 ratio in the bone marrow was reversed from that of peripheral blood. On fixed tissues, leukocyte common antigen was found in 14% of the marrow cells, corresponding roughly to the lymphocyte population. L26, a pan-B-cell marker, stained 3% of the marrow cells. Among the other B-cell markers, LN1 and MB2 stained a large number of cells (40% to 70%), indicating reactivity with cells of the myeloid or erythroid series in addition to lymphocytes. Among the T-cell markers, UCHL1 and MT1 stained 66% and 50% of the cells, respectively, which could be explained by their cross reactivity with myeloid cells. Nonspecific myelomonocytic markers (Leu-M1, KP1, and lysozyme) also showed reactivity in a high percentage of cells. No particular architectural distribution patterns of B or T lymphocytes were noted in either frozen or fixed bone marrow specimens. The results of this study provide normal baseline data for the immunohistologic application of hematopoietic and lymphoid markers on frozen or fixed bone marrow biopsy specimens. PMID- 1592394 TI - Stromal osteoclast-like giant cells in an adenosquamous carcinoma of the gallbladder. AB - We report a case an adenosquamous carcinoma of the gallbladder that extended to the proximal transverse colon. Metastatic tumor was present in regional lymph nodes and the liver. Microscopically, the tumor was composed of malignant epithelial cells that were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-positive. The adjacent desmoplastic stroma of the primary tumor, as well as the metastasis, contained giant cells that morphologically resembled osteoclasts. Immunohistochemical studies showed that the giant cells were cytokeratin-, epithelial membrane antigen-, and carcinoembryonic antigen-negative but weakly alpha 1-antichymotrypsin-positive. While tumors containing osteoclast-like giant cells have been described in the breast, lung, liver, and thyroid, this is the first report of a tumor with this morphology originating in the gallbladder. The presence of the giant cells adjacent to both the primary and metastatic tumor and not at any other location suggests that the tumor cells are producing a substance that induces the formation of the nontumoral giant cells. PMID- 1592395 TI - Oligodendroglial gliomatosis cerebri. AB - A 34-year-old man presented with progressive neurologic deterioration though clinically to be multiple sclerosis. At autopsy, the cerebral white matter, deep gray matter, and brain stem were diffusely infiltrated with cells characteristic of oligodendrocytes. Gliomatosis cerebri consisting predominantly of oligodendroglia is rare. PMID- 1592396 TI - Cervical paravertebral leiomyosarcoma mimicking a nerve sheath tumor. AB - A rare case of leiomyosarcoma attached to the C6 nerve root with extension through the intervertebral foramen into the spinal canal is described. Clinically and at the time of frozen section, this was considered to be a nerve sheath tumor. A definitive histologic diagnosis was made on the basis of the ultrastructural features of the tumor. Complete remission was achieved following extensive surgical removal and postoperative radiotherapy. The possible origin of this neoplasm is discussed. PMID- 1592397 TI - Neural-network-based adaptive matched filtering for QRS detection. AB - We have developed an adaptive matched filtering algorithm based upon an artificial neural network (ANN) for QRS detection. We use an ANN adaptive whitening filter to model the lower frequencies of the ECG which are inherently nonlinear and nonstationary. The residual signal which contains mostly higher frequency QRS complex energy is then passed through a linear matched filter to detect the location of the QRS complex. We developed an algorithm to adaptively update the matched filter template from the detected QRS complex in the ECG signal itself so that the template can be customized to an individual subject. This ANN whitening filter is very effective at removing the time-varying, nonlinear noise characteristic of ECG signals. Using this novel approach, the detection rate for a very noisy patient record in the MIT/BIH arrhythmia database is 99.5%, which compares favorably to the 97.5% obtained using a linear adaptive whitening filter and the 96.5% achieved with a bandpass filtering method. PMID- 1592398 TI - Data compression of ECG's by high-degree polynomial approximation. AB - A method for the compression of ECG data is presented. The method is based on high-degree polynomial expansions. Data rates of about 350 bits per second are achievable at an acceptable signal quality. The high compression is obtained by a carefully selected subdivision of the ECG signal into intervals that make optimal use of the special properties of the polynomial base functions. Each interval corresponds to one ECG period. The method is compared to the discrete cosine transform and is found to yield a significantly higher data compression for a given signal quality (quantified by mean squared error and peak error). PMID- 1592399 TI - Weighted averaging of evoked potentials. AB - Weighted averages of brain evoked potentials (EP's) are obtained by weighting each single EP sweep prior to averaging. These weights are shown to maximize the signal-to-noise ratio (SNR) of the resulting average if they satisfy a generalized eigenvalue problem involving the correlation matrices of the underlying signal and noise components. The signal and noise correlation matrices are difficult to estimate and the solution of the generalized eigenvalue problem is often computationally impractical for real-time processing. Correspondingly, a number of simplifying assumptions about the signal and noise correlation matrices are made which allow an efficient method of approximating the maximum SNR weights. Experimental results are given using actual auditory EP data which demonstrate that the resulting weighted average has estimated SNR's that are up to 21% greater than the conventional ensemble average SNR. PMID- 1592400 TI - Probabilistic inference-based classification applied to myoelectric signal decomposition. AB - A new probabilistic inference based technique (IBC) for the classification of motor unit action potentials (MUAP's) is presented. This new technique discovers statistically significant relationships in the data and uses these relationships to generate classification rules. The technique was applied to the classification of MUAP's extracted from simulated myoelectric signals. Its performance was compared to that of classical template matching algorithms (TBC) applied to the same data. Using 32 time samples as features to represent the MUAP's it was found that the IBC based technique performed significantly better (p less than 0.005) than the TBC algorithms (83.0 +/- 2.6% versus 78.1 +/- 2.8% peak correct classification performance). As the size of the training set was reduced or as increasing numbers of random classification errors were introduced into the training data, the performance of the IBC and TBC techniques declined similarly. IBC performance remained superior until very small training sets (less than 30 MUAP's per motor unit) or training sets with large numbers of errors (greater than 50%) were used. Because the probabilistic inference technique can utilize nominal data it has the potential to use declarative problem domain knowledge which conceivably could improve its performance. PMID- 1592402 TI - Nonlinear joint angle control for artificially stimulated muscle. AB - Designs of both open- and closed-loop controllers of electrically stimulated muscle that explicitly depend on a nonlinear mathematical model of muscle input output properties are presented and evaluated. The muscle model consists of three factors: a muscle activation dynamics factor, an angle-torque relationship factor, and an angular velocity torque relationship factor. These factors are multiplied to relate output torque to input stimulation and joint angle. An experimental method for the determination of the parameters of this model was designed, implemented, and evaluated. An open-loop nonlinear compensator, based upon this model, was tested in an animal model. Its performance in the control of joint angle in the presence of a known load was compared with a PID controller, and with a combination of the PID controller and the nonlinear compensator. The performance of the nonlinear compensator appeared to be strongly dependent on modeling errors. Its performance was roughly equivalent to that of the PID controller alone: somewhat better when the model was accurate, and somewhat worse when it was inaccurate. Combining the nonlinear open loop compensator with the PID feedback controller improved performance when the model was accurate. PMID- 1592401 TI - Goodness-of-fit and local identifiability of a receptor-binding radiopharmacokinetic system. AB - A four-state nonlinear model describing a radiopharmacokinetic system for a hepatic receptor-binding radiopharmaceutical, [99mTc]-galactosyl-neoglycoalbumin (TcNGA), was tested for goodness-of-fit and local identifiability using scanning data from nine healthy subjects and seven patients with severe liver disease. Based on standard deviations of liver and heart imaging data at equilibria as a measure of observational error, the reduced chi-square ranged from 0.5 to 2.6. Values above 1.2 occurred when the subject moved during the 30 min study. Relative standard errors for each parameter were: TcNGA-receptor forward binding rate constant kb, 13-54%; extra-hepatic plasma volume Ve, 0.8-15.0%; hepatic plasma volume Vh, 0.2-6.5%; hepatic plasma flow F, 54----greater than 1000%; and receptor concentration [R]o, 0.3-13%. The highest standard errors occurred when the amount of TcNGA injected exceeded the total amount of receptor. Therefore, when TcNGA functional imaging was performed without excess patient motion and receptor saturation, the kinetic model provided data fits of low systematic error and yielded high precision estimates of receptor concentration and forward binding rate constant. In summary, optimal performance of the kinetic model occurred when the amount of injected TcNGA resulted in the nonlinear operation of the pharmacokinetic system. PMID- 1592403 TI - Improved safety and efficacy in adaptive control of arterial blood pressure through the use of a supervisor. AB - This paper presents a dual approach to adaptive control of arterial blood pressure using sodium nitroprusside. In the clinical environment, a controller must be aggressive to achieve specific step response characteristics (less than 10 min settling time, less than 10 mm Hg overshoot), yet conservative enough to prevent overreactions to large disturbances, which are common in both the operating room and the intensive care unit. These mutually exclusive requirements make it difficult to design a closed-loop controller for this environment. To prevent possible overreactions, while maintaining proper step response, an aggressive adaptive controller has been designed to achieve the desired step response, and a SUPERVISOR has been designed around the adaptive controller to limit potential overreactions in the presence of disturbances. Simulations and dog experiments demonstrate the potential for increased safety and efficacy using this dual approach to the control of a complex physiological system. PMID- 1592404 TI - Supervisory adaptive control of arterial pressure during cardiac surgery. AB - A supervisory adaptive controller has been designed for the closed-loop control of mean arterial pressure during cardiac surgery, using sodium nitroprusside. This controller consists of a pole-placement and proportional-plus-integral feedback regulator, multiple-model adaptation, and a supervisor. The pole placement and proportional-plus-integral regulator was designed to meet aggressive step response characteristics. Multiple-model adaptation was chosen to ensure rapid and stable adjustments for changes in key patients parameters. The supervisor was designed to provide safety and efficacy of control during disturbances that are common during cardiac surgery. We studied the ability of this supervisory adaptive controller to regulate arterial pressure during cardiac surgery on nineteen patients. The controller, through the action of the supervisor, detected and responded appropriately to the great majority of disturbances. This study demonstrated that supervisory adaptive control has the potential to provide clinically acceptable regulation of arterial pressure. PMID- 1592405 TI - An optimal controller for an electric ventricular-assist device: theory, implementation, and testing. AB - This paper addresses the development and testing of an optimal position feedback controller for the Penn State electric ventricular-assist device (EVAD). The control law is designed to minimize the expected value of the EVAD's power consumption for a targeted patient population. The closed-loop control law is implemented on an Intel 8096 microprocessor and in vitro test runs show that this controller improves the EVAD's efficiency by 15-21%, when compared with the performance of the currently used feedforward control scheme. PMID- 1592406 TI - Temporal relationship between left ventricular and arterial system elastances. AB - Arterial compliance is an important component of ventricular afterload. Although its pressure dependence has been recognized, its temporal relationship to ventricular elastance (Elv(t)) has not been established. We investigated this in five open chest anesthetized dogs where simultaneous aortic pressure and flow and left ventricular pressure were measured. Elv(t) was derived using an elastance resistance model of the left ventricle assuming an ejection fraction of 0.50 and a dead volume (Vd) of 3.0 mL. The nonlinear pressure-dependent compliance (C(P)) of the arterial system was incorporated in a three-element Windkessel model and determined by accurate prediction of aortic pressure from aortic flow. The resulting arterial elastance (Eas(t)) was computed as Eas(t) = 1/C(P). Results show that Eas(t) reaches a minimum value at or near the start of ventricular ejection and attains its peak value at or near the same time maximum LV elastance (Emax) is reached, at end-systole. Finally, numerical simulation of the model demonstrates its ability to adequately reproduce measured pressure and flow. Thus, the arterial system, in terms of elastance, is dynamically and temporally coupled to the left-ventricle during ejection. PMID- 1592407 TI - Electrical impedance of layered atherosclerotic plaques on human aortas. AB - Electrical impedance measurements were performed on 13 atherosclerotic human aortic segments at 67 measuring spots in order to determine whether or not on the basis of these data a distinction can be made between atherosclerotic lesions and normal tissue. Stenosis localization and guidance of interventional techniques could be among the applications of an impedance measuring technique implemented on a catheter system. The experimental results, obtained with a two-electrode measuring technique, show that the apparent resistivity of an atherosclerotic spot does not necessarily deviate much from the resistivity of normal tissue. This is clarified by histology which shows that the majority of lesions has a surface layer of connective, fibrous tissue having almost similar conducting properties as the normal arterial wall. For gaining a deeper understanding of the way in which the measured data come about, a physical model of an atherosclerotic lesion is presented and confronted with the data. Both experimental data and theoretical considerations lead to the conclusion that only when the superficial fibrous layer is absent or very thin in relation to the size of the measuring electrode, the measured resistivity at a lesion is much higher than at normal spots. This occurs as a consequence of the high ohmic properties of the calcified or lipid deposits in the atherosclerotic lesion. PMID- 1592408 TI - Instantaneous characterization of time-varying nonlinear systems. AB - A nonlinear system may be characterized by an orthogonal functional power series (FPS) computed from cross correlations between input and output variables. "Is the response changing over the course of the experiment?" is a fundamental question encountered in the analysis of both FPS and evoked potentials (EP's). Regression on closed-form functions of time produces a time-varying FPS or EP. Evaluation of these functions at a specified time point produces a system characterization for that instant. PMID- 1592409 TI - A model of safe levels for electrical stimulation. AB - A model is presented that represents a large body of data on safety and damage levels of electrical stimulation. The predictions of the model are consistent with known principles of current flow and known mechanisms of damage around stimulating electrodes. It is proposed that limits on levels of electrical stimulation take into account the location of the electrode relative to the stimulated tissue and these limits can be computed algorithmically from the model. PMID- 1592410 TI - Microcomputer-based portable long-term spasticity recording system. AB - A device for long-term monitoring of muscle activity (EMG) with surface electrodes and method of its application are described in this paper. This device is called a microcomputer two-channel EMG monitor. The device can be used for up to 24 h monitoring of EMG activity, followed by data transfer to a host computer for signal analysis. This device records amplified, rectified, and integrated EMG activity. Shorter recording time allows shorter sampling periods suitable for different other EMG analysis. Recording of spontaneous EMG in complete spinal cord injured subjects was the original reason for the design of the long-term monitor. These recordings were used for estimation of spasticity in complete spinal cord patients. PMID- 1592411 TI - Carbon source for starch biosynthesis in amyloplasts of plant storage tissues. PMID- 1592412 TI - Properties of single-stranded DNA-binding proteins (SSB-proteins) from chromatin and nonchromatin fractions of Ehrlich ascites tumour: phosphorylation enhances the affinity of SSB-proteins for single-stranded DNA. AB - To assess the possible functional role of single-strand DNA-binding (SSB) proteins in eucaryotic cell, a comparative study was made of SSB-proteins isolated from chromatin and the nonchromatin fractions of Ehrlich ascites tumour (EAT) cells. No appreciable differences between the two groups could be found either in SDS-gel electrophoretic patterns or in the ssDNA-binding capacity and stimulation of DNA replication in permeable EAT cells. However, the chromatin SSB proteins incorporated 1.4-times more labelled phosphate in vivo; phosphate assays in the isolated chromatin and nonchromatin SSB-proteins yielded ca. 3 and 2 moles Pi/mole protein, respectively. Both preparations could be further phosphorylated in vitro with Ca-phospholipid-dependent protein kinase and the catalytic subunit of cAMP-dependent protein kinase, but the non-chromatin proteins were phosphorylated to a greater degree. In parallel with phosphorylation, the SSB proteins displayed stronger binding to ssDNA cellulose. Phosphorylation may thus be a means of regulating the functions of SSB-proteins, in particular their interaction with chromatin. PMID- 1592413 TI - Properties of a ribosome-inactivating protein, gelonin, purified using three different methods. AB - Ribosome-inactivating protein, gelonin, isolated from an Indian plant Gelonium multiflorum of Euphorbiaceae family has been used to design and synthesize immunotoxins and hormonotoxins for selective targeting purposes. Since gelonin isolated by aqueous extraction, cation-exchange chromatography and gel-filtration chromatography (Method I), contains non-proteinous material absorbing at 280 nm, the ammonium sulphate precipitation method (Method II) and Cibacron blue affinity chromatography method. (Method III) have been used to purify gelonin from the dry seeds. Three batches of gelonin purified by each method were prepared and subjected to extensive physico-chemical and immunochemical characterization. The molecular weight was determined by gel-filtration chromatography on a pre calibrated Sephadex G-100, TSK-G4000 TW on HPLC or Superose-12 on fast protein liquid chromatography. In all cases, the molecular weight was approximately 30,000Da. The SDS-PAGE also revealed a homogeneous protein of 30kDa molecular weight. In Method II, the non-proteinous material which binds to CMC-gel in association of gelonin was substantially removed during ammonium sulphate fractionation. A careful analysis clearly revealed that Method II, although yielded low protein, gave gelonin devoid of the non-proteinous material. The SPDP modification of epsilon-NH2 groups of gelonin obtained from Methods I, II, and III was also carried out and its effect on immunoreactivity was studied. PMID- 1592414 TI - Rat liver chromatin digested in situ with endogeneous Mg(2+)-dependent deoxyribonuclease exhibits two distinct DNA repeats. AB - Incubation of rat liver nuclei in the presence of 1.0-5.0 mM Mg2+ at 37 degrees C releases oligonucleosomes containing at least two distinct chromatin-DNA repeat elements. The 'short' repeat is derived from the dimer to pentamer series, while the 'long' repeat is found in the monomer and hexamer to decanucleosomes. Both repeat lengths decrease during enzymatic hydrolysis but in 5.0 mM Mg2+, which is optimal concentration, the 'long' repeat is degraded faster. PMID- 1592415 TI - Methylation of DNA of the brain and liver of young and old rats. AB - In vitro methylation of purified DNA and chromatin-DNA in nuclei of the liver and brain of young (18 week) and old (120 week) female rats has been studied using 3H SAM as the -CH3 group donor. Incorporation of -CH3 group is higher in old liver and brain, but it is far higher in the latter. 5 mC is 11% lower in the old brain, but there is no difference in the liver. Methylation by Hpa II methylase does not show any difference in the incorporation of -CH3 group into DNA of the liver of the two ages. However, its incorporation is lower in the old brain. Methylation by Msp I methylase causes slightly higher incorporation of -CH3 groups in the old brain. This shows a higher percentage of unmethylated external cytosines in the 5'-CCGG-3' sequences. On the contrary, methylation by Eco RI methylase is considerably higher in the old brain. These studies show alterations in the methylation status of the DNA during ageing which may cause changes in the expression of genes. PMID- 1592416 TI - Conformational studies on cimetidine and ranitidine by PCILO calculations and NMR spectroscopy. AB - The conformational characteristics of two H2-receptor antagonists, cimetidine and ranitidine, have been investigated by quantum mechanical PCILO method and the results indicate a folded conformation for cimetidine stabilized by intramolecular hydrogen bonding and an extended backbone conformation for ranitidine. NMR investigations carried out on these two drugs in solution, however, indicate a predominance of an extended conformation for both the molecules. The significance of this result has been discussed in terms of the activity of these two drugs. Besides these studies, NMR experiments have also been carried out on the drugs incorporated into the lipid bilayers to investigate the drug-lipid interaction. The results from this study suggest that the hydrophobic portion of the drugs is buried in the hydrophobic hydrocarbon chains of the lipid bilayer, while the terminal hydrophilic end of the drug lies at the lipid-water interface. PMID- 1592417 TI - Nucleophilic scission of thioester linkages and conformational changes in human plasma low density lipoproteins. AB - A comparison between conformations of native and methylamine modified human plasma low density lipoproteins (hydrated density 1.032-1.043 g/ml) has been presented. Near UV circular dichroism and difference absorption spectra of modified low density lipoprotein have suggested substantial differences in the local environments of several aromatic amino acid side chains. Relatively lower ellipticity at 222 nm of modified lipoprotein indicated alterations in the secondary structures of its protein moiety. Nucleophilic reaction of methylamine did not cause the peptide bond scission but it brought conformational transition such that some of the buried hydrophobic domains of the protein moiety got exposed to the aqueous environment. PMID- 1592418 TI - Role of rusticyanin in the electron transport process in Thiobacillus ferrooxidans. AB - Effect of diethyl dithiocarbamate (DEDC), an antimicrobial agent, on growth of Thiobacillus ferrooxidans, possibly by inhibiting rusticyanin present in the periplasmic space of the microorganism, has been studied to gain more insight into the electron transport chain in the bioleaching process. DEDC is found to form a stable complex with rusticyanin in solution and also in polyacrylamide gel. The spectrum of the complex is identical to that of Cu-DEDC complex, suggesting binding of DEDC with copper moiety of rusticyanin and resulting in inhibition of growth. In vitro reduction of purified rusticyanin by Fe(II) in absence of acid-stable cytochrome c is very slow, indicating the importance of cytochrome c in electron transport. Thus, in the iron oxidation process, acid stable cytochrome c is the primary acceptor of electron, transferring the electron to rusticyanin at pH 2.0, which, in turn, affects electron transfer to iron-cytochrome c reductase around pH 5.5. PMID- 1592419 TI - Biochemical analysis of jejunal brush border membrane of golden hamster: pathogenic modulations due to ancylostomiasis. AB - The common hookworm (Ancylostoma ceylanicum) infection of humans was studied in golden hamsters model system. Significant biochemical modulations were observed in hamster jejunal brush border membrane (BBM), the primary site of infection. Analysis of BBM at the peak of infection (3-weeks) revealed a marked decrease in the activities of sucrase, lactase and maltase, while activities of alkaline phosphatase, (Ca2+ + Mg2+)-ATPase and gamma-glutamyl transpeptidase were increased. Kinetic studies conducted with maltase, a superficially localised enzyme of jejunal BBM, revealed loss of enzyme active site during the infection. Among other constituents, the levels of cholesterol and triglycerides were significantly decreased with slight increase in phospholipid content in the infected animals. The hookworm infection also caused a decline in total hexose content indicating an altered membrane glycocalyx. Conversely, there was significant enhancement of hydroxyproline and sialic acid contents. SDS-PAGE analysis showed an enhancement in both low and high molecular weight proteins in jejunal BBM preparations of the infected group. Gel electrophoresis of glycoproteins further revealed the appearance of two additional peaks in the low molecular weight region and concomitant disappearance of a peak in the high molecular weight region. These results strongly support the view that the hookworm infection causes severe damage not to the site of attachment alone but also to the entire cell lining of the jejunum and therefore could influence overall digestion and absorption. PMID- 1592420 TI - Comparative studies on the properties of glycogen phosphorylases from the foot muscles of two benthic bivalves, Sunetta scripta and Villorita cyprenoides, having different habitats. AB - Glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate-alpha-D-glucosyl transferase, EC 2.4.1.1) was partially purified from two bivalves found in different habitats, viz. Villorita cyprenoides, an estuarine bivalve, and Sunetta scripta, a marine bivalve, and their properties compared with other animal phosphorylases. While the kinetic mechanism was same as that of phosphorylases from other animal sources, it differed in the control mechanism from other phosphorylases. The observed differences support the earlier finding that the control mechanism adopted by different animals is dependent on the evolutionary status and energy needs. PMID- 1592421 TI - Relationship of single-stranded DNA-binding proteins of Ehrlich ascites tumour to cell growth phase and DNA replications. AB - The possible involvement of SSB-proteins in DNA replication in Ehrlich ascites tumour (EAT) has been investigated. A direct relation (the computer-generated correlation coefficient was 0.9) between the SSB-proteins content in chromatin and intensity of the replicative synthesis of DNA in various preparation of EAT in vivo and in vitro is observed. Addition of exogenous SSB-proteins to the permeable EAT cells has been found to increase the replicative synthesis. Although eukaryotic SSB-proteins are not complete analogs of the prokaryotic SSB proteins, they evidently participate in DNA replication in eukaryotic cells and possibly are intracellular regulators of proliferation. PMID- 1592422 TI - Regulation of hordein synthesis in barley high lysine mutant Notch-2. AB - Genomic DNA isolated from barley cv. NP 113 and its high lysine mutant Notch-2, and restricted with different restriction enzymes was hybridized with B1 and C hordein DNA probes. Similar Southern hybridization patterns were observed between NP 113 and Notch-2. Dot blot hybridization analysis of RNA isolated at different developmental stages and from different tissues of seed showed temporal as well as tissue specific expression. The results obtained indicate that regulation at the level of transcription/post transcription may be responsible for lower accumulation of hordein in mutant Notch-2. PMID- 1592423 TI - Class II MHC molecules and monocytes/macrophages in the respiratory system of conventional, germ-free and interferon-gamma-treated rats. AB - The localization of I-A-like class II major histocompatibility complex (MHC) molecules and cells of the monocyte/macrophage lineage was studied immunohistologically in the trachea and lungs of conventional, specified pathogen free (SPF) and germ-free rats. In the three groups of animals I-A-like class II MHC molecules occurred in epithelia of the bronchus-associated lymphatic tissue (BALT), in B lymphocytes, in dendritic-shaped and elongated interstitial cells and in type II pneumocytes. Conventional and SPF rats were distinguished from germ-free animals only by the larger number of class II MHC-positive respiratory epithelial cells in the lower trachea and main bronchi. The distribution of monocytes/macrophages (ED1-positive cells) did not differ between the groups. After systemic treatment of SPF rats with interferon-gamma class II MHC molecules were newly induced in all respiratory epithelia and in the endothelium of large vessels. In addition, interferon-gamma sometimes led to pulmonary infiltration and caused class II-positive activated monocytes to accumulate in medium-sized pulmonary vessels and in alveolar capillaries. It is concluded that the microbial status does not qualitatively alter the distribution of class II MHC molecules and monocytes/macrophages in rat respiratory organs. Interferon-gamma can, however, provoke profound changes. PMID- 1592424 TI - Expression of the ED3 antigen on rat macrophages in relation to experimental autoimmune diseases. AB - Susceptibility to experimental autoimmune diseases (EAD) is rat strain dependent. Susceptible animals are reported to have a defective glucocorticoid response. Although many EAD are regarded as preferentially T cell-mediated, macrophages (M phi) play an important role in several different stages of these diseases. In this study we have investigated the possible effect of the disturbed hypothalamic pituitary (HPA) axis on M phi phenotype. Therefore we studied M phi differentiation in several different rat strains, especially with regard to the M phi specific differentiation antigen as recognized by monoclonal antibody (mAb) ED3. This mAb is, in normal healthy rats, reactive with very restricted M phi subpopulations present in the lymphoid organs only. However, in autoimmune diseased tissues many of the infiltrated M phi are also ED3-positive. It appeared that M phi, in vitro derived from monocytes out of susceptible rat strains, showed a high ED3 expression in contrast to monocyte-derived M phi out of resistant rat strains. This difference in ED3 expression appeared to be T cell mediated. Our results are suggestive for the fact that the impaired HPA-axis in EAD susceptible rat strains affects M phi differentiation. The relevance of the observed differences with respect to disease induction, maintenance, or suppression is discussed and obviously needs further investigation. PMID- 1592425 TI - Autotransplanted jejunum in patients with carcinomas of the head and neck: transport of immunosurveillance against tumor cells? AB - Autologous jejunum, transplanted as a functional replacement immediately after radical dissection of advanced stages of squamous cell carcinomas of the head and neck and subsequently irradiated, was examined by immunohistochemistry (APAAP/PAP technique). Biopsies from 9 patients were taken at the time of transplantation and up to 24 months thereafter (group 1) and from 5 patients only once after transplantation (group 2). Twenty-six monoclonal antibodies (mAbs) were used as surface markers to give an overview about phenotypical changes with respect to T , B- and M phi-antigens. 1) B cells: a general increase of CR2+ (CD21, p less than 0.01) could be noticed after transplantation, immunoglobulin positive cells remained unchanged expect for a significant decrease of IgM+ (p less than 0.01) and IgA1+ (p less than 0.01) cells. 2) The number of T cells (CD3+) showed no significant differences although TcR gamma/delta+ cells decreased (p less than 0.01) in the autotransplant. ICAM-1 (CD54) and IL-2R (CD25) were found on a significant (p less than 0.01) higher number of cells after transplantation. 3) Cells with M/M phi morphology showed increased expression of the Fc gamma receptors (CD64, p less than 0.001; CD32, n.s.; CD16, p less than 0.001), of the complement receptors CR1 (CD35, (p less than 0.001) and CR3 (CD11b, p less than 0.02), of HLA-DQ (p less than 0.01), and of the antigens 25F9 (mature M phi; p less than 0.01) and CD4 (p less than 0.02). Correlation analyses of data obtained from the biopsies of the 14 autotransplanted jejunum cases revealed a CD35+ and a 25F9+ subpopulation of M/M phi. Our findings indicate that despite irradiation autotransplanted jejunum contained cells with immunological capacities. Therefore, the replacement of larynx by autologous jejunum may facilitate not only mechanical but also immunological functions. PMID- 1592426 TI - Effect of Bacillus Calmette-Guerin inoculation on numbers of dendritic cells in bronchoalveolar lavages of rats. AB - Dendritic cells (DC) are present in all lymphoid tissues and are widely distributed in the airway epithelium and lung parenchyma. In this study DC were morphologically and cytochemically identified in normal rat bronchoalveolar lavage (BAL), although in very low percentages. Furthermore, the total population as well as different Percoll density fractions demonstrated poor antigen presenting capacity and even suppressed antigen-specific stimulation by rat splenic DC. In contrast, when an inflammatory response was induced by intratracheal inoculation of Bacillus Calmette-Guerin (BCG), an increase of Ia positive cells, containing high percentages of monocytes and DC (MDC) was found. In BAL, DC increased about 25 times within 48 h after BCG inoculation. These BCG induced BAL cells as well as the different density fractions showed a high antigen-presenting capacity at low concentrations. However, at higher concentrations they were suppressive, except for the highest density fraction which lacked alveolar macrophages (AM). These results indicate that the increased numbers of Ia-positive MDC during an inflammatory reaction are very likely responsible for antigen presentation in vitro. In contrast, AM suppress the antigen-specific T cell proliferation in a concentration dependent manner. PMID- 1592427 TI - Natural cytotoxic cell activity in the snake Psammophis sibilans. AB - Thymocytes, splenocytes and peripheral blood mononuclear cells (PBMC) of the snake Psammophis sibilans consistently killed the human erythroleukemic cells K562 in a 4 h assay as judged by lactate dehydrogenase enzyme release. PBMC and splenocyte natural cytotoxicity (NC) increased proportionally with increase in the effector/target cell ratio. Spontaneous killer cell activity was consistently 2-3 times higher in peripheral blood (PB) than in spleen. On the other hand, thymocytes displayed low, yet detectable, NC. In an attempt to define the cell subpopulation responsible for natural killer (NK) activity, PBMC were depleted of macrophages or B lymphocytes before use in NK cell assays against K562 cells. Depletion of macrophages did not impair NK activity thus suggesting that macrophages do not mediate spontaneous lysis in the present 4 h assay. Conversely, removal of B lymphocytes by panning onto dishes coated with monoclonal antibody against snake Ig significantly reduced, but did not eliminate, PBMC spontaneous cytotoxicity. These data suggest that T, B and perhaps distinct NK cells participate in spontaneous lysis. This suggestion was confirmed by studies of NC in thymus, spleen and PB the year round. Strong NC was detected during spring and autumn when high numbers of leukocytes including T and B cells can be recovered from spleen and PB. Negligible spontaneous cytotoxicity was observed during early and mid-summer and in winter, periods of the year when snakes are thymus-less and contain few T and B cells in peripheral lymphoid organs. These findings, the first to document natural cytotoxic activity in snakes, were discussed in relation to the issue of NK cell identity in vertebrates. PMID- 1592429 TI - Activation of the fifth component of human complement by oxygen-derived free radicals, and by methionine oxidizing agents: a comparison. AB - The fifth component of human complement, C5, was activated by non-enzymical, chemical treatment in either of two ways: 1) by oxidation with a hydroxyl radical (OH.) generating system consisting of H2O2, FeEDTA, and ascorbate, activation product called C5(H2O2); 2) by oxidation with chloramine T, activation product called C5(Cl-T). Evaluating earlier findings, completed by new results, both products were compared. Both products are C5-like in that they are capable of binding C6 and form the nucleus for the cytotoxic complex C5-9. Both differ from C5b, the natural activation product of C5, as they comprise the whole, uncleaved C5 protein, and do not immediately decay when not bound to C6. In both cases the treatment involves oxidation of methionine residues in the C5 protein. However, while chloramine T specifically attacks only methionine, oxidation by the OH. generating system involves other amino acid residues, in addition. This probably explains the lower yield of C5b-like activity after treatment with H2O2, and other quantitative differences between C5(H2O2) and C5(Cl-T). Whereas the generation of C5(H2O2) may be physiologically relevant, C5(Cl-T) may prove to be a suitable object for the study of changes in the C5 molecule essential for its activation. PMID- 1592428 TI - Characterization of antibody responses of local lymph nodes to antigen given under the oral submucosa. AB - We studied the function of submandibular lymph nodes (MLN) in the oral mucosa immune system as compared with that of inguinal lymph nodes (ILN) in the cutaneous one. Primary IgM, IgG and IgA antibody responses in MLN to sheep red blood cells (SRBC) as a model antigen given submucosally occurred more extensively than those in ILN to the antigen injected subcutaneously. Particularly, definite IgA synthesis was seen in MLN but not in ILN. This IgA synthesis was shown to be originated locally in oral submucosal lymphoid tissue or MLN but not in gut-associated lymphoid tissue (GALT). This suggested that the oral mucosal tissue including MLN acts like Peyer's patches in GALT for IgA synthesis. When mice were administered with SRBC and bacterial lipopolysaccharide (LPS) submucosally, the adjuvant effect of LPS was only observed on the capacity of MLN cells for secondary antibody response in vitro. This contrasted to the marked augmentation by LPS of both the primary antibody response in ILN and capacity for in vitro secondary antibody response of ILN cells of mice given SRBC and LPS subcutaneously. The radioactivities detected in the local lymph nodes and other tissues of mice given 51Cr labeled SRBC submucosally or subcutaneously were comparable with each other. MLN, however, contained more Ig+/B220+ B cells and less Thy1+/Ly-1+ T cells than ILN did, and the L3T4/Ly-2 ratio of T cell subpopulations in MLN was lower than that in ILN. Partially corresponding to this observation, the B cell-dependent area was developed more extensively in MLN than in ILN. This difference in cellular composition and organization might in part explain the reason why MLN and ILN display distinct modes of response and sensitivity to the action of LPS. PMID- 1592430 TI - Synthetic peptides from a conserved region of gp120 induce broadly reactive anti HIV responses. AB - In our efforts to identify products that might be used for active immunotherapy in human immunodeficiency virus (HIV) infection, we have studied synthetic peptides derived from the CD4 attachment site of gp120. Two peptides have emerged with particularly interesting properties. The first (B138) is linear and spans the envelope residues 421-438; the second (1005/45) encompasses amino acids 418 445 and is cyclized by way of a disulphide bond joining its terminal cysteines. Both species have been shown to inhibit syncytial formation in a conventional bioassay, B138 being the most efficient. Both peptides elicit high titres of anti peptide antibodies in immunized mice, rabbits and goats, with titres exceeding 1:10(5) in many cases. A substantial portion of this response is directed against gp120 as determined by enzyme-linked immunosorbent assay (ELISA). Analysis by flow cytometry has demonstrated that the antisera are broadly reactive with multiple diverse strains of HIV. The anti-gp120 activity of the anti-peptide antiserum was further confirmed by radioimmuno-precipitation (RIP) assays. Furthermore, RIP analysis and inhibition experiments in a GD4-gp120 binding assay have revealed that anti-peptide sera contain antibodies directed against the CD4 attachment site on gp120 and interfere with this receptor-ligand interaction. PMID- 1592431 TI - Synthesis and regulation of the fourth component of complement (C4) in the human monocytic cell line U937: comparison with that of the third component of complement (C3). AB - Production of the fourth component of complement (C4) by the human monocytic cell line U937 and its regulation were investigated in comparison with the production of the third component of complement (C3) in a cell culture system. Although no detectable C4 was produced by U937 without stimulation, U937 was induced by recombinant interferon-gamma (IFN-gamma) to synthesize C4 in a dose- and time dependent fashion. The production of C4 was reversibly inhibited by cycloheximide, indicating that it resulted from de novo synthesis. The C4 synthesized by U937 cells was functionally active as assessed by haemolytic assay. SDS-PAGE following biosynthetic labelling showed that subunit structure of C4 synthesized by U937 cells was identical with that of plasma C4 but that molecular weight of alpha-chain was greater than that of plasma C4. We compared the regulation of C4 synthesis with that of C3 synthesis. Although C3 synthesis by U937 cells was enhanced by IFN-gamma, lipopolysaccharide (LPS) and phorbol myristate acetate (PMA), C4 synthesis was induced only by IFN-gamma. LPS and IFN gamma induced a synergistic increase in C3 synthesis by U937 cells. U937 cells incubated with LPS and IFN-gamma synthesized a greater amount of C4 than those incubated with IFN-gamma alone. Thus it was demonstrated that the synthesis of C3 and C4 was independently regulated. This study shows that the U937 cell line provides a useful model for studies on the synthesis of complement proteins and on the regulation of complement production. PMID- 1592432 TI - The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. AB - The ability of non-ionic surfactant vesicles (NISV) to enhance antibody production against bovine serum albumin (BSA) was compared with Freund's complete adjuvant (FCA), in the BALB/c mouse. Two subcutaneous inoculations with NISV entrapped BSA induced antibody levels comparable to, and persisting as long as those produced by FCA by either the subcutaneous or intraperitoneal route of inoculation. Intraperitoneal inoculation of NISV did not generate as strong an antibody response. The adjuvant activity of NISV was wholly dependent on the BSA being entrapped within preformed vesicles; mixing free BSA with vesicles was not effective. Analysis of the anti-BSA IgG subclasses induced by NISV and FCA showed that NISV were generally better stimulators of IgG2a than was FCA, but poorer stimulators of IgG1. From this, we deduce that NISV are potentially better stimulators of the Th1 lymphocyte subset than is FCA and by inference, potent stimulators of cellular immunity. We believe that NISV may offer many advantages over other adjuvants in terms of immunological selectivity, low toxicity and stability. PMID- 1592433 TI - A monocyte/macrophage antigen recognized by the four antibodies GHI/61, Ber-MAC3, Ki-M8 and SM4. AB - A new monoclonal antibody, GHI/61, which labels the majority of monocytes and tissue macrophages is described. This antibody recognizes an intracellular antigen of 130,000 MW (reduced) and 110,000 MW (unreduced). Using biochemical, flow cytometry and immunocytochemical studies antibody GHI/61 was shown to recognize the same antigen as the previously described antibodies Ber-MAC3, Ki-M8 and SM4. On the basis of the results obtained, antibodies GHI/61, SM4, Ber-MAC3 and Ki-M8 should form a new CD group at the next Leucocyte Typing Workshop. Since the antigen recognized by the antibody GHI/61 is relatively easy to purify, the sequencing and the isolation of the gene encoding this protein should be possible. PMID- 1592434 TI - Properties of human thymic B cells. AB - B cells, distinct from those seen in myasthenia gravis, are present in normal human thymic medulla, concentrated around the Hassall's corpuscles. We have shown that they constitute 33 +/- 4.8% of the total cells in the thymic medulla. In tissue sections they were often seen to have rosettes of thymocytes around them, a relationship which was maintained when the cells were isolated from the thymus. Thymic B cells expressed cytoplasmic immunoglobulins IgD, IgM and IgG but only rarely IgA. Unlike murine thymic B cells, human thymic B cells were CD5-. Freshly isolated thymic B cells were activated cells, but they rapidly became quiescent and died in culture over a 10-day period unless stimulated with mitogens. Thymic B cells responded to polyclonal B-cell activators SAC and TPA and when stimulated, maintained their relationship with thymocytes. Electron microscopic studies showed that two morphologically different thymocyte populations associated with the B cells. The plasma membranes of larger thymocytes were juxtaposed to the B-cell membrane, but smaller thymocytes with darker cytoplasm were associated with the B cells via cytoplasmic strands. Studies in mice have suggested that B cells are involved in thymic negative selection. The close association between activated B cells and thymocytes observed in this study supports this hypothesis. PMID- 1592435 TI - An analysis of the growth and differentiation of B cells isolated from follicles of the ileal Peyer's patch of sheep. AB - We developed a method to isolate and culture cells from the lymphoid follicles of the ileal Peyer's (PP) patch of young sheep (6-12 weeks). These cells were 98% sIgM+ B cells and 1% T cells. Cultured follicular cells were used to investigate B-cell proliferation and differentiation. Less than 50% of B cells were viable after 24 hr of culture and this decrease in B-cell viability also occurred following co-stimulation with pokeweed mitogen (PWM) and recombinant bovine interleukin-1 (rBoIL-1) or rBoIL-2. In contrast, co-stimulation with PWM and either rBoIL-1 or rBoIL-2 induced a marked proliferative response that was maximal on Day 4 of culture. Cytokine-induced proliferation of the B cells required PWM co-stimulation and proliferation induced by rBoIL-1 and rBoIL-2 was neither additive or synergistic. This suggests that PWM bound a molecule or molecules that signalled responsiveness to both rBoIL-1 and rBoIL-2. Culture of follicular cells with PWM and both rBoIL-1 and rBoIL-2 also resulted in B-cell differentiation. This differentiation was associated with decreased proliferation, an increased number of viable B cells, and increased expression of both surface IgM and non-Ig membrane molecules. Thus, co-stimulation of ileal PP follicular cells with PWM and rBoIL-1 and rBoIL-2 resulted in both B-cell proliferation and differentiation. PMID- 1592436 TI - Primary antigen-specific T-cell proliferative responses following presentation of soluble protein antigen by cells from the murine small intestine. AB - To understand the local immune events which occur when a novel antigen is encountered in the gut it is necessary to know whether cells from the mucosal tissues are capable of initiating T-cell reactivity. We have examined the capacity of cells isolated from the Peyer's patches and the lamina propria of the murine small intestine to present keyhole limpet haemocyanin (KLH) to naive syngeneic splenic T cells in vitro. The properties of the gut antigen-presenting cells (APC) were compared with those of cells from the spleen and the mesenteric lymph nodes. Results clearly demonstrate that cells from the lamina propria as well as from the Peyer's patches, mesenteric lymph node and spleen can present KLH to naive T cells, inducing strong proliferative reactions comparable in magnitude and kinetics. All the APC populations tested induced interleukin-2 (IL 2) production in primary cultures, although minor differences were noted when lamina propria cells were used as APC. IL-4 was not detected in supernatants from cultures of non-immune T cells in the presence of APC from any tissue. Phenotypic analysis of the cells in cultures of naive T cells, with antigen and APC from different gut-associated tissues revealed important differences. Cells from Peyer's patch, mesenteric lymph node and spleen gave rise to cultures containing largely CD4+CD8- cells. However, cultures in which lamina propria cells acted as APC consisted primarily of CD4-CD8+ cells. PMID- 1592437 TI - Ageing compromises gastrointestinal mucosal immune response in the rhesus monkey. AB - Most research on the effects of ageing on gut mucosal immunity has been performed using rodents. However, there are inherent difficulties in the extrapolation of rodent data to humans. This study was initiated to define age-related changes in the gastrointestinal (GI) mucosal immune response in non-human primates. Antibody responses were measured in young and old rhesus monkeys (Macaca mulatta) immunized intraduodenally with cholera toxin (Ctx)/cholera toxoid (Ctd). Antigen specific immunoglobulin A (IgA) antibody levels were markedly lower while anti Ctx IgG and IgM titres were higher in the intestinal lavage samples of old as compared to young animals. Total IgA concentrations in gut lavage were independent of age or immune status. Measurable titres of anti-Ctx IgA in the saliva of both age groups support the common mucosal immune hypothesis. Flow cytometric analysis was used to identify age-related shifts in the expression of cell surface antigens on peripheral blood lymphocytes. The relative number of both IgA+ and Ctx+ cells was dramatically reduced in the blood of old monkeys. Collectively, these data suggest that the GI mucosal immune response to Ctx is compromised in old rhesus macaques. The deficit in immune responsiveness, namely reduced anti-Ctx IgA antibody secretion into the intestinal lumen, may be a consequence of alterations in the process of maturation and homing of specific antibody-secreting B lymphocytes. PMID- 1592438 TI - Inhibition of specific T-cell activation by monosaccharides is through their reactivity as aldehydes. AB - The effect of monosaccharides on the inductive interaction between antigen presenting cells and T cells was investigated in a human system. Some monosaccharides, but not others, were found to inhibit antigen-specific T-cell activation. Responses to mitogen were unaffected. In order for inhibition to occur, a high concentration (approximately 50 mM) of monosaccharide was necessary. The role of monosaccharide aldehyde groups in inhibition was investigated using the alpha-methyl pyranoside and the alditol forms of inhibitory monosaccharides. Unlike the native monosaccharides, these molecular configurations possess the ring structure and the open chain structure respectively but do not contain aldehydes. Together they represent all the molecular characteristics of both forms of the monosaccharide except the possession of aldehyde groups. These two molecular species produced no significant inhibition. Modified forms of the sugar moiety of ribofuranosidoadenine (adenosine) were also tested. The periodate oxidized form of the molecule in which the ribose bears two aldehyde groups, was a potent inhibitor of antigen-induced T-cell activation whereas periodate-oxidized, borohydride-reduced ribofuranosidoadenine, in which the ribose aldehydes are converted to alcohols, produced no inhibition. The former was shown to form Schiff bases with ligands on peripheral blood mononuclear cells (PBMC) as predicted whereas the latter did not. Periodate oxidized dextran, but not native dextran, was also inhibitory. Together these data show that inhibition of T-cell activation by sugars requires reactive aldehydes and this is consistent with the Schiff base model of specific antigen-presenting cell (APC)-T cell inductive interaction in which exogenous aldehydes and other carbonyl donors prevent the necessary formation of Schiff bases between cellular ligands. PMID- 1592439 TI - Viral infection induces cytokine release by beta islet cells. AB - Viral infection has been suggested to play a triggering role in the pancreatic beta cell destruction which occurs in insulin-dependent diabetes (IDDM). However, the underlying mechanism of this phenomenon is unknown. In this study a human insulinoma cell line has been infected with measles, mumps and rubella viruses since a temporal association is reported between the clinical onset of IDDM and diseases caused by these viruses. The infection with measles and mumps viruses induced the release of interleukin-1 (IL-1) and interleukin-6 (IL-6) by the cell line as assessed by a bioassay and up-regulated the expression of human leucocyte antigen (HLA) class I and class II antigens as evaluated by cytofluorimetric analysis. Stimulation with rubella virus induced the release of IL-6 only and had no effect on HLA antigen expression. These data show for the first time that IL-1 and IL-6 secretion by an insulinoma cell line may occur after viral infection and suggest that cytokine release and increased expression of HLA molecules by beta cells may act to induce the immune response towards beta cells in IDDM. PMID- 1592440 TI - Molecular analysis of the inhibition of interleukin-8 production by dexamethasone in a human fibrosarcoma cell line. AB - In order to analyse the effects of glucocorticoids on interleukin-8 (IL-8) production more precisely, we examined the effects of dexamethasone on IL-8 production at the molecular level in a human fibrosarcoma cell line, 8387, which IL-1 induces to express IL-8 messenger RNA (mRNA) and to secrete IL-8. Over a wide dose range, dexamethasone inhibited IL-8 production induced by IL-1 alpha stimulation. Northern blotting analysis showed that dexamethasone also inhibited the IL-8 mRNA accumulation in a similar dose-related manner. Nuclear run-off assay revealed that dexamethasone decreased the transcription of the IL-8 gene and the degree of inhibition of transcription correlated well with the inhibition of IL-8 production, suggesting that the action of glucocorticoids is mainly at the transcriptional level. Furthermore, transfection with chloramphenicol acetyl transferase (CAT) expression vectors inserted with the 5'-deleted IL-8 gene demonstrated that the 5'-flanking region which contains the glucocorticoid response element (GRE) was mainly involved in the dexamethasone-induced repression of the IL-8 gene. These data suggest that the inhibition of the IL-8 gene transcription by glucocorticoids occurs through the interaction of the glucocorticoid receptor complex with GRE in the 5'-flanking region of the IL-8 gene. PMID- 1592441 TI - A crucial role of the thymus in induction by the lprcg gene of lymphadenopathy with autoimmunity in the mouse. AB - The new mutation at the lpr locus, lprcg, induces massive lymphoproliferation characterized by the selective expansion of CD4-, CD8-, B220+, Thy-1+ cells or double-negative T lymphocytes and production of autoantibodies as does lpr. The thymus is necessary for the induction of anomalous double-negative T lymphocytes and autoimmune symptoms by lpr. To determine whether or not the thymus is also indispensable to expression of the function of lrpcg, lprcg homozygous athymic nude mice (lprcg/lprcg nu/nu; lprcg nudes) were constructed by crossing CBA/KlJms lprcg/lprcg (CBA-lprcg) and DDD/l-nu/nu mice and observed for lymphoid organ hyperplasia and autoantibody production with or without thymus grafts from various strains of mice including CBA-lprcg. Neither lymphoproliferation nor significantly increased production of autoantibodies was observed in unmanipulated lprcg nudes. In contrast, thymus grafts of both +/+ and lprcg/lprcg genotypes caused lymphoid organ hyperplasia composed of anomalous double-negative T lymphocytes and significantly augmented the production of antibodies against single-stranded DNA (ssDNA). Interestingly, serum Ig and anti-ssDNA antibody levels rose in response to thymus grafts only in IgG but not in IgM classes. These results indicate that the thymus plays a crucial role in the induction of abnormal T-cell differentiation by lprcg and that thymic genotype is irrelevant. PMID- 1592442 TI - Adoptive transfer of the generalized lymphoproliferative disease (gld) syndrome in nude beige mice. AB - C57BL/6 nude beige mice (B6 nubg) were used as recipients for the transfer of haematopoietic cells from either B6 wild as control mice, or systemic lupus erythematous B6 mice homozygous for the recessive generalized lymphadenopathy disease (gld) locus. Both gld and wild cell grafts prolonged survival of the short-living B6 nubg recipients and restored some T-cell functions, as monitored by the presence of T-dependent Ig isotypes in the serum and responsiveness of spleen cells to a T-cell mitogen. Moreover, the [gld----nubg] chimeras but not the [wild----nubg] chimeras showed several similarities with gld control mice, particularly, a spleen and lymph node hyperplasia, elevated anti-single-stranded DNA antibody titres and a hyperglobulinaemia. This hyperglobulinaemia was however qualitatively different from the gld-type hyperglobulinaemia with an important contribution of the IgG1 isotype; the lymph node hyperplasia was also less marked than in B6 gld mice. PMID- 1592443 TI - Expression of activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL 2R alpha) and IL-2R beta on T cells of human decidua at an early stage of pregnancy. AB - T cells of human decidua at an early stage of pregnancy were examined by flow cytometry for the expression of the T-cell-activation antigens CD69, HLA-DR, interleukin-2 receptor-alpha (IL-2R alpha) and IL-2R beta. The decidua contained a small number of T cells and both CD4+ and CD8+ subsets expressed CD69, HLA-DR, IL-2R alpha and IL-2R beta antigens significantly whereas, in peripheral blood, only a small number of T cells expressed these activation antigens. These findings indicate that T cells in the decidua in the first trimester of pregnancy are regionally activated. PMID- 1592444 TI - The influence of the In(Lu) gene on expression of CDw75 antigens on human red blood cells. AB - The influence of the In(Lu) gene on human red blood cell (RBC) expression of CDw75 antigens was examined. CDw75 antigens were increased in expression on Lu(a b-) cells of the dominant inhibitor type in comparison with red cells from donors of other Lutheran (Lu) phenotypes. In contrast, CD44 epitopes detected with F10 44-2, A3D8 and BU52 monoclonal antibodies (mAb) were decreased in expression on Lu(a-b-) red cells. Among normal blood donors of the common phenotype Lu(a-b+) there was a wide range of expression of CDw75 antigens on red cells. The results show that CDw75 is a quantitative polymorphism of human red cells and, among antigens influenced by the In(Lu) gene, is unique in being up-regulated in expression. PMID- 1592445 TI - Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. AB - The purpose of the present study was to assess the prevalence of orthostatic hypotension and its associations with demographic characteristics, cardiovascular risk factors and symptomatology, prevalent cardiovascular disease, and selected clinical measurements in the Cardiovascular Health Study, a multicenter, observational, longitudinal study enrolling 5,201 men and women aged 65 years and older at initial examination. Blood pressure measurements were obtained with the subjects in a supine position and after they had been standing for 3 minutes. The prevalence of asymptomatic orthostatic hypotension, defined as 20 mm Hg or greater decrease in systolic or 10 mm Hg or greater decrease in diastolic blood pressure, was 16.2%. This prevalence increased to 18.2% when the definition also included those in whom the procedure was aborted due to dizziness upon standing. The prevalence was higher at successive ages. Orthostatic hypotension was associated significantly with difficulty walking (odds ratio, 1.23; 95% confidence interval, 1.02, 1.46), frequent falls (odds ratio, 1.52; confidence interval, 1.04, 2.22), and histories of myocardial infarction (odds ratio, 1.24; confidence interval, 1.02, 1.50) and transient ischemic attacks (odds ratio, 1.68; confidence interval, 1.12, 2.51). History of stroke, angina pectoris, and diabetes mellitus were not associated significantly with orthostatic hypotension. In addition, orthostatic hypotension was associated with isolated systolic hypertension (odds ratio, 1.35; confidence interval, 1.09, 1.68), major electrocardiographic abnormalities (odds ratio, 1.21; confidence interval, 1.03, 1.42), and the presence of carotid artery stenosis based on ultrasonography (odds ratio, 1.67; confidence interval, 1.23, 2.26). Orthostatic hypotension was negatively associated with weight. We conclude that orthostatic hypotension is common in the elderly and increases with advancing age. It is associated with cardiovascular disease, particularly those manifestations measured objectively, such as carotid stenosis. It is associated also with general neurological symptoms, but this link may not be causal. Differences in prevalence of and associations with orthostatic hypotension in the present study compared with others are largely attributed to differences in population characteristics and methodology. PMID- 1592446 TI - Relation of central hemodynamics to obesity and body fat distribution. AB - Central obesity increases the risk for cardiovascular disease, but little is known about its hemodynamic effects. The aims were to investigate the influence of obesity (as defined by body mass index) and abdominal fat accumulation (as defined by the waist/hip ratio) on hemodynamics at rest and during mental stress. Invasive hemodynamic studies were performed in 20 healthy, normotensive young men (aged 18-22 years) recruited from an unbiased population sample. Their body mass index and waist/hip ratio ranged between 18.5 and 30.2 (mean 24.1) and 0.77 and 0.98 (mean 0.87), respectively. Hemodynamics were related to the two anthropometric indexes by bivariate regression analyses. Cardiac output and stroke volume were positively correlated to body mass index (p = 0.05 and p = 0.005), but inversely to waist/hip ratio (p = 0.01 and p = 0.01). Mental stress augmented the hemodynamic patterns. Total peripheral resistance during stress correlated inversely to body mass index (p = 0.02), whereas high waist/hip ratio was associated with higher systemic vascular resistance p = 0.002). The delta CO/delta MAP ratio, i.e., relative contribution of cardiac output for the stress induced increase in mean arterial pressure, showed a strong positive association with body mass index (p = 0.004), but was inversely related to the waist/hip ratio (p = 0.002). Serum insulin correlated significantly to the stress-induced change in total peripheral resistance (r = 0.54; p = 0.02), whereas the increase in cardiac output was inversely related to insulin (r = -0.59; p = 0.007). Thus, central obesity is associated with a specific hemodynamic pattern characterized by higher total peripheral resistance, lower cardiac output, and a vasoconstrictor response to psychosocial stress. PMID- 1592448 TI - Effects of sodium salts on pressor reactivity in salt-sensitive men. AB - Blood pressure in patients with essential hypertension is raised by sodium chloride but not by nonchloride sodium salts. Although a high sodium chloride diet is known to augment the pressor response to norepinephrine and angiotensin II, the effect of nonchloride sodium salts on pressor responsiveness has not been studied so far. To examine whether sodium chloride and nonchloride sodium salts evoke different pressor responses to these agonists, we performed graded norepinephrine and angiotensin II infusions in salt-sensitive (n = 7) and salt resistant (n = 8) normotensive subjects. The subjects were given a low salt diet (20 mmol/day) for 3 weeks, to which a supplement of 200 mmol sodium per day, provided as either sodium chloride or sodium citrate, or a placebo was added for 1 week each. We found that, although sodium chloride raised mean arterial blood pressure in the salt-sensitive subjects (p less than 0.005), sodium citrate did not. However, under both sodium salts pressor response to norepinephrine and angiotensin II was significantly greater than under placebo (p less than 0.02). Furthermore, with both sodium salts, pressor response in the salt-sensitive subjects was greater than in the salt-resistant subjects (p less than 0.01). This study thus demonstrates that, although blood pressure in salt-sensitive individuals is raised by sodium chloride only, both sodium chloride and sodium citrate evoke similar increases in pressor response to norepinephrine and angiotensin II. Since pressor response increased with both sodium salts but resting blood pressure increased only with sodium chloride, enhanced pressor responsiveness alone cannot account for the sodium chloride-induced rise in resting blood pressure. PMID- 1592447 TI - Disturbed calcium metabolism in offspring of hypertensive parents. AB - To assess a possible heritability of a disturbed calcium metabolism in relation to blood pressure regulation, 28 young normotensive offspring of either hypertensive or normotensive parents were studied while administered a defined diet with daily sodium chloride of 6 and 20 g/day for 7 days each. Before the high salt diet was begun, the cytosolic calcium concentration ([Ca2+]i) in platelets was elevated in offspring of hypertensive parents, whereas serum electrolytes, plasma renin activity, plasma catecholamines, and 24-hour urinary excretion of sodium and calcium showed no difference between the two groups. On exposure to a high salt diet, the mean blood pressure increased (from 80 +/- 2 to 85 +/- 2 mm Hg, p less than 0.05) in offspring of hypertensive parents. These changes in mean blood pressure were positively correlated with the basal platelet [Ca2+]i (r = 0.61, p less than 0.01), whereas [Ca2+]i did not demonstrate any significant changes. When the subjects were administered the high salt diet, plasma ionized calcium decreased (from 2.37 to 2.21 meq/l, p less than 0.05) and 1,25-dihydroxyvitamin D3 increased (from 32.7 to 40.8 pg/ml, p less than 0.05) with a transient relative hypercalciuria in offspring of hypertensive parents. This increase of 1,25-dihydroxyvitamin D3 was significantly correlated with the changes in mean blood pressure (r = 0.62, p less than 0.01). Disturbed intraplatelet and systemic calcium metabolism may be of predictive value in the development of hypertension. PMID- 1592449 TI - Salt-dependency of endothelin-induced, chronic hypertension in conscious rats. AB - The effect of salt intake on the hypertensive response to long-term infusion of endothelin-1 was investigated. Chronically instrumented male Sprague-Dawley rats (325-375 g) were used in a 15-day protocol that included 3 control days followed by 7 days of endothelin-1 infusion at 5.0 pmol.kg-1.min-1 and 5 days of recovery. Rats were maintained on either a normal sodium chloride intake (2.0 meq Na+ per day; normal sodium) or a high sodium chloride intake (6.0 meq Na+ per day; high sodium) throughout the protocol. Control rats received normal or high sodium intakes but not endothelin-1. In high-sodium rats, endothelin-1 produced a significant increase in mean arterial pressure and total peripheral resistance; a significant bradycardia was observed only on the first day after the start of the endothelin-1 infusion. Cardiac output, stroke volume, water balance, and urinary sodium and potassium excretion remained unchanged. Termination of endothelin-1 infusion resulted in rapid normalization of both arterial pressure and peripheral resistance. In contrast, normal sodium rats exhibited no alteration in mean arterial pressure, heart rate, total peripheral resistance, stroke volume, water balance, or urinary sodium and potassium excretion throughout the endothelin-1 infusion protocol. The hypertension produced by endothelin-1 infusion cannot be explained by alterations in salt or water balance since endothelin-1 infusion in high sodium animals produced significant increases in mean arterial pressure with no observable changes in water or electrolyte balance. These results indicate that endothelin-induced hypertension in conscious rats is a salt-dependent model of hypertension. PMID- 1592450 TI - Repetitive, episodic hypoxia causes diurnal elevation of blood pressure in rats. AB - An association between chronic high blood pressure and obstructive sleep apnea has been described. We hypothesized that repetitive episodic hypoxia patterned after the hypoxia seen in sleep apnea could contribute to diurnal elevation of blood pressure. Using 12-second infusions of nitrogen into daytime sleeping chambers, four groups of male rats (250-375 g) were subjected to intermittent hypoxia (3-5% nadir ambient oxygen) every 30 seconds, 7 hours per day for up to 35 days. In one group, blood pressure was measured weekly by the tail-cuff method in conscious animals during 5 weeks of episodic hypoxia. In the other three groups, blood pressure was measured in conscious animals via femoral artery catheters at baseline and after 20, 30, or 35 days of exposure. Additional groups served as controls: two sham groups housed in identical "hypoxia" chambers received compressed air instead of nitrogen (35 days) while two other groups remained unhandled in their usual cages (35 days). Both groups challenged with 35 days episodic hypoxia showed significant increases in blood pressure compared with controls: the tail-cuff rats showed a 21 mm Hg increase in systolic pressure (p less than 0.05) and the intra-arterially measured rats a 13.7 mm Hg increase in mean arterial pressure (p less than 0.05). The 30-day exposed rats also showed a 5.7 mm Hg increase in mean pressure over baseline (p less than 0.05). Blood pressure did not change significantly from baseline in the control groups. Left ventricle-to-body weight ratio was higher in both 35-day exposed groups than in unhandled or sham controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592451 TI - Arterial chemoreceptor reflex and hypertension. PMID- 1592452 TI - Pressor responsiveness in corticosteroid-induced hypertension in humans. AB - In previous studies short-term cortisol increased cold pressor responses and the rise in forearm vascular resistance accompanying intra-arterial norepinephrine without an increase in overall resting sympathetic nervous activity. The present study examined whether these alterations in pressor response are glucocorticoid or mineralocorticoid effects, or both. Normal male subjects (n = 12) received either fludrocortisone, 0.3 mg daily (n = 6), or dexamethasone, 3 mg daily (n = 6), for 7 days. Hemodynamic studies were performed before and on day 7 of treatment. Fludrocortisone increased body weight from 69.3 +/- 1.8 to 71.1 +/- 2 kg (p less than 0.001), cardiac output from 5.0 to 6.0 l/min (+/- 0.1, p less than 0.01), mean arterial pressure from 82 +/- 1 to 91 +/- 1 mm Hg (p less than 0.001), cold pressor responsiveness from 13.0 to 39.0 mm Hg/ml per 100 ml per minute (R units) (+/- 4.3, p less than 0.01), and forearm vascular response to intra-arterial norepinephrine (F = 59.4, p less than 0.01) and angiotensin II (F = 30.8, p less than 0.01) infusions. Total peripheral resistance fell from 22.0 to 20.1 mm Hg/l per minute (+/- 0.3, p less than 0.05). Dexamethasone did not increase cardiac output, 5.1 to 5.2 l/min (+/- 0.1), or body weight but did increase mean arterial pressure from 82 +/- 3 to 91 +/- 3 mm Hg (p less than 0.001), cold pressor responsiveness from 8.6 to 17.1 R units (+/- 2.8, p less than 0.05), and forearm vascular response to intra-arterial norepinephrine (F = 33.0, p less than 0.01) and angiotensin II (F = 54.9, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592453 TI - Altered dopaminergic responses in hypertension. AB - Biogenic amine metabolism may be altered in hypertension and thus contribute to its pathophysiology. This report describes an abnormality in dopamine excretion in hypertensive subjects in the postabsorptive state that persists despite an increase in dietary precursors for dopamine supplied by a protein meal. We studied seven normotensive and six nonmedicated hypertensive men after two different meals: 60 g protein and a noncaloric electrolyte-equivalent broth. Overall mean sodium excretion was 56% higher in the hypertensive group throughout both meal studies (p less than 0.01), implying higher chronic dietary sodium intake. Despite this, overall urinary excretion of dopamine tended to be lower in hypertensive than in normotensive subjects (p = 0.06). Hypertensive also differed from normotensive subjects in their response to protein feeding. In the normotensive subjects there was a 23% increase in urinary dopamine excretion (p less than 0.05), which was not seen after the noncaloric meal. In the hypertensive subjects, there was no change in urinary dopamine after the protein meal. In the normotensive subjects there was a 74% increase in sodium excretion (p less than 0.01) after the protein meal, but no significant change was seen in the hypertensive subjects. There were no differences in baseline renal plasma flow or glomerular filtration rate between the groups and no statistically significant differences between the groups in their renal hemodynamic responses to the meals. In summary, hypertensive subjects have less renal dopamine production for the amount of sodium ingested and a decreased renal dopamine production in response to a protein load as compared with normotensive subjects, consistent with a renal defect in conversion of DOPA to dopamine. PMID- 1592454 TI - A new model for diurnal blood pressure profiling. Square wave fit compared with conventional methods. AB - For the characterization of diurnal blood pressure variation, we developed a simple mathematical model that nevertheless does justice to the specific form characteristics of individual blood pressure registrations. Analysis was based on 24-hour continuous intra-arterial measurement of blood pressure obtained in 23 hospitalized patients with mild-to-moderate untreated essential hypertension (mean +/- SD, 112 +/- 13 mm Hg). The day-night difference for mean arterial pressure varied markedly (mean, 18.6 mm Hg; range, 6.8-36.0). Inspection of profiles suggested a model of blood pressure as two contiguous, complementary periods of constant pressure, a so-called square wave. Determination of the times of transience between both periods (segmentation) was performed individually using a least-square error criterion. Results were compared with those obtained by conventional methods, including analysis by Fourier modeling. The square wave fit accounted for a larger fraction (66%) of circadian variance of mean arterial pressure than modeling based on segmentation by visual inspection (59%, considerable observer bias) or by clock time (50%). Application of the Minnesota Cosinor Method resulted in the poorest description (47%). Segmentation based on harmonic modeling (61%) appeared to be cumbersome (10 harmonics needed), and the significance of additional information offered over the square wave fit is dubious. Observer bias makes segmentation by visual inspection unsuitable for assessment of the circadian variance of blood pressure. Even when daily activities are strictly regulated (hospital environment), circadian variance is not well modeled by clock time. As compared with harmonic analysis, square wave fitting is simple, and it appears to best model the circadian variance. The method can also be applied to data obtained from noninvasive ambulatory blood pressure monitoring. PMID- 1592455 TI - Influence of short-term blood pressure variability on blood pressure determinations. AB - To evaluate the effect of blood pressure variability on Riva Rocci Korotkoff blood pressure determinations, we studied the intra-arterial pressure during Riva Rocci Korotkoff determinations in 25 patients. In 50 measurements with a cuff deflation rate of 2.5 mm Hg/sec, the systolic intra-arterial pressure at Korotkoff phase 1 was 2.1 (95% confidence interval 1.2-3.0) mm Hg higher than the average systolic intra-arterial pressure in the 20 seconds surrounding this moment (p less than 0.01). This elevation was shown to increase with increasing blood pressure variability, as expressed by the standard deviation of the systolic blood pressure. The elevation caused by the proposed mechanism was amplified when a slow cuff deflation rate of 1.5 mm Hg/sec was used. No significant difference was noted in the diastolic intra-arterial pressure at Korotkoff phase 5, when a normal deflation rate of 2.5 mm Hg/sec was used. A slow cuff deflation rate caused a small elevation in diastolic pressure at the moment of Korotkoff phase 5. We conclude that even normally occurring blood pressure variability might lead to a consistent elevation of systolic Riva Rocci Korotkoff blood pressure measurements. This effect is reinforced by an increasing blood pressure variability and by a slower cuff deflation rate. PMID- 1592456 TI - Proceedings of the Council for High Blood Pressure Research. Chicago, Illinois, September 24-27 1991. PMID- 1592457 TI - Forearm resistance vessel abnormalities and insulin resistance in obese adolescents. AB - To determine if structural changes in forearm resistance vessels are associated with insulin resistance, we evaluated the relation between minimum forearm vascular resistance and insulin resistance in 95 obese adolescents before and after weight loss. Insulin resistance was assessed by fasting insulin levels and sum of insulin values after an oral glucose tolerance test in all 95 subjects and whole body glucose uptake during euglycemic hyperinsulinemia in 35 of 95 subjects. Structural changes in forearm vessels were assessed by measurement of minimum forearm vascular resistance during 10 minutes of ischemic exercise. As compared with our normal values, obese adolescents had a significantly (p less than 0.01) decreased maximal forearm blood flow (41.6 +/- 1.4 versus 67.1 +/- 2.4 ml/min/100 ml) and increased minimum forearm vascular resistance (2.9 +/- 0.4 versus 1.6 +/- 0.7 mm Hg/ml/min/100 ml). There was a significant relation (p less than 0.01) between minimum forearm vascular resistance and fasting insulin, sum of insulins, and whole body glucose uptake. After a 20-week weight-loss program, minimum forearm vascular resistance decreased (3.0 +/- 0.3 versus 2.0 +/- 0.2, p less than 0.01), maximal forearm blood flow increased (41 +/- 2.3 versus 57.4 +/- 3.9, p less than 0.01), and forearm volume remained unchanged. We also observed a significant (p less than 0.01) relation between the decrease in minimum forearm vascular resistance and the decrease in fasting insulin (r = 0.29), decrease in sum of insulins (r = 0.42), and increase in whole body glucose uptake (r = 0.63).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592458 TI - Insulin increases sympathetic activity but not blood pressure in borderline hypertensive humans. AB - We have previously demonstrated that physiological hyperinsulinemia in normotensive humans increases sympathetic nerve activity but not arterial pressure since it also causes skeletal muscle vasodilation. However, in the presence of insulin resistance and/or hypertension, insulin may cause exaggerated sympathetic activation or impaired vasodilation and thus elevate arterial pressure. This study sought to determine if insulin causes a pressor response in borderline hypertensive humans by producing exaggerated increases in sympathetic neural outflow or impaired vasodilation. We recorded muscle sympathetic nerve activity (microneurography, peroneal nerve), forearm blood flow, heart rate, and blood pressure in 13 borderline hypertensive subjects during a 1-hour insulin infusion (38 microunits/m2/min) while holding blood glucose constant. Plasma insulin rose from 12 +/- 3 microunits/ml (mean +/- SEM) during control to 73 +/- 7 microunits/ml during insulin infusion and fell to 9 +/- 2 microunits/ml 2 hours after insulin infusion was stopped. Muscle sympathetic nerve activity, which averaged 25 +/- 2 bursts per minute in control, increased significantly during insulin infusion (+9 bursts per minute) and remained elevated 1.5 hours into recovery (+7 bursts per minute, p less than 0.001). Despite increased muscle sympathetic nerve activity, there were significant (p less than 0.001) increases in forearm blood flow and decreases in forearm vascular resistance during insulin infusion. Further, systolic and diastolic pressures fell approximately 3 and 6 mm Hg, respectively, during insulin infusion (p less than 0.01). This study suggests that acute physiological increases in plasma insulin elevate sympathetic neural outflow in borderline hypertensive humans but produce vasodilation and do not elevate arterial pressure. PMID- 1592459 TI - Plasma norepinephrine responses to head-up tilt are misleading in autonomic failure. AB - The failure of plasma norepinephrine to rise during upright posture is accepted as a diagnostic sign of autonomic nervous failure in patients with postural hypotension. Our clinical experience has been that this test is misleading, with an increase in plasma norepinephrine commonly occurring. To test whether this might result from absent reflex postural venous constriction lowering cardiac output and plasma norepinephrine clearance, we measured norepinephrine plasma kinetics during recumbency and 30 degrees head-up tilting in six patients with pure autonomic failure and eight healthy subjects. Mean arterial pressure fell by 54 +/- 8 mm Hg with head-up tilt in the patients with pure autonomic failure. The plasma norepinephrine concentration (arterial sampling) increased 73 +/- 29 pg/ml (mean difference +/- SED, p less than 0.02), solely because of a 36% reduction in the clearance of norepinephrine from plasma (0.78 +/- 0.09 l/min, p less than 0.0001). In normal subjects, plasma norepinephrine concentration rose by 112 +/- 20 pg/ml (p less than 0.001), largely because of a 24% increase in norepinephrine spillover to plasma (190 +/- 20 ng/min, p less than 0.005). When the postural fall in blood pressure and cardiac output in the pure autonomic failure patients was prevented by the selective venoconstrictor dihydroergotamine (10 micrograms/kg i.v.), no fall in plasma clearance or rise in plasma concentration of norepinephrine occurred. Measurement of the change in plasma norepinephrine with postural stimulation in patients with orthostatic hypotension is not a reliable diagnostic test for autonomic failure because elevations can occur in the plasma concentration that are entirely attributable to reduced plasma norepinephrine clearance. PMID- 1592460 TI - Defective dopamine generation from dihydroxyphenylalanine in stable essential hypertensive patients. AB - We studied the metabolic pathways of dihydroxyphenylalanine (DOPA) and dopamine as well as the cardiovascular and renal responses to a single administration of DOPA (500 mg orally) in stable essential hypertension. We found that after DOPA, stable hypertensive patients compared with controls showed more blood pressure decrease without reflex tachycardia, had lower creatinine clearance but a higher fractional excretion of sodium, and had lower plasma renin activity at the height of DOPA action. Hypertensive patients also showed increased plasma DOPA, the ratio of plasma DOPA to dopamine, and the sum of plasma DOPA and 3-O-methyl-DOPA, as well as increased urinary 3-O-methyl-DOPA and the plasma and urine dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid. Finally, despite an augmented post-DOPA glomerular load of DOPA, the predominant source of urinary dopamine, the excretion rates of dopamine and its metabolites remained comparable in hypertensive patients to those in control subjects. These data suggest that, in stable hypertensive patients, exogenous DOPA is to a lesser degree decarboxylated to dopamine, which is more rapidly metabolized intraneuronally. Contrasting with this finding are the hyperdopaminergic features, such as hypernatriuresis with renin suppression and excessive blood pressure decline in the absence of reflex tachycardia. They may be due to an upregulation of renal, vascular, and brain dopaminergic receptors secondary to a preexisting dopaminergic deficiency in stable essential hypertension. PMID- 1592461 TI - Differential modulation by mu- and delta-opioids on baroreceptor reflex in conscious rabbits. AB - We examined the role of central mu- and delta-opioids on both neurohormonal responses and baroreceptor reflex in conscious rabbits. Both intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-selective agonist, and [D-Ala2,D-Leu5]-enkephalin, a delta-selective agonist, caused dose related increases in arterial pressure and renal sympathetic nerve activity, whereas intravenous injection of the same maximum dose of these peptides as that used in the intracerebroventricular experiment did not cause any cardiovascular and neuronal responses. On the other hand, increases in plasma epinephrine, norepinephrine, and glucose levels induced by intracerebroventricular [D-Ala2,N Me-Phe4,Gly5-ol]-enkephalin were significantly greater than those by [D-Ala2,D Leu5]-enkephalin. Both enkephalins did not cause any responses in plasma renin activity, plasma vasopressin, and serum sodium and potassium concentrations. The sensitivity of the baroreceptor reflex control of renal sympathetic nerve activity using a logistic model was enhanced by a subpressor dose of intracerebroventricular [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (10 pmol/kg) but not by [D-Ala2,D-Leu5]-enkephalin. Conversely, a mu-selective dose of intravenous naloxone (0.1 mg/kg) attenuated baroreceptor reflex sensitivity. Intravenous naloxone methobromide, which has been shown not to cross the blood-brain barrier, did not change baroreceptor reflex sensitivity, suggesting that naloxone acts at the central nervous system. In conclusion, in conscious rabbits, 1) intracerebroventricular mu- and delta-receptor agonists caused pressor responses and 2) mu-opioid agonist altered baroreceptor reflex control of renal sympathetic nerve activity and produced changes in sympathoadrenal responses. PMID- 1592462 TI - Cardiac parasympathetic hyperresponsiveness in spontaneously hypertensive rats. AB - The bradycardic response to baroreceptor stimulation is impaired in human and experimental hypertension. Because this bradycardia mainly depends on the vagus, this may reflect a reduced cardiac parasympathetic responsiveness, which would parallel the reduced cardiac adrenergic responsiveness observed in hypertension. To test this hypothesis, 12-week-old spontaneously hypertensive rats (n = 12) and normotensive Wistar-Kyoto rats (n = 11) were anesthetized with ketamine and underwent bilateral vagotomy. Cardiac parasympathetic responsiveness was assessed from the bradycardia induced by 1) graded electrical stimulation of the right efferent vagus (1-16 Hz) and 2) graded intravenous injections of methacholine (1 8 micrograms.kg-1). The slope of the linear regression between the bradycardiac response and the applied stimulus was taken as the measure of cardiac parasympathetic responsiveness. To identify the onset of possible alterations in cardiac parasympathetic responsiveness in hypertension, the study was extended to younger (8-week-old) spontaneously hypertensive (n = 11) and Wistar-Kyoto (n = 13) rats. With vagal stimulation, cardiac parasympathetic responsiveness was greater in 12-week-old spontaneously hypertensive rats than in 12-week-old Wistar Kyoto rats (24.8 +/- 5.4 versus 10.1 +/- 1.2 beats per minute per hertz, mean +/- SEM, p less than 0.035). This was also the case with methacholine (18.8 +/- 3.5 versus 13.1 +/- 4.4 beats per minute per microgram per kilogram, p less than 0.045). In contrast, cardiac parasympathetic responsiveness was similar, with both vagal stimulation and methacholine, when tested in the younger spontaneously hypertensive and Wistar-Kyoto groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592463 TI - Salt-dependent hypertension in the sinoaortic-denervated rat. AB - To determine the extent to which baroreceptor function is a determinant of salt dependent hypertension, we studied the cardiovascular and renal responses to increasing dietary sodium chloride in sinoaortic-denervated (n = 9) and sham denervated (n = 9) Sprague-Dawley rats. Rats were instrumented with an arterial catheter for measurement of arterial pressure and were individually housed for daily measurements of water intake, sodium intake, urinary output, and urinary sodium excretion. Arterial pressure was monitored daily over a 30-minute period by computer. After 3 days of control measurements (0.4% sodium chloride diet), dietary sodium chloride was increased to 8.0% for 21 days, followed by a 3-day recovery period (0.4% sodium chloride). Ingestion of an 8.0% sodium chloride diet resulted in a 20- to 25-fold increase in sodium intake and a fivefold increase in water intake in both groups. In sinoaortic-denervated rats, arterial pressure increased approximately 10 mm Hg on days 5-10, 20 mm Hg on days 11-18, and 30 mm Hg on days 19-21 of 8.0% sodium chloride. Arterial pressure returned to control levels within the first 24 hours of the recovery period. Elevated sodium intake had no significant effect on arterial pressure in the sham-denervated group. Finally, there were no significant differences between groups in urine output or urinary sodium excretion at any time during the study. We conclude that a primary impairment in the afferent limb of the arterial baroreceptor reflex results in salt-dependent hypertension in the Sprague-Dawley rat. PMID- 1592464 TI - Effect of blocking angiotensin II receptor subtype on rat sympathetic nerve function. AB - This study examined effects of nonpeptide angiotensin II (Ang II) receptor subtype antagonists on the interaction of sympathetic function and Ang II in pithed rats. Effects of spinal cord stimulation (0.5-4 Hz) and norepinephrine (0.3-3 micrograms/kg i.v.) on mean arterial pressure (recorded with a carotid arterial catheter), cardiac output (measured with an electromagnetic flowmeter and flow probe around the thoracic ascending aorta), total peripheral resistance, and heart rate were determined. The subtype 1-selective Ang II receptor antagonist losartan (previously known as DuP 753) at 10 mg/kg i.v. blocked the hemodynamic responses to Ang II at 1 microgram/kg i.v. It inhibited mean arterial pressure and total peripheral resistance responses but not cardiac output and heart rate responses to spinal cord stimulation. In contrast, it reduced mean arterial pressure and cardiac output responses but not total peripheral resistance and heart rate responses to intravenous norepinephrine. Given at 100 mg/kg i.v., the subtype 2-selective receptor antagonist PD123177 did not reduce hemodynamic responses to intravenous Ang II, spinal cord stimulation, and intravenous norepinephrine. These results suggest that endogenous Ang II facilitates the release of norepinephrine from sympathetic nerve terminals in the vasculature of pithed rats. Similar to the Ang II receptor in vascular smooth muscle, the prejunctional Ang II receptor in pithed rats appears to be of subtype 1. PMID- 1592465 TI - Central DuP 753 does not lower blood pressure in spontaneously hypertensive rats. AB - Oral administration of the angiotensin II receptor subtype 1 (AT1) antagonist DuP 753 causes long-lasting lowering of mean arterial pressure in spontaneously hypertensive rats. We examined whether the antihypertensive action of DuP 753 is a result of inhibition of brain angiotensin II. In normal spontaneously hypertensive rats, we found that intracerebroventricular DuP 753 (10 micrograms) blocked the pressor action of intracerebroventricular angiotensin II (100 ng); however, intracerebroventricular DuP 753 (10 micrograms) had no effect on the pressor response to 300 ng/kg angiotensin II administered intravenously (48 +/- 3 mm Hg in the presence of intracerebroventricular DuP 753 versus 49 +/- 4 mm Hg in its absence). In both normal and furosemide-treated spontaneously hypertensive rats (low Na+ diet plus furosemide), intracerebroventricular DuP 753 alone at 10 or 100 micrograms caused transient but significant pressor responses; however, no significant reduction in pressure (versus controls) was observed over the next 48 hours. In contrast to its central effects, we found that oral DuP 753 (10 or 30 mg/kg) in normal spontaneously hypertensive rats resulted in sustained mean arterial pressure decreases of up to -74 mm Hg. These data suggest that, although the pressor effect of brain angiotensin II is mediated by the AT1 receptor, blockade of these receptors does not lower blood pressure in spontaneously hypertensive rats. In the spontaneously hypertensive rat, DuP 753 depresses blood pressure by blockade of peripheral, not central, AT1 receptors. PMID- 1592466 TI - Adenosine activates a vascular renin-angiotensin system in hypertensive subjects. AB - In vitro data indicate that the activation of A2 adenosine receptors increases renin release by the accumulation of cyclic AMP. Because in human forearm vessels beta-adrenergic receptor stimulation causes the local release of renin and angiotensin II through the increase of cyclic AMP, we evaluated in six essential hypertensive subjects whether adenosine can release vascular angiotensin II. Adenosine was infused into the brachial artery at cumulatively increasing doses (0.5, 1.5, and 5 micrograms/100 ml forearm tissue per minute for 5 minutes each) during saline infusion and in the presence of the adenosine antagonist theophylline (100 micrograms/100 ml forearm tissue per minute for 15 minutes), while venous (ipsilateral deep forearm vein) and arterial (brachial artery) angiotensin II (picograms per milliliter) were measured at the end of each infusion period, and forearm angiotensin II net balance (picograms per minute) was calculated by venous-arterial differences corrected for forearm blood flow (strain-gauge venous plethysmography) and hematocrit. In control conditions, adenosine, at higher doses, caused a dose-dependent vasodilation and increased venous angiotensin II without affecting arterial values; therefore, the calculated angiotensin II net balance showed an adenosine-mediated dose-dependent release. Theophylline pretreatment blunted adenosine-mediated forearm blood flow increments and angiotensin II release. The local origin of angiotensin II was further confirmed in another group of six hypertensive subjects in whom the angiotensin converting enzyme inhibitor captopril, locally infused at the rate of 2.5 micrograms/100 ml forearm tissue per minute for 15 minutes, abolished the adenosine-mediated venous angiotensin II increments. Our data indicate that exogenous adenosine can stimulate the production of angiotensin II in the forearm vessels of hypertensive patients. PMID- 1592467 TI - Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats. AB - Endothelin-1 (ET-1), a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, has been previously shown to produce a sustained, salt sensitive elevation in mean arterial pressure when chronically infused over a 7 day period into male Sprague-Dawley rats. In addition to other physiological actions, ET-1 has been shown to have potent effects on various renal functions, including renin production. Activation of the renin-angiotensin system, therefore, may contribute to the pressor response induced by ET-1. In this investigation, captopril ([2S]-1-[3-mercapto-2-methylpropionyl]-L-proline), a sulfhydryl-containing angiotensin I converting enzyme inhibitor, was chronically administered to endothelin-infused rats to elucidate the role of the renin angiotensin system in this animal model of hypertension. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6.0 meq.day-1 sodium intake throughout the experiment, with daily measurements taken of mean arterial pressure, heart rate, water intake, urine output, and urinary sodium and potassium excretions. Infusion of ET-1 alone at a rate of 5.0 pmol.kg-1.min-1 for 7 days was associated with a significant and sustained increase in mean arterial pressure; concomitant chronic administration of captopril in another group of rats at a rate of 1.0 mg.kg-1.hr-1 prevented the ET-1-induced hypertension. In an additional study, however, increases in plasma angiotensin II concentration were not observed in rats administered ET-1 alone at 5.0 pmol.kg-1.min-1. These results indicate that endothelin-induced hypertension may involve stimulation of the renin-angiotensin system but not an increase in circulating angiotensin II concentration. PMID- 1592468 TI - Role of tissue renin in the pathophysiology of hypertension in TGR(mREN2)27 rats. AB - A transgenic rat line, TGR(mREN2)27, was established by introducing the murine Ren-2 gene into the genome of rats by microinjection techniques. These rats exhibit severe hypertension, making them an interesting model in which to study the role of renin in the pathophysiology of hypertension. However, although the additional renin gene is the only genetic difference compared with control rats, the exact mechanism of hypertension in TGR(mREN2)27 rats is still unclear. It cannot be attributed to a stimulation of the endocrine renin-angiotensin system or to an overexpression of renin in the kidney, since plasma and kidney renin and renin gene expression in the kidney are low in these animals. Here we describe recent progress made toward elucidating mechanisms of hypertension in TGR(mREN2)27 rats. 1) TGR(mREN2)27 rats were bred to homozygosity. The development of high blood pressure in homozygous rats is accelerated compared with that of heterozygous rats. This is paralleled by a higher mortality rate in homozygous TGR(mREN2)27 rats. Blood pressure and mortality rate of homozygous transgenic rats were effectively reduced by 10 mg captopril per kilogram body weight. 2) Treatment of 8-week-old heterozygous TGR(mREN2)27 rats with 10 mg/kg body wt per day of the angiotensin II receptor antagonist DuP 753 for 4.5 weeks normalized blood pressure. After withdrawal of the drug, blood pressure increased rapidly, reaching control levels after 3 weeks. In another group of TGR(mREN2)27 rats treated with 0.5 mg/kg per day, there was no change in blood pressure. Plasma renin and plasma angiotensin II were significantly higher in the high-dose group compared with the low-dose group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592469 TI - Increased vascular angiotensin formation in female rats harboring the mouse Ren-2 gene. AB - Rats harboring the mouse Ren-2 transgene develop hypertension despite low levels of plasma renin activity. We tested the hypothesis that these rats exhibit an increase in vascular angiotensin formation caused by the presence of the transgene. We measured the release of angiotensins I and II from isolated perfused hindquarters by high-performance liquid chromatography and radioimmunoassay. Female rats heterozygous for the transgene had significantly elevated mean arterial pressure compared with control rats (189.3 +/- 9.5 versus 110.0 +/- 5.4 mm Hg, p less than 0.05). Plasma angiotensin II was significantly decreased in transgenic rats. Transgenic rat hindquarters released more angiotensin I (121 +/- 37 versus 39 +/- 12 fmol/30 min, n = 7 each) and more angiotensin II (210 +/- 21 versus 62 +/- 12 fmol/30 min, p less than 0.05, n = 7 each) than control rat hindquarters. Captopril increased angiotensin I release and decreased angiotensin II values in both transgenic and control rat hindquarters. Bilateral nephrectomy 24 hours before hindquarter perfusion greatly reduced angiotensin release from control rat hindquarters but not from transgenic rat hind limbs. We also tested for the presence of Ren-2 messenger RNA in mesenteric and aortic tissue by RNase protection assay and Northern blot analysis. We found that Ren-2 messenger RNA was present in mesenteric and aortic tissue of transgenic but not of control rats. We conclude that the Ren-2 transgene is expressed in vascular tissue of transgenic rats and may be responsible for substantial increases in vascular angiotensin formation. PMID- 1592470 TI - Polymerase chain reaction analysis of renin in rat aortic smooth muscle. AB - Controversy exists whether vascular smooth muscle cells in vivo synthesize renin, thereby providing a critical component of the hypothesized vascular renin angiotensin system. To examine this question, we enzymatically isolated and pooled the medial layer of thoracic aortas from Sprague-Dawley rats that were either untreated or enalapril treated for 3 days, isolated messenger RNA (mRNA), and performed Northern blot analysis with rat complementary DNA (cDNA) probes for renin, cathepsin D, and cathepsin E. Renin mRNA was detected in kidney but was not detected in aortic smooth muscle from the untreated or enalapril-treated groups. Cathepsin E mRNA was detected in enalapril-treated aorta and kidney, and cathepsin D mRNA was detected in all tissues examined. cDNA was synthesized and subjected to polymerase chain reaction analysis by using primers corresponding in sequence to regions conserved throughout the aspartic proteinases. Cathepsins D and E were amplified from kidney and aortic cDNA. Renin was less consistently amplified from the aortic cDNA and was much less abundant than cathepsin E or cathepsin D. These results suggest that 1) renin mRNA is present in aortic smooth muscle cells in vivo in quantities detectable only after multiple rounds of polymerase chain reaction amplification, 2) renin mRNA is not upregulated in aortic smooth muscle after converting enzyme inhibition, and 3) cathepsins D and E are the predominant aspartic proteinases in aortic smooth muscle. PMID- 1592471 TI - Local renin-angiotensin system in human adrenals and aldosteronomas. AB - The local renin-angiotensin system may regulate adrenal cell growth and function. Angiotensinogen, renin, and angiotensin converting enzyme gene expression were studied in four normal adrenal glands (removed from patients with renal carcinomas) and five aldosterone-secreting adenomas. Northern blot analysis showed expression of angiotensinogen messenger RNA (mRNA) in normal adrenals at levels approximately 35-fold lower than liver and sixfold lower than kidney. Similar angiotensinogen mRNA levels were present in two aldosteronomas, whereas a third had levels approximately 50% of those found in kidney. Renin mRNA was detectable in most normal adrenals and in three adenomas, one of which had relatively high renin mRNA levels. Angiotensin converting enzyme gene was expressed in adrenal tissue and in three adenomas. Portions from these normal adrenals and two of these aldosteronomas, as well as samples from two other adrenals and three aldosteronomas, were also studied in an in vitro superfusion system coupled with active renin radioimmunometric assay, angiotensin II/III, and aldosterone radioimmunoassay. Total amounts of active renin and angiotensin II/III released from normal adrenals during 270 minutes of superfusion were higher than the amounts released from aldosteronomas (312 +/- 35 versus 187 +/- 43 and 823 +/- 100 versus 436 +/- 55 pg/100 mg tissue, respectively; mean +/- SEM, p less than 0.05), whereas aldosterone release from the adenomatous tissue was approximately threefold higher (320 +/- 21 versus 115 +/- 18 ng/100 mg tissue; mean +/- SEM, p less than 0.01). Total amounts of active renin and angiotensin II/III released by normal or adenomatous adrenal samples exceeded threefold to fourfold the amounts extracted from similar samples of the same surgical specimen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592472 TI - Cardiovascular determinants of carotid artery disease. The Rotterdam Elderly Study. AB - The objective of the present study was to assess the prevalence of moderate and severe stenosis of the right carotid artery in the elderly and its associations with smoking, blood pressure, serum lipid levels, and hemostatic factors. The Rotterdam Elderly Study is a recently started single-center prospective follow-up study of a cohort of 11,854 elderly people aged 55 years or more. In 1990, 954 participants of the Rotterdam Elderly Study underwent ultrasonic duplex examination of the right internal carotid artery. A reduction of the lumen diameter of 16-49% was found in 29 people (3.0%). Severe stenosis (50% or more) was observed in 13 people (1.4%). With differences in age, sex, and body mass index taken into account, subjects with moderate-to-severe carotid artery disease had, compared with participants without stenosis, lower mean high density lipoprotein cholesterol levels (mean difference, 0.10 mmol/l; 95% confidence interval, 0, 0.20) and higher mean fibrinogen levels (difference, 0.24 g/l; 0.04, 0.45). Among them were more people with hypertension (mean difference, 16%) and more current smokers (mean difference, 13%). Factor VIIc and factor VIIIc activity was higher in subjects with carotid artery disease, without, however, reaching statistical significance (mean difference, 0.06 IU/ml [-0.01, 0.12] and 0.21 IU/ml [-0.05, 0.47], respectively). Our data suggest that hypertension, smoking, and reduced serum high density lipoprotein cholesterol levels, combined with unfavorable increases in hemostatic factors, may be related to carotid artery disease in the elderly. PMID- 1592473 TI - Rat adrenal cortex is a source of a circulating ouabainlike compound. AB - To determine if the adrenal gland may be the source of plasma-borne ouabainlike compound (OLC) in rats, we 1) measured immunoreactivity expressed as OLC equivalents in extracts from a wide variety of central and peripheral tissues and, for adrenal cortex and medulla, chromatographed the extracts to determine to what extent immunoreactivity in the adrenal was OLC, and 2) measured OLC in the plasma of adrenalectomized and adrenal demedullectomized rats. The highest levels of immunoreactivity were found in adrenal cortex, adrenal medulla, atria, and the pituitary. Based on high-performance liquid chromatographic retention time, immunoreactivity in the adrenal cortex was almost exclusively immunoreactive OLC. Removal of this rich source of OLC from rats resulted in an approximate 50% decrease in circulating levels of OLC by 6 days after removal. Furthermore, although adrenal demedullectomy also caused a decrease in OLC 3 days after surgery, the decline was sustained only with total adrenalectomy, in that plasma levels of OLC in demedullectomized rats 6 days after surgery had returned to levels equal to those of sham controls. Taken together, these findings strongly suggest that the adrenal cortex is a major contributor to circulating OLC in the rat. PMID- 1592474 TI - Pressure-induced activation of membrane K+ current in rat saphenous artery. AB - Pressurization of isolated arteries may result in Ca(2+)-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K+ channels is augmented by rises in cytosolic Ca2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K+ channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca(2+)-free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K+ channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16 +/- 1 mV) than at 25 mm Hg (10 +/- 1 mV). The sensitivity of K+ current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K+ current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6 fold by the Ca2+ ionophore A23187 (10 microM), suggesting a Ca2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K+ channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction. PMID- 1592475 TI - Signal transduction pathways in constriction of the basilar artery in vivo. AB - We examined effects of a putative myosin light chain kinase inhibitor in the cerebral circulation in vivo. In anesthetized rats, diameter of basilar arteries was measured through a cranial window (control, 232 +/- 10 microns, mean +/- SEM). Vessel diameter was measured during topical application of agonists and antagonists. ML-7, which has been reported to compete with adenosine triphosphate for binding to the catalytic site on myosin light chain kinase, attenuated vasoconstriction in response to prostaglandin F2 alpha (10(-6) M; -22 +/- 1% before versus -14 +/- 1% and -3 +/- 2% during ML-7, 10(-7) and 10(-6) M, respectively; p less than 0.05). ML-7 (10(-6) M) did not affect baseline diameter. Responses to serotonin (10(-8) M) and phorbol 12,13-dibutyrate (10(-8) M) were not attenuated by ML-7. Thus, constriction of the basilar artery induced by prostaglandin F2 alpha in vivo is attenuated by an inhibitor of myosin light chain kinase. PMID- 1592476 TI - High potassium diets greatly increase growth-inhibiting agents in aortas of hypertensive rats. AB - High potassium diets greatly reduce intimal and medial thickening in stroke-prone spontaneously hypertensive rats (SHRSP). In vascular smooth muscle cells, transforming growth factor-beta (TGF-beta) inhibits proliferation. To test whether high potassium diets decrease aortic thickening through TGF-beta, we measured TGF-beta-like activity in medium bathing aortas from rats fed either normal potassium or high potassium diets. Five-week-old SHRSP were fed 6% high NaCl diets containing either normal (0.5%) potassium (11 rats) or high (2.1%) potassium (14 rats) for 7 weeks. Aortas were freshly excised and perfused for 3 hours with tissue culture medium at ordinary arterial pressures. TGF-beta-like activity in the acid-activated perfusing medium was assessed using the growth inhibitory action on mink lung cells. Growth inhibition was assessed by [3H]thymidine incorporation. In the medium perfusing the outside of the aorta, the growth inhibitory rates were 2.5 times higher in high potassium SHRSP than in normal potassium SHRSP (-49% versus -20%, p less than 0.03). Antibodies to TGF beta 1 and TGF-beta 2 were added to other aliquots and did not alter the results whatsoever. Thus, the difference in growth inhibition was not due to differences in TGF-beta. The high potassium aortas released 2.5 times more growth-inhibiting agents than the normal potassium aortas. The same pattern of growth inhibition was also seen using vascular smooth muscle cells rather than mink lung cells (r = +0.818, p less than 0.001, n = 13). The increased growth inhibition of high potassium aortas was not due to an increased release of heparin.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592477 TI - Induction of endothelin-1 gene by angiotensin and vasopressin in endothelial cells. AB - To elucidate the cellular mechanism of endothelin-1 biosynthesis induced by angiotensin and vasopressin, we first cloned and sequenced full-length bovine preproendothelin-1 complementary DNA (cDNA) from a cultured bovine carotid artery endothelial cell cDNA library. The predicted bovine preproendothelin-1 consists of 202 amino acid residues and has a high percentage of homology to human, porcine, and rat preproendothelin-1 (70%, 81%, and 77%, respectively). Big endothelin-1, an intermediate form, consists of 39 residues differing only at position Val28 from porcine (Ile28) and His27 from rat (Arg27). The predicted 21 residue mature endothelin-1 is identical to human, porcine, rat, canine, and mouse endothelin-1. Northern blot analysis with the cloned cDNA as a probe demonstrated that a single 2.3-kb preproendothelin-1 messenger RNA (mRNA) is expressed not only in endothelial cells, but also in various bovine tissues, including lung, brain, heart, intestine, kidney, ovary, and urinary bladder. Angiotensin II and arginine vasopressin immediately and dose-dependently induced expression of preproendothelin-1 mRNA, whose effects were abolished by specific receptor antagonists. These findings suggest that stimulation of endothelin-1 secretion from endothelial cells by both agonists may be principally due to induction of preproendothelin-1 mRNA. PMID- 1592478 TI - Role of nitric oxide in renal papillary blood flow and sodium excretion. AB - Renal medullary interstitial infusion of NG-nitro-L-arginine (120 micrograms/hr, n = 7) decreased papillary blood flow to 71 +/- 5% of control without altering outer cortical flow. Before NG-nitro-L-arginine infusion, interstitial acetylcholine administration (200 micrograms/hr) increased cortical and papillary blood flow to 134 +/- 6% and 113 +/- 2% of control, respectively. After NG-nitro L-arginine administration, the vasodilator response to acetylcholine was abolished. In clearance experiments, renal medullary infusion of NG-nitro-L arginine (120 micrograms/hr, n = 7) significantly decreased total renal blood flow by 10%, renal interstitial fluid pressure by 23%, sodium excretion by 34%, and urine flow by 39% without altering glomerular filtration rate, fractional sodium and water excretion, blood pressure, or urine osmolality. These data indicate that selective inhibition of nitric oxide in the renal medullary vasculature reduces papillary blood flow, which is associated with decreased sodium and water excretion. We conclude that nitric oxide exerts a tonic influence on the renal medullary circulation. PMID- 1592479 TI - Nitric oxide modulates vascular tone in preglomerular arterioles. AB - Blockade of nitric oxide reduces renal blood flow, but the site or sites at which nitric oxide alters renal vascular resistance are unknown. The effects of N omega nitro-L-arginine (100 microM), an inhibitor of nitric oxide synthesis, on the pressure-diameter relation of renal arterioles was studied using a rat juxtamedullary microvascular preparation perfused in vitro with a physiological salt solution containing 5% albumin. The basal diameters of the main arcuate and interlobular arteries and the proximal and distal afferent arterioles averaged 438 +/- 26, 64 +/- 4, 30 +/- 1, and 20 +/- 1 microns, respectively, at a perfusion pressure of 80 mm Hg. The diameters of the arcuate and interlobular arteries increased by 14 +/- 2% and 7 +/- 2%, whereas the proximal and distal afferent arterioles decreased by 3 +/- 1% and 7 +/- 2% when perfusion pressure was elevated to 160 mm Hg. Nitro-arginine had no effect on the basal diameters of arcuate and interlobular arteries. Nitro-arginine reduced the diameters of afferent arterioles by 7 +/- 2% at all perfusion pressures studied. Nitro arginine increased active vascular tone in the interlobular artery and afferent arterioles and enhanced autoregulation of glomerular capillary pressure. L Arginine (1 mM), the precursor to nitric oxide production, reversed the effects of nitro-arginine. These findings suggest that nitric oxide modulates vascular tone of the interlobular artery and afferent arterioles of deep nephrons and influences the ability of the preglomerular vasculature to autoregulate glomerular capillary pressure. PMID- 1592480 TI - Role of nitric oxide in mediating renal response to volume expansion. AB - The objective of the present study was to determine the role of endothelium derived nitric oxide in mediating the renal response to extracellular volume expansion with isotonic saline (5% body weight). In anesthetized dogs (n = 7) and before volume expansion, nitric oxide synthesis was inhibited in the right kidney by continuous intrarenal infusion of NG-nitro-L-arginine-methyl ester (1 microgram/kg/min). Arterial pressure and renal hemodynamics of both kidneys did not change significantly either during nitric oxide synthesis inhibition or during 5% volume expansion. However, in response to extracellular volume expansion, increases in natriuresis, diuresis, and fractional excretion of lithium (an index of proximal sodium reabsorption) were inhibited in the right kidney by 27%, 28%, and 41%, respectively, when compared with the contralateral kidney. Increases of renal interstitial hydrostatic pressure during 5% volume expansion were not statistically different between both kidneys. In another group of dogs (n = 4), the administration of L-arginine (0.5 mg/kg/min) into the right renal artery prevented the renal effects induced by the nitric oxide synthesis inhibitor during volume expansion. The findings in this study suggest that nitric oxide production plays an important role in regulating the renal response to extracellular volume expansion. The proximal tubule seems to be involved in the reduced renal excretory response to volume expansion during nitric oxide synthesis inhibition. PMID- 1592481 TI - Attenuated afferent arteriolar response to acetylcholine in Goldblatt hypertension. AB - We tested the hypothesis that endothelium-dependent afferent arteriolar vasodilation is impaired in the nonclipped kidney of two-kidney, one clip Goldblatt hypertensive rats relative to sham-operated controls. Five to six weeks after positioning of a 0.25-mm clip on the left renal artery, systolic pressure averaged 173 +/- 10 mm Hg in Goldblatt rats and 118 +/- 4 mm Hg in controls (p less than 0.01). The right kidney was harvested for videometric study of the microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from Goldblatt and control rats were perfused at renal arterial pressures of 150 and 110 mm Hg, respectively. Afferent arteriolar inside diameter did not differ between control (20.3 +/- 0.7 microns) and Goldblatt (21.1 +/- 1.7 microns) kidneys. Determination of afferent responses to increasing concentrations of the endothelium-dependent vasodilator acetylcholine (1 nM to 10 microM) in the bathing solution unveiled a shift to the right in the dose response relation in Goldblatt rats. Afferent arterioles from control kidneys dilated significantly when exposed to 1 nM acetylcholine, whereas a 1,000-fold higher concentration was required to dilate arterioles from Goldblatt rats. Sodium nitroprusside, an endothelium-independent vasodilator, increased afferent diameter to a similar extent in both groups. In a separate group of normal kidneys, vasodilator responses to 10 microM acetylcholine were completely blocked by 1,000 microM nitro-L-arginine, an inhibitor of nitric oxide synthesis. Thus, endothelium-dependent afferent vasodilation appears to be impaired in the nonclipped kidney of Goldblatt hypertensive rats. This phenomenon could contribute to the altered renal hemodynamic status characteristic of Goldblatt hypertension. PMID- 1592483 TI - Prostaglandin H2 and thromboxane A2 are contractile factors in intrarenal arteries of spontaneously hypertensive rats. AB - Vascular resistance is increased in the kidneys of spontaneously hypertensive rats (SHR). Previous studies have demonstrated impaired vascular relaxations of mesenteric resistance arteries of SHR because of increased production of a cyclooxygenase-dependent endothelium-derived contracting factor. To test the hypothesis that altered endothelial function contributes to the enhanced constriction in kidneys of SHR, endothelium-mediated relaxations of renal resistance arteries from 5-6-week-old prehypertensive SHR and Wistar-Kyoto rats were compared in arteriographs. Acetylcholine induced endothelium-dependent contractions in SHR arteries, while potent endothelium-dependent relaxations were noted in renal arteries from Wistar-Kyoto rats. Inhibition of cyclooxygenase (indomethacin) or blockade of prostaglandin H2-thromboxane A2 receptors (SQ 29,548) blocked acetylcholine-induced contractions in SHR renal arteries; relaxations in SHR renal arteries after either treatment were similar to those observed in renal arteries from Wistar-Kyoto rats. NG-Nitro-L-arginine inhibited acetylcholine-mediated relaxations in both SHR and Wistar-Kyoto arteries. Endothelium-independent relaxations induced by verapamil were comparable in SHR and Wistar-Kyoto arteries. Thus, the impaired response to acetylcholine in SHR renal resistance arteries may result from the release of endothelium-derived cyclooxygenase products (prostaglandin H2 or thromboxane A2), which oppose endothelium-derived nitric oxide-mediated relaxation. PMID- 1592482 TI - Angiotensin II and renal functional reserve in rats with Goldblatt hypertension. AB - We have previously demonstrated that loss of renal functional reserve (renal response to protein loading) in two-kidney, one clip Goldblatt hypertension is characterized by no change in glomerular filtration rate or single nephron glomerular filtration rate and decreased absolute proximal tubular reabsorption during glycine administration. Captopril restores proximal reabsorption and renal functional reserve in this condition. Because captopril suppresses angiotensin II generation and increases bradykinin, prostaglandins, and potentially nitric oxide, we have investigated the role of angiotensin II blockade in restoring proximal reabsorption and renal functional reserve by comparing captopril with DuP 753, an angiotensin II receptor antagonist, in Goldblatt rats. One month after clipping, two period micropuncture studies (control and glycine) were performed on the unclipped kidney. Normal rats and three groups of clipped rats were studied: an untreated group (HYP), a group treated with captopril (CEI), and a group treated with DuP 753 (DuP) 5 days before micropuncture. Glycine increased glomerular filtration rate, nephron plasma flow, and single nephron glomerular filtration rate in normal rats. Systemic and glomerular hypertension in HYP rats was associated with loss of renal functional reserve and a decrease in absolute proximal reabsorption during glycine. Captopril and DuP 753 normalized systemic and glomerular capillary pressure and prevented the decrease in proximal reabsorption during glycine; however, only CEI rats increased single nephron glomerular filtration rate and glomerular filtration rate after glycine. In conclusion, abnormal responses of both glomerular and tubular function are responsible for the loss of renal functional reserve in Goldblatt rats. Inhibitory angiotensin II activity is responsible for decreasing proximal reabsorption during glycine; however, factors other than angiotensin II limit the glomerular response to glycine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592484 TI - Effect of intrarenal bradykinin infusion on vasopressin release in rabbits. AB - Electrical stimulation of afferent renal nerves and activation of renal mechanoreceptors increase plasma vasopressin concentrations. In the present study, the effect of renal chemoreceptor activation on plasma vasopressin concentration was investigated in anesthetized rabbits. Renal chemoreceptors were activated with intrarenal infusions of bradykinin. With intrarenal infusion of bradykinin at 136 ng/min, plasma vasopressin concentration increased from 4.5 +/- 1.5 to 26.8 +/- 14.2 pg/ml at 5 minutes (p less than 0.01), whereas with infusion at 1,360 ng/min, plasma vasopressin increased from 5.9 +/- 2.0 to 54.4 +/- 16.4 pg/ml at 5 minutes (p less than 0.01). There was no significant change in plasma vasopressin during intravenous infusion of bradykinin at 136 ng/min. Infusion at 1,360 ng/min increased plasma vasopressin from 2.7 +/- 0.5 to 14.8 +/- 6.4 pg/ml (p less than 0.01), but this increase was significantly less than that produced by intrarenal infusion of the same dose of bradykinin. Similar effects on plasma vasopressin were observed during paired intrarenal and intravenous infusions of bradykinin at 136 ng/min. Renal denervation markedly reduced the vasopressin responses to intrarenal infusion of bradykinin at 136 ng/min (2.8 +/- 0.5 to 4.0 +/- 0.7 pg/ml, p less than 0.01) and 1,360 ng/min (3.2 +/- 0.7 to 7.8 +/- 1.8 pg/ml, p less than 0.05). These results indicate that bradykinin stimulates vasopressin release by an intrarenal action and suggest that this action is mediated by afferent renal nerves. PMID- 1592486 TI - Second Bristol-Myers Squibb Lifetime Achievement Award in Hypertension. 1991. PMID- 1592487 TI - Eighth annual Marion Merrell Dow Hypertension Research Clinical Fellowship Award. 1991. PMID- 1592485 TI - Interferon gamma attenuates hypertensive renal injury in salt-sensitive Dahl rats. AB - Evidence has been provided that the immunological mechanism is involved in the genesis or maintenance of hypertension. In the present study, we investigated the effects of interferon gamma, a potent immunomodulator derived from lymphocytes, on hypertension and organ damage in Dahl salt-sensitive rats and in spontaneously hypertensive rats. Subcutaneous injection of interferon gamma (5 x 10(4) units/kg body wt once a week for 10 weeks) reduced blood pressure in Dahl salt-sensitive rats fed a 4% high salt diet (174 versus 194 mm Hg, p less than 0.025). This blood pressure reduction was associated with an improvement of renal functions, an increase in glomerular filtration rate (690 versus 569 ml/day/100 g body wt, p less than 0.05), and decreases in urinary protein excretion (48 versus 78 mg/day/100 g body wt, p less than 0.025) and urinary N-acetyl-beta-D glucosaminidase excretion (143 versus 183 milliunits/day/100 g body wt, p less than 0.05). Morphological investigation showed a marked resolution of the vascular injuries seen in untreated Dahl salt-sensitive rats, e.g., intimal and medial hyperplasia, with infiltration of inflammatory cells, and significant amelioration of the glomerular sclerotic changes. In contrast, interferon gamma affected neither blood pressure nor renal functions in spontaneously hypertensive rats. These data indicate that interferon gamma ameliorates the development of hypertension and vascular and renal injuries in Dahl salt-sensitive rats. The resolution of vascular and renal injuries contributes, in part, to the antihypertensive action of interferon gamma. PMID- 1592488 TI - Effect of prostaglandin E1 on leukotriene C4-induced increases in vascular permeability of hamster cheek pouch. AB - Our goal was to determine whether there is a synergistic effect of prostaglandin E1 (PGE1) on leukotriene C4 (LTC4)-induced increases in vascular permeability of the hamster cheek pouch in vivo. Changes in permeability were quantified by counting venular leaky sites (LS) and calculating clearance (CLR) of fluorescein isothiocyanate (FITC)-dextran 70kDa, during suffusion of the cheek pouch with LTC4 in the absence or presence of PGE1. LTC4 produced a dose-related increase in LS and CLR, and PGE1 (0.01 microM) significantly potentiated the effect of LTC4. During suffusion with LTC4 (15.0 nM) in the absence of PGE1, LS increased from 0 to 19 +/- 3/0.11 cm2 and CLR increased from 0.3 +/- 0.1 to 1.0 +/- 0.2 x 10(-6) ml/sec. During superfusion with LTC4 (15.0 nM) in the presence of PGE1, LS increased from 0 to 40 +/- 3/0.11 cm2, and CLR increased from 0.4 +/- 0.1 to 2.1 +/- 0.5 x 10(-6) ml/sec. To determine whether the effect of PGE1 on LTC4-induced increases in vascular permeability was related to the vasodilatory effect of PGE1, we examined the effect of isoproterenol (ISO). In contrast to that observed with PGE1, ISO decreased LTC4-induced increases in LS and CLR. Our data suggest that there is a synergistic effect of PGE1 on LTC4-induced increases in venular permeability that is not mediated by a vasodilatory action of PGE1. PMID- 1592489 TI - Mechanisms of endothelial cell-dependent leukocyte adhesion stimulated by platelet-activating factor. AB - Platelet-activating factor (PAF) stimulates leukocyte-endothelial cell (EC) adhesion through its effects either on leukocytes or on ECs. ECs may be injured, synthesize, or express new adhesive proteins to increase leukocyte adhesion. Intermediary mediators produced by activated ECs are also likely involved in promoting leukocyte adhesion. Our experiments demonstrated that PAF induced no obvious damage to bovine pulmonary artery ECs evaluated by lactic dehydrogenase release rate, angiotensin-converting enzyme activity, and cellular malondialdehyde content. Treatment of EC monolayers with 10(-9) M PAF increased polymorphonuclear leukocyte (PMN) adhesion. Increasing PAF concentration did not induce more PMN adherence. PAF elicited both a rapid and prolonged increment of PMN adherence to EC monolayers. The rapid adherence was greatly attenuated by pretreatment of ECs with PAF receptor antagonist SRI 63-441 but was not affected by pretreatment of PMNs with SRI 63-441, suggesting that PAF increases PMN adherence rapidly through its effects on specific receptors on ECs. Increased PMN adherence lasted if PAF treatment of ECs was sustained for 3 or 6 h. Pretreatment of ECs with actinomycin D, a protein synthesis inhibitor, significantly decreased PAF-induced sustained PMN adherence, but the inhibition is incomplete, suggesting that other mechanisms than protein synthesis also participated in the prolonged PMN adherence. We concluded from the results that PAF may induce both rapid and prolonged PMN adhesion to ECs. The effects are receptor mediated. The prolonged PMN adhesion is partly the result of protein synthesis. PMID- 1592490 TI - Induction of neutrophil infiltration by rat chemotactic cytokine (CINC) and its inhibition by dexamethasone in rats. AB - In vivo effects of cytokine-induced neutrophil chemotactic factor (CINC) derived from rats on neutrophil infiltration were investigated using an air-pouch-type inflammation model in rats, and effects of dexamethasone on neutrophil infiltration induced by CINC was also examined in order to gain further insight into the mechanism of antiinflammatory activity of glucocorticoids. Injection of CINC into the air pouch made on the dorsum of rats induced a marked infiltration of neutrophils into the pouch fluid but not mononuclear cells and eosinophils during a 30-min interval after the injection. Maximum effect was induced at a dose of 1.4 micrograms/pouch. Treatment with dexamethasone 3 h before the injection of CINC suppressed the neutrophil infiltration in a dose-dependent manner, but no complete inhibition was observed. CINC injection into the air pouch of rats that had been sacrificed by bleeding in order to minimize neutrophil infiltration from blood stream also stimulated neutrophil infiltration into the pouch fluid when the carcass was incubated at 37 degrees C for 30 min, but the number of infiltrated neutrophils was about 35% of CINC-induced neutrophil infiltration in intact rats. CINC-induced neutrophil infiltration in the carcass, which is supposed to be a reflection of neutrophil migration from extravascular space in subcutaneous tissues to pouch fluid, was not inhibited by dexamethasone treatment. Therefore, the inhibition of neutrophil infiltration by dexamethasone might be due to inhibition of the extravasation of peripheral neutrophils but not due to inhibition of neutrophil chemotaxis from subcutaneous extravascular space to pouch fluid. These findings suggest that clinical effects of steroidal antiinflammatory drugs on neutrophil infiltration in inflammatory disease is partly due to inhibition of neutrophil extravasation induced by preformed neutrophil chemotactic factors in the inflammatory site. PMID- 1592491 TI - Phagocytosis by lipopolysaccharide-primed human neutrophils is associated with increased extracellular release of reactive oxygen metabolites. AB - The effect of priming human neutrophils with lipopolysaccharide was investigated regarding the respiratory burst activity generated during phagocytosis of IgG- or C3b-opsonized yeast particles. LPS pretreatment significantly enhanced the respiratory burst activity, measured as luminol-amplified chemiluminescence, of both types of opsonized particles. In control cells most of the activity was produced intracellularly, probably in the phagosomes. In the primed cells, however, extracellular release of reactive oxygen metabolites was significantly increased during Fc- and CR3-mediated phagocytosis (P less than 0.01 and P less than 0.002, respectively). The release was most pronounced when using C3b opsonized particles. Potent oxygen metabolites acting together with lysosomal enzymes are of importance in inflammatory-induced tissue damage. An increased extracellular release of reactive oxygen species by phagocytizing primed neutrophils can therefore lead to greater damage to the surrounding tissues. PMID- 1592492 TI - Comparison of sequence of cDNA clone with other genomic and cDNA sequences for human C-reactive protein. AB - A clone for C-reactive protein (CRP) has been isolated from a human liver cDNA library; this clone harbors a plasmid, pC81, which has an insert of 1631 bp. When compared to genomic and cDNA sequences published to date now, pC81 has revealed homologies and differences that might help to clarify the structure of this gene and the presence of allelic variants in man. PMID- 1592493 TI - Breast feeding revisited. PMID- 1592494 TI - Delayed contact and breast feeding. AB - Fifty two mother-infant pairs were studied. Of these, twenty six belonged to the normal vaginal delivery group where babies were roomed in with their mothers immediately after birth. Twenty six belonged to the cesarean group where the mother and baby were separated for 2.8 +/- 1.0 days. The social support was comparable in the two groups. No significant difference was found in the number of mothers breast feeding their infants at four weeks postpartum. PMID- 1592495 TI - Clinical and bacteriological study of normal and inflamed neonatal conjunctivae. AB - Maternal vaginal and neonatal conjunctival flora were prospectively studied in a 117 mother baby pairs. The commonest isolates from both vaginal and conjunctival flora were E. coli, Staphylococcus aureus and Klebsiella species. In 85% of mother-baby dyads, isolates from vagina and conjunctiva were similar. The commonest bacterial isolates in neonates with conjunctivitis were Staphylococcus aureus (37.4%), E. coli (27.9%) and Klebsiella species (19.3%). Maternal coitus, infections, rupture of membranes and baby's birth weight and sex did not influence the occurrence of conjunctivitis. PMID- 1592496 TI - Neonatal hypoglycemia--clinical profile and glucose requirements. AB - A total of 2248 infants born at All India Institute of Medical Sciences Hospital, New Delhi were selectively screened for hypoglycemia over a period of 15 months. Hypoglycemia (blood glucose less than 30 mg/dl) was diagnosed in 107 cases (4.8%). Preterm babies had three times increased risk (12.8%) as compared to term babies (3.6%). Small-for-dates (SFDs) and large-for-dates (LFDs) infants were at increased risk of manifesting hypoglycemia (7 and 10 times, respectively) as compared to the appropriate-for-dates (AFDs) babies (2.7%). Approximately two thirds of the hypoglycemic babies (67.3%) had one or more risk factors including birth asphyxia (24.2%), diabetic mothers (23.8%), respiratory distress (13.9%) and septicemia (11.6%). A total of 59.8% cases were asmyptomatic while the rest had one or more symptoms. The most common symptom observed was lethargy (81.4%), followed by jitteriness (67.4%), respiratory abnormalities (41.9%), hypotonia (39.5%) and seizures (30.2%). The amount of glucose (mg/kg/min) needed to maintain a stable blood sugar in various categories of hypoglycemic babies was observed to be in the following decreasing order of amount; symptomatic babies with seizures (Gp IV), IGDM's/IDM's and symptomatic babies with other features (Gp III), SFDs and LFDs (Gp II) and AFDs (Gp I). Such a categorization of hypoglycemic babies will help to treat them more precisely. PMID- 1592497 TI - Computerised neonatal case records: a four year experience. AB - A computerized system for neonatal case records has been used for the last four years at Kasturba Hospital. The software was developed in-house. The data base can be used to generate discharge summaries, neonatal statistics and epidemiological information. For a single patient, entry of data and printing of the discharge summary takes four to five minutes. Consolidated demographic and epidemiological statistics or selective clinical data for clinical research is easily retrievable. The system is efficient, accurate and easy to operate. PMID- 1592498 TI - Adverse drug reaction monitoring of ciprofloxacin in pediatric practice. AB - Ciprofloxacin, a fluoroquinolone antibacterial agent, is not recommended in pediatric population on account of its possible adverse effect on growing cartilage. It is being commonly used for treatment of variety of infections in children in our country and very little information is available on the risks involved in its use. A questionnaire was sent to 750 pediatricians in the last week of November 1990, to retrospectively judge over the previous 2 month period the extent of its use and identify the adverse drug reactions (ADRs). One hundred and fifty-four pediatricians replied, of which 147 had prescribed ciprofloxacin in a total of 3341 patients under 18 years of age, enteric fever being the commonest indication for its use. One hundred and fifty-nine ADRs were reported in 104 (3.1%) patients. They were: gastrointestinal in 50% of these 104 patients, CNS in 23%, skin and allergic in 19.1%, musculoskeletal in 8.6%, hematological in 3.8%, CVS in 2.9% and nephrological in 0.9% cases. Of 159 ADRs, 8 (5%) were severe, 76 (47.8%) were moderate and 75 (47.2%) were mild. Therapy needed discontinuation in only 9 (0.3%) patients. Two new ADRs were identified, viz., sudden death after intravenous ciprofloxacin and sinus nodal arrest causing bradycardia. PMID- 1592499 TI - Rural neonatal care: Dahanu experience. AB - The Rural Neonatal Care Project, started by the Government of Maharashtra in the Ganjad Primary Health Centre, Dahanu block in Maharashtra, had the TBA as the sheet anchor for delivery of neonatal care. Maintenance of "warm chain" and resuscitation of an asphyxiated baby were recognized as the most important interventions besides detection of a very low birth weight/preterm baby and safe transportation of such a baby. Foot length measurement from foot print was used as a surrogate to birth weight as an indicator for referral. Neonatal and perinatal mortality rates dropped appreciably over 3 years and the antenatal registration went up by 30%. The cost of this programme is affordable and the programme itself was acceptable to the community and the TBAs because of its simplicity. PMID- 1592500 TI - Occupational morbidity among children employed in brassware industry. AB - Fifty seven male children between ages of 10-16 years engaged in the brassware industry at Moradabad in Northern India were studied for occupational morbidity. The finding were compared with those obtained in the children (n = 29) engaged in other ancillary units which did not involve exposure to the metal fumes and dust in their work environment. The study showed a high prevalence of respiratory morbidity in the children engaged in the main units in comparison to those employed in the ancillary units (40.3 vs 27.6%; p less than 0.05). This was associated with significantly higher prevalence of pulmonary impairment in the former group (21.0%) particularly demonstrating restrictive ventilatory abnormality (10.5%) followed by bronchial obstruction (7.0%). The high respiratory morbidity may be attributed to chronic exposure to the fumes and dust of the metals such as nickel, chromium and cadmium. The children employed in the ancillary as well as in the main units showed high prevalences of musculo skeletal disorders (27.6 and 22.8%) which may be caused by sustained faulty posture adopted during work and physical stress. PMID- 1592501 TI - Nutritional requirements in infancy. PMID- 1592502 TI - Breast feeding and weaning practices among urban Muslims of district Lucknow. PMID- 1592503 TI - Supplementary feeding pattern in children living in a resettlement colony. PMID- 1592504 TI - Breast feeding practices amongst mothers having undergone cesarean section. PMID- 1592505 TI - Vitamin D requirements of children in Haryana. PMID- 1592506 TI - Screening of rickets in a Haryana town. PMID- 1592507 TI - Platelet function tests in protein energy malnutrition. PMID- 1592509 TI - Kostmann syndrome. PMID- 1592508 TI - Gastric teratoma in children. PMID- 1592510 TI - Salmonella senftenberg carrier state in a neonate following septicemia. PMID- 1592511 TI - Persistent pulmonary hypertension in the newborn. PMID- 1592512 TI - Poliomyelitis and immunization status. PMID- 1592513 TI - Charter for care of children in hospital. PMID- 1592514 TI - Computer programmes in pediatrics. PMID- 1592515 TI - Intraosseous infusion. PMID- 1592516 TI - Quality improvement: the gurus and their approaches. PMID- 1592517 TI - How to critically evaluate an anesthesia practice: lessons from the American Society of Anesthesiologists. PMID- 1592518 TI - Case review process using a systems approach. PMID- 1592519 TI - Continuous quality improvement in an anesthesia residency training program. PMID- 1592520 TI - Implementing continuous quality improvement: a private practice's experience. AB - The "golden rules" of CQI, from our experience, could be summarized as follows: 1. Create the appropriate environment first by teaching the Deming principles. 2. Establish effective methods of group communication. 3. Do not focus on individual error. Focus on processes and your system of care. Make certain that case presentations do not spotlight individuals. 4. Look for the common causes of problems. 5. Use statistical methods appropriately. Identify what is clinically important. Make any data collection effort meaningful, and make sure that all members understand why the data is being collected. 6. If an error is identified, ensure that the practitioners involved are active participants in the analysis. 7. Recognize good performance. If something is done well, have the provider present the case to the group. This step is particularly worthwhile if the case illustrates a new process that will remedy a problem other members of the department have experienced. PMID- 1592521 TI - The influence and activities of government on quality of care. PMID- 1592522 TI - The anesthesia database, the automated record, and the quality assurance process. PMID- 1592523 TI - Quality assurance/peer review for recredentialing/relicensure in New York State. AB - In consultation with the State Health Department, the New York State Society of Anesthesiologists has developed a Model Program of Quality Assurance/Peer Review for Recredentialing/Relicensure. The Model Program was developed to provide a standardized peer review process through which anesthesiologists practicing in New York State can be recredentialed and relicensed when recredentialing becomes a requirement for relicensure of New York State physicians. The program of recredentialing and relicensure is part of the agenda of the Governor's office, the State Health Department, and the State Education Department to improve the quality of healthcare in New York State through (1) identifying physicians whose quality of care is below reasonable thresholds, (2) assuring that these physicians receive appropriate remedial education or training, and (3) generally raising the quality of healthcare provided by all physicians practicing in New York State. PMID- 1592524 TI - Report on the third Japanese-German Workshop on Molecular and Cellular Aspects of Carcinogenesis. Meeting held at Essen, Germany, October 24-26, 1991. PMID- 1592525 TI - Levels of expression of breast epithelial mucin detected by monoclonal antibody BrE-3 in breast-cancer prognosis. AB - Taking into consideration the relationship of breast neoplasia with recent knowledge obtained on the molecular structure and biosynthesis of the breast epithelial mucin, an epitope on this molecule detected by monoclonal antibody (MAb) BrE-3 was chosen as a marker to study the correlation of expression of the mucin and prognosis in infiltrating ductal carcinomas of the breast. Strong statistical validation was obtained in the use of BrE-3 in immunohistochemical procedures where scores for the expression of the mucin on paraffin-embedded sections of the primary breast tumors were studied. Four different immunohistochemical variables measuring levels of expression (intensity or prevalence) in cytoplasm or membrane were obtained for each of 227 patients' breast tumors and subjected to Kaplan-Meier univariate and Cox proportional hazards multi-variate analysis. Additionally, traditional prognostic variables for breast-cancer prognosis (grade of differentiation, age, tumor size, axillary lymph-node involvement and estrogen receptors) were subjected to identical analyses. In uni-variate analysis, low cytoplasmic intensity, high membrane prevalence, and high membrane intensity of mucin expression were each found to be significantly associated with good prognosis in relation to both survival or relapse time. In multi-variate analysis, all 4 immunohistochemical parameters were significantly associated with both survival and relapse time in these patients. Among the traditional variables, 3 (axillary-node involvement, grade of differentiation and tumor size) were also found to be statistically significant at the uni-variate and multi-variate level. A multi-variate analysis of the combined immunohistochemical and traditional variables identified the 4 immunohistochemical parameters, tumor size and axillary-node involvement as having the highest level of association with either survival or relapse time. These variables were then combined and served to define a prognostic model [ILCPS(Comb)], which was found to have the capacity to separate the patient population studied into 4 prognostic groups in terms of survival and 3 groups in terms of relapse. As expected, the ILCPS(Comb) was shown to have a higher level of prognostic association with both survival and relapse than the individual variables themselves, the traditional variables together or the immunohistochemical variables together. Our approach develops a theoretical framework and a statistical model, employing levels of expression of the breast epithelial mucin and 3 traditional variables, which identifies, in terms of prognosis, distinct sub-populations of patients with infiltrating breast carcinoma with defined risk functions. PMID- 1592526 TI - No influence of beta-carotene on smoking-induced DNA damage as reflected by sister chromatid exchanges. AB - The putative cancer-preventive potential of beta-carotene may be explained by its anti-oxidant capacity to prevent free-radical-induced DNA damage. To evaluate this hypothesis, we studied the effect of 14 weeks of beta-carotene supplementation on the frequency of sister chromatid exchanges (SCE) in lymphocytes in 143 heavy smokers in a randomized, double-blind, placebo controlled intervention trial. Age, smoking habits and pretreatment blood levels of cotinine, beta-carotene, retinol and vitamins C and E were similar in the placebo group (n = 73) and the treatment group (n = 70). Plasma beta-carotene levels increased 13-fold in the treatment group during intervention, whereas the other parameters remained stable in both groups. Initial SCE levels were similar in the treatment and placebo groups (5.10 +/- 0.98 vs. 5.00 +/- 0.99 SCE/lymphocyte). During the intervention, both groups showed an almost identical decrease, and at the end of the intervention period there was no difference in SCE levels between the treatment and the placebo groups (4.37 +/- 0.38 vs. 4.24 +/- 0.37 SCE/lymphocyte). This study shows no protective effect of beta-carotene on DNA damage as reflected by sister chromatid exchanges in lymphocytes. Our results thus do not yield support for a cancer-preventive mechanism of beta carotene involving this form of DNA damage. It cannot be excluded, however, that beta-carotene prevents other forms of smoking-induced DNA damage, affects other tissues, or is preventive in later stages of carcinogenesis. PMID- 1592527 TI - Pharmacodynamics and pharmacokinetics of intravesical mitomycin C upon different dwelling times. AB - The schedule in dosing of intravesical chemotherapy has thus far received little attention. Correlation of optimal contact time with bladder toxicity, as well as maximal chemotherapeutic effect for one of the drugs of first choice for intravesical instillation, i.e. mitomycin C (MMC), is a particularly important question. In a randomized study, we treated bladder cancer patients with intravesical MMC using 30-min and 60-min dwelling times. There were 28 evaluable patients in each of the 2 groups. The groups were comparable with respect to mean age, sex ratio and distribution of primary or recurrent and single or multiple tumors. Stages and grades of tumors were also comparable over both treatment groups. Pharmacokinetics of MMC and degradation/metabolism were monitored during the first 4 cycles and the last (8th) cycle using HPLC and mass spectrometry. Recurrence was significantly lower in the 60-min treatment group (35.7% vs. 14.3%, chi 2 test; 0.01 less than p less than 0.05). No recurrences were found in patients with Ta and T1 tumors when the 60-min dwelling time was used. Toxicity was mild and transient; the incidence was, surprisingly, lower in the 60-min group but the difference failed to reach the level of significance. Pharmacokinetics of systemic MMC and recovery in the urine was comparable over both groups and systemic absorption was calculated to be in the range of 1-5%. PMID- 1592528 TI - Loss of HLA class-I alleles, heavy chains and beta 2-microglobulin in colorectal cancer. AB - Using immunohistochemical methods, we have analysed colorectal biopsies of normal mucosa, metaplastic polyps (5 cases), adenomas (15 cases) and adenocarcinomas (70 cases) with 13 monoclonal antibodies (MAbs) to allelic products of the HLA-A, B, C loci. Nine of the 70 carcinomas showed total loss of HLA Class-I molecules due to an underlying defect regarding not only the expression of beta 2-microglobulin (beta 2-m), but also the heavy chains of HLA A, B and C loci, or both. Much commoner was a loss of one or more Class-I alleles as follows: A1/Aw36 (completely lost in 4 of 29 cases and focally lost in another 2), A2 (in 1 of 37 cases), A3 (in 2 of 14 cases), A1 1/28/31/33 (in 3 of 11 cases), B7 (in 3 of 13 and focally in 1 other case), B17 (in 1 case), Bw4 (in 8 of 45 and focally in another 6), Bw6 (in 9 of 62 and focally in another 3). Focal selective loss (Bw6 and a combined A1-Bw6), was observed in 2 adenomas. Normal colonic mucosa, as well as stromal and lymphoid cells present between the neoplastic glands, were studied in each case as a control. A particular allele was only considered to be lost by the malignant cells if it was still expressed on these adjacent tissues. PMID- 1592529 TI - High protein, saturated fat and cholesterol diet, and low levels of serum lipids in colorectal cancer. AB - In a case-control study probing the role of diet on the occurrence of colorectal cancer and undertaken in Athens, Greece, sera were collected from 100 cases and 100 controls, and serum total cholesterol, high-density-lipoprotein (HDL) cholesterol and triglycerides were determined. The biochemical results were analyzed in conjunction with nutrient intakes and a dietary score that summarizes in a linear way the dietary contrast between high-risk (high protein, saturated fat and dietary cholesterol; low vegetable) and low-risk (low protein, saturated fat and cholesterol; high vegetable) patterns. Cases with colorectal cancer had significantly (p less than 0.001) and substantially lower values of serum total cholesterol and particularly HDL cholesterol, but these associations did not reflect dietary practices, since protein intake and, to a lesser (and nonsignificant) extent, saturated fat and dietary cholesterol intake were higher among cases than among controls. In absolute terms, the dietary effect (as summarized in the linear dietary score) is more evident among persons with low serum total cholesterol and HDL cholesterol than among those with high levels of these serum lipids. These results indicate that a diet beneficial with respect to the risk of coronary heart disease is also likely to reduce the risk of colorectal cancer, even though low levels of serum total cholesterol and particularly HDL cholesterol represent important independent correlates of clinically overt colorectal cancer. PMID- 1592530 TI - Risk of lung cancer among cigarette and pipe smokers in southern China. AB - Studies in Shanghai and in north-east China indicate that cigarette smoking is a major contributor to the high rates of lung cancer in those areas, but doubts persist regarding the influence of cigarette use on lung cancer rates in other areas of China. In addition, the risk of lung cancer associated with other methods of tobacco consumption--in particular, the use of bamboo water-pipes and long-stem pipes--is uncertain. A population-based case-control study of 427 male lung cancer patients residing in a mining area of Southern China and 1,011 controls was carried out to address this and other issues. Of these patients, 63% smoked cigarettes and (water and long-stem) pipes; 17% and 14% smoked only cigarettes or pipes, respectively; and 6% did not smoke. Compared to non-smokers, smokers of cigarettes only, smokers of pipes only and mixed smokers were at increased risk; OR = 2.6 (95% CI 1.1-6.2), 1.8 (95% CI 0.8-4.2) and 4.1 (95% CI 2.3-9.2), respectively. Risk increased with duration of tobacco use; however, the rate of increase with years of cigarette use was significantly greater than for years of pipe use (p = 0.03). In addition, risks increased 8-fold in the highest quartile of number of cigarettes per day compared to non-cigarette smokers vs. 2.3-fold for the highest quartile of number of liang (50 g) smoked per month compared to non-pipe-smokers; the trends in the ORs differed significantly (p less than 0.001). Results suggest that, in this area of China, tobacco use is an important cause of lung cancer, and that smoking cigarettes may be more deleterious than smoking pipes (primarily water pipes). PMID- 1592531 TI - Independent clinical, histological and quantitative prognostic factors in transitional-cell bladder tumours, with special reference to mitotic frequency. AB - A cohort of 537 transitional-cell bladder cancers (TCC) was followed up for a mean of 9 years. Clinical stage, WHO grade, papillary status, 6 nuclear factors and volume-corrected mitotic index (M/V index) were related to progression and survival. Classic and quantitative prognostic factors were significantly interrelated (p less than 0.001). In Ta-Tl tumours M/V index predicted progression independently (p less than 0.001) and in the entire cohort progression was related independently to the M/V index (p = 0.0001) and to the WHO grade (p = 0.0022). In survival analysis, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001), papillary status (p less than 0.0001) and nuclear factors (p less than 0.0001) were significant predictors. In papillary tumours, clinical stage (p less than 0.0001), M/V index (p less than 0.0001), WHO grade (p less than 0.0001) and nuclear factors (p = 0.0001-0.0133) were related to survival. In a multivariate analysis T-category (p less than 0.001), WHO grade (p less than 0.001), M/V index (p = 0.002) and papillary status (p = 0.034) predicted survival independently in the entire cohort whereas in papillary tumours T-category (p less than 0.001) and M/V index (p less than 0.001) were independent predictors. If tumours with pelvic lymph-node metastases or distant metastases at diagnosis were excluded from the analysis, T-category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p less than 0.001) were independent predictors. In papillary tumours T category (p less than 0.001), M/V index (p less than 0.001) and WHO grade (p = 0.048) predicted survival. The results emphasize the importance of mitotic activity as a most important histological prognostic factor in TCC, second only to clinical stage. In Ta-TI tumours quantitative mitotic frequency analysis includes all the available independent prognostic information. Accordingly, TCC can be graded by mitotic frequency analysis in place of subjective grading systems. PMID- 1592532 TI - Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis. AB - The inhibitory effect of oral administration of betel-leaf extract (BLE) and 2 of its constituents, beta-carotene and alpha-tocopherol, as single agents or in combination with dietary turmeric on methyl(acetoxymethyl)nitrosamine (DMN-OAC) induced oral carcinogenesis in Syrian hamsters was studied. DMN-OAC was administered twice monthly for 6 months. The chemopreventive effect of BLE or its constituents with turmeric was determined by comparing tumor incidence observed in treated groups with that seen in control animals. The apparent site-specific chemopreventive effect of BLE or its constituents was demonstrated by inhibition of tumor incidence, reduction of tumor burden, extension of the tumor latency period and regression of established, frank tumors. The inhibitory effect of BLE or its constituents combined with turmeric was higher than that of the individual constituents. The study suggests that BLE could be developed as a potential chemopreventive agent for human oral cancer. PMID- 1592533 TI - Hydrolyzable tannins: potent inhibitors of hydroperoxide production and tumor promotion in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate in vivo. AB - The anti-oxidant and the anti-tumor-promotion activities of several hydrolyzable tannins (HTs), including a commercial tannic-acid (TA) mixture, were examined in mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) in vivo. A single application of TPA gradually increases the hydroperoxide (HPx)-producing activity of the epidermis, which is maximally stimulated at 3 days and returns to control levels at 9 days. Pre-treatments with TA and ellagic acid (EA) strongly inhibit, in a dose-dependent manner, this HPx response to TPA. Total inhibition by TA lasts for about 16 hr, beyond which it is substantially reduced but not completely lost. TA can also reduce the level of epidermal HPx when it is applied 36 hr after the tumor promoter. EA is an antioxidant 10 times more potent than TA and n-propyl gallate (PG), which are equally effective against TPA-induced HPx production. Gallic acid is the least effective of the HTs in inhibiting HPx formation. TA also inhibits the production of HPx induced by several structurally different tumor promoters and the greater HPx responses produced by repeated TPA treatments. When applied 20 min before each promotion treatment, twice a week for 45 weeks, several HTs inhibit the incidence and yield of papillomas and carcinomas promoted by TPA in initiated skin. Overall, TA is more effective than EA and PG in inhibiting skin-tumor promotion by TPA, suggesting that the anti oxidant effects of HTs are essential but not sufficient for their anti-tumor promotion activity. PMID- 1592534 TI - Pleiotropic actions of suramin on the proliferation of human breast-cancer cells in vitro. AB - Suramin, a non-specific growth factor antagonist, is currently under investigation for treatment of cancer patients. We studied its action on 6 different human breast-cancer cell lines in vitro. In complete growth medium, pleiotropic effects were observed with respect to cell proliferation, i.e. suramin is stimulatory at low concentrations and inhibitory at higher concentrations, for 4 of the 6 cell lines studied. The various cell lines showed marked differences with respect to the antiproliferative action of suramin, the Evsa-T cells being by far the most sensitive ones. A suramin concentration of 100 micrograms/ml brought about a 100% stimulation of the proliferation of ZR/HERc cells, ZR 75.1 cells ectopically expressing a human epidermal growth factor receptor (EGF-R) cDNA. Although less pronounced (10 to 60% stimulation), a similar response was observed for the parent ZR 75.1 cells, as well as for T-47D and MDA-MB-231 cells. The non-specificity of the action of suramin was established by the observation that suramin-induced inhibition of cell proliferation could be abolished by insulin-like growth factor-I (IGF-I) or basic fibroblast growth factor (bFGF), and even by estradiol, both in complete growth medium and under defined serum-free conditions. Our data indicate that suramin exerts pleiotropic effects on the proliferation of human breast cancer cells in vitro, and confirm the non-specific nature of its action. The stimulatory effect of low concentrations of suramin on the proliferation of breast cancer cells may have important consequences for breast cancer patients treated with suramin. PMID- 1592535 TI - A monoclonal anti-idiotypic antibody bearing the image of an epitope specific to the human carcinoembryonic antigen. AB - One concept for immune therapy of patients bearing carcinomas involves monoclonal anti-idiotypic antibodies (Malds) to trigger the immune system of the host into a response against the tumor cells. Current theory states that so-called internal image Malds bearing epitopes specific to a given tumor-associated antigen would be most suited for that purpose. We report here the generation of syngeneic Malds generated against the murine monoclonal immunoglobulin T84.66 (Ab1), which defines a single epitope on the protein moiety of the carcinoembryonic antigen (CEA). This antigenic determinant is unique to CEA, as it is absent in other members of the CEA gene family that are expressed in a variety of normal human tissues, including granulocytes. The Mald 6G6.C4 (Ab2) exhibits the immunochemical features of an internal image antibody mimicking the epitope recognized by the idiotype T84.66. In enzyme immunoassays the binding of Ab1 to Ab2 is completely inhibited by CEA. In addition, Mald 6G6.C4 only binds to native but not to the denatured or reduced idiotype. Immunization of rabbits with F(ab')2-fragments of 6G6.C4 results in antisera (Ab3) that show specificity to CEA in both binding and inhibition enzyme immunoassays as well as in Western blots. Finally, Ab3 did not detect NCA, a major CEA-related glycoprotein in Western blots, either in a purified form or in a crude tumor extract, indicating a high specificity of the anti-anti-idiotypic response. In summary, these immunochemical data show that the monoclonal anti-idiotype 6G6.C4 can functionally mimic a CEA-specific epitope in rabbits and may do so in humans. Therefore, this antibody may have a clinical potential as a network antigen for active immune therapy in patients suffering from CEA-positive carcinomas. PMID- 1592536 TI - Treatment of L1210 murine leukemia with liposome-incorporated N4-hexadecyl-1-beta D-arabinofuranosyl cytosine. AB - N4-alkyl-1-beta-D-arabinofuranosyl cytosines as lipophilic derivatives of the widely used anti-tumor drug 1-beta-D-arabinofuranosylcytosine (ara-C) were synthesized and incorporated into unilamellar liposomes. The resulting preparations yielded stable unilamellar liposomes with diameters ranging between 40 and 70 nm. The liposomal derivatives exhibited an increased anti-tumor effect against the murine L1210 lymphoid leukemia at optimal molar concentrations which were 16 times lower than those previously reported for free ara-C. The N4-alkyl ara-C derivatives with alkyl chains containing 14-16 C-atoms were highly effective against L1210 leukemia whereas shorter chains showed no cytostatic effects. The increased resistance to hydrolysis of the N4-alkyl-ara-C derivatives and the improved anti-tumor effect of the liposomal N4-hexadecyl-ara-C preparation compared to other known N4-acyl-ara-C prodrugs, together with the possibility of preparing large volumes of stable and sterile liposomes, hold out the prospect of more effective chemotherapy for leukemias. PMID- 1592537 TI - The presence of a concomitant bulky tumor can decrease the uptake and therapeutic efficacy of radiolabeled antibodies in small tumors. AB - We describe the effects that a concomitant large tumor mass can exert on the therapeutic efficacy of radioimmunotherapy against small tumors, using the nude mouse/GW-39 human colonic cancer model. The tumor uptake 7 days p.i. of i.v. injected 131I-labeled anti-CEA MAb (NP-4) and anti-CSAp MAb (Mu-9) in small (less than 0.2 g) s.c. GW-39 tumors was approximately 3-fold lower in animals with a concomitant large (greater than 1.0 g) GW-39 tumor than in the absence of a large tumor. An inverse correlation between the mass of the tumor burden and the 131I levels in the blood was observed, indicating that a large tumor mass may act as a sink for the injected radiolabeled antibody. Increasing antibody protein dose did not reverse the reduced uptake in the small s.c. tumors. The therapeutic efficacy of a single 0.25-mCi injection of 131I-labeled anti-CSAp MAb Mu-9 towards intrapulmonary GW-39 metastases was tested in nude mice bearing either small or large GW-39 s.c. tumors. Over 80% of the animals with small s.c. GW-39 tumors survived 18 weeks after tumor transplantation, whereas less than 20% of the animals bearing large s.c. tumors survived past 13 weeks. Dosimetric calculations, based on biodistribution data over time, indicated that the presence of a large s.c. tumor mass may have decreased the radiation dose to the intrapulmonary tumors almost two-fold. However, the radiation dose to the blood was also decreased in the animals with the large tumor burden. Therefore, the animals with larger tumor burden may also have been able to sustain higher doses of the radioantibody. The presence of a large tumor mass can thus affect the biodistribution and therapeutic efficacy of radioiodinated antibodies. We suggest that bulky tumors can adsorb a considerable amount of the injected dose, thereby reducing the total amount of MAb available for binding to the smaller tumors. PMID- 1592538 TI - SOD2: a new type of tumor-suppressor gene? AB - The activity of superoxide dismutases (SOD) 1 and 2 was analysed in correlation with mRNA and chromosome content in 6 SV40-transformed (TF) and in non transformed (NF) human fibroblast cell lines. Total SOD activity was fairly constant, whereas the ratio SOD2/SOD1 was much lower in TF than in NF. The decrease in SOD2 activity was correlated with a low mRNA content, and with the presence of various chromosomal rearrangements leading to deletions of the long arm of chromosome 6 where the gene is mapped. In contrast, chromosome 21, carrying the gene for SOD1, was not found to be deficient and the SOD1 activity was high. This shows that in TF, the activity of SOD2 is largely determined by gene dosage. It has been proposed that SOD activity could be inversely correlated with cell proliferation, and that SOD2 activity, in particular, was related to cell differentiation. Thus, there is a cascade of events occurring in cell transformation, involving gene deregulation, chromosome (gene) deletion, low mRNA and protein content, low enzyme activity, and acquisition of growth advantage which makes the SOD2 gene a possible new type of tumor-suppressor gene. PMID- 1592539 TI - Comparative anti-viral and anti-proliferative activity of PGA1 and PGJ2 against HTLV-I-infected MT-2 cells. AB - Prostaglandin (PG) A and J exert anti-viral and anti-proliferative effects in a number of experimental models. In particular, multiple treatments with PGAs prevent in vitro the clonal selection of HTLV-I-infected and potentially transformed cord-blood-derived mononuclear cells. Proliferation of HTLV-I infected leukemic T cells is refractory in most cases to conventional anti blastic therapy. We examined whether these cyclopentenone PGs might control cell proliferation and/or alter virus replication also in HTLV-I-transformed cells. We show that PGA1 and PGJ2 can exert powerful control of proliferation of the HTLV-I immortalized, virus-producing MT-2 cell line, in a concentration-dependent fashion. Cells were preferentially arrested at the G1/S interface by treatment with PGA1 or PGJ2 without any detectable cellular toxicity. The anti proliferative effect of PG treatment was independent of the growth phase of MT-2 cells, since both asynchronous and synchronous cells were sensitive to treatment. This effect was accompanied by an increase in the synthesis of a 70 kDa heat shock protein (HSP70). However, synthesis of HSP70 was induced to a much greater extent by PGJ2 than by PGA1 at the same concentration. Neither PGA1 or PGJ2 inhibited the transcription of HTLV-I in MT-2 cells, but treatment with PGJ2, and not with PGA1, moderately inhibited the synthesis of viral proteins, i.e., p40 Tax and p19 core proteins. Moreover, infection of recipient K562 cells was significantly inhibited after pre-treatment of MT-2 cells with PGJ2 14 hr before or co-treatment at the onset of the co-culture with K562 cells. This effect was not obtained when MT-2 cells were repeatedly pre-treated with PGJ2 for 1 week before co-culturing. This suggests that reduced infection could be related to impairment of some step in virus-transmission phase. PMID- 1592540 TI - High in vitro-in vivo correlation of drug response using sponge-gel-supported three-dimensional histoculture and the MTT end point. AB - The in vitro sponge-gel-supported three-dimensional histoculture chemosensitivity assay (Hoffman assay) allows the in vivo-like culture of human tumors. In this study, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H tetrazolium bromide (MTT) end point was applied to the Hoffman assay in an attempt to increase in vitro-in vivo correlation. The chemosensitivities of 16 human tumor lines were determined in vitro by the histoculture assay, and retrospectively correlated to their in vivo chemosensitivity as xenografts in nude mice. The in vitro test was considered to be positive if tumor-cell MTT reduction activity was lowered by more than 50%. The cutoff drug concentrations to determine sensitivity in vitro were determined for mitomycin C, doxorubicin, 5-fluorouracil and cisplatin. Using these cutoff drug concentrations in vitro we found, as a function of time of exposure, a strong correlation between serum drug concentrations found in nude mice given maximum tolerated doses and drug concentrations found in the histoculture media in vitro, thereby establishing a relationship between the amounts of drugs to which tumors were exposed in vivo and in vitro. The overall correlation rate of the efficacy results of the drug-response assay to in vivo chemosensitivities was 89.8%, with 90.0% true-positive and 89.7% true-negative rates, 81.7% sensitivity and 94.6% specificity, thereby indicating potential clinical use for tumor histoculture with the MTT end point. PMID- 1592541 TI - Effect of theophylline in chronic obstructive lung disease. AB - The bronchodilator, respiratory center and respiratory muscle effects of oral sustained release theophylline are investigated with a placebo controlled double blind study in 34 patients with chronic obstructive lung disease (COLD). The first 3 days were a theophylline washout period and the patients did not receive theophylline and on the 4th day, serum theophylline concentration was negligible. Initial pulmonary function tests were performed. Twenty-four of the patients took 350 mg oral sustained release theophylline twice a day. Ten of the patients were given placebo. On day 7, serum theophylline concentrations of the study group were in therapeutic doses and the tests were repeated. Bronchodilator effect was assessed by spirometry, flow-volume loops and measuring airway resistance (Raw). Respiratory muscle function was assessed by measuring maximal inspiratory (PImax) and expiratory pressures (PEmax) and the effect on respiratory center was evaluated by minute ventilation, mouth occlusion pressure index and inspiratory duty ratio. Forced vital capacity in one second (p less than 0.001), maximal mid expiratory flow rate (p less than 0.05), maximal expiratory flow at 50 percent of vital capacity (p less than 0.001), maximal inspiratory pressure (p less than 0.01) increased, while airway resistance (p less than 0.05) decreased significantly. Mouth occlusion pressure and minute ventilation mouth occlusion pressure index did not change after theophylline therapy. In placebo group, there was no significant change in airway obstruction assessed by spirometry and flow volume loops or in respiratory muscle function assessed by maximal respiratory pressures. It is therefore, concluded that oral sustained release theophylline has a bronchodilator effect in irreversible chronic obstructive lung disease, increases respiratory muscle function, but in therapeutic doses has no effect on respiratory center. PMID- 1592542 TI - Comparison of absorption rates in bioequivalence studies of immediate release drug formulations. AB - For immediate release drug formulations, the maximum concentration (Cmax), the time to the maximum concentration (tmax), the mean residence time (MRT), and recently, the Cmax/AUC ratio have been suggested as absorption rate characteristics. Several authors have used simulation studies to investigate the relative merits of these characteristics. In contrast, we investigate here the "true" relationships between these four characteristics in a more theoretical manner. Specifically, we show that in the one-compartment open model the difference in tmax, and the ratio of the Cmax/AUC ratio of two drug formulations are equivalent characteristics for the comparison of the absorption rate of two drug formulations. In two- or higher compartment models these relationships hold approximately. This provides a powerful argument for the use of the observed Cmax/AUC ratio, rather than tmax, as a measure for the rate of absorption, because it is well-known that Cmax/AUC can be observed with higher precision than tmax. We also show that the difference in MRT for two-drug formulations equals the difference in mean absorption time under very general conditions, and for the one- and the two-compartmental model we prove this explicitly. Thus the difference in MRT emerges as the most direct characteristic of the difference in absorption rates, and in that sense is superior to both the tmax difference and the Cmax/AUC ratio. Based on empirical evidence and the results of simulation studies published in the literature we recommend that for drugs with short elimination half-lives, the difference in MRT is the primary characteristic for the comparison of absorption rates.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592543 TI - Pharmaceutical and biopharmaceutical quality of a sustained release carbamazepine preparation: a contribution to quality assurance. AB - Side effects observed during treatment with non-sustained release carbamazepine preparations are often due to the steep rise in plasma carbamazepine concentrations. To maintain plasma levels with only minor fluctuations between narrow limits, sustained release formulations have been developed which release the active constituent at a constant rate which is not too high. Bioavailability tests (single dosage, crossover design) and several investigations into the dissolution profile were carried out on three test batches of a sustained release carbamazepine preparation (Timonil 300 retard). The aim was a release model which, in the context of quality assurance, would not only facilitate reliable statements with regard to batch conformity, but would also be validated in respect of pharmacokinetic parameters such as rate of absorption and bioavailability. Correlations between mean dissolution times (MDT) and mean absorption times (MAT) at level B were found [Skelly et al. 1990]. A dissolution test differing from the pharmacopoeial tests was selected, which permitted the assessment of both batch conformity and biopharmaceutical batch quality. PMID- 1592544 TI - Toothpastes. AB - It is well known that plaque is the main cause of caries and parodontopathies, which puts the role of toothpastes as an important means of prevention of odontopathies to the foreground. Toothpastes can be more or less oriented towards having a particular effect, such as cleaning, anticaries effect, antimicrobial effect or inhibition of the formation of tartar. Toothpastes contain substances which promote dental health, such as abrasives (silicium dioxide, brushite, calcite, calcite and aragonite, gibbsite etc.), active components (fluorides, triclosan, metal ions, sanguinarine and surface-active substances), substances which motivate the use of toothpaste (sweetening agents, aromatic oil, colours) and components which are necessary for technical reasons, such as moisturizing agents, binders and opacifiers. PMID- 1592545 TI - Response to head-up tilt in cramping and noncramping hemodialysis patients. AB - Hemodialysis-associated skeletal muscle cramps are generally ascribed to a reduction in plasma volume, but during this procedure, it is not known how volume contraction results in cramps. To elucidate this mechanism, we compared responses to one hour of 60 degrees head-up tilt in 8 patients who cramped during no more than one-sixth of their dialyses and in 8 patients who cramped at least half the time. Age and recumbent blood pressure were similar in each group, but more patients with frequent cramps had diabetes underlying their renal failure (p = 0.013) and had been dialyzed for less than 3 years (p = 0.020). Baseline plasma renin activity and plasma norepinephrine and arginine vasopressin concentrations were similar in both groups, except plasma renin activity in one patient with frequent cramps, which was 15 times higher than in the other patients. After tilting, systolic blood pressure fell an average of 17% in patients who cramped infrequently (p = 0.0031) but only 10% in frequently cramping patients. The ratio of tilt/recumbent norepinephrine levels exceeded 1.5 in 7 patients with frequent cramps but was less than this in 6 patients who cramped infrequently (p = 0.020). One of the 2 infrequently cramping patients with a ratio above 1.5 was the only individual to have a normal renin response to tilt. We propose that cramps are prone to occur during hemodialysis in patients whose sympathetic nervous system response to volume stress is partially intact but is not modulated by concurrent activation of the renin-angiotensin system. PMID- 1592546 TI - Types of bioequivalence and related statistical considerations. AB - Approval of a generic alternative to an existing formulation carries the implication that the two formulations are "equivalent". However, there are many notions of equivalent. Current practice in bioequivalence studies defines equivalence solely in terms of average (or median) measures of bioavailability. Current methods for this average bioequivalence approach are commonly based on the two one-sided tests principle. Average bioequivalence is the special case of population bioequivalence, where the entire distribution of bioavailabilities is considered. Statistical approaches for population bioequivalence are suggested. Population bioequivalence is an improvement over average bioequivalence, because average bioequivalence does not consider the variabilities of the formulations. However, population bioequivalence is still not sufficient to ensure that an individual will respond similarly to the two formulations; that requires individual bioequivalence. Again, statistical approaches are suggested, one of which, a tolerance interval approach, appears to directly address the clinical question of switchability of formulations. We conclude that population bioequivalence is sufficient for marketing approval, but that individual bioequivalence is necessary for switchability. PMID- 1592547 TI - Recurrent otitis media with non-typable Haemophilus influenzae: the role of serum bactericidal antibody. AB - The effect of serum bactericidal antibody on colonization with non-typable Haemophilus influenzae (NTHI) was studied in 26 children. Serum bactericidal antibody did not prevent colonization with NTHI in the nasopharynx. Antibody was present in 53% before, 91% during and 100% after documented colonization of the nasopharynx with NTHI. In addition, 5 children with recurrent otitis media with effusion (OME) due to NTHI were observed for bactericidal serum antibody during a 4-year period. Bactericidal antibody against the causative NTHI strain was not detected in the acute sera of any patient during each episode, but was observed in the convalescent sera of all of the patients. The bactericidal antibody in the convalescent serum did not appear to be protective against colonization and recurrence of disease by a different heterologous strain of NTHI. However, bactericidal antibody was augmented in some cases by a heterologous infection with NTHI. We confirmed the emergence of new strains of NTHI with DNA fingerprinting and outer membrane protein (OMP) analysis. The data suggest that the immune response to NTHI in OME is usually strain-specific, and furthermore, the results demonstrate that strain-specific bactericidal antibody does not prevent colonization in the nasopharynx with the homologous or heterologous bacterial strains. In general, bactericidal antibody is not cross-protective against heterologous strains of NTHI causing a second or third episode of otitis media with NTHI. PMID- 1592548 TI - Effect of respiratory syncytial virus on adherence, colonization and immunity of non-typable Haemophilus influenzae: implications for otitis media. AB - Adherence of non-typable Haemophilus influenzae to respiratory epithelium was evaluated in a cotton rat model of respiratory syncytial virus (RSV) infection. Colonization with non-typable H. influenzae increased to a maximum within 4 days of RSV infection compared to RSV negative controls (4.58 +/- 0.17 vs 3.82 +/- 0.23 log colony forming units (CFU) per ml, P less than 0.05) and then declined over the subsequent 10 days (2.0 +/- 0 vs 3.78 +/- 0.39 CFU per ml, P less than 0.0001). In a second series of experiments, attachment of non-typable H. influenzae to epithelial cells collected from RSV infected cotton rats at the time of maximum virus replication was not different from controls (57.4 +/- 18.3 vs 52.0 +/- 24.3 bacteria per 50 cells). Systemic immunity to non-typable H. influenzae as measured by IgG-specific antibody to the outer membrane complex and bactericidal antibody did not influence colonization. These data suggest that colonization with non-typable H. influenzae is significantly affected by a concurrent infection with RSV; however, the site of bacterial attachment is not known. PMID- 1592549 TI - Occult and overt submucous cleft palate: from peroral examination to nasendoscopy and back again. AB - Peroral examination of the soft palate is of greater value than generally recognized. The nasendoscopic examination provides essential information on the velopharyngeal valve physiology and pathology. However, nasendoscopy cannot be performed in individuals who are uncooperative such as young children, patients with personality disturbances or those mentally retarded, or in the presence of severe deformity of the nose. In these patients the peroral examination is of particular practical clinical application. Forty cases of occult and overt submucous cleft palate were included in the present study. We describe the contribution of systematic assessment of the soft palate intraorally, based on a correlation with nasendoscopic examination of the velopharyngeal valve in speech. An accurate peroral examination can provide additional information on abnormality of the velar musculature as well as the existence of Passavant's ridge. This information is particularly important in children who are too young for nasendoscopix examination, but because of their poor speech intelligibility, early diagnosis and treatment are imperative. PMID- 1592550 TI - ENG findings of shunt-treated hydrocephalus in children. AB - Thirty-eight hydrocephalic children (mean age 11.5 years; range 5.1-17.9) were examined on average 7.9 years after initial shunting. The etiology of the hydrocephalus was divided into 5 groups: perinatal intraventricular hemorrhage 14, congenital obstructive hydrocephalus 14, central nervous system infections 4, intracranial cysts 3, and intracranial anomalies 3 children. Electronystagmographic (ENG) examination included recording of spontaneous and positional nystagmus, the pendular eye tracking test, saccadic eye movements, optokinetic and caloric reactions. Only 5 children (13%) had a normal ENG. Thirty one children (82%) had ENG pathology of the central type and 12 (44%) of the 27 successfully studied had pathological caloric reactions. Ten children (26%) had a combination of both central and vestibular pathology. There was no statistical difference between the boys and the girls or between different etiological groups. The high prevalence of vestibular pathology among these hydrocephalic children may be relevant to their impaired motor performance, because only 7 (18%) of the children studied exhibited normal motor performance in the neurological tests. PMID- 1592551 TI - Masseter spasm and malignant hyperthermia: a retrospective review of a hospital based pediatric otolaryngology practice. AB - It has been claimed that the combination of halothane and succinylcholine, commonly used for anesthetic induction during short pediatric otolaryngologic procedures, is associated with a 1% incidence of masseter spasm (MS) which may be an early sign of malignant hyperthermia (MH). An 18-month retrospective chart review of all patients undergoing general anesthesia at the Children's Hospital of Pittsburgh (n = 14, 112) was conducted to assess the incidence of MS and its management. In addition, a separate subgroup of patients identified as being at risk for MH was also evaluated. In the otolaryngology service, the incidence of developing MS was 2 of 206 (1%) in children who were anesthetized with halothane and received succinylcholine, patients were identified in the MH high-risk group, and none developed MH. The findings affirmed the risks of using this combination of anesthetic and neuromuscular blocking agents during induction and the need for establishing management guidelines. PMID- 1592552 TI - Experience with the audiologic assessment of infants and toddlers. AB - Experience with the behavioral assessment of hearing sensitivity is reported for 211 babies and toddlers aged 6-24 months. The visually reinforced head-turn procedure, visual reinforcement audiometry (VRA), was utilized to obtain threshold estimates for infants evaluated for both research and clinical purposes. At the initial test session, 90% of the infants and toddlers provided useful audiometric threshold data for air-conducted tonal signals; 84% could be assessed using standard earphones. The equipment arrangement described allows a single audiologist to complete the VRA assessment. The behavioral test technique offers the clinician a simple, efficient procedure for the routine audiometric assessment of the vast majority of very young children. PMID- 1592553 TI - An unusual case of Xanthoma disseminatum. AB - A 10-year-old boy was admitted to the University Hospital complaining of exhaustion, night sweats, coughing and dyspnea. Physical examination, laboratory findings and histopathological examination led to the diagnosis of Xanthoma disseminatum. Because of dyspnea a tracheostomy was performed 3 months before diagnosis was made. Outline of treatment and management of this patient is discussed in this paper. PMID- 1592554 TI - Hearing loss in Noonan syndrome. AB - A report is presented on a man of Turkish origin, with Noonan Syndrome and unilateral conductive hearing loss since early childhood. There was no history of otitis media. At the age of 23, exploratory tympanotomy revealed a total absence of the long process of the incus and a normal-looking tympanic membrane. The position of the normal-shaped mobile stapes was just medial, and not posteromedial, to the malleus. A congenital ossicular chain anomaly was diagnosed. An allograft malleus head was interposed between the stapes and the malleus. The resulting air-bone gap was less than 10 dB. A review of the literature is given on hearing loss in Noonan Syndrome. PMID- 1592555 TI - Mucoepidermoid carcinoma associated with acute lymphoblastic leukemia. AB - As treatment and survival of acute leukemia as well as other types of pediatric cancer improve, the number of second malignancies in these treated patients will increase. Occurrence of these second malignancies in the head and neck is not frequently reported although it is known that radiation treatment, chemotherapy and sometimes the primary lesion itself are risk factors for neoplasia. Malignancies of the parotid gland in the pediatric population are known to be unusual. We discuss a mucoepidermoid carcinoma in a 10-year-old female who 7 years earlier had undergone successful treatment of acute lymphoblastic leukemia. PMID- 1592556 TI - Middle ear disease in cleft palate children at three years of age. AB - Fourty-four cleft palate children consecutively referred to a plastic surgery unit were treated with palate repair at one year of age by one surgeon. The children were not routinely treated with ventilating tubes for middle ear disease. At 3 years of age they were investigated for aural pathology. Also specific antipneumococcal antibody activity was measured and was found to be compatible with the activity found in healthy age-matched control children. In the cleft palate children with no immaturity of the immune system only a slight increase in frequency of acute otitis media was evident. One third of the children had however suffered from long-standing secretory otitis media which can be regarded to be more common than what has been found in the normal population in several epidemiologic studies. At 3-4 years of age 82% of the children had a normal hearing indicating an improvement of the condition. PMID- 1592557 TI - Kawasaki disease: five-year experience at Children's National Medical Center. AB - Kawasaki Disease (KD) is an acute multisystem disease that predominately affects infants and children. Coronary artery aneurysms or ectasia may develop in 15-25% of children with the disease and may lead to myocardial infarction or sudden death. Head and neck manifestations are often the presenting symptoms, thus the otolaryngologist may be asked to evaluate a child early in the course of the disease. Otolaryngologist need to be familiar with the early symptoms of this disease so that prompt diagnosis may be made and appropriate therapy instituted. Recent therapeutic advances have been shown to be effective in reducing the prevalence of coronary artery abnormalities. The authors retrospectively reviewed cases of KD seen at Children's National Medical Center over a 5-year period. Sixty-nine cases were included in the reviews and all children exhibited head and neck manifestations upon admission. Our data and review of the relevant literature underscore the need for heightened awareness among our profession in regards to KD. PMID- 1592558 TI - Ectopic cartilage in subglottic stenosis: hamartoma or reaction to trauma? AB - In an experimental study in growing rabbits an endolaryngeal injury to the subglottis resulted in the development of a stenosis due to the formation of scar tissue containing ectopic cartilage. For comparison, biopsies taken from the subglottic stenosis in 8 children were studied histologically. In 6 cases ectopic cartilage was observed; all patients had a history of endotracheal intubation. In 3 children the diagnosis hamartoma was made. In the remaining 3 cases the formation of ectopic cartilage might have been a direct reaction to the endolaryngeal intubation. The observations suggest that the formation of ectopic cartilage in acquired subglottic stenosis is not always due to a developmental aberration such as a hamartoma. PMID- 1592559 TI - Modulation of humoral and cellular resistance in children with laryngeal papillomatosis. AB - As accessory cells in immunity response immunoglobulin and lymphocytes participate in antitumor immunity. Quantitative changes in concentrations and numbers were studied once before therapy, without examining the functional state. In order to gain more information on the humoral response during and after treatment, and in cases of recurrence, bactericidal antibodies against B. anthracis were determined by means of 51Cr-labeled microbes. The results of the present study show that IgG levels were normal and IgA and IgM normal or increased. In only 2 children (0.8%) the levels of serum IgM were lowered. Although a high percentage of increased trend values of bactericidity in cured children was found (75%), the percentage in children with recurrences reaching 50%, the differences are considered statistically insignificant. Following T lymphocyte, figures a significant decrease in juvenile laryngeal papillomatosis (JLP) patients were found. PMID- 1592560 TI - Pediatric tracheotomy referrals to speech-language pathology in a children's hospital. AB - The pattern of referral of infants and children with tracheotomy to speech language pathology (SLP) was studied through a retrospective review. Less than half (29/62) were referred to SLP with no difference by surgical service (otolaryngology vs pediatric surgery) or length of time with tracheotomy. Younger children were referred far less frequently than older children. Furthermore, more than half of all children referred to SLP showed moderate to severe communication deficits. Central nervous system abnormalities were documented in 66% of the subjects. In the majority tracheotomies were in place longer than 12 months. On the basis of the findings, a protocol was established for early routine involvement of SLP with infants and children with tracheotomy. PMID- 1592561 TI - Management of cystic hygroma of the head and neck in Lagos, Nigeria; a 10-year experience. AB - Management of cystic hygroma in 25 children as practised in Lagos, Nigeria during 1980 through 1989 was studied. Thirteen (52%) were infants out of which 7 were newborns. Thirty-three operations were performed including those for recurrences. There were 29 excisions out of which 22 (76%) were one-stage complete excisions. Complications included 4 cases of facial paresis, 6 recurrences and respiratory obstruction which led to death in 5 newborns, the only deaths in the series, and an operative mortality of 20.8%. A striking feature of this study is the observation that some recurrences occurred at sites which were normal at the initial or previous excision. Such recurrences led to 4 surgical operations at different times in one child. The term 'Progressive Infilterating cystic Hygroma' (PICH) is being suggested to distinguish this type from the ordinary cystic hygroma. PMID- 1592563 TI - Shoulder abnormalities in association with branchio-oto-renal dysplasia in a patient who also has familial joint laxity. AB - A patient with branchio-oto-renal dysplasia and associated shoulder abnormalities is presented. The combination of features makes discrimination from the oto facial-cervical syndrome difficult. Shoulder abnormalities should be regarded as a rare feature of the branchio-oto-renal syndrome. PMID- 1592562 TI - A historic profile of pediatric otorhinolaryngology. PMID- 1592564 TI - Correction of supernumerary nostrils. AB - Two rare cases of hypoplastic heminose associated with a supernumerary nostril are presented. In both cases a patent nasal cavity was present on the hypoplastic side. The hypoplastic heminose was reconstructed with the skin and the lining of the second nostril. PMID- 1592565 TI - Biotinidase deficiency: a rare cause of laryngeal stridor. AB - A case of a child with a biotinidase deficiency who had a laryngeal stridor as a leading symptom is presented. This rare disease is distressing for diagnosis but easily treatable, if recognized. This condition, unless suspect clinically, could easily be overlooked and unnecessary tracheotomy could be done. PMID- 1592566 TI - Olfaction. PMID- 1592567 TI - Development of the leech nervous system. PMID- 1592568 TI - Cellular and molecular physiology of alcohol actions in the nervous system. PMID- 1592569 TI - Short-term neurophysiological monitoring in multiple sclerosis bouts. Evaluation of steroid treatment. AB - Visual (VEP) and brainstem auditory (BAEP) evoked potentials (EP) were recorded in 21 multiple sclerosis (MS) patients in acute relapse before and after steroid treatment. VEPs were abnormal in 14/21 patients and BAEPs in 10/21 patients before treatment. In 4 patients with acute optic neuritis (ON), an improvement of VEPs paralleled clinical evolution in 3 cases. Substantial and contrasting changes in VEPs or BAEPs, with no clinical counterpart, were related to a spontaneous fluctuation of EPs in acute relapses of MS. These changes suggest frequent subclinical (multifocal and, possibly, sequential) central nervous system involvement in MS bouts. Group analysis showed nonsignificant changes in EP parameters before and after treatment. Our results indicate that evoked potentials (EPs) are of limited value for monitoring the short-term effect of steroid treatment in MS in bouts. PMID- 1592570 TI - Dysgraphia and selective impairment of the graphemic buffer. AB - We report the linguistic analysis of a case of pure dysgraphia whose features suggest a selective deficit of the graphemic buffer. We discuss the neuropsychological pattern in the light of theoretical models of the cognitive processes considered to underlie writing skills. PMID- 1592571 TI - Retraction-convergence nystagmus: clinical and radiological study of 4 cases of vascular origin. AB - Retraction-convergence nystagmus is a classic finding in extensive and bilateral lesions of the dorsal midbrain, usually neoplastic and, as such, considered to signal a poor prognosis. We report 4 cases of retraction-convergence nystagmus associated with Parinaud syndrome arising from circumscribed lesions of vascular origin--3 hemorrhagic and 1 ischemic--with a completely benign course. The neuroimaging study enabled us to identify involvement of the pretectal areas and posterior commissure as well as of the dorsomedial thalamic nuclei in all cases. It thus seems that one or more of these areas must be involved in the genesis of this nystagmus. PMID- 1592572 TI - Cardiovascular reflexes in patients with malignant disease. AB - Although some authors have reported clinical features of autonomic dysfunction in patients with malignant disease only a few systematic studies have been carried out. We have investigated the autonomic function of 48 patients with carcinoma or lymphoma by testing their cardiovascular reflexes, and compared their results with those of 62 healthy volunteers. Our patients showed a smaller increase in heart rate and a greater fall in blood pressure on standing up, as well as a smaller rise in blood pressure in response to contralateral handgrip. The study group showed a higher percentage of established sympathetic lesion (54.2% vs 27.4%, p: 0.008) and of atypical pattern of global autonomic function impairment (50% vs 24.2%, p: 0.03) than the control group. Our data suggest that patients with malignant disease suffer from a definite autonomic dysfunction. PMID- 1592573 TI - Total lymphoid irradiation in chronic progressive multiple sclerosis. AB - 6 patients with severe chronic progressive multiple sclerosis were subjected to total lymphoid irradiation (TLI) to assess clinical efficacy and side effects. During a 4 year follow-up the disability progression was continuous. Side effects during TLI were well tolerated; side effects after TLI brought about a worsening of the quality of life. One patient died of pneumonia. In this preliminary study TLI did not reduce the worsening of disability in MS patients. PMID- 1592574 TI - Slowly progressive familial dementia with recurrent strokes and white matter hypodensities on CT scan. AB - We describe 2 normotensive sisters presenting slowly progressive dementia associated with acute or subacute focal neurological symptoms, unilateral or bilateral motor signs, and dysarthria. Their father, who died in the seventh decade, had a similar clinical picture. Computerized axial tomography (CT) scan of the head showed symmetrical hypodensities in the periventricular white matter and mild to moderate hydrocephalus. In these patients a diagnosis of Binswanger's disease was based on the clinical features supported by white matter changes on CT scan. Our study suggests that genetic factors may play a role in the etiology of Binswanger's disease. PMID- 1592575 TI - Alzheimer-type dementia and verbal memory performances: influence of selegiline therapy. AB - In a double blind randomized crossover trial lasting 6 months selegiline, a selective MAO-B inhibitor, was tested against placebo for activity on verbal memory performances in Alzheimer-type dementia (DAT). Verbal memory was assessed with the Rey-Auditory-Verbal Learning Test at the start of treatment, at the time scheduled for crossover (90 days) and at the end of the trial (180 days). The results suggest that selegiline possesses significant activity on some memory parameters, which seems to depend on an improvement both in information processing abilities and in learning strategies at the moment of acquisition. PMID- 1592576 TI - The role of MRI in the diagnosis of olivopontocerebellar atrophy. AB - Under the term of olivopontocerebellar atrophy different nosological pictures are grouped, all characterized by showing clinical signs of deficiency of the structures of the pons and of the cerebellum. The diagnosis of olivopontocerebellar atrophy has been made, until now, by clinical criteria while typical anatomopathological changes are found at the autoptic studies. We describe three patients affected by olivopontocerebellar atrophy, of different types and at different stages of disease. In all cases MRI showed a similar and typical picture of atrophy of the olivary eminences of the medulla oblongata resulting in straightening of the angle usually present on the ventral frontier between pons and medulla oblongata. This diagnostic tool demonstrated thus to be of primary relevance yet in the early phases of the disease. PMID- 1592577 TI - Congenital generalized lipodystrophy associated with multiple sclerosis. AB - We report the case of a 22 year old woman with congenital generalized lipodystrophy who presented a left brachiocrural pyramidal hemisyndrome, bilateral cerebellar signs and a left cranial nerve VI deficit. The clinical pattern had a tendency to regress. MRI brainscan, CSF examination and clinical features led to the diagnosis of "probable demyelinating syndrome". Published data on CNS involvement in patients with congenital generalized lipodystrophy are few and we have found no cases in which a demyelinating syndrome is associated. In the case we report it is tempting to see the disorder of the lipid metabolism underlying the congenital generalized lipodystrophy as underlying the myelin disorder as well. PMID- 1592578 TI - Bickerstaff brainstem encephalitis. A case report. AB - A 33-year-old woman three weeks after a febrile illness presented with a syndrome of ophthalmoplegia, ataxia and areflexia (SOAA) that characterizes clinically both Bickerstaff and Miller Fisher syndromes. The normality of the electrophysiological tests performed, the CSF findings and the magnetic resonance images proved that the syndrome stemmed from brainstem pathology. PMID- 1592579 TI - Apomorphine in malignant syndrome due to levodopa withdrawal. AB - We report a case of neuroleptic malignant syndrome (NMS) following abrupt reduction of chronic levodopa treatment in a 71 year old female parkinsonian patient. The NMS resolved within 24 hours of the addition of apomorphine to levodopa therapy. PMID- 1592580 TI - Correlative head and neck imaging. PMID- 1592581 TI - Evaluation of the globe using computed tomography and magnetic resonance imaging. AB - This article is a review of computed tomography (CT) and magnetic resonance imaging (MRI) findings in three groups of pathological conditions of the globe: a) malignant tumors, b) benign tumors and vascular lesions, and c) miscellaneous conditions. MRI technical refinements and the use of gadolinium-DTPA as an enhancement agent provide better anatomic definition of the globe. However, CT remains the method of choice in the investigation of lesions with calcification and bone. In the group of malignant tumors, retinoblastoma, the most common intraocular tumor in childhood, is best diagnosed with CT; for malignant melanoma, the most frequently encountered primary intraocular malignancy in adults, MR is the imaging modality of choice; and for metastatic tumors to the eye, mainly carcinomas, CT and MRI do not show characteristic features. PMID- 1592582 TI - Comparative assessment of diseases of the orbit using computed tomography and magnetic resonance imaging. AB - Computed tomography (CT) and magnetic resonance imaging (MRI) are the modalities of choice in the assessment of inflammatory diseases, cysts, benign and malignant tumors found in the orbit. CT delineates, to greater advantage, bony structures and areas of calcification. MRI is superior to CT in visualization of the various soft tissue structures and in providing lesion characterization. The lesion location in the orbit is important: extraconal (frequently lymphomas), intraconal (most commonly cavernous hemangiomas and neurilemmomas), and optic nerve sheath (gliomas and meningiomas). The contours of the lesion are also significant: sharply delineated (benign), irregular, lobulated (lymphoma or lymphoid hyperplasia), or invasive (paranasal tumors). CT and MRI characteristics, in particular contrast enhancement, further contribute to the characterization of the various types of lesions within the orbit. PMID- 1592583 TI - Surgery of the anterior skull base: total ethmoidectomy for malignant ethmoidal tumors. AB - The authors report their 17-year experience of total ethmoidectomy using a combined rhinological and neurosurgical approach. As a result of new imaging methods significant progress has been made in the field of pre-operative topographic diagnosis as well as in the operative procedure itself. The optimal skull base reconstruction, which consists of epicranial graft and cryopreserved bone homograft, seems to reduce operative morbidity and mortality. The combined approach technique is shown to be successful in the treatment of both adenocarcinomas and olfactory bulb tumors. However, epidermoid carcinomas still have a poor prognosis due to frequent local recurrences and visceral metastases. PMID- 1592585 TI - Surgery of the internal acoustic meatus and the cerebello-pontine angle. AB - Tumoral and functional surgery of the cerebellopontine angle and the internal acoustic meatus has been performed in our department for more than 20 years. Acoustic neurinomas (700 cases operated to date) represent the great bulk of this surgery. Since 1985, we have drastically modified our approach to these tumors (220 cases). Large tumors are now dealt with, regardless of the patient's hearing, through a widened translabyrinthine approach. Small tumors with normal hearing are operated on through a suboccipital or a retrolabyrinthine approach depending on the tumoral extension in the internal acoustic meatus. The facial nerve function was preserved in 83% of the cases. Hearing was saved only 6 times in 45 attempts, despite 23 cases of apparent anatomical conservation of the cochlear nerve. Vestibular neurectomy, carried out through a middle cranial fossa or through a retrolabyrinthine approach, ameliorated vertigo in 95% of cases. The major operative risks are regressive facial paresis and secondary total deafness (10% of cases). Surgical treatment of facial hemispasm by neurovascular decompression is very effective, but not without risk. We now prefer to use botulin toxin therapy. PMID- 1592584 TI - Magnetic resonance imaging and computed tomography of the internal auditory canal and cerebellopontine angle. AB - Computed tomography (CT) and magnetic resonance imaging (MRI) assessment of internal auditory canal lesions focuses on acoustic neurinomas (Schwannomas), a small percentage of which are entirely intracanalicular. MR is now the imaging method of choice and allows for the detection of intracanalicular tumors as small as 3 mm. Acoustic neurinomas are isointense relative to the pons on MR T1 weighted images, mildly hyperintense on MR T2-weighted images, and enhance intensely after i.v. administration of gadolinium-DTPA. The radiologic evaluation of the cerebellopontine angle first addresses lesions of the angle itself, other than acoustic neurinomas. On CT, meningiomas show calcifications in 25% of cases and homogeneous enhancement in 90%; on MR they demonstrate homogeneous gadolinium DTPA enhancement. Epidermoids do not enhance on MR. Cholesterol granulomas are strongly hyperintense on MR T1- and T2-weighted images. Rare vascular lesions may mimic neoplasm in the posterior fossa and in the cerebellopontine angle: vertebral basilar dolichoectasia, vascular loop or aneurysm of the anterior inferior cerebellar artery. CT and MR characteristics of lesions extending into the cerebellopontine angle cistern are then reviewed: nonacoustic posterior fossa schwannomas, which have the same MR signal characteristics as the acoustic schwannoma; jugular fossa lesions, the most often encountered being the glomus jugular tumor; and rare intraxial posterior fossa tumors that extend into the cerebellopontine angle. PMID- 1592586 TI - Radiological evaluation of the facial nerve. AB - The methodology for evaluation of the facial nerve (CT and MR technique) is presented and the need for routine use of gadolinium-DTPA with MRI is emphasized. The various disorders causing facial palsy with their clinical and radiological features are described. Although tumors only cause 6% of facial nerve disorders, they require a thorough radiologic workup. Schwannoma is the most common neoplasm arising from the facial nerve and can occur anywhere along the nerve course: cerebellopontine angle and internal auditory canal, geniculate ganglion, or tympanic, mastoid and intraparotid segments. PMID- 1592587 TI - Parotid gland and parapharyngeal space imaging--the surgical significance. AB - Wise head and neck surgeons, for whom parotid gland surgery constitutes a substantial portion of their case load, make full use of the radiologist and cytologist in arriving at a rational pre-operative diagnosis. They utilize the skill of these allied consultants to qualify (by histology) and quantify (by staging) diffuse and mass lesions of the parotid gland (and subjacent parapharyngeal space) in order to evolve an effective surgical, radiation or other treatment plan. They understand the basic principles of diagnostic imaging and apply them to the clinical problem at hand. They minimize diagnostic and intra-operative "surprises", reduce intra-operative and post-operative complications and generally have a more "informed" patient and patient's family. The purpose of this manuscript is to discuss a contemporary role for diagnostic imaging in neoplastic (and other) diseases of the parotid gland and subjacent parapharyngeal space. Not all lesions of the parotid gland require imaging, although a pre-operative clinical photograph, including evidence of facial nerve function, is always welcome. Other lesions may need diagnostic imaging, from simple to complex and sophisticated, depending upon the problem. Properly used, effective and selective diagnostic imaging can improve the surgeon's confidence by providing a more realistic provisional diagnosis and a better pre-operative staging process and treatment plan, thereby avoiding the surgically unexpected and facilitating prognosis. PMID- 1592588 TI - Cystic lesions of the mandible and maxilla--radiological evaluation and differentiation. AB - Cystic lesions of the mandible and maxilla are easily recognizable with various imaging modalities: different conventional X-ray films, computed tomography and magnetic resonance imaging. In this article, the author defines and classifies the most-encountered kinds of odontogenic and nonodontogenic cysts and presents in each case the various parameters that should be analyzed in order to reach a radiological diagnosis: location of the lesion within the mandible, its relationship to adjacent structures, its shape, etc. Nevertheless, there remain cystic lesions that cannot be differentiated from benign and, occasionally, malignant lesions. In some of these cases, final diagnosis will be reached only after surgical intervention and histopathological examination. PMID- 1592589 TI - Scintigraphic evaluation of patients with thyroid carcinoma--therapeutic approaches. AB - The therapeutic approach to patients with differentiated thyroid carcinoma has become a major issue of controversy in the last decade. The major aspects are the surgical resection and adjuvant therapy, particularly the need for thyroid ablation following surgery. According to the risk group definition suggested by Cady in 1979, low risk patients may be subjected to lobectomy only, then placed on thyroxine treatment and followed clinically with thyroglobulin determination. High risk patients should undergo total thyroidectomy and 131I ablation. Follow up should include thyroxine treatment and an annual whole body 131I scan. In the event of residual thyroid tissue or functional metastases, 131I treatment is to be given. PMID- 1592590 TI - Ultrasonographic evaluation of neck masses--sonographic patterns in differential diagnosis. AB - Ultrasound is a relatively inexpensive, widely available noninvasive method of investigation. Although there is extensive documentation on the use of ultrasound in abdominal lesions, it appears to have been underutilized in the evaluation of neck masses. Ultrasound enables detection of thyroidal and extrathyroidal masses, and definition of their boundaries and their relationship to great vessels. The traditional and exclusive use of ultrasound to separate cystic from solid lesions is outdated. High resolution new-generation real-time machines allow recognition of secondary changes in the structure of basically solid or cystic masses. Infected cystic masses may give the impression of a solid neoplasm. Although partial or total necrosis within a lymph node may simulate a branchial cleft cyst, ultrasonography can in many cases recognize such a "cystic-looking" malignant lymph node and thus prevent a premature biopsy that could transform an initially curable disease into an incurable one. PMID- 1592591 TI - Scintigraphic techniques in pre-operative localization of parathyroid adenoma. AB - Solitary parathyroid adenoma is the most common cause of primary hyperparathyroidism. It can be removed surgically with a 92-96% success rate without any pre-operative imaging procedures. However, imaging procedures may be of help in localization, thereby reducing operative morbidity, and in the detection of ectopic adenomas. The decision to undertake surgical exploration should not be based on these procedures because of their low sensitivity and limited specificity when used alone, but rather on an established biochemical diagnosis of hyperparathyroidism. PMID- 1592592 TI - Decision making in thyroid and parathyroid surgery: the influence of imaging. AB - Surgical decision making is essentially based on experience, augmented by a management philosophy. In this manuscript we review concepts of thyroid and parathyroid surgical decision making in relation to diagnostic imaging input. These two endocrine glands have crucial anatomic associations, but very different pathologic conditions; it is the specific pathologic considerations that ultimately determine the decision-making process. For us, diagnostic imaging has enabled a more effective surgical decision-making process through thorough pre operative planning. The strategy for parathyroid surgery is based upon the pathologic localization obtained by high resolution ultrasound. Thyroid surgical strategy is more heavily influenced by experience, and our policy is total thyroidectomy for all malignant and benign tumors with airway compression. PMID- 1592593 TI - Pre-therapeutic evaluation of laryngeal carcinomas using computed tomography and magnetic resonance imaging. AB - A prospective and comparative computed tomography (CT)/magnetic resonance imaging (MRI) study on 90 patients with endoscopically examined and histologically proven laryngeal malignancy is presented. Post-operative pathological and intra radiological (CT vs. MRI) correlations are established. We conclude that MRI is the method of choice for staging laryngeal malignancies. PMID- 1592594 TI - Tracheal lesions--assessment by conventional films, computed tomography and magnetic resonance imaging. AB - The radiological evaluation of the trachea is comprehensive and includes lateral neck and anteroposterior high kilovoltage conventional X-ray films; fluoroscopy; barium study of the esophagus; angiography for vascular lesions; computed tomography (CT), which is of great value in assessing tumors that have penetrated the wall of the trachea; and magnetic resonance imaging (MRI), especially helpful in delineating the entire length of a stenosis or a tumor because of its coronal, oblique and sagittal views. The authors describe the etiologic, anatomic and clinical aspects of tracheal stenosis, and review benign and malignant tracheal tumors together with a description of their CT and MRI characteristics. PMID- 1592595 TI - Inflammatory lesions of the neck, including fascial spaces--evaluation by computed tomography and magnetic resonance imaging. AB - The clinical findings that characterize inflammatory lesions of the neck are briefly presented. The technique of the major imaging methods--computed tomography (CT) and magnetic resonance imaging (MRI)--used for the evaluation of these lesions is described as well as the radiologic appearance of abscesses, enlarged lymph nodes and cellulitis. The only advantage of MRI over CT is its multiplanar capability, sagittal sections being especially useful in the demonstration of the retropharyngeal space. PMID- 1592596 TI - Septic thrombophlebitis of the internal jugular vein. AB - Septic thrombophlebitis of the internal jugular vein is a rare condition with diverse etiologies. The significance of the systemic effects of this condition far exceeds its local implications. Complications occur frequently and may be life threatening. The pathogenesis, histologic features, clinical and imaging aspects of this entity, based on a series of 13 patients, are discussed. PMID- 1592597 TI - Contribution of nuclear medicine to the diagnosis and management of extracranial head and neck diseases (excluding thyroid and parathyroid). AB - Nuclear medicine contributes to the diagnosis and management of extracranial head and neck diseases through the physiological information it provides. In addition to thyroid and parathyroid indications, radionuclide studies, i.e., bone and 67Gallium citrate scans are helpful in diagnosing and treating head and neck malignancies. Positron emission tomography with 18F-fluorodeoxy-glucose evaluates tumor glucose metabolism before and after treatment. Triphase bone scintigraphy enables early detection of osteomyelitis of the skull base, and its management requires 67Gallium-citrate or 111Indium-WBC scintigraphies. Salivary gland scintigraphy is the only functional imaging test of salivary tissue and should be utilized more in the diagnosis of submandibular duct obstruction and in the evaluation of preserved parenchymal function after recurrent infections. PMID- 1592598 TI - Vascular evaluation of head and neck masses by magnetic resonance imaging. AB - The vascularity of head and neck masses and their relation to major vessels is an important factor in the differential diagnosis and surgical strategy. Magnetic resonance imaging (MRI) can be tailored to enhance vascular flow by making use of two flow phenomena--time of flight and phase. Fifteen patients with head and neck masses were evaluated by flight flow-sensitive MRI sequences. The inflow sensitive images were superior to standard unenhanced and gadolinium-enhanced spin echo images in the assessment of tumor vascularity. They were also useful in assessing the relationship of the head and neck masses to the adjacent vessels. The limitation of these inflow-sensitive sequences is the inability to differentiate flow from fat or subacute hemorrhage. Inflow-sensitive MRI obviates the need for diagnostic angiography in most head and neck masses. PMID- 1592599 TI - Indications for gadolinium-DTPA in magnetic resonance evaluation of extracranial head and neck mass lesions: review of experience with 27 patients examined with a 2 tesla imager. AB - The authors review their experience with 27 patients who underwent gadolinium enhanced magnetic resonance imaging (MRI) at 2 tesla. The contribution of the contrast agent was evaluated with respect to three properties--lesion conspicuity, margins and characterization. Gadolinium enhancement contributed most to the characterization of the lesion and helped to better define lesion margins in relationship to nonfatty tissues. It is concluded that gadolinium enhanced MR images frequently give significant additional information in the evaluation of head and neck mass lesions. PMID- 1592600 TI - Providing health care to Hawaii's elderly. AB - Hawaii's rapidly aging population is a challenge for Hawaii's health care providers. What with the high cost of care, limited health care resources, and a rapidly increasing population of frail elderly patients living in the community, will our medical practices be able to adapt to the care of patients who require more time and who will have not only multiple medical illnesses but complicated psychosocial conditions as well? Will our health care facilities be prepared for the typically longer stay and more expensive older patient? Will the cost of care in Hawaii keep on rising? Who will pay? Will this challenge turn into a crisis? PMID- 1592601 TI - Ciguatera, once again. PMID- 1592602 TI - Ciguatera: a review. AB - Hawaii State Department of Health epidemiological records were reviewed for cases of ciguatera poisoning for the entire state, from January 1984 through December 1988. During the 5 year interval, the numbers of ciguatera poisoning incidents, number of cases, and date of onset were recorded, as well as age and sex of individuals involved. The place of catch of each fish was noted as well as whether or not the fish was obtained commercially. The parts of the fish consumed were also recorded. A total of 150 ciguatera incidents occurred during this period, involving 462 individuals for an average annual incidence rate of 8.7/100,000 population. The 3 most frequently implicated species of fish were the Carangoides species (jack or papio or ulua), Ctenochaetus strigosus (surgeon fish or kole), and Aphareus furcatus (fork-tailed snapper or waha nui); however, more than 50 species of fish had caused one or more outbreaks. The most frequently implicated areas of the toxic fish were the Kona coast as well as the South Point of the island of Hawaii, and the Napali coast of the island of Kauai. Of the 150 outbreaks, 32 (21%) were related to commercial fish. The rest were related to sportfishing. PMID- 1592603 TI - Factors related to the provision of hospital discounts for HMO inpatients. AB - Using 1986 AHA hospital survey data, we analyzed hospital-HMO contract provisions, hospital operating characteristics, and market conditions for a national sample of 801 hospitals with HMO contracts to determine the factors related to provision of a discount and the magnitude of the discount if present. Seventy-eight percent of the hospitals reported that at least one of their HMO contracts provided a discount for inpatient services. Risk-sharing provisions, the number of hospitals within a five-mile radius, the proportion of the population enrolled in HMOs, and the number of HMOs operating in the metropolitan statistical area (MSA) were directly related to provision of discounts. Public hospitals were less likely than other facilities to provide discounts. For the magnitude of the discounts, risk-sharing provisions and the number of hospitals within a five-mile radius were again related, as was the number of HMOs operating in the MSA--but this time the number-of-HMOs variable had an inverse relationship. The results suggest that increased HMO market activity does result in price competition for hospital services but that hospital discounting strategies are extremely complex and may not follow conventional market theories. Hospitals appear to be using contracts both to stabilize their relationships with HMOs and increase market share, and they are increasingly giving discounts to achieve those ends. PMID- 1592604 TI - The discriminating characteristics of for-profit versus not-for-profit freestanding psychiatric inpatient facilities. AB - This study examines the characteristics that discriminate between ownership types among private, freestanding psychiatric inpatient facilities in the United States. Use of data from the Inventory of Mental Health Organizations (National Institute of Mental Health 1983, 1986), revealed that not-for-profits provide more services and serve more of the underinsured, while for-profits serve the better insured, concentrate primarily on inpatient services, and serve more children, adolescents, and substance abusers. A surplus bed capacity among for profit psychiatric hospitals is presumed to contribute to lower occupancy rates and less turnover in the for-profit sector. Not-for-profit psychiatric facilities are also found to be more involved in professional training and to be more accessible through emergency services. However, the misclassification test in the discriminant procedure reveals that a significant group of not-for-profit facilities looks more like its for-profit counterpart group than like other not for-profits. Study findings are interpreted both in terms of debates over the tax exempt status of not-for-profit hospitals and the potential negative service effects of proprietization. PMID- 1592605 TI - The effects of hospice coverage on Medicare expenditures. AB - This article reports on the findings of a study of the effects of the hospice program on Medicare Part A expenditures during the first three years of the program. The analysis compared treatment costs between hospice beneficiaries and nonbenefit patients with diagnosis of malignant cancer during their last seven months of life. It was estimated that during the first three years of the hospice program, Medicare saved $1.26 for every dollar spent on Part A expenditures. While the methodology included use of data from Medicare claims to adjust for confounding factors, including self-selection bias, our estimated savings might still have been overstated due to persistent selection effects. The extent of savings also varied according to the hospice's organization. Freestanding hospices, in contrast to those affiliated with either a hospital, nursing home, or home health agency, achieved the greatest savings by utilizing home care more extensively. However, we note that payment rates are increasing and the limits on the benefit period are being lifted, making it possible that the savings related to the hospice program found in this study will not continue. Of greater importance may be the long-term access and quality effects engendered by the benefit's preference for home care. PMID- 1592606 TI - The learning curve and the cost of heart transplantation. AB - The effect of learning on hospital outcomes such as mortality or adverse events (the so-called "practice makes perfect" hypothesis) has been studied by numerous investigators. The effect of learning on hospital cost, however, has received much less attention. This article reports the results of a multiple regression model demonstrating a nonlinear, decreasing trend in operative and postoperative hospital costs over time in a consecutive series of 71 heart transplant patients, all treated in the same institution. The cost trend is shown to persist even after controlling for various preoperative demographic and clinical risk factors and the specific experience of individual surgeons. Using a reference case, the model predicts a cost of $81,297 for the first heart transplant procedure performed at the hospital. If this same patient had been the tenth case rather than the first, with the hospital having benefited from the experience gained in nine previous cases, the model predicts the cost would now be only $48,431, or approximately 60 percent of the cost of the first case. Had this patient been the twenty-fifth case, the predicted cost would be $35,352 (43 percent of the original cost), and had this been the fiftieth case, the cost would be $25,458 (31 percent of the original cost). The longitudinal study design used in this analysis greatly reduces the likelihood that the observed cost reduction is due to economies of scale rather than learning. The results have implications for a policy of regionalization as a tactic for containing hospital cost. Whereas others have pointed to a volume-cost relationship as an argument for the regionalization of expensive and complex hospital procedures, the present data isolate a learning-cost relationship as a separate argument for regionalization. PMID- 1592607 TI - Fairness in prospective payment: a clustering approach. AB - Problems of fairness in prospective payment have existed since the inception of this regulatory method in the early 1980s. While prospective payment ostensibly has sought to reward efficient producers and provide disincentives for inefficient producers of health care, many hospitals have been penalized financially as a consequence of facing systematic factors beyond their control. This article defines homogenous peer groups of Department of Veterans Affairs providers for the purpose of establishing competitive prospective reimbursement rates. An econometric analysis classifies hospitals into six categories: small affiliated, small general, midsize affiliated/tertiary, large affiliated/tertiary, midsize general, and psychiatric. The Department of Veterans Affairs adopted this classification to alter its prospective payment system in 1988. PMID- 1592608 TI - Health practices of critical care nurses. AB - Little is known about the health practices of critical care nurses (CCNs). Because their health behaviors may influence their inclinations to counsel patients, it is important that CCNs engage in a healthy lifestyle and serve as health exemplars. The purpose of this survey was to describe the health practices of 499 CCNs. Data were gathered by questionnaires that elicited information regarding smoking habits, oral health and dietary practices, energy expenditure, seat belt use, alcohol consumption, and health surveillance behaviors. This article is a sequel to a previous manuscript that reported findings relative to the smoking practices of CCNs. Results of the study suggest that the CCNs surveyed were not fulfilling their roles as health exemplars. Although some reported favorable health practices, many indicated habits that were less than desirable. These data document the need to develop strategies for improving the health behaviors of CCNs, thereby protecting their future health. Ultimately, these strategies may benefit their patients. PMID- 1592609 TI - A theoretic perspective on postcode stress experienced by critical care nurses. AB - Death and dying are among the factors that produce stress in critical care nurses. Resuscitation attempts, often associated with dearth and dying in critical care areas, also predispose to stress. However, a dearth of information exists in the literature concerning the psychologic impact of resuscitation on critical care nurses. To promote scholarly thought and dialogue, role theory is applied as a framework to comprehend stress in relation to resuscitation attempts. Information from published literature, the theoretic framework, and the authors' clinical experiences and observations are synthesized to provide suggested guidelines for postcode conferences to reduce critical care nurses' stress in the postresuscitation period. PMID- 1592610 TI - Computer-controlled sodium nitroprusside infusions in patients after cardiac surgery. AB - Postoperative hypertension, a common occurrence after cardiac surgery, is frequently controlled by sodium nitroprusside infusions. Computer-controlled administration of this drug has been shown to be superior to manually controlled systems for maintaining the patient's blood pressure within an optimal range. The impact of this technology on patients, nurses, and hospitals is discussed. PMID- 1592611 TI - The efficacy of inpatient education after myocardial infarction. AB - Nearly half a million Americans will survive an acute myocardial infarction (MI) this year. Nurses often question whether patients who have had an MI are able to absorb, retain, and use information given in the hospital. This review examines the research literature on inpatient education after MI published between 1975 and 1989 to determine (a) what information patients identify as most important, (b) whether inpatient education increases patients' knowledge, (c) whether anxiety prevents or diminishes learning in this setting, (d) whether inpatient education is able to produce lifestyle changes after discharge, and (e) which teaching methods are most effective. Patients identified risk factors as their primary concern. Most studies showed patients were able to learn new information, despite the presence of anxiety, particularly regarding activity after discharge. Inpatient education also stimulated some life-style change after discharge, most frequently in the areas of activity and smoking cessation. Several types of teaching methods were compared; audiovisual methods were found to be at least as effective as one-to-one patient teaching. PMID- 1592612 TI - A nursing guide for patient care after percutaneous cardiopulmonary support. AB - Information is presented about a relatively new procedure being used in the critical care area. The percutaneous insertion technique for the initiation of cardiopulmonary bypass support (PCPS) has given new hope for patients who are considered high risk for elective coronary angioplasty and to those who suffer cardiopulmonary arrest in the cardiac catheterization laboratory or critical care unit. The initiation process of cardiopulmonary bypass support and the criteria for elective cases are reviewed and two case studies follow. Specific attention is given to the immediate postprocedural phase, where nursing responsibilities and prioritization of patient care are addressed. A nursing care guide is included. PMID- 1592613 TI - Nursing care requirements of patients with DNR orders in intensive care units. AB - The purpose of this study was to examine the differences in demographic characteristics and nursing care requirements of patients with and patients without DNR (do not resuscitate) orders in intensive care. The sample consisted of 62 patients with and 62 without DNR orders from the intensive care units of three community hospitals. Data were collected until patients recovered and were transferred from the unit or until death occurred. Data were analyzed by chi square tests for homogeneity, t tests, and analysis of covariance. Patients with DNR orders were white (p = 0.015), older (p = 0.03), more likely to reside in nursing homes (p = 0.04), had longer intensive care stays (p = 0.0005), were more likely to be admitted from another nursing unit (p less than 0.001), and had higher mortality rates (p less than 0.001). In intensive care settings, patients with DNR orders received more nursing care than patients who did not have DNR orders. PMID- 1592614 TI - Critical care management of the patient with HIV infection who has Pneumocystis carinii pneumonia. AB - Pneumocystis carinii pneumonia (PCP) is the most frequently occurring opportunistic infection in individuals infected with the human immunodeficiency virus. Improved methods of diagnosing and treating PCP have resulted in increased survival rates. Nurses are more frequently faced with treatment of the critical care patient with PCP. Knowledge about the mechanisms and manifestations of PCP as well as its diagnosis and treatment provides a baseline for the nursing management of PCP. Nursing care for the critically ill adult patient with PCP focuses on the management of the human responses to PCP including hyperthermia, impaired gas exchange, altered respiratory function, fatigue, and altered nutrition, and on the management of the side effects of treatment including nausea, vomiting, and hypoglycemia. Effective interventions related to these patient problems can improve the quality of care and ultimately affect patient outcomes. PMID- 1592615 TI - Popliteal artery entrapment syndrome: implications for nursing care. AB - Popliteal artery entrapment syndrome is an extremely rare phenomenon, with only 249 cases in the English literature over the past 30 years. Obstruction of the popliteal artery caused by abnormal anatomic development results in diminished blood supply to the extremity. Unlike more common vascular problems, this syndrome often produces claudication and symptoms of arterial insufficiency in young, healthy, even athletic individuals with no other apparent vascular risk factors. Accurate assessment and monitoring are critical in identifying this syndrome, minimizing complications, and preventing long-term adverse effects on activities of daily living. PMID- 1592616 TI - Positional oxygenation changes in air-transported neonates. AB - The effect of position on oxygenation was compared in 24 critically ill, premature neonates during pressurized, fixed-wing transport. The purpose of the study was to assess if there is a significant change in the arterial oxygen tension in the supine, prone, or prone-free positions during air transport. Neonates with endotracheal tubes in place who (1) had radiologic evidence of hyaline membrane disease, (2) had an umbilical artery catheter in place, and (3) required at least 1 hour of air transport to a level III intensive care center were admitted into the study after parental consent. There was an average 8% increase in oxygenation in the prone and prone-free positions when compared with the supine position. Although this difference might be considered clinically significant for the critically ill premature neonate, there was no statistically significant difference in arterial oxygen tension among the three positions tested in this study. PMID- 1592617 TI - Acute methanol poisoning: a case study. AB - Acute methanol poisoning produces severe anion gap metabolic acidosis caused by the toxic accumulation of metabolites, primarily formic acid. Formic acid produces serious neurologic sequelae. Therefore, an understanding of the mechanism of toxicity, treatment, and clinical course is essential in preventing permanent neurologic dysfunction. Prompt recognition and treatment are the keys to successful patient outcomes. This article presents a case report of a patient with severe methanol poisoning with clinical course, treatment, and outcome. PMID- 1592618 TI - Clinical markers of asthma severity and risk: importance of subjective as well as objective factors. AB - The purpose of this study was to explore patient perceptions of asthma severity and danger from asthma, correlate them with objective measures, and assess the impact of psychologic variables on the perception of severity. Recognition of patients at greatest risk for fatal attacks requires identifying those with severe asthma. In our study of 95 adults with asthma, we found that the subjective factors of perceived severity and perceived danger and the objective factors of medications, hospitalizations, history of intubation, and pulmonary function were important markers of asthma severity and risk. Our findings indicate that asthmatic adults make independent self-assessments that generally correlate with objective markers of increased risk of mortality and increased severity of the asthma. The perception of high severity was significantly correlated with depression, panic-fear, frequency of emergency department visits, and with an objective index of risk of death. The latter includes variables obtainable from history alone (number of medications to control symptoms, need for prednisone, prior intubation, and prior recent hospitalization) and is correlated with spirometric indexes of airflow obstruction, occurrence of nocturnal symptoms, and number of emergency department visits. PMID- 1592619 TI - Physiology of thirst and drinking: implication for nursing practice. AB - Thirst and drinking function to maintain body water balance and are basic to survival. Thirst is often associated with a dry unpleasant-tasting mouth and the feeling of a need to obtain water; it can result from dehydration, decreased vascular volume, dry mouth, pharmacologic agents, or inappropriate activation of the thirst mechanism. Drinking involves the motor activities that culminate in ingestion of liquids. Thirst sensation and drinking are influenced by many factors, including the temperature and taste of a liquid. Thirst may be discomforting in persons with limited fluid intake, diminished in some elderly persons, and inappropriate in persons who are compulsive water drinkers. Although nurses are commonly confronted with client complaints of thirst, there has been minimal nursing research that relates to assessment of thirst and drinking behaviors, nursing diagnoses for thirst, or nursing interventions for persons with altered thirst or drinking behaviors. PMID- 1592620 TI - Postoperative Serratia marcescens endophthalmitis. AB - Endophthalmitis after ophthalmic surgery is a rare but serious complication. Postoperative endophthalmitis presents clinically with conjunctival erythema and lid edema with eye pain and decrease in visual acuity. Diagnosis requires invasive culture techniques because postoperative external eye cultures are not reflective of intraocular organisms. The most common pathogens causing postoperative endophthalmitis are staphylococci and streptococci. Less common organisms associated with exogenous endophthalmitis include gram-negative aerobic bacilli and fungi. We report a case of Serratia marcescens postoperative endophthalmitis in a normal host. PMID- 1592621 TI - Care-giver suffering in critical care nursing. PMID- 1592622 TI - Noncardiac surgery in the patient with heart disease. PMID- 1592624 TI - [Long-term follow-up of acute pancreatitis--significance of cholecystectomy for the biliary form]. AB - Of 83 patients with acute pancreatitis it was possible to control 79 of them 5-16 years later, 33 on the basis of case histories and 46 personally. In 43 cases (54.4%) it was pancreatitis caused by gallstones. After an operative procedure, there followed in each case an auspicious progress without recurrence. By the patients who were not operated, there was a recurrence rate of 45.5%. In cases of pancreatitis not caused by gallstones the late progress is marked by a high recurrence and complication rate. PMID- 1592623 TI - [Acute pancreatitis in the rat following experimental microembolism with cholesterol crystals]. AB - Several case reports exist which demonstrate cholesterol crystals to be the cause of acute pancreatitis in humans. The crystals have been found intravascularly in the pancreas and at least in one case the origin of the crystals was known. We have undertaken to experimentally reproduce this pathogenetic mechanism in the rat. 30 rats were subjected to the following procedures: under anaesthesia the splenic artery was distally ligated and proximally cannulated; 16 control animals were injected via the cannula with saline (8 rats), particle free cholesterol saturated physiologic saline (3 rats) or nothing (5 rats). 14 rats were injected with ca. 400 microliters of a dilute suspension of cholesterol crystals of 5-40 microns diameter in cholesterol saturated physiologic saline. The abdomen was closed and after 24 h all animals were killed. Acute pancreatitis was diagnosed in all animals that received cholesterol microcrystals and in none of the controls. The diagnosis was based on macroscopic and histological findings. Acute pancreatitis was of focal, disseminated, necrotic type with oedema and moderate haemorrhage and fat necrosis. Only those parts of the pancreas were affected which were supplied by branches of the distal splenic artery used for retrograde injections of cholesterol crystals. This model supports the notion that microembolic or microthrombotic events play a pivotal role in the pathogenesis of spontaneous acute pancreatitis. PMID- 1592625 TI - [Therapy of acute pancreatitis]. AB - From 1973 to 1990 190 consecutive patients were admitted to the department of surgery of the Stadtspital Waid, Zurich, with a diagnosis of acute pancreatitis. 53 patients received conservative treatment, 93 patients with acute pancreatitis thought to be due to gallstones underwent cholecystectomy, in 23 cases combined with choledochotomy. 44 patient underwent pancreatic surgery. 10 diagnostic laparotomies, 14 necrosectomies, 6 pancreatic left resections and one subtotal pancreatectomy were performed. 9 pseudocysts and 4 pancreatic abscesses had to be drained. Over all mortality for operated patients was 29.5%, exceeding 50% for patients with operation within the first week of the disease. During the first ten years of our study we performed operations earlier and more often than in the following years (26 versus 17%). This more conservative management resulted in a marked reduction of mortality and complications. Today we try to control the first 8 to 10 days of the attack by intensive care and postpone pancreatic operations whenever possible to the second week. PMID- 1592626 TI - [Necrosectomy and laparostoma as a surgical therapy concept of acute necrotizing pancreatitis]. AB - 121 patients with acute necrotizing pancreatitis were treated according to a surgical regimen of necrosectomy, drainage by laparostomies and repeated revisions. Changing the protocol from revisions on demand to scheduled reexplorations resulted in an improvement of mortality from 53% to 28%. The high incidence of gastrointestinal fistulas (30%) associated with this regimen could be decreased to 5% by a more individual protocol with longer intervals of revisions in the later course. Mortality was 21% following this regimen. PMID- 1592627 TI - [The Frey operation: a valuable enrichment of therapeutic possibilities of chronic calcifying pancreatitis]. AB - Frey's duodenum-preserving resection is one of three techniques of conservative surgery for the relief of pain in chronic calcifying pancreatitis of the pancreatic head described since 1985 [2, 3, 7]. In our view Frey's procedure is the most satisfactory of the three techniques. It does not require transsection of the pancreas and is suitable to deal with ductal stenoses and stones not only in the pancreatic head but also in the body and tail of the pancreas. We have been impressed by the quality of pain relief obtained and by the smoothness of the postoperative course following this operation. Duodenum-preserving resection of the pancreatic head is greatly facilitated by the use of the ultrasonic dissector which permits dissection in a nearly bloodless field and is particularly suitable for achieving decompression of the intrapancreatic part of the common bile duct by dissecting anyway fibrosed and calcified tissue. The techniques of duodenum-preserving resection of the head of the pancreas are based on principles which have stood the test of time. They have, however, been introduced only a few years ago, and their role in the treatment of severe pain associated with chronic pancreatitis yet awaits more precise definition. PMID- 1592628 TI - [Hemorrhage-induced rupture of the pancreatic pseudocyst]. AB - Hemorrhage from pseudocyst may be the most serious complication of chronic pancreatitis: the mortality from such hemorrhage approaches 80%. The bleeding arises from a major artery--the artery is eroded by the basic process of autodigestion, and the pseudocyst is converted into a pseudoaneurysm. The wall of the pseudoaneurysm is subjected to arterial pressure and may perforate into the peritoneal cavity, an adjacent segment of the gastrointestinal tract, or the pancreatic ductal system. Clinical signs and indications of complicated pseudocyst are sudden abdominal pain, hypotension, sudden increase in abdominal tenderness, decrease of hematocrit and sudden disappearance of the mass. Sonography, CT and angiography accurately define the bleeding lesion and greatly aid in planning operative strategy. Surgery, angiographic embolisation, or a combination of both may be employed. Transcystic arterial ligation and internal drainage of the pseudocyst or distal pancreatectomy are the operative procedures of choice and give the best results. PMID- 1592629 TI - [Use of ultrasound in the surgical emergency unit]. AB - The sonography is very important diagnostic method for the abdominal emergency cases. This diagnostic screening method should be available in the surgical emergency station. Liquid, abscesses, organ ruptures and also many inflammations can be diagnosed with this not invasive method. It is our opinion that a training program in sonography should be available for young surgeons for the judgement of the abdominal emergency cases. PMID- 1592630 TI - [Prospective study of the early postoperative course of splenic rupture: spleen preservation versus splenectomy]. AB - The haematological and immunological changes after splenectomy have been the subject of intensive research in recent years. As a consequence there has been a clear trend towards splenic salvage. Due to the availability of improved diagnostic investigations (sonography, CT) nonoperative treatment with close observation has become increasingly important in adults. 75 patients with documented splenic injury were prospectively evaluated over a 45-month period with an emphasis upon splenic preservation. Unstable patients had operative exploration with attempt at splenorrhaphy or partial splenic resection. Stable patients were managed nonoperatively, regardless of the degree of splenic injury as determined by sonography and/or computed tomography. In 38 patients the spleen was preserved by operative preservation in 20 and nonoperative treatment in 18 patients. 37 patients required splenectomy. Four patients were managed initially by nonoperative treatment, but required exploration for secondary rupture at 7, 7, 10 and 13 days. Delayed splenectomy was performed in three patients and one patient was treated by splenorrhaphy 7 days after admission. Bleeding complications occurred in one patient after splenorrhaphy (bleeding from the pancreatic tail) and the bleeding vessel could be transfixed during the same anaesthetic. Four patients required reexploration after splenectomy for hemorrhage (2) and evacuation of infected haematomas. The Injury Severity Score (ISS) of the splenectomy and splenic preservation group was determined. Splenectomised patients showed in the postoperative follow-up a significantly increased infection rate (40%, p less than 0.02) when compared to patients with splenic preservation (10%) or nonoperative treatment (11%), even when they were matched in respect of multiple trauma using the Injury Severity Score (ISS). PMID- 1592631 TI - [Splenic abscess: therapeutic options]. AB - Pyogenic splenic abscess is a rare condition that tends to occur in patients with underlying often infectious diseases. The sensitivity of ultrasonography and computerized tomography has improve early diagnosis and follow-up. In our hands, splenectomy remains the therapy of choice, but we report the resolution of two uncomplicated splenic abscesses with antibiotics alone. PMID- 1592632 TI - [Delayed dysphagia after sclerotherapy of esophageal varices. Review]. AB - 167 of 189 patients were followed prospectively after sclerotherapy of oesophageal varices between 1982 and 1989. 18% developed a stenosis of the lower oesophagus causing dysphagia: 3 of these 30 strictures were malignant and 27 were benign. The former are probably not related to sclerotherapy. 17 of the latter responded to a modified diet and the other 10 required endoscopic dilatation. This was done successfully on an out-patient basis without complication in all cases. We conclude that dysphagia after sclerotherapy of oesophageal varices is common; it is usually caused by a benign stricture: if severe, it responds to endoscopic dilatation. PMID- 1592633 TI - [Prospective analysis of infections of the upper extremity]. AB - In a prospective investigation infections of the upper extremity are examined with respect to incidence, bacterial pathogens, operative or conservative treatment, and duration of disability for work. A total of 255 patients (pts) (170 men, 85 women; mean age 37 years, range 16-85) were entered into the study. In a 12-month period 163 (64%) were treated as outpatients, the condition of 92 pts (36%) required hospitalisation. Conservative and operative treatment was performed in 82 (32%) and 173 (68%) pts, respectively. Conservative treatment included fixation by cast as well as antibiotics (penicillinase resistant penicillin), usually given by the oral route for a mean of 4 days. Surgical procedures consisted of excision and debridement. Intraoperatively intravenous antibiotics were instituted for a mean of 3 days, followed by oral application for another 4 days. In 135 of 173 pts who underwent surgery, sufficient material for bacterial culture was obtained. There was a polymicrobial infection in 50% of pts. Most common isolated pathogens were Staphylococcus aureus, beta-hemolytical streptococci group A, and indigenous skin flora in 34%, 21%, and 11%, respectively. Among the 255 pts there were 26 HIV-positive iv drug abusers, who suffered from abscesses at injection sites. The infections in these immunocompromised HIV-positive pts did not reveal differences with respect to number and species of isolated pathogens as compared to immunocompetent pts. Resistant bacteria were not found. Response to treatment was satisfactory usually within a few days in all but 12 pts (4.7%) in which the failure could be attributed to inadequate primary debridement. PMID- 1592634 TI - [Who should be hospitalized following mild craniocerebral trauma?]. AB - The frequency of minor closed head injuries is high. These injuries may be complicated by the development of life-threatening intracranial hematomas. A well defined selection criteria for admission must be proposed to guarantee an efficacious observation. In our series of 489 hospitalized patients with a GCS of 15 when seen in the emergency room: 4 patients required evacuation of an intracranial hematoma, 11 revision of a depressed skull fracture or a compound fracture of base of the anterior fossa. Using the existence of a skull fracture as a selection for admission, a strategy proposed by Jennett and colleagues, it would have been possible to reduce the number of patients hospitalized by 70% without missing a patient who developed an intracranial hematoma. Following these criteria no intracranial hematoma would be missed in our patients with a GCS of 15. We suggest that the use of plain x-rays to identify skull fractures and subsequent hospitalization prevents missing an intracranial hematoma. Those patients with diminished levels of consciousness of focal neurologic deficits require admission irrespective of skull fractures. PMID- 1592635 TI - [Can humerus shaft fractures be treated with osteosynthesis?]. AB - The treatment of fractures of the humerus shaft is still controversial. The results of functional treatment (brace) are good, consolidation occurs in most cases within 8-10 weeks, slight malalignment can be accepted, and there is no risk of postoperative complications like osteitis, neurological iatrogenic disorders and technical errors. On the other hand a correct osteosynthesis allows painless functional postoperative treatment, the patient comfort is excellent and a selected group of patients might return to work faster. We present the results of plate fixation of humerus shaft fractures in 127 patients, operated from 1980 to 1988. 102 patients were clinically and radiologically controlled after 1 year: 85 patients (83.4%) presented an excellent or good result with complete functional recovery. 17 patients (16.6%) showed a limited range of motion in shoulder and/or elbow mostly due to other fractures of the same arm or to persistent neurological disorders (plexus or radial lesions). Postoperative complications included 2 postoperative radial palsies recovering completely within months, 5 failures of internal fixation due to technical errors, 2 pseudarthrosis and 4 postoperative infections, healed by reoperation and early removal of the implant with one exception (osteitis). We therefore conclude, that a correct plate fixation of humerus shaft fractures is an alternative to conservative treatment. The main advantage is better patient comfort and shorter disability for a selected group of patients. PMID- 1592636 TI - [Proximal femoral fractures. Is there an indication for the condylar screw (DCS)?]. AB - Between 1983 and 1989 66 consecutive fractures of the proximal femur were treated with a condylar screw DCS. 42 patients were available for a follow-up study, 12 subtrochanteric fractures (mean age 58.5 years) and 30 intertrochanteric fractures (mean age 73 years). The primary union rate was clearly higher in the subtrochanteric group (10/12) compared to the intertrochanteric group (22/30). All the 8 implant complications (pull-out, metal fatigue) in the intertrochanteric group were associated with important posteromedial comminution in elderly patients who cannot be mobilized with only partial weight bearing postoperatively. Unstable intertrochanteric fractures in elderly patients should not be treated with the DCS. These are indications for the DHS which allows controlled telescoping. The indication for the DCS is limited to proximal shaft fractures in younger patients capable of partial weight bearing. PMID- 1592637 TI - [Treatment civilian gunshot fractures of the femur shaft]. AB - 35 consecutive cases of fractures of the femoral diaphysis due to gunshot wounds (GSW) treated at Jackson Memorial Hospital of the University of Miami between January 1988 and February 1990 were reviewed. There were 32 low velocity and 3 high energy transfer wounds. The treatment protocol for low velocity GSW consisted of 3 days i.v. antibiotics, balanced skeletal traction (for logistic reasons) and delayed closed intramedullary nailing. There was no formal debridement performed. 3 out of 32 patients declined any operative intervention. The remaining 29 patients were treated according to the above protocol. 12 patients could be followed until complete osseous consolidation. In this group the only complication consisted of one late infection. 17 patients were lost to follow-up before complete consolidation. Out of this group, 8 showed advanced fracture callus formation on the last radiograph available, whereas 9 patients were lost to follow-up almost immediately after discharge. Since GSW victims were generally uninjured and treatment of indigent patients in the Miami area is declined by all other hospitals, we assume that there were non major complications even in the group of patients lost to follow-up. We therefore conclude, that intramedullary nailing of low velocity gunshot fractures of the femoral diaphysis without formal debridement is the treatment of choice under civilian circumstances. PMID- 1592638 TI - [The open femoral fracture in war--173 external fixators applied to the femur (Afghanistan war)]. AB - During the three years 1988 through 1990, more than 700 external skeletal fixations (AO/ASIF Tubular System) were utilized at the ICRC Hospital for Afghan War Wounded in Peshawar, Pakistan, 173 of which were for femoral fractures. 13% of the fractures were open grade II, and 71% open grade III, mostly due to high velocity gunshot or shrapnel injuries. Usually, the external fixator was left in place until consolidation of the fracture. The average time of external fixation was 128 days. Three major groups of complications have been observed: fracture complications, implant complications, and residual loss of function of the knee joint, probably the most significant permanent complication to the patient. In order to improve the functional results in treating open fractures of the femur, three measures are recommended: unilateral frame with posterolateral insertion of Schanz screws, postoperative positioning of the patient with 90 degrees of flexion of hip and knee joints and mobilization of the patient as soon as possible (on the first or second postoperative day). PMID- 1592639 TI - [Is implantation of a unipolar femoral endoprosthesis obsolete?]. AB - The authors are presenting a retrospective study of the long-term results of 702 femoral cephalic endoprostheses (451 unipolar and 251 bipolar prostheses). The mean age of the patients at operation was 80.1, in the majority of the cases the indication was a fracture of the femoral neck. The average follow-up was 33 months for the unipolar, and 24 months for the bipolar prostheses. The rate of reoperations is similar in both series, but the rate of dislocations is slightly lower for the unipolar prostheses. 82 patients (out of 120 surviving) have been controlled with an average follow-up of 6.51 and 4.76 years. The unipolar prostheses have a lower average New Mayo Hip Score (58.5 vs. 68.2). Radiologically, there are 7 acetabular protrusions in the group of unipolar prostheses and none in the other group. If both types of prostheses have their place in surgery of the hip, the authors recommend to implant bipolar prostheses in younger and more active patients, where a survival of many years is expected. PMID- 1592640 TI - [The gamma-nail as a resilient alternative to the dynamic hip screw in unstable proximal femoral fractures in the elderly]. AB - In a prospective randomised trial between September 1989 and June 1990 one hundred patients with per- and subtrochanteric fractures were consecutively treated by gamma-nail or DHS. The average age of both groups was about 80 years. The operation time for gamma-nailing was longer than for DHS implantation and also the postoperative blood loss was higher in the gamma-nail group. We found no difference of intraoperative blood loss, of perioperative lethality and in duration of hospital care. 90% of gamma-nail patients and 80% of DHS patients were successfully able to walk four days after operation with full weight bearing on the operated limb. Three patients in the DHS group with unstable fractures got cranial perforation of the cephalic screw mobilisation. Five patients of the gamma-nail group were reoperated, one case because of missed distal locking, one because of cranial perforation of the cephalic screw after varus dislocation of the proximal fragment. One patient suffered intraoperatively a proximal femur shaft fracture which was corrected during operation. In one case a wound hematoma was evacuated, an other patient needed secondary wound closure. Despite technical imperfection of implant and instruments, we conclude that the gamma-nail allows a very high percentage early and full weight bearing immediately after operation. So we consider that in the treatment of unstable pertrochanteric fractures of geriatric patients, the gamma-nail has proven to be more efficient than the DHS. PMID- 1592641 TI - [Bone segment transport in femoral defects. Animal experiment study]. AB - The aim of our experimental study was to realize the Ilizarov concept using a reamed intramedullary interlocking nail with an internal transport system. In 8 mature dogs a bone defect of 3 cm was performed at the femur. A distally osteotomized bone fragment (length 3.5 cm) was lowered through the bone defect. 4 times we had to exclude the animal from the evaluation. In this case the interlocking nails were broken within 6 weeks. In 3 dogs a regeneration of bone was found in the defect. In 6 dogs a deep infection along the transport system had developed. PMID- 1592642 TI - [Prosthetic cement: a vital risk?]. AB - This study analyses the causes of early death among 17/702 patients which received a hip endoprosthese following a fracture of the femoral neck. Among other patients we conducted 25 endoesophageal cardiac ultrasonographies during elective total hip replacement. There is only a bad correlation between the occurrence of embolies and using of cement. Other factors, as the effraction of the medullary canal and the rise of the intramedullary pressure, are important. PMID- 1592643 TI - [Follow-up of abdominal surgery by analysis of pH, p02 and pCO2 in drainage fluid]. AB - Milieu factors such as pH, pO2, and pCO2 have previously been shown to permit reliable intraoperative discrimination of infected and non-infected peritoneal or drainage fluid. The presence of infection was associated with pH less than 7.1, pO2 less than 6.5 kPa and pCO2 greater than 8 kPa. These variables were monitored in the immediate postoperative period to quantify clinical improvement and to evaluate their potential for the early detection of infective complications. 21 patients underwent laparotomy for intraabdominal infections such as perforated appendicitis or perforated sigmoid diverticulitis. 5 were operated on for reasons other than infection. Fluid was sampled from a drainage tube every second day for a mean period of 7 days for determination of pH, pO2, and pCO2. A score ranging from 0 (normal) to 6 (severely ill) was calculated from these measurements. Specimens were obtained intraoperatively from 14 patients with documented infections and their mean score averaged 5 (range 3-6). Specimens were obtained on days 4 and 6 from 18 patients whose progress was uneventful and their mean score was 0.3 (range 0-2). 4 of these 26 patients developed postoperative infections after anastomotic breakdown, and each of their scores increased 1-2 days before the infection became clinically obvious, reaching values ranging from 3-6. In contrast, only 1 of 18 patients who made uneventful progress scored greater than 2 after day 3 (p less than 0.01). We conclude that assessment of milieu factors in peritoneal or drainage fluid permits quick and easy monitoring of the postoperative course. PMID- 1592644 TI - [Origin of secretions after denervation of the small intestine in the dog]. AB - The origin of the severe diarrhea appearing after intestinal denervation or transplantation was studied on the 3rd and 14th postoperative days in 5 groups of dogs undergoing total or partial denervation. The net movements of water and electrolytes were investigated by employing an experimental model of intestinal perfusion in isolated loops in vivo. The active uptake of phenylalanine and beta methylglucoside and Na(+)-K(+)-ATPase activity were used for in-vitro evaluation. Bacteriologic and histological specimens were also taken. Following total denervation with anastomosis, a considerable loss of water and electrolytes as well as numerous E. coli were found in the entire small intestine. This net secretion is due to the stagnation of bacteria in the presence of complete denervation and the absence of food since the animals in this group could not eat properly following general anesthesia and surgery. Consequently, peristalsis was not stimulated and bacterial overgrowth occurred. In the group denervation with pseudo-anastomosis, perfusion studies showed a decrease of absorption in the jejunum and minimal but significant secretion in the ileum. A high number of E. coli was also present. Since the mucosa remained intact, nutrition per os was resumed in the immediate postoperative period and excessive water and electrolyte loss was avoided. The high number of bacteria was due to a decrease in intestinal motility since complete denervation was performed. In the denervation group, water and electrolyte movements were identical to those observed in the preceding group but the entire intestine remained sterile.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592645 TI - [Mechanical preparation of the colon with sodium picosulfate]. AB - We tested the laxative sodium picosulfate for mechanical bowel preparation in elective colorectal surgery. The quality of this preparation was assessed on a visual analog scale on 277 patients who were then followed prospectively for wound and intraabdominal infectious complications for 42 days. Picosulfate preparation resulted in a complication rate similar to whole gut irrigation but was more acceptable for the patients and the nurses. PMID- 1592646 TI - [Effect of continuous postoperative analgesia with peridural bupivacaine on intestinal motility following colorectal resection]. AB - In a prospective randomized trial the effects of continuous peridural analgesia on gastrointestinal motility and the postoperative course was studied in 48 consecutive patients with elective colorectal resections. 24 patients had peridural analgesia (PDA) with bupivacaine while 24 patients received intravenous analgesia (IVA) with pentazocine. With PDA the first passage of flatus and faeces was significantly accelerated. PDA was not associated with an increased rate of anastomotic breakdown and there were no respiratory complications in the PDA group. PMID- 1592647 TI - [Surgical therapy of diverticular disease at the Waid City Hospital, Zurich, 1980 1990]. AB - Our experience with 431 patients suffering from diverticular disease is presented. Indications for emergency (severe bleeding, bowel obstruction, sigmoid perforation with peritonitis) and elective surgery (recurrent attacks of diverticulitis or bleeding, painful or obstructing diverticular disease, fistula, impossibility to exclude a cancer) are given. Resection of the perforated sigmoid by the Hartmann procedure helps to reduce mortality markedly for diffuse purulent and fecal peritonitis. A resection with primary anastomosis can be performed with equal safety for a more localised peritonitis. Aggressive indication for elective surgery helps to lower mortality and morbidity in symptomatic diverticular disease. PMID- 1592648 TI - [Colostomy closure after Hartmann operation: functional results]. AB - The "Hartmann operation" for complication of acute diverticulitis or obstruction of the rectosigmoid is a safe procedure with few complications. However, it needs a second operation to reconstruct the continuity of the intestinal tract with more difficulties. The goal of our report is to show the 30-day morbidity and the late sequelae after colostomy closure with special concern to the late anorectal function. We analyzed 43 patients who underwent colostomy closure after Hartmann's procedure between 1985 and 1990. We controlled personally 35 patients after 32 months (range: 5-64 months) concerning their bowel habits, anal sphincter function (digital measure) and endoscopic anastomosis diameter. There were no deaths, but there was a 9% perioperative morbidity (1 anastomotic leak, 1 anastomotic bleeding and 2 wound infections). In the further course 2/35 patients were incontinent for gas and liquid stool. Further 3 patients lost water after coughing and had a poor sphincter rest tone. Our results demonstrates a low 30 day morbidity after reversal of Hartmann's procedure. It needs further investigation to show, if a damaged sphincter muscle or a lower rectum capacity could be responsible for these results. PMID- 1592649 TI - [The pattern of recurrence of T3 rectum cancer]. AB - Rectal carcinoma is one of the most common tumors of the GI-tract. At the time of initial treatment the majority of our patients had a stage T3 tumor. In order to contribute to the development of new guidelines for adjuvant therapies we analysed the patterns of recurrence in the patients operated with curative intention in our institution between 1981 and 1989. The pattern of recurrence shows that every fifth patient could benefit of a local measure to reduce local recurrence and that every second patient with positive nodal histopathology could benefit of a systemic adjuvant chemotherapy. PMID- 1592651 TI - [Experimental liver metastases of human colonic cancer: correlation with degree of differentiation and CEA production]. AB - The influence of cellular differentiation and CEA-production by colorectal tumor cells on experimental hepatic metastases was studied. Eight human colon cancer cell lines were injected into the spleen of athymic mice. The four poorly differentiated, non or low CEA producing cell lines were poorly metastatic to the liver. In contrast, the four well-differentiated cell lines which produce moderate to high levels of CEA were highly metastatic. We conclude in this animal model that poorly differentiated, non or low CEA producing colorectal cell lines have a lower metastatic potential compared to the well-differentiated, high CEA producing tumor cells. PMID- 1592650 TI - [Final evaluation of the randomized multicenter study SAKK 40/81: adjuvant portal chemotherapy of curatively resected colorectal cancer]. AB - Between 1981 and 1987, 533 patients from 9 institutions have been entered in a randomized trial to assess the value of adjuvant portal infusion (5-Fluorouracil, Mitomycin C) compared to radical surgery alone. Analysis of 469 evaluable patients at a median follow-up of 5.8 years revealed 110 recurrences in the control and 94 recurrences in the infusion group. Estimated 5-year disease-free survival was 52% and 61% respectively (hazard ratio 1:0.75; 95% confidence interval 0.57-0.99; p = 0.046). Overall survival was 59% in the control and 69 in the infusion group (p = 0.048). Adjuvant portal infusion did not influence the occurrence of liver metastases but reduced the overall recurrence rate. PMID- 1592652 TI - A dual level model for speciation by multiple pericentric inversions. AB - A considerable body of evidence suggests that the deleterious meiotic effects of pericentric inversions in F1 hybrids can be overcome by changes in chiasma location and various means of non-homologous pairing. Such overriding mechanisms may render pericentric inversions benign and increase the likelihood of their fixation in population isolates. It has been argued that overriding mechanisms of this type negate the involvement of pericentric inversions as reproductive isolating mechanisms in speciation. It is suggested, however, that the involvement of pericentric inversions in speciation should be considered on two levels. First, that by reducing meiotic effects in F1 hybrids, overriding mechanisms facilitate the fixation of pericentric inversions. Secondly, when contact hybridization occurs between the chromosomally derived and parental populations second-level effects may be encountered. That is, the recombinational effects of pericentric inversion differences on coadapted gene complexes (sensu Brncic, 1954, Shaw & Coates, 1983) enforce profound inviability barriers in F2 and backcross matings. In this way, multiple pericentric inversions may act as significant post-mating isolating mechanisms, whereas individual inversions with less significant second-level effects may not. PMID- 1592653 TI - Estimates and bounds on the rate and extent of allele frequency change. AB - Two approximations are provided to the frequency of an autosomal allele after any number of generations of selection and, conversely, to the number of generations required for any given frequency change. These estimates are accurate over a wide range of selection coefficients and initial conditions, and have the added advantage of providing strict upper and lower bounds to the true values under quite general conditions. The approach employed here, of finding exact solutions to approximating difference equations, could easily be applied to models with migration, mutation, etc. and, indeed, to any non-linear difference equation. In such applications, it offers several advantages over traditional methods from approximation theory. PMID- 1592654 TI - The human immunodeficiency virus (HIV) PMID- 1592655 TI - Homosexual and bisexual men infected with the human immunodeficiency virus (HIV) PMID- 1592656 TI - Regulation of the tension of human chorionic vasculature by histamine and prostaglandin F2 alpha. AB - The calcium dependence of potassium chloride-, prostaglandin F2 alpha (PGF2 alpha)-, and histamine-induced contractions of human chorionic vasculature segments was investigated. In physiologic buffer that contained 1.5 mM calcium chloride, 60 mM potassium chloride induced a rapid and sustained contraction of the vasculature. Potassium chloride-induced contractions were completely inhibited by the calcium channel blockers diltiazem and nifedipine or by excluding Ca2+ from the medium. Histamine (100 microM) induced a rapid increase in vascular tension in physiologic buffer which rapidly faded or desensitized after maximal tension was obtained. The maximal contractile responses to histamine were reduced approximately 50% by diltiazem and nifedipine in physiologic buffer or by suspension in calcium-free medium (OCaPB). Pretreatment of vessels with 20 mM caffeine in OCaPB completely abolished histamine-dependent contractile responses. Prostaglandin F2 alpha (100 nM)-induced increases in vascular tension developed slowly but remained maximal for at least 40 minutes. Contractile responses to PGF2 alpha were reduced 50% to 65% by diltiazem and nifedipine in physiologic buffer or by suspension in OCaPB. Caffeine pretreatment failed to alter the contractile response to PGF2 alpha in OCaPB. The differences in responsiveness of potassium chloride, histamine, and PGF2 alpha under the various conditions used suggest that these agents act by different mechanisms to elicit contractions in chorionic vessels. The potential roles of PGF2 alpha, histamine, and calcium channel blockers in modulating the fetoplacental circulation is discussed. PMID- 1592657 TI - The physical fitness of first-year osteopathic medical students. AB - The authors studied the physical fitness of first-year students attending an osteopathic medical college between 1981 and 1986. Overall, 319 (49.2%) of all students entering during this period participated in a comprehensive health and fitness assessment. The mean treadmill performance times for men and women were 20.4 minutes and 15.5 minutes, respectively, using a modified Balke protocol. Men and women were at the 72nd and 79th percentiles, respectively, for physical fitness. In multivariate regression models that adjusted for confounding variables, body fat percentage was a highly significant negative predictor of fitness in both men and women. Forced vital capacity was also a highly significant predictor in women. The results of the study suggest that the fitness of medical students can be improved by implementing health promotion measures that encourage regular physical activity and dietary modification. A greater emphasis on health promotion in the medical curriculum may help students to adopt more healthy behaviors and, in addition, encourage them to provide preventive medical counseling to their patients. PMID- 1592658 TI - Nociceptive considerations in treating with counterstrain. AB - The proprioceptive mechanistic model of somatic dysfunction proposed by Korr is accepted as the neurophysiologic basis of counterstrain by the developer of that manipulative technique. We suggest that the physician should also take into account the physical damage, if any, that the original trauma produced. We propose that with tissue injury, nociceptive reflexes could produce patterns of motion restriction opposite that predicted by a solely proprioceptive model. A nociceptive component is suggested as an explanation for the origin and maintenance of somatic dysfunction and its response to the counterstrain technique. In actuality, both proprioceptive and nociceptive responses may occur in dysfunctional states. Other physiologic responses also may be involved. These views are consistent with clinical experience. PMID- 1592659 TI - Acute severe asthma: Part 2. Current therapy. AB - Acute severe asthma is an extremely common and serious public health problem in the United States. Current optimum therapy of acute severe asthma includes supplemental oxygenation, nebulized beta-adrenergic receptor agonist therapy, and prompt use of glucocorticosteroids. In view of its low therapeutic index and the availability of more effective, less toxic agents, theophylline is no longer considered a first-line treatment. Ipratropium bromide combined with beta-agonist may augment bronchodilator responsiveness. PMID- 1592660 TI - Drug effects on laboratory values. AB - An abnormal laboratory value in any patient must be explained. Three factors may alter the laboratory test results: diet, disease, and drugs. Perusal of the Physicians' Desk Reference reveals the enormous influence drugs can have on the laboratory test results. The prescribing physician should be aware of any potential side effects of a drug he or she is prescribing and enlist the assistance of a qualified pathologist to decide what effects, if any, the medication has on observed anomalies. The clinical pathologist can also help the clinician to decide what further steps need to be taken to elucidate the problem. PMID- 1592661 TI - Clues for suspecting a patient is infected with the HIV. PMID- 1592662 TI - Case presentation as a teaching tool: making a good thing better. AB - Formal lectures have generally replaced case presentations as teaching tools for group learning in internship and residency programs. This article discusses two forms of case presentations--"traditional" and "chunked." Best used to convey medical information, the traditional approach proves less than optimal as a tool in teaching problem-solving skills. The "chunked" method, on the other hand, is an excellent format for formal small- and large-group instruction. An overview and suggested approach for each type is outlined herein. Properly used, each type can be a more efficient, effective tool than lectures when it comes to teaching medical problem-solving skills. PMID- 1592663 TI - National Cholesterol Education Program: highlights of the Report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. US Department of Health and Human Services, Public Health Service. National Institutes of Health, National Heart, Lung, and BloodInstitute. PMID- 1592664 TI - Changes in bit-mapped contingent negative variation (CNV) activity due to initial normal involutional processes of the human brain. AB - Bit-color mapped multicomponent CNV complexes and RTs to S2 evoked with a simple warned CNV/RT paradigm were recorded and measured in 20 selected right-handed very healthy volunteers (10 young adults and 10 presenile subjects, mean age 28.3 and 59.6, respectively). EEG and CNV components (post S1, N1, P2, P3; early CNV; N1200; late CNV; CNV resolution) were recorded from Fz, C3, Cz, C4, P3, Pz, and P4 referenced to linked mastoid electrodes. EOG, RT and stimuli were also recorded. The presenile group differed significantly from the younger group in the auditory post-S1 N1 and early (O-wave) and late (P-wave) CNV complex components. A progressive amplitude reduction limited to frontal leads between O wave and P-wave, the lowest point being reached in the P-wave, was characteristic in the presenile group. Moreover, presenile subjects showed relatively flat CNV waveshapes of low amplitude and, on the whole, performed a little less well than young ones. This finding suggests that the statistically significant changes in auditory post-S1 N1 and CNV activity recorded in our presenile subjects, without any appreciable deficits in behavioral or mental performance, could be alerting signs of early brain involutional processes related to minimal and subclinical decline in orienting, attentiveness and response preparation capabilities. If such is the case, and it could be confirmed in a larger sample of very healthy subjects, these age-related changes in the presenium might prove to be of considerable practical importance for clinical research. PMID- 1592665 TI - Two-dimensional manual tracking of periodic movements: event and time interval analyses. AB - Human visuo-motor functions were analysed by means of two-dimensional manual tracking tasks. A computer-based system for visual target generation, its movement control and real-time evaluation of the subjects' performance was developed. Various types of two-dimensional periodic target movements (over circular and square trajectories with different velocities) and various settings of tracking spot-joystick relation (normal and reversed direction) were used. Tracking success was expressed in terms of: (a) incidence of tracking errors; and (b) time spent within target. Results from the experiments performed with healthy non-trained subjects have demonstrated that tracking success is lower for a square target trajectory than for the circular one, and for higher target velocity than for the lower one. Reversed two-dimensional tracking was found to be very difficult. The results based upon the two criteria of tracking success (a,b) were different for the majority of tracking variants adopted. Quantitative and qualitative differences among subjects in tracking success were found. Two dimensional target movements were substantially more difficult than one dimensional ones with comparable parameters (analyzed in a previous paper). PMID- 1592666 TI - 42-channel potential map series to visual contrast and stereo stimuli: perceptual and cognitive event-related segments. AB - Event-related potential maps to perceptual (stimulus type) and cognitive (stimulus relevance) manipulations were studied in 12 healthy volunteers using 42 channel mapping. Perceptual manipulation used three types of visual stimuli: rectangles constituted by: (1) contrast; (2) different densities of monocular Dynamic Random Dots (Flat DRD); and (3) different binocular disparities of Dynamic Random Dots (Stereo DRD). Cognitive manipulation within each stimulus type consisted of presenting the rectangles horizontally and vertically, one of the two with a probability of 33%, and requesting the subjects to count and thus attend to the 'rare' rectangles. Spatial characteristics of the maps were analyzed; this allowed conclusions about the generating sources. The map series were adaptively segmented using the minima points of the grand mean Global Field Power curve. Segment strength (Global Field Power) and segment landscape (locations of extreme potentials) were assessed. Stimulus type had effects from 78 to 310 ms, stimulus relevance was effective from 210 to 1000 ms. In the 78-174 ms segment, Stereo DRD and Flat DRD stimuli produced similar map landscapes, while contrast stimuli produced different map landscapes. Attended and ignored stimuli produced contrary effects on landscapes at 210-310 ms as compared to those at 310-546 ms, indicative of different neural populations activated by attention processes during these late event-related potential segments. Interaction between perceptual and cognitive manipulation occurred at 210-310 ms when perceiving stereo stimuli and attending to relevant monocular visible stimuli produced similar map landscapes, suggesting a common brain resource during this segment for automatic figure perception and voluntary attention. The observed functional differences of the segments contribute to the identification of global functional microstates of brain electric activity. PMID- 1592667 TI - Influence of mood on visually evoked potentials: a prospective longitudinal study. AB - Anecdotal observations have suggested that individual differences in mood state could be one reason for the variability of visually evoked potentials (VEP). Therefore, we designed a longitudinal study, in which VEP amplitude was measured and psychological dimensions were assessed. All subjects completed a 'mood state questionnaire' before each session. The results from the VEP measurement and from the mood questionnaire varied widely between subjects. The intraindividual reproducibility, however, was high in 15 of 20 subjects, even over 4 weeks. In some cases we found intraindividual variability of VEP amplitude to be highly correlated with some factors derived from the mood state questionnaire. An overall analysis of covariance and variance (ANCOVA) showed a significant negative correlation between VEP amplitude and the mood factor 'Tiredness' and a significant positive correlation between VEP amplitude and 'Activity'. PMID- 1592668 TI - P300 in multiple sclerosis: a preliminary report. AB - The P300 component of the event-related brain potential (ERP) elicited with auditory stimuli and pattern-shift visual evoked potentials (VEPs) was obtained from 16 patients with multiple sclerosis (MS) and 16 matched control subjects. P300 latency was significantly longer and component amplitude relatively depressed in the MS patients compared to control subjects. The P100 potential of the VEP also was delayed for both full-field and half-field stimulus conditions in the patients compared to control subjects. The findings suggest that the P300 ERP may reflect the cognitive decline associated with MS. PMID- 1592669 TI - Test-retest reliability of inotropic and chronotropic measures of cardiac reactivity. AB - This study evaluated the retest reliability of a number of inotropic and chronotropic indexes of cardiovascular reactivity to mental arithmetic stress over a 1-week interval. Differential habituation effects of the dependent measures were also assessed. 15 male and 15 female undergraduate Ss were administered a mental arithmetic task (serial subtractions by 13 from a 4-digit number) for 1-min on two successive weeks while their electrocardiogram and impedance cardiogram were recorded. Dependent measures included HR, PEP, HI, SV and CO. Results indicate that all dependent measures were reliable. PMID- 1592670 TI - Differential responses to mental stress in high and low anxious normal humans assessed by frontal midline theta activity. AB - The distinct EEG theta rhythm from the frontal midline area observed during performance of mental tasks has been called Fm theta. In the present study, plasma catecholamine responses to mental stress were investigated using male students with (n = 12) and without (n = 12) Fm theta. The subjects were requested to complete the trait anxiety scale of STAI, and control blood samples were obtained. 65 min later, their EEGs were recorded during performance of an arithmetic addition task for 5 min. The state anxiety scores of STAI were obtained twice before and after the EEG recording. Blood samples were drawn three times during the state anxiety test and the EEG recording. The Fm theta appearance group showed low trait anxiety and a decrease of state anxiety after the mental task; however, the Fm theta non-appearance group exhibited high trait anxiety and no changes of state anxiety before and after the mental task. The concentrations of DA, HVA, NA and MHPG in the Fm theta appearance group showed lower levels at all times compared to those in the non-appearance group. In the Fm theta appearance group, an increase of DA turnover was observed by the addition of mental task. On the other hand, the Fm theta non-appearance group showed an increase of NA turnover. PMID- 1592671 TI - Off-line methods for detection and correction of EEG artefacts of various origin. AB - Conventional methods for the correction of the effects of blinking and eyeball movement artefacts in the EEG have been considered. The limitations of present methods are reviewed. Considering the brain as a volume conductor, the ways of revealing the ocular movement artefacts in the frontal EEG leads have been suggested. On the basis of the proposed criteria an optimal method of artefact correction in the frontal EEG leads have been developed. General principles in the developing the program for the correction of artefacts of different origin are set forth. PMID- 1592672 TI - Active and passive P3 latency and psychometric performance: influence of age and individual differences. AB - The relationship of P3 latency of the event-related potential (ERP) to psychometric performance was investigated in 41 subjects who ranged in age from 20 to 88 years. P3 responses were recorded from subjects using an auditory oddball paradigm with and without task-demands. Subjects also received psychometric tests of verbal performance, visuospatial performance, concentration, and immediate, recent and remote memory. Factor analysis was used to reduce the set of psychometric measures to four factors (Verbal learning, general intelligence, narrative recall/fluency, and concentration). Both passive and active P3 latency showed a linear increase with age. Age was inversely correlated with verbal learning performance. After accounting for the influence of age, passive P3 latency correlated with the psychometric factor associated with narrative recall and verbal fluency. Active P3 latency was correlated with factors reflecting general intelligence and concentration. These findings suggest that cognitive processing speed contributes to psychometric performance in adults. The psychological or biological basis for this relationship remains to be identified. PMID- 1592673 TI - Attentional influence on the P50 component of the auditory event-related brain potential. AB - To determine if attentional factors influence the suppression of the auditory P50 in a conditioning-testing paradigm, known as the 'sensory gating' effect, we tested 10 healthy young adults in four experimental conditions. The first condition was the traditional passive conditioning-testing paradigm in which a pair of identical auditory clicks is administered at an interstimulus interval fixed at 500 ms. The effect of interest is a reduction of P50 amplitude in response to the second stimulus. In the next condition, the second stimulus could be one of two possible frequencies and subjects were required to count one and to ignore the other. The third and fourth experimental conditions involved a motor response. In the third condition, subjects were required to make a unimanual button press to the occurrence of the second stimulus. In the fourth condition, subjects were required to discriminate among two possible second stimuli, and make a unimanual button press to the occurrence of the designated stimulus. Subjects also completed four matched blocks of single stimulus (i.e., unpaired) presentations to provide a baseline for assessing the effect of the warning stimulus on the evoked response. We found, in agreement with previous results, that passive exposure to the paired stimuli produced a suppression of P50 amplitude to the second stimulus. However, we also found that suppression of P50 amplitude was not evident when subjects selectively counted the designated stimuli, and was reduced in magnitude when a simple motor response was required and when a selective motor response was based on stimulus discrimination. In addition, we observed that the amplitude of the P50 was larger with unpaired single stimuli than it was either with the first or second stimulus of a pair, regardless of processing demands. Furthermore, variations in processing demands did not affect P50 amplitude when a single stimulus was presented. This pattern of results suggests that the 'sensory gating' effect is not a simple 'hard-wired' inhibitory phenomenon. Rather, it may be one manifestation of an attention regulation process that is activated by a warning stimulus and has either inhibitory or excitatory effects on neural transmission, determined by variations in processing demands. Presentation of a warning stimulus may have an additional, unselective suppressing effect, operating independently of this attention regulating process. PMID- 1592674 TI - The influence of age, work schedule and personality on morningness dimension. AB - The effects of age, work schedule and personality were investigated in 908 subjects by means of a reduced scale of Morningness-Eveningness-Questionnaire which contains questions regarding only the Morningness dimension. The results obtained for the work schedule and age maximized the inter-groups differences and the effects as compared to the original questionnaire. Extraversion correlated negatively with Morningness scores, while Sex and Neuroticism were not significantly related to this dimension. PMID- 1592675 TI - A83016F, a new member of the aurodox family. AB - A new member of the aurodox family of antibiotics, A83016F, has been isolated from an unidentified actionmycete designated A83016. The structure and relative stereochemistry of A83016F were elucidated by NMR examination of the parent compound and its diacetate derivative. A83016F exhibits only weak antimicrobial activity. PMID- 1592676 TI - Sch 42137, a novel antifungal antibiotic from an Actinoplanes sp. Fermentation, isolation, structure and biological properties. AB - A novel polycyclic xanthone, Sch 42137, related to the albofungin family of compounds was isolated from culture broth. Its structure was determined by detailed spectroscopic studies and comparison of circular dichroic studies to related compounds albofungin and simaomicin. Sch 42137 exhibited MIC values less than 0.125 micrograms/ml against yeasts and dermatophytes. Details are presented herein. PMID- 1592677 TI - 10'-Desmethoxystreptonigrin, a novel analog of streptonigrin. AB - 10'-Desmethoxystreptonigrin, a novel analog of streptonigrin produced by Streptomyces albus, was discovered in a screen for inhibitors of farnesylation of RAS p21 protein. The compound was isolated from the fermentation broth and its structure determined. It is markedly cytotoxic to several human tumor cell lines and also exhibits potent broad-spectrum antibacterial activity. PMID- 1592679 TI - Carbon catabolite regulation of gentamicin formation. AB - The effect of utilizable carbon sources on the production of gentamicin by Micromonospora purpurea has been studied. High D-glucose and D-xylose concentrations (40 mg/ml), exerted a strong and permanent negative action on antibiotic formation. On the other hand, similar concentrations of D-fructose, D mannose, maltose and starch caused no effect. The glucose action is seen only if added during the logarithmic growth phase; moreover, the sugar needs to be metabolized to show its negative effect. PMID- 1592678 TI - AB3217-A, a novel anti-mite substance produced by a strain of Streptomyces platensis. AB - AB3217-A, a novel anti-mite substance, was isolated from the fermentation broth of a streptomycete strain. The strain was isolated from a soil collected at Kita azumi, Nagano Prefecture, Japan, and identified as Streptomyces platensis AB3217. AB3217-A was purified by Amberlite IR120B, Diaion HP-20 and CM-Sephadex C-25 column chromatographies. The molecular formula was determined as C17H23NO7 by elemental analysis, MS and 13C NMR spectroscopy. The structure of AB3217-A was determined to be (1R,3S,4S,7R,8R,11R,12S,13R)-4,12,13-trihydroxy-8-(4-methoxy phenyl)-6-aza-2,9,14-trioxatricyclo-[9.2.1.0(3,7)]tetradecane by spectroscopic analysis and X-ray crystallographic analysis. The molecule of AB3217-A has unique structure that deacetylanisomycin and beta-D-xylofuranose linked through glycosidic bond and ether bond resulting in the formation of nine-membered ring. AB3217-A showed marked activity against the two spotted spider mite, Tetranychus urticae. PMID- 1592680 TI - New polyenic antibiotics active against gram-positive and gram-negative bacteria. IV. Structural elucidation of enacyloxin IIa. AB - The chemical structure of a unique polyenic antibiotic enacyloxin IIa (former name: fr. 2) produced by Frateuria (formerly Gluconobacter) sp. W-315 has been determined by extensive spectroscopic studies, in particular by NMR spectral analysis. It has a novel non-lactonic structure involving 3,4 dihydroxycyclohexanecarboxylic acid with a chlorine-containing polyenic and polyhydroxy acyl side chain attached as an ester to the 3-hydroxyl substituent of the acid. PMID- 1592681 TI - Studies on condensed-heterocyclic azolium cephalosporins. III. Synthesis and antibacterial activity of 7 beta-[2-(2-amino-5-substituted-thiazol-4-yl)-2 (Z) alkoxyiminoacetamido]-3-(condensed-heterocyclic azolium)methyl-3-cephem-4- carboxylates. AB - As a part of our research on the synthesis of cephalosporins bearing condensed heterocyclic azolium groups at the 3 position in the cephalosporin nucleus, we describe herein the synthesis of 7 beta-[2-(2-amino-5-halogeno-, methylthio-, methylsulfinyl-, methylsulfonyl- and sulfothiazol-4-yl)-2(Z) alkoxyiminoacetamido] cephalosporins and their antibacterial activity. Among the compounds prepared, 7 beta-[2-(2-amino-5-chlorothiazol-4-yl)-2(Z)- methoxyiminoacetamido]-3-(imidazo[1,5-a]-pyridinium-1-yl)methyl-3-cephem -4 carboxylate (14) showed good antibacterial activity against both Staphylococcus aureus including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, whereas the antibacterial activity against other Gram negative bacteria was a slightly lower than that of 7 beta-[2-(2-aminothiazol-4 yl)-2(Z)-methoxyiminoacetamido]-3-(im ida zo [1,2-a]pyridinium (I-1) and imidazo[1,5-a]pyridinium (I-4)-1-yl)methyl-3-cephem-4-carboxylates. PMID- 1592682 TI - New penem compounds with 5'-substituted pyrrolidinylthio group as a C-2 side chain; comparison of their biological properties with those of carbapenem compounds. AB - A series of new penem compounds with a C-2 side chain consisting of a pyrrolidin 3'-ylthio group substituted with various aminocarbonyl groups at the C-5' position have been prepared. Antibacterial activity, stability to renal dehydropeptidase-I and affinity to penicillin-binding proteins of these compounds were investigated and compared with the corresponding carbapenem compounds. PMID- 1592683 TI - RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. I. Antibacterial activity in vitro. AB - The aminothiazolyl-cephalosporin RU 29 246 is the active metabolite of the prodrug-pivaloyl-oxyethyl-ester HR 916. RU 29 246 in vitro activity includes a wide range of clinically relevant bacterial pathogens. Against methicillin sensitive Staphylococci RU 29 246 (MIC90 of 0.25 approximately 2 micrograms/ml) was clearly more active than cefaclor, cefuroxime, cefpodoxime, cefixime and ceftibuten, but slightly less active than cefdinir. RU 29 246 inhibited hemolytic Streptococci of the serogroups A, B, C and G as well as penicillin-sensitive Streptococcus pneumoniae at concentrations similar to cefdinir, cefpodoxime and cefuroxime (MIC90 less than or equal to 0.13 micrograms/ml), but less than the other oral cephalosporins investigated (cefixime, cefaclor and ceftibuten). MIC90s of RU 29 246 against Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Salmonella spp., Shigella spp., Proteus mirabilis and Haemophilus influenzae were less than or equal to 0.5 micrograms/ml. Only RU 29 246 and cefdinir demonstrated moderate activity against Acinetobacter baumannii (MIC90 greater than or equal to 4 micrograms/ml). Most strains of Pseudomonas spp., Serratia marcescens, Enterobacter spp., Hafnia alvei and Bacteroides spp. were resistant to RU 29 246. RU 29 246 killed Escherichia coli and Staphylococcus aureus at a rate of 99% to 99.9% at concentrations of two times MIC. The pH value of the medium (range 5.5 to 8.5) and the inoculum size (range 10(5) to 10(7) cfu/ml) had no or only low influence on the antibacterial activity of RU 29 246. RU 29 246 is a broad spectrum cephalosporin including in its activity both Gram positive and Gram-negative pathogens and therefore--depending on the bioavailability of its prodrug--looks promising as to its therapeutic perspective. PMID- 1592684 TI - RU 29 246, the active compound of the cephalosporin-prodrug-ester HR 916. II. Stability to beta-lactamases and affinity for penicillin-binding proteins. AB - The aminothiazolyl-cephalosporin RU 29 246, the active metabolite of the prodrug ester HR 916, is active against strains producing the widespread plasmid-encoded TEM-1, TEM-2 and SHV-1 beta-lactamases. Except for TEM-7 the activity of RU 29 246 against strains producing extended broad spectrum beta-lactamases (TEM-3, TEM 5, TEM-6, SHV-2, SHV-4, SHV-5, CMY-1, CTX-M), however, is low. Relative hydrolysis rates of RU 29 246 are comparable with those of cefpodoxime, the active metabolite of CS-807, and are extremely low for the TEM-1 and SHV-1 beta lactamases. The compound demonstrates remarkable inhibitory activity against the chromosomal beta-lactamase of Enterobacter cloacae P99. In the presence of 1.7 microM this enzyme loses 50% of its activity. At concentrations of 0.43, 0.003 and 0.01 micrograms/ml the compound binds preferentially to the penicillin binding protein (PBP) 3 of Escherichia coli K12, to the PBPs 2x and 3 of Streptococcus pneumoniae R6 and to PBP 1 of Staphylococcus aureus SG 511, respectively. PMID- 1592685 TI - Synthesis and antibacterial activities of new 3-phenoxymethylcephalosporins. AB - The synthesis and biological properties of new 3-phenoxymethylcephalosporins (1) are described. These compounds exhibited good antibacterial activity against Gram positive and Gram-negative bacteria. PMID- 1592686 TI - Conjugal transfer of imipenem resistance in Bacteroides fragilis. AB - Transfer of imipenem resistance in Bacteroides fragilis was studied. Clinical isolate B. fragilis 10-73 was highly resistant to imipenem. Imipenem resistance was transferred from 10-73 to B. fragilis strain TM4000 at a frequency of 10( 6)/input recipient by a filter mating technique. The resistance could also be retransferred. B. fragilis 10-73 and both primary and secondary transcipients produced an imipenem-hydrolyzing metallo-beta-lactamase. Acquisition of imipenem resistance correlated with the appearance of plasmid DNA with a size (ca. 13.6 kb) similar to that of the donor strain. TM4000 transformed by electroporation with purified DNA of the 13.6-kb plasmid pBFUK1 produced the metallo-beta lactamase and was resistant to imipenem. Transfer was resistant to DNase treatment and no transfer was seen with a sterile filtrate of the donor culture. It is suggested that gene transfer in B. fragilis has the properties of a conjugation system rather than those of transformation or transduction. PMID- 1592687 TI - Circumvention of multidrug resistance in human carcinoma KB cells by polyether antibiotics. AB - We examined the effect of various polyether antibiotics on colchicine resistance in multidrug-resistant KB-C4 cells which exhibit about 4,000-fold resistance to colchicine. As a result, 4 out of 14 polyether antibiotics were found to reverse colchicine resistance. Among them, laidlomycin was the most potent. It potentiated colchicine cytotoxicity on KB-C4 cells about 700-fold at 1 microgram/ml. Degree of potentiation was calculated by dividing of the IC50 value of colchicine in the absence of a polyether antibiotic by the IC50 value of colchicine in the presence of the polyether antibiotic. Monensin, dianemycin, and leuseramycin at 3 micrograms/ml also potentiated the cytotoxicity, about 100 fold. We previously reported that inostamycin is a potent chemosensitizer in KB C4 cells. Although lysocellin has a structure very similar to that of inostamycin, it didn't reverse colchicine resistance. It slightly increased [3H]vinblastine accumulation in KB-C4 cells and weakly inhibited the [3H]vinblastine binding to KB-C4 plasma membranes. PMID- 1592688 TI - Isolation and structures of two novel anti-mite substances, AB3217-B and C. PMID- 1592689 TI - New polyenic antibiotics active against gram-positive and gram-negative bacteria. VII. Isolation and structure of enacyloxin IVa, a possible biosynthetic intermediate of enacyloxin IIa. PMID- 1592690 TI - A83016A, a new kinamycin type antibiotic. PMID- 1592691 TI - A novel antibiotic, naphthopyranomycin. PMID- 1592692 TI - Dual-action penems. PMID- 1592693 TI - Synthetic cephalosporins. VIII. Synthesis and antibacterial activity of CP6232, a new anti-pseudomonal cephalosporin. PMID- 1592694 TI - Antibiotic uptake: unusual results for unusual molecules. PMID- 1592695 TI - When is penicillin monotherapy the antibiotic treatment of choice? PMID- 1592696 TI - Tetracyclines, molecular and clinical aspects. PMID- 1592697 TI - Permeability of the outer membrane of Moraxella catarrhalis for beta-lactam antibiotics. AB - The susceptibility of ten clinical isolates and a standard reference strain, ATCC25238, of Moraxella catarrhalis to 22 beta-lactam antibiotics was examined and compared with that of Escherichia coli strain B. All the strains of M. catarrhalis tested, especially the non beta-lactamase-producing strain ATCC25238, were more susceptible to a rang of structurally unrelated beta-lactam antibiotics, including small Mr carbapenems, than E. coli B. The permeability of the M. catarrhalis outer membrane to beta-lactam antibiotics was examined by the swelling technique with proteoliposomes reconstituted from outer membranes. The diffusion rate of beta-lactams through the liposome membrane was inversely related to their Mr, a relationship which might be expected for entry by diffusion through a porin. PMID- 1592698 TI - Resistance to a new catecholic cephem, BO-1341, in Pseudomonas aeruginosa PAO. AB - Two distinct types of mutant resistant to the catecholic cephem BO-1341 were isolated spontaneously from Pseudomonas aeruginosa PAO2146: (i) a mutant (CCB5 type) which produced beta-lactamase constitutively, and which appeared to result from a mutation in the regulatory gene (blaI at 41 min) controlling the structural gene (blaP at 25 min); (ii) a mutant (CCB7-type) with specific resistance to BO-1341. Induction of beta-lactamase production in strain CCB7 by BO-1341 was diminished markedly when compared with that in the parent strain. This was not the case for ceftazidime or cefoxitin, suggesting impaired uptake of BO-1341 as an explanation for the resistance. Electrophoretic analysis demonstrated increased production of a 55 kDa protein in the periplasmic space and a 84 kDa outer membrane protein. These data suggested that specific resistance to BO-1341 might involve quantitative alterations in the composition of the outer membrane and periplasmic proteins. PMID- 1592699 TI - Comparison of LY264826-gentamicin with vancomycin-gentamicin against enterococci from blood cultures. AB - The combination of the new glycopeptide LY264826 and gentamicin was compared with the combination of vancomycin and gentamicin against 30 strains of enterococci, comprising 20 strains of Enterococcus faecalis, five strains of Enterococcus faecium and five strains of Enterococcus avium, isolated from blood cultures. LY264826 plus gentamicin was synergic against E. faecalis and E. faecium, but not against E. avium. PMID- 1592700 TI - The inhibitory effect of ciprofloxacin on proliferation of a murine bladder carcinoma cell line. AB - Ciprofloxacin was tested for its effect on proliferation of a bladder carcinoma cell line, Jurkat T-cell leukaemia cell line and a normal human foreskin derived from a fibroblast cell line. Cell proliferation was measured by MTT tetrazolium salt colorimetric assay. Proliferation of bladder carcinoma cells was inhibited by ciprofloxacin in a dose and time dependent fashion. Initial inhibition was observed at a concentration of 25 mg/L (approximately 35% inhibition; P greater than 0.01) while 250 mg/L of ciprofloxacin, a concentration achievable in urine following conventional oral treatment, exerted a lytic effect on these cells. A maximum suppressive effect on cell proliferation was reached within the first 24 h of ciprofloxacin addition to cell cultures. The rate of reversal of the inhibition of proliferation was dependent on the initial drug concentration. Exposure of bladder carcinoma cell cultures to 250 mg/L ciprofloxacin resulted in irreversible inhibition of proliferation. Similar results were obtained for the fibroblast cell line and Jurkat T-cell line. The latter being slightly more sensitive towards ciprofloxacin treatment in vitro. PMID- 1592701 TI - The effect of amoxycillin on vaginal colonization resistance and normal vaginal flora in monkeys. AB - Previous studies have shown that vaginal colonization resistance in monkeys can be eliminated by amoxycillin and restored by flushing vaginal flora from a healthy monkey into the vagina of a monkey colonized with Escherichia coli. The hypothesis that the effect of amoxycillin resulted from elimination of parts of the normal flora was tested in the present study. Nine monkeys were flushed vaginally with amoxycillin daily for six days. The number of anaerobic bacteria decreased during amoxycillin administration, as did the number of species isolated. The most obvious effects were observed among the genera Bacteroides and Peptostreptococcus, while Lactobacillus spp. were less affected. Restoration of the flora after amoxycillin administration was slow in most of the monkeys. During amoxycillin administration, all monkeys became colonized spontaneously with E. coli. This was not, however, associated with increased adherence in vitro. The colonization persisted throughout the study period (29 days). It was concluded that amoxycillin disturbs vaginal colonization resistance by eliminating at least part of the normal vaginal flora, thereby promoting periurethral colonization with enterobacteria. PMID- 1592702 TI - The frequency of extended-spectrum beta-lactamases in isolates of Klebsiella pneumoniae. PMID- 1592703 TI - Bioassay for glycopeptides. PMID- 1592704 TI - Resistance of Streptococcus pneumoniae to erythromycin in adults and children. PMID- 1592705 TI - The emergence of highly fluoroquinolone-resistant Escherichia coli in community acquired urinary tract infections. PMID- 1592706 TI - Cefuroxime axetil in the sick elderly patient. PMID- 1592707 TI - Recurrent Listeria monocytogenes meningitis treated with intraventricular vancomycin. PMID- 1592708 TI - Load compensation and respiratory muscle function during sleep. AB - The sleeping state places unique demands on the ventilatory control system. The sleep-induced increase in airway resistance, the loss of consciousness, and the need to maintain the sleeping state without frequent arousals require the presence of complex compensatory mechanisms. The increase in upper airway resistance during sleep represents the major effect of sleep on ventilatory control. This occurs because of a loss of muscle activity, which narrows the airway and also makes it more susceptible to collapse in response to the intraluminal pressure generated by other inspiratory muscles. The magnitude and timing of the drive to upper airway vs. other inspiratory pump muscles determine the level of resistance and can lead to inspiratory flow limitation and complete upper airway occlusion. The fall in ventilation with this mechanical load is not prevented, as it is in the awake state, because of the absence of immediate compensatory responses during sleep. However, during sleep, compensatory mechanisms are activated that tend to return ventilation toward control levels if the load is maintained. Upper airway protective reflexes, intrinsic properties of the chest wall, muscle length-compensating reflexes, and most importantly chemoresponsiveness of both upper airway and inspiratory pump muscles are all present during sleep to minimize the adverse effect of loading on ventilation. In non-rapid-eye-movement sleep, the high mechanical impedance combined with incomplete load compensation causes an increase in arterial PCO2 and augmented respiratory muscle activity. Phasic rapid-eye-movement sleep, however, interferes further with effective load compensation, primarily by its selective inhibitory effects on the phasic activation of postural muscles of the chest wall. The level and pattern of ventilation during sleep in health and disease states represent a compromise toward the ideal goal, which is to achieve maximum load compensation and meet the demand for chemical homeostasis while maintaining sleep state. PMID- 1592709 TI - Air embolism-induced lung injury in isolated rat lungs. AB - Pulmonary air embolism causes physical obstruction of microvasculature and leads to permeability changes, release of mediators, and injury to lung tissue. In this study we employed an isolated perfused rat lung model to investigate the primary and secondary effects produced by infusion of air into the pulmonary artery. Infusion of various doses of air (0.10-0.25 ml) over a 1-min period produced a dose-dependent increase in pulmonary arterial pressure and lung weight gain. In contrast, when a constant air dose was administered over various periods of time (0.25 ml over 0.5-8.0 min), the pulmonary arterial pressure rose to the same extent regardless of the infusion rate, whereas the lung weight gain increased proportionately with the rate of infusion. Total vascular resistance rose from 1.41 +/- 0.04 to 5.04 +/- 0.09 mmHg.ml-1.min in rats given 0.25 ml air over 1 min (n = 14, P less than 0.001), with greater than or equal to 90% of this increase occurring in the arterial segments. Both thromboxane B2 and endothelin concentrations also increased in the perfusate, suggesting their involvement in this increased resistance. Furthermore the pulmonary filtration coefficient increased from 0.21 +/- 0.05 to 1.28 +/- 0.26 g.min-1.cmH2O-1.100 g (n = 8, P less than 0.001), and the protein concentration in lung lavage fluid also rose, indicating lung injury. Leukocyte counts in the perfusate were unaffected by embolization, but chemiluminescent activity was increased, indicating a possible role for activated leukocytes in lung injury induced by air emboli.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592710 TI - Nasal flow-resistive responses to challenge with cold dry air. AB - Recent studies have suggested that the inhalation of cold air through the nose is associated with the subsequent release of mediators of immediate hypersensitivity. To determine if mucosal surface heat and water loss influence the nasal functional response to cold air, we measured nasal resistance by posterior rhinomanometry before and 1, 5, and 10 min after a 4-min period of isocapnic hyperventilation (30 l/min) through the nose in nine healthy subjects (5 males, 4 females; aged 25-39 yr) while they inhaled air at 0 degrees C. During the challenge period, the subjects breathed either in and out of the nose or in through the nose and out through the mouth. No changes in nasal resistance developed when subjects breathed exclusively through the nose; however, when subjects breathed in through the nose and out through the mouth, nasal resistance was increased 200% at 1 min (P less than 0.01) after the challenge and returned to baseline values by 10 min after cessation of the challenge. These data indicate that nasal functional responses to cold dry air are dependent on the pattern of the ventilatory challenge. If the heat given up from the nasal mucosa to the incoming air is not recovered during expiration (as is the case with inspiration through the nose and expiration through the mouth), nasal obstruction will occur. Hyperpnea of cold air, per se, does not influence nasal resistance. PMID- 1592711 TI - Systemic responses to carotid occlusion in the anesthetized rat. AB - We evaluated the effects of four standard anesthetization regimens on the systemic cardiovascular responses to bilateral common carotid artery occlusion in 28 adult male rats. Rats were randomly assigned to anesthesia groups: thiopental sodium (PT; 100 mg/kg ip), alpha-chloralose (CH; 100 mg/kg iv), ketamine hydrochloride plus acepromazine (KA; 135 mg/kg and 1.5 mg/kg sc), and pentobarbital sodium (PB; 50 mg/kg ip). PT and PB animals had similar baseline heart rates (HR; 333 and 345 beats/min, respectively) and arterial pressures (MAP; 126 and 118 mmHg, respectively), whereas both were lower in CH and KA (314 and 288 beats/min, 92 and 85 mmHg). During bilateral carotid occlusion, PT demonstrated the largest change in MAP (dMAP; +27 mmHg) but the smallest change in HR (dHR; +8 beats/min). CH and PB demonstrated similar dHR (+24 and +16 beats/min) and dMAP (+20 and +19 mmHg). KA demonstrated a significant dHR (+14 beats/min), but the average dMAP was not statistically significant (+3 mmHg). Therefore, carotid occlusion in rats anesthetized with PT, PB, or CH consistently elicits a systemic arterial pressor response comparable with that reported for conscious animals. When the magnitude and stability of baseline HR and MAP are also considered, PT and PB anesthetization seem to be the most reliable for evaluation of the carotid occlusion pressor response in rats. PMID- 1592712 TI - Maturation of steady-state CO2 sensitivity in vagotomized anesthetized lambs. AB - The maturation of the respiratory sensitivity to CO2 was studied in three groups of anesthetized (ketamine, acepromazine) lambs 2-3, 14-16, and 21-22 days old. The lambs were tracheostomized, vagotomized, paralyzed, and ventilated with 100% O2. Phrenic nerve activity served as the measure of respiration. The lambs were hyperventilated to apneic threshold, and end-tidal PCO2 was raised in 0.5% steps for 5-7 min each to a maximum 7-8% and then decreased in similar steps to apneic threshold. The sinus nerves were cut, and the CO2 test procedure was repeated. Phrenic activity during the last 2 min of every step change was analyzed. The CO2 sensitivity before and after sinus nerve section was determined as change in percent minute phrenic output per Torr change in arterial PCO2 from apneic threshold. Mean apneic thresholds (arterial PCO2) were not significantly different among the groups: 34.8 +/- 2.08, 32.7 +/- 2.08, and 34.7 +/- 2.25 (SE) Torr for 2- to 3-, 14- to 16-, and 21- to 22-day-old lambs, respectively. After sinus denervation, apneic thresholds were raised in all groups [39.9 +/- 2.08, 40.9 +/- 2.08, and 45.3 +/- 2.25 (SE) Torr, respectively] but were not different from each other. CO2 response slopes did not change with age before or after sinus nerve section. We conclude that carotid bodies contribute to the CO2 response during hyperoxia by affecting the apneic threshold but do not affect the steady-state CO2 sensitivity and the central chemoreceptors are functionally mature shortly after birth. PMID- 1592714 TI - Structural change of the thorax in chronic obstructive pulmonary disease. AB - This study examines structural changes of the thorax in hyperinflated subjects with chronic obstructive pulmonary disease (COPD). Age-matched normal subjects were used for comparison. Thoracic dimensions were determined using anteroposterior and lateral chest radiographs performed at total lung capacity, functional residual capacity, and residual volume. Rib cage dimensions (lateral diameter, rib angle, anteroposterior diameter) and diaphragm position were determined at each lung volume. There were no significant differences in rib cage dimension between the COPD and normal subjects for all lung volumes. In contrast, the diaphragm was significantly lower in the COPD subjects. The change of rib cage dimensions in the COPD subjects (for a similar volume change) was not different from that in normal subjects, whereas the change of diaphragm position in the COPD subjects (for a similar volume change) was reduced. In conclusion, the primary structural change of the thorax in COPD with chronic hyperinflation is confined to the diaphragm, with no appreciable structural change in the rib cage. PMID- 1592713 TI - Effect of hyaluronidase on interstitial cuff and pressure response in liquid inflated rabbit lung. AB - The sequential pattern of perivascular interstitial cuff growth was studied in liquid-inflated rabbit lungs. Degassed isolated lungs were immersed in a saline bath and inflated to 5 cmH2O transpulmonary pressure with a 3% albumin solution or 3% albumin solution containing hyaluronidase. After inflation times varying between 1 and 7 h, the lungs were frozen in liquid N2. From blocks cut from the frozen lungs, interstitial cuff cross-sectional area was measured as a function of vessel size. No cuffs were observed around vessels less than 0.1 mm diam. At all inflation times, only approximately 50% of vessels less than 0.5 mm diam had cuffs, whereas virtually all vessels greater than 0.5 mm diam had cuffs. Cuff-to vessel area ratio increased with inflation time, reaching a maximum of 1.0-1.4 by 5 h. The time constant of cuff growth was 1 h for the albumin-inflated lungs and was independent of vessel size. The time constant was reduced by 60% in the hyaluronidase-inflated lungs. The time constant for the response in perivascular interstitial pressure measured by micropuncture near the lung hilum was 2.5 h for albumin-inflated lungs and 1.2 h for hyaluronidase-inflated lungs. Electrical analog models were used to fit the experimental data of cuff growth and to determine interstitial liquid resistance. Interstitial resistance for the albumin inflated rabbit lungs was 2- and 24-fold greater than values estimated previously for sheep and dog lungs, respectively. PMID- 1592715 TI - Effects of arginine/lysine supplementation and resistance training on glucose tolerance. AB - The purpose of this study was to evaluate and compare the effects of arginine/lysine supplementation (AL) and resistance training (RT) on changes in glucose tolerance and to determine whether alterations were associated with changes in selected hormonal parameters. The study involved 30 physically active college males, ages 20-30 yr, randomly assigned to one of four groups: placebo/control (P/C, n = 7), P/RT (n = 8), AL/C (n = 7), or AL/RT (n = 8). An AL supplement at a daily morning dose of 132 mg/kg fat-free body mass or placebo was administered orally to controls and training groups. During the 10-wk program, exercise subjects participated in a progressive resistance training program stressing all major muscle groups. Three-hour oral glucose tolerance (OGT) tests were performed on each subject before and after the 10-wk intervention to evaluate resting levels and responses of glucose, insulin, and glucagon. OGT parameters did not significantly change after intervention. It was concluded that neither AL supplementation nor RT had a significant effect on OGT. PMID- 1592716 TI - Changes in plasma and erythrocyte K+ during hypercapnia and different grades of exercise in trout. AB - Trout were exposed to hypercapnia, two levels of aerobic exercise, or three successive periods of supramaximal exercise to evaluate the effects on erythrocyte and plasma K+. During aerobic exercise, plasma K+ increased slightly with the intensity of work, while no change was found in the erythrocyte K+ content. In contrast, both hypercapnia and supramaximal exercise induced a net erythrocyte K+ uptake. This uptake changed to a net loss of K+ as arterial pH and hemoglobin-bound oxygen saturation returned to control values during recovery. The maximal rates of net K+ uptake found during hypercapnia and supramaximal exercise corresponded to 195 and 350 mumol.kg fish-1.h-1, respectively, and the maximal rates of net K+ loss found during recovery corresponded in both cases to approximately 130 mumol.kg fish-1.h-1. Hypercapnia had only a minor effect on plasma K+, but return to normocapnic conditions induced a 0.8 mM rise in plasma K+. Of this increase, approximately 70% could be accounted for by the simultaneous net release of erythrocyte K+. Each period of supramaximal exercise induced an elevated plasma K+ level, resulting in accumulation of plasma K+ despite slight decreases in plasma K+ in between the exercise periods. At the same time the net erythrocyte K+ uptake caused an estimated reduction in plasma K+ of 1.5 mM. It is concluded that both hypercapnia and supramaximal exercise cause profound net changes in the erythrocyte K+ content with significant effects on plasma K+. PMID- 1592717 TI - In vitro effects of pH and hemoglobin-oxygen saturation on plasma and erythrocyte K+ levels in blood from trout. AB - Plasma and erythrocyte K+ were monitored during storage and tonometry of blood samples taken from resting rainbow trout, Oncorhynchus mykiss. During storage of arterial blood samples, plasma K+ concentration increased by 38% in 12 min. During extended tonometry of blood with a pH near 7.9 and full hemoglobin-bound oxygen (HbO2) saturation the erythrocytes showed a net loss of K+. Plasma K+ concentration increased from 2.9 mM to a near steady-state value of 5.6 mM. When tonometered at a pH near 7.2 and a HbO2 saturation at approximately 4% the erythrocytes took up K+, leading to a dramatic reduction in plasma K+ concentration to 0.2 mM. This net uptake was stimulated by isoprenaline and was inhibited by ouabain. It is concluded that net erythrocyte K+ uptake and loss can be induced in trout by changes in blood pH or HbO2 saturation in vitro. PMID- 1592718 TI - Acute and habitual caffeine ingestion and metabolic responses to steady-state exercise. AB - This study compared the exercise catecholamine and metabolic responses to a caffeine challenge in trained subjects before and after a 6-wk period of increased caffeine ingestion. Trained subjects (n = 6) were challenged with 500 mg of caffeine followed by prolonged exercise before and after 6 wk of increased caffeine ingestion (500 mg ingested before each daily run). A control group (n = 6) of trained subjects followed the same protocol except for caffeine ingestion. Acute caffeine ingestion resulted in increased plasma epinephrine and decreased respiratory exchange ratio (RER) during exercise. After 6 wk of caffeine supplementation, the epinephrine response to exercise or caffeine plus exercise was decreased, although the latter still resulted in a lower RER value compared with exercise without caffeine ingestion. Activity of key metabolic enzymes (hexokinase, citrate synthase, phosphorylase, and 3-hydroxyacyl-coenzyme A dehydrogenase) from biopsies of the gastrocnemius showed no response to 6 wk of this increased adrenergic receptor stimulation and, on the basis of the lower RER, enhanced fat metabolism. This study suggests that caffeine ingestion by trained subjects causes increases in plasma epinephrine and reduces the RER during exercise. However, habitual stimulation results in a general dampening of the epinephrine response to caffeine or exercise. There was no indication that increased adrenergic stimulation and fat oxidation caused any adaptation in the activity of metabolic enzymes. PMID- 1592719 TI - Effect of hindlimb unweighting on anaerobic metabolism in rat skeletal muscle. AB - Female Sprague-Dawley rats (250 g) were hindlimb suspended for 14 days, and the effects of hindlimb unweighting (HU) on skeletal muscle anaerobic metabolism were investigated and compared with nonsuspended controls (C). Soleus (SOL), plantaris (PL), and red and white portions of the gastrocnemius (RG, WG) were sampled from resting and stimulated limbs. Muscle atrophy after HU was 46% in SOL, 22% in PL, and 24% in the gastrocnemius compared with nonsuspended C animals. The muscles innervated by the sciatic nerve were stimulated to contract with an occluded circulation for 60 s with trains of supramaximal impulses (100 ms, 80 Hz) at a train rate of 1.0 Hz. Peak tension development by the gastrocnemius-PL-SOL muscle group was similar in HU and C animals (13.0 +/- 1.2, 12.2 +/- 0.8 N/g wet muscle). Occlusion of the circulation before stimulation created a predominantly anaerobic environment, and in situ glycogenolysis and glycolysis were estimated from accumulations of glycolytic intermediates. Total glycogenolysis and glycolysis were higher in the RG muscle of HU animals (74.6 +/- 3.3, 58.1 +/- 1.1) relative to C (57.1 +/- 4.6, 46.1 +/- 2.9 mumol glucosyl units/g dry muscle). Consequently, total anaerobic ATP production was also increased (HU, 251.3 +/- 1.1; C, 204.6 +/- 8.9 mumol ATP/g dry muscle). Total ATP production, glycogenolysis, and glycolysis were unaffected by HU in SOL, PL, and WG muscles. The enhanced glycolytic activity in RG after HU may be attributed to a shift in the metabolic profile from oxidative to glycolytic in the fast oxidative glycolytic fiber population. PMID- 1592720 TI - Rate of formation of carboxyhemoglobin in exercising humans exposed to carbon monoxide. AB - The purpose of this study was to test the CFK equation for its prediction of the rate of formation of carboxyhemoglobin (HbCO) in exercising humans by use of measured values of the respiratory variables and to characterize the rate of appearance of HbCO with frequent blood sampling. Ten nonsmoking male subjects were exposed to carbon monoxide (CO) on two separate occasions distinguished by the level of activity. Steady-state exercise was conducted on a cycle ergometer at either a low (approximately 45 W) or moderate (approximately 90 W) power output. Each experiment began with an exposure of 3,000 ppm CO for 3 min during a rest period followed by three intermittent exposures ranging from 3,000 ppm CO for 1 min at low exercise to 667 ppm CO for 3 min at moderate exercise. Increases in HbCO were normalized against predicted values to account for individual differences in the variables that govern CO uptake. No difference in the normalized uptake of CO was found between the low- and moderate-exercise trials. However, the CFK equation underpredicted the increase in HbCO for the exposures at rest and the first exposure at exercise, whereas it overpredicted for the latter two exposures at exercise. The net increase in HbCO after all exposures (approximately 10% HbCO) deviated by less than 1% HbCO between the measured and predicted values. The rate of appearance of HbCO fits a sigmoidal shape with considerable overshoot at the end of exposure. This can be explained by delays in the delivery of CO to the blood sampling point (dorsal hand vein) and by a relatively small blood circulation time compared with other regions of the body. A simple circulation model is used to demonstrate the overshoot phenomenon. PMID- 1592721 TI - Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation. AB - To determine if prophylactic corticosteroids would prevent acute lung injury caused by hyperoxia and barotrauma, 29 piglets (1.2 +/- 0.3 kg, 1-2 days of age) were studied. Ten piglets were hyperventilated [arterial PCO2 (PaCO2) 15-20 Torr] with 100% O2 for 48 h and compared with 10 piglets treated with the identical management but given 0.7 mg/kg of dexamethasone at time 0 and every 12 h for the 48-h study. Six piglets were normally ventilated (PaCO2 40-45 Torr) for 48 h with 21% O2 as an additional control group. Pulmonary function and tracheal aspirates were examined at time 0 and every 24 h. Bronchoalveolar lavage was performed for surfactant analyses at the conclusion of the study. In animals treated with hyperoxia and hyperventilation, lung compliance decreased 32% and tracheal aspirate polymorphonuclear leukocyte (PMN) chemotactic activity increased by 51%, cell counts by 204%, number of PMNs by 277%, elastase activity by 111%, and albumin concentration by 328% over 48 h (P less than 0.05). In contrast, dexamethasone-treated piglets had increases in only tracheal aspirate albumin concentration (206%) over the 48-h study. All cellular and biochemical variables were lower in dexamethasone-treated compared with hyperoxic hyperventilated piglets. Room air normal ventilation controls had only a 108% increase in tracheal aspirate albumin concentration noted. Despite quantitative differences in surfactant among the three groups, activity was unaffected. Results indicate that hyperoxia and hyperventilation for 48 h causes significant inflammatory changes and acute lung injury and that prophylactic high-dose dexamethasone significantly ameliorates this lung damage. PMID- 1592722 TI - Tolerance and upregulation of acetylcholine receptors follow chronic infusion of d-tubocurarine. AB - The hypothesis that chronic competitive antagonism of nicotinic acetylcholine receptors (nAChR), even in the absence of immobilization or paralysis, induces proliferation of the receptor and tolerance to the competitive antagonist was tested. Chronic antagonism of the nAChR was achieved in rats by an infusion of d tubocurarine (dTC) via subcutaneously placed osmotic pumps. After 2 wk of dTC or saline, the neuromuscular pharmacodynamics and nAChR number were examined. No differences in weight gain or mobility were observed between groups. Chronic dTC infusion at 2 wk resulted in a baseline concentration of 0.41 +/- 0.07 (SE) micrograms/ml, which, if achieved acutely, would cause a depression of the twitch tension to 60% of control twitch height. Moreover the experimental group was able to develop a baseline twitch tension of 50 g, similar to that of controls. Despite the baseline dTC concentration in the experimental group, the effective doses of dTC for twitch depression were similar to those of controls. The plasma dTC concentration required for steady-state twitch inhibition was significantly (P less than 0.05) higher in the experimental group (0.83 +/- 0.04 vs. 0.50 +/- 0.15 micrograms/ml) as were the extrajunctional nAChR (19.76 +/- 1.77 vs. 13.37 +/- 1.82 fmol/mg protein). The diaphragmatic nAChR were unaltered. This study confirms that chronic doses of dTC cause tolerance to its effects and proliferation of nAChR even in the absence of immobilization. The absence of nAChR changes in the diaphragm may be due to the higher margin of safety of the diaphragm for muscle relaxants than for peripheral muscles. Intensive Care Unit patients receiving chronic infusions of dTC to facilitate mechanical ventilation will require increased doses with time. PMID- 1592723 TI - Lung tissue resistance during contractile stimulation: structural damping decomposition. AB - Research in the mechanics of soft tissue, and lung tissue in particular, has emphasized that dissipative processes depend predominantly on the viscous stress. A corollary is that dissipative losses may be expressed as a tissue viscous resistance, (Rti). An alternative approach is offered by the structural damping hypothesis, which holds that dissipative processes within soft tissue depend directly more on the elastic stress than on the viscous stress. This implies that dissipative and elastic processes within lung tissues are coupled at a fundamental level. We induced alterations of Rti by exposing canines to aerosols of the constrictors prostaglandin F2 alpha, histamine, and methacholine and by changing volume history. Using the structural damping paradigm, we could separate those alterations in Rti into the product of two distinct contributions: change in the coefficient of coupling of dissipation to elastance (eta) and change in the elastance itself (Edyn). Response of Edyn accounted for most of the response of resistance associated with contractile stimulation; it accounted for almost all the response associated with differences in volume history. The eta changed appreciably with constriction but accounted for little of the response of Rti with volume history. According to the structural damping hypothesis, induced changes in eta with constriction must reflect changes in the kinetics of the stress-bearing process, i.e., differences in cross-bridge kinetics within the target contractile cell and/or differences in the influence of the target cell on other stress-bearing systems. We conclude that, regardless of underlying processes, the structural damping analysis demonstrates a fundamental phenomenological simplification: when Edyn responds, Rti is obligated to respond to a similar degree. PMID- 1592724 TI - Analysis of human chest wall motion using a two-compartment rib cage model. AB - We present a model of chest wall mechanics that extends the model described previously by Macklem et al. (J. Appl. Physiol. 55: 547-557, 1983) and incorporates a two-compartment rib cage. We divide the rib cage into that apposed to the lung (RCpul) and that apposed to the diaphragm (RCab). We apply this model to determine rib cage distortability, the mechanical coupling between RCpul and RCab, the contribution of the rib cage muscles to the pressure change during spontaneous inspiration (Prcm), and the insertional component of transdiaphragmatic pressure in humans. We define distortability as the relationship between distortion and transdiaphragmatic pressure (Pdi) and mechanical coupling as the relationship between rib cage distortion and the pressure acting to restore the rib cage to its relaxed configuration (Plink), as assessed during bilateral transcutaneous phrenic nerve stimulation. Prcm was calculated at end inspiration as the component of the pressure displacing RCpul not accounted for by Plink or pleural pressure. Prcm and Plink were approximately equal during quiet breathing, contributing 3.7 and 3.3 cmH2O on average during breaths associated with a change in Pdi of 3.9 cmH2O. The insertional component of Pdi was measured as the pressure acting on RCab not accounted for by the change in abdominal pressure during an inspiration without rib cage distortion and was 40 +/- 12% (SD) of total Pdi. We conclude that there is substantial resistance of the human rib cage to distortion, that, along with rib cage muscles, contributes importantly to the fall in pleural pressure over the costal surface of the lung. PMID- 1592725 TI - Microscopic vs. macroscopic deformation of the pulmonary alveolar duct. AB - The stretch of the perimeters of alveolar ducts was measured at the surface of saline-filled specimens of human and dog lung parenchyma that were stretched biaxially. The microscopic stretch of these ducts was measured at several levels of isotropic biaxial macroscopic stretch of the parenchyma with stretch ratio (lambda x = lambda y) in the range of 1.20-1.40, which roughly corresponds to tidal breathing in humans and dogs. Alveolar walls were found to be load-carrying elements in the saline-filled lung, as seen by their straightness at all levels of stretch. Quantitatively, let l, A, L, and S denote, respectively, the duct perimeter length and area and the parenchymal target perimeter and area in the deformed state and lo, Ao, Lo, and So the corresponding variables in the undeformed state. The microscopic stretch ratio of the ducts (l/lo) was found to be approximately 4% larger than the macroscopic stretch ratio (L/Lo) in human lung and approximately 10% larger in dog lung. The microscopic area ratio of the ducts (A/Ao) was found to be approximately 10% larger than the macroscopic area ratio (S/So) in human lung and approximately 22% larger in dog lung. Ducts within human parenchyma were seen to be about twice as stiff as ducts within dog parenchyma over the range of macroscopic stretch studied. This correlates with the volume fractions of collagen and elastin being higher in the human lung than in dog lung. The observed nonuniformity in strain field at the microstructural level suggests the need to include a force balance between alveolar ducts and septal walls when modeling the mechanics of saline-filled parenchyma. PMID- 1592726 TI - Vagal contributions to respiratory muscle activity during eupnea in the awake dog. AB - We examined the effects of reversible vagal cooling on respiratory muscle activities in awake chronically instrumented tracheotomized dogs. We specifically analyzed electromyographic (EMG) activity and its ventilatory correlates, end expiratory lung volume (EELV) and diaphragmatic resting length via sonomicrometry. Elimination of phasic and tonic mechanoreceptor activity by vagal cooling doubled the EMG activity of the costal, crural, and parasternal muscles, with activation occurring sooner relative to the onset of inspiratory flow. Diaphragmatic postinspiration inspiratory activity in the intact dog coincided with a brief mechanical shortening of the diaphragm during early expiration; vagal blockade removed both the electrical activity and the mechanical shortening. Vagal blockade also doubled the EMG activity of a rib cage expiratory muscle, the triangularis sterni, but reduced that of an abdominal expiratory muscle, the transversus abdominis. Within-breath electrical activity of both muscles occurred sooner relative to the onset of expiratory flow during vagal blockade. Vagal cooling was also associated with a 12% increase in EELV and a 5% decrease in end-expiratory resting length of the diaphragm. We conclude that vagal input significantly modulates inspiratory and expiratory muscle activities, which help regulate EELV efficiently and optimize diaphragmatic length during eupneic breathing in the awake dog. PMID- 1592727 TI - Vagal modulation of respiratory muscle activity in awake dogs during exercise and hypercapnia. AB - Using chronically instrumented awake tracheotomized dogs, we examined the contributions of vagal feedback to respiratory muscle activities, both electrical and mechanical, during normoxic hypercapnia (inspired CO2 fraction = 0.03, 0.04, 0.05, and 0.06) and during mild treadmill exercise (3, 4.3, and 6.4 km/h). Cooling exteriorized vagal loops eliminated both phasic and tonic mechanoreceptor input during either of these hyperpneas. At a given chemical or locomotor stimulus, vagal cooling caused a further increase in costal, crural, parasternal, and rib cage expiratory (triangularis sterni) muscles. No further change in abdominal expiratory muscle activity occurred secondary to vagal cooling during these hyperpneas. However, removal of mechanoreceptor input during hypercapnia was not associated with consistent changes in end-expiratory lung volume, as measured by the He-N2 rebreathe technique. We conclude that during these hyperpneas 1) vagal input is not essential for augmentation of expiratory muscle activity and 2) decrements in abdominal expiratory muscle activity may be offset by increments in rib cage expiratory muscle activity and contribute to the regulation of end-expiratory lung volume. PMID- 1592728 TI - Failure of accentuated vertical body movements to induce cardiac-locomotor coupling. AB - Cardiac-locomotor coupling (CLC) has been reported during a variety of rhythmic human activities. One reason postulated for such coupling is that axial movements of the viscera during some activities (the "visceral piston") may enhance expulsion of blood from the heart; if so, accentuated vertical movements of the body should provide a powerful stimulus to coupling. To test this hypothesis, we studied 20 subjects hopping and 20 others skipping rope for greater than or equal to 10 min while electrocardiographic and force-platform signals were recorded, from which we derived the subjects' exercise and heart rates. The incidence and intensity of apparent coupling in the test subjects were compared with those of cross-over controls, where the heart rate of each subject was related to the hopping or skipping rate of a matched subject. Ratios consistent with coupling were seen in 10 (50%) hopping subjects under test conditions and in 13 (65%) under control conditions; among skipping subjects, the incidences were 11 (55%) and 10 (50%). In neither group of subjects was the difference in the incidences or the intensities of apparent CLC statistically significant. Our failure to detect CLC while our subjects were hopping or skipping suggests that the visceral piston is unimportant to the CLC phenomenon. PMID- 1592729 TI - Locomotor-respiratory coupling during wheelchair propulsion. AB - Visceral movement due to impact loading is believed to play a role in the locomotor-respiratory coupling (LRC) that has been detected in a number of mammalian species. In the bird and bat species in which LRC has been described, the effect of the wing muscles on the timing of respiration appears to be a dominant influence. To test the hypothesis that LRC occurs in humans propelling wheelchairs (where there is no impact loading and the arms are used for locomotion), we studied 10 wheelchair athletes on a motorized treadmill at three speeds. Each subject's data were analyzed by spectral analysis (based on the fast Fourier transform), which detected apparent LRC (rates within 1% of a single digit integer ratio) in 12 (40%) of the 30 test settings. However, a control analysis, in which each subject's arm-thrust rates were compared with another subject's breathing rates, revealed apparent (but false) coupling in 8 (27%), not significantly less often (using the chi 2 test). These findings appear to refute the hypothesis that LRC occurs during wheelchair propulsion. These data are consistent with the theory that the visceral piston is important to LRC and suggest that rhythmic arm movements are insufficient to induce the phenomenon in this setting. PMID- 1592730 TI - Determination of heat debt in the cold: partitional calorimetry vs. conventional methods. AB - Measurements of core temperature (Tc) at different sites produce on some occasions different cooling curves in cold-exposed humans, suggesting that the corresponding thermometric heat debts (HD) could be equally different when calculated by conventional methods [via the change in either Tc or mean body temperature (Tb)]. The present study also compared these thermometric HD values with the calorimetric HD obtained by partitional calorimetry (S). Nine subjects who showed similar initial but different final Tc [rectal (Tre) and auditory canal temperatures (Tac)] during nude cold exposure (2 h at 1 degrees C at rest) were used. Tc-derived HD corresponded to a heat gain of 12 +/- 21 kJ and an HD of 78 +/- 20 kJ with use of Tre and Tac, respectively, whereas the Tb-derived HD varied from 266 +/- 35 to less than or equal to 1,479 +/- 71 kJ with the use of various well-known Tb weighing coefficients. In contrast, S corresponded to 504 +/- 79 kJ, a level that could have been obtained only if the thermoneutral/cold Tb weighing coefficients had been 0.818/0.818 for Tre and 0.865/0.865 for Tac. The results demonstrate that calculation by conventional methods can markedly overestimate or underestimate HD. These differences could not be explained by the site chosen to represent Tc, inasmuch as about the same effect was observed with use of either Tre or Tac. It is concluded that the thermometric value of HD in the cold is not, at least under the present conditions, as accurate and reliable as S. PMID- 1592731 TI - Pulmonary hemodynamics and tissue damage after one lung infusion of Pseudomonas aeruginosa in sheep. AB - The relative roles of hematogenous mediators and direct bacterial toxicity due to phagocytosis by pulmonary intravascular macrophages were determined by selective bacterial infusion into the left pulmonary artery and comparison of right and left lungs at 24 h. Chronically instrumented sheep received 15-min pulmonary arterial infusions of live Pseudomonas aeruginosa (0.35-2.9 x 10(9), n = 6) or saline (n = 5). The saline group demonstrated stable cardiopulmonary function over time. Left lung blood flow, measured by Doppler flow probe, decreased 15 min into the bacterial infusion, with a concomitant sevenfold increase in left lung pulmonary vascular resistance index. The right lung pulmonary vascular resistance index doubled at 1 h, in association with increased plasma thromboxane B2 levels. An increase in cardiac index and decrease in systemic vascular resistance occurred at 12 h. The wet-to-dry weight ratio of the Pseudomonas-infused left lung was increased compared with that of the sham-infused lung. The tissue count of neutrophils in the lungs was doubled in both sides, but neutrophils on the left were more degranulated. The left lung tissue damage was caused by direct bacterial toxicity, including activation of phagocytic cells. Hematogenous mediators induced pulmonary and systemic hemodynamic changes and right lung neutrophil sequestration, but they did not damage the noninfused lung. PMID- 1592732 TI - Mechanical implications of in vivo human diaphragm shape. AB - Using magnetic resonance imaging, we measured the three-dimensional form of the diaphragm in vivo in four supine relaxed subjects at functional residual capacity and calculated its total surface area, the right and left surface areas in the zone of apposition, and the principal radii of curvature as a function of height. The area of apposition comprised 45 +/- 1.5% (SE) of the total surface area of the diaphragm. Available data on the area of the central tendon indicate that a considerable part of the muscular part of the diaphragm is lung apposed. The curvature was linearly related to height over 7 cm of the posterior half of each hemidiaphragm. From the linear portion of this graph and assuming a vertical gradient of transdiaphragmatic pressure of 0.75 cmH2O/cm, we applied the Laplace law and calculated tensions of 54 and 32 g/cm for right and left sides, respectively. We conclude that the shape of at least part of the posterior half of the relaxed human diaphragm in the supine position at functional residual capacity can be explained by the Laplace law, suggesting that both the lung and abdominal contents behave sufficiently as fluids so that they do not impose their shape on the diaphragm. Because diaphragm muscle is partly lung apposed, it is unlikely that the diaphragm functions simply as a piston. PMID- 1592733 TI - Clearance of 99mTc-DTPA and experimentally increased alveolar surfactant content. AB - We measured clearance of 99mTc-labeled diethylenetriamine pentaacetic acid (99mTc DTPA) in rabbits with experimentally increased alveolar surfactant content. In one group of animals, surfactant production was increased by treatment with ambroxol, and another group of animals was treated with tracheal instillation of natural surfactant. A group of untreated control animals and animals treated with instillation of saline were also studied. Clearance was measured during standard conditions of mechanical ventilation and during ventilation with large tidal volumes. In ambroxol- and surfactant-treated groups, clearance rate was reduced compared with untreated control animals. In contrast, clearance rate increased after saline instillation. The differences were observed at both modes of ventilation. The findings indicate that the pulmonary surfactant system is a rate limiting factor for the clearance of 99mTc-DTPA and that the volume dependence of clearance is not explained by stretching of the alveolar wall only. PMID- 1592734 TI - Endothelin-3 is a potent pulmonary vasodilator in the rat. AB - The properties of endothelin-3 (ET-3) were investigated in isolated pulmonary artery rings and isolated blood-perfused lungs of the rat. ET-3 elicited a concentration-dependent relaxation of pulmonary artery rings, and effect inhibited by the nitric oxide synthesis inhibitor L-NG-monomethyl-L-arginine. At 0.1 microM, the response to ET-3 was biphasic, resulting in a sustained contraction. In the isolated lung, ET-3 caused a dose-dependent increase in pulmonary arterial pressure. In lungs ventilated with 3% oxygen, 10 nM ET-3 completely reversed the resultant hypoxic vasoconstriction (HPV) by 100 +/- 8%, an effect unchanged by either indomethacin (1 microM) or glibenclamide (10 microM). L-NG-monomethyl-L-arginine attenuated both the ET-3 dilation in prostaglandin F2 alpha-constricted lungs and the dose-dependent vasodilation of HPV by acetylcholine. ET-3 (10 nM) showed the response time to peak pulmonary arterial pressure generation by hypoxia, the size of the response being unchanged. These results demonstrate that ET-3 has both vasodilator and constrictor actions in the rat lung and that, like acetylcholine, the former is mediated in part via the release of nitric oxide. ET-3 also has the ability to modulate HPV. PMID- 1592735 TI - Contractile properties of the rat external abdominal oblique and diaphragm muscles during development. AB - We studied the in vitro contractile and fatigue properties of the rat external abdominal oblique (EAO) and costal diaphragm (DIA) muscles during postnatal development. Isometric twitch contraction (CT) and half-relaxation (RT1/2) times were longer in both the EAO and DIA muscles during the early postnatal period and decreased with age. In the first postnatal week, the CT and RT1/2 were longer in the EAO than the DIA muscle. At 14 days of age and thereafter, the CT and RT1/2 were shorter in the EAO than in the DIA muscle. Force-frequency relationships of the EAO and DIA muscles changed during postnatal development such that the relative force (percent maximum) generated at lower frequencies (less than 15 pulses/s) decreased with age. Moreover the relative force generated by the EAO muscle at lower frequencies was greater than that of the DIA muscle during the early postnatal period but less than that of the DIA muscle in adults. The specific force of both the EAO and DIA muscles increased progressively with age. There were no differences in specific force between the EAO and DIA muscles at any age. The fatigability of the EAO and DIA muscles was comparable during the early postnatal period and increased in both muscles with postnatal development. In adults the EAO muscle was more fatigable than the DIA muscle. We conclude that the contractile and fatigue properties of the EAO and DIA muscles undergo significantly different postnatal transitions, which may reflect their functional involvement in sustaining ventilation. PMID- 1592737 TI - Adaptations of diaphragm and medial gastrocnemius muscles to inactivity. AB - The effects of 2 wk of inactivity on in vitro contractile properties of diaphragm and medial gastrocnemius (MG) muscles were examined in adult hamsters. In addition, inactivity effects on fiber-type proportions and cross-sectional areas were studied. Inactivity of the right hemidiaphragm or MG muscle was induced by either tetrodotoxin (TTX) blockade of nerve impulses or denervation (DNV). Inactivity effects on diaphragm or MG were compared with corresponding sham (saline-treated or untreated control) muscles. After both TTX- and DNV-induced inactivity, isometric twitch contraction and half-relaxation times were prolonged, maximum tetanic force decreased, and fatigue resistance improved. Proportions of type I and II fibers in both diaphragm and MG were unaffected by TTX- and DNV-induced inactivity. However, in both muscles, type I fibers hypertrophied, whereas type II fibers atrophied. In diaphragm, contractile and morphometric adaptations after DNV were generally more pronounced than those induced by TTX. In addition, compared with corresponding untreated or saline treated control groups, inactivity effects (both TTX and DNV) on MG were generally greater than those induced in diaphragm, with the exception of hypertrophy of type I fibers. We conclude that inactivity exerts differential effects on type I and II fibers in both diaphragm and MG. Yet, these morphometric adaptations cannot completely account for the adaptations in muscle contractile and fatigue properties after inactivity. PMID- 1592736 TI - Effects of sprint training on maximal stroke volume of rats with a chronic myocardial infarction. AB - The hemodynamic response to maximal exercise was determined in rats with a chronic myocardial infarction (MI) that were subjected to 6-8 wk of high intensity sprint training (HIST) or limited exercise activity (sedentary control). Training was performed 6 days/wk and consisted of five 1-min bouts of treadmill running at work loads (15% grade, 97 m/min) in excess of the animal's maximal O2 uptake (VO2max). The left ventricular infarct size for the HIST and sedentary control rats was 35 +/- 4 and 34 +/- 3% of the total endocardial circumference, respectively. VO2max was significantly greater for MI rats subjected to the HIST paradigm than for sedentary control rats. This increase in VO2max was due to an increase in the maximal stroke volume that could be generated by the HIST rat during exercise, inasmuch as the maximal heart rate response and the ability to extract O2 from the blood were similar between the two groups of rats. Citrate synthase activities measured in the plantaris muscle of the HIST and sedentary control rats were similar. These results suggest that the increase in VO2max produced with HIST in MI rats may be linked to changes in central cardiac function, as indicated by the increase in maximal stroke volume that could be generated by the MI rat during maximal exercise conditions. PMID- 1592738 TI - Oxygen-dependent reperfusion injury in the isolated rat lung. AB - To further define the relationship between oxygen dependence of lung injury during ischemia and ischemia-reperfusion, we used the isolated, perfused, and ventilated rat lung model, so that oxygenation and perfusion could be separated. During ischemia, lungs were ventilated with various oxygen concentrations and then ventilated with 95% oxygen during the 60-min reperfusion period. Other lungs were ventilated with 0% oxygen (nitrogen) during ischemia, and the reperfusion phase oxygen concentration was varied. Tissue and perfusate lipid peroxidation products (thiobarbituric acid-reactive substances and conjugated dienes), dry-to wet weight ratio, and lactate dehydrogenase were measured as indexes of lung damage. In addition, electron microscopy of some lungs was performed. Results demonstrate an oxygen dependence of lipid peroxidation in both the ischemic and reperfusion phases, but lipid peroxidation is severalfold greater in the reperfusion than in the ischemic phase. Products of lipid peroxidation closely correlate with indexes of lung injury (dry-to-wet weight ratio, lactate dehydrogenase, and electron microscopy). PMID- 1592739 TI - Action of human respiratory muscles inferred from finite element analysis of rib cage. AB - The actions of several human respiratory muscles have been inferred from finite element analysis of the rib cage. The human model is based on anatomic and mechanical measurements in dogs and human cadavers. As in an earlier canine model, the external and internal (interosseous) intercostal muscles were found to cause, respectively, inspiratory and expiratory displacements of the rib cage, in agreement with the two-dimensional geometric analysis of Hamberger. When extended to three dimensions, Hamberger's analysis helps explain why muscles at the side of the rib cage produce changes in the anteroposterior diameter, whereas muscles at the front and back of the rib cage cause changes in the transverse diameter. PMID- 1592740 TI - Structural changes in elastic fibers after pancreatic elastase administration in hamsters. AB - Ultrastructural changes in lung parenchymal elastic fibers were studied morphometrically 1, 4, and 12 wk after a single 12-unit dose of pancreatic elastase and in a saline-instilled control group. The mean linear intercept of the parenchymal air spaces was increased in the 1-, 4-, and 12-wk post-elastase instillation groups compared with age-matched controls. The volume of alveolar connective tissue fibers predominantly composed of elastin (elastic fibers) was decreased by 35% 1 wk after the instillation of elastase but returned to control levels by 4 wk. Although the total volume of elastic fibers was normal 12 wk after instillation of elastase, the volume of elastic fibers in alveolar entrance rings remained significantly reduced. In serial sections of elastic fibers, numerous gaps or separations in the normally continuous band of elastic fibers that encircle each alveolus were identified 1 wk after elastase instillation. There were 169 +/- 8 (SE), 62 +/- 32, and 12 +/- 6 gaps per millimeter of alveolar entrance ring circumference at 1, 4, and 12 wk, respectively, in the elastase-treated groups. The number of gaps at 12 wk was equivalent to two gaps or discontinuities in the elastic fibers of every alveolar entrance ring. No gaps or separations in elastic fibers were detected at 1, 4, or 12 wk in the control groups. These defects occur in concordance with the progression of air space enlargement and presumably contribute to the progression of air space enlargement that occurs after the elastin content of the tissue has returned to normal. PMID- 1592741 TI - Effects of inspiratory loading on left ventricular myocardial blood flow and metabolism. AB - With airways obstruction, mean pleural pressure decreases. It has been postulated that associated increases in left ventricular afterload increase myocardial O2 demand (MvO2) and coronary blood flow (CBF). We tested this hypothesis in 12 anesthetized mixed-breed dogs. Through a median sternotomy, dogs were instrumented for the measurement of mean arterial pressure, cardiac output, and left anterior descending CBF. A catheter placed in the coronary sinus allowed sampling of left ventricular venous blood. MvO2 was calculated as CBF x (arteriovenous content difference), and coronary resistance was calculated as (mean arterial pressure)/CBF. After closure of the thoracotomy, animals were studied before and during inspiratory threshold loading (IL) of -20 to -25 cmH2O while breathing 100% O2 before and after bilateral cervical vagotomy. During IL, heart rate fell [approximately 20 beats/min (NS prevagotomy, P less than 0.05 postvagotomy)], arterial PCO2 increased [45 to 66 Torr prevagotomy, 45 to 50 Torr postvagotomy (P less than 0.01)], and arterial O2 content was unchanged. CBF increased with IL:41% prevagotomy (P less than 0.01), 18% postvagotomy (P less than 0.02). However, with IL, MvO2 did not increase significantly either pre- or postvagotomy. Coronary resistance decreased with IL [30% prevagotomy, 24% postvagotomy (P less than 0.01)]. In eight dogs, PCO2 was increased by increasing dead space while the animals were mechanically ventilated and paralyzed. Although there was little change in CBF, heart rate fell by an amount equal to that with IL. We conclude that 1) IL causes coronary vasodilation not related to changes in MvO2, PCO2, or vagal tone; 2) MvO2 does not increase with IL; and 3) decreased heart rate with IL is related to hypercapnia and/or acidosis. PMID- 1592742 TI - Hepatic dysoxia commences during O2 supply dependence. AB - Hepatic O2 consumption (VO2) remains relatively constant (O2 supply independent) as O2 delivery (DO2) progressively decreases, until a critical DO2 (DO2c) is reached below which hepatic VO2 also decreases (O2 supply dependence). Whether this decrease in VO2 represents an adaptive reduction in O2 demand or a manifestation of tissue dysoxia, i.e., O2 supply that is inadequate to support O2 demand, is unknown. We tested the hypothesis that the decrease in hepatic VO2 during O2 supply dependence represents dysoxia by evaluating hepatic mitochondrial NAD redox state during O2 supply independence and dependence induced by progressive hemorrhage in six pentobarbital-anesthetized dogs. Hepatic mitochondrial NAD redox state was estimated by measuring hepatic venous beta hydroxybutyrate-to-acetoacetate ratio (beta OHB/AcAc). The value of DO2c was 5.02 +/- 1.64 (SD) ml.100 g-1.min-1. The beta-hydroxybutyrate-to-acetoacetate ratio was constant until a DO2 value (3.03 +/- 1.08 ml.100 g-1.min-1) was reached (P = 0.05 vs. DO2c) and then increased linearly. Peak liver lactate extraction ratio was 15.2 +/- 14.1%, occurring at a DO2 of 5.48 +/- 2.54 ml.100 g-1.min-1 (P = NS vs. DO2c). Our data support the hypothesis that the decrease in VO2 during O2 supply dependence represents tissue dysoxia. PMID- 1592743 TI - Training-induced alterations in young and senescent rat diaphragm muscle. AB - The current study sought to examine the effects of chronic endurance treadmill running on oxidative capacity and capillary density in specific diaphragm muscle fiber types in young (5 mo) and senescent (greater than or equal to 23 mo) female Fischer 344 rats. Both young and senescent animals trained at approximately 75% of maximal O2 consumption for 1 h/day 5 days/wk for 10 wk. Plantaris citrate synthase activity was significantly increased (P less than 0.01) in both young and old trained groups. Densitometric analysis of succinate dehydrogenase (SDH) activity in diaphragm type I, IIa, and IIb muscle fibers was done using a computerized image-processing system. There were no age-related differences in SDH activity between the young and old groups for any of the fiber types. In addition, SDH activity was found to be significantly increased (P less than 0.05) in all three fiber types in both the young and senescent trained animals compared with their sedentary counterparts. Fiber size and capillary density did not differ between young and senescent rats, nor did exercise affect this measure. Each fiber, irrespective of type, had an average of approximately four capillaries in contact with it. However, type IIb fibers had a significantly lower capillary density per unit area than type I or IIa muscle fibers. The results indicate that the senescent costal diaphragm maintains its ability to adapt to an increased metabolic demand brought about by locomotor exercise. Of further interest is the finding that training adaptations occurred in all three fiber types, suggesting that increased work of breathing from moderate exercise leads to recruitment of all three fiber types.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592744 TI - Effects of resistance training on elbow flexors of highly competitive bodybuilders. AB - The influence of gender on muscular adaptation of the elbow flexors to 24 wk of heavy resistance training was studied in five male bodybuilders (MB) and five female bodybuilders (FB) who were highly competitive. Muscle cross-sectional area (CSA), fiber area, and fiber number were determined from the biceps brachii, and voluntary elbow flexor torque was obtained at velocities of contraction between 0 and 300 degrees/s. Biceps and flexor CSA was 75.8 and 81% greater, respectively, in MB than in FB, but muscle CSA was not significantly altered by the training program in either group. Because estimated fiber number and the volume density of nonmuscle tissue were similar in MB and FB, most of the gender difference in muscle CSA appeared to be due to greater absolute mean fiber areas in MB (10.51 and 10.68 x 10(3) microns 2 pre- and posttraining, respectively) than in FB (5.33 and 5.96 x 10(3) microns 2 pre- and posttraining, respectively). In neither MB nor FB did fiber type achieve further hypertrophy during the 24-wk training program. These data suggest that the extent of any change in muscle mass or muscle fiber characteristics is minimal after a bodybuilder of either gender has attained a high degree of muscle mass and a highly competitive status. PMID- 1592745 TI - Triangularis sterni and phrenic nerve responses to progressive brain hypoxia. AB - Activity of the respiratory muscles that are not normally active during eupnea (genioglossal and abdominal) has been shown to be more vulnerable to hypoxic depression than inspiratory diaphragmatic activity. We hypothesized that respiratory muscles that are active at eupnea would be equally vulnerable to isocapnic progressive brain hypoxia (PBH). Phrenic (PHR) and triangularis sterni nerve (TSN) activity were recorded in anesthetized peripherally chemodenervated vagotomized ventilated cats. Hypercapnia [arterial PCO2 (PaCO2) = 57 +/- 3 (SE) Torr] produced parallel increases in peak PHR and TSN activity. PBH [0.5% CO-40% O2-59.5% N2, arterial O2 content (CaO2) reduced from 13.1 +/- 1.0 to 3.7 +/- 0.3 vol%] resulted in parallel decreases of peak PHR and TSN activity to neural apnea. PBH was continued until PHR gasping ensued (CaO2 = 2.9 +/- 0.2 vol%); TSN activity remained silent during gasping. After 6-12 min of recovery (95% O2-5% CO2; CaO2 = 7.8 +/- 0.8 vol%; PaCO2 = 55 +/- 2 Torr), peak PHR activity was increased to 110 +/- 18% (% of activity at 9% CO2) whereas peak TSN activity was augmented to 269 +/- 89%. The greater augmentation of TSN activity during the recovery period could not be explained solely by hypercapnia. In conclusion, we found that 1) TSN expiratory and PHR inspiratory activities are equally vulnerable to hypoxic depression and 2) recovery from severe hypoxia is characterized by a profound augmentation of TSN expiratory activity. PMID- 1592746 TI - Attenuation of platelet-activating factor-induced airway responses with methylprednisolone succinate in sheep. AB - Intratracheal instillation of platelet-activating factor (PAF) in sheep produces bronchoconstriction and airway hyperresponsiveness (AHR) by a two-stage process that involves the initial stimulation of PAF receptors followed by the secondary generation of proinflammatory mediators. Because the biological effects of PAF may be mediated by these proinflammatory metabolites, it is possible that a steroidal anti-inflammatory agent would modify the airway responses of PAF. We measured specific lung resistance (sRL) in sheep (n = 11) before, immediately after, and serially for up to 2 h after intratracheal instillation of PAF (30 micrograms/kg). Airway responsiveness was measured 2 h post-PAF when sRL had returned to baseline and was expressed as the cumulative provocating dose of carbachol that increased sRL to 4 l.cmH2O.l-1.s (PD4). PD4 was determined on a control day and on different experiment days without or after treatment with intravenous methylprednisolone (MPS; 1 mg/kg) administered 3 h before (n = 6), 20 min before PAF (n = 7), or 20 min after PAF challenge (n = 7). PAF increased sRL by 222 +/- 44% (SE) above baseline and decreased PD4 of carbachol by 44 +/- 5% (P less than 0.05). Pretreatment (both 3 h and 20 min) with MPS attenuated the PAF induced increases in sRL, whereas its administration 20 min post-PAF had no effect. Irrespective of the effects on sRL, MPS administration inhibited the PAF induced AHR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592747 TI - Relationship between axial motion and volume displacement of the diaphragm during VC maneuvers. AB - During semistatic inspiratory and expiratory vital capacity (VC) maneuvers, axial motion of the diaphragm was measured by lateral fluoroscopy and was compared with diaphragmatic volume displacement. Axial motion was measured at the anterior, middle, and posterior parts of the diaphragm, and the mean of these measurements was used. The volume displacement was calculated in two ways: first, from respiratory inductive plethysmograph-(Respitrace) derived cross-sectional area changes of rib cage and abdomen (Vdi,RIP) by means of a theoretical analysis described by Mead and Loring (J. Appl. Physiol. 53: 750-755, 1982) and, second, from fluoroscopically measured changes in position and anteroposterior surface of the diaphragm (Vdi,F). A very good linear relationship was found between Vdi,RIP and Vdi,F during inspiration as well as expiration (r greater than 0.95), indicating that the analysis of Mead and Loring was valid in the conditions of the present study. The diaphragmatic volume displacement (active or passive) accounted for 50-60% of VC. A very good linear relationship was also found between mean axial motion and volume displacement of the diaphragm measured with both methods during inspiration and expiration (r greater than 0.98). Our data suggest that, over the VC range, diaphragmatic displacement functionally can be represented by a pistonlike model, although topographically and anatomically it does not behave as a piston. PMID- 1592748 TI - Predicting the time of occurrence of decompression sickness. AB - Probabilistic models and maximum likelihood estimation have been used to predict the occurrence of decompression sickness (DCS). We indicate a means of extending the maximum likelihood parameter estimation procedure to make use of knowledge of the time at which DCS occurs. Two models were compared in fitting a data set of nearly 1,000 exposures, in which greater than 50 cases of DCS have known times of symptom onset. The additional information provided by the time at which DCS occurred gave us better estimates of model parameters. It was also possible to discriminate between good models, which predict both the occurrence of DCS and the time at which symptoms occur, and poorer models, which may predict only the overall occurrence. The refined models may be useful in new applications for customizing decompression strategies during complex dives involving various times at several different depths. Conditional probabilities of DCS for such dives may be reckoned as the dive is taking place and the decompression strategy adjusted to circumstance. Some of the mechanistic implications and the assumptions needed for safe application of decompression strategies on the basis of conditional probabilities are discussed. PMID- 1592749 TI - Mechanisms of pulmonary vasoconstriction induced by chemotactic peptide FMLP in isolated rabbit lungs. AB - The chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been shown to constrict both bronchial and coronary vascular smooth muscle through the action of cyclooxygenase or lipoxygenase products. We observed that intravenous FMLP increased pulmonary vascular resistance (PVR) in isolated buffer-perfused rabbit lungs. FMLP increased the PVR (primarily in the middle segment of the pulmonary vascular bed) at concentrations greater than or equal to 10(-7) M. Maximum vasoconstriction occurred at 5 min and then slowly declined to a level that remained above baseline at 30 min. Tachyphylaxis was observed in response to FMLP. When polymorphonuclear leukocytes (PMNs) were added to the perfusate, FMLP caused a greater increase in PVR. PMN depletion with dimethylmyleran significantly reduced the PVR response to FMLP. Pretreatment with two dissimilar cyclooxygenase inhibitors, meclofenamate and ibuprofen, and the leukotriene synthesis blocker MK 886 had no effect on the FMLP-induced vasoconstriction. However, the reactive oxygen species scavenger catalase significantly reduced the vasoconstriction. These results suggest that FMLP induces vasoconstriction that is dependent on PMNs and mediated by reactive oxygen species with no involvement of cyclooxygenase or lipoxygenase products. PMID- 1592750 TI - Convective and diffusive gas transport in canine intrapulmonary airways. AB - The significance of convective and diffusive gas transport in the respiratory system was assessed from the response of combined inert gas and particle boluses inhaled into the conducting airways. Particles, considered as "nondiffusing gas," served as tracers for convection and two inert gases with widely different diffusive characteristics (He and SF6) as tracers for convection and diffusion. Six-milliliter boluses labeled with monodisperse di-2-ethylhexyl sebacate droplets of 0.86-microns aerodynamic diameter, 2% He, and 2% SF6 were inspired by three anesthetized mechanically ventilated beagle dogs to volumetric lung depths up to 170 ml. Mixing between inspired and residual air caused dispersion of the inspired bolus, which was quantified in terms of the bolus half-width. Dispersion of particles increased with increasing lung depth to which the boluses were inhaled. The increase followed a power law with exponents less than 0.5 (mean 0.39), indicating that the effect of convective mixing per unit volume was reduced with depth. Within the pulmonary dead space, the behavior of the inert gases He and SF6 was similar to that of the particles, suggesting that gas transport was almost solely due to convection. Beyond the dead space, dispersion of He and SF6 increased more rapidly than dispersion of particles, indicating that diffusion became significant. The gas and particle bolus technique offers a suitable approach to differential analysis of gas transport in intrapulmonary airways of lungs. PMID- 1592751 TI - Durability of the reproductive axis in eumenorrheic women during 1 yr of endurance training. AB - Menstrual cycle (MC) alterations occur in some endurance-training women. We hypothesized that a prospective running program would evoke alterations in MC phase lengths and in the physiological frequency of pulses of luteinizing hormone (LH) and/or diminish 24-h integrated serum LH concentrations in some women. In addition, we postulated that women who train more intensively (above the lactate threshold) would show alterations in gonadotropin release earlier in the training program or to a greater degree. To test these hypotheses, we examined the effects of different exercise intensities on physiological and endocrine responses. Twenty-three healthy eumenorrheic gynecologically mature (postmenarchal age 17.8 +/- 0.9 yr) untrained women undertook a 1-yr training program at one of two exercise intensities, one at a velocity corresponding to the lactate threshold (LT) and the other halfway between that of LT and peak running velocity, or served as controls. Training distance was the same in each exercise group. Physiological measurements were repeated every four MC to track changes in fitness and readjust training velocities. The lengths of the MC and the follicular and luteal phases were determined from hormonal concentrations. Body composition, nutritional intake, and pulsatile release of LH were determined. The women ran approximately 790 miles. Each group improved physiologically, with the greater than LT group improving to a greater degree. A less than 2-day decrease in the luteal phase length was observed only in the greater than LT group. No significant changes for any parameter of pulsatile LH release were noted between exercise groups. No significant changes in nutritional intake and only small changes in body composition were noted in either exercise group despite the added energy expenditure of exercise. We conclude that a progressive exercise program of moderate distance and intensity does not adversely affect the robust reproductive system of gynecologically mature eumenorrheic women. PMID- 1592752 TI - Thermoregulation during rest and exercise in the cold in pre- and early pubescent boys and in young men. AB - Eight minimally dressed pre- and early pubescent boys (age 11-12 yr) and 11 young adult men (age 19-34 yr) rested for 20 min and exercised on a cycle ergometer for 40 min at approximately 30% of their maximum oxygen consumption (VO2max) at 5 degrees C. To quantify the added increase in metabolic rate because of cold, a separate test was carried out at 21 degrees C at rest and at equal work rates as in the cold. Both groups were similar in subcutaneous fat thickness and VO2max per kilogram body weight. Rectal temperature increased slightly during the exposure to the cold, but no significant difference was observed between the boys and men. In the cold, the boys had lower skin temperatures than the adults in their extremities but not in the trunk. The boys increased their metabolic rates in the cold more than did the men. As a result, the boys maintained their core temperature as effectively as the adults. Similar age-related differences in thermoregulatory responses to cold were observed when two boys and two men with equal body sizes were compared. Our results suggest that there may be maturation related differences in thermoregulation in the cold between children and adults. PMID- 1592753 TI - Coordination between cardiovascular and respiratory control systems during and after cerebral ischemia. AB - The dissociation of cardiovascular (arterial hypertension) and respiratory (depression) reactions to severe cerebral ischemia seems to be inconsistent with the usual cooperative behavior of the two systems and their role in managing disturbances in the central chemical environment. In the present study the Cushing reaction was elicited by transient increase of the intracranial pressure 4-11 times in each experiment. The pressor response and changes in the vertebral sympathetic nerve discharge (SND) were compared with the respiratory reaction and with changes in the phrenic nerve activity. The reaction in both nerves developed in two phases. In the phrenic nerve, an initial hyperactivity (increased discharge amplitude and frequency) coincided with augmentation of the rhythmic SND (phase 1) and complete nerve depression developed when the SND was desynchronized (phase 2). The transition in both systems correlated in their latencies and the severity of the ischemia needed for their stimulation. Repetition of the ischemic stimuli increased the occurrence of the respiratory related rhythmicity in the SND and later changed its character from rhythmic amplitude modulation to respiratory-related high-frequency bursting SND coinciding with the inspiration. It is concluded that, despite the apparent dissociation between the cardiovascular and respiratory reactions, there is a parallel response between the neurophysiological correlates of the two systems to increasing severity of cerebral ischemia. PMID- 1592754 TI - Work of adhesion of respiratory tract mucus. AB - A method was devised to measure the work of adhesion (WA) to a substrate of mucus, a viscoelastic gel, from the measured contact angle of glycerol on a mucus substrate and the known physical properties of a Teflon surface. Fifteen sputum samples from cystic fibrosis (CF) patients were compared with 25 mucus samples from canine tracheal pouches (CP), studied in the hydrated and partially dehydrated states. Apparent viscosity (eta A) and recoverable shear strain (SR) were measured by fluxgate magnetometry, and water content was inferred from vapor pressure osmometry. Na+, K+, and Ca2+ concentrations were measured with specific ion electrodes and Cl- with a chloridimeter. The Cl- concentration of the CP mucus was inversely proportional to its osmolality, and the Cl- concentration of the CP mucus was 102.5 +/- 1.6 meq/l compared with 55.6 +/- 2.5 meq/l for CF sputum. When CP mucus osmolality was increased from 316.0 +/- 5.5 to 430.0 +/- 7.5 mosmol/kg, WA increased from 25.1 +/- 1.8 to 31.1 +/- 1.2 ergs/cm2 and eta A increased from 391 +/- 55 to 622 +/- 121 P, respectively. CF sputum WA was 30.2 +/- 0.6 ergs/cm2, eta A was 1,110 +/- 316 P, and osmolality was 466.0 +/- 14.0 mosmol/kg. The increased WA and eta A of mucus in CF patients may thus be dependent on the hydration of mucus, which is related to the documented Cl- transport defect. PMID- 1592755 TI - Use of ionic and zwitterionic (Tris/BisTris and HEPES) buffers in studies on hemoglobin function. AB - The functional characteristics of hemoglobin (Hb) depend on oxygenation-linked proton and anion binding and thus on solvent buffer groups and ionic composition. This study compares the oxygenation properties of human Hb in ionic [tris(hydroxymethyl)aminomethane (Tris) and BisTris] buffers with those in zwitterionic N-2-hydroxy-ethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer under strictly controlled chloride concentrations at different pH values, two temperatures, and in the absence and presence of the erythrocytic cofactor, 2,3 diphosphoglycerate (DPG). In contrast to earlier studies (carried out at the same or different chloride concentrations) it shows only small buffer effects that are manifested at low chloride concentration and high pH. These observations suggest chloride binding to the Tris buffers, which reduces the interaction with specific chloride binding sites in the Hb. The findings indicate that HEPES allows for more accurate assessment of Hb-oxygen affinity and its anion and temperature sensitivities than ionic buffers and advocates standard use of HEPES in studies on Hb function. Precise oxygen affinities of Hb dissolved in both buffers are defined under standard conditions. PMID- 1592756 TI - Fiber-optic transmission catheter for regional venous oxygen saturation and blood flow. AB - We have developed a method for monitoring regional venous oxygen saturation. The key feature of this system is the use of highly flexible polymer fiber optics, and this flexibility allowed the production of a new fiber-optic transmission catheter. The space between the "face-to-face" positioned fiber-optic tips forms a remote catheter-based transmission cell. Our method applies Twersky's theory, in which absorption and scattering can be treated independently. Fresh rabbit blood was pumped through a disk oxygenator in which gas exchange occurred and passed the catheter. Simultaneous results obtained by the catheter and a cuvette oximeter were excellent (r = 0.99, SD = 1.1%). Oxygen saturation measured by this catheter was independent of vessel wall artifacts, blood pH, and flow velocity. Another application of this method is measurement of blood flow by the dye- (indocyanine green) dilution technique. The results of flow measurements by the catheter appeared to be satisfactory (r = 0.99, SD = 1.7%). This study concludes that our method is effective for monitoring the balance between regional oxygen supply and demand. PMID- 1592757 TI - Phrase-spaced formats improve comprehension in average readers. AB - College readers read and answered questions on 12 short essays. Essays formatted so that points between phrases had fractional extra space added to them were comprehended better than normally formatted text. These improvements were specific to average readers. Practically, the results justify classroom research on the benefits of phrase-sensitive formatting; theoretically, the results add to existing evidence that poor to average readers specifically lack perceptual strategies for grouping word sequences into phrases. PMID- 1592758 TI - Effects of alternative modeling strategies on outcomes of interpersonal-skills training. AB - The effects of two alternative modeling strategies-using multiple scenarios and combining negative and positive model displays-on outcomes of a behavior modeling training program were explored. Trainees (N = 72) participated in a program on assertive communication structured to allow for a controlled experimental design that crossed scenario variability (one vs. multiple scenarios) with model display variability (positive model displays vs. positive and negative model displays). Outcomes assessed included trainee reactions, learning, and retention and behavioral measures of reproduction and generalization. The effects of multiple scenarios were negligible, but the positive and negative combination of model displays had a significant positive effect on trainee generalization and a significant negative effect on reproduction. Implications for future modeling research and practice are discussed. PMID- 1592759 TI - Cohesion in the discourse interaction of autistic, specifically language impaired, and normal children. AB - This study examines discourse cohesion in young normal, specifically language impaired, and autistic children. The Halliday and Hasan (1976) approach was applied to investigate cohesion strategies used in interactive discourse by 10 autistic, 8 specifically language-impaired, and 8 normal children matched for language age (MLU, receptive vocabulary and syntax). The following questions were investigated: (a) Do all three groups use the same cohesion strategies in their discourse, and if so, do they use these strategies with the same rate and with the same patterning? (b) What can be said with respect to the errors the individual groups make? Results showed that all three groups used the same cohesion strategies. All groups were similar in patterning. Significant group differences were found in the overall rate of correct use and in the use of individual cohesive ties. The groups also differed significantly in overall error rates, and error rates related to individual tie categories. Results are discussed from the perspective of possible variables contributing to group differences. Frequency of occurrence in natural discourse is discussed in terms of specific cohesive strategies used by the children. PMID- 1592760 TI - Brief report: autism and herpes simplex encephalitis. PMID- 1592762 TI - Brief report: a girl aged two years and seven months with autistic disorder videotaped from birth. PMID- 1592761 TI - Brief report: attention performance in autism and regional brain metabolic rate assessed by positron emission tomography. PMID- 1592763 TI - Plasma beta-endorphin concentrations in autism. PMID- 1592764 TI - Sensitivity and specificity of the Behavioral Summarized Evaluation (BSE) for the assessment of autistic behaviors. AB - The Behavior Summarized Evaluation (BSE), developed for the assessment of autistic behavior, was specifically designed to evaluate the severity of behavioral problems in autistic children involved in bioclinical and therapeutic studies. The reliability studies and the factorial analysis of this scale have been previously published. The present paper examines the effectiveness of the BSE to discriminate 58 autistic from 58 nonautistic mentally retarded children. The BSE clearly separated the two samples of children. A most efficient combination of 8 items emerged from the stepwise item selection procedure. The between-group differences were highest on 4 items, indicating that the most particular pattern in autistic compared to nonautistic children could be the association of autistic withdrawal and stereotypic behaviors. Our findings suggest that the BSE could help in the detection and evaluation of autistic developmental deviance. Implications for further research are discussed. PMID- 1592765 TI - Autism by another name? Semantic and pragmatic impairments in children. AB - The literature on children with language disorders that are characterized by semantic and pragmatic impairments is reviewed and the conclusion is drawn that some of these conditions may stem from the same fundamental cognitive and interpersonal difficulties that are found in early childhood autism. A summary is presented of recent relevant research and theory in the field of autism and suggestions are offered on how these ideas might be applied to children showing semantic and pragmatic difficulties. PMID- 1592766 TI - Staff perceptions of reinforcer responsiveness and aberrant behaviors in people with mental retardation. AB - Perceptions by staff of the classes of reinforcers and aberrant behaviors of a sample of 470 people with predominantly severe or profound mental retardation were explored. Principal components analysis of a 45-item survey suggested eight classes of reinforcers: consumable, verbal-speaker, visual-motor, social, physical-contact, passive-observer, play, and academic reinforcers. Stepwise multiple regression was used to predict five classes of maladaptive behaviors as measured by the Aberrant Behavior Checklist (irritability, lethargy, stereotypy, hyperactivity, and inappropriate speech) from the eight classes of reinforcers. Each class of psychopathology was related to a unique set of predictors. All classes of psychopathology could be predicted by staff perceptions of underresponsiveness to social reinforcers and overresponsiveness to consumable reinforcers. The findings of organized structures of reinforcers and their covariation with pathological behaviors have implications for research and intervention as well as theoretical value in defining aberrant behaviors in people with mental retardation. PMID- 1592767 TI - The cutting edge in services for people with autism. AB - The current study assesses the opinions of a select group of professionals in the field of autism. The professionals indicated past progress, described the current status, and identified and clarified the fundamental concerns and issues for the future. This information was obtained to further develop and expand existing intervention programs for individuals with autism, and will be of use in charting the most promising directions for the future. PMID- 1592768 TI - Knowing and practicing ethics. AB - The interrelationship between ethics and child and adolescent psychiatry is discussed, particularly as it relates to clinical practice. Three principles for ethical clinical practice are presented from a philosophical perspective and illustrated with two case vignettes. A formulation is reached that states that ethical theory parallels clinical theory. PMID- 1592769 TI - Ethical perspectives on managed care as it relates to child and adolescent psychiatry. AB - Managed health care is providing an increasing influence in the way child and adolescent psychiatry is practiced. The goals of managed care have been to manage price, service, and quality. As external forces are brought to bear on child and adolescent psychiatry, ethical and legal dilemmas are faced. Underlying principles and the impact of society force physicians to reexamine their values and reeducate themselves about legal developments. PMID- 1592770 TI - Ethical issues in forensic child and adolescent psychiatry. AB - This article addresses the unique ethical conflicts that are encountered in forensic psychiatry. Special issues for the forensic child and adolescent psychiatrist in the areas of custody, sexual abuse, termination of parental rights and adoption, evaluation of juvenile offenders, and maternal-fetal conflicts are addressed. The need for neutrality, objectivity, and integrity in performing forensic evaluations is stressed. PMID- 1592771 TI - Ethical principles governing research in child and adolescent psychiatry. AB - This paper examines the ethical principles governing research in child and adolescent psychiatry. The guidelines for protection of children and adolescents are research subjects are discussed. These include the principle of nonmaleficence and beneficence (the risk-benefit ratio), the principle of autonomy (informed consent and confidentiality), and the principle of justice (fair distribution of benefits and burdens of research). In the light of recent national efforts to help promote responsible research practice, the ethical standards relating to the protection of scientific integrity as well as research advocacy, training, and stewardship are also discussed. PMID- 1592772 TI - An approach to teaching ethics in child and adolescent psychiatry. AB - Examples of ethical dilemmas, emerging in the context of a resident case-centered seminar, are used to illustrate a proposed approach to instruction in ethics for child and adolescent psychiatry residents. In addition to a rudimentary formal didactic curriculum, a teaching methodology is outlined that intentionally focuses on ethical problems, approaches to analyses, proposed courses of action, and attempts at resolution. Four representative issues are utilized: confidentiality, treatment refusal, treatment termination, and the interface of individual and family therapies. Educational objectives include the increased recognition by child and adolescent psychiatry trainees of potential ethical conflicts, of the utility of ethical analyses to inform choices of clinical interventions, and of the desirability of forestalling premature action before attempts at thoughtful resolution. PMID- 1592773 TI - Are attentional-hyperactivity deficits unidimensional or multidimensional syndromes? Empirical findings from a community survey. AB - Factor analysis on teacher ratings of symptoms in a probability community sample of children aged 6 to 16 years (N = 614) yielded two factors: Inattention and Hyperactivity-Impulsivity. Subsequent cluster analyses on the scores of factorially derived scales for a subsample of 170 children with a diagnosis of attention deficit disorder with (ADDH) and without hyperactivity (ADDWO), or normals, resulted in five clusters that accounted for 88% of the variance. The existence of these clusters was confirmed using external validating criteria. The data support a bidimensional conceptualization of attention deficit disorder with hyperactivity, one dimension consisting of symptoms of inattention and another of symptoms of hyperactivity-impulsivity. The data also suggests that a condition very similar to the DSM-III-R description of undifferentiated attention-deficit disorder also exists as a distinct entity. PMID- 1592774 TI - Attention deficit disorder with and without hyperactivity: a review and comparison of matched groups. AB - This paper compares attention deficit disorder (ADD) with hyperactivity (ADDH) and without hyperactivity (ADDWO). The literature is outlined, revealing the areas of possible differences to be not only the core symptoms, but also associated conduct and emotional symptoms, social relations functioning, learning, medical disorders, family history, and course and outcome of the disorder. Empirical data are presented comparing age and sex matched groups of children from a speech/language clinic sample with ADDH (N = 40) and ADDWO (N = 40). Although the methods of the present study are different from those of previous studies, they nonetheless support a number of previous findings, and, further, give support to the external validity of the ADDWO diagnostic category. PMID- 1592775 TI - Comorbidity between ADDH and learning disability: a review and report in a clinically referred sample. AB - A widely variable overlap ranging from 10 to 92% has been reported in the literature between attention deficit disorder with hyperactivity (ADDH) and learning disability (LD), most likely a result of inconsistencies in the criteria used to define LD in different studies. The following study seeks to more accurately determine rates of LD in clinically referred children. Using a psychometrically reliable methodological approach, it was expected that the rate of LD in ADDH children would be far more modest than previously reported. Subjects were referred children with ADDH (N = 60), children with academic problems (N = 30), and normal controls (N = 36) of both sexes with available psychological and achievement testing. Using a liberal definition of LD, significant differences were found between the groups (ADDH = 38% versus academic problems = 43% versus normals = 8%; p = 0.002). In contrast, more modest rates were found using two more stringent methods of assessment (23 and 17%; 10 and 3%; 2 and 0%, respectively; p = 0.02). Arithmetic-based LD appears to be equally identified by both stringent methods, whereas the liberal definition overidentified children in all three groups. These findings show that a liberal definition of LD overidentifies LD not only in ADDH children but also in normal children. PMID- 1592776 TI - Psychiatric comorbidity in attention deficit disorder: impact on the interpretation of Child Behavior Checklist results. AB - Studies have investigated associations between the Child Behavior Checklist (CBCL) and clinical diagnoses without assessing the impact of comorbidity on these results. This study evaluates associations between parental reports from the CBCL and a structured diagnostic interview in children with attention deficit disorder with hyperactivity (ADDH) stratified by the presence (ADDH+) or absence (ADDH-) of psychiatric comorbidity. Interview-defined ADDH children scored significantly worse on all scales of the CBCL compared with scores from interview defined non-ill comparisons. However, these findings were accounted for by the subgroup of children with ADDH+. The results indicate a good correspondence between CBCL-based ratings and interview-defined diagnoses. These findings also suggest that the CBCL may be a good screening instrument, not only for ADDH but also for comorbid psychiatric disorders. PMID- 1592777 TI - Effects and noneffects of methylphenidate in children with mental retardation and ADHD. AB - Stimulant medication efficacy was evaluated in 14 children with attention-deficit hyperactivity disorder and IQs of 48 to 74 in a double-blind crossover study of two methylphenidate doses and placebo. Dependent measures included behavioral ratings, work output, measures of learning, attention and impulsivity, and direct observation of peer social interactions. Nine children (64%) were methylphenidate responders, based upon the Conners Hyperactivity Index. Significant gains in on task behavior and attentional skills were noted with methylphenidate in comparison to placebo. No improvement on measures of learning or social interactions were observed. Results extend and replicate previous research conducted by the authors. PMID- 1592778 TI - Methylphenidate in hyperactive boys with comorbid tic disorder: II. Short-term behavioral effects in school settings. AB - In this study, 11 prepubertal hyperactive boys with tic disorder received placebo and three doses of methylphenidate (0.1, 0.3, and 0.5 mg/kg) for 2 weeks each, under double-blind conditions. Each boy was observed for approximately 20 hours in the school setting (classroom seatwork activities, lunchroom, and playground). Results showed that methylphenidate effectively suppressed hyperactive/disruptive behaviors in the classroom and physical aggression in the lunchroom and on the playground. Methylphenidate also reduced the occurrence of vocal tics in the classroom and the lunchroom. None of the motor tic measures revealed drug effects, but the lowest mean rate of motor tics occurred on the 0.3 mg/kg dose. On an operationally defined minimal effective dose, only one boy experienced motor tic exacerbation. PMID- 1592780 TI - Children's concepts of the family. AB - The past decade has witnessed increased research emphasis on children's developing conceptions of their social environment. In the present study, 64 children in grades 1 through 6 were interviewed to examine age-related changes in their understanding of the concept of family. The study also explored whether children's developing conceptions of the family were mediated by their own family structures. Results indicated five levels of family concept understanding that reflected a growing (i.e., age-related) facility in children's application of kinship criteria across traditional and nontraditional family groupings. However, the sophistication of children's understanding of the family was not related to the structure of their own families. These findings suggest that children's level of cognitive development is more important for their comprehension of the family than the specific experiences derived from living within their own unique family. Implications of these findings for mental health professionals who work with families in transition are discussed. PMID- 1592779 TI - The validity of instruments measuring tic severity in Tourette's syndrome. AB - By using four different scales that measure tic severity in Tourette's syndrome, three independent judges concurrently evaluated their validity and interjudge reliability in 20 affected individuals. The Yale Global Tic Severity Scale, Tourette's Syndrome Severity Scale, Tourette's Syndrome-Clinical Global Impression Scale, and the Hopkins Motor and Vocal Tic Scale were equally effective in determining overall severity and showed good interrater reliability. Both historical information and direct observation of the subject were shown to have a significant contribution towards the overall assessment of tic severity. With all instruments, tic symptom ratings were shown to be independent of those for either attention-deficit hyperactivity disorder or obsessive-compulsive disorder. A 67% incidence of behavioral problems and social difficulties was identified by the Child Behavior Checklist. Nevertheless, associations with tic severity were limited to areas showing interference with social relationships and school adjustments. These results extend the understanding of Tourette's syndrome severity scales and provide additional information necessary for the development of a unified rating scale. PMID- 1592782 TI - Is there a relationship between children's mental disorders and their ideal family constructs? AB - Psychiatric outpatients (N = 72) and nonclinical children (N = 72) from 1st to 12th grades portrayed their families as they wished they were (ideal representation), using the Family System Test (FAST), a figure placement technique that focuses on cohesion and hierarchy. Results showed that constructs of ideal family relations were related to age group (1st to 3rd graders versus 4th to 12th graders) and to clinical status (clinical versus nonclinical) but not to the type of mental disorder. First, younger children portrayed less cohesion than did older ones. Second, clinical respondents were less likely to represent cohesive family patterns and were more likely to report ideal family situations as special events. Results are discussed from a developmental as well as from a family systems perspective. PMID- 1592781 TI - The Cornell Interview of Peers and Friends: development and validation. AB - The Cornell Interview of Peers and Friends (CIPF), a 30-minute semistructured interview, evaluated 7- to 11-year-old children's perceptions of their social relationships. Significant differences on the CIPF were found between clinical and nonclinical groups and between boys and girls. Three CIPF subscales, Developmental Appropriateness, Social Skills, and Self-esteem, were assessed and significantly differentiated between clinical and nonclinical populations. Satisfactory interrater reliability is reported for the interview's total score and the three subscale scores. The CIPF offers potential for screening children at risk for emotional disturbance and for assessing outcomes of therapeutic interventions. PMID- 1592783 TI - Psychiatric and family functioning in children with leukemia and their parents. AB - The present study reports data from a cross-sectional investigation of the psychiatric and psychosocial functioning of 55 children diagnosed with acute lymphocytic leukemia and their families at three points in time: diagnosis (newly diagnosed), 1 year postdiagnosis, and 1 year after the completion of chemotherapy (off-therapy). Results reveal minimal psychopathology in these children and their parents based on self- and informant-reports and structured diagnostic interviews. These families appear to be functioning adequately and report more family cohesiveness and marital satisfaction after chemotherapy was completed. Coping strategies commonly used by children and their parents include problem solving, a positive outlook, and good communication. Implications for psychiatric consultation are presented. PMID- 1592784 TI - Identifying children in the Colorado Adoption Project at risk for conduct disorder. AB - Clustering techniques were used to identify a subsample of young adopted and nonadopted children in the Colorado Adoption Project at risk for conduct disorder. Although data from both boys and girls were analyzed, a cluster of girls large enough for subsequent statistical analysis could not be identified; therefore, results are reported for boys only. Identifying measures were selected based on the DSM-III-R diagnostic criteria. Cluster analyses confirmed the existence of a small group of boys who appeared to be significantly at risk. Subsequent parental and teacher ratings of these children verified the stability over time of the classification. The poor conduct group was significantly associated with difficult temperament in infancy, with poor conduct on the part of parents when they were youths, and with high achievement orientation in the home environment. PMID- 1592785 TI - Lower threshold for referral for psychiatric treatment for adopted adolescents. AB - Epidemiological data on a national sample of 3,698 adolescents, of whom 145 were adopted, indicate that adoption significantly increases the likelihood of referral for psychiatric treatment even after controlling for the fact that adoptees display more behavior problems and come from more educated families. This is accounted for by the fact that adoptees are significantly more likely to be referred when they display few problems. Thus, contrary to popular myth and clinical lore, the overrepresentation of young adoptees in clinical settings is not attributable solely to the fact that adoptees are more troubled. Rather, adoptees do display more problems but they are also referred more readily even after controlling for extent of problems. PMID- 1592787 TI - Characteristics of adopted juvenile delinquents. AB - There have been many reports describing the uniqueness of adopted children and adolescents' delinquent behaviors in terms of both their delinquent characteristics and courts' treatment of them. A total of 43 adopted juveniles, 32 extrafamilial (1.0%) and 11 intrafamilial (0.3%) adoptions were initially identified out of 3,280 juvenile delinquents. The adopted subjects were then compared with the demographically matched and offense matched nonadopted subjects. The family variables, such as marital and employment status of parents, were significantly different. However, there were only a few discernible trends, and in general there were no significant differences between the adopted and nonadopted juveniles in terms of their offense characteristics and dispositions. PMID- 1592786 TI - Damaging backgrounds: later adjustment of international adoptees. AB - In this study of 2,148 international adoptees aged 10 to 15 years, the influence of early adverse experiences on later adjustment was examined. It was found that early neglect, abuse, and the number of changes of caretaking environment increased the risk for later maladjustment. The older the age of the child at placement, the greater the probability that the child had been subjected to psychosocial adversities. This association sufficiently explained the greater likelihood of later maladjustment with increasing age of the child at placement. Age at placement, as such, did not contribute to the prediction of later maladjustment, independent of the influence of early adversities. The present study underscores the importance that parents and professionals should obtain reliable and detailed information on the child's background and functioning before adoption. This study also showed that the majority of adopted children, even those with backgrounds known to be damaging, seemed to function quite well according to their parents' reports. PMID- 1592788 TI - Issues of child custody and our moral values in the era of new medical technology. AB - A series of ethical, moral, and legal dilemmas are presented along with the related landmark case law. The definition of motherhood and the types of mothers, such as genetic, gestational, and surrogate, have become a confusing matter, not only for a growing child but for lawmakers and mental health professionals as well. Pregnancy through artificial insemination gives certain rights to women who are not married to the father, even when these women have contracted to surrender the baby after birth. The law has recognized that biological mothers have a potential right to custody or at least visitation. Such a right, however, is not established on behalf of a father whose only relationship with a child is through his genetic component unless a strong emotional bond exists, and the mother is not married to and cohabiting with her husband. The author argues that the principle of "the child's best interest" must prevail in all custody disputes, regardless of who the biological parent is. PMID- 1592789 TI - Oppositional defiant and conduct disorders: issues to be resolved for DSM-IV. AB - Oppositional defiant disorder (ODD) and conduct disorder (CD) are reasonably distinct both in terms of statistical covariation among symptoms and ages of onset. The two disorders are related in similar ways to impairment and family history of antisocial behavior, but the association is stronger for CD than ODD. Virtually all clinic-referred youths with prepubertal onset of CD have retained the symptoms of ODD that emerged at earlier ages. Furthermore, a set of serious antisocial behaviors characteristically emerges at later ages in some youths with CD, suggesting further developmental progression within CD. These findings are consistent with a conceptualization of ODD and CD as developmentally staged, hierarchically organized levels of severity of the same disorder, but two findings argue for distinguishing separate disorders in DSM-IV: (1) many youths with ODD never develop CD, and (2) CD that emerges for the first time in adolescence appears to be independent of ODD. PMID- 1592790 TI - Co-occurrence of conduct disorder and its adult outcomes with depressive and anxiety disorders: a review. AB - Child and adult general population studies of psychiatric disorder were systematically reviewed for data on the co-occurrence of conduct disorder and its adult outcomes with depressive and anxiety disorders. For both sexes, both depressive and anxiety disorders co-occurred with conduct disorder (and its adult outcomes) far more than expected by chance in childhood, adolescence, and adulthood. Most women with conduct disorder and an antisocial adult outcome also developed a depressive or anxiety disorder by early adulthood. For both sexes, increasing severity of antisocial behavior was associated with an increasing risk of an emotional disorder. Age and sex affected the rates of co-occurrence. Possible reasons for this co-occurrence and implications for classification and the nature of conduct disorder are discussed. PMID- 1592791 TI - Ethical dilemmas in child and adolescent consultation psychiatry. AB - Ethical issues in child and adolescent psychiatry consultation arise frequently but seldom are discussed in a public setting. This case of an adolescent victim of a surgical accident illustrates many aspects of consultation psychiatry. The consult question itself, of behavior management, is not unusual, although in this case the question is complicated by the sequelae of trauma, psychosocial chaos, and the staff's angry feelings toward the patient. In addition, potential surgical wrongdoing at the referring hospital brings up the more difficult ethical questions of the consultant's responsibilities, which must be to the patient and his family, as well as to the attending and referring physicians. PMID- 1592792 TI - The board exam debate continued. PMID- 1592793 TI - Diabetic compliance. PMID- 1592794 TI - Desipramine and the EKG. PMID- 1592795 TI - Sympathomimetic-fluoxetine interaction. PMID- 1592796 TI - Hospitals and LOS. PMID- 1592797 TI - ADHD and PDD. PMID- 1592798 TI - Rett syndrome and metabolic disorder. PMID- 1592799 TI - Determinants of extracellular protein secretion in gram-negative bacteria. PMID- 1592800 TI - Localization of cytochromes to the outer membrane of anaerobically grown Shewanella putrefaciens MR-1. AB - In gram-negative bacteria, numerous cell functions, including respiration-linked electron transport, have been ascribed to the cytoplasmic membrane. Gram-negative bacteria which use solid substrates (e.g., oxidized manganese or iron) as terminal electron acceptors for anaerobic respiration are presented with a unique problem: they must somehow establish an electron transport link across the outer membrane between large particulate metal oxides and the electron transport chain in the cytoplasmic membrane. When the metal-reducing bacterium Shewanella putrefaciens MR-1 is grown under anaerobic conditions and membrane fractions are purified from cells lysed by an EDTA-lysozyme-polyoxyethylene cetyl ether (Brij 58) protocol, approximately 80% of its membrane-bound cytochromes are localized in its outer membrane. These outer membrane cytochromes could not be dislodged by treatment with chaotropic agents or by increased concentrations of the nonionic detergent Brij 58, suggesting that they are integral membrane proteins. Cytochrome distribution in cells lysed by a French press protocol confirm the localization of cytochromes to the outer membrane of anaerobically grown cells. This novel cytochrome distribution could play a key role in the anaerobic respiratory capabilities of this bacterium, especially in its ability to mediate manganese and iron reduction. PMID- 1592801 TI - Haloalkaliphilic maltotriose-forming alpha-amylase from the archaebacterium Natronococcus sp. strain Ah-36. AB - A haloalkaliphilic archaebacterium, Natronococcus sp. strain Ah-36, produced extracellularly a maltotriose-forming amylase. The amylase was purified to homogeneity by ethanol precipitation, hydroxylapatite chromatography, hydrophobic chromatography, and gel filtration. The molecular weight of the enzyme was estimated to be 74,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The amylase exhibited maximal activity at pH 8.7 and 55 degrees C in the presence of 2.5 M NaCl. The activity was irreversibly lost at low ionic strength. KCl, RbCl, and CsCl could partially substitute for NaCl at higher concentrations. The amylase was stable in the range of pH 6.0 to 8.6 and up to 50 degrees C in the presence of 2.5 M NaCl. Stabilization of the enzyme by soluble starch was observed in all cases. The enzyme activity was inhibited by the addition of 1 mM ZnCl2 or 1 mM N-bromosuccinimide. The amylase hydrolyzed soluble starch, amylose, amylopectin, and, more slowly, glycogen to produce maltotriose with small amounts of maltose and glucose of an alpha-configuration. Malto oligosaccharides ranging from maltotetraose to maltoheptaose were also hydrolyzed; however, maltotriose and maltose were not hydrolyzed even with a prolonged reaction time. Transferase activity was detected by using maltotetraose or maltopentaose as a substrate. The amylase hydrolyzed gamma-cyclodextrin. alpha Cyclodextrin and beta-cyclodextrin, however, were not hydrolyzed, although these compounds acted as competitive inhibitors to the amylase activity. Amino acid analysis showed that the amylase was characteristically enriched in glutamic acid or glutamine and in glycine. PMID- 1592802 TI - Improved bacterial baby machine: application to Escherichia coli K-12. AB - Exponentially growing derivatives of Escherichia coli K-12 were immobilized onto the surfaces of nitrocellulose membrane filters which had been coated with poly-D lysine. The cells attached firmly to the surfaces, and when flushed with culture medium, the immobilized cells continued to divide and newborn cells were released into the effluent. Cell cycle parameters were examined with the technique, and it was found that K-12 derivatives possessed differing values for interdivision times, C, D, and average cell sizes when grown in the same culture media. It was also found that the cells released from immobilized populations of one culture consisted of two predominant size classes: newborn cells of unit size with single nucleoids and newborn cells of double this unit size. The results demonstrated that K-12 derivatives can be used in the baby machine culture technique to examine all aspects of the cell cycle of this organism. Furthermore, the yield of newborn cells was about fivefold greater than that obtained previously with cultures of strain B/r immobilized onto uncoated membranes. PMID- 1592803 TI - Chitinases of Streptomyces olivaceoviridis and significance of processing for multiplicity. AB - Five extracellular chitinases of 20.5, 30, 47, 70, and 92 kDa purified from the culture filtrate of Streptomyces olivaceoviridis ATCC 11238 differed in their sequences at the amino termini of the protein chains. In the native state, the chitinases were found to be resistant to proteolysis by trypsin, papain, and Staphylococcus aureus V8 protease. The latter produced several fragments of identical molecular mass from chitinases denaturated with sodium dodecyl sulfate. Five proteases were detected in the protein concentrate from the culture filtrate, and two of them showing ability to cleave chitinases in the native state were purified. One, a protease of 42 kDa, released a 30-kDa protein from the 70-kDa chitinase that reacts with anti-30 kDa chitinase antibodies; the other, a protease of 29 kDa, split the 30-kDa chitinase into 20.5-, 18-, and 16 kDa fragments. From these results, it was deduced that the 70-kDa chitinase is the precursor protein of the 30- and 20.5-kDa chitinases. PMID- 1592804 TI - Anaerobic induction of pyruvate formate-lyase gene expression is mediated by the ArcA and FNR proteins. AB - The pyruvate formate-lyase (pfl) gene of Escherichia coli is transcribed from seven promoters which are coordinately induced 12- to 15-fold by anaerobiosis. The FNR protein plays a major role in the anaerobic control of this system. A mutation in the fnr gene, however, only reduces anaerobic induction fivefold, indicating that FNR is not the only factor involved in the anaerobic activation process (Sawers and Bock, J. Bacteriol. 171:2485-2498, 1989). The residual anaerobic induction could be shown to be imparted by the transcriptional regulator ArcA; an arcA fnr double mutant was incapable of inducing pfl transcription anaerobically. A mutant strain unable to synthesize the membrane associated histidine kinase (ArcB) that has been proposed to activate ArcA showed the same phenotype as an arcA mutant strain, indicating that a functional ArcB protein is also required for wild-type, anaerobic pfl transcriptional activation. Nuclease S1 analysis revealed that an arcA mutation abolished anaerobic transcription from promoter 7 and reduced expression from promoter 6 but did not affect transcription from promoters 1 to 5. On the other hand, an fnr mutation prevented anaerobic expression from promoters 6 and 7 and reduced transcription from promoters 1 to 5. These data indicate that both ArcA and FNR are essential for anaerobic activation of promoter 7 transcription, which suggests functional interaction between these proteins. PMID- 1592805 TI - Plant and environmental sensory signals control the expression of hrp genes in Pseudomonas syringae pv. phaseolicola. AB - The hrp genes of Pseudomonas syringae pv. phaseolicola control the development of primary disease symptoms in bean plants and the elicitation of the hypersensitive response in resistant plants. We examined the expression of the seven operons located in the 22-kb hrp cluster (L. G. Rahme, M. N. Mindrinos, and N. J. Panopoulos, J. Bacteriol. 173:575-586, 1991) in planta and in vitro under different physiological and nutritional conditions by using chromosomally located hrp::inaZ reporter fusions. We show that (i) a plant signal(s) is specifically required for the induction of the seven hrp operons, during both compatible and incompatible interactions; (ii) hrpL and hrpRS are regulated by different mechanisms in planta and in vitro; and (iii) expression of individual hrp loci is differentially affected by pH, osmotic strength, and type of carbon source: hrpAB, hrpC, and hrpD were downregulated similarly by osmolarity, pH, and certain carbon sources; hrpE expression was affected strongly by pH and carbon substrate and slightly by osmolarity; and hrpF was not substantially affected by any of these factors. These findings suggest complex signaling mechanisms taking place during plant-pathogen interactions. PMID- 1592806 TI - Transcription in vivo and in vitro of the histone-encoding gene hmfB from the hyperthermophilic archaeon Methanothermus fervidus. AB - Immediately upstream of the hmfB gene, in a DNA fragment cloned from Methanothermus fervidus, are two identical tandemly repeated copies of a 73-bp sequence that contain the sequence 5'TTTATATA, which conforms precisely to the consensus TATA box element proposed for methanogen promoters. By using this duplicated region as the template DNA and a cell-free transcription system derived from Methanococcus thermolithotrophicus, transcription in vitro was found to initiate at two identical sites 73 bp apart, each 25 bp downstream from a TATA box, thus providing strong evidence for the functional conservation of this transcriptional signal in two phylogenetically very diverse methanogens. Transcription of the hmfB gene in vivo in M. fervidus was found to occur at only one of these sites, and consistent with this observation, recloning and sequencing of this intergenic region after its amplification by the polymerase chain reaction demonstrated that the genome of M. fervidus contains only one copy of the 73-bp sequence upstream of the hmfB gene. Since the second copy of the 73 bp sequence, presumably generated artifactually during the original hmfB cloning, functioned equally well as a promoter in the M. thermolithotrophicus transcription system, all information needed by the heterologous RNA polymerase to initiate transcription accurately in vitro must be present within this sequence. The hmfB gene encodes HMf-2, one of the two subunits of HMf, an abundant DNA binding protein in M. fervidus which binds to DNA molecules in vitro, forming nucleosomelike structures. Cell-free transcription was inhibited by adding HMf or eucaryotic core histones at protein-to-DNA mass ratios of 0.3:1 and 1:1, respectively, whereas the archael histonelike protein HTa from Thermoplasma acidophilum inhibited transcription in vitro only at much higher protein-to-DNA mass ratios and the bacterial histonelike protein HU from Escherichia coli had no detectable effect on transcription. PMID- 1592807 TI - celA from Bacillus lautus PL236 encodes a novel cellulose-binding endo-beta-1,4 glucanase. AB - celA from the cellulolytic bacterium Bacillus lautus PL236 encodes EG-A, an endo beta-1,4-glucanase. An open reading frame of 2,100 bp preceded by a ribosome binding site encodes a protein with a molecular mass of 76,863 Da with a typical signal sequence. The NH2-terminal active domain of EG-A is not homologous to any reported cellulase or xylanase and may represent a new family of such enzymes. A 150-amino-acid COOH-terminal peptide is homologous to noncatalytic domains in several other cellulases (A. Meinke, N.R. Gilkes, D.G. Kilburn, R.C. Miller, Jr., and R.A.J. Warren, J. Bacteriol. 173:7126-7135, 1991). Upstream of celA, a partial open reading frame encodes a 145-amino-acid peptide which also belongs to the family mentioned. Zymogram analysis of extracts from Escherichia coli and supernatants of Bacillus subtilis and B. megaterium, including protease-deficient mutants thereof, which express celA, revealed two active proteins, EG-A-L and EG A-S, with Mrs of 74,000 and 57,000, respectively. The proportion of EG-A-L to EG A-S depends on the extracellular proteolytic activity of the host organism, indicating that EG-A-S arises from posttranslational proteolytic modification of EG-A-L. Since EG-A-S has an NH2 terminus corresponding to the predicted NH2 terminal sequence of EG-A, processing appears to take place between the catalytic and noncatalytic domains described. EG-A-L and EG-A-S were purified to homogeneity and shown to have almost identical characteristics with respect to activity against soluble substrates and pH and temperature dependency. EG-A-L binds strongly to cellulose, in contrast to EG-A-S, and has higher activity against insoluble substrates than the latter. We conclude that the COOH-terminal 17,000-Mr peptide of EG-A-L constitutes a cellulose-binding domain. PMID- 1592808 TI - Heterogeneity and regulation of manganese peroxidases from Phanerochaete chrysosporium. AB - Lignin and Mn peroxidases are two families of isozymes produced by the lignin degrading fungus Phanerochaete chrysosporium under nutrient nitrogen or carbon limitation. We purified to homogeneity the three major Mn peroxidase isozymes, H3 (pI = 4.9), H4 (pI = 4.5), and H5 (pI = 4.2). Amino-terminal sequencing of these isozymes demonstrates that they are encoded by different genes. We also analyzed the regulation of these isozymes in carbon- and nitrogen-limited cultures and found not only that the lignin and Mn peroxidases are differentially regulated but also that differential regulation occurs within the Mn peroxidase isozyme family. The isozyme profile and the time at which each isozyme appears in secondary metabolism differ in both nitrogen- and carbon-limited cultures. Each isozyme also responded differently to the addition of a putative inducer, divalent Mn. The stability of the Mn peroxidases in carbon- and nitrogen-limited cultures was also characterized after cycloheximide addition. The Mn peroxidases are more stable in carbon-limited cultures than in nitrogen-limited cultures. They are also more stable than the lignin peroxidases. These data collectively suggest that the Mn peroxidase isozymes serve different functions in lignin biodegradation. PMID- 1592809 TI - Membrane intermediates in the peptidoglycan metabolism of Escherichia coli: possible roles of PBP 1b and PBP 3. AB - The two membrane precursors (pentapeptide lipids I and II) of peptidoglycan are present in Escherichia coli at cell copy numbers no higher than 700 and 2,000 respectively. Conditions were determined for an optimal accumulation of pentapeptide lipid II from UDP-MurNAc-pentapeptide in a cell-free system and for its isolation and purification. When UDP-MurNAc-tripeptide was used in the accumulation reaction, tripeptide lipid II was formed, and it was isolated and purified. Both lipids II were compared as substrates in the in vitro polymerization by transglycosylation assayed with PBP 1b or PBP 3. With PBP 1b, tripeptide lipid II was used as efficiently as pentapeptide lipid II. It should be stressed that the in vitro PBP 1b activity accounts for at best to 2 to 3% of the in vivo synthesis. With PBP 3, no polymerization was observed with either substrate. Furthermore, tripeptide lipid II was detected in D-cycloserine-treated cells, and its possible in vivo use in peptidoglycan formation is discussed. In particular, it is speculated that the transglycosylase activity of PBP 1b could be coupled with the transpeptidase activity of PBP 3, using mainly tripeptide lipid II as precursor. PMID- 1592810 TI - High information conservation implies that at least three proteins bind independently to F plasmid incD repeats. AB - The 12 incD repeats in the F plasmid each contain about 60 bits of information, which is three times the amount of conservation that a single protein would need to distinguish the repeats from the rest of the Escherichia coli genome. This is the first reported discovery of a case of threefold excess information, and it implies that at least three proteins bind independently to the repeats. In support of this observation, other workers have shown that three polypeptides bind to this region, but only one, SopB, is known to bind independently of other factors. Identification of the other two proteins should help us to understand the mechanism of plasmid partitioning during cell division. PMID- 1592811 TI - Sin, a stage-specific repressor of cellular differentiation. AB - Sin is a Bacillus subtilis DNA-binding protein which is essential for competence, motility, and autolysin production but also, if expressed on a multicopy plasmid, is inhibitory to sporulation and alkaline protease synthesis. We have now examined the physiological role of Sin in sporulation and found that this protein specifically represses three stage II sporulation genes (spoIIA, spoIIE, and spoIIG) but not the earlier-acting stage 0 sporulation genes. sin loss-of function mutations cause higher expression of stage II genes and result in a higher frequency of sporulation, in general. Sin binds to the upstream promoter region of spoIIA in vitro and may thus gate entry into sporulation by directly repressing the transcription of stage II genes. In vivo levels of Sin increase rather than decrease at the time of stage II gene induction, suggesting that posttranslational modification may play a role in downregulation of negative Sin function. PMID- 1592812 TI - Roles of rpoD, spoIIF, spoIIJ, spoIIN, and sin in regulation of Bacillus subtilis stage II sporulation-specific transcription. AB - Bacillus subtilis strains containing defects in the sporulation gene spoIIF (kinA), spoIIJ (kinA), or spoIIN (ftsA) cannot transcribe the sigma E-dependent gene spoIID. Results presented here and by other workers demonstrate that the spoIIF, spoIIJ, and spoIIN gene products control spoIID transcription indirectly by coordinating the induction of the spoIIGAB, spoIIE, and spoIIAC operons, which are required for sigma E synthesis and processing. Sporulation competence and spoIIGAB, spoIIE, and spoIIAC transcription were restored in spoIIF, spoIIJ, and spoIIN mutants by introduction of crsA47, a mutation in the major vegetative sigma factor sigma A. crsA mutations are known to restore sporulation in certain spo0 mutants. crsA suppression of kinA and ftsA mutations was achieved through inhibition of the transcription of sin, a gene involved in the selection between several post-exponential-phase cell states. A deletion of sin restored sporulation competence in spoIIF, spoIIJ, or spoIIN mutant strains. A sin deletion was also able to restore sporulation competence in the crsA suppressible stage 0 mutant spo0K141. PMID- 1592813 TI - Molecular evolutionary genetics of the cattle-adapted serovar Salmonella dublin. AB - An electrophoretic analysis of allelic variation at 24 enzyme loci among 170 isolates of the serovar Salmonella dublin (serotype 1,9,12[Vi]:g,p:-) identified three electrophoretic types (Du 1, Du 3, and Du 4), marking three closely related clones, one of which (Du 1) is globally distributed and was represented by 95% of the randomly selected isolates. All but 1 of 114 nonmotile isolates of serotype 1,9,12:-:- recovered from cattle and swine in the United States were genotypically Du 1. The virulence capsular polysaccharide (Vi antigen) is confined to clone Du 3, which apparently is limited in distribution to France and Great Britain. For all 29 isolates of Du 3, positive signals were detected when genomic DNA was hybridized with a probe specific for the ViaB region, which contains the structurally determinant genes for the Vi antigen; and 23 of these isolates had been serologically typed as Vi positive. In contrast, all 30 isolates of Du 1 tested with the ViaB probe were negative. These findings strongly suggest that the ViaB genes were recently acquired by S. dublin via horizontal transfer and additive recombination. The clones of S. dublin are closely similar to the globally predominant clone (En 1) of Salmonella enteritidis (serotype 1,9,12:g,m:-) in both multilocus enzyme genotype and nucleotide sequence of the fliC gene encoding phase 1 flagellin. Comparative sequencing of fliC has revealed the molecular genetic basis for expression of the p and m flagellar epitopes by which these serovars are distinguished in the Kauffmann-White serological scheme of classification. PMID- 1592814 TI - Reversible inactivation and characterization of purified inactivated form I ribulose 1,5-bisphosphate carboxylase/oxygenase of Rhodobacter sphaeroides. AB - Form I ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO) from Rhodobacter sphaeroides is inactivated upon the addition of organic acids to photolithoautotrophically grown cultures. Activity recovers after the dissipation of the organic acid from the culture. The inactivation process depends on both the concentration of the organic compound and the nitrogen status of the cells. The inactivated RubisCO has been purified and was shown to exhibit mobility on both nondenaturing and sodium dodecyl sulfate gels different from that of the active enzyme prepared from cells not treated with organic acids. However, the Michaelis constants for ribulose 1,5-bisphosphate and CO2 or O2 were not dramatically altered. Purified inactivated RubisCO could be activated in vitro by increasing the temperature or the levels of Mg(II), and this activation was accompanied by changes in the electrophoretic mobility of the protein. When foreign bacterial RubisCO genes were expressed in an R. sphaeroides host strain lacking the ability to synthesize endogenous RubisCO, only slight inactivation of RubisCO activity was attained. PMID- 1592815 TI - Waxy Chlamydomonas reinhardtii: monocellular algal mutants defective in amylose biosynthesis and granule-bound starch synthase activity accumulate a structurally modified amylopectin. AB - Amylose-defective mutants were selected after UV mutagenesis of Chlamydomonas reinhardtii cells. Two recessive nuclear alleles of the ST-2 gene led to the disappearance not only of amylose but also of a fraction of the amylopectin. Granule-bound starch synthase activities were markedly reduced in strains carrying either st-2-1 or st-2-2, as is the case for amylose-deficient (waxy) endosperm mutants of higher plants. The main 76-kDa protein associated with the starch granule was either missing or greatly diminished in both mutants, while st 2-1-carrying strains displayed a novel 56-kDa major protein. Methylation and nuclear magnetic resonance analysis of wild-type algal storage polysaccharide revealed a structure identical to that of higher-plant starch, while amylose defective mutants retained a modified amylopectin fraction. We thus propose that the waxy gene product conditions not only the synthesis of amylose from endosperm storage tissue in higher-plant amyloplasts but also that of amylose and a fraction of amylopectin in all starch-accumulating plastids. The nature of the ST 2 (waxy) gene product with respect to the granule-bound starch synthase activities is discussed. PMID- 1592817 TI - Carboxylation of phenylphosphate by phenol carboxylase, an enzyme system of anaerobic phenol metabolism. AB - Several lines of evidence indicate that the first step in the anaerobic metabolism of phenol is phenol carboxylation to 4-hydroxybenzoate; this reaction is considered a biological Kolbe-Schmitt carboxylation. A phenol carboxylase system was characterized by using a denitrifying Pseudomonas strain, K 172, which catalyzes an isotope exchange between 14CO2 and the carboxyl group of 4 hydroxybenzoate. The enzymatic isotope exchange activity (100 nmol min-1 mg-1 of protein) requires Mn2+ and K+. We show that this system also catalyzes the carboxylation of phenylphosphate (the phosphoric acid monophenyl ester) to 4 hydroxybenzoate and phosphate. The specific activity of phenylphosphate carboxylation at the optimal pH of 6.5 is 12 nmol of CO2 fixed min-1 mg-1 of protein. Phenylphosphate cannot be replaced by Mg(2+)-ATP and phenol. The carboxylase activity requires Mn2+ but, in contrast to the isotope exchange activity, does not require K+. The apparent Km values are 1.5 mM dissolved CO2 and 0.2 mM phenylphosphate. Several convenient assays for phenylophosphate carboxylation are described. The isotope exchange reaction and the net carboxylation reaction are catalyzed by the same oxygen-sensitive enzyme, which has a half-life in an air-saturated solution of less than 1 min. Both activities cochromatographed with a protein with a Mr of 280,000, and both activities were induced only after anaerobic growth on phenol. The carboxylation of phenylphosphate suggests that phenylphosphate itself is the physiological CO2 acceptor molecular of this novel CO2 fixation reaction. Alternatively, phenylphosphate could simulate the unknown natural precursor. It is suggested that the formation of an enzyme-bound phenolate anion from the activated phenolic compound is the rate-determining step in the carboxylation reaction. PMID- 1592816 TI - Anaerobic degradation of 2-aminobenzoic acid (anthranilic acid) via benzoyl coenzyme A (CoA) and cyclohex-1-enecarboxyl-CoA in a denitrifying bacterium. AB - The enzymes catalyzing the initial reactions in the anaerobic degradation of 2 aminobenzoic acid (anthranilic acid) were studied with a denitrifying Pseudomonas sp. anaerobically grown with 2-aminobenzoate and nitrate as the sole carbon and energy sources. Cells grown on 2-aminobenzoate are simultaneously adapted to growth with benzoate, whereas cells grown on benzoate degrade 2-aminobenzoate several times less efficiently than benzoate. Evidence for a new reductive pathway of aromatic metabolism and for four enzymes catalyzing the initial steps is presented. The organism contains 2-aminobenzoate-coenzyme A ligase (2 aminobenzoate-CoA ligase), which forms 2-aminobenzoyl-CoA. 2-Aminobenzoyl-CoA is then reductively deaminated to benzoyl-CoA by an oxygen-sensitive enzyme, 2 aminobenzoyl-CoA reductase (deaminating), which requires a low potential reductant [Ti(III)]. The specific activity is 15 nmol of 2-aminobenzoyl-CoA reduced min-1 mg-1 of protein at an optimal pH of 7. The two enzymes are induced by the substrate under anaerobic conditions only. Benzoyl-CoA is further converted in vitro by reduction with Ti(III) to six products; the same products are formed when benzoyl-CoA or 2-aminobenzoyl-CoA is incubated under reducing conditions. Two of them were identified preliminarily. One product is cyclohex-1 enecarboxyl-CoA, the other is trans-2-hydroxycyclohexane-carboxyl-CoA. The complex transformation of benzoyl-CoA is ascribed to at least two enzymes, benzoyl-CoA reductase (aromatic ring reducing) and cyclohex-1-enecarboxyl-CoA hydratase. The reduction of benzoyl-CoA to alicyclic compounds is catalyzed by extracts from cells grown anaerobically on either 2-aminobenzoate or benzoate at almost the same rate (10 to 15 nmol min-1 mg-1 of protein). In contrast, extracts from cells grown anaerobically on acetate or grown aerobically on benzoate or 2 aminobenzoate are inactive. This suggests a sequential induction of the enzymes. PMID- 1592818 TI - The Escherichia coli K-12 cyn operon is positively regulated by a member of the lysR family. AB - A regulatory gene, cynR, was found to be located next to the cyn operon but transcribed in the opposite direction. cynR encodes a positive regulatory protein that controls the cyn operon as well as its own synthesis. Positive regulation of the cyn operon requires cyanate and the cynR protein, but the negative autoregulation of the cynR gene appears to be independent of cyanate. The predicted amino acid sequence of the cynR protein derived from the DNA sequence was found to have significant homology to the predicted amino acid sequence of the lysR family of regulatory proteins. PMID- 1592819 TI - Sequence and transcriptional analysis of the Streptomyces glaucescens tcmAR tetracenomycin C resistance and repressor gene loci. AB - Sequence analysis of the tcmA tetracenomycin C resistance gene from Streptomyces glaucescens GLA.O (ETH 22794) identifies one large open reading frame whose deduced product has sequence similarity to the mmr methylenomycin resistance gene from Streptomyces coelicolor, the Streptomyces rimosus tet347 (otrB) tetracycline resistance gene, and the atr1 aminotriazole resistance gene from Saccharomyces cerevisiae. These genes are thought to encode proteins that act as metabolite export pumps powered by transmembrane electrochemical gradients. A divergently transcribed gene, tcmR, is located in the region upstream of tcmA. The deduced product of tcmR resembles the repressor proteins encoded by tetR regulatory genes from Escherichia coli and the actII-orf1 gene from S. coelicolor. Transcriptional analysis of tcmA and tcmR indicates that these genes have back-to-back and overlapping promoter regions. PMID- 1592820 TI - The Streptomyces glaucescens TcmR protein represses transcription of the divergently oriented tcmR and tcmA genes by binding to an intergenic operator region. AB - Preliminary evidence has been presented by Guilfoile and Hutchinson (J. Bacteriol. 174:3651-3658, 1992) suggesting that the Streptomyces glaucescens TcmR protein is a transcriptional repressor. Here, we extend that work by showing that transcription of the S. glaucescens tcmA gene is inducible by tetracenomycin C and that inactivation of the tcmR gene results in constitutive transcription of the tcmA gene. Gel retardation studies show that the TcmR protein binds to the tcmA-tcmR intergenic region in vitro and that this binding is inhibited by tetracenomycin C. Footprinting experiments demonstrate that the TcmR protein binds to an operator region that encompasses both the tcmA and the tcmR promoters. This genetic and biochemical evidence strongly supports the model of the TcmR protein acting as a repressor in inhibiting transcription of both the tcmA and the tcmR genes, in much the same way that TetR from Tn10 inhibits transcription of tetA and tetR. PMID- 1592821 TI - Mutational analysis reveals functional similarity between NARX, a nitrate sensor in Escherichia coli K-12, and the methyl-accepting chemotaxis proteins. AB - During anaerobic growth, nitrate induces synthesis of the anaerobic respiratory enzymes formate dehydrogenase-N and nitrate reductase. This induction is mediated by a transcription activator, the narL gene product. The narX gene product may be involved in sensing nitrate and phosphorylating NARL. We isolated narX mutants, designated narX*, that caused nitrate-independent expression of the formate dehydrogenase-N and nitrate reductase structural genes. We used lambda narX specialized transducing phage to genetically analyze these lesions in single copy. Two previously isolated narX* mutations, narX32 and narX71, were also constructed by site-specific mutagenesis. We found that each of these alleles caused nitrate-independent synthesis of formate dehydrogenase-N and nitrate reductase, and each was recessive to narX+. The narX* mutations lie in a region of similarity with the methyl-accepting chemotaxis protein Tsr. We suggest that the narX* proteins have lost a transmembrane signalling function such that phosphoprotein phosphatase activity is reduced relative to protein kinase activity. PMID- 1592822 TI - Activation of Bacillus subtilis transcription factor sigma B by a regulatory pathway responsive to stationary-phase signals. AB - Alternative transcription factor sigma B of Bacillus subtilis controls a stationary-phase regulon induced under growth conditions that do not favor sporulation. Little is known about the metabolic signals and protein factors regulating the activity of sigma B. The operon containing the sigma B structural gene has the gene order orfV-orfW-sigB-rsbX, and operon expression is autoregulated positively by sigma B and negatively by the rsbX product (rsbX = regulator of sigma B). To establish the roles of the orfV and orfW products, orfV and orfW null and missense mutations were constructed and tested for their effects on expression of the sigma B-dependent genes ctc and csbA. These mutations were tested in two contexts: in the first, the sigB operon was under control of its wild-type, sigma B-dependent promoter, and in the second, the sigB operon promoter was replaced by the inducible Pspac promoter. The principal findings are that (i) the orfV (now called rsbV) product is a positive regulator of sigma B-dependent gene expression; (ii) the orfW (now called rsbW) product is a negative regultor of such expression; (iii) sigma B is inactive during logarithmic growth unless the rsbW product is absent; (iv) the rsbX, rsbV, and rsbW products have a hierarchical order of action; and (v) both the rsbV and rsbW products appear to regulate sigma B activity posttranslationally. There are likely to be at least two routes by which information can enter the system to regulate sigma B: via the rsbX product, and via the rsbV and rsbW products. PMID- 1592824 TI - Significance of NADP/NAD glutamate dehydrogenase ratio in the dimorphic behavior of Benjaminiella poitrasii and its morphological mutants. AB - Studies on the levels of glutamate dehydrogenase (GDH), glutamine synthetase, and glutamate synthase were carried out as a function of temperature, nutritional conditions, and the morphological (yeast or mycelium) form of Benjaminiella poitrasii. Since both NAD- and NADP-dependent GDH activities were found in B. poitrasii, the quantitative relation between these two enzymes expressed as the NADP-GDH/NAD-GDH activity ratio (GDH ratio) was studied to evaluate its possible role in the morphogenesis. In the yeast-to-mycelium transition, a decrease in the GDH ratio occurred (between 1 and 2 h) and germ tube formation could be observed only at 3 h. Under similar sets of experimental conditions, exogenous addition 1.0 mM of alpha-ketoglutarate delayed germ tube emergence (4 h) compared with the control. On the other hand, in the presence of 1.0 mM glutamate an earlier onset of the germ tube formation was noted. The morphological (monomorphic) mutants, Y 2 and Y-5, showed a high GDH ratio and maintained the yeast morphology. PMID- 1592823 TI - DNA sequence analysis of the dnaK gene of Escherichia coli B and of two dnaK genes carrying the temperature-sensitive mutations dnaK7(Ts) and dnaK756(Ts). AB - The DNA sequence of the dnaK gene of Escherichia coli was analyzed. The nucleotide sequence of the wild-type dnaK gene of E. coli B differed from that of E. coli K-12 in 15 bp, none of which altered the amino acid sequence. Two temperature-sensitive dnaK mutations were examined by cloning and sequence analyses. Results showed that one dnaK mutation, dnaK7(Ts), was a one-base substitution of T for C at nucleotide position 448 in the open reading frame yielding an amber nonsense codon. The other mutation, dnaK756(Ts), consisted of base substitutions (A for G) at three nucleotide positions, 95, 1364, and 1403, in the open reading frame resulting in an aspartic acid codon in place of a glycine codon. PMID- 1592825 TI - Group B streptococcal opacity variants. AB - Colony opacity variants were detected for type III group B streptococci (GBS). Transparent colonies predominate in the parent GBS, with occasional colonies having opaque portions. Two stable opaque variants (1.1 and 1.5) were compared with three transparent clones (1.2, 1.3, and 1.4). All grew well on blood agar and on GC medium, but variant 1.1 failed to grow on Todd-Hewitt medium. Scanning and transmission electron microscopy demonstrated that colony opacity correlated with bacterial aggregation status, with opaque variants forming longer and more organized chains. Opaque-transparent switches were observed in both directions for most variants, with transparent to opaque noted most frequently, but 1.5 did not switch at all. Switching of the opacity phenotype was observed both in vitro and in neonatal mice. Relationships between colony opacity and several cell surface phenomena were explored. (i) Opaque variant 1.1 had two surface proteins (46 and 75 kDa) that were either unique or greatly overexpressed. (ii) Variant 1.1 was deficient in type III polysaccharide, while 1.5 lacked group B antigen. Diminished capsular polysaccharide of variant 1.1 was reflected in reduced negative electrophoretic mobility and in increased buoyant density. (iii) Transparent variant colonies growing closest to a penicillin disk were opaque, but colonial variants did not differ in their sensitivity to penicillin. These data indicate that GBS can exist in both opaque and transparent forms, with opaque appearance occurring by multiple routes. Opaque variants grow poorly on Todd-Hewitt medium generally used for isolation of GBS, so any possible relationships between opacity variation and pathogenesis of GBS infection are unknown. PMID- 1592826 TI - Physical maps of the genomes of three Bacillus cereus strains. AB - NotI restriction maps of the chromosomes from Bacillus cereus ATCC 10876, ATCC 11778, and the B. cereus type strain ATCC 14579 have been established and compared with the previously established map of B. cereus ATCC 10987. Between 10 and 14 NotI fragments were observed, ranging from 15 to 1,300 kb, in digests of DNA from the various strains. The sizes of the genomes varied between 5.4 and 6.3 Mb. The maps were constructed by hybridization of 42 random probes, prepared from B. cereus ATCC 10987 libraries, to fragments from partial and complete NotI digests, separated by pulsed-field gel electrophoresis. Nine probes were specific for ATCC 10987 only. Probes for five B. subtilis and five B. cereus genes were also used. The NotI restriction fragment patterns of the four strains were strikingly different. PMID- 1592827 TI - Physical map of the linear chromosome of the bacterium Borrelia burgdorferi 212, a causative agent of Lyme disease, and localization of rRNA genes. AB - The spirochete Borrelia burgdorferi, which causes Lyme disease, and other members of the Borrelia genus are unique among characterized bacteria in having a linear chromosome. A restriction map of the chromosome of B. burgdorferi 212 was constructed by making extensive use of digestions in agarose blocks of restriction endonuclease fragments or chromosomal DNA that had been purified by pulsed-field gel electrophoresis. A total of 47 digestion sites for the enzymes SgrAI, SacII, MluI, BssHII, EagI, SmaI, NaeI, and ApaI were located. In most regions of the map, the gap between sites is 50 kbp or less, and 122 kbp is the largest distance between adjacent sites. The mapping data were consistent with previous conclusions that the B. burgdorferi chromosome is linear. The total size of the B. burgdorferi 212 chromosome was determined to be 946 kbp from the sums of the sizes of SacII, MluI, BssHII, and SmaI fragments, making it one of the smallest known bacterial chromosomes. The rRNA genes were found to be located near the center of the chromosome. One copy of the 16S rRNA gene (rrs) and two copies of the 23S rRNA gene (designated rrlA and rrlB), the latter pair in a tandem repeat, were detected. This particular complement of these two genes has not been reported for another bacterium. PMID- 1592828 TI - Transcriptional and posttranscriptional components of psbA response to high light intensity in Synechococcus sp. strain PCC 7942. AB - The psbA genes, which encode the D1 protein of photosystem II, constitute a multigene family in the cyanobacterium Synechococcus sp. strain PCC 7942. Levels of messages from the three psbA genes change rapidly when cells are shifted from low-light to high-light conditions: the psbAI message level drops, whereas psbAII and psbAIII message levels increase dramatically. We examined the potential contributions of transcriptional and posttranscriptional processes in these high light responses by subjecting cells that had been grown in a turbidostat at a standard light intensity (130 microeinsteins [microE] m-2 s-1) to either the same or a higher light intensity (500 microE m-2 s-1) in the presence or absence of rifampin. Northern (RNA blot) analysis of RNA isolated from cells subjected to high light showed that the increases in psbAII and psbAIII transcripts were blocked by rifampin. This suggests a transcriptional induction of these genes at high light intensities. Increased mRNA stability does not contribute to their accumulation in high-light conditions, since their half-life values did not increase relative to the half-lives measured at the standard light intensity. The rate of disappearance of the psbAI transcript in cells shifted to high light was diminished when either transcription or translation was blocked by rifampin or chloramphenicol, suggesting that accelerated degradation of the message requires de novo synthesis of a protein factor. When rifampin was added 10 min after the shift to high light intensity rather than before the shift, psbAI and psbAIII messages, but not the psbAII message, decayed at a faster rate. Susceptibility of the psbAIII transcript to the high-light-induced factor was also demonstrated by addition of chloramphenicol prior to the shaft to high light. psbAIII transcript levels went up more than twofold higher in chloramphenicol-treated cells than in untreated cells, whereas psbAII transcript levels were affected by the inhibitor. These experiments provide evidence that either new or increased synthesis of a degradation factor which affects a subset of Synechococcus transcripts occurs in cells subjected to high light intensity. PMID- 1592829 TI - Proline biosynthesis in Saccharomyces cerevisiae: analysis of the PRO3 gene, which encodes delta 1-pyrroline-5-carboxylate reductase. AB - The PRO3 gene of Saccharomyces cerevisiae encodes the 286-amino-acid protein delta 1-pyrroline-5-carboxylate reductase [L-proline:NAD(P+) 5-oxidoreductase; EC 1.5.1.2], which catalyzes the final step in proline biosynthesis. The protein has substantial similarity to the pyrroline carboxylate reductases of diverse bacterial species, soybean, and humans. Using RNA hybridization and measurements of enzyme activity, we have determined that the expression of the PRO3 gene appears to be constitutive. It is not repressed by the pathway end product (proline), induced by the initial substrate (glutamate), or regulated by the general control system. Its expression is not detectably altered when cells are grown in a wide range of nitrogen sources or when glycerol and ethanol replace glucose as the carbon source. The possibility that this enzyme has other functions in addition to proline biosynthesis is discussed. PMID- 1592831 TI - Mutations in the precursor region of a Bacillus subtilis sporulation sigma factor. AB - Transcription from some sporulation-specific promoters of Bacillus subtilis is dependent on synthesis of pro-sigma E and its conversion to sigma E by proteolysis. Certain mutations in the precursor region of sigE, the gene encoding pro-sigma E, apparently allow the mutant sigE products to be active as sigma factors without being proteolysed in the normal way. PMID- 1592830 TI - Regulation of Aspergillus nidulans penicillin biosynthesis and penicillin biosynthesis genes acvA and ipnA by glucose. AB - Expression of the Aspergillus nidulans penicillin biosynthesis genes acvA and ipnA, encoding delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine synthetase and isopenicillin N synthetase, respectively, was analyzed. The intergenic region carrying the divergently oriented promoters was fused in frame in both orientations to Escherichia coli lacZ and E. coli uidA reporter genes. Each construct permits simultaneous expression studies of both genes. Transformants of A. nidulans carrying a single copy of either plasmid integrated at the chromosomal argB locus were selected for further investigations. Expression of both genes was directed by the 872-bp intergenic region. ipnA- and acvA-derived gene fusions were expressed from this region at different levels. ipnA had significantly higher expression than did acvA. Glucose specifically reduced the production of penicillin and significantly repressed the expression of ipnA but not of acvA gene fusions. The specific activities of isopenicillin N synthetase, the gene product of ipnA, and acyl coenzyme A:6-aminopenicillanic acid acyltransferase were also reduced in glucose-grown cultures. PMID- 1592832 TI - Purification and characterization of the acyl carrier protein of the Streptomyces glaucescens tetracenomycin C polyketide synthase. AB - The acyl carrier protein (ACP) of the tetracenomycin C polyketide synthase, encoded by the tcmM gene, has been expressed in both Streptomyces glaucescens and Escherichia coli and purified to homogeneity. Expression of the tcmM gene in E. coli results mainly in the TcmM apo-ACP, whereas expression in S. glaucescens yields solely the holo-ACP. The purified holo-TcmM is active in a malonyl coenzyme A:ACP transacylase assay and is labeled by radioactive beta-alanine, confirming that it carries a 4'-phosphopantetheine prosthetic group. PMID- 1592833 TI - Locations of genes encoding alkyl hydroperoxide reductase on the physical map of the Escherichia coli K-12 genome. PMID- 1592834 TI - Locations of the envCD genes on the physical map of the Escherichia coli chromosome. PMID- 1592835 TI - Location of the hisGDCBHAFI operon on the physical map of Escherichia coli. PMID- 1592836 TI - Physical map location and transcriptional orientation of the tyrR gene of Escherichia coli K-12. PMID- 1592837 TI - Physical map location of the argFGH operon of Escherichia coli. PMID- 1592838 TI - Localization of the entire fec region at 97.3 minutes on the Escherichia coli K 12 chromosome. PMID- 1592840 TI - Methylphenidate as a treatment for depression in acquired immunodeficiency syndrome: an n-of-1 trial. AB - BACKGROUND: Uncontrolled studies report that methylphenidate effectively treats depression in patients with acquired immunodeficiency syndrome (AIDS). Other studies report that methylphenidate improves cognition in patients with dementia stemming from human immunodeficiency virus (HIV). We performed a double-blind, placebo-controlled n-of-1 trial to learn whether methylphenidate was an effective treatment for depression in an outpatient with mild HIV dementia. METHOD: The patient received either placebo or drug in a double-blinded fashion in increasing doses in each of three 2-week phases (A = placebo, B = methylphenidate, C = placebo). Blinded outcomes of depression and cognition were measured initially and twice in each phase. Depression was measured using the Hamilton Rating Scale for Depression (HAM-D) and a mood self-assessment scale. Cognition was measured using the digit span (forward and backward subtest of the Wechsler Adult Intelligence Scale-Revised, Trail-Making Tests A and B, and the Symbol Digit Modalities Test (SDMT). RESULTS: HAM-D scores improved during the methylphenidate phase (initial = 33; A = 23, 25; B = 15, 10; C = 28, 27), as did the subjective mood assessment ratings. Digit span backward scores improved with the drug (initial = 4; A = 4, 3; B = 6, 8; C = 5, 4), as did Trail-Making Test B scores (initial = 125 seconds; A = 133, 103 seconds; B = 86, 82 seconds; C = 88, 96 seconds). Digit span forward, SDMT, and Trail-Making Test A, however, showed no drug-related trend. CONCLUSION: We conclude that methylphenidate was beneficial in the treatment of depression in this patient with AIDS. PMID- 1592839 TI - The prevalence of personality disorders in 210 women with eating disorders. AB - BACKGROUND: The purpose of this study was to assess the prevalence, reliability, and predictive value of comorbid personality disorders in a large sample of 210 women seeking treatment for anorexia nervosa (N = 31), bulimia nervosa (N = 91), or mixed disorder (N = 88). METHOD: All subjects were interviewed using the Structured Interview for DSM-III Personality Disorders as part of a longitudinal outcome study of eating disorders currently underway at Massachusetts General Hospital. RESULTS: Of the 210 subjects, 27% had at least one personality disorder; the most commonly observed was borderline personality disorder in 18 subjects (9%). The highest prevalence of personality disorders was found in the anorexia nervosa/bulimia nervosa group at 39%, followed by 22% in the anorexics and 21% in the bulimic sample. We found statistically significant differences regarding the distribution of personality disorders across eating disorder groups. The dramatic personality disorder cluster was differentially distributed across groups; this finding was accounted for by higher rates of borderline personality disorder in the bulimia nervosa and anorexia nervosa/bulimia nervosa groups than in the anorexia nervosa group. The anxious personality disorder cluster was differentially distributed across groups with higher rates in the anorexia nervosa and anorexia nervosa/bulimia nervosa samples. Those subjects with a comorbid personality disorder had a significantly slower recovery rate than those without a comorbid personality disorder. CONCLUSION: The prevalence of personality disorders is not high in treatment-seeking women with eating disorders compared with previously studied samples. The greatest frequency of comorbid personality disorders is in the anorexia nervosa/bulimia nervosa group; this subset also had longer duration of eating disorder illness and much greater comorbid Axis I psychopathology compared with the rest of the sample. Future studies should address whether personality disorders have predictive value in the long-term course and outcome of eating disorders. PMID- 1592841 TI - Falling backward in two elderly patients taking bupropion. AB - BACKGROUND: Bupropion, a novel antidepressant, has been reported to produce fewer adverse effects than the tricyclic antidepressants. It has relatively weak effects on norepinephrine and serotonin reuptake but possesses significant dopamine agonist and reuptake blocking effects. METHOD: The case histories of two geriatric patients treated with bupropion for major depression are presented. RESULTS: Both patients experienced a previously unreported side effect--falling backward--associated with bupropion use. Orthostatic hypotension and vertigo are not consistent with the patients' histories. Both patients manifested other symptoms consistent with parkinsonian syndrome. CONCLUSION: This side effect, apparently unique to bupropion among antidepressants, may be mediated through dopaminergic effects in the basal ganglia. Clinicians should be alert to these potential problems in the geriatric population. PMID- 1592842 TI - Tricyclic antidepressant-induced seizures and plasma drug concentration. AB - BACKGROUND: This study identifies eight patients who during routine therapy with conventional doses of tricyclic antidepressants (TCAs) experienced elevated plasma concentrations and suffered a grand mal seizure. We correlate the incidence of TCA-induced seizures with TCA plasma level and suggest that the incidence of TCA-induced seizures can be significantly reduced with the judicious use of therapeutic drug monitoring. METHOD: Seven of the eight cases of TCA induced seizures during routine pharmacotherapy represent all the cases known to the authors during their careers. Histories were evaluated for factors that would predispose patients to suffer seizures. The following data were also recorded: (1) duration of treatment with the dose that was associated with the seizure, (2) the time between last dose and the seizure, (3) a plasma TCA level obtained at the time of seizure, and (4) presence or absence of other manifestations of TCA toxicity. In addition, a MEDLINE search was conducted using the key phrases "tricyclic antidepressants" and "seizures" to obtain all English language articles published since 1966 on the occurrence of TCA-induced seizures. RESULTS: The mean +/- SD daily TCA dose was 250 +/- 80 mg/day. The mean +/- SD total plasma TCA concentration was 734 +/- 249 ng/mL (range, 438-1200 ng/mL). The only risk factor that emerged for experiencing seizures was an elevated plasma TCA concentration. Three patients presented with no other manifestations of TCA toxicity prior to seizure. CONCLUSION: The incidence of TCA-induced seizures for our inpatient population in which therapeutic drug monitoring is routinely used is 0.4%. This incidence is less than that reported in earlier inpatient series (1% to 4%). Our finding is consistent with the conclusion that therapeutic drug monitoring reduces the incidence of TCA-induced seizures by allowing for rational dose adjustment. PMID- 1592843 TI - Oral contraceptives and panic disorder. AB - BACKGROUND: There are no published reports of an association between triphasic oral contraceptives and the development of panic disorder. METHOD: The authors describe two cases in which the use of triphasic oral contraceptives in women appear to have precipitated panic disorder. Treatment with the triphasic oral contraceptives was stopped and the patients were followed for 2 years. RESULTS: Both subjects had rapid and total resolution of their panic disorder symptoms following cessation of triphasic oral contraceptive medications. CONCLUSION: Triphasic oral contraceptives in some predisposed women may lead to precipitation of panic disorder. PMID- 1592844 TI - A pilot sequential study of cognitive therapy and pharmacotherapy of atypical depression. AB - BACKGROUND: Parallel comparison studies of cognitive therapy and antidepressant medication have suggested that both treatments are effective. However, we cannot determine from these studies whether cognitive therapy and antidepressant medication are effective for the same populations of depressives. A sequential study in which nonresponders to the first treatment are then treated with the second can address this issue. METHOD: Twenty-seven patients meeting DSM-III criteria for major depression or dysthymic disorder and Columbia criteria for atypical depression received cognitive therapy followed by antidepressant medication for cognitive therapy nonresponders. A response rate with the second treatment equal to that expected with placebo would suggest both treatments target the same depressive population. RESULTS: Of the 25 completers of the study, 14 (56%) were judged responders to cognitive therapy alone. Sixty-nine percent (9/13) of the responders maintained their benefits for 6 months or more. Seven of the 11 cognitive therapy nonresponders (63%) responded to antidepressant medication. These results were compared with those of a concurrent double-blind medication study; both its sample and ours were drawn from the same population at the same time: cognitive therapy and antidepressant medication response rates were higher than expected with placebo (28%). CONCLUSION: The results suggest that (1) cognitive therapy and antidepressant medication are effective treatments for differing populations of depressed patients, as the antidepressant medication response of cognitive therapy nonresponders was greater than expected with placebo, and (2) cognitive therapy has a lasting effect. PMID- 1592845 TI - Suicidal and homicidal ideations emerging during a placebo period. PMID- 1592846 TI - Head injury and mood disturbance. PMID- 1592847 TI - Mania self-induced with cough syrup. PMID- 1592848 TI - Fluoxetine-induced yawning and anorgasmia reversed by cyproheptadine treatment. PMID- 1592849 TI - Severe post-partum eclampsia: response to plasma exchange. AB - In their severest forms, pre-eclampsia and eclampsia may be life-threatening complications of pregnancy. We describe a patient with severe post-partum eclampsia characterized by seizures, deep coma, hypertension, renal insufficiency, coagulopathy, and microangiopathic hemolysis. The patient responded to treatment that included intensive plasma exchange, and she achieved full recovery. Our case supports the use of plasma exchange in patients with severe pre-eclampsia and eclampsia. PMID- 1592850 TI - Method for the safe and rapid pretransfusion warming of stored blood: an in vitro and in vivo evaluation of a radiofrequency (RF) instrument. AB - Inadvertent hypothermia due to massive infusion of stored blood can be prevented by pretransfusion warming. One approach is the heating of individual packs by means of electromagnetic conduction, which is a method safely used over the last 25 years. The prototype instrument, which has now been re-engineered, can effectively raise the temperature of a unit of blood to approximately 33 degrees C in less than 3 minutes. Using this new model, we found, in vitro, a modest increase in free plasma haemoglobin, but this was not accompanied by any change in potassium or lactic dehydrogenase levels and the mean red cell fragility was unaltered. In vivo, the survival of autologous red cells that had been stored for 33 days and then infused as a concentrate, having a mean haematocrit of 0.60, was measured at 24 hours and 21 days. Each donor acted as his own control. In paired studies, pretransfusion radiofrequency heating was shown to have no deleterious effect when compared to measurements using the unwarmed blood pack. It is concluded that this method can be recommended as safe. PMID- 1592851 TI - Life-threatening reaction to staphylococcal protein A immunomodulation. PMID- 1592852 TI - Finite-element modelling of femoral shaft fracture fixation techniques post total hip arthroplasty. AB - The presence of a femoral prosthesis superior to a shaft fracture severely complicates fixation and treatment. This study uses two-dimensional, multithickness, plane stress finite-element models of a femur with prosthesis to investigate the stresses developed with the application of three popular fixation techniques: revision to a long stem prosthesis, lateral plating with a cortical bone allograft strut and cerclage wires, and custom plate application with proximal Parham band fixation with distal cortical screws (Ogden plate). The plate and bone contact as well as the fracture site contact were modelled by using orthotropic elements with custom-fit moduli so that only the normal stress to the interface was significant. A thermal analogy was used to model the cerclage and Parham band preloads so that representative preloads in the proximal fixation of the two types of plate treatments could be modelled. A parametric study was performed with the long-prosthesis model to show variations in stem lengths of one, two and three femoral diameters distal to the fracture site. The Ogden plate model showed a transfer of tensile stress near the proximal-most band, with the highest tensile stress being at the fracture site with evidence of stress shielding of the proximal lateral cortex. The cortical bone strut model showed a transfer of tensile stress to the bone strut but showed less shielding of the proximal cortex. The cerclage wires at the base of the bone strut showed the highest changes in load with the distalmost wire increasing to almost four times its original preload.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592853 TI - An analytical and numerical study of the stability of bone remodelling theories: dependence on microstructural stimulus. AB - The origin of unstable bone remodelling simulations using strain-energy-based remodelling rules was studied mathematically in order to assess whether the unstable behavior was due to the mathematical rules proposed to characterize the processes, or to the numerical approximations used to exercise the mathematical predictions. A condition which is necessary for the stability of a strain-energy based remodelling theory was derived analytically using the calculus of variation. The analytical result was derived using a simple elastic model which consists of a long beam loaded by an axial force and a bending moment. This loading situation mimics the coupling between local density and global density distributions seen in vivo. A condition necessary for a stable remodelling scheme is arrived at, but the conditions necessary to guarantee a stable remodelling scheme are not. In this remodelling scheme, the elastic modulus is proportional to volumetric density raised to an exponent n, and the microstructural stimulus is taken as the strain energy density divided by volumetric density raised to an exponent m. In order for a remodelling scheme to be stable in this loading situation, m must be greater than n. Finite-difference time-stepping is used to verify the predictions of the analytical study. These numerical studies appear to confirm the analytical studies. Physiologic interpretation of the behavior found with n greater than m indicates that this type of unstable behavior is unlikely to be observed in vivo. Since numerical approximations are not made in deriving this stability condition, we conclude that the mathematical rules proposed to characterize bone remodelling based on strain energy density should meet this condition to be relevant to physiologic bone remodelling. PMID- 1592854 TI - The physical and mechanical effects of suspension-induced osteopenia on mouse long bones. AB - The present investigation addresses the extent of tail-suspension effects on the long bones of mice. The effects are explored in both sexes, in both forelimb and hindlimb bones, and in both diaphyseal and metaphyseal/epiphyseal bones. Two weeks of suspension provided unloading of the femora and tibiae and an altered loading of the humeri. Whole-bone effects included lower mass (approximately 10%) and length (approximately 4%) in the bones of suspended mice compared to controls. The geometric and material properties of the femora were considered along the entire length of the diaphysis and in the metaphysis/epiphysis portions as a unit. Geometric effects included lower cross-sectional cortical area (16%), cortical thickness (25%) and moment of inertia (21%) in the femora of suspended mice; these differences were observed in both distal and proximal portions of the femur diaphysis. The relative amount of bone comprising the middle 8 mm of the diaphysis was greater (3%) in the control mice than in the suspended mice. Significant mass differences between the group in the metaphysis/epiphysis were not observed. Material effects included lower %ash (approximately 2%) in the femora and tibiae as well as in the humeri of suspended mice compared to controls. With respect to the measured physical and material properties, suspension produced similar bone responses in male and female mice. The effects of suspension are manifested largely through geometric rather than through material changes. PMID- 1592855 TI - Mathematical modelling of the effect of sole elasticity distribution on pronation. AB - A coronal plane model of a distributed elastic sole has been proposed and analyzed with respect to the effects of different medial-lateral elasticity distribution on pronation under quasi-static conditions. The distributed model consists of an array of linear vertical line springs. Under minimum energy assumption, the behavior of the top surface of the interface under resultant force and moment loading was shown to be equivalent to that of a rigid-body mechanism under the same loading. The model was then combined with a rigid-link model of the lower limb. Expressions that describe the relationship of the interface aggregate parameters with pronation and the center of pressure were obtained. These expressions were confirmed by an experiment in which the elastic distribution in the interface was systematically varied and the pronation angle and the center of pressure measured. The model has the potential of being a useful analytical tool in the design of elastic soles in running shoes. PMID- 1592856 TI - Location-dependent variations in the material properties of the anterior cruciate ligament. AB - Our recent anterior drawer studies in human cadaveric knees [Guan and Butler, Adv. Bioengng 17, 5 (1990); Guan et al., Trans. orthop. Res. Soc. 16, 589 (1991)] have suggested that anterior bundles of the anterior cruciate ligament (ACL) develop higher load-related material properties than posterior bundles. This was confirmed when we reevaluated the axial failure data for these bundle-bone specimens from an earlier study [Butler et al., J. Biomechanics 19, 425-432 (1986)]. The purpose of this study was to determine, in a larger data set, if anteromedial and anterolateral bundles of the anterior cruciate ligament exhibit significantly larger load-related material properties than the posterior ligament bundles. Seven ACL-bone units from seven donors (the three tissues from the original study plus four new ones) were subdivided into three subunits, preserving the bone insertions. The subunits were failed in tension at a constant strain rate (100% s-1) and four material properties were compared within and between donors. The anterior bundles developed significantly larger moduli, maximum stresses, and strain energy densities to maximum stress than the posterior subunits. Moduli for the anterior vs posterior subunits averaged 284 MPa vs 155 MPa, maximum stresses averaged 38 MPa vs 15 MPa, and strain energy densities averaged 2.7 N m cc-1 vs 1.1 N m cc-1, respectively. No significant differences were found, however, among strains to maximum stress or between any of the other properties for the two anterior subunits. These results are important to the design of ligament replacements and suggest new experiments designed to distinguish in vivo force levels in these ACL bands, a possible reason for the material differences. PMID- 1592857 TI - Mobility impairment in the elderly: challenges for biomechanics research. AB - The problems of mobility impairment in the elderly constitute new and major challenges for biomechanics research. This paper outlines what some of the important problems are, discusses the relevance of biomechanics research to these problems, and reviews some of the current state of knowledge about factors related to the biomechanics of mobility impairments in the elderly. The population of old adults is growing rapidly and the incidence of mobility impairments in old adults is high. Mobility impairment biomechanics research is needed to make the assessments of impairments more precise, to design therapeutic programs that are more effective and to learn more about how mobility impairments can be prevented. PMID- 1592858 TI - A model for studies of the deformable rib cage. AB - An earlier model for the study of rib cage mechanics was modified so that rib deformity in scoliosis could be better represented. The rigid ribs of that model were replaced by five-segment deformable ribs. Literature data on cadaver rib mechanical behavior were used to assign stiffnesses to the new individual model ribs so that experimental and model rib deflections agreed. Shear and tension/compression stiffnesses had little effect on individual rib deformation, but bending stiffnesses had a major effect. Level-to-level differences in mechanical behavior could be explained almost exclusively by level to level differences in the rib shape. The model ribs were then assembled into a whole rib cage. Computer simulations of whole rib cage behaviors, both in vivo and in vitro, showed a reasonable agreement with the measured behaviors. The model was used to study rib cage mechanics in two scolioses, one with a 43 degrees and the other with a 70 degrees Cobb angle. Scoliotic rib cage deformities were quantified by parameters measuring the rib cage lateral offset, rib cage axial rotation, rib cage volume and rib distortion. Rib distortion was quantified both in best-fit and simulated computer tomography (CT) scan planes. Model rib distortion was much smaller in best-fit planes than in CT planes. The total rib cage volume changed little in the presence of the scolioses, but it became asymmetrically distributed. PMID- 1592859 TI - Finite extension and torsion of papillary muscles: a theoretical framework. AB - We present a new analytical solution for the finite extension and torsion of a nonlinearly pseudoelastic, homogeneous, transversely isotropic, incompressible, solid circular cylinder. This solution can be used to guide the performance and interpretation of experiments, and to identify a specific functional form of a three-dimensional constitutive relation directly from data. We submit, therefore, that this solution can be used by experimentalists to quantify the multiaxial constitutive relations, including shear, of both passive and tonically activated papillary muscles for the first time. PMID- 1592860 TI - Micromechanics modeling of Haversian cortical bone properties. AB - A finite-element micromechanics model for Haversian cortical bone tissue has been developed and studied. The model is an extension of two-dimensional micromechanics techniques for fiber-reinforced composite materials. Haversian systems, or secondary osteons, are considered to be the fiber component, and interstitial lamellar bone the matrix material. The cement line is included as an 'interphase' component along the fiber/matrix interface. The model assumes a regular repeatable spacing of the longitudinally aligned continuous fibers and is, therefore, restricted to approximating Haversian cortical bone in its present form. Haversian porosity is modeled explicitly by incorporating a hollow fiber to represent the Haversian canal. Solutions have been obtained by applying uniform macroscopic stresses to the boundaries of the repeating unit cell model. Macroscopic mechanical property predictions correspond reasonably well with the experimental data for cortical bone, but are necessarily dependent on the input properties for each constituent, which are not well established. The predicted variation in the elastic modulus with porosity is not as sensitive as that observed experimentally. Stresses within the constituents can also be modeled with this method and are demonstrated to deviate from the macroscopic applied stress levels. PMID- 1592861 TI - Quantitative method for comparison of skeletal muscle architectural properties. AB - A numerical method is presented which calculates the architectural difference index between two muscles. This index is based upon the parameters, identified using statistical discriminant analysis, which best characterize the various muscles. This index can be used to reduce multiple architectural properties into a single value and may be useful in selecting donor muscles which are required to perform a substitute function for another muscle which has been lost or injured. PMID- 1592862 TI - Clinical review 34: Androgen treatment of hypogonadal men. PMID- 1592863 TI - Evidence that androgen negative feedback regulates hypothalamic gonadotropin releasing hormone impulse strength and the burst-like secretion of biologically active luteinizing hormone in men. AB - Testosterone injections or pharmacological amounts of dihydrotestosterone infused in men, and androgen-secreting tumors in women, can suppress plasma LH bioactivity assessed in an in vitro rat Leydig-cell bioassay. However, such observations do not define the physiological nature of endogenous androgen feedback actions on the hypothalamo-pituitary axis. To explore the feedback role of endogenous androgen on the male gonadotropic axis, we used a potent, selective, nonsteroidal competitive antagonist of the androgen receptor, flutamide HCl. Eight young men (ages 21-30) each received flutamide (750 mg orally daily x 3 days) and placebo and underwent blood sampling at 10-min intervals for 28 h, the last 2 h of which included two consecutive iv pulses of GnRH (10 micrograms). Plasma bioactive LH concentrations were measured in the rat Leydig cell bioassay. Deconvolution analysis was used to evaluate the number, amplitude, mass, and duration of bioactive LH secretory bursts and simultaneously estimate the half-life of endogenous LH. Flutamide treatment increased mean plasma bioactive LH concentrations from 27 +/- 2.3 to 54 +/- 9.1 IU/L (P = 0.018). Increased LH concentrations were achieved by a significantly amplified mass of LH secreted per burst, which rose from 14 +/- 1.8 (control) to 24 +/- 2.8 (flutamide) IU/L distribution volume. The amplitude (maximal secretion rate) of bioactive LH release episodes also increased from 1.3 +/- 0.21 (control) to 2.2 +/- 0.29 (flutamide) IU/L/min. These responses were specific, since flutamide did not influence bioactive LH half-life [49 +/- 6.5 (control) vs 52 +/- 4.1 (flutamide) min], LH secretory burst duration, frequency, or interburst interval. The total 24-h production rate of bioactive LH rose significantly from 310 +/- 35 (control) to 570 +/- 82 (flutamide) IU/L.day. In contrast, no features of LH secretory bursts evoked by exogenous GnRH pulses were altered significantly by antiandrogen. In summary, in vivo blockade of endogenous androgen negative feedback actions in normal men selectively amplifies the mass and amplitude of bioactive LH secretory bursts without altering their number or duration, or the half-life of LH, or the amount of LH released in response to exogenous GnRH. Therefore, we infer that in the steroid milieu of normal men endogenous androgen acting via the androgen receptor can negatively regulate hypothalamic GnRH stimulus strength, and hence the rate and mass of biologically active LH secretion in vivo. PMID- 1592865 TI - Low molecular weight follicle-stimulating hormone receptor binding inhibitor in sera from premature ovarian failure patients. AB - Ovarian insensitivity to FSH, as observed in some patients suffering premature ovarian failure (POF), could conceivably involve abnormal regulation of local factors that modulate FSH action. Low molecular weight FSH receptor-binding inhibitor (FRBI) has been identified in ovarian follicular fluid and shown to be an antagonist of FSH action. Thus, we undertook these studies to test the hypothesis that elevated FRBI can account for the high serum levels of FSH as measured by RRA relative to RIA values in some POF patients. In order to accomplish this, 2 POF patients were selected from a group of 27 from whom serum FSH had been measured by RIA and RRA. Using a recently developed and validated RRA, FSH was 430 IU (second IRP-78/549)/L and 182 IU/L for serum from patients 1 and 2, respectively. FSH quantitated by RIA was 96 and 136 IU/L in these same serum samples. Thus, the RRA/RIA values for these patients were 4.48 and 1.34. These ratios are: 1) higher than observed for normal cycling women (0.62); 2) higher than observed for normal, postmenopausal women (0.65); and 3) at least 2 SD higher than the mean RRA/RIA ratio of the 27 patients screened. FRBI was separated from FSH in serum from both these patients. FRBI accounted for most of the elevated FSH measured in serum by RRA. The HPLC chromatographic behavior and binding inhibitory activity of FRBI isolated from a large volume of serum from patient 2 were virtually identical to previously observed characteristics of FRBI isolated from porcine follicular fluid. These observations demonstrate that FRBI can account for elevated FSH measured by RRA relative to that measured by RIA. Furthermore, the inhibitor can be biochemically separated from FSH and quantitated by RRA in order to study its postulated relationship to POF. Expanded studies to identify causal relationships between FRBI and ovarian insensitivity to FSH seem warranted at this time. PMID- 1592864 TI - The expression of human chorionic gonadotropin/human luteinizing hormone receptors in human gestational trophoblastic neoplasms. AB - Normal human placental trophoblasts have recently been shown to contain receptors for hCG/hLH. The present studies investigated the expression of these receptors in hyperplastic and anaplastic trophoblasts in gestational trophoblastic neoplasms. The results demonstrated that both hydatidiform moles and choriocarcinomas contained receptor messenger RNA (mRNA) and receptor protein. A variety of nontrophoblast tumors, on the other hand, contained neither receptor mRNA nor receptor protein. Choriocarcinomas contained more receptor mRNA and receptor protein than hydatidiform moles which in turn contained more than normal human placenta. Midluteal phase human corpus luteum contained more receptor mRNA than normal human placenta and about the same as choriocarcinomas. The hyperplastic and anaplastic trophoblasts in hydatidiform moles and choriocarcinomas contained more receptor immunostaining than the normal trophoblasts in the same tissue or those from normal placentas from about the same gestational age. The receptor immunostaining increased as the degree of trophoblast hyperplasia increased in hydatidiform moles. Anaplastic trophoblasts of choriocarcinomas contained a similar amount of receptor immunostaining as severely hyperplastic trophoblasts of hydatidiform moles. Invading anaplastic trophoblasts of choriocarcinoma contained greater amount of receptor immunostaining than the surrounding endometrial stromal and myometrial smooth muscle cells. In summary, this is the first study to our knowledge demonstrating the expression of hCG/hLH receptor gene in gestational trophoblastic neoplasms. The increased receptor expression in these neoplasms suggests that hCG, via its receptors, could play a fundamental and previously unsuspected autocrine role in the regulation of trophoblast transformation, growth, invasion, and high hCG secretion. PMID- 1592866 TI - Determination of aromatase cytochrome P450 messenger ribonucleic acid in human breast tissue by competitive polymerase chain reaction amplification. AB - Local production of estrogen in breast tissue may influence the growth of breast cancers. Peripheral conversion of C19 steroids to estrogens is catalyzed by the aromatase enzyme complex which is comprised of a specific form of cytochrome P450, aromatase cytochrome P450 (P450AROM) and the flavoprotein, NADPH-cytochrome P450 reductase. To evaluate P450AROM mRNA levels in breast tissue, a specific competitive polymerase chain reaction amplification procedure was devised. In this method, a rat P450AROM complementary RNA is coamplified as an internal standard in order to compare amplification reactions. The amplification products are recognized by hybridization with 32P-labeled oligonucleotides specific for each species. Densitometry is used to quantitate autoradiographs. Initial studies using RNA from whole breast tissue obtained from reduction mammoplasty revealed linearity of the relationship between the densitometer signal from the human amplification product and total RNA concentration. Breast tissue was then separated into a floating adipocyte fraction and a pelleted fraction containing the other cellular elements by collagenase digestion and centrifugation. Comparison of specific content of aromatase amplification product per unit weight of RNA extracted from adipocytes and pelleted cells revealed considerably higher levels in the RNA from the nonadipocyte fraction. Immunocytochemical characterization of this fraction revealed the presence of several cell types including macrophages, ductal epithelial cells, and endothelial cells, but primary cells of stromal origin. PMID- 1592867 TI - Influence of pyridostigmine on growth hormone (GH) response to GH-releasing hormone pre- and postprandially in normal and obese subjects. AB - The effect of pyridostigmine (PYR), an inhibitor of acetylcholinesterase, on the GH response to GH-releasing hormone (GHRH) before and after a meal was studied in 14 normal subjects (8 females and 6 males) and 21 obese subjects (13 females and 8 males). In normal subjects tested in a fasting state, PYR was capable of stimulating GH secretion and increasing the GH response to GHRH. These effects were not apparent after food, suggesting a reduction in cholinergic hypothalamic activity. In obese subjects tested in a fasting state, PYR was ineffective when administered alone. On the contrary, it was able to increase the GH response to GHRH. After food, the augmenting effect of PYR on the GH response to GHRH was not observed, whereas a delayed inhibition of the GH response was found after PYR plus GHRH treatment. Our findings support the hypothesis that cholinergic hypothalamic activity plays a pivotal role in impaired GH regulation and the altered sensitivity of GH secretion to metabolic fuels in obese subjects. PMID- 1592868 TI - Pyruvate dehydrogenase activity is stimulated by growth hormone (GH) in human mononuclear cells: a new tool to measure GH responsiveness in man. AB - Human peripheral mononuclear cells (PMC) were used to examine the effects of hGH and insulin on the activity of the pyruvate dehydrogenase (PDH) complex. Incubation of PMC with 10(-7) mol/L hGH or insulin increased basal PDH activity. Hormonal effects were maximal (50-60% above control values) at 15 min. Later on, activation progressively decreased and was no longer detectable at 30 min. Total PDH activity was unaffected by hormonal treatment. PMC were subfractionated into lymphocytes and monocytes to assess the sensitivity of each cell types to the hormones. hGH significantly increased basal PDH activity in lymphocytes and monocytes (38% and 70% above control values, respectively), whereas insulin increased basal PDH activity only in monocytes (151% above control value). PMC from healthy subjects aged 1-45 yr were incubated for 15 min with 10(-7) mol/L hGH or insulin before PDH measurement. An increase of enzyme activity higher than 20% was observed in 26 patients out of 29 with hGH, and in 15 out of 18 with insulin. In conclusion, hGH is able to stimulate PDH activity of human mononuclear cells. This hormonal effect allows rapid evaluation of the cellular responsiveness of hGH in various pathophysiologic situations. PMID- 1592869 TI - Preservation of bone mass in hypogonadal female monkeys with recombinant human growth hormone administration. AB - This study examined the effect of human recombinant GH supplementation on bone loss in female monkeys made hypogonadal with GnRH agonist (GnRH-Ag). Animals were randomly assigned to three treatment groups: vehicle, GnRH-Ag, and GnRH-Ag and GH. After an initial 5-month pretreatment period during which all animals were maintained on a normal monkey chow diet containing a high level of calcium (1%) animals were maintained on a normal monkey chow diet containing a high level of calcium (1%), animals were shifted to a lower calcium diet (0.1%) for 4 to 5 months before the beginning of treatment and were maintained on this diet throughout the remainder of the study. Monkeys were treated continuously for 10 months with 25 micrograms/day GnRH-Ag or vehicle. GH was administered by im injection three times per week at a dose of 100 micrograms/kg body wt/day. Animals treated with GnRH-Ag were amenorrheic throughout the treatment period, and serum estradiol and progesterone levels were below minimum levels of detection. Vehicle-treated animals continued to cycle throughout the study. Monkeys treated with GnRH-Ag alone showed a significant decline (12%) in bone mineral density (BMD) of the lumbar spine. BMD was reduced below pretreatment levels from 6 months of GnRH-Ag treatment through 3 months post treatment in this group. GH supplementation reduced the decline of BMD in GnRH-Ag-treated monkeys. BMD did not change significantly with time in the GH-supplemented group. BMD values in GH supplemented animals between 5 and 10 months of the treatment period exceeded levels in animals treated with GnRH-Ag alone, but BMD levels during this interval were lower than in the vehicle-treated group. In the vehicle-treated group, there was small, but significant, increase in BMD over the course of the study. Serum osteocalcin concentrations were elevated above pretreatment values after 6 and 9 months of GnRH-Ag treatment alone or with GH supplementation, but did not change in vehicle-treated animals. GH also increased serum insulin-like growth factor 1 levels. In response to the lower calcium diet, serum PTH levels increased approximately 200% in vehicle-treated monkeys and animals treated with GnRH-Ag alone. GH attenuated this increase in serum PTH. The data indicate that the level of calcium in the diet of adult monkeys can be reduced more than 10 fold without affecting lumbar BMD provided ovarian function is normal, but if animals are made hypogonadal with a GnRH-Ag, bone mass declines.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592870 TI - Suppression of plasma intact parathyroid hormone levels during insulin-induced hypoglycemia in humans. AB - The adrenergic control of intact PTH secretion was investigated by measuring its plasma concentration during insulin-induced hypoglycemia in normal human subjects under control conditions (n = 12) and after alpha (n = 5)- or beta (n = 6) adrenoceptor blockade. Blood samples were taken at baseline, at the time of the acute hypoglycemic reaction, and at regular intervals for 60 min thereafter. Plasma concentrations of intact PTH, catecholamines, total calcium, magnesium, albumin, phosphate, and glucose were measured in all subjects, and plasma ionized calcium was also assayed in three subjects during acute hypoglycemia without pharmacological blockade. At the time of the acute hypoglycemic reaction, the plasma concentration of intact PTH in the control subjects fell to 60.8% of baseline values and was accompanied by a small but significant increase in plasma total calcium. Intact PTH concentrations remained suppressed after the plasma calcium concentration had returned to normal. The two groups of subjects who were exposed to adrenoceptor blockade exhibited a reduced fall in plasma intact PTH and showed no significant increase in plasma total calcium. Therefore, insulin induced acute hypoglycemia was associated with a fall in plasma intact PTH. Adrenoceptor blockade reduced, but did not abolish, the response, suggesting that other factors are involved. PMID- 1592871 TI - Plasma and cerebrospinal fluid measures of arginine vasopressin secretion in patients with bulimia nervosa and in healthy subjects. AB - Bulimia nervosa is a psychiatric syndrome associated with intense hunger, deficient satiety mechanisms, an obsessional preoccupation with the adverse consequences of eating, ritualistic binge eating, and subsequent purging to forestall the effects of the binge. The morbidity of this illness reflects both the psychological suffering associated with a life organized around pathological eating behaviors, as well as medical complications such as fluid and electrolyte imbalances that occur largely as a result of purging and laxative abuse. We report here a study of the osmoregulation of plasma arginine vasopressin secretion and of vasopressin levels in the cerebrospinal fluid. This study was undertaken because vasopressin not only functions as the antidiuretic hormone, and thus as a principal modulator of fluid and electrolyte balance, but also because, in animals, centrally directed vasopressin delays the extinction of behaviors acquired during aversive conditioning. Thirteen normal-weight female patients with bulimia nervosa were studied after at least 1 month of nutritional stabilization and supervised abstinence from binge eating and purging. Plasma vasopressin, plasma sodium, and subjective thirst were measured serially before and during a 2-h infusion of 3% hypertonic saline (0.1 ml/kg min). In addition, cerebrospinal fluid was obtained by lumbar puncture upon admission and at 1 week before hypertonic saline infusion in 11 of these patients and in an additional 11 female patients who did not participate in the hypertonic infusion study. Fifteen healthy normal weight individuals (4 female, 11 male) served as controls for the hypertonic saline infusion and a separate group of 11 healthy normal weight female controls underwent puncture. Compared to controls, bulimic subjects showed a significant reduction in the plasma vasopressin response to hypertonic saline; in 12/13, plasma vasopressin correlated closely with plasma sodium, whereas in one patient vasopressin fluctuated erratically, with no relation to plasma sodium. Cerebrospinal fluid vasopressin levels were significantly higher in patients, and correlated positively with basal thirst level, which was enhanced in bulimics. Compared to controls, patients showed significant polyuria. We conclude that patients with bulimia nervosa have abnormal levels of vasopressin in their plasma and cerebrospinal fluid during abstinence from binge eating and purging. The disturbance in osmoregulation may aggravate the maintenance of adequate fluid volume in these patients, while the increase in centrally directed vasopressin may have relevance to their obsessional preoccupation with the aversive consequences of eating and weight gain. PMID- 1592872 TI - Pitfalls in diagnosing impaired growth hormone (GH) secretion: retesting after replacement therapy of 63 patients defined as GH deficient. AB - Possible causes of error in the diagnosis of isolated GH deficiency are the variability of GH response to repeated tests, the existence of transient GH deficiencies, and the low GH levels found in short statured children with delayed puberty. Sixty-three patients with variously expressed GH deficiency were retested (1 sleep test and 2 pharmacological tests) after 1-3.9 yr of GH therapy (dose, 15 U/m2.week). Forty-eight subjects had arginine, L-dopa, and sleep tests (mean serum GH concentration) twice, while 15 had only arginine and L-dopa tests. All patients were retested 1 month after withdrawal from therapy. The criteria used to subdivide the patients were pubertal development and response to pharmacological and sleep tests at first diagnosis and on retesting. The initial diagnosis in 33 subjects (52.4%) was not confirmed, and 13 (20.6%) were no longer deficient on retesting. The percentage of normalization was high for the sleep test (43.9%), lower for the pharmacological test (24.5%), and lower still (12.9%) for pharmacological and sleep tests considered together. While none of the 28 subjects who remained prepubertal at retesting normalized in any of the tests, 13 of the 35 subjects retested during puberty did. When normalization was observed in pubertal subjects, it occurred predominantly in the sleep test. Growth velocity and height age/bone age increment ratio after the first year of therapy were no different for the groups of subjects classified according to GH secretion on retesting. Our study demonstrates that a number of children diagnosed as GH deficient do not have a true deficiency. However, such a diagnostic error seems to have little effect, at least in the first year of therapy, on the effectiveness of GH treatment. PMID- 1592873 TI - Changes in bioactive and immunoactive inhibin levels around human labor. AB - The changes in bioinhibin (B-inhibin) and immunoinhibin (I-inhibin) levels were studied in the serum of healthy term pregnant women by ovine pituitary cell culture and immunoenzymatic assay systems before and 24 h after delivery. In the maternal serum, a sharp decline in both B-inhibin and I-inhibin levels was observed within first 6 h after delivery. B-inhibin and I-inhibin in maternal serum were 3.45 +/- 0.25 and 3.77 +/- 0.43 U/mL, respectively, before labor and decreased by 35.82% and 38.89% 30 min after labor. One hour after delivery, B inhibin and I-inhibin were reduced by 56.74% and 61.48%, respectively. After 6 h, B-inhibin and I-inhibin levels were lowered by 93.86% and 78.90%, respectively. Twenty-four hours later, both inhibins were nearly undetectable. In the retroplacental serum, B-inhibin and I-inhibin were 4.92 +/- 0.34 and 10.13 +/- 1.16 U/mL, respectively, i.e. 42.48% and 168.60% higher than the levels of B inhibin (P less than 0.05) and I-inhibin (P less than 0.001) in maternal serum before delivery. In the umbilical cord serum, the B-inhibin concentration was 0.75 +/- 0.16 U/mL, whereas the I-inhibin concentration was 9.58 +/- 0.75 U/mL, which was much higher than that of B-inhibin (P less than 0.001). No difference was found in B-inhibin or I-inhibin levels in the serum samples collected separately from umbilical arteries and veins (P greater than 0.05). In addition, inhibin levels were measured in amniotic fluid and placental extract. In amniotic fluid, B-inhibin and I-inhibin concentrations were 2.37 +/- 0.35 and 8.01 +/- 0.55 U/mL, respectively. In the comparison, B-inhibin in amniotic fluid was 31.3% lower than that in maternal serum before delivery (P less than 0.05), but I inhibin was 112.5% higher than that in the maternal serum (P less than 0.001). In the placental extract, the B-inhibin concentration was 12.80 +/- 0.35 U/g tissue, while the I-inhibin concentration was 33.86 +/- 2.93 U/g tissue, which was more than twice as high as the B-inhibin level (P less than 0.001). Our data provide further evidence that inhibin may be mainly produced in the placenta during pregnancy. PMID- 1592874 TI - Arginine normalizes the growth hormone (GH) response to GH-releasing hormone in adult patients receiving chronic daily immunosuppressive glucocorticoid therapy. AB - Glucocorticoids are thought to inhibit GH secretion through an enhancement of endogenous somatostatin tone. The aim of our study was to evaluate the effect of arginine, a secretagogue that increases GH secretion acting at the hypothalamic level, probably by decreasing somatostatin tone, on GH-releasing hormone (GHRH) induced GH secretion in three male and five female adult patients with nonendocrine disease who were receiving daily immunosuppressive glucocorticoid therapy. Six normal subjects (four males and two females) served as controls. GHRH-induced GH secretion was evaluated after 30-min iv infusion of saline (100 mL) or arginine (30 g) in 100 mL saline. After saline administration, steroid treated patients showed a blunted GH response to GHRH (GH peak, 8.7 +/- 2.4 micrograms/L) compared to that of normal subjects (GH peak, 23.8 +/- 3.9 micrograms/L). The GH responses to GHRH increased (P less than 0.05) after pretreatment with arginine compared to saline pretreatment in both normal subjects (GH peak, 36.6 +/- 4.0 micrograms/L) and steroid-treated patients (GH peak, 28.4 +/- 5.5 micrograms/L). The GH responses to GHRH plus arginine were not significantly different in steroid-treated and normal subjects. Thus, arginine is able to normalize the GH response to GHRH in patients receiving chronic glucocorticoid treatment. Our data are evidence that the stimulatory action of arginine and the inhibitory action of glucocorticoids on GH secretion are mediated by opposite effects on hypothalamic somatostatin tone. PMID- 1592875 TI - Intravenous thyrotropin (TSH)-releasing hormone releases human TSH that is structurally different from basal TSH. AB - To determine whether basal TSH differed structurally from TRH-released TSH, the TSH obtained from 11 normal subjects before and after the iv administration of TRH was characterized using lectin-affinity chromatography. TSH was applied to the following lectins: lentil, ricin (both before and after TSH treatment with neuraminidase), Concanavalin-A, wheat germ, Glycine max, Helix pomatia, Dolichos biflorus, Arachis hypogaea, and Vicia villosa (isolectin B4). After each column was washed to elute unbound TSH, the bound TSH was eluted using the appropriate specific sugar, and TSH in the column fractions was measured by immunoradiometric assay. Basal TSH was found to have a different oligosaccharide composition than TSH in serum 30 min after TRH administration. The basal TSH had fewer core fucose residues and more exposed galactose residues than the TSH released after TRH treatment. The amounts of oligosaccharide branching and the amounts of N acetylglucosamine were similar, and the degrees of sialylation for both basal TSH and TRH-released TSH were highly variable. No exposed N-acetylgalactosamine residues were detected in either type of TSH; if present, these residues may have been uniformly sulfated. The biochemical differences detected in basal TSH vs. TRH-released TSH may reflect different post-translational processing and storage of these molecules in thyrotrophs. These data provide an example of the release of particular isoforms of human TSH depending on a hypothalamic factor, a general principle that may be important in the physiological control of thyroid function by the pituitary. PMID- 1592876 TI - Progesterone inhibits the estrogen-induced gonadotropin surge in the rhesus monkey independent of endogenous opiates. AB - Administration of an estrogen challenge during the luteal phase, a time when progesterone concentrations are elevated, fails to elicit a gonadotropin-positive feedback response. The purpose of the present study was to determine if endogenous opiates are involved in the mechanism by which progesterone blocks the estrogen-induced gonadotropin surge in monkeys. To this end, rhesus monkeys in the luteal phase were pretreated with either saline or various regimens of nalmefene, a long-acting opiate antagonist, before being given an estrogen challenge. Three groups of animals were given nalmefene (10 mg, iv) every 12 h beginning 24, 48, or 96 h before an estrogen challenge and continued until 48 h after the start of the estrogen challenge. A fourth group received a continuous sc infusion of nalmefene (20 mg/day) via osmotic minipumps beginning 48 h in advance of the estrogen challenge. In a second experiment, monkeys in the follicular phase received progesterone implants at the time of an estrogen challenge and iv injections of nalmefene every 12 h for 48 h. Gonadotropin and steroid levels were monitored in both experiments by collecting blood samples by saphenous venipuncture at intervals of 6-12 h. The majority of luteal phase animals that were pretreated with saline were unresponsive to the estrogen challenge. Only 2 of 16 (12.5%) had an increase in LH concentrations that could be classified as a surge. Animals pretreated with iv nalmefene every 12 h beginning 48 h before the estrogen challenge exhibited a higher incidence of positive feedback responses (8 of 12 or 66.7%). A concomitant FSH surge was observed in 3 of these instances. However, when progesterone concentrations, which declined before the estrogen challenge in the nalmefene-treated group, were supplemented with exogenous progesterone, nalmefene failed to evoke any LH surges. Six of 8 animals that received nalmefene by sc infusion exhibited LH responses. However, the amplitude and duration of these LH responses were diminished, and no FSH responses were observed. Monkeys pretreated with nalmefene for either shorter (24 h) or longer (96 h) periods before the challenge were less responsive (0 responses out of 6 trials and 1 response out of 4 trials, respectively). Nalmefene was equally ineffective in preventing progesterone inhibition of the estradiol-induced LH surge in follicular phase animals (0 of 15 animals had LH surge). These results indicate that nalmefene antagonism of endogenous opiates does not enable estrogen to exert positive feedback effects on LH release when progesterone levels are high, such as during the luteal phase or after progesterone administration.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592878 TI - Interferon-gamma reduces the thyroid peroxidase content of cultured human thyrocytes and inhibits its increase induced by thyrotropin. AB - To clarify the role of interferon-gamma (IFN gamma) in autoimmune thyroid diseases, we investigated the effects of IFN gamma on the content of thyroid peroxidase (TPO) and the expression of HLA-DR antigens in cultured normal human thyrocytes. The effect of TSH on the action of IFN gamma was investigated. Immunofluorescence staining and photometric analysis showed that IFN gamma not only induced the expression of DR antigen, but also reduced the content of TPO in a concentration-dependent manner. The addition of TSH increased the content of TPO and enhanced the IFN gamma-induced expression of DR antigen. IFN gamma also inhibited the increase in TPO content induced by TSH. Thus, complex interactions appear to exist between IFN gamma and TSH or thyroid-stimulating antibodies in the modulation of hormone secretion and autoimmune phenomena in the thyroid. PMID- 1592877 TI - Activin-binding proteins in human serum and follicular fluid. AB - Binding proteins that transport and/or modify the biological action of peptide hormones and growth factors have been identified for an increasing number of endocrinologically important substances. Since these binding proteins can mask epitopes critical for recognition in immunoassays and can neutralize the bioactivity of their targets, elucidation of hormonal physiology can be intricately tied to analysis of binding protein structure and function. Therefore, we investigated whether circulating activin- and inhibin-binding proteins exist in human serum by incubating purified recombinant human 125I activin with serum samples. After gel permeation chromatography, radioactive activin was identified in three peaks, a high molecular wt (mol wt) binding protein peak (230 kDa), a lower mol wt binding protein peak (60 kDa), and free activin (22.5 kDa). Bound activin was displaced from the lower mol wt binding protein with either activin or inhibin, but was not displaced from the high mol wt peak with a 10-fold greater concentration of activin. Since an activin-binding protein, follistatin, has been identified in ovarian and pituitary extracts, these same analytical techniques were applied to analysis of human follicular fluid as well. A large, 60 kDa binding protein peak eluting in a position similar to the lower mol wt peak in serum was observed, consistent with this protein being follistatin. These results demonstrate the presence of at least two activin binding proteins, distinguishable by size, in human serum that may interfere with attempts to assay activin levels in circulation without prior extraction, and may also be involved in regulating the biological actions of activin. PMID- 1592879 TI - Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging. AB - Aging has been associated with glucose intolerance, insulin resistance, hyperinsulinemia, and diminished islet B-cell function. The relative contribution of these factors to the aging-associated changes in glucose tolerance has been difficult to discern, particularly so for B-cell function, since insulin sensitivity itself is a determinant of B-cell function and, therefore, comparisons of insulin levels and responses between old and young subjects are difficult. To reduce this effect, we compared B-cell function in 14 healthy older men (aged 61-82 yr; body mass index, 21-30 kg/m2), who were exercise trained for 6 months to improve insulin sensitivity, to that of 11 healthy young men (aged 24 31 yr; body mass index, 19-31 kg/m2), who were also trained. Insulin-glucose interactions were assessed by measuring indices of insulin sensitivity (SI) and glucose effectiveness at zero insulin (GEZI) using Bergman's minimal model. B Cell function was assessed by determining the acute insulin responses (AIR) to glucose (AIRgluc) and arginine at 3 different glucose levels: fasting, approximately 14 mM, and greater than 28 mM (AIRmax). AIRmax provides a measure of B-cell secretory capacity, while the glucose level at which 50% of AIRmax occurs is termed PG50 and is used to estimate B-cell sensitivity to glucose. The insulin sensitivity and glucose effectiveness at zero insulin of the trained older subjects was similar to that of the trained young [SI: old, 5.1 +/- 0.6; young, 6.5 +/- 0.7 x 10(-5) min-1/pM (mean +/- SEM; P = NS); GEZI: old, 1.3 +/- 0.2; young, 1.7 +/- 0.2 x 10(-2) min (P = NS)]. Under these conditions, the fasting glucose levels (old, 5.4 +/- 0.2; young, 5.1 +/- 0.1 mM) and basal insulin levels (old, 49 +/- 6; young, 63 +/- 11 pM) were also similar in the two groups. AIRgluc values were lower in the exercised elderly (old, 253 +/- 50; young, 543 +/- 101 pM; P = 0.01). This decrease in stimulated insulin release was due solely to a reduction in the AIRmax (old, 1277 +/- 179; young, 2321 +/- 225 pM; P less than 0.005); the PG50 was not different (old, 8.9 +/- 0.4; young, 8.8 +/- 0.2 mM; P = NS). These differences in the older subjects were associated with a reduction in iv glucose tolerance (old, 1.49 +/- 0.15; young, 1.95 +/- 0.13%/min; P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592880 TI - Increased glycated Cu,Zn-superoxide dismutase levels in erythrocytes of patients with insulin-dependent diabetis mellitus. AB - Our previous study indicated that erythrocyte Cu,Zn-superoxide dismutase (Cu,Zn SOD) undergoes glycation and inactivation in vivo (1) and in vitro (2). The aim of the present study was to assess glycated Cu,Zn-SOD in patients with insulin dependent diabetes mellitus. Glycated Cu,Zn-SOD, which binds to a boronic acid affinity column, was measured by the enzyme-linked immunosorbent assay. The percentage of the glycated form in 25 insulin-dependent diabetic children was 40.2 +/- 8.2%; this was significantly higher than that in the normal controls (P less than 0.01). The specific activity of the glycated form in the diabetic children was 163,000 +/- 33,000 IU/mg Cu,Zn-SOD protein, significantly lower than that in controls (P less than 0.01). These data indicate that glycated and less active Cu,Zn-SOD is increased in erythrocytes of patients with insulin-dependent diabetes mellitus. PMID- 1592881 TI - Fatty acid-induced increase in serum dialyzable free thyroxine after physical exercise: implication for nonthyroidal illness. AB - In 14 healthy males, prolonged running exercise resulted in a mean 25% increase in serum free T4 (FT4) concentration (P less than 0.001) which was significantly correlated (P less than 0.01-0.02) with an over 5-fold increase in the concentration of serum FFA and the FFA/albumin molar ratio. Hemoconcentration, as reflected in a mean 19% increase in serum albumin, caused an increase in serum T4 binding globulin and therefore also in serum total T4. As there was no change in the serum T4/T4-binding globulin molar ratio, the rise in serum FT4 was probably not caused, or only partly caused, by an exercise-induced shift of T4 from the extravascular to the intravascular compartment. Neither is it likely that the mean 41% increase in serum TSH observed after exercise, partly owing to hemoconcentration, was the reason for the increase in serum FT4 and T4 as there was no correlation between the increases in the TSH and thyroid hormone levels. Further support for the assumption that the elevation in serum FT4 after exercise was FFA-induced was provided by the observation that addition of 2.5 mmol/L oleic acid to normal serum in vitro resulted in a 33% increase in serum FT4 (P less than 0.001). There is an association between increased concentrations of serum FT4 and unsaturated FFA in patients with various nonthyroidal illnesses according to earlier observations, but it is unlikely, in the light of the present data from healthy subjects, that FFA are directly involved in raising the serum FT4 concentration in nonthyroidal illnesses patients unless the serum FFA concentration exceeds 2 mmol/L or the FFA/albumin molar ratio rises above 2.5. PMID- 1592882 TI - Evidence that the human placental 5-monodeiodinase is a phospholipid-requiring enzyme. AB - Gel filtration (GFI) of the solubilized human placental microsomes (SHPMP) performed in an Ultrogel AcA-34 column in the presence of 1 mM 3-(3 cholamidopropyl)dimethylammonio-1-propane sulfonate (CHAPS) plus 10 mM n-octyl beta-D-glucopyranoside (beta-OG) demonstrated two main protein peaks. The 5 Monodeiodinase (5-MD) activity measured by the conversion of [125I]T3 to [125I]3,3'-diiodothyronine in a 2- to 18-h incubation at 37 C in the presence of 10 mM dithiothreitol was detected only in the first peak, and the specific activity was increased about 9 times over that of the starting SHPM. The fractions containing most of the 5-MD activity were filtered through a second Ultrogel AcA34 column (GFII) in the presence of 2 mM CHAPS plus 20 mM beta-OG. In these conditions, 5-MD activity was detected in low amounts only in the second peak. Cation exchange chromatography on carboxymethylcellulose-Sephadex with a starting buffer of pH 5 containing 2 mM CHAPS plus 20 mM beta-OG, followed by a pH 8 buffer, showed a very small OD peak at the void volume (P) and a second peak with about 95% of the protein (E). However, no 5-MD activity was detectable in either peak, while a nearly complete restoration of the enzyme was achieved when P and E were mixed. 5-MD was also completely restored by combination of P with the first inactive peak of GFII. When P was subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis, no distinct protein bands were observed. After ethanol-ether extraction and digestion with H2SO4 and H2O2, inorganic phosphate was detectable only in P, suggesting the presence of phospholipids. We next studied the effect of phosphatidyl serine (PS), phosphatidyl choline (PC), or phosphatidyl ethanolamine (PE) on 5-MD activity of E (5 micrograms protein/mL). The 5-MD activity was recovered in a dose-response manner with all phospholipids studied, but PS was the most effective agent for reconstitution. At 1 microgram/mL, 5-MD activity, expressed as a percentage of the total P plus E activity, was 101% for PS, 35% for PC, and 20% for PE. The addition of rat liver or kidney microsomes (80 micrograms/mL) to E (5 micrograms/mL) provided recoveries of 79% and 48%, respectively, of the total P plus E activity. The following conclusions were reached. 1) Phospholipids are essential for the 5-MD activity of SHPMP. 2) CHAPS and beta-OG may extract phospholipids from the membranes without denaturation of the 5-MD.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592883 TI - Transthyretin (prealbumin) in the pancreas and sera of newly diagnosed type I (insulin-dependent) diabetic patients. AB - We investigated transthyretin (TTR) in the pancreases and sera of 10 newly diagnosed type I diabetic patients by immunohistochemistry and nephelometry. In the type I diabetic pancreases, glucagon-positive A-cells showed strong immunoreactivity for TTR, the intensity and distribution pattern of which corresponded to those in normal subjects. Morphometric analysis revealed that the amount of strongly TTR-positive A-cells was not significantly different from that in normal subjects. On the contrary, insulin-positive B-cells, which normally show uneven and weak TTR immunoreactivity, decreased in number, and only a few residual B-cells showed faint immunoreactivity. Neither somatostatin cells nor pancreatic polypeptide cells were positive for TTR. The serum TTR concentration showed a significant decrease in type I diabetic patients compared with that in normal subjects (P less than 0.005). These data suggest that the synthesis or storage of TTR in A-cells is not affected, but that in B-cells is impaired in type I diabetes. The decrease in serum TTR might be one of the features of metabolic disorders in type I diabetes. PMID- 1592884 TI - Oral administration of growth hormone (GH)-releasing peptide stimulates GH secretion in normal men. AB - Intravenous infusions of the synthetic hexapeptide GH-releasing peptide (His-DTrp Ala-Trp-DPhe-Lys-NH2; GHRP) specifically stimulate GH release in man. To determine whether orally administered GHRP stimulates GH secretion, 10 normal men received oral doses of placebo, 30, 100, and 300 micrograms/kg GHRP, and an iv injection of 1.0 micrograms/kg GHRP at weekly intervals in a single blind, randomized design. Serum GH concentrations were measured in blood samples obtained at 5-min intervals for 1 h (0700-0800 h) before and 4 h (0800-1200 h) after each dose. Mean (+/- SE) peak GH concentrations were 4.0 +/- 1.5, 5.2 +/- 1.6, 9.2 +/- 3.3, 18 +/- 3.7, and 26 +/- 5.6 micrograms/L for placebo; 30, 100, and 300 micrograms/kg oral GHRP; and 1 micrograms/kg iv GHRP, respectively; mean 4-h (0800-1200 h) integrated GH concentrations were 312 +/- 109, 406 +/- 159, 698 +/- 284, 1264 +/- 303, and 1443 +/- 298 min.micrograms/L, respectively. To analyze changes in the pulsatile pattern and amount of GH secretion after the administration of GHRP, a waveform-independent deconvolution method was used to estimate GH secretion rates. Variable increases in GH secretion after placebo and GHRP treatments were observed. Despite this variability, weighted least squares linear regression revealed that increasing doses of oral GHRP progressively stimulated GH secretion (P less than 0.005); similar relationships were observed for the peak GH concentration and 4-h integrated GH concentrations. The GH responses to oral GHRP (300 micrograms/kg) and iv GHRP (1 microgram/kg) were significantly greater than that to placebo (P less than 0.05) and were comparable in magnitude. Pairwise comparisons revealed that increases in GH concentrations and secretion rates after the 30 and 100 micrograms/kg oral doses of GHRP were not significantly different from those after placebo. The increase in GH secretion after GHRP treatment was accounted for entirely by an increase in the amplitude of GH secretory events, as no significant increase in the number of GH secretory pulses was observed. The onset and duration of action of GHRP were analyzed by a proportional hazards general linear regression model. Intravenous GHRP had a more rapid onset of action than all doses of oral GHRP (P less than 0.02). Increasing doses of oral GHRP resulted in earlier GH responses (P = 0.006). However, the duration of the GH response was similar for iv GHRP and all doses of oral GHRP, averaging 120-150 min.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592885 TI - Recovery of parathyroid hormone secretion during correction of tumor-associated hypercalcemia. AB - Spontaneous recovery of parathyroid secretion during correction of tumor associated hypercalcemia by bisphosphonates provides a unique clinical opportunity to further unravel the complex relationship between Ca and PTH levels. We measured plasma ionised Ca (Ca2+) and serum intact PTH concentrations in 31 hypercalcemic cancer patients every 2 (range, 1-3) days over a period of 3 21 (median, 7) days after pamidronate therapy. The mean (+/- SD) initial Ca2+ concentration was 1.64 +/- 0.20 mmol/L (normal, 1.05-1.26 mmol/L), with a corresponding PTH level of 4.9 +/- 2.6 (median, 4.5; range, less than 2.0-14.7) ng/L. PTH levels were subnormal in 30 of 31 patients. During correction of hypercalcemia, the relationship between Ca2+ and PTH concentrations was best described by a polynomial regression (r = 0.89; P less than 0.001). The curve of the regression entered the normal range of PTH levels (10.5 ng/L) for a Ca2+ concentration of 1.21 mmol/L. Similarly, the mean Ca2+ level that caused a reproducible increase in PTH levels compared to baseline values was 1.21 +/- 0.12 (median, 1.17; range, 1.00-1.45) mmol/L. Comparable values were obtained when day to day variations in PTH levels were considered; the mean Ca2+ threshold level was 1.24 +/- 0.12 (median, 1.25; range, 1.00-1.43) mmol/L. This PTH secretory threshold was not significantly influenced by several factors, including the type of cancer hypercalcemia, the day to day variations in Ca2+ levels, various biochemical parameters of calcium metabolism, or the number of days to obtain a normal Ca2+ concentration. In summary, contrary to previous reports, our data show that the PTH secretory threshold during correction of tumor-associated hypercalcemia lies in the upper part of the normal range of Ca2+ concentrations and is not significantly influenced by the rate of change in Ca2+ levels. PMID- 1592886 TI - Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. AB - We studied the feasibility of employing the measurement of thyroglobulin (Tg) in the washout of the needle used to perform the fine needle aspiration cytology (FNA-Tg) for the differential diagnosis of nonthyroidal neck masses of unknown etiology. We studied 35 patients presenting for 1 or more neck lumps outside the thyroid gland. A previous history of treated differentiated thyroid cancer (DTC) was given by 23 patients and of nonthyroidal malignancy by 3 patients. FNA-Tg was measured in the Tg-free serum used to wash out the needle employed for the cytology. Finally, all patients were treated by surgery. FNA-Tg was always detectable in 14 patients with thyroid cancer metastases demonstrated by histology, with a mean (+/- SD) of 27,087 +/- 37,622 ng/FNA (P less than 0.002) compared to patients without thyroid cancer metastases (mean +/- SD, 12.1 +/- 4.8 ng/FNA in 7 cases; undetectable in 14 cases). Assuming 21.7 ng/FNA (the mean +/- 2 SD of the negative patients) as the cut-off value, all patients with metastases from DTC were detected by FNA-Tg. FNA-Tg had better negative predictive value than cytology, since this last technique gave 10 inconclusive results, comprising 2 false negative results in patients with metastases from DTC. Our results indicate that elevated concentrations of FNA-Tg in nonthyroidal neck nodes strongly suggest the diagnosis of metastases from DTC. PMID- 1592887 TI - Oxyntomodulin-like immunoreactivity: diurnal profile of a new potential enterogastrone. AB - The biological specificity of oxyntomodulin toward the gastric mucosa results from its C-terminal octapeptide. A RIA using a specific antibody raised against this region permitted quantification of the whole set of proglucagon-derived peptides that interact with the oxyntomodulin recognition systems, corresponding to the new concept of oxyntomodulin-like-immunoreactivity (OLI). The present report describes the physiological 24-h OLI profile in human plasma (eight men and eight women; mean age, 45 yr; range, 20-77 yr). Blood was withdrawn every hour from 0700-1900 h and every 2 h from 2100-0500 h. A meal-dependent profile was found for circulating OLI, with basal values (60 +/- 7 ng/L) at 0500 h and rises elicited by each food intake. The highest value (136 +/- 21 ng/L) was obtained at 2100 h. Plasma concentrations and diurnal variations of OLI were similar to those of the other intestinal peptides known to exert an endocrine function. The mean circulating OLI values increased with age, whereas no change was noticed according to sex. The inhibitory effect exerted by the peptides of the OLI family on gastric acid secretion, the meal dependence of their plasma concentrations, and the observed synchronism of their diurnal profile with that previously described for somatostatin make them candidates for an enterogastrone action. PMID- 1592888 TI - Inhibition of the morning cortisol peak abolishes the expected morning decrease in serum osteocalcin in normal males: evidence of a controlling effect of serum cortisol on the circadian rhythm in serum osteocalcin. AB - Osteocalcin (OC) in serum varies in a remarkably constant circadian rhythm with zenith at night and nadir in the morning. The factors controlling this rhythm are unknown, but several studies indicate that serum cortisol could be of major importance. We tested this hypothesis in a double-blind, placebo-controlled, cross-over study comprising 10 normal male volunteers (aged 23-31 yr) by measuring the response in serum OC and cortisol rhythms to a single dose of metyrapone (30 mg/kg body weight) administered at midnight. During placebo, serum cortisol consistently peaked early in the morning before 0730 h. Ingestion of metyrapone at 2400 h significantly postponed and flattened this peak (P less than 0.01). On both occasions, serum OC increased towards peak levels around 0300 h (P less than 0.01) with no overall differences in the OC profiles. However, when the serum OC time series were synchronized according to the individual cortisol nadirs, we found a significant (P less than 0.01) decrease in serum OC on the placebo day approximately 4 h after the cortisol nadir, whereas no significant changes (P greater than 0.50) were seen on the metyrapone day. Moreover, the mean serum OC level tended to be higher (P less than 0.10 in the interval 0-12 h, and P = 0.06 in the interval 4-8 h) on the metyrapone day compared with the placebo day. On the placebo day, the mean level of serum cortisol during the interval 0-4 h correlated inversely with the mean level of serum OC in the interval 4-8 h (r = 0.77, P less than 0.05). This relation was not found on the metyrapone day. In conclusion, administration of metyrapone, which reduced and postponed the early morning cortisol peak, abolished the normal morning decrease in serum OC. This strongly supports that changes in endogenous serum cortisol are of major importance for the circadian rhythm in serum OC. PMID- 1592889 TI - The biochemical phenotypes of two inborn errors in the biosynthesis of aldosterone. AB - Two inborn errors in the methyl oxidation of corticosterone to form aldosterone correspond to the two oxygenation-hydroxylation reactions required for this transformation. Both defects are characterized by overproduction of corticosterone of glomerulosa zone origin and deficient synthesis of aldosterone. In the type 1 corticosterone methyl oxidase defect (CMO I) impairment in the first step is reflected in decreased production of 18-hydroxycorticosterone while in CMO II an impaired second step is characterized by overproduction of 18 hydroxycorticosterone leading to an increased 18 hydroxycorticosterone:aldosterone metabolite ratio as a diagnostic index. This metabolite ratio may be increased somewhat in CMO I but not as much as in CMO II. The absolute value of 18-hydroxycorticosterone is a more reliable discriminator as is the corticosterone:18-hydroxycorticosterone metabolite ratio which is increased in CMO I and decreased in CMO II. On the basis of these findings, a North American kindred is reclassified as CMO I making this defect the more prevalent form in the Western Hemisphere. The two biochemical phenotypes will very likely describe different mutations in the gene encoding cytochrome P-450 CMO. PMID- 1592890 TI - Gastrin (G) cells are the cellular site of the gastric thyrotropin-releasing hormone in human fetuses and newborns. A chromatographic, radioimmunological, and immunocytochemical study. AB - In this study we analyzed the ontogeny and location of gastric TRH in human fetuses, preterm and term newborns, and adults. TRH immunoreactive cells were found in the antrum towards the bottom of developing glands and double immunostaining demonstrated that this neuropeptide is coexpressed with gastrin in the same cell (G-cell). In the youngest fetuses studied (12 weeks) G cells were few and contained both gastrin and TRH. They increased in number during development and were most abundant between 26 and 36 weeks of gestation. These morphological data correlated with total immunoreactive TRH content extracted from the whole stomachs of six fetuses and two preterm infants. On the contrary G cells containing both hormones were decreased in the newborn at term and not identified in the adult whereas those containing only gastrin were numerous in both. The TRH extracted was indistinguishable from synthetic TRH using chromatographic, radioimmunologic, and enzymatic criteria. As has already been reported, TRH was found in insulin-containing cells of the islets of Langerhans in the pancreas of our fetuses and newborns. These cells presented a similar development pattern to the gastric G cells. PMID- 1592891 TI - Lower serum ionized calcium and abnormal calciotropic hormone levels in preeclampsia. AB - Relative hypocalciuria has been reported in women with preeclampsia. However, there has been no systematic explanation for this finding. We measured serum and urinary calcium and serum calciotropic hormones in third trimester women with preeclampsia (n = 12, gestational hypertension and proteinuria) and with normotensive pregnancies (n = 24) to try to explain these changes. We confirmed that the women with preeclampsia have a relative hypocalciuria (2.9 +/- 0.7 vs. 6.5 +/- 0.2 mmol/day, P less than 0.01). Preeclamptic women also had lower serum ionized calcium than normotensive third trimester pregnant women (1.20 +/- 0.01 vs. 1.26 +/- 0.01 mmol/L, P less than 0.02). Intact PTH levels were significantly higher in preeclamptic women (29.9 +/- 4.3 vs. 15.4 +/- 1.3 ng/L, P less than 0.01) and a significant inverse relationship was observed between PTH and both urine calcium (r = -0.60, P less than 0.0001) and serum ionized calcium (r = 0.36, P less than 0.05). We measured vitamin D metabolites in a subgroup of both normotensive and preeclamptics. Preeclamptic and normotensive pregnant women had equivalent levels of 25-hydroxyvitamin D [25(OH)D]; however, preeclamptics had significantly lower 1,25-dihydroxyvitamin D [1,25-(OH)2D] levels (172.1 +/- 18.5 vs. 219.6 +/- 12.7 pmol/L, P less than 0.05). Lower 1,25-(OH)2D may contribute to suboptimal intestinal absorption of calcium during a time of increased calcium demand resulting in lower ionized calcium, increased PTH, and hypocalciuria in preeclampsia. Abnormalities in calcium homeostasis may contribute to the increased vascular sensitivity documented in preeclampsia. PMID- 1592892 TI - A quantitative estimation of growth hormone secretion in normal man: reproducibility and relation to sleep and time of day. AB - Recent reports, based on measurements of plasma GH levels, have challenged the concept that GH secretion is dependent on sleep and not modulated by circadian rythmicity. Because plasma levels reflect not only the secretory process, but also the effects of distribution and degradation, temporal limits of active secretion and, consequently, synchrony with other physiological events cannot be accurately estimated from circulating concentrations. The present study was undertaken to examine the roles of sleep and time of day in modulating pulsatile GH secretion, using a mathematical procedure (deconvolution) allowing secretory rates to be estimated from peripheral levels. Eight young nonobese healthy men participated each in six separate 16-h studies involving either normal or delayed sleep. Plasma GH levels were measured at 15-min intervals, and GH secretory rates were calculated by deconvolution. Each individual study was preceded by one night of habituation, and sleep was polygraphically recorded in all studies. Repeated measurements of plasma insulin-like growth factor-I (IGF-I) were performed in all subjects. Deconvolution revealed the existence of approximately 20% more GH pulses than detected in the plasma profiles. Large peaks of plasma GH concentrations often reflected the occurrence of a succession of secretory pulses. The total amount of GH secreted varied 10-fold across individual studies, but the within-subject variability (32%) was less than half the across-subject variability (65%). IGF-I levels were also more reproducible for a given subject than across subjects (11% vs. 36% variability) and did not correlate with the amount of GH secreted. During normal waking hours, the GH secretory rate was similar in the evening and the morning. This secretory rate was doubled during wakefulness at times of habitual sleep and tripled during sleep, even when sleep was delayed until 0400 h. A pulse starting within 30 min after sleep onset was present in all profiles with normal sleep and in 13 of 16 profiles with delayed sleep. The amount of GH secreted in response to sleep onset was tightly correlated with the level of secretion during wakefulness (r = 0.92). Almost 70% (57 of 83) of the pulses occurring during sleep were associated with slow wave (SW) stages. The amount of GH secreted in SW-associated pulses was correlated with the amount of SW occurring during the pulse, even when sleep-onset pulses were not considered. We conclude that in normal adult men, the amount of GH secretion and the levels of IGF-I are more reproducible within than across individuals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592893 TI - Sleep, awakenings, and insulin-like growth factor-I modulate the growth hormone (GH) secretory response to GH-releasing hormone. AB - To delineate possible factors influencing the magnitude of the GH response to GH releasing hormone (GHRH), eight young healthy men participated in seven 16-h studies involving saline infusions or injections of 0.3 micrograms/kg GHRH at various times of day and stages of sleep. GH responses were quantified by deconvolution, a procedure allowing for secretory rates to be estimated from peripheral levels. While the plasma responses were monophasic, deconvolution revealed that the secretory response to GHRH generally included several distinct bursts in rapid succession. The intersubject variability of GH responses was very wide, but for a given subject, the response was quite reproducible (mean +/- SEM coefficient of variation, 21 +/- 3%). When GHRH was given during the waking period, the magnitude of the response was directly related to the amount of spontaneous GH secretion, negatively correlated with circulating levels of insulin-like growth factor-I (IGF-I) and was not influenced by time of day. When GHRH was given during slow wave sleep, the magnitude of the response was enhanced. When GHRH was given during rapid eye movement sleep, the response was similar to that observed during wake. Awakenings during sleep consistently inhibited the secretory response to GHRH, and resumption of sleep was associated with a reappearance of the secretory process. Thus, in normal men of similar age and body weight, the GH response to GHRH is dependent on the sleep or wake condition, circulating levels of IGF-I, and, possibly, genetic and lifestyle factors. PMID- 1592894 TI - Increased plasma 5 alpha-androstane-3 alpha,17 beta-diol glucuronide concentration in clinically euthyroid women with suppressed plasma thyrotropin levels: further evidence for generalized tissue overexposure to thyroid hormones in these subjects. AB - It has been reported that plasma levels of 5 alpha-androstane-3 alpha,17 beta diol glucuronide (ADG) are increased in thyrotoxic patients. The present study was carried out to determine whether in clinically euthyroid subjects with suppressed TSH levels, ADG plasma levels would also be increased, suggesting a more generalized tissue overexposure to thyroid hormones. The latter has been suggested from increased sex hormone-binding globulin levels (SHBG) in these subjects. ADG and SHBG levels were measured in a group of 20 euthyroid postmenopausal women, 20 postmenopausal women with clinically evident thyrotoxicosis, and 16 euthyroid postmenopausal women with suppressed TSH levels. The mean ADG level in the thyrotoxic group was 4 times the mean level in the control group, whereas in the group with isolated TSH suppression the mean level was about twice the level in the control group. As levels of dehydroepiandrosterone sulfate, the major precursor of plasma ADG, were not significantly increased in these subjects, these data suggest an increased conversion of dehydroepiandrosterone sulfate to ADG. Together with the increased SHBG levels observed in both thyrotoxic and euthyroid subjects with suppressed serum TSH concentrations, these data support the concept that the TSH-suppressed euthyroid subjects have generalized increased thyroid hormone effects on peripheral tissues. PMID- 1592895 TI - Circulating PTH and PTHrP levels before and after treatment of tumor induced hypercalcemia with Pamidronate Disodium (APD). AB - The effect of lowering ionized calcium on circulating parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP) was assessed in twenty patients with hypercalcemia of malignancy following treatment with Pamidronate Disodium. Ionized calcium levels fell rapidly in all treated patients. PTH concentrations were initially suppressed below normal in 18 patients, but rose from 0.48 +/- 0.42 pmol/L to 3.63 +/- 3.13 pmol/L (p less than 0.01) after treatment, reaching higher than normal values in some patients even in the presence of persistent hypercalcemia. PTHrP concentrations did not change significantly after treatment. These findings are consistent with an increased sensitivity of parathyroid tissue to changes in ionized calcium following prolonged exposure to hypercalcemia. Regulation of tumor secretion of PTHrP by calcium was not apparent within the range of calcium concentrations in this study. PMID- 1592896 TI - Human recombinant follicle-stimulating hormone induces growth of preovulatory follicles without concomitant increase in androgen and estrogen biosynthesis in a woman with isolated gonadotropin deficiency. AB - To evaluate the importance of luteinizing hormone (LH) for normal estrogen production and subsequent development of ovarian follicles, a woman with isolated gonadotropin deficiency (LH; 0.37 IU/L, FSH 1.2 IU/L) was monitored during recombinant human follicle-stimulating hormone (hFSHrec) administration with respect to ovarian follicular growth and steroid production. During the first week (75 IU/day hFSHrec im) a significant rise in serum FSH (4.9 IU/L) was observed in the absence of changes in serum estradiol (E2) concentrations (36-76 pmol/L). During the following five days 150 IU/day hFSHrec was administered resulting in a further increase of serum FSH levels (maximum 8.5 IU/L). Development of multiple follicles--maximum diameter 22 mm as observed by transvaginal sonography--emerged together with a minor rise in E2 levels (from 76 to 236 pmol/L) and with a minimal increase in endometrial thickness (below 6 mm). Six days following the last injection of hFSHrec, aspiration of 3 follicles (13, 15 and 18 mm) was performed and low intrafollicular androstenedione (AD) (less than 675 nmol/L) and E2 (less than 9400 pmol/L) concentrations as compared to normal follicles were found. These first data on hFSHrec administration in the human suggest that; a) FSH alone can induce growth of preovulatory follicles, b) follicle growth does occur in the presence of subnormal E2 levels, c) LH is needed for adequate AD biosynthesis as substrate for aromatase activity. This indicates that growth and steroidogenic granulosa cell activity may be differentially regulated. PMID- 1592897 TI - 40th Annual Meeting of the Pacific Coast Fertility Society. April 8-12, 1992, Indian Wells, California. Abstracts. PMID- 1592898 TI - Brain physiology at the Montreal Neurological Institute: some historical highlights. PMID- 1592899 TI - A safe and effective paradigm to functionally map the cortex in childhood. AB - Conventional cortical stimulation based on pulses of fixed duration briefer than the chronaxie rarely elicit responses in infants and young children. We developed a stimulation paradigm that relies on increments in both stimulus intensity and pulse duration. This approach ensures that stimulation parameters converge to the chronaxie by mathematically minimizing the energy required to elicit a response. In six patients, this paradigm successfully elicited clinical responses and/or afterdischarges at thresholds 5-8 mA below the standard paradigm and at up to 64% lower energy levels. Furthermore, three patients under age 5 years who did not respond to maximal fixed duration stimulation demonstrated afterdischarges and clinical responses when longer pulse durations were utilized. These findings indicate that a paradigm based on dual increments is effective for cortical mapping in children. Furthermore, by ensuring responses at lower energy levels, it may be more efficient for mapping the cortex at all ages. PMID- 1592900 TI - Recording of event-related potentials (P300) from human cortex. AB - Auditory event-related potentials were recorded simultaneously from chronically implanted subdural electrodes and from scalp electrodes in three patients who were being evaluated for surgical treatment of epilepsy. These three cases showed clearly defined scalp-P300 and scalp-N300. A cortex-P300 was recorded from the midtemporal area, and a cortex-N300 was recorded from the inferior frontal area with some reflection at the basal temporal region. There were no potentials from an interhemispheric region. We could not observe any component from the cortex studied corresponding to scalp-recorded N200. Therefore, while the activity generated from the mesial temporal lobe may only make minor contributions to scalp-P300, that generated from the midtemporal area might make a major contribution to the scalp-P300. Additionally, generators of N200, P300, and N300 are different from each other. These findings, together with previous reports regarding the generator source of P300, also suggest that P300 is a complex arising from multifactorial generator sources, including the midtemporal and inferior frontal area. PMID- 1592901 TI - Technology and equipment review. Intracranial electrodes. PMID- 1592902 TI - In honor of Irving T. Diamond. PMID- 1592903 TI - Patterns of GABAergic immunoreactivity define subdivisions of the mustached bat's medial geniculate body. AB - The anatomy and the spatial distribution of neurons and axonal endings (puncta) immunoreactive for glutamic acid decarboxylase (GAD) or gamma-aminobutyric acid (GABA) were studied in the medial geniculate body of the mustached bat (Pteronotus parnellii). The principal findings are that: 1) most GABAergic neurons are present in the dorsal and ventral divisions with few, if any, in the medial division; 2) only a small fraction, about 1% or less, of auditory thalamic neurons are immunopositive; 3) the density of immunoreactive puncta is independent on the number of GABAergic neurons in the thalamic divisions, with the ventral division having the largest number/unit area, the medial division about 75% of this value, and the dorsal division only about 50%; and 4) the form of the puncta was unique to each division, those in the ventral division being medium-sized and comparatively simple, those in the medial division predominantly large, coarse, and complex, while dorsal division ending were finer and more delicate. These patterns recapitulate, with some significant exceptions, those found in the rat and cat. The puncta could originate from several sources; while many may arise from intrinsic GABAergic Golgi type II local circuit neurons, these cells may not be the only or even the principal source. Thus, the dorsal division contains comparatively many immunopositive cells though fewer puncta than might be expected if the bulk of these were to arise from auditory thalamic interneurons. This suggests that other, extrinsic sources, such as the thalamic reticular nucleus, may be the source of such endings. A second point is that the form and density of the puncta is regionally specific within the medial geniculate complex. These local patterns might have a significant and regionally specific role in controlling the differential excitability of auditory thalamic neurons. The distribution of presumptive synaptic endings also has implications for the number and arrangement of glomeruli or synaptic nests. Thus, these circuit elements, which are common to the thalamic nuclei in other species, might play an important role in local synaptic circuits between different types of cells. If so, then the structural variations embodied in these patterns could subserve functional arrangements that differ among species. Such patterns might reflect concomitant physiological differences in the organization of local circuits within the microchiropteran medial geniculate body. PMID- 1592904 TI - Frequency tuning properties of neurons in the inferior colliculus of an FM bat. AB - We examined frequency tuning characteristics of single neurons in the inferior colliculus of the echolocating bat, Eptesicus fuscus, in order to determine whether there are different classes of spectral selectivity at this level and to relate frequency tuning properties to the design of the echolocation signal. In unanesthetized but tranquilized animals, we recorded responses from 363 single units to pure tones, frequency-modulated (FM) sweeps, or broad-band noise. Most units were selective for stimulus type; 50% responded only to pure tones, 14% responded only to FM sweeps, and 5% responded only to noise. The remainder responded to two or more types of stimuli. Tuning curves could be classified as follows: 1) V-shaped tuning curves (57%) were the most common type; 2) closed tuning curves (20%) had thresholds at both low and high sound levels; 3) narrow filters (14%) had Q values above 20 at 10 dB and 30 dB above threshold or 10 dB and 40 dB above threshold; 4) frequency-opponent tuning (6%) was found in units with high spontaneous activity; within a center range of frequencies, firing rate increased above spontaneous level, but at higher or lower frequencies, firing rate decreased below spontaneous level; 5) double-tuned units (3%) had two best frequencies (BF). The most clear evidence of topographic distribution was seen for filter units, which were only found in the dorsal part of the 20-30 kHz isofrequency contour. Filter units were also the most clearly related to the echolocation signal of the bat. Their BFs were all within the range of the dominant frequency (approximately 20-30 kHz) that Eptesicus uses during the searching phase of echolocation. PMID- 1592905 TI - Dendritic organization of class II (inter)neurons in the dorsal lateral geniculate nucleus of the tree shrew: observations based on Golgi, immunocytochemical, and biocytin methods. AB - In this report we examine the dendritic organization of putative interneurons (class II cells) in different layers of the dorsal lateral geniculate nucleus of the tree shrew. The results show that there is considerable morphological diversity within this class, but that two broad groups can be identified: neurons whose dendrites remain within a layer or its adjacent interlaminar zones (intralaminar class II cells); and neurons whose dendrites cross into an adjacent layer(s) (interlaminar class II cells). The majority of class II cells in every layer have intralaminar dendrites, some of which are oriented along a particular axis, and others that are organized radially. The paired layers (1 and 2, 4 and 5) contain a particular group of intralaminar class II cells that have radially organized dendrites and elaborate claw-like appendages. The dendrites of interlaminar class II cells are organized along lines of projection and extend across as many as four layers. These cells often reside close to or within the interlaminar zones. Overall, the organization of class II cells seems to follow a pattern similar to the class I (relay) cells identified previously. Most have intralaminar dendrites, which presumably underlie the fidelity of signals transmitted from the retina to a particular layer. However, there are also a number of other cells whose processes cross laminar borders, presumably to affect integrative functions within the nucleus. PMID- 1592906 TI - Somatic sensory responses in the rostral sector of the posterior group (POm) and in the ventral posterior medial nucleus (VPM) of the rat thalamus: dependence on the barrel field cortex. AB - The projection from the whiskers of the rat to the S-I (barrel) cortex is segregated into two separate pathways--a lemniscal pathway relayed by the ventral posterior medial nucleus (VPM) to cortical barrels, and a paralemniscal pathway relayed by the rostral sector of the posterior complex (POm) to the matrix between, above, and below barrels. Before investigating how the barrel cortex integrates these sensory pathways, it is important to learn more about the influence of the various inputs to the two thalamic nuclei. Based on the greater density of descending versus ascending projections to POm, it seemed likely that corticofugal inputs play an important role in the sensory activity of POm. To test this, the responses of POm and VPM cells to sensory stimuli were measured before, during, and after suppression of the S-I cortex. S-I was suppressed by application of magnesium or by cooling; the status of the barrel cortex was assessed continuously by an electrocorticogram. All VPM cells (n = 8) responded vigorously to whisker movement even when the barrel cortex was profoundly depressed. In contrast, all POm cells (n = 9) failed to respond to whisker movement once the barrel cortex became depressed, typically about 25 minutes after the start of cortical cooling or magnesium application. POm cells regained responsiveness about 30 minutes after the cessation of cortical cooling or the washoff of magnesium. These findings indicate that the transmission of sensory information through the lemniscal pathway occurs independently of the state of cortex, whereas transmission through the paralemniscal pathway depends upon the state of the cortex itself. PMID- 1592907 TI - Ultrastructural studies of retinal, visual cortical (area 17), and parabigeminal terminals within the superior colliculus of Galago crassicaudatus. AB - The morphology and synaptic relationships of anterogradely labeled retinal, visual cortical (area 17), and parabigeminal terminals have been analyzed within the superficial gray (stratum griseum superficiale) of Galago crassicaudatus. Our data regarding the retinocollicular projection reveal two populations of terminals based upon size. The population of smaller terminals are found in clusters, while the larger occur in isolation. Both populations of retinocollicular terminals form synapses primarily with dendritic spines, but synapses upon pale vesicle filled (PVF) profiles and dendritic shafts also occur. Corticotectal terminals contain round vesicles and make asymmetrical synapses, primarily onto dendritic spines; few form synapses with PVF profiles. Our findings suggest the possibility that there are two populations of corticotectal terminals based upon differences in size and morphology. Parabigeminotectal profiles contain densely packed round vesicles and make asymmetrical synapses. These terminals, which are exclusively cholinergic in Galago, are presynaptic to dendrites of various sizes. Convergence of retinal and cortical terminals has been observed. This convergence occurs on distinctly separate regions of the postsynaptic membrane. In contrast, convergence of retinal and parabigeminal terminals occurs on the same region of the postsynaptic cell(s). PMID- 1592908 TI - Oxygen transport and cardiovascular responses in skipjack tuna (Katsuwonus pelamis) and yellowfin tuna (Thunnus albacares) exposed to acute hypoxia. AB - Responses to acute hypoxia were measured in skipjack tuna (Katsuwonus pelamis) and yellowfin tuna (Thunnus albacares) (approximately 1-3 kg body weight). Fish were prevented from making swimming movements by a spinal injection of lidocaine and were placed in front of a seawater delivery pipe to provide ram ventilation of the gills. Fish could set their own ventilation volumes by adjusting mouth gape. Heart rate, dorsal and ventral aortic blood pressures, and cardiac output were continuously monitored during normoxia (inhalant water (PO2 greater than 150 mmHg) and three levels of hypoxia (inhalant water PO2 approximately 130, 90, and 50 mmHg). Water and blood samples were taken for oxygen measurements in fluids afferent and efferent to the gills. From these data, various measures of the effectiveness of oxygen transfer, and branchial and systemic vascular resistance were calculated. Despite high ventilation volumes (4-7 l.min-1.kg-1), tunas extract approximately 50% of the oxygen from the inhalant water, in part because high cardiac outputs (115-132 ml.min-1.kg-1) result in ventilation/perfusion conductance ratios (0.75-1.1) close to the theoretically ideal value of 1.0. Therefore, tunas have oxygen transfer factors (ml O2.min-1.mmHg-1.kg-1) that are 10-50 times greater than those of other fishes. The efficiency of oxygen transfer from water in tunas (approximately 65%) matches that measured in teleosts with ventilation volumes an order of magnitude lower. The high oxygen transfer factors of tunas are made possible, in part, by a large gill surface area; however, this appears to carry a considerable osmoregulatory cost as the metabolic rate of gills may account for up 70% of the total metabolism in spinally blocked (i.e., non-swimming) fish. During hypoxia, skipjack and yellowfin tunas show a decrease in heart rate and increase in ventilation volume, as do other teleosts. However, in tunas hypoxic bradycardia is not accompanied by equivalent increases in stroke volume, and cardiac output falls as HR decreases. In both tuna species, oxygen consumption eventually must be maintained by drawing on substantial venous oxygen reserves. This occurs at a higher inhalant water PO2 (between 130 and 90 mmHg) in skipjack tuna than in yellowfin tuna (between 90 and 50 mmHg). The need to draw on venous oxygen reserves would make it difficult to meet the oxygen demand of increasing swimming speed, which is a common response to hypoxia in both species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1592909 TI - The functional significance of ventilation frequency, and its relationship to oxygen demand in the resting brown long-eared bat, Plecotus auritus. AB - Mean oxygen consumption and simultaneous ventilation frequency of nine non reproductive brown long-eared bats (body mass 8.53-13.33 g) were measured on 159 occasions. Ambient (chamber) temperature at which the measurements were made ranged from 10.8 to 41.1 degrees C. Apneic ventilation occurred in 22 of the 59 measurements made when mean oxygen consumption was less than 0.5 ml.min-1. No records of apneic ventilation were obtained when it was over 0.5 ml.min-1. The relationship between ventilation frequency and mean oxygen consumption depended on whether ventilation was apneic or non-apneic. When ventilation was non-apneic the relationship was positive and log-linear. When ventilation was apneic the relationship was log-log. Within the thermoneutral zone ventilation frequency was not significantly different from that predicted from allometric equations for a terrestrial mammal of equivalent body mass, but was significantly greater than that predicted for a bird. A reduction in the amount of oxygen consumed per breath occurred at ambient temperatures above the upper critical temperature (39 degrees C). PMID- 1592910 TI - Seasonal changes in thyroid-gonadal interactions in the edible dormouse, Glis glis. AB - This study was conducted to determine changes in thyroid-gonadal interaction in the edible dormouse during the phase of the annual cycle that corresponds to the end of the breeding season (from June to September). We evaluated intra hypothalamic luteinizing hormone-releasing hormone (LHRH) content, and plasma concentrations of luteinizing hormone (LH), testosterone, thyroid-stimulating hormone (TSH) and thyroxine (T4) in three groups of dormice: (1) controls; (2) dormice receiving sufficient T4 supplementation to maintain June levels in control animals until September, thus counteracting the seasonal reduction of T4 that normally begins in July; and (3) thyroidectomized dormice. The effect of thyroidectomy was only detectable in June, when plasma T4 concentration in the control group was maximal, and consisted of a significant decrease in plasma testosterone levels. This provides strong support for the hypothesis that thyroid function positively influences gondal function during the breeding season. The T4 supplementation resulted in a decrease in hypothalamic LHRH concentration, suggesting that an increased LHRH release led to the observed stimulated hypophyseal secretion of LH in June and September and the increased circulating testosterone levels in September. There was no detectable effect in July and August. These results show that thyroid axis activation of the hypothalamic pituitary-gondal system is only possible during certain phases of the annual cycle, particularly evidenced here during the breeding season. They also reinforce our conclusions drawn from the thyroidectomy results. Conversely, the summer testicular regression which normally occurs after the breeding season is no longer controlled by plasma T4 levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592911 TI - Evidence for the presence of A1 and A2 adenosine receptors in the ventral aorta of the dogfish shark, Squalus acanthias. AB - Isolated, endothelium-free rings of vascular smooth muscle (VSM) from the ventral aorta of the dogfish shark, Squalus acanthias, were used to examine the vasoactive effects of various adenosine agonists. Cumulative addition of 2 chloroadenosine (2 Cl-ADO) over the concentration range 10 nM-1 mM resulted in a biphasic response, with a significant increase in tension at 1 microM and a more significant decline in tension at 100 microM and 1 mM, suggesting that this tissue may possess both A1 and A2 adenosine receptors. N6-Cyclopentyladenosine (N 6 CPA) and N6-(2-phenylisopropyl)adenosine, R(-)isomer (R-PIA), generally considered to be more A1 specific, also produced slight, but significant increases in tension, but only at relatively high concentrations. The more specific A1 agonist, N6-(25)-[2-endo-norbonyl] adenosine [(S)-ENBA] produced a significant increase in tension at 1 pM, reaching 28% above control at 10 nM. The response to (S)-ENBA was also biphasic, with a fall in tension at 10 microM. The relatively non-specific agonist 5'-N-ethylcarboxamidoadenosine (NECA) produced a small, but significant, increase in tension at 1 microM, with no subsequent decline in tension at higher concentrations. These results allow us to assign a tentative structure-activity relationship (SAR) for an increase in tension of (S) ENBA much much greater than R-PIA greater than or equal to 2-Cl ADO = N-6 CPA = NECA; for the decrease, the SAR is (S)-ENBA greater than 2-Cl ADO greater than R PIA greater than N-6 CPA = NECA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592912 TI - Proton NMR spectroscopy of cerebral metabolic alterations in infantile peroxisomal disorders. AB - Noninvasive studies of cerebral metabolism were performed with use of localized proton MR spectroscopy (MRS) in both healthy controls (n = 4, age 6 weeks to 2 years) and infants (n = 4, age 3-15 months) who had impaired peroxisomal functions classified as variants of Zellweger syndrome. All patients revealed a marked decrease of N-acetylaspartate in white and gray matter, thalamus, and cerebellum, indicating impairment of normal neuronal development as well as neuronal loss. In two cases an increase of cerebral glutamine and a decrease of the cytosolic polyol myo-inositol in gray matter and striatum reflected the impact of a concomitant effect on hepatic function. Two cases 3 and 6 months of age exhibited a notable elevation of mobile lipids and/or cholesterol in white matter. These patients with severe disease died within 4 weeks after the MRS examination. While an increase of free fatty acids generally associated with a lysosomal storage disease was not consistently observed by proton MRS of brain, this technique provides a convenient and safe tool for the direct assessment of neuropathologic aspects of Zellweger syndrome such as neuronal degeneration, demyelination, and consequences of compromised liver function. PMID- 1592913 TI - Cervical spine disk herniation: comparison of CT and 3DFT gradient echo MR scans. AB - The purpose of this study was to compare CT and MR for the detection of cervical disk herniations. Nineteen patients suspected of harboring degenerative disk disease of the cervical spine underwent thin contiguous section CT myelography (CTM) and thin contiguous section three-dimensional Fourier transform (3DFT) gradient echo MR at 67 disk levels. Blinded readings of a high intensity CSF MR technique for the presence or absence of disk herniation were performed by three neuroradiologists. The intraobserver CT-MR concordances ranged from 84 to 89%. Using CTM as the paragon test, MR demonstrated a sensitivity of 79-91% and a specificity of 82-88% for disk herniation. Mean MR-CT concordance (86%) was nearly equivalent to that of CT-CT intraobserver concordance (88%). When consensus readings were considered, the MR-CT concordance (91%) was slightly higher than that of CT-CT intraobserver concordance (88%). We conclude that thin section 3DFT gradient echo MR with high intensity CSF is a reliable method to screen for degenerative disk disease in the cervical spine, since the agreement between MR and CTM is comparable with the intraobserver agreement of CTM. PMID- 1592914 TI - Calcium crystal deposition in cervical ligamentum flavum: CT and MR findings. AB - We report three patients with calcium pyrophosphate dihydrate crystal deposition disease within the ligamenta flava of the cervical spine who presented with progressive myelopathy. Plain radiography showed oval calcified nodules at the level of C4-C5 and C5-C6. On computed myelography, oval calcified nodules were seen in the ligamenta flava of the posterior cervical spinal canal compressing the dural sac. Magnetic resonance revealed oval corresponding hypointense foci both on T1-and T2-weighted images. In two cases, the cervical cord showed hyperintensity at the compression site on T2-weighted images. PMID- 1592915 TI - SPIR MRI in spinal diseases. AB - We report on our experience with the fat suppression technique of spectral presaturation with inversion recovery MR in imaging certain spinal disorders. This technique may assist in demonstrating or excluding the presence of fat within a lesion (such as lipoma, dermoid, teratoma) or within a normal structure (i.e., vertebral body or epidural space). The method can also be used to suppress normal fat (such as marrow or epidural fat) thus increasing the conspicuity of adjacent high signal intensity lesions seen on T1-weighted images (such as blood and contrast-enhancing tumors or inflammatory lesions). PMID- 1592916 TI - Meningioangiomatosis: CT and MR findings. AB - Meningioangiomatosis (MA) is a rare hamartomatous lesion of the cerebral cortex; to date only 18 cases with imaging findings have been reported in the English literature. The origin of MA is probably malformative, with possible association with neurofibromatosis. These lesions frequently cause seizures in young patients. We report two new cases seen at our institution and present their CT and MR findings clearly illustrating MA cortex infiltration. Gd-DTPA used in one of the two cases failed to cause enhancement. PMID- 1592917 TI - MR characteristics of meningioma subtypes at 1.5 tesla. AB - Analysis of MR signal characteristics and histopathologic findings confirms the strong correlation between meningioma subtype and observed signal intensity (SI) changes in 24 patients imaged at 1.5 T. On T2-weighted images, 90% of fibroblastic and transitional tumors were hypointense relative to cerebral cortex (SI intermediate greater than SI T2-weighted images); conversely, 66% of meningothelial subtypes displayed persistent hyperintensity (SI intermediate less than or equal to SI T2-weighted images), and the remaining one-third demonstrated mixed high-signal changes. Subtype specific differences in collagen distribution and cellularity, i.e., tumor geometry, appeared to account for these signal trends. Based solely on SI characteristics, correct histologic subgrouping of tumors as either fibroblastic/transitional or meningothelial/angioblastic was possible in 80% (19 of 24) of patients. Utilization of adjunctive imaging features (i.e., mass effect, peritumoral edema, intratumoral cyst formation) in conjunction with signal changes permitted a correct histologic pattern in 96% (23 of 24) of patients. PMID- 1592918 TI - Hyperdense CT foci in treated AIDS toxoplasmosis encephalitis: MR and pathologic correlation. AB - Five AIDS patients with previously diagnosed and treated toxoplasmosis presented with hyperdense precontrast CT approximately 6 months after the CNS infection. An MR study was performed in all cases. The CT hyperdensities were characterized on MR by a high signal intensity on T1 images in four cases. In two of these, pathological correlation confirmed hemorrhage. In the fifth case, MR findings were consistent with calcification, which was verified by pathological examination. PMID- 1592919 TI - CT and MR appearances of parotid pseudotumors in Sjogren syndrome. AB - The radiologic findings in eight patients with parotid pseudotumors associated with Sjogren syndrome (CT in eight; MRI in two) were retrospectively analyzed and compared with the findings in three cases with malignant lymphomas. Diagnosis of pseudotumor was obtained by surgery in six cases and by fine-needle aspiration biopsy and radiologic follow-up in the remaining cases. Six cases (75%) had advanced disease and the remaining had early disease. Both solid (75%) and cystic (38%) masses were seen in the patients with pseudotumors. The masses were solitary in 25%, multiple in 75%, unilateral in 25%, and bilateral in 75%. All three lymphomas were solid masses. The lymphomatous masses were not reliably distinguished from the solid pseudotumors. PMID- 1592920 TI - High resolution CT findings in miliary lung disease. AB - High-resolution CT (HRCT) and chest radiographs were compared in nine patients with miliary lung disease. In all cases, miliary disease was documented to be infectious in etiology; six of these patients proved to be human immunodeficiency virus (HIV) positive. A mixture of both sharply and poorly defined 1-3 mm nodules was seen in all cases, many of the latter having an appearance indistinguishable from airspace nodules. Other features attributable to the presence of nodules included nodular interlobular septae, nodular irregularity of vessels, subpleural dots, and studded fissures. Diffuse intra- and interlobular septal thickening also proved common, seen in all but one case (91%). Based on limited HRCT pathologic correlation, CT findings appear primarily to be due to granulomatous foci developing in a seemingly random distribution involving both pulmonary airspaces as well as the interstitium. It is concluded that in the appropriate clinical setting this constellation of findings is characteristic of miliary disease; the role of HRCT especially in the early diagnosis of miliary disease in HIV positive patients remains to be determined prospectively. PMID- 1592921 TI - CT in tuberculous constrictive pericarditis. AB - Constrictive pericarditis (CP) and restrictive cardiomyopathy have the same pathophysiological disorder (impaired diastolic filling) and a similar presentation. To determine the value of a noninvasive technique, CT, in differentiating between the two, we reviewed the CT scans of 212 patients with clinical signs and symptoms of CP and/or restrictive cardiomyopathy, after 26 cases that did not proceed to surgery were excluded. Computed tomography showed pericardial thickening (greater than 3 mm) in 157 patients with proven tuberculous CP. In two children with proven constriction, the pericardium measured between 2 and 3 mm. We determined that pericardial thickening, in the correct clinical setting, is the only CT sign necessary to diagnose CP. Other CT signs, inferior vena cava dilatation (97%), and deviation of the interventricular septum (15%) were confirmatory. Computed tomography accurately differentiates between CP and restrictive myocardial disease, making more invasive modalities such as cardiac catheterization and endomyocardial biopsy, with few exceptions, unnecessary. PMID- 1592922 TI - Pre- and postoperative CT and MR in pseudoaneurysms of the heart. AB - Pseudoaneurysms of the heart have a propensity to rupture and surgery is indicated. Usually in these cases diagnostic imaging is based on angiographic and/or echocardiographic studies. We have attempted to determine in pre- and postoperative studies the value of CT and ECG-gated MRI in patients with pseudoaneurysm. Seven patients with a pseudoaneurysm and/or dyskinesia of the posterolateral or diaphragmatic wall of the left ventricle were investigated with CT and/or ECG-gated MR studies, in addition to angiography, echocardiography, and radionuclide studies, prior to cardiac surgery. Postoperative follow-up studies with CT in six and MR in five patients were also carried out. Both CT and ECG gated MRI allowed us to visualize the neck and CT also confirmed the communication between the cavities with or without demonstrating the conduit. In addition, disruption of the epicardial fat layer by the pseudoaneurysm was seen on both CT and MR, and the presence of intrapericardial adhesions was visualized on MR. Finally, CT and MRI, in postoperative follow-up studies, may indicate a myocardial discontinuity adjacent to the surgical patch. PMID- 1592923 TI - Pulmonary MR angiography utilizing phased-array surface coils. AB - Magnetic resonance angiography of the pulmonary vasculature was evaluated in 12 subjects using breath-hold gradient echo scans and surface coils at 1.5 T. Flow compensated GRASS, spoiled GRASS (SPGR), and WARP-SPGR sequences were utilized. Comparisons were made among flip angles of 10-60 degrees, slice thicknesses of 3 10 mm, and body coil as well as Helmholtz pair and phased-array multiple coils. With 30-40 contiguous slices encompassing the lung, intrathoracic vasculature was segmented using a UNIX/X-windows based package dubbed VIDA. Three-dimensional anatomy was visualized by a brightest voxel projection algorithm, following reduction of chest wall pixel intensities by an operator-interactive module. Both SPGR (30 degrees flip angle, 4 mm slice thickness) and WARPSPGR (15 degrees flip angle, 5 mm slice thickness) in combination with phased-array multiple coils provided the most satisfactory images, based upon observations by three radiologists and signal-to-noise ratio measurements. The MR angiograms visualized vessels as distal as sixth to seventh order branches. The technique was successfully applied to three patients with pulmonary embolism. The results of this study demonstrate that the pulmonary vascular tree can be imaged by MR angiography combining a high resolution technique utilizing phased-array multiple coils, fast gradient echo sequences with breath-holding, and postprocessing of the volumetric image data. The technique is attractive since it is noninvasive and provides a full three-dimensional portrayal of the pulmonary vasculature. PMID- 1592924 TI - Pneumatosis intestinalis associated with needle catheter jejunostomy tubes: CT findings and implications. AB - The CT findings of pneumatosis intestinalis (PI) associated with needle catheter jejunostomy tubes (NCT) are described in two patients. Each case had cyst-like intramural gas collections associated with the NCT. Neither case had focal bowel wall thickening or portal or mesenteric free air, and there was no evidence of intestinal necrosis. Our findings suggest that cyst-like intramural gas collections associated with NCT represent a benign form of PI. PMID- 1592925 TI - Epithelioid hemangioendothelioma of the liver: MR and CT findings. AB - The MR imaging features in five patients with hepatic epithelioid hemangioendothelioma (EHE) were correlated with CT and pathologic findings. Two hemangioendotheliomas appeared as multiple nodular lesions with a predominantly peripheral location in the liver. In three more extensive cases, the tumors formed confluent peripheral lesions with macroscopic invasion of portal or hepatic veins (n = 3), signs of portal hypertension (n = 3), and nodular hypertrophy of uninvolved liver (n = 2). These findings, suggestive of EHE, were well demonstrated by MR imaging and CT. The internal architecture of the tumors was clearly depicted on T2-weighted MR images. Viable tumor peripheries appeared moderately hyperintense relative to liver. The center of the tumors consisted of one or several concentric zones. Hyperintense central zones were composed of loose, edematous connective tissue. Hypointense zones contained mainly coagulation necrosis, calcifications, and scattered hemorrhages. Except for the presence of calcifications, the internal architecture of EHE was better defined by MR imaging than by CT. PMID- 1592926 TI - CT and MR appearances of splenic hamartoma. AB - The MR and CT appearances of two cases of splenic hamartoma are presented. Computed tomography showed a well demarcated low-density mass without calcification. Dense spreading enhancement was seen in one case on dynamic CT, and prolonged enhancement was noted in both. The masses were demonstrated as areas of isointensity on T1-weighted MR images and of high intensity on T2 weighted images. On gadolinium-enhanced T1-weighted images they were shown as areas of high intensity. Prolonged enhancement on postcontrast CT and MR imaging was a useful finding in differentiation of splenic hamartoma from malignant lesions of the spleen, especially from nodular lesions of malignant lymphoma. PMID- 1592927 TI - Intraabdominal desmoplastic small cell tumor: CT and MR findings. AB - The pertinent radiologic findings in two cases of a recently described tumor, intraabdominal desmoplastic small cell tumor, are presented. This is an aggressive, usually lethal malignant neoplasm of the peritoneum occurring in boys and young men with a marked predilection for intraperitoneal spread. In both cases, CT or MR demonstrated a necrotic intraperitoneal mass with peritoneal metastases. Given the limited differential diagnosis, intraabdominal desmoplastic small cell tumor should be strongly considered as a diagnosis of an intraperitoneal neoplasm in young males. PMID- 1592928 TI - CT and MR of neurofibromatosis of the bladder. AB - Neurofibromatosis of the genitourinary system is rare. We present the CT and MR findings of neurofibromas of the bladder in three patients with von Recklinghausen disease (neurofibromatosis, Type 1). In one case, genitourinary involvement was the primary presentation of the disease. Both CT and MR imaging revealed diffuse and nodular bladder wall involvement, along with pelvic sidewall and adjacent soft tissue abnormalities. The CT attenuation coefficients measured near soft tissue density. On T1-weighted spin echo MR images the tumors revealed signal intensity slightly greater than that of skeletal muscle. Neurofibromas showed markedly increased signal intensity on T2-weighted images relative to the surrounding soft tissues, with marked enhancement in two cases imaged following Gd-DTPA administration. Obstructive hydronephrosis was present in all cases, presumably due to neurofibromas involving the trigonal region. Pelvic sidewall tumors were visualized as rounded, nodular masses extending into the obturator foramina. In the evaluation of patients with von Recklinghausen disease, MR imaging, compared with CT, more clearly defined tumor extent within the bladder, pelvic sidewalls, and surrounding soft tissues. PMID- 1592929 TI - CT depiction of prostatic zonal anatomy. AB - The objective of this study was to investigate the frequency of recognition of prostatic zonal anatomy on CT. Computed tomography in 71 patients without known prostate disease was reviewed. Differential attenuation allowed for distinction of the peripheral zone and central gland of the prostate in 24% patients. The peripheral zone was of lower attenuation than the central gland, attributable to relatively increased water content in the peripheral zone. Patients in whom zonal anatomy was evident were significantly older and had prostate glands significantly larger than those in whom the prostate appeared as a homogeneous structure. All patients in whom prostatic zonal anatomy was visualized had received intravenous contrast material injection. Development of benign prostatic hyperplasia nodules within the central gland may contribute to relative increased attenuation or increased contrast enhancement within this region of the prostate gland. PMID- 1592930 TI - MR and CT in the assessment of Poland syndrome. AB - Seven cases of Poland syndrome were investigated with CT and/or MR to assess the extent of the muscle abnormalities of the shoulder girdle. In all cases the absence of the sternocostal head of the pectoralis major was clearly shown, as were any associated abnormalities of the pectoralis minor, serratus anterior, and latissimus dorsi. The latissimus dorsi muscle has an important role in reconstructive surgery and can be difficult to assess clinically. Cross-sectional imaging with CT or MR will give useful information in patients with Poland syndrome requesting anterior axillary reconstruction and breast mound formation. PMID- 1592931 TI - Subtle bone marrow edema assessed by frequency selective chemical shift MRI. AB - Subtle edema in yellow bone marrow from tumors (14 subjects) and osteomyelitis (9 subjects) were examined by selective nonexcitation (SENEX) water imaging using a short five pulse frequency selective excitation with lipid suppression greater than 96%. Standard spin-echo (SE) proton density-, T1- and T2-weighted images, and fat suppression methods such as short inversion time inversion recovery and also the chemical shift selective Dixon method are discussed in comparison with SENEX. Application of the SENEX method is described and images from four typical cases are demonstrated. Sensitivity to edema is obviously better using the SENEX chemical shift selective method than using other imaging techniques. Improved delineation of abnormal areas in yellow bone marrow is provided by SENEX water imaging in one slice after multislice standard imaging. After shimming, only one SE scan with frequency selective excitation is necessary to get a pure water image. PMID- 1592932 TI - Scatter, spatial resolution, and quantitative recovery in high resolution SPECT. AB - The potential use of single photon emission CT (SPECT) for quantification depends on its physical performance characteristics. We investigated the performance of a high resolution four-head brain SPECT scanner (Neuro-Spect; Summit/Hitachi). With an attenuation coefficient of 0.11 cm-1 and the Chang correction method, the calibration factor of the scanner was 515 (cpm/ml)/(microCi/ml) and showed only a minimal but systematic dependence on object size. Without scatter, the resolution was 4.7 mm (full width at half-maximum); in a scatter medium, the resolution was 5.3-10.0 mm with high resolution collimation and 7.7-18.8 mm with general purpose collimation, depending on filtering. A recovery coefficient of close to 100% was measured in the center of spheres with a size of at least 20 mm placed in a cylindrical water-filled phantom. In lesions of this size, scatter was 20%. We conclude from our measurements that the investigated high resolution SPECT offers significant improvements in resolution, scatter, and recovery, which will improve both the quality of brain studies and the measurement of quantitative parameters such as the cortex/white matter ratio. PMID- 1592933 TI - [11C]methionine quantitation in cancer PET studies. AB - Quantitation of the uptake of positron emitting tracers in cancer patients is still unsettled. A uniform method is needed for comparison of results and for collecting a data base of tumor PET studies. We have measured the tumoral uptake of [11C]methionine in 46 cancer patients using four different methods of analysis. The accumulation of [11C]methionine at 35-40 min after the injection adjusted to the injected dose and body surface area turned out to give similar results as a more complicated method where the uptake rate of [11C]methionine from the plasma to the tumor was calculated (r = 0.92, p less than 0.0001). The results suggest that in clinical [11C]methionine PET studies, 40 min emission scanning with frequent blood sampling is unnecessary. Only a single 5 min emission scan 25-40 min after the injection is required for analysis if the accumulation is adjusted to the injected dose and body surface area. PMID- 1592934 TI - MR angiography of thoracic outlet syndrome. AB - Thoracic outlet syndrome is a disorder caused by neurovascular compression of the brachial nerve plexus and the subclavian artery or vein by bones and muscles. We report the MR angiographic findings of a patient with thoracic outlet syndrome. PMID- 1592935 TI - Pulmonary artery dissection: MR findings. AB - We report a case of pulmonary artery dissection imaged by MR. Dissection of a markedly dilated pulmonary artery is a rare and usually fatal complication of chronic pulmonary arterial hypertension. The diagnosis is made at autopsy, with only two cases having previously been documented (by Doppler echocardiography) during life. The hallmark of an arterial dissection is the finding of an intimal flap and a false lumen. In our case, spin echo MR imaging failed to show either the intimal flap or any intraluminal signal defects. The dissection was presumably obscured by nonhomogeneous intraluminal signal caused by the slow blood flow associated with severe pulmonary arterial hypertension. Cine MR imaging, however, demonstrated different signal intensity within the true and false lumens of the dissection, thereby outlining the intimal flap between the two channels. PMID- 1592936 TI - CT of inflammatory abdominal aortic aneurysm: development from an uncomplicated atherosclerotic aneurysm. AB - The etiology and natural history of inflammatory abdominal aortic aneurysm are poorly understood. We report a case of inflammatory abdominal aortic aneurysm that developed from an uncomplicated aneurysm over a period of 6 1/2 months. PMID- 1592937 TI - Intracranial granulocytic sarcoma: CT, MR, and angiography. AB - Granulocytic sarcoma is a rare, solid tumor composed of immature granulocytes usually found in association with systemic leukemia in younger patients. We present a case of granulocytic sarcoma occurring in an elderly female with no evidence of systemic leukemia. Computed tomography, MR (with and without Gd DTPA), and angiography showed features commonly found in meningiomas. PMID- 1592938 TI - Congenital absence of extraocular muscles: MR demonstration. AB - We describe a case of an infant with complete congenital absence of the extraocular muscles, noted at surgery and confirmed by multiplane MR, which found no evidence of extraocular muscle tissue. This almost certainly represents an extreme form of bilateral congenital fibrosis syndrome. PMID- 1592939 TI - CT findings in cystic schwannoma of the pancreas. PMID- 1592940 TI - Mucinous ductal ectasia of the pancreas: MRI. PMID- 1592941 TI - 3D MR myelography. AB - A three-dimensional (3D) fast imaging with steady state precession sequence structured to maintain constant phase at the radiofrequency pulse, in the presence of motion, was employed to produce high signal intensity of the CSF relative to the extradural and neural structures in 170 consecutive spine MR examinations. In addition to displaying the resulting partitions as two dimensional (2D) images, the acquisition was subjected to a maximum intensity projection postprocessing algorithm for viewing at multiple angles. The projected images demonstrated a global view of the thecal sac and the dural root sleeves. The global depiction of the thecal sac and root sleeves was equivalent to contrast myelography in 15 patients where comparisons were available. These projection myelographic images, used in conjunction with 2D and reformatted 3D cross-sectional images, may provide clinical services with enough information (in a format with which they are comfortable) to eventually eliminate the need for contrast myelography in the evaluation of extradural disease. PMID- 1592942 TI - American Dairy Science Association, 87th annual meeting. June 21-24, 1992, Columbus, Ohio. Abstracts. PMID- 1592943 TI - The processes of therapy. 1940. PMID- 1592944 TI - Introduction to the special section on adult survivors of childhood sexual abuse. AB - Sexual abuse researchers need to use more complex models of abuse and more sophisticated research designs for studying long-term effects and for evaluating treatment programs. The articles that comprise this special section integrate the study of sexual abuse with perspectives on adult victimization, developmental psychopathology, and attachment theory and also offer specific methodological suggestions for improving research on long-term effects and therapy with the abuse survivor. PMID- 1592945 TI - Differential effects of women's child sexual abuse and subsequent sexual revictimization. AB - This study examines the differential effects of sexual revictimization in a community sample of 248 African-American and White American women, ages 18 to 36. Two classifications of sexual revictimization over the life course were used to assess the effects on later sexual and psychological functioning. The findings suggest that unintended pregnancies and abortions were significantly associated with sexual revictimization. Women who reported more than one incident in both childhood and adulthood were also likely to have multiple partnerships and brief sexual relationships. The findings are discussed within the context of the dynamics of sexual revictimization and its effects. Suggestions are offered for therapeutic strategies with survivors in order to minimize the effects of sexual revictimization. PMID- 1592946 TI - Effect of incest on self and social functioning: a developmental psychopathology perspective. AB - The effects of child sexual abuse have become a leading concern of mental health service providers. Despite an explosion of studies, one major difficulty in this research is the lack of a developmentally sensitive model for conceptualizing short- and long-term effects and continuity and discontinuity of effects over time. This article proposes a model based in the perspective of developmental psychopathology. It is argued that incest has its unique negative effects in the domains of self and social functioning, specifically in jeopardizing self definition and integration, self-regulatory processes, and a sense of security and trust in relationships. Studies with clinical samples indicate that diagnostic conditions associated uniquely with a history of incest reflect serious self- and social impairments. A review of the developmental literature on self and social development summarizes each major developmental transition from infancy to middle adulthood, and the implications for the negative effects of incest on development are discussed. Finally, implications for developmentally sensitive research are discussed. PMID- 1592947 TI - Application of attachment theory to the study of sexual abuse. AB - Research on sexual abuse frequently fails to address the influence of the family as a risk factor for the onset of all kinds of sexual abuse and as a mediator of its long-term effects. Attachment theory provides a useful conceptual framework for understanding the familial antecedents and long-term consequences of sexual abuse. Themes associated with insecure parent-child attachment (rejection, role reversal/parentification, and fear/unresolved trauma) are frequently found in the dynamics of families characterized by sexual abuse, and specific categories of sequelae are related to probable attachment experiences. Implications for intervention and research on sexual abuse are suggested. PMID- 1592948 TI - Methodological issues in the study of sexual abuse effects. AB - Despite its relative infancy, child abuse research has provided a substantial literature on the psychological sequelae of sexual molestation. These findings have been helpful in informing social policy and guiding mental health practice. Because of the recency of interest in this area, however, as well as the costs and time investment associated with more rigorous longitudinal research, many of these studies have used correlational designs and retrospective reports of abuse. The implications of this methodology are outlined, and remedies are suggested where possible. PMID- 1592949 TI - Process and outcome research in the treatment of adult victims of childhood sexual abuse: methodological issues. PMID- 1592950 TI - The role of psychological factors in the report of building-related symptoms in sick building syndrome. AB - Sick building syndrome (SBS) is an increasingly common problem, although continued skepticism exists regarding its validity. Because of this, the attribution of complaints to psychogenic causes or mas hysteria persists. In this study (N = 111), self-report measures of psychopathology (Minnesota Multiphasic Personality Inventory [Hathaway & McKinley, 1983] and SCL-90-R [Derogatis, 1983]) and physical symptom reports failed to discriminate symptomatic from nonsymptomatic workers in an affected building but could more generally differentiate workers in the target building from control subjects. These results suggest that SBS cannot be justifiably attributed to psychological factors alone, although working in a contaminated environment appeared to have deleterious psychological consequences for some workers. Smoking history (in pack/years [packs per day x number of years smoked]) was reliably associated with the development of symptoms in exposed workers. Issues related to the assessment of psychological complaints in SBS are discussed. PMID- 1592951 TI - Dysfunctional buildings or dysfunctional people: an examination of the sick building syndrome and allied disorders. AB - As Bauer et al. (1992) have indicated, psychological variables may play a prominent role in workplace-related disorders, like sick building syndrome. To place their work in a broader context, a spectrum of workplace disorders is described that encompasses sick building syndrome, building-related illness, neurotoxic disorders, and mass psychogenic illness. For each disorder, the authors identify both the building- (or exposure-) related variables and the psychological variables believed to trigger or maintain the unique pattern of somatic and neuropsychiatric symptoms. Strategies to aid in diagnostically differentiating the four syndromes are also discussed. PMID- 1592953 TI - Power of the independent samples t test under a prevalent psychometric measure distribution. AB - Studies in psychology often have low power because of inadequate sample size. Thus, recent articles in this journal have suggested making sample size determinations through readily available tables that are based on population normality. Questions have been raised on the use of these power tables because prevalent psychometric distributions, such as the discrete mass at zero with gap that occurs with first use or onset variables, are radically nonnormal. In addition to demonstrating the robustness of the independent samples t test with respect to type I error, the major finding of this study shows that researchers may use these power tables without modification for this radically nonnormal distribution. PMID- 1592952 TI - Evaluating the effects of drugs on behavior and quality of life: an alternative strategy for clinical trials. AB - Conventional clinical trials involve tests of hypotheses with statistics computed from values of dependent variables alone. An alternative is to test hypotheses with statistics computed from benefit/harm scores that measure longitudinal associations between dose and values of the dependent variables. The proposed standardized measure of benefit/harm quantifies the strength of evidence that a patient did either better or worse while on treatment. A benefit/harm score, particularly when obtained from a randomized, N-of-1 trial, indicates a beneficial or harmful treatment effect for the individual. Benefit/harm scores from samples of patients are evaluated with standard statistical tests, with or without group comparisons, to make inferences about populations. The proposed alternative strategy can yield within-patient indicators of treatment effect that are more reliable, valid, comprehensive, and detailed. This, in turn, could help make many population-based clinical trials more informative, cost-effective, and clinically useful for participants. PMID- 1592954 TI - Young adult children of alcoholic fathers: depressive experiences, coping styles, and family systems. AB - College students with alcoholic fathers (adult children of alcoholics, ACA; n = 84) and with nonalcoholic parents (n = 123) were studied with regard to perceptions of their families, depressive experiences, and coping styles within a developmental model of depression that focuses on object representations (Blatt, 1974). Eight measures were used. Multivariate analyses of variance showed that ACAs differed in family perceptions (p less than .0001), with paternal inconsistency discriminating most effectively between groups. As predicted, ACAs exhibited greater introjective depression (p less than .01) but no increase in anaclitic depression. Also, ACAs relied more on aggressive defenses (p less than .01). Findings demonstrate that young adult children of alcoholic fathers manifest distinct, identifiable emotional characteristics and suggest that Blatt's model of depression may provide a useful theoretical context for understanding certain effects of paternal alcoholism. PMID- 1592955 TI - Social support and treatment outcome in behavioral family therapy for child conduct problems. AB - This study assessed the role of social support in the outcome of child management training (CMT) for single parents of conduct problem children and assessed the impact of adjunctive ally support training (AST) on treatment outcome. Single parents (N = 22) with a child diagnosed as oppositional or conduct-disordered received CMT or CMT plus AST. Each group received the same 6-week parent training program and the AST group received an extra social support intervention. Measures of parent behavior, child deviance, social support (SS), and parental depression were obtained at pre- and posttreatment and at 6-month follow-up. Both groups improved, and changes maintained at follow-up. AST produced no extra gains. Responders from either group were more likely than nonresponders to report high levels of SS from friends. Results emphasize the importance of SS and the difficulty of incorporating changes in SS into treatment programs. PMID- 1592956 TI - Shifts in affective balance during cognitive therapy of major depression. AB - Thirty-two outpatient depressives were treated by experienced therapists during a 16- to 20-week, 20- to 24-session cognitive-behavioral therapy (CBT) protocol. Patients were classified as CBT responders (n = 22) or nonresponders (n = 10) on the basis of independent clinical ratings of Hamilton (1960) depression severity. Point and confidence interval estimation procedures yielded results consistent with hypotheses derived from the states-of-mind (SOM; Schwartz & Garamoni, 1986) model. At posttreatment, CBT responders shifted the balance of positivity and negativity to the optimal range, whereas nonresponders remained in a predominantly negative SOM. Response status was related more strongly to change in positivity than in negativity. Findings support the view that clinical response to CBT depends on reducing negativity and increasing positivity until an optimal balance is achieved. PMID- 1592957 TI - Sickle cell disease pain: 2. Predicting health care use and activity level at 9 month follow-up. AB - This study examined 9-month follow-up data obtained from adults with sickle cell disease (SCD) participating in a longitudinal study of pain-coping strategies. Of 99 subjects completing the baseline assessment of pain-coping strategies, 89 (90%) completed a structured pain interview assessing health care use and activity reduction during painful episodes over the follow-up period. Regression analyses controlling for demographics and disease severity revealed that baseline Negative Thinking and Passive Adherence was associated with greater activity reduction and more frequent health care contacts during the subsequent 9 months. Additional correlational analyses revealed that if levels of Negative Thinking and Passive Adherence increased from baseline to follow-up, this increase was associated with even further reductions in activity level during painful episodes. Changes in disease severity were not associated with any of the follow up measures. Comparing pain-coping strategies assessed at baseline to pain-coping strategies measured at follow-up revealed that, without intervention, pain-coping strategies were relatively stable over time. PMID- 1592958 TI - Covert antisocial behavior in boys with attention-deficit hyperactivity disorder: external validation and effects of methylphenidate. AB - Covert antisocial behaviors such as stealing, destroying property, and cheating carry high risk for delinquency. An individual laboratory setting was devised in which youngsters could take desired objects and use answer keys to assist with worksheets. Twenty-two boys with attention-deficit hyperactivity disorder (ADHD) and 22 comparison boys were observed on two occasions, with the ADHD Ss receiving a methylphenidate-placebo crossover. Laboratory stealing and property destruction were positively correlated with maternal and staff ratings of parallel behaviors. Methylphenidate resulted in significant reductions of these acts, but it also effected an increase in cheating, presumably because of its enhancement of task involvement. The generalizability of the laboratory findings, actions of stimulants in this domain, and the ethics of experimental investigations of covert antisocial behavior are discussed. PMID- 1592959 TI - Methylphenidate and attributions in boys with attention-deficit hyperactivity disorder. AB - In Experiment 1, 28 attention-deficit hyperactivity disorder (ADHD) boys underwent a double-blind, placebo-controlled medication assessment in a summer day-treatment program. Daily, boys were asked questions to assess their attributions for and evaluations of their behavior. Objective measures showed improved behavior with methylphenidate; however, boys tended to attribute their performance to effort rather than to medication, particularly when medicated. Experiment 2 involved 38 ADHD boys the following summer and replicated the procedures in Experiment 1, with the addition of a no-pill condition and a comparison of attributions for success and failure outcomes. Simply taking a pill (no-pill vs. placebo comparison) did not show significant effects, whereas the results of Experiment 1 were replicated with placebo-methylphenidate comparisons. Across drug conditions a self-enhancing attributional pattern was obtained; the majority of attributions for success were to ability or effort, whereas attributions for failure were to the pill or to counselors. PMID- 1592960 TI - Perceived social support, social skills, and quality of relationships in bulimic women. AB - The impaired relationship between bulimics and their environment may be important factors in the onset and perpetuation of bulimia. This study explored specific aspects of the bulimic's social network and interpersonal relationships as well as individual difference variables that might mediate her ability to obtain support or perceive this as adequate. Ss were 21 bulimic women and 21 control Ss who completed self-report measures assessing perceived social support, the quality of relationships, social skills, and psychopathology. Bulimics reported less perceived support from friends and family, more negative interactions and conflict, and less social competence. Differences in negative interactions remained significant after controlling for overall psychopathology, and level of conflict was an important predictor of group membership. In addition, bulimics were rated as less socially effective by observers unaware of their group membership. Results highlight the need for further investigation of the quality and type of interactions in bulimic women's lives. PMID- 1592961 TI - Endogenous depression in the elderly: prevalence and agreement among measures. AB - This article describes agreement among diagnoses made according to five definitions of endogenous depression in a sample of 99 depressed elders and discusses the relationship among these systems and selected demographic and clinical characteristics. Poor to fair agreement was generally demonstrated, except for Research Diagnostic Criteria (Spitzer, Endicott, & Robins, 1978) and Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., rev. (American Psychiatric Association, 1987), which demonstrated excellent agreement. Mostly, demographic and clinical variables (e.g., severity of depression) were unrelated to endogeneity diagnoses. The conclusion was reached that these criteria are not all measuring the same construct in older adults and that the relationship between depression severity and endogeneity should be discussed in terms of specific definitions rather than general terms. PMID- 1592962 TI - Predicting patient change from therapist competence and patient-therapist complementarity in short-term anxiety-provoking psychotherapy: a pilot study. AB - In this pilot study, therapist competence and patient-therapist complementarity measured by the Structural Analysis of Social Behavior system (SASB; Benjamin, 1974) were examined as to their interrelation and their unique, collective, and interactive contributions to patient change in 20 sessions of short-term anxiety provoking psychotherapy (STAPP; Sifneos, 1979). Patients were 15 highly educated outpatients, mean age 30 years, with mainly anxiety diagnoses. Therapists were in postgraduate manual-guided STAPP training. Results show that competence in an early session did not relate to patient change. In contrast, patient-therapist complementarity ratings predicted patient change both alone and over and above competence. Predictions were strongest for changes in general distress and dysfunctional attitudes and for shorter term change rather than for longer term change. PMID- 1592963 TI - An in situ model for simultaneous assessment of inhibition of demineralization and enhancement of remineralization. AB - In situ models to assess the ability of oral care products or food components to enhance remineralization and/or inhibit demineralization of tooth enamel or roots must be very carefully designed to minimize the confounding effects of the many variables involved. Controlling these variables as closely as possible is essential if meaningful answers are to be obtained from the models. We have developed an in situ model which combines the experience of several groups. Detailed screening of subjects is essential. Selection criteria should include good general health, good dental health, mandibular partial denture, at least eight natural teeth, no active caries lesions, known fluoride history, normal salivary function, and no medications that affect salivary function. Each subject carries a sound enamel slab and an enamel slab with a pre-formed caries-like lesion (demineralized in vitro) in his/her denture on each side of the mouth for test periods of two or four weeks. The demineralization challenge is controlled by extra-oral immersion of the appliances in sucrose daily. Daily product exposure or daily food component exposure is used as desired. Compliance indicators and a diet diary are included. Whole saliva flow rate (unstimulated), plaque acidogenicity, and salivary fluoride are monitored during the test periods. At the end of the test period, the test slabs are assessed for mineral change, after being sectioned, by means of cross-sectional microhardness or microradiography. The mineral loss or gain (delta M, microns x vol%), compared with adjacent control sections retained in the lab, is calculated as change in delta Z (microns x vol%), namely, delta M = delta ZTEST - delta ZCONTROL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592964 TI - The effect of lesion characteristic on remineralization and model sensitivity. AB - A major criterion for assessing the value of any experimental model in scientific research is the degree of correspondence between its results and data from the real-life process it is designed to model. Intra-oral models aimed at predicting the anti-caries efficacy of toothpastes or other topical treatments should therefore be calibrated against treatments proven to be effective in a caries clinical trial. For this to be achieved, it is necessary that a model with high sensitivity be designed, while at the same time retaining relevance to the process to be modeled. This means that the effects of the various experimental conditions and parameters of the model on its performance must be understood. The purpose of this paper was to assess the influence of two specific factors on the performance of an in situ enamel remineralization model, which is based on human enamel slabs attached to partial dentures. The two factors are initial lesion severity and origin of enamel sample. The results indicated that initial lesion size affected whether net remineralization or net demineralization occurred during in situ treatment. Samples with an initial range of from 1500 to 2500 (delta Z) tended more toward demineralization than did samples with delta Z greater than 3500. This means that treatment groups must be well-balanced with respect to initial lesion size. Differences in initial demineralization severity between different tooth locations must also be considered so that systematic treatment bias can be avoided. The solution used in the model discussed here is based on a balanced experimental design, which allows this effect to be taken into account in the data analysis. PMID- 1592965 TI - The effect of study design on in situ treatment of carious enamel lesions. AB - The aim of this exploratory study was to investigate the influence of several factors on changes in the mineral content of carious enamel lesions treated in situ. The study involved 36 adult volunteers who used either a non-fluoride toothpaste or one of two fluoride toothpastes (1000 or 1500 ppm F). Human enamel specimens were prepared and attached to partial dentures as described previously (Schafer, 1989) and treated in situ for between three and six weeks. The mineral content of lesions was determined by microradiography and computerized densitometry. The factors investigated in this study included study length, frequency of treatment, trial design, patient compliance, patient diet, and previous caries experience of the patient. The effects observed were small, relative to that of the treatment, and not statistically significant (p greater than 0.05). However, the trends in the data were all as would be intuitively predicted. Study duration correlated positively with observed lesion mineral content. Lesions worn by panelists using a fluoride toothpaste for six weeks contained greater levels of mineral with respect to placebo than did those in panelists on a three-week study. The residual variations in the three phases of the study were found to be similar, suggesting that there is no advantage in these studies having a cross-over design. Brushing frequency also correlated positively with observed lesion mineral content, with panelists brushing three times per day with a fluoridated dentifrice having lesions with greater levels of mineral, with respect to placebo, than those brushing twice per day. Overall, no clear relationship between reported diet and changes in lesion mineral levels was apparent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592966 TI - Sample size considerations in designing studies with intra-oral models. AB - Especially during recent years, the use of pre-clinical models for predicting the efficacy of fluoride systems has assumed greater importance within the scientific community. Originally utilized primarily to screen experimental fluoride delivery systems, preclinical models are now being considered as predictors of clinical efficacy in lieu of controlled clinical caries trials. Of the various preclinical models presently available, human intra-oral models have the greatest potential for reflecting intended usage conditions and therefore may be the most meaningful models for predicting clinical efficacy. However, only with the proper consideration of numerous critical variables can studies using intra-oral models be appropriately designed to achieve the desired objectives. Clearly, these models must provide relevant information in a manner which reflects clinically established cariostatic activity and be capable of detecting established differences in the amount of cariostatic activity, i.e., dose-response effects. Three sources of variation must be considered before an appropriate study design and sample size can be chosen. Based on fluoride uptake data from an intra-oral model with proximally-located enamel specimens, estimates of variation among subjects, within subjects, and among specimens within subjects were obtained. Multiple specimens per panelist do not affect the first two sources of variation. Thus, the number of panelists, and not the number of specimens, is of primary importance when pre-test data are used to choose the appropriate study design and calculate the required sample size. PMID- 1592967 TI - The ICT in situ experimental model in dental research. AB - The intra-oral cariogenicity test (ICT) in situ experimental model was introduced in 1964 for the study of caries on sample enamel in the human mouth. Slabs of human or bovine enamel are mounted with a Dacron gauze cover in the acrylic flanges of prosthetic appliances. The extent of enamel demineralization or remineralization of lesions is assessed from surface microhardness measurements and microradiography of the enamel sections. The ICT model offers the potential of studying various parameters related to caries. This publication presents a typical ICT study comparing the cariogenicity of 10% sucrose solutions containing 1, 3, 10, and 30 ppm F with that of the control solution, 10% sucrose (without fluoride). The treatments were applied to the ICT as 10-minute extra-oral immersions. The results indicate: (1) a strong effect of F in decreasing demineralization of sound enamel and increasing remineralization of pre-softened enamel in the ICT; (2) pronounced resistance to a subsequent in vitro acid test; (3) pronounced F incorporation into pre-softened enamel; and (4) a characteristic acid-resistant zone, as seen in microradiographs, associated with exposure to F. This in situ model enables one to study experimental caries with repeated testing of enamel that follows the development and/or the regression of subsurface enamel lesions, F incorporation, increased acid resistance, cariogenicity of substrates, and other parameters of caries that can be assessed under standard conditions of tooth substrate and microbial sheltering. PMID- 1592968 TI - Comparison of fluoride profiles by SIMS with mineral density of subsurface enamel lesions treated intra-orally with a fluoride-releasing device. AB - A variety of intra-oral model systems has evolved which allows for the study of remineralization of coronal and/or root-surface lesions following application of topical fluoride (F) agents. The problem of interpretation of the results has led to a variety of analytical methods (i.e., microhardness, F biopsy, microradiography, and polarizing light microscopy), each of which provides important but limited information related to the overall understanding of remineralization. Microhardness measures change in mineral content which is more precisely localized by microradiography and polarized light microscopy. F biopsy allows for assessment of the F uptake of lesions, but does not suggest the chemical state of the F. Previous work has demonstrated that patterns of mineral deposition during remineralization do not necessarily parallel the F uptake profiles, and fluoridated apatites cannot be distinguished from non-specifically adsorbed F (Clark et al., 1988). Because artificial lesions demonstrate variations in depth and mineral content, complementary analytical methods that demonstrate profiles of both F content and mineral density curves on the same section are needed so that the process of remineralization can be more clearly understood. This study used secondary ion mass spectrometry (SIMS) for F profiles and quantitative microradiography for assessment of mineral deposition on the same section. These state-of-the-art methods demonstrate the precision with which information about remineralization can be obtained. Subsurface lesions in human enamel specimens were developed by immersion in 0.1 M lactate buffer with 1% CMC at a pH of 4.5 for 48 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592969 TI - The in vivo orthodontic banding model for vital teeth and the in situ orthodontic banding model for hard-tissue slabs. AB - This paper presents the orthodontic banding model for vital teeth and the orthodontic in situ model for slabs of enamel, root surface, dentin, or other mineralized tissues such as shark enamel. The model for vital teeth is an in vivo model, since a crevice for plaque accumulation is created behind orthodontic bands on the buccal enamel surfaces of teeth in situ. Visible white-spot lesions are usually seen after a four-week banding period in the absence of fluoride. The microbiological flora developed behind the bands shows a similarity to that of natural caries. Microradiographic data show that the initial lesion is a softening of the enamel surface. Later, a subsurface lesion develops. A modification of the model has been developed for the use of slabs of mineralized tissues. In this model, slabs are mounted on a removable appliance. The slabs are covered with orthodontic banding material for plaque accumulation. Lesion development in enamel in the two model systems is almost identical. The benefit of the in vivo model is that caries development can be studied on vital teeth in young individuals. The model is independent of the patient's cooperation. No special diet is required, e.g., no sucrose rinsing. In the in situ model, slabs could be examined after one study period and then replaced for another period. PMID- 1592970 TI - Oral fluoride measurements for estimation of the anti-caries efficacy of fluoride treatments. AB - The aims of this work were (a) to assess the oral bioavailability of fluoride delivered from dentifrices and (b) to test for a possible link between the results and clinical data obtained with the same dentifrices. Oral fluoride concentrations were measured in samples of saliva and plaque taken from seven subjects, after use of dentifrices which contained 0, 1000, 1500, and 2500 micrograms F/g as sodium monofluorophosphate. Salivary fluoride in samples obtained within the first few hours after a single dentifrice application, or up to 20 h after four weeks' daily use, increased with increasing F content of the dentifrice. For example, the mean zero-time intercepts of the second phase of salivary fluoride clearance curves for the above dentifrices were 0.46, 1.48, 1.88, and 3.03 mumol F/L, respectively. Plaque fluoride measured after four weeks' daily use of the dentifrices exhibited similar dose-response behavior. Linear regression analysis showed these trends to be statistically significant for both saliva (p less than 0.001) and plaque (p less than 0.025). Mean saliva and plaque fluoride concentrations were inversely associated with mean three-year caries increments for the three fluoride-containing dentifrices obtained in a recent clinical trial: DMFS scores 6.80, 6.33, and 5.71, respectively (Stephen et al., 1988). This suggests that oral fluoride measurements are a valuable in vivo method for the evaluation of the potential anti-caries efficacy of fluoride containing dental products. PMID- 1592972 TI - Computer-based image analysis of natural approximal caries on radiographic films. AB - This paper reports on the development of computer software for automatic detection and measurement of approximal caries lesions on digital images obtained from radiographic films. If the program detects a lesion, it defines the lesion's border and measures and reports these lesion parameters: percent mineralization, area, maximum enamel penetration, and mean enamel penetration. Two experiments are reported; both were conducted with the use of extracted human premolar teeth. In the first experiment, thin sections were obtained from 13 approximal surfaces with caries lesions. Microradiographs were made of the sections, and software measurements of the lesions were obtained from the microradiographs. The software was able to separate the lesions into two groups: those that had penetrated less than 100% of the enamel and those that had penetrated 100% of the enamel. The software measurements agreed with evaluation of lesion penetration by polarized light microscopy of the thin sections. In the second experiment, simulated clinical radiographs were made of 16 approximal surfaces, 12 with lesions and four without. Thin sections were obtained for microradiography. Software was used for automatic detection and measurement of the lesions on both types of film. The ability of the software to detect the lesions on the clinical films was compared with that of 10 experienced clinicians. Correlations of the same parameter from the two types of radiographic films were statistically significant, 0.86 less than or equal to r less than or equal to 0.95 and p less than 0.05. The coefficients of variation were low for both microradiographs, 0.4-2.3%, and for clinical films, 0.7-8.5%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1592971 TI - Fluoride availability in human saliva after dentifrice use: correlation with anticaries effects in rats. AB - Studies were conducted to determine fluoride availability in saliva after dentifrice use and to relate this parameter to cariostatic efficacy in rat caries experiments. Three dentifrices--two commercial formulations (Colgate Winterfresh Gel and Crest Dentifrice with Na-Sr-polyacrylate) and an Experimental dentifrice- were compared with respect to salivary fluoride availability. All of the dentifrices tested contained 1100 ppm F as sodium fluoride. It was observed that the Experimental dentifrice and Crest dentifrice with Sr-polyacrylate exhibited low salivary fluoride availability relative to the Colgate Winterfresh Gel. Salivary fluoride availability was assessed by means of two parameters: (a) the fluoride concentration in the dentifrice saliva slurry expectorated after brushing, and (b) the area under the curve of salivary F concentration vs. time for up to two hours after dentifrice use. In two rat caries experiments, it was observed that both the Experimental dentifrice and the Sr-polyacrylate dentifrice provided less cariostatic efficacy than the clinically validated Positive Control (Colgate Winterfesh Gel). Analysis of these data provides further evidence in support of the concept that fluoride availability in saliva following dentifrice use is an important parameter related to anticaries efficacy. PMID- 1592973 TI - Findings from an in situ thin-section sandwich model for evaluating cariogenic and anti-cariogenic activity. AB - This report summarizes the findings from eight individual remineralization studies that used the thin-section sandwich model. This model uses thin sections of human enamel (or dentin) containing caries-like lesions sandwiched between sheets of thin plastic which are then implanted into the buccal surfaces of molars in removable partial mandibular dentures. Toothbrushing with a sodium fluoride-positive control dentifrice for two-week periods always produced positive remineralization of the lesions, and similar use of a placebo always produced mean mineral loss. In most studies, the difference was significant at p less than 0.01. However, variation among specimens placed within an individual mouth were often large and even included cases where one lesion gained mineral while a closely adjacent lesion lost mineral. Similarly, mean mineral changes produced by an individual subject were not consistent from study to study and ranged from net demineralization in one study to net remineralization in another study. Nevertheless, mean mineral changes from all eight studies showed that all subjects produced more remineralization than demineralization when using a sodium fluoride-positive control dentifrice. Data are presented showing remineralization of thin-section lesions from a number of other fluoride and non-fluoride dentifrices and mouthrinses and showing that a product with reduced anti-caries activity (as measured by several tests) also resulted in reduced remineralization by the thin-section model. PMID- 1592974 TI - An in situ enamel section model for assessment of enamel re/demineralization potential. AB - An enamel-section-carrying intra-oral appliance to predict the results of double blind anti-caries studies has been developed. Initial validation was against the F concentration effect attained in a clinical trial where three sodium monofluorophosphate (SMFP) dentifrices were used. Original appliance-based work showed significant differences in remineralization between non-F and F dentifrices, but not between different F dentifrices. However, it was shown later that acidified gel-prepared lesions were not as responsive as solution-prepared lesions to de- and remineralizing processes, and lesion remineralization rates were found to be dependent on initial lesion size. An in situ cross-over study was then repeated with use of acid-solution-created lesions, and seven volunteers completed the project. Each brushed twice daily x 2 min with either 0, 1000, or 2500 ppm F, as SMFP dentifrice. After a two-week wash-out, subjects wore the appliances for four weeks. Enamel mineral content was assessed at 0, two, and four weeks via microradiography/microdensitometry, and a statistically significant dose-response was obtained between non-F and F as well as between 1000 and 2500 ppm F pastes, i.e., as per the three-year clinical trial data. Hence, the model's suitability for pre-clinical screening was confirmed. It has also been used in caries microbiological studies, in root caries investigations, and currently in chewing gum cariogenicity experiments. PMID- 1592975 TI - An intra-oral single-section demineralization/remineralization model. AB - This paper reviews the use of our intra-oral crown single-section model for the evaluation of in situ demineralization and remineralization. The model uses normal, healthy adults who are in need of a gold crown. A slot is placed in the working crown which can hold 3-4 single sections. A typical experiment would use an enamel lesion, root lesion, and sound root section which are characterized with polarized light microscopy and/or microradiography prior to insertion in the crown. After the experimental regimen, the sections are removed and re characterized for any changes. The model has been used to evaluate mineral changes from the use of fluoride dentifrices and rinses, chewing gum, and food sequencing. The advantages of the model system are the before-and-after measurements on the same section, a natural plaque formation, interaction with saliva, episodic demineralization and remineralization, no bulky appliances, and the use of reasonable time frames. This model, therefore, reduces the artificiality of the in situ study to a great extent and appears to be a useful predictor of demineralization/remineralization interactions. PMID- 1592976 TI - Assessment of the effects of dentifrices on plaque acidogenesis via intra-oral measurement of plaque acids. AB - Dionex ion chromatography was used for identification and quantification of the plaque acids (formate, lactate, acetate, and propionate) formed in vivo following a sucrose rinse. Consistent with other literature reports, lactate and acetate were the predominant acid species generated by plaque. This micro-analytical technique was used for investigation of the effects of dentifrice formulations containing NaF, xylitol, or NaF/xylitol on plaque acid metabolism. Neither a single nor multiple exposures (three times daily for one week) to the experimental dentifrices significantly altered the profiles of the individual acids or total plaque acidity relative to the placebo dentifrice. The lack of an effect of fluoride and xylitol on plaque acid metabolism is attributed to the variability of dental plaque and the low concentrations of active ingredients reaching the plaque. However, we believe that, with further improvement in sampling technique and study design, this approach may prove useful for the study of the effects of active ingredients (i.e., anticaries agents) on plaque acidogenesis. PMID- 1592977 TI - Reduction of intra-oral demineralization of enamel after single exposures to sodium fluoride. AB - Studies demonstrated the effects of single rinses with low concentrations of NaF on the intra-oral demineralization of enamel. Blocks of bovine enamel were covered with Streptococcus mutans IB1600, mounted in palatal appliances, and worn in the mouths of volunteers for specified times. Subjects rinsed with solutions of NaF, with or without sucrose. Demineralization was determined as changes in iodide penetrability (delta Ip) of the enamel, while the pH and F of the streptococcal plaque, and enamel F, were determined with ion-specific electrodes. Delta Ip was reduced by about 80% (from 14.5 +/- 2.7 to 2.8 +/- 2.3 units) when 250 micrograms F/mL was added to the sucrose rinse. Corresponding plaque pH's were 4.1 +/- 0.5 and 4.2 +/- 0.3, consistent with a lack of effect on bacterial acidogenesis. Protection against mineral loss was concentration-dependent. Administration of sucrose at different times after NaF revealed that the effect of F persisted for at least 60 min. Analyses of plaque F demonstrated an initial elevation and concentration within the cells, followed by a drop to stable, baseline values. Enamel F increased slowly to almost 500 micrograms/g enamel after 105 min. The protective effect of F appeared to be manifested in two stages, the first related to a high plaque F and the second to F that became incorporated into the enamel. Analysis of the data suggested that F was transferred from plaque to enamel during the experimental period. PMID- 1592978 TI - An improved intra-oral enamel demineralization test model for the study of dental caries. AB - The intra-oral enamel demineralization test (IEDT) was introduced by Brudevold et al. (1984). This caries model involves human subjects wearing palatal appliances each holding eight bovine enamel blocks covered by a bacterial cell layer prepared by the harvesting of cultures of Streptococcus mutants (test plaque). The original model used the iodide permeability test for assessment of the extent of demineralization of bovine enamel blocks resulting from acid production by the test plaque after dietary substrate challenge. The IEDT model has been expanded and improved by us in the following ways: (1) Based on encouraging findings from an in vitro study (Zero et al., 1990), the surface microhardness test has been adopted to measure the extent of demineralization occurring at three sites on the enamel blocks corresponding to an area over which the effective plaque thickness is 0.5, 1.5, and 2.5 mm; (2) intra-oral pH of the test plaque is measured by means of a Beetrode miniature pH electrode at baseline, then at five, 10, 15, 30, and 45 min after the start of a test; (3) plaque samples are collected at the end of a test and analyzed for organic acid content by means of HPLC; (4) the bacterial test challenge has been expanded to include different cariogenic bacteria which are grown under various growth conditions. The improved model has the capability of studying fundamental aspects of the caries process, namely, the relationships among dietary substrate challenge, plaque pH change, plaque organic acid profiles, microbial virulence properties, and enamel demineralization. Furthermore, the model has the potential for use in more applied research on caries-preventive agents such as fluoride. PMID- 1592979 TI - Importance of model parameters in the assessment of intra-oral remineralization. AB - Since the introduction of the Intra-oral Cariogenicity Test by Koulourides et al. (1974), many groups around the world have been developing and using intra-oral models to test new caries-preventive products, as well as to study physiological processes in the oral cavity. In spite of the large numbers of papers reporting these methods, very little research has been done to determine the importance of the many variable parameters which influence the performance of these models. Among these, the following can be identified: (a) panelist criteria, (b) the use of sound vs. pre-demineralized enamel of human or bovine origin, (c) the use of gauze or a recess to accumulate plaque, (d) the method to create incipient lesions, (e) the duration of the experiment, (f) the number of panelists required for statistical significance to be obtained, (g) the assessment techniques for mineral and/or fluoride uptake/loss, and (h) the choice of contralateral, 'cross over', or 'monadic' experimental designs. Our results, supported by data from the literature, indicate that the choices made with respect to these parameters are of paramount importance in determination of the outcome of the respective study. PMID- 1592980 TI - The comparative sensitivity of intra-oral, in vitro, and animal models in the 'profile' evaluation of topical fluorides. AB - The development of predictive and rapid methods for the assessment of the anticaries activity of topical fluorides has been a long-standing objective of caries researchers. These methods can provide useful benefits in a number of applications, ranging from the identification of novel agents to progress into clinical testing to the regulatory screening of commercial product variations. In the latter applications, combinations of test methods (so-called profiles) are used by manufacturers to prove that changes in formulations do not alter the efficacy of the products. Historically, combinations of in vitro and animal models have been used for basic research as well as for profile testing purposes; however, in recent years, the use of intra-oral or in situ models has increased. In this paper, in vitro, animal, and in situ methods are reviewed in terms of the historical basis for their development, protocols currently used in testing, and the primary advantages and limitations of each as applied to 'profile' applications. Recommendations are provided concerning circumstances for the appropriate use of modern test methods in formulation screening. PMID- 1592981 TI - Intra-oral models for studying de- and remineralization in man: methodology and measurement. AB - A wide range of different methodologies and measurement techniques has been employed in laboratories around the world for the study of de- and remineralization of enamel and dentin in intra-oral systems. These different approaches are summarized and discussed in relation to the nature of the different research questions to be studied by means of the intra-oral model. PMID- 1592982 TI - Statistical considerations related to intra-oral studies. AB - Intra-oral studies use caries models from which conclusions are drawn concerning the caries process in the clinical environment. Recently, attention has been drawn to the issue of proper analysis and interpretation of the data from such studies, with particular emphasis placed on a consideration of the role such studies can and should play as a component of product claim submissions to the American Dental Association (ADA). This presentation discusses a number of issues relevant to this consideration, including the validity and reliability of the intra-oral modeling process, the relationship between these concepts and the requirements imposed by the ADA Guidelines for superiority and equivalence claims, and a brief enumeration of several other statistical issues which ought to be considered in the handling of data from such studies. PMID- 1592983 TI - Technical advances in intra-oral model systems used to assess cariogenicity: experimental design and analysis (reactor paper). AB - In situ cariogenicity-testing models must show evidence of compliance with valid clinical parameters, and this has been achieved with respect to pyrophosphate-, monofluorophosphate-, and zinc citrate trihydrate-containing dentifrices, where earlier in vitro studies failed to predict clinical efficacy. Parameters for validity testing should include the use of enamel fluoride uptake, plaque and/or saliva fluoride assessments, re-/demineralization assays of appliance-borne enamel slabs or slices, and plaque microbial, biochemical, and pH studies. Model reliability must be capable of withstanding repeat calibration experiments where the dosage, frequency of application, and/or duration of exposure to a new product may be varied. Furthermore, the number of enamel slabs/slices carried per appliance (and the number of artificial caries lesions per enamel insert) requires to be defined. Such studies should be repeated, but whether in the same or different subjects, or with or without cross-over, has to be determined. However, the capability of reproducing a clinically proven dose-response is essential. Models must be sensitive enough to detect changes in any test product F-concentration, but only equivalence claims should be permitted. Thus, superiority cannot be established, since accuracy may not be assumed beyond the upward limits of a clinically validated range. Finally, models should not be so exclusive in design as to preclude independent verification of their findings. PMID- 1592984 TI - Patient selection and appliance design in intra-oral models. AB - The conclusions derived from in situ studies are influenced by the choices made with respect to parameters of the intra-oral model systems. In an attempt to reach a consensus, this paper considers the variables (a) selection of panelists and (b) appliance design. On both topics, a short review of available systems is given. The objectives of the intra-oral study may vary from the determination of oral physiological parameters to assessment of the effects of caries-preventive treatments. This objective is a factor influencing the choice of experimental conditions. Recommendations for panelist selection and appliance design are given for different types of studies. It is concluded that relatively little information is available about the effects of individual parameters on the performance of a model. Therefore, for an assessment of caries-preventive effectiveness, an intra-oral model should be validated against clinical trials. In addition, conditions should be chosen such as to limit the degree of artificiality of the model. PMID- 1592985 TI - Reactor paper concerning patient selection and appliance design in intra-oral models. AB - Patient selection and appliance design are important factors in the development of intra-oral models. Adults, rather than children, are recommended as panelists due to their similarity to children in response to fluoride for caries prevention, greater likelihood of compliance with all study requirements, and greater availability for appointments. It may be desirable for additional factors -including the presence of cariogenic micro-organisms and the characteristics of their saliva with regard to remineralization--to be used in the selection of panelists. Cross-over test designs may be desirable to minimize the impact of these variables as well as of dietary differences. Appliances should be designed to approximate the normal oral conditions to the maximum extent possible. Intra oral models should be capable not only of detecting the effects of clinically proven fluoride treatments but also of detecting fluoride dosage responses. PMID- 1592986 TI - Hard-tissue substrates for evaluation of cariogenic and anti-cariogenic activity in situ. AB - Hard-tissue substrates include primarily human and bovine enamel and human dentin. They have been used for in situ studies in a natural or sound condition, as well as flattened or containing an in vitro-formed caries-like lesion. Human enamel and dentin are generally the substrates of choice for studies of coronal and root-surface caries, respectively, but bovine enamel appears to offer a suitable alternative for many studies of enamel caries. Substrates with caries like lesions will respond more rapidly to changes in the intra-oral mineral equilibrium and will allow both demineralization and remineralization to be determined. Findings from some studies suggest that caries-like lesions may respond somewhat differently, depending upon the degree of mineralization of the surface layer. Because in vitro findings with dentin show it to be significantly more soluble in acid than enamel, results from a study that used dentin may not be directly applicable to enamel. Both enamel and dentin substrates can be used in thin-section models. Hard-tissue substrates can also differ, depending upon their intra-oral location. Locations that result in the accumulation of plaque will behave differently from those that are plaque-free. So that plaque would accumulate, substrates have been placed approximally, beneath a fabric or steel mesh, in a protected trough, beneath a metal band or within a depression on the buccal surface. For studies requiring a determination of both demineralization and remineralization, human enamel or dentin containing a surface-softened caries like lesion and covered with a uniform natural plaque are the substrates of choice. PMID- 1592987 TI - Intra-oral models: comparison of in situ substrates. AB - Numerous intra-oral caries models have been designed for clinical and mechanistic purposes. Several factors--such as human vs. bovine enamel, sound vs. demineralized tissues, lesion type, dentin vs. enamel, the severity of the cariogenic challenge, and the microflora--may influence the reactivity of the hard tissue and hence lesion development and progression. Some models use unextracted teeth and are true in vivo models, whereas in situ models are based on hard-tissue substrates in the form of slabs or sections. Models producing a moderate cariogenic challenge usually show a fluoride dose response. However, caries is increasingly becoming a problem limited to some high-risk patients and to lesions located to areas where severe challenges exist (e.g., fissures and pits). There is thus need for models that could mimic such situations. One of the requirements for intra-oral models producing severe cariogenic challenge conditions should probably be that it should be able to demineralize fluorapatite. A challenge for future caries research is to develop agents that have a better clinical effect in fissures and pits than those presently available. Because, in the past, much emphasis has been placed on remineralization of artificial lesions, more research on the demineralization process should be performed in the future, since this may give improved clinical effects. Ideally, an intra-oral caries model should take into account as many of the natural oral conditions as possible and minimize the degree of artificiality. PMID- 1592988 TI - Demineralization and remineralization evaluation techniques. AB - This paper compares the experimental techniques utilized to assess the de- or remineralization of enamel or dentin in intra-oral studies. In in situ studies, it is important for one to know how much mineral has been lost or gained, and where the loss or gain occurred. The main emphasis in this paper is on techniques suitable for direct or indirect mineral quantification. The measuring techniques considered are microradiography, iodine absorptiometry, various microhardness tests, polarized light, light-scattering, iodide permeability, and wet chemical analysis. The various techniques are compared concerning suitability for the determination of mineral content in vol% (or wt%), mineral changes in vol% micron (or kg.m-2), and mineral distributions. Furthermore, sample preparation, the importance of protein penetration, nominal mineral loss range, the estimated mineral loss threshold, and the applicability to dentin are compared and considered. It is concluded that, although more than ten techniques are available for the measurement of changes after de- or remineralization in situ, transverse microradiography is the most practical technique for the direct and quantitative measurement of mineral content, mineral changes, and mineral distributions. Cross sectional microhardness testing and light-scattering are also practical indirect techniques for quantitative mineral loss (or gain) determination in intra-oral studies. PMID- 1592989 TI - Demineralization and remineralization evaluation techniques--added considerations. AB - Methods used for the analysis of tooth de- and remineralization include techniques with various degrees of sophistication and quantitative capabilities, ranging from direct measures of mineral gain/loss (e.g., microradiography) to indirect measures (e.g., iodide permeability) of changes in tooth mineral properties. In all instances, the capabilities of methods for accurate determination of changes in tooth mineral properties are affected by procedures used in the preparation of specimens for analysis, the magnitude of change taking place in the test (vs. the detection limits of the techniques), and protocols for specimen analysis. In specific instances, such as in the case of dentin, unique specimen-handling and analysis procedures must be used to prevent artifacts. The choice of techniques for the assessment of de- and remineralization depends strongly upon study protocols and laboratory capabilities; however, 'quantitative' measures of mineral gain and loss are possible only if direct chemical or radiographic techniques are used. Either radiographic, cross sectioned microhardness or polarized light can be used for the determination of lesion depth. Porosity, light-scattering, and surface microhardness are indirect techniques which complement direct measures of mineral gain and loss. Whatever methods are used in the analysis of de- and remineralization, researchers must take care to differentiate accurately among the quantitative capabilities of techniques used in analysis. PMID- 1592990 TI - Intra-oral models to assess cariogenicity: evaluation of oral fluoride and pH. AB - The main purpose of this paper is to review the various methods used for evaluation of fluoride retention in saliva, plaque, and enamel following application of topical anti-caries treatments such as F dentifrices and F mouthwashes. Such methods monitor delivery of fluoride to the site of action, the mouth, and so can be regarded as assessing potential for treatment action. It is concluded that intra-oral fluoride measurements are appropriate to support bioequivalence claims for anti-caries treatments, provided that particular chosen methods have been calibrated against clinical data. Studies purporting to show superiority are of interest mechanistically, but links to caries are not sufficiently understood to define superiority claims. A wide variety of methods has been used for determination of the fluoride content of enamel. Of these, well established methods such as the micro-drill and acid-etch procedures are appropriate for routine comparative testing, whereas sophisticated instrumental techniques such as SIMS are more appropriate for detailed mechanistic studies. Intra-oral pH measurements are also relevant to many topical treatments. Single site determinations in plaque are preferred, but for comparative studies non specific determinations may be adequate. PMID- 1592991 TI - A quantitative comparison of methods measuring fluoride in solutions or in enamel. AB - Fluoride in solution is most usually measured with the ion-specific electrode, although a few other methods are available. The electrode can be used in a straightforward manner, its lower concentration limit may be extended by special methods such as the standard addition of fluoride, or microdiffusion methods may be used to extract fluoride from the sample and concentrate it in base. Specifications of all methods are tabulated. A choice of method depends on the requirements in terms of specifications but also on the personal experience of the investigator and the required robustness. Microdiffusion of some kind is preferable for concentrations below 5 mumol/L or when electrode-interfering molecules such as proteins are present in rather high concentrations. Fluoride in enamel may be determined by removal of layers by etching, abrasion, or microdrilling, followed by dissolution of the layer removed. Specifications of depth and area resolution are tabulated. Alternatively, probing methods of a physical nature can be used. These methods require sophisticated instruments that are not widely available. Some of them are destructive, others are not. All but one require exposure to vacuum. However, most of them combine a very good sensitivity with a very good resolution in depth and/or measured area. Therefore, their use in research (requiring cooperation with instrument specialists/owners) may well be worth the effort. PMID- 1592993 TI - Consensus conference on intra-oral models: experimental design and analysis. PMID- 1592992 TI - Interim report of the ad hoc committee for the consideration of statistical concerns related to the use of intra-oral models in submissions for product claims approval to the American Dental Association. AB - Subsequent to the American Dental Association Symposium on Intra-oral Studies, held in Chicago in September, 1990, the Council on Dental Therapeutics decided that further consideration should be given to statistical issues relating to intra-oral models. The authors accepted the request of Council staff to assist in the development of Guidelines concerning the validity, reliability, and combinability of data obtained from these models. The ensuing work in this area, which began in the fall of 1990 and has continued to date, has thus far focused on the tissue of validity. The purpose of the present paper is to provide the interested community at large with an update on the progress made thus far, and to provide some perspective as to where all of the work in this area may eventually be leading. It is anticipated that a more comprehensive and definitive report will be produced at the completion of this process. PMID- 1592994 TI - Consensus conference on intra-oral models: patient selection, appliance design, and substrate. PMID- 1592995 TI - Consensus conference on intra-oral models: evaluation techniques. PMID- 1592996 TI - Rejuvenation. From hair to hands. PMID- 1592997 TI - Stump the experts. PMID- 1592999 TI - Hair transplantation in females. AB - Hair transplantation in females, to thicken discrete areas of thinning, reconstitute a hairline, or cover scars from previous facial surgery, is a viable treatment option. Techniques dealing with hair transplantation in females are discussed. PMID- 1592998 TI - Recurrence rates of treated basal cell carcinomas. Part 3: Surgical excision. AB - This is the third report in a series that reviews the experience in the Skin and Cancer Unit, from 1955 through 1982, with the treatment of basal cell carcinomas (BCCs). It concerns 588 previously untreated (primary) BCCs removed by surgical excision. The cumulative 5-year recurrence rate was 4.8%. This is a statistically significant lower recurrence rate (P = .034) than 135 previously treated BCCs that had a re-recurrence rate of 11.6%. For the primary BCCs, multivariate analysis showed that location on the head (P = .010) and being male (P = .004) were independent risk factors for recurrence. The patient's age, the duration of the BCC, its maximum diameter, or the time span (1955-1963, 1964-1972, 1973-1982) in which it was treated did not significantly affect the recurrence rate. The 5 year recurrence rate for BCCs excised from various anatomic sites were as follows: 1) neck, trunk, and extremities = 0.7%; 2) head--less than 6 mm in diameter = 3.2%; 3) head--6 to 9 mm in diameter = 8.0% (treated since 1964 = 5.2%); and 4) head--10 mm or more in diameter = 9.0%. Surgical excision is a highly effective method for removal of BCCs, and achieved a good to excellent cosmetic outcome in about 85% of the recurrence-free treatment sites. PMID- 1593000 TI - A new modification for preparing tissue blocks for cryostat sectioning. AB - A modification of the Carter method for preparing tissue blocks for cryostat sectioning is presented. One problem with the Carter method is that tissue edges occasionally freeze above the plane of the smooth cryostat disk. My modification avoids this problem by gradual liquid nitrogen cooling of the disk. This enables all tissue edges to be applied to the smooth disk surface until freeze adherence occurs. PMID- 1593001 TI - A new instrument for the expedient production of minigrafts. AB - In the past, minigrafts have been made by either quartering 4.5-mm punchgrafts, halving 4.0-mm grafts, or a variety of other similar methods. These techniques notoriously require a prodigious amount of time for harvesting and preparation of the minigrafts. This article presents an instrument and technique that significantly cuts down on both harvesting and preparation time. Besides these important factors, the author has found the shape of these minigrafts to be more similar to the shape of an incisional slit. There has also been noted better healing at the donor site, less wasting of viable hair follicles, and improved control over the number of hairs per minigraft. PMID- 1593002 TI - Running vertical mattress suture. AB - Various types of running sutures have been described for use in dermatologic surgery. The running vertical mattress suture is a time-saving technique that can be used alone or in combination with any running-suture technique. It is useful for wound eversion, providing hemostasis, and closing wounds under mild tension. PMID- 1593003 TI - Macrocheiloplasty. Principles and techniques. AB - Enlarged configurations of one or both lips from hereditary and racial differences are common phenomena. Congenital anamolies and acquired malformations are more unusual. The author reviews the principles of lip size reduction, and demonstrates photographically the serial steps necessary to accomplish that goal on the lower lip. PMID- 1593004 TI - Magnetic resonance imaging evaluation helps to delineate a recurrent skin cancer present under the skin flap. AB - A case of recurrent squamous cell carcinoma under a skin flap as confirmed and delineated by magnetic resonance imaging (MRI) is described. This report illustrates a potentially new indication for MRI in clinical dermatology, namely, to define skin cancer recurrences under skin flaps and grafts and to determine the extent of underlying tissue involvement. The cost-effectiveness of MRI and the use of gadolinium, an MRI contrast agent, in the evaluation of skin tumors are also addressed. PMID- 1593005 TI - Drug interactions in dermatologic surgery. AB - Intravenous sedation is a popular method of anesthesia in outpatient cosmetic surgery. To ensure a successful surgical outcome, awareness of potential interactions between intravenous agents and patient medications is essential. The more commonly used intravenous drugs are reviewed, with particular emphasis on their side-effects and potential for drug interactions. PMID- 1593006 TI - Cumulative sunlight exposure and the risk of developing skin cancer in Florida. AB - Epidemiologic evidence suggests that the risk of developing skin cancer is higher in certain geographic regions where sunlight is excessive. Even in such high risk regions, two distinct populations of long-term residents exist: people with, and people without skin cancer. We have compared the quantitative lifetime sunlight exposure between 11 nonmelanoma skin cancer patients who have lived in South Florida for 23.7 +/- 5.1 years and 9 age-matched normal, healthy individuals who have lived in South Florida for 23.4 +/- 4.1 years. An estimation of personal cumulative sunlight exposure was determined for each subject from data collected through detailed interviews. We found that there was no detectable, significant quantitative difference in cumulative sunlight exposure during life between these two groups. Because these individuals had previously been phenotyped for the effects of ultraviolet-B (UVB) radiation on induction of contact hypersensitivity, our results suggest that UVB-susceptibility may be a better indicator of skin cancer risk than cumulative lifetime sunlight exposure. Thus, although there is little doubt that sunlight exposure is an important factor in the development of skin cancer, our results emphasize the importance of host genetic factors in the pathogenesis of this disease. PMID- 1593007 TI - Re: Microsurgical treatment of nasolabial and glabellar wrinkles. PMID- 1593008 TI - Re: A preference for natural rounded defects requiring rounded flaps over iatrogenic hexagonal defects requiring rhomboid flaps for rounded alopecia. PMID- 1593009 TI - Genetic localization of DDT resistance in Drosophila melanogaster (Diptera: Drosophilidae). AB - Adult resistance to DDT conferred by various regions of the second chromosome of a DDT-resistant strain of Drosophila melanogaster (Meigen) was analyzed using the quantitative genetic method of Thoday and a topical test procedure. Resistance was localized in a small region near and to the left of cn. Both the genetic method and the topical test technique were effective. Results are consistent with the idea that the number of loci responsible for insecticide resistance in D. melanogaster is not large. PMID- 1593010 TI - Measuring cypermethrin resistance in the German cockroach (Orthoptera: Blattellidae). AB - Cypermethrin resistance in the German cockroach, Blattella germanica (L.), was assessed by tests of surface contact and topical application. Topical application provided the most sensitive measure of resistance in a field strain. The resistance ratio (RR) measured by topical application was 122.6 for cypermethrin at LD50. As measured by surface contact, the resistance ratio at KT50 was 2.9. Differences between the walking movement of cockroaches of susceptible (VPI) and field (RHA) strains on deposits of cypermethrin influenced KT50 values. A bioassay with unrestricted movement resulted in RHA strain cockroaches accumulating a larger dose on the tarsal pads and subsequent reduction of the resistance ratio at KT50. Less walking by the VPI strain resulted in less insecticide accumulation on their tarsal pads. On a bioassay in which movement was restricted, the amount of insecticide accumulating on the tarsi was equalized, resulting in an increased resistance ratio at KT50. Differences in susceptibility were more accurately measured when the two strains were topically treated (either on the thorax or the tarsal pads) with known doses of insecticide. PMID- 1593011 TI - Selection of dieldrin-resistant strains of Lucilia cuprina (Diptera: Calliphoridae) after ethyl methanesulfonate mutagenesis of a susceptible strain. AB - After ethyl methanesulfonate (EMS) mutagenesis of a susceptible strain (SWT), selective screening of Lucilia cuprina (Wiedemann) resulted in four strains that were resistant to the insecticide dieldrin. Concentrations used for selection were greater than LC99 of susceptible phenotypes. No resistant variants were screened from the standard laboratory strain (SWT) not treated with EMS. The resistance phenotypes of the four resistant strains were similar to each other and to that of a field-selected resistant strain. The genetic basis of resistance is monogenic in all strains and the data are consistent with the same locus, Rdl, determining resistance status in each strain. The Rdl locus maps to chromosome V, approximately 3.5 map units distal to the Sut locus. Dieldrin resistance may be caused by less effective blocking of insect neuronal GABA receptors by the chemical in resistant strains. The data indicate that the evolution of resistance to an insecticide in the field may be constrained by a limited number of genetical and biochemical options if a monogenic response is selected for and that the spontaneous mutation rate to the Rdl allele is less than 1 in 10(6) in the laboratory. PMID- 1593012 TI - Susceptibility and behavioral response of red imported fire ant (Hymenoptera: Formicidae) to selected entomogenous nematodes (Rhabditida: Steinernematidae & Heterorhabditidae). AB - Pathogenicity of infective juveniles of selected Steinernema spp. and Heterorhabditis spp. toward developing and reproductive stages of the red imported fire ant, Solenopsis invicta Buren, was tested under laboratory conditions. At 10(3)-10(5) infective juveniles per Petri dish, mortality of reproductive larvae, pupae, and alates ranged from 28 to 100% at higher doses after 96 h at 23-25 degrees C. Steinernema carpocapsae All was the most consistent species tested; this nematode caused mortality of fire ant larvae, pupae, and alates of 82-94, 64-96, and 38-99%, respectively. Although not susceptible to nematode infection, worker ants vigorously preened nematodes from brood, alates, and themselves. In a field study, S. carpocapsae (5 x 10(6) and 2 x 10(6) drench, 2 x 10(6) infective juvenile infection) was applied to active fire ant mounds in 3.8-liter suspensions. Hydramethylnon (75 ml), a water drench, a water injection, and untreated fire ant mounds were marked and treated. Overall activity in mounds treated with nematodes of hydramethylnon ranged from 40 to 48%. Satellite mound activity accounted for 32-44% of overall activity in mounds treated with nematodes 2 wk after treatment. However, 6 wk after treatment, activity in mounds treated with hydramethylnon was 44%; activity of mounds treated with nematodes ranged from 52 to 80%. Satellite mound activity accounted for 0-24% of overall activity. Whereas a soil drench of S. carpocapsae showed potential as a control method for the red imported fire ant, colony relocation after nematode treatment could limit overall efficacy unless application techniques are developed to overcome or take advantage of the movement. PMID- 1593013 TI - Effects of four monoterpenoids on growth and reproduction of the German cockroach (Blattodea: Blattellidae). AB - The effects of the monoterpenoids d-limonene, linalool, beta-myrcene, and alpha terpineol on the growth and development of the German cockroach Blattella germanica (L.) were examined. We evaluated the chemicals' attractiveness in cockroach diet, quantified growth effects induced by monoterpenoids, examined embryotoxic properties of the compounds, and examined their effects on reproduction when administered by oral, topical, and vapor routes of entry. Untreated diet was significantly preferred compared with diet treated with high levels of d-limonene, linalool, and alpha-terpineol. The threshold for acceptance was between 1 and 10% (AI). All four monoterpenoids significantly influenced the days required by nymphs to reach the adult stage; in general, higher monoterpenoid concentrations in the diet were associated with a reduction in the days required by nymphs to mature. Application of high doses of d-limonene or linalool to oothecae of gravid female cockroaches significantly decreased the probability of young emerging from them but did not affect female mortality. Feeding on diet treated with monoterpenoids during nymphal development and through the early, premating period of the adult stage did not significantly influence numbers of broods produced per pair, numbers of offspring per brood, days required to produce a brood, total offspring produced by a pair, or female life span. Topical applications of linalool, beta-myrcene, or alpha-terpineol at near lethal rates to adult cockroaches before they mated had no significant influence on the reproductive parameters examined. A single exposure to sublethal levels of monoterpenoid vapors before mating had no significant influence on any reproductive parameters examined. PMID- 1593014 TI - Susceptibility of house flies (Diptera: Muscidae) and five pupal parasitoids (Hymenoptera: Pteromalidae) to abamectin and seven commercial insecticides. AB - Assays of five commercial insecticides applied as residual sprays at label rates to plywood indicated the most toxic insecticide overall for pteromalid parasitoids of house flies, Musca domestica L., was Atroban (permethrin), followed by Ciodrin (crotoxyphos), Rabon (tetrachlorvinphos), Ectrin (fenvalerate), and Cygon (dimethoate). Insecticide-susceptible house flies were susceptible to all five insecticides (mortality, 62-100%). Flies that were recently colonized from populations on dairy farms in New York were susceptible only to Rabon. Urolepis rufipes (Ashmead) was the most susceptible parasitoid species overall to these insecticides, followed by Muscidifurax raptor Girault & Sanders, Nasonia vitripennis Walker, Pachycrepoideus vindemmiae (Rondani), and Spalangia cameroni Perkins. Compared with susceptible flies, newly colonized flies showed moderate resistance to avermectin B1a (abamectin). Abamectin was more toxic to all of the parasitoids except N. vitripennis and S. cameroni than to newly colonized house flies when exposed for 90 min to plywood boards treated with 0.001-0.1% abamectin. Space sprays with Vapona (dichlorvos) killed all of the parasitoids and susceptible flies and 64% of the newly colonized flies when insects were placed directly in the path of the spray; mortality was substantially lower among flies and parasitoids protected under 5 cm of wheat straw. Space sprays with Pyrenone (pyrethrins) killed greater than 86% of all insects exposed to the spray path except for the newly colonized flies (1% mortality); mortality of insects protected under straw was low (less than 12%) except for S. cameroni (76%). Because responses of the five parasitoids to the different insecticides varied considerably, general conclusions about parasitoid susceptibility to active ingredients, insecticide class, or method of application were not possible. PMID- 1593015 TI - Persistence of sterile screwworm (Diptera: Calliphoridae) flies at a release site. AB - Studies to determine the persistence of released, sterile screwworms, Cochliomyia hominivorax (Coquerel), were conducted in Belize, Central America, in 1987-1988. A total of nine releases were made, each consisting of 4,000 females marked with a fluorescent dust. Previous similar studies with baited fly traps indicated that flies died or dispersed from the release site within 3-4 d. For this study, flies were recaptured at sentinel animals. Recapture rates varied greatly between releases, a result that was not correlated with any weather parameter. The pattern of recapture indicated a sharp drop in the released population after 9-10 d, with a few flies persisting in the release area for up to 3 wk. The results suggest that survival of released sterile flies is comparable with estimated survival rate and life span of wild, native flies. PMID- 1593016 TI - Gel extenders in larval diet of Cochliomyia hominivorax (Diptera: Calliphoridae). AB - Larvae of the screwworm, Cochliomyia hominivorax (Coquerel), were reared on meridic diets containing ground corncob material (grit) in test 1 and the cob grit or sawdust in test 2 to reduce or replace the amount of an expensive synthetic copolymer gelling agent. Biological parameters for the tests included pupal yield (total number), pupal weight (size), pupal malformation, adult emergence, adult malformation, egg weight, and egg hatch to assess for any significant differences. In the first test, larval propagation was successful for five consecutive generations on 24 of an original 37 formulations. Results indicate that a minimum concentration of 4% of the cob grit is needed to reduce the gel by 50%; at least 8% concentration is needed to reduce the gel by 80%; and at least 12% concentration is needed to replace the gel completely. In the second test, the larvae were successfully propagated for five consecutive generations when the copolymer gel was reduced by 50 or 75% in the diet by using either sawdust or the no. 60 cob grit size. The cost savings and applications of use of sawdust or the cob grit incorporated into the larval diet can be beneficial to a mass-production screwworm program. PMID- 1593018 TI - Intralesional human leukocyte interferon treatment alone or associated with IL-2 in non-AIDS related Kaposi's sarcoma. AB - Patients with classical European Kaposi's sarcoma were treated by intra- and peritumoral injections of human alpha leukocyte interferon (IFN) (12 cases) or, alternatively, with IFN and naturally synthesized IL-2 (8 cases). All the patients were HIV negative with tumors which had been present for at least six months. In each patient, one tumor received 1 ml (50,000 IU) IFN alone or alternatively associated with 1 ml IL-2 twice a week for 4-6 weeks; another nodule situated 10-12 cm away was considered as a control and remained uninjected. The clinical follow-up revealed that, in the same patient in the same anatomical area, the treated nodule was cured in all the investigated cases; the untreated one was not. These data strongly suggest that IFN is the factor responsible for the involution and final cure of these Kaposi tumors treated by perilesional inoculations. Association with IL-2 (and certainly also other interleukins) increases the beneficial clinical activation of the tumor involution. Histological examination showed that important histopathological changes occur in the treated nodules: complete disappearance of the Kaposi's aspect, fibrosclerous modifications progressively replacing the fibroblasts characteristic of Kaposi's sarcoma, abundant infiltrations of leukocytes, especially lymphocytes and necrotic patches, often with hemorrhagic centers. IL-2 association seems to especially induce this last type of histological phenomenon. PMID- 1593017 TI - Evaluation of field propagation of Muscidifurax zaraptor (Hymenoptera: Pteromalidae) for control of flies associated with confined beef cattle. AB - The parasitic wasp Muscidifurax zaraptor Kogan & Legner was mass-reared in the field to control house flies, Musca domestica L., on two Nebraska beef cattle confinements. About 50,000 freeze-killed house fly pupae were exposed to a single release of M. zaraptor in the field. Placement of six additional cohorts of 50,000 freeze-killed pupae at the release sites at 2-wk intervals resulted in a mean parasite emergence of 56.4% over the study period. Mean fly mortality of 37.3 and 25.9% occurred in sentinel pupae placed around the perimeter of two release sites, compared with 3.9% for two control sites. We demonstrated a negative correlation between host reduction in sentinel cohorts and distances the cohorts were placed from parasite release sites. However, data indicated that other environmental factors also influenced the success of M. zaraptor in locating sentinel hosts. Correlation between mortality in sentinel pupae and numbers of parasites released was not evident. Temperatures above approximately 28 degrees C appeared to reduce the effectiveness of M. zaraptor. PMID- 1593019 TI - Churg-Strauss syndrome: report of a case without preexisting asthma. AB - A 38-year-old male with no history of asthma, who initially presented with episcleritis and subsequently developed symptoms of systemic vasculitis with marked blood eosinophilia, was diagnosed as having Churg-Strauss syndrome (CSS). Both the patient's skin lesions and pulmonary infiltrates revealed histologically proven vasculitis with predominantly eosinophilic infiltration. All the symptoms of systemic vasculitis except the persisting peripheral neuropathy dramatically improved after corticosteroid was systemically used. Since scattered non asthmatic cases of CSS have been reported recently, and three such patients have died of acute heart failure due to delayed diagnosis, absence of asthma should not be regarded as an absolute criterion for exclusion of the diagnosis of CSS. Earlier recognition of this disease is important, since earlier institution of steroid therapy can prevent the acute onset of fatal cardiac involvement during the course of this disease. PMID- 1593020 TI - The Koebner phenomenon in eruptive xanthoma. AB - A 49-year-old woman with Type V hyperlipidemia had yellow papules smaller than 3 mm in diameter with red haloes on her elbows, shoulder, buttocks, and hands. Two linear lesions composed of papules arising at the sites of skin previously injured by a cat scratch were observed. Histopathological examination of these papules revealed the presence of many foam cells in the dermis which stained positively with oil red O stain. A survey of the literature found only 5 cases of the Koebner phenomenon in xanthoma. PMID- 1593021 TI - Microcystic adnexal carcinoma: a case report with immunohistochemical and electron microscopical examinations. AB - Microcystic adnexal carcinoma (MAC) is an unusual cutaneous neoplasm comprised of pilar and sweat duct structures. We report here a 66-year-old Japanese woman with MAC on her left nasolabial fold with more prominent calcified keratinous cysts than ductal differentiated structures which stained positively for carcinoembryonic antigen (CEA). The clinical appearance and statistical characteristics of MAC are reported to be different from those of other adnexal tumors. Desmoplastic trichoepithelioma (DTE) is the most difficult tumor to differentiate from MAC, unless positive reactivity for CEA in differentiated ductal structures in MAC can be demonstrated. We compare the differences between the clinical, histological, immunohistochemical, and electron microscopical features of DTE and MAC. It seems probable that these differences could be explained by biological differences in the characteristics of the cells from which these tumors originate, hair follicle cells and eccrine sweat cells, respectively. PMID- 1593022 TI - Inoculation lupus vulgaris. AB - An 11-years-old girl with lupus vulgaris on the right buttock following inoculation is described. The diagnosis was formed by the history, morphological characteristics, Mantoux test, histopathology, and was supported by an affirmative response to short course intensive chemotherapy (6 months). This route of infection acquires special significance with the worldwide-spread of HIV infection. PMID- 1593023 TI - The social competence of very-low-birthweight children: teacher, peer, and self perceptions. AB - Whether very-low birthweight (VLBW less than or equal to 1500 gm) children differ from normal birthweight (NBW greater than 2500 gm) children with respect to social (as opposed to intellectual) competence has been a relatively neglected issue. The social competence at school age of 183 VLBW children was therefore compared with that of 183 NBW children born at the same hospital matched for age, gender, social class, parity, and maternal age. A multi-informant, multidefinitional approach to social competence was adopted involving teacher, (same-gender) peer, and self-ratings of the 366 children's levels of social maladjustment, social skill, and peer acceptance. VLBW children from the upper, middle, and lower social classes received significantly higher mean sadness/unhappiness scores (even with IQ covaried) than their NBW counterparts. Mean scores for the VLBW group were also higher for social withdrawal, and lower for both social skill and peer acceptance. Possible antecedents and consequences of such group differences in affect and sociability are suggested. PMID- 1593024 TI - Psychometric vs. attentional correlates of early onset alcohol and substance abuse. AB - Adolescent inpatients with a diagnosis of alcohol abuse (n = 28), nonalcohol substance abuse disorders (n = 15), or psychiatric disorders without substance abuse (n = 46) were examined on measures of attentional, intellectual, and personality functioning. High scores on a personality measure, the Substance Abuse Proclivity Scale (SAP), was the best predictor of substance abuse in general. Alcohol abusers were differentiated from other substance abusers by their increased impairment on the Continuous Performance Test. Adolescents with alcohol abuse did not manifest the types of cognitive impairments associated with chronic alcoholism. These data suggest that certain attentional impairments may be associated with early onset alcohol abuse and that earlier conceptions of the role of attentional impairments in risk prediction for alcohol abuse are supported. PMID- 1593025 TI - Frontal lobe functions in attention deficit disorder with and without hyperactivity: a review and research report. AB - We review 22 neuropsychological studies of frontal lobe functions in children with attention deficit disorder with and without hyperactivity (ADD/+H, ADD/-H). Some measures presumed to assess frontal lobe dysfunctions were not reliably sensitive to the deficits occurring in either form of ADD. Tests of response inhibition more reliably distinguished ADD/+H from normal children. Where impairments were found on other tests between ADD and normal subjects, they were highly inconsistent across studies and seemed strongly related to age of the subjects and possibly to the version of the test employed. Other methodological differences across studies further contributed to the discrepant (LD) and conduct problems, with ADD may be an additional confounding factor in some, though not all, of these studies. In a separate reports. The co-morbidity of other disorders, such as learning disabilities (LD) and conduct problems, with ADD may be an additional confounding factor in some, though not all, of these studies. In a separate study, children with ADD/+H (n = 12) were then compared on frontal lobe tests to three other groups: ADD/-H (n = 12), LD but no ADD (n = 11), and normal children (n = 12) statistically covarying for differences in conduct problems across groups. Most measures did not distinguish among these groups. Both ADD groups made more omission errors on a Continuous Performance Test (CPT) than the normal group. All three clinical groups performed more poorly on the word and interference portions of the Stroop Test. Thus, while both types of ADD share some apparent similarities in deficits on a few frontal lobe tests in this study, the totality of existing findings suggests an additional problem with perceptual-motor speed and processing in the ADD/-H group. PMID- 1593026 TI - Evaluative communications between affectively ill and well mothers and their children. AB - Earlier research suggests that the natural verbal discourse of mothers with their children can be important in clarifying, verifying, and evaluating the behavior in which a child is engaged, in attributing qualities to the child, and in influencing the child's self-perceptions. We investigated the potential influences of parental affective illness (bipolar affective disorder and unipolar depression in contrast to no history of psychiatric illness) on such "labeling" behavior in a sample of 61 mothers and their older (school-age) and younger (preschool-age) children. It was hypothesized that the dispositions characterizing affective illness (specifically, negativity and disengagement) would be reflected in the labeling statements of mothers with a diagnosis as they interacted with their children. Based on videotaped interactions during a visit to a home-like laboratory apartment, labeling statements were identified in terms of speaker and person being labeled ("addressee") and coded (positive, negative, mixed, or neutral) for judgmental and affective quality of the statement and reaction of the addressee. Data were analyzed (a) by family unit and (b) my mother to child statements. The general pattern of findings indicated, in relative terms, an excess of negativity on the part of family members in the bipolar group and a dearth of negative affect for mothers in the unipolar group. Negativity in the bipolar group appeared to be especially likely when the setting involved mothers and two male children. Additionally, findings are discussed in terms of sex differences in vulnerability to depression. PMID- 1593027 TI - Single and combined effects of methylphenidate and behavior therapy on the classroom performance of children with attention-deficit hyperactivity disorder. AB - Twenty-four boys with attention deficit-hyperactivity disorder (ADHD) participating in an intensive summer treatment program each received b.i.d. placebo and two doses of methylphenidate (MPH, 0.3 mg/kg and 0.6 mg/kg) crossed with two classroom settings: a behavior modification classroom including a token economy system, time out and daily home report card, and a "regular" classroom setting not using these procedures. Dependent variables included classroom observations of on-task and disruptive behavior, academic work completion and accuracy, and daily self-ratings of performance. Both MPH and behavior modification alone significantly improved children's classroom behavior, but only MPH improved children's academic productivity and accuracy. Singly, behavior therapy and 0.3 mg/kg PMH produced roughly equivalent improvements in classroom behavior. Further, the combination of behavior therapy and 0.3 mg/kg MPH resulted in maximal behavioral improvements, which were nearly identical to those obtained with 0.6 mg/kg MPH alone. PMID- 1593028 TI - Abrupt vessel closure after directional coronary atherectomy. The U.S. Directional Atherectomy Investigator Group. AB - From October 1, 1986 to December 31, 1989 directional coronary atherectomy was performed during 1,020 procedures (1,140 lesions) at 14 clinical centers. Abrupt vessel closure, defined as a total coronary occlusion or subtotal occlusion associated with clinical evidence of myocardial ischemia, occurred in 43 procedures (4.2%). It developed in the catheterization laboratory in 34 patients, but was delayed 1 to 96 h after directional atherectomy in 9 patients. By univariate analysis the incidence of abrupt closure was higher in directional atherectomy of de novo lesions (p less than 0.001), lesions in the right coronary artery (p = 0.001) and diffuse lesions (p = 0.04). The incidence of abrupt closure tended to be lower in directional atherectomy of saphenous vein grafts as opposed to native coronary arteries (1.6% vs. 4.4%; p = 0.08). Clinical findings during abrupt closure included severe angina in 26 patients, myocardial infarction in 17 patients, hypotension in 5 patients and death in 2 patients. Balloon angioplasty was attempted in 32 patients after abrupt vessel closure. In 16 patients balloon angioplasty resulted in initial resolution of the closure episode, although 1 patient died 96 h after the procedure. Fifteen of 16 patients without initial improvement after balloon angioplasty underwent coronary bypass operation; 9 additional patients with abrupt closure were referred directly for bypass operation. It is concluded that abrupt vessel closure develops relatively infrequently after directional coronary atherectomy. In the absence of severe coronary dissection, abrupt closure after directional atherectomy may be effectively managed with balloon angioplasty in some cases, although coronary bypass operation is often required. PMID- 1593029 TI - Prognostic value of dipyridamole thallium-201 imaging in elderly patients. AB - The prognostic value of intravenous dipyridamole myocardial perfusion imaging has not been studied in a large series of elderly patients. Patients greater than or equal to 70 years of age with known or suspected coronary artery disease were evaluated to determine the predictive value of intravenous dipyridamole thallium 201 imaging for subsequent cardiac death or nonfatal myocardial infarction. Of the 348 patients, 207 were symptomatic and 141 were asymptomatic; 52% of the asymptomatic group had documented coronary artery disease. During 23 +/- 15 months of follow-up, there were 52 cardiac deaths, 24 nonfatal myocardial infarctions and 42 revascularization procedures (percutaneous transluminal coronary angioplasty in 20; coronary artery bypass surgery in 22). Clinical univariate predictors of a cardiac event included previous myocardial infarction, congestive heart failure symptoms, hypercholesterolemia and diabetes (all p less than 0.05). The presence of a fixed, reversible or combined thallium-201 defect was significantly associated with the occurrence of cardiac death or myocardial infarction during follow-up (p less than 0.05). Cardiac death or nonfatal myocardial infarction occurred in only 7 (5%) of 150 patients with a normal dipyridamole thallium-201 study (p less than 0.001). Stepwise logistic regression analysis of clinical and radionuclide variables revealed that an abnormal (reversible or fixed) dipyridamole thallium-201 study was the single best predictor of cardiac events (relative risk 7.2, p less than 0.001). As has been demonstrated in younger patients, previous myocardial infarction (relative risk 1.8, p less than 0.001) and symptoms of congestive heart failure at presentation (relative risk 1.6, p = 0.02) were also significant independent clinical predictors of cardiac death or myocardial infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593030 TI - Are you ever too old to be risk stratified? PMID- 1593031 TI - Midterm outcome of patients with asymptomatic restenosis after coronary balloon angioplasty. AB - Although many patients with restenosis after balloon coronary angioplasty have recurrence of angina, others remain asymptomatic. To assess the clinical implications of asymptomatic coronary restenosis, we analyzed clinical and angiographic characteristics of 277 consecutive patients with restenosis, 133 (48%) of whom were asymptomatic (group I) and 144 (52%) symptomatic (group II). Restenosis was documented 6 to 9 months after the index procedure, or earlier if angina recurred, and was defined as a greater than 50% lumen narrowing (visual estimation). Group I (asymptomatic group) included fewer female (9% vs. 18%, p less than 0.05) and hypertensive patients (38% vs. 56%, p less than 0.005) and more patients with a previous myocardial infarction (48% vs. 28%, p less than 0.05) and single-vessel disease (67% vs. 55%, p less than 0.05). Before angioplasty, symptoms had lasted for a shorter period (10 +/- 25 vs. 23 +/- 42 months, p less than 0.001), ischemia after a recent infarction was a more frequent indication (21% vs. 10%, p less than 0.05) and total revascularization more frequently obtained (74% vs. 63%, p less than 0.05) in group I than in group II patients. Only a normal blood pressure, previous myocardial infarction, single vessel disease and a shorter duration of symptoms were independent correlates of asymptomatic restenosis. No differences were found in stenosis severity before angioplasty (90% in both groups) or after angioplasty (22% +/- 12% vs. 24% +/- 16%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593032 TI - Silent myocardial ischemia after coronary angioplasty: distinguishing the shadow from the substance. PMID- 1593033 TI - Fibrinolytic response during exercise and epinephrine infusion in the same subjects. AB - To determine whether exercise-induced increases in tissue plasminogen activator (t-PA) were related to plasma epinephrine concentration during exercise, 14 healthy men (aged 24 to 62 years) were studied during epinephrine infusions (10, 25 and 50 ng/kg per min) and graded supine bicycle exercise, beginning at 33 W and increasing in 33-W increments until exhaustion. Plasma epinephrine, active and total t-PA, active plasminogen activator inhibitor type 1 (PAI-1) and t PA/PAI-1 complex concentrations were measured at each exercise and infusion level. During epinephrine infusion, active and total t-PA levels increased linearly with the plasma epinephrine concentration (respective slopes [+/- SEM] of 0.062 +/- 0.003 and 0.076 +/- 0.003 pmol/ng epinephrine). During exercise, t PA levels did not increase until plasma epinephrine levels increased, after which both active and total t-PA levels again increased linearly with the plasma epinephrine concentration, but at twice the rate observed with epinephrine infusion (0.131 +/- 0.005 and 0.147 +/- 0.005 pmol/ng, respectively). The t-PA level in blood was directly proportional to the plasma epinephrine concentration during both exercise and epinephrine infusion, suggesting that epinephrine release during exercise stimulates t-PA secretion. In these healthy subjects, active plasminogen activator inhibitor type 1 and t-PA/PAI-1 complex levels were low (41 +/- 11 and 21 +/- 5 pmol/liter, respectively) and did not change significantly during exercise or epinephrine infusion. It is concluded that approximately 50% of the increase in t-PA during exercise is due to stimulated release of t-PA by epinephrine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593034 TI - Effects of diltiazem on recurrent myocardial infarction in patients with non-Q wave myocardial infarction. AB - Diltiazem has been reported to reduce the short-term in-hospital reinfarction rate in patients with a non-Q wave myocardial infarction. In the long-term Multicenter Diltiazem Postinfarction Trial, there were 514 patients with non-Q wave myocardial infarction; 279 patients were randomized to the placebo group and 235 to the treatment group. The average follow-up period was 25 months. There was no difference in baseline clinical characteristics between the two groups. Early reinfarction (less than or equal to 6 months) occurred in 17 patients in the placebo group and in 2 patients in the diltiazem group (p less than 0.001). Late reinfarction (greater than 6 months) occurred in 13 patients in the placebo group and in 14 patients in the diltiazem group (p = NS). Initial and reinfarction electrocardiograms (ECGs) were analyzed by using a coding system that permitted identification of standard anatomic areas involved in the infarction process. Thirty-one of the 46 patients had a localized infarction on index and reinfarction ECGs. In the early reinfarction group, 10 (77%) of 13 infarctions occurred in the same ECG region in which the initial infarction had occurred; all 10 were in patients in the placebo group. Among the 18 patients with late reinfarction, the site of the second infarction was the same as that of the first in 9 patients and differed in 9. There was no difference between the placebo and diltiazem groups with respect to location of the infarction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593035 TI - A study on coronary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina: endothelium-dependent dilation in the resistance vessels. AB - The epicardial coronary artery of patients with variant angina is hyperreactive to the constrictive effect of acetylcholine, but it is not known whether the coronary microvasculature also constricts in response to acetylcholine. Incremental doses of acetylcholine were injected into the left coronary artery of 57 patients with variant angina and with spasm in this artery. By measuring coronary sinus blood flow, coronary hemodynamic status just before angiographic documentation of spasm was examined. Acetylcholine induced spasm in the left coronary artery in all patients. It also decreased the diameter of the nonspasm artery by 36 +/- 19% from baseline. For all patients, coronary sinus blood flow was 89 +/- 38 ml/min at baseline and increased to 104 +/- 61 ml/min during an acetylcholine-induced anginal attack (p less than 0.01). In 10 patients with spasm in both the left anterior descending and left circumflex arteries (that is, multivessel spasm), coronary sinus blood flow decreased from 84 +/- 21 to 52 +/- 26 ml/min (p less than 0.01). In the other 47 patients with spasm in only one of these two arteries (that is, single-vessel spasm), coronary sinus blood flow increased from 90 +/- 41 to 115 +/- 61 ml/min (p less than 0.01) without change in the rate-pressure product. It is concluded that in patients with variant angina, acetylcholine induces spasm and constriction in the epicardial coronary artery, whereas it dilates the resistance vessels presumably through the release of the endothelium-dependent relaxing factor. PMID- 1593036 TI - Influence of coronary bypass surgery on subsequent outcome of patients resuscitated from out of hospital cardiac arrest. AB - The effect of coronary bypass surgery on recurrent cardiac arrest was estimated in 265 patients resuscitated from out of hospital cardiac arrest between 1970 and 1988. From this cohort, 85 patients (32%) underwent coronary bypass surgery after recovery from cardiac arrest and 180 patients (68%) were treated medically. A multivariate Cox analysis was used to estimate the effect of coronary bypass surgery on subsequent survival after adjusting for effects of age, prior cardiac history, ejection fraction, year of the event, history of angina, antiarrhythmic drug use and whether the arrest was related to acute myocardial infarction. The use of coronary bypass surgery had a significant effect in reducing the incidence of subsequent cardiac arrest during follow-up study (risk ratio [RR] 0.48, 95% confidence interval [CI] 0.24 to 0.97, p less than 0.04). There was also a trend consistent with a reduction in total cardiac mortality (RR 0.65, 95% CI 0.39 to 1.10, p = 0.10). These findings suggest that coronary bypass surgery may reduce the incidence of sudden death in suitable patients resuscitated from an episode of ventricular fibrillation. PMID- 1593037 TI - 23rd Bethesda conference. American College of Cardiology: Access to cardiovascular care. Introduction and general principles. PMID- 1593038 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 1: Scope of the problem. PMID- 1593039 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 2: Human and systems resources for cardiovascular care. PMID- 1593040 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 3: The role of the cardiovascular specialist. PMID- 1593041 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 4: Influence of private sector parties on access to cardiovascular care. PMID- 1593042 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 5: Access to cardiovascular care: an international comparison. PMID- 1593043 TI - 23rd Bethesda conference: access to cardiovascular care. Task Force 6: Proposed access to care programs in the United States. PMID- 1593044 TI - Novel approach to the analysis of restenosis after the use of three new coronary devices. AB - Restenosis after coronary intervention has remained a vexing problem despite the introduction of nearly 24 newer coronary interventional devices. To more clearly evaluate the potential impact of three such new devices on restenosis, coronary lumen diameters were measured before, immediately after and at 6 months after intervention, and restenosis was analyzed using continuous geometric techniques. Lumen diameters were measured before and immediately after intervention in 223 coronary vessels treated with one of three new devices: a single Palmaz-Schatz stent (n = 87), directional atherectomy (n = 125) and laser balloon angioplasty (n = 11); 184 (83%) of the patients underwent follow-up angiography 6 months after treatment. The immediate increase in lumen diameter produced by the intervention (acute gain) and the subsequent reduction in lumen diameter between the time of intervention to 6 month follow-up study (late loss) were examined. For each of the three interventions, the restenosis rate at follow-up study was analyzed using a traditional dichotomous definition (greater than or equal to 50% diameter stenosis), as well as a novel graphic technique. Although the apparent restenosis rates differed significantly among the three interventions (19% for stents, 31% for atherectomy and 50% for laser balloon angioplasty; p = 0.02), late loss among the three interventions was equivalent (average 1 mm; p = 0.91). There were, however, marked differences in the acute gain achieved by the three interventions: 2.6 mm for stents, 2.2 mm for atherectomy and 2 mm for laser balloon angioplasty; p less than 0.001). It was these differences in acute gain rather than late loss that explained the observed differences in restenosis rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593045 TI - Regurgitant flow in cardiac valve prostheses: diagnostic value of gradient echo nuclear magnetic resonance imaging in reference to transesophageal two dimensional color Doppler echocardiography. AB - Gradient echo nuclear magnetic resonance (NMR) imaging and transesophageal two dimensional color Doppler echocardiography are flow-sensitive techniques that have been used in the diagnosis and grading of valvular regurgitation. To define the diagnostic value of gradient echo NMR imaging in the detection of regurgitant flow in cardiac valve prostheses and the differentiation of physiologic leakage flow from pathologic transvalvular or paravalvular leakage flow, 47 patients with 55 valve prostheses were examined. Color Doppler transesophageal echocardiography was used for comparison. Surgical confirmation of findings was obtained in 11 patients with 13 valve prostheses. Gradient echo NMR imaging showed regurgitant flow in 37 of 43 valves with a jet seen on transesophageal echocardiography and it detected physiologic leakage flow in 4 additional valves. There was 96% agreement between the two methods in distinguishing between physiologic and pathologic leakage flow. The methods differed on jet origin of pathologic leakage flow in six prostheses. The degree of regurgitation was graded by both NMR imaging and transesophageal echocardiography, according to the area of the regurgitant jet visualized; gradings were identical for 75% of valve prostheses. Quantification of jet length and area showed a good correlation between the two methods (r = 0.85 and r = 0.91, respectively). Gradient echo NMR imaging is a useful noninvasive technique for the detection, localization and estimation of regurgitant flow in cardiac valve prostheses. However, because transesophageal echocardiography is less time-consuming and less expensive, gradient echo NMR imaging is unlikely to displace transesophageal echocardiography and should be used only in the occasional patient who cannot be adequately imaged by echocardiography. PMID- 1593046 TI - Direct quantitation of right and left ventricular volumes with nuclear magnetic resonance imaging in patients with primary pulmonary hypertension. AB - To test the utility of electrocardiographically gated spin echo nuclear magnetic resonance (NMR) imaging in quantitating right and left ventricular volumes and function in patients with primary pulmonary hypertension, right and left ventricular end-diastolic and end-systolic volumes, stroke volumes and ejection fractions were determined in 11 patients with primary pulmonary hypertension and in 10 subjects with normal echocardiographic findings. Ventricular chamber volumes were computed by summing the ventricular chamber volumes of each NMR slice at end-diastole and end-systole. This technique was verified by comparison of results obtained by this method and with the water displacement volumes of eight water-filled latex balloons and ventricular casts of eight excised bovine hearts. In the patients with primary pulmonary hypertension, right ventricular volume indexes were 121 +/- 45 ml/m2 at end-diastole and 70.1 +/- 41.6 ml/m2 at end-systole; both values were significantly greater than values in the normal subjects (67.9 +/- 13.4 and 27.9 +/- 7.5 ml/m2, respectively). Left ventricular end-diastolic volume index was significantly less in the patients (44.9 +/- 9.7 ml/m2) than in the normal subjects (68.9 +/- 13.1 ml/m2). There was no significant difference in left ventricular end-systolic volume between the two groups (24.4 +/- 8.6 and 27.1 +/- 7.8 ml/m2, respectively). Right and left ventricular ejection fractions in the patients with primary pulmonary hypertension (0.43 +/- 0.21 and 0.46 +/- 0.15, respectively) were significantly less than values in normal subjects (0.59 +/- 0.09 and 0.6 +/- 0.11, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593047 TI - Quantitation of mitral regurgitation by transesophageal echocardiography with Doppler color flow mapping: correlation with cardiac catheterization. AB - Eighty consecutive patients who underwent both left ventriculography and single plane transesophageal echocardiography with Doppler color flow mapping were studied to compare the two techniques in the assessment of mitral regurgitation. Only the mosaic aspect of the regurgitant jet was included in the measurements. Values for inter- and intraobserver variability for the maximal regurgitant area measurements were 10 +/- 9% and 9 +/- 8%, respectively. The best correlation between angiography and Doppler color flow imaging was obtained with the maximal regurgitant area (r = 0.90). A maximal regurgitant area less than 3 cm2 predicted mild mitral regurgitation with a sensitivity of 96%, specificity of 100% and a predictive accuracy of 98%, whereas a maximal regurgitant area greater than 6 cm2 predicted severe mitral regurgitation with a sensitivity of 91%, a specificity of 100% and a predictive accuracy of 98%. A strong, although inferior, correlation was found for the maximal regurgitant area/left atrial area ratio (r = 0.81). A ratio less than 20% predicted mild mitral regurgitation with 94% accuracy, whereas a ratio greater than 35% predicted severe mitral regurgitation with 85% accuracy. Thus, single-plane transesophageal echocardiography with Doppler color flow mapping is an exquisitely sensitive technique for the diagnosis of mitral regurgitation. Minimal degrees of mitral regurgitation can be detected in approximately 62% of patients in whom no mitral regurgitation is detected by angiography. The mosaic maximal regurgitant area is a simple and easily obtainable Doppler echocardiographic index that provides an accurate estimation of mitral regurgitation severity. PMID- 1593048 TI - Comparison of preload recruitable stroke work, end-systolic pressure-volume and dP/dtmax-end-diastolic volume relations as indexes of left ventricular contractile performance in patients undergoing routine cardiac catheterization. AB - The end-systolic pressure-volume relation, the relation between stroke work and end-diastolic volume, termed the preload recruitable stroke work relation, and the relation between the peak of the first derivative of left ventricular pressure (dP/dtmax) and end-diastolic volume have been employed as linear indexes of left ventricular contractile performance in laboratory animals. The purpose of this study was to examine the relative utility of these indexes during routine cardiac catheterization in seven human subjects (mean age 48 +/- 18 [SD] years) with a normal left ventriculogram and coronary angiogram. Left ventricular pressure was recorded continuously with a micromanometer catheter, and left ventricular volume was derived from digital subtraction contrast ventriculograms obtained at 30-ms intervals. Transient occlusion of the inferior vena cava with a balloon-tipped catheter was employed to obtain beat to beat reductions in left ventricular pressure and volume over 8.7 +/- 1.7 cardiac cycles. Stroke work declined by 49 +/- 13% during vena caval occlusion, but end-systolic pressure fell by only 26 +/- 11%, and changes in dP/dtmax were small and inconsistent (12 +/- 22%). Consequently, the range of data available for determination of the preload recruitable stroke work relation greatly exceeded that for the end systolic pressure-volume relation and the dP/dtmax-end-diastolic volume relation, and much less linear extrapolation from the measured data was required to determine the volume-axis intercept. Preload recruitable stroke work relations were highly linear (r = 0.95 +/- 0.07), and much more so than end-systolic pressure-volume relations (r = 0.79 +/- 0.23).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593049 TI - Increased dispersion of "refractoriness" in patients with idiopathic paroxysmal atrial fibrillation. AB - The average interval between local depolarizations during atrial fibrillation, the so-called atrial fibrillation interval, was used as an index for local "refractoriness." This was based on the assumption that during fibrillation, cells are reexcited as soon as their refractory period ends. A very good correlation was found between refractory periods determined with the extrastimulus technique at a basic cycle length of 400 ms and atrial fibrillation intervals measured at the same epicardial sites of the right atrium. This new technique was used to assess dispersion in atrial fibrillation intervals in 10 patients with idiopathic paroxysmal atrial fibrillation and in a control group of 6 patients who were undergoing cardiac surgery. After a routine median sternotomy a multiterminal grid with up to 40 electrodes was placed over the right atrium, and atrial fibrillation was induced by premature stimulation. The average fibrillation interval in the test group, recorded at 247 sites, was 152 +/- 3 ms and that in the control group, recorded at 118 sites, was 176 +/- 8.1 ms (p less than 0.05). Dispersion in atrial fibrillation intervals, defined as the variance of the fibrillation intervals at all the recording sites, was three times larger in the group with paroxysmal atrial fibrillation than in the control group. This study suggests that both a shorter refractory period and a larger dispersion in refractoriness are responsible for the recurrence of atrial fibrillation. PMID- 1593050 TI - DDD pacing mode survival in patients with a dual-chamber pacemaker. AB - Dual-chamber (DDD) pacing mode survival was assessed by reviewing 486 consecutive initial transvenous DDD pacemaker implantations between December 1981 and December 1988 inclusive, with a mean follow-up time of 33 months. The patients' mean age was 71.4 years and 55% were male; 38% had dominant sinoatrial and 62% had dominant atrioventricular (AV) node disease. Nineteen patients (4%) underwent secondary operative intervention for lead dislodgement (n = 11), lead or pulse generator malfunction (n = 6) or infection (n = 2). During follow-up, 87 patients (18%) had their device permanently reprogrammed out of the DDD mode and 10 others (2%) required temporary reprogramming out of this mode; 12 patients who required device reprogramming were managed in other dual-chamber or atrial pacing modes. Reasons for reprogramming included atrial fibrillation (n = 48; 10%); loss of atrial sensing (n = 26; 5%); recurrent "endless loop" tachycardia (n = 5; 1%); lead dislodgement without repositioning (n = 4; 1%); pulse generator malfunction (n = 1; 1%) and other (n = 5; 1%). The occurrence of atrial fibrillation was associated with dominant sinoatrial disease and a prior history of atrial fibrillation; 19% of atrial sensing loss was attributable to early or faulty pacemaker technology. The DDD mode survival rate at 1, 2, 3, 4 and 5 years was, respectively, 90%, 88%, 84%, 79% and 78%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593051 TI - Deleterious effects of long-term single-chamber ventricular pacing in patients with sick sinus syndrome: the hidden benefits of dual-chamber pacing. AB - Nine hundred fifty patients who received three modes of primary pacemaker systems (581 dual-chamber universal [DDD], 84 atrioventricular-sequential ventricular inhibited [DVI] and 285 ventricular-inhibited [VVI]) over 12 years were studied retrospectively to determine the effect of pacing mode on patient longevity and the subsequent development of chronic atrial fibrillation or flutter. All patients were followed up continuously for 7 to 8 years. Patients were classified according to indication for permanent pacing (sick sinus syndrome or other indication), age at pacemaker implantation (less than or equal to 70 or greater than 70 years) and history of atrial tachyarrhythmia. Fourteen percent of patients developed atrial fibrillation at some time during the study period. Of those, 4% had a DDD pacemaker, 8% had a DVI pacemaker and 19% had a VVI pacemaker. At 7 years, atrial fibrillation was significantly more frequent in the VVI group than in the DDD and DVI groups. In patients with sick sinus syndrome, the incidence rate was even higher in the VVI group but approximately the same in the DDD and DVI groups. Patients in the VVI and DVI groups who had had previous atrial tachyarrhythmia had a significantly higher incidence of atrial fibrillation at 7 years than did those in the DDD group. During the entire period there were 130 deaths in the study group, including 22% of patients with a DDD pacemaker, 38% of those with a DVI pacemaker and 50% of those with a VVI pacemaker. Patient survival at 7 years was lower in the VVI group than in the DDD or DVI groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593052 TI - Mitral atresia with a large left ventricle and an underdeveloped or absent right ventricular sinus: clinical profile, anatomic data and surgical considerations. AB - In mitral atresia with a large left ventricle, the tricuspid valve is either straddling and biventricular or entirely left ventricular. To learn how to assess the identity of the tricuspid valve in such cases 15 heart specimens were examined as well as the echocardiograms of 10 living patients. When the right ventricular sinus was underdeveloped (11 cases), a straddling tricuspid valve was present; when it was absent (14 cases), the tricuspid valve was entirely left ventricular. Regardless of biventricular or exclusively left ventricular attachments, the tricuspid valve was tricommissural (at postmortem examination or on echocardiography) in 22 cases (88%). Its chordal attachments showed considerable variations but were usually paraseptal or on the ventricular septal crest or conal septum. When biventricular, the tricuspid valve straddled through an inlet ventricular septal defect. Clinical or anatomic evidence, or both, of tricuspid regurgitation was present in 14 cases (56%). It is concluded that 1) the identity of the atrioventricular valves is reflected in their chordal attachments more accurately than in their leaflet morphology and depends primarily on the type of ventricular loop present; 2) as a rule, the tricuspid valve is right-sided in D-looped and left-sided in L-looped ventricles; 3) valve identity expressed as the number and position of the papillary muscle attachments is generally recognizable echocardiographically and can be used to diagnose the type of ventricular loop that is present; and 4) the presence and degree of tricuspid regurgitation deserve attention when choosing optimal palliative surgery. PMID- 1593053 TI - Diagnosis of total anomalous pulmonary venous drainage by Doppler color flow imaging. AB - Over a 2.5-year period, 16 consecutive infants were prospectively diagnosed as having total anomalous pulmonary venous drainage. The sites of drainage were cardiac (to the coronary sinus) in four patients, supracardiac in nine, infracardiac in two and mixed in one patient. In every case, two-dimensional echocardiography with color flow imaging enabled complete and correct diagnosis of the sites of drainage and the presence or absence of pulmonary venous obstruction. The echocardiographic findings were verified at surgery or autopsy in all. Color flow imaging rapidly provided information about the direction and mean velocity of flow through abnormal vascular structures in any two-dimensional echocardiographic plane. It facilitated the acquisition of quantitative velocity information with standard Doppler ultrasound techniques by identifying areas of high velocity or turbulent flow and was invaluable in the assessment of anomalous pulmonary venous drainage occurring either as an isolated anomaly or in conjunction with complex intracardiac lesions. PMID- 1593054 TI - Comparison of the cost of radiofrequency catheter modification of the atrioventricular node and medical therapy for drug-refractory atrioventricular node reentrant tachycardia. AB - The purpose of this study was to determine the charges for radiofrequency catheter modification of the atrioventricular (AV) node in 15 patients with symptomatic AV node reentrant tachycardia despite pharmacologic therapy and to compare these charges with the estimated charges for health care utilization by the same patients before the catheter procedure was performed. There were seven men and eight women with a mean age of 50 +/- 17 years. The mean duration and frequency of symptoms were 16 +/- 9 years and 4.5 +/- 6 episodes/month, respectively. Fourteen of the 15 patients required only one procedure for diagnosis and cure of AV node reentrant tachycardia and 1 patient required two sessions. All patients underwent electrophysiologic study before discharge from the hospital to confirm the short-term efficacy of the procedure. The mean duration of the hospital stay was 3 +/- 1.5 days and the mean total charge/patient expressed in 1991 dollars was $15,893 +/- $3,338 for catheter modification. These total charges consisted of hospital charges of $8,105 +/- $2,466 and physician charges of $7,788 +/- $971. All patients had a successful outcome and required no additional antiarrhythmic therapy. The estimated cost of health care utilization for these 15 patients before cure of AV node reentrant tachycardia was $7,651/patient per year. These estimated costs included charges incurred for emergency room visits, office visits, hospitalizations and antiarrhythmic drug therapy. In conclusion, the results of this study indicate that the annual health care costs incurred by patients who have symptomatic, drug refractory paroxysmal supraventricular tachycardia caused by AV node reentry are substantial.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593055 TI - Recurrence of conduction in accessory atrioventricular connections after initially successful radiofrequency catheter ablation. AB - The purpose of this study was to characterize the incidence and clinical features of accessory pathway recurrence after initially successful radiofrequency catheter ablation and to identify variables correlated with recurrence. Radiofrequency ablation was performed with a 7F deflectable tip catheter with a large (4 mm in length) distal electrode. Left-sided accessory pathways were approached through the left ventricle and right-sided pathways by way of the right atrium. Patients were included in the study if 1) they had an initially successful procedure, defined as the absence of accessory pathway conduction immediately after ablation, and 2) had undergone a 3-month follow-up electrophysiologic test or had documented recurrence of accessory pathway conduction. Accessory pathway conduction recurred after initially successful ablation in 16 (12%) of 130 patients. Almost half (7 of 16) of these recurrences were in the 1st 12 h after ablation, and the last occurred after 106 days. Return of delta waves on the electrocardiogram (ECG) or spontaneous paroxysmal supraventricular tachycardia was the initial indication of recurrence in 15 of the 16 patients. Two patients with manifest accessory pathways exhibited recurrence with exclusively concealed accessory pathway conduction. Accessory pathways ablated from the tricuspid anulus (right free wall or septal accessory pathways) had a much higher recurrence rate (24%) than did those on the mitral anulus (6%). Fourteen of 15 patients have had successful repeat accessory pathway ablation after the initial recurrence. After a mean follow-up period of 4 +/- 3 months, there have been no repeat recurrences of any of these accessory pathways. It is concluded that accessory pathway recurrence is infrequent after successful radiofrequency catheter ablation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593056 TI - Long-term clinical and angiographic follow-up of patients treated with the self expanding coronary stent for acute occlusion during balloon angioplasty of the right coronary artery. AB - A self-expanding coronary stent was implanted in 17 patients to treat acute occlusion of the right coronary artery after percutaneous transluminal angioplasty. There were 2 women and 15 men, with a mean age of 59 +/- 8 years. All patients underwent at least one follow-up angiographic examination 4 to 6 months after implantation and six patients had additional follow-up angiography. During a mean follow-up interval of 32 +/- 10 months no patient died or had a myocardial infarction. Restenosis within the stent did not occur. Two patients had a new stenosis adjacent to the stent. Stent occlusion was found on follow-up angiography in one patient who had not been treated with an antiplatelet agent. The mean intraluminal diameter was 2.77 +/- 0.5 mm after implantation and 2.67 +/ 0.5 mm on follow-up angiography. It is concluded that coronary stenting is effective in treating right coronary artery occlusion after balloon angioplasty. Immediate and long-term outcome suggest that the right coronary artery may be a particularly favorable site for stent implantation. PMID- 1593057 TI - Ineffectiveness of colchicine for the prevention of restenosis after coronary angioplasty. AB - Colchicine, an antimitogenic agent, has shown promise in preventing restenosis after coronary angioplasty in experimental animal models. A prospective trial was conducted involving 197 patients randomized in a 2:1 fashion to treatment with oral colchicine, 0.6 mg twice daily (130 patients), or placebo (67 patients) for 6 months after elective coronary angioplasty. Treatment in all patients began between 12 h before angioplasty and 24 h after angioplasty. Compliance monitoring revealed that 96% of all prescribed pills were ingested. Demographic characteristics were similar in colchicine- and placebo-treated groups. A mean of 2.7 lesions/patient were dilated. Side effects resulted in a 6.9% dropout rate in the colchicine-treated patients. Complete quantitative angiographic follow-up was obtained in 145 patients (74%) with 393 dilated lesions. Quantitative angiographic measurements were obtained in two orthogonal views at baseline before angioplasty and immediately and at 6 months after angioplasty. The quantitative mean lumen diameter stenosis before angioplasty was 67% both in the 152 lesions in the placebo-treated group and in the 241 lesions in the colchicine treated group; this value was reduced to 24% immediately after angioplasty in the lesions in both treatment groups. At the 6-month angiogram, lesions had restenosed to 47% lumen diameter narrowing in the placebo-treated group compared with 46% in the colchicine-treated group (p = NS). Forty-one percent of colchicine-treated patients developed restenosis in at least one lesion compared with 45% of the placebo-treated group (p = NS). In conclusion, colchicine was ineffective for preventing restenosis after coronary angioplasty. PMID- 1593058 TI - Origin of arterial wall dissections induced by pulsed excimer and mid-infrared laser ablation in the pig. AB - To study adjacent tissue damage after delivery of holmium, thulium and excimer laser pulses, porcine thoracic aortas were irradiated in vivo. After 3 days, microscopic analysis of 67 craters produced by all three lasers demonstrated large dissections extending from the craters. The mean diameter of the dissections was smaller for excimer-induced craters (1.38 +/- 0.42 mm; n = 22) than for holmium-induced (2.7 +/- 0.87 mm; n = 22) and thulium-induced (2.37 +/- 0.42 mm; n = 14) craters (p less than 0.01 vs. mid-infrared dissections). In addition, microscopic analysis demonstrated necrosis adjacent to the crater. The lateral necrotic zones of the thulium-induced craters were smaller than the holmium- and excimer-induced necrotic zones (p less than 0.01). To identify the origin of the excessive tissue tearing, laser-saline and laser-tissue interaction were compared in vitro by time-resolved flash photography. In saline solution, the mid-infrared lasers showed bubble formation on a microsecond time scale. The excimer laser produced similar bubbles in the vicinity of tissue. For all three lasers, elevation of the tissue surface was shown during in vitro ablation. Dimension (diameter up to 4 mm) and time course (rise time of 100 to 300 microseconds) of bubble formation and tissue elevation were strikingly similar. Thus, tissue dissections are caused by the expansion of a vapor bubble within the target tissue. Coronary dissections after excimer and mid-infrared laser angioplasty might be related to the forceful bubble expansion. PMID- 1593059 TI - Laser-induced dissections: pathogenesis and implications for therapy. PMID- 1593060 TI - Russek Lecture. Must cardiology lose its heart? AB - Regulations and restrictions imposed by external agencies are forcing cardiologists into an unnatural self-protective and defensive posture against their patients. The key to breaking the pattern of mutual skepticism and mistrust lies in returning the focus to its rightful place: the patients' needs. Thus, payment systems must be devised that reward cognitive skills, time spent with patients and continuity of care as they reward technologic interventions and procedures. In advocating necessary changes in the system, only physicians themselves can provide a convincing voice in the political arena. They must look beyond their own self-interest to recapture the moral and ethical high ground where the best care of their patients and their own professional satisfaction stand side by side. PMID- 1593061 TI - Lesion morphology and coronary angioplasty: current experience and analysis. AB - From July 1, 1990 to February 28, 1991, 533 consecutive patients with 764 target vessels and 1,000 lesions underwent coronary angioplasty. Procedural success was achieved in 92.3%, untoward (major cardiac) events occurred in 3% (0.8% myocardial infarction, 1.3% emergency coronary bypass grafting and 0.9% both; there were no deaths). An unsuccessful uncomplicated outcome occurred in 4.7%. Lesion analysis using a modified American College of Cardiology/American Heart Association classification system showed that 8% were type A, 47.5% were type B and 44.5% were type C (36% of type B and 11% of type C were occlusions). Angioplasty success was achieved in 99% of type A, 92% of type B and 90% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.01). Untoward events occurred in 1.2% of type A, 1.9% of type B and 2% of type C lesions (p = NS). An unsuccessful uncomplicated outcome occurred in 0% of type A, 6% of type B and 7% of type C lesions (A vs. B, p less than 0.05; B vs. C, p = NS; A vs. C, p less than 0.05). Among the unsuccessful uncomplicated outcome group, occlusion occurred in 49%: 38% of type B and 59% of type C lesions. With B1 and B2 subtypes, success was obtained in 95% and 89.5% and untoward events occurred in 1.5% and 2.3% and an unsuccessful uncomplicated outcome in 3.7% and 8%, respectively. C1 and C2 subtyping showed success in 91% and 86%, untoward events in 1.3% and 6% and an unsuccessful uncomplicated outcome in 7.5% and 8.5%, respectively. Among the 764 vessels, success was obtained in 89.5% and untoward events occurred in 2.5% and an unsuccessful uncomplicated outcome in 8%. Assessment of lesion-vessel combinations showed a less favorable outcome with type C lesions and combinations of A-B, B-C and multiple (more than three lesions) type B and C vessels. Statistical analysis of morphologic factors associated with angioplasty success included absence of (old) occlusion (p less than 0.0001) and unprotected bifurcation lesion (p less than 0.001), decreasing lesion length (p less than 0.003) and no thrombus (p less than 0.03). The only significant factor associated with untoward events was the presence of thrombus (p less than 0.003). Predictors of an unsuccessful uncomplicated outcome included old occlusion (p less than 0.0001) and increasing lesion length (greater than 20 mm) (p less than 0.001), unprotected bifurcation lesion (p less than 0.05) and thrombus (p less than 0.03). PMID- 1593062 TI - Plaque disruption and the acute coronary syndromes of unstable angina and myocardial infarction: if the substrate is similar, why is the clinical presentation different? AB - In a majority of instances, both unstable angina and acute myocardial infarction occur secondary to plaque disruption and thrombus formation. Although the pathogenetic substrates are similar the clinical presentations are quite different. It is hypothesized in this editorial review that the amount of acute thrombus formation and specifically fibrin deposition is greater in myocardial infarction than in unstable angina. Both angiographic studies and studies analyzing the response to thrombolytic agents suggest more thrombus in myocardial infarction than in unstable angina. These data have recently been substantiated by angioscopic observations in these acute syndromes suggesting that more platelet-rich (whitish) thrombus occurs in unstable angina and more red thrombus in myocardial infarction. The red thrombus presumably would be more responsive to thrombolytic agents. Furthermore, it is proposed that these differences between syndromes in acute thrombus formation can be explained by the interplay of vessel wall injury, coagulation variables or stasis of blood flow occurring at or after the time of presentation. Therefore, acute myocardial infarction is associated with occlusive, fibrin-rich thrombus, whereas in unstable angina, the thrombus is nonocclusive, mural and possibly more platelet-rich. However, the clinical syndrome that ultimately develops after plaque disruption is dependent not only on the amount of acute thrombus formation but on the net result of all factors that influence the balance between coronary blood supply and myocardial oxygen demand. PMID- 1593063 TI - Unstable angina: outcome according to clinical presentation. AB - Unstable angina is a broad clinical diagnosis that includes patients at different levels of risk for an unfavorable outcome. Although, as in other categories of coronary artery disease, the state of left ventricular function and the extent of coronary artery disease will determine long-term prognosis, recognition of clinical markers of an early unfavorable course may be of value in defining management strategies. This review focuses on the relevance of baseline clinical characteristics and noninvasive data in assessing the prognostic significance of unstable angina in light of its presenting features. Recurrence of chest pain within 48 h after admission carries a reduction in likelihood of survival of about 20% in patients with progressive or prolonged angina. Similarly, ECG changes on admission have a negative prognostic implication, particularly in rest angina, as they predict recurrence of ischemia, myocardial infarction or need for revascularization in 80% of the patients. In variant angina, determinants of prognosis are level of disease activity, as judged by recurrence of pain, ECG changes and use of calcium channel antagonists. Patients with angina after a myocardial infarction who have more than one episode of either angina or silent ischemia in 24 h have a 10% reduction in probability of survival during the 1st year compared with that of asymptomatic patients. An abrupt course, or the rapidity with which symptoms develop, is the main determinant of prognosis in new onset angina. Thus, recurrent angina and ECG changes appear to be relevant prognostic markers in the patient subsets considered; if these are present, early coronary angiography must be performed and revascularization procedures should be considered without delay. PMID- 1593064 TI - Obstruction of right ventricular outflow tract caused by intracavitary metastatic disease: analysis of 14 cases. AB - Obstruction of the right ventricular outflow tract from metastatic disease is rare. Eleven previous case reports and three new cases are presented. Two tumor types (pancreas and breast), not previously associated with right ventricular outflow tract obstruction, are included. Congestive symptoms, systolic murmur and right axis deviation or right bundle branch conduction abnormality were universal features. Echocardiography is valuable in the delineation of metastatic cardiac involvement and the detection of intracardiac gradients. Adverse hemodynamic consequences developed in 3 of 10 patients who underwent right heart catheterization in which two died. This procedure should be performed only when absolutely necessary. Metastatic obstruction of the right ventricular outflow tract should be considered in the absence of widespread malignancy because the heart was the sole site of metastasis in 5 of 10 autopsy patients. Two patients with solitary cardiac metastasis benefited from resection of the obstructing tumor, underscoring the importance of early identification of this subgroup. PMID- 1593065 TI - Electrocardiographic criteria for identifying false positive exercise tests. PMID- 1593066 TI - Floppy eyelid syndrome: a case report and clinical review. AB - Floppy eyelid syndrome is a clinical entity associated with a chronic papillary conjunctivitis which is resistant to topical therapeutic agents. The disorder is usually found in older, obese males with upper eyelids which are loose, rubbery, and easily everted. This paper is a review of the clinical characteristics and treatment of the syndrome and includes a case of a 16-year-old male with floppy eyelid syndrome, one of the youngest reported. PMID- 1593067 TI - Floppy eyelid syndrome associated with keratoconus. AB - Keratoconus has been associated with various ocular and systemic disorders. It has been linked, in a few cases, with floppy eyelid syndrome (a disorder characterized by a soft rubbery upper tarsus, papillary conjunctivitis and obesity). A 40-year-old male presented with a complaint of gradually decreasing vision in the right eye. An intermittent right exotropia had become constant and he was unable to maintain fixation voluntarily. Corneal findings were consistent with keratoconus. Floppy eyelid syndrome was also diagnosed. An underlying connective tissue disorder may link these two disorders. PMID- 1593068 TI - Contact lenses in the U.S. Army attack helicopter environment: an interim report. AB - Recent technological advances have had a major impact on military aviation. While modern methods of providing visual information via electro-optics/visionics systems have extended the aviator's operational envelope, these devices are becoming increasingly incompatible with spectacle wear. Since close to 22 percent of Army aviators are ametropic (spectacle wearing), alternative means of providing a refractive error correction need to be investigated. One alternative being considered is the use of a contact lens correction. Since November 1988, the U.S. Army Aeromedical Research Laboratory (USAARL) has been conducting two AH 64 "Apache" contact lens research projects in order to develop a comprehensive database on contact lens wear in a variety of environments. A three-tier contact lens fitting system is being used: two different types of soft lenses and one rigid gas permeable (RGP) lens type. The wearing schedule is set at a maximum of 7 days/6 nights of extended lens wear. Fundamental operational data is being chronicled by unit flight surgeons. Standard clinical data is being used in ongoing command deliberations on future medical policy decisions concerning contact lens wear by Army aviators. Basic research information is being gathered in an effort to determine the fundamental physiological response of the cornea to the presence of a contact lens. Data through July 31, 1990 are presented. The subjective assessment of contact lens applications within the aviation community is universal acceptance. While current clinical data indicate some ocular health risk, flight safety risks are minimal. Establishment of long-term contact lens efficacy will likely depend on the ensuing analysis of physiological data. PMID- 1593069 TI - Variations in physician response to consultation requests for Hollenhorst plaques: a pilot study. AB - This is a report on physicians' response to a pilot survey regarding the method of management of a patient sent to them for a health evaluation because of a Hollenhorst plaque detected during a routine eye examination. Several specialties and sub-specialties were surveyed. The results demonstrate a wide variability in the methods chosen for management of the patient, indicating the need to consider standardizing the health evaluation. A review of literature suggests that the patient with a Hollenhorst plaque is at increased risk for both cardiovascular and cerebrovascular disease and appropriate measures should be taken to minimize the risk. The pilot survey suggests that more in-depth surveys are necessary to establish standards of care for the patient with Hollenhorst plaques as well as other ocular conditions related to systemic disorders. PMID- 1593070 TI - Cleaning and storage of rigid contact lenses prior to dispensing. AB - Most care regimens used with rigid contact lenses are composed of three solutions: 1) a "cleaning" solution; 2) a "combination" solution intended for storage, disinfection, and wetting prior to placement of rigid lenses on the eye; and 3) an in-eye "rewetting" or "lubricating" solution. While solutions (1) and (3) have only single functions, solution (2) must fulfill three fairly disparate functions. A "2-solution" care regimen is offered by Sherman Pharmaceuticals and consists of (a) a solution for cleaning, storage, and disinfection; and (b) a "wetting" solution that doubles as an in-eye lubricant. Through a more compatible and efficient matching of multiple functions within solutions, Sherman Pharmaceuticals claims to more adequately clean and prepare rigid gas-permeable (RGP) lens surfaces for wear. We investigated this strategy in terms of in-eye wettability of initially "ill-prepared" RGP lens surfaces, as measured with the in vivo contact angle technique. For this study, lenses were intentionally not cleaned of residues or solvents by the manufacturer at the end of production so as to create the well-known "first-day non-wetting syndrome." The ability of the 2-solution care regimen to even then provide wettable surfaces was compared to that of a saline control "regimen" and the most popular competing "3-solution" care system. We concluded that use of both care regimens dramatically enhanced in eye wettability and, therefore, reduced the incidence of the "first-day non wetting syndrome". However, the 2-solution care regimen provided significantly better wettability overall, lower incidence of functionally non-wetting surfaces, and more consistently wettable RGP lenses. PMID- 1593071 TI - Clinical performance of two opaque, tinted soft contact lenses. AB - Comfort, visual acuity, visual fields, daytime corneal edema and corneal staining were evaluated on 22 subjects wearing opaque tinted and non-opaque control hydrogel lenses. CooperVision Permaflex Mystique (38% polymacon) and Wesley Jessen Durasoft 3 Colors (55% phemfilcon A) opaque lenses were compared to non opaque lenses from the same manufacturers (CooperVision CV Classic and Wesley Jessen Durasoft 3). Subjects were randomly assigned one type of opaque lens and one clear lens on each of two days, and two opaque lenses on another day. All lenses yielded similar results in terms of comfort, visual acuity, visual fields and corneal staining. The only visual problem with the opaque lenses was the reporting of "haziness" (usually peripheral) in 72 percent of Mystique and 59 percent of Durasoft 3 Colors trials. The greatest daytime corneal edema, 4.7 percent, occurred with the Mystique lens compared with 2.7 percent with CV Classic and 1.8 percent and 1.7 percent with the opaque and clear Durasoft 3 lenses respectively. These levels of edema were associated with a 40 percent incidence of striae with Mystique (17/43), 14 percent with the CV Classic (3/21 eyes), 5 percent with Durasoft 3 clear (1/22 eyes) and 2 percent with Durasoft 3 opaque lenses (1/44 eyes). Corneal swelling correlated with the measured Dk/L of the lenses. The Durasoft 3 Colors lens was the opaque tinted lens of choice based primarily on corneal physiology. PMID- 1593072 TI - The Ishihara Test: on the prevention of job discrimination. AB - Experiments were carried out to answer questions relative to the use of the 24 plate edition of the Ishihara Test for Colour-Blindness as a screening instrument for detecting the presence of inherited color defective vision. Subjects and their numbers varied between some experiments. Some subjects had normal color vision and others had inherited color defectiveness as confirmed with a Nagel anomaloscope. Most of the 157 subjects who participated in the experiments were either young deaf college students or police recruits with normal hearing who did not pass the Ishihara Test during their respective visual screening processes. Some hearing faculty and staff participated as part of Experiment 2. Item analysis and statistics applied to test the significance of differences between group means were applied to derive the following results: (a) test-retest reliability for the Ishihara is high both for persons with inherited color defectiveness and normal color vision; (b) persons making fewer than five errors on the first 13 plates made common incidental (nontypical) errors not related to color defective vision; and (c) five (5) or more errors was identified with some degree of inherited color defective vision, and subsequent referral for additional color vision diagnostics is warranted. Failure to utilize the recommended "pass-fail" criterion and/or to allow clients who fail color vision screening recourse to additional testing to establish type and degree of color defective vision may unnecessarily lead to job discrimination and/or interfere in a negative manner with the career selection process. PMID- 1593073 TI - Stroke. AB - Stroke is a primary cause of death and debilitation in the United States. There is both a geographical and race distribution throughout the country. A major health initiative over the next few years is to further reduce the incidence of stroke, especially in the STROKE BELT. There are several "eye signs" of impending stroke including transient monocular blindness, retinal vascular occlusive diseases, ischemic retinal syndromes, visual field defects and retinal emboli. Optometrists can serve as a first line of defense in the death and debilitation from stroke by the recognition of the "eye signs" associated with the most common variant of stroke--the thromboembolism. The primary care provider must also provide recommendations regarding the proper consultation to avert a total stroke. PMID- 1593074 TI - Memory as resistance, and the telling of a dream. AB - Traditional analytic orientation to memory as subject to repression has overshadowed examination of some of the ego's other activities bearing on memory. The author examines the defensive use of memory with the analytic goal of maximum autonomous access for the patient to the ego's previously unconscious management of intrapsychic conflict. A close scrutiny of an example of this in the form of the telling of a dream explores this resistance process and illustrates a technical approach. Some aspects of this perspective are considered in relation to traditional approaches to dream material. Certain technical priorities for differing clinical settings are discussed. PMID- 1593075 TI - Therapeutic technique in psychoanalysis and psychoanalytic psychotherapy. AB - As the distinctions between what we consider to be psychoanalysis and what we consider to be psychoanalytic psychotherapy have become more uncertain and more blurred, it follows that it is equally difficult to designate the techniques that would be appropriate and specific for each modality. The problem has been compounded by the fact that in recent years psychoanalysis in the United States has become considerably less homogeneous than in the past and the ego psychological structural model is no longer the only point of view in the psychoanalytic marketplace. Further, with alterations in the criteria for analyzability, cases which, generally, had not been viewed as suitable for analysis, have been appearing with increasing frequency on psychoanalysts' couches. We have also recognized that the degree of congruence between our expectations from and the results of psychoanalytic treatment was often less than anticipated. It appears that analysts have become considerably less arbitrary about what psychoanalysis is and how a psychoanalysis can be carried out. The author is unable to delineate one technique that is intrinsic to and limited to psychoanalysis. There are, however, differences in degree and emphasis in the ways in which various techniques are applied in the therapy of psychoanalysis as compared to the therapy of psychoanalytic psychotherapy. Special attention is given to the role of a psychoanalytic process and the central place the analysis of resistance plays in psychoanalytic therapy. PMID- 1593076 TI - An investigation into some implications of a Vygotskian perspective on the origins of mind: psychoanalysis and Vygotskian psychology, Part I. AB - The Russian psychologist Lev Vygotsky proposed an analysis of language, thought, and internalization that has direct relevance to the current concerns of psychoanalysts. Striking methodological and conceptual similarities and useful complementarities with psychoanalysis are discovered when one peers beneath the surface of Vygotskian psychology. Our adaptation of Vygostsky's views expands upon Freud's assigned role to language in the topographic model. We suggest that the analysand's speech offers several windows into the history of the individual, through prosody, tropes, word meaning, and word sense. We particularly emphasize Vygotsky's views on the genesis and utilization of word meanings. The acquisition of word meanings will contain key elements of the internal climate present when the word meaning was forged. Bearing this in mind, crucial theoretical questions follow, such as how psychoanalysis is to understand the unconscious fantasies, identifications, anxieties, and defenses associated with the psychodynamics of language acquisition and later language usage. We propose that the clinical situation is an ideal place to test these hypotheses. PMID- 1593077 TI - From analytic surface to analytic space. AB - Utilizing a clinical illustration, the concept of the surface of the patient's mind, which arose early in analytic history, is reexamined in relation to the analytic space, the unique affective and communicative dyadic context of the analytic process. The shift from analytic surface to analytic space reflects in clinical theory the metapsychological shift from early structural views to current appreciation of compromise formation. Also, this approach permits broadening of consideration of active unconscious forces in both the patient and the analyst. PMID- 1593078 TI - On the clinical utility of the concept of depressive affect as signal affect. AB - The author reviews the scant literature relating to the concept of depressive affect as an affect parallel to anxiety. Then, through the presentation of detailed clinical psychoanalytic data, in particular the patient's associations to interpretation, he demonstrates the value to the conduct of a psychoanalysis of an awareness of the role of depressive affect as a signal affect that triggers defense. PMID- 1593079 TI - Psychoanalytic and biological approaches to mental illness: schizophrenia. AB - Biological psychiatrists tend to look upon the phenomena of mind and meaning, which are the data of psychoanalysis, as meaningless epiphenomena, and propose reductive explanations of complex mental states, whereas psychoanalysts tend to ignore the proliferation of neurobiological data indicating the importance of constitutional factors in mental illness. Interactive models which confuse biological causes and psychological consequences, or vice-versa, are theoretically unsound. A scientific model hierarchy is proposed, along with some principles for coexistence and collaboration between neurobiology and psychoanalysis. The problem is illustrated with schizophrenia, a condition whose probable biological underpinnings are now generally considered to remove it from the realm of psychoanalysis. Schizophrenia-vulnerable phenotypes consistent with organic findings and clinical observations are hypothesized, and some ideas about their development in the context of early object relations, leading to pathological forms of symbiosis, are elaborated. A neurobiological rationale for the psychoanalytic treatment of schizophrenia is presented, and special problems related to the biological and symbiotic substrate are examined. PMID- 1593080 TI - A variation on Freud's theme in "A child is being beaten"--mother's role: some implications for superego development in women. AB - Clinical material is presented leading to a discussion of beating fantasies which varies from Freud's model. Analysis shows that the fantasied role girls assign to mother as the punisher in the oedipal drama is equivalent to the fantasied role boys ascribe to father as castrator. For both sexes, castration anxiety spurs the internalization of parental prohibitions, the repression of oedipal wishes, and the subsequent structuralization of the superego. Mother establishes the "oedipal law" for the girl analogously to father's doing the same for the boy. The role that such fantasies play in the formation of the female superego is examined. PMID- 1593081 TI - The role of support in psychoanalysis. AB - A two-factor theory of clinical psychoanalysis is proposed. In accordance with the predominant position of the structural-adaptational ("classical") approach in psychoanalytic theory, the power of interpretation and insight in clinical psychoanalysis has received ample attention in psychoanalytic literature. There seems, however, to be a growing awareness among analysts that not all the facts of an analytic treatment can be accounted for by this approach alone. A second factor is increasingly recognized: the power of adequate support provided by the analyst and resulting in a specific experience by the analysand. In the application of the developmental ("postclassical") approach of psychoanalytic theory, the importance of this support-experience factor in the treatment of ordinary neurosis by means of ordinary psychoanalysis is emphasized. The relative neglect of this aspect of clinical psychoanalysis may be indicative of the present-day dilemma of how to translate advances in theoretical knowledge of mental development into the therapeutic praxis of psychoanalysis. There may, however, be another important reason. Support and experience are phenomena often occurring on the nonverbal level. In contrast to interpretation and insight, they are usually not voiced, let alone distinctly and loudly expressed. They are the silent power of psychoanalysis. PMID- 1593082 TI - Art alone endures. AB - Sigmund Freud, a passionate collector of antiquities, often treated these objects as animate beings. He described such blurring of boundaries between persons and things in the protagonist of W. Jensen's novella, Gradiva. Freud began collecting when his father died, but his unusual attitude toward artefacts was established much earlier, presumably as a consequence of repeated early disappointments in human caretakers. It is postulated that this adaptive maneuver was not simply a displacement of love and hate, but a turning away from vulnerability in relationships, toward attachments over which he might retain effective control. The Freud Collection is largely focused on Greco-Roman and Egyptian objects. Freud's profound interest in classical civilization was established in childhood; he was particularly concerned with the struggle between Aryan Rome and Semitic Carthage, a conflict in which he identified with both sides. This ambivalence reflected growing up within a marginal Jewish family in a Germanic environment. Commitment to classical ideals represented an optimal manner of bridging these contrasting worlds. Egyptian artefacts were, for Freud, links to the prehistory of the Jewish people; they also represent an era when maternal deities found their proper place in man's pantheon--an echo of Freud's prehistoric past. PMID- 1593083 TI - The concept of phylogenetic inheritance in Freud and Jung. AB - At the height of their collaboration in late 1911, Freud had succeeded in persuading Jung of the role of phylogenetic factors in the etiology of neuroses and psychoses. Phylogenetic considerations play an important part in the formulation of Jung's genetic standpoint of psychology with its conception of a desexualized primal libido, which figured prominently in the dispute which ended the relations between Freud and Jung. Freud's unpublished draft of "Overview of the Transference Neuroses" was in part an attempt to counter Jung's revisions of libido theory by using phylogenetic considerations to reaffirm his original conception of a unified sexual libido. Despite the sharp divergence of many aspects of their respective psychologies after the break, a conception of phylogenetic inheritance continued to play an important role in their developing theoretical formulations. PMID- 1593084 TI - A research-based reconsideration of the psychoanalytic theory of dreaming. AB - We present a brief review of sleep research which, when combined with psychoanalytic experience, has led to the hypothesis that REM sleep and dreaming serve the function of adaptation by the process of integration of information. We then report the results of a study of dreams, based on this hypothesis. We studied dreams and their relation to waking mental activity and found a correlation between problems in manifest dreams and those in pre- and postsleep waking life. Dreams can be understood on the basis of problems that appear in them. We also found evidence for a relation between the solution of problems in dreams and the fate of those problems the next day. We discuss these findings in relation to some of the controversies about dreaming, and then present suggestions for future research. PMID- 1593085 TI - When theory and practice diverge: gender-related patterns of referral to psychoanalysts. AB - This study tests the hypothesis that female analysts, relative to male analysts, receive a disproportionately small percentage of male referrals. Referral patterns for 170 analysts from four institutes accredited by the American Psychoanalytic Association were examined. One thousand, five hundred and ten patients referrals were studied. The findings were extremely robust and offered dramatic confirmation of our hypothesis. The major implications of the study are as follows: (1) Women analysts receive relatively few adult male referrals, making it difficult for them to gain requisite clinical experience with men. (2) Analysts and nonanalysts alike demonstrate a reluctance to refer male patients to female analysts. (3) Adult referrals, including those made by analysts, are significantly influenced by the issue of gender match between patient and analyst. (4) Analysts' behavior with regard to making referrals does not correspond to explicit clinical theory regarding how analysts make referrals- specifically, the extent to which gender influences the referral process is not adequately described by theory. We believe that these findings are of some concern from the standpoint of analytic education and that they also raise questions regarding unacknowledged aspects of how gender match between patient and analyst enters into clinical decision making.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593086 TI - Analysis of the transference neurosis in a child with transsexual symptoms. AB - This paper touches on two issues that have been disputed by child analysts: the genesis of the transsexual symptom complex, and the question of transference neurosis in child analysis. My observation, as reported previously (Loeb and Shane, 1980) and shown in the present case, is that the transsexual symptom complex can develop out of intrapsychic conflict and can be resolved in a fully developed transference neurosis. In the analysis of a four-and-a-half-year-old boy with transsexual symptoms, I was abstinent--not benevolent or supportive--and both positive and negative transference feelings developed into a full-blown transference neurosis. Then, as I interpreted its elements, we worked through his conflicts, which manifested themselves as acting out of his identification with his aggressive, seductive, and castrating grandmother. As he came to understand his conflicts, the boy's transsexual symptoms vanished. PMID- 1593087 TI - Research on the efficacy of psychoanalysis. PMID- 1593088 TI - Witnessing pornography and the reconstruction of suspected child sexual molestation. PMID- 1593089 TI - Differential control of sympathetic activity to kidney and skeletal muscle by ventral medullary neurons. AB - A rise in arterial blood pressure can be evoked by microinjections of D,L homocysteic acid into localized regions of the ventrolateral medulla of the cat. Three patterns of sympathetic discharge can be identified during the pressor response. A differential pattern consisting of an increase in renal nerve activity and no change in sympathetic activity to skeletal muscle vasculature can be elicited from sites ventromedial to the caudal pole of the facial nucleus. From more lateral and caudal sites, a generalized sympatho-excitation is evoked in the outflow to both the kidney and hindlimb muscle vasculature. A third response consisting of a differential increase in muscle sympathetic activity simultaneous with a small decrease in renal nerve activity could be evoked from caudal sites, lateral to the inferior olives and superficial to the ventral surface. The results show that ventral medullary neurons can selectively activate sympathetic outflow to control specific vascular beds. These data may support the hypothesis that the ventrolateral medulla contains discrete groups of topographically arranged neurons that can differentially control sympathetic tone to various end-organs. PMID- 1593090 TI - Fundamental rhythm of renal sympathetic nerve activity in anesthetized cats. AB - To examine the fundamental rhythms of sympathetic discharges, the periodicity of synchronized renal nerve activity (RNA) was measured in anesthetized cats. After filtering the RNA between 50-3000 Hz, rectification and integration the periodicity was calculated by measuring the peak to peak intervals. Two major periodicities were detected, a Tc rhythm between 6 and 25 c/s with a 43% probability and a Tb rhythm between 2 and 6 c/s with a 57% probability. The mean periods of Tc and Tb were 95 +/- 2 ms and 297 +/- 4 ms (+/- SE) respectively. Another techniques which has previously been used to assess the periodicity was also applied, in which the original neurogram was filtered between 0.08-3000 Hz and measured by power spectral analysis. However, this technique only identified the 2-6 c/s frequency and the faster Tc rhythm was undetected. Baroreceptor stimulation induced by noradrenaline decreased the probability of Tc and Tb modal components. Baroreceptor denervation led to an increase in the probability of the Tc rhythm and reduction in the Tb rhythm. These results support our model that the Tc rhythm reflects a fundamental periodicity of central origin and that the Tb rhythm reflects a periodicity of cardiac-related RNA, which is produced by reflex inhibition of the fundamental rhythm by periodic baroreceptor input. PMID- 1593091 TI - Effect of chemoreceptor stimulation on the periodicity of renal sympathetic nerve activity in anesthetized cats. AB - The effect of chemoreceptor stimulation, with asphyxia (1 min), hypoxia (2 min) or hypercapnia (2 min), on the periodicity of synchronized renal sympathetic nerve activity (RNA) was examined in anesthetized cats before and after peripheral chemoreceptor and baroreceptor denervation. RNA was filtered between 50-3000 Hz, rectified and integrated. Time intervals, less than 500 ms, between synchronized interburst intervals were measured and used to produce periodicity histograms. Under control normoxia two major periodicities were evident, a Tc rhythm between 6 and 17 c/s comprising 34 +/- 5% (+/- SE) of measured intervals and a Tb rhythm between 2 and 6 c/s with a 66% probability. The mean periods of Tc and Tb were 110 +/- 6 ms and 299 +/- 7 ms respectively. The periodicity distribution and mean Tc and Tb rhythms for RNA discharge under various chemoreceptor stimulations were not significantly changed despite significant increases in arterial blood pressure in all cases. The amplitude and overall number of synchronized RNA peaks were however increased with chemoreceptor stimulation. When asphyxia was applied under a constant arterial pressure the periodicity of synchronized RNA still was not significantly altered. Baroreceptor and peripheral chemoreceptor denervation led to an increase in the probability of the Tc mode and reduction in the Tb mode, once again the application of chemoreceptor stimulation did not significantly alter the frequency distribution of synchronized RNA. The results indicate that chemoreceptor stimulation does not affect the 10 c/s fundamental rhythm and the stability of gate operators altering Tc/Tb proportions, although it can alter the number of active fibres and interacts with the baroreflexes to maintain RNA at elevated blood pressures. The results support our model that the Tc mode reflects a fundamental periodicity of central origin and the Tb mode a periodicity of cardiac related RNA, which is produced by the opening and closing of gate operators to the fundamental rhythm. PMID- 1593092 TI - Sources of anterior gastric vagal efferent discharge in rats: an electrophysiological study. AB - The source of vagal efferent discharge (VED) in the anterior branch of the gastric vagus was investigated in urethane-chloralose anesthetized rats using successive and selective vagal cuts. After cutting the right cervical vagus, the basal VEDs were increased in 15 out of 21 cases by 4-53% (median 18%). After both cervical vagi were cut, VEDs were reduced by 10-95% (median 90%) in 14 of 17 experiments and a subcervical basal VED was observed in all rats. Additional cut of the distal end of the anterior gastric branch did not induce a consistent effect. A small segment of subdiaphragmatic anterior gastric vagus (4-5 mm) was further isolated by a fourth cut at the proximal end of the anterior gastric vagus; abolition of the subcervical VED occurred in only 4 of 14 successful cuts whereas in the other 10 experiments, the VED was reduced by 38-94% (median 87%). Histological examination revealed the presence of neurons in a paraganglion lying within the isolated nerve segment. These findings indicate that the stomach not only receives VED descending directly from medullary vagal motor neurons (about 90%), but also (approximately 10%) from neural elements located between subcervical to upper abdomen levels (the 'subcervical VED') and/or between the bifurcation of the accessory celiac branch to the gastro-esophageal junction (the 'residual VED'). In rats there is little crossed gastric vagal innervation, in agreement with anatomical observations, although there is a robust inhibitory influence from contralateral vagal afferents on medullary vagal motor neurons. PMID- 1593094 TI - Characterization and growth response of bacteria in soil following application of carbofuran. AB - Enhanced biodegradation of carbofuran (2, 3-dihydro-2, 2 dimethyl-7-benzofuranyl methyl carbamate) is an economically significant, but poorly understood, microbial phenomenon in soil. A series of experiments was conducted to examine short term changes in soil bacterial populations stimulated by carbofuran application at field rates. In the field experiment, commercially formulated carbofuran and butylate (S-ethyl diisobutyl carbamothioate) were applied at 5.6 kg ai ha-1 and 8.4 kg ai ha-1, respectively, on a soil (Putnam silt loam) exhibiting enhanced degradation of carbofuran. In laboratory studies, technical grade carbofuran (20 mg kg-1 soil) was applied to samples of the field soil. Bacterial populations were estimated using non-selective (tryptic soy agar) and selective media containing carbofuran or butylate. Largest population increases in pesticide-treated soil were observed between 7 and 15 days after treatment (DAT) compared to populations in non-treated soil. Significant increases (P less than 0.05) in total bacterial populations and presumed carbofuran-degraders due to carbofuran application were associated with increased populations of Pseudomonas spp. and Flavobacterium spp. Application of carbofuran appeared to provide a competitive advantage to these species over actinomycetes persisting beyond 20 DAT. Growth responses of bacteria to carbofuran in the Putnam soil were compared to those in a native prairie soil (Mexico silt loam), which exhibited a much slower rate of carbofuran degradation. Bacterial population response to carbofuran was measurable, but small and short-lived. Perpetuation of the enhanced degradation phenomenon may lie in a persistent pesticide-induced competitive advantage given to a very small segment of the microbial population. This advantage may not be detectable after 20 days using conventional plating techniques. PMID- 1593093 TI - Bioavailability, biological activity and characterization of bound residues of diflubenzuron in wheat. AB - Wheat grain was treated with radiolabeled diflubenzuron at 100 ppm and stored for various periods; up to 6 months. The grain was surface washed, Soxhlet-extracted with methanol, and the residues determined. A relative constant amount of bound residues (4%), i.e., non-extractable radioactivity, was found 4 months after application and remained constant. More than 97% of the extractable radioactivity in the grain after 6 months was identified as diflubenzuron. When the bound residues were fed to rats, 47% of the administered dose was eliminated via the urine and the remainder via feces within 96 h. Diflubenzuron was the major component in the urine. Adding bound residues to housefly media resulted in a dose-dependent mortality of housefly pupae. Bound residues were biologically active, preventing the emergence of adult houseflies. Supercritical fluid extraction of the bound residues extracted 92% and 96% of the radioactivity associated with grain and feces, respectively. Only diflubenzuron was present in these extracts. The bioavailability and biological activity of bound residues of diflubenzuron have been demonstrated and the identity of the radioactivity was shown to be parent compound. Based on these findings, bound pesticide residues can no longer be ignored or overlooked in the evaluation of pesticide residues and their possible toxicological implications. PMID- 1593095 TI - Endosulfan and diazinon toxicity to the freshwater rotifer Brachionus calyciflorus. AB - The acute toxicity of endosulfan and diazinon to the freshwater rotifer Brachionus calyciflorus was determined after 24 hours exposure to these toxicants. The mean 24 hr-LC50 values were 5.15 and 29.22 mg/L for endosulfan and diazinon respectively. Based on these results, four sublethal concentrations were chosen to determined the median lethal time (LT50) at each concentration of toxicant tested. We also used a control with the solvent (acetone). The concentration tested were 1/5, 1/4, 1/2 and 2/3th LC50 (24hr) for both pesticides. We found a decrease in the median lethal time (LT50) with increasing pesticide concentrations. The LT50 values ranged from 6.49 to 3.48 days after endosulfan treatment, and from 6.96 to 2.49 days after diazinon exposure. No effects on survival were observed in control animals exposed to the solvent. PMID- 1593096 TI - Acute toxicity, uptake and clearance of diazinon by the European eel, Anguilla anguilla (L.). AB - The toxicity, accumulation, and elimination of diazinon were investigated for the european eel, Anguilla anguilla. The 24, 48, 72 and 96-h median lethal concentrations (LC50) were 0.16, 0.11, 0.09 and 0.08 mg/L, respectively. Fish exposed to sublethal concentration (0.042 mg/L) accumulated diazinon in liver and muscle tissues. Bioconcentration factors (BCF) of diazinon were 1850 in liver, and 775 in muscle over the 96-h exposure period. Upon removal from diazinon containing water the contaminated fish rapidly eliminated diazinon. The excretion rate constants of this insecticide were 0.108 h-1 for liver and 0.016 h-1 for muscle. Diazinon half-lives were 16.6 and 33.2 hours for liver and muscle, respectively. PMID- 1593097 TI - Body Substance Isolation. PMID- 1593098 TI - Vancomycin-resistant bacteria. PMID- 1593099 TI - A cluster of vancomycin-resistant Enterococcus faecium in an intensive care unit. AB - OBJECTIVE: To describe the epidemiology of a cluster of vancomycin-resistant Enterococcus faecium (VAREC) in a cardiothoracic surgery intensive care unit. DESIGN: A case series of patients identified through review of surveillance data on nosocomial infections, review of microbiologic records, and culture survey of patients in the unit. RESULTS: Six patients in the cardiothoracic surgery intensive care unit had VAREC with identical antimicrobic susceptibility patterns over a 6-month period. Four patients were identified with VAREC through prospective surveillance and 2 through retrospective review. Prior vancomycin use was seen more commonly in patients with VAREC (6/6, 100%) than in those without VAREC (3/12, 25%) (Fisher's exact test, p = .01). Six of the 7 patients with prior infection developed VAREC (85.7%). A prior nosocomial infection and prior exposure to vancomycin were found to be important variables in a logistic regression analysis. VAREC also was isolated from the environment. A combination of cohorting of patients and staff, and modifications of standard contact isolation practices eliminated the presence of VAREC from the cardiothoracic surgery intensive care unit. CONCLUSIONS: The results suggest that prior administration of vancomycin, especially in the patient who develops nosocomial infection, can influence the acquisition of vancomycin-resistant enterococci and that VAREC may be transmitted from patient to patient. Using a modification of the standard infection control practice of isolation, we were able to control the spread of this resistant strain of E faecium. PMID- 1593100 TI - Risk factors for epidemic Xanthomonas maltophilia infection/colonization in intensive care unit patients. AB - OBJECTIVE: To determine risk factors for and modes of transmission of Xanthomonas maltophilia infection/colonization. DESIGN: Surveillance and cohort study. SETTING: A 470-bed tertiary trauma-referral community hospital. PATIENTS: From January 1, 1988 to March 17, 1989, 106 intensive care unit patients developed X maltophilia infection/colonization. We defined a case as any intensive care unit patient who, from July 15, 1988, through March 17, 1989 (epidemic period), had X maltophilia infection/colonization greater than or equal to 48 hours after intensive care unit admission. We identified 45 case patients and 103 control patients (persons in the shock-trauma intensive care unit for greater than or equal to 72 hours during the epidemic period who had no X maltophilia-positive culture). RESULTS: Cases were significantly more likely to occur in the shock trauma intensive care unit than in all other intensive care units combined. Mechanical ventilation, tracheostomy, being transported to the hospital by airplane, and receipt of a higher mean number of antimicrobials were risk factors for X maltophilia infection/colonization. Risk of X maltophilia infection/colonization was significantly greater among cases exposed to a patient with a X maltophilia surgical wound infection than among those without such exposure (relative risk = 1.3, p = .03). Animate and inanimate cultures revealed X maltophilia contamination of the hospital room of a patient with an X maltophilia surgical wound infection, of respiratory therapy equipment in this patient's room, of respirometers shared between patients, and of shock-trauma intensive care unit personnel's hands. Related environmental and clinical isolates were serotype 10. CONCLUSIONS: Mechanically ventilated patients receiving antimicrobials in the shock-trauma intensive care unit were at increased risk of X maltophilia infection/colonization. Patients with draining X maltophilia surgical wound infections served as reservoirs for X maltophilia, and contamination of the respirometers and the hands of shock-trauma intensive care unit personnel resulted in patient-to-patient transmission of X maltophilia. PMID- 1593101 TI - Determinants of clean surgical wound infections for breast procedures at an oncology center. AB - OBJECTIVE: To determine the clean surgical wound infection rate for breast procedures and the risk factors predisposing patients to these infections. DESIGN: A survey study. SETTING: Oncology center. PATIENTS: A consecutive sample of adult female patients who underwent surgical breast procedures for suspected carcinoma of the breast. Patients undergoing excisional biopsy, lumpectomy, or mastectomy from January 1985 to January 1987 were included in the study. INTERVENTION: Clean surgical wound infection rates were derived overall and for each procedure type. The medical records of all patients were then reviewed to extract data on patient characteristics and operative information in order to assess the risk factors for infection. RESULTS: Among the breast procedures performed on 448 patients, the overall clean surgical wound infection rate was 8.7% (39/448). The clean surgical wound infection rate for each procedure type was as follows: biopsy 2.3%, lumpectomy 6.6%, and mastectomy 19%. In addition to the type of procedure, factors significantly (p less than .05) associated with the development of clean surgical wound infection in the univariate analysis included: presence of surgical drains (p less than .01); closed suction drainage (odds ratio [OR] = 16.5, 95% confidence interval [CI95] = 5.0-54.7); location of the drain (OR = 3.3, CI95 = 1.7-6.6); prolonged preoperative stay (OR = 1.2, CI95 = 1.0-1.5); length of surgery (OR = 2.2, CI95 = 1.7-3.0); and greater mean age (OR = 1.6, CI95 = 1.2-2.1). CONCLUSION: Clean surgical wound infections are not uncommon in patients undergoing breast procedures. Factors relating to both the patient and operative techniques contribute to the clean surgical wound infection rate. Further consideration should be given to perioperative antibiotic prophylaxis for selected breast procedures, and the role of surgical drains should be reassessed. PMID- 1593102 TI - Impact of central venous catheter removal on the recurrence of catheter-related coagulase-negative staphylococcal bacteremia. AB - OBJECTIVE: To determine the impact of catheter management on the acute and long term outcome of catheter-related coagulase-negative staphylococcal bacteremia. DESIGN: Retrospective surveillance of catheter-related sepsis using quantitative blood and catheter cultures. SETTING: University-affiliated tertiary cancer center. PATIENTS AND METHODS: Seventy patients with catheter-related coagulase negative staphylococcal bacteremia were studied by retrospective chart review. The clinical characteristics of the patients and the management of the bacteremias were determined. The impact of immunosuppressive risk factors, antibiotic therapy, and catheter management on the recurrence of the bacteremia was investigated. RESULTS: Acute sepsis-related morbidity and mortality were not related to catheter management. However, during a 12-week followup period, the bacteremia recurred in 20% of the patients whose catheters remained in place, compared with only 3% of those whose catheters were removed (p less than .05). By multivariate analysis, patients whose catheters remained in place were 2.9 times more likely to experience a recurrence than those whose catheters were removed (odds ratio = 2.9, 95% confidence interval = 1.2-8.8, p = .03). All other potential risk factors were equally distributed between patients, with and without a recurrence. CONCLUSIONS: Although patients with catheter-related coagulase-negative staphylococcal bacteremia could be treated successfully while the catheter remains in place with the majority remaining free of recurrence, catheter retention results in a significantly higher risk for the recurrence of the bacteremia. PMID- 1593103 TI - Interpersonal communication: a review of eye contact. AB - Because healthcare takes place in the context of an interpersonal relationship, it is important for the healthcare worker to be cognizant of eye contact and the implications eye contact may have on the delivery of patient care. The healthcare worker should consider a variety of factors in evaluating the patient's eye contact including cultural background, emotional state, personality characteristics, and gender. Each patient should be personally assessed and appropriate healthcare strategies planned that meet individual needs. Interpersonal approaches need to be modified on an ongoing basis as the patient provides feedback during the healthcare worker-patient interaction. PMID- 1593105 TI - Changing psychosocial patterns increase American's risk for infection. PMID- 1593104 TI - The application of continuous quality improvement to healthcare. PMID- 1593106 TI - Nosocomial infection and pseudoinfection from contaminated endoscopes could have been avoided. PMID- 1593107 TI - Needlestick prevention: new paradigms for research. PMID- 1593108 TI - Reported hospital needlestick injuries in relation to knowledge/skill, design, and management problems. AB - OBJECTIVES: To investigate reported needlestick injuries in hospital workers from an adult learner theory perspective: identifying safe needle device knowledge and practice, and flaws in needle designs and management practices surrounding such problems. DESIGN: Exploratory descriptive study of reported needlestick injuries from hollow needled devices in a hospital. Injured healthcare workers were counseled via hospital protocol, then a survey was filled out containing no identifiers of individual or institution. SETTING: Seventeen Metropolitan Washington, DC, area hospitals. PARTICIPANTS: All workers reporting needlestick injuries during February 1-28, 1990. RESULTS: Seventy-two injuries were reported; there were no multiple injuries to any individual. Thirty-three (45.8%) were to registered nurses (RNs)-more than any other group of workers. Recapping accounted for a higher percentage than any other activity (10 sticks, 14.1%). Of workers incurring recapping injuries, 3 identified a knowledge of a one-handed spearing technique and did not practice it; 4 neither knew nor practiced it. Eighteen (25.0%) were to "down-stream" housekeepers and aides who did not use such devices in their practice. Disposable needle/syringes caused 49.3% of injuries; hypodermic needles on intravenous lines caused 16.9%. Of the needlesticks, 60.6% were after use and before disposal, 4.2% occurred as the worker was putting an item into a needlebox, and 9.9% occurred from needles protruding from inappropriate bags. Many injuries occurred in the first 2 hours of work after being off the previous day, on Sunday, and on Monday. CONCLUSIONS: Of nurses and medical technologists reporting knowledge of a spearing recapping technique, 97.3% suffered injury via other methods. This strongly suggests that knowledge leads to different action. Safer needled devices and needle-free systems would make a safer workplace. Further study is indicated to identify if and why the first two hours after returning to work on Sunday or Monday are risky for needlestick injuries. Management practices must ensure compliance to safe practice both by employees and related medical staff. PMID- 1593109 TI - A five-year study of needlestick injuries: significant reduction associated with communication, education, and convenient placement of sharps containers. AB - OBJECTIVE: To decrease the numbers of needlesticks among healthcare workers. DESIGN: All reported needlestick injuries at Santa Clara Valley Medical Center, San Jose, California, were reviewed, analyzed, and tabulated by the infection control department yearly from 1986 to 1990. SETTING: A 588-bed county teaching hospital in San Jose, California, affiliated with Stanford University. PARTICIPANTS: All employees of Santa Clara Valley Medical Center who reported needlestick injuries on injury report forms. INTERVENTIONS: From April to December 1987, more needle disposal containers were added to as many patient care areas and as close to the area of use as possible. Results of 1986, 1988, 1989, and 1990 analyses were communicated yearly to all personnel, extensive educational programs were conducted in 1987 and 1988, and educational efforts continued in 1989 and 1990. RESULTS: In 1986, there were 259 needlestick injuries at our institution, 22% (32) from recapping. After needle disposal containers were added to all patient care areas, needlestick injuries for 1988 totalled 143, a 45% decrease in the total needlestick injuries and a 53% decrease in recapping injuries. Communication of results to all areas of the hospital and educational activities were started in 1987 and continued through the next 3 years. In 1989, there were 135 needlestick injuries, a decrease of 6% from 1988; recapping injuries decreased 40% from 1988. In 1990, there were 104 needlestick injuries, a 23% decrease since 1989, and a 33% decrease in recapping injuries. The total number of needlestick injuries from 1986 to 1990 decreased by 60%, and those injuries from recapping decreased by 81% to 89%. CONCLUSIONS: We have continued to monitor needlestick injuries, communicate findings to all personnel, and include needlestick prevention in educational programs. We contend that more convenient placement of needle disposal containers, communication of findings, and education do decrease needlestick injuries in healthcare workers. PMID- 1593110 TI - Prevention of infectious diseases in ambulatory care: immunoprophylaxis and chemoprophylaxis. AB - OBJECTIVE: To review the current recommendations for immunoprophylaxis and chemoprophylaxis of infection in adults, including those who are at increased risk from occupation, lifestyle, travel, or pre-existing medical conditions. DESIGN: Review of the pertinent literature. SETTING: Adult ambulatory care. CONCLUSIONS: Guidelines for the prevention of several diseases including measles, tuberculosis, and bacterial endocarditis recently have been changed. Current recommendations for immunization, immune globulin therapy, and chemotherapy for these and other common infections are reviewed. PMID- 1593111 TI - Continuous quality improvement in a hospital system: implications for hospital epidemiology. PMID- 1593112 TI - Needlestick prevention devices: a pointed discussion. PMID- 1593113 TI - Bland soap handwash or hand antisepsis? The pressing need for clarity. PMID- 1593114 TI - Exhibit to explore history of pharmacy. PMID- 1593115 TI - Policies on HIV testing explained. PMID- 1593116 TI - Concern for patients helps physicians avoid lawsuit. Interview by Bob Carlson. PMID- 1593117 TI - HIV provider referral proves effective. PMID- 1593118 TI - Staff development: making one plus one equal three. PMID- 1593119 TI - New bloodborne pathogens rules become effective. PMID- 1593120 TI - Indiana residents polled on insurance, malpractice. AB - The Indiana State Medical Association contracted with The Gallup Organization, Inc. of Princeton, N.J., to conduct a statewide assessment of Indiana households regarding attitudes and behaviors toward health care services and issues. Telephone interviews of 1,010 randomly selected adult heads of households were conducted in August 1991. At the 91% level of confidence, the maximum expected error range for a sample of 1,010 respondents is +/- 3.1%. Data were analyzed across key demographics including respondent age, race and geographic location. In addition, counties were classified as urban, rural or "mixed" (those in which a substantial metropolitan area was set in an overall rural area). PMID- 1593121 TI - Coronary-subclavian steal as a cause of dyspnea. PMID- 1593122 TI - Pharmacists used pill-tiles, machines. PMID- 1593123 TI - Introduction of lithography advances medical illustration. PMID- 1593124 TI - "Midnight clerks and daily drudges": hospital psychiatry in New York State, 1890 1905. PMID- 1593125 TI - William Beaumont, M.D. and malpractice: the Mary Dugan Case, 1844. PMID- 1593126 TI - "... the science least adequately studied in England": physiology and the George Henry Lewes studentship, 1879-1939. PMID- 1593127 TI - More than a coincidence? The arrival of arsenic and the disappearance of plaque in early modern Europe. PMID- 1593128 TI - John B. de C. M. Saunders, (1903-1991). PMID- 1593129 TI - Was William Harvey's coat of arms at Padua an early example of the medical use of the caduceus? PMID- 1593130 TI - Freeze-thaw effects on the detection of blood group substances in detergent extracts by enzyme-linked immunosorbent assays (ELISA). AB - The sensitivity of an enzyme-linked immunosorbent assay (ELISA) for human blood group antigens extracted from blood stains with the surfactant, n-octyl-beta-D glucopyranoside (OBG), at concentrations below the critical micelle concentration can be increased by the introduction of a single freeze-thaw step. The ELISA signals increase from 3- to 4-fold for OBG extracts of 80 nl bloodstains. The ELISA signal enhancement occurs irrespective of the age of the bloodstains, at least for bloodstains up to 1 year old. The origin of the effect has been investigated and its is demonstrated that the freeze-thawing cycle increases the extent of adsorption of the blood group determinants in OBG-solubilized complexes onto microtitre plates. Gel filtration has been used to analyse the composition of OBG extracts of bloodstains in terms of the carriers of the blood group substances, protein and phospholipid in fresh and freeze-thawed extracts. It was found that freeze-thawing alters the distribution of blood group active material in the lipid-protein OBG complexes leading to a greater proportion of blood group active material in higher molecular weight complexes. The freeze-thaw effect is eliminated on the addition of a cryoprotectant, such as glycerol, and the factors which contribute to changes in the microstructure of OBG extracts on freeze thawing are discussed. PMID- 1593131 TI - Flow cytometry analysis of the expression of neutrophil FMLP receptors. AB - The number of cell surface FMLP receptors expressed by peripheral blood neutrophils taken from healthy individuals was quantitated using a direct fluorescence label analysed on the FACScan. Receptor numbers, assayed on cells from heparinised blood prepared at 4 degrees C or 37 degrees C or in the presence of LPS (30 ng/ml) were 12,540 +/- SD 2413, 18,588 +/- 4938 and 45,041 +/- 10,744 respectively. Anticoagulation with EGTA resulted in 25-30% greater basal receptor numbers but had no effect on receptor level after maximal stimulation with LPS. Double labelling with a neutrophil-specific mAb showed that the entire neutrophil population expressed FMLP receptors. PMID- 1593132 TI - Application of phase partitioning and thiophilic adsorption chromatography to the purification of monoclonal antibodies from cell culture fluid. AB - A two-step method for the isolation of an IgG1 monoclonal antibody against horseradish peroxidase from hybridoma cell culture supernatant is described. Purification was achieved using an aqueous two-phase extraction procedure in conjunction with thiophilic adsorption chromatography. In an aqueous two-phase system composed of 5% PEG 1540 and 22% phosphate the monoclonal antibody preferentially associates with the PEG-rich top phase whereas proteins such as albumin and transferrin partition into the salt-rich bottom phase. Final purification of the monoclonal antibody was achieved by subjecting the PEG-rich top phase to thiophilic adsorption chromatography. The monoclonal antibody purified to homogeneity retained its specificity for horseradish peroxidase as revealed by polyacrylamide gel electrophoresis and an enzyme-linked immunosorbent assay. The potential of this purification protocol for large scale applications is discussed. PMID- 1593133 TI - Assessment of neutrophil chemotaxis by laser and video densitometry. AB - A laser densitometer and a video densitometer were used to evaluate neutrophil chemotaxis slides which were also assessed by the standard microscopic technique. A linear relationship was observed between cell number per high power field (HPF) and peak height by laser densitometry (r2 = 0.66) or peak area by video densitometry (r2 = 0.81). For wells containing more than 20 cells/HPF the least variability was observed with video densitometry. Quantitative results from neutrophil chemotaxis assays performed in 48-well microchambers can be obtained rapidly and conveniently by the use of commercially available video densitometers. PMID- 1593134 TI - An immunochemical approach to investigating the mechanism of inhibition of cysteine proteinases by members of the cystatin superfamily. AB - Antibodies were raised against a synthetic dodecameric peptide KGAGQVVAGPWK (K12K), encompassing sequences thought to be important for the function of the cysteine proteinase inhibitors of the cystatin superfamily. These antibodies specifically recognized molecules of family 3, i.e., kininogens, in the serum of seven mammalian species tested in this study. The only notable exception was that of rat thiostatin (T kininogen) which is structurally related to the kininogen family. The antibodies also discriminated between family 2 (cystatins) and family 3 (kininogens) of the cystatin superfamily, since neither chicken cystatin nor human and rat cystatins C and S, which all belong to family 2 were recognized. The cystatin-like inhibitory domains resulting from fragmentation of human low molecular weight kininogen by bovine trypsin, were still recognized by antibodies, indicating that discrimination does not require two neighbouring inhibitory sites on the kininogen heavy chain. The antibodies blocked the capacity of kininogens to inhibit papain, suggesting that they recognize a conformational epitope at or near the kininogen inhibitory sites. The inhibitory properties of family 2 cystatins remained unchanged, confirming that members of this family do not interact with anti K12K antibodies. These antibodies are thus a new tool able to discriminate functionally and structurally between the members of the cystatin superfamily. PMID- 1593135 TI - A sensitive enzyme-linked immunosorbent assay for human interleukin-8. AB - In order to quantify human interleukin-8 (IL-8), which is chemotactic for T cells and basophils as well as neutrophils, we developed an enzyme-linked immunosorbent assay (ELISA). Since binding inhibition tests indicated that three monoclonal antibodies (mAbs; BS-1, WS-4, WS-6) blocked the binding of 125I-labelled IL-8 to neutrophils, we tested an ELISA using these mAbs as primary antibodies, rabbit anti-IL-8 Ab as the secondary antibody, and alkaline phosphatase-labelled goat anti-rabbit Ab as the conjugate. Among the three mAbs tested, WS-4 was the most sensitive with a detection limit of 16 pg/ml. Several other cytokines, including monocyte chemotactic and activating factor (MCAF), which is structurally related to IL-8, showed no cross-reactivity in this system, indicating that this ELISA is specific for IL-8. The coefficients of variation for the intra- and interassays were below 10%. Furthermore, this ELISA also detected natural IL-8 (including both 72 and 77 amino acid forms) produced by cultured human cells and cell lines stimulated with IL-1, suggesting that this system will be useful in the detection of natural IL-8 in various body fluids. PMID- 1593136 TI - Europium-labelled streptavidin as a highly sensitive universal label. Indirect time-resolved immunofluorometry of FSH and TSH. AB - Labelling of streptavidin with a fluorogenic europium ion was optimized with the aim of obtaining a universal, stable and highly sensitive non-isotopic label for time-resolved fluorometric immunoassays (TR-FIA) based on dissociative fluorescence enhancement (DELFIA). Even the conjugation of all the free amino groups of streptavidin with Eu chelates had only a minor effect on the binding capacity of the protein or its affinity. The labelled streptavidin was evaluated in indirect time-resolved immunofluorometric assays of human follicle and thyroid stimulating hormones (FSH and TSH). The interassay imprecision was below 3% within the concentration range from 2.5 to 94 U/l for the FSH samples and below 5% in the range from 2.4 to 35 mIU/l for the TSH samples. The detection limits of the assays for FSH and TSH were 0.05-0.10 U/l and 0.01-0.025 mIU/l, respectively, when a CV of 15% was regarded as the acceptable upper limit of imprecision. The results obtained by the indirect assays correlated closely with those obtained by corresponding direct sandwich assays. The model assays demonstrated the utility of Eu-labelled streptavidin as a universal reagent for immunoassays requiring a wide dynamic range and high sensitivity. PMID- 1593137 TI - The use of [35S]methionine as a target cell label in long term cytotoxic assays. AB - Cytotoxic killing assays represent an important experimental tool in immunology to determine specific and/or cross-killing activities of immune effector cells in vitro. To evaluate the killing capacity of effector cells using cytotoxic killing assays, target cells are prelabeled with a radioisotope. Present labeling methods, using 51chromium to prelabel target cells, are associated with some disadvantages. In this study, we tested the use of 35sulfur-methionine ([35S]methionine) to prelabel target cells in long term cytotoxic killing assays. Our results indicate that prelabeling of target cells with [35S]methionine allows the use of a smaller amount of target and effector cells and enables more accurate detection of target cell killing, compared to the presently used labeling methods. PMID- 1593138 TI - Coagulation disorder following viper bite in Orissa. AB - Forty-three cases of viper bite were studied for coagulation disorder of which 34 (79.1%) cases had bleeding manifestations from one or more sites, haematuria being the commonest (46.5%). Disseminated intravascular coagulation was the predominant coagulation abnormality. Administration of snake venom antiserum resulted in prompt recovery from coagulation disorder. However, natural recovery from coagulation abnormality did occur though took longer time. PMID- 1593139 TI - Aetiological studies on hospital inpatients with secretory diarrhoea in Calcutta. AB - Twenty-five cases of all age groups with secretory diarrhoea admitted to the Infectious Diseases Hospital, Calcutta were studied. Bacterial enteropathogens were detected by bacteriological examination of the faeces, in each and every case. The main pathogens detected were Escherichia coli and Vibrio cholerae. V cholerae was more commonly associated with severe illness except in the very young, while Esch coli was equally associated with moderate and severe illness. Multiple isolates were more commonly associated with severe illness and single isolates were more common in illness of moderate severity. PMID- 1593140 TI - Primary chondrosarcoma of the breast. PMID- 1593141 TI - Multiple primary cancers involving hypopharynx and middle oesophagus. PMID- 1593143 TI - Total intravenous anaesthesia--its scope in developing countries. PMID- 1593142 TI - Obstetrics--past and present (a comparative review of 210 cases of obstructed labour). PMID- 1593144 TI - Undergraduate teaching in anaesthesia. PMID- 1593145 TI - Intrathecal buprenorphine for postoperative analgesia in orthopaedic surgery. AB - Sixty patients aged 50-65 years randomly received intrathecally either hyperbaric bupivacaine hydrochloride (one ml) in group A (30 cases) or bupivacaine hydrochloride (one ml) and buprenorphine 300 micrograms in combination in group B (30 cases). They were all scheduled for orthopaedic operations in the lower limbs. Prolonged postoperative analgesia, minimal disturbance of consciousness and respiration were observed in the group that received buprenorphine. The only side-effect found in the buprenorphine group was nausea and vomiting in 10 patients. This study shows that buprenorphine is an effective analgesic suitable for the management of postoperative pain in elderly patients. PMID- 1593146 TI - Evaluation of haemotherapy in thalassaemias (20 years of Indian experience). AB - Two hundred fifty-one patients of beta-thalassaemia ranging from 3 months to 15 years of age were evaluated. They were maintained on hypertransfusion regimen and received periodic transfusions of group specific packed red cells. These multiple transfused patients were subjected to the tests for detection of transfusion malaria, HBsAg and allo-antibodies against red cells. Malaria infection and HBsAg were detected in 6.4% and 15.5% of patients respectively, while allo-antibodies were detected in 15.5% of patients. Thirteen patients (5.18%) developed hypersplenism and associated pressure symptoms due to splenomegaly for which they underwent splenectomy. Postsplenectomy period was uneventful and showed marked decrease in the frequency and quantitative requirements of transfusions and overall improvement in health. The continuing steady improvement of the prognosis in thalassaemia secondary to hypertransfusion regimen required us to transfer attention to other problems involved in thalassaemia management such as problems of hypersplenism and problems of multiple transfusion. PMID- 1593147 TI - Eating epilepsy: a study of twenty cases. AB - Twenty cases of eating epilepsy have been studied over a period of 5 years (1985 1989). Males outnumbered females (4:1). Heavy meal comprising conventional Indian diet (viz, rice, vegetables, etc), was found to be the most important provocating factor (14 out of 20 cases). The attacks occurred at lunch time in most cases (15). Thirteen cases had generalised seizures. Electro-encephalogram showed focal changes in 10 cases, generalised changes in 6 cases, while 4 cases had normal electro-encephalogram. Computerised tomography scan was normal in all the cases (7) when it was done. PMID- 1593149 TI - Acyclovir bioavailability in human skin. AB - Clinical experience demonstrates that oral acyclovir (ACV) is superior to topical ACV in treating recurrent cutaneous herpes simplex virus type 1 (HSV-1) infections. Cutaneous HSV-1 infections are complex in their pathology, affecting the basal epidermis in skin as well as establishing a latency phase in sensory ganglia. In vitro and in vivo human skin model systems were used in the present study to quantitate ACV disposition and absorption in skin and blood following two routes of administration and to investigate whether bioavailability differences were the result of insufficient drug delivery. Physiochemical and physiologic parameters determined from these experiments were used to develop a mathematical model to predict ACV disposition and absorption in human subjects. Model predictions and in vivo data agree; topical administration of commercial 5% ACV ointment and cream result in a 48 times greater total epidermal ACV concentration than after oral administration. Mathematical modeling of the ACV concentration gradient through the epidermis revealed, however, that the drug concentration in the target site of HSV-1 infections, the basal epidermis, is 2-3 times less after topical administration than after oral administration. Thus, the observed lack of clinical efficacy with topical ACV therapy in the recurring HSV 1 infection likely reflects the insufficient delivery of the drug to the target site of the HSV-1 infection, the basal epidermis. PMID- 1593148 TI - Environmental risk factors in endemic pemphigus foliaceus (Fogo selvagem). "The Cooperative Group on Fogo Selvagem Research". AB - Endemic pemphigus foliaceus or Fogo selvagem (FS) is an epidermal organ-specific autoimmune disease mediated by autoantibodies. Individuals at risk are peasants who live and work on farms located in the interior of certain endemic states of Brazil. This case-control study compares a group of 52 FS patients with 52 patients suffering from other dermatoses admitted and followed at the hospital for pemphigus (Hospital do Penfigo) in the city of Goiania, state of Goias. Patients and controls matched 1:1 by age, sex, and occupation were examined by two dermatologists at the time of admission and asked to respond to a prepared questionnaire. This questionnaire concerned current and past (1 and 5 years) exposure to environmental risk factors. The following risk factors were assessed: black fly bites, presence of rodents at home, exposure to cereal dust, exposure to fumes or dust released by tree and shrub removal, and exposure to insecticides. Relative risks were estimated from tabulated data by the odds ratio and tested for significance by the chi-square test. The 95% confidence interval for the odds ratio was also calculated for each of the risk factors. The only risk factor showing an odds ratio significantly different from one was exposure to simuliidae bites (odds ratio 4.7, p less than 0.001). This study reinforces the hypothesis that chronic exposure to black fly antigens may precipitate IgG4 antibody formation in predisposed individuals. These antibodies in turn may cross react with epidermal antigens and cause acantholysis and the clinical expression of the disease known as FS. PMID- 1593150 TI - Analysis of effects of ultraviolet B radiation on induction of primary allergic reactions. AB - Acute, low-dose exposure to UVB light reveals a genetic polymorphism in humans with respect to the ability of irradiated skin to support the induction of contact hypersensitivity (CH) to dinitrochlorobenzene (DNCB). In healthy adult caucasians, as well as in humans with deeply pigmented skin, approximately 45% fail to develop CH when DNCB is painted on UVB-irradiated skin; these individuals are termed "UVB susceptible" (UVB-S), whereas those who develop CH at the challenge site are termed "UVB resistant" (UVB-R). The UVB-S trait is characteristic of virtually all patients with biopsy-proved basal/squamous cell cancer, and may therefore be a risk factor for this disease. We have investigated the effects of UVB on expression of primary allergic reactions (PAR) in healthy caucasian and black-skinned adults, as well as patients with skin cancer. Among UVB-R caucasians, very few (less than 25%) developed PAR at site exposed to UVB, whereas among black-skinned UVB-R subjects, all displayed a PAR at the UVB irradiated site. To determine whether the lack of PAR in UVB-R caucasian subjects was systemic or local in origin, DNCB was applied to UVB-exposed buttock skin, and each individual was then challenged with dilute DNCB on forearm skin twice: 11 and 30 d thereafter. When inflammatory responses were evaluated at the original hapten application site, as well as both challenge sites, complete concordance was observed between positive challenge reactions at 30 d (UVB-R) and positive challenge reactions at 11 d, whereas only one caucasian subject displayed a PAR at 12 d. Thus, UVB-R caucasians can display CH as early as 11 d following hapten application to UVB-treated skin, indicating that their failure to display PAR is a local, rather than a systemic, effect of UVB. Because UVB induced phototoxicity was significantly greater in caucasian than in deeply pigmented skin, it is anticipated that phototoxicity leads to rapid hapten "washout" from UVB-exposed caucasian skin. We propose that PAR usually do not occur in UVB-treated caucasian skin because insufficient hapten remains at the site to trigger a spontaneous inflammation when systemic hapten-specific immunity emerges. PMID- 1593151 TI - Trichohyalin: purification from porcine tongue epithelium and characterization of the native protein. AB - Trichohyalin, a protein of Mr between 190 and 220 kDa in different species, was first demonstrated in large granules of the inner root sheath and medulla of hair follicles and may provide a matrix for keratin filaments. We have purified trichohyalin in milligram quantities from a citric acid-insoluble fraction derived from pig tongue epithelium. Trichohyalin was extracted under conditions of low ionic strength from the citric acid-insoluble fraction, separated by gel filtration chromatography in buffer containing 1 M NaBr, and concentrated by ion exchange chromatography in buffer containing 4 M urea. The purified material, which is soluble in buffers containing 1 M NaBr, was considered to be trichohyalin because of its characteristic molecular weight and amino acid composition and its localization to hair follicle inner root sheath and medulla by indirect immunofluorescence using antibodies against the purified protein. Immunofluorescence showed that trichohyalin is a major protein of filiform papillae of the tongue. Unlike trichohyalin from other animals examined, the porcine protein is a doublet on SDS polyacrylamide gels of 195 and 210 kDa; both bands are recognized by different antibodies, their two-dimensional peptide maps are nearly identical, and they have nearly identical isoelectric points of about 6.6. Trichohyalin has a Stokes radius of 124 A on gel filtration and a Svedberg constant of 6, consistent with an extended structure. The protein probably associates reversibly in solution, and the native protein we have isolated may be dimeric, because crosslinking of the iodinated purified protein with disuccinimidyl suberate demonstrated the presence of a dimer, which could be dissociated in the presence of high concentrations of urea. Rotary shadowing electron microscopy of the native protein showed a filamentous structure averaging 85 nm in length with a single globular-appearing end-domain. The purification of native trichohyalin provides a basis for future functional studies. PMID- 1593152 TI - Photosensitivity to piroxicam is induced by sensitization to thimerosal and thiosalicylate. AB - Piroxicam (PXM), a nonsteroidal anti-inflammatory drug, has been well known to often induce photosensitive eruptions within a few days after its administration. It has been reported that this photosensitivity correlates well with a positive patch-test reaction to thimerosal (TMS) and also to thiosalicylate (TOS), which is an active hapten of TMS. But it has not yet been concluded whether this correlation is caused by a cross-reaction among the drugs or not. In our experiments, animals contact-sensitized with TMS or TOS developed positive photopatch-test reactions to PXM, and those photocontact-sensitized with PXM had positive patch-test reactions to TMS and TOS. Photosensitive reactions were also induced by UVA irradiation (photo test) performed 90 min after perioral administration of PXM in the animals contact-sensitized with TMS or TOS. Analysis of the UVA-treated PXM by nuclear magnetic resonance spectrography and thin-layer chromatography revealed that the high dose of UVA induced photodecomposition of PXM, and generated several other chemicals different from PXM. But the PXM treated with the high dose of UVA could not induce positive patch-test reactions in many of the animals contact-sensitized with TMS or TOS. The cross-reacting hapten generated from PXM by UVA treatment may not be stable in the absence of carrier proteins. These results taken together indicate that the PXM photosensitivity in man is induced by contact-sensitization with TMS, as shown in our animal model, and then is photoallergic in nature. But the identity of the cross-reacting substance remains unknown. PMID- 1593153 TI - Antigen-specific IgG1-mediated epidermal cell injury: a component of contact hypersensitivity reactions in guinea pigs, measurable in vitro in full-thickness skin explants. AB - Guinea pigs were sensitized by the topical application of either dinitrochlorobenzene (DNCB) or oxazolone on days 1, 2, 3, and 10. Seventeen days after the first treatment with the sensitizer, full-thickness 1.0-cm2 explants of untreated areas of skin were topically exposed in vitro to these contactants. Compared to the response of skin from control guinea pigs, skin from specifically sensitized animals showed a dose-related increase in the number of epidermal cells containing vacuoles. A specific increase in epidermal microblistering paralleled the increase in epidermal vacuolization. In addition, skin explants from sensitized animals (exposed to the contactant) showed a specific decrease in the incorporation of [14C]leucine. Full-thickness skin explants from unsensitized guinea pigs were sensitized in vitro by the intradermal injection of serum IgG1 fraction from oxazolone-sensitized guinea pigs. In such passively sensitized explants, the specific contactant produced an increase in the number of epidermal vacuoles, an increase in the amount of microblistering, and a decrease in the number of mast cells detectable by Giemsa staining. To elicit this specific response, the concentration of the specific contactant had to be mildly injurious, as well as antigenic. This requirement for nonspecific injury could be met by topically exposing skin explants to a nonspecific irritant followed by a sub-threshold concentration of the specific contactant. In contrast to vacuole formation and blistering, contactant-specific degranulation of mast cells (measured by the decrease in their number) did not require irritant levels of the contactant. These studies show that several components of contact sensitivity reactions can be reproduced in vitro by the passive transfer of sera containing antigen-specific immunoglobulins. Banks of such sera might, therefore, be useful in identifying (in human populations) many pre-existing sensitivities to chemical compounds. PMID- 1593154 TI - [Radioaerosol inhalation and perfusion imaging studies in immediate postoperative phase after lobectomy]. AB - In order to determine the changes in pulmonary ventilation-perfusion imaging after lobectomies, we examined 11 patients using radioaerosol inhalation and perfusion scintigraphies, before and after the operations. We employed 99mTc labeled albumin aerosol generated by a jet nebulizer for the inhalation imaging, and 99mTc-labeled macroaggregated albumin for the perfusion imaging, respectively. Prior to the operations, there were no (major) defects of imagings on the lung fields. Immediately after the operations, however, we could not detect any abnormal findings on chest roentgenograms, we found detects of imagings on the lung fields in either inhalation or perfusion scintigraphy whose area were mismatching. It took more than 3 weeks for these defects of imagings to disappear. In conclusion, these findings suggest that postoperative hypoxemia might be occurred by these mismatchings. PMID- 1593155 TI - [Clinical evaluation of treatment for prosthetic valve endocarditis and analysis of factors affecting outcome of surgical therapy]. AB - We analyzed the outcome for 18 patients with prosthetic valve endocarditis (PVE) treated between 1965 and 1990, 17 of whom had undergone valve replacement with mechanical prosthetic valves and one of whom had a bioprosthesis. Two patients developed infection within 60 days after surgery, and 16 thereafter. Fifteen patients received combined medical and surgical therapy and three medical therapy. In 14 patients, surgery had been performed during active infection. Mortality rate of those who had received combined medical and surgical therapy was 27%, and that of those who had received medical therapy was 67%. At operation, para-annular abscess was around the mitral prosthesis was found in three patients and around the aortic prosthesis in eight. Seven patients required reoperation for postoperative paravalvular leakage, in six, para-annular abscess had been found at the operation for PVE, and in one para-annular abscess had been noted. One patient who had undergone reoperation had developed reinfection after the first surgery and died due to multiple organ failure after the second operation (Danielson's translocation technique). In one patient who had complete loss of supporting tissue because of severe para-annular abscess, we had performed aortic valve replacement by implanting the aortic valve prosthesis into the left ventricle with Dacron felt-supported sutures placed in the mitral annulus and the muscles of the left ventricular outflow tract. This patient showed no postoperative infection or no paravalvular leakage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593156 TI - [The long-term prognosis of coronary artery bypass surgery--the influence of preoperative left ventricular volume on the prognosis of cardiac death]. AB - We have assessed the long-term prognosis about cardiac death of isolated coronary artery bypass surgery from 1972 to 1988 in 361 consecutive patients. The duration of follow-up were from 0.4 years to 14.6 (mean 5.7) years. Of the 361 study patients, the operative morality was 4.7% (17 patients) and 29 patients (8.0%) died during follow-up, 11 (3.0%) of which were from cardiac causes. Actuarial survival rate was 85.2% at 10 years after surgery. The 10 year-survival rate was similar for patients with single, double, triple vessel disease, and left main trunk disease (94.5%, 83.7%, 75.1% and 89.1%, respectively). For patients with and without old myocardial infarction, the 10 year-survival rate was significantly different (75.4% and 93.3%, respectively) (p less than 0.005). In order to detect which factors of preoperative cardiac function among cardiac index, LV end-diastolic pressure, LV end-diastolic volume index, LV end-systolic volume index, and LV ejection fraction influenced the long-term prognosis, multivariant regression analysis was performed. Only LV end-systolic volume index was a significant factor, and the discriminative point was 50 ml/m2. For patients with LV end-systolic volume index less than 50 ml/m2 and greater than or equal to 50 ml/m2, the 10 year-survival rate was significantly different (88.3% and 32.9%, respectively) (p less than 0.005). In conclusion, the most significant factor influencing longterm prognosis after coronary artery bypass surgery was left ventricular end-systolic volume, indicating the importance of preventing preoperative dilatation of left ventricle. PMID- 1593157 TI - [A retrospective group study on post-thymectomy myasthenia gravis]. AB - Retrospective group study on post-thymectomy myasthenia gravis (post-Tm MG) was carried out. Five hundred and twenty-seven resected thymoma cases (133 cases with MG and 394 cases without MG) were collected from 9 hospitals. Post-Tmx MG occurred in 18 out of 394 cases -4.6% of thymoma without MG-, and these 18 patients with post-Tmx MG were investigated retrospectively. As to surgical procedures, the mode of operation, either thymectomy or thymo-thymectomy was not thought to be an important factor in the pathogenesis of post-Tmx MG. These 18 patients could be divided into 7 with early onset and 11 with late onset. In the early onset group, post-Tmx MG occurred within 6 months after the operation, and these 7 patients may have had subclinical MG at the time of the initial operation. In the late onset group, post-Tmx MG was noted in 5 patients when recurrence of the tumor was confirmed, the latest being 11 years after operation. The pathogenesis of post-Tmx MG could not be clarified in the other 6 patients (33.3%). For further evaluation of these 6 cases, a prospective studies with large scale are needed. PMID- 1593158 TI - [Changes in plasma sulfoconjugated catecholamines during perioperative period of cardiac operations--effect of continuous infusion of dopamine]. AB - In order to clarify the physiological significance of sulfate conjugation of catecholamines and the effect of continuous dopamine infusion on the conjugate formation, we measured the plasma levels of free and sulfoconjugated catecholamines during the perioperative period of cardiac operations. The study group consisted of 12 adult patients who underwent cardiac operations. There were 13 study intervals starting from a day before each operation to 72 hours after each operation for the collection of blood specimen. The plasma levels of free and sulfoconjugated catecholamines were measured by radioenzymatic assay. The plasma levels of free dopamine did not show significant change by the induction of anesthesia, but they increased rapidly after the start of dopamine infusion to the level of 7654.9 +/- 731.7 pg/ml. Thereafter, the plasma free dopamine levels remained steady during the 24 hours after operation at 7516.7 pg/ml to 8449.2 pg/ml. On the other hand, the plasma levels of conjugated dopamine increased progressively by dopamine infusion during the 24 hours after operation. The plasma levels of free adrenaline increased significantly to the level of 1049.5 +/- 117.7 pg/ml by dopamine infusion, and lasted with plateau until the 24th hour after operation at the range of 1076.8 pg/ml to 1218.9 pg/ml. Conjugated adrenaline followed a similar pattern to that of conjugated dopamine, with a progressive increase due to the infusion of dopamine. In the case of noradrenaline, free noradrenaline started to increase at the time of cardiopulmonary bypass and showed a further increase by dopamine infusion during the first hour after operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593160 TI - [A study of changes in extravascular lung water after extracorporeal circulation- clinical and experimental studies of decremental factors]. AB - Accumulation of water in the interstitial spaces of the lung disturbs gas exchange, and can progress to pulmonary edema, a critical complication. To assess the prophylactic measures that can be taken to prevent such a pulmonary complication, we have clinically and experimentally investigated the factors that affect extravascular lung water (EVLW), especially, those factors which can be used to decrease the EVLW. Clinically, the relations of the change rate of EVLW (%EVLW) to colloid osmotic pressure (COP), urine out put and water balance were studied in post-operative patients after Extracorporeal circulation. It was found that an increase in COP, and/or an increase in urine out put contributed in lowering the EVLW. A minus water balance also contributed to lower the EVLW. To clarify further the roles of factors in regards to EVLW, an experiment was conducted using dogs. The dogs were intubated and put under controlled mandatory ventilation (CMV) using a respirator. They were divided into the following 4 groups and their EVLW values were measured. Group I; CMV only. Group II; CMV with 10 cmH2O positive end-expiratory pressure (PEEP). Group III; CMV (with 10 cmH2O PEEP) with continuous infusion of normal saline. Group IV; CMV (with 10 cmH2O PEEP) with plasma infusion and drug induced diuresis. In the first 3 groups, EVLW increased in respect to time. In group IV, in which COP was elevated, and a high urine output level and negative water balance was maintained by infusion of plasma and drug induced diuresis, the EVLW did not increase but decrease in respect to time. These experimental results were in accordance to the clinical observations. Therefore, from the clinical and experimental findings, it can be said that vigorous use of diuretics and infusion of plasma decreases the post operative EVLW. This implicated prevention of the accumulation of water in the pulmonary interstitium, preventing pulmonary complications. PMID- 1593159 TI - [Long-term patency of aorto-coronary saphenous vein grafts]. AB - One hundred eighty-two cases with 814 aorto-coronary saphenous vein grafts were studied according to coronary risk factors (smoking, hypertension, hyperlipidemia, diabetes mellitus, obesity and family history). The patency rates of all cases were as follows, early-term (within one year after operation): 92.3%, mid-term (within 5 years after operation) 80.7%, long-term (more than 5 years after operation): 66.0%. Coronary risk factors have great influence upon the mid- and long-term patency, especially upon the latter. The long-term patency rate of the grafts complicated with hyperlipidemia was 57.4% and that without hyperlipidemia was 81.8% (p less than 0.01). Hyperlipidemia, complicating 55.5% of all cases, was one of the most influential factors on the patency and also the most difficult one to be controlled. In the United States and Europe, many cases were complicated with hyperlipidemia, and it was considered that the poor patency of the saphenous vein grafts in those countries was due to this fact. Pathological studies revealed that hyperplasia of intima and media, characteristics of venosclerosis, appeared frequently in the saphenous vein grafts having more than three risk factors, and that the factors had effect not only upon arteries but also upon veins. So we conclude that saphenous vein grafts are the materials of good long-term patency, and that the control of the risk factors, particularly hyperlipidemia, is the key to improve the patency. PMID- 1593161 TI - [Long-term follow-up of exercise tolerance after coronary bypass grafting]. AB - Six hundred forty-eight serial graded exercise tests were performed on 400 patients up to 10 years after coronary bypass graftings (CABG). The maximal attained exercise tolerance, over 10 METS, were observed in 60% of patients and the negative response to exercise test in 43% of patients. The positive response in various parameters were observed at the following rates: graft occlusion-30% vs graft patent-46% (p less than 0.01); incomplete revascularization-39% vs complete revascularization-22% (p less than 0.01); and less than or equal to 8 METS 4-45% vs greater than or equal to 10 METS-28% (p less than 0.01), respectively. However, no significant difference was observed among number of vessels diseased, number of graftings, and presence of old myocardial infarction. The maximal attained stage of exercise, over 10 METS, in various parameters were at the following rates: less than or equal to 59 years old-70% vs greater than or equal to 60 years old-44% (p less than 0.01); male-63% vs female-32% (p less than 0.01); and graft patent-63% vs graft occlusion-50% (p less than 0.05), respectively. The serial analysis of exercise test demonstrated that improved exercise tolerance appears to persist for at least 5 years after CABG. However, the patients in complete revascularization had a tendency to increase the rate of positive response. In conclusion, the completeness of revascularization as well as graft patency was the main factor limiting exercise tolerance, and correlates with the extent and the duration of improvement after CABG. PMID- 1593162 TI - [Reperfusion injury after heart-lung transplantation--OP41483-alpha-CD (prostaglandin I2 analogue) as a preventive for the reperfusion injury, especially the oxygen derived free radicals]. AB - In clinical heart-lung transplantation, reperfusion injury is a serious problem. This study was undertaken to evaluate the preventive effect of OP 41483-alpha-CD (OP) as a stable prostaglandin I2 analogue on the reperfusion injury, especially oxygen derived free radicals after the heart-lung transplantation. The heart-lung transplantation was performed according to the Schaefers' method. Explanted heart lung block was immersed and preserved in the UW solution for just 4 hours at 4 degrees C. In the OP group, OP was administered to the grafts through the pulmonary artery for 25 minutes before and after the reperfusion. No spin adducts were detected in the plasma before harvest of the graft by ESR spectroscopy. But after the onset of reperfusion, free radical in the plasma could be detected. Those signals were 2.007 of the g factor and 15.5 G of the hyperfine splitting constancy (aN). These findings suggested that the free radical detected in the blood of this model was hydroxyl radical. Max dp/dt, left ventricular pressure and cardiac index were higher in the OP group than in the control group after reperfusion, but there was no difference in the left ventricular end-diastolic pressure between two groups. And adenosine triphosphate contents of the myocardial cell was higher in the OP group than in the control group at 60 min after the onset of reperfusion. Oxygenation by the graft's lung was better in the OP group than in the control group after reperfusion. Radical intensities of the plasma by ESR after reperfusion were significantly higher in the pulmonary vein than in the coronary sinus. When OP was administered, radical intensities in the lung and the plasma of the pulmonary vein were significantly lower in the OP group than in the control group. Thiobarbituric acid-reactive substances increased gradually, in two groups with less increase in the OP group. These show that the free radicals, especially.OH generated from the transplanted heart and lung contribute to the reperfusion injury. The platelet counts in the systemic blood, furthermore, did not change appreciably in the OP group, but decreased rapidly in the control group. Probably the microemboli formation was partially inhibited by the administration of OP. Following the onset reperfusion, the free radicals attack the cell membranes and cause the cell damage. When OP was administered through the pulmonary artery, less free radicals were generated in the lung, and the microemboli were possibly inhibited by platelets anti agglutination. OP administration is useful in the heart-lung transplantation. PMID- 1593163 TI - [Open heart surgery without homologous blood transfusion in small children of body weight less than 20 kg]. AB - In 28 children with congenital cardiac lesions, open heart surgery was attempted without homologous blood transfusion using extreme hemodilution for cardiopulmonary bypass (CPB) and moderate to profound hypothermia. The entry criteria for this study were preoperative hemoglobin value above 10 g/dl and expected CPB time of less than 120 minutes. Acyanotic heart diseases such as ventricular or atrial septal defect were the main lesion, but some cases of tetralogy of Fallot and single ventricle were also included in this study. Intraoperative saving of autologous blood and autotransfusion using cell saver were carried out in a part of the subjects. Acceptable lowest values for hemoglobin was 4-5 g/dl and 40% for mixed venous oxygen saturation. As the results, 18 patients tolerated CPB without transfusion and eventually 16 patients were discharged without transfusion at all. The body weight for those without transfusion was 13.9 kg in average and the lowest was 6.8 kg. The significant factor affecting the needs for homologous blood transfusion was prolonged CPB time over 120 minutes. Although there was a tendency that the patients with body weight less than 15 kg received transfusion more frequently than those with body weight more than 15 kg, the body weight was not necessarily a limiting factor. Pre-CPB blood saving and intraoperative autotransfusion were the positive factors for successful non-transfusion open heart surgery. PMID- 1593164 TI - [Analysis of the malignant potentiality in superficial esophageal carcinoma by cytofluorometry of nuclear DNA and cellular protein contents--in relation to histopathologic findings and prognosis]. AB - Recently patients with superficial esophageal carcinoma have increased due to progress in endoscopy, but the results of surgical treatment are still not satisfactory. Cytofluorometric analysis of nuclear DNA and cellular protein contents, measurements of malignant potentiality, in superficial esophageal carcinoma were performed, and DNA ploidy patterns were compared statistically with histological findings and prognosis. Nuclear DNA and cellular protein contents were measured by the multiparametric cytofluorometry in 72 patients with squamous cell carcinoma (mucosal ca.: 14 cases, submucosal ca.: 58 cases). DNA ploidy patterns were classified into diploid (without polyploid), polyploid, and aneuploid according to the peaks of the DNA content histogram. In the current study, there were 22 cases (30%) of diploid, 17 cases (24%) of polyploid, and 33 cases (46%) of aneuploid. In patients with polyploid and aneuploid, there was high frequency of lymph vessel invasion, as compared with diploid (p less than 0.01). The overall five-year survival rates of patients with diploid, polyploid, aneuploid were 91%, 71%, 55%. The prognosis in patients with aneuploid was poorer than diploid (p less than 0.05). The recurrent cases of early esophageal carcinoma were aneuploid only. DNA ploidy patterns proved to be one of the major prognostic factors by multivariate analysis. The patients with higher DNA content had a high frequency of lymph node metastasis. In the patients with poor prognosis, cellular protein content showed higher. These results suggest that the analysis of nuclear DNA and cellular protein contents are useful for assessing the prognosis and planning postoperative combined therapy in patients with superficial esophageal carcinoma. PMID- 1593165 TI - [Emergency coronary artery bypass grafting for failed percutaneous transluminal coronary angioplasty]. AB - There were 1151 patients who underwent PTCA at our facilities from August 1984 to December 1990. The records of 298 patients were reviewed from August 1984 to June 1988 (former period), and were compared with records of 853 patients undergoing treatment after June 1988 (latter period). Of 852 elective PTCA procedures, complete occlusion of the lesion increased from 2.3% in the former period to 17.5% in the latter period, while for partial occlusion there were 60.4% in the former and 60.5% in the latter. Emergency PTCA for acute myocardial infarction decreased from 37.2% in the former to 22% in the latter. The number of patients with multivessel disease increased slightly from 43.6% in the former to 46.8% in the latter. The success rate for patients who underwent elective PTCA for complete occlusion was 42.8% in the former and 49.6% in the latter, while for partial occlusion it was 87.2% in the former and 91.8% in the latter. The success rate for patients requiring emergency PTCA was 73.8% in the former and 90.4% in the latter. Of the patients undergoing elective PTCA, acute coronary closure occurred in 3% of the former and in 1% of the latter, while for patients requiring emergency PTCA, there were 4.4% in the former and 2.7% in the latter. Of the 8 patients who required emergency CABG, elective PTCA was unsuccessful in 4 cases and emergency PTCA was also unsuccessful in the other 4; in other words, 4 of a total 852 elective PTCAs (0.47%) and 4 of 299 emergency PTCAs (1.3%) for an overall figure of 8/1151 (0.7%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593166 TI - [Successful post-left ventricular aneurysmectomy left ventricular assist with a centrifugal pump]. AB - A 71-year-old male with a left ventricular aneurysm underwent aneurysmectomy. The patient could be weaned from cardiopulmonary bypass with high-doses of dopamine and dobutamine, followed by immediate left ventricular failure and systemic hypotension. IABP could not be applied to the patient because of the kinked bilateral common iliac arteries. In this condition a centrifugal pump system was connected between left atrium and ascending aorta. With a pump flow of 2 L/min the patient returned to an intensive care unit. After 48 hours of left heart bypass with minimal anticoagulation with systemic heparinization the device could be removed. The patient recovered without any complications, such as thromboembolism, renal failure or mediastinitis. He discharged in fair condition 3 months after the operation. PMID- 1593167 TI - [Experience in the treatment of acute fulminating myasthenia gravis]. AB - During past 15 years, 188 myasthenia gravis (MG) patients underwent thymomectomy or thymectomy with extended resection of the adipose tissue around the thymus in our institution. Four of 188 patients (2%) had to be given respiratory support within 2 months after the onset of MG. We defined this MG as the acute fulminating type. There were 2 male and 2 female patients, ranging in age from 22 to 44 years (average, 32.5 years). Three of these patients had thymoma. One of these patients was post-thymomectomy myasthenia gravis and another patient was d penicillamine induced myasthenia gravis. Two patients admitted on respirator for respiratory crisis. All patients underwent operation within 2 weeks after admission. The duration of respiratory support ranged from 10 to 120 days (mean 44) after operation. The period of the hospital stay ranged from 8 months to 2 years 1 month (mean 1 year 5 months). During acute stage after operation, the patients needed ACTH, steroid, immunosuppressants (azathioprine, Bredinin) and plasma pheresis depending on their severity of myasthenic symptoms. In 2 patients dose of steroid could be reduced without deterioration of the symptoms. They are doing well with small dose of steroid. In one patient plasma pheresis was performed 6 years after thymectomy. Various symptoms due to myasthenia gravis and rheumatoid arthritis has recurred 10 years after thymectomy. The titer of acetylcholine receptor antibody of this patient has been continuing in high level. PMID- 1593168 TI - [Intrapericardial lipoma with stenosis of the left bronchus and pulmonary artery]. AB - In a 1-year-6 month-old girl with asthma, a chest magnetic resonance imaging revealed an intrapericardial lipoma at the site of the transverse sinus behind the great arteries. The tumor compressed the left bronchus and pulmonary artery resulting in the stenosis. Under cardiopulmonary bypass, the tumor was successfully removed. The stenosis of the left bronchus and pulmonary artery were released. PMID- 1593169 TI - [Dissecting aortic aneurysm involving an aberrant right subclavian artery]. AB - A 51-year-old man was admitted with severe interscapular and chest pain. Chest X ray showed marked widening of the mediastinum. Aortography demonstrated DeBakey IIIb type dissecting aortic aneurysm and an aberrant right subclavian artery arising from the diverticulum of Kommerell. The intimal tear was repaired with direct suture closure with the aid of femoro-femoral bypass. Although the dissecting lumen was not obliterated completely, the patient has been well for seven years on antihypertensive treatment. This is a rare combination of congenital and acquired disease of the aorta. As far as we know, this is the first report in Japanese literature. PMID- 1593170 TI - [Autologous blood transfusion with erythropoietin in heart surgery in an anemic patient]. AB - A 78-year-old woman was diagnosed as having three-vessel coronary artery disease. A coronary artery bypass operation with autologous blood transfusion was indicated because of the irregular antibody and because homologous blood transfusion would lead to hemolytic complications. Since she had anemia (hemoglobin level, 10.7 g/dl) and autologous blood could not be collected, recombinant human erythropoietin (rHuEPO) and iron preparations were administered intravenously every day. The hemoglobin level reached 12.1 g/dl two weeks after administration, and then autologous blood was donated. The first 1200 ml of blood was stored frozen, and the last 400 ml as liquid in consideration of the blood preservation period. Surgery was performed uneventfully after 8 weeks of rHuEPO administration. No homologous blood transfusion was required during and after surgery. By using rHuEPO, it is thus possible to perform heart surgery without homologous blood transfusion even in patients with anemia, for whom blood transfusions have been considered necessary. PMID- 1593171 TI - [Two cases of Marfan syndrome, surgically treated for complicating spontaneous pneumothorax]. AB - Two cases of spontaneous pneumothorax in the patients of Marfan Syndrome were reported. Nine and 13-year-old girls were admitted to our hospital complaining of chest pain and dyspnea for the first time. Tension pneumothorax was confirmed by the chest radiograph. Both of them had the physical stigmata of Marfan Syndrome including cardiovascular abnormalities. The drainage tube was inserted into the thoracic cavity. As the drainage was ineffective, the surgical treatment was undertaken. The thoracic cavity was opened though axillary incision and bullae were resected. The patient of pneumothorax with the Marfan Syndrome should be examined preoperatively about cardiovascular abnormality using chest computed tomography and echocardiography. As far as the surgical intervention was concerned, the axillary approach is preferred to the median sternotomy, as such patient highly probably require cardiovascular operation in future. PMID- 1593173 TI - [Methicillin-resistant Staphylococcus aureus endocarditis following patch closure of ventricular septal defect]. AB - Mediastinitis due to methicillin-resistant Staphylococcus aureus was found on the ninth postoperative day after patch closure of ventricular septal defect (VSD) in a six-month-old girl. Intravenous administration of vancomycin and debridement of the wound followed by irrigation with povidone iodine and vancomycin led to wound disinfection, but blood cultures continued positive. On the 22nd postoperative day, an echocardiographic examination revealed vegetations in the right ventricle. An emergency open heart operation was undergone. The largest vegetation was 1 x 2 cm in size, originating from the intracardiac patch used for closure of the VSD. The pulmonary and tricuspid valves were also involved. After removal of the infected tissues, including the two cusps of the pulmonary valve and a part of the tricuspid valve, the ventricular septal defect was closed again with a woven Dacron patch. The defect in the tricuspid valve was repaired. Postoperative examinations revealed severe pulmonary regurgitation and mild tricuspid regurgitation, but the cardiac function was good and neither vegetation nor leakage around the patch was recognized. PMID- 1593172 TI - [MRSA pyothorax due to bronchopleural fistula after grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta--a successful treatment by open drainage and omentopexy]. AB - Treatment of postpneumonectomy pyothorax due to bronchopleural fistula (BPF) is troublesome, especially with methicillin-resistant staphylococcus aureus (MRSA) infection. Moreover, in a bypass-grafting case, the management becomes more complicated. We reported a successful treated case of MRSA pyothorax due to BPF after grafting and pneumonectomy. In a 48-year-old woman performed grafting and pneumonectomy for traumatic aneurysm of the thoracic aorta, MRSA pyothorax due to BPF occurred. BPF was successfully closed by fibrin-glueing under bronchofiberscopy. However pyothorax was not improved by thoracic irrigation for a month. Therefore, open pleural drainage underwent. At the same time, bronchial stump and graft surface was covered with the omental pedicle flap. The open wound had become sterile in two months, and the thoracic window was closed three months after the open drainage. PMID- 1593174 TI - [Application of an expandable metallic Z-type stent for stenosis of the left main bronchus following tuberculosis--a case report]. AB - A 32-year-old man had been suffering from dyspnea on exertion and stridor, which were due to stenosis of the left main bronchus as a complication of bronchial tuberculosis. A three-connection stent, 1.2 cm in diameter and 4.5 cm in length was placed at the site of the bronchial stenosis. Dyspnea disappeared 2 days after the procedure, and the pulmonary function 3 weeks later showed considerable improvements in %FVC, FEV1 and MMF. PMID- 1593175 TI - [A successful case of tricuspid valvulectomy for Ebstein's anomaly with severe tricuspid stenosis]. AB - A 44-year-old male was admitted to our hospital complaining of general fatigue and dyspnea on exertion with congestive heart failure (NYHA IV). Cardiac catheterization and angiogram revealed Ebstein's anomaly with severe tricuspid stenosis and functioning small right ventricle. Because of tiny right ventricular chamber, the usual surgical treatment for Ebstein's anomaly i.e. tricuspid valve replacement or valvuloplasty were deemed to be inappropriate. Tricuspid valvulectomy was performed to relieve the inflow stenosis of the right ventricle and excellent symptomatic relief was achieved. It is very rare to seen an adult case of Ebstein's anomaly with severe tricuspid stenosis and functioning small right ventricle. Tricuspid valvulectomy may be justified to use in this rare condition. PMID- 1593176 TI - [Intra-atrial implantation of mitral valve prosthesis in 2 patients with active infective endocarditis complicated by mitral annular destruction]. AB - This is a report of two patients with extensive destruction of the mitral annulus due to active infective endocarditis. Patient 1 was a 66-year-old female and the patient 2 was a 59-year-old male. In both patients medical therapy had failed to control endocarditis and emergency mitral valve replacements were carried out. At the operation special surgical techniques were necessitated, since insertion of artificial valves in the annulus was impossible because of the lack of the annular tissue due to destruction and excision. On the posterior commissure side, mitral valve prosthesis were sutured to the left atrial wall just above the anatomical mitral ring. Furthermore, in patient 2, a bovine pericardium collar attached to the prosthetic valve was sutured to the left atrial wall to secure fixation of the prosthetic valve. The postoperative courses were uneventful in both patients. This technique seems to be useful in patients with mitral annular destruction. PMID- 1593177 TI - [A case of intrathoracic chest wall type lipoma]. AB - Intrathoracic lipoma is a comparatively rare disease. We have recently experienced a case of intrathoracic chest wall type lipoma associated with Charcot-Marie-Tooth disease. The case was a 16-year-old man, in whom preoperative examination of his foot-drop due to Charcot-Marie-Tooth disease pointed out an abnormal chest shadow. Image diagnosis led to intrathoracic chest wall type lipoma. The tumor was easily resectable and was lipoma pathohistologically as well. The literature presented us with 22 cases of such lipoma, which appeared to be predominant for age not more than 10 and age 41-60 and to occur favorably in postero-superior chest wall. Preoperative diagnosis of the present disease became possible to a certain extent by means of CT, MRI. However, in view of imperfect differentiation between lipoma and liposarcoma, surgical resection should be considered, if possibly. No case of intrathoracic lipoma associated with Charcot Marie-Tooth disease had been reported in the literature, and the causal relationship there between also remains unknown, but to be further examined. PMID- 1593178 TI - [Preoperative diagnosis of a thoracic duct cyst arising in the supraclavicular fossa--surgical case report]. AB - The incidence of cysts of the thoracic duct is very low, and they are reported to account for only 0.0005-0.5% of all mediastinal tumors. As far as we have been able to determine, there have been no more than 24 case reports of the surgical resection of such cysts, including our own. Moreover, lesions of the left supraclavicular fossa as in the present case were noted in only 2 reports from Western countries, and 2 cases can be found in the Japanese literature. We encountered a case of thoracic duct cyst where we were able to make a diagnosis preoperatively by means of needle aspiration, and report it here together with a discussion of the relevant literature. The patient was a 64-year-old woman who was admitted with the chief complaint of pain in the throat and a sense of pressure in the neck. A swelling was noted in the patient's left supraclavicular fossa, and when this was aspirated it yielded approximately 15 cc of yellowish white, chylous fluid. No hoarseness or dysphagia were noted. CT scan of the thorax revealed a smooth-surfaced tumor extending from the left supraclavicular fossa to the anterior mediastinum. It showed the simple cystic lesion. On the basis of these findings, a diagnosis of thoracic duct cyst arising in the left supraclavicular space was made. Following excision, the patient's postoperative course was favorable. PMID- 1593179 TI - [Left atrial myxoma with production of interleukin 6]. AB - A surgically treated case of left atrial myxoma is reported. A 66-year-old man with a history of cough and orthpnea had an echocardiographic and an MRI diagnosis of left atrial myxoma. He had the constitutional signs of myxoma including acceleration of E.S.R., positive CRP, hyperimmunoglobulinemia, loss of body weight, and so on, in addition to the symptoms of heart failure. Cardiac surgery was performed on him under extracorporeal circulation on June 12, 1990. A large myxoma with a diameter of 6.0 cm x 4.8 cm that was adhering to the fossa ovalis with a stalk was resected. Afterwards the symptoms of both heart failure and the constitutional signs disappeared, and the postoperative course was uneventful. Studies of the excised specimen demonstrated that this tumor produced Interleukin (IL-6). After operation the level of the serum IL-6 that was high before operation was normalized. This suggests that the symptoms and the laboratory results pointing to an autoimmune disease were due to the IL-6 produced from the cardiac myxoma. This is the first report that the localization of the IL-6 in the left atrial myxoma is demonstrated with immunohistochemical stain. PMID- 1593180 TI - [Total correction of truncus arteriosus with severe truncal valve insufficiency in neonate]. AB - The prognosis of infants with truncus arteriosus associated with severe truncal valve insufficiency is quite poor. Total correction was successfully performed in a neonate with such a complicated anomaly. The patient was 21 days old female with anuria due to severe congestive heart failure preoperatively in spite of medical treatment. She underwent Rastelli operation and pulmonary artery was reconstructed using autologous pericardial 3 valved conduit. Truncal valve was 4 cusps with the malformed nodular margins and one cusp had cleft. This cleft was closed suturing the cleft cusp and adjacent cusp each other and annuloplasty was added in 4 commissures. She survived and her truncal valve insufficiency was still mild at 2 years post-operative period. Although total correction with truncal valve repair for such a severely ill neonate and young infant with truncus arteriosus as this patient has not been reported, our experience suggests that severe truncal valve insufficiency could be fairly well repaired by valvulo annuloplasty. PMID- 1593181 TI - [Microbial carbon-phosphorus bond degrading enzymes]. PMID- 1593182 TI - [The role of cell cycle control genes (the retinoblastoma susceptibility gene and cdc2 gene) in proliferation and differentiation of hematopoietic cells]. PMID- 1593183 TI - [Capillary electrophoresis: separation principle and application]. PMID- 1593184 TI - [Maple syrup urine disease: molecular pathology of the branched chain alpha-keto acid dehydrogenase complex]. PMID- 1593185 TI - [Lipophorin in insects]. PMID- 1593186 TI - [Functions of carbohydrates attached to erythropoietin]. PMID- 1593187 TI - [K+ channels: their function and structure in NG-108-15 neuroblastoma cells]. PMID- 1593188 TI - [Defense mechanisms of marine invertebrates]. PMID- 1593189 TI - [Eukaryotic replication fork: three DNA polymerases on two DNA strands]. PMID- 1593190 TI - [Functional regulation of cytoskeleton by phosphorylation: actin phosphorylation]. PMID- 1593191 TI - [The application of super absorbent polymer to Southern blot technique]. PMID- 1593192 TI - Valgus-flexion osteotomy for middle-aged patients with advanced osteoarthritis of the hip: a clinical and radiological evaluation. AB - We followed up 34 secondary osteoarthritis patients with 38 hips treated by valgus-flexion osteotomy between 1979 and 1985. The average age of the patients at surgery was 45 years and the follow-up period ranged from 5 to 11 years. After surgery, the clinical evaluations were made according to the JOA Hip Score which remained unchanged in all 38 hips for 5 years. After 6 years there were some hips whose score declined with time. It was found that the preoperative extension flexion range was the factor that was most closely associated with the result of the surgery (p less than 0.01). Radiological examination at 5 years revealed that the joint space had been widely broadened and the trabecular structure nearly normalized in 23 hips (60.5%), while 15 hips (39.5%) showed a slight degree of joint space broadening and were left with sclerosis and pseudocysts. After a lapse of 10 years or more, in 13 hips out of 10 patients, seven were found to have osteoarthritic changes and revision had to be done by THR in 2 patients. Valgus-flexion osteotomy can therefore be said to provide one of the useful means to preserve joints when employed in middle-aged patients with secondary OA. PMID- 1593193 TI - [Development of three-dimensional imaging of the musculoskeletal system and its diagnostic capability]. AB - Since 1987 we have studied osseous surfaces reconstructed three-dimensionally (3 D) from CT images with the cooperation from Hitachi Medico Co., Ltd. From these studies we have developed the following method for various clinical use. The method of this 3-DCT system could treat rather noisy images scanned with low radiation exposure because of the high contrast ratio (CT number) between bones and soft tissues, in the CT images. In addition, the 3-D calculation treated only the extracted data instead of all the CT images data, and the high speed processor was used in our system. These were effective to reduce the processing time. Furthermore, the system provided a natural stereoscopic view using a mixture shading method. Subsequently, this 3-DCT system was applied to clinical cases to examine its diagnostic capability. These results indicate that the 3-DCT system is useful in evaluating pathological conditions of bones and joints. PMID- 1593194 TI - Lateral elbow pain syndrome and entrapment of the radial nerve. AB - Lateral elbow pain syndrome is probably a fairly common condition and known to be resistant to conservative treatments. It is suggested that this syndrome is caused by entrapment of the radial nerve. Thirty patients with lateral elbow pain syndrome, in which entrapment of the radial nerve was diagnosed, have been operated upon to release the radial nerve at the elbow. There were 9 men and 21 women. Their age ranged from 17 to 64 with an average of 42.5. Twenty one of thirty nerves were entraped by the arcade of Frohse or other soft tissues. Nine nerves were adherent to the tissues overlying the radial head. Follow-up has been from six months to two years and eight months. Postoperative results were excellent in 16 patients, good in 11, fair in two and poor in one. These results would indicate that entrapment of the radial nerve at the elbow is considered as a cause of lateral elbow pain syndrome. PMID- 1593195 TI - [Anatomical study of the normal and degenerative articular surfaces on the first carpometacarpal joint]. AB - Specimens of 138 first carpometacarpal joints (CMJ) from cadavers consisting of 59 females and 79 males and averaging 68.8 years of age were grossly evaluated and morphological measurements were performed. Macroscopic degeneration of cartilage surface was noted in the metacarpus of 97 hands and trapezium of 73 hands. 1) Morphological measurements of normal articular surfaces showed that metacarpal concave depth was shallower in the female than in the male and trapezial convex height was flatter in the female than in the male. 2) The degeneration of the articular surface was more often observed in the metacarpal joint than the trapezial joint, and the degree of degenerative changes on each articular surface was greater in the female than in the male. 3) In Grade I, the degeneration of the cartilage surface was observed both in the radial and ulnar facets of the trapezium and in the dorsal and palmar facets of the metacarpus. 4) As the degeneration progressed in both sexes, the trapezial concavity became deeper and its convexity became flatter than normal. On the other hand, the metacarpal concavity was flatter and its convexity was higher than normal. Moreover, these changes were more apparent in the female than in the male. PMID- 1593196 TI - [Stress analysis of femoral stems in cementless total hip arthroplasty by two dimensional finite element method using boundary friction layer]. AB - To develop stem design achieving primary fixation of stems and effective load transfer to the femur, we studied stress analysis of stems in cementless total hip arthroplasty by two-dimensional finite element method using boundary friction layer in stem-bone interface. The results of analyses of stem-bone interface stresses and von Mises stresses at the cortical bones indicated that ideal stem design features would be as follows: 1) Sufficient length, with the distal end extending beyond the isthmus region. 2) Maximum possible width, to contact the cortical bones in the isthmus region. 3) No collars but a lateral shoulder at the proximal portion. 4) A distal tip, to contact the cortical bones at the distal portion. PMID- 1593197 TI - [Influence of an interlocking condition on the fracture healing process]. AB - In order to clarify the influence of interlocking condition on the fracture healing process, the following three studies were carried out. First, an axial loading test was done in which an interlocking nail was inserted into a osteotomised human femoral bone. As a callus substitute, several kinds of resin were packed into the osteotomy gap. Load-formation curves were detected with strain gauges. These experiments suggest that the strain of the fractured end and its substitutes increase as the stiffness of the substitutes increases. Next, three weeks after the fixation with an interlocking nail of the osteotomized rabbit femur, the half of the femora were dynamized. The other half were not. Four to 56 weeks after osteotomy, the femora were harvested for radiographical and histological examination. No significant differences were detected between the two groups. In the last study, static and dynamic condition models similar to the second experiment were made. At 12 weeks, femora were harvested and measured for maximum bending strength. There were no statistically significant differences. These studies suggest that a so-called static condition has no unfavorable effects on fracture healing. PMID- 1593198 TI - [Development of ligament-bone junction in anterior cruciate ligament reconstruction with the scaffold type polyester artificial ligament (Leeds-Keio) in the dog]. AB - The anterior cruciate ligament (ACL) was reconstructed in sixty mongrel dogs with artificial ligament (Leeds-Keio). The tibial ligament-bone junction was completely removed before the reconstruction in order to investigate the remodelling process of the junction. The dogs were divided into five groups. In all of these the artificial ligament was taut when implanted except for one group which had deliberately a slack reconstruction. In three groups the reconstructions included the use of a strip of infrapatellar synovium alone or with a strip of fascia lata within or outside the artificial ligament. After two, four, twelve and twenty-four weeks, the tibial junction was investigated macroscopically, histologically and by means of microangiography. Newly formed fibrocartilage and functionally aligned collagen were observed in the junction 12 weeks after the initial surgery in all groups, but not in the group with a slack reconstruction. From the results of this study, it was concluded that infrapatellar synovial transfer improved tissue induction in the early stages, and further, the additional use of the fascia speeded up the remodelling process. PMID- 1593199 TI - [The effect of anesthetic agents on descending spinal cord evoked potential and the compound muscle action potentials elicited by stimulation at the cerebral motor cortex and the spinal cord]. AB - Recently, intraoperative monitoring of the motor tract by descending spinal cord motor evoked potentials (MEP) and compound muscle action potentials (CMAP) has been applied in clinical testing. Since several reports have mentioned the vulnerability of these potentials to anesthetic agents, experimental studies were carried out on the relationship between these potentials and anesthesia using 41 adult cats. The effects of anesthesia on changes in amplitude of the direct wave (D wave) and indirect wave (I wave) of the MEP and CMAPs were investigated. These potentials were generated by stimulation of the spinal cord and the motor cortex, respectively. Enflurane (2%), halothane (1%) and isoflurane (1.5%) with pure oxygen decreased the amplitude of the I wave to less than 50% of the control level. The CMAP after stimulation of the spinal cord was degraded to less than 30%, and the CMAP after cortical stimulation vanished completely. Only the D wave was stable against inhalational anesthetic agents. Sixty-seven percent nitrous oxide with the above concentrations of these inhalational anesthetic agents decreased the amplitude of the I wave to less than 30% and the CMAP evoked by spinal cord stimulation vanished. The effect of modified NLA (diazepam and pentazocine) on these potentials was weaker than that of the inhalational anesthetic agents. PMID- 1593200 TI - [An experimental study on the wear of HDP socket in total hip arthroplasty- quantification of worn surface by SEM 3-D image analysis and effect of gamma-ray irradiation of HDP on improving tolerance to wear]. AB - In order to evaluate the usefulness of gamma-ray-irradiation to improve the tolerance to wear of the sockets, the worn surface of the 2.5 M rad gamma-ray irradiated HDP sockets after total hip arthroplasty has been quantified by a newly-developed 3 dimensional (3-D) image analysis method in combination with scanning electron microscopy (SEM). The SEM 3-D image analysis revealed marked deformation, consisting of unevenness with about a 20-micron difference in height, of the worn surface of the ordinary HDP socket, while the same analysis revealed a smooth surface in the gamma-ray-irradiated HDP socket. The decrease in thickness of the gamma-ray-irradiated HDP socket was about 1/4 that of the ordinary HDP socket. These results indicate that SEM 3-D image analysis is capable of quantifying the morphology of the worn surface and that gamma-ray irradiation improves the tolerance to wear of the socket, thus making its surface resistant to deformation. PMID- 1593201 TI - [Biomechanical analysis of lumbar spinal instrumentations]. AB - Five different types of spinal instrumentation (Steffee, Luque, Zielke, A-O anterior screw and wiring, and A-O anterior and posterior screw and wiring) were tested for biomechanical performance (i.e., relative initial stiffness, the loosening generated in the bone-implant interface during cyclic loading, and the influence on bone calcium content on the first two) using porcine vertebrae. Steffee's instrumentation produced the stiffest construction, followed by A-O anterior and posterior screw and wiring. A positive correlation was noted between the initial stiffness and bone calcium content. With low calcium, cyclic loading caused early loosening in the Steffee's instrumentation while the A-O anterior and posterior screw and wiring maintained its stability. It was concluded that the stability of these instrumentations was dependent on the calcium content and for sustained stability, when the calcium was low, the A-O anterior and posterior screw and wiring was superior to Steffee's. PMID- 1593202 TI - [Experimental studies on vascularized allogeneic joint transplantation in rats]. AB - Examination was made on the effects of Cyclosporine A, an immunosuppressive drug, on vascularized joint allografts. Genetically inbred DA and Lewis rats were used and a model of knee joint orthotopical transplantation across the major histocompatibility barrier was developed. Nine non-immunosuppressive allografts failed to acquire bony union. Twenty-seven short term immunosuppressive rats acquired solid union, but following withdrawal of immunosuppression, the grafts were soon rejected and joint function was lost due to pathological fractures of the grafted bone or joint instability. Thirteen allografts of continuous immunosuppression at a dose of 5 mg/kg/day showed no rejection, though the bone marrow did, and there was no impairment of function. The continuous administration of low and non-toxic dose of Cyclosporine A was necessary for maintaining grafted joint functions. PMID- 1593203 TI - [Experimental study of intrinsic healing of the flexor tendon: collagen synthesis of the cultured flexor tendon cells of the canine]. AB - The roles of the tendon cells, such as epitenon cells and tenocytes, through the reparative process of the flexor tendon are controversial. This study was performed to investigate the collagen synthesis of cultured tendon cells derived from the sheathed flexor tendons of the canine under electron microscopy using "Floating Sheet" method introduced by Arnold, J. R., et al (1983). Morphologically epitenon cells gave an appearance of large and oval fibroblasts, while tenocytes were small, spindle shaped fibroblasts. Electron microscopy revealed large amount of collagen and non-collagen fibers in the intercellular spaces of both cell populations. The collagen fibers produced by tenocyte populations were 200 A to 400 A in thickness, whereas those of the cultured epitenon cells ranged from 150 A to 300 A. These results indicated that tenocytes secreted larger and more matured collagen fibers than epitenon cells. Promotion of collagen synthesis by the tenocytes in the early stage of the flexor tendon repair was thought to be more favorable for its quality of the healing process. PMID- 1593204 TI - [An experimental study on the effect of laminin in vivo on promoting regeneration of axons]. AB - Laminin has been shown to exert a stimulatory effect on neurite outgrowth in vitro, but this biological activity in vivo has not been clarified. The objective of this study was to examine the hypothesis that laminin can stimulate axonal regeneration in vivo. Intubation repair of the rat sciatic nerve was used as a model and the possibility that the maximum distance that axons can regenerate through a tubular nerve guide might be increased by the addition of laminin to the inside of the nerve guide was investigated. Most of the rats with the laminin treated nerve guide displayed excellent axonal bridges across the 12-mm and 20-mm nerve gaps, while none of the rats with an untreated nerve guide had a developed bridge. Histological and electrophysiological findings supported successful long term results. These findings suggest that laminin significantly hastens axonal regeneration in vivo. PMID- 1593205 TI - [Foot deformities from the point of view of biomechanics]. PMID- 1593206 TI - Vitamin A and liver fibrosis: cure or villain? PMID- 1593207 TI - Mutations in protein C: molecular pathology of thrombosis. PMID- 1593208 TI - Aspirin: how does it prevent thrombosis? PMID- 1593209 TI - Free radicals, antioxidants, and human disease: where are we now? PMID- 1593210 TI - The renal sodium-calcium exchanger. AB - The functional expression of the renal sodium-calcium exchanger has been amply documented in studies on renal cortical basolateral membranes. In perfused renal tubules, other investigators have shown sodium-calcium exchange activity in the proximal convolution of the rat and in the distal convolution, the connecting tubule, and the collecting tubule of the rabbit. In rat proximal tubules, we found that the sodium-calcium exchanger is an important determinant of cytosolic calcium homeostasis, since inhibition of sodium-dependent calcium efflux mode caused a large accumulation of tubular calcium. In membranes from rat proximal tubules sodium-calcium activity was high, and in intact proximal tubules, the tubular sodium-calcium exchanger exhibited a high affinity for cytosolic calcium and had a substantial transport capacity, which may be absolute requirements for the maintenance of stable cytosolic calcium in proximal tubules. PMID- 1593211 TI - Regulation of cytosolic free calcium concentration in the rabbit connecting tubule: a calcium-absorbing renal epithelium. PMID- 1593212 TI - Signal transduction and cytosolic calcium changes induced by kinins in renal cells. PMID- 1593213 TI - Interactions of pHi and Ca2+i in vascular smooth muscle tissue. PMID- 1593214 TI - Effects of vitamin A administration on collagen and sulfated glycosaminoglycans contents in the livers of rats treated with carbon tetrachloride. AB - We have investigated the effects of nontoxic doses of vitamin A on the hepatic contents of collagen and sulfated glycosaminoglycans (SGAGs) in rats chronically treated with CCl4. When the animals were treated with this retinoid before the intoxication with CCl4, liver collagen level was significantly reduced as compared with that in rats that received only CCl4 (3.31 +/- 0.40 vs 5.00 +/- 0.61 mg/gm wet liver, mean +/- SD, respectively), although no significant differences were found for the relative proportion of type III collagen related to type I collagen. The absolute increment in the total amount of liver SGAG in the vitamin A--pretreated group was followed by a more important increase in the concentration of dermatan sulfate as compared with the CCl4 group (dermatan sulfate-to-heparan sulfate ratio: 1.15 for the CCl4 group vs 1.70 for the vitamin A--pretreated group). A significant proportion of the dermatan sulfate from this last group was of higher molecular weight when compared with the dermatan sulfate found in the liver of rats that received only CCl4. Our results indicate that the pretreatment with vitamin A modifies hepatic collagen and SGAG deposition and can inhibit or delay the development of liver cirrhosis in rats chronically treated with CCl4. We speculate that this effect could be due to the changes in the fat storing (Ito) cells phenotype induced by vitamin A. PMID- 1593215 TI - Homozygous protein C deficiency: identification of a novel missense mutation that causes impaired secretion of the mutant protein C. AB - We analyzed the promoter region and all the coding exons and exon-intron boundaries of the protein C gene in a Japanese patient with recurrent thromboembolism and complete protein C deficiency. By sequencing these fragments we identified a previously undescribed mutation. A guanine residue was replaced by an adenine residue converting Gly-292 (GGC) to Ser (AGC) in the last exon coding for the catalytic domain. Substitution of this key amino acid, invariably conserved in the serine protease superfamily to which protein C belongs, probably leads to destabilization of the tertiary structure. In a transient expression assay with COS 7 cells, the protein C level was extremely low in the culture medium of the cells transfected with the mutated protein C expression vector, as compared with the normal vector. In contrast, the cell extracts contained similar amounts of mutant and normal protein C, suggesting impaired secretion of the mutant protein C. Using mutagenic primers to introduce a new PvuII site into the mutant allele, we made a study of the family members in this patient's pedigree, revealing that the mutant allele had been inherited in the affected individuals in this pedigree. PMID- 1593216 TI - Allopurinol and dimethyl sulfoxide improve treatment outcomes in smokers with peptic ulcer disease. AB - This prospective, randomized, double-blind study examined whether scavengers of oxygen-derived free radicals are of benefit in the treatment of acute duodenal ulceration in human beings. To this end, allopurinol (50 mg four times a day), a hydroxyl radical scavenger and an inhibitor of xanthine oxidase that forms superoxide radicals, and dimethyl sulfoxide (500 mg four times daily), a hydroxyl radical scavenger, were administered orally with cimetidine. Patients with symptomatic endoscopy-proven acute duodenal ulceration who were smokers and social drinkers were randomized to receive for 8 weeks cimetidine (400 mg two times a day), cimetidine (400 mg two times a day) with dimethyl sulfoxide, or cimetidine (400 mg two times a day) with allopurinol. These patients were then kept on their respective oral regimens (except for those who received cimetidine, for whom the dose was changed to 400 mg at bedtime) for 1 year (maintenance) and followed up for another. After 8 weeks of treatment, the ulceration healed in 69 of the patients (79%) who were given cimetidine alone and in all of the patients who were given dimethyl sulfoxide (n = 85) or allopurinol (n = 84) with cimetidine (p less than 0.01). During the maintenance year, 15 patients (29%), who were given cimetidine nightly, relapsed. Addition of dimethyl sulfoxide or allopurinol to cimetidine was associated with a significantly lower (p less than 0.001) relapse rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593217 TI - Autoimmune neutropenia in Sheboygan County, Wisconsin. AB - Autoimmune neutropenia is thought to be an uncommon disorder in adults. Over a 2 year period, however, autoimmune neutropenia was diagnosed in seven adults in a county with a population of approximately 105,000 people. The median age of the patients was 52 years old (range of 22 to 81 years), and five of the seven patients were women. All seven patients had at least one other symptom of autoimmune disease. Three patients had splenomegaly, three patients had positive direct antiglobulin tests, and two patients had immune thrombocytopenia. Antibodies reacting to neutrophils were detected by either granulocyte agglutination (GA) or granulocyte immunofluorescence (GIF) testing in five of the seven patients. Antibodies in four patients reacted with an 80 kd neutrophil membrane glycoprotein, and antibodies from two people reacted with a 60 kd membrane glycoprotein. Three patients were given treatment with splenectomy, which resulted in only transient improvement in the neutrophil counts. Serious infections occurred in only three patients over the 2 years of observation. In summary, autoimmune neutropenia in adults may occur more often than appreciated. Most cases of autoimmune neutropenia in adults appear to be associated with other autoimmune phenomena. PMID- 1593218 TI - Antibodies to granulocytes in patients infected with human immunodeficiency virus. AB - Individuals who are infected with human immunodeficiency virus (HIV) are known to have a high incidence of autoantibodies. In this study, serum samples from 100 individuals with HIV infection were tested for granulocyte antibodies (red cell antibodies, lymphocytotoxic antibodies, circulating immune complexes, and serum immunoglobulin G levels) by granulocyte agglutination (GA) and granulocyte immunofluorescence (GIF) assays. Granulocyte antibodies were detected in 66% of serum samples by GIF and in 21% of serum samples by GA. None of the positive sera reacted with granulocyte antigens of known specificity. Antibodies that reacted with red cell antigens other than ABO were detected in only three serum samples, but lymphocytotoxic antibodies were detected in 62% of patients. All serum samples were tested by immunoblotting with granulocyte plasma membranes. Only two samples were found to be positive; one sample reacted with a 58 kd protein and one reacted with a 55 kd protein, but neither serum sample immunoprecipitated any protein from granulocytes that were labeled at the cell surface with iodine 125. Since immune complexes that are bound to granulocyte membranes can be detected by GIF, circulating immune complex levels were measured in all 100 samples. Immune complexes were increased in GIF-reactive serum samples compared with GIF nonreactive serum samples (23.3 +/- 19.5 micrograms Eq/ml [mean +/- SD] vs 9.6 +/ 8.1 micrograms Eq/ml, p less than 0.001) but not in GA-reactive serum samples compared with GA-nonreactive sera (24.4 +/- 21.3 micrograms Eq/ml versus 16.9 +/- 16.0 micrograms Eq/ml, p = 0.10).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593219 TI - Bone maturation and resorption by peritoneal macrophages in noninsulin-dependent streptozocin-induced diabetes in the rat. AB - The existence of osteopenia in noninsulin-dependent diabetes mellitus (NIDDM) is controversial. In this regard rats with a diabetic condition that simulates NIDDM have normal bone mineral content. However, normal total mineral content in bones does not preclude abnormalities in more delicate functions in bones of rats with NIDDM (specifically, bone maturation and response of bone matrix to resorptive activity). To evaluate these functions, bone maturation was studied in tibias from 14-week old male and female rats with streptozocin-induced NIDDM and controls. The ability of macrophages to resorb bone was studied in bone particles that were obtained from femors of male rats with NIDDM and controls. The diabetic rats had the overt NIDDM condition for 8 weeks at the time of the study. We found that bone maturation/mineralization remained intact in the diabetic rats and that response of the bone particles that were obtained from their femors to the resorptive activity of macrophages was similar to that of the bone particles that were obtained from controls. These data suggest that in the rat, a diabetic condition that simulates NIDDM does not alter the physiologic functions of the bone matrix. PMID- 1593221 TI - Suppressive effects of pentoxifylline on natural killer cell activity. AB - The methylxanthine derivative pentoxifylline, widely used as a hemorrheologic agent in the treatment of peripheral vascular disease, is now being evaluated for potential applications in patients with cancer. Recent studies have shown that pentoxifylline can modulate a number of neutrophil functions at in vitro concentrations of at least 50 micrograms/ml. Using a standard51chromium-release assay, we studied the suppressive effects of pentoxifylline on natural killer (NK) cell activity and found that pentoxifylline, at concentrations of 50 and 100 micrograms/ml, suppressed the in vitro NK cell activity of healthy volunteers by 25% and 75%, respectively. Postreaction supernatants from chromium-release studies were then assayed for prostaglandin E2 (PGE2) and tumor necrosis factor alpha (TNF-alpha) by using enzyme-linked immunosorbent assay. Concentrations of both PGE2 and TNF-alpha were increased by more than five times in those assay wells containing pentoxifylline. Moreover, the addition of 1 microgram/ml indomethacin to the NK assay system containing pentoxifylline, completely inhibited PGE2 production and abrogated the pentoxifylline-induced NK suppression. The addition of PGE2 (1 x 10(-6) mol/L) to the assay system suppressed NK activity, whereas addition of 1 or 10 ng/ml TNF-alpha did not. Theophylline, another methylxanthine, failed to suppress NK activity like pentoxifylline at equimolar concentrations. Our studies provide the first evidence that concentrations of pentoxifylline of at least 50 micrograms/ml suppressed NK cell function by inducing PGE2 synthesis from effector peripheral blood mononuclear cells. PMID- 1593220 TI - The interactions of penicillamine with copper in vivo and the effect on hepatic metallothionein levels and copper/zinc distribution: the implications for Wilson's disease and arthritis therapy. AB - D-penicillamine does not remove copper from metallothionein, but it has been suggested that it may increase hepatic metallothionein levels. D-penicillamine was shown to increase rat hepatic metallothionein levels; however, the effect was dependent on an interaction with copper. The drug accelerated the excretion of exogenous copper but increased the amount retained on metallothionein. This interaction of penicillamine and copper also provoked changes in the distribution of zinc and in particular an increase in the heat-stable cytosol zinc fraction. In contrast, thiomolybdates were much more effective in eliminating exogenous copper and even removed copper that was already bound to metallothionein; thus, the copper level in the heat-stable cytosol fraction decreased. The observations support the view that patients with Wilson's disease may not be truly "decoppered" but that treatment with d-penicillamine is effective because the accumulated copper in the liver is bound in a nontoxic form by the increased metallothionein. The results explain why cessation of treatment is dangerous. The results may also partially explain the effectiveness of D-penicillamine copper chelates as antiinflammatory drugs. PMID- 1593222 TI - Nonopsonic uptake of Mycobacterium avium complex by human monocytes and alveolar macrophages. AB - The uptake of Mycobacterium avium complex (MAC) microorganisms by human peripheral blood monocytes (PBMs) and alveolar macrophages (AMs) is not well understood. We have previously shown, under opsonic conditions, that humoral factors are important in mediating the uptake of MAC by PBMs. However, the receptor-ligand interactions occurring under nonopsonic conditions remain unclear. We compared the uptake of untreated human PBMs and AMs in a serum-free medium with phagocytes treated to remove surface receptors. Removal of complement receptors CR1 and CR3, the Fc receptor (FcR), and the transferrin receptor (TfR) resulted in significantly lower levels of MAC uptake in serum-free medium by both PBMs and AMs. The addition of barley beta-glucan or mannan from Saccharomyces cerevisiae inhibited MAC uptake by untreated phagocytes in a dose-dependent manner. MAC uptake by PBMs or AMs was never completely abrogated by combining treatments (removal of CR1, CR3, FcR, and TfR and adding mannan or beta-glucan), indicating still-unknown mechanisms of uptake under nonopsonic conditions. We conclude that CR1, CR3, FcR, TfR, the mannose receptor, and possibly a separate beta-glucan-inhibitable receptor all may be involved in nonopsonic uptake of MAC by both PBMs and AMs. PMID- 1593223 TI - Spatial interactions in binocular rivalry. AB - Observers tracked binocular rivalry between a pair of small, foveally viewed gratings whose orientation differed between the 2 eyes. In Experiment 1, a textured annulus surrounding 1 eye's grating increased the total duration of exclusive visibility of the grating only when the grating-annulus separation was less than 0.5 degree. In Experiment 2, observers tracked the visibility of a monocular annulus that surrounded a foveally viewed grating that was either engaged in rivalry or fused with a grating alone viewed by the other eye. The visibility of the annulus was greater when the grating it surrounded was not undergoing rivalry fluctuations. In Experiment 3, the predominance of a rival grating was greater when the contours in the surrounding annulus were orthogonal to those of the rival grating. In Experiment 4, total exclusive visibility of a given grating-annulus target was greater when the grating and the annulus contained the same orientation. PMID- 1593224 TI - Mental rotation, physical rotation, and surface media. AB - Subjects made mirror-normal discriminations on alphanumeric characters shown in different orientations in the picture plane. Either the characters or the background rotated during stimulus presentation in Experiments 1-3. Character rotation in the direction of mental rotation facilitated mental rotation, whereas rotation in the opposite direction inhibited it. In Experiment 4, characters were presented in different surface media so as to stimulate only one representation at a time. Mental rotation performance was similar whether the stimuli were defined by luminance, color, texture, relative motion, or binocular disparity, suggesting that mental rotation occurs at a level beyond that of the independent analyses of these different media. These results support those of Experiments 1-3 in excluding the participation of low-level motion analysis centers in the mental rotation processes. PMID- 1593225 TI - Infants' sensitivity to effects of gravity on visible object motion. AB - A preference method probed infants' perception of object motion on an inclined plane. Infants viewed videotaped events in which a ball rolled downward (or upward) while speeding up (or slowing down). Then infants were tested with events in which the ball moved in the opposite direction with appropriate or inappropriate acceleration. Infants aged 7 months, but not 5 months, looked longer at the test event with inappropriate acceleration, suggesting emerging sensitivity to gravity. A further study tested whether infants appreciate that a stationary object released on an incline moves downward rather than upward; findings again were positive at 7 months and negative at 5 months. A final study provided evidence, nevertheless, that 5-month-old infants discriminate downward from upward motion and relate downward motion in videotaped events to downward motion in live events. Sensitivity to certain effects of gravity appears to develop in infancy. PMID- 1593226 TI - A comparison of infants' and adults' sensitivity to western musical structure. AB - Adults (n = 28) and 8-month-old infants (n = 48) listened to repeated transpositions of a 10-note melody exemplifying the rules of Western tonal music. They were tested for their detection of two types of changes to that melody: (a) a 4-semitone change in 1 note that remained within the key and implied dominant harmony (diatonic change) or (b) a 1-semitone change in the same note that went outside the key (nondiatonic change). Adults easily detected the nondiatonic change but had difficulty with the diatonic change. Infants detected both changes equally well, performing better than adults in some circumstances. These findings imply that there are qualitative differences in infants' and adults' processing of musical information. PMID- 1593227 TI - Evolution of behavioral attractors with learning: nonequilibrium phase transitions. AB - Learning a bimanual coordination task (synchronization to a visually specified phasing relation) was studied as a dynamical process over 5 days of practicing a required phasing pattern. Systematic probes of the attractor layout of the 5 Ss' coordination dynamics (expressed through a collective variable, relative phase) were conducted before, during, and after practice. Depending on the relationship between the initial coordination dynamics (so-called intrinsic dynamics) and the pattern to be learned (termed behavioral information, which acts as an attractor of the coordination dynamics toward the required phasing), qualitative changes in the phase diagram occurred with learning, accompanied by quantitative evidence for loss of stability (phase transitions). Such effects persisted beyond 1 week. The nature of change due to learning (e.g., abrupt vs. gradual) is shown to arise from the cooperative or competitive interplay between behavioral information and the intrinsic dynamics. PMID- 1593228 TI - On the synchrony of stopping motor responses and delaying heartbeats. AB - Recent evidence suggests that inhibition of a motor response may occur as late as the final stages of response execution. Response production involves central commands for autonomic support as well as motoric action. Autonomically controlled responses were used in conjunction with electromyographic and performance indices to examine the timing and flexibility of inhibition. Twenty young male Ss performed a choice reaction time task with stimuli timed according to when they occurred in relation to the R wave of the electrocardiogram. Stop signals, presented on 30% of the trials, induced inhibition. The performance and physiological results generally supported the horse-race model of inhibition. Inhibition was observed as late as during response execution. A short-latency, phasic lengthening of interbeat interval was suggested to reflect the midbrain coordination of the countermanding of response execution. PMID- 1593229 TI - Encoding of text, manual movement planning, and eye-hand coordination during copytyping. AB - Typing span and coordination of word viewing times with word typing times in copytyping were examined. In Experiment 1, typists copied passages of text while their eye movements were measured. Viewing location was determined during each eye fixation and was used to control the amount of usable visual information. Viewing constraints decreased interword saccade size when fewer than 7 character spaces of text were visible to the right of fixation and increased interkeypress times when fewer than 3 character spaces of text were visible. The eye-hand span amounted to 2.8 character spaces. Experiment 2 revealed increases in word typing times and word viewing times as biomechanic typing difficulty increased and word frequency decreased. These findings are consistent with a model of eye-hand coordination that postulates that eye-hand coordination involves central and peripheral processes. PMID- 1593230 TI - Attentional resource demands of visual word recognition in naming and lexical decisions. AB - Attentional demands of lexical access were assessed with dual-task methodology. Subjects performed an auditory probe task alone (single-task) or combined (dual task) with either a lexical decision or a naming task. In Experiment 1, probe performance showed a decrement from single- to dual-task conditions during recognition of words in both lexical decision and naming tasks. In addition, decrements in probe performance were larger during processing of low-frequency compared with high-frequency words in both of the word recognition tasks. Experiment 2 showed that the time course of frequency-sensitive demands was similar across lexical decision and naming tasks and that attention is required early in the word recognition sequence. The results support the assumption that lexical access is both frequency sensitive and attention demanding. PMID- 1593231 TI - Automatic and attentional priming in young and older adults: reevaluation of the two-process model. AB - Three experiments addressed the distinction between automatic and attentional mechanisms underlying semantic priming effects by factorially crossing prime target relatedness, expectancy, and SOA in a task (pronunciation) that minimized postlexical checking processes. Also, possible age-related (young vs. older adults) differences in the automatic and attentional mechanisms were addressed. Across all experiments there was evidence of a Relatedness x Expectancy x SOA interaction, which is inconsistent with the notion of independent automatic and attentional mechanisms in semantic priming and the notion of a self-encapsulated modular lexicon. The results also indicated age-related differences in the build up of the expectancy effect across SOAs when the prime was visually available for only 200 ms, independently of the prime-target SOA (Experiments 1 and 3), but not when the prime was visually available throughout the SOA (Experiment 2). PMID- 1593232 TI - Attentional demands of processing shape in three-dimensional space: evidence from visual search and precuing paradigms. AB - The hypothesis that representation of projective shape is preattentive whereas representation of objective shape in three-dimensional space requires allocation of attention was tested in 2 visual search and 2 precuing experiments. In the visual search experiments, the slope for projective shape search was expected to approach 0 and that for objective shape search was expected to be a positive monotonic function of set size. In the precuing experiments, the effects of precuing were expected to be largely limited to the task requiring representation of objective shape. The overall pattern of results conformed to expectations. The findings are interpreted in the context of a model of shape-at-a-slant processing set out by Epstein and Lovitts (1985) and Epstein and Babler (1989, 1990). PMID- 1593233 TI - Global and local processing in nonattended objects: a failure to induce local processing dominance. AB - Paquet and Merikle (1988) found that subjects can ignore the category of unattended local forms but not that of global forms. Does this finding reflect a priority for global information during perception? In 5 studies, 2 compound stimuli, each surrounded by a frame, were presented side by side, and attention was directed to 1 of the stimuli. The first 2 studies examined whether local dominance would emerge if a small gap (Experiment 1) or the presence of small white lines (Experiment 2) on the surrounding frame specified the target object. No evidence for local dominance was found. Three additional studies examined whether local dominance would be obtained if subjects had extensive practice identifying the local aspect of stimulus displays. Although local practice led to automatic detection of unattended local targets, it did not affect the processing of the global aspect. These results are proposed to exemplify the priority of global information during perception. PMID- 1593234 TI - On the time course of perceptual information that results from a brief visual presentation. AB - A briefly presented visual stimulus engenders an available-information function that lags behind the physical stimulus. We report two experiments that focus on the iconic-decay portion of this function, which falls to 0 over a 200-300 ms period following stimulus offset. In each experiment, to-be-reported digit strings were shown for varying durations followed by a noise mask at varying poststimulus intervals. We found the shape of the performance curve relating digit-report probability to stimulus exposure duration to be independent of stimulus-mask interstimulus interval. This finding is consistent with the proposition that the iconic-decay function's shape is independent of stimulus duration and allows us to identify this shape. We rejected exponential iconic decay for 6 of 8 observers; however, all observers' decay functions could be adequately fit by gamma decay, a generalization of exponential decay. PMID- 1593235 TI - Categorical versus coordinate spatial relations: computational analyses and computer simulations. AB - Results of 4 sets of neural network simulations support the distinction between categorical and coordinate spatial relations representations: (a) Networks that were split so that different hidden units contributed to each type of judgment performed better than unsplit networks; the reverse was observed when they made 2 coordinate judgments. (b) Both computations were more difficult when finer discriminations were required; this result mirrored findings with human Ss. (c) Networks with large, overlapping "receptive fields" performed the coordinate task better than did networks with small, less overlapping receptive fields, but vice versa for the categorical task; this suggests a possible basis for observed cerebral lateralization of the 2 kinds of processing. (d) The previously observed effect of stimulus contrast on this hemispheric asymmetry could reflect contributions of more neuronal input in high-contrast conditions. PMID- 1593236 TI - Beyond the search surface: visual search and attentional engagement. AB - Treisman (1991) described a series of visual search studies testing feature integration theory against an alternative (Duncan & Humphreys, 1989) in which feature and conjunction search are basically similar. Here the latter account is noted to have 2 distinct levels: (a) a summary of search findings in terms of stimulus similarities, and (b) a theory of how visual attention is brought to bear on relevant objects. Working at the 1st level, Treisman found that even when similarities were calibrated and controlled, conjunction search was much harder than feature search. The theory, however, can only really be tested at the 2nd level, because the 1st is an approximation. An account of the findings is developed at the 2nd level, based on the 2 processes of input-template matching and spreading suppression. New data show that, when both of these factors are controlled, feature and conjunction search are equally difficult. Possibilities for unification of the alternative views are considered. PMID- 1593237 TI - Check behind the ears. PMID- 1593238 TI - Niacin reaction. PMID- 1593239 TI - Tobacco logo recognition. PMID- 1593240 TI - Words as therapy: smoking cessation. PMID- 1593241 TI - The Tobacco Institute: helping youth say "yes" to tobacco. PMID- 1593242 TI - The role of the family physician in ending the tobacco pandemic. PMID- 1593243 TI - A controlled trial to integrate smoking cessation advice into primary care practice: Doctors Helping Smokers, Round III. AB - BACKGROUND: Although most physicians believe that smoking cessation assistance is important for their patients, the majority of smokers report that they have not received smoking cessation advice from a physician. We therefore tested whether on-site recruitment, training, and organizational assistance in incorporating a smoking intervention system of documented efficacy into nonvolunteer primary care practices would result in higher rates of smoking cessation advice to patients. METHODS: This was a nonrandomized trial comparing all 10 primary care clinics in an intervention area to all 8 primary care clinics from a geographically separate control area. The evaluation was based on the smoking intervention activities of each of the clinics as reported on preintervention and postintervention mail surveys of cohorts of regular smokers seen in the clinics. RESULTS: Preintervention, 22.9% +/- 11.2% of the intervention clinic cohort and 21.9% +/- 9.6% (P = .84) of the control clinic cohort reported that they had been asked about tobacco during a clinic visit in the prior 6 months. Postintervention, the intervention clinic cohort was significantly more likely to report that someone had asked them if they smoked (39.8% +/- 12.3% vs 26.0% +/- 12.2%; P less than .05), that their physician asked them to quit if they were currently smoking (40.5% +/- 12.1% vs 26.4% +/- 14.6%; P less than .05), and that someone had commended them if they had recently quit smoking (28.2% +/- 19.8 vs 11.3% +/- 11.8%; P less than .05). CONCLUSIONS: The intervention significantly increased the rates at which a population of primary care clinics identified their patients who smoked, advised them to quit smoking, and commended those who had recently quit smoking. PMID- 1593244 TI - Clinical evaluation of the contact sensitization potential of a transdermal nicotine system (Nicoderm) AB - BACKGROUND: Transdermal nicotine therapy has shown promise as a smoking cessation aid, but questions about its contact sensitization potential and long-term topical safety have been raised. The purpose of this study was to determine the contact sensitization potential of one nicotine transdermal system (Nicoderm, Marion Merrell Dow Inc, Kansas City, Mo, and ALZA Corporation, Palo Alto, Calif) in a population who were allowed to continue smoking. METHODS: This study comprised two phases separated by a 2-week rest interval. During phase 1, a 42 day open-label induction period, subjects wore only active transdermal nicotine systems. During phase 2, a 4-day double-blind challenge period, subjects wore active and placebo systems concurrently. Upon removal of each patch, skin sites were evaluated for signs of irritation, and subjective complaints such as itching or burning were recorded. RESULTS: Of the 186 subjects completing the study, 3 (1.6%) exhibited evidence of delayed contact sensitization manifested as erythema with or without infiltration and confined solely to sites of active transdermal nicotine system application. Nonallergic skin irritation was observed in less than 3% of all applications. All reactions resolved without incident. No subjects developed systemic reactions. CONCLUSIONS: The transdermal nicotine system used in this trial had a low contact sensitization incidence and was well tolerated topically with minimal irritation. PMID- 1593245 TI - Smokeless tobacco use and oral pathology in a professional baseball organization. AB - BACKGROUND: Smokeless tobacco has been implicated as a risk factor for numerous oral conditions. Since baseball players are known to have a high incidence of smokeless tobacco use, they are an excellent group in which to study the effects of smokeless tobacco on the oral cavity. We report our findings in 206 of 220 eligible men during spring training of a professional baseball organization. Major and minor league ballplayers, coaches, and management personnel were included. METHODS: Participants completed a 2-page, 23-item questionnaire on smokeless tobacco use. This was followed by a detailed examination for oral leukoplakia, periodontal disease, and dental caries performed by a physician who was blinded to the results of the questionnaire. Oral leukoplakia was graded I, II, or III according to severity. RESULTS: Eighty-eight of 206 participants (42.7%) reported current use of smokeless tobacco; 62 of these men used smokeless tobacco year round, while 26 used smokeless tobacco only during the baseball season. The 88 smokeless tobacco users often used more than one form of tobacco. Moist snuff was the most common form (73.9% of users) followed by loose leaf tobacco (53.4%) and plug tobacco (9.1%). Oral leukoplakia was found in 25 of 88 current users (28.4%). Only the year-round users, however, had an incidence rate (37.1%) that was significantly different from all others (odds ratio = 9.35, 95% CI = 3.46 to 26.21). Year-round users were also more likely to have a higher grade of oral leukoplakia. Periodontal disease and dental caries were no more prevalent among smokeless tobacco users than nonusers. CONCLUSIONS: We conclude that the use of smokeless tobacco products is a significant risk factor for the development of oral leukoplakia, and that this risk is greatest in those individuals who use smokeless tobacco continuously throughout the year. PMID- 1593246 TI - Increasing physician screening and counseling for passive smoking. AB - BACKGROUND: The adverse health effects of passive smoking on children, including increased respiratory tract illnesses and otitis media, are well documented. A child's visit to a physician for these illnesses represents a "teachable moment" to screen for household smokers and to counsel parents regarding the health effects of passive smoking. Whether physicians are performing these activities in their offices is unknown. We hypothesized that screening and counseling by physicians with regard to passive smoking would be low in this setting and that these activities could be increased by a simple, two-part intervention. METHODS: We used chart audits and postvisit parental surveys to assess the preintervention and postintervention screening and counseling activities of physicians with regard to passive smoking. The two-part intervention consisted of a 2-hour educational seminar for the physicians and a passive smoking chart reminder and documentation system. RESULTS: In comparing the preintervention with the post intervention parental surveys, there were increases in the passive smoking screening (17% vs 32%, P = .03) and counseling (19% vs 46%, P = .03) activities of physicians. Chart documentation of these activities, however, showed very little change regarding screening (2% vs 6%, P = .19) or counseling (4% vs 6%, P = .64). CONCLUSIONS: These results indicate initially low rates of passive smoking screening and counseling of parents by physicians during acute illness visits of their children. These data also indicate that a simple two-part intervention was very useful in increasing passive smoking screening and counseling activities by physicians in this setting. PMID- 1593247 TI - Hospital efforts in smoking control: remaining barriers and challenges. AB - BACKGROUND: This study reports the barriers and challenges for hospital tobacco control efforts after the institution of smoke-free policies. METHODS: Surveys of employees and inpatients of five hospitals in Augusta, Georgia, were conducted and evaluated 4 months after joint hospital implementation of smoke-free policies. A random sample of 1997 employees and a convenience sample of 517 inpatients returned usable surveys. RESULTS: Although attitudes to the hospital bans on smoking reflected strong support for smoke-free policies, four out of five hospitals reported significant implementation problems. Despite the bans, 49% of patients who were smokers continued to smoke while hospitalized, and almost one half of all hospitalized smokers had received no advice to quit smoking from a physician or a nurse since admission. Employees and patients both agreed that the smoke-free policies had benefited employees more than patients. CONCLUSIONS: Despite achieving a smoke-free status, there are many challenges that remain for comprehensive hospital tobacco-control efforts. Hospitals and health care professionals must remain particularly alert and attentive to the needs of patients and employees still addicted to tobacco. PMID- 1593248 TI - Patient referral to a smoking cessation program: who follows through? AB - BACKGROUND: While health care providers are often urged to refer smokers to a smoking cessation program, little information is available about patient adherence to such advice. METHODS: A group of primary care patients who smoked (N = 1380) received brief advice to quit from their provider, and were then asked to stay and talk to a counselor for more information. Counselors randomly delivered one of two interventions. For the intervention group, referral to a specific group cessation program was emphasized, and for the control group, quitting advice was merely repeated. The referral intervention included a video in which role models testified to the acceptability and usefulness of the HMO's group program. The usual program fees were waived, and patients received a supportive, follow-up telephone call 1 week after their visit. RESULTS: In the referral intervention group, 53.2% of patients agreed to go to the cessation program and 11.3% actually attended, compared with only .006% of the patients who received advice only. Logistic regression analyses revealed that patients who were contemplating quitting were more than five times as likely to respond to the referral compared to precontemplators (smokers who were not seriously considering quitting). Older, heavier smokers were also more likely to attend a group session. CONCLUSIONS: An intensive, specific referral to a group smoking cessation program can increase participation by patients. Most patients, however, will not attend a group program; therefore, a brief office-based intervention for all smokers should precede referral. PMID- 1593249 TI - Improving smoking cessation counseling by family practice residents. AB - BACKGROUND: While programs to train residents in smoking cessation counseling skills have been devised, few have assessed trainee behavioral changes in practice settings where residents were blind to the evaluation of their behavior. This study assessed the effectiveness of a training program in smoking cessation counseling and chart-prompting system in increasing the frequency and quality of counseling by residents at three clinic sites. METHODS: Twenty-eight residents participated in a training program that included epidemiology, discussion of attitudes, counseling techniques, videotaped examples, and small group role play. The chart-prompting system was implemented at two clinics 1 month after training. Patient exit interviews, during which information on resident counseling on smoking cessation was obtained, were conducted before training, after training, at 3-month follow-up, and at 6-month follow-up. Questionnaires assessing knowledge, attitudes, and self-perceived counseling behaviors were completed by residents at pretraining, posttraining, and 6-month follow-up periods. RESULTS: Interviews with 517 smokers were analyzed. Results showed an increase in counseling at 3-month follow-up but a regression toward baseline at 6 months. Counseling improved at clinics where chart prompting was initiated. The number of counseling behaviors decreased when the number of patients seen increased. Whether a patient received counseling was positively associated with prior contact with the physician. There was no correlation between resident self perception and patient report. CONCLUSIONS: A training program in smoking cessation counseling and a chart-prompting system did not result in a lasting change in resident behavior. System factors may play an important role in long term behavior change. PMID- 1593250 TI - Preventing teenage tobacco addiction. AB - Tobacco use remains a major health problem among children and adolescents. Restrictive school policies on tobacco use and enforcement of laws prohibiting the sale of tobacco to minors can produce substantial reductions in tobacco use among this population. This article provides practical, step-by-step instructions to help physicians get these policies implemented in their communities. PMID- 1593251 TI - A physician's guide to smoking cessation. AB - Claims of the effectiveness of smoking cessation services and products are often misleading. It is important that physicians be well informed in order to make appropriate recommendations to their patients who smoke. In this article smoking cessation products and programs are critically evaluated and issues such as cure rates and validation of self-reported abstinence are discussed. Many commercial products are available to aid in cessation, although none has been proven effective. With the exception of nicotine polacrilex gum and transdermal patches in conjunction with a multicomponent clinic, medications are generally ineffective. Smoking cessation programs range from the provision of self-help materials to multisession groups and clinics. Multicomponent, behavioral-based group programs have been the most successful. Physicians should raise the issue of smoking cessation as frequently as possible with smokers and should recommend the use of smoking cessation products and services as appropriate. Referrals should be made to programs that base their success rates on scientifically accepted standards, including a 1-year follow-up, inclusion of dropouts and nonrespondents in calculating outcome, and biochemical validation of self reported abstinence. Reports of success rates of 80% to 95% at the end of a 1 year program should be viewed with skepticism. Ideally, whether working independently or through referral, the physician should actively promote smoking cessation for all patients who smoke. PMID- 1593252 TI - Septic discitis resulting from Escherichia coli urosepsis. AB - Septic discitis refers to a primary suppurative process involving the intervertebral disc space and occurs as a result of hematogenous invasion or contamination by pyogenic organisms. A case of septic discitis is described in a 77-year-old woman following an episode of Escherichia coli urosepsis. Despite bed rest, an orthosis, and appropriate antibiotics, the patient ultimately had to undergo surgical disc removal. The diagnosis of septic discitis is often made in the context of other diseases that share common clinical and laboratory findings. Magnetic resonance imaging appears well suited for diagnostic confirmation of septic discitis. Needle biopsy and aspiration results should be used to determine the appropriate choice of antibiotic for this disease process. PMID- 1593254 TI - Murder in south London: a novel use of DNA profiling. AB - Lorraine Benson's body was found beaten and strangled at Raynes Park, Surrey, in December 1988. Considering the possibility of linked offences, a murder squad was set up to work alongside a team already investigating a rape series in the Kingston area. A man's handkerchief left at a site a quarter of a mile from the murder scene was found to be stained with blood and saliva matching that of the victim. A DNA profile was obtained from a stain of nasal mucus on this handkerchief and found to match a suspect later arrested for an attempted rape in the same locality. Also of forensic interest were dust marks made by the zips of the victim's and defendant's coats and identification of the rope used for strangulation. PMID- 1593253 TI - Shoe wear patterns and pressure distribution under feet and shoes, determined by image analysis. AB - A method is outlined for extracting contours of the pressure exerted by feet on the ground, either directly or through the soles of shoes, and of the wear patterns on shoe soles. The method is applied to two types of image: shoeprint images made in the laboratory, and pedobarography images recording the distribution of pressure under the foot during a footstep. The first procedure in extracting the information from images involves low pass filtering in the Fourier domain, performed by a microcomputer and frame-grabbing system. The boundaries of the regions in the resultant images are then extracted from the filtered images to display the shape of constant pressure areas and of the general shoe-wear. PMID- 1593255 TI - Evaluating DNA profiles in a case where the defence is "it was my brother". AB - The widespread application of DNA profiling has brought to some prominence the issue of close relatives sharing body fluid types. In a particular crime case it may be suggested that a close relative of the suspect was the person responsible. This paper explains how an assessment may be made in the context of single locus profiling and where the suggestion is that a full sibling is involved. A formula is established for the likelihood ratio which is then worked out in detail for the particular case where the suspect profile has two distinct bands. Generalization to other types of case is briefly explained and there is a short discussion of the impact of the evidence in the context of a trial. For all parties, justice will best be done if the scientist has ample notice, before the trial, of relationship issues such as this one. PMID- 1593256 TI - Mycoplasma adhesion. PMID- 1593257 TI - Anaerobic 2-ketogluconate metabolism of Klebsiella pneumoniae NCTC 418 grown in chemostat culture: involvement of the pentose phosphate pathway. AB - Under anaerobic 2-ketogluconate-limited growth conditions (D = 0.1 h-1), Klebsiella pneumoniae NCTC 418 was found to convert this carbon source to biomass, acetate, formate, CO2, ethanol and succinate. The observed fermentation pattern is in agreement with the simultaneous functioning of the pentose phosphate pathway and the Entner-Doudoroff pathway in 2-ketogluconate catabolism. When cultured at pH 8.0 apparent YATP values were lower than those found at culture pH 6.5. This difference can be explained by assuming that at high culture pH values approximately 0.5 mol ATP was invested in the uptake of 1 mol 2 ketogluconate. Sudden relief of 2-ketogluconate-limited conditions led to lowering of the intracellular NADPH/NADP ratio and (possibly as a result of this) to inhibition of biosynthesis. Whereas production of ethanol stopped, lactate was produced at high rate. This product was formed, at least partly, via the methylglyoxal bypass. PMID- 1593258 TI - Linear growth and poly(beta-hydroxybutyrate) synthesis in response to pulse-wise addition of the growth-limiting substrate to steady-state heterotrophic continuous cultures of Aquaspirillum autotrophicum. AB - Heterotrophic pyruvate-limited steady-state continuous cultures of the bacterium Aquaspirillum autotrophicum were perturbed with a pulse injection of a small volume of concentrated pyruvate solution. These cultures exhibited an instantaneous change in the growth dynamics, turning from steady state to apparently linear growth. These transient growth-responses had no lag phase and were clearly distinct from unlimited exponential growth according to the initial rates of increase of biomass and substrate disappearance kinetics. A linear accumulation with time of poly(beta-hydroxybutyrate) was observed within the cells. Slopes of these linear responses were negatively correlated with the dilution rate. Physiological bases of linear growth are discussed in the light of the models of H. E. Kubitschek. Poly(beta-hydroxybutyrate) synthesis in the absence of exogenous limitation may serve to protect the cells against a transient metabolic overflow. PMID- 1593259 TI - Temperature adaptation in Lactobacillus fermentum: interconversions of oleic, vaccenic and dihydrosterulic acids. AB - The interchange of octadecenoic acids and dihydrosterulic acid was a response of aerobically growing Lactobacillus fermentum to changes in growth temperature. Oleic and vaccenic acid contents decreased both at temperatures below 20 degrees C and above 26 degrees C, showing mirror image behaviour, with a concomitant increase in dihydrosterulic acid. A temperature-dependent shift from vaccenic to oleic acid synthesis, and the conversion of the latter to dihydrosterulic acid was responsible for the overall change. Consequently, the degree of fatty acid unsaturation decreased at temperatures above 26 degrees C, whereas the degree of cyclization increased. The converse occurred below 20 degrees C. The relative amount of lactobacillic acid, total cellular fatty acid content, and mean fatty acid chain length were practically temperature-independent. The occurrence of oleic acid is thought to be related to aerobic growth conditions. PMID- 1593260 TI - Expansion of the Candida albicans cell envelope in different morphological forms of the fungus. AB - Modes of cell envelope expansion were monitored in developing cells of Candida albicans 73/055 to which polystyrene beads were attached. Eight different conditions of culture medium, pH and temperature were used to promote growth in a variety of morphological forms. The cells were observed microscopically during growth in Sykes-Moore perfusion chambers, and sequential measurements of distances between the bead and the parent cell, and the bead and the apical tip were used to distinguish apical envelope expansion from general envelope expansion. Morphology index (Mi) was determined at each time point as an estimate of each cell's morphology. Calculations based on the measurements showed that general envelope expansion was inversely proportional to Mi, but that general expansion greater than 20% occurred only in cells with a final Mi less than 2.0, indicating that regulation of apical and general envelope expansion alone may be insufficient to determine the different morphologies seen in cells with higher Mi. The rate of expansion of the perimeter of cells was linearly proportional to the final Mi. This observation suggests that commitment to morphological development in C. albicans may in part involve commitment to a rate of envelope expansion, which itself helps determine the final morphology of a cell. PMID- 1593261 TI - Molecular cloning and sequencing of the beta-isopropylmalate dehydrogenase gene from the cyanobacterium Spirulina platensis. AB - The gene for beta-isopropylmalate dehydrogenase (EC 1.1.1.85) of Spirulina platensis (leuB) was cloned from a lambda EMBL3 genomic library by heterologous hybridization using the Nostoc UCD 7801 leuB gene as a probe. The sequence of the entire leuB coding region was determined as well as 645 bp of 5' flanking region and 956 bp of 3' flanking region. DNA sequencing revealed an open reading frame of 1065 nucleotides capable of encoding a polypeptide of 355 amino acids. Homologies between the amino acid sequence deduced from the nucleotide sequence of the S. platensis leuB gene and the amino acid sequences published for corresponding proteins either from bacteria or yeasts are 45% or more. Northern hybridization analysis indicated that the S. platensis leuB gene is transcribed as a single monocistronic RNA of approximately 1200 bases. PMID- 1593262 TI - Purification of the acidic pectate lyase and nucleotide sequence of the corresponding gene (pelA) of Erwinia chrysanthemi strain 3937. AB - The pelA gene from Erwinia chrysanthemi strain 3937, which encodes the acidic pectate lyase, PLa, has been sequenced and characterized. The structural gene consists of a 1179 bp open reading frame encoding a polypeptide of 41,555 Da, which includes an N-terminal signal peptide. The deduced amino acid sequence shows a protein very similar to some PLs already sequenced. Cloning of the pelA gene behind the lacZ promoter of the vector pTZ19R allowed overexpression of PLa into a derivative of strain 3937 deleted of the other pel genes. The mature protein was obtained in milligram amounts from the supernatant of this strain and at homogeneous purity after two purification steps. Its biochemical properties were similar to those of other PLs. Polyclonal antibodies raised against the purified PLa cross-reacted with the basic pectate lyase PLd, but not with PLe. The role of PLa in pathogenicity is discussed. PMID- 1593263 TI - Copper-zinc superoxide dismutase in Haemophilus species. AB - Copper-zinc superoxide dismutases ([Cu,Zn]-SODs) are ubiquitous in eukaryotes but have rarely been found in prokaryotes. A gene for [Cu,Zn]-SOD (sodC) has recently been cloned from Haemophilus influenzae type b and H. parainfluenzae, so other Haemophilus and related species were screened for the presence of [Cu,Zn]-SODs by visualization of bands of SOD activity in non-denaturing polyacrylamide gels and by gene probing. Strains of H. aphrophilus, H. paraphrophilus, H. haemolyticus, H. paraphrohaemolyticus, some non-typable H. influenzae, H. haemoglobinophilus (canis) and H. parasuis were all found to have [Cu,Zn]-SOD activity (inhibited by 2 mM-cyanide) in polyacrylamide gels. In a Southern blot analysis, DNA from H. aphrophilus, H. paraphrophilus, H. haemolyticus and [Cu,Zn]-SOD-containing non typable H. influenzae--but not the other species--hybridized to a 360 nucleotide DNA probe containing the 5'-part of sodC cloned from H. influenzae type b. Bacterial [Cu,Zn]-SODs are more prevalent than has previously been recognized. PMID- 1593264 TI - Identification of a third genomic group of Borrelia burgdorferi through signature nucleotide analysis and 16S rRNA sequence determination. AB - As part of a continuing effort to assess genetic variation among isolates of Borrelia burgdorferi we have determined the 16S rRNA signature nucleotide makeup of two tick isolates from the USSR. Signature nucleotides were identified via reverse transcriptase primer extension sequencing of select regions of the 16S rRNA molecule. In addition, the near complete 16S rRNA sequence of one of the isolates, R-IP3, was determined and utilized in a phylogenetic assessment. The sequence was aligned with the 16S rRNA sequences of other B. burgdorferi isolates as well as with other Borrelia species. Distance matrix analyses were performed and a phylogenetic tree was constructed. These analyses demonstrate that these isolates belong to a third previously unidentified genomic group of B. burgdorferi. PMID- 1593265 TI - Serum protease cleavage of Bacillus anthracis protective antigen. AB - The protective antigen component of anthrax lethal toxin, produced in vitro, has a molecular mass of 83 kDa. Cell-culture studies by others have demonstrated that upon binding of the 83 kDa protective antigen to cell-surface receptors, the protein is cleaved by an unidentified cell-associated protease activity. The resultant 63 kDa protein then binds lethal factor to form lethal toxin, which has been proposed to be internalized by endocytosis. We found that, in the blood of infected animals, the protective antigen exists primarily as a 63 kDa protein and appears to be complexed with the lethal factor component of the toxin. Conversion of protective antigen from 83 to 63 kDa was catalysed by a calcium-dependent, heat-labile serum protease. Except for being complexed to protective antigen, there was no apparent alteration of lethal factor during the course of anthrax infection. The protective antigen-cleaving protease appeared to be ubiquitous among a wide range of animal species, including primates, horses, goats, sheep, dogs, cats and rodents. PMID- 1593266 TI - Influence of the carbon source on nisin production in Lactococcus lactis subsp. lactis batch fermentations. AB - Nisin production by Lactococcus lactis subsp. lactis NIZO 22186 was studied in batch fermentation using a complex medium. Nisin production showed primary metabolite kinetics: nisin biosynthesis took place during the active growth phase and completely stopped when cells entered the stationary phase. A stringent correlation could be observed between the expression of the prenisin gene (nisA) and the synthesis of the post-translationally enzymically modified and processed mature nisin peptide. Moreover, it seemed likely that nisin had a growth control function. A physiological link is proposed between sucrose fermentation capacity and nisin production ability. Carbon source regulation appears to be a major control mechanism for nisin production. PMID- 1593267 TI - Isolation and partial characterization of haemagglutinins from plasmodia of Physarum polycephalum. AB - The soluble haemagglutinins produced by plasmodia of Physarum polycephalum were purified by chromatographic methods and resolved into haemagglutinins I and II. On SDS-PAGE, purified haemagglutinins I and II each gave a single band with an apparent molecular mass of 6 and 11 kDa, respectively. The results of gel filtration chromatography suggested that both haemagglutinins were dimers of the respective subunits under non-denaturing conditions. Rabbit erythrocytes were preferentially agglutinated by both haemagglutinins. The human type A, B and O erythrocytes were agglutinated by haemagglutinin II to an equal degree but were not agglutinated by haemagglutinin I. Simple sugars failed to inhibit the activities of both haemagglutinins. The activities, however, were effectively inhibited by the addition of thyroglobulin. Other glycoproteins such as fetuin, orsomucoid and transferrin inhibited the activity of haemagglutinin I but not that of haemagglutinin II. These haemagglutinins were detected in a slime fraction obtained from the culture media of starved plasmodia, suggesting that they are released to the outside of the plasmalemma to become associated with the slime layer on the plasmodial surface. PMID- 1593268 TI - Detection of intracellular forms of secretory aspartic proteinase in Candida albicans. AB - The extracellular proteinase (EPR) of Candida albicans was induced in a medium containing bovine serum albumin as sole nitrogen source. There were two intracellular forms in cells induced to produce EPR, a 43 kDa protein (EPR) and a 45 kDa protein (cross-reacting material of EPR; CRM-EPR); these were detected by immunoblotting using anti-EPR antiserum. The 43 kDa protein (EPR) may be the same as the extracellular form judging by molecular mass, and the 45 kDa protein (CRM EPR) may be a precursor form of EPR. Many dense granules were observed by electron microscopy near the plasma membrane of the mother cells in EPR-producing cells. Both the 43 and 45 kDa proteins were recovered in a membrane fraction and were solubilized by Triton X-100. When the membrane fraction was further fractionated by sucrose density gradient centrifugation, the 43 and 45 kDa proteins were differentially fractionated. This suggests that they were located in different membrane-bound structures and is consistent with an assumption that the 45 kDa protein is a precursor for EPR. PMID- 1593269 TI - Physical mapping of the mec region of an Australian methicillin-resistant Staphylococcus aureus lineage and a closely related American strain. PMID- 1593270 TI - Paranormal experiences in the general population. AB - The Dissociative Disorders Interview Schedule was administered to a random sample of 502 adults in the general population of Winnipeg, a midwestern Canadian city. Results showed that paranormal/extrasensory experiences were common in the general population. They were linked to a history of childhood trauma and to other dissociative symptom clusters. A factor analysis of the paranormal experiences identified three factors which together accounted for 44.0% of the combined variance of the scores. A model is proposed in which paranormal experiences are conceptualized as an aspect of normal dissociation. Like dissociation in general, paranormal experiences can be triggered by trauma, especially childhood physical or sexual abuse. Such experiences discriminate individuals with childhood trauma histories from those without at high levels of significance. PMID- 1593271 TI - Generalized anxiety disorder vs. panic disorder. Distinguishing characteristics and patterns of comorbidity. AB - In order to examine the validity of the distinction between generalized anxiety disorder (GAD) and panic disorder (PD) we compared 41 subjects with GAD and 71 subjects with PD. The GAD subjects had never had panic attacks. In contrast to the symptom profile in PD subjects suggestive of autonomic hyperactivity, GAD subjects had a symptom pattern indicative of central nervous system hyperarousal. Also, subjects with GAD had an earlier, more gradual onset of illness. In terms of coexisting syndromes, GAD subjects more often had simple phobias, whereas PD subjects more commonly reported depersonalization and agoraphobia. GAD subjects more frequently had first-degree relatives with GAD, whereas PD subjects more frequently had relatives with PD. A variety of measures indicated that our GAD subjects had a milder illness than those with PD. Also, fewer GAD subjects gave histories of major depression than did PD subjects. Among GAD subjects, coexisting major depression was associated with simple phobia and thyroid disorders and among PD subjects, comorbid depression was associated with social phobia and hypertension. Our findings indicate that the separation of GAD from PD is a valid one. They also indicate that, within disorders, unique patterns of comorbidity may exist that are important both clinically and theoretically. PMID- 1593272 TI - Diagnostic patterns of social phobia. Comparison in Tokyo and Hawaii. AB - A comparison was made of the diagnosis of social phobia by Japanese psychiatrists in Tokyo and American psychiatrists in Hawaii. A brief segment of videotaped interviews and written case histories of four Japanese patients from Tokyo and two Japanese-American patients from Hawaii, who were clinically diagnosed with social phobia, were presented to the clinicians for their diagnosis. Japanese psychiatrists tended to diagnose social phobia congruently for the Japanese cases but not for the Japanese-American cases. American psychiatrists tended to diagnose various categories including anxiety disorder and avoidant personality disorder, in addition to social phobia, disregarding the ethnic background of the patients. This illustrates that the diagnostic pattern for social phobia varied considerably between psychiatrists of these two countries. The reasons considered are the patient's cardinal symptom manifestation, style of problems presentation, as well as the clinician's professional orientation and familiarity to this particular disorder. PMID- 1593273 TI - Hwa-byung. A community study of Korean Americans. AB - One hundred nine Korean American community subjects were interviewed regarding their experiences with hwa-byung (HB), a Korean folk illness label commonly used by Koreans with a myriad of physiological and psychological complaints. During these interviews, standard instruments were also used to assess their depressive and somatic symptoms. The results indicated that a relatively high proportion (12%) of the subjects labeled themselves as having suffered from HB. While no apparent sociodemographic differences were found between HB and non-HB subjects, significantly more HB subjects fulfilled the diagnosis of DSM-III major depression and also had previous diagnoses of depression. The HB subjects also had significantly higher scores for the total, depressive, and somatic subscales and 16 of the 20 individual items of the Center for Epidemiologic Studies Depression Scale. These data confirm previous observations of substantial overlap between HB and DSM-III major depression among Koreans and Korean Americans, and suggest that HB may be a culturally patterned way of expression for Koreans experiencing major depression and related conditions. The clinical and theoretical implications of these findings are also discussed. PMID- 1593274 TI - Subtypes of psychiatric inpatient women who have been sexually abused. AB - The sexual abuse histories of 171 women admitted to a psychiatric inpatient service revealed that 40.3% had a positive history of sexual abuse. The DSM-III diagnoses made on discharge were not related to presence of abuse, age of abuse onset, duration and frequency of abuse, or relationship of the victim to the perpetrator. However, the diagnosis of personality disorder was associated with greater invasiveness of sexual abuse. Cluster analysis of the MMPIs provided by these women revealed four clusters. Membership in the more disturbed cluster was associated with a history of sexual abuse, but not with invasiveness, age of onset, relationship to the perpetrator, or duration and frequency of abuse. The implications of these findings for the role of mitigating factors, such as coping style and adaptation to stress, are discussed. PMID- 1593275 TI - Spontaneous seizure activity as a complication of unilateral electroconvulsive therapy: a case report and brief review of the literature. PMID- 1593276 TI - Validating self-reports of mental health service use in a chronic population. PMID- 1593277 TI - alpha-Tocopherol treatment for tardive dyskinesia. PMID- 1593278 TI - Metabolism of the Catharanthus alkaloids: from Streptomyces griseus to monoamine oxidase B. AB - More than three decades after their discovery and implementation in medicine, essentially nothing is known about the metabolism or the implications of metabolism in mechanism of action or toxicity of the Catharanthus alkaloids. The frustrating paucity of information about pathways of metabolism has limited a major source of structure-activity relationship information and has blocked a critical avenue necessary for the logical development of new and more useful Catharanthus alkaloids. Microbial transformations, peroxidases, copper oxidases, mouse and rat cytochrome P-450 systems, and mouse brain and bovine liver monoamine oxidase (MAO) preparations have been explored in the study of Catharanthus alkaloid metabolism. In this report, we present results which have clarified the involvement of enzymatic and chemically catalyzed one-electron oxidations that yield nitrogen-centered cation radicals, iminium, and carbinolamine intermediates, all of which explain how new carbon-carbon and carbon-oxygen bonds form, or break and rearrange. The dimeric Catharanthus alkaloids are recalcitrant to oxidations catalyzed by monoamine oxidases and to both normal and induced P-450 rat microsomal preparations. However, the Catharanthus alkaloids appear to be selective reversible inhibitors of MAO-B. Chemical and biochemical aspects of the metabolic transformations of dimeric Catharanthus alkaloids are reviewed together with the implications of our findings. PMID- 1593279 TI - Anti-influenza virus effect of some propolis constituents and their analogues (esters of substituted cinnamic acids). AB - The antiviral activity of six synthetic substances, esters of substituted cinnamic acids, identical with or analogous to some of the constituents of the Et2O fraction of propolis was studied in vitro. One of them, isopentyl ferulate, inhibited significantly the infectious activity of influenza virus A/Hong Kong (H3N2) in vitro and the production of hemagglutinins in ovo. By the use of diverse experimental patterns, it was found that the maximal inhibition of viral reproduction was observed when test substances were present in the medium during the whole infectious process. PMID- 1593280 TI - Constituents of Azadirachta indica: isolation and structure elucidation of a new antibacterial tetranortriterpenoid, mahmoodin, and a new protolimonoid, naheedin. AB - Mahmoodin [1], a new limonoid, has been isolated from Azadirachta indica (neem) oil, along with seven known tetranortriterpenoids, azadirone, epoxyazadiradione, nimbin, gedunin, azadiradione, deacetylnimbin, and 17-hydroxyazadiradione. A new protolimonoid, naheedin [3], has been obtained from the neem fruits along with azadirachtol. Their structures have been elucidated through chemical and spectral analyses including 2D nmr studies. The absolute configuration of 1 was established by comparison of its cd spectrum with those of the known tetranortriterpenoids. Mahmoodin showed significant antibacterial activity against various Gram-positive and Gram-negative organisms. Four hydrocarbons, icosane, docosane, 2-methyltricosane, and docosene, have also been identified by gc-ms of the EtOH extract of the fruit coats. Only docosane has earlier been reported from neem, while the remaining three are unreported from this plant. PMID- 1593281 TI - Additional bioactive compounds and trilobacin, a novel highly cytotoxic acetogenin, from the bark of Asimina triloba. AB - Fractionation of the EtOH extract of the bark of Asimina triloba, monitoring by brine shrimp lethality, has led to the isolation and structural elucidation of a novel highly cytotoxic Annonaceous acetogenin, trilobacin [1], in addition to six known compounds: asimicin 2], bullatacin [3], bullatacinone [4], N-p coumaroyltyramine [5], N-trans-feruloyltyramine [6], and (+)-syringaresinol [7]. Acetogenin 1 was identified as a diastereomer of asimicin [2] by spectral and chemical methods, and both 1 and 2 showed potent and selective cytotoxicities in the NCI human tumor cell line screen. PMID- 1593282 TI - Isolation of potential cancer chemopreventive agents from Eriodictyon californicum. AB - Activity-based fractionation of Eriodictyon californicum resulted in the isolation of 12 flavonoids that inhibit the metabolism of the carcinogen benzo[a]pyrene by hamster embryo cells in tissue culture. One was identified as a new flavanone, 3'-methyl-4'-isobutyryleriodictoyol [1], on the basis of spectroscopic analysis and alkaline hydrolysis. The seven other active flavanones were identified as eriodictyol [2], homoeriodictyol [3], 5,4'-dihydroxy-6,7 dimethoxyflavanone [4], pinocembrin [5], sakuranetin [6], 5,7,4'-trihydroxy-6,3' dimethoxyflavanone [7], and naringenin 4'-methyl ether [8]. Four active flavones were also isolated: cirsimaritin [9], chrysoeriol [10], hispidulin [11], and chrysin [12]. The high inhibition of benzo[a]pyrene metabolism and the activation of benzo[a]pyrene to ultimate carcinogenic DNA-binding metabolites by cirsimaritin and chrysoeriol at a concentration of only 10 micrograms/ml indicates that these flavones warrant further investigation in vivo as potential chemopreventive agents. PMID- 1593283 TI - Isolation of the bioactive terpene 7-deacetoxy-olepupuane from the temperate marine sponge Dysidea sp. PMID- 1593284 TI - Ichthyotoxic diterpenoids from the Cantabrian nudibranch Chromodoris luteorosea. AB - Five spongian diterpenoids 2, 3, 6-8, previously found in sponges and nudibranchs from very distinct geographical areas, have been isolated from the Cantabrian nudibranch Chromodoris luteorosea. The terpenoids are mainly localized along the border of the mantle of the mollusk. All the diterpenoids are toxic to Gambusia affinis. PMID- 1593285 TI - Patellamide E: a new cyclic peptide from the ascidian Lissoclinum patella. AB - A new cyclic peptide, patellamide E [1], was isolated from the ascidian Lissoclinum patella collected at Pulau Salu, Singapore. Its structure was determined by nmr spectroscopy, and its absolute configuration by acid hydrolysis and analysis of the derivatized constituent amino acids by hplc. Patellamide E was mildly cytotoxic against human colon tumor cells in vitro. PMID- 1593286 TI - (-)-agelasidine C and (-)-agelasidine D, two new hypotaurocyamine diterpenoids from the Caribbean sea sponge Agelas clathrodes. AB - Two new diterpene derivatives of hypotaurocyamine, (-)-agelasidine C [3] and (-) agelasidine D [5], have been isolated from the Caribbean sea sponge Agelas clathrodes. The structures of 3 and 5 have been established by interpretation and comparison of their spectral data to those of the known antipode (+)-agelasidine C [1]. PMID- 1593287 TI - Striving for excellence through quality improvement. AB - Numerous factors are affecting health care services today, including increased consumer awareness; growth of medical technology; rising costs and an unpredictable financial market; a continued shortage of health care professionals, especially nurses; and a shift of many services from inpatient to outpatient settings. As a result, American health care is undergoing rapid change. This article explores how one management concept--quality improvement- can help foster innovative, effective, and efficient change in today's health care organizations. PMID- 1593289 TI - Managed care. PMID- 1593288 TI - Implementing career development in a drug prevention program. AB - This article describes an innovative school and community based drug prevention program aimed at high risk urban youths. It is the result of the collaborative efforts of the nursing faculty of Lehman College-CUNY and the assistant district attorneys of the Office of the District Attorney of Bronx County. In the program, children learn first hand about career opportunities in nursing and law, and gain incentives to remain drug free. PMID- 1593291 TI - Medical guidelines for hazardous waste workers. PMID- 1593290 TI - Environmental scanning: a strategy for the future. AB - The rapidity of change confronting nursing at all levels will continue to challenge nursing's ultimate capacity to adapt and remain a viable profession in the 21st century. The process of meeting the challenges can be proactive based on assessment of needs and available resources, or reactive based on the reaction to challenges. A strategy identified by the authors that can be used at all levels of nursing practice, administration, education, and research is environmental scanning. This methodology has been used effectively in other disciplines for strategic, long-term planning and can be readily adapted to a wide variety of nursing service, academic, or professional associations. PMID- 1593292 TI - The ergonomic challenge of repetitive motion with varying ergonomic stresses. Characterizing supermarket checking work. AB - Many jobs leading to a risk of cumulative trauma do not have highly stereotyped motions. This study developed and employed a novel method of ergonomic characterization to describe quantitatively the actions associated with grocery checking. Fifty workers were videotaped for three 15-minute segments each. Eight object types were selected to represent the variety of items in a supermarket. Nine types of motion were coded for each of the eight objects for 10 replications for each subject. The motions coded were: grip type (power versus pinch), wrist flexion, wrist extension, radial deviation, ulnar deviation, supination, pronation, body (lumbar) flexion, and drag versus lift. The results were then weighted according to relative frequency of the object type. In this manner, an ergonomic risk index can be assigned to each specific object type. This method permits identification of objects presenting the greatest risk. It also allows specificity of preventive interventions (object redesign, work practice change) as well as providing a quantitative measure to evaluate work station redesign. Furthermore, it has the potential of quantitatively describing the risk of each individual worker. PMID- 1593293 TI - Evaluation of chemically sensitive patients. AB - An increasing number of patients have been presenting with multiple symptoms they attribute to low-level chemical exposures, ie, multiple chemical sensitivities (MCS). Although some studies have evaluated such patients, the selection criteria has not been rigorously defined. The present study is the first to use a relatively rigorous definition of MCS to select patients for study. Comprehensive evaluation of medical, psychiatric, neuropsychological, and immunological status of a series of MCS patients is presented. In contrast to previous studies, patients in this study did not have a history of psychiatric disorder. However, some patients were currently depressed. Neuropsychological assessment did not reveal any abnormalities with the exception of one test of verbal memory for which performance was consistently poor relative to the normative sample. No significant immunological abnormalities were noted. PMID- 1593294 TI - Evaluation of the audioscope in an industrial setting. AB - In this study, the findings of a 25 dB hearing level Welch Allyn Audioscope test at 0.5, 1, 2, 4 kHz were compared with the standard of conventional pure-tone audiometry in 228 newly hired construction workers. The sensitivity for all frequency-specific comparisons combined was found to be lower than in previous studies done in a nonoccupational setting. After correction for sampling bias, the specificity for all frequencies combined was well within the range reported in other studies. Only 1.9% of ears (1/53) that were able to hear all four audioscope frequencies were found by conventional audiometry to have clinically important hearing loss defined as a 25 dB hearing level averaged over the speech frequencies. Hence, the audioscope can be used as a rapid initial test in workers who otherwise would not have access to hearing screening. PMID- 1593295 TI - Constant incidence rates of needle-stick injury paradoxically suggest modest preventive effect of sharps disposal system. AB - Does placement of impenetrable sharps disposal systems in hospitals reduce needle stick injury? To study this question, annual health questionnaires were distributed on a quarterly basis to all 8000 employees in an academic medical center in a large eastern US metropolitan city asking each employee whether he or she had experienced a needle-stick injury since the last questionnaire. Questionnaires from active floor nurses were separated and hand tallied in 1987, 1989, and 1990, the latter 2 years being after impenetrable sharps disposal systems had been placed at nursing stations and in individual patients rooms. Total needle sticks in staff nurses reported during the 3 years (20.5%, 23.2%, 21.8%, not significant) did not decrease in the last 2 years. Simultaneously, hospital purchases of needle-containing devices increased 13.5%. Thus a constant reported needle-stick incidence rate may paradoxically represent a modest preventive effect of a hospital sharps-disposal system. PMID- 1593296 TI - Follow-up study among model and pattern makers in an automobile company in the Federal Republic of Germany. AB - The follow-up of a cohort of 528 model makers and a control group of 2273 tool makers shows an unusual pattern of mortality in the model makers' cohort. In contrast to the usual ranking, malignant neoplasms are the most frequent group of cause of death followed by diseases of the cardiovascular system. The rate ratio (RR) for malignant tumors is significantly increased among model makers compared with tool makers RR = 1.8, (95% confidence level [CL] = 1.3-2.7). The sites affected by excess cancer were stomach, the genitourinary organs, and the brain. In contrast to other studies, no tumors of the large intestine have been observed. Furthermore, there is a remarkable underrepresentation of tumors of the respiratory organs. Because these results are based on a rather small number of cases, further follow-up of the cohort is warranted to draw more profound conclusions. PMID- 1593297 TI - Spirometry in the occupational setting. Notes for guidance. PMID- 1593298 TI - Acquired dyschromatopsia: some comments concerning the procedure of testing and interpretation. PMID- 1593299 TI - The J-shaped curve in elderly hypertensives. AB - PURPOSE: To review the relationship between mortality and morbidity and achieved blood pressure, after drug treatment in elderly hypertensive patients. CONTENTS: Recent studies have suggested that a reduction in systolic blood pressure, with drug treatment, to levels below about 140 mmHg in elderly patients (greater than 60 years) may increase the risk of stroke. However, a J-shaped relationship between both mortality and morbidity and blood pressure has been reported in the untreated controls of the Hypertension in Elderly Patients in primary care (HEP) study. In the European Working Party on High Blood Pressure in the Elderly trial (EWPHE) there was a U-shaped relationship between total mortality and treated systolic pressure, but a similar U-shaped relationship was observed with diastolic pressure in patients on placebo. In addition, patients with the lowest pressure during treatment showed the greatest falls in body weight and haemoglobin concentrations, suggesting that the increased mortality seen with lower blood pressure levels may have been an expression of a deterioration in general health. Moreover, a U-shaped relationship between blood pressure and mortality has been observed in the very old (aged 80 + years). CONCLUSIONS: While it is premature to conclude, on the basis of present evidence, that reducing blood pressure to the lower part of the normal range is harmful in older patients, it appears prudent, nonetheless, not to lower blood pressure excessively with treatment in this age group. PMID- 1593300 TI - Age and blood-pressure-related changes in left ventricular diastolic filling. AB - PURPOSE: To evaluate the influence of different clinical and echocardiographic parameters on left ventricular diastolic filling in 66 mild to moderate hypertensives and 49 normotensives. METHODS: All subjects underwent an echocardiographic study with a pulsed Doppler evaluation of left ventricular filling. The hypertensive subjects also underwent non-invasive 24-h blood pressure monitoring. RESULTS: The ratio of early to atrial peak diastolic filling velocity and the ratio of the corresponding areas under the curve (AUC) were significantly lower in the hypertensives compared with the normotensives (P less than 0.001). In the hypertensives, office blood pressure, average 24-h mean blood pressure, the left atrial dimension and the left ventricular mass index were each related both to age and to diastolic filling. The variable most closely related to diastolic filling independently of age and the R-R interval was 24-h blood pressure (ratio of early: atrial peak filling velocity versus 24-h blood pressure: r = -0.307, P less than 0.05; ratio of early: atrial AUC versus 24-h blood pressure: r = -0.261, P less than 0.05). When the normotensives and hypertensives were each grouped according to age less than or equal to or greater than 40 years, the normotensive-hypertensive mean difference was greater in the subjects aged greater than 40 years for both the early:atrial maximal velocity ratio and the early:atrial AUC ratio. CONCLUSIONS: Age is the strongest clinical correlate for left ventricular diastolic function indices, in both hypertensives and normotensives. In the present study, average 24-h blood pressure and, to a lesser extent, the heart rate were also associated with an impaired diastolic performance. PMID- 1593301 TI - Senile hypertension and cognitive impairment: an overview. AB - PURPOSE: Both hypertension and cognitive impairment are common disorders in old people. This paper reviews epidemiological, clinical and experimental studies that have examined the association between these conditions. CONTENTS: Evidence is presented which suggests that raised blood pressure levels contribute to cognitive impairment in susceptible people, particularly those with concomitant conditions which predispose them to cerebral ischemia. Some studies have demonstrated that certain classes of antihypertensive drugs may have beneficial actions on ischaemic and cell growth processes, while others may tend to impair cognitive function, either by central actions or by alterations to cerebral blood flow. CONCLUSIONS: A successful approach to the treatment of hypertension associated cognitive impairment is likely to follow a detailed analysis of risk factors in the individual patient. Fundamental epidemiological work is required to clarify genetic components or risk, and more long-term treatment trials would also be helpful, although these have proved problematic in the elderly. At present, although it is clear that old people with hypertension should be treated, whether or not they are also cognitively impaired, further studies are necessary to decide on the best antihypertensive therapy for this substantial population. PMID- 1593302 TI - Endothelium and atherosclerosis. AB - PURPOSE: To review the effect of damaged endothelium on the development of atherosclerotic disease. BACKGROUND: Atherosclerotic cardiovascular disease is a complex problem involving lipid deposition, blood pressure, rheologic forces, carbohydrate tolerance and thrombogenic factors. The loss of functional, if not structural, integrity of the vascular endothelium is closely related to the initiation of atherosclerosis. The endothelium contributes to local vascular regulation. Normal endothelial cells are thrombo-resistant; they prevent leukocyte adhesion and control vascular tone by converting angiotensin I into angiotensin II, inactivating bradykinin, norepinephrine, serotonin and ADP, and by secreting vasodilator substances, such as prostacyclin and endothelium-derived relaxing factor (EDRF), and contracting factors such as endothelin. Endothelin is a potent vasoconstrictor peptide that increases intracellular calcium, causing a rapid and transient increase in c-fos and c-myc messenger (m)RNA levels and DNA synthesis in rat vascular smooth muscle cells. In isolated vessel segments, altered endothelial vasoreactivity is usually demonstrated following mechanical trauma to the endothelium. METHODS AND RESULTS: We investigated the function of normal and damaged endothelium in pigs, following superficial balloon injury, which produces a significant alteration in endothelium-dependent coronary vasoreactivity. The anesthetized pigs were given an intracoronary (left anterior descending artery) infusion of acetylcholine. The balloon injury caused a local transient spasm while the distal uninjured vessel did not change. When acetylcholine was given before the balloon injury, the diameter of the left anterior descending artery did not change, even after preconstriction in vivo with prostaglandin (PG) F2 alpha, but acetylcholine given after the balloon angioplasty caused dose-dependent vasoconstriction. It is known that vasoconstriction in arteries can reduce blood flow and increase arterial wall shear forces, which increase platelet deposition in injured arteries and may precipitate rupture of atherosclerotic plaques. CONCLUSION: The intact endothelium is one of the greatest sources of protection from arterial thrombosis, atherosclerosis and vasoconstriction. PMID- 1593303 TI - Epidemiological aspects of cardiovascular disease in the elderly. AB - BACKGROUND: Cardiovascular disease is the leading cause of death in the elderly in industrialized societies. However, in the elderly, unlike middle-aged subjects, little attention has been paid to strategies for reducing morbidity and mortality from this disease. OBJECTIVES: To review studies of risk factors for cardiovascular diseases in the elderly and the evidence, if any, of risk factor modification. FINDINGS: Overall, the evidence suggests that the established risk factors for cardiovascular disease in middle-aged subjects persist into old age. Several studies have shown that serum cholesterol is positively associated with a risk of coronary heart disease. In the very elderly, U-shaped distributions have been reported for the relationship between cholesterol and total mortality, probably as a result of other confounding factors. At present there is little experimental evidence of benefits from lowering cholesterol in the elderly. In contrast, several randomly allocated, placebo-controlled trials have established the benefits of blood pressure reduction (systolic or diastolic) up to the age of 84 years. A high blood pressure in the very old probably remains a risk factor, but prospective studies have reported non-linear relationships. Smoking has been reported to be a risk factor in the elderly in some, but not all studies. CONCLUSIONS: At present, only the treatment of high blood pressure can be definitively recommended in the elderly. The effects of both dietary and pharmacological modification of cholesterol need to be investigated. PMID- 1593304 TI - The effects of sodium depletion on ambulatory blood pressure and heart rate monitoring in the elderly. AB - OBJECTIVE: Old age is associated with impairment of the normal homeostatic response to cardiovascular stress. The purpose of our study was to determine whether a physiologic stress, such as sodium depletion, produces different, age dependent effects on the blood pressure and heart rate profile in old and young subjects. DESIGN: Blood pressure and the heart rate were studied in 11 young (age 28.7 +/- 3.1 years) and 14 elderly (76.1 +/- 3.4 years) male healthy volunteers, during ambulatory blood pressure monitoring and during postural stress before and after 2 days of sodium depletion. METHODS: Twenty-four-hour blood pressure monitoring was performed with a non-invasive automatic portable monitoring device. The postural evaluation consisted of a standard passive upright-tilt test to 70 degrees. Sodium depletion was obtained with a low-salt diet and diuretic treatment (100 mg hydrochlorothiazide) for 2 days. RESULTS: After sodium depletion no changes were found in the average blood pressure. The postural evaluation showed a fall in systolic blood pressure only in the elderly. The heart rate increased only in the young group, both during the ambulatory blood pressure monitoring and after the upright tilt. CONCLUSIONS: These results suggest that cardiovascular reserve is decreased in the elderly under a stress condition such as sodium depletion; this phenomenon may be linked to a blunted baroreceptor reflex response. PMID- 1593305 TI - Lipid metabolism and cardiovascular risk: should hypercholesterolemia be treated in the elderly? AB - PURPOSE: It is not clear whether an elevated serum cholesterol level is as important a risk factor for coronary heart disease in the elderly as it is in middle-aged men. This review highlights some aspects of this issue. OBSERVATIONAL STUDIES: The Framingham study showed that after the age of 65 years, serum cholesterol levels are associated with coronary heart disease only in women. The Honolulu (Hawaii) Heart Program, however, found that the same association also occurred in men aged over 65 years. INTERVENTION STUDIES: The Lipid Research Clinics trial and the Helsinki Heart Study both aimed to reduce coronary heart disease mortality by a drug-induced reduction in serum cholesterol levels. Each produced a significant reduction in coronary morbidity and mortality, of 20 and 30%, respectively, but failed to reduce total mortality significantly. Moreover, an increase in violent death (accident or suicide) was reported by the Helsinki study. LENGTH OF SURVIVAL AND CANCER MORTALITY: Elderly patients with moderate hypercholesterolemia have been reported to survive longer than those with a lower cholesterol level. Further, a significant increase in the cancer mortality rate has been observed in hypocholesterolemic subjects. These data have aroused concern about reducing serum cholesterol levels in patients aged over 65 years. CONCLUSIONS: At present, it seems that a moderate reduction of elevated serum cholesterol levels in elderly patients at risk of coronary heart disease may reduce the incidence of this disease and improve the quality of life in the elderly. The proposal needs to be tested by a randomly allocated controlled trial. The longer survival of patients with moderate hypercholesterolemia and the increase in cancer mortality or violent death seen among hypercholesterolemic subjects need to be further evaluated. PMID- 1593306 TI - Nicardipine retard in the therapy of elderly diabetic hypertensives: final report of observational study. AB - OBJECTIVE: An uncontrolled multicentre study was carried out in 10 hospitals of the Marche Region of central Italy, to evaluate the efficacy and tolerability of 40 mg nicardipine retard in elderly hypertensive patients with diabetes mellitus type II. DESIGN: The study lasted 6 months, single-blind for the first 3 months and open thereafter. The blood pressure criteria were 165 mmHg systolic and/or 95 mmHg diastolic measured at least three times consecutively in untreated patients or after 10 days of drug washout. PATIENTS: All subjects had a proven diagnosis of diabetes mellitus type II and were greater than or equal to 65 years of age. RESULTS: After the first 14 days of active treatment with nicardipine [corrected] retard at 40 mg/day, supine systolic blood pressure had fallen to 164.3 +/- 12.7 mmHg and diastolic to 92.2 +/- 7.3 mmHg (P less than 0.001). This first phase normalized blood pressure in 41.1% of patients. In 58.9% of patients the dose was doubled because goal blood pressure had not been achieved. After 4 weeks of therapy, mean supine systolic/diastolic values had fallen to 156.5 +/- 11.0/88.5 +/- 6.8 mmHg (P less than 0.001), and the proportion of patients requiring 80 mg/day had risen to 63.2%, with only 36.8% able to continue on the single dose. In 24.2% of the patients, monotherapy at 80 mg/day was not sufficient to normalize blood pressure and a second associated drug (enalapril, 10 mg/day) was administered. The mean blood pressure decrease induced by therapy was statistically significant from the second week of treatment (P less than 0.001). No significant variation in metabolic parameters was recorded during treatment. CONCLUSIONS: Nicardipine [corrected] retard was effective and well tolerated in elderly subjects, both clinically and metabolically. PMID- 1593307 TI - Therapeutic management of elderly hypertensives with concomitant ischaemic heart disease. AB - CHARACTERISTICS OF ELDERLY HYPERTENSIVES: Hypertension is most prevalent in older patients and is associated with increasing morbidity and mortality with age. Elderly hypertensives often suffer from concomitant diseases, such as ischaemic heart disease, caused by age-induced modifications to the cardiovascular system, haemodynamic function and neurohormone activity. THERAPEUTIC MANAGEMENT: Therapeutic management of elderly hypertensives with concomitant ischaemic heart disease must take account of the pharmacodynamic and pharmacokinetic changes that occur in older subjects and drugs should be selected for their efficacy in both diseases. Since elderly subjects often metabolize drugs more slowly, this population is particularly susceptible to drug-drug interactions and pharmacologically induced side effects. CHOICE OF DRUGS: The present review outlines the usefulness of diuretics, beta-blockers, angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers in elderly hypertensives with ischaemic heart disease. PMID- 1593308 TI - Insulin resistance and essential hypertension: pathophysiologic and therapeutic implications. AB - PURPOSE: Essential hypertension is often accompanied by metabolic abnormalities, which commonly include insulin resistance. In this paper we review data on the effects of different antihypertensive drugs on insulin resistance. DATA ANALYSIS: A number of reports have described a frequent association between hyperinsulinemia, hypertension and obesity. In epidemiological surveys, increased insulin concentrations have been seen in hypertensives and have been correlated with cardiovascular risk. Although the impact of antihypertensive therapy on glucose and lipid metabolism has been widely studied, few researchers have investigated the effects of different antihypertensive drugs on insulin resistance. An analysis of available data from controlled studies has shown that the use of thiazides is correlated with a decrease in insulin sensitivity. Pollare and co-workers tested insulin sensitivity by using the glucose-clamp technique in hypertensive patients, and found a 21% decrease in insulin sensitivity during atenolol treatment. Similar findings have been described with metoprolol. In contrast, calcium antagonists do not alter insulin resistance and/or sensitivity. At present, angiotensin converting enzyme (ACE) inhibitors seem to be the only drugs able to improve insulin sensitivity. CONCLUSIONS: ACE inhibitors may improve insulin-dependent glucose uptake, thus leading to a reduction in insulin concentrations. Calcium antagonists appear to preserve insulin sensitivity. Since insulin resistance may be an additional risk factor for cerebral and vascular disease, these drugs may be particularly useful in insulin-resistant hypertensives. PMID- 1593309 TI - Tularemia pneumonia in Oklahoma, 1982-1987. AB - OBJECTIVE: We assessed the incidence, risk factors, and prognostic implications of tularemia pneumonia in Oklahoma from 1982 through 1987. DESIGN: We retrospectively reviewed all reported case-patients over the six-year period 1982 1987. SETTING: Department of Health in Oklahoma, where tularemia is known to be endemic. PATIENTS: Of 128 patients with tularemia who entered the study, 32 had pulmonary involvement. MAIN RESULTS: Compared to patients without pulmonary involvement, those with tularemia pneumonia were older (52 vs 32, p less than .0001), less likely to give a history of vector exposure (25% vs 7%, p less than .05), more likely to present with typhoidal illness (56% vs 15%, p less than .0001), hospitalized longer (11.6 vs 4.7 days, p less than .001), more likely to have a positive culture (9 vs 7, p less than .01), and more likely to die (4 vs 1, p less than .01). CONCLUSIONS: Patients with tularemia pneumonia often present without historical or physical examination findings that suggest the diagnosis; thus, tularemia pneumonia often cannot be distinguished from other cases of community-acquired pneumonia. Therefore, especially in areas where the disease is endemic, tularemia must be considered in patients with pneumonia. PMID- 1593310 TI - Physician census and geographic distribution in Oklahoma from 1984 to 1990. PMID- 1593311 TI - Leaders in medicine: Robert G. Tompkins, MD. PMID- 1593312 TI - AIDS commentary and editorial shock infectious disease specialist. PMID- 1593314 TI - Experience with rigid fixation of mandibular fractures and immediate function. AB - The results of using rigid fixation for 75 mandibular fractures in 52 patients and allowing immediate function were retrospectively analyzed. Sixteen percent of fractures developed postoperative infection. All infections were in fractures associated with teeth; none occurred in fractures fixed within 24 hours of injury. Angle and posterior body fractures were most likely to become infected. Fractures with improperly applied rigid fixation also were subject to a high infection rate. It was unusual for infection involving this type of treatment to prolong the course of therapy or affect the final outcome. PMID- 1593313 TI - Rigid fixation in reconstruction of craniofacial fractures. AB - Ninety-four patients had either isolated fractures of the skull or midface, or combined fractures of the skull, periorbit, and/or midface. Thirty-five of these patients were treated by conventional methods, including maxillomandibular fixation (MMF) 4 to 6 weeks postoperatively, wire osteosynthesis, suspension ligatures, or a head frame. The remaining 59 patients were treated with either mini-, low-profile, micro-, or 3-D titanium plate fixation (rigid internal fixation [RIF]) and comprise the patient population for this study. Of the 59 patients, 11 were female and 48 male, ranging in age from 6 to 85 years, with a mean age of 34 years. Six patients had isolated skull fractures, 9 had combined skull and periorbital fractures, 31 had isolated midface fractures, and 13 patients had combined skull and midface fractures. The follow-up period ranged from 3 to 48 months. Patients with midface fractures were placed in MMF intraoperatively, and MMF was released at the completion of the procedure. At 2 to 4 days postoperatively, the occlusion was evaluated. Fifteen of the 38 dentate patients with either midface or combined skull and midface fractures were without MMF postoperatively. Twenty-three patients showed slight occlusal discrepancies and were treated with elastic MMF for 3 to 28 days (mean, 10 days). All reductions were judged to be stable throughout the postoperative course. Based on the results, use of RIF is recommended for primary reconstruction in craniofacial trauma patients whenever possible, thereby achieving three-dimensional stability, sufficient functional and cosmetic results, and often avoiding or reducing the need for MMF. PMID- 1593315 TI - Accuracy of face-bow transfer: effect on surgical prediction and postsurgical result. AB - One of the most common errors in model surgery for orthognathic surgery is in the mounting of the models on the articulator. This study assessed the ability of one type of face-bow to transfer the maxillary model to the articulator. Twenty-five consecutive mountings were evaluated by calculating the angle made between the maxillary occlusal plane on the cephalogram and comparing it with the maxillary occlusal plane angle on the articulator. An accurate face-bow transfer should transfer this angle, making the two similar. It was found that a significant difference between the maxillary occlusal plane angle on the cephalogram and the articulator was found in the average case. The implications of such errors and a technique to avoid them are presented. PMID- 1593316 TI - Arthroscopic disc repositioning and suturing: a preliminary report. AB - Eight patients (11 joints) underwent arthroscopic disc repositioning and suturing. Disc displacement was established by physical examination, magnetic resonance imaging (MRI), and diagnostic arthroscopy. Postoperative MRIs were taken at varying intervals between 1 day and 6 months. In all 11 joints, either partial improvement or normal disc position was observed arthroscopically. In 9 of the 11 joints, either partial improvement or normal position was observed on the postoperative MRIs. It is concluded that posterior disc repositioning and suturing is an achievable goal of temporomandibular joint arthroscopy. PMID- 1593317 TI - Electrophysiological assessment of human inferior alveolar nerve function. AB - This study describes a technique for making electrophysiological recordings from the inferior alveolar nerve of conscious human subjects. Recordings were obtained from 6 of 10 subjects, with consistent waveform latencies and amplitudes across subjects. The neurogenic origin of the responses was verified by blocking the nerve with 2% xylocaine, resulting in a loss of the waveform. The method is relatively simple, tolerated well by patients, and yields consistent electrophysiological information. Proposed refinements of the technique could result in a clinically useful method of objectively assessing the functional state of the inferior alveolar nerve following injury or surgical intervention. PMID- 1593318 TI - Changing trends with mandibular fractures: a review of 1,067 cases. AB - To evaluate current trends in facial trauma, records from 1,067 patients sustaining 1,515 mandibular fractures from 1979 to 1989 were reviewed. The greatest number of fractures occurred between the ages of 20 to 29 years. Sex distribution was approximately three males to one female. Altercations were found to have caused about half of the fractures, and motor vehicle accidents accounted for nearly one-third. Angle fractures were most common, constituting 26.7% of the total. The most common site of mandibular fracture resulting from altercation was the angle (39.1%); condylar, symphysis, and alveolar fractures less commonly resulted from altercations than from motorcycle and automobile accidents. PMID- 1593319 TI - The effect of treatment on facial attractiveness. AB - Pretreatment and posttreatment frontal and profile slides of 13 orthodontic camouflage and 13 orthognathic surgery patients were shown to three panels of judges: an orthodontic, an oral surgery, and a "lay" panel of first-semester dental students. Each judge rated the facial attractiveness of the pretreatment and posttreatment views of each patient using a visual analog scale. A mean pretreatment and posttreatment score was then calculated for each treatment group for each judge. Paired t tests were used to compare the treatment groups and time periods. The orthodontic camouflage group was rated as significantly more attractive than the orthognathic surgery patients before treatment. There was no significant change in the facial attractiveness mean score for the orthodontic group, whereas the orthognathic surgery group was rated as showing a significant improvement. However, the orthognathic surgery group was still rated as being significantly less attractive after treatment than the orthodontics-only group. PMID- 1593320 TI - Polymorphous low-grade adenocarcinoma of the oral cavity: a report of 14 cases. AB - The clinicopathologic characteristics of 14 new cases of low-grade polymorphous adenocarcinoma of the oral cavity are presented. Tumors were located in the palate in 10 cases, and in one case each in the base of the tongue, buccal mucosa, tonsil, and retromolar pad. Nine cases were previously diagnosed as other categories of benign and malignant tumors. The tumors were classified as terminal duct and low-grade papillary adenocarcinomas. Three cases developed local recurrence and four cases had lymph nodes metastasis, two on admission and two during the course of the disease. Two of the local recurrences and all cases with metastasis were salvaged with further surgery with or without irradiation. Recurrence and metastasis occurred only with the terminal duct adenocarcinoma. There was no death related to the neoplasm, although one patient is living with advanced disease. PMID- 1593321 TI - Training of the oral and maxillofacial surgeon in implantology. AB - This article reports the results of a survey of oral and maxillofacial surgery residency programs regarding the teaching of implantology. The findings show that although oral and maxillofacial surgery residents receive as much or more didactic training than most trainees in other dental specialties, and much more extensive surgical experience, the teaching is not uniform and there is still need for improvement in some areas. PMID- 1593322 TI - Biomechanical validation of the solitary lag screw technique for reducing mandibular angle fractures. AB - The purpose of this study was to determine whether the solitary lag screw technique meets the biomechanical demands of angle fractures. Simulated angle fractures in four cadaveric mandibles were reduced using solitary lag screws and the load-displacement relationships determined under functional loading of the individual mandibles. Subsequently, an angle fracture in a photoelastic mandible analog was fixed with a lag screw and subjected to similar loading. The mechanisms by which the solitary lag screw transferred functional loading were observed and recorded in a circular polariscope. Concomitant distraction tendencies were monitored and measured using displacement transducers. Correlation of the force-displacement measurements to photoelastic observation substantiated that the solitary lag screw functions as a tension band to provide a sufficient degree of interfragmentary compression and stability to withstand functional loading of the mandible. PMID- 1593323 TI - Osseous regeneration in the presence of four common hemostatic agents. AB - The iliac crest is a common site for bone procurement in oral and maxillofacial surgery. The goal of this study was to evaluate the potential for bone regeneration in the presence of four common hemostatic agents in a manner that parallels iliac bone procurement in humans. The agents evaluated were 1) Avitene (microfibrillar collagen; Medchem Products, Inc, Woburn, MA); 2) bone wax (beeswax with isopropyl palmitate; Ethicon, Inc, Somerville, NJ); 3) Gelfoam (absorbable gelatin sponge; The Upjohn Company, Kalamazoo, MI); and 4) Surgicel (oxidized regenerated cellulose; Johnson & Johnson Products, Inc, Patient Care Division, New Brunswick, NJ). Five surgical defects in each of four dogs were created for placement of the four materials; one defect served as an empty control site. The dogs were then allowed to heal over a 2-month period. Radiographic and histologic examination showed new bone formation in the presence of Avitene, Surgicel, and Gelfoam. Residual material incorporated in bone, without foreign-body response, was noted in the Avitene and Gelfoam sites. Bone wax, however, showed an intense foreign-body reaction, characterized by giant cells, plasma cells, fibrous granulation tissue, and lack of bone reformation. On the basis of these initial findings, it was concluded that Surgicel, Avitene, and Gelfoam may be adequate hemostatic agents for use in iliac bone procurement, whereas the use of bone wax appears to be contraindicated. PMID- 1593324 TI - Bone hole diameter as a function of drill guide length and drilling method in rigid internal fixation. AB - This study examines drill guide length and drilling method to see which technique produces the most accurate hole diameter. Two hundred twenty-five holes were produced in fresh porcine mandibles and then measured with a micrometer. A long guide, a short guide, and no guide were used with a drill press, a pneumatic drill, and a manual drill. Using a 2-mm drill bit, the overall average diameter was 2.03 mm and the overall range was 1.85 mm to 2.60 mm. Statistical analysis of the data indicates the drilling method and the guide length made no difference in the hole diameter at the 95% level (P = .05). PMID- 1593325 TI - Diagnosis of medial temporomandibular joint disc displacement with dual space anteroposterior arthrotomography: correlation with cryosectional morphology. AB - This study was undertaken to determine if it is possible to identify medial disc displacement with dual space anteroposterior (AP) arthrotomography. Contrast medium was injected into the upper and lower joint spaces of 11 fresh temporomandibular joint (TMJ) autopsy specimens and arthrotomograms were obtained with an AP projection. The arthrotomograms of five joints showed an enlargement of the medial recess of the upper joint compartment with folding of the disc inferiorly. This was interpreted as an indication of medial disc displacement. Cryosections confirmed medial displacement of the disc in these five joints and showed a slight medial displacement of a disc in one additional joint. Retrospective evaluation of the arthrotomogram of this joint showed that the disc was slightly medially displaced, but without folding. The results of this study suggest that AP dual space arthrotomography can be useful for the diagnosis of medial disc displacement in cadaver material. PMID- 1593326 TI - Magnetic resonance imaging in the diagnosis of trigeminal neuralgia. AB - Trigeminal neuralgia is not a specific disease, but a symptom elicited by pathology involving the fifth cranial nerve. Advances in the field of magnetic resonance imaging (MRI) have made this the premier imaging modality in the diagnostic workup of trigeminal neuralgia. This article reviews the pertinent anatomy of the trigeminal nerve as well as the structural lesions that produce the symptoms of the condition. The advantages of MRI over other imaging methods are outlined, and the indications for obtaining this study are discussed. PMID- 1593327 TI - Expansile mass of the body of the mandible. PMID- 1593328 TI - Pica and iron-deficiency anemia: a case report. PMID- 1593329 TI - Gigantic osteoma of the mandible: report of a case. AB - A case of a very large solitary osteoma of the right posterior mandible in a 22 year-old man is presented. The tumor was asymptomatic despite its location and large size. It was removed via an extraoral Risdon approach without complication. The importance of differentiating a large solitary osteoma from a parosteal osteogenic sarcoma is emphasized. Any patient presenting with a solitary osteoma also should be evaluated for Gardner's syndrome. PMID- 1593330 TI - Toxic epidermal necrolysis: report of a case. PMID- 1593331 TI - Discoid lupus erythematosus of the lip and face. PMID- 1593332 TI - Disinhibition of behaviors with midazolam: report of a case. PMID- 1593333 TI - Cervicofacial actinomycoses following sagittal split ramus osteotomy: a case report. PMID- 1593334 TI - Nasal splint construction from light-cured resin. PMID- 1593335 TI - Treatment of orofacial vascular lesions. PMID- 1593336 TI - Diagnosing the Muir-Torre syndrome. PMID- 1593337 TI - Accuracy and reliability of glucose reflectance meters in the high-risk neonate. PMID- 1593338 TI - Changing face of academic pediatrics. PMID- 1593339 TI - Changing face of academic pediatrics. PMID- 1593340 TI - Changing face of academic pediatrics. PMID- 1593341 TI - Treatment of persistent pulmonary hypertension in the neonate. PMID- 1593342 TI - Osteosclerosis versus osteopetrosis of the newborn. PMID- 1593343 TI - Resurgence of tuberculosis in children. PMID- 1593344 TI - Maternal vitamin levels during pregnancies producing infants with neural tube defects. AB - Women at very high risk for having a child with a neural tube defect (NTD) because they had previously delivered affected children significantly reduced their recurrence rate by taking folate supplements before conception. To clarify how these results might apply to a lower-risk general obstetric population, we measured folate, vitamin B12, and retinol levels in maternal serum drawn early in 89 pregnancies resulting in NTD offspring and 178 control pregnancies identified from the Finnish Registry of Congenital Malformations. In 86.5% of the subjects, specimens were collected within 8 weeks after neural tube closure. In the NTD case mothers the mean (+/- SD) levels were not significantly lower than in control mothers: folate, 4.13 +/- 2.36 versus 4.28 +/- 2.52 ng/ml; vitamin B12, 482.8 +/- 161.1 versus 520.3 +/- 191.9 pg/ml; and retinol, 51.2 +/- 17.0 versus 50.5 +/- 16.9 micrograms/dl. After adjustment for age of the specimen, gestational age at which the specimen was drawn, maternal age, and maternal employment status, the odds ratios for being a case mother were 1.00 (95% confidence interval (CI) 0.91 to 1.10) for folate, 1.05 (95% CI 0.92 to 1.19) for vitamin B12, and 0.99 (95% CI 0.88 to 1.10) for retinol. Excluding NTD cases with known or suspected causes unrelated to vitamins, restricting the analyses to interviewed subjects, and excluding subjects whose specimens were collected after 15 gestational weeks confirmed that NTD case and control vitamin levels did not differ significantly. This population-based investigation in a low rate area demonstrated no relationship between maternal serum folate, vitamin B12, or retinol levels during pregnancy and the risk of NTDs. PMID- 1593345 TI - Comparison of the vaginal flora in sexually abused and nonabused girls. AB - The presence of sexually transmitted pathogens in the vagina of the sexually abused girl may provide direct evidence of sexual abuse; the presence of other abnormal vaginal organisms may provide indirect evidence of abuse. To identify abnormal vaginal organisms, we prospectively studied the flora of 209 sexually abused girls (cases) and compared it with that in a concurrent control group of 108 girls. Case and control subjects were from the same community, were predominantly white, and 71% of each group were 3 to 10 years of age. The sexually transmitted pathogens (Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, herpes simplex virus) were isolated exclusively from the case group at a low frequency (less than 1%). The isolation of Mycoplasma species exclusively in the case group (4%), and of Gardnerella vaginalis in 7% of the case group versus 1% of the control group, suggests that both these organisms may be sexually transmitted. Other bacteria also were collectively more frequent in the case group (16% vs 6%). There may be an association between sexual activity and colonization of the lower genital tract in young girls. PMID- 1593346 TI - Egg hypersensitivity and adverse reactions to measles, mumps, and rubella vaccine. AB - We evaluated the safety of the measles-mumps-rubella (MMR) combination vaccine in 140 children with egg hypersensitivity. All children, regardless of vaccine skin test results or severity of egg hypersensitivity, were safely immunized with the MMR vaccine. Systemic reactions to MMR vaccine in two nonallergic children were documented, indicating that reactions unrelated to egg protein can occur. With the use of a competitive enzyme-linked immunosorbent assay, the standard MMR injection was found to contain approximately 37 pg of ovalbumin-like material. This study provides 95% confidence that at least 97.5% of egg-allergic children will tolerate MMR vaccine without significant difficulty. Skin testing was not found to be helpful in predicting an adverse reaction. We recommend that the American Academy of Pediatrics consider revising its current policy regarding skin test response to MMR vaccine and administration of MMR vaccine to egg allergic children. PMID- 1593347 TI - Neurologic events after partial exchange transfusion for priapism in sickle cell disease. AB - We describe six boys with homozygous sickle cell disease, aged 7 to 13 years, in whom acute, severe neurologic abnormalities developed 1 to 11 days after partial exchange transfusion was performed to treat priapism that was unresponsive to more conservative therapy. Hemoglobin levels were 10.5 to 13.4 gm/dl (mean 12.1 gm/dl), and hemoglobin S levels were 18% to 33% (mean 27%) before the onset of neurologic complications. Severe headache was the initial finding in five patients, four of whom had increased intracranial pressure and three of whom required tracheal intubation and hyperventilation. Four patients had seizures; three had focal neurologic deficits for more than 24 hours. Cerebral arteriography demonstrated vascular abnormalities, including irregularity, stenosis, and complete occlusion of vessels. Patients treated with regular erythrocyte transfusions had no recurrence of neurologic signs or symptoms when hemoglobin S levels were kept at 30% to 50%. The occurrence of serious neurologic complications after partial exchange transfusion in patients with homozygous sickle cell disease from three centers indicates the possibility of a causal relationship between the events. Early and thorough investigation of neurologic symptoms, especially severe headache, is warranted in this clinical setting. PMID- 1593348 TI - Magnetic resonance imaging in the diagnosis of growth hormone deficiency. AB - Forty-six patients with idiopathic growth hormone deficiency were examined by magnetic resonance imaging at a mean (+/- SEM) age of 9 +/- 1 years (range 15 days to 20 years). They were classified into two groups according to MRI images: group 1 (n = 29) had pituitary stalk interruption syndrome and group 2 (n = 17) had normal pituitary anatomy. All patients with pituitary stalk interruption had a pituitary height at less than -2 SD for age; three had no visible anterior pituitary lobe. By contrast, the pituitary height was less than normal in only 10 patients (60%) with normal pituitary anatomy. Growth hormone deficiency was transient in one of the seven patients with normal pituitary anatomy and height. The group with pituitary stalk interruption had the first symptom of growth hormone deficiency at an earlier age (2.8 +/- 0.6 vs 5.5 +/- 1.2 years; p less than 0.001), were of smaller stature (-4 +/- 0.2 vs -3 +/- 0.2 SD; p less than 0.01) and had lower GH peak response to provocative testing (3 +/- 0.4 vs 5 +/- 0.5 ng/ml; p less than 0.001) than did the group with normal pituitary anatomy. Their pituitary gland was also shorter (2.5 +/- 0.2 vs 3.5 +/- 0.2 mm; p less than 0.01). All the patients with multiple pituitary deficiencies except one (n = 19) belonged to this group. One girl with pituitary stalk interruption and deficiencies in growth hormone and thyroid-stimulating hormone had advanced central precocious puberty. We conclude that the evaluation of the shape and height of the pituitary gland by MRI is an additional tool for the diagnosis of growth hormone deficiency. The presence of pituitary stalk interruption confirms this diagnosis and is predictive of multiple anterior pituitary deficiencies. The lack of a significant increase in perinatal abnormalities in this group and the association of pituitary stalk interruption with microphallus and with facial or sella abnormalities suggest that this appearance may have an early antenatal origin. The finding of a familial case of pituitary stalk interruption suggests a genetic origin. PMID- 1593349 TI - Treatment of children with homozygous familial hypercholesterolemia: safety and efficacy of low-density lipoprotein apheresis. AB - We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p less than 0.01) and preapheresis LDL-cholesterol values (r = 0.61; p less than 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death. PMID- 1593350 TI - Giant pigmented nevi: clinical, histopathologic, and therapeutic considerations. AB - Eighty pediatric patients with giant pigmented nevi more than 20 cm in their greatest diameter are reported. The incidence was 1 in 4150 general pediatric outpatients. The mode of inheritance of giant pigmented nevi is probably multifactorial; four second-degree relatives of our patients also had large nevi, and there was a 2:1 female predominance. Satellite nevi were present in 74% and nevi in mucous membranes in 31% of the patients. Eighty-six percent of nevi were pigmented and hairy. Benign nodules were observed in 19% of the patients and plexiform overgrowths in 6%. Nevi extensively involving the extremities resulted in reduced growth of the affected limb. Electroencephalograms showed abnormalities in 20% of the patients with giant pigmented nevi involving the head and upper portion of the trunk. Malignant transformation appeared in four patients and was fatal in three of them. Management consisted of observation only in 49%, surgery in 27.5%, chemical peel in 21%, and dermabrasion in 2.5% of the patients. The mean follow-up was 4.7 years. PMID- 1593351 TI - Prevention of neural tube defects. PMID- 1593352 TI - Serum antibodies against a 69-kilodalton outer-membrane protein, pertactin, from Bordetella pertussis in nonvaccinated children with and without a history of clinical pertussis. AB - Serum antibodies against pertactin were found in all samples from 260 nonvaccinated healthy Swedish 1- to 4-year-old children, although 42% had neither a history of clinical pertussis nor antibodies against pertussis toxin or filamentous hemagglutinin. Pertactin antibody levels were, however, higher in children with a history of pertussis than in those without a history of pertussis, and higher in children with antibodies against pertussis toxin and filamentous hemagglutinin than in those without such antibodies. PMID- 1593353 TI - Immune hemolysis, disseminated intravascular coagulation, and serum sickness after large doses of immune globulin given intravenously for Kawasaki disease. AB - One week after treatment with intravenously administered immune globulin and aspirin, a child with Kawasaki disease had persistent fever and an increase in coronary artery diameter to greater than 3 mm. Two additional doses of immune globulin were given intravenously. Rapid hemolysis occurred, followed by disseminated intravascular coagulation and serum sickness. Clinicians should be aware that immune globulin preparations contain antibodies to blood-type antigens that may cause significant hemolysis and disseminated intravascular coagulation. PMID- 1593354 TI - Pituitary gigantism caused by growth hormone excess from infancy. AB - A 2 1/4-year-old boy with pituitary gigantism had a large pituitary macroadenoma. Gross tumor removal has prevented further visual losses, but he has had persistent hypersecretion of growth hormone and prolactin. Treatment with somatostatin analog has decreased both hormone secretion and growth velocity. PMID- 1593355 TI - Cobalamin C defect associated with hemolytic-uremic syndrome. AB - We describe a female infant with typical features of the cobalamin C form of combined methylmalonic aciduria and homocystinuria who also had the hemolytic uremic syndrome with thrombocytopenia, microangiopathic hemolytic anemia, hypertension, and renal failure. Review of this and other described cases of the cobalamin C defect suggests that the hemolytic-uremic syndrome is part of the phenotypic spectrum of this inborn error of cobalamin metabolism. PMID- 1593356 TI - Rate of bronchopulmonary dysplasia as a function of neonatal intensive care practices. AB - Some differences among neonatal intensive care units (NICUs) in incidence of bronchopulmonary dysplasia may reflect variations in medical care practices. After adjusting for differences in the inherent risk of bronchopulmonary dysplasia among 223 infants of less than 1751 gm birth weight who were admitted to three Harvard-affiliated NICUs, we used multivariate analysis to explore the extent to which medical care practices during the first days of life varied with the rate of bronchopulmonary dysplasia. In our analyses, variables were grouped by three major hypotheses: oxygen toxicity, barotrauma, and fluid overload. The NICU designated 1 (the one with the highest rate of bronchopulmonary dysplasia) used much higher than expected colloidal volumes during the first 4 days of life; in contrast, in the NICU designated 3 (the one with the lowest rate of bronchopulmonary dysplasia), infants consistently received lower than expected amounts of colloidal solution. Signs of patent ductus arteriosus were also much more frequent than expected during this time at NICU 1; rates were much lower than predicted at NICU 2 and were near predicted values at NICU 3. Maximum inspired oxygen fraction during the first 4 days varied significantly in a direction inconsistent with the oxygen toxicity hypothesis. Maximum arterial oxygen tension was significantly less than expected at the hospital with the lowest rate of bronchopulmonary dysplasia (NICU 3). None of six medical care practices indicating potential for barotrauma varied with NICU expect for positive end-expiratory pressure, which varied in a direction suggesting a protective effect against bronchopulmonary dysplasia. These findings agree best with the hypothesis that differences in hydration during the first days of life account for some of the difference among NICUs in bronchopulmonary dysplasia occurrence. PMID- 1593357 TI - Effect of early feeding on maturation of the preterm infant's small intestine. AB - To determine the response of the preterm infant's intestine to entire feedings at different postnatal ages, we recorded results of manometry of the gastroduodenum and determined fasting plasma concentrations of gastrin, gastric inhibitory peptide, neurotensin, and peptide YY three times in each of two groups: 27 preterm infants were randomly assigned to receive hypocaloric enteral nutrition on postnatal days 3 to 5 (early feeding) or on days 10 to 14 (late feeding). Initial observations (study 1) were performed by the fifth postnatal day; study 2 was performed on days 10 to 14, and study 3 on days 24 to 28. Early-fed infants received hypocaloric feedings immediately after study 1; late-fed infants did not receive enteral feedings until the completion of study 2. Although motor activity and fasting gastrointestinal peptide concentrations did not differ between groups at study 1, at study 2 early-fed infants had significantly more mature motor patterns than did babies not being fed. Early-fed infants also had significantly higher plasma concentrations of gastrin and gastric inhibitory peptide than did late-fed infants; neurotensin and peptide YY values were similar in both groups. By the time of study 3, when late-fed infants had also received enteral feedings, gut development was not different in the two groups. However, early-fed infants were able to tolerate full oral nutrition sooner, had fewer days of feeding intolerance, and had shorter hospital stays. Thus the provision of early hypocaloric nutrition was associated with earlier nutrition of preterm infants' intestinal function and resulted in improved feeding tolerance. These findings support the use of early feedings in preterm infants. PMID- 1593358 TI - Disparate black and white neonatal mortality rates among infants of normal birth weight in Chicago: a population study. AB - To determine the extent to which disparities in risk status and access to tertiary care affect racial differences in neonatal mortality rates among normal birth weight infants, we conducted a vital records study concerning normal weight black (N = 44,399) and white (N = 48,146) singleton births in Chicago. Neonatal mortality rate among black infants was twice that among white infants (3.3 deaths per 1000 births vs 1.5 deaths per 1000 births); the unadjusted black relative risk equaled 2.2 (95% confidence interval, 1.7 to 2.9). Because prematurity, growth retardation, congenital anomalies, low Apgar scores at 5 minutes, teenage mothers, and poverty were more common among black infants, multivariate analyses were performed. The disparity in mortality rate was greatest between black and white infants with none of these risk factors; relative risk for black infants equaled 3.6 (95% confidence interval, 2.0 to 6.7). Approximately 30% of all deaths of black infants were attributable to birth in nontertiary hospitals. When the confounding variables, including hospital of birth, were put into a multivariate logistic-regression model, the adjusted relative risk estimate (odds ratio) for black infants equaled 1.5 (95% confidence interval, 1.1 to 2.0). Traditional risk factors fail to explain the racial disparity in neonatal mortality rate among normal birth weight infants. Level of perinatal care available, or some factor closely related to this level, is an important determinant of neonatal chance of survival for normal birth weight urban black infants. PMID- 1593359 TI - Addition of metolazone to overcome tolerance to furosemide in infants with bronchopulmonary dysplasia. AB - A decreased response to the loop diuretic furosemide develops within a few doses in young infants. We tested the hypothesis that the use of the thiazide-like diuretic metolazone, in combination with furosemide, would inhibit water and electrolyte reabsorption and overcome pharmacologic tolerance to furosemide alone. Infants with bronchopulmonary dysplasia of similar gestational and postnatal ages were randomly assigned to one of three groups. Group 1 (n = 6) received furosemide (1 mg/kg per dose) intravenously every 24 hours for a total of five doses. Group 2 (n = 8) received the same treatment as group 1, but in addition metolazone (0.2 mg/kg per dose) was given enterally with doses 3 and 4 of furosemide. Group 3 (n = 8) received metolazone (0.2 mg/kg per dose) enterally every 24 hours for five doses. Urine was collected before the first diuretic dose and throughout the study for determination of the urine flow rate; urinary excretion of sodium, chloride, and potassium; and creatinine clearance. Urinary flow rate and urinary sodium and chloride excretion increased after the first dose in all groups. In the infants treated with either furosemide or metolazone, urinary flow rate and urinary and chloride excretion returned to baseline values after the last three doses. In contrast, when furosemide was administered with metolazone, urinary flow rate and urinary excretion of sodium, chloride, and potassium were greater than the values for baseline and for the previous dose, as well as for the corresponding doses of furosemide in group 1 and metolazone in group 3. Tolerance to furosemide (group 1) and metolazone (group 3) appeared to be explained by compensatory increased sodium and chloride reabsorption without changes in creatinine clearance. We conclude that the administration of metolazone with furosemide enhances diuresis, natriuresis, and chloruresis and overcomes the rapid development of tolerance to furosemide in infants with bronchopulmonary dysplasia by blocking the compensatory increase in renal sodium and chloride absorption. PMID- 1593360 TI - Dose-related bronchodilator response to aerosolized salbutamol (albuterol) in ventilator-dependent premature infants. AB - We used a placebo-controlled standardized protocol to define the dose-response relationship to the beta-adrenergic bronchodilator salbutamol (albuterol) in 10 ventilator-dependent premature infants at a postnatal age of 13.3 +/- 4.9 days. Passive respiratory system resistance and compliance were measured at baseline and 10 minutes after administration of salbutamol via a metered-dose inhaler and spacer device. Salbutamol caused a significant dose-related response with a 33% mean decrease in respiratory system resistance (p less than 0.05) and a 67% mean increase in respiratory system compliance (p less than 0.001). In seven and six patients, respectively, 100 micrograms of salbutamol caused significant improvement in resistance and compliance; 200 micrograms was required in the remainder, but one patient had no improvement in compliance. Oxygen saturation increased linearly with the increase in compliance. In 7 of the 10 infants, the duration of action of 200 micrograms of salbutamol on the following day was 3 hours. We conclude that bronchodilator treatment may be useful in the management of ventilator-dependent neonates with respiratory distress syndrome. PMID- 1593361 TI - Loracarbef (LY163892) versus amoxicillin-clavulanate in the treatment of bacterial acute otitis media with effusion. AB - The efficacy and safety of loracarbef, a new beta-lactam antibiotic, was compared with that of amoxicillin-clavulanate potassium in the treatment of bacterial acute otitis media with effusion. A double-blind format was utilized to administer 10-day, randomized, parallel treatment regimens to patients who were between 6 months and 12 years of age. The most prevalent causative pathogens found in the two treatment groups were Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis. The percentages of favorable posttherapy clinical responses in evaluable patients were similar for both drugs: 87.3% (124/142) of the loracarbef group, compared with 91.5% (130/142) of the amoxicillin-clavulanate group, showed favorable responses within 72 hours after treatment. Ten to sixteen days after treatment, 68.1% of the loracarbef group, compared with 76.1% of the amoxicillin-clavulanate group, showed favorable responses. More patients in the amoxicillin-clavulanate group reported treatment emergent events: 46.1% compared with 35.8% in the loracarbef group (p = 0.023). Diarrhea was the most frequently reported event, occurring in 13.3% of the loracarbef group and in 26.3% of the amoxicillin-clavulanate group (p less than 0.001). Vomiting was reported by 5.8% of the loracarbef group and 10.3% of the amoxicillin-clavulanate group (p = 0.072). Loracarbef is comparable in efficacy to amoxicillin-clavulanate in the treatment of bacterial acute otitis media with effusion and has a more desirable safety profile. PMID- 1593362 TI - Safety and pharmacokinetics of fluconazole in children with neoplastic diseases. AB - To evaluate the safety, tolerance, and pharmacokinetics of fluconazole in children with neoplastic diseases, we studied fluconazole in 26 children, aged 5 to 15 years, with normal renal function who were receiving treatment for cancer. The patients received fluconazole, 2, 4, or 8 mg/kg per day for 7 days intravenously for a 2-hour period. Patients had no nausea or vomiting related to fluconazole; three patients had an asymptomatic rise in hepatic aminotransferase values after four to six doses (one patient at 2 mg/kg per day and two patients at 8 mg/kg per day), which returned to normal within 2 weeks after discontinuation of the drug. Fluconazole showed linear first-order kinetics over the dosage range tested and during multiple dosing. After the first dose, mean clearance was 22.8 +/- 2.3 ml/min, volume of distribution 0.87 +/- 0.06 L/kg, and terminal elimination half-life 16.8 +/- 1.1 hours. Similarly, after the last dose, clearance was 19.4 +/- 1.3 ml/min, volume of distribution 0.84 +/- 0.04 L/kg, and terminal elimination half-life 18.1 +/- 1.2 hours. Patients receiving their first fluconazole dose of 8 mg/kg achieved peak serum levels of 9.5 +/- 0.4 microgram/ml and trough levels of 2.7 +/- 0.5 microgram/ml 24 hours later, and an area under the serum concentration-time curve from time zero to infinity of 186 +/- 16 micrograms.hr per milliliter. Renal clearance of fluconazole was 65% +/- 5% of total clearance and demonstrated the predominantly renal excretion of this drug. We suggest that the shorter serum half-life and the higher frequency of aminotransferase elevations in comparison with those of adults warrant careful investigation of fluconazole in controlled clinical trials. PMID- 1593363 TI - Unforgettable patients. PMID- 1593364 TI - Infection with Ehrlichia in childhood. PMID- 1593365 TI - Nutritional status and growth in children with chronic hepatitis B. AB - As reported for other chronic liver diseases, hepatitis B virus (HBV) chronic infection might result in malnutrition. In order to establish whether this disease could be responsible of malnutrition and hence influence growth, 75 children, chronically infected with HBV, have been followed up for 4 years. Thirty-one of them had chronic active hepatitis (CAH), 25 chronic persistent hepatitis (CPH), 14 chronic lobular hepatitis (CLH), and five cirrhosis (three active, two inactive). The nutritional status was evaluated every 12 months, with careful physical and laboratory examinations. General nutritional status was estimated according to Waterlow criteria (13, 14). At our first observation, 50 children were following a balanced diet with a caloric intake adequate for age and weight, whereas 25 were on a low-fat diet, begun in the belief of its therapeutic value. For seven patients of this second group, the caloric intake was below the daily requirement. The latter group showed a growth failure in weight when they were first seen at our center and gained weight when the dietary intake was normalized. However, no biochemical feature of malnutrition was observed in all the 75 children. At the end of the follow-up period, the nutritional status was satisfactory for all of them. PMID- 1593366 TI - Detection of hepatitis B virus DNA in the liver of children with chronic hepatitis B by in situ hybridization and its relation to other viral markers. AB - The aim of the study was to detect hepatitis B virus (HBV) DNA by in situ hybridization (ISH) with a 35S-labeled radioactive probe in frozen liver biopsy tissue sections of 63 hepatitis B virus surface antigen (HBsAg)-positive children. The results were compared to other markers of viral replication. HBV DNA was detected in 48 children. Of the 15 negative cases, four had hepatitis B envelope antigen (HBeAg), 10 anti-HBe, and one neither HBeAg nor anti-HBe. Free HBV DNA in serum and liver was positive in one patient. Forty of the positive children were HBeAg- and six anti-HBe-positive; two were negative for both. Of 45 36 had HBV DNA in serum. In 38 of 47 HBV DNA and in 31 of 42 HBcAg could be detected in the liver. The HBV DNA signals were located mainly over the cytoplasm of hepatocytes. The distribution of HBV DNA in the tissue was classified as homogeneous, inhomogeneous with focal patches, and focal. It is concluded that in situ hybridization is a reliable method for detection of HBV DNA in liver tissue of children with chronic hepatitis B. The technique, which can be applied to small amounts of liver tissue, provides informations about the distribution of replicative viral sequences, complementing laboratory data, liver histochemistry, and histology. PMID- 1593367 TI - Use of intravenous lipid and hyperbilirubinemia in the first week. AB - Serum triglycerides, free fatty acids, unconjugated bilirubin, and albumin were evaluated in 40 neonates receiving 0.5-3.5 g/kg/day of a 50/50 soybean-safflower lipid emulsion infused during 18 h. The purpose of the study was to evaluate lipid tolerance and unconjugated hyperbilirubinemia according to our total parenteral nutrition protocol, which initiates lipid on postnatal day 4. Mean serum triglycerides and free fatty acids were within the range of prelipid infusion values at all dosages, and no statistically significant differences were noted between very-low-birth-weight neonates and those greater than 1,500 g birth weight. Mean free fatty acid:albumin molar ratio was less than 1.0 at all dosages and no individual patient values exceeded a ratio of 3.0. Mean peak serum unconjugated bilirubin of 5.8 mg/dl on postnatal day 3 was stable or fell the next 10 days of lipid-inclusive total parenteral nutrition. Initiating intravenous lipid on the 4th postnatal day at 0.5 g/kg/day and increasing at 0.5 g/kg/day increments at the end of the 1st postnatal week appears to be tolerated well. However, 5% of serum triglyceride levels exceeded 200 mg/dl. Therefore, in view of the unpredictability of a given patient's tolerance to lipid infusion, there should be monitoring for lipemia. PMID- 1593368 TI - Influence of infant diets on the ecology of the intestinal tract of human flora associated mice. AB - The effect of diet on intestinal ecology was studied in germ-free mice that were inoculated orogastrically with predominant intestinal flora components isolated from the feces of breast-fed human infants. The flora components colonized the intestines of mice and persisted at fixed population levels. Groups of flora- associated mice were fed either human milk, bovine milk, whey-dominant formula, or formula modifications exclusively for 2 weeks, and then examined for changes in small intestinal and cecal flora composition, cecal pH, and resistance to intestinal colonization with Salmonella typhimurium. Dietary variations influenced the composition of the flora to a moderate degree but the differences were generally not statistically significant. However, the addition of bovine lactoferrin to the whey-dominant formula resulted in significantly greater counts of Bifidobacterium, Bacteroides, Enterococcus and total aerobes in the small intestine when compared with mice fed unsupplemented formula. Bifidobacterium was present in large numbers in both the ceca and small intestines of mice fed the lactoferrin-supplemented formula. Despite similarities in intestinal flora patterns among mice fed the various diets, human milk consumption resulted in a lower pH of cecal contents and a greater resistance to colonization by Salmonella typhimurium after orogastric challenge than the consumption of the other diets. PMID- 1593369 TI - Transient elevation of urinary catecholamine excretion and cholestatic liver disease in a neonate with hypopituitarism. AB - Hypothalamic hypopituitarism was diagnosed in a 3-month-old boy presenting with cholestatic liver disease, which resolved 5 weeks after the start of replacement therapy with hydrocortisone and human growth hormone. Clinical and pathohistological features of liver disease associated with neonatal hypopituitarism in this patient are compared to those of patients reviewed from the literature. Urinary excretion of dopa and 3-methoxytyramine but not of other catecholamine metabolites was elevated during cholestatic liver disease. 3 Methoxytyramine excretion normalized when cholestasis resolved. Altered hepatic metabolism of catecholamines due to growth hormone and cortisol deficiency may explain this observation. PMID- 1593370 TI - Pharmacokinetics and safety of a new solution of vitamin K1(20) in children with cholestasis. AB - In cholestatic diseases, the absorption of fat-soluble compounds, including vitamin K1(20), is low and periodic administration of vitamin K1(20) is often necessary. Due to the low absorption of vitamin K1(20) from the Konakion formulation, late hemorrhagic disease of the newborn also occurs especially after oral vitamin K1(20) prophylaxis with Konakion. We investigated the pharmacokinetics and the safety of a new formulation of vitamin K1(20) in a mixed micelles (MM) solution. Compared to the old formulation (Konakion) using Cremophor EL as a solubilizer, the higher vitamin K1(20) levels (as measured by HPLC) in serum obtained after oral administration of the MM formulation clearly demonstrate a superiority of this new formulation. Additionally, the elimination of Cremophor EL as well as of propylene glycol from the formulation avoids possible adverse effects associated with intravenous or intramuscular administration. Furthermore, in most cases, the discomfort of parenteral injections can be overcome by simple oral administration even in children with severe cholestasis. PMID- 1593371 TI - Effect of oral insulin on lactase activity, mRNA, and posttranscriptional processing in the newborn pig. AB - Insulin, found in human and pig colostrum and mature milk, appears to influence small intestinal growth and development. Ileal lactase activity is increased when porcine insulin is added to feedings administered to newborn piglets. We studied 2-day-old miniature piglets to determine whether the increase in lactase activity is accompanied by changes in enterocyte expression of lactase activity, steady state levels of lactase mRNA, and/or posttranscriptional changes in lactase processing. We randomized the piglets to receive bottle feedings of a swine weaning milk formula with (group F + I) or without (group F) the addition of 85 mU/ml of regular porcine insulin. The piglets were fed for 6 days (to 8 days of age), after which they were killed and the small intestine removed for analysis. Despite large differences between groups in enterocyte expression of lactase activity in the ileum, no differences were noted in the level of ileal lactase mRNA. The relative proportions of the 207, 210, and 230 kDa precursors of the 160 kDa mature lactase protein were similar between groups. These data indicate that the insulin-induced increased expression of ileal lactase activity is not regulated at the level of its mRNA or at the level of processing of the polypeptide. PMID- 1593372 TI - Use of ass' milk in multiple food allergy. AB - We report a study of realimentation techniques in 9 unweaned infants with multiple food hypersensitivity. The patients had presented severe symptoms of cow's milk allergy and successive attempts using milk containing soy protein and/or a semielemental formula in their alimentation did not improve their clinical condition, due to the onset of hypersensitivity to these allergens as well. After a short period of parenteral alimentation the infants were refed per os with ass' milk (250 ml/kg/day) + medium chain triglycerides (40 ml/L milk). This food was well tolerated by all patients. No negative clinical reactions were recorded and during hospitalisation average weight increase was 39.8 g/day. The follow-up of the patients showed that ass' milk was tolerated without any problems up to an age ranging from 15 to 20 months, when cow's milk was reintroduced in some patients. PMID- 1593373 TI - Antral and duodenal motor responses to duodenal feeding in preterm and term infants. AB - In the fasting state, antral motor activity is similar in preterm and term infants, but the antral responses to feeding have not been compared in preterm and term infants. The purpose of this study was to use low-compliance, continuous perfusion manometry to compare antral and duodenal feeding responses in 13 preterm and nine term infants within the first 14 days of life. Confirming our previous studies, fasting antral motor activity was similar in preterm and term infants, but duodenal activity differed. Individual duodenal cluster activity was of shorter duration in preterm than in term infants (p less than 0.01). Motor activity in antrum and duodenum changed in both groups of infants in response to an intraduodenal milk infusion of 4 ml/kg/2 h; however, the nature of the change varied in the two regions. In term infants, the number of antral pressure waves, the duration of antral clusters, and the antral motility index decreased by one third or more during feeding when compared with fasting (all p less than 0.05). In contrast to the decrease in antral activity in response to feeding, the duodenal motility index and cluster activity increased significantly during feeding compared with fasting (both p less than 0.05). The divergent response of antral and duodenal motor activity in response to feedings was also seen in preterm infants. Antral pressure waves, the duration of antral clusters, and the antral motility index were decreased during feeding (all p less than 0.005 or less).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593374 TI - Type of acidosis and clinical outcome in infantile gastroenteritis. AB - To explore different types of metabolic acidosis in acute gastroenteritis of infancy, and to correlate it with nutritional status and clinical outcome, we examined prospectively 27 consecutive infants admitted with moderate to severe dehydration and arterial blood pH less than or equal to 7.20. Serum anion gap, creatinine, divalent cations (Ca, Mg), and the anionic contribution of total protein, lactate, and phosphate as well as ketones and urine pH, were determined on admission and compared with age-matched controls. Twenty infants (Group A) presented with normal anion gap (13.1 +/- 2.7) associated with hyperchloremia (115.8 +/- 4.2 mmol/L, p less than 0.01) and diminished bicarbonate (9.7 +/- 2.4 mmol/L, p less than 0.01), compared with controls. The other seven infants (group B) demonstrated an increased anion gap (26.7 +/- 3.2, p less than 0.01), associated with significant elevations of lactate (3.4 +/- 0.7 mmol/L, p less than 0.001), total protein (93.4 +/- 12.3 g/L, p less than 0.01), as well as phosphate (2.3 +/- 0.2 mmol/L, p less than 0.01) and creatinine (164.9 +/- 45.1 mumol/L, p less than 0.001), compared with controls. No significant deviations of blood divalent cations or ketones were noted in both groups. Urine pH was less than or equal to 5.5 in all subjects. Analysis of nutritional status and clinical outcome in both groups revealed significant differences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593375 TI - Levels and molecular forms of immunoreactive trypsin and chymotrypsin in amniotic fluids from normal and cystic fibrosis fetus: evidence for a lack of activation of proteolytic zymogens in cystic fibrosis fetus. AB - We previously suggested that an activation defect of pancreatic proteolytic zymogens in newborns suffering from cystic fibrosis (CF) might contribute (by an adaptative-like process) to the significant increase of the serum trypsin level observed in the disease at birth. To give support to this hypothesis we studied two pancreatic enzymes: trypsin 1 (IRT) and chymotrypsin A (IRChT) by noncompetitive enzyme immunoassays in amniotic fluids taken at 17-18 weeks of pregnancy. In normal fluids (102), the levels of the two enzymes were widely dispersed between 5 and 100 micrograms/L. A similar pattern was observed for the fluids with a 1 in 4 risk of CF with a normal outcome (24). In contrast, the levels of pancreatic enzymes in the fluids with affected fetus (40) were always below 45 micrograms/L for IRT and 55 micrograms/L for IRChT and most of them were under 20 micrograms/L for both enzymes. The molecular forms of IRT and IRChT in amniotic fluids were studied by gel filtration. In amniotic fluids with affected fetus, a major form of IRT was eluted in a position consistent with the elution of proteins around 25 kDa and two peaks of IRChT were eluted at 75 kDa and 25 kDa. These patterns are similar to those observed in normal serum when zymogens are present and are quite different from the patterns obtained by gel filtration of amniotic fluids with normal outcome.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593376 TI - Intestinal permeability to 51Cr-EDTA and orocecal transit time in cystic fibrosis. AB - Intestinal permeability was investigated in 16 children with cystic fibrosis and 14 age-matched controls, making use of 51Cr-EDTA as probe molecule. Orocecal transit time was also evaluated using the lactulose/hydrogen breath test. There was an increase in permeability to 51Cr-EDTA in patients with cystic fibrosis (mean 13.62%) compared with the control group (mean 1.08%). The orocecal transit time was prolonged in patients with cystic fibrosis compared with controls. Mean fasting breath hydrogen concentration was significantly greater in cystic fibrosis patients (13 ppm) compared with control patients (3 ppm). There was no correlation between the percentage of 51Cr-EDTA excreted and the orocecal transit time in either control or cystic fibrosis patients. PMID- 1593377 TI - Persistent diarrhea and malnutrition--the impact of treatment on small bowel structure and permeability. AB - Previous studies using dual sugar permeability tests suggested that damage to the small intestinal mucosa plays an important part in the development of persistent diarrhea in The Gambia. The present study has extended these findings by examining the effect of nutritional rehabilitation on intestinal permeability and mucosal morphology. Intestinal permeability, measured by lactulose:mannitol (L:M) absorption, and mucosal structure, measured by a quantitative, computerised morphologic technique, were evaluated in 20 children before and after such treatment. L:M ratios were high on admission, (0.66 +/- 0.36) and, despite some temporary improvement, did not significantly improve (0.49 +/- 0.30) following rehabilitation for one month. The changes in L:M ratio were largely due to an increase in lactulose absorption, showing that the small intestinal mucosa becomes more "leaky" as a result of nutritional rehabilitation. Although no correlation was found between measures of intestinal permeability and mucosal morphology, nutritional restitution was associated with a significant increase in size of the mucosal crypt cell compartment, but not in villous epithelial volumes during the same period. It is necessary to establish, by further prospective studies, the interval required for full restitution of small intestinal structure and function during treatment for persistent diarrhea. PMID- 1593378 TI - Relationship of common laboratory parameters to the activity of Crohn's disease in children. AB - The Pediatric Crohn's Disease Activity Index (PCDAI) has been proposed as a simple instrument to aid in the classification of patients by disease severity. The PCDAI includes subjective patient reporting of symptoms, physical examination, nutritional parameters, and several common laboratory tests (hematocrit, erythrocyte sedimentation rate, albumin). In this report we examine the relationship of each of the laboratory parameters to the PCDAI, as well as to a modified Harvey-Bradshaw Index score and physician global assessment of disease activity. Data were gathered from the clinical and laboratory observations from 133 children and adolescents at 12 pediatric gastroenterology centers in North America. A statistically significant relationship (p less than 0.05) was noted between each of the laboratory tests and the PCDAI for patients with either disease limited to the small bowel or in those with colonic involvement. For patients with disease limited to the small bowel, a statistically significant (p less than 0.05) relationship was also noted between the three laboratory parameters and the modified Harvey-Bradshaw Index and global assessment. For patients with large-bowel involvement, the erythrocyte sedimentation rate was statistically related to the modified Harvey-Bradshaw Index and global assessment (p less than 0.01), as was hematocrit to global assessment (p less than 0.01). Although the laboratory parameters used in the PCDAI appear to generally reflect disease activity in most patients, no single laboratory test is adequate to reflect disease activity in all patients. Future work will need to identify additional laboratory measures to reflect the inflammatory process and serve as important adjuncts in the assessment of disease activity. PMID- 1593379 TI - Successful late Kasai portoenterostomy. AB - This article describes an infant with extrahepatic biliary atresia who underwent a successful hepatoportoenterostomy at age 132 days in spite of a delay in diagnosis. Contributing to the delay in diagnosis of this case were the lack of appreciation of alcoholic stools, the presence of a gallbladder and distal common bile duct on ultrasound examination, and insufficient biopsy material for interpretation. This case emphasizes the variability in presentation and potential difficulties in diagnosis and the need for intraoperative cholangiogram and exploratory laparotomy in such cases. An approach to the patient with extrahepatic biliary atresia who is diagnosed late is discussed. A successful outcome can be achieved for such patients. PMID- 1593380 TI - Transient protein-losing hypertrophic gastropathy associated with Mycoplasma pneumoniae infection in childhood. AB - A 3-year-old boy with transient protein loss due to hypertrophic gastropathy is described. Serologic evidence of concomitant Mycoplasma pneumoniae infection was present. Although sometimes associated with infections, protein-losing hypertrophic gastropathy has not been reported previously in association with Mycoplasma pneumoniae infection. PMID- 1593381 TI - How super can "super-ORS" get? PMID- 1593382 TI - Nutrition and AIDS. PMID- 1593383 TI - Prevalence of hepatitis C virus in Japanese children with non-A, non-B hepatitis and those with elevated liver enzymes after repeated blood transfusions. PMID- 1593384 TI - Religion and drug use. AB - This study is a secondary analysis of data gathered under the sponsorship of the Utah State Division of Alcoholism and Drugs in 1989. The researchers concluded that there is a difference in frequency of alcohol use, source of alcohol, and age of first alcohol use among LDS, Other Religions and No Religion subgroups. There is no significant difference found among the various religious subgroups for age of first marijuana use of quantity of alcohol use. For all religions except Jews, a lower percentage of Utahns used alcohol than their national counterparts. A theoretical model for LDS Drug use is presented. PMID- 1593385 TI - Drugs in the womb: college student perceptions of maternal v. fetal rights. AB - A survey of 523 college undergraduates regarding a pregnant woman's culpability for the use of specific drugs during pregnancy indicated that a rank order of the relative safety of the drugs existed in the minds of the respondents. Tobacco, alcohol and aspirin were perceived as similar in their consequences to the fetus, while cocaine was considered to be the most deleterious and Accutane, the least deleterious. Although 75 percent would imprison a pregnant woman who used cocaine, only 16 percent would do so for the use of Accutane, a prescription drug. The 87 percent of the students who believed that the fetus was a child, were more likely to consider the use of the five drugs during pregnancy as a form of child abuse and were also more willing to imprison the "offending" women. It was suggested that drug education programs need to place more emphasis on the potentially deleterious consequences of prescribed medicines to the fetus. PMID- 1593386 TI - State-level evaluations of school programs funded under the Drug-Free Schools and Communities Act. AB - Although the Drug-Free Schools and Communities Act of 1986 and the 1989 Amendments to the Act require states to evaluate their drug-education programs, no guidelines for conducting these evaluations have been produced, and little has been reported on how the states are conducting such evaluations. In this article, the results of a telephone survey on current state-level efforts to evaluate school programs funded under the Act are reported. Some states report studies of the implementation of the program and some report drug- and alcohol-use surveys. Together, these two types of evaluation efforts form the foundation of an approach for conducting evaluations under the Act. Reasons are presented why experimental and quasi-experimental designs might be inappropriate and impractical for the evaluations, and an evaluation approach linking program implementation findings and drug- and alcohol-use survey results is suggested. PMID- 1593387 TI - An evaluation of prototype school-based peer counseling program. AB - This study reports short-term outcome evaluation results of a school-based peer counseling (PRC) program as implemented by North Forsyth High School during January 1990-February 1991. The PRC program is evaluated in terms of: 1) the content of the program as evaluated by the PRC trainees; 2) the quality of the PRC instructor as perceived by these trainees; 3) several instrumental objectives deduced from the PRC training program; and 4) the degree to which the program was able to reach other students at North Forsyth during the time the PRC was in operation. In the absence of a control group, the treatment effect of the program is determined in terms of individual growth curve models. Through the multiple evaluation designs employed in this research, it has been learned that a significantly larger proportion of students in the PRC group had more favorable attitude toward the content of the PRC program when compared to the content of what they learned from their regular school curricula. Furthermore, a significantly larger proportion of students in the PRC program reported more favorable attitude toward their instructor than their regular school teachers. The PRC program was able to elicit an improvement of trainee self-esteem (p less than .01) and their social values (p less than .05) between pre and post of the Peer Training Evaluation Instrument. In terms of client access, 18.4 percent of the totality of potential clients at North Forsyth have been reached through sixty-one peer counselors sanctioned by the school. PMID- 1593388 TI - Role rehearsal and efficacy: two 15-month evaluations of a ninth-grade alcohol education program. AB - A ninth-grade alcohol education program aimed at reducing drinking, drinking and driving, and riding with a drinking driver was developed on the basis of problem behavior theory, social cognitive theory and role theory. In Year 1 the program was taught by Social Studies teachers to half of the eighty-four ninth-grade classes in all nine junior high schools in a single school system; the other half served as controls. In Year 2 the program was taught to the ninth-grade students of the same school system by English teachers. Students' knowledge, skills and practices were measured before and four-six weeks and one year after the program. Results indicated significant increases in knowledge and perceived ability to resist pressures to drink among experimental students. No significant differences were noted for the drinking or the drinking and driving practices of either group. One year after the program, significantly fewer students in the experimental classes reported riding with a driver who had been drinking. Results suggested that English teachers were more effective than Social Studies teachers in teaching this program. PMID- 1593389 TI - Characteristics of smokeless tobacco use among high school football players as related to type of smokeless tobacco and period of use. AB - The present study was conducted to assess differences in the behavioral and demographic characteristics of snuff (dip) users as compared to users of chewing tobacco. High School football players (1116) were surveyed concerning their use and perceptions of smokeless tobacco. Adolescent athletes who tried smokeless tobacco were more likely to be white, to use cigarettes, alcohol, and cigars and to have family users than those who never tried. Initial use was highest before the age of fourteen years and was influenced by friends, curiosity and family. Dippers tended to initiate use because of friends, while chewers started because of family users. Users of both dip and chew started primarily because of curiosity. Users of both were more likely to consume greater amounts to alcohol and cigarettes and to smoke cigars and pipes. It appears that the longer smokeless tobacco is consumed, the more likely both dip and chew will be used. Users of smokeless tobacco for more than two years tended to consume more of the product each week, used it for more hours/day, initiated use at an earlier age, and used it more often at school and work than those using it for less than two years. Use of cigars/pipes, consumption of alcohol, and quantity of cigarette consumption increased significantly with longer duration of smokeless tobacco use. Intervention and prevention programs would be helped by understanding differences between users of various smokeless tobacco products and differences related to the duration of use. In addition, further analyses of smokeless tobacco users should study chewers, dippers, and users of both separately. PMID- 1593390 TI - Evaluation of an educational intervention upon knowledge, attitudes, and behavior concerning drinking/drugged driving. AB - The Contra Costa County educational program for juveniles found guilty of driving under the influence (DUI) was evaluated. Over 600 juveniles convicted of DUI from 1983 to 1988 formed the study group for this research and of these over 100 participated in the educational program. Assessment of program participants was conducted for knowledge, attitudes and behavior. Participants demonstrated increased knowledge, stronger attitudes against driving under the influence, and less risky alcohol and automobile related behaviors. County juvenile records analyzed by the logit procedure showed that class participants had a significantly lower number of repeat offenses compared to non-program participants that could not be explained by race, offense severity, age or gender. PMID- 1593391 TI - Pedagogical patronizing of the pharmacodynamic promises of illicit drugs. AB - A review of popular drug education textbooks and curricula indicated most juxtapose the physiologic effects of licitly manufactured drugs under headings representing illicitly prepared drugs. This misrepresentation ignores the literature, which is undivided, in reporting that illicit drugs contain adulterants and substitutes such as: sodium acetate, sodium cyclamate, dolomite, acetaminophen, gypsum, mannitol, inositol, lidocaine, amydricaine, benzocaine, caffeine, ephedrine, intercaine, phenylpropanolamine, piperocaine, procainamide, azopyridine, bromodiphenhydramine, ibuprofen, methaqualone, phenobarital trazodone, acetylcodine, codeine, quinine, quinidine, thallium, arsenic and strychnine. The temptation to extrapolate the results of licitly pure drug lots administered at precisely measured doses to represent the pharmacodynamics of illegally prepared drug lots administered at indiscernible doses must be avoided in drug educational resources. There is a pressing need to correct the factual base, both implied and suggestive, of drug education resources regarding the purity and toxicity of illicitly manufactured and purchased drugs. PMID- 1593392 TI - Psychological adjustment of children with asthma: effects of illness severity and recent stressful life events. AB - Although children with chronic illness are at greater risk for decreased psychological adjustment than physically healthy children, little is known about the factors that lead to increased risk. Eighty-one children with asthma between the ages of 6 and 14 years and their parents participated in a study to determine the relative contribution of background variables (age, gender, and socioeconomic status), recent stressful life events, and illness severity to psychological adaptation. Overall 11.5% of the children had CBCL Total Behavior Problems scores above the 98th percentile. Multiple regression revealed that lower SES, negative life change, and high illness severity were predictive of less optimal psychological adjustment. The results highlight the need for interventions to improve coping with both disease and nondisease issues. PMID- 1593393 TI - Otitis media, language development, and parental verbal stimulation. AB - Examined the impact of recurrent otitis media in the first 3 years of life on verbal abilities of 3- to 4-year-old children and the potential for parental verbal stimulation to buffer the negative effects of intermittent hearing loss. Fathers and mothers of 56 children with variable histories of otitis media participated in videotaped parent-child interactions that were used to code level of parental verbal stimulation. Measures of the children's verbal abilities were the McCarthy Verbal Scale Index and a score for the child's verbalizations with each parent. Active and engaging parental verbalizations appeared to buffer the child's developing verbal abilities from the deleterious effects of recurrent otitis. Post hoc analyses examined the implications of task structure and parent sex on parent verbal stimulation. Discussion addresses the importance of paternal involvement for the home language environment and implications for intervention. PMID- 1593394 TI - Neurodevelopment in infants and preschool children with congenital hypothyroidism: etiological and treatment factors affecting outcome. AB - Studied global intelligence and specific abilities of children from 1 to 5 years old, 108 with congenital hypothyroidism (CH) diagnosed by newborn screening and 71 sibling controls. Intelligence levels of the CH group were within the normal range but differed significantly from controls at age 5. CH demonstrated a language deficit at age 3, which diminished with age, as well as significantly poorer visuospatial and verbal skills at age 5. Children with absent thyroid glands or evidence of hypothyroidism in utero were outperformed by other CH children in most ability areas from 1 year on. Different components of ability were correlated with specific factors reflecting timing or duration of thyroid hormone deficiency, suggesting unique critical periods of thyroid hormone sensitivity for different specific cognitive abilities and their neural substrates. It is concluded that even though screened CH children are markedly improved by neonatal diagnosis, they are still at risk for subtle irreversible deficits, which depend on factors such as type, age at onset, and duration of disease. PMID- 1593395 TI - Health assessments of youngsters with insulin-dependent diabetes. AB - In this study with youngsters with insulin-dependent diabetes, there were a number of significant correlations among psychological variables. However, with two exceptions, metabolic indices were not correlated with psychological variables or symptom reporting. Correlations involving aspects of symptom reporting suggest relationships with psychological factors. Implications for treatment decisions are presented. Additionally, theoretical, psychometric, and methodological considerations are discussed. PMID- 1593396 TI - Development of an instrument to measure the behaviors and expectations of parents of young children. AB - Designed a study to develop an instrument, the Parenting Inventory: Young Children (PI), to assess the behaviors and developmental expectations of parents who have a child between 1 and 4 years of age. Item development for the PI occurred within a developmental-environmental theoretical framework and was based on literature reviews and clinical experience. Experts working with parents and/or children and parents of young children established the content validity of the items. The PI was tested with a sample of 1,140 mothers. This sample was representative of the population from which it was drawn, a large urban area, in terms of the sample children's sex and ethnicity. A diverse range of socioeconomic levels were included. The resulting 100-item PI was found to reliably measure three aspects of parenting: Expectations, Discipline, and Nurturing. These factors demonstrated good internal consistency and test-retest reliability. Future research needs relative to the continued development of the PI are addressed. PMID- 1593397 TI - A study of the stability of W/O/W multiple emulsions. AB - The stability of W/O/W emulsions has been studied in batch agitators. The surfactants suitable for W/O/W emulsions were screened and the factors affecting the emulsion stability were also studied. Results showed that polyamine E644 was an excellent emulsifier for W/O emulsions since the emulsion stabilized by it has not only good stability but also shows smaller swelling. The stability of the emulsion increases with increase in membrane viscosity and concentration of surfactant, but decreases with increase in concentration of the internal reagent in the internal phase and the carriers in the membrane. Raising the agitation speed and the time for preparing the W/O emulsion is beneficial to membrane stability due to formation of smaller internal droplets, but raising the speed for dispersing the W/O emulsion in the external phase results in an increase in membrane breakage. PMID- 1593398 TI - Use of polylactic acid for the preparation of microparticulate drug delivery systems. AB - This report reviews the development of particulate drug delivery systems technology based on polylactic acid (PLA). The following methods used to produce PLA microparticles are considered: emulsion solvent evaporation, emulsion solvent extraction, interfacial phase deposition, spray coating, and the melting method. The different preparation processes and parameters used, the characteristics of microparticles obtained and those parameters affecting the characteristics of these systems, are discussed. PMID- 1593399 TI - Sustained-release dosage form of oxolamine citrate: preparation and release kinetics. AB - One of the principal uses of microencapsulation for pharmaceuticals has been the preparation of sustained-release dosage forms which have been usually presented in the form of a suspension or gel. However, a non-disintegrating tablet would be a better formulation to obtain sustained-release effect. Microencapsulation has been employed to provide protection of the core material against atmospheric effects, to cover the unpleasant taste and to enhance the stability. A number of drugs have also been encapsulated to reduce gastric and other GI tract irritations, to alter release properties and to change availability. Oxolamine citrate is one of the synthetic derivatives of 3,5-disubstituted 1,2,4 oxodiazole, used particularly for its antitussive activity. The usual dose of the drug is 200 mg given four times a day. Its use was limited by side-effects of nausea and vomiting. In order to prevent the disadvantages caused by taking the drug four times daily, and to reduce the side-effects, a sustained-release dosage form of oxolamine citrate was prepared by the microencapsulation technique and microcapsules thus formed were pressed into tablets. Dissolution tests were done with microcapsules and tablets formed by microcapsules by using the USPXXI paddle method and dissolution kinetics were studied and evaluated. PMID- 1593400 TI - Association of cyclosporin to isohexylcyanoacrylate nanospheres and subsequent release in human plasma in vitro. AB - Polyisohexylcyanoacrylate nanocapsules containing cyclosporin were prepared by mixing in a 1:2 ratio an oil/ethanol solution of monomer and drug with an aqueous phase. Drug nanoencapsulation rate was controlled by its partition coefficient between the inner (organic) and outer (aqueous) phases. Thus highest encapsulation yields (88 per cent) were achieved by reducing cyclosporin solubility in the aqueous phase, i.e. by reducing ethanol concentration under reduced pressure, achieving a 3-fold volume reduction. Due to the relative insolubility of cyclosporin in water, no drug was released from the nanocapsules during storage in this injectable vehicle. Upon a 1/5 dilution in human plasma at 37 degrees C in vitro around 40 per cent of the initially encapsulated cyclosporin diffused quickly out of the capsules and an equilibrium was reached, the drug being most likely dissolved in the fatty compartment of the plasma such as lipoproteins, etc. This release mechanism is different from plain polymeric nanoparticles. Indeed, in this case the drug was released in two phases: an initial burst (around 60 per cent) of adsorbed drug as a result of the dilution, followed by a slow release (around 20 per cent over 3 h) which is likely to result from the progressive enzymatic erosion of the polymer. The initial burst was markedly more pronounced (around 80 per cent) when nanoparticle suspensions were evaporated to 1/3 of their initial volume under reduced pressure. Finally, experiments performed at 0 degree C allowed a reduction of the fraction released immediately from both types of nanospheres, probably because of a reduced solubility in plasma. In the case of nanoparticles the second phase of slow release is also inhibited at 0 degree C, in agreement with an enzymatically controlled release mechanism. PMID- 1593401 TI - Microencapsulation of menadione sodium bisulphite with polydimethylsiloxane by the spray-drying process: characterization by thermal analysis. AB - Menadione sodium bisulphite was microencapsulated with a polydimethylsiloxane membrane using spray-drying technology. Tests were performed using laboratory equipment and a Niro Atomizer pilot plant to scale up the process. The products were characterized with differential thermal analysis (DTA) and chemical and physical methods. Many differences between raw material and microencapsulated powder result from DTA data. The thermal characterization confirms that the spray drying microcoating could be used to protect powder from the oxidative actions of the atmosphere. PMID- 1593402 TI - Naming microcapsules. AB - A system of nomenclature is proposed whereby microcapsules are named after their 'core', 'wall' or 'both core and wall', as may be desired. The proposed nomenclature provides short descriptive names, and eliminates the need for lengthy phrases often used in the microencapsulation literature. PMID- 1593403 TI - Encapsulation of doxorubicin in neutral liposomes by passive methods: evidence of drug-lipid interaction at neutral pH. AB - Doxorubicin, an antineoplastic agent, was encapsulated in liposomes of dipalmitoylphosphatidylcholine with or without cholesterol, by the extrusion procedure. Doxorubicin was added to the lipid before drying, or was present in the rehydration buffer, and the influence of the method of encapsulation on size and polydispersity was determined by photon correlation spectroscopy. Results showed an important interaction between doxorubicin and liposomes, although cholesterol-containing vesicles were those that underwent the strongest insertion of the drug. One important parameter, which determined the extension of such interaction, was the curvature of the vesicle bilayer. So, liposomes extruded through a 50 nm membrane filter suffered the highest relative size variation in comparison with empty liposomes. Doxorubicin also produced an increase in polydispersity of vesicle population; therefore its presence resulted in some fusion and/or aggregation processes. The stability of liposomes was dependent on lipid content, on the method of drug trapping and on the presence or absence of such drug. Encapsulation efficiency seemed to be inversely related to liposome stability. Maximal values, which never exceed 0.015 +/- 0.005 mumol of drug per mumol of lipid, were obtained when the drug was dried together with the lipids. PMID- 1593405 TI - Effect of viscosity and interfacial tension on particle size of cellulose acetate trimellitate microspheres. AB - The influence of the viscosity of the internal and external phases and the interfacial tension between the two phases, in the emulsion type of microencapsulation system was investigated. The viscosity of mineral oil (external phase) was measured by a capillary viscometer and the viscosity of cellulose acetate trimellitate solution (internal phase) was measured by a Brookfield viscometer. The viscosity of the two phases were measured prior to mixing and at 5 and 60 min after mixing the phases. It was observed that the viscosity of the mineral oil phase prior to mixing had little effect on the average diameter of the microspheres, until a high concentration of light mineral oil was used. A graph of viscosity ratio of the internal phase to the external phase shows that a minimum viscosity ratio may be required before particle size increases. Results are discussed with respect to viscosity effects of mineral oil and polymer solution, as influenced by the solvent uptake by the mineral oil. The interfacial tension between the two phases was measured by pendant drop method. Interfacial tension was measured at 5 and 60 min after the two phases came in contact. The interfacial tension between the mineral oil and polymer solution ranged up to 7 dyne/cm and the particle size was not affected appreciably by the interfacial tension. Particle size and morphological analysis of the microspheres were determined using microscopy and scanning electron microscope. PMID- 1593404 TI - Preparation of multi-phase microspheres of poly(D,L-lactic acid) and poly(D,L lactic-co-glycolic acid) containing a W/O emulsion by a multiple emulsion solvent evaporation technique. AB - Multi-phase microspheres of poly(D,L-lactic acid) (PLA) or poly(D,L-lactic-co glycolic acid) (PLGA) containing a water-in-oil (W/O) emulsion were prepared by a multiple emulsion solvent evaporation technique. Acetonitrile was used as the solvent for the polymers and light mineral oil as the dispersion medium for the encapsulation procedure. Process and formulation parameters to optimize the microencapsulation of a W/O emulsion containing water-soluble drugs were investigated. Drug loading efficiencies of 80-100 per cent were obtained under specific preparative conditions. The drug loading efficiency in the microspheres was dependent upon the ratio of the W/O emulsion to polymer and the concentration of surfactant in the mineral oil. Compared to conventional microspheres, in which fine drug particles are homogeneously dispersed in the polymer beads, the multi phase microspheres permit the higher encapsulation efficiency of water-soluble drugs and eliminate partitioning into the polymer-acetonitrile phase which results in low encapsulation efficiency with conventional solvent evaporation techniques. PMID- 1593406 TI - Aminophylline targeting to lung: optimization of the size and drug loading of albumin microspheres. AB - Aminophylline, a bronchodilator, was considered a suitable drug for targeting to the lung to treat emphysema. Factorial concept was utilized to optimize the size and drug loading of microspheres suitable for targeting. Aminophylline-loaded albumin microspheres were prepared by heat denaturation adjusting the manufacturing variables, namely albumin concentration, drug concentration, water oil phase ratio and stirring rate at low and high levels. For two levels of the four variables the experimentation was performed in 16 batches. A good yield of well-defined microspheres of the size range, 2-30 microns, were obtained from all the batches. The drug loading was found maximum (36.33 per cent) in batch XV of microspheres prepared with low albumin concentration, high drug concentration, low water-oil phase ratio and low stirring rate. The least number (13 per cent) of microspheres of batch XV were below 7 microns and the remaining 87 per cent were above this size. Considering the payload and size, microspheres of batch XV were found suitable for targeting to the lung. PMID- 1593407 TI - Inhibition of liposomal lipid peroxidation by spermidine. AB - Spermidine was found to inhibit the in vitro formation of thiobarbituric acid reactive material from sonicated vesicles of rat brain and individual phospholipids, especially in the presence of externally added iron. With arachidonic acid incorporated liposomes spermidine inhibited lipid peroxidation in the presence or the absence of Fe2+, to similar extent. Thus spermidine inhibition of lipid peroxidation may not be entirely iron-dependent. PMID- 1593409 TI - Significance of early healing events on periodontal repair: a review. AB - Wound healing in an incisional wound is a highly predictable process which has been studied extensively hour-by-hour and day-by-day. Healing in a periodontal defect following gingival flap surgery is, conceptually, a more complex process as one wound margin consists of calcified tissue, including the avascular and rigid root surface. Another complicating factor in this wound healing is the transgingival position of the tooth. Experimental studies, however, have indicated that healing at a dento-gingival interface under optimal conditions occurs at the same rate as in a skin wound. Generally, periodontal healing is characterized by maturation of gingival connective tissue, limited regeneration of alveolar bone and cementum, and the formation of a long junctional epithelium. Such observations have nurtured the hypothesis that the epithelium of the surgical flap needs to be prevented from early access to the root surface during the healing period to achieve connective tissue repair of the root surface gingival flap interface. Recent experimental findings suggest, however, that connective tissue repair to the root surface following reconstructive periodontal surgery is a function of the establishment and maintenance of a root surface adhering fibrin clot. Since fibrin adherence to the wound margins is a natural event, it is additionally suggested that apical migration of the gingival epithelium in periodontal surgical wounds may only follow interruption of the adherence of the fibrin clot to the root surface. PMID- 1593408 TI - The effect of hygiene instruments on dentin surfaces: scanning electron microscopic observations. AB - The present study consists of two separate parts. The first section is an in vitro evaluation of the relative abrasiveness of some hygiene instrumentations commonly used during maintenance therapy. In the second section, one of the instruments, a recently developed plastic tip for use on a sonic scaler, was examined for its ability to remove dental plaque from root surface specimens instead for 5 weeks in the oral cavities of dogs. The in vitro study was performed on recently obtained dentin specimens where a ridge had been machined parallel to the long axis of the tooth. The sonic scaler fitted with the plastic tip gave considerably less removal of dentin and a smoother dentin surface than the curet, the rubber cup with polishing paste, or the sonic scaler with an ordinary metal tip. These findings further demonstrated that the plastic tip was able to efficiently remove 5-week old dental plaque from experimental root surface areas within a time frame of 5 seconds. The new plastic tip may be valuable in maintenance therapy giving less risks for iatrogenic effects on the root surfaces than other debridement methods. PMID- 1593410 TI - Effects of sodium meclofenamate on postoperative pain following periodontal surgery. AB - The analgesic activity of single doses of meclofenamate (100 mg) was compared to aspirin (500 mg) and to placebo on 99 outpatients with moderate to severe pain following periodontal surgery under double-blind conditions. Pain intensity differences scores (PID) at the first, second, and third hour after the ingestion of the first capsule of each medication were used to determine the analgesic efficacy of the studied drugs. Kruskal Wallis test followed by the Mann-Whitney rank sum test were used in the statistical analysis of results. Meclofenamate was statistically superior to placebo and superior to aspirin in the second hour of evaluation, while aspirin was not superior to placebo during the 3-hour period of pain evaluation. It is concluded that meclofenamate is a non-steroidal antiinflammatory drug with interesting analgesic properties which can be used as directed as an alternative to aspirin or acetaminophen for the control of postoperative pain following periodontal surgery. PMID- 1593411 TI - Re-interpretation of the evidence for X-linked dominant inheritance of juvenile periodontitis. AB - Several studies have provided evidence supporting the inheritance of juvenile periodontitis (JP) in a Mendelian fashion, and both X-linked and autosomal modes of transmission have been proposed. Re-examination of the evidence for the X linked dominant hypothesis reveals that two assumptions were crucial in favoring the X-linked rather than an autosomal hypothesis of JP transmission. The first assumption was that females are more likely than males to have JP by ratios of approximately 2.5:1. The second key observation was the reported lack of father to son transmission of the trait. However, the data that these assumptions were based on may be interpreted differently. Although the number of females reported to be affected by JP is greater than the number of affected males, this is probably a reflection of the greater number of females incorporated into these studies. When the proportions of affected males and females are examined, rather than total numbers of affected individuals, the proportion of affected males and females is similar. Additionally, the reported lack of father to son transmission for JP appears to be the result of incomplete family data. The female ascertainment bias inherent in many JP studies, compounded by the lack of male participation in such studies, appears to have resulted in the perception of a lack of male to male transmission of JP. This lack of observed father to son transmission of JP in incomplete data sets has been regarded as proof of no male to male transmission for the trait. Studies of more complete family data, however, do document father to son transmission of JP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593412 TI - Clinical effectiveness of subgingival irrigation with a pulsated jet irrigator versus syringe. AB - Previous studies have shown clinical and microbiological improvement with subgingival irrigation particularly after scaling and root planing. In this study we monitored the effects of saline irrigation on non-treated periodontal pockets. Ten subjects with severe periodontal disease and symmetrical lesions on multirooted teeth were selected. They had not received periodontal treatment or antibiotics for the previous 6 months. Patients were given simplified oral hygiene instructions. Neither scaling nor root planing was provided during the study. Two teeth were randomly selected per quadrant for subgingival irrigation with saline solution. One side was treated with a syringe and the other side with a pulsated jet irrigator with a modified tip, professionally administered. Clinical parameters (pocket depth, plaque index, gingival index, crevicular fluid, bleeding index, attachment level, and subgingival microflora) were evaluated on days 0, 15, 30, 60, and 90. Both subgingival irrigation products induced changes (reductions) in these indices during the study. Significant differences (P less than 0.001) with the oral irrigator were found for the following parameters: microscopy, pocket depth, crevicular fluid, and plaque index. In this study, professionally administered saline irrigation with a pulsated jet irrigator was more effective than syringe treatment with the same solution. Neither treatment resulted in a detectable gain in probing attachment level. Since gain in attachment level is achievable by other techniques, neither of these subgingival irrigation procedures alone can be considered adequate for periodontal therapy. PMID- 1593414 TI - Topographical characteristics of root trunk length related to guided tissue regeneration. AB - Thirty-seven molars with 94 furcations were selected for a topographical study of root trunks to clarify the possible factors which may affect the clinical application of guided tissue regeneration technique. A pre-determined plane was marked on the root trunk of each tooth 1 or 2 mm below the cemento-enamel junction (CEJ). The plane followed the presumed position of the occlusal border of the Teflon membrane. Cross sectioning of the root was then performed following the plane, and the width of the gap between the membrane and root surface was measured with the aid of a stereomicroscope. The results revealed, within the limited samples of this study, 94% of the furcations possessed variant depth of developmental concavities on the root trunks. These superficial irregularities at the entrances of furcations may prevent complete adaptation of the coronal microstructure of the Teflon membrane along their root surfaces. The width of the gaps between root surfaces and membranes ranged from 0.000 mm to 2.250 mm for all tooth samples. The study implied that the subgingival application of guided tissue membranes 1 to 2 mm below CEJ cannot ensure complete adaptation of furcation defects with their coronal microstructures in the majority of molars. PMID- 1593413 TI - Clinical criteria for the definition of "established periodontitis". AB - The objective of The Present study was to define criteria for the diagnosis of "established periodontitis." This term will define subjects who have demonstrated clinical attachment loss, and as such can be considered to have periodontitis. Using these criteria, healthy and established periodontitis subjects were compared with respect to gender, race, and age. Five hundred and eight subjects including 248 females and 260 males between the ages of 25 to 73 (mean 44.6 years), were examined in this study. The clinical examination included: plaque assessment index (PAI); gingival assessment index (GAI); probing pocket depth (PPD); and clinical attachment level (CAL). The mean and frequency distribution of these parameters were analyzed by age and gender. CAL (mean 2.12 mm) showed constant and significant increases with age, ranging from a mean of 1.63 mm in subjects 25 to 34 years of age to a mean of 2.65 mm in subjects 65 to 74 years of age. Males exhibited higher mean values than females for all the measured parameters, which were statistically significant for PAI, PPD, and CAL. The frequency distribution of subjects with PPD and CAL beyond certain threshold levels showed an exponential decline and was correlated to both the severity of the most involved site as well as the number of sites beyond threshold levels. The clinical entity of "established periodontitis" is suggested based on the presence of CAL greater than or equal to 6 mm in 2 or more teeth and one or more sites with PPD greater than or equal to 5 mm. In the present study, 30.5% of the subjects fell into this category.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593415 TI - Cemental tear related to rapid periodontal breakdown: a case report. AB - Cemental tears have been described both in exposed and unexposed cementum. The phenomenon is believed to be elicited by overloading or acute trauma from occlusion. In this case report a patient, with a history of periodontal health, presented with an acute periodontal lesion on the distal aspect of a bridge abutment tooth. Periapical radiographs demonstrated an extensive vertical intrabony defect adjacent to the vital abutment tooth containing a radiopaque "foreign body." Histological examination of the surgically removed "foreign body" revealed a piece of dental cementum with some attached soft tissue. The lesion responded well to a surgical approach. Healing was uneventful and periodontal health was restored. This case illustrates that cemental tear should be considered as a differential diagnostic entity in isolated sites with rapid periodontal breakdown. PMID- 1593416 TI - Soft tissue reactions to non-submerged unloaded titanium implants in beagle dogs. AB - The soft tissue reactions to non-submerged unloaded titanium implants were examined. A total of 24 implants were placed in 6 beagle dogs. The implants differed in their crestal area by having either a rough sandblasted, a fine sandblasted, or a polished surface. After 3 months, all implants were firmly anchored in the bone and had no clinical signs of peri-implant inflammation. Undecalcified histologic sections demonstrated that all implants achieved osseointegration with direct bone contact. The epithelial structures showed a peri-implant sulcus with a non-keratinized sulcular epithelium and a junctional epithelium. None of the sections exhibited epithelial downgrowth to the alveolar crest. In the supracrestal area, a direct connective tissue contact to the implant post was observed. An approximately 50 to 100 microns wide zone of dense circular fibers was found close to the implant surface. It was free of blood vessels and resembled closely an inflammation-free scar tissue formation. This zone was surrounded by a looser connective tissue with a 3-dimensional network of collagen fibers running in different directions. No significant differences concerning soft tissue reactions were found between the 3 implant surfaces. In particular, the length of direct connective tissue contact was similar. Concerning bone reactions, a significantly shorter distance from the top of the implant to the most coronal bone-implant contact was observed for rough surfaces. It is concluded that non-submerged unloaded titanium implants achieved a complication-free tissue integration with a dense connective tissue in direct contact to the implant surface in the supracrestal area, and epithelial structures similar to those around natural teeth. The different surface textures did not influence the healing pattern of the soft tissues, but had an influence on the location of the most coronal bone-implant contact. PMID- 1593417 TI - Spontaneous trait inferences as self-generated primes: implications for conscious social judgment. AB - The priming literature has documented the influence of trait terms held outside of conscious awareness on later judgment relevant to the primed trait dimension. The present research demonstrated that spontaneous trait inferences can serve as self-generated primes. In Experiment 1, Ss instructed to memorize trait-implying sentences (thus spontaneously inferring traits outside of consciousness) showed assimilation effects in judgment. Ss instructed to form inferences from these sentences (thus consciously inferring traits) showed contrast effects. Experiment 2 demonstrated that these findings were due to semantic activation rather than to a general evaluative response. When evaluatively inconsistent trait constructs were primed, similar patterns of assimilation and contrast were found. Implications for the ubiquitous occurrence of priming through the process of social categorization are discussed. PMID- 1593418 TI - Empathic accuracy in the interactions of male friends versus male strangers. AB - In unstructured interactions, male friends were found to be more accurate than male strangers in inferring each other's thoughts and feelings. Plausible reasons for this difference were that friends (a) interacted more and exchanged more information, (b) had more similar personalities and therefore more rapport with each other, and (c) had more detailed knowledge of each other's lives. Data confirmed that the friends did indeed interact more and were more similar in their sociability than the strangers; however, these differences did not account for the friends' greater empathic accuracy. Instead, this was primarily attributable to a difference in knowledge structures, namely, the friends' ability to accurately read their partners' thoughts and feelings about imagined events in another place or time. PMID- 1593419 TI - Effects of distress on eating: the importance of ego-involvement. AB - Schotte (1992) argued that ego threat is not a necessary precondition for the disinhibition of eating in dieters. This article agrees that there are indeed other triggers for disinhibition, as has long been widely acknowledged, but also argues that when distress does act as a trigger for disinhibition, it does so by threatening the dieter's self-image. PMID- 1593420 TI - Vulnerable self-esteem and depressive symptoms: prospective findings comparing three alternative conceptualizations. AB - Across diverse theoretical orientations, vulnerable self-esteem (SE) is thought to act as a diathesis for depression after life stress. In the present study, the roles of trait-level SE, low SE primed by depressed mood, and labile SE in prospectively predicting changes in depressive symptoms in a nonclinical sample (n = 192) were examined. Results indicated that labile SE predicted increases in symptoms. Furthermore, a 3-way interaction (Labile SE x Academic Stress x Initial Depression) suggested that in Ss who were initially asymptomatic, lability made Ss differentially vulnerable to increases in depressive symptoms after stress. In contrast to labile SE, trait-level SE and priming of low SE were relatively weak predictors of changes in depressive symptoms and did not interact with stress. PMID- 1593421 TI - Coping ability, stress, productive load, and symptoms. AB - A study of 450 college students demonstrated (a) the importance of a distinction between self-produced and externally produced stressors, (b) the usefulness of a construct of productive load, and (c) stronger relations of the Constructive Thinking Inventory than of the Hardiness Questionnaire with productive load and with mental and physical symptoms. Because a major path through which coping ability influences symptoms is negative emotions, the widely recommended practice of partialing self-reported negative affect out of relations among coping, stress, and symptoms is often inappropriate. However, as total daily stressors (e.g., hassles) consist largely of self-produced stressors, it is highly confounded with coping ability, and it is therefore important to partial coping ability out of relations between total stressors and other variables. PMID- 1593422 TI - Coping ability, negative self-evaluation, and overgeneralization: experiment and theory. AB - Responses of 3 groups of Ss differing in general coping ability, as measured by the Constructive Thinking Inventory, were compared on matched sets of items that differed according to whether the outcomes were positive or negative and directed at the self or at others. All groups reported widespread overgeneralization to items with favorable outcomes. Groups differed strongly and consistently only in response to unfavorable outcomes directed at the self, with poor constructive thinkers reporting more negative overgeneralization than others following such outcomes. It was concluded that poor constructive thinkers have a selective bias toward making negative inferences about the self, which has widespread implications for their general coping ability. A theoretical framework is presented for understanding why individuals acquire and maintain negative self schemata, which has implications for depression and self-esteem as well as for general coping ability. PMID- 1593423 TI - Biased recollections in older adults: the role of implicit theories of aging. AB - This research explored how older adults recall the traits they possessed at an earlier age. It was hypothesized that older adults' recollections would be related to their theories about aging. In Study 1, a group of older Ss provided their theories concerning how various traits change with age. Another group of older Ss rated their current status on these traits and recalled the status they possessed at a younger age. In addition, a group of younger adults rated their current status on the same traits. On traits theorized to increase with age, older Ss recalled themselves as possessing lower levels at an earlier age than the younger group reported possessing. On traits theorized to decrease with age, older Ss recalled themselves as possessing higher levels at an earlier age than the younger group reported possessing. Study 2 indicated that this effect is obtained regardless of trait positivity. PMID- 1593424 TI - Repression and self-presentation: when audiences interfere with self-deceptive strategies. AB - To defend against threatening feedback, one may avoid and ignore it, or one may dwell on it and think of refutations. Repressors who received threatening feedback privately spent the least amount of time reading it, whereas repressors who received the same feedback publicly spent a long time reading it. Thus, the audience prevented repressors from ignoring threatening feedback; instead, they thought and worried about the partner's (bad) impression of them. Nonrepressors were unaffected by the favorability of the evaluation or the public nature of the situation. Repressors showed superior recall for the few bits of threatening information embedded in a generally favorable evaluation, suggesting that they are especially sensitive when their defenses are down. PMID- 1593425 TI - Relationship between affect and memory: motivation-based selective generation. AB - Two experiments examined the influence of anger and retaliatory motivation on memory for negative material. In the 1st study, 60 male undergraduates memorized words with positive, negative, and neutral semantic connotations. It was found that angered men who expected to retaliate against their provocateur recalled more negative words than other words, and more than Ss in all other affect and evaluation conditions. Angered men in the nonretaliation condition displayed no differences in negative word recall. The 2nd experiment investigated memory for details of a provoking experience. Angered men who expected to retaliate more accurately recalled the details of their provocation, but whether they were given the retaliation information before or after provocation had no bearing on memory for these details. Results are discussed in terms of a motivation-based selective generation hypothesis for the relationship between anger and memory. PMID- 1593426 TI - Intraocular lens biocompatibility. PMID- 1593427 TI - The Binkhorst Medal Lecture. Biologic relationship between poly(methyl methacrylate) intraocular lenses and uveal tissue. AB - Implantation of a poly(methyl methacrylate) (PMMA) intraocular lens (IOL) after cataract surgery is associated with breakdown of the blood-ocular barrier and a foreign body inflammatory response. Although the material is biocompatible, it is not inert. The history of PMMA IOL implantation has reflected mechanical, chemical, and immunological interactions between the IOL and ocular tissues. The common link in these events is instability of the blood-ocular barrier. In this lecture, I discuss the nature of these interactions and present evidence that currently investigated methods of surface modification and capsular bag IOL implantation are effective in stabilizing the blood-ocular barrier. PMID- 1593428 TI - Scanning electron microscopic study of modern silicone intraocular lenses. AB - Silicone, as manufactured today, appears to be a biocompatible material. The safety and efficacy of silicone lenses are primarily related to the intraocular lens (IOL) design. We compared the edge finish of two three-piece polypropylene loop foldable silicone IOL designs (Allergan Medical Optics) and three one-piece designs (Staar Surgical Co., CooperVision-Cilco). Except for an early Staar one piece design, all lenses including the more recent Staar lenses had acceptably smooth edges with minimal molding flash. PMID- 1593429 TI - Fibrinous reaction on implanted intraocular lenses. A comparison of conventional PMMA and heparin surface modified lenses. AB - We studied the fibrinous reaction after intraocular lens (IOL) implantation in the posterior chamber of cynomolgus monkeys. In 50% of the eyes, we implanted an IOL made of conventional poly-(methyl methacrylate) (PMMA); in the remaining eyes we implanted a PMMA IOL with a heparin modified surface. Two, 4, 8, and 18 weeks after surgery the eyes were examined by slitlamp for fibrinous reactions on and around the IOL surface. At weeks 4, 8, and 18 there was a marked decrease in fibrinous reaction in the eyes with a heparin surface modified IOL. The results of this study accord with earlier findings that heparin surface modification improves the biocompatibility of the IOL. PMID- 1593430 TI - Compatibility of intraocular lenses with blood and connective tissue cells measured by cellular deposition and inflammatory response in vitro. AB - Injection molded poly(methyl methacrylate) (IM-PMMA), lathe-cut PMMA (LC-PMMA), heparin surface modified PMMA (HSM-PMMA), silicone, and polyhydroxyethyl methacrylate (polyHEMA) intraocular lenses (IOLs) were incubated with platelets, granulocytes, mouse macrophage-like RAW 264.7 cells and mouse fibrosarcoma L929 cells to examine their compatibility. The number of cells attached to the IOL was counted after the central IOL area (0.04 mm2) was photographed with an inverted light microscope. Cell morphology was examined by scanning electron microscopy (SEM). More platelets and granulocytes were attached to the IM-PMMA and silicone IOLs than to the HSM-PMMA and polyHEMA IOLs (P less than .05). RAW 264.7 and L929 cells grew on PMMA-based and silicone IOLs, whereas HSM-PMMA and polyHEMA IOLs did not support an abundant growth of these cells. Granulocytes were incubated with the IOLs in the presence of Luminol and the generation of chemiluminescence was measured. Poly(methyl methacrylate)-based IOLs caused granulocytes to release significant amounts of oxygen radicals, while the polyHEMA IOL was almost inactive in stimulating granulocytes. Silicone and HSM-PMMA IOLs showed an intermediate level of stimulating activity. The light intensity reached a peak within 14 minutes with the IM-PMMA IOL, and in about 18 minutes with the other IOLs. Our results suggest that IOL hydrophilicity prevents attachment of cells and that a hydrophilic, soft surface can discourage granulocyte stimulation. PMID- 1593431 TI - Long-term stability of heparin-surface-modified intraocular lenses in vivo. AB - In vivo long-term stability of intraocular lens surfaces, modified by immobilized heparin, was studied. Lenses were implanted in the anterior chamber of rabbits and analyzed for surface concentration of heparin after varying periods of time up to two years. A new method using adsorption of 125iodine-labeled protamine was developed for quantitative measurements of immobilized heparin. Another assay, based on a monoclonal antibody against heparin, was also included. The study showed that surface-immobilized heparin did not degrade or desorb to any measurable degree during a two-year follow-up. PMID- 1593432 TI - Evaluation of 200 consecutive IOGEL 1103 capsular-bag lenses implanted through a small incision. AB - We evaluated 200 consecutive IOGEL 1103 capsular bag intraocular lenses. We performed a 5 to 6 mm capsulorhexis and inserted the intraocular lens (IOL) through a 3.5 to 4.0 mm scleral tunnel with a Faulkner folder. Twenty-two cases were combined with trabeculectomy and ten with keratoplasty using a temporary keratoprosthesis. Mean follow-up was six months. The implant centered well and resisted capsular shrinkage. Iris touch to the optic was rare and did not provoke persistent pigment dispersion. In one third of the cases a cleft was discernible between the posterior convex IOL surface and the extended capsule despite thorough aspiration of viscoelastic and debris from the retrolental space. In 8% of cases, white flakes of unknown origin were observed at the IOL-capsule interface. In cases associated with pre-existing iritis or intraoperative iris trauma (iris manipulation, iridectomy, or synechiolysis in glaucoma patients), fibrin exudation as well as iridocapsular synechial formation and macrophage precipitation often ensued. Cellular precipitates, as evaluated by biomicroscopy and specular microscopy, were less pronounced and more transient than on poly(methyl methacrylate) IOLs. Best case visual acuity results were comparable to those with conventional implants; all eyes attained 20/40 or better and 97% achieved 20/25 or better. The 1103 was easier to implant through a capsulorhexis opening and suited the dimensions of the capsular bag better than the PC-12 model. PMID- 1593433 TI - Risk factors for complications following pediatric epikeratoplasty. AB - We studied the prevalence and types of complications that occurred in children treated with epikeratoplasty to identify risk factors. A review of the clinical records of 88 consecutive patients (106 eyes; 114 procedures) revealed that no complications occurred in 58 grafts (54%). Refractive complications (refractive error greater than 3.00 diopters spherical equivalent from emmetropia or astigmatism greater than 3.00 diopters) occurred in 30 eyes (28%). Medical complications occurred in 22 eyes (19%); these included epithelial defects (14 grafts), interface opacities (six grafts), graft vascularization (eight grafts), graft infection (two grafts), graft necrosis (five grafts), graft haziness (four grafts) or opacification (11 grafts), and graft dehiscence (three grafts). Eleven grafts (10%) were removed and five eyes received new grafts. Epikeratoplasty in children will be more successful if risk factors such as patient age less than one year, microcornea, corneal endothelial cell dysfunction, mental retardation, and combining the procedure with cataract surgery are avoided. PMID- 1593434 TI - Prediction of pseudophakic anterior chamber depth with the newer IOL calculation formulas. AB - Five methods for predicting pseudophakic anterior chamber depth (ACD) by five previously described intraocular lens power calculation formulas (Binkhorst II, Lepper and Trier, Holladay et al., Sanders-Retzlaff-Kraff (SRK/T), Olsen et al.) were evaluated in a series of 640 patients with a posterior chamber lens implant. Significant differences in formula performance were found in unusually short and long eyes. High errors were found in long eyes with the Lepper and Trier formula, the Holladay formula, and the SRK/T method. The highest accuracy was found with the Binkhorst formula and our previously described linear regression formula which expresses the pseudophakic ACD as a function of the average pseudophakic ACD for a given lens style, the preoperative ACD, and the axial length. The use of the preoperative ACD in combination with the axial length for the prediction of the pseudophakic ACD can therefore be expected to improve the accuracy of IOL power calculation. PMID- 1593435 TI - Optical performance of decentered monofocal intraocular lenses. AB - A model eye water cell was used to evaluate the optical performance of biconvex, meniscus, and plano-convex (spheric and aspheric) monofocal poly(methyl methacrylate) intraocular lenses when the lenses were centered and when they were decentered 1 mm and 2 mm. Resolution, induced astigmatism, and modulation transfer function measurements were performed for all lenses with the more convex surface of the lens oriented toward the incident light. The same measurements were performed for the plano-convex and meniscus lenses in the reverse orientation. The lens shapes least affected by decentration were the biconvex and spheric plano-convex with the convex surface oriented toward the incident light. When centered, the aspheric plano-convex lenses had the best overall contrast performance based on the modulation transfer function measurements. However, once decentered the performance of the aspheric lenses approached that of the meniscus lenses in the reverse orientation, the lens shape which had the worst performance. PMID- 1593436 TI - Optical performance of the super-reversed intraocular lens. AB - We compared the aniseikonia, Seidel aberrations, spot diagrams, and peripheral refractive power errors of a schematic eye with a super-reversed intraocular lens (IOL) and with conventional IOLs. The results did not indicate that the super reversed IOL performs better optically than the other IOLs, primarily because of its poorer on-axis image performance. However, this disadvantage can be overcome by aspherizing the super-reversed IOL. PMID- 1593437 TI - Surgical outcome of phacoemulsification combined with the Pearce trabeculectomy in patients with glaucoma. AB - The safety and efficacy of phacoemulsification and posterior chamber lens insertion combined with the Pearce trabeculectomy (PE/PCL/P-TRX) in patients with coexistent cataract and glaucoma was evaluated retrospectively. The Pearce trabeculectomy is a form of nonfiltration glaucoma surgery in which an inner block containing trabecular meshwork is excised under a scleral-pocket incision which is closed tightly. Thirty consecutive eyes sustained a reduction of mean intraocular pressure from 21.0 +/- 4.4 mm Hg to 16.6 +/- 3.3 mm Hg after PE/PCL/P TRX at one year (P less than .001). The average number of glaucoma medications used was reduced from 1.9 to 0.8 postoperatively. At one year, 60% (18 of 30) of eyes treated with PE/PCL/P-TRX had intraocular pressures less than 21 mm Hg without medications. PMID- 1593438 TI - Preoperative pupil fatigue. AB - Pupils are frequently dilated on the day before cataract surgery and for retinal detachment surgery so the fundus can be examined. This may, however, interfere with pupil mydriasis on the day of surgery. This study looked at the effect of pupil dilation with tropicamide 1% and with cyclopentolate 1% on pupil mydriasis 24 hours later, using phenylephrine 10% and cyclopentolate 1%, in 40 cataract patients. The pupils dilated with cyclopentolate one day previously demonstrated a mean reduction in subsequent mydriasis of 0.73 mm compared with pupils that had been dilated with tropicamide (P less than .0001). The magnitude of this difference was not related to the patient age (P = .12) or to iris color (P = .21). If it is necessary to dilate pupils on the day before surgery, tropicamide 1% rather than cyclopentolate 1% should be used, as it is less likely to interfere with the pupil mydriasis produced with cyclopentolate 1% and phenylephrine 10% on the day of surgery. PMID- 1593439 TI - Postoperative capsular bag distension. AB - Seven cases of capsular bag distension following capsulorhexis and phacoemulsification with posterior chamber intraocular lens insertion are presented. The proposed physiological mechanism, associated consequences, and complications and treatment are presented. PMID- 1593440 TI - Irrigation/aspiration handpiece with changeable tips for cortex removal in small incision phacoemulsification. AB - Cortex removal, especially at the 12 o'clock position, is more difficult with small incision phacoemulsification than with planned extracapsular cataract extraction. In this study an irrigation/aspiration handpiece with changeable tips was used for cortex removal in a large, unselected, consecutive series of small incision phacoemulsification procedures. The instrument provided a safe, effective, and economical method of cortex removal. PMID- 1593441 TI - Consultation section. A 54-year-old female had a Choyce-style anterior chamber lens implanted in the right eye. PMID- 1593442 TI - Cellular invasion on hydrogel and PMMA implants. PMID- 1593443 TI - Both ATP and the peptide VIP are inhibitory neurotransmitters in guinea-pig ileum circular muscle. AB - 1. Intracellular membrane potential recordings were made from circular smooth muscle cells of the guinea-pig ileum in the presence of atropine (1 microM) and nifedipine (0.1 microM) at 30 degrees C. 2. Perfusion with adenosine triphospate (ATP, 100 microM) and vasoactive intestinal peptide (VIP, 2 microM) resulted in membrane hyperpolarizations of 6.4 +/- 0.3 and 6.8 +/- 0.3 mV, respectively. Picospritzes of ATP (10 mM in pipette) and VIP (100 microM in pipette) resulted in membrane hyperpolarizations of 6.9 +/- 0.4 and 6.3 +/- 0.4 mV, respectively. 3. The ATP-induced hyperpolarizations were antagonized by alpha, beta-methylene ATP desensitization (100 microM for 30 min) and the ATP antagonist Reactive Blue 2 (200 microM), but were unaffected by the VIP antagonist VIP 10-28 (1 microM). 4. The VIP-induced hyperpolarizations were antagonized by VIP 10-28, but unaffected by alpha, beta-methylene ATP desensitization and Reactive Blue 2. 5. A single pulse of transmural nerve stimulation (2 ms, 15 mA) resulted in an inhibitory junction potential (IJP) that reached a maximal amplitude of 12.9 +/- 0.5 mV at 378 +/- 20 ms from the stimulus. This fast IJP was abolished by apamin (2 microM) or tetrodotoxin (1 microM), antagonized by alpha, beta-methylene ATP desensitization or Reactive Blue 2, but unaffected by VIP 10-28. 6. In the presence of apamin (1 microM), four pulses of transmural stimulation (2 ms, 20 Hz, 15 mA) resulted in an IJP that reached a maximal amplitude of 4.8 +/- 0.2 mV at 1.4 +/- 0.1 s from the stimulus. This slow IJP was antagonized by tetrodotoxin (1 microM) or VIP 10-28 (1 microM), augmented by Reactive Blue 2 (200 microM), and unaffected by alpha, beta-methylene ATP desensitization. 7. These findings provide evidence that both ATP and VIP are inhibitory neurotransmitters in the circular muscle layer of the ileum and that ATP may be the neurotransmitter responsible for the fast IJP and VIP the neurotransmitter responsible for the slow IJP. PMID- 1593444 TI - Properties of a cell volume-sensitive potassium conductance in isolated guinea pig and rat hepatocytes. AB - 1. Whole-cell voltage clamp and intracellular recording techniques were used to study the increase in K+ conductance that accompanies swelling in isolated guinea pig and rat hepatocytes in short-term culture at 37 degrees C. 2. Swelling was induced (i) by the application of pressure (15 cmH2O) to the shank of the patch pipette, (ii) by exposing the cells to hypotonic solutions and (iii) as a consequence of leakage of electrolyte from an intracellular microelectrode. 3. Applying pressure to the patch pipette caused a large outward current (approximately 600 pA) to develop in guinea-pig hepatocytes voltage clamped to 0 mV. This current reversed direction at -86 mV, close to the reversal potential for K+, EK (-93 mV), and is attributable to the activation of a K+ conductance. 4. Spectral analysis of current noise during this response suggested a single channel conductance of 7 pS, though this may well be an underestimate. The power spectrum could be fitted by the sum of two Lorentzian components, with half-power frequencies of 7 and 152 Hz. Seventy per cent of the variance was associated with the lower frequency component. 5. The steady-state current-voltage relationship for guinea-pig hepatocytes, as determined by whole-cell recording, was linear over the range -70 to +40 mV both before and during the increase in K+ conductance induced by swelling. 6. Confirming earlier work, intracellular recording using microelectrodes filled with 1 M-potassium citrate sometimes resulted in a slow hyperpolarization and a large rise in input conductance. These changes are also attributable to an increase in K+ conductance as the cell swelled because of leakage from the electrode. 7. Application of hypotonic external solutions during intracellular recording caused hyperpolarization and an increase in conductance. Conversely, hypertonic solution evoked depolarization and a fall in conductance in partly swollen cells. 8. The volume-activated K+ conductance was reversibly blocked by cetiedil, which caused half-maximal inhibition at 2.3 microM. Bepridil, quinine and barium were also effective, with IC50s (concentrations giving 50% maximal inhibition) of 2.7, 12 and 67 microM respectively. 9. Much greater concentrations of cetiedil and bepridil (IC50 approximately 1 mM and 77 microM respectively) were required to inhibit the loss of K+ which follows the application of angiotensin II (100 nM) to guinea-pig hepatocytes, and which occurs via Ca(2+)-activated K+ channels. Our evidence suggests that the activation of K+ channels by cell swelling is Ca2+ independent.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593445 TI - In vitro studies of prolonged synaptic depression in the neonatal rat spinal cord. AB - 1. Synaptic transmission between dorsal root afferents and alpha-motoneurones was studied in the in vitro hemisected spinal cord preparation isolated from neonatal rats. 2. Repetitive stimulation of the dorsal roots depressed the monosynaptic reflex recorded from the homologous ventral roots. The depression developed within the first five to six pulses in a stimulus train and stabilized at a plateau-like level for many seconds of stimulation. 3. The magnitude of the reflex depression depended on the stimulation interval and was capable of reducing the reflex to 17% of its undepressed control during 5 Hz stimulus trains. Complete recovery from depression was obtained at stimulation intervals greater than or equal to 30 s. 4. Monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly after reduction of the activity in polysynaptic pathways by addition of mephenesin to the bathing media. These EPSPs exhibited a prolonged, frequency-dependent synaptic depression. The depression reduced the amplitude of the EPSP to 25% of the undepressed control during 5 Hz stimulus trains, and was alleviated completely at stimulus interval greater than or equal to 60 s. 5. The prolonged EPSP depression was not altered by blockade of glycinergic and type-A gamma-aminobutyric acid (GABAA-ergic) receptors underlying postsynaptic inhibition in the spinal cord. Injection of current steps to motoneurones before and during the prolonged depression revealed similar values of the membrane time constant and input resistance. These excluded changes in the passive properties of the motoneurone membrane as an explanation for the observed synaptic depression. 6. Extracellular recordings of terminal potentials and their accompanying synaptic fields from motor nuclei in the ventrolateral cord revealed that the frequency-dependent depression in the synaptic fields was not preceded by any detectable changes in the amplitude or the shape of the terminal potential, suggesting that the depression cannot be attributed to impairment of action potential invasion to the afferent terminals. 7. Reduction of the basic level of transmitter release in the spinal cord by increasing the Mg2+/Ca2+ ratio of the bathing solution or by application of 2 microM of L(-)baclofen markedly diminished the synaptic potential depression at all the stimulation intervals tested in this study. Recovery from depression was evident for stimulation intervals greater than or equal to 5 s. Under these conditions, short tetanic trains (5 pulses at 25 Hz) revealed a substantial facilitation and potentiation of the EPSPs. 8. We suggest that prolonged depression of synaptic potentials in the neonatal rat reflects decreased transmitter output from the activated afferent terminals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593446 TI - Influence of temperature on the response time of mitochondrial oxygen consumption in isolated rabbit heart. AB - 1. In this study we determined the temperature dependence of the mean response time of cardiac mitochondrial oxygen consumption following steps in metabolic demand. Metabolic demand was altered by stepwise changes in heart rate or in left ventricular volume at 20 and 28 degrees C. 2. Ten isolated rabbit hearts were perfused with Tyrode solution at constant oxygen tension and constant arterial flow. A balloon was inserted in the left ventricle and developed pressure was measured. Coronary venous oxygen tension was measured continuously with a Clark type oxygen electrode. 3. The mean response time of mitochondrial oxygen consumption is defined as the first statistical moment of the impulse response function. This mean response time of mitochondrial oxygen consumption, following the change in metabolic demand, is calculated from the measured mean response time for the change in coronary venous oxygen tension by subtracting the transport time resulting from diffusion and convective transport in the blood vessels. The transport time is obtained from a model for oxygen transport developed previously. Experimental data, necessary for the model calculation, were obtained from measurement of the coronary venous oxygen tension transients following stepwise changes either in arterial oxygen tension or perfusion flow. 4. The calculated mean response times of mitochondrial oxygen consumption were 26.9 +/- 3.0 s (mean +/- S.E.M.) at 20 degrees C and 14.9 +/- 1.0 s at 28 degrees C. The mean response times of mitochondrial oxygen consumption did not differ significantly for steps in heart rate and in left ventricular volume and between upward and downward steps. 5. We suggest that intracellular calcium concentration is not the sole regulator of mitochondrial oxygen consumption in the isolated rabbit heart, since steps in heart rate and in left ventricular volume showed the same time course of oxygen uptake. 6. The mean response time of mitochondrial oxygen consumption obtained in the isolated rabbit heart at 20 degrees C did not differ significantly from the mean response time of mitochondrial oxygen consumption of isolated rabbit papillary muscle. After combining our data with previously published data on empty beating hearts at 37 degrees C, a Q10, which is the factor by which the mean response time of mitochondrial oxygen consumption increases per 10 degrees C decrease in temperature, of 2.1 was calculated. PMID- 1593447 TI - Imaging of intracellular calcium in rat anterior pituitary cells in response to growth hormone releasing factor. AB - 1. Changes in intracellular ionized calcium [Ca2+]i induced by human growth hormone releasing factor (hGRF) were analysed by quantitative fluorescent microscopy using a dual-wavelength, ratiometric video imaging system and low light level charge-coupled device (CCD) camera visualizing Fura-2 in dispersed male rat anterior pituitary cells. 2. In cells responding to hGRF, spontaneous basal oscillations in [Ca2+]i were frequently observed, and these were usually characterized by a gradient of [Ca2+]i localized in the subplasmalemmal region of the cell. 3. Of the cells which responded to hGRF, the peptide evoked a rise in [Ca2+]i, especially in the region of the subplasmalemma. Continuous application of 10 nM-hGRF produced several different temporal patterns of the [Ca2+]i response which were not attributable to spatial response profiles. A sustained rise in [Ca2+]i was the most common type of response to hGRF (44% of the cells examined). 4. One-third of the cells responding to 10 nM-hGRF showed spontaneous basal [Ca2+]i oscillations ranging from 100 to 500 nM. Mean values of basal and 10 nM-hGRF-induced [Ca2+]i of these cells were 81 +/- 11 nM (mean +/- S.E.M., n = 27) and 560 +/- 47 nM (n = 27) respectively. There was no significant correlation between basal [Ca2+]i and the hGRF-induced [Ca2+]i increase, nor was there any consistent correlation with regard to the spatial response profile. 5. Application of 2 mM-Co2+ abolished the hGRF-induced rise in [Ca2+]i. Quantitative analysis of this effect, performed by comparing the mean [Ca2+]i evoked during the application of hGRF with and without Co2+, respectively, also showed significant inhibition of the hGRF-induced rise in [Ca2+]i by the application of Co2+ (P less than 0.001). 6. The hGRF-induced rise in [Ca2+]i was completely suppressed by replacing extracellular Na+ with impermeant molecules such as mannitol. The onset and offset of suppression was as rapid as that induced by Co2+. Quantitative analysis showed significant inhibition of the hGRF-induced rise in [Ca2+]i by Na+ replacement (P less than 0.01). 7. Tetrodotoxin, a potent blocker of voltage-sensitive Na+ channels (5 and 20 microM), did not affect the hGRF-induced rise in [Ca2+]i. 8. Extracellular application of the membrane permeable dibutyryl cyclic AMP (DBcAMP) to elevate intracellular levels of cyclic AMP caused a large rise in [Ca2+]i, which was dependent on extracellular Na+ and was abolished by 2 mM-Co2+ applied in the bath.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593448 TI - Electrophysiology of a slow (0.5-4 Hz) intrinsic oscillation of cat thalamocortical neurones in vivo. AB - 1. Electrophysiologically identified thalamocortical neurones have been intra- and extracellularly recorded in acutely prepared cats, under different anaesthetic conditions. 2. A slow (0.5-4 Hz) membrane potential oscillation was observed in thalamocortical cells recorded in motor, sensory, associational and intralaminar thalamic nuclei. The oscillation consisted of rhythmic low-threshold spikes alternating with after-hyperpolarizations. 3. About 80% of the neurones with intact cortical connections were set into the slow oscillatory mode by bringing their membrane potential to between -68 and -90 mV. The oscillation did not depend upon the occurrence of fast action potentials and did not outlast the imposed hyperpolarization. 4. Anatomical or functional disconnection from related cortical areas resulted in a membrane potential hyperpolarization of about 9 mV and in the occurrence of spontaneous slow oscillations in virtually all recorded neurones. The intrinsic nature of the phenomenon was supported by the lack of rhythmic postsynaptic potentials as the cells were prevented from oscillating by outward current injection. 5. In contrast with other thalamic nuclei, the slow oscillation has not been observed in anterior thalamic neurones despite their having similar basic electrophysiological properties. 6. Barbiturate administration suppressed the slow oscillatory mode, an effect accompanied by a decrease in the membrane input resistance. 7. Multiunit recordings of spontaneously oscillating cells showed epochs characterized by phase-related firing. This synchronous discharge was paralleled by a clear-cut build-up of field potentials in the frequency range of electroencephalogram slow or delta waves. 8. These results demonstrate that the majority of thalamocortical neurones are endowed with electrophysiological properties allowing them to oscillate at 0.5-4 Hz, if they have a membrane potential more negative than -65 mV and a high input resistance. Such a condition is physiologically achieved in the deepest stages of electroencephalogram-synchronized sleep, as a result of brain stem thalamic as well as cortico-thalamic deafferentation. We postulate a thalamic contribution in the genesis of electroencephalogram delta waves during slow wave sleep, once independently oscillating thalamocortical cells become in phase. PMID- 1593449 TI - Delayed rectifier potassium channels in canine and porcine airway smooth muscle cells. AB - 1. In order to define the ion channels underlying the inactivating, calcium insensitive current in airway smooth muscle cells, unitary potassium currents were recorded from canine and porcine trachealis cells, and compared with macroscopic currents. On-cell and inside-out single-channel currents were compared with whole-cell recordings made in dialysed cells. 2. Depolarizing voltage steps evoked outward unitary currents. In addition to a large conductance, calcium-activated potassium channel (KCa), a lower conductance potassium channel was identified. This channel has a conductance of 12.7 pS (on cell; 1 mM-K+ in the pipette). 3. The lower conductance channel (Kdr) was not sensitive to cytosolic Ca2+ concentration and unitary current openings occurred following a delay after the voltage step. The time course of activation of the current composed of averaged single-channel events was very similar to that of the whole-cell, delayed rectifier potassium current (IdK), recorded under conditions of low intracellular calcium (Kotlikoff, 1990). 4. Kdr channels also inactivated with kinetics similar to those of the macroscopic current. Averaged single-channel records revealed a current that inactivated with kinetics that could be described by two exponentials (tau 1 = 0.14 s, tau 2 = 1.1 s; at 5 mV). These values corresponded well with previously determined values for time dependent inactivation of IdK. Inactivation of Kdr channels was markedly voltage dependent, and was well fitted by a Boltzmann equation with V50 = -53 mV; this was similar to measurements of the macroscopic current, although the V50 value was shifted to more positive potentials in whole-cell measurements. When only the inactivating component of the macroscopic current was considered, the voltage dependence of inactivation of the single-channel current and macroscopic current were quite similar. 5. Single-channel kinetics indicated that Kdr channels occupy one open and two closed states. The mean open time was 1.7 ms. Inactivation results in a prominent increase in the long closed time, with little effect on the mean open time or short closed time. 6. The Kdr channel was not blocked by tetraethylammonium (TEA; 1 mM), charybdotoxin (ChTX; 100 nM) or glibenclamide (20 microM), but was blocked by 4-aminopyridine (4-AP; 1 mM). Similarly, 4-AP blocked the inactivating component of the macroscopic current, but a non-inactivating current remained. KCa currents were blocked by TEA (0.5-1 mM) and charybdotoxin (40 nM), but were insensitive to to 4-AP (1 mM) and glibenclamide (20 microM).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593450 TI - Volume status influences atrial peptide-induced water conductivity changes in leopard frog mesenteric capillaries. AB - 1. Three sets of North American leopard frogs (Rana pipiens) were housed on damp sand (DS, n = 19), in fresh water (FW, n = 19), or with free access to both damp sand and fresh water (FA, n = 23) for a period of 5-6 days. At the end of this period pithed frogs were prepared for measurement of capillary hydraulic conductivity and samples of whole-blood, lymph and body cavity fluid were collected for measurement of haematocrit and protein content. 2. To measure hydraulic conductivity (Lp), individual capillaries of the mesenteries of the three groups were cannulated and perfused with a minimum of two, and a maximum of three, frog Ringer solutions. The first solution, common to all experiments, contained dialysed bovine serum albumin (BSA) at a concentration of 10 mg ml-1. The second and third solutions also contained either 10 nM-atrial peptide (AP) or 1 microM-sodium nitroprusside (SNP). Lp was determined from measurements of fluid filtration rate at a minimum of two different capillary pressures (Michel, Mason, Curry, Tooke & Hunter, 1974). 3. In vessels from damp sand-stored frogs (DS), the paired Lp in the presence of 10 nM-atrial peptide (Lp, AP) was 3.2 +/- 0.4-fold higher than Lp, BSA (n = 25). By contrast, in the FW group, Lp, AP did not differ significantly from Lp, BSA (Lp, AP-FW/Lp, BSA = 1.3 +/- 0.2; n = 23). In frogs given free access to water and dry terrain the response to atrial peptide was similar to that observed in the DS group (Lp, AP-FA/Lp, BSA = 3.6 +/- 07; n = 23). Thus, storage in fresh water appears to have inhibited the acute Lp response to atrial peptide observed in vessels from the FA or DS animals. 4. Atrial peptide and sodium nitroprusside elevate intracellular cyclic GMP levels by membrane receptor-dependent and -independent processes, respectively. No difference was observed in the Lp response to 1 microM-perfusate sodium nitroprusside (Lp, SNP) in DS (n = 7), FW (n = 8) or FA (n = 30) frogs (Lp, SNP/Lp, BSA ratios were 3.5 +/- 1.5-, 2.7 +/- 0.8- and 2.6 +/- 0.5-fold, respectively). Thus, the Lp response to sodium nitroprusside was not affected by storage conditions. 5. The mean haematocrit of skin blood samples from the DS groups was 26.5 +/- 1.0% (+/- S.E.M.) compared to 19.1 +/- 1.2% from the FW groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593451 TI - Directional sensitivity of human periodontal mechanoreceptive afferents to forces applied to the teeth. AB - 1. Single-unit impulse activity from thirty-eight mechanoreceptive afferent fibres was recorded in the human inferior alveolar nerve using tungsten microelectrodes. All afferents responded to mechanical stimulation of the teeth and most likely supplied periodontal mechanoreceptors. 2. All afferents showed their highest sensitivity to forces applied to a particular tooth (the lower incisors, the canine or the first premolar). Forces with 'ramp-and-hold' shaped profiles of similar magnitudes were applied to that tooth in the following six directions: lingual, labial, mesial and distal in the horizontal plane, and up and down in the axial direction of the tooth. Both static and dynamic response components were analysed. 3. All afferents were 'slowly adapting' since they discharged continuously in response to static forces in at least one stimulation direction. Twenty-five afferents (66%) were spontaneously active in the sense that they showed an on-going discharge in the absence of external stimulation. 4. Diverse receptive fields were observed. Most afferents (74%) responded to static forces in two or three of the four horizontal directions. Likewise, all units showed excitatory responses to axial loading with a majority (74%) responding in one of the two axial directions and the remainder in both axial directions. Spontaneously active afferents generally decreased their discharge rate when stimulated in directions opposite to the directions exciting the afferent. With regard to population responses, approximately half of the afferents showed excitatory responses to each stimulus direction except for downwards, in which 86% responded. 5. Twenty-three afferents (61%) exhibited the strongest response to forces in one of the horizontal directions. Of those, a majority were most responsive to the lingual direction (52%) and some to the labial direction (30%). Accordingly, the discharge rates during force application averaged over the whole afferent sample were highest in these directions. Of the remaining afferents, most responsive to one of the axial directions, 60% showed their strongest responses to forces in the downward direction. 6. Forty-five per cent of the afferents showed wider receptive fields to the dynamic component of the force stimulation than to the static. The direction of maximal sensitivity, however, remained the same with few exceptions. 7. It was demonstrated that even though individual periodontal mechanoreceptive afferents provide ambiguous information regarding the direction of a force applied to a tooth, populations of such afferents are well suited to give detailed directional information. It is suggested that such information may play an important role for the control of mastication. PMID- 1593452 TI - Haemodynamic effects of distension of the descending colon in anaesthetized dogs. AB - 1. This study was undertaken to determine whether distension of the descending colon in anaesthetized dogs reflexly affects the heart rate, arterial blood pressure or the left ventricular inotropic state. 2. Experiments were performed on twenty-six dogs, which were anaesthetized with sodium pentobarbitone and artificially ventilated. A segment of the distal descending colon was isolated and was distended with warm Ringer solution at a steady intraluminal pressure. 3. In each animal, distension of the colon caused an increase in heart rate and aortic blood pressure. The response of an increase in heart rate was augmented by preventing changes in aortic blood pressure, and was graded in seven dogs by step increments in the distending pressure. In the same animals, distension of the colon always caused a small increase in left ventricular (dP/dt)max at constant heart rate and aortic blood pressure. 4. In four of the twenty-six dogs, cutting the pelvic nerves did not abolish the observed responses to the distension. In seven of the twenty-six dogs, which included the four animals with sectioned pelvic nerves, cutting the hypogastric nerves completely abolished all the observed responses. 5. In thirteen of the twenty-six dogs, propranolol or bretylium tosylate completely abolished the reflex increases in heart rate and left ventricular (dP/dt)max, and phentolamine or bretylium tosylate abolished the reflex increase in aortic blood pressure. 6. These results showed that distension of the colon reflexly increased the heart rate, arterial blood pressure and left ventricular inotropic state. These reflex responses were mediated by sympathetic effects and their afferent limb involved the hypogastric nerves. PMID- 1593453 TI - Tension responses to joule temperature jump in skinned rabbit muscle fibres. AB - 1. Joule temperature jumps (T-jumps) from 5-9 degrees C up to 40 degrees C were used to study the cross-bridge kinetics and thermodynamics in skinned rabbit muscle fibres. To produce a T-jump, an alternating current pulse was passed through a fibre 5 s after removing the activating solution (pCa congruent to 4.5) from the experimental trough. The pulse frequency was congruent to 30 kHz, amplitude less than or equal to 3 kV, and duration 0.2 ms. The pulse energy liberated in the fibre was calculated using a special analog circuit and then used for estimation of the T-jump amplitude. 2. The T-jump induced a tri exponential tension transient. Phases 1 and 2 had rate constants k1 = 450-1750 s 1 and k2 = 60-250 s-1 respectively, characterizing the tension rise, whereas phase 3 had a rate constant k3 = 5-10 s-1 representing tension recovery due to the fibre cooling. 3. An increase from 13 to 40 degrees C for the final temperature achieved by the T-jump led to an increase in the amplitudes of phases 1 and 2. After T-jumps to 30-40 degrees C during phase 1, tension increased by 50 80%. During phase 2 an approximately 2-fold tension increase continued. Rate constants k1 and k2 increased with temperature and temperature coefficients (Q10) were 1.6 and 1.7, respectively. 4. To study which processes in the cross-bridges are involved in phases 1 and 2, a series of experiments were made where step length changes of -9 to +3 nm (hs)-1 (nanometres per half-sarcomere length) were applied to the fibre 4 ms before the T-jump. 5. After the step shortening, the rate constant of phase 1 increased, whereas its amplitude decreased compared to those without a length change. This indicates that phase 1 is determined by some force-generating process in the cross-bridges attached to the thin filaments. This process is, most probably, the same as that producing the early tension recovery following the length change. The enthalpy change (delta H) associated with the reaction controlling this process was estimated to be positive (15-30 kJ mol-1). 6. Both the rate constant k2 and the maximal tension achieved at the end of phase 2 were practically independent of the preceding length changes. This means that phase 2 is accompanied by the cross-bridge detachment and reattachment to new sites on the thin filaments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593454 TI - The central projection of electrosensory information in the platypus. AB - 1. This is the first detailed description of the projection to the cerebral cortex of afferent information coming from electroreceptors in the bill of the platypus, Ornithorhynchus anatinus. 2. In animals anaesthetized with chloralose, with the bill immersed in tap water, applying a potential difference between plate electrodes on either side of the bill produced large amplitude potentials from the surface of a postero-lateral region of cerebral cortex. Response threshold was 300 microV cm-1, somewhat lower than threshold measured for single identified electroreceptors. Electroreceptor threshold was at least three orders of magnitude lower than threshold of mechanoreceptors to electrical stimuli (Gregory, Iggo, McIntyre & Proske, 1989a). 3. Monopolar stimulation of the bill revealed a crossed projection. The map on the cortical surface had the bill oriented dorso-laterally, its base towards the mid-line, the tip on the lateral edge, pointing slightly forwards. The edge of the bill faced backwards. Electrosensory information coming from the edge of the bill appeared to be much more strongly represented than input from the dorsal surface. 4. Weak electrical and mechanical stimuli applied to the bill both evoked large amplitude potentials from the same region of cortex indicating that there was complete overlap between the regions receiving tactile and electrosensory inputs. 5. Inserting microelectrodes into the deeper layers of cortex revealed burst discharges in single cells and groups of cells in response to weak electrical stimulation of the bill. Activity could be recorded over a range of depths from 0.3 to 4 mm, with the majority of responses coming from cells 1-3 mm deep. Histological examination of lesion sites made at 1.1 mm and at 3 mm suggested that cells in the pyramidal and ganglion layers were involved in generating the activity. 6. Some evidence was obtained for interactions at the level of the cerebral cortex between activity generated by tactile and electrosensory inputs. When electrical and mechanical stimuli were both applied to the bill with an interstimulus interval of less than 25 ms, cortical neuronal responses generated by one stimulus were completely suppressed by the other. However no evidence was obtained of a direct convergence at the level of the cortex between the two modalities. 7. Cortical activity could be evoked in response to rapidly changing voltage fields. This observation, together with our earlier finding of a high rate sensitivity of the receptors, emphasizes the high dynamic sensitivity of the system. 8. It is concluded that the electrosensory system of the platypus is closely associated with the sense of touch.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593455 TI - Electrical behaviour of myenteric neurones in the gastric antrum of the guinea pig. AB - 1. Intracellular microelectrodes were used to study the electrical behaviour of ganglion cells in the myenteric plexus of the antrum of the guinea-pig stomach. In the absence of any information on antral myenteric neurones, the aim was to characterize the electrical behaviour and identify biophysical properties of the neurones that could be related to specialized organization of the neural microcircuits in this physiologically important division of the stomach. 2. Myenteric neurones in the gastric antrum were classified into four subtypes based on electrophysiological properties. These were gastric I, II, III and AH/type 2 neurones. Gastric I neurones were characterized by repetitive spike discharge during intraneuronal injection of depolarizing current, by higher input resistances and by lower resting membrane potentials than the other cell types. Gastric II neurones did not discharge repetitively. They discharged one or two spikes only at the beginning of depolarizing current pulses. Gastric III neurones did not discharge action potentials in response to depolarizing pulses. These neurones had higher membrane potentials and lower input resistances than the other types. A fourth type of neurone discharged one or more spikes during depolarizing current pulses and had long-lasting hyperpolarizing after-potentials associated with the spikes. The behaviour of these neurones was like AH/type 2 neurones found elsewhere in the enteric nervous system. 3. Action potentials in gastric I and II neurones were abolished by tetrodotoxin. Spikes of the AH/type 2 cells were not abolished by tetrodotoxin due to a calcium component of the inward current. Application of tetraethylammonium broadened the spikes. This was reversed by removal of Ca2+ from the bathing medium. 4. The hyperpolarizing after potentials of AH/type 2 neurones were suppressed by removal of Ca2+ from the bathing medium. Treatment with 4-aminopyridine decreased the amplitude and duration of the after-hyperpolarization, whereas tetraethylammonium increased the duration and amplitude of the after-potentials. The hyperpolarizing after potentials were unaffected by apamin. 5. Elevation of cyclic 3',5'-adenosine monophosphate by forskolin resulted in excitation of all AH/type 2 neurones and some of the gastric III cells. Gastric I and II neurones were unaffected. 6. The electrophysiological behaviour of myenteric neurones in the antrum was similar in some respects and different in others from neurones in the gastric corpus and the small and large intestine of the same animal. The differences may reflect distinct organization of the microcircuits for the specialized neural control of the effector functions which characterize the gastric antrum. PMID- 1593456 TI - Dietary restriction sensitizes the rat distal colon to aldosterone. AB - 1. The effects of starvation and undernutrition were assessed on rat colonic electrogenic Na+ absorption in fed controls, 72 h starved and acute undernourished (fed one-third of the control group's daily food intake for up to 9 days). The basal short-circuit currents (Isc) of three segments of rat colon (proximal, mid- and distal), stripped of their external muscle layers were monitored before and during addition of 0.1 mM-mucosal amiloride. The decrease in Isc was used as the measure of the electrogenic Na+ absorption. 2. Acute undernutrition and to a lesser extent 72 h starvation elevated the basal Isc only in the distal colon. The increase was inhibited by amiloride (0.1 mM, mucosal) indicating that it was due to electrogenic Na+ transport. 3. Allowing the 9 days acute undernourished rats to drink 0.9% NaCl failed to prevent the increase in the basal Isc in the distal colon but it was reduced by administration of spironolactone. 4. Adrenalectomy completely abolished the increased basal Isc in the distal colon induced by the 9 day undernutrition. However, the plasma aldosterone levels in the fed and 9 day undernutrition groups were not significantly different. 5. Injection of aldosterone into adrenalectomized rats drinking 0.9% NaCl and which were undernourished for 9 days induced a large increase in their distal colonic Isc which was inhibited by mucosal amiloride. Similar treatment of sham-operated rats on 0.9% NaCl or adrenalectomized control fed rats on 0.9% NaCl had no effect on the distal colonic Isc. 6. The results indicate that acute undernutrition for 9 days makes the distal colonic epithelium more sensitive to the prevailing plasma aldosterone level allowing an enhanced electrogenic Na+ absorptive capacity to be induced. PMID- 1593457 TI - The inositol 1,4,5-trisphosphate pathway mediates cholinergic potentiation of rat hippocampal neuronal responses to NMDA. AB - 1. The cellular mechanism by which acetylcholine (ACh) potentiates neuronal responses to N-methyl-D-aspartate (NMDA) was investigated in CA1 neurones of hippocampal slices using current- and voltage-clamp techniques. 2. Loading cells with 5'-guanylylimidodiphosphate (GppNHp) caused a gradual increase in response to NMDA. Pulses of ACh accelerated this increase. Guanosine 5'-O-(2 thiodiphosphate) (GDP beta S) blocked the potentiating effect of ACh on responses to NMDA. 3. Acute LiCl caused a gradual decrease in the potentiating effect of ACh, while the potentiation was completely prevented by 3 day chronic 6 mequiv/kg (I.P.) LiCl treatment and restored by acute treatment with 10 mM-inositol. 4. Loading cells with a general protein kinase inhibitor, H-7, enhanced the potentiating effect of ACh on responses to NMDA and blocked the effect of ACh on the after-hyperpolarization (AHP). 5. Ultraviolet irradiation of cells loaded with a photolabile inositol 1,4,5-trisphosphate (InsP3) caused a transient increase in responses to NMDA, while penetrating cells with active InsP3 containing pipettes caused a gradual BAPTA-sensitive increase in responses to NMDA. 6. Reducing the rate of InsP3 metabolism, with 2,3-diphosphoglyceric acid (DPG), caused an increase and prolongation of the potentiating effect of ACh, while blocking the InsP3 receptor with heparin prevented the cholinergic potentiation. 7. NMDA, by itself, potentiated subsequent responses to NMDA, an effect that was blocked when [Ca2+]i was chelated with BAPTA. NMDA and ACh were also found to compete in potentiating responses to NMDA. Finally, the cholinergic potentiation was blocked when cells were loaded with BAPTA. 8. We propose that activation of the InsP3 branch of the phosphoinositide pathway potentiated responses to NMDA and that InsP3 exerted this effect by elevating [Ca2+]i. PMID- 1593458 TI - Effect of digital nerve stimuli on responses to electrical or magnetic stimulation of the human brain. AB - 1. Reflexes were elicited in the first dorsal interosseous muscle of seven normal subjects by electrical stimulation of the digital nerves of the index finger at 3 times perceptual threshold while subjects maintained a constant voluntary contraction of the muscle. The average response in the surface-rectified electromyogram (EMG) consisted of an early inhibitory (I1) component followed by a later excitation (E2). 2. Low intensity anodal electrical or magnetic scalp stimuli were given over the motor cortex in order to elicit muscle responses within the period of the I1 and E2 reflex components. 3. Compared with control responses elicited in the absence of digital nerve stimulation, responses to electrical cortex stimulation were suppressed in the I1 period and facilitated during the E2 period of the reflex. In contrast, responses evoked by magnetic stimulation were suppressed during I1 and also for the first 10 ms or so of the E2 response. Magnetically evoked responses were facilitated during the later part of the E2 reflex. 4. Similar effects were seen when the probability of firing of single motor units was studied. 5. In three subjects, small taps were given to the abducted index finger in order to stretch the first dorsal interosseous muscle and evoke reflexes which were of comparable size to the E2 reflex evoked by digital nerve stimulation. In contrast to the experiments in which digital nerve stimuli were given, responses evoked by magnetic stimulation over motor cortex were facilitated at all times during the course of the reflex evoked when the muscle was stretched. 6. We conclude that single electrical stimuli applied to the digital nerves can reduce for a short period the excitability of motor cortex to magnetic stimulation. This occurs at a time when the same stimulus is evoking an excitatory (E2) reflex in the average surface-rectified EMG. PMID- 1593459 TI - Changes in R-R interval at the start of muscle contraction in the decerebrate cat. AB - 1. The effect on R-R interval of a brief hindlimb contraction, elicited by electrical stimulation of L7 ventral roots, was investigated in decerebrate cats. The first series of experiments was performed at both low and high carotid sinus pressure to vary the level of vagal tone. When carotid sinus pressure was elevated to increase vagal tone, contraction commenced 1 s later. 2. The change in R-R interval at low carotid sinus pressure was expressed as the difference between the mean of the five R-R intervals immediately preceding contraction and the mean of the last five R-R intervals at the end of a 5 s contraction. At high carotid sinus pressure, the change was expressed as the difference between the mean of the last five R-R intervals at the end of a 5 s contraction and the mean of five R-R intervals at an equivalent time after raising pressure alone. 3. Hindlimb contraction at low carotid sinus pressure produced a significant reduction in R-R interval from 359 +/- 25 (mean +/- S.E.M. n = 8) to 336 +/- 24 ms (P less than 0.005). At high carotid sinus pressure the response was enhanced with contraction producing a reduction in R-R interval from 474 +/- 45 to 419 +/- 47 ms (P less than 0.001). 4. The shortening of R-R interval produced by hindlimb contraction at high carotid sinus pressure, 55 +/- 8 ms, was significantly greater than that observed at low sinus pressure, 23 +/- 5 ms (P less than 0.001, n = 8, paired t test). This pattern of response was also seen at stimulation frequencies as low as 10 Hz. 5. In a second series of experiments, designed to determine the latency of the cardiac acceleration, the minimum latency between the onset of L7 ventral root stimulation and the end of the first shortened R-R interval was 687 +/- 29 ms (n = 5). 6. Atropine (0.4 mg kg-1, I.V.) prevented a 5 s contraction from producing any change in R-R interval. 7. These results indicate that afferent information originating from receptors in contracting muscles is responsible for producing an immediate shortening of R-R interval, which is mediated by vagal withdrawal. The possibility that the shortening of R-R interval at the start of contraction is linked to a reduction in arterial baroreceptor reflex sensitivity, possibly via inhibitory effects on neurones forming the central pathway of the baroreceptor reflex, is discussed. PMID- 1593460 TI - Changes in the stretch reflex of the human first dorsal interosseous muscle during different tasks. AB - 1. Subjects flexed the interphalangeal joint of the index finger against a lever which was mounted on the shaft of a torque motor. 2. There were two different tasks. In one, the subject attempted to maintain a constant finger position in the face of changing forces, whereas in the other the subject attempted to maintain a constant force while the motor moved the lever. 3. Each of the tasks was interrupted by ramp extensions. These evoked stretch reflexes which were recorded in the first dorsal interosseous (FDI) muscle electromyogram (EMG). 4. Long-latency (55-90 ms) reflex responses were larger during the 'maintain position' task than during the 'maintain force' task, although the ramp extensions began from a similar finger position, a similar flexing force, and with a similar amount of FDI EMG activity. 5. It is concluded that the nature of the task has an effect on the magnitude of the long-latency stretch reflex. PMID- 1593461 TI - Task-dependent changes in the response of human wrist joints to mechanical disturbance. AB - 1. Subjects sat with their right hands in a mould which was attached to the shaft of a servo-controlled motor. 2. There were two different tasks. In one, the subject attempted to maintain a constant wrist flexing force, while the motor imposed flexion-extension movements. In the other, the subject attempted to maintain a constant wrist position while the motor exerted variable flexion extension forces. 3. The 'maintain force' task was punctuated by randomly timed ramp extension movements to test the stretch reflex activity. The 'maintain position' task was punctuated by force changes which were the same as those recorded during the ramp extensions mentioned above. In this way it was possible to test stretch reflexes with the same disturbance during the 'maintain force' and 'maintain position' tasks. 4. When, after some practice, subjects had become good at maintaining the constant force, later components of the stretch reflex (after 40 ms) were found to be smaller than when they were maintaining a constant position. 5. Attempts to maintain a constant position often involved co activation of the wrist extensor muscles. This could be prevented by local anaesthesia of the radial nerve. The long-latency stretch reflex of the flexors was still task dependent after this had been done. 6. The roles of co-activation and of task-dependent reflex responses are discussed. PMID- 1593462 TI - ATP-sensitive K+ channels and cellular K+ loss in hypoxic and ischaemic mammalian ventricle. AB - 1. The contribution of ATP-sensitive K+ (K+ATP) channels to the rapid increase in cellular K+ efflux and shortening of action potential duration (APD) during early myocardial ischaemia and hypoxia remains controversial, because for the first 10 min of ischaemia or hypoxia in intact hearts cytosolic [ATP] remains about two orders of magnitude greater than the [ATP] causing half-maximal blockade of K+ATP channels in excised membrane patches. The purpose of this study was to investigate this apparent discrepancy. 2. During substrate-free hypoxia, total, diastolic and systolic unidirectional K+ efflux rates increased by 43, 26 and 103% respectively after 8.3 min in isolated arterially perfused rabbit interventricular septa loaded with 42K+. APD shortened by 39%. From the Goldman Hodgkin-Katz equation, the relative increases in systolic and diastolic K+ efflux rates were consistent with activation of a voltage-independent K+ conductance. 3. During total global ischaemia, [K+]o measured with intramyocardial valinomycin K(+)-sensitive electrodes increased at a maximal rate of 0.68 mM min-1, which could be explained by a less than 26% increase in unidirectional K+ efflux rate (assuming no change in K+ influx), less than the increase during hypoxia. APD shortened by 23% over 10 min. 4. During hypoxia and ischaemia, cytosolic [ATP] decreased by about one-third from 6.8 +/- 0.5 to 4.3 +/- 0.3 and 4.6 +/- 0.4 mM respectively, and free cytosolic [ADP] increased from 15 to 95 and approximately 63 microM respectively. 5. To estimate the percentage of activation of current through K+ATP channels (IK,ATP) necessary to double the systolic K+ efflux rate (comparable to the increase during hypoxia), K+ efflux during a single simulated action potential was measured by blocking non-K+ currents under control conditions and after IK,ATP was fully activated by metabolic inhibitors. Activation of 0.41 +/- 0.07% of maximal IK,ATP was sufficient to double the systolic K+ efflux rate. The equivalent amount of constant hyperpolarizing current also shortened the APD in the isolated myocytes by 41 +/- 5%, compared to the 39% APD shortening observed during hypoxia in the intact heart. 6. The degree of activation of IK,ATP expected to occur during hypoxia and ischaemia was estimated by characterizing the ATP sensitivity of K+ATP channels in the presence of 2 mM-free Mgi2+ and 0, 10, 100 and 300 microM-ADPi in inside-out membrane patches excised from guinea-pig ventricular myocytes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593463 TI - Adenosine promotes burst activity in guinea-pig geniculocortical neurones through two different ionic mechanisms. AB - 1. The mechanisms of action of adenosine were examined in relay neurones of the dorsal lateral geniculate nucleus (LGND) using in vitro intracellular recording techniques in guinea-pig thalamic slices. 2. Adenosine hyperpolarized LGND relay neurones due to an increase in membrane potassium conductance. The K+ currents generated by near maximal stimulation of adenosine and GABAB receptors were non additive. 3. Blockage of membrane K+ conductances by barium unmasked a second response to adenosine; an outward shift of the current versus voltage relationship negative to -65 mV associated with an increase in membrane input resistance. The beta-adrenoceptor agonist isoprenaline elicited an inward current in the same voltage range, which was inhibited and replaced by an outward current during activation of adenosine receptors. The effects of adenosine were due to a decrease in amplitude and rate of rise of the hyperpolarization-activated cation current, Ih. Maximal reduction by 66% of Ih amplitude occurred near the range of half-activation. 4. Both responses to adenosine were mimicked by the selective A1 receptor agonists N6-cyclopentyladenosine or N6-cyclohexyladenosine, and reversibly blocked by the selective A1 receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine (DPCPX). 5. The decrease in Ih by adenosine may be mediated by an inhibition of adenylyl cyclase activity and hence a decrease in the intracellular level of cyclic AMP, since local application of the adenylyl cyclase inhibitor 2',3'-dideoxyadenosine imitated the decrease in Ih. Local application of the adenylyl cyclase stimulant forskolin or 8-bromo-cyclic AMP resulted in an enhancement in Ih, and forskolin inhibited the action on Ih evoked by N6-cyclopentyladenosine. 6. The adenosine-induced effects interacted with the intrinsic electrophysiological properties of LGND neurones in that (i) the hyperpolarization due to an increase in K+ conductance inhibited single spike firing and promoted calcium-mediated burst discharges, and (ii) the decrease in Ih inhibited the dampening effect on Ca(2+)-mediated rebound activity of beta adrenergic receptor stimulation. 7. It is suggested that during increased levels of extracellular adenosine the response of LGND relay neurones to activating brainstem influences will be depressed, and a pattern of Ca(2+)-mediated burst firing will be favoured. PMID- 1593464 TI - The development of cortico-motoneuronal projections investigated using magnetic brain stimulation in the infant macaque. AB - 1. The effects of magnetic brain stimulation on electromyographic (EMG) activity recorded from arm and hand muscles have been investigated in five infant and six adult macaque monkeys under ketamine sedation. 2. In the adults, brief, short latency EMG responses could be readily evoked with magnetic stimuli of 40-50% of the maximum stimulator output (1.5 T). 3. In a cross-sectional study of five infant macaques, it was difficult to evoke EMG responses in young infants (less than 5 months old). Clear short-latency responses were first evoked in an animal 5.75 months old. This change was accompanied by an increase in the probability of occurrence of the responses. 4. In a longitudinal study of two infant monkeys over a period ranging from 2.5 to 14.5 months of age we found that clear short latency responses were first evoked at 4 and at 5.5 months, respectively. In both animals there was a steady fall in response threshold which reached the adult range at 6.5 and 8 months, respectively. EMG responses in animals older than 8 months were indistinguishable from those in adults. 5. In the longitudinal study we also noted that the latency of EMG responses to magnetic brain stimulation declined with age. Since there were no comparable changes in the peripheral conduction time in these animals, we attribute this result to a decrease in central conduction time. 6. Parallel behavioural observations of the natural behaviour of the same animals within a colony indicated that mature precision movements of the fingers were not used until 5-6 months of age. 7. In two adult monkeys, the latency of EMG responses evoked in the extensor digitorum and first dorsal interosseous muscles by direct stimulation of the corticospinal tract, via electrodes implanted in the medullary pyramids, was found to be 0.7-1.7 ms shorter than that of responses evoked by magnetic stimuli. It is argued that at least the earliest component of these latter responses is conducted over the cortico-motoneuronal pathway. 8. The mechanisms likely to contribute to the late appearance of EMG responses to brain stimulation are discussed. One of these is probably the establishment of mature cortico-motoneuronal connections, which are not present at birth. PMID- 1593465 TI - Cytosolic calcium and myofilaments in single rat cardiac myocytes achieve a dynamic equilibrium during twitch relaxation. AB - 1. Single isolated rat cardiac myocytes were loaded with either the pentapotassium salt form or the acetoxymethyl ester (AM) form of the calcium sensitive fluorescent probe, Indo-1. The relationship of the Indo-1 fluorescence transient, an index of the change in cytosolic calcium [Ca2+]i concentration, to the simultaneously measured cell length during the electrically stimulated twitch originating from slack length at 23 degrees C was evaluated. It was demonstrated that even if the Ca2+ dissociation rate from Indo-1 was assumed to be as slow as 10 s-1, the descending limb ('relaxation phase') of the Indo-1 fluorescence transient induced by excitation under these conditions is in equilibrium with the [Ca2+]i transient. Additionally, the extent of Indo-1 loading employed did not substantially alter the twitch characteristics. 2. A unique relationship between the fluorescence transient and cell length was observed during relaxation of contractions that varied in amplitude. This was manifest as a common trajectory in the cell length vs. [Ca2+]i phase-plane diagrams beginning at the time of cell relengthening. The common trajectory could also be demonstrated in Indo-1 AM loaded cells. The Indo-1 fluorescence-length relation defined by this common trajectory is steeper than that described by the relation of peak contraction amplitude and peak fluorescence during the twitch contractions. 3. The trajectory of the [Ca2+]i-length relation elicited via an abrupt, rapid, brief (200 ms) pulse of caffeine directly onto the cell surface or by 'tetanization' of cells in the presence of ryanodine is identical to the common [Ca2+]i-length trajectory formed by electrically stimulated contractions of different magnitudes. As the [Ca2+]i and length transients induced by caffeine application or during tetanization in the presence of ryanodine develop with a much slower time course than those elicited by electrical stimulation, the common trajectory is not fortuitous, i.e. it cannot be attributed to equivalent rate-limiting steps for the decrease of [Ca2+]i and cell relengthening. 4. The [Ca2+]i-length relation defined by the common trajectory shifts appropriately in response to perturbations that have previously been demonstrated to alter the steady-state myofilament Ca2+ sensitivity in skinned cardiac fibres. Specifically, the trajectory shifts leftward in response to an acute increase in pH or following the addition of novel myofilament calcium-sensitizing thiadiazinone derivatives; a rightward shift occurs in response to an acute reduction in pH or following the addition of butanedione monoxime.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593466 TI - Mechanisms of intrinsic tone in ferret vascular smooth muscle. AB - 1. Circular strips from ferret aorta were used to investigate the mechanism of the intrinsic basal tone. 2. Determinations of stiffness using small sinusoidal length changes showed an abolition of both stiffness and force with cooling, but the temperature dependence of the change in active stiffness did not parallel that of force. At temperatures below 22 degrees C there appeared to be a relatively large population of attached, non-force-generating cross-bridges, indicating that separate mechanisms are involved in regulating cross-bridge attachment and the force per cross-bridge. 3. Active intrinsic tone was not affected by removal of extracellular Ca2+ or removal of endothelium. 4. Intracellular ionized Ca2+ concentrations ([Ca2+]i) as measured with the photoprotein aequorin, did not significantly change when intrinsic tone was abolished by cooling. 5. Myosin light chain phosphorylation, as measured by 2 dimensional polyacrylamide gel electrophoresis, significantly decreased on cooling, but the temperature dependence of phosphorylation did not parallel that of force. The change in phosphorylation in the absence of a change in [Ca2+]i suggests the presence of a constitutively active Ca(2+)-independent form of myosin light chain kinase. 6. Maximal concentrations of staurosporine inhibited but did not eliminate intrinsic tone. 7. Changes in myosin light chain kinase and protein kinase C activities may explain part but not all of the intrinsic tone. PMID- 1593467 TI - A capsaicin-sensitive inhibitory reflex from the colon to mesenteric arteries in the guinea-pig. AB - 1. The present in vitro study examined the effect of distension of the distal colon on membrane potential in the inferior mesenteric artery of the guinea-pig. 2. Distension of the distal colon up to an intraluminal pressure of 25 cmH2O induced a hyperpolarization in the inferior mesenteric artery. The average amplitude of hyperpolarizations induced by 2 min distensions of the colon was 3 mV and their average duration was 268 s. 3. Distension-induced hyperpolarizations (DIHs) were abolished in the presence of tetrodotoxin or a low-Ca2+ (0.5 mM) superfusion solution. 4. Superfusion of capsaicin (10 microM) induced slow hyperpolarizing responses in mesenteric arteries. Following application of capsaicin (10 microM), DIHs were abolished. 5. These findings provide strong evidence that mesenteric arteries receive an inhibitory, capsaicin-sensitive sensory innervation from the distal colon which is activated during periods of colon distension to induce hyperpolarization of the arterial smooth muscle. This extramural inhibitory reflex pathway may play a physiological role in co ordinating mesenteric blood flow with changes in gut motility. PMID- 1593468 TI - The stimulus interval-tension relation in enzymatically isolated single myocytes of the frog heart. AB - 1. Apparatus for recording the small tensions developed by electrically stimulated single intact myocytes of frog heart is described. A laser-light optoelectronic transducer was used. The compliance of the force probes was 10-20 nm/nN, with a frequency response of 600-900 Hz in Ringer solution. The myocyte shortening during an ordinary twitch contraction was no greater than 1% of the slack length. The overall sensitivity of the transducer system was 5-10 mV/nN, with a total noise of 0.5-1 nN peak to peak. The experiments were performed at 20 23 degrees C on either atrial or ventricular myocytes at 2.15-2.2 microns sarcomere length, in 1 mM-Ca2+ Ringer solution. 2. Isoprenaline (5 microM), increases in external Ca2+ concentration ([Ca2+]o), and shortening of stimulus interval potentiated the myocyte twitch tension. The dependence of twitch characteristics on these inotropic interventions for all the atrial and ventricular myocytes tested was comparable to that of multicellular preparations under similar experimental conditions. This implies that the enzymatic isolation procedure had not altered the physiological properties of the myocytes. 3. The stimulus interval-tension relation for premature twitches of atrial and ventricular myocytes showed (i) a very steep rising phase in the region of intervals just longer than 0.52 and 0.66 s (the duration of the mechanical refractoriness in atrial or ventricular cells), (ii) a peak, at intervals of 0.7 0.8 s, where the twitch tension was strongly potentiated compared to that of the controls, and (iii) as the stimulus interval was further increased, a progressive return to the control level. The stimulus interval-tension relation for steady state conditions exhibited similar characteristics. 4. The degree of tension potentiation by isoprenaline was greater in the controls than in the earliest test twitches. The result was that the stimulus interval-tension relations for isoprenaline-treated myocytes showed a gentler rise and a lower peak than for untreated cells. 5. The stimulus interval-tension relation of the heart is a basic property of its cells. It is related to changes in the activation level. The higher the activation level reached in control twitches, the lower the stimulus interval-dependent potentiation capability. PMID- 1593469 TI - Cardiovascular responses induced in free-moving rats by immune cytokines. AB - 1. We investigated the effect of intraperitoneal (I.P.) injections of the immune cytokines, interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) on cardiovascular responses in free-moving rats, using a biotelemetry system. 2. The I.P. injection of a small dose of IL-1 beta (1 microgram/kg) induced a monophasic increase in the heart rate, and that of a large dose (10 micrograms/kg) induced biphasic increases in the blood pressure and heart rate. However, the I.P. injection of any of several doses of TNF (1, 10 and 50 micrograms/kg) had no effect on cardiovascular responses in rats. 3. Pre-treatment with I.P. injection of indomethacin (10 mg/kg), an inhibitor of cyclo-oxygenase, significantly suppressed the cardiovascular responses and the increase in the plasma noradrenaline (NA) concentration induced by I.P. injection of IL-1 beta. 4. Microinjection of IL-1 beta (1 and 10 ng) into the preoptic and anterior hypothalamic (PO-AH) region induced dose-dependent increases in the blood pressure and heart rate in rats. These responses were also suppressed by pretreatment with I.P. indomethacin (10 mg/kg). In addition, microinjection of prostaglandin E2 (20 and 100 ng) into the PO-AH region increased blood pressure and heart rate, but that of prostaglandin D2 (100 ng) had no effect. 5. The present results suggest that IL-1 beta stimulates the release of prostaglandins, presumably E series, near regions of the hypothalamus, which act on the hypothalamus to induce activation of the sympathetic nervous system. Subsequently, the blood pressure, heart rate and the plasma level of NA increase. PMID- 1593470 TI - Electrical coupling between cells of the insect Aedes albopictus. AB - 1. Cell pairs of an insect cell line (Aedes albopictus, clone C6/36) were used to study the electrical properties of intercellular junctions. A double voltage clamp approach was adopted to control the voltage gradient between the cells and measure the intracellular current flow. 2. Determinations of junctional conductance (gj) revealed two types of intercellular contacts, gap junctions and cytoplasmic bridges. Identification occurred by means of functional criteria, i.e. the dependency of gj on (i) junctional membrane potential, (ii) non junctional membrane potential, and (iii) heptanol. 3. In cell pairs with putative gap junctions, gj was dependent on the junctional membrane potential (Vj). When determined at the beginning of voltage pulses, gj was insensitive to Vj; when determined at the end of 15 s pulses, it depended on Vj in a bell-shaped manner (70% decrease for a change in Vj of +/- 75 mV). 4. These cell pairs also showed a dependency of gj on the non-junctional membrane potential (Vm). When determined immediately after changing the non-junctional membrane potential in both cells, gj was not affected by Vm; when determined 30 s later, gj was modified by Vm in a S-shaped fashion (100% decrease when Vm was depolarized to +50 mV). 5. Exposure to 3 mM-heptanol gave rise to complete and reversible block of gj in cell pairs with putative gap junctions. 6. Cell pairs susceptible to uncoupling by heptanol revealed junctional currents indicative of the operation of gap junction channels. The single-channel conductance, determined at a Vm of -50 to -70 mV, was 133 pS. 7. In the case of putative cytoplasmic bridges, gj was insensitive to the junctional and non-junctional membrane potential. In addition, it was not affected by 3 mM-heptanol. 8. While most cell pairs showed functional properties characteristic of gap junctions or cytoplasmic bridges, few cell pairs exhibited junctional currents compatible with the co-existence of both junctional structures. PMID- 1593471 TI - Stilbene disulphonates inhibit apparently separate chloride transporters in skeletal muscle of Rana temporaria. AB - 1. Inhibition of 36Cl- efflux in frog muscle by the stilbene disulphonates (SD) SITS (4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulphonate) and DNDS (4,4' dinitro-stilbene-2,2'-disulphonate) depends on the external pH, while the blocking of Cl- conductance with SITS is independent of pH. The 36Cl- efflux inhibition with DNDS has been studied in thin depolarized muscle fibre bundles in order to examine whether this difference is consistent with one transporter or reflects the existence of two mutually independent conductive and non-conductive SD-sensitive Cl- pathways. 2. The 36Cl- efflux response to a sudden inward KCl gradient was studied. At high pH the efflux decreased as predicted for dominant conductive Cl- single-filing, and at low pH the efflux increased in agreement with dominant non-conductive Cl- antiport. DNDS inhibition resulted in the same response, an efflux decrease, at both high and low pH, suggesting a selective reduction of the non-conductive contribution at low pH. 3. The inhibition of 36Cl efflux as a function of the DNDS concentration at an external pH of 6.9 showed complex kinetics, which could be described as the sum of two Michaelis-Menten functions with different half-inhibition concentrations of DNDS. 4. The results support the hypothesis that the stilbene disulphonate-sensitive Cl- transport is mediated by two separate transporters rather than one. PMID- 1593472 TI - Corticospinal projections to upper limb motoneurones in humans. AB - 1. Magnetic stimulation was applied over the motor cortex in forty-five normal human subjects and peristimulus time histograms (PSTHs) of the discharges of single motor units were used to record changes in the firing probability of individual spinal motoneurones of contralateral upper limb muscles. Recordings were obtained from 153 motor units from fourteen upper limb muscles. 2. For the majority of motor units the initial effect was a short latency facilitation. The estimated central conduction velocities and the rise times of the underlying excitatory postsynaptic potentials (EPSPs) were compatible with monosynaptic facilitation by a fast corticospinal pathway. In some motor units the initial effect was a short latency inhibition. Other units showed no statistically significant changes in firing probability. The proportion of the tested motor units in each of these categories depended on the muscle. All of the sampled units of first dorsal interosseous (1DI) showed short latency facilitation, as did the majority of units in the forearm and the biceps brachii. More than half of the sampled motor units of triceps brachii and deltoid showed either no effect or were inhibited. 3. To compare the net short latency actions of the neurones activated by magnetic stimulation on various motoneurone pools, the magnitude of the short latency facilitation or inhibition in a given motor unit was normalized to the magnitude of the short latency facilitation in the 1DI motor unit of the same subject at the same stimulus intensity, and these data were pooled for a number of subjects. 4. 1DI motoneurones received strong net facilitation (estimated mean EPSP amplitude 2.9 +/- 0.2 mV), the motoneurones of forearm muscles and biceps brachii received weaker net facilitation and triceps brachii and deltoid received no net effect. 5. It is concluded that the short latency corticospinal projections to upper limb motoneurones in humans have a distinct pattern which is similar to that in other primates. PMID- 1593473 TI - Marked splenic hyperaemia during post-haemorrhagic hypotension in the rat, rabbit and cat. AB - 1. The regulation of the splenic perfusion during normal and pathological conditions is incompletely understood. We studied the time course of splenic blood flow during the initial (0-24 h) development of haemorrhagic anaemia in awake and anaesthetized rats, as well as in awake rabbits and cats. Another group of rats had either normovolaemic anaemia or beginning polycythaemia. 2. The microsphere method was used to measure splenic blood flow. The awake rats were rendered anaemic either by a heavy (1.5% of body weight) or a moderate (0.7% of body weight) bleeding (hypovolaemia), by haemolysis (normovolaemia) or by bleeding (1.5% of body weight) followed by transfusion of autologous plasma (normovolaemia). Polycythaemia was induced with injections of erythropoietin. The anaesthetized rats as well as the awake rabbits and cats were also bled heavily (1.5% of body weight). 3. In awake rats, splenic blood flow increased to 215% of control within the first 5 min after bleeding. The perfusion declined nearly to baseline over the next 24 h. A similar, but less prominent splenic hyperaemia was detected in the awake rabbits and cats. However, this hyperaemic response was not detected in the normovolaemic, the polycythaemic or the anaesthetized and bled rats. 4. Administration of the adrenergic beta-blocking agent propranolol prior to bleeding significantly attenuated the splenic hyperaemia in the awake rats, while the alpha-blocking agent phentolamine or the cholinergic blocking agent atropine had no effect. 5. Concomitant with the initial increase in splenic perfusion, cardiac output increased to 123% of control in the awake, heavily bled rats. In the bled, anaesthetized rats cardiac output decreased to 91% of control 5 min after bleeding. A decrease in cardiac output to 64 and 70% of control was observed in the awake rabbits and cats, respectively. 6. Immediately following the bleeding, we noticed a substantial release of platelets from the rat spleen. 7. It appears that a heavy acute blood loss in awake rats, rabbits and cats elicits a marked reduction in splenic vascular tone, perhaps mediated by beta adrenergic receptor activity. Anaesthesia abolished this response in rats. Possibly, the induced hypovolaemia triggered an accelerated release of platelets from the rat spleen, dependent on an augmented splenic blood flow. PMID- 1593474 TI - Fluorescence measurements of cytoplasmic and mitochondrial sodium concentration in rat ventricular myocytes. AB - 1. The fluorescent Na+ indicator SBFI was incorporated into isolated ventricular myocytes using the acetoxymethyl (AM) ester. 2. The excitation spectrum was found to be shifted about 20 nm in the cell compared to in vitro. In the cell, an increase of [Na+] decreased fluorescence at 380 nm (F380) and had no effect at 340 nm (F340). The ratio (R = F340/F380) was used as a measure of [Na+]i. 3. In vivo calibration of SBFI for [Na+]i was obtained by equilibrating [Na+] across the plasma membrane with a divalent-free solution in the presence of gramicidin D. 4. Selective removal of the surface membrane with saponin or digitonin released only about 50% of the indicator. Following saponin treatment, cyanide or carbonylcyanide m-chlorphenylhydrazone (CCCP) increased the apparent [Na+] measured by the remaining (presumably mitochondrial) SBFI. It is suggested that mitochondrial [Na+] is normally less than cytoplasmic. 5. Attempts to examine the effects of metabolic inhibition on [Na+]i were hampered by changes of autofluorescence due to changes of [NADH]. It is shown that this effect can be corrected for using the isosbestic signal (excited at 340 nm). 6. Inhibition of both aerobic metabolism (with CN-) and glycolysis (glucose removal or iodoacetate) produced a gradual increase of [Na+]i. This began before the resting contracture developed and may (via Na(+)-Ca2+ exchange) account for some of the rise of diastolic [Ca2+]i seen in previous work. The rise of [Na+]i began at about the same time as the decrease of systolic contraction and therefore at a time when [ATP]i had begun to fall. PMID- 1593475 TI - Metabolic changes with fatigue in different types of single muscle fibres of Xenopus laevis. AB - 1. Peak isometric force of single fast (type 1) and slow (type 3) muscle fibres of Xenopus decreased when fibres were stimulated intermittently above their predicted sustainable duty cycle at 20 degrees C. Type 1 fibres could be fatigued to zero force. In most type 3 fibres force did not decrease below 50% of the original (P0) before activation failure, as indicated by irregular contractions. 2. Fibres were rapidly frozen at different force levels and analysed by high performance liquid chromatography (HPLC) for ATP, IMP, phosphocreatine (PCr) and creatine (Cr). Lactate was determined enzymatically in type 1 fibres only. The relationships between force and PCr, and between force and ATP during fatigue were, apart from the range of values obtained, the same for both fibre types. When force had fallen to about 60-80% of original, PCr was fully reduced. At lower force levels, the ATP content-decreased, and a concomitant rise of IMP content was found. At zero force, ATP had fallen to about 25% of its value in rested type 1 fibres, and up to 200 mumol lactate (g dry weight)-1 had accumulated. 3. Recovery from fatigue was studied in fibres where force had fallen to 0.6 P0 (both fibre types) and 0.2 P0 (type 1 only). After 1 h of recovery ATP had in all cases returned to the level measured in rested fibres. In fibres fatigued to 0.6 P0, force almost returned to its original value. However, in type 1 fibres fatigued to 0.2 P0, it returned to only 0.3 P0. After 1 h of recovery the PCr/Cr ratio in type 1 fibres was lower (probability, P less than 0.05) than in control fibres, whereas in type 3 fibres it was not significantly different from controls. 4. The relationship between peak force and stimulus frequency, which had a sigmoid shape in fully rested fibres, was drastically changed by fatiguing stimulation. Immediately after fatiguing stimulation of type 1 fibres, force hardly increased with stimulus frequency, corresponding to the observation that calcium efflux from the sarcoplasmic reticulum was decreased at high stimulus frequencies. The force-frequency relationship of type 3 fibres was the same before and after intermittent stimulation. PMID- 1593476 TI - Baroreflex control of stroke volume in man: an effect mediated by the vagus. AB - 1. Beat-by-beat changes in cardiac performance in response to arterial baroreceptor stimulation induced by phenylephrine were evaluated by pulsed-wave aortic Doppler ultrasound in eighteen subjects. Stroke distance was used as an index of stroke volume and minute distance as an index of cardiac output; peak velocity was also measured. 2. The sensitivity of the baroreceptor-cardiac reflex was assessed by calculating the slope of the regression lines relating the changes in heart period (R-R interval), peak velocity and stroke distance in response to the rise in systolic blood pressure (SBP) induced by phenylephrine. In ten subjects the experiment was repeated after vagal blockade by atropine. Since the tachycardia induced by vagal blockade could alter the sensitivity of the baroreflex, we compared the results obtained after atropine with those obtained during pacing at similar rates in six subjects with cardiac pacemakers. 3. As R-R interval lengthened in response to the rise in SBP, stroke distance and peak velocity fell sharply. The subjects with a highly sensitive baroreceptor heart rate reflex showed the greatest fall in peak velocity and stroke distance. The slope of the relationship between R-R interval and SBP for each subject correlated closely with that of peak velocity/SBP (correlation coefficient, r = 0.88) and stroke distance/SBP (r = 0.93) relationships. 4. Atropine virtually abolished all the cardiac reflex changes, despite a considerable increase in SBP induced by phenylephrine. At comparable heart rates achieved by pacing the sensitivity of the baroreceptor-cardiac reflex (calculated from the slopes of the regression lines relating changes in stroke distance and in peak velocity to the rise in SBP) was maintained and was significantly greater when compared to that obtained after vagal blockade. 5. These results show that the stimulation of arterial baroreceptors is accompanied by a fall in the Doppler-derived indices of stroke volume and cardiac output. This response is neural and is abolished by atropine, which indicates that it is mediated through the efferent vagus. PMID- 1593477 TI - Central command influences cardiorespiratory response to dynamic exercise in humans with unilateral weakness. AB - 1. Changes in ventilation and cardiovascular variables which occur during exercise may be partly due to 'radiation' of activity in central neurones innervating exercising muscles to the respiratory and cardiovascular control areas. To test this hypothesis, we compared ventilatory and cardiovascular responses to two levels of steady-state exercise with each leg separately, in subjects with painless unilateral leg weakness. We assumed that exercise with a weak leg would require more central neural drive than the same level of exercise with the normal leg. 2. Ventilation during exercise with the weak leg was greater than with the normal leg (P less than 0.02). This was a result of greater tidal volume (Vt; P less than 0.005). There was a greater increase in heart rate (P less than 0.005), and systolic (P = 0.001) and diastolic (P less than 0.02) blood pressures during exercise with the weak leg compared to exercise with the normal leg. The increases in stroke volume and cardiac output during exercise were not different with the two legs. 3. These results support the hypothesis that ventilation, blood pressure and heart rate are influenced by the central neural drive to exercise. PMID- 1593478 TI - Projections of group II-activated midlumbar spinocerebellar tract neurones to the region of nucleus Z in the cat. AB - 1. The possibility that dorsal horn spinocerebellar tract neurones in the midlumbar segments of the cat spinal cord which convey information from hindlimb group II muscle afferents to the cerebellum send collateral projections to medulla in the region of nucleus Z has been examined. 2. Dorsal horn spinocerebellar tract neurones (n = 25) were identified by antidromic activation from the cerebellum and by synaptic activation following stimulation of hindlimb group II afferents. A high proportion (21/25) were also antidromically activated by stimuli delivered to the region of nucleus Z. 3. The results of collision tests between antidromic spikes evoked from the cerebellum and the medulla and the fact that the latency for antidromic activation from nucleus Z at threshold was greater than from the cerebellum indicates that at least 11/25 (44%) of the neurones had collateral projections to the medulla. 4. Antidromic threshold mapping revealed that some of the neurones could be activated from parts of the dorsal medulla adjacent to, but not directly overlying, nucleus Z. The possible relevance of these data with regard to sensation of lower limb position and motion is discussed. PMID- 1593479 TI - Liquid flow across the epithelium of the artificially perfused lung of fetal and postnatal sheep. AB - 1. The lungs of five fetal (133-140 days gestation) and thirty-four postnatal (2 240 days) sheep were artificially perfused in situ with warmed and oxygenated sheep blood. In postnatal animals the airspace of the lung was filled with liquid similar in composition to fetal lung liquid. In fetal and postnatal animals luminal liquid volume was measured by the impermeant tracer technique. 2. Under resting conditions the pulmonary epithelium of fetal animals secreted liquid at a mean (+/- S.E.M.) rate of 2.0 (+/- 0.4) ml (kg body weight)-1 h-1, those of postnantal animals absorbed liquid at -1.8 (+/- 0.2) ml (kg body weight)-1 h-1. 3. Addition of 2,4-dinitrophenol to achieve a concentration of 1.5 x 10(-3) M in the perfusing blood in postnatal animals caused complete cessation of liquid absorption. 4. Light and electron microscopic examination of the lung after periods of up to 6 h of artificial perfusion showed no evidence of epithelial damage. From 3 h onwards, liquid accumulation was evident in the perivascular spaces. 5. Addition of adrenaline to the perfusate in fetal animals caused absorption of liquid to occur at a mean rate of -2.9 (+/- 1.3) ml (kg body weight)-1 h-1. In postnatal animals adrenaline caused the rate of liquid absorption to increase from a mean rate of -1.4 (+/- 0.2) to -2.2 (+/- 0.3) ml (kg body weight)-1 h-1. 6. In the fetus addition of amiloride (0.8 x 10(-4) M) to the luminal fluid blocked adrenaline-induced liquid absorption and caused secretion to occur at 1.3 (+/- 0.3) ml (kg body weight)-1 h-1. 7. In postnatal animals the response to amiloride was age dependent. In newborn lambs (2-14 days) amiloride blocked liquid absorption and caused secretion of liquid to occur in seven out of eight animals at a mean rate of 0.9 (+/- 0.3) ml (kg body weight)-1 h-1 (n = 8). In older animals (15-240 days) the characteristic response to amiloride was slowing of the rate of liquid absorption (mean rate of absorption, 0.2 (+/- 0.09) ml (kg body weight)-1 h-1, n = 18) with liquid secretion being seen in only three of eighteen animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593481 TI - Respiratory muscle recruitment during selective central and peripheral chemoreceptor stimulation in awake dogs. AB - 1. In four awake dogs we measured EMG activity of three inspiratory and four expiratory muscles during sustained central chemoreceptor stimulation (CO2 inhalation), and peripheral chemoreceptor stimulation (intravenous infusion of almitrine bismesylate (almitrine)). By using this selective pharmacological stimulation of the peripheral chemoreceptors and reversibly cold-blocking pulmonary stretch receptors, we were able to determine the effects of each type of stimulation on respiratory muscle recruitment in the absence of such complicating influences as pulmonary stretch receptor feedback, cerebral hypoxia or hypocapnia, and differences in breathing pattern. 2. During 10 min of steady state hyperpnoea (minute ventilation VI, approximately twice eupnoea) caused by either hypercapnia or isocapnic stimulation of the carotid bodies with almitrine, all three inspiratory and all four expiratory muscles demonstrated significant and sustained elevations in EMG activity. 3. With both types of chemoreceptor stimulation, as tidal volume, VT, increased, so did the mean electrical activities of the crural diaphragm (r = 0.88), costal diaphragm (r = 0.93), parasternals (r = 0.82), triangularis sterni (r = 0.74), transversus abdominis (r = 0.77), external obliques (r = 0.68) and internal intercostals (r = 0.75). 4. In each dog, the response of ventilation and of the diaphragmatic EMG to a given level of central or peripheral chemoreceptor stimulation is highly reproducible from one test day to the next. On the other hand, accessory inspiratory and expiratory abdominal and rib cage muscles in two of the four dogs showed highly significant changes from day to day in the amount of their EMG activity at any given VT. 5. During steady-state ventilatory stimulation, 2 min intervals were chosen during which the two types of chemoreceptor stimulation had caused hyperpnoeas with similar values for VT, total time per breath (TTOT) and inspiratory time divided by the total time (TI/TTOT). Comparison of EMG activities during these matched hyperpnoeas revealed that there were no differences in the activities of any of the muscles between the two forms of stimulation. We conclude that peripheral chemoreceptor stimulation causes significant and sustained recruitment of expiratory muscles even in the absence of pulmonary feedback and that both expiratory and inspiratory muscles are recruited to the same extent during peripheral chemoreceptor stimulation as they are during an identical hyperpnoea caused by central chemoreceptor stimulation. PMID- 1593480 TI - Role of ATP-sensitive K+ channels during anoxia: major differences between rat (newborn and adult) and turtle neurons. AB - 1. It is well known that anoxia induces an increase in extracellular K+. The underlying mechanisms for the increase, however, are not well understood. In the present study, we performed electrophysiological, pharmacological and receptor autoradiographic experiments in an attempt to examine K+ ionic homeostasis during anoxia. Ion-selective microelectrodes were employed to measure intracellular and extracellular K+ activity from hypoglossal neurons in brain slices. 2. During 3-4 min anoxia, adult hypoglossal neurons lose a large amount of their intracellular K+ and this contributes in a major way to the 8-fold increase in extracellular K+. 3. Loss of intracellular K+ from hypoglossal neurons is, to a great extent, due to activation of certain specific K+ channels. Glibenclamide, a potential sulphonylurea ligand and a specific blocker of ATP-sensitive K+ (KATP) channels, has no effect on K+ homeostasis during oxygenated states, but almost halves the anoxia-induced increase in extracellular K+ in the adult rat. 4. [3H]glibenclamide autoradiography shows that the hypoglossal nucleus in the adult rat has high sulphonylurea receptor density, a finding that is consistent with our electrophysiological observation. 5. Since we have previously shown that newborn mammals and reptiles are more resistant to O2 deprivation than adult mammals, we performed comparative studies among adult rat, newborn rat and adult turtle. In sharp contrast to the adult rat, extracellular K+ activity in newborn rat and adult turtle brain increases little (10 to 100 times less than the adult rat) and glibenclamide has a small and insignificant effect on K+ efflux in the newborn rat and none in the turtle. Glibenclamide receptor binding sites are much lower in the newborn rat than in the adult rat central nervous system (CNS) and barely detectable in the turtle brain. 6. These results support the hypothesis that in the adult rat, K+ is lost during anoxia from neurons through sulphonylurea receptor or KATP channels in a major way. Generally, however, KATP channels are poorly expressed in the newborn rat and adult turtle CNS and have little role to play during O2 deprivation. PMID- 1593482 TI - Inactivation of the slow calcium current in twitch skeletal muscle fibres of the frog. AB - 1. We investigated inactivation of the slow calcium current (ICa) at very positive potentials (over 30-40 mV) and recovery from inactivation in cut twitch skeletal muscle fibres of the frog, using the double-vaseline-gap technique. External solutions were buffered against changes in [Ca2+] (Ca(2+)-buffered) with malate. Internal solutions were Ca(2+)-buffered with high concentrations of either EGTA (60 mM) or BAPTA (30 mM). 2. ICa decayed to a steady-state level somewhat less than zero. Inactivation was most rapid at a potential 10 mV more negative than that which elicited the maximal ICa. 3. Involvement of current dependent processes (i.e. tubular Ca2+ depletion and Ca2+ entry-dependent inactivation) in determining the decay of ICa was excluded, since inactivation was not affected by replacing Ca2+ with Ba2+ or when the size of ICa was reduced by decreasing the [Ca2+]o. Partial block of Ca2+ channels with nifedipine slowed inactivation. This was, however, independent of the size of ICa. Furthermore, neither the peak of ICa nor its time constant of decay nor the time course of ICa recovery from inactivation were affected by changing the [Ca2+]i from pCa 10 to 6. 4. ICa was potentiated during a post-pulse preceded by a pre-pulse at potentials ranging from -60 to -30 mV, whereas a U-shaped inactivation curve was observed at pre-pulse potentials more positive than -30 mV. This curve was asymmetric, since the ascending branch stabilized at a level less than unity. The U-shaped form of the curve depended on post-pulse voltage: it became more pronounced when the post-pulse depolarization increased. Moreover, the activation and inactivation kinetics of ICa during the post-pulse differed from control values. Similar results were found when Ca2+ was replaced with Ba2+. 5. The ICa recovery from inactivation was voltage dependent from -50 to -80 mV; it was voltage independent at more negative potentials, proving that recovery includes a voltage-independent step. 6. The asymmetric U-shaped inactivation curve can be reproduced by a four-state cyclic model without assuming a Ca(2+)-dependent step. Taking into account that recovery from inactivation includes a voltage independent step which becomes rate limiting at extreme negative potentials, and that during the post-pulse the activation kinetics is faster, we propose a model which has six states, two closed, one open and three inactivated. PMID- 1593483 TI - Factors causing difference in force output among motor units in the rat medial gastrocnemius muscle. AB - 1. The isometric contractile properties and morphological characteristics of the muscle unit portion of motor units were investigated in the medial gastrocnemius (MG) muscle of Fischer 344 rats. Individual motor units were functionally isolated by stimulating single MG axons in finely dissected ventral root filaments. 2. To study the mechanical properties of the motor units in the rat MG muscle, ninety-six motor units in five animals were classified into three categories (type FF, FR and S units) using two physiological criteria: presence or absence of the 'sag' property and fatigability. The relative distribution of the different motor unit types in the sample was 35.4% for type FF, 47.9% for type FR, and 16.7% for type S units. 3. There was little overlap in the distribution of twitch contraction time between type F (including types FF and FR) and type S units. The mean value was 17.1 ms for type FF, 15.7 ms for type FR, and 28.0 ms for type S units. Type FF units produced the largest tetanic tension (mean +/- S.D.; 201 +/- 75 mN). Tension output of type S units was the smallest (15 +/- 6 mN), and that of type FR units was intermediate (100 +/- 45 mN). These values were significantly different. 4. A muscle unit portion of twenty-three motor units (8 FF, 6 FR, and 9 S units) was depleted of its glycogen through repetitive stimulation after characterization of its mechanical properties. Cross-sectional areas of units fibres and innervation ratio were directly measured in sections stained for glycogen using a periodic and acid Schiff (PAS) reaction. Specific tension of unit fibres was calculated by dividing the maximum tetanic tension of a unit by its total fibre area. 5. The number of unit fibres ranged from 44 to 77 for type S, 116 to 198 for type FR, and 221 to 356 for type FF units, and differences among their means (66, 154 and 271, respectively) were significant. Tetanic tension was correlated with innervation ratio for all of the twenty-three units, or units within a particular type. 6. Mean fibre area for type S units (1983 microns2) was significantly smaller than that for type FF units (3489 microns2). Fibres belonging to type FR units had an intermediate size (2648 microns2). Correlation between tetanic tension and fibre area was significant for either all units or units within a particular type. 7. Total cross-sectional area was significantly different among the motor unit types, and was highly correlated to the maximum tetanic tension.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593484 TI - Cl- and Na+ homeostasis during anoxia in rat hypoglossal neurons: intracellular and extracellular in vitro studies. AB - 1. To understand the mechanisms which lead to acute neuronal swelling during anoxia, we studied the ionic movements of Cl- and Na+ during O2 deprivation in the hypoglossal (XII) neurons of rat brain slices using double-barrelled ion selective microelectrodes. 2. Baseline extracellular Cl- and Na+ activities ([Cl ]o, [Na+]o) were 128.3 +/- 7.4 and 150.0 +/- 3.4 mM respectively (n = 12) in the adult. Similar baseline values were obtained from neonatal brain slices. 3. During a period of anoxia (4 min), [Na+]o decreased by about 40 mM in adult slices while [Na+]o did not show any significant change in the neonate (n = 12). Although anoxia induced a significant decrease of [Cl-]o in both adult and neonate, [Cl-]o dropped 7 times more in the adult than in the neonate (n = 12). 4. Intracellular Cl- activity ([Cl-]i) was studied in twenty-seven adult hypoglossal cells. All showed an increase in [Cl-]i) was studied in twenty-seven adult hypoglossal cells. All showed an increase in [Cl-]i with O2 deprivation. Detailed analysis carried out on ten hypoglossal neurons showed a baseline [Cl-]i of 11.4 +/- 4.5 mM and an increase in [Cl-]i by 20.6 +/- 7.2 mM during O2 limitation. 5. Baseline [Cl-]i in neonatal XII neurons was similar to that of the adult. Anoxia, however, produced an increase in [Cl-]i by only 4.5 +/- 2.4 mM (n = 7). This increase in [Cl-]i was significantly less than that in the adult (P less than 0.001). Prolonged anoxia (6-12 min) in the neonate led to a more substantial increase in [Cl-]i, an observation consistent with the decrease in [Cl-]o after prolonged O2 deprivation. 7. We conclude that during anoxia: (1) intracellular [Cl-] increases in the adult and this most likely occurs because of entry of extracellular Cl- into the cytosol and (2) there is a major maturational difference in mechanisms regulating Cl- and Na+ homeostasis between newborn and adult brain tissue. We speculate that these mechanisms may account, at least partially, for the relative tolerance to anoxia in the newly born. PMID- 1593485 TI - Role of an inwardly rectifying potassium current in rabbit ventricular action potential. AB - 1. Whole-cell voltage-clamp measurements were made of the time- and voltage dependent properties of the inwardly rectifying background potassium current IK1, in single myocytes from rabbit ventricle. The main goal of these experiments was to define the role of IK1 in the plateau and repolarization phases of the action potential (AP). 2. Action potentials from single ventricular myocytes were used as the command signals for voltage-clamp measurements. In these 'action potential voltage-clamp' experiments, IK1 was isolated from other membrane currents by taking the difference between control currents and currents in K(+)-free bathing solution. The results show that IK1 is small during the plateau, but then rapidly increases during repolarization and declines in early diastole. 3. Evidence of an important functional role for IK1 in AP repolarization was obtained by comparing the magnitude of IK1 and the rate of change of membrane potential (dVm/dt) in the same cell during the AP. The time courses of IK1 and dVm/dt during the AP were closely correlated, indicating that IK1 was the principal current responsible for final repolarization. 4. Rectangular voltage-clamp steps were used to study time- and voltage-dependent changes in IK1 at membrane potentials corresponding to the repolarization phase of the AP. 'Slow' relaxations or tail currents, lasting 100 300 ms, were consistently recorded when the cell was repolarized to potentials in the range -30 to -70 mV, following depolarizations between +10 and -10 mV. 5. The close correlation between the magnitude of the steady-state IK1 (in an external K+ concentration of 5.4 mM), which was outward for membrane potentials in the range -30 to -70 mV, and the magnitude of the tail currents, suggests that they resulted from a slow increase, or reactivation, of IK1. 6. The component of the slow tails due to reactivation of IK1 can be separated from a previously described component due to Na(+)-Ca2+ exchange since the IK1 component: (i) does not depend on the presence of the calcium current, ICa; (ii) can be recorded when internal EGTA (5 mM) suppresses large changes in [Ca2+]i; (iii) does not depend on the Na+ electrochemical gradient; (iv) is abolished in K(+)-free external solution; and (v) is not present in rabbit atrial myocytes, in which IK1 is very small. 7. The time- and voltage-dependent properties of IK1 revealed by these tail current experiments suggest that the measured magnitude of IK1 will be dependent on the voltage-clamp protocol.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593486 TI - Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes. AB - 1. Endothelin is a vasoactive peptide released from vascular endothelial cells which has potent cardiac inotropic effects. We examined the effect of endothelin on the verapamil-sensitive Ca2+ current (ICa) in enzymatically dispersed rabbit ventricular myocytes. 2. Using the whole-cell voltage clamp technique with a standard dialysing pipette solution, the application of extracellular endothelin (20 nM) did not increase the peak ICa, but in fact caused a small reversible decline (903 +/- 109 pA without endothelin, 727 +/- 95 pA with endothelin (means +/- S.E.M., n = 14, P less than 0.05)). 3. If GTP (100 microM) was added to the pipette solution, the extracellular application of endothelin (0.2 or 20 nM) caused a large, reproducible increase in peak ICa (871 +/- 85 pA without endothelin, 1230 +/- 110 pA with 20 nM-endothelin (n = 10, P less than 0.05). The endothelin enhancement of ICa occurred after a delay of approximately 3-4 min at room temperature. 4. The GTP requirement for the endothelin effect on ICa suggests that its effect may be mediated through a G protein-dependent pathway. To investigate this further, experiments were performed with pipette solutions containing guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), a GDP analogue which inhibits G protein cycling. With the addition of GDP beta S (0.5-5.0 mM) to the pipette solution (along with 100 microM-GTP), the effect of endothelin on peak ICa was blocked (1062 +/- 86 pA without endothelin, 1170 +/- 134 pA with endothelin (n = 11, P greater than 0.05)). 5. Incubation of myocytes with pertussis toxin (500 ng/ml) prevented the partial ACh-induced reversal of the isoprenolol enhancement of ICa. However, this identical treatment failed to block the endothelin enhancement of the voltage-dependent Ca2+ current (n = 4). 6. Taken together, these results confirm that while the effect of endothelin in rabbit cardiac ventricular myocytes is mediated through a G protein-dependent pathway, the G protein involved is pertussis toxin-insensitive. PMID- 1593487 TI - Ionic currents of outer hair cells isolated from the guinea-pig cochlea. AB - 1. Whole-cell currents were measured in outer hair cells isolated from each turn of the organ of Corti of the guinea-pig. 2. The slope input conductances at -70 mV of the cells ranged from 3.6 to 51 nS depending on the length of the cell. Shorter cells from the basal turns of the cochlea had the highest values. The membrane time constant of the cells varied from 3 to 0.2 ms from the apex to the base. 3. Irrespective of the position of the cells along the cochlea, three distinct currents were found. Each type of current was found in approximately the same proportion in all cells. 4. An outward K+ current was present which activated at potentials more positive than -35 mV. The current was sensitive to tetraethylammonium (30 mM), quinidine (100 microM) and nifedipine (50 microM). It could be removed by replacing external Ca2+ with Ba2+ or Mg2+. The current was also removed by substituting Nai+ or Csi+ for Ki+ pipette solution. This outwardly rectifying current appears similar to the calcium-activated K+ current described in other hair cells. 5. The main current present at membrane potentials from -90 mV to -50 mV was a second voltage-activated K+ current. It was 50% activated at -80 mV, and relaxed with a time constant of 20-40 ms on hyperpolarization to -120 mV. Near rest the kinetics were essentially time dependent , but depended upon the external K+ concentration. The current was blocked by 5 mM external Cs+. 6. This current was highly selective for K+. Measured from reversal of the tail currents, the permeability ratio PK:PNa was approximately 30:1. Depolarization of the cell, presumed to lead to an elevation of intracellular calcium, produced a prolonged activation of the current. 7. A third current found in the cells was a cation current. By external ion replacement, the selectivity sequence was determined to be Ca2+ greater than Na+ approximately equal to K+ greater than choline+ greater than NMDG+ (respective permeabilities relative to Na: 2.9, 1.0, 0.99, 0.63 and 0.37). This current was reduced by external Ba2+ (3 mM) and by nifedipine (50 microM). The activation of this current appeared to depend upon raised levels of Cai2+. 8. These currents account for reported in vivo properties of cochlear outer hair cells as cells permeable to potassium at large negative resting potentials. The consequences for sound detection in the cochlea are briefly discussed. PMID- 1593488 TI - Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. AB - 1. Capsaicin, the potent algesic substance in chilli peppers, was applied topically to, or injected intradermally into or outside, the receptive fields of 14 C mechanoheat (polymodal) nociceptor units in awake humans. The nociceptor discharges were recorded using microelectrodes inserted into the peroneal nerve. Simultaneously, the subjects estimated the magnitude of pain as a function of time during the first 1.5-3 min after injection. Magnitude estimates of pain produced by heat and/or mechanical stimuli were also obtained before and after capsaicin in order to assess the magnitude of cutaneous hyperalgesia. 2. An injection within or adjacent to, but not greater than 4 mm outside, the receptive fields of C nociceptor units evoked discharges. The magnitude of pain and the mean discharge rate of the units were both maximal on injection, declining rapidly over the next 1-3 min, which indicates that these nociceptors contribute to the magnitude and duration of pain evoked by capsaicin injection. 3. Reduced or abolished excitability in C nociceptors after capsaicin injection within the receptive fields correlated with analgesia at the injection site. 4. Capsaicin injection produced a wide surround area of mechanical hyperalgesia, i.e. pain on gently stroking the skin or abnormally intense pain on punctate stimulation. Nevertheless, the injections did not lower the thresholds or enhance the responses to such mechanical stimuli of C nociceptor units with their receptive fields in this hyperalgesic area. 5. Topical application of capsaicin evoked on going discharges in four units tested. Both nociceptor response thresholds and pain thresholds were lowered for heat from 45 to 35 degrees C. A newly developed weak response to stroking the skin in two units after capsaicin was accompanied by faint pain. 6. On-going activity in sensitized C nociceptors and concomitant pain were effectively reduced by cooling the skin in the receptive area. 7. It is concluded that activity in C mechanoheat (polymodal) nociceptors contributes to the magnitude and duration of pain evoked by intradermal injection of capsaicin. The after-effects of capsaicin on C nociceptor excitability depend on concentration: high concentration (by injection) leads to desensitization, whereas low concentration (by topical application) leads to sensitization. On going discharges and lowered response thresholds to heat in these units after topical application of capsaicin correlates with background pain as well as lowered pain thresholds to heat of the affected skin (primary hyperalgesia). The unchanged responsiveness of C nociceptors in the skin well outside the injection area indicates that central rather than peripheral sensitization accounts for the observed mechanical hyperalgesia in this region (secondary hyperalgesia). PMID- 1593490 TI - Increased production of tumour necrosis factor by peripheral blood leukocytes in patients with recurrent oral aphthous ulceration. AB - Much evidence suggests that recurrent oral aphthous ulceration (RAU) is an immunologically mediated disease. Tumour necrosis factor has multiple biologic properties, some of which may be relevant to the pathogenesis of RAU. This study has assessed its production by peripheral blood leukocytes from aphthous patients in active and remission phases of disease and from patients with nonaphthous ulceration (diseased controls). Each ulcer patient was studied in parallel with a matched healthy control volunteer. A bioassay against the standard mouse fibrosarcoma line, L929, was used to assess the levels of tumour necrosis factor alpha (TNF). Significantly greater amounts of TNF were released from unstimulated monocyte-enriched and monocyte-depleted leukocyte fractions in active RAU compared with those from healthy control donors, suggesting that this cytokine may be associated with RAU. PMID- 1593489 TI - Central changes in processing of mechanoreceptive input in capsaicin-induced secondary hyperalgesia in humans. AB - 1. Capsaicin, the algesic substance in chilli peppers, was injected intradermally in healthy human subjects. A dose of 100 micrograms given in a volume of 10 microliters caused intense pain lasting for a few minutes after injection and resulted in a narrow area of hyperalgesia to heat and a wide surrounding area of hyperalgesia to mechanical stimuli (stroking) lasting for 1-2 h. 2. Nerve compression experiments with selective block of impulse conduction in myelinated (A) but not in unmyelinated (C) fibres indicated that afferent signals in C fibres contributed to pain from capsaicin injection and to heat hyperalgesia, whereas conduction in afferent A fibres was necessary for the perception of mechanical hyperalgesia. 3. Electrical intraneural microstimulation normally eliciting non-painful tactile sensations was accompanied by pain when the sensation was projected to skin areas within the region of mechanical hyperalgesia induced by capsaicin injection. 4. The threshold for pain evoked by intraneural microstimulation was reversibly lowered and pain from suprathreshold stimulation was exaggerated during the period of mechanical hyperalgesia, regardless of lidocaine anaesthesia of the cutaneous innervation territory of the stimulated fibres. 5. The results indicate that hyperalgesia to stroking on a skin area surrounding a painful intradermal injection of capsaicin is due to reversible changes in the central processing of mechanoreceptive input from myelinated fibres which normally evoke non-painful tactile sensations. PMID- 1593491 TI - Immunoglobulin G subclasses in recurrent aphthous stomatitis. AB - Serum levels of immunoglobulin G (IgG) subclasses were examined in 71 adult patients with minor recurrent aphthous stomatitis (MiRAS). Seven patients (10%) had altered IgG subclasses: six had marginally raised IgG1 levels and one had a low level of IgG3. It is concluded that abnormalities of IgG subclass levels do not underlie MiRAS. PMID- 1593492 TI - Quantitative evaluation of Langerhans cells in median rhomboid glossitis. AB - Langerhans cells (LC) serve as antigen presenting cells and provide immune surveillance within epithelia. Since depression of LC number and/or function may allow tolerance to antigens, we evaluated LC in median rhomboid glossitis (MRG), a condition linked to persistent candidal infection of lingual mucosa. Material included a total of 36 cases of MRG (7 of which did not show PAS + fungi) and 6 controls. LC were identified by their expression of S-100 and HLA-DR antigens and quantified using image analysis. Equal numbers of LC were identified using S-100 + and HLA-DR + markers. The density of LC (cells/mm of basement membrane, mean +/ SD) in both PAS + MRG (2.6 +/- 1.3) and PAS-MRG (3.0 +/- 1.7) was markedly depressed compared with controls (17.2 +/- 6.4), (P less than 0.001). These findings indicate that the LC network is perturbed in MRG, and are consistent with the view that of localized defect in immune surveillance may contribute to persistent fungal infection of the oral mucosa. PMID- 1593493 TI - Alterations in taste acuity associated with allogeneic bone marrow transplantation. AB - Taste detection and recognition thresholds were monitored in 10 patients for up to 1 yr after allogeneic bone marrow transplantation (BMT). As well as a control group of 12 healthy volunteers, taste acuity was tested in 10 patients, who had undergone BMT 2-5 yr previously. Immediately after transplantation, there was significant hypogeusia of all four taste modalities compared to registrations one week before the aplastic phase and also compared to the healthy control group. Although some normalization of taste thresholds was registered 3-6 months after transplantation, most subjects still experienced dysgeusia. Of the four taste modalities, the most frequently recorded change was a raised threshold for salt. In about 80% of the patients taste acuity had recovered to the control values one year after transplantation. The group tested 2-5 yr after BMT had normal values for taste acuity. PMID- 1593494 TI - Odontogenic lesions in opercula of permanent molars delayed in eruption. AB - Opercula of permanent first and second molars delayed in eruption were investigated histologically to detect possible causes of eruption failure. The material comprised operation specimens from exposure of 74 non-erupted molars in 63 young individuals (34 boys, 29 girls). Eighteen of the 74 specimens (or 24.3%) were diagnosed as "classical" odontogenic tumors belonging to the following entities: ameloblastic fibroma (seven), ameloblastic fibrodentinoma (six), ameloblastic fibro-odontoma (four) and complex odontoma (one). Twenty-two specimens (or 29.7%) showed a hitherto unrecognized odontogenic lesion of hamartomatous character, termed odontogenic giant cell fibromatosis (OGCF). Thus, 54.1% of the specimens could be diagnosed as odontogenic tumors or hamartomas. Histomorphologic changes could not be detected in the remaining 34 specimens (45.9%). Odontogenic tumors were associated with unerupted first molars much more frequently than with second molars (ratio 8:1). The OGCF had a strong association with unerupted mandibular molars. Further, opercula of mandibular first molars frequently revealed odontogenic lesions whereas tissue overlying the crown of unerupted maxillary second molars often was reported as normal operculum. PMID- 1593496 TI - Ameloblastoma with dentinoid induction: dentinoameloblastoma. AB - Ameloblastomas do not generally show evidence of induction, however rare cases associated with an odontome have been reported, and are referred to as odontoameloblastoma. In this paper the first known case of an ameloblastoma showing evidence of induction of dentinoid by tumor cells but without concomitant formation of enamel is recorded. The lesion occurred in the angle and ramus of the mandible of a 24-yr-old Asian man and was largely unicystic. In one area however, solid tumor was present which consisted both of infiltrating follicles of typical ameloblastoma tissue and solid sheets of ovoid to spindle cells containing abundant amounts of a homogenous eosinophilic extracellular material, interpreted as dentinoid, and psammamomatous type dystrophic calcifications. Electron microscopic examination of formalin-fixed tissue showed this dentinoid material to consist of interlacing collagen fibrils embedded in a structureless ground substance. At the periphery of the dentinoid globules the collagen fibres were arranged in parallel layers. A final diagnosis of dentinoameloblastoma was made. PMID- 1593495 TI - Odontogenic cysts of the anterior mandible of sheep. AB - Cysts of this site are quite common in mature ewes in New Zealand and the British Isles, although their true prevalence is not yet known. In most examples, an unerupted incisor is embedded in their wall but some do not contain a tooth. The cysts are lined by parakeratinized stratified squamous epithelium and generally exhibit a flat interface between the epithelium and the connective tissue. They may become secondarily infected, in which case they exhibit chronic inflammation. In some cases, foci of cementum are attached to the epithelial lining. When a tooth is involved, the cysts arise from various locations along its crown, which in sheep is normally covered by a thin layer of cementum. Some of these unerupted teeth exhibit irregular hypercementosis and/or external resorption which is repaired by cementum. In some examples there is a fistula between the cyst and the oral cavity, either through a deep periodontal pocket or from the incisal edge of the unerupted tooth piercing the overlying mucosa. PMID- 1593497 TI - Orientation of Aplysia californica to distant food sources. AB - The behavior of the marine mollusc Aplysia was examined under different experimental conditions designed to determine the food searching strategy of the animals. In a small, open field tank with still water, the animals took an average of 42 min to find a piece of seaweed, even though the stimulus was never located more than 30 cm away from the animal. Observations of the animals indicated that their search was not directed, without a clear tendency towards the food, and during the course of a search, they often crawled through most of the area of the tank. The search time, the distance travelled, and the strategy of the search of the animals was similar for different types of seaweed. If animals were aroused into activity by the presence of seaweed extract, the time for them to contact a piece of odorless glass fiber paper in the open field was not significantly different than that for a piece of seaweed. The probability at which the animals contacted the seaweed, as a function of the distance travelled, resembled the detection probability determined according to a theory of random search. We thus propose that the aroused animals move in a random pattern until they are very close to the food. This strategy can be advantageous in still water since chemicals do not provide distinct gradients that can serve as cues for chemotactic orientation from distances greater than a few centimeters from the source. In a Y-maze in still water, Aplysia did not perform above chance in selecting the arm that contained the seaweed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593498 TI - Local spiking interneurons controlling the equilibrium response in the crayfish Procambarus clarkii. AB - 1. In the crayfish brain, the responses of local spiking interneurons to body roll simulated by bending of statocyst hairs, were investigated with intracellular recording and staining techniques. The neurons had two separate branching portions in the protocerebrum and the deutocerebrum. They were named as type-I local neurons and further classified into 5 types (ac-U, vplc-U, vplc-B, vupc-U, vupc-B). 2. Vupc-U neurons showed excitatory responses and vplc-U neurons showed inhibitory responses to inward hair deflection of the statocyst ipsilateral to their deutocerebral branches. The other 3 types were of mixed populations of the interneurons showing either excitatory or inhibitory responses to the stimulation. 3. Of 10 type-I local neurons showing excitatory responses to inward hair deflection, 6 interneurons had output effects on oculomotor and/or descending neurons. All these 6 interneurons showed large EPSPs and much higher frequency of spikes to the hair stimulation than those of the other 4. All 8 type I local neurons that showed inhibitory responses had no output effects. 4. Type-I local neurons controlled two equilibrium responses, compensatory eye movement and righting reflex, either simultaneously or independently. PMID- 1593499 TI - Jaw movement kinematics and jaw muscle (EMG) activity during drinking in the pigeon (Columba livia). AB - Movements of the maxilla and mandible were recorded during drinking in the head fixed pigeon and correlated with electromyographic activity in representative jaw muscle groups. During drinking, each jaw exhibits opening and closing movements along both the dorso-ventral and rostro-caudal axes which may be linked with or independent of each other. All subjects showed small but systematic increases in cycle duration over the course of individual drinking bouts. Cyclic jaw movements during drinking were correlated with nearly synchronous activity in the protractor (levator) of the upper jaw and in several jaw closer muscles, as well as with alternating activity in tongue protractor and retractor muscles. No EMG activity was ever recorded in the lower jaw opener muscle, suggesting that lower jaw opening in this preparation is produced, indirectly, by the contraction of other muscles. The results clarify the contribution of the individual jaws to the generation of gape variations during drinking in this species. PMID- 1593500 TI - The latency of the response of Limulus photoreceptors to inositol trisphosphate lacks the calcium-sensitivity of that to light. AB - The latent period before depolarization of Limulus ventral photoreceptors by light flashes was compared with that following brief, intracellular, pressure injection of d-myo-inositol 1,4,5 trisphosphate. At temperatures between 18 degrees C and 22 degrees C and with an extracellular calcium concentration of 10 mM, the responses of 4 cells to light and to injections of 100 microM inositol trisphosphate displayed average latencies of 71 and 56 ms, respectively. The latencies of responses to InsP3 included an estimated 20 ms dead-time inherent in the injection method. Reducing the temperature lengthened the latency of the response to light (Q10 approximately 3.2 between 7 and 22 degrees C) more than that to inositol trisphosphate (Q10 approximately 2.3). Bathing the photoreceptors in seawater containing no added calcium and 1 mM of the calcium chelator EGTA greatly increased the latency of the light response at all temperatures, but did not increase the latency of the response to inositol trisphosphate. We conclude that the response to inositol trisphosphate lacks the calcium- and temperature-sensitive latent period which characterizes the response to light. If inositol trisphosphate acts, via the release of stored calcium, to stimulate an intermediate in the visual cascade, then that intermediate would appear to be downstream from the latency-generating mechanism. PMID- 1593501 TI - Configurational pattern discrimination responsible for dishabituation in common toads Bufo bufo (L.): behavioral tests of the predictions of a neural model. AB - Recently, a neural model of visual pattern discrimination for stimulus-specific habituation was developed, based on previous behavioral studies which demonstrated that toads exhibit a dishabituation hierarchy for different worm like stimuli. The model suggests that visual objects are represented by temporal coding and predicts that the dishabituation hierarchy changes when the stimulus/background contrast direction is reversed or the stimulus size is varied. The behavioral experiments reported in this paper were designed to test these predictions. (1) For a pair of stimuli from the contrast reversal prediction, the experimental results validated the theory. (2) For a pair of stimuli from the size reduction prediction, the experimental results failed to validate the theory. Further experiments concerning size effects suggest that configural visual pattern discrimination in toads exhibits size invariance. (3) Inspired by the Groves-Thompson account of habituation, we found that dishabituation by a second stimulus has a separate process from habituation to a first stimulus. This paper serves as an example of a fruitful dialogue between experimentation and modeling, crucial for understanding brain functions. PMID- 1593502 TI - Stimulus-evoked slow potential shifts and changes in [K+]0 of the frog optic tectum. AB - In 17 frogs (Rana esculenta var ridibunda) immobilised with succinyl choline the optic tectal surface was stimulated by trains of electrical pulses or by a flash to the contralateral eye. Sustained potential shifts (SPSs) and changes in extracellular potassium concentration (delta[K+]0) were simultaneously recorded. In response to electrical stimulation SPSs of maximal amplitudes (1.19 +/- 0.1 mV) were recorded between 50 and 200 microns in depth and maximal delta[K+]0 (0.69 +/- 0.08 mM) between 100 and 350 microns. The changes of SPS and delta[K+]0 showed a close similarity in experiments with changes in voltage, pulse duration and frequency of stimuli within a train. The induced SPS had a duration of 28 +/- 1.54 s, the delta[K+]0 of 32 +/- 1.23 s. The flash stimulus induced an SPS and delta[K+]0 of maximal amplitudes between 50 and 200 microns in depth with values of 0.57 +/- 0.1 mV and 0.29 +/- 0.03 mM respectively. An additional wave with a latency of ca 1 s and a duration of ca 3 s arose on the background of the SPS to a flash stimulus, associated with an additional increase in [K+]0. It is considered that the accumulation of K+ in extracellular space, with neuronal activity, results in depolarization of radial processes of ependymal glia. This is reflected in the neuropil of the upper layers of the optic tectum as an SPS. PMID- 1593504 TI - Communication in the weakly electric fish Sternopygus macrurus. II. Behavioral test of conspecific EOD detection ability. AB - A classical conditioning paradigm was used to test the ability of Sternopygus macrurus to detect EOD-like stimuli (sine waves) of different frequencies. The behavioral tuning curves were quite close in shape to tuning curves based on single-unit recordings of T units, although the sensitivity at all frequencies was much greater. The behavioral curves showed notches of greatly reduced sensitivity when the test frequency was equal to, or twice the EOD frequency. The EOD of each of the fish was eliminated by lesioning the medullary pacemaker nucleus, and the fish were retested. The resulting tuning curves were nearly the same in shape as those of the EOD-intact individuals, but the PMN-lesioned fish showed an overall reduction of sensitivity of 30 dB. The EOD appears to enhance sensitivity by placing the summed stimulus (test stimulus+fish's EOD) at an amplitude where T units are maximally sensitive to small temporal modulations in the fish's own EOD. Peripheral tuning appears to limit the ability of males to detect the EOD of females, since these are, on average, an octave higher in frequency than the male EOD, while the peak sensitivity of the male occurs 5-10 Hz above its own EOD frequency. PMID- 1593503 TI - Communication in the weakly electric fish Sternopygus macrurus. I. The neural basis of conspecific EOD detection. AB - There is a sexual dimorphism in the frequency of the quasi-sinusoidal electric organ discharge (EOD) of Sternopygus macrurus, with males, on average, an octave lower. EODs are detected by tuberous electroreceptor organs, which exhibit V shaped frequency tuning with maximal sensitivity near the fish's own EOD frequency. This would seem to limit the ability of a fish to detect the EODs of opposite-sex conspecifics. However, electroreceptor tuning has always been based on single-frequency stimulation, while actual EOD detection involves the addition of a conspecific EOD to the fish's own. In the present study, recordings were made from single electroreceptive units while the fish were stimulated with pairs of sine waves: one (S1) representing the fish's own EOD added to a second (S2) representing a conspecific EOD. T unit response was easily predicted by assuming that the electroreceptor acts as a linear filter in series with a threshold sensitive spike initiator. P unit response was more complex, and unexpectedly high sensitivity was found for frequencies of S2 well displaced from the fish's EOD frequency. For both P and T units, detection thresholds for S2 were much lower when added to S1, than when presented alone. PMID- 1593505 TI - Cognitive-behavioural problem solving in the treatment of patients attending a medical emergency department: a controlled trial. AB - Previous research has pinpointed high levels of undetected psychiatric and psychosocial problems in medical attenders at an Accident and Emergency department (A&E). In a controlled trial, patients were selected if they fulfilled criteria which had been shown in the previous studies to be associated with high levels of psychopathology and repeat attendance at the A&E department. Patients were randomly allocated to either cognitive-behavioural problem solving treatment, or to a 'treatment as usual' control condition. The use of a brief, home-based treatment and assessments ensured 100% compliance. Results indicated only limited clinical benefits associated with such treatment. The reasons for the limited treatment response are considered; future treatments should be focused and evaluated in specifically defined problem and diagnostic groups. It is concluded that problem solving treatment should be confined to populations in which problem solving deficits have been identified, such as deliberate self harm. PMID- 1593506 TI - Sleep deprivation and the postnatal blues. AB - This prospective study of 63 women was designed to investigate the relationship between sleep disruption prior to the birth, during labour and in the early postpartum period and the subsequent development of the postnatal blues. The results from this preliminary study suggest that two factors: (a) a night-time labour; and (b) a history of sleep disruption in the latter stages of pregnancy, may have aetiological importance in the development of postnatal blues. There was little evidence from this study to suggest that sleep disruption on the nights following the birth, the third sleep factor investigated, had any impact on the expression of the blues. PMID- 1593507 TI - Multidimensional assessment of women's experience of childbirth: relationship to obstetric procedure, antenatal preparation and obstetric history. AB - Primiparous postnatal patients (N = 110) rated their experience of childbirth on a 20-item questionnaire based on an earlier survey of women's spontaneous descriptions. Principal components analysis of the ratings identified three independent dimensions, describing feelings of fulfillment, distress and difficulty, respectively. Ratings by 104 primiparous antenatal patients in the third trimester yielded similar dimensions. The postnatal sample was divided, in turn, according to obstetric procedure at delivery, antenatal classes attended, whether the present pregnancy was planned and history of previous termination. Their experience of childbirth was compared on each dimension. Forceps and unassisted deliveries were experienced similarly. Caesarian section was a less difficult, but also less fulfilling and more distressing, experience than either of these. Delivery was less distressing in those who attended antenatal classes, but only one type of class was associated with more fulfilling birth. Finally, delivery was more distressing in women whose pregnancy was unplanned, or in whom a previous pregnancy had been terminated. Future controlled investigations will be incomplete unless each of the three dimensions is measured. PMID- 1593508 TI - The course of psychiatric disorder associated with non-specific chest pain. AB - One hundred and eight consecutive patients admitted urgently for the first time with chest pain were interviewed to assess psychiatric symptoms prior to admission, at admission and three months later. Seventy-one patients had ischaemic heart disease, 19 had non-specific chest pain and 18 patients were excluded because of other organic causes for the pain. Compared to the ischaemic heart disease subjects, the non-specific chest pain patients tended to have more psychiatric disorder which increased over the three assessments; at follow up 33% of ischaemic heart disease patients and 59% of non-specific chest pain patients had psychiatric disorder. Chest pain was reported by 71% of the non-specific group at three months but this was not related to presence of psychiatric disorder. Unlike previous studies which 'have assessed out-patients with normal coronary angiograms', this study has shown that males predominate among patients admitted urgently with non-specific chest pain. In addition, these subjects use greater amounts of cigarettes and alcohol, and experience significantly more psychiatric disorder compared to patients admitted with ischaemic heart disease. The factors which lead to some of these patients developing chronic non-specific chest pain need to be investigated in further studies. PMID- 1593509 TI - A psychometric study of complaints in chronic tinnitus. AB - Dimensions of psychological complaints due to chronic and disabling tinnitus were investigated by means of the Tinnitus Questionnaire (TQ), administered to a sample of 138 tinnitus sufferers who had been admitted to a psychosomatic hospital. Factor analysis revealed that tinnitus-related patterns of emotional and cognitive distress, intrusiveness, auditory perceptual difficulties, sleep disturbances, and somatic complaints can be differentiated. Cognitive distortions and inappropriate attitudes towards the tinnitus and it's personal consequences were found to be highly intercorrelated forming a subgroup within a broader and more general distress factor. The stability of the factor solution obtained was examined by systematically varying the number of factors to be extracted. Based on the results of this method, scales are proposed for the questionnaire which can be used in clinical and scientific work to specifically assess major areas of tinnitus-related distress and their degree of severity. Implications for a further evaluation of the instrument are discussed. PMID- 1593510 TI - The Rationality/Emotional Defensiveness Scale--II. Convergent and discriminant correlational analysis in males and females with and without cancer. AB - The psychological correlates of the Rationality/Emotional Defensiveness Scale and its two subscales were examined in 1236 males and 863 females from the Western Collaborative Group Study. An additional 157 males and 164 females with some form of cancer other than of the skin were also included in this analysis. Characteristics measured included self-reported emotional control, anger expression, trait personality, depressive and neurotic symptomatology, Type A behavior, hostility, and social desirability. Results indicate that the Rationality/Emotional Defensiveness Scale is most strongly related to the suppression and control of emotions, especially anger. Scores on this scale also tend to be associated with less Type A behavior and hostility and with more social conformity. Analysis of the component subscale suggests that Antiemotionality, i.e. the extent to which an individual uses reason and logic to avoid interpersonally related emotions, is most strongly marked by the control of anger, while Rationality, i.e. the extent to which an individual uses reason and logic as a general approach to coping with the environment, is related to the control of anxiety and a higher level of trait curiosity. The psychological interpretation of the scale appears to be largely invariant across gender, unaffected by residualization of the total scale score for its association with Social Desirability, and, except for a few minor instances, unrelated to the diagnosis of cancer. PMID- 1593511 TI - Efficacy of Tai Chi, brisk walking, meditation, and reading in reducing mental and emotional stress. AB - Tai Chi, a moving meditation, is examined for its efficacy in post-stressor recovery. Forty-eight male and 48 female Tai Chi practitioners were randomly assigned to four treatment groups: Tai Chi, brisk walking, mediation and neutral reading. Mental arithmetic and other difficult tests were chosen as mental challenges, and a stressful film was used to produce emotional disturbance. Tai Chi and the other treatments were applied after these stressors. After all treatments, the salivary cortisol level dropped significantly, and the mood states were also improved. In general the stress-reduction effect of Tai Chi characterized moderate physical exercise. Heart rate, blood pressure, and urinary catecholamine changes for Tai Chi were found to be similar to those for walking at a speed of 6 km/hr. Although Tai Chi appeared to be superior to neutral reading in the reduction of state anxiety and the enhancement of vigour, this effect could be partially accounted for by the subjects' high expectations about gains from Tai Chi. Approaches controlling for expectancy level are recommended for further assessment. PMID- 1593512 TI - The effect of social support and physical touch on cardiovascular reactions to mental stress. AB - To examine the effects of social support on cardiovascular reactions to behavioral stress, the present study tested the relative contribution of three elements of social support: the presence of another person in the laboratory; the presence of a person considered to be a friend; and physical touch. Sixty undergraduate females were assigned to one of the following groups: alone (A); friend present-touch (FT); friend present-no touch (FNT); stranger present-touch (ST); and stranger present-no touch (SNT). Heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) measures were obtained across baseline phases and during presentation of two behavioral challenges (mental arithmetic, mirror-tracing). The findings suggest that neither the presence of a stranger nor physical touch are related to attenuated cardiovascular reactions to stress; rather, if the extent of cardiovascular reactivity is related to social support, the presence of a friend may be the important mediating variable. PMID- 1593513 TI - Habitual somatic discomfort in a representative sample of adolescents. AB - The study is concerned with relations between habitual somatic discomfort, assessed by means of a questionnaire, and indicators of psychosocial adjustment, in a representative sample of 15-16 yr-old Finnish girls (N = 179) and boys (N = 205). Symptom prevalence was associated with anxiety, negative relations with parents, modest plans for education, fear of the future, loneliness, smoking, and drinking. These associations were significant for the boys but not for the girls. High symptom scores also tended to be associated with difficult peer relations (fighting, being target of peers' verbal aggression), and with the use of aggressive and the lack of constructive coping strategies in conflict situations. Boys who often felt lonely and girls who had been involved in physical fights with peers had consistently high scores. Different symptom patterns and sex differences are discussed. PMID- 1593514 TI - Psychophysiological reactions of patients with atopic dermatitis. AB - In a laboratory experiment, 20 female patients with atopic dermatitis (AD) and 20 female controls were exposed to two stress situations (watching a film about scarifications and tatooing, mental arithmetic). Recordings were made of systolic blood pressure, diastolic blood pressure, heart rate, skin conductance level (SCL), number of spontaneous (non-specific) electrodermal fluctuations (SF) and the PSI, the number of active palmar sweat glands in an area of the finger pad. Neither in the cardiovascular variables nor the PSI were any significant group differences found, neither for baseline nor stress values, nor for the response reactions. Atopic dermatitis persons had significantly lower values for SCL and SF throughout the whole experiment, although response reactions did not differ between groups. This study lends no support to the assumption of a general psychophysiological overreactivity or individual specific reactions of the skin system in patients with AD. PMID- 1593515 TI - Seclusion. The nursing challenge. AB - The research to date shows that there is not much data to guide nursing decisions about the use of seclusion. The justification for its use is not always as clear as one might hope. Although many patients are secluded for violence against themselves or others, there are others who have not been violent who are secluded. There may be justification for secluding violent patients, but, as indicated earlier, it may reinforce the behavior it is designed to stop. There probably is no justification for secluding patients who make loud noises, refuse to take medication, or refuse to participate in activities. In addition, it is disconcerting that a large percentage of patients are secluded for "escalating agitation," that is, they have not acted violently against themselves or others. What is problematic is that staff are undoubtedly predicting violent behaviors in these patients--predictions that might be erroneous. Thus, there is ample room for injustice to occur. The potential for injustice is even greater if certain patients are singled out for seclusion or if patients are secluded longer than they or the staff think that they need to be, as is indicated in some of the studies to date. Moreover, if unit variables are associated with seclusion activity, this too, may be indicative of decision making at certain times of the day or by certain staff members that may not be in the best interest of the patient. What seems fairly clear is that secluding a patient is a distressing event for staff and is viewed extremely negatively by some patients and as a reward by others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593516 TI - Psychosocial adaption to pregnancy in prison. AB - 1. Childbearing for incarcerated women is complicated by characteristics of special needs associated with psychosocial adaptation to increased stress, a restrictive physical environment, alteration of social support systems, and the displacement of the maternal role functions after birth. 2. Psychiatric nurses are in a unique position to affect the health care provided for pregnant inmates by virtue of their knowledge and expertise in assessing and treating problems in psychosocial adaptation. 3. Assessment of pregnant inmates is based on identification of the presence and magnitude of dimensions of stress, environmental restrictiveness, social support systems, and maternal role displacement. PMID- 1593517 TI - HIV public service videos offered. PMID- 1593518 TI - Psychodrama alert. PMID- 1593519 TI - A process-oriented approach. Selecting a nursing model for psychiatric nursing. AB - The nursing literature is replete with articles and books that describe nursing conceptual frameworks and models and encourage their use in clinical, education, and research activities. Although much information exists on the content of nursing models, less has been written about how a model is to be chosen and the process that may facilitate the choice of a model. This article reviews potential benefits and limitations of nursing models and conceptual frameworks and describes a three-phase process for selecting a model for psychiatric nursing practice. PMID- 1593520 TI - Oral disease beliefs, behaviors, and health status of Korean-Americans. AB - Previous research with other ethnic minorities has shown that culture and age cohort, as well as language and economic limitations, act as barriers to obtaining dental care and maintaining good oral health. This study compared self reported oral health attitudes, self-efficacy, and dental practices of 20 younger and 23 elderly Korean-Americans. Oral assessments were also conducted to determine plaque and gingival status, and root and coronal caries. Significant differences emerged in health self-efficacy (P less than .01) and preventive health orientation (P less than .002). Elderly had fewer teeth (P less than .0001), more decayed and filled root surfaces (P less than .05 and P less than .004, respectively), and more decayed and filled coronal surfaces (P less than .001 and P less than .03). Both groups showed higher levels of distal and mesial plaque than occlusal and cervical plaque; however, the elderly had higher rates of both (P less than .0001). Gingival status was also worse for the elderly, on distal and mesial (P less than .01), facial (P less than .01), and lingual (P less than .01) surfaces. These differences are striking, since the elderly reported visiting the dentist more recently (P less than .0001); but most of these visits were for prosthodontic and emergency care. Better preventive dental care and education are necessary for elderly immigrants who have not been exposed to preventive dentistry in their home countries. PMID- 1593522 TI - Statistical methodologies useful for the analysis of data from risk-assessment studies. AB - In dentistry, the vast majority of studies attempting to predict who is at high risk for getting a disease or condition, or attempting to identify risk factors for a specific disease or condition, have focused either on only one risk factor at a time, or have measured multiple potential risk factors, but analyzed their effects in isolation. Since researchers tend to agree that most dental conditions have a multiple etiology, it is necessary to develop models that consider simultaneously the effect of a number of potential risk factors on the disease or condition of interest if we are to have any understanding of the relative impact of potential risk factors. Many existing statistical techniques will aid dental researchers in identifying risk factors. However, the selection of an appropriate analytic technique depends on a number of conditions. The strategy for this paper is to discuss a wide range of possible statistical techniques that may be applied to the problem of deriving a model for identification of multiple risk factors for dental diseases and conditions. We have approached this task by presenting a number of dental research problems needing an appropriate analytic technique. Next, basic issues that must be considered in choosing an appropriate analytic strategy are discussed. These issues include features of the study design, the data structure of the variables being measured, and the types of assumptions that are applicable to provide valid inferences about the target population of interest. A matrix of possible analytic techniques is presented for various combinations of study-design and data-structure features. After a discussion of each of the techniques, the appropriate statistical techniques for each of the dental examples are described. The issues and examples presented in this paper should be of use to dental researchers who wish to investigate multiple risk factors for a disease or condition of interest. PMID- 1593521 TI - Factors associated with parental acceptance of dental sealants. AB - Whereas a number of surveys have documented oral disease preventive behaviors and associated factors, little is known about public knowledge and beliefs about dental sealants. In this study, factors associated with the presence of sealants were studied in first and second graders residing in Columbia, SC. From a sample of 1,119 children, 88 were found clinically to have sealants; 508 did not have, but needed them. Parents of the sealant children (n = 87) and of a random sample of the no-sealant children (n = 289) were interviewed by telephone to obtain information regarding (1) factors related to parents' inclination to obtain sealants for their children, (2) ability of the family to obtain oral disease preventive services, and (3) the influence of others in the family's decision making efforts. Analysis of 16 factors thought to be related to sealant presence revealed that parents were more likely to obtain dental sealants for their children if dentists or their staffs recommended them, if the parents were knowledgeable about dental sealants, if the parents were more highly educated, and if the parents had dental insurance coverage. Parents were less likely to obtain dental sealants for their children if they heard about them from mass media. The latter finding is unexpected and may have been influenced by conflicting or negative opinion expressed by some dental practitioners through mass media or other channels of communication.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593523 TI - Dental lessons learned: communication works. PMID- 1593525 TI - AAPHD Graduate Student Merit Awards for outstanding achievement in dental public health. PMID- 1593524 TI - AAPHD Student Merit Awards for outstanding achievement in community dentistry. PMID- 1593526 TI - Special Merit Award: Dr. Daniel F. Whiteside. PMID- 1593527 TI - Public Service Award: Ms. Kay Johnson. PMID- 1593528 TI - Distinguished Service Award: Dr. Irwin D. Mandel. PMID- 1593529 TI - Partners for prevention: remarks upon receiving the 1991 Distinguished Service Award of the AAPHD. PMID- 1593530 TI - Effect of bovine serum albumin on motility and fecundity of turkey spermatozoa before and after storage. AB - Motility characteristics of turkey spermatozoa before and after storage for 24 h at 7 degrees C in diluent with and without bovine serum albumin (BSA; 1% final concentration) were measured by computer-assisted semen analysis. BSA significantly increased the percentage of motile spermatozoa and sperm velocity, linearity, lateral head displacement and beat frequency in each treatment, but BSA in fresh or stored semen in diluent did not augment hen fertility over 15 weeks of egg production. Fatty-acid-free BSA, globulin-free BSA and Fraction V BSA all significantly increased each sperm motility characteristic compared with semen in diluent alone. The lack of correlation between sperm motility and fecundity emphasizes the need to develop procedures for semen evaluation that accurately predict the fertilizing capacity of an aliquot of semen. PMID- 1593531 TI - Maturation and regulation of the motility of spermatozoa in the epididymis of the tammar wallaby (Macropus eugenii). AB - Demembranated spermatozoa from the rete testis developed vigorous flagellation when reactivated with ATP, but showed no forward progression such as that seen in samples from the cauda epididymidis. The proportion of spermatozoa that were reactivated was smaller for samples from the rete testis than from the cauda epididymidis. Studies in vitro of undiluted micropuncture samples from the epididymis indicated that the activity of spermatozoa is suppressed as they develop the capacity for motility. However, as spermatozoa spontaneously became activated during the collection or subsequent incubation of undiluted samples, it was concluded that the suppressive action is labile. The activity of spermatozoa in vitro was examined in diluted samples from the cauda epididymidis. A concentration of 2.5 mmol extracellular calcium/l was better than lower concentrations. Diluents at pH 5.5 completely inhibited sperm motility when they contained 20 mmol lactate/l (but not glutamate) and the effect was reversed by readjusting the diluent to pH 7.4. However, lactate was not considered to suppress sperm motility in situ, as the plasma from the cauda epididymidis contained only 2.7 +/- 0.5 mmol lactate/l. There was no effect of sodium concentration (1 and 115 mmol/l), pH (5.5 and 7.4) or amiloride (0 and 1 mmol/l) on sperm motility, indicating that motility is not dependent on the concentration of sodium above 1 mmol/l or on a sodium-proton exchange system. The relative viscosity of plasma from the cauda epididymidis did not affect the motility of spermatozoa. PMID- 1593532 TI - Change in responsiveness of rabbit corpus luteum to prostaglandin F-2 alpha during pregnancy and pseudopregnancy. AB - Previous studies have suggested that prostaglandin F-2 alpha (PGF-2 alpha) may have a role in luteolysis in rabbits. Rabbits (4-6/group) were given a single injection of saline, or 100, 500 or 2500 micrograms PGF-2 alpha (i.m.) on Day 7, 9, 12 or 15 of pregnancy or pseudopregnancy. Daily blood samples were taken via the marginal ear vein before and for 3 days after the PGF-2 alpha injection. Concentrations of serum progesterone were determined by radioimmunoassay in pseudopregnant rabbits. There were no significant differences between PGF-2 alpha treated and control rabbits on Days 7 or 9. On Day 12 of pseudopregnancy, progesterone concentration was significantly (P less than 0.05) lower in treated than in control rabbits, the effect being dose dependent. On Day 15 of pseudopregnancy, it was not possible to distinguish between controls and treated groups because luteolysis occurred in all rabbits. In contrast, on Days 7 and 9 of pregnancy, the concentration of progesterone in treated groups was lower than in the control groups (P less than 0.05), the effect being dose dependent. This difference was maintained throughout the sampling period and resulted in termination of pregnancy. By Day 12 of pregnancy, the response to PGF-2 alpha was transient, with a significant decline in progesterone for only 2 days, followed by a return to control concentrations and normal delivery of litters. On Day 15 of pregnancy, no treatment with PGF-2 alpha significantly altered progesterone concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593533 TI - Localization of prostaglandin F2 alpha inhibition of lipoprotein use by bovine luteal cells. AB - Prostaglandin F2 alpha (PGF2 alpha) inhibits lipoprotein-stimulated progesterone production by bovine luteal cells in vitro and the objective of this study was to localize the site of action of PGF2 alpha. Cultured bovine luteal cells were treated with PGF2 alpha for seven days, and then with either lipoproteins or 25 hydroxycholesterol in the presence of aminoglutethimide (which inhibits cholesterol side-chain cleavage) for the final 48 h. The effects of PGF2 alpha on progesterone production, cellular cholesterol content, mitochondrial cholesterol content and cholesterol side-chain cleavage activity were determined. As expected, PGF2 alpha inhibited (P less than 0.05) lipoprotein-stimulated progesterone production. However, PGF2 alpha did not inhibit low-density lipoprotein-stimulated, or high density lipoprotein-stimulated, increases in cellular cholesterol (P less than 0.05) or inhibit lipoprotein-induced increases in mitochondrial cholesterol content (P less than 0.05). Additionally, cholesterol content of mitochondria increased (P less than 0.05) in the presence of PGF2 alpha alone. To determine if the PGF2 alpha-induced inhibition of steroidogenesis occurred at, or after, the side-chain cleavage reaction, we treated cells with the readily diffusable sterol, 25-hydroxycholesterol. Prostaglandin F2 alpha did not inhibit 25-hydroxycholesterol-stimulated progesterone production (P less than 0.05). Prostaglandin F2 alpha may therefore exert its luteolytic effect at a site after cholesterol transport to the mitochondria but before cholesterol side-chain cleavage. PMID- 1593534 TI - Luteal function after intrauterine infusion of recombinant bovine interferon alpha I1 into postpartum beef cows expected to have short or normal luteal phases. AB - This study was conducted to determine whether intrauterine infusion of recombinant bovine interferon-alpha I1 (rboIFN-alpha I1), which has 70% sequence identity to bovine trophoblast protein-1, will prevent regression of corpora lutea anticipated to have a short lifespan. Twenty-six beef cows in good body condition were allotted to four treatment groups at parturition in a 2 x 2 factorial design. Treatments were: group 1, saline; group 2, rboIFN-alpha I1; group 3, norgestomet-saline; and group 4, norgestomet-rboIFN-alpha I1. Norgestomet implants were inserted on days 21-24 postpartum and removed 9 days later (before injection of human chorionic gonadotrophin (hCG)). Ovulation was induced 30 to 33 days postpartum with 5000 or 10,000 iu hCG. Groups 1 (n = 7) and 3 (n = 5) were given intrauterine infusions (rectocervical approach) twice daily with saline on days 1-12 or 13-24 after hCG injection, respectively. Cows allotted to groups 2 (n = 8) and 4 (n = 6) were given intrauterine infusions (rectocervical approach) of 2 mg rboIFN-alpha I1 twice daily on days 1-12 or 13 24 after hCG injection, respectively. Treatment with both norgestomet and rboIFN alpha I1 delayed (P less than 0.01) luteolysis. Lengths of luteal phases (days; mean +/- SEM) were 8.4 +/- 0.7 (group 1, saline), 14.1 +/- 1.0 (group 2, rboIFN alpha I1), 18.6 +/- 1.3 (group 3, norgestomet-saline) and 20.8 +/- 1.2 (group 4, norgestomet-rboIFN-alpha I1). Concentration of progesterone in serum was similar among all groups the first 6 days following hCG-induced ovulation, but differed (P less than 0.01) thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593535 TI - Spermatogenesis in retinol-deficient rats maintained on retinoic acid. AB - Rats maintained on a diet deficient in retinol and retinoic acid were given a diet containing retinoic acid for 21-29 days after the start of weight loss. The testes of four of these rats were studied. Spermatogonia of all types were observed, though in lower numbers than in controls, and their mitotic activity was normal. Normal preleptotene spermatocytes were encountered, but no normal spermatocytes in further stages of development were seen. Pale cells that appeared to be in prophase were observed. It was concluded that, in retinol deficient rats maintained on retinoic acid, the spermatogonial population is qualitatively normal, but quantitatively subnormal, while spermatocyte development is qualitatively and quantitatively abnormal. No evidence of spermatogonial arrest or any other form of synchronization was found in testes of these rats, but when the remaining rats were injected with retinol, the seminiferous epithelium did show stage synchronization at 36 and 128 days after the injection. PMID- 1593536 TI - Effects of heating the testes and epididymides of rams by scrotal insulation on fertility and embryonic mortality in ewes inseminated with frozen semen. AB - Fertilization rate and embryonic mortality were assessed in 636 ewes inseminated in each uterine horn with 50 x 10(6) frozen spermatozoa from four control rams and from four rams submitted to a moderate (1.4-2.2 degrees C), but repeated, intermittent (16 h/day for 21 consecutive days) increase in their subcutaneous scrotal temperature by means of scrotal insulation. Pregnancy was assessed twice in each ewe from concentration of progesterone in blood plasma at 17 days and by ultrasound at 65 days after insemination. No differences were observed in the pregnancy rate at 17 days between ewes inseminated with semen collected from control rams (56.0, 65.2, 66.7 and 60.3%) and from heated rams (60.6, 71.8, 63.6 and 48.2%) before or after 4, 15 and 21 days of heating, respectively. In contrast, the rate of embryonic mortality between 17 and 65 days after insemination was significantly higher at days 4, 15 and 21 in the heated rams (78.7, 78.6 and 93%) than in the control rams (55, 59 and 65.7%). These results indicate that an intermittent slight, but repeated, increase in the subcutaneous scrotal temperature could induce a significant increase in the embryonic mortality rate. As these changes were apparent on day 4 of heating, an effect must have occurred on sperm stored in the epididymis. PMID- 1593537 TI - Increased flow of testicular blood plasma during local heating of the testes of rams. AB - After removal of the scrotal skin, one testis of each of 12 adult anaesthetized rams was kept at 33 degrees C for 60 min, then heated either to 36 degrees C for 60 min and then to 39 degrees C for 60 min, or to 36 degrees C for 120 min and then returned to 33 degrees C for 100 min, while the other testis was maintained at 33 degrees C. Flow of testicular blood plasma was measured every 10 min using the technique of dilution of sodium p-aminohippurate. When the temperature of the testis was raised to 36 degrees C, flow of blood plasma gradually increased and reached a higher than normal rate at the end of the first hour, without any further increase during the second hour. The increase in mean flow rate was 25.8 +/- 3.4% (mean +/- SEM) during the second hour at 36 degrees C, and 77.1 +/- 12.8% during the hour at 39 degrees C, compared with the respective values at 33 degrees C. No significant changes were seen in testicular lymph flow determined by collection for 10 min in four rams at 36 degrees C (60 min) and then at 39 degrees C (60 min). These results are different from those from earlier studies in which total blood flow was unchanged when the scrotum and testes were heated. The difference could be related either to lack of heating of the scrotum or to the lower temperatures used in the present study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593538 TI - Effect of progesterone and oestradiol benzoate on oestrous behaviour and secretion of luteinizing hormone in ovariectomized fallow deer (Dama dama). AB - Eighteen ovariectomized fallow deer does and two adult bucks were used to investigate the effect of exogenous progesterone and oestradiol benzoate on oestrous behaviour and secretion of luteinizing hormone (LH). In Expts 1 and 2, conducted during the breeding season (April-September), does were treated with intravaginal Controlled Internal Drug Release (CIDR) devices (0.3 g progesterone per device) for 12 days and differing doses of oestradiol benzoate administered 24 h after removal of the CIDR device. The dose had a significant effect on the proportion of does that exhibited oestrus within the breeding season (P less than 0.001), the incidence of oestrus being 100% with 1.0, 0.1 and 0.05 mg, 42% for 0.01 mg and 0% for 0.002 mg oestradiol benzoate. There was a significant log linear effect of dose on the log duration of oestrus, which was 6-20, 2-14, 2-12 and 2 h after treatment with 1, 0.1, 0.05 and 0.01 mg of oestradiol benzoate, respectively. Dose had a significant effect on the peak plasma LH concentration (P less than 0.01), mean (+/- s.e.m.) surge peaks of 27.7 +/- 2.3, 25.9 +/- 1.8 and 18.6 +/- 3.4 ng/ml being observed following treatment with 1, 0.1 and 0.01 mg oestradiol benzoate respectively. In Expt 3, also conducted during the breeding season, progesterone treatment (0 vs. 6-12 days) before the administration of 0.05 mg oestradiol benzoate had a significant effect on the incidence of oestrus (0/6 vs. 10/12, P less than 0.05), but not on LH secretion. The duration of progesterone treatment (6 vs. 12 days) had no effect on oestrus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593539 TI - Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause. AB - To obtain more insight into the relationship between cyclic and regional changes in steroid receptor expression and function-related changes in the various types of cell of the normal human uterus, we performed an immunocytochemical study on paraffin-embedded sections. The distribution and intensity of immunostaining for the oestrogen receptor and the progesterone receptor in the various types of cell were semiquantitatively scored. The data were statistically compared for the different phases of the menstrual cycle and after the menopause, and for the different regions of the corpus and (endo)cervix uteri. During the menstrual cycle, significant changes in oestrogen receptor score were observed in glandular and stromal cells of endometrium basalis and functionalis and in smooth muscle cells of the myometrium. In all types of cell, oestrogen receptor expression reached a maximum in the late proliferative phase. During the early secretory phase, oestrogen receptor staining declined sharply in stromal and smooth muscle cells, whereas, in glandular epithelium, oestrogen receptor expression decreased more gradually. During mid- and late-secretory phases, an increase in oestrogen receptor staining was also observed in predecidualizing stromal cells and smooth muscle cells. Progesterone receptor numbers changed significantly in glandular epithelium but not in stromal and smooth muscle cells. Glandular progesterone receptor expression reached a maximum in the early secretory phase and was then drastically reduced. During mid- and late-secretory phases stromal cells were moderately stained for progesterone receptor in contrast to epithelial gland cells which showed no or very weak staining. No regional variations in steroid receptor distribution in endometrium and myometrium were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593540 TI - Positive effect of taurine on preimplantation development of mouse embryos in vitro. AB - The effect of various taurine concentrations in modified Tyrode's medium on in vitro fertilization of mouse oocytes was examined. No significant difference in fertilization rate was found at concentrations of 0, 0.1, 1, 5, 10 and 20 mM taurine. In a second series of experiments, the effect of taurine on preimplantation embryonic development after fertilization in vitro was studied. At concentrations of 1, 5, 10 and 20 mM taurine, significantly more two-cell embryos reached the blastocyst stage compared with medium without taurine. Culture in the presence of 5 mM or 10 mM taurine resulted in blastocysts with the highest mean number of cells. The positive effect of taurine on embryonic development was found to be more pronounced both in a second medium (human tubal fluid medium) which has a higher potassium concentration than Tyrode's medium, and in a modified Tyrode's medium with an increased potassium concentration. In addition to these in vitro studies, it is reported that taurine comprised about 59% of the total free amino acid content in mouse oviduct flushings, compared with 17% in mouse serum. PMID- 1593541 TI - Effect of intrauterine application of oestradiol-17 beta and prostaglandin E-2 on the porcine oestrous cycle and uterine endocrinology. AB - Silastic beads were inserted into the uterine lumen on Day 10 after oestrus. Gilts received beads containing oestradiol-17 beta only, oestradiol benzoate, or oestradiol-17 beta+prostaglandin (PG) E-2. Oestrous cycles were slightly longer in treated than in untreated pigs (20.2 +/- 0.4 days), and durations were 22.6 +/ 1.3, 26.2 +/- 1.7 and 23.2 +/- 1.8 days for oestradiol-17 beta, oestradiol benzoate and oestradiol-17 beta+PGE-2 treatments, respectively (P greater than 0.05). Thus, PGE-2 and an oestrogen such as oestradiol benzoate that persist for a longer period cannot prolong the cycle more than oestradiol-17 beta alone. Additional cyclic gilts underwent similar treatments with beads containing oestradiol-17 beta, oestradiol-17 beta+PGE-2 or cholesterol, and cannulation of one utero-ovarian vein on Day 10. Blood samples were collected from the catheter every 15 min from 08:00 until 11:00 h and from 20:00 until 23:00 h for 5 consecutive days starting the day after surgery and peripheral plasma samples were also collected daily. On Day 16, beads containing oestradiol-17 beta were surrounded by endometrial folds whereas cholesterol beads were free. Concentrations of plasma progesterone did not vary significantly from Days 11 to 16 in gilts treated with oestradiol-17 beta or oestradiol-17 beta+PGE-2, but decreased in cholesterol-treated gilts. Concentrations of plasma oestrone and oestradiol-17 beta were more than ten times higher in gilts treated with oestradiol-17 beta or oestradiol-17 beta+PGE-2 than in cholesterol-treated gilts on the day after bead insertion, but decreased rapidly to values comparable to those in cholesterol-treated gilts by Day 14. In contrast, concentrations of oestrone sulphate remained high until Day 16. Concentrations of PGE-2 in the utero-ovarian vein plasma did not differ (P greater than 0.05) between treatments but those of PGF-2 alpha were higher (P less than 0.004) in gilts treated with cholesterol than in those treated with oestradiol-17 beta or oestradiol-17 beta+PGE-2. It is postulated that insufficient oestradiol-17 beta is released by the beads toward the end of a 'recognition period' to prolong the cycle for more than 3-6 days. PMID- 1593542 TI - Regulation of insulin-like growth factor I binding in the rat uterus by growth hormone and thyroxine. AB - The insulin-like growth factor-I (IGF-I)-binding sites in the rat uterus were characterized further and the effects of growth hormone and thyroxine examined. The 125I-labelled IGF-I binding sites on uterine membranes demonstrated relative binding affinity of less than 20% for IGF-II, less than 1% for insulin and no affinity for an unrelated peptide, epidermal growth factor, compared with 100% for IGF-I confirming the specificity of these binding sites. Scatchard analysis of the specific binding data revealed the presence of a single class of high affinity binding sites (Kd = 2.50 +/- 0.68 nmol l-1, with a binding capacity of 1.02 +/- 0.13 pmol mg-1 membrane protein in the uterus of the pituitary-intact ovariectomized rat. After hypophysectomy, the uteri from these rats had significantly (P less than 0.05) increased IGF-I binding sites, without significant changes in their affinity. Administration of growth hormone with or without L-thyroxine reversed this increase in IGF-I binding. Injection of thyroxine alone to the hypophysectomized ovariectomized rats had no significant effects on the uterine IGF-I binding sites. These data show that growth hormone, but not thyroxine, can regulate IGF-I binding sites in the rat uterus, possibly through regulating IGF-I production. PMID- 1593543 TI - Concentrations of luteinizing hormone and oestradiol in plasma and response to injection of gonadotrophin-releasing hormone analogue at selected stages of anoestrus in domestic bitches. AB - Concentration of plasma luteinizing hormone (LH) and oestradiol concentrations and responses to a standard challenge with a gonadotrophin-releasing hormone (GnRH) analogue were measured at certain stages of anoestrus during consecutive cycles in five beagle bitches. Blood samples were collected every 20 min for 6h followed immediately by injection of GnRH analogue (0.16 micrograms i.v.) and collection of further samples after 10, 20, 40 and 60 min. Five, 10, 17 and three such sampling sequences were obtained during the luteal phase, transition to anoestrus, anoestrus and pro-oestrus respectively (i.e. 154-71, 114-44, 85-11 and 7-1 days before the preovulatory LH peak, respectively). Pulsatile LH secretion occurred spontaneously at all stages of the luteal phase and anoestrus and there was no effect of cycle stage on mean LH concentration or variability. In contrast, oestradiol could not be detected in most samples from early and mid anoestrus until approximately one month before the preovulatory LH peak, after which average oestradiol concentration and between sample variability appeared to increase. Mean (+/- SEM) oestradiol concentration for all samples collected from 100-75, 74-50, 49-25, 24-10 and 9-1 days before LH peak was 1.4 +/- 0.1, 1.3 +/- 0.1, 2.4 +/- 0.3, 11.0 +/- 1.4 and 36.0 +/- 3.2 pg ml-1, respectively. Plasma LH concentration increased in all bitches after GnRH analogue injection (2.7 +/- 0.7 ng ml-1 at t = 0, 12.5 +/- 1.0 ng ml-1 at t = 10 min, mean +/- SEM, n = 35) regardless of cycle stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593544 TI - Seasonal variation in cell cycle during early development of the mouse embryo. AB - Studies of the cell cycle of mouse embryos before implantation were conducted using Giemsa and DAPI stains. The time of embryo recovery did not affect the success rate of cultures during the winter, but embryos cultured during the summer showed the 'two-cell block' phenomenon at the early two-cell stage, 30-37 h after the injection of human chorionic gonadotrophin. There was no significant difference in the number of embryos collected per mouse between summer and winter, but cleavage from the two-cell to the four-cell stage occurred later in the summer than in the winter. Cell cycle of mouse embryos may therefore show seasonal variation. PMID- 1593545 TI - Origin of reactive oxygen species in human semen: spermatozoa or leucocytes? AB - Peroxidative damage induced by reactive oxygen species (ROS) has been proposed as one of the major causes of defective sperm function. In previous studies of the production of ROS in semen, the contribution of contaminating leucocytes was not assessed. We determined the levels of ROS in 60 semen samples from men attending our infertility clinic and demonstrated by performing extraction experiments with antibody-coated magnetic beads that, within this unselected population of patients, leucocytes were the major source of ROS in the low-density Percoll fraction. Of the sperm motion parameters examined using computerized semen analysis, beat-cross frequency was the only one significantly affected by the ROS in semen. PMID- 1593546 TI - Purification of an embryotrophic factor from commercial bovine serum albumin and its identification as citrate. AB - A factor of low M(r) with growth-promoting effects on rabbit embryos was extracted and purified from commercial bovine serum albumin (BSA). This embryotrophic factor was extracted from BSA dissolved in formic acid by membrane filtration (membrane cutoff of M(r) 10,000) and then freeze-drying of the filtrate. The extract was purified successively by chromatography on G-10 Sephadex, QAE-Sephadex A-25 anion exchange and high-performance liquid chromatography (HPLC) reverse-phase columns. Mass spectrometry of the active reverse-phase material indicated that the major component in this material had an M(r) of 192. The embryotrophic factor in the low M(r) extract of BSA was shown to be citrate, because: (i) the mass spectra of the active reverse-phase material and citrate were identical, (ii) the activity was eluted at the identical position to citrate on an analytical HPLC anion-exchange column, (iii) the original BSA sample was shown by enzyme assay to be heavily contaminated by citrate and (iv) citrate stimulated cell proliferation and expansion of blastocysts. PMID- 1593547 TI - Development of mouse enucleated oocytes receiving a nucleus from different stages of the second cell cycle. AB - The influence of the stage of the cell cycle of donor nuclei on the development of mouse oocytes enucleated at telophase I was examined. After nuclear transplantation and activation, a high proportion of the oocytes remodelled a nucleus, emitted a polar body and formed a pronuclear-like nucleus. Most of the reconstituted embryos that received an interphase nucleus 30-32 h or 34-36 h after treatment with human chorionic gonadotrophin (hCG) arrested at the 2-cell stage. The reconstituted embryos were able to develop to blastocysts when nuclei from late 2-cell embryos (44-46 and 48-50 h after hCG) were transferred to the oocytes. The resulting blastocysts were transferred to recipients and ten live young were obtained from the embryos that formed a pronuclear-like nucleus after extrusion of a polar body. Thus, the developmental ability of the reconstituted embryos was critically influenced by the stage of the cell cycle of the donor nuclei. PMID- 1593548 TI - Effects of time after ovariectomy, season and oestradiol on luteinizing hormone and follicle-stimulating hormone secretion in ovariectomized ewes. AB - During the breeding season, five groups of three ewes were implanted at ovariectomy with 0.36, 0.5, 1.0 and 6.0 cm oestradiol implants or implants containing no steroid. Eleven days after receiving implants, blood samples were taken every 10 min for 6 h; implants were then removed. Treatments were repeated three times during each of two consecutive breeding seasons and four times during the intervening anoestrus. In ovariectomized ewes without steroid treatment, luteinizing hormone (LH) pulse frequency increased from early to mid-breeding season, decreased to a minimum at mid-anoestrus and increased to reach a maximum at the mid-point of the second breeding season, subsequently declining. LH pulse amplitude was inversely related to frequency. Basal serum LH concentrations decreased gradually from the first breeding season to reach a minimum at mid anoestrus and gradually increased to reach a maximum at the end of the second breeding season. Mean serum LH and follicle-stimulating hormone (FSH) concentrations were higher at the end of the second breeding season compared with the beginning of the first breeding season. All parameters of gonadotrophin secretion were decreased much more by oestradiol during the anoestrus than during the breeding season. LH pulse frequency was decreased during anoestrus and at high oestradiol concentrations during the first breeding season. Apart from LH pulse amplitude, the decreases in all parameters of gonadotrophin secretion were less during the second compared with the first breeding season. The minimum effective dose of oestradiol required to decrease mean and basal serum concentrations of LH during anoestrus was lower than in the breeding season. The minimum effective dose of oestradiol required to decrease mean serum concentrations of FSH was lower in the first compared with the second breeding season. Oestradiol depression of LH pulse amplitude and mean serum concentrations of LH and FSH showed a dose dependency during the breeding season. During anoestrus dose dependency was seen for basal concentrations of LH and mean serum concentrations of LH and FSH. We conclude that significant chronic changes in gonadotrophin secretion occur in the ewe with time after ovariectomy. Sensitivity to oestradiol also changes, and the effects of oestradiol are not always dose dependent. We suggest that the circannual pattern of LH pulse frequency and basal LH secretion are directly linked to the circannual cycle of photoperiod.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1593549 TI - Oxygen consumption and evaporation during parturition in a vespertilionid bat (Pipistrellus pipistrellus). AB - Oxygen consumption and evaporation were measured in a single pregnant pipistrelle bat during labour and parturition of twins, using an open-flow respirometry system. During 233 min of measurements, three distinct phases were noted, which we suggest represent prelabour, labour and grooming or suckling the young. On the basis of this hypothesis, during labour and parturition, oxygen consumption was a maximum of 8.9% of daily energy expenditure, evaporation was 2.7% of daily water turnover, and total water loss was 5.5% of daily water turnover in free-living bats in early lactation. We estimated that, for the mother and young combined, oxygen consumption associated with grooming and suckling would be equivalent to 37.5% of daily energy expenditure of the mother, if carried out continuously. Similarly, evaporation due to grooming and suckling would be equivalent to 16.4% of daily water turnover. In terms of daily energy expenditure and daily water turnover, labour and parturition are therefore cheap, but grooming and suckling (even ignoring costs in terms of losses in the milk) are expensive. PMID- 1593550 TI - Hysteroscopy. AB - Hysteroscopy is a "new" endoscopic approach for the gynecologist. The development and refinement of the sophisticated fiberoptic light system can illuminate the darkness of the uterine cavity. Polyps can be differentiated from submucous myomas; intrauterine adhesions can be accurately "mapped" and classified, with synechiae lysed under direct vision; endometrial carcinoma can be diagnosed and possibly staged; embedded intrauterine devices can be identified and dislodged; the wastebasket diagnosis of "dysfunctional uterine bleeding" can be cleaned up; submucosal myomas and uterine septa can be resected; and successful transuterine sterilization may become a reality. If culdoscopy is menopausal and laparoscopy in its reproductive years, hysteroscopy is certainly in its infancy. PMID- 1593551 TI - Outpatient loop diathermy conization as an alternative to inpatient knife conization of the cervix. AB - A knife cone biopsy of the cervix is usually performed as an inpatient procedure under general anesthesia and is associated with significant morbidity. Loop diathermy conization was performed under local anesthesia on colposcopy outpatients as an alternative to knife conization. In 33 consecutive patients studied the procedure was well tolerated, there were no operative complications, and a satisfactory specimen for histologic examination was obtained in every case. One case of unsuspected invasive cancer and two of suspected microinvasive cancer were diagnosed. The diagnosis of cervical precancer was made in 24 (73%) of the cases. The introduction of outpatient loop diathermy conization of the cervix instead of knife conization would decrease hospitalization costs, avoid the need for general anesthesia and potentially reduce short-term patient morbidity. PMID- 1593552 TI - Effect of intraumbilical prostaglandin F2 alpha injection on the third stage of labor. AB - The effect of an intraumbilical prostaglandin (PG) F2 alpha injection on the third stage of normal labor was studied in 54 normal, laboring women at term. Either 1 mg of PGF2 alpha diluted to 20 mL in normal saline (27 women) or 20 mL of normal saline alone (27 women) was injected into the umbilical vein immediately after delivery using a randomized, double-blind protocol. The mean (+/- SD) duration of the third stage was 7.31 +/- 6.37 minutes in the PGF2 alpha patients and 8.94 +/- 7.10 in the normal saline patients. Intraumbilical PGF2 alpha did not influence the third stage of normal labor. PMID- 1593553 TI - Prostaglandin for enhancing bladder function after vaginal surgery. Does it work? AB - Fifty women underwent vaginal hysterectomy with or without anterior and posterior colporrhaphy. After the operations the women were allocated randomly to one of three groups. One group (17 patients) received daily vaginal suppositories of 10 mg of prostaglandin E2. The second group (15) received a daily intravesical solution of 50 micrograms of prostaglandin F2 alpha dissolved in 100 mL of normal saline. The third group (18) received a daily instillation of 100 mL of saline and served as the control group. The postvoiding residual urinary volume was checked daily through a suprapubic catheter, which was removed once the residual volume was less than 50 mL. The prostaglandin did not shorten the time required for postoperative bladder drainage. The rates of febrile morbidity and hospital stay were the same in all three groups. Since most of the women in the study voided spontaneously within three days, the "sit and wait" approach seems reasonable in such patients, and prophylactic treatment to enhance bladder function after vaginal operations does not seem justified. PMID- 1593554 TI - Abdominal sacral colpopexy in 163 women with posthysterectomy vaginal vault prolapse and enterocele. Evolution of operative techniques. AB - Abdominal sacral colpopexy with retroperitoneal interposition of a suspensory hammock between a prolapsed vaginal vault and the anterior surface of the sacrum was performed on 163 women for correction of vaginal vault prolapse during 18 consecutive years, from 1972 through 1989. Hysterectomy had previously been performed on 160 of the patients, 2 patients had congenital absence of the uterus, and 1 patient underwent vaginal hysterectomy at the time of the sacral colpopexy. The patients had been followed for 9 months to 18 years at this writing, with a median follow-up of 33 months. An additional 25 patients underwent successful sacral colpopexy since the end of the study period, but those data are not included here. Modifications of surgical techniques have evolved from our experience. PMID- 1593555 TI - Twin pregnancy. Ultrasonographically observed changes in fetal presentation. AB - The changes in fetal presentation throughout pregnancy were observed ultrasonographically in 332 sets of twins. Seventy-eight percent of the leading twins were vertex at 26-30 weeks' gestational age, 75% at 31-34 weeks and 81% at 35-38 weeks. The incidence of nonvertex presentation for either twin was 73.0%, 64.5% and 59.5% at the same gestational ages. The results are not significantly different from those on concordant twins delivered at the same gestations. Thus, one can counsel parents of twins at all gestational ages in regard to the potential for malpresentation. PMID- 1593556 TI - Incidence of bacteremia at dilation and curettage. AB - The American Heart Association does not recommend prophylactic antibiotics for patients undergoing dilation and curettage (D & C) except in the case of septic abortion or the presence of prosthetic valves. This recommendation is based on a retrospective analysis of case reports of infectious complications of D & C. To date we are unaware of prospective studies that answer this question. At a community hospital we studied 20 patients undergoing D & C for noninfectious indications. Aerobic and anaerobic blood cultures were performed before and during the D & C. All baseline cultures were negative. In one patient we were able to isolate Lactobacillus after the D & C, thus finding a 5% incidence of bacteremia. That places D & C in the same risk category as other diagnostic procedures considered low risk in the pathogenesis of subacute bacterial endocarditis. Our study thus validated the recommendations made by the American Heart Association. PMID- 1593557 TI - Labor in the gravida with 10 or more years between pregnancies. AB - It has been suggested that women who have had a pregnancy interval of 10 or more years would have prolonged labor in pregnancies after the first, as do primigravidas. In a series of 94 multiparas with 10 or more years between pregnancies and 63 age-matched, multiparous controls, there was no significant difference in the length of the latent phase of labor or of the first, second and third stages of active labor in the two groups. The concept of a "physiologic primigravida" in these cases should be abandoned. PMID- 1593558 TI - A woman's attitude toward pregnancy. Can it predispose her to preterm labor? AB - A prospective study was designed to assess the relationship between a woman's attitude toward pregnancy, sociomedical factors and preterm labor among 434 consecutive pregnant women who filled out a self-reporting, multiple choice questionnaire at 24-28 weeks' gestation. The score on "poor investment in pregnancy," evaluating the maternal attitude toward pregnancy and the antepartum fetomaternal relationship, was the best predictor of preterm labor, followed by the risk score based upon sociomedical factors. Psychologic factors could play a significant role in the onset of preterm labor. PMID- 1593559 TI - Recurrent vaginal candidiasis. Results of a cohort study of sexual transmission and intestinal reservoir. AB - Yeast cultures from the oral cavity, vagina and rectum were obtained from 125 women experiencing an acute episode of recurrent candidal vaginitis. To investigate the role of sexual transmission, oral, penile and ejaculate cultures were also prepared from all the male sexual partners. The rates of oral and rectal Candida species colonization in the women were 36% (45/125) and 44.8% (56/125), respectively. The male partners' oral cavities were positive in 23.2% (29/125) and the penile coronal sulcus and seminal fluid in 16% (20/125) and 14.4% (18/125), respectively. The susceptibility of the isolated species to the main antimycotic drugs was ascertained with the agar diffusion method. Therapy in the women and the colonized sexual partners was carried out, eliminating the microorganism from every positive site. Control cultures were obtained two weeks after the completion of therapy, and follow-up was continued for one year. The overall clinical and microbiologic cure rate in the study group was 72% (95/125). The rate of relapse was not influenced by the treatment of Candida colonization of the female intestinal tract. The recurrence rate after treatment in the couples in which the man harbored yeast (oral cavity, penile coronal sulcus, seminal fluid) was lower (15.8% vs. 44.8%, P = .0019) than that recorded in the couples without sexual partner involvement. The identification and treatment of the male sexual partner's Candida colonization seems important in the prevention of recurrent vulvovaginitis. PMID- 1593560 TI - Prenatal ultrasonographic fetal iliac bone measurement. Correlation with gestational age. AB - The variety of circumstances under which ultrasound examinations are performed makes fetal iliac bone measurement an important indicator of gestational age. We studied 322 well-dated pregnancies from 13 to 40 weeks' gestation with sonogram measurements of the fetal iliac bone in order to examine the relationship between gestational age and bone length. The results indicate a linear relationship, as described by the equation iliac length = -0.376 + (0.0887) (gestational age). The fit of the data to a straight line was quite close (R2 = .877, P = .0001). The data were used to obtain a nomogram for growth of the fetal iliac bone. PMID- 1593561 TI - Hygroscopic cervical dilators and prostaglandin E2 gel for preinduction cervical ripening. A randomized, prospective comparison. AB - A randomized, prospective study compared the safety and efficacy of hygroscopic cervical dilators (36 patients) with intracervical prostaglandin E2 (PGE2) gel (38 patients) in preinduction cervical ripening. Maternal age, gestational age and parity were similar in both groups. Both groups had similar cervical Bishop scores upon admission. The change in the cervical score was 3.0 +/- 0.3 (mean +/- SEM) in the dilator group and 2.8 +/- 0.4 in the PGE2 group (P = .7). The mean length of time from amniotomy to delivery was similar in both groups (10.1 +/- 1.0 and 10.3 +/- 1.3 hours, respectively) (P = .9). The proportions of patients in each arm of the study undergoing cesarean section were similar. Eight cesarean sections (21.0%) were performed in the PGE2 group; seven (19.4%) were performed in the dilator group (P = .9). Maternal morbidity, five-minute Apgar scores and admissions to the neonatal intensive care unit were similar in the two groups. Because patients were required to stay in the labor-and-delivery unit for four to six hours of fetal monitoring after PGE2 application, the costs were higher in that group. The dilators and PGE2 gel appear comparable in efficacy as preinduction cervical ripening agents. The need to monitor patients receiving PGE2 gel, however, appears to favor the choice of the dilators from a cost and convenience perspective. PMID- 1593562 TI - Prenatal diagnosis of triploidy. A case report. AB - Fetal triploidy can be suspected but not diagnosed based on ultrasonographic findings. A patient was diagnosed with fetal triploidy in the second trimester. PMID- 1593563 TI - Expectant management of focal nodular hyperplasia during pregnancy. A case report. AB - A patient with unresectable focal nodular hyperplasia of the liver completed an uncomplicated pregnancy. Although there is a risk of hepatic rupture during pregnancy, expectant management may be an option for some cases of focal nodular hyperplasia. PMID- 1593564 TI - Herpes simplex infection associated with short-term use of a fetal scalp electrode. A case report. AB - A case of localized neonatal herpes simplex virus (HSV) infection involved a prior fetal scalp electrode site. Rupture of the fetal membranes, placement of the fetal scalp electrode and delivery occurred within 30 minutes. The mother had no previous history of genital lesions, and no herpetic lesions were noted at delivery. PMID- 1593565 TI - Left microtia in one monozygotic twin. A case report. AB - Monoamniotic twins are rare, with a double survival rate of only 40%. Congenital anomalies, while more common among twins in general, are particularly common in monoamniotic twins, with the increase principally the result of structural defects. Discordant phenotypes have been reported, but a malformation of the external ear in one twin has not. In a case of double survival of monoamniotic twins, one had left microtia and a single umbilical artery. PMID- 1593566 TI - Peripheral pulmonary artery stenosis in pregnancy. A report of two cases. AB - Peripheral pulmonary artery stenosis is a rare congenital anomaly often associated with the maternal rubella syndrome. Two patients with the disorder underwent four successful pregnancies. PMID- 1593567 TI - The clinical syndrome associated with antiphospholipid antibodies. PMID- 1593568 TI - The catastrophic antiphospholipid syndrome. PMID- 1593569 TI - Depressed adjuvant arthritis in chronically Trypanosoma cruzi infected rats: reversal by cyclophosphamide. AB - Chronically Trypanosoma cruzi infected "I" rats and syngeneic naive recipients, transferred with a T cell enriched spleen cell population from infected donors, develop an attenuated arthritis when challenged with complete Freund's adjuvant. We report that cyclophosphamide, 40 mg/kg body weight, given 48 h before induction, was able to reestablish or exacerbate adjuvant arthritis in infected and control rats, respectively. Although the T cell enriched spleen cells from infected donors continued to down regulate adjuvant arthritis in syngeneic recipients given cyclophosphamide 48 h before cell transfer, treatment of infected donors with cyclophosphamide, 48 h before cell collection, prevented these cells from exerting such effect when transferred to healthy recipients receiving no cyclophosphamide. It is suggested that cyclophosphamide may primarily affect a suppressor cell population, present in the infected host, with regulatory activity on adjuvant arthritis. PMID- 1593570 TI - Inhibitors of interleukin 1 activity in synovial fluids and in cultured synovial fluid mononuclear cells. AB - Measurement of interleukin 1 (IL-1) in synovial fluids (SF) yielded variable results and implied the presence of an inhibitory activity. As peripheral blood monocytes produce an IL-1 receptor antagonist (IL-1ra), we investigated whether SF mononuclear cells (SFMC) also secreted such inhibitory activity. MC isolated from inflammatory SF produced, in addition to variable levels of IL-1, a specific IL-1 inhibitor of approximately 23 kDa which blocked both IL-1 biological activity and binding to its receptor. Western blot, using a polyclonal antibody to rhIL-1ra, indicated that SFMC secreted material that shared immunological crossreactivity with the cloned IL-1ra. IL-1 inhibitory activity was also detected in SF but not formally demonstrated to be related to IL-1ra. In conclusion, SFMC could produce IL-1ra and an imbalance between IL-1 and its specific antagonist may be relevant to the severity of joint destruction. PMID- 1593571 TI - Cytokines and soluble interleukin 2 receptors in rheumatoid arthritis. AB - Cytokines (IL-1 alpha and IL-2) and soluble interleukin 2 receptors (sIL-2r) were evaluated in patients with rheumatoid arthritis (RA) and controls. In RA, serum sIL-2r and IL-1 alpha were increased, and sIL-2r were significantly higher in synovial fluid than in serum. Serum levels of sIL-1r but not IL-1 alpha were increased in patients with acute infections, suggesting additional discriminatory specificity for IL-1 alpha. Both tender and swollen joint scores were higher for patients with RA with serum sIL-2r levels greater than or equal to 700 U/ml. Quantitation of immune mediators may be useful in the clinical assessment of RA in addition to their implication regarding the pathogenesis of the disease. PMID- 1593572 TI - Lactate dehydrogenase activity and its isoenzymes in serum and synovial fluid of patients with rheumatoid arthritis and osteoarthritis. AB - By determining the total activity of total lactate dehydrogenase (LDH-T) and its isoenzymes in serum and synovial fluid (SF) of patients with rheumatoid arthritis (RA) and osteo-arthritis (OA) we demonstrated in RA serum increased (p less than 0.02) activity of hepatic LDH (LDH-H) and a shift of the LDH isoenzymatic profile towards the M forms; in rheumatoid SF increased (p less than 0.001) activity of the total LDH-T and LDH-H which makes possible the use of these markers of inflammation in assessing RA activity. Values for LDH-T and LDH-H of 400-700 U/l and 300-500 U/l, respectively, correspond to moderate disease activity, while values exceeding 750 U/l and 550 U/l, respectively, correspond to high RA activity. The anaerobic isoenzymatic distribution of LDH in rheumatoid SF results in a significant (p less than 0.001) decrease in LDH1 and LDH2 and an increase (p less than 0.001) in LDH4 and LDH5. PMID- 1593573 TI - Cyclosporine nephrotoxicity in rheumatoid arthritis: no effect of short term misoprostol treatment. AB - We assessed the effect of the prostaglandin E1 analog misoprostol on cyclosporine nephrotoxicity in patients with rheumatoid arthritis (RA). Thirteen patients with RA were given cyclosporine with misoprostol tablets, 800 micrograms/day for one week in a randomized, double blind, placebo controlled crossover trial. All had cyclosporine nephrotoxicity, documented by an increase in serum creatinine of at least 15% over the values before the start of cyclosporine treatment. Mean glomerular filtration rate (GFR) (single shot 51Cr-EDTA plasma clearance) at baseline was 77.3 ml/min (SD, 22.0). After misoprostol, it was 80.0 ml/min (SD, 18.9); after placebo, 79.1 ml/min (SD, 20.0). None of these changes were statistically significant. Serum creatinine levels and whole blood cyclosporine levels were also unchanged. Power to detect at least a 5 ml/min rise in GFR was 0.92. Short term misoprostol treatment does not improve the GFR of patients with RA on cyclosporine. PMID- 1593574 TI - A comparison of tenoxicam and piroxicam in the treatment of rheumatoid arthritis. AB - Tenoxicam 20 mg OD was compared with piroxicam 20 mg OD for patients with rheumatoid arthritis (RA). One hundred and two patients from 5 centers were enrolled: 51 in the tenoxicam group and 51 in the piroxicam group. Evaluation of the primary efficacy variables demonstrated no difference in efficacy between treatment groups. The overall incidence of adverse clinical/laboratory experiences was similar between treatment groups. Six patients discontinued the study because of gastrointestinal intolerance, 3 from each treatment group. Our study demonstrates that tenoxicam 20 mg OD and piroxicam 20 mg OD have similar efficacy and safety in patients with active RA. PMID- 1593575 TI - Generic versus disease specific health status measures: comparing the sickness impact profile and the arthritis impact measurement scales. AB - Health services researchers frequently must choose between a generic health status measure, such as the Sickness Impact Profile (SIP) and a disease specific health status measure, such as the Arthritis Impact Measurement Scales (AIMS). In a longitudinal study of patients with knee or hip osteoarthritis, we examined the extent to which these 2 measures provide similar information. We found the SIP and AIMS to be significantly (p less than 0.001) correlated for physical (0.75 0.76) and total health (0.70-0.73). Correlations for psychological health were statistically significant, albeit modest (0.37-0.40). We conclude that, for most dimensions, investigators will obtain similar information using either well validated instrument. PMID- 1593576 TI - Experience with 19-nortestosterone in the therapy of systemic lupus erythematosus: worsened disease after treatment with 19-nortestosterone in men and lack of improvement in women. AB - Three men and 4 women with systemic lupus erythematosus (SLE) received 100 mg of 19-nortestosterone decanoate in weekly intramuscular injections over a period of 3 to 24 months. During therapy in the men plasma luteotrophic hormone and free testosterone levels decreased while estrogen levels increased. Anti-DNA antibodies also increased for unknown reasons. Serological changes in two men coincided with an overall increase in the clinical activity of SLE and the appearance of new onset Raynaud's phenomenon and pleuropericardial disease. In contrast, women treated with 19-nortestosterone showed clinical stability despite the persistence of high titer antibodies to DNA, and were able to continue therapy for as long as 16 months in one case. These data indicate that men and women with SLE respond differently to synthetic androgen therapy. Additionally, dissociation of clinical signs and symptoms from serological variables seems possible. PMID- 1593577 TI - Lupus anticoagulant: correlation with magnetic resonance imaging of brain lesions. AB - Brain magnetic resonance imaging (MRI) was performed in 21 patients with systemic lupus erythematosus (SLE) with and without lupus anticoagulant (LAC), one lupus like patient and 5 patients with primary antiphospholipid antibody syndrome. Thirteen patients had white matter focal brain lesions on MRI, 10 of whom had LAC (p = 0.03). We found no correlation between these lesions and neurologic manifestations, nor any clinical or serologic indices of activity of SLE. Our MRI lesions were similar to those described in multiple sclerosis and may indicate a similar pathologic process. PMID- 1593578 TI - Cognitive impairment in patients with systemic lupus erythematosus. AB - Seventy unselected patients with systemic lupus erythematosus (SLE) were studied to determine the prevalence of cognitive impairment and the association with other clinical variables. Twenty-five patients with rheumatoid arthritis (RA) and 23 healthy subjects were used as controls. All patients were evaluated with a battery of standardized neuropsychological tests to determine ability in 8 areas of cognitive function. Clinically overt neuropsychiatric (NP) SLE, cumulative disease manifestations and concurrent medications were documented. In patients with SLE, generalized disease activity was expressed using the SLE disease activity index. Cognitive impairment was identified in 15/70 (21%) patients with SLE, 1/25 (4%) patients with RA and in 1/23 (4%) healthy subjects (p = 0.042). The prevalence was higher in patients with active NP-SLE at the time of assessment (2/5, 40%) compared to patients with inactive NP-SLE (2/10, 20%) but was also increased in those patients who had never had known clinical NP-SLE (11/55, 20%). A history of serositis (p = 0.015), active SLE (p = 0.064) and corticosteroid use (p = 0.027) at the time of assessment were more common in patients with cognitive impairment. The results suggest that cognitive impairment is increased in patients with SLE. It may occur independently of clinically overt NP-SLE and is more common in patients with active disease who are receiving corticosteroids. PMID- 1593579 TI - Central nervous system angiography: safety and predictors of a positive result in 125 consecutive patients evaluated for possible vasculitis. AB - To determine the complication rate of cerebral angiography and to identify variables associated with angiograms positive for vasculitis, we retrospectively evaluated 125 consecutive patients who had angiography because of possible central nervous system (CNS) vasculitis. Sixteen of 125 (12.8%) had angiograms positive for CNS vasculitis. Fourteen (11.5%) experienced a transient and 1 (0.8%) had a persistent neurologic deficit due to angiography. The complication rates between patients who were angiogram positive and angiogram negative did not differ (p greater than 0.05). Two clinical variables were significant risk factors for having an angiogram positive for CNS vasculitis: a preexisting rheumatic disease diagnosis (relative odds 3.39, 95% CI 1.08-10.62, p less than 0.033) and an abnormal lumbar puncture (relative odds 5.50, 95% CI 1.13-26.64, p less than 0.031). We conclude that the risk of persistent neurologic complications from angiography is low in patients who have or are suspected of having CNS vasculitis. PMID- 1593580 TI - Is there any evidence for an association between ankylosing spondylitis and Borrelia burgdorferi infection? AB - The suggested relationship between Borrelia burgdorferi and seronegative spondyloarthropathies has been studied in 125 patients with ankylosing spondylitis (AS). IgG antibodies to Borrelia burgdorferi were present in 11 of 125 patients (8.8%) and in 25 of 125 controls (20%). No patient had clinical Lyme borreliosis. HLA-B27 status was known for 82 patients with AS. There was no difference between B27+ and B27 patients. This study provides no evidence that Borrelia burgdorferi is associated with AS. PMID- 1593581 TI - Frequency and specificity of antibodies that crossreact with Borrelia burgdorferi antigens. AB - The frequency and specificity of antibodies that bind antigens of Borrelia burgdorferi in sera from 200 individuals with no evidence of past or current Lyme disease was determined. Sera were tested for both IgG and IgM antibodies to B. burgdorferi by Western blotting. The non-Lyme serum group included specimens from healthy adults and children in addition to specimens from patients with viral infection and rheumatic diseases. Crossreactive IgG antibodies occurred more frequently than IgM antibodies. The most frequently bound antigens corresponded to 41 kDa and 60 kDa Borrelial components. Of 200 specimens tested, 100 had antibodies that bound at least 1 antigen. Binding to multiple antigens occurred at much lower frequency. Our results indicate that determination of maximum crossreactivity of non-Lyme sera can be used to establish minimum criteria for determining a positive Western blot result for Lyme disease. PMID- 1593582 TI - Treatment with colchicine decreases white cell counts in synovial fluid of asymptomatic knees that contain monosodium urate crystals. AB - Synovial fluid (SF) samples, all containing monosodium urate crystals, obtained from 18 asymptomatic knees of 12 patients with gout, were serially analyzed before and one month after treatment with 1 mg/day of oral colchicine. Before treatment, the SF contained 612 [confidence limits (CL) = 282, 942] cells/mm3, while after treatment these values decreased to 274 (CL = 73, 471) cells/mm3 (p less than 0.005). In all cases, pretreatment cell counts were higher than the corresponding posttreatment values. The percentage of polymorphonuclear leukocytes also diminished from a pretreatment value of 13.0 (CL = 7, 19) to 4.5 (CL = 2, 7) after colchicine administration (p less than 0.005). These results strongly suggest the presence of baseline subclinical joint inflammation which is reduced by colchicine. The preventive effect of this drug on the occurrence of new attacks may relate to its effect in reducing the baseline inflammation of the asymptomatic joints. PMID- 1593583 TI - Crosscultural validation and reliability of 3 disease activity indices in systemic lupus erythematosus. AB - Rheumatologists from 4 countries, representing 8 rheumatology centers, tested 3 systemic lupus erythematosus (SLE) disease activity indices: the SLE Disease Activity Index (SLEDAI) from Toronto; the Systemic Lupus Activity Measure (SLAM) from Boston and the British Isles Lupus Assessment Group (BILAG) for their reproducibility and validity in the assessment of real patients. Seven patients representing a spectrum of disease manifestations and activity were each examined by 4 of 7 observers from all centers except Toronto, using a Youden square design. Each observer completed all 3 indices and a category rating scale for disease activity on each of the 4 patients seen. All 3 indices detected differences among patients. There was no detectable observer effect among the 7 observers with each of the 3 indices. There was a detectable order effect with the SLAM. The 3 indices are comparable and reproducible for evaluating disease activity in SLE. PMID- 1593584 TI - Repetitive use of pulse therapy with methylprednisolone and cyclophosphamide in addition to oral methotrexate in children with systemic juvenile rheumatoid arthritis--preliminary results of a longterm study. AB - Patients with systemic juvenile rheumatoid arthritis (JRA) are often poorly responsive to existing therapeutic modalities. We evaluated the effectiveness of pulse therapy consisting of methylprednisolone 30 mg/kg/day for 3 consecutive days combined with cyclophosphamide 0.4 g/m2 body surface area on the 3rd day, for 18 patients with definite systemic JRA, who were enrolled in an open trial of 12 months' duration. The children received pulse therapy every 3 months; oral methotrexate 10 mg/m2 was started after the first pulse. A rapid and clinically significant suppression of systemic and articular manifestations was seen in all patients. Significant decreases in laboratory indices of disease activity were also observed. Side effects were minor and reversible. The results of our preliminary trial support the development of a controlled study to evaluate the efficacy of pulse therapy in systemic JRA. PMID- 1593585 TI - Acute polyarthritis associated with birefringent lipid microspherules occurring in a patient with longstanding rheumatoid arthritis. AB - We describe a 52-year-old patient with longstanding rheumatoid arthritis (RA) who developed an acute polyarthritis of her hands and wrists. Synovial fluid analysis revealed the presence of intra and extracellular lipid microspherules with the typical appearance of Maltese crosses under polarized light microscopy. No other specific cause could be identified. This is the first description of an acute polyarthritis associated with lipid microspherules in RA. PMID- 1593586 TI - Primary antiphospholipid syndrome as a cause of intestinal infarction. AB - We describe 2 patients with primary antiphospholipid syndrome who developed intestinal infarction. In one it was preceded by intestinal angina and, upon surgery, was found to have a hypertrophied media of mesenteric arteries. In the other, the intestinal infarction developed abruptly and was found to be due to mesenteric thrombosis. Arterial occlusions in primary antiphospholipid syndrome may involve the mesenteric arteries causing intestinal infarction. Some lesions may be proliferative and others thrombotic. Their clinical course may reflect this. Intestinal infarction seems to be part of the clinical spectrum of primary antiphospholipid syndrome. PMID- 1593587 TI - Marked cerebrospinal fluid pleocytosis in systemic lupus erythematosus related cerebral ischemia. AB - Pleocytosis of the cerebrospinal fluid (CSF) may accompany central nervous system lesions that occur as a result of systemic lupus erythematosus (SLE); however, the number of CSF white blood cells is usually less than 50/mm3 and the predominant cell is the lymphocyte. A young woman with SLE had 2 acute episodes of hemorrhagic cerebral ischemia, each of which was associated with a neutrophilic CSF pleocytosis (white blood count 480-2250/mm3). This type of meningeal reaction may have been related to the proximity of the cerebral lesions to the ventricles, a phenomenon previously described in non SLE related cerebral infarcts. PMID- 1593588 TI - Subcutaneous pancreatic fat necrosis associated with acute arthritis. AB - Subcutaneous fat necrosis is a well described, rare sequela of acute pancreatitis. Uncommonly, arthritis is seen in association with these 2 disease processes. We report a case of fulminant pancreatitis presenting as an acute arthritis. Birefringent crystal-like structures led to initial diagnostic confusion with gout. PMID- 1593589 TI - Elbow synovitis related to an intraarticular osteoid osteoma of the humerus, with immunologic and histochemical studies. AB - An 18-year-old boy presented with elbow synovitis. Investigations disclosed an osteoid osteoma of the coronoid fossa confirmed by histology. The synovium appeared hypertrophic with histologic patterns resembling those seen in synovitis in rheumatoid arthritis. Immunohistochemistry showed lymphoid follicles composed of B and T cells. T lymphocytes were mainly of the CD4 phenotype, showing soluble interleukin 2 receptor (IL-2r) in places but were poorly positive for DR antigen. C3, C4, B factor and CH50 activity were decreased and interleukin 1 and soluble IL-2r were increased in synovial fluid. They were normal in peripheral blood except for a slight decrease in C4. These data suggest a local immunologic activation induced by osteoid osteoma, the mechanism of which remains hypothetic. Immunomodulating mediator diffusion from osteoid osteoma itself or as a secondary response to tumoral antigen release could be advocated. Whether such phenomena are specific to the epiphyseal location of osteoid osteoma needs clarification. PMID- 1593590 TI - Chronic idiopathic hyperphosphatasia. Report of a case treated with pamidronate and a review of the literature. AB - We describe the case of a 38-year-old woman with 24 years of progressive skeletal deformities. Radiologic survey showed evidence of generalized skeletal involvement. She presented with secondary osteoarthritis, and her hands showed Heberden's and Bouchard's nodes. Light microscopic examination showed many reversed lines in the trabeculae and increased bone resorption and bone forming areas. On electron microscopic study there were intranuclear inclusions in the osteoclasts. To our knowledge, she is the oldest patient described in the English literature, and the first treated with (3-amino-1-hydroxypropilidene)-1,1 biphosphonate (Pamidronate). She showed a decrease in serum alkaline phosphatase, urinary hydroxyproline. Clinical variables showed good response to medication. PMID- 1593591 TI - Naproxen induced ulcerative esophagitis. AB - Only 4% of upper gastrointestinal bleeding in the elderly is due to ulcerative esophagitis, and only rarely has nonsteroidal antiinflammatory drug (NSAID) related esophageal bleeding been reported. We describe a case of NSAID induced ulcerative esophagitis in an 87-year-old woman with documented esophageal dysmotility. PMID- 1593592 TI - Detection of opioid peptides in synovial tissues of patients with rheumatoid arthritis. PMID- 1593593 TI - Prophylaxis of NSAID gastropathy. PMID- 1593594 TI - Taplow reminiscences. PMID- 1593595 TI - Toxicity of antirheumatic medications in children with juvenile arthritis. AB - Using patient related examples, the toxicity of nonsteroidal antiinflammatory drugs and disease modifying antirheumatic drugs (DMARD) in juvenile arthritis (JA) is discussed. DMARD combinations are also reviewed. Gastrointestinal side effects are not emphasized. Rather, central nervous system, hepatic, and renal effects are discussed. Ibuprofen is safer than aspirin and has a generally good record. Although data is not excellent and often relies on open studies, hydroxychloroquine is probably the safest DMARD. Methotrexate appears safe, but studies in adults mandate some continued caution in its use in children. Combination DMARD therapy, while used, is dependent on largely open or anecdotal data in adults. The efficacy and toxicity of DMARD combinations are not well understood. PMID- 1593596 TI - Expressing our inner thoughts: how to organize and write a clinical research project grant application. AB - Securing funding for clinical research projects is becoming increasingly difficult. At present, scientific merit is an essential but not necessarily sufficient attribute of a successful research proposal. It is the premise of this article that each section of the application contributes important information to the reviewer and that carelessness or inattention to detail in any section may be a critical factor in the lack of success of an application. Each section of the standard NIH application is analyzed and suggestions are provided with regard to their organization and execution. PMID- 1593597 TI - Current concepts in immunosuppressive drug therapy of systemic lupus erythematosus. AB - The routine use of intravenous cyclophosphamide has led to advances in the preservation of renal function and quality of life for patients with systemic lupus erythematosus complicated by diffuse proliferative glomerulonephritis. Most patients receiving 3 years of intravenous cyclophosphamide according to a rigorous protocol experience longterm remission of their disease. However, in some the disease continues to progress or flares recurrently. Early intervention and combined immunosuppressive regimens modeled on protocols developed for the treatment of neoplastic disease appear to offer the greatest likelihood of attaining permanent remission for large numbers of patients. Pilot studies of these regimens are in progress. PMID- 1593598 TI - Newer functional outcome measurements in juvenile rheumatoid arthritis: a progress report. AB - Development of health status questionnaires for pediatric patients with rheumatic disease presents special challenges. At this time, several investigators are actively involved in development of health status instruments which have demonstrated reliability and internal validity. I review these instruments and outline future studies needed for these instruments. PMID- 1593599 TI - Immunity to cartilage proteoglycans. AB - Cartilage proteoglycans constitute a major component of articular cartilage. Humoral and cell-mediated immune responses to these proteoglycans have been observed in various human rheumatic diseases with varying incidences. The possibility of such autoimmune responses being of pathologic significance has been raised by the observation of the induction of arthritis in animals on immunization with proteoglycans. Immunization of BALB/c mice with human cartilage proteoglycan in adjuvant leads to the development of peripheral arthritis as well as spondylitis associated with immune reactivity to mouse cartilage proteoglycan. Pathogenic autoimmune reactions to cartilage proteoglycans may also be elicited by molecular mimicry with bacterial heat shock proteins. PMID- 1593600 TI - The emerging role of biologics in rheumatic disease. AB - Biologically based therapeutics may be classified as agents which (1) restore altered immunoregulatory, hematopoietic or other disease resistant functions, (2) modulate immunologic effector mechanisms (immunomodulators), or (3) upregulate or downregulate a specific cell function. There are several characteristics which differentiate biologic agents from more traditional pharmaceutical drugs. Administered parenterally, they often generate systemic effects, and may be associated with a higher placebo response. Many are administered not at pharmacologic, but "industrial strength" doses. The specific desired effect may be obscured by cytokine and other immunoregulatory networks. A host immune response typically occurs with repetitive administration; this may alter the pharmacokinetics of the agent but not necessarily the biologic or clinical effects. The use of biologic markers, both disease specific and agent specific, may allow more efficient clinical development of these agents. A variety of biologic agents are in clinical trials for the treatment of autoimmune diseases. These include interferon gamma, the IL-1 receptor antagonist and monoclonal antibodies to the T cell surface antigens CD4 and CD7. Two immunotoxins, CD5 ricin A chain, and diphtheria AB toxin-IL-2 are undergoing evaluation in rheumatoid arthritis. Data regarding these agents will be reviewed. Issues specific to their use in pediatric clinical applications will be discussed. PMID- 1593601 TI - Working with diverse families: building culturally competent systems of health care delivery. AB - In the face of increasing heterogeneity among American families, it is imperative health care systems and professionals be culturally sensitive and competent. As we enter a new era of parent-professional collaboration, where services are family centered, community based and coordinated, grasping the richness, and complexity, of working with a pluralistic clientele is essential. Self-awareness regarding one's personal heritage, and the desire to know how clients view and accept Western health practices, are the beginnings of cultural competence. This article examines various strategies professionals can use to assure that such competent programs are a norm. PMID- 1593602 TI - Nutrition and pediatric rheumatic diseases. Hypothesis: cytokines modulate nutritional abnormalities in rheumatic diseases. AB - Growth abnormalities are common in pediatric rheumatic diseases. Studies suggest that effects of inflammation such as anorexia, and adipose and muscle tissue breakdown contribute to the nutritional and growth aberrations. The effects of the various cytokines produced during inflammation create a vicious cycle of anorexia and increased catabolism, and may be responsible for the nutritional deficits seen. In future, specific treatment with anticytokine monoclonal antibodies may block these effects, minimizing the nutritional consequences of inflammation. PMID- 1593603 TI - Osteoporosis as a pediatric disease: role of calcium and heredity. AB - Osteoporosis is characterized by a reduction in bone mass. This reduction may be determined during growth or acquired in later life. Since osteoporosis is easier to prevent than to treat, the goal is therefore to identify individuals who might be at high risk. We suggest that the identification of those individuals should start in childhood and adolescence. Calcium intake and skeletal modelling/turnover are the most important determinants of calcium balance during this age period. Adequate calcium supply should contribute to peak bone mass and therefore prevention of osteoporosis later in life. We indicate that genetic information from both parents plays an important role as well. PMID- 1593604 TI - Dismantling the pyramid. AB - The suggestion is heard, with increasing frequency, that the therapeutic pyramid be dismantled and that medical management be reordered to treat juvenile rheumatoid arthritis as early and as decisively as possible to induce prompt remission of disease, thereby preserving function and the quality of life. We scrutinize paradigms that guide our treatment strategies, review current practices, update data derived from those practices, and propose reassessment for treatment in the 1990s. PMID- 1593605 TI - The role of the MHC in autoimmunity: an overview. AB - The basis for MHC associations with autoimmune diseases is still unknown; however, recent progress in the study of the MHC, its gene products and their functions suggests a number of possible mechanisms. These paradigms are described and their applicability to particular autoimmune diseases is considered. PMID- 1593606 TI - Juvenile rheumatoid arthritis and HLA: report of the Park City III workshop. AB - The workshop held during the Park City Meeting was directed toward developing a consensus about HLA associations in juvenile rheumatoid arthritis (JRA). Most agreement was achieved in pauciarticular JRA where the strongest associations were with the HLA-DRB1 alleles as is also the case in IgM rheumatoid factor positive polyarticular disease. In addition, HLA-DP associations are being identified although roles for linked genes are still possible. The critical nucleotides among HLA genes are not known; however, disease specific mutations have not been shown. PMID- 1593607 TI - Radiological approaches to pediatric joint disease. AB - With the recent advances that have become available with imaging, we are able to gain considerable information about joint diseases. Although conventional radiography still plays a very important part in the diagnosis of joint disease, ultrasound, computed tomography, magnetic resonance imaging, and nuclear medicine studies have all enhanced our ability to evaluate joint disorders. Each of these modalities need not be used in every patient but when chosen carefully, can efficiently provide useful information both for diagnosis and management. These various modalities are also extremely useful to rule out the mimics of joint disease. Magnetic resonance has recently been shown to be useful in evaluation of dermatomyositis and of vasculitides in the brain. PMID- 1593608 TI - Intravenous immunoglobulin therapy: magic or black magic. AB - Intravenous immunoglobulin (IVIG) therapy has been used not only as replacement treatment for immunodeficiency, but also as treatment of autoimmune diseases, specifically Kawasaki disease, systemic juvenile arthritis and juvenile dermatomyositis. In Kawasaki disease, IVIG reduces the incidence of coronary artery abnormalities, as well as rapidly improving clinical and laboratory variables such as fever and rash, platelet count, white blood cell count and serum albumin. Furthermore, a single high dose of 2 g/kg is as effective as 400 mg/kg x 4 days. In systemic juvenile arthritis, followup of at least one year demonstrated that monthly treatment with IVIG resulted in improvement of systemic disease in 10/11 patients, allowed for cessation of prednisone treatment in 7/8 patients and significant improvement of arthritis in 8 patients. In juvenile dermatomyositis, we report 2 uncontrolled trials of IVIG treatment that resulted in significant clinical improvement and steroid-sparing. In contrast, IVIG treatment of systemic lupus erythematosus (SLE) resulted in improvement in 3 patients, but exacerbation or new onset of renal disease in 3 patients. Overall, our report demonstrates that IVIG has been effective both in a controlled trial in Kawasaki disease and in uncontrolled trials in systemic juvenile arthritis and juvenile dermatomyositis. We suggest that IVIG should be used cautiously in SLE. PMID- 1593609 TI - The role of infection in chronic arthritis. AB - The hypothesis that in arthritis an infectious agent functions at least as a triggering factor, if not a perpetuating one, has inspired decades of clinical investigation. Increasingly these studies are using more sophisticated tools of molecular biology which are applied in microbiology, immunology and immunogenetics. In the spondyloarthropathies these newer techniques are defining the molecular bases for the interplay of microbial antigen and the MHC antigens. The clues to provocative antigens are still elusive, although the class II MHC susceptibility is becoming clarified. Both viral and mycobacterial antigens are being examined in rheumatoid arthritis, but definitive answers are still lacking. PMID- 1593610 TI - Ionic effects on bumetanide binding to the activated Na/K/2Cl cotransporter: selectivity and kinetic properties of ion binding sites. AB - The loop diuretic bumetanide binds specifically to the Na/K/2Cl cotransporter of many cell types including duck erythrocytes. Membranes isolated from these erythrocytes retain the ability to bind bumetanide when cells are exposed to cotransport-activity stimuli prior to membrane isolation. An extensive study of the effects of ions on specific [3H]bumetanide binding to such membranes is presented here and compared to the activity of these ions in supporting transport function in intact cells. Both Na+ and K+ enhanced bumetanide binding in a saturable manner consistent with a single-site interaction. The Km for each ion was dependent on the concentration of the other cation suggesting heterotropic cooperative interactions between the Na+ and K+ binding sites. Na+ and K+ were partially replaceable, with the selectivity of the Na+ site being Na+ greater than Li+ greater than NH4+; N-methyl-D-glucamine+, choline+ and tetramethylammonium+ also supported a small amount of specific binding when substituted for Na+. The selectivity of the K+ site was K+ approximately Rb+ greater than NH4+ greater than Cs+; N-methyl-D-glucamine+, choline+ and tetramethylammonium+ were inactive at this site. The results of transport experiments revealed a slightly different pattern. Li+ could partially substitute for Na+ in supporting cotransport, but other monovalent cations were completely inactive. The order of potency at the K+ site was NH4+ greater than K+ approximately Rb+ greater than Cs+ much greater than other monovalent cations. The effect of Cl- on bumetanide binding was biphasic, being stimulatory at low [Cl-] but inhibitory at high [Cl-]. As this implies the existence of two Cl- binding sites (termed ClH and ClL for the "high-" and "low-" affinity sites, respectively) each phase was examined individually. Cl- binding to ClH could be described by a rectangular hyperbola with a Km of 2.5 mM, while kinetic analysis of the inhibition of bumetanide binding at high [Cl-] revealed that it was of a noncompetitive type (Ki = 112.9 mM). The selectivity of anion binding to the two sites was distinct. ClH was highly selective with Cl- greater than SCN- greater than Br-; F-, NO3-, ClO4-, MeSO4-, gluconate- and SO4(2-) were inactive. The efficacy of anion inhibition of binding to ClL was ClO4- greater than I- greater than SCN- greater than NO3- greater than Cl-; F-, MeSO4-, gluconate-, and SO4(2-) were inactive. Thus, ClH is much more selective than ClL and largely accounts for the specificity of the system with respect to anion transport.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593611 TI - Calcium-activated chloride conductance of lactotrophs: comparison of activation in normal and tumoral cells during thyrotropin-releasing-hormone stimulation. AB - We studied a chloride (Cl-) conductance activated by calcium (Ca2+) in normal rat lactotrophs and compared its activation during TRH stimulation in normal rat lactotrophs and in GH3 tumoral lactosomatotrophs cells, using the whole-cell configuration of the patch-clamp technique. The Cl- specificity of the conductance was assessed by manipulation of internal and external Cl- concentrations. The reversal potentials were in agreement with those predicted by the Nernst equation. Ca2+ ionophore A23187 and membrane depolarizations activated the Cl- conductance. However, a feedback effect of Cl- gradient modifications on Ca2+ movements was also observed in normal lactotrophs. In the latter, TRH (100 nM) mobilization of intracellular Ca2+ activated this Cl- conductance together with the potassium (K+) conductance when both ions were present in the intracellular medium (IM) or alone when K+ was absent. Chloride conductance was not activated in the GH3 cells, where mobilization of intracellular Ca2+ by TRH (100 nM) activated only Ca2(+)-dependent K+ conductance. It seems likely that the activation of Cl- conductance in these two different cell types involves different mechanisms. PMID- 1593612 TI - A choline transporter in renal brush-border membrane vesicles: energetics and structural specificity. AB - Choline is a quaternary ammonium compound that is normally reabsorbed by the renal proximal tubule, despite its acknowledged role as a substrate for the renal organic cation (OC) secretory pathway. The basis for choline reabsorption was examined in studies of transport in rabbit renal brush-border membrane vesicles (BBMV). Although an outwardly directed H+ gradient (pH 6.0in: 7.5out) stimulated uptake of tetraethylammonium (TEA), a model substrate of the OC/H+ exchanger in renal BBMV, it had no effect on uptake of 1 microM choline. A 5 mM trans concentration gradient of choline did, however, drive countertransport of both TEA and choline, although trans TEA had no effect on choline accumulation in BBMV. A 20 mM concentration of unlabeled choline blocked uptake of both choline and TEA by greater than 85%, whereas 20 mM TEA blocked only TEA uptake. The kinetics of choline uptake into vesicles preloaded with 1 mM unlabeled choline appeared to involve two, saturable transport processes, one of high affinity for choline (Kt of 97 microM) and a second of low affinity (Kt of approximately 10 mM), the latter presumably reflecting a weak interaction of choline with the OC/H+ exchanger. An inside-negative electrical PD stimulated the rate of uptake and supported the transient concentrative accumulation of choline in BBMV. The high affinity transporter showed a marked specificity for choline and closely related analogues. A model of the molecular determinants of substrate-transporter interaction is described. We conclude that the electrogenic high affinity pathway plays a central role in renal reabsorption of choline. PMID- 1593613 TI - Kinetics of DIDS inhibition of swelling-activated K-Cl cotransport in low K sheep erythrocytes. AB - The inhibitory effect of various stilbene disulfonates was examined on the swelling-activated Cl-dependent K transport (K-Cl cotransport) in low K sheep erythrocytes. Both diisothiocyanatostilbenes H2DIDS and DIDS were found to be potent inhibitors. The DIDS concentration yielding 50% inhibition (IC50) of KCl cotransport was 60 microM in the absence of external K and 3 microM at physiological K concentration. Other stilbene derivatives, such as SITS (4 acetamido-4' isothiocyanatostilbene-2,2'-disulfonic acid), were only effective in the presence of external K, whereas DNDS (4,4'-dinitrostilbene-2,2'-disulfonic acid) and ISA (4-sulfophenyl isothiocyanate) had only slight effects at a concentration of 1 mM. The augmenting effect of external K is due to a second K site, distinguishable from the K transport site by its much higher affinity. No inhibition occurred in the absence of external Cl, whether or not external Rb(K) was present. Additionally, DIDS inhibited K-Cl cotransport activated by thiol alkylation with N-ethylmaleimide (NEM) as well as by Mg depletion in the presence of A23187 and a chelator. We conclude that allosteric sites affect the stilbene binding. When these sites are saturated, changes in external K or Cl concentration do not affect the affinity for DIDS (noncompetitive inhibition). PMID- 1593615 TI - Effects of osmotic stress on mast cell vesicles of the beige mouse. AB - The large size of the vesicles of beige mouse peritoneal mast cells (4 microns in diameter) facilitated the direct observation of the individual osmotic behavior of vesicles. The vesicle diameter increased as much as 73% when intact cells were perfused with a 10 mM pH buffer solution; the swelling of the vesicle membranes exceeded that of the insoluble vesicle gel matrix, which resulted in the formation of a clear space between the optically dense gel matrix and the vesicle membrane. Hypertonic solutions shrank intact vesicles of lysed cells in a nonideal manner, suggesting a limit to the compressibility of the gel matrix. The nonideality at high osmotic strengths can be adequately explained as the consequence of an excluded volume and/or a three-dimensional gel-matrix spring. The observed osmotic activity of the vesicles implies that the great majority of the histamine known to be present is reversibly bound to the gel matrix. This binding allows vesicles to store a large quantity of transmitter without doing osmotic work. The large size of the vesicles also facilitated the measurement of the kinetics of release as a collection of individual fusion events. Capacitance measurements in beige mast cells revealed little difference in the kinetics of release in hypotonic, isotonic, and hypertonic solutions, thus eliminating certain classes of models based on the osmotic theory of exocytosis for mast cells. PMID- 1593614 TI - Characterization of K+ currents in rat malignant lymphocytes (Nb2 cells). AB - Membrane K+ currents of malignant lymphocytes (Nb2 cells) were studied with the whole-cell patch-clamp method. Upon depolarization, K+ currents activate with a delay and follow a sigmoid time course, resembling other delayed rectifier K+ currents present in nerve and muscle cells. The activation time constant of these currents is voltage dependent, increasing from 1 msec at +90 mV to approximately 37 msec at -30 mV. The fractional number of open channels has a sigmoid voltage dependence with a midpoint near -25 mV. Deactivation of K+ currents in Nb2 cells is voltage dependent and follows a simple exponential time course. Time constant of this process increases from 5 msec at -115 mV to almost 80 msec at -40 mV. The relative permeability of K+ channels to different monovalent cations follows the sequence: K+ (1) greater than Rb+ (0.75) greater than NH4+ (0.11) greater than Cs+ (0.07) greater than Na+ (0.05). Inactivation of K+ currents is a biexponential process with time constants of approximately 600 and 7,000 msec. Inactivation of K+ currents in Nb2 cells is not a voltage-dependent process. The steady-state inactivation curve of K+ currents has a midpoint near -40 mV. Following a 500-msec voltage pulse, inactivation of K+ currents recovers with a simple exponential process with a time constant of 9 sec. Short duration (approximately 50 msec) voltage-clamp pulses do not induce significant inactivation of these currents. K+ currents in malignant lymphocytes do not display the phenomenon of cumulative inactivation as described for other delayed rectifier-type K+ channels. Application of a train of voltage pulses to positive potentials at different frequencies induces a moderate decrease in peak outward currents. The use of substances (N-bromoacetamide, trypsin, chloramine-T, and papain) that remove the inactivation of Na+ and K+ currents in other cells are not effective in removing the inactivation of K+ currents present in this lymphoma cell line. Significant differences were found between the characteristics of K+ currents in this malignant cell line and those present in normal lymphocytes. Possible physiological implications for these differences and for the role of K+ currents in the proliferation of normal and malignant lymphocytes are discussed. PMID- 1593616 TI - Inwardly rectifying potassium current in rabbit osteoclasts: a whole-cell and single-channel study. AB - Ionic conductances of rabbit osteoclasts were investigated using both whole-cell and cell-attached configurations of the patch-clamp recording technique. The predominant conductance found in these cells was an inwardly rectifying K+ conductance. Whole-cell currents showed an N-shaped current-voltage (I-V) relation with inward current activated at potentials negative to EK. When external K+ was varied, I-V curves shifted 53 mV/10-fold change in [K+]out, as predicted for a K(+)-selective channel. Inward current was blocked by Ba2+ and showed a time-dependent decline at negative potentials, which was reduced in Na(+)-free external solution. Inward single-channel currents were recorded in the cell-attached configuration. Single-channel currents were identified as inward rectifier K+ channels based on the following observations: (i) Unitary I-V relations rectified, with only inward current resolved. (ii) Unitary conductance (gamma) was 31 pS when recorded in the cell-attached configuration with 140 mM K+ in the pipette and was found to be dependent on [K+]. (iii) Addition of Ba2+ to the pipette solution abolished single-channel events. We conclude that rabbit osteoclasts possess inwardly rectifying K+ channels which give rise to the inward current recorded at negative potentials in the whole-cell configuration. This inwardly rectifying K+ current may be responsible for setting the resting membrane potential and for dissipating electrical potential differences which arise from electrogenic transport of protons across the osteoclast ruffled border. PMID- 1593617 TI - Membrane potential modulates divalent cation entry in rat parotid acini. AB - This study examines the effect of membrane potential on divalent cation entry in dispersed parotid acini following stimulation by the muscarinic agonist, carbachol, and during refill of the agonist-sensitive internal Ca2+ pool. Depolarizing conditions (addition of gramicidin to cells in Na(+)-containing medium or incubation of cells in medium with elevated [K+]) prevent carbachol stimulated hyperpolarization of acini and also inhibit carbachol activation of Ca2+ and Mn2+ entry into these cells. Conditions promoting hyperpolarization (cells in medium with Na+ or with N-methyl-D-glucamine instead of Na+) enhance carbachol stimulation of divalent cation entry. Intracellular Ca2+ release (initial increase in [Ca2+]i) does not appear to be affected by these manipulations. Mn2+ entry into resting and internal Ca2+ pool-depleted cells (10 min carbachol stimulation in a Ca(2+)-free medium) is similarly affected by membrane potential modulations, and refill of the internal pool by Ca2+ is inhibited by depolarization. The inhibitory effects of depolarization on divalent cation entry can be overcome by increasing extracellular [Ca2+] or [Mn2+]. These data demonstrate that the modulation of Ca2+ entry into parotid acini by membrane potential is most likely due to effects on the electrochemical gradient (Em-ECa) for Ca2+ entry. PMID- 1593618 TI - Structural analysis of ternary complexes of Escherichia coli RNA polymerase. Individual complexes halted along different transcription units have distinct and unexpected biochemical properties. AB - Ternary complexes containing RNA polymerase, DNA and nascent RNA are intermediates in all RNA syntheses and are the targets of cellular factors that regulate RNA chain elongation and termination. Hence, elucidation of the structure and properties of these complexes is essential for understanding the catalytic and regulatory properties of the enzyme. We have described methods to prepare ternary complexes halted at defined positions along the DNA template, using specific dinucleotides to prime chain initiation along with limited subsets of the NTP substrates. Study of these static, halted complexes may provide information about the structure and properties of the transient elongation intermediates involved in transcription, although there is no necessary direct relationship between the two. Using specific halted complexes as precursors, we have walked the RNA polymerase along its template, producing defined ternary complexes at unique sites along two different transcription units. These complexes differ significantly from one another in many biochemical properties, in dramatic contrast to the properties expected from models that postulate a monotonous structure for elongation intermediates. These differences include variations in complex mobility during electrophoresis in non-denaturing polyacrylamide gels, in thermal stability and in stability to dissociation. Some halted complexes lose the ability to resume elongation when presented with the missing substrates. These "dead end" complexes must represent metastable structures in which elongation is blocked, and demonstrate clearly that not all halted complexes can be considered true intermediates in elongation. Other halted complexes rapidly cleave the nascent RNA seven nucleotides from the 3' terminus, in an unexpected and unusual biochemical reaction. These differences in properties among complexes bearing transcripts that differ by only one or a few nucleotides suggest that they have distinct structures. These differences must be due, at least in part, to differences in the template sequence and the length of the transcript. The results raise important questions as to the actual mechanism of transcription elongation, and suggest that it is a much more complex process than previously assumed. PMID- 1593619 TI - Structural analysis of ternary complexes of Escherichia coli RNA polymerase. Deoxyribonuclease I footprinting of defined complexes. AB - The structure and properties of ternary complexes of RNA polymerase are of central importance in understanding the mechanisms of transcriptional elongation and termination, and the regulation of these primary steps in gene expression. However, there has been no systematic study of the structure and properties of such complexes along a single transcription unit. Recently, we have described the isolation of a collection of halted ternary complexes of Escherichia coli RNA polymerase bearing transcripts from 11 to 35 nucleotides in length along two different transcription units (accompanying paper). Here, we report structural studies of these complexes using DNase I footprinting. Surprisingly, nearly all of the different ternary complexes have distinctly different footprints along the two DNA strands, and the position of the footprint relative to the 3' end of the transcript also varies for most complexes. Halted complexes bearing transcripts of comparable size do not have identical footprints; hence, DNA sequence as well as transcript length plays a role in determining the size and position of the footprint. These differences in structure are consistent with our earlier findings that ternary complexes can differ considerably in stability and gel mobility. The downstream boundary of the RNA polymerase in ternary complexes does not move forward regularly as successive nucleotide residues are added to the RNA chain. In contrast, the upstream boundary moves forward more or less in concert with the movement of the 3' terminus of the transcript. These factors lead to a general compression of the overall footprint as transcription proceeds, together with a steady movement of the 3' terminus of the RNA toward the downstream boundary of the polymerase. Ultimately, after the length of the RNA transcript has increased from eight to ten nucleotides, the downstream boundary of the complex is found to move downstream along the DNA, suggesting a translocation event. We suggest that RNA chain elongation, like RNA chain initiation, may involve a saltatory process in which net translocation of the complex along the DNA occurs only after addition of a number of ribonucleotides to the RNA chain. PMID- 1593620 TI - Central domain of the positive control protein NifA and its role in transcriptional activation. AB - The positive control protein NifA of Klebsiella pneumoniae activates transcription by RNA polymerase containing sigma 54 by catalysing open promoter complex formation. We show that the integrity of the putative ATP-binding pocket in the central domain of NifA is necessary for the positive control function of NifA, but is not required for DNA-binding or recognition of NifA by NifL. The inactive mutant NifA proteins are trans dominant to wild-type NifA and are unable to catalyse formation of open promoter complexes irrespective of whether a closed promoter complex at the nifH promoter has preformed. Formation of the closed complex results in a DNA structural distortion adjacent to the DNA region melted in the open promoter complex. This distortion lies at the leading edge of the E sigma 54 footprint. Although unable to catalyse open complex formation, some mutant NifAs altered the chemical reactivity of the distorted base-pair indicating that they retain the ability to recognize the closed promoter complex. The activation phenotype of partially active NifA molecules was sensitive to promoter sequences known to influence closed complex formation, indicating differences in (1) the susceptibility of the closed complexes towards activation and (2) their requirements for NifA during activation. PMID- 1593621 TI - Control of adenovirus major late gene expression at multiple levels. AB - Most late adenovirus (Ad) proteins are translated from mRNAs originating from the so-called major late transcription unit (MLTU). These mRNAs are grouped into five families (designated L1 to L5), where each family consists of mRNAs that have co terminal 3' ends. We have used mutant and wild-type Ad infections to characterize levels at which major late gene expression is regulated. Our results suggest the existence of a novel intermediate stage during a lytic infection where mRNAs from regions L1 and L4 are selectively overexpressed compared to the L2, L3, and L5 mRNAs. Our data suggest that this RNA phenotype reflects the activity of the MLTU at a transient stage immediately following initiation of viral DNA replication. Early during an Ad infection only mRNA from region L1 accumulate. To efficiently accumulate mRNA from regions L1 and L5 both viral DNA replication and late protein synthesis were required. To allow for only viral DNA replication resulted in an extensive premature transcription termination and a preferential mRNA accumulation from regions L1 and L4. The surprising production of L4 mRNA under these conditions was not due to the activation of a novel r-strand promoter located in the vicinity of region L4 or due to a control at the level of RNA transport or stability. Instead our results indicate that in the absence of efficient late protein synthesis 3' end formation occurs preferentially at the L1 and L4 poly(A) addition sites. PMID- 1593622 TI - Characterization of the F plasmid mating aggregation gene traN and of a new F transfer region locus trbE. AB - The product of the F plasmid transfer gene, traN, is thought to be required for the formation of stable mating aggregates during F-directed conjugation. By testing chimeric plasmids that express F transfer region segments for complementation of F lac traN mutant transfer, we mapped traN to the F transfer region between trbC and traF. Both protein and DNA sequence analysis determined the traN product to be a large, 66,000-Mr, polypeptide that undergoes signal sequence processing. The mature polypeptide was associated with outer membrane protein fractions, and a protease accessivity test confirmed that at least one portion of TraN is exposed on the cell surface. Our DNA sequence analysis also revealed that another gene, trbE, is located between traN and traF. The product of trbE was identified and shown to be a small, integral, inner membrane protein. The mating efficiency and pilus-specific phage susceptibility of a trbE::kan insertion mutant suggested that trbE is not essential for F transfer from Escherichia coli K-12 under standard mating conditions. PMID- 1593623 TI - Mutagenesis of a conserved region of the gene encoding the FLP recombinase of Saccharomyces cerevisiae. A role for arginine 191 in binding and ligation. AB - The FLP recombinase from the 2 microns plasmid of Saccharomyces cerevisiae contains a region from amino acid 185 to 203 that is conserved among several FLP like proteins from different yeasts. Using site-directed mutagenesis, we have made mutations in this region of the FLP gene. Five of twelve mutations in the region yielded proteins that were unable to bind to the FLP recombination target (FRT) site. A change of arginine at position 191 to lysine resulted in a protein (FLP-R191K) that could bind to the FRT site but could not catalyze recombination. This mutant protein accumulated as a stable protein-DNA complex in which one of the two bound FLP proteins was covalently attached to the DNA. FLP-R191K was defective in strand exchange and ligation and was unable to promote protein protein interaction with half-FRT sites. The conservation of three residues in all members of the integrase family of site-specific recombinases (His305, Arg308, Tyr343 in FLP) implies a common mechanism of recombination. The conservation of arginine 191 and the properties of the FLP-R191K mutant protein suggest that this arginine also plays an important role in the mechanism of FLP mediated site-specific recombination. PMID- 1593624 TI - Balbiani ring 1 gene in Chironomus tentans. Sequence organization and dynamics of a coding minisatellite. AB - Balbiani ring (BR) genes in diptera encode large secretory proteins and are classical model systems for studies of gene expression. In Chironomus tentans, four closely related BR genes, BR 1, BR 2.1, BR 2.2 and BR 6 form a gene family. The BR genes have been partially characterized and are known to contain long arrays of tandemly arranged repeat units with an hierarchical repeat organization. Here, we report the sequence organization of the complete transcribed part of the BR 1 gene in C. tentans. The gene contains five exons and four introns. Three of the introns are located at the 5' end and the fourth at the 3' end of the gene. Exon 4 is approximately 35,000 bases long and is built completely from tandemly organized repeats. We show that this long repeat block contains two types of related repeat units, beta and gamma. Each type forms a large uninterrupted array, a 5' beta array and a 3' gamma array with a sharp border between them. In the hierarchical repeat structure in each repeat array, all repeats are virtually identical at one level of repetition, but shown differences at the next level. The whole repeat block in the BR 1 gene fluctuates in size between different alleles, but not by more than 10%. In contrast, within the block, the beta and gamma arrays vary in length between 8000 and 29,000 bases in an inverse fashion, together keeping the overall length requirement. We propose that the length of exon 4 is conserved by selection of cross-over products of a given length, and that the internal hierarchical sequence organization in the BR 1 gene is a consequence of the combined action of several different sequence turnover mechanisms, all dependent on the unequal pairing of homologous sequences at different, competing levels of repetition. PMID- 1593625 TI - Predicting protein secondary structure using neural net and statistical methods. AB - A comparison of neural network methods and Bayesian statistical methods is presented for prediction of the secondary structure of proteins given their primary sequence. The Bayesian method makes the unphysical assumption that the probability of an amino acid occurring in each position in the protein is independent of the amino acids occurring elsewhere. However, we find the predictive accuracy of the Bayesian method to be only minimally less than the accuracy of the most sophisticated methods used to date. We present the relationship of neural network methods to Bayesian statistical methods and show that, in principle, neural methods offer considerable power, although apparently they are not particularly useful for this problem. In the process, we derive a neural formalism in which the output neurons directly represent the conditional probabilities of structure class. The probabilistic formalism allows introduction of a new objective function, the mutual information, which translates the notion of correlation as a measure of predictive accuracy into a useful training measure. Although a similar accuracy to other approaches (utilizing a mean-square error) is achieved using this new measure, the accuracy on the training set is significantly and tantalizingly higher, even though the number of adjustable parameters remains the same. The mutual information measure predicts a greater fraction of helix and sheet structures correctly than the mean-square error measure, at the expense of coil accuracy, precisely as it was designed to do. By combining the two objective functions, we obtain a marginally improved accuracy of 64.4%, with Matthews coefficients C alpha, C beta and Ccoil of 0.40, 0.32 and 0.42, respectively. However, since all methods to date perform only slightly better than the Bayes algorithm, which entails the drastic assumption of independence of amino acids, one is forced to conclude that little progress has been made on this problem, despite the application of a variety of sophisticated algorithms such as neural networks, and that further advances will require a better understanding of the relevant biophysics. PMID- 1593626 TI - Structure of a B-DNA decamer with a central T-A step: C-G-A-T-T-A-A-T-C-G. AB - The X-ray crystal structure analysis of the decamer C-G-A-T-T-A-A-T-C-G has been carried out to a resolution of 1.5 A. The crystals are space group P2(1)2(1)2(1), cell dimensions a = 38.60 A, b = 39.10 A, c = 33.07 A. The structure was solved by molecular replacement and refined with X-PLOR and NUCLSQ. The final R factor for a model with 404 DNA atoms, 108 water molecules and one magnesium hexahydrate cation is 15.7%. The double helix is essentially isostructural with C-G-A-T-C-G-A T-C-G, with closely similar local helix parameters. The structure of the T-T-A-A center differs from that found in C-G-C-G-T-T-A-A-C-G-C-G in that the minor groove in our decamer is wide at the central T-A step rather than narrow, and the twist angle of the T-A step is small (31.1 degrees) rather than large. Whereas the tetrad model provides a convenient framework for discussing local DNA helix structure, it cannot be the entire story. The articulated helix model of DNA structure proposes that certain sequence regions of DNA show preferential twisting or bending properties, whereas other regions are less capable of deformation, in a manner that may be useful in sequence recognition by drugs and protein. Further crystal structure analyses should help to delineate the precise nature of sequence-dependent articulation in the DNA double helix. PMID- 1593627 TI - Three-dimensional structures of bulge-containing DNA fragments. AB - The three-dimensional structure of a DNA tridecamer d(CGCAGAATTCGCG)2 containing bulged adenine bases was determined by single crystal X-ray diffraction methods, at 120 K, to 2.6 A resolution. The structure is a B-DNA type double helix with a single duplex in the asymmetric unit. One of the bulged adenine bases loops out from the double helix, while the other stacks in to it. This is in contrast to our preliminary finding, which indicated that both adenine bases were looped out. This revised model was confirmed by the use of a covalently bound heavy-atom derivative. The conformation of the looped-out bulge hardly disrupts base stacking interactions of the bases flanking it. This is achieved by the backbone making a "loop-the-loop" curve with the extra adenine flipping over with respect to the other nucleotides in the strand. The looped-out base intercalates into the stacked-in bulge site of a symmetrically related duplex. The looped-out and stacked-in bases form an A.A reversed Hoogsteen base-pair that stacks between the surrounding base-pairs, thus stabilizing both bulges. The double helix is frayed at one end with the two "melted" bases participating in intermolecular interactions. A related structure, of the same tridecamer, after soaking the crystals with proflavin, was determined to 3.2 A resolution. The main features of this B-DNA duplex are basically similar to the native tridecamer but differ in detail especially in the conformation of the bulged-out base. Accommodation of a large perturbation such as that described here with minimal disruption of the double helix shows both the flexibility and resiliency of the DNA molecule. PMID- 1593628 TI - Comparison of the solution conformations of human [Zn7]-metallothionein-2 and [Cd7]-metallothionein-2 using nuclear magnetic resonance spectroscopy. AB - The solution structure of native human [Zn7]-metallothionein-2 has been compared with the previously determined structure of human [Cd7]-metallothionein-2. The comparison was based on complete sequence-specific 1H nuclear magnetic resonance assignments for human [Zn7]-metallothionein-2 obtained using the sequential assignment method. The secondary structure was found to be very similar in the [Zn7]- and [Cd7]- forms of the protein. Only seven amide protons in [Zn7]- metallothionein-2 were found to have exchange rates lower than approximately 0.2 min-1 at pH 7.0 and 10 degrees C, which corresponds closely to the results of amide proton exchange studies with the [Cd7]- form of the protein. Finally, the 1H-1H distance constraints determined from nuclear Overhauser enhancement spectroscopy for human [Zn7]-metallothionein-2 were checked for compatibility with the [Cd7]-metallothionein-2 structure. Overall, although no direct method is available for identifying the metal-polypeptide co-ordinative bonds in the Zn(2+) containing protein, these measurements provided several independent lines of evidence showing that the [Zn7]- and [Cd7]- forms of human metallothionein-2 have the same molecular architecture. PMID- 1593629 TI - Crystal structure of the 2:1 complex between d(GAAGCTTC) and the anticancer drug actinomycin D. AB - The crystal structures of the 2:1 complex of the self-complementary DNA octamer d(GAAGCTTC) with actinomycin D has been determined at 3.0 A resolution. This is the first example of a crystal structure of a DNA-drug complex in which the drug intercalates into the middle of a relatively long DNA segment. The results finally confirmed the DNA-actinomycin intercalation model proposed by Sobell & co workers in 1971. The DNA molecule adopts a severely distorted and slightly kinked B-DNA-like structure with an actinomycin D molecule intercalated in the middle sequence, GC. The two cyclic depsipeptides, which differ from each other in overall conformation, lie in the minor groove. The complex is further stabilized by forming base-peptide and chromophore-backbone hydrogen bonds. The DNA helix appears to be unwound by rotating one of the base-pairs at the intercalation site. This single base-pair unwinding motion generates a unique asymmetrically wound helix at the binding site of the drug, i.e. the helix is loosened at one end of the intercalation site and tightened at the other end. The large unwinding of the DNA by the drug intercalation is absorbed mostly in a few residues adjacent to the intercalation site. The asymmetrical twist of the DNA helix, the overall conformation of the two cyclic depsipeptides and their interaction mode with DNA are correlated to each other and rationally explained. PMID- 1593630 TI - Normal mode refinement: crystallographic refinement of protein dynamic structure. I. Theory and test by simulated diffraction data. AB - A dynamic structure refinement method for X-ray crystallography, referred to as the normal mode refinement, is proposed. The Debye-Waller factor is expanded in terms of the low-frequency normal modes whose amplitudes and eigenvectors are experimentally optimized in the process of the crystallographic refinement. In this model, the atomic fluctuations are treated as anisotropic and concerted. The normal modes of the external motion (TLS model) are also introduced to cover the factors other than the internal fluctuations, such as the lattice disorder and diffusion. A program for the normal mode refinement (NM-REF) has been developed. The method has first been tested against simulated diffraction data for human lysozyme calculated by a Monte Carlo simulation. Applications of the method have demonstrated that the normal mode refinement has: (1) improved the fitting to the diffraction data, even with fewer adjustable parameters; (2) distinguished internal fluctuations from external ones; (3) determined anisotropic thermal factors; and (4) identified concerted fluctuations in the protein molecule. PMID- 1593631 TI - Normal mode refinement: crystallographic refinement of protein dynamic structure. II. Application to human lysozyme. AB - The dynamic structure of a protein, human lysozyme, is determined by the normal mode refinement of X-ray crystal structure. This method uses the normal modes of both internal and external motions to distinguish the real internal dynamics from the external terms such as lattice disorder, and gives an anisotropic and concerted picture of atomic fluctuations. The refinement is carried out with diffraction data of 5.0 to 1.8 A resolution, which are collected on an imaging plate. The results of the refinement show: (1) Debye-Waller factor consists of two parts, highly anisotropic internal fluctuations and almost isotropic external terms. The former is smaller than the latter by a factor of 0.72 in the scale of B-factor. Therefore, the internal dynamics cannot be recognized directly from the apparent electron density distribution. (2) The internal fluctuations show basically similar features as those predicted by the normal mode analysis, with almost the same amplitude and a similar level of anisotropy. (3) Correlations of fluctuations are detected between two lobes forming the active site cleft, which move simultaneously in opposite directions. This corresponds to the hinge-bending motion of lysozyme. PMID- 1593632 TI - Membrane protein structure prediction. Hydrophobicity analysis and the positive inside rule. AB - A new strategy for predicting the topology of bacterial inner membrane proteins is proposed on the basis of hydrophobicity analysis, automatic generation of a set of possible topologies and ranking of these according to the positive-inside rule. A straightforward implementation with no attempts at optimization predicts the correct topology for 23 out of 24 inner membrane proteins with experimentally determined topologies, and correctly identifies 135 transmembrane segments with only one overprediction. PMID- 1593633 TI - X-ray structure refinement and comparison of three forms of mitochondrial aspartate aminotransferase. AB - The X-ray crystal structures of three forms of the enzyme aspartate aminotransferase (EC 2.6.1.1) from chicken heart mitochondria have been refined by least-squares methods: holoenzyme with the co-factor pyridoxal-5'-phosphate bound at pH 7.5 (1.9 A resolution), holoenzyme with pyridoxal-5'-phosphate bound at pH 5.1 (2.3 A resolution) and holoenzyme with the co-factor pyridoxamine-5' phosphate bound at pH 7.5 (2.2 A resolution). The crystallographic agreement factors [formula: see text] for the structures are 0.166, 0.130 and 0.131, respectively, for all data in the resolution range from 10.0 A to the limit of diffraction for each structure. The secondary, super-secondary and domain structures of the pyridoxal-phosphate holoenzyme at pH 7.5 are described in detail. The surface area of the interface between the monomer subunits of this dimeric alpha 2 protein is unusually large, indicating a very stable dimer. This is consistent with biochemical data. Both subunit and domain interfaces are relatively smooth compared with other proteins. The interactions of the protein with its co-factor are described and compared among the three structures. Observed changes in co-factor conformation may be related to spectral changes and the energetics of the catalytic reaction. Small but significant adjustments of the protein to changes in co-factor conformation are seen. These adjustments may be accommodated by small rigid-body shifts of secondary structural elements, and by packing defects in the protein core. PMID- 1593634 TI - Optimal protocol and trajectory visualization for conformational searches of peptides and proteins. AB - Conformational searches by molecular dynamics and different types of Monte Carlo or build-up methods usually aim to find the lowest-energy conformation. However, this is often misleading, as the energy functions used in conformational calculations are imprecise. For instance, though positions of local minima defined by the repulsive part of the Lennard-Jones potential are usually altered only slightly by functional modification, the relative depths of the minima could change significantly. Thus, the purpose of conformational searches and, correspondingly, performance criteria should be reformulated and appropriate methods found to extract different local minima from the search trajectory and allow visualization in the search space. Attempts at convergence to the lowest energy structure should be replaced with efforts to visit a maximum number of different local energy minima with energies within a certain range. We use this quantitative criterion consistently to evaluate performances of different search procedures. To utilize information generated in the course of simulation, a "stack" of low energy conformations is created and stored. It keeps track of variables and visit numbers for the best representatives of different conformational families. To visualize the search, projection of multidimensional walks onto a principal plane defined by a set of reference structures is used. With Met-enkephalin as a structural example and a Monte Carlo procedure combined with energy minimization (MCM) as a basic search method, we analyzed the influence on search efficiency of different characteristics as temperature schedules, the step size for variable modification, constrained random step and response mechanisms to search difficulties. Simulated annealing MCM had comparable efficiency with MCM at constant and elevated temperature (about 600 K). Constraining the randomized choice of side-chain chi angles to optimal values (rotamers) on every MCM step did not improve, but rather worsened, the search efficiency. Two low-energy Met-enkephalin conformations with parallel Tyr1 and Phe4 rings, a gamma-turn around the Gly2 residue, and Phe4 and Met5 side-chains forming together a compact hydrophobic cluster were found and are suggested as possible structural candidates for interaction with a receptor or a membrane. PMID- 1593635 TI - Crystal structures of phosphate, iodide and iodate-inhibited phospholipase C from Bacillus cereus and structural investigations of the binding of reaction products and a substrate analogue. AB - The crystal structure of the complex formed between phospholipase C (PLC) from Bacillus cereus and inorganic phosphate (Pi), which is an inhibitor, has been determined and refined to 2.1 A resolution. The final R-factor is 19.7%. We have also studied the binding of two other inhibitors, iodide and iodate, to PLC. X ray data for these two complexes were collected to 2.8 A resolution during the search for heavy-atom derivatives. A series of screening experiments where PLC crystals have been treated with several reaction products and a substrate analogue were carried out to clarify the question of substrate binding. The results have so far been ambiguous but are discussed briefly. Phosphate and iodate are both found to bind to the three metal ions in the protein molecule, suggesting that these ions are involved directly in the catalytic process and thereby identifying the active site. PLC also binds nine iodide ions, eight of which are on the surface of the molecule and of lower occupancy. The ninth blocks the entrance to the active site cleft and is of higher occupancy. Altogether, these results suggest that the substrate, a phospholipid, is associated directly with the metal ions during catalysis. PMID- 1593636 TI - Crystallization and preliminary X-ray diffraction studies of the cobalamin binding domain of methionine synthase from Escherichia coli. AB - Crystals of a cobalamin-binding domain (M(r) = 28,000) have been grown in polyethylene glycol 6000 at pH 7.5, starting from solutions of intact (M(r) = 133,000) cobalamin-dependent methionine synthase. The crystals are orthorhombic in space group P2(1)2(1)2(1), with cell dimensions a = 96.9 A, b = 55.4 A, c = 103.8 A. For two molecules per asymmetric unit, the calculated VM value is 2.45 A3/Da. A native data set has been collected to 3 A resolution. PMID- 1593637 TI - Preliminary crystallographic data for stearoyl-acyl carrier protein desaturase from castor seed. AB - Recombinant stearoyl-acyl carrier protein desaturase (EC 1.14.99.6) from castor seed has been crystallized with polyethylene glycol 8000 as precipitant. The crystals are orthorhombic, space group P2(1)2(1)2(1) with cell dimensions a = 81.3, b = 146.4 and c = 197.7 A. The observed diffraction pattern extends to at least 2.5 A resolution. Rotation function calculations indicate a non crystallographic 3-fold rotation axis parallel to the crystallographic a-axis. Perpendicular to this axis, 2-fold rotation axes were found at 30 degrees intervals, i.e. maxima at kappa = 180 degrees, phi = 90 degrees and omega = 30 degrees and 60 degrees, respectively. Together with the packing density of the crystals (Vm = 2.4 A3/Da for n = 6), these results suggest, that the crystal asymmetric unit most likely contains a hexamer of desaturase subunits. PMID- 1593638 TI - Crystallization of an endochitinase from Hordeum vulgar L. seeds. AB - Higher plants contain several constitutively expressed proteins for protection against infections by viruses, bacteria and fungi. Here we report the crystallization of a polypeptide with antifungal activity, a 26,000 dalton endochitinase from barley (Hordeum vulgare L.) seeds, in a form suitable for high resolution X-ray analysis. Crystals were grown by vapor diffusion under several different conditions. The best crystals, obtained with ammonium sulfate as the precipitant, belong to the tetragonal space group P4(1)2(1)2 (P4(3)2(1)2), with cell dimensions a = b = 62.9 A and c = 96.0 A. The cell dimensions are consistent with one endochitinase molecule per asymmetric unit, and the crystals diffract to at least 2.0 A resolution. PMID- 1593639 TI - Genes encoding a histone H3.3-like variant in Arabidopsis contain intervening sequences. AB - Two genes encoding a particular H3 histone variant were isolated from Arabidopsis thaliana. These genes differ from the H3 genes previously cloned from Arabidopsis and other plants by several interesting properties: (1) the two genes are located close to each other; (2) their coding regions are interrupted by two or three small introns, the two closest to the initiation codon being located at the same place in the two genes; (3) another, long intron is located in the 5' untranslated region just before the initiation codon of gene I as deduced from the sequence of several corresponding cDNAs, and very likely also of gene II; (4) these genes do not show preferential expression in organs containing meristematic tissues contrary to the classical intronless replication-dependent histone genes, thus suggesting that their expression is not replication-dependent; (5) the protein encoded by both genes is the same and corresponds to a minor H3 variant highly conserved among all the plant species studied up to now. All these characteristics are common with the animal replication-independent H3.3 histone genes and it is assumed that the genes described here are the first example of the equivalent H3.3 gene family in plants. Interestingly, the promoter regions of the two genes have the same general structure as the Arabidopsis intronless genes. Possible implications on the regulation of H3 genes expression are discussed. PMID- 1593640 TI - Statistical evidence for remnants of the primordial code in the acceptor stem of prokaryotic transfer RNA. AB - The specificity of interaction of amino acids with triplets in the acceptor helix stem of tRNA was investigated by means of a statistical analysis of 1400 tRNA sequences. The imprint of a prototypic genetic code at position 3-5 of the acceptor helix was detected, but only for those major amino acids, glycine, alanine, aspartic acid, and valine, that are formed by spark discharges of simple gases in the laboratory. Although remnants of the code at position 3-5 are typical for tRNAs of archaebacteria, eubacteria, and chloroplasts, eukaryotes do not seem to contain this code, and mitochondria take up an intermediary position. A duplication mechanism for the transposition of the original 3-5 code toward its present position in the anticodon stem of tRNA is proposed. From this viewpoint, the mode of evolution of mRNA and functional ribosomes becomes more understandable. PMID- 1593641 TI - The boll weevil vitellogenin gene: nucleotide sequence, structure, and evolutionary relationship to nematode and vertebrate vitellogenin genes. AB - Boll weevil (Anthonomus grandis) eggs contain two yolk proteins, YP47 and YP160. Using anti-YP160 antiserum as probe, a partial-length complementary DNA (cDNA) was isolated from a lambda gt11 adult female cDNA library. A second partial length cDNA was isolated from a lambda gt10 adult female cDNA library by differential screening with male vs. female cDNAs. Northern blot analysis showed that each cloned cDNA hybridized to a 6-kb female-specific transcript. These cDNAs were used to probe a genomic library, and two overlapping genomic clones were obtained that span the boll weevil vitellogenin gene. The entire transcription unit was sequenced, and introns were mapped by a combination of primer extension experiments, S1 nuclease protection experiments, and polymerase chain reaction-mediated synthesis of two additional cDNA clones. Based on these data, the vitellogenin mRNA is 5511 nucleotides [plus a poly(A) tail of undetermined length] and specifies a provitellogenin of 1790 amino acids. The deduced protein has a Glu+Gln content of 16.3%, which is a relatively high value that is typical of most vitellogenins. Protein sequence similarities including Cys clusters conserved between boll weevil vitellogenin and Xenopus laevis A2 or Caenorhabditis elegans vit-5 vitellogenins indicated that the boll weevil protein is a member of the ancient nematode-vertebrate vitellogenin family. Moreover, the six introns in the boll weevil vitellogenin gene interrupt the coding region at positions closely or exactly corresponding to a subset of the positions of the 34 vertebrate vitellogenin introns, further supporting the argument for a common evolutionary relationship. This report represents the first complete nucleotide sequence and structural analysis of a nondipteran insect vitellogenin gene. PMID- 1593642 TI - The complete mitochondrial DNA sequence of the harbor seal, Phoca vitulina. AB - The nucleotide sequence of the mitochondrial DNA (mtDNA) of the harbor seal, Phoca vitulina, was determined. The total length of the molecule was 16,826 bp. The organization of the coding regions of the molecule conforms with that of other mammals, but the control region is unusually long. A considerable portion of the control region is made up of short repeats with the motif GTACAC particularly frequent. The two rRNA genes and the 13 peptide-coding genes of the harbor seal, fin whale, cow, human, mouse, and rat were compared and the relationships between the different species assessed. At ordinal level the 12S rRNA gene and 7 out of the 13 peptide-coding genes yielded a congruent topological tree of the mtDNA relationship between the seal, cow, whale, human, and the rodents. In this tree the whale and the cow join first, and this clade is most closely related to the seal. PMID- 1593643 TI - An evolutionary model for the duplication and divergence of esterase genes in Drosophila. AB - The esterase 5 (Est-5 = gene, EST 5 = protein) enzyme in Drosophila pseudoobscura is encoded by one of three paralogous genes, Est-5A, Est-5B, and Est-5C, that are tightly clustered on the right arm of the X chromosome. The homologous Est-6 locus in Drosophila melanogaster has only one paralogous neighbor, Est-P. Comparisons of coding and flanking DNA sequences among the three D. pseudoobscura and two D. melanogaster genes suggest that two paralogous genes were present before the divergence of D. pseudoobscura from D. melanogaster and that, later, a second duplication occurred in D. pseudoobscura. Nucleotide sequences of the coding regions of the three D. pseudoobscura genes showed 78-85% similarity in pairwise comparisons, whereas the relatedness between Est-6 and Est-P was only 67%. The higher degree of conservation in D. pseudoobscura likely results from the comparatively recent divergence of Est-5B and Est-5C and from possible gene conversion events between Est-5A and Est-5B. Analyses of silent and replacement site differences in the two exons of the paralogous and orthologous genes in each species indicate that common selective forces are acting on all five loci. Further evidence for common purifying selective constraints comes from the conservation of hydropathy profiles and proposed catalytic residues. However, different levels of amino acid substitution between the paralogous genes in D. melanogaster relative to those in D. pseudoobscura suggest that interspecific differences in selection also exist. PMID- 1593646 TI - Anomalous phylogeny involving the enzyme glucose-6-phosphate isomerase. PMID- 1593645 TI - Evolutionary origin of a Kunitz-type trypsin inhibitor domain inserted in the amyloid beta precursor protein of Alzheimer's disease. AB - The Kunitz-type protease inhibitor is one of the serine protease inhibitors. It is found in blood, saliva, and all tissues in mammals. Recently, a Kunitz-type sequence was found in the protein sequence of the amyloid beta precursor protein (beta APP). It is known that beta APP accumulates in the neuritic plaques and cerebrovascular deposits of patients with Alzheimer's disease. Collagen type VI in chicken also has an insertion of a Kunitz-type sequence. To elucidate the evolutionary origin of these insertion sequences, we constructed a phylogenetic tree by use of all the available sequences of Kunitz-type inhibitors. The tree shows that the ancestral gene of the Kunitz-type inhibitor appeared about 500 million years ago. Thereafter, this gene duplicated itself many times, and some of the duplicates were inserted into other protein-coding genes. During this process, the Kunitz-type sequence in the present beta APP gene diverged from its ancestral gene about 270 million years ago and was inserted into the gene soon after duplication. Although the function of the insertion sequences is unknown, our molecular evolutionary analysis shows that these insertion sequences in beta APP have an evolutionarily close relationship with the inter-alpha-trypsin inhibitor or trypstatin, which inhibits the activity of tryptase, a novel membrane-bound serine protease in human T4+ lymphocytes. PMID- 1593644 TI - Progressive sequence alignment and molecular evolution of the Zn-containing alcohol dehydrogenase family. AB - Sequences of 47 members of the Zn-containing alcohol dehydrogenase (ADH) family were aligned progressively, and an evolutionary tree with detailed branch order and branch lengths was produced. The alignment shows that only 9 amino acid residues (of 374 in the horse liver ADH sequence) are conserved in this family; these include eight Gly and one Val with structural roles. Three residues that bind the catalytic Zn and modulate its electrostatic environment are conserved in 45 members. Asp 223, which determines specificity for NAD, is found in all but the two NADP-dependent enzymes, which have Gly or Ala. Ser or Thr 48, which makes a hydrogen bond to the substrate, is present in 46 members. The four Cys ligands for the structural zinc are conserved except in zeta-crystallin, the sorbitol dehydrogenases, and two bacterial enzymes. Analysis of the evolutionary tree gives estimates of the times of divergence for different animal ADHs. The human class II (pi) and class III (chi) ADHs probably diverged about 630 million years ago, and the newly identified human ADH6 appeared about 520 million years ago, implying that these classes of enzymes may exist or have existed in all vertebrates. The human class I ADH isoenzymes (alpha, beta, and gamma) diverged about 80 million years ago, suggesting that these isoenzymes may exist or have existed in all primates. Analysis of branch lengths shows that these plant ADHs are more conserved than the animal ones and that class III ADHs are more conserved than class I ADHs. The rate of acceptance of point mutations (PAM units) shows that selection pressure has existed for ADHs, implying that these enzymes play definite metabolic roles. PMID- 1593647 TI - p53 mutations, another breast cancer prognostic factor. PMID- 1593648 TI - Author of Canadian Breast Cancer Study retracts warnings. PMID- 1593649 TI - Small study implicates PCBs in breast cancer. PMID- 1593650 TI - Western Europe unifying to tackle varied cancer problems. PMID- 1593651 TI - Cancer data bases expanding. PMID- 1593652 TI - 102nd Congress' attention to cancer remains significant. PMID- 1593653 TI - Effectiveness, costs, and cost-effectiveness of recruitment strategies for a mammographic screening program to detect breast cancer. AB - BACKGROUND AND PURPOSE: Since effective and affordable recruitment methods are essential for the widespread implementation of mammographic screening for detection of breast cancer, we studied the effectiveness, the costs, and the cost effectiveness of various recruitment strategies in the population targeted by a pilot Australian program that offered free mammography screening between 1988 and 1990. METHODS: We evaluated three public recruitment strategies--local newspaper articles, community promotion, and promotion to physicians--and five personal strategies--invitation letters with or without specified appointment times, either alone or with a follow-up letter, or telephone call to nonattenders. The effectiveness of public recruitment strategies was estimated from monthly attendance rates by Poisson regression analysis, while the probability of attendance in response to personal strategies was calculated using logistic regression analysis. Costs were determined by resource usage studies. The cost effectiveness ratios for personal strategies were determined using decision analysis. RESULTS: The costs in 1988-1989 Australian dollars per woman recruited were $22 for local newspaper articles and $106 for community promotion. No detectable increase in attendance resulted from promotion to physicians. When the cost of reserving an appointment was considered, the most cost-effective personal recruitment strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders. This strategy recruited 35.6% of women in the sample targeted and cost $10.52 per attendee. In comparison, the most effective personal recruitment strategy was a letter with a specified appointment time followed by a second letter to nonattenders, which recruited 44.1% of women at an average cost of $19.99 and a marginal cost of $59.71 per additional attendee. CONCLUSIONS: Personal recruitment strategies were more cost effective than public strategies. The most cost-effective personal strategy was an invitation letter without a specified appointment time, followed by a second letter to nonattenders. PMID- 1593654 TI - Case-control study of factors associated with human T-cell leukemia virus type I infection in southern Miyazaki, Japan. AB - BACKGROUND: An unusual age- and sex-specific distribution and a remarkably restricted geographic seroprevalence characterize human T-cell leukemia virus type I (HTLV-I) infection. Although the transmission routes of HTLV-I are known, these seroepidemiologic features cannot be fully explained. PURPOSE: This study was designed to identify potential characteristics associated with HTLV-I infection in a highly endemic Japanese community. METHODS: We evaluated occupational, residential, dietary, and medical histories in a case-control study conducted in two neighboring villages in southeastern Miyazaki Prefecture. One hundred forty-four case subjects and 276 control subjects, frequency matched by age, sex, and village, were interviewed. Village-specific profiles of demographic determinants of HTLV-I seroprevalence were generated using multiple logistic regression. RESULTS: Although a different pattern of factors was found for each village, occupations of the subjects and their fathers were associated with HTLV I infection in both communities--farming in village A and fishing and farming in village B. For village A, there was more than a twofold association both with residence in the township for 55 years or more and with living in a particular area within the village. In addition, case subjects were more likely to have a mother who was deceased (odds ratio = 1.7; 95% confidence interval = 0.96-2.9). CONCLUSIONS: HTLV-I infection is characterized by a high degree of microepidemicity in this population, with seroprevalence related to both sociologic and geographic determinants. Moreover, as carriers' mothers themselves have a higher probability of being HTLV-I positive, an increased mortality among those infected with the virus is suggested. PMID- 1593655 TI - Representativeness of the surveillance, epidemiology, and end results program data: recent trends in cancer mortality rates. AB - BACKGROUND: Mortality, incidence, and survival rates are the primary measures used by the National Cancer Institute (NCI) to monitor cancer in the United States. The Surveillance, Epidemiology, and End Results (SEER) data system collects data on all cancers diagnosed among residents in geographically defined populations, which comprise about 10% of the U.S. population. This data system is the major component of the NCI system for tracking these rates. Thus, it is important to assess the degree to which SEER data are representative of the entire U.S. population. PURPOSE: National data on mortality, but not on incidence or survival, are available from the National Center for Health Statistics. These data provide a census against which mortality data from the subset of the SEER regions may be compared. METHODS: Multivariate regression analyses of age adjusted mortality rates from 1975 to 1988, computed for the SEER areas and for the entire United States, were performed for race- and sex-specific data from 15 cancer sites. Representativeness was evaluated by testing for differences in trends and levels between the data from the U.S. population and those from the SEER Program. RESULTS: Data from the SEER regions reflected the correct direction of trend for all sites, although some race-, sex-, and site-specific differences existed for the magnitude of the trends and levels of mortality when compared with data from the U.S. population. CONCLUSIONS: The demonstration that data from the SEER population do occasionally yield mortality rates that differ from those for the entire U.S. population suggests that data from the SEER coverage population are, in some cases, not representative of the greater U.S. population. IMPLICATIONS: This issue is of particular relevance to the interpretation of incidence measures, computed from the SEER data, for which there is no national database. Future efforts should be directed at a better understanding of how the SEER population differs from the U.S. population so that SEER rates can be adjusted to be more nationally representative. PMID- 1593656 TI - Dacarbazine and outpatient interleukin-2 in treatment of metastatic malignant melanoma: phase II Southwest Oncology Group trial. PMID- 1593657 TI - Relationship between response and survival in patients with advanced ovarian cancer. PMID- 1593658 TI - Studies on single-dose toxicity of hydrophobically modified hydroxypropyl methylcellulose in rats. AB - Single-dose toxicological studies of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether) were conducted. A dispersion of HM-HPMC was administered to rats orally or by dermal application at doses up to 900 mg/kg. After the oral administration, the mean body weight of the 900 mg/kg group on the first day after administration was slightly but significantly lower (P less than 0.05) than that of the control group, and one rat had loose stools at 30 min. after the administration. No other abnormalities were noted. In the case of dermal application, no abnormalities were observed. No rats died, and no abnormalities in their organs were found by either route. In conclusion, there was no observed toxicity of HM-HMPC after oral or dermal administration at single dose up to 900 mg/kg under the conditions of these studies. PMID- 1593660 TI - Issues in AIDS training for substance abuse workers. AB - Workers in drug treatment programs need specialized training concerning acquired immune deficiency syndrome (AIDS) to meet the demands of their expanding roles. Initially, the treatment community failed to anticipate training needs fully, but now, comprehensive and systematic AIDS training programs must be developed. This article discusses the five steps in developing and implementing such programs: (a) assessment and information gathering, (b) curriculum development, (c) training of instructors, (d) training delivery, and (e) evaluation. PMID- 1593659 TI - Primary dermal and eye irritability tests of hydrophobically modified hydroxypropyl methylcellulose in rabbits. AB - Primary dermal and eye irritation tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether), a new cellulose derivative used as a thickener for topical pharmaceuticals and cosmetics, were conducted in rabbits. A dispersion of HM-HPMC (3%) was applied to intact and abraded skins and reactions were observed. A very slight erythema was observed in both skins and this polymer was categorized as a "mild irritant". In the eye irritation test, with a dispersion of the same concentration, it was categorized as "marginal" in unrinsed eyes and "negative" in rinsed eyes. PMID- 1593661 TI - Withdrawal from methadone maintenance. Impact of a tapering network support program. AB - This study assessed the impact of providing tapering and aftercare assistance to individuals addicted to heroin maintained on methadone. Participants were clients in six outpatient methadone maintenance clinics who expressed a motivation to withdraw from methadone and who met criteria predictive of success. Fifty-eight clients in three clinics had an enriched program available, whereas 56 clients in three matched comparison clinics received written materials only. No significant differences were found in the proportion of study participants who reached 0 mg or who reduced their dose during study participation. Discussion focuses on ways to improve the quality of methadone treatment in preparation for eventual withdrawal. PMID- 1593662 TI - Matching services to needs. Vocational services for substance abusers. AB - Problems with employment are common among individuals with substance use disorders, yet comprehensive vocational services are not generally available to them, and vocational interventions are often not matched to their specific needs. This article describes the wide range of vocational problems found among individuals with substance use disorders and the elements of a recently funded vocational program for patients in outpatient and residential drug and alcohol treatment programs. Data are presented describing program activity and documenting program effectiveness for the first 2 years of operation of the program. Three case histories are presented to illustrate the types of services delivered and the matching of services delivered to specific, identified client needs (see Case Histories). PMID- 1593663 TI - Attitudes toward mandatory human immunodeficiency virus testing and contact tracing. A survey of intravenous drug users in treatment. AB - Legal initiatives and treatment policies regarding mandatory human immunodeficiency virus testing and contact tracing often are considered without the input of those groups most affected by the proposed legislation. A survey of attitudes toward the testing and tracing issues was conducted on one such group- intravenous drug users in treatment. Interview and self-report questionnaire data were collected on 196 methadone-maintained patients from two Philadelphia clinics. Data indicate that although most methadone patients supported mandatory testing, their support appears to be influenced by past testing experience. That is, significantly more untested than tested individuals were opposed to the policy. Regarding contact tracing, data indicate that most patients with seronegative results supported tracing, but of the three patients with seropositive results who were surveyed, two were opposed to it. However, most seropositive and seronegative patients reported a willingness to comply with tracing if it were to become law. PMID- 1593664 TI - Different intake procedures. The influence on treatment start and treatment response--a quasi-experimental study. AB - Two hundred Norwegian substance abusers who consecutively applied for treatment in a hierarchical therapeutic community were divided into two different groups according to intake procedures: the intake group (IG) and the nonintake group (No IG). Using a prospective design, we found that beginners in the program were more often infected with human immunodeficiency virus and that they used amphetamine more frequently and alcohol less frequently than nonbeginners. The type of intake procedure did not influence the percentage of those who started in the program, but it increased the number of clients who completed Phase 1, the 1-year inpatient phase of the program. Twice as many clients in the IG completed Phase 1 compared to those in the No-IG. From a clinical point of view, we conclude that the IG procedure should be offered to all applicants but that the model should be developed more as a role induction strategy, in which learning practical coping skills to adjust to the treatment program is essential. PMID- 1593665 TI - Clinical course and outcome of substance abuse disorders in adolescents. AB - Seven percent (19 of 275) of children and adolescents not ascertained for seeking treatment received a DSM-III diagnosis of alcohol or drug use disorder. Their entire families were recruited into a research program designed to study the risk to offspring of parental psychopathology. The ages of those diagnosed were between 12 and 18 years. The drug and alcohol use disorders had a mean duration of 2 years, and the adolescents who remitted had a high likelihood of developing subsequent psychopathology. These adolescents also showed high rates of other psychiatric disorders. A high rate of alcoholism was found among their parents. PMID- 1593666 TI - Canadian Society of Otolaryngology--Head and Neck Surgery, 46th annual meeting. June 7-10, 1992, Quebec City, Quebec. Abstracts. PMID- 1593667 TI - The modern evaluation and treatment of hypertension: the causal role of the kidneys. PMID- 1593668 TI - A survey on incidental adrenal tumors in Japan. AB - A nationwide Japanese survey of 210 cases from 116 collaborating institutions demonstrated a dramatic increase in incidentally detected adrenal tumor from 4 cases in 1980 to 54 in 1988. The most common diagnosis was nonfunctioning cortical adenoma (69 cases), followed by pheochromocytoma (49). A total of 14 malignant tumors (6.7%) and 16 functioning benign cortical lesions was also found. Histological study revealed that functioning tumors were small and found in relatively young female patients, nonfunctioning cortical adenomas were of similar size but found in older patients, and all malignant tumors were larger than 6.5 cm. in diameter and occurred in patients 58 years or younger. These results indicate an increase in the occurrence of incidental adrenal tumor and the complexity of pathology. PMID- 1593669 TI - Percutaneous reduction of cyst volume of polycystic kidney disease: effects on renal function. AB - Percutaneous reduction of cyst volume was performed in 10 patients with autosomal dominant polycystic kidney disease and its effects on renal function were studied. Although creatinine clearance, urinary excretion of beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase, and renal uptake of 99mtechnetium dimercaptosuccinic acid did not change significantly, a transient increase in urinary protein and a decrease in inulin clearance were observed. Complications, such as hematuria, fever and decreases in hematocrit, were slight and transient in most patients. This procedure holds little promise for altering the course of polycystic kidney disease. PMID- 1593670 TI - Renal revascularization to preserve and restore renal function. AB - A total of 97 patients underwent 107 renal revascularization procedures for restoration and preservation of renal function. Of the 4 groups of high risk surgical patients that emerged an overall successful outcome was achieved in 83%, with a 6% mortality rate and an 11% morbidity rate. Renal revascularization for restoration and preservation of renal function can be performed safely with good results. The preoperative serum creatinine level was not predictive of the surgical outcome. Alternative bypass procedures are preferred. PMID- 1593671 TI - Long-term followup after nephron sparing surgery for renal cell carcinoma in von Hippel-Lindau disease. AB - We reviewed the long-term outcome of nephron sparing surgery in 9 patients with localized bilateral renal cell carcinoma and von Hippel-Lindau disease. One patient died of metastatic renal cell carcinoma 43 months postoperatively. One patient has not had recurrent tumor and was alive at 74 months postoperatively. The remaining 7 patients (mean followup 88 months) had local recurrence of tumor in the operated kidney and a secondary renal operation was done in 6 of them. Overall, 6 patients are free of tumor but only 3 of them retain functioning native renal parenchyma. We conclude that the results of nephron sparing surgery in patients with renal cell carcinoma and von Hippel-Lindau disease are less satisfactory than in patients with sporadic renal cell carcinoma. PMID- 1593672 TI - Experience with fossa recurrence of renal cell carcinoma. AB - We describe the surgical management and followup of 11 patients with local recurrence of renal cell carcinoma in the renal fossa, 10 of whom demonstrated no evidence of distant metastatic disease at the time of recurrence. Average interval to recurrence was 31 months from nephrectomy, with the majority of patients presenting with symptoms of weight loss, fatigue and lumbar discomfort. A total of 13 resections of recurrent carcinoma was performed with 3 immediate postoperative complications, including a retroperitoneal abscess, jejunal necrosis requiring resection and a duodenal obstruction requiring duodenojejunostomy. There were 2 postoperative deaths, 2 patients died of disseminated disease at 8 and 22 months, and 3 died of causes unrelated to cancer recurrence at 4 months, 6 months and 10 years. Four patients were without disease at a followup of 35, 46, 48 and 211 months. We include in this review a report on 1 patient who maintains a disease-free survival of 17 years after resection of a recurrent spindle cell carcinoma. We conclude that an aggressive surgical approach to recurrent renal cell carcinoma within the renal fossa can produce long-term disease-free survival and is justified when compared to the results reported for chemotherapy. PMID- 1593673 TI - Extracorporeal shock wave lithotripsy for ureteral calculi. AB - Second generation tubless lithotriptors allow for easy prone positioning of patients, resulting in increased use of extracorporeal shock wave lithotripsy (ESWL) for calculi in the ureter, especially in the mid and lower third portions. The 3-month stone-free rate with single stones using a Dornier HM3 and a Medstone STS lithotriptor in the upper ureter was 79% (316 patients) and 81% (188), respectively, while in the mid ureter it was 60% (20 patients) and 81% (32), respectively, and in the lower ureter it was 80% (5 patients) and 85% (26), respectively. The retreatment rate with single stones using the Dornier HM3 and the Medstone STS devices was 5% and 4%, respectively, in the upper ureter, 13% and 12%, respectively, in the mid ureter, and 0% and 5%, respectively, in the lower ureter. The second procedure rate after ESWL with single stones using the Dornier HM3 and the Medstone STS units was 6% and 6%, respectively, in the upper ureter, 15% and 16%, respectively, in the mid ureter, and 0% and 17%, respectively, in the lower ureter. Expectant management is still an acceptable method to treat small ureteral stones, and it is questionable whether ESWL is the appropriate treatment for lower third ureteral stones compared to equally effective and less expensive ureteroscopy. PMID- 1593674 TI - Treatment strategy for piezoelectric shock wave lithotripsy of upper ureteral calculi. AB - In situ piezoelectric lithotripsy monotherapy for upper ureteral stones is an attractive option because it can be conducted on an outpatient basis. Difficulty in calculus localization with ultrasound is the limiting factor. We reviewed our experience with 99 patients treated for upper ureteral calculi with the EDAP LT.01 lithotriptor. For stones above the lower renal border we achieved a 53% stone-free rate compared to 25% for calculi below the lower renal border. In situ piezoelectric lithotripsy of upper ureteral calculi may be considered for stones above the lower renal border. PMID- 1593675 TI - Endoureterotomy for treatment of ureteral strictures. AB - Advances in endosurgical technology have provided the urological surgeon with an alternative to open surgery for the treatment of ureteral strictures. We report the use of an endoscopic intraureteral incision (endoureterotomy) followed by balloon calibration to treat benign ureteral strictures in 13 patients. With an average subjective and objective followup among successful endoureterotomies of 20 months (all cases 12 months or greater), the overall success rate for this procedure is 62%. Of these patients 5 also received triamcinolone injections into the stricture bed following incision and dilation. This method appeared to influence favorably subsequent ureteral patency. The only operative complication was a urinoma, which resolved without intervention. Endoureterotomy appears to be a safe and reasonably effective modality for the treatment of ureteral stricture disease. PMID- 1593676 TI - Bladder function in elderly men with subclinical brain magnetic resonance imaging lesions. AB - Among 43 men more than 60 years old who complained of urinary irritative symptoms 40 had subclinical lesions in the brain on magnetic resonance imaging (MRI). Of these 40 patients 23 (57.5%) had detrusor hyperreflexia. The mean age of the patients with and without detrusor hyperreflexia was 75.8 and 68.2 years, respectively, which is a statistically significant difference. Patients with detrusor hyperreflexia were more likely to have lesions of the basal ganglia than patients without detrusor hyperreflexia. This study suggests that detrusor hyperreflexia, subclinical MRI lesions in the brain and aging are intimately interrelated. PMID- 1593677 TI - Bladder tumor control by abdominal ultrasound and urine cytology. AB - In 1983 our department introduced ultrasound with urine cytology instead of cystoscopy in the control of low risk bladder tumors. A total of 65 patients with exophytic, noninvasive bladder tumors (stage Ta, grades 1 to 3) underwent 340 ultrasound and urine cytology examinations. Positive diagnoses were confirmed by cystoscopy, and negative diagnoses were confirmed by either no clinical symptoms and negative ultrasound investigation at least 12 months later, negative cystoscopy or negative postmortem examination. Ultrasound revealed 13 tumors 2 to 25 mm. large and 11 were confirmed at cystoscopy. Ultrasound overlooked tumors in 2 patients. None of these tumors was larger than 2 mm. Urine cytology correctly indicated tumors in only 2 cases, falsely indicated tumors in 3 and missed tumors in 11. Results support the fact that ultrasound can continue to be used as an alternative to cystoscopy in selected bladder tumor control patients. Urine cytology had little predictive value in this study. PMID- 1593678 TI - Feasibility of transurethral resection for muscle-infiltrating carcinoma of the bladder: prospective study. AB - A prospective study was done to evaluate treatment of patients with muscle infiltrating bladder cancer by transurethral resection exclusively. Inclusion criteria for this study were histological confirmation of muscular bladder infiltration, endoscopic radical transurethral resection, disappearance of hardened areas after transurethral resection, and negative biopsies of the depth and periphery of the tumor bed. The study began in April 1981. The average followup in series 1 (April 1981 to December 1986, 59 patients) was 55.4 months. Actually, of the patients 31 (52.5%) are without evidence of recurrence and 28 (47.5%) have recurrent disease. Of the latter patients 11 (18.6%) had invasive bladder recurrence, including 7 (11.9%) who had recurrence at 3 months, which indicated clinical understaging. Three patients (5%) had metastases without bladder tumor. The remaining 14 patients (23.7%) had superficial bladder recurrence. The overall survival rate was 83% (49 of 59 patients) and 43 patients (72.8%) still retain the bladder. The present data are confirmed by the results of series 2 (December 1986 to August 1989). Therefore, the data would justify conservative management in a selected group of patients with muscle-infiltrating bladder cancer. PMID- 1593679 TI - Localized urethral tumors in women: indications for conservative versus exenterative therapies. AB - The objectives of this retrospective review were to evaluate patient and tumor characteristics, survival, patterns of failure and sequelae of therapy for women with urethral carcinoma. Primary urethral carcinoma was diagnosed in 33 women referred to the Washington University Medical Center and the Mallinckrodt Institute of Radiology, Radiation Oncology Center from November 1959 through June 1988. Treatment consisted of surgery alone in 6 patients, surgery and irradiation in 7, and irradiation alone in 20. Median followup was 4.7 years. The 5-year overall and progression-free survivals for all patients were 41% and 36%, respectively. Tumor location, size and T stage were predictive for survival. No patient with a lesion of greater than 4 cm. survived at 5 years if treated with irradiation alone, surgery alone or irradiation and nonexenterative surgery. Exenterative surgery plus irradiation was curative in 1 of 4 patients. Pelvic failures occurred in approximately 50% of all patients. Severe complications of therapy occurred in 30% of the patients treated with irradiation alone, 1 of 7 treated with surgery and irradiation, and 0 of 6 treated with surgery only. Surgery only or irradiation only may be curative in patients with lesions less than 2 cm. Larger lesions require a combination of surgery and irradiation. PMID- 1593680 TI - Success and patient satisfaction following the Stamey procedure for stress urinary incontinence. AB - A long-term followup survey to determine patient satisfaction following Stamey endoscopic vesicourethral suspension was obtained by means of a mail-in questionnaire. A total of 284 charts was reviewed and surveys were mailed, 17 of which were returned for lack of a forwarding address. A total of 192 replies was received for a 72% response rate. Overall improvement was found to be 82%, with approximately half of these patients found to be totally dry. When asked if they would be willing to go through the experience again 65% said they would. Criteria for the success or failure of the procedure were determined, weighing the degree of dryness against the previously mentioned question. With these criteria there was an overall success rate of 73%. Pulmonary disease, body weight greater than 86 kg., prior Marshall-Marchetti-Krantz procedure and concomitant abdominal hysterectomy lowered the success rate. Prior hysterectomy and concomitant vaginal hysterectomy had no influence on the success rate. PMID- 1593681 TI - A dynamic dual isotope radionuclear method of quantifying penile blood flow. AB - A new radionuclear method of quantifying arterial and venous blood flow of the penis is described. The technique is based on the simultaneous recording of the change in blood volume and venous outflow in the flaccid and erect states, which is produced pharmacologically. The change in penile blood volume is determined by measuring the change in the technetium-labeled red blood cell activity with time. Venous outflow is recorded with a xenon washout technique. The isotope data are used to compute arterial and venous flows with a complex computerized mathematical formula. Three basic blood flow patterns have been noted that distinguish normal patients from those with arterial insufficiency and venous leakage. The study is relatively easy and noninvasive to perform, and it appears to quantify penile blood flow accurately. PMID- 1593682 TI - Norepinephrine involvement in response to intracorporeal injection of papaverine in psychogenic impotence. AB - The levels of catecholamines in penile blood during a papaverine test were measured to investigate whether the secretion of endogenous catecholamines is involved in response to intracorporeal papaverine injection. The level of norepinephrine was higher in patients with psychogenic impotence than in the normal controls and patients with vasculogenic impotence (p less than 0.01), and it was significantly higher in negative responders than in positive responders in the psychogenic impotence group (p less than 0.001). There was no significant difference in the level of epinephrine among the groups. The false negative response to the papaverine test in psychogenically impotent men is believed to be derived from secretion of cavernous norepinephrine, which overwhelms the action of cavernous smooth muscle relaxation by papaverine. PMID- 1593683 TI - Squamous cell carcinoma of the penis. II. Treatment of the primary tumor. AB - The treatment of the primary tumor in 110 patients with squamous cell carcinoma of the penis seen between 1956 and 1989 was reviewed. Small tumors had generally been treated by penis conserving methods, such as circumcision, local excision and external radiotherapy alone or after circumcision or local excision. Since 1982 we have used the neodymium:YAG laser as a penis conserving method. In 51 patients (46%) penis conserving treatment had been performed and 59 (54%) had undergone some form of amputation. Overall, 16 of 110 patients (15%) had local recurrence. The risk of local recurrence after penis conserving therapy was significantly related to T category, with 10% local recurrences in stage T1 tumors in contrast to 32% and 100% in stages T2 and T3 tumors, respectively. All of the recurrences in patients with stage T1 tumors were strictly local and all were salvaged. In our view penis conserving therapy is a safe procedure in patients with stage T1 tumors and should always be attempted first. Amputation is considered to be overtreatment in these cases. Of 6 recurrences in the conservatively treated stage T2 disease group 4 were strictly local. These were all well or moderately differentiated tumors, not exceeding 3.5 cm. in diameter. We suggest penile conservation for this subgroup of T2 tumors. However, partial amputation is recommended for poorly differentiated stage T2 tumors. Local failure was observed in all stage T3 tumors treated with external radiation. In general, penis conservation in stage T3 tumors should not be attempted with the treatment modalities available to date. Comparing the different methods of penis conservation, used in 49 stages T1 and T2 tumors, no difference in local recurrence rate (18%) was observed among surgery, laser and external beam radiation. In view of the low morbidity, cutting and coagulation properties and minimal tissue changes, use of the neodymium:YAG laser would be our first choice of treatment modality. Penile conservation should be attempted only when frequent and long lasting followup is guaranteed, since local recurrences can appear as late as 8 years after primary treatment. PMID- 1593684 TI - Improvement in semen quality and sperm fertilizing ability after filtration through the L4 membrane: comparison of results with swim up technique. AB - The L4 filtration membrane was used at our laboratory on 30 semen specimens (19 from suspected subfertile patients and 11 from fertile donors) to assess changes in semen quality after routine sperm washing and swim up versus filtration through the L4 membrane. Of these 30 samples 17 (11 suspected subfertile patients and 6 fertile donors) were chosen to evaluate differences in sperm fertilizing ability between the 2 sperm preparation methods. Liquified specimens were analyzed on a Cell Soft semen analyzer. Semen specimens were divided equally, and 1 aliquot was processed by sperm washing and the swim up technique and the other by filtration. In all subjects the results of semen analysis and the hamster-egg penetration test showed significant improvement in sperm quality and fertilizing ability after filtration through the L4 membrane. Sperm motility was 58% after the swim up technique compared to 79% after filtration (p less than 0.0001) and velocity was 47 mu. per second after the swim up method compared to 52 mu. per second after filtration (p less than 0.048). Penetration rate and penetration index also showed a significant increase after filtration over values for the swim up method. Our results demonstrate that sperm filtration through the L4 membrane provides results superior to those of the traditional swim up technique. Due to significant savings in time associated with its use the L4 membrane can be used during sperm processing for intrauterine insemination and in vitro fertilization procedures. PMID- 1593685 TI - Is routine endocrine testing of impotent men necessary? AB - Endocrine screening of impotent men is performed in an effort to identify a treatable cause of impotence. However, the prevalence of endocrinopathy in this patient population is low. We determined whether any historical or physical findings obtained during the initial office visit would identify a subgroup of patients at risk for endocrinopathy to decrease the cost of endocrine screening. The results of routine endocrine screening of 330 consecutive impotent patients formed the basis of this study. A total of 7 patients (2.1%) had endocrinopathy. Testicular atrophy was observed in 5 of these 7 patients and 6 reported decreased libido. All of the patients with endocrinopathy had either decreased libido or bilateral testicular atrophy. Our results indicate that the cost of impotence evaluation can be decreased by screening only those patients with clinical signs of hypogonadism, that is either decreased libido or bilateral testicular atrophy. PMID- 1593686 TI - Semen quality and endocrine parameters after acute testicular torsion. AB - Of 16 postpubertal patients evaluated following testicular torsion 9 were treated with detorsion and bilateral orchiopexy (detorsion group), and 7 were treated with ipsilateral orchiectomy and contralateral orchiopexy (orchiectomy group). Each patient was evaluated with regard to semen quality, endocrine parameters (follicle-stimulating hormone, luteinizing hormone and testosterone) and the presence or absence of semen antisperm antibodies. These data were compared to similar data from a group of proved fertile semen donors. The semen quality in the detorsion group did not differ significantly from that of controls (p = 0.25) but follicle-stimulating hormone was significantly elevated compared with that of controls before and after stimulation with gonadotropin-releasing hormone. The orchiectomy group, which had been subjected to prolonged torsion (mean 69 hours), demonstrated a significant decrease in semen quality compared with semen quality in controls (p = 0.001), with average sperm density of only 29.0 million per ml. Baseline and post-stimulation levels of follicle-stimulating hormone in the orchiectomy group were also significantly abnormal when compared with those in controls and in the detorsion group. Our study demonstrates that testicular damage (changes in semen quality and/or endocrine parameters) occurs in the ipsilateral and contralateral testis following torsion, regardless of treatment modality. However, with early intervention by detorsion and testicular salvage, subsequent semen quality is likely to remain within normal limits. Late surgical intervention, even with removal of the nonviable testes, may result in significant impairment of semen quality. PMID- 1593687 TI - Ethanolamine oleate sclerotherapy for hydroceles and spermatoceles: a survey of 158 patients with ultrasound followup. AB - Sclerotherapy with 5% ethanolamine oleate was used to treat 102 hydroceles in 100 patients and 63 spermatoceles in 58 patients. Scrotal ultrasound examination was performed before the sclerotherapy and at each followup visit. Of the hydroceles 98% were cured completely and 68% were cured after only 1 sclerosant instillation, while 60% of the spermatoceles resolved completely and 33% partially, with 7% failures. No hydroceles recurred during an average followup of 43 months, whereas spermatocele recurred in 4 patients more than 1 year after successful treatment, with a mean followup of 46 months. Approximately half of the patients experienced pain after treatment, 3 had infection and 2 had hematoma. No changes in the structure or size of the testicles were found by ultrasound during followup. Ethanolamine oleate sclerotherapy is a safe, effective and economical form of outpatient therapy that can be recommended as primary treatment for hydroceles in adults and as an alternative to surgery for spermatoceles with 1 to 3 cysts in elderly men in whom fertility is not important. PMID- 1593688 TI - Lower incidence of unsuspected lymph node metastases in 521 consecutive patients with clinically localized prostate cancer. AB - Between 1983 and 1991 we saw 521 consecutive patients who elected to undergo radical prostatectomy for clinically localized prostatic carcinoma. We performed staging pelvic lymphadenectomy to avoid radical prostatectomy in patients with pelvic lymph node metastases who would be unlikely to be cured by the operation. However, we found that significantly fewer patients had lymph node metastases than historical reports would have led us to predict. Of 32 patients with clinical stage A1 disease none had positive nodes, compared to 2 of 61 (3.3%) with stage A2, 10 of 189 (5.3%) with stage B1 and 23 of 236 (9.7%) with stage B2 disease. We conclude that this lower incidence of nodal involvement relative to previous reports reflects a true change in the stage at which prostate cancer currently is diagnosed. We postulate that a higher index of suspicion, earlier detection, more aggressive intervention to establish the diagnosis, use of ultrasound guided prostate biopsies and more widespread screening for prostate cancer contribute to the lower incidence of occult lymph node metastases in patients with clinically localized prostate cancer. PMID- 1593689 TI - Impact of site release vaginal pH buffer cream on introital colonization by gram negative bacilli. AB - Colonization of the vaginal introitus by gram-negative bacilli is a critical event in the pathogenesis of bacteriuria and is promoted by an abnormal pH elevation. To determine whether a pH reduction might inhibit colonization we conducted a placebo controlled, crossover study of a site release vaginal pH buffer cream. A total of 12 premenopausal women with a history of urinary tract infection participated in the 12-week investigation. The mean introital pH during application of the placebo and buffer was 4.87 and 4.61, respectively (p less than 0.01). However, the percentage of positive introital cultures during application of the placebo and buffer (40.3 and 35.3, respectively) and the mean density of colonization (23,600 and 22,700 bacteria per ml., respectively) were not significantly different. The percentage of positive introital cultures and the mean colonization density were also not different during application of the placebo and buffer when the patients were retrospectively stratified as light and heavy colonizers. These data suggest that alteration of the introital pH within a range of 4.5 to 5.0 does not influence the growth of uropathogens on the vaginal mucosa. PMID- 1593690 TI - Recognition and management of delayed disruption vesicourethral anastomosis in radical prostatectomy. AB - We describe 2 cases of delayed disruption of the vesicourethral anastomosis after radical retropubic prostatectomy. Diagnosis was established by fluoroscopic examination. Cystoscopic fixation of a catheter intravesically with suprapubic monofilament suture through the dome of the bladder proved to be the key to resolution of the problem. PMID- 1593691 TI - Study on the correlation between subjective perception of bladder filling and the sensory threshold towards electrical stimulation in the lower urinary tract. AB - In 426 urodynamic patients with or without a neuropathic bladder sensation in the lower urinary tract was determined with 2 different investigation methods. During medium-fill cystometry the perception of filling was evaluated. At each sensation the bladder volume and detrusor pressure were noted. The electrical threshold was determined at different areas of the lower urinary tract with constant current stimulation. No correlation was found between the volume and pressure variables at which filling perception occurred and the electrical sensory thresholds. The levels of sensory threshold of the bladder and urethra in sensory urgency and hyposensitive bladder cases were not different from those seen in the normosensitive patients. Of the patients with disturbed or absent electrosensation 18% had a normal filling perception. Filling perception and electrosensation seem to correspond with 2 different areas of the sensory innervation of the lower urinary tract. To gain a maximum of information on bladder sensation, electrosensation as part of exteroceptive perception and filling perception as part of proprioception should be studied. PMID- 1593692 TI - Von Hippel-Lindau disease and renal cell carcinoma in a 16-year-old boy. AB - Von Hippel-Lindau disease is a rare autosomal dominant disorder. Kidney lesions occur in the majority of cases, with renal cell carcinoma noted in 40% and renal cysts in 60%. Renal cell carcinoma in von Hippel-Lindau disease is usually bilateral and occurs at an earlier age than in patients with sporadic renal cell carcinoma. We report on a 16-year-old boy who, to our knowledge, is the youngest patient to present with von Hippel-Lindau disease and renal cell carcinoma. Controversy currently exists regarding the nature of renal cysts in von Hippel Lindau disease and the optimal therapeutic approach (that is radical versus parenchymal sparing surgery). We review the histology of renal cysts and carcinoma, and discuss the rationale for selecting parenchymal sparing surgery. PMID- 1593693 TI - A 20-year experience with treatment of ectopic ureteroceles. AB - Between 1970 and 1990 a total of 37 patients (female-to-male ratio 3.6:1) was diagnosed and treated at our institution for ectopic ureterocele. Urinary tract infection was the most frequent mode of presentation (59%). Of the patients 54% were less than 3 years old at operation. Transurethral incision of ectopic ureterocele served only as a decompressive procedure for acutely ill infants and was followed with a high incidence (80%) of resultant vesicoureteral reflux. The elective surgical policy was individualized based on renal function and presence of vesicoureteral reflux. Overall results within the various groups were generally satisfactory regarding eradication of urinary tract infections, preservation of renal function and continence or treatment of vesicoureteral reflux. Upper pole heminephrectomy and partial ureterectomy were performed in 14 patients with 3 (21%) requiring reoperation, including only 2 (14%) subsequent reimplantations. Thus, we believe that an expectant approach to the lower urinary tract is well recommended in the majority of the patients with a poorly functioning ipsilateral renal segment. A modified technique of total reconstruction, performing only partial ureterectomy with double barrel reimplantation, was successful in 7 patients. PMID- 1593694 TI - Low loop cutaneous ureterostomy and subsequent reconstruction: 20 years of experience. AB - Between 1970 and 1990 we constructed low loop cutaneous ureterostomies in 50 patients with grossly dilated collecting systems. Patient age ranged from 6 days to 3 years. The indication for all urinary diversions was an anomaly of the lower urinary tract associated with marked ureteral dilatation considered to require decompression because of either urinary tract infections or renal functional impairment. Clinical and radiological followup was maintained between establishment of the cutaneous ureterostomy and complete reconstruction, and revealed marked improvement indistinguishable from that obtained by high diversions. Undiversion was performed after 3 to 69 months, usually simultaneously with definitive correction of the underlying anomaly. The main advantage of our presented technique is the opportunity to resect the distal ureteral limb and to perform simple ureteroneocystostomy using the proximal limb. Besides its technical simplicity, this technique obviates possible complications that may be attributed to ureteral anastomosis and compromised blood supply, thus, it is well recommended. PMID- 1593695 TI - Bilateral epidermoid cysts of the testicle. AB - An 11-year-old boy presented with bilateral testicular masses that consisted of hyperechoic centers with hypoechoic rims on ultrasound. Surgical exploration revealed bilateral epidermoid cysts. To our knowledge this is the first reported case of bilateral epidermoid cysts in a child. Recognition of this entity requires surgical confirmation but it may obviate removal of the testicle. PMID- 1593696 TI - The use of continent diversion in the management of rhabdomyosarcoma of the prostate in childhood. AB - Three children with rhabdomyosarcoma of the prostate treated with combination chemotherapy and radiation therapy underwent radical extirpation with continent diversion to the urethra. This urological procedure is technically feasible even in the small child (2 years old) and offers chance for cure. Radical cystectomy with continent diversion need not be considered as mutilating surgery. PMID- 1593697 TI - Lymphocytic glomerulitis in an Ask-Upmark kidney. AB - Lymphocytic glomerulitis in the Ask-Upmark kidney is a rare phenomenon. A case is reported in which the majority of the lymphoid cell infiltrate within the glomeruli was demonstrated to be of T cell origin. PMID- 1593698 TI - Functional obstructive uropathy: a significant factor in the hyponatremia of psychogenic polydipsia? AB - A case is presented of psychogenic polydipsia with hyponatremia. Prolonged observation of the patient revealed that episodes of hyponatremia correlated best with bladder failure and were promptly corrected by bladder catheterization. Bladder catheterization for underlying functional obstructive uropathy should be considered early in the treatment of patients with psychogenic polydipsia and hyponatremia. PMID- 1593699 TI - Lethal Fournier's gangrene following vasectomy. AB - A case is presented of a healthy young man who had Fournier's gangrene after standard bilateral vasectomy. Despite maximal treatment, including extensive necrectomy and broad-spectrum antibiotics, this complication was lethal. To our knowledge a lethal complication of vasectomy has not been reported in the literature. PMID- 1593700 TI - Persistent mullerian duct syndrome with transverse testicular ectopia and spermatogenesis. AB - Normal male sexual differentiation is dependent on at least 2 factors: 1) testosterone and 2) mullerian inhibiting factor. The absence of mullerian inhibiting factor is responsible for a rare form of male pseudohermaphroditism, the persistent mullerian duct syndrome or hernia uteri inguinale. Patients with this syndrome present with persistent mullerian structures and the syndrome may be associated with transverse testicular ectopia. Additionally, most patients have azoospermia. We report a case of persistent mullerian duct syndrome with transverse testicular ectopia in which sperm are documented in the ejaculate. PMID- 1593701 TI - Testicular fibroma. AB - A testicular fibroma in a 67-year-old man is reported. The tumor presented with expansive growth and myxoid areas. Atypias were absent. Differential diagnosis was made with immunohistochemical techniques that are useful for the diagnosis of nonspecialized gonadal stromal tumors. The origin of the tumor was probably in the interstitial or peritubular myofibroblasts. PMID- 1593702 TI - Intra-abdominal desmoid tumor: an unusual case of recurrent tumor in a testis cancer patient. AB - Recurrence of teratoma or carcinoma in testis cancer patients found to have teratoma at post-chemotherapy retroperitoneal lymphadenectomy is well recognized. We report a case of an intra-abdominal desmoid tumor discovered 2 years following post-chemotherapy retroperitoneal lymphadenectomy in a testis cancer patient who had teratoma at the time of lymphadenectomy. To our knowledge this is the first case of an intra-abdominal desmoid tumor discovered in this setting. The characteristics and treatment considerations of this unusual tumor are described. Desmoid tumor should be included in the differential diagnosis of tumor recurrence in testis cancer patients previously subjected to post-chemotherapy retroperitoneal lymphadenectomy. PMID- 1593703 TI - Cystadenoma of the seminal vesicle: case report and literature review. AB - A benign fibroepithelial and cystic tumor of the seminal vesicle is described in a 63-year-old man. The symptoms, macroscopic appearance, microscopic characteristics, immunophenotype prognosis and complications of this rare benign tumor are discussed, and 9 previously reported cases are reviewed. Several terms have been used to describe benign fibroepithelial tumors of the seminal vesicle. We suggest that the term cystadenoma is the most appropriate. PMID- 1593704 TI - Psoas abscess: case report and review of the literature. AB - Psoas muscle abscess is rare and presents a diagnostic challenge requiring a high index of suspicion. We report an unusual case of primary psoas abscess caused by Proteus mirabilis. Primary psoas abscess is most commonly present in children and is usually caused by Staphylococcus aureus. A total of 434 cases of psoas abscess has been reported. The subject is discussed noting the differences between primary and secondary cases, and emphasizing the importance of ultrasound and computerized tomography guided drainage of psoas abscess. A flow chart for the evaluation and management of primary and secondary abscess is presented, taking into consideration the success rate of the various methods of treatment described in the literature. PMID- 1593705 TI - Re: Adrenal hemorrhage in the newborn with evidence of bleeding in utero. PMID- 1593706 TI - Re: Expanding contractures of the tunica albuginea due to Peyronie's disease with temporalis fascia free grafts. PMID- 1593707 TI - Re: Intermittent torsion: associated with horizontal lie of the testicle. PMID- 1593709 TI - Re: Cancer control following anatomical radical prostatectomy: an interim report. PMID- 1593708 TI - Re: Repair of a traumatically amputated penis with return of erectile function. PMID- 1593710 TI - A plea to rename potency-sparing radical surgery as erection-sparing radical surgery. PMID- 1593711 TI - Re: Transitional cell carcinoma of the prostate. PMID- 1593712 TI - Phospholipase C activation by endothelin-1 and noradrenaline in isolated penile erectile tissue from rabbit. AB - The effects of endothelin-1 and noradrenaline on phospholipase C activity in the rabbit isolated corpus cavernosum were investigated by measuring the accumulation of inositol phosphates. Both endothelin-1 and noradrenaline caused a time- and concentration-dependent increase in the accumulation of 3H-inositol phosphates in preparations prelabelled with 3H-myo-inositol. The reaction was slow in onset with no significant accumulation of 3H-inositol phosphates, including inositol trisphosphate, demonstrable during the first 15 minutes. At 60 minutes, the mean increases in 3H-inositol inositol phosphates induced by 3 x 10(-7) M endothelin-1 and 10(-3) M noradrenaline amounted to 341 and 530% of time-matched controls, respectively. However, when given at concentrations having the same contractile amplitude on rabbit corpus cavernosum, there was no difference in the amounts of 3H-inositol phosphates generated by endothelin-1 and noradrenaline. Prazosin (10( 6) M) significantly inhibited the stimulatory effect of noradrenaline on phosphoinositide hydrolysis. Pretreatment with 10(-6) M nimodipine did not reduce the increases in 3H-inositol phosphates induced by 3 x 10(-7) M endothelin-1 and 10(-3)M noradrenaline. Also in Ca(2+)-free medium, both agonists had significant stimulatory effects on phosphoinositide turnover, although under this condition, the responses were greatly reduced. The results suggest that exogenous endothelin 1 and noradrenaline activate phospholipase C in corpus cavernosum, and that this mechanism is partly independent of extracellular Ca2+. Considering the slow onset of action, phospholipase C activation is probably not directly involved in rapid contractile events, but may be of importance in the long-term regulation of penile smooth muscle tone. PMID- 1593713 TI - Intravesical Evans strain BCG therapy: quantitative immunohistochemical analysis of the immune response within the bladder wall. AB - Previous studies have demonstrated that is is the local immune response which is of importance for the anti-tumour activity of BCG therapy. We have investigated this by quantitative immunohistochemical analysis of serial bladder mucosal biopsies taken before, during and after an eight week course of intravesical Evans strain BCG therapy and three monthly thereafter in 16 patients (15 extensive CIS and one extensive G2pTa papillary tumour). This particular group of patients had a 67% complete response rate at six months post-treatment. The main findings on immunohistochemical analysis were the universal induction of MHC Class II antigens by urothelial cells which was statistically significant up to 6 months after completion of therapy, coupled with a T cell dominated cystitis. Increases in CD3+ T cell infiltration of the lamina propria and that of the CD4+ "Helper" subset which predominated were significant up to 3 months post-therapy and these cells showed evidence of increased immunological activation as shown by increased interleukin-2 receptor and MHC Class II antigen expression. There were also significant increases in CD68+ macrophage and the incidence of CD22+ B cell aggregates but CD57+ NK cells were sparse both before and after therapy. The degree of mononuclear cell infiltration for all markers examined (except CD57) was significantly greater in those biopsies in which the urothelial cells expressed MHC Class II antigens than in those that did not. Also the degree of T cell infiltration (CD3, CD4 and CD8) was significantly greater in the eight patients deemed to have had a complete response compared to those seven with a partial response or treatment failure. These results are discussed in terms of possible mechanisms of action for BCG therapy and in particular the role of enhanced antigen presentation by tumour cells. PMID- 1593714 TI - The effect of two new semi-synthetic glycosaminoglycans (G871, G872) on the zeta potential of calcium oxalate crystals and on growth and agglomeration. AB - The effects of two new semisynthetic glycosaminoglycans (GAGs), G871 and G872, on the crystal growth and agglomeration of calcium oxalate monohydrate (COM) were studied in artificial urine in vitro. A constant composition crystallization system and a seeded crystal growth system were used to measure the rate of crystal growth and degree of agglomeration. The zeta potential on the crystal surface was measured using a Coulter DELSA 440 doppler electrophoretic light scattering analyzer. The previously reported GAG analogue, sodium pentosan polysulphate (SPP or SP54), was studied as a reference inhibitor of crystallization using the same systems. All three substances had a concentration dependent effect on the zeta potential and on the rate of crystal growth and agglomeration of COM in artificial urine. G872 had a significantly greater effect than either G871 or SPP on all the measured parameters. It is suggested that semisynthetic GAGs, such as those reported in this paper may be of use in the prevention of the recurrence of calcium oxalate stones. PMID- 1593715 TI - The impact of iatrogenic urothelial trauma on urinary levels of transforming growth factor-alpha. AB - Growth factors are important regulators of epithelial cell biology. We postulated that iatrogenic bladder manipulations may alter urinary growth factor levels and thereby influence both normal and neoplastic urothelium. Using a rat model we studied the effects of various types of urothelial injury, corresponding to bladder catheterization, cystoscopy, fulguration, and chronic indwelling catheterization (Groups B, C, D, and E respectively) on levels of urinary transforming growth factor-alpha (uTGFa). Urine samples collected circa the time of transurethral bladder manipulation were analyzed for protein, creatinine (Cr), and TGFa. Results in experimental groups were compared to control values (group A). Peak concentrations of uTGFa uniformly occurred on the day of surgery and represented 176%, 196%, 726%, 461% and 916% increases relative to pre-operative values in groups A, B, C, D and E respectively. Total uTGFa (nM/mg. Cr) was maximal on experimental day 0 in groups A, B, C, D and day 2 in group E (102%, 114%, 227%, 290% and 976% change from baseline respectively). Compared to control, levels of uTFGFa were significantly elevated on day 0 in the fulguration group, and day 0 and 2 in the chronic catheterization animals (p less than .05). Nonsignificant elevations of uTGFa relative to control were based in all groups through day 7. The chronic catheterization levels remained significantly elevated, compared to control, over the duration of the study (ANOVA, p less than .05). Urinary protein levels correlated with the severity of the injury and showed a strong positive correlation with uTGFa (p = .0001). This study demonstrated a clear impact of iatrogenic urothelial trauma on urinary levels of TGFa. PMID- 1593716 TI - A comparison of two continent catheterizable vesicocutaneous techniques. AB - In a rabbit model we describe and compare two continent catheterizable diversion techniques for which the bladder is intact and the stoma is situated in the lower abdomen. Both mechanisms are formed from a short segment of ileum; one utilizes the principles of the encircling loop technique as described by Koff and the second, the Kock principle (intravesical nipple). Both models were evaluated for the following parameters: ease of catheterization (87%, 79% respectively), continence (91%, 86% respectively), and ease of construction. We present evidence that both techniques are applicable to the clinical setting. PMID- 1593717 TI - Site of deafferentation and electrode placement for bladder stimulation: clinical implications. AB - Based on the clinical experience of treating neurogenic bladders by the electrical stimulation of the ventral sacral roots, neuroanatomical and neurophysiologic studies were designed to study the mechanism of detrusor sphincter dyssynergia during electrical stimulation of the sacral roots. An experimental model was developed to decrease the stimulation response of the pelvic floor and external urethral sphincter muscles while preserving bladder contraction. The significance of the site of deafferentation and electrode implantation was evaluated under functional and clinical aspects. Our results indicate that a combination of intradural deafferentation and extradural electrode implantation may offer maximal deafferentation efficiency with minimal surgical risk. Intradural deafferentation is facilitated by a consistent arrangement of sacral roots with the dorsal roots running laterally to the ventral roots at the site of their exit from the dura. Detrusor-sphincter dyssynergia can be reduced by selective division of ventral sacral rootlets innervating the striated musculature of the pelvic floor and the urethral sphincter. PMID- 1593718 TI - In vitro study of the effect of hyperthermia on normal bladder cell line and on five different transitional cell carcinoma cell lines. AB - Intraluminal hyperthermia is potentially useful in the management of superficial bladder cancer. The potential inhibitory effect of hyperthermia on various human bladder cancer cell lines, normal human bladder cells and the murine MBT-2 bladder cancer cell line has been studied in vitro. These cell lines were exposed for one hour to 43 +/- 0.5C and compared to controls. Cell survival was assessed comparing the cell growth curve and colony formation. The human transitional cell carcinoma (TCC) cell lines vary in their sensitivity to heat. MGH-U1 was the most heat sensitive cell line. The human A-1698, CUB-2, UM-UC-3 and the murine MBT-2 lines were heat insensitive. We conclude that the cytocidal effect of hyperthermia in bladder transitional cell carcinoma is variable. Further experiments using the combination of hyperthermia and intravesical anticancer agents are in progress. PMID- 1593720 TI - Dilation vs. dilatation: a brief history. PMID- 1593719 TI - Erectile dysfunction due to atherosclerotic vascular disease: the development of an animal model. AB - An animal model was developed to study the pathophysiology of erectile dysfunction due to atherosclerotic vascular disease. Thirty one New Zealand white male rabbits were divided into control (n = 5) and treatment groups (n = 26). The control group was placed on a regular diet while the treatment group underwent balloon de-endothelialization of the aorto-iliac arteries and received 1.6% cholesterol and 4% triglyceride diet for eight weeks. After eight weeks in the control animals (n = 5), blood levels of cholesterol, triglycerides and low density lipoproteins, radiologic studies as well as hemodynamic parameters of erectile function were all normal. In the surviving treatment animals (n = 21) after the same time period, a significant increase in blood levels of cholesterol, triglyceride and low density lipoprotein were observed. In addition, 62% of these animals developed hypertension which was not observed in the control group. Angiographically, 10 animals (48%) demonstrated severe atherosclerotic lesions (75% to 100% occlusion of common or internal iliac arteries on one side and over 50% occlusion of the opposite side), five (24%) had moderate lesions (50 to 75% luminal occlusion of right and left common iliac or internal iliac arteries) and 6 revealed minimal lesions (less than 50% occlusion of the right and left common iliac or internal iliac arteries). Of the 15 animals with 50% or greater luminal occlusion of the iliohypogastric arteries, erectile dysfunction was found in 93% of cases. Due to the development of erectile dysfunction in 33% of animals with minimal occlusive lesions, it appears that factors, other than large vessel luminal occlusion, may exist in this animal model which adversely influence erectile function. This model may therefore be of further benefit in the study of other factors associated with atherosclerosis and impotence, such as the possible concomitant hypercholesterolemic and atherosclerotic-induced alterations in the local reactivity of corpus cavernosum smooth muscle and lacunar space endothelial cells. PMID- 1593721 TI - Hospital staff, victims, families cope with life-altering effects of violence. PMID- 1593722 TI - Adolescents may experience home, school abuse; their future draws researchers' concern. PMID- 1593723 TI - ACOG renews domestic violence campaign, calls for changes in medical school curricula. PMID- 1593724 TI - From the Surgeon General, US Public Health Service. PMID- 1593725 TI - From the Centers for Disease Control. Cigarette smoking among adults--United States, 1990. PMID- 1593726 TI - The lethal botulinum toxic shot syndrome. PMID- 1593727 TI - The violence our violent country does to others. PMID- 1593728 TI - The use of race in medical research. PMID- 1593729 TI - The use of race in medical research. PMID- 1593730 TI - The use of race in medical research. PMID- 1593731 TI - The risk of redefining rationing. PMID- 1593732 TI - Preventing PID: try monogamy. PMID- 1593733 TI - Warning patients about alcohol abuse. PMID- 1593734 TI - New drugs: are we being double-billed? PMID- 1593735 TI - Primary care physicians' response to domestic violence. Opening Pandora's box. AB - OBJECTIVE: To explore primary care physicians' experiences with domestic violence victims to determine the barriers to problem recognition and intervention in the primary care setting. DESIGN: Ethnography, a qualitative research method involving the use of open-ended, semistructured interviews. SETTING: An urban health maintenance organization serving a predominantly white, middle-income population. PARTICIPANTS: Thirty-eight physicians, predominantly family practitioners (89%), were interviewed. RESULTS: Analysis of the interviews revealed that physicians found exploring domestic violence in the clinical setting analogous to "opening Pandora's box." Their issues include lack of comfort, fear of offending, powerlessness, loss of control, and time constraints. CONCLUSION: This study revealed several barriers that physicians perceived as preventing them from comfortably intervening with domestic violence victims. These issues need to be addressed in training programs. Further studies should be done to assess generalizability of these findings to other groups of physicians. PMID- 1593736 TI - Attitudes of primary care physicians toward corporal punishment. AB - OBJECTIVE: The purpose of this study was to determine whether or not family physicians and pediatricians support the use of corporal punishment. The frequency with which these physicians offer anticipatory guidance on discipline was also studied. DESIGN: Self-report survey, mailed to study participants. PARTICIPANTS: The sample for this study was 800 family physicians and 400 pediatricians, randomly selected from the Ohio State Medical Board's roster of family physicians and pediatricians. Physicians with a subspecialty were excluded. Participants who did not return their surveys received a second, and if necessary, a third mailing of the survey. After three mailings, a total of 619 physicians (61%) completed a survey. MAIN OUTCOME MEASURE: Participants were considered to support corporal punishment if they would tell a parent in their medical practice that spanking would be an appropriate response to any one of a series of childhood misbehaviors presented in the survey. RESULTS: Of family physicians, 70% (95% confidence interval [CI], 66% to 75%) support use of corporal punishment. Of pediatricians, 59% (95% CI, 52% to 66%) support corporal punishment. Of pediatricians, 90% (95% CI, 86% to 94%) indicated that they include discipline issues either always or most of the time when providing anticipatory guidance to parents. Significantly fewer family physicians (52%; 95% CI, 47% to 57%) indicated that they discuss discipline either always or most of the time when providing anticipatory guidance (P less than .01). CONCLUSIONS: Most family physicians and pediatricians support the use of corporal punishment in spite of evidence that it is neither effective nor necessary, and can be harmful. Pediatricians offer anticipatory guidance on discipline more often than family physicians. PMID- 1593737 TI - Parental alcohol use, problem drinking, and children's injuries. AB - OBJECTIVE: Millions of US children are exposed to parents who are problem drinkers, yet there is little evidence about the effect of parental alcohol consumption on children's health. The aim of this study was to assess the association between children's injuries and parental drinking. DESIGN: Survey of a nationally representative sample of the US population by household interview. PARTICIPANTS: 12,360 children and parents from single-family households, with data from the Alcohol and Child Health supplements to the 1988 National Health Interview Survey. MAIN OUTCOME MEASURE: Serious injuries--injuries resulting in hospitalization, surgical treatment, missed school, one half day or more in bed. RESULTS: Children of mothers categorized as problem drinkers had 2.1 times the risk of serious injury as children of mothers who were nondrinkers (95% CI, 1.3 to 3.5). Other measures of mothers' alcohol consumption (ie, average, maximum, and self-rated consumption) were unrelated to child injuries, as were all measures of fathers' drinking. Children of women who were problem drinkers married to men rated as moderate or heavy drinkers had a relative risk of serious injury of 2.7 (95% CI, 0.8 to 8.6) compared with children of nondrinkers. CONCLUSION: Children of women who are problem drinkers have an elevated injury risk; children with two parents who are problem drinkers are at higher risk. Further research is needed on potential mechanisms and interventions. Primary prevention might be enhanced if physicians elicited information about parental drinking, helped secure appropriate treatment, and participated in public health efforts to reduce the deleterious effects of alcohol. PMID- 1593738 TI - Origins and clinical relevance of child death review teams. AB - Interagency child death review teams have emerged in response to the increasing awareness of severe violence against children in the United States. Since 1978, when the first team originated in Los Angeles, Calif, child death review teams have been established across the nation. Approximately 100 million Americans or 40% of the nation's population now live in counties or states served by such teams; most have been formed since 1988. Multiagency child death review involves a systematic, multidisciplinary, and multiagency process to coordinate and integrate data and resources from coroners, law enforcement, courts, child protective services, and health care providers. This article provides an introduction to the unique factors and magnitude of suspicious child deaths, and to the concept and process of interagency child death review. Future expansion of this process should lead to more effective multiagency case management and prevention of future deaths and serious injuries to children from child abuse and neglect. PMID- 1593739 TI - Assessing for abuse during pregnancy. Severity and frequency of injuries and associated entry into prenatal care. AB - OBJECTIVE: To assess the occurrence, frequency, and severity of physical abuse during pregnancy and associated initiation of prenatal care. DESIGN: Stratified, prospective cohort analysis. SETTING: Public prenatal clinics in Houston, Tex, and Baltimore, Md. PARTICIPANTS: Total population-based sample of 691 black, Hispanic, and white pregnant women. All of the women were urban residents and most of the Hispanic women were Mexican American. All participants were invited into the study at the first prenatal visit and were followed up until delivery. MAIN OUTCOME MEASURE: Identification of abuse status. RESULTS: A three-question Abuse Assessment Screen detected a 17% (1/6) prevalence of physical or sexual abuse during pregnancy, which is more than double all previous published reports. When evaluated against nationally tested research instruments, the three-question screen that was asked at the first prenatal visit was sensitive and specific to abuse status. Abuse was recurrent, with 60% of abused women reporting two or more episodes of assault. Location of abuse focused on the head. Frequency and severity of abuse and potential danger of homicide was appreciably worse for white women. Abused women were twice as likely as nonabused women to begin prenatal care during the third trimester. CONCLUSIONS: A simple clinical assessment screen completed by the health care provider in a private setting and with the male partner absent is as effective as research instruments in identifying abused women. Straightforward, routine clinical assessment is recommended as essential in preventing potential trauma, interrupting existing abuse, and protecting health. PMID- 1593740 TI - The epidemiology of murder-suicide. AB - OBJECTIVE: To review the epidemiology, patterns, and major determinants of murder suicide and to discuss the clinical and research strategies for identifying the individuals at greatest risk for this type of violence. DATA SOURCES: Data were obtained from English-language articles based on searches using MEDLINE (from 1966), PsychINFO (from 1967), and EMBASE (from 1974) programs. In addition, relevant articles, books, and monographs identified from the reference list of retrieved articles were reviewed. STUDY SELECTION: Case-control studies, descriptive epidemiologic surveys, and case series were chosen for review. DATA EXTRACTION: Because of the limited scope of the pertinent research literature, all data relevant to the incidence, demographics, circumstances, and precipitants of murder-suicide were summarized by the authors. DATA SYNTHESIS: Murder-suicide occurs with an annual incidence of 0.2 to 0.3 per 100,000 person-years and accounts for approximately 1000 to 1500 deaths yearly in the United States. The annual incidence of these events is relatively constant across industrialized nations and has not significantly changed over several decades. The principal perpetrators are young males with intense sexual jealousy, depressed mothers, or despairing elderly men with ailing spouses. The principal victims are female sexual partners or consanguineous relatives, usually young children. Clinical depression, specific motivations such as male sexual proprietariness or maternal salvation fantasies, and a history of previous suicide attempts are important in explaining underlying psychopathological mechanisms. CONCLUSIONS: Murder-suicide occupies a distinct epidemiological domain that overlaps with suicide, domestic homicide, and mass murder. These events may be categorized into one of only several phenomenologic typologies that share similar demographics, motivations, and circumstances. Despite the disruption of families and communities caused by murder-suicide, there are no standardized operational definitions, validated taxonomic systems, or national surveillance networks for these events, all of which are needed to develop prevention strategies. PMID- 1593741 TI - Violence against women. Relevance for medical practitioners. Council on Scientific Affairs, American Medical Association. AB - Evidence collected over the last 20 years indicates that physical and sexual violence against women is an enormous problem. Much of this violence is perpetrated by women's intimate partners or in relationships that would presumably carry some protective aura (eg, father-daughter, boyfriend girlfriend). This violence carries with it both short- and long-term sequelae for women and affects both their physical and psychological well-being. The high prevalence of violence against women brings them into regular contact with physicians; at least one in five women seen in emergency departments has symptoms relating to abuse. However, physicians frequently treat the injuries only symptomatically or fail to recognize the injuries as abuse. Even when recognized, physicians are often without resources to address the needs of abused women. This report documents the extent of violence against women and suggests path that the physician community might take to address the needs of victims. PMID- 1593742 TI - Physicians and domestic violence. Ethical considerations. Council on Ethical and Judicial Affairs, American Medical Association. PMID- 1593743 TI - Violence, values, and gender. PMID- 1593744 TI - From the Office of the General Counsel. Corporal punishment in the schools. PMID- 1593745 TI - Importance of coronary artery spasm in alcohol-related unexplained syncope. AB - To examine the role of coronary artery spasm in patients with syncope after alcohol ingestion, we performed an intracoronary ergonovine provocation test in 7 male patients (39 to 73 years old, mean 54 years) with alcohol-related syncope which remained unexplained despite noninvasive cardiovascular and neurological examinations. No patients had structural heart disease or significant coronary artery stenosis. Ergonovine was continuously infused into each coronary artery at a rate of 10 micrograms/min for up to 5 min. Coronary artery spasm with ST segment elevation was induced in 4 of 7 patients. Chest pain before syncope or history of chest pain were not present in 3 of 4 patients with a positive ergonovine test. Multivessel coronary artery spasm was induced in 3 patients. One patient presented with triple vessel coronary artery spasm progressing to near syncope as a result of profound hypotension and ventricular tachycardia during provocation. Coronary artery spasm was promptly relieved by intracoronary isosorbide dinitrate infusion. All patients with a positive ergonovine test were treated with calcium antagonist and did not experience syncope during follow-up. These results suggest that coronary artery spasm is one of the important causes of syncope after alcohol ingestion. PMID- 1593746 TI - Long-term changes of infarct-related lesions. Comparison of angiograms in recent and remote phases. AB - Coronary angiograms recorded in the recent phase of an acute myocardial infarction in 73 patients were compared with those taken in the remote phase at least 12 months from the onset of the infarction. The infarct-related lesions of 23 patients (32%) showed a regression of 20% or more. Analysis of recent-phase angiograms proved that any one of several features (long-segment narrowing, intraluminal thrombus, flap-like structure or atheromatous ulceration) was present more frequently in the lesions showing a marked regression (18/23, 78%) than in the lesions without regression (15/40, 38%) (p less than 0.01). Thus, the narrowings of infarct-related lesions seen on the recent-phase angiograms regress frequently. The possibility of regression can be predicted from the angiographic features. PMID- 1593747 TI - Mitral valve surgery in the presence of pulmonary hypertension. AB - Mitral valve surgery was performed in 59 patients with severe pulmonary hypertension (average systolic pulmonary artery pressure 77.1 +/- 18.6 mmHg; range 50-115 mmHg) between 1983 and 1990. Thirty-eight patients had been subjected to mitral valve replacement, 16 patients both mitral and aortic valve replacement, and 5 patients had open mitral commissurotomy, with an operative (30 day) mortality of 5.0%. These 3 deaths happened during the early postoperative period. Survivors were followed up for a period ranging from 6 months to 7 years with a mean of 36 months. Four late deaths (7.1%) occurred in patients with valve replacement. Actuarial survival was 93 +/- 3% at 5 years, and 90.7 +/- 4.4% at 7 years. Right ventricular catheterization was performed on 14 patients a mean of 38 months following operation. Systolic pulmonary artery pressure had decreased from a mean of 77.1 +/- 18.6 to 39.7 +/- 14.0 mmHg (p less than 0.001) and 90% of the survivors were in New York Heart Association Class 1 or II compared to 23.7% preoperatively. The clinical and hemodynamic findings in this series suggest that severe pulmonary hypertension is not a contraindication, and pulmonary hypertension decreases significantly after mitral valve surgery. PMID- 1593748 TI - A simple ergometer for 31P NMR spectroscopy during dynamic forearm exercise in a whole body magnetic resonance imaging system. AB - The purpose of this study was to construct a simple ergometer for the 31P NMR spectroscopic study of dynamic forearm exercise in a whole body magnetic resonance imaging system and to evaluate the total system and the physiological response to this type of exercise using a multistage protocol. The system consisted of a completely nonmagnetic assembly including a rope, pulley and weights. The work of lifting weights was quantitated. The exercise protocol of 1 min increments in work load enabled subjects to reach maximal effort. Phosphocreatine decreased linearly with an increase in work load and was accompanied by a fall in pH and an increase in lactate level in the antecubital vein of the exercising forearm; concomitantly, there was a slight increase in whole body oxygen uptake and heart rate. Spectroscopy gave reproducible results using this exercise protocol. These results demonstrate that this system provides a reliable means for performing 31P magnetic resonance spectroscopy studies during forearm exercise. PMID- 1593749 TI - Acute hemodynamics of pimobendan in chronic heart failure. A comparative crossover study of captopril and pimobendan. AB - Acute hemodynamics of pimobendan were compared to captopril in a crossover trial in patients with chronic heart failure (NYHA II-III). Heart failure had been stabilized by conventional therapy with diuretics and digitalis for more than 2 weeks. Patients receiving vasodilators were excluded. The hemodynamics were analyzed using a Swan-Ganz catheter at the bedside during drug administration. Following an intravenous injection of 2.5 mg of pimobendan, there was a significant increase in heart rate and decrease in mean pulmonary artery pressure, total pulmonary resistance, mean arterial pressure, systemic vascular resistance and mean right atrial pressure 2 hours after the injection. Captopril (12.5 mg, orally) significantly decreased mean arterial pressure, systemic vascular resistance and double product 2 hours after administration. In this study, the inotropic effect was evaluated through the relation between the stroke volume index and diastolic pulmonary artery pressure, and also between the stroke volume index and mean arterial pressure. Although decreases of diastolic pulmonary artery pressure and mean arterial pressure were seen with both drugs, the differences in stroke volume index were not significant. In comparison with captopril, the acute hemodynamics of pimobendan are characterized as follows: 1) the systemic arteriovasodilating effects of the two drugs were equal, 2) the pulmonary arteriovasodilating effect of pimobendan was marked, 3) a venodilating effect, documented through a decrease of mean right atrial pressure, was seen only with pimobendan. This study concluded that pimobendan is a stronger arterio venodilator than captopril. PMID- 1593750 TI - Importance of spontaneous closure of the ventricular part in atrioventricular septal defect. AB - The clinical features, hemodynamic changes and prognosis of 21 children with simple atrioventricular septal defect (3 associated with patent ductus arteriosus) were studied during a follow-up period of 1 month to 13 3/12 years (median 3 years). Six patients had spontaneous closure of the ventricular part of the defect within 22.2 +/- 27.7 months (Group I). The symptoms and signs of failure to thrive, frequent respiratory tract infections and congestive heart failure were more common in patients without spontaneous closure of the ventricular part of atrioventricular septal defect (Group II) than in patients in Group I. The Qp/Qs ratio, pulmonary vascular resistance and pulmonary to systemic resistance ratio were also higher in Group II than in Group I. In spite of a higher postoperative mortality rate and a higher incidence of transient complete heart block, the children in Group II also had a significantly higher (p less than 0.005) preoperative mortality rate than those in Group I. In conclusion, if the ventricular part of the atrioventricular septal defect closed or was closing spontaneously, symptoms and signs were less severe and there was a better prognosis. PMID- 1593751 TI - Constant efficiency versus variable economy of cardiac contraction. AB - An intriguing aspect of cardiac mechanoenergetics is the smaller variability of the contractile efficiency than the energy economy of force. We theoretically speculated about this dissociation by relating the mechanical efficiency with Po/a (the curvature of the force-velocity curve) in Hill's characteristic equation of muscle; Po/a is known to change with the energy economy and inversely with Vmax and myosin ATPase activity. The analysis showed that the variability is smaller for the mechanical efficiency than for Po/a and that the energy economy changes approximately with (Po/a)3. These theoretical relations may partly explain the small variability of the empirically observed contractile efficiency under various experimental conditions which are known to widely change the energy economy. PMID- 1593752 TI - Comparative studies of the systemic hemodynamics and myocardial oxygen consumption of FRC 8653, a new Ca++ channel blocker, and nifedipine in anesthetized dogs. AB - Effects of FRC 8653, a new dihydropyridine derivative, on regional blood flow, cardiac function and myocardial oxygen consumption were examined and compared with those of nifedipine in anesthetized open-chest dogs. Intravenous administration of FRC 8653 at doses of 1, 3 and 10 micrograms/kg dose-dependently decreased aortic pressure and increased aortic, vertebral and coronary blood flow similar to nifedipine. No significant change was observed in left ventricular end diastolic pressure, left ventricular positive dP/dt and heart rate following i.v. administration of FRC 8653. Myocardial oxygen consumption was dose-dependently decreased by FRC 8653. When changes in mean aortic pressure and aortic and coronary blood flow were compared at the same dose of 10 micrograms/kg i.v., both FRC 8653 and nifedipine showed almost the same degree of reduction of mean aortic pressure, but the time from drug administration to peak responses and the duration for which half the maximal effects were maintained, were significantly longer with FRC 8653 than nifedipine. Results suggest that FRC 8653 may be useful for the treatment of patients with hypertension and ischaemic heart disease. PMID- 1593753 TI - Left ventricular thrombosis due to acquired protein C deficiency diagnosed by two dimensional echocardiography. AB - We present a patient with left ventricular thrombus diagnosed by two-dimensional echocardiography. Thrombosis was due to acquired transient protein C deficiency which was caused by impaired liver function due to hepatitis, sepsis and heart failure. With proper treatment the thrombus disappeared on the fourth day. Eighteen weeks later the protein C level returned to normal. We recommend echocardiographic evaluation and follow-up of suspected cases for intracardiac thrombus. The measurement of protein C level in such cases is proposed. This is the first case with left-sided cardiac thrombus associated with protein C deficiency in the medical literature. PMID- 1593754 TI - Double atrial response to a single ventricular extrastimulus in a patient with Wolff-Parkinson-White syndrome. AB - Electrophysiological examination in a 39-year-old male disclosed an accessory pathway between the right atrium and the right ventricle and AV nodal dual pathways. Atrial and ventricular extrastimuli induced paroxysmal supraventricular tachycardia (PSVT), which was shown to be AV reciprocating tachycardia. Double atrial response was noted during ventricular extrastimuli at V1V2 of 280 msec and V1V2 of 250 msec. The first atrial response is considered to have been transmitted in a retrograde fashion in the accessory pathway, and the second atrial response similarly in the slow pathway of the AV node. PMID- 1593755 TI - Repair of torn aortic root with the left atrial appendage. AB - A narrow aortic root and a small aortic annulus made aortic valve replacement in a 35-year-old female patient with calcified aortic stenosis rather difficult. At the end of the procedure, it was noticed that the aortic root was badly torn. The tear started at the end of the aortotomy incision, near the commissure between the non-coronary and left coronary cusps, ran flush with the prosthetic ring and extended beneath and a few millimeters beyond the ostium of the left coronary artery. Only a thin rim of the aortic wall was left proximally, which was not strong enough to support the sutures. The aorta was repaired using a pericardium covered Goretex patch, bolstered by the left atrial appendage. PMID- 1593756 TI - [Clinical laboratory and expert system]. AB - Computer-based expert systems are designed to incorporate the knowledge of a human expert such that the computer program will solve problems in a manner similar to the human expert. The systems can be applied fruitfully to many phases of the laboratory testing, including order entry, specimen collection, analysis, result verification, and reporting. Interpretive reporting by means of expert systems is useful for influencing physician's use of laboratory and they offer potential help for clinical decision making. Although much of the early work in the clinical laboratory involved stand-alone expert systems, approaches that integrate more closely with laboratory information system or hospital information system are being used. A short review on the technology of expert system with an emphasis on the roles played by clinical laboratory is made. A trial system dealing with thyroid diseases, based on interpretation of hormonal levels (TSH, Total and Free T3, T4), is described. PMID- 1593757 TI - [Memorial speech: historical retrospect of the development of clinical pathology in Japan for these 40 years]. AB - The speaker who had been appointed professor at the department of clinical pathology in 1951 (which was the first one established in medical schools in Japan) told the development of this medical science retrospectively in Asahikawa, Hokkaido (1991). At the start (1950s) clinical pathology was not readily accepted as an educational unit in medical schools because of reasonless misunderstanding by anatomical pathologists and traditional clinicians. However, later (1970s) it became favored by practical physicians under the leadership of the Japan Medical Association. This situation caused foundation of central clinical laboratories and department of clinical pathology in medical schools. In 1980s cooperative participation of the personnel of engineering sciences in clinical pathology brought rapid progress of test techniques, such as various automatic procedures. In the mean time, the central laboratories are being transformed into a factory equipped with versatile automatic instruments, and expending money for its investment which is too much a hospital can afford. As a result many of the clinical tests are prone to be ordered to the clinical laboratory centers outside the hospital. In this way too many and too much tests are served without meticulous attention of diagnostic and cost effectiveness. To eliminate this wasteful use of tests the speaker proposed the following policy. Laboratory tests should be selected in a small number carefully on the basis of diagnostic and cost effectiveness so that they may be ordered to the laboratory in sets to facilitate clinical laboratory interpretation by use of a computer (CALD) which prints out the possible disease groups relevant to each patient on a report sheet. PMID- 1593758 TI - Pathology in Europe. PMID- 1593759 TI - [Tumor markers of ovarian cancer]. AB - Many of the recently developed tumor markers are carbohydrate antigens, and are clinically useful for the diagnosis of ovarian cancers. These carbohydrate antigens can be classified into three major categories; core protein-related antigens (CP-RA), core of carbohydrate chain-related antigens (CSC-RA) and periphery of carbohydrate chain-related antigens (PSC-RA). CA125, CA602, and CA130 belong to CP-RA; CA602, CA72-4, and sialyl Tn to CSC-RA; and CA19-9 and sialyl LewisX (SLX), to PSC-RA. The positive rates of CP-RA in the sera of patients with ovarian epithelial cancers are usually very high except in the case of mucinous cystadenocarcinomas. Meanwhile, those of CSC-RA are higher than those of CP-RA in the sera of mucinous cystadenocarcinoma patients, and the false positive rate of CSC-RA is lower than that of CP-RA in benign ovarian tumors. The diagnostic efficiency of PSC-RA is inferior to that of CA-RA and CSC-RA. Multi variate analysis has revealed that the combination assay of these CP-RA and CSC RA markers is the most effective among the carbohydrate antigen assays for the diagnosis of epithelial ovarian cancers. beta-core fragment (beta-CF), a fragment of the hCG beta-subunit missing its carboxyterminal peptide, is often detected in the urine of ovarian cancers, indicating that urine can be a good sample source for ovarian cancer detection. PMID- 1593760 TI - [Relationship between tumor markers and clinical symptoms in ovarian cancer]. AB - To assess their usefulness in the prediction of tumor recurrence, we retrospectively examined the accuracy of preoperative diagnosis of ovarian cancer based on tumor markers on 279 patients with benign and malignant ovarian tumors treated at our department. Of the tumor markers examined, CA125 had the highest diagnostic accuracy, suggesting that it is the most useful marker in the diagnosis of ovarian cancer. TPA and IAP were found to be relatively useful, the tumor markers recently identified, CA72-4 had a high true positive rate. We examined the factors affecting the cut-off value for CA125 in healthy volunteers and determined the corrected cut-off value. Using this value, we assessed the usefulness of CA125 in distinguishing between benign and malignant tumors and in predicting tumor recurrence. Factors found to affect the serum CA125 level included pregnancy, menstrual cycle, dysmenorrhea, menopause, and blood type. Using our equation for women over 40 years of age, we obtained a specific cut-off level of 16 U/ml for postmenopausal women, which was found to more accurately distinguish between ovarian tumors in this age group than did the conventional cut-off level of 35 U/ml, which has been used for all age groups. Furthermore, the specific cut-off level predicted tumor recurrence about 2 months earlier than did the conventional cut-off value. In tumor recurrence, CA125 had risen gradually but was within the normal range. Tumor recurrence was observed in all patients who had shown continuous three-stage elevation of CA125 within the normal range. PMID- 1593761 TI - [Induction of manganese superoxide dismutase in ovarian carcinoma]. AB - A monoclonal antibody against manganese superoxide dismutase (Mn-SOD) was assessed for its use in detecting a marker for epithelial ovarian carcinoma. An enzyme-linked immunosorbent assay has been developed to detect serum Mn-SOD. With this assay, only 1.7% of the 240 healthy females tested had more than 130 ng per milliliter of serum Mn-SOD. In contrast, 39 of 66 patients (59.1%) with epithelial ovarian carcinoma showed high levels of Mn-SOD. The serum Mn-SOD increased according to the clinical stage and declined to reflect the effect of therapy. The determination of Mn-SOD levels proved to be a clinical useful marker for monitoring the response to treatment and to early detection of the recurrence of epithelial ovarian carcinomas. PMID- 1593762 TI - [Assessment of ovarian tumors by transvaginal scanning and clinical significance of ultrasonic examination in postoperative follow up]. AB - A hundred and sixty cases of ovarian tumor were preoperatively examined by transvaginal (TV) and Transabdominal (TA) scanning and accuracy of the assessment for histologic type was compared. We also examined 56 cases of postoperative ovarian cancer by ultrasonography to detect recurrent lesions. Positive predictive values for serous cysts and endometrial cysts were higher with TV than TA. Sensitivity for cancer was also high, but false negative rate was lower with TV than TA. The results showed that scatter from small particles and small mural echo in the cystic mass are visualized more clearly with TV, so that TV is more useful for assessing histological type of ovarian tumors. Sensitivity and specificity of ultrasonographic examination for detecting intraperitoneal recurrent lesions were 88.2% and 97.4%, respectively. Those for extraperitoneal lesions were 86.7% and 97.6%. Ultrasonography is suggested to be useful for detecting recurrence ovarian cancer especially for experitoneal lesions, as laparoscopy is not effective for such lesions. PMID- 1593763 TI - [Progress of leukocyte research]. AB - Over 170 years ago Metchnikoff described the bacteriocidal activity of leukocytes. It has been clarified that leukocytes play an important role in first defense mechanism against infection due to microorganism. Leukocytes immigrate to the lesion, which various microorganisms invade across mucosal barrier, and phagocyte and kill ingested microorganisms. The inability of the chronic granulomatous disease (CGD) granulocytes to generate superoxide has prompted the analysis of NADPH oxidase responsible for superoxide generation. The study on CGD has provided profound informations into NADPH oxidase system of leukocytes. Recruitment leukocytes to inflammatory lesion is essential for the inflammatory process, and it is regulated by various chemotactic factors and the adhesion molecules interaction between leukocytes and endothelium of vessels. Identification of interleukin-8 (IL-8) to be one of chemotactic cytokines and its gene cloning offered the progressive understanding for the immigration mechanism of leukocytes from vessels to inflammatory lesion. On the other hand, LFA-1 deficiency revealed that emigration, adhesion and phagocytosis of leukocytes are associated closely with the adhesion molecules on their surfaces. More recently, the cytokine networks of myelopoiesis or inflammatory process have been clarified. Among various cytokines, the cloning of G-CSF has provided the clinical application of rhG-CSF for neutropenic patients who may be induced by the treatment with anticancer agents. This symposium focused on above-mentioned items for an important aspect of neutrophil research. PMID- 1593764 TI - [A newly discovered chemotactic factor for neutrophil: interleukin 8]. AB - A potent peptide chemotactic factor for leukocytes has been purified from lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cell culture supernatant, followed by its cDNA cloning and its expression in Escherichia coli. This factor was named interleukin-8 (IL-8) since it is produced by various kinds of cells in response to inflammatory stimuli including LPS, IL-1 and tumor necrosis factor (TNF) and has pleiotropic effects on T lymphocytes and basophils as well as neutrophils. The receptors for IL-8 contain seven transmembrane domains as revealed by cDNA cloning, suggesting that they are a member of superfamily of G-protein-coupled receptors. The transcription of IL-8 gene is presumed to be regulated by the action of two kinds of transcription factors, NF-kappa B and NF-IL6, both of which are supposed to be involved in the activation of acute phase reactant genes, suggesting that the activation of IL-8 gene is a good model for elucidating the molecular mechanism of the transcription of these genes. In various kinds of diseases in which neutrophilia or neutrophil infiltration is found, the increase of IL-8 level in body fluids is often observed. The clarification of the role of IL-8 in the process of these inflammatory diseases will lead to the development of a novel kind of anti inflammatory or immunomodulating agents. PMID- 1593765 TI - [Laboratory tests in primary care medicine: "essential laboratory tests" (2). Usefulness of hematological, biochemical and serological tests in diagnosis of new outpatients]. AB - We evaluated diagnostic utility of the hematological, biochemical and serological tests comprised in the "essential laboratory tests" advocated by the Japan Society of Clinical Pathology in 1,026 new patients visiting the outpatient unit of Comprehensive Medicine, National Defense Medical College. Of 750 evaluable patients, 52 showed anemia associated with such conditions as ulcer or cancer of digestive tract, inflammatory disease, or renal failure. Leukocytosis (greater than 9,000/microliters) was found only in 25 of 112 CRP-positive (greater than 0.3 mg/dl) patients, suggesting bacterial infection. Forty-four patients showed hypoproteinemia and/or hypoalbuminemia indicating chronic conditions including liver and inflammatory disease. Elevation of serum creatinine level was found in 4 patients subsequently diagnosed with renal failure, whereas 32 patients demonstrated elevated BUN. After application of the "essential laboratory tests", 97 patients were diagnosed with hyperlipidemia (total cholesterol greater than 230 mg/dl and/or triglyceride greater than 250 mg/dl). Determination of serum enzyme activity was useful not only for the diagnosis of liver dysfunction or biliary tract disease but also for those of hematological malignancies or myogenic disorders; however, in patients with abnormal values of LDH, gamma-GT and ALP, clinical significance was not clarified in 53%, 38% and 59%, respectively. These results indicate that the "essential laboratory tests" are useful in the following aspects of primary care medicine: for (1) estimation of the degree or nature of infection or inflammatory status; (2) classification of anemia and its relation to underlying diseases; (3) evaluation of patient general condition and protein-producible function of liver; (4) evaluation of renal function; (5) ambulatory screening for metabolic diseases such as hyperlipidemia; and (6) diagnosis of liver and biliary tract diseases. PMID- 1593766 TI - [Effect of various sampling condition on the measurement of circulating TSH and free thyroxine]. AB - We report here the effect of various sampling and storage condition on the measurement of circulating TSH and free thyroxine (FT4). Blood samples were obtained from five normal subjects using four kinds of sampling tubes; plane glass tube, glass tube containing serum separator, and glass tube containing EDTA 2Na or heparin-sodium. We stored whole blood, serum or plasma at low temperature (4-8 degrees C) or at room temperature (20-25 degrees C) from one hour to thirteen days. Both values of EDTA-plasma TSH and FT4 were significantly lower than those of serum samples, EDTA-plasma TSH value was increased gradually during storage at room temperature but not at low temperature. Serum or plasma FT4 values were decreased during storage at room temperature but not at low temperature. In conclusion, circulating TSH and FT4 values are influenced by different sampling tubes and, serum or plasma TSH and FT4 are not always stable under the storage condition at room temperature. Serum samples obtained by using plane glass tube and kept at low temperature give us more reliable values of TSH and FT4. PMID- 1593767 TI - [Immunohistological study of reactive follicular hyperplasia of lymph node in childhood]. AB - Reactive follicular hyperplasia (RFH) of lymph nodes, which is often found in the peripheral nodes in children, is usually caused by viral, bacterial, or other specific infections, and sometimes complicated with dermatopathic lesions, or immunological disorders. Those nodal lesions might result from one of the various immunological reactions to some antigen. In this histologic and immunohistologic study, we mainly investigated the cells in the involved nodes. As the results, in the cases of the conspicuous follicular hyperplasia, there were prominent increase of the T-cell with positive UCHL1, the antigen presenting cells with positive S100 protein in T-nodule, and the B-cell with positive L26 in germinal center and cortical sinuses. The nodes with conspicuous follicular hyperplasia also showed foci of infiltration of the polymorphous leukocytes or the lysozyme positive mono-macrophages in the cortical sinuses at the early or acute stage. Decreasing the grade of RFH, the polymorphous or the macrophage infiltration disappeared, while S100 protein positive histiocytes remained as the persistent nodules or aggregates in the cortical sinuses. It was also noted that the B-cells with polyclonal surface immunoglobulins, IgM, kappa, or lambda, increased in number in the case of conspicuous RFH. The RFH might be the result of increased activity of the cellular and humoral immunity, with which T-cells, B-cells, antigen presenting cells, and mono-macrophages are concerned.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593768 TI - [Free A-I apolipoprotein and bound A-I apolipoprotein determined by "multiple" crossed immunoelectrophoresis in patients with acute hepatitis and obstructive jaundice]. AB - Crossed immunoelectrophoresis (CIEP) using anti-A-I apolipoprotein antiserum gave a large immunoprecipitin peak of bound A-I apolipoprotein (bound A-I) with alpha mobility and a small immunoprecipitin peak of free A-I with pre-beta mobility. The concentrations of free A-I and bound A-I were determined in 7 patients with acute hepatitis (AH) and in 3 patients with obstructive jaundice (OJ) by a "multiple" CIEP designed so that four samples could be simultaneously determined on one agarose-gel plate. The concentrations of bound A-I and free A-I in 40 normolipidemic healthy individuals were 126.5 +/- 16.3 mg/dl and 7.2 +/- 2.2 mg/dl (means +/- SD), respectively. The characteristic findings in CIEP for apo A I obtained on patients with AH and OJ were the pronounced decrease in bound A-I and the appearance of double peaks with pre-beta mobility, the one on the cathodic side of which was proved to be bound A-I. Hypo-A-I apolipoproteinemia recognized in patients with AH and OJ was due to the decrease of bound A-I. In parallel with the recovery of the hepatic function after treatment, the reduced concentration of bound A-I was gradually normalized, accompanied by restoration of the level of total apo A-I. However, the concentration of free A-I increased in AH and OJ complicated with hypertriglyceridemias, and was not affected by the change in liver function. These findings suggest that free A-I originates from organs other than the liver whereas bound A-I certainly originates from the liver. The determination of bound A-I is clinically useful in AH and OJ. PMID- 1593769 TI - [Determination of human IgG subclass by EIA]. AB - The human IgG subclasses have specific characteristics in response to respective antigens, and determination of their characteristics is important in analysis of infectious, autoimmune and other diseases. We developed quantitative EIA (ELISA) assays for Japanese human IgG subclasses with excellent reproducibilities using monoclonal antibodies. The assays enable determinations between 0.4 ng/ml and 2,000 ng/ml. The serum IgG subclass levels (mean+SD) in healthy adults are as follows: IgG1, 5.93 + 2.07 mg/ml (59.94%); IgG2, 3.36 + 1.84 mg/ml (32.97%); IgG3, 0.30 + 0.19 mg/ml (3.07%); and IgG4, 0.22 + 0.15 mg/ml (2.34%). Excellent correlation was obtained between total IgG level measured by EIA using anti-whole human serum and the sum of the four IgG subclasses (IgG1+IgG2+IgG3+IgG4). Samples from every patient with M protein of IgG1 and IgG2 types shown by M band on immunoelectrophoresis also had the highest level in four IgG subclasses. PMID- 1593770 TI - [A study on creatine uptake into human erythrocytes: relation to erythrocyte aging]. AB - In order to assess the relation between creatine uptake into human erythrocytes and erythrocyte aging, actual influx of creatine into erythrocytes and creatine contents in erythrocytes were measured by using method of high performance liquid chromatography and isotopic estimation of 14C-creatine concentration. Actual influx of creatine into erythrocytes was showed rapidly, in spite of constant contents of erythrocyte creatine under the condition to be incubated at 37 degrees C for approximate 4 hours in isotonic saline containing high concentration of creatine. Km values of the creatine uptake into young erythrocytes were evidently smaller than that into old erythrocytes. On the other hand, no significant difference of Vmax values was observed to be dependent on erythrocyte aging. PMID- 1593771 TI - [Endosonographic diagnosis of metastatic tumors in the recto-uterine or recto vesical space by transrectal scan]. AB - A 6-year experience of transrectal ultrasonography (TRUS) in 75 patients with advanced gastrointestinal cancers was reviewed regarding the diagnostic yield of metastatic extrarectal tumors. A diagnostic capability of TRUS (a sensitivity of 82.9%, a specificity of 97.5% and an accuracy of 90.7%) was statistically superior to that of digital rectal examination (a sensitivity of 62.9%, a specificity of 75% and an accuracy of 69.3%). However, TRUS could hardly correctly diagnose a miliary type of extrarectal tumors in contrast to nodular and thickened types. TRUS also had an advantage over conventional ultrasonography in detecting a small amount of ascites with a sensitivity of 75%, a specificity of 93% and an accuracy of 86.6%. Patients with positive signs of extrarectal tumors or ascites on TRUS survived significantly shorter than those with negative signs. TRUS renders a convenient means in the objective diagnosis of peritoneal carcinomatosis, and predicts patient's prognosis. PMID- 1593772 TI - [The immunohistochemical study on the recurrent mechanism of acetic acid induced gastric ulcer in rats--extracellular matrix and cellular kinetics]. AB - The localization of fibronectin (FN) and laminin (LM) and cellular kinetics of epithelium in acetic acid induced gastric ulcers were examined by immunohistochemistry, comparing fundic glands ulcer with fundic-pyloric border ulcer. Ulcers on fundic glands had become scars in 30 days and didn't relapse after that. More than half of ulcer on fundic-pyloric border changed into scar in 30 days, however, they started to recur at about 45 days. The localization of LM was observed on basement membrane (BM) beneath epithelia, blood vessel walls and musculature. The percentage change in intra-blood-vessel area compared to total area was analyzed by immunohistochemical distribution of LM. As for ulcer on fundic glands, the percentage of intra-blood-vessel returned to normal numbers after healing to scars (30 days). On the other hand, the percentage of intra blood-vessel of ulcer on fundic-pyloric border after changing into scar (30 days) and recurring (45 days) significantly increased compared with initial healing (10 days, 20 days). The stratum of spindly cells with FN-positive surface appeared under regenerative epithelia of ulcers on fundic-pyloric border from 10 days to 20 days. This part was proven to be spare in blood vessels by distribution of LM. Though this stratum was not observed at every stages after recurrence, the collagen fibers of ulcer on fundic-pyloric border had got mature thickly. These results may lead the following theory; the phenomenon that the distribution of blood supply in stomach seems to be more dominant in submucosal fibrous layer than in mucosa may cause the recurrence of fundic-pyloric border ulcers. The cell number of S-phase was significantly more numerously observed in relapsed ulcer on fundic-pyloric border than in pre-relapsed one (10 day). The cell number of S phase on fundic gland ulcer tended to decrease after healing to scar stage. The immediate restoration of connective tissue under the mucosa is considered to promote epithelial cellular kinetics in recovering and maturing. PMID- 1593773 TI - [Bio- and histochemical changes of tissue kallikrein in the rat stomach after water immersion-induced gastric ulcer]. AB - The posterior stomach was isolated from each male Donryu rat and separated into two parts: the tunicae mucosa and submucosa and the tunicae muscularis and serosa. Active and inactive tissue kallikrein were measured using sandwich type enzyme linked immunosorbent assay (s-ELISA) and H-Pro-Phe-Arg-MCA to complement each other. Inactive tissue kallikrein was determined (1) by measuring total tissue kallikrein and active tissue kallikrein in trypsin-treated samples and trypsin-nontreated ones, respectively; and (2) by subtracting active tissue kallikrein from total tissue kallikrein. Although tissue kallikrein was not demonstrable in the tunicae muscularis and serosa, inactive tissue kallikrein in the tunicae mucosa and submucosa reached 79.6% with s-ELISA and 99.1% with H-Pro Phe-Arg-MCA. Water-immersion stress significantly decreased total tissue kallikrein at Stage IV of ulcers compared with the control value (p less than 0.001 in both measuring methods). Immunohistochemical staining was made using the avidin-biotin-horseradish peroxidase complex method. Tissue kallikrein was proved to be diffusely present as the inactive type within the epithelial cells of the pits in the gastric mucosa of the normal rats. With the progress of ulcers, however, it disappeared from the cells and appeared in the intercellular space. At Stage IV, it began to disappear even from the intercellular space. Based on the previously proposed process of tissue kallikrein release into blood in man, a possible interpretation of the above findings is that inactive tissue kallikrein may serve to maintain the gastric mucosa in a normal state; and that it may be transformed into the active type with ulceration and eliminated in a form of complex with some protease inhibitor in the course of aggravation. PMID- 1593774 TI - [Prevalence of HCV antibodies in Yatsuka town of Simane prefecture, Japan]. AB - To clarify the potential role for HCV in the development of chronic liver disease in Yatsuka town with a high morbidity of liver disease, epidemiological studies were taken in 459 subjects of Yatsuka town compared with 219 subjects of Mihonoseki town with a low one. In Yatsuka town, the mortality rate of liver cirrhosis was three times higher than the overall rate in Simane prefecture, and the rate of liver cancer rapidly increased in recent years. Age and sex-matched epidemiological studies showed a significantly higher incidence of hepatic dysfunction compared with Mihonoseki town (11.5% vs 3.7%, P less than 0.01). The prevalence of HCV antibody was significantly higher in Yatsuka town than Mihonoseki town (16.6% vs 3.7%, P less than 0.001), although there were no differences in frequencies of HBs antigen and habitual alcohol drinker between the two districts. These data strongly suggest that the high prevalence of HCV may be associated with the high morbidity of chronic liver disease, especially hepatocellular carcinoma in Yatsuka town. PMID- 1593775 TI - [Choleretic effects of taurine on experimentally-induced intrahepatic cholestasis]. AB - When a lymphokine, the cholestatic factor, is intravenously injected into rats through a mesenteric vein, remarkable reductions in bile flow and bile acid excretion are observed. However when taurine was injected with the cholestatic factor, the reduction in bile flow and bile acid excretion were significantly suppressed. Moreover, injection of taurine with cholestatic factor resulted in the decreases of both bile acid-dependent bile flow and vesicular transport but not bile acid-independent bile flow. Not significant choleretic effects were noted when taurine alone was administered to normal rats. PMID- 1593776 TI - [A study of the dynamics of gallbladder contraction in irritable bowel syndrome]. AB - We examined gallbladder motility function after intramuscular injection of caerulein (0.2 micrograms/kg) to the cases of irritable bowel syndrome (IBS) by using ultrasonography. We measured gallbladder area pre and after caerulein injection (0' 5' 10' 15' 20' 25' 30' 40' 50' 60') and calculated contraction rate of gallbladder in each time. We applied one way analysis of variance among the four groups [diarrhea group (N = 9), alternative group (N = 8), constipation group (N = 8), control group (N = 15)]. Gallbladder contraction rate was low in diarrhea group and high in constipation group (p less than 0.05). And then we classified gallbladder contraction pattern to three groups (hyperkinetic, intermediate, hypokinetic). These three groups correlated bowel habits and biliary knocked pain. Therefore, constipation group showed hyperkinetic tendency and diarrhea group showed hypokinetic tendency (chi 2 analysis: p = 0.004 CMH analysis: p = 0.001). And biliary knocked pain significantly appeared in constipation group and hyperkinetic type of gallbladder (chi 2 analysis: p = 0.026, CMH analysis: p = 0.019). Consequently, it was suggested that bowel habits concerned with abnormality of gallbladder motility function in IBS. PMID- 1593777 TI - [A case of minute remnant stomach cancer derived from gastritis cystica polyposa]. PMID- 1593778 TI - [Bleeding Meckel's diverticulum in a patient with Crohn's disease]. PMID- 1593779 TI - [A case of ileal carcinoid tumor penetrating mesocolon with asthma attack]. PMID- 1593780 TI - [A case of hepatic amyloidosis with hepatic failure]. PMID- 1593781 TI - [A case of hypervascular polypoid lesion of the gallbladder]. PMID- 1593782 TI - [A case of chronic pancreatitis which was difficult to be differentiated from small pancreatic tumor]. PMID- 1593783 TI - [A trial of peroral cholecystoscopy after dilatation by balloon in the cystic duct]. PMID- 1593784 TI - [The pathology and treatment of incontinence]. AB - In order to understand the pathology of incontinence, it is important to investigate urinary symptoms, urological and neurological examinations and urodynamics. There are two kinds of incontinence. One is true incontinence in which urine passes through urethra, and the other is false incontinence due to the ectopic opening of the ureter, for example to the vagina. The former includes stress incontinence, urge incontinence, reflex incontinence, overflow incontinence and total incontinence. Stress incontinence occurs with the sudden increase of abdominal pressure such as cough, running and exertion. The cause of stress incontinence is thought to be weakening of pelvic floor muscles after delivery or aging. In these patients, the bladder base and urethra move downwards and backwards, which make the posterior vesico-urethral angle more than 120 degrees. Treatment of stress incontinence includes pelvic floor exercise, administration of alpha-stimulants which increase the tonus of the internal sphincter and surgery to elevate the urethra. Urge incontinence is observed when detrusor instability occurs. It is also seen in patients with neurological diseases such as multiple cerebral infarction or with benign prostatic hypertrophy (BPH). Treatment of urge incontinence includes administration of anticholinergics to decrease bladder hyperreflexia. Reflex incontinence is seen in patients with spinal cord disorders. It occurs due to reflex contraction of detrusor and the treatment involves administration of anti-cholinergics. Overflow incontinence is seen in patients with voiding difficulties due to BPH. It occurs when residual urine increases and when the intravesical pressure exceeds urethral pressure on body movement. Treatment for this is intended to improve voiding difficulties. Total incontinence occurs when total sphincter function is damaged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593785 TI - [The disturbance of lipid metabolism in the elderly]. PMID- 1593786 TI - [Hyperbilirubinemia associated with sepsis in the elderly]. AB - In order to elucidate the frequency of hyperbilirubinemia associated with sepsis in the elderly, as well as in clinical and histological characteristics, a total of 117 autopsy cases with sepsis were analyzed retrospectively. Based on the clinico-pathological findings, 48 cases with primary hepato-biliary, cardiac, hematological and shock complications, were excluded because these disorders were thought to affect liver function tests. Four cases out of the remaining 69 cases, 5.8% of the total, showed hyperbilirubinemia above 2 mg/dl (average 4.1 mg/dl), which was thought to be associated with sepsis itself. In these 4 cases, disproportionately high levels of blood total bilirubin were characteristic compared to changes of GOT, GPT, LDH, ALP and gamma-GTP levels. Blood culture of these 4 cases revealed Gram-negative organisms in 3 cases and Gram-positive in 1 case. Histological findings of the liver included cholestasis, Kupffer cell hyperplasia and cell infiltration in the sinusoid and portal areas, however these findings were mild and nonspecific. It is important to recognize the presence of hyperbilirubinemia associated with sepsis in order to properly treat febrile elderly patients with hyperbilirubinemia. PMID- 1593787 TI - [Depressed mood and subjective sensation well-being in the elderly living alone on Oki island in Shimane prefecture]. AB - In order to clarify the influence of living alone on depressed mood and subjective sensation of well-being in the elderly, we studied 113 elderly (60 years old or more) living in Chibu village on Oki island. The subjects were divided into two groups, 33 subjects (Single group) who were living alone (mean age 74.1 years) and 80 subjects (Married group) who were married and lived with their spouses (mean age 69.0 years). For the measurement of depressed mood and subjective sensation of well-being the Zung Self-Rating Depression Scale (SDS) and Morale Scale were used. The SDS score of the Single group was significantly higher than that of the Married group. The incidence of depression was higher in the Single group than in the Married group, but the difference was not of statistical significance. The Morale Scale score in the Single group was significantly higher than in the Married group. Subjects in the Single group felt more lonely than those in the Married group, but not significantly so. There was a highly significant correlation between the SDS score and the Morale scale score. We concluded that, in the elderly, living alone is more depressing and less satisfying than living with a partner. PMID- 1593788 TI - [Age-related effects of gastroduodenoscopy on arterial oxygen saturation]. AB - Although endoscopy is widely used for safe and accurate examinations of gastroduodenal disease cases, several investigators reported arterial oxygen desaturation occurring during endoscopy. Endoscopy-induced oxygen desaturation is hazardous because it increases the risk of cardiac arrhythmia. This study is designed to investigate whether gastroduodenal endoscopy causes remarkable oxygen desaturation in elderly patients in comparison with younger ones and to study whether nasal oxygen administration can prevent it. Forty-four patients over 61 years old and 37 patients younger than 60 were divided into two groups, to one of which 100% oxygen (2 l/min) was administered through nasal prongs. During endoscopy, blood pressure, pulse rate, and arterial oxygen saturation (SaO2) were recorded at one-minute intervals by a pulse oximeter. Intubation of the endoscope caused a transient drop in oxygen saturation both younger and older patients with greater drops in older subjects (1.7 +/- 0.4% in the young and 3.3 +/- 0.8% in the old groups). In the older groups, two out of 20 patients who had no oxygen administration showed a saturation decrease of over 7%. On the other hand, no younger subject showed such a large degree of oxygen desaturation. Oxygen administration effectively prevented the endoscopy-induced desaturation both in younger and in older patients. In summary, the results of this study suggested that older subjects had a greater decrease of oxygen saturation during gastroduodenofiberscopy and that oxygen administration is useful to prevent the endoscopy-induced desaturation. PMID- 1593789 TI - [MR study of the brain stem in elderly subjects]. AB - Findings in patients in whom brain stem lesions were suspected were studied by a high-field-strength (1.5 T) MR imager. MR scans were obtained in 97 patients over a 10-month period. The mean age was 71 years (range, 39-94 years). A high incidence of infarction and lesions showing a high signal on T2-weighted image, but an almost normal signal on the T1-weighted image were observed at the pons in elderly cases. Furthermore, cases in which these two findings were observed, had a high incidence of lesion at other regions than pons. Cases with a past history of hypertension had higher incidence of lesions at the pons than normotensive patients (alpha less than 0.01). These findings suggest that MRI examination in the elderly could detect a high incidence abnormal lesions at the brain stem as well as in basal ganglia. PMID- 1593790 TI - [A case report of severe urinary retention and meteorism during flunarizine administration]. AB - A case of flunarizine hydrochloride (FZ)-induced severe urinary retention and meteorism which resulted from sphincter spasm of the urinary bladder and the anus is presented. An 81-year-old female had received 10 mg/day FZ orally for 12 months before hypokinesia and general fatigue developed. Physical examination revealed slight rigidity of the extremities, abdominal distention and spasm of the anal sphincter muscle. Laboratory examinations showed uremia (BUN 88 mg/dl, Creatinine 16.8 mg/dl) and abdominal X-ray demonstrated marked distention of the small and large bowels. Renal failure improved within 2 days after massive urination using a urethral catheter. Abdominal distention was improved by the ileus and anal tubes. The difficulties of urination and defecation and decreased mobility of the extremities were resolved one month after the cessation of FZ. No organic changes were detected in urinary, intestinal and neurological systems by cystoscopy, CT, MRI and gastrointestinal fiberscopy. Serum concentration of FZ was 42.5 ng/ml on admission but decreased slowly to 17.9 ng/ml 80 days later. Serum half life was calculated to be 55 days which was 3 times longer than that healthy younger volunteers. PMID- 1593791 TI - [A case of complete recanalization in the lower abdominal aorta by intraaortic infusion of a thrombolytic agent]. AB - Intraarterial infusion of thrombolytic agent is useful in the treatment of obstructive arterial diseases in various vessels. However, few studies have shown that this treatment is useful for aortic occlusion. We report the case with complete recanalization in the lower abdominal aorta following intraaortic infusion of a thrombolytic agent. A 59-year-old man was admitted because of weakness and pain in the bilateral lower limbs at rest. Aortography showed complete occlusion of the abdominal aorta proximal to the inferior mesenteric artery. Both external arteries were supplied via rich collaterals. He was treated by intraaortic urokinase infusion of 2,100,000 units. Total recanalization in the abdominal aorta and both common iliac arteries was obtained. Intraaortic infusion of urokinase was shown to be effective treatment of occlusion in the abdominal aorta. PMID- 1593792 TI - Effects of excess factor D on early- and late-phase activation of the complement cascade. AB - The present study was undertaken to examine the effects of excess factor D build up in the body of end-stage renal disease (ESRD) patients upon the activation of the alternative pathway and the terminal pathway in the fluid phase. First, to clarify the effect of excess factor D on the alternative pathway, purified factor D from an ESRD patient was added to normal serum and the changes in concentrations of C3a-des-Arg and C5a-des-Arg were investigated. The results showed that once the serum factor D level reached a concentration corresponding to 15 micrograms/ml in the serum of the ESRD patient, the C3a-des-Arg and C5a-des Arg levels had climbed to about 1.7-fold the concentration in normal serum. Next, in order to clarify the effect of excess factor D on the terminal pathway, purified factor D was added to normal serum, and the changes in C5b6 generation were examined. The results indicated that as the factor D level increased in the serum, the C5b6 level rose gradually also; and when the factor D concentration reached 15 micrograms/ml, the C5b6 generation had risen to approximately 1.5-fold the level in normal serum. The present results therefore suggest that factor D build-up in ESRD patients provides a uremic toxin that can cause abnormal activation of the whole complement cascade. PMID- 1593793 TI - Effects of cytokines on the growth of cultured rabbit renal cortical tubular cells. AB - The effects of various cytokines including interleukin-1 beta, -2, and -6, tumor necrosis factor-alpha, and granulocyte-macrophage colony stimulating factor on the DNA synthesis of cultured rabbit renal cortical tubular cells were investigated. Among these cytokines, it was found that only interleukin-1 beta could stimulate the DNA synthesis of cultured renal tubular cells, while interleukin-6 mildly suppressed the DNA synthesis of such cells. Interleukin-1 beta and -6 are produced by mesangial cells. The above results suggest that these cytokines may regulate the growth of tubular cells via the urinary flow in the nephron. PMID- 1593794 TI - Age-related character of glomerular lesions in IgA nephritis. (2). Histopathological peculiarity in childhood onset. AB - Histopathological analysis was performed in the first renal biopsy specimens of patients over and under 10 yrs of IgA nephritis. They were divided clinically into two groups, the one with remission and the other with prolonged disease state respectively. Increased mesangial sclerosis, frequent occurrence of segmental glomerular lesions and tubulointerstitial change were significantly evident in the group with prolonged disease state. It is suggested that similar glomerular events are progressing in IgA nephritis which is carried over to adult age. PMID- 1593795 TI - Stereoscopic study of renal proximal tubular basement membrane by quick-freezing and deep-etching method. AB - Rat kidney tissue was quickly frozen, fractured and deeply etched. A replica was prepared by shadowing with platinum and carbon. The proximal tubular basement membrane was found to be different from that in conventional ultrathin sections. The lamina lucida was not electron translucent but filled with a traversing filamentous structure, which connected the tubular cell membranes with the lamina densa. The lamina densa had a three-dimensional polygonal meshwork structure. This meshwork was composed of fibrils (6-9 nm in thickness). In the lamina reticularis, collagen fibrils and micro-threads formed a loose network structure. The traversing filamentous structure in the lamina lucida might serve as an anchorage for the cell membranes and extracellular matrices. PMID- 1593796 TI - Significance of deposits and abnormalities of the glomerular basement membrane in tissue injury accompanying IgA nephropathy. AB - The glomerular injuries in 129 cases of IgA nephropathy (IgA-N) were examined ultrastructurally with special reference to the glomerular basement membrane (GBM) deposits and capillary loop abnormalities, and the correlation between these findings and the clinicopathological data was analyzed. The following results were obtained. 1) The degree of daily excretion of urine protein (UP) and creatinine clearance (Ccr) revealed a significant correlation with the degree of mesangial hypercellularities and the frequency of segmental lesions. 2) All sites of GBM deposits, and discontinuity and/or splitting among the GBM abnormalities showed a significant relation to the severity of proliferation and segmental lesions. 3) The GBM deposits, discontinuity and splitting showed a significant relation to the degree of UP and Ccr. We speculate therefore that capillary loop deposits and/or capillary loop discontinuity and splitting could represent histological prognostic factors for an unfavorable outcome in IgA nephropathy. PMID- 1593797 TI - Study on the relation between renal tubular disorders and glomerular dysfunction in the early phase of insulin-dependent diabetes mellitus in children. AB - To study the relations between renal tubular disorder and glomerular dysfunction in the early phase of insulin-dependent diabetes mellitus (IDDM), we performed concomitant measurements of urinary beta-D-N-acetyl glucosaminidase (NAG), beta 2 microglobulin (BMG), and microalbumin in 29 of pediatric patients with IDDM, 15 normal controls, and 83 patients with non-diabetic ketoacidosis. Urinary NAG levels were significantly elevated in the IDDM patients compared with controls. Urinary BMG levels were also elevated in IDDM, however, they were not as prominent as NAG levels. Although urinary microalbumin levels were elevated in the IDDM patients, statistical analysis did not show any significant difference between the IDDM patients and controls. Urinary NAG and BMG concentrations were also increased in patients with non-diabetic ketoacidosis, suggesting a toxic effect of ketone bodies to renal tubular cells. Statistically significant correlations were noted both between urinary NAG and microalbumin and between urinary BMG and microalbumin. These results suggest that, in early phase of IDDM, microalbuminuria is preceded by elevations in urinary NAG and BMG levels, and that keton bodies have deleterious effects on renal tubular cells. PMID- 1593798 TI - Early morphological changes of tubules in rats with chronic renal failure. AB - We investigated the early changes of tubules and effect of the oral adsorbent, AST-120, on the early changes of tubules in rats with chronic renal failure. Sprague-Dawley rats were divided into two groups with and without AST-120, after 3/4 nephrectomy. Although there were no significant differences in levels of blood urea nitrogen, serum creatinine, creatinine clearance, inulin clearance, para-aminohippuric acid clearance and urinary N-acetyl-beta-D-glucosaminidase at week 8 between the two groups, the amount of 24-hour urinary protein excretion and the direct systolic blood pressure at week 8 were significantly decreased in the group with AST-120. Examinations by light microscopy at week 8 revealed that proteinaceous casts in the tubules, tubular dilatation and infiltration of monocytes into the interstitium in the group with AST-120 were less prominent than those in the group without AST-120. A significant difference in numbers of proteinaceous casts was noted at week 8 between the two groups. In rats with chronic renal failure at the early stage, it is concluded that the formation of proteinaceous casts, resulting in tubular damage, is increased and that AST-120 delays the occurrence of proteinaceous casts by delaying the increase in urinary protein excretion. PMID- 1593799 TI - Evaluation of parameters for adequate dialysis therapy: (2). Comparison between parameters according to UKM and other laboratory data. AB - Urea kinetic modeling (UKM) is often regarded as the best method for assessing the dialysis adequacy and consequently for the prescription of treatment time. However, other parameters are involved in the monitoring of end stage renal disease (ESRD) patients. Kt/V-urea and protein catabolic rate (pcr) were evaluated in 53 ESRD patients (25 males and 28 females; mean age, 60 +/- 2 years old; mean duration, 80 +/- 11 months), twice at an interval of 4 months, and pre dialysis concentration of (pre-DC) plasma potassium, bicarbonate, calcium and phosphate were measured. The pre-dialysis systolic blood pressure and hematocrit were also recorded. The numbers of patients who were within the optimal range of Kt/V-urea and pcr recommended by Gotch and Sargent were 36 (67.9%) and 39 (73.6%), respectively, at the first control period, and 39 (73.6%) and 44 (83.0%) at the second control period. However, only about 50% of the patients were within the optimal range of pre-DC plasma calcium, phosphate and bicarbonate. Furthermore, very few patients fulfilled the conditions for all the parameters. It is concluded that (1) UKM is required to describe the domain of dialysis prescription, and (2) other parameters which are not dependent so much on dialysis should be taken into account for assessing the adequacy of dialysis. PMID- 1593800 TI - Alterations in sex hormones and sexual function of patients with renal failure treated with recombinant human erythropoietin. AB - Since it has been reported that correction of anemia in long-term hemodialysis patients by using human recombinant erythropoietin (r-HuEPO) is associated with improve sexual function, we conducted the present study to evaluate the changes in sex hormones as well as sexual function after r-HuEPO administration (1500 to 4500 IU per dialysis) for a year in patients on regular hemodialysis. Thirteen patients receiving regular hemodialysis entered this study. Their median age was 43 years. Along with correction of anemia (the hematocrit increased from 20 to 28%), testosterone (T) increased from 2.4 +/- 0.1 to 2.6 +/- 0.2 ng/ml, follicular stimulating hormone (FSH) increased (29 +/- 5 to 73 +/- 7 mIU/ml), luteinizing hormone increased (69 +/- 14 to 160 +/- 21 IU/ml) and prolactin decreased (all changes are significant at p less than 0.05). However, the improvement of sexual function was not remarkable. Only 25% of the uremic patients treated with r-HuEPO showed amelioration of this function. From the present data, it does not seem likely that therapy with r-HuEPO induces directly amelioration of sexual function through changes in sex hormones. PMID- 1593801 TI - Diagnostic significance of urinary sialic acid in diabetic nephropathy. AB - The diagnostic significance of urinary sialic acid (SA) determinations was evaluated in relation to the histological findings of renal biopsy specimens. The subjects enrolled in this study comprised 82 diabetics. They were divided into 4 groups according to Gellman's criteria, namely D0, DI, DII and DIII approximately IV. Thirty non-diabetic healthy volunteers were used as controls. The urinary SA was measured by high performance liquid chromatography, and the urinary albumin excretion was estimated by solid phase radioimmunoassay. In addition, urine samples were assayed for N-acetyl-beta-D-glucosaminidase (NAG) and beta 2 microglobulin (beta 2MG). The urinary level of total SA (under conditions of hydrolysis) was significantly increased in the DII and DIII approximately IV groups as compared to the controls; however, a similar value was observed in the D0, DI and control groups. The urinary level of glycoprotein-bound SA was significantly increased in all diabetics as compared to the control group, and was significantly higher in the DII and DIII approximately IV groups than in the D0 and DI groups. The bound-SA/total-SA ratio (B/T ratio) showed a significant increase with respect to the progress of diffuse lesions. A weak correlation was noted between the B/T ratio and urinary protein excretion. However, there was no correlation between the B/T ratio and other indices. The urinary SA is considered to represent a useful indicator for estimating diabetic nephropathy. PMID- 1593802 TI - Extracellular matrix protein: gene expression and synthesis in cultured rat mesangial cells. AB - Production of extracellular matrix (ECM) by mesangial cells (MCs) contributes to progressive glomerulosclerosis. Our previous immunocytochemical studies on ECM production by MCs [1] were extended by examining the gene expression and protein synthesis using Northern blotting and ELISA. ELISA demonstrated that fetal calf serum (FCS) stimulated the synthesis of collagen I (CI), III (CIII) and IV (CIV), and laminin (LM). At and after confluence, the amounts of CIII, CIV and LM per DNA amount began to decrease, whereas that of CI did not. Northern blotting indicated that the mRNA expressions for CIV and LM were transiently increased by FCS. The mRNA expressions for CI and CIII decreased until confluence and then returned to the initial levels. These results suggest that FCS and cellular confluence affected the synthesis of ECM at both the level of gene expression and protein synthesis. The mRNA expressions for CIV and LM paralleled the protein synthesis and appeared tightly regulated. CI and CIII synthesis and mRNA expression were not coordinate and were not regulated in the same manner as the basement membrane matrix components. PMID- 1593803 TI - A case of pseudoaldosteronism induced by glycyrrhizin. AB - A 55-year-old man was referred to us for evaluation of hypertension and hypokalemia. He had been administered glycyrrhizin from one year before admission for the treatment of chronic hepatitis. On admission, his blood pressure was 230/105 mmHg; serum potassium, 2.4 mEq/l; the plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were undetectable. His blood pressure, potassium, PRA and PAC returned to normal within about 4 weeks after discontinuation of the glycyrrhizin. Re-administration of glycyrrhizin caused increases in PRA and PAC. His urinary cortisol excretion was increased and urinary cortisone excretion decreased, while his serum cortisol level remained unchanged. Supplementation of dexamethasone led to a decrease in blood pressure, and increased levels of serum potassium, PRA, and PAC. These results suggest that increased renal cortisol as a result of decreased conversion to cortisone might play an important role in the development of pseudoaldosteronism as well as in its own mineralocorticoid activity. PMID- 1593804 TI - [Study on cases of resected primary lung cancer in young persons]. AB - A clinical study was conducted of 17 patients aged less than 40 years who received resection for lung cancer in our department. The 17 cases made up 1.8% of the total series of 924 resected lung cancer cases, with the number of cases increasing as the age of 40 years was approached. The male-female ratio was 1.1:1, with proportion of women higher than in the total series of lung cancer cases. The histological type of included a high proportion of adenocarcinomas (47.0%), while squamous cell carcinomas were few. In addition, the proportion of tumors of low-grade malignancy such as carcinoid tumors and mucoepidermoid carcinomas was high. The majority (58.8%) of cases were detected by mass screening. As a result, the number of stage I cases was high (10 cases, 58.8%), and curative resection could be performed in 70.8%. The prognosis of these young patients did not differ significantly from that of the total resected group, with a 5-year survival rate of 62.4% achieved. It was considered that the prognosis of lung cancer in young persons can also be improved with early detection by mass screening and active surgical intervention. PMID- 1593805 TI - [Extended aortic reconstruction for dissecting aneurysm of the aorta]. AB - While lifesaving palliative surgery may be selected for dissecting aneurysm of the aorta, extended reconstructive surgery has been advocated as a more curative procedure. We performed a variety of extended reconstructive surgeries, for example, replacement of the ascending aorta and the aortic arch, subtotal replacement of the thoracic aorta, replacement of the entire descending thoracic aorta and replacement of the entire descending aorta in 20 cases of dissecting aneurysm of the aorta. However, the operative mortality remained high as 35%, and the operative procedures have not yet to be standardized. We believe that it is extremely important to strive for much greater improvement in the operative results by correct selection of the operative indications, and by improving the operative techniques and patient management during surgery. PMID- 1593806 TI - [Surgical treatment for lung cancer cases with an interlobar pleural involvement]. AB - Among surgically resected 192 lung cancer cases, eleven with a interlobar pleural involvement (p 3) were studied to clarify their characters. The five year survival rate of interlobar p 3 was 12.5% (15.6% in case of excluding death of other diseases), which was better than that of the other parietal p 3. Result of surgical treatment of lobectomy + partial resection for interlobar p 3 had better tendency compared with that of bilobectomy or pneumonectomy. But, unfortunately it was necessary for interlobar p 3 to care the local recurrence in the future. We hope that the general rule of the treatment for interlobar p 3 was carefully discussed furthermore, including the safety margin in the partial resection or the classification on T factor. PMID- 1593807 TI - [Surgical techniques of ventricular assist device]. AB - Since October 1982 to April 1990, we had 16 ventricular assist device (VAD) cases in our institute. Using this VAD system that was produced by Nippon Zeon company, surgical techniques for cannulation and de-cannulation could be made very easily, and connection between cannulae and pump also could be performed quickly. In this article, the actual surgical techniques and the know-how were illustrated in detail. If this techniques can be more accustomed, the clinical results of VAD cases will be improved. PMID- 1593808 TI - [Retro-TH catheter for retrograde coronary sinus perfusion]. AB - Retrograde coronary perfusion via the coronary sinus for myocardial protection can be performed more safely and exactly with Retro-TH catheter (3 way balloon catheter) which was originally designed. In addition, this catheter can be useful for selective cerebral perfusion in patients with aortic aneurysm involving aortic arch and for selective visceral and renal perfusion in patients with thoracoabdominal aneurysm. From January 1987 to March 1992, we performed 735 open heart surgery, 12 surgery for aortic arch aneurysm and 6 surgery for thoracoabdominal aneurysm with the aid of this catheter and obtained satisfactory results. PMID- 1593809 TI - [Clinical experience of sternal retractor for dissection of internal thoracic artery]. AB - We performed dissection of internal thoracic artery using sternal retracor for I.T.A. made by Delacroix Chevalier in France. This retractor composed of 5 elements i.e. arms, cranking axe, two assymetric claws and assymetric valve. This retractor is entirely reversible, so the same apparatus is used for left and light dissections. We concluded that this retractor has minimal risk to internal organs and the best position for exposure of I.T.A. PMID- 1593810 TI - [Aortic dissection associated with Turner's syndrome]. AB - We report two cases of Turner's syndrome who had had coarctation repair and who ultimately died from complications believed to be associated with Turner's stigmata. Case 1. The repair of coarctation of the aorta (Co/Ao) at age 5 was associated with the tear of the aortic wall and an Asc. Ao-Desc. Ao bypass together with the closure of the Ao proximal to the Co/Ao was performed. At age 10, she developed a dissecting aneurysm of the Asc. Ao seemingly unrelated to the previous surgery and the Asc. Ao was replaced by a prosthetic tube graft. Pathological diagnosis was cystic medionecrosis. The aortic valve was bicuspid. Subsequently, the patient showed progressive worsening of the aortic regurgitation. The aortic valve replacement at age 14 was complicated by significant bleeding and the patient died on the fifth postoperative day. Case 2. Co/Ao was repaired at age 8. During the operation, the aortic wall appeared to be thin and friable, and there was some tear of the posterior suture line which necessitated reanastomosis with resultant stenosis. At age 9, stenotic area was enlarged by an onlay-patch of a piece of woven Dacron arterial graft. There was gradual swelling of that area on routine x-ray examinations and an aortography at age 16 showed definite aneurysm formation. At age 18, she suddenly developed hemoptysis. Rupture of the aneurysm into the pleural cavity and the left lung was suspected. An emergency surgery to stop bleeding under hypothermic cardiopulmonary bypass was unsuccessful and the patient died in OR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593811 TI - [Selective jugular cannulation for hypothermic retrograde cerebral perfusion in thoracic aortic operations (reverse over the wire-catheter method)]. AB - We have employed hypothermic retrograde total body perfusion via the caval cannulae as a supportive measures to protect the brain and other systemic organs in operations for aortic arch aneurysms or acute aortic dissection. But occasionally unsatisfactory results ensued, because competent valves located in the internal jugular vein near the jugulo-subclavian junction may block retrograde blood flow to the brain from the caval cannula. To cope with this problem, we designed an easy and safe method to cannulate the internal jugular vein transatrially utilizing guidewire and central venous catheter, and thereafter we have used this technique clinically and obtained good results. PMID- 1593812 TI - [Staged sternal closure for the case of postoperative severe cardiac failure: a convenient method in the intensive care unit]. AB - A convenient method of staged sternal closure in the intensive care unit for a patient with severe cardiac failure was reported. According to the patient's cardiac function, optimal intersternal space can be adjusted. When using this method on a infant, the adjustment has shown to be very easy and take only a short time. However we have no experience on adults with stronger sternum. PMID- 1593813 TI - [Chest wall reconstruction with a prosthetic material molded from a extirpated specimen]. AB - A new molding technique of the Acryl-resin Marlex-mesh sandwich method is described. After the wide extirpation of the chest wall, the defect size tends to grow up more larger than the specimen. For making a just fit size prosthesis, we cut off a cardboard as the same size as the specimen and the Acryl-resin Marlex sandwich is molded from the cardboard. Other some know-how are in the text. PMID- 1593814 TI - [Two cases of congenital cardiac anomaly associated with esophageal atresia]. AB - Two cases of congenital cardiac anomaly associated with esophageal atresia and tracheo-esophageal fistula were presented. One case was HLHS, and the other was TAPVR. Esophageal procedures were performed earlier than cardiac procedures in both cases. Primary anastomosis for esophageal atresia just after birth in the latter case. Corrective procedures for cardiac anomalies were performed at 36 days and 35 days after birth, respectively. The HLHS case died perioperatively and the TAPVR case survived the operation and is alive one year postoperatively. PMID- 1593815 TI - [Two cases of severe ischemic mitral regurgitation treated with CABG alone]. AB - We report here two cases in which patients fell into pulmonary edema due to ischemic mitral regurgitation (ischemic MR) after cardiac catheterization and underwent emergency coronary artery bypass grafting (CABG) using an intra-aortic balloon pumping. The patient were a 65-year-old man and a 80-year-old woman, and both had a chief complaint of angina after myocardiac infarction. In both cases, coronary angiography revealed triple vessel disease, and left ventriculography showed severe MR. However echocardiography, when they were hospitalized, did not show significant MR. Therefore we thought that they had gone into congestive heart failure because cardiac ischemia and volume load following cardiac catheterization provoked MR. In fact, postoperative left ventriculography and echocardiography showed decreased MR. We now think that it is important to keep in mind the cases of severe ischemic MR for which CABG alone is adequate treatment and to evaluate ischemic MR not only by left ventriculography but also by echocardiography. PMID- 1593816 TI - [A case report of poststernotomy mediastinitis treated with the pectoralis major muscle flap after protracted wound irrigation]. AB - A 8-year-old boy developed mediastinitis after direct closure of atrial septal defect. Methicillin-resistant Staphylococcus aureus (MRSA) was detected from the wound. Intermittent wound irrigation with povidone-iodine solution and vancomycin solution was protracted for two months. After the remission of MRSA infection, implantation of pectoralis major muscle flap was performed. Without recurrence of infection the wound was healed completely. Although pectoralis major muscle flap is an effective method of choice for mediastinitis, an appropriate timing of enforcing this method should be investigated hereafter. PMID- 1593817 TI - [A case of schwannoma of the intrathoracic vagus nerve]. AB - A 42-year-old female was noted to have a mediastinal mass on routine chest roentgenogram. She was asymptomatic and physical examination was unremarkable. Computed tomography of the chest confirmed the presence of a 3.5 cm well circumscribed mass in the middle mediastinum adjacent to the aortic arch. Operation was performed. A solitary middle mediastinal tumor was readily apparent at the aortic arch to the left subclavian artery, originating from the vagus nerve superior to the take-off of the recurrent laryngeal nerve. Excision was possible by enucleation of the mass. The postoperative period was uneventful, although there was paralysis of the left vocal cord as evidenced by hoarseness. Histologically the diagnosis of a schwannoma of the vagus nerve was made. PMID- 1593818 TI - [A case of successful emergency coronary artery bypass grafting surgery for failed coronary angioplasty using percutaneous cardiopulmonary support]. AB - This is the first Japanese case of the successful emergency coronary artery bypass grafting (CABG) surgery for failed percutaneous transluminal coronary angioplasty (PTCA) using percutaneous cardiopulmonary support (PCPS). A 81-year old woman with old myocardial infarction and angina pectoris is presented. Her coronary angiogram showed the 90% and 50% stenosis of the right coronary artery (RCA) and the total occlusion of the left anterior descending artery (LAD). PTCA for the 90% stenosis of RCA was performed. But, during the balloon dilation, her heart rate and blood pressure decreased. PTCA was stopped. As her chest pain was worse, re-PTCA was tried, using PCPS. Under PCPS (3 l/min), the balloon dilation was performed safely and smoothly. But, the unexpected dissection of RCA occurred, and became larger rapidly. After 85 minutes, the emergency CABG was performed. By using PCPS, the stable hemodynamics was given till the operation. CABG to RCA and LAD was performed safely. After the surgery, the patient progressed well. PCPS was a very useful cardiopulmonary assist device. PMID- 1593819 TI - [Right-sided patent ductus arteriosus with a right aortic arch and right descending aorta]. AB - We experienced an extremely rare anomaly, i.e. right-sided persistent ductus arteriosus with a right aortic arch and right descending aorta. Reviewing the literature, we found only two cases clinically reported in Japan as far as we know. The diagnosis was established by angiography and MRI. We treated the patient successfully through right thoracotomy. PMID- 1593821 TI - [A case of supravalvular pulmonary stenosis associated with Noonan's syndrome: usefulness of Doty's operation]. AB - A twelve-year-old boy associated with Noonan's syndrome is reported. He had supravalvular pulmonary stenosis with a very high right-ventricular pressure, higher than that of systemic. Surgical treatment was performed to the supravalvular pulmonary stenosis with the technique of Doty's operation for supravalvular aortic stenosis, brought an excellent results. The gradient between the right ventricle and the pulmonary artery fell from 97 mmHg to 30 mmHg. The residual gradient is caused by functional infundibular stenosis. Doty's operation is a useful method for the operation of severe supravalvular pulmonary stenosis, too. PMID- 1593820 TI - [A case of malignant lymphoma of anterior mediastinum requiring superior vena cava reconstruction]. AB - The patient was a 21-year-old female with malignant lymphoma of the anterior mediastinum, which was associated with superior vena cava (SVC) syndrome due to tumor invasion and tracheo-bronchial stenosis due to tumor compression. The bilateral brachio-cephalic vein and superior vena cava were resected with the tumor, and SVC reconstruction with a ringed expanded polytetrafluoroethylene (EPTFE) graft was performed between the right brachio-cephalic vein and SVC, and between the left brachio-cephalic vein and the right appendage. Postoperative anti-coagulant therapy was not performed. Postoperatively, SVC syndrome and the complaint of tracheo-bronchial stenosis disappeared promptly. Venography, which was performed 2 weeks postoperatively, presented patency between the right brachio-cephalic vein and SVC, but the graft between the left brachio-cephalic vein and the right appendage was obstructed. SVC reconstruction using a ringed EPTFE graft is considered to be significant for the improvement of resectability and the relief of clinical symptoms. PMID- 1593822 TI - [Acute aortic dissection complicating coronary artery bypass surgery]. AB - We experienced a patient in whom acute ascending aortic dissection appeared to develop at the site of injection of the cardioplegic solution during coronary artery bypass surgery. The patient was a woman aged 70, who was demonstrated to have calcification of the posterior wall of the ascending aorta by preoperative CT scanning. When dissection developed at the cardioplegia injection site after removal of the aortic cross clamp, the aorta was transected and teflon felt was applied to the aorta internally and externally before end-to-end anastomosis was performed. Postoperative CT scanning revealed closure of the dissecting lumen, and the patient was discharged from hospital on the 33rd postoperative day. PMID- 1593823 TI - [Cardiac strangulation with permanent epicardial pacemaker lead]. AB - A 3-year-old boy underwent corrective surgery for tetralogy of Fallot. During the operation, permanent epicardial pacemaker leads were implanted for complete A-V block, which was transient and a generator implantation was not necessary. The postoperative course was uneventful and he had been doing well until nine years of age, when he was admitted to our hospital with general fatigue. The data of echo cardiogram and cardiac catheterization showed the biventricular heart failure with right ventricular outflow tract obstruction (RVOTO). Because of his rapid deterioration refractory to the intensive medical therapy, semi-emergency surgery was recommended to relieve his RVOTO. It was found during the operation that the looped pacemaker leads had carved deeply in the atrioventricular groove, so that compressed the main pulmonary artery, left main coronary artery and encircled left ventricle. The pacemaker leads were dissected as long as possible, and cut segmentally. Additionally a patch enlargement of the main pulmonary artery was necessary to relieve the residual stenosis. Although IABP support was needed in a while, his postoperative course was uneventful, and postoperative examinations showed normal cardiac function. This rare complication, so called "cardiac strangulation", should be in mind when the implantation of permanent pacemaker leads is indicated in pediatric cases. PMID- 1593824 TI - [A case of simultaneous operation for ischemic heart disease and lung cancer]. AB - A case of 76-year-old man had a coin lesion in the chest roentgenogram, which rapidly grew with central necrosis, and chest pain at rest. Squamous cell carcinoma was concluded from transbronchial lung biopsy for that lesion. Coronary angiography revealed long segment occlusion of the left anterior descending which was not a candidate for percutaneous transluminal coronary angioplasty and 90% stenosis of the left circumflex coronary artery. Aorto-coronary bypass grafting and right upper lobectomy via midsternotomy, was simultaneously performed. the postoperative course was fair and there was no cardiac complication. A simultaneous operation is more preferable in selected cases. PMID- 1593826 TI - [Response criteria for urological cancer treatment]. PMID- 1593825 TI - [A case of pure unroofed coronary sinus syndrome with persistent left superior vena cava]. AB - A 36-year-old women with pure unroofed coronary sinus syndrome was reported. The anomalies of the cardiovascular system were absence of the coronary sinus, coronary sinus ASD and persistent left superior vena cava (PLSVC) draining into the left atrium. In this case, the PLSVC was ligated in the pericardium and the atrial septal defect was closed with a Dacron patch. There was no cerebral complication due to the increased intracranial pressure after ligation of the PLSVC. Postoperative coronary arteriography revealed absence of the coronary sinus in the venous phase. PMID- 1593827 TI - [Complications of Kock continent reservoir. Report of 103 cases]. AB - We installed a Kock continent reservoir in 103 patients after radical cystectomy or pelvic exenteration between Feb. 1986 and Dec. 1989. They consisted of 81 male and 22 female patients. Patients' age ranged from 30 to 78 years with the average being 63 years. Their original diseases were bladder cancer (96 patients), prostatic cancer (2), sigmoid colon cancer (2) and others (3), The Kock reservoir was made by the procedure described by D. G. Skinner et al. The mean operation time for reservoir creation was 220 minutes. In 99 patients with a Kock reservoir for more than 3 months, the capacity of the reservoir was 200-900 ml with the average being 490 ml and the frequency of self-catheterization was 4 to 6 times a day. Early complications occurred within 3 months in 27 (26%) patients. Complications directly related to the reservoir were urine leakage (5 patients), intestine reservoir fistula formation (3) and necrosis of the reservoir (1). Late complications occurred after 3 months in 25 (25%) patients. They consisted of difficulty of catheterization (9 patients), ureteral reflux from reservoir (2), hydronephrosis (8), abscess (4), metabolic acidosis (2) and others. The results indicated that this procedure is an appropriate urinary diversion since the quality of life in the patients with a Kock reservoir is better. However, after this procedure surgical complications were not infrequent. Therefore, this procedure should be performed in selected patients. PMID- 1593828 TI - ["Dismembered spiral flap pyeloplasty" for uretero-pelvic junction obstruction]. AB - We report a new operative technique for plastic correction of uretero-pelvic junction (UPJ) obstruction: dismembered spiral flap pyeloplasty. It is similar to the method described by Culp & DeWeerd in that a flap is made spirally but different in that UPJ is detached. Relatively a long and wide spiral (oblique) flap, the apex of which directs cranioventrally or craniodorsally, is made using the dilated pelvis. The apex of the flap is reflected downward and anastomosed to the split ureteral end. Because the flap is made obliquely, one side of the flap base is approximated to the opposite pelvic margin; this helps to make gradual funnelling of pelvio-ureteric transition. The method seems to be fit for cases with considerably long stenosis of UPJ and with the UPJ locating relatively close to the medial margin of the renal parenchyma. Seven of 26 pyeloplasties were done by this method in our institute, and all the 7 cases had satisfactory results. PMID- 1593829 TI - [Biochemical analysis of the external urethral sphincter of female rabbits]. AB - The proportion of fast and slow myosin molecules in external urethral sphincter (EUS) was studied. The contents of fast and slow myosin light chains in EUS from 6 female rabbits (Japanese White, 6-month-old) were estimated using two dimensional electrophoresis. The percentages of fast and slow myosin molecules were 54.5 +/- 14.9 and 46.0 +/- 14.9, respectively. It was thus shown that female rabbits EUS is composed of both fast and slow muscle fibers. The ratio of fast to slow myosins in female EUS was different from that in male EUS (fast myosin 90%). These results implicate that female and male EUS would be functionally distinct. PMID- 1593830 TI - [Pelvic floor muscle training as treatment of stress incontinence. The effectiveness of vaginal cones]. AB - Pelvic floor muscle training is the mainstream of the non-operative treatment for female stress urinary incontinence. However, in order to make this method effective, it is mandatory to learn how to correctly contract pelvic floor muscles. Thirty adult women suffering from mild stress incontinence were instructed to train their pelvic muscles using vaginal cones. They retained cones of increasing weight in the vagina by contracting pelvic floor for 15 minutes twice a day. Twenty-seven of 30 (90%) patients could complete the training in five weeks. Both incidence and degree of incontinence decreased significantly after the training. The subjective improvement rate (incontinence cured or decreased by 50%) was 70%. The cone weights which they could hold over one minute and the voluntary pelvic floor contractions measured with the perineometer increased significantly, which indicated strengthening of pelvic floor muscles. Vaginal cones have a shape similar to tampons and are accepted by Japanese women with little psychological resistance. This device helps the patients to understand how to contract pelvic floor muscles and to motivate them to continue training, thus contributing for the treatment of stress incontinence. PMID- 1593831 TI - [Fertility in patients after surgical repair of membranous urethral strictures associated with pelvic fractures]. AB - We evaluated fertility in fourteen patients after surgical repair of membranous urethral strictures associated with pelvic fractures. Eight patients were operated on using Badenoch's method (pull through) and six patients by end-to-end anastomosis of the urethra. All of them have maintained libido and potency after urethroplasty. No ejaculatory disturbance had ever occurred since surgery. Semen analysis was evaluated three months to four years after urethroplasty and serum hormone levels were measured in four patients. The results were as follows: 1) All except 2 patients had normal semen volume (more than 2 ml). 2) Nine patients (64%) had a sperm density of more than 40 x 10(6)/ml. Two patients had a sperm density of 20 to 40 x 10(6)/ml and three patients less than 20 x 10(6)/ml. 3) Nine patients (64%) had a sperm motility of more than 50%, three 30-50% and two less than 30%. 4) Seven patients (50%) had normal semen findings with a sperm density of more than 20 x 10(6)/ml and a sperm motility of more than 50% according to the WHO laboratory manual. 5) Pyospermia (WBC greater than or equal to 10/hpf) was observed in three patients. However, they never had subjective symptoms or objective findings of inflammation. 6) Serum LH, FSH, testosterone and PRL levels were within normal limits. 7) After urethroplasty, two patients married and their wives became pregnant. In conclusion, these results indicate that surgical repair of membranous urethral strictures associated with pelvic fractures has little effect on fertility. PMID- 1593832 TI - [Assessment of autonomic nervous function in impotence using sweat response induced by intradermal injection of acetylcholine]. AB - It is important to evaluate the autonomic nervous function which controls penile erection. One method utilizes intradermal injection of acetylcholine to produce localized sweat response. The sweat response depends on the peripheral autonomic nervous supply. Therefore, the response can be used to detect peripheral autonomic nervous dysfunction. We tried to evaluate the peripheral autonomic dysfunction in 29 impotence using a sweat spots test. We classified the 29 impotence into 6 groups with standard tests such as the papaverine test, nocturnal penile tumescence monitoring, recordings of bulbocavernous reflex, etc. The results were as follows: psychogenic IMP; 8, neurogenic IMP; 8, arterial insufficiency; 5, corporeal veno-occlusive insufficiency; 6 neurogenic with arterial insufficiency; 1, and neurogenic with corporeal veno-occlusive insufficiency; 1. The score of sweat spots test was 25.3 +/- 10.9, being in normal, nineteen severe in 3 and slightly abnormal in 7. Many cases of severe and slightly abnormal patients were DM patients classified into neurogenic IMP. We found 2 cases that were not detected by bulbocavernous reflex but found to be abnormal by sweat spots test. Therefore we conclude that this test effective to detect the autonomic nervous dysfunction in impotence. PMID- 1593833 TI - [Optimal dose of cyclosporin in living related kidney transplantation]. AB - We performed in total 528 kidney transplantations from Feb. 1983 to Dec. 1988 in Kidney Center of Tokyo Women's Medical College. Of the 528 kidney transplantations, 450 were living related kidney transplantations. The living related renal transplant recipients treated with CYA were divided into 3 groups: high dose CYA double drug therapy group (group 1), high dose CYA triple drug therapy group (group 2) and low dose CYA triple drug therapy group (group 3). Group 1 (n = 263) was treated with CYA (initial dose 12 mg/kg) and methylprednisolone (MP). Group 2 (n = 106) was treated with CYA (initial dose 10 mg/kg), MP and azathioprine (AZ) (1 mg/kg). Immunosuppression of group 3 (n = 81) consisted of CYA (initial dose 6 mg/kg), MP and AZ (2 mg/kg) (or mizoribine (MZ) (3-5 mg/kg). CYA serum trough level (polyclonal) was lowered according to the initial dose of CYA, and in particular trough level in group 3 was controlled at a low level (50-150 ng/ml in induction phase) to reduce CYA nephrotoxicity. However, even if strict control of serum trough level was accomplished, we could not get improvement of renal function in Group 3. Group 3 had more frequent and severe accelerated acute rejections (AAR) than the other groups. These data showed that inadequate immunosuppression in group 3 caused more frequent and severe rejection episodes. Also, renal biopsy revealed CYA nephrotoxicity even in group 3 and this nephrotoxicity may have been caused by ischemic damage by severe rejections.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593834 TI - [A case report: occurrence of bladder carcinoma in the defunctionalised bladder in a patient after operation of left ureteral carcinoma]. AB - An eighty year-old woman was diagnosed as left ureteral carcinoma and right dysfunctional kidney in 1984. Left partial ureterectomy, partial cystectomy, and left ureterocutaneostomy were performed and her bladder was left behind after the operation. In 1990 (72 months after the operation), she was aware of bleeding from the urethra. A bladder wash was performed, demonstrating malignant cells on cytological examination, and cystoscopy revealed a papillary tumor in the defunctionalized bladder. Total cystectomy was performed and the histological findings of the surgical specimen showed transitional cell carcinoma, grade 2, pTaNoMo. This case shows the need for periodic examinations of the defunctionalized bladder, because renal pelvic and ureteral carcinoma tends to recur in the bladder within two years after operation and because tumors rarely developed in the defunctionalized bladder. PMID- 1593835 TI - [Renal cell carcinoma with renal artery aneurysm treated by extracorporeal surgery and autotransplantation--a report of 2 cases]. AB - We experienced two cases of renal cell carcinoma with renal artery aneurysm in the contralateral kidney. These cases have not been reported in the literatures which we have so far explored. In our cases, firstly tumor was resected, and then extracorporeal surgery and autotransplantation were performed on the renal artery aneurysm of the opposite side. Their postoperative courses were uneventful. Only a few instances of extracorporeal surgery and autotransplantation for renal artery aneurysm in a solitary kidney have been reported in the literature. However, no report of a case treated by extracorporeal surgery and autotransplantation for renal artery aneurysm in the contralateral kidney after surgical treatment of renal cell carcinoma has been made. Regarding the treatment of renal artery aneurysm, extracorporeal surgery and autotransplantation appeared satisfactory in our experience. It was a safe and assured surgical procedure. We recommend extracorporeal surgery and autotransplantation for renal artery aneurysm when management in situ is considered difficult. PMID- 1593836 TI - Health-care reform: a 'consciously incremental approach'. PMID- 1593837 TI - Disposal of medical waste. PMID- 1593838 TI - The influence of a mammography unit in rural hospitals on obtaining mammograms. PMID- 1593839 TI - Reducing traffic-accident-related trauma among children. PMID- 1593841 TI - Nursing diagnosis: "the other side". PMID- 1593840 TI - Exercise echocardiography for diagnosing coronary artery disease. PMID- 1593842 TI - Nursing case management and nursing diagnosis. PMID- 1593843 TI - Nursing diagnosis as a management tool. PMID- 1593844 TI - Breast-feeding the smallest consumer. AB - Breast-feeding has numerous advantages, yet the trend to breast-feed is declining. Nurses, as well as patients, can benefit from increasing their knowledge base about breast-feeding. Nurses have an important role to play in supporting breast-feeding mothers with current research-based knowledge. More importantly, nurses also serve as patient advocates for the neonate. The use of appropriate nursing diagnoses may facilitate an optimal breast-feeding experience for our smallest consumer, the neonate. PMID- 1593845 TI - Elevated glucose stimulates TGF-beta gene expression and bioactivity in proximal tubule. AB - Our previous studies have demonstrated that raising ambient glucose from 100 to 450 mg/dl significantly inhibited the proliferation of mouse renal proximal tubule cells in culture. This effect was demonstrated after a latent period of 24 to 48 hours. Because transforming growth factor-beta (TGF-beta) inhibits cell proliferation in most epithelial cell lines, we hypothesized that the inhibitory effect of high glucose levels on cell proliferation may be mediated by TGF-beta. The present studies were performed to test the hypothesis that TGF-beta is an autocrine cytokine whose activity can be modulated by ambient glucose. Exogenous TGF-beta inhibited [3H]-thymidine incorporation in a dose-dependent fashion and with high affinity (picomolar range), but with slightly lower potency in high versus normal glucose media. Northern analysis of mRNA demonstrated that proximal tubule cells constitutively express TGF-beta 1 transcripts, and that the steady state level of TGF-beta 1 mRNA was, on average, 63% higher in the cells grown for 48 hours in high versus normal glucose media. Furthermore, the conditioned media of cells exposed to 450 mg/dl glucose exhibited endogenous TGF-beta bioactivity as measured by inhibition of cell proliferation. The addition of a rabbit antiporcine TGF-beta neutralizing antibody significantly increased basal thymidine incorporation in high glucose media to levels approaching those of cells grown in normal glucose media. In contrast, the anti-TGF-beta antibody did not have a significant effect on the growth of cells in the normal glucose media.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593846 TI - A monoclonal antibody against GBM heparan sulfate induces an acute selective proteinuria in rats. AB - After immunization of mice with partially-purified heparan sulfate proteoglycan (HSPG) isolated from rat glomeruli, a monoclonal antibody (mAb JM-403) was obtained, which was directed against heparan sulfate (HS), the glycosaminoglycan side chain of HSPG. In ELISA it reacted with isolated human glomerular basement membrane (GBM) HSPG, HS and hyaluronic acid, but not with the core protein of human GBM HSPG, and not with chondroitin sulfate A and C, dermatan sulfate, keratan sulfate and heparin. Furthermore, it did not bind to laminin, collagen type IV or fibronectin. Specificity of JM-403 for HS was also suggested by results of inhibition studies, which found that intact HSPG and HS, but not the core protein, inhibited the binding of JM-403 to HS. In indirect immunofluorescence on cryostat sections of rat kidney, a fine granular to linear staining of the GBM was observed, along with a variable staining of the other renal basement membranes. Pretreatment of the sections with heparitinase completely prevented the binding of mAb JM-403, whereas pretreatment with chondroitinase ABC or hyaluronidase had no effect. The precise binding site of mAb JM-403 was investigated by indirect immunoelectron microscopy. It revealed a diffuse staining of the whole width of the GBM. One hour after intravenous injection of JM-403 into rats, the mAb was detected along the glomerular capillary wall in a fine granular pattern, which shifted towards a more mesangial localization after 24 hours. No binding was observed anymore by day 15. Intravenous injection induced a dose-dependent, transient and selective proteinuria that was maximal immediately after the injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593847 TI - Vasoactive agents affect growth and protein synthesis of cultured rat mesangial cells. AB - Mesangial cell (MC) proliferation and extracellular matrix (ECM) formation are hallmarks of chronic glomerular disease. The present in vitro study examined the effects of the vasoactive agents angiotensin II (Ang II), arginine vasopressin (AVP), and serotonin (5-HT) on growth and protein biosynthesis of cultured rat MCs after 72 hours of incubation. AVP and 5-HT (10(-6) M) significantly increased DNA synthesis and growth of quiescent subconfluent MCs to levels of 25 and 45%, respectively, of the optimal stimulatory effect of 10% fetal calf serum (FCS) (both P less than 0.001). The mitogenic effect of Ang II was 10% of the 10% FCS effect (P less than 0.01). ECM production was studied by ELISA assay for fibronectin (FN) secreted into the culture medium (SeFN) and cell-associated FN, that is, intra- and pericellular FN (CaFN). In all incubations, highly significant negative linear relationships were found between the numbers of MCs per well and quantities of both SeFN and CaFN after normalization of the data by logarithmic transformation (SeFN: r values greater than -0.9705; CaFN: r greater than -0.9620; P less than 0.001). Thus, increasing cell densities progressively suppressed ECM formation by MCs. The ECM production was found to be independent of growth activity. AVP significantly increased SeFN (P less than 0.05) and decreased CaFN (P less than 0.001) in subconfluent cultures; Ang II and 5-HT had no effect. Metabolic labeling with 35S-methionine (18 hr, 200 microCi/ml medium) and 2-D electrophoresis of MC lysates resulted in resolution of greater than 500 different radiolabeled intracellular proteins in molecular weight from 110 to 20 Kd over an isoelectric interval of 5.0 to 7.0.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593848 TI - Elevation of albumin synthesis rates in nephrotic patients measured with [1 13C]leucine. AB - Eight patients with a nephrotic syndrome and a histologically-proven kidney disease were compared to age- and sex-matched healthy volunteers. Albumin synthesis rates were measured after injection of 13C-labelled leucine (57 mg/kg body wt, 19.4 atoms%). Plasma volume was determined with 125I-albumin. The fractional synthesis rate of albumin was 7.9 +/- 0.4%/day in control subjects in comparison with a marked elevation to 18.4 +/- 2.0%/day (P less than 0.001) in nephrotic patients. The absolute synthesis rate was 145 +/- 9 mg/kg/day in control subjects compared with 213 +/- 17 mg/kg/day (P = 0.005) in the nephrotic patients. There was a statistically significant correlation between ASR and urinary albumin loss (P = 0.035) and serum cholesterol concentration (P = 0.007). The calculated oncotic pressure was significantly lower in the nephrotic group than in the controls (P less than 0.001), but was without correlation with ASR. PMID- 1593849 TI - Stone-forming potential of milk or calcium-fortified orange juice in idiopathic hypercalciuric adults. AB - Milk and orange juice (OJ) fortified with calcium-citrate-malate (CCM; calcium citrate-malate salt is a coined term to describe a trademarked calcium delivery system found only in Citrus Hill Plus Calcium) were evaluated for their potential to alter urine chemistries and crystallization during the course of an eleven week, crossover study. Six male and six female, non-stone-forming, idiopathic hypercalciuric adults consumed 600 mg per day as beverage calcium for four consecutive weeks. The results show that both milk and CCM-fortified OJ (CCM-OJ) were well tolerated by male and female hypercalciurics since few significant changes occurred in overall urinary chemistry profiles. CCM-OJ did, however, significantly (P less than or equal to 0.05) increase urinary pH relative to milk in both sexes and urinary citrate concentration in women only. Both of these urinary parameters were significantly increased by CCM-OJ in both sexes relative to the basal period. The combined pH and citrate effects are recognized to protect against calcium oxalate stone formation through formation of the soluble calcium citrate salt. These data indicate that either milk or CCM-fortified orange juice can be consumed, at least within the limits tested, as a dietary source of calcium without increasing the risk of stone formation in a calcium sensitive subpopulation. That the urine chemistries and crystallization of such calcium-sensitive individuals does not significantly change with the consumption of either beverage implies that the urine of normal individuals would be exceedingly unlikely to change as well. PMID- 1593850 TI - Biosynthetic and proliferative characteristics of tubulointerstitial fibroblasts probed with paracrine cytokines. AB - Fibroblasts in parenchymal organs potentially contribute extracellular matrix to local fibrogenic processes. This contribution, in some circumstances, may be initiated by cytokines disseminated from inflammatory lesions. Different populations of fibroblasts, however, might respond distinctively to this cytokine bath depending on the microenvironment in which they reside. We have begun to explore this issue using syngeneic, low-passage fibroblasts cultured in serum free media that were derived originally from the dermis (DFBs) and from tubulointerstitium (TFBs) of the kidney. Our findings indicate that, while fibroblasts from each compartment appear similar at the ultrastructural level, there are a variety of functional differences which distinguish their proliferative response, and their collagen secretory response (types I, III, IV, and V) following challenge with various doses of immune-relevant cytokines (TGF beta, EGF, IL-1, IL-2 and gamma IFN) in culture. DFBs, for example, express more surface EGF receptors than do TFBs, and, as a consequence, exhibit a more robust proliferative response to EGF in serum-free media. Unstimulated DFBs also secrete more collagen types I and III than TFBs, while unstimulated TFBs secrete more types IV and V. The expression of these collagens in TFBs was confirmed by Northern blot hybridization. When these sets of fibroblasts were further stimulated by cytokines, some of the cytokines not only differentially effect the secretion of various species of collagens within the same group of cells, but also between cells from populations which are anatomically distinct. DFBs, furthermore, at mid-level doses of cytokine, demonstrated a general trend towards less secretion of all types of collagen (particularly for TGF beta, EGF, and IL 2), while TFBs seemed less repressive. In TFBs the cytokine-induced responses for collagen types I and III tended to be discordant, and for types I and IV EGF inhibited, while TGF beta stimulated the secretory process. These findings speak collectively for the presence of a functional heterogeneity among organ-based populations of syngeneic fibroblasts in normal tissues. PMID- 1593851 TI - Calcium oxalate crystallization in urine: role of urate and glycosaminoglycans. AB - Increasing the concentration of urate promotes the crystallization of calcium oxalate in human urine. In this study the possibility that this effect might be attributable to the attenuation of the inhibitory activity of urinary glycosaminoglycans (GAGs) was explored. Urine sample were collected from 20 men with no history of urolithiasis and the intact GAGs removed by 10 kDa ultrafiltration. Ten of these specimens, designated type A, spontaneously precipitated calcium oxalate crystals when the median urate concentration was increased from 3.13 to 7.33 mmol/liter by the addition of a saturated solution of sodium urate. In the remaining more dilute urines, which were designated type B, spontaneous calcium oxalate crystallization did not occur when the median urate concentration was raised from 2.20 to 6.40 mmol/liter. In these samples crystallization was induced by a standard load of oxalate above the empirically determined metastable limit. Addition of urate significantly reduced the median metastable limit from the control value of 125 to 46 mumol oxalate, and the volume of calcium oxalate deposited was increased fourfold from 25,000 to 104,000 microns 3/microliters. The median size of the precipitated particles was also increased in the presence of urate from 12.06 microns to 14.3 microns; this was confirmed by scanning electron microscopy, which demonstrated that the crystals precipitated in the presence of added urate, though individually smaller, were markedly more numerous and more highly aggregated than those deposited in the control. Re-ultrafiltration of the urines to which urate had been added did not alter the urate concentration, and SEM examination of the ultrafiltration membranes did not reveal the presence of any particulate material.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593852 TI - Histopathological findings in well-functioning, long-term renal allografts. AB - One hundred and twenty-eight patients with a first cadaveric kidney allograft participated in a prospective, randomized, clinical trial comparing triple treatment, consisting of initial low-dose cyclosporine (CsA), azathioprine (Aza) and methylprednisolone (MP), with all possible combinations of two immunosuppressive drugs. A protocol core biopsy was performed on all patients with a functioning graft two years after transplantation. The histological findings were evaluated blindly and correlated to possible risk factors for renal allograft damage. The most common histological features were diffuse fibrosis in 62% of biopsies, tubular atrophy in 64% and diffuse inflammation in 30%. Two other important findings were glomerulosclerosis (43%) and vascular intimal proliferation (36%). The histological findings were scored mostly mild. A total of 77% (69 of 89) of patients had normal or only slightly increased serum creatinine. Decreased graft function was related to increased interstitial fibrosis, inflammation, glomerulosclerosis, mesangial matrix increase of glomeruli, intimal proliferation of vessels and tubular atrophy. These findings are characteristic, but not pathognomonic, of chronic renal allograft rejection both in experimental models and in humans. Possible risk factors were correlated to graft histology. Donor age correlated strongly with mesangial matrix increase, intimal proliferation, and tubular atrophy; there was no correlation with interstitial changes. The number of acute rejections and cold ischaemia time did not correlate with any one of the histological findings at two years following transplantation. Cyclosporine dose and concentration had a negative correlation to interstitial inflammation. A "chronic allograft damage index" was eventually created for the comparison of the four different treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593853 TI - Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease. AB - Patients with nephrotic syndrome and varying degrees of renal failure, including those on chronic hemo- and peritoneal dialysis, may have low serum concentrations of total 1,25-dihydroxyvitamin D [1,25(OH)2D]. However, it is unknown whether the true activity of 1,25(OH)2D is better reflected by the free 1,25(OH)2D fraction. We measured total 1,25(OH)2D, free 1,25(OH)2D, and vitamin-D-binding protein (DBP) in normal subjects (group A), subjects with moderate renal failure (group B), subjects on hemodialysis (group C), subjects on peritoneal dialysis (group D), and subjects with nephrotic syndrome (group E). The serum concentrations of total and free 1,25(OH)2D decreased with worsening renal function in groups A through C, with a high degree of correlation (r = 0.974, P less than 0.0001). Levels of DBP and the percent free 1,25(OH)2D remained constant in these groups. Patients on peritoneal dialysis and nephrotic patients had lower levels of DBP (203 +/- 14 micrograms/ml and 371 +/- 46 micrograms/ml, respectively) than normal subjects (436 +/- 33 micrograms/ml) and had significantly higher percent free 1,25(OH)2D (0.98 +/- 0.13% and 1.27 +/- 0.14%, respectively) compared to 0.63 +/- 0.03% (P less than 0.05). Thus, the loss of DBP in these patients correlated with a rise in the percent free 1,25(OH)2D. We conclude that levels of total 1,25(OH)2D are an accurate representation of 1,25(OH)2D status in normal subjects, subjects with renal insufficiency without nephrotic syndrome, and hemodialysis patients. In peritoneal dialysis and nephrotic patients, who lose DBP, measurements of free 1,25(OH)2D may be necessary in order to accurately assess 1,25(OH)2D status. PMID- 1593854 TI - Effects of dietary protein in patients with chronic renal transplant rejection. AB - Dietary protein restriction reduces proteinuria and slows the progression of renal failure in a variety of renal diseases in native kidneys. Such beneficial effects may be mediated by the multiple renal effects of dietary protein including those on glomerular capillary hemodynamics and the renin-angiotensin system. The role of dietary protein restriction in the management of chronic renal transplant rejection is, however, unclear. This study was therefore undertaken to examine the effects of dietary protein restriction in patients with chronic rejection. Fourteen patients with biopsy proven chronic rejection, who had been on a self-selected home diet of 1.0 +/- 0.1 g protein/kg/day, were randomly assigned, using a crossover design to two 11-day periods, one on a low protein diet (0.55 g/kg/day) and the other on a high protein diet (2 g/kg/day). The effect of these diets on renal hemodynamics, proteinuria, plasma renin activity, and nutritional status was examined. The low protein diet was associated with a significant improvement in glomerular permselectivity in all patients as evidenced by a significant fall in the fractional clearance of albumin and IgG and reduction in 24-hour urinary excretion of total protein, albumin and IgG without any change in blood pressure, glomerular filtration rate, or renal plasma flow. Compared to the proteinuria at the beginning of each diet, a high protein diet did not increase but a low protein diet significantly decreased the proteinuria. The low protein diet was also associated with a significant reduction in plasma renin activity, suggesting that part of the beneficial effect of protein restriction was related to the suppression of the renin-angiotensin system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593855 TI - In vitro and in vivo interleukin-8 production in human renal cortical epithelia. AB - The signals resulting in leukocytes infiltrating the tubulointerstitial compartment during renal inflammatory disease are not well understood. A recently described cytokine, interleukin-8 (IL-8), has been demonstrated to be chemotactic for lymphocytes and neutrophils at picomolar and nanomolar concentrations, respectively. Cytokeratin positive, renal cortical epithelial cells (RCEC) with tubular attributes were cultured from kidney tissue from six human subjects. We report that these human renal cortical epithelial cells in primary cell culture respond to either IL-1 beta, TNF or LPS in both a time- and dose-dependent manner by expressing IL-8 mRNA and secreting antigenic IL-8 peptide. In addition, RCEC were found to be strongly positive for cell-associated antigenic IL-8 peptide by immunostaining after 24 hour incubation with IL-1 beta, TNF and LPS. To ascertain whether IL-8 was present in renal disease associated with infiltrating leukocytes, we performed immunohistochemistry on renal biopsy specimens from patients with acute allograft rejection. Both proximal and distal tubular epithelial cells were found to be strongly positive for cell-associated antigenic IL-8. These findings suggest that the human renal tubule epithelial cell may actively participate in acute inflammatory processes in the kidney, including allograft rejection, by effecting and directing leukocyte chemotaxis via the production of IL-8. PMID- 1593857 TI - The parietal podocyte: a study of the vascular pole of the human glomerulus. PMID- 1593856 TI - Effects of thromboxane synthase inhibition with CGS 13080 in human cyclosporine nephrotoxicity. AB - Cyclosporine is a potent immunosuppressive agent, however, its use is limited by nephrotoxicity. Increased production of the potent vasoconstrictor thromboxane A2 contributes to cyclosporine nephrotoxicity in animal models, but the role of thromboxane in human cyclosporine nephrotoxicity has not been established. We therefore studied cyclosporine-treated renal allograft recipients who had evidence of toxicity manifested by decreased renal function. We measured GFR and PAH clearance (CPAH) before, during, and one week after a 48-hour intravenous infusion of the thromboxane synthase inhibitor CGS 13080. At baseline, the urinary excretion of TXB2 and 2,3-dinor-TXB2 was elevated in the study patients compared to healthy subjects. CGS 13080 infusion caused selective and nearly complete inhibition of thromboxane metabolite excretion in all patients. Mean CPAH improved 33% from 223 +/- 45 to 298 +/- 59 ml/min/m2 (P = 0.055) during infusion, while mean GFR improved 9% from 50.1 +/- 3.9 at baseline to 54.6 +/- 4.5 ml/min/1.73 m2 (P = 0.111). The effect on GFR occurred primarily in those patients taking calcium channel blockers. The mean increase in GFR in these 5 patients was 10.0 +/- 2.8 versus -1.0 +/- 2.8 ml/min/m2 in the remainder. We conclude that thromboxane synthase inhibitors may be useful in attenuating the nephrotoxic effects of cyclosporine following renal transplantation. PMID- 1593858 TI - A new method culturing renal cells under permanent superfusion and producing a luminal-basal medium gradient. PMID- 1593859 TI - Regeneration after acute tubular necrosis. PMID- 1593860 TI - Transgenic rats carrying the mouse renin gene--morphological characterization of a low-renin hypertension model. AB - Transgenic rats [TGR; strain name TGR(mRen2)27] harboring the mouse Ren-2 renin gene have been recently generated as a model for the study of primary hypertension that offers the advantage of a clearly-defined genetic alteration. Expression of the mouse Ren-2 gene causes severe hypertension (200 to 260 mm Hg) which is responsive to converting enzyme inhibitors. Compared to control transgene-negative littermates, plasma renin and angiotensin II values are lowered in TGR, whereas plasma prorenin values are strongly elevated. The adrenal gland in TGR shows marked overexpression of mouse renin messenger RNA; in situ hybridization using a 35S-labelled mouse-renin RNA probe reveals that enhanced renin expression is mainly localized to cells of the zona glomerulosa and outer zona fasciculata. Immunohistochemically, renin protein in the TGR adrenal gland is stored in larger quantities than in controls. Adrenal transgene expression probably accounts for most of the elevated plasma prorenin level in TGR, since bilateral adrenalectomy (ADX) causes a significant decrease in prorenin level (318 +/- 79 ng angiotensin I/ml/hr before ADX to 70 +/- 43 ng 4 days after ADX, P less than 0.0005). In the kidney, renin synthesis is almost completely suppressed in TGR. In situ hybridization demonstrates that few juxtaglomerular afferent arterioles express renin. Immunohistochemically, the TGR kidney shows significantly reduced renin and angiotensin II immunoreactivity at the afferent arteriole. Ultrastructural analysis of the afferent arteriolar wall frequently shows the complete absence of renin secretory granules since the granular cells are mostly converted into smooth muscle cells. Beginning at an age of approximately four to six months, TGR develop hypertension-related alterations and pathological lesions in various tissues. In the kidney, the wall thickness of arterioles and arteries is strongly increased, and glomerular lesions including different stages of sclerosis are observed. The thoracic aorta displays a considerable increase in tunica media thickness due to both myocyte hypertrophy and interstitial fibrosis. Coronary arteries and arterioles of the heart are thickened and perivascular fibrosis is observed. The data show that TGR(mRen2)27 transgenic rats display all typical characteristics of hypertensive pathology, making them an interesting model for therapeutic interventions. The fact that these changes occur in animals with a single gene difference to normotensive rats makes them a particularly suitable model for studies on gene-related hypertensive processes. PMID- 1593861 TI - Induction and progression of experimental lupus nephritis: exploration of a pathogenetic pathway. PMID- 1593862 TI - A high-affinity folate binding protein in proximal tubule cells of human kidney. AB - High-affinity 3H-folate binding in solubilized brush border membranes of human kidney cortex display characteristics such as apparent positive cooperativity typical of specific folate binding. The folate binding activity and the activity of the brush border membrane-marker enzyme, gamma-glutamyltransferase, were eightfold higher in brush border membranes compared to crude kidney homogenate. Ultrogel AcA 44 chromatography revealed a major (Mr approximately 100 kDa) and a minor (Mr approximately 25 kDa) folate binding protein in brush border membranes. The large molecular size form may represent a membrane-derived hydrophobic folate binding protein inserted in Triton X-100 micelles. This notion was supported by the identical molecular weights of the 100 kDa and 25 kDa folate binding peaks determined by sodium dodecylsulfate polyacrylamide gel electrophoresis and immunoblotting. The folate binding protein in renal brush border membranes cross reacted with rabbit antibodies against 25 kDa human milk folate binding protein, and showed immunoprecipitation in the presence of these antibodies. Paraffin embedded sections of kidney cortex showed immunostaining of cells in the convoluted proximal tubules after exposure to rabbit antiserum (1:8000 dilution). Glomeruli and distal tubules showed no immunostaining. PMID- 1593863 TI - Induction of "wire-loop" lesions by murine monoclonal IgG3 cryoglobulins. AB - We have recently demonstrated that an IgG3 rheumatoid factor (RF) monoclonal antibody (mAb), clone 6-19, derived from unmanipulated autoimmune MRL/MpJ-lpr/lpr mice, is able to generate cryoglobulins via a non-immunological IgG3 Fc interaction, and to induce an acute glomerulonephritis associated with cryoglobulinemia. Using this experimental model, we have characterized the glomerular lesions induced by the 6-19 RF monoclonal cryoglobulin, in particular the ultrastructural localization of the cryoglobulin deposits. Although their initial localization was confined to the mesangium, the 6-19 cryoglobulins were progressively accumulated in the subendothelial spaces of glomerular capillary walls, leading to the formation of glomerular lesions resembling the "wire-loop" lesion characteristically described for lupus nephritis. In addition, we have found that identical glomerular "wire-loop" lesions were induced by the 6-19-J558 hybrid antibody, composed of the 6-19 gamma 3 heavy chain and J558 lambda 1 light chain, which loses the RF activity, but retains the cryoglobulin activity. These results strongly suggest that the direct deposition of IgG3 cryoglobulins by itself, without involvement of immune complex formation, results in the generation of the classical "wire-loop" lesion characteristic of lupus nephritis. In addition, we have found that similar "wire-loop" lesions were generated by one anti-DNA mAb derived from (NZB x NZW)F1 hybrid mice, and two of four IgG3 mAb of unknown specificities, derived from MRL/MpJ-lpr/lpr mice. The absence of significant glomerular lesions, in spite of large amounts of cryoglobulins, in mice receiving two IgG3 mAb suggests the importance of physicochemical property of cryoglobulins to provoke glomerular lesions. PMID- 1593865 TI - The Association for Academic Surgery: what a concept! AB - I hope that I have neither bored you nor spoken of things that anyone could question or take as offensive. My simple intent was to relate what I truly believe. The discipline of surgery is indeed a noble profession. The portion of this profession that we identify as academic surgery represents a most prestigious and advantageous vocation. It places us in a position to aid our fellow man in a time of true need and vulnerability, to satisfy our intellectual curiosity, and to be good stewards of our time and talents. But, most of all, it gives us each and every day a sense of purpose, accomplishment, and fulfillment. I believe the Association for Academic Surgery represents a concept that helps each of us attain these goals. It has for me. During this past year, it has been both an honor and an enjoyment to be your President. For that I am most grateful. Thank you. PMID- 1593864 TI - Cisplatin-induced alterations in renal structure, ammoniagenesis and gluconeogenesis of rats. AB - Cisplatin [cis-diamminedichloroplatinum (II): CDDP] is a widely used cancer chemotherapeutic agent which has been shown to cause dose-related acute renal failure. The kidney damage is histologically characterized by widespread tubular necrosis, predominantly found in the third segments (S3) of the proximal tubules. To identify the intranephron targets of CDDP more precisely, we examined alterations in ammoniagenesis (AMG) and gluconeogenesis (GLG) using rat kidney slices (for AMG and GLG), tubule suspensions (for GLG), and microdissected nephron segments (for AMG). Ultramicroassay of AMG was carried out using the enzymatic cycling method, and GLG was measured by the HK/G6PHD method. GLG obtained from kidney slices and tubule suspensions on day 3 and day 7 following CDDP treatment did not change significantly from levels in control rats. In contrast, AMG increased on day 3 in the first and third kidney slices cut from the surface inward and decreased significantly on day 7 in the third and fourth slices. Microdissected nephron segments examined on day 7 showed decreased AMG in the second segments (S2; 20.3 +/- 7.7 pmol/mm/15 min vs. 78.7 +/- 9.7 for control, P less than 0.005) and the third segments (S3; 26.3 +/- 14.4 pmol/mm/15 min vs. 79.2 +/- 7.8 for control, P less than 0.005) of the proximal tubules. Additionally, we observed morphological changes under light microscopy to examine the relationship between metabolism and morphology. On day 3 following the CDDP treatment, typical acute tubular necrosis was seen primarily localized in the outer stripe of the outer medulla, while on day 7 the lesion appeared to be recovering. Our data imply a prominent dissociation between renal metabolic and morphologic changes induced by CDDP. PMID- 1593866 TI - Revisiting our roots. PMID- 1593867 TI - Leukocyte-depleted reperfusion of transplanted human hearts prevents ultrastructural evidence of reperfusion injury. AB - The present study examines whether leukocyte depletion can prevent postreperfusion ultrastructural injury in transplanted human hearts. Thirty-two patients undergoing orthotopic cardiac transplantation were randomized to receive either enriched, warm, whole blood (Group I; n = 16) or enriched, warm, leukocyte depleted blood (Group II; n = 16) reperfusion. Donor hearts were arrested with 1 liter of 4 degrees C crystalloid cardioplegia and topically cooled. RV endomyocardial biopsies taken at end-ischemia and following reperfusion were assessed in a blinded fashion and graded according to injury (1 = minimal to 4 = severe). The mean ischemic time (Group I = 142 min, Group II = 153 min) was similar in the two groups. End-ischemic biopsies showed mild-moderate interstitial edema and mild capillary endothelial swelling in both groups with similar injury scores (Group 1 = 1.3 +/- 0.09 (means +/- SEM), Group 2 = 1.25 +/- 0.08). Postreperfusion biopsies in Group I showed nuclear chromatin clumping, moderate mitochondrial swelling, marked capillary endothelial swelling, and marked interstitial edema with a grade of 2.6 +/- 0.14 (P less than 0.001, paired t test). In contrast, postreperfusion biopsies in Group II showed minimal changes with a grade of 1.33 +/- 0.09, P less than 0.0001 in comparison to Group I Leukocyte-depleted reperfusion of human transplanted hearts prevents ultrastructural injury. This may allow safe extension of the ischemic period and result in improved graft function. PMID- 1593868 TI - Standardization of skeletal muscle ischemic injury. AB - Observations on skeletal muscle function after a timed ischemic interval suggests significant interanimal variability. The purpose of this study is to compare the use of function versus time as a method for standardizing the degree of ischemic injury. Muscle function was measured by recording the isometric contraction to direct supramaximal tetanic stimulation of the anterior tibialis muscle (AT). Muscle cell viability was determined by the reduction of triphenyltetrazolium chloride (TTC)/g tissue measured by a spectrophotometric assay. Twenty-four New Zealand White rabbits underwent an interval of ischemia to one anterior tibialis muscle produced by collateral ligation and unilateral inflow control, using the contralateral AT as a control. The duration of ischemia was determined by one of three methods: Group I, n = 8, underwent ischemia for 3 hr (3 hr); Group II, n = 8, underwent ischemia until AT muscle function decreased to 20% of control (20%); and Group III, n = 8, underwent ischemia until AT muscle function decreased to less than 5% of control (less than 5%). Following the ischemic injury, both physiologic function and cellular viability were measured and expressed as a percentage of control. After 3 hr of ischemia, the mean function was 15.5 with a standard deviation of 20.2, and the TTC reduced/g tissue was 24.7 with a standard deviation of 24.8. When the ischemic interval was determined by a decline of muscle function to 20% of control, the mean TTC reduced was 33.4 +/- 7.6. The mean TTC reduced, when the ischemic interval was terminated when muscle function reached less than 5% of control, was 13.5 +/- 7.2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593869 TI - Protective anti-lipopolysaccharide monoclonal antibodies inhibit tumor necrosis factor production. AB - Elevated systemic levels of tumor necrosis factor (TNF) have been directly correlated with increased mortality during experimental gram-negative bacterial sepsis. Although monoclonal antibodies (mAbs) directed against gram-negative bacterial lipopolysaccharide (endotoxin, LPS) decrease TNF production in vitro and enhance survival in vivo, the precise relationship between inhibition of TNF secretion and protective capacity has not been defined. We hypothesized that protective anti-LPS mAbs inhibited LPS-stimulated TNF production. To test this hypothesis, we first produced and characterized three anti-LPS mAbs. We then examined the ability of these mAbs to decrease TNF secretion in an in vitro assay using cells from the murine macrophage cell line RAW 264.7. Subsequently, we assessed the protective capacities of these anti-LPS mAbs in a murine mucin peritonitis model of sepsis using live Escherichia coli 0111:B4 bacterial challenge. Our results demonstrated that those anti-LPS mAbs that decreased LPS stimulated TNF secretion in vitro were protective in vivo. We concluded that inhibition of TNF secretion in vitro reflected protective capacity and that anti LPS mAbs may confer protection via abrogation of macrophage TNF secretion. Inhibition of TNF production in vitro may provide a valuable test that may facilitate the selection of protective anti-LPS mAbs. PMID- 1593870 TI - Dendritic outgrowth of myenteric plexus neurons in primary culture. AB - Myenteric plexus neurons derived from neonatal guinea pigs, when exposed to serum, demonstrated a characteristic pattern of growth, including a proliferating outgrowth zone of glial cells, peripheral extension of dendritic processes, and progressive dendritic growth. Serum effects upon dendritic growth, measured morphometrically, was strongly dose- and temporally dependent. Dendritic density was increased 10-fold (120 hr) by the addition of 6% serum, while mean dendritic length was increased 3-fold. Development of cholinergic function was reflected by release of [3H]ACh in response to cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide (10(-10) and 10(-8) M). PMID- 1593871 TI - Insulinotropic potency of lauric acid: a metabolic rationale for medium chain fatty acids (MCF) in TPN formulation. AB - The need for a better lipid system to satisfy the fuel requirements of patients while avoiding the adverse effects of current systems has led to suggestions that medium chain fatty acids (MCFs) be incorporated into TPN-lipid emulsions. Since clinical situations requiring TPN are associated with metabolic processes mediated by insulin, in the present study we have therefore examined the effects of a variety of medium chain fatty acids on insulin release. Using an isolated perifused mouse islet model, various doses of medium chain fatty acids and the essential fatty acid, linoleic acid, were tested and compared. The possibility of an additive effect of an insulinotropic MCF and linoleate when both are provided together was also examined. Effluent perifusate samples collected on ice during these experiments were assayed for insulin by radioimmunoassay. It was found that the ability of 5 mM of a given MCF to stimulate insulin secretion was dependent upon its chain length. Thus, while adipic acid (C6) had no effect, Caprylic acid (C8) had a minimal effect that was not statistically significant, but capric acid (C10) and lauric acid had very potent effects that were of the same magnitude to the effect of linoleate on insulin secretion. When insulin output was assessed as the mean integrated area under the curve during a 20-min perifusion, 5 mM lauric acid enhanced insulin secretion from a basal 7351 +/- 666 pg to 15,756 +/- 1680 pg (P less than 0.01, n = 5). In the same experiments, 5 mM linoleic acid stimulated insulin release to 11,260 +/- 867 pg (P less than 0.05). When C12 and linoleate were added together, each at a submaximally effective concentration of 2.5 mM, insulin output was 12,712 +/- 1011 pg (P less than 0.05, n = 5), which was not statistically different from the values obtained when the islets were perifused with 5 mM of each fatty acid alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593872 TI - Effects of tumor necrosis factor on system ASC-mediated glutamine transport by human fibroblasts. AB - The effects of tumor necrosis factor-alpha (TNF) on glutamine GLN transport by cultured human fibroblasts were studied. Uptake of 3H-GLN was assayed in both the presence and absence of sodium in order to differentiate Na(+)-dependent and Na(+)-independent transport systems. GLN transport was linear (r = 0.99) for at least 15 min and occurred predominantly via a single Na(+)-dependent pathway, consistent with System ASC. Incubation of fibroblasts with TNF (1000 units/ml) for 12 hr resulted in a significant decrease in system ASC-mediated glutamine transport activity. TNF did not alter cell morphology or protein content. Kinetic studies indicated that the decrease in carrier-mediated Na(+)-dependent GLN transport was not due to a change in transporter affinity (Km = 117 +/- 23 microM in controls vs 86 +/- 23 microM in TNF, P = NS), but instead to a 45% decrease in maximal transport rate (Vmax = 4088 +/- 354 pmole/mg protein/30 sec in controls vs 2230 +/- 510 in TNF, P less than 0.05). TNF also decreased Na(+)-independent transport by 50% (mean uptake of 50 microM GLN = 94 +/- 13 pmole/mg protein/30 sec in controls vs 46 +/- 6 in TNF, P less than 0.02). In human fibroblasts, the activity of System ASC, which has generally been viewed as a hormonally unresponsive carrier, is decreased by TNF. This impairment in glutamine transport may result in inadequate amounts of intracellular glutamine to support fibroblast metabolism and possibly function. PMID- 1593873 TI - Cancer cachexia is transmissible in plasma. AB - The cause of cancer cachexia is unclear. Tumors may be competing with the host for ingested nutrients or may be releasing some factor that actively inhibits energy utilization. To explore these questions, plasma was sterilely collected and pooled from 103 terminally cachectic Fischer 344 rats implanted with an experimental sarcoma. Control plasma was collected in similar fashion from 138 nontumor-bearing rats (NTBP). Plasma from tumor-bearing rats (TBP) or NTBP was continuously infused in a randomized, blinded fashion for 4 days into 20 normal rats. During infusion, food intake and nitrogen excretion were measured daily. At sacrifice, body weight and organ masses were determined. Rats receiving TBP demonstrated an immediate and profound anorexia compared with those receiving NTBP. Total food intake during treatment was 31.2 +/- 3.3 (g +/- SEM) in the TBP group versus 48.2 +/- 2.8 in the NTBP group (P less than 0.001 by t test). Likewise, the total decline in body weight was greater in the TBP group as compared with the NTBP group (-35.2 +/- 3.4 versus -14.6 +/- 4.0, P less than 0.001). Mean daily nitrogen balance during treatment was negative in the rats receiving TBP (-14.5 +/- 20.1 mg +/- SEM) while remaining highly positive in the rats receiving NTBP (110.7 +/- 19.3, P less than 0.002). Finally, cardiac and gastrocnemius muscle masses were decreased, while hepatic mass was unaffected. These data demonstrate that the syndrome of cancer-associated cachexia is transmissible in plasma and therefore may be mediated by a circulating molecule or molecules. Identification and purification of the molecule(s) responsible for this effect would have obvious clinical benefits. PMID- 1593874 TI - Mechanism of the beneficial effects of ATP-MgCl2 following trauma-hemorrhage and resuscitation: downregulation of inflammatory cytokine (TNF, IL-6) release. AB - Although ATP-MgCl2 improves hepatocellular function in a nonheparinized model of trauma-hemorrhage and crystalloid resuscitation, it remains unknown whether the beneficial effects of this agent are due to downregulation of the release of the inflammatory cytokines, tumor necrosis factor (TNF), and interleukin-6 (IL-6) under those conditions. To study this, rats underwent a 5-cm laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of maximum bleedout volume was returned in the form of Ringer's lactate (RL). The animals were then resuscitated with four times the volume of shed blood with RL over 60 min. ATP-MgCl2 (50 mumoles/kg body weight each) or an equivalent volume of normal saline was infused intravenously for 95 min. This infusion was started during the last 15 min of RL resuscitation. Plasma levels of TNF and IL-6 were measured at 1.5 hr after the completion of resuscitation by cytokine-dependent cellular assays. Hepatic blood flow was determined by in vivo indocyanine green clearance (corrected by hepatic extraction ratio for indocyanine green), radioactive microspheres, and [3H]-galactose clearance techniques. The results indicate that the levels of circulating TNF and IL-6 increased significantly in the hemorrhaged-resuscitated animals. ATP-MgCl2 treatment, however, markedly decreased the synthesis and/or release of these cytokines to levels similar to the sham group. The markedly decreased hepatic blood flow (as determined by three different methods) and hepatic extraction ratio for indocyanine green were also restored by ATP-MgCl2 treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593875 TI - The early response of the jejunal brush border glutamine transporter to endotoxemia. AB - The early effects of endotoxin (4 hr after a single dose of Escherichia coli LPS, 7.5 mg/kg) on L-glutamine (GLN) transport across the jejunal brush border of rats were studied. Jejunal brush border membrane vesicles (BBMVs) were prepared by a Mg2+ aggregation/differential centrifugation technique. Vesicle purity and integrity were confirmed by a 15-fold enrichment of brush border marker enzymes, osmotic activity, transport overshoots in the presence of sodium, and similar 1- and 2-hr equilibrium values. L-[3H]GLN transport in jejunal BBMVs was measured by a millipore filtration technique. Na(+)-dependent glutamine transport, which accounted for greater than 80% of total transport, was increased twofold in BBMVs from endotoxin-treated rats (67 +/- 5 pmole/mg protein/15 sec vs 38 +/- 3, P less than 0.01). Endotoxin treatment did not alter the activity of the Na(+) independent carrier. Simultaneously, intestinal extraction of glutamine from the bloodstream fell by 56% (15.1 +/- 2.3% in controls vs 6.6 +/- 1.3% in endotoxin treated rats, P less than 0.01). This reduction in the uptake of circulating glutamine could not be accounted for by a fall in the arterial concentration. Thus, soon after endotoxemia brush border glutamine uptake is increased while consumption of glutamine across the basolateral membrane is decreased. This increased uptake may support protein synthesis and may provide a biochemical rationale for the use of early enteral nutrition after the onset of critical illness. PMID- 1593876 TI - A comparison of total body water measurements using whole-body magnetic resonance imaging versus tritium dilution in primates. AB - Standard techniques conventionally used to assess body composition have various drawbacks which include a requirement for specialized equipment and expertise not widely available, radiation exposure, extensive study time periods, and limited clinical utility. Anthropometric methods, which are more clinically feasible, also involve substantially greater calculation error. This study was designed to compare a newly developed whole-body magnetic resonance (MR) imaging technique with standard tritium dilution (THO) to measure total body water (TBW) in eight primates (Macaca fascicularis). Sedated primates underwent whole-body MR imaging (10-12 contiguous 50-mm slices) and TBW was computed using a previously validated program. After 5 days to allow for primate recovery and stabilization, TBW measurements were repeated using THO methodology. Linear regression analysis of TBWMRI (72.1 +/- 5.7% body wt) compared with TBWTHO (73.8 +/- 3.2% body wt) yielded a Pearson correlation of r = 0.8145, P = 0.02 with a mean squared error of 2.14. Whole-body MR imaging determination of TBW correlates well with THO, requires less time (20 min versus 24 hr), and does not expose the subject to radiation. This study suggests that whole-body MR imaging is an accurate technique for in vivo body composition analysis. As demonstrated by the body size of this investigational primate model, the technique maybe particularly applicable to the study of human infants. PMID- 1593877 TI - Coronary vasomotor dysfunction following hemorrhagic shock. AB - Myocardial dysfunction and subendocardial ischemia have been described during hemorrhagic shock, but technical limitations have precluded the in vitro examination of coronary reactivity following hemorrhage. We tested the hypothesis that in vitro coronary artery contraction and relaxation are impaired by hemorrhagic shock (HS). HS was produced in awake rats (n = 6) 24 hr after surgery for arterial cannulation, by bleeding to a mean arterial pressure of 50 mm Hg for 2 hr followed by reinfusion of shed blood. Using a small vessel myograph, reactivity of coronary arterial ring segments from three groups of rats not undergoing HS were compared to coronaries harvested from rats after HS (Group 4). The three nonshock treatments included normal rats without pretreatment (Group 1), rats undergoing prior surgical cannulation alone (Group 2), and rats undergoing prior surgical cannulation followed by nonhypotensive hemorrhage (Group 3). Responses to 125 mM potassium (KCl) and to 10(-6) M serotonin (STN) determined smooth muscle contraction. Acetylcholine administration determined endothelium-mediated smooth muscle relaxation, whereas acetylcholine plus nitroprusside combined determined maximum smooth muscle relaxation. Rats following HS demonstrated impaired coronary arterial smooth muscle contraction to KCl when compared to normal rats, but the response to STN did not differ among groups. Maximum smooth muscle relaxation was significantly lower in rats following HS as compared to rats in Groups 1 and 2. Endothelium-dependent relaxation was significantly impaired when compared to each of the three nonshock groups. Thus, in coronary arteries isolated from neurohumoral influences, HS was associated with diminished smooth muscle contraction and relaxation as well as impaired endothelium-mediated relaxation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593878 TI - Inhibition of the mutant p53 gene in transformation assays. AB - Mutation of the p53 gene is a key element in the development of several human cancers. Intron 4, a noncoding region of the p53 gene, is required for optimal expression of that gene. We have previously shown that nuclear protein binds intron 4 and have defined the protein-binding site. In this paper we address the question, "Does the mutant p53 gene's ability to transform cells to the malignant phenotype depend on protein binding to intron 4?" Using an in vitro assay in which the mutant p53 gene and Ha-ras oncogene cooperate in transformation of cells to the malignant phenotype, we determined the ability of mutant mouse p53 gene constructs, with and without two base pair substitutions at the intron 4 protein-binding site, to participate in malignant transformation. On Day 1, 5 x 10(5) rat embryo fibroblasts were transfected by the calcium phosphate procedure with 10 micrograms of both a mutant p53 gene construct and Ha-ras oncogene. Malignant transformation was evidenced by the formation of discrete foci of heaped-up cells. After 14 days of incubation at 37 degrees C in DMEM and 10% fetal calf serum (8% CO2), the cells were stained with cresyl violet and the foci counted. In three separate experiments, the presence of two base pair substitutions at the intron 4 protein-binding site caused a significant decrease in the number of foci formed (P less than 0.05). PMID- 1593880 TI - Transsternal thoracotomy for bilateral pulmonary metastasis. AB - Advances in the surgical treatment of primary malignancies and the recent chemotherapy have led to an expansion of the surgical treatment of metastatic lung tumors. However, multiple pulmonary metastases are often found and may affect both lungs. It is difficult to reach tumors in the posterior parts of the lung when using a common midsternal approach, especially lesions located in the left lower lobe. We performed transsternal simultaneous bilateral thoracotomy on 10 patients with bilateral lung tumors (9 bilateral metastatic pulmonary tumors and 1 bilateral primary lung cancer). This procedure provides a wide operative field and is an effective method of thoracotomy for patients with bilateral lung tumors. In future, this method should be more actively performed for patients in whom it is indicated. PMID- 1593879 TI - Postoperative adjuvant chemotherapy for operable esophageal cancer: a pilot clinical study. AB - Thirty-eight patients with node positive squamous cell carcinoma of the esophagus were entered into a pilot clinical study using postoperative adjuvant chemotherapy (cisplatinum 100 mg/m2 and methotrexate 150 mg/m2 x 4 cycles) with an intent of improving cure rates and overall survival. Patient compliance was excellent and toxicity minimal. At 24 months of follow-up 22 patients (58%) were disease free, while 14 patients (37%) have relapsed and 2 were lost to follow-up. A highly significant correlation was noted between the number of nodes involved, the grade of the tumour, and the response to chemotherapy. Patients with poorly differentiated tumours and those with more than 4 nodes involved were more likely to develop recurrent disease (P less than 0.01 and P less than 0.005). We conclude that postoperative chemotherapy following resection for carcinoma of the esophagus is well tolerated with minimal side effects. It may also have an impact on improving disease free and overall survival. PMID- 1593881 TI - Melanoma of the external ear. AB - Management of melanoma of the external ear is controversial. Thirty-one patients treated for this disease were identified at our institution between January 1, 1974 and December 31, 1989. Follow-up was an average of 7.12 years (range 1-15). Local therapy performed included 16 wedge resections, 3 split thickness skin grafts after excision to the perichondrium, 10 partial and 2 total amputations. There were two local recurrences, four metachronous cervical metastases, and four distant metastases. Three elective and five therapeutic neck dissections were performed. Survivors at 1, 5, and 10 years were 93, 77, and 47%, respectively. There was no relationship between DNA ploidy, local surgical therapy, and eventual recurrence. Clinical stage and tumor thickness demonstrated a statistically significant correlation with likelihood of recurrence (P = .02 and .05). There is no evidence that melanoma of the ear has a poorer prognosis or different prognostic factors than melanoma at other cutaneous sites. In selected cases, local disease can be controlled by excision and skin graft rather than the more aggressive current procedures. PMID- 1593882 TI - Neoadjuvant chemotherapy with cytosine arabinoside by continuous infusion and cisplatin for resectable squamous cell carcinoma of the esophagus. AB - The combination of cisplatin and cytosine arabinoside has been shown in experimental models to be synergistic. We conducted a pilot study of cytosine arabinoside and cisplatin in unresectable or metastatic cancer of the esophagus in five patients and found significant activity, also on visceral metastasis. Therefore, we decided to examine this combination in the neoadjuvant setting. Since January 1989, eight patients with squamous cell carcinoma esophageal cancer were treated with two cycles of cytosine arabinoside (50 mg/m2) by continuous infusion for 4 days and by cisplatin (100 mg/m2) on the 5th day. Their ages ranged from 54-79 years. One patient had Stage I, three had Stage II, and four had Stage III disease. Responses assessed by endoscopy and computed tomographic (CT) scan prior to surgery were three with partial response, three with minor response, and two with no response. Only six patients were surgically resectable after chemotherapy. Toxicity consisted of grade 3 (one patient) and grade 4 (two patients) neutropenia, grade 3 (three patients) anemia, and grade 3 (two patients) and grade 4 (three patients) thrombocytopenia. All patients had subjective improvement of dysphagia 4 weeks after chemotherapy. Median survival of the whole group was 7.5 months. We concluded that there was no evidence of synergy of these drugs given in this manner in esophageal carcinoma since the response rate was no different from that achieved with cisplatin alone. PMID- 1593883 TI - Reasons for non-entry in randomized clinical trials for breast cancer: a single institutional study. AB - Reasons for patient non-entry in randomized clinical trials (RCTs) assessing oncologic treatment modalities are not well documented in the literature. We have prospectively recorded reasons for RCT non-entry in breast cancer patients at St. Michael's Hospital, Toronto. From September 1984 to November 1989, 592 consecutive patients were evaluated through the clinical trials office. One hundred six out of the 592 patients were placed into a RCT (17.9%). Protocol ineligibilities accounted for 273 non-entries (46.1%) and protocol eligible but not entered patients accounted for 213 (36.0%) non-entries. The most common reason for protocol ineligibility was advanced age (94 patients). The most common reason for protocol eligible but not entered patients was patient refusal (148 patients). A total of 272 patients in both non-entered groups were identified as having reasons for non-entry that were potentially correctable. In summary, protocol ineligibilities account for the majority of non-entered patients, but patient refusal accounted for the single largest group of potentially correctable non-entries. More dissemination about the merit of RCTs in the lay press and amongst primary care physicians must take place if we are to expediently and efficiently answer important oncologic questions. PMID- 1593884 TI - Soft tissue sarcomas in whites and blacks living in the United States of America. AB - Five hundred four hospitals volunteered reports on 2,355 patients in a long-term study and 645 institutes reported on 3,457 in a short-term study. Out of 5,623 cases of soft tissue sarcoma (STS) reported in white and blacks living in the United States of America, 574 cases (10.2%) were reported in blacks. No striking differences were found between blacks and whites concerning anatomic sites, histologic types, histologic grades, or clinical stages of STS. A higher percentage of patients with recurrences were reported in whites with liposarcoma (37.7% compared to 28.9% in blacks), and leiomyosarcoma (45% in whites compared to 39.1% in blacks). On the other hand recurrences were more frequent in fibrosarcoma and rhabdomyosarcoma in black patients. No significant differences in survival was found between white and black patients with STS. PMID- 1593885 TI - Papillary carcinoma of the thyroid after postpartum thyroiditis. AB - Postpartum thyroiditis is a benign, often self-limited cause of thyroid dysfunction. This report describes the first case of papillary carcinoma arising in a woman with postpartum thyroid disease. Both clinicians and pathologists must keep a high index of suspicion in postpartum patients with persistent thyroid abnormalities, even when a previous biopsy may have disclosed benign disease. PMID- 1593886 TI - Cross-femoral venous bypass in combination with tumor resection. AB - The cross-femoral venous bypass procedure (also known as the Palma/Dale procedure) was introduced for unilateral iliac or common femoral vein occlusions resulting in chronic deep venous insufficiency. We have utilized the procedure successfully in a patient who required extensive pelvic tumor resection involving sacrifice of pelvic venous collateral channels and unilateral ligation of external, internal, and common iliac veins. The case report and review of the literature are presented. PMID- 1593887 TI - Esophageal cancer: does preoperative chemotherapy make a difference? PMID- 1593888 TI - The influence of hepatic artery ligation and of vasopressin on liver tumour blood flow in rats. AB - The blood flow in an experimental adenocarcinoma in the rat liver was determined with the 133Xe-washout technique before and after hepatic artery ligation (HAL). There was an initial reduction of the washout of 50%. This was further reduced after 1 day by 50%, which was maintained for 7 days. Seven days after HAL or sham procedures the 133Xe-washout was of similar magnitude in the liver tumours, although after the sham procedure the tumours were larger (3.4 g vs. 1.5 g). The estimated tumour blood flow was then approximately 0.04 ml x min-1 x g-1. The influence on normal liver parenchyma of HAL was a reduction at 30 minutes, which was maintained for 7 days. Postacton--a synthetic vasopressin--did not influence the 133Xe-washout in normal liver parenchyma in non-tumour, as well as in tumour bearing animals. There was no influence of Postacton on the 133Xe-washout in the liver tumours. Thirty minutes after HAL Postacton gave a reduction of blood flow in normal liver parenchyma of tumour-bearing animals, which is thus only from the portal vein. In tumours Postacton did not significantly reduce the tumour blood flow immediately after HAL. PMID- 1593889 TI - Sphincter-preserving extended resection for locally advanced rectosigmoid carcinoma involving the urinary bladder. AB - Radical en bloc resection has gained acceptance in the management of locally advanced colorectal carcinoma. Total pelvic exenteration has been advocated as treatment for rectosigmoid cancers involving adjacent genitourinary structures. We report a series of 10 patients who underwent total cystectomy with en bloc segmental colorectal resection and restoration of intestinal continuity. All margins, including the distal colorectal margin of resection, were pathologically uninvolved by tumor. The median follow-up on these patients was 44 months and the mean survival was 42.5 months. The local recurrence rate (20%) and survival rates are comparable to those in reports describing pelvic exenteration for colorectal cancer. Our patients had normal postoperative bowel function. An extended colorectal resection, including a total cystectomy with rectal sphincter preservation, is occasionally possible when tumor-negative resection margins can be achieved. By restoring intestinal continuity, such an operation provides an improved quality of life, and more importantly, fulfills the criteria for an oncologically sound operation. PMID- 1593890 TI - Whole liver intraoperative irradiation after partial hepatectomy produces minimal functional and pathologic lesions. AB - Intraoperative radiation therapy (IORT) was delivered to remnant rat liver after partial hepatectomy to determine the chronic effects of treatment on survival, blood chemistry, liver weight, and histology. Survival at one year was 100%. Remnant liver weight was markedly increased in all animals. Liver function appeared to be unaltered in all groups and at all observation times. Inflammatory cell infiltration occurred immediately after treatment in all animals, showing a slight progression until day 45; by day 180 the values had returned to baseline. Vascular changes were seen early in all groups, then progressively decreased; the vascular score was back to baseline at days 180 and 365. Nuclear alterations were observed in both irradiated and nonirradiated hepatic cells; in all cases these were limited to isolated or focal areas of hepatocytes. There was little fibrosis formation and by day 180 all scores were back to baseline. We conclude that the chronic effects of whole liver IORT after one-third hepatectomy are minimal in the rat and are similar to those observed after surgery alone. PMID- 1593891 TI - Influence of surgical stress on bactericidal activity of neutrophils and complications of infection in patients with esophageal cancer. AB - The association between surgical stress-related depression in bactericidal activities of neutrophils and the occurrence of postoperative infections was investigated. Bactericidal activities of neutrophils were measured in 19 patients undergoing esophagectomy, 15 gastrectomy, and 16 cholecystectomy. Five patients had complications of infection following esophagectomy. In 45 patients with no postoperative infections, intracellular killing index (KI) and superoxide anion production (SOP) levels decreased on postoperative day 1 while myeloperoxidase (MPO) activity increased on days 1-3. In 5 patients with esophageal cancer and postoperative infections, decreases in KI and SOP were less prominent, as compared to findings in 14 esophageal cancer patients without such problems but the MPO activity decreased on days 1-3. This evidence suggests that postoperative septic complications are not directly associated with surgical stress-related transient depression of bactericidal activities immediately after surgery but rather with neutrophil-mediated tissue injuries based on degranulation. PMID- 1593892 TI - Modified presternal esophagogastroplasty in the treatment of esophageal cancer. AB - Six male patients with locally advanced esophageal cancer underwent surgical treatment including modified presternal esophagogastroplasty. The main reason for this kind of esophagogastroplasty was anticipated risk of transplant gangrene or anastomotic leak. Esophagoplasty technique provides a possibility for prolonged enteral nutrition and facilitates the further reconstruction in case of partial transplant gangrene. There was no hospital mortality. All patients, despite postoperative complications, began their oral food intake with good tolerance of the regular diet. PMID- 1593893 TI - A note on neuronal firing and input variability. AB - The Ornstein-Uhlenbeck process with a constant forcing function has often been used as a model for the subthreshold membrane potential of a neuron. The mean, variance and coefficient of variation of the first passage time to a constant threshold are examined for this model in the limit of small synaptic noise and low thresholds. A comparison is made between the asymptotic results of Wan & Tuckwell, who used perturbation analysis, and several computationally simpler approximation methods. A generalization of Stein's method gives an overestimate of the mean interval while an approximation by a Wiener process with linear drift gives an underestimate of the mean interval. These bounds are simple to calculate and can be used as a prelude to a more detailed perturbation analysis. PMID- 1593894 TI - Intercellular conduction velocity variability as the basis for re-entrant arrhythmias in the ischemic myocardium. AB - Re-entrant arrhythmias are the major cause of death from cardiovascular disease. A number of models or mechanisms have been proposed to explain the generation of re-entrant arrhythmias in the ischemic or damaged heart. However, none of these models can qualitatively predict the formation of re-entry movements with no modifications of the basic electrophysiologic characteristics of the myocardium. In this presentation we evaluate the concept that the generation of re-entrant arrhythmias is due to increased variance in the conduction characteristics of the cardiac tissue, rather than to modification of these properties. Using a model of a homogeneous two-dimensional matrix of excitable conducting cells, we derived the relationship between the relative standard deviation (RSD) and the probability of occurrence of a local ordered dispersion of velocities shown to have the potential to result in circular propagation. This probability was found to be insignificant when the RSD was lower than 10%, but increased dramatically for RSDs greater than 10%. On the basis of experimental RSD, the calculated probability for circus movement formation is one in 10,000 normal heart beats and one in two ischemic heart beats. The model provides new insight into the mechanism of re-entrant arrhythmias as well as new tools for diagnosis. PMID- 1593895 TI - A two-locus model of speciation. AB - Speciation is considered as the evolution of partial or complete cross incompatibility between the carriers of genes (at a locus called "object locus") that distinguish the prospective species populations. The mating relations at the object locus are modified by the alleles at a second mating modifier locus. Based on a widely applicable concept of fitness and mating preference, it is shown that heterozygote disadvantage in fitness at the object locus is necessary for speciation, which corroborates Wallace's hypothesis. It is pointed out that the difference between sympatric and parapatric speciation essentially lies in the mechanisms stabilizing the polymorphism required at the object locus as a prerequisite for speciation. In the presence of recombination between the object and mating modifier locus speciation may be prevented by forces maintaining gametic phase imbalance between these loci such as can result from unidirectional gene flow between parapatric populations. PMID- 1593896 TI - Network analysis of intermediary metabolism using linear optimization. I. Development of mathematical formalism. AB - Analysis of metabolic networks using linear optimization theory allows one to quantify and understand the limitations imposed on the cell by its metabolic stoichiometry, and to understand how the flux through each pathway influences the overall behavior of metabolism. A stoichiometric matrix accounting for the major pathways involved in energy and mass transformations in the cell was used in our analysis. The auxiliary parameters of linear optimization, the so-called shadow prices, identify the intermediates and cofactors that cause the growth to be limited on each nutrient. This formalism was used to examine how well the cell balances its needs for carbon, nitrogen, and energy during growth on different substrates. The relative values of glucose and glutamine as nutrients were compared by varying the ratio of rates of glucose to glutamine uptakes, and calculating the maximum growth rate. The optimum value of this ratio is between 2 7, similar to experimentally observed ratios. The theoretical maximum growth rate was calculated for growth on each amino acid, and the amino acids catabolized directly to glutamate were found to be the optimal nutrients. The importance of each reaction in the network can be examined both by selectively limiting the flux through the reaction, and by the value of the reduced cost for that reaction. Some reactions, such as malic enzyme and glutamate dehydrogenase, may be inhibited or deleted with little or no adverse effect on the calculated cell growth rate. PMID- 1593897 TI - Network analysis of intermediary metabolism using linear optimization. II. Interpretation of hybridoma cell metabolism. AB - The reaction network of intermediary metabolism in the mammalian cell has been studied using linear optimization. Experimental measurements of metabolite fluxes entering and leaving hybridoma cell line 167.4G5.3 have been used to interpret the interactions of nutrients and the demand for intermediates for growth. We have ascertained the effects of waste production and energy loads on the cell growth rate using linear optimization. This analysis has shown that neither the maintenance demand for ATP nor the antibody production rate limit growth rate at normal experimental conditions. In addition, the cell uses its nutrients for growth with only 57-78% efficiency, due to the large secretion of alanine. The sensitivity of the growth rate with respect to the demand for cofactors and the supply of nutrients is given by the shadow price for each constraint. The shadow prices have shown that amino acids are the limiting nutrients at experimental conditions. The sensitivities of the growth rate to flux through reactions, given by the reduced costs, have shown that flux through the reaction glutamate dehydrogenase may actually slow down cell growth. We have also found that intermediates with lower shadow prices, and thus with lower value to the cell, are the precursors to compounds secreted from the cell. The shadow prices are also a means for comparing the costs of synthesizing various intermediates in terms of the two major nutrients, glucose and glutamine. At anaerobic conditions, glucose and glutamine have similar values to the cell, and the cost to synthesize most intermediates in terms of glucose is identical to the cost in terms of glutamine. At aerobic conditions, glucose is nearly twice as valuable to the cell as glutamine. PMID- 1593898 TI - A calcium model with random absorption: a stochastic approach. AB - Absorption of calcium, or any mineral, by the body is subject to the random fluctuations typical of diffusion through membranes. In this paper we consider the absorption of calcium from the gut as a white noise process added to the deterministic model of Sen & Mohr (1990, J. theor. Biol. 142, 179-188). The first two moments for the amount of calcium in the extracellular fluid (ECF) have been derived using the Ito Calculus. A confidence interval for the total amount of calcium in the ECF is constructed. The equations for the first two moments of the fraction of dose calcium in the ECF are also given. Suggestions are made for the collection of experimental data in a form which should be helpful in investigating the magnitude of the stochastic effect. PMID- 1593899 TI - Propagation of information in MetaNet graph models. AB - Information flow in metabolic networks has been studied with a graph model which represents the biochemical transformations occurring in the system under investigation. The "signal strength", an algebraic expression which estimates the probability that an intermediate metabolite is bound to a given enzyme, has been used to derive the "signal transmittance", the fraction of the informational signal at one intermediate that reaches another intermediate. The transmittance has been used to derive the "response ratio", the sensitivity of the rate of change of information at one metabolite consequent to a perturbation at another metabolite. Because the graphical representation corresponds to the biochemical events presumed to occur in the network, these quantities can be used to design experiments to confirm or falsify the hypotheses underlying the model and aid in understanding the regulatory properties of the system. The technique is illustrated by an example model, and its predictions are shown to be sensitive to modest structural changes in the network. PMID- 1593900 TI - Towards the molecular bases of polymerase dynamics. AB - One aspect of the strong relationship that is known to exist between the processes of DNA replication and transcription is manifest in the coupling of the rates of movement of the replication fork (rf) and RNA polymerase (rt). We address two issues concerning the largely unexplored area of polymerase dynamics: (i) The validity of an approximate kinematic formula linking rf and rt suggested by experiments in which transcription is inhibited in some prokaryotes with the antibiotic streptolydigin, and (ii) What are the molecular bases of the kinematic formula? An analysis of the available data suggests possible molecular bases for polymerase dynamics. In particular, we are led to a hypothesis: In active chromatin rt may depend on the length (lambda t) of the transcript of the primary messenger RNA (pre-mRNA). This new effect is subject to experimental verification. We discuss possible experiments that may be performed in order to test this prediction. PMID- 1593901 TI - Prognostic significance of the balanced t(1;19) and unbalanced der(19)t(1;19) translocations in acute lymphoblastic leukemia. AB - The recurring chromosomal 1;19 translocation in acute lymphoblastic leukemia (ALL) occurs in balanced t(1;19) (q23;p13) and unbalanced, -19, +der(19)t(1;19)(q23;p13) forms. The clinical features and outcome were compared for 30 patients with the t(1;19) and 36 patients with the der(19) forms. These were 45 children (less than 1-14 years) and 21 adults (15-54 years) (median age 9.0 years), 41 females, 25 males, with median white blood count (WBC) 20.9 x 10(9)/1. Patients were classified by karyotype thus: t(1;19) 11 cases; t(1;19) with additional change (+A) 19 cases; der(19) 17 cases; and der(19) +A, 19 cases. Non-random additional structural abnormalities included involvement of 1q, 6q, i(7q), i(9q), 9p, and 13q. The only significant difference in clinical or blast cell features between patients with the t(1;19) and the der(19) was the greater age of adults with t(1;19) (p less than 0.05). Projected median event-free survival and survival of all cases together was 22 months and greater than 112 months respectively. Neither age nor WBC contributed significantly to prognosis. For patients at all ages, prognosis of der(19) was better than t(1;19). This was statistically significant for event-free and overall survival in childhood (p = 0.02 and p = 0.01 respectively) and was independent of age (p = 0.04 and p = 0.008 respectively) and WBC (p = 0.03 and p = 0.04 respectively). Future studies should examine separately the outcome for patients with the balanced and unbalanced forms of the t(1;19). PMID- 1593902 TI - Adenosine deaminase and purine nucleoside phosphorylase in childhood lymphoblastic leukemia: relation with differentiation stage, in vitro drug resistance and clinical prognosis. AB - Many reports have described the relationship of adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) activities with the immunological subclasses of acute lymphoblastic leukemia (ALL). The clinical significance of these enzymes in leukemias is not yet completely understood. We performed a study in 83 children with untreated ALL to establish the relationships of ADA and PNP to clinical outcome, in vitro drug resistance and differentiation stage of B-cell lineage ALL. ADA and PNP activities were determined radiochemically. In vitro resistance to 6-thioguanine (6-TG) was determined with the MTT assay. ADA activity was not different between proB- and cALL cases but decreased in the sequential differentiation stages cALL----preB-ALL----B-ALL. The PNP level was not different between the four stages of B-lineage ALL. Patients with cALL/preB ALL with low ADA activities had a significantly poorer probability of survival (p = 0.005) than patients with high ADA levels. Patients with cALL/preB ALL with low PNP activities showed a non-significant trend for a poorer prognosis (0.05 less than p less than 0.10) than patients with a high PNP level. Low ADA and PNP activities were not related to in vitro resistance to 6-TG. We conclude that ADA decreases and PNP remains constant in sequential differentiation stages of B lineage ALL. Patients with precursor B-lineage ALL with low activities of ADA have a poorer prognosis than those with high activities of these enzymes. No relationship could be detected between ADA or PNP activity and resistance to 6 TG. PMID- 1593903 TI - Inversion of chromosome 16 and dysplastic eosinophils in accelerated phase of chronic myeloid leukemia. AB - Abnormalities of chromosome 16, including inv(16)(p13q22), del(16)(q22), and t(16;16)(p13;q22), have been reported almost exclusively in association with acute myelomonocytic leukemia and are characteristically accompanied by abnormal eosinophils with dysplastic granules in the bone marrow. We observed an inv(16)(p13q22) in two patients with typical Philadelphia chromosome positive chronic myeloid leukemia (CML). The appearance of the abnormality of chromosome 16 was associated with acceleration of disease or onset of blast crisis and with the appearance in the bone marrow of abnormal eosinophils. In both cases the marrow karyotypes were 46,XY,t(9;22)(q34;q11)/46,XY,inv(16)(p13q22),t(9;22)(q34;q11). In these two patients the temporal association of the acquisition of the inversion 16 and the appearance of monocytoid cells and dysplastic eosinophils in the bone marrow further supports the relationship of this karyotypic abnormality with leukemic monocytoid and eosinophilic evolution. This secondary cytogenetic change appears to be an infrequent manifestation of specific phenotypic disease progression in CML. PMID- 1593904 TI - Absence in Ph-negative, M-BCR rearrangement-positive chronic myelogenous leukemia of linkage between 5' ABL and 3' M-BCR sequences in Philadelphia translocation. AB - The Philadelphia (Ph) chromosome can be detected in the vast majority of patients with chronic myelogenous leukemia (CML). We performed a long-range analysis of chromosomal translocation junction by pulsed-field gel electrophoresis (PFGE) techniques, to examine whether molecular evidence of a reciprocal Ph translocation exists in Ph-positive CML as well as Ph-negative, M-BCR rearrangement-positive CML. The rearrangement within M-BCR and ABL was detected in all patients including nine Ph-positive CML, and three Ph-negative CML. The rearranged 3'-abl fragments showed comigration with rearranged 5'-bcr fragment in rare-cutting restriction enzyme digests in all patients with Ph-positive CML. Thus, the physical linkage of the 3' part of ABL to the 5' side of M-BCR on 22q chromosome was shown. The same linkage was also demonstrated in all three patients with Ph-negative CML. Meanwhile, the rearranged 3'-bcr fragments showed comigration with rearranged pHabl5' (or T39-1-2) fragments in all patients with Ph-positive CML, indicating the linkage of the 5' end of ABL to the 3' part of M BCR on 9q+ chromosome. However, this linkage was absent in two Ph-negative CML patients who could be studied. The results suggest that a genomic insertion of 3' ABL into M-BCR in Ph-negative CML occurs by a single cytogenetic event rather than a two-translocation mechanism. PMID- 1593905 TI - Routine bone marrow punctures during remission of acute myelogenous leukemia. AB - To determine whether serial examinations of the peripheral blood can replace regular bone marrow punctures in the diagnosis of a relapse of acute myelogenous leukemia (AML), the peripheral blood of 40 AML patients in remission undergoing regular bone marrow punctures was studied. Within three months prior to bone marrow examination proving relapse in 97% of the relapses, at least one of the following values of the peripheral blood was pathological: blasts (84%), neutrophil granulocytes (72%), thrombocytes (64%), and hemoglobin (58%). The simultaneous appearance of abnormalities in the peripheral blood and the bone marrow occurs in such high incidence that routine bone marrow punctures are rendered obsolete in the follow-up of AML patients. Needless pain and anxiety can therefore be avoided for many AML patients. PMID- 1593906 TI - Lineage-specific methylation of the c-fms gene in blood cells and macrophages. AB - DNA methylation belongs to the multilevel genetic control system regulating differentiation processes and gene expression. The extent to which DNA methylation contributes to the differentiation of hematopoietic cells is elusive. In the present study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and tissue macrophages. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, whereas constant differences were found between granulocytes and monocytes from the same donor. The second intron of the c-fms gene contains several CpG loci which were found to be hypomethylated on both alleles in monocytes and tissue macrophages. By contrast, these positions were methylated in granulocytes and lymphocytes that did not express the c-fms gene. In comparison to monocytes alveolar and peritoneal macrophages revealed an enhanced demethylation. There were constant differences in c-fms gene methylation between alveolar and peritoneal macrophages with a higher degree of demethylation in alveolar macrophages. We conclude that c-fms gene demethylation is involved in the differentiation of monocytes and macrophages from immature precursors and that the demethylation of lineage-specific growth factor receptor genes might provide an important step in lineage commitment of hematopoietic cells. PMID- 1593907 TI - Selective regulation by hydrocortisone of induction of in vivo differentiation of myeloid leukemic cells with granulocyte-macrophage colony-stimulating factor, interleukin 6 and interleukin 1 alpha. AB - Clones of myeloid leukemic cells can differ in their ability to be induced to differentiate in vitro by different cytokines. Using such leukemic clones, we studied the regulation by hydrocortisone of induction of in vivo differentiation by injection of recombinant interleukin 6 (IL-6), interleukin 1 alpha (IL-1 alpha), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Injection of IL-6 and IL-1 alpha induced in vivo differentiation of leukemic cells that were induced to differentiate by these cytokines in vitro, but not of leukemic cells that were not susceptible to these cytokines in vitro. In contrast, injection of GM-CSF induced in vivo differentiation both in leukemic cells that were susceptible or not susceptible to GM-CSF in vitro. The effect of GM-CSF, but not of IL-6 or IL-1 alpha, on inducing differentiation in vivo was inhibited by pretreatment with hydrocortisone. In leukemic cells that were not induced to differentiate with GM-CSF in vitro, this inhibition of differentiation by pretreatment with hydrocortisone was greater than inhibition of differentiation obtained by pretreatment with cyclophosphamide or irradiation or the use of nude mice. After hydrocortisone pretreatment, the number of peritoneal cells and their ability to produce GM-CSF and IL-6 were suppressed. It is suggested that hydrocortisone can inhibit the effect of an injected cytokine such as GM-CSF on induction of in vivo differentiation of leukemic cells by inhibiting the ability of host cells to produce cytokines to which the leukemic cells are susceptible. PMID- 1593908 TI - Effect of a combined exposure to cytosine arabinoside, bryostatin 1, and recombinant granulocyte-macrophage colony-stimulating factor on the clonogenic growth in vitro of normal and leukemic human hematopoietic progenitor cells. AB - We have examined the effect of a combined 24 h exposure to cytosine arabinoside (ara-C) and the protein kinase C activator bryostatin 1, either alone or in conjunction with recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF), on the clonogenic growth of 14 primary samples from acute myelogenous leukemia (AML) patients, as well as normal human committed and early hematopoietic progenitors. Incubation of blasts with 1 microM ara-C and 12.5 nM bryostatin 1(+/- 1.25 ng/ml rGM-CSF) resulted in a heterogeneous pattern of inhibitory effects toward primary leukemic colonies, ranging from 32-98%, and subadditive to synergistic drug interactions. However, exposure of blasts to ara C and bryostatin 1, either with or without rGM-CSF, eliminated leukemic cell self renewal in 80-93% of samples, and very substantially reduced growth in the remainder. Exposure of normal human bone marrow mononuclear cells to identical concentrations of ara-C and byostatin 1 permitted the survival of 23% of committed myeloid progenitors (granulocyte-macrophage colony-forming units), and greater than 50% when rGM-CSF was included. Finally, exposure of bone marrow populations highly enriched for progenitor cells (CD34+, DR-, CD71-) to ara-C and bryostatin 1 +/- rGM-CSF for 24 h led to minimal reductions (e.g. 10-15%) in the survival of early hematopoietic progenitors (high proliferative potential colony forming cells). Together, these findings indicate that combined exposure in vitro to ara-C and bryostatin 1, both with and without rGM-CSF, effectively inhibits the growth of leukemic cells with self-renewal capacity, while sparing a significant fraction of normal committed and primitive hematopoietic progenitors. PMID- 1593909 TI - Effects of mitoxantrone in combination with other anticancer agents on a human leukemia cell line. AB - To investigate the effects of mitoxantrone in combination with other anticancer agents, a human T-cell leukemia cell line, MOLT-3, was incubated for 3 days in the presence of two drugs (mitoxantrone and the combined drug) and cell growth inhibition was determined by assay with 3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazonium bromide. The effects of drug combinations at doses giving 80% inhibition (ID80) were analyzed by an improved isobologram method. A supra additive (synergistic) effect was observed for mitoxantrone in combination with amsacrine, cisplatin, or cytosine arabinoside. An additive effect was observed for its combination with bleomycin, doxorubicin, etoposide, 5-fluorouracil, mitomycin C, 6-mercaptopurine, or vincristine. A sub-additive (antagonistic) effect was observed for its combination with methotrexate. These data suggest that mitoxantrone, administered simultaneously with any one of a majority of anticancer agents we studied, is advantageous for cytokilling. Of the anticancer agents tested, amsacrine, cisplatin, and cytosine arabinoside are the most suitable for combination with mitoxantrone, and these combinations are worthy of clinical investigation. Methotrexate in our system is inappropriate for simultaneous administration with mitoxantrone. These data should provide useful information for the establishment of clinical protocols involving mitoxantrone. PMID- 1593911 TI - Polymerase chain reaction analysis of BCR-ABL sequences in adult Philadelphia chromosome-negative acute lymphoblastic leukemia patients. AB - The Philadelphia (Ph) translocation is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL) and is associated with an adverse prognosis. Using polymerase chain reaction (PCR) technology we recently observed a remarkably high incidence (55%) of BCR-ABL rearrangements in adult common ALL patients. In the present study we asked whether a subset of Ph-negative cALL, similarly to Ph-negative chronic myelocytic leukemia (CML) patients, exhibit BCR ABL transcripts. PCR analysis of 58 adult Ph-negative cALL patients, including 47 cases with a normal karyotype revealed no evidence of chimeric BCR-ABL genes. We conclude that Ph-negative BCR/ABL-positive ALL is very rare entity if existing at all. PMID- 1593910 TI - Expression and regulation of the evi-1 gene in the human factor-dependent leukemia cell line, UCSD/AML1. AB - The human factor-dependent leukemia cell line UCSD/AML1 contains the t(3;3) (q21;q26) characteristic of the syndrome of acute leukemia with high platelets. The human homologue of the murine leukemia oncogene evi-1 was recently localized to chromosome 3q24-3q28 and transcription of evi-1 is a frequent event in mouse retrovirus-induced leukemias (17). To determine whether translocations near human 3q24 might induce similar genetic changes, we examined and compared evi-1 and c myc expression and regulation in UCSD/AML1 cells. Steady-state evi-1 transcripts were detected in UCSD/AML1 and murine leukemia M1 cells, but were not present in HL60 or Namalwa human leukemia cells. Transcription assays showed the evi-1 gene was actively transcribed in UCSD/AML1, but not HL60 nuclei. Evi-1 transcript sizes and half-life were similar in UCSD/AML1 and human HEC-1B carcinoma cells which express evi-1 transcripts, but do not have abnormalities involving chromosome 3. An alternative splice site detected by polymerase chain reaction was present in transcripts from both cell lines. Regulation of evi-1 RNA in UCSD/AML1 cells was similar to that of actin transcripts in response to cycloheximide or phorbol-ester-induced macrophage differentiation. After withdrawal of granulocyte/macrophage colony-stimulating factor (GM-CSF), evi-1, actin, and histone H3 transcripts declined in concert with exit from the cell cycle. Minor differences in rates of recovery were noted for these three genes after GM-CSF restimulation. In contrast, c-myc was expressed at high levels in UCSD/AML1 cells and showed evidence for specific regulation in response to cycloheximide, phorbol ester, and GM-CSF withdrawal and restimulation. These studies suggest the 3q translocation in UCSD/AML1 cells is associated with evi-1 transcription and expression of a potential transforming gene. In contrast to c myc, evi-1 expression is minimally altered by biologically active chemicals or growth factor stimulation. PMID- 1593912 TI - A controversy. Nucleoside transporter expression is correlated with proliferative rate in acute myeloid leukemia. PMID- 1593913 TI - A comment on the Duke University Center Health Profile. PMID- 1593914 TI - The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. AB - A 36-item short-form (SF-36) was constructed to survey health status in the Medical Outcomes Study. The SF-36 was designed for use in clinical practice and research, health policy evaluations, and general population surveys. The SF-36 includes one multi-item scale that assesses eight health concepts: 1) limitations in physical activities because of health problems; 2) limitations in social activities because of physical or emotional problems; 3) limitations in usual role activities because of physical health problems; 4) bodily pain; 5) general mental health (psychological distress and well-being); 6) limitations in usual role activities because of emotional problems; 7) vitality (energy and fatigue); and 8) general health perceptions. The survey was constructed for self administration by persons 14 years of age and older, and for administration by a trained interviewer in person or by telephone. The history of the development of the SF-36, the origin of specific items, and the logic underlying their selection are summarized. The content and features of the SF-36 are compared with the 20 item Medical Outcomes Study short-form. PMID- 1593915 TI - Can small-area analysis detect variation in surgery rates? The power of small area variation analysis. AB - A variety of statistical methods can be used in small-area analysis to test whether there is more variation than would be expected by chance alone. However, the power of these methods to detect existing variation has never been studied. The authors used data regarding back surgery in Washington State to suggest several types of variation that might exist (alternative hypotheses), and then used computer simulation to determine the power, or the probability of detecting this variation. The chi-square test had the highest power of all methods considered against most alternative hypotheses. Power is higher if there are no multiple admissions, rates are higher, and counties have larger or similar population size. Problems of accounting for multiple admissions, adjustment for age and sex, choosing the optimum size of small areas, and detection of outliers also are discussed. PMID- 1593916 TI - Community pharmacists as immunization advocates. Cost-effectiveness of a cue to influenza vaccination. AB - To assess the cost-effectiveness of a cue to influenza vaccination provided by community pharmacists, a decision tree was constructed of the consequences of implementing a pharmacy-based vaccine-advocacy program, based on experience gained in an experiment involving three community pharmacies in Durham County, North Carolina. The model used morbidity and mortality assumptions derived from the infectious-disease literature and cost assumptions based on 1990-91 Medicare Part A and Part B reimbursement costs. This analysis suggests that if Medicare reimbursed pharmacists for advising 100,000 patients at risk to accept influenza vaccine through vaccine-advocacy messages, for an apparent expenditure of $110,000, the increased rate of influenza vaccinations would avert 139 hospitalizations and 63 deaths, and actually yield Medicare a net savings of $280,588. These calculations probably underestimate the benefit to society of a pharmacy-based vaccine-advocacy program, because only direct costs to the single government agency were computed and no cost was attributed to death or lost earnings. PMID- 1593917 TI - Assessing physicians' compliance with guidelines for Papanicolaou testing. AB - In this study, population-based data were used to examine the appropriateness of Papanicolaou (Pap) testing from the perspective of the women being tested and their physicians. The approach used is unique in its assessment of overtesting and undertesting in the primary care setting. From the data base of the province of Manitoba's universal health insurance plan, 4-year health histories (1981 to 1984) were constructed for each woman from a random sample of the population of women who, in 1982, were between the ages of 25 to 64 years (n = 22,287). At the last visit to a general practitioner, gynecologist, or general surgeon in 1984 (termed the current visit), the authors determined whether a Pap test was given for each woman. Using decision rules from a Canadian task force report on cervical screening and previous health history, the authors evaluated the appropriateness of screening by determining whether a Pap test was given and was needed, or whether a women who had not received a Pap test required one. Overall, 55.7% of women were tested appropriately. Of the 5352 women who received a Pap test at the current visit, 62.8% were overtested. Of the 16,935 women not tested at the current visit, 38.5% required screening (i.e. were undertested). Characteristics of a physician's practice that were significantly related to compliance with the guidelines included having a high proportion of patients visiting for obstetric or gynecologic reasons. Variables that were associated with negative compliance were 1) being a gynecologist; and 2) having a high proportion of patients who lived in inner city or rural areas. Because physicians are paid a fee for every Pap smear taken and the guidelines were well disseminated, these results should be reasonably representative of fee-for service practice in North America, where preventive care is not subject to user charges. This study supports previous findings that a passive approach to dissemination of guidelines is insufficient to effect practice. PMID- 1593918 TI - The cesarean decision in New York State, 1986. Economic and noneconomic aspects. AB - This study describes a research project involving economic and noneconomic aspects of the cesarean decision. The study was based on a 1986 data set dealing with 68,847 obstetric deliveries in New York State excluding New York City, and had the largest number of variables known to have been assembled to analyze the cesarean decision. The authors estimated a probit multiple regression in which the dependent variable was the method of delivery. The results diverge from widely held beliefs and research findings in some areas, and are of considerable interest in other areas. Contrary to other findings, the authors did not find a relationship between date of graduation from medical school and the probability of a cesarean section. More importantly, the authors failed to find much support for the idea that obstetricians perform cesareans to enrich themselves from the additional free income. However, our findings are consistent with the idea that obstetricians occasionally perform cesarean sections to manage their time, which does represent a form of economic self-interest. The study developed a proxy measure for fear of malpractice and found a negative relationship between fear of malpractice and cesarean section use. Finally, county cesarean rate and adjusted hospital cesarean section rate strongly and significantly influenced the probability that a given delivery is performed by cesarean section. PMID- 1593919 TI - The effects of psychological distress and psychological well-being on use of medical services. AB - In this study, the authors determined whether mental health status affects the use of general medical services, with and without adjustment for the correlated effects of general health perceptions and physical health status on such use. Data were used from the RAND Health Insurance Experiment, which has information on up to 5 years of use of medical services by a nonelderly, civilian, general population. Health status and other covariates were assessed by self-administered questionnaires at enrollment. In the absence of statistical control for general and physical health status, worse mental health status-whether assessed by a global self-report measure or its two component parts, psychological well-being and psychological distress-significantly increased the use of both inpatient and outpatient general medical services. After controlling for general health perceptions, physical health status, demographic factors, and insurance plan coverage, the effects of mental health status on use are reduced, but not eliminated. Psychological distress and psychological well-being retained independent effects on total medical expenses. PMID- 1593920 TI - Effects of military experience on mental health problems and work behavior. PMID- 1593921 TI - Inhibition of [3H]dopamine uptake into rat striatal slices by quaternary N methylated nicotine metabolites. AB - The effects of quaternary N-methylated nicotine derivatives were examined on in vitro uptake of [3H]dopamine ([3H]DA) in rat striatal slices. Striatal slices were incubated with a 10 microM concentration of the following compounds: N methylnicotinium, N-methylnornicotinium, N-methylcotininium, N,N' dimethylnicotinium and N'-methylnicotinium salts. The results clearly indicated that significant (60%) inhibition of [3H]DA uptake occurred with those compounds possessing a N-methylpyridinium group; whereas, compounds that were methylated at the N'-pyrrolidinium position were less effective or exhibited no inhibition of [3H]DA uptake. The results suggest that high concentrations of quaternary N methylated nicotine metabolites which are structurally related to the neurotoxin MPP+, and which may be formed in the CNS, may protect against Parkinson's Disease and explain the inverse relationship between smoking and Parkinsonism reported in epidemiologic studies. PMID- 1593922 TI - Inhibition of estradiol-induced early osteoarthritic changes by tamoxifen. AB - Previous studies on osteoarthritic changes induced by intraarticular injections of estradiol benzoate (EB) suggest estrogen as a risk factor in the development of knee osteoarthritis (OA). The present study observed the anti-arthritic effects of tamoxifen (TMX). Oophorectomized rabbits were subjected to intraarticular injections of vehicle control, EB, TMX, or EB/TMX for 3 weeks. The cartilage changes were assessed by light and scanning electron microscopic examination, enzyme histochemical analysis, and the amount of alcian blue stain binding to glycosaminoglycans. EB injections resulted in cell necrosis, chondrocyte clonings, and pittings, whereas the vehicle control, TMX, and EB/TMX injected groups showed no histologic abnormalities. Histochemical analysis showed that the numbers of lactate dehydrogenase (LDH)-reactive chondrocytes in the EB injected group were significantly reduced when compared to other groups (p less than 0.001). The injections of EB/TMX significantly reduced the chondrocyte numbers in the lateral superficial layer (p less than 0.05), compared with the vehicle injection. TMX-injected group revealed slight although insignificant decreases in chondrocyte numbers. The amount of alcian blue stains, representing the relative amount of proteoglycans, significantly decreased only in the superficial layer of the EB- and EB/TMX-injected groups (p less than 0.05). TMX, when concurrently injected with EB, antagonized the chondrodestructive effects of estradiol at the early stage of knee OA in rabbits. The results suggest the potential therapeutic use of TMX at the early stage of OA. PMID- 1593924 TI - Failure of d-cycloserine to reverse cognitive disruption induced by scopolamine or phencyclidine in primates. AB - The partial glycine agonist d-cycloserine may be of therapeutic use as a cognitive enhancer. We examined the ability of d-cycloserine (3-14 mg/kg i.m.) to reverse cognitive impairments induced by scopolamine (0.03 mg/kg) or PCP (0.25 mg/kg). There was no evidence for a dose-related improvement in visuospatial memory using retention intervals of 2,10 or 20 sec. A possible explanation for these findings is that central glycine function cannot be adequately increased using systemic administration of d-cycloserine in this dose range. PMID- 1593923 TI - Radioligand binding studies reveal marked species differences in the vasopressin V1 receptor of rat, rhesus and human tissues. AB - The [3H]arginine-vasopressin ([3H]AVP) binding site in rat, rhesus and human liver and nonpregnant human uterus was characterized and contrasted. [3H]AVP bound with high affinity (Ki values, 0.2-0.6 nM) to preparations of all tissues studied. Competition binding studies using a series of compounds from three structural classes indicate a marked species difference between the rat and primate liver AVP-V1 site. This site in rhesus and human liver however, is essentially identical, indicating that the rhesus liver is an appropriate surrogate for human tissue. These studies also indicate that the AVP-V1 site of nonpregnant human uterus and human liver is equivalent. PMID- 1593925 TI - Alanine and hyperosmolarity are responsible for the stimulation of cardiomyocyte glucose transport by samples containing a glucose tolerance factor. AB - Low-molecular-weight, cationic samples, that were previously reported to contain a glucose tolerance factor, were obtained by partial purification from yeast extract. These samples increased the rate of glucose transport in isolated cardiomyocytes 2.0- to 2.5-fold. A further purification by gel filtration led to the separation of two active components that were identified as (i) L-alanine and (ii) an elevated osmolarity. Moreover, the effect of partially purified fractions (before gel filtration) (i) was decreased upon alanine depletion with alanine dehydrogenase and (ii) was mimicked by the additive action of alanine and of a hyperosmolar medium. These findings indicate that the effect of this partially purified material is not accounted for by a putative glucose tolerance factor. Interestingly, alanine elicited its effect at concentrations that correspond to physiological plasma values, which suggests that this amino acid might be involved in the regulation of glucose transport in cardiomyocytes. Furthermore, the effect of alanine was prevented by DL-cycloserine (1 mM) or aminooxyacetate (1 mM), but not by cycloheximide (35 microM), indicating that (a) transamination reaction(s), but not protein synthesis, is required. PMID- 1593926 TI - The ability of (-)deprenyl to increase superoxide dismutase activities in the rat is tissue and brain region selective. AB - In a previous study we have shown that chronic administration of (-)deprenyl increases activities of superoxide dismutase (SOD) and catalase (CAT) in rat striatum (1). The present study attempted to clarify how specific the effect of deprenyl is to certain tissues and brain regions in the rat. Two mg/kg/day of deprenyl was continuously infused s.c. in young male Fischer-344 rats. On the 22nd day, rats were sacrificed and enzyme activities of SOD and CAT were determined in several different brain regions and the liver. Activities of both SOD and CAT were significantly increased in striatum and substantia nigra but not in hippocampus, cerebellum or liver. Both types of SOD (i.e. Cu Zn-SOD and Mn SOD) were significantly increased in striatum, substantia nigra. Interestingly, in cerebral cortices of three different regions, activities also tended to increase (especially those of Mn-SOD), although the increase was not so striking as in substantia nigra and striatum. The results confirm the previous observation that (-)deprenyl can increase free radical scavenger enzyme activities in striatum and provide further evidence that this effect is selective to certain brain regions and tissue types. PMID- 1593928 TI - A rabbit antiserum raised against the hexapeptide endothelin(16-21) shows different binding affinities for endothelin-1, -2 and -3. AB - A antiserum raised against the C-terminal hexapeptide ET16-21 common to ET-1, -2 and -3 was produced and characterized with respect to its binding properties for ET-1, -2, -3, ET16-21, the C-terminal octapeptide ET14-21, its derivative Phe21 ET14-21 and human big-ET-1. The antibody reacted with the peptides with decreasing binding affinities in the order: ET-1 greater than ET-2 greater than or equal to ET16-21 = ET 14-21 much greater than Phe21-ET14-21. It showed no crossreactivity with human big-ET-1. Similar results were obtained using [125I]ET 1, -2 or -3 as tracer. Substitution of Trp21 by Phe decreased the binding affinity of ET14-21 about 10 fold. Thus, the immunologically recognized sequence of the peptides is C-terminal and Trp21 seems to be important for high binding affinities. The significant differences in binding affinity observed for ET-1, 2, -3 and ET16-21 are consistent with an interaction of the C-terminal part of the endothelins with the bicyclic N-terminal part. PMID- 1593927 TI - Changes in muscarinic acetylcholine receptors in the isolated duodenum from repeatedly cold-stressed rats and the effect of neurotropin. AB - In rats repeatedly cold-stressed by specific alternation of rhythm in environmental temperature (SART-stressed rats), the contractile response to acetylcholine (ACh) of the isolated duodenum was remarkably decreased, whereas the contractile responses to K+, Ba2+ and Ca2+ were comparable to those in non stressed rats. The amount of [3H]quinuclidinyl benzilate in the duodenum of SART stressed rats was about 50% of that in non-stressed rats, but the KD value remained unchanged. Long-term administration of hexamethonium prevented the changes in SART-stressed rats. The daily treatment with Neurotropin, an extract isolated from inflamed rabbit dermis inoculated with vaccinia virus, dose dependently prevented the changes in SART-stressed rats. However, Neurotropin had no effect on the ACh-induced decrease in muscarinic ACh receptor (m-ACh.R) in cultured vas deferens of guinea pig. These results suggest that down-regulation of m-ACh.R in duodenum by SART stress may be associated with enhanced activity in the parasympathetic center. Moreover, Neurotropin is thought to prevent the down regulation of m-ACh.R throughout the central nervous system. PMID- 1593929 TI - Neurotensin-induced activation of hypothalamic dopaminergic neurons is accompanied by a decrease in pituitary secretion of prolactin and alpha melanocyte-stimulating hormone. AB - The effects of neurotensin on the activity of hypothalamic tuberoinfundibular and periventricular-hypophysial dopaminergic (DA) neurons, and on the secretion of pituitary hormones that are tonically regulated by these neurons (i.e. prolactin and alpha-melanocyte-stimulating hormone [alpha MSH], respectively) were examined in estrogen-primed ovariectomized rats. The activity of tuberoinfundibular and periventricular-hypophysial DA neurons was estimated by measuring concentrations of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the terminals of these neurons in the median eminence and intermediate lobe of the posterior pituitary, respectively. Intracerebroventricular administration of neurotensin caused a dose- and time-related increase in DOPAC concentrations in both the median eminence and intermediate lobe, and a concurrent decrease in plasma levels of prolactin and alpha MSH. These results suggest that neurotensin induced inhibition of secretion of prolactin and alpha MSH from the pituitary may be due to the stimulatory action of this neuropeptide on the release of dopamine from tuberoinfundibular and periventricular-hypophysial neurons. PMID- 1593930 TI - Measurement of inducible proteins improves the precision of the local pigeon crop sac bioassay for prolactin. AB - The pigeon crop-sac is a well-known target organ of prolactin (PRL). Pukac and Horseman (Endocrinology 114: 1718, 1984) reported that injections of the hormone caused changes in the expression of several specific proteins in that organ. We investigated the possibility that measuring the amounts of three of these proteins might improve the precision of the local pigeon crop-sac assay for PRL. Pigeons were given four injections of phosphate-buffered saline or different doses of ovine (o) PRL for 2 days and were killed on day 3. The DNA and total protein content of their crop-sac mucosal epithelial cells were measured and a supernatant of homogenized epithelial cells was processed by SDS-PAGE. The amounts of the three specific proteins in the stained gels were measured by densitometry. Treatment with oPRL increased the concentration of two of these proteins in the crop mucosal tissue (CP 14 and CP 25) and decreased that of the third one (CP 17). Measurement of total protein or of changes in the individual protein bands gave dose-response relationships with poor indices of precision (lambda greater than 0.3). Measurement of DNA content gave an assay endpoint with a reasonably good lambda value (0.16) but when the changes in the amounts of CP 14 and CP 25 were expressed as ratios to the changes occurring in CP 17, very precise assay endpoints (lambda = 0.06-0.08) were obtained. PMID- 1593931 TI - Hospice care--reflections of a maternity nurse. PMID- 1593932 TI - An enigmatic title? PMID- 1593933 TI - Inhaled steroids for children with asthma. PMID- 1593934 TI - Clinical excellence and cross-training. PMID- 1593935 TI - Curran v. Bosze: bone marrow donation. PMID- 1593936 TI - Adjustments to breast-feeding. PMID- 1593937 TI - MCN spotlight. Care maps. PMID- 1593938 TI - Periventricular-intraventricular hemorrhage in the newborn. PMID- 1593939 TI - Humor in postpartum education: depicting a new mother's worst nightmare. PMID- 1593940 TI - Nursing interventions for thromboembolic complications of chronic ulcerative colitis in children. PMID- 1593942 TI - Administration and scoring: test users' responsibilities and test takers' rights. PMID- 1593943 TI - The illiterate client. PMID- 1593941 TI - Helping patients choose an appropriate method of birth control. PMID- 1593944 TI - Cu/Zn superoxide dismutase mRNA and enzyme activity, and susceptibility to lipid peroxidation, increases with aging in murine brains. AB - To protect against reactive oxygen species, prokaryotic and eukaryotic cells have developed an antioxidant defence mechanism where O2- is converted to H2O2 by superoxide dismutase (Sod), and in a second step, H2O2 is converted to H2O by catalase (Cat) and/or glutathione peroxidase (Gpx). If Sod levels are increased without a concomitant Gpx increase, then the intermediate H2O2 accumulates. This intermediate could undergo the Fenton's reaction, generating hydroxyl radicals which may lead to lipid peroxidation in cells. In this study, we investigate the expression of Sod1, Gpx1 and susceptibility to lipid peroxidation during the aging process in mouse brains. We demonstrate that the mRNA levels and enzyme activity of Sod1 are higher in brains from adult mice compared to neonatal mice. Furthermore, we show that a linear increase in Sod1 mRNA and enzyme activity occurs with aging (1-100 weeks). On the contrary, we find that the mRNA and enzyme activity for Gpx1 does not increase with aging in mouse brains. In addition, our results demonstrate that the susceptibility of murine brains to lipid peroxidation increases with aging. The data in this study are consistent with the notion that reactive oxygen species may contribute to the aging process in mammalian brains. These results are discussed in relation to the normal aging process in mammals, and to the premature aging and mental retardation in Down syndrome. PMID- 1593945 TI - Direct imaging of magnetic field gradients by group spin-echo selection. AB - A new image processing method for single-echo gradient echo imaging is presented which extracts local phase gradient information by k-space filtering instead of by phased reconstruction and spatial differentiation. It is shown that local phase gradient directions and semiquantitative local phase gradient magnitudes can be directly measured, even in regions where phased image reconstruction suffers from multiple phase foldovers due to strong phase modulations. The directional information thus obtained can be used as a reference to identify and correct phase modulation foldovers in phase maps which may be computed from the same raw data. The method is applied here to measure static magnetic field gradients and illustrates fundamental k-space signal properties of gradient echo imaging. Based on this concept, image artifacts caused by conventional strong k space filtering in gradient echo imaging are discussed. PMID- 1593946 TI - Selective suppression of lipid resonances by lipid-soluble nitroxides in NMR spectroscopy. AB - The ability of lipid-soluble nitroxides to suppress selectively the peaks of lipid resonances in 31P, 1H, and 13C NMR spectra was investigated in serum as part of studies aimed at using these contrast agents for magnetic resonance imaging and magnetic resonance spectroscopy in vivo. Nitroxides are especially interesting potential contrast agents because they can reversibly be converted in cells to diamagnetic hydroxylamines, with conversion rates that are dependent on the redox potential and the intracellular concentration of oxygen; the characterization of nitroxide-dependent changes in NMR spectra may therefore be a useful means to measure oxygen-dependent redox metabolism in vivo. The fatty acid analogs, doxyl stearates, suppressed the methyl resonance of choline and the methyl and methylene peaks of lipids in the 1H NMR spectra of serum samples. As a consequence, lactate peaks, which were not readily detected became clearly resolved and could be evaluated quantitatively. The 31P resonance of phosphatidylcholine in the 31P NMR spectrum was suppressed by 5-doxyl stearate and 4-(N,N-dimethyl-N-hexadecyl)ammonium-2,2,6,6-tetramethylpiperidine-1-oxy l,iodid e (Cat16). In the 13C NMR spectrum, the resonances of the methyl groups of choline and the lipids also were broadened significantly by addition of 5 doxyl stearate. Differential suppression of lipid resonances can be employed to facilitate quantitation of lactate. PMID- 1593947 TI - Twisting radial lines with application to robust magnetic resonance imaging of irregular flow. AB - A problem with magnetic resonance angiograms of vessels containing irregular flow is that flow-induced dephasing can result in voids in the image. These void regions are susceptible to misinterpretation as regions of stenosis or other vessel pathology. Flow-induced dephasing can be minimized by using radial lines to cover k space. However, radial lines provide a very nonuniform, and hence, inefficient, coverage of k space. By twisting the outer portions of the radial trajectories, undistorted images of very rapid and turbulent flow can be obtained with a reasonable number of RF excitations. PMID- 1593948 TI - Analysis of the temporal and spatial dependence of the eddy current fields in a 40-cm bore magnet. AB - Eddy current fields, generated in an animal-size superconducting NMR magnet by a nominally rectangular pulsed transverse gradient applied in the vertical direction, have been studied by measuring the offset frequency of the proton NMR signal obtained from a small spherical sample. Measurements were made, after various time delays, at nine different locations in the sample space. Analysis of the data shows that the time-dependent fields at all nine locations are quite well accounted for by the superposition of only four independent exponentially decaying components that have time constants in the range from 9 to 400 ms. Two of these were found to be caused by eddy currents generated in the magnet structure. They generate primarily linear gradients, though one of them also produces a B0 shift, indicating a significant asymmetry about the isocenter of the conducting structure in which the eddy current flows. The other two exponentially decaying components, which had very different time constants from the eddy currents and also initial amplitudes of the opposite sign, were generated by the preemphasis unit. This calls into question the procedure used to adjust the preemphasis unit and an alternative method is proposed. PMID- 1593949 TI - Intensity artifacts in MRI caused by gradient switching in an animal-size NMR magnet. AB - The switching of magnetic field gradients in MRI gives rise to eddy currents in the structural components of superconducting magnet systems. The associated magnetic fields cause intensity artifacts which are particularly severe in some animal-size systems. We treat theoretically three mechanisms which cause intensity artifacts in one-dimensional projection images obtained by a spin-echo technique. The first is an off-resonance effect, caused by applying the refocusing pulse before the read compensation gradient pulse has decayed sufficiently. The other two mechanisms are caused by a spatial dependence of the phase accumulated by the spins at the time of formation of the echo, as a result of the eddy current fields. First, interference causes a loss of transverse magnetization because of a variation in the phase of spins which lie on the same isochromat during the read gradient pulse. Second, a variation of the phase of the spins in a direction orthogonal to the isochromats causes spins throughout the sample to refocus at different times. These two mechanisms are fundamentally different, since interference can occur even if the main magnetic field is homogeneous, whereas improper refocusing does not. It is shown that there is no loss of intensity by the interference mechanism if phase encoding is used to form two-dimensional images. This may well be a major reason why images obtained by 2DFT have been found to be generally superior to those obtained by projection reconstruction. Experimentally, the distribution of intensity in one-dimensional projection images of a square slice phantom is compared with theoretical intensities, estimated using eddy current field reported in the preceding paper. PMID- 1593950 TI - Water-suppressed one-dimensional 1H NMR spectroscopic imaging of myocardial metabolites in vivo. AB - Excitation by conventional B1 pulses in surface coil chemical-shift imaging experiments yields resonance intensities that vary greatly with position. B1 compensated semi-selective pulses overcome much of this problem. These pulses are employed for excitation and refocusing in 1H NMR spectroscopic localization in the intact heart. PMID- 1593951 TI - Decrease of glucose in the human visual cortex during photic stimulation. AB - Localized proton NMR spectroscopy was used to study cerebral metabolism in the visual cortex of healthy adults during rest and photic stimulation. Basal lactate levels showed considerable interindividual differences ranging from below detectability (less than 0.3 mM) to about 1 mM without consistent alteration during photic stimulation. Local brain glucose levels were significantly reduced (approximately 50%) during the entire period of photic stimulation and recovered to resting levels (approximately 0.8 mM) within 10 min after the end of stimulation. This decrease reflects the establishment of a new equilibrium due to enhanced delivery (blood flow) and enhanced consumption. The absence of lactate accumulation supports the hypothesis of a rapid efflux of lactate from brain tissue under activated conditions. PMID- 1593952 TI - Improved efficiency in 2DFT magnetization-prepared rapid gradient echo imaging: application to abdominal imaging. AB - The incorporation of the phase offset multi planar (POMP) technique into breathheld magnetization-prepared gradient echo imaging is discussed as a means for improving imaging efficiency without sacrificing resolution, contrast, or SNR improvement. The phase encoding order necessary to preserve the centric approach is described. When combined with interleaving, the POMP technique enables four 256 x 256 images to be acquired in a 12-s breathhold, doubling the efficiency of the original technique. This scan efficiency is compared with that of other T1 weighted 2DFT methods. PMID- 1593953 TI - Localized 13C NMR spectroscopy of myo-inositol in the human brain in vivo. AB - Natural abundance 13C NMR spectra obtained from 144-cm3 volumes in the human brain contained well-resolved resonances of myo-inositol after 60 min of data accumulation. A mean concentration of 7.2 +/- 0.5 mumol/g (+/- SE, n = 7) was calculated from the comparison with phantoms. 13C NMR spectroscopy thus provides a complementary role in the quantitation of metabolites also observed in the crowded 1H spectrum. PMID- 1593954 TI - Noninvasive determination of regional cerebral blood flow in rats using dynamic imaging with Gd(DTPA) PMID- 1593955 TI - 31P MRS as an early prognostic indicator of patient response to chemotherapy. AB - In this study 31P spectral changes were closely monitored following the initial administration of cytotoxic drugs and related to five parameters of patient response. Pre- and postchemotherapy 31P MRS examinations were performed on 16 patients with large, malignant tumors. These included four tumor types: (i) lymphoma (n = 7), (ii) breast carcinoma (n = 4), (iii) musculoskeletal tumors (n = 4), and (iv) adenocarcinoma (n = 1). A mean of 5 spectra/patient (range 2-10) was performed following the initial chemotherapy. The spectral trends exhibited by 14 of 16 patients reached "points of maximum change," after which they began to revert toward prechemotherapy values. In 2 of 16 patients that did not respond to the initial chemotherapy regimen, no spectral trends were observed. The degree of change of certain spectral parameters, namely, decreases in PME, PME/PDE, PME/PCr, PME/NTP, PDE/PCr, and tumor pH, as well as increases in the ratios Pi/PME and Pi/PDE, were associated with good patient response and separated responders from nonresponders. Pi/PME appears the most promising for discriminating partial from complete responders. PMID- 1593956 TI - Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. I. Assessment of absolute metabolite quantification. AB - In a series of three papers, we demonstrate and validate an approach for concurrent absolute quantification in situ of blood flow and energy metabolism with a modification of the NMR method for absolute concentration determination put forth by Thulborn and Ackerman [J. Magn. Reson. 55, 357 (1983)] and later expanded upon by Tofts and Wray. In this first paper of the series, we briefly review the theoretical basis for the concentration measurement and present, for the first time, a successful paired validation of metabolite quantification via 31P surface-coil NMR through corroborative in vitro enzymatic assays. The paired radiolabeled microsphere validation of blood flow measurement via 2H surface-coil NMR employing D2O as a freely diffusible tracer and the concurrent determination of blood flow and energy metabolism in a septic rat model are presented in the accompanying second and third paper to complete the series. In this article a classical RF tank circuit is employed to describe the effect of conductive sample loading on the NMR receiver by considering its apparent series resistance. It is shown in an easily visualized generalizable manner that the effect of sample loading on the observed NMR signal intensity can be accounted for quantitatively by monitoring changes in 90 degrees pulse width at constant power at a fixed reference point, i.e., Ssample = Sphantom (PW90phantom/PW90sample). In a series of paired experiments the absolute concentrations of high energy phosphates obtained from resting rat leg muscle (n = 4) in situ (NMR) and in vitro (enzymatic) were determined as follows: [PCr]NMR = 17.2 +/- 0.8 SD, [PCr]enzymatic = 17.3 +/- 2 SD, [ATP]NMR = 5.1 +/- 0.8 SD, [ATP]enzymatic = 5.0 +/- 0.2 SD mmol/kg tissue wet wt. Results of these two independent methods of concentration determination were not statistically different (P = 0.94 and P = 0.74 respectively) and serve to rigorously validate the Thulborn approach for absolute quantification of phosphorous metabolites in situ via NMR. Furthermore, these results strongly suggest that ATP and PCr in resting rat leg muscle under normal physiologic conditions are 100% NMR visible. The free cytosolic [ADP]NMR was estimated from the creatine kinase reaction equilibrium expression to be 0.022 +/- 0.003 SD mmol/kg tissue wet wt. PMID- 1593957 TI - Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. II. Validation of the deuterium NMR washout method for measuring organ perfusion. AB - The deuterium washout technique of measuring tissue blood flow is based upon NMR detection of HOD (administered as D2O saline, but typically detected as HOD because of rapid proton-deuteron exchange) as a freely diffusible tracer. Though this method is coming into more general use, it has not yet been rigorously validated in vivo against an accepted, independent measure of tissue blood flow. To this end, simultaneous radiolabeled microsphere and HOD washout blood flow measurements were made in rat gastrocnemius muscle. D2O saline was administered either intramuscularly or intraarterially (near the aortic bifurcation), and the sciatic nerve was electrically stimulated to increase the muscle blood flow rate. Over a range of flows of 2 to 80 ml/(100 g.min), comparison of microsphere and HOD washout measurements showed good agreement, with r = 0.92 (n = 16) for intramuscular administration and r = 0.91 (n = 12) for intraarterial administration. These data strongly suggest that the HOD washout technique provides accurate blood flow measurements in skeletal muscle. PMID- 1593958 TI - Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. III. Alterations of muscle blood flow and metabolism during sepsis. AB - In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis. PMID- 1593959 TI - Proton NMR studies on ischemic rat brain tissue. AB - The spin-lattice relaxation time (T1) of water protons and the cross-relaxation time (TIS) between irradiated protein protons and observed water protons were measured in order to study water-macromolecular interactions in ischemic rat brain tissues. Tissues were obtained by bilateral common carotid artery occlusion from stroke-prone spontaneously hypertensive rats. Water, Na, and K contents were measured in ischemic brain tissue at the same time. Water and Na content increased while the TIS value and K content decreased following ischemic insults. The T1 value did not change until 180 min after ischemia had been induced. Changes in the TIS value occurred earlier than changes observed for the T1 value, water, and electrolyte contents. Results indicate that the value of TIS may be useful for detecting cerebral ischemia and that the physical structure of water macromolecular interaction may be altered soon after ischemic onset in brain tissue. PMID- 1593960 TI - Detection of significant features and statistical analysis of 2D and 3D images of 31P metabolites. AB - The application of spectroscopy techniques to the study of normal and pathological tissue is currently limited by the difficulties of acquiring precisely localized spectra and analyzing the resulting, relatively low signal-to noise data. Interpretation of multivoxel spectroscopy data is greatly facilitated by estimating peak parameters and representing their spatial distribution as metabolite images. We present here the new algorithm MIMSTATS, which performs an analysis of these images and determines whether the variations in the images are statistically significant. The algorithm has been developed and tested by application to 31P CSI data from the human forearm and brain. Our results demonstrate that MIMSTATS can detect signal at a very low signal-to-noise ratio in a reliable and reproducible fashion and provides a sound basis for testing hypotheses concerning differences in distribution of metabolites. PMID- 1593961 TI - Tuberculosis in apparently healthy milch cows. AB - Screening for mycobacteria was carried out on samples of normal milk, supramammary lymph nodes (SLNS) and udder tissue from apparently healthy milch cows, including the milk from those suspected of tuberculous mastitis. Milk samples from the slaughtered and live Fulani cows which were apparently healthy yielded 5% and 7% of tubercle bacilli, respectively, while suspected tuberculous milk from slaughtered cows and live cows yielded 8% and 10% of the bacilli, respectively. Tubercle bacilli were isolated both from SLNS with and without lesions. The udder tissue was positive for mycobacteria even though visible lesions were absent. PMID- 1593962 TI - Purification and properties of lactate dehydrogenase from Nocardia asteroides. AB - The lactate dehydrogenase (LDH) from Nocardia asteroides was purified to homogeneity by ammonium sulphate precipitation, gel filtration on Sephadex G-150 and DEAE-Sepharose column chromatography. The purified enzyme showed a single band in native condition which indicated its homogeneity. SDS-PAGE of the purified enzyme showed the presence of three bands which correspond to molecular weights of 60, 66 and 74 kDa. The pH and temperature optima of the purified enzyme were 9.5 and 50 degrees C, respectively. The metal ions Mn++, Fe++, Co++, Mg++ and Ca++, increased the purified LDH activity. On the other hand, enzyme activity was completely inhibited by CuCl2. Potassium chloride, ammonium sulphate and sodium chloride did not alter the enzyme activity. The purified enzyme exhibited a Km value of 1.6 x 10(-5) M for pyruvate. PMID- 1593963 TI - T-lymphocyte activity during prodromal and exanthem stages of measles infection. AB - The cell mediated immune response in the prodromal and exanthem clinical stages of measles infection was measured by the degree of T-lymphocyte activity (E rosette) and compared with controls. Data obtained showed T-cell activity which was markedly different in the stages of measles infection under investigation. PMID- 1593964 TI - Numerical taxonomy of Bacteroides and other genera of Gram-negative anaerobic rods. AB - A numerical taxonomy was performed on 157 cultures (141 different strains) of species of Bacteroides, Polyphyromonas, Prevotella [not Prevotella (Labroue, 1976)] and Fusobacterium. Isolates were each tested for 111 phenotypic characters which included possession of constitutive enzymes, fermentation of specific carbohydrates, gas chromatographic analysis of metabolic end-products and of cellular carboxylic acid composition. Computation of similarity coefficients was followed by a single-linkage cluster analysis. At the 94% similarity level, the following groupings at genus level were apparent: (1) Bacteroides ureolyticus; (2) Fusobacterium mortiferum, F. necrogenes, F. necrophorum, F. nucleatum and F. varium; (3) B. caccae, B. distasonis, B. eggerthii, B. fragilis, B. merdae, B. ovatus, B stercoris, B. thetaiotaomicron, B. uniformus and B. vulgatus; (4) B. splanchnicus; (5) Porphyromonas asaccharolytica; (6) B. bivius (Prevotella bivia); (7) B. disiens (P. disiens); (8) B. intermedius (P. intermedia);and (9) B. melaninogenicus (P. melaninogenica). Single isolates of B. ruminicola (P. ruminicola), B. denticola (P. denticola) and B. capillosus did not cluster with other strains. PMID- 1593965 TI - Human pulmonary nocardiosis. AB - The involvement of Nocardia species in human pulmonary infections was investigated. Pulmonary nocardiosis mimics pulmonary tuberculosis in both clinical symptoms and radiological characteristics. In third world countries where diagnosis is based solely on such findings, anti-tuberculosis regimens may indicate chronic tuberculosis when in fact pulmonary nocardiosis should have been treated. Differential diagnosis is recommended for efficient health care and cost effective drug use. PMID- 1593966 TI - Induction of beta-lactamase from Shigella flexneri UCSF-129: purification by affinity chromatography and some properties. AB - Lincomycin, an inhibitor of protein synthesis, was an excellent inductor of beta lactamase, and its total activity and specific activity were increased 2.5- and 3.6-fold respectively. The beta-lactamase produced by Shigella flexneri UCSF-129 was purified by affinity chromatography on phenylboronic acid-agarose with a type B column using an hydrophobic spacer arm (6-aminohexanoic acid activated with succinimide). The yield and specific activity were 96% and 29,283 U/mg, respectively. These were 1.7- and 3.8-fold higher, respectively, than those obtained by the traditional method using ion-exchange chromatography and gel filtration. The working-time was reduced to a third, and the enzyme preparation was shown to be pure by several criteria. From nine divalent cations assayed, only Sn(II) inhibited the enzyme by 74%, and the chloride ion did not have any effect on enzyme activity. PMID- 1593967 TI - Susceptibility to antimicrobial agents and plasmid carrying in Aeromonas hydrophila isolated from two estuarine systems. AB - Susceptibility to various antimicrobial agents and the presence of plasmids was investigated in eleven strains of Aeromonas hydrophila isolated from samples of sea water and these strains isolated from Aulacomya ater. Transference of resistance to Escherichia coli was attempted by conjugation and transformation experiments. The strains showed multiple resistance toward beta-lactam antibiotics and susceptibility to other antimicrobial agents. Five strains harboured plasmids with molecular weights below 5.7 MD. It was not possible to relate the resistance of the strains with the presence of their plasmids. PMID- 1593968 TI - Bacterial populations and the effect of phosphorus concentration in linear alkyl benzene sulphonate degradation by the OECD screening method. AB - The evolution of bacterial populations during biodegradation of linear alkyl benzene sulphonate by the OECD screening test was studied by direct microscopic counts, glucose metabolism and thymidine incorporation. Biodegradation dynamics were studied following the disappearance of surfactant and of surface tension. Important variations in bacterial density and activity at the initial stages of degradation were associated with the variability in biodegradation dynamics. PMID- 1593969 TI - An unusual yellow pigmented Pseudomonas species isolated from chlorinated municipal town water supply. AB - A Gram-negative non-fermentative rod (GN-NF) which produced a yellow non diffusible pigment is described. The isolate is typical of the heterotropic population of bacteria present in the chlorinated town water, as supplied to the city of Brisbane, Queensland, Australia. The strain could be not satisfactorily identified by Automatic Microbic Systems (Vitek) or API 20 NE protocols. Characterization tests, performed according to conventional methods, including other morphological and physiological characteristics, indicated a close relationship with the genus Pseudomonas. The phenotype was different from any previously described yellow and non-diffusible pigmented species in the genus Pseudomonas, including P. aureofaciens, P. palleronii, P. paucimobilis, and P. alcaligenes. The town water isolate showed a marked sensitivity to the vibriostatic agent 0/129 (2,4-diamino-6,7,diisopropyl-pteridine phosphate) at a concentration of 150 micrograms. PMID- 1593970 TI - Winning an arbitration: how evidence impacts the decision. PMID- 1593971 TI - AIDS education for registered nurses. PMID- 1593972 TI - Visiting nurse lobbies against risky behaviors. PMID- 1593973 TI - Pravastatin, simvastatin, and lovastatin for lowering serum cholesterol concentrations. PMID- 1593974 TI - Development of GABAergic modulation of mouse locomotor activity and pain sensitivity after prenatal benzodiazepine exposure. AB - Outbred CD-1 mice were exposed to oxazepam (15 mg/kg PO twice/day) on days 12-16 of fetal life, i.e., at a critical ontogenetic stage of Type II benzodiazepine (BDZ) receptor increase, and fostered at birth to untreated dams. Locomotor activity (single 30-min session in a Varimex apparatus), hot-plate responding, and muscimol (GABAa agonist) effects thereon [see normative data in (16)] were assessed on postnatal day 14, 21, or 28. Prenatal oxazepam did not affect the development of hot-plate responding and muscimol analgesia; however, it reduced activity on day 14 (as in previous studies) and modified the profile of muscimol effects at 21 days (time of first appearance of an adult-like pattern of activity) and at 28 days. Specifically, oxazepam mice showed a faster recovery from the initial depression after 1 mg/kg of muscimol at the former age and a lack of rebound hyperactivity at the latter age. These effects might be explained either 1) by an accelerated development of GABAergic regulatory mechanisms, or 2) by the same monoaminergic system changes which can account for other effects of prenatal BDZ exposure (1,3). In any event, the dissociation phenomena found in the present study strengthen the notion that GABAergic influences contribute to the modulation of locomotor activity and of pain reactivity by mechanisms which are at least in part separate from each other (16). PMID- 1593975 TI - Developmental neurotoxicity following premating maternal exposure to hexachlorobenzene in rats. AB - The maternal transfer of hexachlorobenzene (HCB) may place the developing organism at risk. The present study assessed the developmental neurotoxicity of HCB using a battery of behavioral tests. Two weeks prior to breeding, maternal rats were exposed via gavage to either 10 or 100 mg HCB/kg body weight. Behaviors evaluated in pups exposed maternally to HCB included the negative geotaxic reflex on postnatal day (PND) 6, 8, and 10, olfactory discrimination (PND 9-11), and the development of exploratory behavior (PND 15-20). Significant effects in these three tests indicated hyperactivity in HCB-exposed pups. No significant effects on learning (swim T-maze) or motor activity were detected in older offspring (PND 40 and 50 respectively). The acoustic startle response (ASR) revealed apparent age-related effects of maternal HCB exposure. On PND 23 pups from the high treatment group demonstrated significantly reduced ASR amplitude, whereas these same animals, tested on PND 90 (using a reflex modification design), showed elevated ASR amplitude relative to the controls. This work demonstrates that HCB is a behavioral teratogen, and suggests that human fetuses and suckling infants may be at risk from the neurotoxic effects of HCB. PMID- 1593976 TI - Effects of cocaine and alcohol use in pregnancy on neonatal growth and neurobehavioral status. AB - Effects on fetal growth and neonatal behavior of cocaine and alcohol use in pregnancy were investigated in infants born to women in a low-income, predominantly black population. Despite the increased use of cocaine by pregnant women and the accompanying public concern, behavioral studies of exposed neonates are limited in number and scope. In most studies, confounding factors (e.g., polydrug abuse, prematurity, infant health status) have not been controlled so the actual effects of cocaine and other drug exposure are not clear. Accordingly, this study investigated effects of prenatal drug exposure although controlling experimentally for other factors known to be associated with poor outcomes in infants: prematurity, other illicit drug use, associated diseases (e.g., sexually transmitted diseases [STDs]), and duration of drug use. In addition, other factors statistically controlled were: experimenter effects, timing of assessment, and effects of duration, amount, and frequency of cocaine, alcohol, marijuana, and nicotine exposure. One hundred and seven full-term infants were assessed at 2, 14, and 28 days using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) by testers blind to infant status. Growth factors (i.e., birthweight, length, head circumference) were also assessed. PMID- 1593977 TI - Branched chain amino acids improve radial-arm maze acquisition and water maze forced-choice learning in rat offspring exposed in utero to hyperphenylalaninemia. AB - Maternal phenylketonuria results in a high incidence of children born mentally retarded. We showed that the large neutral amino acids valine, isoleucine, and leucine (VIL) ameliorate the effects of intrauterine hyperphenylalaninemia in rats on a test of complex maze learning. To further test the ameliorative effects of VIL on intrauterine CNS development during hyperphenylalaninemia, gravid rats were administered a phenylalanine/p-chlorophenylalanine (index group) supplemented diet with or without VIL added. Controls were given standard diet with or without VIL. All groups were pair-fed to the index group. As adults, the progeny exposed in utero to hyperphenylalaninemia showed characteristic learning impairments in a complex water (Cincinnati) maze on forced and elective-choice phases of the task and deficits in radial-arm maze and Morris maze acquisition, whereas those exposed to hyperphenylalaninemia combined with VIL showed no deficits in the forced-choice phase of Cincinnati maze learning and no evidence of radial-arm maze deficits. However, the improvement was not complete, with no ameliorative effects obtained on the elective-choice phase of the Cincinnati maze or on the Morris hidden platform test. No deficits were seen on phases containing test trials for memory function (Olton and Morris mazes). The acquisition differences occurred in the absence of any effects of VIL on maternal weight gain during gestation, maternal serum amino acid concentrations of phenylalanine or tyrosine, or effects on offspring growth. VIL alone produced no adverse or enhancing effects on learning or memory. Based on these data it was concluded that the VIL supplement continues to show promise as a potential treatment for intrauterinely acquired mental deficiency associated with maternal phenylketonuria. PMID- 1593978 TI - A method for measuring locomotor behavior in rodents: contrast-sensitive computer controlled video tracking activity assessment in rats. AB - A newer locomotor activity system for rodents is described. The system consists of a black, ventilated test chamber, internally lighted with a ceiling mounted video camera. The camera's image is transmitted to a contrast-sensitive tracker which maps the point of highest contrast and relays the digitalized coordinates to a PC. Dedicated software stores the information and simultaneously displays a map of the tracked subject. To illustrate the system's utility, results from an experiment are presented using an established behavioral teratogen, phenytoin. Pregnant Sprague-Dawley CD rats were exposed to 0 or 200 mg/kg of phenytoin by gavage on embryonic days 7-18 and the offspring tested in the videotracker activity monitoring device. Phenytoin is known to induce hyperactivity and circling behavior in the offspring. The system revealed that phenytoin-exposed offspring that exhibit neurological impairment were hyperactive compared to controls and the effect was predominantly seen in females. These animals exhibited more section transitions and more central and peripheral activity. When peripheral activity was subdivided into that occurring along corners versus sides, it was found that corner activity represented only a small component of the group differences whereas the side component represented most of the effect. Moreover, phenytoin offspring exhibiting the circling defect were found to display a qualitatively different pattern than noncirclers or controls. Videotracking represents a different approach to the analysis of locomotor activity patterns in experimental animals compared to older methods. Two advantages of this method are higher spatial resolution and not having to pre specify data capture intervals. Other features are detailed regional movement information and qualitative mapping of ambulatory patterns. PMID- 1593979 TI - Lead exposure and the central auditory processing abilities and cognitive development of urban children: the Cincinnati Lead Study cohort at age 5 years. AB - This analysis examined the relationship between lead exposure as registered in whole blood (PbB) and the central auditory processing abilities and cognitive developmental status of the Cincinnati cohort (N = 259) at age 5 years. Although the effects were small, higher prenatal, neonatal, and postnatal PbB levels were associated with poorer central auditory processing abilities on the Filtered Word Subtest of the SCAN (a screening test for auditory processing disorders). Higher postnatal PbB levels were associated with poorer performance on all cognitive developmental subscales of the Kaufman Assessment Battery for Children (K-ABC). However, following adjustment for measures of the home environment and maternal intelligence, few statistically or near statistically significant associations remained. Our findings are discussed in the context of the related issues of confounding and the detection of weak associations in high risk populations. PMID- 1593980 TI - Prenatal exposure to cocaine disrupts cocaine-induced conditioned place preference in rats. AB - Cocaine-induced conditioned place preference (CPP) was tested in adult offspring of Sprague-Dawley dams that had been injected subcutaneously with 40 mg/kg/3cc cocaine HCl (C40) daily from gestational days 8-20, pair-fed (PF) dams injected with saline, and nontreated control (LC) dams. C40 and PF dams gained significantly less weight than LC dams, although offspring body weights did not differ among the three prenatal treatment groups at birth or in adulthood. Significant place conditioning was obtained in LC and PF offspring when either 2.0 or 5.0 mg/kg of cocaine was paired with the designated place. In contrast, C40 offspring did not exhibit place conditioning at either training dose. Yet, all animals exposed to 5 mg/kg of cocaine during conditioning exhibited less activity during the test (when no cocaine was given) than controls given unpaired exposures to the apparatus and cocaine and C40 offspring did not differ from LC and PF offspring in this respect. Therefore, despite their lack of a conditioned place preference for cocaine, rats that had been exposed gestationally to cocaine nevertheless revealed an effect of cocaine during conditioning in one aspect of their test behavior. Possible explanations for the lack of cocaine-induced place preference in these animals include a learning deficit or a change in cocaine's effectiveness as a reward. PMID- 1593981 TI - Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat. AB - Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence. PMID- 1593982 TI - The ontogeny of behavioral sensitization to phencyclidine. AB - Repeated exposure of adult rats to a variety of psychoactive compounds can result in altered behavioral responsiveness to later exposures depending on the dose, route, and frequency of administration and time of testing. The ontogeny and mechanism of this altered responsiveness are not well understood. To determine when behavioral sensitization to phencyclidine (PCP) occurs, neonatal and early developmental exposure effects of PCP were assessed on later behavioral responsiveness to a PCP challenge. Rat pups were injected daily for nine days beginning on either postnatal days (PNDs) 1 or 22 with 0.9% saline, 5.0 or 10.0 mg/kg PCP-HC1 (s.c.). Ten days following the last injection, rats were given one of the following drug challenges: 0.9% saline, 5.0 or 10.0 mg/kg PCP-HC1 (s.c.). Locomotor activity, ataxia, and several other behaviors were measured for 1 h beginning 2-3 min after the challenge injection. Two major findings emerged from these studies. First, pups treated subchronically with PCP on PNDs 1-9 did not exhibit any difference in behavioral sensitivity to a PCP challenge when tested on PND 19 compared to subchronically treated saline controls. In contrast, pups subchronically treated with PCP on PNDs 22-30 exhibited an increased sensitivity to the behavioral effects of a PCP challenge. These data suggest that PCP has age dependent exposure effects that occur sometime after the first postnatal week and that result in an enhanced behavioral responsiveness to PCP later in life. PMID- 1593983 TI - Effects of arecoline and scopolamine on open field behavior of adult monkeys treated with lead during the first year postpartum. AB - Nursery-reared rhesus monkeys were treated with no or moderate levels of lead during the first year postpartum. Previously, the lead-treated monkeys exhibited behaviors in the nonhuman primate version of the open field (10) resembling those caused by hippocampal lesions. The current study investigated the mechanism(s) underlying these lead-related effects using a cholinergic agonist (arecoline) and antagonist (scopolamine) as pharmacological probes that were administered prior to open field testing at 5 and 6 years of age, respectively. Arecoline decreased locomotion and number of sectors entered. Scopolamine decreased defecation frequency. Neither drug interacted with prior lead treatment, indicating limited cholinergic involvement in the expression of these alterations. The lead-treated subjects continued to exhibit alterations as previously reported (10); specifically, a longer latency to enter the open field, increased frequency and duration of environmental exploration and, at 5 years of age, decreased duration of inactivity in the open field. These effects were seen four and five years after lead treatment ended and nearly three and four years after blood lead levels had declined to less than or equal to 5 micrograms/dL. Although latency to enter and duration of inactivity seem to be approaching control levels, the increased exploration does not. PMID- 1593984 TI - Reliability of selected tests from the neurobehavioral evaluation system. AB - NES is a widely used battery of tests designed for use in occupational health studies. Despite its widespread use, information on the reliability of the tests is limited. This article reviews the importance of test reliability and presents the results of analyses which were undertaken to examine the reliability of 11 tests and a mood rating scale contained in the NES. The NES tests were administered to 66 subjects on two testing days separated by a minimum of seven days. Seven tests were administered twice on each test day with a 3-hour interval between testing, and four of the tests were presented only once each test day. Test reliabilities were estimated for various summary measures for each test. Suggestions are made on the appropriate selection of tests and use of these. PMID- 1593985 TI - Effects of prenatal diphenylhydantoin treatment on reproductive outcome, development, and behavior in rats. AB - Pregnant Sprague-Dawley rats were administered sodium diphenylhydantoin (DPH) by gavage on gestation days 9-18 in doses of 0, 100, or 200 mg/kg. DPH-treated dams showed a dose-related decrease in weight gain throughout the drug treatment period. Offspring had significantly lowered birth weights, along with increased mortality through the first 30 days of life. In one of the experiments specifically designed to measure pup mortality, the rates were 41.4% and 60.7% respectively, for the 100 and 200 mg/kg DPH groups. Shortly after eye opening, many of the DPH-treated animals developed chromodacryorrhea, a condition that remained throughout the experiment. Aside from lowered body weights, no differences were observed in the attainment of several standard developmental landmarks. During the neonatal period, the pups exposed in utero to 100 mg/kg DPH showed a significant increase in pivoting locomotion on postnatal days 7 and 9. As adults, the animals exposed to 200 mg/kg DPH showed significant increases in locomotor activity measures. Both DPH groups developed a dose-related and highly abnormal spontaneous circling behavior. These results confirm a small but growing body of literature that demonstrates that DPH is a behavioral teratogen. PMID- 1593986 TI - Behavioral sequelae in young rats of acute intermittent antenatal hypoxia. AB - Several studies have examined behavioral sequelae of acute or chronic pre- or postnatal hypoxia. However, few of these tested a large battery of behavioral functions, particularly those following relatively mild, intermittent hypoxia. Also, in few studies were the hypoxic pups cross-fostered or the experimenter blinded as to experimental group. In addition, in almost no studies were concomitant hypoxic-induced brain biochemicals measured. The present study tested the hypotheses that mild, intermittent antenatal hypoxia can lead to long-term alterations in neurobehavioral development, as well as neurochemical changes. PMID- 1593987 TI - Use of the lesion model for examining toxicant effects on cognitive behavior. AB - It is often beneficial to use a model to help understand unknown effects and relate those effects to an existing body of knowledge. In much of the early development of behavioral toxicology, the pharmacological model has served as a valuable theoretical guide, especially with regard to dosing and kinetic parameters. However, as with any model, it has certain limitations. The lesion model has complementary features which provide valuable insights into the behavioral effects of toxicants. This is particularly true for effects which persist long after the end of toxicant exposure. There is much literature describing effects of brain lesions on behavior. By comparing results from toxicology studies to those of lesion studies, one can take advantage of this trove of information to gain a better insight into the possible loci of toxic effects, and to identify tests which would be useful in further describing the nature of the toxic effects. In this article, we examine the theoretical and practical utility of the lesion model. Examples are given showing how it has proven useful in interpreting the cognitive effects of exposure of monkeys to lead and polychlorinated biphenyls (PCBs). These exposures produced syndromes that closely resemble the effects of lesions in the frontal cortex or limbic system. PMID- 1593988 TI - Proconvulsant activity of endosulfan in amygdala kindling. AB - The proconvulsant properties of the chlorinated hydrocarbon insecticide, endosulfan, were investigated using electrical kindling of the amygdala. Male rats were implanted with electrodes in the amygdala and stimulated once daily with a standard kindling stimulus 60-90 min following endosulfan (0, 2.5, 5.0 mg/kg, PO). No alterations were observed in either the threshold to induce an afterdischarge (AD) or the duration of clonus upon seizure generalization. Endosulfan significantly reduced the number of stimulations required to produce Stage 5 generalized seizures. Seizures prior to stimulation were evident in a subset of animals from both dosage groups and were never observed in controls. The presence of kindled seizures was maintained in the absence of further dosing, as amygdala stimulation 2-4 weeks after the last endosulfan treatment resulted in generalized seizures in all animals. These results suggest that faster kindling rates induced by endosulfan are not readily attributable to transient toxicant related increases in excitability of the nervous system. It was concluded that endosulfan has proconvulsant properties that may be related to an action on GABA within the central nervous system. PMID- 1593989 TI - A characterization of chemical kindling with the pesticide endosulfan. AB - In a companion article (see this issue), the proconvulsant properties of the pesticide endosulfan in electrical kindling of the amygdala are described. In the present report, an evaluation of the chemical kindling properties of endosulfan is presented. Repeated administration (3 times per week for a total of 21 doses) of endosulfan (5 and 10 mg/kg in corn oil, PO) was found to induce behavioral seizures in rats. Behavioral seizure development was most apparent in the high dose group (10 mg/kg). Heightened seizure responsiveness to a challenge dose was maintained following a two-week, drug-free period, arguing against cumulative toxicity as a mechanism for seizure induction. Electrical kindling induced by once daily stimulation of the amygdala began approximately 4 weeks after the final dose of endosulfan. In the absence of further dosing, a significant facilitation in the rate of kindling development was evident as a function of prior treatment with endosulfan. An enhancement in the rate of kindling was also evident in the low dose group (5 mg/kg) in the absence of clonic seizure development during dosing. A history of endosulfan treatment failed to affect threshold for inducing an afterdischarge (AD) and had equivocal effects on the development of AD with repeated stimulation. Pretreatment with a single high dose of endosulfan 2 weeks prior to electrical kindling was without effect on the development of the kindled response. Endosulfan has been reported to decrease binding of gamma-amino-butyric acid (GABA). Chemical kindling with endosulfan may result from the interaction of this pesticide with GABA-mediated neurotransmission in the central nervous system (CNS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1593990 TI - Motor assessment of cocaine/polydrug exposed infants at age 4 months. AB - Fifty nondrug-exposed infants and 74 cocaine/polydrug-exposed infants were evaluated on the Movement Assessment of Infants (MAI). The test provides an assessment of risk for motor dysfunction at age 4 months. There was a significant difference in total risk scores between the two groups of infants with cocaine exposed infants having higher total risk scores (p less than .0001). Categorical risk scores revealed significant differences between the infants in muscle tone, primitive reflexes, and volitional movement with cocaine-exposed infants scoring more poorly in each category (p less than .0001). The groups scored differently on 11 of the 49 MAI items in those categories. Placement of infants within previously established ranges of risk scores (0-7 = no risk; 8-13 questionable risk; greater than 13 = high risk) revealed a significant difference in distribution between the two groups (p less than .0001). Earlier studies of the effects of intrauterine drug exposure have not revealed significant differences in motor development. The MAI demonstrated differential assessments of risk for motor dysfunction between cocaine-exposed and nondrug-exposed infants. PMID- 1593991 TI - Examining the past, present, and future of clinical genetics. PMID- 1593992 TI - Hennepin county's drop your guns campaign. Sound strategy or merely popular policy? PMID- 1593993 TI - Is the new genetics outpacing primary medicine? PMID- 1593994 TI - The CLIA '88 final rule. A guide to compliance. PMID- 1593995 TI - The revolution in clinical genetics. Practical applications. AB - Recent advances in genetics directly affect family physicians. Many diagnostic tests are currently available to screen the fetus for malformations and genetic diseases, and gene therapy is slowly becoming a reality. This article discusses some of the screening techniques available, including chromosome analysis, ultrasound, and DNA studies. PMID- 1593996 TI - Health care antitrust woes. Does the state legislature hold the solution? PMID- 1593997 TI - Sexual harassment in the workplace. How to recognize, investigate, and prevent the problem. PMID- 1593998 TI - Where HealthRight went wrong. PMID- 1593999 TI - HealthRight has the wrong stuff. PMID- 1594001 TI - What is a responsible physician? PMID- 1594000 TI - HIV-infected health worker sues care facility. PMID- 1594002 TI - Breast conservation therapy. The St. Luke's Hospital experience. AB - Between 1979 and 1987, 170 patient with stages 0, I and II breast cancer were treated with breast conservation therapy. Twenty-eight women (16%) had intraductal carcinomas, 110 (65%) stage I disease and 32 (19%) had stage II breast cancers. Seventy-five percent of the patients received no adjuvant systemic treatment, whereas 20% received adjuvant chemotherapy and 5% were given Tamoxifen. All patients received radiation therapy to the breast after lumpectomy and, when appropriate, axillary dissection. Twelve patients (7%) recurred within the treated breast, whereas two patients (1%) recurred in regional lymph nodes. Fourteen women (8%) developed distant metastases and seven women (4%) developed contralateral breast cancer. The actuarial 5 year disease-free survival was 92% for the patients with intraductal carcinoma, 90% for T1 and 65% for T2 patients. Overall actuarial survival was 100%, 96% and 87%, respectively. The St. Luke's Hospital results are comparable to those reported in the literature. We conclude that breast conservation therapy, including irradiation, is an alternative to modified radical mastectomy and that this option should be thoroughly discussed with the patient. PMID- 1594003 TI - The neurological aspects of acquired immune deficiency syndrome (AIDS)--a clinical review. AB - Ten years after it was diagnosed, AIDS is estimated to have affected 10 million people worldwide and about 2-3 million people in the United States. Initially considered to be a disease of coasts (New York, California, Florida), AIDS is making inroad to mid-America as well. It involves the nervous system in a variety of ways. These include direct involvement by the virus, secondary opportunistic infections, and tumors. The spectrum of nervous system involvement is the subject of our review. PMID- 1594004 TI - "... More on this story, and tape at 10". PMID- 1594005 TI - Analysis of the PRO. PMID- 1594006 TI - 1992 CPT hospital codes. PMID- 1594007 TI - Clinic will 'link' the indigent patient into the existing health care system. Interview by Dennis Weiser. PMID- 1594008 TI - Legal challenges to denials of insurance coverage for "experimental" medical treatments. PMID- 1594009 TI - Liability epidemic--health care costs: break the linkage. PMID- 1594010 TI - Diagnosis and management of ulnar nerve entrapment. AB - Ulnar nerve entrapment can be divided into compression at the elbow and the wrist. Etiologies range from direct trauma to metabolic derangements. Guidelines for diagnosis at each site have been presented. Surgical release at the elbow begin at the mid arm where the nerve passes from the anterior to the posterior compartment through the intermuscular septum and extends into the proximal forearm, where it dives down under the heads of the flexor carpi ulnaris. Surgical release at the wrist involves deroofing the canal of Guyon. The authors' preferred methods of release at each site are given along with a description of positive care. PMID- 1594011 TI - Trends in prostate cancer--United States, 1980-1988. AB - Among men, carcinoma of the prostate is the second most common cancer and the second most common cause of death from cancer in the United States (1). During 1992, an estimated 132,000 men will be diagnosed with and 34,000 will die from prostate cancer (2). This report describes trends in prostate cancer incidence and mortality by patients' age, race, and state of residence from 1980 through 1988. PMID- 1594012 TI - Breast and cervical cancer surveillance, United States, 1973-1987. AB - Breast and cervical cancer incidence and mortality rates were reviewed for the period 1973-1987. For breast cancer, mortality has been relatively stable, increasing from 26.9/100,000 women in 1973 to 27.1 in 1987. Alternatively, data from the National Cancer Institute's Surveillance, Epidemiology, End Results Program (SEER) showed a 36% increase in the incidence of this malignancy over the same period. In 1987, overall incidence of invasive breast cancer was 111.9/100,000 women. White women experienced lower overall mortality rates and higher overall incidence than black women; however, these differences varied by age. Examination of breast cancer incidence by stage of disease at diagnosis revealed that rates for distant and regional disease have remained relatively stable since 1973. In contrast, rates of localized and in situ cancers exhibited an increase in the 1980s that may correspond to increased use of mammography in this country. The rate of decline in cervical cancer incidence and mortality has slowed in recent years. In 1987, 3.0 cervical cancer deaths/100,000 women occurred. SEER incidence for invasive disease for that year was 8.2/100,000. Rates varied by race, age, state, and stage of disease. In general, black women experienced much higher incidence and mortality from invasive cervical cancer than white women. For both races, rates of in situ disease were highest among young women and decreased rapidly with age. Rates of in situ cervical cancer were consistently higher than rates of invasive cancer for the time period studied. PMID- 1594013 TI - Cancer screening behaviors among U.S. women: breast cancer, 1987-1989, and cervical cancer, 1988-1989. AB - Data from the Behavioral Risk Factor Surveillance System (BRFSS) were used to examine trends in breast and cervical cancer screening behaviors among U.S. women in selected states. Data reported are from the 1987, 1988, and 1989 BRFSS for breast cancer screening (mammography) and from the 1988 and 1989 BRFSS for cervical cancer screening (Papanicolaou [Pap] smear). Results are presented as either state-specific or state-aggregate data for the years noted above. State specific analyses indicated that self-reported mammography utilization increased between 1987 and 1989. Although whites and blacks reported similar mammography utilization rates both for screening and for a current or previous breast problem, disparities were evident among women of different ages and incomes. The proportion of women who reported ever having had a Pap smear and having heard of a Pap smear were extremely high and remained fairly consistent across the 2 survey years. State-aggregate analyses, however, showed that the percentage of women who had had a Pap smear within the previous year was negatively associated with age and positively associated with income. A higher proportion of blacks than whites obtained Pap smears. These results indicate that certain segments of the population are not taking full advantage of available breast and cervical cancer screening technologies. Public health strategies, such as those outlined in the Breast and Cervical Cancer Mortality Prevention Act of 1990 (Public Law 101-354), should enhance screening opportunities for these women. PMID- 1594014 TI - Renal transplantation in children. A report of the North American Pediatric Renal Transplant Cooperative Study. AB - BACKGROUND: Previous studies of renal transplantation in children have focused on the survival of grafts and patients. Little information is available about the cause of renal disease, the sources of donated organs, or children's growth after transplantation. The North American Pediatric Renal Transplant Cooperative Study was organized to identify the diseases that require transplantation and to analyze factors that affect the success of transplantation in children. METHODS: We collected data from 73 pediatric transplantation centers from 1987 through 1990. These data included information about demographic characteristics of patients, graft function, and therapy one month after transplantation and every six months thereafter for each patient 17 years of age or younger. RESULTS: Altogether, 1550 children received 1667 renal allografts during this period; 31 percent of the children were five years of age or younger. Forty-three percent of the transplanted kidneys came from a living related donor, and 57 percent from a cadaver. The two most common causes of renal disease leading to transplantation were congenital malformations of the kidneys and urinary tract (42 percent of the patients) and focal segmental glomerulosclerosis (12 percent). One year after transplantation, the rate of graft survival in recipients of a kidney from a living related donor was 89 percent; it was 80 percent after three years. For recipients of cadaver kidneys, the comparable rates were 74 percent and 62 percent, respectively (P less than 0.001). The best growth was observed in patients who were no more than five years old at the time of transplantation. During follow-up, 79 patients died, and cancer developed in 12 patients. CONCLUSIONS: The most common causes of end-stage renal disease in children and adolescents are congenital malformations of the kidneys and urinary tract and focal segmental glomerulosclerosis. The rates of graft survival at one and three years are better in children and adolescents who receive a kidney from a living related donor than in those who receive a kidney from a cadaver. PMID- 1594015 TI - The use of digoxin-specific Fab fragments for severe digitalis intoxication in children. AB - BACKGROUND: Because life-threatening digitalis intoxication is unusual in children, treatment with digoxin-specific-antibody Fab fragments (Fab) has rarely been reported. We describe the efficacy of Fab in the treatment of children with severe digitalis intoxication. METHODS: Twenty-nine children with intoxication due to digoxin (28) or digitoxin (1) received Fab at 21 participating hospitals between 1974 and 1986. Data were gathered about the patients' medical illnesses, doses and serum concentrations of digitalis, responses to Fab therapy, and outcomes. RESULTS: In the infants and young children with acute digoxin intoxication, the digoxin doses ranged from 0.30 to 0.96 mg per kilogram of body weight; two adolescents had severe intoxication after doses of only 0.20 and 0.26 mg per kilogram. The serum digoxin concentrations ranged from 3.0 to greater than 100 ng per milliliter (mean, 13.8). Atrioventricular block (present in 22 patients [76 percent]) was the most common sign of toxicity. All the patients in this series had severe disturbances of cardiac rhythm, hyperkalemia (mean serum potassium concentration, 5.4 mmol per liter), or both. In 27 patients (93 percent), digitalis toxicity resolved after the administration of Fab. Of the 19 patients for whom data were available on the timing of the response to Fab, 15 responded within 180 minutes. Three patients required retreatment with Fab. Seven died of complications unrelated to the administration of Fab. CONCLUSIONS: We recommend that Fab be used in the treatment of digitalis poisoning in infants and young children who have ingested greater than or equal to 0.3 mg of digoxin per kilogram, who have underlying heart disease, or who have a serum digoxin concentration of greater than or equal to 6.4 nmol per liter (greater than or equal to 5.0 ng per milliliter) in the elimination phase; and who also have a life-threatening arrhythmia, hemodynamic instability, hyperkalemia, or rapidly progressive toxicity. Adolescents, who are more sensitive to the toxic effects of digoxin than younger children, may require treatment with Fab after ingesting lower doses. PMID- 1594016 TI - Risk of leukemia after chemotherapy and radiation treatment for breast cancer. AB - BACKGROUND: Few studies have evaluated the late effects of adjuvant chemotherapy for breast cancer. Moreover, the relation between the risk of leukemia and the amount of drug given and the interaction of chemotherapy with radiotherapy have not been described in detail. METHODS: We conducted a case-control study in a cohort of 82,700 women given a diagnosis of breast cancer from 1973 to 1985 in five areas of the United States. Detailed information about therapy was obtained for 90 patients with leukemia and 264 matched controls. The dose of radiation to the active marrow was estimated from individual radiotherapy records (mean dose, 7.5 Gy). RESULTS: The risk of acute nonlymphocytic leukemia was significantly increased after regional radiotherapy alone (relative risk, 2.4), alkylating agents alone (relative risk, 10.0), and combined radiation and drug therapy (relative risk, 17.4). Dose-dependent risks were observed after radiotherapy and treatment with melphalan and cyclophosphamide. Melphalan was 10 times more leukemogenic than cyclophosphamide (relative risk, 31.4 vs. 3.1). There was little increase in the risk associated with total cyclophosphamide doses of less than 20,000 mg. CONCLUSIONS: Although leukemia occurs in few patients with breast cancer, significantly elevated risks were linked to treatments with regional radiation and alkylating agents. Melphalan is a more potent leukemogen than cyclophosphamide or radiotherapy. Low risks were associated with the levels of cyclophosphamide in common use today. Systemic drug therapy combined with radiotherapy that delivers high doses to the marrow appears to enhance the risk of leukemia. PMID- 1594017 TI - Brief report: intragenic deletion of the KALIG-1 gene in Kallmann's syndrome. PMID- 1594018 TI - Prognostic factors and treatment decisions in axillary-node-negative breast cancer. PMID- 1594019 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 26-1992. A 38-year-old obese man with hypertension, diabetes mellitus, and slowly progressive right hemiparesis. PMID- 1594020 TI - Breast cancer therapy--the price of success. PMID- 1594021 TI - Kallmann's syndrome--beyond "migration". PMID- 1594023 TI - Where have all the primary care applicants gone? PMID- 1594022 TI - Where have all the primary care applicants gone? PMID- 1594024 TI - Where have all the primary care applicants gone? PMID- 1594025 TI - Where have all the primary care applicants gone? PMID- 1594026 TI - Where have all the primary care applicants gone? PMID- 1594027 TI - Where have all the primary care applicants gone? PMID- 1594028 TI - Clinical problem-solving: the many pitfalls in the diagnosis of myeloma. PMID- 1594029 TI - Clinical problem-solving: the many pitfalls in the diagnosis of myeloma. PMID- 1594030 TI - Clinical problem-solving: the many pitfalls in the diagnosis of myeloma. PMID- 1594031 TI - Clinical problem-solving: the many pitfalls in the diagnosis of myeloma. PMID- 1594032 TI - Required vision testing for older drivers. PMID- 1594033 TI - The patient as historian. PMID- 1594034 TI - The decade of the brain. PMID- 1594035 TI - Genetically engineered foods get green light. PMID- 1594036 TI - Ethical problems in the genes. PMID- 1594037 TI - What frontiers for Frontier? AB - The Human Frontier Science Program is a bold attempt to support the next century's biology research. Its horizons should not be limited. PMID- 1594038 TI - Plant biology. Twenty-first century crops. PMID- 1594039 TI - Physiology. The work that muscles can do. PMID- 1594040 TI - Human evolution. Diabetes running wild. PMID- 1594041 TI - Gene regulation. Transcriptional transgressions. PMID- 1594042 TI - Alpha-particles and leukaemia. PMID- 1594043 TI - Alpha-particles and leukaemia. PMID- 1594044 TI - New Middle Pleistocene hominid crania from Yunxian in China. AB - Two fossil human crania have been found in Middle Pleistocene terrace deposits of the Han River in Yun county (Yunxian), Hubei province, China (Figs 1 and 2). These damaged but relatively complete adult specimens show a mixture of features associated both with Homo erectus and with 'archaic H. sapiens'. The Yunxian crania (Figs 3 and 4), although crushed and distorted to varying degrees, are unusual in having major elements of the basicranium, palate, face and cranial vault preserved together. The specimens reveal many details of facial and basicranial anatomy rarely seen in hominid crania of comparable antiquity. Moreover, they are the most complete crania of such great age discovered on the Asian mainland. They consequently throw new light on Middle Pleistocene hominid diversity and the relationships among regionally disparate Middle Pleistocene hominids. PMID- 1594045 TI - Animal model of Gaucher's disease from targeted disruption of the mouse glucocerebrosidase gene. AB - Gaucher's disease is the most prevalent lysosomal storage disorder in humans and results from an autosomally inherited deficiency of the enzyme glucocerebrosidase (beta-D-glucosyl-N-acylsphingosine glucohydrolase), which is responsible for degrading the sphingolipid glucocerebroside. An animal model for Gaucher's disease would be important for investigating its phenotypic diversity and pathogenesis and for evaluating therapeutic approaches. A naturally occurring canine model has been reported but not propagated. Attempts to mimic the disease in animals by inhibiting glucocerebrosidase have been inadequate. Here we generate an animal model for Gaucher's disease by creating a null allele in embryonic stem cells through gene targeting and using these genetically modified cells to establish a mouse strain carrying the mutation. Mice homozygous for this mutation have less than 4% of normal glucocerebrosidase activity, die within twenty-four hours of birth and store glucocerebroside in lysosomes of cells of the reticuloendothelial system. PMID- 1594046 TI - Mechanical performance of scallop adductor muscle during swimming. AB - Mechanical performance of skeletal muscle has long been the subject of intense interest, but the details of in vivo performance of individual skeletal muscles during normal locomotion remain largely unknown. Performance in vitro has been described with considerable precision under simplified loading conditions. The force production and shortening velocity of most muscles, however, probably change continuously during natural movements. Therefore, modelling in vivo performance on the basis of in vitro contractile properties is subject to large degrees of uncertainty. Designing in vitro experiments that effectively examine the limits of mechanical performance requires increasing knowledge of precisely how muscles are used during normal movements. We report here measurements of the mechanical performance of the adductor muscle in scallops during jet-propulsion swimming. Swimming in scallops is powered solely by the striated portion of the single adductor muscle. Exploiting this simple locomotor morphology with simultaneous high-resolution measurements of pressure and flow rate, we have recorded nearly instantaneous measurements of the performance of a single skeletal muscle during normal locomotion. PMID- 1594047 TI - More on HIV testing. PMID- 1594048 TI - More on HIV testing. PMID- 1594049 TI - More on third-party payers. PMID- 1594050 TI - Multidimensional learning. PMID- 1594051 TI - Doctors' diplomacy. PMID- 1594052 TI - Not so good to the last drop. Ethylene glycol poisoning in a coffee-consuming camper. PMID- 1594053 TI - Snakebite in the tarheel state. Guidelines for first aid, stabilization, and evacuation. AB - Snakebite is relatively common in North Carolina. The Copperhead is the most common offender, though we have representatives of all three genera of the Pit Viper family in addition to the Coral Snake. Pit Vipers are identified by the characteristic triangular head, elliptical eyes, well-developed fangs, and with the Rattlesnakes, a tail rattle. The Coral Snake is identified by its characteristic color pattern with red bands adjacent to yellow bands. Treatment is initiated by the safe identification of the snake, taking care to avoid a second bite. A lymphatic constriction band is applied above the bite and an Extractor, if available, is applied within three minutes. The extremity is splinted and the victim evacuated to the nearest trauma center as soon as possible. PMID- 1594055 TI - Epilepsy. PMID- 1594054 TI - The prevention of childhood lead poisoning in North Carolina. PMID- 1594056 TI - Changing nutritional concerns in North Carolina. The state of our health. PMID- 1594057 TI - Notes from abroad. Former North Carolina physician recalls his New York and North Carolina experiences. PMID- 1594058 TI - Hair artifacts that may simulate disease. PMID- 1594059 TI - Helicopters and Aunt Minnie. PMID- 1594060 TI - Passion and compassion. The healing arts. PMID- 1594061 TI - The genetic screening of multifactorial disorders. PMID- 1594062 TI - [Postpartum thyroid disorders; a difficult recovery following childbirth]. PMID- 1594063 TI - [Insulinoma and octreotide]. PMID- 1594064 TI - [Surgical treatment of insulinoma: the importance of intra-operative echography]. PMID- 1594065 TI - [Chromosome aberrations in non-Hodgkin lymphoma and in Hodgkin's disease]. PMID- 1594066 TI - [Incidence of postpartum thyroid function disorders in The Netherlands]. AB - In a longitudinal study the incidence of postpartum thyroid dysfunction in the Netherlands was investigated in an unselected open population. There were 293 women who were screened by repeated assessments of thyroid function until 34 weeks postpartum at 6-week intervals. Thyroid dysfunction was defined as abnormal TSH values accompanied by abnormal FT4 and (or) FT3 values. The frequency of postpartum thyroid dysfunction was 7.2% (n = 21). Most of the thyroid dysfunction occurred between 16 and 28 weeks postpartum. There were five women with subclinical thyroid dysfunction: abnormal TSH values with complementary FT4 and (or) FT3 changes within normal limits. Four of them showed (marked) increase in antimicrosomal antibody titres. With the inclusion of the five women the frequency rose to 8.9%. These data appear representative for the Netherlands as a whole, suggesting that every year 14,000 women suffer from (transient) postpartum thyroid dysfunction. PMID- 1594067 TI - [Cancer incidence in the mid- and south region of Limburg in 1986-1988]. AB - To estimate the cancer incidence in the middle and southern part of the province of Limburg and to compare these rates with results of the Eindhoven Cancer Registry (IKZ/SOOZ), we carried out a descriptive investigation in the regional cancer registry Comprehensive Cancer Centre Limburg (IKL). The IKL has started a cancer registry in the province of Limburg in the framework of the national cancer registry. Since 1986 all hospitals and pathological laboratories in the area make their data available to the IKL cancer registry. Age-standardized incidence rates were calculated using the European Standard Population. The incidence rate for all malignancies combined over 1986-1988 was 406.3 per 100,000 per year in males and 273.0 per 100,000 per year in females. These incidence rates are very similar to the rates calculated by the Eindhoven Cancer Registry for the years 1983-86. However, the incidence rates are lower in the IKL area for malignancies of the stomach (males, females), bladder (males, females) and ovary. The incidence rates are higher for malignancies of the lung (females), pleura (males) and for 'primary tumor unknown' (males). The incidence rates of the IKL cancer registry correspond very closely to the rates of the Eindhoven cancer registry. However, differences in published mortality rates of both regions compared with the remaining part of the Netherlands suggest that the incidence rates in males differ from the Netherlands as a whole. PMID- 1594068 TI - [A patient with Salmonella aortitis]. AB - Bacterial aortitis is a rare but serious condition. Even when treated surgically, the prognosis is poor. Prompt diagnosis is mandatory. In the absence of specific clinical signs, radiological assessment by means of ultrasound and CT is most valuable. The treatment of choice is early surgical drainage, debridement and arterial reconstruction, preferably through uncontaminated tissue combined with antibiotic therapy. We report the case of a man aged 80 with Salmonella aortitis in whom the diagnosis of bacterial aortitis was made by means of ultrasound and CT, following which successful intervention was carried out. PMID- 1594069 TI - [Notification of current and former sexual partners of persons infected with HIV: is the time ripe for that?]. PMID- 1594070 TI - [What is the minimal daily acetylsalicylic acid for prevention of vascular diseases and how is it best administered?]. PMID- 1594071 TI - [Morbidity and results of 100 radical hysterectomies performed in an oncology center]. PMID- 1594072 TI - [Morbidity and results of 100 radical hysterectomies performed in an oncology center]. PMID- 1594073 TI - [Minor symptoms in family medicine; keratitis caused by ultraviolet radiation]. PMID- 1594074 TI - [Cholecystectomy, a penny whistle?]. PMID- 1594075 TI - [Treatment possibilities in patients with diabetic neuropathies]. PMID- 1594076 TI - [The treatment of behavior disorders in patients with dementia]. PMID- 1594077 TI - [3-year results of 'gallstone outpatient clinic' in an academic hospital]. AB - On April 1st 1988 an outpatient clinic solely for patients with gallstones was started. 594 patients visited the gallstone outpatient clinic during the first three years of its existence and the data of all these patients were collected and examined retrospectively. Mean age was 49.0 years (SD: 15; range: 20-88), male-female ratio was 0.34 and the majority of patients were symptomatic (86.9%). 60.3% were referred by their general practitioners, 21.7% by another specialist en 18.0% sought help on their own initiative. In 8.1% of the cases there were acute biliary problems and 2.4% had an increased surgical mortality risk. Cholecystectomy was advised in the majority of patients (51.9%), expectant management in 20.2%, analysis was stopped in 2.5% and the others (25.4%) were advised a treatment alternative to cholecystectomy. Medical, but most of all public interest in the different therapeutic modalities for symptomatic cholelithiasis has a trend-sensitive character which is reflected in patterns of referral, diagnostic procedures and therapeutic advice given. PMID- 1594078 TI - [Ultrasonography as initial imaging study can replace roentgen studies under certain circumstances in suspected congenital hip dysplasia]. AB - Sonography of the infant hip is increasingly used in the investigation of congenital dysplasia of the hip (CDH). It tends to replace the radiological investigation, which was the common method up till now. In this study sonography and radiological investigation were compared for 255 patient (510 hips), who had been referred to the orthopaedic surgeon on the presumption of CDH. For the sonography the predictive value of a negative finding was 99% (95% CI: 99-100%). The predictive value of a positive finding was 87% (95% CI: 78-95%). Specificity was high: 98% (95% CI: 97-99%); sensitivity lower: 95% (95% CI: 90-100%). Our conclusion is that sonography can replace the radiological investigation if it shows a normal result, for an infant older than 3 months. Additional radiological investigation is necessary if the sonography is abnormal. For infants under 3 months of age the investigation should be repeated at the age of 3 months, at any rate in case of doubt. PMID- 1594079 TI - [Congenital intestinal lymphangiectasis]. AB - We discuss a newborn with congenital intestinal lymphangiectasia. Primary intestinal lymphangiectasia is a rare disease which represents a congenital disorder of mesenteric lymphatics and is associated with typical clinical signs. The diagnosis can be made on the basis of the typical histological findings in the endoscopic biopsies, the laboratory findings and the radiographic findings. Treatment is palliative by introduction of medium chain triglycerides and by restricting the dietary fat intake. Substitution therapy may be necessary. The longer-term prognosis appears to be good. PMID- 1594080 TI - [Moscow chronicle, February 1992]. PMID- 1594081 TI - [Medical activities under adverse conditions. Stimezo International]. PMID- 1594082 TI - [The reflex hammer]. AB - When Erb began to study the knee jerk around 1870 he was able to use the percussion hammer for this purpose. Whereas percussion nowadays is performed with bare fingers, every physician carries a reflex hammer in his bag. Many varieties of reflex hammer have been developed. Their distribution today depends on their use by different schools. The origins and development of the most popular contemporary reflex hammers in English, French and German speaking countries are described. PMID- 1594083 TI - [Neurosurgical treatment of lumbar stenosis. A review of the literature]. AB - Low back pain and claudicatio spinalis are typical for spinal stenosis. Neuroradiological diagnosis is best accomplished by a myelogram. The operative results in patients with a lumbar spinal canal stenosis are successful in 85.5%. Radicular pain responds better than lumbar pain. Severe complications such as new persistent neurological deficits are rare. If the operation is performed early the results are usually better than with delayed surgery. The decompression should be adapted to the type and extent of the stenosis. Additional removal of the disc as well as severe damage to the facet joints increases the risk of postoperative instability. PMID- 1594084 TI - [Clinical aspects of early summer meningoencephalitis in Styria]. AB - 117 cases of clinically manifest tick-borne encephalitis (TBE) in Styria, Austria, the years 1987 to 1990 are reported in terms relevant anamnestic data, clinical findings (meningitis, meningoencephalitis, meningoradiculitis) and course. The geographic distribution corresponds to the known endemic areas for TBE in Styria. We found a significant decrease of incidence. The prognosis of the disease was benign in general; more than 80% ran a course free from complications. A small proportion (5%), however, suffer from severe residual handicap. These patients are subsumed under the group of meningo-radiculitides. Two patients (1.8%) acquired the disease despite having been vaccinated regularly. PMID- 1594085 TI - [Multiple sclerosis mortality 1973-1987 in Baden-Wurttemberg in comparison with socio-geographical variables]. AB - Mortality due to MS in the State of Baden-Wurttemberg (south-west Germany) during the years 1973-1987 was studied in its geographical distribution for a possible association with selected sociogeographic indices for that period. The overall rate for Baden-Wurttemberg (1.3/100,000) was lower than in the neighbouring state of Hesse (1.5/100,000). A relative excess of cases was found in the highland region of the Swabian Alps. In multivariate analysis, correlations were found with the characteristics "forest area/inhabitant", "oat cultivation" and "concentration of polyaromatic hydrocarbons in the drinking water", whereas climate and height above sea-level were not associated. These findings require replication elsewhere. PMID- 1594086 TI - [Intrathecal immune response in meningeosis neoplastica: IgG, IgM, oligoclonal bands and cytokines]. AB - Owing to improved systemic control of widespread malignancy, neurological complications have become a major outcome factor and determinant of life quality in oncological patients. While solitary cerebrospinal metastases are often amenable to surgical and radiological treatment, the management of diffuse leptomeningeal neoplasia, mostly using combined radiochemotherapy, is still very difficult. Immunomodulative approaches represent a therapeutic alternative with increasing potential. We have analysed the natural immune response to leptomeningeal tumor invasion in 43 Patients by assessing cerebrospinal fluid (CSF) levels of albumin, IgG, IgM, interleukins (IL) 1, 2, 4 and 6, soluble IL-2 receptor (sIL-2R), interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and the tumor markers, carcinoembryonic antigen (CEA) and alphafetoprotein (AFP). In most patients, either elevated IgG index, IgM index, CSF IL-6, or detection of CSF oligoclonal immunoglobulin bands indicated a host reaction against tumor cells. IL-1, IL-2, and IL-4 were never detected in CSF or serum. sIL-2R and IFN gamma were rarely detected and were not associated with specific malignancies. CSF TNF alpha was only detected in melanoma patients and may be a specific indicator of that neoplasm. No correlation was found between levels of the tumor markers, CEA and AFP, and parameters of the immune response such as IgG, IgM or IL-6. The demonstration of intrathecal immune activation in a majority of patients with leptomeningeal neoplasia may offer a new option for immunomodulative oncological therapy. PMID- 1594087 TI - [Cerebrospinal fluid cytology in meningeal invasion of leukemia and malignant lymphoma. Reliable diagnosis by immunocytochemistry]. AB - Cerebrospinal fluid cytology was performed in 64 patients who were suspected of having a meningeal infiltration of malignant lymphoma or leukemia. Conventional staining with May Grunwald Giemsa revealed a positive result in 51 cases, and a negative result in one case. In 4 cases diagnosis was hampered by blood contamination or a lack of CSF cells. In the remaining 8 cases with doubtful cytologic specimens, additional immunocytochemic staining allowed definite diagnosis. In 5 of these cases malignancy was confirmed, while in the remaining 3 an inflammatory cell pattern was found and later confirmed by follow-up. In summary, immunocytochemistry was essential for definite diagnosis in 12% of CSF cell specimens suspected of leukemia or malignant lymphoma. It may be concluded that immunocytochemistry in CSF cytology is a valuable tool for enhancement of diagnostic reliability. PMID- 1594088 TI - [The Miller-Fisher syndrome. Report of 5 cases]. AB - Miller Fisher's syndrome is characterized by the symptomtrias of ophtalmoplegia, ataxia and areflexia. Five cases of Miller Fisher syndrome are presented.; the nosological position of this disorder is reviewed. Involvement of brainstem is present in some cases--but obviously facultative. PMID- 1594089 TI - [Garcin syndrome. Clinical aspects and diagnosis of a rare cranial nerve syndrome with special reference to computerized tomography and nuclear magnetic resonance image findings]. AB - Garcin syndrome is an ipsilateral step-by-step deterioration of all 12 brain cranial nerves, first described in 1927. The underlying cause is usually a sarcoma or carcinoma of the skull base. The pathogenesis of the Garcin syndrome is chiefly determined by the slow localized growth of these tumors, rather than by their histology and primary localisation. The prognosis is as a rule unfavourable. The findings on computed and magnetic resonance tomography are important for an early diagnosis. Two cases of Garcin syndrome are reported, one of which was probably due to a tonsillar carcinoma, while the other was caused by a mucinous adenocarcinoma of the nasopharynx. PMID- 1594090 TI - [Acute plexus lesions in heroin dependence]. AB - A wide spectrum of acute and chronic neurological syndromes are associated with heroin addiction. We report two cases with acute brachial/lumbar plexus lesions, with details of the clinical findings, diagnostic procedures and therapy. Possible causes are allergic or toxic reactions to heroin or added substances, as well as nerve compression due to local muscle swelling in connection with rhabdomyolysis. The extent of paresis which occurs is also determined by this compression. PMID- 1594091 TI - [Familial incidence of multiple, mainly spinal meningiomas]. PMID- 1594092 TI - [Noninvasive temporary cardiac pacemaker in neurologic intensive care patients]. AB - The need for temporary cardiac pacing is not unusual in neurocritical patients, due either to disorders of the autonomic nervous system or to concomitant cardiac disease. Mostly, intravenous devices are used. However, intravenous pacing is not without risks, and requires skill and experience when done in emergency cases. We therefore tried a technique of non-invasive, transcutaneous cardiac stimulation on eight patients, for all of whom it proved safe and effective. The only observed side-effect was minor discomfort in conscious patients. PMID- 1594094 TI - [Depression and its pharmacologic treatment. A symposium. Rostock, 19 October 1991]. PMID- 1594093 TI - [Current aspects in discussion of eosinophilia-myalgia syndrome]. PMID- 1594095 TI - Synaptic pathology in Alzheimer's disease: immunological data for markers of synaptic and large dense-core vesicles. AB - We have analysed several markers for small synaptic vesicles (synaptin synaptophysin, p65 and SV2) and large dense-core vesicles (chromogranin A, secretogranin II/chromogranin C) in the brains of patients with Alzheimer's disease, and normal controls by immunoblotting and immunohistochemistry. In comparison to age-matched controls the levels of all three synaptic vesicle markers were decreased in temporal cortex of Alzheimer patients. On the other hand, the levels of chromogranin A were increased, and those of secretogranin II lowered. This resulted in a significant increase of the ratios of chromogranin A to synaptophysin, p65 or SV2 and of that for chromogranin A to secretogranin II. These increases were significantly correlated to clinical severity of dementia and extent of neuropathological changes. By immunohistochemistry a high percentage of senile plaques was found to contain chromogranin A-reactive dystrophic neurites, whereas synaptophysin reactivity within plaques was rare. These results indicate that the number of synaptic vesicles is lowered in Alzheimer's disease, and that one component of large dense-core vesicles, i.e. chromogranin A, is elevated. We, thus, suggest that in Alzheimer's brain distinct changes occur for both types of synaptic organelles. PMID- 1594096 TI - Calretinin in rat brain: an immunohistochemical study. AB - Calretinin is a calcium-binding protein related to calbindin-D28k; both are present in different though overlapping sets of neurons in brains of birds and mammals. We describe in detail the pattern of calretinin immunoreactivity in the rat brain. As in chick brain, calretinin immunoreactivity is abundant in various sensory pathways (particularly certain cells and fibres of the cochlear nuclei and olfactory bulb), in the heterogeneous parts of the brainstem and in parts of the hypothalamus. Many primary sensory fibres are strongly positive. Major groups of calretinin-positive neurons also include the thalamic reticular nucleus, triangular septal nucleus, lateral mammillary nucleus and substantia nigra pars compacta. Many other calretinin-positive cells are recognizable as local inhibitory neurons. Calretinin is absent from all but a few cells in the cerebral cortex, and is never found in motor neurons. There are also some distinctive positive structures whose identity is uncertain, notably irregular "shells" of cells and fibres around the thalamus and in the amygdala and an unnamed cell type in the vestibulocerebellum. PMID- 1594097 TI - Prenatal development of calbindin immunoreactivity in the dorsal thalamus of the rat. AB - The distribution of calbindin immunoreactivity was studied in the developing rat dorsal thalamus at embryonic days 14, 16, 18 and 20. At early stages (days 14 16), calbindin is expressed throughout the dorsal thalamic cell mass. Most intense labeling occurs in cells adjacent to the ventricular surface, in a spatial gradient reflecting the well-known outside-in generation pattern. Between days 16 and 20, calbindin-positive periventricular cells are redistributed in the dorsal thalamus according to two different patterns. They first become oriented tangentially within the periventricular layer, and diminish in number at the central locus where midline thalamic fusion occurs at 18 days. Periventricular calbindin immunoreactivity becomes restricted to a ring of late-born cells surrounding the gray commissure. Recognizable portions of this ring-shaped primordium will mature forming n.paratenialis, n.reuniens, n.paraventricularis, and n.subparafascicularis magnocellularis. Simultaneously, a massive contingent of radially-oriented, fusiform, calbindin-positive young neurons extends from the periventricular ring-shaped aggregate to the lateral brain surface at the caudoventral pole of the dorsal thalamus at embryonic days 17/18. These cells surround the primordium of the medial geniculate body, participating in the constitution of its marginal zone, and invade the lateral posterior nucleus, accumulating within its caudomedial part. Other portions of this stream form the parvocellular subparafascicular nucleus and the peripeduncular nucleus. The observed patterns of calbindin expression suggest that dorsal thalamic postmitotic neurons transiently express the marker during initial phases of axogenesis, whereas a specific, late-born population expresses calbindin continuously into adulthood. This late subpopulation displays migratory behavior, and finally subdivides into several nuclei of the mature midline, superficial and posterior thalamus. PMID- 1594098 TI - Thalamic connections of the second somatic sensory area in cats studied with anterograde and retrograde tract-tracing techniques. AB - The thalamic connections of the second somatosensory area in the anterior ectosylvian gyrus of cats have been investigated using the retrograde tracer horseradish peroxidase and the anterograde tracer Phaseolus vulgaris leucoagglutinin. Horseradish peroxidase was injected iontophoretically in several somatotopic zones of the second somatosensory area map of six cats. Sites of horseradish peroxidase delivery were identified preliminarily by recording with microelectrodes the responses of neurons to skin stimulation. Phaseolus vulgaris leucoagglutinin was iontophoretically injected within the ventrobasal complex (one cat) or in the posterior complex (one cat). Horseradish peroxidase injections into cytoarchitectonic area SII retrogradely labeled neurons in the ipsilateral ventrobasal complex and in the posterior complex. Counts of labeled neurons from the ipsilateral thalamus showed that the overwhelming majority of horseradish peroxidase-labeled neurons were in the ventrobasal complex (96.3 96.9%) and few were in the posterior complex (3.1-3.7%). Neurons labeled in the ventrobasal complex were observed throughout the anteroposterior extent of the nucleus, while their mediolateral distribution varied with the site of horseradish peroxidase delivery in the body map of the second somatosensory area, which indicates that the projections from the ventrobasal complex to the second somatosensory area are somatotopically organized. In the cat in which the horseradish peroxidase injection involved both the second somatosensory area proper and the second somatosensory area medial, which lies in the lower bank of suprasylvian sulcus, labeled neurons were almost as numerous in the ventrobasal complex as in the posterior complex. Phaseolus vulgaris leucoagglutinin injected in the ventrobasal complex anterogradely labeled thalamocortical fibers in the ipsilateral anterior ectosylvian gyrus. In this case, patches of labeled fibers and terminals were distributed exclusively within the cytoarchitectonic borders of the second somatosensory area proper. Labeled terminals were numerous in layer IV and lower layer III, but terminal boutons and fibers with axonal swellings, probably forming synapses en passant, were frequently observed also in layers VI and I. Injection of Phaseolus vulgaris leucoagglutinin in the posterior complex labeled thalamocortical fibers in two distinct regions in the ipsilateral anterior ectosylvian gyrus, one lying laterally and the other medially, which correspond, respectively, to the fourth somatosensory area and the second somatosensory area medial. In both areas the densest plexus of labeled fibers and axon terminals was in layer IV and lower layer III, but numerous labeled fibers and terminals were also observed in layer I. In this case, only rare fragments of labeled fibers were present in second somatosensory area proper, but no labeled terminals could be observed. PMID- 1594099 TI - Specific effects of beta-endorphin infused into the amygdala on sexual behaviour in the male rat. AB - Bilateral intra-amygdaloid infusions of 0, 20, 60, 120 and 200 pmol beta endorphin were administered to sexually experienced male rats in a Latin-square design. Sixty, 120 and 200 pmol beta-endorphin significantly decreased preintromission investigation rate and increased intromission latency with an oestrous female. No other effects on the male rats' sexual behaviour were produced. beta-Endorphin-induced effects on preintromission investigation and intromission latency were naloxone reversible (5 mg/kg, i.p.). Similar doses of intra-amygdaloid beta-endorphin had no effect on aggressive interaction with another, strange, male behaviour and similar doses of intra-amygdaloid corticotropin-releasing factor had no effect on sexual behaviour. Thus, there was both behavioural and chemical specificity of intra-amygdaloid beta-endorphin induced effects on male sexual behaviour. Bilateral 60 pmol beta-endorphin infusions into the caudate-putamen had no effects on male sexual behaviour, demonstrating anatomical specificity of the intra-amygdaloid-induced effects. Basolateral excitotoxic lesions did not prevent the behavioural effects of intra amygdaloid beta-endorphin infusions. These results demonstrate that intra amygdaloid beta-endorphin specifically suppresses the precopulatory phase of male rat sexual behaviour but leaves the execution of the copulatory series intact once it has been initiated. This effect appears to be mediated via the corticomedial amygdaloid region. The change in precopulatory behaviour suggests that beta-endorphin may interfere with the processing of sensory information from the female, thus delaying appropriate initiation of the copulatory series. PMID- 1594100 TI - The effects of beta-endorphin infusions into the amygdala on visual and olfactory sensory processing during sexual behaviour in the male rat. AB - Sexually experienced male rats infused bilaterally into the amygdala with 60 pmol beta-endorphin show decreased rate of precopulatory investigation of the female and delayed intromission latency, but copulation is left unaltered. Such males are still able to discriminate between the odours of bedding from receptive and unreceptive females, demonstrating that beta-endorphin does not impair the ability to detect sexually relevant odours. Preventing visual cues emitted by females during proceptive behaviour (by treating them with haloperidol) delayed intromission latency but had no effect on preintromission investigation. Intra amygdaloid beta-endorphin exacerbated the effects of this treatment on the intromission latency. Inducing anosmia in males (by applying zinc sulphate solution to the olfactory mucosa) decreased their anogenital investigation and delayed their intromission latency. These effects were not enhanced by intra amygdaloid beta-endorphin. Allowing males to investigate and initiate the first intromission prior to intra-amygdaloid infusion had no effects on subsequent intromissions. However, if following an intromission with one female and an infusion of beta-endorphin, the male was presented with an unfamiliar female then the effects of intra-amygdaloid beta-endorphin on investigation and intromission returned. These results suggest that beta-endorphin in the amygdala interferes with the processing of female-specific olfactory information. Without this processed information, classification of the female as a sexual stimulus may be impeded and thus sexual arousal delayed. PMID- 1594102 TI - Mechanisms of supraspinal correction of scratching generator. AB - The influences of signals in descending systems on the parameters of scratching generator activity were studied on decerebrate immobilized cats. It was shown that phasic electric stimulation of descending systems evoked certain phase dependent reorganization of the parameters of scratching generator efferent activity. Maximum increase in scratching cycle duration during electric stimulation of Deiters' nucleus, red nucleus and pyramidal tract is observed during stimulation in the first half of aiming phase. Stimulation in the second half of aiming phase and at the beginning of scratching jerk phase virtually does not change the scratching cycle duration. Maximum increase in scratching cycle duration during electric stimulation of the nucleus reticularis gigantocellularis is observed in the second half of aiming phase. Electric activation of descending pathways during aiming phase increases its intensity and decreases the intensity of scratching jerk phase. Activation of descending pathways during scratching jerk phase increases its intensity and virtually does not change the aiming phase intensity. Influences of electric activation of descending systems on scratching generator work reveal dependence on limb position. They are increased when the limb is deflected to the rear and are decreased during over-aimed position. Decerebellation leads to a decrease of scratching generator activity parameters rearrangement under influence of electric stimulation of the red nucleus and nucleus reticularis gigantocellularis, and to its increase during Deiters' nucleus stimulation. On the basis of these results the principles of supraspinal correction of scratching generator work are discussed. PMID- 1594101 TI - Selective presynaptic insectotoxin (alpha-latroinsectotoxin) isolated from black widow spider venom. AB - A homogenous protein of 120,000 mol. wt isolated from black widow spider (Lactrodectus mactans tredecimguttatus) venom and referred to as alpha latroinsectotoxin was highly potent (4 nM) in the induction of an increase of the frequency of miniature excitatory postsynaptic potentials in blowfly (Calliphora vicina) larvae neuromuscular preparations. In the frog nerve ending, however, even 50 nM alpha-latroinsectotoxin failed to affect transmitter release. Pretreatment of insect preparations with alpha-latrotoxin or frog preparations with alpha-latroinsectotoxin did not prevent the specific effect of consequent applications of alpha-latroinsectotoxin (insect) and alpha-latrotoxin (frog), respectively. The binding of labelled [125I]alpha-latroinsectotoxin to insect and [125I]alpha-latrotoxin to bovine membrane preparations was saturable and highly specific. The presynaptic effect, but not the binding of alpha-latroinsectotoxin, was dependent on the presence of divalent cations in the external medium. Mg2+ could readily substitute for Ca2+ and increase of transmitter release induced by alpha-latroinsectotoxin also occurred in Ca(2+)-free solutions. Pretreatment of preparations with 300 micrograms/ml concanavalin A completely abolished both the presynaptic effect of alpha-latroinsectotoxin and its binding to insect membrane preparations. Thus, the phenomenology of alpha-latroinsectotoxin action on insects resembles in general that described for the action of alpha-latrotoxin on vertebrates. The selectivity of alpha-latrotoxin and alpha-latroinsectotoxin seems to be due to differences in the structure of neurotoxin receptors in nerve endings of vertebrates and insects, although the mode of presynaptic action has a great deal in common. PMID- 1594103 TI - The constrained control of force and position in multi-joint movements. AB - In many arm or leg movements the hand or foot has to exert an external force on the environment. Based on an inverse dynamical analysis of cycling, it is shown that the distribution of net moments in the joints needed to control the direction of the external force is often opposite to the direction of joint displacements associated with this task. Kinetic and kinematic data were obtained from five experienced cyclists during ergometer cycling by means of film analysis and pedal force measurement. An inverse dynamic analysis, based on a linked segments model, yielded net joint moments, joint powers and muscle shortening velocities of eight leg muscles. Activation patterns of the muscles were obtained by means of surface electromyography. The results show that the transfer of rotations in hip, knee and ankle joints into the translation of the pedal is constrained by conflicting requirements. This occurs between the joint moments necessary to contribute to joint power and the moments necessary to establish a direction of the force on the pedal which allows this force to do work on the pedal. Co-activation of mono-articular agonists and their bi-articular antagonists appear to provide a unique solution for these conflicting requirements: bi-articular muscles appear to be able to control the desired direction of the external force on the pedal by adjusting the relative distribution of net moments over the joints while mono-articular muscles appear to be primarily activated when they are in the position to shorten and thus to contribute to positive work. Examples are given to illustrate the universal nature of this constrained control of force (external) and position (joint). Based on this study and published data it is suggested that different processes may underlie the organization of the control of mono- and bi-articular muscles. PMID- 1594104 TI - Time-dependent changes in the activity of opioid systems in the spinal cord of monoarthritic rats--a release and in situ hybridization study. AB - The activity of the endogenous opioid systems was analysed in the spinal cord of rats 12 h, one, five or 14 days after injection of the Freund Adjuvant into the hind limb sole. The tissue level of immunoreactive Met-enkephalin-Arg6-Gly7-Leu8, a peptide derived from proenkephalin, started to rise 12 h after Freund Adjuvant inoculation and remained enhanced until day 14. The spontaneous release of the immunoreactive Met-enkephalin-Arg6-Gly7-Leu8 was also elevated at all the examined time points, the peak occurring on day 1. No changes were observed in the stimulated release except on day 14, when the peptide release was decreased. The proenkephalin messenger RNA level was enhanced at all the time points on the ipsilateral side of the spinal cord in laminae I-II, whereas in lamina V an increase was observed only on days 1 and 5. An increase in the proenkephalin messenger RNA level on the contralateral side was observed only in laminae I-II and only on days 1 and 5. The tissue level of immunoreactive alpha-neoendorphin, a peptide derived from prodynorphin, was significantly increased on days 5 and 14. The spontaneous immunoreactive alpha-neoendorphin release from spinal cord slices was elevated at all the time points studied, whereas the stimulated release of the peptide was strongly increased 12 h after Freund Adjuvant inoculation but gradually declined on the following days. An in situ hybridization study showed that the prodynorphin messenger RNA level in laminae I II was increased at all the examined time points.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594105 TI - Expression of provasopressin gene during ontogeny in the hypothalamus of developing mice. AB - We investigated the ontogeny of provasopressin gene expression in neurosecretory neurons of the supraoptic and paraventricular nuclei of developing mice by semi quantitative in situ hybridization and immunohistochemical techniques in combination with stereometry of vasopressin-immunoreactive neurons. Provasopressin mRNA was detected in paraffin sections using a mixture of radiolabeled synthetic oligonucleotide probes complementary to the mRNA loci encoding vasopressin (2-9) and vasopressin neurophysin (1-8). Vasopressin immunoreactivity was located with a polyclonal anti-vasopressin antiserum and a monoclonal anti-vasopressin-neurophysin antibody either with or without enhancing technique for the diaminobenzidine reaction. Autoradiographic hybridization signals that indicate the localization of provasopressin mRNA were first detected on embryonic day 15 in the supraoptic nucleus and embryonic day 18 in the paraventricular nucleus. Vasopressin immunoreactivity was first found in the median eminence on embryonic day 14, and then in the supraoptic and paraventricular nuclei on embryonic days 15 and 16, respectively. The provasopressin mRNA levels were markedly increased in both the supraoptic and the paraventricular nuclei just after birth. The immunoreactivity of vasopressin neurons was drastically decreased in both nuclei on postnatal days 1 and 2, suggesting marked vasopressin release in the neonates. Cross-sectional areas of vasopressin-immunoreactive somata and their cell nuclei gradually increased in both the supraoptic and the paraventricular nuclei during the perinatal period by day 5, and then attained adult size between days 10 and 20. During this phase, the level of provasopressin mRNA remained low compared with that in the adult magnocellular neurosecretory cells. These results indicate that the expression of provasopressin gene is markedly increased in both the supraoptic and the paraventricular nuclei soon after birth. Secretory activity of vasopressin neurons is elevated in neonatal mice. Vasopressin may have an important osmoregulatory role in neonatal mice undergoing drastic changes in water metabolism following birth. PMID- 1594106 TI - Monoclonal antibodies reveal molecular differences between terminal fields in the rat dentate gyrus. AB - We have derived a number of monoclonal antibodies which detect molecular differences correlating with the afferent inputs to the molecular layer of the adult rat hippocampal dentate gyrus. One group, dubbed OM-1 to OM-4, strongly stain the outer zone of the molecular layer, which receives its major innervation from the ipsilateral entorhinal cortex. A second group, IM-1 and IM-2, show a complementary pattern and preferentially stain the inner molecular layer, which receives inputs from the ipsilateral and contralateral hippocampus. These antigens are not, however, restricted to these layers, being found outside the hippocampus in several other areas of neuropil in the adult brain. In the developing brain the IM-1 antigen appears ubiquitously from the earliest age studied, embryonic day 12. Within the dentate gyrus, its restriction to the inner terminal field of the molecular layer only occurs during the second postnatal week. In contrast, OM staining appears only sparsely and late in the prenatal brain, appearing in developing cortical white matter between embryonic days 18 and 20. The outer dentate molecular layer becomes OM-positive from birth onwards, corresponding to the time of arrival of entorhinal axons during the first postnatal week. These two groups of monoclonal antibodies recognize a number of different glycoproteins. Ultrastructural immunohistochemistry shows they are cell surface molecules, and as such may be involved in the recognition events required for the establishment of specific patterns of neuronal connectivity. PMID- 1594107 TI - c-fos protein-like immunoreactivity: distribution in the human brain and over expression in the hippocampus of patients with Alzheimer's disease. AB - c-fos protein-like immunoreactivity was investigated in the human brain post mortem, using a polyclonal antiserum raised against the N-terminal conserved peptide of c-fos protein. Immunostaining was found in the cerebral cortex, hippocampus, striatum, thalamus and cerebellum but not in the upper brainstem and the adrenal gland. c-fos-like immunoreactivity predominated in neuronal elements, but was also observed in neuropil and glial cells. In addition to a nuclear localization, the staining could be seen in neuronal dendrites (i.e. in the pyramidal cells of hippocampus or in some cortical areas). In order to analyse the effect of brain injury on c-fos expression, the characteristics of the immunostaining were analysed in the hippocampus of patients deceased with Alzheimer's disease known to be associated with a preferential vulnerability of the pyramidal neurons. No staining was observed in the senile plaques or in neurofibrillary tangles, the histopathological stigmata of the disease. Densitometric measurement of the intensity of c-fos-like staining revealed a significant increase in the hilus, the fimbria and the CA1 field of the pyramidal layer in brains of patients with Alzheimer's disease compared to controls. These modifications may result from a suffering stage of hippocampal cells or from a compensatory mechanism in the still surviving neurons not yet affected by the pathological process. PMID- 1594108 TI - [Address of Professor A. Basile at the end of the inaugural ceremony]. PMID- 1594109 TI - [Minutes of the Biennial Congress of the Italian Section of the International College of Surgeons organized by Professor Salvatore Navarra in honor of Professor Attilio Basile]. PMID- 1594110 TI - Anaerobic infection in polytrauma. PMID- 1594111 TI - [Renal calculosis: current and future therapeutic aspects]. PMID- 1594112 TI - [Rationalization of the use of blood in surgery]. PMID- 1594113 TI - Long follow-up changes of the saphenous vein transplant. PMID- 1594114 TI - [Evolution of surgical therapy in mitral stenosis]. PMID- 1594115 TI - Advances in adjuvant chemotherapy for colon cancer. PMID- 1594116 TI - [Current status of heart transplantation]. PMID- 1594117 TI - [Prevention of pulmonary embolism by caval filters]. PMID- 1594118 TI - [Surgery and acquired immunodeficiency syndrome (AIDS)]. PMID- 1594119 TI - [The surgeon and the terminal patient]. PMID- 1594120 TI - Ventral incisional hernia. PMID- 1594121 TI - [Reflux esophagitis and fixed intrathoracic cardia. Surgical treatment using intrathoracic hemivalve]. PMID- 1594122 TI - [Kidney transplantation: 21-year experience at the Polyclinic of Milan]. PMID- 1594123 TI - [Colovesical fistulas caused by diverticular disease]. PMID- 1594124 TI - [Diagnostic timing in complicated and uncomplicated diverticular disease]. PMID- 1594125 TI - [Epidemiology and physiopathology of diverticular disease of the colon]. PMID- 1594126 TI - [Therapy of inflammatory complications of sigmoid diverticulosis]. PMID- 1594127 TI - [Primary gastric lymphoma. Role of surgery]. PMID- 1594128 TI - [Prognostic significance of clinical factors and histological data in gastric lymphomas]. PMID- 1594129 TI - [Staging and therapy of primary gastrointestinal lymphomas]. PMID- 1594130 TI - [Diagnosis of primary gastric lymphomas]. PMID- 1594131 TI - [Diagnosis and treatment of pancreatic pseudocysts]. PMID- 1594132 TI - [Acute pancreatitis: treatment of immediate and late complications]. PMID- 1594133 TI - [Acute pancreatitis: elements of physiopathology]. PMID- 1594134 TI - [Imaging diagnosis in the monitoring of acute pancreatitis]. PMID- 1594135 TI - [Hospital infections: principles of preoperative prophylaxis]. PMID- 1594136 TI - [Nosocomial infections in geriatric surgical patient]. PMID- 1594137 TI - [Preoperative prevention of nosocomial infections]. PMID- 1594138 TI - [Systems of hospital infection surveillance: analysis and preliminary experiences]. PMID- 1594139 TI - [History of nosocomial infections]. PMID- 1594140 TI - [Nosocomial infections: epidemiology and risk factors]. PMID- 1594141 TI - [Prevention of infections caused by bladder catheterization]. PMID- 1594142 TI - Exploring poisoning data collection systems. PMID- 1594143 TI - Do-not-resuscitate and the anesthesiologist. PMID- 1594144 TI - The do-not-resuscitate order in a nursing home: patient's choice or staff's decision. AB - An 86-year-old woman in a residential health care facility suffered a massive stroke; immediate intubation was performed, she was transferred to a nearby hospital where she died two months later. Within 48 hours of this event, three mentally competent residents and one family member on the unit requested a do-not resuscitate order. They, along with the seven other mentally competent and non terminal residents on the unit, participated in a questionnaire survey, the purpose of which was to elicit information on DNR attitudes. Only one respondent requested cardiopulmonary resuscitation. All insisted that do-not-resuscitate decisions were theirs alone to make. A staff questionnaire was given to 81 employees having many years of health care experience. Most had witnessed death and cardiopulmonary resuscitation and knew of its poor outcome. However, 51% were very willing to participate in cardiopulmonary resuscitation, and 65% thought cardiopulmonary resuscitation was worthwhile in residential health care facilities. Furthermore, 56.8% thought that families should participate in the decision. The dichotomy between residents' wishes and staff perceptions merits recognition and further study. PMID- 1594145 TI - Drug poisoning patterns: the Albany experience, 1978 and 1988. AB - This study retrospectively compares the demography and patterns of poisonings and their local variations among patients admitted to Albany Medical Center Hospital in the years 1978 and 1988. An increase in the number of admissions during this period of time, and an apparent substantial change in the pattern of poisonings was observed; in addition, the gender difference observed in 1978 disappeared. Although street drugs were a common source of poisoning, the resulting morbidity and mortality was low. The use of extracorporeal drug removal procedures appears to have declined in this institution in the two years evaluated. PMID- 1594146 TI - The golden years or the wasteland. PMID- 1594148 TI - Primary and secondary aortoenteric fistula and thoracic aortic aneurysm. PMID- 1594147 TI - Ethical considerations concerning the HIV-positive physician. PMID- 1594149 TI - Metastatic hemangiopericytoma of the breast. PMID- 1594150 TI - Spontaneous rupture of the spleen as the initial manifestation of acute myeloid leukemia. PMID- 1594151 TI - Resolution of fungal peritonitis after early catheter removal without amphotericin B therapy. PMID- 1594152 TI - The physician and the poor. PMID- 1594153 TI - OSHA exposure control plan due now. PMID- 1594154 TI - A woman's place. AB - Getting through dental school is only half the battle for a woman. There are a host of new frustrations when she enters the profession and finds herself battling misconceptions and questions concerning the seriousness of her career. PMID- 1594155 TI - Recessionary dental economics. AB - The economics of dentistry during a recession can be difficult. However, reports for the early stages of the current downturn indicate that the general population continued to increase its expenditures for dental care and that practitioners were able to maintain practice income. PMID- 1594156 TI - Temporomandibular/facial pain. An epidemiological report. PMID- 1594157 TI - Construction of temporary crown for transitional removable partial dentures. AB - Often restoration requires maintaining patient function with the old partial denture while constructing permanent crowns and a new removable prosthesis. The technique described here allows the practitioner to produce temporary crowns to maintain function with the old partial during prosthetic reconstruction. PMID- 1594158 TI - Oral prosthesis and chemosensory taste function. A review of the literature. AB - Denture use may have a negative impact on the ability to taste food, which in turn can jeopardize one's nutritional well-being. It is important that dentists understand the relationship. PMID- 1594159 TI - The 1,717 Most Wanted List. AB - Unlike the people on the FBI's 10 Most Wanted List, the men and women on New York State's 1,717 Most Wanted List are not bad persons, nor are they dangerous criminals. But they are almost as difficult to locate as those on the FBI list. PMID- 1594160 TI - ADA statement on handpieces. PMID- 1594161 TI - Health care reform: dentistry's future. PMID- 1594162 TI - The force of change. PMID- 1594164 TI - Training of physicians for the practice of nuclear medicine, the USA experience. PMID- 1594163 TI - MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In. AB - A novel method for generating monoclonal antibodies against synthetic tumour associated glycoconjugates has been developed. One of these monoclonal antibodies, designated 170H.82, was derived against the TF antigen and has been shown in vitro to have a wide range of reactivity with adenocarcinoma. This antibody has been labelled with 111In and 99Tcm and has been evaluated in pilot clinical trials involving 48 patients with a range of adenocarcinoma. Overall clinical accuracy with the radiolabelled antibody was 92%, with the antibody appearing to have particular clinical utility in gynaecological and breast cancers. Single photon emission computed tomographic (SPECT) imaging was shown to improve the quality of the images and to improve the diagnostic sensitivity. We believe that this unique antibody, labelled with 99Tcm, appears to offer promise for routine clinical use in the evaluation of patients with a range of primary and metastatic adenocarcinoma. PMID- 1594165 TI - A comparison of three commercially available PET imaging systems. AB - Three commercial positron emission tomography (PET) imagers were assessed using the same test protocol (Positron Corporation 'Posicam', Siemens Ecat 951/31 and the Scanditronix PC 4096-15WB). A cylindrical phantom and a 'Jaszczak' phantom both filled with 18F were employed to measure sensitivity, slice uniformity, transaxial and axial resolution and cold rod contrast. The spread of results were as follows: sensitivity varied from 2.08 to 3.73 kcps kBq-1 ml-1 (77-138 kcps microCi-1 ml-1); radial resolution on axis (at 17.5 cm) varied from 5.0 to 5.9 mm (6.7-8.1 mm); tangential resolution ranged from 5.4 to 5.8 mm (6.7-8.6 mm); axial resolution ranged from 4.6 to 11.5 mm (6.6-13.6 mm); contrast in the middle of a 30 mm diameter rod varied from 98 to 93% and for a 5 mm rod from 37 to 22%. The performance of all three systems approximated reasonably well to the manufacturers' published specifications. The most significant differences were found to be in sensitivity, axial resolution and deadtime correction and can be explained by the choice of crystal size and crystal/photomultiplier configuration. PMID- 1594166 TI - Diagnosis of venous leakage by 133Xe corporeal clearance after intracavernous injection of prostaglandin E1 in poorly responding patients. AB - 133Xe corporeal clearance after intracavernous (IC) prostaglandin E1 (PGE-1) injection was assessed in detecting venous leakage (VL) in a group of impotent patients with poor clinical response to PGE-1 injection. 133Xe corporeal washouts were done in the flaccid state and at full erection or at 20 min after the IC injection of 20 micrograms PGE-1 in cases where no full erection occurred in sequence on two separate days. In each case, data were acquired in frame mode after intracorporeal injection on one side of the midline just behind the glans of 0.1 ml, namely, 1-2 mCi (34-74 MBq) 133Xe in saline for 20 min. A time activity curve was generated from the region of interest (ROI) at the site of injection and a computer routine was used to calculate clearance half-time (T1/2) in min and flow rate (Q) in ml per 100 g tissue per min. The data of 20 patients with equivocal response to IC PGE-1 were analysed. Of them, 14 had venous leakage and six had no vascular impairment (NVI). Venous leakage was proved by Doppler analysis, cavernosography after PGE-1, and/or selective arteriography. Twelve of 14 patients with VL had enhanced 133Xe corporeal clearance after PGE-1 with a significant decrease in T1/2 (mean +/- S.D.) from 115.9 +/- 196.0 to 13.3 +/- 13.4 (P less than 0.05) and increase in Q from 2.1 +/- 2.2 to 7.5 +/- 5.6 (P less than 0.01). In contrast, all six patients with NVI had decreased 133Xe corporeal clearance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594167 TI - Clinical and experimental studies on the mechanism of abnormal accumulation in lung scanning with 123I-IMP. AB - To investigate the intrapulmonary kinetics of N-isopropyl-p-I-123-iodoamphetamine (123I-IMP), lung scanning with 123I-IMP was performed in patients with various lung disorders. Compared with the normal lung field, abnormal accumulation of 123I-IMP was detected in all patients in delayed imaging performed 24 h after 123I-IMP injection. These sites were within areas of absent or reduced perfusion observed by pulmonary perfusion scanning using 99Tcm-macroaggregated albumin (99Tcm-MAA). A similar phenomenon was seen in additional experiments in rabbits with regional pulmonary arterial hypoperfusion resulting from a balloon catheter induced bronchial occlusion. 123I-IMP accumulation in areas where 99Tcm-MAA images are absent or decreased may be explained by the ability of 123I-IMP to penetrate significantly narrowed microvascular beds with reduced perfusion. Our clinical and experimental results indicate that pulmonary arterial perfusion, particularly hypoperfusion, influence the pulmonary kinetics of 123I-IMP. This compound is a potentially useful non-particulate agent for the assessment of pulmonary arterial perfusion. PMID- 1594168 TI - The detrimental health effects of ionizing radiation. AB - Radiation-induced diseases have long been recognized, but quantifying their incidence, particularly at low doses, is still subject to speculation and differing interpretations of the data. Some of the difficulties are discussed in this paper which summarizes the biological background on which the basic International Commission on Radiological Protection recommendations on radiological protection are based. PMID- 1594169 TI - The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography in patients with coronary artery disease. AB - The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography. PMID- 1594170 TI - Refillable point source for motion correction during first-pass radionuclide angiography. AB - First-pass radionuclide angiography, for the evaluation of ventricular function during peak physiological stress, requires the use of a low-energy point source for correction of motion artifacts. A design for the construction of a refillable 125I point source is presented. PMID- 1594171 TI - A new method for assessing 99Tcm-MDP bone uptake from a bone scan image: quantitative measurement of radioactivity in global skeletal regions of interest. AB - Bone uptake of 99Tcm-MDP was evaluated 4 h after injection in 27 normal subjects aged 23-50 years by gamma camera measurement of the activity in whole skeleton regions of interest (ROIs) in anterior and posterior projection. The mean global skeletal uptake (GSU) (% of whole-body activity in both projections measured 30 s after injection) was 33.5 +/- 4%. The standard urinary excretion method (whole body retention, WBR) gave a mean bone uptake value of 31.5 +/- 4%. A significant correlation (r = 0.570; P less than 0.002) was found between GSU and WBR. The mean bone-to-soft tissue ratio (B/S index) was 3.0 +/- 1.1. It is suggested that this direct, external counting method provides a way of obtaining both a qualitative and a semiquantitative evaluation of bone uptake with a single tracer administration in a routine bone scan. Investigation of its use in the assessment of bone involvement in low and high turnover bone diseases is now under way. PMID- 1594172 TI - Using the micro to train personnel in the use of a patient care information system. PMID- 1594173 TI - Using IVD for hospital orientation. PMID- 1594174 TI - Interactive video integration: how one school of nursing got started. PMID- 1594175 TI - Preparing for the next 5 years of instructional technology (cont'd). PMID- 1594176 TI - Making lemonade: surmounting the LRC budget cuts. PMID- 1594177 TI - Using groupware: meeting/collaboration software. PMID- 1594178 TI - An electronic community for health care. PMID- 1594179 TI - Factors that influence successful integration of IVD technology in nursing. PMID- 1594180 TI - [Pathologic and ophthalmopathologic findings in holoprosencephaly syndrome]. AB - Report of 3 cases with holoprosencephaly syndrome (1 case of type 5 de Myer and 2 cases of type 1). Pathology and ophthalmic pathology are reported and discussed as well as the classification. PMID- 1594181 TI - Role of diabetes mellitus on the natural history of central retinal vein occlusion. AB - In order to elucidate the role of diabetes mellitus on the natural history of central retinal vein occlusion, we compared two groups of central retinal vein occlusion, one with diabetes mellitus (32 patients) and one without diabetes mellitus (113 patients). The two groups were quite similar with respect to age, sex, systemic hypertension and glaucoma. No fellow eye had proliferative diabetic retinopathy. The diabetic group had angiographically a more ischemic type of central retinal vein occlusion (72%) than the nondiabetic group (39%; p less than 0.002). Diabetics with central retinal vein occlusion should be closely monitored. PMID- 1594182 TI - [Xerophthalmia in liver cirrhosis. Correct diagnosis after 15 years]. AB - The clinical features of xerophthalmia are described in a 60-year-old patient, who was known to have alcoholic cirrhosis. In this patient, vitamin A deficiency, which presumably had been overlooked for 15 years, was confirmed by determination of the serum vitamin A level. After substitutive vitamin A therapy, superficial punctate keratitis and conjunctival xerosis disappeared completely. Although xerophthalmia has only sporadically been described in developed countries, we point out that the possibility of a vitamin A deficiency should also be considered in cases of recurrent conjunctival and corneal lesions. PMID- 1594183 TI - Presence of pseudoexfoliation on clear and opacified crystalline lenses in an aged population. AB - Pseudoexfoliation (PEX) of the lens capsule is a well-known risk factor for open angle glaucoma. Its prevalence is known to increase by age in the same way as prevalence of age-dependent cataract. In the present paper the prevalence of PEX varied from 8.5 to 13.2% increasing by age. Lens opacities were statistically significantly more common in PEX-positive than PEX-negative eyes. The importance of detecting exfoliation from the lens surface is discussed. PMID- 1594184 TI - Sudden against-the-rule astigmatism 6 months after intraocular lens implantation with the Kelman phacoemulsification procedure: 4 of 809 cases. AB - Of 809 eyes that underwent the Kelman phacoemulsification and aspiration (KPE) procedure, we report on 4 patients (0.49%) who developed sudden against-the-rule (AR) astigmatism after intraocular lens implantation. These patients had had with the-rule astigmatism preoperatively to 3 months postoperatively and suddenly developed AR astigmatism 6 months after surgery. To study the development and progression of AR astigmatism in these patients (group A), we compared their 6 month time course with that of 257 patients (group B) with postoperative AR astigmatism. In group A, the degree of astigmatism was not significantly different from group B astigmatism preoperatively (1.03 +/- 0.16 vs. 1.04 +/- 0.04 dptr) and 6 months postoperatively (1.32 +/- 0.13 vs. 1.26 +/- 0.05 dptr). However, 1 week postoperatively, the astigmatism of the 4 cases was much greater (5.72 +/- 0.14 dptr) than that of the others (2.32 +/- 0.07 dptr). These rare 4 cases, which had no other unusual characteristics, are indicative of the importance of a careful follow-up even if the post-KPE course seems uneventful. PMID- 1594185 TI - Combined silicone and fluorosilicone oil tamponade (double filling) in the management of complicated retinal detachment. AB - We evaluated the use of simultaneous double filling with polydimethylsiloxane (PDMS) and fluorosilicone (FSiO) in the repair of complicated retinal detachment in 12 selected cases. Initial retinal reattachment was achieved in all cases. Proliferative vitreoretinopathy (PVR) recurred in 10 patients (83%), 6 of which showed partial retinal detachment. Inferior and superior postoperative residual free spaces were abolished by this procedure, but a new residual fluid space was created, lying horizontally between the bubbles and expanding in a triangular shape nasally to the optic disk and temporally to the macula. Overall, 9 of 10 eyes with postoperative PVR had proliferation involving these areas. These findings support the concept that 'compartmentalization' is of major importance in determining postoperative cell proliferation. PMID- 1594186 TI - Synoptometer analysis of vertical shoot in Duane's retraction syndrome. AB - Vertical deviation of the affected eye caused by horizontal change of gaze was measured with a synoptometer in 5 cases of Duane's retraction syndrome type III. Step-by-step measurement clearly showed two types of incomitance patterns, i.e. upshoot and up- and downshoot in adduction. The former suggests a paradoxical synergistic innervation between the medial rectus and superior rectus muscles, and the latter suggests an abnormal vertical movement of the lateral rectus muscle over the globe on elevation or depression of the eye. Recession of the lateral rectus muscle, however, reduced the vertical deviation regardless of the incomitance pattern. PMID- 1594187 TI - Increased sensitivity with decreased numbers of test points and decreased test field size in automated perimetry of normal subjects. AB - Mean sensitivity (MS) was compared among programs with different numbers of test points and different test field sizes with an automated perimeter in normal subjects. The programs tested were designed by the program Sargon. Within a 10 degree visual field the MS was significantly higher with fewer test points and with a smaller test field size. The MS between 10 and 25-degree fields increased under the same conditions. Increased MS was found with decreased numbers of test points and decreased test field size within 25 degrees in automated perimetry of normal subjects. PMID- 1594188 TI - Results and implications of high-resolution surface dosimetry of ruthenium-106 eye applicators. AB - The dosimetry of 106Ru/106Rh beta-emitting eye applicators is still inadequate. Manufacturer's specifications of absolute dose rates are loaded with a +/- 30% error, and the relative distribution of activity on the surface is measured on a few points only, using a 3-mm plastic scintillation probe. While reducing the absolute error of dose rate measurements to +/- 15% by a method published earlier, we now present a phantom using small thermoluminescent dosimetry crystals for refined assessment of its distribution over the surface. Evaluation of two applicators revealed a 50% increase in activity in the midperiphery in one and a steep falloff of activity 1 mm within the margin of both specimens. The method and findings are demonstrated in detail and compared to those reported by other authors. PMID- 1594189 TI - Bilateral retinoblastoma. Correlations between age at diagnosis and time course for new intraocular tumors. AB - A retrospective analysis of 355 eyes from 325 patients with bilateral retinoblastoma followed for at least five years was analyzed for the development of new ocular tumors. Eighty-eight eyes (24.8%) developed new tumors with more than 95% of these seen in patients diagnosed before the age of two years. Excluding one patient, no new tumors were seen in patients who were initially diagnosed after 33 months of age. The relative risk for developing new tumors was greater (45.1%) for patients diagnosed within the first six months of life than for patients diagnosed after the age of six months (14.2%). The highest percentage of patients (58%) to develop new tumors were those diagnosed before the age of three months. In patients initially treated before two years of age, new tumors were noted to develop up to 4.5 years later, whereas among eyes diagnosed after the age of two years, 100% of all new tumors were seen before 1.5 years of follow-up. Regardless of the age at diagnosis, however, the upper age limit for new tumor development ranged from 4.0-6.25 years, with a mean of 5.1 years. All new tumors were managed with either photocoagulation/cryotherapy or plaques. PMID- 1594190 TI - Unilateral benign medulloepithelioma associated with bilateral retinal detachment. AB - A two-month-old girl presented with a unilateral benign cystic medulloepithelioma from the ciliary body associated with bilateral retinal non-attachment. The authors discuss the histopathologic findings and the pathogenesis of the congenital retinal non-attachment: are these incidental occurrences or do they arise from a common pathogenetic mechanism? PMID- 1594191 TI - A new look at the management of the oculo-mandibulo-facial syndrome. AB - The authors review the literature on the oculo-mandibulo-facial syndrome and present the case of a six-year-old boy with congenital cataracts, microphthalmos, nystagmus, failure to thrive, dysmorphic features with a tiny pinched nose, mandibular hypoplasia, microstomia, double chin, chronic snoring, recurrent respiratory infections and dental problems. Chronic obstructive sleep apnoea with decreased oxygen saturation was present. Optimal medical management of OMFS patients is described. PMID- 1594192 TI - Recessively inherited, simple optic atrophy--does it exist? PMID- 1594193 TI - Cumulative incidence of retinoblastoma in Riyadh, Saudi Arabia. AB - A survey of all hospitals in the city of Riyadh for retinoblastoma cases presenting during the period 1982-1986 was performed; 22 cases (16 females and six males) were identified. The cumulative live births in the city of Riyadh for the same period numbered 254,780. The authors report the cumulative incidence of retinoblastomas in Riyadh, Saudi Arabia as 1:11580 live births per year. PMID- 1594194 TI - Task and visual performance with contact lenses and spectacles. AB - Previous studies found task and vision performance differences between presbyopic contact lens corrections and distant contact lenses combined with reading spectacles. The present study was designed to compare task and vision performance with single vision contact lenses and spectacles. Eighteen soft (SCL) and seventeen rigid gas permeable (RGP) successful contact lens wearers were examined and fitted with CR-39 spectacles (SPEX) which corrected their distance vision. Their occupational task performance and visual acuity (high contrast, low contrast, low contrast with glare) were measured while they wore their contact lenses and spectacles. The tasks included putting pointers in straws, filing cards in a box, counting letters on a photograph of a VDT screen, and a distance/near fixation task. Visual acuity scores were lower with SCL than with SPEX. Low contrast visual acuity with glare was reduced by 1.36 letters on a 5 letter row (p less than 0.05) for SCL compared to SPEX. No statistically significant differences in performance times were measured between contact lenses and spectacles. None of the error performance differences were statistically significant; however, more errors were made on each occupational task with soft contact lenses compared to spectacles. The findings suggest nearly equivalent task and visual performance with properly prescribed RGP contact lenses and spectacles, and minimal performance decrements with SCL compared to spectacles. PMID- 1594195 TI - Effect of contact lens correction of sine wave contrast sensitivity in keratoconus patients after penetrating keratoplasty. AB - Contrast sensitivity testing reveals visual deficits not detected by standard acuity tests, providing a more sensitive measure of visual performance. Sine wave contrast sensitivity functions were examined for spectacle and contract lens correction of keratoconic eyes after penetrating keratoplasty (PKP). Contrast sensitivity was significantly higher for middle and high spatial frequencies with a rigid gas permeable contact lens than with glasses, even when Snellen acuity was identical for both forms of correction. Contrast performance correlated with subjective assessments of vision quality. This may be related to the quality of the keratometry mire images and suggests that mild irregularities in graft contour may be affecting contrast sensitivity. When considering the options for optical correction of grafted eyes, an evaluation of contrast sensitivity may help determine whether contact lens correction would optimize visual performance. PMID- 1594196 TI - Effects of rigid gas permeable contact lens solutions on the human corneal epithelium. AB - In this investigation, the effects of three rigid gas permeable (RGP) contact lens wetting and soaking solutions, Boston Advance Conditioning Solution, Boston Conditioning Solution, and Allergan Wet-N-Soak Plus, were tested on the human corneal epithelium. Thirty subjects participated in three experimental sessions, during which one eye received three drops of one of these RGP solutions, while the other eye served as a control. After 10 and 30 min, corneal staining was graded in 5 areas and the eyes were photographed for a digitized analysis of staining. Our results indicate that corneas exposed to Boston Advance Conditioning Solution demonstrated significantly more fluorescein staining than control eyes at both 10 and 30 min by both methods of analysis, whereas corneas treated with the other two solutions were not significantly different from controls. The increased corneal staining noted with Boston Advance Conditioning Solution may be caused by the presence and concentration of the preservative, 0.0015% polyaminopropyl biguanide. An unforeseen result of this experiment was the relatively large number of subjects exposed to Boston Conditioning Solution and Allergan Wet-N-Soak Plus who had more corneal staining in the control eye. This may suggest that the two RGP solutions served as a barrier to fluorescein, protecting the epithelial cells from staining. PMID- 1594197 TI - Conjunctival flora in extended wear of rigid gas permeable contact lenses. AB - A longitudinal study was performed to examine the effect of rigid gas permeable (RGP) contact lenses (Boston Equalens II and Quantum II) on the conjunctival flora of 45 young healthy subjects. Microbial flora were determined before delivery of lenses. Subjects wore lenses on an extended wear basis, removing them every 7 days for cleaning and disinfection. Cultures were repeated after 2 months of lens wear and the microbial flora were found to be significantly altered compared to the prelens wear results (0.05 greater than p greater than 0.02). Changes to conjunctival flora included an increase in the number of eyes from which potentially pathogenic microorganisms were isolated, an increase in the number of eyes that were culture-negative, and a decrease in the number of eyes harboring only normal conjunctival flora. The increase in potentially pathogenic flora was not specific for Gram-negative bacteria, which are most often associated with infectious keratitis during contact lens wear. PMID- 1594198 TI - Position of the fovea centralis with respect to the optic nerve head. AB - Examination of the ocular fundus via indirect ophthalmoscopy gives the clinician an impression of foveal position relative to the nerve head. In some patients, the fovea appears to be in an unusual position (i.e., ectopic): it may appear to be higher or lower than expected, or closer to or farther from the nerve head. There is little published quantitative information on this subject. The purpose of this study was to examine foveal position in a group of normal adult eyes, so that clinicians and other researchers will be able to determine on a more objective basis whether or not a given patient shows foveal ectopia. Using ocular fundus photographs for 446 normal adult eyes, we found the foveal center to be, on average, 6.11 degrees +/- 3.32 degrees below a horizontal line bisecting the nerve head. For a smaller sample of 66 eyes, we found the average distance between the nerve head and foveal centers to be 4.93 +/- 0.33 mm (right eye) and 4.88 +/- 0.36 mm (left eye). Correlations of these data for right and left eyes are also examined. Nerve head data for the group of 66 right eyes were also analyzed to yield dimensions of a best-fitting ellipse: the mean minor axis was 1.75 +/- 0.2 mm; the mean major axis 1.95 +/- 0.2 mm. Ectopia (heterotopia) of the fovea has been found in association with chorioretinitis, fibrous traction bands, and/or colobomas of the choroid and optic nerve (including anomalous insertion of the optic nerve), microcephalus, and microphthalmia. A number of separate cases with anomalous nerve heads and/or foveal positions are discussed in this paper.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594199 TI - How useful are contrast sensitivity charts in optometric practice? Case reports. AB - There are now a number of commercially available contrast sensitivity (CS) charts for clinical use. Although a great deal has been written about CS, there is little information regarding its usefulness in optometric practice. In this study 3 commercially available charts (the Vistech system, Pelli-Robson, and Cambridge charts) were used by 6 optometrists in clinical practice over a 14-month period. This report includes a review of the research literature on clinical CS testing, and contains case records from the in-practice study which indicate situations in which the measurement of CS proved useful. PMID- 1594200 TI - Treatment options in intermittent exotropia: a critical appraisal. AB - Clinical opinions regarding treatment of intermittent exotropia (IXT) vary widely and there is controversy as to which treatment modality is most successful. This paper reviews the clinical literature related to five different treatment modalities used for IXT: overminus lens therapy, prism therapy, occlusion therapy, extraocular muscle surgery, and orthoptic vision therapy. Based upon review of 59 studies of treatment of IXT, and using each author's stated criteria for success, the following pooled success rates were revealed: over-minus lens therapy (N = 215), 28%; prism therapy (N = 201), 28%; occlusion therapy (N = 170), 37%; extraocular muscle surgery (N = 2530), 46%; and orthoptic vision therapy (N = 740), 59%. Success rates for IXT surgery differed depending upon whether a functional (43%) or cosmetic (61%) criterion was used to evaluate treatment success. These pooled success rates must be viewed carefully because nearly all the studies suffer from serious scientific flaws such as small sample sizes, selection bias, inadequately defined treatments and success criteria, absence of statistical analysis, and results reported in a manner that makes interpretation difficult. These problems indicate the need for a careful, circumscribed, and well controlled clinical trial to study the efficacy of different treatment modalities in remediating IXT. PMID- 1594201 TI - Monocular acuity in the presence and absence of fusion. AB - Because little is known about monocular acuity during binocular fusion, acuity of the right eye was measured in binocularly normal subjects, with the fellow eye open or fully occluded. The target was flashed for 65 ms or presented sinusoidally for 1 s. Subjects had both eyes optimally focused, or the right eye defocused by +3.00 D. Monocular acuities were equivalent during fusion or occlusion when both eyes were optimally focused. Acuity of the defocused eye was reduced when the fellow eye was open compared to when it was occluded. Suppression of the blur, therefore, produced a measurable reduction in recognition thresholds. As monocular acuity was not measurably affected by the fellow eye when each eye was in focus, the finding that monocular vision is improved with the fellow eye occluded should be ascribed to something other than suppression or more sensitive spatial measures of the suppression should be obtained. PMID- 1594202 TI - Retention of central visual field in retinitis pigmentosa. AB - According to Kanski, roughly one in four patients with retinitis pigmentosa retains visual acuity adequate for reading, although the electroretinogram may be extinguished and the visual field constricted to 2 to 3 degrees (whether diameter or radius is not stated). Under the age of 20 years, an acuity as poor as 6/60 is relatively uncommon, whereas over the age of 50 years such an acuity becomes common. Heckenlively comments that by the end of the 4th decade of life, most males with X-linked retinitis pigmentosa have vision reduced to hand motion or light perception. Women tend to be less severely affected than men: in a study by Bird, only 3 of 48 female heterozygotes had an acuity of less than 6/9, whereas only 8 of 28 hemizygous males had an acuity of 6/9 or better. I thought it would be instructive to analyze the visual field data for a female patient who, although she had suffered considerable loss of peripheral vision, is continuing to function visually quite well. PMID- 1594203 TI - Clinical experience in halting myopia. PMID- 1594204 TI - Graves exophthalmos without muscle involvement. PMID- 1594205 TI - Breast cancer commonly metastasizes to the eye. PMID- 1594206 TI - Prospective versus retrospective studies. PMID- 1594207 TI - Outcomes research and its future impact on physician payment reform. PMID- 1594208 TI - Malignant glaucoma after laser iridotomy. AB - Malignant glaucoma was initially reported as developing after surgery for glaucoma. Subsequently, associations with trauma, inflammation, and the use of miotic agents, as well as spontaneous occurrence have been noted. Laser iridotomy has been assumed to avoid the risk of subsequent malignant glaucoma in eyes with angle-closure glaucoma by avoiding surgical incision of the eye. However, the authors report six cases of malignant glaucoma after laser iridotomy. In all but two cases, medical therapy for the malignant glaucoma resulted in deepening of the anterior chamber and normalization of the intraocular pressure. Malignant glaucoma recurred in five of the patients, and two patients had malignant glaucoma in the fellow eye. PMID- 1594209 TI - Neodymium:YAG laser iridotomy in the initial management of phacomorphic glaucoma. AB - Acute angle-closure glaucoma can be triggered by a mature or intumescent cataract, and occurs in eyes with open angles, as well as in those with narrow, occludable angles. This is encountered more in developing countries, where patients present late. They tend to wait until the cataract becomes mature, because it is common belief among these patients that cataracts should not be operated on until vision drops to the level of hand movements or light perception. The authors reviewed the charts of 10 patients who were treated for phacomorphic glaucoma, by first undergoing neodymium:YAG (Nd:YAG) laser iridotomy. In all patients, the acute angle-closure glaucoma attack could be reversed or prevented by the iridotomy, before subsequent cataract extraction. The value of Nd:YAG laser iridotomy in the initial management of phacomorphic glaucoma is discussed. PMID- 1594210 TI - Aqueous shunts. Molteno versus Schocket. AB - The authors conducted a multicenter, randomized, controlled trial to test whether the Schocket shunt with a larger shunt reservoir surface area would provide a lower final intraocular pressure than the double-plate Molteno implant. However, the Molteno implant produced a statistically lower intraocular pressure at 6 months compared with the Schocket shunt. Postoperative visual acuity, glaucoma medications, and complications were not statistically different. PMID- 1594211 TI - Clinical experience with the single-plate Molteno implant in complicated glaucomas. Update of a pilot study. AB - Ninety-six patients who had undergone single-plate Molteno implantation for glaucomas with poor surgical prognoses were re-evaluated for long-term results. Control of intraocular pressure was achieved with one single-plate implant to a level less than 22 mmHg (but greater than 5 mmHg) without reoperation or devastating complications in 46% of the aphakic/pseudophakic eyes, 25% of eyes after failed filters, 25% of eyes with neovascular glaucomas, and 26% of eyes in patients younger than 13 years of age (life-table analysis at 5 years). Five-year success rates improved to 53%, 71%, 40%, and 56%, respectively, when data from second plates were included. Visual acuities improved or remained the same after one or two plates were implanted in 47% of aphakic/pseudophakic eyes, 17% of eyes after failed filters, 65% of eyes with neovascular glaucomas, and 63% of eyes in patients younger than 13 years of age on whom Snellen acuity was available. The most frequent overall complications after implantation of one or two plates included: corneal edema (19%), corneal graft decompensation (13%), and cornea tube touch, retinal detachment, and cataract (8% each). PMID- 1594212 TI - Pneumotonometry using sterile single-use tonometer covers. AB - Current methods for cleaning pneumotonometer tips include soaking the removable tip in various chemical agents. Disadvantages of this technique include the potential for incomplete disinfection, corneal contact with cleaning solutions, tip damage or loss, and soaking time. The authors studied the use of an available, disposable latex cover placed over the pneumotonometer tip for measuring intraocular pressure (IOP) in 46 eyes with normal corneas from a glaucoma screening clinic and 141 eyes with normal and abnormal corneas from a cornea and external disease clinic. The mean absolute IOP difference comparing with and without the tonometer cover was 1.6 mmHg for the glaucoma screening patients and 1.8 mmHg for the cornea clinic patients. A tonographic-like effect due to repeated tonometry also was shown. An additional study measuring a series of known IOP values in a cadaver eye showed no significant difference between uncovered and covered readings. These data suggest that placement of a disposable, latex cover over the pneumotonometer tip enables accurate IOP measurements and is a sanitary and convenient alternative method to repeated chemical disinfection. PMID- 1594213 TI - Role of the temporal cilioretinal artery in retaining central visual field in open-angle glaucoma. AB - The authors reviewed the optic disc photographs of 34 eyes with high-pressure open-angle glaucoma with advanced visual field loss. Thirteen eyes (38%) had one or two temporal cilioretinal arteries, and 21 eyes (62%) had no temporal cilioretinal artery. All 13 eyes with a temporal cilioretinal artery retained central visual field and had visual acuity of 20/40 or better. In the 21 eyes without a temporal cilioretinal artery, 8 eyes lost central visual field and 12 eyes had a visual acuity of less than 20/40, while 13 eyes retained central visual field and 9 eyes had a visual acuity of 20/40 or better. Significant differences were obtained when eyes with and without cilioretinal arteries were compared for retention of visual field (P less than 0.02) and visual acuity (P less than 0.01). The presence of a temporal cilioretinal artery may provide more circulation to the temporal rim of the optic disc and aid in retaining central field and visual acuity in advanced open-angle glaucoma. PMID- 1594214 TI - High-pass resolution perimetry in neuro-ophthalmology. Clinical impressions. AB - High-pass resolution perimetry is a new technique for visual field testing that determines extrafoveal resolution thresholds. The authors used this method in a neuro-ophthalmology clinic and compared it with other visual field tests. The main advantages of the technique were the short test time and the strong preference by patients for this technique over conventional automated perimetry. The sensitivity and specificity of the test seemed to be as good as or better than conventional perimetry. A minor disadvantage was its slightly less precise spatial definition of field defects. In this report, the authors present their experiences with this new perimetric technique. PMID- 1594215 TI - Pseudotumor cerebri from cranial venous obstruction. AB - Dural sinus hypertension from cerebral venous outflow impairment is a cause of pseudotumor cerebri. The authors documented six such patients: two with unilateral neck dissection, one with surgical ligation of the dominant sigmoid sinus, two with thrombosed central intravenous catheterization, and one with dural sinus thrombosis. The site of cerebral venous outflow obstruction was variable and identified in three patients with computed tomography, conventional magnetic resonance imaging, magnetic resonance angiography, and/or angiography. Magnetic resonance angiography used in two patients characterized the venous flow pattern and identified the site of obstruction, confirming magnetic resonance angiography as an effective noninvasive blood flow technique in diagnosing and following these patients. Three patients were treated successfully with medical therapy and one patient with optic nerve fenestration. The two patients with thrombosed central venous catheters had serious systemic illnesses and suffered permanent visual loss. PMID- 1594216 TI - Enhancement and demyelination of the intraorbital optic nerve. Fat suppression magnetic resonance imaging. AB - Conventional spin-echo magnetic resonance imaging (MRI) of intraorbital optic neuritis is hampered by the adjacent high signal and chemical shift artifact of orbital fat. Frequency-selective saturation pulse MRI reduces these problems and was used to determine its utility in evaluation of intraorbital optic neuritis. Eight consecutive patients with optic neuritis underwent MRI within 1 week of the onset of visual loss. Conventional MRI with T1, proton density, and T2 weighting and frequency-selective saturation pulse MRI with T1, proton density, and T2 weighting were performed. After administration of intravenous gadopentetate dimeglumine, T1-weighted conventional and frequency-selective saturation pulse MRI were performed. Frequency-selective saturation pulse MRI showed gadopentetate dimeglumine enhancement in the intraorbital optic nerve in 7 patients and the intracranial optic nerve in 3 patients. Conventional MRI failed to show optic nerve gadopentetate dimeglumine enhancement in patients with intraorbital lesions, but did show intracranial lesions. Frequency-selective saturation pulse MRI showed bilateral optic nerve enhancement in 3 patients with unilateral visual signs and symptoms. Proton density and T2-weighted conventional MRI of the brain showed no convincing signal aberrations in the optic nerves. In the MRI evaluation of intraorbital optic neuritis: (1) frequency-selective saturation pulse fat suppression MRI is superior to T1-weighted conventional MRI in the detection of gadopentetate dimeglumine enhancement; (2) frequency-selective saturation pulse proton density and T2-weighted MRI is superior to proton density and T2-weighted conventional MRI; (3) frequency-selective saturation pulse MRI showed gadopentetate dimeglumine enhancement as well as proton density/T2 weighted signal aberration in exactly the same portion of the intraorbital optic nerve. PMID- 1594217 TI - Intraorbital optic nerve and experimental optic neuritis. Correlation of fat suppression magnetic resonance imaging and electron microscopy. AB - To provide magnetic resonance imaging (MRI)-ultrastructural correlations of demyelinating lesions of the intraorbital optic nerve, the authors performed gadolinium-enhanced/T2-weighted fat-suppressed MRI and transmission electron microscopy of the optic nerves of animals with experimental allergic encephalomyelitis. Gadolinium enhancement of the optic nerve adjacent to the globe was seen on fat-suppressed T1-weighted MRI as early as 3 days after antigenic sensitization, increased in severity involving longer segments of nerve at 10 to 14 days, and persisted at 30 days. Gadolinium enhancement preceded T2 weighted signal aberrations. Ultrastructural evaluation of the intraorbital nerve revealed: (1) expansion of the extracellular space and inflammatory infiltrate that correlated with the intensity of gadolinium enhancement; (2) the degree of demyelination correlated with T2-weighted signal aberrations; (3) as deduced from gadolinium enhancement and T2 signal aberrations, breakdown of the blood-brain barrier preceded widespread demyelination; (4) lesions appeared to start at the optic nerve insertion into the globe and then progress toward the orbital apex. PMID- 1594218 TI - Incidence of vitreous loss among third-year residents performing phacoemulsification. AB - The incidence of vitreous loss among third-year residents learning phacoemulsification was retrospectively evaluated. One hundred thirty-six cases of phacoemulsification were performed by six different third-year residents with the same attending physician supervising all cases. The incidence of vitreous loss was 14.7%. This study demonstrates that the rate of vitreous loss among residents learning phacoemulsification is higher than the reported incidence of vitreous loss for residents learning planned extracapsular cataract surgery with expression of the lens nucleus. PMID- 1594219 TI - Photic maculopathy after extracapsular cataract surgery. A prospective study. AB - Photic retinal injuries have been described after surgical exposure to the intense illumination systems of operating microscopes. The overall incidence of such injuries has been postulated at less than 10%. The authors prospectively studied 43 consecutive patients to determine the incidence of photic macular injuries during cataract surgery. Patients underwent complete ophthalmic examinations, fundus photography, and oral fluorography before and after surgery. Photic macular injuries developed in 12 of 43 eyes (28%) as a result of intraocular surgery. This incidence is much higher than previous estimates. The association with possible risk factors, cystoid macular edema, and the effect of these injuries on final visual acuity are discussed. PMID- 1594220 TI - Altitude retinopathy on Mount Everest, 1989. AB - The authors studied prospectively the incidence of and risk factors for high altitude retinal hemorrhages among 14 members of the 1989 American Everest Expedition. All subjects had comprehensive eye examinations and fundus photography performed at sea level before the expedition and again at the Mt. Everest Base Camp after 6 weeks of exposure to altitudes between 5300 and 8200 meters. Asymptomatic intraretinal hemorrhages were found in five eyes of four climbers. An additional eye of one of these climbers had a central retinal vein occlusion with vitreous hemorrhage, which reduced visual acuity to counting fingers. Higher baseline intraocular pressure and use of nonsteroidal anti inflammatory drugs were found to be significant risk factors for development of altitude retinopathy. PMID- 1594221 TI - Affected females in X-linked congenital stationary night blindness. AB - Most heterozygous (carrier) females in families with X-linked congenital stationary night blindness are asymptomatic. Several anecdotal cases of manifesting females in X-linked congenital stationary night blindness have been reported, but few clinical details are available. The authors report clinical, electroretinographic, and dark adaptation studies of four affected females from a five-generation family with X-linked congenital stationary night blindness. Each of the manifesting females was the daughter of a different, asymptomatic, carrier mother. None of the 14 daughters of the 9 affected males showed signs or symptoms of congenital stationary night blindness. Uneven X-chromosomal lyonization is the most likely reason for these females manifesting this X-linked disorder. PMID- 1594222 TI - Vitrectomy for diabetic macular traction and edema associated with posterior hyaloidal traction. AB - Pars plana vitrectomy with separation of the posterior hyaloid was performed in 10 eyes with diabetic macular edema and traction associated with a thickened and taut premacular posterior hyaloid. Nine of the 10 eyes had previous macular photocoagulation. Preoperative fluorescein angiography showed a deep and diffuse pattern of leakage in the macula. Intraoperatively, the attached and thickened posterior hyaloid was lifted and separated from the retina. Postoperatively, vision improved in nine eyes. The macular traction and edema resolved in eight eyes and decreased in two. Complications included a vitreous hemorrhage, a rhegmatogenous retinal detachment, cataract formation, and a mild epimacular membrane, each occurring in one eye. Vitreous surgery can improve the visual prognosis of some eyes with diabetic macular traction and edema associated with a thickened and taut posterior hyaloid. PMID- 1594223 TI - Intraocular recurrence of uveal melanoma after proton beam irradiation. AB - The authors evaluated tumor recurrence as an end point in 1077 uveal melanoma patients treated by proton beam irradiation between 1975 and 1987, with a mean follow-up of 4.0 years. Twenty tumors (1.9%) exhibited definitive growth between 4 months and 66 months after irradiation (median, 19 months): 10 were marginal recurrences, 5 were ring melanomas, 3 were uncontrolled tumors, and 2 were extrascleral extensions. Ten of these eyes were enucleated without further intervention, 2 patients died of metastases soon after the growth was detected, and 8 patients had further conservative therapy. In 5 other patients, tumor growth was suspected but unconfirmed and the eye was enucleated elsewhere; the 5 year probability of local tumor control based on 25 recurrences was 97% +/- 1%. There was a nonsignificant increase in the rate of metastases among patients with documented tumor recurrence (adjusted relative risk, 1.5; 95% confidence interval, 0.66 to 3.4). Results suggest that recurrence of uveal melanomas treated by proton beam therapy is uncommon, but that treatment failure may increase risk of death from metastasis. PMID- 1594224 TI - Long-term results of iodine 125 irradiation of uveal melanoma. AB - The authors report on 64 of the first 65 patients treated with iodine 125. The mean follow-up was 64.9 months. After treatment, 29 patients (45.3%) retained visual acuity of 20/100 or better, and 18 patients (28.1%) retained visual acuity within two lines of visual acuity before irradiation. Eleven patients (17.2%) died of metastasis, and 5 patients (7.8%) had local recurrence. Cataract developed in 29 (45.3%) patients; keratitis developed in only 2 (3.1%) patients, and dry eye developed in none. Neovascular glaucoma developed in 7 (10.9%) patients, and 15 (23.4%) patients had radiation retinopathy. Eleven patients (17.2%) required enucleation for either tumor growth or neovascular glaucoma. These results show the increasing number of radiation complications seen with long-term observation and the frequently seen adverse visual outcome. PMID- 1594225 TI - Factors associated with high postoperative myopia after penetrating keratoplasties in infants. AB - Sixteen penetrating keratoplasties performed in patients younger than 2 years of age were reviewed to determine which factors were associated with high postoperative refractive errors. When tissue from donors younger than 2 years was used, the mean postoperative spherical equivalent was -13.7 diopters, compared with +2.0 diopters when tissue from donors older than 2 years was used (P = 0.001). Analysis of variance suggests that the use of a 0.5-mm oversized transplant, as opposed to a 0- to 0.3-mm oversized transplant, contributed to the production of high myopia when tissue from donors younger than 2 years was used (P = 0.009). The high myopia appears to have resulted from steep transplant curvatures. Based on these results, we recommend against the combined use of corneal transplant tissue from very young donors and 0.5-mm oversized transplants for infant penetrating keratoplasties. PMID- 1594226 TI - Comparison of techniques for culturing corneal ulcers. AB - All consecutive cases of presumed microbial keratitis were cultured with both a platinum spatula and calcium alginate swab moistened with trypticase soy broth. Ten (77%) of the 13 culture-proven ulcers in this series showed a greater number of colonies and more confluent growth on the agar plates inoculated with a moistened swab compared with a much lower yield obtained using a platinum spatula. All culture-positive bacterial ulcers showed growth when cultured with a swab. Two ulcers that were partially treated before culturing yielded very light growth from those rows inoculated with a swab and no growth from those rows inoculated with a spatula. Two ulcers showed equal growth between the two methods. One ulcer (Actinomycetes-Streptomyces/Nocardia) had greater growth obtained with a spatula compared with a swab. This series demonstrated a significantly greater retrieval of organisms from bacterial keratitis when a calcium alginate swab moistened with trypticase soy broth was used to rub the ulcer and directly inoculate the solid agar media. The single case of filamentous bacteria suggests that a spatula may yield better organism retrieval from ulcers caused by filamentous organisms. PMID- 1594227 TI - Clinical follow-up of 193-nm ArF excimer laser photokeratectomy. AB - The excimer laser has been undergoing rapid development for clinical use since the early 1980s. The authors report 2-year follow-up results from studies in 31 eyes (15 women and 14 men) to evaluate the excimer laser in performing photokeratectomy. Patients were divided into two groups: 27 eyes (group 1) underwent phototherapeutic keratectomy, and 4 eyes (group 2) underwent photorefractive keratectomy. Visual function improved in 21 of 27 eyes in group 1 and in 2 of 4 eyes in group 2. Complications were minimal and manageable. The authors describe a procedure to minimize induced hyperopia in phototherapeutic keratectomy patients, and, although not statistically significant, less induced hyperopia was noted in these patients. Photokeratectomy may be an alternative to penetrating or lamellar keratoplasty and more invasive refractive procedures, but the long-term effects must be carefully observed. PMID- 1594228 TI - Cryptococcosis of the anterior segment in acquired immune deficiency syndrome. AB - Cryptococcosis is a rare form of human ocular infection, usually occurring in immunocompromised patients. Unilateral or bilateral posterior segment involvement is the rule. The authors describe a unique case of intraocular cryptococcosis presenting as an iris inflammatory mass in a patient with acquired immune deficiency syndrome. Diagnosis was established by anterior chamber paracentesis and confirmed by histopathologic examination of the enucleated eye. PMID- 1594229 TI - Secondary localized amyloidosis in interstitial keratitis. Clinicopathologic findings. AB - Cases of secondary localized corneal amyloidosis have been described in various corneal and ocular inflammations but are believed to occur uncommonly. The authors examined histopathologic specimens from 33 consecutive patients with interstitial keratitis who underwent penetrating keratoplasty for visual rehabilitation. In 11 cases (33%), multiple fusiform deposits of amyloid were identified and confirmed in middle and deep corneal stroma using histochemical staining. Characteristic electron microscopic findings were present in two cases. These results indicate that secondary localized corneal amyloidosis occurs frequently in interstitial keratitis and displays a distinct pattern of deposition. PMID- 1594230 TI - [Closed treatment of fractures of the humeral head. Indications, technique, limits]. AB - Beginning with the specific mechanism of injury and characteristic physical and radiographic signs, the different forms of conservative treatment of fractures of the upper humerus are presented. As a result of biomechanical principles, the forces that generate the fracture cause dislocations of the fragments, and these dislocations follow basic rules. A fracture is considered dislocated if any of the fragments are displaced over 1 cm or if the angulation is more than 45 degrees. In dislocated fractures of the proximal humerus, reduction is indicated. The technique is presented in detail for the different types of fractures. Minimally displaced fractures or those that may be reduced by closed methods and do not redislocate are usually managed by conservative treatment. The affected shoulder is immobilized as a rule in a Gilchrist sling for 1-2 weeks. Functional exercises begin as soon as false motion of the fracture can be excluded by careful examination. In order to achieve optimal functional recovery, the exercises should be continued for longer than the bone union; that can be expected at 6-8 weeks. The special features and limitations of conservative treatment are discussed in relation to the different types of fractures. PMID- 1594231 TI - [Intramedullary nailing of unstable proximal humeral fractures]. AB - Unstable subcapital fractures and dislocation fractures of the humerus can usually be set by closed reduction. Stabilization of these fractures by intramedullary pins is a method which avoids damage to the soft tissues around the shoulder. Since 1985, elastic steel pins with special features have been in use. The last 20 mm of the tip of the pins is angulated at 15 degrees, and the distal end is curved in a special way for the last 20 mm. According to our experience, the results after using this method in the treatment of unstable fractures of the surgical neck (ASIF type A II/2) and dislocation fractures (ASIF type A III/2) are fair to very good. For unstable fractures (ASIF type C I/2) and other dislocation fractures (ASIF type C III/2), the method is only suitable if good reduction is possible. Between the end of February 1985 and the end of December 1990, 101 fractures of the proximal end of the humerus were treated by closed reduction and fixation with intramedullary pins. Following fractures in the anatomical neck, aseptic necrosis of the fragment of the head leads to unfavorable results. In two patients, pseudarthrosis with poor function developed. Disturbance of wound healing, postoperative hematoma, infection, myositis ossificans, or Sudeck's desease have not been observed. PMID- 1594232 TI - [Osteosynthesis in dislocated fractures of the humerus head]. AB - The operative treatment of displaced fractures of the proximal humerus has changed during the last few years. Minimal osteosynthesis takes into consideration to a great extent the biological aspects of these fractures and provides sufficient stability for early functional therapy. Neer's classification has proved very useful for both the indication for and the choice of an operative procedure. The high necrosis rate of the operatively stabilized humeral head has considerably influenced the operative strategy. This is shown in two separately controlled patient groups. From 1970 to 1980, 65 patients and from 1983 to 1987, 30 patients with displaced fractures of the proximal humerus were treated operatively. Within the first group, in more than half the cases a T-plate osteosynthesis was performed, a minimal osteosynthesis being performed in only 1 out of 5 patients. In the second group, we exclusively performed minimal osteosynthesis. More favourable results were achieved in fractures with two or three fragments, in younger patients and in isolated shoulder injuries than with four-fragment fractures or luxated fractures, in older and in polytraumatized patients. Using minimal osteosynthesis instead of plate osteosynthesis in four fragment fractures, functional results were achieved which, in 75%, were satisfactory or better. The necrosis rate of the humeral head also declined. We conclude that head-preserving methods seem advisable in these severe forms of humeral fractures. PMID- 1594233 TI - [Dislocation fractures of the shoulder. Special status and therapeutic concepts]. AB - Shoulder dislocations associated with a displaced fracture of the humeral head or glenoid require different treatment than shoulder dislocations without fracture. If the humeral head is fractured, two possible complications must be considered:impairment of the subacromial gliding mechanism and insufficient blood supply to the humeral head. In glenoid fractures, instability may be induced. The degree of instability depends on the size of the fragment. In fractures of the humeral head, in particular of the greater tuberosity, we differentiate between the so-called en bloc fracture and the so-called supra-spinatus avulsion fracture. In "en bloc" fractures, one has to be aware that displacement of the fragment can occur not only in the superior direction but in the posterior direction as well. Posterior displacement is displayed radiologically by the "tangential" view. Both the duration of pain and range of motion depend on the amount of displacement of the fragment. Displacement exceeding 3 min in one direction should be reduced surgically in the active patient. For operative treatment of a displaced "en bloc" fracture, we recommend closed reduction and percutaneous screw fixation performed under regional anesthesia. "Supraspinatus avulsion fractures" ought to be treated like rotator cuff tears because there is no possibility of the small fragments healing due to their placement on the joint cartilage. In fracture dislocations, the blood supply of the humeral head is seriously jeopardized if the fracture is situated in the anatomical neck, whereas this is not the case in a fracture of the surgical neck. The number of displaced fragments allows a prediction concerning the survival of the articular segment of the humeral head.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594234 TI - [Primary humerus head replacement in dislocated proximal humeral fracture. Indications, technique, results]. AB - Displaced three- and four-part fractures of the humeral head detached from their blood supply are at high risk for a poor functional outcome after internal fixation. Primary prosthetic replacement can restore the pretraumatic anatomy, and early function is possible. Head replacement within 2 weeks after trauma, reapproximation of the tuberosities, and reconstruction of the rotator cuff tear establishes early stability and good functional results in up to 80%. PMID- 1594235 TI - [Corrective interventions subsequent to humeral head fractures]. AB - The complications of old fractures of the proximal humeral head and fracture dislocations are nonunion, malunion, osteonecrosis, early traumatic arthritis, chronic dislocation and instability with subluxation. We reviewed a consecutive series of 34 shoulders that were treated between 1986 and 1990. We performed 7 hemiarthroplasties and 11 total shoulder arthroplasties (Neer type) in 17 patients (group I). Group II consisted of 12 osteotomies, 3 internal fixations for nonunion (AO technique), and 1 shoulder arthrodesis. The average follow-up was 27 months (group I) and 26 months (group II), respectively. The results were: good in 32%, fair in 50%, and poor in 18% in group I; excellent in 6%, good in 62%, and fair in 32% in group II. The results indicate that varus/valgus osteotomies and derotation osteotomies should be considered as an alternative procedure prior to arthroplasties before traumatic arthritis has developed. Internal fixation for nonunion (AO technique) is a replacement for hemiarthroplasty. PMID- 1594236 TI - [Scapula fractures--classification and differential therapy]. AB - The classification of fractures of the scapula (type A: body and process fractures; type B: neck fractures; type C: glenoid fractures) is shown, and the indications for conservative and operative treatment are described, as are the surgical approaches and operative techniques. In our hospital, 93 patients with 153 fractures of the scapula type A, B or C (ratio 1.6:1) were treated. This ratio was 1.7:1 in patients treated by operation. The indication for operation was usually glenoid fractures with accessory process fractures. PMID- 1594237 TI - [Special status of lateral clavicular fracture]. AB - Fractures of the lateral clavicle have different biomechanical conditions compared with fractures of the medial and central third; they therefore demand different therapy. Some 237 patients with fractures of the clavicle were followed, of which 75 (33%) were located in the lateral third of the clavicle. At the 5-year follow-up after exclusively conservative treatment, good results were found for Neer types I and III and 3 Jager/Breitner type IIb fractures, while 4 out of 13 Jager/Breitner type II a fractures ended in pseudarthroses (31%). Conservative treatment is recommended for Neer types I and III, as well as for the more stable Jager/Breitner type II b and old II a fractures. Therefore, a new bandage is presented. It prevents the posterior and upward dislocation of the proximal fragment by vertical compression and rotation of the distal fragment by fixation of the arm. Open reduction and internal fixation by preferably extraarticular implants is recommended for unstable and dislocated Jager/Breitner type II a fractures. For fractures of the lateral clavicle, good results can be achieved when the instability is recognized and adequately treated. PMID- 1594238 TI - [Classification of fractures and problems in proximal humeral fractures]. AB - Complex fractures of the proximal humerus may be difficult to assess and treat. Open or closed reduction and fixation may lead to malunion, nonunion, and/or avascular necrosis. Conversely, hemiarthroplasty also does not always result in satisfactory functional results. Various classifications have been established to compare the results of treatment and assist in decision making. The most commonly used classifications are those of Neer and the AO/ASIF group both of which appear to overestimate the relevance of avascular necrosis and underestimate the relevance of malunion. Because of the inter- and intraobserver variability in classifying these fractures, there is the potential for a wide variety of treatment recommendations, and predicting the prognosis becomes less accurate. Further work should be done in standardizing the classifications of proximal humerus fractures and defining the necessary X-ray projections. PMID- 1594239 TI - Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus. AB - Inactivation of the DCC gene on chromosome 18 owing to loss of heterozygosity is a common finding in colorectal cancer. Because both ovarian and colon cancer are features of Lynch syndrome II, which has been provisionally mapped to chromosome 18, we hypothesized that loss of heterozygosity at the DCC locus may also occur in ovarian neoplasia. Fifty-two sporadic ovarian adenocarcinoma tumours were analysed by Southern blotting for loss of heterozygosity (LOH) at six chromosome 18 loci. Overall, tumours from 31 patients (60%) showed allelic loss at one or more of these loci. A similarly high level of LOH, 66%, was found at D17S5 (17p13.3). In contrast, moderate levels of LOH, of 31%, 39% and 33%, were found at MYCL1 (1p32), D1S57 (1p) and D14S20 (14q32.33) respectively. However, analysis of partial chromosome deletions in 11 patients indicates that the smallest region of overlap appears to exclude the DCC gene but to be between the D18S5 and D18S11 loci. This suggests that another locus, as well as or apart from DCC, may be involved. PMID- 1594240 TI - cdc2-like kinase is associated with the retinoblastoma protein. AB - The growth-suppressive activity of the retinoblastoma (RB) protein is suggested to be regulated by phosphorylation. In studies on the kinase that phosphorylates the RB proteins, we have previously found that RB proteins can be phosphorylated by purified cdc2 kinase. In this study, we noted that RB proteins immunoprecipitated from human cell lysates are weakly phosphorylated in the absence of purified cdc2 kinase. Immunoblot analysis showed the presence of p34cdc2 in the immunoprecipitates with anti-RB monoclonal antibody. In addition, the coprecipitated kinase was found to have the same substrate specificity as cdc2 kinase. The associated kinase activity was particularly high in cells arrested in G1/S and S phase by aphidicolin. Furthermore, RB proteins were shown to be phosphorylated in nuclear extracts by some endogenous cdc2-like kinase(s). These results suggest that cdc2-like kinase is the main kinase for phosphorylation of RB proteins in vivo. PMID- 1594241 TI - Alternative splicing of PML transcripts predicts coexpression of several carboxy terminally different protein isoforms. AB - The acute promyelocytic leukaemia (APL)-specific chromosome 15;17 translocation leads to the fusion of a newly identified putative transcription factor, PML, and the retinoic acid receptor alpha. We have characterized the structure of the PML genomic locus and preliminarily characterized its expression pattern. The PML locus spans a minimum of 35 kb and is subdivided into nine exons. The putative PML DNA binding site is encoded by exons 2 and 3. We isolated a large number of alternatively spliced PML transcripts that encode numerous PML isoforms. Two groups of isoforms were identified that differed either in their C-terminal region or in the length of their central region, but retained the putative DNA binding and dimerization domains. RNAase protection experiments revealed that the different PML isoforms are equally expressed in established cell lines of different histological origin. PMID- 1594242 TI - An antisense interferon-beta RNA abolishes repression of c-fos gene expression. AB - To determine the cellular functions which are modified when interferon-beta (IFN beta) gene expression is inhibited, a plasmid allowing the constitutive expression of RNA complementary to IFN-beta mRNA was constructed and stably introduced into L929 cells. Some of the selected clones expressing this antisense IFN-beta mRNA, named L-ASI, were unable to produce IFN-beta and lost the ability to arrest in the G0 phase of the cell cycle. Indeed, the usual transrepression of the c-fos gene observed in quiescent cells was blocked in IFN-beta antisense L ASI clones and the c-fos gene was permanently stimulated. This overexpression of c-fos was not modified in response to protein kinase C agonists such as phorbol esters, but increased in response to the adenylate cyclase activator forskolin. In addition, the ability to induce major histocompatibility class I genes following recombinant IFN-beta treatment was impaired in antisense IFN-beta L-ASI clones, suggesting an important alteration of this cell with regard to the interferon system. Unexpectedly, the tumorigenicity of the clones was significantly diminished. We postulate that IFN-beta antisense RNA blocks the repression of the c-fos gene and thus prevents the arrest of cells in the G0 phase of the cycle. PMID- 1594243 TI - Transformation by Jun: requirement for leucine zipper, basic region and transactivation domain and enhancement by Fos. AB - Mutants in the leucine zipper and basic regions of mouse c-jun were tested for transformation in chicken embryo fibroblast cultures. Reduction or elimination of the ability of Jun to dimerize or to bind to DNA severely decreased transformation. A chicken v-jun gene from which the major transactivation domain was deleted also failed to transform. We conclude that an intact leucine zipper, basic region and transactivation domain are required for Jun-induced oncogenic transformation. Coexpression of chicken c-Fos increased formation of transformed foci by Jun proteins of moderate to low oncogenic potency but had no effect on highly transforming Jun. Chicken c-Fos could also transform chicken embryo fibroblasts on its own, albeit after prolonged culture and at a low efficiency. PMID- 1594244 TI - Transfection of activated c-H-rasEJ/pSV2neo or pSV2neo genes into rat mammary cells: rapid stimulation of clonal diversification of spontaneous metastatic and cell-surface properties. AB - We examined whether the conversion of benign rat mammary cells to metastatic cells by transfection of c-H-rasEJ/pSV2neo or control pSV2neo genes results in rapid stimulation of diversification of cellular phenotypes. Transfection of c-H rasEJ into twice-cloned, stable (greater than 1 year) rat mammary MTC.4 cells, followed quickly by cell cloning, revealed differences in transfected oncogene copy numbers and expression of p21rasEJ. No correlation between c-H-rasEJ copy numbers or the cellular amounts of p21rasEJ or total p21ras and spontaneous metastatic potentials was found. By subcloning transfected cells as soon as possible after gene transfer, we found some rearrangements and amplifications of c-H-rasEJ and heterogeneous spontaneous metastatic potentials. In addition, the expression of the mammary tumor metastasis-associated cell-surface glycoprotein gp580 on untransfected and transfected MTC.4 cells indicated that the cell populations of higher metastatic potential were also more diverse in their cell to-cell antigen expression than untransfected or non-metastatic, transfected MTC.4 cells. In contrast, the expression of a putative metastasis-suppressor gene, nm23, was unchanged after transfection and subcloning. Control pSV2neo transfections or calcium phosphate treatment alone also resulted in the generation of cellular heterogeneity, although at an apparently lower frequency than c-H-rasEJ transfections, suggesting that transfection of activated, dominantly acting oncogenes, or in some cases control genes, can result in destabilization of transfected cells, rapid diversification and generation of heterogeneity in growth rate, spontaneous metastatic potential and antigen expression. PMID- 1594245 TI - Mutations in the rel-homology domain alter the biochemical properties of v-rel and render it transformation defective in chicken embryo fibroblasts. AB - Sequential deletions of approximately 100 base pairs were made in the rel homology domain of the viral rel protein. Each deletion mutant was cloned into a replication-competent viral vector and assayed in chicken embryo fibroblasts (CEFs). The deleted v-rel proteins were analysed for localization, complex formation and ability to induce transformation. In vitro-translated mutant proteins were assayed for binding to a NF-kappa B consensus sequence. All the deletion mutants between nucleotides 37 and 798 in v-rel were transformation defective. Each of the mutants localized predominantly in the cytoplasm, whereas wild-type v-rel localizes predominantly in the nucleus of CEFs. Any disruption of the rel-homology domain reduced binding of the mutant v-rel proteins to the cellular protein, p36, while the requirements for binding to p68c-rel, p115 and p124 appeared to be more complicated. The binding of these three proteins to v rel appeared to be linked and mediated through c-rel, suggesting that v-rel disrupts normal c-rel function. None of the deletion mutants in this region were able to bind to the NF-kappa B site. However, mutants which lie outside the rel homology domain retained the ability to transform CEFs, localize to the nucleus, complex with p36, p115, p124 and p68c-rel and bind to the NK-kappa B site. These results suggest that transformation by v-rel requires an intact rel-homology domain and that the biochemical properties of v-rel are linked and dependent upon higher order protein structure for full function. PMID- 1594246 TI - High frequency of p53 gene alterations associated with protein overexpression in human squamous cell carcinoma of the larynx. AB - A series of 58 primary human squamous cell carcinomas of the larynx (LSCCs) was examined for the expression of the p53 tumor-suppressor gene by a combined immunohistochemical and molecular approach. About 60% of the cases displayed nuclear p53 overexpression as revealed by immunostaining with PAb1801, PAb122 and PAb240 monoclonal antibodies. This phenomenon was associated with the presence of structural and/or transcriptional alterations of the p53 gene. Our results provide evidence that p53 abnormalities constitute the most frequent genetic alteration identified so far in LSCC and indicate that the abnormal accumulation of the protein correlates with the presence of p53-mutated versions. These findings, taken together with the peculiar biochemical properties of p53, support the hypothesis of a possible pathogenetic relationship between smoke carcinogen exposure and p53 inactivation in the development of this tumor type. PMID- 1594247 TI - Deletion mapping of chromosomes 14q and 1p in human neuroblastoma. AB - It has been suggested that loss of heterozygosity (LOH) on the short arm of chromosome 1 is a critical event for the development of neuroblastoma, and we have previously shown frequent LOH on chromosome 14 in neuroblastoma. To pursue these observations, especially to define further the regions which are commonly deleted in the tumor, we examined for allelic losses in 27 cases of neuroblastomas by using a number of polymorphic DNA markers for chromosomes 14q and 1p. LOH was observed in 10 out of the 25 informative cases (40%) on chromosome 14q and in eight out of the 21 informative cases (38%) on 1p. The commonly deleted regions were distal to the D14S13 locus (14q32-qter) on chromosome 14 and distal to the D1S112 locus (1p36.1-pter) on chromosome 1. These results strongly suggest that tumor-suppressor genes important in the pathogenesis of human neuroblastoma are located on the distal part of both chromosomes 14q and 1p. PMID- 1594248 TI - Generation and characterization of transforming variants of the lck tyrosine protein kinase. AB - p56lck, a tyrosine protein kinase of the src family, is overexpressed in two murine thymoma cell lines, LSTRA and Thy19, as a result of the integration of Moloney murine leukemia virus sequences upstream of the lck gene. The majority of the p56lck in these cell lines is translated from a hybrid mRNA comprised of the 5' untranslated region of the murine leukemia virus env mRNA and lck coding sequences. The retroviral promoter giving rise to this transcript has been molecularly cloned. To examine whether overexpression of unmutated p56lck might induce cellular transformation, we constructed a plasmid in which the murine leukemia virus promoter from LSTRA cells directed the expression of p56lck. This construct gave rise to foci when transfected into rat 208F fibroblasts. Cells from many of the foci also grew in soft agar. Tryptic peptide mapping showed that the p56lck in the transformed cells was phosphorylated at Tyr-394, the autophosphorylation site, but not detectably at Tyr-505, an inhibitory site. Because an antiserum made to the carboxy terminus of p56lck could not immunoprecipitate p56lck from these transformed cells, the possibility arose that the proteins expressed in the transformed fibroblasts contained mutations that altered the carboxy terminus of the protein. cDNAs derived from the 3' ends of the lck mRNAs in two of the foci were cloned, and both were found to be derived from an lck gene that was truncated upstream of the codon for Tyr-505 and fused to random sequences derived from other parts of the construct used for transfection. lck therefore resembles several other src family members in that it can be rendered oncogenic by replacement of the region encoding the inhibitory, carboxy-terminal phosphorylation site by random amino acid sequences. PMID- 1594249 TI - Transcriptional activation of the c-myc gene by the c-myb and B-myb gene products. AB - To identify the target genes modulated by the myb gene product (Myb), a co transfection assay with a Myb expression plasmid was performed. Both c-Myb and B Myb, another member of the myb gene family, trans-activated the human c-myc promoter. DNAase I footprint analysis using the bacterially expressed c-Myb, identified multiple c-Myb binding sites in the c-myc promoter region. Deletion analysis of the c-myc promoter suggested that some number of Myb binding sites, not a specific Myb binding site, is important for the c-Myb-induced trans activation of the c-myc promoter. Using the c-myc-chloramphenicol acetyltransferase (CAT) construct as a reporter in a co-transfection assay, the domains of c-Myb required for trans-activation were examined. The functional domains of c-Myb identified using the c-myc promoter were almost the same as those identified previously with the artificial target gene containing Myb binding sites, but unlike the case with the artificial target gene the N-terminal half of the previously identified negative regulatory domains and the C-terminal 136 amino acids were required for the maximal trans-activation of the c-myc promoter. These results indicate that there are some differences in the regulation of Myb-dependent trans-activation in different target genes. PMID- 1594251 TI - Cancer is a political issue. PMID- 1594250 TI - Mapping of MAX to human chromosome 14 and mouse chromosome 12 by in situ hybridization. AB - The protein encoded by the MAX gene is a member of the class of basic region helix-loop-helix-zipper proteins and has been demonstrated to associate with N-, L-, and c-Myc proteins both in vitro and in vivo. Heterodimers formed between c Myc and Max proteins have been shown to possess sequence-specific DNA-binding activity. Here we report the mapping of the MAX gene to a single region on human chromosome 14 (bands q22-q24) and to mouse chromosome 12 (region D). Chromosome abnormalities linked to several neoplasms have been previously associated with this region on human chromosome 14. The mapping results also confirm a region of homology between human chromosome 14q22-24 and mouse chromosome 12 region D. PMID- 1594252 TI - Evaluation of multi-dimensional pain scales. PMID- 1594254 TI - Are persons with migraine characterized by a high degree of ambition, orderliness, and rigidity? AB - Participating in the study were 69 persons with migraine and 69 controls, matched for sex and age, and all being patients of a neurologist. They filled out a questionnaire purporting to measure personality traits regarded as characteristic for the migraine personality type, namely ambition, orderliness, and rigidity. No differences between groups in any of the scales were revealed using t tests, results being far from significant. No support was thus given for the assumption of a typical personality structure of migrainous subjects. This is in accordance with our findings from previous studies with non-clinical samples. PMID- 1594253 TI - Identification of patient, medical and nursing staff attitudes to postoperative opioid analgesia: stage 1 of a longitudinal study of postoperative analgesia. AB - Sixty-one successive patients undergoing routine cholecystectomy together with all the registered nursing staff and junior doctors working on the surgical wards in a major teaching hospital were studied by means of questionnaires. These were designed to identify beliefs and attitudes to postoperative analgesia in the hospital. The survey revealed that there is a continuing prevalence among medical and nursing staff of attitudes and practices likely to contribute to poor postoperative analgesia. Patients had low expectations of pain relief and displayed reluctance to request analgesia. Injections were generally effective when given, but dosing intervals were often too long for good analgesia. With this knowledge it has been possible to devise strategies to counteract those attitudes leading to poor analgesia and these have formed the basis of a new Acute Pain Service. It is intended to repeat this survey at 3 yearly intervals in order to monitor progress. PMID- 1594255 TI - Traditional Chinese acupuncture in tension-type headache: a controlled study. AB - Thirty patients with tension-type headache were randomly chosen to undergo a trial of traditional Chinese acupuncture and sham acupuncture. Five measures were used to assess symptom severity and treatment response: intensity, duration and frequency of headache pain episodes, headache index and analgesic intake. The five measures were assessed during a 4 week baseline period, after 4 and 8 weeks of treatment, and 1, 6 and 12 months thereafter. Before the start of the study, each patient was administered the MMPI. Split-plot ANOVAs showed that, compared to baseline, at 1 month after the end of treatment and for the 12 month follow up, the frequency of headache episodes, analgesic consumption and the headache index (but not the duration or intensity of headache episodes) significantly decreased over time; however, no difference between acupuncture and placebo treatment was found. No single MMPI scale predicted the response to treatment, but the mean MMPI profile of acupuncture non-responders showed the presence of 'Conversion V'. PMID- 1594256 TI - Chronic pain, depression, and the dexamethasone suppression test. AB - In most healthy individuals, dexamethasone suppresses adrenal cortisol production. However, in patients with major depression, non-suppression frequently occurs and thus may be a marker for depression. The purpose of the present study was to examine the relationship of dexamethasone suppression test (DST) non-suppression to clinical variables such as major depression, site and duration of pain, prior surgery, and medication use in 81 chronic pain patients beginning inpatient pain treatment (Inpt. Pain), and 33 medication-restricted outpatients with chronic back pain and depression (Outpt. Back). In the Inpt. Pain group, the specificity of DST non-suppression for depression was 82% and for sensitivity 24%. In the Outpt. Back group, its sensitivity was 18%. Within the diverse inpatient samples, there was 69% non-suppression in patients with headache pain only, compared to 15% in patients with other sites of pain (P less than 0.01), but there was no significant difference in depression rate between these two groups. In the Inpt. Pain group, non-suppressors also had significantly less prior surgery. In the Outpt. Back group, opioid use was significantly higher in non-suppressors (33%) than in suppressors (11%). In chronic pain populations, the DST appears not to be useful clinically for the detection of depression and may be significantly affected by clinical variables other than depression. PMID- 1594257 TI - Patient controlled analgesia for extracorporeal shock wave lithotripsy of gallstones. AB - Sixty patients undergoing shock wave lithotripsy of gallbladder stones (ESWL) were randomly assigned to receive alfentanil either by infusion controlled by the attending anesthesiologist (standard treatment group, n = 31) or by analgesia controlled by the patient (PCA group, n = 29). Patients using PCA were allowed to self-administer 0.25 mg of alfentanil i.v. every minute as required. Data collected during treatment included the total dose of drug required, transcutaneous pCO2 values, verbal pain and sedation scores, visual analogue scale (VAS) patient satisfaction scores, and the incidence of nausea or vomiting. PCA patients used less alfentanil than the standard treatment group (PCA group: 12.8 micrograms/kg; standard treatment group: 44.3 micrograms/kg; mean values, P = 0.0001), tolerated significantly higher pain intensities and self-administered the narcotic only to moderate levels of pain but not to pronounced analgesia. Standard treatment patients reported lower levels of pain, were more sedated (P less than 0.05) and showed significantly higher transcutaneous pCO2 values. There was a trend towards a lower incidence of nausea or vomiting in PCA patients without reaching statistical significance. No significant difference with regard to patient satisfaction with pain relief could be demonstrated. Self-administered alfentanil during ESWL of gallbladder stones provided adequate analgesia with minimal side effects and high patient satisfaction. ESWL may represent a new and useful indication for PCA. PMID- 1594258 TI - Acute and remitting painful diabetic polyneuropathy: a comparison of peripheral nerve fibre pathology. AB - The cause of the neuropathic pain that is experienced by some patients with diabetic neuropathy remains to be established. Early neuropathological reports, based on comparisons between diabetic patients and non-diabetic control subjects, emphasised associations between pathological changes in specific classes of peripheral nerve fibre and the presence of pain. By making comparisons with more appropriate control subjects, namely diabetic patients without neuropathic pain, more recent studies have found that there are few clear morphological correlates for this type of pain. To investigate this further, we have conducted a detailed morphometric study of sural nerve biopsies from six diabetic patients, four with active acute painful neuropathy and two with recent remission from the same condition. Normal values for the neuropathological parameters were obtained from six non-diabetic control subjects. Teased fibre analysis showed that similar axonal and Schwann cell abnormalities were present in both groups of diabetic patients. Electron microscopical studies revealed that evidence of both myelinated and unmyelinated fibre degeneration and regeneration was also present in the nerves of all diabetic patients, irrespective of whether they had pain. Within the constraints of interpreting results from small numbers of patients, our observations suggested that remission from pain might be associated with a less abnormal axon/Schwann cell calibre ratio, more successful myelinated fibre regeneration and less active unmyelinated fibre regeneration. However, the inescapable finding of this study was, in fact, the similarity in the nerve fibre pathology in diabetic patients with active and remitting painful neuropathy. We conclude that the occurrence of nerve fibre degeneration and regeneration is in itself unlikely to be sufficient to account fully for diabetic neuropathic pain. However, it is conceivable that events occurring during certain stages in the pathological cycle of degeneration and regeneration create the necessary circumstances which lead to pain. PMID- 1594259 TI - Do patients with primary fibromyalgia have an altered muscle sympathetic nerve activity? AB - This study was performed to test the existing notion that an increased muscle sympathetic nerve discharge is part of the underlying mechanism for the chronic pain syndrome of primary fibromyalgia. Muscle sympathetic nerve activity was recorded in the peroneal nerve in eight patients with primary fibromyalgia and eight age-matched controls. No difference in baseline sympathetic activity was observed between patients and controls. Furthermore, patients did not show exaggerated sympathetic nerve responses to static handgrip or jaw muscle contractions, postcontraction ischemia or mental stress. Thus the results do not indicate muscle sympathetic nerve overactivity in primary fibromyalgic patients. PMID- 1594260 TI - Lidocaine test in neuralgia. AB - Ten patients with organic nerve injury causing chronic neuropathic pain were tested for the effects of intravenous lidocaine versus saline upon psychophysical somatosensory variables. The variables assessed were the subjective magnitude of pain, area of mechanical hyperalgesia and presence and magnitude of thermal heat/cold hyperalgesia. The study methods applied to evaluate these conditions were the conventional testing of somatosensory submodalities with area mapping and the subjective magnitude estimation of spontaneous pain. It was found that spontaneous pain and mechanical hyperalgesia were consistently improved, transiently, by intravenous administration of lidocaine in all 10 patients; areas of hyperalgesia which extended beyond the territory of the nerve also improved transiently. Spontaneous pain and mechanical hyperalgesia, but not hypoesthesia, were transiently improved by injection of saline in only 1 of the 10 patients. This outcome is probably due to a placebo effect. This improvement is in keeping with the inhibition of anomalous neural impulses which can be generated anywhere along the sensory channels responsible for generating spontaneous pain and hyperalgesia. Thus, intravenous lidocaine is proposed as a diagnostic aid in the examination of patients complaining of complex sensory disorders associated with nerve injury. The transient pain relief may allow a fuller identification of the area of sensory loss. PMID- 1594261 TI - A new topical treatment for acute herpetic neuralgia and post-herpetic neuralgia: the aspirin/diethyl ether mixture. An open-label study plus a double-blind controlled clinical trial. AB - Topical aspirin/diethyl ether (ADE) mixture was used to treat 45 consecutive patients with acute herpetic neuralgia (AHN) (n = 28) and with post-herpetic neuralgia (PHN) (n = 17) in an open-label study. Good-to-excellent results were achieved by 93% of AHN patients and by 65% of PHN patients. Earlier treatment yielded better results for the AHN but not the PHN group. The topical treatment seemed to accelerate the healing of acute herpetic skin lesions and possibly modulate the severity of the herpetic infection. Furthermore, a striking reduction in the percentage of AHN patients developing PHN was observed in the treated group, as compared with the disease natural history reported in the literature (4 vs. 50-70%). Treatment tolerance was excellent with no adverse effect observed. In addition to the open trial, a pilot double-blind crossover placebo-controlled study (n = 11) compared the analgesic efficacy of ADE with two other NSAID (indomethacin and diclofenac) drug/ether mixtures. Aspirin (but not indomethacin and diclofenac) was significantly superior to placebo as regards pain relief (P less than 0.05). PMID- 1594262 TI - Diclofenac does not modify morphine bioavailability in cancer patients. AB - We determined morphine plasma concentrations in 6 cancer patients before and with administration of diclofenac for 5 days. The non-steroidal anti-inflammatory drug does not modify morphine bioavailability. This observation suggests that diclofenac can be used in association with morphine during cancer pain treatment, without increasing the risk of overdosage or side effects of the opiate. PMID- 1594263 TI - Transdermal clonidine versus placebo in painful diabetic neuropathy. AB - In a randomized, double-blind, 2-period crossover study, 24 patients with pain due to diabetic polyneuropathy received transdermal clonidine, 0.3 mg/day, and placebo patches, each for 6 weeks. Pain was assessed daily by a 13-word descriptor list. Mean daily pain scores for the 6th week, the primary outcome variable, averaged 13% lower with clonidine than with placebo (95% conf. lim. for clonidine effect: 29% reduction to 3% increase in pain), which was not statistically significant (P = 0.11, 2-tailed paired t test). After this study, however, 9 patients who wished to continue clonidine had single (3 patients) or multiple (6 patients) cycles of clonidine withdrawal and rechallenge. Seven of 9 patients consistently reported return of pain with patch withdrawal followed by relief upon retreatment. One patient had an equivocal response, and the other patient had no relief upon retreatment. The 7 responders appeared similar to the other 17 patients in pain quality and neurological exam. We conclude that there may be a subset of patients with diabetic polyneuropathy who respond to transdermal clonidine. Further research is needed to identify features of neuropathic pain that predict drug response and to develop study designs that are more sensitive to a response in a subset of patients. PMID- 1594264 TI - Therapists and therapies for post-thoracotomy neuralgia. AB - An unknown number of patients who undergo thoracic surgery develop post thoracotomy neuralgia (PTN). Many seek a cure. As with other chronic, benign pain conditions, a variety of treatment modalities may be offered by different specialists. Results of therapy in terms of patient satisfaction are not known. A record of 73 patients with PTN was made. It has been used to measure the incidence, the natural and therapeutic history and the success of the management of PTN. Over 70% of the cases received three or more of the treatment modalities and regimens that have been reputed to be of value. More than 50% were referred to three different types of specialist. No patient claimed to have become free of symptoms as a result of treatment and a significant proportion, not clearly defined, implied that therapy was either more disabling than PTN or made it worse. Side effects of drugs were blamed for the former, and invasive treatments, aimed at nociceptive pathways, were incriminated in the latter. It is reasoned that about 5% of patients undergoing thoracic surgery may require resources for the management of PTN. No patient studied thought that conventional treatments had brought about a cure. Some treatments, known to be deleterious, remain extant. This information reflects and corroborates that from other studies which suggests that multidisciplinary approaches are more appropriate for chronic benign pain conditions than management by isolated physicians using specific therapies. PMID- 1594265 TI - Identification and characterization of afferent periodontal C fibres in the cat. AB - The presence of afferent periodontal C fibres was studied in pentobarbitone anaesthetized cats. Extracellular single-fibre recordings were made from fine nerve filaments split from the proximally cut end of the inferior alveolar nerve. Periodontal nerve fibres were identified by constant-current stimulus pulses applied via platinum wire electrodes inserted into the periodontal space. Of 260 periodontal nerve fibres, 142 (55%) were classified as C fibres according to their conduction velocities (less than or equal to 2.5 m/sec) as determined by electrical stimulation of the periodontal ligament (c.v.p). The mean (+/- S.D.) c.v.p was 1.2 +/- 0.6 m/sec (n = 142; range: 0.3-2.5 m/sec). In addition, the axonal conduction velocity of 14 periodontal C fibres was determined by bipolar electrical stimulation of the trunk of the inferior alveolar nerve (c.v.n). On average the c.v.n was 42% higher than the c.v.p; the mean value was 1.7 +/- 0.8 m/sec (n = 14; range: 0.6-3.9 m/sec). Nevertheless, the classification of nerve fibres based on c.v.p proved to be reliable; only 1 fibre had a c.v.p less than 2.5 m/sec and a c.v.n greater than 2.5 m/sec and a c.v.n greater than 2.5 m/sec and was therefore reclassified as an A delta fibre. The responses of 30 electrically identified periodontal C fibres were tested by mechanical, thermal and chemical stimuli applied to the periodontal space. Thirteen of 19 periodontal C fibres tested responded to a strong mechanical force applied to the tooth from different directions while none could be activated by slight touch. A rudimentary directional sensitivity was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594266 TI - Rat knee-joint carrageenin incapacitation test: an objective screen for central and peripheral analgesics. AB - A new behavioral test is described in which quantitation is independent of the observer and is sensitive to all classes of analgesics. A computer-assisted device measures the period during which a rat hind paw fails to touch the surface of a rotating cylinder for 1 min (paw elevation time). Intra-articular injection of carrageenin induces a progressive and dose-dependent incapacitation of the limb. The maximum paw elevation time is attained 3-4 h after carrageenin challenge. The model showed dose-dependent sensitivity to (a) a central acting opiate (morphine, ID50 = 1.5 mg/kg, i.p.), (b) cyclooxygenase inhibitors (indomethacin, ID50 = 0.8 mg/kg, i.p.; diclofenac, ID50 = 0.22 mg/kg, i.p.), and (c) peripheral analgesics which directly antagonize nociceptor hypersensitivity: dipyrone (ID50 = 21 mg/kg, i.p.), N-methyl-nalorphine (ID50 = 14 mg/kg, i.p.) and BW443C (ID50 = 17.5 mg/kg, i.p.). The knee-joint carrageenin incapacitation was also blocked by the sympatholytics, propranolol and guanethidine. After the blockade by either indomethacin or guanethidine, intra-articular injections of prostaglandin E2 or dopamine, respective, reversed carrageenin-induced incapacitation. These results suggest that during inflammatory articular incapacitation cyclooxygenase and sympathomimetic mediators are involved, as has been suggested for the rat paw carrageenin hyperalgesia test and formalin test. PMID- 1594267 TI - Antinociception induced by electrical stimulation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group of the rat. AB - Recent anatomical evidence indicates that the pontine A7 catecholamine cell group provides the major noradrenergic innervation of the spinal cord dorsal horn (laminae I-IV). The experiments described in this report were designed to determine if these neurons modulate nociception at the level of the spinal cord. To this end, the antinociceptive effect of electrical stimulation applied at various sites along several tracks through the dorsolateral pontine tegmentum was determined in lightly anesthetized rats. The latency of the withdrawal response of the hind feet to noxious radiant thermal stimulation applied to the dorsal surface was used as a measure of nociception. The results indicated that the most potent and consistent antinociception was produced at sites near the A7 cell group. In addition, intrathecal injection of alpha-noradrenergic antagonists blocked the antinociception produced by electrical stimulation at sites near the A7 group. These observations indicate that the antinociception produced by stimulation near the A7 cell group was mediated by spinally projecting noradrenergic neurons. The results of these experiments provide evidence that pontospinal noradrenergic neurons located in the A7 cell group are important components of the descending neuronal system that modulates nociception. PMID- 1594268 TI - The relationship between pain sensitivity and blood pressure in normotensives. AB - Hypertension has been found to be related to decreased sensitivity to painful stimuli. The current study explored whether this relationship extends into the normotensive range of blood pressures. Resting blood pressures were assessed in 60 male normotensives. Subjects then underwent a 1 min finger pressure pain stimulation trial. Pain ratings were inversely related to resting systolic blood pressure. This relationship was unrelated to emotional state or coping styles. Multiple regression analyses indicated that over one-third of the variance in pain ratings can be accounted for by resting blood pressure, coping style, and emotional state. PMID- 1594269 TI - Topical reviews: a new type of report in PAIN. PMID- 1594270 TI - Analgesia produced by lidocaine microinjection into the dentate gyrus. AB - The local anesthetic lidocaine was injected into the dentate gyrus (DG) of alert, unrestrained rats 10 min prior to investigation within the formalin test. Regional anesthesia of the DG resulted in a reduction of pain scores when administered contralateral to the site of subcutaneous formalin injection. The analgesic effect was evident 30-50 min after central infusion. These results provide evidence of the involvement of the hippocampal formation (HF) in pain perception. PMID- 1594271 TI - Central changes of beta-endorphin-like immunoreactivity during rat tonic pain differ from those of purified beta-endorphin. AB - Several studies have described changes in beta-endorphin-like immunoreactivity (beta-ELI) in the rat brain in response to pain and stress stimuli. In order to ascertain the components of beta-ELI, brain samples of rats experiencing acute prolonged (tonic) pain were evaluated for their beta-ELI and later submitted to a chromatographic purification allowing the measurement of beta-endorphin (beta-EP) and acetyl beta-EP. The chromatographic analysis of both ventromedial hypothalamus (VMH) and periaqueductal grey (PAG) homogenates indicates that beta ELI is distributed in several fractions including shortened forms of beta-EP and their respective acetylated compounds. Quantitatively, while beta-ELI in formalin injected animals was increased by 48% in VMH and 45% in PAG in respect to controls, the net increase of purified beta-EP was 1100% and 470%, respectively, for VMH and PAG. Moreover, the maximal increase of beta-ELI was evident at 120 min, in both tissues. In contrast, the beta-EP peak was reached at 30 min in VMH and at 60 min in PAG. Acetyl beta-EP was unchanged by treatment in both central areas. No correlation of beta-ELI and beta-EP was found in VMH. These data demonstrate that the evaluation of beta-ELI gives a poor estimate of beta-EP changes, due to several components of the endorphin family. PMID- 1594272 TI - Further evidence for the existence of long ascending unmyelinated primary afferent fibers within the dorsal funiculus: effects of capsaicin. AB - The present study provides further evidence in support of the hypothesis that there is a fine primary afferent system in the dorsal funiculi by determining the effects of capsaicin (8-methyl-N-vanillyl-6-noneamide) on unmyelinated fibers in the cervical fasciculus gracilis of the rat. The neurolytic effect of this procedure was demonstrated by showing an 89% decrease in the number of unmyelinated fibers in the S2 dorsal roots of the experimental animals. Consequently, we feel that unmyelinated primary afferent fibers are largely removed from these animals. Neonatal administration of capsaicin (50 mg/kg) caused a 54% decrease in the number of unmyelinated fibers in the C3 fasciculus gracilis but no significant change in myelinated fiber numbers. The data provide further evidence for the existence of a significant primary afferent unmyelinated fiber system in the dorsal funiculus and suggest a role for the dorsal funiculi in the transmission of noxious information. PMID- 1594273 TI - Spinal pharmacology of thermal hyperesthesia induced by constriction injury of sciatic nerve. Excitatory amino acid antagonists. AB - This study evaluated the effects of spinally administered excitatory amino acid antagonists on the thermal hyperesthetic state induced by unilateral partial ligation of the sciatic nerve in the rat. The measured response was the latency to paw withdrawal of each hind paw after application of a focused heat lamp on the plantar surface of the paw through a glass plate upon which the animal stood. In this work, antagonists (MK801, DL-2-amino-5-phosphonovalerate, ketamine) of the N-methyl-D-aspartate receptor (NMDA), the glycine potentiation site at the NMDA receptor (5-chloro-indole-2-carboxylic acid) and non-NMDA receptor (kynurenic acid: g-D-glutamylaminomethyl sulphonate) were injected through chronically implanted lumbar intrathecal catheters in normal rats (no lesions) and in rats with unilateral constriction injury. In the normal rat study, NMDA and non-NMDA antagonists had little effect upon paw withdrawal latency at intrathecal doses which did not produce readily detectable motor weakness. In the hyperesthetic rat study, NMDA antagonists would temporarily eliminate the hyperesthetic state at doses below those which altered the response latency of the normal paw or which altered motor function. These results suggested that spinal NMDA receptors play an important role in the hyperesthetic state induced by peripheral nerve injury. PMID- 1594274 TI - Systemic morphine administration attenuates the perceived intensity of noxious heat in the monkey. AB - We examined the ability of systemic morphine to diminish the sensory discriminative features of noxious heating. Monkeys were trained to perform a thermal detection task, and the time until their detection of small increases in heating was used as a measure of the perceived intensity of pain. Relatively small doses of morphine sulfate (0.1, 0.3 and 1.0 mg/kg, i.m.) increased the time until detection of graded temperature increases (0.4-1.0 degrees C) from a noxious 46 degrees C baseline. These effects were generally dose-dependent, reversed by systemic naloxone, and did not result from changes in attentional, motivational or motoric aspects of the monkeys' behavior. Furthermore, the effects of morphine were more pronounced on detection of temperature shifts that were near threshold. These findings indicate that doses of morphine in the therapeutic dose range for humans alter the perceived intensity of noxious heat in monkeys. PMID- 1594275 TI - Octreotide: a potent new non-opiate analgesic for intrathecal infusion. AB - Somatostatin-14 has been reported to relieve severe cancer pain when given intraspinally. We have studied a stable analog, octreotide, which is suitable for long-term infusion by a drug pump. In preclinical trials in dogs, chronic intrathecal and intraventricular perfusion at 40 micrograms/h did not produce neurotoxicity. On the basis of these findings cancer patients with pain unrelieved by oral opiates were treated for periods of 13 to 91 days with intrathecal octreotide 5-20 micrograms/h. During octreotide infusion, pain scores were lower while oral opiate usage was reduced. No central or systemic side effects of intrathecal administration were seen. The pain relief occurred in patients who had previously not obtained satisfactory pain control with systemic or intrathecal opiates, which is consistent with a non-opiate spinal pathway. These preliminary findings, if confirmed, suggest that octreotide is a potent non opiate analgesic appropriate for long-term intrathecal infusion. PMID- 1594276 TI - Antinociceptive and motor effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. AB - This study investigated antinociceptive effects of intrathecal morphine combined with intrathecal clonidine, noradrenaline, carbachol or midazolam in rats. Each animal received intrathecally, on 3 separate occasions (i) 2 micrograms morphine (M), (ii) a dose (D) of one of the non-opioid drugs, and (iii) a combination, 1/2(M+D), consisting of 1 microgram morphine plus half the dose of the non-opioid drug. Antinociceptive effects were assessed by the hot-plate and tail-flick tests over the duration of drug action. All non-opioid drugs studied led to dose related antinociceptive effects when given alone. Addition of morphine caused a left shift in the dose-response curves of all the non-opioid drugs, indicating at least some degree of additive effects. Effects were considered supra-additive when the effect of the combination, 1/2(M+D), was significantly greater than both the effect of 2 micrograms morphine and the dose of non-opioid. Evidence of supra additive antinociceptive effects was obtained only with the clonidine-morphine combination. PMID- 1594277 TI - The non-sensory basis of autotomy in rats: a reply to the editorial by Devor and the article by Blumenkopf and Lipman. PMID- 1594278 TI - Response of intractable pain to continuous intrathecal morphine: a retrospective study. AB - We have treated 37 patients with intractable pain (35 with cancer-related pain) by continuous intrathecal morphine infusion via implanted pump. These patients were carefully selected according to specific criteria, and each demonstrated a significant reduction in pain following a test dose of intrathecal morphine. All patients had good pain relief from intrathecal morphine infusion, even with pain located in cervical dermatomes. Systemic narcotics could be withdrawn from most patients. Significant side effects were rare and typically self-limited. Many patients required gradually increasing doses, seemingly related to disease progression. Two patients with non-malignant pain have had variable dose requirements over 28 and 44 months without clear tolerance. In these patients we observed a reduction in side effects associated with systemic opioids when continuous intrathecal opioid infusion was instituted. Intrathecal opioid administration may have fewer complications than ablative pain relief procedures. In properly selected patients, this method offers an effective alternative for pain relief. PMID- 1594279 TI - Chronic pain induces a paradoxical increase in growth hormone secretion without affecting other hormones related to acute stress in the rat. AB - In several diseases chronic pain is associated with long-lasting pathophysiological responses which differ strongly from those observed in acute situations. When persisting, acute pain often results in physical and psychological stress which may in turn aggravate the initial pathological state. In the present work we examined the secretory patterns of pituitary hormones related to acute stress (growth hormone (GH), prolactin (PRL) and beta-endorphin (beta-END)) in rats during the phase of Freund adjuvant-induced arthritis (AIA, a model used for chronic pain studies) when chronic pain is maximum (14 and 21 days, postinoculation (PI)). Using radio-immunoassay hormones were measured in plasma samples taken every 30 min for 7 h in free-moving rats 14 and 21 days after Freund adjuvant or vehicle injection and in control animals. The total amount of GH secretion was higher at 14 and 21 days PI in AIA rats as compared to vehicle-treated and control animals, and the pulsatility of GH secretory pattern was not modified by AIA. PRL and beta-END secretion were not significantly different in arthritic rats as compared to controls. These results show that GH, PRL and beta-END responses induced by acute stress are not observed during the AIA phase when chronic pain is maximum. Thus, in our experimental conditions, beta-END and PRL do not seem to be good plasma markers of chronic pain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594280 TI - Self-administration of midazolam for postoperative anxiety: a double blinded study. AB - Anxiety is almost inevitably present in patients facing surgery. The optimal management of postoperative pain requires the acknowledgement of perioperative anxiety and the inclusion of pharmacological and/or non-pharmacological means of alleviating the fear and worry inherent in the surgical experience. In a double blind randomized design, 39 patients undergoing total abdominal hysterectomies were given postoperative access to a standard patient-controlled analgesia (PCA) morphine pump for pain and a PCA pump dispensing either low-dose midazolam or saline for anxiety. Measures of anxiety and pain were completed pre-operatively and for 2 days postoperatively. Utilization of morphine and 'anxiolytic agent' were recorded. Analysis of covariance was applied to the data to control for the imbalance of cancer patients between the 2 groups. While both groups of patients chose to utilize their 'anxiety pump' throughout the study, those patients receiving midazolam had significantly lower postoperative Spielberger State Anxiety scores and visual analogue scale anxiety scores. Patient-controlled midazolam in doses used in this study were safe and effective in managing anxiety but did not influence pain scores or the amount of PCA morphine patients used. Pre-operative levels of depression were significantly associated with postoperative pain levels independent of treatment group or cancer diagnosis. PMID- 1594281 TI - Spinal local anaesthetic actions on afferent evoked responses and wind-up of nociceptive neurones in the rat spinal cord: combination with morphine produces marked potentiation of antinociception. AB - Lignocaine was tested either alone or in combination with a low dose of morphine by intrathecal administration on the C- and A-beta evoked responses of nociceptive neurones in the dorsal horn of the halothane-anaesthetized rat. In addition the effect of prilocaine was compared to lignocaine. The effects of lignocaine on wind-up, a frequency-dependent increase in the responses of the cells produced by repeated C-fibre stimulation was also tested. Lignocaine produced dose-dependent inhibitions of the C-, A-delta and A-beta evoked responses of the cells which became more selective for the noxious evoked responses as the dose increased. The effective doses corresponded well to those used clinically. Wind-up was also decreased by lignocaine. In combination with a low dose of morphine, threshold doses of lignocaine produced a highly marked potentiation of the inhibitions of the C-fibre evoked responses compared to either agent alone. No potentiation of the inhibitions of the A-beta responses was observed. The potentiated inhibitory effects on the C-fibre responses were rapidly reversed by intrathecal naloxone. The finding that spinal local anaesthetic and morphine potentiate markedly to reduce spinal nociception is discussed both in terms of mechanisms of action of the agents and their clinical application. PMID- 1594282 TI - Psychophysical examination of pain induced by defined CO2 pulses applied to the nasal mucosa. AB - In 12 volunteer subjects, noxious chemical stimulation was performed by applying precisely controlled CO2 pulses to the nasal mucosa. Each subject participated in 2 identical psychophysical sessions including: (1) determination of the pain threshold, (2) determination of stimulus response functions to different durations of CO2 pulses with fixed concentration and (3) determination of stimulus response functions to different concentrations of CO2. In this test we also examined the relative sensitivity of the visual analogue scale (VAS) and the magnitude estimation (ME) procedure. The reliability of the psychophysical data was tested by comparing the results obtained in both sessions. The intra individual variability of the pain threshold was rather low. All the CO2 pulse widths used induced phasic pain sensations which when averaged encoded stimulus durations of up to 1 sec. Longer application periods did not further increase the pain sensations. The stimulus response functions to different concentrations of CO2 could be described well with Stevens' power functions. In our hands the VAS and ME procedures proved to be equally sensitive. The obtained psychophysical data appeared to be rather reliable since no significant differences in the ratings obtained in both sessions could be observed. PMID- 1594283 TI - Dynamic training and circulating neuropeptides in rheumatoid arthritis: a two year follow-up study. AB - Previous research has suggested that a short-term (6 week) high-intensity and a subsequent long-term (1 year) low-intensity dynamic training programme in 8 patients with rheumatoid arthritis (RA) increased circulating levels of beta endorphin (beta-EP) during the high-intensity training and of corticotropin releasing factor (CRF) and beta-lipotropin (beta-LPH) levels during the low intensity training, without an increase of pain experience. The present follow-up study of the patients, using the data obtained after an additional 1-year period of no standardized training as reference values, indicated that CRF levels decreased significantly (P less than 0.01) in relation to those obtained 1 year earlier. For beta-LPH and beta-EP, no corresponding decreases were noted. No significant difference concerning experience of pain over time was found. High performance liquid chromatography demonstrated a complex elution pattern with low basal concentration of beta-LPH, which increased after 60 min of training. PMID- 1594284 TI - Chronic abdominal pain and depression. Epidemiologic findings in the United States. Hispanic Health and Nutrition Examination Survey. AB - We report data on abdominal pain and depression from a survey of Hispanic Americans by the United States National Center for Health Statistics. The point prevalence rates of chronic abdominal pain were 4.6% in Mexican Americans and 5.8% in Cuban Americans in a total of 4175 subjects. The rate was 8.3% among 1323 Puerto Ricans. In 53% the abdominal pain came in waves. Using the Depression scale of the Center for Epidemiologic Studies (CES-D), 18.7% of Mexican and Cuban Americans with pain were found to be depressed to an extent likely to require intervention, and 40.8% of Puerto Ricans were so affected. The Diagnostic Interview Schedule (DIS) gave more conservative figures for major depression in terms of DSM-III, viz., 6.8% for Mexican and Cuban Americans with chronic pain, and 12.6% for Puerto Ricans with chronic pain. Logistic regression analyses demonstrated links between depression and female sex, the single state, low education and income, and chronic abdominal pain. The most consistent relationships for depression were with chronic pain, female sex and the single state. The results confirm the strong relationships between chronic pain, mood and female gender, and other socio-demographic variables. PMID- 1594285 TI - Pain response to perineuromal injection of normal saline, epinephrine, and lidocaine in humans. AB - In animal neuroma models the application of alpha-adrenergic agonists causes a burst of spontaneous afferent activity. The increased activity has been hypothesized to generate nociceptive input. Corroborative work in humans, however, has not been done. Nine subjects with chronic nerve end neuromas received perineuromal injections of normal saline, epinephrine (5 micrograms), and lidocaine in a blinded manner. Qualitative and quantitative pain assessments were performed with each injection. Epinephrine, but not saline, caused an intense increase in reported pain with subjects often commenting that the appendage was "on fire". Lidocaine significantly reduced but did not completely abolish the reported pain. The chemosensitivity of the neuroma to epinephrine may explain some of the clinical responses noted after sympathetic system manipulation. It is likely that alpha-adrenergic sensitivity is only one of many components sustaining or exacerbating pain after nerve injury. PMID- 1594286 TI - Statistical analysis of drug combinations for synergism. PMID- 1594287 TI - Aggregation and stability in parasite-host models. AB - This paper generalizes the two-dimensional approximation of models of macroparasites on homogeneous populations developed by Anderson & May (1978), focusing on how the dispersion (the variance to mean ratio) of the equilibrium distribution of parasites on hosts is related to the stability of the equilibrium. We show in the approximate system that the equilibrium is stabilized not by aggregation, but by dispersion which increases as a function of the mean. Computer simulations indicate, however, that this analysis fails to capture properly the dynamics of the full system, raising the question of whether any two dimensional system could produce an adequate approximation. We discuss the relevance of our results to several empirical studies which have examined teh relation of dispersion to the mean. PMID- 1594288 TI - Preliminary biochemical characterization of 'veil' structure purified from Theileria sergenti-, T. buffeli- and T. orientalis-infected bovine erythrocytes. AB - A structure called 'veil' in Theileria sergenti-, T. buffeli- or T. orientalis infected bovine erythrocytes was purified from erythrocyte lysates by Percoll density-gradient centrifugation. On electron microscopical examination, the veils consisted of electron-dense material showing a periodicity of striations and were not surrounded by membranes. Analyses of veil proteins by one- and two dimensional polyacrylamide gel electrophoresis revealed that the veils contain haemoglobin and several other basic proteins of molecular weight ranging from 15.5 to 46 kDa. By comparing the protein patterns of the veil with those of purified piroplasms and uninfected bovine erythrocytes, these basic proteins appeared to be of parasite origin. It would appear likely that the veils formed by intra-erythrocytic precipitation of haemoglobin and proteins excreted by the parasites. Differences in veil constituents were found between T. sergenti, T. buffeli and T. orientalis. PMID- 1594289 TI - Relationship between body size of adult Anopheles gambiae s.l. and infection with the malaria parasite Plasmodium falciparum. AB - The influence of adult female body size of Anopheles gambiae s.l. on development of midgut and salivary gland infections by the parasite Plasmodium falciparum was investigated in a field study carried out in Tanzania. The proportion of mosquitoes infected during a blood meal was independent of size. However, the number of oocysts harboured by infected mosquitoes increased with size of the mosquito. The proportion of mosquitoes with sporozoites, and thus potentially infective to humans, was highest in intermediate-sized mosquitoes, whereas the largest and smallest mosquitoes were less likely to have sporozoites. This pattern is interpreted as a combination of high survival rate of large, uninfected mosquitoes and of low survival rate of mosquitoes infected with many oocysts. PMID- 1594290 TI - Ribosomal DNA sequences in the differentiation of pathogenic and non-pathogenic isolates of Entamoeba histolytica. AB - Recombinant ribosomal DNA sequences were amplified by PCR and used as probes to perform a fingerprint analysis of total DNA from different Entamoeba histolytica isolates. RFLPs obtained with one of the probes, R-1, support previous proposals that pathogenic and non-pathogenic E. histolytica are closely related, yet genotypically distinct. Another probe, R-2, while not distinguishing between the two forms of E. hystolytica, was able to differentiate between them and E. moshkovskii, which has morphologically identical cysts and trophozoites. A third probe, BR-1, identified strain-specific RFLPs. PMID- 1594292 TI - Long-term dynamics of natural populations of Schistosoma mansoni among Rattus rattus in patchy environment. AB - Dynamics of natural populations of Schistosoma mansoni were studied during 8 consecutive years among Rattus rattus populations from 8 transmission sites of the marshy forest focus of Guadeloupe (French West Indies). The schistosome population is over-dispersed (k = 0.119) within the murine hosts and ecological factors linked to the patchy environment may be responsible for such aggregated distribution. Analysis of the spatio-temporal variations in prevalences, intensities and abundances showed limited variations of the infection during the 8 years at the level of the whole parasite population but great spatial heterogeneity at the level of local schistosome populations. Inter-populational genetic variability linked to the degree of adaptation of this human parasite to the murine host may explain differences in transmission dynamics between the local populations of S. mansoni. PMID- 1594291 TI - Age-related differences in parasitosis may indicate acquired immunity against microfilariae in cattle naturally infected with Onchocerca ochengi. AB - Onchocerca ochengi is a common parasite of cattle in savanna areas of West Africa and its adult stages inhabit intradermal nodules. We have exploited the accessibility of the macrofilariae to examine quantitative and qualitative differences in both the macro- and microfilariae (mff) in relation to age in naturally infected cattle. Autochthonous cattle at a site on the Adamawa plateau, North Cameroon, situated near a perennial Simulium damnosum s.l. breeding site, were examined in three age groups (1.5-2.5, n = 34; 3-5, n = 39 and greater than or equal to 8 years old, n = 21). Skin mff densities were assessed from ventral skin biopsies, total body counts of nodules were done by palpation and 1-4 nodules were excised from positive animals, collagenase digested and the numbers and condition of macrofilariae determined. Embryogenesis profiles (embryograms) were done on a representative number of female worms in each age group. The overall prevalence of infection in the study population was 71% for mff and 85% for nodules. Nodule prevalence increased significantly from the 1.5-2.5 to 3-5 years old groups, but no other inter-age prevalences were significantly different. While the mean number of nodules per animal increased with age, geometric means (gm) 3.7, 15.5 and 23.1, the skin mff density maximized in the middle age group and decreased significantly in the old animals (gm 15.8, 44.7 and 11.4 mff/g, difference between latter two parameters significant, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594293 TI - The role of mononuclear-cell recruitment to the lungs in the development and expression of immunity to Schistosoma mansoni. AB - The role of pulmonary cellular responses in the induction and expression of immunity to Schistosoma mansoni has been evaluated. From experiments in which mice were challenged at intervals after vaccination, we conclude that the resistance mechanism operating in the lungs develops between days 11 and 20. Injection of 51Cr-labelled splenocytes revealed that mononuclear cell recruitment to the lungs, stimulated by the arrival of attenuated schistosomula, intensified progressively between days 10 and 16 post-vaccination. The increased cellularity was reflected in a 19.5% augmentation in the wet-weight index (WW). The period of enhanced cell recruitment therefore coincided with the build-up of resistance. By day 22 post-vaccination infiltration had declined, whilst WW remained elevated. This indicates the persistence of recruited cells, which include schistosome reactive T lymphocytes, in the lungs. We were unable to demonstrate augmented recruitment of 51Cr-labelled cells after challenge of vaccinated mice, but WW rose slightly, peaking on day 12. Although clearly of a lower order than the primary response, the secondary response was more rapid, implying the existence of immunological memory. These results accord with the concept that schistosome reactive T lymphocytes recruited after vaccination 'arm' the lungs against the arrival of challenge parasites. PMID- 1594294 TI - In vitro release of the anti-gonadotropic hormone, schistosomin, from the central nervous system of Lymnaea stagnalis is induced with a methanolic extract of cercariae of Trichobilharzia ocellata. AB - Infection with digenetic trematodes causes an inhibition or complete cessation of fecundity in their intermediate hosts, freshwater snails. It has been demonstrated in the host-parasite combination Lymnaea stagnalis-Trichobilharzia ocellata that the action of the female gonadotropic hormones upon their target organs is inhibited by the peptide schistosomin. Schistosomin is produced in the central nervous system of the snail and released upon parasitic infection. In order to study the in vitro release of schistosomin, a bioassay was developed. Central nervous systems were incubated with either an acetic acid or a methanolic extract of larval stages of Trichobilharzia ocellata (miracidia, mother sporocysts, cercariae). The incubation media were chromatographed using HPLC and released schistosomin (-like material) was tested for bioactivity in the calfluxin bioassay. The in vitro release of schistosomin was only induced with a methanolic extract of cercariae. The nature of the cercarial factor is discussed. PMID- 1594295 TI - Detection of peptidases in Trypanosoma cruzi epimastigotes using chromogenic and fluorogenic substrates. AB - Detergent extracts of Trypanosoma cruzi epimastigotes catalysed the hydrolysis of a range of amino-acyl and peptidyl p-nitro-anilides and aminomethylcoumarins. At least three enzymes were detected that cleave Z-Phe-Arg-MCA. Two of these were optimally active at alkaline pH, the other at pH 4.0. Of the two enzymes with alkaline pH optima, one was a cysteine peptidase and was unable to cleave Bz-Arg MCA readily, whilst the other cleaved Bz-Arg-MCA and was inhibited by diisopropyl fluorophosphate. The acidic enzyme was similar to cathespin L of other eukaryotes with respect to its pH profile, substrate-specificity and inhibitor-sensitivity. Evidence was presented that epimastigotes contain a cysteine-type dipeptidyl aminopeptidase, one or more aminopeptidases, and a serine peptidase that cleaves Boc-Ala-Ala-pNA. Digitonin solubilization of the activities from cells supports the hypothesis that the cathespin L-like enzyme and the dipeptidyl aminopeptidase are lysosomal, whilst the Bz-Arg-MCA hydrolase, the aminopeptidases and the Boc Ala-Ala-pNA serine peptidase are cytosolic. PMID- 1594297 TI - Behavioural adaptation of the tapeworm Hymenolepis diminuta to its environment. AB - Hymenolepis diminuta migrates up the small intestine in response to feeding the host 1 g of glucose. Locomotion during migration may result from fixed patterns of retrograde peristaltic-like waves in the strobila of the tapeworm which propel the organism against the normal expulsive forces in the small intestine. The peristaltic-like locomotory waves occur in a gradient along the strobila with a frequency of 24.9 +/- 0.9 cycles/min in the anterior segments of the worm, decreasing linearly to 6.6 +/- 1.4 cycles/min in the posterior segments of the worm. Chemical signals, isolated from the small intestine of fed hosts, which stimulate migration behaviour in vivo do not alter the behaviour of the scolex or strobila in vitro. Removal of the scolex containing the cerebral ganglia does not alter the frequency or pattern of locomotory activity in the strobila. After the worm is cut into pieces, each region generates the pattern of locomotory activity that is appropriate for that region. These data suggest that the peripheral nervous system, and not the central nervous system, is responsible for the coordination of the fixed patterns of locomotory activity in these tapeworms. PMID- 1594296 TI - Cloning and characterization of ribosomal RNA genes from Opisthorchis viverrini. AB - The ribosomal DNA (rDNA) unit of the liver fluke Opisthorchis viverrini has been cloned and characterized. The results demonstrated that the total length of this unit is approximately 13 kb, containing 4.2 kb of large subunit (LSU) rDNA, 2.0 kb of small subunit (SSU) rDNA, 1.0 kb of transcribed spacer DNA and 5.8 kb of non-transcribed + external transcribed spacer DNA. Examination of the non transcribed spacer region between different rDNA units showed variation in the restriction sites rather than in the length. Judging from hybridization of the rDNA plasmid to the restriction endonuclease digest of genomic DNA, rDNA units represent 6.1% of the total genomic DNA. At the RNA level, the LSU rRNA of O. viverrini and Fasciola gigantica contained a hidden break. The molecule consisted of two fragments co-migrating with a SSU rRNA, when electrophoresis was carried out under denaturing conditions. Ribosomal RNA sequence comparison has been previously used to determine phylogenetic classification of parasitic organisms. The sequence of 381 nucleotides at the 5' terminus of the LSU rRNA gene was determined and compared with those from species previously reported by other investigators. Phylogenetic classification of O. viverrini, as determined by rRNA gene sequence comparison, is comparable with the conventional taxonomic classification. PMID- 1594298 TI - Coproantigen detection for immunodiagnosis of echinococcosis and taeniasis in dogs and humans. AB - Three ELISA assays, based on hyperimmune rabbit serum raised against adult cestode somatic antigen, were applied in this study for the detection of Taenia- and Echinococcus-specific antigens in host faeces. The first assay, using an antiserum against Taenia pisiformis antigen extract, was used in a time-course of T. pisiformis experimental infection in dogs. The assay was shown to be considerably more sensitive than microscopical detection of eggs in faeces. Antigen was present in faeces before patency and antigen levels were independent of T. pisiformis egg output. The second assay, involving a test for human taeniasis based on antibodies against T. solium, was applied in two field studies carried out in China and Guatemala. The test was highly specific, no false positive reactions occurred with human faecal samples and the test was capable of diagnosing individuals who would not have been detected by coproscopy or treatment to recover the tapeworm. A third assay was designed for E. granulosus and demonstrated 87.5% sensitivity and 96.5% specificity with samples from naturally and experimentally infected dogs with Echinococcus or Taenia infections. In both the human Taenia and canine Echinococcus studies antigen could be detected in faecal samples from infected hosts stored in 5% formalin for 6 months. Further refinements to these tests for field application are discussed. PMID- 1594300 TI - Responses to larval Taenia taeniaeformis in mice with severe combined immunodeficiency (scid). AB - Responses to Taenia taeniaeformis infection were studied in mice with severe combined immunodeficiency (scid), which lack functional T and B lymphocytes. In the early phase of infection, accumulation of polymorphonuclear leucocytes (PML) occurred around the larvae in the liver of scid mice and their immunocompetent counterparts, C.B-17, (a BALB/c strain, genetically resistant to this parasite). PML accumulation continued until encapsulation of developing larvae by fibroblasts (14 days p.i.), and subsequent fibrosis resulted in granuloma formation. No infiltration of eosinophils or macrophages around larvae was observed in scid mice prior to granuloma formation, while in C.B-17 mice infiltration was observed as early as 5 days p.i., when specific antibodies could not be detected in the circulation. Most larvae were destroyed by 14 days p.i. in C.B-17 mice. In scid mice the larvae survived but the host capsules (cysts) were thin and most contained blood at 42 days p.i. In these cysts, inflammatory cells were observed on the larval surface and in invaded parasite tissue. Hepatocyte coagulation necrosis adjacent to larvae was commonly found in C.B-17 mice by 5 days p.i., while it did not occur in scid mice throughout these experiments. These results suggest that in host responses to larval T. taeniaeformis, PML accumulation and encapsulation by fibrosis are T and B cell independent, while eosinophil and macrophage infiltration, as well as resistance to infection, are T and/or B cell dependent. Additionally, there may be an association between host cell necrosis around larvae and T and/or B cell responses. PMID- 1594299 TI - Evaluation of a monoclonal antibody-based competition ELISA for the diagnosis of human hydatidosis. AB - An antibody competition enzyme-linked immunosorbent assay (ELISA) using 4 different monoclonal antibodies (MAb) raised against major antigens (Antigen 5 and Antigen B) of Echinococcus granulosus was evaluated for the diagnosis of human hydatidosis. The competition assay, using anti-Ag5 MAb 24.14, detected specific antibodies in 70% (131/188) of sera from patients with surgically confirmed E. granulosus infection and 38.5% (10/26) of sera from patients with E. multilocularis infection. None of the sera from patients with Taenia solium cysticercosis (10), T. saginata (2), filariasis (22), strongyloidiasis (19), fascioliasis (4), bilharziasis (4) and amoebiasis (2) tested were positive using a cut-off point established through reaction between MAb 24.14 and normal human sera. The combined use of the MAb 24.14-based competition ELISA with the conventional antibody-binding assay provides a highly sensitive (92.8%) and specific screening system for human hydatid disease diagnosis. PMID- 1594301 TI - The effect of repeated chemotherapy on age-related predisposition to Ascaris lumbricoides and Trichuris trichiura. AB - This study examines the persistence of predisposition to Ascaris lumbricoides and Trichuris trichiura during repeated chemotherapy in an urban community in Kuala Lumpur, Malaysia. Significant predisposition was observed over 2 periods of reinfection with and without age-standardization of data. Analysis of different age groups indicated that predisposition was most strongly detectable in the younger age classes. The intensities of infection with both parasites were strongly correlated at each cycle of intervention, suggesting that individuals were similarly predisposed to both species. PMID- 1594302 TI - A hypothesis for the higher incidence of vesico-ureteral reflux and primary megaureters in male babies. AB - The authors propose a new explanation for the male preponderance in cases with prenatally diagnosed vesico-ureteral reflux and primary megaureters. The theory is based on conclusions drawn from the characteristics of 4 patients (3 perinatal cases and 1 occurring in a 14-year-old boy) presenting with unusual anomalies of the lower urinary tract. In this hypothesis, the male preponderance could be related to an abnormal dilatation of the posterior urethra occurring during the embryological development of the male urethra. The dilatation leads to a flap valve mechanism and to a functional obstruction of the bladder outlet and finally to secondary dilatation of the upper urinary tract. This obstruction may be transitory; reflux and megaureters found in utero or after birth could be considered as sequellae of this phenomenon. PMID- 1594303 TI - Evaluation of abdominal pain in Henoch-Schonlein syndrome by high frequency ultrasound. AB - The authors report the use of high frequency ultrasound (7.5-10 MHz probes) for the detection of intestinal complications in 14 children with Henoch-Schonlein purpura. Ultrasound gave information of 3 levels: (1) It explained the acute abdominal pain by showing in all cases the oedematous haemorrhagic infiltration of the intestinal wall, which appeared thickened (3-11 mm): lesions were diffuse (6 cases) or focal (duodenal in 5 cases, jejunal in 2 cases and ileal in one). (2) It followed the evolution of the disease: extension of lesions (5 cases) or resolution (progressive decrease of parietal thickening, reexpansion of small bowel lumen, reappearance of peristalsis). (3) It always detected surgical complication: ileo-ileal intussusception (3 cases), perforation (1 case). PMID- 1594304 TI - Ultrasound diagnosis of midgut volvulus: the "whirlpool" sign. AB - The authors present their US findings in 24 patients with proved complicated midgut malrotation: volvulus in 18 and occlusive Ladd's bands in 6. All the 24 patients have had US examination prior to surgery. Contrast examinations were performed in only 9 patients, always after US and before surgery. The sonographic "whirlpool" pattern of the superior mesenteric vein and mesentery around the superior mesenteric artery was detected in 15 of the 18 patients with midgut volvulus, and was best seen using Doppler color. Embryological signification of midgut malrotation is discussed. PMID- 1594305 TI - Midgut malrotation, the reliability of sonographic diagnosis. AB - We are unaware of any other anatomical study which deals with normal variations in the relationship between the superior mesenteric artery (SMA) and the superior mesenteric vein (SMV). In our investigation in the majority of cases, the SMV lies to the right of the SMA. It has been suggested that ultrasonographic demonstration of a left sided SMV, is characteristic of midgut malrotation so a prospective study was undertaken in order to try to correlate the position of the mesenteric vessels on Ultrasound with the radiological diagnosis of midgut malrotation on upper GI series. 427 children (95% infants) who were planned for upper GI investigation, have had color Doppler U.S. of the mesenteric vessels before the barium study. In 67 cases, the mesenteric vessels were obscured by intestinal gas. Among them, there were 2 cases of malrotation. Three different positions of the mesenteric vessels were found in the 360 remaining cases. 1) A left sided SMV was found in 4% of the cases, all had midgut malrotation on X-rays and at surgery. 2) A mesenteric vein anterior to the SMA was found in 5% of the cases, 28% had midgut malrotation. 3) A normal right sided SMV was found in 91% of the cases. However 3% of these had midgut malrotation. There are anatomical variations in the position of the mesenteric vessels and a normal relationship between SMA and SMV does not exclude the possibility of intestinal malrotation. Nevertheless, ultrasound remains a useful noninvasive screening technique for the diagnosis of midgut malrotation. PMID- 1594306 TI - Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF) in meningitis and hemorrhage. Part I. Clinical evidence. AB - Using echographic flow imaging (colour Doppler), flow within ventricular CSF pathways was discovered in an infant with purulent meningitis. 22 mature and 40 premature infants were then investigated for presence of CSF-flow which was detected in a further 5 infants, all premature. Diagnostic criteria for echographic CSF-flow imaging are: 1. flow signals "within" CSF-pathways; 2. to and-fro movement of CSF (spectral analysis); 3. specific response of CSF-flow to stimuli (respiration, crying, abdominal palpation); 4. dynamic CSF-imaging related to specific anatomical areas of intracranial CSF-pathways. Echographic detection of CSF-flow depends on optimized adjustment of controls, equipment used, meticulous examination technique and awareness of pitfalls on the part of the examiner. A further prerequisite is the presence of scattering particles within CSF, such as red or white blood cells (minimum concentration in the order of one thousand cells/microL) or air. Although echographic CSF-flow imaging is not applicable for excluding the presence of disease, it appears to be a new diagnostic tool with considerable potential allowing selected early and non invasive diagnosis of CSF-pathology and giving new insights into CSF hemodynamics. PMID- 1594307 TI - Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF) in infants. Part II. CSF-dynamics. AB - 41 comprehensive colour Doppler studies (including spectral analysis) of the ventricular system were performed in 6 infants with CSF-flow (age range: 2 to 27 days). Two premature infants showed no evidence of disease related to the central nervous system (CNS). Overt intraventricular hemorrhage or CNS-infection were present in the other infants. All children were examined several times until CSF flow was no longer visible. The entire ventricular system, including the fourth ventricular outlet, was investigated for the presence of CSF-flow signals. Dynamic CSF-flow studies consisted of scanning during typical infant activity (crying, sucking, leg movement) and with external manoeuvres (abdominal or fontanellar palpation). CSF-flow was found to be: 1. synchronous with respiration 2. induced by rising intraabdominal (retrograde CSF-pulse) and transfontanellar pressure (orthograde CSF-pulse) 3. predominantly within the cerebral aqueduct, but also found at the foramina of Monro, within the third and fourth ventricles and at the foramen of Magendie. CSF-flow was not detected at the foramina of Luschka or within the lateral ventricles, except adjacent to the foramina of Monro. Dynamic CSF-flow as observed in infants may have important clinical and scientific implications. Examples of this are activity-related ventricular "reflux" of bacteria, erythrocytes, drugs, radionuclides or contrast; the importance of CSF-flow pulses for the development or progression of hydrocephalus; flow dynamics at the fourth ventricular outlet foramina and the study of CSF-pulse wave velocity and regional compliance. These issues are discussed and the new diagnostic approach is compared with other methods of CSF investigation. PMID- 1594308 TI - Colour-coded echographic flow imaging and spectral analysis of cerebrospinal fluid (CSF). Part III. In-vitro study of low flow velocity detection related to decreasing particle concentration (hematocrit) and tube lumen. AB - An in-vitro steady flow system was designed to determine the lowest flow velocities that can be detected by echographic colour flow imaging and spectral analysis. The flow detection level was determined hydrostatically by reducing the fluid level to below the point at which a flow signal was visible, then increasing the height until the colour flow reappeared. This was confirmed in all instances by spectral analysis. The height (angle-corrected velocity) of the spectral envelope was also determined. Mean volume flow was then obtained by using a graduated cylinder and a stop watch. The lowest hematocrit detectable was identified using a stepwise dilution of packed human red blood cells with 0.9% sodium chloride. Three different PVC-tubes with inner diameters of 2.1 mm, 1.1 mm and 0.51 mm were used.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594310 TI - Problems associated with digital luminescence radiography in the neonate and young infant. Problems with digital radiography. AB - An evaluation of the Siemens Digiscan has been undertaken to determine whether digital luminescence radiography (DLR) could replace conventional radiography in the examination of the neonate and young infant. Whilst the overall image quality of the digital radiograph was consistently higher than for conventional radiography the difference was less marked than we had expected. Furthermore, the potential for reduction in radiation dose by reducing the repeat rate due to incorrect exposure was limited. The potential advantages of DLR have been critically examined in relationship to neonatal radiography and a number of problems encountered during the evaluation have been highlighted. PMID- 1594309 TI - Noninvasive blood flow measurement and quantification of shunt volume by cine magnetic resonance in congenital heart disease. Preliminary results. AB - Based on the phase difference method as described by Nayler et al. we developed a gradient-echo sequence, which refocuses flow related phase shifts even for infants with their higher peak velocity, higher acceleration and faster heart rates. A repetition time (TR) of 15 ms provides a high temporal resolution for dynamic studies. Modification of the flow-rephasing gradient-echo sequence in slice select direction leads to a defined phase shift and the resultant phase difference images allow blood flow measurements in the great arteries and the calculation of blood volume per heart cycle (flow volume) to assess left and right ventricular stroke volume. This can also be achieved by calculation of the ventricular volume from contiguous slices of the whole heart, but, this in excessive measuring times. Both methods were applied in 6 examinations of children with congenital heart diseases (1 pulmonary sling, 1 coarctation of the aorta, 1 ventricular septal defect, 3 atrial septal defects). The age of the patients ranged from 3 months to 13.4 years (mean age 4.9 years). The regression analyses of both methods show a high correlation for systemic flow (y = -0.98 + 1.08 x, r = 0.99, SEE = 2.59 ml) and for pulmonary flow (y = -1.40 + 0.96 x, r = 0.99, SEE = 4.70 ml). The comparison of flow calculated Qp:Qs ratio and chamber size calculated Qp:Qs ratio with data obtained by heart catheterization show also a regression line close to the line of identity (y = -0.01 + 1.04 x, r = 0.98, SEE = 0.15 and y = 0.28 + 0.96 x, r = 0.81, SEE = 0.47, respectively). PMID- 1594311 TI - Connatal periventricular pseudocysts in the neonate. AB - Connatal periventricular pseudocysts are important sequelae of different noxious insults in the developing brain. Accurate diagnosis of those pathologic entities during early life has therefore become of direct concern to the clinician. Our experience with 12 infants of connatal periventricular pseudocysts provides the basis of this study. They belonged to different pathological entities: focal paraventricular pseudocysts (5 cases), subependymal pseudocyst (3 cases), connatal viral infection (3 cases), and chromosomal abnormality (1 case). When present at birth, they suggest an intrauterine pathology. It has only been with the advent of real-time cranial ultrasound that periventricular pseudocystic lesions can be detected in neonates following an abnormal pregnancy. Some obstetric complications during the second trimester can cause paraventricular or subependymal pseudocyst in the foetus. Neurotrophic viral infection and chromosomal abnormalities have also been implicated in the production of cystic lesions in this region. These lesions are not a terminal event in infants but may be a condition of major clinical importance for further neurological development. PMID- 1594312 TI - Diagnosis of neonatal aortic thrombosis by colour coded Doppler sonography. AB - We report on a neonate with complete aortic thrombosis following umbilical artery catheterization. Diagnosis was established by colour coded Doppler sonography which showed absent flow in the region distal to the thrombosis. After thrombolytic therapy with recombinant tissue plasminogen recanalization of the descending aorta could be shown by Colour Doppler imaging (CDI). PMID- 1594313 TI - Fluoroscopic catheter removal of blunt esophageal foreign bodies. A pediatric radiologist's perspective. AB - Fluoroscopic catheter removal of blunt esophageal foreign bodies is a safe, efficacious, time-effective, and cost-effective technique. PMID- 1594314 TI - Sonographic demonstration of annular pancreas and a distal duodenal diaphragm in a newborn. AB - A case of duodenal obstruction in a newborn is presented where sonographic examination demonstrated duodenal obstruction by both an annular pancreas and a duodenal diaphragm. PMID- 1594315 TI - An unusual CT presentation of congenital cerebral toxoplasmosis in an 8 month-old boy with AIDS. AB - We report on a 8-month-old boy with AIDS, born of an asymptomatic mother with positive HTLV-III serology. He was hospitalized in the Intensive Care Unit because of anemia, fever and hepatosplenomegaly. Chest X-ray showed pneumonia and subsequent blood cultures were positive for Candida albicans. After 3 days of Amphotericin B treatment, the patient was transferred to Infectious Disease Department. After 30 days of hospitalization, the patient developed a rapid neurological impairment evolving into coma. CT scan showed a round, ring-shaped low density lesion with hyperdense and enhancing haemorrhagic centre in the left basal ganglia and a smaller hypodense lesion on the right. There was also evidence of cortical atrophy and mild ventricular dilatation. Such lesions are more commonly described in children with AIDS and congenital cytomegalic inclusion virus (CMV) encephalitis. In this case toxoplasma cysts were shown microscopically reinforcing the contention that in patients with AIDS, toxoplasma gondii infection may occur with atypical manifestation. PMID- 1594316 TI - Spinal cord compression due to epidural extramedullary haematopoiesis in thalassemia. AB - A case of spinal epidural extramedullary haematopoiesis in thalassemia is reported. Role of computed tomography in this rare manifestation is emphasized with brief review of literature. PMID- 1594317 TI - Echogenic kidneys and medullary calcium deposition in a young child with glycogen storage disease type 1a. AB - We report the case of a young child with Glycogen Storage Disease (GSD) type-Ia who developed echogenic kidneys, medullary calcium deposition and disturbance of renal function. These severe renal abnormalities are seen in young adults whose GSD-I has been ineffectively treated. Renal disease can be considered a major problem in GSD-I. PMID- 1594318 TI - Haemangiomatous polyp of the posterior urethra in a boy. AB - Urethral haemangiomas are rare and usually involve the entire urethra or are localized to the anterior urethra. Posterior urethral polyps are uncommon. A posterior urethral polyp was removed from a 3-year-old boy which proved to be haemangioma. In the histological classification of posterior urethral polyps, haemangioma should therefore be included. PMID- 1594319 TI - Periventricular white matter cystic lesions in Lowe (oculocerebrorenal) syndrome. A new MR finding. PMID- 1594320 TI - Gaucher's disease. Plain radiography, US, CT and MR diagnosis of lungs, bone and liver lesions. AB - We report our observations made by conventional radiography, ultrasound, computerized tomography (CT), and magnetic resonance imaging (MRI) on a 3 1/2 year-old girl with Gaucher's disease. The interest of the case consists in the exceptional lungs involvement, the demonstration by MRI of the bone marrow involvement and the necrosis and fibrosis of the liver, as shown by CT. This liver complication has been previously reported only once. PMID- 1594321 TI - Infant apnea and gastroesophageal reflux. AB - The value of a combination of ultrasound studies and barium swallow examination in the analysis of temporal relationships between apnea and reflux is demonstrated. The two techniques allow acute apneic spells induced by gastroesophageal reflux to be documented and underlying specific digestive tract disorders demonstrated. The high incidence of digestive tract disorders in this area has been identified. PMID- 1594322 TI - Microgeodic phalangeal syndrome in an infant. AB - A new case is reported of the curious disease described by Maroteaux as Microgeodic phalangeal syndrome in infancy, of unknown etiology. The purpose of this communication is to describe an additional case of this rare condition, described for the first time by Maroteaux in 1970, and affecting the fingers of infants and children. The condition consists of a swelling of the fingers and multiple microgeodes in the phalanges. It is a benign disease and the lesions disappear totally after a few months. PMID- 1594323 TI - The mammalian glucose transporters. AB - We have described the properties of glucose transporters expressed in several mammalian tissues and have summarized some of the adaptations that take place involving these molecules in various normal and abnormal states. With the exception of a few cell types, such as adipocytes and skeletal muscle, glucose transport is not a rate-limiting step in cellular glucose metabolism, and other substrates may be equally important for cellular metabolism. Nevertheless, an understanding of the mechanisms behind the regulation of glucose transport in individual tissues may facilitate an understanding of in vivo glucose utilization and clearance processes as they relate to normal and disease states. Although adult studies provide an impetus toward a mechanistic approach in preventing and treating various disease states involving derangements in glucose homeostasis, there remains a need for similar studies in the fetus and newborn. These developmental studies should help unravel the fetal/neonatal responses to normal and abnormal hormonal and substrate milieu. PMID- 1594324 TI - Impact of prostaglandin and thromboxane synthesis blockade on disposition of group B streptococcus in lung and liver of intact piglet. AB - Group B streptococci (GBS) localizing in the lungs of infant piglets is killed in part by an oxygen radical-dependent mechanism (Bowdy BD, Marple SL, Pauly TH, Coonrod JD, Gillespie MN: Am Rev Respir Dis 141:648-653, 1990). The source of bactericidal oxygen radicals is unknown, but cyclooxygenation of arachidonic acid, an initial event in prostanoid synthesis, is accompanied by substantial oxygen radical generation. Because blockade of prostaglandin H synthase (cyclooxygenase) with indomethacin prevents GBS-induced pulmonary hypertension, we reasoned that the salutary effect of indomethacin might be associated with a reduction in the efficacy of bactericidal activity directed against GBS. To address this possibility, the distribution and viability of 111In-labeled GBS (10(8) colony forming units/kg/min i.v. for 15 min) were assessed in lungs and livers of control piglets, piglets treated with indomethacin (1 mg/kg), and piglets treated with OKY-046 (10 mg/kg), an inhibitor of thromboxane synthase that also forestalls GBS-induced pulmonary hypertension. Relative to control animals, indomethacin treatment increased pulmonary GBS uptake with no change in bacterial distribution into the liver. OKY-046 failed to influence pulmonary bacterial uptake but promoted a substantial increase in GBS depositing in the liver. In contrast to its effects on pulmonary bacterial deposition, indomethacin failed to increase lung bacterial viability relative to control animals. Indomethacin also was without effect on hepatic bacterial viability. OKY-046 failed to influence pulmonary bacterial viability but markedly augmented hepatic GBS viability to the extent that significant bacterial proliferation occurred.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594325 TI - Defective production of interleukin-6 by monocytes: a possible mechanism underlying several host defense deficiencies of neonates. AB - Several deficiencies in antibacterial defense have been described in neonates. Among those best characterized are delayed maturation of B cells into antibody producing cells, deficient T-cell maturation, and delayed cycling of hematopoietic progenitor cells after an infectious challenge. No unifying theory has been forwarded, however, to explain the concomitance of these three developmental deficiencies. IL-6, a cytokine produced primarily by monocytes and macrophages in response to stimulation by IL-1, is involved in the regulation of these three processes. Thus, we postulated that defective production of IL-6 could be a mechanism underlying these immune deficiencies of neonates. Indeed, we observed that a peak production, cells of five term neonates produced only one half as much IL-6 (14 120 +/- 2590 pg IL-6/10(6) monocytes) as those of five adults (28 940 +/- 1680 pg, p less than 0.001). Peak production was lower still by monocytes of six preterm neonates (7190 +/- 1400 pg, p less than 0.001 versus term). Production of IL-6 protein was inhibited by actinomycin D and the IL-6 mRNA content of monocytes from neonates, as assessed by competitive polymerase chain reaction, was less than that of adult monocytes. We speculate that defective IL-6 transcription might underlie some of the defects in immune regulation observed in neonates. PMID- 1594326 TI - A human milk factor inhibits binding of human immunodeficiency virus to the CD4 receptor. AB - Perinatal transmission of human immunodeficiency virus (HIV) from infected mothers to their children occurs at rates reported as 20-50%. The role of breast feeding in perinatal transmission of viral infections has not been well established. We studied 34 milk and colostral samples obtained from HIV seropositive and HIV-seronegative women to determine if they contained anti-HIV activity. We found that all the samples contained a factor that inhibited the binding of HIV epitope-specific MAb to recombinant CD4 receptor molecules. The titers of inhibitory activity ranged from 1:200 to 1:10,000 and did not differ between HIV-seropositive and HIV-seronegative mothers. This milk factor also inhibited the binding of gp120 to CD4. Neither human sera nor bovine milk exhibited appreciable inhibitory activity. Fractionation of human milk indicated that the inhibitory activity was confined to the macromolecular fraction; little activity was found in isolated milk lipids or oligosaccharides. Chromatographic procedures indicated that the active macromolecule has an isoelectric point of 9.3-9.6. The active material did not bind to concanavalin A; however, the activity was partially destroyed by chemical and enzymatic treatments that removed sulfated residues. The active material may thus be a sulfated protein, glycoprotein, mucin, or glycosaminoglycan that inhibits the binding of CD4 to HIV envelope glycoproteins. The role of this factor in the natural history of HIV infection in infants and children should be the subject of additional investigations. PMID- 1594327 TI - Immunochemical characterization of variant medium-chain acyl-CoA dehydrogenase in fibroblasts from patients with medium-chain acyl-CoA dehydrogenase deficiency. AB - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a common autosomal recessive disorder of mitochondrial fatty acid oxidation characterized by episodes of hypoketotic hypoglycemia usually beginning in the first 2 y of life. We previously showed, in pulse labeling experiments, that the biosynthesis and immediate posttranslational processing of MCAD are normal in fibroblasts from patients with MCAD deficiency. Most patients studied to date are homozygous for a point mutation (A985-G) that results in the substitution of glutamate for lysine ar residue 304 of the mature MCAD subunit. We performed immunoblot analysis of fibroblast MCAD from a total of 34 patients with MCAD deficiency, including 31 homozygous for the A985-G mutation, using a rabbit anti-rat MCAD antibody that cross-reacted specifically with human MCAD, but not with the related enzymes, short-chain and long-chain acyl-CoA dehydrogenases. All patients with the A985-G mutation lacked detectable MCAD. Pulse-chase labeling of MCAD-deficient fibroblasts with 35S-methionine demonstrated that this variant MCAD was unstable compared to controls. Taken together, these data suggest that this mutation affects the stability of MCAD protein within the mitochondrial matrix. PMID- 1594328 TI - Diagnosis of medium-chain acyl-CoA dehydrogenase deficiency in lymphocytes and liver by a gas chromatographic method: the effect of oral riboflavin supplementation. AB - The activity of medium-chain acyl-CoA dehydrogenase (MCAD) with octanoyl-CoA as a substrate was measured in human lymphocytes by a gas chromatographic technique. Phenazine methosulfate was used as the primary electron acceptor. After the addition of crotonase and subsequent hydrolysis, the reaction product 3 hydroxyoctanoic acid was quantitated by capillary gas-liquid chromatography of the trimethylsilyl derivatives. Control subjects had MCAD activities of 3.46 +/- 0.18 nmol/mg protein/min (n = 15). Five patients were investigated while receiving no therapy at all; MCAD activity ranged from 0.08 to 0.23 in four of them and was 0.65 in the fifth one. Subsequent to the long-term administration of 50-150 mg/d of riboflavin to MCAD-deficient patients (n = 11), these activities increased to an average of 0.41 in 10 patients and 2.22 in one. The activities in 15 obligate heterozygotes were 1.91 +/- 0.41 nmol/mg protein/min, thus enabling a clear distinction from controls. Neither heterozygotes nor a control responded to riboflavin. The method was also applicable to postmortem liver tissue. One patient, who had died suddenly and unexpectedly at the age of 19 mo, was correctly diagnosed as MCAD-deficient, whereas five additional children who died of the sudden infant death syndrome showed normal activities. PMID- 1594329 TI - Hereditary tyrosinemia type I: lack of correlation between clinical findings and amount of immunoreactive fumarylacetoacetase protein. AB - Immunoblot analyses with bovine fumarylacetoacetase antibodies have been performed in fibroblast extracts from 28 patients with hereditary tyrosinemia of various clinical phenotypes, in one healthy individual homozygous for a "pseudodeficiency" gene for fumarylacetoacetase, and in three tyrosinemia families in which one or both parents are compound heterozygotes for the tyrosinemia and pseudodeficiency genes. Liver extracts from two chronic patients were also investigated. None of the patients with the acute type of tyrosinemia had detectable immunoreactive protein in fibroblast extracts. Only two of seven patients with typical chronic tyrosinemia had definite immunoreactivity in fibroblasts. In liver tissue, one of the patients had cross-reactive material and the other had no immunoreactivity. Four of 13 patients with intermediate clinical findings showed immunoreactivity in fibroblasts. There was no relationship between severity of symptoms and amount of cross-reactive material in this group. The pseudodeficiency gene product gave almost no detectable immunoreactivity in fibroblasts. The results indicate that chronic tyrosinemia may be due to at least two protein variants, and immunoblotting does not classify tyrosinemia patients according to clinical findings. PMID- 1594330 TI - Early postnatal development in the rat is characterized by accumulation of highly unsaturated triacylglycerols. AB - Our objective was to determine the quantitative changes of individual triacylglycerol (TG) species in liver and carcass during early postnatal growth. Pregnant rats were killed at d 21 of pregnancy, and neonatal rats were killed at d 3 or 9 after birth. Quantitative changes in fatty acids and TG species of fetal/neonatal liver and carcass were determined using capillary gas liquid chromatography. At postnatal d 3 or 9 compared with fetal d 21, total carcass TG increased 11- to 12-fold, with nonessential fatty acids increasing 8- to 9-fold, n-6 essential fatty acids (EFA) increasing 34- to 44-fold, and n-3 EFA increasing 19- to 29-fold, respectively. Total neonatal liver TG increased 13-fold from fetal d 21 to postnatal d 3, with a 6-fold increase in non-EFA, a 34-fold increase in total n-6 EFA and a 65-fold increase in total n-3 EFA. At postnatal d 3 compared with fetal d 21, larger molecular weight liver TG classes (C56-C64) increased 68-fold, followed by lower molecular weight TG classes C40-C48 (19 fold) with only a 6-fold increase in C50-C54. In liver, highly unsaturated TG classes (C56-C64) accounted for 49% of total TG at postnatal d 3 and consisted mainly of arachidonic, docosahexaenoic, and linoleic acids accompanied by palmitic and oleic acids. During early postnatal development, TG species containing one, two, or even three 20-22 EFA may be structurally important themselves or serve as direct substrates for synthesis of phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594331 TI - Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation. AB - Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594332 TI - Intrauterine growth retardation: fetal glucose transport is diminished in lung but spared in brain. AB - "Uteroplacental insufficiency" often causes asymmetric fetal growth retardation. Glucose transporters control cell glucose utilization and thus may be critical in the control of fetal growth. We hypothesized that uteroplacental insufficiency might alter glucose transporter activity, protein, and gene expression and thereby affect discordant organ growth in small-for-gestational-age (SGA) fetuses. We performed bilateral uterine artery ligation in pregnant rats on d 19 of gestation (term-21.5 d) to cause uteroplacental insufficiency and obtained fetal brain and lung tissue on d 20. The brain mass of SGA fetuses did not differ from that of sham and normal fetuses, but lung mass was significantly diminished. Glucose transport, measured with [3H]2-deoxyglucose, was similar in glial cells and brain tissue of SGA, sham, and normal fetuses. In contrast, type II pneumocytes, lung fibroblasts, and lung tissue of SGA fetuses had significantly decreased glucose transport. The intrinsic activity of the glucose transporter (Km) was not altered in the brain or lung of SGA fetuses. Total glucose transporter protein measured by cytochalasin-B binding and glucose transporter 1 mRNA was diminished in SGA lung tissue and type II pneumocytes, but not in SGA brain tissue or glial cells. We could not detect glucose transporter 3 mRNA in significant quantity in any tissue. With uteroplacental insufficiency, glucose transport is differentially altered in lung and brain. Glucose transporter protein and gene expression are diminished in the lung and normal in the brain of SGA fetuses. These changes may contribute to fetal growth retardation and the phenomenon of "brain sparing." PMID- 1594333 TI - The effect of in utero insulin exposure on tissue iron status in fetal rats. AB - Newborn infants of diabetic mothers have serum biochemical signs of iron deficiency in cord blood directly related to elevations of cord erythropoietin and Hb concentrations. In sheep, chronic fetal hyperinsulinemia results in fetal hypoxemia, expansion of the red cell mass, and decreased iron concentrations, most likely due to increased iron utilization for Hb synthesis. To determine whether fetal insulin exposure also results in reduced tissue iron concentrations, we measured liver, skeletal muscle, small intestine, heart, and brain iron concentrations in newborn rat pups after s.c. fetal injection of insulin or diluent alone on d 19 of gestation. The fetuses of 11 pregnant rats were exteriorized, injected with 2 U neutral protamine Hagedorn insulin or diluent, replaced in utero, and delivered on d 22. To determine dose dependency, the fetuses of six pregnant rats were injected with 3 U of longer-acting protamine zinc insulin and delivered on d 21. At delivery, the insulin-treated groups had higher birth weights than the placebo-treated group, although plasma insulin concentrations were not different. The 2 U neutral protamine Hagedorn insulin-treated fetuses had significantly lower mean +/- SEM liver iron concentrations than the control fetuses (910 +/- 34 versus 1014 +/- 43 micrograms/g dry tissue weight; p less than 0.05), but had similar skeletal muscle iron concentrations. The 3 U protamine zinc insulin-treated fetuses had significantly lower liver and skeletal muscle iron concentrations compared to control and to 2 U neutral protamine Hagedorn insulin-treated fetuses (p less than 0.05). No differences in small intestine, heart, or brain iron concentrations were seen among groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594334 TI - Neonatal auditory brainstem response failure of very low birth weight infants: 8 year outcome. AB - Fifty-six very low birth weight infants (less than 1.5 kg) were followed until 8 y of age to see if predischarge auditory brainstem response (ABR) results were predictive of neurobehavioral development. The results suggest that early ABR may predict subsequent performance on measures of intelligence quotient, language, and reading. Unilateral ABR abnormalities did not appear predictive, but bilateral abnormalities did. Analysis of a variety of neonatal risk factors in conjunction with early ABR and hearing loss with respect to educational outcome was also undertaken. PMID- 1594335 TI - Transcutaneous oxygen and carbon dioxide during the first half year of life in premature and normal term infants. AB - Repetitive polysomnograms were recorded from a total of 33 infants, 19 healthy preterm infants, and 14 term controls between 40 wk postconceptional age and 6 mo of age. These nighttime recordings lasted 2-4 h, except at 52 wk in preterm infants and at 3 mo of age in term infants when an overnight 12-h recording was performed. Minute by minute values of transcutaneous PO2 (PtCO2) and transcutaneous PCO2 (PtcCO2) levels and variability during the awake state, active sleep, and quiet sleep were obtained through computer analyses of the polygraphic data. The results from preterm infants at corrected postconceptional age could not be differentiated from those of control infants. PtCO2 levels rose between 40 wk and 3 mo, and PtcCO2 levels declined. Sleep states modulated only the variability of PtcO2, not the level; in contrast, state modulation was seen in both variability and level of PtcCO2 throughout the age span studied. During sleep the number of transient declines in PtCO2 greater than 2.03 kPa (15 mm Hg) decreased with advancing age. Hypercapnic PtcCO2 values decreased with age as well, but their prevalence in healthy, young infants suggests the need for reevaluation of criteria for hypercapnia based on transcutaneous measurements. The data demonstrate that ventilatory regulation continues to undergo changes between 1 and 3 mo, the age of highest risk for sudden infant death syndrome. PMID- 1594336 TI - The effect of extracorporeal membrane oxygenation on coronary perfusion and regional blood flow distribution. AB - We studied the distribution of systemic blood flow during venoarterial extracorporeal membrane oxygenation (ECMO) in newborn lambs. We used a three compartment model that defined partitioning of blood flow to the heart, upper body (brachiocephalic trunk), and lower body (descending aorta). The method used concurrent left ventricular and arterial cannular injections of radiolabeled microspheres to calculate compartment flows and solve the system of equations that defined the partition model. Seven newborn lambs (1-8 d) were studied. A baseline microsphere injection (left ventricle) was performed and the animals were then placed on venoarterial ECMO using right carotid and jugular vein cannulation. The arterial cannula was placed 2-3.5 cm above the aortic valve. After stabilization on ECMO flow rates of 50 and 100 mL/min/kg, differently labeled microspheres were injected simultaneously into the left ventricle and arterial limb of the ECMO circuit. From the flow partition model, distribution of blood flow was calculated. We found that ECMO did not change the overall distribution of blood flow to the three compartments studied. However, blood flow from the ECMO circuit was preferentially directed to the upper body. Coronary arterial and abdominal organ blood flow was predominantly derived from the left ventricle at both ECMO flow rates. Coronary arterial blood flow did not significantly change on ECMO (253 +/- 45 mL/min/100 g at 50 mL/min/kg ECMO flow; 246 +/- 50 mL/min/100 g at 100 mL/min/kg ECMO flow) compared to baseline (186 +/- 31 mL/min/100 g).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594337 TI - The conductance volume catheter technique for measurement of left ventricular volume in young piglets. AB - The conductance catheter has been used extensively in the adult for instantaneous and continuous measurement of left ventricular volumes, but has not been validated for use in the small heart. To determine the accuracy of this technique, we simultaneously measured left ventricular volume by the conductance catheter and biplane cineangiography in nine piglets (2-5 wk of age) over a wide range of volumes experimentally altered by volume infusion, hemorrhage, inferior vena caval occlusion, or administration of phenylephrine, isoproterenol, or propranolol. We performed 110 comparisons and determined parallel conductance of contiguous structures (alpha Vc) for each comparison using the saline technique. End-systole and end-diastole volumes were estimated by angiography using Simpson's rule. Raw and alpha Vc-corrected conductance volumes were compared to simultaneously obtained angiographic volumes by multiple regression analyses, using dummy variable coding for the effects of the interanimal variability and the phase of the cardiac cycle. Raw conductance volumes correlated highly with the cineangiographic volumes (r = 0.97), and the coefficient of angiographic volumes was near identity (1.11 +/- 0.04). The phase of the cardiac cycle did not have a significant effect. However, alpha Vc-corrected conductance volumes correlated less (well (r = 0.85), probably related to the fact that estimated alpha Vc was found to vary with ventricular volume. Thus, the conductance catheter affords a very accurate technique for measuring instantaneous changes in ventricular volume in the small heart, although correction to absolute volumes using the saline technique for estimation of alpha Vc may induce some inaccuracy. PMID- 1594338 TI - Painful defecation and fecal soiling in children. AB - Fecal soiling is a common complaint among school-age children. The fecal soiling is often accompanied by chronic constipation and so-called "idiopathic," "functional," or "psychogenic" megacolon, the cause of which is undetermined. The records of all children presenting to a pediatric gastroenterology clinic between 1981 and 1990 with difficult defecation were reviewed to determine the incidence of painful defecation and its relationship to chronic impaction and fecal soiling. There were 227 children; 74 were younger than 36 months of age and 153 were older than 36 months. Of the younger children, 86% presented with pain, 71% with impaction, and 97% with severe withholding. The younger children had painful defecation for a mean of 14 +/- 9 (SD) months before presentation. Of the older children, 85% presented with fecal soiling, 57% with pain, and 73% with fecal impaction, and 96% exhibited withholding; the older children had difficult defecation for a mean of 56 +/- 42 months before presentation. Sixty-three percent of the children presenting with fecal soiling had a history of painful defecation beginning before 36 months of age. Painful defecation frequently precedes chronic fecal impaction and fecal soiling in American children. Early, effective treatment of painful defecation in infancy might reduce the incidence of chronic fecal impaction and fecal soiling in school-age children. PMID- 1594339 TI - Prenatal exposure to heavy metals: effect on childhood cognitive skills and health status. AB - Prenatal exposure to seven heavy metals (cadmium, chromium, cobalt, lead, mercury, nickel, and silver) was determined for amniotic fluid taken from 92 pregnant women undergoing amniocentesis at approximately 16 to 18 weeks' gestation. Follow-up assessment of their children's cognitive skills and health status was conducted when the children were approximately 3 years of age. The presence of these metals co-occurred in amniotic fluid. A prenatal toxic risk score was derived which was a weighted score reflecting the presence of the various metals in amniotic fluid. The toxic risk score was negatively related to performance on the McCarthy Scales of Children's Abilities and positively related to the number of child illnesses reported. These results suggest the need for further prospective research on the adverse effects of prenatal exposure to various metals in combination. PMID- 1594340 TI - Perinatal manifestations of maternal yellow nail syndrome. AB - A term female firstborn infant had unexplained nonimmune fetal hydrops and recurrent left chylothorax at 4 weeks of age. A few months before conception, her mother had had acute dystrophic nail changes and is being treated for recurrent sinusitis, bronchiectasis, and a deficiency of serum IgG2. We suggest that they both suffer from a dominantly inherited congenital lymphedema syndrome known as 'yellow nail dystrophy.' Prenatal manifestation of this disorder has not been reported previously. The child's anthropometric and neurological development was normal at 1 year of age, whereas mild ankle edema and marbling of the skin of the limbs were salient clinical findings. Inherited lymphedema leading to nonimmune fetal hydrops also has been recognized in chromosomal disorders, Noonan's syndrome, multiple pterygium syndrome, pulmonary lymphangiectasis, and mixed vessel lymphatic dysfunction. Indicators of parental lymphedema are not on record in those instances. PMID- 1594341 TI - Immunization opportunities missed among urban poor children. AB - Low immunization rates among US preschool children suggest a need for improved immunization practices. Immunization and encounter records were reviewed to ascertain immunization rates and missed opportunities for vaccine administration among 515 preschool children who were active patients at a hospital-based primary care center serving lower socioeconomic status families in Rochester, NY. The point prevalence at a mean age of 4.4 years for lack of one or more recommended immunizations was 27%; 7% were missing measles-mumps-rubella, 18% were missing Haemophilus influenzae type b, 8% were missing two or more diphtheria-tetanus pertussis, and 4% were missing two or more oral poliovirus immunizations. A visit was counted as a missed opportunity if an immunization was due but not given. Over the period from birth through age 36 months, 422 (82%) of children missed at least one immunization opportunity. For these 422 children, there was a mean of 7.2 missed opportunities per child. Although 64% of missed opportunities occurred at an acute illness visit, 36% occurred at well-child, administrative, follow-up, or chronic illness visits. Review of 200 medical records randomly selected from all opportunities at acute illness visits found no contraindication in 63% (50% nonfebrile infectious disease, 13% minor noninfectious problems). Findings for random samples of 100 missed diphtheria-tetanus-pertussis opportunities for children aged 2 to 6 months and 100 missed measles-mumps-rubella opportunities for children 15 to 24 months were similar to findings for the sample of all acute illness visits. Emergency department visits, where immunization records were not readily available, accounted for 18% of missed opportunities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594342 TI - Standard definitions for childhood injury research: excerpts of a conference report. AB - As awareness of the huge human and other costs of injury has grown, research has expanded. There has not been any standard set of terminology for use in this research. As a result, research and surveillance data are too often difficult to interpret and compare. To overcome this impediment to gains in needed knowledge about childhood injuries, a conference was held in 1989 by the National Institute of Child Health and Human Development to develop a set of standard definitions. The full conference report is available from the US Government Printing Office. This report presents excerpts, emphasizing those--core--variables likely to be of use to the largest number of investigators. The conference recommendations presented address cross-cutting factors (age, race/ethnicity, location, socioeconomic status, and biopsychosocial development), effect modifiers (exposure, medical risk factors, substance abuse, time, injury severity, and social risk factors), and specific injuries (motor vehicle injuries, central nervous system injuries, falls, fire/burns, drowning, and violence). It is expected that childhood injury investigators will strive to meet the recommendations of this conference and that use of these definitions will lead to improvements in research and, ultimately, to revision of the definitions. PMID- 1594343 TI - Growth of breast-fed and formula-fed infants from 0 to 18 months: the DARLING Study. AB - Anthropometric data were collected monthly from birth to 18 months as part of the Davis Area Research on Lactation, Infant Nutrition and Growth study, which followed infants who were either breast-fed or formula-fed during the first 12 months. The two cohorts were matched for parental socioeconomic status, education, ethnic group, and anthropometric characteristics and for infant sex and birth weight, and neither group was given solid foods before 4 months. While mean weight of formula-fed infants remained at or above the National Center for Health Statistics median throughout the first 18 months, mean weight of breast fed infants dropped below the median beginning at 6 to 8 months and was significantly lower than that of the formula-fed group between 6 and 18 months. In contrast, length and head circumference values were similar between groups. Weight-for-length z scores were significantly different between 4 and 18 months, suggesting that breast-fed infants were leaner. The groups had similar weight gain during the first 3 months, but breast-fed infants gained less rapidly during the remainder of the first year: cumulative weight gain in the first 12 months was 0.65 kg less in the breast-fed group. Length gain was similar between groups. These results indicate that weight patterns of breast-fed infants, even in a population of high socioeconomic status, differ from current reference data and from those of formula-fed infants. Thus, new growth charts based on breast-fed infants are needed. PMID- 1594344 TI - Utility of an end-tidal carbon dioxide detector during stabilization and transport of critically ill children. AB - Critically ill children often require endotracheal intubation prior to transport to a medical center. Correct endotracheal tube placement and maintenance during transport are essential. The utility of a portable colorimetric end-tidal CO2 detector during transport of critically ill children was evaluated. Fifty-eight children with spontaneous circulation (aged 1 day to 12 years, weight 0.9 to 26 kg) who underwent 59 intubations during transport by ground (n = 31) or air (n = 27) were studied. Tube position was confirmed by physical examination, arterial blood gas values, or arterial oxygen saturation, and sometimes by chest radiography. The detector was attached and readings were obtained after intubation; readings were repeated if endotracheal tube position was rechecked during transport. Fifty-seven of 58 tracheal positions and the 1 esophageal tube position were correctly identified. One false-negative result occurred in a severely hypocarbic 900-g premature newborn. On each occasion that the detector was used en route, the endotracheal tube position was correctly identified. It is concluded that the end-tidal CO2 detector is a useful tool for confirming endotracheal tube position during transport of critically ill children weighing more than 2 kg who are not in cardiopulmonary arrest. PMID- 1594345 TI - Babesiosis: an underdiagnosed disease of children. AB - Babesiosis is a malaria-like illness caused by the intraerythrocytic parasite Babesia microti and is transmitted by the same tick that transmits Borrelia burgdorferi, the causative agent of Lyme disease. Babesiosis is well recognized in adult residents of southern New England and New York but has been described in only five children. To determine whether children are infected with B microti less often than are adults, a prospective serosurvey was carried out on Block Island, RI, where babesiosis is endemic. Randomly recruited subjects completed a questionnaire and provided a blood sample. Antibodies against B microti and B burgdorferi were measured using a standard indirect immunofluorescence assay and enzyme-linked immunosorbent assay, respectively. Of 574 subjects, 9% tested positive for B microti, including 12% of the 52 children (7 months through 16 years) and 8% of the 522 adults (not significant, P less than .6). Although babesiosis had not been diagnosed in any of the Babesia-seropositive subjects, 25% of the children and 20% of the adults reported symptoms compatible with this infection during the previous year. Of the 6 children and 45 adults seropositive for B burgdorferi, 17% and 14%, respectively, were also seropositive for B microti. It is concluded that children are infected with B microti no less frequently than are adults and that this infection is underdiagnosed in all age groups. Physicians who practice where Lyme disease is endemic should become familiar with the clinical presentation and diagnosis of babesiosis, both in adults and children. PMID- 1594346 TI - Birth spacing and child health in urban Brazilian children. AB - The associations between birth interval and a range of child health outcomes were examined in a population-based cohort of approximately 3500 urban Brazilian children. The effects of several socioeconomic and maternal confounding factors were controlled for in the analyses. Children born after shorter birth intervals (less than 18 and 18 through 23 months) were disadvantaged with respect to most of the health outcomes when compared with children born after intermediate birth intervals (24 through 35, 36 through 47, and 48 through 71 months). Effects were particularly marked for birth weight, postneonatal mortality, and anthropometric status at mean age 19 months. Children born after a long birth interval (greater than 71 months) also showed some disadvantage for birth weight, perinatal mortality, and infant mortality. However, this group experienced lower risks of hospitalizations during the first 19 months of life and better anthropometric status at mean age 19 months. This study provides data that are scarce from such settings and contributes to the quantification of associations between birth spacing and child health. This information is important in the planning of appropriate intervention strategies. PMID- 1594347 TI - Effect of recipient's race on pediatric renal allograft survival: a single-center study. AB - One hundred twenty-seven children (83 males, 44 females, 86 white, 41 nonwhite; mean age 12.1 years) who received 160 renal transplants between 1980 and 1989 were retrospectively studied. Variables such as age, sex, primary diagnosis, type, HLA-DR mismatching, and repeated transplants were compared between races and found not to be significant. However, HLA-A and -B cadaveric-graft mismatching, which was equivalent between whites and nonwhites prior to 1985 (pre cyclosporine A era), has significantly favored whites (49% with 0 to 2 HLA-A and B mismatch vs 16% in nonwhites) since 1985 (P less than .05), and a significantly higher proportion of nonwhite patients (59%) were receiving medical assistance (P less than .0001). Graft survival was evaluated with significantly poorer results in nonwhites as compared to whites (P less than .05). Although no difference was found between white and nonwhite cadaveric-graft survival before 1985, nonwhites had significantly worse graft survival since 1985 (72% vs 59% for 1 year and 61% vs 24% for 3 years in whites and nonwhites, respectively; P less than .05). Subpopulations such as nonwhite adolescents, nonwhite females, nonwhites with repeated transplants, and all low socioeconomic patients were identified as high risk children with poor long-term survival. It is concluded that secondary to poorer matching since 1985 there has been decreased graft survival in nonwhites despite cyclosporine A. Attempts to improve matching and attention to high-risk groups are needed for equivalent survival. PMID- 1594348 TI - Standards for selected anthropometric measurements in males with the fragile X syndrome. AB - Standards (95th, 50th, and 5th percentiles) in fragile X syndrome for weight, height, head circumference, ear length, and testicular volume are reported. For comparison with fragile X syndrome standardized curves, normal control data from the literature were similarly plotted and curves produced. These standards reflect the physical parameters that are frequently abnormal in males with the fragile X syndrome and should be useful in the medical management of patients with this syndrome. The standards may also be used to help identify those individuals, particularly the younger males, for chromosome studies to confirm the clinical impression of the fragile X syndrome. PMID- 1594349 TI - Bucket-related drownings in the United States, 1984 through 1990. AB - The purpose of the study is to document the incidence of bucket-related drowning in the United States and to identify factors associated with this type of submersion injury. Analysis of Consumer Product Safety Commission data revealed 160 bucket-related drownings for the years 1984 through 1989, representing a mortality rate of 0.367 per 100,000 persons (younger than 2 years old) per year in the United States. Eighty-eight percent of bucket drownings occurred in toddlers aged 7 to 15 months old. Black children were six times more likely to drown in a bucket than white children of similar age (P less than .0001). Male toddlers were at significantly greater risk than females (P less than .01). A seasonal trend present in the data indicated that infants are more likely to drown in warmer than in colder months (P less than .01). States with the highest rates of bucket drowning were Vermont (2.1/100,000), Arizona (1.5/100,000), and Illinois (1.0/100,000). Through passive and active educational strategies, perhaps this fatal home injury can be prevented. PMID- 1594350 TI - Renal tubular acidosis in children treated with trimethoprim-sulfamethoxazole during therapy for acute lymphoid leukemia. AB - The antibiotics trimethoprim (TMP) and sulfamethoxazole (SMZ), when used in combination, can cause metabolic acidosis, renal bicarbonate wasting, and growth failure. Retrospective review of repeated random serum chemistries from 10 children receiving TMP-SMZ and maintenance chemotherapy for acute lymphoid leukemia revealed low serum bicarbonate (P = .0002) and elevated serum chloride (P less than .0005) concentrations. These values normalized after all medications were discontinued. Prospective study of 8 children receiving TMP-SMZ and chemotherapy for acute lymphoid leukemia revealed lower serum bicarbonate concentrations and higher urine pH following a dose of TMP-SMZ than paired values obtained more than 3 days after a dose. Four children (50%) met serum bicarbonate and urinary pH criteria for the diagnosis of renal tubular acidosis soon after a dose of TMP-SMZ. The occurrence of TMP-SMZ-induced renal tubular acidosis has implications for the acid-base balance of children receiving TMP-SMZ on a long term basis. PMID- 1594351 TI - Cognitive-behavioral pain management in children with juvenile rheumatoid arthritis. AB - Decreasing chronic joint pain is a major goal in the management of juvenile rheumatoid arthritis. Cognitive-behavioral self-regulatory techniques were taught to children with juvenile rheumatoid arthritis to reduce musculoskeletal pain intensity and to facilitate better adaptive functioning. Subjects were 13 children between the ages of 4.5 and 16.9 years who had pauciarticular or systemic onset juvenile rheumatoid arthritis. Baseline data included an initial comprehensive assessment of pain, disease activity, and level of functional disability, as well as pain intensity ratings gathered over a 4-week period. Subjects were seen for eight individual sessions in which self-regulatory techniques (progressive muscle relaxation, guided imagery, meditative breathing) were taught, and parents were seen for two sessions in which key aspects of behavioral pain management techniques were reviewed. Results indicated that these techniques led to substantial reduction of pain intensity, which generalized to outside the clinic setting. Six- and 12-month follow-up data showed consistent decreases in pain as well as improved adaptive functioning. The data suggest that cognitive-behavioral interventions for pain are an effective adjunct to standard pharmacologic interventions for pain in patients with juvenile rheumatoid arthritis. PMID- 1594352 TI - 3-Methylglutaconic aciduria: a new variant. AB - 3-Methylglutaconic aciduria has been described in two distinct syndromes. In one there was deficient 3-methylglutaconyl coenzyme A hydratase in fibroblast extracts where the only clinical manifestation was retarded speech development. In the second syndrome, the enzyme activity was normal but prominent neurological deterioration was noted. We describe two siblings with 3-methylglutaconic aciduria with normal enzyme activity who had choreoathetoid movements, optic atrophy, and mild developmental delay. The boy demonstrated developmental improvement in his second year of life, and his sister developed well, with normal school performance. These patients represent a new clinical variant of the second syndrome with a relatively favorable prognosis. PMID- 1594353 TI - Humor in the pediatric emergency department: a 20-year retrospective. AB - Humorous events often take place in pediatric emergency departments without being recorded. A written account of amusing situations occurring in an emergency department has been compiled over 20 years by personnel at a large urban children's hospital. Data from this reference were analyzed for humorous content and presented in the following categories: most interesting chief complaints, suspicious sounding chief complaints, favorite telephone inquiries, and illustrative cases. This study demonstrates that an emergency department may be a fertile source of medical humor. Recognition of these statements and events helps to relieve the stress of medical training and emergency department work. PMID- 1594354 TI - Injury illiteracy. PMID- 1594355 TI - Zinc deficiency in a full-term breast-fed infant: unusual presentation. PMID- 1594356 TI - Eosinophilic pustular folliculitis. AB - Eosinophilic pustular folliculitis is a cutaneous disorder that consists of recurrent crops of pruritic, sterile, papulopustules in a follicular distribution. In pediatric patients, EPF presents primarily in the scalp and is confused with several other more common dermatoses in children. The diagnosis of EPF rests on its inclusion in the differential diagnosis of papulopustular disorders, the recognition of the clinical presentation, and the presence of an eosinophilic infiltrate on biopsy. Treatment with midpotency topical corticosteroids has thus far met with modest success. This is the first report on EPF in the pediatric literature. As pediatricians become more aware of EPF as a distinct clinical entity and as our clinical experience and insight into the pathogenesis of EPF grows, perhaps more effective treatment modalities will be devised. PMID- 1594357 TI - American Academy of Pediatrics Committee on Nutrition: The use of whole cow's milk in infancy. AB - The pediatrician is faced with a difficult challenge in providing recommendations for optimal nutrition in older infants. Because the milk (or formula) portion of the diet represents 35% to 100% of total daily calories and because WCM and breast milk or infant formula differ markedly in composition, the selection of a milk or formula has a great impact on nutrient intake. Infants fed WCM have low intakes of iron, linoleic acid, and vitamin E, and excessive intakes of sodium, potassium, and protein, illustrating the poor nutritional compatibility of solid foods and WCM. These nutrient intakes are not optimal and may result in altered nutritional status, with the most dramatic effect on iron status. Infants fed iron-fortified formula or breast milk for the first 12 months of life generally maintain normal iron status. No studies have concluded that the introduction of WCM into the diet at 6 months of age produces adequate iron status in later infancy; however, recent studies have demonstrated that iron status is significantly impaired when WCM is introduced into the diet of 6-month-old infants. Data from studies abroad of highly iron-deficient infant populations suggest that infants fed partially modified milk formulas with supplemental iron in a highly bioavailable form (ferrous sulfate) may maintain adequate iron status. However, these studies do not address the overall nutritional adequacy of the infant's diet. Such formulas have not been studied in the United States. Optimal nutrition of the infant involves selecting the appropriate milk source and eventually introducing infant solid foods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594358 TI - American Academy of Pediatrics Committee on Drugs: Guidelines for monitoring and management of pediatric patients during and after sedation for diagnostic and therapeutic procedures. PMID- 1594359 TI - American Academy of Pediatrics Committee on Bioethics: Infants with anencephaly as organ sources: ethical considerations. PMID- 1594360 TI - Endothelin and hemolytic uremic syndrome. PMID- 1594361 TI - Parents and politics. PMID- 1594362 TI - Talented students. PMID- 1594363 TI - Neurotoxicity of lorazepam in a premature infant. PMID- 1594364 TI - Strategies to reduce hyperkalemia-induced cardiac arrhythmias in premature infants and newborns. PMID- 1594365 TI - Comparison of pediatric poisoning hazards: an analysis of 3.8 million exposure incidents. A report from the American Association of Poison Control Centers. AB - This analysis of life-threatening and fatal pediatric poisonings was conducted to aid poison prevention educational efforts, guide product reformulations and aversive agent use, reassess over-the-counter status for selected pharmaceuticals, and identify research areas for clinical advances in the treatment of pediatric poisonings. A hazard factor was devised to assess more objectively the pediatric poisoning hazard posed by pharmaceutical and nonpharmaceutical products. By considering the frequency and extent of injury following actual exposures, the hazard factor reflects more than the acute toxicity of individual ingredients and is also influenced by such variables as packaging, accessibility, availability (as a reflection of marketing), formulations, and closure types. Of the 3,810,405 exposures involving children younger than 6 years of age reported to poison centers in 1985 through 1989, 2117 patients experienced a major outcome (life-threatening effect or residual disability) and an additional 111 fatalities occurred. The three most commonly implicated substance categories, accounting for 30.4% of reported exposures, include cosmetics and personal care products, cleaning substances, and plants. All had low hazard factors, with significant hazards being limited to a small number of products identified herein. Thus this analysis of hazard factors demonstrates that frequent exposure does not imply toxicity. Iron supplements were the single most frequent cause of pediatric unintentional ingestion fatalities, accounting for 30.2% of reported pediatric pharmaceutical unintentional ingestion fatalities reported over an 8-year period. Antidepressants, cardiovascular medications, and methyl salicylate follow in frequency of pediatric pharmaceutical deaths. Hydrocarbons (including five lamp oil deaths) and pesticides were each implicated in 12 pediatric ingestion fatalities during the 8-year period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594367 TI - Peripheral intravenous catheter complications in critically ill children: a prospective study. AB - Six hundred fifty-four peripheral Teflon catheters in 303 pediatric intensive care unit patients were examined to determine complication rates and associated risk factors. Phlebitis, extravasation, and bacterial colonization occurred at rates of 13%, 28%, and 11%, respectively. Logistic regression of factors that increased phlebitis risk revealed infusion of hyperalimentation (odds ratio 2.9) or lorazepam (odds ratio 2.2) and catheter location (odds ratio 2.9) as the most important determinants of phlebitis risk. Age (less than or equal to 1 year, odds ratio 2.0), catheter time in situ (less than or equal to 72 hours, odds ratio 2.1), and infusion of antiepileptics (odds ratio 2.1) were the most important determinants of extravasation. Catheters were colonized most frequently with coagulase-negative Staphylococcus (51/54). Sepsis attributable to catheter colonization occurred in 1 patient. Duration of catheter placement (greater than or equal to 144 hours, odds ratio 5.8) was an important determinant of catheter colonization. Colonization risk increased from 11% in catheters that were in situ for 48 to 144 hours to 34% for catheters that were in for longer than 144 hours. Infusion of diazepam (odds ratio 11.0) or lipid emulsions (odds ratio 2.5) and age (less than or equal to 1 year, odds ratio 2.2) were also important determinants of colonization risk. Replacing catheters in critically ill children every 72 hours would not decrease phlebitis, bacterial colonization, or catheter induced sepsis and could increase extravasation risk. Catheters can be safely maintained with adequate monitoring for up to 144 hours in critically ill children. PMID- 1594366 TI - Clinical and cost-effectiveness of outpatient strategies for management of febrile infants. AB - Young infants with fever are at risk for serious bacterial infection, but no consensus exists on the optimal approach to diagnosis and treatment. Although the traditional recommendation is always to perform all sepsis tests, including lumbar puncture, and administer intravenous (IV) antibiotics until culture results are negative, recent studies suggest administering intramuscular (IM) ceftriaxone with outpatient follow-up or using laboratory and clinical data to exclude low-risk patients from hospitalization, further testing, and antibiotic treatment. A decision analysis model was used to evaluate six strategies for the diagnosis and treatment of infants aged 28 to 90 days with temperature greater than or equal to 38.0 degrees C. Data from the literature, data from a 1991 study of 503 febrile infants, and direct, short-term costs from the Children's Hospital of Philadelphia were used as model inputs. The model was run for a hypothetical cohort of 100,000 febrile infants who did not require admission for focal infection or for other reasons that clearly necessitated admission. The model included six strategies: (1) no intervention; (2) all sepsis tests (lumbar puncture, blood culture, urine culture, white blood cell count, and urinalysis) followed by hospitalization and IV antibiotics for all infants; (3) all sepsis tests followed by IM ceftriaxone and outpatient management for most infants; (4) blood and urine cultures with white blood cell count and urinalysis followed by either lumbar puncture and IV antibiotics for high-risk infants or outpatient management without antibiotics for low-risk infants; (5) white blood cell count and urinalysis followed by either lumbar puncture, blood and urine cultures, and IV antibiotics for high-risk infants or outpatient management without antibiotics for low risk infants; and (6) clinical judgment followed by either all sepsis tests and IV antibiotics for high-risk infants or outpatient management without antibiotics for low-risk infants. The two "all sepsis tests" strategies prevented the most cases of death or neurologic impairment, 78% (when IV antibiotics were used) and 76% (when IM ceftriaxone was used) of all potential cases. The most cost-effective strategy was to use all sepsis tests followed by IM ceftriaxone for all patients without meningitis, at an incremental cost of only $3900 per sequela prevented relative to no intervention. Strategies under which only those patients selected as high-risk by laboratory criteria received antibiotic treatment were less effective but incurred lower rates of antibiotic complications. Clinical judgment alone was the least clinically effective and the second least cost-effective strategy.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1594368 TI - Respiratory health and lung function in 8-year-old children of very low birth weight: a cohort study. AB - In comparison with a cohort of normal birth weight children, those of very low birth weight (less than 1501 g birth weight) had more wheezing illnesses and hospital readmissions for respiratory problems in the first 2 years of life; from 2 years to 8 years of age respiratory health was unrelated to birth weight. Lung function measurements at 8 years of age in very low birth weight children were similar to expected values; few children had severely abnormal lung function. On univariate analyses, forced vital capacity (FVC) and forced expired volume in 1 second (FEV1), but not flow rates, were lower in children who had survived bronchopulmonary dysplasia. However, the univariate analyses were misleading, because bronchopulmonary dysplasia occurred more frequently with lower birth weight, and lower birth weight in turn was strongly related to reduced FVC and FEV1. After adjusting for birth weight and other potential confounding variables, FVC and FEV1 were unrelated to bronchopulmonary dysplasia, and to neonatal ventilation. Flow rates were largely uninfluenced by perinatal events, but were reduced in children with asthma or recurrent bronchitis at 8 years of age. Passive smoking was unrelated to lung function at 8 years of age. However, the effects of passive or active smoking, or perinatal events, on respiratory function or health beyond 8 years of age in very low birth weight survivors remain to be determined. PMID- 1594369 TI - Parents' behavior and attitudes toward screening children for high serum cholesterol levels. AB - The American Academy of Pediatrics, concerned that pediatric cholesterol screening may lead to mislabeling and overly restrictive diets, stresses laboratory confirmation and nutritional follow-up for children with elevated cholesterol levels. Parents' behavior and attitudes toward screening children for high cholesterol were studied. During an 8-week period in summer of 1989 all children 2 through 15 years of age seen for well-child examinations at a community pediatric group practice were offered cholesterol screening by finger stick method. Most parents were well-educated and white. Of 439 children screened, 134 (31%) had cholesterol levels above the recommended cutoff point of 175 mg/dL (75th percentile). Only 63 children returned for confirmatory lipid panels; parents of children who did not return were interviewed. Reasons for noncompliance included "not sure test machine was accurate" (67%); "child too traumatized by finger stick" (47%); and "will try low-cholesterol diet before recheck" (40%). A third of these parents believed that confirmation of an elevated cholesterol level "would make the child worry too much." Only 29% of these parents talked with a dietician. In this middle-class, well-educated population, a large proportion of children had elevated screening cholesterol values, but few complied with American Academy of Pediatrics guidelines. As a result, many children may be mislabeled as hypercholesterolemic and may not benefit from screening. PMID- 1594370 TI - Interdisciplinary evaluations of alleged sexual abuse cases. AB - Children who are alleged to have been sexually abused often go through gruelling interrogations to relate their experiences to adults and, even then, most are not viewed as reliable sources of information. The Victim Sensitive Interviewing Program (VSIP) was initiated to decrease the number of interviews endured by a child who allegedly had been sexually abused. The program brought together the disciplines involved in the evaluation of these cases: hospital-based social worker and pediatrician, state child protective agency worker, police, and assistant state's attorney. This team established a protocol for an investigative interview to be conducted by a team member. Pre-VSIP sexual abuse evaluations from 1985 and 1986 (38) were compared with VSIP evaluations (226) from 1987 and 1988. There was no significant difference between the two groups in relation to gender or age of victim, physical symptoms, physical findings, sexually transmitted diseases present, age of perpetrator, or length of stay in hospital. However, there were significant differences between the two groups in (1) number of interviews, 11% pre-VSIP vs 79% VSIP receiving only one interview (P less than .001); (2) number of interviewers, 24% pre-VSIP vs 88% VSIP were interviewed by only one interviewer (P less than .001); (3) indicated cases of sexual abuse, 68% pre-VSIP vs 88% VSIP (P less than .006); (4) identification of the perpetrator, 71% pre-VSIP vs 85% VSIP (P less than .035); and (5) charges pressed if perpetrator identified, 33% pre-VSIP vs 60% VSIP (P less than .010). It is concluded that interdisciplinary evaluations of alleged sexual abuse in children not only decreased the number of interviews a child must undergo but also increased the likelihood of indicated cases, identification of the perpetrator, and charges being pressed. Therefore, it is strongly recommended that interdisciplinary teams be formed to assess alleged sexual abuse in children. PMID- 1594371 TI - Exposure to Toxoplasma gondii and cat ownership in Nova Scotia. AB - In this survey, 998 children and adolescents between 7 months and 17 years of age who attended a hospital diagnostic center in the city of Halifax, Nova Scotia, for routine evaluation were tested for Toxoplasma gondii antibody. The 5.2% prevalence rate of antibody for children living in the outlying rural areas was significantly higher than the 1.1% rate among the urban children (P = .0006). Seroprevalence increased with age for both rural and urban children. Cat ownership was associated with antibodies to Toxoplasma among rural children but not urban children. Rural children who lived in a house with more than one cat were two times more likely to be infected than children who had one cat and three times more likely to be infected than children with no cats. The geometric mean titer was also significantly higher among the rural children with more than one cat, 1:152, than rural children with one or no cats, 1:63 (P = .02). In light of these findings for children and adolescents, the association of Toxoplasma infection with cat ownership needs to be thoroughly evaluated among pregnant women in rural areas. PMID- 1594372 TI - Pediatric equestrian injuries. AB - Using data from four sources, horse-related injuries are summarized for persons younger than 25 years of age. Head injury caused 57% of deaths. The upper extremity was the most common area injured, with the next most frequent areas the lower extremity (National Park Service data) and the head (United States Pony Clubs [USPC] data). Injured females outnumbered injured males and had a greater percentage of participants injured (USPC data). Injuries occurred at home in 41% (National Electronic Injury Surveillance System data). USPC figures suggest that greater knowledge may reduce the severity of horse-related injuries. Previous horse-related injury had occurred in 1 of 4 of those injured (USPC data). One third of accidents occurred during lessons (USPC data). Riding instructors should be certified by a recognized organization, and parents should evaluate an instructor's personal riding and their safety records with students. The pediatrician's role should be in counseling parents with children who ride and in offering recommendations for safety to governing boards of youth horse activities. PMID- 1594373 TI - Pulmonary disease with hemorrhage in Henoch-Schoenlein purpura. AB - Henoch-Schonlein purpura is a common vasculitic syndrome of childhood. Pulmonary hemorrhage is a rare complication, which resulted in death in three of four previously reported cases. We report concerning four additional patients with Henoch-Schonlein purpura and pulmonary hemorrhage. Three survived the episode. Aggressive and supportive care may improve survival. PMID- 1594374 TI - Long-term follow-up of 12 patients with the late-onset variant of argininosuccinic acid lyase deficiency: no impairment of intellectual and psychomotor development during therapy. AB - To date, two variants of argininosuccinic acid lyase deficiency, the second most common enzymatic defect of the urea cycle, have been described. Most of the previous studies reported on outcomes involving neurological and intellectual impairment in affected children. This study is the first to demonstrate that the physical and mental development of such children can be normal and adequate for their age if they are treated with a low-protein diet and/or arginine supplements. Since 1973, 12 Austrian children suffering from argininosuccinic acid lyase deficiency have been detected in the Austrian Neonates Screening Program and could have been followed up. After confirmation of diagnosis, all the children were administered a daily arginine supplement (3 to 4 mmol/kg per day) in conjunction with either a normal diet or a special diet in which protein intake was restricted to 1.2 to 1.5 g/kg per day. Routine checks, including physical examination, determination of biochemical parameters, and IQ tests, were performed so the further development of these 12 patients with respect to treatment could be observed. It can be concluded that early treatment of partial argininosuccinic acid lyase deficiency results in normal intellectual and psychomotor development. PMID- 1594375 TI - Delayed diagnosis of pediatric cervical spine injury. AB - We report on nine patients in whom there were delays in establishing a diagnosis of cervical spine injury and discuss the causes that contributed to the delays, their clinical significance, and whether or not asymptomatic injury occurs. PMID- 1594376 TI - Lethal toxic encephalopathy due to childhood shigellosis in a developed country. AB - Shigellosis results in considerable morbidity in endemic areas, but mortality is rare in developed countries. All pediatric deaths (n = 15) in Israel following shigellosis in the past 10 years were reviewed. The patients' ages ranged from 5 months to 11 years; there were eight boys and seven girls. Three were institutionalized mentally retarded patients, 11 were healthy children. Twelve had definite clinical signs of brain death within 48 hours of onset of disease. Cause of death in all patients was consistent with toxic encephalopathy. No other systemic complication was implicated as the cause of death except for one case consistent with a "Reye-like" syndrome. Shigella species were as follows: 8 flexneri, 4 sonnei, 1 dysenteriae, and 2 were not identified. Case-control study of these patients vs surviving, hospitalized patients with shigellosis showed similar severity of fever, diarrhea, vomiting, and dehydration and similar incidence of convulsions. Headache was a prominent feature of patients who died; 5 of 7 verbal patients complained of this symptom as opposed to 2 of 20 in the control group (P less than .01). There were no significant differences in the hematological and biochemical profile (except for an increased incidence of hyponatremia in the study group), pattern of shigella species, or antibiotic sensitivity. These findings indicate that mortality from shigellosis in a developed country is due primarily to the toxic encephalopathy syndrome. PMID- 1594377 TI - Effects of in utero cocaine exposure on newborn acoustical cry characteristics. AB - As part of a large, multicenter study of newborn cry analysis and Sudden Infant Death Syndrome, we examined the effects of in utero cocaine exposure on ten acoustical cry characteristics. Newborn cry recording and medical record review was performed for 23,948 newborns. Cocaine use during pregnancy (determined by record review) was identified in 438 (1.8%) women (310 by self-report only; 128 newborns also had positive urine assay). A demographically similar group of 373 newborns, selected from the 23,510 newborns without known cocaine exposure, made up the comparison group. Cry analysis was technically possible for 768 recordings: 404 cocaine-exposed and 364 non-exposed controls. Comparison of cocaine-exposed vs control newborns, after adjustment for potential confounding variables, found significant differences including: fewer cry utterances (P = .001), more short cries (P = .02), and less crying in the hyperphonation mode (P = .01), for the cocaine-exposed neonates. As reported in other studies, cocaine exposed newborns also were significantly lower in birth weight, length, and head circumference. Newborns who had positive urine tests for cocaine suffered the greatest effects on both cry and growth parameters. These findings suggest a pattern of underaroused neurobehavioral function and are consistent with the emerging picture of the adverse neurobehavioral effects of cocaine. Developmental outcome studies are in progress to determine if acoustical analysis of the newborn cry can be used to identify cocaine-exposed newborns who are at highest risk for poor outcome. PMID- 1594378 TI - Standardized instructions: do they improve communication of discharge information from the emergency department? AB - To determine whether standardized instructions enhance communication of discharge information, we provided 197 parents of children in whom otitis media was diagnosed with one of three types of instruction at the time of discharge from a pediatric emergency department: (1) instruction by individual housestaff and medical students after consultation with an attending physician (control group); (2) standardized verbal instructions given by housestaff and students trained in their use (verbal group); or (3) the same instructions given to the verbal group, together with a type-written copy of the information to take home (verbal + written group). Prior to leaving the emergency department and, again, by phone, 1 and 3 days later, parents were questioned concerning the prescribed medication's name, dose, frequency, and duration of administration (medication data), three signs of improvement, and eight signs indicating the need for medical advice (worrisome signs). The mean percentage of correct responses per parent in each group was computed for each information category. Both at exit interview and at follow-up, parents receiving either form of standardized instructions showed significantly greater knowledge of information related to their child's illness than did controls. Information regarding medication data was more likely to be communicated to parents in all groups than were signs of improvement or worrisome signs. The addition of written instructions to standardized verbal instructions did not improve parental recall of discharge information. PMID- 1594379 TI - Bicycle helmet use among Maryland children: effect of legislation and education. AB - Although bicycle helmets are effective in preventing head injuries, use of helmets among children remains infrequent. In response to the bicycling deaths of two children, Howard County, Maryland, became the first US jurisdiction to mandate use of bicycle helmets for children. Schoolchildren were lectured by police about the law before its enactment. Prelaw and postlaw helmet use was observed in Howard County and two control counties: Montgomery (which sponsored a community education program) and Baltimore County (no helmet activities). Prelaw crude helmet use rates for children were 4% (95% confidence interval [CI] 0% to 10%) for Howard, 8% (95% CI 3% to 13%) for Montgomery, and 19% (95% CI 5% to 33%) for Baltimore. Postlaw rates were 47% (95% CI 32% to 62%), 19% (95% CI 11% to 27%), and 4% (95% CI 0 to 11%), respectively. The rate of bicycle helmet use by Howard County children is now the highest documented for US children. A similar increase in helmet use among children younger than 16 years nationwide could prevent about 100 deaths and 56,000 emergency-department-treated head injuries annually. Physicians and other health professionals should consider proposing and supporting the Howard County approach in their communities. PMID- 1594380 TI - Extracorporeal piezoelectric lithotripsy in unanesthetized children. AB - Extracorporeal piezoelectric lithotripsy is an effective method for treating renal pelvic stones in children. Treatment with the Wolf lithotriptor is essentially painless and can be performed without anesthesia on an outpatient basis. Real-time ultrasound is used to localize stones. In a 1-year period at the University of Utah, extracorporeal piezoelectric lithotripsy was administered to eight children with nine renal units. Of the eight children, aged 5 to 17 1/2 years, only two required sedation and only one received retreatment. No stents were placed. At 1 month posttreatment, all children were stone-free, and no significant complications occurred. PMID- 1594381 TI - Children in foster care in California: an examination of Medicaid reimbursed health services utilization. AB - The number of children in foster care in California doubled from 27,534 in 1980 to more than 62,419 in 1988, representing approximately 1% of the child population in the state. Past studies have demonstrated that children in foster care have high rates of medical and mental health problems. An examination of all Medi-Cal-paid claims was undertaken to describe the utilization of health services by children in foster care. Although children in foster care represent 4% of Medi-Cal-eligible children younger than 18 years of age, they account for approximately 5% of children using Medi-Cal services and 6.7% of expenditures, representing a 23% greater utilization rate and 41% greater expenditure rate than all children covered by Medi-Cal. Using the entire Medi-Cal population younger than 18 years of age as comparison group, examination of inpatient and outpatient service utilization for specific condition categories showed few differences between children in foster care and the comparison group except for mental health service utilization, where children in foster care were much higher users of services. PMID- 1594382 TI - Mental health service utilization by children in foster care in California. AB - An examination of Medi-Cal-paid claims was undertaken to assess the utilization of mental health services by children in California's foster care system. Using unduplicate counts of service use and diagnoses, it was determined that children in foster care account for 41% of all users of mental health services even though they represent less than 4% of Medi-Cal-eligible children. When partitioned into specific service categories, children in foster care account for 53% of all psychologist visits, 47% of psychiatry visits, 43% of Short Doyle/Medi-Cal inpatient hospitalization in public hospitals, and 27% of inpatient psychiatric hospitals. Expenditure for services paralleled utilization frequency. When compared to the non-foster care Medi-Cal-eligible child population, children in foster care have 10 to 20 times the rate of utilization per eligible child for selected services. For children in foster care, 75% of all diagnoses for billed service were accounted for by four diagnoses: adjustment disorders (28.6%), conduct disorders (20.5%), anxiety disorders (13.8%), and emotional disorders (11.9%), with clear age-related differences in the distribution of diagnoses. PMID- 1594383 TI - Bicycle helmet law for children: a case study of activism in injury control. AB - In 1990, the first regulation requiring the use of helmets for bicyclists younger than 16 years of age was passed in Howard County, Maryland. This unexpected injury control measure resulted from the convergence of multiple factors and efforts: the bicycle-related deaths of two children from the same middle school, creative students and teachers motivated by these deaths, a responsive legislator to introduce the legislation, available surveillance and research statistics supporting the need and efficacy for helmet use, increased national awareness of the importance of helmet use to prevent bicycle-related head injuries, and organized national and local public health groups to support the legislation. This case study of activism in injury control illustrates the importance of supporting research, of well-organized public health coalitions and groups, and of creative community activists motivated by local circumstances. PMID- 1594384 TI - Management of the febrile infant. PMID- 1594385 TI - Case fatality rates associated with conditions originating in the perinatal period: United States, 1986 through 1987. PMID- 1594386 TI - Liposomal amphotericin-B (AmBisome) for treatment of disseminated fungal infections in two infants of very low birth weight. PMID- 1594388 TI - Design of ICUs. PMID- 1594387 TI - Questions collaborative dexamethasone trial. PMID- 1594389 TI - Pediatricians in court. PMID- 1594390 TI - More to be learned from Crigler-Najjar patients. PMID- 1594391 TI - Verbal memory elicited by ambient odor. AB - This study examined whether an ambient odor can act as a contextual cue for retrieval of verbal stimuli. Subjects (N = 47) learned a list of 24 words while exposed to one of two odors (either jasmine incense or Lauren perfume) and subsequently relearned the list with either the same or the alternative odor present. Superior memory for the word list was found when the odor present during the relearning session was the same one that had been present at the time of initial learning, thereby demonstrating context-dependent memory. There were no differences in initial learning between the two odor conditions. No differences in pleasantness or intensity were found between the odors. PMID- 1594392 TI - Weekends and holidays and acting-out behavior of developmentally delayed women: a reply to Dr. Mark Flynn. AB - A previous report on the effect of the day of the full moon on the acting-out behavior of 20 developmentally delayed, institutionalized women showed that on the day of the full moon there were significantly more misbehaviors than on any other day during the lunar period. The records were re-evaluated to assess the frequency of acting-out behaviors on weekends and holidays as contrasted with the balance of the month. This re-evaluation indicated there was no significant difference between the weekends and holidays and the balance of the month (t = 1.14). The results were taken as support of the previous findings that on the day of the full moon there were significantly more misbehaviors than on any other day of the lunar period. PMID- 1594393 TI - Percent of agreement among raters and rater reliability of the copying subtest of the Stanford-Binet Intelligence Scale: Fourth Edition. AB - The purpose of this study was to investigate the interrater reliability of the visual-motor portion of the Copying subtest of the Stanford-Binet Intelligence Scale: Fourth Edition. Eight raters independently scored 11 protocols completed by children aged 5 through 10 years, using the scoring criteria and guidelines in the manual. The raters marked each of 10 items pass or fail and computed a total raw score for each protocol. Interrater reliability coefficients were obtained for each child's protocol, and the Kappa coefficient was computed for each item. Significant raters' reliability coefficients ranged from .82 to .91, which were low in comparison to test-retest reliability and Kuder-Richardson-20 coefficients for this and other subtests of the Stanford-Binet in the technical manual. Percent agreement among 8 raters also indicated weak reliability. Although the obtained results suggested some interrater reliability coefficients within acceptable levels, questions were raised about the scoring criteria for individual items. Caution is warranted in the use of cognitive measures which include subjective judgement of the examiner in applying scoring criteria. PMID- 1594394 TI - Relationship between cognitive style and emotional behavior. AB - In this research we examined the relationships among cognitive styles using the categorization of Bion and styles of modulation of emotional behavior (hostile content) explored with the Gottschalk, et al. method applied to the speech of 20 female and 10 male undergraduate students whose ages ranged from 20 to 35 years. Their verbalization was produced in a standard stimulus situation of 3 minutes duration. Analysis indicated a relationship between hostile attitude and cognitive styles. In particular, those who were relatively less hostile presented higher frequencies of processes classified by Bion as D2, which are characterized by an attitude of expectancy and waiting, with a tendency to defend internal psychological themas. PMID- 1594395 TI - Temporomandibular Joint dysfunction and Type A-B behavior in college students. PMID- 1594396 TI - Visual dominance in a lateral plane motor learning task. AB - Visual dominance was investigated in a motor learning task with the criterion movement being in the lateral plane of the body. The criterion movement was a 10 in. abduction of the arm. All subjects received four presentation trials for the criterion movement in each of the following conditions: dominant rotated arm, dominant unrotated arm, nondominant rotated arm, and nondominant unrotated arm. Three independent groups of 10 college-age subjects differed according to sensory stimuli given during presentation trials. The Kinesthetic group was blindfolded for presentation trials. The Visual and Kinesthetic group was unblindfolded for presentation trials. The Alternating group was blindfolded on half of the presentation trials and unblindfolded on the other half. All subjects carried out five blindfolded reproduction trials for each of the four conditions. Absolute error for the length of the reproduced movements was measured and no significant difference between groups was found. This suggests that visual dominance is reduced in movements outside the frontal plane when focal vision is not used. Planned comparison testing indicated the Alternating group was significantly more accurate than the Visual and Kinesthetic group. PMID- 1594397 TI - Characteristics of the rival and the experience of jealousy. AB - To estimate the relationship between characteristics of the third party and jealousy, 185 subjects read different jealousy-evoking scenarios and then indicated how jealous they would feel. Analysis indicated that two of the manipulated characteristics, prestige and attractiveness, significantly affected the experience of jealousy. PMID- 1594398 TI - Phenylthiocarbamide (PTC) tasting in paranoid and nonparanoid schizophrenic patients. AB - The present study reports on the association between Phenylthiocarbamide tasting for paranoid and nonparanoid schizophrenic patients. The incidence of PTC tasting is highly variable, and tasters and nontasters are frequently associated with some pathological states. 25 paranoid and 25 nonparanoid schizophrenic patients were examined for their PTC taste sensitivity. Frequency of paranoid tasters resembles the distribution of the normal population, whereas the nonparanoid patients are significantly different in their taste thresholds, with a higher incidence of nontasters. The members of this latter group have twice the incidence of psychiatric illness in their family histories as those of the former group. The significance of these findings is discussed as related to vulnerability for schizophrenia. PMID- 1594399 TI - Relationships among age, sex, and depth of sport experience with initial open task performance by 4- to 9-year-old children. AB - The purpose of this study was to assess the relative interrelationships of age, sex, and depth of sport experience on initial practice of a soccer task for 46 4- to 9-yr.-old children. Each child practiced 1 transfer trial and 3 blocks of 3 trials. Measures recorded were performance time, goal attainment, and movement accuracy. Multivariate analyses of variance and multiple regressions yielded evidence for (a) a speed-accuracy tradeoff, (b) a relation of age to goal attainment, movement accuracy, and performance time on the transfer trial, and (c) a relation of age with Block 1 performance time. Experience was more related than sex to all variables except movement accuracy in Block 1 and consistency of goal attainment. Conclusions are that age and experience are the most important to the quality of performance, and no constructs were related to consistency on this task for this age group. PMID- 1594400 TI - Age differences in performance at concentration: a pilot study. AB - 24 subjects ranging in age from 5 to 65 years individually played Concentration in pictorial and verbal formats. Consistent with age-related declines in both general and visual processing, performance was poorest for the elderly subjects on both tasks; however, there was no evidence of children's precocity. PMID- 1594401 TI - Adolescents' time perspective. AB - 201 boys and girls in Grade 11 were administered the Time Perspective Questionnaire, which assesses the type of events students typically generate when asked to think of the past and future and their temporal extension. Analysis confirms little difference between adolescent boys' and girls' time perspectives, thereby suggesting considerable convergence has occurred in boys' and girls' temporal expectations. PMID- 1594402 TI - Potentiating ballistic limb movements through voluntary production of the stretch shorten cycle. AB - The purpose of this study was to examine the effect of learning to produce voluntarily a basic biomechanical mechanism, the stretch-shorten cycle (SSC), on the acceleration of a ballistic arm movement. The task required an elbow flexion at maximal effort performed with the forearm resting upon a horizontal manipulandum. Subjects in three groups received either no augmented feedback, feedback concerning the velocity of the flexion, or a combination of feedback on velocity and feedback related to the rate of stretch of the SSC during 80 training trials. The training trials were preceded by a pretest and followed by a posttest without feedback. Analyses showed that the subjects receiving feedback concerning the SSC exhibited earlier and greater peak angular acceleration than the other groups. These findings provide evidence that acquiring the control of relevant, basic mechanisms like the SSC may be useful in facilitating tasks requiring limb movements of maximal effort. PMID- 1594403 TI - Effects of auditory imagery on the detection of a pure tone in white noise: experimental evidence of the auditory Perky effect. AB - The purpose of this study was to examine whether the auditory image of a pure tone facilitates or interferes with the auditory perception of the pure tone. The masked threshold of a pure tone in white noise with and without the image of a pure tone was compared. It was shown that, in contrast to Farah and Smith's (1983) finding of facilitation, imagery interfered with the detection of the pure tone only when the frequency of the imagined tone and the detected tone was the same. This interference was interpreted as showing the assimilation of the signal tone into imagery, i.e., the effect described by Perky in 1910, occurred in the auditory modality. An explanation of the differences between findings of interference and facilitation is offered. PMID- 1594404 TI - Geophysical variables and behavior: LXIX. Solar activity and admission of psychiatric patients. AB - Numbers of first admissions per month for a single psychiatric unit, from 1977 to 1987, were examined for 1829 psychiatric inpatients to assess whether this measure was correlated with 10 parameters of geophysical activity. Four statistically significant values were 0.197 with level of solar radioflux at 2800 MHZ in the corresponding month, -0.274 with sudden magnetic disturbances of the ionosphere, -0.216 with the index of geomagnetic activity, and -0.262 with the number of hours of positive ionization of the ionosphere in the corresponding month. Percentages of variance accounted for were very small. PMID- 1594405 TI - Percept-genetic signs of repression in histrionic personality disorder. AB - Several types of perceptual distortions of two anxiety-arousing visual stimuli are coded as repression in the Defense Mechanism Test, a tachistoscopic, percept genetic technique. Given the well-established correspondence between hysteria and repression, the study included a clinical validation of these variants of repression against the diagnosis of histrionic personality disorder. 41 subjects with evidence of this disorder on the Millon Clinical Multiaxial Inventory-II were compared with 41 nonhistrionic controls. Significantly more histrionics were coded for the type of repression in which the threatening figure is transformed into a harmless object (code 1:42), while animal- and statue-repressions, when combined (codes 1:1 and 1:2), were significantly more characteristic of the nonhistrionic group. As an unpredicted finding, significantly more histrionic subjects employed defensive strategies, currently coded as reaction formations (code 4:). Histrionic subjects without concomitant compulsive features were coded more frequently for introaggression (code 6:) compared both with nonhistrionic controls and with histrionic-compulsive subjects. The findings are discussed within the context of the available percept-genetic literature. It is suggested that the Defense Mechanism Test may be further employed to objectify and investigate the defense mechanisms of the DSM-III-R disorders. PMID- 1594406 TI - Self-concept among African-American at-risk adolescents. PMID- 1594407 TI - Intensity and direction as dimensions of competitive state anxiety and relationships with competitiveness. AB - This study examined differences in intensity and direction of symptoms of competitive state anxiety in high and low competitive subjects from the sports of rugby union, basketball, soccer, and field hockey. The 69 men were dichotomized via a median-split into high and low competitive groups based on their scores on the Sport Orientation Questionnaire. All subjects completed a modified version of the Competitive State Anxiety Inventory-2 30 minutes prior to competition. This inventory included the original intensity scale plus a direction scale on which subjects rated the extent the experienced intensity of each symptom was either facilitative or debilitative to subsequent performance. There were no significant group differences on intensity of cognitive anxiety or of somatic anxiety or on direction of somatic anxiety; however, the highly competitive group of 34 subjects reported their anxiety as more facilitative and less debilitative than the low competitive group (n = 35). This supports the proposal that sports performers' directional perceptions of their anxiety symptoms may provide further understanding of the competitive state-anxiety response. PMID- 1594408 TI - Geophysical variables and behavior: LXVIII. Distal and lunar variables and traffic accidents in Saskatchewan 1984-1989. AB - The daily total number of traffic accidents and traffic accident severity for the years 1984 to 1989 in Saskatchewan were analyzed to estimate relationships with day of the week, season of the year, and various lunar variables (lunar phase, distance of the moon from the earth, and moon-sun tidal index). A regression model with both a linear term and a trigonometric term was fitted to the data. No relationship between lunar cycles and total accidents or severity of accident was found. A larger number of total accidents was found during the winter months and weekends; however, more severe accidents tended to occur during the summer months. A slight linear trend was uncovered for total accidents over the time period under consideration. PMID- 1594409 TI - The cardiac-locomotor coupling phenomenon: the contribution of Coleman. AB - Cardiac-locomotor coupling (entrainment of heart and exercise rates) has been the subject of a number of recent studies. This paper reviews the early work of W. M. Coleman who, in 1921, published the results of his observations on humans and a variety of other species. The animal studies were carried out at the London Zoological Gardens. Coleman's findings remain relevant to those studying entrainment phenomena. They also illustrate the importance and utility of careful observation. PMID- 1594410 TI - Efficacy of awareness of strategy and overt verbalization for recall by kindergarten students. AB - Two prevailing models for teaching memory strategies for remembering were compared for two kindergarten classes (45 boys, 30 girls). A third class provided a control. One class received instruction in specific and efficacious strategies for recall on three discrete tasks: sequential memory, paired-associate memory, and clustering recall. The second class received the same instruction embedded in an overt verbalization procedure adapted form Bash and Camp (1985). The control class received as much practice as the two instructional groups but no instruction on strategy or overt verbalization. Significant gains in memory were made on paired associates at posttest for both the strategy-only group and the overt-verbalization group. Overt verbalization inhibits recall on paired associates at delayed posttest and its effect on sequential memory at posttest remains equivocal. PMID- 1594411 TI - Information loss: the primary psychological trauma of the loss of vision. AB - A psychology of blindness is proposed that contends that information loss is the most critical trauma of the loss of vision. The magnitude of information loss is emphasized with respect to vision as the primary sensory modality for obtaining information. Further, the vital role of access to information in human development and the tendency to seek information to cope with stressful circumstances are addressed. Implications for rehabilitation of blind persons are discussed. PMID- 1594412 TI - Reported head injury and sex differences in color naming, color matching, and digit-string matching. AB - It was hypothesized that the observed sex differences on three speeded tasks could be accounted for in terms of the greater incidence of head injury in men than in women. In two studies of 64 male and 66 female college students significant sex differences were found on digit-string matching and color matching tasks. When the data from those 39 subjects with reported histories of head injury were eliminated from the analysis or head-injury reports were statistically controlled, significant sex differences remained. Digit-string matching times were significantly correlated with reported head injury in both studies, suggesting that this test is sensitive to residual effects of head injury. PMID- 1594413 TI - Auditory subliminal stimulation: a re-examination. AB - Unconscious or subliminal perception has historically been a thorny issue in psychology. It has been the subject of debate and experimentation since the turn of the century. While psychologists now agree that the phenomenon of visual subliminal stimulation is real, disagreement continues over the effects of such stimulation as well as to its existence in other sensory modalities, notably the auditory. The present paper provides an overview of unresolved issues in auditory subliminal stimulation which explains much of the difficulty that has been encountered in experimental work in this area. A context is proposed for considering the effects of auditory subliminal stimulation and an overview of current investigations in this field is provided. PMID- 1594414 TI - Personal importance, motivation, and performance of older adults. AB - This investigation was conducted to examine whether older adults would improve their performance when given statements intended to make them feel important to a research study as well as statements concerning their over-all well-being. Women (n = 14) and men (n = 15) with mean ages of 76.0 yr. and 75.1 yr., respectively, were randomly assigned into a control group, a positive reinforcement group, and a group given statements of personal importance. Dependent measures on a rotary pursuit task, screw-and-nut assembly task, and an interest questionnaire were obtained during three separate visits. Data were analyzed with a 3 x 3 (Groups x Days) analysis of variance. While no significant group effects were found on any measure, a significant main effect was obtained for days, indicative of learning. PMID- 1594415 TI - Aerobic exercise in the psychological treatment of adolescents. AB - A small group of psychiatrically institutionalized adolescents (16 boys, 11 girls) were assigned to a three-day-per-week running/aerobic exercise program or a regular physical activity class. The complete program continued over 9 weeks, with 11 subjects remaining throughout the program. Dependent measures of body mass index, timed performance on a one-mile run, resting, exercise, and recovery heart rates, and measures of depression, mood-states, and self-efficacy were assessed pre-, mid-, and post-9-wk. treatment and at a 4-wk. follow-up. Improvements in depression, anxiety, hostility, confused thinking, and fatigue were shown in treated girls, with increases in vigor and self-efficacy for all treated subjects. PMID- 1594416 TI - Brain-Age quotient: age and education correlates. AB - The Brain-Age Quotient (BAQ) of Reitan has been proposed as a means of studying age-related cognitive differences. This study examined age and education correlates of the BAQ and a BAQ short form. A heterogeneous group of 100 subjects were selected from the neuropsychological testing case records published by Golden, Osmon, Moses, and Berg in 1981, Boll (undated), and Reitan (undated). Results suggest the BAQ and the BAQ short form are not significantly correlated with age and education. PMID- 1594417 TI - Hostility of asocial youth as measured by the TAT and Rorschach. AB - 23 boys and 13 girls, aged 13 to 17 yr., from two homes for delinquents were given the Thematic Apperception Test. Girls were also given the Rorschach. The 1960 Hafner and Kaplan TAT and Rorschach hostility indices were related to the 1977 Luukkonen indices (aggression-inward, aggression-outward, fantasy aggression, oral, anal and phallic content), to the Pruitt and Spilka empathy index, and to the Neiger reality index. The TAT hostility index for boys was significantly higher than that for girls; boys expressed more physical and girls more verbal hostility in TAT stories. On the Rorschach, aggression outward and inward correlated significantly with Rorschach hostility, phallic and oral themes. PMID- 1594418 TI - A novel contact-lens system to assess visual hemispheric asymmetries. AB - A soft contact-lens system for achieving unilateral visual stimulation in a free vision format is described. Initial testing with light transmittance and visual perimetry indicated that the lenses created artificial visual-field deficits. The efficacy of the lenses as a technique for lateralizing visual input was evaluated by examining within-subject differences in performance on two visuospatial tasks. Speed and accuracy of performance were greater with visual input directed to the right hemisphere. These data support the lens design as a useful alternative to tachistoscopic procedures and previous lens systems. PMID- 1594419 TI - Influence of selected reinforcers on the cardiorespiratory exercise behavior of profoundly mentally retarded youth. AB - 6 profoundly mentally retarded youth were provided a 5-wk. stair-climbing program to improve cardiorespiratory fitness behavior. Three subjects were provided verbal plus food reinforcement and the other three received verbal reinforcement during the intervention phase. Based on the visual inspection of the data, both types of reinforcement increased the number of steps taken and exercise time. PMID- 1594420 TI - Age differences in perception of risk. AB - Age differences in perception of risk and the likelihood of disregarding warning signs were examined. A total of 358 adults, between 18 and 85 years old, were asked to rate 12 warning labels with respect to (a) how risky it would be to ignore the warning, (b) how likely it was that they would disregard the warning, and (c) how familiar they were with the labels. The older groups indicated higher risk in ignoring the signs than did the younger group. The older subjects were also less willing to disregard the signs than the younger subjects. PMID- 1594421 TI - Perceptual and academic patterns of learning-disabled/gifted students. AB - This research explored ways gifted children with learning disabilities perceive and recall auditory and visual input and apply this information to reading, mathematics, and spelling. 24 learning-disabled/gifted children and a matched control group of normally achieving gifted students were tested for oral reading, word recognition and analysis, listening comprehension, and spelling. In mathematics, they were tested for numeration, mental and written computation, word problems, and numerical reasoning. To explore perception and memory skills, students were administered formal tests of visual and auditory memory as well as auditory discrimination of sounds. Their responses to reading and to mathematical computations were further considered for evidence of problems in visual discrimination, visual sequencing, and visual spatial areas. Analyses indicated that these learning-disabled/gifted students were significantly weaker than controls in their decoding skills, in spelling, and in most areas of mathematics. They were also significantly weaker in auditory discrimination and memory, and in visual discrimination, sequencing, and spatial abilities. Conclusions are that these underlying perceptual and memory deficits may be related to students' academic problems. PMID- 1594422 TI - Tactile extinction on complex stimulation in normal children. AB - The Schwartz Quality Extinction Test was administered to 221 normal right-handed children aged 4 to 7 years to find out at what age their ability to perceive complex bimanual simultaneous stimuli stabilizes. Tactile extinction was present in some 4- and 5-yr.-old children and tended to disappear later. We found a significant difference in responses between 5- and 6-yr.-old children but no difference regarding side and sex at different ages. Among the principal theories regarding the pathogenesis of extinction, incomplete maturation of attentional mechanisms seems the one which better explains extinction in younger children. PMID- 1594423 TI - Hearing threshold shift during auditory magnitude estimation. AB - The purpose of the present experiment was to determine the extent of hearing threshold shift that may occur during an auditory magnitude-estimation task involving stimulus intensities as great as 80 dB sensation level. Also, possible influences of hearing threshold shift on numerical magnitude-estimation responses and magnitude-function slopes were investigated. Results indicated that hearing threshold shift was insignificant (1-2 dB). Consistent small increases in numerical magnitude responses were observed on a magnitude-estimation task where hearing thresholds were retested between stimulus presentations versus a magnitude-estimation task where hearing thresholds were not retested. The stability of auditory magnitude functions across different conditions in the current investigation was in agreement with vibrotactile magnitude-scaling behavior observed by Fucci, et al. in 1989 and 1991. The over-all results supported the concept of an absolute, internal sensory-scaling mechanism being operable during magnitude estimation of auditory stimuli as discussed by Zwislocki and Goodman in 1980. PMID- 1594424 TI - Abortion attitudes, 1984-1987-1988: effects of item order and dimensionality. AB - The comparability of surveys is often hampered by differences in the item order of presentation. The major focus of the present study was to investigate whether a general item or a specific item at the beginning of the questionnaire would affect the endorsement as well as the scalability of a set of attitude items. By using a quasi-A-B-A experimental design for the six abortion items that appeared in the Edmonton Area Survey for the years 1984, 1987, and 1988, we found that the order of presentation of the items affected dramatically the endorsement of the abortion items. Approval of a general item was considerably higher when asked first than when asked after a specific item. In contrast, it was shown by means of a nonparametric item response theory model (the Mokken scale analysis) that the unidimensionality of the six abortion items was not affected by the manipulations of item order (i.e., the six abortion items measured the same concept in the three surveys). It was concluded that the six items are unidimensional and, therefore, create a single scale to measure the change in abortion attitudes across the three periods. PMID- 1594425 TI - Rectangles may appear to reverse like trapezia when they rotate at an uneven rate. AB - A 1983-1985 theory by Mitchell and Power predicts that, when rotating rectangles undergo certain kinds of speed fluctuation, they should appear to reverse just as trapezia do. The prediction is partially confirmed. One of two 'mimic' rectangles underwent apparent reversals more often than a control rectangle undergoing even rotation and in the same places as rotating trapezia. However, its reversal frequency was less than those of the trapezia, and a second 'mimic' slowed an inappropriate distribution of reversals round the cycle. These anomalies call for some modification to Mitchell and Power's theory, but minor qualifications may be sufficient. PMID- 1594426 TI - Happiness, time consciousness, and subjective life expectancy. AB - 84 men and 141 women enrolled at a university reported their sexes and ages, rated their happiness and their time consciousness, and estimated how many more years they expected to live. Men significantly overestimated their subjective life span compared to actuarial data. Women (but not men) who were happier tended to be younger, had greater subjective life expectancies, and felt that they had lived a smaller percentage of their total lives. Both older men and older women tended to be more time conscious. PMID- 1594427 TI - An examination of spontaneous pointing in 20- to 50-month-old children. AB - Occurrences of spontaneous pointing in 20-, 30-, 40-, and 50-mo.-old children were observed during the children's indoor or outdoor free-play periods. Observers recorded the sex of the pointer, the behavioral pattern observed, the reason for the point, the response of the adult, and the distance of the child from the adult at the time of a point. Analysis indicated a significant dip in the rate of pointing among the 30-mo.-olds while the 20- and 50-mo.-olds were observed to point most often. With the exception of the 30-mo.-olds, pointing was significantly more likely to be observed in boys. For all age groups, the point was used primarily to name. After 20 months adults were significantly less likely to respond to the point, and when they did respond they were more likely to name or demonstrate irrespective of the apparent reason for the child's point. Finally, the probability of adults' response appeared to be unrelated to the distance from the child to the adult, and further, the likelihood of an adult's response appeared to exert little influence on the rate of pointing. The results suggest that pointing may be an expressive act that can be used as a communicative gesture, but there was little evidence that any of these age groups were using the point as a ritualized gesture, that is, as an action conventionalized within the context of social interaction. PMID- 1594428 TI - Arousability and stress-related physical symptoms: a validation study of Coren's arousal predisposition scale. AB - Coren's Arousal Predisposition Scale was validated against 249 college students' self-ratings of stress-related physical symptoms and an item that assessed general level of health. As we predicted, the 126 high-arousability subjects were substantially higher in mean stress-related symptoms score and lower in general health than the 123 peers low in arousability. These data suggest that the Arousal Predisposition Scale may be a useful instrument in the study of human stress. PMID- 1594429 TI - Differentiation of fear, anger, and joy. AB - The purpose of the present study was to identify the physiological characteristics corresponding to three affects (fear, anger, and joy), which were elicited through real situations in a laboratory. The subjects were asked to rate their psychological responses using the Affect Rating Scales for each affective situation. Physiological indices (diastolic and systolic blood pressures, heart rate, respiration rate and frequency of galvanic skin response) were measured. The subjects' affects can be characterized by two functions obtained through discriminant analysis. One discriminant function separated positive from negative affects; the other set apart anger from the remaining affects. PMID- 1594430 TI - Effects of influenza and the common cold on the Stroop color-word test. AB - Two experiments examined the effects of experimentally induced upper respiratory viral infections on selective attention. In Exp. 1, 61 adults were challenged with a cold-producing virus; analysis showed no effect of infection or illness on performance of the Stroop task. In contrast to this the results of Exp. 2, involving 27 adults, showed that influenza increased distractibility from irrelevant stimuli. PMID- 1594431 TI - Extracting thresholds from noisy psychophysical data. AB - Psychophysical studies with infants or with patients often are unable to use pilot data, training, or large numbers of trials. To evaluate threshold estimates under these conditions, computer simulations of experiments with small numbers of trials were performed by using psychometric functions based on a model of two types of noise: stimulus-related noise (affecting slope) and extraneous noise (affecting upper asymptote). Threshold estimates were biased and imprecise when extraneous noise was high, as were the estimates of extraneous noise. Strategies were developed for rejecting data sets as too noisy for unbiased and precise threshold estimation; these strategies were most successful when extraneous noise was low for most of the data sets. An analysis of 1,026 data sets from visual function tests of infants and toddlers showed that extraneous noise is often considerable, that experimental paradigms can be developed that minimize extraneous noise, and that data analysis that does not consider the effects of extraneous noise may underestimate test-retest reliability and overestimate interocular differences. PMID- 1594432 TI - Attentive fields are related to focal and contextual features: a study of Muller Lyer distortions. AB - The mathematical model associated with integrative field theory was used to infer the size of attentive fields in a task involving judgments of size. A compounded Muller-Lyer task was employed in which fins between or outside the standard shafts were systematically removed. Performance on this task was simulated by a computer that generated families of theoretical functions varying in the parameter of attentive field size. Individual theoretical functions were then correlated with an empirical function obtained from real observers. The value of attentive field size that provided the best fit between functions was then selected. The results showed that, in almost all cases, the optimum size of the attentive field was smaller for the shrinkage form than for the expansion form of the Muller-Lyer pattern, that the attentive field changed more dramatically with changes in stimulus variables in the expansion form than in the shrinkage form, and that changes in viewing distance had little effect on the optimum size of the attentive field. It was concluded that the attention was involved both in figure ground segregation and in maintaining object constancy. The similarity of these results to data obtained in recognition and detection tasks was noted. PMID- 1594433 TI - What makes targets redundant? AB - Two letter-classification experiments that investigated target-redundancy effects on reaction time (RT) were conducted. Both experiments were replicated with choice reaction time (CRT) and go/no-go (GNG) procedures. In each experiment, there were two single-target conditions, one with a noise letter and one without. In one experiment, the letter classes were two letters that could be of either case. In the second experiment, each class consisted of two different capital letters. In both experiments, there were two redundant-targets conditions, one with identical targets and one with the different members of a class. In both of the GNG experiments, redundancy gains were obtained comparing the different targets condition with the no-noise, single-target condition. Redundant stimuli are ones that lead to the same response. Visually different stimuli may be processed in parallel and jointly activate a response. GNG procedures are more sensitive than CRT in the investigation of redundancy effects. PMID- 1594434 TI - The role of central and peripheral vision in perceiving the direction of self motion. AB - Three experiments were performed to examine the role that central and peripheral vision play in the perception of the direction of translational self-motion, or heading, from optical flow. When the focus of radial outflow was in central vision, heading accuracy was slightly higher with central circular displays (10 degrees-25 degrees diameter) than with peripheral annular displays (40 degrees diameter), indicating that central vision is somewhat more sensitive to this information. Performance dropped rapidly as the eccentricity of the focus of outflow increased, indicating that the periphery does not accurately extract radial flow patterns. Together with recent research on vection and postural adjustments, these results contradict the peripheral dominance hypothesis that peripheral vision is specialized for perception of self-motion. We propose a functional sensitivity hypothesis--that self-motion is perceived on the basis of optical information rather than the retinal locus of stimulation, but that central and peripheral vision are differentially sensitive to the information characteristic of each retinal region. PMID- 1594435 TI - Consequences of allocating attention to locations and to other attributes. AB - Simple reaction time to a light target may be lengthened when the light is preceded by a noninformative stimulus at the same location. This is known as inhibition of return. Does inhibition of return result if the relation between successive stimuli is defined in terms of color or orientation? Subjects pressed a key when a small square was displayed. In Experiments 1-3, location and color of the square were manipulated; there was inhibition of return based on location, but not on color. In Experiments 4-5, a confounding of color and luminance was eliminated, with no change in results. In Experiments 6-7, the background was composed of vertical stripes and the squares were composed of left- or right oriented diagonal stripes. There was evidence of inhibition of return based on location, but not on orientation. These data support the idea that location is processed differently from other features. PMID- 1594436 TI - The role of attention in different visual-search tasks. AB - Observers viewed displays containing a variable number of distractors of one color and a target of another color. In some experiments, the target and distractors maintained their color from trial to trial; in others, they reversed unpredictably. Observers made a speeded two-choice judgment concerning either the presence, the color, or the shape of the odd-colored target. With only one exception, all of these conditions produced the same pattern of results: reaction times remained constant as the number of distractors increased. The exceptional result occurred when observers judged the shape of the odd-colored target and the color of the target and distractors reversed unpredictably. In this case, reaction times decreased as the number of distractors increased. These results are interpreted in terms of the attentional requirements of the different judgments and the mechanisms that guide attention. PMID- 1594437 TI - The word-superiority effect does not require a T-scope. AB - Six experiments examined the possibility of obtaining a word-superiority effect (WSE) without the use of brief stimulus exposures or a poststimulus mask. In each experiment, subjects were presented a stimulus string and two alternative strings that differed by a single letter (Reicher, 1969). The alternatives and stimulus remained in view until subjects responded, and subjects were under no pressure to respond quickly. In Experiments 1-3, the stimuli were presented in very small type so that they were difficult to see. Subjects were significantly more accurate with words than with nonwords, letters embedded among digits, or letters embedded among number signs (#s). In Experiments 4 and 5, the stimuli were embedded in a simultaneously present pattern mask. Subjects were significantly more accurate with words than with single letters by themselves. In the final experiment, the stimuli were presented in a mask with specific spatial frequency characteristics, and performance was significantly better with words than with nonwords. The WSE is a more general phenomenon than previously supposed; it is not limited to a tachistoscopic exposure. PMID- 1594438 TI - Metacognition in psychophysical judgment: an unfolding view of comparative judgments of mental workload. AB - An experiment is reported in which it was found that when subjects were required to indicate which of two visual extents was more difficult to categorize as "long" or "short," they executed these categorizations and then measured the distance of the representation of each stimulus from the long-short category boundary; the stimulus nearer the boundary was judged to be the more difficult. When they were requested to indicate which was easier to categorize, they selected the alternative that was farther. Coombs's theory of data (1952, 1964) and his unfolding theory of preferential choice (1950, 1964) provided the conceptualization of metacognition in this psychophysical task context. Strong support for the probabilistic version of unfolding theory was obtained from the observed selective effects of laterality on the levels of stochastic transitivity attained for various classes of triples and the reliably longer times for comparisons with bilateral pairs than with unilateral pairs. The semantic congruity effects obtained, together with the changes in the form of the relationship between probability and response time as a function of practice, can be best accounted for by an evidence accrual theory in which the distances from the active reference point are measured and compared with a criterion on each evidence accrual. No support is provided for the view that propositionally based semantic "ease"-"difficulty" codes serve as the basis for these metacognitive comparative judgments of ease and difficulty. PMID- 1594439 TI - Laterality and modality-specific effects of chronic pain. AB - Previous investigations indicated that thresholds to nonpainful tactile stimuli were elevated in chronic-pain patients when compared with pain-free individuals (Seltzer & Seltzer, 1986; Seltzer et al., 1988). The present study attempted to determine whether thresholds to tactual and visual stimuli also were elevated by chronic pain. Furthermore, lateralization of the pain effect on tactile thresholds was assessed by obtaining thresholds from both left and right arms. A decrease in tactile sensitivity to nonpainful stimuli in chronic-pain patients was confirmed, but laterality of the effect was not demonstrated. Visual thresholds were not significantly affected by chronic pain. The data in the present study, taken together with other data, support the proposition that pain does not affect right hemispheric processes more than left hemispheric processes. PMID- 1594440 TI - Time-shrinking: a discontinuity in the perception of auditory temporal patterns. AB - Recent research at our laboratories in the field of human auditory time perception revealed that the duration of short empty time intervals (less than approximately 200 msec) is considerably underestimated if they are immediately preceded by shorter time intervals. Within a certain range, the amount of subjective time shrinking is a monotonous function of the preceding time interval; the shorter it is, the more it shrinks its successor. In the present study, the preceding interval was kept constant at 50 msec, and the following interval, for which the duration had to be judged, varied from 40 to 280 msec. The results showed that at up to 100 msec, the perceived duration increased to a much lesser extent than did the objective duration. Beyond 120 msec, the perceived duration quickly increased and reached a veridical value at 160 msec. Such a sudden change of perceived duration in a temporal pattern in which the objective duration varies gradually indicates a typical example of categorical perception. We suggest that such a categorization of the time dimension might be a clue for processes of speech and music perception. PMID- 1594441 TI - Kluyveromyces contains a functional ABF1-homologue. AB - ABF1 is a multifunctional protein present in Saccharomyces cerevisiae, involved in transcription-activation and -repression as well as in DNA-replication. Several lines of evidence indicate the occurrence in the related species Kluyveromyces lactis of a protein having similar properties to those of ABF1 in S. cerevisiae. In order to identify conserved functional domains in ABF1, we have cloned and sequenced the gene encoding the ABF1-homologue from K. lactis. KIABF1 is much smaller than ScABF1 (54.6 vs. 81.7 kD). It exhibits extensive homology with its S. cerevisiae counterpart in the N-terminal region. The C-terminal domain however, is divergent, with the striking exception of a stretch of 20 amino acids, which is virtually identical in the two proteins. KIABF1 can substitute ABF1 in S. cerevisiae, emphasizing the conservation of the multiple functions of this protein. PMID- 1594442 TI - Effect of the higher-order structure of tRNAs on the stability of hybrids with oligodeoxyribonucleotides: separation of tRNA by an efficient solution hybridization. AB - In the course of developing a method to purify a single tRNA species efficiently, we have examined hybridization efficiencies between some tRNAs and short oligodeoxyribonucleotide probes both by the filter and solution hybridization methods without denaturants. The hybridization efficiencies varied considerably among probes which are complementary to different regions of the tRNAs, although there was little efficiency variation in the probes toward DNA substrates including the same nucleotide sequence. This efficiency variation was shown to be due to tRNA-specific higher-order structures as well as a hypermodified nucleotide in the anticodon loop. Characterization of the tRNA-probe hybrids by both nondenaturing gel electrophoresis and chemical modification showed the existence of two stable hybridizing states as a function of ionic strength. Our results indicate that RNA molecules with a number of intramolecular base pairings are able to form stable hybrids with complementary sequences under nondenaturing conditions. On the basis of these data, an appropriate probe was designed to successfully purify yeast tRNA(Phe) by making a tRNA(Phe)-probe hybrid, which has a longer retention time in hydroxyapatite high performance liquid chromatography than the tRNA(Phe) itself. PMID- 1594443 TI - Mapping the transactivation domain of the Oct-6 POU transcription factor. AB - The POU transcription factor Oct-6 is expressed in embryonic stem cells, glial progenitor cells and in a restricted set of neurons in the CNS. The protein has been shown to act as a transactivator as well as a repressor. Here we show that the Oct-6 protein activates transcription from three different promoters in HeLa cells. The ability to activate a minimal tk promoter via a multimerized IgH enhancer octamer motif relies on a domain within the aminoterminal third of the protein. Parts of this domain can be deleted without abolishing transactivation, suggesting that there is functional redundancy within this region. The transactivation domain of the Oct-6 protein is different from other described activation domains in that it is highly glycine and alanine rich. PMID- 1594444 TI - Tissue-specific expression in the salivary glands of transgenic mice. AB - Using a DNA construct, named Lama, derived from the murine parotid secretory protein (PSP) gene, we have obtained salivary gland specific gene expression in transgenic mice. Lama is a PSP minigene and allows analysis of the PSP gene 5' regulatory region by transgenesis. We show here that the regulatory region included in Lama with 4.6 kb of 5' flanking sequence is sufficient to direct expression specifically to the salivary glands. The expression level in the parotid gland is only about one percent of the PSP mRNA level, while that of the sublingual gland is near the PSP mRNA level. This suggests significant differences in the PSP gene regulation in the two glands. In addition, Lama is a secretory expression vector in which cDNAs or genomic fragments can be inserted. We demonstrate that the Lama construct can direct the expression of a heterologous cDNA encoding the C-terminal peptide of human factor VIII to salivary glands and that the corresponding peptide is secreted into saliva. PMID- 1594445 TI - Determination of the DNA sequence recognized by the bHLH-zip domain of the N-Myc protein. AB - The DNA-binding domain of the murine N-Myc protein, comprising the basic helix loop-helix-zipper (bHLH-zip) region was expressed as a fusion protein in E. coli. The affinity purified glutathione-S-transferase-N-Myc fusion protein (GST-N-MYC) was used to select the N-Myc specific DNA-recognition motif from a pool of random sequence oligonucleotides. After seven rounds of binding-site selection, specifically enriched oligonucleotides were cloned and sequenced. Of 31 individual oligonucleotides whose sequences were determined, 30 contained a common DNA-motif, defining the hexameric consensus sequence CACGTG. We confirm by mutational analysis that binding of the N-Myc derived bHLH-zip domain to this motif is sequence-specific. PMID- 1594446 TI - Reduction of a conserved Cys is essential for Myb DNA-binding. AB - The human c-Myb gene product is a regulator of transcription with intrinsic DNA binding activity located in two of three aminoterminal repeats R2R3. Three purified recombinant c-Myb proteins, a 42 kD protein corresponding to the amino terminal half (HM42), and two proteins representing R2R3 or R1R2R3 (HMR23 and HMR123) have been analyzed either as purified proteins or present in bacterial extracts in gelshift analyses using a high-affinity DNA oligonucleotide. The purified proteins are inactive in DNA-binding unless supplemented with a reducing agent such as dithiothreitol (DTT) in vitro. Alternatively a cellular nuclear extract (Nex) from HeLa cells strongly activates the binding. This effect is dose dependent and sensitive to heat. The Nex does not lead to changes in the Myb-DNA mobility shift assay excluding a direct association of the complex with a cellular component. Site-directed mutagenesis of the aminoacid residue 130, a single conserved cysteine in HMR23 to serine almost completely abolishes DNA binding. Oxidation by diamide or alkylation by N-ethylmaleimide (NEM) of the Myb proteins in vitro inhibit their interaction with DNA whereby the diamide effect is reversible by addition of excess of DTT. Nex prepared from COS cells transfected with c-myb leads to Myb-DNA interaction which is not responsive to DTT but sensitive to NEM and diamide. Our data indicate that the reduced cysteine of Myb is essential for its DNA-binding and that Myb function may be regulated by a reduction-oxidation mechanism. PMID- 1594447 TI - Isolation and characterization of the cDNA encoding human DNA methyltransferase. AB - We have cloned a series of overlapping cDNA clones encoding a 5194 bp transcript for human DNA methyltransferase (DNA MTase). This sequence potentially codes for a protein of 1495 amino acids with a predicted molecular weight of 169 kDa. The human DNA MTase cDNA has eighty percent homology at the nucleotide level, and the predicted protein has seventy-four percent identity at the amino acid level, to the DNA MTase cDNA cloned from mouse cells. Like the murine DNA MTase, the amino terminal two-thirds of the human protein contains a cysteine-rich region suggestive of a metal-binding domain. The carboxy terminal one-third of the protein shows considerable similarity to prokaryotic (cytosine-5) methyltransferases. The arrangement of multiple motifs conserved in the prokaryotic genes is preserved in the human DNA MTase, including the relative position of a proline-cysteine dipeptide thought to be an essential catalytic site in all (cytosine-5)-methyltransferases. A single 5.2 kb transcript was detected in all human tissues tested, with the highest levels of expression observed in RNA from placenta, brain, heart and lung. DNA MTase cDNA clones were used to screen a chromosome 19 genomic cosmid library. The DNA MTase-positive cosmids which are estimated to span a genomic distance of 93 kb have been localized to 19p13.2-p13.3 by fluorescence in situ hybridization. Isolation of the cDNA for human DNA MTase will allow further study of the regulation of DNA MTase expression, and of the role of this enzyme in establishing DNA methylation patterns in both normal and neoplastic cells. PMID- 1594448 TI - SwaI, a unique restriction endonuclease from Staphylococcus warneri, which recognizes 5'-ATTTAAAT-3'. AB - A novel class-II restriction endonuclease designated SwaI was purified from Staphylococcus warneri. This enzyme cleaves adenovirus 2 DNA, SV40 DNA and M13mp7 at one site each, but does not cleave lambda, PhiX174, pBR322 or pBR328 DNA. SwaI recognizes the octanucleotide sequence 5'-ATTTAAAT-3', cleaving in the center of the recognition sequence creating blunt ended DNA fragments. SwaI was used to digest chromosomal DNA from various microorganisms and human cells. PMID- 1594449 TI - Monofunctional DNA-platinum(II) adducts block frequently DNA polymerases. AB - The question of whether monofunctional DNA platinum(II) adducts block synthesis of DNA by purified DNA polymerases of different types and origin has been investigated by comparing the time dependence of synthesis arrest and of DNA adduct formation. Activated salmon testis DNA is used as a suitable substrate for DNA synthesis allowing to probe inhibition by platinum(II) monoadducts for the variety of inherent template-primers. Reaction amplitudes are related to defined mixtures of dichloro and chloroaqua platinum(II) complexes. It is found that (i) all investigated DNA polymerases seem arrested (100% efficiency) at bifunctional DNA adducts. (ii) human DNA polymerase beta bypasses most of the monofunctional lesions of the three platinum(II) complexes investigated. (iii) Klenow fragment is blocked by monoadducts with increasing efficiency in the order cis diamminechloroaquaplatinum(II) (0%) less than meso-[1,2-bis(2,6- dichloro-4 hydroxyphenyl)ethylenediamine] chloroaquaplatinum(II) (50%) less than trans diamminechloro-aquaplatinum(II) (75%). (iv) Escherichia coli DNA polymerase I, Thermus aquaticus DNA polymerase, Physarum polycephalum DNA polymerase alpha, and calf thymus DNA polymerase alpha appear to be arrested by monoadducts. According to these examples, blocking efficiencies depend on the cis/trans-stereogeometry of fixation of the carrier ligands at platinum(II) residues, on the size/chemical nature of the platin(II) carrier ligand and on the type/origin of DNA polymerase. PMID- 1594450 TI - The human M creatine kinase gene enhancer contains multiple functional interacting domains. AB - Cis-elements (-933 to -641) upstream of the human M creatine kinase gene cap site contain an enhancer that confers developmental and tissue-specific expression to the chloramphenicol acetyltransferase gene in C2C12 myogenic cells transfected in culture. Division of the enhancer at -770 into a 5' fragment that includes the MyoD binding sites (-933 to -770) and a 3' fragment that includes the MEF-2 binding site (-770 to -641) resulted in two subfragments that showed minimal activity but in combination interacted in a position- and orientation-independent fashion to enhance activity of the SV40 promoter in transient transfection experiments. A 5' enhancer construct (-877 to -832) including only one (the low affinity) MyoD binding site was active when present in multiple copies. In contrast, a 3' enhancer construct (-749 to -732) including the MEF-2 binding site was inactive even when present in multiple copies. However, if the 5' construct was extended to include the high-affinity MyoD binding site (-877 to -803) the 5' and 3' constructs interacted in a position- and orientation-independent fashion to activate the SV40 promoter. Thus, the human M creatine kinase enhancer comprises multiple functional interacting domains. PMID- 1594451 TI - Chimeric and truncated RNAs in Trypanosoma brucei suggest transesterifications at non-consecutive sites during RNA editing. AB - RNA editing adds and removes uridines at specific sites in several mitochondrial transcripts in kinetoplastid parasites probably as specified by guide RNAs (gRNAs) that are complementary to the final edited sequence. Editing has been postulated to involve transesterification which predicts (1) chimeric molecules with a gRNA covalently attached by its non-encoded oligo U tail to an internal editing site in the mRNA and (2) the corresponding truncated 5' portions of the mRNAs. We have characterized cDNAs representing a large number of both types of intermediates from Trypanosoma brucei. The lengths of both U tails and encoded gRNA sequences vary greatly in length. The majority of encoded gRNA sequences are shorter than predicted based on their minicircle coding sequences. Analysis of the predominant sites of gRNA attachment in chimeras suggests that the transesterifications that religate the truncated 5' mRNAs may proceed more rapidly at editing sites at the 5' end of an editing domain and at sites of U deletion. Partially edited sequences in the mRNA portion of chimeras and at the 3' ends of truncated 5' mRNAs also indicate a non-consecutive order of site selection during RNA editing. PMID- 1594452 TI - v-Fps-responsiveness in the Egr-1 promoter is mediated by serum response elements. AB - Egr-1, a mitogen-responsive transcription factor, is rapidly induced by v-Fps in the absence of protein synthesis. Thus, Egr-1 is a primary response to the protein-tyrosine kinase activity of v-Fps. To determine the v-Fps-responsive elements in the Egr-1 promoter, deletion mutants of the Egr-1 promoter were used in transient expression assays. A v-Fps expression vector was contransfected into NIH 3T3 cells with chloramphenicol acetyl transferase (CAT) gene expression vectors under the control of the Egr-1 promoter or the Egr-1 promoter containing various deletions. Responsiveness to v-Fps was restricted to a region that contained repeated CC(A/T)6GG sequences, known as CArG boxes. CArG boxes form the core of serum response element (SREs). v-Fps-induced Egr-1 promoter activation was lost by sequential removal of four tandemly repeated SREs. This region, containing four SREs, was found to be sufficient for maximal Egr-1 induction by v Fps when placed upstream from a heterologous promoter. Individual SREs from this region were able to respond to v-Fps, however, the activation of the individual SREs was lower than that observed for the clustered SREs. These data suggest that v-Fps-responsiveness in the Egr-1 promoter is mediated by SREs. PMID- 1594453 TI - Identification of exon sequences and an exon binding protein involved in alternative RNA splicing of calcitonin/CGRP. AB - Transcripts derived from the 6 exon CALC I gene are differentially processed in a tissue-specific fashion to include or exclude a calcitonin-specific exon 4. All cell types which transcribe a second calcitonin/CGRP gene, CALC II, exclude exon 4. Substitution of the first 30 nucleotides of CALC I exon 4 with analogous CALC II sequence was sufficient to prevent recognition of exon 4 in in vitro or in vivo RNA splicing systems. UV crosslinking detected a approximately 66 kDa RNA binding protein in HeLa nuclear extract which interacted with CALC I proximal exon sequence, but not CALC II or mutant sequences. UV crosslinking of this protein was inhibited by addition of nuclear extract from a cell type which normally causes exclusion of exon 4. These results identify an important regulatory element within exon 4 and support a model in which calcitonin production requires protein interaction with this sequence to facilitate exon recognition. PMID- 1594454 TI - Cloning and sequencing of the murine homologue of the human splicing factor U2AF65. PMID- 1594455 TI - Cloning of the gene encoding RNase binase from Bacillus intermedius 7P. PMID- 1594456 TI - Identification of L10e/L12e ribosomal protein genes in Babesia bovis. PMID- 1594457 TI - Bsp423I, a novel isoschizomer of BbvI from Bacillus recognizing 5'-GCAGC-3'. PMID- 1594458 TI - Ssp5230I, a novel isoschizomer of AatII from Streptomyces recognizing 5'-GACGT/C 3'. PMID- 1594459 TI - Nonconserved segment of the MutL protein from Escherichia coli K-12 and Salmonella typhimurium. PMID- 1594460 TI - Rapid extraction of fungal DNA for PCR amplification. PMID- 1594462 TI - Factors related to amphotericin-B-induced rigors. PMID- 1594463 TI - Implementation of the American Pain Society Quality Assurance Standards for Relief of Acute Pain and Cancer Pain in oncology nursing practice. AB - Cancer pain represents a high-incidence problem that requires ongoing monitoring and evaluation. The recently published American Pain Society Quality Assurance Standards for Relief of Acute Pain and Cancer Pain provides an excellent basis for developing a quality assurance (QA) program in cancer pain assessment and management. These standards contain five critical areas for monitoring and evaluation related to cancer pain. The purpose of this article is to provide a useful framework for oncology nurses to develop a QA program in cancer pain assessment and management. The Oncology Nursing Society Position Paper on Cancer Pain and the American Nurses Association/Oncology Nursing Society Standards of Oncology Nursing Practice are incorporated into the framework to develop specific monitoring criteria. Practical suggestions are provided for implementing a QA program on cancer pain in a variety of oncology practice settings, using the standards of the American Pain Society. PMID- 1594461 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1594464 TI - Fatigue mechanisms in patients with cancer: effects of tumor necrosis factor and exercise on skeletal muscle. AB - Fatigue is a common adverse effect of cancer and its therapy. However, the specific mechanisms underlying cancer fatigue are unclear. One physiologic mechanism may involve changes in skeletal muscle protein stores or metabolite concentration. A reduction in skeletal muscle protein stores may result from endogenous tumor necrosis factor (TNF) or from TNF administered as antineoplastic therapy. This muscle wasting would require patients to exert an unusually high amount of effort to generate adequate contractile force during exercise performance or during extended periods of sitting or standing. This additional effort could result in the onset of fatigue. Additionally, cancer fatigue may develop or become exacerbated during exercise as a consequence of changes in the concentration of skeletal muscle metabolites. These biochemical alterations may interfere with force that is produced by the muscle contractile proteins. These physiologic changes may play a role in the decision to include exercise in the rehabilitation plans of patients with cancer. They also may affect ideas about fatigue. PMID- 1594465 TI - Perceptions of quality of life and quality of care for patients with cancer receiving biological therapy. AB - This retrospective, descriptive study was undertaken to identify patient and family perceptions about quality of life (QOL) and quality of care (QOC) after experimental biological therapy. A mail survey that included instruments designed to measure QOL (the Profile of Mood States [POMS] and the Linear Analogue Self Assessment [Lasa]) and QOC was sent to patients (response rate, 60%) and to relatives of deceased patients (response rate, 70%). Bivariate and multivariate statistics were used to analyze the data. Patients reported a relatively good quality of life, as measured by POMS and LASA scores. The majority of living patients and of family members of deceased patients were positive about the QOC received; relatives were significantly less positive than patients. Four components were significant in respondents' assessment of QOC: adequate symptom control, availability of support services, communication with the medical team, and receiving information about response to treatment. The findings suggest that there is a need to supplement survival data and biomedical outcomes with information about patient and family perceptions about care and treatment. PMID- 1594466 TI - Sources of hope in chronic illness. AB - Patients with many types of diagnosis find that hope is an important strategy in coping with their illness. One purpose of this study was to identify and explore the sources that patients with chronic illnesses report as being supportive of their hope. Another purpose was to determine if the sources differ between patients with cancer and patients with other chronic illnesses. A combination of Stotland's work on hope and Lazarus and Folkman's work on coping formed the conceptual framework for this study. Ninety patients, 45 with cancer and 45 with other chronic illnesses, were interviewed using an investigator-developed interview guide. Using chi-square and t-test analyses, no statistically significant differences were found between patients with cancer and patients with other chronic illnesses in any responses to the interview questions. The most commonly reported sources for supporting hopefulness were family, friends, and religious beliefs. Patients were able to identify specific ways in which these sources helped to support their hope. The majority of patients reported positive attitudes about their illnesses, with transient periods of lowered hope related to illness. They also described specific cognitive or behavioral strategies used for maintaining hope. The results of this study provide additional insight into the coping strategies of adults with a chronic illness. PMID- 1594467 TI - The problem of pain in children with cancer: a research review. AB - Pain in a child with cancer poses significant challenges for nurses. However, little research has been conducted in the area of pediatric cancer pain to guide clinical assessments and interventions. The purpose of this paper is to present a review of the research studies conducted on pediatric cancer pain over 13-1/2 years. The review of the cancer pain research studies is organized around several concepts that include approaches to cancer pain assessment and management as well as the presentation, incidence, and etiology of pain associated with childhood malignancy. Relevant clinical findings from the review of the literature are highlighted. Emphasis is on the major nursing implications from these studies, and suggestions are made for future nursing research. PMID- 1594468 TI - The challenge of adult respiratory distress syndrome during interleukin-2 immunotherapy. AB - During the last eight years, a substantial effort has been undertaken to develop new immunotherapeutic modalities to treat patients who have advanced cancer. One of the therapies used in this effort is the administration of interleukin-2 (IL 2) with or without lymphokine-activated killer (LAK) cells. Tumor responses have been documented in some patients undergoing this treatment, but it can cause life threatening complications. Adult respiratory distress syndrome (ARDS), a term describing an acute respiratory failure episode, is one of these complications. Unless recognized and treated early, ARDS can progress to severe respiratory failure requiring intubation. The use of IL-2 for cancer treatment still is being studied, but this agent soon may receive approval from the Food and Drug Administration and become more widely used. Knowledge about its toxicity and the need for careful patient monitoring are paramount when administering this therapy. PMID- 1594469 TI - The epidemiology of cervical cancer and its precursors. AB - Cervical cancer is considered to be a preventable disease because of its lengthy preinvasive state, the effectiveness of screening programs, and the availability of effective treatment options for preinvasive lesions. Thus, identifying women with a greater probability of developing the disease is important to promoting early detection and instituting prompt treatment. Questions concerning risk factors that influence a woman's chances of developing cervical cancer are being addressed through research. Nurses who understand the epidemiology of cervical cancer and who are skilled in taking comprehensive health histories can play a major role in early detection and prompt treatment of cervical cancer by educating all women, including sexually active teenagers, about obtaining regular gynecologic screening exams. PMID- 1594470 TI - The use of distraction and imagery with children during painful procedures. AB - The effectiveness of a pediatric pain management program was examined using a multiple case study design. This study examined both the children's pain experience during cancer treatment, as well as their parents' anxiety and behavioral stress. Fourteen children were videotaped while receiving lumbar punctures during an 8-12 month period. Baseline data were obtained at the first of three visits prior to the introduction of relaxation, imagery, and distraction exercises. Self-ratings of child fear and parent anxiety, videotaped observations of child and parent behavior, and child pain ratings were obtained at all three visits. The children's behavioral responses to the procedure varied considerably, but their fear scores were stable and their reports of pain decreased over time. Parents reported high-trait, low-state anxiety scores that were stable over time. They were observed to be very supportive during the procedures. Implications for further research in this area and recommendations for practice are presented. PMID- 1594471 TI - Pneumocystis carinii pneumonia (PCP) and your child: a parent information booklet. AB - A parent education booklet describing Pneumocystis carinii pneumonia (PCP) was prepared by the Pediatric Branch of the National Cancer Institute. In addition to information about prophylaxis and treatment of PCP, the booklet discusses overall care of children infected with human immunodeficiency virus. PMID- 1594472 TI - Outpatient oncology chemotherapy documentation tool. AB - Time-saving documentation tools are vital in today's patient care environment. One such tool was designed to facilitate charting of the wide variety of information generated during outpatient chemotherapy administration. It is anticipated that this tool eventually will be incorporated as a component of a quality assurance program. PMID- 1594473 TI - Assessing the emotional status of patients. PMID- 1594474 TI - Averting adhesive-related skin reactions in patients with port entry sites. PMID- 1594475 TI - Using hypothermic analgesia for port access. PMID- 1594476 TI - Vegetable sprays can make cleanup easier. PMID- 1594477 TI - Using the FDA's Device Experience Network. PMID- 1594478 TI - Changes in nucleolar transcriptional activity in hepatitis B virus-associated chronic liver diseases. Preliminary results from a quantitative study of silver stained nucleoli. AB - Modifications of gene expression may occur in hepatitis B virus (HBV)-related chronic liver diseases, possibly also involving ribosomal RNA (rRNA) genes contained in the nucleolus. Changes in the level of transcriptional activity of rRNA genes are reflected by variations in the number and/or size of the nucleoli. Therefore a quantitative analysis of the silver-stained nucleoli (AgNus) was performed in a small series of liver needle biopsies from patients with HBV+ chronic persistent hepatitis (CPH) (n = 3), HBV+ chronic active hepatitis (CAH) (n = 3) and HBV+ cirrhosis (CIR) (n = 3). In each case, 100 hepatocytes were selected. The number of the nucleoli (AgNuN), their total area (tAgNuA), the average area of each nucleolus (xAgNuA), the nuclear area (NA) and the percentage ratio of tAgNuA related to NA (rAgNuA) were determined for each hepatocyte nucleus. The pooled mean values of all the features were significantly different (p less than 0.001) among the case groups. The results point towards a remarkable increase of nucleolar activity in CAH in comparison with CPH, whereas an additional increment of this activity is associated with the progress from CAH to CIR. PMID- 1594479 TI - Histological and clinical features of non-familial primary parathyroid hyperplasia. AB - Relations between histopathological characteristics and clinical data were retrospectively investigated in patients with sporadic primary hyperparathyroidism due to hyperplasia. The study comprised 100 patients with chief cell hyperplasia and nine with hyperplasia of the water-clear cell type operated on during the period of 1959-1989. The chief cell hyperplasia was associated with a renal stone disorder as the predominant symptom in 41 patients, psychiatric/neuromuscular manifestations in 26 patients, while 23 patients were apparently asymptomatic. The remaining ten patients had miscellaneous symptoms. Patients with renal stones were more frequently of the male sex and generally had lower serum calcium values and less marked increments in total parathyroid glandular weights than patients with other symptoms or those who were overtly asymptomatic. Two main morphological patterns, diffuse and nodular hyperplasia, were encountered in chief cell hyperplasia. Diffuse hyperplasia was usually found in moderately enlarged glands, with a less variable size and morphology. It was also more prevalent among young patients having moderate hypercalcaemia and either recurrent renal stones or neuromuscular/psychiatric symptoms. The glands affected by nodular hyperplasia were asymmetric in size with a variable cellular arrangement and a high proportion of oxyphil cells. Nodular hyperplasia was irrespective of symptoms more frequent in the elderly patients. Water-clear cell hyperplasia was not encountered during the last decade of the study and until then it was an occasional finding in patients with marked hypercalcaemia. In this histological entity the glands were greatly and asymmetrically enlarged. PMID- 1594480 TI - Chromogranin A immunoreactivity compared with argyrophilia, calcitonin immunoreactivity, and amyloid as tumour markers in the histopathological diagnosis of medullary (C-cell) thyroid carcinoma. AB - Applying the WHO criteria for the histopathological diagnosis of medullary thyroid carcinoma (MTC)--as well as the criterion that a significant amount of argyrophil cells, amyloid deposits, or calcitonin (CT) immunoreactive cells shall be present--122 cases were identified from the files of the Swedish Cancer Registry. Both non-occult (n = 110) and "occult" (less than 1 cm in diameter) (n = 12) MTCs were included. Both primary tumours (n = 91) and metastatic lesions (n = 31) were investigated. The specimens available were all only conventionally formalin-fixed and paraffin-embedded. The presence of neoplastic cells immunoreactive with antisera against chromogranin A (Chr A) was compared with that of the other three MTC markers. Chr A immunoreactive cells were present in practically all the cases. Similar results were obtained when the argyrophil reaction alone and CT immunoreactivity alone were used as markers. When two of the three MTC markers were combined, it was found that virtually everyone of the 122 tumours could be identified as a MTC. In contrast, the presence of amyloid deposits was found to be a less constant MTC marker; whereas 94% of the primary tumours had amyloid deposits, they were present in only approximately 70% and 60% of the metastatic and "occult" tumours respectively. No differences in the staining reaction patterns were found between familial (n = 18) and the sporadic (n = 104) types of MTC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594481 TI - Nucleolar silver staining patterns of lymphocytes in sarcoidosis. AB - Bronchoalveolar lavage lymphocytes from 15 patients with pulmonary sarcoidosis and 8 healthy controls were investigated for nucleolar silver staining patterns and lymphocyte subpopulations. Patients with sarcoidosis had increased numbers of silver stained dots versus controls (2.20 +/- 0.24 versus 1.78 +/- 0.07; p less than 0.001). The number of silver stained dots showed the strongest positive correlation to helper cells (OKT 4+) (r = 0.781; p less than 0.0001). These results may be interpreted as further evidence of lymphocytic activation, especially of helper cells (OKT 4+) in pulmonary sarcoidosis. PMID- 1594482 TI - Fetal and perinatal infections. A consecutive study. AB - 118 cases of second trimester abortions, stillbirths, and perinatal deaths together with the placentas and case records were studied histologically and microbiologically to evaluate the incidence of infection and to assess possible correlations to certain clinical parameters. The infection rate was 39.4%, highest in the second trimester abortions (58.2%), where infection was also considered the most frequent cause of death (45.5%), though mostly without maternal signs of infection. 36.6% of cases with histological inflammation exhibited positive culture results. The value of ordinary culture of the placenta and fetus is questionable, at least if not performed immediately after delivery. A significant correlation between infection and vaginal bleeding during pregnancy, ruptured membranes of more than 24 hours duration, and spontaneous labour was found. No protective effect of intact membranes was found. PMID- 1594483 TI - Comparative immunohistochemical analysis between jaw myxoma and mesenchymal cells of tooth germ. AB - The histogenesis of jaw myxoma is still debated. According to some authors it arises from the primitive mesenchymal components of developing teeth. In this study, we have studied the expression of S-100 protein and vimentin in dental follicle, dental papilla and periodontal ligament cells using monoclonal and polyclonal antibodies. Myxoma of the jaw expresses vimentin and S-100 protein. On the contrary, as compared to jaw myxoma, the normal developmental structures were immunonegative for S-100 protein but stained for vimentin. These results could indicate a difference in the derivation other than tooth mesenchyma. PMID- 1594484 TI - Aneurysms of the carotid arteries associated with von Recklinghausen's neurofibromatosis. AB - Aneurysms of both common carotid arteries were seen in a patient with neurofibromatosis. Histologic examination of the involved arteries demonstrated a dense proliferation of spindle cells within the arterial walls accompanied by medial cystic degeneration and disruption of the tunica elastica. These changes were also observed in adjacent, grossly uninvolved segments of the blood vessels. Immunohistochemical analysis of the proliferating cells was positive with antibodies against desmin and muscle-specific actin. The findings demonstrate and confirm the smooth muscle origin of the aberrant proliferated cell population in arteries in a patient with von Recklinghausen's neurofibromatosis. PMID- 1594485 TI - Cytonuclear morphometry in the assessment of dysplasia in colorectal adenomatous polyps. A pilot study. AB - In order to objectify the degree of dysplasia, results of nuclear and cellular morphometry were compared with assessed grades of dysplasia in 32 colorectal adenomatous polyps. Of these adenomas 8 showed mild, 17 moderate and 7 severe dysplasia (according to blind duplicate assessments by two pathologists). Using a microscope video-overlay interactive digitizing measurement system, 100 nuclei were measured in each specimen according to a strict measurement protocol. In a stepwise discriminant analysis the best discriminating features appeared to be mean stratification index, N/C ratio, mean contour ratio and mean form AR. Overall with these features 65.6% correct jackknifed classification of the 32 cases could be achieved. On the other hand, a clear three-group distinction could not be obtained, even with the best set of discriminating features. Similarly to gastric dysplasia, the morphometric features might be used to design a two-grade (low, high) rather than a three-grade system to assess the degree of dysplasia. These findings make clear that objectifying the degree of dysplasia in adenomatous polyps is possible by means of interactive morphometric analysis. PMID- 1594486 TI - Five types of pyloric cells in the antral mucosa of the stomach. AB - Only one type of pyloric cells in the exocrine antral glands is usually described in the literature. The review of 100 gastrectomy specimens revealed 5 types of pyloric cells: one composed of "ordinary" pyloric cells (i.e. cuboidal cells with ill-defined borders, pale, bubbly cytoplasm with an inconspicuous cytoplasmic network). The second type was characterized by pyloric cells with a small, regular vacuole, usually in a subnuclear position. The vacuole in such cells was negative for mucous stains. The third type of pyloric cells had a large intracytoplasmatic vacuole. Cells with this characteristic were found in cystically dilated pyloric glands. The vacuoles in such cells were usually negative for mucous stains although a rim of PAS or alcian blue positive substance was found in some vacuoles. The fourth type of pyloric cells had eosinophilic granules in the cytoplasm. These granules were proven to contain lysozyme. The fifth type had a non-vacuolated, homogeneous ("glassy") cytoplasm which was weakly positive for PAS but negative for acid mucins or mannosides. While the significance of the various types of pyloric cells herein described remains unclear, their easy identification in H & E stained preparations would permit more elaborated studies with histochemistry, immunohistochemistry and/or transmission electron microscopy in the future. PMID- 1594487 TI - Adeno-carcinoid or amphicrine tumors of the middle ear a new entity? AB - The clinicopathological, ultrastructural and immunohistochemical characteristics of four primary tumors of the middle ear are reported. These neoplasms showed a striking, heterogeneous aspect ranging from solid-trabecular (Type I) to tubulo glandular (Type II) growth patterns. Secretory activity of the tumor cells was evaluated by immunohistochemistry and electron microscopy. Based on these procedures, three cell types were found, mainly limited to tumors with a tubulo glandular (Type II) growth pattern. Most frequent were B-cells with an abundant pale cytoplasm containing neuroendocrine granules, both cytokeratin and vimentin as well as several endocrine marker substances. Less frequent were A-cells, which are slender, darkly staining and line the glandular lumina. They showed exocrine activity only and stained strongly with a polyclonal cytokeratin antibody. Finally, least frequent were amphicrine cells, which were characterized by both lumina and neuroendocrine granules in their cytoplasm and were interpreted as the link between A and B cells. Although this morphological description closely resembles that of carcinoids and adenocarcinoids of the respiratory tract and gut, the clinical behaviour of these middle ear tumors nevertheless seems different, with no recurrence or metastasis after a follow-up of 1 to 14 years (median 78 months). Therefore, some authors suggest that these tumors should be classified as middle ear adenomas or adenomatous tumors. However, we strongly feel that these tumours represent a distinct entity and can be classified as adenocarcinoids or amphicrine tumors, i.e. demonstrating both exocrine and endocrine activities. Further work is required to evaluate the exact proportion of neuroendocrine and amphicrine tumors in the heterogeneous group of adenomas and in the rarely described group of adenocarcinomas. PMID- 1594488 TI - Characterization of bone forming cells in posttraumatic myositis ossificans by lectins. AB - Lectins were used to characterize bone forming cells in posttraumatic myositis ossificans. The lectins applied were as follows: Arachis hypogaea (PNA): specific for beta-D-galactose (1,3)N-acetyl-D-galactosamine (Gal-1,3 GalNac), Canavalia ensiformis (Con A): specific for alpha-D-glucose (D-Glc) and alpha-D-mannose (D Man) and Wheat germ (WGA): specific for N-acetyl(1,4)D-glucosamine (Glc-NaC) and neuraminic acid. The development of myositis ossificans was characterized by the appearance of a WGA binding cell population. The lectin-binding sites appeared as a cluster in the supranuclear cytoplasm, corresponding to the Golgi-complex. However, the WGA lectin-binding sites disappeared in the mature form of myositis ossificans. We assume that these lectin binding cells may be the bone marrow derived precursors of myofibroblast-like cells which are responsible for bone formation within the damaged muscle. PMID- 1594489 TI - Human fatal yellow fever. Immunohistochemical detection of viral antigens in the liver, kidney and heart. AB - An immunohistochemical method to detect yellow fever antigen was developed using immune sera from rabbits and hamsters and hyperimmune ascitic fluid from mice. A search for the antigen was carried out in liver, kidney and heart in three fatal cases of yellow fever. In the liver it was present in the cytoplasm of hepatocytes, Councilman bodies and Kupffer cells. Yellow fever antigen was also detected in renal tubular epithelium and in groups of myocardial fibers. These findings suggest that viral replication occurs at sites other than the liver. Since yellow fever shares many features with other haemorrhagic fevers the use of immunohistochemistry can impart a significant improvement in the accuracy of its histopathological diagnosis. PMID- 1594490 TI - Epithelial and melanoma antigens in gliosarcoma. An immunohistochemical study. AB - Gliosarcomas are mixed tumors with malignant glial and mesenchymal elements. The number of GFAP-positive tumor cells decreases with the increase of sarcomatous components, until whole areas may be GFAP negative. These distinct differentiations may, however, lead to false interpretations in small tissue samples. In this connection, it is of interest that, according to other reports, glial tumors may be positive for different anti-keratin antibodies and this prompted us to undertake a systematic investigation of the immunoreactivity of gliosarcomas using a panel of well-characterized monoclonal antibodies against cytokeratins (KL1, AE 1/3, Lu-5, CK-19, CK MNF 116 and Ma-903). These cases were further studied with the anti-epithelial non-cytokeratin antibodies EMA, HEA 125, Ber-EP4, CEA as well as the melanoma-antibody HMB-45, Leu-M1, GFAP and vimentin. As screening study we examined 20 cerebral metastatic carcinomas, 21 malignant gliomas (including 6 gliosarcomas) and 3 metastatic melanomas with the monoclonal antibodies KL1 and HMB-45. All cerebral metastatic carcinomas and 4/6 gliosarcomas were positive for KL1, whereas all melanomas, 2 metastatic carcinomas and 3 gliosarcomas showed an immunostaining with HMB-45. All gliosarcomas were positive with at least one of the tested anti-cytokeratin antibodies. The gliosarcomas did not show an immunoreaction in any of the cases when CEA, HEA 125, Ber-EP4, EMA or Leu M1 were applied. In our opinion, the monoclonal antibodies HEA 125 and Ber-EP4 could obviously be helpful in differentiating gliosarcomas from metastatic carcinomas. PMID- 1594491 TI - Intranodal "amianthoid" myofibroblastoma. Report of six cases immunohistochemical and electron microscopical study. AB - Six cases of intranodal amianthoid myofibroblastomas are reported. Immunohistochemically the tumors were actin positive and S-100 protein and desmin negative. Intracytoplasmatic, actin-rich bodies, previously found to be a characteristic feature of this tumor, were identified as cytoplasmatic extensions filled with microfilaments at an ultrastructural level. Abortive vessel formation by the tumor cells and the proliferation of tumor cells centered on veins outside the capsule of the tumor in two of our cases indicated a close relationship between the intranodal palisaded myofibroblastoma and the musculature of vascular origin. PMID- 1594493 TI - Aggressive "breast-like" adenocarcinoma of vulva. AB - A case of vulvar adenocarcinoma seen in a 42-year-old woman is reported. The tumor involved the right labium majus and diffusely spread into the surrounding soft tissues as well as the inguinal lymph nodes and was histologically composed of nests, cords, and tubular formations recalling an aggressive duct carcinoma of breast. Likewise, tumor cells exhibited positivity for common breast tumor markers, such as epithelial membrane antigen, carcinoembryonic antigen, and glandular keratins. The possible origin of the neoplasm from mammary ectopic tissue in vulva or from vulvar skin adnexa is briefly discussed. PMID- 1594492 TI - Influence of trypsin-induced acute pancreatitis on survival and energy state of isolated acinar cells from rat pancreas. AB - To study the development of acute pancreatitis after intraductal trypsin instillation, at 4 hours, 1, 2, 4 and 6 days after this treatment and after instillation of physiologic saline viable acinar cells were isolated from rat pancreas. Gross anatomic and histologic findings were used to evaluate the time course of pathomorphologic changes. The isolated cells were incubated at 37 degrees C in Eagle's medium in a shaking water bath and the time course of their damage was studied. Additionally, by means of the active accumulation of the fluorophore rhodamine 6 G alterations of the mitochondrial membrane potential, an important parameter of the cellular energy metabolism was evaluated. The most severe histological damage was seen 1 and 2 days after trypsin instillation. At the same time yield and survivability of cells isolated, and their mitochondrial membrane potential reached a minimum. In the controls the time course of these parameters was very similar, but their decrease was less pronounced. Since a direct action of trypsin on acinar cells cannot be responsible for the findings presented a possible involvement of inflammatory cells and their products in the alteration of the cells and of their energy metabolism must be considered. PMID- 1594494 TI - Acinic cell carcinoma with primary presentation in an intraparotid lymph node. AB - A rare case of a poorly-differentiated acinic cell carcinoma with primary presentation in a hyperplastic intraparotid lymph node, is reported. As the tumour mainly consisted of ductular and undifferentiated cells growing in solid cords, diagnosis was rendered difficult. Typical acinic cells were only rarely observed. In the multiple sections reviewed a single tumour nodulus occurred in salivary gland tissue outside the lymph node capsule. The possibility of a microscopic clinically occult primary acinic cell carcinoma that metastasized and presented primarily in an intraparotid lymph node, is mentioned. A multifocal origin in salivary tissue within and outside the intraglandular lymph node is another assumption, which is discussed. Differential diagnoses are mentioned and results of immuno- and histochemical studies are reported. PMID- 1594495 TI - What's new in the pathology of neuronal cytoskeleton: the significance of neurofibrillary tangles. AB - Neurofibrillary tangles are a neuronal change observed in various conditions, linked with dementia when affecting the cerebral cortex as in Alzheimer's disease. They may be found locally close to fibrous or vascular tumors, or affect extensive regions of the neocortex while the cerebellum and the medulla are not affected. Recent immunological and biochemical studies demonstrate that the MT associated protein tau is the main component of the tangles, in an abnormally phosphorylated state. A consequence of the formation of tangles is a decreased assembly of MT in axons and dendrites, with disturbances of neuroplasmic flow. The relations between tangles and amyloid, as seen in Alzheimer's and Down's diseases are topographical, tangles accumulating in particular in neurites close to the amyloid in the senile plaques (but also at distance in cell bodies and neurites). Genetically and biochemically A4 or beta-amyloid and tau differ. The exact relation between the beta-pleated proteins of tangles and amyloid remain poorly understood. PMID- 1594496 TI - What's new in exogenous osteomyelitis? AB - By the increase in road and occupational accidents during the past few decades posttraumatic osteomyelitis has become not only the most important type of exogenous but of all inflammatory bone processes. The major morphologic, bacteriologic and immunologic studies about posttraumatic bone inflammation will be outlined in this survey. The histologic classification of chronic osteomyelitis has proved useful for the observation of the course and for the selection of the treatment in 1,500 patients. Detailed morphological studies have shown that posttraumatic osteomyelitis often begins with a necrosis of the outer tangential lamella of the tubular bone partly promoted by partial periosteal retrogression, possibly followed by a necrosis of the fracture ends caused by a disturbance of the medullary blood circulation. Type and extent of osteomyelitis are determined by several traumatic, therapeutic and endogenous factors. Bacteriologically an infection with staphylococcus aureus is still prevailing. Comparative studies about the causative agents shortly after the trauma and during the following osteomyelitis have basically shown an identical range of causative agents. Immunologic studies with monoclonal antibodies in the actual site of inflammation have on the one hand found a decrease in the number of T lymphocytes and the T-helper cells and on the other hand an increase in the T suppressor cells, natural killer cells, macrophages in the osteomyelitic site. The impact of these findings on the therapy of osteomyelitis can presently not be estimated. However, they will become important after immunohistochemical studies of the bone and soft tissue Lager in osteosynthetic material after aseptic bone surgery have been carried out.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594497 TI - Tyrosine kinase activity of epidermal growth factor receptor in human gastric carcinomas. AB - We examined tyrosine kinase activity of epidermal growth factor (EGF) receptor in a total of 34 human gastric carcinomas as well as in non-neoplastic gastric mucosa from the same patients. EGF receptor kinase activity of the carcinoma tissues and the non-neoplastic mucosa were 1.28 +/- 1.00 (Mean +/- S.E.) and 0.16 +/- 0.04 respectively, if the EGF receptor kinase activity of human placenta is 10. Twenty-one (62%) carcinoma tissues showed higher EGF receptor kinase activity than corresponding non-neoplastic mucosa, while in 6 cases (18%) the kinase activity was higher in the non-neoplastic mucosa than in the tumor tissues. No obvious correlation was observed between the increased kinase activity in the tumors and histological type or tumor staging. One tumor showed extremely high receptor kinase activity with ERBB gene amplification. This tumor showed strong immunoreactivity to EGF itself. PMID- 1594498 TI - Discrimination of pancreatic adenocarcinomas from chronic pancreatitis by morphometric analysis. AB - Chronic pancreatitis and pancreatic ductal adenocarcinoma show similar gross and microscopic anatomical features. Morphological examination alone is not always sufficient in diagnostic practice to make the clinically important discrimination between these two entities. Cases of pancreatic tumors were analysed in a morphometric study to evaluate the discriminatory value of nuclear and nucleolar features. Histologic sections of pancreas from 18 cases of chronic pancreatitis and 33 cases of ductal adenocarcinoma were included either into a learning or a test set. A multivariable discriminatory rule was derived from the learning set of 23 cases including nuclear polymorphism and nucleolar density. When applied to the test set, all 28 cases of adenocarcinomas and chronic pancreatitis were correctly classified. Distributional features describing nucleolar density and variation in nuclear size and shape were the most efficient discriminatory variables. Morphometry is shown to be a simple and fast cell analytical method which can support clinical judgement in distinguishing between chronic pancreatitis and pancreatic ductal adenocarcinoma. PMID- 1594499 TI - Gastric heterotopia in the gallbladder. Case report and review of literature. AB - We report a case of gastric heterotopia in the gallbladder of an 18-year-old man. Symptoms of acute cholecystitis are characteristic in patients under 20 years old, while older patients present with chronic cholecystitis and gallstones. The heterotopic mucosa results either in a mass, a polyp, or a multiloculated gallbladder. Twenty-eight other cases of gastric heterotopia in the gallbladder or cystic duct have been reported. In only three was it associated with peptic ulceration. Treatment is cholecystectomy. Heterotopic gastric mucosa has been described throughout the length of the gastrointestinal tract from the oral cavity to the rectum. Curiously, it is extremely rare in the gallbladder, where it has the propensity for causing symptoms of acute cholecystitis, particularly in the young. We report a case of this condition in which there was a separate loculus lined by gastric epithelium. PMID- 1594501 TI - Mast cell frequency in soft tissue tumors. Relation to type and grade of malignancy. AB - A high content of mast cells (MC) is considered characteristic of neurofibromas but not of malignant schwannomas and neurilemmomas. We examined the extent and reliability of this finding by counting MC in 61 peripheral nerve sheath tumors and in 103 non-neurogenic soft tissue sarcomas. We furthermore investigated correlations between the amount of MC and various features of the tumors (e.g. grades of malignancy). Neurofibromas had very high mast cell counts. However, this result only applied to about 70% of these tumors. Malignant schwannomas, malignant fibrous histiocytomas and leiomyosarcomas had remarkably high median values of MC counts with a wide dispersion within the histological groups. Synovial sarcomas were the only group that contained MC in every case, though often in small numbers. In univariate analyses the number of MC was negatively correlated to grades of malignancy, cellularity and mitotic activity of the sarcomas and tended to correlate positively to the amount of myxoid and collagenous connective tissue and lymphocytic infiltrates. Multiple linear regression analysis revealed a significant correlation to the grade of malignancy and the amount of connective tissue. PMID- 1594500 TI - De novo expression of aromatase in gastric carcinoma. Light and electron microscopic immunohistochemical and immunoblot study. AB - We have performed immunohistochemical and immunochemical studies of steroidogenic enzymes involved in estrogen biosynthesis in 30 cases of gastric carcinoma in order to investigate possible in situ production of estradiol (E 2) in carcinoma cells. Positive incidence of immunoreactivity for E 2, testosterone (T), cholesterol side-chain cleavage enzyme (P-450 scc) and aromatase (P-450 arom) were 17/30 (56.7%), 11/30 (36.7%), 3/30 (10.0%) and 23/30 (76.7%), respectively on light microscopy. Estrogen receptor (ER) immunoreactivity was not observed in any of the 30 cases examined. Normal gastric mucosa was negative for P-450 arom and P-450 scc. Examination of serial sections revealed that immunoreactivity of E 2 and P-450 arom were located in the same cells of carcinomatous glands. Immunoelectron microscopy demonstrated that E 2 and P-450 arom were located along the membrane and cisternae of smooth endoplasmic reticulum (sER). Western blot analysis showed one major band of 55 kDa of P-450 arom in the gastric carcinoma tissues examined. Retrospective analysis of immunohistochemistry of E 2 in 108 cases of gastric carcinoma revealed that E 2 positive carcinoma cases were likely to demonstrate better survival rate than negative cases. These results above strongly suggest that E 2 is produced by de novo expressed aromatase in gastric carcinoma cells and is possibly involved in the biology of gastric carcinoma cells. PMID- 1594502 TI - The expression of CEA, CA 19-9 and HMFG antigens in ovarian clear-cell and endometrioid carcinomas. AB - The tumour antigen expression of ovarian and endometrial endometrioid carcinomas, ovarian clear-cell carcinomas as well as endometrial and cervical clear-cell carcinomas were immunohistochemically compared. Of special interest were potential differences between the endometrioid and clear-cell carcinomas of the ovary. The expression of CEA and CA 19-9 tumour antigens in all these tumour types was heterogeneous, with 10-20% of the cases being positive for CEA and 40 75% being positive for CA 19-9. In contrast, HMFG IIIC 12, a monoclonal antibody originally directed against human milk fat globule (HMFG) membrane antigens, invariably detected a corresponding antigen on every case of these tumour types. Another HMFG antibody, SM IF 3, on the other hand, detected antigenic material on all clear-cell tumour types, but only rarely on endometrioid tumours of the ovary or endometrium. While HMFG IIIC 12 detects an antigen present on all ovarian, endometrial and mammary carcinomas, antibody SM IF 3 thus appears to be more restricted in its staining patterns. Our results with both of these antibodies indicate that ovarian clear-cell carcinomas and ovarian endometrioid carcinomas have antigenic differences, which provides further evidence that they belong to different tumour entities. PMID- 1594503 TI - Primary non Hodgkin's malignant lymphoma of the vagina. Report of 3 cases with review of the literature. AB - Twenty cases of primary non-Hodgkin's malignant lymphoma (ML) of the vagina were studied: the 17 cases reported in the literature, and 3 further cases observed at the Hotel-Dieu Hospital in Paris over the last 10 years. The mean age of the women was 49 years. The most frequent complaint was vaginal bleeding, only a few patients presented an ulcerated mass. No evidence of ML was seen on any of the cervico-vaginal cytologic smears. Diagnosis was made on the vaginal biopsy. According to the Kiel classification, 8 of these ML were of low malignancy and 12 of high malignancy. Apart from one of our cases, which was an angiocentric pleomorphic T ML with predominance of medium-sized cells, they were all B ML. According to the Ann Arbor staging system for extra-nodal ML, 12 of these ML were stage IE, 2 were stage IIE and 2 other stage IVE. Eight patients died, 6 of ML less than 17 months after diagnosis, 2 much later of diseases unrelated to ML. The mean follow-up period of patients who survived, free of disease, was 75 months. The surgical treatment has to be limited, associated with polychemotherapy and completed by local radiotherapy. PMID- 1594504 TI - Mast cells in granulomatous liver disease. AB - Mast cells are known to be present in normal liver tissue but the data on their association with diseases of the liver are limited. In this study we used a long toluidine blue technique to investigate the mast cell numbers in 20 normal and 45 diseased liver biopsies containing granulomas (20 tuberculosis, 14 sarcoidosis, 4 schistosomiasis, 4 neoplasia-associated, 3 drug idiosyncrasy). Our results show that the mast cells are regular constituents of normal portal tracts and the amount of mast cells in the diseased samples corresponds to the area occupied by non-parenchymal tissues. As compared to normal controls, significantly less mast cells were present in biopsies from tuberculosis patients (p less than 0.025). Highest numbers were found in the schistosomiasis group. No link between the mast cell numbers and the cause of the granulomas could be demonstrated. PMID- 1594505 TI - Viral hepatitis: A, B, C, D and E--infection. PMID- 1594506 TI - Managing patients with asthma: the pediatrician as emergency physician, chronic illness specialist, and teacher. PMID- 1594507 TI - Pelvic inflammatory disease in adolescents. PMID- 1594508 TI - Chronic physical disorders. PMID- 1594509 TI - Developmental dyslexia: an update. PMID- 1594510 TI - Inheritance of blood ring, an early embryonic failure in the turkey. AB - Blood ring describes an early embryonic failure that has been observed in a subline of Wrolstad Medium White turkeys. The condition can be detected by candling at approximately 96 h of incubation when shell pigmentation is minimal. The condition, macroscopically visible as early as 66 h, is characterized by the presence of uncoalesced blood islands, an erythrocyte-engorged sinus terminalis, and the absence of an extra-embryonic circulatory system. The sex ratio of progeny from the mating of heterozygous parents did not deviate from a 1:1 ratio and no blood ring embryos resulted from the matings of heterozygous males and normal females. The disorder is inherited as an autosomal recessive trait and appears to be similar to a condition observed in both normal-sized and dwarf (dw) Single Comb White Leghorn chickens. The symbol blr is suggested for the gene. PMID- 1594511 TI - Correlated responses in lines of chickens divergently selected for fifty-six-day body weight. 1. Growth, feed intake, and feed utilization. AB - Correlated responses for growth, feed intake, and feed utilization were measured in female chickens from lines after 32 generations of divergent selection for 56 day body weight and in sublines in which selection had been relaxed for five generations. The diet used in the present experiment was that under which selection had been practiced (20% crude protein and 2,685 kcal of ME/kg). Feed intake between each selected line and its relaxed subline was equalized by paired feeding. Ad libitum-fed controls were also maintained. At 21 days of age, differences between the selected lines for ad libitum-fed chickens were 404% for body weight, 279% for feed intake, and 138% for feed conversion ratio (FCR). Respective percentages for the high and low relaxed lines under ad libitum feeding were 267, 223, and 121%. When pair-fed, the growth of the line selected for high weight was unimpeded and FCR improved. When chicks of the low-weight relaxed line were pair-fed, FCR also improved, but growth was reduced and appetite development inhibited. Hyperphagic behavior was observed in the line selected for high weight. In the low-weight selected line, the chicks exhibited hypophagia. Although residual feed consumption was unchanged by selection for 56 day body weight, variation was present for this trait, with lower values under restricted than ad libitum feeding. PMID- 1594512 TI - The effect of temperature, dietary energy level, and corn particle size on broiler performance. AB - Experiments were conducted to study the effect on broiler performance of grinding corn with different hammer mill screen openings (HMSO). Corn for Trials 1 and 2 was ground through HMSO of 3.18 or 9.59 mm and broilers were grown at 15.5 and 26.6 C in Trial 1 and at 26.6 C in Trial 2. Dietary energy levels used from 22 to 42 days were 3,050 and 3,230 kcal ME/kg for Trial 1 and 3,230 and 3,330 kcal ME/kg in Trial 2. In all starter and finisher diets, lysine and sulphur amino acid concentrations were similar on a megacalorie basis. In Trials 3 and 4, HMSO were 3.18, 4.76, 6.35, and 7.94 mm. Corn ground through a HMSO of 9.59 mm significantly reduced body weight and feed:gain ratio in Trials 1 and 2 at 21 days as compared with corn ground through an HMSO of 3.18 mm. At 42 days, body weights were reduced when corn was ground through 9.59- and 3.18-mm HMSO for the starter and finisher diets, respectively, as compared with those fed with the corn ground through a 3.18-mm HMSO in the starter diet. In Trials 3 and 4, significant differences in body weight and feed:gain ratios at 21 days were not noted for feed containing corn ground through an HMSO of 3.18, 4.76, 6.35, or 7.94 mm. PMID- 1594513 TI - A mathematical model for estimation of broiler egg weight loss from physical dimensions and air cell size during incubation. AB - A formula was derived that will enable hatcheries to estimate percentage weight loss using the width, length, and air cell diameter of the egg. The formula was derived by fitting an equation to the shape of the egg and using this shape equation to obtain estimates of air cell volume and egg volume. These estimates were coupled with the principle that weight = density x volume to give the final formula as a function of air cell diameter divided by egg width. The formula was tested by comparing its estimated values with measured values from eggs set at two different incubation conditions chosen to cover the range of conditions found in commercial hatcheries. As the day of transfer approached, embryo size and distortion of the air cell caused inaccuracies to develop in the results of this equation. However, data suggest that the equation can be used to calculate percentage weight loss until approximately the 16th day of incubation. PMID- 1594514 TI - Introduction: applied ethology and poultry science. AB - As a scientific discipline, the study of the biological basis of behavior in animals, ethology, is comparatively new. Ethologists have traditionally conducted primarily observational studies designed to ascertain the evolutionary significance of behaviors in wild animals. There is, however, a growing branch of ethology that is concerned with the application of ethological principles to areas such as the management and welfare of economically important species like poultry. Because of the complexity of the causation and expression of behaviors in animals, it is particularly important that such studies be rigorously designed and analyzed. The purpose of this symposium was to stimulate interest in the study of poultry behavior and welfare, and to provide information about current methodology in ethology. PMID- 1594515 TI - Applications of behavior to poultry management. AB - The application of poultry behavior to management is discussed with examples of behavior-management interactions relating to commercial poultry husbandry practices. Behaviors that are important for the adaptation of poultry to husbandry include: social behavior, aggression, sexual behavior, feeding, broodiness, cannibalism, nest site selection, and comfort behaviors. PMID- 1594516 TI - Sampling methods in behavior research. AB - Animals perform a continuous stream of behavior throughout their lives. Because their behavior is not random, appropriate sampling methods can be used to obtain data that accurately reflect the actual behavior and are valid for answering research questions. Answering questions related to several variables assists in narrowing the choices of sampling methods. First, a determination must be made of what behaviors to measure. If the behaviors are few and easily measured, then All Occurrences Sampling is the method of choice because it generates accurate frequency and duration data through continuous recording. Sequence and Sociometric Matrix Sampling are specialized types of All Occurrences Sampling that are restricted to sampling intra- or interindividual sequences and social interactions (e.g., agonistic), respectively. Second, if who (e.g., specific individual, sex, or genotype) performs the behavior is a major component of the research question, then consideration should be given to Focal Animal (Pair, Group) Sampling. Third, if when or where the behavior is performed is of interest (e.g., activity budget), then Instantaneous or Scan Sampling can often be effective. Ad libitum Sampling does not produce valid data for analyses, but it is useful when formulating and fine-tuning research questions. One-Zero Sampling is not recommended except when the research question relates to the presence or absence of behaviors only. Other factors to consider in selecting a sampling method are duration of the behavior (event or state), desired scale of measurement (nominal, ordinal, interval, or ratio), and logistics (e.g., time, and equipment and facilities available). PMID- 1594517 TI - Measuring social behavior in poultry. PMID- 1594518 TI - Measuring preferences and the strength of preferences. AB - In this review, it is argued that welfare concerns what animals feel. Preference tests give a good first indication of how animals feel and are therefore extremely valuable in animal welfare studies. Methods of overcoming the shortcomings of preference tests are discussed. In order that the results from preference tests be interpreted properly, they should be followed up with appropriate tests to measure the strength of preference. Examples of research in this area that have focused on poultry are given. PMID- 1594519 TI - Response of early- and late-maturing commercial Leghorn pullets to low levels of dietary phosphorus. AB - An experiment with a 2 x 2 factorial arrangement of treatments was used to determine differences in responses of early-maturing (EM) and late-maturing (LM) pullets fed low dietary P (.4% total P; LP) and normal dietary P (.7% total P; NP) levels. Six hundred pullets (18-wk-old) were equally and randomly allocated to the LP and NP treatments. Egg production, egg weight, egg specific gravity, and eggshell breaking strength were measured at 26 and 28 wk. When pullets were 28 wk of age, plasma total Ca (TCa), ionic Ca (Ca++), and inorganic P (Pi) concentrations, urine Ca concentrations, and urine pH, bone mineral content (BMC), bone density, total kidney weight, and kidney weight ratio (heavier kidney divided by lighter kidney) were determined from 15 pullets each from EM-NP, EM LP, LM-NP, and LM-LP treatments. The pullets with osteoporosis and pullets that died during the experiment were categorized into EM and LM groups. Results showed that LP caused severe adverse effects on LM pullets. The LM pullets fed the LP diet had high plasma Ca++ concentration, low plasma Pi concentration, increased urine Ca concentration, a high incidence of osteoporosis, mild kidney lesions, and elevated mortality compared with pullets subjected to the other treatments. The EM pullets fed the LP diet were also adversely effected by LP, but were less susceptible to osteoporosis and mortality. The LP diet improved eggshell quality, but this beneficial effect was only temporary. The severity of adverse effects of low dietary P was greater for LM than the EM pullets. PMID- 1594520 TI - Capacity in the liver of the broiler chick for conversion of supplemental methionine activity to L-methionine. AB - The objective of the present experiments was to determine whether the levels of supplemental methionine sources currently used in practical diets exceed the capacity of the chick to convert the supplement to L-methionine. Supplemental sources examined included DL-2-hydroxy-4-(methylthio(butanoic acid (DL-HMB, Alimet, or MHA) and DL-methionine (DL-Met). Two approaches were taken: first, the amount of enzyme activity available for conversion of the two supplemental methionine sources was determined using optimum reaction conditions for each and chick liver homogenate as the enzyme source. These experiments showed that total liver enzyme conversion activity was 564 mumol/h for DL-HMB and 529 mumol/h for DL-Met. The total activities for the two sources were not different when measured at saturating substrate concentration. Second, to address the question of whether the enzyme is limiting for either source under practical feeding conditions, birds were fed starter diets supplemented with DL-HMB or DL-Met at .25% of the diet for 3 wk. When hepatic levels of free HMB and methionine were determined, birds fed DL-HMB contained 7.6 nmol HMB/g of liver and 84.7 nmol methionine/g of liver. Birds fed DL-Met had levels of 7.6 nmol HMB/g liver and 80.3 nmol methionine/g liver. These results indicate no accumulation of HMB or DL-Met, which might occur if conversion capacity were saturated. By calculation, a bird consuming 100 g/day of a diet supplemented with .25% activity would need to convert about 70 mumol/h, indicating a sevenfold excess of enzyme in the liver alone. PMID- 1594521 TI - The scientific way to pigment poultry products. Introduction to the symposium. PMID- 1594522 TI - Chemical and physiological behavior of feed carotenoids and their effects on pigmentation. AB - Feed carotenoids are not inert substances. In the metabolism of animals, they may undergo a large number of transformations. A number of these compounds have vitamin A activity. Those that have high vitamin A activity usually have fairly low pigmenting properties. Generally only monohydroxy- and monoketocarotenoids are converted into vitamin A. Generally plants synthesize optically active carotenoids. The laying hen is not able to transform all carotenoid configurations so that they can be used to increase egg pigmentation. Feed carotenoids occur in natural compounds in about 60 to 90% trans and 10 to 30% cis form. The trans form is a more effective pigment because of the redder hue and greater stability. Either the hen has the ability to convert some of the trans form into the cis form, or this transformation occurs in the egg yolk. The saponification process improves the digestibility of certain xanthophyll preparations. The efficiency of fat absorption in the hen also influences the deposition rate. PMID- 1594523 TI - The use of high-performance liquid chromatography for studying pigmentation. AB - The use of HPLC has established that chickens possess unexpected metabolic abilities to acylate, deacylate, reduce, and oxidize carotenoids. The use of HPLC permits more consistent and more economic pigmentation of carcasses and of egg yolks. Hopefully, the use of HPLC will raise pigmentation from an art to a science. Apparently, HPLC will be an essential tool in terms of future efforts to understand and master the process of poultry pigmentation. PMID- 1594524 TI - Methodology for achieving pigment specifications. AB - The methodologies for poultry pigmentation are varied and often are not well coordinated. Differences in the ability to measure pigments, as opposed to appearance, have resulted in systems designed to deliver enough pigment to the bird based on experience in achieving and maintaining acceptable product appearance. Through the application of HPLC techniques, however, feed ingredients can be analyzed and diets can be formulated to extremely precise levels; but the effects on the final product can only be measured in gross and vague terms. New developments in computer-aided scanning and imaging systems may allow for an effective evaluation of the complex surface appearance presented by a broiler carcass and can relate subtle differences in feed formulation to the ultimate appearance of the poultry product. PMID- 1594525 TI - Origin and impact of color on consumer preference for food. AB - There are great differences among species in the way pigment is deposited on the skin or in the egg yolk. Xanthophyll-type compounds produce the color. Consumers have associated a yellow color with a normal state of health. Many consumers insist on the color and indicate that increased cost is not much of a deterrent. At present, increasing the pigmenting properties of a poultry feed increases costs from $5 to $15/ton. Pigmentation is more costly in the fish industry and may increase the cost of the diet up to or over $100/ton, especially in the final 20% of the feed consumed before processing. The pigmentation should be consistent and uniform in both species. A history of high-pigment broilers is presented. High-pigment broilers lend themselves to effective television advertising. PMID- 1594526 TI - Effect of oxygen and maternal dietary iodine on embryonic carbohydrate metabolism and hatchability of turkey eggs. AB - Fertile turkey eggs were produced by hens fed supplemental iodine to decrease eggshell conductance. The eggs were then incubated in an oxygen-enriched environment during Days 25 and 26 of incubation to test the hypothesis that maternal dietary iodine has separate effects on the eggshell permeability and the developing embryo. Oxygen supplementation improved hatchability regardless of dietary iodine treatment, suggesting that oxygen availability may limit hatching of eggs with normal gas conductance. Oxygen and dietary iodine did not affect body weight but interacted prior to pipping to affect embryonic liver and heart glycogen. Dietary iodine increased liver glycogen at internal pipping. The effects of oxygen on embryos, which were correlated directly with hatchability, were increased liver growth prior to pipping and increased heart weight at external pipping and posthatching. It was concluded that supplementing oxygen to incubating turkey eggs may improve hatchability by increasing liver and heart growth. Dietary iodine played only a minor or modulating role in assisting embryos to survive. PMID- 1594527 TI - Effect of modifications of semen diluent with cell culture serum replacements on fresh and stored turkey semen quality and hen fertility. AB - Two commercially available serum replacements formulated as supplements to somatic cell culture media were used with a turkey semen diluent to determine their effect on semen quality and spermatozoal fecundity before and after semen storage for 24 h. Progressive motility estimates (visual) and spermatozoal motility characteristics estimated by a computer-assisted semen analysis system, and sperm viability tests (the ethidium bromide exclusion procedure and a sperm stress test) were used to evaluate the semen. Although the presence of the serum replacements significantly increased spermatozoal motility, fertility was not augmented by the presence of the serum replacements. Computer-derived spermatozoal velocity and the percentage of nonviable spermatozoa estimated by the sperm stress test were negatively correlated with hen fertility. It was concluded that although the serum replacements augmented some spermatozoal motility characteristics, they failed to improve the fecundity of spermatozoa either before or after semen storage for 24 h. PMID- 1594528 TI - Lactic acid fermentation of broiler processing waste: physical properties and chemical analyses. AB - Broiler processing waste (offal), consisting of broiler heads, viscera, and feet, was collected from a commercial processing plant, ground, mixed with a fermentable substrate, and inoculated with actively growing organisms from a commercial silage culture. The offal mixture was fermented at 11, 19, and 37 C for up to 48 h and evaluated for pH, odor, and aqueous, solid, and oil fractions produced by centrifugation. Freshly ground offal, fermented offal, and aqueous and solids fractions were analyzed for moisture, fat, and protein content. The oil fraction produced by centrifugation of the fermented offal was analyzed for fatty acid composition. The optimum fermentation conditions, as determined by final pH, were obtained by the addition of 6% sucrose, inoculation with 10(6) cfu of silage culture organisms/kg of offal, and incubation at 37 C. The pH decreased from 6.2 to 3.9 in 24 h. Freshly ground offal and 48-h fermented offal were found to contain 63.2% moisture, 15.9% fat, and 14.9% protein, and 57.3% moisture, 19.1% fat, and 12.9% protein, respectively. The aqueous and solid fractions were 73.3% moisture, 1.1% fat, and 12.1% protein, and 57.7% moisture, 6.8% fat, and 21.8% protein, respectively. Fermentation was effective in decreasing pH, altering the odor and viscosity, and, upon centrifugation, increasing fat recovery and producing fractions that were easily separated. PMID- 1594529 TI - Research note: performance of single comb White Leghorn pullets as influenced by niacin supplementation from zero to six weeks of age and subsequent layer performance. AB - Two experiments were conducted using a total of 288 Hy-Line W-36 day-old Single Comb White Leghorn (SCWL) pullets in each experiment. The pullets were randomly assigned to one of the six dietary treatments that consisted of 0, 1.5, 3.0, 6.0, 12.0 or 36.0 mg supplemental niacin/kg in a corn and soybean meal basal diet that contained 25.1 mg niacin/kg. Six replicates of eight pullets per replicate were used per treatment in each experiment. Feed and water were provided for ad libitum consumption. The pullets were housed in battery brooder pens with raised wire floors. Total feed consumption (FC), BW, BW gain, and feed efficiency (FE) were measured at 3 and 6 wk of age. Birds were observed daily for any signs of niacin deficiency. At the end of a 6-wk experimental period, the pullets that previously received the diets containing either 0 of 36.0 mg supplemental niacin/kg of diet were raised to sexual maturity (SM) and their age at SM, BW at 24 wk, and number of eggs per pullet through 36 wk were measured in both experiments. No differences (P less than .05) in FC, BW, and FE were observed from 0 to 3 or 3 to 6 wk. None of the birds showed any signs of deficiency during the experimental period. No differences were observed in SM, number of eggs laid, and BW at 24 wk. It was concluded from these experiments that SCWL pullets do not require more than 25.1 mg/kg niacin furnished by the corn and soybean meal diet from 0 to 6 wk. PMID- 1594530 TI - Research note: effect of removing salt from the diet of broiler breeder hens. AB - Two 28-day experiments were conducted utilizing 75-wk-old Arbor Acres broiler breeder hens to determine the effect of removing salt from the diet. Birds in Experiment 2 had been force-rested at 60 wk of age but were in production (65% hen-day) at experiment initiation. All hens received a corn-soybean meal diet either with or without added salt. Egg production was significantly reduced in both experiments by the end of the 4th wk for birds fed the diet with no added salt. However, egg production did not cease in hens receiving the diet with no added salt. Egg weights from hens receiving the diet with no added salt were significantly reduced by the end of Week 2 in Experiment 1 and Week 3 in Experiment 2. Specific gravity was only intermittently affected by dietary salt removal. Birds receiving no added salt lost 541 and 580 g in Experiments 1 and 2, respectively. Birds receiving added salt diets gained 55 and 23 g in Experiments 1 and 2, respectively. Removing salt from the diet was not an acceptable method of force-resting broiler breeder hens. PMID- 1594531 TI - Suicidal inactivation of human cytochrome P-450 by carbon tetrachloride and halothane in vitro. AB - A significant loss of human cytochrome P-450 was observed during the anaerobic incubation of NADPH-reduced human liver microsomes obtained from surgical samples, in presence of carbon tetrachloride or halothane. In order to prevent any interference in the classical spectrum of cytochrome P-450 with CO, the method of Johannesen & DePierre (1978) was modified to obtain cytochrome P-450 determination. The enzyme inactivation reaction showed pseudo-first order kinetics and was accompanied by destruction of the haem tetrapyrrolic structure, as indicated by a significant loss of its porphyrin fluorescence. Values of about 200 and 700 were calculated for the partition ratio between metabolic turnover of the substrate and enzyme inactivation during reductive incubation of one of these microsomal preparations with limiting concentrations of CCl4 and halothane, respectively. The results indicate that human liver cytochrome P-450 can be inactivated reductively in vitro by CCl4 and halothane reactive metabolites and suggest that a suicide type of mechanism, similar to that which was recently demonstrated to occur, for both substrates, with rat liver microsomes (Manno et al. 1988a & 1991), may also be involved in the inactivation of the human enzyme(s). PMID- 1594532 TI - Acute and long term effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in tests of nociception in mice. AB - Acute and long term changes in nociception after administration of 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) 80 mg/kg (four injections of 20 mg/kg given at two hr intervals) were investigated in mice. MPTP caused shivering, lacrimation, salivation, teeth chattering and fur erection a few minutes after drug injection, but all these behavioural changes were normalized within 30 min., when the first behavioural testing was performed. No significant alteration in general behaviour, sensorimotor performance or body temperature could be detected at the time of nociceptive testing. The acute effects of MPTP on nociception were a reduced response latency in the tail flick test and a prolonged response latency compared to controls in the constant temperature hot plate test. No significant effects of MPTP were found in the increasing temperature hot plate test. The long term effects were a reduced response latency both in the tail flick test and the constant temperature hot plate test, indicating that the MPTP induced lesions of dopaminergic pathways result in hyperalgesia. In the increasing temperature hot plate test and the formalin test, no significant long term changes were demonstrated. Seven days after injection, the dopamine content was reduced to 62% of control values in striatum, to 51% in the rest of the forebrain, and to 41% in the spinal cord. Noradrenaline levels were only slightly and transiently reduced. Serotonin levels were not affected 7 days after injection, but 14 days after injection, a great increase was found in the forebrain and in the spinal cord. The results suggest that dopaminergic systems tonically inhibit nociception.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594533 TI - Multiple-dose sodium polystyrene sulfonate in lithium intoxication: an animal model. AB - Previous work in our laboratory has demonstrated that sodium polystyrene sulfonate (SPS) significantly lowered serum lithium (Li) concentrations when administered in a single oral dose after an oral dose of lithium in a mouse model. The present study was designed to determine whether: 1) repetitive doses of SPS are effective in lowering serum lithium concentrations, 2) the effect of SPS on lithium concentration is dose related and 3) SPS enhances the elimination of lithium. Mice (N = 144) were given orogastric LiCl (250 mg/kg) and then divided into 4 groups: Controls received water 0, 30, 90, 180, and 360 min. after LiCl; the Full-Dose SPS Group received SPS (5 g/kg/dose) at equivalent times; the Half-Dose SPS Group received SPS (2.5 g/kg/dose) at the same times; and the Elimination Group received water at 0 and 30 min. after LiCl and SPS at 90, 180 and 360 min. after LiCl. Subgroups of each group were sacrificed at 1, 2, 4 and 8 hr post-treatment and serum analyzed for lithium concentrations. Statistical analyses revealed that, when compared to Controls: 1) SPS significantly lowered serum lithium concentrations; 2) this effect was dose-related; 3) repetitive dosing of SPS appears to enhance the elimination of lithium. PMID- 1594534 TI - Clinical responses in relation to blood acetaldehyde levels. AB - A study was undertaken to examine the relationship between blood acetaldehyde levels and clinical responses in volunteers receiving the anti-alcohol drugs disulfiram and calcium cyanamide. In the first part of this study volunteers received different doses of disulfiram (125 mg and 500 + 250 mg), of calcium cyanamide (25 mg, 50 mg and 100 mg) and of ethanol (0.2 g/kg orally and 0.5 g/kg intravenously). The ensuing interactions ranged from no reaction at all to an intense hypotensive cyanamide-ethanol reaction (CER). A blood acetaldehyde concentration-effect relationship was suggested. In the second part of this study seven subjects received 50 mg of calcium cyanamide 4 hr prior to an intravenous ethanol dose of 0.2 g/kg. The maximum blood level of acetaldehyde ranged from 16 to 241 microM. Aversive interactions started to occur at acetaldehyde levels around 40-60 microM. Changes in flushing reaction and diastolic blood pressure appeared best to reflect changing blood acetaldehyde levels. As a rule, however, the expected cyanamide-ethanol and disulfiram-ethanol reactions are more clearly registered as an increase in acetaldehyde levels than as the ensuing physiological responses. PMID- 1594535 TI - Influence of osmolarity of solutions used for K+ contraction on relaxant responses to pinacidil, verapamil, theophylline and terbutaline in isolated airway smooth muscle. AB - Concentration-relaxation profiles for pinacidil, verapamil, terbutaline and theophylline were studied in guinea-pig trachealis contracted by two commonly applied techniques for K+ depolarization. All drugs were much less effective on contractions induced by hyperosmolar 124 mMn K+ solution (added KCl) than on contractions elicited by an isoosmolar 124 mM K+ Krebs solution (substituted KCl). The maximal relaxant responses were (isoosmolar K+/hyperosmolar K+): pinacidil 100%/40%, verapamil 100%/60%, theophylline 100%/0%, terbutaline 50%/0%. Addition of mannitol to establish the same hyperosmolarity as with 124 mM KCl also produced contraction of guinea-pig trachealis. Concentration-relaxation curves for the drugs on mannitol-induced contractions had close resemblance to those obtained in hyperosmolar 124 mM K+ solution. When contraction was elicited by 30 mM K+, pinacidil showed seven times higher relaxant potency in hyperosmolar compared to isoosmolar solution, whereas the relaxant responses to verapamil, theophylline and terbutaline were not influenced by osmolarity. When K+ depolarization is used as a tool for evaluation of drug action in airway smooth muscle, the two different techniques produce dissimilar results. The influence of hyperosmolarity per se appears to be an important and unwanted feature when K+ depolarization is produced by addition of KCl. PMID- 1594536 TI - Preferential stimulation of locomotor activity by ventral tegmental microinjections of (-)-nicotine. AB - In the present study the effect of acutely administered (-)-nicotine on locomotor activity was measured after direct bilateral microinjections into the nucleus accumbens (Acb) or into the ventral tegmental area (VTA) of rats. Intrategmental (-)-nicotine (either 0.02 or 2 micrograms/side) increased locomotor activity, the effect being greatest after the lower dose. The stimulation began almost immediately and was shortlasting with peak activity occurring at 30 min. After injection. Intra-accumbal (-)-nicotine (either 0.02, 2 or 20 micrograms/side) caused only a marginal short enhancement of activity which was not dose dependent. The time course of enhanced activity was similar to that observed after intrategmental injection. Our results indicate that the nicotine-induced hyperlocomotion may arise primarily from activation of VTA nicotinic cholinoceptors (nAchRs), whereas activation of the accumbal nAchRs is less significant in regard to this effect. PMID- 1594537 TI - Intestinal absorption of inorganic mercury in rat. AB - 203Hg-Mercuric chloride was administered intragastrically to female rats. The absorption rate evaluated for a broad range of doses was found constant for low and medium range, and higher for high doses. Mercury was determined in internal organs and intestines. The time-course of intestinal mercury indicated that a deposit formed initially in the mucosa was further absorbed into the circulation. No indication was found of a protection mechanism based on exfoliation of the mucosal deposits of metal. PMID- 1594538 TI - A method for simultaneous evaluation of drug-effects on excitability and inotropy in isolated cardiac preparations. AB - A method is described which allows determination of the threshold of excitability of electrically stimulated, regularly contracting isolated cardiac preparations. The force of the contraction (CF) is isometrically recorded and serves as feed back signal indicating effective stimulation. The pulse intensity is decreased monoexponentially as long as contractions are elicited. If the mechanical response does not occur, the pulse intensity is immediately reset to the initial high value and the pulse is delivered with a latency of a few milliseconds. A stimulus intensity just below threshold is recorded as the rectangular pulse threshold (RPT). The method was applied in order to compare the effects of a number of antiarrhythmic drugs including the beta-blocker propranolol on the electrical excitability (1/RPT) and on the contractility of guinea pig left atria stimulated at 3 Hz. In general, the drugs depressed excitability and contractility concomitantly. The rank order of potency with respect to the reduction of excitability was: aprindine greater than propafenone greater than propranolol greater than quinidine greater than mexilitine greater than lidocaine. The Ca-antagonist verapamil reduced contractile force most powerful but had no effect on excitability. Presumably, RPT reflects sodium-channel function. In conclusion, the described method offers an easily operable test of drug effects on the excitability threshold and the contractility of isolated cardiac preparations. PMID- 1594539 TI - Effects of noradrenaline and prostaglandin F2 alpha on angiotensin-induced contraction and tachyphylaxis in rat aortic rings. AB - The aim of this study was to examine the effects of noradrenaline (NA) and prostaglandin F2 alpha (PGF2 alpha) on angiotensin II (AII)-induced contraction and tachyphylaxis in aortic rings of the rat. Neither NA (10(-9) M) nor PGF2 alpha (10(-7) M) had significant effect on the response of the rings to the spasmogenic concentrations (10(-10) to 10(-7) M) of AII, but lowered significantly the threshold response of the aortic rings to AII (from 10(-9) to 10(-12) M). In rings that were tachyphylatic to AII, both NA and PGF2 alpha attenuated significantly the tachyphylaxis of the rings to AII at the concentrations of 10(-10) and 10(-7) of the octapeptide; and also lowered the threshold of the tachyphylatic rings to AII (from 10(-9) to 10(-11) M for NA, and from 10(-9) to 10(-10) M for PGF2 alpha). The specific properties of noradrenaline and PGF2 alpha were not shared by the non-specific potassium chloride. Because the lowering of threshold and attenuation of tachyphylaxis occurred at the physiological levels of AII and NA, it is possible that the in vivo actions of AII are under constant modulation by circulating and localised (higher than circulating) levels (e.g. of PGF2 alpha) of spasmogens. The results also call into question the physiological significance of angiotensin tachyphylaxis and may suggest that it is only an in vitro phenomenon occurring in the absence of endogeneous spasmogens. PMID- 1594540 TI - Effect of a NSAID which does not inhibit cyclooxygenase on cerebral level of PGE2 in rat experimental brain oedema. PMID- 1594541 TI - Effect of interaction between lead and ethylenediamine on digoxin-induced cardiac arrest in isolated frog heart. PMID- 1594542 TI - Serotonin receptors in the brain of rats treated chronically with lithium administered via the food or by intraperitoneal injections. PMID- 1594543 TI - [Specificity of action of extracellular proteases from Streptomyces spp]. AB - The ability of an Actinomyces strain--Streptomyces spp. to produce extracellular proteases has been studied under varied cultivation conditions during the growth cycle. The activity of enzyme preparations precipitated from the culture liquid was determined with various substrates--gelatin, casein, fibrinogen, fibrin and collagen. The isolated enzyme complex possessed caseinolytic, fibrinolytic, thrombolytic and collagenolytic activities. PMID- 1594544 TI - [A comparative study of the effect of pyrazole on the activity of enzymes in the alcohol/polyol dehydrogenase family]. AB - A comparative study of the effect of pyrazol, an inhibitor of the coenzyme binding site of alcohol dehydrogenases, on the activity of enzymes of the alcohol/polyol dehydrogenase group has been carried out. Commercial preparations of alcohol dehydrogenases from the cytoplasm of horse liver cells and yeast cells, as well as the enzyme from the cytoplasm of Trichosporon pullulans cells was completely inhibited by 1 mM pyrazol, while alcohol dehydrogenases from Candida utilis and Saccharomyces carlsbergensis were inhibited only by 25% and the enzymes from Saccharomyces cerevisiae and Torulopsis candida by 30 and 38%, respectively. The inhibition degree of alcohol dehydrogenases from the cytoplasm of liver cells of various mammals (bull, calf, rat, gopher) and birds (hen, pheasant, duck) varied from 12 to 42% in the presence of 1 mM pyrazol. The activity of sorbitol dehydrogenase from the liver cytoplasm of these mammals and birds changed neither in the presence of 1 mM pyrazol, nor in the case of a 15 fold increase of the inhibitor concentration. Possible structural differences in the coenzyme-binding site of the active center of the enzymes under study are discussed. PMID- 1594545 TI - [New principles of ion exchange preparative chromatography and their applications for isolation, purification and super purification of antibiotics]. AB - New types of structurally segregated heteronetwork biosorbents with given parameters of heterogeneity and porosity have been developed. Physico-chemical characteristics of the biosorbents on the basis of which one can predict optimal structures of ion exchangers to be used in preparative chromatography of biologically active compounds were studied. A new principle of sequential displacement of ions of organic compounds, in particular antibiotics, adsorbed on selective biosorbents with a high adsorption capacity was developed, which enables purification and superpurification of the desired compound. The method is based on the effect of small thermodynamic shifts in physico-chemical parameters of the elution system, which results in preparative separation of substances with close properties and in purification of the desired compound from microadmixtures. The "small shift effect" is realized in the case of limiting thermodynamic and kinetic parameters of heterogeneous mass exchange and with biosorbents possessing a highly selective adsoprtion capacity. PMID- 1594546 TI - [Yeast superoxide dismutase: isolation and properties (review of the literature)]. AB - Modern data are reviewed on isolation procedures and properties of superoxide dismutase from Saccharomyces cerevisiae. Properties of superoxide dismutase (SOD) from yeast and SOD from macro-organisms were compared. PMID- 1594547 TI - [Stabilization and protection of an enzymatic system, participating in the transformation of beta-carotene into retinal, during its isolation]. AB - The authors studied the effect of dithiothreitol (DTT), carotenoids and protease inhibitors on stabilization and protection of the enzyme catalysing the conversion of beta-carotene into retinal during the enzyme isolation from the rabbit small intestine. The addition of 1 mM DTT into the homogenization mixture increased the activity of the enzyme 5 times compared with control. The additional introduction of 0.7 mg/ml soybean trypsin inhibitor or 2.10(-4) M phenylmethylsulfonyl fluoride increased the enzyme activity 2.1 and 1.2 times, respectively. Lutein, beta-carotene and lycopene at a concentration of 10 mg/ml increased the enzyme activity 2.1, 1.9 and 1.6 times respectively. The effects of DTT, lutein and the protease inhibitor depended on their concentrations and was of an independent additive character. The maximum activity of the isolated enzyme exceeded the control without DTT 15 times. PMID- 1594549 TI - Ultrastructure of the guinea pig pancreas in acute hypercalcemia. AB - The effect of acute hypercalcemia on pancreatic ultrastructure and the ultrastructural localization of calcium during hypercalcemia were studied in the guinea pig pancreas. After 3 h of i.v. calcium infusion (0.6 mmol/kg/h), hypertrophy and distention of the Golgi apparatus and an increased number of condensing vacuoles were seen. At 6 h, vacuolar fusion and displacement of zymogen granules occurred. At 9 h, irregular distribution of zymogen granules, indentation of the nucleus with chromatin clumping, and inclusion of intact cell organelles were present. Disruption of the plasma membrane and release of cell organelles into the interstitial space were seen. Control animals receiving saline solution (0.9% NaCl) revealed normal pancreatic ultrastructure. The serum ionized calcium values were 0.65 +/- 0.36 mM in controls and 0.71 +/- 0.14, 0.79 +/- 0.21, and 1.22 +/- 0.50 mM at 3, 6, and 9 h of calcium infusion, respectively. The ultrastructural localization of calcium was performed with the pyroantimonate staining technique after 3 h of calcium and saline infusion. Large calcium deposits were found in calcium-treated animals along the plasma membrane and in the Golgi region. The findings indicate that calcium exerts a strong stimulatory effect that eventually leads to the degeneration of the pancreatic acinar cell. PMID- 1594548 TI - Stimulation of DNA synthesis in pancreatic duct cells by gastrointestinal hormones: interaction with other growth factors. AB - Pancreatic duct cells of the Syrian hamster were grown as monolayers on thin layers of type I collagen coated onto microporous membranes. The effects of a number of potential trophic factors were tested by their ability to increase [3H]thymidine incorporation into cellular DNA. To measure the effect of growth factors, cells were subjected to a period of growth factor depletion to induce a state of partial quiescence in DNA synthesis. Cells responded with a significant increase in thymidine incorporation after the addition of epidermal growth factor (EGF) alone or a growth factor mixture containing EGF plus insulin, transferrin, selenium, linoleic acid, bovine pituitary extract, triiodothyronine, and dexamethasone. When the serum substitute, Nu Serum IV (5%, vol/vol), was added to this mixture, addition of several gastrointestinal (GI) hormones including secretin, vasoactive intestinal polypeptide (VIP), bombesin, and gastrin caused significant increases in thymidine incorporation at concentrations of 0.01-1 microM. At 1 microM, these hormones stimulated DNA synthesis relative to their respective control in the order secretin (178%) greater than bombesin (153%) greater than VIP (138%) greater than gastrin (126%). Cholecystokinin octapeptide, a known trophic factor for pancreatic acinar cells, did not cause significant increases in thymidine incorporation in cultured duct cells. These results suggest that pancreatic duct cells possess receptors for a number of GI hormones and respond to the trophic effects of hormones known to stimulate pancreatic growth in vivo. PMID- 1594550 TI - Involvement of endogenous cholecystokinin in pancreatic regeneration after cerulein-induced acute pancreatitis. AB - This study was undertaken to determine the involvement of endogenous cholecystokinin (CCK) in the regeneration of pancreatic tissue after cerulein induced acute pancreatitis treated by the CCK receptor antagonist L364,718. Acute pancreatitis was induced in rats by s.c. injections of cerulein in gelatin (12 micrograms/kg) three times a day for 2 days with controls receiving saline in gelatin. Rats were then divided into four treatment groups: saline-dimethyl sulfoxide (DMSO) (SD), saline-L364,718 (SA), cerulein-pancreatitis-DMSO (CD), and cerulein-pancreatitis-L364,718 (CA). In the first experiment, rats were treated for 3 or 10 days with DMSO or L364,718 (0.1 mg/kg, twice a day). In the second experiment, rats were treated for 13 days with DMSO or L364,718 (1.0 mg/kg, twice a day). After the rats were killed, pancreata were weighed and evaluated for their total protein, amylase, chymotrypsin, RNA, and DNA. We found that destruction of the pancreatic tissue occurred after cerulein-induced pancreatitis and that regeneration of the tissue was in progress but incomplete after 10 days; the low dose of L364,718 did not prevent regeneration. After 13 days, regeneration was still incomplete but the 1-mg dose of L364,718 strongly inhibited spontaneous regeneration. These data suggest that endogenous CCK is an important and potent trophic factor in the regeneration process of pancreatic tissue following an episode of acute pancreatitis. PMID- 1594551 TI - Increased intragastric acid-resistant lipase activity and lipolysis in pancreatic steatorrhoea due to cystic fibrosis. AB - We measured gastric lipase activity and lipolysis in postprandial gastric samples from 10 adults with steatorrhoea due to cystic fibrosis (CF) and from 10 healthy volunteers of similar age and sex. Gastric samples were aspirated for 2 h following a meal consisting of emulsified long-chain triglyceride. Mean acid resistant lipase activity was twice as high in CF patients as in controls (596 vs. 299 nmol/ml/min fatty acid released; p = 0.028 for area under the curve). Lipolysis rose from 5 to 10% during the postprandial period in CF patients, compared with a constant 5% in controls (p = 0.036 for area under the curve). We conclude that, in healthy adults, lipolysis of long-chain triglyceride starts in the stomach, while in adults with pancreatic steatorrhoea due to CF, gastric lipase activity and intragastric lipolysis are increased, perhaps in compensation for pancreatic insufficiency. PMID- 1594552 TI - Therapeutic potential and clinical efficacy of acid-resistant fungal lipase in the treatment of pancreatic steatorrhoea due to cystic fibrosis. AB - We investigated the therapeutic potential of an acid-resistant fungal lipase prepared from Aspergillus niger. We first demonstrated in vitro that it had a wide pH optimum of 2.5-5.5 and was resistant to pepsin and trypsin. We gave the enzyme or matching placebo in random order by mouth with a fatty meal to 10 adult patients with pancreatic steatorrhoea due to cystic fibrosis (CF) and sampled gastric contents for the following 2 h. Mean acid-resistant lipase activity was 330 nmol/ml/min free fatty acid released on placebo, compared with 896 nmol/ml/min on fungal lipase (p = 0.006 for area under the curve). We compared this lipase's clinical efficacy with that of two conventional pancreatin microsphere formulations in an open randomised crossover fat-balance study in 10 similar patients. Each preparation was given for 2 weeks, and a fat-balance study, using a faecal recovery marker, was performed on the final 3 days; a period without treatment was also included. The fungal lipase had no effect on faecal wet weight or on the coefficient of fat absorption (59.0% vs. 52.3%; NS) in comparison with placebo. The established enteric-coated microsphere preparation (Creon) produced a significant reduction in faecal wet weight and improvement in coefficient of fat absorption (81.4% vs. 52.3%; p less than 0.01) in comparison with placebo. The newer microsphere preparation (Pancrex M) was also effective, but perhaps less so than Creon; there were no significant differences between the two preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594553 TI - Pancreatic phospholipase A2 in proximal tubules of rat kidney in experimental acute pancreatitis and after intravenous injection of the enzyme. AB - Kinetics and distribution of i.v. human pancreatic phospholipase A2 (h-PLA2) were determined in intact and nephrectomized rats, and tissue localization of rat pancreatic PLA2 (r-PLA2) was studied by immunohistochemistry in experimental acute pancreatitis. The concentration of h-PLA2 and the catalytic activity of phospholipase A2 in plasma decreased exponentially in intact and nephrectomized animals after the injection. The initial 15-min half-life was considerably longer in nephrectomized animals, and higher h-PLA2 concentrations and PLA2 catalytic activities were found in plasma. h-PLA2 was localized in endocytotic vesicles and apical cytoplasmic vacuoles in proximal tubule cells of the kidney. The intensity of the immunoreaction decreased considerably between 15 and 50 min in these cells. No signs of tubular damage were seen by light microscopy. Neither immunoreactive h-PLA2 nor PLA2 catalytic activity was found in urine. r-PLA2 was observed in proximal tubule cells 15 min after an injection of sodium taurocholate (necrotizing pancreatitis group) or saline (edematous pancreatitis group) into the pancreatic duct. Signs of tubular damage were present in necrotizing pancreatitis, but tubular morphology was normal in the animals with edematous pancreatitis. We conclude that the proximal tubule cells of the kidney participate in the metabolism of circulating pancreatic PLA2, and considerably higher PLA2 levels persist in plasma in nephrectomized animals. Endogenous pancreatic PLA2 is detected in kidneys in acute pancreatitis. PMID- 1594554 TI - Effect of soybean flour on exocrine function in rat pancreas transplant with bladder drainage. AB - The urinary output of trypsin, chymotrypsin, elastase, and amylase by rats with a pancreas transplant and bladder drainage was determined after injection with cholecystokinin (CCK) or by feeding diets containing high (raw soy flour) or low (heated soy flour) trypsin inhibitor activity. The injection of CCK produced a significant increase in the urinary output of all four enzymes. Rats were fed heated or raw soy flour in three consecutive 10-day periods in the following sequence: period 1, heated soy flour; period 2, raw soy flour; period 3, heated soy flour. Replacing heated soy flour in period 1 with raw soy flour in period 2 caused a significant increase in the output of the four enzymes. Subsequent feeding with heated soy flour in period 3 resulted in a reduction in the output of trypsin, chymotrypsin, and elastase to levels that were not significantly different from that observed in period 1. Although amylase output was also reduced in period 3, it did not return to the level noted in period 1. These results are consistent with the roles that CCK and trypsin inhibitors are believed to play in the negative feedback control of pancreatic exocrine function. A similar approach might be employed with humans who have undergone a pancreas transplant with bladder drainage. PMID- 1594555 TI - Role of the distal pancreas in pancreatic polypeptide release. AB - In two previous studies, postprandial pancreatic polypeptide (PP) release was inhibited when pancreatic denervation was combined with distal pancreatectomy. In contrast, postprandial PP release was unaffected by pancreatic denervation without a distal pancreatectomy. These findings suggested a role for the distal pancreas in regulation of postprandial PP release. To examine this possibility, we performed distal pancreatectomy on four mongrel dogs. Pancreatic polypeptide response to i.v. insulin (0.5 U/kg), a meal, and an infusion of cholecystokinin octapeptide (CCK-8; 50 ng/kg/h) were measured in conscious dogs before and after distal pancreatectomy. Insulin-induced hypoglycemia stimulated PP release both preoperatively (47.0 +/- 8.8 ng.[0-120]min/ml) and postoperatively (61.6 +/- 9.2 ng.[0-120]min/ml). Ingestion of a meal also evoked significant PP release preoperatively (85.8 +/- 22.1 ng.[0-180]min/ml) and postoperatively (105.8 +/- 42.2 ng.[0-180]min/ml). CCK-8 elicited only a small increase in circulating PP, which was not influenced by distal pancreatectomy. These findings demonstrate that distal pancreatectomy does not alter PP response to insulin, a meal, or CCK 8. PMID- 1594556 TI - Gastrin-releasing peptide: binding and functional studies in mouse pancreatic islets. AB - The binding of GRP (gastrin-releasing peptide) to mouse pancreatic islets was studied. Binding of 100 pM 125I-GRP to collagenase-prepared isolated islets at 22 degrees C was one-half maximal after 15 min and maximal at 60 min. At 60 min, total binding was 1.62% of total radioactivity per 50 islets; nonspecific binding (presence of 1 microM unlabeled GRP-1-27) was 0.05-0.61% of total radioactivity. GRP binds specifically to a high-affinity site (Kd1 = 0.81 nM; Bmax1 = 12.8 fmol/50 islets). The specific binding is saturable. Hormones with the intact C terminus of GRP-1-27, such as N-acetyl-GRP-20-27 and neuromedin C (GRP-18-27), possess the same inhibition curve as GRP-1-27. GRP-1-16, with a cleaved C terminus, does not inhibit binding of 125I-GRP. However, hormones that virtually are not structurally related to GRP, such as eledoisin, galanin, and VIP (vasoactive intestinal peptide) do not compete for GRP binding. The rank order of GRP analogs such as GRP-1-27, N-acetyl-GRP-20-27, and GRP-1-16 is similar though not identical with respect to inhibition of 125I-GRP binding and insulin secretory potency. We found that 1 and 10 nM GRP-1-27, at a stimulatory glucose concentration, increases the breakdown of phosphatidylinositol to Ins-1,4,5-P3, the biological relevant isomer of Ins-P3; 10 nM GRP-1-27 is effective even at a nonstimulatory glucose concentration in this respect. In a virtually Ca(2+)-free medium, 5 nM GRP-1-27 increases the 45Ca2+ efflux from 45Ca(2+)-prelabeled islets. These data indicate that (a) specific binding sites for GRP are present in mouse pancreatic islets; (b) GRP superimposes the maximal insulinotropic effect of glucose; and (c) Ins-1,4,5-P3 is probably involved as a second messenger in the biological effects of GRP-1-27, which is underlined by the efflux of Ca2+ from intracellular stores but is not a sufficient signal by itself. PMID- 1594557 TI - The relationship of islet amyloglucosidase activity and glucose-induced insulin secretion. AB - We have previously presented evidence for the involvement of islet acid amyloglucosidase, a lysosomal glycogen-hydrolyzing enzyme, in certain insulin secretory processes. In the present investigation, we studied whether differential changes in islet amyloglucosidase activity could be related to the insulin secretory response to glucose. It was observed that the dose-response curve for glucose-induced insulin response in vivo was shifted to the left by pretreatment of mice with purified fungal amyloglucosidase. In enzyme-pretreated mice, the ED50 was 2.1 mmol/kg glucose as compared with 5.7 mmol/kg in saline pretreated controls (p less than 0.005). Also, the maximal insulin response to glucose was enhanced by amyloglucosidase pretreatment. Parenteral administration to mice (four injections during 2 days) of the pseudotetrasaccharide acarbose, a recognized inhibitor of intestinal alpha-glucosidases, surprisingly induced a marked increase in the activities of islet acid amyloglucosidase (+ 120%; p less than 0.001) and acid alpha-glucosidase (+ 45%; p less than 0.01) without affecting the activities of other lysosomal enzymes such as acid phosphatase and N-acetyl-beta-D-glucosaminidase. No effect on the microsomal neutral alpha glucosidase was recorded. Moreover, in these mice, the insulin secretory response to glucose was enhanced both at a maximal dose of glucose 11.1 mmol/kg and at a dose in the ED25-ED50 range, 3.3 mmol/kg (p less than 0.005). Direct addition of acarbose to islet homogenates strongly suppressed acid amyloglucosidase activity, the EC50 being approximately 1 microM. Acid alpha-glucosidase activity was also strongly inhibited, whereas the activities of acid phosphatase and N-acetyl-beta D-glucosaminidase were unaffected. Neutral alpha-glucosidase was slightly suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594558 TI - Effects of endotoxin and interleukin-1 on glucagon and insulin secretion from the perfused rat pancreas. AB - This study evaluated the in vivo effects of endotoxin and interleukin-1 (IL-1) on the simultaneous secretion of glucagon and insulin. The hypothesis that endotoxin, or IL-1 as a mediator, induces hyperglucagonemia secondary to pancreatic hypersecretion of glucagon was examined. Hormone secretion was measured using the in vitro perfused rat pancreas preparation. In response to an arginine stimulus, glucagon secretion was neither stimulated nor inhibited significantly by endotoxin or IL-1. Insulin secretion was significantly potentiated with both endotoxin and IL-1. In response to a low-glucose stimulus, glucagon secretion was significantly inhibited by endotoxin treatment, while insulin secretion was increased by endotoxin or IL-1. These results indicate that neither endotoxin nor IL-1 treatment resulted in glucagon hypersecretion, although either of these agents could induce insulin hypersecretion. Thus, the mechanism of endotoxin-induced hyperglucagonemia cannot be explained by a hypersecretory state of glucagon secretion. The parallel respective effects of endotoxin and IL-1 on glucagon and insulin secretion are consistent with the concept that IL-1 mediates some of the effects of endotoxin on the endocrine pancreas. PMID- 1594559 TI - Pancreatic islets of obese hyperglycemic mice (ob/ob). AB - The development of the obesity-associated hyperglycemic syndrome in ob/ob mice, genetically determined, was observed over time by a combined functional and structural study of pancreatic islets. Islet areas increased with advancing age in ob/ob mice from 2 times at 1 month to 30 times at 6 months of age the size of lean mouse islets. Islet areas apparently increased more than pancreatic insulin content in ob/ob mice. Glucose and insulin tolerance tests were performed to study in vivo responses to glucose and insulin, respectively, in 1-, 3-, and 6 month-old mice. With ob/ob mice, glucose tolerance tests revealed more elevation of plasma glucose than in lean mice, the lean mice revealing more elevated plasma insulin than the obese mice. In insulin tolerance tests, lean mice presented marked hypoglycemia, whereas ob/ob mice revealed slightly higher plasma glucose at 1 month of age but three to four times higher amounts than that of lean mice at 6 months of age. Thus, increasing insulin resistance in ob/ob mice older than 3 months is associated with progressively increasing islet area, which contains proportionally less insulin than that of lean mouse pancreas. The data suggest that insulin resistance in ob/ob mice progressively develops up to 6 months of age and that marked islet hyperplasia is likely in response to sustained hyperglycemia, leading to hyperinsulinemia and eventual marked obesity. PMID- 1594561 TI - Repetitive cerulein-induced pancreatitis and pancreatic fibrosis in the rat. AB - The effect of repetitive inductions of pancreatitis by supramaximal doses of cerulein on pancreatic morphology and collagen content was studied in the rat. Pancreatitis was induced nine times at intervals of about 20 days; 3 days after the last injection of cerulein, pancreatitis was still observed, as indicated by pancreatic weight loss, increase of protein-bound hydroxyproline content, acinar cell destruction, cellular infiltration, and deposition of collagen fibers. However, 6 weeks later, no differences in the parameters mentioned above were observed between control and cerulein-treated animals. Thus, repetitive induction of pancreatitis in the rat, according to the experimental protocol we used, did not result in pancreatic fibrosis. PMID- 1594560 TI - Patterns of innervation of vasoactive intestinal polypeptide, neuropeptide Y, and gastrin-releasing peptide immunoreactive nerves in the feline pancreas. AB - In this study, we performed a detailed analysis of the immunoreactive (IR) patterns and tissue distribution of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) in the feline pancreas by means of immunohistochemical and radioimmunological techniques. Immunoreactivity for each peptide is localized to varicose nerve fibers distributed throughout the exocrine and endocrine pancreas, with some differences in the density and pattern of fiber distribution. In the acinar and stromal compartments, VIP-IR processes have a higher density than NPY- and GRP-containing fibers, the latter being the least abundant. The vasculature receives a particularly prominent NPY innervation, while GRP- and VIP-IR fibers are found occasionally in association with blood vessels. Around ducts, NPY- and VIP-IR nerves are more numerous than those positive for GRP-IR, which are quite sparse. One of the most interesting findings of the present work is the visualization of all peptide-IRs both in neuronal cell bodies and fibers within the intrapancreatic ganglia. VIP-IR is observed in virtually all ganglion cells, while GRP- and NPY-IRs are seen in a few neuronal cells. VIP and NPY tissue levels are much higher than GRP concentrations in all regions of the pancreas. VIP content in the head and body is greater than in the tail. The morphological relationship of VIP-, NPY-, and GRP-IR fibers with different pancreatic structures is consistent with specific peptidergic neural inputs in the regulation of pancreatic functions. PMID- 1594562 TI - Human Muc 1 mucin gene expression in the fetal pancreas. AB - The expression of the human Muc 1 mRNA was evaluated during fetal pancreatic development. Human fetal pancreatic tissues were collected at various stages from 13 to 24 weeks of age. Northern blot analysis of total RNA from these tissues showed that Muc 1 mRNA was not detectable until 18-19 weeks of age. Therefore, Muc 1 mucin expression can be detected in prenatal human pancreata at approximately 19 weeks of age and thereafter. PMID- 1594563 TI - Distal pancreatic atrophy and diabetes associated with an intrapancreatic hydatid cyst. PMID- 1594564 TI - Acute pancreatitis associated with hypercalcemia in a patient with multiple myeloma. PMID- 1594565 TI - A glucagonoma without necrolytic migratory erythema. PMID- 1594566 TI - Beta-sheet rearrangements: serpins and beyond. PMID- 1594567 TI - A data bank merging related protein structures and sequences. AB - A data collection which merges protein structural and sequence information is described. Structural superpositions amongst proteins with similar main-chain fold were performed or collected from the literature. Sequences taken from the protein primary structure databases were associated with the multiple structural alignments providing they were at least 50% homologous in residue identity to one of the structural sequences and at least 50% of the structural sequence residues were alignable. Such restrictions allow reasonable confidence that the primary sequences share the conformation of the tertiary structural templates, except in the less conserved loop regions. Multiple structural superpositions were collected for 38 familial groups containing a total of 209 tertiary structures; 45 structures had no superposable mates and were used individually. Other information is also provided as main-chain and side-chain conformational angles, secondary structural assignments and the like. Wedding the primary and tertiary structural data resulted in an 8-fold increase of data bank sequence entries over those associated with the known three-dimensional architectures alone. PMID- 1594568 TI - Building protein backbones from C alpha coordinates. AB - An automatic procedure for building polyalanine backbones from guiding alpha carbon positions is presented. Polyalanine backbones are built based on the geometric restraints of angle N-C alpha-C and the knowledge of main-chain dihedral angle distributions. A building module constructs a list of polyalanine backbones that follow exactly the C alpha trace. Then a selection module selects one backbone with the largest portion of phi-psi pairs in favoured regions. Several test cases on C alpha coordinates from X-ray refined structures give acceptable results. Less than 10% of the peptide planes are incorrectly built, and the result is not sensitive to random shift up to 0.5 A of C alpha coordinates. PMID- 1594569 TI - CD4 and CD8 may adopt a similar mode of binding to their MHC ligands. AB - A theoretical scheme is proposed by which the type-specific cell surface receptors of T-lymphocytes, CD8 and CD4, bind class I and II MHC proteins in a similar manner. The scheme has equivalent residues in the C'/C'' loop-C'' strand C''/D loop region in domain 1 of CD4 and CD8 alpha binding to equivalent residues in the C and D beta-strands and C/D loops in HLA-DR beta 2 (class II) and HLA-A2 alpha 3 (class I) respectively through a series of electrostatic, hydrogen and hydrophobic bonds. PMID- 1594570 TI - Introduction of a stabilizing 10 residue beta-hairpin in Bacillus subtilis neutral protease. AB - A 10 residue beta-hairpin, which is characteristic of thermostable Bacillus neutral proteases, was engineered into the thermolabile neutral protease of Bacillus subtilis. The recipient enzyme remained fully active after introduction of the loop. However, the mutant protein exhibited autocatalytic nicking and a 0.4 degree C decrease in thermostability. Two additional point mutations designed to improve the interactions between the enzyme surface and the introduced beta hairpin resulted in reduced nicking and increased thermostability. After the introduction of both additional mutations in the loop-containing mutant, nicking was largely prevented and an increase in thermostability of 1.1 degrees C was achieved. PMID- 1594571 TI - Increasing the thermostability of a neutral protease by replacing positively charged amino acids in the N-terminal turn of alpha-helices. AB - The 247-260 and 289-299 alpha-helices of Bacillus subtilis neutral protease have a lysine in their N-terminal turn. These lysines were replaced by Ser or Asp in order to improve electrostatic interactions with the alpha-helix dipole. After replacing Lys by Ser at positions 249 or 290, the thermostability of the enzyme was increased by 0.3 and 1.0 degrees C, respectively. The Asp249 and Asp290 mutants exhibited a stabilization of 0.6 and 1.2 degrees C, respectively. The results show the feasibility of stabilizing enzymes by introducing favourable residues at the end of alpha-helices. PMID- 1594572 TI - Structure-activity relationships in human interleukin-1 alpha: identification of key residues for expression of biological activities. AB - To identify the sites important for the different biological activities of human interleukin-1 alpha (hIL-1 alpha), 56 single-amino acid-substituted mutants of hIL-1 alpha were produced in Escherichia coli using site-directed mutagenesis, and were examined for their biological activities such as mouse lymphocyte activating factor activity (LAF activity), cytostatic activity against human melanoma cells A-375 (A375 activity) and prostaglandin E2 (PGE2) inducing activity in human osteosarcoma cells MG-63 (PEI activity). Two amino acid residues, Asp26 and Asp151, were found to be important for these activities. The replacement of Asp26 by Val caused a decrease in LAF and PEI activities by one or two orders of magnitude and a slight decrease in A375 activity. The Tyr or Phe substitution for Asp151 caused decreases in LAF and A375 activities by one or two orders of magnitude and complete loss of PEI activity. The change from Asp151 to Lys or Arg resulted in marked decrease in LAF activity and complete loss of A375 and PEI activities. Since Asp26 and Asp151 are close to each other in the three dimensional structure, the region involving these amino acids seems to be important for the biological activities of hIL-1 alpha. PMID- 1594573 TI - Site-directed mutagenesis of pseudoazurin from Alcaligenes faecalis S-6; Pro80Ala mutant exhibits marked increase in reduction potential. AB - Pseudoazurin (a blue copper protein or cupredoxin) of a denitrifying bacterium Alcaligenes faecalis S-6 is a direct electron carrier for a Cu-containing nitrite reductase (NIR) of the same organism. Site-directed mutagenesis of the pseudoazurin was carried out using an Escherichia coli expression system. Replacement of Tyr74 by Phe to remove an internal hydrogen bond in the beta barrel caused a slight decrease in heat stability as well as a requirement for a higher concentration of Cu2+ for production in the E. coli host. Exchange of Ala for Pro80 adjacent to His81, one of the four ligands binding a type I Cu atom, caused a marked increase in reduction potential by 139 mV without change in the optical absorption spectrum. The ability of the pseudoazurin to transfer electrons to NIR was markedly diminished but the apparent Km of NIR for pseudoazurin was not affected by the mutation. X-ray diffraction data collected on the oxidized and reduced forms of the Pro80Ala mutant show that a water molecule occupies the pocket created by the absent side chain. This observation suggests that the increase in reduction potential may be caused due to the increased solvent accessibility to the Cu atom. The electron density difference maps on these structures (at 2.0 A) show that this water moves during the change in oxidation state, and that there are small, but localized, conformational changes greater than 6.5 A from the copper site, as well as movement of both the Cu2+ and the cysteinate sulfur. PMID- 1594574 TI - The high-resolution crystal structure of porcine pepsinogen. AB - The structure of porcine pepsinogen at pH 6.1 has been refined to an R-factor of 0.173 for data extending to 1.65 A. The final model contains 180 solvent molecules and lacks density for residues 157-161. The structure of this aspartic proteinase zymogen possesses many of the characteristics of pepsin, the mature enzyme. The secondary structure of the zymogen consists predominantly of beta sheet, with an approximate 2-fold axis of symmetry. The activation peptide packs into the active site cleft, and the N-terminus (1P-9P) occupies the position of the mature N-terminus (1-9). Thus changes upon activation include excision of the activation peptide and proper relocation of the mature N-terminus. The activation peptide or residues of the displaced mature N-terminus make specific interactions with the substrate binding subsites. The active site of pepsinogen is intact; thus the lack of activity of pepsinogen is not due to a deformation of the active site. Nine ion pairs in pepsinogen may be important in the advent of activation and involve the activation peptide or regions of the mature N-terminus which are relocated in the mature enzyme. The activation peptide-pepsin junction, 44P-1, is characterized by high thermal parameters and weak density, indicating a flexible structure which would be accessible to cleavage. Pepsinogen is an appropriate model for the structures of other zymogens in the aspartic proteinase family. PMID- 1594575 TI - Substrate mobility in a deeply buried active site: analysis of norcamphor bound to cytochrome P-450cam as determined by a 201-psec molecular dynamics simulation. AB - While cytochrome P-450cam catalyzes the hydroxylation of camphor to 5-exo hydroxycamphor with 100% stereospecificity, norcamphor is hydroxylated by this enzyme yielding 45% 5-exo-, 47% 6-exo-, and 8% 3-exo-hydroxynorcamphor (Atkins, W.M., Sligar, S.G., J. Am. Chem. Soc. 109:3754-3760, 1987). The present study describes a 201-psec molecular dynamics (MD) stimulation of norcamphorbound cytochrome P-450cam to elucidate the relationship between substrate conformational mobility and formation of alternative products. First, these data suggest that the product specificity is, at least partially, due to the mobility of the substrate within the active site. Second, the high mobility of norcamphor in the active site leads to an average increase in separation between the heme iron and the substrate of about 1.0 A; this increase in separation may be the cause of the uncoupling of electron transfer when norcamphor is the substrate. Third, the active site water located in the norcamphorbound crystal structure possesses mobility that correlates well with the spin-state equilibrium of this enzyme-substrate complex. PMID- 1594576 TI - Functional significance of conserved amino acid residues. AB - A systemic study of single amino acid substitutions in bacteriophage T4 lysozyme permitted a test of the concept that conserved amino acid residues are more functionally important than nonconserved residues. Substitutions of amino acid residues that are conserved among five bacteriophage-encoded lysozymes were found to lead more frequently to loss of function than substitutions of nonconserved residues. Of 163 residues tested, only 74 (45%) are sensitive to at least one substitution; however, all 14 residues that are fully conserved are sensitive to substitutions. PMID- 1594577 TI - Comparative analysis of the beta transducin family with identification of several new members including PWP1, a nonessential gene of Saccharomyces cerevisiae that is divergently transcribed from NMT1. AB - While investigating the expression of the Saccharomyces cerevisiae myristoyl CoA:protein N-myristoyltransferase gene (NMT: E.C. 2.3.1.97) by Northern blot analysis, we observed another RNA transcript whose expression resembled that of NMT1 during meiosis and was derived from a gene located less than 1 kb immediately upstream of NMT1. This new gene, designated PWP1 (for periodic tryptophan protein), is divergently transcribed from NMT1 and encodes a 576 residue protein. Null mutants of PWP1 are viable, but their growth is severely retarded and steady-state levels of several cellular proteins (including at least two proteins that label with exogenous [3H]myristic acid) are drastically reduced. New methods for database searching and assessing the statistical significance of sequence similarities identify PWP1 as a member of the beta transducin protein superfamily. Two other previously unrecognized beta-transducin like proteins (S. cerevisiae MAK11 and D. discoideum AAC3) were also identified, and an unexpectedly high degree of sequence homology was found between a Chlamydomonas beta-like polypeptide and the C12.3 gene of chickens. A systematic and quantitative comparative analysis resulted in classifying all beta-transducin like sequences into 11 nonorthologous families. Based on specific sequence attributes, however, not all beta-transducin-like sequences are expected to be functionally similar, and quantitative criteria for inferring functional analogies are discussed. Possible roles of repetitive tryptophan residues in proteins are also considered. PMID- 1594578 TI - Deconvolution of the circular dichroism spectra of proteins: the circular dichroism spectra of the antiparallel beta-sheet in proteins. AB - A recently developed algorithm, called Convex Constraint Analysis (CCA), was successfully applied to determine the circular dichroism (CD) spectra of the pure beta-pleated sheet in globular proteins. On the basis of X-ray diffraction determined secondary structures, the original data set used (Perczel, A., Hollosi, M., Tusnady, G. Fasman, G.D. Convex constraint analysis: A natural deconvolution of circular dichroism curves of proteins, Prot. Eng., 4:669-679, 1991), was improved by the addition of proteins with high beta-pleated sheet content. The analysis yielded CD curves of the pure components of the main secondary structural elements (alpha-helix, antiparallel beta-pleated sheet, beta turns, and unordered conformation), as well as a curve attributed to the "aromatic contribution" in the wavelength range of 195-240 nm. Upon deconvolution the curves obtained were assigned to various secondary structures. The calculated weights (percentages determining the contributions of each pure component curve in the measured CD spectra of a given protein) were correlated with the X-ray diffraction determined percentages in an assignment procedure and were evaluated. The Pearson product correlation coefficients (R) are significant for all five components. The new pure component curves, which were obtained through deconvolution of the protein CD spectra alone, are promising candidates for determining the percentages of the secondary structural components in globular proteins without the necessity of adopting an X-ray database. The CD spectrum of the CheY protein was interesting because it has the characteristic shape associated with the alpha-helical structure, but upon analysis yielded a considerable amount of beta-sheet in agreement with the X-ray structure. PMID- 1594579 TI - Molecular modeling of an antigenic complex between a viral peptide and a class I major histocompatibility glycoprotein. AB - Computer simulation of the conformations of short antigenic peptides (5-10 residues) either free or bound to their receptor, the major histocompatibility complex (MHC)-encoded glycoprotein H-2 Ld, was employed to explain experimentally determined differences in the antigenic activities within a set of related peptides. Starting for each sequence from the most probable conformations disclosed by a pattern-recognition technique, several energy-minimized structures were subjected to molecular dynamics simulations (MD) either in vacuo or solvated by water molecules. Notably, antigenic potencies were found to correlate to the peptides propensity to form and maintain an overall alpha-helical conformation through regular i,i + 4 hydrogen bonds. Accordingly, less active or inactive peptides showed a strong tendency to form i,i + 3 hydrogen bonds at their N terminal end. Experimental data documented that the C-terminal residue is critical for interaction of the peptide with H-2 Ld. This finding could be satisfactorily explained by a 3-D Q.S.A.R. analysis postulating interactions between ligand and receptor by hydrophobic forces. A 3-D model is proposed for the complex between a high-affinity nonapeptide and the H-2 Ld receptor. First, the H-2 Ld molecule was built from X-ray coordinates of two homologous proteins: HLA-A2 and HLA-Aw68, energy-minimized and studied by MD simulations. With HLA-A2 as template, the only realistic simulation was achieved for a solvated model with minor deviations of the MD mean structure from the X-ray conformation. Water simulation of the H-2 Ld protein in complex with the antigenic nonapeptide was then achieved with the template-derived optimal parameters. The bound peptide retains mainly its alpha-helical conformation and binds to hydrophobic residues of H-2 Ld that correspond to highly polymorphic positions of MHC proteins. The orientation of the nonapeptide in the binding cleft is in accordance with the experimentally determined distribution of its MHC receptor-binding residues (agretope residues). Thus, computer simulation was successfully employed to explain functional data and predicts alpha-helical conformation for the bound peptide. PMID- 1594580 TI - Metal binding and folding properties of a minimalist Cys2His2 zinc finger peptide. AB - A minimalist Cys2His2 zinc finger peptide, Lys-Tyr-Ala-Cys-Ala-Ala-Cys-Ala-Ala Ala-Phe-Ala-Ala-Lys-Ala-Ala-Leu-Ala- Ala-His-Ala-Ala-Ala-His-Ala-Lys, has been synthesized. Metal binding studies using Co2+ as a probe indicated that this peptide forms a 1:1 peptide/metal complex with a dissociation constant comparable to that observed for other zinc finger peptides. At high peptide concentrations, a 2:1 peptide/metal complex also forms, with four cysteinates coordinated to Co2+. Additional studies with sequence variants in which the canonical hydrophobic residues were changed to alanine, or in which one of the residues between the cysteines and the histidines was deleted, revealed an even more pronounced formation of the 2:1 complex over the 1:1 complex. In addition, the absorption spectra of the 1:1 peptide/Co2+ complexes of the variant peptides are significantly different from those seen for complexes of the parent peptide or those of more typical zinc finger peptides. NMR studies revealed that the parent peptide folds in the presence of Zn2+ to a structure very similar to that observed for other zinc finger peptides of this class. Taken together, these results suggest that the metal-binding and canonical hydrophobic residues are necessary and sufficient to determine the structure of this class of zinc finger peptides. PMID- 1594581 TI - Mass determination and estimation of subunit stoichiometry of the bacterial hook basal body flagellar complex of Salmonella typhimurium by scanning transmission electron microscopy. AB - The basal body, a part of the rotary motor of the bacterial flagellum, is a multiprotein assembly that consists of four rings (denoted M, S, P, and L) and an axial rod (denoted R). From analysis of scanning transmission electron microscopy images of hook-basal body preparations isolated from Salmonella typhimurium, we have determined the masses of the basal body and three of its subcomplexes. The mass of the basal body (i.e., the four rings and rod) is 4400 +/- 490 kDa (mean +/- SD; n = 54). The mass of the LPR subcomplex (i.e., L and P rings and the whole rod) is 2600 +/- 380 kDa (n = 55), that of the L and P rings and the distal part of the rod is 2100 +/- 320 kDa (n = 25), and the mass of the L and P ring subcomplex is 1700 +/- 260 kDa (n = 514). These results, together with the masses of the component proteins, indicate that the rings contain approximately 26 subunits each and that the mass of the rod is consistent with a composition of approximately 6 copies each of three of the rod proteins FlgB, FlgC, and FlgF and approximately 26 copies of FlgG as determined by Jones et al. [Jones, C. J., Macnab, R. M., Okino, H. & Aizawa, S.-I. (1990) J. Mol. Biol. 212, 377-387] using quantitative gel electrophoresis. The results of Jones et al., together with ours, account for all proteins in the basal body to within approximately 5% (or 200 kDa). PMID- 1594583 TI - Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient. AB - In an investigation of the evolution of the third hypervariable loop of gp120 (V3), the principal neutralization determinant of human immunodeficiency virus type 1, we have analyzed 89 V3 sequences of plasma viral RNA purified from peripheral blood samples donated over 7 years by an infected hemophiliac. Considerable sequence diversity in the V3 region was found at all time points after seroconversion. Phylogenetic analysis revealed that an important diversification had occurred by 3 years postinfection and that, subsequently, most sequences could be allocated to either one of two major lineages that persisted throughout the remainder of the infection. Rapid changes in frequency of the most common sequences and the observation that the same hexapeptide motif (GPGSAV) at the crown of the V3 loop has evolved convergently provide strong evidence that selective processes determine the evolutionary fate of sequence variants in this region. PMID- 1594582 TI - Specific growth stimulation by linoleic acid in hepatoma cell lines transfected with the target protein of a liver carcinogen. AB - The hepatic carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) was shown previously to interact specifically with its target protein, liver fatty acid binding protein (L-FABP), early during hepatocarcinogenesis in rats. In search of the significance of the interaction, rat L-FABP cDNA in the sense and antisense orientations was transfected into a subline of the rat hepatoma HTC cell line that did not express L-FABP. After the transfections, the basal doubling times of the cells were not significantly different. However, at 10(-5)-10(-7) M, linoleic acid, which is an essential fatty acid, a ligand of L-FABP, and the precursor of many eicosanoids and related lipids, stimulated the incorporation of [3H]thymidine in three randomly isolated and stably transfected cell clones that expressed L-FABP, but virtually did not stimulate the incorporation of [3H]thymidine in three L-FABP-nonexpressing clones transfected with the antisense DNA. Linoleic acid at 10(-6) M increased cell number almost 3-fold (38% vs. 14%; P less than 0.0001) and thymidine incorporation nearly 5-fold (23.2% vs. 4.9%; P less than 0.001) in the L-FABP-expressing cells compared to that in the transfected nonexpressing cells. L-FABP acted specifically and cooperatively with linoleic acid, inasmuch as all the proteins other than L-FABP in the transfected L-FABP nonexpressing cells and four other fatty acids (gamma-linolenic acid, dihomo-gamma-linolenic acid, arachidonic acid, and palmitoleic acid) were unable to effect a significant elevation or difference in the level of DNA synthesis that was attributable to the transfection. Metabolism of the linoleic acid to oxygenated derivatives was apparently necessary, since the cyclooxygenase inhibitor indomethacin partly inhibited and the antioxidant lipoxygenase inhibitors nordihydroguariaretic acid and alpha-tocopherol completely abolished the growth stimulation. The evidence supports the idea that L-FABP, the target protein of the liver carcinogen, acts specifically in concert with oxygenated metabolites of linoleic acid to modulate the growth of hepatocytes. PMID- 1594584 TI - Rat p53 gene mutations in primary Zymbal gland tumors induced by 2-amino-3 methylimidazo[4,5-f]quinoline, a food mutagen. AB - There are reports of p53 gene mutations in various human cancers but not in rat tumor cell lines or rat primary tumor tissue. We found a p53 gene mutation in a cell line of a spontaneous squamous cell carcinoma of the rat Zymbal gland, SCC131, at codon 171 by direct sequencing of cDNA fragments amplified by PCR. We tested for p53 gene mutations in 15 primary Zymbal gland tumors induced by 2 amino-3-methylimidazo[4,5-f]quinoline by single-strand conformation polymorphism analysis of the PCR-amplified cDNA products. Samples of four tumors showed mobility shifts. Direct sequencing revealed that all these tumors had mutations in conserved regions or in scattered conserved residues. Single-strand conformation polymorphism analysis of cDNA suggested that mRNA from the wild-type allele of the p53 gene was not present in tumor cells of three of four positive cases, although genomic DNA analysis indicated that the wild-type allele was retained in all the cases. All mutations were found at a guanine base: three mutations were guanine----pyrimidine transversions and one was a deletion of a guanine base within a G+C-rich sequence. These findings indicate that 2-amino-3 methylimidazo[4,5-f]quinoline may be directly involved in induction of these mutations by forming DNA adducts at various sites in the p53 gene. PMID- 1594585 TI - Constitutive synthesis of tumor necrosis factor in the thymus. AB - Although tumor necrosis factor (TNF) is a major mediator of endotoxic shock, the normal function of TNF that has preserved this protein throughout mammalian evolution remains unknown. If the protein serves a role in normal development or homeostasis, it must be produced under physiologic conditions. To determine whether TNF secretion occurs in normal animals, and to define the tissue sources of the protein, we prepared a reporter construct in which the TNF coding sequence and introns are replaced by the chloramphenicol acetyltransferase (CAT) coding sequence. This construct was inserted into the murine genome, yielding 13 transgenic founders. Macrophages harvested from 4 of the transgenic lines expressed CAT activity after stimulation with Escherichia coli lipopolysaccharide in vitro. Each of these 4 transgenic lines also constitutively expressed CAT activity in the thymus but in no other tissue examined. Cultured thymocytes secrete TNF, as demonstrated both by cytotoxicity assays and by immunoprecipitation of radiolabeled thymic culture medium. CAT activity was associated with the thymic lymphocyte population and not with thymic macrophages or dendritic cells. CAT activity was present in thymic lymphocytes irrespective of CD4 or CD8 expression; T cells from the spleen, however, had no detectable CAT activity. The biosynthesis of TNF in the thymus of normal animals implies a role for this protein in the development or regulation of the immune response. PMID- 1594586 TI - Determination by systematic deletion of the amino acids essential for catalysis by ricin A chain. AB - The A chain of ricin is a RNA N-glycosidase that inactivates ribosomes by depurination of a single adenosine in 28S rRNA. Of the 267 amino acids in the protein, 222 (83%) could be deleted from one or another of 74 mutants without loss of the capacity of the protein to recognize a single nucleotide from among the 7000 in ribosomes or to catalyze hydrolysis. PMID- 1594587 TI - Loss of tumorigenicity of rat glioblastoma directed by episome-based antisense cDNA transcription of insulin-like growth factor I. AB - Malignant glioma is the most common brain tumor. The molecular basis of glioma tumorigenicity has not been defined. Cultured glioma cells accumulate high levels of insulin-like growth factor I (IGF-I) transcripts. We asked whether IGF-I expression is coupled to tumorigenicity, using a combined in vivo/in vitro system employing antisense RNA for IGF-I. An antisense IGF-I expression construct in an expression vector that incorporates Epstein-Barr virus replicative signals and the ZnSO4-inducible metallothionein I transcriptional promoter was assembled. Stable glioma transfectants were derived from C6 glioma cells, which constitutively express IGF-I. B-104 neuroblastoma cells, derived originally from the same tumor but not expressing IGF-I, were also transfected as controls. In the absence of ZnSO4, the C6 transfectants expressed high levels of IGF-I mRNA and protein as detected by in situ hybridization and immunocytochemistry, respectively. Addition of ZnSO4 in the culture medium resulted in high levels of antisense transcript accumulation and dramatically decreased levels of endogenous IGF-I mRNA and IGF-I protein. Subcutaneous injection of either nontransfected C6 parental cells or C6 cells transfected with vector without IGF-I sequences into rats resulted in large tumors after 2 weeks, as did transfected and nontransfected B-104 cells. However, the rats injected with transfected C6 cells yielded no tumors after 40 weeks of observation. Two weeks after injection of the transfected C6 cells a small cyst was apparent in six rats. Histologic sections revealed a few glioma cells infiltrated by a large number of mononuclear cells. No infiltration of mononuclear cells was apparent in the glioma tumors resulting from injection of parental (nontransfected) cells, suggesting that the parental cells, but not the antisense IGF-I transfectants, escape the host immune response. PMID- 1594588 TI - Isolation of genes specifically expressed in flat revertant cells derived from activated ras-transformed NIH 3T3 cells by treatment with azatyrosine. AB - We previously reported that mouse NIH 3T3 cells transformed by transfection of activated human c-Ha-ras become apparently normal upon treatment with the antibiotic azatyrosine. The revertant cells maintain their normal phenotype during prolonged culture in the absence of azatyrosine, although activated p21ras is still expressed. The normal phenotype induced by azatyrosine could be due to activation of expression of some cellular gene(s) in the cells that results in suppression of ras function. To identify the genes with increased expression in the revertant cells, we adopted differential screening of recombinants from a phage cDNA library made from mRNA of the revertant cells, hybridized with 32P labeled cDNAs made from mRNAs of the ras-transformed NIH 3T3 cells and the revertant cells. Two clones thus isolated were found to be almost identical to the ras recision gene (rrg), which was identified as a tumor-suppressor gene by Contente et al. [Contente, S., Kenyon, K., Rimoldi, D. & Friedman, R. M. (1990) Science 249, 796-798]. Other genes identified were the collagen type III and rhoB genes. Approximately half the clones were found to contain a sequence corresponding to that of the murine retrovirus-like intracisternal A particle. We speculate that azatyrosine activates several cellular genes in the ras transformed cells and that some of these genes, including rrg, act cooperatively to counteract ras function, resulting in reversion of the ras-transformed cells to the normal phenotype. PMID- 1594589 TI - cDNA cloning and functional activity of a glucocorticoid-regulated inflammatory cyclooxygenase. AB - The antiinflammatory glucocorticoids are potent inhibitors of cyclooxygenase, a key regulator of prostaglandin synthesis; yet, the mechanism(s) by which this occurs is not fully understood. We have cloned a 4.1-kilobase (kb) cDNA, distinct from the previously cloned cyclooxygenase (2.8 kb), that confers cyclooxygenase activity to transfected cells. The mRNA for this newly discovered cyclooxygenase is unique for its long 3' untranslated region containing many AUUUA repeats. Levels of the 4.1-kb cyclooxygenase mRNA are rapidly increased by serum or interleukin 1 beta in mouse fibroblasts and human monocytes, respectively, and decreased by glucocorticoids, whereas levels of the 2.8-kb cyclooxygenase mRNA do not change. Similar effects are seen in the presence of cycloheximide where the 4.1-kb, but not the 2.8-kb, mRNA is greatly superinduced. Thus, there are both constitutive (2.8 kb) and regulated (4.1 kb) cyclooxygenase species, the latter most likely being a major mediator of inflammation. PMID- 1594590 TI - Targeted mutations that ablate either the adenylate cyclase or hemolysin function of the bifunctional cyaA toxin of Bordetella pertussis abolish virulence. AB - Bordetella pertussis, the causative agent of whooping cough, secretes several toxins implicated in this disease. One of these putative virulence factors is the adenylate cyclase (AC) toxin that elevates intracellular cAMP in eukaryotic cells to cytotoxic levels. This toxin is a bifunctional protein comprising both AC and hemolysin (HLY) enzymatic domains. The gene encoding the AC toxin (cyaA) is expressed as part of an operon that includes genes required for secretion or activation of the toxin. Because of this genetic organization, it is difficult to create B. pertussis mutants of cyaA that are ablations of a single enzyme function by conventional means, such as transposon mutagenesis. Therefore, to clarify the role of individual toxin functions in the virulence of B. pertussis, we have used site-directed or deletion mutagenesis and genetic recombination to specifically target the cyaA gene of B. pertussis to produce mutants that lack only the AC or HLY activity of this toxin. A point mutant of B. pertussis with abolished AC catalytic activity was greater than 1000 times less pathogenic to newborn mice than wild-type bacteria, directly demonstrating the importance of the AC toxin in pertussis virulence. Similarly, an in-frame deletion mutant of B. pertussis that lacks HLY is equally avirulent, supporting observations that the HLY domain plays a critical role in AC toxin entry into cells. Furthermore, the genetically inactivated AC toxin produced by the point mutant is antigenically similar to the native toxin, suggesting that this strain may be useful in the development of pertussis component vaccines. PMID- 1594591 TI - Sliding and intermolecular transfer of the lac repressor: kinetic perturbation of a reaction intermediate by a distant DNA sequence. AB - The lac repressor associates with its operator at a rate faster than conventional diffusion allows, either because of one-dimensional diffusion of a captured repressor along the DNA (sliding) or because the tetrameric repressor can be rapidly transferred between DNA sites distant from each other in the primary sequence (direct transfer). We report measurements of relative repressor-operator association rates at physiological operator concentrations. We assay for the ability of DNA targets of equal length (approximately 200 base pairs) containing one or six operator segments to compete for repressor; as the sliding range decreases, the hexameric operator fragment should react up to six times faster than the monomeric operator fragment. We find that the advantage enjoyed by the hexameric fragment varies from little to none at low operator concentration (depending on ionic strength) to more than 3-fold at high concentration. We ascribe this behavior to sliding at low operator concentration and to an increasing contribution of bimolecular direct transfer events as concentration increases. The observations require a "semibound" intermediate state of the protein at operator sites. This species can either undergo a relatively slow (tau greater than 1 sec) unimolecular isomerization to the final complex, or the isomerization can occur in a bridged complex with another operator site, accompanied by transfer to the second operator with probability of 0.5. Bridging alters one or more rate constants in the complex. PMID- 1594592 TI - Rat urate oxidase produced by recombinant baculovirus expression: formation of peroxisome crystalloid core-like structures. AB - Urate oxidase (EC 1.7.3.3), which catalyzes the oxidation of uric acid to allantoin, is present in most mammals but absent in humans and hominoid primates. In rats and most other mammals that catabolize uric acid to allantoin, this enzyme is localized within the crystalloid cores of peroxisomes present in liver parenchymal cells. To determine whether urate oxidase forms these crystalloid cores or whether core-forming protein(s) exist in association with urate oxidase, a baculovirus expression vector system was used to overproduce the full-length rat urate oxidase in Spodoptera frugiperda cells. Urate oxidase was expressed to a level of approximately 30% of the total protein in this system. Immunoblot analysis demonstrated that the baculovirus-generated protein had electrophoretic and immunologic properties similar to those of urate oxidase expressed in rat liver. Immunofluorescence and electron microscopic examination revealed that the overexpressed recombinant urate oxidase is present in both the cytoplasm and the nucleus of infected insect cells as numerous 1- to 3-microns discrete particles. These insoluble protein aggregates, which were positively stained for urate oxidase by protein A-gold immunocytochemical approach, did not appear to be delimited by a single membrane. They revealed a crystalloid structure reminiscent of rat peroxisomal core consisting of bundles of tubules with an inner diameter of approximately 50 A. The recombinant urate oxidase particles, isolated by a single-step procedure, were composed entirely of 35-kDa urate oxidase subunit. These studies indicate that rat urate oxidase is capable of forming insoluble crystalloid core-like structures. PMID- 1594594 TI - Optimal protein-folding codes from spin-glass theory. AB - Protein-folding codes embodied in sequence-dependent energy functions can be optimized using spin-glass theory. Optimal folding codes for associative-memory Hamiltonians based on aligned sequences are deduced. A screening method based on these codes correctly recognizes protein structures in the "twilight zone" of sequence identity in the overwhelming majority of cases. Simulated annealing for the optimally encoded Hamiltonian generally leads to qualitatively correct structures. PMID- 1594593 TI - The highest gene concentrations in the human genome are in telomeric bands of metaphase chromosomes. AB - Chromosome in situ suppression hybridization has been carried out on human metaphase chromosomes to localize the G+C-richest human DNA fraction (which only represents 3.5% of the genome), as isolated by preparative equilibrium centrifugation in Cs2SO4/3,6-bis(acetatomercurimethyl)-1,4-dioxane density gradient. This fraction essentially corresponds to isochore family H3. The rationale for carrying out this experiment is that this isochore family has, by far, the highest gene concentration, the highest concentration in CpG islands, the highest transcriptional and recombinational activity, and a distinct chromatin structure. The in situ hybridization results obtained show that the H3 isochore family is localized in two coincident sets of bands of human metaphase chromosomes: telomeric bands and chromomycin A3-positive 4',6-diamidino-2 phenylindole-negative bands. This result is the first step toward a complete compositional map of the human karyotype. Because the G+C gradient across isochore families is paralleled by a gene concentration gradient, such a map has structural, functional, and evolutionary relevance. PMID- 1594595 TI - Molecular cloning of the breakpoints of a complex Philadelphia chromosome translocation: identification of a repeated region on chromosome 17. AB - Complex translocations in chronic myelogenous leukemia involve various chromosomes, in addition to chromosomes 9 and 22, in a nonrandom fashion. We have analyzed the DNA from leukemia cells characterized by a complex translocation, t(9;22;10;17)(q34;q11;p13;q21), by using the techniques of Southern blot hybridization, in situ hybridization, and molecular cloning; one of the breakpoints is at 17q21, a band that is frequently involved in complex 9;22 translocations. All of the breakpoint junctions and the corresponding normal sequences from the four involved chromosomes have been molecularly cloned. Restriction mapping is consistent with a simple concerted exchange of chromosomal material among the four chromosomes, except that additional changes appeared to have occurred within the chromosome 17 sequences. The cloned sequences on chromosome 17 at band q21 were found to be repeated in normal cells. By fluorescence in situ hybridization, a strong signal is seen at 17q21, but a weaker signal is also present at 17q23. By comparison with other primate species, an inversion in chromosome 17 during evolution appears to be responsible for the splitting of the cluster of repeat units in normal human cells. PMID- 1594596 TI - Proteasomes are regulated by interferon gamma: implications for antigen processing. AB - Class I major histocompatibility complex (MHC) molecules present antigenic peptides of cytoplasmic origin to T cells. As the lengths of these peptides seem restricted to eight or nine amino acids, an unusual proteolytic system must play a role in antigen processing. Proteasomes, a major extralysosomal proteolytic system, are responsible for the degradation of cytoplasmic proteins. We demonstrate that several proteasomal subunits, including MHC-encoded subunits, are regulated by interferon gamma. These data and the finding that MHC-encoded and other interferon gamma-regulated proteasomal subunits are uniquely associated with proteasomes strongly suggest that the immune system has recruited proteasomes for antigen processing. PMID- 1594597 TI - Hemophilia A due to mutations that create new N-glycosylation sites. AB - In studying the molecular defects responsible for cross-reacting material positive hemophilia A, we have identified two patients in whom the nonfunctional factor VIII-like protein has abnormal, slower-moving heavy or light chains on SDS/PAGE. Both patients have severe hemophilia A (less than 1% of normal factor VIII activity) with a normal plasma level of factor VIII antigen. The molecular defects were identified by denaturing gradient gel electrophoresis screening of PCR-amplified products of the factor VIII-coding DNA sequence followed by nucleotide sequencing of the abnormal PCR products. In patient ARC-21, a methionine-to-threonine substitution at position 1772 in the factor VIII light chain creates a potential new N-glycosylation site at asparagine-1770. In patient ARC-22, an isoleucine-to-threonine substitution at position 566 creates a potential new N-glycosylation site at asparagine-564 in the A2 domain of the factor VIII heavy chain. The mobility of these chains on SDS/PAGE was normal after N-Glycanase digestion and procoagulant activity was generated--to a maximum of 23% and 45% of control normal plasma. Abnormal N-glycosylation, blocking factor VIII procoagulant activity, represents a newly recognized mechanism for the pathogenesis of severe hemophilia A. PMID- 1594598 TI - Jasmonic acid/methyl jasmonate accumulate in wounded soybean hypocotyls and modulate wound gene expression. AB - Jasmonic acid (JA) and its methyl ester, methyl jasmonate (MeJA), are plant lipid derivatives that resemble mammalian eicosanoids in structure and biosynthesis. These compounds are proposed to play a role in plant wound and pathogen responses. Here we report the quantitative determination of JA/MeJA in planta by a procedure based on the use of [13C,2H3]MeJA as an internal standard. Wounded soybean (Glycine max [L] Merr. cv. Williams) stems rapidly accumulated MeJA and JA. Addition of MeJA to soybean suspension cultures also increased mRNA levels for three wound-responsive genes (chalcone synthase, vegetative storage protein, and proline-rich cell wall protein) suggesting a role for MeJA/JA in the mediation of several changes in gene expression associated with the plants' response to wounding. PMID- 1594599 TI - The rad3+ gene of Schizosaccharomyces pombe is involved in multiple checkpoint functions and in DNA repair. AB - A number of important molecular checkpoints are believed to control the orderly progression of cell cycle events. We have found that the radiation-sensitive Schizosaccharomyces pombe mutant rad3-136 is deficient in two molecular checkpoint functions. Unlike wild-type cells, the mutant cells are unable to arrest in the G2 phase of the cell cycle after DNA damage by gamma-irradiation and are also incapable of maintaining the dependence of mitosis upon the completion of DNA synthesis. An S. pombe genomic clone that complements the UV sensitivity of the rad3-136 mutant completely restores the missing checkpoint functions. The rad3+ gene is also likely to play a role in DNA repair. PMID- 1594600 TI - A single polypeptide catalyzing the conversion of phytoene to zeta-carotene is transcriptionally regulated during tomato fruit ripening. AB - The cDNA of the gene pds from tomato, encoding the carotenoid biosynthesis enzyme phytoene desaturase, was cloned, and its nucleotide sequence was determined. Cells of Escherichia coli that expressed the tomato pds gene could convert phytoene to zeta-carotene. This result suggests that one polypeptide, the product of the pds gene, can carry out phytoene desaturation in the carotenoid biosynthetic pathway. Transcripts of the pds gene accumulate in orange tomato fruit, indicating transcriptional control of pds expression during fruit ripening. The deduced amino acid sequence of phytoene desaturase indicates that this enzyme in tomato contains 583 amino acids that are highly conserved with respect to the homologous enzymes in cyanobacteria and algae. The deduced amino acid sequences of the phytoene desaturases from other microorganisms (purple bacteria and fungi) appear to be evolutionarily unrelated to those from green photosynthetic organisms. PMID- 1594601 TI - Induction of c-jun protooncogene expression and transcription factor AP-1 activity by the polyoma virus middle-sized tumor antigen. AB - Polyoma virus middle-sized tumor (PymT) antigen is required for neoplastic cell transformation by polyoma virus. We studied changes in gene expression accompanying expression of PymT in murine fibroblasts. These experiments showed that PymT differentially affects several growth-related genes. c-jun protooncogene expression was highly increased, whereas the expression of two growth arrest-specific genes (gas) was reduced, in cells transformed by PymT. Cotransfection experiments showed that the increase in c-jun expression resulted from elevated activity of the transcription factor AP-1 and was mediated through the phorbol 12-tetradecanoate 13-acetate response element in the c-jun promoter. The degree of c-Jun/AP-1 activation by different PymT mutants correlated with their transforming capability, suggesting that regulation of c-Jun/AP-1 activity may play a role in cell transformation by polyoma virus. PMID- 1594603 TI - Biosynthesis of phosphatidylinositol-glycan (PI-G)-anchored membrane proteins in cell-free systems: PI-G is an obligatory cosubstrate for COOH-terminal processing of nascent proteins. AB - It is generally recognized that nascent proteins destined to be processed to a phosphatidylinositol-glycan (PI-G)-anchored membrane form contain a hydrophobic signal peptide at both their NH2 and COOH termini. In previous studies we showed that rough microsomal membranes (RM) prepared from CHO cells can carry out COOH terminal processing. We have now investigated RM prepared from many additional cell types, including frog oocytes, B cells, and T cells, and found that all are competent with respect to COOH-terminal processing. Exceptions were certain mutant T cells that had been shown to be defective at various steps of PI-G anchor biosynthesis [Sugiyama, E., De Gasperi, R., Urakaze, M., Chang, H.-M., Thomas, L. J., Hyman, R., Warren, C. D. & Yeh, E. T. H. (1991) J. Biol. Chem. 266, 12119-12122]. In one such defective mutant, COOH-terminal processing activity of RM could be restored either by transfecting the intact cells with the gene for the deficient step in PI-G synthesis or by adding PI-G extracts to the RM in vitro. Cleavage of the COOH-terminal signal peptide in the RM is therefore dependent on the presence of intact PI-G incorporated into the mature protein. PMID- 1594602 TI - Identification and analysis of the gene encoding human PC2, a prohormone convertase expressed in neuroendocrine tissues. AB - In recent studies we have identified PC2 and PC3, members of a family of serine proteases that are related structurally to subtilisin, and have provided evidence that these are involved in the tissue-specific processing of prohormones and neuropeptides. PC2 is expressed at high levels in the islets of Langerhans, where it participates in the processing of proinsulin to insulin (S.P.S. and D.F.S., unpublished data). To evaluate the regulated expression of the human PC2 (hPC2) gene we have analyzed its structure and characterized its promoter. A map of the gene was constructed by using 11 clones isolated from two human genomic DNA libraries. The gene spans greater than 130 kilobase pairs and consists of 12 exons. Comparison with the structure of the gene encoding human furin, another member of this superfamily, revealed a high degree of conservation of exon-intron junctions. The hPC2 gene was localized to chromosome 20, band p11.2. The 5' flanking region of the hPC2 gene is very G+C-rich and contains six potential Sp1 binding sites but no TATA or CAAT box. Expression of chloramphenicol acetyltransferase reporter fusions containing the putative promoter region was observed to occur in beta TC-3 mouse insulinoma cells but not in HepG2 human hepatoma cells, consistent with the known tissue-specific pattern of expression of the hPC2 gene. Analysis of the level of chloramphenicol acetyltransferase activity with several deletion mutants identified the region from -1100 to -539 from the translation start site as essential for hPC2 promoter activity. PMID- 1594604 TI - Extrachromosomal genetic complementation of surface metalloproteinase (gp63) deficient Leishmania increases their binding to macrophages. AB - A major surface glycoprotein of 63 kDa (gp63) has been previously identified biochemically and genetically as a zinc proteinase conserved in pathogenic Leishmania spp. The functional significance of this proteinase was analyzed by genetic approaches. A 15-kilobase DNA with a tunicamycin-resistance gene from Leishmania amazonensis was ligated in two different orientations into pBluescript containing a gp63 gene from Leishmania major. These plasmid constructs were used to transfect a variant of L. amazonensis deficient in gp63 expression. Both constructs were found to confer tunicamycin resistance with equal efficiency and remained structurally unchanged in the transfectants. RNA and immunoblot analyses showed over-expression of gp63 in the transfectants with one of the two plasmids constructed. The over-produced products were enzymatically active and expressed on the cell surface. Significantly, the transfectants with over-expressed gp63 increased by 2-fold over controls in their binding to macrophages. Evidence presented thus indicates that the gp63 gene constructed in the plasmid as described and introduced exogenously expresses in the gp63-deficient variants and that the expressed products are functionally active. PMID- 1594605 TI - Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency. AB - Corticosterone methyloxidase II (CMO-II) deficiency is an autosomal recessive disorder of aldosterone biosynthesis, characterized by an elevated ratio of 18 hydroxycorticosterone to aldosterone in serum. It is genetically linked to the CYP11B1 and CYP11B2 genes that, respectively, encode two cytochrome P450 isozymes, P450XIB1 and P450XIB2. Whereas P450XIB1 only catalyzes hydroxylation at position 11 beta of 11-deoxycorticosterone and 11-deoxycortisol, P450XIB2 catalyzes the synthesis of aldosterone from deoxycorticosterone, a process that successively requires hydroxylation at positions 11 beta and 18 and oxidation at position 18. To determine the molecular genetic basis of CMO-II deficiency, seven kindreds of Iranian-Jewish origin were studied in which members suffered from CMO II deficiency. No mutations were found in the CYP11B1 genes, but two candidate mutations, R181W and V386A, were found in the CYP11B2 genes. When these mutations were individually introduced into CYP11B2 cDNA and expressed in cultured cells, R181W reduced 18-hydroxylase and abolished 18-oxidase activities but left 11 beta hydroxylase activity intact, whereas V386A caused a small but consistent reduction in the production of 18-hydroxycorticosterone. All individuals affected with CMO-II deficiency were homozygous for both mutations, whereas eight asymptomatic subjects were homozygous for R181W alone and three were homozygous for V386A alone. These findings confirm that P450XIB2 is the major enzyme mediating oxidation at position 18 in the adrenal and suggest that a small amount of residual activity undetectable in in vitro assays is sufficient to synthesize normal amounts of aldosterone. PMID- 1594606 TI - CD43 interferes with T-lymphocyte adhesion. AB - CD43 is a cell-surface sialoglycoprotein of uncertain physiologic function expressed to various degrees by most leukocytes. We tested whether or not CD43 participates in intercellular adhesion by comparing the binding of human T lymphocytes to transfected HeLa cells stably expressing CD43 and sham-transfected HeLa cells (CD43-negative). Significantly fewer T lymphocytes adhered to the CD43 positive HeLa cells than to the CD43-negative HeLa cells. Diminished T-cell adherence to the CD43-positive HeLa cells was seen for all T lymphocytes tested, irrespective of their source or derivation. Antibody-blocking experiments revealed that CD43 interference with T-cell adhesion largely represented interference with T-cell leukocyte function-associated antigen 1 binding to HeLa cell intercellular adhesion molecule 1. The CD43 anti-adhesion effect was not overcome by treating cells with phorbol 12-myristate 13-acetate, a chemical that increases the binding avidity of leukocyte function-associated antigen 1 for intercellular adhesion molecule 1. However, neuraminidase treatment of the HeLa cell transfectants diminished the CD43 antiadhesion effect. These data indicate that CD43 expression by opposing cells can interfere with cell-cell adhesion. The data also suggest that CD43 might regulate T-cell adhesion by interfering with leukocyte function-associated 1 binding to intercellular adhesion molecule 1, a major activation-induced adhesion pathway among lymphocytes. PMID- 1594607 TI - Compartmentation in mammalian cerebellum: Zebrin II and P-path antibodies define three classes of sagittally organized bands of Purkinje cells. AB - The respective roles of genetic and epigenetic factors in generation of pattern formation in the vertebrate nervous system are still poorly elucidated. The mammalian cerebellum is subdivided in parasagittal modules defined by anatomical, physiological, and biochemical criteria. Immunostaining of adult mouse cerebellum with two monoclonal antibodies, P-path, which recognizes 9-O-acetylated glycolipids, and Zebrin II, which recognizes a 36-kDa protein, reveals three classes of sagittally organized bands of Purkinje cells: two complementary groups distinctly immunoreactive to one antibody but not the other and a third group that contains double-labeled cells. No Purkinje cells could be detected that were unreactive to either antibody. The specific and reproducible topography of these three classes of Purkinje cells may be related to the compartmentation of the cerebellum into developmental genetic modules. PMID- 1594608 TI - Yeast flavohemoglobin is an ancient protein related to globins and a reductase family. AB - The hemoglobin of yeast is a two-domain protein with both heme and flavin prosthetic groups. The nucleotide sequences of the cDNA and genomic DNA encoding the protein from Saccharomyces cerevisiae show that introns are absent and that both domains are homologous with a flavoheme protein from Escherichia coli. The heme domains are also homologous with those of O2-binding heme proteins from several other distantly related bacteria, plants, and animals; all appear to be members of the same globin superfamily. Although the homologous hemoglobin of the bacterium Vitreoscilla sp. is a single-domain protein, several bacteria have related O2-binding heme proteins whose second domains have different structures and enzymatic activities: dihydropteridine reductase (E. coli), cytochrome c reductase (Alcaligenes eutrophus), and kinase in the O2 sensor of Rhizobium meliloti. This indicates that one evolutionary pathway of hemoglobin is that of a multipurpose domain attached to a variety of unrelated proteins to form molecules with different functions. The flavin domain of yeast hemoglobin is homologous with members of a flavoprotein family that includes ferredoxin reductase, nitric oxide synthase, and cytochrome P-450 reductase. The correspondence of yeast and E. coli flavohemoglobins indicates that the two-domain protein has been conserved intact for as long as 1.8 billion years, the estimated time of divergence of prokaryotes and eukaryotes provided that cross-species gene transfer has not occurred. PMID- 1594609 TI - Targeted integration of the Ren-1D locus in mouse embryonic stem cells. AB - We have introduced a Ren-1D targeting vector into embryonic stem cells containing the two highly homologous mouse renin genes Ren-1D and Ren-2. Using a polymerase chain reaction (PCR) screen designed to detect targeted integration at Ren-1D and Ren-2, we isolated 15 targeted embryonic stem cell clones, all of which had undergone a gene conversion event at the Ren-1D locus. We did not isolate any clones in which the incoming DNA had recombined with Ren-2. Over the region encompassed by our transgene, Ren-1D and Ren-2 display greater than 95% homology. Our results suggest that the machinery driving gene targeting by means of homologous recombination in mammalian cells is capable of distinguishing between these two sequences. Construction of transgenic mice with the embryonic stem cells reported here carrying a mutated renin gene will permit a greater understanding of the functions of the Ren-1D and Ren-2 gene products and their relative contribution to cardiovascular homeostasis. PMID- 1594610 TI - Regulation of muscarinic acetylcholine receptor mRNA expression by activation of homologous and heterologous receptors. AB - Muscarinic acetylcholine receptors (mAChR) in the embryonic chicken heart undergo agonist-induced internalization and a subsequent decrease in receptor number (downregulation). Cloning studies have identified two subtypes of mAChR expressed in the embryonic chicken heart, the cm2 and cm4 receptors. We report here that persistent activation of the mAChR in cultured chicken heart cells with the cholinergic agonist carbachol causes significant decreases in the levels of both cm2 and cm4 mRNA, as measured by solution hybridization analyses. The half-lives of the cm2 and cm4 mRNAs are not altered by agonist treatment, indicating that agonist most likely regulates mRNA levels by regulating the rate of gene transcription. Activation of mAChR in chicken heart causes both inhibition of adenylate cyclase activity and stimulation of phospholipase C activity. To test whether changes in the levels of intracellular second messengers were involved in the changes in mAChR mRNAs observed following agonist exposure, we determined the effects of incubation with agonists for the A1 adenosine receptors (which inhibit adenylate cyclase in chicken heart) and angiotensin II receptors (which stimulate phospholipase C) on mAChR receptor number and mRNA levels. Activation of these pathways together through heterologous receptors resulted in decreased mAChR number and mRNA levels, although these changes were not as large as those seen with direct activation of the mAChR. These results suggest that regulation of adenylate cyclase and phospholipase C activities may be involved in the regulation of mAChR gene expression. PMID- 1594611 TI - Phytochrome requires the 6-kDa N-terminal domain for full biological activity. AB - Phytochrome is a red/far-red-absorbing photoreceptor that controls many aspects of plant photomorphogenesis. Because proteolytic removal of approximately 6 kDa from the N terminus of 124-kDa oat phytochrome substantially alters many physicochemical properties of the chromoprotein, it has been proposed that the N terminus is required for biological activity. Here we test this hypothesis by comparing tobacco plants expressing full-length oat phytochrome (FL) with plants expressing a 118-kDa oat phytochrome lacking amino acids 7-69 (NA phytochrome). NA phytochrome, like its FL counterpart, exists as a homodimer in solution, is capable of covalently binding chromophore to form a red/far-red-photoreversible product, and is rapidly degraded in vivo after photoconversion to the far-red absorbing form. However, like proteolytically degraded phytochrome missing the N terminus, the absorption maxima of the red- and far-red-light-absorbing forms of NA phytochrome are blue shifted relative to the maxima of the FL chromoprotein, and the rate of dark reversion of the far-red- to red-light-absorbing form is substantially increased. Tobacco plants producing high levels of NA phytochrome do not exhibit the light-exaggerated phenotype characteristic of FL phytochrome overexpression. By comparison of phytochrome-dose-phenotype-response curves generated by using a series of transgenic lines expressing various levels of FL or NA phytochrome, we demonstrate that NA phytochrome has less than 1/5th the biological activity of FL phytochrome expressed in tobacco. Furthermore, the shape of the dose-response curve for plants expressing FL phytochrome indicates that there is a sharp transition between phenotypically normal and abnormal plants over a relatively narrow range of phytochrome content, demonstrating that precise control of phytochrome levels is critical to photomorphogenesis. PMID- 1594612 TI - Cloning of a Rab3 isotype predominantly expressed in adipocytes. AB - We have isolated the cDNA for Rab3D, an additional member of the small molecular weight GTP-binding protein family. Rab3D message is abundant in mouse adipocytes. It is increased during differentiation of 3T3-L1 cells into adipocytes, temporally coincident with the appearance of the insulin-sensitive glucose transporter GLUT4. Rab3D is a close homolog of Rab3A, which is found on the cytoplasmic surface of neurosecretory vesicles and which may be involved in their regulated secretion. Since our previous work showed that in permeabilized adipocytes nonhydrolizable GTP analogs mimic insulin in triggering exocytosis of GLUT4-containing vesicles, Rab3D may be involved in the insulin-induced exocytosis of GLUT4-containing vesicles in adipocytes. PMID- 1594613 TI - Regions of bacteriophage T4 and RB69 RegA translational repressor proteins that determine RNA-binding specificity. AB - RegA protein of T4 and related bacteriophages is a highly conserved RNA-binding protein that represses the translation of many phage mRNAs that encode enzymes involved in DNA metabolism. RB69, a T4-related bacteriophage, has a unique regA gene, which we have cloned, sequenced, and expressed. The predicted amino acid sequence of RB69 RegA is 78% identical to that of T4 RegA. Plasmid-encoded RB69 RegA expressed in vivo represses the translation of T4 early mRNAs, including those of rIIA, rIIB, 44, 45, rpbA, and regA. Nucleotide sequences were determined for several T4 and RB69 regA mutations, and their corresponding repressor properties were characterized. All of the 10 missense mutations affect residues conserved between RB69 and T4 RegA. Two regions of RegA are especially sensitive to mutation: one between Val-15 and Ala-25 and another between Arg-70 and Ser-73. Sequence alignments and mutational data suggest that the region from Val-15 to Ala-25 is similar to helix-turn-helix domains of DNA-binding proteins and confers RNA-binding specificity upon RegA. The RegA691 protein (Ile-24----Thr) has an in vivo phenotype that appears to distinguish site-specific and cooperative binding modes of hierarchical RegA-mediated translational repression. PMID- 1594614 TI - Crossmodal changes in the somatosensory vibrissa/barrel system of visually deprived animals. AB - Cats deprived of vision from birth adapt remarkably well to their situation and show little behavioral impairment. They seem to compensate for their lack of vision by relying more on their auditory and tactile senses. We report here that the facial vibrissae, which are most important for tactile orientation in many animals, show supernormal growth in both cats and mice that have been deprived of vision from birth. Furthermore, the whisker representation in the somatosensory cortical barrel field shows a concomitant enlargement in binocularly enucleated mice: individual barrels are expanded in size by up to one-third. The increased use of the vibrissae in visually deprived animals may stimulate both their own growth and, via activation of the respective neural pathways, the expansion of their central representation. PMID- 1594615 TI - Structural and functional analysis of a replication enhancer: separation of the enhancer activity from origin function by mutational dissection of the replication origin gamma of plasmid R6K. AB - The plasmid R6K possesses three distinct origins of replication: alpha, beta, and gamma. The replication origin gamma of plasmid R6K performs a dual function: (i) as an origin itself and (ii) as an enhancer element required in cis for the activation at a distance of the other two replication origins alpha and beta. We have dissected the gamma origin/enhancer by site-directed mutagenesis and have reached the following conclusions. The origin function can be specifically inactivated without impairing the enhancer function by insertion and/or deletion mutations near the opposite ends of the origin gamma sequence. One such mutation deleted sequences that included the left DnaA site I. The second mutation involved insertion of linker sequences that resulted in a spatial alteration between the right DnaA site II and the VIIth pi binding iteron (tandemly repeated binding sites). Other mutations that either partly or completely deleted the A+T rich sequence adjacent to, but not including, the pi binding iterons also abrogated enhancer and origin function and suggested that pi binding sites were necessary but not sufficient for enhancer activity. Finally, the functional analysis of a set of mutants of the gamma origin/enhancer suggested that a continuous stretch of 300 base pairs is necessary for origin gamma function and that the sequences that included the binding sites for pi, DnaA, and integration host factor proteins are required in the correct stereochemical alignment to impart origin activity. PMID- 1594616 TI - Genetic dissection of pancreatic trypsin inhibitor. AB - In a previous study, a genetic screening procedure was used to identify variants of bovine pancreatic trypsin inhibitor that can fold to an active conformation but that are inactivated much more rapidly than the wild-type protein in the presence of dithiothreitol (DTT). The mechanisms by which 30 of these DTT sensitive variants are inactivated have now been investigated. Some of the amino acid replacements cause rapid inactivation in the presence of DTT because the three disulfides of the native protein are reduced up to 300-fold faster than for the wild-type protein, leading to complete unfolding. Other substitutions, however, do not greatly increase the rate of complete reduction and unfolding but lead to accumulation of an inactive two-disulfide species. There is a striking correlation between the locations of the DTT-sensitive amino acid replacements in the three-dimensional structure of the protein and the mechanisms by which the variants are inactivated. All of the substitutions that cause rapid unfolding are clustered at one end of the folded protein, in the vicinity of the two disulfides that are reduced most slowly during unfolding of the wild-type protein, while substitutions of the other class are all located at the other end of the protein, near the trypsin binding site. These results indicate that the kinetic stability of native bovine pancreatic trypsin inhibitor and its ability to function as a protease inhibitor are largely influenced by residues in two distinguishable regions of the folded protein. PMID- 1594617 TI - Ascorbic acid prevents oxidative stress in glutathione-deficient mice: effects on lung type 2 cell lamellar bodies, lung surfactant, and skeletal muscle. AB - Glutathione deficiency in adult mice leads to lung type 2 cell lamellar body and mitochondrial damage; as reported here, these effects are associated with marked decrease of the levels of phosphatidylcholine (the main component of lung surfactant) in the lung and the bronchoalveolar lining fluid. Severe mitochondrial damage was also found in skeletal muscle. Treatment with ascorbate (1-2 mmol per kg of body weight per day), which led to greatly increased (approximately 2-fold) levels of lung and muscle mitochondrial glutathione, prevented damage to lamellar bodies and mitochondria as well as the decline of phosphatidylcholine levels in lung and alveolar lining fluid. The findings indicate that glutathione deficiency leads to depletion of lung surfactant and that this can be prevented with ascorbate. Administration of ascorbate spares glutathione and prevents cellular damage. Lamellar body degeneration in glutathione deficiency appears to be associated with oxidative damage to the perilamellar membrane, which contains the enzymes required for phosphatidylcholine synthesis. It is notable that although severe glutathione deficiency is lethal to newborn rats, which apparently do not synthesize ascorbate, adult mice are better able to survive such a deficiency because they can synthesize ascorbate. The present studies, which suggest that high doses of ascorbate may be of therapeutic value, emphasize that ascorbate and glutathione have actions in common and that they function together in a physiologically significant antioxidant system. PMID- 1594618 TI - Chimpanzees immunized with recombinant soluble CD4 develop anti-self CD4 antibody responses with anti-human immunodeficiency virus activity. AB - In view of the efficiency with which human immunodeficiency virus replication can be blocked in vitro with anti-CD4 antibodies, the elicitation of an anti-CD4 antibody response through active immunization might represent a useful therapeutic strategy for AIDS. Here we demonstrate that immunization of chimpanzees with recombinant soluble human CD4 elicited an anti-CD4 antibody response. The elicited antibody bound self CD4 on digitonin-treated but not freshly isolated lymphocytes. Nevertheless, this antibody blocked human immunodeficiency virus replication in chimpanzee and human lymphocytes. These observations suggest that immunization with recombinant soluble CD4 from human immunodeficiency virus-infected humans may be feasible and therapeutically beneficial. PMID- 1594619 TI - Monaural interaction of excitation and inhibition in the medial superior olive of the mustached bat: an adaptation for biosonar. AB - In most mammals, the superior olive is the first stage for binaural interaction. Neurons in the medial superior olive (MSO) receive excitatory input from both ears and are sensitive to interaural time or phase differences of low-frequency sounds. The mustached bat (Pteronotus parnellii parnellii), a small echolocating species with high-frequency hearing, probably does not use interaural time or phase differences as cues for sound localization. Although the mustached bat has a large MSO, there is some evidence that it is functionally different from the MSO in nonecholocating mammals. Most MSO neurons in the mustached bat are monaural, excited by a contralateral sound. Their responses are phasic and correlated with either the onset or the offset of a sound. As a first step in determining the origin of these phasic monaural responses, we traced the connections of the MSO by using both retrograde and anterograde transport methods. Excitatory inputs to the MSO originate from spherical cells in the anteroventral cochlear nucleus, almost exclusively from the contralateral side. Glycinergic inhibitory input is relayed from the contralateral cochlear nucleus through the medial nucleus of the trapezoid body. To investigate the interactions of the contralateral excitatory and inhibitory inputs at the level of the MSO cell, we recorded sound-evoked responses and applied glycine or its antagonist by using microiontophoresis. The results show that the phasic response to a contralateral sound is created by interaction of a sustained excitatory input with a sustained inhibitory input, also from the contralateral ear. Whether the response is to the onset or offset of a sound is determined by the relative timing between the excitatory and inhibitory inputs. Thus, in MSO of the mustached bat, the ipsilateral excitatory pathway from the cochlear nucleus seen in animals with low-frequency hearing is virtually absent, and the MSO is adapted for timing analysis by using input from only the contralateral ear. PMID- 1594620 TI - Restoration of motility to an Escherichia coli fliA flagellar mutant by a Bacillus subtilis sigma factor. AB - The activation of additional promoter sites by production of an alternative sigma subunit for RNA polymerase is a common strategy for the coordinate regulation of gene expression. Many alternative sigma factors control genes for specialized, and often narrowly distributed, functions. For example, most of the alternative sigma factors in Bacillus subtilis control genes necessary for endospore formation. In contrast, the B. subtilis sigma D protein controls the expression of genes important for flagellar-based motility and chemotaxis, a form of locomotion very broadly distributed in the eubacteria. A homologous sigma factor, sigma F, controls a similar group of motility genes in the enteric bacteria. The conservation of both promoter specificity and genetic function in these two regulons allowed us to test the ability of a B. subtilis sigma factor to function within an Escherichia coli host. We demonstrate that expression of the B. subtilis sigD gene restores motility to an E. coli strain mutant in the fliA locus encoding the sigma F factor. This result suggests that the B. subtilis sigma D protein can bind to the E. coli core RNA polymerase to direct transcription initiation from at least four of the late operon promoters, thereby leading to the synthesis of flagellin, motor, and hook-associated proteins. Conversely, expression of sigma D protein in a normally chemotactic strain of E. coli (fliA+) leads to a hyperflagellated, nonchemotactic phenotype. PMID- 1594621 TI - Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. AB - A vast amount of data suggests that homologous recombination in mammalian cells is relatively rare as compared to random integration, imposing the need for sophisticated selection protocols to enrich for cells in which homologous recombination has occurred. We here show that one of the key factors in efficient homologous recombination is the use of isogenic DNA to prepare the targeting vectors. Homologous recombination at the retinoblastoma susceptibility gene (Rb) in embryonic stem cells derived from mouse strain 129 was 20-fold more efficient with a 129-derived targeting construct than with a BALB/c-derived construct. The two constructs were identical, except for a number of base sequence divergences between 129 and BALB/c DNA, including base-pair substitutions, small deletions/insertions, and a polymorphic CA repeat. Transfection with an isogenic DNA construct, containing 17 kilobases of homology, yielded a targeting frequency of 78% (of a total of 20,000 drug-resistant colonies), without the use of an enrichment protocol for homologous recombination. This result indicates that, also in mammalian cells, homologous recombination rather than random integration can be the predominant event. PMID- 1594622 TI - Opening of glibenclamide-sensitive K+ channels in follicular cells promotes Xenopus oocyte maturation. AB - The vasorelaxing K+ channel opener P1060 (a pinacidil analog), gonadotropins, and cAMP were shown to activate a glibenclamide-sensitive 86Rb+ efflux from fully grown follicle-enclosed Xenopus oocytes. Glibenclamide-sensitive K+ channels are located in follicular cells. Glibenclamide (i) depressed the gonadotropin- but not the progesterone-induced maturation and (ii) did not significantly modify progesterone production in oocytes exposed to Xenopus gonadotropin. In follicle enclosed oocytes, the opener P1060 very significantly enhanced the oocyte sensitivity to progesterone. This increased sensitivity to the hormone induced by the K+ channel opener was reversed by glibenclamide. Thus these results suggest that the opening of glibenclamide-sensitive K+ channels in follicular cells by gonadotropins (and other activators of this channel) induces a hyperpolarization in the oocyte that greatly facilitates maturation by increasing the oocyte sensitivity to progesterone. PMID- 1594623 TI - A model of the molten globule state from molecular dynamics simulations. AB - It is generally accepted that a protein's primary sequence determines its three dimensional structure. It has proved difficult, however, to obtain detailed structural information about the actual protein folding process and intermediate states. We present the results of molecular dynamics simulations of the unfolding of reduced bovine pancreatic trypsin inhibitor. The resulting partially "denatured" state was compact but expanded relative to the native state (11-25%); the expansion was not caused by an influx of water molecules. The structures were mobile, with overall secondary structure contents comparable to those of the native protein. The protein experienced relatively local unfolding, with the largest changes in the structure occurring in the loop regions. A hydrophobic core was maintained although packing of the side chains was compromised. The properties displayed in the simulation are consistent with unfolding to a molten globule state. Our simulations provide an in-depth view of this state and details of water-protein interactions that cannot yet be obtained experimentally. PMID- 1594624 TI - Cholecystokinin cells purified by fluorescence-activated cell sorting respond to monitor peptide with an increase in intracellular calcium. AB - Cholecystokinin (CCK) is secreted from specific enteroendocrine cells of the upper small intestine upon ingestion of a meal. In addition to nutrients, endogenously produced factors appear to act within the gut lumen to stimulate CCK release. One such factor is a trypsin-sensitive CCK-releasing peptide found in pancreatic juice, known as monitor peptide. This peptide is active within the intestinal lumen and is hypothesized to stimulate CCK secretion by interacting directly with the CCK cell. We have found that monitor peptide releases CCK from isolated rat intestinal mucosal cells and that this effect is dependent upon extracellular calcium. In the present study, we used monitor peptide as a tool for isolating CCK cells from a population of small intestinal mucosal cells. Dispersed rat intestinal mucosal cells were loaded with the calcium-sensitive fluorochrome Indo-1, and CCK secretory cells were identified spectrofluorometrically by their change in fluorescence when stimulated with monitor peptide. Cells demonstrating a change in their emission fluorescence ratio were sorted using a fluorescence-activated cell sorter. More than 90% of the sorted cells stained positively for CCK with immunohistochemical staining. Furthermore, sorted cells secreted CCK when stimulated with membrane-depolarizing concentrations of potassium chloride, dibutyryl cAMP, calcium ionophore, and monitor peptide. These findings indicate that functional intestinal CCK cells can be highly enriched using fluorescence-activated cell sorting. Furthermore, monitor peptide appears to interact directly with CCK cells to signal CCK release through an increase in intracellular calcium. PMID- 1594625 TI - Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome. AB - McCune-Albright syndrome (MAS) is characterized by polyostotic fibrous dysplasia, cafe-au-lait lesions, and a variety of endocrine disorders, including precocious puberty, hyperthyroidism, hypercortisolism, growth hormone excess, and hyperprolactinemia. The diverse metabolic abnormalities seen in MAS share the involvement of cells that respond to extracellular signals through activation of the hormone-sensitive adenylyl cyclase system (EC 4.6.1.1). Mutations that lead to constitutive activation of Gs alpha, the guanine nucleotide-binding regulatory protein that stimulates adenylyl cyclase activity, have been identified in a subset of human growth hormone-secreting pituitary tumors and human thyroid tumors. We report here the identification of a mutation in the gene encoding Gs alpha in a patient with MAS. Denaturing gradient gel electrophoresis was used to analyze amplified DNA fragments including exon 8 or exon 9 of the Gs alpha gene. In one subject with MAS a G-to-A transition was found in exon 8 of one of the two alleles encoding Gs alpha. This single-base substitution results in the replacement of arginine by histidine at position 201 of the mature Gs alpha protein. Semiquantitative analysis of amplified DNA indicated that the mutant allele was less prevalent than the wild-type allele in peripheral leukocytes and was present in very low levels in skin. These findings support the previous contention that the segmental distribution and variable expression of the cutaneous, skeletal, and endocrine manifestations of MAS reflect an underlying somatic mosaicism. Further, these results suggest that the molecular basis of MAS is a postzygotic mutation in Gs alpha that causes constitutive activation of adenylyl cyclase. PMID- 1594626 TI - Transduction of a foreign histocompatibility gene into the arterial wall induces vasculitis. AB - Autoimmune vasculitis represents a disease characterized by focal inflammation within arteries at multiple sites in the vasculature. Therapeutic interventions in this disease are empirical and often unsuccessful, and the mechanisms of immune injury are not well-defined. The direct transfer of recombinant genes and their expression in the arterial wall provides an opportunity to explore the pathogenesis and treatment of vascular disease. In this report, an animal model for vasculitis has been developed. Inflammation has been elicited by direct gene transfer of a foreign class I major histocompatibility complex gene, HLA-B7, to specific sites in porcine arteries. Transfer and expression of this recombinant gene was confirmed by a polymerase chain reaction and immunohistochemistry, and cytolytic T cells specific for HLA-B7 were detected. These findings demonstrate that expression of a recombinant gene in the vessel wall can induce a focal immune response and suggest that vessel damage induced by cell-mediated immune injury can initiate vasculitis. PMID- 1594627 TI - Human immunodeficiency virus type 1 infection of neural xenografts. AB - Human immunodeficiency virus type 1 (HIV-1) infection is highly specific for its human host. To study HIV-1 infection of the human nervous system, we have established a small animal model in which second-trimester (11 to 17.5 weeks) human fetal brain or neural retina is transplanted to the anterior chamber of the eye of immunosuppressed adult rats. The human xenografts vascularized, formed a blood-brain barrier, and differentiated, forming neurons and glia. The xenografts were infected with cell-free HIV-1 or with HIV-1-infected human monocytes. Analysis by polymerase chain reaction revealed HIV-1 sequences in DNA from xenograft tissue exposed to HIV-1 virions, and in situ hybridization demonstrated HIV-1 mRNA localized in macrophages and multinucleated giant cells. Pathological damage was observed only in neural xenografts containing HIV-1-infected human monocytes, supporting the hypothesis that these cells mediate neurotoxicity. This small animal model allows the study of direct and indirect effects of HIV-1 infection on developing human fetal neural tissues, and it should prove useful in evaluating antiviral therapies, which must ultimately target HIV-1 infection of the brain. PMID- 1594628 TI - Transforming growth factor beta induces myoblast differentiation in the presence of mitogens. AB - Transforming growth factor beta 1 (TGF-beta 1) added to L6E9 rat skeletal myoblasts in mitogen-rich medium induces a rapid decrease in c-myc expression and delays progression through the G1 phase of the cell cycle. This growth inhibitory response is followed by cell commitment to terminal differentiation with elevated expression of myogenin muscle determination genes, induction of muscle-specific proteins, and formation of multinucleated myotubes. These results suggest that TGF-beta 1 may act as a physiological inducer of myogenic differentiation in mitogen-rich environments, and its otherwise reversible growth inhibitory effect may become permanent if coupled to induction of terminal differentiation. PMID- 1594629 TI - IgE-secreting cells in the thymus: correlation with induction of tolerance to IgE. AB - We have shown previously that normal mice become tolerant to endogenous IgE when they are approximately 2 weeks old and that this corresponds closely with the initial appearance of IgE in serum. Tolerance evidently is restricted to T cells, since B cells responsive to IgE are present in neonatal and adult mice. The present report shows that IgE-secreting cells can be detected in the thymus between days 7 and 11 after birth and that the onset of tolerance to IgE occurs at the age of 11 days. Similar results were obtained in A/J and (BALB/c x A/J)F1 mice. This suggests that tolerance is induced in the thymus, probably by cells bearing peptide fragments of IgE. The order of appearance of IgE-secreting cells is thymus, spleen, and mesenteric lymph nodes. PMID- 1594630 TI - Legionella pneumophila mip gene potentiates intracellular infection of protozoa and human macrophages. AB - Legionella pneumophila is an intracellular parasite of freshwater protozoa and human macrophages. Recent studies determined that the macrophage infectivity potentiator (Mip) surface protein, a prokaryotic homolog of the FK506-binding proteins, is required for optimal infection of macrophages. To determine whether Mip is also involved in L. pneumophila infection of protozoa, we examined the ability of a strain lacking Mip to parasitize Hartmannella amoebae and Tetrahymena ciliates. After 3 days of incubation, approximately 1000-fold fewer bacteria were recovered from protozoan cocultures infected with the Mip- strain than from those cocultures infected with an isogenic Mip+ strain. The mip mutant was, however, not impaired in its ability to bind to amoebae cell surfaces, indicating that Mip is involved in bacterial resistance to intracellular killing and/or intracellular multiplication. These data suggest that L. pneumophila employs similar genes and mechanisms to infect human cells and protozoa. Furthermore, they support the hypothesis that the ability of L. pneumophila to parasitize macrophages and hence to cause human disease is a consequence of its prior adaptation to intracellular growth within protozoa. PMID- 1594632 TI - An LH-RH antagonist inhibits the behavioral effects of the agonist D-TRP-6-LH-RH in mice. AB - The effects of a potent LH-RH receptor antagonist, [Ac-4-Cl-D-Phe1,2,D-Trp3,D Arg6,D-Ala10]LH-RH (ORG 30276), on the behavioral actions of the LH-RH agonist, D Trp-6-LH-RH, were studied in mice. The subcutaneous (SC) administration of 100 micrograms/kg D-Trp-6-LH-RH inhibited ambulation in an open-field, produced analgesia in the hot-plate and tail-flick tests. These effects of the agonist were totally antagonized by pretreatment with ORG 30276 at a dose of 100 micrograms/kg SC. In the apomorphine-induced cage-climbing test, both the agonist and the antagonist alone or together suppressed the duration of stereotyped behavior in dose-dependent manner, but, as there was no additive synergism after combined treatments, it seems that the two substances mutually diminish each other's effects. The results indicate that the behavioral effects of the LH-RH agonist can be antagonized by pretreatments with a potent LH-RH antagonist designed to block pituitary LH-RH receptors, with the exception of the suppression of apomorphine-induced cage-climbing, where special type of receptors and/or mechanisms might be involved. PMID- 1594633 TI - Acamprosate modulates synaptosomal GABA transmission in chronically alcoholised rats. AB - Male Sprague-Dawley rats were pulmonary alcoholised for 30 days. Six were treated with acamprosate (400 mg/kg/day, PO) during alcoholisation. The control nonalcoholised group also received acamprosate (400 mg/kg/day, PO) during the 30 days. At the end of the experiment, brains areas (cortex, hippocampus, thalamus, striatum, and olfactory bulbs) were dissected for the study of synaptosomal 3H GABA uptake. In another experiment, GABA levels were determined in the same areas using HPLC with electrochemical detection. Blood ethanol levels were also measured during alcoholisation. Acamprosate treatment did not modify blood ethanol levels. In cortex and olfactory bulbs, alcoholisation increased 3H-GABA uptake (Vmax) with an increase in the affinity (Km). 3H-GABA uptake was not affected by alcoholisation in other brain areas. In hippocampus and thalamus, acamprosate treatment enhanced 3H-GABA uptake (Vmax) only in alcoholised rats. Moreover, in thalamus, alcoholisation enhanced GABA levels. The effect of alcohol and acamprosate on GABA presynaptic events is discussed and it is concluded that the action of ethanol and acamprosate on GABA transport could be, in part, responsible for the modulation by acamprosate treatment of ethanol behaviour. PMID- 1594631 TI - pp125FAK a structurally distinctive protein-tyrosine kinase associated with focal adhesions. AB - Expression of the Rous sarcoma virus-encoded oncoprotein, pp60v-src, subverts the normal regulation of cell growth, which results in oncogenic transformation. This process requires the intrinsic protein-tyrosine kinase activity of pp60v-src and is associated with an increase in tyrosine phosphorylation of a number of cellular proteins, candidate substrates for pp60v-src. We report here the isolation of a cDNA encoding a protein, pp125, that is a major phosphotyrosine containing protein in untransformed chicken embryo cells and exhibits an increase in phosphotyrosine in pp60v-src-transformed chicken embryo cells. This cDNA encodes a cytoplasmic protein-tyrosine kinase which, based upon its predicted amino acid sequence and structure, is the prototype for an additional family of protein-tyrosine kinases. Immunofluorescence localization experiments show that pp125 is localized to focal adhesions; hence, we suggest the name focal adhesion kinase. PMID- 1594634 TI - Behavioral concomitants of regional changes in the brain's biogenic amines after apomorphine and amphetamine. AB - Behavioral and neurochemical changes were analyzed in rats after systemical injections of the dopamine receptor agonist apomorphine (0.5 mg/kg) or the indirect agonist amphetamine (1.0 mg/kg). As expected, amphetamine led to an increase in locomotion, whereas apomorphine resulted in decreases in locomotion, rearings, and grooming. The analysis of biogenic amines in tissue samples showed that amphetamine decreased 3,4-dihydroxy-phenylacetic acid (DOPAC) levels and DOPAC/dopamine ratios in the neostriatum, and resulted in a lower 5-hydroxyindole 3-acetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the ventral mesencephalon. Apomorphine decreased the dopamine metabolites [DOPAC, homovanillic acid (HVA), 3-methoxy-tyramine (3-MT)] and their respective metabolite/transmitter ratios and increased dopamine levels in the neostriatum. Similar decreases in dopamine metabolites or their ratios were found in the ventral mesencephalon, septum, and frontoparietal cortex but not the thalamus. In addition to its effects on dopamine, apomorphine decreased norepinephrine in the ventral neostriatum and 5-HT and 5-HIAA in the cortex. Correlations between behavioral activity and neurochemical metabolism (using the metabolite transmitter ratios for the latter) revealed relationships between locomotion and serotonergic activity in the thalamus of animals treated with amphetamine. Evidence for a relationship between locomotion or rearings and dopaminergic activity was found in all six brain areas analyzed. Here, the pattern of correlation was dependent on the kind of treatment and the behavioral and neurochemical measures. These results support earlier findings on the neurochemical effects of apomorphine and amphetamine in the neostriatum and ventral mesencephalon, and add new evidence for an action on the septal area, thalamus, and frontoparietal cortex. PMID- 1594635 TI - Effects of duration and timing of environmental enrichment on voluntary ethanol intake in rats. AB - The effects of exposure to five environmental rearing conditions on subsequent voluntary ethanol intake was examined. Male weanling rats were reared for 60 days in either an enriched environment, individually, or in a smaller enriched environment (quasienriched). The quasienriched environment was employed to allow for a group measurement of ethanol intake. Following the initial 60-day environmental exposure period, the three initial groups (Enriched, Isolation, Quasienriched) were randomly subdivided into five groups (Enriched/Isolation, Isolation, Isolation/Quasienriched, Quasienriched, Quasienriched/Isolation) and exposed to increasing concentrations of ethanol (3-9% v/v) in a free choice with water. Results indicated that exposure to an enriched environment for 60 days does not alter ethanol intake. In contrast, rats exposed to the quasienriched environment while having access to ethanol demonstrated a significant increase in voluntary ethanol intake as compared to all other groups. Exposure to different environmental conditions while having access to ethanol was not by itself sufficient to alter ethanol intake. These data are discussed in terms of the amount and timing of exposure to an enriched environment necessary to alter voluntary ethanol intake. PMID- 1594636 TI - Raised [3H]-5-HT release and 45Ca2+ uptake in diazepam withdrawal: inhibition by baclofen. AB - The effect of diazepam withdrawal (2 mg/kg/day) on release of [3H]-5 hydroxytryptamine(5-HT) and [14C]-GABA from rat cortical and hippocampal slices was studied. No changes in [14C]-GABA release (basal, K(+)-evoked, uptake) from slices of either region were observed. Similarly, all parameters of [3H]-5-HT release were unchanged in cortical slices. However, during diazepam withdrawal, depolarised [3H]-5-HT release from hippocampal slices was raised with no changes in basal release or uptake into the slices being found. This increase could be prevented by in vivo administration of 1 mg/kg baclofen--this dose having no significant effect on [3H]-5-HT release from hippocampal slices of control rats. To further investigate this effect, 45Ca2+ uptake into hippocampal synaptosomes was examined and found to be increased during withdrawal. This was blocked by in vitro addition of 10 microM (-)baclofen, which had no effect on 45Ca2+ uptake in controls. Inhibition of 45Ca2+ uptake by (-)baclofen was also enhanced in nonwithdrawn diazepam-treated rats, but not in rats treated acutely with diazepam. The results from both studies indicate that chronic diazepam treatment increases neuronal sensitivity to baclofen. These results are discussed with reference to the anxiogenic state during diazepam withdrawal and a recent report of reversal of this behaviour by baclofen. PMID- 1594637 TI - Puffing behavior during the smoking of a single cigarette in a naturalistic environment. AB - The 36 participants in this study were habitual low-yield cigarette smokers, medium-yield cigarette smokers, and switchers from medium- to low-yield cigarettes. All participants smoked both low- (0.4 mg) and medium-nicotine (0.9 mg) cigarettes during the study. Puffing indices were recorded during the first two cigarettes, after an overnight abstinence of smoking, by a portable flowmeter processor unit in a naturalistic environment. The puff volumes per cigarette and per day were significantly lower while switching to higher-yield cigarettes, mainly due to a decrease in the number of puffs and longer interpuff intervals, but also due to a decline in puff duration and flow rate. However, the downregulation by puff volume was incomplete, at most two thirds, as calculated by machine smoking yields. Within the course of smoking a single cigarette, the flow rate was quite stable, puff duration and puff volume decreased toward the end of the cigarette, and interpuff interval was longest during the middle of the cigarette. Total puff volumes per cigarette were similar in the first two cigarettes of the day after an overnight abstinence of smoking, with no significant differences in other puff parameters. Diurnal cotinine excretion revealed that nicotine titration in switching situations was very accurate among switchers and medium-yield cigarette smokers, but not among the low-yield cigarette smokers, and so called oversmoking was found with the higher-nicotine brand. Preferred cigarette type had little effect on the puffing patterns of smokers in single cigarettes. PMID- 1594638 TI - Minaprine cancels scopolamine effects on the rat's acquisition of passive avoidance responses in two multitrial paradigms. AB - The antiamnesic activity of minaprine has been studied in male Wistar rats. Two multitrial paradigms were employed: the light-dark box test (aversive stimulus: 0.6-mA foot-shocks) and the tail-handling test (aversive stimulus: manual tail handling). In both paradigms, intraperitoneal scopolamine administration 30 min before testing significantly impaired the acquisition of the passive avoidance conditioned response. There were no significant differences in either paradigm between control rats and those to whom scopolamine and minaprine were simultaneously administered. These results show that minaprine fully protects the acquisition process of conditioned responses against scopolamine impairment not only in one-trial tests but also in multitrial paradigms. The effects of minaprine in reversing memory deficits are discussed in relation to its stimulating activity on central cholinergic systems. PMID- 1594639 TI - Fluctuations in responses to diazepam during the oestrous cycle in the mouse. AB - Administration of diazepam (0.28 mg/kg, IP; 60 min) to male mice or to female mice at oestrus or dioestrus increased the number of transitions made between the light and dark chambers of a test apparatus, a presumed anxiolytic action. However, the same dose of diazepam had no effect on light/dark transitions at late dioestrus, proestrus, or metoestrus II. At metoestrus I, this test dose of diazepam induced a decrease in the number of light/dark transitions and significant changes in other test parameters indicative of an increase in fearfulness or light aversion. Concentrations of diazepam in the brain after intraperitoneal injection were not influenced by the stage of the oestrous cycle, suggesting that the observed changes in responses to diazepam reflect changes in sensitivity to this drug rather than alterations in distribution or metabolism. The results indicate a physiological influence of ovarian steroid hormones on sensitivity to the benzodiazepine tranquilisers. PMID- 1594641 TI - Role of monoamines in the male differentiation of the brain induced by androgen aromatization. AB - Cerebral androgen aromatization has been described as a mechanism responsible for masculinization of the brain, and monoamines seem to be involved in sexual differentiation of the brain. The aim of this study was to investigate the possible implication of monoamines in the masculinization of the brain induced by cerebral androgen aromatization not only in the classic hypothalamic areas but also in some extrahypothalamic ones. For this purpose, 1-day-old male Wistar rats were injected intraventricularly with 5 mg/kg of a suspension of an aromatase inhibitor, LY43578. Saline was administered to male and female control groups. At adulthood, open-field, heterotypical, and homotypical sexual behavior tests were performed and cerebral amines were determined by HPLC-ED. Behavioral tests revealed feminine-like exploratory activity and defecation rate in the treated group, as well as an 89% lordotic response and decreased number of mounts plus intromissions. Testosterone levels were not affected by the treatment. Striatal and limbic serotonergic metabolism showed a sexual dimorphism, higher in males than females, that disappeared in the treated group. From these results, we suggest a possible role of extrahypothalamic serotonin in the mediation of the estrogen-induced mechanisms of behavioral sexual differentiation. PMID- 1594640 TI - Wild running elicited by microinjections of bicuculline or morphine into the inferior colliculus of rats: lack of effect of periaqueductal gray lesions. AB - Bicuculline methiodide, a GABAA receptor antagonist, or a high dose of morphine was injected at the same site within the inferior colliculus (IC) of rats. Both drugs elicited the same behavioral activity (wild running). However, the time course and magnitude of the effects of the two drugs differed. Since the behavioral activation elicited was reminiscent of what was found with microinjections of bicuculline methiodide or morphine into the periaqueductal gray (PAG), we lesioned the PAG in another group of rats. It was found that extensive lesions of the PAG including those extending to the medial part of the superior colliculus did not significantly reduce the wild running. PMID- 1594642 TI - Role of catecholamines in the courtship behavior of male ring doves. AB - The role of catecholamines in the expression of male courtship behavior in ring doves was examined using central administration of pharmacological agents. Males treated with 6-hydroxydopamine or U-14,624, which depleted norepinephrine (NE) levels in the preoptic-hypothalamic area, showed increased levels of bow-coo and nest-coo displays. Conversely, males treated with tyramine or desipramine, which elevated NE levels in the preoptic-hypothalamic area, showed decreased levels of bow-coo and nest-coo displays. Drug-induced changes in dopamine levels were not consistent with any changes in behavior. This suggests that in the male ring dove NE in the preoptic-hypothalamic area is important in the expression of courtship displays. PMID- 1594643 TI - Phase-out filter perforation: effects on human tobacco smoke exposure. AB - Phase-Out is a mechanical device that dilutes the cigarette smoke stream by mechanically perforating cigarette filters. Machine testing of Phase-Out-treated cigarettes suggested that smoke exposure reductions of 90-95% could be achieved with the device. This study evaluated exposure to carbon monoxide (CO) and nicotine when humans (N = 10) smoked Phase-Out-treated cigarettes under controlled laboratory conditions. Using boost (i.e., change from baseline) measures of constituent exposure, reductions ranging from 30-80% were seen for both nicotine and carbon monoxide. Orderly graded reductions in constituent exposure were observed for both nicotine and carbon monoxide as the number of filter perforations increased from zero to six holes, with no further reduction at the eight-hole condition. Percentage reductions in constituent exposure generally corresponded well to those anticipated from machine testing, indicating that the controlled smoking technology was valid and that the Phase-Out device operated as expected in a human smoking assay. The utility of partial constituent level reductions is discussed both with regard to lowered health risks of smoking and ease of quitting when partial reduction is used as a gradual weaning preparation for quit attempts. PMID- 1594644 TI - Effects of nicotine on the threshold for rewarding brain stimulation in rats. AB - The rewarding effects of nicotine alone and nicotine challenged with mecamylamine, a nicotine receptor blocker, or naloxone were determined using a rate-independent discrete-trial threshold measure of brain-stimulation reward in rats. If nicotine acts as other drugs of abuse, it would be expected to lower the reward threshold, that is, increase an animal's sensitivity to rewarding brain stimulation, and naloxone would be expected to block this effect, as it does other stimulants in this paradigm. Nicotine was found to significantly lower the reward threshold and mecamylamine blocked this effect. However, although naloxone increased the variability of nicotine's effect on the reward threshold, it failed to dose dependently block nicotine's threshold-lowering effect. PMID- 1594645 TI - Endurance training changes central and peripheral responses to physostigmine. AB - Whether the pharmacodynamics of physostigmine (Phy) [rate of decarbamylation of cholinesterase (ChE) enzyme] (Kd) is altered due to acute and/or trained exercise in brain and various tissues of rat has been addressed. Acute exercise (AE) + Phy increased, whereas endurance training (ET) + Phy decreased ChE activity in brain, red blood cells (RBC), and various tissues as compared to Phy alone. The Kd of brain ChE was significantly increased (181% of control) by AE + Phy and decreased (66% of control) by ET + Phy as compared to Phy alone. There was a slight increase (114% of control) in Kd of RBC-ChE in AE + Phy as compared to Phy alone. The Kd of heart ChE was significantly decreased (44% of control) by ET + Phy as compared to Phy alone. The Kd of diaphragm ChE was significantly increased (384% of control) in AE + Phy and decreased (80% of control) in ET + Phy as compared to Phy alone. The Kd of muscle ChE significantly decreased (67% of control) by AE + Phy as compared to Phy alone, but ET + Phy did not affect the Kd in muscle. These results suggested that AE and ET have opposite effects on Kd after Phy administration. PMID- 1594646 TI - Effects of an antitussive mixture and its constituents in rats discriminating methamphetamine from saline. AB - The discriminative effects of over-the-counter antitussive syrup containing dihydrocodeine (DHC), methylephedrine (MEP), caffeine (CAF), and chlorpheniramine (CPA) were compared with those of methamphetamine (MA) in a drug discrimination experiment using rats. Rats were trained to discriminate the effects of MA at 0.5 mg/kg SC and saline for food reinforcement under the fixed-ratio 10 schedule in a two-lever operant chamber situation. In substitution testing using a cumulative dose procedure by the subcutaneous route, DHC (4 and 8 mg/kg, expressed hereafter as referred to cumulative dose) or CPA (16-64 mg/kg) individually did not produce MA lever selection. On the other hand, MEP (128 mg/kg) and CAF (64 mg/kg) produced MA lever selection 41.5 and 57.2% of the time, respectively. The complete mixture (16 mg/kg DHC + 32 mg/kg MEP + 33.2 mg/kg CAF + 6.4 mg/kg CPA) produced MA level selection 65.8% of the time. The partial mixture containing only MEP + CAF at the above doses produced MA lever selection 95.6% of the time. Thus, the complete mixture only partially substituted for MA in rats while the partial mixture containing MEP and CAF completely substituted for MA. PMID- 1594647 TI - Evaluation of the discriminative stimulus and reinforcing effects of sertraline in rhesus monkeys. AB - Rhesus monkeys (N = 4) were allowed to self-administer cocaine (0.03 mg/kg/injection) under a fixed-ratio 10 (FR 10) schedule during daily 2-h experimental sessions. When responding was stable, a variety of doses of sertraline, a serotonin reuptake blocker under development as an antidepressant, were made available for self-administration. Baseline conditions were reinstated between doses of sertraline. Cocaine 0.03 mg/kg/injection maintained high rates of injection, while total saline injections decreased to low levels within four to seven sessions. Sertraline (0.05-0.4 mg/kg/injection) did not maintain self administration above saline levels in three of the four monkeys. In the fourth, responding was marginally above saline levels at two doses but was not systematically related to dose. In a second experiment, rhesus monkeys (N = 6) were trained to discriminate either d-amphetamine (0.56-1.0 mg/kg, IG) or pentobarbital (10 mg/kg, IG) from saline in a discrete-trials shock avoidance/escape paradigm. Sertraline (4.0-32 mg/kg) failed to substitute for either d-amphetamine or pentobarbital as a discriminative stimulus. These results suggest that sertraline is unlikely to have abuse potential in humans and is unlikely to have either d-amphetamine-like or pentobarbital-like subjective effects. PMID- 1594648 TI - Hormone responses to sedative drugs and cold exposure in two rat lines with high and low alcohol sensitivity. AB - Two rat lines bred for differences in motor impairment in the tilting plane test after a moderate dose of ethanol were compared for peripheral hormone responses. The alcohol-sensitive ANT rats had significantly lower plasma corticosterone concentrations than the alcohol-insensitive AT rats 30 min after an IP saline injection. Ethanol (2 g/kg, IP) and lorazepam (3 mg/kg, IP) injections increased the corticosterone concentration in ANT rats. Sodium barbital (160 mg/kg, IP) did not produce any increase in these rats; instead, it prevented any increase caused by a tilting plane test procedure 10 min before decapitation. Three trials on the tilting plane significantly elevated the corticosterone concentration in saline treated ANT rats, but produced no additional increase in drug-treated ANT rats. In AT rats, drug injections caused no significant corticosterone increase but the tilting plane test procedure after barbital (lorazepam) treatment(s) elevated the corticosterone concentration. Cold exposure (+4 degrees C for 30 min) of the drug naive animals elevated their concentrations of serum and adrenal corticosterone, thyrotropin, and growth hormone, but not of prolactin and luteinizing hormone. The increase in serum corticosterone was greater in AT than ANT rats, whereas the increase in serum thyrotropin was slightly greater in ANT rats. No differences between the rat lines were found in the growth hormone, prolactin, and luteinizing hormone levels. The results confirm and extend our earlier findings of the inability of ANT rats to produce additional stress responses to behavioral challenges when being intoxicated by sedative drugs, which may at least partly account for their increased sensitivity to sedative drugs. PMID- 1594649 TI - Reduction of frequency of seizures by carbamazepine during cobalt experimental epilepsy in the rat. AB - Adult female Sprague-Dawley rats rendered epileptic by bilateral cerebral implantation of cobalt wire were simultaneously prepared with permanent cortical and temporalis muscle electrodes for continuous recording of electroencephalogram and electromyogram activities. Carbamazepine (50 or 100 mg/kg) was administered intraperitoneally twice daily days 8-12 after cobalt implantation. The high dose of carbamazepine was effective in decreasing seizure incidence each day of its administration, but the lower dose was effective in decreasing seizure incidence only for 6 h following its administration on days 8 and 9. These results provide additional evidence that cobalt epilepsy in the rat is a valid model for the study of seizure disorders. PMID- 1594650 TI - Operant place conditioning measures examined using two nondrug reinforcers. AB - Detection of water and social play reinforcers by a place conditioning method based on instrumental conditioning was investigated in rats and compared to detection by conditioned place preference, a method currently used primarily to measure drug reinforcement. Operant place conditioning measures of reinforcement were choices between the reward and nonreward chambers during an apparatus exploration test and during a discrete-trials choice test and also, in some experiments, choices and latencies of chamber entry during training. Three of these four measures showed larger reinforcement effects than did the conditioned place preference measure of relative time spent in the reward chamber. By all reinforcement measures, conditioned place preference training was effective with water reinforcement but was ineffective with social reinforcement. Operant place conditioning was effective with both reinforcers by all measures. PMID- 1594651 TI - Operant place conditioning measures examined using morphine reinforcement. AB - A new place conditioning procedure for assessing drug reinforcement, based on drug administration following chamber entry, was examined in rats and compared to conditioned place preference (which is based on chamber exposure of drugged animals). Besides relative time subsequently spent in the morphine chamber, choices between the drug and nondrug chambers were recorded during the time test and during a discrete-trials choice test. In some experiments, either choices or latencies of chamber entry were recorded during training. Most choice and latency measures showed larger reinforcement effects than did time spent. Placement training was somewhat less effective than operant place conditioning overall, but produced significant time differences and discrete-trial choices in four of five groups. With intravenous morphine, the lengthy chamber exposures generally used in conditioned place preference were unnecessary. PMID- 1594652 TI - Cocaine and amphetamine facilitate retention of jump-up responding in rats. AB - The effects of cocaine and d-amphetamine administration on the acquisition of an automated jump-up active avoidance task were examined in two separate experiments. On days 1 and 2, male Sprague-Dawley rats received one escape-only training trial, followed immediately by the intraperitoneal injection of cocaine, amphetamine, or saline. On day 3, subjects received eight escape/avoidance trials. The posttraining administration of cocaine (2.75 and 5.55 mg/kg) and amphetamine (0.3 and 1.0 mg/kg) on days 1 and 2 facilitated jump-up avoidance performance on day 3. Importantly, both cocaine and amphetamine enhanced learning and memory under experimental conditions that allowed for drug-free training and testing. PMID- 1594653 TI - Zacopride, a 5-HT3 receptor antagonist, reduces voluntary ethanol consumption in rats. AB - The effect of the selective 5-HT3 receptor antagonist, zacopride, was assessed in male Sprague-Dawley rats in free choice (6% ethanol and water) experiments. In Experiment 1, single zacopride (0.01-10 mg/kg, IP) injections failed to alter ethanol (ET) consumption during 1-h restricted ET access. In Experiment 2, zacopride (5.0 and 10 mg/kg, IP) injected twice daily for 5 days significantly reduced ET intake and ET preference during 24-h free access to 6% ET and water without altering the total volume of fluid consumed. Thus, the schedule of ET access (i.e., free vs. restricted) and/or the duration of drug treatment may determine the efficacy of pharmacological agents in altering ET preference. 5-HT3 receptor blockade may reduce serotonin/dopamine-mediated maintenance of ET preference; a process that may proceed via extinction mechanisms. PMID- 1594654 TI - Cocaine enhances one-way avoidance responding in mice. AB - We reported previously that posttraining cocaine injections enhance subsequent performance of an automated jump-up avoidance response and a trough avoidance response in rats. In the present study we examined the species generality of the cocaine enhancement by investigating the effects of posttraining cocaine injection on subsequent performance of a one-way active avoidance response in mice. Cocaine (30 mg/kg, IP) administered to mice immediately following completion of two escape-only trials on day 1 significantly enhanced avoidance response performance on day 2. Neither lidocaine nor cocaine methiodide, when administered in doses equimolar to the effective cocaine dose, altered performance on day 2. These data indicate that cocaine's enhancement of avoidance responding in mice probably is neither peripherally mediated nor attributable to its local anesthetic properties. PMID- 1594655 TI - Effect of scopolamine on the electrical resistance of the paw pads of mice. AB - We examined the electrical resistance of the paw pads of mice under the same conditions as used previously in studies of the passive avoidance response. Administration of scopolamine (0.05-1 mg/kg, SC) 10 or 30 min prior to placement of animals in an experimental box resulted in a profound increase in electrical resistance. In contrast, subcutaneous injection of butylscopolamine (1-20 mg/kg), diazepam (1 or 2 mg/kg), or pentobarbital (10 or 20 mg/kg) did not substantially alter subject resistance. Scopolamine may act on the CNS to induce increased paw skin resistance. PMID- 1594656 TI - 17th Symposium of AGNP. Nuremberg, October 2-5, 1991. Abstracts. PMID- 1594657 TI - Thermoregulatory responses of rats exposed to 9.3-GHz microwaves: a comparison of E and H orientation. AB - The purpose of this study was to determine the effects of exposure orientation relative to electric and magnetic fields (E and H fields) on the thermal, cardiovascular, and respiratory changes in ketamine-anesthetized rats exposed to far-field, continuous-wave, 9.3-GHz radiofrequency radiation (RFR). Irradiation (specific absorption rate = 12.5 W/kg in both orientations; power levels of 79 and 59 mW/cm2 in E and H orientations, respectively) was conducted to produce 1 degree C colonic temperature changes (38.5 to 39.5 degrees C). During experimentation, arterial blood pressure and respiratory rate, colonic (Tc) tympanic (Tt) left and right subcutaneous (Tsl & Tsr) (sides toward and away from RFR source), and tail temperatures (Tta) were continuously recorded. The Tsr change during E-orientation exposure was considerably less than the Tc change; the Tt and Tsr (H-orientation) changes approximated the Tc increase; and the Tsl and Tta changes (both orientations) were considerably greater than the Tc increase. The Tt and Tsl increases were virtually equal under the two exposure conditions; however, the Tsr increase was significantly greater during H orientation irradiation, and the Tta increase was significantly greater during E orientation exposure. Heart rate and mean arterial pressure increased significantly during irradiation; however the cardiovascular responses were not affected by exposure orientation. The latter findings at 9.3 GHz contrast with the marked cardiovascular response differences between E- and H-orientation exposure noted during previous studies at 0.7 to 2.45 GHz. PMID- 1594659 TI - Contraction due to bimetallic, short-lived super-coiling in the helical, double stranded filaments of striated muscle. AB - The possibility of a super-coiling of the thin filament is studied. The bimetallic super-coiling might contribute to the power-stroke. The calculation of the axial shortening of the proposed super-coiling leads to a very surprising geometric fitting: the maximal axial shortening of the super-coiling, without any loop, of the thin filament segment (38.5 nm) is equal to the axial repeat of cross-bridges (14 nm). According to the present model, the sarcomere shortening is caused by the axial shortening of the super-coiled actin filament. The top view of the super-coiled segment shows a dual half-circle form. There are experimental evidences for such a type of formation in electron micrographs. According to this model, the widely accepted sterically hidrance model on association of actin and myosin can be neglected. One of the main roles of calcium is to make the thin filament segment flexible enough for the association. PMID- 1594658 TI - Membrane lipids of Mycoplasma orale: lipid composition and synthesis of phospholipids. AB - Lipid composition of Mycoplasma orale was examined and compared with that of horse serum added to the growth medium. Ratios of cholesterol/cholesterol ester and sphingomyelin/phosphatidylcholine were much higher in M. orale than in the horse serum, indicating the organism incorporates selectively cholesterol and sphingomyelin. A distinct difference between the lipids from the two sources was that in phospholipids of M. orale almost all (greater than 95%) of the fatty acyl residues were saturated whereas nearly half of the residues were unsaturated in horse serum phospholipids. Approximately one third of M. orale phospholipids was phosphatidylglycerol, which was synthesized by the organism as was demonstrated by 32P-labeling experiment. Its acyl residues consisted mainly of C16:0 and were efficiently labeled with 14C-palmitate but not with 14C-acetate. These results clearly indicate the de novo synthesis of phosphatidylglycerol by M. orale is through acylation with exogenous saturated fatty acids. On the other hand, all the phosphatidylcholine and sphingomyelin of M. orale were derived from the medium. The 14C-labeling experiment demonstrates that no fatty acid synthesis takes place nor exogenous fatty acid can be incorporated so efficiently as phosphatidylglycerol, suggesting that extremely high proportion of saturated fatty acyl residues in these phospholipids is the consequence of saturation directed to the acyl chains of the incorporated phospholipids. PMID- 1594660 TI - Aging mechanism associated with a function of biowater. AB - Magnetic resonance imaging (MRI) pictures of the forearms of four human subjects belonging respectively to each of four generations of the same family were taken, and aging-associated changes in the humerus, epithelium, fat tissue, muscle and blood observed. It was found that together with morphological changes the proton density and the spin-lattice relaxation time (T1) of biowater in each tissue underwent chronological aging-induced changes. An aging mechanism associated with the function of biowater is deduced from the present result and from related experimental findings previously reported. PMID- 1594661 TI - Reverse micelles of dipalmitoyl phosphatidyl choline in chloroform and their interactions with dapsone. AB - 1H NMR studies of DiPalmitoyl Phosphatidyl Choline (DPPC) in CDCl3 at various concentrations indicate that DPPC exists as reverse micelles for concentrations beyond 6 mM. The chemical environments of the two acyl chains of DPPC are inequivalent and the inequivalence decreases with increasing DPPC concentration. At low concentrations of DPPC (less than 1.0 mM) intramolecular interactions predominate, whereas at high concentrations, intermolecular interactions predominate. Addition of water to this system, at high concentrations of the phospholipid, reduces the intermolecular interactions. In the presence of the antileprotic drug, Diamino Diphenyl Sulfone (DDS or Dapsone), significant shifts were observed only in the choline resonances of DPPC and the amino resonance of the drug, showing that the amino group of DDS interacts with the head group of DPPC. PMID- 1594662 TI - A note: paramagnetic ions influence on water proton spin lattice relaxation times. PMID- 1594663 TI - Influence of denervation on smooth muscle response to repeated administration of cyclophosphamide, cytosine arabinoside, or their combination. AB - Cyclophosphamide, 40 mg.kg-1, cytosine arabinoside, 2 mg.kg-1 or their combination, were all given once weekly to chicks for 5 weeks. The expansor secundariorum muscle of the left wing of each chick was then surgically denervated leaving that of the right wing to serve as the control. Drug administrations continued for a further 5 weeks before the responses of normal and denervated expansor muscles were determined pharmacologically. Cyclophosphamide depressed the response of the expansor muscle to noradrenergic nerve stimulation but enhanced the response to noradrenaline and potassium chloride. Cytosine arabinoside enhanced responses of expansor muscles to noradrenergic nerve stimulation and noradrenaline, but depressed responses evoked by potassium chloride. The combination enhanced responses to nerve stimulation, noradrenaline, and potassium chloride. Expansor muscles were unresponsive to acetylcholine and anticancer drugs failed to restore the responsiveness to acetylcholine except the combination. Denervation depressed responses to noradrenergic nerve stimulation but caused supersensitivity to noradrenaline; this was more marked in the combination and cyclophosphamide groups, with no change in sensitivity seen in the cytosine arabinoside group. The denervated expansor muscle responded to acetylcholine in the order, combination much greater than cyclophosphamide greater than control greater than cytosine group. Denervated expansor muscles from anticancer groups were supersensitive to potassium chloride, with the combination group having the most pronounced effect. It is suggested that denervation influences smooth muscle sensitivity to agonist drugs which can modify the effects of anticancer drugs on smooth muscle. PMID- 1594664 TI - Place conditioning reveals the rewarding aspect of social interaction in juvenile rats. AB - Rewards, as diverse as food, sweetened solutions, copulation, electrical brain stimulation, and drugs abused by humans, have been shown to condition place preferences in rats. Juvenile rats will readily learn to traverse a T-maze for the opportunity to interact with another similar-aged rat. This suggests that play behavior is rewarding. Experiment 1 examined whether play (as quantified by rough-and-tumble pinning) would act as a sufficient reward to condition a place preference (CPP). Experiment 2 examined whether pairings with a nonplaying partner would decrease the time spent in the preferred side and thus suggest a conditioned place aversion (CPA). In Experiment 1, dominant juvenile rats were given free access to a CPP apparatus and a side preference for one of the two physically distinct sides was determined. Dominant rats were then conditioned twice daily over four days in the CPP apparatus. They spent their first session confined in their preferred side with a scopolamine-treated partner (that rendered the partner unable to respond to play solicitations) and during the second session, dominant rats were confined to their less preferred side with a submissive play partner. The number of dorsal contacts, as well as frequency and duration of pinning, were recorded. Following conditioning, side preference was redetermined. A similar procedure was used in Experiment 2 except that the subjects underwent conditioning on their less-preferred side without a play partner. Results of Experiment 1 demonstrated that the dominant rats significantly increased (198.6%) the time spent on the originally less-preferred side after play conditioning.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594665 TI - Copulatory behavior and reflexive penile erection in rats after section of the pudendal and genitofemoral nerves. AB - Two experiments probed the roles of the pudendal and genitofemoral nerves in sexual behavior. Male rats were tested for copulatory behavior and reflexive erections after transection of the sensory (SP) or motor (MP) branches of the pudendal nerves and, in Experiment 2, section of the genitofemoral (GF) nerve alone or in combination with the SP nerves. Damage to the GF nerve had no apparent effects. Division of the SP nerve severely impaired the ability of males to achieve intromission, and hence ejaculation, and reflexive erections were drastically reduced. However, this treatment caused impairments less complete than those previously described for more distal deafferentation by section of the dorsal penile nerves or by application of topical anesthetics to the glans penis. Penile autotomy following SP section was delayed but not avoided by daily treatment with amitriptyline. Transection of the MP nerves had the most drastic effects, preventing reflexive erections, although some intromissions (but no ejaculations) occurred during copulation. Although urinary function was also disrupted by MP transection, the impairment in sexual function is tentatively ascribed to chronic hyperinvolution of the penile corpora following loss of phasic vasoconstrictive stimulation normally supplied via the MP nerves. The pattern of results suggests that the pudendal nerves make different contributions to penile erection in different contexts. PMID- 1594666 TI - A chronic stress state in rats: effects of repeated stress on basal corticosterone and behavior. AB - The chronic stress state has previously been defined as persistent visceral arousal coupled with behavioral abnormalities. To determine the number of stressor exposures necessary to induce a chronic stress state, male rats were given 2 hours of inescapable shock on 10, 7, 4, or 3 consecutive days. The 3-day stress group had the most pervasive changes in the variables measured: persistently elevated basal plasma corticosterone (CORT), continued weight loss in the post-stressor period, and abnormal behavior. More exposures to the stress regimen did not produce higher CORT levels or greater behavioral changes. Acutely stressed rats, exposed to 1 day of inescapable shock, had persistent CORT elevations without the other changes seen in the 3-day stress group. The data suggest that 3 days of our stress regimen are sufficient to produce a state of chronic stress and that some signs of this state begin to appear as early as the first exposure to our inescapable stress regimen. PMID- 1594667 TI - Protein selection by rats adapted to high or moderately low levels of dietary protein. AB - After preliminary studies on flavor acceptability, patterns and indices of subsequent feeding behavior were monitored by computer in young rats which were adapted to 15% or 70% casein diets before being offered, sequentially, choices between flavored diet pairs in which the proportions of percentage casein were 5/65, 5/55, 5/45, 5/35 and 5/25. Similarly adapted rats received these choices in the reverse sequence. Rats adapted to 15% casein usually ate randomly from the diet pairs and selected approximately 15-30% casein; individual behaviors were prominent. The 70% casein groups avoided the higher casein diet, often within minutes (except for the first-offered 5/25 choice), and seldom selected more than 10% casein; individual differences were infrequent. Such rats also distinguished between flavored 70% and 65% casein diets. Sizes and numbers of meals and rates of eating differed for the paired diets, especially for rats adapted to 70% casein. A flavor added to the 70% casein adaptation diet was not avoided when present only in the 5% casein diet of a 5/65 choice. Rats adapted to 70% soy protein before receiving flavored 5/65 to 5/25 choices selected 20-28% soy protein, a level far above those of casein selections by rats adapted to 70% casein. Dietary adaptation and type of protein thus affect subsequent diet selection and feeding patterns and indices. PMID- 1594668 TI - Stimulation by voluntary exercise of adrenal glucocorticoid secretion in mature female hamsters. AB - The possibility that habitual voluntary running induces a chronic change in adrenal glucocorticoid synthesis and secretion was examined in freely running mature female hamsters, in whom this behavior accelerates growth, reduces body fat levels, and elevates core temperature. Hamsters were free to run on horizontal discs or in vertical wheels between 32 and 80 days, in 14L:10D or in 10L:14D photoperiods, and at the end of this period, corticosterone and cortisol steroidogenesis and serial plasma corticosterone concentrations during day and night were used as measures of the chronic stimulation of adrenal cortical activity. Habitual voluntary running significantly increased steroidogenesis of both glucocorticoids and plasma corticosterone concentrations and alone accounted for all the variance in enhanced synthesis and secretion of corticosterone. Acute exercise and/or the nocturnal phase of circadian period enhanced the chronic stimulatory effects of exercise on cortisol. Despite its voluntary and apparently stress-free nature, running induces chronic increases in basal glucocorticoid secretion in mature female hamsters. Putative oversecretion of corticotropin releasing factor in freely running hamsters could account for increased steroidogenesis, acceleration of growth, reduced body fat levels, and core temperature elevation. PMID- 1594669 TI - Iron, transferrin, and haptoglobin levels after a single bout of exercise in men. AB - Twelve, healthy male university student volunteers, between the ages of 20 and 23, were studied. All subjects were considered normal after cardiopulmonary and electrocardiographic examination. The maximal aerobic capacity (Vo2 max) of each subject was determined. The exercise programmes were performed on a mechanically braked Monark cycle ergometer. The subjects were required to perform the three tests, one per week. Each subject had a catheter inserted in an antecubital vein and blood samples were drawn at rest and at the end of exercise. Before and immediately after each exercise session total proteins (TP), hematocrit (Hct), hemoglobin (Hb), and other hematological parameters were measured. Serum iron (Fe), transferrin (TRF), and haptoglobin (HPT) were also determined. Immediately after the end of the exercise (TPT, RST, and IET), TP, Hb, Hct, and RBC increased significantly. TRF and HPT concentrations remained unchanged and iron decreased significantly after maximum sustained test (RST). PMID- 1594670 TI - Plasma glucose levels and leverpress avoidance versus escape behaviors in rats. AB - The relationship between performance in an avoidance conditioning paradigm and the plasma glucose levels of Sprague-Dawley rats was examined in two experiments. In Experiment 1 we investigated whether glucose levels varied with the animal's relative success at acquiring the avoidance task. Results indicated that animals classified as avoiders (60% avoidance and above) had lower glucose levels than animals classified as escapers (30% avoidance and below). In Experiment 2 we looked at whether glucose levels showed within-subject changes with avoidance acquisition. Results demonstrated that glucose levels showed reductions if an animal learned the avoidance response. Subjects that did not learn the response showed no such reduction. Such results suggest that the physiological response to stress is attenuated by acquisition of successful coping behaviors that exercise control over the onset of aversive events. PMID- 1594671 TI - Seasonal productivity of lizard femoral glands: relationship to social dominance and androgen levels. AB - Social and hormonal correlates of femoral gland productivity were investigated in groups of adult and juvenile green iguanas (Iguana iguana) over 12 months. Femoral gland productivity, pore size, and the percentage of lipids in the secretions were correlated with plasma testosterone (T) levels in dominant, although not in subordinate, adult males. Secretory activity peaked during the breeding months, at which time dominants produced more secretion than subordinates. Pore size in juvenile males was positively correlated with plasma T levels and frequency of headbob displays in the months corresponding to the adult breeding season. After 18 months of age, individuals that performed visual displays had significantly larger pores than individuals that did not display. These results indicate that femoral gland secretions could function in the ontogeny and maintenance of dominance relationships. PMID- 1594672 TI - Delayed matching-to-sample performance by rats in a new avoidance-motivated maze: response to scopolamine and fimbria-fornix lesions. AB - A new avoidance-motivated detour-maze in which memory for an immediately preceding sample event could be assessed was evaluated by testing seven 6-month old male F-344 rats with a delayed matching-to-sample (DMTS) paradigm. Rats first received extensive pretraining with this paradigm over several months and after a minimum of 1,390 choice-trials demonstrated great proficiency in this maze. Studies were then conducted to establish cholinergic and hippocampal involvement in the DMTS task by using drug manipulations (scopolamine and physostigmine), and after lesions to the fimbria-fornix (FF) pathway. A high dose (1.0 mg/kg) of scopolamine but not a low dose (0.3 mg/kg) significantly interfered with choice accuracy as measured by errors and trials to criterion; physostigmine (0.01 and 0.03 mg/kg) had no significant effect; and fimbria lesions significantly disrupted both choice accuracy and runtime performance. Disruption was most pronounced on difficult problems (different paths to the goal). After lesions only, considerable within-trial perseverative errors occurred during the early postlesion weeks on four difficult problems from among the 18 tested. Results were discussed in terms of (a) specificity of this disruption, (b) indications of proactive interference effects, and (c) the movement-related excitation component of maze learning. The present results accord with earlier findings of disruption by scopolamine and FF lesions in a 14-unit T-maze, both mazes having similar performance requirements of shock avoidance and multiple 90-degree turns along the paths to the goal. The present results affirm that this new detour maze provides a viable approach for assessing cognitive performance in a within subject design and thereby offers new possibilities for testing various aspects of cognitive processing, particularly for aged rodent models, in a complex aversive situation. PMID- 1594673 TI - Approach, avoidance, and contact behavior of individually recognized animals automatically quantified with an imaging technique. AB - A low-cost system was developed that allows the assessment of the location and the direction of movements of two individually recognized animals in a social interaction. The program was validated by (i) assessing deliberately induced approach and avoidance movements of artificial objects, (ii) the effects of known differences in social behavior between differently treated rats, and (iii) repeatedly testing social behavior under similar circumstances to assess enhanced social contact due to being familiar with the arena. Movements toward and away from each other of individually housed versus group-housed animals, and of young versus aged animals, were analyzed by the system. The results obtained, demonstrated that in the case of randomly moving artificial objects specific approachers or avoiders could not be identified, whereas isolated and young rats showed more approach behavior than their respective controls. In addition, the algorithm applied for calculating relative approach and avoidance movements elucidated differences between groups that were not noticed by human observers. Social contact behavior of rats was assessed automatically. Habituation to the testing situation in repeated testing increased social contact behavior. PMID- 1594674 TI - Behavioral heterogeneity in Sprague-Dawley rats. AB - Because of consistent individual differences in animal behavior, it is often difficult to interpret experimental data. We therefore attempted to rank Sprague Dawley rats by a hierarchical ascendant clustering technique using data from avoidance conditioning and open-field testing (scores of exploratory activity before, during, and after an unpredictable noise stress, and calculated stress related inhibition). This procedure allowed partition of the animal population into distinctive groups and subgroups, extremes being represented by low avoidance-low emotional and high avoidance-high emotional animals. These results are in discrepancy with others showing an opposite pattern of emotional responses in rat lines selectively bred for low or high avoidance. Considering the psychophysiological variability of the animal population in experimental designs may thus be more informative than classical statistical methods, particularly in the evaluation of drug effects or environmental adaptation. PMID- 1594675 TI - Copulatory analgesia in male rats ensues from arousal, motor activity, and genital stimulation: blockage by manipulation and restraint. AB - The effect of copulation on the vocalization threshold to tail shock (VTTS) was assessed in freely-moving, sexually experienced, Wistar male rats. Mean VTTS during the first copulation was 40% above the baseline values and slightly decreased during the first postejaculatory interval (PEI; 28% above baseline). VTTS mean values further increased during the second copulatory series (93% above baseline and 63% during the PEI). Testing at the same intervals in noncopulating rats did not induce analgesia. VTTS values also increased after the display of either one ejaculation (E), five intromissions (I), or five mounts (M), the analgesia persisting for at least 20 min. Analgesia following M was smaller and shorter than that observed after either I or E. Analgesia developed gradually during copulation since VTTS values after five I were significantly higher than those after one I. The incidence of vocalizations to suprathreshold shocks (STS, 20% above the VTTS) occurring during various phases of copulation was also studied to determine the onset and short-term fluctuations of copulatory analgesia. The proportion of STS inducing vocalizations decreased from 91% (mean of individual proportions) before copulation, to 24% during copulation, and to 25% during the PEI. A maximal reduction in the proportion of vocalizations to STS was found during the last third of copulation. Nearly all vocalizations to STS during copulation occurred when subjects were quiescent, while few or no vocalizations occurred when rats were engaged in sexual activity, i.e., during M, I, or penile grooming. In contrast to the above-mentioned data, no significant analgesia was observed using the tail-flick latency test (TFL) following either E, five I, or five M.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594676 TI - Variations in scent marking and ultrasonic vocalizations by Long-Evans rats across the estrous cycle. AB - The purpose of the present study was to investigate whether the signaling behaviors of female Long-Evans rats varies over the estrous cycle. Scent marking and 50-kHz ultrasonic mating vocalizations, in response to a devocalized sexually experienced male, changed in frequency across the cycle, both behaviors being highest at proestrus/early estrus. Vocalizations were recorded on every day of the cycle and also in females showing no regular cycles. In contrast, scent marking was rarely observed during the estrous cycle except at proestrus/early estrus. These results suggest that both behaviors, which increase around the time of sexual receptivity, may help to coordinate reproduction and further suggest an endocrine basis for the changes observed over the estrous cycle. PMID- 1594677 TI - Inescapable footshocks induce progressive and long-lasting behavioural changes in male rats. AB - Long-term behavioural consequences of exposure to a brief (15 min) session of inescapable footshocks (10 x 6 s, 1 mA) were investigated in male rats. The time course of the effects of inescapable footshocks was assessed by studying the behaviour of groups of rats at different post-stress intervals. Footshocked rats (S) did not differ from control (C) rats (exposed to the shock box for 15 min) in their behavioural response to an open field whether tested 1 h or 4 h post stress. However, one day after shocks, S rats showed less locomotion and rearing, and more immobility and attention as compared to C rats. At 7 days or 14 days post-stress, S rats exhibited decreased locomotion, rearing, sniffing, and grooming, and increased immobility, attention, and defecation relative to C rats. In a second experiment, we investigated whether footshocks affect the behavioural response to a sudden drop in background noise during exposure to a novel environment. At 21 days post-stress, S rats showed a markedly enhanced immobility response to this stimulus as compared to C rats. In order to investigate whether rats could be exposed repeatedly to the open field without affecting the differences in behaviour between the two treatment groups, C and S rats were tested in an open field for the first time at 7 days post-stress, which yielded the typical effects of footshocks. When these rats were exposed to a second open field test one week later, the behavioural responses of C and S rats were not different.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594678 TI - Subtotal lesions of the amygdala: the rostral central nucleus in passive avoidance and ulceration. AB - Rats received small bilateral electrolytic or ibotenate lesions of the rostral part of the amygdaloid central (rACE) or lateral (rAL) nuclei, or caudal part of the basolateral nuclei (cBL), or electrolytic lesions of the dorsal hippocampus (HIPP). All groups were tested in a drinking passive avoidance (PA) task that appears less sensitive to deficits in acquisition/retention or activity/spatial perception than are many other PA tasks, and more specifically sensitive to deficits in generation of fear. Consistent with this interpretation, performance in the task was facilitated, not deficient, in the HIPP group. Electrolytic lesions of rAL produced a mild deficit in PA, but ibotenate lesions did not, and neither did the more caudal lesions of the cBL groups. Ibotenate lesions of rACE did produce a deficit in PA, consistent with views of a role of this part of the amygdala in fear. Electrolytic lesions of rACE produced a very profound PA deficit and also blocked the rapid development of gastric erosions by water restraint stress, effects that were not found with ibotenate lesions in this location. This suggests a particular contribution of fibers passing through rACE to some of the more marked effects of electrolytic lesions of rostrodorsal portions of the amygdala. PMID- 1594679 TI - Analysis of the relationships between self-stimulation sniffing and brain stimulation sniffing. AB - Determination of current thresholds for self-stimulation and electrically elicited sniffing from electrodes placed into lateral hypothalamic and ventral tegmental areas of rats revealed a tight correlative relationship between the two phenomena (r values of approx 0.9 at both sites). Thresholds for sniffing were never higher than those for self-stimulation, while approximately half the animals had higher self-stimulation than sniffing thresholds, suggesting that electrically elicited sniffing may better index the underlying psychobiological process that mediates self-stimulation. That both phenomena reflect the same basic process was suggested by the fact that 48 h of food deprivation consistently reduced the thresholds for both self-stimulation and sniffing, while 24 h of food deprivation had only marginal effects on both. The implications for understanding the nature of self-stimulation processes is discussed. PMID- 1594680 TI - Conditioned neuroendocrine and cardiovascular stress responsiveness accompanying behavioral passivity and activity in aged and in young rats. AB - Mean arterial pressure (MAP), heart rate (HR), plasma epinephrine (E), plasma norepinephrine (NE), and plasma corticosterone (CORT) were measured in 3-month- and 24-month-old male Wistar rats exposed to a conditioned emotional stress response (CER) paradigm and a conditioned defensive burying (CDB) paradigm. In the CER situation blood samples were taken during reexposure to the training environment one day after a single inescapable footshock (0.6 mA, AC for 3 s) had been administered. In the CER paradigm the young rats displayed passive behavior (immobility) accompanied by an increase in plasma levels of CORT and E, whereas both the control and conditioned animals showed increased NE responses. Previously shocked aged rats exhibited an attenuated plasma NE response, whereas levels of E remained elevated to a greater extent. Aged animals showed elevated basal levels of CORT one day after footshock administration. Stress-induced immobility was preserved in the aged rats. These animals had an increase in basal MAP values and a decrease in basal HR values compared to young ones. In the CDB paradigm, rats were exposed to a nonelectrified probe 1 day after the repeated shock (2 mA/contact) procedure. Young rats displayed defensive burying accompanied by increments in MAP, HR, CORT, and NE. The aged animals showed similar hormonal, autonomic, and behavioral stress responses. Thus, the age related alterations in neuroendocrine and autonomic response patterns are apparent in stressed animals during behavioral passivity in absence of control (CER) rather than during active control (defensive burying). PMID- 1594681 TI - Feeding conditions and estrous cycle of female rats under the activity-stress procedure from aspects of anorexia nervosa. AB - The present study investigated the application of female rats with activity stress as an animal model for anorexia nervosa. Young female rats were singly housed in activity-wheel cages with food-restricted schedule (2, 3, or 4 h of food availability per day) for 3 weeks. Estrous cycle, body weight, food intake, and wheel revolution were recorded daily. Gastric pathology was also observed using the endoscopic technique. Rats that were subjected to either a 3- or 4-h feeding schedule exhibited the cessation of estrous cycle, loss of body weight, and suppression of food intake. These animals also showed a remarkable increase in running activity. However, they had no gastric lesions throughout the experimental period. On the contrary, the 2-h feeding schedule elicited severe gastric lesions and high mortality. The results suggest that behavioral and physiological changes of the young female rats with 3 or 4 h feeding share some symptoms of anorexia nervosa, although their anorexia is not self starvation. PMID- 1594682 TI - Fetal heart rate response to milk predicts expression of the stretch response. AB - On the day before birth, rat fetuses respond to an intraoral infusion of milk with a stretch response that resembles the behavior of suckling pups at the nipple. Unlike the postnatal response, which occurs coincident with milk ejection, the fetal stretch occurs 3-5 min after milk infusion. Measurement of fetal heart rate (HR) is useful as a predictor of the fetal stretch response. Expression of the stretch response was preceded by a reduction in HR variability and a transient episode of bradycardia. Fetuses that did not stretch showed a delayed reduction in HR variability and no evidence of HR deceleration. Systematic changes in fetal HR may be indicative of changes in fetal state associated with milk infusion and the stretch response. PMID- 1594683 TI - Vasopressin deficiency abolishes a sexually dimorphic behavior in Brattleboro rats. AB - The role of vasopressin (VP) in a sexually dimorphic behavior, the extinction of a conditioned taste aversion, was investigated in male and female rats of three different genotypes. This behavior was examined with a two bottle test in the wild-type Long-Evans (LE) rats, and then in partially VP deficient heterozygous (HET-BB) and completely VP deficient homozygous (HO-BB) Brattleboro rats. In Experiment 1, non-deprived male and female LE rats were given aversions to a sucrose solution by pairing it with a LiCl injection. The rate of extinction of the aversion upon reexposure to ad lib sucrose solution was examined and observed to be sexually dimorphic. Female LE rats extinguished at a significantly more rapid rate than males. Experiment 2 compared HET-BB and HO-BB male and female rats using the same paradigm. Neither of these VP-deficient groups showed sexual dimorphism of the extinction behavior. The data suggest that intact VP levels are necessary to observe the expression of this sexually dimorphic behavior. PMID- 1594684 TI - Amygdala kindling increased fear-response, but did not impair spatial memory in rats. AB - The behavioral effects of amygdala kindling, a model of experimental epilepsy in rats, are reported. The animals were stimulated twice a day until stage 5 (generalized clonic) seizures were obtained three times. Two weeks later the performance of the amygdala-kindled and sham-operated rats was tested in the open field test, on the elevated plus maze, elevated bridges, and in the Morris water maze. The results show that amygdala kindling decreased exploratory and other motor activity in the open-field test, had anxiogenic effects on the elevated plus-maze, decreased boldness on the elevated bridges, but had a negligible affect in the spatial memory task. These results suggest that amygdala kindling affects the normal fear reaction of rats, a response that is known to be mediated through the amygdaloid pathways. PMID- 1594685 TI - Modulation of daily water intake by dopamine in caudate and accumbens nuclei in rats. AB - Bilateral lesions of accumbens and caudate nuclei resulted in significant and sustained increase in water intake. Administration of different doses of dopamine (DA) into these nuclei facilitated a dose-dependent increase in 24-h water intake, whereas injection of spiperone following administration of DA inhibited DA-facilitated water intake in a dose-dependent manner. Conversely, administration of DA and spiperone did not elicit any change in water intake in septal nuclei; rather septal lesion facilitated the water intake. This suggests that the nucleus accumbens and nucleus caudatus act as facilitatory thirst areas and that DA is a possible dipsogenic neurotransmitter in these nuclei. This also suggests that the nucleus septal lateralis is a thirst-inhibiting centre where DA may not be involved in dipsogenesis. PMID- 1594686 TI - The intrauterine position phenomenon and precopulatory behaviors of house mice. AB - The effects of intrauterine position on two sexually dimorphic, precopulatory, reproductive behaviors, were investigated in male and female mice of three different genetic strains. The two behaviors were: (i) urinary odor preference and (ii) ultrasonic mating vocalizations. In addition, anogenital distance was measured both at birth and later in adulthood as a morphological index of masculinization. The intrauterine positions of individual mice relative to male and female siblings were classified according to two different classification schemes based upon hypotheses of interfetal steroid transfer: (i) the contiguity hypothesis which is based on diffusion of steroids within the uterus and (ii) the transvasculature hypothesis which posits the movement of fetal steroids via the maternal vasculature. In contrast to expectations, intrauterine position defined by either the contiguity hypothesis or the transvasculature hypothesis, did not have a consistent effect on urinary odor preferences, ultrasonic mating vocalizations, or anogenital distance in male and female house mice. PMID- 1594687 TI - The effects of bilateral and unilateral vibrissotomy on behavior within aquatic and terrestrial environments. AB - Introducing an untreated rat to a novel environment typically results in thigmotaxis or wall-seeking behavior and the unilateral removal of the vibrissae induces an asymmetry in thigmotaxis. The present study investigated the effects of bilateral and unilateral removal of the vibrissae (vibrissotomy) upon the rat exhibiting thigmotaxis within aquatic and terrestrial environments. Unilateral vibrissotomy resulted in directional thigmotaxis asymmetry toward the intact vibrissae side within both environments. Within the aquatic environment, the unilateral vibrissotomy group swam a significantly longer distance than the other two groups. The data are discussed in terms of activation and sensory information. PMID- 1594688 TI - Cold increases and warmth diminishes stress-induced rise of colonic temperature in rats. AB - It is generally believed that the rise of core temperature of rats induced by handling is due to a shift of set-point temperature as in fever. Changes in core temperature due to set-point shifts should not be affected by changes in the ambient temperature. Nevertheless, when the colonic temperature of rats was taken in a cold environment the usual emotional rise was higher and when the colonic temperature was taken in a warm environment the emotional rise was lower. These results contradict the hypothesis that the emotionally induced rise in temperature of rats is a fever. PMID- 1594689 TI - Daily rhythmicity of the rat acoustic startle response. AB - We have measured the acoustic startle response (ASR) amplitude and latency in rats housed in a 12:12 light:dark (LD) cycle. The response amplitudes to eliciting stimuli (ES) of 110 dB or 120 dB (white noise) were significantly higher (nearly two-fold) during D than during L. Similar, but nonsignificant, trends were also observed at ES intensities of 90 dB or 100 dB. While some significant LD ASR latency differences were observed, we cannot ascribe them to the photoperiodic phase at this time. These findings conclusively demonstrate that the mammalian ASR amplitude exhibits daily rhythmicity. PMID- 1594691 TI - Pathogenesis, natural history, and classification of HIV infection. AB - Much has been learned about the pathogenesis and natural history of AIDS over the past decade. The causative agent is now known to be a human retrovirus that selectively infects CD4 lymphocytes and monocyte/macrophages. The structure, genetic composition, and major proteins of HIV have been identified, and its basic pathophysiology defined. Antibody tests have been developed to screen for HIV infection, and antiretroviral agents devised for its treatment. The viral and host factors that protect against HIV infection and modulate its course, once established, remain to be clarified. HIV infection produces a chronic disease characterized by a primary syndrome, clinical latency period, and manifestations of increasing immunosuppression. It encompasses a wide clinical spectrum ranging from the absence of symptoms to the presence of life-threatening opportunistic diseases. Clinical and laboratory predictors of disease progression have been identified. Neither of the published classification systems for HIV has gained widespread acceptance by the medical community. Staging of patients based on the management implications of their CD4 lymphocyte count is perhaps of greatest practical value to the clinician. PMID- 1594690 TI - FMH-induced decrease in central histamine levels produces increased feeding and body weight in rats. AB - The present study tested the long-term effects of the histamine (H) synthesis inhibitor alpha-fluoromethylhistidine (FMH) on feeding and body weight in rats. FMH (administered via 2-week osmotic minipumps) increased feeding significantly throughout the test period. Body weights were also significantly increased toward the end of the test period. Hypothalamic H assays, performed at the end of the study, confirmed that FMH-treated rats had significantly lower H levels than controls. In general, the results suggest that H activity and feeding are inversely related. PMID- 1594692 TI - AIDS and HIV infection in office practice. PMID- 1594693 TI - Diagnosis and treatment of substance users with HIV infection. AB - Drug users with HIV infection pose an important clinical challenge for primary care practitioners, the provider group that is particularly well situated to supply comprehensive care both for HIV-related conditions and substance-abuse problems. It is important for primary care clinicians to be familiar with the full spectrum of HIV-related disease in drug users, especially concerning bacterial infections, tuberculosis, and sexually transmitted diseases, and with the medical complications of drug use, which may mimic, mask, be obscured by, or simply coexist with HIV-specific conditions. Primary care providers must also be familiar with screening, diagnosis, and treatment of substance-use disorders, and can play a critical role in the identification of drug-use problems and the initiation of drug treatment. An understanding of the special issues of drug interactions, self-medication, and pain management is also important for the care of drug-using patients with HIV infection. Most importantly, providers' awareness of certain common behavioral patterns, problems, and shared concerns among drug users will also help to promote favorable patient outcomes and to minimize frustration and dissatisfaction among clinical staff. PMID- 1594694 TI - Pregnancy and women at risk for HIV infection. AB - Special issues of pregnant women with HIV, such as HIV disease in pregnancy, transmission during pregnancy, transmission through breast milk, the effect of HIV disease on pregnancy outcome, and strategies for preventing neonatal damage from HIV, are discussed. In addition, issues relevant to the care of women in general are presented, including gynecologic manifestations, prevention, and contraception. PMID- 1594695 TI - Adolescents at risk for HIV infection. AB - Although adolescents currently compose fewer than 1% of AIDS cases nationally, they represent an expanding and pivotal population. This article is written for those who currently provide health care for adolescents and for those who will do so in the future. Much of what is known about AIDS in adolescents will be reviewed. Epidemiology, specific risk groups and behavior as well as legal, ethical, educational, and preventive issues unique to adolescents are discussed. In addition, some recommendations and techniques for interviewing teenagers are suggested. PMID- 1594696 TI - Addressing HIV infection in office practice. Assessing risk, counseling, and testing. AB - HIV risk assessment, counseling, and testing performed by primary care physicians can be valuable in the early identification of persons infected with HIV, can contribute to their appropriate medical treatment, and may help to prevent the further spread of the disease. HIV risk assessment comprises a detailed sexual and drug use history, awareness of the mechanisms of HIV transmission, and knowledge of which patients should be encouraged to undergo counseling and testing. During pretest counseling, the physician asks for informed consent for the HIV test, explains the meaning of positive and negative test results, reviews risk behaviors, and offers an appropriate prevention message. During posttest counseling, the physician informs the patient of the results, reviews the meaning of the test results, and reinforces the appropriate prevention messages. Follow up care for seropositive patients should be arranged, including appropriate medical care, referral to social and support services, and, if indicated, mental health care. PMID- 1594697 TI - Health care of the gay male patient. AB - A significant number of men presenting to any primary care physician are gay or have had sexual encounters with members of their own sex. It is important, therefore, that the physician be familiar with particular medical care issues commonly encountered in this population and that she or he also be aware of psychosocial issues that impact on the gay patient's well-being and on the physician's ability to provide competent primary care. PMID- 1594698 TI - Ethical issues. AB - The HIV virus and the associated worldwide pandemic pose enormous biomedical, clinical, and social dilemmas for health care providers, biomedical researchers, policy analysts, and the public at large 10 years after its discovery. Many of these dilemmas and challenges are captured in the difficult ethical issues the HIV epidemic has highlighted for primary care physicians. Given the vanishingly small risk to primary care providers of acquiring HIV infection in office practice and the rapidly increasing prevalence of the virus, a clear ethical obligation to care for HIV-infected patients exists for primary care physicians. Primary care providers should be sensitive to the potentially sensitive nature of patient risk status and HIV testing results and balance confidentiality in the medical record with the "need to know" the patient's clinical status by other health care professionals. Every attempt should be made by the primary care provider to encourage HIV-infected patients to act responsibly toward their intimate sexual partners and inform them of their HIV status to take appropriate precautions against acquiring the virus. Primary care providers should also model responsible shared decision making and goal setting with HIV-infected patients early in the course of the disease, laying the foundation for subsequent decision making later in the course of the illness. Finally, considerable controversy exists about the responsibilities of HIV-infected providers to inform patients of their status; professional and public policy in this area is in rapid flux. Undoubtedly, the HIV epidemic will continue to challenge us and force careful examination of many of the critical dilemmas in modern biomedical ethics. PMID- 1594699 TI - Legal and insurance issues. AB - It is impossible in this space to address all the legal and social issues that attend the care of HIV-seropositive patients. Considerations of access to care, financing of care, testing for HIV, and confidentiality of test results are, however, among the most important. In general, primary care physicians should be willing to contact hospital attorneys or local AIDS activists when social problems arise. They must also realize that often there will be no clear political or legal prescription and that it will be necessary to consult one's own sense of the ethical practice of medicine. PMID- 1594700 TI - Community-based services for people with AIDS. AB - AIDS is a progressively debilitating disease in which the infected individual will require a diverse range and often intensive set of formal and informal services. With assistance from health care providers, community-based organizations, family, and friends, quality of life can be maintained. Community based organizations have the advantages of cost-effectiveness, flexibility, individualized attention, accessibility, and cultural sensitivity. The range of community-based services is described. PMID- 1594701 TI - Supporting health care workers in the treatment of HIV-infected patients. AB - The care of HIV-infected patients is demanding, raising concerns among health care workers regarding safety, competence, and emotional endurance. Many health care workers are reluctant to undertake this challenging work. For many professions within health care, for example nursing, there is a clearly articulated responsibility to treat all ill individuals. Less unanimity on this point continues among physicians. Clearly, a first issue is to continue the discussion of the nature of physicians' professional responsibilities and to convey an understanding of the duties of physicians to medical students and to those considering careers as doctors. Meanwhile, efforts must continue to recruit individuals in all areas of health care to work with HIV-infected people. To some extent, this process will happen as a natural consequence of the evolution of the epidemic and its decreasing geographic and demographic restriction. "Mainstreaming" AIDS care will also require continuing attention to important issues, such as acquiring and maintaining the requisite professional competence in the management of HIV-related illnesses, ensuring the availability of support services that are required for the comprehensive care of HIV complications, and continuing education on and proactive monitoring of infection control practices. All of these activities assist in the creation of a positive environment for the care of AIDS patients. In addition, the emotional consequences of caring for HIV infected people should be directly addressed, although there is less information on which strategies are useful. A supportive working environment, characterized by some meaningful element of control by all health care workers not just the medical staff, nonauthoritarian management, explicit and responsive processes for approaching the inevitable ethical dilemmas that arise in the care of HIV infected patients, and a recognition of the emotional, psychological, and technical aspects of medical care are essential. In such an environment, health care providers will be able to develop and institute programs that address their particular needs. Strategies that have been helpful are diverse and include support groups, rotation of clinical assignments, part-time work, social activities away from the workplace, and collective spiritual activities. PMID- 1594702 TI - Initial clinical assessment and management of HIV infection. AB - Management of HIV infection by the primary care physician can be easily integrated into the usual practice setting. The physician who understands the epidemiology of HIV disease, stays current with basic therapeutic concepts, and knows the patient and his or her living environment is in the best position to help the HIV-infected individual have a constructive and fulfilling life. When the primary care physician has a network of appropriate specialists for consultation and has appropriately integrated office and community-based nonmedical professionals into patient care, the health care team is complete. PMID- 1594703 TI - Evaluation and treatment of later manifestations of HIV infection. AB - An increasing number of primary care physicians will be called on to care for patients with AIDS as the epidemic of HIV infection progresses in the United States. In this article, the more common conditions responsible for significant morbidity and mortality in patients with AIDS have been discussed. It should be apparent that many of these conditions are treatable, either palliatively or with curative intent. Primary care physicians who are familiar with the diagnostic evaluation and therapy of these diseases will therefore be well equipped to provide vital medical care to severely immunocompromised patients with HIV infection. PMID- 1594704 TI - Expanding access to investigational new therapies. AB - One important role for the primary care provider is to be familiar with all available treatment options for HIV disease. Because only a few treatments are approved, unapproved therapy becomes important for many patients. As a result, clinicians have had systems developed that create access to promising investigational drugs. In addition, because of the urgent need to increase the number of proven treatments, some clinicians have chosen to become more directly involved in the evaluation of new treatments for HIV disease by becoming community based "clinician-researchers." PMID- 1594705 TI - The neuropsychiatric aspects of HIV infection. AB - Neuropsychiatric manifestations of HIV infection require aggressive and thorough diagnosis and treatment. Because people may live longer on antiviral therapy and chemoprophylaxis for opportunistic infections, a great emergence of neoplastic challenges to the central nervous system and the possibility of primary HIV encephalopathy appear. Because the mind is the container of all that makes us human, attention to these insults is essential to maintain quality of life, autonomy, and psychologic health as long as possible. Primary care providers can play a major role in this process. New chemotherapeutic interventions will continue to provide hope while longing for a cure or lifelong treatment, containing the tension between realistic optimism and appropriate resignation concerning any one particular individual's condition. Helping patients to see their brain as an organ system that deserves equal attention as the rest of the body is part of the primary provider's role. Finally, when further technologic and pharmacologic interventions are unavailable, the primary care provider serves the most important function by staying by the patient and her or his significant others until the very end of life. PMID- 1594706 TI - Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements during maintenance haloperidol treatment in male patients with schizophrenia. AB - Measurement of plasma prolactin (PRL) concentration and plasma homovanillic acid (HVA) concentration was performed in 24 patients with schizophrenia during maintenance haloperidol treatment. A significant inverse correlation was found between plasma PRL and ratings of both dyskinesia and thought disorder. Plasma PRL was also correlated with negative symptoms. No relationship was found between plasma HVA and any symptom grouping. Twelve patients received an apomorphine challenge; a trend toward a significant inverse relationship was found between baseline dyskinesia and apomorphine-induced decreases in plasma PRL. Plasma PRL and plasma HVA may reflect different elements of dopamine function in the central nervous system during maintenance treatment; plasma PRL may be the useful marker under these conditions. PMID- 1594707 TI - Clinical features of depressed patients who do and do not improve with placebo. AB - The substantial placebo response in depression confounds treatment decisions and the assessment of new therapies. Improvement with placebo occurs infrequently in patients with chronic depression and in those with pituitary-adrenocortical hyperfunction, but other consistent predictors of placebo response have not been detected. We divided 241 moderately to severely depressed patients who had received placebo on a double-blind basis for 3 to 6 weeks into responders (greater than or equal to 50% improvement in Hamilton depression score, final Hamilton depression score less than or equal to 10), extreme nonresponders (less than 25% improvement), and partial responders (all others). Improvement with placebo was associated with a relatively short illness, a precipitating event, depression of only moderate global severity, and a good response to previous antidepressant treatment. These observations suggest that depressed patients who do and do not recover with placebo have different conditions that have not yet been fully characterized. PMID- 1594708 TI - Possible affective-state dependence of the Tridimensional Personality Questionnaire in first-episode psychosis. AB - The authors administered the Tridimensional Personality Questionnaire (TPQ) to 61 patients with first-episode psychosis. Subjects were classified into affective states according to DSM-III-R diagnoses. TPQ scores were compared among these states and correlated with two affective symptom subscales: "mania" and "depression." Manic subjects demonstrated little variation from normative TPQ scores. Compared with findings in manic subjects, the dimensional score for Harm Avoidance was elevated in all affective groups, "worry and pessimism" was elevated in mixed-state subjects, "shyness with strangers" was elevated in depressed and nonaffective subjects, and "attachment" was lower in depressed and nonaffective subjects. The Harm Avoidance dimensional score and two subdimensional scores were positively correlated with the "depression" subscale. The Harm Avoidance dimensional and subdimensional scores showed possible affective-state dependence that may limit the utility of this instrument as a personality measure in first-episode psychosis. PMID- 1594709 TI - Disorders of smooth pursuit eye movement and auditory N100 in schizophrenic patients. AB - Attentional factors are thought to affect eye-tracking patterns. The present study examined the hypothesis that specific quantitative features of eye tracking would be correlated with the amplitude of a component of the auditory evoked potential, the N100, which is known to be enhanced by arousal and selective attention. We studied 12 clinically stable schizophrenic patients by means of DC electro-oculography. The frequency and amplitude of different types of saccades (catchup, backup, anticipatory saccades, and square wave jerks) were assessed. The results suggest that small and large saccades, as classified by a simple amplitude criterion (4 degrees), have differential meanings and indicate that enhanced amplitudes of small saccades are an effect of arousal. PMID- 1594710 TI - Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. AB - Reliable quantitative ratings of chronic medical illness burden have proved to be difficult in geropsychiatric practice and research. Thus, the purpose of the study was to demonstrate the feasibility and reliability of a modified version of the Cumulative Illness Rating Scale (CIRS; Linn et al., 1968) in providing quantitative ratings of chronic illness burden. The modified CIRS was operationalized with a manual of guidelines geared toward the geriatric patient and for clarity was designated the CIRS(G). A total of 141 elderly outpatient subjects (two medical clinic groups of 20 each, 45 recurrent depressed subjects, 21 spousally bereaved subjects, and 35 healthy controls) received comprehensive physical examinations, reviews of symptoms, and laboratory testing. These data were then used by nurse practitioners, physician's assistants, and geriatric psychiatrists to compute CIRS(G) ratings of chronic illness burden. As hypothesized, analysis of variance demonstrated significant differences among groups with respect to total medical illness burden, which was highest among medical clinic patients and lowest in control subjects. Good interrater reliability (i.e., intraclass correlations of 0.78 and 0.88 in a subsample of 10 outpatients and a separate group of 10 inpatients, respectively) was achieved for CIRS(G) total scores. Among medical clinic patients, a significant correlation was found, as expected, between CIRS(G) chronic illness burden and capability as quantified by the Older Americans Activities of Daily Living Scale; and between CIRS(G) scores and physicians' global estimates of medical burden. Finally, with repeated measures of illness burden approximately 1 year from symptom baseline, significant rises were detected, as expected. The current data suggest that the CIRS(G) can be successfully applied in medically and psychiatrically impaired elderly subjects, with good interrater reliability and face validity (credibility). PMID- 1594711 TI - Prolactin bioassay in schizophrenia before and after neuroleptics. AB - Fifteen drug-free schizophrenic male inpatients and 14 normal control subjects were studied. The schizophrenic subjects had a significantly lower ratio of bioassay prolactin to radioimmunoassay prolactin before neuroleptic treatment than they did after treatment. The ratio was lower in the drug-free patients as compared with normal controls. These findings suggest that neuroleptic medications may alter the molecular forms of serum prolactin. The results also suggest that drug-free schizophrenic patients may have a different pattern of prolactin variants than normal subjects and that this difference could be secondary to a disordered tuberoinfundibular dopamine system or long-term effects of neuroleptic drugs. PMID- 1594712 TI - Prediction of relapse of schizophrenic patients: Camberwell Family Interview versus content analysis of verbal behavior. AB - In a replication of the study by Gottschalk et al. (1988), expressed emotion scores derived from the Camberwell Family Interview were compared with Anxiety and Overt Hostility Outward scores from a content analysis of verbal behavior based on a 10-minute speech sample from parents of 49 German schizophrenic inpatients. The scores from the two methods were significantly correlated, but only expressed emotion scores predicted relapse during a 12-month followup. Scores from the Gottschalk-Gleser content analysis did not exceed chance level in prediction of relapse. PMID- 1594713 TI - Schizotypy in partners of patients with schizotypal personality disorders. PMID- 1594714 TI - The patient's perception of the analyst: the hidden transference. AB - Just as the person of the analyst becomes a nidus for the manifestations of transference, so does the analyst's technique. When the patient misperceives person and technique, identifying the transference is not difficult. More complicated are those situations in which the patient's perception of the analyst and of his or her technique is congruent with the analyst's self-representation, or when the patient uses reality aspects of the analysis and the analyst as a resistance. Clinical material from the analysis of three patients is used to illustrate this. PMID- 1594715 TI - Transference: "an original creation". AB - While the psychoanalytic process explores the past, it does so within the context of the immediacy of the present. A clinical vignette is used to demonstrate the distinction between unconscious fantasies which, though buried, are alive in the present, and the historical past which shaped those fantasies. On that basis, interpretations and reconstructions are distinguished. The tension between singular process and dyadic interaction is also considered in the light of the centrality of present experience. Finally, the place of current sensation in connection to memory is addressed. PMID- 1594716 TI - The psychoanalytic view of phobias. Part I: Freud's theories of phobias and anxiety. AB - This paper initiates a series of communications on psychoanalytic and current psychiatric approaches to the understanding and treatment of phobic syndromes with a review and discussion of Freud's evolving ideas on phobias and anxiety. A list of issues that any theory of phobic syndromes must address is compiled on the basis of Freud's work. PMID- 1594717 TI - The psychoanalytic view of phobias. Part II: Infantile phobias. AB - The psychoanalytic literature on infantile phobias, despite disclaimers by several of its prominent authors, seems to demonstrate a growth in knowledge of these conditions and an increasing respect for methodology. It is also noteworthy in its close adherence to the presentation of clinical material. Looking at phobia from this developmental viewpoint has caused us to modify our definition of phobia, adding independence from immediate, fear-provoking stimuli and requiring an inference on the part of the observer because of some integral mental process which is nontransparent. These additions are further specifications of the meaning of the term in general; they are not intended to be limited to infantile phobias. Phobic syndromes can certainly arise well before age four, well before there is any evidence of a child's having entered the oedipal phase of development. Nevertheless, because of the early genital phase, castration reactions, albeit with a somewhat different meaning, usually appear to be involved in the symptom formation. There is also a suggestion that all infantile phobias may begin to arise at this period of development. The symptom pictures in the cases of the children reported in the psychoanalytic literature are very similar. We seem to have described a disorder which, we can hypothesize, has its beginnings in the early genital phase, may emerge as a psychopathological condition at that time, or may reach proportions sufficient to interfere with function or development only several years later. The disorder appears to make use of inherited reflex-like patterns of response to certain stimuli as dangers. On the basis of the reported psychoanalytic experience, we cannot really generalize much about psychogenetics or psychodynamics. Psychoanalysts have applied their ideas about neurotic symptom formation in general to these cases. Just why the illnesses assume these particular forms in these particular children is unclear. The only steps toward specification have been hypotheses introduced by Anna Freud and Owen Renik. Anna Freud hypothesized that a major condensation occurs to focus infantile anxieties on a single symbol, thus causing sharply focused, rather than generalized, anxiety. Renik related self-object differentiation and cognitive development to such "symbolization" in infancy, explaining phobic object formation in terms of primary and secondary process representations and their interaction. Although we have descriptively defined a syndrome "phobia," it is not yet clear whether the disorders of infancy and childhood which fit that definition have significant similarities--descriptively or psychodynamically--with conditions which develop later in life and also appear to fit the descriptive parameters.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1594718 TI - The role of fathers in child and adolescent psychopathology: make room for daddy. AB - This review summarizes research concerning the relation between paternal factors and child and adolescent psychopathology. When compared with mothers, fathers continue to be dramatically underrepresented in developmental research on psychopathology. However, findings from studies of children of clinically referred fathers and nonreferred samples of children and their fathers indicate that there is substantial association between paternal characteristics and child and adolescent psychopathology. Findings from studies of fathers of clinically referred children are stronger for fathers' effects on children's externalizing than internalizing problems. In most cases the degree of risk associated with paternal psychopathology is comparable to that associated with maternal psychopathology. Evidence indicates that the presence of paternal psychopathology is a sufficient but not necessary condition for child or adolescent psychopathology. PMID- 1594719 TI - A developmental model of recipients' reactions to aid. AB - A developmental model of recipients' reactions to aid, which is based on the threat-to-self-esteem model (the dominant theoretical framework in the field), is presented. Various refinements of the threat-to-self-esteem model are proposed to extend its range of applicability and heuristic value to encompass the study of children's reactions to aid. The moderating influences of developmental changes in cognitions regarding self and others, as well as in children's social environment, are examined. Literature from a variety of sources that is relevant to children's reactions to aid, or to processes that may be involved, is reviewed and discussed in light of our model. PMID- 1594720 TI - Interventions for children of divorce: toward greater integration of research and action. AB - A number of child-, family-, and system-focused interventions have been designed to prevent or reduce the negative effects of divorce on children. This article critically evaluates these intervention efforts by examining (a) their relation to basic research on the processes proposed to mediate children's postdivorce adjustment and (b) evaluation studies assessing the effectiveness of various programs. Although interventions address some of the factors proposed to mediate children's adaptation to divorce, the interplay between interventions and basic research on children's postdivorce adaptation is limited. Moreover, some intervention efforts appear to be beneficial, but most lack empirical documentation of their efficacy. This analysis leads to several recommendations for basic and applied research and for improving the response of the mental health field to the problems experienced by many children from divorcing families. PMID- 1594721 TI - Changing AIDS-risk behavior. AB - This article contains a comprehensive, critical review of the acquired immunodeficiency syndrome (AIDS)-risk-reduction literature on interventions that have targeted risky sexual behavior and intravenous drug use practices. A conceptually based, highly generalizable model for promoting and evaluating AIDS risk behavior change in any population of interest is then proposed. The model holds that AIDS-risk reduction is a function of people's information about AIDS transmission and prevention, their motivation to reduce AIDS risk, and their behavioral skills for performing the specific acts involved in risk reduction. Supportive tests of this model, using structural equation modeling techniques, are then reported for populations of university students and gay male affinity group members. PMID- 1594722 TI - Depression and immunocompetence: a review of the literature. AB - Recent evidence suggests that there is a relationship between depression and immunity. On the basis of these studies, it has been argued that depressed mood may increase susceptibility to disease by means of aberrations occurring within the immune system. Empirical research investigating the relationship between depression and immunity is reviewed here. Studies examining both clinical and nonclinical manifestations of depression are discussed and evaluated. This review reveals that indexes of immunocompetence are lower among people exhibiting depressive symptomology and suggests that immune alterations may be more related to dysphoric mood than to specific situations or events. Alternative hypotheses accounting for links between depressed affect and altered immune states are provided, and suggestions for future research are offered. PMID- 1594723 TI - Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. AB - This article considers the role of the hippocampus in memory function. A central thesis is that work with rats, monkeys, and humans--which has sometimes seemed to proceed independently in 3 separate literatures--is now largely in agreement about the function of the hippocampus and related structures. A biological perspective is presented, which proposes multiple memory systems with different functions and distinct anatomical organizations. The hippocampus (together with anatomically related structures) is essential for a specific kind of memory, here termed declarative memory (similar terms include explicit and relational). Declarative memory is contrasted with a heterogeneous collection of nondeclarative (implicit) memory abilities that do not require the hippocampus (skills and habits, simple conditioning, and the phenomenon of priming). The hippocampus is needed temporarily to bind together distributed sites in neocortex that together represent a whole memory. PMID- 1594724 TI - Disorder as harmful dysfunction: a conceptual critique of DSM-III-R's definition of mental disorder. AB - The Diagnostic and Statistical Manual of Mental Disorders (3rd ed., rev.; DSM-III R) operationally defines disorder essentially as "statistically unexpectable distress or disability." This definition is an attempt to operationalize 2 basic principles: that a disorder is harmful and that a disorder is a dysfunction (i.e., an inability of some internal mechanism to perform its natural function). However, the definition fails to capture the idea of "dysfunction" and so fails to validly distinguish disorders from nondisorders, leading to invalidities in many of DSM-III-R's specific diagnostic criteria. These problems with validity are traced to DSM-III-R's strategies for increasing reliability. PMID- 1594725 TI - Learned industriousness. AB - Extensive research with animals and humans indicates that rewarded effort contributes to durable individual differences in industriousness. It is proposed that reinforcement for increased physical or cognitive performance, or for the toleration of aversive stimulation, conditions rewards value to the sensation of high effort and thereby reduces effort's aversiveness. The conditioning of secondary reward value to the sensation of effort provides a dynamic mechanism by which reinforced high performance generalizes across behaviors. Applications to self-control, moral development, and education are described. PMID- 1594726 TI - Stimulus configuration, classical conditioning, and hippocampal function. AB - Hippocampal participation in classical conditioning is described in terms of a multilayer network that portrays stimulus configuration. The network (a) describes behavior in real time, (b) incorporates a layer of "hidden" units positioned between input and output units, (c) includes inputs that are connected to the output directly as well as indirectly through the hidden-unit layer, and (d) uses a biologically plausible backpropagation procedure to train the hidden unit layer. Nodes and connections in the neural network are mapped onto regional cerebellar, cortical, and hippocampal circuits, and the effect of lesions of different brain regions is formally studied. Computer simulations of the following classical conditioning paradigms are presented: acquisition of delay and trace conditioning, extinction, acquisition-extinction series of delay conditioning, blocking, over-shadowing, discrimination acquisition, discrimination reversal, feature-positive discrimination, conditioned inhibition, negative patterning, positive patterning, and generalization. The model correctly describes the effect of hippocampal and cortical lesions in many of these paradigms, as well as neural activity in hippocampus and medial septum during classical conditioning. Some of these results might be extended to the description of anterograde amnesia in human patients. PMID- 1594727 TI - Levels of aggregation and the generalized matching law. AB - Concurrent operant behavior is often described using molar response tendencies measured over many sessions. In contrast, other models relate the allocation of behavior to momentary or molecular processes that operate over shorter periods. In this article, a formal model of the statistical properties of molecular behavioral matching is developed. Molar matching is the result when many individual bouts of responding are aggregated. However, behavioral allocation at the molecular level will differ from the molar result. The model indicates that aggregation effects should be controlled in analyses of matching and that the comparison of molecular theories of concurrent operant behavior with molecular models of matching performance affords ideographic analyses of choice behavior. PMID- 1594728 TI - Processing implicit and explicit representations. AB - This article summarizes the results of a 15-year research program dedicated to understanding how implicitly activated memories affect remembering and proposes a model for describing such influences. Implicit memories are manipulated by varying the number of associates preexperimentally linked to test cues or to studied words. Assumptions of the model specify when implicit memories of various types are likely to contribute to performance in various tasks. The main assumptions are that encoding involves both explicit and implicit processing components and that these components provide mutually exclusive sources of information during testing. Experiments designed to evaluate the exclusivity assumption are reported, and implications of the findings for several theoretical frameworks are discussed. PMID- 1594729 TI - Using sound to solve syntactic problems: the role of phonology in grammatical category assignments. AB - One ubiquitous problem in language processing involves the assignment of words to the correct grammatical category, such as noun or verb. In general, semantic and syntactic cues have been cited as the principal information for grammatical category assignment, to the neglect of possible phonological cues. This neglect is unwarranted, and the following claims are made: (a) Numerous correlations between phonology and grammatical class exist, (b) some of these correlations are large and can pervade the entire lexicon of a language and hence can involve thousands of words, (c) experiments have repeatedly found that adults and children have learned these correlations, and (d) explanations for how these correlations arose can be proposed and evaluated. Implications of these phenomena for language representation and processing are discussed. PMID- 1594730 TI - Covariation in natural causal induction. AB - The covariation component of everyday causal inference has been depicted, in both cognitive and social psychology as well as in philosophy, as heterogeneous and prone to biases. The models and biases discussed in these domains are analyzed with respect to focal sets: contextually determined sets of events over which covariation is computed. Moreover, these models are compared to our probabilistic contrast model, which specifies causes as first and higher order contrasts computed over events in a focal set. Contrary to the previous depiction of covariation computation, the present assessment indicates that a single normative mechanism--the computation of probabilistic contrasts--underlies this essential component of natural causal induction both in everyday and in scientific situations. PMID- 1594731 TI - Addressing the measles epidemic. PMID- 1594732 TI - The Public Health Service action plan to improve access to immunization services. The Interagency Committee to Improve Access to Immunization Services. AB - The Public Health Service's Interagency Committee to Improve Access to Immunization Services (ICI) has responsibility for improving the immunization protection of the nation's children and other vulnerable populations. ICI's Action Plan to Improve Access to Immunization Services sets 14 goals with 120 action steps for improving immunization services nationwide by (a) increasing coordination among Federal health, income, housing, education, and nutrition programs; (b) reducing policy and management barriers that limit access to delivery systems, and (c) strengthening the delivery infrastructure. To accomplish the goals of the plan, there is a $72.0 million increase in funding appropriated in fiscal year 1992 specifically for this purpose. The President's Budget for fiscal year 1993 includes a $24.5 million increase for continued program implementation. The additional resources will be used to address delivery and access problems, which have been determined to be the primary factors limiting immunization for many children. PMID- 1594733 TI - Six areas lead national early immunization drive. AB - On June 13, 1991, President George Bush announced in a White House ceremony a local planning effort to break down barriers and provide better access to immunization in six representative localities "to solve the problem of late immunization." (children need to be immunized appropriately by their second birthday, not just in time for school.). The community "Immunization Action Plans" (IAP) are one of several Federal, State, and local responses to an outbreak of measles that produced 27,600 cases and 89 deaths in 1990. The community effort and subsequent early childhood immunization plans around the country are also part of a much broader effort initiated by Secretary Sullivan as a Healthy People Year 2000 goal to increase immunization levels to at least 90 percent for the nation's children by their second birthday. These efforts also respond to 13 recommendations for improving immunization availability made by the National Vaccine Advisory Committee in January 1991. The recommendations focused on improvements in the management of immunization delivery and in methods for measuring immunization status, increasing appropriate consumer demand, and other prevention needs. Although measles prompted the action, the immunization initiative is aimed also at eight other communicable childhood diseases- diphtheria, tetanus, pertussis or whooping cough, poliomyelitis, mumps, rubella, and Haemophilus influenza type b that causes bacterial meningitis, and hepatitis B. Details are described of the immunization action plans developed by Dallas, TX; Maricopa County (Phoenix), AZ; South Dakota; Detroit, MI; San Diego, CA; and Philadelphia, PA, to ensure that children are fully immunized not just by the time they enter school but by age 2 years. The six were chosen by the Centers for Disease Control as representative of many without adequate childhood immunization coverage. PMID- 1594734 TI - Applying total quality management concepts to public health organizations. AB - Total quality management (TQM) is a participative, systematic approach to planning and implementing a continuous organizational improvement process. Its approach is focused on satisfying customers' expectations, identifying problems, building commitment, and promoting open decision-making among workers. TQM applies analytical tools, such as flow and statistical charts and check sheets, to gather data about activities within an organization. TQM uses process techniques, such as nominal groups, brainstorming, and consensus forming to facilitate communication and decision making. TQM applications in the public sector and particularly in public health agencies have been limited. The process of integrating TQM into public health agencies complements and enhances the Model Standards Program and assessment methodologies, such as the Assessment Protocol for Excellence in Public Health (APEX-PH), which are mechanisms for establishing strategic directions for public health. The authors examine the potential for using TQM as a method to achieve and exceed standards quickly and efficiently. They discuss the relationship of performance standards and assessment methodologies with TQM and provide guidelines for achieving the full potential of TQM in public health organizations. The guidelines include redefining the role of management, defining a common corporate culture, refining the role of citizen oversight functions, and setting realistic estimates of the time needed to complete a task or project. PMID- 1594735 TI - Blue Thursday? Homicide and suicide among urban 15-24-year-old black male Americans. AB - A comparative analysis was made of day of the week variations in homicide and suicide deaths among 15-24-year-old white males, black males, white females, and black females in the 22 counties with the most black persons in the United States. Thirty-seven percent of black Americans and 14 percent of white Americans lived in these densely populated counties. The authors expected a weekend excess of homicide and a Monday excess of suicide. They found a pronounced excess of homicides on weekends, especially among white males. A slight excess of suicide was observed on Monday, but other slight excesses of suicide were also found. Young black males exhibited an unexpected excess of homicides and suicides on Thursday. On Thursdays the black male-white male ratio for homicide was 1.43 and for suicide, 1.26. Possible explanations for the young black males' blue Thursday phenomenon are offered. PMID- 1594736 TI - Estimating the probability of spontaneous abortion in the presence of induced abortion and vice versa. AB - An integrated approach to estimate the total number of pregnancies that begin in a population during one calendar year and the probability of spontaneous abortion is described. This includes an indirect estimate of the number of pregnancies that result in spontaneous abortions. The method simultaneously takes into account the proportion of induced abortions that are censored by spontaneous abortions and vice versa in order to estimate the true annual number of spontaneous and induced abortions for a population. It also estimates the proportion of pregnancies that women intended to allow to continue to a live birth. The proposed indirect approach derives adjustment factors to make indirect estimates by combining vital statistics information on gestational age at induced abortion (from the 12 States that report to the National Center for Health Statistics) with a life table of spontaneous abortion probabilities. The adjustment factors are applied to data on induced abortions from the Alan Guttmacher Institute Abortion Provider Survey and data on births from U.S. vital statistics. For the United States in 1980 the probability of a spontaneous abortion is 19 percent, given the presence of induced abortion. Once the effects of spontaneous abortion are discounted, women in 1980 intended to allow 73 percent of their pregnancies to proceed to a live birth. One medical benefit to a population practicing induced abortion is that induced abortions avert some spontaneous abortions, leading to a lower mean gestational duration at the time of spontaneous abortion. PMID- 1594737 TI - Cancer prevention counseling on telephone helplines. AB - Since 1983, the National Cancer Institute (NCI) has collected data by means of its Cancer Information Service (CIS), a toll-free telephone helpline for health care professionals and members of the public who have questions about cancer treatment, diagnosis, and prevention. These data reveal information about the characteristics of callers and their questions and about how inquiries reflect mass media promotions and secular trends. A request for a publication is the most common type of inquiry, followed by information about specific cancer sites, smoking prevention and cessation, other types of prevention, cancer treatment, cancer symptoms, referrals to physicians, NCI clinical trials, hospital and clinic-based screening programs, and general counseling or coping. Breast cancer is the most common cancer of interest, followed by respiratory system cancers, colon and prostate cancers, leukemia, melanoma, nonHodgkin's lymphoma, cervical cancer, general or unspecified skin cancer, and ovarian cancer. Responding to these other caller inquiries, CIS counselors may proactively guide callers to a desirable goal, such as screening mammography. Protocols have been developed to assist counselors' proactive efforts, and preliminary results are beginning to support this approach. The findings gathered in this study underscore the health education potential of telephone helplines and point to the need for controlled evaluation research on the effectiveness of proactive counselor advice. PMID- 1594738 TI - Predicting and reinforcing children's intentions to wear protective helmets while bicycling. AB - The researchers undertook to identify the factors that are most likely to influence children's intentions to use bicycle helmets. To determine the most important intention influencing factors, a random sample of 797 students in grades 4 through 6 completed a self-administered questionnaire concerning their beliefs about helmet use. They were asked about their perceptions of the risk of riding bicycles unprotected, the severity of possible head injuries, and about other bicycle-safety related behaviors. Factors that best predicted the student's intentions to use bicycle helmets involved both behavioral beliefs and normative beliefs. Analysis of factors influencing those with low intentions to use helmets, compared to those with high intentions, suggests the most effective messages that health planners can provide preadolescents to influence them to use helmets. They are that helmet use is fun and attractive, helmets provide a new look and a sporting image, and friends approve of and value this behavior. Parents, and particularly mothers, can reinforce their children's intentions to use helmets and their involvement should be encouraged. PMID- 1594739 TI - Predicting needs for special education resources for mental retardation from birth defects records. AB - Planning of service delivery systems for children with special health care needs would be enhanced by knowledge of numbers of cases anticipated in defined geographic areas. A method is described for predicting numbers of children who will likely have mental retardation sufficient to require special education services, based on the birth prevalence of birth defects and clinicians' estimates of the likelihood of mental retardation associated with each specific birth defect. This method is applied to the 1980-82 birth cohort of a 28-county area of south and central Arkansas, and it is compared with special education enrollment data for children ages 6 to 8 in academic year 1988-89. According to this estimate, children with birth defects may account for 32 to 56 percent of the cases of mental retardation among 6- to 8-year-olds reported by the public schools. PMID- 1594740 TI - Improving health care communication for persons with mental retardation. AB - There has been little effort directed at training health care professionals in behaviors and attitudes that are effective in communicating with persons with mental retardation. Such training would be beneficial not only to assist those with congenital cognitive deficits but for those with acquired central nervous system conditions as well, for example, dementia. Persons with mental retardation are living in community settings in greater numbers and increasingly participating in vocational, residential, and health care programs. Yet, most health care professionals are not routinely offered an opportunity to gain experience interacting with people who have limited ability to express and understand health care information. An education program was focused on health care professionals' use of basic communication skills when providing health information to an adult who is mentally retarded. A self-study instructional text and a 20-minute companion video provided methods of communicating with a patient with mental retardation in medical and dental care settings. Resident physicians, medical students, nurses, and nursing assistants improved their communication skills, knew more about mental retardation, and were more proactive in health care interviews following training. Health care training needs to incorporate educational opportunities focusing on skills to assist special populations. Brief, structured, and interactive skill training in communication offered early in the health care professional's career has positive benefits for the recipient and the provider. PMID- 1594741 TI - The nutritional status and dietary adequacy of single homeless women and their children in shelters. AB - Data were collected on the nutrient intake and nutritional status of 96 single mothers and their 192 dependent children who had been displaced from their homes. The objective of the study was to provide information on the dietary adequacy of a newly identified subgroup of homeless persons, single women and their dependent children. Once situated in temporary housing, those participating in the study indicated that they believed that they were receiving sufficient food. However, a nutrient analysis found that the study subjects in all age groups were consuming less than 50 percent of the 1989 Recommended Dietary Allowances (RDA) for iron, magnesium, zinc, and folic acid. Adults were consuming less than 50 percent of the RDA for calcium. The type and amounts of fats consumed were in higher than desirable quantities for a significant number of subjects of all ages. The health risk factors of iron deficiency anemia, obesity, and hypercholesterolemia were prevalent. The findings indicate a need to examine and remedy nutrient intake deficiencies among single women who are heads of household and their dependent children in temporary housing situations. Diet-related conditions found included low nutrient intakes that may affect child growth and development, risk factors associated with chronic disease, and lack of appropriate foods and knowledge of food preparation methods in shelter situations. Applicable, understandable nutrition education should be offered mothers in shelter situations to help them make food choices at the shelter and when they become self-sufficient. Assistance programs such as the Special Supplemental Food Program for Women, Infants, and Children, and food stamps, should be available to this group. PMID- 1594742 TI - A seasonal association between SIDS deaths and kindergarten absences. AB - Data from linked birth and death certificates from the State of Oregon were used to determine the monthly distribution of deaths from sudden infant death syndrome (SIDS) for the years 1976 through 1984. The monthly number of SIDS deaths increased in winter and decreased in summer, when schools usually are not in session. Absences from kindergarten were determined from school records for the period 1979-84. School absences, previously shown to reflect incidence of predominantly infectious diseases, were found to be positively correlated with occurrences of SIDS. The role of ordinarily nonlethal infections in occurrences of SIDS has been established by history, histology, and viral isolation. The authors concluded that the seasonality of SIDS is related to the seasonality of respiratory infections and that the seasonality is influenced by respiratory infections being spread from school children to infants during periods when schools are in session. PMID- 1594743 TI - Detecting colorectal cancer with a large scale fecal occult blood testing program. AB - The researchers analyzed outcome data for 439 persons who had positive fecal occult blood tests in a 1984 statewide program for Connecticut residents. Among those with positive test results, colorectal cancer was diagnosed in 33 persons, 7.5 percent of the sample, during 3.5 years of follow-up. More than one-half of all cases found, 15 of 29 persons, or 52 percent, were diagnosed with in-situ or localized tumors, which are most likely to be treated successfully. The predictive value of a positive test varied according to the screened person's age and the number of positive tests obtained from that person. Among those 60 years or older, the positive predictive value of the screening test was 9 percent, compared to 3 percent for persons younger than 60 years. Having more than one positive test was associated with a positive predictive value of 12 percent, compared to 5 percent for one positive test. The findings support the use of fecal occult blood testing for early detection of colorectal cancer. PMID- 1594744 TI - Attitudes of patients toward smoking by health professionals. AB - Do the smoking behaviors of physicians and nurses affect patients' perceptions of the trust and effectiveness of these health professionals? In this exploratory study, a 40-item questionnaire was given to patients discharged from an Air Force hospital during a 4-week period. The survey resulted in 116 usable questionnaires from 40 patients who had never smoked, 44 who no longer smoked, and 32 who still smoked. Analyses of variance in the replies to the questionnaire indicated that nonsmokers felt strongly about health professionals not modeling unhealthy behaviors, while smokers indicated they had no opinion. Regarding the relationship between the smoking habits of physicians and nurses and patients' perceptions of trust and effectiveness, smokers felt strongly there was no relationship, whereas nonsmokers indicated no opinion. A review of the literature suggested that, on the average, health professionals who smoke may not be as effective in counseling patients to quit smoking as health professionals who do not smoke. Health professionals who smoke have the potential to affect unintentionally the smoking behaviors of others through modeling. PMID- 1594745 TI - Urban Indians' smoking patterns and interest in quitting. AB - Little is known about smoking patterns of urban American Indians and their interest in quitting. Most published research has focused upon American Indians who live on rural reservations. In this study, personal interviews were conducted with a convenience sample of patients at Urban Indian Health Clinics in four geographically diverse sites: Milwaukee, WI, Minneapolis, MN, and Seattle and Spokane, WA. A total of 419 current smokers and 173 ex-smokers completed interviews. Current smokers reported a median cigarette consumption of 11 per day. Smokers indicated both a moderate desire to quit (mean 5.97, on a scale 0 10) and moderate confidence in their ability to do so (mean 5.56, on a scale 0 10). More than 70 percent of current smokers indicated having previously tried to quit. The most common reasons cited for relapse included craving, social situations, stress, and nervousness. The most common reasons for quitting given by ex-smokers included being "sick" of smoking, health concerns, respiratory problems, and pregnancy. The estimated quit-ratio (former smokers divided by current+former smokers) was 29.7 percent. This quit-ratio, although substantial, is lower than the 45 percent quit-ratio reported for the general U.S. population. Perhaps the most striking findings are the similarities between American Indians and the overall population in both interest in quitting and reasons for doing so. Smoking cessation previously has been viewed as a low priority for this population. The current results suggest the viability of systematic efforts to encourage urban American Indians to quit smoking. PMID- 1594747 TI - A national agenda for helping homeless mentally ill people. PMID- 1594746 TI - Awareness and use of blood cholesterol tests in 40-74-year-olds by educational level. AB - Questions on awareness, use, and results of blood cholesterol tests were included in telephone surveys on cancer conducted in 1988 on random samples of persons 40 74 years of age in Long Island, NY (N = 440), and in Connecticut (N = 453). Educational level was significantly and positively associated with the proportions reporting ever having heard of blood cholesterol tests, ever having had a test done ("by a doctor"), and having a recent test, 1987-88, but not with the proportion reportedly having been told by a doctor that their cholesterol level was "high." In multivariate analyses, greater education (college graduate versus all others) and greater frequency of medical checkups (annual versus other) were significant independent predictors of ever having had a cholesterol test or having been tested in 1987 or 1988. Implications of findings were discussed with regard to monitoring changes over time in awareness and use of cholesterol tests according to educational level and to planning interventions aimed at less educated groups. PMID- 1594748 TI - Impact of a local ordinance banning tobacco sales to minors. AB - Most addictions to tobacco begin when a person is younger than age 18. Although the sale of tobacco to minors is illegal in most jurisdictions, there is often little enforcement of these laws, and minors can usually purchase tobacco easily. The impact of a local ordinance designed to prevent tobacco sales to minors was assessed by surveys of 10th grade students before and after the implementation of the ordinance. Tobacco use declined from 25.3 percent to 19.7 percent overall, with a significant (P = 0.004) decline from 26.4 percent to 11.5 percent among girls. There was also a significant (P = 0.008) increase from 29.3 percent to 61.5 percent in the proportion of students reporting they were asked for proof of age when they attempted to purchase tobacco. Local ordinances may be an effective tool for reducing tobacco use by adolescents. PMID- 1594749 TI - 37 AIDS clinical trials units funded by NIAID. PMID- 1594751 TI - Prescriptive authority for nurse specialists. PMID- 1594750 TI - States, cities receive more than $155 million in AIDS-HIV funding. PMID- 1594752 TI - New insurance for healthcare workers exposed to HIV. PMID- 1594753 TI - Radiation-induced increase in expression of the alpha IIb beta 3 integrin in melanoma cells: effects on metastatic potential. AB - We investigated the effects of nonlethal gamma radiation on the metastatic potential of the murine tumor cell line, B16 melanoma. The ability of B16 cells to adhere to fibronectin, which is in part mediated by the alpha IIb beta 3 integrin receptor, is predictive of metastatic potential. We determined that exposure to 0.25-2.5 Gy gamma radiation significantly enhanced B16 cell adhesion to fibronectin. The radiation-enhanced adhesion was dependent on enhanced expression of the alpha IIb beta 3 integrin. We observed that 15 min after 0.5 Gy radiation, 99% of irradiated B16 tumor cells were positively labeled with monoclonal antibodies directed against alpha IIb beta 3 compared to 22% of sham irradiated cells. Radiation-enhanced expression of the alpha IIb beta 3 receptor is reversible and down-regulation begins within 2-4 h postirradiation. Finally, we found that irradiation significantly enhanced the ability of B16 cells to form metastases in a lung colony assay. It is concluded that a relationship exists between radiation effects on the B16 tumor cells, alpha IIb beta 3 receptor expression, adhesion in vitro, and metastasis in vivo. We suggest that low-dose radiation, at levels comparable to those used in fractionated or hyperfractionated radiotherapy, may alter the metastatic phenotype and potential of surviving tumor cells via a rapid alteration in their surface expression of alpha IIb beta 3 integrin receptors. PMID- 1594754 TI - The sensitivity of quiescent and proliferating mouse spermatogonial stem cells to X irradiation. AB - The radiosensitivity of spermatogonial stem cells to X rays was determined in the various stages of the cycle of the seminiferous epithelium of the CBA mouse. The numbers of undifferentiated spermatogonia present 10 days after graded doses of X rays (0.5-8.0 Gy) were taken as a measure of stem cell survival. Dose-response relationships were generated for each stage of the epithelial cycle by counting spermatogonial numbers and also by using the repopulation index method. Spermatogonial stem cells were found to be most sensitive to X rays during quiescence (stages IV-VII) and most resistant during active proliferation (stages IX-II). The D0 for X rays varied from 1.0 Gy for quiescent spermatogonial stem cells to 2.4 Gy for actively proliferating stem cells. In most epithelial stages the dose-response curves showed no shoulder in the low-dose region. PMID- 1594755 TI - The sensitivity to X rays of mouse spermatogonia that are committed to differentiate and of differentiating spermatogonia. AB - In the CBA mouse the radiosensitivity of the undifferentiated spermatogonia that are committed to differentiate was determined by counting their more developed descendants 10 days after graded doses of X rays. Decreasing D0 values were found when these differentiating spermatogonia were derived from undifferentiated spermatogonia that were located in all likelihood in chains of increasing length. In stages IX and X of the epithelial cycle the radiosensitivity of these undifferentiated spermatogonia was characterized by a D0 of 2.2 Gy. This D0 value most likely belongs to the Asingle spermatogonia that form repopulating colonies which give rise to differentiating spermatogonia within the same epithelial cycle. In stages XII/I, where a D0 of 1.0 Gy was found, the dose-response curve is likely dominated by the Apaired spermatogonia present in these stages. In stages III to VII, the Aaligned spermatogonia transforming into A1 spermatogonia determine the radiosensitivity. During this period the D0 decreased from 0.7 to 0.4 Gy. Differentiating A1 to A3 and B spermatogonia had rather similar radiosensitivities of 0.4 to 0.5 Gy. PMID- 1594756 TI - Differential sensitization of human tumor cells by ara-A to X irradiation and its relationship to inherent radioresponse. AB - We have previously shown that pretreatment of plateau-phase cultures of human tumor cells with ara-A can markedly sensitize them to the cytotoxic effects of X irradiation; the degree of sensitization varied in two different cell lines. The present study was undertaken to determine whether variability in radiosensitization by ara-A occurs at random in human tumor cell lines or if it is related to their intrinsic radiosensitivity (human tumor radioresponse). The interaction between ara-A and X irradiation was examined in plateau-phase cultures of early-passage tumor cell lines of varying radioresponse (D0 range 0.85-3.15 Gy) subcultured immediately after irradiation to measure survival. In six of the eight cell lines studied, pretreatment with ara-A greatly enhanced the lethal effects of X irradiation in a concentration-dependent fashion. Little or no effect was observed in the two radiosensitive cell lines. When ara-A sensitization was plotted as a function of D10 or D, a linear relationship was observed. These data suggest that pretreatment with ara-A is effective in sensitizing radiation-resistant human tumor cells to the lethal effects of X rays, and that this phenomenon may be dependent upon inherent tumor cell radiosensitivity. PMID- 1594757 TI - Variation in radiation-induced formation of DNA double-strand breaks as a function of chromatin structure. AB - The influence of chromatin structure on induction of DNA double-strand breaks (DSBs) by X radiation was studied in DNA from CHO cells. Whole cells, nuclei with condensed or relaxed chromatin, and deproteinized DNA in agarose plugs were irradiated and DSB formation was measured as a decrease in the length of DNA by nondenaturing, pulsed-field, agarose gel electrophoresis. The yield of DSBs in deproteinized DNA (2.3 x 10(-10) DSBs Da-1 Gy-1) was observed to be 70 times greater than the yield of DSBs (3.1 x 10(-12) DSBs Da-1 Gy-1) observed in DNA in the intact cell nucleus. Organization of DNA into the basic nucleosome repeat structure and condensation of the chromatin fiber into higher-order structure protected DNA from DSB induction by factors of 8.3 and 4.5, respectively. An additional twofold protection of DNA in fully condensed chromatin occurred in the intact cell nucleus. Since this protection did not appear to involve chromatin structure, we speculate that this additional protection may result from the association of soluble protein and nonprotein sulfhydryls with DNA in the intact cell nucleus. The results are consistent with the organization of nuclear DNA into both basic nucleosome repeat structure and higher-order chromatin structure providing significant protection against DSB induction. PMID- 1594758 TI - Diatom response to extremely low-frequency magnetic fields. AB - Reports that extremely low-frequency magnetic fields can interfere with normal biological cell function continue to stimulate experimental activity as well as investigations into the possible mechanism of the interaction. The "cyclotron resonance" model of Liboff has been tested by Smith et al. (Bioelectromagnetics 8, 215-227, 1987) using as the biological test system the diatom Amphora coffeiformis. They report enhanced motility of the diatom in response to a low frequency electromagnetic field tuned to the cyclotron resonance condition for calcium ions. We report here an attempt to reproduce their results. Following their protocol diatoms were seeded onto agar plates containing varying amounts of calcium and exposed to colinear DC and AC magnetic fields tuned to the cyclotron resonant condition for frequencies of 16, 30, and 60 Hz. The fractional motility was compared with that of control plates seeded at the same time from the same culture. We find no evidence of a cyclotron resonance effect. PMID- 1594759 TI - Mutation spectrum in gamma-irradiated shuttle vector replicated in ataxia telangiectasia lymphoblasts. AB - Cells from ataxia-telangiectasia (AT) patients are hypersensitive to the lethal effects of ionizing radiation. To assess radiation mutagenesis in these cells, the SV40-based shuttle vector, pZ189, was used to analyze gamma-ray-induced mutations following the plasmid's replication in AT lymphoblasts. Progenies from the AT line GM2783 exposed to 50 Gy showed a mutation frequency of 7.6 x 10(-3), 63-fold over background; surviving plasmids were 3.4% of control. Both values were essentially the same as those of irradiated plasmids replicated in a normal lymphoblast line, GM606. In addition, pZ189 exposed to 25 Gy of gamma radiation and replicated in another normal lymphoblast line and in cells of two additional AT lymphoblast lines showed similar mutation frequencies and percentages of surviving plasmids. Qualitative comparison of plasmid mutations from AT and normal cells showed no significant differences, indicating that the damaged DNA was repaired with similar fidelity in AT and normal cells. These studies suggest that there is no correlation between the enhanced sensitivity of AT cells to killing by ionizing radiation and gamma-radiation-induced mutagenesis of plasmid DNA processed in these cells. PMID- 1594760 TI - Cellular proto-oncogene expression following exposure of mice to gamma rays. AB - Many studies have shown the importance of altered cellular proto-oncogene expression in contributing to changes in cell survival, cell transformation, and cell cycle progression. In these experiments we examined the effects of total body exposure of BCF1 mice to gamma rays (3 Gy) in modulating expression of cellular oncogenes in both gut and liver tissues. We selected specific cellular oncogenes (c-fos, c-myc, c-src, and c-H-ras), based on their normal expression in liver and gut tissues from untreated mice. As early as 5 min following whole-body exposure of BCF1 mice to gamma rays we detected induction of mRNA specific for c src and c-H-ras in both liver and gut tissues. Accumulation of c-fos-RNA was slightly decreased in gut but was unaffected in liver tissue from irradiated mice relative to untreated controls. Accumulation of c-myc mRNA was unaffected in all tissues examined. These experiments document that modulation of cellular proto oncogene expression can occur as an early event in tissues following irradiation and suggest that this modulation may play a role in radiation-induced cellular changes. PMID- 1594761 TI - Effects of bradykinin on the hemodynamics of tumor and granulating normal tissue microvasculature. AB - Bradykinin (BK) is an important endogenous mediator of microvascular flow modulation. Since the structure of the microcirculation is very different in tumor tissues than in normal tissues, bradykinin may elicit different responses in tumors. This study was designed to test the hypothesis that local administration of bradykinin increases blood flow preferentially in normal tissue relative to adjacent tumor tissue, resulting in a "vascular steal" phenomenon. Microvessel diameters (D), velocities (Vc), length densities, shear rates, and intermittent flow frequencies were measured every 10 min before, during, and after 40 min exposure to BK in rats with dorsal flap window chambers 9 days after tumor implantation. Separate studies were made of normal vessels outside the tumor margin, the hypervascular tumor periphery, and the tumor center. Bradykinin was administered with a suffusion medium flowing over the tissue at 1-2 ml/min with a BK concentration of 1.6 x 10(7) M. Administration of BK created five distinct changes in normal and tumor vessel function that varied over time, but coincidentally reached a maximum effect after 20 min exposure to BK. In normal vessels, increased Vc and D led to increased flow, which reached a peak 20 min after onset of suffusion with BK. In contrast, in centrally located tumor vessels, decreased D and Vc were observed in most vessels during the initial 10 20 min of suffusion. In addition, there was a significant increase in intermittent flow frequency in tumor central vessels, which peaked after 20 min of suffusion with BK. These five separate observations that coincided at 20 min of suffusion are consistent with a "vascular steal" phenomenon. The increase in normal microvessel D and Vc at 20 min suggests that BK causes vasodilation in arterioles. The coincident decrease in tumor microvessel D and Vc suggests that tumor feeding vessels are less able to respond to BK by vasodilating. The concomitant increase in intermittent flow frequency in tumor vessels suggests that a reduction in pressure drop occurred after 20 min exposure to BK, which is also consistent with "vascular steal." Since BK is also known to increase vascular permeability, it is possible that increases in interstitial fluid pressure brought on by exposure to BK contributed to the observed reduction in tumor blood flow. In normal vessels, reduced D and Vc, relative to peak values, were noted after 40 min suffusion with BK. Adherence of leukocytes to the vessel walls was prominent and microthrombi were also observed during this period. No evidence of such adhesion was seen in tumor vessels, although microthrombi were observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1594762 TI - Microdosimetry for boron neutron capture therapy. AB - Preclinical studies for boron neutron capture therapy (BNCT) using epithermal neutrons are ongoing at several laboratories. The absorbed dose in tumor cells is a function of the thermal neutron flux at depth, the microscopic boron concentration, and the size of the cell. Dosimetry is therefore complicated by the admixture of thermal, epithermal, and fast neutrons, plus gamma rays, and the array of secondary high-linear-energy-transfer particles produced within the patient from neutron interactions. Microdosimetry can be a viable technique for determining absorbed dose and radiation quality. A 2.5-cm-diameter tissue equivalent gas proportional counter has been built with 50 parts per million (ppm) 10B incorporated into the walls and counting gas to simulate the boron uptake anticipated in tumors. Measurements of lineal energy (y) spectra for BNCT in simulated volumes of 1-10 microns diameter show a dose enhancement factor of 4.3 for 30 ppm boron, and a "y" of 250 keV/microns for the boron capture process. Chamber design plus details of experimental and calculated linear energy spectra will be presented. PMID- 1594763 TI - Radioprotection of hematopoietic tissues in mice by lipoic acid. AB - Lipoic acid is a lipophilic antioxidant that participates in many enzymatic reactions and is used clinically to treat mushroom poisoning and metal toxicity. In this report the protective effect of lipoic acid (oxidized form) against radiation injury to hematopoietic tissues in mice was assessed by the endogenous and exogenous spleen colony assays and survival (LD50/30) assay. Intraperitoneal administration of lipoic acid at a nonlethal concentration of 200 mg/kg body wt, 30 min before irradiation increased the LD50/30 from 8.67 to 10.93 Gy in male CD2F1 mice. Following a 9-Gy irradiation, the yield of endogenous spleen colony forming units in mice treated with saline and lipoic acid was 0.75 +/- 0.5 and 8.9 +/- 1.6, respectively. Using the exogenous spleen colony assay, lipoic acid treatment increased the D0 from 0.81 +/- 0.01 to 1.09 +/- 0.01 Gy, yielding a dose modification factor of 1.34 +/- 0.01. Dihydrolipoic acid (reduced form) has no radioprotective effect in CD2F1 mice. PMID- 1594764 TI - Increased resistance to ionizing and ultraviolet radiation in Escherichia coli JM83 is associated with a chromosomal rearrangement. AB - Cells cope with radiation damage through several mechanisms: (1) increased DNA repair activity, (2) scavenging and inactivation of radiation-induced radical molecules, and (3) entry into a G0-like quiescent state. We have investigated a chromosomal rearrangement to elucidate further the molecular and genetic mechanisms underlying these phenomena. A mutant of Escherichia coli JM83 (phi 80dlacZ delta M15) was isolated that demonstrated significantly increased resistance to both ionizing and ultraviolet radiation. Surviving fractions of mutant and wild-type cells were measured following exposure to standardized doses of radiation. Increased radioresistance was directly related to a chromosomal alteration near the bacteriophage phi 80 attachment site (attB), as initially detected by the LacZ- phenotype of the isolate. Southern hybridization of chromosomal DNA from the mutant and wild-type E. coli JM83 strains indicated that a deletion had occurred. We propose that the deletion near the attB locus produces the radioresistant phenotype of the E. coli JM83 LacZ- mutant, perhaps through the alteration or inactivation of a gene or its controlling element(s). PMID- 1594765 TI - Hyperparathyroidism among atomic bomb survivors in Hiroshima. AB - To determine the effect of exposure to atomic bomb radiation on the occurrence of hyperparathyroidism, the prevalence was determined among a population of 3,948 atomic bomb survivors and their controls in Hiroshima. The diagnosis of hyperparathyroidism was based upon histopathological findings or the presence of consistent hypercalcemia and elevated levels of serum parathyroid hormone. Primary hyperparathyroidism was diagnosed in 19 persons (3 males, 16 females). Females had approximately a threefold higher overall prevalence of hyperparathyroidism than males (P less than 0.05). The prevalence rates of hyperparathyroidism increased with radiation dose (chi2(1) = 12, P less than 0.001) after adjusting for sex and age at the time of the bombing. The estimated relative risk was 4.1 at 1 Gy (95% confidence limits 1.7 to 14). There was some evidence that the effect of radiation was greater for individuals who were younger at the time of the bombing. In conclusion, exposure to atomic bomb radiation affected the occurrence of hyperparathyroidism, suggesting that doses of radiation lower than those used in radiotherapy may also induce this disorder. PMID- 1594766 TI - Dosimetry in photodynamic therapy: oxygen and the critical importance of capillary density. AB - Recently published results of tumor response to various photoradiation protocols in photodynamic therapy appear to contradict accepted definitions of photodynamic dose. In this report, the failure of standard dosimetry models to predict therapeutic outcome is interpreted on the basis of PDT-induced oxygen consumption in tumors with relatively low capillary densities. Calculated estimates of oxygen consumption in photodynamic therapy are combined with the Krogh cylinder model of oxygen diffusion. It is shown that, for tissue volumes in which the intercapillary spacing is less than a specific critical distance, oxygen may be considered constant and unaffected by the therapy. Under these conditions, the 1O2 delivered to a given volume of tissue is spatially uniform and proportional to the number of photons absorbed by the sensitizer. When the intercapillary spacing exceeds the critical distance, the dose of 1O2 varies with radial distance from the capillary wall. In this situation, dose may no longer be considered simply in terms of the product of the photon fluence and the sensitizer absorption coefficient. Since fractionation will increase the 1O2 dose only to cells relatively remote from the capillary wall, the analysis further suggests that fractionating the radiation dose should result in an improved therapeutic ratio for photodynamic therapy. PMID- 1594767 TI - Filter elution assays for DNA damage: practical and mechanistic significance of the DNA in the filter support wash. AB - The alkaline and neutral (or nondenaturing) filter elution assays are popular methods for the measurement of DNA strand breakage and its repair in eukaryotic cells. In both alkaline and neutral elution, it is recommended practice to wash the filter support after removal of the filter and to analyze the DNA recovered by this procedure together with that remaining on the filter as uneluted DNA, although it is not obvious why the DNA in the filter support wash should be so interpreted. We have observed that the sum of the DNA on the filter and that recovered in the filter support wash is approximately constant when the pH of the alkaline filter elution assay for total strand breaks is increased from 12.1 to 12.6, whereas the fraction on the filter itself is markedly smaller at the higher pH. This behavior characterized DNA elution from undamaged cells, as well as from cells treated with various DNA-damaging agents. These findings are consistent with the "tug-of-war" mechanism that has been proposed for alkaline elution, but are inconsistent with the simplest mechanism of the "sieve" class. In the neutral filter elution assay for double-strand breaks, by contrast, the distribution of DNA between the filter and the filter support wash is pH-independent. This suggests that single- and double-stranded DNA segments traverse a filter by different physical mechanisms. Our observations underscore the importance of carrying out the filter support wash and the analysis of the DNA it contains as uneluted DNA in alkaline elution, while indicating that a different analysis of this DNA might be appropriate for neutral elution. PMID- 1594768 TI - Pulsed-field gel electrophoresis in the measurement of DNA double-strand break repair in xrs-6 and CHO cell lines: DNA degradation under some conditions interferes with the assessment of double-strand break rejoining. AB - Pulsed-field gel electrophoresis (PFGE) is a sensitive assay for DNA double strand breaks (DSBs). The application of PFGE to the measurement of DSB rejoining requires attention to conditions after irradiation. When cells are irradiated and incubated while encapsulated in agarose, DNA DSB rejoining appears incomplete or absent due to DNA degradation artifacts. Using PFGE we have measured the DSB rejoining defect in xrs-6 cells and shown how DNA degradation can affect the results. PMID- 1594769 TI - Court orders strikers reinstated to former positions. PMID- 1594770 TI - Failure to timely report test results: cause of stillbirth? Case in point: Clancy v. Euclid General Hospital (584 N.E. 2d 763--OH (1989)). PMID- 1594771 TI - Legal case briefs for nurses. AL.: nursing protocols excluded in death case: reversible error issue; AL.: E.R. nurse toe tags wrong bodies: can nurse rely on police identification? PMID- 1594772 TI - Patient misdiagnosed & invited to "leave": $450,000 verdict. Case in point: Baptist Memorial Hospital v. Bowen (591 So. 2d 74--AL (1991)). PMID- 1594773 TI - An analogical "field" construct in cellular biophysics: history and present status. PMID- 1594774 TI - Historical and contemporary perspectives in vaccine developments: from the vantage of cancer. PMID- 1594775 TI - Role of anti-idiotypic antibodies in induction, regulation, and expression of coxsackievirus-induced myocarditis. PMID- 1594776 TI - [Limitations on the clinical use of pulse oximetry]. PMID- 1594777 TI - [Doctoral theses and memoirs about anesthesia. Documents for a history of Spanish anesthesia]. AB - Based on the importance of document files and first-hand bibliographic sources for studying the history, we have recently investigated the chapter of Doctoral Thesis and Reports on anesthetic topics since we believe that these are fundamental to gain insight into the knowledge of our history. This investigation was planned to find such documents by reviewing the data of several Spanish archives and libraries. We collected 80 works: 14 Reports and 66 Doctoral Theses performed during a period of 95 years (heuristic limits 1847-1942). These papers were classified in several subgroups according to the subjects they deal with: 21 works on inhalation anesthesia, 7 on intravenous general anesthesia, 20 on spinal anesthesia, 10 on locoregional, 7 on anesthesia and metabolism, 12 on obstetric anesthesia, and 3 works on varied anesthesia issues. Analysis of these documents revealed that the authors (physicians and Spanish medical corporations) undertook an accurate consideration of the more relevant scientific subjects at the time of their investigation. We conclude that the works analyzed in the present study represented the beginning of the Spanish investigation on anesthesia. Further investigations may contribute to enrich our historiography. PMID- 1594778 TI - [Selective right bronchial intubation using tracheal tubes under fibroscopic guidance]. AB - We have evaluated the technique of right bronchial intubation for selective right pulmonary ventilation using one lumen tracheal tubes as an alternative to double lumen tubes. We studied 20 patients ASA II-III with a relatively preserved pulmonary function who were programmed for left thoracotomy. We used Shiley nr. 9 or Mallinckrodt nr. 11 tubes. After endotracheal intubation the tube was blindly advanced to the main right bronchus. The position of the tube was assessed by auscultation and it was verified and modified, if necessary, by fibroscopic visualization. The tube was advanced in such a way that Murphy's hole of the endotracheal tube remained in front of the exit of the right superior lobar bronchus. In three patients (15%) blinded placement of the tube was appropriate and in 4 patients (20%) fibroscopic replacement of the tube was required. In the remaining 13 patients (65%) placement of the tracheal tube was considered incorrect: tube rotation in 7 cases, upper placement of the Murphy's hole with respect to the origin of the superior lobar bronchus in 4 cases, and excessive distal placement of Murphy's hole with respect to the superior lobar bronchus in 2 patients. Complications related with the incorrect position of the tube were: leaking of gas into the left bronchium in 5 patients (25%), displacement of the tracheal tube into the main left bronchus requiring withdrawal of the tube to the trachea in one case (5%), hypoxemia (saturation of O2 lower than 90%) in spite of ventilation with FiO2 = 1 in two patients, moderate hypercapnia in three cases, and atelectasis of the right superior lobe during the postoperative phase in three patients (15%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594779 TI - [Utility of the brachial plexus block combined with continuous intradural anesthesia for axillo-femoral bypass surgery]. AB - Extra-anatomic axillofemoral bypass is a surgical procedure that is indicated in cases of occlusive aortoiliac pathology in which the transabdominal way is not feasible or in patients of high risk. We present a preliminary study in which we have prospectively evaluated 14 patients who were received an axillofemoral bypass during 1990. After preoperative evaluation two groups were identified: Group ALR (5 patients) with combined anesthetic blockade of supraclavicular brachial plexus and continuous subarachnoid blockade. Group AG (9 patients) who received balanced general anesthesia. In all cases we obtained a good anesthetic level for surgery. The incidence of complications was similar in both groups. One patient subjected to general anesthesia died. Combined blockade induces a satisfactory analgesia in all surgical interventions without exceeding in any case the maximal doses of anesthetic drugs. Additionally, this technique affords the advantages of regional anesthesia and can be used as an alternative anesthetic procedure in patients of high risk who undergo axillofemoral bypass. PMID- 1594780 TI - [Late postoperative apnea in a premature newborn infant]. AB - We report the case of a premature newborn child (36 weeks) who was operated on a teratoma of the sacrum when he was 12 days old and weighed 2,950 g. The patient presented a late postoperative apnea 17 hours after anesthesia. The anesthetic technique consisted of lumbar epidural blockade with 0.33% bupivacaine at a dose of 2.25 ml and superficial inhalation anesthesia with 0.5% isoflurane. Relaxing muscular agents used in this case were succinylcholine (3 mg) for orotracheal intubation and pancuronium bromide (0.3 mg) for maintaining the anesthetic level. The immediate postoperative phase was uneventful but 17 hours after surgery the patient presented apnea, bradycardia (40 beats/min), and marked cyanosis requiring assisted ventilation with bag and mask during 3 min and initial cardiac massage. Recovery of heart rate was immediate and recovery of ventilation was progressive. The patient was treated with caffeine during one week and no relapses occurred. Pneumocardiographic recordings obtained later on revealed sporadic short lasting episodes of apnea (shorter than 15 s) sometimes associated with bradycardia (40 beats/min lower than baseline). There were no apparent intercurrent or precipitating factors for this apnea. We believe that the present clinical picture corresponds to a late postoperative apnea of unknown origin which required reanimation measures and that until present, there are no reported complications of the anesthetic technique that can explain this episode. PMID- 1594781 TI - [Identification of the epidural space: what to choose?]. PMID- 1594782 TI - [General anesthesia combined with peridural anesthesia in a case of Steinert's disease]. PMID- 1594783 TI - [Obstruction of the left upper lobar bronchus by a double-lumen endotracheal tube. Apropos of a case]. PMID- 1594784 TI - [Multi-organ transplantation of liver and pancreas]. PMID- 1594785 TI - [Why and how to monitor patients in anesthesiology]. PMID- 1594786 TI - [Lack of predictive power of cerebrospinal fluid calcitonin and serotonin concentrations for the intensity of postoperative pain and the duration of analgesia after subarachnoid morphine administration]. AB - Based on the important relationship of calcitonin and serotonin with narcotic drugs at the level of the central nervous system and with the modulating mechanisms of pain sensation, we have studied whether central baseline levels of these modulators possess a predictive value for the assessment of the intensity and duration of narcotic spinal analgesia. Therefore, intradural levels of calcitonin an serotonin were measured in 18 patients who underwent and infraumbilical laparotomy with intradural anesthesia with bupivacaine associated with 0.5 mg of morphine. There was no statistically significant correlation between the levels of calcitonin and serotonin with the age, weight, height, sex, values of analogic visual scale 2, 4, 6, 12 and 24 hours after lumbar punction, and duration of the analgesia. Even though a correlation exists in experimental models, our results indicate that baseline values of modulators calcitonin and serotonin lack of predictive value for the assessment of the degree and duration of narcotic spinal analgesia. PMID- 1594787 TI - [Pressure changes in the pneumoballoon of several endotracheal tubes after the administration of nitrous oxide]. AB - We compare the degree of nitrous oxide diffusion in three types of endotracheal tubes available in the market, by means of continuous monitoring of the pressure attained at the pneumoballoon. Among the systems designed to impede or to minimize nitrous oxide diffusion, we have used in this study the so called "rediffusion system". When the endotracheal tube possesses this system, the pressure attained at the pneumoballoon remained constant throughout the study period (23.2 +/- 0.53 mmHg at time zero vs 24.2 +/- 0.66 mmHg 50 min after administration of protoxide). In contrast, endotracheal tubes without "rediffusion system" showed a statistically significant increase (p less than 0.05) of pneumoballoon pressure (25.2 +/- 2.43 mmHg and 26.7 +/- 1.01 mmHg at time zero vs 45.2 +/- 3.12 and 44.3 +/- 2.41 mmHg 50 min after protoxide administration in the two other types of endotracheal tubes). We believe that during anesthesia with nitrous oxide the pneumoballoon pressure should be monitored or systems that avoid diffusion of this inhalational agent should be inserted. Our results indicate that endotracheal tubes equiped with "rediffusion system" are effective in impeding diffusion of the inhalational agents. PMID- 1594788 TI - [Spinal electrical stimulation. Current indications and results in a series of 46 patients]. AB - We report the clinical results observed in a series of 46 patients with chronic pain who underwent spinal cord electrical stimulation. Candidates were selected according to previous clinical criteria and they were followed-up during a period of 5 to 27 months. Fifteen patients had a residual backache after surgery of the lumbar spine, 19 patients complained angina pectoris, 5 patients peripheral vasculopathies, and 7 subjects had different types of neurogenic pain. A total of 5 patients failed to complete the trial period of 7 to 10 days. Among the 34 patients who continued to use the medullar stimulation, good results were obtained in 75% of cases of backache , 100% of patients with angina and vasculopathies, and 50% of patients with neurogenic pain. There were no relevant complications. We conclude that the results of spinal cord stimulation can be improved by using more strict indications, by performing a previous test period before definitive implantation, and by achieving a large technical experience. PMID- 1594789 TI - [Comparative study of the behavior of isoflurane and halothane in pediatric anesthesia]. AB - This study involves 60 patients below the age of 14 years who were subjected to short duration surgical procedures under inhalation anesthesia with halothane and isoflurane at equivalent CAM in 50% protoxide. The objectives of the study were: a) to establish which of the two inhalational agents produced the more rapid anesthetic induction; b) to determine which exerted the more marked potentiation of the neuromuscular blockade induced by succinylcholine, and c) to compare the anesthetic quality during the induction and recovery periods of both halogenated agents. Induction was more rapid after halothane (mean induction time of 2.91 +/- 0.97 min) than after isoflurane (mean induction time of 6.24 +/- 2.88 min; p less than 0.001). Potentiation of succinylcholine induced neuromuscular blockade was greater after isoflurane than after halothane: the mean time of apnea was 4.56 +/ 1.82 min for isoflurane and 3.41 +/- 1.63 min for halothane (p less than 0.05). Undesirable effects were larger in patients treated with isoflurane than in patients anesthetized with halothane (mean score: 12.60 +/- 3.53 points vs 14.41 +/- 2.33 points; p less than 0.001). The analysis of anesthetic quality during the recovery period gave a mean punctuation of 16.62 +/- 2.21 to patients treated with halothane, whereas patients anesthetized with isoflurane showed a lower score of 14.25 +/- 1.99 points (p less than 0.001). The higher scores corresponded to the most well tolerated anesthetic induction and recovery. The highest attainable score in this study was 18. PMID- 1594790 TI - Dengue-2 virus isolation from humans during an epizootic in southeastern Senegal in November, 1990. PMID- 1594791 TI - The structure and expression of the genome of carlaviruses. PMID- 1594792 TI - The clinical significance of antiviral drug resistance. PMID- 1594793 TI - Management of patients following successful healing of acyclovir-resistant herpes simplex virus infection. PMID- 1594794 TI - On practical aspects of the use of anti-influenza drugs. PMID- 1594795 TI - The clinical significance of drug-resistance mutants of human immunodeficiency virus. PMID- 1594796 TI - HIV1 sensitivity to zidovudine: need for phenotypic analysis. French Antiretroviral Drug Resistance Working Group. PMID- 1594797 TI - Clinical significance of zidovudine-resistant human immunodeficiency viruses. PMID- 1594798 TI - Molecular aspects of AZT resistance in HIV1. PMID- 1594800 TI - Estimating transmission probabilities for chlamydial infection. AB - Estimates of transmission probabilities for sexually transmitted diseases historically come from studies of uninfected individuals exposed to those with a high disease prevalence (for example, prostitutes). However, changes in sexual behaviour, much of which relates to concerns about AIDS, has made identification of populations suitable for such studies extremely difficult. This paper presents a method for estimating these probabilities that utilizes a deterministic model and routinely collected data available in many clinics. Variance estimates for the estimators are also derived. Data for chlamydial infection and sensitivity analyses for the input parameters and assumptions illustrate the method. PMID- 1594799 TI - Human conglutinin-like protein inhibits infection by the human immunodeficiency virus-1 in vitro. PMID- 1594801 TI - Analysis of the incubation period for measles in the epidemic in Greenland in 1951 using a variance components model. AB - This paper presents a model for analysing the incubation period of highly infectious diseases in populations where almost all susceptibles become infected during an epidemic. The model leads to a simple method for estimating the variance of the duration of the incubation period without any distributional assumptions. Further, the influence of covariates on the duration of the incubation period can be analysed. Data from the epidemic of measles in Greenland in 1951 are analysed and it is found that intersymptom times are correlated within households, suggesting that secondary cases are infected almost simultaneously. This result is inconsistent with a variation in the times of infection of secondary cases within a household which is often assumed when analysing data on measles. Prophylactic treatment did not prevent infection in the epidemic in Greenland, but it is found that the incubation period tended to be shorter for persons not receiving prophylactic treatment. PMID- 1594802 TI - Effects of different parametric estimates of seroconversion time on analysis of progression to AIDS among Italian HIV-positive haemophiliacs. AB - The purpose of this study was to estimate seroconversion time using different parametric methods and to assess their influence on the estimation of the incubation time between HIV infection and onset of AIDS. Study subjects were 712 HIV-positive haemophiliacs enrolled in the Italian National Registry of patients with congenital coagulation disorders. Seroconversion time was estimated using the mid-point of each seroconversion interval (MID), the median of each interval under an estimated uniform distribution with cutpoints at December 1981 and December 1985 (MUU), the median of each interval under an estimated Weibull distribution (MUW), and the median of three random values drawn from each interval under the Weibull distribution (RUW). Kaplan-Meier survival analysis showed that the cumulative incidence of AIDS over a 7-year period was 11.6 per cent (SE 1.3 per cent) when using the MID estimate of seroconversion time, 10.8 per cent (1.2 per cent) with the MUU estimate, and 13.4 per cent (1.3 per cent) and 12.3 per cent (1.3 per cent) when using MUW and RUW estimates, respectively. This study demonstrates that the estimate of seroconversion time does not seem to be a major factor affecting estimates of AIDS incidence since the different techniques for estimating HIV seroconversion time yielded very similar results. PMID- 1594803 TI - Adjustments to the Mantel-Haenszel test for data from stratified multistage surveys. AB - The usual form of the Mantel-Haenszel test statistic assumes independent observations. This is inappropriate for data from a stratified multistage survey. Two alternative adjustments to the test statistic are developed to deal with this: (a) a modification of the effective sample size for each row of each table, using the design effects, extending a method proposed by Donald and Donner for familial aggregation studies; (b) a Taylor series approximation to the variance of the square root of the numerator of the Mantel-Haenszel statistic. Both methods are evaluated by application to both simulated and real data. The two methods perform equally well, and offer a considerable improvement over the unadjusted test statistic when observations from the same cluster are highly correlated. A simplified adjustment is also considered, as is the need for correction to the variance of the odds ratio estimator. PMID- 1594804 TI - A note on the presentation of matched case-control data. AB - Many matched case-control studies present tables of pooled data ignoring matching. The value of such tables is questioned. If tables of data are included they should certainly not lead to misleading results. Tables that yield consistent estimates in matched studies are considered. PMID- 1594805 TI - Application of empirical Bayes inference to estimation of rate of change in the presence of informative right censoring. AB - We apply parametric empirical Bayes inference of Morris to the estimation of rate of change from incomplete longitudinal studies where the right censoring process is considered informative, that is, the length of time the subjects participate in the study is associated with level of the study variable. Ignoring such an association can result in a biased estimate of rate of change. The proposed method provides estimates of rate of change for individual subjects as well as for the entire group, adjusted for informative right censoring. The method is considered more robust than those based on a specific parametric model for the censoring distribution. Under non-informative right censoring these estimators of slopes are equivalent to the Bayes estimators derived by Fearn. We illustrate the method with an example involving renal transplant data. We evaluate the method's performance through a simulation study. PMID- 1594806 TI - Sample size requirement for repeated measurements in continuous data. AB - In this paper we extend Bloch's discussion on the usefulness and the limitations in the application of repeated measurements per subject in study designs. We derive general sample size formulae for any finite number of comparison groups to calculate the required number of subjects with repeated measurements, that do not have to be conditionally independent. For fixed total cost, we discuss the optimal sample allocation for repeated measurements needed to maximize the power and the underestimation when using Bloch's sample size formula if in the hypothesis testing procedure the variance parameters are unknown. We have also included a quantitative investigation of the effectiveness of taking repeated measurements per subjects to reduced the required number of subjects for a given power at a given alpha-level. PMID- 1594807 TI - Closed-form estimates for missing counts in two-way contingency tables. AB - One method for analyzing contingency tables with missing observations is to model the missing-data mechanism using log-linear models. Previous methods for obtaining estimates (of missing counts and parameters) have required an iterative algorithm. In many cases, however, one can obtain estimates by use of a simple algebraic formula. We illustrate the method with data on smoking and birth weight. PMID- 1594808 TI - Monitoring clinical trials with a conditional probability stopping rule. AB - Conditional probability procedures offer a flexible means of performing sequential analysis of clinical trials. Since these procedures are not based on repeated significance test, the number and schedule of the interim analyses is less important than with group sequential procedures. Their main disadvantage is that the magnitude of their effect on the significance level is difficult to assess. This paper describes a conditional probability procedure which attempts to maintain the overall significance level by balancing the probabilities of false early rejection and false early acceptance. Monte Carlo sampling results suggest that this procedure can achieve a large reduction in expected sample size without greatly affecting either the significance level or power of the trial. PMID- 1594809 TI - A decision-theoretic evaluation of early stopping rules. AB - We consider the decision-theoretic evaluation of early stopping rules for clinical trials. We describe a hypothetical phase III, two-arm trial with interim analysis, modelling it as a decision problem. We present methods for constructing a group-sequential test that is optimal for a given utility and prior distribution, and for determining a utility and prior under which a given test is optimal. Using our methods, we construct optimal tests for utilities and priors representing a variety of perspectives: a view that seeks to maximize the long run response rate, a view that seeks to maximize the chance of a correct decision, and a personal view elicited from a medical oncologist. Characteristics of the optimal rules are sensitive to the input utilities and priors, and their critical values and sampling properties can differ markedly from those of group sequential tests. We also compute utility functions and priors under which some standard group-sequential stopping rules are optimal. Our results suggest that the group-sequential tests, considered as decision procedures, imply a symmetry in the decision problem that is inconsistent with the response-rate perspective. We conclude that decision theory is a useful device for illuminating the sometimes conflicting goals of clinical research, and that the use of decision theory in designing clinical trials could lead to marked changes in statistical criteria for early termination. PMID- 1594810 TI - On identifying a positive dose-response surface for combination agents. AB - This article concerns construction of a confidence surface for tangential slopes of the dose-response surface of a combination therapy to identify where response increases as a function of drug dosage. This approach extends to the assessment of the effectiveness of the combination therapy. PMID- 1594811 TI - Is the 'simple carry-over' model useful? AB - It is argued that the models usually employed for carry-over effects in cross over trials are not reasonable. The example of a non-linear dose response for a dose-finding trial arranged in a Williams square is developed to show that if carry-over is present to any appreciable degree the usual statistical models provide no guaranteed protection against its effects. It is concluded that the most reasonably defended assumption about carry-over effects is that no important carry-over has taken place and that, where this assumption cannot be defended, statistical models provide no satisfactory substitute for it. PMID- 1594812 TI - Regression toward the mean in 2 x 2 crossover designs with baseline measurements. AB - Clinical trials often involve the study of patients whose values for some quantitative characteristic are in the extreme of the distribution for the normal population. Subsequent observation of the characteristic of interest will ordinarily tend to regress toward the mean of the distribution even in the absence of a treatment effect. We consider the impact of regression toward the mean in the analysis of data arising in 2 x 2 crossover trials with two baseline measurements. The usual summary statistics can be especially misleading in the presence of regression toward the mean. PMID- 1594813 TI - Sample size requirements for stratified cluster randomization designs. AB - Sample size requirements are provided for designs of studies in which clusters are randomized within each of several strata, where cluster size itself may be a stratifying factor. The approach generalizes a formula derived by Woolson et al., which provides sample size requirements for the Cochran-Mantel-Haenszel statistic. Issues of data analysis are also discussed. PMID- 1594814 TI - Estimating the number of clusters for the analysis of correlated binary response variables from unbalanced data. AB - Dominating the literature on sample size determination are papers concerned with observations collected from independent responses. We discuss in this paper, under the common correlation model for binary responses, the issue of estimating the number of groups when the sampling units are clusters of variable sizes. PMID- 1594815 TI - Clustering in sparse data and an analysis of rhabdomyosarcoma incidence. AB - Time series of epidemiologic events often contain periods of atypically low or high frequency. Correspondingly, for quite rate diseases there occur instances of long vacuous durations interrupted noticeably by periods of some disease activity. A recent community-based observation of the incidence of rhabdomyosarcoma (RMS), and an investigation of it, yielded sparse data of this general description. We introduce a combinatorial test for patchy time series and apply it to the RMS data. We comment on the prevalent practice of post hoc data analysis of alleged clusters, and on scale effects. PMID- 1594816 TI - Designs and analysis of two-stage studies. AB - This paper concerns the design and analysis of two-stage studies, where, at the first stage, the response and the exposure variables are available among a large group of subjects. The other covariables, however, are available in only a subset of the large group, obtained in a second-stage sample. This paper introduces a class of twelve such two-stage designs, including two-stage case-control and case cohort designs as special cases. In analysing such two-stage data, one objective is to extract information about the relationship between the exposure variable and the response after controlling for other covariables. We discuss three statistical methods to analyse the data and report results of Monte Carlo stimulation to study the efficiency of the three methods. PMID- 1594817 TI - Analysing the relationship between change in a risk factor and risk of disease. AB - There are numerous examples in the epidemiologic literature of analyses that relate the change in a risk factor, such as serum cholesterol, to the risk of an adverse outcome, such as heart disease. Many of these analyses fit some type of regression model (such as logistic regression or the Cox model for survival time data) that includes both the change in the risk factor and the baseline value as covariates. We show that this method of adjusting for the baseline level can produce misleading results. The problem occurs when the true value of the risk factor relates to the outcome, and the measured value differs from the true value due to measurement error. We may find the observed change in the risk factor significantly related to the outcome when there is in fact no relationship between the true change and the outcome. If the question of interest is whether a person who lowers his level of the risk factor by means of drugs or lifestyle changes will thereby reduce his risk of disease, then we should consider an association due solely to measurement error as spurious. We present a method that adjusts for the measurement error in a linear regression analysis and show that an analogous adjustment applies asymptotically to logistic regression. As in other errors-in-variables problems, this analysis depends on knowledge of the relative variances of the random variation, the true baseline value, and the true change. Since the magnitudes of these variances are usually unknown and sometimes unknowable (the distinction between true change and measurement error being ambiguous), we recommend a sensitivity analysis that examines how the analysis results depend on the assumptions concerning the variances. The commonly used analysis method corresponds to the extreme case in which there is no measurement error. We use data from the Framingham Study and simulations to illustrate these points. PMID- 1594818 TI - Pre-natal blood lead levels and learning difficulties in children: an analysis of non-randomly missing categorical data. AB - This paper presents an analysis of categorical variables subject to non-response. We incorporate the incomplete data into the analysis by modelling the distribution of the variables of interest and the non-response mechanism. We discuss issues of model selection and interpretation and the effect of discarding incomplete observations. In addition, we describe how to perform all of the computations with standard statistical software. We discuss the problem of incomplete categorical data within the context of a study of the effect of lead exposure on learning difficulties in children. In this study, many of the children are not observed on some of the variables of interest. It is particularly important in this study to incorporate the incomplete data, since there is evidence that non-response is related to the variables of interest. We reach different conclusions when we incorporate the incomplete data into the analysis than we reach when we discard the incomplete data. We also examine the sensitivity of our conclusions to the choice of a model for the non-response mechanism. PMID- 1594819 TI - Applications of crude incidence curves. AB - Crude incidence curves display the cumulative number of failures of interest as a function of time. With competing causes of failure, they are distinct from cause specific incidence curves that treat secondary types of failures as censored observations. After briefly reviewing their definition and estimation, we present five applications of crude incidence curves to show their utility in a broad range of studies. In some of these applications it is helpful to model survival time distributions with use of two different time metameters, for example, time from diagnosis and age of the patient. We describe how one can incorporate published vital statistics into the models when secondary types of failure correspond to common causes of death. PMID- 1594820 TI - Estimating the stage-specific numbers of HIV infection using a Markov model and back-calculation. AB - The back-calculation method has been used to estimate the number of HIV infections from AIDS incidence data in a particular population. We present an extension of back calculation that provides estimates of the numbers of HIV infectives in different stages of infection. We model the staging process with a time-dependent Markov process that partitions the HIV infectious period into the following progressive stages and/or substages: stage 1, infected but antibody negative; substages 2-3; antibody positive but asymptomatic; substages 4-6, pre AIDS symptoms and/or abnormal haematologic indicator, stage 7, clinical AIDS. We also model an eight stage, decreased due to AIDS. The model allows for time dependent treatment effects that slow the rate of progression in substages 4-7. We use the estimated AIDS incubation period distribution for the Markov model in back calculation from AIDS incidence data to estimate the total number of HIV infections and the parameters of the infection probability distribution. We then use these estimates in the Markov model to estimate the stage-specific numbers of HIV infections over the course of the epidemic in the population under study. Example calculations employ data for epidemic in San Francisco City, Clinic Cohort. PMID- 1594821 TI - A comparison of two simple hazard ratio estimators based on the logrank test. PMID- 1594822 TI - [Recurrent spontaneous miscarriage]. AB - Spontaneous recurrent miscarriages still represent a poorly defined entity. It is commonly accepted that they include early (1st trimester) spontaneous abortion thus excluding those related to well documented chromosomal, anatomical, hormonal or autoimmune causes such as SLE or anticardiolipin syndrome. There is also a general consensus based upon historical series to require at least three consecutive miscarriages. In a series of 58 consecutive couples with recurrent miscarriages studied at the clinics of immunology of pregnancy, a careful investigation could demonstrate the high incidence of anatomical abnormalities detected by hysterosalpingography and consisting mostly of uterus bicornis or uterus septus. This finding emphasises the importance of this examination. Some of these cases required surgical or endoscopic therapy. Only one patient displayed chromosome abnormalities excluding her from the definition of spontaneous recurrent miscarriage. The other patients were treated either with paternal leucocytes or gammaglobulins. PMID- 1594823 TI - [Anti-phospholipid antibodies and recurrent miscarriage]. AB - Antiphospholipid antibodies are associated with arterial and venous thromboembolism, thrombocytopenia and fetal loss. According to several studies the obstetrical problems associated with antiphospholipid antibodies can be successfully treated with immunosuppressive or anticoagulant drugs. The detection of these antibodies is difficult owing to the lack of standardization and of specificity of the laboratory tests. PMID- 1594824 TI - [Alloimmune neonatal thrombocytopenia]. AB - Neonatal alloimmune thrombocytopenia (NAIT) is due to fetomaternal incompatibility for platelet specific antigens, most frequently HPA-1a (PLA1) and HPA-5b (BRa). It occurs in approximately 1/2.000-1/5.000 births. The most serious complication of NAIT is intracranial hemorrhage. The risk of life-threatening hemorrhage must lead to prompt diagnosis and effective therapy. Improvements in antenatal diagnosis and in utero therapy facilitate appropriate management of pregnancy at risk for NAIT. We report our experience with the serological diagnosis of 14 NAIT cases using new performing techniques such as western blotting (WB) and MAIPA (monoclonal antibody specific immobilization of platelet antigens). PMID- 1594825 TI - [Fetomaternal alloimmunization: role of cordocentesis]. AB - Twenty one pregnancies complicated by alloimmunization were managed by the use of intravascular method on an outpatient basis. One group was made of 9 women having had at least one pregnancy with a severely affected fetus. The other group was composed of 12 women without a previously affected infant; in 5 cases a situation at risk, either a transfusion (4 cases) or a severe obstetrical hemorrhage (1 case), was evidenced. Knowledge of fetal blood type (2 cases) and hematocrit determination obtained by fetal blood sampling allowed treatment individualized to the specific needs of each patient. In total 59 cordocenteses were performed, including 19 intrauterine transfusions. PMID- 1594826 TI - [Headache, fever and behavior problems. Lymphoma]. PMID- 1594827 TI - [Immunology of pregnancy]. AB - The fetus expresses paternally inherited gene products and tissue-specific differentiation antigens. Hence, it can be considered as a semi-allogeneic graft towards which the maternal immune response is characterized by tolerance instead of rejection. As such, the pregnancy represents a challenge to the laws of transplantation. For the immunologist, the question is not why some women miscarry, but rather, why most women do not miscarry? A bulwark of proscriptive or inhibitory influences must be built to ensure an absence of anti-fetal reactivity. The mechanisms underlying the induction of tolerance are poorly understood. Failure to obtain an adequate maternal immune response might be responsible for some forms of miscarriages, especially recurrent spontaneous abortions. Increased knowledge of those mechanisms could have implications in various fields, such as infertility, transplantation and oncology. PMID- 1594828 TI - [Stripping and surgical exeresis of varicose veins]. PMID- 1594829 TI - [Ambulatory phlebectomy at the doctor's office]. PMID- 1594830 TI - [Cryosurgery of varicose veins]. PMID- 1594831 TI - [Anesthesia in surgery of varicose veins]. PMID- 1594833 TI - [Conservative hemodynamic ambulatory treatment of venous insufficiency]. PMID- 1594832 TI - [A decisive item in the evolution of the health care system: ambulatory surgery of varicose veins]. PMID- 1594834 TI - [Medical care in the surgical treatment of varices]. PMID- 1594835 TI - [Accompanying patients with spinal cord injuries in their work of grief]. PMID- 1594837 TI - [Surgery of varicose veins]. PMID- 1594836 TI - [Inservice training and evaluation in a thoracic surgical intensive care service]. PMID- 1594839 TI - [Proctological surgery (2). Hemorrhoids, anal fissures]. PMID- 1594838 TI - [A more hemodynamic surgery...]. PMID- 1594840 TI - [Blood derivatives]. PMID- 1594841 TI - [Etiology and epidemiology of varicose veins]. PMID- 1594842 TI - [Contributions of Doppler ultrasonics and echography to the pathology of the superficial veins]. PMID- 1594843 TI - [Clinical aspects of arrhythmias]. AB - Arrhythmias are frequent and occur in normal individuals as well as in patients with structural heart disease. In supraventricular arrhythmias the indication for treatment is mainly based on symptoms. In atrial fibrillation the thromboembolic risk has to be taken into account. In ventricular arrhythmias, especially in combination with significant structural heart disease, prognostic considerations play an important role in decision-making. PMID- 1594844 TI - [Electrophysiology: indications for and results in programmed stimulation]. AB - Since the early seventies electrophysiology is a diagnostic tool to evaluate mechanisms of arrhythmias and to control drug therapy. Advances in technology have led to newer methods, such as radiofrequency ablation and the use of implantable defibrillators. These techniques as well as their diagnostic, prognostic and therapeutic indications will be discussed. PMID- 1594845 TI - [Drug therapy in supraventricular arrhythmia]. AB - In view of their potentially dangerous proarrhythmic effects, antiarrhythmic drugs should only be prescribed for patients with poorly tolerated symptomatic supraventricular arrhythmias. The choice of a suitable preparation depends not only on the type of arrhythmia, but also on the underlying heart disease and left ventricular function. Digoxin, verapamil, sotalol and quinidine remain first-line drugs, while in view of recent trials the type-1c antiarrhythmics (flecainide) should only be given in cases resistant to other agents. Amiodarone is also an important and efficacious "reserve" antiarrhythmic, which has to be utilized at low doses to avoid its well-known side effects. PMID- 1594847 TI - [Hip diseases in children]. AB - In the orthopedic practice, the hip joint is of special importance at all ages. For the general practitioner and the pediatrician are those disorders of the hip of high importance, for which early diagnosis and initiation of treatment is critical for prognosis. The following disorders should be looked for in priority, if symptoms indicate a possible affection of hip: congenital dysplasia and dislocation of the hip, coxitis, slipped capital femoral epiphysis, and tumors. One should always be aware that especially in children disease of the hip need not necessarily present with symptoms directly located within the region of the hip. Especially the child often complains only about knee or vague leg pain, while having a disorder of the hip; therefore, the cause of any pain should always also be looked for proximal to the structure, where the pain may be localized by the patient. PMID- 1594846 TI - [Pediatric emergencies]. AB - We describe the most frequent emergencies in pediatrics and discuss their differential diagnosis and therapy. Dyspnea, shock, coma, convulsions, infectious CNS affections, head injury and burns are reported in detail. The importance of correct diagnosis and correct clinical assessment is emphasized, as they influence therapy and further management of the patients. PMID- 1594848 TI - [Health and disease in leisure-time families]. AB - This paper is concerned with the actual anthropological background of medical practice. Cultural differentiation and specialisation have led to a splitting of all areas of living in multiple ways. This process of fission is pathogenic when areas belonging together are not lived together respectively are not diagnosed and treated together or when single aspects are neglected seriously. The common recognition of separated areas as "dual entities" requires an adapted perception and a communicating, complementary approach to medical questions. PMID- 1594850 TI - [What is your diagnosis? Compression neuropathy of the genitofemoral nerve]. PMID- 1594849 TI - [Obesity. Various aspects in daily practice]. AB - Overweight and obesity are the most often encountered disease conditions in general practice. Recent evidence of the importance of fat distribution is discussed. The basic therapeutic approach for the most effective therapy of obesity is probably the combination of a dietary (hypocaloric), a behavioral and a physical activity approach. In this general overview the physiologic background of abdominal obesity and some selected therapeutic implications are discussed. PMID- 1594851 TI - [Gallstone ileus--still a current disease]. AB - Two cases of gall-stone ileus during the past months have encouraged us to discuss the epidemiology, pathogenesis, diagnosis and therapy. This pathology is not as rare as one thinks and represents 23% of cases of mechanical ileus of the small intestine in patients over 65 years of age, thus being the third cause after stenosis due to carcinoma and incarcerated hernia. The importance of this illness is due to two factors: the diagnostic difficulties because of a periodic symptomatology with often a lack of typical radiologic signs and the still important mortality of 5 to 10% today. We present the casuistic of seven cases which have occurred over the last 15 years in our hospital and compare our experience with those of the literature. We discuss the therapeutic problem of enterolithotomy or one-stage repair. The main point for a reduction in mortality is an early diagnosis with the consequent reduction of the time from the appearance of the ileus to the operation. PMID- 1594852 TI - [Transverse myelitis and optic neuromyelitis in children. Apropos of 3 case reports]. AB - We report on three children with acute transverse myelitis. One of them also had optic neuritis. In connection with these three cases, we discuss etiology, diagnosis and outcome of transverse myelitis in childhood and possible involvement of the optic nerve. Our observations show the variability of spinal cord deficit and the fact that there can be a good prognosis, despite severe initial neurological deficits and massive elevation of basic myelin protein in children with ATM. PMID- 1594853 TI - [Retroperitoneal rectum perforation during barium enema]. AB - The examination of rectum and colon with barium sulfate is a method which is increasingly replaced by the endoscopy; therefore, the routine of doing this examination is increasingly vanishing. This means that the risk of this method increases. We report a case and discuss the symptomatology as well as the management of a perforation of the rectum during an examination with barium sulfate. PMID- 1594854 TI - [A case from practice (243). Reactive arthritis following gastrointestinal infection]. PMID- 1594855 TI - [The critical concept of perversion]. PMID- 1594856 TI - [Perverse interactions]. PMID- 1594857 TI - [Perversions in 1991]. PMID- 1594858 TI - [Exhibitionism: from act to discourse]. PMID- 1594859 TI - [Treatment of perversion in the sex clinic of Hamburg]. PMID- 1594860 TI - [The character of perversion in marriage counseling]. PMID- 1594861 TI - [Sex deviations: aspects of couples' dynamics]. PMID- 1594862 TI - [Prison and perversion]. PMID- 1594863 TI - [Epidemiology of pneumonias diagnosed in an ambulatory practice]. PMID- 1594864 TI - [Comparative study of ambulatory clients in private and public psychiatry]. PMID- 1594865 TI - [Moratorium on silicone breast implants]. PMID- 1594866 TI - [Complement deficiency and lupus erythematosus]. PMID- 1594867 TI - [Centenary of the Medical Association of the Canton Geneva (1892-1992)]. PMID- 1594868 TI - [The physician facing health cost increase]. PMID- 1594869 TI - [Hyper- and hypocalcemia: diagnosis and treatment]. AB - The establishment of an abnormal calcemia first requires confirmation by a second measurement that should then be interpreted in relation to albuminemia. Should the abnormality be confirmed, measurement of intact parathormone in serum can help distinguishing between a parathyroid or non parathyroid source of origin. In presence of plasma calcium level lower than or equal to 2.9 mmol/L regular monitoring should be provided and aggravating factors such as thiazide diuretics, dehydration or high calcium intake, avoided. If plasma calcium is greater than 3 mmol/L the patient should first be rehydrated. In case of primary hyperparathyroidism, parathyroidectomy is the only effective treatment. In neoplastic hypercalcemia bisphosphonates are the first choice treatment when antitumoral therapy turns out to be insufficient. Hypocalcemia can be effectively corrected by calcium and vitamin D derivatives. PMID- 1594870 TI - Is erythromycin indicated in pregnancy? PMID- 1594871 TI - Time to stop the debate. PMID- 1594872 TI - New insurance covers HIV exposure. PMID- 1594873 TI - Temporary pacemakers. PMID- 1594874 TI - Electrical support for the heart. Rate-responsive pacers. PMID- 1594875 TI - Cancer pain: which drugs for which patient? PMID- 1594876 TI - A new delivery system makes pain control easier. PMID- 1594877 TI - Only nurses know. PMID- 1594878 TI - Take the EKG one step further. PMID- 1594879 TI - Cranial nerve assessment. PMID- 1594880 TI - Your work is lasting. PMID- 1594881 TI - An ally who'll alert you to danger. PMID- 1594882 TI - Pasta: the perfect pick-me-up? PMID- 1594883 TI - Maggots took charge of this homeless patient's hygiene. PMID- 1594884 TI - Metabolism of the aminoterminal propeptide of type III procollagen in cultures of human proximal tubular cells. AB - Degradation of the intact form of the aminoterminal propeptide of type III procollagen (PIIINP) has been established in the liver, whereas the col 1 domain of PIIINP is extracted by the kidneys. We used native human PIIINP and col 1 domain of PIIINP to investigate the degradation of PIIINP in cultures of human proximal tubular cells. Normal renal tissue was obtained from the healthy part of kidneys surgically removed and from biopsies from a total of 10 patients. The degradation was characterized by incubation of [125I]-PIIINP followed by gel filtration. We found that in physiological concentrations (4.4 micrograms l-1 and 11.9 micrograms l-1 intact PIIINP was almost totally degraded, but not col 1 domain. High concentrations of PIIINP (20-50 micrograms l-1) had a non-linear, non-monoexponential degradation over time, which suggests several steps. Gel filtration of [125I]-PIIINP after 1 h, 3 h, 6 h and 24 h of incubation confirmed the observation by showing the rapid formation of a high-molecular-weight fraction, followed by the slower formation of a low-molecular-weight fraction. The high-molecular-weight fraction was PIIINP immunoreactive, but not the low molecular-weight fraction. We conclude that cultures of human proximal tubular cells degrade intact human PIIINP by the formation of high- and low-molecular weight fractions. Earlier findings that extraction of the PIIINP col 1 domain takes place in the kidneys, cannot be explained by degradation by the proximal tubular cells. PMID- 1594885 TI - Characterization of cellular and elevated serum phospholipase A2 activities with a comparison of two methods. AB - The phospholipase A assay of Hoffmann et al based on the enzymatic photometric determination of the fatty acids liberated from soy-bean phospholipids was compared with the fluorometric assay of Thuren et al. where a synthetic pyrene labelled substrate is used. Sera from patients with suspected pancreatitis or sepsis were studied. High values compared well while the Hoffmann method was not sensitive enough to detect slightly elevated values in sera from patients with suspected pancreatitis. The phospholipase A2 activities from enzymes purified from human duodenal juice, human sera from patients with sepsis and rat liver mitochondria were characterized in regard to activity towards several synthetic pyrene-labelled substrates, activation by Ca2+ and inhibition by Sr2+ and Mg2+. The enzyme from serum was distinctly different from both the pancreatic secretory and the mitochondrial ones, both in its substrate specificity pattern and in being most strongly inhibited by Mg2+. PMID- 1594886 TI - Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter. AB - Iopentol (mean dose 0.42 g I kg-1) was administered for abdominal aortography and pelvic angiography in 10 patients with advanced non-diabetic chronic renal failure (S-creatinine 672 +/- 259 mumol l-1, mean +/- SD). Renal glomerular function measured as creatinine clearance and plasma clearance of [99Tcm]-diethyl enetriaminepentaacetic acid (DTPA) was unchanged by iopentol, as also was urinary excretion of the renal tubular enzymes N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP). The elimination of iopentol from serum and urine was delayed, and detectable serum and urine concentrations were found 5 days after administration of the contrast medium. Creatine clearance was 47% higher than the corresponding renal iopentol clearance. Plasma iopentol clearance, measured as the total area under the plasma concentration curve, was 40% higher than renal iopentol clearance because of extrarenal elimination of iopentol. We conclude that abdominal aortography with iopentol can be performed without effects on renal glomerular or tubular function parameters in patients with advanced renal failure. If iopentol is used for measurement of glomerular filtration rate (GFR) in this group of patients, one should measure renal clearance, as plasma clearance overestimates GFR. PMID- 1594887 TI - Preanalytical factors and standardized specimen collection: influence of psychological stress. AB - In order to devise and evaluate standardized specimen collection procedures, we studied the influence of psychological stress on the results of commonly analysed blood components: creatine kinase, lactate dehydrogenase, total protein and albumin in serum and blood picture. In addition, serum cortisol was assayed. Two kinds of stress were used: the Stroop test, a colour conflict task, and the thrill caused by the first jump of new parachutists. More changes were observed after the parachutist test than after the Stroop test. There was a difference in the responses of males and females. Females were more sensitive, especially to the parachutist test. Most of the changes observed were interpreted as being caused by haemoconcentration, possibly related to muscular tension. Cortisol, commonly used to indicate the level of stress, did not react much and is therefore not a good index of psychological stress. PMID- 1594888 TI - Co-variation of alanine aminotransferase levels with relative weight in blood donors. AB - The association between alanine aminotransferase (ALAT) and body mass, sex and age was examined in 6036 consecutively tested blood donors. ALAT, age and body mass were higher in male donors than in female donros. The non-normal ALAT distribution curve normalized after 1n transformation, which made statistical analysis of the data more feasible. Multiple regression analysis demonstrated that ALAT was influenced by sex and relative weight, in that order, and very poorly by age. It is concluded that obesity is a major cause of raised ALAT in this predominantly healthy donor population. PMID- 1594890 TI - Enzymatic cleavage of guanosine triphosphate (GTP) by GTP cyclohydrolase I. PMID- 1594889 TI - Angiotensinogen in chronic liver disease. AB - The renin substrate angiotensinogen (AGT) belongs to a supergene family of proteins that also includes alpha 1-antitrypsin (AAT) and alpha 1 antichymotrypsin (ACT), acute-phase reactants with known serine proteinase inhibitory (serpin) function. AGT lacks a known inhibitory function but is an acute-phase reactant. In this study we have compared the plasma levels, as analysed by electroimmunoassay, of AGT with AAT in patients with different types of chronic liver disease. AAT levels are regularly elevated in liver disease patients in contrast to AGT, which remains normal until late in the disease course. The AGT levels (mean +/- SD) were: in alcoholic cirrhosis (n = 19) 100 +/ 27.3%, in chronic active hepatitis (n = 14) 100 +/- 23.2%, in primary biliary cirrhosis (n = 18) 106 +/- 26.1% and in non-alcoholic cirrhosis (n = 15) 92 +/- 38.4%. Only occasionally were levels less than 50% of normal seen. In general, AGT levels were unrelated to sex and type of underlying liver disease and did not correlate with degree of hepatocellular impairment. Crossed immunoelectrophoresis showed no abnormal charge heterogeneity of AGT in patients with low levels. Our data are consistent with a dissociate expression of the homologous serpin genes in chronic liver disease. We speculate that the magnitude of the dissociated response is influenced by hormonal factors. PMID- 1594891 TI - Free plasma catecholamine levels in healthy subjects: a basal and dynamic study. The influence of age. AB - We studied the levels of free plasma noradrenaline (norepinephrine, NE), adrenaline (epinephrine, E), and dopamine (DA) in 143 normal subjects, either basally or, in a part of them, in response to four tests stimulating the sympathoadrenomedullary activity: the tilt-table test (TTT), the cold-pressor test (CPT), the mental-arithmetic test (MAT), and the insulin tolerance test (ITT). In both cases we evaluated the influence of age, which is considered the main physiological variable affecting the peripheral sympathetic activity. A normal distribution of values was observed, in the basal study, only for NE, while E and particularly, DA levels were distributed in an non-homogeneous fashion; a direct correlation was observed between age of subjects and NE levels, while neither E, nor DA levels showed any correlation with the aging process; sex did not influence any of the catecholamines. In the dynamic study, CPT, ITT and, above all, TTT elicited a significant rise in NE levels, while the E release was greatly stimulated by the insulin-induced hypoglycaemia. Neither NE, nor E levels rose after the MAT stimulation. Also in this case, the elderly showed an increased noradrenergic responsiveness when compared with the young subjects, confirming the existence of an 'up-regulation' of the peripheral sympathetic tone in old people. PMID- 1594892 TI - Hemispheric differences in the perception of words and faces in deaf and hearing children. AB - The purpose of this study was to investigate hemispheric functional asymmetry in 18 normal hearing children and 18 congenitally deaf children aged 13-14 years. The task was identification of a visual stimulus (3-letter word or photograph of a face) presented in either the left or right visual field. The children responded by pointing to the target stimulus on a response card which contained four different words or three different faces. The percentage of errors for presentations to the two visual fields were analysed to determine hemispheric dominance. The pattern of hemispheric differences for the hearing children was consistent with that from previous investigations. The results for the deaf children differed from those of the normals. In word perception we observed a right hemisphere advantage and in the face recognition a lack of hemispheric differences. These results point to a lack of auditory experiences which is affecting the functional organization of the two hemispheres. It is suggested that the necessity to make use of visuo-spatial information in the process of communication causes right hemisphere dominance in verbal tasks. This may influence the perception of other visuo-spatial stimuli which may yield a lack of hemispheric asymmetry in face recognition. PMID- 1594893 TI - Mechanisms of long-term dark adaptation. AB - It has previously been suggested that long-term dark adaptation is controlled by bleaching signals that regulate the activity of an allosteric, positively cooperative protein (Stabell et al., 1986a, b). Recent biochemical evidence strongly supports this assumption, indicating that the primary regulator of the light-sensitive channels in the plasma membrane of the outer segments of the photoreceptors is a homo-oligomeric, allosteric, positively cooperative protein. In this report, we discuss the possibility that signals from bleached photopigments may control the dark-adaptation process through the allosteric protein of the plasma membrane. It is suggested that the concentrations of the bleached photopigment and of the allosteric effector are reciprocal quantities. PMID- 1594894 TI - Maternal adjustment during pregnancy and the infant's first year. AB - The study aimed at establishing the predictive validity of clinical observations and interview data collected during late pregnancy. 40 pregnant women from a Swedish non-risk population were interviewed about psychological and somatic well being, significant relationships and delivery expectations. Pregnancy adjustment was also assessed by the maternal health clinic midwife. After the birth of the child, the mothers were interviewed in the delivery hospital and during home visits when the infants were 2 and 6 weeks, and 4, 8 and 12 months old. The results showed that pregnancy adjustment, as assessed by the mothers themselves, acted as a significant predictor of the early maternal adjustment and the adjustment towards the end of the infant's first year. The midwives' assessments significantly predicted maternal adjustment towards the end of the first year. Pregnancy data did not correlate with maternal delivery experiences. PMID- 1594895 TI - The impact of consonant clusters on preschool children's phonemic awareness: a comparison between readers and nonreaders. AB - Preschool children's ability to segment and blend real words and nonsense words, with and without consonant clusters was investigated in two experiments. In the first experiment, preschool children's ability to segment real words into phonemes was examined. Readers performed better than nonreaders on a phoneme counting task and words containing consonant clusters were harder to segment compared to words without consonant clusters. In experiment two, the ability to segment and blend nonsense words was investigated. Nonreaders had significantly more difficulty with nonsense words compared to readers in both a phoneme synthesis and a phoneme analysis task. A two-way interaction between reading level and word type showed that nonsense words containing consonant clusters were particularly difficult for nonreaders. The results were discussed in relation to theories suggesting that syllables consist of an onset and a rime. PMID- 1594896 TI - Who caused it? Interpersonal causal inferences in young children. AB - Three experiments were designed to test 4- and 6-year-old children's causal inferences in interpersonal settings where emotions (glad, angry, and sad) were effect responses. The results showed that emotion and orientation (towards or away from) were central cues, and that sex and age also were used to some extent. Cues related to regularity philosophic notions (e.g. David Hume), such as contiguity in time and space, and time order of cause and effect were little used by comparison. The results raise questions about the basic role attributed to regularity cues both by philosophers and psychologists, and suggest a multiple cue contribution rather than a basic cue generalization approach to causal cognition development. PMID- 1594897 TI - Blood pressure reactivity to active and passive behavioral conditions in hypertensives and normotensives. AB - Blood pressure reactivity and passive behavioral tasks was studied in patients with mild essential hypertension and normotensive controls. The passive condition included 10 presentations of a 6 sec, 78 dB, 1000 Hz tone without any response requirements. In the active condition subjects were given an additional 10 tone presentations and asked to press a push-button at tone termination. The absolute and percent increase in systolic blood pressure from rest was greater in hypertensives than normotensives in response to the active condition but similar to the passive condition. It is concluded that patients with hypertension compared to normotensive controls show exaggerated blood pressure reactivity to tasks involving active but not passive coping efforts. Since the tasks used to induce active and passive coping in the present study were identical apart from coping requirements, the notion that the activity dimension in and of itself modulates reactivity differences between patients and controls is supported. PMID- 1594898 TI - Women's yielding to social group pressure as a function of alcohol and type of pressure. AB - Thirty-six women participated in an experiment exploring whether alcohol intoxication facilitates yielding to social persuasive information. Subjects were randomly assigned to either an Alcohol, a Placebo, or a Control Group. The alcohol dose was 1.0 ml of 100% alcohol/kg body weight. Subjects first estimated the length of a line and were then given faked feedback from either a male or a female peer reference group. This procedure was repeated 60 times. Analyses indicated that the Placebo group yielded more often than the Alcohol group irrespective of type of feedback. A measure of locus of control indicated no significant mean differences as a function of alcohol group but correlations between externality and yielding were strong for placebo subjects, that is, externally oriented placebo subjects yielded more than internally oriented placebo subjects. This was discussed in terms of feelings uneasiness caused by the discrepancy between feelings of intoxication and information about drink content. PMID- 1594899 TI - Purposive behaviour in cognition and perception: considerations of awareness in memory. AB - The responses to the original article by Ronnberg (1990a) provoked interesting and thoughtful points of view that are covered by Garling (1990), Hjelmquist (1990), Montgomery (1991), and Runeson (1990). These articles do not merely present a different outlook but also provide concepts that are certainly worthy of consideration and add more substance to the general topic under discussion. The purpose of this commentary is to seek an understanding of the ideas presented by the above authors within a synthesis of our views of current conceptualizations in cognition and perception. Each of the original criteria (Ronnberg, 1990a) will be treated in turn. PMID- 1594900 TI - [Toxicity of an organic Germanium compound: deleterious consequences of a "natural remedy"]. AB - Reports mainly from Japan, recommend germanium (Ge)-containing compounds as "anti cancer" and "immunostimulatory" remedies. We report on a 25-tear-old woman with stage II HIV disease who consumed a total of 47 g Ge as Ge-lactate-citrate 18%. She developed severe renal insufficiency (creatinine clearance 7 ml/min/1.73 m2, proteinuria 0.28 g/d) and hepatomegaly. Biopsies revealed tubulointerstitial nephropathy with vacuolar degeneration, mainly of distal tubular epithelia, and severe liver steatosis. Tissue Ge content in kidney and liver biopsy specimens was increased 68-and 140 fold respectively. In agreement with previous reports, renal dysfunction persisted 9 months later (creatinine clearance 11 ml/min/1.73 m2). PMID- 1594901 TI - [Positron-emission tomography (PET) in the evaluation of metabolic processes in the myocardium]. AB - Nuclear cardiology, and in particular myocardial scintigraphy, is used with increasing frequency to detect the presence of ischemia before revascularization by angioplasty or coronary artery bypass grafting. On the basis of recent publications it is evident that there are certain conditions in which conventional diagnostic methods suggest the presence of myocardial necrosis, but there is persistent metabolically active myocardial tissue. One of these conditions is the "hibernating myocardium". Patients with this disease entity will show an improvement in cardiac function after revascularization in over 85% cases. Therefore, the diagnosis of "hibernating myocardium" has a high predictive value. Differentiation between irreversible myocardial necrosis and "hibernating myocardium" is possible by positron emission tomography (PET) combining imaging of myocardial metabolism with imaging of myocardial perfusion. With 30 months, 36 patients with established myocardial infarction and a suspicion of "hibernating myocardium" have been examined in the PET scanner at the Paul Scherrer Institute, Villigen. Images of glucose metabolism were obtained by 18-fluoro-deoxyglucose and perfusion images were obtained using thallium in a first phase (thallium SPECT at rest) and rubidium-82) as a positron emitter in second phase. We were able to identify patterns that suggest the presence of "hibernating myocardium", in 19 of 36 patients (53%). The basic principles and limitations of myocardial positron emission tomography are discussed. PMID- 1594902 TI - [Epidemiological aspects of neurological complications of Lyme borreliosis in Switzerland. A case-control study]. AB - To determine the individual relative risk to neurologically affected patients of infection with Borrelia burgdorferi, within the framework of a multicenter case control study encompassing the four neurological departments of the Universities of Basel, Bern, Zurich and Lausanne, 378 patients and 1134 healthy blood donors serving as controls underwent analysis for antibodies against Borrelia burgdorferi by ELISA. The seroprevalence were estimated for a cut-off point of 2 standard deviations from the mean, these values corresponding to cut-off points of 1:32 for IgM and 1:256 for IgG by immunofluorescence testing. For IgM, 4.8% of the neurological patients were positive versus 4.1% of controls; the corresponding values for IgG were 10.1% versus 10.7% respectively. Hence, neurologically affected patients were not at higher risk for infection with Borrelia burgdorferi than were controls. We found no elevated relative risk in any diagnostic subgroup. The results of a positive Lyme serology must therefore be interpreted with care and in relation to clinical and CSF findings. On the basis of our results, screening for Lyme borrelioses serves no purpose. PMID- 1594903 TI - [Thoracoscopy: diagnostic and therapeutic use]. AB - From 1986 to 1989, we performed 74 thoracoscopies in 70 patients (37 persisting or relapsing pneumothoraces, 30 chronic pleural effusions, 3 primary pleural tumors, 2 chylothoraces, 1 empyema, 1 persisting bronchopleural fistula). 29 supplementary diagnoses were established by thoracoscopy: 11 carcinomas, 4 cases of pleural tuberculosis, 12 of nonspecific pleurisy, 1 pleural fibroma, and 1 hamartoma. Pleurodesis was done with talc under thoracoscopy with success in 32/34 cases of pneumothorax (94%) and in 19/20 patient with chronic pleural effusion (95%). Talc was also successful in 2 instances of chylothorax and the bronchopleural fistula. The empyema was successfully treated by drainage under thoracoscopy and local instillation of streptokinase. Altogether, we recorded 3 deaths in the 30 days following thoracoscopy in 3 plurimetastatic patients. No other major complication was observed. The procedure is a well tolerated tool for diagnosis and treatment of pleural diseases. The indication should however be established with care in debilitated plurimetastatic patients. PMID- 1594904 TI - [Hypothenar hammer syndrome: little-known etiology of secondary Raynaud's phenomenon]. AB - Hypothenar hammer syndrome is an uncommonly encountered cause of Raynaud's phenomenon associated with professional or recreational activities. We report 6 consecutive cases seen in our angiology unit between 1988 and 1990. Clinical findings include a history of repeated microtraumatisms of the dominant hand, male sex, unilaterality, sudden onset, and severe Raynaud's phenomenon of the last three fingers. Investigations reveal an aneurysm or thrombosis of the distal cubital artery or of the superficial palmar branch, associated with occlusion of digital arteries. Avoidance of the aggravating conditions or resection and/or plasty of the affected vascular segment usually leads to disappearance of the symptoms. PMID- 1594905 TI - [Brain and consciousness]. PMID- 1594906 TI - [Bone and joint problems in long-term dialysis]. AB - Bone and joint pathology in patients undergoing long-term dialysis for end-stage renal failure is presented in the light of typical cases and a brief review of the literature. Osteomalacia with bone pain and fractures is caused mainly by aluminium overload due to enteral uptake from aluminium-containing phosphate binders. This is why calcium acetate or calcium carbonate should be used exclusively to lower enteral phosphate reabsorption. If--due to hypercalcemia- aluminium containing phosphate binders--cannot be entirely avoided, they should never be administered together with citrate (citrate-containing medication, fruit juice, etc.), which chelates aluminium and thereby massively increases enteral aluminium uptake. Secondary hyperparathyroidism with overt radiologically demonstrable bone disease develops in many patients on long-term dialysis despite efforts to maintain plasma calcium within or slightly above the upper normal range and concomitant treatment with calcitriol. Intravenous administration of relatively high-dose calcitriol or 1-alpha-OH-D3 (neither readily available at the present time), as well as the newly developed experimental vitamin D analogs such as 22-oxa-(OH)2-D3, which appear to suppress the parathyroid glands without increasing enteral calcium reabsorption, may in future reduce the high incidence of parathyroidectomy in patients on maintenance dialysis. beta 2-microglobulin amyloidosis is a new disease entity which develops in the majority of long-term dialysis patients. Apart from carpal tunnel syndrome, trigger fingers and tendon ruptures, it is associated with acute and chronic painful erosive arthropathy with joint effusions and fractures, particularly around the hip, due to cystic bone lesions where bone is replaced by nodular amyloid deposits.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594907 TI - [Magnetic resonance tomography in malignant genital tumors]. AB - Magnetic resonance imaging (MRI) is a valuable noninvasive method for evaluating the female and male pelvis. The advantages of MRI include direct multiplanar imaging and excellent contrast resolution. The superb soft-tissue contrast provides unique depiction of the characteristic zonal architecture of the uterus, vagina and the prostate. The role of MRI in the pre- and posttherapeutic evaluation of carcinoma of the endometrium, cervix, ovaries, vagina and prostate is described. Our own experience with patients with a suspected tumor recurrence shows that MRI is able to distinguish tumor recurrence from posttherapy fibrosis if the interval between therapy and MRI is more than one year. MRI seems not to be useful in differentiating these entities at an early stage after treatment. PMID- 1594909 TI - [Oral anticoagulants in clinical practice]. AB - Oral anticoagulation (OA) in ambulatory practice is a controversial issue, and the efficacy and safety of its performance is an essential condition for the use of such sophisticated therapy in this setting. The efficacy and use of OA was studied in 24 participating practices over one year (1.4 1987 to 31.3. 1988). Overall, 538 patients were treated by OA, accounting for 22.4 patients/medical practice. OA was initiated in 207 patients, while 287 patients were on longterm (greater than 2 years) anticoagulation therapy. Most patients had polymorbidity, and many presented several indications for OA. On average, thromboplastin time was determined 2.7 times in the first 2 weeks of therapy and every 21 days during the whole period. 72% of measured thromboplastin times were within the target and 90.6% within the therapeutic range. Bleeding complications occurred in 38 patients (7.6%; 11.6/100 treatment years). OA had to be interrupted only 14 times (2.6%; 4.3/100 treatment years), and 7 patients (2.3%; 2.3/100 treatment years) were admitted to hospital. 6 patients died, as compared with 7.5 deaths expected from national mortality rates; none died from complications of OA. Based on these results it can be concluded that OA was highly effective in the 24 participating practices and had a low rate of complications. PMID- 1594908 TI - [Mono-arthritis of uncertain etiology--a follow-up study]. AB - 78 patients in whom the cause of a monoarticular arthritis remained unclear after an initial workup were contacted for a follow-up interview (and an additional clinical examination in 64 cases) after 6 to 11 years (mean 8 years). The mean age at the onset of symptoms was 39 years, with 51% of the patients presenting in the range between 20 and 40 years. There was a slight male preponderance (56%). Large joints, mainly the knee, and less often the wrist, ankle or hip, were affected in 79%. Finger, toe and other small joints were involved in only 21%. During the course of the disease 14% of the cases developed arthritis in other joints. At the time of follow-up an etiologic or nosologic diagnosis was possible only in 5%: 1 infectious Pneumococcus pneumoniae arthritis, 1 Lyme arthritis (Borrelia burgdorferi), 1 gouty arthritis and 1 erosive seronegative rheumatoid arthritis. 95% of all cases remained unclear. However, 91% of all patients became free of symptoms after 6 years. The remaining patients (9%) suffered from arthralgia of undetermined origin (n = 5), from nonclassified destructive coxitis with consecutive development of unclear gonarthritis (n = 1), or from erosive seronegative rheumatoid arthritis (n = 1). 10 patients (13%) underwent a total of 16 invasive procedures related to their arthritis, such as synoviorthesis, synovectomy or arthrodesis. The result of the erythrocyte sedimentation rate had no influence on the outcome. The following conclusions are offered: monoarticular arthritis initially should prompt a thorough investigation in order to exclude infectious or metabolic etiologies for their destructive potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1594911 TI - [Incidence of ileus following rectum resection in rectal carcinoma with or without radiotherapy]. AB - Between 1984 and 1989 240 patients underwent radical abdominal resection of a rectal carcinoma. Out of 201 patients surviving 12 months or more postoperatively, 2 groups are surveyed. The first group presents patients undergoing adjunctive radiation therapy (n = 47), while the second group did not undergo postoperative radiation therapy (n = 134). Mean follow-up time postoperatively is 39 months. Within the irradiation group, the incidence of ileus was found to be 23% (11/47), and in the non-irradiated group 8% (11/134). Subsequent reoperations to clear intestinal obstruction were performed in 4% (5/134) of non-irradiated patients and 21% (10/47) of the irradiated group. Considering the increased risk of postoperative ileus after rectal resection for rectal carcinoma, the appropriateness of adjunctive radiation therapy should be carefully assessed. PMID- 1594910 TI - [Is flexible sigmoidoscopy as preventive measure for colorectal carcinoma in asymptomatic patients over 45 practicable?]. AB - The efficacy of flexible sigmoidoscopy as a screening method for colorectal cancer is still undetermined, and a reduction in mortality due to this cancer by mass screening has not been demonstrated so far. An important precondition for the practicability of screening sigmoidoscopy is its acceptability by the persons to be screened. Acceptability was tested in 294 volunteers without abdominal symptoms from a general medical outpatients clinic. Mean age of participants was 58 years (45-86), 65% were men and 35% women. Sigmoidoscopy was judged harmless by 221 persons (75.1%), painful by 62 (21.1%), very painful by 11 (3.7%), and unacceptable by none. Every participant would have agreed to repeat the examination. In 36 patients 52 polyps were detected, comprising one carcinoma, 18 adenomas (in 15 patients), 32 hyperplastic polyps and one lipoma. We conclude that sigmoidoscopy was well accepted in this study and should be evaluated further as a mass screening method for colorectal cancer. PMID- 1594912 TI - [Swiss Society of Pediatrics annual meeting. Davos, 18-20 June 1992: Abstracts]. PMID- 1594913 TI - [Ethological basis for the evaluation of animal welfare in housing systems for agricultural animals and laboratory animals]. AB - The Swiss Federal Act on Animal Protection (1978) requires the sale of mass produced housing systems for farm animals to be authorized by the Federal Veterinary Office. Authorization is only granted for housing systems that safeguard the animals' welfare. A concept for the assessment of Animal Welfare has to provide a high forensic value. The capacity of farm animals to adapt to an intensive housing system can be directly examined, whereas the existence and extent of subjective feelings can only be assumed. In our concept the examination focuses on the interaction of individuals with their artificial environment. The main question is whether or not the individuals are able to cope with given nonspecific (e.g. temperature, humidity) and specific (e.g. drinking troughs, behaviour of conspecifics) stimuli in order to reach the immediate (e.g. drinking, make way for) and ultimate (survival, reproduction success) goals. Animals of the same breed are observed in a highly diverse environment in order to determine normal behaviour. Whether behavioural expressions which differ significantly from normal behaviour are adaptive to the restrictive housing conditions is judged by the behaviours' consequences for both, the individuals and the environment. Many studies prove the concept's high forensic value and the authorities prefer conclusions based on this concept to others referring to the animals' motivational and emotional state. However more research has to be done with respect to animal welfare in farm and laboratory animal breeding as well as in the use of laboratory animals for experimental studies. PMID- 1594914 TI - [Ethological basis for the development of alternative husbandry systems]. AB - Ethological studies in semi-natural enclosures consistently show that the species specific behaviour of our farm animal species has hardly been changed by domestication. However, in intensive husbandry systems the evolutionary bases of behaviour are neglected. The functions of behaviour are no longer achieved by the animal's species-specific behaviour, but by technical solutions. In contrast, alternative husbandry systems provide the animal an environment that releases and structures its species-specific behaviour. A combined husbandry system for breeding sows and fattening pigs in an enriched pen is described. Although the structures of the pen and the space available differ much from a semi-natural environment, the pigs show their normal species-specific behaviour. This is because the behavioural mechanisms do not respond differently to natural and artificial stimuli in their environment. PMID- 1594915 TI - [Behavioral studies of piglets and rabbits with special consideration of necessary supplies and avoidance of injury]. AB - After introducing remarks on the meaning of the ethology of farm animals about the evaluation of housing systems the own examinations about piglets in the rearing period and about housing systems of rabbits held in groups respectively will be demonstrated. By these examinations choice experiments have proved true. For estimating and evaluating the ethological experimental results the concept of the meeting of requirements and avoidance of damage is an important point. The animals requirement can be found out in reference systems. Those investigated results are used as guiding-line for the evaluation of the dates found under practical conditions. The merits of Tschanz concerning the ethology of farm animals will be appreciated. PMID- 1594916 TI - [The importance of applied ethology for the execution of animal welfare legislation]. AB - Applied ethology in general and farm animal ethology in particular have a great importance in connection with animal welfare regulations on a national and international level. They have through the legislation on animal welfare brought about important repercussions on housing of farm animals, wild animals and experimental animals in Switzerland. The animal welfare legislation has been a considerable boost to scientific research. The application of ethological knowledge in the legislation and in practice has indeed also its limits. The importance of applied ethology for animal welfare and for animal husbandry will still increase in future. PMID- 1594917 TI - Lead in household dust. AB - The lead content of 55 samples of dust collected from vacuum cleaner bags from various parts of Denmark has been determined. The concentrations found ranged from 1.5-48.9 ppm lead in the dry dust, the geometric mean being 9 ppm which is comparable to the mean concentration of lead in Danish arable soil. No correlation was found between traffic density and concentration of lead in the dusts. PMID- 1594918 TI - Changes in levels of hepatic biotransformation enzymes and haemoglobin levels in female plaice (Pleuronectes platessa) after oral administration of a technical polychlorinated biphenyl mixture (Clophen A40). AB - Female plaice (Pleuronectes platessa) were orally dosed with a gelatin capsule containing a solution of the technical PCB mixture Clophen A40 in sunflower oil. They were compared to plaice injected with a gelatin capsule containing only the sunflower oil at 10 and 16 days after injection. Even at 16 days after injection, the increase in concentrations of individual CB congeners in muscle was proportional to their contribution in Clophen A40. Biochemical effects are related to increases in concentrations of well-separable CB congeners in muscle, which increased by factors between 1.6 and 64 compared to the reference group of fish. Of both sampling points, total cytochrome P-450 levels were higher than the control groups, but surprisingly ethoxyresorufin-O-deethylase (EROD) activities did not differ between the groups. Enzyme-linked immunosorbent assay (ELISA) showed increased concentrations of the inducible cytochrome P-450IA1 in PCB treated fish. The apparent lack of EROD induction may be due to competitive substrate inhibition by certain CB congeners present in the sample. The activity of glutathione-S-transferase (GST) (with CDNB as model substrate) was significantly elevated by PCB-treatment at day 16, but not at day 10. A longer time interval between injection with PCBs and induction of GST compared to P-450 monooxygenase activities has been reported earlier and may indicate that in fish both groups of enzymes are regulated individually and not as an [Arylhydrocarbon] gene battery as appears to be the case in mammals. Haemoglobin concentrations and MCHC were decreased in fish treated with Clophen A40. Haematocrit values did not differ between groups of fish. PMID- 1594919 TI - Occupational exposure to carbon monoxide during charcoal meat grilling. AB - Charcoal meat grill workers are one of the many occupational groups that are subject to carbon monoxide exposure. This group have often been overlooked and not investigated. Carboxyhemoglobin (%COHb) levels in 100 male workers were assessed before work and after work the same day. Carboxyhemoglobin levels increased significantly after work in both smoking and nonsmoking workers. The mean COHb levels for smoking workers before work was 3.8% and for nonsmokers was 2.4%, whereas after work, the mean COHb level for smokers increased to 8.1% and for nonsmokers to 6.2%. These elevated mean COHb levels exceed the 5% COHb level recommended by WHO and NIOSH. With respect to smokers only, 36 (81.8%) workers after work exceed 5%, whereas the nonsmokers, 29 (51.8%) of the workers exceed 5%. These results indicate that charcoal meat grilling workers are exposed to significant levels of carbon monoxide. Several control measures have been suggested to mitigate exposure to carbon monoxide. PMID- 1594920 TI - Trace elements in scalp hair of manufacturers of fireworks from Sivakasi, Tamil Nadu. AB - The concentrations of Cd, Cr, Cu, Mn, Ni and Pb were analysed by AAS in the hair of male and female, controls and workers from firework cottage industries from Sivakasi, Tamil Nadu. When compared with controls, significantly higher levels of Mn and Cr were found in male healthy workers and unhealthy workers with chronic headaches and dizziness. In the case of female workers, higher Mn and lower Pb levels were found, but the level of any element was not significantly different in the workers with ulcers and asthma. There is a possibility of occupational exposure of both male and female workers to the risk of Cr and Mn pollution. PMID- 1594921 TI - Elaboration of a water ichtyologic potential index. AB - A model has been developed, using physico-chemical data, in order to quantify the quality of surface waters and their ichtyologic potential: the WIPI model (Water Ichtyologic Potential Index). Many physico-chemical parameters, useless if considered individually, can be of practical interest for pisciculture (e.g., an explanation of systematic fish mortalities, elaboration of guidelines for new pisciculture). The water quality is expressed in terms of an eight-step scale that provides a guide evaluation of the ichtyologic potential. PMID- 1594922 TI - Long-range changes in oxytetracycline concentration and bacterial resistance toward oxytetracycline in a fish farm sediment after medication. AB - Following 10 days medication with oxytetracycline, marine sediment was sampled beneath three selected cages (cages 1, 2 and 3) at a fish farm over a period of 18 mnd., in order to detect any change in the sediment oxytetracycline concentration, bacterial number and bacterial resistance towards the drug. The bulk of oxytetracycline disappeared during the first weeks, but it persisted in the sediment at lower concentrations for quite some time after the medication. Half-life (t(1/2)) of oxytetracycline in the sediment was measured as: 125, 144 and 87 days under cages 1, 2 and 3, respectively. At the end of the medication, all three sediments had greater than 100% oxytetracycline-resistant bacteria. This value dropped to 20% after 72 days and stabilised at levels of between 10 and 50%. The change in bacterial numbers, described as total and plate counts, was due to seasonal variations rather than to the medication. PMID- 1594923 TI - Sources and atmospheric concentrations of polycyclic aromatic hydrocarbons and heavy metals in two Italian towns (Genoa and La Spezia). AB - The same sampling and analytical methods were used to compare atmospheric pollution due to polycyclic aromatic hydrocarbons (PAHs) and heavy metals (Tl, Pb, Mn, Fe, Cr, V, Zr, Ni Cd) in two towns in Italy, Genoa and La Spezia, whose populations are 746, 785 and 112,602 respectively. Knowledge of the organic and inorganic composition of airborne particulates permits a reliable identification of the main sources of pollution which is required in order to identify populations at risk. In the urban area of Genoa and in La Spezia, traffic appears to provide a diffuse source of carcinogenic and toxic compounds in the atmosphere producing high and constant exposures to PAHs and lead along busy streets. In Genoa approximately 70,00 people (10% of residents) are considered to be exposed to the highest concentrations of toxic and cancerogenic pollutants emitted from this source. The highest daily PAH concentrations were found in the industrial areas; in Genoa, coke ovens were identified as the main localised sources of these compounds. According to meteorlogical and orographic characteristics for this area, for approximately 25,00 people (3% of the general population) may be exposed to pollutants emitted from this source over a maximum period equivalent to approximately 3 months each year. The highest individual doses of PAHs due to urban pollution inhaled by the population of Genoa and La Spezia were comparable to those produced by high exposure to passive smoke; the exposure to carcinogenic metals (Cr, NI, Cd) was relatively low. The mean concentrations of the analysed pollutants appeared to depend strictly on urban characteristics; no correlations were found with the size of the town. PMID- 1594924 TI - Cadmium, lead and mercury levels in feeding yeast produced in Czechoslovakia. AB - Ninety-six samples of the feeding yeast known as VITEX were analyzed for Cd, Pb and Hg content during 1987-1989. Cadmium content ranged from 0.30 to 5.12 mg/kg( 1), lead content from 0.21 to 3.01 mg/kg(-1) and mercury content from 0.008 to 0.187 mg/kg(-1). Our findings meet the current government standards (max. allowed Pb = 5.00, Cd = 0.50 and Hg = 0.100 mg/kg(-1)) only for lead, and with five exceptions, for mercury. With two exceptions, all cadmium levels found in the samples exceeded the limit. One raw material - the wood chips - was shown to be the main source of cadmium in the technological process. Relatively high Hg contents were measured in the wood chips (up to 0.155 mg/kg(-1)); the highest Hg level (1.105 mg/kg(-1)) however was found in a sample of KOH. PMID- 1594925 TI - Chemical and radiological risk factors associated with waste from energy production. AB - We have tried to estimate the toxic potential of waste from nuclear power plants and from power plants burning fossil fuels. The potential risks have been expressed as 'risk potentials' or 'person equivalents.' These are purely theoretical units and represent only an attempt to quantify the potential impact of different sources and substances on human health. Existing concentration limits for effects on human health are used. The philosophy behind establishing limits for several carcinogenic chemicals is based on a linear dose-effect curve. That is, no lower concentration of no effect exists and one has to accept a certain small risk by accepting the concentration limit. This is in line with the establishment of limits for radiation. Waste products from coal combustion have the highest potential risk among the fossil fuel alternatives. The highest risk is caused by metals, and the fly ash represents the effluent stream giving the largest contribution to the potential risk. The waste from nuclear power production has a lower potential risk than coal if today's limit values re used. If one adjusts the limits for radiation dose and the concentration limit values so that a similar risk is accepted by the limits, nuclear waste seems to have a much higher potential risk than waste from fossil fuel. The possibility that such risk estimates may be used as arguments for safe storage of the different types of waste is discussed. In order to obtain the actual risk from the potential risk, the dispersion of the waste in the environment and its uptake and effects in man have to be taken into account. PMID- 1594926 TI - Natural radiation--a perspective to radiological risk factors of nuclear energy production. AB - Radiation doses from natural radiation and from man-made modifications on natural radiation, and different natural radiological environments in the Nodic countries are summarized and used as a perspective for the radiological consequences of nuclear energy production. The significance of different radiation sources can be judged against the total collective effective dose equivalent from natural radiation in the Nordic countries, 92,000 manSv per year. The collective dose from nuclear energy production during normal operation is estimated to 20 manSv per year and from non-nuclear energy production to 80 manSv per year. The increase in collective dose due to the conservation of heating energy in Nordic dwellings is estimated to 23,000 manSv per year, from 1973 to 1984. An indirect radiological danger index is defined in order to be able to compare the significance of estimated future releases of radionuclides from a final repository of spent nuclear fuel to the consequences of natural radionuclides in different environments. The danger index of natural radiological environments will not be significantly increased by future releases of nuclear fuel radionuclides. PMID- 1594927 TI - The pathology of phocine distemper. AB - The gross and microscopic pathology of phocine distemper is described. The most striking features were pulmonary congestion and emphysema associated with proliferation of type II pneumocytes, often forming syncytia. Secondary bacterial infection was common and associated with marked atrophy of lymphoid tissues and degenerative changes in the mucosa of the airways. PMID- 1594928 TI - Molecular and serological studies on the recent seal virus epizootics in Europe and Siberia. AB - The virus epizootics which occurred in seals in both Europe and Siberia during 1987/1988 were caused by two different morbilliviruses, referred to as phocid distemper virus (PDV) 1 and 2, respectively. Molecular and serological studies have shown that the European virus is quite distinct from canine distemper virus (CDV), its closest relative in the morbillivirus group. Analysis of tissues obtained from infected seals from a wide geographical distribution over Northern Europe showed that the infectious agent (PDV 1) was identical in all cases. Nucleotide sequence analysis of one of the virus genes suggested that this virus has evolved away from CDV over a long time period and is most probably an enzootic virus of marine mammals. In contrast, the virus (PDV 2) which caused the deaths of many Siberian seals was indistinguishable, both serologically and at the molecular level, from CDV and must have originated from a land source. PMID- 1594929 TI - Plasma thymulin concentrations, the thymus and organochlorine contaminant levels in seals infected with phocine distemper virus. AB - Blood samples collected from live common seals (Phoca vitulina) and grey seals (Halichoerus grypus) around the coast of Scotland and Northern Ireland during, and immediately after, an epizootic caused by phocid distemper virus (PDV) were analysed for thymulin content. Thymulin levels were compared with neutralization titres and concentrations of organochlorine contaminants (DDT and its metabolites, seven chlorinated biphenyl congeners) derived from blood and blubber samples collected from the same animals and analysed independently. Thymulin levels in grey seals (mean 2827 +/- 1355 fg/ml) were negatively correlated with the logarithm of virus neutralization titre. In common seals they varied significantly between age classes. There was no direct relationship between thymulin levels and contaminant levels in either species. However, when an estimate of time since exposure was included in the regression analysis for common seals, there was a highly significant relationship between thymulin and the two chlorinated biphenyl congeners with the highest concentrations in blubber. PMID- 1594930 TI - Organochlorine levels in common seals (Phoca vitulina) which were victims and survivors of the 1988 phocine distemper epizootic. AB - We compared concentrations of organochlorines in the blubber of common seals (Phoca vitulina) found dead during the 1988 phocine distemper epizootic with levels in animals which survived it. There were highly significant differences between the live and dead animals, and between sample sites. These were not fully accounted for by seasonal and condition-related changes in blubber thickness. PMID- 1594931 TI - Quantitative investigations of the epidemiology of phocine distemper virus (PDV) in European common seal populations. AB - This paper uses simple mathematical models to examine the long-term dynamic consequences of the 1988 epizootic of phocine distemper virus (PDV) infection in Northern European common seal populations. In a preliminary analysis of single outbreaks of infection deterministic compartmental models are used to estimate feasible ranges for the transmission rate of the infection and the level of disease-induced mortality. These results also indicate that the level of transmission in 1988 was probably sufficient to eradicate the infection throughout the Northern European common seal populations by the end of the first outbreak. An analysis of longer-term infection dynamics, which takes account of the density-dependent recovery of seal population levels, corroborates this finding. It also indicates that a reintroduction of the virus would be unlikely to cause an outbreak on the scale of the 1988 epizootic until the seal population had recovered for at least 10 years. The general ecological implications of these results are discussed. PMID- 1594932 TI - Tissue concentrations of organochlorine compounds in common seals from the coast of Northern Ireland. AB - An epizootic of morbillivirus infection killed several hundred common seals (Phoca vitulina) along the coast of Northern Ireland in 1988. Many dead and moribund seals were submitted to the Department of Agriculture for Northern Ireland, Veterinary Research Laboratories for necropsy. Samples of blubber, liver and kidney were collected from these animals (n = 55) for analysis for a wide range of organochlorine pesticides and also total polychlorinated biphenyls (PCBs). The organochlorines found in highest concentrations in blubber were PCBs which were detected in all samples (mean, 26 micrograms g-1 wet wt). sigma DDT (mean, 2.63 micrograms g-1 wet wt) and chlordane (mean, 0.22 micrograms g-1 wet wt) were also present in all samples. Heptachlor including heptachlor epoxide (mean, 0.13 micrograms g-1 wet wt) was present in over 93% of samples. Seventy four percent of samples contained alpha HCH (mean, 0.035 micrograms g-1 wet wt), 50% contained beta HCH (mean, 0.026 micrograms g-1 wet wt) while gamma HCH (mean, 0.012 micrograms g-1 wet wt) was detected in 46% of samples. The organochlorine concentrations found in this study are at the lower end of the range previously reported for European common seals. PMID- 1594933 TI - The descriptive epizootiology of phocine distemper in the UK during 1988/89. AB - The 'time, place, individual' approach, widely used in characterising human epidemics, was applied to the 1988 phocine distemper virus (PDV) epizootic affecting North Sea seals. Estimates of time of death from 157 (69%) of the 228 dead seals necropsied in 1988 indicated that the number of carcasses which were found more than 14 days post mortem increased as the epizootic progressed. Although information provided by epizootic curves based on when and where carcasses were reported are affected by the accuracy of such data, the PDV epizootic curves were characteristic of a propagative epidemic. The individual characteristics of the carcasses provided more useful information. 1. Common seals were more susceptible than grey seals. 2. Males and older seals had a greater exposure to the virus than females and younger animals. 3. The likelihood of viral transmission was greater on land. Seasonal, sex and age related variation in haul-out behaviour affected transmission probabilities and rates. 4. The risk of infection for a susceptible individual during August was higher for seals in England and Northern Ireland than for those in Scotland. These findings illustrate the importance of population characteristics including behaviour and social organisation in determining the pattern and spread of wildlife epizootics. PMID- 1594934 TI - Phocine distemper virus, the agent responsible for the 1988 mass mortality of seals. AB - The biochemical characterisation of phocine distemper virus (PDV) has shown that PDV is related to but clearly distinct from canine distemper virus (CDV) and relative to its relationship with CDV is only remotely related to the other morbilliviruses, namely measles virus (MV) or rinderpest virus (RPV) and peste des-petits-ruminants virus (PPRV). Comparative studies with monoclonal antibodies indicate that the virus is serologically closely related to CDV with many conserved epitopes, particularly on the internal proteins of the virus, while the external attachment (H) protein shows the greatest level of variability among the distemper virus isolates. The analysis of the viral proteins by electrophoresis indicates molecular weight differences between CDV and PDV in the fusion (F), phosphoprotein (P), H, nucleocapsid (N) and matrix (M) proteins. The RNA profiles of CDV and PDV are indistinguishable and different from those for RPV and MV. Nucleotide sequence analysis of cDNA clones of the virus show approximately 70% homology between CDV and PDV and approximately 48% with MV. These data prove that PDV is a different virus from CDV and co-circulates with it probably primarily in sea mammals. PMID- 1594935 TI - Phocine distemper virus outbreak in the Moray Firth common seal population: an estimate of mortality. AB - Changes in abundance at haul-out sites were followed, and data on the number of deaths collected, to describe the pattern and extent of mortality resulting from the 1988 phocine distemper virus outbreak in the Moray Firth common seal population. Mortality in this population was estimated to be between 10% and 20%, and was low in comparison to some other parts of the North Sea. Most deaths occurred in the 3-month period from 1st August 1988, and there was no sign of a resurgence of the disease during the 1989 breeding season or moult. PMID- 1594936 TI - Disease conditions affecting common seals (Phoca vitulina) around the Scottish mainland, September-November 1988. AB - Common seal populations around the Scottish coast were less severly devastated by phocine distemper than those on the Continent. Nevertheless, over a 4-month period, 59 common seals were examined postmortem. The macroscopic and histopathological lesions are described. Forty-two per cent of these seals were considered to be suffering from phocine distemper. Serology on 29 of the 59 seals was undertaken and the results are discussed in relation to the histopathological findings. Bordetella bronchiseptica proved to be an important secondary invader in phocine distemper virus infected seals. Verminous pneumonia was shown to be a frequent problem, particularly in juveniles. PMID- 1594937 TI - Immune responses in common and grey seals during the seal epizootic. AB - Serological surveys of common and grey seals were performed to monitor the spread of the phocid distemper outbreak in 1988 and its effects on the host immune response. The disease affected mainly common seals; grey seals were largely unaffected but did have anti-CDV antibodies which developed during 1988. Canadian seals, both common and grey, showed evidence of a morbillivirus infection but without the apparent mortality observed in British common seals. Common seal circulating immunoglobulin levels were not greatly affected during the outbreak, although there was some reduction in the most severely affected pups. Vaccination of common seals with CDV antigens elicited high titres of antibodies and produced clinical protection. Vertical transmission of host immunity was shown in grey seals although the longevity of protection has not been determined. The large population of common seals which are not immune emphasises that such an epizootic could have serious consequences again in the future. PMID- 1594938 TI - The role of bacteria in phocine distemper. AB - The death of many seals believed to be infected with phocine distemper virus was found to be associated with a variety of mainly opportunistic bacterial pathogens. The bacteria most frequently involved were Bordetella bronchiseptica, Corynebacterium species and a variety of Streptococci. Seals dying on different parts of the coast of Britain were infected with these organisms in differing proportions. PMID- 1594939 TI - Demonstration of antibodies in archival sera from Canadian seals reactive with a European isolate of phocine distemper virus. AB - Sera from seals infected during the 1988 European epizootic of phocine distemper virus and sera from Canadian seals collected since 1972 have been tested for the presence of antibodies to morbillivirus. Approximately one third of the Canadian sera have been shown to contain anti-morbillivirus antibodies; the possibility that these populations of seals provided a source of infection for European seals is discussed. PMID- 1594940 TI - The serological response of the common seal (Phoca vitulina) and the grey seal (Halichoerus grypus) to phocine distemper virus as measured by a canine distemper virus neutralisation test. AB - The application of a canine distemper virus (CDV) neutralisation test revealed that antibody titres of up to 11,620 were present in the sera of common seals during the epizootic of phocine distemper in British waters. However, during the later stages of the epizootic and afterwards, a surprisingly high proportion of animals were still seronegative. Titres of from 90 to 183 were common in diseased animals and were probably indicative of partial immunosuppression. A few animals with proven phocine distemper had titres of less than 64, this being evidence of a more profound immunosuppression. Recovered animals tended to have moderate to high titres and in some cases these persisted for at least 6.5 months. By contrast, the administration of an inactivated CDV vaccine produced antibody which declined rapidly to very low levels within the same period. Infection also occurred in grey seals in 1988 but without severe mortality. Antibody titres in this species nearly always lay in the range 128-734 and persisted at or around this level for at least 12 months. In both common and grey seals, antibody was transferred by suckling from mother to pup but absorption by the pup seemed to take place more slowly than in domestic mammals. PMID- 1594941 TI - Cis-urocanic acid as a mediator of ultraviolet-light-induced immunosuppression. AB - Treatment of an organism with UVB light or PUVA (8-methoxypsoralen + UVA light) not only leads to alterations in the irradiated skin but also to systemic immunomodulation, due to the release of several chemical mediators of immunosuppression like prostaglandins, acute-phase proteins, IL-1 inhibitor, alpha-melanocyte-stimulating hormone, propiomelanocorticotropin or other cytokines. A recently described mediator is urocanic acid, which is transformed by UV light in the skin from the trans- to the cis-isomer and that exerts a systemic immunomodulatory effect. In our experiments, treatment with PUVA or with cis-urocanic acid prevents the rejection of rat heart allografts in 50% and 40% of cases, respectively. Control grafts are rejected in fewer than 10 days. PUVA treatment of donor leukocytes before transfusion into the prospective recipient inhibits only their sensitizing, not their graft-protecting, effect on subsequent skin grafts in mice. PUVA treatment also prevents acute lethal GVH disease in mice after irradiation with a sublethal dose of x-rays and transfusion of semiallogeneic spleen cells. Treatment of recipient mice with cis-urocanic acid has the same effect. The humoral immune response to sheep erythrocytes is not influenced by cis-urocanic acid. These results demonstrate that PUVA treatment or its chemical mediator, cis-urocanic acid, may be used in transplantation and hematology as naturally occurring immunosuppressive agents, especially for the control and manipulation of GVH leukemia reaction. PMID- 1594943 TI - Ultraviolet-B irradiation of platelet concentrates: a strategy to reduce transfusion recipient allosensitization. PMID- 1594942 TI - Psoralen plus ultraviolet A (PUVA) in the treatment of chronic graft versus host disease: preliminary experience in standard treatment resistant patients. PMID- 1594944 TI - The effect of ultraviolet B light on antigen-presenting cells: implications for transfusion-induced sensitization. PMID- 1594945 TI - Extracorporeal photochemotherapy for cutaneous T-cell lymphoma and other diseases. AB - Extracorporeal photochemotherapy is an effective method for the treatment of CTCL. It is most effective in the erythrodermic stages of the disease but may also have a place in the treatment of more advanced disease. Phototherapy has also been used in the treatment of other T-cell-mediated diseases. Psoralen plus UVA are known to interact with cellular DNA, proteins, and lipids. The mechanism of action is not completely understood but there is suggestive evidence that cell membrane changes so caused can render the cell susceptible to immune surveillance and destruction. PMID- 1594946 TI - Photodynamic therapy of solid tumors. PMID- 1594947 TI - Introduction: photomedicine--to use the power of light. PMID- 1594948 TI - Antiviral effects of photosensitizing merocyanine dyes: implications for transfusion and bone marrow transplantation. PMID- 1594949 TI - Structure-activity relationships in the antiviral and antileukemic photoproperties of merocyanine dyes. PMID- 1594951 TI - [Mechanisms at the origin of vesico-sphincteral disorders]. PMID- 1594950 TI - Modification of allointeractions after blood transfusion and marrow transplantation by ultraviolet light. PMID- 1594952 TI - [Symptomatology of urinary incontinence]. PMID- 1594954 TI - [Drug and surgical treatment of urinary incontinence]. PMID- 1594953 TI - [Urinary incontinence in the aged. Complementary tests]. PMID- 1594955 TI - [The bladder sphincter evaluation test]. PMID- 1594956 TI - [A calendar or catalog of urination]. PMID- 1594957 TI - [Products for comfort]. PMID- 1594958 TI - [Urinary incontinence in the aged. Epidemiology]. PMID- 1594959 TI - [Urinary incontinence in the aged]. PMID- 1594961 TI - [Urinary incontinence in the aged. The problems arising on admission]. PMID- 1594960 TI - [The nursing process and incontinence in the aged]. PMID- 1594962 TI - [Urinary incontinence in the aged. A means of non-verbal communication]. PMID- 1594963 TI - [Nursing activities and ethical activities]. PMID- 1594964 TI - [Dietetics: a long story]. PMID- 1594965 TI - [The health care system: a salutary crisis?]. PMID- 1594966 TI - [The hospital St. Lazare]. PMID- 1594967 TI - [Physiology of micturation]. PMID- 1594968 TI - [Who are you, Michelle Pohier?]. PMID- 1594969 TI - [The aminoglycosides]. PMID- 1594970 TI - [Tubing and stopcock protector. Protective cover]. PMID- 1594971 TI - [The urinary tract: anatomical recall]. PMID- 1594972 TI - Outcome of schizophrenia in the Afro-Caribbean community. AB - It has been suggested that atypical psychoses of good prognosis might account for the high rates of schizophrenia in the Afro-Caribbean community in Britain. In this study 39 Afro-Caribbean admitted with RDC schizophrenia were followed up in the community, as were matched white subjects. Psychological and social impairments were similarly severe in both groups, showing that schizophrenia among Afro-Caribbeans in Britain is not marked by a favourable outlook. This finding has major implications both for our understanding of the aetiology of schizophrenia, and for the provision of psychiatric services. PMID- 1594973 TI - The Dubai Community Psychiatric Survey: I. Prevalence and socio-demographic correlates. AB - This paper describes the methods and initial sociodemographic findings of the first community psychiatric survey from an Arabian country. It was carried out on a sample of women in Dubai, one of the seven United Arab Emirates. Psychiatric status was established using the PSE-ID-CATEGO system. The overall prevalence of disorder in these women was a high 22.7% (13.7% depressive disorders; 7% anxiety states). There was little association with sociodemographic variables, except that prevalence was high in divorced, widowed and separated women, polygamously married women and single parents. The high prevalence may be related to the rapid sociocultural change in this society. Future reports will examine the influence of sociocultural change at an individual level. PMID- 1594974 TI - Sex differences in mental illness: a community study of the influence of physical health and sociodemographic factors. AB - This paper examines sex differences in psychiatric morbidity, using data from a community sample. The PSE-CATEGO-ID system was used to evaluate psychopathology. Six sociodemographic factors and physical illness were taken as independent variables. Females exhibit both a significantly higher psychiatric morbidity than males and a predominance of syndromes closely related to depression (SD; OD syndromes) and anxiety (GA; SA; TE; IT syndromes). Logistic modelling analysis, carried out separately for each sex, yielded different models. Psychiatric illness in men was best predicted by physical illness, unemployment and the interaction between the two. In contrast, physical illness emerged, in women, as the only factor exerting significant effects on psychiatric morbidity. PMID- 1594975 TI - Suicide in the Canary Islands: standardized epidemiological study by age, sex, and marital status. AB - The authors analyze the distribution of suicides according to the variables of sex, age and marital status in the Canary Islands, during the period 1977-1983, by means of a register that they themselves created in order to correct serious deficiencies in the official data. There were notable differences between men and women, and the tendencies observed in each case are also very different. The authors argue that this makes it necessary to separate the sexes in the epidemiological studies on suicide. The advantages and disadvantages of the direct and indirect methods in the standardization of the specific suicide rates are discussed. The specific rates related to marital status are standardized according to age and, likewise, the specific rates related to age are standardized according to marital status, for each sex. Once confounding factors are controlled, it becomes clear that there is a direct relationship between age and suicide. After adjusting for age, it is noted that the pattern of risk for different marital status categories varies by sex. PMID- 1594976 TI - State initiatives in addressing youth suicide: evidence for their effectiveness. AB - An examination of the period from 1980 to 1987 revealed that state government initiatives were, in general, associated with a beneficial effect on teenage suicide rates in the states of America. Student participation in school-based suicide prevention programs, however, was associated with a detrimental effect on state teenage suicide rates. The implications of these results were discussed. PMID- 1594977 TI - Assessing impairment in patients with panic disorder: the Sheehan Disability Scale. AB - The DSM-III-R incorporates both distress (symptoms) and disability (impairment) in the definition of a psychiatric disorder. In psychiatric research there is a wide array of instruments used to measure symptom severity, but a limited selection for the assessment of impairment. The psychometric properties of one such instrument, The Sheehan Disability Scale (Sheehan 1983), are evaluated in this paper. The data analyzed come from two studies of patients with panic disorder, the Cross National Collaborative Panic Study--Phase I and the Panic Depression Study. In this report both the alpha coefficients and factor analyses indicate that the reliability of the scale is acceptable. The factor structure of the items and the sensitivity to change of their composite demonstrate satisfactory construct validity. The criterion-related validity is substantiated by the significant relationship between symptomatology and impairment. These analyses were limited to patients with panic disorder. Further work is needed to evaluate the instrument in assessing patients with other disorders. PMID- 1594978 TI - Social indicators and the prediction of psychiatric inpatient service utilisation. AB - The relationship between social variables and psychiatric service use in Victoria was investigated using a social indicators approach. Indicators were developed separately for the urban and rural areas of the state using 1986 census data. Principal components analysis was employed to reduce the data. Simple, unit weight indicators were developed and explained a considerable proportion of the variation in the rate of persons admitted to psychiatric facilities, the rate of admission episodes and the rate of occupied bed days for urban areas; a moderate amount of variation for these measures was accounted for by indicators developed for rural areas. The findings were considered in relation to both methodological issues and the role of other factors (e.g., accessibility and availability of psychiatric services) which may contribute to service use. PMID- 1594980 TI - [Changes in portal circulation in experimental prehepatic portal hypertension]. AB - In a long-term experiment on dogs the lumen of the portal vein was reduced to one fifth by insertion of a metal spiral. The thus created disorder of the portal circulation was succeeded by the development of abundant hepatofugal collaterals and the development of mild portal overpressure without clinical manifestations. The altered portal circulation was followed up by dynamic hepatobiliary scintigraphy for a period up to 12 months. It was revealed that the curve of isotope movement through the liver was altered in a way suggesting slower perfusion of the liver by portal blood. This observation resembles those in patients with prehapatic portal hypertension and their confirmation. The investigation is documented by morphological, X-ray and isotope methods. PMID- 1594979 TI - Psychotropic medication and ethnicity: an inpatient survey. AB - A survey of the catchment area psychiatric inpatient population of the Bethlem and Maudsley Hospitals showed that more black (Afro Caribbean) than non-black (white British) patients received anti-psychotic medication. This finding ceased to be significant after adjustment for diagnosis because a larger proportion of black than non black patients received a diagnosis of schizophrenia. However, after adjustment for diagnosis, black patients were significantly more likely to be receiving depot anti-psychotic medication, to be detained under a section and to have been involved in a violent incident during the present admission. There were no significant ethnic differences in total dose equivalents of anti psychotic medication but doses of the depot form were significantly higher for black patients. PMID- 1594981 TI - [Partial mastectomy in the treatment of breast cancer]. AB - In the submitted paper the authors summarize findings on conservative surgery in the treatment of breast cancer. Based on data in the literature and their own experience with surgical treatment of breast cancer of all stages and a detailed analysis of a group of 52 conservatively treated patients, the authors discuss indications for this treatment which must respect staging, typing and grading of tumours as well as attitudes of patients. In particular in tumours classified as T1, NO, MO (as well as T2, NO, MO up to 3 cm) with a non-central localization it is possible by using conservative surgery to avoid somatic mutilation and psychic sequelae of radical procedures. When an individual approach is used and the correct indication is selected, partial mastectomy with dissection of the axilla and postoperative radiotherapy is equivalent to therapeutic results of radical operation. PMID- 1594982 TI - [Catabolism after direct myocardial revascularization]. AB - The objective of the investigation was to assemble more knowledge of catabolic processes after cardiosurgery. In 14 patients after 6-hour intervals following an aortocoronary bypass the total production of urea nitrogen, Bistrian's catabolic index and the sodium:potassium ratio in urine was assessed. The urea nitrogen production varied within a range of 5.4-9.5 g per 12 hours. These values when calculated per 24 hours are 94-108 g of protein. The catabolic index was in the range of 5.8-11.2, i.e. within the zone of intense stress. Also the values of the Na/K ratio (1.0-1.9) suggested intense stress. The authors discuss the causes and possibilities to relieve the stress response. PMID- 1594983 TI - [A surgical technique for partial mastectomy]. AB - The authors are describing the technique of the partial mastectomy for the breast cancer in this work, as used in the Masaryk oncological institute. For easy understanding they are adding illustrations of the singular phases of this operation. They are also discussing the indications and are showing a short historical review of the authors having published the results of this surgery. PMID- 1594984 TI - [Surgical treatment of post-traumatic thrombosis of the inferior vena cava]. AB - A 49-year-old man contracted a fracture of the 8th and 9th rib on the right side and developed after this injury thrombosis of the inferior vena cava in the renal and suprarenal portion and of both renal veins manifested clinically as nephrotic syndrome of obscure aetiology. Only detailed cavographic and CT examination revealed this thrombosis. Caval thrombectomy was performed according to Spencer's method because of concurrent phlebothrombosis of the left lower extremity. The patient is in a satisfactory condition with permanent Pelentan medication. PMID- 1594985 TI - [Nosocomial infections in surgical intensive care of multiple injuries]. AB - The authors present an abridged version of the final report of a State research programme. By introduction of a series of provisions and expedient use of funds available for research it proved possible to reduce the incidence of nosocomial infections in surgical patients from 14% to 12% and in a group with multiple injuries in the surgical intensive care unit from 18% to 10%. PMID- 1594986 TI - [Present experience with surgical treatment of medullary carcinoma of the thyroid gland]. AB - Between June 1 1975 and Dec. 31 1989 at the surgical clinic for adults in Prague Motol 44 patients were operated on account of medullary cancer of the thyroid gland (MCT). In the great majority total thyroidectomy (TTE) was performed which in this disease is an absolute indication. In some instances the operation was supplemented by lymphadenectomy. The prognosis of the familial type of the disease was more favourable due to the possibility of active screening of the tumour. The authors reached the conclusion that the therapeutic results in MCT can be improved by early diagnosis as well as sufficiently radical surgical operations. PMID- 1594987 TI - [The role of the vascular surgery department in injury revascularization]. AB - The authors submit the case-histories of five casualties subjected to successful revascularization operations incl. complete treatment of the other injuries. They emphasize the importance of early and accurate diagnosis, immediate and correct assessment of the severity of the injury in relation to possible treatment depending on the conditions and experience of the given department. PMID- 1594988 TI - [Ultrasonography in urologic ambulatory care]. AB - Ultrasonography holds an important place in urological diagnostics. The number of urological departments which have their own apparatus is increasing. So far, however, the opportunity of ultrasonic examination in routine practice of the urologist in out-patient departments is not common, despite the fact that it would be a great asset. In order to make maximum use of ultrasonographic equipment in the urological out-patient department is important to know also some potential negative aspects. Therefore the authors present their experience and compare it with data in the professional literature. The authors demonstrate on examples the impact of ultrasonography on diagnostic algorithms of some urological diseases. PMID- 1594989 TI - [Thoughts on surgery]. PMID- 1594990 TI - [Diverticulosis of the small intestine]. AB - The authors describe a case of a patient who has reoperated for generalized peritonitis shortly after elective inguinal hernia repair. The cause of peritonitis was small bowel diverticulosis with a ruptured diverticulum. PMID- 1594991 TI - [Ligament injuries of the superior tibiofibular joint and their care in type I polyclinic hospitals]. AB - The author analyzes the possibilities of accurate diagnosis of acute injuries of soft tissues, in particular ligaments of the superior tibiofibular joint and compares different diagnostic methods. he draws attention to the sequelae of inadequate treatment when the symptoms of the injury, in particular in young people and sportsmen, are underrated. The author presents then experience from his department with the diagnosis of ruptured ligaments by means of socket symptoms. As regards treatment he prefers in total ruptures a surgical approach and submits the results from his catchment area of a hospital and policlinic type I during the past four years. PMID- 1594992 TI - [The Varix Set--instruments for varices surgery]. AB - The authors describe new, modern instruments for the operation of varicosities, a VARIX set of their own design. The complex of instruments makes sparing and cosmetically effective strisping of the trunk of the large and small saphenous vein possible, as well as extirpation of collateral branches and epifascial severing of perforator veins. Operation with these instruments is easy, safe and sparing for surrounding tissues. PMID- 1594993 TI - [Advantages of alginate bandages for coverage of extensive and poorly healing wounds]. AB - The authors recommend a calcium alginate sterile bandage SORBALGON, its advantage being that it has a haemostatic action, does not irritate tissues, is non-toxic, is easily changed and promotes healing. It is suited for covering extensive and deep wounds with ample secretion. PMID- 1594994 TI - [Late pseudocysts of the spleen and their surgical treatment]. AB - The authors present their experience with the treatment of late posttraumatic pseudocysts of the spleen. They recommend surgical revision of confirmed pseudocysts of the spleen and, depending on the peroperative finding, selection of optimal surgery. They do not recommend percutaneous punctures of late postoperative pseudocysts of the spleen. PMID- 1594995 TI - [Primary adenocarcinoma of the appendix]. AB - The authors published experience with the treatment of four patients with primary adenocarcinoma of the appendix and an analysis of 20 patients with primary adenocarcinoma of the appendix treated in the North Moravia region during a ten year period (1980-1989). The incidence of the disease is rare. Usually it is manifested by symptoms imitating acute appendicitis. In exceptional instances there are other symptoms such as melaena, invagination, infiltration of neighbouring organs etc. Only rarely the disease is diagnosed during appendectomy. Most frequently an adenocarcinoma of the colonic type is involved with a tendency of rapid local spread. In that case right-sided hemicolectomy is the method of choice. In exceptional instances simple appendectomy is sufficient (mucinous type of adenocarcinoma, Dukes A). In advanced stages of the disease a palliative surgical operation may frequently suffice. Radiotherapy and chemotherapy should be always considered with regard to the stage of the disease and the general state of the patient. The prognosis is similar as in adenocarcinoma of the colon. PMID- 1594996 TI - [Use of a distraction apparatus in the treatment of flexion contractures in the interphalangeal joints]. AB - The use of a Volkov-Oganesjan distraction reposition apparatus in the treatment of flexion contractures of interphalangeal joints gives very satisfactory results. As compared with formerly used methods of conservative treatment, the apparatus makes reposition of the contractures possible, by its design it protects articular cartilages against damage by pressure and makes continuous rehabilitation of the joint possible throughout the period when the apparatus is used. PMID- 1594997 TI - [Acute injuries of knee joint ligaments and their treatment in a type I hospital]. AB - Based on an analysis of the biomechanics of the knee joint the author provides evidence of the importance of its ligaments not only as a passive stabilizer but mainly the irreplaceable function in the cinematic chain due to the ample propriception of ligaments. He emphasizes the necessity to preserve or restore the isometricity of ligaments as the basic prerequisite for smooth and fully coordinated movement. The author presents experience with the diagnosis and surgical treatment of these injuries in their department of a type 1 hospital with policlinic. He provides evidence of the necessity of an active approach and early solution of acutely developed instabilities in surgical and traumatological departments of type 1 and 2 of hospitals with policlinics with regard to previously proved poorer results of delayed operations of acute and unsatisfactory therapeutic results of chronic instabilities. PMID- 1594998 TI - [Present possibilities of surgical treatment in splenic injuries]. AB - Surgical treatment of the spleen has changed fundamentally in recent years- Splenectomy is indicated unequivocally only in systemic diseases. Isolated lienal disease is treated by partial or segmental resection. Ruptures of the healthy spleen caused by injury with minor haemorrhage are treated conservatively with permanent clinical monitoring, laboratory control, control by CT, scintigraphy, angiography and sonography. Conservative treatment is suitable only in isolated lienal injury with the patient in a stable haemodynamic state. The diagnosis can be made accurate by abdominal puncture or peritoneal lavage. Persisting haemorrhage suggesting major injury of the parenchyma must be resolved by urgent laparotomy. After evaluation of the type of injury it is necessary to select treatment which preserves a maximum of lienal tissue. In addition to conventional procedures physical methods of treatment are enforced to an increasing extent. Infra red, hot air, microwave and laser coagulation that the department possesses equipment uncommon in this country equipment which is not easy to obtain. Among modern highly effective methods tissue glues should be mentioned made from highly concentrated fibrinogen and thrombin. Using this method it is possible to treat even deep injuries of the lienal parenchyma as well as tissue after partial or segmental resection. Fibrin glue can be combined with other conventional and physical therapeutic methods. At present the surgeon is faced in case of an injured spleen with the unequivocal task to preserve the spleen, if at all possible. In case the spleen has to be removed because of a major injury its replantation should be ensured; in children orthotopic, in adults heterotopic transplantation into the omentum. By complete removal of a spleen which can be treated and preserved the patient is damaged and exposed to the risk of possible complications threatening the patient's health and possible his life. PMID- 1594999 TI - [Use of autologous veins and streptokinase in vascular complications after replantation of the right forearm]. AB - The authors present the case-history of a 20-year-old worker with an amputation of the forearm in the distal third. After shortening of the bone by 2.5 cm and osteosynthesis by means of grooved splints the blood vessels of the forearm were reconstructed by means of three autoveins. After 12 hours venous and arterial thrombosis developed. During reoperation the thrombotic portions of the vessels were resected and were again reconstructed by means of new autovenous grafts. Streptokinase was instilled into the amputate via the ulnar artery. During the subsequent postoperative period no serious vascular complications developed. Lymphorrhea persisted for some two weeks. To achieve satisfactory function of the hand a corrective operation will be necessary. PMID- 1595000 TI - [Humanistic pseudojustice or pseudohumanistic injustice?]. PMID- 1595001 TI - [Soil on which originality grows]. PMID- 1595002 TI - [Clinical study of systemic juvenile rheumatoid arthritis (Still)]. AB - Thirty-seven patients with systemic JRA were analyzed. Fifty four per cent of patients had mono-cyclic systemic type. Age at onset ranged from 6.0-6.8 years (median 6.4). Boys were more affected than girls (24/11). Cardiac involvement occurred in 10 patients (27%). Patients with cardiac troubles showed significantly much number of the white blood cell counts at admission and the max white blood cell count than those without cardiac troubles. Duration of positive CRP was shorter in patients with cardiac involvement who were all given cortico steroid hormone those without cardiac involvement. This means that it is better to use steroid hormone early for patients with cardiac involvement. Patients with chronic arthritis type had higher elevated erythrocyte sedimentation rate and serum C3 level at admission and longer duration of positive CRP. We speculated that these date showed inflammation of joints. The onset subtype, which was determined by manifestations during the first 6 months of disease, was important for predicting clinical course and outcome. PMID- 1595003 TI - [Analysis of blood coagulation and fibrinolysis in rheumatoid arthritis using the urokinase activated thromboelastography]. AB - The urokinase activated thromboelastography is useful for the analysis of blood coagulation and fibrinolysis in rheumatoid arthritis (RA). In 43 RA patients without extraarticular symptoms (mean year old +/- SD = 50.3 +/- 10.9) and 20 healthy control subjects (mean year old +/- SD = 49.5 +/- 13.8, which is not significant), we have examined reaction time (r), coagulation time (k), r+k, maximal amplitude (ma), lysis time (LT) of the urokinase (final density = 85U/ml) activated platelet rich plasma thromboelastography. In RA patients r, k, r+k are shorter, ma is larger, LT is longer than in control subjects. Especially, k, ma and LT are remarkably statistically significant. these findings suggest that most of RA patients have hypercoagulability and/or prolongation of lysis time simultaneously, k, ma and LT are pathophysiologically important. PMID- 1595004 TI - [Evaluation of immunosuppressive acid protein (IAP) in patients with rheumatoid arthritis]. AB - Immunosuppressive acidic protein (IAP) is evaluated to be a useful parameter for the observation of the clinical course of patients with cancer, who are frequently associated with an increment of serum IAP levels. And also, immune complex diseases such as rheumatoid arthritis (RA), SLE and so on, have been described to produce immune-complex and, consequently, to generate IAP in vivo. Our study focuses on correlations of the IAP values with acute phase reactants, chronic phase reactants and grading of bone stages in patients with RA. Serum IAP showed the positive relationships with grading of bone stages, erythrocyte sedimentation rate (ESR), CRP, RF, RAHA, beta 2-microglobulin (BMG) and IgA in RA. Serum IAP was influenced by deterioration of bone pathological change. The more progressed pathological change of bone, the more increased serum IAP levels. It seems likely that there exist the similar mechanisms with production of IAP and parts of acute and chronic phase reactants and also, serum IAP level may be a useful parameter to predict bone pathological change in patients with RA. PMID- 1595005 TI - [Lung injury associated with bucillamine therapy]. AB - We have reported previously a first case of interstitial pneumonitis in rheumatoid arthritis treated with bucillamine in 1989. Thereafter, a dozen cases with lung injury associated with bucillamine therapy have been reported. To explore the similarities among these patients, we tried to carry out a survey concerning the lung injuries in these cases in the present study. We obtained the following results. (1) Patients with lung injury consisted of 7 females and 3 males, aged 65 years on average (59-72). (2) The total amount of bucillamine used was 20-40 g on average (5.1-144 g) during approximately 100 days. (3) Serum rheumatoid factor was positive in 9 of 10 cases. (4) HLA-DR4 was significantly (p less than 0.01) detected in all cases of lung injury associated with bucillamine. (5) Interestingly the effect of bucillamine on rheumatoid disease activity was excellent in most cases. (6) Drug lymphocyte stimulation test (DLST) using bucillamine was performed in 6 cases. Positive DLST was found in 3 of 6 cases. These results suggest that cell-mediated hypersensitivity reaction (Coombs & Gell type IV) may contribute to the development of lung injury associated with bucillamine therapy. PMID- 1595006 TI - [A case of dermatomyositis associated with thymic abnormalities]. AB - A case of dermatomyositis (DM) associated with thymic cyst with lymphoid follicle formations has been reported. A 57-year-old man developed polyarthralgia, muscle weakness, heliotrope rash and Gottron's sign. Laboratory findings showed elevated values of creatine-phosphokinase, aldolase and transaminase. He was diagnosed as DM and was treated with prednisolone 50 mg/day. Muscle weakness was improved immediately, although rash persisted unchangeably. He was examined for coexistence of malignant tumor which had been reported frequently as associated with DM. Enlargement of thymus was found by computer tomography and then thymectomy was performed. In his thymus, lymphoid follicle formations, which are as often encountered in other autoimmune diseases, were found. So far, the beneficial effect of thymectomy on the improvement of immunological abnormalities not only in patients with myasthenia gravis but also in patients with other autoimmune diseases has been recognized. In this case, intractable rash in DM improved after thymectomy. Further study needs to clarify the relationships between DM and thymic abnormalities. PMID- 1595007 TI - [Ulnar nerve palsy in a RA patient after total knee replacement: a case report]. AB - A 49-year-old housewife had suffered from classical seropositive rheumatoid arthritis for 24 years. The shoulders and hands were involved but the most severs pain and deformity were in both elbows and knees. Consequently, she was unable to sit on wheel chair and was confined to a bed. And then, she was admitted to the Chiba Rehabilitation Center in September, 1986 for bilateral total knee replacement. In April 1987, she had an operation upon the right knee and in June, she had an operation upon the left knee. About 6 weeks after surgery, she felt numbness in bilateral hands. The diagnosis was cubital tunnel syndrome. This was confirmed by electromyographic studies. Surgical release was undertaken without delay. The day following operation the patient remarked on the absence of numbness in bilateral hands. PMID- 1595008 TI - [A case of antiphospholipid syndrome associated with left subclavian artery thrombosis and left external iliac vein thrombosis]. AB - Arterial thrombosis is one of the major symptoms of antiphospholipid syndrome (APS). However, thrombosis in a primary branch of the aorta has rarely been reported in APS. We report here a case of APS complicated by thromboses in both the left subclavian artery and the left external iliac vein. A 32-year-old woman was admitted in May, 1990 complaining of no pulse in the left superficial arteries (e.g., left radial artery) for the past 5 years and acute swelling of the left lower extremity. A left ascending phlebography showed an occlusion of the external iliac vein and arteriography revealed obstruction in the left subclavian artery. Collateral circulations were developed at the site of each thrombus. Clotting and immunological studies revealed a prolonged APTT, a high titer of anticardiolipin antibody and lupus anticoagulant positive. We ruled out various diseases and clinical risk factors predisposing to both arterial and venous thromboses. Accordingly, we concluded that both thromboses were based on APS. Following treatment with anticoagulants, aspirin and corticosteroid, the swelling of her left thigh was diminished and the antibody titer was decreased within 3 months. PMID- 1595009 TI - [An autopsy case of untreated systemic lupus erythematosus with death from acute pulmonary hemorrhage]. AB - An autopsy case of SLE died from acute and diffuse pulmonary hemorrhage is presented. A 50 year-old woman with SLE was admitted to our hospital because of high fever, butterfly rash, discoid skin lesions and renal dysfunction. She died from acute respiratory failure before initiation of the therapy with corticosteroid. Autopsy findings revealed a massive acute intrapulmonary hemorrhage. Histological study demonstrated a pulmonary arterial vasculitis with prominent fibrinoid necrosis at muscular pulmonary artery. No remarkable deposit of immunoglobulins and complements was found within the alveolar walls and pulmonary vessels by immunofluorescence and electron microscopy. Renal histology revealed diffuse proliferative glomerulonephritis with fibrinoid necrosis, crescent formation and wireloop lesions compatible with type IVb according to the WHO classification. The granular deposit of IgM, C3 and Clq, and electron dense deposit was found by immunofluorescence and by electron microscopy, respectively, in the kidney. The small arteries and veins in other organs, such as liver, spleen, bladder, ovary and rectum also revealed fibrinoid vasculitis. Acute infectious lesion was not observed in any tissue examined. The diffuse pulmonary hemorrhage in SLE could be one of the manifestations of active and severe systemic vasculitis. PMID- 1595010 TI - [Current topics of osteoporosis]. PMID- 1595011 TI - Gonococcal infection of the newborn in Florida, 1984-1989. AB - An increase in neonatal gonococcal infections was recorded in Florida between 1984 and 1988. By reviewing Florida sexually transmitted disease surveillance case records between 1984 and 1989, 68 cases of neonatal gonococcal infections were identified state-wide. Those 68 cases included 55 (81%) cases of gonococcal ophthalmia neonatorum, 4 genital infections, 1 nasal infection, 1 ear infection, 1 skin infection, and 1 scalp infection. At birth, positive culture results were demonstrated in 3 gastric and 2 respiratory aspirate cultures. A case-control study using birth certificates as the source of information showed that mothers of infected infants were more likely to be younger, black (odds ratio [OR] = 6.2; 95% confidence interval [CI] 2.3, 16.2), and less educated (less than a high school education, OR = 2.9, CI 1.0,8.8) in comparison to mothers of control subjects. Although mothers of infected newborns were less likely to have received prenatal care than were mothers of control subjects, this difference was not statistically significant. Maternal substance abuse was documented among 19% of the mothers of the infected infants. The rate of clinical gonococcal ophthalmia neonatorum in Florida hospitals from which cases had been reported was 1.7 per 10,000 live births, and tended to be higher in hospitals using erythromycin than in hospitals using any other prophylactic eye treatment. This study suggests that the rate of neonatal gonococcal infection, in particular ophthalmia neonatorum, may have increased in Florida among high-risk populations between 1984 and 1988, and underscores the need for targeted prevention efforts and surveillance. PMID- 1595012 TI - Crack use and human immunodeficiency virus infection among San Francisco intravenous drug users. AB - The relationship between crack use, human immunodeficiency virus (HIV) infection, and risk behavior among 1281 intravenous drug users in treatment is analyzed. Of these patients, 23% reported crack use, and blacks and women were more likely to use crack. Of crack users 19% were HIV positive, in comparison to 8% of non-users (OR = 2.9, P = 0.0001). In multivariate analysis, the association was no longer significant (OR = 1.4, P = 0.14). Independent behavioral predictors of HIV seropositivity were number of sexual partners, and intravenous cocaine use among blacks. Crack use was a marker for high-risk sexual and drug use behavior in the study population. PMID- 1595013 TI - Prevalence of human immunodeficiency virus in the patient population of a sexually transmitted disease clinic. Association with syphilis and gonorrhea. AB - An unlinked seroprevalence survey of human immunodeficiency virus (HIV) antibody was conducted using stored sera from all patients who attended the sexually transmitted disease (STD) clinic in Halifax, Nova Scotia between 1980 and 1986. None of the sera collected from 584 patients during 1980 were HIV positive. Of the 2867 patients who visited the clinic between 1981 and 1986, 27 (0.9%; 95% CI 0.6% to 1.2%) had the antibody. None of the 784 female patients were HIV seropositive. Of the 1,884 heterosexual men in the study, 5 (0.3%; 95% CI 0.1% to 0.5%) were HIV seropositive, and 22 (11.1%; 95% CI 6.7% to 15.5%) of the 199 homosexual men were HIV seropositive. There was a strong association between a history of syphilis and HIV antibody among heterosexual men (OR = 76.8; 95% CI 12.0 to 491.3; P = 0.001). Among homosexual men younger than 30 years of age, HIV infection was associated with a history of syphilis (OR = 18.2; 95% CI 5.1 to 64.7; P = 0.035) and a history of gonorrhea (OR = 8.2; 95% CI 4.2 to 16.0; P = 0.001). The association between a history of gonorrhea and HIV infection was strongest among homosexual men who had three or more sexual partners in the last month. These findings supplement existing evidence that STDs increase the likelihood of HIV transmission. PMID- 1595014 TI - Grants awarded to establish five Sexually Transmitted Disease Cooperative Research Centers. PMID- 1595015 TI - Epidemiological synergy. Interrelationships between human immunodeficiency virus infection and other sexually transmitted diseases. AB - Understanding the role of other sexually transmitted diseases (STDs) in the transmission of human immunodeficiency virus (HIV), the role of STDs in progression of HIV disease, and the role of HIV infection in alterations of natural history, diagnosis, or response to therapy of STDs is critical to the development of optimal strategies for HIV control. One hundred sixty-three studies on the interrelationships between HIV infection and other STDs were examined. Of 75 studies on the role of STDs in HIV transmission, the 15 analyses of examination or laboratory evidence of STDs adjusted for sexual behavior showed that both ulcerative and nonulcerative STDs increase the risk of HIV transmission approximately 3- to 5-fold. Due to limited data, the role of STDs in progression of disease remains unclear. Preliminary data from 83 reports on the impact of HIV infection on STDs suggest that, at a community level, HIV infection may increase the prevalence of some STDs (e.g., genital ulcers). If coinfection with HIV prolongs or augments the infectiousness of individuals with STDs, and if the same STDs facilitate transmission of HIV, these infections may greatly amplify one another. This "epidemiological synergy" may be responsible for the explosive growth of the HIV pandemic in some populations. Effective STD control programs will be essential to HIV prevention in these communities. PMID- 1595016 TI - Evaluation of a direct fluorescence assay as a screening method in asymptomatic young women. AB - The purpose of the study was to evaluate one rapid antigen test (DFA), in comparison to culture, for the detection of Chlamydia trachomatis in young, asymptomatic women. C. trachomatis was isolated from specimens of 8.6% of the patients studied, and 11.3% had 10 or more elementary bodies (EBs) in their specimens. A lowered cut-off point of the DFA did not affect the sensitivity of the method, but the predictive value of a positive test decreased markedly when the cut-off point was lowered. Patients with symptoms of genital infection, signs of genital infection, or both had a higher DFA sensitivity than those who were asymptomatic. Patients whose specimens yielded 1-9 EBs were reexamined three times, once every fourth week. We found little evidence that those patients should be regarded as falsely negative in culture, since most of them remained negative. In order to minimize the social consequences of a false positive test, the DFA method should not be substituted for culture as a diagnostic tool, especially for screening of asymptomatic groups with a low prevalence of C. trachomatis. PMID- 1595017 TI - Disease prevalence among women attending a sexually transmitted disease clinic varies with reason for visit. AB - Prevalence of sexually transmitted diseases (STD) and selected behavioral and demographic variables were evaluated in 279 women attending a Baltimore STD clinic, using a standardized questionnaire and cultures for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis. Stratified by reason for clinic visit, 102 (37%) of 279 women attending the clinic stated that they were recent contacts to men with STDs with the majority (59 out of 102, or 58%) reporting gonorrhea contact as their reason for visit. Another 124 women (44%) came to the clinic for symptom evaluation, and 53 (19%) for other reasons. Prevalence of STDs was higher among those attending as contacts than among noncontacts: 35% versus 15% for N. gonorrhoeae; 26% versus 16% for C. trachomatis; and 27% versus 15% for T. vaginalis (P less than 0.05 for each). Furthermore, multiple infections were found in 23% of those attending as contacts but only in 10% of noncontacts (P less than 0.001). In general, patients reporting contact with an infected person were also less likely to report symptoms (43% versus 34%, P less than 0.001), despite increased disease prevalence. These data suggest that multiple STDs are often present in women attending STD clinics, irrespective of reason for visit. Merely treating women for reported exposure without further evaluation will fail to identify a substantial number of women coinfected with other organisms. PMID- 1595018 TI - Cefixime in the treatment of uncomplicated gonorrhea. AB - One hundred consecutive patients with uncomplicated gonorrhea were treated with 800 mg of cefixime. Follow-up evaluation was obtained for 73 patients, and at that time 71 of the 73 had negative culture results for Neisseria gonorrhoeae. Minimal adverse side effects were reported. Cefixime 800 mg appears to be an excellent treatment for uncomplicated gonorrhea. PMID- 1595019 TI - Evaluation of field follow-up in a sexually transmitted disease clinic for patients at risk for infection with Neisseria gonorrhoeae and Chlamydia trachomatis. AB - Field follow-up to locate and treat partners of patients with syphilis and gonorrhea is standard procedure in the United States. The present study utilized 12,732 heterosexual index patients with gonococcal infection, chlamydial infection, and related syndromes to evaluate the effectiveness of field follow-up over a 6-year period. Field follow-up located 82% of the 13,845 partners identified by the index patients. Of those partners who were located, 36% had a documented infection with either chlamydia or gonorrhea. An average of only 1.09 partners per index patient was named, however, indicating that all partners may not have been reported. The largest number of infected partners was located for all index patients with gonorrhea and for men with chlamydia. Contact tracing was also effective for women with chlamydia, although less so. Field follow-up, as conducted in this study, is effective in locating the partners who are reported by the index patients. PMID- 1595020 TI - Portosystemic shunt versus orthotopic liver transplantation for the Budd-Chiari syndrome. AB - We have analyzed the indications and results of shunt operation versus orthotopic liver transplantation (OLT) in 22 patients with Budd-Chiari syndrome (BCS). The underlying cause of the syndrome was similar between the two groups and was related to myeloproliferative disorders or the use of birth control pills in 18 of 22 patients. The results of biopsies of the liver showed centrilobular congestion and necrosis in all candidates who underwent shunting and the presence of fibrosis and cirrhosis in the OLT candidates. The indications for shunts included symptoms related to portal hypertension only and well-preserved synthetic hepatic function. Ten patients were treated with 12 shunt procedures, including mesoatrial (eight patients) and side to side portacaval shunt (four patients). Significant complications after shunt procedure included fulminant (one of ten patients) and progressive (one of ten patients) hepatic failure requiring urgent OLT; one death occurred because of pulmonary sepsis. Indications for OLT were signs of end stage liver expressed by severe portal hypertension and variceal bleeding (four of 14 patients), progressive encephalopathy (seven of 14 patients) and poor synthetic function (bilirubin greater than 3 milligrams per deciliter in eight of 14 patients and albumin less than 3.0 grams per liter, or both, in ten of 14 patients). Fourteen patients were treated with 16 OLT, three patients had retransplantation for primary nonfunction graft (two of 14 patients) or chronic rejection (one of 14 patients). There were two early deaths in the group. With a follow-up period between two months to five years, 12 of 14 patients undergoing OLT are alive, fully functional and have normal liver function tests. Seven of ten patients who had shunts are alive, six are able to maintain normal activity and one has progressive end stage hepatic disease and is not a candidate for OLT. However, the hepatic function continues progressively to be abnormal. Various options are available for the treatment of the syndrome. Portosystemic decompression is effective and should be considered at the early stage of the disease, prior to the development of significant hepatic failure. However, few of the patients will continue to have slow, but progressive hepatic failure and may require OLT. The only effective treatment for end stage hepatic disease secondary to the BCS is OLT. PMID- 1595021 TI - The preperitoneal approach in the repair of recurrent inguinal hernias. AB - Preperitoneal repair of 98 recurrent inguinal hernias performed at our teaching hospital was studied. In 55 instances, primary closure was performed and in 43 hernias, mesh prosthesis was applied. Rerecurrence was seen after 32 corrections (a follow-up examination period of 45 months). Nine asymptomatic recurrences were found. Unilateral versus bilateral repair showed a 27 and 50 per cent recurrence rate, respectively (p = 0.037). Results after primary closure and after mesh application were similar, and no correlation with the number of recurrences, age or presence of causes of raised abdominal pressure was observed. In 20 reoperations performed after the follow-up date, ten lateral hernias were found, indicating technical failure as a possible cause of rerecurrence. A high rate of recurrence after preperitoneal approach for recurrent inguinal hernia may be explained by technical shortcomings and detection of a high percentage of asymptomatic recurrences at physical examination. PMID- 1595022 TI - Cholecystectomy during pregnancy without fetal loss. AB - Cholecystectomy in the pregnant patient has been generally avoided because of the reported high incidence of associated fetal loss that has been linked to spontaneous and elective abortion during the first trimester and premature labor during the third trimester. Recent developments relating to diagnostic and anesthetic management and the use of tocolytic agents have altered the over-all approach to patients. We have, therefore, retrospectively reviewed the medical records of all women discharged from four area hospitals during 1982 to 1987 with a concurrent diagnosis of cholelithiasis and pregnancy. Twenty-two patients met the review criteria. The incidence of biliary stone disease among gravid patients during the time interval was 0.05 per cent. Of 22 patients, none underwent radiation for diagnosis. Nine patients underwent cholecystectomy while pregnant; two were operated upon during the first trimester, four during the second and three during the third. Three required common bile duct exploration and three had intraoperative cholangiograms. Elective abortion was not recommended to the six patients because of radiation exposure. Two of nine had premature contractions develop that were controlled with tocolytic agents. There were no spontaneous abortions. The mean Apgar scores for neonates born subsequent to cholecystectomy was virtually identical to neonates born to patients in whom cholecystectomy was deferred. It is concluded that the diagnosis and surgical treatment of cholelithiasis can be safely undertaken in the pregnant patient without fetal loss. Delaying appropriate surgical therapy no longer seems warranted. PMID- 1595023 TI - Intraoperative sonography during cholecystectomy for gallstones. AB - The current study reports on the ease and results of intraoperative sonography in 131 patients operated upon for gallstones. Sonography was performed through a standard incision or a small incision, without duodenal mobilization and prior to systematic cholangiography. Sonography or cholangiography, or both, detected biliary duct stones in eight patients. The entire biliary tract was visualized by ultrasound in 123 patients. Sonography identified seven patients with stones in the major biliary ducts and overlooked only a single stone of the cystic duct. In contrast, intraoperative cholangiography failed to reveal stones in a right hepatic duct and led, in another instance, to unnecessary choledochotomy. During cholecystectomy for gallstones, sonography is a simple efficient technique providing good detection of biliary stones. It is the study of choice and cholangiography is required in only selected instances in which sonographic visualization is incomplete. There may be future value in sonographic applications for laparoscopic cholecystectomy. PMID- 1595024 TI - Surgical treatment of symptomatic giant hemangiomas of the liver. AB - Cavernous hemangiomas are the most common benign tumors of the liver. Twenty-four patients who had hepatic resections for giant symptomatic hepatic hemangiomas during a six year period at a single institute were retrospectively reviewed to analyze indications for surgical treatment and evaluate operative mortality and morbidity. There were 18 women and six men varying in age from 41 to 69 years with an average age of 52.5 years. Moderate to severe pain, discomfort, feeling of fullness, bloating and sensation of an abdominal mass were the most commonly reported symptoms. Ten patients had moderate anemia and two had severe anemia. Tumors were visualized by ultrasonography in all patients and by computed tomography in 18. Angiography was performed in all patients with diagnostic confirmation of a benign hemangioma in all but one patient in whom an angiosarcoma was suspected. The resection was feasible in each patient: 20 minor hepatic resections (three wedge, 11 segmentectomies, six bisegmentectomies) and four right hepatic lobectomies were carried out. There were no surgical deaths. Two patients had postoperative complications: one patient had a pneumonia on the right side and one had wound infection. The benign nature of the tumors was confirmed in all. The lesions varied in size from 5.6 to 26 centimeters in diameter. Symptoms and hematologic disorders were relieved in all patients in the follow-up. The results of our experience confirm that resection for giant symptomatic hepatic hemangioma represents a safe radical curative procedure. Medical treatment is justified in smaller lesions or in asymptomatic patients. PMID- 1595025 TI - The value of operative ultrasonography in diagnosing tumor extension of carcinoma of the stomach. AB - Operative ultrasonography was performed during operations to improve the accuracy of diagnosing the extent of the spread of carcinoma of the stomach in the following areas: tumor invasion in the gastric wall (31 patients), para-aortic lymph node metastasis (30 patients) and hepatic metastasis (30 patients). The over-all diagnostic accuracy rates of operative ultrasonography were 81 per cent for determining the depth of tumor invasion, 80 per cent for carcinoma of the mucosa, 70 per cent for carcinoma of the submucosa, 83 per cent for carcinoma of the proper muscle, 80 per cent for carcinoma of the subserosa and 100 per cent for carcinoma of the extraserosa. The over-all accuracy of operative ultrasonography in diagnosing para-aortic lymph node metastasis was 93 per cent. In comparison with the results of preoperative studies, the accuracy (sensitivity) of operative ultrasonography was significantly superior in diagnosing metastasis to the lymph nodes. In three of 30 operations, preoperatively unrecognized and nonpalpable (occult) hepatic metastases were identified by operative ultrasonography. Operative ultrasonography provides more accurate information regarding the spread of carcinoma of the stomach, and thus may be helpful in deciding upon the type of surgical procedure or in avoiding unnecessary tissue dissection. PMID- 1595026 TI - Long term success of aortoiliac operation for arteriosclerotic obstructive disease. AB - The current retrospective study was performed on 747 patients with aortoiliac obstructive disease who underwent reconstructive operation. Unlike many other centers, the University Hospital Leiden has, throughout the years, maintained the strategy of avoiding the implantation of a prosthesis in patients with limited and localized obstructive disease that could readily be treated with an endarterectomy. When a prosthesis was used, it was anastomosed to the femoral artery if a more proximal anastomosis was not feasible. In the present study, the long term outcome of the strategy is evaluated. Three groups of patients were studied--245 patients with moderate claudication, 331 patients with severe claudication and 162 patients with critical ischemia at presentation. Thromboendarterectomies were used in 229 patients (30.7 per cent) and prosthetic reconstructions in 518 patients (69.3 per cent), of which 339 (45.5 per cent) were aortoiliac reconstructions. The perioperative mortality rates were 1.6, 3.0 and 3.1 per cent for the three groups, respectively. Atherosclerotic heart disease was the most common cause of perioperative (30.0 per cent) and late (30.8 per cent) death. Late complications of surgical treatment also contributed significantly to the causes of late deaths (12.1 per cent). Because over-all survival rates in the current series compared favorably with those in other series, the influence of reconstructive operation on late survival was compensated for by a beneficial effect in patients without such complications. Secondary operations for late complications, such as false aneurysms and aortoiliac reobstruction or for progressive obstructive disease, were necessary in 21 per cent of all 727 survivors of the first operation. Actuarial curves with various endpoints--mortality, secondary operation, patency of aortoiliac segments, functional failure, amputation, presence of mild, moderate and severe claudication--were calculated according to the standard method of life table construction. In terms of technical success rates, the results of our surgical technique strategy compared favorably with those reported in other series, in which most patients were treated with aortobifemoral prostheses. The chances of functional failure increased with time, amounting to about 23 per cent at 15 years postoperatively for each group of patients. Comparison of technical and functional success rates showed a significant disparity, which was explained by the effects of collateral blood flow in instances of aortoiliac reobstruction and of progressing femoropopliteal obstructions in instances of open aortoiliac vessels. PMID- 1595027 TI - Management of chylothorax complicating extensive esophageal resection. AB - Between January 1983 and May 1987, 255 esophagectomies were performed for carcinoma of the middle (40 patients) or lower (215 patients) esophagus. All patients were operated upon through a left thoracolaparotomy and underwent a radical en bloc resection of the tumor along with all palpable mediastinal nodes. Ten patients had chylothorax develop postoperatively. There were seven men and three women with a mean age of 65.7 years (range of 37.0 to 81.0 years). Parameters that were statistically evaluated for possible correlation to increased incidence of chylous fistula were age, sex, site and size of tumor, histologic type, mediastinal lymphatic involvement and elective prophylactic ligation of the major thoracic duct (MTD) at the conclusion of the procedure. It was found that elective ligation of the MTD was associated with a lower occurrence of chylothorax (2.1 per cent) as compared with those with no routine ligation (9 per cent), p less than 0.05. The leak was successfully treated by repeated thoracotomy and mass ligation of the MTD in eight patients, while one patient underwent closed tube thoracostomy. In one instance, only a pleuroperitoneal shunt was performed. The over-all hospital mortality rate from chylothorax was 10 per cent and there was a late death because of pneumonia. We recommend prophylactic ligation of the MTD in all instances of extensive esophageal resection for the prevention of chylothorax, as well as early thoracotomy for the management of established leaks. PMID- 1595028 TI - Prospective evaluation of the contraction stress and nonstress tests in the management of post-term pregnancy. AB - Eight hundred and nineteen patients were evaluated at greater than or equal to 280 days' gestation. All patients underwent nonstress test (NST) and breast stimulation to induce contraction stress test (CST), except where contraindicated. If CST was nonqualifying (less than three contractions per ten minutes), Pitocin (oxytocin) was used to complete the CST if there was a nonreactive NST. Delivery was instituted for any abnormal CST, even with a reactive NST, based on the last test within seven days of delivery. There were 747 reactive NST and 72 nonreactive NST. Breast stimulation for CST was done in 655 instances--315 (48 per cent) had nonqualifying CST and 340 (52 per cent) had qualifying CST. There was an increased incidence of induction in the nonqualifying CST group and abnormal CST group. There were no statistically significant differences in perinatal outcomes in the group with reactive NST, irrespective of the CST result. There were no antepartum fetal deaths. PMID- 1595029 TI - Multivariate analysis of morbidity and mortality from the initial surgical management of obstructing carcinoma of the colon. AB - Eighty consecutive patients presenting with complete large intestinal obstruction from primary carcinoma were evaluated. A multivariate analysis was performed to evaluate perioperative morbidity and mortality. There were five deaths in the immediate postoperative period (30 days). Extensive and lesser complications occurred in eight and 11 patients, respectively. There were 25 lesions of the right colon, whereas in 55 patients, the lesion was located distal to the left branch of the middle colic artery. Females were more likely to present with obstructed carcinomas of the left colon than males. Patients with an obstruction of the left colon more frequently presented with dehydration than those with a tumor of the right colon (p less than 0.05). Most carcinomas of the right colon were resected, whereas lesions of the left colon were managed with diverting colostomy in 33 patients and by primary resection in 22. Thirteen patients with carcinomas of the left colon had an immediate anastomosis without mortality. Preoperative severe cardiopulmonary disease, Acute Physiology and Chronic Health Evaluation score and advanced carcinoma (Dukes' C or D) were statistically related to early hospital morbidity and mortality, while individual physiologic parameters, site of lesion or operation performed were not. Primary resection may be performed safely in selected patients. Multivariate assessment and clinical staging may allow for appropriate patient selection and improve immediate outcome. PMID- 1595030 TI - A technique to simplify insertion of the Bird's Nest cava filter from the left femoral vein. PMID- 1595031 TI - Preparation of small caliber intestine for anastomosis with the EEA stapler. PMID- 1595032 TI - The life and contributions of Doctor George Nicholas Papanicolaou. PMID- 1595033 TI - The relevance of tumor draining lymph nodes in cancer. AB - Involvement of RLN by tumor cells is a prognostic index of survival and a biologic indicator of more distant metastatic disease. In most solid tumors in humans, removing the draining lymph nodes seems to have little impact on survival, although it may be important in local control of disease. Although data from animal studies suggest that tumor draining RLN may have an important antitumor role (particularly in the early stage of tumor growth), there is a shortage of evidence in humans to substantiate such a supposition. At the time of operation, alterations in nodal microarchitecture with an expansion of T and B lymphocyte compartments is well documented. The findings of immunologic studies, however, reveal a general hyporeactivity, inappropriate humoral and cell mediated responses to antigens associated with tumors and a low or absent natural cytotoxicity. Failure of host defenses, possibly induced by tumors, may be responsible for progressive growth of tumor and spread of tumor to the RLN, resulting in dissemination of the tumor cells, establishment of metastatic deposits and concurrent growth of tumor in lymph nodes. Regional lymphatics may have an important antitumor role at the early stage of the development of a tumor (as yet unproved in humans). With progressive growth of tumor, the lymphatics are unlikely to be beneficial, not only because of a failure of nodal anticancer defenses, but because they provide a possible preferred biologic environment for tumor cell proliferation and an anatomic route for dissemination to distant tissues and organs. PMID- 1595034 TI - Intracranial pressure monitoring: fiberoptic monitor compared with the ventricular catheter. AB - Among the frequently utilized intracranial pressure (ICP) monitoring devices employed in neurosurgical practice is the Camino fiberoptic monitor. Several recent studies have described results with the Camino monitor and compared it with other forms of ICP monitoring with varying results and conclusions. The aim of this study was to compare simultaneous ICP readings from the Camino fiberoptic monitor placed in the brain parenchyma and from a ventricular catheter. ICP values were recorded for up to 118 hours in 10 patients. It was determined that the Camino ICP measurements exceeded those of a ventricular catheter in 66% of total measurements for the 10 patients. The mean ICP difference between the Camino fiberoptic system and the ventricular catheter was 9.2 +/- 7.8 mm Hg. This result suggests that the correlation between intraparenchymal pressure measured by the Camino fiberoptic monitor and the intraventricular pressure is not as close as previously described. PMID- 1595035 TI - Effects of nilvadipine on neuronal function in the ischemic cat brain. AB - The effect of nilvadipine, a dihydropyridine-type calcium entry blocker, on neuronal function during and following ischemia was investigated with a model of focal cerebral ischemia in cats and was compared with that of nicardipine. Drugs were given intravenously 30 minutes before occlusion of the left middle cerebral artery (MCA). Occlusion of the left MCA for 60 minutes was followed by reperfusion for 90 minutes. The amplitude of the somatosensory evoked potentials (SEPs), and the residual relative regional cortical blood flow in the left ectosylvian gyrus and the left posterior sigmoid gyrus, were higher or had a tendency toward higher values in the nilvadipine-treated (32 micrograms/kg) group than in other groups. After reperfusion, the amplitude of SEPs rapidly recovered in the nilvadipine-treated groups. When administered before MCA occlusion, nilvadipine improved neuronal function measured by SEPs both during and following the ischemic period. Thus, nilvadipine is effective against neuronal dysfunction in focal cerebral ischemia. PMID- 1595036 TI - Effect of temporary pacing on patients with bradycardia in the acute stage following subarachnoid hemorrhage. AB - In nine cases of bradycardiac arrhythmia of less than 50 bpm that arose during cerebral vasospasm following aneurysmal rupture the patients were treated by temporary pacing. In patients with cerebral vasospasm, in whom autoregulation of the cerebral circulation is impaired, bradycardia aggravates the risk of decreased cerebral blood flow. This study demonstrated that temporary pacing is an effective and safe procedure in maintaining heart rate during vasospasm. PMID- 1595037 TI - Effects of endothelial-cell-derived growth factors on cultured astrocytes. AB - To clarify the participation of endothelial-cell-derived growth factors (ECDGFs) in astrocytosis, the effects of endothelial-cell-conditioned medium (ECCM) derived either from normotensive rats or spontaneously hypertensive, stroke-prone rats (SHRSPs) on proliferation of C6 cells of an established rat glioma cell line were bioassayed. The ECCM from both strains stimulated proliferation of astrocytes, but the ECCM from SHRSPs showed a higher mitogenic activity for astrocytes than that from normotensive rats. Growth-promoting activity of the ECCM derived from SHRSPs showed an increase that was linear to the conditioning time. These results seem to indicate that endothelial cells produce and release factors that promote the growth of astrocytes. It seems also probable that chronic hypertension causes an increase in production and release of such ECDGFs that correlated with astrocytic proliferation. PMID- 1595038 TI - Invasiveness in in vitro and clinical evaluation of meningiomas. AB - Fragments of freshly isolated human meningiomas were cultured in vitro to form cell monolayers. These monolayers were confronted with embryonic chick heart fragments in vitro for 1, 2, 4, and 7 days. Microscopically, three different histological patterns were observed. Type I included necrotized meningial cells; type II presented surviving meningial cells; type III included meningial cells that had invaded the host tissue. The clinical analysis included the histopathological diagnosis, the macroscopic situation at surgical intervention, and the follow-up with or without recurrence. Correlation between these clinical parameters and the in vitro results demonstrated that type III confrontations correlated with macroscopic infiltration in the brain parenchyma and tumor recurrence. Invasiveness in vitro was seen in two anaplastic and two transitional meningiomas. PMID- 1595039 TI - Surgical treatment of the spontaneous spinal epidural abscess. AB - Seven cases of spontaneous epidural abscess are reviewed. Three patients had posterior abscesses and no evidence of vertebral body osteomyelitis. These patients had excellent outcomes with laminectomies and antibiotics. Because of significant vertebral destruction, two patients with vertebral osteomyelitis required posterior fixation after laminectomy. Two other patients with vertebral osteomyelitis had complete destruction of the vertebral body and required anterior decompression and fusion in addition to posterior fixation. In the four patients with vertebral osteomyelitis, morbidity was high, reflecting their age and significant medical problems. This review supports the contention that medically stable patients with posterior epidural abscesses can be treated with laminectomy and antibiotics with little risk of progressive instability. The proper surgical treatment of anterior epidural abscesses secondary to osteomyelitis requires knowledge about the amount of destruction of the supporting columns, the amount of neural compression secondary to the purulence, and the patient's general medical condition. PMID- 1595040 TI - Giant basal prolactinoma extending into the nasal cavity. AB - An unusual case of a giant prolactinoma extending to the nasopharynx and nasal cavity is presented. A 35-year-old man admitted for nasal obstruction and visual disturbances was found to have bilateral anosmia, right homonymous hemianopsia, and a right hemiparesis. The serum prolactin level was 13,300 ng/mL. Radiological examination revealed a large mass invading the skull base and extending into the suprasellar region and the left frontal lobe superiorly and into the nasopharynx inferiorly. Subtotal removal was done through a bilateral orbitofrontal craniotomy, which was followed by radiotherapy and bromocriptine administration. Immunohistochemical analysis confirmed a prolactinoma. The rarity of such a tumor, its location and extension, and the usefulness of magnetic resonance imaging and immunohistochemistry are stressed. Pertinent literature is reviewed. PMID- 1595041 TI - Fenestration of the supraclinoid internal carotid artery associated with carotid bifurcation aneurysm. AB - Fenestration of the internal carotid artery is extremely rare. The authors describe a fenestration at the supraclinoid portion of the left internal carotid artery revealed after subarachnoid hemorrhage from an ipsilateral carotid bifurcation aneurysm. This is the third reported case of fenestration of the intracranial internal carotid artery. Fenestrated cerebral vessels and their possible genesis and surgical management are discussed. PMID- 1595042 TI - Hemifacial spasm associated with a cerebellopontine angle arachnoid cyst in a young adult. AB - There are no reported cases of hemifacial spasm associated with an arachnoid cyst in the literature. We report the first case of hemifacial spasm with an ipsilateral cerebellopontine angle arachnoid cyst in a 25-year-old man. The patient underwent evacuation of the arachnoid cyst by a partial membranectomy without any beneficial effect, and finally got rid of the hemifacial spasm by reexploration and microvascular decompression of the facial nerve. The operative findings and results revealed that the cyst produced deviation of the ipsilateral posterior inferior cerebellar artery, which was secondarily in contact with the root exit zone of the facial nerve. PMID- 1595043 TI - Glial cyst of the pineal gland with characteristic computed tomography, magnetic resonance imaging, and pathological findings: report of two cases. AB - Two cases of glial cyst of the pineal gland are documented. Preoperative computed tomography and magnetic resonance imaging revealed cystic lesions of the pineal region with contrast enhancement of the walls, suggesting neoplastic lesions rather than true cysts. However, the histopathological examination of the resected specimens revealed the presence of glial tissue and normal structure of pineal gland and capsule, characteristics that were consistent with those of glial cysts of the pineal gland. Headache and visual disturbance were resolved after total removal of the cysts. PMID- 1595044 TI - Neurosurgeons and ideas before their time. AB - As a complementary inquiry to previous studies on citation analysis in neurosurgery, a group of ideas before their time has been arbitrarily selected by the author from 3792 first-authored papers written between 1897 and 1980 by 50 of the first American neurosurgeons. There were eight neurosurgeons who proposed 12 original theories or procedures whose importance was not recognized at the time of publication. Although the value of these ideas was not initially judged to be significant, these concepts became a part of the intellectual consensus of neurosurgery or related disciplines after varying periods of time. Technical constraints constituted the most important reason for delayed recognition of these innovative and creative ideas. Other factors were an unsuitable medium of communication, fixed scientific attitudes, prestige of previous authors, incomplete literature review by later authors, and a failure to verify observations by other investigators. The question is raised as to whether these factors might continue to affect present and future clinical investigation and laboratory research in neurosurgery. PMID- 1595045 TI - Transaction of the American Neurological Association. The forty-ninth annual meeting of the American Neurological Association, held in Boston, May 31, June 1 and 2, 1923. PMID- 1595046 TI - Acute subfrontal epidural hematoma: report of two cases. AB - Two cases of acute subfrontal epidural hematoma are reported. Both were diagnosed by computed tomography scan and successfully removed via a frontal craniotomy. PMID- 1595047 TI - Long-term results of transplantations to repair median, ulnar, and radial nerve lesions by a microsurgical interfascicular autogenous cable graft technique. AB - A comprehensive analysis of 187 patients (78 median, 86 ulnar, and 23 radial nerve lesions) treated by an interfascicular autogenous nerve grafting technique is presented. After a follow-up of at least 18 months good motor recovery was achieved in 72% of median nerve lesions, 77% of ulnar nerve lesions, and 57% of radial nerve lesions. Good functional sensory recovery was found in 36% of median, 45% of ulnar, and 48% of radial nerve lesions. It appears by multivariate analysis that the results obtained generally were better in younger patients, in patients with a shorter preoperative delay, and in cases with a shorter transplant. PMID- 1595048 TI - Diagnostic accuracy of AIDS-related CNS lesions. AB - Because of the high incidence of neurological complications seen in patients with acquired immunodeficiency syndrome (AIDS), an increasing number of these cases are being referred to neurosurgeons for consideration of intracranial biopsy. To better determine the need for biopsy in these patients we evaluated the accuracy of non-tissue-based neurological diagnoses in AIDS patients who subsequently had a final diagnosis on the basis of biopsy or postmortem brain examinations. The records of 56 AIDS patients who had undergone either autopsy or brain biopsy were retrospectively reviewed. Of the ten patients who underwent biopsy, three were found to have a lesion that was different from the suspected diagnosis and that resulted in a change in treatment. Thirty patients with neurological symptoms had postmortem brain examinations. In the case of the 12 patients who had carried specific diagnoses and received treatments based on those diagnoses, only six diagnoses (50%) were proven correct at autopsy. Of the 18 cases that did not record a specific antemortem diagnosis, in only 5 were normal brains reported, while the others reported a variety of nonspecific or infectious findings. Twelve patients without neurological symptoms had postmortem brain examinations and only six of these (50%) had normal or slightly atrophic brains. Case reports of the others noted nonspecific findings most of which were suggestive of subacute HIV encephalitis. The poor rate of diagnostic accuracy in this series suggests that biopsy should be considered for atypical lesions or those that do not respond to empiric therapy. The use and relative sensitivities of various diagnostic studies are also discussed. PMID- 1595049 TI - Spinal cord infarction caused by cartilage embolus to the anterior spinal artery. AB - Cartilaginous embolization of spinal vessels is a rare cause of spinal cord infarction. A 63-year-old woman developed sudden onset of painful, fatal paraparesis following a valsalva-like maneuver. Autopsy demonstrated recent nonhemorrhagic infarction of the caudal thoracic spinal cord secondary to complete occlusion of the anterior spinal artery by cartilage. The literature pertaining to 28 previously reported cases is briefly reviewed. PMID- 1595050 TI - Spinal cavernous angioma: a rare cause of subarachnoid hemorrhage. AB - A case of cervical intrathecal extramedullary cavernous angioma is presented. The rarity of this lesion in comparison with the more frequent vertebral cavernous angiomas with secondary extension to the epidural space is emphasized. The special features of this case are noted: the acute clinical onset due to recurrent subarachnoid hemorrhages, the visualization only by means of magnetic resonance imaging, and the unusual cervical level. The most debated characteristics of these lesions and the relevant literature are summarized. PMID- 1595051 TI - MRI-documented regression of a herniated cervical nucleus pulposus: a case report. PMID- 1595052 TI - Intracerebral hemorrhage from a middle meningeal arteriovenous fistula with a giant venous varix. AB - A patient with a congenital arteriovenous fistula between the middle meningeal artery and a cortical vein with a giant venous varix is described. The patient presented with an intracerebral hemorrhage that had been evacuated. Permanent cure of the fistula was achieved without morbidity by embolization with Ivalon particles. PMID- 1595053 TI - Lymphocytic hypophysitis: report of a case in a man with cavernous sinus involvement. AB - Lymphocytic hypophysitis (LH) is a rare inflammatory disease of the pituitary that produces hypopituitarism. It more commonly affects women during pregnancy or shortly after childbirth. Of the 34 reported cases only three have been males. We report the fourth known case of lymphocytic hypophysitis in a male who presented with hypopituitarism, diplopia, and cavernous sinus involvement. To our knowledge this is the second report of involvement of the cavernous sinus by LH. A comparative study of all four male cases is also presented. The findings reveal that the mean age at presentation in the male patients is 52.3, nearly 21 years older than that reported for female cases. Impotence with associated decrease in libido is the most common presenting symptom. Extraocular muscle palsy with associated infiltration of the cavernous sinus is an exclusive finding among male patients with LH. Concerning prognosis, none of the male patients regained pituitary function that had been lost at the time of presentation but required chronic replacement therapy. PMID- 1595054 TI - Temporal lobectomy for seizures associated with unilateral schizencephaly. AB - Schizencephaly is characterized by unilateral or bilateral cerebral clefts associated with neurologic deficits and epilepsy. Most commonly schizencephaly is attributed to abnormal neuronal migration, and these malformations are well visualized by current neuroimaging techniques. This report describes a patient with unilateral schizencephaly and poorly controlled complex partial seizures who was found to have a temporal lobe seizure focus; anterior temporal lobectomy produced nearly complete control of the seizures. Despite the extensive malformation, relatively restricted resection was of significant benefit. The principles of seizure focus localization and resection are applicable to the management of patients with schizencephaly. PMID- 1595055 TI - Cancer of the head of pancreas or chronic pancreatitis? A diagnostic dilemma. PMID- 1595056 TI - Reoperative thyroid surgery. AB - BACKGROUND: Patients with thyroid cancer are sometimes denied repeat thyroid operations for fear of an increased risk of complications. METHODS: We therefore reviewed our experience in 114 patients with benign or malignant thyroid tumors who underwent 116 thyroid reoperations with or without other procedures. All patients had undergone at least one prior thyroid operation and 16 patients had undergone from two to four thyroid operations before referral. The initial histologic diagnosis before reoperation was thyroid carcinoma in 79 patients, papillary carcinoma in 47 patients, follicular carcinoma in 17 patients, medullary carcinoma in 9 patients, and Hurthle cell carcinoma in 6 patients. Benign disease was present in 35 patients. In 62 patients with cancer, reoperations were performed because of suspected persistent or recurrent disease; one of these patients underwent two reoperations by us. In 17 patients reoperation was to complete total thyroidectomy, primarily so that radioactive iodine could be used to scan for and treat metastatic disease. RESULTS: Among the 116 reoperations, 102 were completion total thyroidectomy, 8 were near-total or subtotal thyroidectomy, and 6 were completion lobectomy. Histologic examination at reoperation revealed thyroid carcinoma in 51 cases (64%) among the 79 patients who had undergone 80 operations for previous thyroid cancer. Recurrent or persistent cancer was present in 49 of 63 (78%) reoperations for patients with papillary, medullary, and Hurthle cell cancer but in only 2 of 17 (12%) patients with follicular cancer. Cancer also occurred in 8 cases (22%) of the 36 reoperations in 35 patients who initially had benign lesions. Complications included one permanent and one transient palsy of the recurrent laryngeal nerve; both occurred on the side of a previous partial or subtotal lobectomy. Other complications included temporary hypoparathyroidism in four patients, seromas in two patients, and a keloid in one patient. CONCLUSIONS: This study documents that reoperations can be performed with minimal morbidity. Thus patients should not be denied the chance to undergo removal of a persistent tumor or the remnant normal thyroid tissue because of the fear of complications. PMID- 1595057 TI - Partial portacaval shunt: renaissance of an old concept. AB - BACKGROUND: Partial diversion of the portal system aims to reduce portal pressure sufficiently to prevent variceal hemorrhage but still maintain adequate hepatic portal flow. METHODS: Partial portacaval shunts were performed in 25 patients with cirrhosis with portal hypertension and esophageal varices, either as a primary procedure (n = 16) or for failure of endoscopic sclerotherapy (n = 9), with ringed polytetrafluoroethylene prostheses (8, 10, or 12 mm). RESULTS: All patients have now been followed up for at least 1 year. The operative mortality rate (2 months) was 4%. In 24 patients who survived beyond the initial perioperative period, there was no recurrence of variceal bleeding. Cumulative shunt patency (up to 4 years) is 96%. Acute encephalopathy was detected in two patients (8%), but no patients had signs of chronic encephalopathy. Intraoperative pressure measurements revealed a significant correlation between decreasing diameter of the graft and the percentage reduction of the portacaval pressure gradient. Selective angiography, performed 1 year after surgery, revealed that hepatopetal flow was maintained in 70% of patients with a 10 mm shunt. CONCLUSIONS: It is possible to achieve a partial portacaval shunt, related to the diameter of the prosthesis, that preserves hepatopetal flow in the majority of patients and is associated with a very low incidence of shunt thrombosis. This effectively prevents recurrent variceal bleeding and significant postoperative encephalopathy. The performance of subsequent orthotopic liver transplantation is not compromised. The technique is recommended, either as a primary procedure or when sclerotherapy has failed, in patients with good liver function who are unlikely to require early liver transplantation (grade A and some grade B cirrhosis). PMID- 1595058 TI - Postoperative ascitic leaks: the ongoing challenge. AB - BACKGROUND: The leak of ascitic fluid from surgical incisions is thought to be associated with a very high mortality rate. There have been few reports, however, focusing on the clinical characteristics, management, or mortality rates of this condition. METHODS: During a 10-year period, 18 patients with postoperative ascitic fluid leaks were treated. All patients had ascites before surgery and all had liver disease; in 13 of the 18 patients alcoholic liver disease was the cause of ascites. RESULTS: Ten of the 18 patients died (56%). Midline incisions were more often associated with recalcitrant leaks and fatal complications than were transverse incisions. CONCLUSIONS: Early consideration of fascial dehiscence and prompt repair is emphasized. The most effective predictor of survival was cessation of the leak. PMID- 1595059 TI - Intraoperative radionuclear 125I-labeled metaiodobenzylguanidine scanning of pheochromocytomas and metastases. AB - We developed a technique to assess the feasibility of intraoperative radionuclear detection of pheochromocytomas and their metastases. Thirteen patients were entered into the study: five control subjects with nonchromaffin adrenal tumors, eight with pheochromocytomas, and one of these patients showing bone metastasis. Each subject received thyroid blockade and an intravenous injection of 500 microCi (37 megabecquerels) 125I-labeled metaiodobenzylguanidine (MIBG) 3 days before surgery. In the five control subjects, adrenal tumor uptake never exceeded the liver or spleen uptake. One patient with a negative preoperative MIBG scan demonstrated no intraoperative uptake. Five patients with pheochromocytoma had positive preoperative scans and in one other patient preoperative scanning was not done. In each of these six patients intraoperative count ratio of pheochromocytoma/liver from 14:2 to 250:16 and pheochromocytoma/contralateral adrenal ratio from 60:1.5 to 60:16 was demonstrated. An intraoperative scan in one of these patients detected two small metastatic tumor deposits previously overlooked by the surgeon after removing a larger mass that had been localized by a preoperative 131I-MIBG scan. A negative preoperative scan in one patient was followed by an intraoperative scan demonstrating a bone metastasis with a ratio of metastasis/normal bone of 10:0.5. Specimen studies demonstrated a significant MIBG uptake ratio of tumor/plasma ranging from 95 to 667 (average 404 +/- 242) greater than in control subjects (average 25 +/- 41); in the patient with metastasis the uptake ratio of metastasis/normal bone reached 98.4. We conclude that intraoperative 125I-MIBG scanning might detect pheochromocytoma deposits overlooked by preoperative 131I-MIBG scans. PMID- 1595060 TI - Effects of laparotomy on systemic macrophage function. AB - Surgical trauma induces immunosuppression that may adversely influence survival. This study examined the effect of laparotomy on two different macrophage populations, peritoneal macrophages (PM phi) and Kupffer cells. Female, 6- to 8 week old, CFW/C3H-HeN mice (n = 160) were randomly allocated to one of three study groups: control, ether anesthetic only, or ether anesthetic and laparotomy. On postoperative days 1 and 3, PM phis and Kupffer cells were harvested and assayed for superoxide anion production (O2-), percent macrophage phagocytosis of Candida albicans (CAP), percent C. albicans killed by macrophages (CAK), percent major histocompatibility complex (MHC)-class II antigen expression, and antigen presentation. Macrophages isolated on postoperative day 1 were also cocultured with 100 units/10(6) cells/ml interferon-gamma (IFN-gamma). Laparotomy significantly impaired microbicidal activity (O2-, percent CAP, and percent CAK) and antigen presentation on postoperative day 1. On postoperative day 3, O2- and antigen presentation were increased significantly (p less than 0.05) over control values, indicating a rebound phenomenon. Kupffer cell microbicidal function was unchanged on postoperative days 1 and 3. The initial immune impairment (PM phis: O2-, CAP, and CAK) was abrogated by IFN-gamma treatment. In immunosuppressed hosts after injury, administration of macrophage-activating factors such as IFN gamma could be of therapeutic benefit. PMID- 1595061 TI - Early detection of breast carcinoma: a comparison of palpable and nonpalpable lesions. AB - A retrospective study of 536 needle-localization biopsies of nonpalpable breast lesions and 623 excisional biopsies of palpable breast lesions was performed. Carcinoma was present in 17.9% of needle-localization biopsy specimens and in 11.1% of excisional biopsy specimens. Noninvasive carcinoma constituted 50% of carcinomas detected by needle-localization biopsy and only 7.3% of carcinomas detected by excisional biopsy (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was associated with axillary lymph node metastasis in 9.8% of patients who had axillary dissection, compared with 37.7% of patients with invasive carcinoma detected by excisional biopsy of a palpable mass (p less than 0.005). Invasive carcinoma detected by needle-localization biopsy was less than 2 cm in size (T1) in 93.5% of biopsy specimens; in contrast, invasive carcinoma detected by excisional biopsy was less than 2 cm in size in only 54.7% of biopsy specimens (p less than 0.005). Nonpalpable breast lesions that proved to be invasive carcinoma were pathologic stage I in 82.9% of patients. Palpable breast lesions that proved to be invasive carcinoma were pathologic stage I in only 47.2% of patients. Survival benefits of mammographic screening and biopsy of nonpalpable lesions are likely the result of detection of invasive carcinoma at an early stage and detection of noninvasive carcinoma that may later develop into or mark increased risk of invasive carcinoma. PMID- 1595062 TI - Myocardial depression characterizes the fatal course of septic shock. AB - The relationship between cardiac and vascular abnormalities was studied in 68 patients with established septic shock. At time of hemodynamic evaluation, after initial resuscitation, there was no significant difference in arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac index between the 38 survivors of shock and the 30 patients who died of shock, but the left ventricular stroke work index and the right ventricular (RV) stroke work index were higher in survivors than in those who died (mean +/- SD: 25.0 +/- 9.1 vs 20.1 +/- 9.4 gm/m2 [p less than 0.05] and 6.6 +/- 3.6 vs 4.8 +/- 2.8 gm/m2 [p less than 0.05], respectively). Survivors had also higher thermodilution RV ejection fraction and lower RV end-diastolic volumes than had those who died (43.9% +/- 16.3% vs 31.1% +/- 13.7% [p less than 0.01] and 82 +/- 30 vs 99 +/- 31 ml/m2 [p less than 0.05], respectively). Calculated systemic vascular resistance was similar in the two groups, but vasopressors had been required in 22 (58%) of 38 survivors and 25 (83%) of 30 patients who died (p less than 0.01). Moreover, when the patients were separated into two groups according to their cardiac output, higher or lower than 3 L/min/m2, in both subgroups patients who died had lower blood pressure than had survivors. Blood lactate levels were significantly lower in survivors than in nonsurvivors (5.1 +/- 2.1 vs 8.1 +/- 4.7 mEq/L, p less than 0.01). Final data obtained before recovery of shock or death indicated that the survivors had higher arterial pressure, lower pulmonary artery pressure and right atrial pressure, higher stroke volume, and higher RV ejection fraction than had the patients who died. No survivors but all patients who died had been treated with vasopressors. These data therefore indicate that death as a result of septic shock is characterized by both myocardial depression and altered vascular tone and both are probably interrelated. PMID- 1595063 TI - Permanent acceptance of liver allografts by intraportal injection of donor spleen cells in rats. AB - Antigen pretreatment through the oral or intraportal route has been reported to suppress antibody formation or delayed-type hypersensitivity (DTH) response to the same antigens. However, this effect on allografted organs has not been well studied. In this study we evaluated the efficacy for suppression of antibody formation and DTH response to the allogeneic antigens and tried to prolong liver allograft survival in rats. Male ACI (RT1a) rats were used as donors and male BUF (RT1b) rats as recipients. Intraportal or intravenous injection of spleen cells (SPCs) (5 x 10(7)) was performed through the mesenteric vein or the tail vein, respectively. The anti-ACI DTH response was tested by ear challenge of ACI SPCs. Cytotoxic antibody was assessed by complement-dependent cytotoxicity assay. ACI rat liver was transplanted orthotopically to BUF rat by the cuff technique 10 days after SPC injection. Cytotoxic antibody titer rose to X2(6) to X2(8) at 7 to 10 days after intravenous injection of SPCs. However, intraportal injection of the cells rarely caused a rise in antibody titer and even strongly suppressed subsequent antibody formation induced by intravenous injection when given 10 days before. The DTH response was also suppressed by intraportal injection of SPCs, with a mean value of 0.18 +/- 0.13 mm versus 0.67 +/- 0.19 mm for controls or 0.46 +/- 0.04 mm with intravenous injection. Liver-allografted rats died between 9 and 11 days, averaging 10.1 +/- 0.7 days in the control group. All seven transplants injected intraportally with donor SPCs survived more than 100 days, whereas six of eight rats injected intravenously with donor SPCs died of bleeding from the surface of the liver grafts within 12 hours after grafting, with signs similar to those of hyperacute rejection. Four of five rats injected intraportally with F344 (third-party) SPCs died of acute rejection in the same way the control rats died. The liver allograft-bearing rats had permanently accepted ACI skin grafts when tested 60 days after liver transplantation but rejected F344 skin grafts in the normal fashion. Intraportal injection of donor SPCs markedly suppressed the antibody formation, as well as the DTH response, and completely blocked liver allograft rejection. Moreover, the liver allograft bearing rats proved to be fully tolerant of the donor antigen. This method might be a promising modality for inducing donor-specific tolerance in liver transplantation. PMID- 1595064 TI - Healing of high-porosity polytetrafluoroethylene arterial grafts is influenced by the nature of the surrounding tissue. AB - The aim of this study was to determine the influence of the nature of the perigraft tissue in the healing pattern of high-porosity polytetrafluoroethylene (PTFE) vascular grafts. Nine-centimeter long segments of unreinforced experimental high-porosity (60 microns) PTFE grafts were placed as abdominal aortic interposition in mongrel dogs. Three grafts served as controls (group A); in five dogs (group B) a 25 x 25 cm piece of devascularized omentum was wrapped around the graft. In five dogs (group C) the omentum with its own vascular supply was completely wrapped around the graft. Animals were killed 4 weeks after surgery. The percentage of thrombus-free area was 31% in group A grafts, 39% in group B grafts, and 79% in group C grafts (p less than 0.01). Scanning electron microscopy showed many confluent areas of endothelium-like cells in the midportion of group C grafts, corresponding to capillary ingrowth. Transmural endothelial migration was more evident in group C grafts. We conclude that the nature of the perigraft tissue influences transmural capillary migration and the endothelialization rate of high-porosity PTFE grafts in dogs. Agents able to increase capillary formation in the perigraft tissue might improve endothelialization of vascular grafts. PMID- 1595065 TI - Load-insensitive assessment of myocardial performance after tumor necrosis factor alpha in dogs. AB - Tumor necrosis factor-alpha (TNF alpha) has been implicated as an endogenous mediator of the cardiovascular manifestations of sepsis and septic shock. We studied the acute effects of a single dose (50 or 200 micrograms/kg) of intravenous recombinant human TNF alpha (rhTNF alpha) on myocardial function in halothane-anesthetized dogs. Regional cardiac dimensions were measured by using sonomicrometry. Intracavitary left ventricular, ascending aortic, and pulmonary artery pressures were measured by use of micromanometers. Cardiac index was determined by means of thermodilution. Myocardial performance was analyzed by assessing changes in the slope of the left ventricular end-diastolic length stroke work relationship obtained by performing transient vena caval occlusions. Animals were resuscitated by means of normal saline solutions to maintain baseline regional end-diastolic length. Over a 3-hour period of observation, rhTNF alpha decreased systemic vascular resistance index, but the cytokine did not compromise intrinsic myocardial performance. The circulatory response to rhTNF alpha was a hyperdynamic state characterized by tachycardia, augmented cardiac index, and increased intrinsic myocardial contractility (leftward shift of the left ventricular end-diastolic length-stroke work relationship). In addition, rhTNF alpha caused systemic acidosis and increased plasma levels of prostacyclin metabolite (6-keto-prostaglandin F1 alpha). After the dose of rhTNF alpha large volumes of fluid were required to maintain baseline end-diastolic length. We conclude that in the acute setting, rhTNF alpha elicits abnormalities in peripheral vascular tone that are not accompanied by depression of myocardial function. PMID- 1595066 TI - Leiomyosarcoma of the small intestine associated with von Recklinghausen's disease: report of a case. AB - A 54-year-old woman with intestinal multiple smooth muscle tumors including leiomyosarcoma, epithelioid leiomyoma, and leiomyomas in association with von Recklinghausen's disease is reported. Thirteen years after the excision of an intestinal leiomyosarcoma, another leiomyosarcoma arose in a different area of the jejunum and was also completely resected. Although leiomyomas are occasionally recognized in patients with von Recklinghausen's disease and a gastrointestinal neoplasm, there have been no other reports of leiomyosarcomas. Careful observation of the tumor is necessary and, if a rapid increase in tumor size is recognized, malignant tumor may have arisen and early surgical treatment is required. PMID- 1595067 TI - Infiltrating syringomatous adenoma of the nipple. AB - Infiltrating syringomatous adenoma of the nipple is a distinct, benign clinical entity. It is similar histologically to a syringoma, a benign tumor originating in the ducts of the dermal sweat glands. When located in the nipple, this lesion has been mistaken for nipple duct adenoma or tubular carcinoma. Infiltrating syringomatous adenoma of the nipple is locally infiltrating but does not metastasize. Appropriate local management depends on an accurate diagnosis. Following is a case report, review of the literature, and therapeutic options for infiltrating syringomatous adenoma of the nipple. PMID- 1595068 TI - Late anastomotic recurrence after radical resection of carcinoma of the ampulla of Vater: case report. AB - Although 5-year survival after radical resection for ampullary carcinoma has traditionally been regarded as a cure, recent reports have documented late recurrences from these tumors. This case report describes an anastomotic recurrence developing more than 5 years after a curative resection for ampullary carcinoma. This case report is unique in its location, unusually late development, and proposed mechanism of occurrence. PMID- 1595069 TI - Mohs' micrographic surgery in the management of soft tissue sarcomas of the extremities. PMID- 1595070 TI - Texas BNE's rules. On delegation of selected nursing tasks by registered nurses to unlicensed personnel. PMID- 1595071 TI - Increase teenage AIDS ed, sex education says ANA. PMID- 1595073 TI - Nurses tip sheet on. Advance medical directives. PMID- 1595072 TI - As eagles fly. PMID- 1595074 TI - Purification of the main beta-toxin from Tityus serrulatus scorpion venom using high-performance liquid chromatography. AB - The venom of the Brazilian scorpion Tityus serrulatus was fractionated using high performance liquid chromatography which allowed us to purify in two steps the main beta-type toxin of the venom. The toxin constituted about 15% of the absorbance at 280 nm and 50% of the toxicity of the venom. According to its amino acid content, its electrophoretic migration on Phast-Gel homogenous 20 and its biological properties both in vivo by intracerebroventricular injection to the mouse (LD50 = 30 ng/kg mouse) and in vitro by competition receptor assay on rat brain synaptosomes (K0.5 = 80 pM), the toxin was identified as toxin Ts VII already purified from the same venom using low-pressure liquid chromatography (BECHIS et al., 1984 Biochem. biophys. Res. Commun. 122, 1146). The high performance liquid chromatographic technique used improved by a factor of four the amount of toxin purified. PMID- 1595075 TI - Issues in management of scorpion sting in children. AB - All children admitted to Madina Maternity and Children's Hospital, Saudi Arabia, in 1989 because of scorpion stings (primarily Leiurus quinquestriatus) were studied. Of 96 children studied, 20 suffered either shock, pulmonary oedema or both. These 20 shared characteristic clinical features such as vomiting, priapism and failure to maintain normal temperature and/or blood pressure. The management protocol emphasized fluid restriction and the i.v. administration of venom antitoxin. Doubling the recommended dose did not improve the outcome. Two children died and the rest recovered. PMID- 1595076 TI - Risk indicators after envenomation in humans by Echis coloratus (mid-east saw scaled viper). AB - To determine the frequency, severity and predictors of bleeding and azotemia after envenomation in humans by Echis coloratus, a retrospective survey of 68 cases in Israel between 1970 and 1989 was carried out. We used univariate and multivariate analyses of clinical variables on admission for the outcome variables of bleeding, hemoglobin and platelet levels, and blood urea. Within hours or days after envenomation, a major bleeding episode occurred in 18% of the victims, a drop in hemoglobin to 10 g/dliter or less in 14%, and an increase in blood urea to 9 mmole/liter or more in 15%. These complications correlated with time interval between envenomation and hospital admission, and the following admission variables: degree of bleeding, hemoglobin level, platelet and white blood cell counts, blood urea and proteinuria. Complications were unlikely in patients who were presented with all of the following: a hemoglobin level of 13 g/dliter or more, a platelet count of 100,000/mm3 or more, a blood urea level of 7 mmole/liter or less, no proteinuria and no bleeding. Treatment on admission with a specific monovalent antiserum was associated with a shorter duration of hemostatic failure and a reduced incidence of anemia and thrombopenia. Infusion of fresh frozen plasma on admission did not appear to be effective in preventing complications. PMID- 1595077 TI - A new bradykinin-potentiating peptide (peptide P) isolated from the venom of Bothrops jararacussu (jararacucu tapete, urutu dourado). AB - Several bradykinin potentiators were identified in the venom of Bothrops jararacussu by chromatographic techniques and biological assays. One of them which was isolated inhibited the angiotensin-converting enzyme in vitro and potentiated the bradykinin-induced lowering of the arterial pressure in the rat. PMID- 1595078 TI - Occurrence of a new toxin and tetrodotoxin in two species of the gastropod mollusk Nassariidae. AB - The lethalities of 102 specimens of three species of the gastropod mollusk Nassariidae, collected from fish markets in Taiwan, were examined. The frequency of toxicity in Zeuxis scalaris and Z. castus-like specimens was 94 and 41%, respectively. The range of lethal potency in toxic specimens of Zeuxis scalaris and Z. castus-like was 2-140 and 2-13 mouse units, respectively, while all tissues of Z. castus were non-toxic. The toxins were partially purified from the toxic specimens of Z. scalaris and Z. castus-like. Two toxin fractions were obtained from the extract of each species of Nassariidae by using Bio-Gel P-2 column chromatography. Analyses by thin layer chromatography, electrophoresis, high performance liquid chromatography and ultraviolet spectroscopy, showed that toxin fraction I contained tetrodotoxin while toxin fraction II contained a new neurotoxin. PMID- 1595079 TI - Use of HPLC to demonstrate variation of venom toxin composition in the Thailand cobra venoms Naja naja kaouthia and Naja naja siamensis. AB - The composition of the venoms of Naja naja kaouthia and Naja naja siamensis from different commercial sources has been investigated using both ion-exchange and reverse-phase high-pressure liquid chromatography (RP-HPLC) in order to investigate variation in toxin contents. The venoms contained identical major toxin components, although in different relative concentrations. The venom collected separately from the left and right glands of individual snakes were virtually the same as judged by RP-HPLC. The cytotoxin CT-II, which was previously only reported to be present in Naja naja siamensis venom, was detected in all the venoms investigated. Two long neurotoxin homologues have also been isolated. PMID- 1595080 TI - Increase of permeability of synaptosomes and liposomes by the heavy chain of tetanus toxin. AB - In search of a role for the heavy chain of tetanus toxin in poisoning, its actions on natural and artificial membranes have been assessed. The heavy chain increases the permeability of synaptosomes to lactate dehydrogenase and potassium ions, and promotes the outward shift of the lipophilic cation tetraphenylphosphonium which is a particularly sensitive indicator for depolarization. Independent of the assay system the potency of the heavy chain is high, i.e. in the range of about 1 nM, whereas its efficacy is low. Its potency is decreased by the addition of the light chain and by treatment of the synaptosomes with the C-terminal fragment C of the heavy chain, but not with its N-terminal fragment beta 2. Single- or two-chain toxin itself is inactive, and so are the light chain or the two heavy chain fragments beta 2 and C. Liposomes were made from phosphatidylcholine and phosphatidylserine or gangliosides and loaded with calcein. At pH 6 the outflow of calcein is promoted in the order heavy chain greater than toxin much greater than fragment beta 2, and the action of toxin is promoted by ganglioside. At pH 5, fragment beta 2 is nearly as active as the heavy chain and more potent than the toxin. The heavy chain, but neither of the fragments, is strongly adsorbed in hydrophobic interaction chromatography and caused aggregation of polystyrene-divinylbenzene beads. Evidence for polymerization of heavy chains is lacking in zonal centrifugation. It is concluded that both domains of the heavy chain co-operate to exert the membranal events described, and that the heavy chain is partially hidden by the light chain in the complete toxin molecule. PMID- 1595081 TI - Isolation and characterization of dracotoxin from the venom of the greater weever fish Trachinus draco. AB - Dracotoxin, a protein possessing toxic, membrane depolarizing and hemolytic activities, was isolated from the crude venom of the greater weever fish Trachinus draco. The purification involved ammonium sulfate precipitation of crude venom followed by gel filtration on a high performance liquid chromatograph column. About 300 micrograms of dracotoxin was obtained from 18 mg of crude venom proteins extracted from one average size fish. Dracotoxin consists of a single polypeptide of about 105,000 mol. wt. It hemolyzed rabbit erythrocytes with an EC50 of 3 ng/ml. Rabbit erythrocytes possessed binding sites for dracotoxin on their surface. Preincubation of dracotoxin with rabbit ghosts increased its EC50 value for rabbit erthrocytes from 3 to 25 ng/ml. Incubation of dracotoxin with enriched glycophorin fraction from rabbit erythrocytes also led to an increase in the EC50 to 70 ng/ml. The high specificity of dracotoxin for rabbit erythrocytes resembles that of staphylococcal alpha-toxin. Dracotoxin, however, caused hemolysis even at 4 degrees C and did not interact with cholesterol indicating substantial differences between the two hemolysins. Dracotoxin represents a major toxic component of T. draco venom. PMID- 1595082 TI - Biological activities of venoms from South American snakes. AB - Standard assay procedures for the characterization of snake venoms, developed by the World Health Organization (WHO) Collaborating Centre for the Control of Antivenoms (CCCA), were used to analyse 33 snake venoms including eight International Reference Venoms for the assessment of lethal, defibrinogenating, procoagulant, haemorrhagic and necrotizing properties. The International Reference Venoms were assayed as part of an International Collaborative Programme for the evaluation of Venoms and Antivenoms; the results showed a close relationship to those obtained by the CCCA. Twenty-five venoms from 13 different species of medically important snakes from South America were assayed as standardized by the WHO-CCCA. Additionally, evaluation of lethal activity by the i.p. and intra cerebroventricular routes, proteolytic effects and venom-induced edema were also determined. Venom yields from captive snakes are also presented. Among the venoms examined, from the subfamily Crotalinae, the members of the genera Bothrops and Lachesis had strong haemorrhagic, proteolytic and edema inducing activities, whereas all Crotalus durissus species had none. The Elapinae, Micrurus frontalis showed no procoagulant, defibrinogenating, haemorrhagic, necrotizing or proteolytic activities. The results reflect differences among individual samples of the same species and of different geographical regions. The results suggest that there is little or no relationship between the properties of the different venoms and that the determination of one effect cannot predict the value of the others. Therefore, the characterization of the different activities of snake venoms is necessary if toxicity is to be properly evaluated and neutralized. PMID- 1595083 TI - Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme. AB - The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate. PMID- 1595084 TI - Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on blood and spleen natural killer (NK) cell activity in the mouse. AB - The immunotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were studied in male A/J mice after a loading dose of 5 micrograms TCDD/kg body wt. followed by 3 weekly maintenance doses of 1.42 micrograms TCDD/kg b.w. administered intraperitoneally. Tissue samples and immune cells were prepared on two occasions, i.e. on days 28 and 120 after the first injection of TCDD. This dose of TCDD evoked classical histological signs of liver damage and lipid accumulation, as well as thymic atrophy. Red (RBC) blood cell counts were significantly lowered in the TCDD group on day 28, but were normal on day 120. White (WBC) blood cell counts were normal in the TCDD group. Natural killer (NK) cell activity increased 3.4-fold (P less than 0.01) and 2.2-fold (P less than 0.01) in the blood and spleen, respectively, after 28 days, and these effects persisted on day 120. The increased NK-cell activity occurred concomitantly with a decreased proliferative response of spleen lymphocytes to the T-cell mitogen concanavalin A after both 28 (65%) and 120 days (58%). The proliferative response of spleen cells to the B-cell mitogen lipopolysaccharide seemed, however, unaffected. We have thus shown for the first time that TCDD induces an increased activity of NK cells that occurs simultaneously in the blood and spleen. This effect may indicate a general compensatory activation of the body's defences brought about by disturbances in the function of other arms of the immune system. PMID- 1595085 TI - alpha-Hydroperoxy diethyl peroxide, an unusual natural compound isolated from an ascidian (Phallusia mammillata): acute toxicity in DDY mice. AB - alpha-Hydroperoxy diethyl peroxide, a novel compound found in the tunic of ascidians, has two peroxide moieties per molecule. Since ascidians are a widely served food item in Japan, human exposure to this compound potentially exists in the seafood preparation industries. No toxicological data have so far been published on this compound, and so we determined the intraperitoneal 6-day LD50 in mice and conducted histopathological examinations. The 6-day LD50 was found to be 199 mg/kg with 95% confidence limits of 126-314 mg/kg. Histopathological examination revealed necrosis induced in a variety of cells that had been directly exposed to the compound. These cells included hepatocytes, parenchymal pancreatic cells and fat cells. It is concluded that direct contact with this compound is likely to elicit cellular necrosis of various organs. The specific toxicological effects are probably dependent on the route of exposure. PMID- 1595086 TI - Genetic toxicology studies of an anti-AIDS drug. AB - SC-48334 (N-butyldeoxynojirimycin) is an experimental anti-AIDS drug which is currently in clinical trials. This drug is an aminosugar derivative. Its biological properties have been previously published [1]. Since many antiviral agents which are nucleic acid analogs exhibit mutagenic and/or clastogenic properties, the genotoxic potential of SC-48334 was examined in the Ames Salmonella/microsome assay, the Chinese hamster ovary cell/hypoxanthine guanine phosphoribosyl transferase (CHO/HGPRT) assay and the mouse bone marrow micronucleus assay. No toxic or mutagenic effects were observed in either the bacterial or mammalian in vitro mutation assays. Likewise, no clastogenic activity was observed in the in vivo micronucleus assay. Therefore, the administration of this drug in humans is not likely to have mutagenic effects and would probably not have a carcinogenic effect. PMID- 1595087 TI - Inhibition of human term placental and fetal liver glutathione-S-transferases by fatty acids and fatty acid esters. AB - Glutathione-S-transferase (GST) activity from human term placenta and human fetal liver towards 1-chloro-2,4-dinitrobenzene as the second substrate was significantly inhibited by the saturated fatty acids, stearic (SA) and palmitic (PA) acids and fatty acid esters, ascorbyl stearate (Asc-S) and ascorbyl palmitate (Asc-P). The nature of inhibition of human placental GST was competitive towards CDNB with Ki values of 3.1, 10.0, 13.5 and 18.5 microM for Asc-S, Asc-P, PA and SA, respectively. The inhibitory effect of Asc-S on human term placental GST was reversible. I50 values for Asc-S, Asc-P, SA and PA were 15, 45, 83 and 78 microM, respectively, for partially purified human fetal liver GSTs and 21, 6, 88 and 117 microM, respectively, for partially pure rat liver GSTs. The evidence suggests that Asc-S, Asc-P, SA and PA are potent inhibitors especially of the pi-class of GST. PMID- 1595088 TI - Alterations in hepatic phase I and phase II biotransformation enzymes by garlic oil in rats. AB - Studies were conducted to examine the effect of a single and repeated administrations of garlic oil (diallyl sulfide) on Phase I and Phase II biotransformation enzymes in rats. Adult, male Sprague-Dawley rats treated with a single dose of garlic oil (500 mg/kg i.p.) showed a significant depression of hepatic cytochrome P-450, aminopyrine N-demethylase and aniline hydroxylase while microsomal protein content, cytochrome b5, NADPH-cytochrome c reductase, benzphetamine N-demethylase and cytosolic glutathione, S-transferase remained unaffected 24 h following the treatment. Although certain microsomal enzymes were depressed, there was no liver damage caused by garlic oil as judged by the putative serum enzyme test. On the other hand, daily administration of garlic oil (50 mg/kg i.p. for 5 days) produced a significant increase in hepatic cytochrome P-450, aminopyrine N-demethylase and benzphetamine N-demethylase activities, but not in the rest of the aforementioned parameters of biotransformation reactions. These data indicate that the effect of garlic oil on the hepatic drug metabolizing enzyme system is dose-dependent. PMID- 1595089 TI - Production of a toxic, novel mammalian metabolite of N-methylcarbazole predicted by a fungal cell model of mammalian metabolism. AB - The formation of N-hydroxymethylcarbazole (NHMC), carbazole, 1-hydroxy-N methylcarbazole, 2-hydroxy-N-methylcarbazole, and 3-hydroxy-N-methylcarbazole as products of mammalian liver microsomal metabolism of N-methylcarbazole (NMC) has been documented by several investigators. In previous studies in our laboratory, the fungus Cunninghamella echinulata (ATCC 9244) produced two new metabolites, 3 hydroxy-N-hydroxymethylcarbazole (3-OH-NHMC), and 3-hydroxycarbazole (3-OH carbazole), in addition to the known mammalian metabolites, NHMC and carbazole. One of the two novel metabolites isolated from the microbial models, 3-OH-NHMC, was also identified and characterized in rat liver microsomes by analytical (HPLC) and spectral (UV and NMR) comparisons with a reference standard. The two metabolites, 3-OH-NHMC and 3-OH-carbazole, were shown to be cytotoxic to cultured rat hepatocytes as assessed by lactate dehydrogenase (LDH) leakage and neutral red (NR) uptake. These studies demonstrate the prospective potential of microbial models for predicting the formation of metabolites from drugs and other xenobiotics in mammalian systems. PMID- 1595090 TI - Effects of amaranth on F1 generation mice. AB - The color additive, amaranth, was given in the diet to provide dietary levels of 0 (control), 0.03, 0.09 and 0.27%, from 5 weeks of age in F0 generation mice to 9 weeks of age in F1 generation mice, and some reproductive, developmental and behavioral parameters were measured. There was no effect on the parameters of litters, litter size, pup weight and litter weight. The body weight of pups during the lactation period in the treatment groups increased less significantly, and the survival index at postnatal day (PND) 21 of the amaranth 0.27% group was reduced. Developmental parameters, direction of swimming on PND 4 in male pups and olfactory orientation in each sex were significantly reduced in the treatment groups. The dose levels of amaranth in this study influenced some reproductive, developmental and behavioral parameters in mice. PMID- 1595091 TI - Biphasic effects of smoking on human serum dopamine-beta-hydroxylase activity. AB - To investigate the chronic effects of smoking on sympathetic nerve activity, serum dopamine-beta-hydroxylase (DBH) activity was determined in 119 male non smokers and 183 age-matched male smokers. The smokers were classified into 3 groups: 51 light smokers (1-19 cigarettes/day), 76 moderate smokers (20 cigarettes/day), and 56 heavy smokers (more than 20 cigarettes/day). The light smokers had the highest mean DBH activity, and the heavy smokers had the lowest mean DBH activity in the 4 groups. These results suggest that light smoking stimulates the sympathetic nervous system, but that heavy smoking depresses the system. These biphasic changes in DBH activity are similar to the pharmacological effects of nicotine on the peripheral sympathetic nervous system. PMID- 1595092 TI - A scanning electron-microscopic study of the effects of methylmercury on the neuronal cytoskeleton. AB - Cultured mouse neuroblastoma cells, Neuro-2a (c1300), were exposed to 2.5 and 5.0 microM methylmercury (MeHg) with or without the concomitant administration of 10 mM glutathione for 24 h. Treated cells viewed by scanning electron microscopy (SEM) appeared sponge-like and were surrounded by fragments of cytoplasmic processes. SEM cytoskeletal preparations of treated cells showed a collapsed matrix containing globular bodies. Microtubules were not seen in treated cells, but intermediate and microfilaments were observed. SDS-PAGE analysis of cytoskeletal extracts revealed bands ranging in size from 90 to 27 kDa in all treatment groups except in the 5.0 microM-MeHg-treated group. This group showed a single band co-migrating with actin. Cells exposed to glutathione alone or concomitantly with MeHg appeared similar to control cells under all experimental conditions. These observations suggest that MeHg may predominantly affect microtubules to form a condensation product. PMID- 1595093 TI - Species differences in the nephrotoxic response to S-(1,2 dichlorovinyl)glutathione. AB - The present study was carried out to investigate the species differences in the nephrotoxic response to S-(1,2-dichlorovinyl)glutathione (DCVG) using rats, hamsters and guinea-pigs. DCVG was given intraperitoneally in physiological saline to groups of 5 animals at doses 0, 165 and 330 mumol/kg. Urine was collected for 24 h and the animals were then sacrificed. Significantly increased levels of urinary glucose, N-acetyl-beta-D-glucosaminidase, gamma-glutamyl transpeptidase, proteins and blood urea nitrogen were observed in rats at both dose levels of DCVG. An increase, but not of similar magnitude, of these biochemical parameters was noted in hamsters only at the higher dose of DCVG. Guinea-pigs showed significant increases in these biochemical parameters at the lower dose, but not at the higher dose. Light-microscopic studies showed increasing proximal tubular necrosis (PTN) in rats with increasing dose of DCVG, but PTN involving straight tubules only was observed at the higher dose in hamsters. PTN was again observed in guinea-pigs at the lower dose, but not at the higher dose of DCVG. PMID- 1595094 TI - Animal stroke models. PMID- 1595095 TI - Prevalence and etiology of dementia in a Japanese community. AB - BACKGROUND AND PURPOSE: We sought to determine the type-specific prevalence of dementia and its risk factors in elderly persons from the Japanese community of Hisayama. METHODS: We studied the prevalence of dementia in 887 Hisayama residents (353 men and 534 women) aged 65 years or older (screening rate, 94.6%) using various items of clinical information, neurological examination, and dementia scales. We also studied brain morphology in 50 of 59 determined to have dementia by computed tomography or autopsy during the subsequent 54-month period. Factors relevant to dementia were compared between 27 patients with vascular dementia and 789 control subjects without dementia in a retrospective fashion. RESULTS: The prevalence rate of dementia among Hisayama residents aged 65 or older was estimated at 6.7%, with a females to males ratio of 1:2. Among 50 cases of dementia in which brain morphology was examined, the frequency of vascular dementia was 56%; this rate was 2.2 times higher than that for senile dementia of the Alzheimer type. Aging, hypertension, electrocardiographic abnormalities, and high hematocrit were significantly (p less than 0.05) and independently associated with the occurrence of vascular dementia. CONCLUSIONS: Prevalence of dementia among the Hisayama residents was relatively identical to that previously reported, but vascular dementia was more predominant. Risk factors for vascular dementia were similar to those for lacunar infarcts. Control of hypertension may be a key to reducing dementia among the Japanese population. PMID- 1595096 TI - Cranial computed tomographic observations in multi-infarct dementia. A controlled study. AB - BACKGROUND AND PURPOSE: We compared cranial computed tomography findings among 58 multi-infarct dementia index cases and 74 multi-infarct control subjects without cognitive impairment to identify potential determinants of multi-infarct dementia. METHODS: The cranial computed tomography records of acute ischemic stroke patients with a history of multiple cerebral infarcts were compared to determine the number, location, and size of cerebral infarcts; the pattern of infarction; brain volume loss; and the degree of white matter lucency, sulcal enlargement, and ventricular enlargement. Multi-infarct patients were divided into two groups: 1) index cases were defined as those with multi-infarct dementia as defined by the Diagnostic and Statistical Manual of Mental Disorders, edition 3 (DSM-III) criteria; and 2) control subjects were defined as those multi-infarct patients without dementia or multi-infarct dementia according to DSM-III criteria. RESULTS: Overall, multi-infarct index cases had more cerebral infarcts, more cortical and subcortical left hemisphere infarcts, higher mean ventricular volume to brain volume ratio, more extensive enlargement of the body of the lateral ventricles and cortical sulci, and a higher prevalence of white matter lucencies. Among multi-infarct cases and control subjects the most frequent site of infarction was the subcortical region, and the most frequent pattern of infarction was lacunar. Stepwise logistic regression analysis examined cranial computed tomography as well as other factors and showed that level of education, stroke severity, left cortical infarction, and diffuse enlargement of the left lateral ventricle were the best overall predictors of multi-infarct dementia. CONCLUSIONS: Level of education, stroke severity, and left hemisphere infarction may be predictors of multi-infarct dementia. PMID- 1595097 TI - Evaluation of vasomotor reactivity by transcranial Doppler and acetazolamide test before and after extracranial-intracranial bypass in patients with internal carotid artery occlusion. AB - BACKGROUND AND PURPOSE: The aim of this trial was to evaluate the effectiveness of extracranial-intracranial bypass with respect to vasomotor reactivity in patients with internal carotid artery occlusions and absent vasomotor reactivity, comparing them with a control group treated conservatively. METHODS: To test vasomotor reactivity in 104 patients with unilateral occlusion of the internal carotid artery, we measured blood flow velocity in the middle cerebral artery by transcranial Doppler sonography both at rest and after injection of acetazolamide. Among the 39 patients who failed to show increased mean blood flow velocity after the acetazolamide test distal to an occluded internal carotid artery by greater than or equal to 10%, 14 subjects subsequently underwent extracranial-intracranial bypass surgery (group A) and 14 age- and sex-matched subjects in whom no such procedure was done composed the control group (group B). Follow-up examinations were performed 3-6 months postoperatively and in the control group 3-6 months after initial examination. RESULTS: Baseline values of the mean blood flow velocity at rest on the affected side were reduced in both groups compared with the contralateral healthy side (group A, 46.0 +/- 15.1 cm/sec; group B, 48.1 +/- 16.7 cm/sec) and revealed only a marginal increase after acetazolamide. The contralateral side showed a normal blood flow velocity at rest and an adequate response to acetazolamide in both groups. On the follow up examination group A demonstrated a normalized vasodilatory capacity. Blood flow velocity increased significantly after acetazolamide from 41.9 +/- 13.1 cm/sec to 53.5 +/- 16.0 cm/sec (p less than 0.002). In group B, the compromised vasomotor reactivity remained unchanged. CONCLUSIONS: Our results demonstrate that transcranial Doppler sonography together with the acetazolamide test can identify subjects with reduced vasomotor reactivity distal to an occluded internal carotid artery, who may improve hemodynamically by an extracranial intracranial bypass. PMID- 1595098 TI - Prevalence of extracranial carotid artery disease detectable by echo-Doppler in an elderly population. AB - BACKGROUND AND PURPOSE: Little information is available on extracranial carotid artery disease in free-living elderly individuals. We sought to evaluate the prevalence of carotid lesions in the elderly. METHODS: Using echo-Doppler, we assessed the prevalence of possible atherosclerotic lesions in the internal carotid arteries (n = 478) and the external and common carotid arteries (n = 956) of 239 subjects 65-94 years of age living in retirement homes in Seattle, Wash. RESULTS: We found that 152 (31.8%) internal carotid arteries were affected by nonstenosing plaque and 37 arteries (7.7%) had stenosis or occlusion. In addition, 193 (20.2%) external or common carotid arteries showed nonstenosing plaques. There were 128 subjects (53.6%) with internal carotid disease, 106 (44.3%) with evidence of external or common carotid disease, and 75 (31.4%) affected by disease in all three sites. There were 80 subjects (33.5%) with no ultrasound evidence of carotid disease. We found that the presence and severity of carotid disease increased between the decades 65-74 and 75-84. We also demonstrated a positive association between systolic blood pressure and ultrasound evidence of carotid disease that was independent of age. CONCLUSIONS: The prevalence of extracranial artery disease in an apparently healthy population was high, although stenoses in most instances were not severe. We conclude that noninvasive ultrasound methods identify a relatively small fraction of individuals (5% of the total) at high risk for stroke or transient ischemic attack. Echo-Doppler might be used to monitor further disease progression and to evaluate the efficacy of different therapeutic or preventive interventions. PMID- 1595099 TI - Postprandial triglyceridemia and carotid atherosclerosis in middle-aged subjects. AB - BACKGROUND AND PURPOSE: It has been suggested that a postprandial accumulation of triglyceride-rich lipoproteins promotes the development of atherosclerosis. This study was designed to test the hypothesis that postprandial lipemia is independently associated with intima-media thickening of the extracranial carotid arteries. METHODS: Forty-seven middle-aged, moderately hypercholesterolemic individuals were recruited for a 1-day study of the lipemic response to a standard high-fat test meal. The formula was fed at a dose of 65 g fat/m2 body surface area, after a 14-hour fast, and blood was obtained for triglyceride analysis hourly for 8 hours. A baseline lipid profile was obtained. Each subject underwent a carotid ultrasound examination. The extent of alimentary lipemia (peak triglyceride response) was correlated with the carotid artery wall thickness as measured by B-mode ultrasound. RESULTS: Univariate analyses indicated an inverse correlation between peak triglyceride response and high density lipoprotein cholesterol concentration and a direct correlation with male sex, baseline triglyceride concentration, background fat intake, and waist-to-hip ratio. Of these, the only variable that showed a univariate correlation with B mode score was peak triglyceride response. Age and cigarette smoking were also correlated with B-mode score in univariate analyses. The correlation coefficient (r = 0.52) between peak triglyceride response to a fat-rich meal and B-mode score was significant (p less than 0.002) and remained so in multivariate analysis. Forward-selection stepwise regression resulted in the inclusion of only peak triglyceride response (p = 0.001) and smoking history (p = 0.005) as important predictors of carotid wall thickness in a linear model. CONCLUSIONS: The association between lipemic response and carotid wall thickness suggests that prolonged exposure of arterial wall cells to triglyceride-rich chylomicron remnants enhances the atherogenic process. PMID- 1595100 TI - Lifestyle factors and risk of cerebral infarction. AB - BACKGROUND AND PURPOSE: We evaluated the impact of lifestyle factors on the risk of ischemic stroke. METHODS: We used a nested case-control design. The cases comprised 163 persons (median age 69 years) admitted to a stroke unit and diagnosed with acute cerebral infarction. All cases had earlier participated in the North Trondelag Health Survey. The controls comprised 567 participants from the North Trondelag Health Survey, matched by sex and year of birth. RESULTS: Raised systolic (p less than 0.001) and diastolic (p = 0.02) blood pressure, antihypertensive treatment (p less than 0.001), previous myocardial infarction (p less than 0.001), prior stroke (p = 0.002), diabetes (p less than 0.001), and former daily smoking (p = 0.02) were identified as significant risk factors by univariate conditional logistic regression. No difference in risk was detected at different levels of alcohol consumption, salt intake, physical activity, or body mass index. Current smokers had virtually the same risk as nonsmokers. No association was found between stroke and the number of cigarettes smoked per day or the number of years of smoking. Multivariate conditional logistic regression identified diabetes (p = 0.002), raised systolic blood pressure (p less than 0.001), and former daily smoking (p = 0.01) as significant and independent risk factors. Previous myocardial infarction (p = 0.07), previous stroke (p = 0.1), and current daily smoking (p = 0.1) were of marginal significance. CONCLUSIONS: The established medical risk factors for stroke are confirmed. With the possible exception of smoking, we have not identified any lifestyle factor with a significant impact on the risk of ischemic stroke. PMID- 1595101 TI - Factors delaying hospital admission after stroke in Leicestershire. AB - BACKGROUND AND PURPOSE: Use of thrombolysis and acute treatments for cerebral infarction may require that acute stroke be treated as a medical emergency. To assess the factors influencing the time to admission in acute stroke, we conducted a prospective study of all such patients admitted to the hospitals in Leicester, UK, over a 12-month period. METHODS: Factors assessed were age, sex, time of stroke onset, stroke severity, home circumstances, and routes of admission. Initial between-group comparisons were made with the Mann-Whitney U test. The individual contribution of each of these variables was assessed with multiple linear regression analysis. RESULTS: An accurate time of stroke onset was identified in 374 (70%) of 535 registered patients (median age 77 [range, 29 98] years; 332 men, 203 women). Median time from onset to admission was 6 hours, with 25% of the patients arriving in less than 2.5 hours and 75% in less than 11.5 hours. Multiple regression confirmed that only admission through the bed allocation bureau (p less than 0.001), living alone (p less than 0.001), and nocturnal onset (p = 0.003) prolonged delay time. Despite patients over 70 years of age taking a median of 7 hours from onset to admission compared with 4 hours for those under age 70 (p less than 0.001), the effect of age appeared to be dependent on these three factors. Age, sex, level of consciousness, rural domicile, and place of admission did not influence the delay time independently. CONCLUSIONS: We have identified some of the factors affecting the hospital admission delay time for stroke. With the possible advent of effective early treatments for stroke, these factors will need to be addressed. PMID- 1595102 TI - Stroke and Parkinson's disease. AB - BACKGROUND AND PURPOSE: We sought to determine whether the recently reported decreased incidence of stroke and atherosclerotic disease in a university hospital-based Parkinson's disease patient population would be demonstrated in our patient population. METHODS: We performed a retrospective case-control review of the last 119 Parkinson's disease patients discharged from the Middleton Veterans Affairs Hospital Neurology Service to study the incidence of ischemic stroke, myocardial ischemia, tobacco use, and other stroke risk factors. Controls were age and sex matched and were randomly taken from 238 non-Parkinson's disease discharges in which stroke or myocardial infarction was not the reason for hospitalization. RESULTS: The cumulative incidences of ischemic stroke, hypertension, and diabetes mellitus were not significantly different between groups. Myocardial infarction, coronary artery disease, tobacco use, atrial fibrillation, cancer, and ethanol abuse were significantly more prevalent in the controls, whereas dementia and congestive heart failure were the only variables studied that were more prevalent in the Parkinson's disease patients. CONCLUSIONS: Our study failed to demonstrate that Parkinson's disease patients from a Veteran population were protected from ischemic stroke. PMID- 1595103 TI - Histopathological analysis of the mechanisms of intracranial hemorrhage complicating infective endocarditis. AB - BACKGROUND AND PURPOSE: We conducted the present study to elucidate the pathological mechanisms leading to intracranial hemorrhage complicating infective endocarditis. METHODS: Neurological, neuroradiological, and histopathological analyses were performed in 16 patients (one surgical and 15 autopsy cases), 12 men and four women 26-68 years of age, who had demonstrated central nervous system complications during the course of infective endocarditis. RESULTS: Intracranial hemorrhage was found in all cases; parenchymal hematomas were found in 12 cases, hemorrhagic infarcts in four cases, and primary subarachnoid hemorrhages in two cases. Chronological analysis of neurological examination and computed tomographic scan of the brain confirmed that antecedent cerebral ischemic events had occurred in five of 12 patients showing parenchymal hematomas at autopsy. Hemorrhagic infarct, indicated by petechial or diffuse hemorrhages within the infarct, was seen in another four patients, so that hemorrhagic transformation of the ischemic infarct was confirmed in nine patients. Although mycotic aneurysms were found in five patients, only three of these were ruptured; the other two were occluded with septic emboli. Pyogenic arteritis without aneurysm was found to be distributed in the small cortical arterial branches located in the spaces of cortical sulci, with rupture occurring in five patients. CONCLUSIONS: These results suggest that hemorrhagic transformation of the ischemic infarct due to septic emboli is the most frequent mechanism leading to intracerebral hemorrhage encountered in patients dying of infective endocarditis and that rupture of pyogenic arteritis may be responsible for such hemorrhage in many cases, with ruptures of mycotic aneurysms as an alternative mechanism. PMID- 1595104 TI - European stroke prevention study: effectiveness of antiplatelet therapy in diabetic patients in secondary prevention of stroke. AB - BACKGROUND AND PURPOSE: The European Stroke Prevention Study was a multicenter trial comparing the effect of a combination of 75 mg dipyridamole and 330 mg acetylsalicylic acid three times a day with the effect of a placebo in the prevention of stroke or death in 1,861 patients after one or more episodes of recent transient ischemic attack or cerebral infarction. METHODS: The present study represents a secondary analysis of the efficacy of study medication in diabetic (n = 216) and nondiabetic (n = 1,645) patients. RESULTS: The risk of end point events was greater in diabetic than in nondiabetic subjects. Total end point reduction in individuals receiving the combination of dipyridamole and acetylsalicylic acid was 39% in nondiabetic subjects and 23% in diabetic subjects in the explanatory analysis, and the reduction in the risk of stroke was 48% and 32%, respectively. However, a statistically significant reduction of risk was obtained only in nondiabetic subjects. CONCLUSIONS: The combination of dipyridamole and acetylsalicylic acid appeared to be more effective in nondiabetic subjects than in diabetic subjects in the prevention of death and stroke although the low number of diabetic patients may at least in part explain this result. PMID- 1595105 TI - Hemodynamic and metabolic changes in crossed cerebellar hypoperfusion. AB - BACKGROUND AND PURPOSE: The pathophysiology of crossed cerebellar diaschisis remains to be elucidated. The mechanism responsible appears to be deafferentation through the corticopontocerebellar tract, which terminates in the cerebellar gray matter. However, few studies have demonstrated the hemodynamic and metabolic changes in the cerebellar gray matter and pons in crossed cerebellar diaschisis. METHODS: Using positron emission tomography in 24 patients with unilateral supratentorial stroke, we evaluated regional blood flow, metabolic rate of oxygen, oxygen extraction fraction, and blood volume in the cerebellar cortex and pons. Sixteen patients with significant cerebellar blood flow asymmetry, defined as a percentage difference in blood flow beyond the upper 95% confidence limit defined in eight normal subjects, were selected as the group with crossed cerebellar hypoperfusion. RESULTS: In patients with crossed cerebellar hypoperfusion, the metabolic rate of oxygen was significantly decreased in the cerebellar cortex contralateral to the supratentorial stroke, compared with that in the ipsilateral cerebellar cortex; this decrease was less than the decrease in cerebellar blood flow. The degrees of cerebellar asymmetry in these two parameters were negatively correlated with the metabolic rate of oxygen in the pons. The oxygen extraction fraction was slightly, but significantly, increased. In contrast to the ischemic state, however, the cerebellar blood volume was decreased, with no difference in the ratio of cerebellar blood flow to blood volume. CONCLUSIONS: These findings support interruption of the corticopontocerebellar tract as the mechanism of crossed cerebellar hypoperfusion. Our results also suggest a mild elevation in the oxygen extraction fraction in this state, with a mechanism distinct from ischemia. PMID- 1595106 TI - Cerebroprotective effect of a non-N-methyl-D-aspartate antagonist, GYKI 52466, after focal ischemia in the rat. AB - BACKGROUND AND PURPOSE: Cerebroprotection after the administration of N-methyl-D aspartate antagonists has been well documented. The present study sought to determine whether a cerebroprotective effect could be achieved with the administration of a non-N-methyl-D-aspartate antagonist, GYKI 52466 (1-(4 aminophenyl)-4-methyl-7,8-methylene-dioxy-5H-2,3-benzodiazep ine hydrochloride; molecular weight, 330) after middle cerebral artery occlusion in the rat. METHODS: Neurological deficit and infarct volume 24 hours after permanent left middle cerebral artery occlusion in Fischer rats (n = 7-13 per group per dose) were studied. Cerebral infarcts was visualized by the lack of reduction of 2,3,5 triphenyltetrazolium chloride. RESULTS: GYKI 52466 (10 mg.kg-1 i.p. at 0, 2, 4 hours) after middle cerebral artery occlusion had no effect on infarct volume. GYKI 52466 (10 mg.kg-1 i.v. for 5 minutes followed by 15 mg.kg-1.hr-1 i.v. for 2 hours immediately after middle cerebral artery occlusion reduced cortical infarct volume by 68% (from 69 mm3 in vehicle-treated to 22 mm3 in GYKI 52466-treated animals; p less than 0.05). A 1-hour delay before initiation of drug infusion resulted in a 48% reduction in cortical infarct volume (from 60 mm3 vehicle treated rats to 31 mm3 in GYKI 52466-treated rats; p less than 0.05). A 2-hour delay before initiation of drug infusion had no effect on cortical infarct volume. Neurological deficits (with blinded assessment after 24 hours) were improved after immediate treatment and after delayed treatment (1 or 2 hours). CONCLUSIONS: The cerebroprotective effect of GYKI 52466 in the rat suggests a possible therapeutic role for non-N-methyl-D-aspartate antagonists given shortly after the onset of stroke. PMID- 1595107 TI - Brain and tissue distribution of polyethylene glycol-conjugated superoxide dismutase in rats. AB - BACKGROUND AND PURPOSE: The purpose of this study was to determine the distribution of polyethylene glycol-conjugated superoxide dismutase in the brain, cerebrospinal fluid, and various organs. METHODS: Distribution of iodine-125 labeled polyethylene glycol-conjugated superoxide dismutase was determined in three groups of male Sprague-Dawley rats: a normotensive sham control group (n = 9) and groups given 125I-labeled polyethylene glycol-conjugated superoxide dismutase either 30 minutes before (n = 10) or 30 minutes after (n = 7) norepinephrine-induced hypertensive injury. RESULTS: In the first 30 minutes after intravenous administration, polyethylene glycol-conjugated superoxide dismutase plasma activity declined to 70% of the initial value and then decreased negligibly between 30 and 90 minutes. Levels of 125I-labeled polyethylene glycol conjugated superoxide dismutase in normotensive animals were low in the brain and cerebrospinal fluid and highest in kidney. Brain levels of polyethylene glycol conjugated superoxide dismutase were elevated only in those rats that received it before hypertensive injury; however, cerebrospinal fluid levels were elevated in animals receiving the drug either before or after hypertensive injury. CONCLUSION: Our results suggest that the blood-brain barrier becomes more permeable to polyethylene glycol-conjugated superoxide dismutase only during the hypertensive period but that the blood-cerebrospinal fluid barrier sustains more permanent injury. We suggest that the therapeutic effectiveness of polyethylene glycol-conjugated superoxide dismutase in hypertensive brain injury is due to its action in the vascular wall or to its extracellular activity in the cerebrospinal fluid. PMID- 1595108 TI - Serotonin release into plasma during common carotid artery thrombosis in rats. AB - BACKGROUND AND PURPOSE: We have tested the hypothesis that platelet-derived serotonin is released into the bloodstream during cerebrovascular thrombosis. METHODS: Nonocclusive common carotid artery thrombosis was produced photochemically in 22 anesthetized adult male Wistar rats using the photosensitizing dye rose bengal and irradiation with an argon-pumped dye laser. Plasma serotonin levels were recorded before, during, and after photothrombosis by intra-arterial in vivo microdialysis with the probe placed distal to the site of thrombosis. RESULTS: During and immediately after the common carotid artery thrombosis, serotonin levels increased significantly to a peak value of 781 nmol/l (p less than 0.001 by analysis of variance), representing a 15-fold increase compared with baseline levels. The increased serotonin levels gradually decreased but remained significantly elevated for 90 minutes. Ultrastructural analysis of the carotid thrombi identified a dense mass of aggregated platelets at various stages of degranulation. CONCLUSIONS: These results are the first to demonstrate directly that serotonin accumulation occurs in plasma during and after the acute phase of common carotid artery thrombosis. Increased plasma serotonin levels may play a major role in the cerebral blood flow and blood-brain barrier abnormalities previously documented in this model of large-vessel thrombotic stroke. PMID- 1595109 TI - Influence of tissue plasminogen activator and heparin on cerebral ischemia in a rabbit model. AB - BACKGROUND AND PURPOSE: The aims of this study were to verify that tissue-type plasminogen activator given either 1 or 2 hours after experimental embolic stroke in rabbits diminishes the volume of resulting ischemic brain and to ascertain the effect of the simultaneous administration of heparin. METHODS: We embolized the middle cerebral artery of rabbits by injecting performed autologous arterial ("white") thrombus into one internal carotid artery. Treatment with 2 mg/kg tissue-type plasminogen activator, alone or in combination with heparin, was commenced either 1 or 2 hours after embolization. The animals were killed 5 hours after treatment commenced, and their brains were examined for evidence of ischemia and hemorrhage. RESULTS: Administration of tissue-type plasminogen activator significantly diminished the size of the resulting brain ischemia. Administration of heparin, with or instead of tissue-type plasminogen activator, did not result in a significant decrease in the volume of cerebral ischemia, but it also did not lead to hemorrhagic transformation of the stroke. CONCLUSIONS: In the rabbit model, administration of tissue-type plasminogen activator within 2 hours diminished the volume of brain rendered acutely ischemic by embolic stroke. Since the simultaneous administration of heparin during this same period did not result in any instances of hemorrhagic transformation, tissue-type plasminogen activator may have some place for use in such circumstances to mitigate a tendency to further embolic or thrombotic events. PMID- 1595110 TI - Effects of hypothermia on evoked potentials, magnetic resonance imaging, and blood flow in focal ischemia in rabbits. AB - BACKGROUND AND PURPOSE: Mild hypothermia has been shown to ameliorate neuronal damage due to cerebral ischemia. In our study, the influence of mild-to-moderate hypothermia was examined in a rabbit model of focal cerebral ischemia. METHODS: After 4 hours of permanent ischemia induced by occlusion of the anterior and middle cerebral and internal carotid arteries, somatosensory evoked potentials and regional cerebral blood flow were measured. Ex vivo magnetic resonance imaging scans were also obtained to determine the degree of ischemic brain injury. Three temperature (temporalis muscle) groups were studied: 37 degrees C, 33 degrees C, and 30 degrees C (n = 5 per group). An additional two animals were used to confirm that temporalis muscle temperatures were well correlated with brain temperature. Rectal temperatures were kept constant (37.5 degrees C) in all groups. RESULTS: After 4 hours of focal ischemia, evoked potentials in the normothermic animals remained depressed (2.2 +/- 2.1% [mean +/- SEM] preocclusion values). Recovery of potentials was significantly enhanced in both hypothermic groups (p less than 0.05): 18.2 +/- 6.5% (33 degrees C) and 43.6 +/- 12.2% (30 degrees C). Quantitative magnetic resonance measurements showed that T1 and T2 relaxation times were increased in the core ischemic regions within the cortex (20.4 +/- 4.0% and 25.3 +/- 5.9%, respectively). These elevations in T1 and T2 were reduced by hypothermia. However, blood flow was not improved by lowered temperature; in fact, flow in the 30 degrees C group was significantly decreased compared with the other groups (p less than 0.01). There was no statistically significant correlation between specific cerebral blood flow values and T1 or T2 elevations. CONCLUSIONS: These results demonstrate that hypothermia can improve evoked potentials and magnetic resonance parameters in permanent focal ischemia. However, moderate hypothermia (30 degrees C) appears to also significantly decrease blood flow in the ischemic brain. PMID- 1595111 TI - Tirilazad reduces cortical infarction after transient but not permanent focal cerebral ischemia in rats. AB - BACKGROUND AND PURPOSE: We examined the cytoprotective effect of the lipid peroxidation inhibitor tirilazad mesylate (U74006F) in rodent models of neocortical infarction induced by transient and permanent focal cerebral ischemia. METHODS: Wistar rats (experiment 1) and spontaneously hypertensive rats (experiment 2) were subjected to 2 hours of transient middle cerebral artery occlusion followed by 22 hours of reperfusion and pretreated with 10 mg/kg i.p. tirilazad, vehicle, or saline. Repeat doses were given at 4 and 10 hours after reperfusion. Spontaneously hypertensive rats were also subjected to permanent middle cerebral artery occlusion and either pretreated with tirilazad, vehicle, or saline intraperitoneally (experiment 3) or treated with either tirilazad or vehicle intravenously after ischemia (experiment 4). Cortical infarct volumes were measured 24 hours after the onset of either transient or permanent ischemia, and changes in core regional cerebral blood flow were monitored with laser Doppler flowmetry. RESULTS: Tirilazad reduced infarct volume after transient ischemia by 40% in Wistar rats (p = 0.08) (experiment 1) and 23% in spontaneously hypertensive rats (p less than 0.05) (experiment 2) but did not reduce infarction after permanent ischemia whether it was given intraperitoneally (experiment 3) or intravenously (experiment 4). Ischemic core blood flows were not affected during ischemia, nor were they affected during reperfusion after transient ischemia. CONCLUSIONS: Tirilazad reduces cortical infarction in transient but not permanent ischemia, an effect not related to improvement in regional cerebral blood flow. Tirilazad might prove to be useful as an adjuvant therapy after successful thrombolysis in acute stroke patients. PMID- 1595112 TI - Concomitants of asymptomatic retinal cholesterol emboli. AB - BACKGROUND AND PURPOSE: Asymptomatic retinal cholesterol emboli are sometimes encountered on ophthalmoscopic examination. They are associated with decreased survival, but their clinical significance is not fully known. We sought to determine which vascular risk factors are associated with such emboli. METHODS: We studied 70 consecutive men (55-84 years old) with asymptomatic retinal cholesterol emboli diagnosed in an eye clinic. Twenty-one men (57-78 years old) from the same eye clinic without retinal emboli or retinal ischemic events were randomly selected as control subjects. We determined vascular risk factors, presence of ischemic heart disease, and extracranial carotid artery disease. RESULTS: Patients had a higher prevalence of hypertension, smoked more, and had a higher prevalence of heterogeneous or echolucent carotid plaques on either side than did control subjects (p less than 0.001 for all three factors). Patients also had a higher prevalence of carotid artery stenosis greater than or equal to 50% on either side and a higher prevalence of ischemic heart disease than did control subjects, but these did not reach statistical significance (p = 0.06 and p = 0.08, respectively). CONCLUSIONS: Our findings suggest that hypertension and cigarette smoking may be important in the pathogenesis of asymptomatic retinal cholesterol emboli and that these emboli indicate systemic atherosclerosis rather than ipsilateral carotid artery stenosis. PMID- 1595113 TI - Small infarctions of cochlear, retinal, and encephalic tissue in young women. AB - BACKGROUND AND PURPOSE: Recently, a rare syndrome that involves uniformly the brain, inner ear, and retina in previously healthy young women has been described. Brain biopsies and ophthalmologic examinations disclosed small infarcts as a pathoanatomical substrate of the disease. In previous reports, an autoimmune disorder or a coagulopathy have been suggested as possible etiologies. CASE DESCRIPTIONS: Both patients (aged 22 and 20 years) had brain involvement with neurological and neuropsychological deficits. Multifocal small hyperintensities were shown in magnetic resonance imaging of the brain. Findings of cerebrospinal fluid examination and electroencephalography were pathological in case 1 and of cerebral angiography in case 2. Both patients had a neurosensory hearing loss and multiple retinal branch arteriolar occlusions. Both women were on fenfluramine before onset of the disease. In case 1, attacks recurred during a follow-up of 34 months. At onset of the disease the 5-hydroxyindoleacetic acid and homovanillic acid levels of the cerebrospinal fluid were reduced; 13 months later the 5-hydroxyindoleacetic acid level was still reduced and the homovanillic acid level was low-normal. In case 2, with the longest follow-up of 13 years, the disease was active during only the initial 2 1/4 years. During this period a combination of oral anticoagulant and antiplatelet agents was ineffective. CONCLUSIONS: Our findings could not support current etiologic hypotheses. Whether changes in 5-hydroxyindoleacetic acid and homovanillic acid levels in the cerebrospinal fluid and/or fenfluramine intake play a role in the pathogenesis of the disease remains to be elucidated. PMID- 1595114 TI - Stroke after pituitary irradiation. AB - BACKGROUND AND PURPOSE: Cranial irradiation may lead to accelerated atherosclerosis over several years. Stroke has been described after cranial irradiation administered for a number of conditions. However, pituitary irradiation has only rarely been associated with stroke. CASE DESCRIPTIONS: Two patients, 39 and 46 years of age, suffered strokes 13 and 20 years, respectively, after irradiation for pituitary tumors. Strokes were in the territories of small perforating arteries, but large vessels such as the carotid siphon and anterior cerebral arteries were also abnormal. Other risk factors for stroke were absent. CONCLUSIONS: It is suggested that pituitary irradiation increases the risk of subsequent stroke due to the known effects of ionizing radiation on vascular walls. PMID- 1595115 TI - Role of ticlopidine for prevention of stroke. AB - BACKGROUND: Ticlopidine, an antiplatelet agent with a unique mechanism of action, is now available for clinical use in the United States and Canada. SUMMARY OF COMMENT: Recently two large randomized trials demonstrated that ticlopidine can reduce the risk of subsequent stroke in patients presenting with a transient ischemic attack or stroke. One study found that ticlopidine was more effective than aspirin for stroke prevention; however, it was less well tolerated than aspirin and was associated with severe but reversible neutropenia in almost 1% of patients. CONCLUSIONS: Ticlopidine is effective for both primary and secondary stroke prevention. It has a favorable risk/benefit ratio and is a particularly attractive option for patients who are unable to take aspirin. PMID- 1595116 TI - The CASANOVA study: immediate surgery versus delayed surgery for moderate carotid artery stenosis? PMID- 1595117 TI - The NIH stroke scale and the FIM in stroke rehabilitation. PMID- 1595118 TI - The syndrome of Babinski and Nageotte. PMID- 1595119 TI - Glycemia in the first stage after stroke: nutritional and fluid therapy influence. PMID- 1595120 TI - Occipitoatlantal instability: a hemodynamic cause of vertebrobasilar ischemia after neck motion. PMID- 1595121 TI - Nephrotic syndrome, accelerated atherosclerosis, and stroke. PMID- 1595122 TI - Thrombotic thrombocytopenic purpura associated with ticlopidine. PMID- 1595123 TI - Structure of growth hormone and its receptor: an unexpected stoichiometry. PMID- 1595124 TI - Valine is a precursor of propionyl-CoA. AB - For some time the metabolism of valine has been misrepresented by several biochemistry textbooks. This article demonstrates that propionyl-CoA occurs as an intermediate in the valine metabolic pathway before the formation of methylmalonyl CoA. PMID- 1595125 TI - A bipartite nuclear targeting motif in protein kinase C? PMID- 1595126 TI - Communication among the proteoglycans. PMID- 1595127 TI - Flavin-linked peroxide reductases: protein-sulfenic acids and the oxidative stress response. AB - Sequence analyses of the Streptococcus faecalis NADH peroxidase and the flavoprotein component of the Salmonella typhimurium alkyl hydroperoxide reductase indicate clear evolutionary links with members of the flavoprotein disulfide reductase family. However, chemical and spectroscopic evidence demonstrate that the non-flavin redox center in NADH peroxidase is an unusual stabilized cysteine-sulfenic acid (Cys-SOH) derivative, and not a cystine disulfide as found in the disulfide reductases. This redox-active element, when appropriately stabilized by the respective protein environment, appears to play key roles in both the catalytic and regulatory aspects of the bacterial response to oxidative stress. PMID- 1595128 TI - Chromatin dynamics and the modulation of genetic activity. AB - Chromatin, the genetic material of eukaryotes, is a dynamic macromolecular assembly that continuously changes its composition and conformation to accommodate different stages of genetic activity, e.g. transcription and replication. Evidence is accumulating that the dynamic behavior of chromatin has important functional roles in the modulation of genetic activity, largely due to the intrinsic properties of arrays of nucleosome cores. PMID- 1595129 TI - Complex regulation of simple sugar transport in insulin-responsive cells. AB - Facilitated sugar entry into mammalian cells is catalysed by multiple isoforms of the glucose transporter and regulated by hormonal stimuli, nutritional status and oncogenesis. A large reserve of latent glucose transport capacity must be maintained by muscle and adipose cells that are sensitive to insulin, the primary activator of sugar uptake after feeding. Intracellular sequestration of sugar transporters accounts for a large part of this latent capacity, but new findings suggest that there is also reversible suppression of intrinsic catalytic activity of those glucose transporters residing at the cell surface. The mechanism of this suppression appears to be occlusion or disruption of the exofacial sugar-binding sites on the glucose-transporter proteins. PMID- 1595130 TI - The early development of neurosonology: II. Fetal and neonatal echoencephalography. AB - The obscuring effect of the diploe in the skull for attempts to use ultrasonic energy to image the brain is not present in the fetus, neonate or infant prior to ossification of the skull. Initially, however, the fetal examination was largely confined to a single measurement of the size of the skull, usually in the bi parietal plane, just prior to labour. In this way it became possible to identify immature fetuses where delivery should be delayed as long as possible, as well as cases of cephalo-pelvic disproportion where the large size of the fetal head would make vaginal delivery difficult. Measurements made earlier in pregnancy, in order to predict the gestational age and estimated date of delivery, would only be accurate if all fetal heads were the same size at every gestational age. Similarly, attempts to predict birthweight from the size of the fetal head at any given gestational age foundered both upon the uncertainty of determining the gestational age from the menstrual history and upon the variations in the size of fetuses for various gestational ages. By making serial measurements of fetal head size, the rate of fetal growth can be measured. In this way, it is possible to separate the normal fetus which appeared to be small for its gestational age because the gestational age had been erroneously calculated from the menstrual history, from two clinically important groups. In the first group, the fetus is small and grows abnormally slowly throughout the whole pregnancy because of some congenital defect; and in the second the rate of growth becomes slowed towards the end of pregnancy because the placenta is no longer able to supply the increased nutritional needs of the mature fetus. Where it is not possible to make serial measurements throughout pregnancy, they can often be restricted to two measurements. The first is made in mid-pregnancy and, if the size of the fetal head agrees with that predicted from the menstrual history, it is assumed that the fetus is not abnormally small due to some congenital defect. In such cases the only other examination that needs to be made is another measurement near term to identify cases of placental insufficiency. If the first measurement does not coincide with that expected from the menstrual history, then more frequent measurements should be made in order to separate those normal fetuses in which the gestational age was wrongly calculated from the menstrual history from those fetuses with growth retardation throughout pregnancy due to some abnormality.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1595131 TI - Differentiation of normal and ischemic right ventricular myocardium with quantitative two-dimensional integrated backscatter imaging. AB - We have previously shown that ultrasonic tissue characterization with two dimensional (2D) guided M-Mode acquisition of integrated backscatter (IB) identifies ischemic and infarcted myocardium. However, there is no information regarding the applicability of IB in assessment of right ventricular (RV) myocardial acoustic properties. Thus, we performed IB imaging of the RV in a group of 45 consecutive patients and were successful in 16, all of whom had normal RV wall motion. This group was compared to 8 additional patients studied acutely with clinical criteria of RV infarction. Real-time IB from RV was obtained from parasternal long axis or subcostal views. Diastolic-to-systolic cyclic variation of IB in normals was 4.8 +/- 0.9 dB (+/- SD). No significant difference was observed between parasternal and subcostal views (5.2 +/- 0.8 and 4.5 +/- 0.9 dB). Mean value of delay (R wave to nadir of backscatter normalized to the electrocardiographic Q-T interval) was 0.85 +/- 0.07. Patients with RV infarction had significantly lower values averaging 3.2 +/- 0.8 dB (p less than 0.001 vs. normals); cyclic variation of IB was present in all despite severe hypokinesis in 4/8. Mean value of normalized delay was 0.80 +/- 0.04 and was not different from normals. Thus, tissue characterization provides quantitative information regarding RV myocardial structure and function. Preservation of IB cyclic variation in patients with RV infarction suggests residual RV myocardial viability. PMID- 1595132 TI - Factors determining aortic and umbilical blood flow pulsatility in fetal sheep. AB - The link between the flow pulsatility index (P.I.) and vascular resistance was examined by infusing vasoactive agents or by progressive embolization of the peripheral vascular bed. Experiments were performed on fetal sheep near term, 3 days after implantation of a flow probe, catheter-tip pressure transducers, and fluid-filled catheters to monitor hemodynamics in the umbilical artery and the descending thoracic aorta. Increasing placental and hind limb resistance by embolization with microspheres caused a progressive increase in flow P.I. whereas altering resistance with vasoactive agents had variable results. Results showed that flow P.I. was sensitive to impedance to pulsatile flow and pressure pulsatility in addition to vascular resistance. We conclude it is hazardous to use the flow P.I. to detect changes in vascular resistance particularly when these changes are induced by physiological adjustments or vasoactive agents. PMID- 1595133 TI - Acoustic emission and sonoluminescence due to cavitation at the beam focus of an electrohydraulic shock wave lithotripter. AB - The acoustic emission from cavitation in the field of an extracorporeal shock wave lithotripter has been studied using a lead zirconate titanate piezoceramic (PC4) hydrophone in the form of a 100-mm diameter focused bowl of 120-mm focal length. With this hydrophone directed at the beam focus of an electrohydraulic lithotripter radiating into water, it is possible to identify signals well above the noise level, at the 1-MHz resonance of the hydrophone, which originate at the beam focus. Light emission, attributed to sonoluminescence, is also shown to originate at the focal region of the lithotripter, and the signal obtained from a fast photomultiplier tube directed at the focus has similarities in structure and timing to the detected acoustic signals. The multiple shock emission resulting from a single discharge of an electrohydraulic source is shown to result in two separate bursts of cavitational activity separated by a period of 3-4 ms. The signal burst corresponding to the primary shock has a duration of about 600 microseconds with little noticeable structure. The signal burst associated with the secondary shock has a reproducible structure with two distinct peaks separated by about 200 microseconds depending on the shock amplitude. THe timing and structure of each burst is shown to be in reasonable agreement with the theoretical predictions made by Church (1989) based on the Gilmore model of bubble dynamics. In particular, it is shown that it is possible to obtain precise measurements of the time delay between the separate peaks within the signal burst detected following the secondary shock and this may, as predicted, provide a method of determining the size of bubbles remaining after the primary shock. PMID- 1595134 TI - On the feasibility of pulse-echo speed of sound estimation in small regions: simulation studies. AB - Computer simulations are used to study the feasibility of the estimation of sound speed in small regions with precision better than 1% using the Beam Tracking method. The speed of sound is estimated in a 10-mm by 10-mm region by considering a number of parallel tracks confined to the small region. The transducer focusing and the step sizes for the tracking and tracked transducers required to extract the maximum amount of uncorrelated data from the 10-mm by 10-mm region is evaluated. The results show that the speed of sound can be estimated with error less than 1% in a small region using a typical medical transducer. The statistical comparison of estimates in small areas with different speed of sound is also considered. PMID- 1595135 TI - Temperature rise generated by a focussed Gaussian beam in a two-layer medium. AB - The temperature rise is calculated at points along the axis of a focussed Gaussian beam propagating through a two-layer medium; the first layer is non attenuating and the second one consists of absorbing material simulating soft tissue. This two-layer medium is relevant to several situations encountered in medical applications of diagnostic ultrasound. These include fetal examinations via the abdominal wall, where the beam may travel a significant distance through urine or amniotic fluid before reaching the fetus. PMID- 1595136 TI - Sonic velocity and attenuation in wet compact cow femur for the frequency range 5 to 100 MHz. AB - Ultrasonic studies on bone have not been done as intensively as other tissues, probably because there is less opportunity to examine bone in vivo by this modality. There is considerable interest in using ultrasonics to learn about the material properties of bone for which purpose the sonic spectrum may be useful. The longitudinal sonic velocity and attenuation have been found for several sections from one sample of wet cow femur for both the axial and radial directions over the frequency range of 5 to 100 MHz. The basic technique was solid-to-solid contact using a fused quartz buffer rod coupled to the bone specimen. There is clear evidence of velocity dispersion which Lakes et al. (1986) did not find over a frequency range up to 16 MHz. While there seems to be a peak in both velocity and attenuation at 70 MHz, it is necessary to obtain measurements at higher frequencies to make sure this is not an artifact. The axial sonic velocity varied from 4.29 km/s at 5 MHz to 4.447 km/s at 50 MHz, while the radial velocity was 3.45 km/s at 5 MHz and increased to 3.62 km/s at 50 MHz. The attenuation coefficient axially started at a mean value of 3.5 db/mm at 5 MHz and increased to a mean of 19 db/mm at 100 MHz. The corresponding radial attenuation coefficients are 5.2 and 26, respectively. PMID- 1595137 TI - Measures of cardiac output. PMID- 1595138 TI - Comparison of two recompression profiles in treating experimental cerebral air embolism. AB - The standard treatment for cerebral arterial gas embolism (CAGE) is an initial recompression to 6 atm abs on air for 30 min followed by oxygen breathing at 2.8 and 1.9 atm abs. It has been suggested that initial recompression to 2.8 atm abs on O2 may be as beneficial, thus avoiding potential treatment complications associated with the deeper depth. To test this hypothesis, we measured the recovery of the somatosensory evoked potential (SEP) following air embolism in anesthetized, ventilated cats. Air was infused into the carotid artery in increments of 0.08 ml until the SEP amplitude was reduced to less than 10% of the baseline value for 15 min. Three groups were studied. A control group (n = 10) received no further treatment after SEP suppression. The second group (6 atm abs/HBO] (n = 8) was compressed to 6 atm abs on air for 30 min followed by O2 breathing at 2.8 atm abs for 100 min. The third group (HBO) (n = 8) was compressed to 2.8 atm abs on O2 for 130 min. The control group recovered 28.8 +/- 18.2% (mean +/- SD) of the baseline amplitude, whereas the 6 atm abs/HBO group recovered 48.6 +/- 22.6%, and the HBO group recovered 62.0 +/- 20.3%. An analysis of variance revealed that only the HBO group had significantly (P less than 0.01) better recovery than the control group. There was no significant difference in SEP recovery between the 2 treatment groups. These results suggest that treating CAGE at 2.8 atm abs with O2 is a viable alternative to the current therapy. PMID- 1595139 TI - Lidocaine as an adjunct to hyperbaric therapy in decompression illness: a case report. AB - A recreational scuba diver with nervous system decompression illness had a poor response to hyperbaric therapy. On the basis of available and supportive in vivo data, he was then given a continuous infusion of lidocaine (serum levels, low therapeutic range: 6.4-9.1 mumol/liter). Within 24 h of the start of this infusion he experienced a full resolution of his neurologic deficits. His symptoms recurred 3 days later, but again completely resolved after further hyperbaric therapy and concurrent administration of lidocaine (serum levels: 6.9 9.1 mumol/liter). This observation supports the need to conduct trials of lidocaine as an adjunct to hyperbaric therapy in decompression illness. PMID- 1595140 TI - Radiofrequency energy for rewarming of cold extremities. AB - Radiofrequency (RF) coils, developed to resonate at 27.12 MHz, were evaluated for effectiveness in rewarming thermally unprotected extremities of 5 male subjects. Bare hands or bare feet were exposed to 10.0 degrees C air during a total of four exposures for each subject. Deposition of RF energy for two of the exposures (one for the hands and one for the feet) began when a predetermined surface skin temperature was achieved. Rewarming continued for 10 min while fiber-optic sensors recorded surface skin temperatures at eight locations for each hand and four locations for each foot. Results were compared to data from identical exposures but without RF rewarming. Statistically significant (P less than 0.01) warming occurred at all of the monitored locations. Our results clearly demonstrate the ability of RF energy to warm hands and feet in cold environments. PMID- 1595141 TI - Microbiologic hazards for inhabitants of deep diving hyperbaric complexes. PMID- 1595142 TI - Simulation of a microbial epidemic on a diving ship. PMID- 1595143 TI - Decompression sickness risk in women. PMID- 1595144 TI - Program and abstracts. Undersea and Hyperbaric Medical Society annual scientific meeting. 23-27 June 1992, Bethesda, Maryland. PMID- 1595145 TI - Effect of body position on intravesical pressure in the anaesthetised bitch. AB - The position adopted by 50 recumbent dogs was recorded while they were sleeping or resting; the commonest orientation of their hindquarters was right lateral recumbency. The intravesical pressure in the urinary bladder of 24 anaesthetised bitches lying in right lateral recumbency was compared with the intravesical pressure recorded when the same bitches were supported in a standing position. The intravesical pressure was significantly higher when the bitches were in right lateral recumbency (P less than 0.001) and the difference was unaffected by whether they were continent or not, and had no significant correlation with bodyweight. These findings help to explain why bitches with an incompetent urethral sphincter mechanism tend to leak predominantly when they are recumbent. PMID- 1595146 TI - Canine distemper infection associated with acute nervous signs in dogs. AB - Eight vaccinated dogs suddenly developed progressive ataxia, paresis or paralysis of short duration. A histopathological examination revealed a non-suppurative meningoencephalitis suggestive of a viral infection, and immunohistochemical examination confirmed the presence of canine distemper virus antigen in five of the dogs. Distemper had not been suspected from the clinical examination of the dogs. PMID- 1595147 TI - A comparison of hemilaminectomy (with concomitant disc fenestration) and dorsal laminectomy for the treatment of thoracolumbar disc protrusion in dogs. AB - The techniques of hemilaminectomy (with concomitant disc fenestration) and dorsal laminectomy were compared statistically in two groups of 30 dogs with thoracolumbar disc disease. On presentation all the dogs were unable to walk and were graded 1 to 3 according to their degree of neurological dysfunction. Nineteen had a previous history of thoracolumbar pain or hindlimb paresis. Radiography showed a narrowed disc space or extruded calcified disc material in 52 of the dogs and lumbar myelography revealed an extradural mass in 57; 24 of the dogs had clinical or myelographic lateralisation of signs. Hemilaminectomy significantly improved the ability to retrieve protruded disc material compared with dorsal laminectomy, and the removal of protruded disc material significantly improved the degree of recovery. Fenestration significantly reduced the recurrence of thoracolumbar disc disease. PMID- 1595148 TI - Fatal canine neurotoxicosis attributed to blue-green algae (cyanobacteria). PMID- 1595149 TI - 'Spasticity' in the Devon rex cat. PMID- 1595150 TI - Prevalence of mitral valve insufficiency in cavalier King Charles spaniels. PMID- 1595151 TI - Population sizes and frequency of staphylococci at mucocutaneous sites on healthy dogs. PMID- 1595152 TI - Embryo transfer legislation. PMID- 1595154 TI - Drug combination side effects. PMID- 1595153 TI - Transport of food animals. PMID- 1595155 TI - Ivermectin in guinea pigs. PMID- 1595156 TI - Unusual poisoning in a dog. PMID- 1595157 TI - Intrapericardial heterotopic liver in a cat. PMID- 1595159 TI - Contact with oestrous female pigs stimulates and synchronises puberty in gilts. AB - Three experiments, using a total of 132 pre-pubertal gilts, were carried out to investigate the influence of contact with oestrous female pigs on the attainment of puberty by gilts. Experiment 1 compared the effect of removing the gilts from their groups as they reached puberty in response to exposure to a boar, with leaving the gilts in their groups for five to 15 days after puberty or five to 15 days after second oestrus. All the groups exposed to boars reached puberty significantly earlier than controls (P less than 0.05) but there was no difference between these groups in their mean age at puberty. However, the synchrony of puberty was significantly greater among the gilts which remained in their groups after puberty (P less than 0.01) or second oestrus (P less than 0.001) than among the gilts which were removed at puberty. Experiment 2 investigated the influence of housing pre-pubertal gilts with penmates induced into puberty with injections of oestradiol benzoate. Puberty was significantly advanced by the presence of penmates regularly exhibiting oestrous periods. Experiment 3 compared the effect of daily exposure to an anoestrous ovariectomised sow, an oestrous ovariectomised sow or a boar, on the attainment of puberty by gilts. Gilts exposed to either an oestrous sow or a boar were significantly younger at puberty than isolated control animals (P less than 0.05) whereas the mean age at puberty of gilts exposed to an anoestrous sow was not significantly different from that of controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595158 TI - Prevalence of benzimidazole-resistance in equine cyathostome populations in south east England. AB - In order to study the prevalence of benzimidazole-resistance in equine cyathostomes, 30 stables in south east England were selected according to strict criteria but with minimum bias to provide three matched groups of 100 horses. One group was treated with fenbendazole, one with pyrantel embonate and the third was left untreated. The overall efficacies of fenbendazole and pyrantel embonate, as judged by the faecal egg-count reduction test, were 56.3 and 95.8 per cent, respectively. The numbers of horses at individual stables were too small to draw conclusions at each stable, but whereas efficacies greater than 85 per cent were recorded for pyrantel at 26 of 27 stables, the corresponding figure for fenbendazole was five of 27. Cyathostomes accounted for more than 90 per cent of the larvae cultured from faeces before and after treatment. Trichostrongylus axei was detected on 20 sites, but Strongylus species were present on only five. In the area of the survey, benzimidazole-resistance was very widespread in stables which used benzimidazole anthelmintics regularly and had more than nine horses per stable, but the benzimidazole-resistant cyathostome strains were adequately controlled with the non-benzimidazole anthelmintic pyrantel embonate. PMID- 1595160 TI - Suspected Lyme borreliosis in sheep. AB - Two cases of suspected Lyme borreliosis in lambs are described. The clinical signs observed resemble those described for Lyme borreliosis in dogs and horses. The lambs were approximately six months old and came from two different flocks in a district heavily infested with Ixodes ricinus ticks. The lambs had pronounced lameness in one leg, generally bad condition and poor appetite. They had high serum levels of IgG antibodies to Borrelia burgdorferi when tested in an ELISA. The other lambs in the flocks were negative to B burgdorferi antibodies. Attempts were made to isolate spirochaetes from one of the lambs, but were unsuccessful. PMID- 1595162 TI - Real-time ultrasound for pregnancy diagnosis in the harbour seal (Phoca vitulina concolor). PMID- 1595161 TI - Survival rate and carcase downgrading after the stunning of broilers with carbon dioxide-argon mixtures. AB - As chickens may rapidly regain consciousness after gas stunning, the effects of a two minute exposure to a carbon dioxide-argon mixture on survival rate were investigated. Broilers were stunned in batches of 10 per transport crate with a mixture of 10, 20 or 30 per cent carbon dioxide in argon with 5 per cent residual oxygen. The birds were exposed to the gaseous atmosphere for two minutes. A control group of birds was electrically stunned (120 mA for four seconds; 50Hz sinusoidal waveform). In addition, the incidence of carcase downgrading conditions after stunning with 20 per cent or 30 per cent carbon dioxide in argon with 5 per cent residual oxygen was compared with the incidence after electrical stunning. The results showed that stunning with 10 and 20 per cent carbon dioxide in argon with 5 per cent residual oxygen resulted in survival rates of 24 and 1 per cent, respectively. Stunning with 30 per cent carbon dioxide in argon with 5 per cent residual oxygen resulted in the death of all the broilers. Electrical stunning resulted in a significantly (P less than 0.001) larger number of broilers with breast muscle haemorrhaging and broken furculum and coracoid bones, whereas stunning with gas mixtures resulted in a significantly (P less than 0.001) higher incidence of broilers with damaged wing bones. Electrical stunning of broilers resulted in a significantly higher pH in the breast muscles 20 minutes post mortem than stunning with carbon dioxide-argon mixtures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595163 TI - An outbreak caused by Mycoplasma mycoides species in goats in the Canary Islands. PMID- 1595164 TI - Serological characterisation of Pasteurella multocida strains isolated from wild ruminants as capsular serogroup B. PMID- 1595165 TI - Tendering for veterinary service contracts. AB - Despite the misgivings of many members of the veterinary profession, tendering for meat hygiene and other veterinary service contracts is becoming increasingly commonplace. In the article below, Mr Martin Cooke, a member of the BVA Company Services Advisory Committee and a veterinarian with extensive experience of public sector work, gives some advice on preparing and submitting a competitive tender. PMID- 1595166 TI - Availability of medicines. PMID- 1595167 TI - Availability of medicines. PMID- 1595168 TI - Embryo transfer legislation. PMID- 1595169 TI - Embryo transfer legislation. PMID- 1595171 TI - Erosion of veterinary influence. PMID- 1595170 TI - Unusual poisoning in a dog. PMID- 1595172 TI - Foreign bodies in dogs. PMID- 1595173 TI - Rabies requirements. PMID- 1595174 TI - Ruminal lactic acidosis in sheep and goats. AB - The clinical findings in 37 sheep and goats with acute ruminal lactic acidosis included a disturbed general condition characterised by anorexia, apathy, teeth grinding and muscle twitching, ruminal stasis, and the excretion of soupy or watery faeces. The ruminal fluid of affected animals was milky, had a sour odour and a low pH. There was a predominance of Gram-positive bacteria in smears of ruminal fluid. In comparison with 10 control animals, the rumen fluid of 23 sheep with ruminal lactic acidosis had higher lactic acid and lower volatile fatty acid concentrations. In addition, the affected animals often had haemoconcentration and metabolic acidosis. Treatment included single or repeated transfer of ruminal fluid from healthy cows and, depending on the severity, the administration of antacids, yeast and chlortetracycline, and the intravenous infusion of isotonic sodium chloride and 5 per cent sodium bicarbonate solutions. Of the 37 treated sheep and goats, four died within 24 hours, and three others were euthanased after one, two and three days because their condition rapidly deteriorated. Thirty animals were discharged one to nine days after treatment. Twenty-nine of them (78.4 per cent) recovered completely but one was euthanased later. PMID- 1595175 TI - Rationale for treatment of retained placenta in cows with neomycin and metronidazole. AB - A combination of neomycin and metronidazole was compared with oxytetracycline for its activity against the intrauterine flora of 10 cows with retained placenta. In vitro the metronidazole/neomycin combination reduced the numbers of aerobic and obligately anaerobic bacteria much more effectively than did oxytetracycline. PMID- 1595176 TI - Field evaluation of an albendazole intraruminal capsule against benzimidazole resistant Haemonchus contortus. PMID- 1595178 TI - Pulse oximetry: everyday uses in a zoological practice. PMID- 1595177 TI - Erosion of incisors in cattle on self-fed silage with enzyme additive. PMID- 1595179 TI - Eosinophilic myositis in a goat. PMID- 1595181 TI - Varroa jacobsoni found in the UK. PMID- 1595180 TI - Tendering for veterinary service contracts. PMID- 1595182 TI - Infection of a marmoset with the BSE agent. PMID- 1595183 TI - 'Frog in the throat'. PMID- 1595184 TI - Animal transport petition. PMID- 1595185 TI - Immunohistology of Peyer's patches in the dog. AB - Canine Peyer's patches were examined by light microscopy and immunohistochemistry for possible variations depending on the location within the small intestine and for similarities and dissimilarities to PPs from other species. The duodenal and jejunal PPs were characterized by relatively large domes and interfollicular areas. In contrast, the ileal PP had small domes and poorly developed interfollicular areas and very large follicles. T cells were found in the interfollicular area and corona and in lesser numbers in the dome and germinal centers. The ileal PP contained far fewer T cells than the proximal PPs. Domes of canine PPs contained some cytoplasmic IgA+ (cIgA+) and many cIgG+ cells. Peanut agglutinin (PNA) stained germinal center cells in a selective but not-uniform way and did not stain T cells. PMID- 1595186 TI - Induction of heat-shock proteins and phagocytic function of chicken macrophage following in vitro heat exposure. AB - The protein profiles and phagocytic ability of Sephadex-elicited chicken peritoneal macrophages were examined following heat-shock exposure. Macrophage cultures were exposed to various temperatures, time exposures and recovery periods. Densitometric analysis of SDS-PAGE autoradiographs revealed that heat induced macrophages synthesized three major (23, 70 and 90 kD) heat-shock proteins (HSPs). The optimal temperature and time for induction of these HSPs was 45-46 degrees C for 1 h, with a variable recovery period for each HSP. Macrophages exposed to 45 degrees C for 30 and 60 min were significantly depressed in phagocytosis of uncoated sheep erythrocytes (SE) under 45 degrees C incubation conditions. However, phagocytosis of antibody-coated SE was not affected when compared to 41 degrees C control cultures. Macrophages allowed to recover at 41 degrees C following heat-shock exhibited no alterations in their phagocytic ability for either antibody-coated or uncoated SE. This study suggests that heat shock induces three major HSPs in chicken peritoneal macrophages in addition to maintaining their Fc-mediated phagocytic function while significantly depressing their nonspecific phagocytosis. PMID- 1595187 TI - Effect of "in vitro" exposure of bovine alveolar macrophages to different strains of bovine respiratory syncytial virus. AB - A vaccine strain of respiratory syncytial (RS) virus and an isolate from pneumonic calves (AC2) were inoculated onto cultures of bovine alveolar macrophages recovered by lung lavage, and the functional properties of the cells observed over a period of 10 days. In most cultures no infectious virus was produced although immunofluorescence indicated the presence of virus antigens in some cells. No significant difference was noted between infected and control macrophage cultures in their capacity to phagocytose latex particles (neutral phagocytosis), although the ability to phagocytose complement-coated Candida krusei cells was affected, particularly with the AC2 strain after 6 days. Killing of C. krusei cells was slightly affected by infection of macrophages with the vaccine strain and was dramatically affected by infection with strain AC2. C3b and Fc receptor expression was adversely affected by both virus strains. Production of neutrophil chemotactic factors was increased in cultures infected with both strains, but was greater with AC2, suggesting that some properties of the cells were activated. PMID- 1595188 TI - Mitogen and antigen-specific induction of lymphoblast transformation in cats with subclinical toxoplasmosis. AB - Lymphoblast transformation in whole blood was assessed by 3H-thymidine incorporation after stimulation by concanavalin A and Toxoplasma gondii secretory and intracellular antigens in samples from cats with experimentally induced toxoplasmosis. Toxoplasma gondii-specific immunoglobulin M, immunoglobulin G, and circulating antigens were also measured throughout the study period. Lymphocytes from all cats were responsive to concanavalin A pre- and post-inoculation with T. gondii. Suppression of mitogen-stimulated lymphoblast transformation during the course of infection was not observed. Both the secretory and intracellular antigens stimulated lymphoblast transformation in many cats from Week 2 to Week 52 post-inoculation. Lymphoblast transformation was stimulated more frequently by intracellular antigens (66.25%) than by secretory antigens (48.75%). Lymphoblast transformation was not induced by T. gondii antigens in any cat prior to appearance of T. gondii-specific antibodies in serum or during the oocyst shedding period. Cats with persistent antigenemia had the most consistent lymphoblast transformation results induced by T. gondii-specific antigens. PMID- 1595189 TI - Biological half-life of ovine antibody in neonatal lambs and adult sheep following passive immunization. AB - Neonatal lambs and adult wethers were passively immunized with ovine antibody directed against ovalbumin or Brucella abortus. Estimates for the biological half lives of the antibodies ranged from 18 to 24 days in neonatal lambs and 12 to 17 days in adult wethers. The evidence suggested that both normal and immunosuppressed wethers which were passively immunized with serum antibody catabolized this antibody at a faster rate than did neonatal lambs. The data provided no support for the hypothesis that the growth factors and immunomodulatory factors, which are known to be present in colostrum, can influence the biological half-life of homologous antibody following passive immunization. PMID- 1595190 TI - Effect of a milk-derived factor on the inflammatory response to Staphylococcus aureus intramammary infection. AB - Daily injections of an anti-inflammatory milk-derived factor (MDF) into mice increased resistance to Staphylococcus aureus challenge, and reduced leukocyte infiltration. Intraperitoneal injection of MDF into lactating mice prior to S. aureus intramammary challenge resulted in greater milk secretory activity and less inflammation compared with untreated controls, but had little effect on the number of S. aureus recovered from mammary tissue. Infusion of MDF directly into mouse mammary glands prior to challenge reduced S. aureus recovered after challenge. Incubation of bovine mammary macrophages in medium supplemented with MDF enhanced phagocytosis of opsonized S. aureus. In addition, infusion of 5 mg MDF into uninfected bovine mammary glands 24 h prior to S. aureus challenge resulted in fewer infections (five of ten) than in control quarters (seven of nine). Repeated daily injections of 5 mg MDF into S. aureus-infected quarters increased the percent of mammary neutrophils and decreased the recovery of S. aureus, but did not eliminate infections. Intravenous injection of 8 g MDF into cows resulted in pronounced leukopenia while the accompanying effect on mammary leukocytes was less marked but followed a similar course. Results suggest that the use of MDF in mice enhanced resistance to experimental infection and was beneficial in maintaining mammary secretory activity and reducing inflammation after bacterial challenge. In the cow, MDF promoted phagocytosis in vitro and was effective against challenge when infused intramammarily. PMID- 1595191 TI - Modification of accessory activity of sheep monocytes in vitro by a coenurus antigen from Taenia multiceps. AB - A factor in Taenia multiceps coenurus fluid (TMCF) has previously been shown to modify the accessory activity of murine macrophages in vivo and in vitro. The factor (TMCF-F24) has been purified by ion exchange in a fast protein liquid chromatography (FPLC) system. This study was conducted to determine whether TMCF F24 is an antigen in naturally occurring cerebral coenuriasis, and whether it can also modify normal sheep blood monocytes. Specific IgG antibodies to TMCF-F24 were detected, using ELISA, in serum and cerebrospinal fluid of sheep with clinical coenuriasis. Alterations in monocyte accessory activity were detected by an assay which measured the rate of increase in mitogen-induced lymphocyte transformation caused by addition of increasing numbers of the monocytes. Normal monocytes caused a positive increase in lymphocyte transformation. Monocytes incubated with TMCF-F24 caused progressive inhibition of transformation. This factor may therefore modify monocyte-T cell interaction in natural infection. PMID- 1595192 TI - Preparation of B lymphocyte-specific alloantisera by skin implant immunization of cattle. AB - B lymphocyte-specific antisera were prepared by immunizing cattle on either one or two occasions with a subcutaneous implant of allogeneic skin and subsequently absorbing the antisera with platelets. After absorption 15/26 antisera displayed B lymphocyte-specific activity. Titres against B-enriched cells were 8-64 while residual titres against B-depleted cells were 1-8. In comparison, 3-6 immunizations with allogeneic leucocytes produced antisera of similar peak cytotoxic titres against donor PBL, and after platelet absorption 8/15 antisera displayed B lymphocyte-specific activity. Titres against B-enriched cells were 8 64 while residual titres against B-depleted cells were 2-8. The skin implant method was less time-consuming than the leucocyte immunization method. PMID- 1595193 TI - A view of neurospinal dysraphism. PMID- 1595194 TI - Prognostic importance of DNA flow cytometrical, histopathological and immunohistochemical parameters in neuroblastomas. AB - In 42 tumour samples of human neuroblastoma, histological classification by differentiation (Shimada) was significantly correlated with strong positivity for neuron-specific enolase (NSE) and inversely correlated with rosette formation. Most ganglioneuroblastomas were positive for S-100 protein and reacted strongly with NSE antibody. Histological signs of high proliferative activity included intermediate or high mitosis-karyorrhexis index, necrosis and lack of calcification, which were significantly correlated with each other. Flow cytometric DNA analysis demonstrated that 88% of the tumour samples had DNA aneuploid stem lines. High S phase fraction (greater than or equal to 0.20) was significantly correlated with necrosis and lack of calcification. Univariate analysis of prognosis for 26 patients whose tumour samples were obtained before adjuvant treatment showed that five factors were significantly related to a better outcome: early stage of the disease (stages I, II, IV-S), S phase fraction less than 0.20, favourable Shimada histology, positivity for S-100 protein, and strong positivity for NSE. In multivariate analysis, only S phase fraction or stage of disease remained significantly associated with prognosis. DNA index did not correlate with prognosis in this study. PMID- 1595195 TI - Intramembranous fine deposit disease associated with collagen disorders: a new morphological entity? AB - A distinct, hitherto unknown renal histopathological appearance, consisting of diffuse thickening of the glomerular basement membrane (GBM) with fine intramembranous electron-dense deposits, was observed in the renal biopsies from three patients with collagen diseases. In each case, proteinuria was mild with normal urinary sediment. On light microscopy there were no particular abnormalities but a mild thickening of the glomerular capillary wall. Immunofluorescence studies revealed faint linear or extremely fine granular IgG deposition along the capillary wall. On electron microscopy, the GBM was diffusely thickened with fine intramembranous electron-dense deposits without spike formation. No other deposits were seen in the glomerulus. These histological features resembled those of membranous glomerulonephritis (MGN), although the possibility of the early change of MGN is excluded by specific findings in these cases. Other GBM-thickening diseases such as diabetic glomerulosclerosis were ruled out clinically and histologically. Our cases have a singular renal histopathology which differs from any of the previously established classifications of glomerular lesions. It may be a specific change associated with some type of collagen disease. PMID- 1595196 TI - Malignant paraganglioma of the uterus. AB - We report a malignant uterine paraganglioma in a 40-year-old female, who died 7 months after the initial diagnosis. On light microscopy the tumour showed a typical zellballen pattern as well as a pronounced cellular pleomorphism. In many tumour cells hyaline globules were demonstrated within the cytoplasm. Immunohistochemically the lesion was characterized by the presence of neuron specific enolase, protein gene product 9.5 and synaptophysin, and electron microscopically by the occurrence of neurosecretory granules. PMID- 1595197 TI - [Relative contribution of standard and physiologic stimulation for maximal work capacity in patients with complete atrioventricular block]. AB - The influence of heart rate on the maximal work capacity was investigated in 18 patients (mean age 55 years) with a physiological pacemaker implanted on account of chronic complete atrioventricular block of different aetiology. Twelve patients with a dominating atrial sinus activity had a dual chamber DDD pacemaker and six patients with dominating atrial fibrillation or flutter had a single chamber QTVVIR pacemaker. The exercise test was made on a bicycle ergometer using three stimulation regimes in randomized order and without the patient's knowledge of the programmed mode of pacing: 1. VVI pacing with frequency of 30/min exercise on AV block, 2. VVI pacing with a frequency of 70/min, 3. Uhysiological DDD or QT pacing. Patients with atrioventricular block attained an average heart rate of 54 + 9/min and a work capacity of 81 + 31 W. During VVI pacing a mean frequency of 73 +/- 9/min was achieved (+35%, P less than 0.002) and a work capacity of 100 +/ 45 W (+24%, P less than 0.008). The load during physiological stimulation led to an increased heart rate, i.e. to 140 +/- 15/min (+169%, P less than 0.002) and work capacity to 130 +/- 52 W (+61%, P less than 0.002). The increment of work capacity was thus 2.5 times greater during physiological than during standard ventricular pacing (P less than 0.005), when compared with the work capacity of patients during AV block. A more extensive investigation is needed to identify patients who will benefit maximally from physiological pacing. PMID- 1595198 TI - [Late ventricular potentials in patients without ventricular tachycardia 3 years after myocardial infarct]. AB - In 57 patients who in the course of 29-48 months (mean 36 months) after myocardial infarction did not develop sustained ventricular tachycardia, late ventricular potentials were investigated. Positive findings were revealed in 13 (22.8%) patients using a 25-250 Hz filter and in 14 patients resp. (24.6%) using a 40-250 Hz filter. Late ventricular potentials were significantly more frequent in patients after myocardial infarction of the lower rather than the anterior wall (p less than 0.05). No differences were revealed between groups with positive and negative late ventricular potentials as regards the occurrence of repeated infarction, left-side cardiac failure, ectopic ventricular contractions, diabetes mellitus, arterial hypertension and cardiothoracic index. The assembled data are comparable with data in the literature pertaining to the incidence of late ventricular potentials in patients after myocardial infarction without sustained ventricular tachycardia. PMID- 1595199 TI - [Endarterectomy of the coronary arteries]. AB - The authors analyze 50 patients with endarterectomy of the coronary arteries during the periods of 1972-1974 and 1988-1990. The results of endarterectomy of the right and left coronary artery provide evidence of its justification in indicated cases whereby contrary to some departments the results of endarterectomy of the left coronary artery are comparable with endarterectomy of the right coronary artery. PMID- 1595200 TI - [Midazolam during cardiac pacemaker implantation]. AB - Midazolam (Dormicum Roche) was administered to 40 patients aged 68 +/- 11 years (5 mg by the i.v. route), along with phentanyl and droperidol before primo implantation or replacement of pacemaker under local anaesthesia. Another 5 mg were administered at the end of the operation before the final skin suture. In all patients a favourable sedative effect was achieved with rapid regression after the operation was completed, in the majority with retrograde amnesia. None of the patients developed respiratory arrest or mental alteration during the postoperative period, while in an equal number of patients in the control group both complications occurred three times. PMID- 1595201 TI - [Enalapril in the treatment of nephrogenic hypertension]. AB - In a half-year open clinical study the authors investigated the antihypertensive action of enalapril--an inhibitor of the angiotensin converting enzyme--and its action on renal functions in a group of 11 patients with nephrogenic hypertension. In seven patients monotherapy, using a mean dose of 12 mg, was sufficiently effective. In the remaining four patients treatment was combined with diuretics. It was revealed: that: 1. a significant drop of systolic and diastolic pressure occurred with a concurrent decline of the total peripheral vascular resistance, 2. a slight (statistically not significant) reduction of the glomerular filtration as well as quantitative proteinuria with a decline of glomerular hypertension. 3. In this group of patients without left ventricular hypertrophy no signs of regression of its mass were present. 4. Even in patients with nephrogenic disease no negative effect on the lipid, carbohydrate and purine metabolism was observed. The subjective tolerance of the preparation was very satisfactory. PMID- 1595202 TI - [Response to a series of carbon dioxide baths]. AB - The authors investigated 28 patients, mean age 43.6 years, during their stay in spa Dudince. The patients had a daily carbon dioxide bath, thermally indifferent, for a period of 20 minutes. During the first, tenth and twentieth bath the humoral circulatory and renal response was assessed. During every bath a standard reaction developed (decline of plasma renin activity and of the aldosterone level, increased excretion of water and minerals, changes of the blood pressure and heart rate). The influence of the series of baths was manifested by a gradual increase of the diuresis, natriuresis, a more permanent drop of the blood pressure and at the end of the series also of the heart rate. The other investigated parameters did not change significantly during the series of baths, as compared with the reaction to a single bath. The attained results justify the conclusion that a series of carbon dioxide baths had a gradually improving effect which is favourable, in particular in the treatment of cardiovascular diseases. PMID- 1595203 TI - [Feldene in local therapy of deforming gonarthroses]. AB - The author submits the results of Feldene gel therapy which contains 5 mg piroxicam per 1 g. The preparation was applied to patients with deforming gonarthrosis, always on one joint three times per day for two weeks. The evaluation was made before the unset of treatment and on the 7th and 14th day. It was an open clinical therapeutic trial. In 97.5% the tolerance was excellent. Undesirable manifestations developed only in one female patients who had sensations of irritation which disappeared in three days and interruption of treatment was not necessary. The authors evaluated pain, mobility, required assistance during change of position-sitting and standing up and when climbing stairs. The evaluation was made by the physician and the patient. Significant results were achieved in particular as regards pain but also in the other parameters. In more than 90% regression of all evaluated criteria was recorded. The preparation is evaluated very favourably. It helps not only in treatment proper but has also a comprehensive effect. Feldene gel is an important asset to local treatment in rheumatology and will be most probably valuable also in orthopaedics, surgery and sports medicine. PMID- 1595204 TI - [Prognostication of chronic Ph+ myeloid leukemia using the PHCML.EXE computer program]. AB - In 193 patients with Ph-positive chronic myeloid leukaemia (CML) Sokal's calculation formulae prognosticating initial risk status were applied, using the computer program PHCML. The aim of this study was to the prognostic reproducibility of these prognostic staging systems in our patient population. Our results confirm the previous conclusions that prognostic discrimination is possible at the time of diagnosis of CML but in our patients with poorer prognosis the stratification seems to be more accurate. No significant advantage was achieved when we prognosticated our patients younger than 46 years using the formula recommended by Sokal et al. specifically for younger patients. We analyzed different criteria when segregating patients in groups with better or poorer prognosis. We found that the coefficient of the patient's relative risk as the boundary, was 1.9 our patient's group contrary to 1.2 in Sokal's studies. PMID- 1595206 TI - [Detection of HLA-DR antigens using the ethidium bromide fluorescence test]. AB - HLA-DR antigens were examined in peripheral lymphocytes by means of a one-colour fluorescent microcytotoxic test using ethidium-bromide. Evidence of HLA-DR antigens was equally reliable as the two-colour fluorescent test. Contrary to the latter, however, faint non-specific positive results were obtained in sera not containing HLA-DR antibodies. This is caused probably by the fact that ethidium bromide penetrates into cells with a very slightly damaged membrane. This reduces substantially the possibility of introduction of the method into common practice. PMID- 1595205 TI - [Comparison of Tarivid and Biseptol in the prevention of bacterial infections in patients with acute leukemia]. AB - In 42 patients with induction treatment of acute myeloblastic and lymphoblastic leukaemia the authors compared efficacy of selective decontamination of the gastrointestinal tract in prevention of infections during neutropenia less than 0.5.10(9)/l in two comparable groups. Twenty-two patients were treated with Ofloxacin (Tarivid, Hoechst Co.), 20 patients with Trimetroprim-Sulfamethoxazol (Biseptol, Polfa Co.). Both groups had concurrently also Ketoconazol in prevention of mycotic infection. The investigation revealed that Tarivid is a suitable alternative drug for selective decontamination, because it delays the onset of acquired infection, as compared with Biseptol, it reduced more efficiently the frequency of Gram-negative colonization and life-threatening Gram negative sepsis, caused by resistent strains; its tolerance is significantly better. There was no significant difference in the occurrence of febrile days, febrile episodes, the duration of antibiotic treatment, the number of sepsis in two groups. The effect of Tarivid and Biseptol on the Gram-positive microbial flora is inadequate. Subclavian catheter increases in particularly the risk of Gram-positive sepsis in both groups. PMID- 1595207 TI - [Thymoma in the anterior mediastinum and systemic lupus erythematosus]. AB - The authors describe an observation of a thymoma and systemic lupus erythematosus (SLE) in a 48-year-old woman with an analysis of clinical and laboratory indicators justifying this diagnosis. Improvement of SLE and the lupus nephropathy was achieved by three pulses of methyl prednisolone a 1000 mg in an intravenous infusion with subsequent Prednisone therapy, using conventional doses. After thymectomy on account of a benign thymoma activation of SLE did not occur. The objective of the presented paper is to draw attention to the infrequent possible concurrent incidence of thymoma and SLE and the influence of thymectomy and the subsequent development of SLE. PMID- 1595208 TI - [Characteristics of diabetic macroangiopathy of the lower extremities]. AB - Macroangiopathy of the lower extremities is one of the most frequent complications of diabetes and has a very adverse impact on the quality of life of the patients. It affects approximately as much as half the diabetics with the duration of the disease for more than 15 years. It is encountered in two forms. The first type of affection--obliterating atherosclerosis--reminds of affections of the arteries of the lower extremities in the non-diabetic population, although some differences in the site of affection, morphology of sclerotic changes as well as the spectrum of risk factors were found, when compared with obliterating atherosclerosis in non-diabetics. Risk factors of this form of macroangiopathy include cholesterol, triacylglycerols, reduced values of HDL-cholesterol, hypertension, fibrinogen, smoking and apparently also albuminuria. The second form of macroangiopathy--mediocalcinosis--is not associated with the mentioned risk factors of atherosclerosis but is probably the consequence of diabetic neuropathy. Contrary to atherosclerosis, it does not lead to the development of obliteration but has also an adverse effect on the function of blood vessels. Its incidence correlates with the duration and compensation of diabetes as well as deteriorated perception of vibrations. With regard to the high incidence of gangrenes requiring amputation, it seems rational to influence in diabetics all known risk factors of macroangiopathy although convincing results of long-term intervention studies are still lacking. PMID- 1595209 TI - [Dietary recommendations of the Czech Diabetology Society for adults with diabetes mellitus]. PMID- 1595210 TI - [Can pharmacotherapy in heart failure affect mortality?]. AB - The prognosis of patients with advanced chronic cardiac failure is very poor. Only investigations made in recent years provided evidence that this adverse prognosis can be influenced by conservative pharmacological treatment. Among many tested vasodilating substances positive data were obtained only with high doses of nitrates with hydralazine and in particular with inhibitors of the angiotensin converting enzyme which are the greatest advance in the treatment of chronic cardiac failure. Preparations of this group mitigate the symptomatology, increase load tolerance and improve the prognosis. So far they are indicated above all in severe forms of cardiac failure, however, the possibility to use them also in milder forms and in patients with myocardial infarction is intensively investigated. The basis of pharmacological treatment remain diuretics. The position of digitalis in the treatment of cardiac failure is revised at present; in a major proportion of patients, in particular those with a preserved sinus rhythm, its administration is useless. A number of other positively inotropic substances was tested, catecholamines as well as phosphodiesterase inhibitors (amrinone, milrinone, xamoterol, enoximone). Contrary to acute failure, their effect in chronic failure is controversial, data on an improved prognosis are lacking and some investigations reveal an adverse trend. Almost half the patients with cardiac failure die from a sudden death and it would thus be logical to use antiarrhythmic drugs. Here, too, however, data on an improved diagnosis are lacking. The results of hitherto accomplished studies were rather disappointing, the investigation with the most promising antiarrhythmic agent--amiodarone--is still under way. PMID- 1595212 TI - [Echocardiographic evaluation of the left ventricle in mild hypertension treated with physical exercise]. AB - The authors submit findings of haemodynamic changes during long-term treatment of mild hypertension by physical training. Using this method, blood pressure was normalized in all subjects. The authors conclude that physical activity has a similar impact on the haemodynamics of mild hypertension as drugs which reduce the tension of the sympathetic nerve. A surprising finding was the diminution or complete disappearance of cardiac hypertrophy in this treatment. PMID- 1595213 TI - [Permanent variable frequency cardiac pacing: which patients with chronic complete atrioventricular block profit most?]. AB - The authors examined 27 patients with chronic complete atrioventricular block (AVIII) and an implanted pacemaker with rate responsive pacing (RRP), controlled by atrial frequency (DDD stimulation--19 patients) or the length of the QT interval (VVIR pacing--8 patients). The loading test in AVIII ventricular stimulation 70/min (VVI 70) and RRP proved a more than double asset of MKP in RRP, as compared with VVI 70 (55.5 +/- 43.3% vs. 24.3 +/- 34.1%, p less than 0.001). The difference was greater in acquired than in congenital AVIII (27.7 +/- 18.5% vs. 8.4 +/- 4.1%, p less than 0.002) and in patients where the maximum heart rate on VVI did not exceed 70/min, as compared with the remainder (29.3 +/- 19.1% vs. 12.7 +/- 8.1%, p less than 0.002). The difference of MPK in RRP and VVI 70 was inversely correlated with MPK on VVI 70 (r = -0.412, p less than 0.03). MPK on AVIII and MTF on VVI 70 (r = -0.386, p less than 0.05). RRP in patients with AVIII thus causes a double increase of MPK, as compared with VVI pacing. A greater asset can be expected in patients with acquired AVIII, with a lower working capacity and heart rate recorded during the loading test before implantation. PMID- 1595211 TI - [Computer-assisted electrocardiographic mapping and left ventricular function in patients with acute myocardial infarct]. AB - In 22 patients with a first myocardial infarction the authors assessed the relationship between morphological changes of the QRS complex and systolic left ventricular function. Using a 56-lead computer-assisted electrocardiogram from the precordium in the form of a map (apparatus Cardiomap-1), the authors prepared a record during the first days after initiating treatment with a thrombolytic agent and again after a period of three weeks. They found only one correlation between the decrement of Q waves and the increase of the left ventricular ejection fraction (p less than 0.05). This correlation, however, is of no practical importance due to the low correlation coefficient. The relationship is moreover markedly influenced by the time of the first record. After the third day of thrombolytic treatment it is not expedient to make the initial record. No relationship between the change of R waves, ST segments and left ventricular function was found. Similarly, due to the great dispersal of values it is not possible to differentiate between patients with inferior infarctions of the heart muscle and anterior myocardial infarctions. PMID- 1595214 TI - [Esophageal stimulation in WPW syndrome]. AB - Transoesophageal stimulation of the atria combined with bicycle ergometry provides a satisfactory reproducibility of a number of basic electrophysiological parameters at rest and during a load. Due to the good sensitivity and low specificity this test can be recommended in WPW syndrome as a screening examination in particular in active sportsmen and junior subjects. To assess the risk of sudden death in subjects with this syndrome it is, however, necessary to evaluate the complex of all assembled data, as the shortest R-R interval in induced atrial fibrillation is not sufficiently specific. PMID- 1595215 TI - [Serial testing of antiarrhythmic agents using programmed stimulation in recurrent ventricular tachycardia]. AB - Serial testing of drugs (STL) by means of programmed electric stimulation (PES) was implemented in 41 patients with relapsing monomorphic persisting ventricular tachycardia (S-KT) of varying aetiology and severity. To reduce underrating of the action of antiarrhythmics, milder criteria were used for evaluation of the short-term and long-term effectiveness of therapy. By STL a total of 137 drugs and their combinations were tested. S-KT was not induced by 60 of them (44%) and in 35 patients (85%). In the remaining 6 patients STL could not be completed because of non-adherence of the patients to the method or because of serious proarrhythmic action of therapy. In the course of long-term follow up (mean 21 months) in positive therapy an arrhythmic episode did not occur during the first year in any of the patients, in the course of two years it occurred in 14%, in three years in 29% and in the course of four years in 33% of the patients. Treatment preventing S-KT had to be abandoned because of serious side-effects in four patients. In all of these four patients later an arrhythmic episode developed. Long-term treatment with antiarrhythmics selected by means of STL by programmed stimulation is a rational approach to pharmacotherapy of serious ventricular arrhythmias. In cases leading to combined treatment with amiodarone and antiarrhythmics class I it would be, however, better in view of the high incidence of serious effects of this treatment to use implantation of a defibrillator. PMID- 1595216 TI - [Ebstein's anomaly (a group of 47 patients)]. AB - In a group of 47 patients with Ebstein's anomaly followed up on a long-term basis the authors describe the natural course of the disease as well as contemporary diagnostic and therapeutic possibilities. The authors draw attention to typical symptoms of Ebstein's anomaly and emphasize the importance of early diagnosis by two-dimensional echocardiographic and Doppler examination and the introduction of individual conservative or surgical treatment. PMID- 1595217 TI - [ECG Holter monitoring in patients with chronic renal failure in a long-term dialysis program]. AB - Using the Holter method, the authors monitored for 24-hours 30 patients included in a long-term dialyzation programme during and after haemodialysis. A group of 15 patients who had during examination frequent or complex supraventricular or ventricular ectopia was compared with a group of 15 patients with sporadic ectopia. In the arrhythmic group paroxysmal supraventricular tachycardia was recorded in 33% and paroxysmal atrial fibrillation in 13%, polytopic or repetitive ventricular extrasystoles in 14%, couplets in 20% and volleys of ventricular extrasystoles or non-persisting ventricular tachycardia in 20%. Comparison of clinical laboratory and echocardiographic characteristics revealed in the arrhythmic group significantly higher mean ages of patients, higher levels of ionized serum calcium before haemodialysis, C terminal parathormone, the breadth of the interventricular septum, and the authors observed also a higher incidence of hyperechogenity of cardiac structures. On analysis of repolarization ECG changes significant asymptomatic depressions of the ST segment were found which were transient and dominated during the early posthaemodialyzation period in 11 patients of the whole group (37%). PMID- 1595218 TI - [Complete recovery of left ventricular function after myocardial infarct]. AB - In a 27-year-old patient with an infarction of the anterior myocardial wall, significant from the haemodynamic aspect, a complex procedure is described by which in the course of four hours after the beginning of complaints normalization of the lumen and blood flow of the coronary artery supplying the infarction focus was achieved. The authors used thrombolytic intravenous treatment which involved infusion of 1.5 million u. of streptokinase (Streptase, Boehringer, Ingelheim) in the course of 45 mins., N-acetylcysteine 2.0 g i.v. (Broncholysin, Spofa) and percutaneous transluminal coronary angioplasty. In the course of 16 days the left ventricular function recovered completely: the ejection fraction was 67% before the infarction, on the first day of infarction 45% and before discharge 64%. PMID- 1595219 TI - [Cardiac pacing therapy of late intermittent AV block after surgery for tetralogy of Fallot]. AB - Postoperative atrioventricular block may be the cause of early or late death unless diagnosed and treated in time. The authors describe the development of late intermittent complete intraventricular block in an 11-year-old girl with syncope nine years after radical correction of the tetralogy of Fallot. Incomplete trifascicular block was diagnosed by electrophysiological examination of the conduction system four years before the development of complete trifascicular block. With regard to the serious character of an intermittent block cardiac pacing therapy was used. PMID- 1595220 TI - [Wilson's disease and pregnancy]. AB - The authors describe the case of a 27-year-old female patient with Wilson's disease who during penicillinamine treatment became pregnant and was delivered of a healthy infant. The diagnosis of Wilson's disease was confirmed by the finding of a Kayser-Fleischer ring in the cornea and a concurrent serum ceruloplasmin concentration lower than 0.20 g/l. Unrecognized and untreated, the disease is associated with the development of organ complications which in the end prove fatal. On the other hand, early diagnosis and effective treatment throughout life can prevent liver and brain damage and thus enable the patient to live a normal life and women can have a healthy child. PMID- 1595221 TI - [Manifestations and early course of type I diabetes mellitus--a decisive period from the viewpoint of controlling the further development of the disease]. AB - The autoimmune process focused on B-cells of the islets of Langerhans and leading gradually to their destruction is latent before the manifestation of diabetic symptoms. The detection of this preclinical stage in particular in sporadic cases is in common clinical practice, due to the low prevalence of the disease in the population and pretentious character as regards applied methods, unreal. Therefore attention is focused on the period of clinical manifestation of the diabetic syndrome and its early stages when by early diagnosis and intensive insulin or immunosuppressive treatment it is still possible to preserve a substantial proportion of functional B-cells and influence in an effective manner the onset and duration of remission. The authors summarize experience assembled during the eighties, incl. therapeutic procedures and problems of active immunomodulation in the prehyperglycaemic stage of the disease. PMID- 1595222 TI - [Primary hyperaldosteronism, problems in diagnosis and therapy in clinical practice]. AB - The paper summarizes data from the recent literature on pathogenetic variants of primary hyperaldosteronism, screening, diagnosis and therapy of this secondary form of arterial hypertension. On examples from their own practice the authors draw attention to the that the diagnosis and treatment of this disease is not always as straightforward as might appear from the literature. The solution is simple, effective screening in every hypertensive patient by examination of the kalaemia before treatment of arterial hypertension is started. In case of hypokalaemia the subsequent procedure should be the concern of specialized departments. PMID- 1595223 TI - [Lambliasis or giardiasis?]. PMID- 1595224 TI - [Methods and results of Nd YAG laser capsulotomy in pseudophakia]. AB - Methods and results in the use of Nd-YAG laser in capsulotomy (membranoectomy) of secondary cataracts in pseudophakia are presented. The specificity of this procedure is the closeness of the implanted artificial lens to the site of laser effects. PMID- 1595225 TI - [Psychological structure of personality and motivation in blood donors]. AB - The study comprised 500 persons who donated blood for five and more times. The psychic personality structure was studied by EMOTIONS PROFILE INDEX tests with the forced-choice personality index (4) by Henry Kellerman and Robert Plutchnik. Blood donor motivation was examined by the standardized questionnaires which was interpreted by the so-called keys of desirable responses, separately for every potentially primary motive (altruism; habits; superiority complex; inferiority complex; selfpunishment; benefit; indefinite motive). The aim of the study was to assess whether the psychic structure of a personality has effects on blood donor motivation. The study has shown that: a) the psychic personality structure in repeated blood donors has effects on their blood donor motivation; b) altruism is the most common motive for blood donation in persons with the emotionally stable structures of personality and in persons with neurotic potentials; c) among persons with different psychic personality structure there are differences in the percentage of some of primary motives for blood donation. The altruism is the most common motive for blood donation found in 85% of repeated blood donors. All other motives together are found in 8% of cases while in 7% of the examines it was not possible to confirm the primary motive for blood donation. PMID- 1595226 TI - [Evaluation of the association of cancer of the esophagus, stomach and colon with habits of patients]. AB - The demographic characteristics (sex, age, occupation) of patients with cancers of the esophagus, stomach and colon are reported and the importance of smoking and consumption of alcohol and coffee in development of the disease have been evaluated. The etiologic studies comprised 366 patients (100 with esophageal cancer, 80 with stomach cancer and 186 with colon cancer) and 366 controls. NcNamary test was used in differentiation of the rates of the matched samples. The most significant relationship of smoking and alcohol consumption was found for esophageal cancer (RR = 4.4; RR = 9.0, p 0.0001), somewhat less for stomach cancer (RR = 2.0, p 0.05; RR = 1.5) and least for colon cancer (RR = 0.9, RR = 1.1). Coffee consumption was most frequent in patients with cancer of the esophagus and colon while negative correlation was obtained for stomach cancer. PMID- 1595227 TI - [Neurophysiologic evaluation of cognitive disorders in patients with epilepsy]. AB - Aiming to evaluate cognitive disorders in patients with epilepsy examinations were performed using WB scale and event related potentials (ERP) as well as in the control group of healthy volunteers. The study involved 12 patients with epilepsy aging from 15 to 65 years and duration of the disease from 5 to 21 years, 8 males and 4 females: 9 patients received monotherapy and 3 polytherapy. Auditory ERP were studied by averaging 128 expected responses. Recording electrodes were placed by the 10-20 system at sites Fz, C3, Cz, C4, Pz, P4. After recording of the repeated responses the determination of latency of P-300 wave and N2-P3 amplitude were performed. Prolongation of latency of P-300 wave and increased amplitude were recorded in patients with polytherapy and longer duration of the disease. It has been concluded that in patients with chronic epilepsy treated by polytrauma there are changes of the basic characteristics of the parameters of of the cognitive evoked responses. PMID- 1595228 TI - [Controlled trial of short-term chemotherapy in pulmonary tuberculosis, final study]. AB - 178 new cases of tuberculosis of the lungs and pleura have been treated within the period of four years (1985-1988) in military medical institutions of the Y.P.A. The patients were classified by random selection in two therapeutical groups. Two six-month regimens were applied with the same drugs except for the fourth one which was used in the initial period only (EHRZ and SHRZ). Both applied therapeutical combinations were equally successful. All patients achieved negative cultures at least three months after onset of chemotherapy. Relapses occurred in 4 (2.3%) of patients during the period of follow-up for at least 2 and the most 5.5 years after the end of therapy. The toxic effects were tolerable. The drug resistance was found in 25 of 134 (18.6%) patients, the most common to one drug. PMID- 1595230 TI - [Prevention of tetanus in members of the armed forces]. PMID- 1595229 TI - [Enanthema fixum as side effect in the use of a combination of trimethoprim and sulfamethoxazole]. AB - Cases of fixed drug eruption due to trimethoprim-sulfamethoxazole combination are reported. In these cases the oral mucous membranes were affected. Fixed drug eruption is a distinct entity characterized by the development of circular erythematous lesions which over a period of time becomes violaceous. Sulfamethoxazole is probably the main cause of this drug eruption but there are some reports that trimethoprim itself can cause them too. PMID- 1595231 TI - [Autologous transfusion--strategies and indications]. PMID- 1595232 TI - [Persistent carotid-basilar anastomosis]. PMID- 1595233 TI - [Immunoprophylaxis--achievements, perspectives and problems]. PMID- 1595234 TI - [Ossified chronic epidural hematoma]. PMID- 1595235 TI - [Ectopic thyroid tissue in the myocardium of the right ventricle]. PMID- 1595236 TI - [Mucocele of the sphenoid sinus as a diagnostic problem]. PMID- 1595237 TI - [Ixodes ricinus proven as a vector of Lyme borreliosis in Yugoslavia]. AB - 263 fasting female Ixodes ricinus were examined for Borrelia burgorferi, the vector of Lyme borreliosis. Female ticks were collected by flagella in the biotopes (Belgrade and Osijek) in which ticks bite patients with Lyme borreliosis. Borrelia burgorferi was proved in 58 (22%) of 263 female ticks in the native preparations of the intestinal contents by darkfield microscopy. In macerates of two groups of 5 female ticks each, Borrelia burgorferi was isolated by cultivation in the modified Kelly nutrient media for borrelia. The supposition that Ixodes ricinus is the vector of Lyme borreliosis in Yugoslavia is confirmed. PMID- 1595239 TI - WSNA PAC ahead of its time. PMID- 1595238 TI - Our third house. Nursing, politics and you. PMID- 1595240 TI - Ask the nurse attorney. Delegation of duties. PMID- 1595241 TI - Making research work for you. PMID- 1595242 TI - Disposable products in the hospital waste stream. AB - Use of disposable products in hospitals continues to increase despite limited landfill space and dwindling natural resources. We analyzed the use and disposal patterns of disposable hospital products to identify means of reducing noninfectious, nonhazardous hospital waste. In a 385-bed private teaching hospital, the 20 disposable products of which the greatest amounts (by weight) were purchased, were identified, and total hospital waste was tabulated. Samples of trash from three areas were sorted and weighed, and potential waste reductions from recycling and substituting reusable items were calculated. Business paper, trash liners, diapers, custom surgical packs, paper gowns, plastic suction bottles, and egg-crate pads were among the 20 top items and were analyzed individually. Data from sorted trash documented potential waste reductions through recycling and substitution of 78, 41, and 18 tonnes per year (1 tonne = 1,000 kg = 1.1 tons) from administration, the operating room, and adult wards, respectively (total hospital waste was 939 tonnes per year). We offer specific measures to substantially reduce nonhazardous hospital waste through substitution, minimization, and recycling of select disposable products. PMID- 1595243 TI - Management of alcoholism in the primary care setting. AB - Primary care physicians can play an important role in managing alcoholic patients. Identifying and treating alcoholism early, before it has interfered with patients' relationships and work, may increase the likelihood of prolonged recovery. Simple office interventions can help motivate patients to abstain and seek treatment. People who abuse alcohol and are unwilling to abstain can benefit from a recommendation to reduce their intake of alcohol. For alcohol-dependent patients who decide to stop drinking, primary care physicians often can manage withdrawal on an outpatient basis. Selecting an appropriate treatment program for each alcoholic patient is important, and referral to a specialist to assist in matching patients to treatments is often necessary. Primary care physicians also can help prevent relapse. Although disulfiram is of limited value, primary care physicians can support recovery by identifying coexistent psychosocial problems, helping patients to restructure their lives, and ensuring continuity of care. PMID- 1595244 TI - Effects of a major earthquake on calls to regional poison control centers. AB - We retrospectively evaluated the effect of the Loma Prieta earthquake on calls to 2 designated regional poison control centers (San Francisco and Santa Clara) in the area. In the immediate 12 hours after the earthquake, there was an initial drop (31%) in call volume, related to telephone system overload and other technical problems. Calls from Bay Area counties outside of San Francisco and Santa Clara decreased more dramatically than those from within the host counties where the poison control centers are located. In the next 2 days, each poison control center then handled a 27% increase in call volume. Requests for information regarding safety of water supplies and other environmental concerns were significantly increased. The number of cases of actual poisoning exposure decreased, particularly poison and drug ingestions in children. Most calls directly related to the earthquake included spills and leaks of hazardous materials and questions about water and food safety. Regional poison control centers play an essential role in the emergency medical response to major disasters and are critically dependent on an operational telephone system. PMID- 1595245 TI - Blood-brain barrier and new approaches to brain drug delivery. AB - Morbidity caused by brain dysfunction affects more than 50 million persons in the United States. Although new neuropharmaceuticals have the potential for treating specific brain diseases, they may not effectively enter brain from blood. Safe strategies are needed for drug delivery through the brain capillary wall, which makes up the blood-brain barrier in vivo. Two of these strategies are reviewed, as are related new developments in the molecular and cell biology of the brain capillary endothelium. The production of chimeric peptides represents a physiologic-based strategy for drug delivery. It entails the covalent coupling of the neuropharmaceutical to a brain transport vector, allowing transportation through the blood-brain barrier. Another strategy is biochemical opening of the blood-brain barrier: intracarotid leukotriene infusion is a method for selectively increasing blood-brain barrier permeability in brain tumors without affecting barrier permeability in normal brain tissue. PMID- 1595247 TI - Magnetic resonance imaging of musculoskeletal tumors. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in radiology. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in radiology that have recently achieved a substantial degree of authoritative acceptance. Whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Radiology of the California Medical Association, and the summaries were prepared under its direction. PMID- 1595248 TI - Vena cava filters. PMID- 1595246 TI - Clinical significance in alcoholic patients of commonly encountered laboratory test results. AB - An improved understanding of medical problems of alcoholic patients can be gained from commonly encountered laboratory test results. Liver function tests--such as measures of alkaline phosphatase, gamma-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase--may provide evidence of altered hepatic activity of different types, such as obstruction and hepatocellular injury. Other test results may indicate impaired hepatic function, such as measurements of albumin, bilirubin, prothrombin time, and blood urea nitrogen. Alterations are also common in electrolytes, blood glucose, magnesium, phosphate, uric acid, and acid-base balance. Disturbances in hematologic function are not infrequent in alcoholic patients, including anemias from many causes, altered granulocyte responses, and thrombocytopenia. PMID- 1595249 TI - Pelvic magnetic resonance imaging. PMID- 1595250 TI - Magnetic resonance angiography in the head and neck. PMID- 1595251 TI - Intraoperative radiotherapy. PMID- 1595253 TI - Picture archiving and communication systems. PMID- 1595252 TI - Infections in emergency medicine--newer imaging strategies. PMID- 1595254 TI - Shoulder magnetic resonance imaging. PMID- 1595255 TI - The imaging of impotence. PMID- 1595256 TI - Current status of discography. PMID- 1595257 TI - Radiosurgery for tumors and arteriovenous malformations of the brain. PMID- 1595258 TI - Chemoembolization in the treatment of hepatic malignancy. PMID- 1595260 TI - The simplicity and safety of radiologically placed gastric tubes. PMID- 1595259 TI - Vasodilator and exercise cardiac perfusion scintigraphy. PMID- 1595261 TI - The sulfone syndrome in a patient receiving dapsone prophylaxis for Pneumocystis carinii pneumonia. PMID- 1595263 TI - The 'no code' tattoo--an ethical dilemma. PMID- 1595262 TI - Odontoid osteomyelitis. An unusual presentation of an uncommon disease. PMID- 1595265 TI - Kindliness is next to godliness. PMID- 1595264 TI - Ruminations of a teaching surgeon. PMID- 1595266 TI - The medical waste stream. PMID- 1595267 TI - Rational approaches to breaching the blood-brain barrier. PMID- 1595269 TI - The 'gag' rule--a freedom of speech issue? PMID- 1595268 TI - Utility of 'liver function tests' in alcoholic patients. PMID- 1595270 TI - What do hospitals do with HIV-infected staff? PMID- 1595271 TI - How important is a name? PMID- 1595272 TI - Phenotype recognition. Clinicians' contributions to molecular genetics. AB - Medullary cystic disease, Alport's syndrome, and autosomal dominant polycystic kidney disease are inherited renal disorders whose genetic bases are better understood because of careful clinical observation. I explore the relationships among some clinical aspects of each of these conditions, the rapidly advancing field of molecular genetics, and the ethical issues that need to be addressed before gene identification becomes too widely applied as a diagnostic tool. PMID- 1595274 TI - Disruptive medical patients. Forensically informed decision making. AB - Patients who disrupt medical care create problems for physicians. The risks are not entirely clinical. Although these patients may compromise sound clinical judgment, some are also litigious and express their dissatisfaction in legal or other forums. It then becomes necessary for treating physicians to be aware of the legal and ethical boundaries of their patient care responsibilities. Some disruptive patients are treated by setting limits, which is usually affirmed by health care agreements. A hospital review board may advise clinicians on these agreements and on the management of disruptive patients. If termination of the physician-patient relationship is considered, physicians must follow proper protocol. We examine these forensic considerations and place them in the context of malpractice. Communication, consultation, and documentation are the key elements in reducing liability. PMID- 1595273 TI - Cancer screening in older adults. AB - Adults aged 65 and older represent an increasingly important segment of the US population. Cancer is an important cause of death in this group. Screening for cancer can significantly reduce cancer incidence and mortality. In this review I address screening for breast, cervical, prostate, lung, colorectal, and ovarian cancer in older Americans. Decisions about screening for cancer must consider the effects of screening, diagnostic evaluations, and treatments on the quality of life of each person. PMID- 1595275 TI - Use of traditional health practices by Southeast Asian refugees in a primary care clinic. AB - To determine the prevalence of use of traditional health practices among different ethnic groups of Southeast Asian refugees after their arrival in the United States, we conducted a convenience sample of 80 Cambodian, Lao, Mien, and ethnic Chinese patients (20 each) attending the University of Washington Refugee Clinic for a new or follow-up visit. Interpreters administered a questionnaire that dealt with demographics, medical complaints, traditional health practices, health beliefs, and attitudes toward Western practitioners. In all, 46 (58%) patients had used one or more traditional health practices, but the prevalence varied by ethnic group. Coining and massage were used by all groups except the Mien, whereas moxibustion and healing ceremonies were performed almost exclusively by the Mien. Traditional health practices were used for a variety of symptoms and, in 78% of reported uses, patients reported alleviation of symptoms. The use of traditional health practices is common among Southeast Asian refugees. Clinicians who care for this population should be aware of these practices because they may supersede treatments prescribed by physicians or leave cutaneous stigmata that may be confused with disease or physical abuse. Good patient care may necessitate the use or tolerance of both Western and traditional modalities in many Southeast Asian refugees. PMID- 1595276 TI - Purchasing prescription medication in Mexico without a prescription. The experience at the border. AB - Prescription medication can often be purchased in Mexico without a physician's prescription. United States residents living along the border may have access to dangerous medications by crossing the border and purchasing them in Mexican pharmacies. We sought to determine the extent and frequency of this behavior in a sample of our ambulatory clinic population. Patients from the Texas Tech University Internal Medicine Clinic were surveyed to collect information about their use of medications, use of alternative sources of health care in Mexico, and purchasing of prescription medication in Juarez, Mexico. More than 80% of patients stated they had purchased prescription-type medication at a pharmacy without a physician's prescription. The most common reasons for buying prescription medication in Mexico were because it was less expensive or because a prescription was not necessary. These data indicate a potential for US residents along the border to take medications in an unregulated manner, a practice that could pose problems for health care providers on both sides of the border. PMID- 1595277 TI - 47-year-old woman with six-week history of lower extremity weakness and eosinophilia. AB - This discussion was selected from the Department of Medicine Morbidity and Mortality Conference held at the Stanford University Medical Center, Stanford, California, on January 9, 1991. The editor of the conference is Philip C. Lee, MD, Chief Resident, Department of Medicine. PMID- 1595279 TI - Using health risk appraisal in clinical practice. AB - The Scientific Board of the California Medical Association presents the following inventory of items of progress in preventive medicine and public health. Each item, in the judgment of a panel of knowledgeable physicians, has recently become reasonably firmly established, both as to scientific fact and important clinical significance. The items are presented in simple epitome, and an authoritative reference, both to the item itself and to the subject as a whole, is generally given for those who may be unfamiliar with a particular item. The purpose is to assist busy practitioners, students, researchers, or scholars to stay abreast of these items of progress in preventive medicine and public health that have recently achieved a substantial degree of authoritative acceptance, whether in their own field of special interest or another. The items of progress listed below were selected by the Advisory Panel to the Section on Preventive Medicine and Public Health of the California Medical Association, and the summaries were prepared under its direction. PMID- 1595280 TI - Lead exposure. PMID- 1595281 TI - Anticipating the arrival of cholera from Latin America. PMID- 1595278 TI - Tumors of the kidney, ureter, and bladder. AB - Neoplastic diseases of the kidneys and urinary collecting system are relatively common, but when detected early, they have an excellent prognosis. Because gross or microscopic hematuria may be an early harbinger of genitourinary pathology, the primary care physician and internist play an integral role in diagnosing these diseases. A high index of suspicion together with a thorough history, physical examination, and appropriate diagnostic studies will enable the correct diagnosis and improved patient management in most cases. PMID- 1595282 TI - Clove cigarettes. PMID- 1595283 TI - Health and electromagnetic fields. PMID- 1595284 TI - Recruitment for the beta-carotene and retinol efficacy trial (CARET) to prevent lung cancer in smokers and asbestos-exposed workers. PMID- 1595285 TI - Sarcoidosis presenting with an unusual erythematous rash and persistent hypercalcemia. AB - Sarcoidosis is a multisystem disease that often presents with constitutional symptoms and ocular and skin manifestations. The chest roentgenogram may show no abnormalities or only diffuse interstitial disease. The serum calcium level is uncommonly persistently elevated and responds rapidly to low-dose corticosteroid therapy. The level of 1,25-dihydroxyvitamin D is often elevated, and the level of parathyroid hormone is almost always suppressed. Skin manifestations vary considerably and may appear in an unusual fashion. A skin biopsy may often be essential in the diagnosis of sarcoidosis. PMID- 1595286 TI - Primary biliary cirrhosis and adult celiac disease. PMID- 1595287 TI - On sale: future health care. The paradox of discounting. PMID- 1595288 TI - First World exports to the Third World--capital, technology, hazardous waste, and working conditions--who wins? PMID- 1595289 TI - Genetic heterogeneity and clinical disease. PMID- 1595290 TI - Health problems in the Chinese in North America. PMID- 1595291 TI - More on the 'gag rule'. PMID- 1595292 TI - Treating status epilepticus. PMID- 1595293 TI - Psychological morale and job satisfaction among homecare workers who care for persons with AIDS. AB - This paper reports the findings of a study of 103 home care workers who have cared for PWAs. It investigated degree of "exposure" to AIDS cases, perception of risk of occupational contagion, client/worker relationships, attitudes toward homosexuality and drug abuse and other work related factors for their relationship with psychological morale and job satisfaction. Multivariate analyses found sociodemographic characteristics and physical health to be the strongest predictors of morale. The quality of client/worker relationships and risk perception were the strongest predictors of job satisfaction. These findings, and that of the relative lack of importance of exposure to AIDS cases and attitudes toward the risk groups in accounting for job satisfaction, are discussed in terms of qualitative data collected from respondents during informal small group discussions. PMID- 1595294 TI - Women's employment, social support, and mortality. AB - This study uses a longitudinal design to examine the extent to which social support at work is protective against death and the degree to which it explains mortality differences between employed women and those not in paid employment. Women's total role responsibilities and community involvement, as an alternative source of social support and social integration, are also considered in the analysis. The outcome examined is mortality risk over a 15 year period. The 1140 women included in this study were randomly selected from among members of a large HMO and were part of a household interview conducted in 1970-71. Medical and vital records for 15 years post interview period are linked with the survey data. The results of this analysis suggest that social support at work is protective against mortality among employed women and contributes to mortality risk differences between employed and nonemployed women. While the relative hazard of death for nonemployed women who have some community involvement is greater than for employed women, the difference is not statistically significant. Community involvement may provide an alternative, albeit weaker, avenue for gaining some of the same advantages available in paid employment. Future research directions are discussed. PMID- 1595295 TI - Women in clerical jobs: spousal role satisfaction, stress, and coping. AB - Little is known about the qualitative components of women's multiple roles or about women's perceptions and subjective feelings about their occupational and domestic roles, although all of these factors modulate health outcomes. The research upon which this manuscript is based was designed to respond to the need for understanding the daily experiences of women in clerical jobs. The data about spousal role satisfactions, stress and coping strategies, as perceived and articulated by them, indicates there are almost an equal number of satisfying and stressful aspects of the spousal relationship. Examples of the satisfying aspects are companionship, reciprocity, and interaction; while stressful aspects are inequality of tasks, disagreements and domination. Women in this study cope by using strategies that are more solitary in nature. They identify very little power to negotiate support and tangible assistance. PMID- 1595296 TI - Occupational stress, social support, and depression among black and white professional-managerial women. AB - This study employed a quota sample of 200 black and white professional-managerial women from the Memphis, Tennessee, area to explore the relationships among occupational stress, social support, and well-being. Data were gathered through face-to-face, focused life history interviews. Depression was measured using the Center for Epidemiologic Studies Depression Scale (CESD). Social support for one's career was assessed from three sources: family, friends, and co-workers, and measures of occupational stress included workload, unfair/impersonal treatment, and trouble with boss or subordinates. Using multiple regression techniques, the findings of this study indicate that there are complex differences in levels of social support, occupational stress, and depression across social structural dimensions (race, class background, supervisory status, marital status, parental status) for this sample, including significant two-and three-way interactions. Trouble with boss or subordinates was also found to be related to levels of depression. Career support from friends, co-workers, and family, on the other hand, did not directly benefit the women's well-being or lessen the damaging effects of interpersonal job conflict on their mental health. PMID- 1595297 TI - Assessing health care delivery to male versus female veterans. AB - The study reported was undertaken to explore allegations that women veterans have not received the quality of care in the Department of Veterans Affairs (VA) that is typical of that being received by their male counterparts. The study consisted of a chart review of male and female inpatients (n = 114) and telephone interviews with a subsample of these veterans (n = 55) treated at a large metropolitan VA hospital. Overall, chart documentation was poor, regardless of gender. On average, two-thirds of males and females receive regular gender specific examinations, although the number is somewhat lower for females. Both women and men were quite satisfied with the care they received. Future studies should focus on the evaluation of workable solutions to providing equitable health care to women veterans that are already in operation. PMID- 1595298 TI - The parental leave debate: implications for policy relevant research. AB - Legislative activity regarding parental and family medical leave has been intense, with heated debate, in both national and state political arenas. Proponents of legislation report that policy is needed because of women's increasing rate of labor force participation and the concomitant shortage of substitute infant care. Benefits of policy are presumed to include women's health and parent-child bonding. However, no direct empirical evidence exists to support these assumptions. Opponents of legislation say that the cost of policy is burdensome to employers. However, the General Accounting Office reports that the only measurable net costs to employers associated with the federal bill will be to cover the leave takers' health insurance premiums. This literature review examines the above issues and identifies a policy relevant research agenda, crucial to the development of rational and humane policy. PMID- 1595299 TI - [The lung as a reflection of internal medicine diseases]. AB - The lungs are called "mirror of internal medicine" because they are often involved in multisystem diseases. The morphologic changes of the lungs are uncharacteristic and the classification is only possible in relation to other manifestations of multisystem diseases. In this article clinical syndromes with pulmonary manifestations will be reviewed. Congestive heart failure and congenital diseases may lead to pulmonary features. Most cardial pleural effusions are transudates except postcardiac injury syndrome causes pleural exsudates. Almost all connective tissue diseases may affect the lungs and the pleura. Scleroderma, systemic lupus erythematodes, vasculitis, polymyositis, Sharp's syndrome, Wegener's granulomatosis, Goodpasture and Sjogren's syndrome, rheumatoid arthritis, ankylosing spondylitis and sarcoidosis are discussed. There is an association of gastroesophageal reflux and asthma. Acute pancreatitis may cause an adult respiratory distress syndrome. Endocrine and hematologic diseases seldom cause pulmonary changes. Many malignant tumors are going along with metastasis in the lungs. Renal insufficiency causes "fluid lung", nephrotic syndrome pleural effusions. Finally different drugs induce pulmonary diseases. PMID- 1595300 TI - [Results of the Berlin HOT/UVB comparative study in patients with peripheral arterial occlusive disorders]. AB - Both photobiological methods haematogenic oxydation therapy (HOT) and therapy by retransfused ultraviolet irradiated own blood (UVB) were compared with regard to its therapeutic efficacy in patients with peripheral arterial occulusive disease of lower extremities in stage II by Fontaine. In parallel to paraclinical and coagulation data, haemodynamic as well as haemorheological parameters were investigated to clarify possible mechanisms of action of these therapies. 15 male patients were enclosed in the corresponding patients groups with a mean walking distance of 178 +/- 108 m (HOT) and 213 +/- 147 m (UVI), respectively. The claudicatio-distances were significantly improved after 10 series of therapy by 94% in the HOT-group and by 83% in the UVI-group, respectively. A significant difference in the improvement of walking distances could not be detected between both therapeutical methods. Significant alterations in observed paraclinical parameters were not observed. PMID- 1595301 TI - [Immunologic studies in patients with dilated cardiomyopathy]. AB - In 10 cases of dilated cardiomyopathy the HLA-loci (A, B, C, DR) and marker expression on lymphocytes were studied. In this group the T4/T8-ratio was decreased and interleukin-2-expression was increased in relation to normals or patients with chronic coronary heart disease, respectively. 9 patients had the HLA-A1 or HLA-A2-locus in their siblings. In correlation analysis between immunological and hemodynamic parameters a good correlation of the number of NK cells to the ejection fraction (r = 0.79) and negative correlation of helpercells (CD4) to the cardiac output were found (r = -0.80). The results of this attempt suggest an immunological pathogenesis of the dilated cardiomyopathy. PMID- 1595302 TI - [The Schaarschmid brothers. On the 200th anniversary of the death of August Schaarschmid (1720-1791)]. AB - The 200th anniversary of the death of August Schaarschmid is the occasion to remember the life and work of this university teacher in connection with life and work of his brother Samuel Schaarschmid. The two temporarily taught at the Berlin Collegium medico-chirurgicum and in the Prussian capital they above all worked in the field of the surgical training. Later on August Schaarschmid changed to the Mecklenburg Academy of Butzow. The edition of a wide-spread special periodical as well as of a series of much used teaching tables belongs to the lasting merits of the brothers Schaarschmid whose eventful fate should be described here. PMID- 1595303 TI - [Is preventive sclerotherapy of esophageal varices sensible--useless- dangerous?]. PMID- 1595304 TI - [Breast cancer screening: current status and introduction as a preventive service]. AB - 1. Screening intervals according to Tabar: 1 year in women younger than 50 in order to minimize "interval cancers". 2 years in women older than 50 years. 2. Mammographic views according to Lundgren et al: 2 views at first round 1 oblique view in the following rounds, yearly. All women on risk should attend screening. The identification of useful "high risk groups" is not established. Palpation is recommended at each screening. Self-examination is recommended. Adjuvant therapy should not depend on lymph node status in screening-cancer cases. It should depend on clinical and histological "prognostic factors". PMID- 1595305 TI - [Diabetes and pregnancy--optimal management]. AB - Current classification, diagnostic and therapeutic guidelines of diabetes in pregnancy are briefly reviewed in this paper. Obstetricians mainly are confronted with the insulin-dependent diabetic (IDDM) prior to conception and during pregnancy. Intensive interdisciplinary co-operation is considered a prerequisite for treatment of the diabetic patient planning or carrying a pregnancy. The following subspecialties should work together in diabetic pregnant care: Reproductive Medicine incl. high-level endocrinological diagnostics, Diabetology with a teaching facility, and--within a perinatal center--an obstetric and neonatal department experienced in diabetic care. Preconceptional metabolic adjustment as well as surveillance of fetal and maternal condition during the first trimester of pregnancy are considered the mainstay in diabetic patient's care. Possible complications of diabetic pregnancy are described. Only in rare cases, pregnancy is contraindicated because of retino- or nephropathy. The screening program for gestational diabetes is based upon the patient's history, fasting-blood-glucose-levels, 50-g-oral-glucose-tolerance-test (OGTT) and a 24-h blood-glucose-profile. Measurement of insulin levels in amniotic fluid are recommended for cases that remain yet undiagnosed. PMID- 1595307 TI - [Single umbilical artery--consequences of prenatal diagnosis]. AB - The authors report about the prenatal diagnosis of 34 cases of fetuses with a single umbilical artery (SUA) observed at the Perinatal Center of Charite. Between January 1989 and June 1991 the SUA has been associated with some adverse perinatal events, such as low birth weight (35%), congenital malformations (35%), perinatal mortality (11%) and placental alterations (76%). The incidence was not higher in girls than in boys. We did not find any chromosomal anomalies in our cases. An accurate ultrasonographic examination of the SUA in the 16th to 20th week is very important. The prognosis of the newborn could be improved by efficient diagnosis and optimum management of pregnancy and of delivery at a perinatal center. PMID- 1595306 TI - [Analysis of lymph node status and lymph node morphology in cervix cancer operated by the Wertheim-Meigs-Okabayashi method]. AB - We evaluated in the histologic labor, of the Department of Obstetrics and Gynaecology of the Tubingen University 133 specimens of cervical carcinomas stages I and II operated on according to Wertheim-Meigs-Okabayashi. Topic of this analysis is lymph node status, concomitant alterations and lymphangiosis carcinomatosa. On the average 22.1 lymph nodes (1-58) have been removed. 12.8 per cent of cervical carcinomas had metastases, on the average 3 ones. 78.6 per cent of the metastases were localized in nondilymphatici interiliaci, 14.3 per cent in nodi iliaci communes. 5-year survival with metastases was 70.6 per cent, without 90.5 per cent. Over all a lymphangiosis carcinomatosa in 20.3 per cent was detectable. In 59.9 per cent of the lymph node metastases additionally a lymphangiosis carcinomatosa was present, on the contrary only 9.9 per cent of tumour-free ones. 5-year survival with lymphangiosis carcinomatosa was 70.4 per cent and 92.4 per cent without. Regressive changes, mostly as vacat fat, were observed in like the same percentage both in tumour positive and tumourfree lymph nodes. PMID- 1595309 TI - [Severe hydrops fetalis in a first trimester pregnancy with Ulrich-Turner syndrome]. AB - We report about a case of abundant hydropic evolution of a fetus in the first trimester of gestation. Already in the 8th week of gestation we diagnosed the first references of failure with transvaginal ultrasound. In the following three weeks we observed the progression of the hydrops. The genetic research of fetal tissue after induced abortion show the karyotype 45 X0. PMID- 1595308 TI - [Clinical aspects and pathology of granulosa cell tumors. A single case report]. AB - Case report on a granuloma cell tumour in a 82 year old patients. Because of estradiol production postmenopausal bleedings from a adenomatous-hyperplastic endometrium had been in the history. Hormonal values became normal following removal of the benign tumour in stage I. The most important pathologic, endocrinologic and therapeutical principles of the tumour have been described. PMID- 1595310 TI - [Eduard Arnold Martin (1809-1875)--founder of the Berlin Gynecologic Society. A contribution to the history of the Berlin Society of Obstetrics and Gynecology. II]. AB - In 1844 the society of obstetrics in Berlin was founded by Carl Mayer (1795 1868). In 1873 this society splits in the society of obstetrics and the society of gynaecology. The present paper demonstrate the biography of Eduard Arnold Martin (1809-1875), the founder of the gynaecological society in Berlin (1873) and also his importance in the creation of an modern gynaecology. PMID- 1595311 TI - [7th Congress: "The fetus as patient", 24 to 26 August 1991 in Bonn]. PMID- 1595312 TI - Intrathoracic meningocele presenting as a mediastinal mass lesion. Case report. AB - A routine chest X-ray in a 52-year-old man revealed a widening of the posterosuperior mediastinum and the patient was hospitalized on the suspicion of having a mediastinal mass lesion. Further investigations revealed an anterior cervicothoracic meningocele (intrathoracic meningocele), the dural herniation passing through two large midline congenital openings of the C7-T3 vertebral bodies which appeared partially fused and associated with other regional skeletal malformations. PMID- 1595313 TI - Congenital lumbosacral lipomas presenting as a form of occult spinal dysraphism. A report of 9 surgically treated cases. AB - Nine cases of congenital lumbosacral lipoma have been diagnosed and treated surgically at the Hacettepe University School of Medicine, Department of Neurosurgery during the last 16 years. Five patients were male and four female with ages ranging from 18 months to 30 years. The most frequent complaints were mass in the back (in five cases), motor weakness in the lower extremities (in five), urinary incontinence (in five), and lumbosacral hypertrichosis (in five). On neurological examination, four patients had deep tendon reflex changes, five had motor changes and four were normal. There was significant improvement in seven cases. Two had no improvement. In this report, we review nine patients retrospectively, and discuss the surgical intervention and the results achieved. PMID- 1595314 TI - On early surgery of hydrocephalus in low-birth-weight infants. AB - The paper weighs the indication and the timing of surgery in hydrocephalus mostly due to ventricular haemorrhage in premature infants with an average of 31 weeks of gestational age and of 1.409 g average birth weight. The authors suggest to wait with the intervention until the intraventricular haemorrhage has subsided because the hypertension may often cease when the CSF is not bloody anymore. In case of a progressive process they gained favourable results with early surgery. They give a detailed account about the choice of the various shunts, list eventual complications, the US and CT controls. PMID- 1595316 TI - [From the beginnings of pediatric neurosurgery. "Hans-Werner Pia Memorial Lecture" 20 November 1991 in Bad Nauheim]. PMID- 1595315 TI - [A rare complication of shunt therapy. Metastasis of brain tumors by cerebrospinal fluid drainage]. AB - Shunting of cerebrospinal fluid to extracranial spaces has been a common and effective procedure for symptomatic therapy of hydrocephalus since the fifties. In 1954 the first spreading of tumor cells via a ventriculo-pleural shunt was reported. We are presenting a case of a 10 month old girl with a medulloblastoma of the lower brain stem with spreading of the intracranial tumor through a ventriculoperitoneal shunt. Further 43 cases of the world literature with shunt associated metastasizing of brain tumors are analysed. The extraneural spreading of tumor cells through shunt tubes must be considered as a possible complication of the shunting procedure. PMID- 1595317 TI - [Hemostasis in neurosurgical operations. A comparative study between collagen fleece (Lyostypt) and a gelatine sponge (Marbagelan)]. AB - A study of 100 patients each with neurosurgical operations is reported, in which a prospective randomized and controlled investigation compares two haemostyptic agents, Marbagelan and Lyostypt. Collagen fleece was found superior to gelfoam as to haemostasis although slightly less convenient in application. Postoperative complications specific to the haemostyptic agents were not seen. PMID- 1595318 TI - Hemangioblastoma during pregnancy. Case report. AB - A 20-year-old pregnant woman (8th month of gestation) developed signs of intracranial hypertension and coordination disorders. The CT examination demonstrated hydrocephalus, occlusion of the IV ventricle and hyperdense mass lesion in the right cerebellar hemisphere. Following ventricular drainage cesarean section was performed and then total removal of cerebellar hemangioblastoma, which resulted in rapid and complete reversal of neurological abnormalities of the mother and the child. PMID- 1595319 TI - [Is there an unusual incidence of the manifestation of intracranial angiomas in pregnancy? Risk assessment based on 17,733 patients over 10 years]. AB - From 1979-1988, 134 inpatients (m:f = 80:54) were treated because of an intracranial angioma (AVM). The male/female ratio was 3/2 in general as well as during the "reproductive age" (15-45 yrs). In 6 patients (20-27 yrs; grav 2/para 1: n = 3; grav 1/para 0: n = 3) the AVM became symptomatic during pregnancy (n = 4: 23-33 gestational week) or at birth (n = 2). In the group of the presently non pregnant women (n = 40) 47 uncomplicated deliveries had occurred years before. We conclude that the available data neither allow us to reject nor to confirm the hypothesis that pregnancy and/or delivery influence the manifestation of cerebral AVMs. The reasons for this dilemma of epidemiology are discussed. PMID- 1595320 TI - [Significance of EEG findings in craniosynostosis]. AB - Literature of the topic is reviewed and own findings of 80 patients with turricephaly and 38 with dolichocephaly are exhibited. Striking was the increased frequency of spike potentials, 8,8 resp. 16% (SW 5%). Genetical connection between causes of premature synostosis and increased associated epilepsy resp. spike potentials is supposed. In cases of craniosynostosis associated with epileptic fits the EEG remains further irreplaceable, moreover it is useful in the assessment of cerebral functioning prior to surgical intervention. PMID- 1595321 TI - Calcitonin gene-related peptide-containing neurons supplying the rat digestive system: differential distribution and expression pattern. AB - In the enteric nervous system, calcitonin gene-related peptide (CGRP) immunoreactivity is localized to a substantial number of capsaicin-sensitive afferent fibers and to intrinsic neurons and processes. CGRP immunoreactivity detected by immunohistochemistry represents the expression of two distinct genes, the calcitonin/alpha-CGRP and the beta-CGRP genes, which have different tissue distributions. In the present study, we used (1) in situ hybridization histochemistry and ribonucleic acid (RNA) blot hybridization with RNA probes complementary to the divergent sequences of alpha- and beta-CGRP messenger RNAs (mRNAs) to differentiate which CGRP gene was expressed in enteric and afferent neurons; and (2) axonal transport approaches in combination with CGRP immunohistochemistry to define the location of CGRP-containing afferent neurons supplying the digestive system. In situ hybridization histochemistry with [35S] labeled RNA probes indicated that in the gastrointestinal tract beta-CGRP mRNA, but not alpha-CGRP mRNA, was expressed in enteric neurons confined to the myenteric and submucous plexuses of the small and large intestine. In dorsal root and vagal sensory ganglia, mRNAs for alpha-CGRP and beta-CGRP were both present in a vast population of neurons, with an overlapping pattern, even though the alpha-CGRP signal appeared more intense. RNA blot hybridization analysis showed a single band of hybridization at 1.2 Kb with the beta-CGRP RNA probe in RNA extracts from muscle layer-myenteric plexus and submucosal layer preparations of the ileum, and from dorsal root ganglia; it also showed a single band at 1.3 Kb with the alpha-CGRP RNA probe in extracts from dorsal root ganglia, but not from the intestine. These findings further support the differential expression of alpha- and beta-CGRP mRNAs. Retrograde transport of fast blue or fluorogold coupled with CGRP immunohistochemistry demonstrated that the vast majority of CGRP-containing afferent neurons supplying the stomach, proximal duodenum, and pancreas were located in dorsal root ganglia at the middle and lower thoracic and at the upper lumbar levels, and represented a major component of the afferent innervation of these viscera (up to 89%). Approximately 50% of CGRP immunoreactive afferent neurons also expressed tachykinin (TK) immunoreactivity, as shown by triple labeling. Only a minor component of the afferent innervation of the stomach, duodenum, and pancreas derived from vagal CGRP-containing neurons (less than 8%). A large portion of these neurons (an average of 62%) also contained TK immunoreactivity.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1595322 TI - Altered precision grasping in stumptail macaques after fasciculus cuneatus lesions. AB - Patterns of precision grasp are described in stumptail macaques (Macaca arctoides) before and after lesions of the fasciculus cuneatus (FC). Three monkeys were videotaped while reaching for and grasping small food items. From these videotapes, records were made of the style and outcome of each grasp. Kinematic measurements were also made to describe grip formation and terminal grasp. During grip formation, grip aperture was measured as the distance between the tips of the index finger and the thumb. For terminal grasp, the joint angles of the index finger were measured. The majority of grasps by normal monkeys were of the precision type, in which the item was carried between the tips of the index finger and thumb. Each normal monkey approached objects with a highly consistent grip formation; that is, the fingertips formed a small grip aperture during the approach, and the aperture varied little on repeated grasps. To grasp an item, the forefinger moved in a multiarticular pattern, in which the proximal joint flexed and the distal joint extended. As a result of this combination of movements, the forefinger pad was placed directly onto the object. Following FC transection, the monkeys were studied for 10 months, beginning 1 month after the lesion, to allow for recovery from the acute effects of surgery. The monkeys could grasp the food items, but they rarely opposed the fingertips in precision grasp. Grip formation was altered and was characterized either by excessive grip aperture or by little to no finger opening. All of the monkeys used the table surface to help grasp items. Combined multiarticular patterns of flexion and extension were never observed postoperatively; they were replaced by flexion at all joints of the fingers. These results suggest that the FCs are more important for precision grasping than for other, less refined grasp forms (e.g., power grasps; Napier, 1956). The FCs provide critical proprioceptive feedback to cerebral areas involved in the planning and/or the execution of these movements. PMID- 1595324 TI - Treatment of 46 patients with Turner's syndrome with recombinant human growth hormone (YM-17798) for three years: a multicentre study. AB - A total of 46 patients with Turner's syndrome were treated for three years with recombinant hGH. Nineteen patients received hGH at a weekly dosage of 0.5 IU.kg 1.week-1, while 27 received 1.0 IU.kg-1.week-1 by daily sc injection. Both treatment groups showed a statistically significant growth increase during treatment. The increase in height over three years' treatment, as expressed by SD score (SDS) for chronological age, did not differ significantly between patients treated with 0.5 IU and those with 1.0 IU hGH. Seventeen of 22 patients over the age of 14 had exceeded their expected adult height. Plasma IGF-1 levels were elevated and no remarkable advances in bone age were observed during the treatment in either treatment group. There were no other significant changes in physical or laboratory examinations. No glucose intolerance was observed. These results indicate that hGH treatment is useful for accelerating growth velocity in patients with Turner's syndrome. However, further study will be required to find the best treatment dosage. PMID- 1595323 TI - Alterations of natural hand movements after interruption of fasciculus cuneatus in the macaque. AB - As part of a series of investigations on the control of fine finger movements in the macaque, spontaneous use of the hand in grooming, scratching, and manipulation was observed before and after interruption of fasciculus cuneatus (FC). Videotaped observations were made of four stumptail macaques (Macaca arctoides) living outdoors in social groups. The monkeys were followed for 1 to 3 years postoperatively. For the first 2 weeks following surgery, all monkeys neglected the affected hand and did not use it for support, locomotion, climbing, scratching, foraging, or grooming. Recovery of gross arm and hand movements occurred over a 1- to 3-month period. All the monkeys eventually used the hand for support, climbing, and object manipulation, but fine control of the fingers did not recover. Also, there was an apparent hypotonia of the fingers, imparting a "floppy" appearance to the hand. The animals coped with the loss of fine control by decreasing the frequency of some behaviors, eliminating others, and developing alternative strategies. Exploratory movements that were utilized for investigating the anogenital area or foraging for small food items were eliminated by FC interruption. There were obvious deficits in grip formation and grasp of small food objects (see Glendinning et al., this issue), but effects on similar movements during grooming only became obvious after repeated inspection of videotaped records. Self-scratching and sweeps of the hand in grooming were preserved but altered in form and frequency. The component movements in these behaviors were relatively uncoordinated, and the fingers were splayed (abducted). Often the hand was formed in a rigid posture throughout the sweeping motion, and the fingers did not stroke the skin individually. Frame-by-frame analysis of videotapes revealed that the morphology of the precision grip during grooming, in movements termed "plucks," was permanently altered. Preoperatively, the monkeys kept the index finger and thumb closely apposed and routinely made contact on the distal surfaces of the digits, as has been described for precision grip in humans. Postoperatively, this relationship was altered. The index finger frequently missed the thumb tip and made contact on the proximal part of the phalanx, or missed the thumb altogether. Thus, the dorsal column input is important for proprioceptive guidance of movements that achieve "tactile foveation," when objects or surfaces are actively contacted by the receptive areas of keenest sensitivity (on the fingertips). PMID- 1595325 TI - Biogenic amines and thyrotoxicosis. AB - Circulating levels of T3, T4, gamma-amino-butyric acid, glutamate, 5 hydroxytryptamine, histamine, monoamine oxidase and histaminase were studied in 45 (25M, 20F) hyperthyroid patients and 46 (25M, 21F) normal healthy volunteers. Increased levels of blood 5-hydroxytryptamine, histamine and glutamic acid were observed along with elevated T3 and T4, whereas plasma gamma-aminobutyric acid, monoamine oxidase and histaminase activities were found to be low in both male and female patients. After three months of treatment, circulating levels of 5 hydroxytryptamine, histamine and glutamic acid decreased significantly along with normalization of thyroid hormones and with an increase in the concentrations of gamma-aminobutyric acid, monoamine oxidase and histaminase. There was a positive correlation between these amines and thyroid hormone levels. The findings thus suggest that alterations in the metabolism of biogenic amines may be related to an altered metabolism in thyrotoxicosis, and these parameters may prove to be useful markers for diagnosis and follow-up of these patients. PMID- 1595326 TI - Calcitonin release from medullary thyroid carcinoma by thyrotropin-releasing hormone: comparison with calcium injection. AB - The effects of thyrotropin-releasing hormone on the release of calcitonin were investigated in 15 normal subjects and 12 patients with medullary thyroid carcinoma. The present study also compared the effect of TRH stimulation with calcium infusion test on calcitonin release in patients with medullary thyroid carcinoma. In normal subjects, calcitonin increased from a basal value of 7.5 +/- 2.5 pmol/l to a peak value of 9.4 +/- 3.0 pmol/l (p less than 0.01) after iv injection of synthetic TRH (500 micrograms). Basal calcitonin values in patients with medullary thyroid carcinoma were high (1216 +/- 2230 pmol/l, p less than 0.05), and TRH induced a further increase in calcitonin to 1842 +/- 3149 pmol/l in all the patients (p less than 0.05). They had a peak value of 7891 +/- 13,528 pmol/l after the calcium infusion, which was significantly higher than the basal value of 1463 +/- 2630 pmol/l (p less than 0.05). All medullary thyroid carcinoma patients displayed a marked calcitonin increase after TRH and calcium stimulation. Although the increase in serum calcitonin after TRH injection was lower than that after calcium injection (1.6-fold vs 5.4-fold, p less than 0.05), there was no significant difference in mean peak calcitonin value following TRH and calcium injection in patients with medullary thyroid carcinoma. These results indicated that TRH could stimulate calcitonin release from the thyroid C-cells in both normal subjects and patients with medullary thyroid carcinoma. PMID- 1595327 TI - Progesterone, testosterone and estradiol-17 beta inhibit gonadotropin-releasing hormone stimulation of G protein GTPase activity in plasma membranes from rat anterior pituitary lobe. AB - In order to understand the biochemical mechanisms underlying the rapid, non genomic effects of gonadal steroids on gonadotropin secretion, we examined the effects of progesterone, testosterone and estradiol-17 beta on the low Km GTPase activity associated with transducer G proteins coupled to gonadotropin-releasing hormone (GnRH) receptors. Homogenates of anterior pituitary lobes from adult male rats were processed by discontinuous sucrose gradient centrifugation to isolate plasma membranes. The low Km GTPase activity (EC 3.6.1.-) was assayed in 5 micrograms membrane protein using [gamma-32P]GTP at 37 degrees C in an ATP regenerating buffer containing 1 mumol/l unlabeled GTP. One hundred nmol/l each of progesterone, testosterone and estradiol-17 beta maximally stimulated low Km GTPase activity by 61%, 59% and 45%, respectively (p less than 0.05). Time course studies revealed that 100 nmol/l progesterone stimulated the enzyme activity by 93% and 62% at 5 and 30 min, respectively; 100 nmol/l testosterone stimulated GTPase activity by 100% and 72% at 5 and 30 min, respectively; 100 nmol/l estradiol-17 beta stimulated GTPase activity by 80% and 70% at 5 and 30 min, respectively. GnRH stimulated the low Km GTPase activity by about 60% in a concentration-dependent manner. In the presence of the gonadal steroids, the ability of GnRH to stimulate the GTPase activity was inhibited. For example, stimulation ranged from 36% to 60% with 0.1-100 nmol/l GnRH alone, but only from 7% to 20% in the presence of GnRH and 100 nmol/l progesterone (p less than 0.05). Similarly, in the presence of 100 nmol/l estradiol-17 beta, GnRH stimulation of the enzymatic activity ranged from 12% to 19%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595328 TI - Changes in plasma vasopressin concentration and plasma osmolality in relation to age and time of day in the male Wistar rat. AB - The influence of age on several parameters related to water balance was studied in Wistar rats. Plasma AVP concentration and plasma osmolality were increased at midday in 21-month-old rats as compared with 3- and 4-month-old rats. Daily water intake per 100 g body weight was reduced in 14- and 21-month-old rats as compared with 3- and 4-month-old rats, but total water intake was unaltered. These results suggest that there is a change in water balance in Wistar rats with age. In order to obtain information about the influence of age on daily fluctuations in plasma AVP concentration and osmolality these parameters were determined in 4-month-old Wistar rats sacrificed at 2 h intervals during the day and in 20- and 31-month old rats sacrificed at 8 h intervals. Plasma AVP concentrations were low during the light period and high during the dark period in 4-month-old rats. The relationship between plasma osmolality and plasma AVP concentration was dependent on the time of day in 4-month-old-rats. Plasma AVP concentrations were higher at 16.00 than at 08.00 and 24.00 in 20-month-old rats, and higher at 24.00 than at 08.00 and 16.00 in 31-month-old rats. In contrast to the plasma AVP concentration during the light period, the average daily AVP concentration (average of plasma AVP concentrations at 08.00, 16.00 and 24.00) was increased in 31-month-old rats only. The relationship between plasma osmolality and plasma AVP concentration was not age-related.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595329 TI - A circadian rhythm in adrenal responsiveness to ACTH is not confirmed by in vitro studies. AB - From in vitro studies a circadian variation in adrenal gland response to ACTH was observed. Regulation of this circadian rhythm in adrenal responsiveness was localized to the cellular level; involving variation in either receptor density or affinity. In the present study the circadian variation in adrenal gland responsiveness was studied using an in vitro approach. Levels of corticosterone secretion during the active and inactive phases were determined using incubated rat adrenal slices in the presence and absence of submaximal stimulation by the synthetic ACTH peptide, ACTH(1-24). Initially, a circadian difference in adrenal responsiveness appeared to exist in all groups except the betamethasone pretreated. However, data expressed in terms of corticosterone secretion/mg adrenal weight proved to be misleading due to the presence of an apparent circadian pattern in adrenal gland weight; the adrenal glands from animals in the dark being significantly less in weight than those from animals in the light phase. When the data were expressed in terms of actual gland output, no circadian variation in adrenal response to exogenous ACTH(1-24) stimulation was apparent. In conclusion, the present study does not support the concept of a circadian variation in the adrenal response to ACTH(1-24) stimulation resulting from a variation in the responsiveness of the adrenal cells themselves. However, the present study does not preclude the possibility of a circadian variation due to modulation of adrenal responsiveness by humoral factor(s) other than ACTH. PMID- 1595330 TI - Evidence for the presence of endogenous 19-nortestosterone in the cow peripartum and in the neonatal calf. AB - Urine samples were collected from five Brown Swiss cows during the 18 days prior to and 11 days after parturition and were analysed for 19-nortestosterone using an enzyme immunoassay. Nortestosterone concentrations ranged from 70 to 130 nmol/l in all samples taken before parturition. The levels declined within two days, and 11 days post partum no nortestosterone was detectable. In urine from newborn calves, maximal nortestosterone concentrations were determined during the first day of life (10.9-120 nmol/l), declining below 7.3 nmol/l until day 3 in most animals and remaining below the detection limit (less than 3.6 nmol/l) after day 8 in all animals. There was no obvious difference between cows carrying a male or a female calf nor between newborn male or female calves. Using the combined methods high performance liquid chromatography/enzyme immunoassay and high performance liquid chromatography/gas chromatography-mass spectrometry, the immunoreactivity in urine was identified to be 19-nortestosterone-17 alpha. Although there is unequivocal evidence for the endogenous production of nortestosterone in pregnant cows, its function for placenta physiology, pregnancy anabolism and parturition remains unclear. However, new threshold levels for residue control of nortestosterone need to be fixed in accordance with the endocrine status of the animals. PMID- 1595331 TI - Thyroid hormone responsiveness of the L1210 murine leukemia cell line. AB - The presence of saturable and high affinity 3,5,3'-triiodothyronine (T3) binding sites was demonstrated in L1210 murine leukemia cell nuclei. Scatchard analysis revealed one class of receptors for T3 with Ka = 2.187 x 10(9) l/mol and a maximum binding capacity (Bmax) of 3.96 fmol/10(6) cells. The effects of T3 on protein phosphorylation and growth rate of L1210 cells were investigated in a medium containing T3-depleted fetal calf serum. T3 was observed to be effective in enhancing protein phosphorylation (153.06% +/- 5.99 SD) compared to cells grown in the absence of T3 (81.49% +/- 13.50 SD). Moreover, in the presence of high T3 concentration (11.15 nmol/l) T3 was found to significantly increase the cell growth rate. In addition, the T3 receptor-associated alterations during the cell cycle, as measured by flow cytometry, suggest that the presence of T3 receptors becomes evident during the late G1 phase of the cell cycle, and T3 receptor numbers increase during the S phase. These results suggest that in in vitro conditions representing high T3 concentration, the number of L1210 leukemia cells may be increased by T3 via nuclear receptors. The L1210 leukemia cell line may serve as a convenient tool for in vitro studies of nuclear receptors and/or mechanism of action of T3. The binding affinity of T3 receptors is similar to that found in rat hepatocytes or human lymphocytes. PMID- 1595332 TI - Lipid peroxidation in early experimental diabetes in rats: effects of diabetes and insulin. AB - The degree of lipid peroxidation was measured in organs from diabetic rats receiving no treatment, and in those from insulin-treated diabetic rats and controls. Lipid peroxidation was measured as organ content of malondialdehyde, a degradation product of polyunsaturated fatty acids. In the kidney, lipid peroxidation was increased after one week of diabetes; insulin treatment reduced the level of lipid peroxidation to levels lower than seen in controls. In the liver, diabetes caused an increased lipid peroxidation, which could be reversed by insulin; no additional effect of insulin was found. In heart and pancreas no effects of diabetes or insulin were demonstrated. The present paper provides evidence that lipid peroxidation is increased in the early stages of experimental diabetes and is reversible by insulin treatment. Hyperinsulinaemia may, in itself, counteract lipid peroxidation in kidney. PMID- 1595333 TI - Technical problems associated with the use of 32-gauge and 22-gauge spinal catheters. AB - Interest in the use of continuous spinal anaesthesia (CSA) has recently increased because of the availability of new, extremely thin catheters. In this study the use of 32-gauge (G) catheters was compared with 22-G catheters in operations on the lower limb and for the administration of intrathecal morphine in the postoperative period in 42 elderly patients. CSA succeeded in 34 cases and 8 patients were anaesthetised with a single-shot spinal method. No general anaesthesia was needed. Technical problems with the subarachnoid puncture with the 19-G needle caused two failures in the 22-G group. In a group of 20 patients, there were five failures with the 32-G catheter, as opposed to one failure with the 22-G catheter in a group of 20 patients. Associated with morphine injection through the 32-G catheter, the syringe or connector was inadvertently disconnected in four cases and a tear of the catheter wall was observed in one case. Such problems did not occur with the 22-G catheter. Postdural puncture headache did not occur, and there was no difference in the incidence of patient reported postoperative complications between the two groups. It is concluded that both the insertion and maintenance of the thin (32-G) subarachnoid catheters are associated with more technical problems than the 22-G catheter. PMID- 1595334 TI - Pharmacokinetics of clonidine after epidural administration in surgical patients. Lack of correlation between plasma concentration and analgesia and blood pressure changes. AB - The pharmacokinetics of epidural clonidine 150 micrograms was studied in 13 patients who had undergone abdominal hysterectomy. Plasma clonidine concentrations were measured up to 19 h in eight patients. In another five patients frequent blood sampling was performed only during the first 20 min to define early vascular uptake better. Peak plasma clonidine concentrations of 1.08 +/- 0.35 ng ml-1 (mean +/- s.d.) were reached between 5 and 10 min after injection. Plasma elimination half-life was 829 +/- 157 min and plasma clearance was 177 +/- 28 ml min-1. There was a significant decrease in arterial blood pressure within 10 min of the injection of clonidine. The maximum decrease in systolic blood pressure, from a pre-injection value of 135 +/- 24.7 to 99 +/- 14.4 mmHg (18.0 +/- 3.3 to 13.2 +/- 1.9 kPa), occurred at 60 min. Blood pressure remained significantly lower than the pre-injection value for 4 h. There was no change in heart rate. Verbal analogue pain scores, on a scale 0-10, decreased from a median of 7.6 before clonidine to 5.0 after 30 min (P less than 0.05). The median score at 60 min was 4.3. Thereafter, pain scores were not significantly different from the control score. We conclude that epidural clonidine 150 micrograms produces only moderate and short-lived postoperative analgesia. Absorption of clonidine from the epidural space into the blood is very rapid and may contribute to the hypotension that occurs. PMID- 1595335 TI - Influence of positive end-expiratory pressure on extravascular lung water during the formation of experimental hydrostatic pulmonary oedema. AB - The influence of positive end-expiratory pressure (PEEP) on extravascular lung water measured with the double-indicator dilution technique (EVLWi) has been studied during formation of hydrostatic pulmonary oedema in a canine model. The oedema was created by elevating the mean pulmonary artery pressure (PAP) to 30 mmHg (4.0 kPa) by inflation of a left atrial balloon, and a simultaneous intravenous saline infusion of 15 ml.kg-1.h-1. All dogs were ventilated with zero end-expiratory pressure (ZEEP) until the initial EVLWi had increased by 50%. In one group (n = 5) a PEEP of 10 cmH2O (1.0 kPa) was applied and the dogs were studied for a further 4 h and in the other group (n = 5) ZEEP was maintained throughout the study. During the first 2 h after ZEEP/PEEP application EVLWi increased from 13.7 +/- 2.1 to 20.2 +/- 1.2 ml.kg-1 with ZEEP ventilation and from 13.6 +/- 1.2 to 18.6 +/- 1.9 ml.kg-1 with PEEP ventilation. EVLWi remained unchanged during the last 2 h in both groups. The gas exchange improved with PEEP, arterial oxygen tension increased from 30.4 +/- 8.9 kPa to 38.6 +/- 2.5 kPa (P less than 0.01), and the shunt fraction decreased from 6.0 +/- 3.8% to 1.2 +/- 0.8% (P less than 0.001). There were significant differences (P less than 0.01) in both PaO2 and shunt fraction between the ZEEP and PEEP groups throughout the study. In conclusion, positive end-expiratory pressure improves gas exchange but does not protect against increasing extravascular lung water during the creation of hydrostatic pulmonary oedema. PMID- 1595336 TI - Effect of alpha-chloralose, halothane, pentobarbital and nitrous oxide anesthesia on metabolic coupling in somatosensory cortex of rat. AB - The effect of various anesthetics on the functional-metabolic coupling of cerebral cortex was studied in rats submitted to unilateral somatosensory stimulation. The regional cerebral metabolic rate of glucose (CMRglc) was measured autoradiographically using the 2-deoxyglucose method, and somatosensory activation was carried out by electrical stimulation of the left forepaw. In animals treated with 70% nitrous oxide, 0.5% halothane/70% nitrous oxide or 40 mg/kg pentobarbital, CMRglc of somatosensory cortex did not change despite generation of primary evoked cortical potentials. Anesthesia with 80 mg/kg alpha chloralose, in contrast, led to a focal increase of CMRglc in the primary somatosensory cortex from 52.1 +/- 18.3 to 73.1 +/- 18.9 mumol/100 g/min (means +/- s.d.). Metabolic activation was strictly confined to the forelimb (FL) area of somatosensory cortex, and it exhibited a laminar pattern with maximal activation in layers I, II and IV. The preservation of functional-metabolic coupling under a surgical dose of chloralose renders this anesthetic particularly suited for the investigation of coupling processes under conditions where the experimental requirements preclude the use of unanaesthetized animals. PMID- 1595338 TI - EDTA-dependent pseudothrombocytopenia in a preoperative patient. PMID- 1595337 TI - Application of sublingual buprenorphine in combination with naproxen or paracetamol for post-operative pain relief in cholecystectomy patients in a double-blind study. AB - In a double-blind, placebo-controlled study in 125 patients undergoing a cholecystectomy, a comparison was made of the quality of post-operative pain relief during 'patient-controlled' intake of sublingual buprenorphine in combination with either rectally administered naproxen 1000 mg/24 h, paracetamol 4000 mg/24 h or a placebo. Results obtained in 97 patients were analysed. Five of these patients needed a rescue medication with morphine hydrochloride intramuscularly because of insufficient pain relief or because of nausea and vomiting. The quality of pain relief, as measured on a four-point scale, was comparable in all three groups throughout the study period and no significant differences became apparent. Only on the day of surgery (day 0) was intake of buprenorphine significantly greater in the placebo group (2.3 tablets/24 h) than in the naproxen and paracetamol groups (1.8 and 1.5 tablets/24 h, respectively). It is concluded that after cholecystectomy 'patient-controlled' intake of sublingual buprenorphine as a sole agent provides acceptable pain relief in about 80% of patients. More elaborate methods, such as intravenous patient-controlled analgesia, might be necessary to achieve good pain relief in the remainder of these patients. PMID- 1595339 TI - Intrapulmonary thrombin generation and its relation to monomethylmethacrylate plasma levels during hip arthroplasty. AB - Frequent peroperative sampling of arterial and mixed venous blood was undertaken in eight consecutive patients during cemented hip arthroplasty to obtain a sequential picture of thrombin-antithrombin (TAT) and methylmethacrylate monomer (MMA) concentrations. TAT, detected neo-antigenically, reached its maximum levels after bone preparation, prior to introduction of cement and prosthesis. Furthermore, TAT values were higher in arterial than in mixed venous blood, indicating generation and inactivation of thrombin when blood is passing the lung. MMA concentration, measured by high pressure liquid chromatography, increased very rapidly and declined within 1 min following socket as well as shaft implantation, reaching the highest mean value of 3599 ng/ml only 30 s after femoral impaction of cement. MMA concentration was higher in mixed venous than in arterial blood, indicating elimination of the monomer during lung passage. This study confirms our previous observation that coagulation is activated prior to the implantation of bone cement and prosthesis into the femoral shaft; in addition, it provides further evidence of the thrombin-generating potential of the pulmonary capillary bed. Very frequent sampling was necessary to reveal the sharp rise in MMA levels following impaction of cement. Further investigations are needed to establish whether interaction between activated coagulation and MMA may predispose to cardiovascular complications. PMID- 1595340 TI - Characteristics of muscle nerve sympathetic activity during general anaesthesia in humans. AB - General anaesthesia influences the cardiovascular system at different levels. To increase our knowledge of how sympathetic outflow is affected by anaesthetic interventions, we used direct microelectrode recordings of muscle sympathetic activity (MSA) in the peroneal nerve in 18 patients scheduled for ENT-surgery. During induction of anaesthesia (propofol 2.1 mg/kg or methohexitone 1.4 mg/kg), all patients showed reductions in MSA (from 41 +/- 4 to 20 +/- 4 bursts/min). With endotracheal intubation there was a sudden increase of activity and in several patients the normal pulse-synchrony of MSA was lost temporarily. Maintenance of anaesthesia with nitrous oxide (n = 12) increased MSA and methohexitone (n = 2), propofol (n = 3) and isoflurane (n = 8) decreased MSA, while the effect of halothane (n = 3) varied. Baroreflex mechanisms were still operative but seemed to be depressed in relation to anaesthetic agent and depth. Laryngeal and surgical stimuli caused increases in MSA and blood pressure, lasting several minutes after the stimulation. It is concluded that the strength of MSA is profoundly influenced by the choice of anaesthetic agent. A suppression of activity is more common than an increase. Qualitatively, several sympathetic reflexes operate in a similar way during light anaesthesia as in awake subjects, but are depressed or absent during deep anaesthesia. PMID- 1595341 TI - The influence of changes in blood flow on the accuracy of pulse oximetry in humans. AB - Oxygen saturation (SpO2) was measured with a pulse oximeter in ten healthy, young men breathing air. A pulse oximeter probe was attached to the second toe and a laser Doppler probe to the first toe of the same foot for measurement of changes in peripheral blood flow. The pulse oximeter and laser Doppler readings were simultaneously compared when the foot was positioned 40 cm (position 1) above heart level, elevated 10 cm (position 2) above heart level and horizontally at heart level (position 3). Using this experimental human model, we achieved various blood flows. The AC and DC optical signals used for determination of oxygen saturation were recorded from the pulse oximeter and analysed. There was a significant increase (P less than 0.05) between position 1 and 3 in blood flow as measured by the laser Doppler flow meter. The corresponding pulse oximeter readings of haemoglobin saturation also increased significantly (P less than 0.05) comparing these two leg positions. Analysing the AC- and DC optical signals, the AC value of infrared light increased considerably, while the AC value of the red light decreased slightly. The DC values of red and infrared light did not change significantly. In summary, when blood flow was decreased, the ratio of red to infrared transmitted light was changed, resulting in a low SpO2 reading. PMID- 1595342 TI - Capsaicin pretreatment of rats does not prevent tissue extravasation of albumin from intra-abdominal trauma. AB - Intra-abdominal surgery causes a loss of plasma into tissues within and around the abdomen, predisposing to a decreased tissue viability and postoperative complications. In a rat model of intra-abdominal trauma, we investigated whether neuropeptides released from thin afferent nerve endings may contribute to this extravasation. Newborn male Wistar rats were pretreated with capsaicin 50 mg/kg s.c., leading to a lifelong degeneration of thin afferents. The same animals, when adult, were subjected to experiments under chloralose anesthesia in which tissue clearances of radiolabelled albumin were determined by a double isotope technique. Non-pretreated animals served as controls. In non-traumatized animals, pretreated rats had a higher loss of labelled albumin in calf muscle. In animals subjected to the standardized intra-abdominal trauma, the pretreatment did not decrease the trauma-induced loss of albumin. In neck skin, the loss of protein was higher in pretreated animals, possibly due to a decreased trauma-induced sympathetic activation. In conclusion, degeneration of thin afferent fibers may alter the autonomic reflex response to intra-abdominal trauma, but neuropeptide release from afferents apparently plays no role in the relocation of albumin. PMID- 1595343 TI - Does alfentanil preserve left ventricular pump function during rapid sequence induction of anaesthesia? AB - A double-blind, randomised trial was conducted in 24 patients without cardiopulmonary disorders (20-43 years), to assess the effect of an intravenous bolus of alfentanil on the circulatory and catecholamine responses to rapid sequence induction of general anaesthesia. Induction included injection of thiopentone 5 mg/kg and suxamethonium 1.5 mg/kg in rapid succession, followed by laryngoscopy and intubation. Half of the patients received alfentanil 100 micrograms/kg immediately before thiopentone. The other half received saline. Blood pressure, heart rate, and plasma catecholamine concentrations were measured repeatedly, together with left ventricular ejection fraction assessed by radionuclide angiocardiography. The responses following laryngoscopy and intubation were completely different in the saline vs. the alfentanil group: rate pressure product +76% vs. -32%, mean arterial blood pressure +46% vs. -25%, heart +46% vs. no change, noradrenaline +117% vs. -25%, adrenaline +50% vs. -53%, and left ventricular ejection fraction -32% vs. no change. In conclusion, during rapid sequence induction of anaesthesia with thiopentone and suxamethonium, an intravenous bolus of alfentanil 100 micrograms/kg 1 min before laryngoscopy and intubation completely prevents hypertension, tachycardia, decrease in left ventricular ejection fraction, and activation of plasma catecholamines, though at the expense of moderate hypotension. PMID- 1595344 TI - Complications and side effects during thiopentone therapy in patients with severe head injuries. AB - This study reports all complications and side effects occurring in 38 patients with severe traumatic brain lesions treated with barbiturate coma because of a dangerous increase in intracranial pressure. The treatment was induced by intravenous infusion of thiopentone (5-11 mg.kg-1) followed by a continuous infusion of 4-8 mg.kg-1.h-1. The subsequent rate of thiopentone infusion was governed by the level of the intracranial pressure with the intention of keeping ICP below 20 mmHg (2.7 kPa). The duration of treatment was 1-15 days. Arterial hypotension occurred in 58%, hypokalemia in 82%, respiratory complications in 76%, infections in 55%, hepatic dysfunction in 87% and renal dysfunction in 47% of the patients. Twenty patients survived. Mortality in 17 patients was caused by an untreatable increase in intracranial pressure. In one patient complications due to barbiturate treatment may have contributed to the fatal outcome. In none of the other cases were the noted complications and side effects associated with any permanent symptoms or dysfunctions. PMID- 1595345 TI - Effect of thoracic epidural etidocaine 1.5% on somatosensory evoked potentials, cortisol and glucose during cholecystectomy. AB - The effect of thoracic (T7-8) epidural etidocaine 1.5%, 9 ml, and continuous per- and postoperative epidural infusion of etidocaine 1.5%, 4 ml/h, on early (less than 500 ms) somatosensory evoked potentials (SEPs), and cortisol and glucose in plasma during cholecystectomy, was examined in ten patients. Spread of analgesia (pin-prick) was T3 (T1-T3) to L2 (T11-L3) 35 min after injection of etidocaine, and T3 (T2-T4) to T12 (T8-L4) 3 h after surgical incision (median (range)). Before operation, epidural etidocaine had no significant effects on peak-to-peak amplitude of SEPs to electrical stimulation at the L1, T10 or T6 dermatomal level (P greater than 0.09). SEPs were abolished in only two patients at T6, and no patient had SEPs abolished at T10 or L1. The plasma concentrations of cortisol and glucose were significantly increased 20 min after surgical incision and remained increased throughout the study. No correlation was found between the block-induced decrease in the peak-to-peak amplitude at T6 or T10 and increase in plasma cortisol, except for a negative correlation at T10 and the initial increase in cortisol (Rs = 0.72, P = 0.03). In conclusion, thoracic epidural administration of 9 ml of etidocaine 1.5% does not provide total afferent somatic blockade assessed by SEP and the stress response to cholecystectomy. PMID- 1595346 TI - Respective effects of malnutrition and phosphate depletion on endurance swimming and muscle metabolism in rats. AB - To examine the respective roles of malnutrition and phosphate depletion on muscle exercise capacity and bioenergetics, phosphate-depleted, either underfed or partly refed rats; phosphate-supplemented, either underfed or partly refed rats; and well-nourished control animals were studied, using swim time to exhaustion and 31P NMR spectroscopy measurements of muscle phosphocreatine, inorganic phosphate, adenosine triphosphate and intracellular pH. Only partly refed rats displayed hypophosphataemia. Swim time to exhaustion was lower in non-refed rats than in controls. Among the four groups, both refeeding and phosphate depletion positively affected swim time to exhaustion (both with P less than 0.02), and swim time to exhaustion was negatively correlated with phosphataemia (P less than 0.05). At rest, the ratio of muscle phosphocreatine/inorganic phosphate was lower in the phosphate-supplemented rats than in controls, whereas muscle phosphocreatine/adenosine triphosphate and intracellular pH were comparable. After non-tetanic stimulation, the muscle phosphocreatine recovery was slower in the four groups than in controls and closely correlated with exhaustion (P less than 0.01). These findings suggest that malnutrition alters the capacity of muscular work, mainly because of a reduced cell oxidative energy availability. These patterns are improved by partial refeeding and clearly influenced by the level of phosphorus intake, whether depletion is capable of improving metabolic alterations or uncontrolled supplementation is deleterious in malnourished animals. PMID- 1595347 TI - Neutrophil influx into guinea-pig airway lumen during cholinergic and non cholinergic bronchoconstriction. AB - Sensory nerve activation will produce adherence of neutrophils to tracheobronchial microvessels. The aim of the present study was to investigate whether this adherence would lead to an influx of neutrophils into the airway lumen. To do this, we studied the effects of 20 minutes of vagal stimulation (1 Hz, 5 ms, 5 V) in anaesthetized and tracheostomized guinea-pigs on both lung resistance, and the cell picture in bronchoalveolar lavage. Any changes were compared to those of intravenous methacholine infusion, producing similar changes in lung resistance. Since high pressure ventilation could produce lung damage, we also studied the effects of ventilation through an extracorporeal resistor, producing a similar change in transpulmonary pressure (45 +/- 2 cmH2O) as vagal stimulation (42 +/- 4 cmH2O). The total number of cells recovered in the lavage was not increased by vagal stimulation, methacholine infusion or the extracorporeal resistor. However, both vagal stimulation and methacholine infusion significantly increased the relative number of neutrophils in the lavage compared to sham stimulated animals (21 +/- 11%, 13 +/- 4% and 4 +/- 1% respectively), but the extracorporeal resistor had no effect (4 +/- 2%). Our data suggests that prolonged bronchoconstriction per se may induce an influx of neutrophils into the airway lumen of the guinea-pig. PMID- 1595348 TI - Inhibition of the arginine/nitric oxide pathway causes bladder hyperactivity in the rat. PMID- 1595349 TI - Energy metabolism in type I and type II human muscle fibres during short term electrical stimulation at different frequencies. AB - The degradation of adenosine triphosphate, phosphocreatine and glycogen was determined in type I and type II fibres of the human quadriceps femoris muscle during intermittent electrical stimulation at 20 and 50 Hz, (1.6 seconds stimulation, 1.6 seconds rest). Seven healthy volunteers took part in the study. Muscle biopsy samples were obtained at rest and after 10 and 20 seconds of stimulation (six and 12 contractions, respectively). The resting contents of adenosine triphosphate, phosphocreatine and glycogen were all higher (P less than 0.05) in type II fibres compared to type I fibres. By the end of stimulation, whole muscle force production had declined to 84 and 77% of the initial force at 20 and 50 Hz, respectively. The phosphocreatine degradation rate for 10 and 20 seconds of stimulation was greater in type II fibres (P less than 0.05) compared to type I fibers at both 20 and 50 Hz. The rates of glycogenolysis after 20 seconds stimulation in type II fibres were 3.18 +/- 1.1 and 6.31 +/- 1.39 mmol glycosyl units kg-1 s-1. The corresponding rates in type I fibres were 0.46 +/- 0.73 and 0.60 +/- 0.39 mmol glycosyl units kg-1 s-1, which were not significantly different from zero. It is hypothesized that the decline in whole muscle force observed during electrical stimulation may be a consequence of the rapid loss of PCr stores in type II fibres. PMID- 1595350 TI - Effects of detraining following short term resistance training on eccentric and concentric muscle strength. AB - Healthy males were examined before and after 12 weeks of accommodated resistance training (three week-1) and after 12 weeks of detraining. Training consisted of four to five sets of six coupled maximum voluntary bilateral concentric and eccentric (Grp ECCON; n = 10) or 12 concentric (Grp CON; n = 8) quadriceps muscle actions. Concentric and eccentric peak torque at various constant angular velocities and three repetition maximum half-squat and vertical jump height were measured. Grp ECCON showed greater (P less than 0.05) overall increase in peak torque after training and detraining than Grp CON. Thus, concentric peak torque (0.52 rad s-1) increased more (P less than 0.05) over the experimental period in Grp ECCON and increases in eccentric peak torque were preserved in Grp ECCON only. Increases in peak torque in response to training were greater (P less than 0.05) at 0.52 than at 2.62 rad s-1. Alterations in the torque-velocity patterns induced by training remained after detraining in Grp ECCON but not in Grp CON. The retained increases (P less than 0.05) in half-squat were 12 and 18% in Grps CON and ECCON, respectively. Neither group showed increased vertical jump height after detraining. This study showed greater preservation of concentric and eccentric peak torque after detraining following coupled concentric and eccentric than concentric resistance training. Only the former regime induced a change in the shape of torque-velocity curves that was manifest after detraining.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595351 TI - Effect of prior exercise in Pi/PC ratio and intracellular pH during a standardized exercise. A study on human muscle using [31P]NMR. AB - Seven subjects underwent a standard localized exercise of calf muscles in order to investigate whether the metabolic exercise-induced steady-state, as revealed by the evaluation of inorganic phosphate/phosphocreatine ratio, depends on the conditioning of the muscle just prior to the exercise. The experimental protocols consisted of two separate experiments using first [31P]nuclear magnetic resonance spectroscopy and second (on 3 subjects) infrared oxyphotometry to respectively follow variation of energy metabolism and tissular deoxygenation. The exercise consisted of 240 successive plantar flexions (0.5 Hz frequency) against a high load equivalent to 80% of the maximal voluntary contraction. This exercise was accomplished before cold exercise and after warm exercise, a warming-up period bringing to approximately 50% of VO2max. The results showed that: (1) steady state level of phosphate/phosphocreatine and intracellular acidosis was significantly lowered by warming-up; (2) cold and warm exercise steady-state of calculated adenosine diphosphate values were not significantly different; (3) cold exercise rapidly induced a high tissular deoxygenation that is not observed during warm exercise; and (4) time-constant of phosphocreatine resynthesis is lowered after warm exercise but the initial slope of time-evolution is not modified. Parallel experiments also showed that phosphate/phosphocreatine steady state was not modified in comparison with warm exercise when the same power of exercise was reached by stepwise incrementation of the charge. From these results we postulate that a better tissue oxygenation due to a global or localized warming-up allows to reach the same mechanical performance with a lower decrease of PCr content, owing to a faster adjustment of oxidative metabolism during the transitional period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595352 TI - Myocardial lactate extraction and release at rest and during heavy exercise in healthy men. AB - The relationship between myocardial lactate extraction and blood lactate concentration and the possibility that simultaneous uptake and release of lactate occur in the normal human heart was investigated by measuring arterial-coronary sinus differences of lactate and of labelled lactate during infusion of 14C lactate in 13 healthy young male volunteers. Measurements were done at rest, during increased cardiac work with unaltered arterial lactate concentration achieved by atrial pacing and during increased cardiac work and increased arterial lactate concentration achieved by supine cycle ergometer exercise. There was on no occasion a significant difference in 14C lactate specific activity between arterial and coronary sinus blood, i.e. no significant admixture of non labelled lactate occurred in the coronary sinus indicating that on no occasion was there any sign of lactate release. The myocardial extraction of lactate seemed to be a linear function of arterial lactate concentration. During exercise with an arterial lactate concentration of 6 mmol l-1 and above, lactate could have covered approximately 75-100% of the oxidative metabolism. Thus, during short-term heavy work myocardial lactate extraction dominates over other substrates (mainly free fatty acids and glucose) taken up by the heart, and used for oxidation by the heart muscle cells. PMID- 1595353 TI - Acute effect of hypobaria and hypoxia on renal nerve activity in anaesthetized rabbits. AB - To determine the acute effect of reduced barometric pressure and hypoxia on renal nerve activity, urethane-anaesthetized and mechanically ventilated rabbits were randomly exposed to the following four separate conditions in a decompression chamber: hypoxic hypobaria (n = 7), hypoxic normobaria (n = 5), normoxic hypobaria (n = 8) and slow normoxic hypobaria (n = 7). A combination of rapid decompression and simultaneous adjustment of inspired PO2 was used to simulate an altitude of 6600 m, and renal nerve activity and haemodynamics, such as systemic blood pressure and heart rate, were measured. During both hypoxic hypobaria and hypoxic normobaria, there were significant and similar increases in renal nerve activity at 6600 m (54 +/- 7% and 61 +/- 13% from each baseline, respectively). However, there were no changes in renal nerve activity during normoxic hypobaria or slow normoxic hypobaria with decompression rates of 1000 or 400 m min-1, respectively. From these results, we conclude that a reduction in barometric pressure without hypoxia does not affect renal nerve activity in anaesthetized rabbits. PMID- 1595354 TI - An isolated perfused rat kidney preparation designed for assessment of glomerular permeability characteristics. AB - The aim of the present investigation was to modify the widely used isolated perfused rat kidney preparation to make it more suitable for studies of glomerular permeability to macromolecules. Both kidneys were perfused in situ using separate pumps in two of each other independent systems with Tyrode solution containing human serum albumin (18.2 g l-1). Sodium nitroprusside was administered to induce dilatation and to maintain constant vascular resistance (PRU100) during the experiments. The addition of sodium nitroprusside decreased vascular resistance from 0.17 +/- 0.05 to 0.09 +/- 0.02 mmHg min-1 100 g-1 ml-1 and increased urine flow and glomerular filtration rate. The temperature of the perfusate was reduced from 37 degrees C to 8 degrees C to inhibit tubular reabsorption of protein and fluid, resulting in a urine to plasma concentration ratio of [51Cr]EDTA of 1.26 +/- 0.07. Furosemide reduced the urine to plasma concentration ratio for [51Cr]EDTA further to 1.15 +/- 0.02 and increased glomerular filtration rate. Moreover, by performing the studies at low temperatures (8 degrees C) in the presence of sodium nitroprusside and furosemide it was possible to achieve low and stable albumin fractional clearance values close to those prevailing in vivo. Thus, the described technique, allowing simultaneous perfusions of both kidneys with different solutions, pressures and flows, seem to be well suited for studies of macromolecular transport across glomerular capillaries. PMID- 1595355 TI - Intracerebroventricular immunization with TRH-antiserum lowers blood pressure in spontaneously hypertensive rats. AB - Centrally administered thyrotropin-releasing hormone exerts a well documented hypertensive effect. In this study, the possible physiological role of thyrotropin-releasing hormone in the central cardiovascular regulation was evaluated in spontaneously hypertensive rats receiving long-term (8-14 days) intracerebroventricular infusion of a heterologous antiserum to thyrotropin releasing hormone. The effect of this passive immunization on the blood pressure was monitored from conscious animals by the tail-cuff method. Thyrotropin releasing hormone antiserum significantly decreased the systolic arterial pressure in adult rats with established hypertension. No alterations in serum thyroid hormone status were observed indicating that the antihypertensive effect of immunological blockade of thyrotropin-releasing hormone was not due to changes in the serum thyroid hormone levels. These results provide evidence for a role of endogenous brain thyrotropin-releasing hormone in the maintenance of hypertension in spontaneously hypertensive rats. PMID- 1595356 TI - Reversal by concanavalin A of the inhibitory effects of extracellular Ca2+ on pinocytosis in Amoeba proteus. AB - When Concanavalin A, 1-20 micrograms ml-1 binds to the surface of Amoeba proteus the cell's response to Ca2+ and to cationic inducers of pinocytosis is strikingly altered. Separately, Concanavalin A and Ca2+ are weak inducers but their combined effects are intense pinocytosis and suppression of the normal inhibitory effect of Ca2+ on cation-induced pinocytosis. At high concentrations (greater than 25 micrograms ml-1) the lectin increases cellular uptake and binding of 45Ca in the cell surface but the ionic permeability and the potential of the cell membrane are little changed by treatment with Concanavalin A. Subsequent addition of Ca2+ starts the pinocytic cycle and causes a fivefold increase of the membrane resistance without depolarizing the cell. Neither a rise of free intracellular calcium nor an influx of 45Ca precedes formation of pinocytotic channels when Con A is applied to cells in the presence of calcium. All effects of Concanavalin A are blocked by alpha-methylmannoside while succinyl-Concanavalin A is without effects on pinocytosis. These findings suggest that crosslinking of cell surface carbohydrates reverses calcium inhibition of pinocytosis and increases the cell's pinocytotic response to cations without modifying either the bioelectrical effects or the intracellular free concentration of calcium. PMID- 1595357 TI - Effect of arm-cranking on leg blood flow and noradrenaline spillover during leg exercise in man. AB - Controversy exists whether recruitment of a large muscle mass in dynamic exercise may outstrip the pumping capacity of the heart and require neurogenic vasoconstriction in exercising muscle to prevent a fall in arterial blood pressure. To elucidate this question, seven healthy young men cycled for 70 minutes at a work load of 55-60% VO2max. At 30 to 50 minutes, arm cranking was added and total work load increased to (mean +/- SE) 82 +/- 4% of VO2max. During leg exercise, leg blood flow average 6.15 +/- .511 minutes-1, mean arterial blood pressure 137 +/- 4 mmHg and leg conductance 42.3 +/- 2.2 ml minutes-1 mmHg-1. When arm cranking was added to leg cycling, leg blood flow did not change significantly, mean arterial blood pressure increased transiently to 147 +/- 5 mmHg and leg vascular conductance decreased transiently to 33.5 +/- 3.1 ml minutes-1 mmHg-1. Furthermore, arm cranking doubled leg noradrenaline spillover. When arm cranking was discontinued and leg cycling continued, leg blood flow was unchanged but mean arterial blood pressure decreased to values significantly below those measured in the first leg exercise period. Furthermore, leg vascular conductance increased transiently, and noradrenaline spillover decreased towards values measured during the first leg exercise period. It is concluded that addition of arm cranking to leg cycling increases leg noradrenaline spillover and decreases leg vascular conductance but leg blood flow remains unchanged because of a simultaneous increase in mean arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595358 TI - An epidemiological study of mental health and socioeconomic conditions in Sumatera, Indonesia. AB - A mental health survey was conducted in Palembang, Indonesia, to test the hypothesis that rapid socioeconomic and cultural change is detrimental to mental health. The 30-item General Health Questionnaire, translated into Bahasa Indonesia, was administered to a probability sample of 1670 adults (94.9% of the target sample). The Present State Examination was conducted on a weighted subsample of 100, using a 2-phase design. Overall morbidity rates were surprisingly similar to those in industrialized countries. A strong association was found between psychological symptoms and poverty. Persons belonging to communities that had progressed substantially in standards of living had fewer symptoms. The evidence points to a possibly beneficial effect of economic progress on mental health. Longitudinal data are needed to confirm this. PMID- 1595359 TI - The St. George's dementia bed investigation study: a comparison of clinical and pathological diagnosis. AB - Sixty-four elderly patients who had been admitted to the St. George's Hospital Alzheimer's disease evaluation project during 1981-1989 were followed up to postmortem examination. Comparison between clinical diagnoses and neuropathological diagnoses indicated positive predictive values for the antemortem diagnoses of 50-67%. Existing clinical criteria may not be accurate enough to permit firm antemortem diagnosis of older people for either research or clinical purposes. PMID- 1595361 TI - Drop-out rate as a performance indicator in psychotherapy. AB - Many large studies of psychotherapy show that the median patient drops out by the 5th session and most before the 10th session. Data from an effective behavior therapy clinic for the anxiety disorders showed that only 17% of patients failed to complete a median of 60 h of therapy. Patient characteristics were not associated with attrition. We examined 5 meta-analytic treatment reviews and found the median drop-out rate was 8% after 20 h of therapy. We suggest that low attrition is associated with effective, standardized treatment and as such, drop out rate may be a proxy variable that can indicate effective service delivery. PMID- 1595360 TI - Hypothalamic-pituitary-adrenocortical function in mixed and pure mania. AB - There is little information about hypothalamic-pituitary-adrenocortical (HPA) axis function in mania, particularly in mixed states. We therefore investigated HPA function and its relationship to clinical state in 19 hospitalized manic patients meeting Schedule for Affective Disorders and Schizophrenia - Research Diagnostic Criteria for acute manic episodes, compared patients with and without a mixed presentation, and examined correlations between HPA activity and behavior. Data were available from 13-16 patients. Behavioral and biochemical analyses were conducted during a 15-d placebo period. Patients with mania had elevated cerebrospinal fluid (CSF) and urinary free cortisol excretion compared with healthy subjects, and did not differ from depressed patients in any cortisol measures. Mixed manics had significantly higher morning plasma cortisol, postdexamethasone plasma cortisol and CSF cortisol than pure manics. Five of 7 mixed manics and 3 of 9 pure manics were dexamethasone suppression test (DST) nonsuppressors. Afternoon plasma cortisol and CSF cortisol correlated significantly with depressed mood; urinary free cortisol correlated with anxiety. None of the cortisol measures correlated with mania or agitation scores. These data suggest that increased cortisol secretion is a characteristic of the depressed state in mixed manics, although pure manics may also have increased DST nonsuppression. PMID- 1595362 TI - The structure of personality disorders in DSM-III. AB - In DSM-III it is proposed that there are 11 personality disorders (PDs) that fall into 3 superordinate clusters: cluster A, labelled the odd or eccentric; cluster B, labelled the emotional, dramatic or erratic; and cluster C, described as the anxious or fearful. To check this proposal, data were obtained from a sample of 112 state hospital psychiatric inpatients via the Structured Interview for DSM III Personality (SIDP). Various statistical techniques were applied to the data, ranging from the least constrained method of multidimensional scaling to the most constrained and statistically rigorous approach of confirmatory factor analysis. In the latter approach, the models suggested by the various statistical approaches were contrasted directly. A 3-cluster solution was accepted as the best representation of the data, although PD membership of the 3 clusters varied in some ways from those suggested by DSM-III. An exploratory correlation analysis showed that many of the items were more strongly correlated with PDs other than the ones specified by DSM-III, but generally items clustered within the 3 superordinate clusters. This issue deserves further investigation. PMID- 1595363 TI - Attempted suicide and depression in schizophrenia. AB - The relationships between symptoms and both prior suicide attempts and current suicidal thinking were examined in a sample of schizophrenics at 2 points in time. Fifty subjects meeting DSM-III criteria for schizophrenia were assessed within 1 week of admission, and 41 were reassessed at a 6-month follow-up. On admission, prior suicide attempts were significantly associated with current depression, female sex, lower education and more frequent hospitalization. The association with depression remained significant at follow-up. In addition, current suicidal thinking was associated with depression at both times but also with negative symptoms at time 1 and delusions and hallucinations at time 2. These findings confirm and strengthen prior reports of an association between depression and attempted suicide. PMID- 1595364 TI - Treatment resistance of depression after head injury: a preliminary study of amitriptyline response. AB - Thirteen patients with depression following minor head injury were matched with 13 functional depressives. Both groups were indistinguishable psychopathologically. Five of the functional group had a family history of affective disorder and none of the head-injury group had such a history. Both groups were treated with amitriptyline, beginning with 100 mg daily, increasing to a maximum of 250 mg/d. There were significant differences in response between the 2 groups, with only 4 of the head-injury patients improving. Our preliminary results suggest that this condition is relatively resistant to tricyclic therapy. PMID- 1595365 TI - Early signs of cognitive deficits among human immunodeficiency virus-positive hemophiliacs. AB - A total of 181 human immunodeficiency virus (HIV)-seropositive hemophiliacs and 28 hemophilic controls were evaluated by psychometric tests and by electroencephalogram (EEG). Patients were classified from stages 1-6 according to the immunological criteria of the Walter Reed staging system. Statistical analysis of psychometric data showed an effect of the stage of the disease on test performances, indicating a decline in attention, accumulation of perceptual interferences, decline in visuoperceptual speed and visuomotor response speed and reduced verbal memory performance, especially in stage 6 patients. Comparison of performance levels with normative test data already revealed cognitive deficits in about 20-30% of the patients in stages 2-5. As regards verbal memory, especially learning and recognition of new verbal information were impaired. In contrast, there was no significant deficit for nonverbal memory processing. Compared with the controls, patients exhibited an increasing number of abnormal EEG findings in stages 2-6. As a conclusion, in the stages before acquired immunodeficiency syndrome (AIDS) develops, EEG findings as well as psychometric findings indicate central nervous system involvement of AIDS in about 20-30% of cases, whereas in full-blown AIDS there is a marked increase to 80%. Besides a more general deficit of attention and psychomotor speed as is seen in subcortical dementia, there is evidence for a particular verbal learning disorder, suggesting additional selective impairment of the brain. PMID- 1595366 TI - [Renal cell carcinoma and Reiter's syndrome]. AB - A case of a prolonged febrile syndrome in a 41-year old man is presented. A renal tumor and a seronegative spondylitis associated with a Reiter's syndrome were disclosed together. The authors did not find any reference to an eventual relation between these two diseases. PMID- 1595368 TI - [The new biomedical and health research program of the European Economic Community--BIOMED 1 (1990-94)]. AB - The new EEC Biomedical and Health Research Programme (BIOMED 1) is presented. After a brief introduction on the background of the Programme--in which an overview of the ongoing Medical and Health Research Programme (MHR 4) is given- the main features of the new Programme are pointed out. On what concerns its aims and objectives, concertation and coordination of national research programmes at community level are stressed as well as the need to apply to the maximum possible extent the principles of subsidiary and community added value, in order to ensure an European dimension to the actions which are going to be supported and to achieve the harmonization of research methodologies, procedures and data. As regards the content of the Programme a description is made of its four main areas: Area 1--Development of co-ordinated research on prevention, care and health systems (main topics: drugs and the administration of medicines; risk factors and occupational health; biomedical technology; health services research); Area 2--Major health problems and diseases of great socio-economic impact (AIDS; cancer; cardiovascular disease; mental illness and neurological disease; the ageing process, and age-related health problems and handicaps); Area 3--Human Genoma Analysis (improvement of the genetic map; physical mapping; DNA sequencing; data-handling and databases; technology development and applications of human genome analysis); Area 4--Research on biomedical ethics (compilation of legislation; evaluation of questions of biomedical ethics linked with the Programme; evaluation of the social impact of the Programme and its risks).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595367 TI - [Hyperthyroidism caused by non-neoplastic inappropriate TSH secretion]. AB - We report a case of hyperthyroidism due to non-neoplastic inappropriate thyrotrophin secretion in a 31 year old woman. Increased T3 and THS levels after thyroidectomy led us to suspect the diagnose. Serum levels were further increased by TRH and only partially suppressed by triiodothyronine and computerised axial tomography showed a normal sellar region. These features are characteristic of inappropriate TSH secretion due to thyrotroph resistance to thyroid hormones. Bromocriptine and octreotide were ineffective in lowering TSH levels. Pregnancy and breastfeeding postponed 3,5,3'-triiodothyroacetic acid therapy. PMID- 1595369 TI - [Stapling in surgery of cancer of the rectum. Experience with 100 cases]. AB - The authors relate their experience with 100 cases of anterior resections operated using stapling techniques, 43 with double stapling. Fifty three were males and forty seven females, the youngest being 35 year's old and the oldest 87. The tumour was located at the upper third in 54 cases, at the middle third in 41 and at the lower third in five cases. One hundred anterior resections were executed, fifty of the low type. As to the Dukes classification, 15 were A type, 45 type B, 35 type C and 5 type D. There were no operative mortality until the 30th post operative day. As early post-operative complications there were one case of hemorrhage, two pneumopathies, one urinary retention, one cardio respiratory insufficiency three cases of fistulae and 6 wound infections. In the last 65 cases only one wound infection and two pneumopathies were found. As late complications there were three anastomotic stenosis (all of them satisfactorily solved with dilatation) and six cases with small degree incontinence for gas and faeces recovering spontaneously. The recurrence rate was 14%; in three it has been possible to proceed with its excision by means of abdominoperineal amputation. They conclude stating that mechanical suturing specially is a good alternative to manual suturing in patients with low rectal tumours. PMID- 1595370 TI - [Significance of digestive hemorrhage in patients with chronic renal insufficiency in hemodialysis]. AB - Gastrointestinal Bleeding (GIB) is a complication in patients with Chronic Renal Failure (CRF) on regular hemodialysis (HD). To analyse the importance of GIB we studied, retrospectively, the causes of hospitalization in 301 patients, all on HD in the same Unit in January 1990. The average age was 57.4 +/- 14.2 years (17 to 87), time on HD 58.3 +/- 44.9 months, male = 166, female = 135. Of a total of 169 hospitalizations, the infectious disease were the most frequent cause with 37 admissions (21.9%), followed by gastrointestinal diseases with 34 admissions (21.1%). Of these, 23 (13.6%) were due to GIB (Upper GIB = 19, Lower GIB = 4). The etiologies of Upper GIB were: Peptic Ulcer = 9, erosive Gastritis/Duodenitis = 7. Angiodysplasia = 1, Mallory Weiss = 1 and unknown = 1. The etiologies of Lower GIB were: Angiodysplasia of the colon = 3, Cancer of the colon = 1. Non steroid anti-inflammatory drugs (NSAID) had a positive correlation (p less than 0.01) with Upper GIB due to erosive Gastritis/Duodenitis. Surgery was necessary in a 8 cases of GIB, 7 of them due to Peptic Ulcer. GIB is an important cause of morbidity in patients with CRF on HD. Peptic Ulcer and erosive Gastritis/Duodenitis were the most frequent causes of GIB in the population studied. Angiodysplasia of the colon was the most important cause of Lower GIB. NSAID appear to be a risk factor for GIB from erosive Gastritis and or Duodenitis. PMID- 1595371 TI - [Severity evaluation of ventilated patients at a respiratory intensive care unit with the APACHE II system]. AB - APACHE II system, is a simple and inexpensive method to evaluate severity of Intensive Care Patients. In a 2 years period (between 1988 and 1990), grading severity using APACHE II system, was performed on 498 consecutive mechanical Ventilated Patients in a Respiratory Intensive Care Unit. APACHE II was higher in COPD patients, but patients with Pneumonia and Organophosphate Poisoning had higher mortality. Correlating the different components of APACHE II with the results, we verified that Prognosis was not influenced by the Previous Health Status. Mortality was higher with increasing age, in patients with COPD and Organophosphate Poisoning. APS was the most important index for prognosis. Patients with Pneumonia and Organophosphate Poisoning had the highest APS. The Authors conclude that APACHE II is an objective and not time consuming method to evaluate severity in ICU Patients. However indexes measured on the first 24 hours of ICU staying are a result of severity of illness, treatment performed and time elapsed before ICU admission, and, this may be a possible source of bias when comparing different Unit results. PMID- 1595373 TI - [Aging and free radicals]. AB - Several theories on aging are presented. All of them give important contributions but none explains all the aspects of the problem. Oxygen radicals produced during cellular combustion contribute to aging through multiple cumulative microlesions throughout life. The importance of glucose is emphasized; it forms early and late Maillard compounds. Other causes of aging are discussed. PMID- 1595372 TI - [Methods for preserving bone marrow for autologous transplantation]. AB - For Autologous Bone Marrow Transplantation (ABMT) the patient's own marrow is harvested before myelotoxic high-dose radio-chemotherapy and later returned to promote hemopoietic reconstitution. Between harvest and return the bone marrow must be preserved. The time elapsed between harvest and return depends on the intended therapy. Although--bone marrow may keep its hematopoietic potential for a few days without freezing, preservation for longer periods imposes the need for cryopreservation. Some of the current methods for marrow preservation are reviewed, with special emphasis given to cryopreservation. Hospital de Santa Maria Bone Marrow Transplant Unit cryopreservation method is described. PMID- 1595375 TI - [Autologous transplantation of bone marrow]. PMID- 1595374 TI - [Brain aging and dementia]. AB - It is common knowledge that the base of the demographic pyramide is turning upwards as a consequence of the constant growing of the elderly population. This phenomenon worries everybody from families to government agencies. As a consequence, neuroscientists have been asked to cooperate for a better understanding of the problem related with the aging of the nervous system. Essentially they try to better grasp the mechanism of aging and their deleterious effects on the brain and how to fight the diseases of the nervous system with particular affinity for the aged people. We know that brain goes through morphological and biochemical changes with the passing of the years; it loses weight, microscopic changes occur and the activity of many neurotransmitters diminishes. In this context it is strange that some people still argue against the enfeeblement of the mental faculties with aging. Of all diseases of the nervous system tormenting the aged, the most common are depression and dementia. Most cases of depression and some forms of dementia are treatable but Alzheimer's disease, which afflicts a considerable percentage of old people, leading to greater psychological decline and leaving doctors helpless to halt it's unavoidable progress, is certainly the most dreaded old age mental sickness. The etiology of Alzheimer's disease is unknown. Under these circumstances several possibilities are investigated: genetic, infectious and toxic. Lately, investigators have focused their attention on amyloid, constitutive substance of the senile plaques one of the characteristic structural changes of the diseased brain. Nowadays there are studies on the relation between amyloid and a protein considered to be its precursor which has been found outside the nervous system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595376 TI - [Dermal nerve sheath myxoma. (Neurothekeoma)]. AB - A 59-year-old male presented with a painful nodule on the interscapular area of 20 year duration. The microscopic examination showed a myxomatous lobulated tumor composed of dendritic fusiform cells with some epithelioid and multinucleated cells typical of a nerve sheath myxoma. Immunohistochemical analysis demonstrated reactivity for S100 protein. Neither factor XIIIa nor epithelial membrane antigen (EMA) expression was found in the tumor cells. These findings suggest a schwannian origin for this tumor. PMID- 1595377 TI - [Poisoning at a polyvalent intensive care unit]. AB - A retrospective analysis was made concerning 1340 admissions to a multidisciplinary Intensive Care Unit over four years (1986-1989), because of acute poisoning. In 666 patients occurred 735 drug overdoses and in 674 patients, 691 non-drug intoxications. The drugs with main action in central nervous system were the most frequent in drug overdoses and the organophosphates insecticides in the non-drug intoxications. During the considered period there was an absolute and relative fall in the number of admissions for acute poisoning (480 vs 244, 15.1% vs 9.9%). The patients admitted were 698 men (289 in drug-overdoses and 409 in non-drug group) with a statistically significant difference between the type of intoxication and sex (p less than 0.001). Age mean was 40.2 +/- 19.6 years, almost the same in the two groups of intoxications. The peak incidence occurred from March to October. From the hospital area of Lisbon came 814 patients and outside of Lisbon 495 patients. The mean duration of stay in the ICU was 3.90 +2- 6.15 days, being 2.71 +/- 3.80 in the drug overdoses and 5.08 +/- 7.62 in non drug intoxications (p less than 0.001). From the therapeutic measures we emphasize mechanical ventilation (29.5%), total parenteral nutrition (18.5%), dialysis (2.9%), Swan-Ganz catheter (2.8%) and pacemaker (1.2%). The mortality rate was 13.7%, higher in non-drug intoxications (23.0%) than in drug overdoses (4.4%) (p less than 0.0001). PMID- 1595378 TI - [Determination of HBSAg in pregnancy. Epidemiologic study of 100 cases]. AB - There are some arguments concerning prenatal Hepatitis B testing: universal screening versus testing of risk groups. A thousand parturients were evaluated in order to assess the sensitivity of risk factors in the identification of Hepatitis B surface antigen (HBsAg) positive women. To achieve that purpose they were questioned regarding risk factors and blood samples were collected for HBsAg testing. Thirty two HBsAg positive parturients were identified. A larger number of HBsAg positive was found amongst women included in the class 5 of the Graffard scale (p = 0.005), or referring contact with patients with hepatitis (p = 0.01). These risk factors identified no more than 17 of the 32 positive mothers (sensitivity = 53%). None of the other risk factors proved significant. The entire questionnaire allows a sensitivity of 87.5% but presents a specificity of 22.5%. In this population, risk factors are not a good method of screening HBsAg positive women. A universal screening must be undertaken in order to prevent vertical transmission of the virus and to detect families in risk. PMID- 1595379 TI - [Urinary calcium, magnesium and uric acid in normal children]. AB - In a group of 327 normal children, aged 4 to 11, we measured Calcium (Ca) and Creatinine (Cr) in the second morning urine. In 226 of them, Magnesium (Mg) and Uric Acid (UA) were also calculated. Means and SD were respectively Ca/Cr: 0.11 +/- 0.09, Mg/Cr: 0.10 +/- 0.03, Mg/Ca: 1.56 +/- 1.48 and UA/Cr: 0.093 +/- 0.29. Distribution was not normal, so we used the 97.5 centile for the upper acceptable limit. This value was higher for Ca/Cr (0.37) and different for Mg/Cr (0.17), compared to the previous reports. Our values of Mg/Ca were related to age (p less than 0.01). These results suggest the need for local establishment of normal ranges and a better definition of hypercalciuria and hypermagnesiuria. PMID- 1595380 TI - [National screening for phenylketonuria, congenital hypothyroidism and congenital adrenal hyperplasia]. AB - In Portugal the screening for phenylketonuria (PKU) and congenital hypothyroidism (CH) was begun towards the end of 1979, and by 1990 59 cases of PKU and 227 cases of CH had been detected. The early initiation of treatment and the observed mental and motor development, point towards a normal development in these children. A trial screen for congenital adrenal hyperplasia was carried out in 100.000 newborns, from which it was concluded that, under the present conditions, screening at a national level is not justified. A similar study is currently being undertaken for biotinidase deficiency and cystic fibrosis. The results ares discussed, as are the cost/benefits evaluations. PMID- 1595381 TI - Pulmonar vascular changes in the plain chest film of cardiac patients. AB - The correct interpretation of chest film on cardiac patients is very important. The most important feature is the radiographic appearance of the pulmonary vascularity. Four different patterns of pulmonary vascularity are considered: normal, decreased, increased and uneven. The different diseases associated with each type are mentioned. From the pulmonary vascular pattern one can deduct hemodynamic data which are important for the diagnosis, grade of severity and follow-up. PMID- 1595382 TI - [Ethical and social issues on the human genome analysis]. AB - The modern technologies for human genome analysis raise a variety of ethical and social questions. The pre-symptomatic diagnostic of diseases of late expression is becoming possible for a rapidly increasing number of situations. The use of that knowledge by employers, insurance companies, schools, and society in general, could lead to discriminations and stigmatizations, in addition to adverse psychological reactions. DNA fingerprinting raises questions of privacy and personal autonomy in its applications to paternity proof, criminal proceedings, and establishment of data banks. The project of the immediate and complete sequencing of the human genome will lead to questions of economical ethics, as well as of access, commercialization and property rights of scientific information and materials obtained. It also favours a reducionistic mentality and international unbalances. The molecular biology of humans, which will follow the complete sequencing of the genome, may foster a rethinking of the concepts of freedom of self-determination (basic for moral responsibility) and of equality. The gene therapy and its possible extension to the betterment of the human species, pose questions of ethical limits to this technology. All these problems will have to be answered in terms of the application of the principle of ethical freedom for self-fulfillment, as a right of the human person, as well as of science and society. Scientific, economic and social interests have to be subordinated to the dignity of the human person. PMID- 1595384 TI - [Ethics in medical research]. PMID- 1595383 TI - [Ethical aspects of prenatal screening and diagnosis]. AB - The general principles of the European Council's draft Recommendation on Prenatal Screening and Diagnosis are presented. Those principles include the conditions for performing prenatal tests, the need for previous genetic counselling, and for fully informed consent, and the ethical rules for the use of individual data gathered. PMID- 1595385 TI - [Left cor triatriatum. Clinical and echocardiographic polymorphism]. AB - Four cases of cor triatriatum in children aged from 4 days to 12 months are described. In one case isolated classical form of the disease occurred, and in the other it was associated respectively to ventricular septal defect, anomalous pulmonary venous connexion and persistence of left superior venae cava. One child had successful surgical correction, two died before surgery could be attempted and one waits operation. Relevant clinical and investigational data are described and the role of echocardiography as an excellent diagnostic tool is stressed. We conclude that isolated form of cor triatriatum can simulate primary lung disease and when associated to other cardiac anomalies it has an earlier diagnosis due to early referral. Surgical results and prognosis depend not only on associated anomalies but also on early diagnosis. PMID- 1595386 TI - [Torsion of wandering spleen. An unusual case of abdominal pain]. AB - Wandering spleen is uncommon and of difficult diagnosis. New Imaging Modalities (Eco; TC), can suggest or confirm the preoperative diagnosis of wandering spleen, permitting conservative surgery, mainly in children. We report two cases of wandering spleen. The first one, with acute surgical abdomen and tumor on left iliac fossa, operated as an ovarian cyst torsion: the laparotomy showed a necrotic spleen in pelvis. The second case presented as intestinal sub-occlusion with recurrent abdominal pain, and a left iliac fossa movable tumor. It was diagnosed by eco and radionuclides before laparotomy. Even diagnosed in different ways, the surgical treatment was the same. PMID- 1595387 TI - [Headache of cervical origin]. AB - It has been known for many years that headaches can originate from abnormalities in the neck. However, their clinical pictures were never sufficiently systematized, at least not enough to allows for research on their pathogenesis. In 1983 Sjaastad et al. described a group of patients with a very uniform and stereotyped headache. Attacks of mild, longlasting, unilateral head pain without side-shift, occurred every few weeks. The headache could be provoked by neck movements, such as extension, rotation or lateral flexion, as well as by external pressure on the neck, eventually spreading to the ipsilateral orbito-frontal temporal or facial areas. The denomination Cervicogenic Headache (CC) was proposed. Its pathophysiology is presently unknown. The C2 and occipital nerve blockages eliminate the pain. The authors present a typical CC case and make some comments on its clinical picture, pathophysiology, and treatment. PMID- 1595388 TI - [Cerebrovascular disorders in young subjects and deficit of protein S]. AB - The authors describe a right hemiparesis and global aphasia, suddenly developed in a 33-Year-old woman, with a previous aphasia, 7 years ago, from which she recovered without sequels. They discuss the relationship between protein inhibitor of blood coagulation and arterial thrombosis, and make references to what has been published about it. PMID- 1595389 TI - [Letters in reference to the article published in Acta Medica Portuguesa 1991; 4:221-225]. PMID- 1595390 TI - Results of reoperation for failed microvascular decompression. AB - Among 64 patients with hemifacial spasm (HFS) and 60 with trigeminal neuralgia (TN) treated by microvascular decompression (MVD), repeated MVD performed on 3 cases with HFS resulted in the absence of spasm in all cases. In 7 cases with TN, this technique resulted in complete remission in 2, recurrence in 3, and no pain relief in 2 cases. MVD was more effective on HFS than on TN in repeated procedures as well as for initial treatment. The cause of recurrence of HFS was attributed to the inadequate cushion effect of muscle as a prosthesis, while that for TN was suspected to be related more to post-operative fibrotic adhesions formed around the fifth nerve. PMID- 1595391 TI - Ossification of the posterior cervical longitudinal ligament. AB - Forty patients with cervical myelopathy due to OPLL (Ossification of the Posterior Longitudinal Ligament) of the cervical spine were studied. According to Abe's or Yamamoto's classification, 12 of them had a 50% decrease in the cross sectional area of the spinal canal. Subtotal vertebrectomy was carried out in 8 of these patients and the remaining 4 patients received posterior decompression. We concluded that anterior decompression, if possible, is the treatment of choice and posterior decompression is recommended only for the longitudinal type involving more than 3 segments. PMID- 1595392 TI - Immunocytochemical study of progesterone receptor in human meningioma. AB - Progesterone (PR) and oestrogen (ER) receptors were examined in meningiomas from 36 patients, using immunocytochemistry. The present experiments were performed to evaluate: (a) the presence and intracellular localization of these receptors, (b) whether PR immunostaining can be correlated (or not) with proliferation potential, as evaluated by histopathological features or the clinical evolution of this neuropathological tumour. Twenty six tumours (72%) tested were positive for PR but none for ER. The presence of PR immunostaining was more frequently observed in females (79% versus 58% in males) and premenopausal status (84% versus 3/5 in postmenopausal). Correlations of PR immunostaining with the histologic type showed 89% of meningothelial, 4/6 cases of transitional, 1/3 case of fibroblastic and 1/4 cases of anaplastic meningiomas to be immunostained for PR. Staining was confined to tumours arachnoidal cells. A heterogeneous distribution was observed in most PR-positive meningiomas. The preferential immunostaining in meningothelial histological types correlates with the presence of PR in normal arachnoidal cells. The proliferating potential of these meningiomas was evaluated by the immunostaining of an antigen only present in proliferating cells (Ki antigen). There was no significant correlation between PR status and the Ki labelling rate, or rapid clinical evolution. These data were compared with those previously reported. They confirm that the cellular biosynthesis of PR in meningiomas is not oestrogen regulated as it is in other sex steroid tissues, such as the breast and the endometrium. PMID- 1595394 TI - Intracranial volume reserve determination using CT images, numerical analysis and lumbar infusion tests. An experimental study. AB - The epidural balloon compression model in the cat was used in intracranial volume reserve studies. The evaluation of the intracranial volume-pressure relations was based on the lumbar infusion test data: intracranial pressure, CSF outflow resistance, volume-pressure response and on CT images numerical analysis (CTINA) values. Two methods were applied and compared in the study: lumbar infusion test and CT images numerical analysis. The determinations were performed at the balloon volumes of 0.5 ml, 1.0 ml, and 1.5 ml. First statistically significant changes were found at the balloon volume of 0.5 ml i.e. the increase of CSF outflow resistance and volume-pressure response (data obtained in lumbar infusion test) and the decrease in CTINA values. The rise of intracranial pressure was less informative as it was observed at the balloon volume of 1.5 ml. Therefore CTINA seems to be a very useful noninvasive screening method in clinical studies of intracranial volume reserve. PMID- 1595393 TI - The no-reflow phenomenon is a post-mortem artifact. AB - Post-ischemic reperfusion impairment, ("no-reflow phenomenon"), was studied in rats subjected to 8-30 minutes of global brain ischemia. During ischemia, rapid and complete loss of cerebral blood flow, EEG and 31P-high energy phosphates (ATP/PCr) was observed. Brain intravascular perfusion defects were examined by injecting carbon black intravenously in a group of rats with stable cardiopulmonary function and in another group subjected to rapid thoracotomy and intraarterial infusion of the carbon marker. Results indicate that global brain ischemic or non-ischemic control rats given intraarterial carbon black after thoracotomy had varying degrees of vessel filling defects in brain resulting in "pale tissue areas" suggestive of impaired perfusion (no-reflow). All rats given carbon black intravenously whether global brain ischemic or not, showed normal cerebrovascular filling of the carbon black and absence of "pale tissue areas". In addition, post-ischemic cerebral reperfusion following 8-30 minutes global brain ischemia can reverse neuroelectric, energy metabolite and cerebral blood flow loss in rats whose cardiopulmonary function is not compromised. These findings indicate that the "no-reflow phenomenon" is an agonal or post-mortem artifact observed in the presence of cardiopulmonary failure. PMID- 1595395 TI - Cerebral blood flow and intracranial pressure during experimental subarachnoid haemorrhage. AB - The relationships of intracranial pressure (ICP), systemic blood pressure (SBP) and cerebral blood flow (CBF) during experimental subarachnoid haemorrhage were investigated in cats. Continuous monitoring of regional cerebral blood flow (rCBF) was done by a thermal diffusion method using a Peltier stack. During haemorrhage ICP rose within 5.4 +/- 0.97 minutes from 10.5 +/- 4.9 to 176.1 +/- 27.8 mmHg. This strong increase of ICP resulted in a temporary arrest of cerebral circulation. The Cushing response during the haemorrhage could not improve the cerebral circulation, but in contrast caused a further increase of ICP. After the haemorrhage the cerebral blood flow normalised within minutes. It is concluded, that the Cushing response during a subarachnoid haemorrhage should be regarded as a deleterious rather than a beneficial mechanism. PMID- 1595397 TI - Intra-operative screw trimming in direct screw fixation of the odontoid process fracture--technical note. AB - For a satisfactory direct screw fixation of fractures of the odontoid process it is necessary to use a screw of the proper total length and thread length, but such an optimal ready-made screw is not always available. The authors describe a technique of intra-operative screw trimming using a high-speed diamond drill. This adjustment is easily and quickly performed. It enables the screw to act as a compression screw, which facilitates fusion of the fractured surfaces. PMID- 1595396 TI - The role of bradykinin in the etiology of vasogenic brain edema and perilesional brain dysfunction. AB - The feline infusion model of brain edema was used to evaluate the role of bradykinin in the etiology and pathophysiology of vasogenic brain edema. Bradykinin (3 or 90 ug in 600 microL saline) did not alter normocapnic regional cerebral blood flow (rCBF) nor induce specific changes in either the somatosensory (SEP) or motor (MEP) evoked potentials. The mean increases in ICP (from 4.5 to 16.1 mmHg) and peri-infusion white matter water content (from 69.4 to 79.8 ml/100 g tissue), mean decrease in lumped craniospinal compliance (from 0.040 to 0.014 ml/mmHg) and local histological changes were all similar to those after 600 microL saline infusion. The interstitial bradykinin infusion caused focal blood-brain-barrier (BBB) opening to Evans Blue dye and was chemotaxic for granulocytes. After the infusion there was a global loss of rCBF CO2 reactivity but there was no ischemia at normocapnia. These results show that bradykinin in brain edema fluid, at concentrations greater than those found in neuropathological conditions, can open the BBB of normal cerebral parenchymal capillaries and cause vascular dysregulation. In neuropathological conditions bradykinin may therefore potentiate formation of vasogenic brain edema but does not contribute to perilesional brain dysfunction. PMID- 1595398 TI - Myelomeningocele repair by a combined fasciocutaneous flap closure. Technical note. AB - The principles of myelomeningocele repair have been clearly described in the literature and generally delineate a technique that calls for the dissection and closure of five separate layers: arachnoid, dura, fascia a subcutaneous layer, and skin. We should like to describe our technique of repairing the myelomeningocele defect following dural separation and closure by shifting complete fasciocutaneous tissue blocks from either side of the defect to the midline following dural closure. A full thickness primary closure can be obtained even in large defects. PMID- 1595399 TI - Spontaneous haematoma as unusual complication of silastic dural substitute. Report of 2 cases. AB - Two cases of an unusual complication of synthetic duraplasty are reported. In both cases, patients had been operated on because of meningiomas and dural defects had been repaired with Silastic. Some years later they developed severe graft-related haematomas and were ultimately successfully treated only by the removal of the synthetic grafts. On the basis of this and other clinical experiences, biological dural grafts seem to be preferable to synthetic ones. PMID- 1595400 TI - Ventriculopleural shunting used as a temporary diversion. AB - Due to the limited absorptive capacity of the pleural cavity, infants and young children are not generally ideal candidates for ventriculopleural shunts. We report using chest cavities as alternate for temporary diversion of CSF in a young child. Venous access to the cervical region could not be utilized because of scarring from previous procedures, while peritoneal access was contraindicated due to repeated pseudocyst formation. Pleural effusions were removed by thoracentesis when necessary, and the shunt catheter was changed to the opposite side of the chest when the effusions reaccumulated within one week. Utilizing the ventriculopleural shunts allowed us to temporize her non-communicating hydrocephalus for a period of one year, until a definitive CSF procedure by direct intracardiac placement of the distal catheter could be performed. PMID- 1595401 TI - Results of routine ventriculostomy with external ventricular drainage for acute hydrocephalus following subarachnoid haemorrhage. AB - We reviewed the results of ventriculostomy with external ventricular drainage in patients with acute hydrocephalus complicating subarachnoid haemorrhage. Of 194 consecutive patients with subarachnoid haemorrhage admitted during the past eight years, 52 (27%) developed hydrocephalus within 72 hours of the ictus. Patients with acute hydrocephalus were in grades III to V (Hunt and Hess) at the time of evaluation and all patients with hydrocephalus underwent ventriculostomy within 24 hours of diagnosis. Twenty-six patients improved within 24 hours of cerebrospinal fluid drainage and 17 of these patients underwent surgery, nine of whom did well (Glasgow Outcome Scale 1 and 2). All 18 patients who did not improve within this period, including one who worsened, died. In eight patients the response to ventriculostomy was considered as undetermined, because of the proximity of the drain insertion to a definitive surgical procedure, and all of them had an excellent outcome (Glasgow Outcome Scale 1). Of 32 patients in grades IV and V, 17 did not improve and all of them died. Eight of the 15 patients in these grades, who were in the improved or undetermined categories, did well. Five patients (10%) developed meningitis. All patients with this complication had drainage for more than four days. Seven patients (14%) had a rebleed during the drainage. All except one patient with a rebleed had no surgery or delayed surgery and in six of them recurrent haemorrhages occurred after more than 24 hours of drainage. We conclude that routine ventriculostomy with external ventricular drainage should be considered for all patients with altered sensorium and acute hydrocephalus following subarachnoid haemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595403 TI - Minimally invasive neurosurgery I. PMID- 1595402 TI - Topographic anatomy of preformed intracranial spaces. AB - This article gives descriptions and measurements of the cerebral ventricles, especially our measurements of the interventricular foramen and the third ventricle. Included are measurements of previous and recent research. The results of endoscopic reviews of the lateral, third and fourth ventricles are also discussed. The subarachnoid spaces are described and illustrated by our corrosion casts. During endoscopic inspection of the subarachnoid spaces, the transcisternal veins are extremely vulnerable. Therefore, these veins in the anterior, middle and posterior cranial fossae are described. PMID- 1595404 TI - Endofiberscopic intracranial stereotopography and endofiberscopic neurosurgery. AB - The possibilities of endoscopic operative procedures in preformed and artificial intracranial and intracerebral cavities are described. Endoscopic investigations were carried out on 166 cadavers; death was due to extracranial pathology and severe brain injury. 132 patients with intracranial lesions were operated on endoscopically. An extended description of endofiberscopic intracranial topographical relationships and endofiberscopic neurosurgical approaches is given. Endoscopic stereotopography of more than 130 intracranial structures is studied. PMID- 1595405 TI - Technological fundamentals of endoscopic haemostasis. AB - In order to perform endoscopic haemostasis there exist several different mechanical, biochemical and thermal methods, which may be applied together with rigid or fully flexible endoscopes in different situations. The technological fundamentals of convective, conductive and radiative heat transfer, the irradiation with coherent electromagnetic waves like microwaves and laser radiation and the resistive heating by RF-current are described. A review of the state of the art of haemostatic coagulation by laser radiation (photocoagulation) and radio-frequency currents (surgical diathermy, high-frequency coagulation) is given. The wavelength-dependent interactions of coherent light waves are compared especially for the three mainly different laser types, i.e., carbon-dioxide-, neodymium-YAG- and argon-ion-laser. The well-known disadvantages of the conventional RF-coagulation are overcome by the so-called electrohydrothermosation (EHT), i.e. the liquid-assisted application of resistive heating of biological tissues to perform haemostasis. Different technological solutions for bipolar RF-coagulation probes including ball-tips and forceps are shown and the first experimental results are discussed in comparison. PMID- 1595406 TI - Ultrasound stereotaxic endoscopy in neurosurgery. AB - Stereotaxic endoscopy assisted by laser- and video technique can be used in a circumscribed number of intracerebral lesions. In the present series of patients, ultrasound imaging has been used as a stereotaxic method to guide the tip of the endoscope to a target area in the depth of the brain via a burr hole in the cranial vault. Initial experience has been obtained in the evacuation of various intracerebral and ventricular as well as cerebellar haematomas; moreover, ventricular tumours can be laser-coagulated and resected. In cases of cystic hemispheric tumours biopsies can be taken under visual control and the inner surface coagulated with laser. The method is less traumatic compared to conventional neurosurgery. PMID- 1595407 TI - Fenestration of intraventricular cysts using a flexible, steerable endoscope. AB - Multiloculated hydrocephalus with multiple intraventricular septae due to meningitis associated with ventriculitis and other CSF containing intraventricular cysts can be treated by endoscopic fenestration. Seven patients with various CSF containing intraventricular cysts were treated using a flexible steerable endoscope and the argon laser. The experience using several currently available steerable endoscopes for treatment of this neurosurgical problem is reviewed. Emphasis is placed on the use of the laser for cyst fenestration. Successful decompression of the ventricular cyst(s) was accomplished in five cases with the endoscope alone. Craniotomy was required in two patients in order to complete cyst fenestration. It is the author's impression that laser assisted ventriculoscopy with steerable flexible endoscopes is an alternative and oftentimes superior method of treating CSF containing cysts within the lateral ventricles of hydrocephalic patients. Steerable flexible endoscopes designed specifically for neurosurgical use are needed. PMID- 1595408 TI - Application of superfine fiberscope for endovasculoscopy, ventriculoscopy, and myeloscopy. AB - In the past three years, we have used a superfine fiberscope for endovasculoscopy, ventriculoscopy, and myeloscopy. Flexible superfine fiberscope, 0.75 mm in outer diameter, could visualize various intravascular findings. In in vivo canine experiment, sequential changes of thrombus produced by endothelial abrasion by needle or balloon in the canine carotid artery can be clearly seen. And thrombolysis by focal arterial injection of tissue plasminogen activator was sequentially observed. In the clinical study, we could evaluate the stenotic lesions of the subclavian and vertebral arteries before and after balloon angioplasty. During ventriculoscopy, a 2 mm of mini-caliber fiberscope was introduced under ultrasound monitoring, and provided clear visualization of intraventricular tumours. In myeloscopy, draining veins of arteriovenous malformations and nerve roots of the cauda equina could be clearly seen by flexible fiberscope. From these results, it can be said that the superfine fiberscope provides clear and useful visualizations of the interior of vessels, ventricles, and the intrathecal area of the spinal canal. The new applications of this superfine fiberscope for minimally invasive neurosurgery may bring about a marked improvement of therapeutic results. PMID- 1595409 TI - Percutaneous endoscopic laser discectomy (PELD). A new surgical technique for non sequestrated lumbar discs. AB - Basic features and techniques of percutaneous endoscopic laser discectomy are described and the results in 6 patients reported. Indications are: discogenic radicular symptoms, caused by disc protrusions, which do not respond to conservative treatment. Contra-indications are: major neurological deficit, segmental instability and spondylolisthesis, extruded disc prolapse, narrow spinal canal or lateral recess. PMID- 1595410 TI - Neuroendoscopic technique for the operative treatment of septated syringomyelia. AB - The management of septated, chambered syringomyelia has until now been problematic because the usual operative methods cannot secure drainage of all chambers of the cavity. The development of a flexible neuroendoscope affords the possibility to perforate the septa under visual control which subdivide the cavity. We present our experiences with 11 cases of septated syringomyelia, which have been operated upon using a flexible neuroendoscope. PMID- 1595411 TI - Minimally invasive neurosurgery by means of ultrathin endoscopes. AB - The term "minimally invasive neurosurgery" (MIN) is defined and the present indications for MIN are described. They include endoscopic stereotactic interventions, endoscopic evacuations of chronic subdural haematomas and intracerebral mass-haemorrhages, endoscopic spinal and ventriculoscopic procedures. The advantages compared to conventional diagnostic and therapeutic neurosurgical approaches consist of less operative risk and reduced tissue traumatization. Endoscopy makes interventions under (real-time) conditions possible. The operative stress for the patient is minimized. PMID- 1595412 TI - Stereotactic endoscopic interventions in cystic and intraventricular brain lesions. AB - Image guided stereotaxis is an accurate and safe method of directing therapy to target volumes defined in two-dimensional (2D) multiplanes or three-dimensional (3D) perspectives using computer reconstruction of image data. The major limitations of stereotactic techniques are related to a lack of intraoperative visualization and direct monitoring of the procedures and to changes of intracranial coordinates after decompression of cystic lesions or aspiration of cerebrospinal fluid in the management of intraventricular lesions. Endoscopic laser stereotaxis (ELS) involves integration of rigid-flexible endoscopy and Nd YAG laser to 3D-2D multiplanar image-guided stereotactic procedures. The major advantages of ELS include: direct intraoperative visualization, hemostasis, evacuation or resection assessment, and wide exploration of intracranial cavities or ventricles. The technique allows safe aspiration, biopsy, and resection or internal decompression of deep and subcortical intracranial lesions. ELS has proved to be safe and effective in the management of 76 clinical cases and appears to be a promising technique in the management of cystic and intraventricular lesions. PMID- 1595413 TI - Tumour resection by stereotactic laser endoscopy. AB - Recent advances in neuro-imaging have led to the early diagnosis of increasingly smaller and more deeply-seated tumours. Conventional neurosurgical techniques are often not satisfactory to deal with these lesions. The authors describe their preliminary experience with a prototype neuro-endoscope. The technical characteristics of the instrument and description of its use in performing stereotactic laser tumour resection are provided. PMID- 1595414 TI - Volumetric stereotactic resection of superficial and deep seated intraaxial brain lesions. AB - From 1984 to 1989 a total of 374 computer-assisted stereotactic resections based on computed tomography or magnetic resonance imaging were performed on 337 supratentorial and 37 infratentorial brain lesions. Computer-assisted stereotactic volumetric resection allows a more aggressive extirpation of tumours with less damaging of the adjacent brain tissue. This procedure is of most benefit in deep seated circumscribed lesions and of less benefit in infiltrating tumours such as high grade gliomas and in fibrillary astrocytomas located in essential brain areas. PMID- 1595415 TI - "Whole body" stereotaxy: application of stereotactic endoscopy to operations of herniated lumbar discs. AB - In order to minimize surgical trauma of operations for lumbar disc prolapses, a modified Laitinen's stereotactic frame was utilized in nine patients. Stereotactic localization of the lesion could be done accurately in all cases. Percutaneous prolapsectomy and nucleotomy was performed successfully in three patients as a blind stereotactic procedure, whereas in the remaining six cases a microsurgical or conventional operation was needed to accomplish the removal of the prolapse or the discal mass. Application of the endoscopic technique to lumbar disc operations is anticipated to make the percutaneous stereotactic prolapsectomy and nucleotomy a rational alternative to contemporary more invasive procedures. PMID- 1595416 TI - Potential use of robots in endoscopic neurosurgery. AB - A 6-axis stereotactic robot has been designed and linked to a stereotactic frame for routine use. Robot software allows the positioning of a probe holder in order to reach a given target. A calibration step enables the robot to compute the position of the x-ray beam and correct its final position to avoid parallax errors. The co-ordinates of the target are presently taken from anteroposterior and lateral X-rays using a digitizing table. Connection with a digitized angiography system is in progress and will allow direct sampling of numerical data from the x-ray data. Further steps will include connections with a 3D reconstructed image from MRI and CAT as well as with a resident computerized atlas. Present experience after 14 months of daily practice represents 140 stereotactic procedures which can be extended to any special use, including endoscopic approaches. PMID- 1595417 TI - [Spanish adaptation of the Life Skills Profile. Profile of activities of daily living. Structure and factorial composition]. AB - The Spanish version of LSP (Life Skills Profile) including translation and its factorial structure are reported. Its has 39 items and it attempts to measure the chronic mental patient functioning in situations and tasks of everyday life. Factor analysis of this Spanish version has yield five subscales, that although they differ slightly from those proposed by the original authors, they hold strong clinical sense and also show considerable value as indicators of rehabilitative strategies. PMID- 1595418 TI - [Formal changes of thought in schizophrenic, schizophreniform, and manic schizoaffective disorders]. AB - The aim of the present study was to verify the hypothesis that there are formal thought disorders more specific to schizophrenic disorders. The sample was composed of 82 admitted patients who were chosen for two reasons: presence of schizophrenic symptoms and they fulfilled the RDC criteria for schizophrenic or schizoaffective manic disorders. They were subdivided in three groups according to the RDC and DSM-III-R criteria. The first group were twenty eight patients who fulfilled both criteria to schizophrenic disorders, the second group 28 whose fulfilled the RDC but not DSM-III-R criteria of schizophrenic disorder, and the third group were 26 schizoaffective manics in RDC but with diverse diagnoses in DSM-III-R. A factorial analysis was carried out with oblique rotation and one-way analyses of variance of the factors between the diagnostic groups. It resulted in six factors which explained 70% of the variance and were named: disorganization, negative, stylistic, tangential, manic and semantic factors. The schizophrenic patients and significantly loaded in the negative factor with respect to the other groups, and were significantly loaded in the tangential factor with respect to schizophreniform group. The schizoaffective manics were significantly loaded in manic factor respect to the other groups. Therefore there were symptomatological constellations more specific to schizophrenic disorders. Also, significative correlations were found between the disorganization factor and the SANS attention subscale and a lack of correlations between this factor and the positive symptoms. The existence of a new disorganization syndrome was confirmed, which supplements the positive-negative dichotomous model that has been proposed by some authors. PMID- 1595420 TI - [Quantification of the stress reactivity in psychiatric patients admitted to an acute care unit]. AB - We studied stress reactivity in a sample of 48 psychiatric acute inpatients of a psychiatric ward in a general hospital. Stress Reactivity Questionnaire (IRE-32 items) was used, this instrument supplies an index of the subject's individual response to stressful situations. The mean Stress Reactivity Index of the sample was 13.02 (s.d. 6.31), which is significantly higher than that found by us in general population--9.67 (s.d. 5.47)--and similar to the score obtained by psychiatric outpatients in our Department--13.30 (s.d. 6.07). According to gender, women reached the highest score (13.76). The various scores obtained in the Stress Reactivity Index by the different diagnosis are outlined. PMID- 1595419 TI - [Study of the reliability, validity and internal consistency of the LSP scale (Life Skills Profile). Profile of activities of daily living]. AB - The LSP scale (Life Skills profile) has been recently translated and adapted into Spanish language. Its has 39 items and attempts to measure the chronic mental patient functioning in situations and tasks of everyday life. It is brief, jargon free, capable of completion by family members, community housing managers as well as professional staff. Reliability, concurrent validity and internal consistency of this Spanish version are reported. The good performance of LSP in all this measurements give support to its use in research and clinical settings. PMID- 1595421 TI - Accuracy of self-reported weight: covariation with binger or restrainer status and eating disorder symptomatology. AB - Studies indicate that women's self-reported and actual weights correlate above .90 but that approximately one-third of women under-report their weight by more than 5 lb. Overweight women under-report to a greater degree than women of normal weight. The present study replicated these findings and extended them to women showing eating disorder-related behaviors, including regular binging and dietary restraint. Reporting accuracy was also covaried with eating disorder tendencies as measured on a continuum in the general population. Despite high statistical power, results revealed no correlation between under-reporting and either Bulimia Test scores or Eating Attitudes Test scores and found no differences in reporting accuracy as a function of binger status or restrained eater status. Women manifesting eating disorder-relating behaviors were neither more nor less accurate than were normals. Potential sources of error in measuring weight and in evaluating self-report are presented and discussed. PMID- 1595422 TI - Processes of change across five stages of smoking cessation. AB - A cross-sectional design with 190 smokers and exsmokers selected by random digit dialing was used to determine differences in processes individuals use to modify behavior across five stages of smoking cessation. Five stages of cessation are: precontemplation, contemplation, recent quitting, long-term quitting, and relapse. Ten processes of change (POC) or ways individuals modify behavior were assessed. Examples of POCs are: consciousness raising, self-liberation, reinforcement management, and stimulus control. Biochemical validation of smoking abstinence was performed on a random subset of exsmoker subjects. Individuals in five stages of smoking cessation used processes of change differently as reflected by a significant MANOVA, F (40,590) = 5.02, p = .0001. It is important to assess an individual's stage of smoking cessation when planning interventions related to POCs. PMID- 1595423 TI - Effects of setting on the subjective and behavioral effects of d-amphetamine in humans. AB - The effects of setting on the subjective and behavioral effects of 20 mg oral d amphetamine were studied in eight healthy volunteers. A within-subjects design was used in which subjects ingested either amphetamine or placebo capsules in either an inpatient (isolated laboratory room) or an outpatient (normal daily environment) setting. The order of the four experimental conditions was randomized across subjects. Subjective drug effects were assessed using the Profile of Mood States, the Addiction Research Center Inventory, a Visual Analogue Scale, and a Drug Effects/Liking questionnaire, completed prior to and 1, 3, and 6 h after capsule ingestion. In addition, an End-of-Session questionnaire measuring overall drug liking and drug identification was completed at the 6-h timepoint. Subjects wore wrist monitors to record their physical activity levels during the 6-h postingestion period. Amphetamine produced typical stimulant-like subjective effects such as elation, euphoria, and friendliness, but the setting neither quantitatively nor qualitatively altered the drug response. PMID- 1595424 TI - Attendance and outcome in a work site weight control program: processes and stages of change as process and predictor variables. AB - This naturalistic study assessed client changes during treatment and identified salient predictors of therapy attendance and outcome. Subjects were assessed on processes and stages of change, self-efficacy, social support, weight history (including expectations, goals, and reasons for losing weight), and demographics at the beginning, middle, and end of a 10-week, behaviorally oriented work site program for weight control. Significant shifts from contemplation to action occurred for clients remaining in treatment. There were also significant modifications in the use of change processes as a result of treatment: counterconditioning, contingency management, stimulus control, interpersonal control, and social liberation increased while medication use, wishful thinking, and minimizing threats decreased. Change processes employed during the early portion of the group treatment were the best predictors of treatment attendance and outcome, superior to self-efficacy, social support, weight history, and demographic variables. The results supported a transtheoretical model that emphasizes dynamic processes and stages as core dimensions for understanding how people change. PMID- 1595425 TI - Alcoholism, politics, and bureaucracy: the consensus against controlled-drinking therapy in America. AB - Controlled drinking has long been rejected as a therapeutic goal in traditional American alcoholism treatment. More striking has been the adoption of this position by behaviorists who once fostered controlled-drinking (CD) therapy, such as Peter Nathan, former director of the Rutgers Center of Alcohol Studies. This shift has occurred even while the evidence for rejecting the value of moderation training is unclear. Rather than being justified empirically, this rejection must instead be understood as a strategy behaviorists have used to jettison a politically explosive element in the behavioral package in order to gain overall acceptance for the behavioral approach to treating alcoholism. However, this strategy entails significant scientific, clinical, social, and ethical costs. PMID- 1595426 TI - Schizencephaly and nonlissencephalic cortical dysplasias. PMID- 1595427 TI - Chiari III malformation: imaging features. AB - PURPOSE: To analyze and discuss the MR and CT features of Chiari type III malformations. PATIENTS AND METHOD: MR and CT studies in nine neonates born at term with Chiari type III malformations were retrospectively reviewed. RESULTS: High cervical/low occipital encephaloceles were present in all cases. Hypoplasia of the low and midline aspects of the parietal bones was seen in four patients. The encephaloceles contained varying amounts of brain (cerebellum and occipital lobes, six cases; cerebellum only, three cases), ventricles (fourth, six cases; lateral, three cases), cisterns, and in one case, the medulla and pons. Associated anomalies included: petrous and clivus scalloping (five cases/nine cases), cerebellar hemisphere overgrowth (two cases/nine cases), cerebellar tonsillar herniation (three cases/seven cases), deformed midbrain (nine cases), hydrocephalus (two cases/nine cases), dysgenesis of the corpus callosum (six cases/nine cases), posterior cervical vertebral agenesis (three cases/eight cases), and spinal cord syrinxes (two cases/seven cases). In four patients who underwent surgical resection and closure, aberrant deep draining veins and ectopic venous sinuses within the encephaloceles were found. Pathology examination of the encephalocele (four cases/nine cases) showed multiple anomalies (necrosis, gliosis, heterotopias, meningeal fibrosis) that were not demonstrable by either MR or CT. The marked disorganization of the tissues contained within the cephalocele may account for the lack of MR sensitivity to these abnormalities. CONCLUSION: Preoperative determination of the position of the medulla and pons is essential and is easily accomplished by MR. To avoid surgical complications, the high incidence of venous anomalies should be kept in mind. PMID- 1595428 TI - The large temporal horn: MR analysis in developmental brain anomalies versus hydrocephalus. AB - PURPOSE: To utilize MR to delineate the morphologic abnormalities of the temporal horn and adjacent structures in patients with congenital brain anomalies and to differentiate these findings from the temporal horn alterations in obstructive hydrocephalus. PATIENTS AND METHODS: Thirty-six patients were included in this retrospective study, including eight with agenesis of the corpus callosum (ACC), four with lissencephaly (lis), four with lobar holoprosencephaly (holo), as well as 20 with isolated obstructive hydrocephalus due to tumor (17 patients) or aqueductal stenosis (three patients). Twenty patients with normal scans were included as controls. RESULTS: Coronal plane image analysis showed that 75% of patients with brain anomalies had enlargement of the temporal horns, most prominently involving the inferolateral aspects of the ventricle (8/8 ACC, 4/4 lis, 0/4 holo). Hippocampal formations were small in 62% (6/8 ACC, 3/4 lis, 1/4 holo). An abnormal, vertical orientation (incomplete inversion) of the hippocampal formations was observed in 82% (8/8 ACC, 4/4 lis, 1/4 holo). Focal thinning of the white matter lateral to the temporal horn was seen in 50% (8/8 ACC, 0/4 lis, 0/4 holo). All patients with isolated obstructive hydrocephalus showed enlargement of the temporal horns, most pronounced in the superior-lateral region. Hippocampal formations showed normal, horizontal orientation (complete inversion) and were of normal size in 17 of 20 patients; the only exceptions included patients with severe hydrocephalus where the hippocampi were flattened along the inferior margin of the temporal horn. Temporal lobe white matter was normal in the 17 patients with mild or moderate hydrocephalus: diffuse white matter thinning inferolaterally was observed in the three patients with severe hydrocephalus. Distinct differences were present in the morphology of the temporal horn and surrounding brain in congenital brain disorders compared with those in patients with hydrocephalic. The anomalous brains showed enlargement as a result of incomplete development, and the hydrocephalic brains showed enlargement as a result of increased intraventricular pressure. CONCLUSION: Temporal horn enlargement in lissencephaly and agenesis of the corpus callosum should not be misinterpreted as hydrocephalus. Analysis of temporal lobe morphology will allow differentiation if doubt exists. PMID- 1595429 TI - Walker-Warburg syndrome. AB - The Walker-Warburg syndrome (WWS) is a rare autosomal recessive disorder characterized by lissencephaly, cerebellar and retinal malformations, and congenital muscular dystrophy. We report a new case of WWS identified with the aid of cranial MR and briefly review the radiologic findings of this lethal syndrome. PMID- 1595430 TI - Gd-DTPA-enhanced 3D MR imaging of cervical degenerative disk disease: initial experience. AB - PURPOSE: To assess whether a single enhanced T1-weighted gradient echo volume sequence, with the appropriate reformatted images, could be equivalent to a more conventional 2D set of MR sequences for the evaluation of cervical extradural degenerative disk disease (bony canal and foraminal stenosis; disk herniation). MATERIALS AND METHODS: Sixty-one patients evaluated for extradural degenerative disease by MR were imaged with a "standard" MR examination (Sagittal T1-weighted spin echo, axial low flip angle gradient echo), were then given 0.1 mmol/kg Gd DTPA intravenously, and reimaged with either a 3D FLASH (fast low angle shot), TR 40/TE 7/1 excitation), 40 degree flip angle, acquired as 64, 2-mm sagittal partitions, or a 3D turbo FLASH (MP RAGE-magnetization prepared rapid acquisition gradient echo) (10/4/1), 10 degree flip angle acquired as 128, 2-mm coronal partitions. The volume sequences were reconstructed in the axial plane, and right and left 45 degree oblique coronal planes. The two sets of examinations (standard vs volume) were prospectively interpreted by two neuroradiologists for quality of examination, and location, type, and severity of extradural degenerative disease in a random, blinded, independent fashion. RESULTS: There was no significant difference between the standard examination and the 3D MP RAGE for central extradural disease. The 3D FLASH examination was significantly worse than the standard examination in identification of central extradural disease, with an average of 21 herniations not identified, or underestimated in size. Neither the 3D FLASH, nor the 3D MP RAGE examinations showed any significant improvement compared to the routine 2D examination for the location and severity of foraminal disease. CONCLUSION: If extradural degenerative disk disease is being evaluated, then a single enhanced 3D T1-weighted imaging sequence taking 6 minutes can be equivalent to a routine set of mixed 2D spin echo and low flip angle gradient echo sequences. PMID- 1595431 TI - The nuclear trial sign in thoracic herniated disks. AB - PURPOSE AND METHODS: Postmyelography CT studies of 84 patients with 114 thoracic herniated disks were reviewed for endplate irregularity, sclerosis, and/or disk space calcification that could suggest a migratory path of the herniated fragment. RESULTS: Abnormal straight or curvilinear densities (the "nuclear trial sign") were present at the level of the disk or endplate in 46% of the cases. MR studies of 35 thoracic herniated disks were also examined. Similar changes were likewise present in 44%. CONCLUSION: The frequent occurrence of this finding in the mid and lower thoracic spine renders it a useful secondary sign for thoracic herniated disks, although false positives do occur. PMID- 1595432 TI - MR imaging of spinal cord and vertebral body infarction. AB - PURPOSE: To study the usefulness of MR in the evaluation of spinal cord infarctions and associated findings. MATERIALS AND METHODS: MR examinations of 12 patients (10 men and two women) were reviewed retrospectively. Onset of symptoms of spinal cord ischemia was abrupt in all patients; MR was performed 8 hr to 4 months after onset. Contrast-enhanced MR was performed in four of the patients. RESULTS: Abnormal MR findings of the spinal cord included abnormal cord signal (11 of 12), best demonstrated on T2-weighted images, and morphologic changes (cord enlargement during the acute phase in nine patients and cord atrophy during the chronic phase in two), best demonstrated on T1-weighted images. Vascular abnormalities (aortic) were detected by MR in four of the 12 patients. Three of these four patients also had abnormal bone marrow signal, predominantly in the anterior half (one) or in multiple areas near the endplate and/or deep medullary portion of the vertebral body involving several vertebrae (two). T1-weighted images were not sensitive in detecting signal changes in either the bone marrow (two of three) or spinal cord (nine of 12). Enhanced MR imaging was performed in four patients (two in the acute phase and two in the chronic phase) and showed diffuse enhancement of the spinal cord proximal to a relatively unenhancing distal conus in one of the two patients imaged during the acute phase. No abnormal enhancement was noted in the other three patients. CONCLUSION: MR is a useful means of detecting spinal cord infarction and associated vascular and bony changes. The patterns of bone marrow abnormalities reflect the underlying pathophysiology of the blood supply to the spinal cord and bone. The associated vascular and bone marrow abnormalities serve as additional information for the diagnosis of spinal cord infarction. PMID- 1595433 TI - Total cerebrospinal fluid enhancement following intravenous Gd-DTPA administration in a case of meningiomatosis. PMID- 1595434 TI - Spinal cord infarction and fibrocartilagenous emboli. PMID- 1595435 TI - Lumbar synovial cysts eroding bone. PMID- 1595436 TI - Pigmented villonodular synovitis of a lumbar facet joint. AB - We describe the CT appearance of suspected pigmented villonodular synovitis involving a lumbar facet in a 51-year-old woman, and discuss how the histologic and radiologic appearances may differ from those of synovial cysts. PMID- 1595437 TI - Pigmented villonodular synovitis and synovial cysts of the spine [ comment]. PMID- 1595438 TI - Biopsy of vertebral and paravertebral structures with a new coaxial needle system. PMID- 1595439 TI - Flow dynamics in the human carotid artery: I. Preliminary observations using a transparent elastic model. AB - PURPOSE: We developed an elastic, transparent, life-size model of the cranial vessels that allowed us to visualize carotid artery flows directly, and wish to report our observations and recorded data. MATERIALS AND METHODS: The brachiocephalic arteries of 12 adult cadavers were cannulated and infused with acrylic. The heads were dissolved in alkali and, using a "lost wax" technique, a silicone model that reflected the shape and size of the original artery was produced. These models were connected to a closed circuit of flowing fluid. The fluid was rendered opaque by injecting isobaric dyes at various points in the streams. RESULTS: These dye opacified slipstreams showed a relatively low flow area visible in the posterior and lateral aspect of the carotid bulb that acted as an internal buffer, and directed the more posterior lateral slipstreams anteriorly and at the same time increased their velocity. The cervical internal carotid artery was relatively straight and showed flow patterns that were essentially laminar. In the petrous internal carotid artery, the dye-opacified slipstreams began a helical flow pattern, and areas of flow reversal became apparent along the inner aspect (lesser curvature) of the bend. The central slipstreams tended to flow in a straighter line, passing close to, and sometimes striking the wall of, the outer portion (greater curvature) of the bend. In the cavernous internal carotid artery, helical flow continued. The central slipstreams struck the outer surface (greater curve) of the arterial bend. The point that the central slipstream struck the wall was more distal during systole than during diastole. At the supraclinoid section laminar flow again became established. Certain slipstreams selectively entered individual cranial branches. CONCLUSION: The model we describe should allow more accurate study of complicated flow dynamics in vessels supplying the brain. PMID- 1595440 TI - Intracranial aneurysms: flow analysis of their origin and progression. AB - PURPOSE: To explain the origin and growth of intracranial aneurysms using the hemodynamic data obtained from a computer simulation. MATERIALS AND METHODS: Pulsatile flow in an intracranial aneurysm cavity was numerically simulated based on physiologic pulsatile flow observed in the aorta. A finite element method was applied to solve the equations of motion and the non-Newtonian viscosity of blood was taken into account in the analysis. An angiogram of a middle cerebral artery segment with aneurysm was used for the computer modeling of blood flow within the aneurysm cavity. Local shear stress and pressure on the wall at the neck of the aneurysm as well as blood flow motions inside the cavity were calculated as a function of time for various stages in the development of the aneurysm. FINDINGS: Blood moves into the aneurysm cavity along the proximal wall of the cavity and emerges along the distal wall during the acceleration period of systole; however, during the deceleration period of systole and diastole, blood changes its flow direction, entering along the distal wall of the cavity and leaving along the proximal cavity wall. Rapid changes of blood flow direction result in rapid changes in wall shear stress and pressure at the proximal and distal walls of the cavity, rendering continuous damage to the intima at the cavity neck. These hemodynamic stresses relate to the anatomy of a particular vessel may be responsible for the initiation of aneurysm formation and subsequent progression, thrombosis and/or rupture. CONCLUSION: Computer modeling can further our understanding of factors that determine the origin and progression of intracranial aneurysms. PMID- 1595442 TI - Gadolinium-enhanced MR of the postoperative internal auditory canal following acoustic neuroma resection via the middle fossa approach. AB - PURPOSE: To evaluate the ability of gadolinium-enhanced MR in detecting recurrent tumor in patients whose acoustic neuromas were surgically removed via the middle cranial fossa approach. PATIENTS AND METHODS: Postoperative gadolinium-enhanced exams of 13 of 44 patients who underwent excision of acoustic neuromas via the middle cranial fossa approach were reviewed. RESULTS: Postoperative enhancement was seen in 12 of the 13 patients; two patients underwent serial exams without significant change. On the basis of a single exam, we were unable to conclusively differentiate postoperative enhancement from residual or recurrent tumor. CONCLUSIONS: A single exam is of limited value. Serial studies are recommended to identify changes that would indicate tumor growth. A proposed MR follow-up schedule is an initial baseline exam within 2 months of surgery and a repeat exam during the second postoperative year. PMID- 1595441 TI - Proton relaxation enhancement associated with iodinated contrast agents in MR imaging of the CNS. AB - PURPOSE: To study the effects of iodinated radiographic contrast agents on proton relaxation in MR imaging. PATIENTS AND METHODS: Two patients were evaluated after the intrathecal administration of an iodinated nonionic contrast agent (Isovue) and five subjects with cranial tumors following the intravenous administration of an iodinated ionic contrast medium (Renografin). RESULTS: Both patients with subarachnoid iodinated contrast media demonstrated a relative reduction in T1 and/or T2 times using a spin-echo sequence, while four of five of the subjects with intracranial tumors (one glioma, one dural metastasis, three meningiomas) and intravenous enhancement revealed a visible MR effect. Confirmation of these in vivo observations was obtained by in vitro measurement of T1 and T2 while varying the concentration of the contrast media in saline. All iodinated contrast media showed progressively reduced relaxation times (T1 and T2) as the concentration of the agent was increased. The largest contributing relaxation mechanism is probably due to the binding and exchange of the surrounding water with the contrast molecules. CONCLUSION: The observed T1/T2 effects suggest that administration of iodinated contrast media in the period immediately prior to MR scanning may be contraindicated in selected cases due to the demonstrated alteration of MR signal intensity that may lead to diagnostic inaccuracies. PMID- 1595443 TI - CT of severe inner ear anomalies, including aplasia, in a case of Wildervanck syndrome. PMID- 1595444 TI - Primary mucocele of the petrous apex: MR appearance. AB - Mucoceles of the petrous apex are rare. Their MR appearance varies depending on the degree of hydration or inspissation of the contents. Concise preoperative diagnosis is helpful, since mucoceles are better drained to the mastoids via an infralabyrinthine approach rather than the more risky middle cranial fossa approach used for cholesteatomas. PMID- 1595445 TI - Cystic temporofacial rhabdomyosarcoma with subarachnoid communication. PMID- 1595446 TI - A palatal dentigerous cyst arising from a mesiodente. AB - Dentigerous cysts can develop from unerupted primary, permanent, or rarely supernumerary teeth. When a supernumerary tooth is in the maxilla, near the midline, it is called a mesiodente. Such a mesiodente lies in the palate and a cyst developing about this tooth can extend directly up into the nasal fossae. More commonly a dentigerous cyst arising from unerupted maxillary teeth occurs about the molar, premolar, or canine teeth and the cyst extends up into the maxillary sinus. The CT and MR findings in a rare case of a dentigerous cyst of a mesiodente are presented. PMID- 1595447 TI - Ludwig angina: an uncommon and potentially lethal neck infection. PMID- 1595448 TI - CT of muscle necrosis following radiation therapy in a patient with head and neck malignancy. AB - Radiation-induced changes within skeletal muscle may be seen on follow-up CT or MR scans in patients who have undergone postoperative radiation therapy for head and neck tumors. Because they may mimic recurrent disease, these changes should be borne in mind. PMID- 1595449 TI - Selective MR imaging approach for evaluation of patients with Horner's syndrome. AB - PURPOSE: To assess the usefulness of MR in the evaluation of patients with Horner's syndrome. PATIENTS AND METHODS: We prospectively performed MR imaging in 33 patients with Horner's syndrome (13 preganglionic and 20 postganglionic) using a protocol specifically designed for pre- and postganglionic varieties of this syndrome. Assignment of patients to pre- or postganglionic categories was performed on the basis of pharmacologic testing. RESULTS: Abnormalities in one half of the patients with preganglionic Horner's syndrome included lateral medullary infarct, spinal cord/root disease, apical lung tumor, and paravertebral metastatic mass. Three of 20 patients with postganglionic Horner's syndrome had carotid artery dissection. CONCLUSION: Routine scanning of patients who have postganglionic Horner's syndrome with cluster headaches was not helpful in our small series. PMID- 1595450 TI - Optic nerve sarcoidosis: MR findings. AB - Neurologic involvement has been described in 5% of patients with sarcoidosis; however, direct granulomatous involvement limited to the optic nerve but not involving the chiasm is rare. We describe two patients with biopsy-proven sarcoidosis; the fat-suppressed gadolinium-enhanced MR findings showed sarcoid involvement limited to the optic nerves. PMID- 1595451 TI - Transorbital herniation: an unusual mechanism of intracranial decompression following trauma. PMID- 1595453 TI - How the brain got its names and numbers. PMID- 1595452 TI - Radiation-induced optic neuropathy: characteristic appearances on gadolinium enhanced MR. AB - PURPOSE: To assess the value of contrast-enhanced MR in the evaluation of radiation-induced optic neuropathy. MATERIALS AND METHODS: Three patients with rapid visual loss 1 1/2 to 3 years after radiation therapy to the optic nerves were studied with gadopentetate dimeglumine-enhanced MR images. All patients received over 5000 cGy, experienced rapid, permanent visual loss over several days to weeks, and underwent MR within weeks of presentation. RESULTS: Enhanced MR images on each patient revealed focal discrete enhancement of the intracranial optic nerve. One patient underwent biopsy of the enhancing segment; this revealed pathologic changes of radiation optic neuropathy. Optic nerve enhancement in a patient with visual loss and a prior history of radiation therapy to the orbits or optic nerves suggests radiation optic neuropathy. CONCLUSION: Contrast enhanced MR of the orbits, optic nerves, and chiasm is the imaging test of choice in patients with vision loss after radiation therapy for sellar or skull base disease; MR findings may obviate the need for biopsy. PMID- 1595454 TI - Placement of intracerebral depth electrodes during excisional surgery for epilepsy: value of intraoperative ultrasound. AB - The authors describe the use of intraoperative US for directing placement of depth electrodes for the localization of seizure foci prior to temporal lobectomy. They used this technique in seven patients (six undergoing temporal and one frontal resection), and encountered no complications. PMID- 1595455 TI - Thrombus localization with emergency cerebral CT. AB - PURPOSE: To determine the prevalence of the hyperdense middle cerebral artery sign (HMCAS) in an acute stroke population (treated with intravenous tissue plasminogen activator (tPA) within 90 minutes of stroke onset); to correlate the presence/absence of the sign with arteriographic findings; and to correlate the HMCAS with the volume of subsequent infarction. PATIENTS AND METHODS: 55 patients with acute ischemic stroke underwent CT to exclude cerebral hemorrhage and were then treated with intravenous tPA. The neuroradiologist, blinded to the clinical and arteriographic data, sought the HMCAS on the initial and subsequent scans. RESULTS: The HMCAS was detected by CT in 19 of 55 (34.5%) patients (one false positive). Arteriograms in 14 of the 18 true positive patients confirmed the CT predicted middle cerebral artery segment in 12. The 18 patients developed infarcts larger than patients not exhibiting the sign (132 cc vs 52 cc, P less than .002). CONCLUSION: The HMCAS does predict middle cerebral artery occlusion and subsequent development of a large infarct. PMID- 1595456 TI - Xe/CT cerebral blood flow evaluation of delayed symptomatic cerebral ischemia after subarachnoid hemorrhage. AB - PURPOSE: We examined the xenon/CT method of measuring cerebral blood flow in assessing the location, pattern of onset, and severity of delayed cerebral ischemia. PATIENTS AND METHODS: Fourteen patients with delayed neurologic deficits due to ischemia were selected from a group of 66 patients with subarachnoid hemorrhage. All blood flow studies were performed within 12 hours of deterioration and at regular intervals during medical management. RESULTS: In 10 of the 14 patients, noncontrast CT did not identify a cause for deterioration, whereas the blood flow study revealed diminished flow values. Location of blood flow reduction was variable. In five of the 14 patients, blood flow reduction was closely related anatomically to the vessel of aneurysm origin. In another three, blood flow reduction was anatomically remote to the vessel of origin. The remaining six experienced local and remote cerebral blood flow reduction. Six of 14 patients suffered sudden, devastating deterioration, refractory to therapy and associated with blood flow of 15 cc/100 g.min or less, resulting in local or widespread infarction. The remaining eight had less severe blood flow reduction and did not infarct those territories. CONCLUSIONS: Vasospasm can affect remote vessels as severely as local vessels and can affect remote vessels alone. Diminished cerebral blood flow correlated closely with clinical vasospasm in this group of patients. Xenon/CT cerebral blood flow studies can identify tissue at risk of infarction when CT is normal. PMID- 1595457 TI - Contrast-enhanced MR of cerebral arteritis: intravascular enhancement related to flow stasis within areas of focal arterial ectasia. AB - The authors present a case of probable amphetamine-induced cerebral arteritis in a 31-year-old man with AIDS, testicular carcinoma, and recurrent pneumocystis pneumonia. MR enhancement was demonstrated in areas of focal arterial ectasia, presumably due to slow flow. CT, MR, and angiographic findings were strikingly confirmed postmortem. Angiography remains essential in the diagnosis of cerebral arteritis. PMID- 1595458 TI - Cerebral infarction: assessment of patterns using ultra-fast MR contrast imaging. AB - We describe a rapid MR imaging technique, applying functional analysis to images obtained during the tissue transit of injected contrast material into the cerebral circulation, which has potential for assessment of the altered hemodynamics in cerebral ischemia. This technique utilized turbo-FLASH imaging maximizing the T1 relaxivity properties of gadopentetate dimeglumine with positive contrast enhancement. PMID- 1595459 TI - Aneurysm of the azygos pericallosal artery: diagnosis by MR imaging and MR angiography. PMID- 1595460 TI - Unusual dissection of the proximal vertebral artery: description of three cases. AB - We report three cases that reveal an array of etiologic and radiologic findings associated with dissection of the proximal segment of the vertebral arteries. Regardless of etiology, the proximal segment may be the principal site of dissection in these vessels. PMID- 1595461 TI - Recurrent Lhermitte-Duclos disease: report of two cases and association with Cowden's disease. AB - Two cases of Lhermitte-Duclos disease (LDD), one associated with Cowden's disease, are reported. Both demonstrated recurrence long after initial surgical resection. There is a propensity for occurrence in the left cerebellar hemisphere. On MR there is hypointensity on T1-weighted images and moderately high signal on T2-weighted images, with parallel linear striations on the surface of the lesion felt to represent dysplastic cerebellar folia. LDD is felt to be a low-grade neoplasm and potential component of Cowden's phakomatosis. PMID- 1595462 TI - Intracranial meningioma. AB - This case shows many of the imaging features classically associated with meningiomas. The illustrations show common location, shape, and local effects as well as enhancement characteristics. Hyperostosis and bone destruction, a fluid "cleft" surrounding the extraaxial mass, gray-white interface displacement, and secondary intraparenchymal changes are correlated with gross pathology findings. These key features are summarized in Table 1 and the composite anatomic diagram (Fig. 6). PMID- 1595463 TI - Gyriform calcifications in tuberous sclerosis simulating the appearance of Sturge Weber disease. AB - Two cases of tuberous sclerosis are presented. Extensive superficial occipital calcifications were found as classically described in Sturge-Weber syndrome. Other radiologic signs of tuberous sclerosis, such as subependymal calcifications in both patients and surgically proved giant cell astrocytoma in one patient, were present. At pathologic examination, the calcifications appeared to be located in extensive cortical tubers. PMID- 1595465 TI - Buffing up MR images. PMID- 1595464 TI - Bilateral trigeminal schwannomas associated with von Recklinghausen disease. PMID- 1595466 TI - Preembolization functional evaluation in brain arteriovenous malformations: the superselective Amytal test. AB - PURPOSE: To describe our experience with the use of Amytal injected through a superselective catheter prior to planned embolization of cerebral arteriovenous malformations. MATERIALS AND METHODS: 109 superselective tests were performed with 30-mg injections of Amytal. All patients were evaluated by both clinical examination and EEG. RESULTS: Twenty-three of these tests were positive. There were no prolonged neurologic complications of the Amytal test. We also examined the value of EEG monitoring compared to clinical monitoring during the Amytal test. Of the 23 positive Amytal tests, only 12 showed a change on clinical exam (52%). This meant that almost half of the positive Amytal tests would have been falsely called negative (false negative rate of 10%). There were also three positive Amytal tests with changes on clinical examination without any change on EEG. CONCLUSION: The superselective Amytal test can be done safely as part of the interventional neuroradiologic procedure. Clinical and EEG monitoring of the patient are essential. PMID- 1595467 TI - Preembolization functional evaluation in brain arteriovenous malformations: the ability of superselective Amytal test to predict neurologic dysfunction before embolization. AB - PURPOSE: To describe the incidence of neurologic dysfunction following embolization of supratentorial AVMs, and to correlate findings with results of preembolization Amytal tests. MATERIALS AND METHODS: Data from 147 embolizations of supratentorial AVMs following Amytal tests in 30 awake patients were analyzed retrospectively. RESULTS: Of five embolizations done after a positive Amytal test, two were followed by neurologic complications. Eighty-two embolizations done as single embolizations immediately after a negative Amytal test were associated with no neurologic complications. The remaining embolizations were parts of multiple series of embolizations, each beginning with an Amytal test and followed by a number of embolizations without catheter movement or repeat Amytal testing. Since any prior embolization in the series might reduce the sump effect of the AVM, embolic agent delivered later in the series could potentially reach functional brain tissue not fully tested by the Amytal test. Therefore, repeat embolizations (not immediately preceded by an Amytal test) were considered separately. In 60 repeat embolizations, six (10%) were associated with some neurologic complication. CONCLUSIONS: Repeat Amytal testing might detect the loss of sump effect as the AVM is embolized. We conclude that use of data from superselective Amytal tests adds to the safety of AVM embolizations and that repeat Amytal testing potentially could be valuable when serial embolization of a vessel is planned. PMID- 1595468 TI - Dural arteriovenous fistulas of the posterior fossa draining into subarachnoid veins. AB - PURPOSE: To describe the clinical presentation, angioarchitecture, and risks and problems of therapy in patients with dural arteriovenous malformations of the posterior fossa draining into subarachnoid veins. PATIENTS AND METHODS: Twelve patients with dural arteriovenous malformations of the posterior fossa draining into subarachnoid veins were studied. RESULTS: These fistulas often presented with intracranial hemorrhage (eight cases) and myelopathy (two cases). They were located in the tentorium (six cases) or at the skull base (six cases). The arterial supply was provided by branches of the external carotid artery (nine cases), by the posterior meningeal branch of the vertebral artery (nine cases), and by the meningohypophyseal trunk (three cases). The fistulas drained directly into a cortical vein (six cases) or into a venous lake (six cases). In two cases, perimedullary draining veins were observed. The treatment modalities were endovascular embolization alone (two cases), surgery alone (five cases), and embolization followed by surgery (three cases). Despite the treatment, four patients died; in two cases, intracranial hemorrhage recurred. CONCLUSIONS: Subtotal occlusion of a fistula by surgery or embolization alone is not protective against further complications, especially hemorrhage. The goal of treatment is to achieve a rapid and complete anatomical cure; combined endovascular and neurosurgical treatment seems to be the therapeutic choice. PMID- 1595470 TI - Treatment of carotid cavernous fistulas: a new balloon delivery system. PMID- 1595469 TI - Micro-arteriovenous malformations of the brain: superselective angiography in diagnosis and treatment. AB - PURPOSE: We assessed the usefulness of superselective angiography in patients with micro-arteriovenous malformations. PATIENTS AND METHODS: Five patients had superselective angiography for either diagnosis or treatment of brain arteriovenous malformations having a nidus of less than 1 cm. All patients presented with an intracerebral hematoma. RESULTS: In one patient superselective angiography confirmed the presence of a shunt that was suspected due to visualization of an early vein on the follow-up angiogram; in another patient superselective angiography was helpful in defining the topography of the malformation; in the remaining three patients, superselective angiography was used for embolization of the malformation. We were unsuccessful in achieving a complete angiographic cure in these 3; however, superselective angiography revealed an aneurysm in one that was obliterated by the liquid adhesive embolic agent. CONCLUSION: With the recent advances in microcatheters, superselective angiography has a promising role in defining the topography and angioarchitecture of micro-arteriovenous malformations. Micro-arteriovenous malformations may not be angiographically evident at the time of initial hemorrhage due to the hematoma. With future technical advances it may be possible to completely obliterate these malformations by embolization alone. PMID- 1595471 TI - Cerebral arteriovenous malformation causing epistaxis. PMID- 1595472 TI - Experience with high-dose gadolinium MR imaging in the evaluation of brain metastases. AB - PURPOSE: To assess the effectiveness and safety of higher doses of gadoteridol in the MR evaluation of patients with brain metastases. MATERIALS AND METHODS: Thirty-one patients with a clinical suspicion of brain metastases were studied prospectively with gadoteridol, a new, nonionic, low-osmolality contrast agent. Each patient received an initial injection of 0.1 mmol/kg and an additional dose of 0.2 mmol/kg 30 minutes later. Images were obtained before, immediately after, and 10 and 20 minutes after the initial dose. Images also were acquired immediately after the additional dose of gadoteridol. RESULTS: No adverse effects were attributed to the injection of gadoteridol. Four patients' examinations were excluded from analysis because of machine malfunction (two patients) and excessive motion artifact (two patients). Four patients had no detectable metastases. After the additional dose of gadoteridol, there was a marked qualitative improvement in lesion conspicuity and detection. The conspicuity of 80 of 81 lesions was increased in the high-dose studies, and 46 new lesions were detected in 19 of 27 patients. Quantitative image analysis demonstrated a significant increase in normalized mean lesion contrast between the initial-dose and high-dose studies (35 lesions identified in 13 patients, P less than .0001). The additional information gained by high-dose examinations contributed to a potential modification of the treatment in 10 of 27 patients. High-dose examinations increased flow-related artifact in the posterior fossa in 12 of 27 patients. CONCLUSION: Based on our preliminary results, high-dose gadolinium enhanced MR examinations may have advantages over 0.1 mmol/kg examinations in detecting early and/or small metastases. This may be significant in the management of patients with cerebral metastases. PMID- 1595473 TI - Pontine glioma extending to the ipsilateral cavernous sinus and Meckel's cave: MR appearance. AB - The authors describe an exophytic glioma of the pons that grew into the Meckel's cave and cavernous sinus in a 75-year-old man. Pontine gliomas should be included in the differential diagnosis of a hyperintense, complex cystic mass seen along the distribution of cranial nerve V. PMID- 1595474 TI - MR imaging of diffuse glioma. AB - Neuroradiologic diagnosis of "gliomatosis cerebri" is hampered by the diffuse, isodense character of the lesion, and the fact that it may not enhance when intravenous contrast medium is administered. Clinical signs and symptoms are usually nonspecific, nonfocal, and disproportionately mild. We report a case of diffuse glioma in a 30-year-old man, discuss the difficulty in arriving at a precise diagnosis of gliomatosis cerebri, and examine the possible role of MR in its detection and delineation. PMID- 1595475 TI - Origin of the right vertebral artery from the left side of the aortic arch proximal to the origin of the left subclavian artery. PMID- 1595477 TI - Bulbar poliomyelitis: MR findings with pathologic correlation. PMID- 1595476 TI - Sequential cranial MR findings of asymptomatic and neurologically symptomatic HIV+ subjects. AB - PURPOSE: To compare results of a prospective MR and clinical reevaluation of HIV+ asymptomatic and neurologically symptomatic subjects who had had initially abnormal cranial studies to determine what cranial MR changes occur and how these changes correlate with serial neurologic and neuropsychologic findings. PATIENTS AND METHODS: Thirty-one asymptomatic (n = 20) and neurologically symptomatic (n = 11) subjects seropositive for the human immunodeficiency virus (HIV+) were prospectively reevaluated by cranial magnetic resonance (MR) one to two years following an initially abnormal MR of the brain. RESULTS: All 31 HIV+ subjects with initial abnormal MR had abnormal follow-up scans (showing atrophy and/or white matter lesions). Twenty-seven showed no progression of MR abnormalities (among whom were 18 with minimally abnormal scans who remained asymptomatic with improved or static neuropsychologic performance). Of the four subjects with scan changes (all with clinically suspected HIV encephalopathy), one showed MR, clinical, and neuropsychologic test improvement; the remaining three showed MR (n = 3), neurologic (n = 3), neuropsychologic (n = 1) worsening and autopsy (n = 1) confirmed the presence of HIV-1 containing multinucleated giant cells in the brain. CONCLUSIONS: This study suggests that: 1) Progression of intracranial MR abnormalities due to HIV-1 is seen only in a minority of HIV+ subjects over a 1- to 2-year time period, only in those neurologically symptomatic, and correlates with clinical deterioration. 2) Minor cerebral MR abnormalities seen in HIV+ subjects who remain neurologically asymptomatic do not change over a 1- to 2-year period. 3) Although HIV is known to infect the brain early, it may, nevertheless, not routinely do significant anatomical damage early on in the disease, as based on MR criteria. PMID- 1595478 TI - Choroid plexus infections: neuroimaging appearances of four cases. PMID- 1595479 TI - MR imaging of cerebrospinal fluid rhinorrhea after operation for acoustic neurinoma. AB - MR was useful in verifying CSF rhinorrhea following removal of an intracanalicular acoustic neurinoma via the occipital route in a 29-year-old man. MR accurately identified the location of the CSF leak. PMID- 1595480 TI - Morphometric changes of the human midbrain with normal aging: MR and stereologic findings. AB - PURPOSE: To determine the effects of age on estimated midbrain volume. PATIENTS AND METHODS: T2-weighted MR imaging and an unbiased stereologic method were used in 75 volunteers; the subjects ranged in age from 21 to 82 years and were without any significant neurologic or psychiatric disorders. RESULTS: Age was negatively correlated with estimated midbrain volume (R = -.39, P less than .0005), with the anteroposterior diameter through the substantia nigra (R = -.33, P less than .004) and with the interpeduncular distance (R = -.24, P less than .04). The linear measurements for the right and left side were almost identical. These findings are consistent with prior reports of nigrostriatal degeneration with increasing age. Furthermore, they suggest a close symmetry of age-related changes between the right and left side in normal subjects. CONCLUSIONS: Volumetric and linear measurements of midbrain morphology with MR may prove useful in the investigation of neurologic disorders such as Parkinson disease. PMID- 1595481 TI - Partial albinism with immunodeficiency: a rare syndrome with prominent posterior fossa white matter changes. AB - PURPOSE: To describe our experience in infants with partial albinism and immunodeficiency (PAID), a rare, recently recognized, probably autosomal recessive disorder. PATIENTS AND METHODS: Five infants suffering from this disease were examined with CT of the brain and four of these patients also underwent MR. Four of the five children also underwent follow-up CT or MR exams. RESULTS: Three of the patients followed with serial examinations demonstrated a rapid progress of white matter changes together with a loss of brain tissue over a few months. In all four patients subjected to follow-up, the posterior fossa white matter structures were severely involved during the course of the disease. CONCLUSIONS: This syndrome should be added to the list of demyelinating diseases, and should be kept in mind when white matter changes are prominent in the posterior fossa. PMID- 1595482 TI - Cerebral hemodynamics and cerebral blood volume: MR assessment using gadolinium contrast agents and T1-weighted Turbo-FLASH imaging. AB - PURPOSE: To assess the degree and regional pattern of first-pass brain enhancement using dynamic MR imaging. MATERIALS AND METHODS: Ultrafast MR imaging (1.06-second acquisition time per image) was performed in 19 healthy subjects following a bolus IV injection of a gadolinium contrast agent; 36 patients with suspected pathology were studied using the same protocol. RESULTS: Calculated percent blood volumes were 4.9% for right cortical gray matter, 4.8% for left cortical gray matter, and 2.6% for white matter. Subtraction images were obtained that depicted the first pass "blood pool" pattern of enhancement (gray and white matter) which was significant. CONCLUSION: Preliminary evidence suggests utility for cerebral "blood pool" imaging, especially if reduced image acquisition times can be achieved. PMID- 1595483 TI - Late onset familial Hallervorden-Spatz disease: MR findings in two sisters. AB - Two sisters affected by late onset Hallervorden-Spatz disease are described. In both patients, MR showed rings of decreased signal intensity surrounding hyperintense areas that gave a target-like appearance to the globi pallidi, a finding that corresponds with the known pathologic lesions in the disease. MR reflects the metabolic and anatomic evaluation of this disease. PMID- 1595484 TI - Meningeal Gd-DTPA enhancement in multiple sclerosis. PMID- 1595485 TI - Meningeal enhancement in multiple sclerosis truth or coincidence? PMID- 1595486 TI - Creutzfeldt-Jakob disease: focal symmetrical cortical involvement demonstrated by MR imaging. AB - The authors present two biopsy-proved cases of Creutzfeldt-Jakob disease. MR appears to be more sensitive than CT in detecting pathologic changes; signal abnormalities, when found, are predominantly within gray matter and may involve only peripheral cortex. PMID- 1595488 TI - The ventriculofugal arteries. PMID- 1595487 TI - Imaging cerebral blood flow in interventional neuroradiology. PMID- 1595489 TI - The risks of vertebral angiography in vertebrobasilar disease. PMID- 1595490 TI - The wash-in/washout protocol in stable xenon CT cerebral blood flow studies. AB - PURPOSE: We conducted a comparative study to optimize the scanning and inhalation protocols for xenon CT cerebral blood flow (CBF) examination (Xe CT), with the aim of improving the practical performance of Xe CT as a routine clinical examination. MATERIALS AND METHODS: Four different inhalation protocols, including 3-min, 6-min, and 8-min wash-in protocols, and a 3-min wash-in/5-min washout protocol, were compared in five healthy volunteers. Each subject underwent two serial Xe CT examinations with an interval of 30 min between the first one (wash-in) and the second one (wash-in/washout). A computer simulation was also performed to support the results of the clinical study. The rate of success was calculated from our experience of 110 clinical cases examined with the wash-in/washout protocol over the last 9 months. RESULTS: The mean CBF values with 6-min and 8-min wash-in protocols were 59.0 and 59.5 mL/100-g brain per min in the thalamus, and 19.5 and 19.0 mL/100-g brain per min in the frontal white matter, respectively. The mean CBF values with 3-min wash-in/5-min washout protocol were 60.0 mL/100-g brain per min in the thalamus and 18.5 mL/100-g brain per min in the frontal white matter, respectively. Computer simulation showed improved signal-to-noise ratio by employing the 3-min wash-in/5-min washout protocol instead of 8-min wash-in protocol for the same number of data points. The rate of success improved to 99.1% due to the significant decrease in head motion with the shorter period of inhalation. CONCLUSION: A wash-in/washout protocol is a useful alternative in Xe CT CBF measurement and more useful than the wash-in method for clinical purposes. PMID- 1595491 TI - Dyke Award Paper. Kinetics of pathologic blood-brain-barrier permeability in an astrocytic glioma using contrast-enhanced MR. AB - PURPOSE: The feasibility of measuring blood-brain barrier permeability was studied in a 36B-10 brain glioma model in rats. MATERIALS AND METHODS: In stage I of our study, sequential MR images of glioma-implanted rats were obtained following intravenous administration of three contrast agents of different molecular sizes--Gd-DTPA, polylysine-(Gd-DTPA), and albumin-(Gd-DTPA). In a second set of experiments, sequential MR imaging with Gd-DTPA, quantitative measurements of plasma Gd-DTPA concentration, and postmortem tumor Gd-DTPA measurements were used to estimate the blood-to-tissue transport coefficient (Ki) in the rat glioma model at 11 and 15 days postimplantation. RESULTS: In stage I, Gd-DTPA caused rapid and greatest tumor enhancement with a significant washout from the tumor during the 120-min experiment. Tumor enhancement using polylysine (Gd-DTPA) occurred later and was significantly less compared to Gd-DTPA. Tumor signal intensity increased only slowly over time and the peak level of enhancement was least using albumin-(Gd-DTPA). In stage II, the mean (+/- 1 SD) Ki values were 1.1 +/- .24 at 11 days, and 9.3 +/- .8 at 15 days postimplantation. These results correspond well with published data obtained by autoradiography. CONCLUSION: We believe that the differential enhancement pattern using contrast agents of different molecular sizes reflects a differential permeability of the pathologic blood-brain barrier, and that our studies demonstrate the feasibility of using frequent sequential images and a graphical approach to Ki calculation to determine the blood-to-tissue transport coefficient using contrast-enhanced MR. PMID- 1595492 TI - Crossed cerebellar diaschisis and loss of consciousness during temporary balloon occlusion of the internal carotid artery. AB - We encountered a case of crossed cerebellar diaschisis during temporary balloon occlusion of the internal carotid artery in a 59-year-old woman. The rapidity of the diaschisis was unusual and SPECT scanning was adequate to show the early defect. PMID- 1595493 TI - Crossed cerebellar diaschisis: occurrence and resolution demonstrated with PET during carotid temporary balloon occlusion. PMID- 1595495 TI - MR diagnosis of brain death. PMID- 1595494 TI - Crossed cerebellar diaschisis. PMID- 1595496 TI - Cerebral palsy: MR findings in 40 patients. AB - PURPOSE: We used MR to retrospectively analyze the brains of patients suffering from cerebral palsy, our aim being to determine MR's role in the assessment of brain damage and the relationship of pre-, peri-, and post-natal events to cerebral palsy. METHODS: Forty patients (aged 1 month to 41 years) underwent MR scanning and findings were correlated with clinical histories in all cases. RESULTS: Review of MR scans of 11 patients who had been born prematurely revealed findings of periventricular white matter damage, indicative of hypoxic-ischemic brain injury (82%), the chronology of which was difficult to determine. Among 29 patients who had been born at term, three major patterns emerged: (1), gyral anomalies, suggestive of polymicrogyria, consistent with mid-second trimester injury; (2), isolated periventricular leukomalacia reflecting late second- or early third-trimester injury; and (3), watershed cortical or deep gray nuclear damage, consistent with late third-trimester, perinatal or postnatal injury. In 16 (55%) of 29 patients born at term, MR findings of intrauterine brain damage were observed; in over half of these cases MR revealed developmental anomalies, which is nearly twice the rate reported in prior studies employing CT. CONCLUSIONS: Our results support a growing consensus that cerebral palsy in term infants is often the result of prenatal factors, and less commonly related to the perinatal period. PMID- 1595497 TI - Value of MR in definition of the neuropathology of cerebral palsy in vivo. PMID- 1595499 TI - Dr. Morris's Balkan genes. PMID- 1595498 TI - Schizencephaly: correlation of clinical findings with MR characteristics. AB - PURPOSE: To correlate clinical outcome with the size and location of clefts in patients with schizencephaly. PATIENTS AND METHODS: MR scans and clinical records of 20 patients with schizencephaly were retrospectively reviewed. Seven patients had bilateral clefts (10 open lip clefts, 4 closed lip clefts), eight patients had right-sided unilateral clefts (5 open lip clefts, 3 closed lip clefts), and five patients had left-sided unilateral clefts (3 open lip clefts, 2 closed lip clefts). RESULTS: Statistically significant correlations were found as follows: Patients with bilateral schizencephalies had significantly worse intellectual (P = .004) and speech (P = .03) development than those with unilateral clefts; patients with unilateral large or medium open lip schizencephalies had significantly worse motor (P = .003) and intellectual (P = .008) impairment than those with unilateral closed lip or small open-lip schizencephalies; patients with frontal lobe involvement had a significantly higher incidence of motor dysfunction than those without frontal lobe involvement (P = .01). Strong similarities were noted in the patient outcomes and the locations of cortical anomalies of patients with schizencephaly and those with nonschizencephaly focal cortical dysplasias. CONCLUSION: A common pathogenetic origin for the formation of focal cortical dysplasia in the form of polymicrogyria and schizencephalies is proposed. Patients with small unilateral schizencephalies have a good developmental prognosis, particularly when the motor cortex is not involved. PMID- 1595500 TI - Self-medication in physicians. PMID- 1595501 TI - Product, process and medicine. PMID- 1595502 TI - Equanimity. PMID- 1595503 TI - Sonography in the diagnosis of acute appendicitis. PMID- 1595504 TI - Tax breaks for physicians providing free medical care. PMID- 1595505 TI - Fireworks: advice for a safer Fourth of July. PMID- 1595506 TI - Sports and prescription eye wear. PMID- 1595507 TI - Rural health and family medicine. PMID- 1595508 TI - Diary from a week in practice. PMID- 1595509 TI - How to extract an indwelling fishhook. AB - Fishhook injuries are fairly common in some geographic areas. Radiography assists in identifying the type of hook and determining its orientation. Two simple techniques can be employed to remove a fishhook safely and easily. PMID- 1595510 TI - Transdermal nicotine replacement and smoking cessation. AB - Transdermal nicotine systems are a useful adjunct to smoking cessation. The larger-sized nicotine patches provide steady-state replacement of approximately 50 percent of the average serum nicotine level obtained by smoking one to one and one-half packs of cigarettes a day. This level is sufficient to prevent many symptoms of nicotine withdrawal, including physical craving, irritability, anxiety, restlessness, hostility, hunger and difficulty concentrating. In double blind, placebo-controlled trials, transdermal nicotine systems have been about twice as successful as placebo in helping patients stop smoking. PMID- 1595511 TI - Aortoenteric fistula. AB - Aortoenteric fistula is a rare but deadly medical emergency. Primary fistulas occur between the native aorta and the intestinal tract. Secondary fistulas occur between an aortic graft and the gastrointestinal tract. Patients often present with a "herald bleed," followed by massive gastrointestinal hemorrhage. Sepsis and abdominal pain in a patient who has had an aortic graft may also indicate the formation of a fistula. Prompt intervention is imperative; the mortality rate is 100 percent if the condition is left untreated. In clinically stable patients with a herald bleed, evaluation usually consists of endoscopy in an operating room. Computed tomographic scanning is useful for patients with signs of sepsis; scans showing an aortic graft surrounded by inflammation and abscess formation may indicate fistula formation. Clinically unstable patients require immediate laparotomy. Even in surgically treated patients, the mortality rate is approximately 60 percent. PMID- 1595513 TI - Intensive insulin therapy: Part II. Multicomponent insulin regimens. AB - In patients with insulin-dependent diabetes mellitus, insulin is an absolute requirement for life. Once-daily insulin administration is not sufficient to maintain physiologic insulin delivery. Twice-daily delivery of a combination of intermediate-acting and regular insulin may be effective but may limit lifestyle flexibility. Other popular regimens include three daily injections (with a bedtime dose of intermediate-acting insulin) and use of a combination of ultralente and regular insulin. Continuous subcutaneous insulin infusion is another option for patients with insulin-dependent diabetes. In patients with noninsulin-dependent diabetes who require insulin, control can often be achieved with a single daily injection. Recently, the use of bedtime NPH or ultralente insulin has been emphasized for control of moderate hyperglycemia in these patients. For patients with severe hyperglycemia, insulin administration is similar to that for patients with insulin-dependent diabetes. The use of combination therapy with insulin and sulfonylurea for noninsulin-dependent diabetes is controversial. PMID- 1595512 TI - Initial management of pediatric head trauma. AB - Head injuries are the most common cause of disability and death in children. Identification of children who require specialized management following a head injury will reduce the associated morbidity and mortality. Thus, it is important to differentiate the child who can be safely observed and who will recover spontaneously from the child who will develop a progressive neurologic deficit from a treatable cause. A thorough history, a tailored neurologic examination and limited radiographic studies will assist the family physician in making this determination. PMID- 1595514 TI - Primary tracheal neoplasms: recognition, diagnosis and evaluation. AB - Primary neoplasms of the trachea are much less common than malignancies of the larynx and lungs. Tracheal neoplasms account for less than 0.1 percent of all neoplasms. Their importance lies in the fact that they may initially be misdiagnosed, resulting in a delay in diagnosis ranging from months to years. The most common benign tracheal neoplasms are hemangiomas, squamous papillomas and fibromas. The most common tracheal malignancy is squamous cell carcinoma. Symptoms of these lesions are usually related to airway obstruction and include wheezing, dyspnea and cough. PMID- 1595515 TI - Retinal vein occlusion. AB - Retinal vein occlusion is a common form of retinal vascular disease, especially in middle-aged and older individuals. The diagnosis is based on the funduscopic finding of retinal vein dilatation in association with retinal hemorrhages and cotton-wool spots. The pathology can involve the entire venous system or can be limited to a branch of the central retinal vein. Retinal vein occlusion can be distinguished clinically from diabetic retinopathy and other retinal diseases. Treatment for the acute phase of retinal vein occlusion has been disappointing. However, some late complications, such as persistent macular edema and neovascularization of the iris and retina, respond well to retinal photocoagulation. The family physician has an important role in detecting and controlling risk factors for retinal vein occlusion, including hypertension, diabetes mellitus and hyperviscosity syndromes. PMID- 1595516 TI - Pruritus. AB - Pruritus is an important sign of localized or systemic disease and sometimes may be the only symptom of potentially fatal illness. Localized causes of pruritus include stasis dermatitis, atopic dermatitis, contact dermatitis, neurodermatitis and scabies. Generalized pruritus may be caused by environmental factors such as low humidity, skin diseases such as urticaria, or internal diseases such as biliary obstruction, renal failure, hematologic malignancy or acquired immunodeficiency syndrome. Therapy for pruritus depends on identification and treatment of the underlying cause. If no specific etiology is found, therapy is palliative. Avoidance of frequent bathing may be helpful, especially when xerosis plays a role. Topical emollients or short-term therapy with low-potency steroids may also be effective. Oral antihistamines provide nonspecific relief for many patients with intractable pruritus. PMID- 1595517 TI - Common infections in the elderly. AB - Symptoms of infection in the elderly may be absent, vague or atypical. Infection should be suspected when an elderly patient presents with a decline in well-being or with non-specific symptoms such as falls, dizziness, confusion, anorexia or weakness. Common infections include bacterial pneumonia, urinary tract infection, intra-abdominal infections, gram-negative bacteremia and infection of decubitus ulcers. Antibiotic therapy is not recommended for asymptomatic bacteriuria or locally infected decubitus ulcers. Drug dosages should be adjusted for the age associated decline in renal function and for hepatic or renal insufficiency. The trend in antibiotic therapy is evolving toward the use of third-generation cephalosporins instead of aminoglycosides to avoid the side effects of nephrotoxicity and ototoxicity. Pneumococcal, influenza and tetanus/diphtheria immunizations help prevent morbidity and mortality. PMID- 1595518 TI - Principles of drug therapy in geriatric patients. AB - The elderly comprise 12 percent of the U.S. population but consume 33 percent of all prescription drugs. The incidence of adverse drug reactions is significantly higher in persons over age 65 than in younger population groups. The increased risk of adverse drug effects is related to decreased organ reserve capacity, to altered pharmacokinetics and pharmacodynamics, and to polypharmacy with associated drug-drug and drug-disease interactions. An organized therapeutic plan and critical evaluation of the list of drugs an elderly patient is taking will help in establishing a safe and effective drug regimen. PMID- 1595519 TI - Medication errors. PMID- 1595520 TI - AAFP position statement on access to health care. PMID- 1595521 TI - Effects of trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty. AB - Trapidil (triazolopyrimidine), a platelet-derived growth factor antagonist, is a potential inhibitor of intimal proliferation after percutaneous transluminal coronary angioplasty (PTCA). To study its efficacy, 72 patients were randomized to receive Trapidil (600 mg/day orally for 1 week before PTCA and for 4 to 6 months after PTCA; n = 36) or aspirin and dipyridamole (aspirin, 300 mg/day, and dipyridamole, 150 mg/day; n = 36). At entry, both groups were comparable with regard to age, sex, dilated vessels, severity of pre-PTCA stenosis, residual stenosis after PTCA, and prevalence of coronary risk factors. Repeat coronary angiography was performed 6 months after PTCA. Restenosis, defined as the loss of at least 50% of the gain in luminal diameter accomplished by dilation, was present in seven patients (19.4%) in the trapidil group and 15 patients (41.7%) in the aspirin-dipyridamole group (p less than 0.05). The progression of stenosis in patients with less than 30% residual stenosis was significant in both groups. Furthermore, in the patients with residual stenosis of more than 30%, progression of stenosis was less in the trapidil group than in the aspirin-dipyridamole group. Thus trapidil was useful in preventing intimal proliferation after PTCA, especially in patients with more than 30% residual stenosis after PTCA. PMID- 1595522 TI - The relationship of anticoagulation level and complications after successful percutaneous transluminal coronary angioplasty. AB - The degree of anticoagulation and its effect on the frequency of abrupt coronary artery closure, coronary ischemia, bleeding complications requiring transfusion, and death were examined in 336 patients after elective percutaneous transluminal coronary angioplasty (PTCA). All patients received a bolus of 10,000 U of heparin at the beginning of the procedure followed by a continuous infusion of 2000 U/hr. At the conclusion of the procedure the infusion was reduced to 1000 U/hr and continued for 18 to 24 hours at which time the heparin infusion was suspended to allow removal of arterial and venous access sheaths. Partial thromboplastin time (PTT) was examined while patients continued to receive the heparin infusion. There was a variable degree of PTT prolongation in response to a standard dose of heparin with a range of 34 seconds to "greater than 150 seconds." Patients were divided into two groups according to the degree of heparin-induced PTT prolongation: group A included 271 patients with PTT greater than or equal to 3 times the control value, and group B comprised 65 patients with PTT less than 3 times the control value. Ischemic complications were analyzed on day 1 after PTCA and at hospital discharge. Bleeding complications and mortality were examined only at hospital discharge. There was a significant reduction in the incidence of abrupt coronary artery closure in group A on day 1 (1.5% vs 10.7%, p less than 0.001) and at hospital discharge (2.6% vs 10.7%, p less than 0.003).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595523 TI - Relationship between the preexistent coronary collateral circulation and successful intracoronary thrombolysis for acute myocardial infarction. AB - The purpose of this study was to evaluate whether the existence of coronary collateral circulation influences recanalization rates of intracoronary thrombolysis. The study population consisted of 85 consecutive patients undergoing intracoronary thrombolysis within 6 hours after the onset of the first acute myocardial infarction, all of whom had a complete occlusion of the infarct related coronary artery. Intracoronary thrombolysis with high-dose urokinase (960,000 IU) was attempted at a rate of 24,000 IU/min. Of 18 patients (group A) who had good angiographic collateral circulation to the area perfused by the infarct-related coronary artery, the obstructed artery was recanalized to a residual luminal diameter stenosis of less than or equal to 90% (successful recanalization) in only five (28%). In contrast, of 67 patients (group B) with poor or no collateral circulation, recanalization was successful in 40 (60%) (p less than 0.05). Antegrade flow of infarct-related arteries was observed following thrombolysis in 12 (67%) of 18 group A patients and in 56 (84%) of 67 group B patients (p = NS). It was concluded that (1) the presence of collaterals correlates with the presence of high-grade stenosis; (2) the presence of collaterals correlates with the presence of high-grade stenosis; (2) the presence of collaterals is inversely related to the efficacy of thrombolytic therapy; and (3) the difference in successful recanalization rates observed between the two groups probably reflects the impact of underlying stenosis severity on the effectiveness of lytic therapy. PMID- 1595524 TI - Ischemic expansion during acute myocardial infarction and reversal by coronary reperfusion. AB - Previous studies have shown that infarct expansion occurs at least 1 day after a large transmural infarction. To assess whether regional left ventricular expansion is evident within hours of an acute myocardial infarction, 25 adult mongrel dogs underwent left circumflex coronary artery occlusion for 2 hours and 22 of these were subsequently reperfused. Two-dimensional echocardiography was used to record left ventricular topography and function at baseline, at 2 hours of occlusion, and following reperfusion. Short-axis midpapillary echocardiograms were analyzed using a microcomputer digitizing routine by establishing a 360 degree circumferential map of the left ventricle. The central ischemic zone was defined as that region with the most depressed contractility after 2 hours of occlusion, and the normal zone was set at 180 degree away from the central ischemic zone. Endocardial and epicardial segment lengths and wall thickness were measured for both the normal zone and the central ischemic zone at end diastole. After 2 hours of occlusion, diastolic central ischemic endocardial (1.3 +/- 0.05 to 1.42 +/- 0.04 cm, p less than 0.01) and central ischemic epicardial (1.84 +/- 0.06 to 1.93 +/- 0.06 cm, p less than 0.05) segment lengths were significantly increased. There were no significant changes in segment lengths or wall thickness in the normal zone. After 2 hours of occlusion, there was significant diastolic left ventricular (LV) dilatation (LV area increased from 18.2 +/- 1.3 to 21.0 +/- 1.3 cm2, p less than 0.01). Furthermore, central ischemic endocardial and epicardial segment length changes from baseline to occlusion correlated significantly with LV dilatation (r = 0.56, p less than 0.003; r = 0.55, p less than 0.004 respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595525 TI - Activated neutrophils aggravate endothelial dysfunction after reperfusion of the ischemic feline myocardium. AB - Endothelial dysfunction, as evidenced by decreased stimulated release of endothelium-derived relaxing factor (EDRF), occurs after reperfusion of the ischemic myocardium. To better understand this endothelial dysfunction, isolated cat hearts were perfused under constant flow by the Langendorff procedure with Krebs-Henseleit solution devoid of blood cells. Following global ischemia (90 minutes) and reperfusion (20 minutes), coronary vasorelaxation to the endothelium dependent vasodilator acetylcholine (ACh) was 70 +/- 3% of initial values (p less than 0.01) compared with 90 +/- 4% in nonischemic control perfused hearts. No decrement occurred in response to the endothelium-independent vasodilator nitroglycerin (NTG). Coronary artery rings isolated from the ischemic left circumflex coronary artery showed a similar degree of endothelial dysfunction to ACh, with normal relaxation in response to NaNO2. Autologous cat neutrophils (100 million cells), activated with 100 nmol/L f-met-leu-phe infused into the heart directly before and throughout reperfusion, resulted in a further decrement in ACh-induced vasodilation, to 55 +/- 5% of initial response, with no effect on NTG induced vasodilation. Similar results were obtained with coronary artery rings isolated from perfused cat hearts and exposed to neutrophils. This neutrophil enhanced endothelial dysfunction was inhibited by human superoxide dismutase as well as by an antibody to the adherence glycoprotein complex CD-18 (i.e., MAbR 15.7). Therefore endothelial dysfunction occurs initially upon reperfusion of the previously ischemic heart and is aggravated by superoxide radicals produced by activated neutrophils. PMID- 1595526 TI - The prognostic significance of angina pectoris preceding the occurrence of a first acute myocardial infarction in 4166 consecutive hospitalized patients. AB - We examined the role of chronic (greater than 1 month) angina pectoris (AP) before acute myocardial infarction (AMI) in predicting hospital and long-term mortality rates among 4166 patients with first AMIs. The prevalence of AP in these patients was 43%. Chronic AP was more common in women (49%), patients with hypertension (49%), and diabetic patients (49%) than in men and counterparts free of the former conditions (p less than 0.005). In patients with AP the hospital course was more complicated and non-Q-wave AMI was more common than in counterparts without AP. In-hospital (16%), as well as 1 (8%)- and 5-year postdischarge (26%), mortality rates in hospital survivors were higher among patients with previous AP than in patients without previous AP (12%, 6%, and 19%, respectively) (p less than 0.01). After adjustment for age and all other predictors of increased hospital mortality rates in this cohort of patients, AP preceding AMI emerged as an independent predictor of increased hospital mortality rates (odds ratio 1.30; 90% confidence interval 1.10 to 1.53). For postdischarge mortality rates (mean follow-up 5 1/2 years), the covariate-adjusted relative risk of death in patients with AP was similar at 1.29 (p less than 0.0001; 90% confidence interval 1.16 to 1.44), according to estimation by Cox proportional hazards model. These data support the notion that preexisting AP identifies a group of patients at increased risk of death. PMID- 1595528 TI - Left ventricular regional dysfunction induced by intracoronary papaverine in patients with isolated stenosis of the left anterior descending coronary artery. AB - Intracoronary papaverine was administered to eight subjects with normal coronary arteries and to nine patients with single-vessel disease of the left anterior descending coronary artery. All patients had normal left ventricular function at baseline. After papaverine, global and regional ventricular function were unchanged in the normal group. In patients with left anterior descending coronary artery stenosis, intracoronary papaverine resulted in significant wall motion abnormalities and decrease of ejection fraction (from 65 +/- 6% to 54 +/- 9%, p less than 0.01). A full spectrum of responses was observed, however, in these patients, some having almost no change of regional wall motion while others had large anterior dyskinesis. No relationship was found between the severity of the stenosis and the amount of regional dysfunction induced by intracoronary papaverine. These data demonstrate the lack of relationship between the angiographic severity of a stenosis and its impact on left ventricular segmental contraction. This suggests that techniques aimed at producing wall motion abnormalities by means of coronary anterior vasodilation may not be recommended as first-line strategy for the detection of patients with coronary artery disease. PMID- 1595527 TI - Coronary tandem lesions: effect of exercise. AB - Coronary vasomotion of two stenoses in series (i.e., tandem lesion) was studied in 10 patients with coronary artery disease. Percent area stenosis was 69% +/- 23% for the first (S1) lesion and 70% +/- 37% for the second (S2). Quantitative coronary arteriography was carried out at rest, during two levels of exercise (2 minutes, 75 W and 1.9 minutes, 100 W), and at 5 minutes after sublingual administration of 1.6 mg nitroglycerin. Both stenoses showed exercise-induced vasoconstriction (S1: -29%, p less than 0.01 versus rest; S2: -29%, p less than 0.01 versus rest), which was reversible after sublingual administration of nitroglycerin (S1: +15%, not significant versus rest; S2: +13%, not significant versus rest). The vessel segment between the two stenoses showed no vasomotion during exercise, whereas the pre- and poststenotic "normal" vessel segment elicited exercise-induced vasodilation. There was an inverse relationship between percent area stenosis of the second lesion and exercise-induced vasoconstriction of the first lesion (correlation coefficient = 0.84). The more severe the distal stenosis was, the less exercise-induced stenosis narrowing of the proximal lesion was observed. Thus it is concluded that coronary vasomotion of two stenoses in series is dependent on both active and passive mechanisms because both lesions show exercise-induced vasoconstriction, but vasomotion of the proximal lesion is dependent on the severity of the second one. PMID- 1595529 TI - Evaluation of a personal computer-based quantitative coronary analysis system for rapid assessment of coronary stenoses. AB - Quantitative coronary analysis (QCA) is a technique that is rarely used because of the complexity and expense of existing systems. We studied a new personal computer-based QCA system that is capable of both geometric and densitometric analysis and compared it to a previously validated QCA system. Both systems performed extremely well in phantom analysis with 11 phantoms filmed in both 5 inch and 7-inch magnifications (R greater than 0.97 and SEE less than 0.33 mm for all modes). In 28 abnormal coronary angiograms analyzed at end diastole, stenosis and reference diameter correlations between the two systems were excellent (R = 0.90 and 0.96 and SEE = 0.43 and 0.33 mm for densitometric and geometric modes, respectively). Intraobserver and interobserver correlation was also excellent for both analysis modes. The new QCA system was able to perform analysis in approximately one third the time required by previously validated system and was much less expensive. We conclude that personal computer-based coronary analysis is an accurate, quick, and relatively inexpensive means for performing QCA that may help to make this technique feasible for nonresearch settings. PMID- 1595530 TI - The incidence of cardiac events in Japanese men with atypical or nonanginal chest pain: a prospective study on the significance of exercise testing. AB - The incidence of cardiac events in Japanese men (mean age 54 +/- 10 years) with atypical or nonanginal chest pain was assessed prospectively. Three groups of patients, those with typical angina (TA; n = 134), those with atypical angina (AA; n = 192), and those with nonanginal chest pain (NA; n = 311) were studied with regard to cardiac events (cardiac death or nonfatal myocardial infarction), risk factors, and results of exercise testing. The total cholesterol and high density lipoprotein-cholesterol levels were significantly different among the three groups, but no differences were observed for other risk factors. The incidences of cardiac events were 8.5%, 2.2%, and 1.3% in the TA, AA, and NA groups, respectively (p less than 0.05) during 3.2 +/- 1.5 years. Significant ST segment changes were observed in 70.1%, 25.5%, and 18.0% of the patients in the TA, AA, and NA groups, respectively, at the time of enrollment. The risk ratio for cardiac events in a positive exercise test was 1.7 (difference not significant) for the TA group and 6.1 (p less than 0.05) for the others combined (AA and NA groups). The risk ratio adjusted for risk factors (Cox model) was 2.2 (difference not significant) for the TA group and 4.9 (p less than 0.05) for the AA and NA groups combined. In conclusion, the incidence of cardiac events in those with AA or NA chest pain was relatively low in Japan, but the independent prognostic significance of positive exercise testing was demonstrated in this group of patients. PMID- 1595531 TI - Circadian variation of spectral indices of heart rate variability after myocardial infarction. AB - The circadian variations of spectral indices of heart rate variability were analyzed in 20 patients 4 weeks after a first and uncomplicated myocardial infarction (MI) and in 20 control subjects. R-R interval and variance showed a characteristic day-night pattern with a significant reduction of the latter parameter in patients after MI (10,967 +/- 1109 msec2 vs 16,860 +/- 2132 msec2). Control subjects were characterized by a predominance of low-frequency (approximately 0.1 Hz) component during the day and of high-frequency (approximately 0.25 Hz) component during the night, which reflected the expected 24-hour pattern of variation of sympatho-vagal balance. A 24-hour elevation (64 +/- 3 normalized units [nu] vs 56 +/- 2 nu; p less than 0.05) of the low frequency component and a smaller (23 +/- 2 nu vs 32 +/- 2 nu; p less than 0.05) high-frequency component during the night differentiated patients after MI from subjects. The difference between the two groups was even more evident when the 24 hour sympatho-vagal balance was assessed with the low frequency/high frequency ratio. Thus spectral analysis of heart rate variability indicates that in patients after MI there is an alteration of neural control mechanisms as indicated by the presence of signs of sympathetic activation and by the attenuation of the nocturnal increase in vagal tone. PMID- 1595532 TI - Electrical cardioversion after amiodarone administration. AB - The possible effect of amiodarone administration on the effectiveness and complications of electrical cardioversion of supraventricular tachyarrhythmias has not been properly assessed. To investigate the effects of amiodarone on cardioversion, we performed 130 electrical cardioversion procedures in 116 patients who were receiving long-term amiodarone therapy (group I) and 44 cardioversion procedures in 43 patients who were receiving intravenous infusions of amiodarone (group II). All patients in groups I and II had atrial fibrillation or flutter. In group I, there was a higher incidence of ventricular premature beats than in a control group of patients who underwent 100 cardioversions; one patient had severe bradycardia with asystole, which was resolved satisfactorily. In group II there was a higher incidence of sinus bradycardia and ventricular premature beats. It was concluded that electrical cardioversion of supraventricular arrhythmias can be safely performed in patients who are receiving long-term oral or intravenous amiodarone therapy if the usual precautions are observed. PMID- 1595533 TI - Adenosine versus verapamil in the treatment of supraventricular tachycardia: a randomized double-crossover trial. AB - The safety and efficacy of verapamil and adenosine in the acute termination of supraventricular tachycardia were compared in a randomized double-crossover trial. Of 32 eligible patients with either spontaneous or induced narrow complex tachycardia, seven (22%) patients experienced conversion to sinus rhythm with carotid sinus massage. The other 25 patients were randomly assigned to receive either adenosine (n = 14) or verapamil (n = 11). Relative drug efficacies were 100% for adenosine versus 73% for verapamil, p = NS. Adenosine given at less than or equal to 120 micrograms/kg caused conversion in 12 (86%) of 14 patients. The other two patients required 20 mg adenosine for conversion. After conversion the systolic blood pressure increased significantly in the adenosine group but not in the verapamil group. Reinitiation of tachycardia occurred in two (14%) of 14 patients randomized to the adenosine group. Serious adverse hemodynamic effects were observed in one (9%) of 11 patients randomized to verapamil. The incidence of conversion arrhythmias was similar in both treatment groups (adenosine 57%, verapamil 50%, p = NS). PMID- 1595534 TI - Serial pulmonary function tests in patients treated with low-dose amiodarone. AB - Problems with pulmonary toxicity have emerged as a potentially limiting factor for amiodarone use. We studied 24 consecutive patients receiving low-dose (i.e., less than or equal to 400 mg/day) amiodarone for refractory tachyarrhythmias. Serial pulmonary function test results were correlated with daily dose, serum concentration, cumulated dose, and duration of amiodarone treatment to determine the effect of the drug on pulmonary function. The mean follow-up period for the 24 patients, who completed baseline and follow-up evaluations, was 47 months (range 31 to 75 months). In 22 of the 24 patients a reduction in total diffusion capacity (TLCO) was noted after treatment; for all 24 patients the mean reduction in TLCO was 12.9% of the predicted value (SD 9.6% predicted) (p less than 0.02). The decrease in TLCO was found to be significantly related to an increasing cumulated dose of amiodarone (p = 0.007), whereas the reduction in TLCO was found to be unrelated to sex, age, underlying heart disease, arrhythmia, daily dose of amiodarone, duration of treatment, plasma concentration of amiodarone and desethylamiodarone, and pretreatment pulmonary function abnormalities. Seven (29%) of the patients had asymptomatic pulmonary toxicity with a decrease in TLCO greater than or equal to 20% of the predicted value. In conclusion, long-term treatment with low-dose amiodarone was associated with a substantial decrease in TLCO, a higher cumulative dose of the drug was related to an increasing reduction in TLCO, and pretreatment pulmonary function abnormalities were not predictive for development of subclinical pulmonary toxicity. PMID- 1595535 TI - Dietary lipid modulation of ventricular fibrillation threshold in the marmoset monkey. AB - Programmed electrical stimulation was used to examine the ability of long-term dietary lipid modulation to influence myocardial vulnerability to the induction of ventricular fibrillation in adult marmoset monkeys (Callithrix jacchus). Marmosets fed diets supplemented (to a total of 28.5% of the energy as fat) with polyunsaturated fatty acid (PUFA)-rich tuna fish oil or sunflower seed oil had significantly elevated mean ventricular fibrillation threshold compared with those fed a saturated animal fat supplemented diet or a reference diet not supplemented with fat (11.2% of the energy as fat). Fibrillation threshold was reduced during acute myocardial ischemia induced by coronary artery occlusion but still remained higher in the PUFA-fed animals than either the control or the ischemic threshold in reference or saturated fat supplemented animals. Dietary tuna fish oil was associated with a low incidence of sustained fibrillation episodes and no fatalities. These results indicate that myocardial substrate vulnerability to arrhythmic stimuli is increased during ischemia in a nonhuman primate model but dietary PUFA can reduce vulnerability under both normal and ischemic conditions. Reduced dietary fat intake alone was without effect. PMID- 1595536 TI - Effect of atrioventricular synchrony on stroke volume during ventricular tachycardia in man. AB - The hemodynamic consequences of atrioventricular (AV) synchrony during ventricular tachycardia were evaluated during cardiac electrophysiologic testing. The relationship between stroke volume and the AV interval was investigated on a beat-by-beat basis in six patients during induced monomorphic ventricular tachycardia. Stroke volume was calculated either (1) in the right ventricle using impedance catheter method (four patients) or (2) in the left ventricle using Doppler measurement of aortic blood velocity (two patients). The impedance catheter method underestimated stroke volume by a factor of 4.2 +/- 2.4 compared with the thermodilution cardiac output method. However, there was a highly linear relationship between both methods for computing stroke volume (r greater than 0.9). Five patients had complete AV dissociation during ventricular tachycardia, and different AV intervals spanned the entire tachycardia cycle lengths. Largest stroke volumes were associated with optimal AV intervals within 120 and 230 msec, resulting in a 97 +/- 59% increase in stroke volume over ventricular tachycardia cycles not associated with atrial activity. Customized atrial pacing during ventricular tachycardia may provide a valuable means for artificially establishing the hemodynamically optimal AV interval and eliminating the ventricular tachycardia cycles not preceded by atrial activity. PMID- 1595537 TI - Atrioventricular block during adenosine thallium imaging. AB - Transient atrioventricular (AV) block has been reported during adenosine thallium imaging. This study examined the predictors and hemodynamic implications in 55 patients who had second- or third-degree AV block (group 1) and compared the results with those in 803 patients who did not have AV block (group 2). There were no significant differences in age, sex, or heart rate at baseline between the two groups. ST segment depression was observed in 25% of patients in group 1 and 16% in group 2 (p = NS). Chest pain occurred in 56% in group 1 and 44% in group 2 (p = NS). Preexisting conduction abnormalities (17% vs 16%) and treatment with digitalis (15% vs 15%) and beta-blockers (31% vs 36%) were similar in the two groups. The results of thallium imaging were abnormal in 66% in group 1 and 67% in group 2 (p = NS). Reversible thallium defects were seen in 51% in group 1 and 52% in group 2 (p = NS). The AV block appeared during the first 2 minutes of infusion in 40 patients (73%) and disappeared despite continuation of infusion in 43 (78%). The heart rate during AV block was 79 +/- 18 beats/min, and the systolic blood pressure was 127 +/- 27 mm Hg. Premature termination of adenosine infusion was required in one patient (2%). Aminophylline was used in 5% in group 1 and 2% in group 2 (p = NS). Thus AV block is transient, occurs during the early minutes of infusion, is not aggravated by digitalis or beta-blocker therapy, can be seen in patients with normal perfusion images, and is often well tolerated. PMID- 1595538 TI - Thrombolytic therapy for prosthetic valve thrombosis: a study based on serial Doppler echocardiographic evaluation. AB - Sixteen patients with echocardiographic and cinefluoroscopic evidence of Bjork Shiley prosthetic valve obstruction (13 mitral valves and 3 aortic valves) were treated with intravenous streptokinase. Streptokinase was administered as an initial bolus of 250,000 units for 30 minutes, followed by an infusion of 100,000 units/hr. Serial cinefluoroscopy and echocardiography (M-mode, two-dimensional, and Doppler) were performed at 0, 24, 48, and 72 hours of treatment. The end point of treatment was defined as near normalization of clinical, echocardiographic, and fluoroscopic parameters. Successful thrombolysis was achieved in all patients. The average duration of streptokinase therapy was 43 hours (range 2 to 72 hours). Two of 16 patients had minor systemic embolism during therapy. Short-term follow-up has shown sustained benefit in 14 of 16 patients. Two patients have had rethrombosis of the mitral prosthetic valves and have undergone thrombectomy. Our study demonstrates the feasibility, safety, and efficacy of thrombolytic therapy in the treatment of prosthetic valve thrombosis. It also emphasizes the role of serial Doppler echocardiography in guiding the duration of therapy and assessing its efficacy. PMID- 1595539 TI - Comparison between single (Inoue) and double balloon mitral valvuloplasty: immediate and short-term results. AB - This study compared the results in 60 consecutive patients with severe rheumatic mitral stenosis, who underwent percutaneous double-balloon mitral valvuloplasty by means of a combination of 20 mm + 20 mm diameter balloon catheters (group A), with a similar group of 60 consecutive patients who underwent single (Inoue) balloon mitral valvuloplasty (group B). After balloon mitral valvuloplasty the hemodynamic measurements showed significant improvement in both groups: in groups A and B, respectively, mitral valve area calculated with the Gorlin formula increased from 0.9 +/- 0.2 to 2.1 +/- 0.5 cm2 (p less than 0.001) and from 0.8 +/ 0.2 to 1.9 +/- 0.4 cm2 (p less than 0.001). There was a significant improvement in cardiac functional status in both groups. There was no significant difference between the groups with regard to clinical or hemodynamic improvement, technical failure rate, inadequacy of dilatation, or complications. However, the double balloon technique was more complex and involved a longer screening time--group A, 40 +/- 12 minutes; group B, 21 +/- 10 minutes (p less than 0.001). In our institution the disposable supplies used for the Inoue balloon technique were 40% more expensive than those used for the double-balloon technique. PMID- 1595540 TI - Clinical profile and outcome of restrictive cardiomyopathy in children. AB - The clinical profile and outcome of idiopathic restrictive cardiomyopathy in a group of eight children are reviewed. There were six girls and two boys. Age at presentation was 4.0 +/- 2.6 years (range 1.3 to 9.5 years). All patients had evidence of congestive heart failure with systemic venous congestion. Right or left atrial enlargement was the most consistent ECG finding and was present in all patients. Left ventricular shortening fraction was normal in five patients, increased in two, and mildly reduced in one. The most striking echocardiographic feature was severe biatrial dilatation in the presence of normal or near-normal ventricular cavity dimensions. Marked elevation of left ventricular end-diastolic pressure was noted in all seven patients undergoing cardiac catheterization (34 +/- 7 torr; range 24 to 40 torr). Right ventricular end-diastolic pressure was elevated but significantly different from left ventricular pressure (18 +/- 7 torr; p less than 0.01). A characteristic early diastolic dip with a rapid rise to an elevated plateau (square root sign) was present in five of seven patients. Median survival was 1.4 years. Six patients died 0.2 to 7.0 years after they were initially seen. The actuarial survival rate 1.5 years after presentation was 44%, decreasing to 29% at 4 years. Restrictive cardiomyopathy has a worse prognosis in children than in adults. In part this may reflect the more advanced symptoms of congestive failure at initial presentation. Pediatric patients should be considered for early cardiac transplantation. PMID- 1595541 TI - Increased stiffness and persistent narrowing of the aorta after successful repair of coarctation of the aorta: relationship to left ventricular mass and blood pressure at rest and with exercise. AB - Fifteen children and adolescents who had repair of coarctation of the aorta before age 15, who were not hypertensive at rest, and who had resting arm-leg blood pressure gradients of less than 20 mm Hg underwent noninvasive evaluation of left ventricular structure and function, aortic stiffness, and residual coarctation as well as bicycle exercise testing. These results were compared with those in 15 age- and sex-matched control subjects. The mean resting age-related systolic blood pressure percentiles (63% versus 46%), transverse aortic stiffness measured by the elastic modulus (Ep) (42.1 versus 23.2 kPa), stiffness index beta (beta) (3.66 versus 2.17), echocardiographic left ventricular fractional shortening (0.42 versus 0.36), left ventricular mass index (99.3 versus 81.0 gm/m2), maximum exercise right arm systolic blood pressure (173 versus 156 mm Hg), and exercise arm-leg blood pressure gradient (35 versus 6 mm Hg) were significantly increased in the coarctectomy patients compared with controls. Univariate correlations in the coarctectomy group showed significant relationships of residual aortic narrowing with left ventricular mass index (r = 0.68, p less than 0.01) and resting systolic blood pressure percentile for age (r = 0.55, p less than 0.05). Residual aortic narrowing did not significantly correlate with aortic stiffness, resting blood pressure gradient, or exercise blood pressure gradient. Neither left ventricular mass index nor resting systolic blood pressure percentile significantly correlated with age of repair or years after repair. These results demonstrate persistent abnormalities in aortic stiffness and left ventricular mass and function after successful repair of coarctation of the aorta in childhood and adolescence.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595542 TI - Effects of external constraint on the fetal left ventricular function curve. AB - To determine if external ventricular constraint significantly limits fetal left ventricular (LV) stroke volume and can thus account for the plateau of the fetal ventricular function curve, we studied nine fetal lambs (142 to 144 days' gestation) after partial delivery by cesarean section (halothane anesthetic). LV stroke volume (electromagnetic flow probe), LV end-diastolic pressure, and external ventricular constraint (intrapericardial pressure [liquid-filled balloon]) were measured over a range of end-diastolic pressures under two conditions: with a closed chest and closed pericardium and with an open chest and open pericardium. Stroke volume recorded during open chest and open pericardium exceeded those recorded during closed chest and closed pericardium at any given end-diastolic pressure (p less than 0.01). Decreases in external ventricular constraint significantly increased LV transmural pressure (preload) and substantially increased fetal LV stroke volume. Thus the plateau of the fetal ventricular function curve was largely a result of external ventricular constraint limiting LV preload, not necessarily a result of myocyte immaturity. PMID- 1595543 TI - Morphologic aspects of cardiac valve dysfunction. PMID- 1595544 TI - Abrupt coronary artery occlusion during percutaneous transluminal coronary angioplasty. PMID- 1595545 TI - Intravascular ultrasound in coronary atherosclerosis: a new approach to clinical assessment. AB - Intravascular ultrasound evaluation of the coronary arteries by means of a selective coronary catheter attached to an ultrasound unit has afforded precise depiction of coronary lumen diameter and area at the level of the catheter tip. The arterial wall at this level can be evaluated for lipid, fibrous tissue, calcification, wall dissections, and intraluminal thrombi. The technique has the advantage over coronary angioscopy and angiography in that it does not require infusions or injections to allow visualization, and it has the ability to depict the inside of the arterial wall. The current disadvantages include the inability to visualize the vessel segments distal to the catheter tip. Three-dimensional reconstruction techniques allow depiction of the segment of the artery traversed by the catheter tip. The use of Doppler ultrasound imaging provides information on coronary flow velocities through coronary obstructions. Intravascular ultrasound images may provide information that complements the coronary arteriogram and may have an impact on patient care and clinical investigation strategies. PMID- 1595546 TI - Does asymmetric mitral valve disease predict an adverse outcome after percutaneous balloon mitral valvotomy? An echocardiographic study. PMID- 1595547 TI - Transesophageal echocardiography in the diagnosis of flail tricuspid valve. PMID- 1595548 TI - Transesophageal echocardiographic detection of aortic atheromatosis may provide clues to occult renal dysfunction in the elderly. PMID- 1595549 TI - Percutaneous directional atherectomy for discrete coronary lesions in cardiac transplant patients. PMID- 1595550 TI - Self-limited acute pericarditis as initial manifestation of primary cardiac tumor. PMID- 1595551 TI - Intravascular ultrasound imaging in a patient with unstable angina. PMID- 1595552 TI - Posteromedial papillary muscle rupture as a result of right coronary artery occlusion after blunt chest injury. PMID- 1595553 TI - Junctional rhythm and atrial contraction: a mechanism for systolic sound. PMID- 1595555 TI - Echocardiographic manifestations of esophageal carcinoma. PMID- 1595554 TI - False positive signal-averaged ECG produced by junctional rhythm with retrograde P waves. PMID- 1595556 TI - Congenital complete heart block in a neonate. PMID- 1595557 TI - Echocardiographic diagnosis of a mycotic aneurysm of the main pulmonary artery and patent ductus arteriosus. PMID- 1595558 TI - Ehlers-Danlos syndrome with aortic regurgitation, dilation of the sinuses of Valsalva, and abnormal dermal collagen fibrils. PMID- 1595559 TI - Hypoplastic left heart syndrome: progression of left ventricular dilation and dysfunction to left ventricular hypoplasia in utero. PMID- 1595560 TI - Hypoplastic left heart syndrome: report of a case of spontaneous survival to adulthood. PMID- 1595561 TI - Mixed venous oxygen saturation in AMI. PMID- 1595562 TI - Anginal perception in diabetes. PMID- 1595563 TI - Toxic oil syndrome. PMID- 1595564 TI - Chagas' disease in the United States. PMID- 1595565 TI - Lovastatin on restenosis. PMID- 1595567 TI - Coronary-selective properties of nisoldipine. PMID- 1595566 TI - Amiodarone-cyclosporine interaction in cardiac transplantation. PMID- 1595568 TI - Carnitine and its acyl esters as secondary antioxidants? PMID- 1595570 TI - CPR at a college musical rehearsal. PMID- 1595569 TI - Toxoplasma myocarditis in AIDS. PMID- 1595571 TI - Auscultated growl of myocardial rupture. PMID- 1595572 TI - Does Chagas' disease exist as an undiagnosed form of cardiomyopathy in the United States? PMID- 1595573 TI - Recombinant interleukin-2 and recombinant interferon alpha immunotherapy cardiovascular toxicity. PMID- 1595575 TI - Bioelectrical-impedance analysis as a measure of body composition in a West Indian population. AB - Percent body fat (%BF) was estimated in 50 males and 50 females aged 8-21 y by using hydrodensitometry (%BFd) and a bioelectrical-impedance analyzer (%BF-BIA). The sample population was racially heterogeneous, though predominantly of African origin. Percent body fat was computed from density by using an equation derived specifically for blacks. The BIA predicted %BF with r2 = 0.77 (SEE = 3.7%BF), underestimating by a mean of 1.7%BF. Residuals (%BFd - %BF-BIA) were normally distributed but were significantly correlated with age (P less than 0.01), although this effect was small. The theoretical bases for impedance analysis and for hydrodensitometry would appear for different reasons to impair applicability of these techniques to the present population and age group. However, for our population sample the BIA estimated %BF as precisely as other simple techniques applied to other populations. PMID- 1595574 TI - Absolute fat mass, percent body fat, and body-fat distribution: which is the real determinant of blood pressure and serum glucose? AB - Associations of body mass index (BMI), absolute fat mass, percent body fat, and regional fat distribution with concentrations of fasting blood glucose and blood pressure were examined cross-sectionally in 1551 men and women aged 15-79 y from two study centers. Measurements included height, weight, multiple skinfold thicknesses, body density by underwater weighing, and waist and hip girths. Three principal findings emerged: 1) Absolute overall body mass and fat mass were stronger predictors of blood pressure and blood glucose than were relative fat mass, after age, height, and current cigarette-smoking status were adjusted for; 2) when diastolic blood pressure and serum glucose were used as the external validity criteria, densitometry was not a "gold standard" for body composition associated with risk for increased blood pressure and serum glucose; and 3) BMI was as good a predictor of blood pressure and glucose as was any other measure of body fat in nearly all analyses. PMID- 1595576 TI - Predicting body composition from anthropometry and bioimpedance in marginally undernourished adolescents and young adults. AB - Body-composition prediction equations were developed using data from a sample of 201 female and male Guatemalan ladinos (ie, people of Amerindian-European descent) aged 11-25 y. Fat-free mass (FFM) values were estimated from body density by using the two-component model and age- and sex-specific values for the density of FFM. The root-mean-square error (RMSE) of the best model predicting FFM from a set of simple anthropometric variables was 1.59 kg for females and 1.90 kg for males. The addition of more extensive anthropometry to the set of candidate predictors reduced the RMSE to 1.42 kg for females and 1.88 kg for males. The subsequent addition of a bioelectrical impedance measure (Ht2/R) further reduced the RMSE to 1.32 kg for females and 1.82 kg for males. These results suggest that for a marginally undernourished population with relatively little body fat, simple anthropometrics are as useful as more sophisticated measures for the prediction of body composition. PMID- 1595577 TI - Short-term effects of dietary-fat ingestion on energy expenditure and nutrient balance. AB - Joule for joule, dietary fat may promote obesity more than protein or carbohydrate. In this study we determined whether the addition of 50 g dietary fat to a standard breakfast would increase energy expenditure or fat oxidation during the immediate 6-h postprandial period or over the ensuing 18 h. We also determined whether subjects with a high level of aerobic physical fitness would show a greater increase in fat oxidation after the ingestion of the extra fat than would less fit subjects. Adding fat did not increase fat oxidation or energy expenditure either during the immediate 6-h postprandial period or over the following 18 h. This was true regardless of the subject's fitness level. Acutely, dietary fat ingested in excess of its usual rate of oxidation appears to be stored in the body. Being physically fit does not appear to provide an advantage in avoiding short-term storage of excess dietary fat. PMID- 1595578 TI - Twenty-four-hour energy expenditure in pregnant and nonpregnant Gambian women, measured in a whole-body indirect calorimeter. AB - Twenty-four-hour energy expenditure (EE), daily and sleeping EE, and the energy cost of a standardized treadmill exercise were assessed in a respiration chamber in 41 young pregnant Gambian women at 12 (n = 11), 24 (n = 15), and 36 (n = 15) wk of gestation and compared with 13 nonpregnant nonlactating (NPNL) control women. The rate of 24-h EE was significantly higher (P less than 0.001) at 36 wk gestation (8443 +/- 243 kJ/d) than in the NPNL group (6971 +/- 172 kJ/d) or at 12 and 24 wk (7088 +/- 222 and 7188 +/- 192 kJ/d, respectively). Per unit body weight, no more differences in 24-h EE, daily and sleeping EE, or energy cost of walking were observed between pregnant and NPNL women. There was no statistical difference in the 24-h respiratory quotient among the groups. We conclude that the state of pregnancy in Gambian women induces a progressive rise in 24-h EE, which becomes significant in the third trimester and is proportional to body weight. PMID- 1595579 TI - Change in waist-hip ratio with weight loss and its association with change in cardiovascular risk factors. AB - We investigated whether weight loss decreases the waist-hip ratio (WHR) in overweight men and women, and whether changes in WHR relates to change in cardiovascular risk factors, independent of change in weight. Weight loss correlated significantly with decreases in the circumference of the waist and hips, and decreases in WHR in men and women. At comparable levels of weight loss, men had greater decreases in the waist, and smaller decreases in the hips than women, resulting in greater decreases in WHR. Cardiovascular risk factors improved significantly with weight loss. However, after controlling for weight loss, there was no evidence that change in WHR or change in circumference measures were related to change in risk factors. These data suggest that WHR is modifiable by weight loss, especially in men, but that change in WHR may not be independently related to changes in cardiovascular risk factors. PMID- 1595580 TI - Food intake, hunger, and satiety after preloads in women with eating disorders. AB - Food intake, food selection, macronutrient intake, sensory-specific satiety, and ratings of hunger and satiety were measured after high- and low-energy salad preloads (2414 kJ, or 172 kJ) or no preload to determine whether patients with eating disorders compensate appropriately for different energy intakes. Subjects were female patients with a DSM-III-R diagnosis of anorexia nervosa with bulimic features or bulimia nervosa, or non patient, normal-weight, nondieters (n = 9/group). At a self-selected lunch 30 min after the preloads, all of the groups reduced intake after the high-energy preload, with the bulimics showing the best compensation. The anorexics chose low-energy foods and in some conditions ate a smaller proportion of fat than did the other groups. The bulimics ate more high energy foods than did the anorexics. The anorexics demonstrated sensory-specific satiety only after the high-energy salad and the bulimics only after the low energy salad. Overall, these data suggest that while many of their responses to food are abnormal, patients with eating disorders have some capacity to respond to physiological hunger and satiety cues. PMID- 1595581 TI - Infant-feeding practices and adiposity in 4-y-old Anglo- and Mexican-Americans. AB - A longer duration of breast-feeding and later introduction to solids may protect against excessive adiposity in infancy. This study investigated infant feeding practices and their relationship to two measures of adiposity--body mass index (BMI) and sum of skinfold thicknesses (SUMSF)--in 331 4-y-old Anglo- (43%) and Mexican-American (57%) children. No associations were detected between any of the infant feeding variables of duration of breast-feeding and introduction to solids and formula and measures of the child's adiposity. Mother's physical measures of BMI and SUMSF explained the largest portion of variance for both measures of childhood adiposity, BMI (9.5%), and SUMSF (8.3%). Genetic and environmental factors other than infant feeding practices appear to have a greater influence on a 4-y-olds' adiposity. PMID- 1595582 TI - Human milk intake and growth faltering of rural Mesoamerindian infants. AB - To determine whether growth faltering during early infancy was attributable to inadequate intake of human milk, the nutrient intakes and growth of 30 Otomi infants from Capulhuac, Mexico, were studied at 4 or 6 mo of age. Growth was monitored monthly from 1 through 6 mo of age. The 2H dose-to-the-mother method was used to measure human milk intake. Energy, protein, lactose, and fat concentrations in milk were analyzed by standard techniques. Mean (+/- SD) human milk intakes were 885 +/- 145 and 869 +/- 150 g/d at 4 and 6 mo, respectively. Protein and lactose concentrations in milk were normal but fat and consequently energy concentrations were abnormally low. Energy intakes averaged 81 +/- 14 kcal.kg-1.d-1 at 4 mo and 72 +/- 14 kcal.kg-1.d-1 at 6 mo. Growth faltering by 6 mo was evidenced by the significant decline in growth velocities and National Center for Health Statistics Z scores. Weight gain at 6 mo was 8.1 +/- 3.5 g/d and length gain was 1.0 +/- 0.34 cm/mo. Weight-for-age and length-for-age Z scores were -0.81 +/- 0.94 and -1.51 +/- 0.83, respectively. Growth velocities were not significantly correlated with nutrient intakes. Growth faltering among the Otomi infants despite energy intakes comparable to those of breast-fed infants in more protected environments may have resulted from an increase in the need for nutrients or from a growth-limiting nutrient, other than energy, in their diet. PMID- 1595583 TI - n-3 fatty acids in adipose tissue and coronary artery disease are inversely related. AB - The incidence of coronary heart disease is supposedly influenced by dietary fish oil intake. The purpose of this study was to investigate the possible beneficial effect of fish consumption on coronary atherosclerosis. Adipose-tissue biopsies and segments of coronary arteries were sampled from 40 consecutive autopsies. Degree of coronary artery disease was estimated quantitatively by morphometry, and the fatty acid composition of adipose tissue was analyzed with gas-liquid chromatography. The group with the highest degree (68-92% stenosis, n = 13) of coronary artery disease had lower concentrations of docosahexaenoic acid in adipose tissue than did the group with the lowest degree (23-53% stenosis, n = 13) of coronary artery disease (P less than 0.05). Multiple-regression analysis showed that the degree of coronary artery disease was dependent on docosahexaenoic acid in adipose tissue (P less than 0.01) and body weight (P less than 0.05). The study supports the hypothesis that fish consumption is associated with a reduced risk of coronary heart disease. PMID- 1595585 TI - Plasma amino acid concentrations in geriatric control and hip-fracture patients. AB - Changes in plasma amino acids, 24-h nitrogen balances, and resting metabolic expenditures (RMEs) were measured in 10 geriatric patients (aged 70-92 y) with hip fracture 1 d after surgical fixation during both a 24-h fasting state and while receiving total peripheral parenteral nutrition (TPPN) for 24 h at 1.5 g amino acids.kg-1.d-1 and 29-30 kcal.kg-1.d-1 and compared with 19 healthy volunteer subjects (aged 70-84 y). RME and 24-h urinary nitrogen losses were also elevated in the trauma patients during both fasting and TPPN. Positive nitrogen balances were evident in both groups during TPPN. Plasma total amino acid concentration was significantly lower in the trauma patients because of lower plasma concentrations of the nonessential amino acids. Phenylalanine and methionine concentrations were significantly higher and lysine lower in the trauma group. In addition, evaluation of the essential amino acid ratios after fasting and TPPN reveal that there are no limiting amino acids during TPPN. PMID- 1595584 TI - Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. AB - We determined serial changes in four major plasma carotenoid fractions (alpha carotene, beta-carotene, lutein/zeaxanthin, and lycopene) in 30 men consuming defined daily doses of carotenoids from foods (broccoli, carrots, or tomato juice) or from purified beta-carotene in capsules (12 or 30 mg) for 6 wk while fed a controlled diet. Compared with baseline, beta-carotene increased in the 30- and 12-mg-capsule and carrot groups whereas alpha-carotene increased in the carrot group and lutein increased in the broccoli group. Lower lutein concentrations in recipients of beta-carotene capsules suggested an interaction between these two carotenoids. Lycopene declined in all groups except the tomato juice group. Total carotenoid concentration changes only reflected the large increases in beta-carotene concentrations and not the smaller changes observed in other individual carotenoids. Overall, purified beta-carotene produced a greater plasma response than did similar quantities of carotenoids from foods sources. However, some foods increased plasma concentrations of certain carotenoids. PMID- 1595586 TI - Xerophthalmia and growth in preschool Indonesian children. AB - Approximately 4000 preschool children in West Java, Indonesia, were examined for xerophthalmia and weighed and measured at 3-mo intervals from March 1977 to December 1978. Children recovering from xerophthalmia over a 3-mo interval gained an average of 124 g (95% CI 42-206) more over 3 mo than normal children. Their height gain was similar to normal children's. Children who developed xerophthalmia during a 3-mo period gained 199 g (95% CI 114-313) less and grew 0.28 cm (95% CI 0.12, 0.44) less than their normal peers. Children with chronic xerophthalmia gained 120 g (95% CI 49-191) less and grew 0.21 cm (95% CI 0.05 0.37) less than normal children. These data suggest that linear and ponderal growth is adversely affected by chronic and incident xerophthalmia, but that catch-up ponderal growth is experienced by children recovering from xerophthalmia. PMID- 1595587 TI - Relative bioavailability of deuterium-labeled monoglutamyl tetrahydrofolates and folic acid in human subjects. AB - The bioavailability of orally administered monoglutamyl folic acid and various (6S)-tetrahydrofolates was examined in humans with stable-isotope methods. Folic acid (PteGlu), tetrahydrofolate (H4folate), 5-formyl-H4folate, 10-formyl H4folate, and 5-methyl-H4folate were prepared for oral administration in 3',5' 2H2 labeled (d2) form, and [glu-2H4]folic acid (d4-PteGlu) was prepared for intravenous injection. In each of five trials, fasting adult males (n = 7) on a folate saturation regimen (2 mg/d) were given a single oral dose of one of the d2 folates in apple juice, as well as an intravenous injection of d4-PteGlu as a control. Urine was collected for 48 h and the isotope labeling of urinary folates determined by mass spectrometry. Isotope excretion ratios of urinary folates were used as criteria of bioavailability (pooled SE = 0.10): PteGlu (1.53, least squares mean), 10-formyl-H4folate (1.02), 5-methyl-H4folate (0.99), 5-formyl H4folate (0.1.13), and H4folate (0.71). These results indicate that differences exist in the bioavailability of monoglutamyl folates under these experimental conditions. This variation, whether due to differences in absorption or postabsorptive events, must be considered in quantitative studies of folate utilization with this type of protocol. PMID- 1595588 TI - Effect of vitamin B-6 deficiency on fasting plasma homocysteine concentrations. AB - The catabolism of homocysteine through cystathionine synthesis requires pyridoxal 5'-phosphate, thus the effect of vitamin B-6 deficiency on plasma homocysteine concentrations was evaluated. Total fasting plasma homocysteine concentrations were measured in 11 elderly subjects aged 64.4 +/- 1.7 y (mean +/- SE) who consumed a vitamin B-6-deficient diet for less than or equal to 20 d. Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency. In a supporting study, fasting plasma homocysteine concentrations were measured in 3- and 23-mo-old rats fed vitamin B-6-deficient diets and were compared with those of vitamin B-6-replete, pair-fed controls. There was no difference in homocysteine concentrations between deficient and pair-fed animals after 6 wk of the dietary regimen for either age group; after 9 wk a modest elevation was observed in the 3-mo-old deficient rats whereas no difference was observed for the 23-mo-old rats. It is concluded that fasting plasma homocysteine concentrations are not initially elevated in vitamin B-6 deficiency and therefore fasting plasma homocysteine concentrations are not a good indicator of vitamin B 6 status. PMID- 1595589 TI - Daily magnesium supplements improve glucose handling in elderly subjects. AB - We demonstrated similar plasma concentrations and urinary losses but lower erythrocyte magnesium concentrations (2.18 +/- 0.04 vs 1.86 +/- 0.03 mmol/L, P less than 0.01) in twelve aged (77.8 +/- 2.1 y) vs 25 young (36.1 +/- 0.4 y), nonobese subjects. Subsequently, aged subjects were enrolled in a double-blind, randomized, crossover study in which placebo (for 4 wk) and chronic magnesium administration (CMA) (4.5 g/d for 4 wk) were provided. At the end of each treatment period an intravenous glucose tolerance test (0.33 g/kg body wt) and a euglycemic glucose clamp with simultaneous [D-3H]glucose infusion and indirect calorimetry were performed. CMA vs placebo significantly increased erythrocyte magnesium concentration and improved insulin response and action. Net increase in erythrocyte magnesium significantly and positively correlated with the decrease in erythrocyte membrane microviscosity and with the net increase in both insulin secretion and action. In aged patients, correction of a low erythrocyte magnesium concentration may allow an improvement of glucose handling. PMID- 1595590 TI - Effect of diet and lifestyle on bone mass in Asian young women. AB - The relationship between bone mineral content (BMC) divided by bone width (BW) and diet and lifestyle in early adulthood were investigated from the view point of preventing osteoporosis at a young age in Asian women. BMC/BW of 161 healthy Asian women aged 19-25 y were measured by single-photon absorptiometry. Current and past dietary habits and physical activity were also studied. BMC/BW varied from 0.21 to 0.48 g/cm2. Bone density correlated well with dietary habit from infancy to the present especially with calcium and past physical activity. These two factors showed additive effects on BMC/BW. In multiple-regression analysis, liking sports, body mass index, no milk intake in childhood, protein intake, frequency of dieting, and skipping meals were contributors to bone density and predictive of 23% of the variability in BMC/BW in the total group. The multiple regression coefficient was 0.518. Smoking, drinking, and duration of sunbathing might have no effect on BMC/BW in early adulthood. PMID- 1595591 TI - Direct evidence that primary acquired cell-mediated immunity is less resistant than is primary thymus-dependent humoral immunity to the depressive influence of wasting protein-energy malnutrition in weanling mice. AB - Wasting protein-energy malnutrition (PEM) was induced in male C57BL/6J mice fed a low-protein diet ad libitum from 23 to 37 d of age. In comparison with a complete diet, the low-protein formulation reduced delayed hypersensitivity to sheep red blood cells (SRBCs) assessed on day 14 of feeding by measuring increased footpad thickness (mean +/- SD: 4 +/- 4% vs 22 +/- 8%, P less than 0.01), after immunization on day 9, and after challenge with SRBCs on day 13. By contrast, the low-protein diet did not affect the anti-SRBC hemagglutinin titer (8.3 +/- 2.2 vs 9.1 +/- 1.1, P greater than 0.30) despite profound reduction in numbers of splenic plasma cells secreting IgM-class anti-SRBCs (7.3 +/- 3.1 vs 49.9 +/- 23.8 x 10(-3), P less than 0.001), after immunization on day 9 and assessment on day 14. Thus, direct experimental evidence, previously altogether lacking, is provided in support of the concept, central to nutritional immunology, that acquired cell-mediated immunity is less resistant than is systemic humoral immunity to the depressive influence of pre-adolescent, wasting PEM. PMID- 1595592 TI - Day-to-day variation in iron-status indices. PMID- 1595593 TI - Metastatic ovarian tumors: still a challenge. PMID- 1595594 TI - Medical appropriateness of laboratory tests. PMID- 1595595 TI - Metastatic ovarian carcinoma of large intestinal origin simulating primary ovarian carcinoma. A clinicopathologic study of 25 cases. AB - The distinction of metastatic ovarian carcinoma from a primary malignant ovarian neoplasm is crucial to its subsequent management. The most common metastatic carcinoma that mimics primary ovarian carcinoma is that of large bowel origin. The clinical and pathologic features of 25 cases of intestinal adenocarcinoma metastatic to the ovaries were analyzed. The patients ranged in age from 47 to 80 years (average age, 60 years). Most patients had abdominal pain and a pelvic mass. In 56%, the ovarian tumors and the large bowel carcinomas were discovered synchronously; 44% were metachronous. Seventy-five percent of the tumors were unilateral. Gross examination revealed that all the ovarian tumors were solid and cystic with smooth outer surfaces. Most of the tumors showed hemorrhage and necrosis. Histologic examination showed that 13 cases had a predominantly endometrioid-like pattern, four cases were predominantly mucinous, and the rest demonstrated a mixed pattern. The presence of a garland pattern with cribriform areas and "dirty" necrosis were the most distinctive features that were helpful in correctly differentiating these tumors from primary endometrioid ovarian carcinoma, with which they are often confused. Immunohistochemical stains for carcinoembryonic antigen showed strong intracytoplasmic positive staining in all the cases of intestinal adenocarcinoma metastatic to the ovaries, in contrast to primary ovarian endometrioid carcinoma, which stain negatively for carcinoembryonic antigen or show only intraluminal or apical positivity. As expected, intestinal adenocarcinoma metastatic to the ovaries had a very poor prognosis. Seventy percent of the patients died within a period of 1 to 19 months (average, 8.2 months). Its distinction from primary ovarian carcinoma is crucial because the management and prognosis of metastatic ovarian carcinoma of large intestine origin is different. PMID- 1595596 TI - Correlation of tumor cytosol cathepsin D with differentiation and invasiveness of endometrial adenocarcinoma. AB - The lysosomal acidic protease cathepsin D, a recognized independent predictor of prognosis in human breast cancer, has not been studied widely in patients with endometrial adenocarcinoma. Cathepsin D levels (52-kD precursor plus 48-kD intermediate and 34/14-kD mature form) were measured in tumor cytosols from 26 hysterectomy specimens by immunoradiometric assay. Significant correlation between cathepsin D levels and tumor differentiation was noted with linear increase in cathepsin D from 8 pmol/mg (standard error of the mean [SEM], 1.73 pmol/mg) for Grade I tumors to 28 pmol/mg (SEM, 3.91 pmol/mg) for Grade III tumors. A group of four papillary serous carcinomas showed relatively high cathepsin D levels reaching 39 pmol/mg. A significant stepwise increase in cathepsin D levels was associated with increased depth of myometrial invasion. Noninvasive tumors averaged 7 pmol/mg (SEM, 4.0 pmol/mg); intramural tumors averaged 15 pmol/mg (SEM, 2.45 pmol/mg); and transmural invasive tumors averaged 30 pmol/mg (SEM, 3.72 pmol/mg). There was no significant correlation of cathepsin D levels with age, estrogen/progesterone receptor hormone status, clinical stage, and lymph node metastasis. Cathepsin D levels correlate significantly with tumor differentiation and myometrial invasiveness and may show promise as a clinically useful adjunct to prognosis assessment and the planning of therapy for patients with endometrial adenocarcinoma. PMID- 1595597 TI - Lobular capillary hemangioma. An immunohistochemical study including steroid hormone receptor status. AB - Twenty-one lobular capillary hemangiomas (LCH), including lesions from six pregnant patients, were examined by immunohistochemical analysis. Antibodies to estrogen and progesterone receptor proteins were used to determine whether these steroid hormones play a direct role in LCH development and growth. All 21 LCHs were negative for both receptor proteins. Contrary to the association of LCH with pregnancy and oral contraceptive use, the absence of these steroid receptors strongly suggests that estrogen or progesterone are not directly involved in the formation of these lesions. All 21 LCHs were stained with Ulex europaeus lectin and with a panel of antibodies directed against cytokeratin, vimentin, Factor VIII, collagen Type IV, and muscle-specific actin. Endothelial cells in LCH, both in cellular proliferations with poorly formed lumens and in well-formed capillaries, were labeled by Factor VIII, Ulex europaeus lectin, and vimentin. A population of concentrically arranged, perivascular spindle-shaped cells was highlighted by positive staining for muscle-specific actin, collagen Type IV, and vimentin. The spindled cells were associated with both well-developed and immature vessels in all lesions. The appearance, immunophenotype, and location of these cells is consistent with a pericytic origin. Although the intimate association of both endothelial cells and pericytes suggests a reactive, as opposed to neoplastic, origin, other benign vascular tumors traditionally considered neoplastic have a similar bicellular composition. Accordingly, the findings neither support nor refute a neoplastic origin for LCH. PMID- 1595598 TI - Immunohistochemical distinction between amyloidosis and fibrillar glomerulopathy. AB - Six patients with glomerulonephritis and glomerular proteinaceous deposits constituted by fibrillar ultrastructures similar to those of amyloid but lacking the Congo red tinctorial affinity characterizing amyloid were studied. Clinically, these patients had proteinuria and hematuria; in addition, three patients had hypertension and one renal failure. Protein deposits in their kidney biopsy sections were evaluated by immunofluorescence, immunoperoxidase, and immunoelectron microscopic (protein A-gold) techniques, using antibodies against IgG, IgA, IgM, C3, C1q, fibrinogen, immunoglobulin kappa and lambda light chains, and against amyloid fibril proteins of different types, including AA, A lambda, A kappa, and AF. By immunofluorescence and immunoperoxidase, in all cases the deposits stained intensely with antibodies against IgG, C3, and kappa and lambda light chains; one case also showed C1q immunoreactivity. By contrast, none stained with antibodies against various amyloid fibril proteins. Immunoelectron microscopic findings corroborated this data, indicating that the nonamyloid fibrillar deposits studied are antigenically distinct from known amyloid deposits and that they contain IgG-derived material. PMID- 1595599 TI - Papillary adenofibroma of the uterus. Report of a case involved by adenocarcinoma and review of the literature. AB - An unusual case of uterine papillary adenofibroma involved by an invasive well differentiated adenocarcinoma is reported. The diagnosis was established using a hysterectomy specimen from a 68-year-old woman who was initially examined for abdominal pain and vaginal bleeding. The tumor was a broad-based polypoid mass composed of papillary projections into clefts and cysts. These papillations were covered by a variety of epithelial types and focally involved by an infiltrating adenocarcinoma. The stroma was fibrous and collagenized with variable numbers of benign fibroblasts. The papillary adenofibroma is considered to be a benign mixed tumor of Mullerian origin. Fifteen other cases of uterine adenofibroma have been reported in the literature and only one of these was focally involved by an adenocarcinoma. The clinical and histologic features of this rare disease are reviewed. PMID- 1595600 TI - Recurrent adult myofibromatosis. A case report. AB - Myofibromatosis generally is regarded as a fibrous proliferative disease of neonates and children that, even when multicentric, has an excellent prognosis and a propensity for spontaneous involution. Reported is a case of solitary, locally recurrent myofibromatosis in the ear canal of an adult patient. It was initially thought to be a leiomyoma. The diagnosis of myofibromatosis was made on the basis of its histologic appearance and corroborated by immunohistochemical stains. Clinicians and pathologists should be aware that myofibromatosis may occur in adults in unusual locations, with a potential for local recurrence. Furthermore, its histologic appearance may mimic that of other mesenchymal neoplasms. PMID- 1595601 TI - Pulmonary meningioma. Report of a case with electron microscopic and immunohistochemical findings. AB - A pulmonary meningioma was removed from a 55-year-old woman. She had no evidence of a cranial meningioma after a 3-year follow-up period. Results of immunohistochemical and electron microscopic studies of the tumor were similar to those for cranial meningiomas. The literature on this subject was reviewed and a possible origin for these tumors in the lung is discussed. PMID- 1595602 TI - A study of clinicians' responses to abnormal laboratory data as a function of diagnostic related group and test classification by College of American Pathologists criteria. AB - This study reports the frequency of new clinical orders, diagnoses, or testing after initial abnormal results of selected serum chemistry tests in 122 hospitalized patients at a Veterans' Administration Hospital. This study also reports the frequency of new orders, diagnoses, or testing after initial abnormal test results in relation to the test's classification as basic, common, less common, or unlisted in the workup and management of patients belonging to 24 common diagnostic related groups as classified by the College of American Pathologists. By chart review, initial abnormalities of serum potassium, creatinine, or blood urea nitrogen were most frequently followed by changes in treatment. For tests categorized as basic, abnormal creatinine and potassium were always followed by changes in treatment. Results were similar for tests categorized as common. Few abnormalities were found in tests categorized as less common. PMID- 1595603 TI - Hypomagnesemia in acute and chronic care patient populations. AB - The frequency and prevalence of hypomagnesemia (less than 0.72 mmol/L) in two divisions of a consolidated medical center with two distinct patient populations, acute and chronic, was studied. In the acute care patient population, the frequency and prevalence of hypomagnesemia was 41.4% (222 of 536 determinations) and 26.1% (92 of 353 patients) compared to a frequency of 12.5% (50 of 399 determinations) and prevalence of 3.5% (9 of 258 patients) in the chronic care population. Although the two divisions have similar numbers of hospital discharges, the acute care facility handles acute medical and all surgical cases, whereas the chronic care facility handles primarily psychiatric cases. In the acute care facility, the most common diagnoses associated with hypomagnesemia were coronary artery disease, malignancy, coronary artery bypass surgery, chronic obstructive pulmonary disease and alcoholism, whereas in the chronic care facility, alcoholism, liver disease, and carcinoma were the most frequent diagnoses associated with hypomagnesemia. The frequency and prevalence of hypomagnesemia in a patient population depends on the type of patient population studied and is significantly greater in the acute care compared to the chronic care patient population. PMID- 1595604 TI - Use of a more physiologic oral glucose solution during testing for gestational diabetes mellitus. AB - A lower osmolar oral glucose solution (50 g glucose in 450 mL fluid, 0.62 mol/L) was administered in addition to the standard hyperosmolar oral glucose solution (100 g glucose in 300 mL fluid, 1.85 mol/L) for oral glucose tolerance testing 1 week apart to 102 pregnant women. The standard oral glucose solution creates delayed gastric emptying and is associated with frequent nausea and vomiting. Results using the modified, lower osmolar glucose solution, when compared to the standard hyperosmolar glucose solution showed (1) statistically equivalent glucose excursion values 30 minutes after ingestion, (2) statistically significant decreased plasma glucose values greater than or equal to 60 minutes, (3) no statistically significant difference in insulin excursion values 30 minutes after ingestion, (4) equal area under the curve for glucose at 30 minutes using either solution, and (5) a markedly decreased incidence of nausea and vomiting. These data suggest that the modified, lower osmolar glucose solution empties rapidly from the stomach and allows the glucose to be absorbed and enter the peripheral circulation in an expeditious manner. PMID- 1595605 TI - The laboratory assessment of fetal lung maturity. AB - The assessment of fetal lung maturity by laboratory methods is reviewed, and the utility of the various approaches in the prediction of respiratory distress syndrome is discussed. Because of the relatively low prevalence of respiratory distress syndrome, methods with exceptionally high diagnostic sensitivity and specificity are required; such methods are rarely available for any diagnostic evaluation, and the methods with the greatest clinical acceptance in assessing fetal lung maturity have been those which require the most personnel time and skill. The consequences of laboratory testing in the environment of low prevalence diseases is discussed. Because of the clinical implications of an erroneous determination of fetal lung maturity, particularly in the case of incorrectly assessing the fetal lungs to be mature, a strong emotional overlay exists for accepting only the "reference method" or "gold standard" in this determination. This review briefly discusses the utility of commonly used methods in the context of the physical and chemical concepts. By reviewing the underlying principles of the methods, the origins of some of the frequently observed problems in this field are revealed. The emphasis is on practical application and issues of use both to clinician and laboratory in approaching this controversial and difficult area of assessment. It is demonstrated that there are several reasonably straightforward approaches which will provide appropriate clinical information more quickly, easily, and inexpensively than the methods generally requested. PMID- 1595606 TI - A blood culture study comparing the new Bactec high-volume resin media with hypertonic media. AB - A blood culture study comparing the performance of the new high-volume Bactec resin media to hypertonic medium was conducted in adult patients seen in the emergency department. Twenty milliliters of blood was divided equally among three media: hypertonic (NR8A), aerobic high-volume resin (HV26), and anaerobic high volume resin (HV27). During a 5.5-month period, 2,724 blood cultures were collected; there were 417 (15.3%) positive cultures, of which 233 (8.6%) yielded pathogens and 184 (6.8%) contaminants. For the 257 isolates recovered from 233 cultures yielding pathogens, the isolation rates were: NR8A-194 (75.5%), HV26-204 (79.4%), and HV27-189 (73.5%). We conclude that in this emergency department patient population, the rate and speed of recovery of pathogenic microorganisms is comparable in high-volume resin media and the hypertonic medium but that the high-volume resin media still has a definite advantage over standard nonradiometric media in adults because high-volume blood cultures (20 mL) can be performed using a two-bottle collection set rather than a three-bottle set. PMID- 1595607 TI - Evaluation of a rapid peptide-based anti-human immunodeficiency virus-1 antibody immunoassay. AB - A qualitative, visually interpreted, rapid, and synthetic peptide-based anti human immunodeficiency virus-1 (HIV) antibody immunoassay has been developed that may be of value in situations in which rapid determination of HIV-1 status is important. Because questions have been raised about the accuracy of rapid anti HIV-1 assays, the sensitivity, specificity, interobserver and intraobserver variability of the Genie HIV-1 assay (Genetics Systems, Seattle, WA) were determined. Sera from 56 patients with HIV-1 infections documented by enzyme immunoassay and western blot tested positive by this assay. Enzyme immunoassay- and western blot-negative sera from 30 visceral organ transplant donors were negative using the Genie assay. Specificity was examined further by testing sera from 29 patients hospitalized with a variety of medical disorders, including acute bacterial pneumonia, acute myocardial infarction, monoclonal gammopathy, and high titer antinuclear or antimitochondrial antibodies. Two of these patients were reactive with the enzyme immunoassay, both of which tested negative by western blot. All 29 tested negative using the Genie assay. In addition, sera from five patients with repeatedly reactive enzyme immunoassays and negative western blots tested negative by the Genie system. There was 100% agreement in interobserver and intraobserver studies. With the western blot as the reference method, the Genie assay exhibited 100% sensitivity and specificity and there was no observer variability. PMID- 1595608 TI - The "CD43 only" phenotype. An aberrant, nonspecific immunophenotype requiring comprehensive analysis for lineage resolution. AB - Paraffin section immunohistology of leukocytic proliferations is a routine method of immunophenotyping in many clinical laboratories. Furthermore, a relatively standard antibody screening panel that includes L26 (CD20), Leu22 (CD43), and UCHL1 (CD45RO) appears to be widely used. Although paraffin section immunophenotyping in general, and this panel in particular, have been shown to be very reliable in defining B-cell lineage, characterization of T-cell lineage is less definitive. This is related primarily to the relatively poor specificity of the commercially available T-cell-associated reagents. CD43 (Leu22) in particular has a broad immunoreactivity profile that has not been stressed adequately in some reports. Seventeen cases with a "CD43 only" phenotype were identified during the last several years while using the relatively standard screening panel mentioned above. These cases were quite heterogeneous with respect to cellular differentiation and most were not T-cell proliferations. Specifically, eight cases were extramedullary leukemic infiltrates (five myeloid, two monocytic, one mixed lineage), four cases were T-cell lymphomas, three cases were B-cell lymphomas and two cases were plasmacytomas. Although CD43 has demonstrable utility in a leukocyte screening panel, this report stresses the aberrancy and lack of specificity of the "CD43 only" phenotype. Caution is recommended in assigning a specific lineage to such cellular proliferations without additional immunologic or genotypic analysis. Recommendations for comprehensive diagnostic evaluation of these proliferations are provided. PMID- 1595609 TI - Accurate counting of low numbers of leukocytes. Use of flow cytometry and a manual low-count chamber. AB - The leukocyte depletion that current filters make possible in erythrocyte and platelet preparations can result in leukocyte concentrations too low to be counted accurately by automated and standard manual methods. A recently described method for counting low numbers (1 to 10 x 10(6) per L) of leukocytes by flow cytometry and the use of a manual low-count chamber on 25 venous samples serially diluted to 1:1,000 were evaluated. The results show that both methods for counting leukocytes can reliably determine counts of 1 to 10 x 10(6) leukocytes/liter (a three-order of magnitude reduction from venous blood) in terms of order of magnitude but lack accuracy for specific measurement. The flow cytometric method is more expensive, less readily available, and suffers from greater sample variability. Use of a low-count chamber is a superior technique to evaluate and maintain quality control of methods for leukocyte depletion, resulting in a final leukocyte concentration of 1 to 10 cells per microliter. PMID- 1595610 TI - Rapid immunocytochemical analysis of acute leukemias. AB - Immunophenotypic analysis of acute leukemias is time consuming and often requires flow cytometric analysis. A 1-hour alkaline phosphatase-labeled streptavidin biotin immunocytochemical procedure was evaluated as an alternative. Seventeen cases of acute leukemia, including 10 acute lymphocytic (ALL) and 7 acute nonlymphocytic, were phenotyped by the rapid immunocytochemical procedure and the results were compared with standard analyses. In all 17 cases, the diagnoses made using standard cytochemical and immunologic methods were the same as obtained in blinded reviews by rapid immunocytochemical analysis. Nine cases of precursor B cell ALL were positive for CD19 and/or CD22. Five CD19 + cases of ALL reacted with anti-myeloperoxidase, with one case also positive for CD15. CD15 positivity was confirmed on repeated study as well as with plastic section immunoperoxidase staining. Nine cases of ALL were positive for CD10 and eight were positive for terminal deoxynucleotidyl transferase. One case of ALL marked as T-cell ALL with CD1, CD2, CD3, and CD7. All cases of acute nonlymphocytic leukemia were positive for CD15, CD13, and/or CD33; anti-myeloperoxidase was positive in all but one case of monocytic leukemia. All cases of acute nonlymphocytic leukemia were negative for CD10 and one was positive for terminal deoxynucleotidyl transferase. Acute leukemias apparently may be phenotyped easily and accurately in 1 hour with this immunocytochemical technique, and slides may be stored permanently for review. There was in these 17 cases high correlation of the diagnoses with standard flow cytometric and cytochemical results. This rapid method allows a coordinated evaluation of morphologic features and immunophenotype; the latter features facilitated confirmation of unexpected reactivity of myeloid markers CD15 and MPO-7 in some cases of ALL. PMID- 1595611 TI - A comparative analysis of cytoplasmic mu (C mu) expression in acute lymphoblastic leukemia by molecular and immunologic techniques. Identification of leukemia cases expressing C mu mRNA transcripts in the absence of detectable C mu proteins. AB - Among acute lymphoblastic leukemias derived from the B-cell lineage, the subset of cases expressing cytoplasmic mu heavy chain proteins (C mu) in the absence of surface immunoglobulin has been designated pre-B-cell acute lymphoblastic leukemia. This group, traditionally identified using immunologic smear techniques, has been associated with a poor prognosis in some series. In a comparative study, 25 cases of B-lineage acute lymphoblastic leukemia were analyzed for C mu expression using molecular and immunologic techniques. RNA derived from cryopreserved blast cells was hybridized in both Northern and slot blot analyses using a probe (pBZ311) containing four exons of the human immunoglobulin heavy chain mu constant region gene. Expression of C mu proteins was assessed simultaneously by slide immunofluorescence and flow cytometric techniques in all samples. These studies were correlated with immunoglobulin heavy and light chain gene rearrangements, cell-surface immunophenotype, cytogenetics, and other clinicopathologic features. C mu mRNA transcripts were detected in 14 of 25 cases, whereas C mu proteins were detected in only 9 of these cases using flow cytometric techniques. Only four of these nine cases were positive by slide immunofluorescence techniques. These studies imply that molecular and flow cytometric techniques may be a more sensitive means to assess C mu expression. The identification of five cases that expressed C mu mRNA transcripts in the absence of detectable C mu proteins also suggests that molecular techniques may be valuable in identifying a unique subgroup of pre-B cell acute lymphoblastic leukemia cases that contain C mu mRNA transcripts, but lack C mu proteins. PMID- 1595612 TI - Desmin-negative intranodal leiomyoma. PMID- 1595613 TI - Electron microscopic evidence of Treponema pallidum and Helicobacter pylori in gastric tissue. PMID- 1595614 TI - Hot embers and ashes as sources of burns in children. PMID- 1595616 TI - Water intoxication. PMID- 1595615 TI - Water intoxication. PMID- 1595617 TI - Nail-bed lines in Kawasaki disease. PMID- 1595619 TI - Health care for poor children in the United States: a full-time vs part-time solution. PMID- 1595618 TI - Dietary calcium and bone health. PMID- 1595620 TI - Kiss: a developmental milestone or a culture-determined skill? PMID- 1595621 TI - Violence and children in the United States. PMID- 1595623 TI - Gangs, drugs, and homicide in Los Angeles. AB - OBJECTIVE: To assess the theory that youth homicides in Los Angeles, Calif, are largely attributable to gang involvement in the trafficking or use of drugs. DESIGN, SETTING, AND PARTICIPANTS: First, we analyzed all homicides in a police database that occurred in Los Angeles between January 1, 1986, and August 31, 1988, to examine the association between gang activity and narcotic use and trafficking. Second, we used detailed data from police files to examine the same associations for a subset of homicides in south central Los Angeles. Third, we investigated the association between gang homicide victimization and victim cocaine use for all 1987 Los Angeles homicides. Finally, we compared narcotics arrest histories for gang homicide victims with histories for other homicide victims. RESULTS: Gang-motivated homicides were less likely than other homicides to involve narcotics, and narcotics-motivated homicides were less likely to involve a gang member. Victims of gang-motivated homicides in 1987 were less likely than other homicide victims to have detectable levels of blood cocaine. Finally, young victims of gang-involved homicide were no more likely to have a history of narcotics arrests than other victims. CONCLUSIONS: Our investigation does not support the theory that a substantial proportion of homicides are attributable to gang involvement in narcotics trafficking. PMID- 1595622 TI - Gun-related violence in and around inner-city schools. AB - OBJECTIVE: To assess the degree to which inner-city high school students are victimized by threat of or actual firearm attack. DESIGN: Cross-sectional survey. SETTING: Ten inner-city high schools in five cities in four states. PARTICIPANTS: A total of 1653 male and female inner-city high school students responding anonymously. SELECTION PROCEDURES: Volunteer, convenience sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Twenty-three percent of respondents were classified as victims. Major variables predicting victimization levels were gender, number of siblings, exposure to violence outside of school, and personal violence-related attributes. Only one in 10 victimizations appeared to be random (ie, not predicted by these variables). CONCLUSIONS: Violence in school is brought into, rather than generated by, the school. Victimized students have characteristics that put them at higher risk of victimization than other students. Given the large number of victimizations and the large number of respondents with risk characteristics, intervention at the individual level seems ineffective. Instead, alteration of community social structure and culture appears to be the appropriate, although difficult, avenue of change for gun related victimization levels. PMID- 1595624 TI - The diagnosis of child sexual abuse. AB - OBJECTIVE: To examine how the history, psychological evaluation, medical examination, and child's response to the examination contributed to a diagnosis of child sexual abuse by an interdisciplinary team. DESIGN: Patient series. SETTING: Subspecialty clinic for evaluating prepubertal children alleged to have been sexually abused. PARTICIPANTS: One hundred thirty-two children alleged to have been sexually abused and their parents or guardian, evaluated consecutively in a subspecialty clinic between September 1989 and June 1990. MEASUREMENTS/MAIN RESULTS: A social worker interviewed the parents, a psychologist interviewed the child, and a pediatrician obtained a medical history and examined the child. Parents completed a Child Behavior Check list and the child's response to the physical examination was noted. Both a disclosure by the child and abnormal physical findings were significantly and independently associated with the team's diagnosis of sexual abuse, whereas the presence of sexualized behavior, somatic problems, and the child's response to the examination did not make an additional contribution to the diagnosis. CONCLUSIONS: The findings support the need for a skilled psychological interview and a medical examination of a child alleged to have been sexually abused to make the diagnosis of sexual abuse. An interdisciplinary team appears to be a valuable approach for evaluating these children and their families. PMID- 1595625 TI - Zinc-induced copper deficiency in an infant. AB - OBJECTIVE: To describe the case of a 13-month-old girl who developed copper deficiency as a result of excessive zinc gluconate ingestion. SETTING: Tertiary care hospital in Syracuse, NY. INTERVENTIONS: Cessation of zinc ingestion followed by intravenous and oral copper chloride therapy. MEASUREMENTS/MAIN RESULTS: Ingestion of zinc gluconate, 120 mg/d for 6 months, and thereafter 180 mg/d for 1 month, preceded the clinical presentation of listlessness, anemia, neutropenia, poor weight gain, abnormal sparse hair, and scorbuticlike bone changes. Findings on a bone marrow examination included ring sideroblasts and suggested copper deficiency. Plasma zinc level was 36.7 mumol/L, serum ceruloplasmin level was 20 mg/L, and serum copper level was undetectable. Clinical and laboratory abnormalities resolved shortly after initiation of copper therapy. CONCLUSIONS: This case demonstrates the reciprocal relationship of copper and zinc metabolism and exemplifies the important interrelationships of dietary trace minerals. PMID- 1595626 TI - Measured vs calculated plasma osmolality in infants with very low birth weights. AB - OBJECTIVE: To determine the relationship between measured serum osmolality (MsOsm) and calculated osmolality and to examine factors that may affect the osmolal gap. RESEARCH DESIGN: Longitudinal cohort study. SETTING: Regional tertiary neonatal intensive care nursery in a university-affiliated hospital. PATIENTS: Sixty low-birth-weight infants (birth weight, 540 to 1500 g), studied daily during the first week of life. SELECTION PROCEDURE: Consecutive sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The MsOsm was significantly higher than the calculated osmolality for the first 6 days of life. The MsOsm was significantly higher during the first 6 days of life in infants with birth weights less than 1000 g than in those with birth weights greater than 1000 g, but the calculated osmolality was similar in both groups. Intraventricular hemorrhage, preservative additives in drugs, and packed red blood cell transfusions did not contribute significantly to osmolal gap or MsOsm. In 19 patients, peak MsOsm was greater than or equal to 320 mmol/kg (mean, 336 +/- 13 mmol/kg; calculated osmolality, 298 +/- 20 mmol/kg; osmolal gap, 38 +/- 19 mmol/kg). Six of these 19 patients died (all with birth weights less than 1000 g). CONCLUSIONS: A significant proportion of patients with very low birth weights (mostly less than 1000 g) have large osmolal gaps and/or an MsOsm greater than 300 mmol/kg during the first week of life. The relationship between increased MsOsm in infants with very low birth weights and effective osmolality requires further study. Therapeutic intervention based solely on elevated MsOsm is ill advised. PMID- 1595627 TI - Acid peptic disease in children with type I diabetes mellitus. A complicating relationship. AB - OBJECTIVE: To determine the prevalence of acid peptic disease among pediatric patients with insulin-dependent diabetes mellitus and to study the effects of acid peptic disease on treatment of insulin-dependent diabetes mellitus. DESIGN: Inception cohort and matched case-control study, with a data set derived from patient and parent interviews and inpatient and outpatient chart reviews. SETTING: LeBonheur Children's Medical Center, a university-affiliated hospital in Memphis, Tenn. PARTICIPANTS: Thirty-one patients with insulin-dependent diabetes mellitus who presented with multiple episodes of symptoms of acid peptic disease were examined by endoscopy. Thirty-one control patients with insulin-dependent diabetes mellitus and transient or no gastrointestinal complaints were matched for age, gender, race, and duration of diabetes. MEASUREMENTS: Glycosylated hemoglobin levels, stature, frequency of hospital admissions, and parental history of acid peptic disease. RESULTS: Acid peptic disease occurred with a prevalence of 7% in our population of pediatric patients with insulin-dependent diabetes mellitus. Major endoscopic findings included gastritis confirmed by upper gastrointestinal biopsy (94%), bile staining of gastric mucosa (58%), and bile pooling (52%). Patients with acid peptic disease demonstrated shorter stature, greater frequency of hospital admissions, and greater prevalence of parental acid peptic disease by history than those of controls. In the 18 months following acid peptic disease therapy, hospital admissions for diabetes-related problems decreased by 50%. CONCLUSIONS: Acid peptic disease is an underrecognized complicating factor in the treatment of diabetes. Clinical suspicion is necessary to offset compromised diabetes control, compliance to treatment regimens, and/or growth expectations associated with this disease. PMID- 1595628 TI - Cerebral palsy and the 'bad baby' malpractice crisis. New York State shines light toward the end of the tunnel. PMID- 1595629 TI - The impact of health care financing on childhood immunization practices. AB - OBJECTIVE: To examine the impact of patient insurance status and third-party payment methods on physician immunization practices. DESIGN: Family practice physicians and pediatricians were surveyed to determine whether differences existed in office immunization practices for five childhood vaccines across insurance and payment classes. SETTING: Milwaukee, Wis. PARTICIPANTS: Of 202 Milwaukee area physicians who administer immunizations routinely, 161 (79.7%) returned the questionnaire. RESULTS: Physicians reported immunizing uninsured patients in their offices less often than patients with insurance. When insurance does not pay for immunizations, most physicians (81.6%) said that they left the decision of whether to pay for private immunizations or seek free immunizations from the city health department to the family. Physicians estimated that approximately half of their uninsured patients decline private immunizations. Some physicians (20%) who treat patients receiving Medicaid reported that they immunize patients with Title 19 coverage less often than patients with other types of insurance. No significant differences in frequency of immunization were reported for patients insured by capitated-payment health maintenance organizations, fee-for-service health maintenance organizations, or traditional insurance covering immunizations. CONCLUSIONS: Physicians reported that they do not immunize uninsured and underinsured children as frequently as insured children. Further research is recommended to evaluate the impact of Medicaid enrollment on access to immunization and to develop innovative financing arrangements to ensure that no children leave their physicians' offices without being immunized. PMID- 1595630 TI - The fasciitis-morphea complex in children. AB - OBJECTIVE: To describe the clinical presentation and treatment of the combined syndrome of fasciitis and morphea in children. SETTING: The rheumatic disease clinic of a university children's hospital. PATIENTS: Six children who were referred for signs or symptoms of fasciitis were observed. SELECTION PROCEDURES: All children who were referred for fasciitis were included in the study. INTERVENTIONS: Therapy included prednisone initially and subsequent long-term treatment with penicillamine and alternate-day doses of prednisone. MEASUREMENTS AND RESULTS: Symptoms of morphea appeared 1 year before to 4 years after the first signs of fasciitis were observed. The fasciitis was characterized by usually symmetrical, centrifugal swelling, pain, and contracture formation. The morphea and fasciitis did not appear in the same areas of the body. CONCLUSIONS: The fasciitis and morphea are clearly linked manifestations. The fasciitis, but not the morphea, appears to respond to treatment with steroids. Treatment with penicillamine may ameliorate the sclerosis of the morphea but does not stop new lesions from appearing. PMID- 1595631 TI - Cerebral blood flow velocity in normal, full-term newborns is not related to ductal closure. AB - OBJECTIVE: To correlate changes in blood flow velocity in the anterior and middle cerebral arteries with closure of the ductus arteriosus in normal, full-term newborns during the first 2 days following delivery. DESIGN: Survey. SETTING: Large community hospital. PARTICIPANTS: Twenty-three normal, full-term neonates. SELECTION PROCEDURES: Volunteer sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We measured blood flow velocity in the anterior and middle cerebral arteries, cardiac output, and patency of the ductus arteriosus using pulsed Doppler, M-mode, and real-time ultrasound. The initial examination was performed at (mean +/- SD) 7.6 +/- 2 hours and the second examination was performed at 30 +/- 3 hours. The systolic, diastolic, and mean blood flow velocity in the anterior and middle cerebral arteries increased significantly from day 1 to day 2. Cardiac output did not change significantly (252 +/- 49 vs 279 +/- 69 cm3/kg per minute). Thirteen newborns on day 1, but only two newborns on day 2, had echocardiographic evidence of a patent ductus arteriosus. Newborns whose ductus was already closed on day 1 had similar increases in blood flow velocity in the anterior and middle cerebral arteries from day 1 to day 2 compared with newborns whose ductus had closed from day 1 to day 2. CONCLUSION: The normal increase in blood flow velocity in the anterior and middle cerebral arteries in the first 2 days following delivery is not related to changes in cardiac output or ductal closure. PMID- 1595632 TI - Children's ice hockey injuries. AB - OBJECTIVE: To determine the rate, type, and severity of injuries to child hockey players as well as assessing coaches', parents', and players' attitudes and knowledge of hockey. DESIGN: A prospective observation of a population's injuries using injury-reporting forms and surveys. SETTING: A community-organized hockey program in Minnesota. PARTICIPANTS: One hundred fifty boys, aged 9 through 15 years, who played ice hockey during the 1990-1991 winter season. MEASUREMENTS AND MAIN RESULTS: Injuries were reported by multiple observers, including coaches, managers, and trained independent observers at the time an injury occurred; coaches, parents, and players were surveyed regarding hockey injuries, knowledge, and attitudes. One in three players experienced an injury during the season. The most common injuries were contusions. Six of 100 players experienced injuries severe enough to require cessation of physical activities for 8 to 25 days or longer. Weight differences of 53 kg and height differences of 55 cm were reported between Bantam-aged players (13 through 15 years), and body contact, including legal checks, accounted for 86% of injuries during games. Illegal checks and violations were associated with 66% of injuries during games, yet only four penalties (14%) were assessed. In addition, one in three games in which an injury resulted was described as hostile and 15% of the injuries were considered intentional. CONCLUSIONS: Eliminating violence and body checking for prepubertal boys while emphasizing rule enforcement and good sportsmanship are recommended. PMID- 1595633 TI - Electroencephalographic and behavioral-state studies in infants of cocaine addicted mothers. AB - OBJECTIVE: To evaluate cerebral cortical function with electroencephalography in infants of cocaine-addicted mothers. DESIGN: Patient series. SETTING: The Children's Hospital of Philadelphia (Pa). PARTICIPANTS: Thirty-five consecutive infants of cocaine-addicted mothers hospitalized for a comprehensive health assessment and 51 healthy, age-matched infants studied with electroencephalography and respiratory thermistor because they were siblings of sudden infant death victims (comparison group). INTERVENTIONS: None. MEASUREMENTS/MAIN RESULTS: Behavioral states during spontaneous daytime sleep were classified as active sleep or quiet sleep; quiet sleep was further characterized as immature, trace alternant sleep or mature, continuous, slow wave sleep. No episodes of ictal apnea or nonictal apnea were recorded in infants of cocaine-addicted mothers; nonictal apnea was observed in one control patient. No electrographic seizures were recorded. There were no significant differences between the proportions of infants exposed to cocaine in utero and that of controls who displayed excessive sharp electroencephalographic transients, background abnormalities, immaturity, and hypermaturity. Electroclinical sleep discordance was present in 5.7% of infants of cocaine-addicted mothers vs 0% of controls. Cocaine-exposed infants displayed mature, continuous, slow wave sleep below 45 weeks of conceptional age in a significantly higher percentage than those in the comparison group. CONCLUSIONS: Although frank electroencephalographic abnormalities were infrequent in infants whose mothers were addicted to cocaine, they differed significantly in their younger age of onset of continuous, slow wave sleep. Our findings provide continued reason for concern that infants of cocaine-addicted mothers may suffer subtle adverse neurologic, cognitive, or behavioral effects later in life. The longitudinal assessment of sleep disturbance and its relation to later development might permit tracking of the long-term effects of prenatal exposure to cocaine. PMID- 1595634 TI - The persistent parent. AB - Parental persistence in the diagnosis and treatment of a child's illness can be examined by asking whether it is congruent with the child's morbidity. The relationship between parental persistence and child morbidity always depends on a "first diagnosis" (ie, what is wrong with the child, if anything?). In many instances, a "second diagnosis" (ie, why is the child being brought to you at this time?) should not be overlooked. First and second diagnoses are identical if persistence and morbidity are congruent but are different if they are incongruent. Once incongruent persistence is suspected, the possibility of parental falsification of symptoms must be faced. In patients in whom a second diagnosis must be made, the second diagnosis may be as simple as maternal anxiety or as complex as Munchausen syndrome by proxy. A "persistence algorithm" is presented and illustrated by descriptions of four children referred to a pulmonologist with complaints suggestive of respiratory disease. The approach, as outlined in the algorithm, may have broad pediatric applications. PMID- 1595636 TI - Radiological case of the month. Pathologic phimosis. PMID- 1595635 TI - The psychologic fallout from Chernobyl. PMID- 1595637 TI - Radiological case of the month. Acute iron poisoning and gastrointestinal decontamination procedure. PMID- 1595638 TI - Pathological case of the month. Hereditary tyrosinemia type I. PMID- 1595640 TI - Gastroenterology today and tomorrow. PMID- 1595639 TI - Incorporating randomized clinical trials into clinical practice: maintenance treatment for Crohn's disease. PMID- 1595641 TI - Nonobstructive dysphagia in gastroesophageal reflux disease: a study with combined ambulatory pH and motility monitoring. AB - Nonobstructive dysphagia is a common symptom of gastroesophageal reflux disease, and may be present in up to 45% of patients. To elucidate the mechanism of dysphagia, stationary and ambulatory motility studies were performed in 10 controls and 27 patients with gastroesophageal reflux disease. Sixteen patients had nonobstructive dysphagia and 11 had no dysphagia. During stationary studies, there was essentially no difference in esophageal body motility among all the groups. Lower esophageal sphincter manometry was similar in patients with or without dysphagia. On ambulatory motility, about 40% of contractions in the body of the esophagus were simultaneous in the supine position in controls and both groups of patients. The rate of simultaneous contractions decreased in the upright position and at mealtimes in controls and in patients without dysphagia, but not in those with dysphagia. This resulted in a higher percentage (38%) of intraprandial simultaneous wave activity in patients with dysphagia than in those without dysphagia (23%) or in controls (13%) (p less than 0.05). Patients with reflux disease who suffer from nonobstructive dysphagia therefore have a motility disorder measurable on ambulatory motility studies which results in an increased percentage of nonperistaltic (simultaneous wave) activity during mealtimes. PMID- 1595642 TI - Manometry during food ingestion aids in the diagnosis of diffuse esophageal spasm. AB - It has been shown that food ingestion can provoke esophageal motor abnormalities in patients with otherwise normal manometry. Such motor abnormalities are usually nonspecific in character. We now report water swallow and food ingestion data on 12 patients with a history of dysphagia and/or chest pain who satisfied strict manometric diagnostic requirements for diffuse esophageal spasm. Three of these patients had normal water swallow manometry, yet, during food ingestion, showed manometric evidence of diffuse esophageal spasm. In the other nine patients, the occurrence of nonperistaltic contractions was greater, and there was a greater incidence of nonperistaltic contractions of 100 mm Hg or more after ingestion of food. We conclude that food ingestion increases the diagnostic yield of manometric testing for diffuse esophageal spasm and, not infrequently, magnifies an abnormality seen during standard water-swallow testing. PMID- 1595643 TI - Abnormal growth hormone responsiveness to stimuli in women with active celiac sprue. AB - Baseline somatomedin C (Sm-C) and responses of growth hormone (GH), prolactin (PRL), and thyrotropin (TSH) to TSH-releasing hormone (TRH) and to L-dopa were evaluated in 10 untreated and nine treated women with celiac sprue, and in 10 normal women. Mean basal Sm-C, GH, PRL, and TSH levels were similar in all groups of subjects. In all subjects, L-dopa decreased PRL levels, without affecting TSH, and TRH increased PRL and TSH levels. In both controls and treated patients, TRH did not influence GH secretion, whereas L-dopa significantly increased GH levels. In untreated patients, GH levels paradoxically increased after TRH (8/10) but were unaffected by L-dopa (7/10). Because L-dopa would stimulate hypothalamic GH releasing hormone (GHRH) secretion, four untreated patients, unresponsive to L dopa, received GHRH, and GH levels rose markedly. These data suggest that, in untreated celiac sprue patients, hypothalamic control of GH secretion is reversibly impaired. PMID- 1595644 TI - Glucose malabsorption associated with rapid intestinal transit. AB - Twenty-five patients with chronic diarrhea were studied with a combined glucose hydrogen breath test (GHBT) and nuclear transit scan to elucidate the role of abnormal transit in the pathogenesis of diarrhea. Eight of the 25 patients demonstrated both a rapid orocecal transit time by nuclear scan (less than 30 min) and a positive hydrogen breath test (greater than 20 ppm increase in H2 after a 50-g glucose challenge). Because these individuals had no anatomic abnormalities predisposing to small bowel bacterial overgrowth, it is probable that they demonstrated colonic bacterial metabolism of carbohydrate secondary to glucose malabsorption associated with rapid small bowel transit. The eight patients exhibited some form of autonomic dysfunction generally related to systemic disease. Thus, there may be a subset of patients with chronic diarrhea related to rapid intestinal transit. A combined GHBT-nuclear transit scan permits accurate identification of such individuals and improves the accuracy of hydrogen breath tests in the diagnosis of bacterial overgrowth. PMID- 1595645 TI - Stability of pH gradients in vivo across the stomach in Helicobacter pylori gastritis, dyspepsia, and health. AB - A layer of water-insoluble mucus gel is secreted by the gastric epithelium, and is believed to form an important barrier to acid injury. It is postulated that Helicobacter pylori can alter pH gradients by damaging the mucus layer, but no data on pH gradients in vivo in patients with H. pylori gastritis have been published. We aimed to construct a map of mucus-bicarbonate layer pH gradients in health and disease. Fourteen healthy asymptomatic volunteers (mean age, 46 yr) and 14 symptomatic patients with non-ulcer dyspepsia (NUD) (mean age, 46 yr) were studied. A flexible pH microelectrode was passed through the biopsy channel of an endoscope; luminal readings and three mucosal surface pH readings were obtained from each of five specific gastric sites (fundus greater curve, body greater curve, antrum greater curve, antrum lesser curve, and antrum anterior wall) using standardized methodology. Gradients at each site were calculated (mean juxta mucosal pH minus luminal pH); pH electrode accuracy was tested in standard buffer solutions. Biopsies were obtained from each site to assess for H. pylori status. Among asymptomatic volunteers, 21% had H. pylori; in NUD, 50% were infected. There was a significant association between H. pylori and histological gastritis at each site. The overall mean (+/- SE) pH gradients in H. pylori-positive and negative cases were similar, being 5.35 (+/- 0.06) and 5.26 (+/- 0.07), respectively. There was also no significant correlation between the histological gastritis score and the pH gradient at each gastric site. The pH gradients in healthy subjects (mean 5.31) and NUD (mean 5.29) were not significantly different. We conclude that pH gradients appear to remain stable throughout the stomach in healthy subjects and NUD, independent of H. pylori gastritis. PMID- 1595646 TI - Effect of sucralfate on the degradation of human gastric mucus by Helicobacter pylori protease and lipases. AB - Among the factors implicated in the weakening of mucus perimeter of gastric mucosal defense is Helicobacter pylori, the pathogenic action of which appears to be exerted through the elaborated protease and lipase enzymes. We present evidence that the activities of these enzymes are inhibited by an antiulcer agent, sucralfate. The grown colonies of bacteria were washed with saline, filtered through sterilization filter, and the filtrate used as the enzyme source. In the absence of sucralfate, the H. pylori protease caused extensive degradation of human gastric mucus protein, whereas free fatty acids, glycerol monooleate and lysophatidylcholine, were produced by the action of H. pylori lipase and phospholipase A enzymes. Introduction of sucralfate to the incubation systems led to the reduction in the rate of mucus protein and lipid degradation. The rate of proteolysis inhibition was proportional to sucralfate concentration up to 90 micrograms/ml, at which point a 32.5% reduction in mucus degradation was obtained, whereas the maximum inhibition of lipase (35.5%) and phospholipase A (48%) activities occurred at sucralfate concentration of 200 micrograms/ml. The results demonstrate that sucralfate is capable of counteracting in vitro the mucolytic activity of H. pylori toward human gastric mucus proteins and lipids. PMID- 1595647 TI - Endoscopic approach to pancreatic duct calculi and obstructive pancreatitis. AB - Twelve patients with chronic pancreatitis and obstructing pancreatic calculi underwent endoscopic retrograde cholangiopancreatography and attempted pancreatic stone extraction. This procedure, utilizing conventional stone baskets and balloons, as well as extracorporeal or laser lithotripsy in a subset, was ultimately successful in 11 of 12 patients. Nine of the 10 patients with relapsing pancreatitis have not had a symptomatic flare at a mean follow-up of 17 months. In contrast, neither of the patients who presented with chronic pain had convincing symptomatic improvement. The authors conclude that endoscopic removal of pancreatic duct calculi deserves further investigation in the treatment of relapsing attacks of chronic pancreatitis. PMID- 1595648 TI - Evaluation of severity in patients with acute pancreatitis. AB - We compared the multiple organ system failure (MOSF) score, the Acute Physiologic and Chronic Health Evaluation (APACHE) II, and Ranson and Imrie scores for their predictive value in evaluating severity of acute pancreatitis. Of the 259 patients, 73 (28%) had severe disease. Fifty-two (20%) patients had organ system failure (OSF) on admission, and 59% of patients with severe disease had OSF. Shortly after admission, only MOSF and APACHE II scores were available, and in patients with severe disease, these predictions were correct in 64% and 60%, respectively. Forty-eight hours later, the MOSF score was the most sensitive, and correctly predicted outcome in 67% of patients, compared with about 60% for other scores. Of four scoring systems, only MOSF and APACHE II scores allowed repetitive assessment to monitor the course of the disease. MOSF score is organ specific and may be better than APACHE II in reflecting disease activity. Our results suggest that the MOSF score is valuable in early identification and close monitoring of high risk patients and in deciding on therapy in these patients. PMID- 1595649 TI - Drug-responsive chronic segmental colitis associated with diverticula: a clinical syndrome in the elderly. AB - This report reviews the clinical presentation, endoscopic, radiologic, and pathologic features, and response to therapy in eight patients more than 60 yr old who presented with segmental chronic active colitis associated with sigmoid diverticula. The finding of colitis limited to the sigmoid colon in an area of multiple diverticula with no associated features of Crohn's disease, the age at onset, the response to therapy, and the benign course all suggest a distinctive form of inflammatory bowel disease in these patients. PMID- 1595650 TI - Fecal lysozyme: an unreliable marker for colorectal cancer. AB - High levels of lysozyme have been reported to be present in the feces of patients with colorectal cancer. It has been suggested that fecal lysozyme could prove useful in the early detection of colorectal cancer, but that further work is needed. The present investigation reports on the measurement of fecal lysozyme in 23 colorectal cancer patients and 39 healthy controls. The mean fecal lysozyme level for the cases was 13.3 +/- 2.8 micrograms/g stool compared with 12.5 +/- 2.6 micrograms/g stool for the controls. The median level for the cases was 8.7 micrograms/g stool compared with 6.6 micrograms/g stool for the controls. Forty three percent of the cases and 31% of the controls had fecal lysozyme levels above 10 micrograms/g stool. None of these differences were statistically significant. The results of this study indicate that fecal lysozyme would be of no use in the early detection of colorectal cancer. PMID- 1595651 TI - Large hiatal hernias, anemia, and linear gastric erosion: studies of etiology and medical therapy. AB - Patients with large diaphragmatic hiatal hernias occasionally manifest severe iron deficiency anemia. The etiology is believed to be that of small erosions at the waist of the hernia which bleed slowly. Our study attempts to determine the incidence of this condition in clinical practice, and whether acid plays a role in the pathophysiology. Sixteen such patients were identified prospectively in a series of 5219 consecutive patients (0.31%) accrued over a 5-yr interval. Anemia was the presenting feature, rather than symptoms of gastroesophageal reflux disease. The erosions were endoscopically identified and biopsied. Anemia was treated and recurrence was prevented for a mean of 24.6 months with long-term iron replacement. Of eight patients treated with iron alone, four were willing to undergo follow-up endoscopy. Of these four, none demonstrated healing. Three of these nonhealers and eight additional patients were treated with both iron and H2 antagonists. Thus, 11 patients were treated with H2 antagonists and iron, whereas four patients were treated with iron alone. At 6 wk, reendoscopy showed healing of the erosions in seven of 11 patients on H2 antagonists, but in none of those treated with iron alone (p less than 0.05). The anemia was corrected in all patients with iron therapy. We conclude that 1) gastric acid appears to have some role in the pathogenesis of this lesion; 2) short-term therapy with H2-receptor antagonists promote healing of the erosions; and 3) long-term iron therapy alone is adequate for initial and maintenance therapy of the anemia. PMID- 1595652 TI - The rim sign: the ghostly portender of acute cholecystitis. PMID- 1595654 TI - Gastric lesions in the excluded gastric segment undetected by endoscopy or radiography in patients status post vertical banded gastroplasty. AB - A patient had two surgical revisions and another patient had one surgical revision of a vertical banded gastroplasty because of intraoperative findings of gastric ulceration, incomplete penetration, and transmural penetration of the silicone band. Preoperative esophagogastroduodenoscopy in all three cases and an upper gastrointestinal series in two of the cases failed to demonstrate these lesions, because the lesions were located in the surgically excluded gastric segment. These reports demonstrate that a normal upper gastrointestinal series or panendoscopy in a patient after vertical banded gastroplasty does not exclude significant lesions in the endoscopically inaccessible, excluded gastric segment, and that it may be necessary to perform a laparotomy on a severely symptomatic patient even when an endoscopy is normal. PMID- 1595653 TI - Prevalence of gallbladder polyps among apparently healthy Japanese: ultrasonographic study. AB - The prevalence of gallbladder polyps was investigated in apparently healthy Japanese who underwent abdominal ultrasonography as part of their health screening examination. The polyps found were differentiated from gallstones, adenomas, or carcinomas as much as possible, and were considered to be cholesterol polyps. The prevalence of such gallbladder polyps was higher among males in every decade of age evaluated. The subjects with gallbladder polyps were more obese than the control group without gallbladder polyps, on abdominal ultrasonograms. The prevalence of gallbladder polyps rose in accordance with a rise in obesity index. At each range of obesity index, the prevalence of gallbladder polyps was higher among males. The prevalence of gallbladder polyps was highest among the middle-aged (40- and 50-yr-old) males, similar to the curve of the obesity index. In females, the obesity index increased with age, with no accompanying rise in the prevalence of gallbladder polyps. These data suggest that obesity contributes to the formation of cholesterol polyps of the gallbladder. PMID- 1595655 TI - A case of diversion colitis treated with 5-aminosalicylic acid enemas. AB - An 85-yr-old female presented with diversion colitis after surgery with a resultant colostomy and excluded rectal segment. Treatment with 5-aminosalicylic acid (Rowasa) enemas resulted in both endoscopic and histological resolution. This is the first case of diversion colitis treated with 5-aminosalicylic acid enemas. PMID- 1595656 TI - Menetrier's disease: evolution of disease under histamine-2 receptor antagonists. AB - A 33-yr-old man, with known peptic disease, developed giant thickening of the gastric mucosa and hypoproteinemia. Serial endoscopic and x-ray examinations of the upper gastrointestinal tract were available before and after the development of Menetrier's disease. In a 1-yr interval, erosive gastritis developed in a normal gastric mucosa, which was followed a few months later by hypoproteinemia. The patient developed the disease while being treated with histamine-2 receptor antagonists. PMID- 1595657 TI - Intractable gastroparesis: treatment with percutaneous fluoroscopically guided gastrostomies. AB - Gastroparesis is a relatively uncommon disorder which may develop in some patients with diabetes mellitus, or after gastric surgery. It is often manifested by intractable nausea and vomiting, leading to malnourishment and poor blood sugar control in the diabetic patient. We describe such a patient who was diabetic, and who also had a previous vagotomy and pyloroplasty. Currently acceptable pharmacologic treatment was unsuccessful. The patient's problems were successfully treated, however, by double-percutaneous fluoroscopically guided gastrostomy catheter insertions. One of the gastrostomy catheters was placed in the gastric fundus and linked externally to a second (feeding) catheter that had been placed previously at the duodenal-jejunal flexure. The patient has remained symptom free in the 14 months since the procedure. Other available treatments are discussed, and the authors recommend that this simple and safe method be considered in treating severe intractable gastroparesis. PMID- 1595658 TI - Jejunal diverticulitis. AB - A case of perforated jejunal diverticulitis in a 44-yr-old man is described and the literature is reviewed. Jejunal diverticulosis occurs in 0.07% to 2% of the population. Enteroclysis is the best diagnostic test. Diverticulitis with perforation is rare and is associated with high mortality. Treatment is surgical resection of the involved segment. Other complications are bacterial overgrowth, obstruction, and acute hemorrhage. Several theories to explain the physiopathogenesis of the diverticula formation may relate to manometric or histological abnormalities of the small bowel. PMID- 1595659 TI - Treatment of granular cell tumor of the esophagus by endoscopic injection of dehydrated alcohol. AB - Granular cell tumor of the esophagus (GCTE) is a rare and mostly benign neoplasm. Its etiology is unknown and its histogenesis is uncertain. It is usually an incidental finding, detected during esophagogastroduodenoscopy. In symptomatic cases, or when the lesions are more than 1 cm in diameter, the treatment of choice has been local resection. Asymptomatic patients or tumors smaller than 1 cm are followed endoscopically. We describe a case of GCTE successfully treated by endoscopic injection of dehydrated ethyl alcohol. To our knowledge, it is the first time that such a tumor was treated by this accessible and low-cost technique. PMID- 1595660 TI - Intrarectal tear from water skiing. AB - We report a case of intrarectal tear and hemorrhage after a fall while water skiing. The injury resulted from rectal douche, or jet enema, which is dangerous because of the high pressure of the water jets forced into the rectum. The patient, a middle-aged woman, had colonoscopy, which revealed a deep rectal laceration. During subsequent colostomy, a full-thickness laceration and an extensive pelvic and retroperitoneal hematoma with some free blood were found. The patient's recovery was uneventful, and she subsequently had reanastomosis of her colostomy. We recommend protective apparel to prevent these injuries. PMID- 1595661 TI - Propofol and cholestatic pruritus. AB - Hepatic cholestatis is frequently associated with pruritus. This pruritus is often intractable and resistant to conventional treatment. We treated three patients with intractable cholestatic pruritus with subhypnotic doses of propofol, a new intravenous anesthetic induction agent. All patients rapidly became itch- and scratch-free for a period of 60-90 min. No sedation occurred; no other side effects were observed. PMID- 1595662 TI - Magnesium-induced diarrhea: more firm data on loose stools. PMID- 1595663 TI - Alcohol hepatotoxicity: a genotypic predisposition? PMID- 1595664 TI - Onions and heartburn. PMID- 1595665 TI - Intestinal permeability in HIV infection: proper controls are necessary. PMID- 1595666 TI - Cisapride and gastroesophageal reflux disease. PMID- 1595667 TI - Long-term omeprazole monotherapy is ineffective against Helicobacter pylori infection. PMID- 1595668 TI - Thromboembolism as the first symptom of Menetrier's disease. PMID- 1595669 TI - Different contrast agents and development of pancreatitis after endoscopic retrograde pancreatography. PMID- 1595670 TI - Different contrast agents and development of pancreatitis after endoscopic retrograde pancreatography. PMID- 1595671 TI - Different contrast agents and development of pancreatitis after endoscopic retrograde pancreatography. PMID- 1595672 TI - Alcohol measuring scales may influence conclusions about the role of alcohol in human immunodeficiency virus (HIV) risk and progression to acquired immunodeficiency syndrome (AIDS). AB - In an effort to clarify the role of alcohol in human immunodeficiency virus (HIV) risk and progression to acquired immunodeficiency syndrome (AIDS), the author reviewed the method of measuring alcohol consumption across 10 studies published from 1986 through 1990. When the reports in which the association between alcohol and HIV has been evaluated in at-risk groups are compared, the role of alcohol remains unclear. Although there are fewer reports available for analysis, the role of alcohol in the progression of the disease to AIDS has been consistent in indicating that there is no effect of alcohol use. However, the research in both of these areas has utilized different methods to measure alcohol use. There are data relevant to the association between alcohol and HIV that indicate that the estimate of alcohol use is at least partially dependent on the type of measuring instrument used. The application of different measures of alcohol use may have led to different conclusions regarding the role of alcohol in HIV. With regard to the role of alcohol in the progression of the disease to AIDS, even in the consistent findings that alcohol does not lead to progression of the disease to AIDS, a more sensitive measure of alcohol use might yield different results. PMID- 1595673 TI - Independent protective effect of lactation against breast cancer: a case-control study in Japan. AB - A case-control study was carried out to assess the risk of breast cancer associated with breast feeding in Japan. The data were obtained in a hospital based case-control study of 521 women with breast cancer and 521 controls from January 1988 to December 1989. Statistical adjustment for potential confounders as well as a likelihood ratio test for linear trend was done by unconditional logistic regression. Compared with parous women who had never breast-fed, women with a positive history of breast feeding had an odds ratio of breast cancer of 0.62 (95% confidence interval 0.37-1.04). The trend of decreasing risk with increasing average months of breast feeding was statistically significant (chi 2 trend = 4.5, p less than 0.05), while it was was nonsignificant for the number of breast-fed children borne. Among premenopausal women, a significant linear relation with a log-transformed term of average months of breast feeding was noted, regardless of the age of the woman at first full-term pregnancy and parity (chi 2 trend = 5.3, p less than 0.05). The risk was the lowest among premenopausal women who had ever lactated for 7-9 months (adjusted odds ratio = 0.39, 95% confidence interval 0.15-0.97). These findings suggest that lactation has an independent protective effect against breast cancer in Japanese women. PMID- 1595674 TI - The association of cutaneous malignant melanoma and fluorescent light exposure. AB - Data are presented from an interview case-control study (583 cases and 608 controls), performed in southern Ontario, Canada, from October 1984 to September 1986, on the association of cutaneous malignant melanoma with exposure to fluorescent light. Males showed a significant trend with cumulative years of occupational exposure and with various indices of exposure to domestic fluorescent light. The risk was more pronounced for lesions on the arms and for superficial spreading melanomas. There was no consistent association in females. These effects were similar when adjusted for other major risk factors for melanoma, including the amount of time spent outdoors occupationally. Comparisons of melanoma cases interviewed before or after diagnosis revealed no evidence of rumination bias. Comparisons of sample data from the same cases and controls by interview and mail questionnaire showed reasonable levels of reliability with no evidence of recall bias. A small sample of subjects was also selected for exposure validation with employers; this revealed very accurate recall of occupational exposure. On the basis of these results, previous epidemiologic studies, and clinical and animal evidence, the authors conclude that fluorescent light exposure remains a potential risk factor for melanoma. PMID- 1595675 TI - Smoking and risk of leukemia. AB - The relation between tobacco use and leukemia was evaluated in a population-based case-control study of 578 white men with leukemia and 820 controls conducted in Iowa and Minnesota during 1981-1984. Risks were significantly elevated for all leukemia (odds ratio (OR) = 1.4) and chronic lymphocytic leukemia (OR = 1.6) for both tobacco users and cigarette smokers. There were significantly elevated risks for cigarette smokers of longest duration for all leukemia (OR = 1.6), chronic myelogenous leukemia (OR = 3.3), and chronic lymphocytic leukemia (OR = 1.6). Thus, the findings of this study provide additional support for an association between smoking and the risk of several types of leukemia. PMID- 1595676 TI - Body mass index and lung cancer risk. AB - The relation of body mass index, based on self-reported weight 5 years prior to diagnosis, to lung cancer was investigated in 3,607 lung cancer cases and 9,681 controls interviewed in a hospital-based case-control study in eight US cities between 1981 and 1990. Separate analyses were carried out by smoking status and by sex. After adjustment for covariates, odds ratios for lung cancer by levels of body mass index, taking greater than or equal to 28 as the referent, showed an increasing linear trend with decreasing body mass index for current smokers and ex-smokers of both sexes and for female never smokers. These results are consistent with findings of a number of prospective studies. Further studies are needed to determine whether the association of low body mass and lung cancer is due to factors associated with leanness or to a biologic effect of leanness itself. PMID- 1595677 TI - Head trauma and the risk of Alzheimer's disease. AB - A population-based case-control study of the association between head trauma and Alzheimer's disease was conducted in the Netherlands from 1980 to 1987. The study comprised 198 patients with clinically diagnosed early onset Alzheimer's disease and 198 age- and sex-matched population controls. Adjusted for sex, age, family history of dementia, and education, the odds ratio of a history of head trauma with loss of consciousness was 1.6 (95% confidence interval (CI) 0.8-3.4). The odds ratio for men was 2.5 (95% CI 0.9-7.0), and that for women was 0.9 (95% CI 0.3-2.8). The increase in odds ratio was limited to head trauma that occurred within the period of 10 years prior to the onset of dementia (odds ratio = 10.0; 95% CI 1.0-96.8). There was no evidence of effect modification by family history of dementia as measured on a multiplicative scale. However, the power to show interaction may have been low in this study. The authors' findings are compatible with the view that head trauma may be implicated in Alzheimer's disease, with a short lag time between the head trauma and the first symptoms of disease. The association needs to be confirmed in a prospective follow-up study to fully exclude the possibility of recall bias. PMID- 1595678 TI - The influence of aging on plasma sex hormones in men: the Telecom Study. AB - From April 1985 to July 1987, 1,408 healthy white men aged 20-60 years in Paris, France, recruited on an occupational basis, underwent a physical examination and measurements of plasma sex hormones in a cross-sectional study. Both total testosterone and estradiol showed a significant stepwise decrease with age (p less than 0.001) starting in the early adult years, while estrone did not vary. These relations of testosterone and estradiol with age remained significant after adjustment for body mass index, subscapular skinfold, and tobacco and alcohol consumptions, and they were not modified by exclusion of the men who reported chronic disease. Both the mechanism for the early decrease in testosterone and its clinical significance merit further investigation. PMID- 1595679 TI - Major depressive disorder and dysthymia in young adolescents. AB - A two-stage epidemiologic study conducted between 1986 and 1988 in the southeastern United States investigated the frequency of major depressive disorder and dysthymia in 12-14 year olds. In stage one, the Center for Epidemiologic Studies Depression Scale, a life event schedule, and a family cohesion scale were administered to a community sample of 3,283 adolescents. In stage two, 488 mother-child pairs were interviewed utilizing the Schedule for Schizophrenia and Affective Disorders in School Age Children. Although mean Center for Epidemiologic Studies Depression Scale scores were significantly higher in females (25.60) than in males (19.50), prevalence estimates based on a summary of mother and child symptom reports for Diagnostic and Statistical Manual of Mental Disorders, Third Edition, major depressive disorder were similar: 9.04% in males and 8.90% in females. The prevalences of dysthymia were 7.98% in males and 5.00% in females. Previous investigations have reported lower rates and a female preponderance of major depression. Disagreement between mothers and children regarding the presence of symptoms may explain this contradiction. Significant odds ratios were found between major depression and not living with both natural parents (odds ratio (OR) = 3.89), undesirable life events (OR = 1.09), and perceived family cohesion (OR = 0.96). Not living with both natural parents (OR = 14.67) and socioeconomic status (OR = 0.44) were significant correlates of dysthymia. PMID- 1595680 TI - Childhood diabetes, epidemics, and epidemiology: an approach for controlling diabetes. World Health Organization DIAMOND Project Group on Epidemics. AB - The identification of the environmental factors causing insulin-dependent diabetes in children has remained elusive. However, evidence is rapidly accumulating that childhood diabetes exhibits epidemic patterns, much like that seen with an infectious disease. It is likely that within these epidemics the environmental determinants of disease will be found. Here the authors argue that the development of a surveillance system for early identification of epidemics plus field studies are needed to determine the etiology and mode of transmission of the disease. PMID- 1595681 TI - Approaches to the analysis of case-control studies of the efficacy of screening for cancer. AB - To an increasing extent, case-control studies are being undertaken to determine if use of early detection procedures is associated with reduced mortality from cancer. The authors recommend that in such studies the analysis focus on screening activity in cases that occurs during an interval prior to diagnosis in which the cancer is believed to be detectable and still curable and to a corresponding time period in controls. This approach places a heavy burden on the investigator to estimate accurately the period during which the tumor ought to be detectable using the test in question and to sort out reliably tests done in response to signs or symptoms of the cancer from screening tests per se. Nonetheless, the authors feel that it offers the greatest ability to discern a true benefit of screening, while minimizing the numerous potential biases that can be present in this type of study. PMID- 1595682 TI - The standardized mortality ratio and life expectancy. AB - This paper develops a theoretical relation between the standardized mortality ratio (SMR) and the expected years of life and establishes a regression equation for easy conversion between these two statistics. The mathematical expression of the derived relation is an approximation, requiring an assumption of constant age specific mortality ratios. It underestimates the "true" value calculated based on life table technique when the age-specific mortality ratios increase with age. This equation provides a conservative method to estimate the expected years of life for cohort mortality studies and facilitates an assessment of the impact of work-related factors on the length of life of the worker. It also allows one to convert the SMR to life expectancy in smaller studies whose sole objective is to determine the SMR in a working population. A 1% decrease (or increase) in the standardized mortality ratio will result in 0.1373 years increased (or decreased) life expectancy based on white male data for the US population. Furthermore, with data from 14 large oil refinery and chemical worker cohorts of white males, the "derived" expected years of life based on the regression equation closely predicts the corresponding value calculated using a standard life table technique. This statistical equation is expected to have practical applications when used in conjunction with the SMR to provide an approximate measure of life expectancy, a term and statistic familiar to most lay people. PMID- 1595683 TI - Re: "Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland". PMID- 1595684 TI - Re: "Use of electric blankets and risk of postmenopausal breast cancer". PMID- 1595685 TI - Re: "Tobacco smoke exposure and pregnancy outcome among working women: a prospective study at prenatal care centers in Orebro County, Sweden". PMID- 1595686 TI - Congenital defects and electric bed heating in New York State: a register-based case-control study. AB - Exposure to 60-cycle electromagnetic fields has been hypothesized to be a cause of childhood cancer and congenital defects. Because electric bed heaters are a major source of variation in electromagnetic field exposure in the population, the authors conducted a case-control study in 1988-1989 to examine the relations between congenital defects and the use of electric blankets and heated waterbeds. Cases were identified by the New York State Congenital Malformations Registry as babies with cleft palate (n = 121), cleft lip with or without cleft palate (n = 197), born in 1983-1984, and anencephalus and spina bifida (n = 224), born in 1983-1986, all to upstate New York residents. Controls were selected at random from birth registrations individually matched to cases by maternal race, age, home county, month of last menses, and child's sex. Information on periconceptional electric blanket and heated waterbed use as well as known and suspected risk factors for defects was obtained from questionnaires mailed to the mothers. Matched odds ratio estimates and 95% confidence intervals (CIs) for electric blanket use relative to nonuse were 0.8 (95% CI 0.3-2.1) for cleft palate, 0.7 (95% CI 0.3-1.3) for cleft lip, and 0.9 (95% CI 0.5-1.6) for neural tube defects. The respective odds ratios for heated waterbed use were nearly identical to these. Adjustment for potential confounding factors (maternal education, vitamin use, smoking) and stratification by season of conception and bed heat control setting had no meaningful effect on odds ratios. These results suggest that 60-cycle fields do not cause neural tube and oral cleft defects. PMID- 1595687 TI - Changing epidemiology of hepatitis B in Italy: public health implications. AB - In Italy, a dramatic decline of hepatitis B infection occurred in recent years as a result of nonmedical and medical factors. The national type-specific surveillance system shows that the age of maximum incidence changed from early childhood, when the risk of becoming a chronic carrier after infection is very high, to late adolescence. Data of several seroepidemiologic studies are consistent with this picture, but could not be compared with previous data on similar age groups. In 1981, a seroepidemiologic study on a national sample of 5,005 recruits showed a high prevalence of serologic markers of hepatitis B infection among young adults in Italy. In 1990, the authors replicated that original study on a national sample of 4,993 recruits. The adjusted prevalence of hepatitis B core antibodies among Italian male recruits dropped from 16.8% to 5.8% in 9 years. The authors anticipate a substantial reduction in the rate of production of chronic carriers and the rates of liver cirrhosis and primary liver carcinoma in Italy in the next decades. Vaccination campaigns, especially if combined with nonimmunologic preventive measures, will further reduce the rate of hepatitis B infection in Italy. PMID- 1595688 TI - Selection of controls in case-control studies. I. Principles. AB - A synthesis of classical and recent thinking on the issues involved in selecting controls for case-control studies is presented in this and two companion papers (S. Wacholder et al. Am J Epidemiol 1992;135:1029-50). In this paper, a theoretical framework for selecting controls in case-control studies is developed. Three principles of comparability are described: 1) study base, that all comparisons be made within the study base; 2) deconfounding, that comparisons of the effects of the levels of exposure on disease risk not be distorted by the effects of other factors; and 3) comparable accuracy, that any errors in measurement of exposure be nondifferential between cases and controls. These principles, if adhered to in a study, can reduce selection, confounding, and information bias, respectively. The principles, however, are constrained by an additional efficiency principle regarding resources and time. Most problems and controversies in control selection reflect trade-offs among these four principles. PMID- 1595689 TI - Selection of controls in case-control studies. II. Types of controls. AB - Types of control groups are evaluated using the principles described in paper 1 of the series, "Selection of Controls in Case-Control Studies" (S. Wacholder et al. Am J Epidemiol 1992;135:1019-28). Advantages and disadvantages of population controls, neighborhood controls, hospital or registry controls, medical practice controls, friend controls, and relative controls are considered. Problems with the use of decreased controls and proxy respondents are discussed. PMID- 1595690 TI - Selection of controls in case-control studies. III. Design options. AB - Several design options available in the planning stage of case-control studies are examined. Topics covered include matching, control/case ratio, choice of nested case-control or case-cohort design, two-stage sampling, and other methods that can be used for control selection. The effect of potential problems in obtaining comparable accuracy of exposure is also examined. A discussion of the difficulty in meeting the principles of study base, deconfounding, and comparable accuracy (S. Wacholder et al. Am J Epidemiol 1992;135:1019-28) in a single study completes this series of papers. PMID- 1595691 TI - Psychopathology and attrition in the epidemiologic catchment area surveys. AB - This analysis shows the effect of sociodemographic variables and psychopathology on attrition in a 1-year follow-up of 10,167 household-residing respondents, aged 18-64 years, from four sites of the National Institute of Mental Health Epidemiologic Catchment Area Program. Attrition is defined in two ways: failure to locate (n = 1,035) and refusal to participate (n = 1,010). As compared with 8,122 respondents successfully interviewed after 1 year, those who are not located are more likely to be male, Hispanic, young, and unmarried. Refusers are older and more likely to be married and to have lower educational attainment than those successfully reinterviewed. After adjusting for sociodemographic variables, psychopathology had a small to moderate effect on attrition. Panic and depression were associated with failure to locate, but no diagnoses, or selected symptoms, were strongly or significantly associated with refusal to participate in the second wave. PMID- 1595692 TI - Re: American Journal of Epidemiology and Fruits and Vegetables. PMID- 1595693 TI - Re: "Exposure to residential electric and magnetic fields and risk of childhood leukemia". PMID- 1595694 TI - Predictors of smoking cessation: the Framingham Study. AB - The relation of demographic, behavioral, and health-related variables to smoking cessation was studied in 1,178 women and 1,506 men cigarette smokers enrolled in the Framingham Heart Study. Smoking cessation was defined as abstinence from all tobacco products for at least 1 year. Proportional hazard models were used to identify baseline variables associated with long-term cessation. In order to identify factors predictive of cessation in the following 2 years, logistic regression models on person-examination data were used. Recent hospitalization and development of coronary heart disease were predictive of smoking cessation, while diagnosis of cancer or changes in pulmonary function were not. Overall, women were as likely to quit as men; however, women who smoked heavily were the least likely to quit. Secular trends were noted in men only; men were more likely to quit after the release of the 1964 Surgeon General's report on smoking. The relation of illness development and sex to smoking cessation should be considered in developing smoking cessation programs. PMID- 1595695 TI - Race/ethnicity and other risk factors for gestational diabetes. AB - Although gestational diabetes is estimated to complicate between 1% and 5% of pregnancies, there are only limited data on the role of race/ethnicity as well as other risk factors in the development of this disorder. Epidemiologic characteristics of gestational diabetes were assessed in an ethnically diverse cohort of 10,187 women who had undergone standardized screening for glucose intolerance and who delivered a singleton infant at the Mount Sinai Medical Center in New York City between January 1987 and December 1989. The overall prevalence of gestational diabetes was 3.2%. Multiple logistic regression analysis showed excess risks for Oriental women, Hispanics born in Puerto Rico or elsewhere outside the United States, women from the Indian subcontinent and the Middle East, older mothers, heavier women, those with a positive family history of diabetes, women with a history of infertility, and those who delivered on the clinic service. These data suggest that, after controlling for traditional risk factors (maternal age, prepregnancy weight, and a family history of diabetes), Orientals, first generation Hispanics, women from the Indian subcontinent and the Middle East, those with a history of infertility, and low socioeconomic status women are at an increased risk for gestational diabetes. PMID- 1595696 TI - Principal lifetime occupation and cognitive impairment in a French elderly cohort (Paquid). AB - The purpose of the present study was to examine the relation between principal lifetime occupation and cognitive performance with the initial data collected (1988-1989) in a cohort of 3,777 community residents of the area of Bordeaux, France, aged 65 years and older. Subjects were considered as cognitively impaired if they scored under 24 on the French version of the mini-mental state examination. Cognitive impairment was found to vary significantly across the different occupational categories. Results of the logistic regression show that age, sex, and educational level are significantly related to cognitive impairment. Moreover, after controlling for these and other covariates, farmworkers (odds ratio (OR) = 6.1, 95% confidence interval (CI) 3.3-11.4), farm managers (OR = 2.9, 95% CI 1.6-5.1), domestic service employees (OR = 2.8, 95% CI 1.5-5.1), and blue-collar workers (OR = 2.5, 95% CI 1.4-4.4) had a higher risk of cognitive impairment than did subjects who had an intellectual occupation. Follow up of the cohort will permit precise determination of the role of principal lifetime occupation in subsequent cognitive deterioration. Occupational status should be taken into consideration when studying brain aging. PMID- 1595698 TI - Continuous quality improvement in chronic disease: a computerized medical record enables description of a severity index to evaluate outcomes in end-stage renal disease. AB - We have previously derived an index, based on retrospective data, for mortality in patients with end-stage renal disease (ESRD) treated by dialysis and transplantation. We used this index to calculate probability of death and rates of hospitalization, two measures of severity of illness, for 436 patients enrolled in our ESRD program after the original index was derived. Applied when ESRD treatment was initiated, it predicted future mortality and hospitalization rates. We then analyzed clinical characteristics, including variables in the predictive model, in all 718 patients enrolled in 3-year cohorts from 1976 to 1989. Over time, there was trend toward enrolling patients with a higher likelihood of dying, ie, more severely ill. The severity index facilitated description of the patients and their changing characteristics over time, and proved useful in comparing the degree of illness in different population groups. PMID- 1595697 TI - The risk of alcohol abuse and dependence in adulthood: the association with educational level. AB - In this analysis of prospectively gathered data, the authors sought to estimate the degree to which risk of alcohol abuse and dependence might be elevated among adults who attended but did not complete high school and among those who attended college without earning a degree. Study subjects were selected in 1980-1984 by taking probability samples of adult household residents at five sites of the Epidemiologic Catchment Area Program: New Haven, Connecticut; Baltimore, Maryland; St. Louis, Missouri; Durham-Piedmont, North Carolina; and Los Angeles, California. At baseline, participants completed standardized interviews that measured sociodemographic variables and assessed whether they had met diagnostic criteria for currently or formerly active alcohol abuse-dependence syndromes. The interviews were readministered 1 year later to identify incident cases among the 13,673 participants. After subjects were sorted into risk sets by age and residence census tract and after persons with a prior history of alcohol abuse or dependence were excluded, there were in 156 risk sets 160 incident cases and 526 subjects at risk for future occurrence of alcohol syndromes. Compared with adults who had earned a college degree, those who had attended high school without completion were at increased risk (relative risk (RR) = 6.23, 95 percent confidence interval (CI) 2.41-16.09) as were adults who had attended college without earning a degree (RR = 3.25, 95 percent CI 1.36-7.76). In contrast, risk of alcohol disorders among adults with a high school diploma but no college was not reliably greater than the level of risk for those with a college degree (RR = 1.88, 95 percent CI 0.79-4.47). PMID- 1595699 TI - The impact of diagnosis-related groups on the cost of hospitalization for end stage renal disease patients at Rhode Island Hospital from 1987 to 1990. AB - The introduction of diagnosis-related groups (DRGs) for the reimbursement of hospital costs in the Medicare population made no provisions to identify end stage renal disease (ESRD) patients. To assess the impact of the DRGs on ESRD patients, we prospectively evaluated all hospitalizations (901) at the Rhode Island Hospital from July 1987 through April 1990 among a chronic hemodialysis population of 587 patients. The complied data on length of hospital stay, cost per day, and total cost were compared with the accepted allowances as defined by the DRG codes assigned to the admissions. The mean values and comparisons were length of stay, 10.2 +/- 21 days (ESRD) versus 9.7 +/- 3.6 days (DRGs), P = 0.44; cost per day, $1,240 +/- $685 (ESRD) versus $671 +/- $897 (DRGs), P = 0.0001; and total cost, $9,660 +/- $17,170 (ESRD) versus $6,815 +/- $8,872 (DRGs), P = 0.0001, a difference of $2,275 per admission. The increase in daily, and thus total, costs was primarily due to the use of supplies, medications, laboratory procedures, and transfusion services. It appears from our data that the DRGs do not adequately reflect the cost of caring for ESRD patients with the same DRGs as non-ESRD patients because of increased demand for ancillary services. If these observations are confirmed, a reevaluation of the DRG process as it relates to ESRD patients is warranted. PMID- 1595700 TI - Long-term follow-up of non-systemic lupus erythematosus glomerulonephritis in patients with hereditary angioedema: report of four cases. AB - Hereditary angioedema (HAE) is characterized by a deficiency in C1 inhibitor protein (C1 INH) and by clinical symptoms of episodic swelling of subcutaneous or mucosal tissue. It has rarely been reported in association with non-systemic lupus erythematosus (SLE) glomerulonephritis (GN). A recent report of two cases indicates the prognosis to be poor, with both patients progressing to chronic renal failure 8 and 20 years after diagnosis. This report describes the 5-year follow-up of a previously unreported case of an 8-year-old boy with HAE and non SLE membranoproliferative glomerulonephritis (MPGN). The patient developed macroscopic hematuria, azotemia, and a vasculitic rash. Treatment included prednisone and cyclophosphamide, resulting in clinical improvement. The present report also summarizes the long-term follow-up of three previously reported cases of HAE and non-SLE GN, 25, 16, and 10 years after their initial presentation. Patients monitored for 25 and 16 years had MPGN and normal renal function and received no therapy. The third patient, monitored for 10 years, had segmental MPGN. This patient presented with urinary abnormalities and, after treatment with prednisone, had improvement in her hematuria. None of these four patients developed chronic renal failure. These observations indicate a variable outcome in patients with HAE and non-SLE GN. PMID- 1595701 TI - Safety and efficacy of long-term treatment of secondary hyperparathyroidism by low-dose intravenous calcitriol. AB - To assess the safety and efficacy of low-dose intravenous (IV) calcitriol therapy for the treatment of secondary hyperparathyroidism, 21 hemodialysis patients with amino-terminal parathyroid hormone (N-PTH) levels greater than 4 times normal were treated for 12 to 24 months in a prospective trial. The initial dose was 0.50 microgram, which was titrated every 3 months thereafter, as dictated by predialysis calcium, phosphorus, and N-PTH concentration. Dialysate calcium concentration was 1.5 mmol/L. Low-dose IV calcitriol decreased the N-PTH concentration to 48 +/- 6% and 29 +/- 5% of baseline following 12 and 24 months of therapy, respectively. The maximum dose of calcitriol was 0.92 +/- 0.11 microgram (0.50 to 2.25 micrograms). After 12 months of therapy, serum calcium increased from 2.22 +/- 0.04 to 2.41 +/- 0.03 mmol/L (8.9 +/- 0.2 to 9.7 +/- 0.1 mg/dL) without change thereafter. Baseline serum phosphorus was 1.44 +/- 0.09 mmol/L (4.5 +/- 0.3 mg/dL), and was unaltered by calcitriol therapy. Control of serum phosphorus was achieved with calcium-containing phosphate binders, except in three patients who were subsequently withdrawn from the study after 12 months because of persistent hyperphosphatemia due to noncompliance. We conclude that long-term, low-dose IV calcitriol is a safe and effective therapy for most hemodialysis patients with secondary hyperparathyroidism. In contrast to conventional dosing regimens, low-dose IV therapy does not necessitate the use of aluminum-containing phosphate binders and/or a low-calcium dialysate bath. PMID- 1595702 TI - Pulse oral calcitriol for the treatment of hyperparathyroidism in patients on continuous ambulatory peritoneal dialysis: preliminary observations. AB - A direct effect of calcitriol on the regulation of the secretion of parathyroid hormone (PTH) has been shown in vitro and in vivo. In patients with renal failure on maintenance hemodialysis, it has been shown that intravenous (IV) administration of calcitriol appears to be superior to continuous oral administration. This may be due to the higher levels of calcitriol obtained in blood with consequent improved delivery of calcitriol to peripheral target tissues including the parathyroid glands. However, IV administration of calcitriol, is not practical for patients with end-stage renal disease (ESRD) who are maintained on continuous ambulatory peritoneal dialysis (CAPD). The present studies were designed to investigate whether intermittent administration of large doses of calcitriol orally ("pulse therapy") could mimic the effects of IV calcitriol in hemodialysis patients and achieve suppression of PTH secretion. Studies were performed in five patients who had been maintained on CAPD for more than 6 months. After basal determinations of calcium, phosphorus, and PTH, therapy was begun with calcitriol administered orally in a dose of 5 micrograms given twice per week. Calcium carbonate was continued as a phosphate binder. Dialysate calcium concentration was 1.75 mmol/L (3.5 mEq/L). With this therapy, PTH levels decreased rapidly, and, after 4 to 6 weeks of therapy, reached values 60% lower than pretreatment values. Mean values for serum calcium did not change significantly (2.29 +/- 0.12 mmol/L [9.6 +/- 0.5 mg/dL] before treatment compared with 2.32 +/- 0.08 mmol/L [9.7 +/- 0.25 mg/dL] after therapy). Mean serum phosphorus was also unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595703 TI - Oxalate balance studies in patients on hemodialysis for type I primary hyperoxaluria. AB - Primary hyperoxaluria type I (PH1) always leads to end-stage renal failure (ESRF) due to deposition of calcium oxalate in the kidney. Regular dialysis therapy (RDT) can not overcome the excess production of oxalate, hence, systemic oxalate deposition occurs. The extent of tissue deposition and the rate at which oxalate accumulates influence the quality of life and survival of the patients. Therefore, an estimate of the oxalate balance needs to be made for patients on RDT. In this study, we suggest a simple model by which some of the main parameters of oxalate turnover can be assessed without using radioactive materials. Levels of oxalate, glycolate, and urea, and degrees of calcium oxalate saturation, were assessed on plasma ultrafiltrates from two patients with PH1, sampled before, at the end of a dialysis session, and over the entire interdialytic interval. In patients with PH1, oxalate increased linearly during the early phases and then the curve flattened at a concentration corresponding to approximately threefold saturation. The initial phase of the relationship was used to estimate generation rate of oxalate. The delayed phase was ascribed to the deposition of newly generated oxalate out of its miscible pool. Conversely, the relationship for glycolate and urea remained linear. This was also different from the values obtained in four patients with oxalosis-unrelated ESRF, whose oxalate levels increased linearly over the entire interdialytic interval. In the two patients with PH1, the overall oxalate generation was assessed at 4 to 7 mmol/d. The difference between generation and dialysis removal indicated that tissue deposition was greater than 50 mumol/kg body weight/d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595704 TI - Forecasting thrombosis of vascular access with Doppler color flow imaging. AB - A noninvasive technique, color Doppler flow imaging, was used to study the predictive value for future episodes of thrombosis in vascular access (polytetrafluoroethylene [PTFE] grafts and radial-cephalic fistulae) in a series of chronic hemodialysis patients. Patients with grafts were classified into three groups based on maximum constriction of the vascular access diameter: narrowing of greater than 50% (group I), narrowing of 30% to 50% (group II), and no narrowing or narrowing less than 30% (group III). More than half of the patients in group I suffered vascular access thrombosis within 6 months, while only 9% to 13% of patients in groups II and III had episodes of thrombosis during the same time interval. Decreased access volume flow (AVF) also correlated with episodes of thrombosis in these patients. No correlation could be demonstrated between recirculation and future thrombosis. No patient with a fistula had narrowing greater than 30% and none had vascular access thrombosis during the 6-month follow-up. PMID- 1595705 TI - Factors affecting renal allograft function in long-term recipients. AB - The natural history of renal allograft function in long-term recipients is not known. To characterize renal allograft function and the factors that affect it, we reviewed the records of all patients who received a renal allograft at the University of Wisconsin between 1965 and 1981 and selected those who had annual data on renal function for at least 10 years. We identified 155 patients--78 with living-related donors and 77 with cadaveric donors. All patients were adults receiving azathioprine and prednisone. Renal function was estimated by calculated creatinine clearances (Ccr), which correlated well with measured 24-hour creatinine clearances. The creatinine clearance data for each patient were plotted versus time. In 73% of patients, the creatinine clearance increased for several years before reaching a peak value. After the peak, the creatinine clearance declined in a linear manner. Stepwise regression analyses indicated that allografts from cadaveric donors had a greater increase in creatinine clearance from the value at year 1 to the peak than allografts from living related donors (0.35 +/- 0.25 v 0.21 +/- 0.23 mL/s [21.4 +/- 15.0 v 12.7 +/- 13.8 mL/min]; P less than 0.001). The average time to reach the peak value of creatinine clearance was longer in cadaveric allografts (6.8 +/- 3.5 v 4.6 +/- 4.0 years; P less than 0.001). Postpeak, the rate of decline in creatinine clearance was faster in cadaveric allografts than in living-related ones (0.06 +/ 0.05 v 0.04 +/- 0.04 mL/s/yr [3.50 +/- 2.99 v 2.55 +/- 2.16 mL/min/yr]; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595706 TI - Short-term hypothyroidism and vasopressin gene expression in the rat. AB - Hypothyroidism is associated with abnormalities in renal water handling, which include a delay in excretion of an acute water load, decreased urinary concentrating ability, and increased urine volume. In the present study, we investigated the role of vasopressin in aminotriazole-induced hypothyroidism by measuring vasopressin concentration in the plasma and pituitary along with vasopressin mRNA levels in the hypothalamus. After 5 weeks of aminotriazole treatment, L-thyroxine levels were significantly lower in the experimental animals (122 +/- 8 v 26 +/- 1 nmol/L [9.5 +/- 0.6 v 2.0 +/- 0.1 micrograms/dL]; P less than 0.001). Serum sodium (148 +/- 0.5 v 144 +/- 1.2 mmol/L [mEq/L]; P less than 0.01), and plasma osmolality (311 +/- 2.5 v 304 +/- 1.8 mmol/kg [mOsm/kg] H2O; P less than 0.05) were also lower in the experimental animals. There were no differences in plasma (1.9 +/- 0.4 v 1.5 +/- 0.2 pg/mL) or pituitary (1.5 +/- 0.4 v 1.5 +/- 0.2 microgram/pituitary) vasopressin levels. In addition, steady-state vasopressin mRNA levels were not different between the two groups (1,286 +/- 210 v 1,093 +/- 138 pg/hypothalamus). One week of L-thyroxine replacement resulted in significant increases in serum thyroxine levels without changes in the other variables measured. These results indicate that short-term hypothyroidism, which has been shown to exert substantial effects on renal function, causes only a modest central alteration in the plasma vasopressin-osmolality relationship, which occurs in the absence of detectable changes in vasopressin synthesis. PMID- 1595707 TI - Effect of glycine and hypertrophy on renal outer medullary hypoxic injury in ischemia reflow and contrast nephropathy. AB - Glycine preserves tubular cell integrity under hypoxic and toxic conditions in vitro. It also ameliorates cisplatin nephrotoxicity in vivo. We studied the effect of glycine on tubular necrosis from ischemia reflow and on inner stripe injury in an animal model of radiocontrast nephropathy. In all experiments, glycine (75 mg/100 g/h) increased tubular damage in the inner stripe. In the model of radiocontrast nephropathy, the percentage of medullary thick ascending limb (mTAL) necrosis at 24 hours increased from 22% +/- 6% to 41% +/- 9% or 55% +/- 7% with glycine infusion of 75 or 135 minutes, respectively (mean +/- SE, P less than 0.05, analysis of variance [ANOVA]). Renal function was not significantly affected. In rat kidneys subjected to ischemia reflow, mTAL injury following glycine increased from 1% +/- 0% to 12% +/- 6% (P less than 0.05) and from 8% +/- 5% to 49% +/- 8% (P less than 0.01) 24 hours after 30 minutes and 45 minutes ischemia, respectively. Tubular injury in the inner stripe was maximal in the deep interbundle zone, typical of hypoxic, rather than reperfusion, injury. Prior uninephrectomy increased inner stripe damage, but protected the proximal tubules. Both uninephrectomy and glycine infusion were found to contribute to mTAL necrosis. The infusion of glycine for 1 hour in intact rats increased renal blood flow by 44% and tripled urine volume (P less than 0.01). A parallel increase in glomerular filtration rate GFR; by 22% over 90 minutes) fell short of statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595708 TI - Renal malacoplakia with papillary necrosis and renal failure. AB - Renal parenchymal malacoplakia is a rare cause of renal failure. Patients presenting with renal failure carry a poor prognosis, the majority either dying or requiring chronic dialysis. In this report, we describe an alcoholic man who presented with renal failure due to bilateral renal parenchymal malacoplakia and papillary necrosis. The patient, who initially required dialysis, partially recovered renal function following prolonged antibiotic treatment with a fluoroquinolone antibiotic. PMID- 1595709 TI - Familial IgA nephropathy associated with bilateral sensorineural deafness. AB - Alport's syndrome is the most frequent disorder with familial nephritis and deafness, but other types of nephropathy have been occasionally associated with hereditary hearing loss. The familial occurrence of IgA nephropathy has been well documented. We report a family with hereditary, bilateral, sensorineural deafness spanning four generations. Three of five members with deafness had microscopic hematuria. Renal histology of the two deaf members undergoing biopsy showed mesangial glomerulonephritis with mesangial IgA deposits, without ultrastructural abnormalities of the glomerular basement membranes. Familial nephritis with deafness should not be equated with the diagnosis of Alport's syndrome. PMID- 1595710 TI - Peritonitis caused by Mycobacterium kansasii in a patient undergoing continuous ambulatory peritoneal dialysis. AB - Mycobacterium kansasii was isolated from the peritoneal fluid, peritoneal biopsy, and the Tenckhoff catheter of a 62-year-old woman undergoing continuous ambulatory peritoneal dialysis (CAPD) who presented with the clinical picture of peritonitis. To the best of our knowledge, this is the first case of CAPD associated peritonitis caused by M kansasii. Routine susceptibility tests using standard concentrations of isoniazid indicated isoniazid resistance; however, the organism was inhibited in vitro by a higher concentration of this drug. The patient responded to combination therapy with isoniazid and rifampin, as well as removal of the catheter. This report emphasizes the importance of mycobacterial cultures, in certain circumstances, in patients with CAPD-associated peritonitis and the utility of quantitative in vitro susceptibility testing. PMID- 1595711 TI - Posttransplant lymphoproliferative disorder presenting as an isolated skin lesion. AB - A case of posttransplant lymphoproliferative disorder (PTLD) presenting as an isolated skin lesion is reported. An initial superficial biopsy of the lesion was diagnosed as squamous cell carcinoma. After pathologic review of the biopsy and staining for immunoglobulins and Epstein-Barr virus (EBV) DNA, the correct diagnosis of PTLD was made. The patient had no systemic manifestations of lymphoma and the skin lesion was successfully treated with excision. Isolated skin lesions should be included among the potential sites for PTLD and histologic skin specimens from posttransplant immunosuppressed patients should be examined carefully for PTLD. PMID- 1595712 TI - Hypercalcemia, hypernatremia, and reversible renal insufficiency. PMID- 1595714 TI - The electrolytes in hyponatremia. PMID- 1595715 TI - Hospital pharmacies brace for release of antiendotoxin monoclonal antibodies. PMID- 1595713 TI - Can we regulate the quality of care?: the case of dialysis in Connecticut. PMID- 1595716 TI - Students' use of illicit drugs continues to drop, but rates in younger students surprise investigators. PMID- 1595717 TI - Incompatibility of injectable indomethacin with gentamicin sulfate or tobramycin sulfate. PMID- 1595718 TI - Visual compatibility of magnesium sulfate with narcotic analgesics. PMID- 1595719 TI - The culture and subcultures of pharmacy. PMID- 1595720 TI - Hospital pharmacy compliance with JCAHO standards and ASHP guidelines for reporting adverse drug reactions. AB - The extent to which institutional pharmacies comply with the accreditation standards of the Joint Commission on the Accreditation of Healthcare Organizations (JCAHO) and the ASHP guidelines for reporting adverse drug reactions (ADRs) was evaluated. A survey was mailed to directors of pharmacy at 444 randomly selected hospitals to collect information on their institutions' ADR programs; the survey addressed each point in the JCAHO accreditation standards and the ASHP guidelines. The 176 usable responses indicated that 89.8% of the institutions met all three of the JCAHO standards and 98.9% met at least two of them; 28.4% of the institutions complied with all 11 of the ASHP guidelines, and 89.2% complied with at least eight of them. Approximately 97% of the institutions had policies for ADR reporting. Respondents reported an average of 70.5 ADRs per hospital during 1989, of which 6.8 per hospital were reported to the FDA. More than 95% of all respondents indicated that they most frequently identified ADRs through voluntary reporting by health-care professionals. Respondents indicated methods and individuals responsible for reporting ADRs, notifying the physician and the FDA, and assessing severity and causality. Sixty-seven percent of the respondents indicated that they did not have a formal ADR committee for monitoring and evaluating ADRs. Almost 90% of the surveyed hospitals complied with all of the JCAHO standards for ADR reporting programs and at least 8 of the 11 ASHP guidelines for ADR monitoring and reporting. PMID- 1595721 TI - Use of an automated medication storage and distribution system. AB - The effects of an automated medication storage and distribution system in a hospital setting were evaluated. The Pyxis Medstation system was implemented on two nursing units at a 1000-bed tertiary-care referral hospital. The system, which is designed like an automated bank teller, dispenses items to authorized users and records all transactions. Floor-stock controlled substances and noncontrolled medications, large-volume i.v. solutions, and i.v. administration sets were stocked in the system. The system was evaluated (1) by comparing the mean patient charge capture rates for six months before and for three months after implementation, (2) by measuring nurse and pharmacy technician time required for various tasks before and after implementation, and (3) through questionnaires filled out by nurses and technicians. After the system was installed, nursing personnel spent less time on medication-related activities, charting, and documentation and more time interacting with patients. Pharmacy technicians spent more time on floor-stock activities and less time on billing activities. Nurses indicated positive attitudes toward the system features. Both nurses and pharmacy technicians indicated that the system should remain in use. After implementation, the charge capture rate for noncontrolled medications, i.v. solutions, and i.v. sets increased from 63% to 97%. This increase, extrapolated to the entire hospital, reflects $35,000 in additional revenue over the total costs of implementation of the system. Implementation of an automated medication storage and dispensing system is expected to increase hospital revenue and enable nurses to spend more time interacting with patients at this institution. PMID- 1595722 TI - Drug-food interaction counseling programs in teaching hospitals. AB - The results of a survey to characterize drug-food interaction counseling programs in teaching hospitals and solicit opinions on these programs from pharmacists and dietitians are reported. A questionnaire was mailed to the pharmacy director and the director of dietary services at teaching hospitals nationwide. The questionnaire contained 33 questions relating to hospital characteristics, drug food interaction counseling programs, and the standard calling for such programs issued by the Joint Commission on Accreditation of Healthcare Organizations. Of 792 questionnaires mailed, 425 were returned (response rate, 53.7). A majority of the pharmacists and dietitians (51.2%) did not consider their drug-food interaction counseling program to be formal; some had no program. The pharmacy department was involved more in program development than in the daily operation of such programs. The most frequent methods of identifying patients for counseling were using lists of patients' drugs and using physicians' orders. A mean of only five drugs were targeted per program. Slightly over half the respondents rated the Joint Commission standard less effective than other standards in its ability to improve patient care. A majority of teaching hospitals did not have formal drug-food interaction counseling programs. Pharmacists and dietitians did not view these programs as greatly beneficial and did not believe that the Joint Commission has clearly delineated the requirements for meeting its standard. PMID- 1595723 TI - Program for reviewing returned medications. AB - A program for reviewing medication doses returned to the pharmacy department is described. Discrepancies concerning returned doses at a teaching hospital led to the creation of a returned-dose log sheet. A pharmacist enters the patient's name, medication, and administration schedule and forwards a copy to the charge nurse on the patient's unit, who records the reasons for the return. A pharmacist then uses the form to resolve any discrepancies in the pharmacy records and follows up if necessary. Monthly summaries of the forms are prepared. After a pilot phase and educational feedback, the rate of return of log sheets by nurses increased to 95%. It took nurses about 10 minutes per unit to complete a form, and pharmacists required 15 to 20 minutes for completion and follow-up. The percentage of dispensed doses that were returned decreased from 1.1% during the first month of the full program to 0.4% during the eighth month. The most common reason given by nurses for returned doses was that the dose had already been charted as having been given. The therapeutic classifications most frequently represented by the returns were gastrointestinal drugs, cardiovascular drugs, anti-infective agents, and electrolytic, caloric, and water balance drugs. The use of a log sheet to document and explain the return of scheduled doses to the pharmacy department improved communication, resolved discrepancies in the records, and reduced the rate of returns. PMID- 1595724 TI - Pharmacist's obligation to hold confidential patient's intent to commit suicide. PMID- 1595725 TI - Perspective on sterile compounding practices and the draft guidelines. PMID- 1595726 TI - FDA issues import alert against unapproved mail-order drugs. PMID- 1595727 TI - Responding to media calls. PMID- 1595728 TI - A competency-based promotion program for part-time student employees. PMID- 1595729 TI - Controlling costs of new surgical products. PMID- 1595730 TI - Pharmacists should not accept gifts from industry. PMID- 1595731 TI - Establishing guidelines on pharmaceutical company support. PMID- 1595733 TI - Comments on the joint statement on the Pharm.D. degree. PMID- 1595732 TI - Comments on the joint statement on the Pharm. D. degree. PMID- 1595734 TI - Degree nomenclature. PMID- 1595735 TI - Degree nomenclature. PMID- 1595736 TI - Help the republics of the former Soviet Union. PMID- 1595737 TI - Pharmacy's position on health-care reform. PMID- 1595738 TI - Pharmacy's key to the kingdom. PMID- 1595739 TI - Drug information pharmacists at health-care facilities, universities, and pharmaceutical companies. AB - A national survey was conducted to provide a profile of drug information pharmacists. Questionnaires were mailed to 436 drug information pharmacists whose names were obtained from directors of drug information centers (DICs) at health care facilities, universities, and pharmaceutical companies. The net response rate was 64% (278 usable replies). Most respondents were 30 to 39 years of age and had practiced in drug information for four years or less. There were equal numbers of male and female respondents. More than half had a doctor of pharmacy (Pharm.D.) degree, and about half had completed a postgraduate residency or fellowship. Respondents with a Pharm.D. degree or postgraduate training reported a more favorable professional outcome, including position, income, and job satisfaction. Respondents reported a high level of professional involvement, including faculty appointment, publishing, and professional membership. Common reasons cited for choosing a career in drug information were an opportunity to continually learn, job satisfaction, and regular work hours. More than 70% of respondents were either very satisfied or extremely satisfied with their current job position. The most frequently reported income range was $40,000-44,999; distribution of income differed significantly among geographic regions. Drug information pharmacists report a high level of job satisfaction and involvement in professional activities; they often have completed advanced pharmacy education or postgraduate training. PMID- 1595740 TI - Evaluation of patient-care interventions by Pharm.D. clerkship students. AB - A program is described in which Pharm.D. clerkship students provide pharmaceutical care by identifying drug-related problems, suggesting interventions to solve the problems, and documenting the patient's outcome. Four doctor of pharmacy degree students under the direct guidance of a clinical pharmacy preceptor suggested 231 patient-care interventions during their clinical rotations; 219 (94.8%) of the interventions were either fully or partially accepted by the prescriber. The most commonly solved drug-related problems were underdose (31.5%) and overdose (17.4%), followed by untreated indications (14.1%) and drug given without indication (13.7%). The remainder of the drug-related problems that the students solved were improper drug selection, failure to receive drug, adverse drug reactions, or drug interactions. All but 10 interventions were considered by preceptors to be significant contributions to patient care. The interventions were estimated to have decreased drug costs in 50.7% of the cases, increased drug costs in 23.7% of the cases, and not changed drug costs in 25.6% of the cases. Patient outcomes were documented by the students in 58.9% of cases; the desired goals of the accepted intervention were achieved in all documented cases. A preceptor-supervised intervention program was beneficial to Pharm.D. students and patients and was well received by prescribers. PMID- 1595742 TI - Effect of using a standard polyvinyl chloride intravenous infusion set on patient response to nitroglycerin. PMID- 1595741 TI - Imipenem-cilastatin dosing intervention program by pharmacists. PMID- 1595743 TI - Stability of ifosfamide in 0.9% sodium chloride solution or water for injection in a portable i.v. pump cassette. PMID- 1595744 TI - Stability of ceftazidime and tobramycin sulfate in peritoneal dialysis solution. PMID- 1595745 TI - Hospital pharmacy in 1991: the year in review. AB - Issues and activities that dominated hospital pharmacy in 1991 are reviewed, and their relationship to political and economic trends of national and international importance is described. While rising costs, equitable reimbursement, and access to care continued to dominate the nation's health-care agenda in 1991, the growing interest in quality assurance was also noteworthy. Health-care reform will likely be a dominant issue during the current election year, and pharmacists are urged to play an active role in this restructuring process, both within their work settings and in their communities. Among the major concerns of hospital pharmacy in 1991 were the appropriate use of the new products of biotechnology, advances in computer and communications technology, and measuring and improving the quality of pharmaceutical care. Other issues highlighted in the literature included the need to articulate a mission statement concerning pharmaceutical care, the role of specialization in pharmacy practice, and the appropriate allocation of human resources. The literature of hospital pharmacy continues to provide insight into the progress of the profession and to serve as a benchmark that will gauge its future course. PMID- 1595746 TI - Experiences of a combat support hospital pharmacy service during Operation Desert Storm. PMID- 1595747 TI - Practical guidelines for preparing and administering amphotericin B. AB - Current practices used in the preparation and administration of amphotericin B are evaluated, and updated guidelines are presented. Intravenous admixtures of amphotericin B 0.25 and 1.4 mg/mL in 5% dextrose injection have an expiration date of 35 days and 36 hours, respectively. Since commercial formulations of amphotericin B lack a bacteriostatic agent, admixtures should be stored at 4-8 degrees C. Protection from fluorescent light is unnecessary. Admixtures may be prepared in polyolefin, glass, or polyvinyl chloride intravenous containers; certain evacuated intravenous containers contain buffers that can cause precipitation of amphotericin B. The addition of a buffering agent to the intravenous admixture is unnecessary when the initial pH of the 5% dextrose injection exceeds 4.2. The usual daily maintenance dose of amphotericin B is 0.5 1 mg/kg i.v. The manufacturer recommends beginning intravenous therapy with a 1 mg test dose. The initiation of therapy with incrementally increased doses may be detrimental if it delays the delivery of a therapeutic dose. Amphotericin B can be infused over one to two hours (less than or equal to 50 mg/hr) in patients with adequate renal function. Bladder instillation of amphotericin B 50 mg in 1 L of sterile water has been used to treat fungal cystitis. Ancillary medications administered to treat infusion-related adverse events should be used as prophylaxis in patients with a history of hypersensitivity or unacceptable reactions and as needed for relief of symptoms. Sodium supplementation should be implemented cautiously, on a patient-specific basis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595748 TI - Prevention of Lyme disease. AB - Lyme disease and the use of tick repellents and physical protective measures to prevent the disease are discussed. Lyme disease is a multiple-organ-system, immune-mediated inflammatory disorder transmitted by the bites of ixodid ticks infected with Borrelia burgdorferi. An individual is at greatest risk for infection when a tick has been attached to the skin for more than 24 hours. Lyme disease occurs in three stages and may affect the skin, nervous system, cardiac system, and joints. Antimicrobials used in management consist primarily of penicillins, cephalosporins, tetracyclines, and erythromycin. Tick repellents are divided into those applied to the skin and those applied to clothing. Skin repellents include N,N-diethyl-meta-toluamide (DEET), 2-ethyl-1,3-hexanediol, and dimethyl phthalate. Permethrin is by far the most effective clothing repellent. DEET plus a permethrin-containing clothing repellent offers the best overall protection. The adverse effects of repellents are minimal, but cases of hypersensitivity have been reported, especially in children. Physical measures to prevent tick bites include avoiding tick-infested areas, wearing light-colored clothing for easy identification of crawling ticks, regularly checking the body and pets for ticks, wearing protective garments and closed-toed shoes, and removing attached ticks promptly by using tweezers or forceps to apply a steady upward pull. A vaccine for the active immunization of humans against Lyme disease remains to be developed. Although antimicrobial therapy is available for persons with Lyme disease, the best approach for those who may be exposed to infected ticks is to apply topical skin or clothing repellents and to practice common sense measures of physical protection. PMID- 1595749 TI - Hospital liable for defect in cardioplegia solution. PMID- 1595750 TI - Battered bottom lines: the impact of eroding pharmaceutical discounts on health care institutions. AB - For several years, the American Society of Hospital Pharmacists (ASHP) has voiced concern about the impact of federally mandated changes on the pharmaceutical products marketplace. Since this marketplace is relatively inelastic, manipulating one segment in the interest of cost efficiencies is likely to result in price increases in other segments. That manipulation could come through such decisions as a "one-price" policy for pharmaceuticals, mandatory rebates for certain segments of the marketplace, or the elimination of discounts. The issue of cost-effective purchasing of prescription drugs and related supplies has recently come under increased scrutiny from the U.S. Congress, the Department of Health and Human Services, the General Accounting Office, and the Federal Trade Commission. In light of these and future activities, ASHP determined that there was a need to collect credible data on the potential impact of the termination of the Robinson-Patman Act's nonprofit institutional exemption, other discounts, or both on pharmaceutical expenditures in institutional health-care settings. The authors of this paper report the results and analysis of a 1990 mail survey conducted by ASHP and Concepts in Healthcare, Inc., to collect information on pharmaceutical purchasing and discounting procedures in community hospitals and selected nonhospital settings in the United States. Survey respondents reported that they would expect substantial increases in pharmaceutical expenditures if volume and nonprofit discounts were eliminated. Nonprofit hospitals expected a 24.4% increase in pharmaceutical expenditures in the wake of discount elimination, while for-profit institutions projected an 11.9% increase. Pharmaceutical expenditures of the study hospitals averaged $1.69 million per year; respondents estimated that this sum would increase by $390,000 (23.1%) if volume and nonprofit discounts were eliminated. PMID- 1595751 TI - Reassessing the membership structure of ASHP. AB - In this discussion paper, the ASHP Board of Directors suggests that it is time for the American Society of Hospital Pharmacists to move to another stage in the development of its membership structure. In 1975, ASHP broadened its purview to represent pharmacists who practice in all types of organized health-care settings. The Board has observed that ASHP members today often identify more strongly with their specific practice type or specialty than with "hospital pharmacy" or "pharmacy practice in organized health-care settings." Further, such members prefer to engage in organizational activities with peers from their specific area of practice. This has led the Board to examine the membership structure of the Society in an effort to improve ASHP's effectiveness in exercising leadership for pharmacy practice in organized health-care settings. The Board suggests for consideration by ASHP members two types of changes in membership structure: (1) the creation of sections and (2) the establishment of affiliation arrangements with national organizations that share ASHP's orientation toward pharmacy practice in organized health-care settings. The Board recognizes that membership sections would have to be given substantial autonomy for them to be effective. The Board believes that a pilot or experimental approach should be used in making changes in membership structure, with explicit evaluation after a period of time. The Specialty Practice Group and Practice Management Group programs are also being reassessed by the Board. Finally, the full name of ASHP will be reconsidered. PMID- 1595753 TI - Report on recent ASHP student activities. PMID- 1595752 TI - A new headquarters building for ASHP. PMID- 1595754 TI - Psychopharmacologic approaches to therapy for chest pain of presumed esophageal origin. AB - Psychoactive medications have been used to manage chest pain of presumed esophageal origin, especially in syndromes associated with esophageal motor dysfunction. The rationale for their use is based on (a) the high prevalence of psychiatric disorders reported in patient groups with esophageal symptoms and minor motor dysfunction, (b) recognized psychophysiologic effects on esophageal motor activity, (c) the potential benefits that nerve-modulating drugs may have on the pathogenesis of the syndromes (independent of psychiatric factors), and (d) observations from treatment trials for chronic pain--including irritable bowel syndrome, a disorder that shares some clinical features with functional esophageal chest pain. Although psychiatric factors may have interactive effects on the presentation and course of reflux disease, the use of psychoactive drugs in reflux disease has not been tested. The effects of psychoactive drugs have been systematically explored and documented in only one study. At present, the mechanisms of esophageal symptom reduction resulting from psychopharmacologic treatments are not clear, but reduced sensitivity to visceral stimuli remains one possibility. PMID- 1595755 TI - Mechanisms of esophageal pain. AB - Esophageal pain is transmitted via the sympathetic nervous system to the spinal cord, in which pain from visceral and somatic sources ascends to higher centers in the brain. Primary afferent neurons are bipolar, with the peripheral end specialized to be a sensory receptor. Nociceptors of somatosensory afferents are free nerve endings that can be activated by mechanical, thermal, or chemical stimuli. Esophageal nociceptive neurons have not been specifically identified but probably are also free nerve endings. Most esophageal spinal mechanoreceptors have been shown to be nociceptive. Some esophageal mechanonociceptors have a wide dynamic range and respond to physiologic and painful stimuli, while others have a high threshold of stimulation and are solely nociceptive. Esophageal spinal afferents have their cell bodies in the dorsal root ganglia and contain substance P and calcitonin gene-related peptide. These putative neurotransmitters are transported in both the peripheral and central directions of bipolar afferent neurons. Primary afferent neurons are likely to also contain an excitatory amino acid neurotransmitter such as glutamate. Centrally, nociceptive primary afferents terminate on neurons in specific layers of the dorsal horn of the spinal cord. Convergence of multiple visceral afferents with somatic afferents onto the same dorsal horn neurons may explain referred pain. A patient's inability to distinguish esophageal from cardiac pain may be due to convergence of pain pathways. Second-order neurons in the dorsal horn project in the anterolateral system to the brain. Within the anterolateral system, nociception ascends in the spinothalamic, spinoreticular, and spinomesencephalic tracts. The thalamus relays fast pain to the postcentral areas of the parietal lobe of the cortex. Pathways to the reticular formation are slow and may mediate the increased arousal that occurs in response to pain. The spinomesencephalic tract projects to midbrain sites including the periaqueductal gray. Organ-specific pathways in the brain have yet to be defined, but neuroanatomic tracing techniques employing neurotropic viruses are being developed. The perception of pain can be influenced at multiple levels, such as the receptor in the esophagus, the synapses in the dorsal horn of the spinal cord or thalamus, or the cortex. A fundamental mechanism of modulating nociception is descending inhibition.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1595756 TI - Psychological treatment of noncardiac chest pain: the cognitive approach. AB - Chest pain often accompanies panic attacks. The success of cognitive therapy in the treatment of panic disorder has led to effective cognitive--behavioral therapy for both anxiety about health and noncardiac chest pain accompanied by anxiety. The cognitive hypothesis proposes that, in vulnerable persons, sensations in the chest region can be misinterpreted as a sign of serious illness, such as an impending heart attack, giving rise to anxiety. A variety of responses can contribute to the problem of such misinterpretations and the associated anxiety. First, anxiety-induced autonomic arousal can generate an increase in symptoms. Second, worried patients are more likely to focus on their bodily reactions and to check their bodily functioning, increasing the likelihood that some changes will be detected. Third, patients may seek medical evaluation or other forms of reassurance, which can lead to further misinterpretation and worry. Each of these reactions can increase the perception of chest pain, contributing to a vicious cycle that exacerbates both the chest pain and the anxiety. In most cases, treatment is straightforward. It starts with identification of the patient's particular fears, followed by education about the role of anxiety in producing physical sensations such as chest pain. Demonstration of the processes that produce and maintain physical sensations usually convinces the patient of the harmless nature of symptoms. Although cognitive therapy avoids giving reassurance by "ruling out" feared diseases, patients are encouraged to take actions to disconfirm their worst fears. Some patients require more specialized treatment, particularly if they remain strongly convinced that their problem is solely physical. Such patients must be engaged in active collaboration with the therapist. PMID- 1595757 TI - Therapy of noncardiac chest pain: is there a role for surgery? AB - Esophageal distention, motor abnormalities, or exposure of the esophageal mucosa to acidic gastric juice can cause chest pain indistinguishable from that of myocardial ischemia in patients with and without coronary artery disease. In these situations the exact cause of the symptom needs to be established prior to any surgical therapy. An antireflux procedure relieves chest pain in patients with increased esophageal acid exposure more reliably than medical therapy. The best results are obtained in patients in whom a direct correlation of the symptom with reflux episodes can be documented on 24-hour esophageal pH monitoring. Ambulatory 24-hour esophageal motility monitoring shows that esophageal motor disorders are a less frequent cause of noncardiac chest pain than suggested by standard manometry or provocation tests. Furthermore, chest pain episodes in patients with esophageal motor abnormalities are not associated with single contractions of excessively high amplitude or duration. Rather, the symptom appears to be triggered by an increased frequency of simultaneous, multipeaked, and repetitive motor activity. In appropriately selected patients with chest pain and dysphagia secondary to an esophageal motor abnormality, a long esophageal myotomy eliminates the ability of the esophagus to produce these contractions, reduces or eliminates dysphagia, and decreases the frequency and severity of chest pain episodes. PMID- 1595758 TI - Esophagomyotomy for noncardiac chest pain resulting from diffuse esophageal spasm and related disorders. AB - Esophagomyotomy was performed in 42 patients with chest pain resulting from diffuse esophageal spasm and related disorders. The procedure used restricted the myotomy to the diseased portion of the esophagus, as demonstrated manometrically. More than half of the patients also required myotomy of the lower esophageal sphincter. Some patients required other surgical procedures. Overall results were excellent; the overall improvement rate was 70% at a median follow up of 5 years, 8 months. Postoperatively, 5 patients had recurrent or persistent pain. Esophagomyotomy is recommended for selected patients with clinically significant chest pain and/or dysphagia. PMID- 1595759 TI - Chest pain of undetermined origin: overview of pathophysiology. AB - Patients with unexplained chest pain represent a major clinical dilemma for primary-care physicians, gastroenterologists, and cardiologists. References to this prevalent clinical problem date to more than 150 years ago; confusion about its pathophysiology has resulted in the use of a variety of descriptive terms such as "noncardiac," "atypical," and "angiographically negative" chest pain. Since none of these terms applies to all cases, the description "chest pain of undetermined origin" may be preferable. Because the esophagus has a similar location and innervation as the heart, an esophageal source for unexplained chest pain syndromes has been frequently suggested. Recent studies have emphasized the importance of gastroesophageal reflux as a likely component of esophageal pain. Moreover, "irritable esophagus" is an emerging concept that implies a generalized alteration in esophageal pain threshold, that is, abnormal nociception. The potential effects of stress or altered psychological states in this phenomenon must be considered, and the role of "panic attacks" in the production of pain in these patients needs to be clarified. In addition, stress may produce altered esophageal motility and lead to manometric abnormalities such as the "nutcracker esophagus" or a hypertensive lower esophageal sphincter. Finally, the precise contribution of the heart in producing pain in patients with normal coronary angiograms remains unclear because the precise role of microvascular angina has yet to be clarified. PMID- 1595760 TI - Esophageal balloon distention and cerebral evoked potential recording in the evaluation of unexplained chest pain. AB - A minority of patients presenting with the common clinical challenge of unexplained chest pain can be diagnosed as having an esophageal etiology for their pain using conventional manometric and provocative (acid infusion and edrophonium) testing. Esophageal balloon distention may provide an important adjuvant to routine testing. Most pain from the esophagus is mediated by visceral sensory receptors located near the myenteric plexus; these receptors respond to movements of the organ wall in response to contractions or distention. Balloon distention can be used to simulate this wall movement. Early clinical studies have been expanded by recent investigations demonstrating a lowered pain threshold in response to balloon distention in patients with both unexplained chest pain and nonobstructive dysphagia. The physiologic basis for this increased sensitivity is not clear. Balloon distention has several effects on esophageal motility that may play a role in producing pain. The recording of cerebral evoked potentials is a technique newly developed to provide an objective measurement of the subjective sensation of pain. Electrical and mechanical stimulation of the esophagus has been shown to produce cerebral evoked potentials. Recent investigations of cerebral potentials evoked by balloon-induced esophageal stimulation have confirmed that this response depends on pain production, have clarified the appropriate stimulus parameters, and have localized the site of origin of the evoked potential to the balloon site. Balloon distention may prove to be an important addition to current esophageal provocative testing, although widespread applicability has been hampered by the lack of a commercially available standardized balloon. Recording evoked potentials produced by esophageal stimulation may provide additional clues in unraveling the mystery of unexplained chest pain. PMID- 1595761 TI - Irritable esophagus. AB - An esophageal origin of noncardiac chest pain is generally accepted if prolonged pH and pressure recordings show that the pain episodes correlate in time with acid reflux, esophageal motor abnormalities, or a combination of both, or if provocative testing (acid perfusion, edrophonium, balloon distention) is positive. Many patients with noncardiac chest pain of esophageal origin are said to have an irritable esophagus. Irritable esophagus has been defined in two ways. Some researchers suggest it is actually a lowered esophageal pain threshold, based on the finding that such patients feel chest pain at lower balloon volumes than controls during intraesophageal balloon distention; they are said to be hypersensitive to balloon distention. Hypersensitivity to an esophageal stimulus is generally found in patients with noncardiac chest pain of esophageal origin, and hypersensitivity to a single stimulus is one criterion for a diagnosis. Our group defines irritable esophagus as a condition in which several different stimuli result in the same type of chest pain. Accordingly, we have grouped patients with esophageal chest pain into three categories: (a) patients with an acid-sensitive esophagus, in whom spontaneous pain episodes can be related to acid reflux (with or without accompanying motor disorders), and/or the acid perfusion test is positive; (b) patients with a mechano-sensitive esophagus, in whom the spontaneous pain episodes can be related to motility disturbances (without reflux), and/or the edrophonium test or balloon distention test is positive; (c) patients with an irritable esophagus, in whom some spontaneous pain episodes are related to reflux, while others are related to abnormal motility (without reflux). The last group includes patients whose spontaneous chest pain is related to reflux, with a positive motility tests; whose pain is related to abnormal motility, with a positive reflux test; and patients with positive tests for both reflux and abnormal motility. Seven studies examined a total of 281 noncardiac chest pain patients using prolonged pH and pressure recordings and provocative tests. An acid-sensitive, a mechano-sensitive, or an irritable esophagus was found in 20%, 14%, and 24% of patients, respectively. PMID- 1595762 TI - Panic disorder in patients with angiographically normal coronary arteries. AB - Several lines of investigation strongly support the notion that panic disorder afflicts at least one third of patients with angiographically normal coronary arteries and unexplained chest pain. Panic disorder is a common problem, affecting 1-2% of the U.S. population. Current research suggests an etiology that is both psychophysiologic and cognitive. The locus ceruleus and cortico-releasing factor are implicated in the biological circuit associated with panic attacks, while psychological research indicates that catastrophic thinking, phobic responses to somatic sensations, and repressed anger, grief, and traumatic events play a part in triggering attacks. Treatment consists of pharmacologic interventions, including antidepressants and benzodiazepines, as well as psychotherapeutic work focusing on catastrophic thinking and repressed anger, grief responses, and other traumatic experiences. PMID- 1595763 TI - Overview of diagnostic testing for chest pain of unknown origin. AB - Identifying the cause of recurrent chest pain may be difficult. Significant coronary artery disease must be excluded before patients can be assured that their symptoms are truly "noncardiac." A normal coronary angiogram is the most definitive test but this may not preclude the presence of a new "fly in the ointment," i.e., microvascular angina. Musculoskeletal pain syndromes, psychological problems, and esophageal disorders, including both esophageal motility disorders and gastroesophageal reflux disease, are the most common causes of noncardiac chest pain. Nearly 30% of these patients will have an esophageal motility disorder, although its clinical relevance in the asymptomatic patient is controversial. Simple, inexpensive, provocation tests (most commonly edrophonium, bethanechol, and/or balloon distention) have been developed to recreate motility-related chest pain in the laboratory. These tests can identify the esophagus as the source of pain, but in most cases they do not direct therapy. Other disadvantages of provocation tests include the lack of a gold standard reference point, side effects, and the need for placebo because of a subjective end point. Recently, ambulatory esophageal pH and pressure monitoring have been used to define precisely the cause of esophageal chest pain. These systems can record multiple episodes of pain for up to 24 hours in an outpatient setting and have shown that gastroesophageal reflux (rather than motility disorders) is the most common esophageal cause of pain. However, these studies also suggest that many episodes of chest pain do not have an identifiable esophageal cause. Furthermore, this equipment is expensive, uncomfortable, may alter normal activity, and is not useful in patients having infrequent pain episodes. Psychological disturbances should be carefully sought in any patient with noncardiac chest pain: Many patients have anxiety, depression, or panic attacks that may complicate or contribute to their reported symptoms. It is questionable if these patients need additional testing. Rather, the challenge of the future is to prove that the multitude of tests aid in the overall treatment and outcome of patients with noncardiac chest pain. PMID- 1595764 TI - Excluding heart disease in the patient with chest pain. AB - Angina pectoris is chest discomfort associated with myocardial ischemia. When coronary blood flow is inadequate to meet myocardial tissue demand, lactate accumulates, resulting in diastolic and systolic left ventricular dysfunction. This leads to ST-segment abnormalities and eventually to angina pectoris. Angina, most commonly a pressure-type sensation in the midanterior chest precipitated by exercise, stress, or cold, typically lasts 1-5 minutes and is alleviated by rest or nitroglycerin. Diagnostic studies to assess myocardial ischemia include treadmill exercise testing, Holter monitoring, and coronary angiography. Treadmill exercise testing has a relatively low accuracy for diagnosing coronary artery disease. This can be improved by combining exercise with thallium-201 imaging, two-dimensional echocardiography, or positron emission tomography (PET). Thallium-201 scintigraphy and exercise echocardiography have reported sensitivities of 70-85% and specificities of 50-60% when applied to low-risk, asymptomatic populations. PET scanning has a high predictive accuracy (sensitivity 90%, specificity 90-95%) and is more useful as a screening test; it can also assess the functional significance of coronary artery stenoses and differentiate viable myocardium from infarcted tissue. Holter monitoring is too insensitive and nonspecific to be used as a screening test for coronary artery disease; it can, however, assess the total ischemic burden in patients with known coronary artery disease and correlate symptoms and ST-segment abnormalities during episodes of pain at rest. Coronary angiography has been the gold standard for diagnosing coronary artery stenoses. Quantitative angiography has improved the assessment of coronary artery narrowing but is still limited in evaluating coronary blood flow. Doppler flow studies provide useful information regarding coronary flow reserve. Myocardial ischemia as a cause of chest pain is determined by evaluating the clinical characteristics consistent with angina, correlating electrocardiographic abnormalities with perfusion defects or wall motion abnormalities, and determining the extent and functional significance of coronary artery stenoses by coronary angiography. PMID- 1595766 TI - Microvascular angina and the sensitive heart: historical perspective. AB - As our understanding of the etiology of chest pain of undetermined origin has evolved, the focus for studying this problem has switched from individual subspecialties to a multidisciplinary approach. In the subspecialties of gastroenterology and cardiology, the focus has shifted from organ-specific diagnoses to concepts of altered pain thresholds. Cardiologists began to look for functional causes of ischemia following the recognition that many patients with chest pain had normal coronary arteries. Abnormal responses of the coronary microcirculation to stress were identified in this population, and the concept of "microvascular angina" originated. Further evaluation, however, demonstrated that many of these patients did not have evidence of ischemia. In addition, a significant overlap with esophageal motility disorders was shown, and multiple sensitivities to otherwise nonirritating stimuli, whether in the heart or the esophagus, could be elicited in these patients. This finding led to the concept of abnormal visceral nociception, that is, the "sensitive heart" and the "tender esophagus," both the focus of ongoing clinical research. PMID- 1595765 TI - Anginal pain of esophageal origin: clinical presentation, prevalence, and prognosis. AB - Since 1768, when Heberden recognized a relationship of angina pectoris with eating, the close resemblance between angina-like pain of esophageal and cardiac origin has led to diagnostic confusion, with the role of the esophagus being, in turn, over- and underemphasized as a cause of symptoms. Although the classic features of angina do not distinguish the origin of the pain, certain other symptoms may identify esophageal pain. These include an inconsistent correlation of exercise with pain, periods of prolonged remission, provocation of pain by posture, association with other esophageal symptoms, relief by antacids, radiation of pain down the right arm and into the back, occurrence of pain at night, continuation of pain as a background ache, and relief from nitroglycerine delayed by 10 minutes or longer. However, while certain symptoms may alert the clinician to the possibility that angina-like pain is due to esophageal disease, no single symptom or combination of symptoms is infallible; there is no alternative to careful assessment. Esophageal disease accounts for the greatest number of patients with chest pain of unknown origin. The prevalence of angina like esophageal pain in unselected emergency admissions with suspected myocardial infarction is 10-20%. Approximately one third or more of patients with angina and normal coronary arteries have esophageal problems. We have followed patients with angina-like esophageal pain for 9 years. Although prognosis remains good, confirming the original noncardiac diagnosis, greater than 80% of patients continue to have chest pain of undiminished intensity, and half are limited in their ability to work. Reassurance appeared to have one beneficial result: Patients were less likely to consult a physician after a positive diagnosis had been made. PMID- 1595767 TI - Provocation testing in noncardiac chest pain. AB - The ability to reproduce chest pain and to identify the esophagus as the source of this pain are the major reasons why provocation testing has become standard in the evaluation of patients with noncardiac chest pain. Recent studies that challenge the validity of performing provocation tests have polarized experts into two camps: those who would abandon such testing because of its low sensitivity and low specificity, and those who would use testing judiciously because of moderate increases in diagnostic yield. Use of 24-hour pH and pressure testing has shown a high number of chest pain events associated with acid reflux in patients with positive cholinergic stimulation tests and esophageal dysmotility, as well as pain with esophageal dysmotility in patients with positive acid infusion tests. Mechanisms of esophageal chest pain are not known. All provocation agents can decrease coronary flow reserve (i.e., induce microvascular angina), thus raising the question of a cardiac source of pain even in patients with positive presumed esophageal provocation. Acid infusion, cholinergic stimulation, and balloon distention are discussed in light of 24-hour pH and pressure monitoring. Esophageal distention and the role of acid in inducing chest pain are emphasized. The role of stress, the use of defined stressors to induce chest pain, and altered pain perception as a final common pathway for chest pain are examined. PMID- 1595769 TI - Ambulatory esophageal monitoring in noncardiac chest pain. AB - The esophageal origin of angina-like noncardiac chest pain can be identified with certainty only when spontaneous chest pain episodes are associated with gastroesophageal reflux, abnormal esophageal motility, or both. Since noncardiac chest pain typically occurs infrequently, prolonged monitoring is required to establish such an association. Ambulatory esophageal monitoring offers the additional advantages of studying the patient in everyday life and avoiding hospital admission. Although the amplification and storage of 24-hour signals in a portable recorder no longer poses technical problems, the complexity of the analysis of the recorded signals should not be underestimated. For noncardiac chest pain, the most relevant part of the analysis is the association between chest pain episodes and the recorded esophageal signals. To determine whether contraction amplitude or duration during chest pain episodes is abnormal, their measurements are compared with baseline values from the same patient. Fully automated analysis by computer is feasible and, since it avoids observer bias, preferable. The yield of 24-hour monitoring in noncardiac chest pain reported by different groups of investigators varies considerably. Motor abnormalities have been identified as the cause of chest pain in 4.5-18% of patients studied, and reflux in 4.5-25%. In addition, some patients had both dysmotility- and reflux related pain episodes. As expected, the yield of the technique is higher in patients with frequent pain episodes. In patients who do not experience pain during 24-hour monitoring, the technique cannot provide a firm diagnosis of pain of esophageal origin. Recently, a much higher yield of 24-hour monitoring was reported in patients with noncardiac chest pain admitted to a coronary-care unit. A total of 76% of these patients were found to have either reflux- or dysmotility related chest pain. Despite its relatively low yield, the addition of esophageal pressure monitoring to ambulatory pH monitoring is worthwhile and probably also cost-effective in patients with frequent episodes of unexplained chest pain. PMID- 1595768 TI - Psychosocial and psychophysical assessments of patients with unexplained chest pain. AB - It is imperative to assess the psychosocial factors that may influence the subjective experiences and pain behavior of persons with chronic unexplained chest pain. Both psychologists and physicians tend to rely on self-report measures of psychological distress, which provide little unique information about patients with chronic chest pain to differentiate them from patients with other painful disorders such as irritable bowel syndrome, gastroesophageal reflux disease, or coronary artery disease. However, assessment of pain-coping strategies, spouse responses to the patient's pain behaviors, and pain thresholds for esophageal balloon distention do differentiate patients with chronic chest pain from healthy controls and patients with various other chronic pain disorders. Specifically, chronic chest pain patients tend to use relatively passive pain-coping strategies such as praying and hoping, and to report relatively high levels of spouse reinforcement of pain behaviors. Finally, in response to esophageal balloon distention, chronic chest pain patients display low pain thresholds that do not generalize to stimulation by mechanical finger pressure. Preliminary evidence suggests these low thresholds are due primarily to a tendency to set low standards for making pain judgments regarding esophageal stimuli of moderate-to-high intensity levels. PMID- 1595770 TI - Critique of the session on diagnostic testing. AB - During the session on diagnostic testing, various diagnostic tests used to identify the cause of chest pain were discussed. This critique of diagnostic assessments of the complex etiology of chest pain is presented as a contribution toward further investigation and clarification of this difficult clinical syndrome. The first step in the evaluation process is to exclude coronary artery disease. Patients with angina and normal coronary artery flow may have atypical disease, such as microvascular angina or syndrome X. The precise relationship between these disorders and esophageal disease or gastroesophageal reflux, as well as their possible involvement in chest pain of undetermined origin, requires further definition. A limitation of esophageal provocation tests is that they may identify the esophagus as the source of pain without determining the specific esophageal disorder that causes the pain. Problems associated with 24-hour pH and pressure monitoring include (a) poor correlation between reflux episodes and heartburn symptoms, (b) the lack of a good functioning swallowing signal, and (c) the huge amount of data that must be analyzed, along with shortcomings in computer-aided analysis. Nevertheless, the various available diagnostic tests can provide important information to the clinician. PMID- 1595771 TI - Issues in the treatment of noncardiac chest pain. AB - Evaluation of therapy for noncardiac chest pain calls for a systematic analysis of all relevant factors. Central chest pain is often experienced as a threat to life. Fear and anxiety concerning heart disease or cancer can increase pain and hamper therapy. The relief of pain can result from factors other than the actual treatment employed (i.e., placebo effects, relief of anxiety, spontaneous improvement, changes in life-style not related to treatment, or other, concomitant therapies prescribed). Therapeutic failure may be explained by diagnostic error, incorrect treatment, insufficient duration of therapy, incorrect dosage regimen, individual response to pharmacologic agents, poor drug absorption, drug interactions, poor compliance, poor surgical technique, and, finally, lack of effective therapeutic options. The rational evaluation of therapy for noncardiac chest pain is also hampered by its multifactorial etiology and the difficulty of selecting study patients with identical pain etiology. Controversies in the treatment of noncardiac chest pain reflect the uncertainty regarding pathophysiology. A primary issue is whether to treat patients medically with life-style modifications and pharmacologic agents, or surgically. A variety of pharmacologic agents and surgical techniques have been used to treat noncardiac chest pain. Treatment includes psychosocial considerations in addition to medical or surgical therapy. The most important role for the physician of a patient with noncardiac chest pain is to listen well, to be confirming and understanding, and to treat the patient not just as an apparatus that needs repair but as a socially integrated human being. PMID- 1595773 TI - Current medical therapy for esophageal motility disorders. AB - Treatment of patients with an esophageal source of chest pain remains a challenging problem. Although a variety of measures--including nitrates, anticholinergics, sedatives, calcium channel antagonists, esophageal dilation, and psychological reassurance--are available for the management of esophageal chest pain, none has emerged as the treatment of choice. Studies of nitrate preparations for the treatment of painful motility disorders are limited by a small number of patients and the lack of randomized, placebo-controlled investigations. The efficacy of anticholinergic drugs in hypercontractile esophageal motility disorders has not been reported. In the only prospective placebo-controlled trial using an anti-depressant, trazodone was superior to placebo in relieving symptoms in patients with a variety of esophageal motility disorders. Conflicting results have been described in placebo-controlled trials of the calcium channel antagonists nifedipine and diltiazem in patients with "nutcracker esophagus" or diffuse spasm. Information about the efficacy of verapamil and hydralazine is limited. Esophageal dilation has been useful in selected patients. For many patients, esophageal chest pain may be associated with gastroesophageal reflux. Treatment of these patients with nitrates, calcium channel antagonists, or anticholinergics may aggravate their reflux. The mechanisms of esophageal chest pain remain unknown. Recent studies have suggested that abnormal motility may not be the only factor associated with chest pain. An important number of patients have behavioral abnormalities, increased nociception, impaired coronary vasodilatory reserve, or a diffuse abnormality of smooth muscle. Research into rational therapy for chest pain patients should take into account the contribution of these other factors. PMID- 1595772 TI - Medical therapy for gastroesophageal reflux disease. AB - Gastroesophageal reflux disease (GERD) remains a ubiquitous problem, although therapeutic options continue to evolve. Effective therapy calls for understanding the pathogenesis. Key factors associated with GERD include incompetence of the lower esophageal sphincter, esophageal clearance, gastric contents, tissue resistance, and potency of the refluxate. Phase-type directed therapy remains the best treatment approach and histamine (H2)-receptor antagonists are now the cornerstone of therapy for patients not responsive to conservative measures. In a subset of patients with severe esophagitis who do not respond to conventional H2 receptor antagonist therapy, efficacy has been demonstrated with high-dose therapy. The acid suppressant omeprazole, highly effective in erosive esophagitis, is the drug of choice for esophagitis resistant to H2-receptor antagonists. Despite effective forms of therapy, relapse rates are high in patients with severe GERD, and maintenance therapy typically is required. With near uniformity, efficacy end points for these agents have been directed toward relief of heartburn, regurgitation, and dyspepsia. Few data exist correlating relief of GERD and improvement of chest pain. Although therapeutic strategies for treating GERD have improved, empiric treatment of suspected GERD in the patient with noncardiac chest pain does not appear to be the optimal approach and should be reserved for cases where diagnostic testing is limited or unavailable. PMID- 1595774 TI - Potential precipitating factors of the onset of myocardial infarction. AB - Myocardial infarction (MI) usually results from thrombotic coronary artery occlusion at the site of a ruptured atherosclerotic plaque. The factors responsible for triggering MI are not known but conditions that increase serum catecholamines may be involved. Accordingly, the authors prospectively evaluated the presence of factors that may increase catecholamines immediately prior to MI in 186 patients. Myocardial infarction was documented by a rise in serum CK-MB. There were 149 men and 37 women, aged 57 +/- 12 (mean +/- SD) years. All patients were interviewed within 72 hours of admission concerning strenuous physical activity, emotional stress, and assumption of the upright posture immediately prior to the onset of symptoms. Seventy-five (40%) patients had one or more of these factors immediately prior to the onset of MI chest pain. Fourteen (8%) experienced acute emotional upset; 28 (15%) were involved in strenuous physical activity; and 39 (21%) had suddenly changed position. In the latter group, 18 changed from being supine for more than 1 hour to standing; three rose from supine to sitting; and 18 changed from prolonged sitting (greater than 60 minutes) to standing. The conclusion is that a potential triggering factor is present in many patients immediately prior to the onset of MI. A sudden change in position is the most frequent potential trigger, typically occurring the morning after awakening from sleep. PMID- 1595775 TI - Charting of daily weight pattern reinforces maintenance of weight reduction in moderately obese patients. AB - To maintain reduced body weight by behavioral therapy in moderately obese patients, body weight was measured four times daily and charted in a weekly graph. Seventy-two female patients with simple obesity were divided into two groups: 55 patients with appliance of charting of weight pattern (group-I), and 17 patients without the charting (group-II). The percentage of patients followed for 2 years was different between group-I (87%) and group-II (65%) during 2 years after completion of weight reduction therapy interviews (p less than 0.05). Forty eight of group-I patients succeeded in decreasing their weight by 15.2 +/- 1.5 (mean +/- SEM) kg during the 6.5 +/- 0.8 months of the therapy interviews. They were followed up for 3.8 years with no rebound weight gain. Eleven patients in group-II also succeeded in decreasing their weight by 16.8 +/- 1.9 kg during 7.8 +/- 1.3 months but their body weight rebounded by 9.0 kg during the 2-year followup period. Twelve of 15 male patients with weight charting maintained reduced weight during 4.3 years. It was easier and more effective for obese patients to maintain weight graphs for the longer period than to record no weight graphs. Obese patients could themselves monitor irregular weight patterns produced by overeating and correct the irregularities in food intake and daily lifestyles. This seems to explain why the illustration of daily fluctuations of weight measurements was useful for long-term maintenance of weight reduction. PMID- 1595776 TI - Combined therapy for obese type 2 diabetes: suppertime mixed insulin with daytime sulfonylurea. AB - Combined insulin and sulfonylurea therapy for type 2 diabetes may improve the effectiveness of a single injection of insulin, thereby postponing the need for multiple injections. This concept was tested in 21 obese subjects imperfectly controlled by 20 mg of glyburide daily in a double masked, placebo-controlled, parallel design, 16-week protocol. Premixed 70% NPH/30% Regular insulin was taken before supper, and the dosage was adjusted weekly by an algorithm seeking nearly normal fasting glycemia. Eleven subjects using insulin plus 10 mg glyburide before breakfast had lower mean fasting glucose at 10-16 weeks than 10 subjects using insulin with placebo (mean +/- SEM; 5.9 +/- 0.3 versus 7.5 +/- 0.7 mmol/L; p less than 0.05), and had a greater decrement of glycosylated hemoglobin from baseline values (1.3 +/- 0.1 versus 0.8 +/- 0.2% A1, p less than 0.05). After 16 weeks the combined therapy group used half as much insulin as the insulin-only group (50 +/- 5 versus 101 +/- 13 units/d; p less than 0.01). Fasting serum free insulin values increased 58% from baseline after insulin therapy in the insulin only group (p less than 0.05) but did not increase with combined therapy. Weight gain was similar in the two groups. These data support this form of combined therapy as one option for treating obese persons with type 2 diabetes no longer responsive to oral therapy alone. PMID- 1595777 TI - Reproducibility of the catecholamine response to serial exercise testing in normals. AB - Plasma norepinephrine (NE) and epinephrine (E) increase with exercise but the reproducibility of their response to short-term serial exercise testing has not been established. Therefore, NE and E were measured at rest, 6 minutes, peak exercise, and 5 minutes postexercise in 10 normal subjects undergoing three identical exercise tolerance tests within 4-13 days. Norepinephrine and E were also measured in tests 2 and 3 at the time equivalent to the peak exercise duration in test 1 (peak--equivalent). Exercise duration increased slightly from test 1 (15.6 +/- 0.7 min) to test 2 (16.5 +/- 0.5 min; p = 0.07) but no further on test 3 (16.2 +/- 0.9 min). Norepinephrine and E did not differ across the three tests at rest, 6 minutes, peak test or posttest, but a significant decrease in both NE and E was seen at peak-equivalent by test 3 (p less than 0.05). Heart rate decreased across the three tests at 3, 6, 9, and 12 minutes (p less than 0.02 for each) and peak equivalent (p less than 0.005) but was unchanged at rest, peak exercise and postexercise. Thus, plasma catecholamines and heart rate decrease at high levels of exercise with repeated, short-term exercise testing, possibly due to familiarity with the protocol. These results suggest that control groups are important when measuring the effects of short-term pharmacologic intervention by serial exercise tests. PMID- 1595779 TI - Case report: acute presentation of pseudo myocardial infarction secondary to metastatic cancer. AB - Electrocardiographic ST segment changes that mimic myocardial infarction (MI) may occur secondary to metastatic carcinoma. Presented here is a case in which symptomatology suggestive of acute MI occurred with impressive new anterior ST segment elevation in a patient with a history of laryngeal carcinoma. Clinical options in this setting are discussed, including use of thrombolytic agents and acute catheterization. PMID- 1595778 TI - The effect of morphine and naloxone on cocaine toxicity. AB - The effect of morphine and naloxone on acute cocaine toxicity was studied. Male Sprague-Dawley rats were pretreated intraperitoneally (ip) with saline, morphine sulfate 25 mg/kg, or naloxone 1.0 mg/kg 15 minutes prior to challenge by cocaine. After pretreatment, each group was challenged with one of three doses of cocaine (35, 50, or 75 mg/kg ip). Each of the nine drug combinations was tested on at least 10 animals. Animals were observed for behavior, seizures, and death. The animals pretreated with saline and challenged with cocaine (35, 50, or 75 mg/kg) had seizure incidences of 0%, 40%, and 100%, respectively, after increasing doses. Pretreatment with morphine resulted in cocaine-induced seizures of 20%, 80% and 100%, respectively (p less than or equal to 0.05 with cocaine 35 and 50 mg/kg). Time to seizures in these groups did not differ significantly compared to the saline groups. Pretreatment with naloxone resulted in cocaine-induced seizures of 0%, 50%, and 60% (p less than or equal to 0.05 at the 75 mg/kg dose). The incidence of death was significantly increased by pretreatment with morphine in animals that received cocaine 50 or 75 mg/kg. The time to death was not significantly different compared to saline controls. The death rate in naloxone pretreated animals was not significantly different from the saline groups. In additional studies, high-dose naloxone pretreatment (10 mg/kg) also failed to provide protection from acute cocaine toxicity. In conclusion, cocaine toxicity is potentiated by morphine and does not appear to be altered by naloxone. PMID- 1595780 TI - Case report: lymphangitic carcinomatosis from cervical carcinoma--an unusual presentation of diffuse interstitial lung disease. AB - Pulmonary lymphangitic carcinomatosis is an unusual presentation of diffuse infiltrative lung disease. In this report, we present a case secondary to cervical carcinoma that has been previously reported in only four patients. The diagnosis was made by transbronchial lung biopsy. PMID- 1595781 TI - Case report: Rhodococcus equi pneumonia in a patient infected by the human immunodeficiency virus. AB - Rhodococcus equi, a facultative intracellular bacterium, is a common cause of pulmonary infection in farm animals, especially foals. Pulmonary and disseminated infection caused by this organism is occasionally seen in humans, especially in patients whose cell-mediated immunity has been altered by glucocorticoids or cytotoxic chemotherapy. Not surprisingly, the organism may cause serious disease in human immunodeficiency virus (HIV)-infected humans whose T cell-dependent immune system has been profoundly suppressed. This report describes an HIV infected patient with Rhodococcus equi pneumonia and reviews nine additional HIV infected patients. Treatment in humans is not standardized. Studies in foals indicate that erythromycin and rifampin together are the treatment of choice. The patient in this report responded to this treatment briefly before relapsing and dying of the infection. PMID- 1595782 TI - The effect of pregnancy on renal function: physiology and pathophysiology. AB - Marked changes in renal function occur with pregnancy. We present a summary of these changes in this review and give insight into possible mechanisms if they are known. Controversies exist regarding the therapy of pregnancy-induced hypertension and asymptomatic and recurrent bacteriuria. The current views on these topics are given. Specific renal diseases are summarized, including transplantation, and optimum management strategies and maternal and fetal prognosis during pregnancy are given. PMID- 1595783 TI - Amiodarone pulmonary toxicity. AB - Amiodarone is an effective antiarrhythmic agent whose utility is limited by many side-effects, the most problematic being pneumonitis. The pulmonary toxicity of amiodarone is thought to result from direct injury related to the intracellular accumulation of phospholipid and T cell-mediated hypersensitivity pneumonitis. The clinical and radiographic features of amiodarone-induced pulmonary toxicity are characteristic but nonspecific. The diagnosis depends on exclusion of other entities, such as heart failure, infection, and malignancy. While withdrawal of amiodarone leads to clinical improvement in majority of cases, this is not always possible or advisable. Dose reduction or concomitant steroid therapy may have a role in selected patients. PMID- 1595784 TI - Resident attrition in obstetrics and gynecology. AB - OBJECTIVE: Our goal was to determine the rate of attrition from obstetrics and gynecology residency programs. STUDY DESIGN: The Council on Resident Education in Obstetrics and Gynecology sent questionnaires to all 295 obstetrics and gynecology residency program directors in the United States and Canada. These programs represent 4306 postgraduate-year 1 through 4 (or 5) resident positions each year. The program directors were asked the number of residents who left voluntarily or were dismissed in a 2-year period and the reasons they left. RESULTS: In a 2-year period 299 residents left or were dismissed (6.94% over 2 years, or 3.47% per year). Only 88 (1% per year) left specifically because they decided they preferred a different discipline. CONCLUSION: The rate of attrition from obstetrics and gynecology residency programs is not excessively high. PMID- 1595785 TI - Repeated fetal losses associated with antiphospholipid antibodies: a collaborative randomized trial comparing prednisone with low-dose heparin treatment. AB - OBJECTIVE: We attempted to compare the use of low-dose heparin with a standard dose of 40 mg prednisone daily (both plus low-dose aspirin) for treatment of pregnant women with antiphospholipid antibody-associated recurrent fetal loss with respect to maternal and perinatal morbidity and efficacy in prevention of fetal death. STUDY DESIGN: A multicenter randomized trial included 20 patients. Generalizability of results from randomized patients was evaluated by means of additional data from 13 women refusing and 12 women ineligible for randomization. Data from study groups were compared with Fisher's exact test, and generalizability was evaluated with a chi 2 test for trend. RESULTS: Live birth rates were the same (75%) with either treatment, but "serious" maternal morbidity and the frequency of preterm delivery were significantly higher among women randomly assigned to prednisone (p = 0.02 vs p = 0.006). Preterm delivery among prednisone-treated women was usually associated with premature rupture of the membranes or preeclampsia. These results could be generalized to the other groups of women ascertained during the course of the study. CONCLUSIONS: Low-dose heparin should be preferred to prednisone when treatment is indicated for high risk pregnant women with antiphospholipid antibodies. PMID- 1595786 TI - Necrotizing fasciitis of the vulva. AB - OBJECTIVE: We attempted to characterize the natural history of necrotizing fasciitis of the vulva. STUDY DESIGN: The records of 29 nonpregnant women with necrotizing fasciitis of the vulva were evaluated. RESULTS: These women experienced a rapidly progressing polymicrobial infection. Initially, the infections in many women were thought to be labial cellulitis, appearing mild and innocuous. Delays in recognition and aggressive surgical management were associated with increased morbidity and mortality. Of 15 women with a delay greater than 48 hours between presentation and treatment, 11 died. Twenty of 29 (69%) were diabetic, accounting for 11 of the 14 deaths. CONCLUSION: Early diagnosis and aggressive surgical debridement in spite of mild symptoms will improve outcome in this serious disease process. PMID- 1595787 TI - Accuracy of frozen-section diagnosis at surgery in clinical stage I and II endometrial carcinoma. AB - OBJECTIVES: The purpose of our study was to determine if frozen section accurately identifies certain poor prognostic pathologic factors in endometrial carcinoma that are known to be associated with pelvic and paraaortic nodal metastasis, including deep myometrial invasion, poorly differentiated tumor, cervical invasion, adnexal involvement, and poor histologic type. STUDY DESIGN: The frozen-section pathologic results of 199 patients with clinical stage I and II endometrial cancer were retrospectively compared with permanent-section pathologic findings. RESULTS: The depth of myometrial invasion (superficial third vs deep two thirds) was accurately determined by frozen-section diagnosis at surgery in 181 of 199 cases (91.0%). The sensitivity of frozen-section diagnosis for deep myometrial invasion was 82.7%, and the specificity was 89.1%. The following tumor characteristics were accurately determined on frozen section at surgery: poorly differentiated tumor (95.0%), cervical invasion (94.0%), adnexal involvement (98.5%), and histologic type (94.0%). Frozen section underestimated deep myometrial invasion in 17.3% of patients with this characteristic and poorly differentiated tumor in 26.3% when compared with permanent-section diagnosis. In patients with unfavorable histologic types, papillary serous and adenosquamous carcinomas were the most commonly misdiagnosed histologic types by frozen section at surgery (70.6%). However, when the preoperative curettage pathologic findings were included, these inaccuracies in tumor grade and histologic type dropped to 15.8% and 35.3%, respectively. Only 13 of 199 patients (6.5%) were not correctly identified by frozen section at surgery as having poor prognostic pathologic features. CONCLUSION: Frozen section diagnosis at surgery is an important procedure that enables the surgeon to identify patients at high risk for pelvic and paraaortic nodal metastasis. PMID- 1595788 TI - Hospitalization for pregnancy complications, United States, 1986 and 1987. AB - OBJECTIVE: The purpose of our analysis was to provide a national overview of the magnitude of the public health burden associated with inpatient care for pregnancy complications. STUDY DESIGN: We analyzed data from the National Hospital Discharge Survey for 1986 and 1987. We calculated ratios of hospitalizations for pregnancy complications for every 100 hospitalizations involving a birth. Standard errors for these ratios were calculated with RATIOEST, and relative ratios with 95% confidence intervals were calculated for subgroups of interest. RESULTS: We found that for every 100 hospitalizations involving a birth, there were 22.2 nondelivery hospitalizations for pregnancy complications (14.6 antenatal complications, 7.6 pregnancy loss complications). These ratios were higher for black than for white women (relative ratio 1.4, 95% confidence interval 1.2 to 1.6). The effects of marital status, age, and insurance coverage differed between black and white women, and mean length of stay was longer for black than for white women. CONCLUSION: Hospitalization for pregnancy complications is far more common than is widely appreciated and is more frequent among black than white women. PMID- 1595789 TI - Buserelin acetate versus expectant management in the treatment of infertility associated with minimal or mild endometriosis: a randomized clinical trial. AB - OBJECTIVE: We performed a randomized clinical trial to evaluate the efficacy of intranasal 400 micrograms buserelin three times daily for 6 months versus expectant management in the treatment of infertile women with pelvic endometriosis stage I or II of the revised American Fertility Society classification. STUDY DESIGN: Seventy-one consecutive patients (mean age 32 years) were studied at the First Department of Obstetrics and Gynecology, University of Milan, and the Department of Obstetrics and Gynecology, Ospedali Riuniti, Bergamo, between February 1988 and June 1989. Thirty-five women were randomly allocated to buserelin treatment and 36 to expectant management. The baseline distribution of subjects for age, disease stage, and reproductive history was similar in the two groups. All patients were followed regularly; median follow-up was 17 months in the buserelin group and 18 months in the women given expectant management. If pregnancy did not occur within 12 months of randomization, cycles were monitored by ultrasonography and hormone measurements, and when abnormalities were detected clomiphene citrate and human chorionic gonadotropin were administered. RESULTS: A total of 17 pregnancies were observed both in the buserelin-treated patients and in the expectant management group. The 1- and 2-year actuarial overall pregnancy rates were similar in the two groups, 30% and 61% in the former and 37% and 61% in the latter group, respectively. Spontaneous abortion occurred in five of the 17 pregnancies in the women treated with buserelin and in one of the 17 in those managed expectantly; this difference was, however, not statistically significant (chi 1(2) adjusted for disease stage and use of clomiphene citrate and human chorionic gonadotropin treatment = 3.01, p = 0.08). No fetal death or stillbirth was observed. CONCLUSIONS: Our findings suggest that treatment with gonadotropin-releasing hormone agonists is unlikely to have a marked influence on the reproductive outcome of infertile women with minimal or mild endometriosis. PMID- 1595790 TI - Magnetic cell sorting and the transferrin receptor as potential means of prenatal diagnosis from maternal blood. AB - OBJECTIVE: We wanted to test whether the recently described method of using the transferrin receptor system for fluorescence-activated cell-sorter enrichment of nucleated red blood cells can be used for prenatal diagnosis from maternal blood. STUDY DESIGN: Instead of the laborious, expensive fluorescence-activated cell sorter system, we used the newly described magnetic-activated cell sorter. RESULTS: An effective enrichment could be achieved with separation of lymphocyte subsets. With the transferrin receptor, however, the enrichment was very inefficient because of the poor specificity of the antibody itself. Even in umbilical cord blood only 25% of nucleated red blood cells were labeled as demonstrated by immunogold silver enhancement of transferrin receptor-labeled cells. CONCLUSION: In spite of the availability of a fast and effective separation method (magnetic-activated cell sorter) the use of the transferrin receptor antigen alone is not likely to enable a reliable identification of fetal cells in maternal circulation. PMID- 1595791 TI - Training obstetric and family practice residents to give smoking cessation advice during prenatal care. AB - OBJECTIVE: Our objective was to determine the effectiveness of training obstetric and family practice residents to provide smoking cessation advice. STUDY DESIGN: The effectiveness of the trained residents' advice was assessed from exit interviews of pregnant smokers taking part in a randomized, controlled trial of smoking cessation advice. Exit interview responses were compared by chi 2 analysis. RESULTS: Training resulted in significant changes in the advice provided by the residents, with greater emphasis on gaining a commitment to smoking behavior change, but not in the average time providing the advice, approximately 3 minutes. Adherence to the protocol was maintained at 80%. Significantly more women who received the brief structured advice agreed to stop smoking (54%) or cut down their cigarette consumption (28%) compared with women in the control group (14% and 6%, respectively), p = 0.0001. CONCLUSION: The structured advice consistently provided by the trained residents was effective in gaining commitments from pregnant smokers to change their smoking behavior. PMID- 1595792 TI - Changes in human fetal cerebral hemoglobin concentration and oxygenation during labor measured by near-infrared spectroscopy. AB - OBJECTIVE: The purpose of this study was to measure by near-infrared spectroscopy changes in human fetal cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume during labor and to calculate mean cerebral hemoglobin oxygen saturation. STUDY DESIGN: The effects of uterine contractions with and without fetal heart rate decelerations were compared in eight singleton term fetuses. Results were analyzed by analysis of variance. RESULTS: In six of eight fetuses normal uterine contractions were associated with proportional decreases in both oxyhemoglobin and deoxyhemoglobin and a fall in cerebral blood volume without desaturation of cerebral hemoglobin. Contractions with fetal heart rate decelerations produced different results in that oxyhemoglobin fell but deoxyhemoglobin rose, indicating cerebral desaturation. In two of the eight fetuses normal contractions were associated with increases in oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume; no decelerations were seen in either fetus. Mean cerebral hemoglobin oxygen saturation calculated during normal contractions was 43% +/- 10% (SD). CONCLUSION: Uterine contractions were associated with detectable changes from baseline in cerebral oxyhemoglobin, deoxyhemoglobin, and cerebral blood volume. PMID- 1595793 TI - Risk factors for small-for-gestational-age birth in a preterm population. AB - OBJECTIVE: The objective of this study was to discovery any distinct risk factors for small-for-gestational-age birth among premature infants. STUDY DESIGN: Demographic and obstetric risk factors were compared for 136 small-for gestational-age prematures and 636 appropriate-for-gestational-age premature infants. RESULTS: Three significant risk factors for growth retardation among premature infants were found: black maternal race (odds ratio 2.2; 95% confidence interval (1.4 to 3.5); maternal toxemia (odds ratio 3.2; 95% confidence interval 1.7 to 6.1); and either low maternal weight gain (odds ratio 4.0; 95% confidence interval 1.8 to 8.8) or missing information on maternal weight gain, which could be a marker for late or no prenatal care (odds ratio 4.9; 95% confidence interval 1.9 to 12.6). Maternal smoking rates were similar in the small- and appropriate for-gestational-age groups (42% and 43%, respectively). CONCLUSIONS: Toxemia, weight gain, and race are likely risk factors for small-for-gestational-age birth in both preterm and term populations; within the already high-risk domain of prematurity, maternal smoking did not appear to confer added risk for small-for gestational-age birth. PMID- 1595794 TI - The relationship between acute inflammatory lesions of the preterm placenta and amniotic fluid microbiology. AB - OBJECTIVE: Our objective was to determine the relationship between microbial invasion of the amniotic cavity and the presence and severity of acute inflammatory lesions in the placenta. STUDY DESIGN: Placental histologic and amniotic fluid microbiologic studies were performed in 92 consecutive patients who were admitted with preterm labor and intact membranes and delivered within 48 hours after amniocentesis. RESULTS: The prevalence of a positive amniotic fluid culture was 38% (35 of 92). There was a strong association between the presence and severity of inflammation in the amnion, chorion-decidua, umbilical cord, and chorionic plate and the results of the amniotic fluid culture (p less than 0.0001 for each tissue section). Three patterns of inflammation of the chorion-decidua were identified: marginating, nonmarginating, and a mixed pattern. The marginating and the mixed patterns of inflammation were strongly associated with the presence of a positive amniotic fluid culture. Acute inflammation of the chorionic plate was the most sensitive indicator of a microbial invasion of the amniotic cavity (sensitivity 96.6%), and funisitis and umbilical vasculitis had the highest specificity (85.7%). CONCLUSION: The presence of acute inflammatory lesions of the chorioamniotic membranes can serve as a marker of microbial invasion of the amniotic cavity. PMID- 1595795 TI - Ultrastructure of the microvasculature in the human endometrium throughout the normal menstrual cycle. AB - In the early proliferative phase endometrial capillary basal lamina is loosely formed and discontinuous. It becomes more distinct in the late proliferative phase and develops whorled extensions that include pericytes in the early secretory to midsecretory phase. Throughout the cycle both endothelial cells and pericytes possess cytoplasmic processes that extend through discontinuities in the basal lamina and make contact with each other. These contacts may be simple or complex. They become more elaborate as the cycle progresses to the midsecretory phase. Endothelial cells show progressive but heterogeneous differentiation into the midsecretory phase, with individual cell hypertrophy. In the late-secretory phase the endometrial stroma and the basal lamina are characterized by widespread degeneration, and the cell-to-cell contacts sharply decrease. However, endothelial cells remain relatively intact. PMID- 1595796 TI - Infertility and pregnancy outcome in an unselected group of women with insulin dependent diabetes mellitus. AB - OBJECTIVES: The null hypothesis of this study is that infertility and pregnancy outcomes in women with insulin-dependent diabetes are identical to those of nondiabetic control subjects. STUDY DESIGN: A questionnaire survey comprising an unselected population of 18- to 49-year-old diabetic women and a comparable control group was performed. Reply rates were 94% (n = 245) and 88% (n = 253), respectively. RESULTS: Cumulative rates of pregnancies and involuntary infertility (17%) did not differ between the two groups. Diabetic women had significantly fewer pregnancies (1.4 vs 1.7) and fewer births per pregnancy than controls, and more diabetic women were nulliparous (48% vs 38%). Half of all diabetic pregnancies were planned. Diabetic women reported that their diabetes had a negative influence on their attitude toward having children. CONCLUSION: In insulin-dependent diabetic women the ability to conceive is normal, but diabetic women have fewer pregnancies and fewer births per pregnancy than controls. PMID- 1595797 TI - Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia. AB - Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction. PMID- 1595799 TI - Human fetal bilirubin levels and fetal hemolytic disease. AB - The development of secondary fetal anemia in association with maternal red blood cell alloimmunization requires hemolysis. In specimens obtained at the time of a clinically indicated cordocentesis, total and direct umbilical venous bilirubin was measured and the indirect umbilical venous bilirubin calculated in 43 antigen positive and 30 control fetuses. Twenty-two (51%) of the antigen-positive fetuses had or subsequently developed severe anemia (hematocrit less than 30%). Umbilical venous total bilirubin (r = 0.47, p = 0.0008) and direct bilirubin (r = 0.520, p = 0.04) levels each rose with gestation. Indirect bilirubin did not vary significantly with gestation. Bilirubin was unrelated to hemoglobin. In contrast to the control fetuses, umbilical venous total bilirubin for antigen-positive fetuses was inversely related to hemoglobin (r = -0.57, p less than 0.0001) independent of gestational age (r = 0.53, p less than 0.0001) (multiple R of hemoglobin and gestational age for umbilical venous total bilirubin = 0.76, p less than 0.0001). Eighteen of 22 (82%) fetuses in whom anemia developed had an umbilical venous total bilirubin greater than or equal to 97.5 percentile compared with only eight of 21 (38%) fetuses in whom anemia did not develop (p = 0.009). In longitudinal study the umbilical venous total bilirubin frequently rose above normal weeks before the development of anemia. An umbilical venous total bilirubin greater than 3 mg/dl represented the warning line. Fifteen of 16 (94%) fetuses in whom either severe antenatal anemia or significant postnatal hyperbilirubinemia developed had an umbilical venous total bilirubin greater than 3 mg/dl. We conclude that the normal placental capacity for the transport of fetal bilirubin is exceeded in the face of enhanced fetal hemolysis. An elevated fetal bilirubin often precedes the development of antenatal anemia. The antigen positive fetus with an elevated bilirubin is at high risk to develop anemia antenatally. PMID- 1595798 TI - Elevated plasma Met-enkephalin levels in the human newborn are a poor indicator of perinatal stress. AB - OBJECTIVE: This study was designed to investigate whether plasma Met-enkephalin peptides could serve as markers of physiologic stress in the neonate. STUDY DESIGN: Infants (n = 115) between 1.2 and 4.7 kg and 28 and 42 weeks of gestation were studied at birth. Seventy-four infants were delivered by the vaginal route, 31 by cesarean section after labor, and 10 by cesarean section before labor. Correlations were sought between plasma enkephalin peptides and epinephrine, norepinephrine, and arterial blood gases with linear regression analysis. Various clinical data were also analyzed. RESULTS: Plasma Met-enkephalin levels were significantly greater in infants exposed to labor (440 +/- 36 vs 260 +/- 30 pg/ml, p less than 0.05). The large-molecular-weight forms of enkephalin peptides were also greater in these infants (approximately 50 +/- 4 vs 23 +/- 2 ng/ml). There was no correlation between plasma enkephalin peptides and catecholamines, arterial pH, or Apgar scores. There was a significant but weak correlation between plasma Met-enkephalin levels and birth weight (r = 0.34, p = 0.03) and PaO2 (r = -0.28, p less than 0.05). CONCLUSION: The lack of correlation between Met-enkephalin plasma levels and umbilical plasma catecholamine concentrations, acid-base status, or Apgar scores suggests that circulating Met-enkephalin is a poor indicator of stress in the newborn. PMID- 1595800 TI - Acute genital injury in the prepubertal girl. AB - In an effort to develop guidelines for the management of acute genital injuries in prepubertal girls, we categorized 32 cases by the object that allegedly caused the injury: straddle injuries, nonpenetrating injuries, penetrating injuries, and torque injuries. Using these categories and the anatomic features of symmetry and/or hymenal transection, we determined that the most dangerous injuries were the penetrating injuries that were symmetric and transected the hymen; in this series these were all the result of sexual assault. Future studies are needed to determine if these unique injuries can be managed with less physical and psychosocial trauma to the young patient. PMID- 1595801 TI - The use of a neural network for the ultrasonographic estimation of fetal weight in the macrosomic fetus. AB - The error associated with regression analysis methods for the ultrasonographic estimation of fetal weight in the suspected macrosomic fetus, approximately 10%, is clinically unacceptable. This study was undertaken to evaluate the applicability of an emerging technique, biologically simulated intelligence, to this problem. One hundred patients with suspected macrosomic fetuses underwent ultrasonographic measurements of biparietal diameter, head and abdominal circumference, femur length, abdominal subcutaneous tissue, and amniotic fluid index. The biologically simulated intelligence model included gestational age, fundal height, age, gravidity, and height. The model was then compared with results obtained from previously published formulas relying on the abdominal circumference and femur length. The biologically simulated intelligence yielded an average error of 4.7% from actual birth weight, statistically better (p = 0.001) than the results obtained from regression models. PMID- 1595802 TI - Fetal echocardiography: accuracy and limitations in a population at high and low risk for heart defects. AB - OBJECTIVE: Our objective was to assess the accuracy of prenatal echocardiography in detecting congenital heart defects in patients at high and low risk for structural cardiac anomalies. STUDY DESIGN: Sixty-nine consecutive fetuses with congenital heart defects who had had prenatal ultrasonography at greater than or equal to 18 weeks' gestation were evaluated to determine the accuracy of prenatal ultrasonography in identifying structural cardiac defects. Thirty-nine patients were at high risk and 30 patients were at low risk for cardiac anomalies. All fetuses were scanned with standard four-chamber and outflow tract views. Data concerning extracardiac anomalies and karyotypic abnormalities were tabulated. The accuracy of the four-chamber view alone in identifying congenital heart defects was evaluated. RESULTS: Fifty-seven of 69 fetuses (83%) were prenatally identified ultrasonographically as having a heart defect. There was no difference in the sensitivity of detecting cardiac anomalies between high-risk and low-risk groups. When the four-chamber view was used, only 63% of fetuses were recognized as having an abnormal heart. Extracardiac anomalies were noted in 36% and karyotypic abnormalities in 17% of patients. CONCLUSION: The four-chamber and outflow tract views done routinely in an ultrasonography laboratory seeing a mixed population of patients was successful in detecting 83% of fetuses with structural cardiac malformations. Because 43% of the fetuses with heart defects were referred for low-risk indications, systematic ultrasonographic examination of the fetal heart should not be reserved only for those at high risk. PMID- 1595803 TI - In situ and invasive vulvar cancer incidence trends (1973 to 1987). AB - OBJECTIVE: The objective of this study was to examine recent trends in the incidence of vulvar cancer. STUDY DESIGN: Cases of in situ and invasive squamous cell vulvar cancer were identified from nine Surveillance, Epidemiology, and End Results cancer registries. RESULTS: The incidence rate of in situ vulvar cancer nearly doubled between 1973 to 1976 and 1985 to 1987, whereas the rate of invasive squamous cell carcinoma remained relatively stable. CONCLUSIONS: Possible reasons for this discordance include the following: (1) Women affected by the "sexual revolution" are not yet old enough to have invasive vulvar carcinoma; (2) early diagnosis and treatment of in situ carcinoma have mitigated anticipated increases in invasive vulvar carcinoma incidence; (3) in situ and invasive carcinomas of the vulva have different etiologies, with the sexually transmitted human papillomavirus involved in the etiology of in situ carcinoma and other factors involved with most invasive squamous cell carcinoma. PMID- 1595804 TI - Comprehensive fetal assessment with three ultrasonographic characteristics. AB - OBJECTIVES: When three ultrasonographic characteristics--umbilical artery Doppler recording, growth (abdominal circumference), and biophysical profile score--are used in combination in assessment of fetuses at risk of chronic asphyxia: (1) What are the order and time scale for the development of abnormality with each characteristic? (2) What is the short-term outcome associated with abnormalities of the three characteristics? (3) Should we amend our fetal assessment protocol? STUDY DESIGN: An audit of 103 fetuses (100 mothers) referred to a tertiary center for fetal assessment because of suspected chronic fetal asphyxia was performed with three ultrasonographic characteristics, umbilical artery Doppler recording, measurement of abdominal circumference, and documenting the biophysical profile score. RESULTS: The order of deterioration (which had a very variable time scale) was umbilical artery Doppler recording, followed by abdominal circumference and finally biophysical profile score. Normal characteristics or an abnormal umbilical artery Doppler recording alone or an abnormal abdominal circumference alone was associated with an excellent prognosis. The worst outcome was found in the 28 fetuses with abnormality of all three ultrasonographic features before delivery. CONCLUSIONS: The main suggested implications for management are avoidance of preterm delivery with normal ultrasonographic characteristics, an abnormal umbilical artery Doppler recording alone, or an abnormal abdominal circumference alone; delivery of fetuses at greater than or equal to 34 weeks with abnormal umbilical artery Doppler recording and abdominal circumference before the biophysical profile score becomes abnormal; and implementation of specific measures to prevent necrotizing enterocolitis in newborns when all three characteristics are abnormal. PMID- 1595805 TI - A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy. AB - OBJECTIVE: Our objective was to develop a mathematic model for the prediction of transvaginal ultrasonographic identification of intrauterine gestation as a function of human chorionic gonadotropin titer or gestational age. STUDY DESIGN: In this prospective, descriptive study normal intrauterine pregnancies of 31 patients from the Yale in vitro fertilization and embryo transfer program and infertility clinic were studied. Logistic regression analysis was used to develop a probability curve of transvaginal ultrasonographic detection of intrauterine pregnancy as a function of human chorionic gonadotropin titer or gestational age with a 5 MHz vaginal transducer. RESULTS: A model-based prediction was constructed. It revealed that nearly all intrauterine sacs should be identified by a human chorionic gonadotropin titer of 3000 mIU/ml (first international reference preparation) or by a gestational age of 37 days on the basis of the 5 MHz vaginal transducer. CONCLUSIONS: A model-based prediction for transvaginal ultrasonographic identification of early intrauterine pregnancy is presented that can be readily adapted by individual institutions using their own ultrasonographic equipment and human chorionic gonadotropin assay. PMID- 1595806 TI - Comparison of adenocarcinoma and squamous cell carcinoma of the uterine cervix: a population-based epidemiologic study. AB - OBJECTIVE: Our objective was to compare epidemiologic and clinical characteristics of adenocarcinoma with those of squamous cell carcinoma of the cervix, with respect to risk by ethnic group, age at diagnosis, stage of disease at diagnosis, and survival. STUDY DESIGN: All data were obtained from the Cancer Surveillance Program of Orange County, California, from 1984 through 1989. A total of 152 cases of adenocarcinoma and 457 of squamous cell carcinoma of the uterine cervix were included. RESULTS: Adenocarcinoma of the cervix was diagnosed at a younger age and an earlier stage than squamous cell carcinoma. Hispanics have the highest risk for squamous cell carcinoma, whereas Asians have the highest risk for adenocarcinoma compared with whites. No differences were observed between the two histologic types in prognosis and survival. CONCLUSION: Differences between the two histologic types of cervix cancer were found in the age at diagnosis, the extent of disease, and the ethnic distribution. In spite of these differences, prognosis and survival were not affected by histologic type. PMID- 1595807 TI - A review of premature birth and subclinical infection. AB - Premature birth causes high rates of neonatal morbidity and mortality. There are multiple causes of preterm birth. This article reviews the evidence linking subclinical infection and premature birth. Although maternal genital tract colonization with specific organisms has been inconsistently associated with preterm birth and/or premature rupture of membranes, some infections have been consistently associated with preterm delivery. The association of histologic chorioamnionitis with prematurity is a consistent finding, but the mechanisms require further study. The relationship between histologic chorioamnionitis infection and the chorioamnionitis of prematurity requires additional research. A varying number of patients in "idiopathic" preterm labor have positive amniotic fluid cultures (0% to 30%), but it is not clear whether infection preceded labor or occurred as a result of labor. Evidence of subclinical infection as a cause of preterm labor is raised by finding elevated maternal serum C-reactive protein and abnormal amniotic fluid organic acid levels in some patients in preterm labor. Biochemical mechanisms for preterm labor in the setting of infection are suggested by both in vitro and in vivo studies of prostaglandins and their metabolites, endotoxin and cytokines. Some, but by no means all, antibiotic trials conducted to date have reported decreases in prematurity. These results support the hypothesis that premature birth results in part from infection caused by genital tract bacteria. In the next few years, research efforts must be prioritized to determine the role of infection and the appropriate prevention of this cause of prematurity. PMID- 1595809 TI - The effect of benzo(a)pyrene on murine ovarian and corpora lutea volumes. AB - OBJECTIVE: Women who smoke have impaired fertility and experience menopause at an earlier age. This experiment determined the effect of benzo(a)pyrene, a polycyclic aromatic hydrocarbon contained in cigarette smoke, on murine ovarian volume, total corpora lutea volume, individual corpora lutea volumes, and corpora lutea numbers. STUDY DESIGN: C57BL/6N mice were treated with intraperitoneal injections of 0 to 500 mg/kg benzo(a)pyrene in corn oil. The 20 mice at each dose were divided into four groups of five each and were killed at 1, 2, 3, or 4 weeks after treatment. Ovaries were serially sectioned and analyzed morphometrically. RESULTS: Benzo(a)pyrene produced a dose- and time-dependent decrease in ovarian volume, total corpora lutea volume, and number of corpora lutea per ovary. This effect was transitory at low doses with complete recovery of corpora lutea by 4 weeks. Compensatory hypertrophy of the individual corpora lutea occurred during the recovery phase. Ovarian function did not return in animals treated with the two highest doses. CONCLUSION: Benzo(a)pyrene is a murine ovarian toxicant that inhibits corpus luteum formation in a dose- and time-dependent fashion. PMID- 1595808 TI - In the rhesus monkey placental retention after fetectomy at 121 to 130 days' gestation outlasts the normal duration of pregnancy. AB - OBJECTIVE: Our aim was to reassess the role of the fetus in the initiation of parturition in nonhuman primates. We tested the effect of the removal of the fetus at 121 to 130 days' gestation on the duration of gestation in pregnant rhesus monkeys. STUDY DESIGN: Nine monkeys underwent fetectomy with the placenta in situ. Five monkeys underwent surgery without removal of the fetus. RESULTS: In five control monkeys spontaneous vaginal delivery of live fetuses occurred at 163.8 +/- 4.6 days' gestation (mean +/- SD). In four of nine monkeys that underwent fetectomy the placenta delivered spontaneously at 185, 193, 201, and 207 days' gestation. The five remaining monkeys underwent cesarean section at 162, 189, 201, 202, and 219 days' gestation. Duration of placental retention in monkeys that underwent fetectomy (195 +/- 16.1 days' gestation) exceeded that in controls (p less than 0.05). Plasma progesterone and estradiol concentrations were normal for gestational age at fetectomy, indicating continued placental function. CONCLUSION: We conclude that the presence of a live fetus plays a significant role in the determination of the duration of normal pregnancy in the rhesus monkey. PMID- 1595810 TI - The mechanisms of preterm labor: common genital tract pathogens do not metabolize arachidonic acid to prostaglandins or to other eicosanoids. AB - OBJECTIVE: Our aim was to determine the ability of pathogens commonly associated with genital tract infection and preterm labor to incorporate arachidonic acid and to metabolize it to prostaglandins or to other eicosanoids. STUDY DESIGN: Four common genital tract pathogens, Escherichia coli, Streptococcus viridans, Bacteroides fragilis, and a group B beta-hemolytic streptococcus, were incubated with tritium-labeled arachidonic acid for 2 to 48 hours. Uptake of arachidonic acid was calculated from uptake of radioactivity into the organisms. Tritium labeled arachidonic acid within the medium was separated from any metabolites by high-performance liquid chromatography to assess metabolism of arachidonic acid within the bacteria. RESULTS: Although all organisms were able to take up arachidonic acid, analysis of its metabolism with high-performance liquid chromatography demonstrated that none of these organisms will synthesize cyclooxygenase, lipoxygenase, or epoxygenase products. CONCLUSION: Bacterial infection cannot initiate preterm labor by intrinsic biosynthesis and release of prostaglandins or other eicosanoids by the bacteria themselves. PMID- 1595811 TI - Renal autoregulation in midterm and late-pregnant rats. AB - OBJECTIVES: The normal kidney autoregulates (that is, maintains) renal blood flow over a wide range of arterial blood pressures. During normal pregnancy blood pressure falls and the kidney vasodilates. The purpose of this study was to investigate whether renal autoregulatory ability was influenced during pregnancy in the normal rat. STUDY DESIGN: Experiments were conducted on three groups of anesthetized rats, studied in the virgin state, at midterm, and late in pregnancy (gestation lasts 22 days in the rat). Renal blood flow was measured by electromagnetic flow probe at normal renal perfusion pressures, during elevation in renal perfusion pressure with bilateral carotid occlusion, and at subnormal renal perfusion pressures after application of an aortic snare. RESULTS: Blood pressure was similar in midterm and virgin rats but lower in late pregnancy in the control state. Control renal blood flow was similar between virgin and late pregnant rats but significantly elevated at midterm. During elevation in blood pressure with bilateral carotid occlusion, autoregulation was maintained in all three groups. During graded aortic occlusion, renal autoregulatory ability was lost. The autoregulatory threshold was between 90 and 100 mm Hg for midterm pregnant and virgin rats and was slightly lower at about 88 mm Hg for late pregnant rats. CONCLUSIONS: Midterm pregnant rats are able to autoregulate renal blood flow as well as virgins are in spite of underlying gestational renal vasodilation. The slight shift in renal autoregulatory threshold seen in late pregnant rats may prevent the kidney from hypoperfusion during late-gestation hypotension. PMID- 1595812 TI - Effects of antenatal thyrotropin-releasing hormone, antenatal corticosteroids, and postnatal ventilation on surfactant mobilization in premature rabbits. AB - OBJECTIVE: The effects of antenatal hormones on postnatal surfactant mobilization were evaluated in preterm rabbits. STUDY DESIGN: Pregnant rabbits were treated with vehicle, betamethasone, or thyrotropin-releasing hormone for 2 days before cesarean section at 29 days' gestation (term 31 days). Newborns were mechanically ventilated or allowed to spontaneously breathe, and groups were compared by analysis of variance. RESULTS: Neither antenatal corticosteroids nor thyrotropin releasing hormone increased radiolabeled precursor incorporation, alveolar wash or total lung saturated phosphatidylcholine pools, lung clearance of radiolabeled rabbit surfactant, or estimated net secretion of saturated phosphatidylcholine. However, saturated phosphatidylcholine pools in alveolar wash increased 2.7-fold during the first 24 hours in spontaneously breathing rabbits versus 2.1-fold in mechanically ventilated thyrotropin-releasing hormone-treated and control rabbits (p less than 0.05). In addition, estimated net secretion of precursor-derived saturated phosphatidylcholine was 50% higher after 24 hours in spontaneously breathing rabbits. CONCLUSION: Mechanical ventilation may have hindered the mobilization of surfactant saturated phosphatidylcholine pools to the alveolar space after birth in preterm rabbits, but maternal hormonal therapies did not appear to influence this adaptive process or change surfactant metabolism. PMID- 1595813 TI - N omega-nitro-L-arginine, an inhibitor of nitric oxide synthesis, increases blood pressure in rats and reverses the pregnancy-induced refractoriness to vasopressor agents. AB - OBJECTIVE: With N omega-nitro-L-arginine, a potent inhibitor of nitric oxide synthesis, we tested the hypothesis that nitric oxide plays a functional role in the blunted pressor responsiveness seen during pregnancy. STUDY DESIGN: A group of six pregnant rats were instrumented on the fourteenth day of gestation and studied on days 19 and 20, as well as 7 days post partum. Another group of six virgin rats were similarly prepared and used 5 days after surgery. Blood pressure and heart rate were monitored in conscious freely moving animals before and during the administration of drugs or placebo. Results were analyzed, by one-way repeated-measures analysis of variance, with Dunnett's t test, or by paired t test where applicable. RESULTS: Basal mean arterial pressure and heart rate were 90.8 +/- 3.0 mm Hg and 330 +/- 6 beats/min in pregnant animals and 107.1 +/- 3.2 mm Hg and 315 +/- 7 beats/min in nonpregnant animals. Pressor responses to angiotensin II, vasopressin, and norepinephrine were attenuated in gravid animals. Infusion of N omega-nitro-L-arginine significantly and in a dose dependent manner increased mean arterial pressure and reduced heart rate. These effects could be completely reversed by L-arginine administration. Changes in mean arterial pressure were higher during pregnancy as compared with postpartum values. N omega-nitro-L-arginine infusion potentiated pressor responses to all three vasopressors, resulting in dose-response curves that were significantly shifted to the left, making them virtually identical in pregnant and postpartum rats. CONCLUSION: Our data support the emerging view that nitric oxide plays a key role in the regulation of blood pressure during pregnancy. PMID- 1595814 TI - Role of prostaglandins in the metabolic responses of the fetus to hypoxia. AB - OBJECTIVE: The effect of inhibiting prostaglandin synthesis on the fetal metabolic response to hypoxemia was examined by infusing indomethacin during periods of reduced maternal uterine blood flow. STUDY DESIGN: In seven fetal sheep we administered a 6-hour infusion of either indomethacin (n = 5), indomethacin plus prostaglandin E2, or a vehicle solution (n = 5). The last 4 hours of each infusion period coincided with a period of fetal hypoxemia induced by reduced maternal uterine blood flow. RESULTS: During reduced maternal uterine blood flow indomethacin infusions caused a significantly greater reduction in pHA (reduced from 7.36 +/- 0.01 to 7.10 +/- 0.02) than both the vehicle (from 7.36 +/ 0.01 to 7.20 +/- 0.03) and indomethacin plus prostaglandin E2 infusions (from 7.36 +/- 0.01 to 7.18 +/- 0.02). Before reduced maternal uterine blood flow was induced, indomethacin significantly elevated fetal plasma glucose and lactate concentrations from 0.6 +/- 0.04 and 2.2 +/- 0.1 to 1.3 +/- 0.2 and 6.7 +/- 0.7 mmol/L, respectively. During reduced maternal uterine blood flow indomethacin caused a significantly greater increase in plasma glucose and lactate concentrations than the vehicle; plasma glucose and lactate concentrations increased to a maximum of 1.8 +/- 0.2 and 22.7 +/- 0.8 mmol/L, respectively, during indomethacin infusions compared with 1.1 +/- 0.1 and 15.7 +/- 1.7 mmol/L, respectively, during vehicle infusions. The addition of prostaglandin E2 to the indomethacin infusion prevented the enhanced increase in glucose and lactate concentrations during reduced maternal uterine blood flow and caused a significant increase in fetal plasma insulin concentrations from 12.6 +/- 0.7 to 60.9 +/- 28.1 microU/ml. CONCLUSION: The inhibition of prostaglandin synthesis during fetal hypoxemia alters the metabolic response of the fetus, leading to a severe metabolic acidosis. PMID- 1595816 TI - The issue of animal rights and human rights. PMID- 1595815 TI - Tumor necrosis factor in preterm and term labor. AB - OBJECTIVE: Our objective was to determine if labor (term and preterm) and microbial invasion of the amniotic cavity were associated with changes in amniotic fluid concentrations of tumor necrosis factor. STUDY DESIGN: Amniotic fluid was retrieved by transabdominal amniocentesis from 269 women in the following groups: midtrimester (n = 38), preterm labor with intact membranes (n = 52), preterm premature rupture of membranes (n = 74), term in active labor (n = 84), and term not in labor (n = 21). Fluid was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. Tumor necrosis factor was measured with a commercially available enzyme-linked immunosorbent assay validated for amniotic fluid (sensitivity 60 pg/ml). RESULTS: Amniotic fluid from pregnant women in the second and third trimesters who were not in labor did not contain tumor necrosis factor. Among women in preterm labor, 92.3% (12/13) of patients with a positive amniotic fluid culture had detectable tumor necrosis factor in the amniotic fluid (median 820 pg/ml, range less than 60 to 2340 pg/ml). In contrast, only 10.2% (4/39) of women with a negative amniotic fluid culture had detectable tumor necrosis factor. Histopathologic chorioamnionitis was found in all patients who had a positive amniotic fluid culture, and tumor necrosis factor was detectable in the amniotic fluid of all but one of these patients. Among women in active labor at term, 25% (21/84) had detectable tumor necrosis factor in the amniotic fluid. Tumor necrosis factor was detected more frequently in the amniotic fluid of patients with a positive amniotic fluid culture than in patients with a negative culture (46.6% [7/15] vs 20.2% [14/69], p = 0.047). Amniotic fluid concentrations of tumor necrosis factor were significantly higher in patients with preterm premature rupture of membranes, labor, and a positive amniotic fluid culture than in the other subgroups of patients with preterm premature rupture of membranes. CONCLUSION: Parturition in the setting of microbial invasion of the amniotic cavity is associated with activation of the cytokine network as demonstrated by the detection of tumor necrosis factor in human amniotic fluid. PMID- 1595817 TI - Fetal biophysical and umbilical cord gases. PMID- 1595818 TI - Hemolytic disease of the fetus. PMID- 1595819 TI - Ovarian cancer screening. PMID- 1595820 TI - Epidermal growth factor receptor expression in cervical intraepithelial neoplasia. PMID- 1595821 TI - Occupational therapy intervention with the alcoholic's family. AB - In this paper, the role of occupational therapy in the treatment of the family affected by alcoholism is explored. Literature is reviewed to analyze occupational therapists' current approaches for interacting with the family. A family-treatment approach, based on systems theory, is organized into three hierarchical treatment levels that accommodate the family's maladaptive roles. Family treatment methods thought most likely to produce the desired results are delineated according to treatment level. Treatment Level 1 focuses on reduction of maladaptive role behaviors of the family that enable the person's drinking. At Treatment Level 2, family members are taught coping skills that weaken their reliance on maladaptive roles. Emotional development is stimulated at Treatment Level 3 through confrontation of continued use of maladaptive roles. PMID- 1595822 TI - Tell me a story: the therapeutic metaphor in the practice of pediatric occupational therapy. AB - In the crafting of therapeutic intervention, pediatric occupational therapists are challenged to provide therapeutic modalities that are as stimulating and imaginative as the child's world, while offering appropriate and meaningful solutions to the child's problems. Storytelling, coupled with the visual, auditory, and kinesthetic stimulation of guided affective imagery, offers a stimulating treatment approach for both the child or adolescent and the occupational therapist. This paper provides an overview of the use of storytelling, metaphorical forms and expressions, and guided affective imagery in occupational therapy with children. PMID- 1595823 TI - A comparison of performance measures of an added-purpose task versus a single purpose task for upper extremities. AB - Occupational therapists often employ multidimensional tasks. These tasks, referred to as added-purpose tasks, provide a person with necessary exercise, yet direct the focus of attention toward another objective or outcome. The assumption is that the additional purpose will result in improved task performance, provided it is sufficiently distracting or meaningful to the person. The present study examined the effects of an added-purpose task compared with a single-purpose task on performance, as measured by the number of repetitions, task duration, and exercise heart rate. Thirty subjects performed either the added-purpose task or the single-purpose task three times during a 2-week period. Each session was terminated when the subject reported that he or she was exercising at a "very hard" rate on a measure of perceived exertion. A multiple analysis of variance for repeated measures indicated no significant difference between the performance of the subjects in the added-purpose versus the single-purpose task group on any of the dependent measures. Solicitation of patients' assessment of the value and meaningfulness of the rehabilitative task has practical importance. PMID- 1595824 TI - Comparative effects of bilateral hand splints and an elbow orthosis on stereotypic hand movements and toy play in two children with Rett syndrome. AB - A single-subject rapidly alternating treatment design was used to compare the effectiveness of bilateral hand splints and an elbow orthosis in decreasing stereotypic hand behaviors and increasing toy play in 2 children with Rett syndrome. The subjects' responses were compared across three treatment conditions: no intervention, hand splints, and elbow orthosis. The order of the treatment phases was randomly selected for each subject. Data were collected in both a free-time condition and a toy-play condition; the outcome measures were stereotypic hand movements and hand-to-toy contact. Both subjects demonstrated a decrease in stereotypic hand movements and a corresponding increase in toy contact with the use of the elbow orthosis. The bilateral hand splints had no obvious treatment effect. PMID- 1595825 TI - Occupational therapy treatments for constructional deficits. AB - Occupational therapists use both adaptive and remedial approaches to perceptual retraining in adults with head injury. This experimental treatment outcome study compared the effects of adaptive and remedial treatments for constructional deficits on meal preparation competence and on constructional abilities in adult men with head injury. Forty-five subjects, 18 to 52 years of age, in long-term rehabilitation programs were randomly assigned to one of two treatment groups. A remedial group (n = 22) received individual training with parquetry block assembly, and an adaptive group (n = 23) received individual training in food preparation activities. Both groups received training for three 30-min sessions per week for 6 weeks, in addition to their regular rehabilitation programs. Results of analyses of variance and paired t tests on perceptual and functional test scores showed task-specific learning in both groups and suggested that training in functional activities may be the better way to improve performance in such activities in this population. PMID- 1595826 TI - Hand splinting in quadriplegia: current practice. AB - A mailed survey was conducted to collect information about the application of hand splints to patients with spinal cord injuries resulting in quadriplegia at levels C-5, C-6, C-7, and C-8. Survey respondents were occupational therapists in spinal cord injury centers nationwide. Frequency and descriptive statistics were collected concerning both static and dynamic splints, the clinical reasoning behind splint selection, and methods used for the evaluation of hand function. The results of the survey indicate that hand splinting is an accepted intervention for the target population. A variety of static splint designs were used, depending on level of injury, muscle strength, and the patient's acceptance. The dynamic splint designs were used most frequently with patients whose lesions were at C-6 and C-7. The reasons for not splinting were primarily related to the patient's compliance and acceptance. Observation of patients' performance of functional tasks was the preferred method of evaluation of hand function, as there are no appropriate standardized tests available for this population. PMID- 1595827 TI - Instructing occupational therapy students in information retrieval. AB - The effectiveness of a brief program designed to teach occupational therapy students enrolled in a graduate research methods class to conduct searches of four electronic databases was investigated. Students in the experimental class read an instructional booklet and received approximately 1 hour of supervised practice time using compact disk--read-only memory (CD-ROM) equipment. Questionnaire data revealed that compared with the students in the control class, the students completing the training program reported being significantly more familiar with six of seven key concepts and indicated significantly higher levels of usage of the four databases studied in the program. PMID- 1595828 TI - Selecting a pressure-relief training device. PMID- 1595829 TI - Specialization or uniformity within the profession? PMID- 1595830 TI - The role of occupational therapy in the management of depression. AB - This document was prepared at the request of the Depression Panel of the Office of the Forum for Quality and Effectiveness in Health Care within the Agency for Health Care Policy and Research, an agency of the U.S. Public Health Service. The panel was charged to develop clinical practice guidelines for the management of depression to be used by general medical and family medicine practitioners in primary care settings. The form of the panel's questions shaped the introductory portion of the document. After receiving the questions posed by the panel (which are stated later in this document), it was necessary to define the context of the use of occupation and occupational therapy to broaden the panel's understanding of these terms. PMID- 1595831 TI - Functional measures, Part 1: What is function, what should we measure, and how should we measure it? PMID- 1595832 TI - Issue on clinical reasoning lacks papers on mental health. PMID- 1595833 TI - Spearman correlations of .60 are not poor. PMID- 1595834 TI - Extended resection for locally advanced colorectal carcinoma. AB - We reviewed the medical records of 101 patients who underwent extended resection for locally advanced colorectal carcinoma between 1965 and 1989. Preoperative symptoms related to the genitourinary system were present in 46 patients. Malignant invasion of genitourinary structures by colorectal carcinoma was found in 43 of these 46 patients (93%). In contrast, 51% of the patients without such symptoms had malignant invasion of contiguous structures. Preoperative intravenous pyelography, computerized tomographic scans, and cystoscopy correctly predicted the presence or absence of malignant invasion in 89%, 83%, and 87% of patients, respectively. Tumor-positive resection margins had a negative impact on survival (mean survival: 11.4 months). The 5-year actuarial survival rate for the patients who underwent a curative extended resection (margins tumor negative) was 54%. A thorough preoperative evaluation can identify a significant number of patients with colorectal cancer extending into adjacent organs and structures. Such evaluation is vital for operative planning and patient preparation, since an appropriate extended resection can produce long-term local control and patient survival. PMID- 1595835 TI - Efficacy of preadmission testing in ambulatory surgical patients. AB - A retrospective study was done with 325 patients who had preadmission testing prior to ambulatory surgery. At least one laboratory abnormality was noted in 84% of the patients. The serial multiple analysis (SMA)-7 was abnormal 63% of the time. Abnormalities were seen in 54% of the SMA-12 panels and 38% of the urinalyses performed. Twenty-four percent of the patients treated had an abnormal electrocardiogram (ECG). An abnormal chest roentgenogram was found in 19% of the patients. Only three (1%) patients potentially benefited from preadmission testing. Ninety-six percent of the abnormal laboratory results were ignored by the attending physicians. Therefore, we conclude that preadmission testing should be done on a selective basis. Patients older than 50 years of age should have an ECG. A hematocrit should be obtained only if major blood loss is anticipated. All other tests should be ordered based on the history and physical examination. PMID- 1595836 TI - Postoperative chemotherapy for patients with advanced gastric cancer. AB - The relationship between postoperative chemotherapy and survival time after gastric resection in patients with advanced gastric cancer was examined by retrospectively reviewing data on 916 patients treated in our clinics between 1965 and 1985. Of these patients, 738 were treated postoperatively with antitumor drugs. Postoperative chemotherapy was more often prescribed for those in the advanced stages of malignancy. Univariate analysis revealed that the survival time of patients given postoperative chemotherapy was shorter than for those not receiving chemotherapy, but there was no statistical significance. Multivariate analysis using the Cox regression analysis adjusted for sex, age, and other covariants indicated that operative curability, liver metastasis, serosal invasion, lymph node metastasis, peritoneal dissemination, and tumor size were the important prognostic factors. There was no correlation with postoperative chemotherapy. Our findings rule out any relationship between postoperative chemotherapy and length of survival time for patients with advanced gastric cancer undergoing gastric resection. PMID- 1595837 TI - Gastroesophageal physiology after stapled gastroesophagostomy in dogs. AB - A stapled vertical gastroesophagostomy (VGE) has been proposed for benign esophageal stricture. The VGE involves performing an anastomosis using a linear cutting stapler inserted via a gastrotomy (one limb in the esophagus, the other in the proximal fundus). In phase I of the study, a 50-mm VGE was performed in 13 dogs; 7 received an additional fundoplication. Endoscopy with pinch biopsies, esophageal manometry, and 4-hour ambulatory pH recordings were performed in each dog prior to and 1 month after VGE. The only difference between groups postoperatively was a higher lower esophageal sphincter pressure in the group with the added fundoplication. The incidence of histologic esophagitis was low in both groups. In phase II of the study, a VGE was performed in six dogs using a 75 mm linear cutting stapler, accompanied by fundoplication in each dog. These dogs were then followed for 6 months to more completely assess the long-term risk of developing reflux esophagitis. At necropsy, no gross or histologic evidence of esophagitis was found. The performance of a VGE through the lower esophageal sphincter in normal dogs does not result in significant reflux esophagitis. VGE may be an alternative to resection for esophageal stricture. PMID- 1595838 TI - Elective treatment of bleeding varices with the Sugiura operation over 10 years. AB - A 10-year experience with the devascularization operation described by Sugiura is reported here. The operation was performed electively in 100 patients in whom it was not possible to place a shunt, all of whom had different kinds of hepatopathies (63 Child's A, 32 Child's B, and 5 Child's C). In 15 patients, the procedure was done in one stage (6% operative mortality, 1 patient), and, in 51, it was performed in two stages. Eight deaths were recorded in the 63 patients of the Child's A group, with a total of 111 operations. The operative mortality rate for this group was 12% and, as related to the number of operative procedures, 7% (8 of 111 operations). Seventeen patients were not considered for a second stage. Rebleeding in the early postoperative period was 4% and at long-term 6%. Incapacitating encephalopathy was found in 2 of the 71 surviving patients (3%). Survival (as determined by Kaplan-Meier tests) was 75% (1 year), 70% (5 years), and 69.2% (10 years). Six esophageal fistulas were observed secondary to transection. The Sugiura operation is an excellent complement to the therapeutic armamentarium used to treat portal hypertension, with low rebleeding and encephalopathy rates. PMID- 1595839 TI - Influence of spousal opinions on residency selection. AB - Fourth-year medical students face the difficult task of choosing a residency consistent with their career goals. Our study investigates the input of the spouse on the residency selection. From July 1, 1988, to July 1, 1990, questionnaires were sent to all 69 spouses of fourth-year medical students at the University of Arizona Medical Center. Fifty-six were returned for a response rate of 81%. Of the 16 women and 40 men who responded (mean age: 27 years), 55 (98%) spouse stated that there had been family discussions on the choice of a residency program, and 41 (73%) respondents thought that they had significant input. When asked to rank the items that most influenced their support for a particular training program, career goals of the medical student (68%) and lifestyle (21%) were most important, whereas prestige, earning capacity, and program length were ranked lowest. Specific concerns expressed by spouses on the selection of a surgical residency included time commitment as the most commonly cited (79%), followed by fatigue (48%). A statistically significant correlation existed between those spouses actively discouraging the choice of general surgery and those objecting to the time commitment during residency (p less than 0.05). We conclude that spouses have significant preferences regarding the choice of a training program following medical school. Career goals and lifestyle appear to be the most important factors; however, despite concern about the time commitment, the majority of spouses are supportive of the selection of a surgical residency. PMID- 1595840 TI - A predictive model for distant metastases in rectal cancer using DNA ploidy studies. PMID- 1595841 TI - Technique of hepatic vascular exclusion for extensive liver resection. AB - Hepatic vascular exclusion, which includes clamping of the portal pedicle along with the inferior vena cava below and above the liver, may be a useful procedure for resection of liver tumors close to the hepatic veins or the vena cava that are usually considered unresectable by conventional techniques. Since complete caval exclusion is the key to good hemodynamic tolerance and a bloodless transection of the liver parenchyma, several technical aspects of the procedure must be accomplished and are detailed. PMID- 1595842 TI - S-plasty for various anal lesions. AB - Ten patients underwent S-plasty between July 1979 and April 1990 for the treatment of various anal conditions. Six patients had giant condyloma acuminata, and there was one patient each with Bowen's disease, verrucous carcinoma, and stricture, and ectropion (Whitehead deformity). Both anatomic and functional results were satisfactory in all patients, and there were no serious complications. S-plasty is the preferred method for the reconstruction of extensive circular denuded anal canal with full-thickness graft of bilateral rotating skin flaps. It is important not only to construct large flaps with a good blood supply, but also to obtain complete hemostasis of the raw surface. PMID- 1595843 TI - Implications of sustained suppression of gastric acid secretion. AB - The implications of profound and sustained suppression of acid secretion are of increasing concern. Short-term inhibition of acid secretion by H2-receptor blockade or proton pump inhibition alters the gastric luminal flora and increases the risk of nosocomial pneumonia in critically ill patients who are receiving prophylaxis for stress gastritis. Long-term suppression alters gut flora, carcinogen levels in the gastric lumen, and the hormonal milieu, leading to proliferative changes in the fundic mucosa. Previous reports have noted a significant incidence of gastric malignancies in the achlorhydric environment of atrophic gastritis and pernicious anemia. Concern has also been expressed regarding the possibility of gastric neoplasia that arises after vagotomy and distal gastrectomy. The exact risk of gastric epithelial and endocrine hyperplasia or neoplasia in patients receiving potent antisecretory agents is not yet known, but such risks cannot be dismissed until long-term follow-up studies are available. The relationship between sustained suppression of acid secretion and the proliferation of epithelial and endocrine elements may provide insight into processes that regulate replication and growth of cells in the gastric mucosa. PMID- 1595844 TI - The intent of peer-reviewed journals. PMID- 1595845 TI - Prediction of difficult laryngoscopy: an assessment of the thyromental distance and Mallampati predictive tests. AB - Two hundred and fifty patients were assessed preoperatively using the Mallampati classification and by measuring their thyromental distances. The ease or difficulty of direct laryngoscopy was assessed at the time of induction of anaesthesia. Retrognathia was seen in 15.6% of patients and the incidence of difficult laryngoscopy without external laryngeal pressure was 8.2%. It was found that both assessments predicted less than two in three difficult laryngoscopies and had high false positive rates. It was found that external laryngeal pressure often improved the view of the glottis in difficult laryngoscopies. PMID- 1595846 TI - Persistence of allergy to anaesthetic drugs. AB - Intradermal testing and RIA testing for specific IgE antibodies to neuromuscular blocking drugs (NMBDs) were performed in patients referred to an Anaesthetic Allergy Clinic. Six patients were initially investigated four to 29 years after clinical anaphylaxis during anaesthesia and two of these patients and sixteen others were investigated by intradermal testing on two occasions at least four years apart. Seven patients had RIA tests for NMBD-specific IgE antibodies on two occasions at the time of skin testing. In all but two patients the evidence for drug-specific antibodies persisted 4-29 years after the reactions. In one patient all tests became negative and in another the skin test became negative but the positive RIA persisted. Evidence of antibodies to NMBDs persisted in 21 of 22 patients who had had anaphylactic reactions to these drugs during anaesthesia. In the absence of evidence of allergy diminishing with time in the majority of patients it would seem wise to avoid drugs responsible for reactions for the rest of the patient's life. PMID- 1595847 TI - The addition of pethidine to epidural bupivacaine in labour--effect of changing bupivacaine strength. AB - The effects of varying the strength of bupivacaine used in epidurals for the relief of labour pain was examined. The trial randomly allocated sixty women in the first stage of labour to one of three groups. All women were of ASA status 1 or 2 and had uncomplicated pregnancies. Subjects in each group received pethidine 25 mg in 10 ml of either 0.125%, 0.1875%, or 0.25% bupivacaine. Pain scores for each patient were then assessed over the following thirty minutes. Duration of analgesia and subsequent dose requirements were examined. No difference in pain scores between groups at thirty minutes after injection of the test solutions was found. The 0.25% solution group did however have a more rapid onset of analgesia with the majority of patients in this group achieving their maximum effect between ten and twenty minutes after injection. Duration of analgesia was not prolonged by using the stronger solutions. This study suggests that when epidural pethidine 25 mg is added to local anaesthetic solutions of bupivacaine, adequate analgesia for the first stage of labour is achieved with the 0.125% bupivacaine solution. The use of stronger solutions of bupivacaine achieves no greater degree of analgesia nor longer duration of action, although the onset of analgesia may be faster with the stronger solutions. Further investigations are needed to determine if 25 mg of pethidine is the best choice of dose to use under these circumstances. PMID- 1595848 TI - The relationship between a person's height and appropriate endotracheal tube length. AB - The relationship between a person's height and the dimensions of that person's upper airways has been studied in adult subjects. Using this relationship, formulae have been derived which predict appropriate lengths for endotracheal tubes. The formulae are as follows: 1. Orotracheal tube (teeth to mid-point of trachea) = Subject height (cm)/10 + 2 2. Orotracheal tube (teeth to mid-point of trachea + 3 cm) = Subject height (cm)/10 + 5 3. Nasotracheal tube (external naris to mid-point of trachea) = Subject height (cm)/10 + 8 These formulae are not foolproof but provide a useful working guide. All usual comfirmatory tests of correct placement should be employed. PMID- 1595850 TI - Propofol is a 'safe' anaesthetic agent in malignant hyperthermia susceptible patients. AB - In this study we investigated in vitro and in vivo effects of propofol in malignant hyperthermia susceptible (MHS) patients in order to assess the safety of propofol infusion as a non-triggering anaesthetic technique for diagnostic and therapeutic procedures. In vitro, human MHS muscle samples were exposed to propofol and changes in (a) baseline tension and (b) contracture tension on exposure to halothane and caffeine were measured. In vivo, (a) anaesthesia was induced in ten muscle biopsy positive MHS patients with propofol 2.5 mg/kg and (b) anaesthesia was produced in five muscle biopsy positive MHS patients with infusions of propofol up to 10 mg/kg/hr. In vitro, human MHS muscle did not develop contractures with propofol alone. Propofol had no significant effect on contracture development in response to halothane and caffeine. In vivo, no evidence of an MH response was detected following induction or maintenance of anaesthesia with propofol. Our results and literature review are in agreement that propofol is a 'safe' induction and maintenance agent in MHS patients. Propofol can be used for muscle biopsy anaesthesia because it does not alter the sensitivity of diagnostic muscle biopsy testing. PMID- 1595849 TI - Prevention of tachycardia with atenolol pretreatment for carotid endarterectomy under cervical plexus blockade. AB - A double-blind, randomised, controlled trial of forty patients was carried out to determine if oral atenolol pretreatment would reduce the incidence of tachycardia during carotid endarterectomy performed under cervical plexus block. Twenty patients received a placebo and twenty patients 50 mg of atenolol two hours prior to surgery. The superficial and deep cervical blocks were performed with 1.5% lignocaine containing 1:200,000 adrenaline. The patients were monitored with the V5 lead of the electrocardiogram and intra-arterial blood pressure. These measurements were recorded on a correctly calibrated paper recorder. Tachycardia (heart rate greater than 90 beats per minute for more than three minutes) occurred in thirteen patients in the placebo group and two patients in the atenolol group (P less than 0.01). There was no difference in the occurrence of bradycardia, hypotension or hypertension between the two groups. It is concluded that atenolol pretreatment is an effective method of reducing the incidence of tachycardia during carotid endarterectomy performed under cervical plexus blockade. PMID- 1595851 TI - Double-blind comparison of patient recovery after induction with propofol or thiopentone for day-case relaxant general anaesthesia. AB - Postoperative recovery after induction with either propofol or thiopentone has been compared in forty ASA I unpremedicated day surgery patients undergoing surgical extraction of third molar teeth under relaxant general anaesthesia. Mean recovery times in the propofol group, required for patients to sit out of bed (44.8 minutes; SD 18.6) and meet discharge criteria (113.1 minutes; SD 34.5) were significantly (P less than 0.05) shorter than those in the thiopentone group (59.7 minutes; SD 21.4 and 133.5 minutes; SD 34.5). Fewer patients in the propofol group were treated in the recovery room for nausea and vomiting and the incidence of mild nausea not requiring treatment was less in the propofol group, but these differences were not statistically significant. Postoperative mental performance, measured by the FAST index, a new test of mental speed, was reduced on average by 1.7% of preoperative levels, during the recovery period tested, with no significant difference between the groups. PMID- 1595852 TI - Flumazenil reversal of conscious sedation for minor oral surgery. AB - In order to find out whether resedation occurred following antagonism with flumazenil of sedation for minor oral surgery, in a double-blind randomised cross over study thirty healthy Hong Kong Chinese patients undergoing bilateral third molar surgery at two visits were sedated with midazolam. Following surgery they received either flumazenil or placebo at one visit and the alternative at the other visit. Recovery was monitored by observation and objective tests. Following recovery they were monitored for resedation for a total period of two hours from the injection of the reversal agent. Resedation, sufficient to prevent a patient from being discharged to be accompanied home with an escort, did not occur provided the patient responded to verbal command following sedation. PMID- 1595853 TI - Alveolar oxygenation and mouth-to-mask ventilation: effects of oxygen insufflation. AB - The effect on alveolar oxygen fraction (FAO2) of insufflating oxygen under a mask (or through an inflow nipple provided in the mask) during simulated mouth-to-mask ventilation was investigated using a lung model. A variety of commercially produced masks were evaluated. Two patterns of artificial ventilation were applied: 1. 500 ml tidal volume at 20 breaths per minute, and 2. 900 ml tidal volume at 12 breaths per minute. The ventilating gas mixture was oxygen 16% in nitrous oxide, and oxygen was insufflated at flow rates of 2, 4, 6, 8, 10, 12 or 14 litres per minute. The rate of rise of FAO2 and the equilibrium FAO2 attained were greatest at high oxygen inflow rates. The relationship between oxygen flow and FAO2 was not linear however, and an oxygen flow rate of 10 l/min was adequate to generate FAO2's around 50% with either ventilatory pattern. The equilibrium FAO2 achieved was greater with smaller tidal volumes and with larger mask deadspace. We also found that several breaths were required for equilibration of FAO2 during each trial, supporting recommendations that several breaths should be given on commencement of artificial ventilation during cardiopulmonary resuscitation. PMID- 1595854 TI - Effect of myocardial ischaemia-reperfusion on granulocyte elastase release. AB - During extracorporeal circulation, activation and degranulation of neutrophil granulocytes occur, with subsequent massive release of elastase, a neutral protease stored in the azurophil granules. Neutrophil granulocytes and oxygen derived free radicals are intimately involved in the occurrence of reperfusion injury, which affects especially the lungs and the myocardium. In this study we evaluated changes in the leucocyte count and of the plasma elastase levels in the coronary circulation during open heart surgery. We collected blood samples from the radial artery and the coronary sinus before skin incision, after onset of cardiopulmonary bypass and 5, 15, 30, 60, 120 minutes after the release of the aortic cross-clamp. The leucocyte count did not change significantly during the operation and no difference in leucocyte count was found between the radial artery and the coronary sinus. Plasma elastase levels significantly increased after the onset of cardiopulmonary bypass (P = 0.007) and after the release of the aortic cross-clamp (P = 0.001). Moreover, significantly higher values were found in the coronary sinus than in the radial artery 5 (P = 0.04), 15 (P = 0.02) and 30 (P = 0.02) minutes after the release of the aortic cross-clamp. We assume, therefore, that during the early phase of reperfusion, degranulation of neutrophil granulocytes occurs in the coronary circulation. PMID- 1595855 TI - The effects of oxytocin on the pulmonary and systemic circulation in pregnant ewes. AB - The haemodynamic effects of oxytocin on the pulmonary and systemic circulation were studied in six awake, pregnant (greater than 140 days gestation) ewes. Bolus doses of oxytocin 0.2 units/kg and then 0.8 units/kg were administered. A dose of 0.2 units/kg resulted in small but significant increases in mean pulmonary artery pressure (14%, P less than 0.05) and pulmonary vascular resistance (24%, P less than 0.05. A bolus of 0.8 units/kg resulted in a significant increase in mean arterial pressure (20%, P less than 0.05) and systemic vascular resistance (33%, P less than 0.05). Acute pulmonary hypertension was then induced with glass bead microemboli (150-200 microns), with an increase in pulmonary artery pressure of 26 mmHg and pulmonary vascular resistance of 448 dyn. s. cm-5. Boluses of oxytocin 0.2 and 0.8 units/kg were then administered. There were no significant changes, except for a 30% increase in systemic vascular resistance at one minute after oxytocin, 0.8 units/kg (P less than 0.05). PMID- 1595856 TI - A survey of Fellows of the Faculty of Anaesthetists of the Royal Australasian College of Surgeons endorsed in intensive care by examination in the first 10 years of final examinations in intensive care. AB - Fifty-nine of the 70 Fellows of the Faculty of Anaesthetists who had passed the Final Examination in Intensive Care including that of October 1989, responded to a questionnaire on the pattern of their intensive care and anaesthetic practice and their perception of the training and examination. Responses came predominantly from Fellows who had passed the examination more than two years previously. Forty-eight (81%) were practising intensive care at least 50% of the time and 51% had become Director or Deputy Director of an Intensive Care Unit. However, 51% maintained some anaesthetic practice. Although individuals had changed the intensive care/anaesthetic distribution of their practice, the group overall had not. With one exception all Fellows were practising in public hospitals but 26% in private hospitals also. Only eight had sought intensive care as their first vocational qualification. Training and examination were generally regarded favourably except for training in research methods and experience in internal medicine. The results suggest that the intensive care specialist is not likely to leave such practice in the long term, but there has been a reluctance to abandon altogether training and some subsequent practice in anaesthetics. PMID- 1595857 TI - Continuing Education Committee of Anaesthetists of New Zealand (CECANZ)--the first five years. PMID- 1595858 TI - Awake blind nasal intubation--a dying art? PMID- 1595859 TI - Difficult fibreoptic intubation in an intellectually handicapped patient. PMID- 1595860 TI - Superior vena cava syndrome following general anaesthesia. PMID- 1595861 TI - Co-existing peripheral and intracranial cavernous haemangiomas. PMID- 1595862 TI - Regional block and surgical outcome. PMID- 1595863 TI - Supraclavicular brachial plexus block. PMID- 1595864 TI - Convulsion after propofol/enflurane. PMID- 1595865 TI - Detection of faulty CO2 absorber by capnography. PMID- 1595866 TI - Confusing haemodynamic changes in intra-abdominal haemorrhage. PMID- 1595867 TI - Assisting fibreoptic intubation. PMID- 1595868 TI - Recertification. PMID- 1595869 TI - The end-tidal carbon dioxide detector for confirming tracheal intubation in animals. PMID- 1595870 TI - Water damage to capnography equipment. PMID- 1595871 TI - Decompression illness and nitrous oxide anaesthesia in a sports diver. PMID- 1595872 TI - Ferritin and venous cannula sepsis in TPN. PMID- 1595873 TI - Modification to base of anaesthetic machine. PMID- 1595874 TI - Suxamethonium in bunged cannulae. PMID- 1595875 TI - Bedside heparin monitoring. PMID- 1595876 TI - Oxygen connections to resuscitation equipment. PMID- 1595877 TI - Oximetry in cyanotic heart disease. PMID- 1595878 TI - Understanding pulse oximetry. PMID- 1595879 TI - Carbon monoxide poisoning. PMID- 1595880 TI - Does propofol have an anti-emetic effect? PMID- 1595881 TI - Anabolic steroids. PMID- 1595882 TI - Anaesthetic management for pancreatic stimulation test. PMID- 1595883 TI - Low molecular weight heparins (5 kDa) and oligoheparins (2 kDa) produced by gel permeation enrichment or radical process: comparison of structures and physicochemical and biological properties. AB - A process of chemical depolymerization of heparin initiated by free radicals has been developed. The process follows reaction kinetics of apparent first order, and it is possible to obtain heparins with different molecular weights. Low and very low molecular weight heparins (LMWHs, approximately 5 kDa, and Oligo-H, approximately 2 kDa) have been prepared by enriching fractions derived from natural heparin by gel permeation. The LMWHs produced by a radical reaction have been characterized by their physicochemical properties, patterns of constitutive disaccharides, NMR spectra, and biological activities in comparison with those of the LMWHs produced by an enrichment process. The process of free radical degradation is shown to produce heparins with a desired molecular weight (from 1 to greater than 10 kDa) without changes in their primary structure and in their physicochemical properties and with the in vitro biological activities expected for LMWHs. Furthermore, the limits of enzymatic cleavage of heparins with different molecular weights by heparinases and the possibility of obtaining a precise pattern of constitutive disaccharides are discussed. PMID- 1595884 TI - Affinity blotting assay for 2-5A-dependent RNase. AB - The intracellular effectors known as 2-5A (ppp-(A2'p)nA) regulate the cleavage of single-stranded RNA by activating a latent endoribonuclease (2-5A-dependent RNase or RNase L). Accordingly this enzyme may exist in either an inactive form, free of 2-5A, or an active, 2-5A-bound form. Previously, a radiobinding assay for 2-5A dependent RNase was developed that measured the amount of labeled ppp(A2'p)2A3' [32P]Cp, a derivative of ppp(A2'p)nA, that bound the inactive enzyme form. Because 2-5A-dependent RNase has a particularly high affinity for 2-5A the radiobinding assay may not measure the 2-5A activated form of the enzyme. Therefore an efficient procedure to facilitate the detection of total 2-5A dependent RNase (i.e., 2-5A-free and 2-5A-bound enzyme) in mouse spleen extracts was developed. Denaturing conditions were used to ensure that all 2-5A-dependent RNase was in the 2-5A-free form. After denaturation on polyacrylamide gel electrophoresis, optimal blotting conditions onto nitrocellulose and renaturation of the 2-5A binding site of 2-5A-dependent RNase were developed. This procedure allowed a population of enzyme that otherwise is not accessible by the classical radiobinding assay to be assayed, thus leading to an increased measurement of 15 17% in cytoplasmic spleen extracts. PMID- 1595885 TI - High sugar content of extracts interferes with colorimetric determination of amino acids and free proline. AB - Sugars were found to interfere with the determinations of alpha-amino nitrogen and free proline with ninhydrin. Suitable modifications are proposed for the quantitative analysis of these compounds in the presence of large amounts of carbohydrates. In this new method of proline assay, the improvement consists of using a citrate buffer adjusted to pH 4.6. Free proline is assayed by ninhydrin reagent prepared without phosphoric acid. This latter procedure uses less ninhydrin and appears to be simplified in comparison with the commonly used method. Both procedures permit a simple, sensitive, and specific determination of nitrogenous compounds in crude extracts. Elimination of carbohydrate interference makes our procedure applicable to crude extracts from various food products such as fruits and plants that accumulate soluble carbohydrates. PMID- 1595886 TI - Isolation and sequencing of CA/GT repeat microsatellites from chromosomal libraries without subcloning. AB - A method for the isolation of (CA)n microsatellites from chromosome-specific genomic libraries is described. Clones were first screened using a polynucleotide CA/GT probe. Those shown to contain CA repeats were plaque purified and either subcloned or the insert amplified directly using vector primers. Polymerase chain reaction products were then used to directly sequence the regions flanking CA repeats by using biotinylated primers that amplify cloned inserts outward from CA repeat containing regions of DNA to vector primers. This method provides rapid access to microsatellites from chromosomes or chromosome regions of interest. PMID- 1595887 TI - Isolation of secretory cells from plant glandular trichomes and their use in biosynthetic studies of monoterpenes and other gland products. AB - The natural products that accumulate in or exude from plant glandular trichomes are biosynthesized by secretory cells located at the apex of the trichome. To investigate the formation of glandular trichome constituents in several species of mints (Lamiaceae), a new procedure was developed for isolating large numbers of highly purified secretory cells. In this method, the leaf surface is gently abraded with glass beads in a way that fragments the glandular trichomes and yields clusters of intact secretory cells. The isolated, intact secretory cells and cell-free preparations derived from them are very active in monoterpene biosynthesis and provide useful starting materials for the purification of several key enzymes of monoterpene metabolism. The procedure described is adaptable to a broad range of plant species and should find wide application in the preparation of whole cell and cell-free systems for biosynthetic studies of plant natural products found in glandular trichomes. PMID- 1595888 TI - Construction and performance of a rapid scan monochromator for multiwavelength fluorimetry. AB - A rapid scan monochromator was constructed for multiwavelength illumination of biological samples. A light weight holographic grating (2400 grooves/mm) was driven by a rapid stepper motor with 0.014 degrees angular resolution in an f/4 monochromator. Angular velocity and acceleration kinetics were optimized to minimize the time for grating rotation and stabilization. The times required for shifting output wavelengths by 20, 100, and 300 nm were 6, 7, and 9 ms, respectively. Wavelength selection and dwell times were software controlled and reproducible over extended data collections. Instrument utility was demonstrated by measurement of intracellular calcium in fura-2-labeled Chinese hamster lung fibroblasts at excitation wavelengths of 340, 360, and 380 nm. Compared to available filter wheel and chopper devices, the rapid scan monochromator has advantages of rapid and software-selectable wavelength control, excellent optical alignment, small size, and low cost. Applications of this device include illumination optics for multiwavelength microfluorimetry and scanning absorption spectroscopy, and detection optics for microspectroscopy. PMID- 1595889 TI - Continuous assay of the hydrolytic activity of human immunodeficiency virus-1 protease. AB - A rapid sensitive method for the quantitation in vitro of HIV-1 protease activity has been developed. A fluorogenic compound, N alpha-benzoyl-Arg-Gly-Phe-Pro-MeO beta-naphthylamide, which contains Phe-Pro, a dipeptide bond recognized by HIV-1 protease, was used as substrate. The substrate was hydrolyzed by HIV-1 protease into a fluorescent naphthylated product (Pro-MeO-beta-naphthylamide). Fluorescence due to the release of Pro-MeO-beta-naphthylamide was measured continuously by spectrofluorometry. This oligopeptide was found to be a good substrate for HIV-1 protease. The Km and kappa cat for the hydrolysis of N alpha benzoyl-Arg-Gly-Phe-Pro-MeO-beta- naphthylamide by HIV-1 protease were calculated to be 2.0 +/- 0.2 mM and 75 +/- 6 s-1, respectively. These values are comparable with those of other natural substrates of HIV-1 protease. The method is highly sensitive, reproducible, and suited to a variety of applications, including the analysis of large numbers of samples for detailed enzymological studies. PMID- 1595890 TI - A method for characterization of endogenous ligands to orphan receptors belonging to the steroid hormone receptor superfamily--isolation of progesterone from pregnancy plasma using progesterone receptor ligand-binding domain. AB - An analytical method is described whereby progesterone is isolated from pregnancy plasma on the basis of the high affinity and specificity of the progesterone receptor for its ligand. Partially purified progesterone receptor ligand-binding domain, expressed as a protein A fusion protein in Escherichia coli, is incubated with a neutral steroid fraction obtained by extraction and ion-exchange chromatography of human late-pregnancy plasma. The incubated sample is passed through two Lipidex 1000 (lipophilic gel) beds. The first, at 4 degrees C, separates the specific ligand-fusion protein complex from nonspecifically bound and unbound compounds, and the second, at 40 degrees C, separates the specific ligand from the protein. Elution of the second bed with methanol yields a fraction containing specific ligand that can be characterized by gas chromatography-mass spectrometry. This methodology may be valuable for identification of endogenous ligands to orphan receptors of the steroid hormone receptor superfamily. PMID- 1595891 TI - The assessment of viability in isolated rat hepatocytes. AB - Isolated rat hepatocytes are used in many metabolic studies, but the viability of these cell preparations is often not adequately established. The present study shows that ATP content is a more reliable index of metabolic viability than trypan blue exclusion. At some of the low trypan blue exclusion levels quoted in the literature, a high percentage of cell preparations is likely to be nonviable by the criterion of ATP content. We suggest that ATP content measured on initial cell preparations and at the end of all incubation procedures is essential for establishing cell viability for metabolic studies on isolated hepatocytes. PMID- 1595892 TI - A semiautomated flow injection procedure for acetylcholinesterase and cholinesterase activities. AB - A stopped-flow FIA adaptation of the classical Ellman's colorimetric procedure for the measurement of acetylcholinesterase or cholinesterase activity is described. The samples are injected into a flow analytical system which is provided with an electronic timer and an electrovalve in order to stop the flow when the sample is inside the measurement cell. In this way, the absorbance-time relationship is obtained with a savings of sample, time, and reagents. PMID- 1595893 TI - A simple quantitative assay for chloramphenicol acetyltransferase by direct extraction of the labeled product into scintillation cocktail. AB - A simple, rapid, sensitive, quantitative, and inexpensive assay for chloramphenicol acetyltransferase (CAT) is described. The assay is based on the direct extraction of the products of the reaction into toluene-based liquid scintillation cocktail. The assay is carried out in 7-ml scintillation vials using 1 mM chloramphenicol and either 100 microM acetyl-CoA and 0.1 microCi of [3H]acetyl-CoA or 1 mM acetyl-CoA and 0.5 microCi of [3H]acetyl-CoA. After incubation, the reaction is terminated with 0.5 ml of 0.1 M sodium borate-5 M NaC, pH 9. The acetylchloramphenicols are extracted with 5 ml of 0.4% 2,5 diphenyloxazole-0.005% 1,4-bis(5-phenyloxazol-2-yl)benzene in toluene by a 30-s shaking. After a short centrifugation to clarify the layers, the vials are counted in a liquid scintillation counter. Extracted products are stable in the organic layer. Under these conditions, nearly 100% extraction of acetylchloramphenicols is shown using nonlabeled compounds and spectrophotometric methods. Using pure enzyme in the assay, linearity of activity with enzyme concentration, time, and temperature of incubation is demonstrated. Assays may even be carried out at 60 degrees C, where the enzyme activity is 3.4-fold higher than that at 23 degrees C. The increase in enzyme activity with increasing temperature is due to the increased formation of predominantly 3-acetyl and 1 acetylchloramphenicols and not to 1,3-diacetylchloramphenicol. The present assay compared very well with the standard assay using [14C]chloramphenicol and TLC. Using this assay, we measured quantitatively the CAT activity in extracts of pSV2 CAT-transfected CV-1 cells in 10 min and NIH 3T3 cell extracts in 60 min at 60 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595894 TI - Determination of organophosphorous and carbamate insecticides by flow injection analysis. AB - A flow injection system, incorporating an acetylcholinesterase (AChE) single bead string reactor (SBSR), for the determination of some organophosphorous (azinphos ethyl, azinphos-methyl, bromophos-methyl, dichlorovos, fenitrothion, malathion, paraoxon, parathion-ethyl and parathion-methyl) and carbamate insecticides (carbofuran and carbaryl) is presented. The detector is a simple pH electrode with a wall-jet entry. Variations in enzyme activity due to inhibition are measured from pH changes when the substrate (acetylcholine) is injected before and after the passage of the solution containing the insecticide. The percentage inhibition of enzyme activity is correlated to the insecticide concentration. Several parameters influencing the performance of the system are studied and discussed. The detection limits of the insecticides ranged from 0.5 to 275 ppb. The determination of these compounds was conducted in Hepes buffer and a synthetic sea water preparation. The enzyme reactor can be regenerated after inhibition with a dilute solution of 2-PAM and be reused for analysis. The immobilized enzyme did not lose any activity up to 12 weeks when stored at 4 degrees C. PMID- 1595895 TI - Direct dye binding--a quantitative assay for solid-phase immobilized protein. AB - A direct dye-binding procedure was established for the quantification of protein after its immobilization on a solid phase, using IgG and BSA as model proteins. The assay, which in the range 0-5 mg protein/ml gel correlates well with indirect protein determination by A280 as well as determination of protein hydrolyzed from the gel, is based on a modified Bradford dye-binding assay. As the protein coupled to the gel binds the dye, a decrease in A465 of the supernatant is measured. Three solid supports commonly used for protein immobilization (Sepharose, Sephadex, Sephacryl) were found to be compatible with the dye-binding assay while nonspecific dye binding was found to HEMA gels. Protein was coupled to Sephacryl S-1000 using three different activation methods (aldehyde, hydrazine, and adipic acid dihydrazide). Artifactual dye-binding was not observed using any of the three different "linkers." The assay is easily carried out and represents a useful tool, e.g., when optimizing procedures for protein immobilization. PMID- 1595896 TI - Phallotoxin and actin binding assay by fluorescence enhancement. AB - The fluorescence of five fluorophores conjugated to phallotoxins was found to be specifically enhanced upon binding to F-actin in a polymerizing buffer. Rhodamine phalloidin had the greatest fluorescence enhancement of ninefold. The fluorescence titration of rhodamine phalloidin by actin was shown to be consistent with stoichiometric binding. The fluorescence enhancement of rhodamine phalloidin at 5 microM is linearly related to F-actin concentrations up to 2 microM and therefore can be used as an easy means of F-actin quantitation. In a competition assay, other phallotoxins reduce the fluorescence enhancement that results from the binding of rhodamine phalloidin to polymerized actin. This reduction also permits a convenient measurement of the binding constants of any competing phallotoxins. PMID- 1595897 TI - A microassay for heme oxygenase activity using thin-layer chromatography. AB - A sensitive and facile assay for heme oxygenase (HO) has been developed. The basis of the assay is the detection of [14C]bilirubin formation in a coupled enzyme assay involving HO and biliverdin reductase actions, respectively. Separation of substrate from product is accomplished by thin-layer chromatography with subsequent quantitation by liquid scintillation counting of radioactive material present on chromatograms. As little as 20 micrograms of total cellular protein derived from cells growing in a standard 25-cm2 culture flask is sufficient for detection of HO enzyme activity using this assay. The reaction is inhibited by tin-protoporphyrin (10 microM final concentration), a specific inhibitor of HO. The linearity of the enzyme reaction with respect to incubation time and amount of protein used was established. Comparison of the new HO assay with a spectrophotometric assay was made, and good agreement of the results from both methods was found. The assay described here should facilitate measurements of this important heme-degrading enzyme in tissue culture studies and cases where limited amounts of material are available. PMID- 1595898 TI - Centrifugal elutriation of porcine oocytes isolated from the ovaries of newborn piglets. AB - A two step enzymatic procedure for the isolation of ovarian follicles and oocytes at early stages of development from the ovaries of newborn piglets was devised. The isolated oocytes were then separated from the overwhelming majority of the ovarian somatic cells using a centrifugal elutriation system. Twenty to thirty thousand oocytes were routinely collected after elutriation of the cell suspension derived from a pair of ovaries. In the enriched fraction the ratio of oocyte:somatic cells was between 1:1 and 1:3. The validation of the method as an efficient procedure for the isolation of a large, viable, and highly enriched population of oocytes at early stages of development was provided by uptake studies carried out after each step of the isolation and separation technique and by a comparative analysis of the pattern of structural proteins of the enriched fraction and of fully grown porcine oocytes. The results confirmed that the isolated cells were actually oocytes at early stages of development and that they were viable throughout the entire procedure. PMID- 1595899 TI - Radioreceptor assay of serum prolactin using nitrocellulose membrane-immobilized mammary prolactin receptor. AB - Triton-solubilized rabbit mammary prolactin (PRL) receptor was purified by concanavalin A-agarose chromatography and immobilized on a nitrocellulose membrane. Using the membrane-bound receptor and bovine serum, the serum level of PRL was determined by radioreceptor assay (RRA). The displacement curve, obtained by serial dilutions of the serum, was parallel to that obtained in the range of 0.4 and 20 ng/ml of standard bovine PRL. Serum could be included in concentrations up to 16% of the assay buffer and, thus, the detection limit of serum PRL was about 2.5 ng/ml. PRL in the serum was determined by radioimmunoassay (RIA). The ratio of the RIA and RRA estimates of PRL was 0.99 (r = +0.99, n = 55). The gel-filtration profile of serum PRL was identical to that obtained by RIA. It was concluded that membrane-bound receptor can be used for the determination of serum PRL. PMID- 1595900 TI - Electrofractionation: a technique for detecting and recovering biomolecules. AB - Electrofractionation (EF) is a technique that allows electrophoretic materials to be detected and recovered following electrophoresis. The EF apparatus utilizes the resolving power of electrophoresis and the mobile phase of liquid chromatography to create a continuous elution system. Our data indicate that EF is able to detect and recover oligonucleotides, as DNA fragments, proteins, and presumably other material that can be analyzed by electrophoresis. EF shares functional similarities with high-performance electrophoresis chromatography (HPEC) but operates by a different strategy and at a fraction of the cost. Moreover, EF can be constructed largely from standard laboratory equipment. The simplicity, rapid analysis times, low cost, and high recovery yields of EF make this system a practical alternative to the conventional detection and purification methods used for biomolecules. PMID- 1595902 TI - Mixtures of tight-binding enzyme inhibitors. Kinetic analysis by a recursive rate equation. AB - When two or more tight-binding inhibitors are present in an enzyme assay, the equation that relates the initial velocity v to the concentration of reactants cannot be written in an algebraically explicit form. Rather, for n inhibitors it is an implicit polynomial equation of degree n + 1 with respect to v. The complexity of the polynomial coefficients dramatically increases with each added inhibitor. Solving the transcendental rate equation by traditional methods of numerical mathematics has proven tedious because of the sensitivity of these methods to initial estimates and because of the existence of multiple roots. However, the equation can be rearranged into a convenient recursive form, one in which the velocity appears on both sides and the solution is found iteratively. The algebraic form of the recursive rate equation is remarkably simple and differs from the rate equation for classical rather than tight-binding inhibition only by an added term. The numerical stability and the speed of convergence were tested on the case of two competitive inhibitors. Initial estimates of velocity that spanned 12 orders of magnitude converged within five iterations. The velocities computed with the recursive method for a single tight-binding inhibitor were identical with the values predicted by the Morrison equation. The method is used to analyze experimental data for the inhibition of rat liver dihydrofolate reductase by mixtures of the anticancer drug methotrexate and its metabolic precursor form, methotrexate-alpha-aspartate (a prodrug). PMID- 1595901 TI - Peroxidase-amplified assay of sialidase activity toward gangliosides. AB - Sialidase assays were carried out with the substrate, ganglioside GD1a, coated onto enzyme immunoassay plate wells. Following the incubation of GD1a with sialidase from V. cholerae, the amount of ganglioside GM1 produced was measured as follows: cholera toxin B subunit conjugated to horseradish peroxidase was added to specifically bind to GM1, and then the amount of bound peroxidase was determined in a colorimetric enzymatic assay. In the absence of detergent, linearity for the detection of GM1 was 0 to 0.5 pmol per well, and the sensitivity for sialidase detection was about 3 fmol of product formed per minute. The addition of detergent (Triton CF-54) to the assay reduced the sensitivity and increased the amount of substrate required. Application of this assay for the detection of cell-derived neutral (pH 6.5) sialidase activities in the conditioned medium of human skin fibroblasts is described. PMID- 1595903 TI - Biomedical applications of analytical supercritical fluid separation techniques. PMID- 1595904 TI - Statistical determination of the average values of the extinction coefficients of tryptophan and tyrosine in native proteins. AB - Spectroscopic measurement of protein concentration requires knowledge of the value of the relevant extinction coefficient. If the amino acid composition of a protein is known, however, extinction coefficients can be calculated approximately, provided that the values of the molar absorptivities for tryptophan and tyrosine residues in the protein are known. We have applied a matrix linear regression procedure and a mapping of average absolute deviations between experimental and calculated values to find molar extinction coefficients (epsilon M, 1 cm, 280 nm) of 5540 M-1 cm-1 for tryptophan and 1480 M-1 cm-1 for tyrosine residues in an "average" protein, as defined by a set of experimentally determined extinction coefficients for more than 30 proteins. Use of these values provides a significant improvement in extinction coefficient estimation over that obtained with the commonly used values obtained from solutions of model compounds in guanidine-HCl. The consistency of these results when compared to the large deviations often observed between experimentally determined extinction coefficients suggest that this method may offer acceptable accuracy in the initial estimation of molar absorptivities of globular proteins. PMID- 1595905 TI - Site-directed mutagenesis of virtually any plasmid by eliminating a unique site. AB - We describe an efficient site-specific mutagenesis procedure that is effective with virtually any plasmid, requiring only that the target plasmid carry a unique, nonessential restriction site. The procedure employs two mutagenic oligonucleotide primers. One primer contains the desired mutation and the second contains a mutation in any unique, nonessential restriction site. The two primers are annealed to circular single-stranded DNA (produced by heating circular double stranded DNA) and direct synthesis of a new second strand containing both primers. The resulting DNA is transformed into a mismatch repair defective (mut S) Escherichia coli strain, which increases the probability that the two mutations will cosegregate during the first round of DNA replication. Transformants are selected en masse in liquid medium containing an appropriate antibiotic and plasmid DNA is prepared, treated with the enzyme that recognizes the unique, nonessential restriction site, and retransformed into an appropriate host. Linearized parental molecules transform bacteria inefficiently. Plasmids with mutations in the unique restriction site are resistant to digestion, remain circular, and transform bacteria efficiently. By linking a selectable mutation in a unique restriction site to a nonselectable mutation, the latter can be recovered at frequencies of about 80%. Since most plasmids share common vector sequences, few primers, targeted to shared restriction sites, are needed for mutagenizing virtually any plasmid. The procedure employs simple procedures, common materials, and it can be performed in as little as 2 days. PMID- 1595906 TI - A method for the direct measurement of mRNA in discrete regions of mammalian brain. AB - A rapid and nearly quantitative method for the direct analysis of steady-state mRNA levels in microgram quantities of frozen mammalian brain is described. Briefly, tissue punches 0.5-1.0 mm in diameter were sampled from 250-microns thick cryostat sections of rat brain (approximately 50-200 micrograms tissue). The samples were homogenized in 50 microliters of a denaturing gel loading buffer and applied directly to a 2.2 M formaldehyde-agarose gel for electrophoresis and subsequent RNA blot analysis. The method is extremely rapid, results in excellent recovery of intact RNA, and allows the direct assay of mRNA levels in discrete subregions of the mammalian brain. PMID- 1595907 TI - Posttraumatic respiratory insufficiency: how and why does it happen? PMID- 1595908 TI - Noninvasive cardiac output measurement: troubled technologies and troubled studies. PMID- 1595909 TI - Assessment of changes in lung microvascular permeability in posttraumatic acute lung failure after direct and indirect injuries to lungs. AB - We prospectively studied the variation in sequence of occurrence of lung microvascular permeability (LMVP) increase and clinical onset of posttraumatic acute lung failure (ALF) in the sequential failure of organ systems after direct and indirect lung injury. Acute lung failure developed in 52 of 255 trauma patients. Thirty-seven of these developed ALF after a direct injury to lung tissue and 11 after an indirect injury. Lung microvascular permeability was measured with a gamma camera simultaneously over both lungs using indium 113m labeled transferrin and technetium 99m-labeled erythrocytes in 24 patients with ALF due to direct lung injury and in 4 with ALF due to indirect injury. A localized increased LMVP was observed initially only in the directly traumatized lung (traumatized/nontraumatized lung: 10.03 +/- 5.08/3.73 +/- 3.33 %/h), but involved the primarily nontraumatized lung within 4 days (traumatized/nontraumatized lung: 9.13 +/- 4.49/10.89 +/- 5.05 %/h). In contrast, in ALF due to indirect lung injury, an increased LMVP over both lungs was observed initially (right/left lung: 11.57 +/- 6.18/12.63 +/- 5.73 %/h) and 4 days later (right/left lung: 12.3 +/- 5.49/11.92 +/- 5.75 %/h). Acute lung failure due to direct lung injury occurred significantly earlier (less than 72 h) (P less than 0.01), whereas onset of indirectly induced ALF was later (greater than 72 h). Sepsis syndrome and multiple organ failure were the major complications once ALF occurred after a direct injury. In contrast, sepsis syndrome and multiple organ failure commonly preceded or paralleled the onset of ALF due to an indirect injury.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595910 TI - Clinical evaluation of transtracheal Doppler for continuous cardiac output estimation. AB - A newly developed transtracheal Doppler (TTD) computer for cardiac output determination was studied in nine patients after open heart surgery (coronary artery bypass grafting, n = 4; mitral valve replacement, n = 5). The measurements were compared with those simultaneously obtained by thermodilation. Doppler signals were adequate in 78% of the patients studied. Limited correlation between both methods (r = 0.248; r2 = 0.0615; mean of difference, 1.714 +/- 1.67 L/min; limits of agreement, -1.6 to 5.0 L/min) was found. The large difference in cardiac output readings between TTD and thermodilation may be due to (a) false angles of the ultrasound beam in relation to the aortic wall and blood flow or (b) misplacement of the ultrasound head and underestimation of the aortic lumen. Patients must be completely sedated and paralyzed to prohibit artifacts. Routine patient care can interfere with continuous measurements. Cardiac output determinations by TTD are limited to the period during which the trachea is intubated with the special TTD tube. We conclude that the TTD system does not offer accurate cardiac output determinations and that the routine use of this device is not practical. PMID- 1595911 TI - Hemodynamic effects of anesthesia in patients chronically treated with angiotensin-converting enzyme inhibitors. AB - Angiotensin-converting enzyme inhibitors (ACEIs) are increasingly used in the treatment of cardiovascular disease, but recent reports have warned of some hemodynamic risk (hypotension and bradycardia) when associated with anesthesia. To assess the hemodynamic effects of induction of anesthesia in patients chronically treated with ACEIs, 16 hypertensive patients scheduled for coronary artery bypass graft surgery (n = 12) or vascular surgery (n = 4) were studied. Eight of them were chronically treated (for at least 1 mo) with ACEIs (ACEI group), and the remaining eight (control group) were treated with other classes of antihypertensive drugs. Induction of anesthesia, which consisted of flunitrazepam (0.03 mg/kg), fentanyl (0.006 mg/kg), and pancuronium (0.1 mg/kg) IV, was followed by a significant decrease in mean arterial blood pressure from baseline in both groups (by 16.8% in controls [P = 0.001] and 33.5% in ACEI treated patients [P = 0.001] [P = 0.041 between groups]). In control patients, mean arterial blood pressure decrease was only associated with a significant decrease in cardiac index (-18%, P = 0.014). In ACEI-treated patients, the arterial blood pressure decreases were associated with consistent reductions in pulmonary capillary wedge pressure (-26.4%; P = 0.035) and cardiac index (-23.9%; P = 0.001). Systemic vascular resistance index and heart rate were moderately changed (-14.2% and -4.5%, respectively). Rapid restoration of arterial blood pressure was obtained in all ACEI-treated patients, mainly with the intravenous administration of 0.4 to 0.7 L of lactated Ringer's solution. Phenylephrine (0.38 +/- 0.9 mg) was, however, required in four patients when mean arterial blood pressure was less than 60 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595912 TI - Intravenous nifedipine to treat hypertension after coronary artery revascularization surgery. A comparison with sodium nitroprusside. AB - We administered sodium nitroprusside (SNP) or nifedipine intravenously to patients who became hypertensive after elective coronary revascularization and compared their effects on hemodynamics and the electrocardiogram in a parallel, randomized, open-label study. Four of 21 patients treated with nifedipine required the addition of SNP to maintain mean arterial pressure less than 90 mm Hg, compared with 4 of 28 patients in the SNP group who required the addition of nifedipine. The success rates of nifedipine (81%) and SNP (86%) were not significantly different. There was no difference in the incidence of adverse ST segment changes during drug infusion (4% versus 5%) or perioperative myocardial infarction (9.5% versus 10.7%) in the nifedipine versus SNP groups, respectively. The plasma nifedipine concentration (mean value +/- SD) at steady state for 21 patients receiving nifedipine was 119 +/- 42.5 ng/mL. The pharmacokinetic variables for nifedipine were as follows (mean values +/- SD): systemic clearance, 0.525 +/- 0.228 L.h-1.kg-1; apparent volume of distribution, 0.738 +/- 0.446 L/kg; and elimination half-life, 1.02 +/- 0.51 h. These values are similar to those reported previously in healthy volunteers. We conclude that intravenous nifedipine can be used safely to control hypertension after coronary revascularization but were unable to demonstrate an advantage of nifedipine compared with SNP in preventing postoperative ischemia or infarction in this group of patients who had good left ventricular function. PMID- 1595913 TI - Intravenous regional bretylium and lidocaine for treatment of reflex sympathetic dystrophy: a randomized, double-blind study. AB - Patients with reflex sympathetic dystrophy, who received transient pain relief from stellate ganglion blocks or lumbar sympathetic blocks and had abnormal isolated cold stress tests, were enrolled in a study to determine the efficacy of intravenous regional bretylium. Each patient received two control treatments (0.5% lidocaine) and two treatments with 0.5% lidocaine and bretylium 1.5 mg/kg in a randomized, double-blind fashion. A standard intravenous regional technique was used with a 300-mm Hg tourniquet pressure for 20 min. Patients kept a daily record of pain relief (0 = no relief, 100% = complete relief). A decrease in pain of more than 30% was considered clinically significant. Therefore, once the patient's pain relief was less than 30%, the next intravenous regional treatment was performed. Bretylium and lidocaine provided more than 30% pain relief for a mean of 20.0 (+/- 17.5) days, whereas lidocaine alone provided relief for only 2.7 (+/- 3.7) days (Mann-Whitney U-test, P less than 0.001). A mean temperature increase in the treated limb of +2.64 +/- 3.41 degrees C above the baseline temperature was noted after bretylium administration, whereas after control treatments the change was -0.086 +/- 1.30 degrees C (Mann-Whitney U-test, P less than 0.02). We conclude that the combination of bretylium and lidocaine is significantly more effective than lidocaine alone when an intravenous block is used to treat reflex sympathetic dystrophy. PMID- 1595914 TI - Analgesic effect of intraarticular bupivacaine or morphine after arthroscopic knee surgery: a randomized, prospective, double-blind study. AB - The effect of 20 mL of intraarticular bupivacaine (0.25%, with or without 1:200,000 epinephrine), morphine (0.03%, with or without 1:200,000 epinephrine), or normal saline on postoperative analgesia after arthroscopic knee surgery was studied in a randomized, prospective, double-blind trial in ASA I-III outpatients receiving general anesthesia (n = 112) or regional anesthesia (n = 27 [spinal (n = 25) or epidural (n = 2)]). The visual analogue pain scores in the postanesthesia care unit and 3, 6, 12, and 24 h after surgery, time to first analgesic use, and total 24-h analgesic requirements were recorded. In those who received general anesthesia, the visual analogue scores were significantly lower in the bupivacaine group compared with both the morphine- and placebo-treated patients (P less than 0.05). The time to first analgesic use was longer in both the bupivacaine and morphine groups when compared with the control group (P less than 0.05). No significant differences were detected in total 24-h analgesic requirements among the groups. Patients who had received regional anesthesia had lower visual analogue scores compared with patients who had received general anesthesia irrespective of the intraarticular treatment (P less than 0.05). Our results indicate that intraarticular injection of bupivacaine after arthroscopic knee surgery provides prolonged analgesia but that there is no significant prolonged analgesia provided by intraarticular morphine. PMID- 1595915 TI - Prolongation of canine epidural anesthesia by liposome encapsulation of lidocaine. AB - The purpose of our study was to produce a long-acting lidocaine by using a liposome that would entrap the drug. Egg yolk phosphatidylcholine and cholesterol were used as liposome materials. After epidural administration, the pharmacodynamics and pharmacokinetics of liposomal and free lidocaine were studied in 20 dogs. Two percent liposomal or free lidocaine (3.0 mL) was injected into the lumbar epidural space. Nerve blocking effects were estimated by measuring somatosensory evoked potentials. Recovery time from the epidural block in the liposomal lidocaine group (170 +/- 49.5 min) was approximately three times longer than that in the free lidocaine group (61 +/- 18.1 min). The areas under the drug concentration-time curves (AUC0-infinity) and time to maximal concentration (Tmax) in the liposomal lidocaine group were significantly larger than those in the free lidocaine group. These results suggest that the prolongation of epidural blockade by liposomal lidocaine is caused by a slow release of the drug from liposomes. The present study suggests that liposomal lidocaine can be used as a long-acting local anesthetic. PMID- 1595916 TI - Effects of epidural and spinal anesthesia on blood rheology. AB - This study was designed to compare the influence of epidural and spinal anesthesia on blood viscosity. We studied 22 patients, ASA classification I, who underwent elective knee or ankle arthroscopy and received epidural (n = 11) or spinal (n = 11) anesthesia with plain bupivacaine, and 10 control volunteers, who did not undergo surgery or receive anesthesia. There were significant decreases in hematocrit, plasma viscosity, and whole-blood viscosity at high (70 s-1), medium (0.5 s-1), and low (0.05 s-1) shear rates. The magnitude of changes was similar in all groups but occurred earlier in the control group (between 10 and 30 min) and after spinal administration (between 10 and 30 min) rather than after epidural administration (between 30 and 60 min) of bupivacaine. Only spinal anesthesia was associated with a decrease in erythrocyte deformability. The observed rheologic changes are attributed to hemodilution from the intravenous administration of fluids and the redistribution of fluid in the intravascular and extravascular compartments after sympathetic blockade and to postural changes rather than the effect of bupivacaine on blood elements. PMID- 1595917 TI - Nimodipine reduces the toxicity of intravenous bupivacaine in rats. AB - We examined nimodipine modification of bupivacaine toxicity in anesthetized male rats. Three minutes after pretreatment, group 1 (n = 11), group 3 (n = 10), and their respective control groups (n = 11 and n = 9) received intravenous bupivacaine LD50 (median lethal dose). After pretreatment, group 2 (n = 10), group 4 (n = 8), and their respective control groups (n = 10 and n = 8) received intravenous bupivacaine LD90 (90% lethal dose). Pretreatment was 200 micrograms/kg intravenous nimodipine in groups 1 and 2 and 500 micrograms/kg in groups 3 and 4. Control animals were pretreated with intravenous saline solution. Data were analyzed by chi 2-analysis and analysis of variance. Survival increased after 200 micrograms/kg nimodipine (P less than 0.05). In group 1, 9 (81%) of 11 survived compared with control animals (4 [36%] of 11). In group 2, 8 (80%) of 10 survived compared with control animals (2 [20%] of 10). Survival was not increased after 500-micrograms/kg nimodipine pretreatment. In group 3, 2 (22%) of 9 survived compared with control animals (4 [40%] of 10). In group 4, 4 (50%) of 8 survived compared with control animals (2 [25%] of 8). We conclude that nimodipine pretreatment with 200 micrograms/kg protects against fatal toxicity from LD50 and LD90 bupivacaine, but 500 micrograms/kg does not. PMID- 1595918 TI - Segmental analgesic effect and reduction of halothane MAC from epidural fentanyl in humans. AB - To clarify the site of action of epidural fentanyl, we compared the effects of epidural and intravenous fentanyl on the change in pressure pain threshold (PPT) and the minimum alveolar concentration (MAC) of halothane. Seventy patients who underwent gastrectomy in the PPT study group and 84 female patients who underwent hysterectomy in the MAC study group were assigned randomly to seven groups in each study. The seven groups each received a bolus injection of 1, 2, or 4 micrograms/kg of fentanyl, either intravenously or epidurally, and of saline solution epidurally. Compared with intravenous fentanyl, epidural fentanyl significantly increased (P less than 0.01) PPT around surgical incisions by approximately 50%, 100%, and 150% of preadministration levels 1 h after administration of 1, 2, and 4 micrograms/kg, respectively, and significantly reduced (P less than 0.05) halothane MAC at the same doses. These data suggest that the more potent analgesic and anesthetic effects of epidural fentanyl, compared with intravenous fentanyl, are due mainly to the segmental analgesia produced by its spinal analgesic action. PMID- 1595919 TI - Phenylephrine does not limit myocardial blood flow or oxygen delivery during isoflurane-induced hypotension in dogs. AB - Experiments were performed on seven fentanyl-pentobarbital-anesthetized, open chest dogs to determine whether stimulation of coronary alpha 1-adrenergic receptors by phenylephrine causes coronary vasoconstriction and impaired myocardial oxygen delivery when phenylephrine is infused to correct isoflurane induced hypotension. Myocardial blood flow was measured with radioactive microspheres, and myocardial oxygen and lactate extraction were determined. The Fick equation was used to calculate myocardial oxygen consumption. Measurements were obtained (a) under control conditions, (b) after a 30-min inhalation of isoflurane sufficient to decrease mean aortic pressure by 30%, and (c) while maintaining administration of isoflurane, 5-10 min after restoration of mean aortic pressure by intravenous infusion of phenylephrine. Isoflurane-induced hypotension was accompanied by a baroreceptor-mediated increase in heart rate and by a decrease in myocardial oxygen consumption; however, myocardial blood flow was maintained, resulting in decreased oxygen extraction and increased coronary sinus PO2, thus implying a direct coronary vasodilating effect for isoflurane. Lactate extraction was unaffected. Phenylephrine infusion during inhalation of isoflurane returned mean aortic pressure and heart rate to their respective control values, and it did not change myocardial oxygen consumption, myocardial blood flow, myocardial oxygen extraction, coronary sinus PO2, or lactate extraction from values obtained during isoflurane alone. These latter findings are consistent with undiminished coronary vasodilation by isoflurane in the presence of phenylephrine. In conclusion, infused phenylephrine to restore aortic pressure during isoflurane administration had no vasoconstrictor effect in the coronary circulation and did not impair myocardial oxygen delivery. Apparently, the direct coronary vasodilating action of isoflurane completely nullified phenylephrine-induced vasoconstriction via local alpha 1-adrenergic receptors. PMID- 1595920 TI - Venodilation contributes to propofol-mediated hypotension in humans. AB - The present investigation explored the possibility that the commonly observed hypotension that occurs during induction of anesthesia with propofol might be related to its ability to produce venodilation. Thirty-six ASA I and II patients who received no premedication were studied. The first 20 patients were divided into two equal groups. Hemodynamic measurements consisted of heart rate, arterial blood pressure, and forearm venous compliance by occlusive plethysmography. Baseline measurements were made in awake patients while resting in a supine position. Repeat measurements were made during steady-state infusions of propofol (2.5 mg/kg bolus injection, followed by a continuous infusion at 200 micrograms.kg-1.min-1) or thiopental (4 mg/kg bolus injection, followed by continuous infusion at 200 micrograms.kg-1.min-1), 10 min after tracheal intubation while patients were artificially ventilated. Both anesthetics resulted in a significant (P less than 0.05) and similar tachycardia; however, propofol produced significant decreases in systolic (-30 +/- 9 mm Hg) and diastolic (-11 +/- 4 mm Hg) arterial blood pressure. Forearm venous compliance was significantly increased during propofol administration but unchanged in patients receiving thiopental. In four additional patients receiving smaller consecutive infusions of propofol (50 and 100 micrograms.kg-1.min-1), significant subtle increases in forearm compliance were also recorded. These increases were not observed in four patients who received placebo infusions. Thus, one mechanism promoting hypotension during propofol anesthesia in humans seems to be related to its direct effects on venous smooth muscle tone and presumably venous return. PMID- 1595921 TI - Sore throat after endotracheal intubation. AB - Nitrous oxide can diffuse into the cuff of an endotracheal tube during tracheal intubation, and the cuff pressure against the tracheal wall may cause mucosal damage. An endotracheal tube has been developed (Brandt Anesthesia Tube) that effectively limits nitrous oxide-related intracuff pressure increases. We determined whether the incidence of postoperative sore throat could be reduced by using this tube. Forty-eight female patients, 18-50 yr of age, were included in the study. Endotracheal intubation was performed with either a Brandt Anesthesia Tube or a Mallinckrodt endotracheal tube. All patients were interviewed postoperatively after 20-30 h by individuals who did not know which tube was used. In the Mallinckrodt group, 12 of 20 patients had a sore throat and 10 patients had intracuff pressures greater than 25 mm Hg. Only 3 of 20 patients in the Brandt group had a sore throat. We found that the incidence of sore throats after intubation could be significantly reduced by using the Brandt Anesthesia Tube (P less than 0.005). PMID- 1595922 TI - Do-not-resuscitate in the operating room: moral obligations of anesthesiologists. PMID- 1595923 TI - An updated cross-referenced filing system for anesthesiologists. AB - A filing system that provides a medical-information retrieval system is useful for medical students, physicians-in-training, and practicing physicians. The present system is an expansion and update of the one proposed by Petty and Carden in 1973. This filing system for anesthesiologists contains a simple numerical index of the major categories in the anesthetic, medical, and surgical literatures. The organ system and the anesthetic considerations are combined. A cross-reference index is provided as well. This system allows the user to cross file reprints, locate ones that have been loaned, and keep track of references that may be found in personal bound volumes. The files may be expanded over the years to any desired degree. Finally, this system may be of use either to the individual anesthesiologist or to a department's library. PMID- 1595924 TI - pH of stomach contents. PMID- 1595925 TI - pH of stomach contents. PMID- 1595926 TI - Another use for precordial stethoscopes. PMID- 1595927 TI - Digital nerve blocks and pulse oximeter signal detection. PMID- 1595928 TI - Stomal leaks and gas bubbles. PMID- 1595929 TI - How to dislodge a severely trapped epidural catheter. PMID- 1595931 TI - An inexpensive and practical cable holder. PMID- 1595930 TI - Chronic headache resulting from postoperative supraorbital neuralgia. PMID- 1595932 TI - Predictive values of cervical spine radiographs in trauma patients. PMID- 1595933 TI - Is there a role for the Finapres when arterial lines are used? PMID- 1595934 TI - A complication with a pulmonary artery catheter. PMID- 1595935 TI - Are resterilized 29-gauge spinal needles clean? PMID- 1595936 TI - Use of the buccal route for the administration of an antiemetic. PMID- 1595937 TI - Rate of injection of propofol for induction of anesthesia. PMID- 1595938 TI - Jacoby's line rather than Tuffier's line as a guide to lumbar puncture. PMID- 1595939 TI - Cardiosynchronous limb compression: effects on noninvasive vascular tests and clinical course of the ischemic limb. AB - Some patients with chronic arterial obstruction of the limbs may still suffer the consequences of advanced tissue ischemia, including ulceration and rest pain, and face threatened limb loss in spite of available surgical, pharmacologic, and other treatments. Additional therapeutic modalities were thus sought to accomplish limb salvage. A literature review indicated that most reports on R wave-triggered circumferential limb compression (cardiosynchronous limb compression [CSC]) demonstrate its ability to augment limb arterial blood flow and improve ischemic limbs. To determine the device's efficacy and safety, and possibly confirm earlier positive reports, a systematic study was undertaken, using older, as well as newer, more electronically reliable CSC devices. The present study was designed to determine the following: 1. objectively, by noninvasive vascular tests, changes in limb blood flow, if any, by CSC; 2. clinical effects of CSC, if any, on the ischemic limb; 3. duration of CSC-induced limb improvements, if any; 4. side effects or safety of CSC. The study demonstrated that CSC treatments: 1. caused increased limb blood flow as determined by increased ankle/arm indices and hallux photoplethysmograph waveform amplitudes during treatments; 2. led, in most cases, to improvement in or resolution of the presenting ischemic problem (eg, ulcer, cellulitis, rest pain); 3. induced limb improvements that persist for up to seven years 4. caused no adverse side effects. PMID- 1595940 TI - Vasodilator action of pentoxifylline on microcirculation of rat cremaster muscle. AB - Pentoxifylline improves microvascular blood flow in conditions of vascular insufficiency. The clinical benefits of pentoxifylline have been attributed to its effects on the cellular elements of whole blood, although a few studies suggest it may also be a vasodilator. The purpose of this study was to determine whether pentoxifylline has a vasodilator effect on the luminal diameter of small arteries preconstricted with norepinephrine and on resting small arteries in the rat cremaster muscle. Intravital videomicroscopy was used in order to observe directly the vasodilator capacity of topically applied pentoxifylline. The results reveal that pentoxifylline (100 microM and more) can significantly dilate small arteries preconstricted with norepinephrine. Pentoxifylline had no effect on the diameter of resting small arteries. These results suggest that vasodilation may play a role in the ability of pentoxifylline to improve arterial blood flow. PMID- 1595941 TI - First-pass radionuclide cineangiography: a reevaluation of its sensitivity and limitations in the detection of significant coronary artery disease. AB - The sensitivity of first-pass cineangiography in the detection of significant coronary artery disease (CAD) was recently assessed in 33 patients. No normal controls were studied. Overall sensitivity was 86% with a predictive value of 83% and a 36% false-positive rate. Attainment of an adequate exercise end point increased sensitivity to 92%; failure to achieve this end point diminished sensitivity to 71%. Correlation between first-pass and contrast angiography ejection fractions was high (r = 0.88, p less than .005) with a moderate correlation in wall motion analysis (r = 0.58, p less than .005). The development or the intensification of a wall motion abnormality (WMA) was the single most sensitive indicator of CAD (84%). Presence of WMA plus failure of the ejection fraction to increase by 6% over baseline increased testing sensitivity to 89%. The mean WMA score for patients with CAD was 2.0 +/- 1.5 compared with 0.6 +/- 1.3 for those with normal study results (p less than .01). The first-pass method identified 4 subjects who subsequently had normal findings from catheterization. Data confirm testing sensitivity of the first-pass technique and underscore the apparent limitations of this modality in differentiation of patients with normal vasculature. PMID- 1595942 TI - Is sublingual nifedipine administration superior to oral administration in the active treatment of hypertension? AB - Nifedipine, a calcium-channel-blocking agent, was administered orally to 44 untreated patients (Group A) and sublingually to 51 untreated patients (Group B) who had a diastolic blood pressure more than 90 mm Hg and systolic blood pressure more than 140 mm Hg. The mean pretreatment systolic and diastolic blood pressure values were 185.3 +/- 26.0 and 115.1 +/- 13.4 mm Hg in Group A patients and 193.6 +/- 23.1 and 118.1 +/- 14.1 mm Hg in Group B patients respectively (p greater than 0.05). The hypotensive activity of nifedipine was observed at the tenth minute in both groups. Mean systolic and diastolic pressures were 168.9 +/- 23.7 and 101.9 +/- 14.2 mm Hg in Group A and 170.6 +/- 26.2 and 103.0 +/- 15.8 mm Hg in Group B, (p less than 0.001) Diastolic blood pressures dropped under 100 mm Hg at the twentieth minute in both groups. Maximal reduction of blood pressure was observed at the fortieth minute in both groups and the degree of reduction in blood pressure was also the same (mean systolic and diastolic blood pressures: 143.7 +/- 22.1 and 86.9 +/- 11.7 in Group A and 148.7 +/- 21.4 and 91.7 +/- 17.0 in Group B (p less than 0.05). The authors conclude that sublingual nifedipine administration is not superior to oral nifedipine administration (in capsular form) in the acute treatment of hypertension. PMID- 1595943 TI - Skin flow the venoarteriolar response and capillary filtration in diabetics. A 3 year follow-up. AB - Resting skin blood flow (RF) and the venoarteriolar response (VAR = the vasoconstrictor response on standing) have been studied in 100 patients with diabetic neuropathy, in 100 diabetics without neuropathy, and in 100 normal subjects by laser Doppler flowmetry. Capillary filtration was also studied with strain gauge plethysmography. The authors followed up these patients by evaluating their microcirculation again after three years. At the beginning of the study in patients with neuropathy, RF and capillary filtration were increased. The VAR and the microangiopathy index (MI = VAR/RF) were reduced in all diabetics, to a greater extent to those with neuropathy. After three years the authors observed an increase in capillary filtration associated with a further impairment in VAR and MI, suggesting progression of microangiopathy in both groups of diabetics. These results suggest that the postural control of blood flow in the skin of the foot is impaired in diabetic microangiopathy, particularly in neuropathics. Increased skin blood flow and capillary filtration and the impaired venoarteriolar response cause edema and may contribute to the thickening of capillary basement membranes and the progressive evolution of diabetic microangiopathy. PMID- 1595944 TI - Successful dissolution of massive left atrial thrombus after the use of warfarin- a case report. AB - A case of rheumatic heart disease, mitral stenosis, large left atrium, and chronic atrial fibrillation is reported and discussed. This patient was shown, by means of two-dimensional echocardiography, to have a massive left atrial thrombus, and after the initiation of anticoagulation with warfarin, complete resolution of the clot was seen in less than two months. The use of two dimensional echocardiography was valuable in the follow-up of this patient, and it is suggested that further prospective studies are necessary for better understanding the natural history of left atrial thrombus. PMID- 1595945 TI - Anomalous septal perforator artery: a source for supportive circulation in severe coronary artery disease--case reports. AB - Anomalous origin of a septal perforator artery is an infrequent angiographic finding. However, its recognition is important in patients with coronary artery disease in order to avoid misdiagnosis and consequent management mistake. In 2 patients, coronary arteriography demonstrated an anomalous septal perforator artery supplying significant blood flow to a myocardial region previously perfused by a severely obstructed major coronary vessel. It appears that an anomalous septal artery can serve as an important source for supportive circulation in severe coronary artery disease. PMID- 1595946 TI - Hemodynamic characteristics of patients with coronary artery disease presenting false-negative exercise stress test. AB - The present study was designed to clarify the characteristics of left ventricular hemodynamics and coronary arteries in patients with coronary artery disease presenting false-negative response to the Master's two-step stress test. Eighty eight consecutive patients performed the Master's two-step stress test and had coronary angiography for evaluation of suspected or known coronary artery disease. The frequency of false-negative and true-positive responses in the Master's two-step stress test was 20% and 45%, respectively. Elevated left ventricular end-diastolic pressure, reduced ejection fraction, and low cardiac output characterized the left ventricular hemodynamics in patients with false negative responses, as compared with those with true-positive response. The severity and extent of coronary artery disease, as well as prior myocardial infarction, did not affect the frequency of false-negative response. This study indicates that the false-negative response to the Master's two-step test is unexpectedly frequent in coronary artery disease with severe left ventricular dysfunction. Thus, one should be careful in judging the results of the Master's two-step test in symptomatic patients with severe left ventricular dysfunction. PMID- 1595947 TI - Neoplastic phlebothrombosis from renal vein to right atrium: a case report. AB - The authors present an atypical case of neoplastic thrombosis of the great abdominal veins, evaluated with echo-Doppler duplex scanner and computed tomographic scan with contrast enhancement. In this report the authors stress again the diagnostic accuracy of echo-Doppler methods in the study of such a phlebopathy. They describe its sonographic differential diagnosis from acute or chronic idiopathic phlebothrombosis. PMID- 1595948 TI - Diagnosis of pulmonary arteriovenous malformation by ultrafast chest computed tomography in Rendu-Osler-Weber syndrome with cerebral ischemia--a case report. AB - Pulmonary arteriovenous malformations occur in 15-20% of patients with Rendu Osler-Weber syndrome and can be the source of paradoxical emboli causing cerebral ischemia, septic emboli leading to brain abscesses, or polycythemia causing hyperviscosity and cerebral ischemia. The diagnosis of these malformations may be elusive, since classic clinical or radiologic findings may be absent in some patients. The authors report a patient with Rendu-Osler-Weber syndrome with cerebral ischemia who had normal findings from a pulmonary examination and chest roentgenogram. An ultrafast computed tomography scan of the chest demonstrated, however, a pulmonary arteriovenous malformation in the right upper lobe that was successfully resected. Ultrafast computed tomography of the chest is a relatively noninvasive method of screening for a pulmonary arteriovenous malformation in a patient with Rendu-Osler-Weber syndrome and otherwise unexplained neurologic symptoms. PMID- 1595949 TI - Total pulmonary torsion without vascular compromise--a case report. AB - A new case of pulmonary torsion is reported. Only 15 cases of this rare entity have been published in the literature, all of them either surgically treated short term or resulting in death. Small right-side pneumothorax following diagnostic transthoracic puncture seemed to be the mechanism of production. Because of the absence of acute clinical manifestations, fibroscopy, isotopic perfusion scanning, and hemodynamic and pulmonary angiographic studies were done. The lack of compromise in the pulmonary flow and venous pulmonary return explains the surprisingly good progress (ten months, at present) of the patient. PMID- 1595950 TI - Effects of ischemia on left ventricular contractility. PMID- 1595952 TI - Histologic features of the carotid artery trifurcation in thoroughbreds. AB - The common, external, and internal carotid and occipital arteries were examined histologically at the trifurcation of the common carotid arteries in 13 Thoroughbred foals (0 to 30 days old) and 64 Thoroughbred adults (2 to 4 years old). Calcification in the media of the common carotid and external carotid arteries was observed in 3 of the 13 foals and in 30 of the 64 adult horses. Calcification resembled that seen in Monckeberg's arteriosclerosis in human beings, the cause of which is unknown. PMID- 1595951 TI - An experimental model for subclinical edema disease (Escherichia coli enterotoxemia) manifest as vascular necrosis in pigs. AB - An experimental model for subclinical edema disease was developed in weanling pigs. In multiple experiments, 3-week-old pigs were weaned, then inoculated intragastrically with 10(10) colony-forming units of an SLT-IIv-positive strain of Escherichia coli originally isolated from a pig with edema disease (principals). Control pigs were inoculated with a nonpathogenic E coli strain. Of 39 principals, 8 developed clinical edema disease within 14 days after inoculation. However, 20 of 21 principals that did not develop clinical signs of edema disease, but were submitted for necropsy examination at 14 days after inoculation, had characteristic vascular lesions of edema disease. Vascular lesions, found principally in ileum and brain, consisted of segmental necrosis of myocytes in the tunica media of small arteries and arterioles. None of the pigs inoculated with a nonpathogenic strain of E coli developed edema disease or vascular lesions. None of the principals necropsied at 2 days after inoculation had vascular lesions. Development of vascular lesions by 14 days after inoculation was used as the end point for detecting subclinical edema disease in the model. PMID- 1595953 TI - Effect of short-term exposure of chickens to corticosterone on resistance to challenge exposure with Escherichia coli and antibody response to sheep erythrocytes. AB - Chickens in a low-stress environment (heterophil/lymphocyte ratio 0.31) were given feed containing 30, 40, or 60 mg of corticosterone/kg of feed for 0.5 hour. Between 0.5 to 12 hours later, chickens were exposed to Escherichia coli via the air sac route. For each dose of corticosterone, there was an untreated control group that was exposed to E coli via the air sac route. The prevalence of pericarditis was reduced from 78 to 7% between 2 and 4 hours after exposure. Resistance was associated with heterophil/lymphocyte (H/L) ratios greater than 1.04. Peak H/L ratios correlated positively with amount of corticosterone in the feed. In one experiment, chickens were inoculated IV with sheep erythrocytes at various times after consumption of feed containing corticosterone. Suppression of antibody responsiveness was most pronounced 4 hours later. Antibody responsiveness correlated positively with lymphocyte numbers. Histologic examination of air sacs was made following euthanasia at various times after E coli exposure. Lesions observed in control chickens included: edema at 0.5 hour, beginning of heterophil infiltration at 1 hour, increased edema and heterophil infiltration at 2 hours, and severe edema and heterophil infiltration at 4 hours. Lesions were not observed in chickens that had been given feed containing 40 mg of corticosterone/kg of feed. PMID- 1595954 TI - Investigation of renal protein loss in dogs with acute experimentally induced Ehrlichia canis infection. AB - Urinary protein-to-creatinine ratios and serum albumin concentrations were measured in 8 adult male dogs experimentally inoculated with Ehrlichia canis. Urinary protein concentration increased significantly, but transiently, during the acute phase of infection. Urinary protein-to-creatinine ratios were highest (mean, 8.6) during the third and fourth weeks after infection, and decreased to less than 0.5 by 6 weeks after infection. Correspondingly, albumin concentration decreased significantly during the acute phase. Serum albumin concentrations were lowest (mean, 2.1 g/dl) the fourth week after infection and increased to greater than 3.0 g/dl by 11 weeks after infection. There was an inverse linear correlation between urinary protein-to-creatinine ratio and serum albumin concentration. The magnitude of proteinuria and its inverse relationship with serum albumin concentration suggested that hypoalbuminemia associated with acute E canis infection may be attributable primarily to increased renal loss of protein, rather than decreased hepatic synthesis as previously suggested. Another dog was subsequently inoculated with E canis from 1 of the experimentally infected dogs and a renal biopsy was performed during peak proteinuria (urinary protein-to-creatinine ratio = 22 and serum albumin = 1.1 g/dl). Immunofluorescent staining revealed mild to moderate deposits of anti-canine IgM, and to a lesser extent, anti-canine IgG and complement factor C3 in the glomerular tufts and mesangium. Ultrastructural evaluation revealed distortion and fusion of podocyte foot processes and increased microvilli on podocytes. These morphologic changes were consistent with transient glomerular leakage of protein of a magnitude that would significantly contribute to hypoalbuminemia during acute E canis infection. An underlying immunologic mechanism was suggested by positive glomerular immunofluorescence and previously described histologic findings. PMID- 1595955 TI - Use of computerized interactive morphometry in the diagnosis of mammary adenoma and adenocarcinoma in dogs. AB - We attempted to define quantitative objective criteria for diagnosis of mammary adenoma and adenocarcinoma in dogs. To that end, correlation between diagnosis made by conventional histologic examination and morphometric descriptors, obtained by computerized histologic analysis, was assessed in biopsy specimens of mammary tissue from 63 dogs. We used 2 interactive computer procedures: one assessed mean nuclear perimeter, mean nuclear area, and circularity factor; and the other evaluated nuclear stratification and cell crowding. A data base was generated with 11 specimens from normal mammary tissue, 17 specimens from mammary adenoma, 18 specimens from low-grade mammary adenocarcinoma, and 15 specimens from mammary adenocarcinoma. The mean values of nuclear perimeter, nuclear area, nuclei per millimeter of basement membrane, and minimal distances from cells to basement membrane gradually increased from normal to high-grade malignancy. Distributions of nuclear areas and of minimal distances from cells to basement membrane were shifted in specimens from malignant tumors. Multivariate analysis confirmed the homogeneity of the diagnostic groups. PMID- 1595956 TI - Effect of intravenous and aerosol administration of 5-hydroxytryptamine on pulmonary function values in healthy calves. AB - Effects of IV and aerosol administration of 5-hydroxytryptamine (5-HT) on ventilation, pulmonary mechanics values, pulmonary arterial pressure, and heart rate were investigated in healthy unsedated Friesian calves. Minute volume increased significantly, mainly because of an increase in respiratory rate. Except for total pulmonary resistance after bolus injection, continuous administration of 5-HT given by either route caused significant alterations of lung dynamic compliance and total pulmonary resistance, the former decreasing to one-fifth of its baseline value and the latter increasing twofold. Pulmonary arterial pressure increased significantly, whatever the speed or route of administration. Administration of a bolus did not affect heart rate, whereas continuous IV administration of 5-HT as well by perfusion or by aerosol resulted in sustained tachycardia. It was concluded that 5-HT induces reversible bronchoconstriction and pulmonary vasoconstriction in healthy unsedated calves, 5 HT-induced functional alterations depend on the speed of administration, and excess of 5-HT production or depression in uptake by the lungs during bovine respiratory tract diseases could contribute to pulmonary dysfunction. PMID- 1595958 TI - Amino acid profiles in dogs with chronic renal failure fed two diets. AB - Amino acid profiles and serum albumin and serum total protein concentrations were evaluated in dogs with renal disease. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF; exogenous creatinine clearance, 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal control dogs were fed a diet containing 31% protein for 8 weeks, at which time serum and urine amino acid assays and clearance studies were performed. All dogs then were fed a diet containing 16% protein for 8 weeks and then reevaluated. Chronic renal failure was associated with mild abnormalities in serum concentrations of amino acids. When fed the higher protein diet, dogs with CRF had lower serum concentrations of glutamine, leucine, proline, and serine and higher serum concentrations of cystathionine and 3 methylhistidine than clinically normal control dogs. When fed the low protein diet, dogs with CRF had lower serum serine concentrations and higher serum concentrations of cystathionine, phenylalanine, and 3-methylhistidine. Urine excretion of amino acids in all dogs on both diets was low, and dogs with CRF had lower renal clearances of 3-methylhistidine than control dogs. There were no significant differences in concentrations of serum albumin and total solids between either group, regardless of diet. We concluded that dogs with mild to moderately severe CRF have mild abnormalities of serum free amino acid concentrations, but renal conservation of essential amino acids is not impaired. PMID- 1595957 TI - Clinical and metabolic findings in dogs with chronic renal failure fed two diets. AB - Exogenous creatinine clearance, urinary electrolyte excretions, calcium and phosphorus balance, serum cholesterol concentration, arterial blood pressure, and body weight were evaluated in dogs with chronic renal failure that were fed 2 commercial diets. Nine dogs ranging in age from 1 to 15 years were identified as having mild to moderate chronic renal failure (CRF, exogenous creatinine clearance = 0.5 to 2.13 ml/kg of body weight/min). These dogs and a group of 10 clinically normal controls were fed a diet containing 31% protein for 8 weeks at which time hematologic and biochemical evaluations and clearance studies were performed. All dogs then were fed a phosphorus-restricted diet containing 16% protein and then reevaluated after 8 weeks. The dogs in this study had hematologic and biochemical abnormalities typical of CRF. Urine absolute and fractional excretion of electrolytes was higher in dogs with CRF than in controls and was affected by diet. Serum cholesterol concentration was higher in dogs with CRF and increased in those dogs after feeding the low protein diet. Changes in dietary sodium intake did not affect arterial blood pressure. The phosphorus restricted diet did not affect serum amino terminal parathyroid hormone concentration in either group. Control dogs lost body weight, whereas dogs with CRF gained weight when fed the low protein diet. We concluded that dogs with mild to moderately severe CRF have the same biochemical abnormalities and response to dietary restriction of protein and phosphorus as has been previously reported in dogs with experimentally induced CRF. Restriction of dietary sodium may not decrease arterial blood pressure in some dogs with CRF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595959 TI - Ultrasonographic appearance of the uterus, placenta, fetus, and fetal membranes throughout accurately timed pregnancy in beagles. AB - Serial ultrasonographic examinations were performed on 8 Beagle bitches from 20 to 60 days pregnant to determine time of first detection, appearance, and sizes of selected features of pregnancy. Gestation was timed from the day of the preovulatory luteinizing hormone surge. Findings related to gestational age were consistent among bitches. Gestational ages at earliest detection of the following features were: chorionic cavity at day 20; placental layers in the uterine wall at day 22 to 24; zonary placenta at day 27 to 30; embryo and heartbeat at day 23 to 25; yolk sac membrane at day 25 to 28; allantoic membrane at day 27 to 31; choroid plexus of the brain at day 31 to 35; fetal movement at day 34 to 36; skeleton at day 33 to 39; bladder and stomach at day 35 to 39; kidney at day 39 to 47; and liver hypoechoic, compared with lung, at day 38 to 42. Extra-fetal structures were measurable from day 20 or 22 through day 48. Chorionic cavity diameter increased from 0.2 +/- 0.0 cm to 3.3 +/- 0.2 cm, outer uterine diameter increased from 0.8 +/- 0.03 cm to 4.8 +/- 0.2 cm, length of chorionic cavity or zonary placenta increased from 0.3 +/- 0.03 cm to 4.9 +/- 0.05 cm, uterine wall thickness increased from 0.3 +/- 0.03 cm to 0.8 +/- 0.01 cm, and placental thickness increased from 0.1 +/- 0.0 cm to 0.5 +/- 0.05 cm. Chorionic cavity diameter, outer uterine diameter, and placental length each increased at a linear rate through day 37, after which time, each had a marked plateau in growth. Of the extra-fetal structures, chorionic cavity diameter was the most accurate for estimation of gestational age. All of the fetal structures studied increased at an increasing (second order) rate. Crown-rump length increased from 0.3 +/- 0.05 cm on day 24 to 9.2 +/- 0.2 cm on day 48. Body diameter increased from 0.2 +/- 0.03 cm on day 24 to 4.6 +/- 0.15 cm on day 60. Head diameter increased from 0.8 +/- 0.05 cm on day 34 to 2.7 +/- 0.04 cm on day 60. Of the fetal structures, head diameter was the most accurate for estimation of gestational age. PMID- 1595960 TI - Comparison of two catheter withdrawal speeds during simultaneous urethral pressure profilometry in anesthetized bitches. AB - Maximal urethral closure pressure, functional profile length, and number of respiratory peaks on the resting urethral pressure profile, expressed as a percentage of those occurring on the bladder pressure recording, were compared at catheter withdrawal speeds of 1 and 3 mm/s in 30 anesthetized bitches. Significant (P less than 0.001) differences were found in maximal urethral closure pressure and percentage of transmission of respiratory peaks between the 2 speeds. Significant difference was not detected in functional profile length. PMID- 1595961 TI - Interaction of bovine chorioallantoic membrane explants with three strains of Brucella abortus. AB - Chorioallantoic membrane (CAM) explants were used to determine the in vitro growth and cytotoxic potential of 3 strains of Brucella abortus. Bovine CAM explants were inoculated with 2 x 10(7) colony-forming units of the pathogenic strain 2308, attenuated strain 19, or the rough strain RB51 of B abortus. After inoculation, the explants were harvested and examined at 2 or 4 hours, 12 or 14 hours, and 24 or 26 hours of incubation. Bacterial growth associated with each explant was determined by counting colony-forming units. The degree of cellular damage in each explant associated either with bacterial growth or bacterial toxins was evaluated by morphometric analysis after trypan blue staining. Significant differences were not detected in the numbers of bacteria of any strain of B abortus in the CAM explants at comparable time intervals. The rate of growth of the bacteria in CAM explants was higher between 2 and 12 hours after inoculation than between 12 and 24 hours after inoculation. Cytotoxic effects associated with strain 2308 were significantly (P less than 0.05) greater than that caused by other strains. Cytotoxic effects associated with strain 19 and rough strain RB51 were similar, and both were significantly (P less than 0.05) greater than the phosphate buffer solution control. Chorioallantoic membrane explants inoculated with a filtrate of heat-killed strain 2308 induced minimal cellular damage, compared with that caused by the viable bacteria. These results indicated that the number of B abortus in trophoblasts was independent of the degree of cellular damage. PMID- 1595962 TI - Epidemiologic investigation of a silage-associated epizootic of ovine listeric encephalitis, using a new Listeria-selective enumeration medium and phage typing. AB - The role of silage feeding in the origin of an epizootic of encephalitic listeriosis in a sheep flock was investigated by use of a new direct Listeria selective isolation and enumeration medium, in combination with serotyping and phage typing. The silage contained high numbers (about 10(6) cells/g) of a L monocytogenes strain indistinguishable with respect to serovar and phagovar from that isolated from the brains of sick sheep. These results provided unambiguous bacteriologic evidence of the epidemiologic link between silage consumption and listeriosis in ruminants. PMID- 1595963 TI - Effect of probenecid on the pharmacokinetics of flunixin meglumine and phenylbutazone in healthy mares. AB - Pharmacokinetic values for flunixin meglumine (1 mg/kg of body weight) and phenylbutazone (4 mg/kg) dosages were determined after a single IV injection with and without concurrent intragastric administration of probenecid (50 mg/kg) in 6 healthy mares. Significant difference was not apparent in the pharmacokinetic values of flunixin meglumine with and without concurrent probenecid administration. Significant (P less than or equal to 0.05) increase was evident in the 12-hour mean concentration of phenylbutazone (11.45 +/- 1.66 micrograms/ml without probenecid; 14.56 +/- 1.20 micrograms/ml with probenecid) along with significant (P less than or equal to 0.05) reduction in its volume of distribution at steady state associated with concurrent probenecid administration (218.6 +/- 11.52 ml/kg without probenecid; 169.4 +/- 9.25 ml/kg with probenecid). PMID- 1595964 TI - Intramammary administration of gentamicin as treatment for experimentally induced Escherichia coli mastitis in cows. AB - In 8 Holstein cows, 50 colony-forming units (CFU) of Escherichia coli was administered into 1 mammary gland. Infections were established in all inoculated glands. In 4 of the 8 cows, 500 mg of gentamicin sulfate was administered by intramammary infusion 14 hours after inoculation; the other 4 cows were untreated controls. Infusions of gentamicin also were given after each of the 3 successive milkings after the initial infusion, so that a total dose of 2 g of gentamicin was given to each of the treated cows. During the 33-hour treatment period and for the first milking after the last infusion of gentamicin, the treated cows had a mean gentamicin concentration of greater than or equal to 31.0 micrograms/ml in milk samples that were collected from inoculated quarters immediately before each milking. Concentrations of 0.34 and 0.69 micrograms of gentamicin/ml were detected in milk from 2 cows at 8 days after inoculation with E coli. Mean serum concentrations of gentamicin were greater than or equal to 0.37 micrograms/ml throughout the treatment period and the first 12 hours after the last infusion, with a mean peak concentration of 0.96 micrograms/ml at 24.4 hours. The range of peak concentration of gentamicin detected in urine from all treated cows was 42 to 74.4 micrograms/ml. Peak concentration of E coli in milk in the treated cows (6.08 +/- 1.02 log10 CFU/ml) did not significantly (P greater than 0.05) differ from that of the control cows (5.26 +/- 1.00 log10 CFU/ml). Similarly, mean duration of infection in the treated cows (54 hours) did not differ significantly from that of the control cows (48 hours).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595966 TI - Evaluation of polysaccharide, lipopolysaccharide, and beta-glucan antigens in gel immunodiffusion tests for brucellosis in cattle. AB - In Venezuela, 1,012 cattle sera were screened for their ability to precipitate Brucella melitensis 16M smooth-lipopolysaccharide (S-LPS), B melitensis B115 polysaccharide B (poly B), B abortus 1119-3 O-polysaccharide (PS), or B abortus 1119-3 cyclic 1,2 linked beta-D-glucan (beta-glucan) in an agar-gel immunodiffusion assay. These sera were previously classified as being Brucella abortus-infected, S-19-vaccinated, or negative after an assessment of historical records and results of 5 standard serologic tests. Most of the sera (85%) from infected cattle precipitated S-LPS, poly B, and PS. Serologic results for poly B and PS were identical. On the other hand, 13% of the sera from vaccinated cattle precipitated S-LPS, but none of these sera precipitated poly B or PS. It was concluded that purified PS can alternate with poly B as an antigen to differentiate sera of B abortus-infected from B abortus S-19-vaccinated cattle. None of these sera precipitated beta-glucan. PMID- 1595965 TI - Indocyanine green disposition in healthy dogs and dogs with mild, moderate, or severe dimethylnitrosamine-induced hepatic disease. AB - Disposition kinetics of indocyanine green (ICG) were used to evaluate hepatic function in healthy Beagles (group 1; n = 6) and Beagles with progressive hepatic disease induced by oral administration of dimethylnitrosamine, a hepatospecific toxin. Three classes of hepatic disease were defined by histologic features: mild (group 2; n = 5), moderate (group 3; n = 6), and severe (group 4; n = 5). Disposition of ICG was studied 3 weeks following the last dose of toxin. A rapid IV injection of 0.5 mg of ICG/kg was administered and serum samples were obtained at certain intervals during 60-minute periods. Serum ICG was analyzed by use of visible spectrophotometry. Disposition kinetics were determined from serum ICG concentrations vs 15- and 60-minute time curves and compared between one another and among groups. Data based on 60-minute time curves were not significantly different from those based on 15-minute curves. Area under the curve for ICG was greatest in group 3. Clearance of ICG was decreased and mean resident time was increased in groups 3 and 4, compared with those in groups 1 and 2. When disposition data (60 minutes) were normalized for differences in hepatic weight among dogs, group-3 mean resident time was significantly greater than that of group 4. This study supports the diagnostic benefits of using ICG disposition kinetics as a method of evaluating hepatic function in dogs with progressive liver disease. PMID- 1595967 TI - Measurement of lymphoblast proliferative capacity of stimulated blood mononuclear cells from cattle with chronic paratuberculosis. AB - Concanavalin A (conA) blast proliferation as a quantitative measure of lymphoblast proliferative capacity by blood mononuclear cell supernatants was measured in cattle naturally infected with Mycobacterium paratuberculosis and in healthy control cattle. Blast cell proliferation was significantly reduced in infected animals, compared with control cattle when blood mononuclear cells were stimulated with conA. Proliferation was significantly greater than media control when M bovis purified protein derivative and johnin were used to stimulate cells from the infected group. After sensitizing control and affected cattle with M paratuberculosis bacterin (live M bovis and keyhole limpet hemocyanin in Freund's incomplete adjuvant), infected animals had no difference in blast cell proliferative capacity with the mycobacterial antigens and conA stimulation, whereas healthy animals had significantly increased blast proliferation in response to all the sensitizing antigens. The blast cell proliferative capacity in infected animals with keyhole limpet hemocyanin stimulation was increased significantly after sensitization; however, it remained significantly less than that in the sensitized control group. These data indicate that cattle naturally infected with M paratuberculosis probably produce suboptimal interleukin-2 (IL-2) activity in response to a potent IL-2 inducer (conA) and fail to optimize IL-2 activity when sensitized with a potent immunogen (keyhole limpet hemocyanin). PMID- 1595968 TI - Cerebrospinal fluid changes after iopamidol and metrizamide myelography in clinically normal dogs. AB - Cerebrospinal fluid samples from 2 groups of clinically normal dogs were compared after iopamidol (n = 9) and metrizamide (n = 8) myelography. Iopamidol (200 mg of I/ml) and metrizamide (170 mg of I/ml) were administered by cerebellomedullary injection at dosage of 0.45 ml/kg of body weight. In dogs of both groups, postmyelographic CSF changes included high specific gravity, Pandy score, protein concentration, and WBC count. The high specific gravity and Pandy score were false-positive effects attributed to nonionic contrast media. Although postmyelographic protein concentration and total WBC count were greater in CSF samples from dogs given metrizamide than in those given iopamidol, differences were not statistically significant. The differential WBC counts were consistent with mild, acute leptomeningitis; these findings were supported by results of histologic examination. Iopamidol and metrizamide should be considered low-grade leptomeningeal irritants in dogs. PMID- 1595970 TI - Guideline issued for urinary incontinence. PMID- 1595969 TI - Dimethylnitrosamine-induced hepatotoxicosis in dogs as a model of progressive canine hepatic disease. AB - A model of toxin-induced progressive hepatitis is described in Beagles. The toxin, dimethylnitrosamine, was administered orally to 18 Beagles; 6 dogs comprised a control group. Clinical signs and laboratory test results were monitored as disease progressed and were used to determine the end point of disease. Following euthanasia, histologic lesions were scored and used to derive a total severity score for each dog. Severity scores were then used to allot the 18 dogs to 3 groups of hepatic disease, defined as mild, moderate, or severe. Changes in clinical laboratory test results, including tests of hepatic function, and clinical signs indicative of liver disease were described chronologically for all dogs. Group means of clinical laboratory test results and quantifiable clinical signs (eg, weight loss and ascitic fluid accumulation) were compared. This model offers several advantages, compared with other experimental models of canine hepatic disease. These include hepatospecificity, similarity to natural disease (eg, the development of multiple extrahepatic portosystemic shunts), and the ability to titrate the disease to a desired end point. The major disadvantages of this model were the toxic nature of the drug to human beings and the variation in individual animal response to the toxin, which precludes preassignment of animals into groups. PMID- 1595971 TI - ANA opposes Bush gag rule memo. PMID- 1595972 TI - A day in the life of a nurse: cardiac transplant nurse assists patient, family in dynamic process. PMID- 1595973 TI - Board develops tactics to move nursing's agenda. PMID- 1595974 TI - Nurses provide care in many settings. PMID- 1595975 TI - Attitude is vital to advancement. PMID- 1595976 TI - Change and growth in Midwest. PMID- 1595977 TI - Our diversity gives us strength. PMID- 1595978 TI - Skill mix change may be a trap. As I see it. PMID- 1595979 TI - TB--it can threaten your future. PMID- 1595980 TI - Home at last. PMID- 1595981 TI - ANA to revise nursing statement. PMID- 1595982 TI - Mental disorder and violent behavior. Perceptions and evidence. PMID- 1595983 TI - The science of choosing the right decision threshold in high-stakes diagnostics. AB - Many diagnostic tasks require that a threshold be set to convert evidence that is a matter of degree into a positive or negative decision. Although techniques of decision analysis used in psychology help one select the particular threshold that is appropriate to a given situation and purpose, just the concept of adjusting the threshold to the situation is not appreciated in many important practical arenas. Testing for the human immunodeficiency virus (HIV) and for dangerous flaws in aircraft structures are used here as illustrations. This article briefly reviews the relevant techniques and develops those two examples with data. It suggests that use of the decision techniques could substantially benefit individuals and society and asks how that use might be facilitated. PMID- 1595984 TI - Understanding implicit memory. A cognitive neuroscience approach. AB - Dissociations between implicit and explicit memory have attracted considerable attention in recent memory research. A central issue concerns whether such dissociations require the postulation of separate memory systems or are best understood in terms of different processes operating within a single system. This article presents a cognitive neuroscience approach to implicit memory in general and the systems-processes debate in particular, which draws on evidence from research with brain-damaged patients, neuroimaging techniques, and nonhuman primates. The article illustrates how a cognitive neuroscience orientation can help to supply a basis for postulating memory systems, can provide useful constraints for processing views, and can encourage the use of research strategies that the author refers to as cross-domain hypothesis testing and cross domain hypothesis generation, respectively. The cognitive neuroscience orientation suggests a complementary role for multiple systems and processing approaches. PMID- 1595985 TI - Giving advice. Decision theory perspectives on sexual assault. AB - What entitles us to give general advice? This general question is explored here in the specific context of providing responsible advice to women on how to make decisions about possible ways of reducing their risk of sexual assault. An approach is advanced that is a combination of decision analysis, used to provide a formal characterization of decision situations, and behavioral decision theory, used to provide a descriptive characterization of how people perceive those situations. The approach is illustrated with a set of studies using three diverse groups of women; a group of men, paralleling one of the groups of women; and a national sample of sexual assault experts. The approach is evaluated in terms of its feasibility, its strengths and weaknesses relative to alternative approaches, and its implicit position on broader political and philosophical issues. PMID- 1595986 TI - Airway hyperresponsiveness and airway wall thickening in asthma. A quantitative approach. PMID- 1595987 TI - A model of airway narrowing in asthma and in chronic obstructive pulmonary disease. AB - We have examined the effect of airway wall thickening, loss of lung recoil, and airway smooth muscle shortening on the increase in airway resistance using a model of the human tracheobronchial tree. The values for airway wall thickening were determined morphometrically on the postmortem or surgically resected lungs of normal subjects, patients with moderate chronic obstructive pulmonary disease, and patients with severe asthma. Loss of recoil was simulated by deflating airways along their pressure-area curves by 1 to 3 cm H2O. Values of smooth muscle shortening between 20 and 40% were used in the model to generate sigmoidal shaped "dose-response" curves. The analysis shows that moderate amounts of airway wall thickening, which have little effect on baseline resistance, can profoundly affect the airway narrowing caused by smooth muscle shortening--especially if the wall thickening is localized in peripheral airways. The combination of a loss of recoil and airway wall thickening are more than additive in their effect on simulated airway responsiveness. We conclude that airway wall thickening and a loss of lung recoil can partially explain the airway hyperresponsiveness observed in patients with chronic obstructive lung disease and asthma. PMID- 1595988 TI - Early changes in T lymphocytes recovered by bronchoalveolar lavage after local allergen challenge of asthmatic airways. AB - To assess the role of T lymphocytes in the initiation of the allergic asthmatic response we have investigated T-cells subsets and their activation markers in bronchoalveolar lavage (BAL) fluid recovered 10 min after local challenge of the bronchial mucosa with allergen or saline. Endobronchial challenge was performed in 13 mildly atopic asthmatic patients (FEV1% predicted range, 78.2 to 116.5) and 10 normal volunteers. In all of the asthmatics but in none of the normal subjects allergen but not saline exposure resulted in visible bronchoconstriction. Analysis of BAL by flow cytometry showed no differences in the overall number of T cells (CD3+) and their CD4+ and CD8+ subsets per milliliter of BAL between the groups of normal subjects and asthmatics. However, within 10 min of allergen challenge, in the asthmatics but not in the normal subjects, there occurred a significant loss of CD3+ cells (p less than 0.01) comprising mostly CD4+ (p less than 0.05) but also CD8+ cells, with a consequent decrease in the CD4:CD8 ratio. At this early time point no differences in the extent of expression of the T-cell activation markers, IL-2 receptor, and HLA-DR were found. These results provide evidence to support a role of T lymphocytes early in the allergen-induced inflammatory response in asthma. PMID- 1595989 TI - Changes in the cellular profile of induced sputum after allergen-induced asthmatic responses. AB - Allergen inhalation causes airway inflammation and an increase in histamine airway responsiveness. We have used cell counts in sputum induced by hypertonic saline aerosol to assess airway inflammation before and 32 h after asthmatic responses to allergen. Twelve asthmatic subjects (mean age, 27.4 yr; range, 20-38 yr) had an inhalation test with D. farinae, ragweed pollen, or cat extract. All of them developed an early response with a fall in FEV1, of 24.8% (SD, 6.3%); nine of 12 had a definite late response (fall in FEV1 greater than or equal to 15%), and 10 of 12 had an increase in airway responsiveness to histamine at 32 h (PC20 reduced by greater than twofold). Sputum was induced by hypertonic saline after the histamine test, before and 32 h after the allergen challenge, at the same time of day. The quality of the sample was scored according to visual inspection and inverted microscopy and by salivary contamination. Plugs arising from the lower respiratory tract were selected for further evaluation. Differential cell counts of eosinophils (Eo) and metachromatic cells (MCC) (mast cell and basophils) were obtained from direct smears, blind to the clinical procedures. The mean fall in FEV1 after hypertonic saline was 6.4% (range, zero to 28%). The sputum samples were adequate in 79.5% of attempts. Eo and MCC increased significantly from 3.8 (4.4) to 18.2 (22.8)% (p = 0.01) and from 0.05 (0.17) to 0.25 (0.76)% (p = 0.04), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1595990 TI - Effect of an inhaled thromboxane mimetic (U46619) on airway function in human subjects. AB - Thromboxane A2(TxA2) has been implicated in the pathogenesis of airway hyperresponsiveness. The effects of inhaled TxA2 on human airway function have not been studied because of its short half-life. U46619 is a chemical that mimics the effects of TxA2. The purpose of this study was to evaluate the effects of inhaled U46619 on human airway function and methacholine airway responsiveness. Airway responsiveness to methacholine and U46619 was measured in 19 subjects (13 asthmatic and six normal) and expressed as the provocative concentration causing a 20% fall in FEV1 (PC20). On one day, methacholine alone was inhaled. On a second day, U46619 was inhaled, then 1 h later methacholine was inhaled. On a third day, U46619 was inhaled, then repeated 1 h later. In six subjects, the effects of isotonic saline or a subthreshold concentration of histamine or U46619 were examined on methacholine airway responsiveness. U46619 was 178 times more potent as a bronchoconstrictor than was methacholine. Airway responsiveness to methacholine was correlated to airway responsiveness to U46619 (r = 0.87, p = 0.001). Subthreshold concentrations of U46619, but not of histamine, increased methacholine airway responsiveness. The mean maximal fall in FEV1 after inhaled methacholine was 13.2% (SEM, 3.4%) after saline, 12.4% (SEM, 2.4%) after histamine, and 25.7% (SEM, 2.0%) after U46619 (p = 0.0004). This effect lasted less than 1 h. There was no tachyphylaxis to repeated inhalations of U46619. These results indicate that in human subjects inhaled U46619 is a potent bronchoconstrictor that, when present in the airways, can cause airway hyperresponsiveness to inhaled methacholine in asthmatic subjects. PMID- 1595991 TI - The effects of lipoxin A4 on airway responses in asthmatic subjects. AB - This study was performed to determine whether lipoxin A4 (LXA4) inhalation in asthmatic subjects has an effect on airways response. Eight subjects (six asthmatic, two normal) attended for bronchial inhalation challenge with LXA4. In three of these subjects (two asthmatics, one normal) blood pressure, pulse, and symptoms before and after challenge were recorded. Subsequently five male patients with mild asthma (22 to 34 yr of age) reattended for bronchial inhalation challenge with either leukotriene C4 (LTC4) or the combination of LTC4 and 1 x 10(-4) M LXA4. After inhalation of each dose of agonist SGaw and V25 were measured. Airway responsiveness was determined by the concentration of agonist in the nebulizer required to induce a 35% fall in SGaw (PC35). There was no effect of LXA4 inhalation on SGaw, V25, blood pressure, pulse, or symptoms. There was a significant shift of the SGaw and V25 dose-response curve to the right after inhalation challenge with LTC4 combined with 1 x 10(-4) M LXA4 as compared with that after inhalation challenge with LTC4 alone (p less than 0.01 and p less than 0.025, respectively). Thus, LXA4 may modulate LTC4-induced airway obstruction and may act as an endogenous sulfidopeptide leukotriene receptor antagonist. PMID- 1595992 TI - Prevention of exercise-induced bronchoconstriction by a new leukotriene antagonist (SK&F 104353). A double-blind study versus disodium cromoglycate and placebo. AB - The effects of 800 micrograms of inhaled SK&F 104353, a peptidoleukotriene receptor antagonist, and of 20 mg disodium cromoglycate (DSCG) on exercise induced bronchoconstriction were compared in 18 asthmatic patients. The study was conducted according to a double-blind, crossover, randomized, placebo-controlled design. Two baseline exercise tests were carried out, and pulmonary function tests were done before and at 1, 5, 10, 15, 20, and 30 min after completion of the exercise. Patients showing a 20% or greater decrease in FEV1 in both exercise challenges entered the blinded portion of the study. When placebo was administered before exercise, FEV1 fell to the same extent as during the baseline phase. After SK&F 104353 and DSCG, the bronchoconstriction was attenuated. The mean maximal percentage fall in FEV1 after exercise was 29% after placebo and 20% after SK&F 104353 and DSCG. The differences between the two active treatments did not reach the 5% level of statistical significance, though at 20 min SK&F 104353 showed a more pronounced effect than DSCG. The protective effect suggests an important role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction. PMID- 1595993 TI - Effect of dexamethasone and cyclosporin A on allergen-induced airway hyperresponsiveness and inflammatory cell responses in sensitized Brown-Norway rats. AB - We studied the effects of dexamethasone and cyclosporin A on the airway hyperresponsiveness (AHR) and the influx of inflammatory cells into the bronchoalveolar lavage (BAL) fluid seen 18 to 24 hr after exposure to aerosolized ovalbumin in actively ovalbumin-sensitized Brown-Norway rats. Allergen exposure resulted in an approximately sevenfold increase in bronchial responsiveness to inhaled acetylcholine associated with a significant increase in eosinophils and lymphocytes in BAL fluid. Dexamethasone (0.5 mg/kg administered intraperitoneally for 3 days) abolished the AHR and the increase in eosinophil and lymphocyte counts. However, cyclosporin A at two doses (5 and 50 mg given orally for 5 days) did not significantly prevent the induction of AHR while producing a significant inhibition of the eosinophil and lymphocyte influx. Dexamethasone (0.5 mg/kg for 3 days) or cyclosporin A (5 mg/kg for 5 days) on their own had no effect on airway responsiveness. We conclude that specific inhibition of T-lymphocyte activation in this Brown-Norway rat model is not sufficient to inhibit the induction of AHR despite suppressing allergen-induced eosinophilia in BAL fluid. However, corticosteroids, which have inhibitory effects on a wider range of inflammatory cells, are more effective. Our observations are in line with the potent effect of corticosteroids in airway inflammatory conditions such as asthma. PMID- 1595994 TI - Terbutaline acts at multiple sites to inhibit bronchoconstriction induced by dry air in canine peripheral airways. AB - We examined the effect of the beta 2-agonist terbutaline on dry airflow-induced bronchoconstriction (AIB) in the canine lung periphery. Using a wedged bronchoscope technique, collateral resistance (Rcs) and airway wall temperature (Taw) were measured before and after a 2-min exposure to dry air. When sublobar segments were challenged with dry air, Taw fell during challenge (p less than 0.001), and Rcs increased 5 min postchallenge (p less than 0.01). Pretreatment with terbutaline (100 micrograms/kg) reduced the fall induced by dry-air challenge in Taw by 37% and the subsequent rise in Rcs by 87%. Terbutaline significantly reduced the concentrations of thromboxane B2 (TxB2) and prostaglandin D2 (PGD2), and decreased the concentration of epithelial cells recovered in bronchoalveolar lavage fluid 5 min postchallenge. In addition, terbutaline attenuated histamine- and PGD2-induced constriction. Finally, peripheral lung sensitivity (as assessed by delta Rcs/delta Taw) to challenge after treatment with terbutaline was significantly less than that calculated for untreated control animals (p less than 0.05). These data are consistent with the idea that terbutaline attenuates AIB by (1) facilitating replacement of water lost during exposure to dry air, (2) inhibiting mediator production and release from osmosensitive cells, and (3) reducing smooth muscle responsiveness. PMID- 1595995 TI - Effect of acute and chronic antigen inhalation on airway morphology and responsiveness in actively sensitized rats. AB - Bronchial hyperresponsiveness (BHR) is a major characteristic of bronchial asthma. The pathogenesis of BHR remains to be fully elucidated, but is considered to be closely linked to airway inflammation. Animal models might provide us with useful data for a better understanding of the interrelationship between these phenomena. In the present study we investigated the effect of a single and chronic exposure to inhaled antigen on bronchial responsiveness and airway morphology in actively sensitized Brown Norway rats. Immunization to ovalbumin (OA) did not cause airway inflammation, but induced a small, transient decrease in bronchial responsiveness to 5-hydroxytryptamine (5HT) on Day 10, which returned to baseline on Day 16. By 24 h after a single exposure to aerosolized OA, a significant decrease in the provocative concentration of 5HT causing a 50% increase in lung resistance (PC50RL 5HT) was observed, compared with immunized, saline-exposed animals (7.7 +/- 0.8 versus 10.8 +/- 1.0 micrograms/kg). This was accompanied by the influx of neutrophils and few eosinophils in bronchoalveolar lavage fluid. Repeated daily or intermittent exposure to aerosolized OA enhanced airway inflammation, characterized by the presence of neutrophils, eosinophils, and lymphocytes in bronchoalveolar lavage fluid. Histologic analysis revealed patchy inflammatory infiltrates, located predominantly around bronchi and bronchioli. Despite these inflammatory changes, bronchial responsiveness was not significantly different from that of control animals. We therefore conclude that the induction of airway inflammation is not always associated with BHR. PMID- 1595996 TI - Alpha-1-protease inhibitor in bronchial asthma: phenotypes and biochemical characteristics. AB - The prevalence of the different phenotypes of alpha 1-protease inhibitor (alpha 1PI) was investigated in a group of 90 asthmatic patients and compared with that of a control group of 240 individuals representing the general population. The M2M2 phenotype occurred more frequently in the asthmatic group (p = 0.015). Plasma samples of 51 of the asthmatic patients randomly selected from the different phenotype groups identified were studied for the absolute plasma values of alpha 1-PI and the inhibitory capacity of plasma for porcine pancreatic elastase, and compared with those from 21 nonasthmatic individuals of the M1M1 phenotype. Although the asthmatic patients had higher absolute alpha 1PI values (p = 0.04), the plasma elastase inhibitory capacity was markedly reduced compared with the nonasthmatic subjects (p = 0.01). The functional efficiency of alpha 1PI from asthmatic patients of the M1M1, M1M2, and M2M2 phenotypes was significantly decreased compared with that of the nonasthmatic M1M1 individuals. Functional deficiency of alpha 1PI may be important in the pathogenesis of the inflammatory process that characterizes bronchial asthma. PMID- 1595997 TI - A self-complete measure of health status for chronic airflow limitation. The St. George's Respiratory Questionnaire. AB - A need was identified for a fixed-format self-complete questionnaire for measuring health in chronic airflow limitation. A 76-item questionnaire was developed, the St. George's Respiratory Questionnaire (SGRQ). Three component scores were calculated: symptoms, activity, and impacts (on daily life), and a total score. Three studies were performed. (1) Repeatability was tested over 2 wk in 40 stable asthmatic patients and 20 patients with stable COPD. The coefficient of variation for the SGRQ total score was 19%. (2) SGRQ scores were compared with spirometry, 6-min walking distance (6-MWD), MRC respiratory symptoms questionnaire, anxiety, depression, and general health measured using the Sickness Impact Profile score. A total of 141 patients were studied, mean age 63 yr (range 31 to 75) and prebronchodilator FEV1, 47% (range 11 to 114%). SGRQ scores correlated with appropriate comparison measures. For example, symptom score versus frequency of wheeze, r2 = 0.32, p less than 0.0001; activity versus 6-MWD, r2 = 0.50, p less than 0.0001; impact versus anxiety, r2 = 0.38, p less than 0.0001. Multivariate analysis demonstrated that SGRQ scores summed a number of areas of disease activity. (3) Changes in SGRQ scores and other measures were studied over 1 yr in 133 patients. Significant correlations were found between changes in SGRQ scores and the comparison measures (minimum r2 greater than 0.05, p less than 0.01). Multivariate analysis showed that change in total SGRQ score summed changes in a number of aspects of disease activity. We conclude that the SGRQ is a valid measure of impaired health in diseases of chronic airflow limitation that is repeatable and sensitive. PMID- 1595998 TI - Effect of intravenously administered aminophylline on ventilation/perfusion inequality during recovery from exacerbations of chronic obstructive pulmonary disease. AB - To investigate the effect of intravenously administered aminophylline and 100% O2 breathing on ventilation-perfusion (VA/Q) inequality, nine patients recovering from an acute exacerbation of chronic obstructive pulmonary disease (COPD) were studied. The design was double-blind, crossover, placebo-controlled for aminophylline, and a single-blind, controlled protocol for O2, patients being studied on two successive days. Forced spirometry, systemic hemodynamics, arterial pH, and blood gases were measured together with the VA/Q distribution using the multiple inert gas elimination technique, and then a loading dose of aminophylline (6 mg/kg body weight) or placebo was given over 20 min followed by a maintenance infusion at 0.9 mg/kg/h that was kept constant for the rest of the study. After 20 min of infusion the patient breathed either air or 100% O2 for another 30 min, and the measurements were repeated. Thereafter the inspired gas was shifted to the other FlO2 for 30 min, and a final set of measurements was made. The following day the procedure was repeated using the alternate drug. Aminophylline alone increased FVC and FEV1, but it produced no change in the group in ventilation, hemodynamics, blood gases, or the VA/Q distribution, although individual patients who had low VA/Q areas at baseline showed increases in these areas and worsening of log SD Q. Oxygen alone reduced cardiac output (QT) and caused modest further dispersion of the VA/Q distribution when compared with air breathing during placebo infusion (log SD Q 1.03 +/- 0.27 increased to 1.26 +/- 0.35, p less than 0.03).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596000 TI - Dyspnea and leg effort during incremental cycle ergometry. AB - The aim of this study was to establish the perceived magnitude of dyspnea (discomfort associated with breathing) and leg effort experienced by normal subjects during a standardized incremental exercise test to maximal capacity; 460 normal subjects (297 male and 163 female 20 to 70 yr of age) were studied. The perceptual magnitude of both symptoms was rated using simple descriptive phrases (slight, moderate, maximal) tagged to numbers from zero to 10 on the Borg scale, which is an interval scale with ratio properties. Leg effort and dyspnea increased with power output, were higher in women than in men (p less than 0.0001), increased with advancing age (p less than 0.0001), and declined as height increased (p less than 0.0001). Leg effort = 4.82 + 0.007 kpm/min + 1.05 sex + 0.04 age - 0.055 Ht (r = 0.78; SD, 1.80). Dyspnea = 4.96 + 0.006 kpm/min + 0.96 sex + 0.04 age - 0.05 Ht (r = 0.74; SD, 1.80) (m = 1; f = 2). With power output expressed as a percentage of maximal power output (%MPO) both symptoms increased in an alinear manner. Effort = 0.0014 * %MPO1.86 (r = 0.86; SD, 1.50). Dyspnea = 0.0016 * %MPO1.79 (r = 0.81; SD, 1.57). Sex, age, or stature did not contribute to the rating of effort or dyspnea when power output was normalized in this way. PMID- 1595999 TI - Pulmonary function abnormalities in chronic severe cardiomyopathy preceding cardiac transplantation. AB - Pulmonary function data, including diffusing capacity, were evaluated in 56 patients with chronic severe cardiomyopathy before heart transplantation. Cardiac catheterization data were used to describe the relationship between cardiac and pulmonary function. Of 56 patients 44 had some abnormality in pulmonary function. The majority, 30 of 56, had a restrictive impairment alone. Of 28 patients in whom diffusing capacity was measured, 64% had a diffusion impairment. There was no association of pulmonary function impairment with type of cardiomyopathy or smoking history. Pulmonary capillary wedge pressure correlated positively with DLCO, but not with FVC or TLC. Cardiac index and ejection fraction did not correlate with diffusing capacity. This precardiac transplantation cardiomyopathy patient group demonstrated frequent pulmonary function abnormalities not previously recognized. PMID- 1596001 TI - Prostaglandin E2 inhalation increases the sensation of dyspnea during exercise. AB - To clarify the role of vagal afferents from the lung in the sensation of dyspnea, we examined the effects of prostaglandin E2 (PGE2) inhalation on the sensation of dyspnea during exercise in eight normal male subjects. This intervention was chosen because inhaled PGE2 is known to stimulate vagal afferent receptors in the lung, in particular C-fiber endings, without a significant increase in airway resistance. After either physiologic saline or PGE2 aerosol (100 micrograms/ml) inhalation through a Bird nebulizer for 2 min, exercise tests were performed on a bicycle ergometer. The tests consisted of 3 min at rest followed by graded work loads (zero to 150 watts, 50-watt increments). Minute ventilation (VE) and respiratory rate were monitored from an expiratory line through a face mask. Oxygen consumption (VO2) and carbon dioxide production (VCO2) were calculated from samples of mixed expired gas. The sensation of difficulty in breathing (dyspnea) was measured on a modified Borg scale at rest and at the end of each work load. We found that although airway resistance and lung volume did not change significantly between saline and PGE2 inhalations, inhaled PGE2 significantly increased the magnitude of the dyspneic sensation when compared with inhaled saline at the same levels of work load, ventilation, and oxygen consumption. These results suggest that in addition to probable roles of motor command and chemical drive, afferent vagal activity from the lung also contributes to the sensation of dyspnea during exercise. PMID- 1596002 TI - Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin. AB - Although it is known that endotoxin can induce diaphragmatic dysfunction, the mechanism of this effect is not fully understood. However, because the effects of endotoxin on other tissues appear to be mediated in part by free radicals, the present study sought to determine if free radicals may also contribute to the diaphragmatic dysfunction induced by endotoxin administration. Studies were performed on four groups of hamsters. One group of animals received intraperitoneal injections of endotoxin on the first and second days of study (i.e., 10 and 20 mg/kg, respectively). The second group received saline rather than endotoxin, the third group received both endotoxin and a free radical scavenger, PEG-SOD (2,000 U/kg given intraperitoneally every 12 h on Days 1 and 2), and the fourth group received PEG-SOD alone. All groups were killed on the third study day (i.e., 48 h after the initial injections). Diaphragmatic contractile function was assessed in vitro using muscle strips excised from the costal diaphragms of freshly killed animals; diaphragm samples were also assayed for malondialdehyde (MDA), a commonly used index of free-radical-mediated lipid peroxidation. MDA levels were higher in diaphragms from endotoxin-treated animals than from saline-treated control animals, and the contractility of diaphragm strips from endotoxin-treated animals was reduced when compared with strips from saline-treated control animals. Administration of PEG-SOD prevented MDA formation and contractile dysfunction in endotoxin-treated animals. Diaphragm contractility and MDA levels for animals given PEG-SOD alone were similar to those for saline treated control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596003 TI - Effect of therapeutic theophylline levels on the sleep quality and daytime cognitive performance of normal subjects. AB - The effect of theophylline on sleep quality and cognitive performance in patients with obstructive lung disease has been the subject of controversy. To examine the direct effects of theophylline on sleep quality and cognitive performance, without confounding effects from bronchodilatation, we have undertaken a study of the drug in healthy subjects. A double-blind, placebo-controlled crossover protocol was used to study the effect of oral sustained-release theophylline (Theodur) on subjective sleep quality, objective sleep quality, and cognitive performance. Overnight sleep studies were carried out on Nights 13 and 14 of each 2-wk study limb, and cognitive performance tests administered on Days 1 and 13 of each limb. A total of 18 subjects satisfactorily completed the study (8 males, median age 37, range 24 to 67 yr). Theophylline levels were median 10.2, range 2.3 to 13.3 micrograms/ml on Day 1 and 14.7, range 9.6 to 17.5 micrograms/ml on Day 13. No significant difference was observed between theophylline and placebo on subjective or objective sleep quality or on acute or medium-term cognitive performance. We conclude that theophylline does not affect sleep quality or cognitive performance in normal adults. PMID- 1596004 TI - Control of breathing in patients with myasthenia gravis. AB - Control of breathing has seldom been investigated in patients with myasthenia gravis (MG). We evaluated lung volumes and respiratory muscle strength by measuring maximal inspiratory (MIP) and expiratory (MEP) pressures in 12 patients with moderate generalized (IIb) MG before and after an orally administered therapeutic dose (120 mg) of Mestinon, and in 11 age- and sex-matched normal subjects. Breathing pattern, mouth occlusion pressure (P0.1), and surface electromyographic activity of the diaphragm (EMGd) and intercostal (EMGint) muscles were evaluated during both room-air breathing and hypercapnic rebreathing. Before Mestinon, patients exhibited a slight decrease in VC, and normal TLC and FEV1/VC ratio. Compared with the normal control group, patients also exhibited respiratory muscle weakness (marked decrease in MIP and MEP; p less than 0.001 for both), and more rapid and shallower breathing (RSB): lower tidal volume (VT), inspiratory time (TI), expiratory time (TE), and greater respiratory frequency (f); mean inspiratory flow (VT/TI) and P0.1 were slightly supernormal, whereas both EMGd and EMGint were significantly higher in patients. During hypercapnic rebreathing, ventilation (VE) (p less than 0.001), VT (p less than 0.001), VT/TI, (p less than 0.003), P0.1 (p less than 0.003), and EMGd (p less than 0.001) response slopes to increasing PCO2 were found to be lower, whereas EMGint response slope was normal. At 60 mm Hg of PCO2 in the two groups the difference in terms of breathing pattern, P0.1, and EMGd were similar to that observed during room-air breathing. After Mestinon, VC (p less than 0.005), MIP (p less than 0.02), and MEP (p less than 0.01) significantly increased, whereas spontaneous breathing remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596005 TI - Diurnal and nocturnal diuresis and natriuresis in obstructive sleep apnea. Effects of nasal continuous positive airway pressure therapy. AB - Excessive nocturnal diuresis and natriuresis have been reported in patients with sleep apnea. The mechanisms responsible for these alternations in nocturnal renal function have not been clearly identified. To gain further insight into this matter, we studied 12 patients (one woman) with a mean +/- SD age of 50 +/- 9 yr and body mass index of 36.9 +/- 8.6 kg/m2. Polysomnography showed in all a sleep apnea syndrome with an apnea-hyponea index (AHI) of 81.3 +/- 41.7. Treatment with nasal continuous positive airway pressure (nCPAP) resulted in an AHI of 19.4 +/- 13.7 and in normalization of sleep characteristics. Diurnal renal function was normal in all subjects. Although untreated, patients showed an abolition of the well-known decrease in diuresis and natriuresis during the night (diurnal and nocturnal diuresis 56.3 +/- 26.8 and 77.2 +/- 33.4 ml/h, respectively, p = NS; diurnal and nocturnal fractional urinary Na+ excretion 0.42 +/- 0.09 and 0.70 +/- 0.55 ml/100 ml glomerular filtration [GF], respectively, p = NS). Results of nocturnal studies under nCPAP therapy showed a significant decrease in diuresis and natriuresis (nocturnal diuresis before and under nCPAP, respectively: 90.4 +/ 27.3 and 70.6 +/- 25.1 ml/h, p less than 0.02; nocturnal fractional urinary sodium excretion before and under nCPAP, respectively: 0.76 +/- 0.53 and 0.44 +/- 0.37 ml/100 ml GF, p less than 0.03). Morning blood levels of renin, aldosterone, antidiuretic hormone, epinephrine, and atrial natriuretic factor showed no significant difference before and under nCPAP, whereas norepinephrine significantly decreased from 309.5 +/- 104.2 before to 230.4 +/- 88.4 pg/ml under nCPAP (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596006 TI - Tidal breath flow-volume curves in obstructive sleep apnea. AB - Because of the gravitational position during sleep and the associated relaxed state, we hypothesized that passive expiration in the supine position might reflect upper airway pathophysiology in obstructive sleep apnea (OSA). We prospectively enrolled and tested 92 subjects with several clinical conditions. Maximal comfort and relaxation during expiration was achieved by connecting subjects to a ventilator via a mouthpiece. An initial respiratory rate of 16 breaths/min and tidal volume of 10 ml/kg were selected. Fine adjustments were then made to achieve maximal subject relaxation. Using this method, we obtained reproducible tidal breath flow-volume curves (TBFVC). Testing was performed in both sitting and supine positions. Standard pulmonary function tests, including spirometry and lung volume measurements, were also obtained in both sitting and supine positions. Of 86 patients who could be evaluated, 12 (60%) of 20 subjects with documented OSA (respiratory disturbance index: mean, 64.8; range, 10 to 120.5) demonstrated a positional change in the terminal portion of the TBFVC; 10 (32%) of 31 with a history of snoring also tested positive, but only three (9%) of 35 subjects with no OSA, by polysomnography (n = 8) or questionnaire (n = 27), demonstrated such a positional change. This positional change in TBFVC, which was significantly more frequent in subjects with OSA, could not be attributed to any measurable pulmonary function abnormality or body mass index. We believe this positional change in TBFVC reflects upper airway functional narrowing induced by assumption of supine position and decreasing airflow rates. PMID- 1596007 TI - Effects of enhancing slow-wave sleep by gamma-hydroxybutyrate on obstructive sleep apnea. AB - Sleep apneas are rarely observed during slow-wave sleep (SWS), which is poorly represented in patients with obstructive sleep apnea (OSA). Gamma-hydroxybutyrate (gamma OH), a natural metabolite of the brainstem, increases the percentage of total sleep time (TST) spent in SWS. We evaluated the effects of gamma OH on sleep and breathing disorders in eight patients with OSA (age, 45 +/- 2 yr; body mass index, 35.0 +/- 1.5 kg/m2; mean +/- SEM). Three conventional sleep studies were done within a week; the first and third were control studies, and the second was the gamma OH study (30 mg/kg at bedtime and 3 h later). Because the effects of the drug last only 3 h, we analyzed and compared the results of the first 6 h of sleep recording. The percentage of TST spent in SWS increased with gamma OH (30.7 +/- 3.9%) compared with that in the control studies (12.5 +/- 1.1 and 11.0 +/- 2.1%) at the expense of stages I and II. There was no difference between apnea index obtained during the control studies (26.3 +/- 5.3 and 25.4 +/- 6.2/h) and that obtained during the gamma OH study (29.6 +/- 4.9/h). Most apneic events occurred during Stages I and II, and REM, but this proportion was less during the gamma OH study (77.9 +/- 8.9%) than during the control studies (92.3 +/- 1.9 and 95.9 +/- 2.2%), apneas occurring even during SWS with gamma OH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596008 TI - Augmented heart rate response to hypoxia in patients with chronic obstructive pulmonary disease. AB - Effects of acute, progressive isocapnic hypoxia on heart rate (HR) and ventilation were determined in 31 patients with chronic obstructive pulmonary disease (COPD) and in 24 normal control subjects. There was an inverse linear relationship between heart rate and SaO2 in each subject. The slope factor (delta HR/delta SaO2) obtained from the regression line was significantly higher in the patients with COPD than in the normal control subjects (0.888 +/- 0.309 SD beats/min/% fall in SaO2 versus 0.693 +/- 0.287; p less than 0.05), whereas the ventilatory response (delta VE/delta SaO2) was not significantly different between the two groups. To elucidate factors responsible for the augmented heart rate response to hypoxia in the patients with COPD, we examined the relationships of delta HR/delta SaO2 with age, physical characteristics, pulmonary function data, and arterial blood gas data in all the subjects. A weak but significant relationship was found only between delta HR/delta SaO2 and FEV1/VC, %FEV1, RV/TLC, and %RV. Because the HR response to hypoxia correlates only with parameters that reflect the grade of airway obstruction, we believe that the enhanced HR response seen in patients with COPD is a result of the disease process in the airway and tissue, although the precise mechanism was not specified in this study. PMID- 1596009 TI - Pulmonary and oxygen transport effects of intravenously administered endotoxin in normal humans. AB - Little data are available describing the initial changes in pulmonary function and oxygen transport during human endotoxemia. We studied 26 normal humans after intravenously administered endotoxin (4 ng/kg). To evaluate alterations in gas exchange, hemodynamic monitoring was performed in nine subjects given endotoxin and six subjects given saline only. Compared with the control subjects, no changes in gas exchange occurred at 3 h, but after volume loading (mean, 2.2 L saline infused from 3 to 5 h) the PaO2 fell (86.1 +/- 2.3 mm Hg, p = 0.042), and the AaPO2 widened (18.5 +/- 1.7 mm Hg, p = 0.005). Oxygen consumption and delivery both increased significantly at 3 h (219 +/- 17 and 1,030 +/- 43 ml/min.min2) and 5 h (203 +/- 7 and 949 +/- 48 ml/min.min2) (p less than or equal to 0.035), whereas oxygen extraction fell at 3 h (p = 0.041). Seventeen subjects underwent bronchoalveolar lavage 14 +/- 4 days before and at 1.5 to 3 h (n = 8) or 5 h after (n = 9) the administration of endotoxin. No increase in the total number of cells or percent or absolute number of neutrophils was found at either time point. The rate of clearance of inhaled 99mTc-diethylenetriamine pentacetate aerosol, a measure of alveolar epithelial permeability, increased in subjects scanned before 3 h (n = 8; p less than 0.05), whereas no significant changes occurred in subjects scanned 5 h after endotoxin (n = 5) or in control subjects (n = 6). Early inflammatory responses after intravenous administration of endotoxin to normal humans results in alterations in gas exchange and lung permeability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596010 TI - Release of von Willebrand factor antigen (vWF:Ag) and eicosanoids during acute injury to the isolated rat lung. AB - It has been suggested that the von Willebrand factor antigen (vWF:Ag) may be a clinical marker for pulmonary endothelial cell injury. An ELISA was developed for the measurement of rat vWF:Ag. Rat lungs were isolated and perfused with a recirculating, blood-free, physiologic salt solution. Circulating levels of vWF:Ag and the eicosanoids thromboxane B2 (TXB2) and prostaglandin 6-keto F1 alpha (6-keto PGF1 alpha) were measured before and after different forms of insult. The addition of phospholipase C (PLC) or hydrogen peroxide (H2O2) to the perfusate caused lung damage as manifested by pulmonary artery pressure increase and pulmonary edema. This was paralleled by significant release of vWF:Ag, TXB2, and 6-keto PGF1 alpha. Increased hydrostatic pressure caused pulmonary edema without vWF:Ag and eicosanoid release. The addition of vasopressin to the perfusate caused vWF:Ag release but no lung injury and no release of eicosanoids. It is concluded that in the rat model, vWF:Ag release is a nonspecific marker for lung injury. PMID- 1596011 TI - In vitro conversion of surfactant subtypes is altered in alveolar surfactant isolated from injured lungs. AB - Pulmonary alveolar surfactant can be separated into different subtypes on the basis of their buoyant densities. These subtypes have been characterized as ultraheavy and heavy forms, which are surface-active, and light forms, which are less surface active. The ratio of these subtypes was altered in an animal model of acute lung injury that contributed to the physiologic abnormalities. We used an in vitro method of surface-area cycling to compare conversion of heavy subtypes isolated from injured and from normal lungs. Lung injury was induced in adult rabbits with a subcutaneous injection of N-nitroso-N-methylurethane (NNMU). Conversion of NNMU-injured heavy subtypes to light subtypes was significantly greater than normal heavy subtype conversion at each time point studied from 60 to 180 min of cycling (p less than 0.01). Surfactant protein A (SP-A) was added to heavy subtypes, with no effect on conversion when 1.5% SP-A was added, but the addition of 4.5, 10.5, and 22.5% caused complete conversion to ultraheavy forms with no cycling. With subsequent cycling, there was greater conversion from ultraheavy to lighter subtypes for normal surfactant material than for NNMU injured material (p less than 0.05). We conclude that the altered ratio of surfactant subtypes in the alveolar lavage of injured lungs was due to a greater conversion of these subtypes within the alveolar space. Furthermore, SP-A may play an important role in the metabolism of alveolar surfactant both in normal and in injured lungs. PMID- 1596012 TI - Diagnosis of histoplasmosis in patients with the acquired immunodeficiency syndrome by detection of Histoplasma capsulatum polysaccharide antigen in bronchoalveolar lavage fluid. AB - Diagnosis of histoplasmosis in patients with Acquired Immunodeficiency Syndrome (AIDS) may be established by detection of the organism in lung tissue or bronchoalveolar lavage fluid. In this report we have evaluated the utility of Histoplasma capsulatum polysaccharide antigen (HPA) detection in bronchoalveolar lavage fluid for diagnosis of histoplasmosis. HPA was detected in bronchoalveolar lavage fluid of 19 of 27 cases (70.3%). Of 122 controls with a variety of underlying diseases, HPA was detected in none. Eight of the negative specimens from patients with histoplasmosis were retested after fivefold concentration, and HPA was detected in five. Fivefold concentration of 10 control samples had no effect on HPA level. H. capsulatum was seen by methenamine silver or Giemsa stain in 19 of the 27 (70.3%) and isolated by culture in 24 of 27 (88.9%) cases. Twenty four of 26 (92.3%) cases had positive cultures from extrapulmonary sites as well. HPA was detected in the urine of 25 (92.6%) and the serum of 23 (88.5%) of the 26 cases. We conclude that HPA detection offers a rapid method for identification of pulmonary histoplasmosis in patients with AIDS and could be a helpful addition to the battery of tests performed on bronchoalveolar lavage fluids in areas where histoplasmosis is endemic. PMID- 1596013 TI - Cost reduction in diagnosing Pneumocystis carinii pneumonia. Sputum induction versus bronchoalveolar lavage as the initial diagnostic procedure. AB - Sputum induction (SI) is a sensitive and specific method for diagnosing Pneumocystis carinii pneumonia (PCP) in patients with AIDS. Although less expensive than bronchoscopy with bronchoalveolar lavage (BAL), SI followed by BAL does not necessarily reduce costs compared with BAL alone. Cost analysis demonstrates that the cost of diagnosing PCP is dependent on the prevalence of PCP (PCPprevalence) in the studied population, the sensitivity of SI (SIsensitivity) for diagnosing PCP, and the relative costs of SI and BAL (SIcost and BALcost) for diagnosing PCP. In any given clinical setting, SI reduces the cost of diagnosing PCP if (PCPprevalence)(SIsensitivity) greater than SIcost/BALcost. A graphic approach relating these parameters is also presented. Evaluation of reported PCPprevalence and SIsensitivity from recent literature illustrates that SI is not always the least costly method for diagnosing PCP. Cost reduction is not the only measure of a diagnostic procedure's value, and other aspects, such as discomfort, availability, risks, and patient prognosis, must be considered. The cost analysis approach used in this study identifies those variables that can be manipulated to reduce the cost of diagnosing PCP. PMID- 1596014 TI - Tuberculous pleural effusion: 6-month therapy with isoniazid and rifampin. AB - We have shown that 6-month therapy with isoniazid (INH) and rifampin (RIF) is adequate for pulmonary tuberculosis when tubercle bacilli are less numerous, i.e., smear negative, culture positive. Tuberculous exudative pleural effusion contains small bacterial populations, as often demonstrated by negative smears and fewer positive cultures. Therefore, in 1980, we started treating tuberculous pleural effusion with a therapy protocol consisting of INH 300 mg plus RIF 600 mg daily for 1 month, followed by INH 900 mg plus RIF 600 mg twice weekly for another 5 months (total, 6 months). From January 1980 to September 1990, 198 patients with an average age of 62.6 years were treated in this manner. Associated pulmonary infiltration was present in 92 patients, of whom 50% yielded positive sputum cultures. Other medical conditions as "risk factors" were present in 30%. Therapy was not completed in 36 patients because of death, relocation, noncompliance, and drug side effects. Treatment failed during therapy in only 1 patient. Side effects of the drugs occurred in 13 (6.6%) patients, but major side effects were encountered in only three (1.5%), two with toxic hepatitis and one with thrombocytopenia. The full 6-month therapy was completed by 161 patients. During follow-up from 2 to 133 months (median, 46 months), none of the 161 patients had relapse. An overall success rate of 99% was achieved in 162 patients with only 1 failure during therapy. Thus, 6-month therapy with INH plus RIF is adequate in tuberculous exudative pleural effusion, even when associated with smear-negative (3 specimens) culture-positive pulmonary tuberculosis. PMID- 1596015 TI - Neutrophilic alveolitis in idiopathic pulmonary fibrosis. The role of interleukin 8. AB - Idiopathic pulmonary fibrosis is an immunologically mediated pulmonary disorder in which activated alveolar macrophages (AM) and neutrophils play cardinal roles in the pathogenesis of the inflammatory lung lesion. The factors responsible for the induction and perpetuation of the neutrophilic alveolitis are not known. Recently, a novel cytokine (Interleukin-8) was described that is released by activated mononuclear phagocytes and a variety of other cell types, and it exhibits potent chemotactic activity for polymorphonuclear leukocytes (PMN). Increased expression of IL-8 has been described in other inflammatory disorders characterized by neutrophilic infiltration, including psoriasis, rheumatoid arthritis, and the sepsis syndrome, but no studies have assessed this cytokine in the context of interstitial pulmonary disorders. We have previously shown that normal human AM release IL-8 upon appropriate stimulation, but data assessing the expression of IL-8 by human AM in specific pulmonary disease states are lacking. In this study, we examined the expression of steady-state mRNA for IL-8 by human alveolar macrophages obtained by bronchoalveolar lavage (BAL) from patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis and from healthy volunteers. Because it is known that adherence to plastic culture plates may up-regulate gene expression for IL-8 in the absence of additional stimulation, we extracted mRNA immediately from the cell pellet obtained by BAL rather than using cultured alveolar macrophage monolayers. Northern blot analysis was performed to determine IL-8 mRNA expression. We found that BAL cells from patients with IPF constitutively expressed mRNA for IL-8, and the amount of IL-8 mRNA (as assessed by laser densitometry) correlated with the percent of neutrophils on BAL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596016 TI - Increased intestinal permeability in active pulmonary sarcoidosis. AB - Altered permeability of the gut is a well-described feature in Crohn's disease. Because of pathologic similarities between Crohn's disease and sarcoidosis, we initiated this study to evaluate the permeability of the gut mucosal lining in patients with pulmonary sarcoidosis. A group of 18 patients with biopsy-proven pulmonary sarcoidosis (active n = 8, inactive n = 10) were included in the study. Control groups included 22 patients with Crohn's disease (active n = 12, inactive n = 10), nine untreated patients with recent pulmonary tuberculosis, six patients with coal worker's pneumoconiosis (CWP), eight patients with idiopathic pulmonary fibrosis (IPF), and 16 healthy subjects. All were nonsmokers. The 24-h urinary excretion of 100 microCi 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) was used to test the intestinal permeability (IP). As previously demonstrated, patients with active Crohn's disease demonstrated a dramatic increase in IP (7.7 +/- 1.4%) that was clearly reduced in inactive CD (2.34 +/- 0.54%). Patients with active pulmonary sarcoidosis exhibited a marked increased IP to 51Cr-EDTA (4 +/- 0.54%), which was not found in patients with inactive sarcoidosis (1.6 +/- 0.17%). IP was normal in patients with pulmonary tuberculosis (1.03 +/- 0.25%), CWP (2.1 +/- 0.54%), and IPF (1.9 +/- 0.33%) and did not differ from the control group (1.76 +/- 0.23%). In addition, in 6 patients with active pulmonary sarcoidosis, the concentrations of albumin and hyaluronan were measured in jejunal perfusion fluid and compared with those obtained from 10 patients with active Crohn's disease and 16 control subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596017 TI - Stress failure of alveolar epithelial cells studied by scanning electron microscopy. AB - Stress failure of capillary walls has previously been demonstrated in anesthetized rabbit lungs at high capillary transmural pressures, and the ultrastructural changes in the walls have been described with transmission electron microscopy. In the present study, the pattern of alveolar epithelial disruptions was studied using scanning electron microscopy (SEM). Lungs of anesthetized rabbits were perfused with autologous blood at capillary transmural pressures of 12.5, 32.5, 52.5, and 72.5 +/- 2.5 cm H2O and fixed by intravascular perfusion. Samples for SEM were processed by critical point-drying and freeze drying, and the results of the two techniques agreed well. Out of a total of 433 alveolar epithelial breaks examined, 93% were elongated, with the remainder being roughly circular; 68% of the elongated breaks were oriented perpendicular to the capillary axis, suggesting that the surface tension of the alveolar lining layer played an important role in protecting the blood-gas barrier against stress failure. Most of the breaks involved the full blood-gas barrier, but 17% were limited to the epithelial cells. This finding is consistent with our earlier conclusion that the extracellular matrix, particularly the type IV collagen, is responsible for much of the strength of the blood-gas barrier. The dimensions of the elongated breaks of the epithelium were approximately 4 microns (length) and 1 micron (width). They varied little with pressure, suggesting that once the disruption had occurred the stresses were greatly relieved. Breaks affecting the complete blood-gas barrier tended to be larger than those confined to the epithelium, again consistent with the protective role of the extracellular matrix. Almost no breaks occurred at intercellular junctions although many were seen within 1 micron of the junctions. This finding suggests that the junctions themselves have considerable mechanical strength, but that their rigidity may make the cell in the vicinity of the junction more vulnerable to mechanical failure. PMID- 1596018 TI - Effect of thyroid hormone on in vivo contractility of the canine diaphragm. AB - This study was designed to examine the effects of long-term (4 wk) administration of thyroid hormone on the in vivo contractility of the canine diaphragm. We implanted a pair of piezoelectric crystals chronically in the left crural and costal parts of the diaphragm by a midline laparotomy. Contractility was assessed by changes in the shortening of muscle fibers after twitch stimulation of both the crural and the costal parts of the diaphragm and in the transdiaphragmatic pressure (Pdi) after tetanic stimulation (10 to 100 Hz). As a reference, we also studied the response of the quadriceps femoris. Pretreatment measurements were taken 2 wk after surgery. Then, dogs assigned to the hyperthyroid group were given thyroid powder, 0.6 g/kg/day, orally for 4 wk. The control group was fed a diet without thyroid powder for 4 wk. Serum free-T4 level (RIA) in the hyperthyroid group (n = 9) increased from 0.68 +/- 0.07 to 5.72 +/- 0.95 ng/dl (mean +/- SE) (p less than 0.01). Pdi decreased 30 to 40% at all frequencies (p less than 0.05) except 10 Hz. Twitch shortening of the crural and costal parts, compared with pretreatment state, decreased significantly by 47.7 +/- 13.1 and 48.1 +/- 15.0%, respectively (p less than 0.05). The maximal rate of relaxation became significantly faster, by 63.5% (p less than 0.05), in the crural part, whereas that of the costal part tended to become faster but not to a significant extent. In the quadriceps femoris, although twitch force showed no change, both the maximal rate of contraction and maximal rate of relaxation became faster, and tetanic force decreased. Histologic examination of hyperthyroid dogs showed vacuolization and loss of fiber area of the diaphragm. These observations suggest that thyroid hormone impairs contractility of both the crural and costal parts of the diaphragm similarly, and that the decrease in contractility may be due to a loss of muscle mass and summation impairment of twitch contraction, which differs from that in other skeletal muscles. PMID- 1596019 TI - Direct effects and augmentation of airway smooth muscle contraction caused by phospholipase A2. AB - We examined the effect of phospholipase A2 (PLA2; Naja naja) on isometric tracheal smooth muscle force generation in guinea pig trachealis in situ. Direct application of PLA2 to the surface of the trachea caused dose-related contraction of tracheal smooth muscle. In seven guinea pigs, a dose/density of 100 micrograms/cm2 PLA2 caused active tension (AT) that began immediately and was maximum (1.32 +/- 0.13 g/cm) at 5 min (p less than 0.01 versus baseline tension). PLA2 also augmented the contractile response to intravenously administered acetylcholine (ACh); AT caused by 3 x 10(-7) mol/kg ACh was 0.98 +/- 0.13 g/cm after PLA2 versus 0.64 +/- 0.09 g/cm in control animals (p = 0.003). PLA2 inactivated with bromophenacyl bromide (BPB) prior to topical application neither caused contraction (-0.18 +/- 0.18 g/cm AT, p = NS versus baseline tension) nor altered muscarinic responsiveness to 3 x 10(-7) mol/kg ACh. Contraction caused by 100 micrograms/cm2 PLA2 was greater after epithelium removal (2.73 +/- 0.40 g/cm AT versus 1.32 +/- 0.13 g/cm AT in epithelium-intact animals, p less than 0.005). However, epithelium removal (confirmed histologically) attenuated completely augmentation of muscarinic contraction caused by PLA2. Augmentation of muscarinic contraction also was blocked with 15 mg/kg 3-amino-1-(3-trifluoromethylphenyl)-2 pyrazoline hydrochloride (BW 755c), an inhibitor of eicosanoid synthesis, administered intravenously 30 min prior to topical application of 100 micrograms/cm2 PLA2. In contrast, contraction of tracheal smooth muscle caused by PLA2 was not affected significantly by blockade of eicosanoid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596020 TI - Airway hyperresponsiveness, increased intracellular spaces of bronchial epithelium, and increased infiltration of eosinophils and lymphocytes in bronchial mucosa in asthma. AB - Inflammation of the airway wall and airway hyperresponsiveness are consistent features of chronic asthma. We investigated how damage of the bronchial epithelium is related to airway hyperresponsiveness and how bronchial infiltration of eosinophils and lymphocytes is related to bronchial epithelial damage. We examined the biopsy specimens of bronchial mucosa taken from 19 patients with chronic asthma by electron microscopy. We also measured the incidence of opening of epithelial tight junctions, the widening of intercellular spaces in the epithelium, and the density of infiltrated eosinophils and lymphocytes in bronchial mucosa. Airway responsiveness was accessed by measuring PC20-acetylcholine (PC20-ACh). The inflammatory cells in the airway mucosa were counted by electron microscopy. Lymphocytes were most abundant, being 54.5% of the cells counted; eosinophils were 22.1%, neutrophils were 4.9%, and mast cells were 4.6%. A significant correlation was noted between the density of eosinophils and that of lymphocytes infiltrated in the airway mucosa (r = 0.80, p less than 0.01), suggesting that T cells may potentiate eosinophil infiltration. With increased density of eosinophils infiltrated in bronchial mucosa, both the incidence of opening of tight junctions of epithelial ciliary cells and the degree of widening of intercellular spaces in epithelium increased significantly (r = 0.51, p less than 0.05; r = 0.52, p less than 0.05), suggesting that eosinophils are related to damage of the bronchial epithelium. No correlation was observed between the density of lymphocyte infiltration and the degree of epithelial damage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596021 TI - T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis. AB - With the use of monoclonal antibodies (mAb) and immunohistology, the numbers of phenotypically distinct cells infiltrating lung tissue from 15 postmortem (PM) cases of fatal asthma were quantified and compared with 6 cases of cystic fibrosis (CF) (three postmortem, three transplant) and 10 nonasthmatic cases of sudden death matched for age and sex. Tissue eosinophilia was significantly greater (p less than 0.001) in the fatal asthma group than in the CF or sudden death controls. In asthma, approximately 40% of the eosinophilic infiltrate was EG2 positive (an indication of eosinophil activation and secretion of eosinophil cationic protein). The numbers of eosinophils and EG2 positive cells were significantly elevated in the subjects with acute severe asthma who had had a duration of terminal illness exceeding, as compared with less than, 24 h (p less than 0.05). When compared with the sudden death controls, there were increases in the numbers of Dako L C positive cells (i.e., CD45 positive "total leukocytes") in both fatal asthma and CF (p less than 0.01 and 0.05, respectively). The mean number of MT-1 positive (T) cells in the asthma and CF groups was approximately twice that of the control (p less than 0.05 and 0.01, respectively). The mean number of MB2 positive (B) cells was similar for both the asthma and sudden death control groups but was significantly increased in CF (p less than 0.05). The average T:B cell ratios were 6:1, 1:1, and 2:1 in the fatal asthma, CF, and control groups, respectively. The results support a role for the T lymphocyte in the pathogenesis of fatal asthma and CF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596022 TI - Aspergillus epidural abscess and cord compression in a patient with aspergilloma and empyema. Survival and response to high dose systemic amphotericin therapy. AB - A 57-yr-old man with a chronic lung cavity presumed to be related to ankylosing spondylitis and/or old cavitary tuberculosis presented with hemoptysis and rapidly developed lower extremity paresis and hypoesthesia. On chest radiograph he had a left upper lobe lesion suggestive of aspergilloma combined with a large left empyema with bronchopleural fistula. Serologic analysis demonstrated precipitins and very high titer IgG antibodies to Aspergillus fumigatus antigens. Decompressive laminectomy from T1 to T5 was performed, with drainage of A. fumigatus culture-positive material from an epidural abscess compressing the spinal cord. Chest drainage was required for control of the empyema. With a total course of 3 g of intravenously administered amphotericin B, rehabilitative therapy, and chronic empyema drainage, he is now at home and ambulatory with assistance. He is also being followed by regular serum assays of IgG antibodies to Aspergillus proteins. We report the case of an apparent long-term survivor of a formerly lethal and/or nonreversible paraplegic condition. The critical factors compared with previous cases with a poor outcome would appear to be prompt neurosurgical intervention, restoration of a normal number of T-cells, effective long-term chest drainage, and high dose amphotericin treatment. PMID- 1596023 TI - Pseudoaneurysm of pulmonary artery in mucormycosis. Radiographic characteristics and management. AB - Pulmonary mucormycosis is a rare and almost invariably fatal complication that can occur in the context of severe deficits in host defenses. Antemortem diagnosis is difficult and requires a high index of suspicion together with invasive diagnostic techniques. Mucor species exhibit a pronounced affinity to invade vessels; mucormycosis involving the pulmonary vasculature has rarely been documented antemortem, and survival in this context has been rare. In this report, we describe a patient with chronic renal failure and systemic lupus erythematosus who developed extensive invasion of the left main pulmonary artery by mucormycosis. Chest computed tomographic (CT) scans and pulmonary arteriogram demonstrated a massive pseudoaneurysm of the left pulmonary artery; these radiographic findings have not previously been described in mucormycosis. Aggressive combination therapy, employing preoperative amphotericin B (AmB) followed by surgical resection (pneumonectomy) and a full course of AmB, was curative. This favorable outcome supports the role of surgery as adjunctive therapy, and it underscores the need for early diagnosis and aggressive treatment. PMID- 1596024 TI - Gene analysis of heterozygous protein C deficiency in a patient with pulmonary arterial thromboembolism. AB - A 16-yr-old male patient with heterozygous protein C deficiency developed acute pulmonary thromboembolism. The patient had low levels of plasma protein C antigen and activity (33 and 35% of normal, respectively). Analysis of the protein C gene by polymerase chain reaction (PCR) and direct sequencing revealed a nucleotide substitution (Arg169CGG----Trp169 TGG) in exon VII. This mutation is identical with protein C Tochigi, and the substituted amino acid is located at the cleavage site of the activation peptide of protein C. The mutant sequence was also detected in the mRNA transcripts of protein C gene. These results suggest that the possible mechanism of plasma protein C reduction is impaired stability or susceptibility to protein degradation during intracellular processing or after secretion into plasma. As this is a third independent case of protein C Tochigi with thromboembolism, the mutation of Arg169 (CGG) to Trp169 (TGG) in the protein C gene may be a "hot spot" and a common type of genetic lesion in congenital protein C deficiency with thromboembolic complications. PMID- 1596025 TI - Pulmonary vascular permeability in interstitial lung disease. A positron emission tomographic study. AB - We evaluated pulmonary vascular permeability with positron emission tomography (PET) in 16 patients with interstitial lung disease (ILD) by measuring the pulmonary transcapillary escape rate (PTCER) for transferrin labeled with gallium 68. In patients with active ILD, defined by lung biopsy or clinical criteria, mean PTCER was significantly greater than in normal subjects (118 +/- 46 versus 21 +/- 11 x 10(-4) min-1, respectively, p less than 0.05). Mean PTCER in patients with inactive ILD, in contrast, was not different from that in normal subjects (32 +/- 10 x 10(-4) min-1, p = NS). Thus, these data suggest that PET measurements of PTCER might serve as an index of disease activity in patients with ILD. PMID- 1596026 TI - Pulmonary oxalate deposition associated with Aspergillus niger infection. An oxidant hypothesis of toxicity. AB - Tissue injury by Aspergillus niger infection is associated with the deposition of calcium oxalate crystals. Oxalate is recognized to function as a ligand for numerous metal cations and will react with ferric ion to form a coordination complex. We describe oxalate deposition in the lung of a patient with A. niger infection and quantify surface-complexed Fe3+. Crystals collected from lung tissue demonstrated considerable concentrations of surface iron. In addition, we tested the hypothesis that this surface coordination of Fe3+ by oxalate is associated with increased in vitro oxidant generation. Calcium oxalate crystals (1.0 mg/ml) complexed all available Fe3+ from solutions of ferric chloride to concentrations of as much as 1.0 mM. Oxidant generation in both a chemical and a cellular system, measured as thiobarbituric-acid-reactive products of deoxyribose and chemiluminescence, respectively, increased with coordination of higher concentrations of inorganic iron. We conclude that calcium oxalate associated with A. niger infection complexes iron cations onto the crystalline surfaces and may generate oxidants at the solid-solution interface, which could result in tissue injury. PMID- 1596027 TI - Lack of bronchial hyperresponsiveness to methacholine and to isocapnic dry air hyperventilation in heart/lung and double-lung transplant recipients with normal lung histology. The Paris-Sud Lung Transplant Group. AB - To investigate whether survivors of heart/lung and double-lung transplantations have normal or increased nonspecific bronchial responsiveness, nine heart/lung and four double-lung transplant recipients with normal lung histology underwent methacholine challenge and voluntary isocapnic dry air hyperventilation (VIH) in a randomized order at a mean time of 14.8 +/- 12.1 months after surgery. Transplant recipients were compared with 10 normal subjects and 11 patients with mild asthma. Asthmatic patients had a mean provocative concentration of methacholine inducing a 20% fall (PC20) in FEV1 of 3.4 +/- 3.6 mg/ml (SD). Seventy seven percent of the transplant recipients and 70% of the normal subjects had PC20 superior to 32 mg/ml. The percentage fall from baseline FEV1 after VIH was 12.6 +/- 10.4% in asthmatic patients as compared with 1.9 +/- 2.9% in transplant recipients (p = 0.002) and 0.45 +/- 1.2% in normal subjects (p = 0.001). The decrease in FEV1 after VIH was similar in transplant recipients and normal subjects (p = 0.14). These results show that heart/lung or double-lung transplant recipients with normal lung histology have a normal response to nonspecific bronchial stimulation. PMID- 1596028 TI - NHLBI workshop summary. Environmental lung diseases. Relationship between acute inflammatory responses to air pollutants and chronic lung disease. PMID- 1596029 TI - Clinical utility of asbestos bodies in BAL fluid. PMID- 1596030 TI - Survival after emergency department versus operating room thoracotomy for penetrating cardiac injuries. AB - The authors undertook a 6-year retrospective review to assess their experience with penetrating cardiac injuries. Special emphasis was placed on identifying patients with and without tamponade and those requiring emergency department (ED) thoracotomy. Forty-eight patients were identified. Overall survival was 64.6 per cent. Thirty-three patients had tamponade, with 20 requiring ED thoracotomy. Fifteen patients did not have tamponade and two of these needed ED thoracotomy. Five patients who had ED thoracotomy were long-term survivors (22.7%). The remaining 26 patients, 13 with tamponade and 13 without, received operating room (OR) thoracotomy and all survived. The data shows that excellent results are possible with OR thoracotomy for penetrating cardiac injuries, with or without tamponade. However, results are not as good when ED thoracotomy is necessary. This may relate to the severity of the injury, the duration of tamponade, or the inability to control cardiac bleeding during thoracotomy in the ED setting. Even though survival is low with ED thoracotomy, it is high enough to continue to support its use in the deteriorating patient with a penetrating cardiac wound. PMID- 1596031 TI - Blunt trauma of the diaphragm: a 15-county, private hospital experience. AB - During a 6-year period, 52 patients with nonpenetrating trauma to the diaphragm were treated in eight acute care hospitals, serving a 15-county area of Michigan. Charts were reviewed to identify patterns of injury, treatment, and outcome. Preoperative diagnosis was made in 50 per cent of cases based on chest x-ray findings; the remainder were diagnosed intraoperatively. Clinical examination revealed respiratory distress, decreased breath sounds, or elevated hemidiaphragm in 81 per cent of patients. Forty-two per cent of patients sustained significant head injuries. Fractures were present in 75 per cent of patients. Major chest injury was found in 92 per cent. Intra-abdominal organs were herniated in 67 per cent of cases with the stomach being most common (54%). The spleen was the most commonly injured abdominal organ (60%). The left diaphragm was injured in 75 per cent of cases; 2 per cent were bilateral. The most common postoperative complication was pneumonia. Mortality in this series was 13 per cent, with no case being related to the diaphragmatic injury. The authors conclude that blunt injuries to the diaphragm in the multiply-injured patient present a clinical diagnostic challenge requiring a high index of suspicion. Optimal care requires a multi-disciplinary critical care team to manage the high incidence of associated central nervous system, orthopedic, and chest injuries and associated high mortality rates. PMID- 1596032 TI - Delayed splenic rupture: real or imaginary? AB - Although splenic injury is the most frequent abdominal injury resulting from blunt trauma, delayed splenic rupture is a rare event. From 1981 to 1990, 75 patients treated at St. Elizabeth Hospital Medical Center (Youngstown, OH) had blunt splenic injury. Splenic rupture was delayed in six of these patients (8%). More severe trauma, such as occurs with motor vehicle accidents, is more likely to lead to immediate rupture. Lesser trauma resulting from minor falls or fights is more likely to lead to delayed rupture. Subcapsular hematoma is the most common etiology for delayed splenic rupture. Although there is no reliable symptom or sign during the latent period, abdominal pain occurs almost uniformly and Kehr's sign is quite common. Peritoneal lavage and abdominal computerized axial tomography scan are accurate in diagnosing splenic rupture. Unfortunately, they are not always reliable in predicting delayed rupture. PMID- 1596034 TI - Injuries of the abdominal aorta from blunt trauma. AB - Blunt injuries of the abdominal aorta are rarely reported in the literature. If left undiagnosed, these injuries may have catastrophic consequences. Four patients with blunt abdominal aortic lesions, identified in the authors' trauma registry, are presented in this report, along with a discussion of the pertinent literature to illustrate clinical management techniques. The mechanisms of injury include motor vehicular crashes (most frequent) with or without seatbelt use, abdominal blows, falls, and abdominal crush injuries. The spectrum of aortic lesions ranges from simple contusion or intramural hematoma to intimal disruption, false aneurysm, or frank rupture. Aortography should be performed in all stable patients with suspected aortic injury. All central-medial retroperitoneal hematomas discovered at laparotomy for blunt trauma should be explored after proximal and distal control of the aorta is obtained. Strict adherence to these principles, maintenance of standard vascular technique, and aggressive, expeditious resuscitative evaluation may improve survival. PMID- 1596033 TI - The role of early tracheostomy in blunt, multiple organ trauma. AB - During a 9-year period, 101 patients sustaining blunt, multiple organ injury underwent tracheostomy. Group I consisted of 32 patients who underwent tracheostomy within the first 4 days of injury (early tracheostomy) and Group II comprised 69 patients who underwent tracheostomy more than 4 days after surgery (late tracheostomy). There was no statistical difference between the two groups in terms of age, Injury Severity Score, Glasgow Coma Score, and associated injuries. The mean time of mechanical ventilatory support was 6.0 +/- 3.4 days in Group I as compared to 20.6 +/- 12.2 days in Group II (P less than 0.001). Early weaning from the ventilator was accomplished in 32 (100%) patients who underwent early tracheostomy versus 43 (62%) of those who underwent late tracheostomy (P less than 0.001). Finally, the incidence of nosocomial pneumonias was also significantly less in patients undergoing early tracheostomy. There were three nonlethal complications associated with tracheostomy. The authors conclude that early tracheostomy helps in early weaning from the ventilator and reduces the incidence of nosocomial pneumonias and time of mechanical ventilatory support in patients with blunt, multiple organ injury. PMID- 1596036 TI - Cold-induced hypercoagulability in vitro: a trauma connection? AB - Injury severity score and hypothermia can lead to a high level of mortality when combined clinically. In acute trauma, the presence of a coagulopathy is difficult to treat and the aim is prevention. Aliquots of whole blood from healthy human volunteers (n = 9) were added to saline (control) and saline plus endotoxin (activated). The control and activated groups were divided and subjected to 60 minutes of normothermia (24 degrees C) or hypothermia (0 degrees C). The samples were returned to 37 degrees C; then the recalcification times were determined using fibrin formation and the viscous drag as the determining factors. The activated hypothermic group showed a decreased recalcification time of 345 (+/- 48.9) seconds compared to 405 (+/- 60.8) for the activated normothermic group (P less than 0.001). When the normothermic and hypothermic groups were compared without endotoxin added, the differences were not significant. The authors conclude that the effects of endotoxin on clotting time are worsened by hypothermia in vitro and act synergistically to possibly cause the coagulopathy seen in trauma patients. PMID- 1596035 TI - Argon beam coagulator hepatorrhaphy in potential donors. AB - Advances in medical technology have provided clinicians with the means to successfully treat life-threatening illnesses and injuries. For trauma surgeons, the acuteness and severity of thoracic and abdominal injuries may not allow time for complete, continuous neurologic examination, including computed tomography. The situation may arise in which urgent, major surgical intervention is necessary in a neurologically moribund patient. One such patient is presented herein; the Argon Beam Coagulator is used to repair a severe liver injury in this unstable trauma victim on whom a complete neurologic examination could not be performed. Cerebral death ensued and the repaired liver was successfully transplanted. PMID- 1596037 TI - Occult diaphragm injuries at celiotomy for left chest stab wounds. AB - No dependable test exists for diagnosis of diaphragmatic injury in asymptomatic patients with thoraco-abdominal stab wounds. Forty-one consecutive patients with anterior stab wounds of the lower left chest were treated in a 30-month period. In the 21 patients seen during the first 15 months, operations were reserved for those with peritoneal signs or continuing blood loss. Ten of these 21 patients (48%) required celiotomy; 2 patients (10%) had isolated diaphragm injuries and there was one negative celiotomy. Of the eleven patients who were not explored, 2 (18%) returned within 18 months after injury with an incarcerated diaphragmatic hernia. During the subsequent 15 months, the next 20 patients were managed by routine celiotomy in a prospective study. The admission systolic blood pressure and incidence of pneumothorax, celiotomy, diaphragm injury, isolated diaphragm injury, and unnecessary celiotomy in these two groups were compared. Ten patients in the prospective group (50%) were found to have isolated diaphragm injuries (P less than 0.005) and 7 (35%) had negative celiotomies (P less than 0.02). The true incidence of occult diaphragm injuries may be underestimated. In the prospectively studied group, the policy of routine celiotomy for anterior stab wounds of the lower left chest resulted in recognition and repair of a fivefold greater number of isolated diaphragm injuries. In the absence of a reliable, noninvasive test to diagnose penetration of the diaphragm, celiotomy should be considered in light of the risks of late strangulation. PMID- 1596038 TI - Is routine cervical spine radiographic evaluation indicated in patients with mandibular fractures? AB - Fractures of the mandible are commonly seen in most urban trauma centers. Over the past decade, the authors have seen a rise in these injuries secondary to an increase in drug and alcohol abuse, violent crime, and high-speed motor vehicle accidents. Several reports have described an association between mandibular fractures and cervical spine injuries and recommend routine cervical spine radiographs in all patients with mandibular injuries. These studies have failed to show a "cause and effect" relationship because of concomitant injuries found in these patients. This study reviews mandibular fractures and cervical spine injury retrospectively and prospectively over a 3-year period. The retrospective study included patients with isolated mandibular fractures who came to Cooper Hospital/University Medical Center Emergency Room in 1987. Thirty patients were identified, 18 of whom had cervical spine x rays. No patients had a significant radiologic or clinical cervical spine injury. The prospective study included all patients with mandibular fractures seen in the emergency room during 1988 and 1989. Seventy-three patients were identified, 44 of whom had mandibular and cervical spine radiographs. None had a significant radiologic or clinical cervical spine injury. The authors conclude that routine cervical spine x rays are costly and unnecessary. Also, any patient with a suspicion of concomitant cervical spine injury (i.e., patients with a loss of consciousness, multi-organ system injury, cervical pain or tenderness, or intoxication from alcohol use) should have cervical spine x rays, including anteroposterior, lateral, and open mouth odontoid views. PMID- 1596039 TI - Complete reconstruction of a traumatic disruption of the carotid bulb. AB - The management of a patient with complete carotid bulbar disruption and transection of the ipsilateral cervical vertebral artery is presented. Internal carotid arterial emboli resulted in acute hemiparesis and altered consciousness. Total reconstruction of the carotid bulb was accomplished with reversed saphenous vein. Complete neurologic recovery was achieved. This approach of composite venous reconstruction of the carotid artery may be considered for selected patients with this complex vascular injury. PMID- 1596040 TI - Management of post-traumatic acute renal failure with peritoneal dialysis. AB - To evaluate the efficacy of peritoneal dialysis (PD) in the management of post traumatic renal failure, the authors reviewed the courses of five critically injured patients treated with PD over an 18-month period. Each patient had a double-cuffed PD catheter inserted through a subcutaneous tunnel with PD initiated within 48 hours. The dialysis prescription was individualized for each patient with frequent exchanges performed using either a manual manifold system or a continuous cycling machine. Three of the five patients survived and none of the survivors required dialytic therapy at discharge. Duration of PD ranged from 10 to 57 days. Three patients required intermittent hemodialysis (HD) due to progressive azotemia and hyperkalemia. Two patients developed bacterial peritonitis and three patients developed hyperglycemia with PD continuing without interruption in each patient. When compared to HD, PD offers the advantages of better hemodynamic tolerance, no anticoagulation, no vascular access, and a reduced personnel requirement if continuous cyclic PD is used. PMID- 1596041 TI - Fast-growing cancer of the colon and rectum. AB - Recently, the existence of a flat, colorectal cancer has been proposed. This cancer is completely different in appearance from ordinary polyp cancer and is believed to invade deeply into the submucosa, even in its early stages. Its characteristics are quite different from cancers that follow the adenoma-cancer sequence, and it requires a greater search to detect. The authors observed four cases of fast-growing cancer that were relatively flat in appearance, contained no adenomatous component, and were invasive, even in their early stages. PMID- 1596042 TI - Mitral regurgitation in early myocardial infarction. Incidence, clinical detection, and prognostic implications. TIMI Study Group. AB - OBJECTIVE: To investigate mitral regurgitation occurring early in the course of acute myocardial infarction with respect to its incidence, the impact of infarct size and location, the accuracy of clinical detection, the contribution of global and regional left ventricular performance, and its influence on prognosis. DESIGN: Prospective observational study derived from patients entering Phase I of the Thrombolysis in Myocardial Infarction (TIMI) trial. SETTING: Multicenter trial involving 13 university-affiliated medical centers. PATIENTS: A total of 206 patients studied within 7 hours of symptom onset during their first myocardial infarction. MEASUREMENTS: Contrast left ventriculography was used to document mitral regurgitation. RESULTS: Mitral regurgitation was present in 27 patients (13%). Although the presence of regurgitation correlated with the site of infarction (20 of 27 had anterior infarctions) and the number of akinetic chords, it was not statistically related to the peak creatine kinase value or to left ventricular chamber size or filling pressure. A murmur of mitral regurgitation was heard in only 2 patients (1 incorrectly). The presence of early mitral regurgitation predicted cardiovascular mortality at 1 year by univariate (relative risk, 12.2; 95% Cl, 3.5 to 42; P less than 0.0001) and multivariate (relative risk, 7.5; Cl, 2.0 to 28.6; P = 0.0008) analyses. CONCLUSIONS: Mitral regurgitation in early myocardial infarction is generally clinically "silent," is more common in anterior infarction, is associated with regional dysfunction but not early ventricular dilation or peak enzyme release, and is an important predictor of cardiovascular mortality. PMID- 1596043 TI - Outcome of patients sustaining acute ischemic mitral regurgitation during myocardial infarction. AB - OBJECTIVE: To describe outcomes of patients sustaining an acute myocardial infarction complicated by mitral regurgitation managed with contemporary reperfusion therapies. DESIGN: Inception cohort case study. Long-term follow-up was obtained in 99% of all patients. SETTING: University referral center. PATIENTS: A series of 1,480 consecutive patients presenting between April 1986 and March 1989 who had emergency cardiac catheterization within 6 hours of infarction. Fifty patients were found to have moderately severe or severe mitral regurgitation. OUTCOME MEASURES: Mortality; follow-up cardiac catheterization in patients with regurgitation. RESULTS: Acute ischemic moderately severe to severe (3+ or 4+) mitral regurgitation was associated with a mortality of 24% at 30 days (95% CI, 12% to 36%), 42% at 6 months (CI, 28% to 56%), and 52% at 1 year (CI, 38% to 66%); multivariable analysis identified 3+ or 4+ mitral regurgitation as a possible independent predictor of mortality (P = 0.06). Patients with mitral regurgitation tended to be female, older, and to have cerebrovascular disease, diabetes, and preexisting symptomatic coronary artery disease. A physical examination did not identify 50% of patients with moderately severe to severe regurgitation. Acute reperfusion with thrombolysis or angioplasty did not reliably reverse valvular incompetence. In this observational study, the greatest in-hospital and 1-year mortalities were seen in patients reperfused with emergency balloon angioplasty, whereas patients managed medically or with coronary bypass surgery had lower mortalities. CONCLUSIONS: Moderately severe to severe (3+ or 4+) mitral regurgitation complicating acute myocardial infarction portends a grave prognosis. Acute reperfusion does not reduce mortality to levels experienced by patients with lesser degrees of mitral regurgitation nor does it reliably restore valvular competence. PMID- 1596045 TI - Primary ventricular tachycardia in acute myocardial infarction: clinical characteristics and mortality. The SPRINT Study Group. AB - OBJECTIVE: To examine the immediate and long-term clinical and prognostic significance of primary ventricular tachycardia, defined as tachycardia of ventricular origin occurring within 48 hours of acute myocardial infarction in patients without hemodynamic compromise (Killip class I). DESIGN: Prospective cohort study. SETTING: Intensive coronary care units in eight regional, referral, and university hospitals. PATIENTS: A total of 162 patients with primary ventricular tachycardia, both sustained and nonsustained (study group), and 2578 counterparts without ventricular tachycardia (reference group). MEASUREMENTS: In hospital rates of atrial fibrillation, atrioventricular block, congestive heart failure, cardiogenic shock, and cardiac arrest. In-hospital and 1-year follow-up rates of sudden death, nonsudden cardiac death, and noncardiac death. RESULTS: The study and reference groups had similar mortality (in-hospital, 6.8% and 9.6%, P greater than 0.2 and at 1 year after discharge, 3.7% and 5.4%, P greater than 0.2, respectively) and in-hospital complication rates (atrioventricular block, 13.0% and 9.7%, P greater than 0.2; cardiogenic shock, 3.7% and 3.0%, P greater than 0.2; cardiac arrest, 1.8% and 4.4%, P greater than 0.2, respectively). Patients with sustained ventricular tachycardia (28 patients) compared with those with nonsustained ventricular tachycardia (134 patients) had higher rates of polymorphic tachycardia (50% compared with 6%, P = 0.001), in-hospital total cardiac mortality (21% compared with 4%, P = 0.003) and sudden-death mortality (14% compared with 2%, P = 0.001); they also showed a trend toward a higher in hospital mortality than the reference group (21.4% compared with 9.6%, P = 0.15) but had no increased mortality 1 year after discharge (4.6% compared with 5.4%, P greater than 0.2). CONCLUSIONS: As a group, patients with primary ventricular tachycardia do not differ from counterparts without primary ventricular tachycardia in their in-hospital clinical course and 1-year prognosis. Primary sustained ventricular tachycardia is often polymorphic and carries worse in hospital prognosis than nonsustained tachycardia. However, it does not predict recurrent ventricular tachycardia or increased sudden-death rates during the next year. PMID- 1596044 TI - Treatment of human brucellosis with doxycycline plus rifampin or doxycycline plus streptomycin. A randomized, double-blind study. AB - OBJECTIVE: To compare the effectiveness of doxycycline-rifampin (DR) combination therapy with that of the classic doxycycline-streptomycin (DS) combination in patients with brucellosis. DESIGN: A randomized, double-blind study, with a mean follow-up of 15.7 months. SETTING: A 1000-bed teaching hospital in Barcelona, Spain. PATIENTS: Ninety-five patients (68 men and 27 women; mean age, 39 years) diagnosed with brucellosis on the basis of both clinical and serologic findings; 81 of these patients had blood cultures positive for Brucella melitensis. INTERVENTIONS: Forty-four patients received doxycycline, 100 mg every 12 hours, and rifampin, 15 mg/kg body weight per day in a single morning dose, for 45 days; 51 patients received the same dose of doxycycline for 45 days plus streptomycin, 1 g/d for 15 days. MAIN OUTCOME MEASURES: Therapeutic failure and relapse during the follow-up period. RESULTS: The mean time to defervescence was 4.2 days for the DR group and 3.2 days for the DS group (P greater than 0.2). The actuarial probability of therapeutic failure or relapse at 12 months of follow-up (Kaplan Meier) was 14.4% in the DR group and 5.9% in the DS group (difference, 8.5%; 95% Cl, -4.8% to 21.6%; P greater than 0.2). All three patients with spondylitis in the DR group failed therapy compared with one of four patients in the DS group. Excluding patients with spondylitis, the actuarial failure rate was 4.9% and 4.3% in the DR and DS groups, respectively, at 12 months of follow-up (difference, 0.6%; Cl, -8.1% to 9.4%; P greater than 0.2). CONCLUSIONS: Doxycycline-rifampin combination therapy for 45 days is as effective as the classic DS combination in most patients with brucellosis; however, DR therapy might be less effective in those patients with spondylitis. PMID- 1596046 TI - Cutaneous Pneumocystis carinii infection mimicking Kaposi sarcoma. PMID- 1596047 TI - Valve disease associated with ergot alkaloid use: echocardiographic and pathologic correlations. PMID- 1596048 TI - A bedside decision instrument to elicit a patient's preference concerning adjuvant chemotherapy for breast cancer. AB - The objective of this study was to develop an instrument to help clinicians inform patients with breast cancer of risks and benefits of adjuvant chemotherapy as derived from clinical trials and to help the informed patient decide whether she prefers treatment or no treatment. The instrument consists of a visual aid (called the decision board) and written material. It provides detailed information on a patient's choices (chemotherapy or no chemotherapy), outcomes (recurrence or not), probabilities of outcomes and their meaning, and quality of life associated with treatment choice and outcome. The validity and reliability of the instrument were evaluated in 30 healthy female volunteers. It was first administered using standard estimates of recurrence for node-negative breast cancer (15% risk of recurrence without treatment, which is reduced to 10% with chemotherapy). A preference for treatment (or no treatment) was then elicited. The validity was evaluated by changing the information provided on risks and benefits and determining whether the preference changed in a predictable manner. To test for reliability, the instrument was administered 2 weeks later. Seventeen women chose chemotherapy and 13 chose no chemotherapy. In the former group, 14 women (82%) switched preference when the magnitude of benefit was reduced, and 16 (94%) switched when the toxicity of treatment was increased. For those women who chose not to receive chemotherapy, 12 (92%) switched when the benefit was increased and 100% switched when toxicity was eliminated. The reliability was excellent (kappa = 0.86). The instrument has been used to elicit treatment preferences in 37 newly presenting patients with high-risk, node-negative breast cancer and has been found to be acceptable and helpful to the patient. PMID- 1596049 TI - The crisis in correctional health care: the impact of the National Drug Control Strategy on correctional health services. American College of Physicians, National Commission on Correctional Health Care, and American Correctional Health Services Association. PMID- 1596050 TI - Medical ethics and human rights violations: the Iraqi occupation of Kuwait and its aftermath. AB - Immediately after the liberation of Kuwait by a coalition of allied forces in March 1991, representatives of Physicians for Human Rights traveled to Kuwait and conducted an inquiry into human rights violations allegedly perpetrated by Iraqi forces. The inquiry focused on the abuses that were said to have occurred in health care institutions. Human rights abuses by the Iraqis in Kuwaiti hospitals were documented, but certain allegations proved to be unfounded. However, Kuwaiti abuses of those accused of collaborating with the Iraqi invaders, in particular Palestinian citizens of Kuwait, were also observed. The trip and inquiry generated questions about the scope and applicability of medical ethical principles to physicians in different cultures and in situations unlike those in which medicine is normally practiced. In light of the Kuwait experience, Physicians for Human Rights has drawn tentative conclusions about the universal nature of medical ethics. PMID- 1596051 TI - The laying on of hands. PMID- 1596052 TI - Estrogen therapy for osteoporosis--even in the elderly. PMID- 1596053 TI - Predictors of thromboembolism in atrial fibrillation. PMID- 1596054 TI - Polycystic kidney disease and angiotensin-converting enzyme inhibitors. PMID- 1596055 TI - Diagnosing Wilson disease. PMID- 1596056 TI - Diagnosing Wilson disease. PMID- 1596057 TI - Hepatitis E in a traveler to Bangladesh. PMID- 1596058 TI - Subgroup analyses. PMID- 1596059 TI - Thrombocytopenia as a clue to HIV. PMID- 1596060 TI - Acute quadriplegia in acromegaly. PMID- 1596061 TI - Cruise ship anisocoria. PMID- 1596062 TI - Surface area and tissue volume increases with differential expansion. AB - Increasing sophistication in generating soft tissue by tissue expansion has resulted in the evolution of differential expanders. These prostheses attempt to asymmetrically generate tissue for specific reconstruction, most commonly the breast. Using the pig model, differential expanders were placed in the rib area. A square grid was marked over the area, and the expander inflated. For each grid subunit, the surface area was calculated, the thickness measured, and the volume calculated. Subunits in the area of preferential expansion exhibited the greatest increase in surface area, however, these same subunits exhibited pronounced thinning of the tissue. The corresponding volume of these subunits was greater than that of nonexpanded subunits, but the increase was less than when comparing subunit surface area. All expanders were displaced superiorly during the course of inflation. These findings are of clinical significance in that the mastectomy scar and nipple reconstruction both are situated in the area of minimal thickness. Displacement of differential expanders must be anticipated so that the resultant inframammary fold will ultimately be symmetrical with the opposite side. PMID- 1596063 TI - The effect of tissue expansion on dermal fibroblast contraction. AB - Tissue expansion alters the function of skin cells. We studied the effects of expansion on the contractile function of dermal fibroblasts using an in vitro model, the fibroblast-populated collagen lattice (FPCL). Spherical expanders were placed dorsally in 30 Sprague-Dawley rats; one-half were serially inflated. One, 2, and 4 weeks later, 5 rats from each group were killed. Fibroblasts were cultured from dermis overlying the expanders and mixed with collagen, medium, and serum in petri dishes to form FPCL. Fibroblasts from 5 rats that had not undergone surgery were cultured to make control FPCL. Contraction was assessed by measuring the areas of the FPCL. At 48 hours, FPCL containing expanded fibroblasts had contracted significantly less than those containing unexpanded or control fibroblasts. Four weeks of expansion resulted in less contraction than 1 or 2 weeks. Tissue expansion inhibits the in vitro contractile function of dermal fibroblasts in the rat in a time-related fashion. PMID- 1596064 TI - Intraluminal lidocaine for analgesia after tissue expansion: a double-blind prospective trial in breast reconstruction. AB - A double-blind prospective placebo controlled trial of intraluminal lidocaine for pain relief after tissue expansion was performed in 18 women undergoing breast reconstruction. In contrast to others' claims of effective analgesia, no difference in the incidence of immediate or late pain after expansion could be demonstrated between 100 mg of lidocaine and placebo. The overall incidence of early pain was 8%. This was significantly less frequent than late pain, which occurred after 36% of all expansions. Postexpansion pain (early or late) was reported after nearly one-half of all expansions, most of which was ascribed to late pain. The incidence of pain did not significantly depend on the temporal progression of breast expansion, nor was there a difference in the incidence and prevalence of pain for patients undergoing unilateral versus simultaneous bilateral expansion. PMID- 1596066 TI - Umbilical reconstruction using a cone-shaped flap. AB - We have performed new umbilical reconstruction with good results in 9 patients using the procedure of forming a circular cone with a flap that is anchored onto the abdominal wall. Our procedure uses a single flap or brings two flaps together, to form a three-dimensional structure with a single or double suture line, so that the umbilicus will retain its depth over a long period of time. PMID- 1596065 TI - The use of high-frequency ultrasound for the dissection of small-diameter blood vessels and nerves. AB - The Cavitron ultrasonic surgical aspirator has been successfully used in general surgery and neurosurgery. We have explored its use in the dissection of small diameter blood vessels and nerves (1-2 mm) in a rat model. Our results seem to indicate that this technique may be useful in isolating blood vessels surrounded by fatty tissue without damage to the vessel itself. In this study, however, high frequency ultrasound did cause significant damage to peripheral nerves. PMID- 1596067 TI - The effect of hyperbaric oxygen on reperfusion of ischemic axial skin flaps: a laser Doppler analysis. AB - This study evaluates the microvascular reperfusion of ischemic skin flaps with and without acute hyperbaric oxygen (HBO) treatment. Thirty-two axial pattern epigastric skin flaps (3 x 6 cm) in male Wistar rats were subjected to 8 hours of global ischemia by pedicle clamp occlusion. The rats were divided into the following control and two experimental groups: Control (n = 12) with ischemia, no HBO; Group 1 (n = 11) with HBO treatment (three 1.75-hour dives, 2.5 absolute atm, 100% O2) during ischemia; and Group 2 (n = 9) with HBO treatment (two 1.75 hour dives) immediately after ischemia. Laser Doppler flows were recorded in two distal standardized flap locations at 0.5, 2, 4, and 18 hours after reperfusion in control rats and Group 1 rats and at 18 hours only in Group 2 rats, using a Med-Pacific 6000 laser Doppler unit. Mean distal flap laser Doppler flows (mV) were Control: 0.5 hours = 23.2 +/- 11.9, 2 hours = 52.8 +/- 27.3, 4 hours = 53.6 +/- 32.1, 18 hours = 40.2 +/- 36.2; Group 1: 0.5 hours = 71.8 +/- 30.9 (p less than 0.05 vs. control), 2 hours = 74.3 +/- 27.3, 4 hours = 67.4 +/- 20.6, 18 hours = 79.1 +/- 40.3 (p less than 0.05 vs. control); and Group 2: 18 hours = 90.3 +/- 47.9 (p less than 0.05 vs. control). It is concluded that acute HBO treatment of ischemic rat skin flaps improves distal microvascular perfusion as measured by laser Doppler flowmetry. This effect is observed for HBO treatment given either during or immediately after prolonged global ischemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596068 TI - The polyurethane foam covering the Meme breast prosthesis: a biomedical breakthrough or a biomaterial tar baby? AB - Because controversy continues to surround the implantation of the polyurethane foam-covered Meme breast prosthesis, in vitro experiments were conducted to determine: (1) whether the polyurethane foam contains extractable toluene diamine isomers (TDAs), and (2) whether the polyurethane foam releases TDAs on exposure to mild hydrolytic conditions. Results confirmed the presence of extractable TDAs and other impurities in the foam covering the unused Meme prosthesis, and that the concentrations of these impurities could be significantly reduced by washing the foam in a regular detergent. This washing step was omitted from the manufacturer's production process. Furthermore, on exposure to mild alkalis, the foam exhibited significant degradation, rapid fragmentation, loss of mechanical strength and physical integrity, as well as the release of additional TDAs. Because of the potential long-term risks associated with the release of TDAs in vivo, continued clinical use of the Meme prosthesis containing this particular type of foam appears questionable. PMID- 1596069 TI - Early tissue reaction to textured breast implant surfaces. AB - Capsular contracture around breast implants with smooth surfaces continues to be an unpredictable complication. Some surgeons believe that silicone implants covered with porous polyurethane foam have a lowered potential to contract. These textured implants are not as biocompatible as silicone. Recently, silicone implants with textured surfaces have been introduced with the hope that the incidence of unacceptable implant contracture will be reduced. Using a rat implant model, the tissue reaction to textured implant surfaces was assessed. The implant surfaces evaluated were Silastic II, Siltex, MISTI, Biocell, Silastic MSI, and Meme. Disks of each implant material were implanted under the dorsal skin of rats for a period of 28 days. Each implant with its surrounding tissue was excised, processed for histological analysis, and assessed for the tissue's response to the implant with particular emphasis on the formation of a continuous collagen capsule. The results indicated that the magnitude of surface texturing influenced the development of a complete capsule. Implant surfaces with a texture of less than 150 microns in height or depth (Silastic II, Siltex, and MISTI) resulted in the formation of complete capsules. An implant (Biocell) with irregular texturing (200-350 microns) produced an organized capsule over most of its surface with localized interruptions of the capsule at the sites of its deepest cavities. Implant surfaces with texturing that exceeded 350 microns in height or depth (Silastic MSI and Meme) resulted in inhibition of the formation of a continuous capsule during this 28-day study. PMID- 1596070 TI - Long-term patient satisfaction following reduction mammoplasty. AB - This study documents that reduction mammoplasty is a procedure with excellent long-term patient satisfaction. This has not been previously well documented. One hundred nine patients after reduction mammoplasty were surveyed by questionnaire. Results of the questionnaire indicated that the majority of patients were pleased with their breast size and breast shape. The majority had equal-sized breasts. Most were comfortable after surgery and had an easier time buying clothes. Ninety four percent of patients would have the procedure again. Multiple techniques for reduction mammoplasty were used and there were no significant differences with the exception of a change in nipple sensation. Nipple sensation was best preserved by using the inferior pedicle technique. PMID- 1596071 TI - Reconstruction of a major abdominal and chest wall defect using latissimus dorsi and extended deep inferior epigastric artery flap. AB - Large defects of the chest and abdominal cavity are a challenging reconstructive problem. We present reconstruction of a major chest and abdominal wall defect in a patient who had recurrent chondrosarcoma. The defect extended from just below the nipple almost to the umbilicus, and measured 28 x 30 cm. An "extended" latissimus dorsi muscle flap and extended deep inferior epigastric artery flap were used for reconstruction of the defect. A 1-year follow-up of the patient is presented. PMID- 1596072 TI - The superficial ulnar artery "trap" and the free forearm flap. AB - A superficial ulnar artery identified during the elevation of a free forearm flap is reported. This is the second case appearing in the English literature. The free forearm flap is increasingly popular among plastic surgeons, and it is therefore imperative that this anomaly be well recognized because inadvertent injury of this anomalous artery may devascularize the hand. In cadaver dissections, the incidence of this anomaly has been reported to be 3.1%. This variation is probably encountered in clinical practice more commonly, but it is not recognized. Identification of this anomalous artery is facilitated by elevating but not exsanguinating the forearm prior to harvesting the flap. PMID- 1596073 TI - A new method for correction of Stahl's ear. AB - Stahl's ear is characterized by a third crus, a flat helix, hypoplasia or total absence of the superior crus, and deformity of the scaphoid fossa. There are various methods for the correction of Stahl's ear, but the surgical correction of this deformity is more difficult than it appears. We recently devised a new surgical method of our own. During the past 4 years, we treated 5 patients with Stahl's ear with this procedure. Our procedure can be used in every kind of deformity of Stahl's ear and can get satisfactory results. PMID- 1596075 TI - A simple method for the classic tie-over dressing. AB - The classic tie-over dressing is commonly used in skin graft applications. A simple, quick, cheap, and effective method, using a stopper, is presented. The advantages of the stopper include ease of use, speed of application, and the ability to replace the device if early inspection of the graft is desired. PMID- 1596074 TI - Malignant melanoma with evidence of maturation arising from a giant congenital nevocellular nevus. AB - The association between melanoma and giant congenital nevocellular nevus has been well documented, although controversy still exists regarding the precise incidence. The following patient report illustrates the excision of malignant melanoma arising from a giant congenital nevocellular nevus in a 4-month-old infant. The child had malignant melanoma with deep dermal involvement diagnosed by incisional biopsy with positive margins. She underwent subsequent en bloc resection of the original biopsy site and nevus. The reexcision specimen showed no evidence of malignancy. No adjuvant chemotherapy was used. The child is disease free at 5 years. It is possible that very young children (infants) with melanoma arising in a giant congenital nevocellular nevus may have a good prognosis. PMID- 1596076 TI - An apparatus for standardizing skull radiography. AB - A simple apparatus for standardizing skull radiography is described. It produces symmetrical and reproducible radiographs in the posteroanterior view, Waters's view, Towne's view, and projections. PMID- 1596077 TI - Breast reconstruction with tissue expanders: obtaining an optimal result. AB - A large personal experience with breast reconstruction using tissue expanders (149 patients with Radovans, and more than 150 patients with Beckers), with many suboptimal results especially in the early learning stages, has brought about changes in approach offering a much higher probability of acceptable breasts. This report attempts to combine multiple factors useful in yielding such results. Areas addressed include immediate versus delayed reconstruction, selection of candidates, selection of expander type, appropriate placement of expander at a site minimizing the requirement for pocket modification, choosing the optimal size expander, importance of maximal overexpansion to yield a good submammary fold, and means of determining adequate overexpansion to match an unmodified contralateral breast and the risks inherent in overexpansion. Timing, interval, and length of maintenance of hyperexpansion are described along with deflation and timing of port removal. Both the skate and star techniques of nipple and areolar reconstruction in the hyperexpanded patient yield very acceptable results despite thinned skin and minimal subcutaneous tissue. Good, satisfactory, and suboptimal clinical results will be presented. In our experience, tissue expansion reconstruction offers distinct advantages in a large majority of patients with the proviso that patients are willing to accept the time required for hyperexpansion and the waiting period for deflation. PMID- 1596078 TI - Re: Perforation of the hard palate associated with cocaine abuse. PMID- 1596079 TI - Re: Team approach to total auricular reconstruction. PMID- 1596080 TI - Re: Carbon dioxide laser blepharoplasty--advantages and disadvantages. PMID- 1596081 TI - Functional reorganization of the brain in recovery from striatocapsular infarction in man. AB - We used positron emission tomography (PET) to study organizational changes in the functional anatomy of the brain in 10 patients following recovery from striatocapsular motor strokes. Comparisons of regional cerebral blood flow maps at rest between the patients and 10 normal subjects revealed significantly lower regional cerebral blood flow in the basal ganglia, thalamus, sensorimotor, insular, and dorsolateral prefrontal cortices, in the brainstem, and in the ipsilateral cerebellum in patients, contralateral to the side of the recovered hand. These deficits reflect the distribution of dysfunction caused by the ischemic lesion. Regional cerebral blood flow was significantly increased in the contralateral posterior cingulate and premotor cortices, and in the caudate nucleus ipsilateral to the recovered hand. During the performance of a motor task by the recovered hand, patients activated the contralateral cortical motor areas and ipsilateral cerebellum to the same extent as did normal subjects. However, activation was greater than in normal subjects in both insulae; in the inferior parietal (area 40), prefrontal and anterior cingulate cortices; in the ipsilateral premotor cortex and basal ganglia; and in the contralateral cerebellum. The pattern of cortical activation was also abnormal when the unaffected hand, contralateral to the hemiplegia, performed the task. We showed that bilateral activation of motor pathways and the recruitment of additional sensorimotor areas and of other specific cortical areas are associated with recovery from motor stroke due to striatocapsular infarction. Activation of anterior and posterior cingulate and prefrontal cortices suggests that selective attentional and intentional mechanisms may be important in the recovery process. Our findings suggest that there is considerable scope for functional plasticity in the adult human cerebral cortex. PMID- 1596082 TI - Memory disturbances following anterior communicating artery rupture. AB - Thirty patients with lesions due to the rupture and repair of an aneurysm of the anterior communicating artery were compared neuropsychologically with 27 patients with ruptures but no lesions and 30 normal control subjects. Patients with combined lesions in the basal forebrain and striatum (n = 5), or basal forebrain, striatum, and ventral frontal cortex (n = 7), had severe memory deficits, whereas patients with lesions in the basal forebrain (n = 7) or the striatum (n = 5) alone showed virtually no deficits. Patients with lesions of the basal forebrain and ventral frontal cortex together (n = 6) showed mild memory deficits. In contrast to the memory effects, emotional changes were most pronounced in patients with striate lesions alone. Basal forebrain or ventral frontal lesions ameliorated rather than aggravated the emotional effects of striate lesions. It is suggested that the basal forebrain and the striatum form links of different pathways related to mnemonic information processing. Both systems may be able to compensate for a dysfunction of the other, but lesions of both systems together may lead to strong and unrecoverable memory deficits. PMID- 1596083 TI - Vascular differentiation and glucose transporter expression in rat gliomas: effects of steroids. AB - The GLUT1 isoform of the glucose transporter is normally expressed at high levels in differentiated brain vessels that also express a permeability barrier. In contrast, malignant brain neoplasms have relatively undifferentiated vessels that are highly permeable, proliferate to high vascular densities, and often lose GLUT1 expression. Using the rat intracerebral 9L glioma model, we investigated whether dexamethasone-induced changes in permeability are associated with the appearance of other differentiated vascular properties. The percentage of vessels expressing immunohistochemically detectable GLUT1 (74.2 +/- 6.1%) and the tumor vessel density as assessed by laminin immunostaining (282 +/- 37 vessels/mm2) did not vary with control tumor size. Dexamethasone treatment resulted in an 83% reduction of vascular permeability to intravenous Evans blue, an increased percentage of vessels expressing GLUT1 (106.4 +/- 10.5%), lower vascular density (102 +/- 64 vessels/mm2), and smaller tumor size (control cross-sectional area, 17.0 +/- 3.4 mm2; treated, 4.6 +/- 1.0 mm2). Essentially all vessels became GLUT1 positive after dexamethasone treatment. Increased GLUT1 expression by glioma vessels in association with the appearance of other signs of differentiation (low vascular density, slow tumor growth) suggests that immunostaining for GLUT1 may identify neoplasms that are biologically less aggressive. PMID- 1596084 TI - Corticotropin-releasing hormone-induced seizures in infant rats originate in the amygdala. AB - The neuroanatomical substrate of seizures induced by picomolar amounts of corticotropin-releasing hormone in infant rats was investigated. Electrographic and behavioral phenomena were monitored in 42 rat pups aged 5 to 22 days. Rat pups carried bipolar electrodes implanted in subcortical limbic structures, as well as cortical electrodes and intracerebroventricular cannulae. The administration of corticotropin-releasing hormone produced age-specific seizures within minutes, which correlated with rhythmic amygdala discharges. Paroxysmal hippocampal and cortical discharges developed subsequently in some rats. Corticotropin-releasing hormone-induced electrographic and behavioral seizures originate in the amygdala. PMID- 1596085 TI - Paresis of contralateral smooth pursuit and normal vestibular smooth eye movements after unilateral brainstem lesions. AB - Pursuit and vestibular smooth eye movements were measured in patients with lesions of the caudal brainstem tegmentum identified by magnetic resonance imaging (MRI) and computed tomography (CT), with neuropathological correlation in 1 patient. Contralateral smooth pursuit gain was significantly lower than ipsilateral gain in each patient. Ipsilateral smooth pursuit gain was also subnormal in patients with unilateral pontine damage that caused slowing of ipsilateral saccades. Horizontal vestibulo-ocular reflex gain and phase were normal. These quantitative correlations indicate that lesions of the pontine tegmentum that paralyze ipsilateral saccades can spare the vestibulo-ocular reflex, and that smooth pursuit movement and the vestibulo-ocular reflex can be impaired independently by pontine or medullary lesions. In contrast to lesions at other sites, unilateral lesions of the pontine or medullary tegmentum impair contralateral smooth pursuit more than ipsilateral pursuit movements. These findings provide evidence that a double decussating pathway mediates smooth pursuit; the first decussation is from the pons to the cerebellum, and the second decussation is from the vestibular nucleus to the contralateral abducens nucleus. PMID- 1596086 TI - "Resetting" of postural tremors at the wrist with mechanical stretches in Parkinson's disease, essential tremor, and normal subjects mimicking tremor. AB - The response of postural wrist tremors to brief mechanical displacements was compared in two groups of patients, one with classical hereditary essential tremor (n = 18) and another with typical Parkinson's disease (n = 13). These groups were compared with an additional group of normal subjects mimicking wrist tremor (n = 9). The degree to which brief mechanical displacements of the wrist produced by torque pulses of three different sizes could modulate the timing of rhythmic electromyographic bursts in the forearm flexor muscles was quantified by deriving a resetting index, which could range between 0 (no phase resetting) and 1 (complete phase resetting). In all three groups of subjects studied, the resetting index varied significantly with the size of the mechanical perturbation and, in an inverse fashion, with the ongoing tremor amplitude. When due allowance for these factors was made, the difference in mean resetting indexes between the three groups of patients and subjects was reduced to the extent that no definitive statement could be made as to whether brief mechanical perturbations had more effect on essential tremor than parkinsonian tremor. The method is therefore unlikely to be useful in differentiating the common causes of postural wrist tremors. PMID- 1596087 TI - Oxidative metabolism in muscle mitochondria from patients with chronic alcoholism. AB - We investigated the effect of long-term ethanol intake on the function of skeletal muscle mitochondria from 30 human alcoholics. Mitochondrial studies included (1) oxidative phosphorylation, (2) the activity of the individual complexes of the respiratory chain, and (3) the cytochrome content. State 3 and state 4 oxidation rates with glutamate-malate, succinate, tetramethyl-p phenylenediamine-ascorbate, and acetylcarnitine-malate, the activity of the individual complexes of the respiratory chain, and the concentration of mitochondrial cytochromes were comparable in control subjects and alcoholic patients, and also in myopathic and nonmyopathic alcoholic patients. These results demonstrate that alcoholic myopathy is not associated with a deficiency in mitochondrial energy supply. PMID- 1596088 TI - Autoimmune inflammation of astrocyte transplants. AB - Astrocytes have been shown to be capable of serving as antigen-presenting cells and as targets for encephalitogenic cytotoxic T lymphocytes. The role of astrocytes in central nervous system (CNS) autoimmune inflammation is unclear. To study this further, we transplanted astrocyte aggregates into the anterior eye chamber of the mouse. The astrocytic nature of these transplants was confirmed by immunohistochemical detection of glial fibrillary acidic protein and the inability to detect oligodendrocyte or microglial markers. When mice bearing transplants were induced to develop experimental allergic encephalomyelitis by either passive or active protocols, the astrocyte transplants developed a perivascular inflammatory response similar to that seen in the host CNS during the course of the encephalomyelitis. The data suggest that astrocytes could serve as targets for the autoimmune attack of experimental allergic encephalomyelitis and support the possibility that the pathogenesis of this disease may involve an autoimmune reaction against a site other than the myelin sheath. PMID- 1596089 TI - Detection of coronavirus RNA and antigen in multiple sclerosis brain. AB - Epidemiological studies of patients with multiple sclerosis (MS) and animal model data support the hypothesis that viruses initiate the immunopathogenic events leading to demyelination in MS. There have been no reports, however, of consistent detection of viruses in MS central nervous system tissue. We probed MS and control brain with cDNA probes specific for human, murine, porcine, and bovine coronaviruses. We report the in situ hybridization detection of coronavirus RNA in 12 of 22 MS brain samples using cloned coronavirus cDNA probes. In addition, tissue was screened for coronavirus antigen by immunohistochemical methods; antigen was detected in two patients with rapidly progressive MS. Significant amounts of coronavirus antigen and RNA were observed in active demyelinating plaques from these two patients. These findings show that coronaviruses can infect the human central nervous system and raise the possibility that these viruses may contribute to the pathogenesis of MS in some patients. PMID- 1596090 TI - Prognostic value of cytogenetic analysis in human cerebral astrocytomas. AB - Cytogenetic analysis has become an important part of the diagnostic evaluation of most hematological neoplasms. However, there is limited information on the value of cytogenetic analysis in most solid tumors, including cerebral astrocytomas. This report summarizes a prospective cytogenetic study of 99 human cerebral astrocytomas, 16 mixed oligoastrocytomas, and 2 gliosarcomas. The cytogenetic procedure involved in situ culture and robotic harvesting techniques. Correlative clinical and survival data were available on all patients. We successfully cultured and obtained suitable metaphases in 107 of the 117 tumors. One or more chromosomally abnormal clones were observed in 72 tumors, and nonclonal or normal karyotypes were observed in 35 tumors. In a multivariate analysis, survival time was significantly better in patients whose tumors had normal or nonclonal karyotypes on cytogenetic analyses than in those whose tumors had clonal abnormalities (p = 0.0071). Our study demonstrates that cytogenetic analysis provides independent prognostic information in patients with cerebral astrocytomas. PMID- 1596091 TI - Recent progress toward understanding the molecular biology of von Recklinghausen neurofibromatosis. AB - The gene for von Recklinghausen neurofibromatosis (NF1) was recently identified by positional cloning and found to code for a large, ubiquitously expressed protein. This protein has both structural and functional similarity to a family of proteins with guanosine triphosphatase-activating properties, involved in the regulation of the protooncogene ras. One of the postulated functions of the NF1 gene product may relate to its ability to regulate ras-mediated cell proliferation. Selective pharmacotherapy directed at downregulating ras may be of benefit to patients with NF1. PMID- 1596092 TI - Ascorbate neurotoxicity in cortical cell culture. AB - Ascorbate (vitamin C) is believed to act as a neuromodulator that facilitates the release of neurotransmitters and inhibits neurotransmitter binding to receptors, including dopamine and N-methyl-D-aspartate receptors. Extracellular levels of ascorbate are known to reach the low millimolar range after ischemic brain injury. This study shows that treatment of cultured cortical neurons with micromolar to low millimolar ascorbate first inhibits total protein synthesis and then results in late neuronal death. Astrocytes are much less vulnerable to ascorbate than neurons. Ascorbate may exacerbate neuronal and glial damage after brain ischemia, and it may play a pathological role in other neurological diseases. PMID- 1596093 TI - Duplication of part of chromosome 17 is commonly associated with hereditary motor and sensory neuropathy type I (Charcot-Marie-Tooth disease type 1). AB - Hereditary motor and sensory neuropathy type I (HMSNI), also known as Charcot Marie-Tooth disease type 1 (CMT1), has been shown to be genetically heterogeneous. A major gene maps to chromosome 17 (CMT1A). A set of loci, D17S122, D17S125, and D17S124, show tight linkage to the CMT1A locus, and a duplication of D17S122 has been detected in some families. We show that the locus D17S122 is duplicated in affected individuals from 7 informative families with HMSNI. The duplication was demonstrated either by differences in hybridization densities between two bands of a restriction fragment length polymorphism or by the presence of all three alleles. No normal individual had the duplication. A single recombinant exists between the MspI polymorphism of D17S122 and the duplicated band, suggesting that the duplication is of considerable size. Patients with HMSN type II do not show the duplication. These findings will have considerable impact on the diagnosis of chronic demyelinating neuropathies, in patients with or without similarly affected relatives. PMID- 1596094 TI - Charles Loomis Dana. PMID- 1596095 TI - Naltrexone and Tourette's syndrome. PMID- 1596096 TI - Treatment of Guillain-Barre syndrome with protein-A immunoadsorption: report of two cases. PMID- 1596097 TI - Normal aging of the nervous system. PMID- 1596098 TI - DDAVP in the management of nocturia in multiple sclerosis. PMID- 1596099 TI - Cancer incidence following chlorophenol exposure in a community in southern Finland. AB - Chlorophenols have contaminated the drinking water system and the local lake in the village of Jarvela in southern Finland. Local geology, ground water streams, and chemical analyses incriminated a local sawmill as the only plausible source of exposure. Cancer incidence in the municipality of Karkola (half of the population lives in Jarvela), compared with the rest of the local health-care district and with the greater cancer control region, indicated an excess of soft tissue sarcomas and non-Hodgkin's lymphomas. A case-control study, which focused on cancers of the colon, bladder and soft tissues, lymphomas, and leukemia, demonstrated a significantly elevated risk ratio for non-Hodgkin's lymphomas among persons who consumed fish from the local lake, which was contaminated with chlorophenols. Probable exposure to chlorophenol-contaminated drinking water played a role in the increased incidence of non-Hodgkin's lymphomas and possibly was a factor in the development of soft-tissue sarcoma. PMID- 1596100 TI - Kinetics of mercury in blood and urine after brief occupational exposure. AB - The decrease in mercury (Hg) levels in whole blood (B), plasma (P), erythrocytes (Ery), and urine (U) was investigated in nine men after 3 d of intense (greater than 100 micrograms/m3) exposure to metallic Hg vapor. In a model in which common half-times for all subjects were used, the best fit for B-Hg was obtained with half-times of 3.1 d for a fast phase and 18 d for a slow phase. P-Hg seemed to decay more rapidly than Ery-Hg. Peak U-Hg (morning, creatinine-corrected samples) was not observed until 2-3 wk after exposure. Thereafter, the median half-time was 40 d (assuming individual one-compartment models). In a model for which common half-times were used, the point estimates were 59 d for a one-compartment model and 28 and 141 d for a two-compartment model. The fractions of the fast phases (i.e., two-compartment models with common half-times) were 80% for B-Hg and 84% for U-Hg. PMID- 1596101 TI - Impact of maternal seafood diet on fetal exposure to mercury, selenium, and lead. AB - Umbilical cord blood from 1,023 consecutive births in the Faroe Islands showed a median blood-mercury concentration of 121 nmol/l (24.2 micrograms/l); 250 of those samples (25.1%) had blood-mercury concentrations that exceeded 200 nmol/l (40 micrograms/l). Maternal hair mercury concentrations showed a median of 22.5 nmol/g (4.5 micrograms/g), and 130 samples (12.7%) contained concentrations that exceeded 50 nmol/g (10 micrograms/g). Frequent ingestion of whale meat dinners during pregnancy and, to a much lesser degree, frequent consumption of fish, and increased parity or age were associated with high mercury concentrations in cord blood and hair. Blood-mercury levels were slightly lower if the mother had occasionally ingested alcoholic beverages. Mercury in blood correlated moderately with blood selenium (median, 1.40 mumol/l). Increased selenium concentrations were associated with intake of whale meat, alcohol abstention, delivery after term, and high parity. Lead in cord blood was low (median, 82 nmol/l), particularly if the mothers had frequently had fish for dinner and had abstained from smoking. PMID- 1596102 TI - Significance of urinary cadmium concentration in a Japanese population environmentally exposed to cadmium. AB - An epidemiological study was performed on 1,815 cadmium-exposed and 240 nonexposed inhabitants of the Kakehashi River basin in Ishikawa, Japan. The significance of urinary cadmium concentration as an indicator of internal dose in a general environment polluted by cadmium was investigated. The mean urinary cadmium concentration (Cd-U) increased in a dose-related manner when the subjects were classified according to the average cadmium concentration in their village rice and according to their period of residence in the polluted area. As total cadmium intake increased, Cd-U also increased, and strong correlations were found (r = .93 in men and r = .88 in women). Therefore, it was concluded that, on a group basis, Cd-U is a useful indicator of the internal dose of environmental cadmium exposure. PMID- 1596103 TI - Determinants of blood lead concentrations to age 5 years in a birth cohort study of children living in the lead smelting city of Port Pirie and surrounding areas. AB - Sources of variation and some principal determinants of blood lead concentration (PbB) were investigated in a cohort of children, followed to age 5 y, who were born near a lead smelter in Port Pirie, South Australia. The child's age and place of residence were the two variables most strongly predictive of PbB. A sharp increase in PbB occurred between 6 and 15 mo of age and was followed by a peak concentration that occurred at approximately 2 y of age, after which PbB steadily and consistently declined. Irrespective of age, the PbBs in children who lived in Port Pirie were significantly higher than levels identified in children who resided outside the city. There was no significant difference in PbB between boys and girls. Elevated PbB at each specific age was associated mainly with increased lead concentrations in the topsoil of the local residential area, employment of the father in the lead industry, parental smoking, and behaviors likely to cause ingestion of dirt. Blood samples taken from children at certain ages and during the warmer months contained more lead than samples obtained during the cooler months. The effects of these determinants on PbB during early childhood were basically consistent in both single and multivariable analyses. PMID- 1596104 TI - Daily mortality and PM10 pollution in Utah Valley. AB - The association between daily mortality and respirable particulate pollution (PM10) in Utah County was assessed from April 1985 through December 1989. Poisson regression analysis was used to regress daily death counts on PM10 pollution levels, controlling for variability in the weather. A significant positive association between nonaccidental mortality and PM10 pollution was observed. The strongest association was with 5-d moving average PM10 levels, including the concurrent day and the preceding 4 d. An increase in 5-d moving average PM10 levels, equal to 100 micrograms/m3, was associated with an estimated increase in deaths per day equal to 16%. The association with mortality and PM10 was largest for respiratory disease deaths, next largest for cardiovascular deaths, and smallest for all other deaths. Mean PM10 concentrations during the study period equaled 47 micrograms/m3. The maximum 24-h and 5-d moving average PM10 levels equaled 365 and 297 micrograms/m3, respectively. Relatively low levels of sulfur dioxide, aerosol acidity, and ozone suggested an independent association between mortality and PM10. The relative risk of death increased monotonically with PM10, and the relationship was observed at PM10 levels that were well below the current National Ambient Air Quality Standard of 150 micrograms/m3. PMID- 1596105 TI - A longitudinal study of lung function in jute processing workers. AB - A 5-y follow-up study of pulmonary function was conducted in 1982 and in 1987 for 50 current and retired jute-processing workers who had been employed for more than 10 y in a jute mill in China. Control subjects, who had no history of dust or gas exposure, were selected from a paper-packing plant in the same city. Forced expiratory maneuvers were conducted in the same manner in both 1982 and 1987. The jute workers' pulmonary functions, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow (FEF25-75%), were more compromised than were pulmonary functions in the controls for the same 5-y period; however, only the increased incidence of abnormal FEV1.0s in jute workers was statistically significant. Male jute workers had significantly higher annual decrements of FVC, FEV1.0, and FEF25-75% than did control workers. Regression analysis indicated that in 1987, predicted values of FEV1.0 and FEF25 75% for the jute workers were related to years of employment. Our results suggest that long-term exposure to jute dust could produce chronic loss of lung function. PMID- 1596106 TI - Nasal inhalation challenge studies with sidestream tobacco smoke. AB - Environmental tobacco smoke (ETS) exposure is associated with rhinitis symptoms (i.e., runny nose and congestion) in some people. In an effort to better understand these symptoms, we recruited 18 historically ETS-sensitive subjects from the community and exposed them for 15 min to clean air and for 15 min to sidestream tobacco smoke (STS, 45 ppm carbon monoxide). Symptoms were recorded (0 = absent, 5 = severe), and posterior rhinomanometry was performed. There were significant changes in rhinitis symptoms (1.3 +/- 0.4 pre- versus 6.1 +/- 0.5 post-STS, p less than .05); nasal airway resistance (2.86 +/- 0.2 pre- versus 4.49 +/- 0.6 post-STS, p less than .05), and maximum inspiratory flow (2.74 +/- 0.3 pre- versus 2.14 +/- 0.3 post-STS, p less than .05). A spectrum of individual responsiveness to ETS was observed, and nasal resistance increased from 0% to 265%. Increased nasal resistance occurred primarily at the upstream or flow limiting segment of the nasal airway. PMID- 1596107 TI - Ongoing research in occupational health and environmental epidemiology in developing countries. AB - Research in occupational health and environmental epidemiology can play an important role in furthering our understanding of occupational and environmental health problems. Research guides us in the recognition, management, and prevention of health problems. However, in developing countries, where rates of occupational and environmental illnesses and injuries are higher and where these problems are often more severe than in developed countries, research capabilities are less developed. In mid-1990, a project was undertaken to (a) document ongoing research in occupational health and environmental epidemiology in developing countries, (b) facilitate the exchange of information among researchers in this field, (c) stimulate research, and (d) avoid unnecessary duplication among researchers in this field. A questionnaire was mailed, the purpose of which was to learn the current status of research in developing countries and to develop a directory of such ongoing research. The questionnaire was sent to 1,528 individuals. Of the 500 research projects identified, 77% were investigating chemical hazards; 26%, physical hazards; 10%, biological hazards; and 10%, psychosocial hazards (some projects addressed multiple hazards). The chemical hazards studied most frequently were dusts, pesticides, and lead. The greatest number of research projects were identified in China, India, Brazil, Korea, and Thailand. Most projects were descriptive or cross-sectional epidemiologic studies or industrial hygiene or exposure-assessment studies. The World Health Organization has published a directory of the specific research projects that were identified in this survey. PMID- 1596108 TI - Residential mobility during pregnancy for mothers of infants with or without congenital cardiac anomalies: a reprint. AB - Maternal residence at time of delivery is sometimes used as a proxy for residence during early pregnancy to estimate environmental exposures. Residential addresses during time of conception through the first trimester were obtained from mothers of 152 infants with congenital cardiac anomalies and 175 controls, and they were compared with the addresses at delivery abstracted from birth certificates. An estimated 24.8% (95% CI = 20.3, 29.9) of women moved between the time of conception and delivery, and the percentage of cases and controls who moved was similar. Use of address at time of delivery may reduce the likelihood of finding an association between a congenital malformation and a maternal environmental exposure. PMID- 1596109 TI - Milieu therapy for short stay units: a transformed practice theory. AB - Milieu therapy is an interdisciplinary treatment approach widely applied in psychiatric settings. Current short stay inpatient trends indicate a need to adapt the approach so that it remains useful for nursing practice in those settings. This report presents basic historical milieu concepts with their relationships to patient outcome; current short stay patient needs, outcomes, and nursing actions are developed and linked with the historical concepts. The resulting transformed theory can be seen as an adaptation of the classic approach, tailored to short stay settings, with short-term goals and a clarified role for the nurse in the milieu. PMID- 1596110 TI - Methodological concerns in evaluating psychiatric nursing care modalities and a proposed standard group protocol format for nurse-led groups. AB - The importance of detailing therapeutic effort and its outcome cannot be underestimated. The need to document outcomes has been re-emphasized in recent psychiatric mental health literature; however, the methodology for addressing threats to validity is well established. This article identifies the problems and issues related to a systematic evaluation of a therapeutic group intervention in an inpatient setting, specifically threats to validity, and describes the processes used in planning and implementing a standard group protocol format. The findings of this project depicting problems in the clarity and precision of documenting nursing practice are believed to be typical and generalizable. However, problems related to clarity and precision have not been addressed in the nursing literature. For a number of reasons, nursing staff members have not been sensitized to the importance of describing their practices in sufficient detail to allow others to replicate these practices. And yet, adequate evaluations of nursing efforts, particularly programmatic initiatives, require systematic testing with repeated trials. Although no description can describe in absolute terms what occurred, clear and precise descriptions of an intervention provide the foundation for valid conclusions about the effort. A detailed standard group protocol format provides a basis for establishing internal validity in subsequent quasi-experimental research designs as well as program evaluation studies. PMID- 1596111 TI - Interagency psychiatric consultation liaison nursing peer review and peer board: quality assurance and empowerment. AB - This article describes the implementation of an interagency peer review group and formal review board for psychiatric consultation liaison nurses (PCLN) practicing in affiliated institutions. Peer group members enhance their skill levels, assure quality standards of practice, and implement system changes through peer collaboration and member feedback. The model assures quality PCLN practice, fosters member resilience, creates a counterbalance for PCLN role isolation, and provides professional empowerment. The authors also disclose the peer group members' struggle and resolution to implement the mandated task of the annual performance review through the process of the PCLN formal peer review board. PMID- 1596112 TI - The dynamics of laughter. AB - The benefits of humor have been accepted throughout human history. Humor is widely accepted for its positive physiological and psychological effects in a variety of situations. The psychiatric literature purports humor as an effective tool in psychiatric illness and psychotherapy. The benefits of humor in business, management, and education are also being described because the right perspective facilitates problem solving both interpersonally and in a group setting, and humor puts people at ease, promoting expression and the exchange of ideas. In the nursing literature, humor and laughter are increasingly presented as an approach that can assist the nurse in meeting health-related goals and objectives. Not only can humor benefit the patient, but the use of humor can facilitate effective management of staff and others encountered in the health care setting. Humor also has negative functions. Although the nursing literature on humor identifies that there are some situations in which humor is contraindicated, little attention is given to the problem created for the nurse when others, i.e., patients or family members, fellow staff members, or physicians, laugh inappropriately. This article discusses the assessment of laughter. Benefits of laughter and humor are described. The causes of inappropriate laughter are outlined, and the dynamics of inappropriate laughter are considered. Finally, implications for nursing practice are discussed. PMID- 1596113 TI - Nursing research at NIMH: an update. PMID- 1596114 TI - The flipper. PMID- 1596115 TI - Prescriptive authority for psychiatric clinical specialists: framing the issues. AB - Prescriptive authority is of increasing interest to advanced practice psychiatric nurses. A growing number of states have passed legislation authorizing prescriptive authority for this specialty group. In preparing for an orderly assimilation of this intervention into psychiatric nursing's existing scope of practice, it is important to understand some of the unique issues facing the specialty. This report provides an overview of prescriptive practice legislation, legal issues associated with prescribing psychotropic medication to psychiatric clientele, and prescriptive activities common to the specialty practice of psychiatry. Issues for the specialty of psychiatric nursing are reviewed and recommendations are offered for an action plan. PMID- 1596116 TI - Solution-oriented therapy and Rogerian nursing science: an integrated approach. AB - This article describes an approach to counseling and therapy that integrates concepts from Martha Rogers' science of unitary human beings with a contemporary, strategic school of therapy called brief, solution-oriented therapy. The purpose of this discussion is to stimulate clinicians' interest in solving human problems by creative use of client strengths and patterns of living. A theoretical discussion of Rogers and of solution-oriented therapy is followed by many examples of clinical application from the author's practice. Resources for further learning are recommended. PMID- 1596117 TI - Functional status of older persons with chronic mental illness living in a home setting. AB - The purpose of the study was to determine the functional status of older persons with chronic mental illness. One hundred subjects living in their homes were interviewed in face-to-face interviews using the Older Adult Resources Survey (OARS) to determine functioning in five areas: social, economic, mental, physical, and activities of daily living. Pearson product moment correlation showed significant relationships among all functional scores. Twenty-nine percent of the total sample had social relationships of poor quality. Thirty-five percent of subjects had severe economic impairment. The majority (53%) of subjects had psychiatric symptoms. The most common psychiatric diagnosis was depression (42%), followed by schizophrenia (22%), and bipolar illness (13%). Twenty-nine percent of subjects had a serious medical problem that required medical treatment. Cardiovascular diseases were the most frequently reported (92%), followed by arthritis (45%) and urinary tract disorders (19%). All subjects perceived that their physical health had deteriorated over the 5 years. Polypharmacy and drug misuse were common among the sample. A mean of four prescribed drugs was taken daily over the past month. Psychotropic (83%), antihypertensive (32%), and cardiac (20%) medications were the most frequently prescribed drugs. Twenty-five percent of the sample regularly required assistance with at least four activities of daily living. PMID- 1596118 TI - Disruptive behaviors of a cognitively impaired nursing home resident. AB - The descriptive case study of a 71-year-old man with Primary Degenerative Alzheimer's Dementia identifies and describes specific disruptive behaviors exhibited by a demented, disruptive nursing home resident and the biopsychosocial characteristics of these behaviors. The Disruptive Behavior Scale (Beck, Baldwin, Heithoff, & Cuffel, 1990) measured disruptive behaviors. Data collected included chart review, interviews, testing, and observation. The majority of observed disruptive behaviors fell under four categories: (1) walks aimlessly, (2) makes repetitive noises, (3) uses obscene/profane language, and (4) makes repetitive movements. Staff members and chart notes reported the same categories, except for "makes repetitive noises." All aggressive behavior toward the staff occurred during assistance with activities of daily living (ADLs). PMID- 1596119 TI - Penetrating cardiac trauma: management strategy based on 129 surgical emergencies over 2 years. AB - Between 1986 and 1988, 129 patients with stab wounds to the heart were referred from the emergency room of our institution for a thoracic surgical procedure. Multiple entrance wounds of the heart were present in 12 patients, and through and-through stab wounds were encountered in another 10. The overall hospital mortality rate was 8.5% (11/129), which includes a 54% mortality rate for the 13 patients undergoing emergency room thoracotomy. These patients were pulseless and unconscious either on arrival (n = 8) or soon thereafter (n = 5). Cardiopulmonary bypass was not used during the primary operation, although 7 patients underwent subsequent intracardiac repair with bypass without hospital mortality. Important aspects of our preoperative management strategy include: (1) aggressive transfusion to improve the central venous pressure/intrapericardial pressure gradient; (2) rapid drainage of the pleural and pericardial spaces to reduce intrapericardial pressure; (3) empirical partial correction of metabolic acidosis with sodium bicarbonate; and (4) emergency operation without unnecessary cardiac imaging. Patients suspected of having penetrating cardiac trauma and cardiac tamponade are best managed by aggressive primary intervention and immediate operation. PMID- 1596120 TI - Long-term results after tetracycline pleurodesis in spontaneous pneumothorax. AB - From 1979 to 1988 483 patients were admitted with primary spontaneous pneumothorax. All patients underwent thoracoscopy to identify the cause of pneumothorax. Chemical pleurodesis with instillation of tetracycline was performed if cysts less than 2 cm in diameter were found. If larger cysts were identified the patient underwent thoracotomy. In 93 patients with cysts larger than 2 cm the recurrence rate after thoracotomy was 4%. In 390 patients treated with intrapleural instillation of tetracycline, the recurrence rate was 16%. Fifty percent of the recurrences occurred within 30 days. The cause of recurrence in 42 patients (69%) was cysts missed at the initial thoracoscopy. This study has demonstrated that thoracoscopy is a reliable and safe method for selection of patients for chemical pleurodesis. It is, however, necessary that the thoracoscopy is meticulous to avoid recurrence from missed cysts. PMID- 1596121 TI - Influence of alprostadil on pulmonary dysfunction after a cardiac operation. AB - To test the effects of alprostadil on pulmonary dysfunction after cardiac operations, we studied 24 male patients undergoing aortocoronary bypass. Twelve were given an intravenous infusion of alprostadil (synthetic prostaglandin E1), 20 ng.kg-1.min-1, in a double-blind manner during operation; the other 12 were controls. Duration of artificial respirator use and frequent blood gas analyses were used to assess postoperative pulmonary function. Use of the artificial respirator postoperatively was significantly lower in the prostaglandin group (mean time. 5.25 +/- 1.81 hours) compared with the controls (mean time, 8.34 +/- 4.35 hours) (p = 0.047). The proportion of patients with hypercapnia and with hypoxia determined every 4 hours for the first 24 hours after extubation was significantly lower in the prostaglandin group compared with the controls (p less than 0.0001). These results indicate that synthetic prostaglandin E1 may play a role in protecting lung tissue during extracorporeal circulation. PMID- 1596122 TI - Breast development and areola sensitivity after submammary skin incision for median sternotomy. AB - Vertical incision for median sternotomy may result in unsightly scars. Therefore we have used a horizontal approach in women since the early 1980s. Of 36 women, 27 came for a follow-up examination. A tendency toward scar hypertrophy was found medially in 7 women. Four breast-fed their child after operation. Reduced areola sensitivity occurred in only 9 women. Horizontal submammary skin incision resulted in cosmetically acceptable scar formation and did not harm breast development and lactation. PMID- 1596123 TI - Skeletal muscle ventricles with improved thromboresistance: 28 weeks in circulation. AB - Skeletal muscle ventricles (SMVs) were constructed from the left latissimus dorsi in 22 mongrel dogs. The configuration of these SMVs was different from those previously reported. The animals were divided into two groups: group A (n = 11) SMVs rested for 10 weeks after construction; group B (n = 11) SMVs rested for 18 weeks. At the end of the delay period, SMVs were tested in vivo with a mock circulation device. The SMVs in group B developed stroke work greater than those in group A. After acute testing, SMVs (n = 12) were connected to the descending thoracic aorta and stimulated to contract during diastole. Aortic diastolic counterpulsation was achieved in all dogs, with 9 animals surviving from 1 to beyond 28 weeks. In all of the dogs surviving 1 week or more, the SMVs remained free of thrombus. Aspirin was used as the only antithrombotic agent. Skeletal muscle ventricles in this study were able to develop stroke work similar to that previously reported, intermediate between that of the right and left ventricular stroke work, with a significantly decreased incidence of thromboembolism. PMID- 1596124 TI - Contraction and relaxation of human internal mammary artery after intraluminal administration of papaverine. AB - The internal mammary artery has become the conduit of choice for coronary artery bypass grafting. Intraluminal papaverine treatment during operation reduces vasospasm and facilitates anastomosis. However, it has been suggested that papaverine may cause intimal damage, and accordingly we have investigated endothelial damage by comparing the responsiveness of internal mammary arteries before and after intraluminal exposure to papaverine (15 mg/mL). Control and papaverine-treated segments of internal mammary artery were obtained from 13 patients undergoing coronary artery bypass grafting and mounted as ring preparations in an organ bath. Cumulative dose contractions to noradrenaline were performed, and the dose producing a half maximal response was determined. Relaxation studies of submaximally contracted arteries were performed using the endothelium-dependent vasodilators acetylcholine and bradykinin and the endothelium-independent vasodilator sodium nitroprusside. In the human internal mammary artery the use of intraluminal papaverine increased the lumen size by 20% (p less than 0.05), and the contractions elicited by noradrenaline were significantly less in the papaverine group than in the control group (p less than 0.05). Endothelium-dependent relaxation to acetylcholine or bradykinin was not affected by papaverine treatment. Endothelium-independent relaxation was the same in both groups, with almost 100% relaxation achieved by sodium nitroprusside. These results indicate that intraluminal papaverine treatment during coronary artery bypass grafting causes a reduction of smooth muscle contraction and does not impair endothelium-dependent relaxation. PMID- 1596125 TI - Early and late outcome after diagnostic thoracoscopy and talc pleurodesis. AB - Although thoracoscopy is now recognized to be of both diagnostic and therapeutic value, the risks of this procedure have not been fully addressed. We retrospectively reviewed our experience with 100 patients who underwent 110 thoracoscopies during the period January 1989 to February 1991. Sixty-five men and 35 women (ratio of 1.9:1) underwent thoracoscopy using general anesthesia and intubation with a double-lumen endotracheal tube. The mean age was 64.2 +/- 11.6 years (range, 13 to 85 years). The diagnosis was established in 48 (85.7%) of the 56 patients with undiagnosed pleural effusions. Forty-four patients were referred for therapeutic thoracoscopic talc pleurodesis. Pleurodesis was successful in 42 patients (95.5%). Four patients (4%) had five postoperative complications (two bronchopleural fistulas, two chest infections, and one arrhythmia). Five patients (5%) died after thoracoscopy; mean age was 67.8 +/- 8.1 years (range, 55 to 77 years). The causes of death were cardiac arrest in 2, respiratory failure in 1, and malignant cachexia in 2. The findings of this study confirm that thoracoscopy can achieve high rates of diagnostic and therapeutic success but is not without attendant mortality in a high-risk patient population. PMID- 1596127 TI - Twenty-four-hour heparin-free veno-right ventricular ECMO: an experimental study. AB - Platelets and coagulation factors were studied during 24-hour heparin-free veno right ventricular extracorporeal membrane oxygenation (ECMO) in 6 healthy pigs. An endpoint attached and covalently bonded heparin-coated ECMO system was used in these experiments. The veno-right ventricular ECMO supplied the total lung function of the animals, and after 24 hours, all the animals were successfully weaned from ECMO. Lung function and central hemodynamics were not affected by the procedure. Because all the animals showed a significant reduction in plasma volume, the concentration of measured coagulation variables was corrected both for plasma volume changes and for hemodilution. The platelet count and the plasma free hemoglobin level were not significantly altered by ECMO. Similarly, the prothrombin complex, antithrombin, thrombin-antithrombin complex, factor XII, and the urinary excretion of 2,3-dinor-thromboxane B2 were not significantly altered. Fibrinogen and fibrin monomer increased significantly, whereas von Willebrand factor was significantly decreased after ECMO. In summary, 24-hour heparin-free veno-right ventricular total extracorporeal lung assistance does not affect the platelets and the coagulation system significantly in healthy juvenile pigs. PMID- 1596126 TI - Completion pneumonectomy after bronchial sleeve resection: incidence, indications, and results. AB - During the years 1960 through 1989, 145 patients underwent sleeve lobectomy or sleeve resection of a main bronchus. Completion pneumonectomy was performed in 19 patients (13.1%). Indications were bronchostenosis without malignancy in 10 patients, positive resection margins in 3, recurrent tumor in 5, and anastomotic dehiscence in 1. Mean age at sleeve operation was 59.3 years. In 18 patients the histology was squamous cell carcinoma and in 1 patient, carcinoid tumor. The mean interval between sleeve resection and completion pneumonectomy was 5.7 months (range, 3 to 16 months) for the patients with stenosis and 6.6 months (range, 1 to 17 months) for the others. There were 3 operative deaths (15.8%). The mean follow-up was 53.2 months. Five-year and 10-year survival rates after completion pneumonectomy for the patients with stenosis were 54% and 41%, respectively, and for the others, 52% and 52%. PMID- 1596128 TI - Multivariate analysis of postoperative complications after esophageal resection. AB - To determine the contributing factors for eight postoperative complications after esophagectomy through a right thoracoabdominal approach, a multivariate analysis was carried out on preoperative and intraoperative variables in 141 patients with thoracic esophageal cancer. Although postoperative complications occurred in 125 patients, only 7 died of such complications. The multivariate analysis indicated that the retrosternal route was a significant factor predisposing to postoperative atelectasis. Age, preoperative arterial oxygen tension, and volume transfused were significant factors predisposing to postoperative hypoxemia, whereas age, routes other than the intrathoracic route, and volume transfused were significant factors predisposing to prolonged respiratory support. In addition, preoperative total serum bilirubin level and volume transfused were significant factors predisposing to postoperative hyperbilirubinemia; preoperative serum creatinine level was a significant contributing factor for postoperative renal insufficiency; and sex, antesternal route, and substituted colon were significant contributing factors for anastomotic leakage. There were no significant factors predisposing to postoperative pneumonia and liver dysfunction. These significant factors should be taken into consideration not only during perioperative management but also when choosing the operative procedures and extending the surgical indication for esophagectomy through a right thoracoabdominal approach. PMID- 1596129 TI - Retrogastric versus antegastric routing and histology of the right gastroepiploic artery. AB - To maximize use of the right gastroepiploic artery in myocardial revascularization 11 cadavers were studied to determine the shortest route (retrogastric versus antegastric) of the right gastroepiploic artery from its origin to the recipient coronary artery. Any coronary artery could be reached with an in situ right gastroepiploic artery. There was no significant difference between the retrogastric and antegastric routes for any coronary artery, although the former generally is slightly shorter to the vessels on the posterior surface of the heart and the latter to vessels on the anterior surface of the heart. Histological examination of the right gastroepiploic artery in its proximal, mid, and distal segments showed a similar width of intima and media and invariably an almost purely muscular media. Based on the histological similarity of the right gastroepiploic artery to the coronary artery, some scepticism toward liberal use of the right gastroepiploic artery, especially if used as a free graft, is warranted until clinical studies on its long-term patency have been performed. PMID- 1596130 TI - Efficacy of isoproterenol on the failing transplanted heart during early acute rejection. AB - Acute rejection often leads to severe myocardial failure and death. The beneficial hemodynamic effects of isoproterenol in improving immediate postoperative heart failure have prompted its routine use after transplantation. However, because of the physiopathological alterations documented during rejection, an inappropriate response of the graft to isoproterenol administration could be expected. Six dogs received orthotopic transplants and were prepared with implantable devices for serial hemodynamic studies. The studies were performed on the resting unanesthetized subject 3 hours after operation when transient heart failure was present and repeated when myocardial failure secondary to rejection occurred. After basal state measurement, various doses of isoproterenol were infused and the hemodynamic responses during each period were compared. During rejection, the hemodynamic response to 0.05 and 0.10 micrograms.kg-1.min-1 was significantly lower when compared with the response in the postoperative period. To achieve similar postoperative chronotropic and inotropic effects, 0.35 microgram.kg-1.min-1 of isoproterenol was necessary. Isoproterenol is therefore effective in controlling myocardial failure during acute rejection despite a reduced sensitivity of the sinoatrial node and myocardial tissue. PMID- 1596131 TI - Endothelium-mediated relaxation in transplanted aorta. AB - This study compares the vasodilating effect of endothelium-derived relaxing factors (EDRFs) in free arterial grafts with that in their normal control vessels. The infrarenal aorta of Sprague-Dawley rats was transplanted into the same position in other inbred recipient rats. A Krebs buffer solution (4 degrees C) served as the preservation solution. The ischemic time for the grafts (n = 8) was 42 +/- 1 minutes. Two grafts were studied after 3 days and six grafts, after 60 days. Ring segments were cut from all vessels, and isometric contractions were recorded in organ baths. The vessel segments were constricted with noradrenaline, a thromboxane A2 mimic (U-46619), or prostaglandin F2 alpha. Concentration response curves with acetylcholine, which was used as the endothelium-stimulating substance causing release of EDRFs, were obtained. The patency of the grafts was 100%. Acetylcholine induced relaxation in all vessel segments with intact intima, whereas no relaxation was seen when the endothelium was manually removed. No significant differences were found between the grafts and the normal control vessels. Histology of the 60-day grafts showed elastomuscular arteries without intimal thickening and a media consisting of eight to ten muscle layers interrupted by five to six elastic lamellae. Scanning electron microscopy showed no major differences between normal endothelium and the endothelium of 3-day or 60-day grafts. This study indicates that free elastomuscular arterial grafts, in which the morphology of the intima is preserved, will retain their full ability to release EDRFs. PMID- 1596132 TI - Changes in hemodynamics and coronary blood flow during left ventricular assistance with the Hemopump. AB - The Hemopump, a catheter-mounted left ventricular assist device, has been demonstrated to be effective in supporting patients with potentially reversible cardiac failure. The mechanism of recovery of the hearts with this device is not fully understood. The effects of the Hemopump on hemodynamics and coronary blood flow with and without myocardial ischemia and failure have been studied in 8 anesthetized open-chest dogs. Coronary blood flow in the left circumflex artery was assessed with an intracoronary Doppler catheter. Myocardial ischemia was induced by ligation of the left anterior descending and diagonal branches. The effects of maximum support were compared with those of minimum support. The effects of the Hemopump varied according to cardiac function. When cardiac dysfunction was mild, the Hemopump support slightly reduced myocardial O2 demand (assessed by pressure-work index) by volume unloading. When cardiac dysfunction was severe, total bypass was achieved and myocardial O2 demand decreased by 45%, owing to both volume and pressure unloading. Coronary blood flow was incompletely auto-regulated, and the ratio of blood flow to O2 demand increased. PMID- 1596133 TI - Multicenter clinical evaluation of the HeartMate 1000 IP left ventricular assist device. AB - The Thermo Cardiosystems Inc (Woburn, MA) HeartMate 1000 IP left ventricular assist device (LVAD) has been evaluated as a bridge to transplantation in 34 patients for up to 324 days at seven clinical centers in the United States. Sixty five percent of the patients underwent transplantation, 80% of whom were discharged from the hospital. Six additional control patients, transplant candidates who met the entrance criteria but who did not receive the device, were also included in the study. Although 3 (50%) of the control patients received transplants, all 6 died within 77 days of having met the LVAD inclusion criteria (100% mortality). Complications resulting from use of the device were comparable with those previously reported for all ventricular assist devices, except for thromboembolic events: bleeding, 39%; infection, 25%; and right heart failure, 21%. No device-related thromboembolic events occurred, although 1 patient experienced an event related to a mechanical aortic valve in the native heart. None of the complications had a significant negative association with outcome of the patient except for right heart failure. All survivors had a significant improvement in hepatic function before transplantation. Total bilirubin values were reduced by 60% during LVAD support. No significant differences were observed when total bilirubin values were compared at 30 and 60 days after LVAD support and at 30 and 60 days after transplantation in a cohort of 15 patients (p greater than 0.05). The improvement in renal function was less predictable than that of hepatic function. Creatinine values decreased significantly before transplantation; however, the values measured at 30 and 60 days after transplantation were higher than those measured at the same intervals after LVAD support had been initiated, and this increase is presumably related to the immunosuppressive drugs. In conclusion, the HeartMate 1000 IP LVAD has been shown to be effective in supporting end-stage cardiomyopathy patients to transplantation. Thromboembolism, previously regarded as a serious complication with such devices, has not been a problem with this device. Additional patients are being enrolled into the study to further document the safety and effectiveness of this technology. PMID- 1596134 TI - Efficacy of a hydroxyl radical scavenger (VF 233) in preventing reperfusion injury in the isolated rabbit heart. AB - We tested the hypothesis that 3,4,5,-trihydroxybenzamidoxime (VF 233), a demonstrated hydroxyl radical scavenger and an effective Fe3+ chelator, attenuates reperfusion injury and improves isovolumic left ventricular function. Eighteen isolated, perfused rabbit hearts with intracavitary balloons were subjected to normothermic, global ischemia until the initiation of ischemic contracture. Effects on the adenine nucleotide pool metabolites were determined by high-pressure liquid chromatography from right ventricular biopsy specimens before ischemia and at 15-minute intervals throughout reperfusion. In the experimental group (n = 9), a 5-mL bolus of 1 mol/L VF 233 was given immediately before reperfusion and followed by a continuous infusion (0.125 mumol/min). The control group (n = 9) received the vehicle solution at identical times. Rabbits treated with VF 233 had significant improvement in left ventricular function (expressed as percent return of left ventricular peak developed pressure) within 15 minutes of reperfusion (55.0 +/- 3.0 versus 66.2 +/- 4.1; p less than 0.05 by analysis of variance) after global ischemia and remained significantly improved throughout the reperfusion period. Myocardial adenine nucleotide pool intermediates were not significantly different between groups. These results demonstrate that administration of VF 233 significantly improves ventricular function but does not affect adenine nucleotide metabolism after ischemia and reperfusion. PMID- 1596135 TI - Donor heart coronary sinus ostium atresia in a successful cardiac transplant. PMID- 1596136 TI - Arterial correction of double-outlet left ventricule by pulmonary artery translocation. AB - Double-outlet left ventricle is conventionally repaired with an intraventricular tunnel or with an extracardiac conduit when pulmonary stenosis is present. We report a 4-month-old female infant whose surgical correction of double-outlet left ventricle and subpulmonic stenosis was accomplished by pulmonary arterial translocation to the blind right ventricular infundibulum. This approach provided excellent hemodynamic repair without the use of an extracardiac conduit. PMID- 1596138 TI - Aorto-pulmonary artery fistula: an unusual complication of ascending aortic aneurysm. AB - We report an unusual outcome of an ascending aorta aneurysm ruptured into the main pulmonary trunk. After successful emergency repair, an acute respiratory distress syndrome developed perioperatively and complicated the postoperative period. The patient could not be weaned from mechanical ventilation for a long time. The patient was discharged on the 62nd day of admission in good condition. PMID- 1596137 TI - Mediastinoscopic injury to the bronchus: use of in-continuity bronchial flap repair. AB - There is little written in the literature regarding the management of major bronchial disruptions occurring during mediastinoscopy. This report illustrates the use of an in-continuity flap bronchoplasty of middle lobe bronchial tissue to repair such an iatrogenic intermediate bronchus injury. PMID- 1596139 TI - Aortico-right ventricular tunnel. AB - We report successful closure of an aortico-right ventricular tunnel in a 3-month old infant with heart failure. One-year follow-up shows the child to be developing normally. PMID- 1596140 TI - Development of malignant hyperthermia during mitral valve replacement. AB - Malignant hyperthermia is a genetically predisposed, potentially fatal disorder triggered by anesthetic agents. The early diagnosis and treatment of malignant hyperthermia is essential, yet often difficult, because the signs and symptoms of this disorder are not unique to the disease. When the patient is also undergoing cardiopulmonary bypass this disorder may be very difficult to recognize. In this article, we report a case of malignant hyperthermia diagnosed during mitral valve replacement and discuss the preoperative and postoperative management possibilities. The unusualness of this case stems from the fact that the patient had centronuclear myopathy. Although reported with other types of myopathies, centronuclear myopathy has rarely been associated with malignant hyperthermia. This episode of malignant hyperthermia was diagnosed by intraoperative measurements showing increased oxygen consumption despite hypothermic cardiopulmonary bypass. PMID- 1596141 TI - Coronary bypass with both internal mammary and inferior epigastric arteries. AB - A patient having undergone triple coronary artery bypass grafting with the left internal mammary artery and both shorter saphenous veins was reoperated on because of occlusion of the venous grafts. As there was no other vascular substitute available, the right internal mammary artery and both inferior epigastric arteries were used to achieve myocardial revascularization. This case demonstrates that bilateral internal mammary arteries and inferior epigastric arteries can be used safely. PMID- 1596142 TI - Right latissimus dorsi cardiomyoplasty for left ventricular failure. AB - Recent experimental studies have shown that cardiomyoplasty using the right latissimus dorsi provides excellent hemodynamic augmentation. Based on these experimental findings, this procedure was performed in a 40-year-old man with a dilated cardiomyopathy after a large myocardial infarction. The patient tolerated the procedure well and has had marked functional improvement. Examination 6 months after operation demonstrated decreases in right atrial pressure, pulmonary capillary wedge pressure, and left ventricular end-diastolic volume. In addition, increases were noted in cardiac output, stroke volume, left ventricular stroke work, right ventricular ejection fraction, and left ventricular ejection fraction. Because of this promising clinical result, we have started a series of right latissimus dorsi cardiomyoplasties for left ventricular failure. PMID- 1596143 TI - Percutaneous localization of pulmonary nodules for thoracoscopic lung resection. AB - A limiting factor in removing pulmonary nodules by videothoracoscopic techniques is the inability to locate lesions deep within the substance of the lung. We describe a technique in which a hook wire commonly used to localize nonpalpable breast lesions is placed percutaneously into the lung nodule preoperatively. Using the wire anchored into the lung as a guide, the target lesion can be successfully identified and removed thoracoscopically. PMID- 1596144 TI - Technique for replacing the ascending aorta and aortic valve with a modified Bentall's operation. AB - Composite graft replacement of the aortic root and valve poses the challenge of reimplanting both coronary ostia. The technique of sandwiching the freed button of aortic wall bearing the coronary artery ostium between an outer Teflon felt washerlike buttress and the inner composite graft provides a leak-proof anastomosis while reestablishing direct graft to coronary artery continuity regardless of the location of the coronary ostia or type of root pathology. PMID- 1596145 TI - Surgical treatment of tricuspid regurgitation. AB - The technique of tricuspid valve repair for tricuspid regurgitation has been used effectively since 1961. The first publication of the method appeared in 1965 in the Annals of Surgery. The procedure has changed little since that time and has afforded excellent long-term results. The procedure consists of excluding the annulus of the posterior leaflet of the tricuspid valve. The technique is simple, fast, hemodynamically effective, and durable. It carries no risk of heart block because the posterior leaflet annulus is far from the conduction system. An inferior caval snare may produce inadequate drainage with resulting increased back pressure on the liver leading to hepatocellular necrosis and lethal postoperative liver dysfunction in 3 to 5 days. Therefore, an inferior caval snare is never used when repairing or replacing the tricuspid valve for acquired or rheumatic heart disease. Morbidity and mortality are also decreased by restricting fluids in the postoperative period. PMID- 1596146 TI - Asymptomatic bronchogenic cysts: what is the best management? AB - The management of patients with uncomplicated bronchogenic cysts has evolved over the last decade with the development of more precise diagnostic techniques and a better understanding of the variable natural history of these lesions. Although an aggressive surgical approach is still indicated for infants and children, it is acceptable to treat asymptomatic bronchogenic cysts in adults in a conservative manner. Observation alone may be indicated for small, classic, asymptomatic cysts. The use of mediastinoscopy or percutaneous or transbronchial needle techniques for carinal or paratracheal cysts offers the option of fluid aspiration or wall biopsy, thus avoiding thoracotomy. An air-fluid level in the cyst, the presence of malignant cells in the aspirate or biopsy, the development of symptoms, or enlargement or recurrence of the cyst on follow-up examination mandates complete surgical removal at thoracotomy. This is also indicated for intraparenchymal bronchogenic cysts, which are more prone to bronchial communication and infectious complications and for which the distinction from a carcinoma with a cystic component may be difficult. PMID- 1596147 TI - Practice guidelines in cardiothoracic surgery. PMID- 1596148 TI - Cystic and bullous lung disease. PMID- 1596149 TI - Histology of the internal mammary artery versus the inferior epigastric artery. PMID- 1596150 TI - Patent foramen ovale: a cause of hypoxemia in patients on left ventricular support. PMID- 1596151 TI - Radial nerve injury in patients undergoing coronary artery bypass grafting. PMID- 1596152 TI - Nonabsorbable interrupted sutures for tracheal anastomosis in childhood. PMID- 1596153 TI - Open coronary endarterectomy, saphenous vein patch reconstruction, and internal mammary artery grafting. PMID- 1596154 TI - Semb ligature carrier. PMID- 1596155 TI - Thoracic surgeons and clinical trials: a manifesto for the future. PMID- 1596156 TI - Effects of temperature and flow rate on regional blood flow and metabolism during cardiopulmonary bypass. AB - Eleven dogs were subjected to a 150-minute period of cardiopulmonary bypass that consisted of a high-flow, normothermic phase, a high-flow, hypothermic phase, a low-flow, hypothermic phase, and then a high-flow, rewarming phase. Regional blood flow and oxygen consumption to the brain, intestines, kidney, and hind limb were determined at baseline and at 10-minute intervals during cardiopulmonary bypass. Blood flow to the carotid artery, superior mesenteric artery, and renal artery declined significantly with hypothermic cardiopulmonary bypass whereas blood flow to the femoral artery increased significantly. Although total body oxygen consumption returned to baseline values at the end of the rewarming phase, oxygen consumption for these regions differed somewhat from their baseline values. We conclude that blood flow during hypothermic cardiopulmonary bypass is shunted to skeletal muscle, particularly with high pump flows. Additionally, the return of total body oxygen consumption to baseline after rewarming is not necessarily reflected at the regional level. PMID- 1596157 TI - Coronary sinus cardioplegia: clinical trial with only retrograde approach. AB - The cases of 100 consecutive patients who underwent coronary artery bypass grafting with coronary sinus (retrograde) cardioplegia (group R) without the antegrade-retrograde approach were reviewed. To evaluate the safety and the efficacy of this technique, another 100 consecutive patients who underwent a similar procedure but with conventional aortic root (antegrade) cardioplegia (group A) were used as a comparison. The two groups were similar with respect to age, male to female ratio, associated medical problems, extent of coronary artery disease, mean preoperative ejection fraction (0.56 +/- 0.13 versus 0.53 +/- 0.18), pump time (113.1 +/- 43 versus 111.7 +/- 38 minutes), aortic cross-clamp time (57.4 +/- 20 versus 60.8 +/- 23 minutes), number of grafts per patient, level of hypothermia, complication rate, rate of postoperative myocardial infarction (4% versus 3%), and mortality rate (2% versus 2%). Hemodynamic measurements were made 6 hours after operation in 59 patients in group R and 47 patients in group A. The cardiac index, left ventricular stroke work index, and right ventricular stroke work index were better in group R but not significantly so (p greater than 0.05). However, only 27% of patients in group R required a temporary pacemaker, and only 9% needed inotropic agents after 6 hours of operation in contrast to 51% and 42%, respectively, in group A (p less than 0.05). There were no complications from catheter intubation. In group R, right ventricular wall temperature (11 degrees +/- 3.6 degrees C) was higher than the septal (10.8 degrees +/- 3.2 degrees C) and left ventricular wall temperatures (9.1 degrees +/- 2.8 degrees C) (p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596158 TI - Esophageal carcinoma: esophageal ultrasound assessment of preoperative chemotherapy. AB - The effect of preoperative chemotherapy in the treatment of esophageal carcinoma is difficult to assess because of the inadequacies of clinical staging. Endoscopic esophageal ultrasound (EUS) has been shown to be accurate in the clinical determination of depth of tumor invasion (T) and regional lymph node status (N). Therefore, EUS may be useful in assessing the effect of preoperative chemotherapy in the treatment of esophageal carcinoma. Eleven patients with operable adenocarcinoma of the esophagus or esophagogastric junction underwent staging by EUS before treatment. This was followed by two courses (10 patients) or one course (1 patient) of chemotherapy: etoposide, 120 mg/m2 for 3 days; doxorubicin hydrochloride, 20 mg/m2; and cisplatin, 100 mg/m2. Restaging by EUS was done after treatment. Ten patients then underwent resection of the tumor with lymphadenectomy. One patient was found to have metastatic disease at thoracotomy and did not undergo resection. However, tissue sampling was adequate for the determination of pathological stage. Independent pathological determinations of T and N were then obtained. On completion of chemotherapy, 9 patients (82%) had relief or reduction of preoperative symptoms, and 9 patients (82%) had either no evidence of tumor or reduction of tumor size by endoscopy. Despite this clinical and endoscopic response, no patient had EUS-documented and pathology-confirmed reduction of T. However, 2 patients had EUS-documented and pathology-confirmed progression of N. The accuracy of EUS in the determination of T was 82% and of N, 73%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596159 TI - Implantation of cardioverter defibrillators in the post-sternotomy patient. AB - In an attempt to minimize the hazards of redo sternotomy or thoracotomy in patients who have undergone previous cardiac procedures, a technique has been developed for cardioverter defibrillator implantation that involves dissection through a left subcostal incision and placement of extrapericardial defibrillation patches. This approach was used in 22 consecutive patients who required an implantable cardioverter defibrillator 4 to 156 months after previous median sternotomy. Defibrillation threshold energy was less than or equal to 20 J in every patient. Ninety-one percent of patients were extubated during the first 24 hours and were transferred out of the intensive care unit by the second postoperative day. One patient died of an acute myocardial infarction 3 days postoperatively (1/22, 4.5%). It was necessary to replace one lead for mechanical failure of an adapter, one patch required repositioning, and 1 patient needed drainage of a persistent pleural effusion (3/22, 13.6%). No further complications occurred during 3 to 27 months of follow-up. Advantages of the subcostal approach included prompt extubation, a single incision, and minimal morbidity. This approach is safe and effective, and is the method of choice for implantation of a cardioverter defibrillator in patients who have undergone prior sternotomy. PMID- 1596160 TI - Time to first pulse after automatic implantable cardioverter defibrillator implantation. AB - Should automatic implantable cardioverter defibrillator (AICD) power sources be explanted and discontinued if they have not pulsed during the first generator life? We have followed 59 patients an average of 23 months (range, 3 days to 8.4 years) after AICD implantation. The indication for AICD implantation was based on clinical dysrhythmia, history of sudden death, and findings at electrophysiologic study. Thirty-eight of 59 patients (64%) had experienced sudden death and 52/58 (90%) were inducible at electrophysiologic study. Excluding 5 inappropriate pulsing episodes, 31 of 59 patients (53%) had 235 pulses (range, 1 to 36; median, 2 pulses). The time to first pulse after implantation ranged from 1 day to 3.5 years with a median time of 2 months. In 6 patients, the first pulsing occurred later than 1 year after AICD implantation. Fifteen generators demonstrating impending power source failure have been replaced in 11 patients. Power source depletion occurred at an average of 24.1 months (range, 8 to 40 months). In 3 patients, the first pulsing occurred after generator depletion and replacement. By univariate analysis, none of 13 variables (sex, age, cardiac disease process, functional class, previous myocardial infarction, sudden death history, ejection fraction, type of dysrhythmia, inducibility with electrophysiologic testing, number of extra stimuli required for induction, left ventricular aneurysm resection, endocardial resection, or concomitant operation) was found to be a predictor of pulsing (p greater than 0.05). We conclude that the majority of patients with pulses after AICD implantation will have them during the first 6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596161 TI - Pulmonary embolism in the cardiac surgical patient. AB - Pulmonary embolism (PE) is thought to occur infrequently after cardiac operations, possibly because systemic heparinization during cardiopulmonary bypass prevents deep vein thrombosis. This retrospective study was undertaken to determine the actual incidence of PE after cardiac operations and to identify risk factors. Between January 1, 1985, and December 31, 1989, 5,694 adult patients (greater than 18 years old) had open heart operations at the Johns Hopkins Hospital. Thirty-two patients (20 men and 12 women) had PE within 60 days of operation, an overall PE incidence of 0.56%. The diagnosis of PE was established by ventilation/perfusion scan, pulmonary angiogram, or autopsy. Mortality among patients with PE was 34%. Using a case-control method, preoperative and postoperative risk factors for PE were identified by multivariate and multiple logistic regression analyses. Preoperative risk factors included bed rest (p less than 0.003), prolonged hospitalization before operation (p less than 0.004), and cardiac catheterization performed through the groin within 15 days before operation (p less than 0.01). Post-operative risk factors were congestive heart failure (p less than 0.008), prolonged bed rest (p less than 0.05), and deep vein thrombosis (p less than 0.03). This study demonstrates that PE is an unusual complication after cardiac operations, has a high mortality rate, and is often related to perioperative immobility and recent groin catheterization. These results also suggest that minimizing preoperative hospital stay may be important in PE prophylaxis. PMID- 1596162 TI - Analysis of determinants of ventricular fibrillation induced by reperfusion: dissociation between electrical instability and myocardial damage. AB - To assess the underlying mechanisms of ventricular fibrillation induced by myocardial reperfusion after cardioplegic arrest, 62 patients undergoing an open heart operation were divided into two groups based on the absence (group 1, n = 37) or the development (group 2, n = 25) of reperfusion-induced ventricular fibrillation. There was no close relationship between the incidence of reperfusion-induced ventricular fibrillation and aortic clamp time. On reperfusion, the time to onset of cardiac activity was similar in groups 1 (2.4 +/- 1.8 minutes) and 2 (1.9 +/- 1.1 minutes). At that time, there was no significant difference in values of arterial oxygen and bicarbonate contents, pH, or base excess between the two groups, but myocardial temperature was significantly higher in group 2 (25.6 degrees +/- 3.4 degrees versus 27.6 degrees +/- 2.4 degrees C; p less than 0.05). In addition, serum levels of sodium (123.9 +/- 4.2 versus 126.1 +/- 3.7 mmol/L; p less than 0.05) and calcium (0.80 +/- 0.07 versus 0.84 +/- 0.05 mmol/L; p less than 0.05) were significantly higher and serum potassium levels (3.98 +/- 0.58 versus 3.55 +/- 0.61 mmol/L; p less than 0.02) and the serum potassium to calcium ratio (4.94 +/- 0.90 versus 4.29 +/- 0.72; p less than 0.01) significantly lower in group 2. Postoperative serum levels of the myocardial-specific isoenzyme of creatine kinase and myoglobin were similar in both groups. By multivariate analysis, shorter ischemic time, higher myocardial temperature, higher serum sodium concentration, and lower serum potassium to calcium ratio were found to influence induction of reperfusion induced ventricular fibrillation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596163 TI - Trauma. The motor end plate of violence. PMID- 1596164 TI - Future shock. PMID- 1596165 TI - Surgical critical care. The next challenge in regionalized trauma systems. PMID- 1596166 TI - Recidivism in an urban trauma center. AB - The incidence of recurrent injury requiring evaluation and treatment at an urban trauma center was assessed by examination of data from the registry of an urban trauma unit. A subgroup of 342 recidivists sustained 711 traumatic injuries. This represented 6.4% of trauma service activations or consultations. The rates of recurrence in random groups of 100 patients with trauma and 50 patients with traumatic deaths were 5% and 12%, respectively. These rates of recurrent injury are lower than those of several previous reports. Comparison of patients with recurrent episodes of trauma with patients who experience a single episode of trauma revealed significant differences in age, sex distribution, mechanism of injury, and fatal outcomes. Recidivists averaged only 7.9 months between episodes of injury. In patients with recurrent trauma with fatal outcomes, the mean interval between initial injury and death was 18.8 months. Early identification of patients at high risk for recurrence may provide an opportunity for behavior modification. PMID- 1596167 TI - Injury and violence in Los Angeles. Impact on access to health care and surgical education. AB - The Los Angeles County (California) Trauma Hospital System was designed to ensure that all patients requiring specialized trauma care would be transported directly to a trauma center using established trauma triage criteria. The designation and implementation of all level 1, 2, and 3 (rural) trauma centers were completed between October 1983 and July 1985. However, by February 1, 1985, one level 2 trauma center withdrew, and nine other level 2 and 3 trauma centers followed suit over the next few months and years. The reasons for closure of these 10 trauma centers were almost exclusively related to economic factors. The major impact of trauma center closure on surgical educational programs at the Drew University of Medicine and Science and the Martin Luther King, Jr/Charles R. Drew Medical Center have been additive and cumulative. The high volume of patients with trauma has been cited, sometimes correctly and sometimes incorrectly, as the primary reason for a lack of access to health care for patients without trauma. We have developed a blueprint for survival that, when fully implemented, will improve access to health care for all residents in our catchment area and optimize surgical education. While the Los Angeles County Trauma Hospital System has had many difficulties during the last 9 years, the population it serves is greater than that in 42 states in the United States. The experiences gained in Los Angeles County may be beneficial to statewide systems in the United States and in countries of comparable size. PMID- 1596169 TI - Visceral injuries. AB - Abdominal visceral injuries are encountered by every surgeon who deals with trauma. It is simple and useful to divide abdominal visceral injuries into those caused by penetrating mechanisms of injury and those due to blunt mechanisms. Determination of the need for operative intervention is generally easier after penetrating trauma. Gunshot wounds to the abdomen should be explored, as should stab wounds to the anterior abdomen that penetrate the fascia. A midline incision is the standard approach to abdominal visceral injuries because of its ease and versatility. Abdominal exploration should be consistent and systemic so as not to miss significant injuries. Hollow viscus injury is most common after penetrating injury, while blunt injury most often results in injury to solid viscera. Diagnostic and operative aspects of the treatment of specific visceral injuries are reviewed. PMID- 1596168 TI - Blood in our streets. The status and evolution of trauma care systems. AB - Injury is our nation's leading public health problem. Victims of violence need expert and immediate medical attention. A model exists for optimal care of the injured patient--the trauma care, the components of the ideal, inclusive history of trauma care, the components of the ideal, inclusive trauma care system, its efficacy, and the challenges and opportunities facing those who advocate such systems. PMID- 1596170 TI - Epidemiologic changes in gunshot wounds in Washington, DC, 1983-1990. AB - The purpose of this study was to examine temporal patterns in gunshot wound admission rates and wound profiles from 1983 through 1990 at a level I trauma center in Washington, DC. Data on trauma admissions were collected at the time of admission. Records were reviewed to identify patients admitted for gunshot wounds from assaults. Data on the number and location of entrance gunshot wounds, survival, complications, length of stay in the intensive care unit, and total inpatient days were recorded. Admissions due to gunshot wounds grew at an exponential rate beginning in 1987 and reached a level from 1989 through 1990 three times higher than the preepidemic rate. The mean number of entrance gunshot wounds per patient grew from 1.44 before the epidemic to 2.04 from 1988 through 1990. Multiple thoracic wounds became relatively more common from 1988 through 1990. This increase was partially responsible for reversing a downward trend in patient mortality. Temporal changes in admission rates and wound profiles were consistent with the city's epidemic of drug-related violence and with a shift in weaponry toward high-capacity, semiautomatic handguns. PMID- 1596171 TI - Trauma in the geriatric patient. AB - Elderly individuals are living longer, healthier, and more active lives, and, in the process, they are continually exposed to the risk of injury. Trauma is now the fifth most common cause of death in people over the age of 65 years, and the elderly suffer disproportionately high injury-related mortality rates compared with younger adults. They consume a vast portion of health care resources and their care precipitates some of the most difficult ethical and sociologic questions in modern medicine. Physiologically, the elderly present a unique and complex picture that requires an understanding of the process of aging and the concomitant effects of acquired diseases. As surgeons involved in the care of the injured, we find ourselves becoming more frequently involved with this national dilemma. This review provides some insights and guidelines for the care of the injured elderly, with the hope of improving our understanding and their outcome. PMID- 1596172 TI - Pancreatic ascites and effusion. Risk factors for failure of conservative therapy and the role of octreotide. AB - The possible risk factors for failure of medical therapy were examined in 23 patients with pancreatic ascites or effusion. The ascites or effusion resolved completely in 10 patients after a mean (+/- SEM) of 30 +/- 2 days of conventional medical treatment. In five patients in whom conventional medical therapy failed, the addition of an octreotide (SMS 201-995) analogue to the medical therapy led to a resolution of the ascites (three patients) or effusion (two patients). Six patients underwent surgery after failed medical therapy, one patient died while receiving conservative therapy, and one patient refused hospital treatment. Serum sodium and albumin levels were significantly lower, and the ratio of total fluid protein to total serum protein was significantly higher in the group that failed to heal in response to conventional medical therapy. Nine of 11 patients with mild to moderately severe chronic pancreatitis healed in response to conservative therapy. Only one of 10 patients with advanced pancreatitis healed in response to conventional medical therapy. Our results suggest that a selective surgical approach is warranted to treat pancreatic ascites and effusion. In patients with mild or moderately severe pancreatitis, medical therapy is recommended. Patients with advanced pancreatic disease should be selected for early surgery. Octreotide may be useful in the patient in whom surgery may be associated with a prohibitive morbidity or mortality. PMID- 1596174 TI - Analysis of surgical participation in the Advanced Trauma Life Support course. What are the goals and are we meeting them? AB - Advanced Trauma Life Support (ATLS) course records spanning 4 years were examined and American College of Surgeons members in Washington State surveyed to gain further information on ATLS course participants, skills utilization, and hospital credentialing. Thirty-seven (9.7%) of 382 course participants were trained general surgeons, 56 (14.7%) were surgical residents, and 12 (3.1%) were surgical specialists. One hundred thirty-six (35.6%) of the participants were primary care physicians and 115 (30.1%) were emergency physicians. Surgical residents, primary care physicians, and emergency physicians tended to be overrepresented in ATLS courses in comparison with their general distribution. Fully trained surgeons and surgical specialists were underrepresented. Course participants represented 3.8% of all physicians involved in patient care in the state. Only 6.4% of all active general surgeons in the state were participants, while 39% of active emergency physicians participated. The successful completion rate was 94% (98% for surgeons and 92% for nonsurgical physicians). Thirty-one percent of all American College of Surgeons survey respondents (31% of urban practitioners and 21% of rural practitioners) reported current ATLS qualification. Advanced Trauma Life Support qualification was reported by 31% of respondents as a requirement for taking trauma/emergency department call. Surgeons with a preference not to treat patients with trauma were less likely to have ATLS qualification. More than half of those who reported ATLS qualification had not performed a tracheal intubation, cricothyroidotomy, pericardiocentesis, or emergency department thoracotomy in the previous year. Participation of surgeons in ATLS courses is low, particularly among rural practitioners. Impetus for participation appears related to requirements for hospital staff credentialing and preferences for treating patients with trauma. Performance of procedures taught in the course is rare. Strategies to increase participation need to be formulated and implemented. PMID- 1596173 TI - Regulation of tumor necrosis factor production in healthy humans and in patients with cancer. AB - To study the factors that influence cytokine release, the effect of endotoxin on in vitro tumor necrosis factor production by monocytes from debilitated patients with cancer (n = 6) was compared with that from healthy controls (n = 5). Spontaneous and endotoxin-stimulated monocyte tumor necrosis factor production was similar in patients with cancer and controls. However, with total peripheral blood mononuclear cells, enhancement of tumor necrosis factor production by endotoxin in patients with cancer (46 +/- 12, mean +/- SEM) was greater than in controls (0% +/- 7%). This enhanced response correlated with reduced peripheral blood mononuclear cell blastogenesis in response to phytohemagglutinin (r = .66) and could be partially reversed in vitro by addition of exogenous interleukin 2. Thus, a component of total peripheral blood mononuclear cells (probably T cells) seems to influence monocyte cytokine production in response to endotoxin. Moreover, this regulatory component is decreased in patients with cancer, correlates with decreased peripheral blood mononuclear cell blastogenesis, and can stimulated with interleukin 2. PMID- 1596175 TI - Do graduated compression stockings and pneumatic boots have an additive effect on the peak velocity of venous blood flow? AB - Graduated compression stockings and intermittent pneumatic compression boots reduce the incidence of deep vein thrombosis. Recent studies suggest that the simultaneous use of these devices may have a synergistic prophylactic effect; however, conflicting reports also exist. Using duplex imaging, we analyzed the effect on peak venous velocity in the superficial femoral vein produced by the individual and simultaneous use of graduated compression stockings and intermittent pneumatic compression boots. Normal volunteers and postoperative patients were examined. The use of intermittent pneumatic compression boots significantly increased the peak venous velocity relative to rest, whereas the use of graduated compression stockings did not alter the peak venous velocity. Also, the addition of graduated compression stockings to legs already being treated with intermittent pneumatic compression boots did not produce a further augmentation of peak venous velocity. This study demonstrates that the simultaneous use of graduated compression stockings and intermittent pneumatic compression boots does not produce a synergistic augmentation of peak venous velocity in the superficial femoral vein. PMID- 1596176 TI - Measuring and managing quality of surgery. Statistical vs incidental approaches. AB - New rules for quality assurance provoked a comparison of effects of two approaches used concurrently for 14 years. In an incidental approach, a multidisciplinary conference reviewed all postoperative complications as they occurred and attributed each to one of six causes. Remedies were instituted and data were filed. In a statistical approach, death and complication rates were computed annually and compared with previous years' rates and with rates reported to Congress as national norms. Statistics suggested acceptable quality in each specialty but calculations were tedious and differences achieved significance too rarely or too slowly to identify problems, protect patients, and improve care. The incidental approach was popular and produced immediate improvements in patient care. Conferees attributed one half of complications to errors. Frequent acknowledgment of susceptibility to error may contribute to the safety and quality shown by our statistics. PMID- 1596177 TI - Implantation of antibiotic-releasing carriers and in situ reconstruction for treatment of mycotic aneurysm. AB - Four patients with mycotic aneurysm of the extracranial carotid artery, the innominate artery, the ascending aorta, and the infrarenal aorta were treated with local implantation of antibiotic-releasing carriers after resection of the aneurysm, excision of all infected tissue, and in situ reconstruction by prosthetic graft replacement in two patients and patch plasty in two patients. The patient with a mycotic aneurysm of the ascending aorta was operated on again 1 month after the first operation because of a second mycotic aneurysm located on the aortic arch. No early or late signs of recurrent infection were seen on clinical and laboratory postoperative follow-up done between 9 and 16 months or on duplex scan or computed tomography done at these times. Implantation of antibiotic-releasing carriers after debridement of all infected tissue and in situ reconstruction for treatment of mycotic aneurysm was performed successfully in four patients with this life-threatening condition. PMID- 1596178 TI - Neutrophilia, oxygen free radicals, and abdominal adhesions. PMID- 1596180 TI - [Clinical pathology due to hepatitis B virus]. AB - All information accumulated during last 10 years allows the view on the alterations produced by hepatitis B virus as ubiquitous. Extrahepatic pathology in hepatitis B is associated with the immunocomplex and immunocellular mechanisms but more frequently with their combination. Wide spread of hepatitis B virus infection and high level of morbidity, persistence of the virus in the organism necessitate further study of clinical pathology associated with this virus. PMID- 1596179 TI - [Aspects of modeling, etiology and pathogenesis of experimental sepsis]. AB - An experimental model of sepsis is developed that allows one to reproduce septicopyemia and septicemia taking into account the biological properties of bacteria which determine sepsis dynamics, its form and localization of metastatic pyemic foci. The dependence of the sepsis manifestation upon the functional state of polynuclear leucocytes is revealed. The irreversibility of the process after the bacterial colonisation of the inner organs is shown a general increase of the histohematic barrier permeability facilitates the release of flora, mainly intestinal one, into the circulation and organs. PMID- 1596181 TI - [New developments in the pathogenesis and treatment of peritonitis]. AB - The authors put forward the idea that a leading factor in the pathogenesis of acute generalized peritonitis (AGP) is not inflammation but intoxication approaching in its intensity that of bacterial-toxic shock. The intoxication appears immediately after the catastrophe in the abdominal cavity, results in the microcirculation disturbances in all inner organs, degenerative changes in the small bowel nerves, etc. Damages in the organs due to intoxication develop several hours earlier than peritoneal inflammation which is influenced by the intoxication. The patients die during the toxic stage after the operation not from the peritoneal inflammation which is lacking but from the irreversible homeostatic disturbances with the signs of bacterial-toxic shock. Some tests for postoperative prognosis and treatment scheme are suggested based on the new concepts of AGP. They proved to be useful in the clinics. PMID- 1596182 TI - [Histoautoradiographic characteristics of candidiasis pneumonia in combination drug therapy]. AB - The lungs and organs of guinea pigs infected with fungus Candida against the background of cyclophosphamide immunodeficiency and therapy with antibiotics were studied morphologically. Secondary immunodeficiency and dysbacteriosis are shown to influence considerably the ability of fungal cells to utilize DNA and RNA precursors (tritium-labelled thymidine and uridine). Historadioautography allowed one to evaluate functional state of the infectious agent and host cell responses. PMID- 1596183 TI - [Fungus imitators in the newborn brain]. AB - Morphology of the basophilic fibers erroneously considered by some authors as the fungus mycelium found in 4 newborns with periventricular leukomalacia is studied at the light- and electron microscopic level. Differential diagnosis between fungi and these structures which, in the authors opinion, are the damaged non myelinated axons, including those with mineralization, is presented. PMID- 1596184 TI - [Immunohistochemical characteristics of serum nephrotoxic nephritis in rats: effect of methylprednisolone and potassium fenozan]. AB - Late heterologous and autologous stages of nephrotoxic serum nephritis were studied against the background of MP-induced immunological suppression and PP effect on arachidonic acid metabolism. MP prevented mononuclear infiltration of the renal glomerulus and the development of severe morphological lesions in the autologous stage, while cell culture and mononuclear leukocyte number drastically decreased. PP did not significantly influence the autologous stage of the nephritis though resulted in marked proliferation in both renal glomerulus and mesangial cell culture during the heterologous stage. In spite of more pronounced proliferative activity of mesangial cells interleukin-I level was lower than in animals with nephritis untreated with PP. The enhancement of the proliferative reaction is obviously related, apart from interleukin-I, to the effect of other growth factors. PMID- 1596185 TI - [Morphologic features of chronic otitis media in children]. AB - Surgical material from the middle ear of 80 children at the age of 5 months to 15 years who suffered from chronic otitis media as well as 20 temporal bones of foetuses (24-36 weeks) and stillborns without ear diseases are studied. It is established that the character of topography and inflammation in the ear is associated with persistence of myxoid tissue and a low degree of differentiation in the retrotympanic regions of the middle ear this excluding the possibility of its functioning as a local immune barrier. Myxoid tissue is the main reactive substrate of purulent otoantritis and otomastoiditis in children of early age and, as mesenchymal tissue with angioplastic potencies, may be regarded as a conductor of a secondary cholesteatoma of the attico-antral region. PMID- 1596186 TI - [Brain cryptococcosis in HIV infection]. AB - A 30-year-old female with HIV-infection (AIDS-stage) died with generalized, including meningoencephalitis, infection. Fungi found in the brain were identified as Cryptococcus neoformans. Fungal cells were also found in the lungs and in the necrotic phlegmon of soft tissue i. e. there was a generalized Cryptococcus infection. PMID- 1596187 TI - [Morphologic manifestations of cutaneous and visceral cryptococcosis]. AB - It is a review of the literature plus the description of the three cases of the skin and visceral cryptococcosis diagnosed after the histologic examination of surgical and biopsy material. As clinical diagnosis is difficult, the microscopy of glasses-"prints" from damaged organs stained with a black dye for a rapid revealing of cryptococci is recommended. An important role of hormonal preparations and antibiotics withdrawal is pointed out as their use activates the fungal flora. PMID- 1596188 TI - [Generalized actinomycosis in an 8-month-old child]. AB - Generalized actinomycosis as well as other fungal lesions are typical for children with congenital or acquired immunodeficiencies. The present case of generalized actinomycosis developed against the background of the immunodeficiency resulting from dysplasia of the thymus and lymphoid tissue after chemotherapy of abdominal tumour. PMID- 1596189 TI - [A method for studying the three-dimensional structure of organs and tissue in pathology]. AB - A new technique of scanning electron microscopy for visualization of hidden cellular surfaces in organs and tissue has been developed. It employs the sample incubation in 30% potassium hydroxide and 96% alcohol mixed in equal amounts and dissociation until single cells appear in the solution, this being checked under phase-contrast microscope. The method is beneficial in non-standard cases of three-dimensional organization of organs and tissues. PMID- 1596190 TI - [A modified method of endothelium impregnation suitable for pathology studies]. AB - Prolonged fixation worsens the quality of the endothelium boundaries silver impregnation. A modified method is suggested: the vessel segment is fixed in 2.5% glutaraldehyde for 5 min with subsequent conservation in the saline till the impregnation. Incubation in the saline for 24 hours preserves the susceptibility of endothelium to silver impregnation. PMID- 1596191 TI - [Nikolai Fedotovich Mel'nikov-Razvedenkov (the 125th anniversary of his birth]. PMID- 1596192 TI - [Pathology and pathogenesis of sepsis]. AB - The key problems of the theory of sepsis and criteria of its postmortem diagnosis are discussed on the basis of pathological and bacteriological study of about 4000 purulent-septic diseases observed for the last 40 years in the pathology department of N. V. Sklifosovsky Moscow Research Institute of Emergency Medical Aid (sepsis after abortion, surgical and iatrogenic sepsis, acute septic endocarditis, purulent peritonitis, mediastinitis, pleuritis, phlegmons of body and limbs, bacterial shock, etc.). Sepsis, according to the author, is a generalized infectious disease developing acyclically, produced mainly by purulent coccal flora and having the course of septicopyemia. A metastatic purulent focus is an obligatory sign of the generalization. Septicemia is a local inflammatory process produced mainly by bacterial gram-negative flora. It can be a prologue of sepsis but more frequently develops in two directions: 1) purulent resorptive fever with an acute, subacute and chronic course; 2) bacterial shock with a fulminant course and high lethality. PMID- 1596193 TI - Violent brain injuries by gunshot in Duval County, Florida, 1989-1991. PMID- 1596195 TI - The role of a sleep disorder center in evaluating sleep violence. AB - To review the state-dependent nature of violence and present a clinically useful classification of sleep violence, this article reviews our experience with sleep related violence, establishing a differential diagnosis, methods of evaluation, and treatment options. The study occurs in a full-service clinical sleep disorders center evaluating approximately 1000 patients annually with an active participation of 16 physicians representing seven specialties. The patients were self-, physician-, or court/social service-referred for evaluation of violent or injurious behaviors associated with the sleep period. Interventions were dependent on the final diagnosis following clinical and (usually) sleep laboratory evaluation. The main outcome measures were self-reported. During routine clinical evaluations at a multidisciplinary sleep disorder center, it has become apparent that violence is often state-dependent, occurring only during the sleep period, resulting from a number of both neurologic and psychiatric conditions (including malingering and Munchausen syndrome by proxy). In such cases, careful clinical and laboratory evaluation usually results in a specific diagnosis, with effective therapeutic recommendations. Violence may be state dependent. It is clear that violent behaviors may arise from the sleep period, often without conscious awareness on the part of the subject. This has social, forensic, and clinical implications, and may help contribute to the understanding of violence in general. PMID- 1596194 TI - Violence. The neurologic contribution: an overview. AB - The role of cultural forces in either promoting or discouraging interpersonal violence is so obvious that it has been allowed to obscure the part played by biologic disorders in determining responses to endogenous and environmental challenges. Neuroscientists and clinicians have demonstrated, however, that aggression has a neuroanatomic and chemical basis, that developmental and acquired brain disorders contribute to recurrent interpersonal violence, that both biologic and sociologic factors are involved, and that to ignore either is to invite error. PMID- 1596196 TI - Murder, insanity, and medical expert witnesses. AB - Recent advances in the ability to study brain anatomy and function and attempts to link these findings with human behavior have captured the attention of the legal system. This had led to the increasing use of the "neurological defense" to support a plea of not guilty by reason of insanity. This article explores the history of the insanity defense and explores the role of the medical expert witnesses in integrating clinical and laboratory findings, eg, computed tomographic scans, magnetic resonance scans, and single-photon emission computed tomographic scans. Three cases involving murder and brain dysfunction are discussed: the first case involves a subarachnoid hemorrhage resulting in visual perceptual and memory impairment; the second case, a diagnosis of Alzheimer's disease; and the third case, the controverted diagnosis of complex partial seizures in a serial killer. PMID- 1596197 TI - Cerebral metabolism and depression in patients with complex partial seizures. AB - Twenty-three patients with complex partial seizures were evaluated with 18F-2 deoxyglucose positron emission tomography and with the Beck Depression Inventory. Five of 10 patients with left and zero of eight with right temporal electroencephalographic foci had depressive symptoms; one of five patients with poorly localized electroencephalographic foci also scored in the depressed range. Temporal, frontal, caudate, and thalamic normalized glucose metabolic rates among five patients with depressive symptoms and well-localized left temporal epileptogenic regions were compared with five patients without depressive symptoms but with similar electroencephalographic characteristics. Multifactorial analysis of variance yielded a significant nonlateralized mood by region interaction. Of nine individual regions compared, only inferior frontal cortex showed a significant difference in normalized regional metabolic rate between depressed and nondepressed patients. Metabolism in this region also distinguished patients with depressive symptoms from normal control subjects. Depressive symptoms in patients with complex partial seizures are associated with a bilateral reduction in inferior frontal glucose metabolism, compared with patients without depressive symptoms and normal control subjects. The frontal lobe hypometabolism observed in patients with depressions associated with epilepsy, Parkinson's disease, and primary affective disorder suggests that similar frontal lobe metabolic disturbances could underlie these conditions. PMID- 1596198 TI - White-matter hyperintensity and neuropsychological functions in dementia and healthy aging. AB - The relationship between quantitative measurements of brain white-matter hyperintensity (WMH), assessed by magnetic resonance imaging and neuropsychological functions, was explored in demented patients and healthy aged individuals with and without WMH in 12 brain regions. The prevalence of WMH was significantly higher in vascular dementia compared with Alzheimer's disease, especially in posterior periventricular regions. Results showed no difference in any neuropsychological measurement between healthy aged adults with and without WMH. The demented patients with WMH were more impaired in tests of visuoconstruction, attention, finger-motor speed, and latency of tactile identification of objects compared with patients without WMH. These impairments were related mainly to posterior periventricular WMH. There was no relationship between WMH and global cognitive functioning in the demented patients. The degree of WMH was related to age and blood pressure. The data suggest that specific regional WMH may result in specific neuropsychological impairments. PMID- 1596199 TI - Immunodiagnosis of neurocysticercosis. Disappointing performance of serology (enzyme-linked immunosorbent assay) in an unbiased sample of neurological patients. AB - To ascertain the reliability of serological diagnosis of neurocysticercosis in the everyday a priori situation of neurological consultation, the enzyme-linked immunosorbent assay test was used to predict the eventual diagnosis of neurocysticercosis in an unselected sample of 1064 consecutive neurological cases. Results showed 69% sensitivity and 71% specificity of the enzyme-linked immunosorbent assay test for the diagnosis of neurocysticercosis. In sharp contrast with publications that have proclaimed the excellent diagnostic performance of immunodiagnostic tests, our results suggest that identification of serum antibodies with standard enzyme-linked immunosorbent assay techniques is of little value when applied to a large and heterogeneous group of neurological patients in an endemic area of cysticercosis, and our results urge a reevaluation of currently used immunodiagnostic tests that are practiced in the serum of suspected cases. PMID- 1596200 TI - Sleep disturbance, depression, and lesion site in patients with multiple sclerosis. AB - We examined the prevalence of sleep problems in a sample of patients with mild but clinically definite multiple sclerosis (n = 143) and sought to determine whether there was a relationship between the presence of sleep complaints and the level of depression. As magnetic resonance imaging scans were available for a subsample of the patients with multiple sclerosis (n = 117), we also wanted to determine whether there was a relationship between the site of the lesion and the presence of sleep difficulties. The prevalence of sleep difficulties was three times higher in the patients with multiple sclerosis than the control group (25.2% vs 8.2%). Moreover, the presence of sleep complaints was associated with higher levels of depression. Three lesion sites that subserve supplemental motor areas were significantly related to the presence of sleep complaints. These findings suggest that, for some patients with MS, sleep disturbance and accompanying increases in depression may be a function of the lesion site resulting in nocturnal spasms. PMID- 1596201 TI - Vitamin B12 metabolism in multiple sclerosis. AB - We have previously described 10 patients with multiple sclerosis (MS) and unusual vitamin B12 deficiency. We have therefore studied vitamin B12 metabolism in 29 consecutive cases of MS, 17 neurological controls, and 31 normal subjects. Patients with MS had significantly lower serum vitamin B12 levels and significantly higher unsaturated R-binder capacities than neurological and normal controls, and they were significantly macrocytic compared with normal controls. Nine patients with MS had serum vitamin B12 levels less than 147 pmol/L and, in the absence of anemia, this subgroup was significantly macrocytic and had significantly lower red blood cell folate levels than neurological and normal controls. Nine patients with MS had raised plasma unsaturated R-binder capacities, including three patients with very high values. There is a significant association between MS and disturbed vitamin B12 metabolism. Vitamin B12 deficiency should always be looked for in patients with MS. The cause of the vitamin B12 disorder and the nature of the overlap with MS deserve further investigation. Coexisting vitamin B12 deficiency might aggravate MS or impair recovery from MS. PMID- 1596202 TI - The role of hypotension in septic encephalopathy following surgical procedures. AB - To study the risk factors for septic encephalopathy, we reviewed a consecutive series of 84 patients with septic syndrome and multiple-organ failure. Septic encephalopathy developed in 14 of these patients. Univariate analysis revealed that severe hypotension was significantly associated with the development of septic encephalopathy. In stepwise multiple logistic regression analysis, no other variable made a significant contribution in the presence of severe cardiovascular failure. Septic encephalopathy may be related to ischemic damage rather than to metabolic causes. PMID- 1596203 TI - Mortality from motor neuron disease in the province of Bologna, Italy, 1986 through 1988. AB - We performed a study on mortality from motor neuron disease in the province of Bologna, Italy, during the years 1986 through 1988. The study was based on death certificates from the Cancer Registry of the Province of Bologna. We verified death certificates for both false-positive and false-negative cases. The crude mortality rate was 1.93/100,000 population per year. The age and sex mortality rate, standardized on the Italian population, was 1.40/100,000 (95% confidence interval, 1.05 to 1.83). Our figures are higher than those previously reported both as the incidence and as mortality in Italy, but these data are similar to values that have been found in northern Europe and in North America. PMID- 1596204 TI - Effects of non-collagenous proteins on the formation of apatite in calcium beta glycerophosphate solutions. AB - The effects of the non-collagenous proteins; osteonectin, bone Gla protein and dentine phosphoprotein, on the formation of apatite were studied in calcium beta glycerophosphate solutions containing catalytic amounts of alkaline phosphatase under physiological conditions. In the system used, calcium phosphate precipitates de novo at levels of supersaturation precisely determined through the enzymatic hydrolysis of beta-glycerophosphate. At 1.7 mM of calcium beta glycerophosphate, calcium phosphate precipitated when inorganic phosphate accumulated to about 1.4 mM. In the presence of the proteins, however, a greater accumulation of inorganic phosphate was needed for calcium phosphate to precipitate, suggesting that a higher degree of supersaturation, though still a slight undersaturation with respect to dicalcium phosphate dihydrate, is required for calcium phosphate to precipitate in the presence of the proteins. At the same protein (micrograms/ml) concentration, dentine phosphoprotein was approximately four times as effective as bone Gla protein, which was about twice as effective as osteonectin in delaying precipitation. The proteins also retarded subsequent crystal growth, with apatite formed in the presence of the more inhibitory proteins having the smallest crystals, especially in width. PMID- 1596205 TI - The relationship between 48-h dental plaque accumulation in young human adults and the concentrations of hypothiocyanite, 'free' and 'total' lysozyme, lactoferrin and secretory immunoglobulin A in saliva. AB - Samples of resting and stimulated whole saliva and stimulated parotid saliva were collected from 40 young adults. One week later, after 48 h on a standardized diet without oral hygiene, all available plaque was collected for dry weighing. An inverse relationship was found between the 'free' lysozyme concentration in stimulated parotid saliva and plaque dry weight (r = -0.46, p less than 0.01). There were no other statistically significant correlation coefficients between concentrations of individual salivary constituents and plaque dry weight. However, cluster analysis of constituents in resting whole saliva revealed three groups of subjects with different salivary profiles, and in particular with different concentrations of both IgA and hypothiocyanite. Subsequent analysis revealed differences in plaque dry weight between the groups, demonstrating the potential biological significance of cluster membership based on salivary factors. PMID- 1596206 TI - Mitotic activity of cells in the fibrous zone of the rat mandibular condyle. AB - To investigate cell renewal in this fibrous zone, Wistar rats at 3 and 6 weeks of age were injected intraperitoneally with colchicine (1 mg/kg) three times, at 10:00, 13:00 and 16:00 h, and mitotic cells were examined after killing the rats at 18:00 h. Colchicine induced a significant increase in the number of arrested metaphases in the fibrous and the proliferating cell zone. The mitotic rates (per 1000 cells per h) in the fibrous zone at 3 weeks of age were 0.426 for the superficial layer and 0.266 for the deeper layer. These findings suggest that the fibrous zone of young rats grew with the proliferation of the cells within this zone. Age-associated histological changes in the fibrous zone were related to changes in mitotic rates within that zone. PMID- 1596207 TI - The effects of transforming growth factor-beta 1 on protein production by mouse embryonic palate mesenchymal cells in the presence or absence of serum. AB - Mouse embryonic palatal mesenchyme cells were cultured on a variety of substrata (plastic, on a collagen gel or within a collagen gel). On each substratum TGF beta 1 (1 ng/ml) inhibited cell proliferation. Cells cultured within a collagen gel had the lowest rate of proliferation, but were metabolically the most active in terms of incorporation of [3H]-proline into both collagenous and non collagenous proteins. TGF-beta 1, in the presence of 2.5% donor calf serum stimulated the production of fibronectin and the major collagen types I, III and V. However, in serum-free medium, TGF-beta 1 induced a large reduction in total collagen production, mainly due to an effect on type I collagen, whilst stimulating production of some non-collagenous proteins. Experiments involving combinations of TGF-beta 1 with other growth factors suggested that the different effects of TGF-beta 1 on collagen production, in the presence and absence of serum, may be due to an interaction with platelet-derived growth factor. PMID- 1596208 TI - Regional 31P magnetic resonance spectroscopy of exercising human masseter muscle. AB - Changes in fibre structure and function associated with exercise have been quantified ultrastructurally and biochemically in selected limb muscles, but the biochemical events associated with contraction are rarely studied in the human jaw muscles. Here, 31P NMR spectroscopy, or MRS, was used to examine the multipennate masseter in six adult men at rest and while performing isometric clenching exercises. NMR spectra were acquired from three locations within the muscle with a 2 x 3 cm, single-turn, copper receiver coil. The spectra, corrected for partial saturation effects, were quantified on the basis of relative peak area and position. The inorganic phosphate (Pi) to creatine phosphate (PCr) ratio (Pi/PCr), which has been shown to be indirectly related to the phosphate potential and hence the metabolic activity, as well as pH, were calculated for each site and exercise. The mean resting Pi/PCr ratio was greater for the deep part of the muscle than for the superficial and intermediate parts; these differences were significant to p less than 0.01. The mean pH was similar in all parts of the muscle at rest. During exercise, a significant increase in mean Pi/PCr was found in the superficial and intermediate parts of the muscle; both these differences were significant to p less than 0.05. An accompanying decrease in mean pH was observed in all parts of the muscle during exercise. In the superficial part, this decrease was significant to the p less than 0.05 level, and in the deep part, to the p less than 0.001 level. No significant differences were found for these measures between left and right molar clenching.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596209 TI - Correlations between an autoregressive model coefficient of the electromyogram of human jaw-closing muscles and maximum clenching time at the intercuspal position. AB - During maximum clenching in the intercuspal position, surface electromyograms of both masseters and both anterior temporales in seven healthy subjects with intact natural dentitions were sampled to generate a four-order, autoregressive model of the myoelectrical signal. The correlation coefficients and the linear regression between the model coefficients and the clenching time were calculated. The first order autoregressive coefficient had the greatest negative correlation on average. In this model the first-order coefficient relates to muscular fatigue and the slope of the regressive equation relates to the length of time the isometric contraction can be maintained. PMID- 1596210 TI - Dimensions of the temporal glenoid fossa and tooth wear in prehistoric human skeletons. AB - Both the mandibular condyle and the glenoid fossa remodel in response to changes in the dentition during life, although the precise relationship between teeth and joint is not clear. This study was undertaken to ascertain changes, if any, occurring in the glenoid fossae in skeletons with much tooth wear. In a collection of skulls from an excavation site on the South African coast, occlusal wear was measured using the scale devised by Molnar. The dimensions of the glenoid fossae were measured using a reflex microscope. Profiles of the glenoid fossa at right angles to a line through its medial and lateral poles provided estimates of the slope of the articular eminence in three places: centrally, and midway between this slope and each of the poles. The mediolateral profile gave an estimate of the height and gabling of the fossa. Central and lateral slope angles showed weak correlation with molar wear, and the medial but not the lateral angel was significantly different from the central. The fossa appears to remodel in response to patterns of forces generated during function, but compared to the condyle, is not as strongly influenced. This may be accounted for if the relative load-bearing areas of the condyle and fossa are considered. PMID- 1596211 TI - Effects of chronic ethanol consumption on the rat parotid gland. AB - Two-month-old Wistar rats ingested 10% ethanol for 12 months. Their parotid glands were then compared with those of normal controls by light microscopy. They had extensive ductal and acinar oncocytic transformation; numerous atypical acinar cells showed anisocytosis, polyploidism and hyperchromatism, features that were absent in controls. Oncocytosis and atypical acinar cells have been reported in 2-3-yr-old ('senile') Wistar rats. Thus, chronic alcohol ingestion may produce cellular features resembling those observed in the parotid gland of 'senile' Wistar rats. PMID- 1596212 TI - The use of capillary electrophoresis to identify cationic proteins in human parotid saliva. AB - Eight proteins, HRPs 1, 2, 3, 4, 5 and 6, lysozyme and histatin 6, are the major cationic components of the parotid salivas of normal healthy individuals. Histatins 2 and 4 appear to be further degradation products of the HRPs. Capillary electrophoresis separates all of these eight components, thus allowing future studies to correlate protein concentration with antimicrobial activity in health and disease. PMID- 1596213 TI - Increased mucin levels in submandibular saliva from mice following repeated isoproterenol treatment. AB - Mucin decreases with age in the submandibular glands of mice and can be restored by chronic administration of isoproterenol. Mice were given repeated injections of isoproterenol to determine if the increase of mucin in the submandibular gland leads to elevated levels of mucin in the submandibular saliva. Mucin was significantly elevated in both the gland and the saliva after isoproterenol. Gland contents of mucin and the concentration of mucin in their salivas were positively correlated for both the isoproterenol (p = 0.01) and the control group (p less than 0.01). PMID- 1596214 TI - Lyme disease? PMID- 1596215 TI - Acute, posterior, multifocal, placoid, pigment epitheliopathy and Lyme disease. PMID- 1596216 TI - Screening donor tissue: a safe and rational approach. PMID- 1596217 TI - Prism adaptation in acquired esotropia. PMID- 1596218 TI - Severe emotional response to eye trauma in a child: awareness and intervention. PMID- 1596220 TI - Proposed legislation to protect Medicare beneficiaries. PMID- 1596219 TI - Choroidal folds induced with diode endolaser. PMID- 1596221 TI - Eye injury resulting from violence. Research and prevention. PMID- 1596222 TI - Recognizing child abuse. PMID- 1596223 TI - Oil and gas on troubled waters. The proliferative vitreoretinopathy studies. PMID- 1596224 TI - Vitrectomy with silicone oil or sulfur hexafluoride gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 1. AB - Between September 1985 and September 1987, 101 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy but without prior vitrectomy were treated with vitrectomy and randomized to either a mixture of 20% sulfur hexafluoride gas and air or to 1000 centistokes of silicone oil. Between 50% and 60% of eyes that received silicone oil had visual acuity better than or equal to 5/200 compared with 30% to 40% of the eyes that received sulfur hexafluoride gas (P less than .05). Macula attachment was more frequent in eyes that received silicone oil than in those that received sulfur hexafluoride gas (80% vs 60%, P less than .05). Hypotony was more prevalent in eyes with a detached macula (40% to 50% for sulfur hexafluoride gas vs 25% to 30% for silicone oil) when compared with those with attached maculas (less than 5% for either modality). Keratopathy was more prevalent in eyes with detached maculas (about 55% to 60% for either modality) compared with eyes with attached maculas (25% to 30% for sulfur hexafluoride gas vs 10% to 15% for silicone oil). In a companion article, we show that these differences between a gas tamponade and silicone oil are not found for perfluoropropane gas. PMID- 1596225 TI - Vitrectomy with silicone oil or perfluoropropane gas in eyes with severe proliferative vitreoretinopathy: results of a randomized clinical trial. Silicone Study Report 2. AB - Between September 1987 and October 1990, 265 eyes with rhegmatogenous retinal detachment and severe (with a classification of at least C-3) proliferative vitreoretinopathy were treated with vitrectomy and randomized to treatment with perfluoropropane gas or silicone oil; 131 eyes had undergone no prior vitrectomy (group 1) while 134 eyes had undergone vitrectomy with intraocular gas tamponade (group 2). At the last examination, there were no differences between perfluoropropane gas and silicone oil in achieving visual acuity greater than or equal to 5/200 (43% vs 45% for group 1, 38% vs 33% for group 2) and complete posterior retinal reattachment (73% vs 64% for group 1, 73% vs 61% for group 2). For group 1 eyes followed up for at least 18 months, there was an advantage favoring perfluoropropane gas in achieving complete posterior retinal reattachment (83% vs 60% at 36 months, P = .045). The rates of reoperation and keratopathy were similar, while hypotony was more prevalent in eyes randomized to perfluoropropane gas (group 2). Regardless of tamponade, groups 1 and 2 had similar anatomic and visual success. However, hypotony was twice as prevalent in group 2 (perfluoropropane), and the prevalence of keratopathy increased with follow-up in group 2 (either tamponade). Either tamponade produced better results than those seen with sulfur hexafluoride gas (Silicone Study Report 1). PMID- 1596226 TI - Treatment of periorbital port-wine stains with the flashlamp-pumped pulsed dye laser. AB - Sixty-seven patients with periorbital port-wine stains were treated with the flashlamp-pumped pulsed dye laser at a wavelength of 577 or 585 nm and a pulse width of 450 microseconds. A retrospective analysis of the efficacy of this treatment was performed by qualitative and quantitative comparison of simultaneously projected pretreatment and post-treatment photographs and by comparison of photographs with a visual analog scale. These periorbital port-wine stains were treated with good-to-excellent results in 95% of the patients. As a result of treatment, macular (ie, nonhypertrophic) lesions, were lightened by an average of 80%. Neither scarring nor permanent pigmentary alteration was noted. Children of all ages were treated without adverse consequences, and the results were comparable to those of adults. The flashlamp-pumped pulsed dye laser treatment of periorbital port-wine stains is effective and safe in patients of all ages and should be considered the treatment of choice for flat and mildly hypertrophic lesions. PMID- 1596227 TI - Endophthalmitis caused by streptococcal species. AB - The medical records of 48 patients with culture-positive streptococcal endophthalmitis diagnosed between January 1977 and May 1990 were reviewed. The viridans group streptococci were isolated in 24 (50%) of the 48 cases, enterococci in 13 cases (27.1%), Streptococcus pneumoniae in six cases (12.5%), and beta-hemolytic streptococci in six (12.5%) of 48 cases. The clinical statuses of endophthalmitis cases by etiology were postoperative in 40 patients (83.3%), posttraumatic in six patients (12.5%), and miscellaneous in two patients (4.2%). Overall, 15 (31.2%) patients achieved 20/400 or better visual acuity. The streptococcal isolates demonstrated a 32.6% in vitro resistance to gentamicin sulfate, whereas all isolates were sensitive to vancomycin hydrochloride. The enterococci were often resistant to the cephalosporins, whereas the other streptococcal species were not. PMID- 1596228 TI - Postnatal development of the ciliary body and pars plana. A morphometric study in childhood. AB - The ciliary body of the human eye serves many vital functions and provides important access to the posterior segment of the globe in vitreoretinal surgery. Although embryogenesis and prenatal development of the ciliary body have been well documented, continuing development of the ciliary body during early childhood has not been studied extensively. We determined the lengths of the ciliary body and pars plana in 76 normal eyes of subjects who ranged in age from 1 week to 6 years. The ciliary body was found to be of substantial length soon after birth; it measured a mean of 3.06 mm nasally and 3.31 mm temporally. Three quarters of the final length of the ciliary body at adulthood was achieved by age 24 months. The growth of the ciliary body is discussed in relation to the growth of the eye. PMID- 1596229 TI - Fuchs' heterochromic iridocyclitis is not associated with ocular toxoplasmosis. AB - To analyze the association between Fuchs' heterochromic iridocyclitis (FHI) and toxoplasmosis, we performed ocular examinations and used various specific laboratory tests to establish a role for Toxoplasma gondii in the pathogenesis of FHI. Results were compared with those for other types of uveitis and healthy controls. Of the 88 patients with FHI, nine (10.2%) had toxoplasmosislike scars, but an association could not be proved by the indirect immunofluorescence antibody test or enzyme-linked immunosorbent assay, or by a test for cellular immunity to Toxoplasma antigen. Analysis of aqueous humor samples for Toxoplasma antibodies in patients with FHI also yielded negative results. On the basis of the negative results of these laboratory tests, we concluded that FHI is not associated with ocular toxoplasmosis. PMID- 1596230 TI - Glaucoma Hemifield Test. Automated visual field evaluation. AB - We have developed an algorithm, the Glaucoma Hemifield Test (GHT), for automated evaluation of single static threshold visual field test results in glaucoma. The GHT uses empirically determined limits of normality for up-down differences in the Statpac probability maps of the Humphrey Field Analyzer to detect localized visual field loss. It is also constructed to detect field loss that is symmetric around the horizontal meridian. Analysis is done in five corresponding pairs of sectors that are based on the normal anatomy of the retinal nerve fiber layer. Deviations from the age-corrected normal threshold in the most sensitive portions of the visual field are used to detect general reductions of sensitivity or abnormally high sensitivities. The GHT provides brief visual field evaluations printed on the field chart as plain text. The aim of this article is to describe the fundamentals of the analysis program and to provide clinical examples. PMID- 1596231 TI - Evaluation of methods for automated Hemifield analysis in perimetry. AB - A new aid to perimetric analysis, the Glaucoma Hemifield Test, primarily evaluates up-down differences in automated static visual field tests. We analyzed the visual fields of 163 eyes of 163 normal subjects and 77 eyes of 77 patients with glaucoma diagnosed on bases other than perimetry using the Glaucoma Hemifield Test and a similar, previously developed, hemifield analysis method. The performance of the Glaucoma Hemifield Test was compared with that of the earlier method and the differences in test design were evaluated individually. The Glaucoma Hemifield Test allowed significantly improved separation between the normal group and the group with glaucoma than did the earlier method. This improvement was due to an increase in sensitivity, and was associated with the use of test point significances instead of threshold values, and a large normal database alone in the determination of normal limits. PMID- 1596232 TI - Ocular trauma in the United States. Eye injuries resulting in hospitalization, 1984 through 1987. AB - The discharge rate for ocular trauma resulting in hospitalization and variations in rates between US census subdivisions were examined by using hospital discharge abstracts from the 1984 through 1987 National Hospital Discharge Surveys. The average annual rate of hospitalization with a principal diagnosis of ocular trauma was 13.2 per 100,000. The rate for any ocular trauma (principal or secondary diagnosis) was 29.1 per 100,000. Males were three times more likely to be hospitalized for a principal diagnosis of ocular trauma than females. Age specific rates for principal and secondary diagnoses of ocular trauma were distributed bimodally, with the highest peak in adolescents and young adults, and another peak among those 75 years or older. This study has begun the first step in profiling ocular trauma resulting in hospitalization in the United States. PMID- 1596234 TI - Penetrating eye injuries related to assault. The National Eye Trauma System Registry. AB - From 1985 to 1991, 648 cases of assault-related penetrating ocular injury were reported to the National Eye Trauma System Registry. We examined the circumstances surrounding and initial clinical findings related to this case series of injuries. Eighty-three percent of the patients were male. The median age was 28 years; 77% were younger than age 40 years, and 17% were younger than age 20 years. The ocular injury was part of multiple trauma in 34% of cases. There was evidence of alcohol and illicit drug use by at least 48% and 6% of the injured persons, respectively. Seventeen percent of the injuries involved powder or nonpowder firearms. Fists, glass fragments, metal rods or pipes, knives, and scissors were among the other objects causing injury. Posterior segment trauma, which occurred in 70% of cases, included vitreous hemorrhage (40% of cases), retinal detachment (11%), presence of intraocular foreign bodies (6%), and optic nerve damage (4%). The initial visual acuity after injury was hand motion or worse in 74% of the cases. Strategies to prevent such injuries focus on the origins of violence in general and are more difficult to devise than strategies to prevent eye injuries in other settings. Public health efforts to reduce the use of alcohol, drugs, and firearms may reduce the incidence of these injuries. PMID- 1596233 TI - Penetration eye injuries in the workplace. The National Eye Trauma System Registry. AB - Occupational eye injuries are common and preventable. Between 1985 and 1991, there were 635 work-related penetrating eye injuries among the 2939 cases (22%) reported to the National Eye Trauma System Registry by 48 collaborating centers in 28 states and Washington, DC. The median age of the injured workers was 30 years; 75% were younger than 40 years; and 97% were male. The commonest causes of injuries were projectiles (457 cases), sharp objects (166 cases), blunt objects (60 cases), and blasts (22 cases); these terms are not mutually exclusive. Specific objects causing injuries included nails, wire, screwdrivers, and other hand tools. There was evidence of alcohol use by at least 2% of the injured workers. When they were injured, 6% of the workers were wearing safety glasses; 3% were wearing nonsafety eyewear. Posterior segment trauma, which occurred in 63% of the cases, included vitreous hemorrhage (42%), intraocular foreign bodies (35%), and retinal detachment (10%). Hyphema occurred in 35% and traumatic cataract in 32% of the cases. Initial visual acuity after injury was hand motion or worse in 43% of the cases. National Eye Trauma System Registry data are useful to identify strategies to prevent occupational eye injuries such as wider use of safety glasses and improvement in engineering controls. PMID- 1596235 TI - Methylprednisolone ameliorates retinal photic injury in rats. AB - Since lipid peroxidation induced by oxygen free radicals is believed to play an important role in retinal photic injury and high doses of certain steroids have been demonstrated to inhibit lipid peroxidation, we evaluated the effect of high dose methylprednisolone sodium succinate on retinal injury inflicted by green light (490 to 580 nm, 160 to 180 foot-candles [1721.6 to 1936.8 lux]) for 24 hours in 36 rats. Animals received either intraperitoneal injections of the drug (80 mg/kg twice daily) or saline as a control, twice daily for 2 days, commencing with light exposure. The retinal photic injury was assessed 6 hours, 6 days, and 14 days after light exposure by light and electron microscopy, morphometric study of outer nuclear layer thickness and count of subretinal macrophages, and spectrophotometric measurement of rhodopsin. A beneficial effect of high-dose methylprednisolone was observed in retinal photic injury. PMID- 1596236 TI - Protective effects of flunarizine on ischemic injury in the rat retina. AB - Intracellular calcium overload has been implicated to be a major factor in triggering cell death after ischemic neuronal injury. We investigated the effects of flunarizine hydrochloride, a calcium-overload blocker, on pressure-induced retinal ischemia in a rat model. Retinal ischemia was induced in intraocular pressure to 110 mm Hg for 45 minutes. Two regimens of treatment with flunarizine were examined: (1) prophylactic treatment, in which flunarizine was administered before ischemia and in the early phase of reperfusion; and (2) postischemic treatment, in which flunarizine was administered only in the early phase of reperfusion. Injury was evaluated morphologically and morphometrically by measuring the thickness of the inner retinal layers on plastic-embedded retinal sections and by counting the retinal ganglion cells on retinal flat preparations. By morphologic and morphometric criteria, a significant but partial protection of the inner retinal layers was noted in the groups given either regimen. This protective effect of flunarizine suggests that elevated intracellular calcium concentration may play an important role in ischemic retinal injury. PMID- 1596238 TI - Purtscher's-like retinopathy associated with a cardiac aneurysm. PMID- 1596237 TI - Age-related loss of ciliary muscle mobility in the rhesus monkey. Role of the choroid. AB - Ciliary muscle topography was studied in rhesus monkey eyes (aged 6 to 29 years) bisected meridionally through cornea and optic nerve head. Half of each eye was incubated in atropine sulfate, the other in pilocarpine hydrochloride, and both were then processed for histologic study. Several ciliary muscle sections from the original cut margin and the middle of the half eyes were traced and compared quantitatively. In sections from the middle, where the attachments of the muscle were presumably intact, the pilocarpine effect on ciliary muscle topography was lost with age. In sections near the cut margin, where some of the posterior attachments were disrupted and the choroid had detached from the sclera, the pilocarpine effect persisted with age. These findings suggest that loss of ciliary muscle movement with age is caused by decreased compliance of its posterior attachment. PMID- 1596239 TI - Surgical management of advanced ocular adnexal amyloidosis. AB - Ocular adnexal amyloidosis is characterized by amyloid deposition within the deep connective tissue layers of the eyelids, conjunctiva, and anterior orbit. Management of advanced cases has traditionally been unsatisfactory, with either no surgery offered because of fear of hemorrhage or an en bloc resection performed of the entire involved area. We present two cases of advanced periorbital amyloidosis successfully managed by preserving the anatomic planes of the eyelids and meticulously debulking the deposits with a spooned curette. Lax eyelid tendons and aponeuroses were simultaneously repaired, and no sacrifice of eyelid tissues was necessary. One patient remained asymptomatic for 2 years after surgery before developing early reaccumulation in the lower eyelids. The other patient required additional eyelid debulking and ptosis revision 8 months after surgery, but was in stable condition at follow-up 2 years after surgery. This technique offers safe, easily repeatable, nondestructive treatment for advanced periocular amyloidosis. PMID- 1596240 TI - Effect of long-term ethanol administration on meprobamate level in brain of rat. AB - Effect of long-term ethanol administration on brain meprobamate concentration (BrMC) was investigated using rats. In ethanol-non-pretreated rats, the average ratio of the maximum BrMC (BrMCmax) to the maximum blood meprobamate concentration (BMCmax) was 0.75 when 25 mg/kg meprobamate were intraperitoneally administered to rats singly or together with ethanol (2 g/kg or 4 g/kg). By a pretreatment of the animals with ethanol at the daily dose of 0.4 g or 0.6 g for 25 days, the average ratio of BrMCmax to BMCmax was 0.91 when the same dose of meprobamate were given into the abdominal cavity. It was considered that by long term ethanol administration the permeability of blood-brain barrier to meprobamate might be accelerated, resulting in an increase in BrMC. PMID- 1596241 TI - Establishment of the ethanol-induced place preference in rats. AB - Ethanol failed to induce a place preference in both 15 and 50 min conditioning schedules in free-feeding and in food deprived rats. Acetaldehyde, the primary metabolic product of ethanol, induced a weak place aversion, dose-dependently. Ethanol combined with pyrazole (an alcohol dehydrogenase inhibitor) significantly induced a place preference in rats (ethanol; 300 mg/kg, i.p., pyrazole; 100 mg/kg, i.p.) in a 50 min conditioning schedule. The ethanol (300 mg/kg) combined with pyrazole (100 mg/kg)-induced place preference was antagonized or reduced by 5-HT3 antagonists (MDL72222, ICS205-930). These results suggest that a blockade of ethanol metabolism is very important for development of the ethanol-induced place preference in rats, and that the ethanol-induced place preference may be mediated by the mesolimbic dopamine system through 5-HT3 receptors. PMID- 1596242 TI - Drinking and driving in Singapore 1987 to 1989. AB - In the period 1987 to 1989 there were about 5,000 cases of fatal and injury sustained road traffic accidents, of which 2.3 to 3.0% were alcohol-related (Blood alcohol levels greater than the legal limit of 80 mg % ethanol). The offenders of alcohol-related accidents are mostly Chinese (greater than 79%), predominantly of the male gender (greater than 98%), and more often than not in the 30 to 40 age-range. The majority of the alcohol-related accidents took place between 8 p.m. to 4 a.m. (greater than 74%) under fine weather and light traffic. Rear-end, head-on and side-on collisions comprised over 60% of all the alcohol related accidents and losing control of vehicles about 30%. Drunken driving non accident cases for the same period showed a number of characteristics similar to those for alcohol-related accident cases. In Singapore motorcycle riders and pedestrians are more prone to road fatality than other road-user groups. International comparisons of road fatalities per 100,000 population gave Singapore one of the lowest accident rates (8.1 to 8.4) as compared to countries such as Australia, the United Kingdom, the United States, New Zealand, Canada and Japan. PMID- 1596243 TI - Measures against drunken driving in Germany. AB - The German authorities tend to reinforce the combat against drunken driving. Three of the countermeasures will undergo changes. The usual blood tests will be replaced by breath tests in the near future. The legal BAC limit will be reduced. And the limit above which a BAC is thought to indicate deviant drinking behaviour will be lowered. The changes may be desirable. But at the same time they are associated with analytical problems which demand a critical discussion. PMID- 1596244 TI - [Studies on ethanol absorption from the intestine--blood ethanol and acetaldehyde concentrations in the various vessels]. AB - We describe the concentration gradient of ethanol at different blood sampling sites of dogs dosed via the jejunal segment or intravenously, and the subsequent recovery of intestinal fluid from the jejunal segment. After laparotomy a 30 cm length of jejunal segment with intact vascular supply was isolated. Blood samples were collected from the portal vein, hepatic vein, aorta and inferior vena cava. A 17% ethanol solution was used for a small dose group (0.4 g/kg) and a 33% solution for a large dose group (0.8 g/kg). In the small dose and large dose groups administered the solution via the jejunal segment, ethanol concentration in the blood of the portal vein increased rapidly and the highest ethanol concentration was detected in the portal vein, followed, in descending order by the hepatic vein, aorta and inferior vena cava. The highest acetaldehyde concentration in blood was detected in the hepatic vein, followed by that in the aorta while the lowest was in the portal vein and inferior vena cava in both groups. Each concentration gradient corresponded in order to systemic circulatory order from the intestine (ethanol absorption site) for ethanol concentration, or from the liver (acetaldehyde formation area) for acetaldehyde concentration. There was no difference in ethanol concentration among the four sampling sites in the case of intravenous ethanol injection, but a gradation of acetaldehyde concentration similar to that in the jejunal segment dosed cases was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596245 TI - Effects of calcium antagonists on the cocaine- and methamphetamine-induced conditioned place preference. AB - The effects of calcium antagonists (nifedipine, flunaridine and diltiazem) on the cocaine- and methamphetamine-induced place preference were examined. Calcium antagonists alone induced neither place preference nor place aversion. Nifedipine markedly antagonized and flunarizine and diltiazem reduced the cocaine-induced place preference. The methamphetamine-induced place preference was reduced by nifedipine and diltiazem, but not by flunarizine. These results suggest the possibility that the cocaine-induced place preference is strongly influenced by dihydropyridine sensitive calcium channels, whereas the methamphetamine-induced place preference is not. PMID- 1596247 TI - Domestic violence: why does it happen? How can it be stopped? PMID- 1596246 TI - Sensitization to ambulation-increasing effects of cocaine after repeated administration in mice--roles of dose and interval of administration as well as experimental environments. AB - Effects of 5 subcutaneous injections of cocaine (COC) at 10, 20 or 40 mg/kg at intervals of 1 to 7 days were investigated by placing mice individually into tilting activity cages (20cm in diameter and 18 cm height). A progressive enhancement of the ambulation-increasing effect was noted for 3 to 4 hrs after each administration, showing marked sensitization (reverse tolerance). The enhancement of the effect progressed rapidly and the maximum sensitization was observed after the 3rd to 4th administration of 10 to 20 mg/kg at intervals of 3 to 7 days. The peak effect of the enhancement was of short duration. Sensitization lasted for at least one month. However, 40 mg/kg of COC produced stereotyped behaviors concurrent with preconvulsive signs which were also enhanced by serial administration. In contrast, pretreatment with COC in a narrow environment (glass jar, 5.5 cm in diameter and 15 cm height) did not cause the enhancement to the ambulation-increasing effect of the drug. Cross-sensitization was observed from COC to methamphetamine. PMID- 1596248 TI - Eat a live toad. PMID- 1596250 TI - How to read your Superannuation Statement. PMID- 1596249 TI - Nursing competencies: applying a competency based training system to nursing. Part two: Competencies across the nursing industry and gender issues. PMID- 1596251 TI - A baby dies every 18 seconds. PMID- 1596252 TI - The third age. Granny dumping. PMID- 1596253 TI - Private trouble or public issue? PMID- 1596255 TI - Differential heritability across levels of cognitive ability. AB - Differences in heritability and shared environmentality across levels of cognitive ability were assessed in a sample of 264 twin pairs tested at 1 year of age and in subsets tested at 2 and 3 years. Using an extension of the DF multiple regression methodology for analyzing twin data, no evidence was found for a linear or quadratic effect of level of cognitive ability on estimates of heritability or shared environmentality. PMID- 1596254 TI - Genetic and environmental influences on item response pattern scalability. AB - Numerous studies have examined how genetic and environmental factors determine individual differences on multi-item personality scales. Few studies, however, have examined how genes and the environment influence the route by which individuals obtain their scores on these scales. Specifically, on a multi-item test, dozens of item response patterns result in equivalent total scores, though some response patterns are more likely to be observed than others. For many scales it may be of interest to determine the genetic and environmental influences on the item response patterns, as well as the sum of the item responses. We discuss a latent trait measure of item response pattern scalability, called Zl (Levine and Drasgow, 1982), and investigate the properties of this index from a behavioral genetics perspective. Using a large sample of identical and fraternal twins from the Minnesota Twin Registry (Lykken et al., 1990), item response pattern scalability is shown to be moderately heritable. On the four scales of the Multidimensional Personality Questionnaire (Tellegen, 1982) that were investigated, approximately 20% of the variation in scalability was due to genetic diversity between subjects of our sample. Follow-up analyses, using a factor-analytically based, genotype-environment model of item response behavior, indicated that specific genetic and environmental factors play a substantial role in determining item response pattern variation. PMID- 1596256 TI - Maternal influences on infant hand-use during play with toys. AB - Infant hand-use preferences are related to mother's, but not father's, handedness. Since infants match mother's hand-use during toy play, maternal handedness can affect infant hand-use. Twenty-eight mother-infant pairs (14 left handed and 14 right-handed infants but all right-handed mothers) were videotaped while playing with six toys on the infant's 7-, 9-, and 11-month birthdays. Play was analyzed for five kinds of hand-use biasing situations, but maternal hand-use was the dominant influence. Infant matching of maternal hand-use increased with age and right-handed infants and female infants matched maternal hand-use more frequently. Concordance of hand-use preference between mother and infant seemed to account for both the matching and the stronger preferences of the right-handed compared to the left-handed infants. PMID- 1596257 TI - Differences in one-way active avoidance learning in mice of three inbred strains. AB - DBA/2J, C57BL/6J, and C3H/HeJ mice were given 10 one-way avoidance training trials per day, using an unconditioned stimulus intensity that provided equivalent motivation for learning to mice of all three strains, and were found to differ in their abilities to learn and retain the response. DBA/2J mice acquired the response in fewer days than did the mice of the other two strains, although C57BL/6J mice eventually reached a level of performance similar to that of DBA/2J mice. Both the rate of acquisition and the level at which avoidance performance stabilized were significantly lower in C3H/HeJ, than in DBA/2J or C57BL/6J, mice. In addition, DBA/2J mice showed a significantly greater task retention from one testing day to the next than did C57BL/6J or C3H/HeJ mice. PMID- 1596258 TI - Simulated twin data on substance abuse. AB - Twin data were simulated for use of a new illegal substance. The twin cohort was "measured" yearly at 10 time intervals during the diffusion of the substance throughout the nation. The models used to generate the data are discussed. PMID- 1596259 TI - The relationship between age at first drug use and teenage drug use liability. AB - Our analyses of Carey's (1992) simulated data set of substance abuse in a cohort of adolescent twins were aimed at answering the question What is the relationship between age at first drug use and EVER having used drugs (i.e., teenage drug use liability)? Three analytic methods were used to determine whether age at first drug use was (1) a "perfect" index of drug use liability, (2) correlated in relatives but conditionally independent of drug use liability, or (3) causally influenced by drug use liability and by factors independent of liability. The analytic methods included nonmetric multidimensional scaling, multifactorial threshold model-fitting to contingency tables, and pedigree-based likelihood formulations for the raw data. All approaches indicated that age at first drug use was a perfect index of drug use liability. Further, model-fitting results indicated that only shared environmental factors accounted for twin similarity in the onset and timing of drug use. We discuss the limitations of each of the analytic methods and integrate our findings with the true model used in Carey's simulation. PMID- 1596260 TI - Likelihood-based analyses of longitudinal twin and family data: experiences with pedigree-based approaches. AB - Substantial progress has been made recently in analyses of longitudinal twin and family data, principally for two reasons. The first is the continuing development of more refined models for describing longitudinal data; the second is the widespread availability of analytic methods (e.g. LISREL) with which to implement these models. Computational restrictions have limited likelihood-based analyses of longitudinal genetic data to analyses of covariance matrices or mean squares; however, advances in computer technology now make it feasible to conduct likelihood analyses of longitudinal pedigree data. We consider potential advantages of using pedigree-based methods. Our initial experiences with the application of these methods to simulated twin data, using the FISHER (Lange, K.L., et al., Genet. Epidemiol. 5:471, 1988) quantitative genetics package, are discussed, with particular attention to practical details such as running times on several computers. Preliminary results of the pedigree-based analyses, including robust estimation methods, convincingly demonstrate the failure of methods assuming the multivariate normal distribution for simulated twin data provided by Carey (this issue). PMID- 1596261 TI - The Colorado Adoption Project: general cognitive ability and height data at ages 1 to 4 years. PMID- 1596262 TI - Quantitative genetic analysis of IQ development in young children: multivariate multiple regression with orthogonal polynomials. AB - The study of psychological development has recently benefited from innovative analytic methods for estimating and examining the correlates of individual growth curves. These methods are more consistent with a conceptualization of development as an ongoing, continuous process, rather than as increases or decreases in a trait between two discrete time points. Recent developmental behavior genetic models have focused on continuity and change in the genetic and environmental influences underlying phenotypes. In contrast, we present a model for genetic and environmental influences on phenotypic development per se. In this model, we adapted multiple regression methods developed for twin designs (DeFries and Fulker, 1985) to a parent-offspring adoption design and to a multivariate framework in which repeated measurements are decomposed into orthogonal polynomial trends. We applied these analyses to the development of IQ during infancy and early childhood using parent-offspring data from adoptive and nonadoptive families in the Colorado Adoption Project. The results suggested familial environmental influences on children's mean IQ for ages 1-4 but environmental influences specific to fathers' cognitive ability on children's IQ development. We also discuss advantages and disadvantages of the multivariate multiple regression method for studying genetic and environmental influences on development. PMID- 1596263 TI - Using EQS for a simple analysis of the Colorado Adoption Project data on height and intelligence. AB - Simple models in the general spirit of Coon et al. (1990) are fit to the Colorado Adoption Project height and intelligence data as the second step in a two-step process. In the first step, over-time data on height and IQ are reduced to level and slope parameters. In the second, these are incorporated in path models along with parental data and fitted using EQS in a multiple-group design. Some comparisons are made between EQS and LISREL for this kind of modeling. PMID- 1596264 TI - The Dutch Twin Register: growth data on weight and height. AB - As part of a longitudinal developmental study of newborn and young Dutch twins, data on weight and height are collected. Birth weight and height are available for 3275 pairs; data on growth, for 1390 pairs. PMID- 1596265 TI - Biometrical analysis of individual growth curves. AB - Longitudinal data for height (length) between birth and 2 years of age were examined for 690 Dutch Registry twin pairs. A two-stage analysis was performed, where individual growth curves were first fit to available data for each subject using a linear multiple regression procedure and estimated individual growth curve parameters were then subjected to multivariate biometrical analysis. Quadratic polynomial curves were found to adequately represent observed growth patterns for the majority of cases (median R2 = .98). A specific scalar model of sex limitation best characterized individual variation in growth curve parameters. That is, there was significantly greater genetic variation for boys than for girls in both the predicted length and rate of growth at 1 year of age and the amount of deceleration in individual growth curves across age. PMID- 1596266 TI - [Fine structure of the facial nerve nucleus of the domestic hen]. AB - The facial nucleus of the domestic hen is composed of a dorsal, intermediate, and ventral portion. The dorsal and intermediate one consist of medium-sized and rare small polygonal and oval neurons. The ventral subnucleus shows medium-sized and large neurons. Electronmicroscopically, the latter exhibit numerous Nissl bodies with short cisterns and a lot of polysomes. The small neurons comprise few but large Nissl bodies with long cisterns of the rough endoplasmic reticulum. According to the shape of synaptic vesicles and the number of mitochondria three distinct types of synapses can be distinguished. PMID- 1596267 TI - [Clinical chemistry in leukosis of horses (review)]. AB - Clinicopathological aspects of equine leukosis are discussed in a review. Among various other findings, only hypercalcaemia accompanied by paraneoplastic syndrome in the course of equine leukosis, increased values of alkaline phosphatase as usual in tumorous diseases, and hypalbuminaemia and hypergammaglobulinaemia in mesentric and intestinal forms of equine leukosis seem to have some diagnostic and pathogenetic significance. Changed values of further parameters are more or less non-specific concomitant signs, indicating that other organs or organ systems have been affected. However, in case of suspicion of equine leukosis furthermore clinicopathological investigations are recommended particularly for differential-diagnostic reasons. PMID- 1596269 TI - Evolution and development. PMID- 1596268 TI - [Neural regulation of food absorption--review]. AB - The periodical food intake (discrete meals) demands a control system, which includes signals for hunger and satiety. Satiety and hunger change with the absorptive and postabsorptive state of the delivery of nutrients to the organism. The brain areas involved in the regulation of food intake receive informations from three sources: periphery, environment and memory. Hypothalamic structures and pathways of neurotransmitters are considered especially. Beside these, the limbic structures are mainly responsible for the development of motivated feeding behaviour. Disturbances in the regulation of feeding behaviour are prone to cause obesity and anorexia nervosa. PMID- 1596270 TI - Direct-developing sea urchins and the evolutionary reorganization of early development. AB - The evolution of development can be made accessible to study by exploiting closely related species that exhibit distinct ontogenies. The direct-developing sea urchin Heliocidaris erythrogramma is closely related to indirect-developing sea urchins that develop via a feeding larval stage. Superficial consideration would suggest that simple heterochronies resulting in loss of larval features and acceleration of adult features could explain the substitution of direct for indirect development. However, our experiments show that early development has in fact been extensively remodeled, with modified localization of maternal determinants coupled with dissociation of cell cleavage from axis formation resulting in novel patterns of cell lineage differentiation and fate map. Gene expression has undergone concomitant changes. PMID- 1596271 TI - Evolution of alternate modes of development in ascidians. AB - Ascidians have evolved alternate modes of development in which the conventional tadpole larva is remodeled or eliminated. Adultation, the precocious development of adult features in the larval head, is caused by superimposing the larval and adult differentiation programs. Caudalization, the addition of muscle cells to the larval tail, is caused by enhancing muscle induction or increasing the number of muscle cell divisions before terminal differentiation. Adultation and caudalization are correlated with increased egg size, suggesting dependence on maternal processes. Anural development, the elimination of the larval stage, is caused by maternal and zygotic events resulting in abbreviation and deletion of larval developmental programs. An example of a maternal change in anural species is the modification of the egg cytoskeleton during oogenesis, whereas a zygotic change may involve altered cell interactions during embryogenesis. Interspecific hybridization experiments suggest that some aspects of anural development may be caused by loss-of-function mutations. The dissociation of developmental programs is a key process in changing the mode of development in ascidians. PMID- 1596272 TI - Maize mutants and variants altering developmental time and their heterochronic interactions. AB - It is useful to envision two fundamentally different ways by which the timing of plant development is regulated: developmental stage-transition mechanisms and time-to-flowering mechanisms. The existence of both mechanisms is indicated by the behavior of various mutants. Shoot stage transitions are defined by dominant mutants representing at least four different genes; each mutant retards transitions from juvenile shoot stages to more adult shoot stages. In addition, dominant leaf stage-transition mutants in at least seven different genes have similar phenotypes, but the leaf rather than the shoot is the focus (and at least two of these genes encode homeodomain proteins.) One mutant, Hairy sheath frayed 1-O (Hsf1-O) simultaneously affects shoot and leaf; this mutant's behavior initiated our interest in plant heterochronism. The second type of timekeeping involves time-to-flowering. As with most plant but not animal species, cultivars of the maize species vary greatly for the time-to-flowering quantitative trait: between 6 and 14 weeks is common. It is via the 'slipping time frames' interaction that takes place between stage-transition mutants and time-to flowering genetic backgrounds that unexpected and radical phenotypes occur. We see a reservoir of previously unsuspected morphological possibilities among the few heterochronic genotypes we have constructed, possibilities that may mimic the sort of variation needed to fuel macroevolution without having to posit (as done by Goldschmidt) any special macromutational mechanisms. PMID- 1596273 TI - Transgenic animal studies on the evolution of genetic regulatory circuitries. AB - The ability to transfer genes from one species to another provides a powerful method to study genetic regulatory differences between species in a homogeneous genetic background. A survey of several transgenic animal experiments indicates that the vast majority of regulatory differences observed between species are due to differences in the cis-acting elements associated with the genes under study. A corollary is that in almost all cases the host species provides the necessary regulatory proteins for expression of the transgenes in specific tissues in which the endogenous homolog is not expressed. Although the details of the cis-acting differences are unknown for most cases, it appears that these differences may consist of the acquisition or loss of unique elements or subtle variation of conserved elements. It is unknown whether much of this variation is directly related to adaptive evolution. The identification of the promoter/enhancer elements responsible for these differences is an important first step in examining the functional significance of this variation. PMID- 1596274 TI - Genetic sex determination mechanisms and evolution. AB - Different animal groups exhibit a surprisingly diversity of sex determination systems. Moreover, even systems that are superficially similar may utilize different underlying mechanisms. This diversity is illustrated by a comparison of sex determination in three well-studied model organisms: the fruitfly Drosophila melanogaster, the nematode Caenorhabditis elegans, and the mouse. All three animals exhibit male heterogamety, extensive sexual dimorphism and sex chromosome dosage compensation, yet the molecular and cellular processes involved are now known to be quite unrelated. The similarities must have arisen by convergent evolution. Studies of sex determination demonstrate that evolution can produce a variety of solutions to the same basic problems in development. PMID- 1596275 TI - Redundancies, development and the flow of information. AB - There is increasing evidence for the wide-spread existence of functionally redundant genetic pathways in developmental processes. However, both their significance and manner of evolution are still matters of debate. I will argue here that redundancy of gene actions may, in fact, be a necessary requirement for the development and evolution of complex life forms. One can view development as a process that transmits information from the egg to the adult organism. Transmission of information is, however, always an error-prone process, which can only be safeguarded by including redundancies in the message. Molecular examples for well analysed redundant processes indicate that redundancies may best be understood within a conceptual framework of overlaps between different gene functions. PMID- 1596276 TI - Ontogeny and phylogeny--revisited and reunited. PMID- 1596277 TI - Immunological properties of vitamin D analogues and metabolites. AB - This commentary has attempted to describe some of the new aspects of our knowledge of the immunological properties of 1 alpha,25(OH)2D3, the physiologically active metabolite of vitamin D3, and its new analogues. These analogues will, in the future, serve as tools to increase our understanding of the role of vitamin D in immunobiology, not only in basal research but also, hopefully, in the therapy of immune-mediated diseases. PMID- 1596278 TI - Polar metabolites of dihydrotachysterol3 in the rat. Comparison with in vitro metabolites of 1 alpha,25-dihydroxydihydrotachysterol3. AB - The metabolism of 25-hydroxydihydrotachysterol3 (25-OH-DHT3) to more polar metabolites was investigated in vivo in the rat and compared with the in vitro metabolism of 1 alpha,25-dihydroxy-DHT3 (1 alpha,25-(OH)2DHT3) in the osteosarcoma cell line UMR 106. Rats were given 2 mg of DHT3 in divided doses at 0 and 6 hr. Plasma was collected 24 hr after the initial dose, extracted, separated, and polar metabolites purified by HPLC. A number of polar metabolites were formed in vivo with mass spectrometric characteristics which suggested that they were derived from a previously isolated metabolite of 25-OH-DHT3, T3/H. Of these, four were isolated and identified as 24-oxo-T3/H, 24-hydroxy-T3/H, 26 hydroxy-T3/H and the 26,23-lactone of T3/H. In view of the identification of T3/H as a mixture of 1 alpha- and 1 beta-hydroxylated 25-OH-DHT3, osteosarcoma cells (UMR 106) were incubated with chemically synthesized 1 alpha,25-(OH)2DHT3 in an attempt to determine from which component of the T3/H mixture these metabolites were derived. Again, more polar metabolites were formed and five of these were isolated by lipid extraction, purified by HPLC and identified as 24-oxo-1 alpha,25-(OH)2DHT3, 1 alpha,23,25-(OH)3DHT3, 24-oxo-1 alpha,23,25-(OH)3DHT3, 1 alpha,24,25-(OH)3DHT3 and 1 alpha,25,26-(OH)3DHT3. Three of the in vitro metabolites were similar to those found in rat plasma but only two of these metabolites were available in sufficient amounts to allow comparison. The chromatographic characteristics, using HPLC and gas chromatography, of these two pairs of metabolites (24-oxo and 24-hydroxy) were examined and it was demonstrated that they were not the same. It is therefore suggested that the polar metabolites formed in vivo are in fact metabolites of the T3/Hb component (1 beta,25-(OH)2DHT3) rather than the T3/Ha component (1 alpha,25-(OH)2DHT3). Supporting evidence for this suggestion was obtained when a small quantity of 1 beta,25-(OH)2DHT3, obtained from chemically synthesized 1 beta-OH-DHT3 by incubation with Hep 3B cells, was further incubated in the osteosarcoma UMR 106 system. Preliminary studies indicated that the putative 24-oxo and 24-hydroxy metabolites formed from 1 beta,25-(OH)2DHT3 had chromatographic and mass spectral properties almost indistinguishable from those of corresponding metabolites of T3/H formed in vivo. All the metabolites formed in vivo and in vitro are components of two metabolic pathways described previously for 25-hydroxyvitamin D3 and also for 25-OH-DHT3. PMID- 1596280 TI - Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities in bovine and rabbit tissues. AB - The tissue distributions of debrisoquine 4-monooxygenase and bufuralol 1' monooxygenase activities in microsomes from bovine and rabbit tissues were analysed. Debrisoquine 4-monooxygenase and bufuralol 1'-monooxygenase activities were found in liver, and at low levels in cerebral cortex, kidney cortex, lung, small intestine and spleen. Other tissues, such as kidney medulla, adrenocortex, adrenomedulla, blood vessels, thyroid gland, heart, ovary, uterus and testis, showed low levels of bufuralol 1'-monooxygenase activity but not detectable debrisoquine 4-monooxygenase activity. The bufuralol/debrisoquine monooxygenase activity ratios were higher in kidney and lung, and lower in cerebral cortex and spleen than in liver. Both monooxygenase activities in several bovine tissues including liver were inhibited strongly by phenylisocyanide (0.1 mM) and quinidine (0.5 mM), moderately by metyrapone (1 mM), and not at all by KCN (1 mM). NaN3 (5 mM) and sodium cholate (0.5% w/v) inhibited debrisoquine 4 monooxygenase activity strongly and moderately, but bufuralol 1'-monooxygenase activity moderately and strongly, respectively. No effect of a hydroxyl radical scavenger or of superoxide dismutase on either monooxygenase activity was observed. It was concluded from these results, as well as the NADPH dependency of the reactions, that the two monooxygenase reactions observed in these tissues were catalysed by cytochrome P450s. PMID- 1596279 TI - Decrease in the content of cytochrome P450IIE by fasting in liver microsomes of house musk shrew (Suncus murinus). AB - The effects of fasting on hepatic cytochrome P450 in the mature male house musk shrew, Suncus murinus (suncus), were studied by Western blot analyses and enzyme assays. The content of P450IIE protein was decreased, by fasting, to 24% of the control level in contrast to the results with rats, in which P450IIE protein was increased to 172% by fasting. These changes reflected on catalytic activities, such as aniline hydroxylase and N-nitrosodimethylamine demethylase activities, which were decreased to about 45% and 28%, respectively, of the control levels by fasting, while in fasting rats, the catalytic activities of these enzymes were 2 3-fold higher than in controls. PMID- 1596282 TI - Purification and characterization of glucocorticoid-inducible steroid esterase in rat hepatic microsomes. AB - A steroid esterase hydrolysing methylprednisolone 21-hemisuccinate was purified from the hepatic microsomes of rats treated with dexamethasone, a potent inducer of the esterase. The enzyme was solubilized by Lubrol WX and purified up to 30 fold over the microsomal fraction by ammonium sulfate fractionation and successive chromatographies with gel permeation, DEAE-cellulose and hydroxylapatite. The steroid esterase thus purified showed a single band and a molecular mass of 58 kDa on SDS-polyacrylamide gel electrophoregram. The enzyme appears likely to exist as two interconvertible forms, which can be distinguished by pI values, pI 4.9 and 5.1. The enzyme was completely inhibited by organic phosphates, indicating that it can be classed as a carboxylesterase (EC 3.1.1.1). Both negatively charged and uncharged esters of several steroids (methylprednisolone, hydrocortisone, deoxycorticosterone and dehydrotestosterone) as well as various non-steroidal esters including 4-nitrophenyl esters were hydrolysed by the enzyme, but none of the amides were substrates. The enzyme showed higher activity with increasing lipophilicity of the substrates. It is noticeable that the optimum pH for charged esters was 5.5, whereas the highest activity was observed around pH 7-8 for uncharged esters. When methylprednisolone 21-hemisuccinate (one of the charged esters) was used as substrate, the Km value was 2.8 mM and Vmax was 59.3 mumol/mg protein for 1 min at the optimum pH of 5.5. Regarding the methyl ester of methylprednisolone 21-hemisuccinate, Km and Vmax values were 1.8 mM and 193 mumol/mg protein/min, respectively, at the optimum pH of 7.0. On the basis of these results, the enzyme is most likely a carboxylesterase. PMID- 1596281 TI - Specific induction by glucocorticoids of steroid esterase in rat hepatic microsomes and its release into serum. AB - Steroid esterase hydrolysing methylprednisolone 21-hemisuccinate was induced specifically and markedly in hepatic microsomes and serum of rats by various glucocorticoids. Among the glucocorticoids examined, dexamethasone and betamethasone showed the highest potency to induce the hepatic steroid esterase, the induction ratio being 32 and 33 times higher than the basal level (about 160 mU/g liver), respectively. Steroid esterase in the serum was induced greatly by fluocinolone acetonide and betamethasone to 92 and 79 times of the basal level of about 16 mU/mL, respectively, followed by dexamethasone and methylprednisolone. When dexamethasone was given to rats, the enzyme in other tissues except for duodenum and small intestine (of which activity was lowered to 50% of the basal level) was also elevated, but the induction ratio was much lower than that in the liver and serum. The induction of the steroid esterase is probably due to stimulation of de novo synthesis of the enzyme by glucocorticoids, because the elevation of esterase activity was inhibited by treatment with cycloheximide (a translation inhibitor) and actinomycin D (a transcription inhibitor), and about 4 and 10-hr lag time was observed before the elevation of esterase activity in liver and serum, respectively. Coupled with these observations the following results indicate that the steroid esterase in serum is probably synthesized in the liver and subsequently released into the blood via the Golgi apparatus: (1) when the liver of rats treated with dexamethasone was subjected to perfusion with a recycling system, significant amounts of steroid esterase were released into the perfusate; (2) anti-hepatic esterase antibody inhibited the steroid esterase activity not only in the liver but also in serum; and (3) monensin, which prevents the secretion of various kinds of secretory proteins by disrupting the function of the Golgi apparatus, inhibited the elevation of the steroid esterase activity in serum by dexamethasone but did not affect the induction in liver. PMID- 1596283 TI - Mefloquine metabolism by human liver microsomes. Effect of other antimalarial drugs. AB - A number of drugs have been studied for their effect on the metabolism of the antimalarial drug mefloquine by human liver microsomes (N = 6) in vitro. The only metabolite generated was identified as carboxymefloquine by co-chromatography with the authentic standard. Ketoconazole caused marked inhibition of carboxymefloquine formation with IC50 and Ki values of 7.5 and 11.2 microM, respectively. The inhibition of ketoconazole, a known inhibitor of cytochrome P450 isozymes, and the dependency of metabolite formation on the presence of NADPH indicated that cytochrome P450 isozyme(s) catalysed metabolite production. Of compounds actually or likely to be coadministered with mefloquine to malaria patients only primaquine and quinine produced marked inhibition (IC50, 17.5 and 122 microM; Ki, 8.6 and 28.5 microM, respectively). However, despite these in vitro data with primaquine, clinical studies have failed to show any significant effect of single dose primaquine on the pharmacokinetics of mefloquine. With quinine, because peak plasma concentrations are very close to the Ki value, there is likely to be inhibition of mefloquine metabolism in patients receiving both drugs. Sulfadoxine, artemether, artesunate and tetracycline did not significantly inhibit carboxymefloquine formation. PMID- 1596284 TI - Hepatocyte toxicity of mechlorethamine and other alkylating anticancer drugs. Role of lipid peroxidation. AB - The alkylating anticancer drugs, mechlorethamine (HN2), chlorambucil, cyclophosphamide, carmustine and lomustine readily induced cytotoxicity in isolated rat hepatocytes. Hepatocyte glutathione (GSH) was depleted rapidly following addition of the drugs. Lipid peroxidation ensued following GSH depletion and before cytotoxicity occurred. Furthermore, cytotoxicity was delayed by the antioxidants butylated hydroxyanisole (BHA) and alpha-tocopherol, the ferric iron chelator desferoxamine or the radical trap 4-hydroxy-2,2,6,6 tetramethylpiperidine-N-oxyl (TEMPO) even when added 10 min later. HN2 was much less toxic to hepatocytes under nitrogen and caused much less lipid peroxidation than under aerobic conditions. Cytotoxicity induced by HN2 was also prevented by choline, suggesting that a choline carrier is responsible for HN2 uptake in the hepatocytes. Various sulfur compounds acted as antidotes for HN2 cytotoxicity. Thiosulfate was still effective when added 30 min after HN2. Depletion of GSH in the hepatocytes markedly increased their susceptibility to HN2. However, BHA, desferoxamine or TEMPO protected these hepatocytes from HN2. This suggests that antioxidants could prove useful in preventing the increased risk of hepatotoxicity if GSH-depleting agents are used to overcome tumor resistance to nitrogen mustards. PMID- 1596285 TI - Reduction of cardiovascular and thyroxine-suppressing activities of L-T3 by liver targeting with cholic acid. AB - This study was designed to determine whether the conjugation product of L-T3 with cholic acid would result in a liver-targeted compound (CGH 509A) with hypocholesterolemic (HC) activity significantly dissociable from cardiovascular (CV) and thyroxine-suppressing (TS) effects normally observed with thyroid hormone. Evaluation of HC activity in lipemic rats showed that CGH 509A was 6 times less potent than L-T3 with ED25 values estimated at 150 and 25 nmol/kg, respectively. CV function measured as changes in atrial rate, atrial tension and heart weight was determined in euthyroid rats. CGH 509A was at least 64 times less cardio-stimulant than L-T3 with minimum effective doses estimated at 2350 and 37 nmol/kg, respectively. TS activity was assessed in euthyroid rats as the potency of any compound to reduce plasma T4 levels. CGH 509A was 50 times less potent than-L-T3 with ED50 values estimated at 900 and 18 nmol/kg, respectively. From these results, it is clear that, while L-T3 was equally potent on HC, CV and TS activities, the HC potency of CGH 509A was at least 15 and 6 times greater than its CV and TS potencies, respectively. PMID- 1596287 TI - Transport and metabolism of cyclosporine in isolated rat hepatocytes. The effects of lipids. AB - The effects of lipids on the uptake and metabolism of cyclosporine (CyA) were investigated in isolated rat hepatocytes. In the absence of lipids, CyA was rapidly taken up (reaching apparent steady state within 5 min) and highly associated with the cells (more than 80%). The CyA uptake was concentration independent over the concentration range studied (0.6 to 11.2 micrograms/mL). Metabolism, however, was relatively slow and saturable. Except for cholesterol (at concentrations up to 15.5 mM), all lipids tested [oleic acid; low density lipoproteins (LDL); and high density lipoproteins (HDL)] reduced CyA cell uptake as well as its metabolism in a concentration-dependent manner. The effects of LDL were much more pronounced when compared to those of HDL and oleic acid. At an LDL concentration of 1 microM, drug uptake, indicated by the cell-associated concentration at steady state, was about 49% of the control value, while CyA metabolism was inhibited completely. Drug uptake of about 82 and 91% and CyA disappearance of 75 and 68% of the relevant control values were observed with HDL and oleic acid at concentrations of 10 microM and 0.7 mM, respectively. Apparently, lipids decreased CyA metabolism by reducing the concentration of CyA available for transport into the cells. These findings further support the suggestion of an important role for plasma lipids in the disposition of CyA. PMID- 1596286 TI - Cocaethylene hepatotoxicity in mice. AB - Cocaethylene is a novel metabolite of cocaine formed in the presence of ethanol. When administered to ICR male mice in dosages ranging from 10 to 50 mg/kg, i.p., cocaethylene was found to produce dose-dependent hepatic necrosis in the midlobular zone (zone 2). Severity of the lesion was maximal 12-24 hr after administration. A transient but significant decrease in hepatic glutathione content was observed 1 hr after cocaethylene administration. Pretreatment with the cytochrome P450 inhibitors cimetidine (200 mg/kg, i.p., in divided doses) or SKF 525A (50 mg/kg, i.p.) diminished toxicity. Pretreatment of mice with the esterase inhibitor diazinon (10 mg/kg, i.p.) increased cocaethylene hepatotoxicity, as did pretreatment with the cytochrome P450 inducing agents phenobarbital (80 mg/kg/day, i.p., for 3 days) or beta-naphthoflavone (40 mg/kg/day, i.p., for 3 days). Phenobarbital pretreatment also caused a shift in the morphologic site of necrosis from midzonal to peripheral lobular (zone 1) regions. The type of hepatic lesion produced by cocaethylene, its morphologic distribution (including the shift with phenobarbital treatment), the potency of cocaethylene in producing this effect, and the apparent requirement of oxidative metabolism for hepatoxicity were all remarkably similar to observations with its parent compound, cocaine, in this and earlier studies. This suggests that these compounds produce liver toxicity through the same or similar mechanisms. PMID- 1596288 TI - Binding of [3H]bryostatin 4 to protein kinase C. AB - The bryostatins represent a unique class of activators of protein kinase C (PKC) which induce only a subset of the responses typical of the phorbol esters and block those responses to the phorbol esters which they themselves do not induce. To better understand the interaction of the bryostatins with PKC, we have synthesized [26-3H]bryostatin 4 and characterized its binding to PKC. [3H]Bryostatin 4 and [3H]phorbol 12,13-dibutyrate ([3H]PDBu) differed markedly in their binding to PKC reconstituted with phosphatidylserine (PS). The binding affinity of [3H]bryostatin 4 under these conditions was too high to measure and the rate of release of bound bryostatin was much slower than that of the phorbol esters, with a half-time of several hours. These properties caused bryostatin 1 to appear to inhibit [3H]PDBu binding under these conditions in a non-competitive fashion. Both the high potency and the slow rate of release of the bryostatins may contribute to their unique pattern of biological activity. By reconstituting PKC in a mixture of 1.5% Triton X-100:0.3% PS, we were able to establish reversible conditions for [3H]bryostatin 4 binding. Under these latter conditions, binding of [3H]bryostatin 4 was competitively inhibited by PDBu, consistent with both the bryostatin and phorbol esters binding to PKC in a qualitatively similar fashion. Binding affinities to PKC isozymes alpha, beta, and gamma were compared and little difference was found, suggesting that differential recognition by these isozymes does not account for the unique biological activity of the bryostatins. PMID- 1596289 TI - Kinetic characteristics of ICI D1694: a quinazoline antifolate which inhibits thymidylate synthase. AB - The thymidylate synthase (TS) inhibitor ICI D1694 (N-(5-[N-(3,4-dihydro-2-methyl 4-oxoquinazolin-6-ylmethyl)-N -methylamino]-2 - thenoyl)-S-glutamic acid) is a structural analogue of the substrate N5,N10-methylenetetrahydrofolate (5,10 CH2FH4) and is currently under clinical evaluation as a treatment for cancer. The compound is shown here to be a mixed non-competitive inhibitor of TS from murine leukemia (L1210) cells when 5,10-CH2FH4 is varied. This result suggests formation of an inactive complex between TS, 5,10-CH2FH4 and the inhibitor. Thus, binding to only one of the two active sites on the TS homodimer may be sufficient to prevent catalysis fully. Treatment of L1210 cells with ICI D1694 is known to cause intracellular accumulation of the tetraglutamate derivative which is shown here to have a 60-fold higher affinity for TS. The IC50 for inhibition of L1210 cell growth is below the Ki value of ICI D1694 for L1210 TS but above that of the tetraglutamate. The formation of polyglutamates and concentration of drug inside cells, therefore, seem to be responsible for biological activity. PMID- 1596290 TI - The dispositional enantioselectivity of indobufen in man. AB - The plasma pharmacokinetics and urinary elimination of the enantiomers of indobufen (2-[p-(1-oxo-2-isoindolinyl)-phenyl]butyric acid), a novel platelet aggregation inhibitor, have been studied in male healthy volunteers given either the racemic compound or the S-enantiomer (200 mg racemate, 100 mg S-enantiomer). Enantiospecific analysis of indobufen in plasma and urine was achieved by HPLC of its L-leucinamide diastereoisomers. After administration of the racemate, the pharmacokinetic behaviour of the R- and S-enantiomers differed, the plasma levels of the S form declining more rapidly [half-lives = 6.2 hr (S), 8.7 hr (R)]. No substantial differences were observed in terms of plasma level profile of S indobufen when administered alone and in the racemic mixture. A statistically significant difference between the two enantiomers after administration of the racemate was found in the area under the curve (AUC), peak plasma levels (Cmax) and elimination half-life (t1/2 beta) whereas no statistically significant difference was detected in the time of peak (tmax). When the pharmacokinetic parameters Cmax, AUC, t1/2 beta and tmax of S-indobufen administered alone or as racemate were compared, there were no statistically significant differences between treatments as well as between periods and sequences. The urinary excretion of total S-indobufen (free + glucuronide) and of total R-indobufen after administration of the racemate was essentially the same. No difference was observed either in the urinary excretion of total S-indobufen after administration of the racemate or of the S-enantiomer. PMID- 1596291 TI - Intestinal active absorption of sugar-conjugated compounds by glucose transport system: implication of improvement of poorly absorbable drugs. AB - The intestinal absorption of glucose- and galactose-conjugated compounds was studied in the everted sac of the rat small intestine. The absorption clearance of p-nitrophenyl beta-D-glucopyranoside (p-NPglc) at 250 microM in the mucosal side (4.45 +/- 0.34 microL/min/cm, mean +/- SE, N = 4), calculated by dividing the absorption rate by the drug concentration, was significantly decreased (0.476 +/- 0.036 microL/min/cm) in the presence of 1 mM phloridzin, an inhibitor of glucose transport, and in the absence of Na+, a cosubstrate of the glucose transport carrier (0.424 +/- 0.018 microL/min/cm). The absorption clearance of p NPglc was decreased as its concentration increased. In the same experiment, the absorption clearance of p-nitrophenyl beta-D-galactopyranoside (1.99 +/- 0.23 microL/min/cm) was also significantly decreased in the presence of phloridzin and in the absence of Na+. However, the absorption clearance of p-nitrophenyl beta-D mannopyranoside (0.811 +/- 0.013 microL/min/cm) was low and not significantly decreased in the presence of phloridzin (P greater than 0.1). Furthermore, the absorption clearance of beta-naphthyl beta-D-glucopyranoside and beta-naphthyl beta-D-galactopyranoside was also significantly decreased in the presence of phloridzin (P less than 0.001). These results indicated that the glucose and galactose moieties provided these compounds with a new route by way of the glucose transport carrier for intestinal absorption. PMID- 1596292 TI - Oral contraceptives, fibrinogen and cardiovascular risk. AB - Today there can be little doubt about the fact that fibrinogen is a major, independent cardiovascular risk factor. Therefore one should consider circumstances that might lead to an increment of plasma fibrinogen levels. Oral contraceptives (OCs) have been reported to be associated with high fibrinogen. The present review details the information on this potentially important side effect. Cross sectional studies report both increased fibrinogen in OC users as well as no such change. Longitudinal studies yield a much clearer picture. They demonstrate that OCs lead to a significant rise in fibrinogen within 1-3 months of medication. The effect seems to be strongest in OCs with a high oestrogen concentration. Upon discontinuation, fibrinogen returns to normal, usually within about 3 months. These findings suggest that OC use might contribute to the cardiovascular risk partly by elevating fibrinogen levels. PMID- 1596293 TI - Hypolipidemic drugs reduce lipoprotein susceptibility to undergo lipid peroxidation: in vitro and ex vivo studies. AB - Oxidized LDL, which has been discovered in vivo in areas of proximity to the atherosclerotic lesion, has been shown to enhance macrophage cholesterol accumulation. We studied the anti-oxidant potential of pravastatin, bezafibrate and cholestyramine in 18 patients with hypercholesterolemia. In addition, we examined the electrophoretic mobility and the uptake of LDL by macrophages before and after drug therapy. Pravastatin lowered plasma levels of LDL cholesterol by 57%, cholestyramine by 27% and bezafibrate by 25%. Pravastatin and bezafibrate also altered the composition of LDL as evidenced by the reduction of its cholesterol/apo B100 ratio. Pravastatin and bezafibrate reduced plasma triglyceride levels by 45% and 25%, respectively, whereas cholestyramine raised plasma triglyceride concentrations by 28%. LDL propensity for in vitro oxidation was analyzed following lipoprotein incubation with 10 microM copper ions and determination of LDL malondialdehyde (MDA), peroxides (PD) and conjugated dienes (CD) content. All drugs inhibited the susceptibility to in vitro oxidation of LDL isolated after drug therapy in comparison to LDL isolated before commencing drug therapy. Pravastatin reduced MDA content by 22%, PD by 18% and CD by 20%. Cholestyramine reduced LDL content of MDA by 41%, PD by 25% and CD by 63%. Bezafibrate reduced MDA by 41%, PD by 38% and CD by 45%. LDL vitamin E content was reduced after treatment with bezafibrate, pravastatin and cholestyramine by 49%, 36% and 8%, respectively. The electrophoretic mobility of LDL after all drug therapies was reduced in comparison to LDL obtained before therapy. Macrophage uptake of LDL assessed by either the cellular cholesterol esterification rate or by lipoprotein degradation was not affected by drug therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596294 TI - Effects of hypophysectomy on vascular insulin-like growth factor-I gene expression after balloon denudation in rats. AB - Insulin-like growth factor-I (IGF-I) is a widely distributed mediator of the growth promoting effects of growth hormone (GH). We sought to determine whether the relationship between GH and IGF-I extends to the vascular system, where IGF-I is proposed to participate in the process of neointimal proliferation after balloon denudation. We show that in hypophysectomized rats basal aortic IGF-I mRNA is one-tenth that of normal rats and is increased after balloon denudation. The induction peaks at 7 days after balloon denudation at about 10-fold control levels, similar to normal rats. Treatment with GH restores basal IGF-I mRNA content to approximately half that of normal rats, without further increase in the relative magnitude of induction after balloon denudation. This local induction of IGF-I gene expression in the vessel wall following injury might explain why neointimal proliferation is not inhibited more profoundly after hypophysectomy. PMID- 1596295 TI - Effects of chronic aortic coarctation on atherosclerosis and arterial lipid accumulation in the Watanabe hereditary hyperlipidemic (WHHL) rabbit. AB - The effects of high blood pressure on atherosclerosis were examined in the Watanabe heritable hyperlipidemic (WHHL) rabbit. For this purpose, the subdiaphragmatic aorta of rabbits was partially ligated (coarctation) to increase blood pressure. Atherosclerosis was assessed 4 months later by morphometric analyses and quantitation of arterial lipids. Results were compared to control WHHL rabbits with matched plasma triglycerides and cholesterol levels. A marked increase in atherosclerotic lesions was observed in the thoracic aorta of the hypertensive rabbits without qualitative changes in its morphometric features. The cross sectional area of the atherosclerotic plaques of the ascending and descending aorta in the hypertensive rabbits was two- and six-times larger than in normotensive rabbits, respectively. Lesions represented 12.0% +/- 3.5% of the total medial cross sectional area of the descending aorta of normotensive rabbits, versus 45.0% +/- 5.7% in hypertensive rabbits. No lesions were observed downstream of the coarctation in hypertensive rabbits, nor in the normotensive rabbits. Accumulation of cholesterol and choline-containing phospholipids in the descending aorta of hypertensive rabbits was increased 3.2- and 1.5-fold, respectively, when compared to normotensive rabbits. Hypertension did not change the unesterified cholesterol/total cholesterol and sphingomyelin/lecithin + lysolecithin molar ratios. In conclusion, chronic coarctation enhances the atherosclerotic response in WHHL rabbits in the high blood pressure compartment, and reduces the variability of this response. PMID- 1596297 TI - Heparin and neointimal thickening in an organ culture of human saphenous vein. PMID- 1596296 TI - Functional responses of hindlimb circulation in aged normal and WHHL rabbits. AB - Normal New Zealand and Watanabe heritable hyperlipidemic (WHHL) rabbits, about 24 months old, were prepared, under anaesthesia, for recording blood pressure and hindlimb blood flow. Changes in hindlimb vascular resistance were measured after local intra-arterial bolus injection of increasing doses of acetylcholine, bradykinin, serotonin, sodium nitroprusside and phenylephrine. In WHHL rabbits basal hindlimb blood flow was reduced (from 22.6 +/- 3.0 to 12.5 +/- 1.8 ml/min; P less than 0.05) and hindlimb vascular resistance was increased (from 4.6 +/- 0.5 to 8.2 +/- 1.5 mmHg/ml per min; P less than 0.05). No difference was observed in response to acetylcholine, serotonin, sodium nitroprusside and phenylephrine. The only marked alteration found in WHHL rabbits was a clear deficit to bradykinin stimulation. Morphological analysis, using scanning and transmission electron microscopy, indicated a clear damage of the femoral artery, like the presence of atherosclerotic plaques, and an abnormal distribution of patent microvessels in the WHHL muscles of the leg. Peripheral circulation in WHHL rabbits shows some peculiar features, like increased basal vascular resistance and a selective impairment of bradykinin responses. Together with these abnormalities, it seems that responses to various other dilating or contracting agents are normal, suggesting that in this interesting animal model of atherosclerosis the alterations are more specific than in other models. PMID- 1596298 TI - Immunoglobulins, complement components and lymphocyte subsets are related to plasma lipoproteins in healthy children. PMID- 1596299 TI - Streptavidin binds to a 130-kDa protein from solubilized human skin fibroblast and Hep G 2 cell membranes. PMID- 1596300 TI - Response to treatment with simvastatin in a compound FH heterozygote. PMID- 1596301 TI - Elastase-type enzymes and their relation to blood lipids in atherosclerotic patients. AB - Serum elastase-type activity, elastase inhibitory capacity and their relation to lipids were examined in 140 male patients with ischemic vascular disease (coronary, cerebral, peripheral) and in 60 control subjects. In a further 24 patients with acute myocardial infarction elastase activity, inhibitory capacity and lipids during the course of the illness have also been investigated. Serum elastase-type activity was found to be significantly lower and inhibitory capacity significantly higher in the groups of patients than in the controls. HDL and HDL2-cholesterol as well as apo A concentration showed significant negative correlation with elastase inhibitory capacity both in atherosclerotic and in control subjects. During the course of myocardial infarction a significant elevation of serum elastase-type activity could be observed at the end of the first week; serum triglyceride levels increased, HDL- and HDL2-concentrations decreased significantly in the first 3 weeks, than gradually approached the initial values. In the patients with an elevation of serum elastase-like activity by more than 30% in the first week, there was a significantly higher elevation of serum GOT and LDH1 and a greater occurrence of transmural (Q) infarction than in those with a smaller variation of elastase-like activity. PMID- 1596303 TI - Increased serum apolipoprotein(a) in patients with chronic renal failure treated with continuous ambulatory peritoneal dialysis. AB - Patients with end-stage renal failure (ESRF) on renal replacement therapy are at significantly increased risk of cardiovascular disease. To determine whether altered concentrations of apolipoprotein(a) (apo(a)), the plasminogen-like protein moiety of the atherogenic particle lipoprotein(a), contributed to this increased risk, apo(a) concentrations were measured in 48 non-diabetic patients with ESRF treated by continuous ambulatory peritoneal dialysis (CAPD) therapy and compared with 65 controls. Apo(a) concentration was increased in CAPD patients compared to controls (geometric mean 419 units/l versus 137 units/l; ratio of means 3.06 (95% CI 1.95-4.80). We conclude that CAPD patients have increased apo(a) concentrations which may contribute to their increased risk of cardiovascular disease. PMID- 1596302 TI - Formation of intimal cushions in the ductus arteriosus as a model for vascular intimal thickening. An immunohistochemical study of changes in extracellular matrix components. AB - There is a great resemblance in the sequence of events that take place in the pathological development of intimal thickening, so called arteriosclerosis and the formation of intimal cushions in both the normal ductus arteriosus (DA) and the persistent ductus arteriosus (PDA). The human DA was used as a model to study the changes in the extracellular matrix during this process with immunohistochemistry. The formation of intimal cushions was studied in 4 normal fetal DA, 4 normal mature DA and 3 persistent DA. The process of intimal thickening in the fetus starts in the second trimester of pregnancy with an accumulation of glycosaminoglycans in the subendothelial region (SER), accompanied by separation of endothelial cells from the internal elastic lamina and followed by migration of smooth muscle cells into the subendothelial region. This phenomenon was also observed in the mature DA in the neonate, indicating that cushion formation is a continuous process. Intimal cushions had also developed in the persistent DA, although they were morphologically different from the cushions found in the normal mature DA. It was remarkable that two elastic lamellae could be distinguished: one at the original site on the borderline of intimal cushion and media and the other in a subendothelial position. The endothelial cells were firmly attached to this subendothelial lamina, which was wrapped in the basal lamina components laminin and type IV collagen. The main morphological difference between the normal mature DA and the persistent DA is the close relation between endothelial cells and the subendothelial elastic lamina, suggesting an altered elastin metabolism in the PDA. PGI2 synthase was increased in the wall of both the normal and persistent DA as compared with the aorta. It may be related to a role of PGI2 in the formation of intimal cushions. PMID- 1596304 TI - Is fat restriction needed with HMGCoA reductase inhibitor treatment? AB - Fourteen women and five men participated in a 20-week controlled, cross-over trial of the interaction of simvastatin, an HMGCoA reductase inhibitor, with high and low fat diets. Simvastatin was found to be just as effective at lowering LDL cholesterol whether the subjects were on a 22% fat diet or a 38% fat diet (25% and 29% falls, respectively). Nevertheless, the lowest cholesterol levels were achieved by combining simvastatin with a low fat diet, the latter adding a further 5% reduction in plasma cholesterol. Simvastatin plus a low or high fat diet increased HDL cholesterol by 10.0% and 2.9% respectively (P = 0.003 overall) and reduced triglyceride concentration by 15.9% and 19% respectively (P less than 0.001). Significant diet-drug interactions were seen in LDL and HDL3 cholesterol. Simvastatin blunted the effect of dietary fat change so that the difference in LDL cholesterol, which was 0.71 mmol/l between high and low fat in the absence of simvastatin, was only 0.22 mmol/l with simvastatin. On a high fat diet, simvastatin produced almost no rise in HDL3 cholesterol whereas on a low fat diet HDL3 cholesterol was increased by 8.8% with simvastatin. The cholesterol content of VLDL and LDL were significantly reduced by simvastatin. The effects of diet and drug on apoproteins A-I and B resembles those on HDL and LDL cholesterol. The findings show interactions between simvastatin and dietary fat which have a bearing on the treatment of hypercholesterolemia. PMID- 1596305 TI - Essential phospholipids modify immunological functions and reduce experimental atherosclerosis in rabbits. AB - Atherosclerosis was induced in male mongrel rabbits with a high-fat diet and the influence of essential phospholipids (EPL) on plaque formation, parameters of lipid metabolism and immunological functions was studied. When EPL were added to the high-fat diet there was a significant reduction in the area of atherosclerotic involvement of the aorta. The serum concentration of lipids decreased, often to normal values, and cholesterol esterified with polyunsaturated fatty acids appeared. Normalization of the malonyldialdehyde level in plasma was accompanied by a decrease in the concentration of ascorbate free radicals in blood and liver. The high-fat diet caused a depression of both non-specific and specific immune functions studied. With EPL in the diet the tests showed near normal or normal values. It is inferred from these results that a normal state of the immune system is important for preventing the progress of atherosclerotic changes. This is discussed with reference to the role of some immune cells in the metabolism of lipids and to participation of essential phospholipids in plasma membrane functions. PMID- 1596306 TI - Microalbuminuria and associated cardiovascular risk factors in the community. AB - The prevalence of microalbuminuria and relationship to cardiovascular risk factors was examined in a cross-sectional community survey of cardiovascular risk factors. Microalbuminuria (when classified as albumin concentration greater than 20 micrograms/ml) was present in 6.3% of subjects but in conjunction with an albumin/creatinine ratio greater than 3.5 in only 2.2%. Diastolic blood pressure, prevalence of abnormal electrocardiographs, and to a lesser extent systolic blood pressure and fibrinogen concentration, were greater in those with albuminuria concentrations greater than 20 micrograms/ml. The strongest positive univariate correlates of albumin/creatinine ratios in those with detectable albuminuria were age, fibrinogen, blood pressure, total- and low density lipoprotein-(LDL) cholesterol, apo B and alcohol intake, whereas fasting insulin and insulin resistance were inversely correlated. Multiple regression analysis revealed that age, gender, systolic blood pressure and insulin resistance independently accounted for 37% of the variability in albumin/creatinine ratios. When those 10 subjects with microalbuminuria and albumin/creatinine ratios greater than 3.5 were matched with 20 with normoalbuminuria for age, gender and body mass index, the microalbuminuric subjects had significantly lower LDL cholesterol/apo B ratios and a tendency to lower high density lipoprotein (HDL) cholesterol and HDL cholesterol/apo A1 ratios. Microalbuminuria is uncommon in the general population, and is related to ageing, blood pressure and other vascular risk factors. It may reflect the presence of established cardiovascular disease. PMID- 1596307 TI - The effect of bezafibrate on very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) composition in type 1 diabetes associated with hypercholesterolaemia or combined hyperlipidaemia. AB - Lipoprotein composition was examined in type 1 diabetic subjects with hypercholesterolaemia +/- hypertriglyceridaemia during a 3-month double-blind placebo controlled assessment of bezafibrate therapy. The predominant effect was on lipoprotein lipid content. In those with hypercholesterolaemia alone, bezafibrate significantly reduced the cholesterol (particularly esterified cholesterol) and triglyceride content of large very low density lipoprotein (VLDL) (Svedberg flotation units (Sf) 60-400) in comparison to the placebo group (P less than 0.05), and a trend towards a reduction in free and esterified cholesterol within the intermediate density lipoprotein fraction (IDL) (Sf 12-20) was noted. Low density lipoprotein (LDL) composition was unaltered and in general phospholipid and protein concentrations and cholesteryl ester/protein ratios within the lipoprotein fractions were unaffected. Large VLDL cholesterol and triglyceride concentrations in those with combined hyperlipidaemia were significantly decreased following bezafibrate therapy, both in comparison to placebo-treated subjects and to baseline concentrations (P less than 0.05). An additional significant reduction in small VLDL (Sf 20-60) free cholesterol was recorded (P less than 0.05). Average reductions of large and small VLDL protein of 50-56% were not significant because of wide variation in responses. Bezafibrate had no effect on the abnormal composition of IDL and LDL, characteristic of Type 1 diabetes, regardless of whether or not hypertriglyceridaemia was associated with hypercholesterolaemia. Its major action was to lower VLDL lipid concentrations, but it may also reduce the lipid content of intermediate density lipoprotein in Type 1 diabetes. PMID- 1596308 TI - Ability of the LDL receptor from several animal species to recognize the human apo B binding domain: studies with LDL from familial defective apo B-100. AB - To verify whether the LDL receptors from different animal species recognize the binding domain of human apo B-100 we studied the interaction of LDL from control and familial binding defective apo B-100 (FDB) with cultured cells. Human, monkey, bovine, guinea pig and rabbit LDL receptors distinguish between normal and binding defective LDL with a displacement ratio (defective/normal) of 3.3, 2.6, 3.4, 3.1 and 2.0, respectively. Guinea pig and rabbit receptors, however, showed affinities 2-3-fold lower than the human receptor. Hamster, rat and mouse cells failed to differentiate between normal and FDB LDL with a ratio of 1.2, 0.8, and 1.4; the apparent affinities were 4-8 times lower than that of the human receptor. The data from the latter species suggest that the LDL receptor recognizes an area of human apo B different from the human receptor binding domain. The ability of antibody Mb47 to inhibit the binding of human LDL to human, rabbit and guinea pig but not to mouse cells further stresses this concept. Moreover, in 17 alpha-ethinyl estradiol-treated rats the rate of disappearance from plasma of FDB and control 125I-labelled LDL was identical, thus confirming the in vitro observations. These data suggest that the binding domain of the LDL receptor is functionally conserved in man, monkey, cow, rabbit and guinea pig, but is quite distinct in rat, mouse and hamster. PMID- 1596309 TI - Spectroscopic analysis of the unfolding of transition metal-ion complexes of human lactoferrin and transferrin. AB - 1. Human lactoferrin and transferrin are capable of binding several transition metal ions [Fe(III), Cu(II), Mn(III), Co(III)] into specific binding sites in the presence of bicarbonate. 2. Increased conformational stability and increased resistance to protein unfolding is observed for these metal-ion complexes compared to the apoprotein form of these proteins. 3. Mn(III)-lactoferrin and transferrin complexes exhibit steeper denaturation transitions than the Co(III) complexes of these proteins suggesting greater cooperativity in the unfolding process. 4. The incorporation of Fe(III) into the specific metal binding sites offers the greatest resistance to thermal unfolding when compared to the other transition metal ions studied. 5. Non-coincidence of unfolding transitions is observed, with fluorescence transition midpoints being lower than those determined by absorbance measurements. 6. Fully denatured proteins in the presence of urea and alkyl ureas exhibit fluorescence wavelength maxima at 355 356 nm indicative of tryptophan exposure upon protein unfolding. PMID- 1596310 TI - Probing angiotensin receptors. PMID- 1596311 TI - [Pererga and paralipomena]. PMID- 1596312 TI - [Artificial intelligence methods for support of medial patient education before surgical interventions in the region of the neck-nose-ear]. AB - As a rule, curative operations require the patient's consent. Determined by the expansion of surgical possibilities, the kind and frequency of specific complications are subjected to constant changes. The physician is encouraged to explain therapeutic methods as well as the probability of complications within the patient's grasp. It has been investigated to what extent methods of artificial intelligence (AI) are suited for assisting the physician in this task. For this purpose, a comprehensive list of surgical complications as reported in research literature has been compiled. The list has been transferred into a hierarchical structure which can be depicted as a rule tree classified according to topographic aspects. In each otolaryngological operation, the reported complications can be classed with these rules. By employing an expert system (Fig. 1), the physician is capable of compiling an individualized document of agreement (Fig. 2) which serves as a basis for the explanatory talk with the patient. PMID- 1596313 TI - [Reconstruction of defects of the anterior wall of the frontal sinus using autologous bone transplantation obtained by calvarian split graft]. AB - We present the technique to gain free calvarian split bone grafts for reconstruction of the anterior wall of the frontal sinus. The indication for surgery, the surgical technique and the results in 12 patients are discussed. PMID- 1596314 TI - [Detection of human papillomaviruses (HPV) in laryngeal papilloma. An in situ hybridization study]. AB - Together 35 papillomas of the larynx (8 juveniles, 27 adults) were studied for the presence of HPV-DNA by means of nucleic acid hybridization. The hybridization procedure was carried out "in situ" with biotinylated probes of HPV 6/11 and 16/18 under stringent conditions. The results are shown in Table 1. In all juvenile papillomas we detected HPV 6/11, but we did not find positive signals after hybridization with HPV 16/18, 25 (92.6%) of the examinated adult papillomas were HPV 6/11 positive. The detection procedure of HPV 16/18 was positive twice (11.8%). The results of our studies support the hypothesis of HPV 6/11 in development of larynxpapillomas. PMID- 1596315 TI - ["Nucleolar organizer regions" as a factor for the prognosis of laryngeal cancer?]. AB - The prognostic significance of silver-binding nucleolar organizer regions (AgNORs) was assessed in tissue sections of primary tumours taken from 30 patients with squamous cell carcinomas of the larynx. By means of semiautomated image analysis the AgNORs of 100 tumour cell nuclei were measured. Their number as well as their area were evaluated together with morphometrical features (obtained by automated image analysis) and histopathological and clinical data. Considering the mean number of AgNORs the multivariate discriminant analysis revealed significant differences between carcinomas of patients, who were alive of at least 3 years without local or distant recurrence and those, who had died of laryngeal cancer (p less than 0.03%). There was, however, no correlation between the AgNOR number and the DNA features. But, on the other hand, the DNA features, e.g. the 5c exceeding rate according to Bocking and the DNA index according to Atkin were found to be correlated with the tumour size (p less than 0.08%). These preliminary results indicate that the AgNOR number as well as the DNA features could be independent prognostic parameter in laryngeal squamous cell carcinoma, complementary to the staging categories. PMID- 1596316 TI - [A case of leishmaniasis with isolated disease of the larynx]. AB - We report about a 63-year-old man with a mucocutaneous leishmaniasis. Besides the rareness of the disease in Middle Europe the exceptional location in the larynx is remarkable. PMID- 1596317 TI - [Effect of preventive glucocorticoid administration on edema formation and inflammation susceptibility after microlaryngoscopy]. AB - 51 patients, who underwent direct laryngoscopy under general anesthesia, received either 250 mg Methyprednisolone or 10 ml NaCl 0.9% intraveneously in a prospective, double blind study. 4-5 hours after microlaryngoscopy they were examined in regard to edema and size of redness of certain anatomical structures of the larynx and hypopharynx. Findings were compared to the results which had been found on the eve of the operation. There was no statistically significant difference between the two groups. However, in the NaCl-Group there was a direct correlation between the edema formation and inflammatory reaction on one hand and the duration of surgery on the other hand. Routine prescription of Cortisone before mikrolaryngoscopy is not necessary, but is recommended, when the operation is expected to take a long time, around more than 30 min. PMID- 1596318 TI - [Visagnost--a strip test for in vitro allergy diagnosis in comparison with Magic Lite and Cap-FEIA: I. Total IgE determination]. AB - The diagnosis of allergic airway diseases, especially allergic rhinitis, is based on medical history, clinical examination and further tests. Since the detection of IgE, total IgE in serum has become a major tool in the diagnosis of immediate allergy. Although in-vivo-tests like skin prick test are performed in almost every allergologist's practice, the capability of determining IgE was restricted to special laboratories. As shown for semiquantitative glucose dipsticks, a rapid and easy method has advantages for both patient and doctor. A recently developed dipstick test (Visagnost, in U.S. Quidel allergy screen) for allergy screening now enables every practitioner to determine total IgE levels within less than one hour. For the evaluation of the diagnostic value of this dipstick test, we compared the total IgE levels in the sera of 56 patients with two modern methods (Magic Lite, Ciba-Corning, and Cap-FEIA, Pharmacia). Visagnost is an enzyme immuno-assay with the solid phase on the dipstick. It can be performed in serum, plasma or whole blood, in this study the test was performed in serum. Magic lite is a combined solid-liquid-phase immuno-assay with a final chemiluminescent reaction, the incubation time is about two hours. Cap-FEIA is a solid phase sandwich ELISA with a fluorescent reaction and an incubation time of at least four hours. Patient's sera were shock-frozen in liquid nitrogen and stored at -80 degrees C until examination. Visagnost gave results in four ranges of minor 20 U/ml, 21-50 U/ml, 51-100 U/ml and more than 100 U/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596319 TI - [Experimental studies of ischemia of the cochlea. Part 1: Method]. AB - For the etiology of certain inner ear diseases e.g. sudden hearing loss, an impaired cochlear blood flow is discussed. The model of the ferromagnetic thrombosis is an atraumatic method to produce a selective ischemia of the inner ear. The measurement of the inner ear potentials EP, MP and CAP can help to elucidate which inner ear structures are primarily impaired by local ischemia. During the action of a magnetic field to the right cochlea an intravenous injection of small iron particles leads to a thrombosis of the cochlear veins. EP, MP and CAP were measured in the thrombosed ear and MP and CAP in the undisturbed contralateral ear. The methods of microsurgery on the middle and inner ear, the electrophysiological measurement techniques of the inner ear potentials and the method of producing a ferromagnetic thrombosis are described in detail. PMID- 1596320 TI - [Immunohistochemical identification of cholesteatoma-associated macrophage populations]. AB - Extensive bone resorption occurring in aural cholesteatoma is responsible for the severe complications of this disease. In the area of active bone destruction, typical multinucleated osteoclasts are rarely seen, but a heavy cellular infiltrate is found. In the present study we tried to characterize the immunophenotype and the functional state of the cells infiltrating the stroma and the epithelial layer of aural cholesteatoma, using a panel of monoclonal antibodies directed against cell type specific antigens. The results were compared with normal retroauricular skin. The vast majority of cells infiltrating the stroma was bone marrow derived and consisted of T-cells and macrophages. By means of the activation markers HLA-DR and Interleukin-2 receptor an immunologically activated state of the majority of infiltrating cells in cholesteatomas was shown. The great number of activated macrophages in cholesteatomas seems to be very important in the cholesteatomatous immunological process. Because of their various immunological functions (antigen presentation to T-lymphocytes, participation in ingestion and killing of different invading microorganisms and synthesizing a great number of substances involved in host defence and inflammation) these cells play a central role in human immunological system. Langerhans cells, however, did not appear to be involved in the immune process of cholesteatoma. The characteristics of the infiltrating cell population with the great number of phagocytic cells suggest an active immune process resulting in autoaggressive bone resorption. PMID- 1596321 TI - [Current aspects of xerophthalmia]. PMID- 1596322 TI - [From a retired nurse's diary]. PMID- 1596323 TI - [The unveiling ceremony of the monument of the Unknown Nurse]. PMID- 1596324 TI - [The nursing process in the care of the mental patient--nursing diagnosis]. AB - The nursing process, in the area of mental health nursing, is a philosophy and a scientific method of holistic and personalized nursing care. It includes four main nursing theories: the holistic theory, the theory of human needs, the general systems theory and the interpersonal theory. Nursing diagnosis, the crucial part of the first stage of the process, is especially discussed with emphasis on the criteria of its appropriateness, the dimensions of the patient to be assessed and the already available psychiatric nursing diagnoses system as a frame of reference. PMID- 1596325 TI - [Ways of avoiding errors in blood pressure taking]. AB - Factors that lead to false measurement and reading of blood pressure (BP) are described and rationalised. Such factors are: inappropriate equipment, false position of the client during measurement of the BP and his relation to the equipment that is used, wrong position of the nurse during the procedure, techniques used as well as other factors which may influence BP. PMID- 1596326 TI - [Experience and feelings of the nurse in the pediatric oncology unit]. AB - The role of the nurse in the Pediatric-Oncology Unit is determinant. The nurse is the connecting ring between the family, who faces the tragedy, and the hospital. Cancer is a disease which threatens the life of the child more than any other illness nowadays. The experiences and the feelings of these specialized nurses depend on the phase of the disease which reflects the overall prognosis of the child. The nurse therefore, is obliged to face all the special problems which are related to the disease itself and to the needs of each child. These problems have to be solved by the nurse at the time of diagnosis, during the remission of the disease, while in relapse, when off therapy as well as close to death. Knowledge, patience, affection, sensitivity are all qualities which make the nurse "sine qua non" in the team which takes care of children with cancer. PMID- 1596327 TI - [Volunteer to Kurdistan]. PMID- 1596328 TI - Fostering integrity in scientific research. AB - The authors trace the history of the now-symbiotic relationship between universities and the scientific enterprise and indicate how remarkable and beneficial this relationship has been. But, at the same time, universities are beset with troubles, many of their own making, and some of their actions are now questioned by the public. The authors indicate the major problem areas and some reasons for them, and then focus on one of the most serious of the universities' troubles, scientific fraud, which was once seen as a marginal problem but is now regarded as a central one by the public, who feel betrayed by the enterprise they are supporting. Just how much fraud actually occurs is hard to know; fraud is difficult to detect and fairly easy to perpetuate. The amount of damage that fraud, both detected and undetected, inflicts is also hard to estimate, but it can be considerable and of various types, one of the worst of which is the erosion of public confidence in the scientific enterprise. The authors urge universities and the scientists they support to be worthy of the public trust and to take seriously their responsibilities for setting, passing on, and enforcing the ethical standards of scientific research. They also propose reforms of some of the underlying conditions that make fraud more likely, so that the scientific enterprise will be strengthened from within, can continue to flourish, and will be worthy of public trust. PMID- 1596329 TI - Modelling the end of mandatory retirement for U.S. medical school faculty. AB - The author used data taken in mid-1989 from the Faculty Roster of the Association of American Medical Colleges to calculate the age distributions of U.S. medical school faculty active at any time from 1978 to 1988 and their age-specific probabilities of separating from their academic positions (e.g., to take another position, to enter the private sector, or to retire). A simple Markov model was constructed to predict the future faculty age distributions, isolating the factors of growth rate, separation probability, and potential delays in retirement. Age projections proved most sensitive to assumptions about future growth rate, less sensitive to the choice of separation probabilities within the range of those observed in the previous decade, and least sensitive to modelled delays in retirement of as much as five years for half the retiring faculty. The same pattern of sensitivity was true of projected turnover. The conclusion is that the end of mandatory retirement alone will have a negligible effect on medical faculty demographics. PMID- 1596330 TI - Tufts' four-year combined M.D.--M.P.H. Program: a training model for population based medicine. PMID- 1596332 TI - A delicate balance. PMID- 1596331 TI - Efficacy of computers in teaching arterial blood gas analysis. PMID- 1596333 TI - Medical schools and America 2000. PMID- 1596334 TI - A role for legislators in teaching community health sciences. PMID- 1596335 TI - Primary care in the curricula of the world's medical schools. PMID- 1596336 TI - Teleconferencing for graduate and continuing medical education. PMID- 1596337 TI - Characteristics of a productive research environment: literature review. AB - What environmental factors stimulate and maintain research productivity? To answer this question, the authors conducted an extensive review of articles and books on research productivity published from the mid-1960s through 1990. This review revealed that a consistent set of 12 characteristics was found in research conducive environments: (1) clear goals that serve a coordinating function, (2) research emphasis, (3) distinctive culture, (4) positive group climate, (5) assertive participative governance, (6) decentralized organization, (7) frequent communication, (8) accessible resources, particularly human, (9) sufficient size, age, and diversity of the research group, (10) appropriate rewards, (11) concentration on recruitment and selection, and (12) leadership with research expertise and skill in both initiating appropriate organizational structure and using participatory management practices. Some of these characteristics are not surprising, although some findings were unexpected, such as that participative governance correlated consistently with research productivity. The differential impact of each of these 12 characteristics is unclear. It is clear, however, that the leader has a disproportionate impact through his or her influence on all of the other characteristics. Yet, an overarching feature of these characteristics is their interdependency. These factors do not operate in research groups as isolated characteristics. Rather, they are like fine threads of a whole fabric: individual, yet when interwoven, providing a strong, supportive, and stimulating backdrop for the researcher. The authors conclude that while at a distance the productive research enterprise looks like a highly robust entity, upon closer inspection it is revealed to be a delicate structure highly dependent on the existence and effective working of numerous individual, organizational, and leadership characteristics. PMID- 1596339 TI - Matriculants' compliance with a required preventive health program. AB - Several organizations have made recommendations about medical students' health. To determine the University of South Florida College of Medicine's concurrence with published guidelines, a prospective analytic study of the 1990 entering class was carried out, using the 1989 class as a control. Enforcement measures not present in 1989 were initiated in 1990. The requirements for the 1990 matriculants were a history and physical examination; tuberculin testing; immunizations to rubella, rubeola, tetanus-diphtheria, and hepatitis B; status of immunity to chickenpox; and proof of health insurance. The results showed that in 1990 expensive requirements had the lowest rates of compliance, and inexpensive ones, the highest rates of compliance. Comparing 1990 with 1989 showed that the enforcement measures significantly improved compliance for expensive requirements, and for requirements that obligated a student to incur a fee because they needed to be updated. The authors conclude that cost is a major deterrent to compliance and that, in order to improve compliance, medical schools must either implement effective enforcement measures or transfer the cost from the student to the institution. PMID- 1596338 TI - Teachers' perceptions of difficulties in teaching ethics in residencies. AB - In 1989 the authors surveyed faculty who were teaching medical ethics in residencies in order to obtain information concerning the goals, formats, topics, and settings of such teaching, as well as the difficulties encountered. Of 163 teachers contacted, 94 (58%) responded and 63 (39%), representing 50 institutions, reported participation in formal ethics teaching programs for residents. The 63 teachers reported using a variety of formats, including ethics rounds, lectures, and incorporating ethics teaching into weekly case-management conferences. Frequently mentioned goals of ethics teaching included improving the residents' skills in reasoning about ethical decisions and improving the residents' understanding of the language and concepts of ethics. Thirty-four of the 63 teachers (54%) taught ethics in hospital settings exclusively and 21 (33%) taught both in hospitals and in outpatient clinics or offices. The teachers identified a number of barriers encountered in carrying out such teaching, most of which can be grouped in six categories: (1) time constraints due to residents' heavy schedules; (2) attitudes of residents that pose obstacles; (3) logistical problems associated with teaching in the clinical setting; (4) time demands placed on teachers; (5) lack of reinforcement for teaching ethics from other faculty; and (6) shortcomings in the background and training of faculty for teaching ethics in the clinical setting. The authors conclude that difficulties are commonly encountered and discuss ways to overcome the principal barriers to effective teaching of ethics in the residency years. PMID- 1596340 TI - Using faculty consensus to develop and implement a medical ethics course. AB - This report describes the development and implementation of a new required course in medical ethics for second-year medical students at the Cornell University Medical College, 1988-89 and 1989-90. The course was specifically designed to teach students who had not yet started their clinical clerkships to think critically and systematically about ethical issues faced by practicing physicians. The goals, structure, and content of the course were developed using an innovative technique, a planning model involving faculty consensus. The faculty members found the planning sessions intellectually challenging and enjoyable, and reported that the sessions added greatly to their teaching of the course. The students' evaluations over the first two years of the course (with 188 of the 201 students--94%--responding) documented the students' satisfaction with the content and the structure of the course, and their belief that the course had achieved its goals. The authors conclude that the faculty's participation in the planning process was crucial to the success of the course. PMID- 1596341 TI - Sources of stress and support for the pregnant resident. AB - In order to clarify the sources of stress and support for pregnant residents, in 1985 the author conducted a retrospective national survey of women obstetricians and gynecologists, surgeons, and psychiatrists. Questionnaires were mailed to 2,000 physicians; 1,197 responded; 373 (31%) had experienced pregnancy during residency. They indicated that major sources of stress included frequency of call, fatigue, long hours, and too little time with spouse or partner. Women medical staff were perceived as supportive, whereas male counterparts were felt to be neutral at best. Most residents had worked up to delivery or to scheduled maternity leave; only 19 had needed medical leave more than a month prior to due date. Maternity leave of less than six weeks was felt to be inadequate, especially for first-time mothers. The author makes recommendations to help minimize problems for pregnant residents and their programs. PMID- 1596342 TI - First-year students' expectations of interacting with minority patients and colleagues. AB - In a 1988-89 pilot study, the authors surveyed the first-year medical students at the University of California, Los Angeles, School of Medicine in order to examine the students' expectations regarding future encounters with minority colleagues and patients, and how these expectations related to the students' own race or ethnicity and their perceived levels of experience with various racial-ethnic groups; 89 of 140 students responded (64%). There were significant positive associations between the students' levels of experience working or interacting socially with blacks or Hispanics (regardless of the students' own race or ethnicity) and their perceived likelihood of practicing with black or Hispanic partners, whereas there were significant negative associations between experience with blacks or Hispanics and the perceived likelihood of living in predominantly white communities. Further, the black and Hispanic students expected to have a higher percentage of their patients from black or Hispanic backgrounds than did other students. The authors suggest that these results underscore the importance of evaluating students' experience as well as race or ethnicity when attempting to increase representation of students with a commitment to serve minority populations. PMID- 1596343 TI - Factors influencing physicians' decisions to remain in emergency medicine. PMID- 1596344 TI - Using locus of control to predict the NBME-I scores of at-risk students. PMID- 1596345 TI - Students' expected practice locations and their tolerance of ambiguity. PMID- 1596346 TI - Impact of a substance abuse curriculum on primary care physicians' attitudes. PMID- 1596347 TI - A written case simulation of osteoarthritis as a predictor of prescribing behavior among family practitioners. PMID- 1596348 TI - Results of the National Resident Matching Program for 1992. PMID- 1596349 TI - Pressure ulcers in adults: prediction and prevention. Quick reference guide for clinicians. Agency for Health Care Policy And Research. AB - These guidelines are presented in a user-friendly format for quick reference in daily practice. The goals are to: 1) identify at-risk individuals needing prevention and the specific factors placing them at risk; 2) maintain and improve tissue tolerance to pressure in order to prevent injury; 3) protect against the adverse effects of external mechanical forces; and 4) reduce the incidence of pressure ulcers through educational programs. An algorithm helps to specify appropriate prevention measures. PMID- 1596350 TI - Preventing pressure ulcers. A patient's guide. Agency for Health Care Policy And Research. AB - These guidelines provide an easy-to-follow format for patients and their families to be active in preventing pressure ulcers. The definition of pressure ulcers, where they form, and risk factors are described. Key steps in prevention of each risk factor and care to be expected for each risk factor are presented along with additional resources. PMID- 1596351 TI - Changing trends in the management of pelvic pressure ulcers: a 12-year review. AB - The purpose of this study was to evaluate the effect of a preferential shift toward increased use of muscle flap coverage for surgically treated Stage IV pelvic pressure ulcers. Patients treated from 1979-1990 were studied since 1979. Muscle flap use increased from 57% to 100% of surgically treated cases. Over this same period the number of operations per ulcer declined from 1.9 to 1.1 and the time to complete healing dropped from 12.8 to 4.8 weeks. While other factors (including advances in supportive care) have also played a role, increasing use and familiarity with muscle flap has been largely responsible for these improvements. PMID- 1596352 TI - A clinical comparison of two pressure-reducing surfaces in the management of pressure ulcers. AB - The purpose of this study was to compare the clinical outcomes of pressure ulcers treated on a low-air loss bed and a foam mattress with loose-fitting top cover. The two-group, non-randomized study design consisted of a convenience sample of 20 subjects: 10 subjects treated on the low-air loss bed and 10 subjects treated on the foam mattress with loose-fitting top cover. Subjects were selected from among patients located in the medical/surgical, critical care, and the skilled nursing units of a metropolitan public teaching hospital. Descriptive data, laboratory data, pressure ulcer transparency drawing, and pressure ulcer photographs were obtained on each subject every seven days from two to four weeks. A one-way analysis of variance indicated that there was no statistically significant difference in the pressure ulcer outcomes of subjects treated on the low-air loss bed (Mediscus) compared to the pressure ulcer outcomes of subjects treated on the foam mattress with loose-fitting top cover (Comfortex). Analysis of covariance further indicated no statistically significant difference in the pressure ulcer outcome of subjects treated on either pressure-relieving surface according to the subjects': a) age, percent ideal body weight, presence of pressure ulcer infection; b) leukocyte count, total lymphocyte count, and albumin level; and c) level of sensory perception, moisture, activity, mobility, nutrition, friction, and shear. Results from this study indicate that the low-air loss bed and foam mattress with loose-fitting top cover provide comparable pressure ulcer outcomes. Implications for nursing and recommendations for further study are included in the text. PMID- 1596354 TI - Collaborative roles lead to success in wound healing. AB - Collaboration among all healthcare disciplines leads to success in planning strategies to prevent, treat, or heal pressure ulcers. Collaboration requires a respect for each discipline's scope of knowledge and uniqueness of functions as well as cooperation and communication in all aspects of patient care. The patient should be considered the quarterback and all the disciplines are merely the players. PMID- 1596353 TI - AHCPR guidelines available. PMID- 1596355 TI - Investigation of the Knoll Assessment Scale in a tertiary care facility. AB - The purpose of this study was to assist in assessing the validity and reliability of adaptation of the Knoll Tool, Assessment of Pressure Ulcer Potential. Data were retrospectively collected from charts of a random sample of patients (n = 62) who were admitted to a tertiary care facility. Total risk scores ranged from 0 to 22 with a mean of 8.7 and a standard deviation of 6.37. The alpha for the total assessment tool was .6352 with a standardized item alpha of .5973. Discriminant analysis predicted group membership at 62.9%. Group membership was most accurately predicted in Group 1 (76.9%). Discriminant analysis using a score of 11 predicted only 46.8% of group membership, although Group 1 predicted 88.5% and Group 4 predicted 85.7%. Low predictions may be related to small sample size. PMID- 1596356 TI - Prevention for the 90s--accountability. PMID- 1596357 TI - 9th Ernst Klenk Lecture. Molecular medicine. PMID- 1596358 TI - Evidence for tyrosine-linked glycosaminoglycan in a bacterial surface protein. AB - The S-layer protein of Acetogenium kivui was subjected to proteolysis with different proteases and several high molecular mass glycosaminoglycan peptides containing glucose, galactosamine and an unidentified sugar-related component were separated by molecular sieve chromatography and reversed-phase HPLC and subjected to N-terminal sequence analysis. By methylation analysis glucose was found to be uniformly 1,6-linked, whereas galactosamine was exclusively 1,4 linked. Hydrazinolysis and subsequent amino-acid analysis as well as two dimensional NMR spectroscopy were used to demonstrate that in these peptides carbohydrate was covalently linked to tyrosine. As all of the four Tyr glycosylation sites were found to be preceded by valine, a new recognition sequence for glycosylation is suggested. PMID- 1596360 TI - Mouse apolipoprotein AI. cDNA-derived primary structure, gene organisation and complete nucleotide sequence. AB - Apolipoprotein AI, the dominant protein component of serum high density lipoprotein, is intimately involved in cholesterol homeostasis. Apo AI activates the lecithin-cholesterol acyltransferase within the HDL particle and functions as ligand for a putative HDL receptor--two properties, which render this apolipoprotein a key mediator in reversed cholesterol transport. A functional analysis of the apo AI gene demands the isolation of the mouse apo AI gene for expression as transgenes in different mutant forms in the mouse. Here we describe the isolation of a full length apo AI-specific mouse liver cDNA clone with the human cDNA (892 bp) and the derived amino-acid sequence coding a polypeptide of 264 amino-acid residues. It showed a 70.7% homology to the rat and 66% to the human apo AI sequence. With this cDNA as probe the mouse apo AI gene was isolated and its organization analysed. Four exons, three of which are coding sequences, are aligned similarly to the human gene. The gene embraces 1825 bp between the transcription start, and the poly(A)+ tail attached 62 bp downstream of the stop codon. The complete nucleotide sequence of the four exons and three introns of the mouse apo AI gene was determined and its homology compared with that of the rat and human gene. Extensive deletions and a strongly reduced homology of the three introns of the two genes are obvious. PMID- 1596359 TI - Of orphons and UHOs. Delimitation of the germline repertoire of human immunoglobulin kappa genes. AB - Two problems in defining the germline repertoire of immunoglobulin kappa genes were investigated. One concerns putative transposed V kappa genes (orphons), the other one weak hybridization signals which may or may not turn out to be V kappa genes (UHOs). It was shown by sequencing that the three V kappa genes Z2, Z3 and Z4 are very closely related to the Z1 and V118 genes and to two other genes which had been localized on chromosomes 1 and 22, i.e. outside the kappa locus on chromosome 2. It is therefore likely that also the Z2-Z4 genes are orphons and not part of the kappa locus. Two UHOs turned out not to contain V kappa-like structures. This together with previous results makes it likely that we have detected all germline V kappa genes with the available hybridization probes. PMID- 1596362 TI - Inhibition of rat liver cyclic AMP-dependent protein kinase by flavonoids. AB - Rat liver cyclic AMP-dependent protein kinase catalytic subunit (cAK), assayed using the synthetic peptide substrate, LRRASLG, is inhibited by a range of plant derived flavonoids. In general, maximal inhibitory effectiveness (IC50 values 1 to 2 microM) requires 2,3-unsaturation and polyhydroxylation involving at least two of the three flavonoid rings. 3-Hydroxyflavone (IC50 value 4 microM), 3,5,7,2',4'-pentahydroxyflavone (IC50 = 10 microM) and 5,7,4'-trihydroxyflavone (IC50 = 7 microM) represent somewhat less active variations from this pattern. Flavonoid O-methylation or O-glycosylation greatly decreases inhibitory effectiveness, as does 2,3-saturation. Various flavonoid-related compounds, notably gossypol (IC50 = 10 microM), also inhibit cAK. Flavonoids and related compounds are in general much better inhibitors of cAK than of avian Ca(2+) calmodulin-dependent myosin light chain kinase or of plant Ca(2+)-dependent protein kinase. Tricetin (IC50 = 1 microM) inhibits cAK in a fashion that is non competitive with respect to both peptide substrate and ATP (Ki value 0.7 microM). When histone III-S is used as a substrate, inhibition of cAK requires much higher flavonoid concentrations. PMID- 1596361 TI - Construction of a plasmid containing the complete coding region of human elongation factor 2. AB - A plasmid pUChEF-2 containing the coding sequence as well as the complete 3' untranslated region (3'UTR) of human EF-2 mRNA was constructed. The plasmid construct was assembled from a cDNA insert of pHGR81 (Rapp et al., (1988) Biol. Chem. Hoppe-Seyler 369, 247-250) comprising the C-terminal portion of the coding region and the 3'UTR, as well as a polymer chain reaction PCR fragment (Rapp et al., (1989) Biol. Chem. Hoppe-Seyler 370, 1071-1075) covering the missing part of the coding region from the amino-terminus. PMID- 1596363 TI - Antigen recognition. PMID- 1596364 TI - The mechanism by which microorganisms avoid complement attack. AB - The complement system provides a critical level of defense against bacterial invasion. Various microorganisms have evolved a variety of mechanisms to allow them to avoid complement lytic and opsonic activity. These range from the formation of factors that destroy activity of complement proteins to the evolution of surface structures that fail to bind, facilitate degradation of, or shed, complement proteins. The range of factors associated with bacterial complement resistance is reviewed here. PMID- 1596365 TI - Innate immunity to a facultative intracellular bacterial pathogen. AB - The murine response to Listeria monocytogenes has long been considered a paradigm of T-cell-mediated immunity. There is, however, substantial evidence that T-cell deficient mice are capable of surviving a L. monocytogenes challenge. Recently, advances have been made in our understanding of the cell biology and pathogenesis of infection. PMID- 1596366 TI - Antibiotic peptides as mediators of innate immunity. AB - Antibiotic peptides are widely distributed in nature. Almost all function as membrane-active agents, disrupting target-cell permeability. Several exhibit a striking selectivity for single-celled microbes over metazoan cells, and as such are amongst the simplest components of the animal's defensive system, which distinguishes environmental microbes from 'self'. PMID- 1596367 TI - Natural killer cells. AB - Although the antigen-specific receptors of T and B lymphocytes have been characterized, the receptors used by natural killer cells to recognize normal cells, tumors, and virus-infected cells have remained elusive. Recently, experimental systems have been developed to identify these structures, and candidate signal-transducing molecules have been proposed. PMID- 1596368 TI - Antigen processing for presentation by MHC class I molecules. AB - The association of peptide fragments with MHC class I molecules is believed to be a requirement for the assembly of the MHC class I molecules in the endoplasmic reticulum, and transportation of the MHC molecules from the endoplasmic reticulum to the cell surface. Recently, investigators have begun to elucidate the mechanisms of fragmentation and transport of peptide fragments within antigen presenting cells, and to define size and structure of naturally processed peptides bound to MHC complexes. PMID- 1596369 TI - Cellular studies on antigen presentation by class II MHC molecules. AB - Particularly prominent during the past year was the analysis of the subcellular compartment in which MHC class II molecules are located. Some investigators also analyzed the site where peptides are generated for MHC class II binding. Studies of invariant chain were particularly important in trying to establish the functional significance of this molecule. PMID- 1596370 TI - Genes in the MHC that may affect antigen processing. AB - Recent evidence indicates that genes required for antigen processing are present in the class II region of the MHC. Two new classes of MHC genes that may encode much of the machinery required in the class I (endogenous) antigen-processing pathway have been discovered. There is evidence that genes required in the class II pathway also reside in this region. PMID- 1596371 TI - Superantigens. AB - Over the past three years superantigens have come to the forefront of immunological research. Studies in a number of laboratories have indicated that superantigens play a central role in shaping the T-cell repertoire in the development of tolerance, autoimmunity and immunodeficiency. This is in addition to their classic role in the pathogenesis of a number of infectious diseases. PMID- 1596374 TI - Innate immunity. PMID- 1596372 TI - Chemistry of peptide interactions with MHC proteins. AB - X-ray crystallographic and peptide-MHC binding studies have begun to clarify the interaction between antigenic peptides and MHC proteins at the molecular level. At the same time, our understanding of the mechanisms of peptide-MHC interactions in physiologic cellular conditions has been significantly expanded by the isolation and characterization of naturally processed antigenic peptides. PMID- 1596373 TI - Complement receptors. AB - Recently, a number of exciting developments have increased our understanding of complement receptors. These advances include determination of the spatial organization of the short consensus repeat unit, analysis of active sites within short consensus repeats, downregulation in vivo of the complement system by a recombinant receptor, elucidation of the structure of mouse receptors and their relationship to human molecules, and the cloning of the human C5a receptor. PMID- 1596375 TI - Granny midwives in Mississippi: career and birthing practices. AB - In this study career and birthing practices of Mississippi granny midwives who held permits and practiced in the early 1980's are reported. Leininger's (1978, 1985) mini ethnonursing method was used as the primary research approach. Although other authors have studied granny midwives in the South using alternate research methods such as Mongeau (1973) in North Carolina using analysis of historical documents and field research; Campbell (1946) in Georgia using field study research; Kroska (1985) in Alabama using mini-ethnography, to date no one has systematically studied granny midwives and their practices in Mississippi. Patterns and themes from verbatim and record analysis data indicate that the Mississippi granny midwives were practitioners who were called by God to practice. The majority had a mother or aunt who had also been a midwife. They used an oligopolistic market approach combined with altruism and care. They practiced family centered maternity care while using three practice modalities of folk, professional and motherwit for enacting their practice. Although their practice was externally regimented, they practiced in an autonomous way as their individual judgment dictated. PMID- 1596376 TI - "Globalization of transcultural nursing: a worldwide imperative". PMID- 1596377 TI - Transcultural care values and nursing practices of Philippine-American nurses. AB - The purpose of this ethnonursing research was to discover, explicate, and analyze the nursing care values and caregiving practices of Philippine nurses working in an American hospital context. The study, which was part of a larger study, was conceptualized within Leininger's theory of culture care. Consistent with the tenets of the theory, a brief overview of Philippine world view, social structure, culture, and ethnohistory was provided. Qualitative analysis of observation-participation and interview data revealed a major care theme of obligation to care. This care theme was supported by three care patterns which were: 1) expressed seriousness and dedication to work, 2) attentiveness to physical care as comfort, and 3) respect and patience as caring modalities. The study also showed that Philippine-American nurses attempted to achieve cultural care congruence by preserving some generic care values and practices, by accommodating to some of the host professional culture's values and practices, and by restructuring or repatterning less serviceable values. Implications for transcultural nursing education, practice, and research were discussed. PMID- 1596378 TI - Cultural diversity has long been the focus of transcultural nursing. PMID- 1596379 TI - Strange myths and inaccurate facts in transcultural nursing. PMID- 1596381 TI - Change, loss, and grief. PMID- 1596380 TI - Transcultural nursing and health care issues in urban and rural contexts. AB - The distinction between urban and rural health care has been based largely on population density, with little attention given to contextual meaning of patterns related to the lifeways of the people. When considering sociocultural factors, the differentiation becomes more complex. In this paper some of the transcultural nursing issues and challenges are discussed in relation to cultural context and health care trends in urban and rural settings. Four urban-rural health-related issues with transcultural dimensions are examined. Migration patterns, diversity among rural communities, utilization of services, and change related to intervention strategies are identified as transcultural nursing knowledge and practice in relation to urban and rural contexts. PMID- 1596383 TI - A case report of Twiddler's syndrome in a pediatric patient. AB - Twiddler's syndrome, the migration of a catheter tip out of a vessel by intentional or unintentional self-manipulation, is presented in a case report of a young child with Langerhans' cell histiocytosis. Since this migration is a potentially serious complication of internal venous catheters, an overview compares and contrasts the differences between internal and external central venous catheters. The need to consider Twiddler's syndrome in an assessment of a patient with an internal venous catheter is emphasized. PMID- 1596382 TI - Neuman systems model used as a guide for the nursing care of an 8-year-old child with leukemia. AB - The Neuman Systems Model (NSM) provides a framework for holistic pediatric oncology nursing practice. In this article, an overview of NSM is given. This model is applied to an 8-year-old child with leukemia for the comprehensive assessment, planning, and evaluation of nursing care. A comprehensive list of nursing diagnoses is categorized by primary and secondary prevention. PMID- 1596384 TI - Setting research priorities. PMID- 1596386 TI - Topotecan. PMID- 1596385 TI - The effects of different central venous line dressing changes on bacterial growth in a pediatric oncology population. AB - Central venous lines are now common in children who need a permanent form of intravenous access. These lines frequently become infected. This study compared the effects of different antiseptics (Hibiclens [chlorhexadine 4%; Stuart Pharmaceutical, Wilmington, DE] and Betadine [povidone-iodine, Clini Pad Corp, Guilford, CT]) used to clean the skin as well as the dressings used to cover the exit site (Tegaderm [3-M Medical-Surgical Division, St Paul, MN] and gauze) on microorganism growth on the skin in a pediatric oncology population. Sixty subjects were recruited from the oncology and bone marrow transplant units of Children's Hospital in Boston, MA. The subjects were randomly assigned to one of four dressing groups. These included: 1, Betadine and Tegaderm; 2, Betadine and gauze; 3, Hibiclens and Tegaderm; and 4, Hibiclens and gauze. Dressings were done on a Monday-Wednesday-Friday basis. Quantitative cultures were obtained before the first and after the fifth dressing changes. There were no significant differences in incidence of bacterial growth between dressing groups (F = 1.05, P = .377). Redness (F = 3.01, P = .037) and swelling (F = 2.75, P = .051) were more frequently seen in Betadine groups. Boys were more often infected than girls. (Chi 2 = 4.075, P = .044). PMID- 1596387 TI - Using music therapy as distraction during lumbar punctures. PMID- 1596388 TI - Future life expectations and self-esteem of the adolescent survivor of childhood cancer. AB - The number of adolescent cancer survivors has increased dramatically over the past decade as the result of improved treatment and diagnostic techniques. This population brings with them unique characteristics and concerns. The present study consisted of interviews with 10 adolescent survivors of childhood cancer and their parents. It investigated the adolescent's present self-esteem, the future life expectations held by both the teenagers and parents, and the relationship between the variables. Results indicated that the adolescents felt moderately competent in their lives (measures of self-esteem) and the parents felt more certain than their children that the teenagers would accomplish the tasks deemed appropriate for entry into a healthy adulthood. Pearson correlations showed a strong relationship between parents' future life expectations and adolescents' self-esteem (r = .82; P = .002), but not between parents' and adolescents' future life expectations or between the adolescents' future life expectations and self-esteem. The results are significant in addressing the impact parents can have on their child's self-esteem. PMID- 1596389 TI - Don't sell yourself short. PMID- 1596390 TI - Changing central venous catheter lines: evaluation of a modification to clinical practice. PMID- 1596391 TI - Central venous catheter complications: a nursing perspective. PMID- 1596392 TI - The Food and Drug Administration's Device Experience Network: What is it? How does it work? PMID- 1596393 TI - Measuring symptom distress in adolescents with cancer. PMID- 1596394 TI - Imidazoline receptors. A new regulatory concept in blood pressure control. PMID- 1596395 TI - Imidazole receptors and clonidine-displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion. AB - Clonidine, idazoxan, rilmenidine, and comparable agents bind to imidazol(in)e (IR), as well as alpha 2-adrenergic, receptors. Interaction with IRs mediates the hypotension elicited by these drugs at their site of action in the rostral ventrolateral medulla oblongata (RVL) and probably the neuroprotection in focal ischemic cerebral infarction. Unlike alpha 2-adrenergic receptors, IRs are not coupled to G-proteins. Their native ligand may be clonidine-displacing substance (CDS), a potent, partially purified adrenomedullary secretagogue, distributed regionally in brain and some peripheral organs. IRs and CDS may be important in the genesis, expression, and/or therapy of hypertension and stroke. PMID- 1596396 TI - Adrenergic and nonadrenergic effects of imidazoline and related antihypertensive drugs in the brain and periphery. AB - In radioligand binding studies the alpha 2-adrenoceptor antagonist ligand [3H]yohimbine binds exclusively to adrenergic sites. However, in addition to binding to alpha 2-adrenoceptor sites, two other ligands, [3H]clonidine and [3H]idazoxan, also bind at nonadrenergic imidazoline sites. Many of the compounds with a high affinity for these imidazoline sites are centrally acting antihypertensive drugs and there is some evidence that these sites are involved in blood pressure regulation. With chronic treatment of rabbits with guanabenz, clonidine, and rilmenidine, down regulation of alpha 2 but not imidazoline sites occurred in forebrain and hindbrain with guanabenz treatment, and in hindbrain with clonidine treatment. However, no change in either imidazoline or alpha 2 adrenoceptor binding site number occurred in animals given chronic rilmenidine treatment. This rank order of effect, guanabenz greater than clonidine greater than rilmenidine, is consistent with the alpha 2-adrenoceptor activation by the three drugs in the periphery. In contrast, chronic treatment with guanabenz, clonidine, and rilmenidine had similar effects on blood pressure, heart rate, and responses to intracisternal clonidine. We suggest that stimulation of alpha 2 adrenoceptors cannot account for all the changes in cardiovascular responses observed on chronic treatment and that activation of nonadrenergic imidazoline preferring sites may contribute to the antihypertensive properties of imidazoline and related compounds. PMID- 1596397 TI - [Musical medicine: a new medical specialty?]. PMID- 1596398 TI - [Neuro-Behcet. Clinical study of 9 patients]. AB - The authors evaluated the type of neurological involvement existing in patients with Behcet's syndrome over a 10 year period. Nine patients presenting several bouts with neurological symptomatology were studied with headache being clinically predominant followed in order of frequency by sensitive and/or motor ictal pictures. Suspected localization was both hemispheric and brain stem. No diagnostic test was able to clear up the origin of the lesions in the first stages of the disease, however the authors were able to observe, upon performing visual and/or brain stem evoked potentials and nuclear magnetic resonance at the time of the control, that several asymptomatic patients showed alterations in both tests. Thus, the value of the above mentioned tests must be emphasized in the follow up and control of neuro-Behcet's disease. PMID- 1596399 TI - [Neurocutaneous diseases]. PMID- 1596400 TI - [Arnold-Chiari malformation with multiple paroxysmal manifestations induced by coughing]. AB - We present a 66-year old woman suffering from a chronic disorder characterized by multiple paroxysmal symptoms precipitated by coughing. These included cephalalgia, syncope, binocular photopsia phenomena with blurred vision, and an "electric-like" paroxysmal tingling of the hands. In addition to a central spinal cord cavity and hindbrain herniation, magnetic resonance imaging showed multiple skeletal anomalies and the craniospinal junction which included a narrow clivo axial angle, basilar impression of the skull and a tight foramen magnum. Resonance magnetic imaging showed a high-signal intensity lesion on T2-weighted images at the posterior medullo-spinal junction suggesting focal demyelination. We propose that paroxysmal symptoms induced by coughing in patients bearing hindbrain ectopia and skeletal anomalies at the foramen magnum region may involve different pathogenetic mechanisms, including ectopic axonal activity and ephaptic transmission at the sensory pathways. This caused a Lhermitte-like phenomenon precipitated by coughing, rather than by forward flexion of the neck. However, increased pressure at the posterior fossa presumably underlies all these phenomena, and may therefore be potentially relieved by suboccipital decompressive craniotomy. PMID- 1596401 TI - [Acute meningoencephalitis caused by Coxiella burnetii with periodic EEG complexes]. AB - Q fever is a zoonosis found worldwide and is produced by Coxiella burnetii. It may be acute or chronic with neurological manifestations being infrequent. Several cases of acute encephalitis or meningoencephalitis have been described, generally with an evolution towards cure regardless of the use of selective antibiotic treatment. Recently the authors had the opportunity to study a 33 year old male presenting acute meningoencephalitis in which the clinical manifestations, CSF findings (increase in cellularity with lymphocytic predominance and excess proteins ) and neurophysiological findings (appearance of periodic bilateral complexes in the EEG) suggested the diagnosis of herpetic meningoencephalitis. Treatment with acyclovir was initiated. However, serologic studies demonstrated, a posteriori, that the germ responsible had been Coxiella burnetii. The patient evolved satisfactorily with no specific treatment and the EEG anomalies disappeared within a few days. The authors insist on the need to include Q Fever in the diagnostic differential of acute meningoencephalitis and emphasize the possibility that germs of a non viral nature may produce periodic EEG complexes in all that similar to those found in herpetic encephalitis. PMID- 1596402 TI - [Cerebral venous thrombosis and hereditary protein C deficiency]. AB - Protein C together with its plasmatic cofactor protein S and antithrombin III probably represent the most important plasmatic inhibitor in coagulation. Protein C deficiency constitutes a high risk factor for venous thrombosis. Cerebral venous thrombosis is a manifestation which is scarcely referred to in protein C deficiency. The case of a 32 year old patient with protein C deficiency is presented. The patient was admitted for an endocraneal hypertension syndrome. CT and MR demonstrated multiple hemorrhagic cerebral infarctions. Arteriography confirmed vertebral venous thrombosis. Only six cases sufficiently documenting cerebral venous thrombosis due to protein C deficiency were found in the literature. In most cases coadjuvant factors exist predisposing thromboembolic disease. The present clinical case demonstrates the importance of considering protein C deficiency in the diagnosis of cerebral venous thrombosis in young adults. PMID- 1596403 TI - [Treatment of amyotrophic lateral sclerosis with daily intrathecal TRH. A year's experience. Pilot study II]. AB - This study presents the experience of one year of treatment in patients with amyotrophic lateral sclerosis, with intrathecal TRH administered daily by a subcutaneous reservoir connected to the intrathecal lumbar space by a double catheter system as to provide continuous circulation of CSF and to avoid sac formation since this would be a source of infection. Clinical evaluation was carried out with a scale developed by the authors with the main aim of evaluating the loss of vital motor abilities and not as a localized evaluation. Secondary effects due to the implantation of the reservoir in addition to its use are presented although data were not important. Intrathecal administration of TRH was carried out similarly (600 micrograms/day) with secondary effects being the same as those by other routes of administration although of a lesser intensity. The results of the clinical evaluation at the beginning and end of the treatment as well as after patient follow up demonstrated that beneficial effects do not occur equally in all patients but rather are transitory and do not improve the natural evolution of the disease. The authors conclude that, methodologically, this series study does not enter within the frame of an advisable statistical study since the aim is to provide data for a future controlled study. PMID- 1596404 TI - [The etiology of focal cranio-cervical dystonia]. PMID- 1596405 TI - [Reflex epileptic seizures induced by calculation, card or board games and spatio visual abilities]. PMID- 1596406 TI - [Sneddon syndrome and antiphospholipid antibodies]. PMID- 1596407 TI - [Conduction aphasia]. PMID- 1596408 TI - [History of pharmacology. Trends in our time]. PMID- 1596409 TI - [A court case from 1825. Women in confinement and midwives in prisoner's dock]. PMID- 1596410 TI - [A little reflection--first time a BPD-infant dies with us (bronchopulmonary dysplasia)]. PMID- 1596411 TI - [11,447 cases of stroke]. PMID- 1596412 TI - [Guidance of colleagues--a way to increased professional practice]. PMID- 1596413 TI - [ADP in nursing college. Development of new data information system]. PMID- 1596414 TI - [Testing of steam autoclaves]. PMID- 1596415 TI - [Stroke--training is not a lifelong process. Interview by Siv Barstad]. PMID- 1596416 TI - [Drug mathematics for nurses--results from a study in Ostfold]. PMID- 1596417 TI - [How do we calculate drug dosages?]. PMID- 1596419 TI - [Psychiatric nursing. Constant observation as compulsory treatment]. PMID- 1596418 TI - [Medical consequences of medication errors]. PMID- 1596420 TI - [Stroke--Don't give up!. Interview by Siv Barstad]. PMID- 1596421 TI - [Daily life following prostatectomy. Sexual function]. PMID- 1596423 TI - Intraoperative tissue expansion: a review. AB - Tissue expansion is used to facilitate reconstruction procedures following trauma and cosmetic breast augmentation. This article describes tissue expansion, reviews intraoperative expansion techniques, and discusses the nurse's role in the procedure. PMID- 1596422 TI - Dermatologic aspects of HIV in dermatology nursing. AB - Dermatology nurses are playing an increasing role in the assessment and care of HIV-infected patients. Recognition and proper care of the cutaneous manifestations of HIV disease are vital for improving the patient's health and comfort. PMID- 1596424 TI - Psoriasis ambulatory treatment centers: United States experience. AB - Ambulatory psoriasis treatment centers, with appropriately trained staff, provide comprehensive, safe, and effective treatment options. Ambulatory facilities, equipment, personnel, and specific treatment programs are discussed. PMID- 1596426 TI - New OSHA standards released. PMID- 1596425 TI - The Nurse in Washington Roundtable, September 23, 1991--Washington, DC. PMID- 1596427 TI - Female androgenetic alopecia: a review. AB - This review of androgenetic alopecia (AA) in women provides a summary of hair physiology and biochemistry, a general discussion of AA, and a brief description of other types of hair loss in women. AA associated with signs of virilization is distinguished from AA alone. PMID- 1596428 TI - Personal values and contraceptive choices. AB - This article outlines ethical dilemmas often encountered in contraceptive counseling. Central to these issues is the notion of respect for each client's personal values. Information on values, values clarification, patient rights in contraceptive decision making, and nursing duties in contraceptive counseling is presented. Finally, nursing implications, including tools for values clarification, are discussed. PMID- 1596429 TI - Adolescent use of contraceptives. AB - This chapter describes the relationship between adolescent contraceptive use and pregnancy, factors that influence the relationship, and strategies to improving decision making and contraceptive use. Contraceptive choices, with specific recommendations for the adolescent client, are outlined. The role of the nurse is described, and specific suggestions are given to help in counseling the teen-age client. PMID- 1596430 TI - Contraception for the postpartum woman. AB - The postpartum woman has the full array of contraception options available to her to prevent a subsequent pregnancy. Two factors may influence the choice of the method and the timing of the onset of use (when pregnancy risk increases): the infant feeding mode chosen and the reproductive involution process. The major controversial area regarding contraception postpartum is the use of oral contraceptives if the mother is breastfeeding (ie, if and how do steroids affect the lactation process or infant health). This article reviews the physiologic and hormonal changes that occur after birth, examines the data available in relation to the influence of steroidal contraceptives on lactation, and presents postpartum implications of the use of the spectrum of contraceptive choices. The nurse can provide an important role in counseling postpartum women regarding contraceptive alternatives and supporting families in attaining their childbearing goals. PMID- 1596431 TI - Contraception for midlife women. AB - Women wish to continue to be sexually active long after their desire to bear children. The risks associated with unintended pregnancy easily can be avoided by providing women with information about, and access to, contraceptives that are safe and effective. Because fertility naturally declines with age, different contraceptives may be more suitable for women toward the end of their reproductive years than were appropriate at periods of peak fertility. This article discusses the risks and benefits of various contraceptives for midlife women and the implications of this information on nursing practice. PMID- 1596432 TI - The cervical cap. AB - The Prentif cavity rim (PCR) cervical cap offers American women a barrier method alternative that is safe, effective, and convenient. Despite its many advantages and benefits, disadvantages have been documented. These include limited availability and side effects, such as cap dislodgement, partner discomfort, and bad odor of the cervical cap. However, many women decide the benefits and advantages associated with the PCR cervical cap outweigh the risks and possible side effects, making it an appealing alternative. PMID- 1596433 TI - The birth control pill revisited. AB - The evolution of oral contraceptives is summarized in this chapter. The social context into which the birth control pill was introduced, early and recent formulations of the pill, side effects, and the identification of serious complications of taking the pill are presented. The role of the nurse as a health educator of women and the responsibility of nurses to assist patients to make informed decisions about their reproductive function are emphasized. The outlook for future research and development of alternative forms of contraception is discussed. PMID- 1596434 TI - Contraception outside North America: options and popular choices. AB - Recent data indicate that worldwide contraceptive use has reached about 50%. Effective contraceptive methods are being used by increasing numbers of women; sterilization is the most widely used method in the world. In this chapter, sociocultural influences on contraceptive choice are reviewed for selected developed countries and developing countries in Africa, Latin America, and Asia. Demographers predict that fertility control will remain a world problem for many years to come. PMID- 1596435 TI - Innovations in contraception: the Norplant system. AB - The Norplant (Huhtamaki Oy/Leiras Pharmaceuticals, Turku, Finland) contraceptive system is a safe, highly effective, reversible method of hormonal contraception. The system consists of six flexible match-size implants that are implanted in the inner aspect of the upper arm. This sustained-release system delivers the progestin levonorgestrel at levels sufficient to prevent pregnancy for as long as 5 years. Norplant is a convenient, easy-to-use method. Adequate counseling of potential users and appropriate selection of patient users are important determinants of patient satisfaction with Norplant. PMID- 1596436 TI - Natural family planning. AB - Natural family planning includes the calendar (rhythm), basal body temperature, ovulation (mucus), and sympto-thermal methods. Reliability of such methods often is underestimated, but effectiveness of various methods has been reported. Correct understanding and use of proper techniques, primarily abstinence during fertile periods, is imperative for effectiveness. New methods being studied may heighten awareness of fertile times and shorten required periods of abstinence or use of back-up methods. PMID- 1596438 TI - Integration of clinical genetics into assisted reproductive technologies: implications for nursing practice. AB - Assisted reproductive technologies (ART) have moved from the experimental periphery of clinical treatment to the center of routine practice in the field of reproductive endocrinology. With advances in technology, reduced operative risks, increasing third party reimbursement and increased accessibility to ART programs, a more heterogeneous group of couples is seeking these services. The traditional ART couple has been joined by a growing number of couples who are at risk for or affected by a genetic disorder. These individuals seek alternative methods of conception to minimize the risk of conceiving a child with a significant birth defect. Programs offering donor gamete, donor embryo, gestational carrier, and in the future, preimplantation genetic testing must be prepared for the unique needs of the "traditional" infertile and "nontraditional" fertile couple. PMID- 1596437 TI - The role of the expanded function nurse in fertility preservation. AB - The women's health care nurse practitioner has a unique opportunity to provide care to women in all stages of the reproductive life span. The care and guidance provided can affect general gynecologic health and the patient's ability to conceive. Crucial decisions about contraception and life-style choices have a far reaching impact on reproductive potential. Women must be made aware of the issues surrounding these topics so they can make appropriate choices. The nurse practitioner, in the role of primary care provider, can assist women in this decision making process. PMID- 1596439 TI - Recent advances in the treatment of male infertility. AB - The treatment of male infertility has been advanced by developments in the assays used to assess sperm function, methodologies for sperm preparation and augmentation of motility and potential fertilizing ability, and the various assisted reproductive techniques. These have made it possible for fertilization to be achieved even when apparently severe seminal deficits are encountered and have contributed to our knowledge regarding prefertilization and postfertilization events. PMID- 1596440 TI - The nursing role in assisted reproductive technologies. AB - The role of the nurse in assisted reproductive technologies (ART) has evolved as the needs of couples and infertility programs have changed. This multidimensional nursing role encompasses skill as a manager, educator, counselor, researcher, and professional. Such skills are combined with a specialized knowledge base of reproductive endocrinology and infertility. This chapter describes the various facets of the role, including the interdependence of other team members. PMID- 1596441 TI - Redefining the concepts of success and failure in infertility treatment. AB - Technology has been used with increasing frequency to achieve fertility in couples who have experienced infertility. However, the success rates of many of the technology-assisted methods continue to be low. One major consequence of the low success rates is that infertile persons often view themselves as "failures." The major thesis of this chapter is that nurses can play a key role in helping individuals and couples redefine their concepts of success and failure. As a result, these persons can differentiate "treatment failure" from "personal failure" and reframe their meanings of infertility and their views of themselves. PMID- 1596442 TI - Understanding the ethical issues in infertility nursing practice. AB - Nurses are actively involved in planning and providing nursing care to infertile individuals and couples in a variety of health care settings. Infertility is a health problem with ethical and physical, psychological, and social dimensions. Rather than evaluating the ethical advantages and disadvantages of each reproductive technology, the author suggests that the ethical issues that face nurses in caring for infertile individuals be assessed from the standpoint of possible harm to the individual and family. From this perspective, a lack of accurate information about treatment outcomes appears to be a serious ethical issue and one that nurses can, in part, remedy. PMID- 1596443 TI - Creating brave new families with advanced reproductive technologies. AB - The advanced reproductive technologies such as in vitro fertilization, gamete intrafallopian transfer, and donor gametes have created "brave new families," which can no longer be described by traditional definitions based on genetics and gestation. Understanding the particular stresses and issues that these families face can be particularly helpful to the clinician working with these couples and their children. The potential long-term effects also are explored. PMID- 1596444 TI - Ashworth inquiry: one bad apple? PMID- 1596445 TI - Operation clean-up. Cleaning up the campaign. PMID- 1596446 TI - Operation clean-up. Your hospital horror stories. PMID- 1596447 TI - Midwives' recording of urinary output. AB - The prevalence of urinary incontinence in women has been well documented (1, 2, 3), but several women attending a continence clinic also complained of a feeling of not completely emptying their bladder. It was observed that these complaints tended to come from mothers who had had an epidural anaesthetic during labour, with or without a forceps delivery, and when a Foley catheter had been in situ. It occurred in both primigravidae and multigravidae pregnancies. This pilot study examined the extent of documentation of urinary output, measured by midwives, during labour and in the immediate postpartum period when epidural anaesthesia had been administered. This highly susceptible group of mothers can develop hypotonic detrusor activity, which may go unrecognised unless it has been carefully monitored (4). A sample of convenience, over a two-week period from two maternity units, provided 20 mothers for study. They all had epidural anaesthesia and vaginal deliveries. Two questionnaires with predetermined questions were used to collect the data, one for midwives, the other for the investigator in using patients' records. The results showed that documentation for urinary output during labour was recorded for 60 per cent of the sample, while 20 per cent had urinary output recorded in the postnatal ward. It is suggested that 50 per cent of the mothers could have been discharged home with unrecognised hypotonic detrusor activity. PMID- 1596449 TI - Introducing total quality management. AB - Total quality management is a system that could pay dividends for National Health Service managers and employees but would require a change of culture, from one of crisis response to problems to one preventing them from happening in the first place. This article introduces the concept and describes the preconditions for its successful application. PMID- 1596448 TI - Operation clean-up. Control of infection: points to remember. PMID- 1596450 TI - Research in practice: rhetoric or reality? AB - 'Research' has become a fashionable word in nursing circles, but doubts remain about whether nursing is justified in calling itself a research-based profession. The author examines the rhetoric surrounding the word, before citing examples of how research is affecting nursing practice. More work is needed to ensure the gap is closed between talking about research and using it, but nurses should not lose sight of the ultimate aim of research--to enhance the primary vocation of caring. PMID- 1596451 TI - Focus on Trent--community. A seamless service for community care. AB - In an era of rapid change and development related to community care, Trent Health has been rethinking the region's approach to community nursing services. A task group set up to examine the issues led to the circulation of a consultative document: the responses revealed widespread support for the concept of a joint single service specification as the key to a 'seamless service' within the community. Work continues in Trent to clarify how nurses can contribute to achieving an effective seamless service. PMID- 1596452 TI - Operation clean-up. Safety network. PMID- 1596453 TI - The Clay column. PMID- 1596454 TI - Employment: secrets from the agency. PMID- 1596455 TI - Transplant nursing. The gift of life. PMID- 1596456 TI - Transplant nursing. Transplant nursing at Papworth Hospital. PMID- 1596457 TI - Transplant nursing. Educating for quality care. PMID- 1596458 TI - [Tomography, emission-computed--handling, preparation and execution in children]. PMID- 1596459 TI - [Nutrition of healthy newborns in the hospital birthing centers--recommendations by the Commission for Nutrition of the Swiss Pediatric Society]. PMID- 1596460 TI - [Cutaneous leishmaniasis]. PMID- 1596462 TI - [Poisonous and less poisonous plants--introduction]. PMID- 1596461 TI - ["Perception disorders"--what are they? Report of experiences of a pediatric nurse]. PMID- 1596463 TI - [Legislation for the protection of mothers. The nuclear part of legislation for the protection of working women]. PMID- 1596465 TI - [Campaign against declining births--press report from the St. Elisabeth Hospital in Neuburg on the Danube]. PMID- 1596464 TI - [Walter Keller 1894-1967)]. PMID- 1596466 TI - [European guiding policies on education in the nursing professions]. PMID- 1596467 TI - Conformational properties of streptokinase--differential scanning calorimetric investigations. AB - The two-domain structure of streptokinase (Sk) was demonstrated by scanning calorimetric investigations at neutral pH and low ionic strength. The melting pattern of the protein is composed of two two-state transitions at TtrS1 = 45.9 +/- 0.4 degrees C with delta H1 = 431 +/- 18 kJ/mol, and TtrS2 = 60.1 +/- 1.3 degrees C with delta H2 = 306 +/- 16 kJ/mol. The partial specific heat capacity of native Sk was determined to be Cp = 1.42 +/- 0.17 J/K/g and the denaturational heat capacity change associated with the two transitions, delta Cp1 = 0.21 J/K/g and delta Cp2 = 0.38 J/K/g, respectively. The overall melting pattern of Sk remains almost unchanged at a variety of tested solvent compositions, except at pH 4 (and below) and in the presence of denaturants. The two domains show different susceptibility to urea. It is proposed that the less thermostable domain is located within the N-terminal part (residues 1-230), and the more thermostable one, within the C-terminal region. PMID- 1596468 TI - Alpha-beta-dehydro-amino acid residues in the design of peptide structures. Molecular and crystal structures of two folded dehydro peptides. AB - The molecular and crystal structures of two N alpha-protected tripeptide amides, containing in the central position the alpha-beta-dehydro-amino acid residue delta Phe (Z-configurational isomer), were determined by X-ray diffraction. While Z-Gly-delta Phez-L-Pro-NH2 is characterized in the crystal state by the presence of a type I beta-bend conformation (at the delta Phez-L-Pro sequence), Z-D-Ala delta Phez-Gly-NH2 is folded into two consecutive beta-bends (type II' followed by type I), at the D-Ala-delta Phez and delta Phez-Gly sequences, respectively. In both cases the achiral delta Phez residue adopts a set of phi, psi angles typical of the right-handed helical conformation. The delta Phe residue may be exploited to design aromatic peptides with preferred secondary structures. PMID- 1596469 TI - High resolution 13C-n.m.r. spectroscopy of 'mixed linkage' xylans. AB - Three xylan fractions, obtained by stepwise precipitation with ethanol, were analysed by 75-MHz 13C-n.m.r. spectroscopy. Diad frequencies, determined from the C-2 resonances, show that the (1----3)-linkages are interspersed throughout the chain rather than grouped contiguously. This type of distribution is in agreement with a random coil conformation and with the constancy of the optical rotation in solvents of different ionic strength and chaotropic power. These diad frequencies were compared with the theoretical values calculated for a random distribution from the ratio of (1----4)-:(1----3)-linkages in the 1H-n.m.r. spectra, and from the methylation analysis for one of the fractions. PMID- 1596470 TI - Biodeuteration of poly(beta-hydroxybutyrate). AB - The formation of poly(beta-hydroxybutyrate), PHB, by Rhodobacter sphaeroides and Alcaligenes eutrophus was studied using the following carbon sources and solvents: (1), acetate in H2O; (2), D3-acetate in H2O; (3), acetate in 90 to 92% D2O; and (4), D3-acetate in 90 to 92% D2O. The growth of Rb. sphaeroides cultured under condition (2) showed no apparent deuterium isotope effect, while considerably slowed growth in the presence of D2O was observed under conditions (3) and (4). In all cases, the PHB produced under deuterium enriched conditions was of high molecular weight. Interestingly, comparatively high volumetric formation of partially deuterated PHB was obtained using culture condition (4) for A. eutrophus. Fourier transform infrared spectroscopy (FT-i.r.), pyrolysis gas chromatography mass spectrometry (PGC-m.s.), and nuclear magnetic resonance (n.m.r.) were used to establish the extent and distribution of deuterium in the PHB samples produced. Partially deuterated PHB was obtained in each case, using a deuterium enriched culture. Considerable differences in the extent and distribution of deuterium were found between micro-organisms and culture conditions. PMID- 1596471 TI - Phase transitions and chain dynamics, in the solid state, of a pentapeptide sequence of elastins. AB - Differential scanning calorimetry (d.s.c.) and thermally stimulated current (t.s.c.) have been applied to the study of thermal transitions and dielectric relaxations of a pentapeptide sequence: Gly-Leu-Gly-Gly-Val of elastin. The manifestation of the glass transition has been observed by both techniques. The analysis of the fine structure of t.s.c. spectra reveals the existence of local order in the amorphous phase upon physical ageing. In the 'true' amorphous phase, cooperative motions of sequences of various length are observed. The corresponding activation parameters are characteristic of the 'structure' of the amorphous phase and might be used as reference for further studies. PMID- 1596472 TI - Plasticization of poly(hydroxybutyrate) in vivo. AB - The influence of a variety of treatments on the mobility and crystallinity of poly(hydroxybutyrate) (PHB) in whole cells and native granules has been proved using 13C-n.m.r. spectroscopy and X-ray powder diffraction, and correlated with the known biological effects of these treatments. It was concluded that at least water is responsible for PHB plasticization in vivo, and that only native mobile PHB is susceptible to depolymerases. Another, probably hydrophobic, component appears to be involved either as plasticizer or nucleation inhibitor. Three states of the granule are identified in addition to the native, biologically competent state: freeze-drying of whole cells leads to a partially-immobilized amorphous state which can be restored virtually to native mobility by rehydration; extended centrifugation of native granules in aqueous suspension, or treatment with hydrophobic detergents under certain conditions, leads to a crystalline state that is less susceptible to exogenous depolymerase; and heating to 95 degrees C or refrigeration has no detectable effect on mobility but leads to inactivation of the granule, presumably via damage to superficial membrane or protein. PMID- 1596473 TI - Conformational studies of the duplex d-(CCAAAAATTTCC).d-(GGAAATTTTTGG) containing a (dA)5 tract using two-dimensional 1H-n.m.r. spectroscopy. AB - A variety of two-dimensional nuclear magnetic resonance (n.m.r.) techniques were utilized for structural studies of the dodecadeoxy-nucleotide duplex d (CCAAAAATTTCC).d-(GGAAATTTTTGG). Overall, the duplex was found to adopt a conformation of the B-DNA type. Direct measurement of 1H-1H coupling constants of the deoxyribose rings and comparison of nuclear Overhauser effects (NOEs) involving characteristic intra- and inter-nucleotide proton-proton connectivities indicate that the sugar rings are all in predominantly C2'-endo/S-type conformation. The appearance of NOEs between adenine 2H and sugar l'H resonances indicates a narrowing of the minor groove at the 3' end of the (dA)n tracts. Several lines of evidence indicate that a conformational change in the DNA duplex is introduced by the (dA)5 tract, in support of the junction model for curved DNA. The results are compared with previous structural studies of the evidence for curvature in duplex DNA containing (dA)n tracts. PMID- 1596474 TI - An interpretation of cell separation mechanism on polyamine graft copolymers. AB - Interaction between polyamide microcapsules having different balances of negative and positive charges on their surface, that is, different isoelectric points and copolymers with different numbers of polyamine macromer of a definite chain length grafted on poly(2-hydroxyethyl methacrylate) backbone was studied by measuring the amount adhered of the microcapsules onto the surface of copolymer coated glass beads at different pH values. Maximum microcapsule adhesion was observed for a proper combination of microcapsule and copolymer to suggest that separation of a specified cell population from others on the surface of copolymer coated glass beads can be explained in terms of preferential adhesion through electrostatic interaction of the specified cells with the copolymer. PMID- 1596475 TI - Development of a new dynamic method for quantitative evaluation of in vitro hemocompatibility of biomedical materials. AB - In this study a new dynamic method is introduced allowing the estimation of blood cell adhesion on flat test surfaces by measuring the cell loss in the bulk phase of surface contacting test blood under defined rheological conditions. This was achieved by constructing a novel test chamber permitting the contact of small amounts of blood with a large geometrical test surface. The construction consists of a spiral-shaped flow channel of 0.3 cm width, 0.02 cm height and 78 cm length covered with the biomaterials to be tested from both sides. Laminarity of blood flow in the conduit was confirmed theoretically by the calculation of an equivalent to the Reynolds number for curved systems the so-called Dean number. Furthermore, flow laminarity was proved experimentally finding that the flow rate of blood with different hematocrit values was proportional to the hydrostatic pressure applied. The applicability of the novel 'spiral method' for the estimation of hemocompatibility was demonstrated by evaluation of platelet adhesion onto different polymers in comparison to siliconized and fibrinogen coated glass as reference surfaces. Additionally, it was possible under distinct conditions to determine the adhesion of leucocytes and the detachment of platelet aggregates. Therefore, it was concluded that the spiral method can be used for the assessment of the hemocompatibility of flat biomedical polymers. As main advantages of the new method can be considered the high time efficiency and accuracy without labelling or optical detection of adherent cells. PMID- 1596476 TI - In vitro contraction rate of collagen in sponge-shape matrices. AB - Connective tissue substitute can be made of collagen sponge-shaped matrice which is reconstituted by freeze-drying a collagen dispersion. This procedure is then followed by a crosslinking treatment to decrease the in vivo biodegradation rate. In the present study, collagen dispersions made of collagen fibrils with a D staggered pattern were submitted to the following treatments: (1) cyanamide or glutaraldehyde was introduced during the dispersion step followed by the manufacture of sponges; (2) uncrosslinked sponges were exposed to formaldehyde vapor; or (3) uncrosslinked and crosslinked sponges were severely dehydrated. To characterize the in vitro contraction rate, the surface areas of sponges were sequentially recorded in relation to soaking time. Contraction did not significantly occur when sponges were chemically treated. However, collagen in sponges treated by either severe dehydration or by both cyanamide treatment and severe dehydration contracted. On the other hand, the different treatments of the collagen modified the distribution of the D-staggered pattern within fibrils. After glutaraldehyde treatment, the periodicity of collagen fibrils disappeared and large fibres were observed. These experiments show that the different treatments of the collagen can be useful for designing a contractile as well as a non-contractile biomaterial. PMID- 1596477 TI - Link between the ciliary process and lens equatorial current. AB - Circadian and seasonal rhythmic changes in the intraocular pressure are modulated by the nervous system and expressed in the eye by the release of norepinephrine at adrenergic nerve endings. This study links seasonal changes and the effects of the topical application of norepinephrine with changes in the equatorial current of the lens in frogs. A vibrating probe and microelectrodes were used to study the segment of the K+ electrical loop extending between the internal microelectrode, used for measuring potential difference (PD), and the external vibrating electrode, measuring the equatorial current (J). Changes were noted in the electrophysiological parameters of 270 normal frog lenses (Rana pipiens) at different times of the year. Threefold seasonal variations were observed in the amplitude of equatorial current (J) and the resistance associated with the equatorial current (RJ). J was greatest in the winter and RJ was greatest in late spring. Norepinephrine applied directly to the lens did not affect the equatorial current. Norepinephrine applied topically, increased the equatorial current of the lens. It is concluded that the magnitude of the equatorial current of the lens is mediated in part by the ciliary process epithelium. PMID- 1596478 TI - Intraocular silicone oil effects on rabbit blood-retinal barrier permeability. AB - Both short- (1 week) and longer-term (7 week) studies have been made on a series of silicone oils to determine their effects on blood-retinal barrier permeability. About 25% of the vitreous humor was replaced with the test oil, and fluorophotometric determinations made after intravenous fluorescein at intervals after oil injection. The short-term studies revealed a uniform disturbance of the eye at 24 hours after oil injection that probably represents the physical disturbance of the eye during injection. For most oils the readings on day 4 and day 7 after oil injection revealed no difference between the experimental and the paired control eye. Adatomed 5000 cps oil and a Japanese 1000 cps oil caused more sustained aqueous humor fluorescein values over the first week. Longer-term studies, with two oils shown in prior studies on corneal endothelium to increase permeability and one oil that had no influence on endothelial permeability, revealed no effects on fluorescein penetration into any ocular compartment. It is apparent that the corneal endothelium offers a more sensitive paradigm for examining the toxicity of oils for predictive behavior of long-term exposure of the retina. PMID- 1596479 TI - [Pathology of the placenta. IX. Intrauterine fetal death. Regression. Edema and fibrosis of the villous stroma]. AB - Intra-uterine fetal death along with discontinuation of fetal circulation is followed by intraplacental processes which result in the following pathologico anatomic pattern: Fetal vessels in terminal villi are doomed to collapse, with the major arteries being occluded due to proliferation. This is followed by substantial proliferation of connective tissue in peripheral villi, and by total disappearance of capillaries in terminal villi. Possible remnants of cytotrophoblast are lost from trophoblast epithelium, with the syncytiotrophoblast undergoing proliferation. Multiple syncytial proliferations were recorded from cases in which some time had passed from the event of intra uterine fetal death. Stromal fibrosis is introduced by transient activation of mesenchyma of the terminal villi. Complete regression with totally fibrosed (collagenized) villi, vascular occlusion of stem villi, numerous spots of syncytial proliferation, and increased deposition of intervillous fibrin ist the morphological equivalent of missed abortion. Stromal fibrosis of terminal villi is a consequence of regression after intra-uterine fetal death or may possibly result from impairment of placental circulation of different causative background. Certain forms of fibrosis may possibly develop via stromatic edema (e.g. diabetes mellitus, blood group incompatibility, immunological disorders) together with edema-activated mesenchymal proliferation. Edema of villous stroma may be of diffuse or focal manifestation in the terminal villi and in advanced cases may affect all parts of the placenta. It is usually linked to diseases in which the entire fetoplacental unit is prone to edematization (maternal diabetes mellitus). Severe stromatic edema leads to formation of so-called stromatic ducts in which edema liquid is accumulated but is incapable of flowing out for absence of lymphatic drainage of the placenta. PMID- 1596480 TI - Coronary atherosclerosis and hair elements contents. A correlation study of 102 autopsy subjects using the energy dispersive X-ray fluorescence analysis and applying an atherometric system. AB - An atherometric system (AS) was used to study the coronary atherosclerotic lesions of a consecutive series of 102 autopsies divided into two groups according to the principal cause of death, the myocardial infarction and the low atherosclerosis groups, respectively (MIG 67 cases, LAG 35 cases). The hair elements contents (K, Ca, Zn, Br, Sr, Pb, S, Cl, Cu, and their rates Ca/Sr, Zn/Cu and Ca/K) were determined by energy dispersive X-ray fluorescence (EDXRF) analysis. A PEARSON correlation analysis was done between each element and the following descriptive arterial variables of the AS: fatty streaks (X), fibrous plaques (Y), severe (complicated plus calcified) plaques (Z) and total atherosclerosis (sigma) and the three weighted indices of the AS: obstruction (omega), stenosis (P) and benignity (B). These variables were obtained from the three major epicardial branches of the coronary arteries (right RC, left anterior descending LAD and left circumflex LC). From a total of 189 possible correlations between the 9 elements and their 3 combinations and the 7 variables of the AS in the three coronary arteries, 86 (45.5%) were significant. The fatty streak was the best correlated variable. It correlated with all elements with the only exception of chloride. The fibrous plaque was poorly correlated. The severe plaques and total atherosclerosis correlated mainly with Zn and Pb in the MIG and Sr in the LAG. The weighted indices have the same behaviour. Also some correlations were found between K, Ca, Zn, Br, Sr, Pb, Ca/Sr, Zn/Cu and Ca/K ratios with some of the variables of the AS in each coronary artery. PMID- 1596481 TI - Myoid differentiation in vascular transformation of lymph node sinuses due to venous obstruction. Immunohistochemical and ultrastructural studies. AB - Five cases of vascular transformation of lymph node sinuses due to venous obstruction are described in this paper. Evidence was found in four cases to actin immunoreactivity, and involvement of myofibroblasts was electronmicroscopically observed in one case. Differential diagnosis of vascular transformation of lymph node sinuses is discussed. The lesion is similar to KAPOSI's sarcoma-like subcutaneous processes and to chemodectoma-like bodies in the lung. PMID- 1596482 TI - [Pathomorphological and cytogenetic studies of embryonic abortions]. AB - Cytogenetic studies into abortions have shown that in 50 to 60% of all abortion cases the presence of an aneuploid karyotype can be concluded simply from the histological findings obtained from the abortion sample. This has proved to be important not only for elucidation of the cause of abortion. Also, some cytogenetic studies have provided statistically useful information for counselling on the risk of repetition. However, there are also views according to which the risk of recurrence is not even increased in the wake of aneuploid abortion. Including in our investigation were 528 samples received by routine at the Charite Institute of Pathology from the Charite Obstetric Department, between October 1987 and June 1990. Macroscopic findings included 24 intact amniotic sacs with and 34 without embryonic fragments as well as 188 ruptured amniotic sacs. Only decidual particles were found in 249 cases, while no safe macroscopic assessment was possible of 33 samples. Investigation of the embryos proved to be essential to identification of malformations and determination of discrepancies between gestational age and embryonic development. Correlations were also established between age-specific incidence of abortions and age-specific fertility, with the risk of abortion being found to grow beyond the age of 30 years. Histological parameters recorded from 267 samples revealed links to specific chromosomal aberrations, with 136 of them (50%) being defined as chromosomally induced abortions. Seventeen in 34 abortions on which cytogenetic results had been obtained proved to be aneuploid, among them nine aberrations of trisomal karyotype. A triploid karyotype was exhibited by four and a monosomal karyotype by three. Mosaic was recorded in one case.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596483 TI - [Pulmonary fibrosis after inhalation of amorphous silicic acid]. AB - Light- and scanning electron microscopical studies with energy dispersive x-ray microanalysis were performed on biopsy material obtained from two patients with longstanding occupational exposure to amorphous silica, in whom radiologically interstitial pulmonary fibrosis in vicinity of dust deposits, which could be identified as amorphous and rarely as crystalline silica, was found. The direct topographical relationship between the dust deposits and the tissue reaction indicate that the amorphous silica incorporated in the fibrotic foci is responsible for the development of the fibrosis. PMID- 1596484 TI - Foamy transformed Gaucher cells. AB - Two cases of Gaucher's disease (Types I and III) are described with a substantial part of the storage cell population in several organs (liver, adrenal cortex) intensively vacuolized and transformed into non-specific foam cells. The transformation process encompassed massive three-dimensional distension of the lysosomal system filled with typical lipid tubules as well as severe reduction of the intervening cytoplasm and decrease or disappearance of histochemically detectable enzyme activities, high in typical Gaucher cell (GC). Such an extensive GC foamy transformation may cause diagnostic embarrassment in microscopic interpretation especially of liver biopsies. PMID- 1596485 TI - [Unilateral systematic linear porokeratosis. Immuno- and lectin histochemistry]. AB - An uncommon case of unilateral systemic linear porokeratosis in a women aged 22 years is reported in this paper. The results obtained from frozen-section investigations into lectin binding were indicative of reduced epidermal fucosylation and sialinization beneath the cornoid lamella. The basal stratum failed to react with a polyclonal antibody against calmodulin. Epidermal reaction, with AS-6 staining against urokinase, was of higher intensity. The above findings, as a whole, are likely to suggest accelerated keratinocyte migration to the stratum corneum in cases of linear porokeratosis and and should actually support assignment of the latter to the group of dermatoses with transepidermal elimination. PMID- 1596486 TI - [Granular cell tumor of the vermiform appendix. Case presentation with discussion of histogenesis]. AB - Granular cell tumor is a rare lesion to the appendix. A case of that kind was recorded by the authors from a man, 32 years of age, who underwent surgery for appendicitis. Presence of a granular cell tumor was histologically, histochemically, and immunohistologically verified. Histogenesis of granular cell tumors is not well known, which prompted the authors to summarise some of their recent findings for discussion. PMID- 1596487 TI - [Functional structures of the aorta as a predilection area of the earliest atherosclerotic changes]. AB - Marked lipid deposits selectively localized in the grooves of so-called aortic functional structures were found in a 5-month-old infant who died of rapidly progressing crescentic glomerulonephritis. A prominent nephrotic syndrome comprising hypercholesterolemia and triglyceridemia was present and led to extensive lipid infiltration of the aortic intima. Development of the intimal lesions was probably enhanced by hypertension found in final phase of the illness. Spontaneously enhanced permeability of the intima in the "grooves" and a special constellation of haemodynamic forces along the functional structures were probably responsible for the peculiarly selective localization of lipid deposits that has so far not been described in the literature. PMID- 1596488 TI - [Aneurysm at the base of the brain and tuberous sclerosis]. AB - Reported is the rare case of intracranial aneurysm in a boy aged one year with tuberous sclerosis. Inconspicuous development in the first few months after birth was followed, in the sixth month of age, by aggravating manifestation of convulsive seizures which were clinically diagnosed as tuberous sclerosis. Rapid progression of the clinical pattern was preterminally followed by cerebral haemorrhage which was caused by circumscribed, partially purulent arteritis along with formation of a mycotic aneurysm on the anterior segments of the arterial circle of Willis. The development of this aneurysm is discussed in conjunction with the morphological and clinical findings of tuberous sclerosis. PMID- 1596490 TI - Images of nutrition. PMID- 1596489 TI - [The nephrotoxic effects of single duck immunoglobulins in the triggering of Masugi nephritis]. AB - Studies were conducted into the roles played by various duck immunoglobulins in the anti-basal membrane of nephrotoxic nephritis in rabbit. The 7.8S and 5.7S immunoglobulins which originated from nephrotoxic duck serum were found to be responsible for the development of nephritis in rabbit. No pathogenetic role was played by any other proteins of duck serum. The affinity for the glomerulus basal membrane of 7.8S immunoglobulin was found to be higher than that of 5.7S globulin. As to trigger dosage, nephritis was safely inducted by 10 mg/kg body weight (BW) in the context of 7.8S immunoglobulins and by 15 mg/kg BW in the case of 5.7S immunoglobulins. One and the same morphological nature was recorded from nephritis, no matter by which of the above immunoglobulins it had been caused. Nephrotoxic duck immunoglobulins proved to be highly suitable for induction of experimental glomerulonephritis due to absence from this model of the heterologous phase of nephritis. Hence, the autologous phase is unambiguous and can be examined with higher accuracy. PMID- 1596492 TI - Thermic effect of a meal. 1. Methodology and variation in normal young adults. AB - The variation in the thermic effect of a meal (TEM) was investigated in two groups of five subjects following a standard test meal. Results demonstrated a 50% lower response over 6 h, in the same subjects, when measured intermittently (protocol 2) as compared with a continuous measurement (protocol 1). The variation in TEM among occasions (measured on three occasions in each subject) was large (coefficient of variation (CV) 18.7%, P less than 0.02). However, the post-meal total energy output (CV 1.4%, P greater than 0.05), non-protein respiratory quotient (CV 1.9%, P greater than 0.05) and substrate oxidation rate were not different (P greater than 0.05) in the same individual on separate occasions. Small variations in the basal metabolic rate (BMR) from occasion to occasion (CV 2.6%) contributed to the variation in TEM. However, after allowing for the changes in BMR, variation in TEM (CV 8.6%, P greater than 0.05) was still sizeable though not statistically significant. PMID- 1596491 TI - Weaning practices and breast-feeding duration in Northern Thailand. AB - Current infant feeding guidelines recommend exclusive breast-feeding until the infant is about 4 months old to reduce the risks of early termination of breast feeding, undernutrition and infection. In many societies, however, supplementary foods are given well before 4 months of age. The present paper describes weaning practices, factors associated with early supplementation and the effects of supplementation on duration of breast-feeding in a random sample of sixty northern Thai breast-fed infants studied prospectively from birth to 2 years of age. Composition of supplementary foods, energy and protein intake from supplements and changes in the supplementary diet with increasing infant age are also described. Rice-based foods were given from soon after birth; 81% of the sample had received supplements by 6 weeks of age. Early supplementary feeding was significantly associated with rural residence, large household size, maternal employment in agriculture and maternal age. Girls and infants with lower birth weights tended to be supplemented earlier. Despite early feeding of supplements, breast-feeding was prolonged, with median duration of 12 months. Early introduction of supplements and quantity of supplements consumed in the first 3 months were not associated with duration of breast-feeding. However, mothers who gave infant formula as the first supplementary food stopped breast-feeding slightly earlier, as did younger mothers living in households with more children. PMID- 1596493 TI - Thermic effect of a meal. 2. Role in chronic undernutrition. AB - The thermic effect of a standard liquid meal (TEM; energy 2.5 MJ; containing (g/kg) protein 100, fat 150, carbohydrate 750; volume 350 ml) was measured in a chronically undernourished (UN; n 9) group of human subjects and was compared with results from two control groups, one normal weight (NW)-for-height (BMI greater than 20; n 10) and the other underweight (UW)-for-height (BMI less than 18, n 10), using a ventilated-hood system over a period of 6 h after ingestion of the meal. Results indicated that the UN subjects had lower values for body weight, height, percentage fat and fat-free mass (FFM) compared with those of either control group. Basal metabolic rates were lowest in the UN group in absolute terms; however, there were no significant differences among groups on an analysis of covariance (ANACOVA) with FFM as the covariate. TEM responses in the UN group were significantly higher when expressed either in absolute terms or as a percentage of the energy density of the meal. The post-meal total energy output was significantly lower (P less than 0.05) in the UW and UN groups as compared with the NW group in absolute terms; however, on adjusting for differences in FFM (by ANACOVA) there were no significant differences among groups. This would suggest that in the chronically undernourished thermogenic responses to a meal are unlikely to contribute towards any energy saving and may not constitute a part of any adaptive response to the undernourished state. PMID- 1596494 TI - Thermic effect of a meal. 3. Effect of dietary supplementation in chronically undernourished human subjects. AB - Five apparently healthy, chronically undernourished (UN) male volunteers aged between 18 and 30 years were studied before and after 12 weeks of dietary supplementation. The thermic effect of a meal (TEM) was measured over a period of 6 h using a ventilated-hood system. Results indicated a significant increase in body-weight after supplementation due to increases in body fat and fat-free mass (FFM) in the proportion of 69% and 31% respectively. The basal metabolic rates (BMR) measured post supplementation were significantly higher in absolute terms, with a trend towards higher values when adjusted for the changes in FFM. TEM responses measured after 12 weeks of supplementation were significantly lower when expressed either in absolute terms (presupplementation 227.0 kJ v. post supplementation 193.5 kJ), or as a percentage of the energy density of the meal (9.1% v. 7.7%). This lower TEM was reciprocal to the changes in the BMR (r 0.86). The post-meal total energy output (PMTEO) was, however, not significantly different after 12 weeks of dietary supplementation. The unchanged PMTEO would indicate an unaltered 'thermogenic capacity', following supplementation, in these chronically undernourished subjects. These results confirm our earlier conclusion that, in chronic undernutrition, the thermic response to a meal may not contribute to any energy saving. PMID- 1596495 TI - Energy and nitrogen intake, expenditure and retention at 32 degrees in growing fowl given diets with a wide range of energy and protein contents. AB - Heat production (HP) and the intake and retention of energy and nitrogen were measured in growing broiler fowl kept at 32 degrees and given diets with metabolizable energy contents from 8 to 15 MJ/kg and crude protein (N x 6.25; CP) contents of 130 and 210 g/kg. The temperature of 32 degrees was chosen for comparison with earlier measurements at 20 degrees to minimize heat produced for the maintenance of body temperature. The effects of diet composition were observed when the same birds were taken from 20 to 32 degrees. The tendency for energy intake to increase with dietary energy concentration was less at 32 than at 20 degrees. The lower heat increments measured for the high-fat diets did not, therefore, confer an increased ability to sustain higher energy intake at 32 degrees. HP was about 17% lower at 32 than at 20 degrees; the change in HP between 20 and 32 degrees was not significantly influenced by diet composition. The absence of significant effects of diet composition on HP, combined with the significant trend in energy intake, produced significant differences (related both to dietary energy and dietary protein concentrations) in total energy retention and in the partition of retained energy between protein and fat. As at 20 degrees, variation in energy retention and in the composition of retained energy were the main responses to variation in dietary CP concentration and energy intake; a significantly higher energy cost of unit protein accretion on the low-CP diets was insufficient to produce an elevation in total HP because the higher unit energy cost was balanced by a lower absolute rate of protein accretion. PMID- 1596496 TI - The metabolic utilization of amino acids: potentials of 14CO2 breath test measurements. AB - The present paper offers a dual 14CO2 breath test approach to study the metabolic utilization of free amino acids in the body. Using the carboxyl-[14C]isotopomer of an amino acid as the test substrate the percentage recovery of the isotope as 14CO2 reflects which part of the labelled amino acid flux has been decarboxylated. The residual C fragments may flow to total oxidation at least to the level recovered for the universal [14C]isotopomer. In the case that recovery for total oxidation is less than for decarboxylation, part of the [14C]fragments are retained in the body by either exchange or non-oxidative pathways. Utilization of tyrosine and leucine was measured in the post-absorptive phase in adult rats, conditioned on isoenergetic diets containing 210, 75 or 0 g protein/kg. It was shown that the level of dietary protein exerts an influence on both decarboxylation and total oxidation. Although the responses of leucine and tyrosine were not different for total oxidation, there was a difference between the amino acids in their relative rate of decarboxylation. That this dual 14CO2 breath test approach can be used as a tool to evaluate whether the protein and amino acid supply has been adequate to support actual requirements is discussed. PMID- 1596497 TI - Inhibitory effect of high protein intake on nephrocalcinogenesis in female rats. AB - Increased intakes of protein have been shown to reduce kidney calcification (nephrocalcinosis) in female rats. Two questions were addressed in the present study. First, can protein-induced inhibition of nephrocalcinosis be demonstrated when the diets used are balanced for calcium, magnesium and phosphorus in the added protein? Second, can the protein effect be explained by the frequently observed magnesiuria after giving high-protein diets? Nephrocalcinosis was induced in female rats by giving purified diets containing 151 g casein/kg and either an increased concentration of P (6 v. 2 g/kg) or a decreased concentration of Mg (0.1 v. 0.4 g/kg). To these diets 151 g ovalbumin/kg was added at the expense of glucose, and the diets were balanced for Ca, Mg and P in ovalbumin. The diets were given for 29 d. In rats fed on the diet containing 151 g protein/kg, an increased intake of P or a decreased intake of Mg caused nephrocalcinosis as measured chemically by analysis of kidney Ca as well as histologically by scoring kidney sections stained according to Von Kossa's method. The addition of ovalbumin to the diet prevented the induction of nephrocalcinosis. High P intake and low Mg intake with the low-protein diets induced enhanced loss of albumin in urine, suggesting that nephrocalcinosis caused kidney damage. Increased protein intake with a non-calcinogenic diet also caused increased albumin excretion in urine. Irrespective of the composition of the background diet, increased protein intake caused increased urinary excretion of Mg. When all dietary groups were considered, differences in nephrocalcinosis and urinary Mg output were not proportionally related. PMID- 1596498 TI - Effect of dietary proteins on insulin-like growth factor-1 (IGF-1) messenger ribonucleic acid content in rat liver. AB - Effects of quantity and quality of dietary proteins on plasma immunoreactive insulin-like growth factor-1 (IGF-1) concentration, and content of IGF-1 mRNA in rat liver were investigated in rats. Plasma immunoreactive IGF-1 concentration in rats given a casein diet was higher than that in rats given a soya-bean-protein or protein-free diet. The IGF-1 mRNA content in liver was estimated by the Northern blot hybridization technique employing 32P-labelled rat IGF-1 complementary DNA (cDNA). At least four molecular species of IGF-1 mRNA of different molecular weight were found in rat liver. The sizes were 0.8-1.2, 2.0, 3.6-4.0 and 7.4 kb. Most of the mRNA species decreased in the livers of rats given a gluten diet (120 g gluten/kg diet) compared with rats given the casein diet. In particular, mRNA of 7.4 kb decreased markedly. When rats were fed on the protein-free diet, mRNA of all species decreased significantly. The estimated IGF 1 mRNA in the livers of rats fed on the gluten or protein-free diet was almost 0.4 of that of the rats given the casein diet. Feeding the soya-bean-protein diet did not result in a marked effect on the hepatic content of mRNA species of IGF 1. The results showed that liver IGF-1 mRNA content is sensitively regulated by quantity and nutritional quality of dietary proteins. PMID- 1596499 TI - Dietary-induced increases of disaccharidase activities in rat jejunum. AB - A study was carried out to examine whether the responsiveness of small intestinal epithelial cells to dietary carbohydrate varied during the daily 24 h cycle. The effect of sucrose on disaccharidase activities was compared during a period of decreasing disaccharidase activities, i.e. between 22.00 and 10.00 hours, and increasing disaccharidase activities, i.e. between 10.00 and 22.00 hours, in the jejunum of 7-week-old-rats. Rats were fed on a low-starch, high-fat diet (Lst; starch 5 and fat 73% of gross energy), or a high-starch, low-fat diet (Hst; starch 70 and fat 7% of gross energy). Both dietary groups exhibited typical diurnal variations in jejunal sucrase (EC 3.2.1.48), maltase (EC 3.2.1.20) and lactase (EC 3.2.1.23) activities, exhibiting a peak around 22.00 hours and a trough at approximately 10.00 hours. When rats were fed on diet Lst for 7 d and then force-fed on an isoenergetic sucrose diet (S; sucrose 40 and fat 37% of gross energy) for 6 or 12 h they exhibited increased sucrase, maltase and lactase activities compared with rats fed on diet Lst. The absolute increase in disaccharidase activities was similar regardless of the time diet S was given or whether rats were killed at 10.00 hours or at 22.00 hours. Analyses of sucrase and lactase activities along the villus-crypt columns showed that the distribution of cell cohorts that responded to diet S was not influenced by the time of introduction of diet S. These findings suggest that small intestinal epithelial cells possess the ability to respond to dietary carbohydrate throughout the daily 24 h cycle. PMID- 1596500 TI - The effect of malnutrition on insulin binding to rat erythrocytes. AB - Insulin binding to erythrocyte receptors was compared in malnourished and control rats. Percentage specific insulin binding to malnourished rat erythrocytes was significantly lower than to control erythrocytes (P less than 0.001). The low insulin binding in the malnourished rat erythrocytes was accompanied by low insulin receptor affinity (P = 0.035). PMID- 1596501 TI - Supplementation with wheat selenium induces a dose-dependent response in serum and urine of a Se-replete population. AB - In spite of a rather modest dietary intake of selenium (80 micrograms/10 MJ), Norwegian serum Se levels are among the highest in Europe. As part of an ongoing study of Se bioavailability, effects of different doses of wheat Se were investigated in eighteen healthy, Norwegian women. The participants were given Se rich bread providing 100, 200 and 300 micrograms Se daily for 6 weeks. About 50% of the Se intake was excreted in the urine by week 6, compared with 67% before the intervention started. Serum Se increased by 20, 37 and 53 micrograms/l respectively, in the three group (P less than 0.001). The blood response and renal clearance results compare well with data obtained from less Se-replete populations, and support the hypothesis that selenomethionine from the diet is incorporated into a non-specific amino acid pool. Our study indicates that the intake of wheat Se is the main determinant of blood Se levels in Norway. PMID- 1596502 TI - Mineral excretion of rats fed on diets containing faba beans (Vicia faba L.) or faba bean fractions. AB - The effects on faecal mineral excretion of two commercial varieties (local cultivar and Troy cultivar) of raw faba beans (Vicia faba L., minor) meal (VFM) and its fractions have been studied in growing rats. Diets contained local-VFM (dark seed coat) and Troy-VFM (light seed coat) at 474-500 g/kg diet, hull (VFH) from both varieties at 65 g/kg diet, and the insoluble cotyledon residue (VFCR) obtained from the Troy variety at 237 g/kg diet. Rats were pair-fed on diets which had been supplemented with amino acids to target requirements and contained similar amounts of zinc, manganese, iron and copper. With VFM diets the apparent absorption of Zn and Mn was significantly reduced. On the other hand, with hulls the apparent absorption of Fe was reduced while that of Cu slightly increased. As the amounts of calcium, phosphorus and magnesium in VFM and VFH diets were higher than in the controls, the increased intake resulted in a significant increase in both the apparent absorption and the faecal excretion of these minerals. The inclusion of VFCR in the diet had no significant effect on the mineral content of faeces. The relatively low concentrations of phytate in the bean seeds of 7.8 and 6.7 g/kg for the local and Troy cultivars respectively, could not adequately account for the increased mineral excretion. The results suggest that other seed constituents, possibly the soluble non-starch polysaccharides, may be involved in the elevated loss of Zn and Mn in rats fed on diets containing faba bean for extended periods, while some insoluble structural hull components may interfere with the absorption of Fe from the gut. PMID- 1596503 TI - Protein sorting between mitochondrial outer and inner membranes. Insertion of an outer membrane protein into the inner membrane. AB - The amino terminal 29 amino acids of the outer mitochondrial membrane protein of yeast, OMM70 (MAS70), consisting of the targeting and membrane anchor domains, has been fused to a reporter protein, dihydrofolate reductase. The hybrid protein, designated pOMD29, was efficiently imported into the outer membrane of rat heart mitochondria by a process dependent on ATP and proteinase-sensitive components on the surface of the organelle, and in which the orientation of the native protein was retained. To determine if the protein translocation machinery of the inner membrane is also capable of recognizing and inserting pOMD29, direct access to the intermembrane space was provided to pOMD29 by selectively rupturing the mitochondrial outer membrane by osmotic shock. In this system, the outer membrane binding site for matrix-destined precursor proteins can be bypassed, and efficient import restored to proteinase-pretreated mitochondria. pOMD29 was imported into the inner membrane of osmotically-shocked mitochondria, mediated by protein components. The outer membrane orientation of pOMD29 was conserved when inserted into the inner membrane but, unlike the outer membrane, import into the inner membrane required delta psi. We conclude that the protein translocation machinery of the mitochondrial inner membrane is capable of recognizing and inserting a protein whose topogenic information otherwise results in insertion of the protein to the outer membrane. The significance of these findings for sorting of proteins between the mitochondrial inner and outer membranes is discussed. PMID- 1596504 TI - Interdigitated bilayer packing motifs: Raman spectroscopic studies of the eutectic phase behavior of the 1-stearoyl-2 caprylphosphatidylcholine/dimyristoylphosphatidylcholine binary mixture. AB - The thermotropic properties and acyl chain packing characteristics of multilamellar dispersions of binary mixtures of 1-stearoyl-2 caprylphosphatidylcholine (C(18):C(10)PC), an asymmetric chain species, and dimyristoylphosphatidylcholine (C(14):C(14)PC), a symmetric chain lipid, were monitored by vibrational Raman spectroscopy. In order to examine each component of the binary mixture separately, the acyl chains of the symmetric chain species were perdeuterated. As shown by differential scanning calorimetry, the mismatch in the gel phase bilayer thickness between the two lipid components generates a lateral phase separation resulting in two distinct gel phases, G(I) and G(II), which coexist over much of the composition range. The Raman data demonstrate that the mixed interdigitated phase (three chains per headgroup), analogous to single component phase behavior, is retained when the C(18):C(10)PC component act as a host for the G(I) gel phase. In contrast, the C(18):C(10)PC molecules exhibit partial interdigitation (two chains per headgroup) when they are included as guests within the C(14):C(14)PC host matrix to form the G(II) gel phase. Compared to pure C(14):C(14)PC bilayers at equivalent reduced temperatures, the host G(II) gel phase C(14):C(14)PC molecules exhibit an increased acyl chain order, while for the host G(I) gel phase the C(14):C(14)PC lipid species show increased intrachain disorder. PMID- 1596505 TI - Interfacial pH modulation of membrane protein function in vivo. Effect of anionic phospholipids. AB - In yeast cells, the magnitude of the membrane surface potential (phi) is determined to a large extent by the relative amount of anionic phospholipids (Cerbon and Calderon (1990) Biochim. Biophys. Acta 1028, 261-267). When a significant surface potential exists, the pH at the membrane surface (interfacial pH) will be different to that in the bulk suspending medium. We now report that: (1) In cells with higher phi (phosphatidylinositol-rich cells (PI-rich) and phosphatidylserine-rich cells (PS-rich) a 10-times lower proton concentration in the bulk was enough to achieve the maximum transport activity of H(+)-linked transport systems when compared to normal cells. (2) When the phi was reduced by increasing the concentration of cations in the medium, more protons were required to achieve maximum transport, that is, the pH activity curves shifted downwards to a more acidic pH. (3) The magnitude of the downward pH shift was around 2.5 times higher for the more charged membranes. (4) Around 10-times more KCl than MgCl2 was necessary to give an equivalent pH shift, in agreement with their capacity to reduce the phi of artificial bilayers. The interfacial pH calculated from the values of phi indicates that it was 0.4 pH units lower in the anionic phospholipid rich cells as compared to normal cells. The results indicate that membrane surface potential may explain the complex relationship between pH, ionic strength and membrane protein function. Maximum transport activities were found for glutamate at interfacial pH of 4.2-4.8 and were inhibited at interfacial pH = 3.2-3.4, suggesting that surface groups of the carrier proteins with pK values in the region 3.8-4.2 (aspartyl and glutamyl) are involved in binding and/or release of charged substrates. PMID- 1596507 TI - Molecular packing parameters of bipolar lipids. AB - The bipolar lipid fractions extracted from the thermophilic archaeobacterium Sulfolobus solfataricus have different chemical structures and geometrical shapes. The conditions which lead to the formation of vesicles were investigated in order to study the self-assembly of these molecules. Such conditions are fulfilled when an appropriate mixture of two different molecular species (both bipolar or bipolar and monopolar) is used. According to the theory introduced by Israelachvili and co-workers, lipid self-assembly results from the balance of interaction free energy, entropy and molecular geometry. We have shown that this theory can be extended to bipolar lipids, in spite of their more complex nature, and the experimental results obtained combining 1H-NMR, light scattering and entrapped volume techniques closely match theoretical expectations. To carry out calculations, it was necessary to introduce hypotheses about the disposition of bipolar molecules in the vesicle membrane. These hypotheses have been tested indirectly by measuring the transport properties mediated by carriers or channels, whose transport mechanism can be considered to be a probe of the membrane structure. PMID- 1596506 TI - Uptake of L-leucine and L-phenylalanine across the basolateral cell surface in isolated oxyntic glands. AB - The time course, kinetic, specificity and sodium-dependence of L-leucine and L phenylalanine uptake by rabbit isolated oxyntic glands were studied in order to identify the systems involved in the transport of branched-chain and aromatic neutral amino acids through the basolateral cell membrane. The uptake was measured directly in the disrupted cells after incubation of the glands with the 3H-labelled amino acid both in a sodium-containing and a sodium-free medium. The uptake of L-leucine was largely carrier-mediated whilst L-phenylalanine was taken up by either carrier-mediated and nonsaturable processes. Both amino acids were taken up by a Na(+)-independent process. The kinetic parameters of L-leucine and L-phenylalanine carrier-mediated influx were, respectively: Kt = 2.71 mM and Jmax = 1390 nmol mg-1 s-1, Kt = 1.03 mM and Jmax = 176 nmol mg-1 s-1. From cross inhibition studies it can be inferred that L-leucine is primarily transported by a Na(+)-independent system which shows specificity for bulky side chains dipolar amino acids. The system displays similar affinities for L-phenylalanine (Ki = 2.81 mM) and L-isoleucine (Ki = 2.62 mM). Similar results were obtained from self inhibition experiments: the Ki of the carrier-mediated uptake of L-leucine and L phenylalanine were 2.12 and 2.40 mM (from a Hanes plot) or 3.2 and 0.8 mM (from a Dixon plot), respectively. It is concluded that a sodium-independent transport system, like Christensen's 'L' type, is shared by branched-chain and aromatic dipolar amino acids, which only shows slight differences in their affinities for the carrier. PMID- 1596508 TI - Interaction of retinol and retinoic acid with phospholipid membranes. A differential scanning calorimetry study. AB - The influence of retinol and retinoic acid, two retinoids of major interest, on the main gel to liquid-crystalline phase transition of different phospholipid membranes has been studied by means of differential scanning calorimetry. Both compounds exerted perturbing effects on the phase transition of membranes composed of dipalmitoylphosphatidylcholine or dipalmitoylphosphatidylethanolamine. At concentrations up to 42.5 mol% of retinoid in the membrane, the delta H was not much affected with respect to the pure phospholipid, indicating a rather slight interaction. As the concentration of retinol was increased the Tc transition temperature decreased. A fluid-phase immiscibility was observed for the system DPPC/retinol at concentrations between 0 and 33 mol%. Almost ideal phase diagrams were obtained for the mixture DPPE/retinol. At concentrations of 33 mol% and higher retinol was able to induce phase separations in DPPC membranes, but not in DPPE. The effect of retinoic acid was much weaker, the Tc and delta H remaining almost unaltered and equal to that of the pure phospholipid up to concentrations of 30 mol%, at neutral pH. Retinoic acid exerted a pH-dependent effect. As the pH decreased, and therefore increased the extent of protonation of retinoic acid, the pertubation of the membrane induced by this compound was less. A strong effect, both on Tc and delta H, was observed at pH 10, where the retinoic acid moiety will be mainly unprotonated and the negative charge will generate repulsive forces thus destabilizing the membrane. The mixture DPPC/retinoic acid presents a region of fluid-phase immiscibility. At low pH, when the retinoic acid moiety was fully protonated, this fluid-immiscibility region extended from 0 to 36 mol% of retinoic acid, but its size decreased with increasing pH, and at pH 10 it was only found from 0 to 3 mol%. These results are discussed in terms of the possible retinoid/phospholipid interactions and the disposition of the retinoid moiety in the bilayer. PMID- 1596509 TI - Nucleoside transport in cultured LLC-PK1 epithelia. AB - The transport of nucleosides by LLC-PK1 cells, a continuous epithelial cell line derived from pig kidney, was characterised. Uridine influx was saturable (apparent Km approximately 34 microM at 22 degrees C) and inhibited by greater than 95% by nitrobenzylthioinosine (NBMPR), dilazep and a variety of purine and pyrimidine nucleosides. In contrast to other cultured animal cells, the NBMPR sensitive nucleoside transporter in LLC-PK1 cells exhibited both a high affinity for cytidine (apparent Ki approximately 65 microM for influx) and differential 'mobility' of the carrier (the kinetic parameters of equilibrium exchange of formycin B are greater than those for formycin B influx). An additional minor component of sodium-dependent uridine influx in LLC-PK1 cells became detectable when the NBMPR-sensitive nucleoside transporter was blocked by the presence of 10 microM NBMPR. This active transport system was inhibited by adenosine, inosine and guanosine but thymidine and cytidine were without effect, inhibition properties identical to the N1 sodium-dependent nucleoside carrier in bovine renal outer cortical brush-border membrane vesicles (Williams and Jarvis (1991) Biochem. J. 274, 27-33). Late proximal tubule brush-border membrane vesicles of porcine kidney were shown to have a much reduced Na(+)-dependent uridine uptake activity compared to early proximal tubule porcine brush-border membrane vesicles. These results, together with the recent suggestion of the late proximal tubular origin of LLC-PK1 cells, suggest that in vivo nucleoside transport across the late proximal tubule cell may proceed mainly via a facilitated-diffusion process. PMID- 1596510 TI - Uptake of tyramine cellobiose by rat liver. AB - The uptake of 125I-tyramine cellobiose (TC) by isolated rat hepatocytes and by total rat liver is markedly higher than that of 14C-sucrose and 125I-PVP, suggesting that TC does not enter the cells by fluid phase endocytosis. The distribution of radioactivity after differential centrifugation shows that the compound is shared out amongst sedimentable structures and unsedimentable fraction. Analysis by isopycnic centrifugation indicates that quickly after its penetration into the cells, most of sedimentable 125I-TC is associated with lysosomes. Such an intracellular localization is confirmed by the distributions observed after free flow electrophoresis and by the fact that radioactivity and cathepsin C, a lysosomal hydrolase, are simultaneously released from a mitochondrial fraction treated with glycyl-L-phenylalanine-2-naphthylamide. Pretreatment of the rats with chloroquine, an acidotropic drug that accumulates in lysosomes, prevents to some extent the entry of 125I-TC into these organelles. Experiments performed with purified lysosomes show that 14C-sucrose does not cross the lysosomal membrane when 125I-TC accumulates linearly with time in the fractions. These results are explained by supposing that the linkage of tyramine to cellobiose allow the disaccharide to diffuse through the plasma and the lysosome membranes, and that the accumulation of the molecule in these organelles results from its weak basic properties. 125I-TC could be an interesting molecule with which to study acidotropism in the whole animal and in isolated and cultured cells. PMID- 1596511 TI - Effect of bacteriorhodopsin on the orientation of the headgroup of 1,2 dimyristoyl-sn-glycero-3-phosphocholine in bilayers: a 31P- and 2H-NMR study. AB - Bacteriorhodopsin (BR), purified from the halophilic bacterium, Halobacterium halobium, has been separated from the endogenous purple membrane lipids and reconstituted by detergent dialysis into bilayers of the zwitterionic phospholipid, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), which was selectively deuterated at the headgroup in the choline alpha- and beta-methylene segments and the choline gamma-methyl groups. Complexes of DMPC/BR contents from 67:1 to 222:1 (mol/mol) were produced under conditions to promote formation of large vesicles (mean diameters 600-700 nm). The magnitudes of the 2H-NMR quadrupole splittings recorded from the deuterium-labelled headgroup segments, and the 31P-NMR chemical shift anisotropy (CSA) of the phosphate group appeared to vary linearly with the BR content in the complexes over the range of DMPC/BR ratios studied. On increasing the proportion of BR in the DMPC-BR complexes, the 2H-NMR quadrupole splittings measured from the choline gamma-methyl groups and the beta-methylene segments and the 31P-NMR CSA increased in magnitude, while the 2H-NMR quadrupole splitting from the alpha-methylene segment decreased. Such opposing changes in the choline alpha- and beta-methylene segment quadrupole splittings are similar to those reported on increasing the proportion of positively charged amphiphile at the bilayer surface (Seelig et al. (1987) Biochemistry 26, 7535-7541). It is suggested that BR presents a net positive charge to the phosphocholine headgroups at the protein/lipid interface. PMID- 1596512 TI - Effects of local anesthetics on the Chara plasmalemma. AB - The effects of lidocaine, tetracaine, procaine and bupivacaine (less than 1000 microM) on the Chara corallina internodal cell were studied. These local anesthetics depolarized the membrane at rest, while they affected the rising phase and the peak level of action potential not appreciably. Instead, they prolonged the time course of the falling phase of action potential as slowly as the repolarization was imperfect, even after enough lapse beyond the refractory period. Consequently, an action potential appeared to enhance the degree of depolarization at rest. Such a depolarization with stimulus/excitation was named use-dependent depolarization, while the depolarization without excitation, the resting one. The order of the potency of the use-dependent depolarization almost coincided with that of the nerve-blocking potency. During depolarization the change in membrane conductance was not simple. However, the conductance-voltage (Gm-Vm) relationship curve in the presence of local anesthetic suggested that depolarization was due to, not only the decrease in the electrogenic H(+)-pump, but also the increase in the diffusion conductance. PMID- 1596513 TI - Alcohol interaction with high entropy states of macromolecules: critical temperature hypothesis for anesthesia cutoff. AB - Nerve excitation generates heat and decreases the entropy (review by Ritchie and Keynes (1985) Q. Rev. Biophys. 18, 451-476). The data suggest the existence of at least two thermodynamically identifiable states: resting and excited, with a thermotropic transition between the two. We envision that nerve excitation is a transition between the two states of the excitation machinery consisting of proteins and lipids, rather than the sodium channel protein alone. Presumably, both proteins and lipids change their conformation at excitation. We proposed (Kaminoh et al. (1991) Ann. N.Y. Acad. Sci. 625, 315-317) that anesthesia occurs when compounds have a higher affinity to the resting state than to the excited state of excitable membranes, and that there is a critical temperature above which the affinity to the excited state becomes greater than to the resting state. When the temperature exceeds this critical level, compounds lose their anesthetic potency. We used thermotropic phase-transition of macromolecules as a model for the excitation process. Anesthetic alcohols decreased the main transition temperature of dipalmitoylphosphatidylcholine (DPPC) membranes and also the temperature of the alpha-helix to beta-sheet transition of poly(L lysine). The affinity of alcohols to the high- and low-temperature states of the DPPC membranes were separately estimated. The difference in the affinity of n alcohols to the liquid (high-temperature) and solid (low-temperature) states correlated with their anesthetic potency. It is not the total number of bound anesthetic molecules that determines the anesthesia, rather, the difference in the affinity between the higher and lower entropy states determines the effects. The critical temperatures of the long-chain alcohols were found to be lower than those of the short-chain alcohols. Cutoff occurs when the critical temperature of long-chain alcohols is below the physiological temperature, such that the anesthetic potency is not manifested in the experimental temperature range. PMID- 1596514 TI - Dietary fatty acids and dietary cholesterol differ in their effect on the in vivo regulation of apolipoprotein A-I and A-II gene expression in inbred strains of mice. AB - Dietary cholesterol and dietary saturated fatty acids affected the plasma concentrations of various HDL components and the hepatic and intestinal expression of the apolipoprotein (apo) A-I gene and the hepatic expression of the A-II gene differently in three inbred strains of female mice. Thus, the HC diet (0.5% cholesterol, no added fatty acids) decreased HDL-cholesterol in C57BL and SWR strains but not in the C3H strain; plasma apo A-I and apo A-II concentrations decreased in all three strains. HDL-C/apo A-I and apo A-I/apo A-II mass ratios increased, suggesting that the HC diet altered both the concentrations and the compositions of HDL particles. In contrast, the HF diet (20% hydrogenated coconut oil, no added cholesterol) increased HDL cholesterol and apo A-I concentrations. The combination diet (HF/C, 20% coconut oil plus 0.5% cholesterol) increased HDL cholesterol and decreased triacylglycerols. Apo A-I concentrations were unaltered except for a significant increase in SWR mice. Apo A-II concentrations decreased in all strains. To examine molecular events that could lead to the changes in plasma apo A-I and apo A-II, we measured transcription rates in hepatic nuclei and steady state mRNA concentrations in liver and intestine and apo A-I synthetic rates in liver. Dietary cholesterol and fatty acids produced differing effects at transcriptional as well as post-transcriptional loci and the changes differed according to mouse strain. The most pronounced strain-related differences for both apo A-I and apo A-II occurred at post-transcriptional loci of apoprotein production. These could represent altered rates of translation in, or secretion from liver and/or intestine, or altered rates of clearance from plasma. In conclusion, the regulation of apo A-I and apo A-II gene expression by diet occurs at several steps of their production and perhaps also in catabolic pathways. This study identifies potential loci of regulation and forms the basis for future studies investigating specific genetic and molecular regulatory mechanisms. PMID- 1596515 TI - Characteristics and subcellular localization of pristanoyl-CoA synthetase in rat liver. AB - We have investigated the activation of pristanic acid to its CoA-ester in rat liver. The results show that peroxisomes, mitochondria as well as microsomes contain pristanoyl-CoA synthetase activity. On the basis of competition experiments and immunoprecipitation studies using antibodies raised against rat liver microsomal long-chain fatty acyl-CoA synthetase (EC 6.2.1.3) we conclude that pristanic acid is activated by the same enzyme which activates long-chain fatty acids, i.e., long-chain fatty acyl-CoA synthetase. PMID- 1596517 TI - The effects of season and exercise on the levels of plasma polyunsaturated fatty acids and lipoprotein cholesterol in young rats. AB - Plasma concentrations of polyunsaturated fatty acids (20:4(n - 6), 20:5(n - 3), 22:6(n - 3)) and high- or low-density lipoprotein cholesterols (HDL-C, LDL-C) in young rats were measured to elucidate a possible relationship between the levels of [20:5(n - 3)] [20:4(n - 6)]-1, [22:6(n - 3)] [20:4(n - 6)]-1 and [LDL-C] [HDL C]-1. Seasonal change in [LDL-C] [HDL-C]-1 in the sedentary and exercised rats was found to correlate with the respective values of [20:5(n - 3)] [20:4(n - 6)] 1 and/or [22:6(n - 3)] [20:4(n - 6)]-1. Moderate exercise in summer decreased plasma arachidonic acid (20:4(n - 6)). With the decrement of the 20:4(n - 6) acid, the ratios of [20:5(n - 3)] [20:4(n - 6)]-1 and [22:6(n - 3)] [20:4(n - 6)] 1 increased to a greater degree. The [LDL-C] [HDL-C]-1 values in this case were inversely associated with the levels of [22:6(n - 3)] [20:4(n - 6)]-1. We therefore suggest that moderate physical training in summer protects arteries from thrombogenesis and lipid accumulation. PMID- 1596516 TI - Arachidonic acid metabolism in isolated pancreatic islets. VI. Carbohydrate insulin secretagogues must be metabolized to induce eicosanoid release. AB - Pancreatic islets stimulated with D-glucose are known to liberate arachidonic acid from membrane phospholipids and release prostaglandin E2 (PGE2). A component of the eicosanoid release induced by D-glucose has been demonstrated to occur without calcium influx and must be triggered by other coupling mechanisms. In this study, we have attempted to identify mechanisms other than calcium influx which might couple D-glucose stimulation to hydrolysis of arachidonate from membrane phospholipids in islet cells. We have found that occupancy of the beta cell plasma membrane D-glucose transporter is insufficient and that D-glucose metabolism is required to induce islet PGE2 release because 3-O-methylglucose fails to induce and mannoheptulose prevents PGE2 release otherwise induced by 17 mM D-glucose. The carbohydrate insulin secretagogues mannose and D-glyceraldehyde have also been found to induce islet PGE2 release, but the non-secretagogue carbohydrates L-glucose and lactate do not. Carbohydrate secretagogues are known to be metabolized to yield ATP and induce depolarization of the beta cell plasma membrane. We have found that depolarization by 40 mM KCl induces PGE2 release only in the presence and not in the absence of extracellular calcium, but exogenous ATP induces islet PGE2 release with or without extracellular calcium. Carbachol is demonstrated here to interact synergistically with increasing concentrations of glucose to amplify PGE2 release and insulin secretion. Pertussis toxin treatment is shown here not to prevent PGE2 release induced by glucose or carbachol but to increase the basal rate of PGE2 release and the islet cyclic AMP content. Theophylline (10 mM) exerts similar effects. Eicosanoid release in pancreatic islets can thus be activated by multiple pathways including muscarinic receptor occupancy, calcium influx, increasing cAMP content, and a metabolic signal derived from nutrient secretagogues, such as ATP. PMID- 1596518 TI - Changes in particle size of high density lipoproteins during incubation with very low density lipoproteins, cholesteryl ester transfer protein and lipoprotein lipase. AB - Previous reports have produced conflicting views of the effects of lipoprotein lipase (LPL) on the particle size distribution of high density lipoproteins (HDL). In this study we have investigated the changes in particle size of HDL promoted by the interaction of LPL, the cholesteryl ester transfer protein (CETP) and very low density lipoproteins (VLDL). When the plasma fraction of d less than 1.21 g/ml (containing all lipoprotein fractions) was incubated for 24 h with bovine milk LPL alone or with CETP alone, there was relatively little change in the particle size distribution of HDL. When both LPL and CETP were added to the lipoprotein mixture, there was a substantial reduction in the particle size of HDL. This reduction in HDL particle size was found to be a direct function of the concentration of CETP. It was also influenced by the concentrations of VLDL and LPL, although in these cases the relationships were complex. When mixtures of the plasma fraction of d = 1.006-1.21 g/ml (this fraction includes low density lipoproteins and HDL but not VLDL) were supplemented with both LPL and CETP and incubated in the presence of varying concentrations of added VLDL, there was a progressive increase in the conversion of HDL into very small HDL particles of radius 3.7 nm as the concentration of VLDL triacylglycerol increased up to about 400 nmol/nml. However, further increases in the concentration of VLDL were accompanied by a progressive reduction in the formation of small HDL particles until, at higher VLDL concentrations, the effect was all but abolished. There was a similar enhancement in the formation of small HDL when LPL was added at low but not at high concentrations. These findings are consistent with the existence of two opposing processes. On the one hand there is likely to be a synergism between CETP and the non-esterified fatty acids (NEFA) released by LPL; this will favour a reduction in HDL particle size. On the other hand, the transfer of lipolysis products from VLDL to HDL may mask any such particle size reduction. The fact that the reduction in HDL particle size promoted by LPL, CETP and VLDL was found to be all but abolished by adding fatty acid-poor albumin to the incubation mixture is consistent with the proposition that NEFA are involved in the process. It also suggests, however, that the phenomenon may have little if any physiological significance. PMID- 1596519 TI - Heterogeneity of arachidonate and paf-acether precursor pools in mast cells. AB - In mammalian cells, arachidonate release and paf-acether formation are frequently associated. The alkyl-acyl-GPC has been proposed as an important source for released arachidonic acid and arachidonate-containing alkylacyl-GPC species as unique precursor for paf-acether. However, the specificity of precursor pools either concerning arachidonic acid or paf-acether is still a matter of controversy. We studied the relationship between the precursor pools for both autacoids in antigenically-stimulated cultured mast cells. We took advantage of the particular arachidonate turnover rate in each phospholipid to investigate the role of alkyl-arachidonyl-GPC in the supply of arachidonic acid by using newly and previously [14C]arachidonate-labeled cells. The specific activity of the released arachidonate was reduced 2-fold following overnight cell incubation, whereas labeling in alkyl-arachidonoyl-GPC was only slightly modified and never corresponded to that of released arachidonate when newly or previously labeled cells were triggered with the antigen. These results are not in favor of a major role for alkyl-arachidonoyl-GPC in supplying arachidonate. In contrast, by using previously labeled cells, we demonstrated that all arachidonate-containing phospholipids were involved in the release of arachidonic acid. The pattern of alkyl chains in alkyl-arachidonoyl-GPC, as well as in total alkylacyl-GPC, is unique since it consists mainly of 18:1 (more than 55%), whereas the 16:0 represents only about 30% of total alkyl chains. Therefore, we analyzed paf acether molecular composition in order to compare it to the alkyl composition of the precursor pools. The content in 18:1 species of paf-acether, as measured by bioassay (aggregation of rabbit platelets), was always lower than that of 16:0 species and then did not correspond to the alkyl composition of the precursor. These data suggest that the enzymes involved in paf synthesis might be specific for 16:0 alkyl chains of precursor pool. PMID- 1596520 TI - Theoretical analysis of lipid transport in sciatic nerve. AB - We modify our previous mathematical model of axonal transport to analyze data on the fast transport of lipids in rat sciatic nerve given in Toews et al. (J. Neurochem. 40, 555-562 (1983)). The theoretical model accounts well for the shapes of the profiles of phosphatidylcholine, phosphatidylethanolamine, cholesterol and diphosphatidylglycerol. The parameters obtained support the qualitative conclusions of Toews et al. and provide quantitative estimates of the underlying processes, e.g., rates of vesicle and mitochondria translocation, rate constants for association and dissociation between vesicles, kinesin and microtubules, rates of deposition and rates of loss of each class of lipid from the nerve by leakage or via removal by the retrograde transport system. The analysis suggests that two classes of vesicles moving at different speeds may be involved in the transport of phosphatidylcholine and phosphatidylethanolamine. PMID- 1596522 TI - Bis(monoacylglycero)phosphate from PC12 cells, a phospholipid that can comigrate with phosphatidic acid: molecular species analysis by fast atom bombardment mass spectrometry. AB - Phospholipids from pheochromocytoma (PC12) cells were purified by one-dimensional thin-layer chromatography (TLC). Material corresponding in RF to phosphatidic acid (PA) was analyzed by fast atom bombardment mass spectrometry (FAB). The molecular ions of the major constituents corresponded in mass to phosphatidylglycerols (PG), which, however, have a lower RF value. Analysis of the mass spectra demonstrated that this material consists of bis(monoacylglycero)phosphates (BMP, lysobisphosphatidic acid), a structural isomers of PG. Linked scans of individual molecular ions indicate that BMP from PC12 cells is esterified almost exclusively with monounsaturated (16:1 and 18:1) and polyunsaturated (20:4 and 22:6) fatty acids. One of the two major molecular species contains two monounsaturated (18:1/18:1), while the other contains both a monounsaturated (18:1) and a polyunsaturated (22:6) fatty acid ester. FAB in combination with TLC is ideally suited for analysis of molecular species of phospholipids. PMID- 1596521 TI - Purification, characterization and substrate specificity of rabbit lung phospholipid transfer proteins. AB - Three phospholipid transfer proteins, namely proteins I, II and III, were purified from the rabbit lung cytosolic fraction. The molecular masses of phospholipid transfer proteins I, II and III are 32 kilodaltons (kDa), 22 kDa and 32 kDa, respectively; their isoelectric point values are 6.5, 7.0 and 6.8, respectively. Phospholipid transfer proteins I and III transferred phosphatidylcholine (PC) and phosphatidylinositol (PI) from donor unilamellar liposomes to acceptor multilamellar liposomes; protein II transferred PC but not PI. All the three phospholipid transfer proteins transferred phosphatidylethanolamine poorly and showed no tendency to transfer triolein. The transfer of [14C]PC from unilamellar liposomes to multilamellar liposomes facilitated by each protein was affected differently by the presence of acidic phospholipids in the PC unilamellar liposomes. In an equal molar ratio of acidic phospholipid and PC, phosphatidylglycerol (PG) reduced the activities of proteins I and III by 70% (P = 0.0004 and 0.0032, respectively) whereas PI and phosphatidylserine (PS) had an insignificant effect. In contrast, the protein II activity was stimulated 2-3-times more by either PG (P = 0.0024), PI (P = 0.0006) or PS (P = 0.0038). In addition, protein II transferred dioleoylPC (DOPC) about 2 times more effectively than dipalmitoylPC (DPPC) (P = 0.0002), whereas proteins I and III transferred DPPC 20-40% more effectively than DOPC but this was statistically insignificant. The markedly different substrate specificities of the three lung phospholipid transfer proteins suggest that these proteins may play an important role in sorting intracellular membrane phospholipids, possibly including lung surfactant phospholipids. PMID- 1596523 TI - Kinetic studies on androstenedione production in ovarian microsomes from immature rats. AB - Androstenedione formation from progesterone by P-450(17 alpha,lyase) was investigated in ovarian microsomes of immature rats treated with pregnant mare serum gonadotropin. Successive monooxygenase reactions in the formation of androstenedione without the intermediate leaving P-450(17 alpha,lyase) were demonstrated by a double-substrate double-label experiment using [14C]progesterone and 17 alpha-[3H]hydroxyprogesterone as substrates and also by specific reduction in the concentration of intermediate 17 alpha hydroxyprogesterone in the reaction medium by reaction of liposomal P-450C21. A detailed kinetic study on the reactions of P-450(17 alpha,lyase) in microsomes was conducted in the steady state. Kinetic parameters indicated the C17,C20-lyase reaction for 17 alpha-hydroxyprogesterone (Km = 80 nM) to be strongly inhibited by progesterone (Ki = 8 nM). In the presence of a high concentration of progesterone, as in the case of in vivo rat ovary, most androstenedione is concluded to be formed directly from progesterone by successive monooxygenase reactions catalyzed by P-450(17 alpha,lyase). 20 alpha-Dihydroprogesterone competitively inhibited the C17,C20-lyase reaction for 17 alpha hydroxyprogesterone with Ki = 23 nM, but had only slight effect on progesterone metabolism to androstenedione. 20 alpha-Dihydroprogesterone, thus, cannot be a regulator for androstenedione formation in rat ovary. PMID- 1596524 TI - "Purple" ulcers. PMID- 1596525 TI - AIDS Commission releases report. PMID- 1596526 TI - What is the purpose? PMID- 1596528 TI - Results of therapeutic bed monitoring: justification of ET nursing. AB - Therapeutic beds are used frequently at St. Vincent Medical Center, a 640-bed tertiary care hospital. The beds are designed to reduce body surface pressures for patients with potential for or actual pressure injury related to mechanical forces (pressure, friction, and/or shear). A monitoring system for therapeutic bed usage was initiated by the Enterostomal Therapy Department in March 1990 because of concerns about prolonged and sometimes unnecessary use of the beds. In this article, the monitoring system is described with the results after 1 year. PMID- 1596527 TI - Quality monitoring for maintenance of skin integrity. AB - In today's cost-conscious health care environment, the ET nurse is in a unique position to be instrumental in improving the quality of patient care. Continuous quality improvement in a cost-effective manner is the goal. Through collaborative efforts, the ET nurse and staff nurses have developed quality indicators for the maintenance of skin integrity in the belief that process, when provided effectively, will increase the probability of a desired outcome. Process indicators measure discrete nursing activities that contribute directly or indirectly to patient care. Closely linked process and outcome indicators were selected. Outcome refers to the effects of treatment on patients. Through evaluation, opportunities for improvement were identified and corrective action has been planned and will be implemented. PMID- 1596529 TI - Alteration of cell cycle kinetics by reducing agents in human peripheral blood lymphocytes from adult and senescent donors. AB - For improving cell proliferation reducing agents are routinely used as medium supplements in murine cell cultures, however, they are rarely used for human peripheral blood lymphocytes (PBLs). Data on changes in cell kinetics induced by reducing agents are not available. Here cell kinetic alterations induced by reducing agents in human lymphocytes are revealed by applying flow cytometric BrdUrd/Hoechst cell cycle analysis and by using the exit kinetic model of Smith and Martin. Applying alpha-thioglycerol (a-TG) as a model compound it was shown that the major cell kinetic effect is a shortening of the mean duration of the G0/G1 phase. The minimum G0/G1 phase duration and the percentage of the non cycling G0/G1 cell fraction decrease only slightly. Moreover, a lower number of PBL's are arrested in the G2/M phase of the 1st cell cycle. The durations of the S and G2/M phase in the 1st and G1 phase in the 2nd cycle are not affected. These cell kinetic effects are identical for lymphocytes from both adult and senescent donors. The supplementation of the cell cultures with recombinant IL-2 did not induce similar cell kinetic alterations compared with a-TG. This indicates that the variation of the cell cycle progression factor IL-2 is not solely responsible for improvement of the cell activation process in the G0/G1 phase. PMID- 1596530 TI - A cytokinetic approach to determine the range of O2-dependence of pyrimidine(deoxy)nucleotide biosynthesis relevant for cell proliferation. AB - In vitro cultured Ehrlich ascites tumour (EAT) cells were used because of the ease of their manipulation under different levels of hypoxia. They were used to clarify further the complex mechanism of oxygen-dependent cell proliferation. On reducing the oxygen concentration from 20% to lower levels (1-7%) an increase in the length of the population doubling time with concomitant reductions in protein, RNA and DNA content of cultures were observed. The incorporation of [14C]HCO3- into the RNA fraction of cells by de novo biosynthesis of uridine monophosphate (UMP) was reduced proportionally to the microenvironmental O2 tension. Uptake of this labelled precursor by cells in the presence of N phosphonoacetyl-L-aspartate was found to be similarly inhibited. To correlate the reduction of cell growth under hypoxia with the functional pyrimidine supply, hypoxic cells were cultured in the presence of a balanced mixture of deoxynucleosides and/or uridine (100 microM deoxycytidine, 10 microM deoxyadenosine, 10 microM deoxyguanosine, 100 microM uridine). Above 3% O2 in the protective atmosphere, no improvement of growth parameters by the exogenous pyrimidinenucleotide precursors was obtained, whereas these compounds had a positive influence below this level. The increase in cell number was raised to about 60% of that of control cultures (20% O2) irrespective of the oxygen tension. In addition, when above 3% O2 the incorporation of HCO3- into RNA was comparable to that of controls, indicating that the pyrimidine de novo pathway is not a limiting factor in RNA biosynthesis. In conclusion, whereas at suboptimal O2 levels (5-7%) no correlation between pyrimidine metabolism and reduction of proliferation rate appears to exist, at low O2 concentrations (less than 3%) the rate of orotate/UMP production seems to be an important factor in the growth cessation of EAT cells; at critical O2 tensions (less than 1%) the lack of pyrimidine-deoxynucleosides substantially reduces cell cycle progression. PMID- 1596531 TI - Protein synthesis inhibitors, like growth factors, may render resting 3T3 cells competent for DNA synthesis: a radioautographic and cell fusion study. AB - Serum-deprived (0.1-0.2%) resting NIH 3T3 mouse fibroblasts pre-incubated with cycloheximide (7.5 micrograms/ml), or puromycin (10 micrograms/ml), were fused with stimulated cells taken 10 h after changing the medium to one containing 10% serum, and DNA synthesis was investigated in the nuclei of monokaryons, homodikaryons and heterodikaryons using radioautography with the double-labelling technique. Pre-incubation of resting cells with inhibitors of protein synthesis for 1-4 h abolished their ability to suppress DNA synthesis in stimulated nuclei in heterokaryons. Three hours after the removal of cycloheximide from the medium, the resting cells acquired once again the inhibitory capacity for entry of stimulated nuclei into the S period. This inhibitory influence disappeared also in the case of post-fusion cycloheximide application as well as following an 8-12 h pre-treatment of resting cells with actinomycin D (1 microgram/ml) prior to fusion. Pre-incubation of resting cells for 12 h with PDGF (1 u/ml-1) followed by an 8-48 h incubation in serum-free medium stimulated the onset of DNA synthesis. A brief exposure (45 min) of resting cells to cycloheximide (7.5 micrograms/ml), or puromycin (7.5 micrograms/ml), exerted a similar effect, inducing by itself the entry of cells into the S period. The results support the assumption that acquirement, by resting cells, of competence for DNA replication includes as a necessary step the down-regulation of intracellular growth inhibitors whose formation depends on protein synthesis. PMID- 1596532 TI - The multi-site tumour transplantation model for human endometrial carcinoma: a statistical evaluation. AB - We studied the effect of multi-site tumour transplantation on tumour growth by implanting varying numbers of EnCa 101 human endometrial tumours in athymic mice. One treatment group received a single tumour per mouse, another group received two tumours per mouse and a third group received four tumours per mouse. Tumour growth was sustained in all animals by implantation of oestradiol-17 beta pellets. We observed positive correlation between tumours within the same mouse, which implies that individual tumours are not statistically independent. The correlation is sufficiently large that failure to account for it in statistical design and analysis could result in studies with insufficient power and in spurious assertions of significance. Regression modelling of tumour growth curves showed that mean tumour volume per animal is not affected by the number of tumours growing on the animal; that is, the data are consistent with the null hypothesis that mean tumour volume is the same regardless of the number of tumours present. Our results therefore suggest that the use of multiple tumours per animal can increase the precision of experiments without loss of validity and at relatively little cost. However, correct and efficient analysis of the data so obtained requires more sophisticated techniques than those--such as fixed-effects analysis of variance and the two sample t-test--that assume independence of tumours. PMID- 1596533 TI - The serum response element and an AP-1/ATF sequence immediately downstream co operate in the regulation of c-fos transcription. AB - Transcription of the c-fos gene is activated in response to a wide variety of extracellular stimuli and several cis-acting transcriptional control elements have been characterized. One of these elements is called the serum response element (SRE) and here we investigate an interaction between this element and an AP-1/ATF-like sequence immediately downstream from the SRE. In growing cells these sequences activate transcription in an additive fashion whereas in quiescent cells they co-operate to repress transcription. This co-operation is disrupted upon separation of the elements which also alters the response of the elements to serum or 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation of quiescent cells. This separation also results in an increase of transcription in growing cells. A consensus AP-1 DNA-binding site can substitute for the AP-1/ATF like sequence present in the c-fos promoter to activate transcription in an additive fashion with the SRE in growing cells, and co-operate in repression in quiescent cells. These observations show that any interaction that may be occurring between proteins binding to these elements results in a different pattern of transcriptional control in growing and quiescent cells. Alternatively, different proteins (or modified proteins) may complex with these sequences in the two different states of cell growth. PMID- 1596534 TI - Clonal heterogeneity in specific growth rate of Saccharomyces cerevisiae cells. AB - The cell volume increase in individual clones of cells of the yeast Saccharomyces cerevisiae has been measured using time lapse cinematography in populations showing steady state balanced exponential growth. There were significant differences in clonal specific growth rates within the population in each of 10 experiments using different strains on different media supporting different growth rates. The results suggest that specific growth rates of cells which are either genetically identical or very closely related can be different and this difference can be propagated over at least three generations. Since the proliferation rate in yeast is determined by growth rate, these observed differences provide an additional source of cell cycle variability for yeast cells that has not been considered before. The implications for the theoretical analysis of cell cycle kinetics are examined. PMID- 1596535 TI - Interferon affects cell growth progression by modulating DNA polymerases activity. AB - A multiparametric analysis of the effects of human recombinant interferon alpha type A on Daudi cells involving flow cytometry and in vitro analysis of alpha and beta DNA polymerase activities has been performed. Results have disclosed (within 60 min of interferon treatment) a decrease of alpha polymerase driven DNA synthesis persisting to at least 24 h, while beta polymerase was poorly affected. Moreover, after 24 h of interferon treatment, a reduction of BrdUrd incorporation per cell, assessed by flow cytometry, was observed suggesting that DNA synthesis in S phase cells is almost completely abolished. The analysis of the effect of interferon on the distribution of cell cycle phases indicated that the G1/S transition is not inhibited by the treatment. These results support the hypothesis that interferon generates a transient initiating signal which quickly reaches the nucleus and produces a rapid inhibition of alpha polymerase activity, leading finally to the slowing of cell cycle progression. PMID- 1596536 TI - Kinetics of the calcium induced stratification of human keratinocytes in vitro. AB - In a low concentration of calcium (0.1 mM), keratinocytes form a monolayer with about 30% of cells synthesizing involucrin. After addition of calcium to the culture medium to a concentration of 1.2 mM, the monolayer stratifies within 24 h, with a preferential migration of involucrin positive keratinocytes. In the present study, we tried to determine if keratinocytes control the decision to migrate at a distinct cell cycle point. A percentage labelled mitosis (PLM) curve was constructed for keratinocytes grown in low calcium medium and values for the length of the cell cycle (47 h), S phase duration (11 h) and G2+M period (6 h), were obtained. Monolayer cultures at 80% confluence were switched to high calcium concentration at various times (from 0 to 48 h), after pulse labelling with [3H] thymidine. Based on the PLM data, the behaviour of cells known to be in S, G1 and G2 at the time of the migration stimulus were followed. No significant difference in the percentage of labelled suprabasal cells was found for any point of the cell cycle. For cells submitting to stratification, in S phase involucrin staining showed that about 60% of the [3H]-thymidine labelled cells were also involucrin negative. These results indicate that upward migration of keratinocytes in cultured epithelium can be triggered at all points in the cell cycle with equal probability and is not restricted to those cells that already contained involucrin. PMID- 1596537 TI - Spermatogonial apoptosis has three morphologically recognizable phases and shows no circadian rhythm during normal spermatogenesis in the rat. AB - In this study we examined the possibility that regular or circadian fluctuations occur in the frequency of spontaneous spermatogonial apoptosis. Apoptosis of A2, A3 and A4 type spermatogonia occurring spontaneously in the normal rat testis was studied by light and electron microscopy. Normal and apoptotic A3 spermatogonia were quantified in 36 animals killed at two-hourly intervals over a 24 h period. Three sequential phases of spermatogonial apoptosis were defined and quantified separately: (i) an early phase in which cells showed margination of nuclear chromatin, (ii) an intermediate phase in which phagocytosed apoptotic bodies were partly degraded and (iii) a late phase in which only debris of degraded apoptotic bodies was evident. Groups of spermatogonia linked by intercellular bridges underwent apoptosis synchronously. Normal and apoptotic A3 spermatogonia occurred at a mean frequency of 33.4 and 9.6 per 10 seminiferous tubule profiles respectively; there was a large variation in these frequencies between animals, but no peaks or circadian periodicity were detected. Progressive degradation of apoptotic bodies was evident, the average ratios of intermediate and late bodies to early bodies being 1.5 and 3.5, respectively. Absence of a circadian rhythm in these data does not exclude the possibility that initiation of apoptosis in susceptible spermatogonial clones is synchronous, and that affected clones undergo lag periods of differing duration before expressing morphological apoptosis. PMID- 1596538 TI - G1 shortening following unbalanced growth: a specific v. nonspecific effect. AB - The synthesis and abundance of proteins were examined in synchronous populations of HeLa cells under conditions in which the lengthening of S phase, by inhibiting DNA synthesis, resulted in shortening of G1 in the subsequent generation. Mitotically collected cells were resynchronized by incubation with 3 microM aphidicolin from 3 to 12 h after mitotic selection; they were blocked again at various times thereafter to induce unbalanced growth. Cells were labelled with [35S]-methionine before and after release from the block to study the changes in protein synthesis. Triton X-100 soluble and insoluble proteins were analysed by 7 15% gradient SDS-PAGE, and radioactivity incorporation was quantified by liquid scintillation counting. The degree of G1 shortening correlated with S phase position, increasing gradually from early S and reaching maximum when cells were blocked half-way through S phase. Synthesis of proteins of 120, 66, and 51 kDa was stimulated, and synthesis of a new protein of 57kDa was observed, in cells in which DNA synthesis had been blocked in mid-S. These proteins also showed increased accumulation. These results suggest that the shortening of G1, induced by the prior arrest of cell-cycle progression, is associated with synthesis of specific proteins rather than the non-specific accumulation of cellular proteins through unbalanced growth. PMID- 1596539 TI - [Indications for the preoperative thoracic x-ray]. PMID- 1596540 TI - [Pericoxal fat stripes and the capsule of the hip joint. The anatomical radiological correlations]. AB - The capsule of the hip joint can always be demonstrated on antero-posterior radiographs provided two conditions are met: 1. the so-called gluteus minimus fat stripe is shown and 2. the exposure is made in maximal external rotation which can be either active or, better still, passive. Under these conditions the joint capsule appears as a soft tissue band stretched between the margin ot the acetabulum and the upper end of the greater trochanter. Effusions or oedemas of the hip joint cause lateral displacement of the gluteus minimus fat stripe. Anatomical and radiological comparisons, including computed tomography, confirm that the joint capsule of the hip can be demonstrated in this way. PMID- 1596541 TI - [Pre- and postoperative NMR tomographic studies in avascular femur head necrosis]. AB - 46 patients with avascular necrosis of the femoral head were examined by T2- and T1-weighted MR before and after infusion of Gd-DTPA. Both sides were involved in 12 cases. The classification was done according to Ficat. In early stages and in postoperative studies a correlation of signal intensity after infusion of Gd-DTPA and clinical symptoms was found. Hyperintensity of the avascular area or of the implanted material was assumed to be vascularised or vital components in 4 cases of Ficat I and in 15 postoperative studies. Contrariwise, we found in 5 patients with severe postoperative symptoms, low signal intensity areas due to avascular regions. PMID- 1596542 TI - [Pelvic roentgenometry of the third kind: age- and sex-related measurement results in adulthood]. AB - Normal values in adults for the hip joint (3.5-6 mm), the sacro-iliac joint (1 3.5 mm) and the symphysis (up to 7.5 mm) were obtained by measurements of a.p. views of the pelvis. Contrary to the literature there was no sex difference as regards the CCD. The roentgenometric features of the female and male pelvis depend on the pubic angle, the transverse diameter of the pelvic inlet and the sulcus paraglenoidalis. In females there are age-related changes consisting of a reduction of the pubic angle, increasing height of the symphysis components of the pubis and an increase in the transverse diameter of the pelvis. In the male, age changes consist of an increase of the symphysis component of the pubis and the transverse diameter of the pelvis. PMID- 1596543 TI - [Do the obstetrically relevant bony pelvic measurements change? A retrospective analysis of computed tomographic pelvic x-rays]. AB - The important dimensions of pelvimetry were evaluated from 467 CT studies of the pelvis by trigonometric deduction. The age of the women was between 18 and 88 years. In addition to the diameters, which are routinely used for pelvimetry, transverse and sagittal diameters, pelvic angles and areas of pelvic planes were calculated. On condition that the pelvic dimensions do not depend on age the parameters can be regarded as representative of sexual maturity. 5 parameters showed highly significant and 7 parameters showed significant differences between the age-classes 1901-1920 and 1950-1971. An increase of pelvic dimensions (1950 1971) was found at the planes of the pelvic inlet and outlet in contrast to the dimensions of the pelvic center. The results confirm the importance of the bispinous diameter for pelvimetry as well as the demand for a revision of the standard values of the first half of the century. PMID- 1596545 TI - [Computed tomography in the diagnosis of recurrent herniated disks following prior lumbar intervertebral disk operations]. AB - 20 patients with recurrent symptoms following operations for disc prolapse and resistant to treatment were studied by CT, using plain and enhanced images. The results have been analysed. In 10 patients a recurrence of disc prolapse was diagnosed, and this was confirmed surgically in 8 cases. In 2 patients there was epidural scarring. The findings indicate that differential diagnosis between scarring and recurring prolapse can be accurately made by this technique. PMID- 1596544 TI - [Stereolithographic model construction based on 3-dimensional reconstructed CT sectional image sequences]. AB - Techniques for 3D reconstruction of medical objects and production of models by CAM have been markedly improved. Milling tools have limited abilities to reproduce complex anatomical structures. Even if 5-axis milling systems are used, the problem of collisions between tool and object is not yet under control. An alternative is offered here by stereolithography. We performed a computed tomography (Somatom DRH, Siemens/Erlangen) of a child with extensive maxillary bone defect after surgical treatment of a congenital tumour. The bone defect was covered by an alloplastic implant. 3D reconstructions were performed by the aid of a conventional personal computer. Generated 3D volume data sets were transferred to a stereolithography system (3D Systems GmbH, Darmstadt/FRG). The produced model revealed high accuracy of the anatomical structures. Intraoperatively, the alloplastic prosthesis was removed and the shape of the new implant could be designed using the stereolithographic model. PMID- 1596546 TI - [The value of digital subtraction sialography compared to conventional sialography, salivary gland sonography and surgical findings]. AB - In a prospective study DSA sialography, conventional sialography (100mm technique) and sonography of the salivary glands were performed in 124 patients. The results of imaging could be correlated with those of operation and/or histology in 70 patients. Performing sialography in only one projection DSA sialography is superior to the conventional technique. The results of DSA are equivalent to those of conventional sialography in more than one projection. DSA sialography is the method of choice demonstrating salivary calculi, whereas sonography is superior to DSA sialography in the detection of tumors. In the diagnosis of chronic inflammation of the salivary glands DSA is slightly superior to the other imaging modalities. PMID- 1596548 TI - [The value of barium double-contrast study in the aftercare of gastrectomy patients (Roux-Y)]. AB - We evaluated 32 patients who had undergone jejuno-oesophagostomy for gastric carcinoma. Double contrast radiography was performed 3 to 36 months after gastrectomy, 3 to 14 days prior to routine endoscopy. Endoscopy is superior to double contrast radiography in detecting tumour recurrence, particularly in small tumours, due to the possibility of biopsy. Double contrast radiography is excellent in demonstrating the afferent loop. We found a high number of jejuno oesophageal reflux and very different small intestine transit times without correlation to clinical signs and symptoms. PMID- 1596547 TI - [Intestinal contrasting in abdominal computed tomography]. AB - In 56 patients undergoing abdominal CT the gastrointestinal tract was defined by negative contrast instead of the conventional positive contrast from an iodine containing contrast medium. The contrast material was a 2 1/2% mannitol solution and was used for filling the rectum. Filling of the gastrointestinal tract was of similar quality to that obtained with positive contrast media. The number of artifacts due to high contrast boundaries was slightly greater with the negative contrast than it would have been with positive contrast. Differentiation of the gastrointestinal tract from other abdominal organs was equally good for both methods. The negative contrast method was poor in diagnosing cystic tumours but proved much better than positive contrast for evaluating the wall of the gastrointestinal tract. PMID- 1596549 TI - [The computed tomographic staging of gastrointestinal tumors]. AB - During a period of six years 131 patients had CT for gastrointestinal tumours or inflammatory bowel disease; the results were analysed retrospectively according to standard criteria. The preoperative CT appearances were compared with the surgical and histological findings. Confirmation of the diagnosis was obtained at surgery and from pathological studies carried out within six weeks of the CT. There were 93 malignant and 8 benign tumours and 30 inflammatory lesions. The reliability of CT for determining tumour extent and the presence of metastases can be improved by standardising the method of examination. Altogether a sensitivity of 75-85%, a specificity of 89-96% and an accuracy of 83-86% was obtained, depending on the anatomical lesion. Correct findings of all three staging parameters T, N and M for carcinomas was, however, obtained in only 56%. Differentiation between malignant and benign tumours and from inflammatory lesions was possible in the presence of specific CT patterns. PMID- 1596550 TI - [Manganese-DPDP in the MR tomography of malignant liver tumors. The initial results with a new hepatobiliary contrast agent]. AB - The new hepatobiliary contrast agent Mangan-DPDP, unlike extracellular Gd-DTPA, leads to a constant increase in signal intensity of normal liver tissue in MR imaging of the liver which lasts at least for 30 minutes. In 19 patients with malignant liver tumors there was no difference in the contrast between tumor and liver when using a dose of 5 or 10 mumol/kg. Contrast enhanced T1-w SE- and T1-w GE sequences show a significant increase in tumor/liver contrast compared with T1 weighted unenhanced sequences. This increase was also significant when compared with T2-w SE sequences. In 16% additional focal lesions were detected on the enhanced scan. PMID- 1596551 TI - [NMR tomography of the liver with the new contrast agent Gd-BOPTA. The results of an in-vivo phase-I test]. AB - A phase 1 study on 8 normals has been carried out to determine the effectiveness and safety during MRI of a new hepatobiliary contrast medium Gd-BOPTA for causing enhancement of the upper abdominal organs. Gradient echo sequences (flash), T1 and T2-weighted spin echo sequences and turbo-flash sequences were used. The contrast medium was given as a single infusion in various concentrations (0.005, 0.05, 0.1, and 0.2 mmol/kg body weight). Optimal contrast of liver parenchyma was obtained with a dose of 0.05-0.1 mmol/kg body weight, resulting in contrast increase of 149.1% during gradient echo sequences and 107.8% during T1 spin echo sequences. In general, the increased contrast lasted for about two hours. Because of the biliary and renal excretion there was an enormous increase in signal intensity of the bile ducts and a significant increase in the kidneys and ureters. The results of the first in-vivo trial of Gd-BOPTA encourages the performance of further clinical studies of this new hepatobiliary contrast medium. PMID- 1596552 TI - Enhancement of the pancreas after single bolus injection combined with spiral scanning. A comparative study with conventional incremental scanning after biphasic contrast injection. AB - The combination of a rapid single bolus injection (72 ml of a 60% concentrated iodinated contrast medium) with spiral scanning versus dynamic sequential scanning with a conventional biphasic bolus injection (150 ml of 60% concentrated iodinated contrast medium) is compared. 60 patients with normal pancreatic morphology were included in this study. 30 patients were examined with dynamic sequential scanning (cycle times of 5 seconds) during a biphasic bolus injection, 30 patients were examined with spiral scanning (cycle times of 1 second) after a single uniphasic bolus injection. For both scanning techniques, mean attenuation values of the pancreas were measured before and at different time intervals after contrast injection. The difference in attenuation values of the pancreas before and after contrast injection reflects the level of contrast enhancement in both methods. The level of contrast enhancement of the pancreas after bolus injection was not statistically significantly different in spiral scanning versus in dynamic sequential scanning. In comparison with conventional scanning, spiral scanning allows to reduce the injected dose of contrast by 50% without compromising the contrast resolution. PMID- 1596553 TI - [Experimental studies on magnetic resonance tomographic and magnetic resonance angiographic imaging of poststenotic flow patterns]. AB - A phantom has been developed, which permits the perfusion of defined stenosis with variable flow rates. The post-stenotic flow patterns were imaged by means of conventional MRI sequences and special angiographic sequences using a 1.5 total body scanner (Gyroscan S15, Philips). For conventional MRI images, spin-echo sequences (TR 500 ms, TE 27 ms with reconstruction of the magnitude and phase images) and gradient-echo-sequences (TR 60 ms, TE 27 ms, flip angle 15 degrees with reconstruction of the magnitude images) were used. For MR angiography 2D inflow (multiple-single-slice-technique, TR 40 ms, TE 14 ms, flip angle 60 degrees) and flow-adjusted-gradient-sequences (TR 24 ms, TE 10 ms, flip angle 60 degrees) were performed. In addition to an analysis of the appearances, the length of the changed signal intensity beyond the stenosis was evaluated. For constant flow rates it increases with the severity of the stenosis. For a constant stenosis the length of the post-stenotic signal change alters with flow rate. The changes also depend on the direction of flow and the gradients of the chosen sequences. The comparison of magnitude and phase images allows the discrimination between turbulent and non-turbulent flow. It therefore appears possible to estimate the severity of arteriosclerotic occlusive disease by means of MRI in the future. PMID- 1596554 TI - [The detailed imaging of vessels in MR angiography via projections from irregularly restricted data sets]. AB - A new method for postprocessing of three dimensional magnetic resonance angiography data sets is described. Two operations are performed with the data set prior to maximum intensity projection. First, an irregular part of interest is marked interactively within the data set. By restricting the projection algorithm to this region, a disturbing overlay by vessels of other regions is avoided. Secondly, a three dimensional interpolation of the original data set is performed. While the spatial resolution of vessel representation is unchanged, the quality of the maximum intensity projection is improved significantly. The diagnostic value of this method is demonstrated by visualisation of a carotid aneurysm and of the deep and superficial cerebral veins. PMID- 1596555 TI - [Computed tomographic studies on density kinetics after the bolus injection and infusion of perfluorooctylbromide (PFOB). Animal experimental studies]. AB - We investigated the enhancement of the liver, the spleen, and of induced abscesses and the abdominal vessels after administration of 3 g/kg bodyweight. Perfluorooctylbromide (PFOB) in an animal model. Twenty-one rabbits each received the contrast medium as bolus injection and as slow infusion over half an hour. CT was performed between 2 and 48 hours after contrast medium application. Peak enhancement of the liver, the spleen and the liver abscess membrane was found between 24 and 48 hours after PFOB administration, independently of the application mode. Peak enhancement of the abdominal aorta and the IVC was observed within two hours after bolus injection. In this rabbit model PFOB permits best delineation of the vessels after bolus injection within the first two hours, while CT imaging of the liver, the spleen and the liver abscess membrane is best between 24 and 48 hours after contrast medium application, independent of the injection velocity. PMID- 1596557 TI - Calcaneal avulsion: a frequent traumatic foot lesion. PMID- 1596558 TI - [The cholesterol granuloma of the frontal sinus. Its radiological morphology and differential diagnostic aspects]. PMID- 1596556 TI - [A holding device for functional patellar tangential x-rays during quadriceps contraction]. PMID- 1596559 TI - [Bilateral chondrosarcomas in the cerebellopontine angle in Maffucci's syndrome]. PMID- 1596560 TI - [Cerebral B-cell lymphoma with the neuroradiological picture of multifocal leukoencephalopathy]. PMID- 1596561 TI - Interleukin-5, eosinophils, and disease. PMID- 1596562 TI - Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial. AB - Until recently, cryoprecipitate has been the treatment of choice in patients with severe von Willebrand disease (vWD) because it can transiently correct low plasma levels of factor VIII coagulant activity (FVIII:C) and shorten or normalize the prolonged bleeding time (BT), the two laboratory hallmarks of the disease. However, cryoprecipitate may still transmit blood-borne viruses, whereas the development of virucidal methods have rendered plasma concentrates containing FVIII:C and von Willebrand factor (vWF) safer. To establish their potential usefulness in the treatment of vWD, we compared the effect of four virus inactivated concentrates on FVII:C and vWF plasma levels and the BT (template method) in 10 patients with severe vWD using a crossover randomized design. The concentrates were an intermediate-purity, pasteurized FVIII-vWF concentrate; an intermediate-purity, dry-heated FVIII-vWF concentrate; a solvent/detergent treated vWF concentrate, containing little FVIII; and a high-purity solvent/detergent-treated FVIII-vWF concentrate. All concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed after the vWF concentrate. The effect of concentrates on the BT, however, was less uniform and satisfactory. The pasteurized FVIII-vWF concentrate transiently corrected, completely or partially, the BT in 8 of 10 patients, the dry-heated and solvent/detergent FVIII/vWF concentrates in five, whereas in no patient did the vWF concentrate correct the BT according to the criteria used in this study. These effects on the BT were not related to the plasma levels of ristocetin cofactor activity-attained postinfusion (100 U/dL or more in the majority of patients) or to the multimeric structure of vWF in concentrates (defective in larger multimers in all cases). In conclusion, even though virus-inactivated concentrates can be used to increase FVIII:C levels in patients with severe vWD, none of the concentrates studied by us consistently normalizes the BT in a sustained fashion. PMID- 1596563 TI - "Stem cell" origin of the hematopoietic defect in dyskeratosis congenita. AB - We have used the long-term bone marrow culture (LTBMC) system to analyze hematopoiesis in three patients with dyskeratosis congenita (DC), two of whom had aplastic anemia, and the third had a normal blood count (apart from mild macrocytosis) and normal BM cellularity. Hematopoiesis was severely defective in all three patients, as measured by a low incidence of colony-forming cells and a low level of hematopoiesis in LTBMC. The function of the marrow stroma was normal in its ability to support the growth of hematopoietic progenitors from normal marrows seeded onto them in all three cases, but the generation of hematopoietic progenitors from patients marrow cells inoculated onto normal stromas was reduced, thus suggesting the defect to be of stem cell origin. The parents and unaffected brother of one of the families have also been studied in LTBMC and all showed normal hematopoietic and stromal cell function. From this study we speculate that there are some similarities between DC and the defect in the W/Wv mouse. PMID- 1596564 TI - Interleukin-4 inhibits interleukin-1 alpha-induced granulocyte-macrophage colony stimulating factor gene expression in a murine B-lymphocyte cell line via downregulation of RNA precursor. AB - Interleukin-4 (IL-4) regulates the growth of B cells. When combined with colony stimulating factors (CSFs) and selected cytokines, IL-4 has a synergistic effect on the clonal growth of bone marrow cells. Recently, we have shown that IL-1 alpha and lipopolysaccharide induce expression of the granulocyte-macrophage CSF (GM-CSF) gene in murine B-cell lines. In the present study, we show that IL-4 inhibits the production of GM-CSF in the IL-1 alpha-stimulated murine B-cell line M12.4.1. IL-4 did not change the transcription rate of the GM-CSF gene, and caused only a slight decrease in cytoplasmic GM-CSF messenger RNA (mRNA) half life in cells treated with IL-1 alpha. PCR analysis of nuclear RNA with probes specific for GM-CSF intron sequences suggests that IL-1 alpha enhances accumulation of nuclear precursor RNA and that decreased GM-CSF expression after IL-4 treatment is mainly due to intranuclear destabilization of the primary transcript. Under the same experimental conditions, IL-4 did not affect expression of the IL-4 receptor mRNA and did increase the mRNA concentration of the low-affinity receptor for IgE (Fc epsilon RII). These data suggest that the suppressive effect of IL-4 is specific for GM-CSF mRNA expression, and thus provide evidence for an additional role of IL-4 in the regulation of GM-CSF expression in B cells. PMID- 1596566 TI - Hyperdiploid (47-50) acute lymphoblastic leukemia in children. AB - Among ploidy groups in childhood acute lymphoblastic leukemia (ALL), hyperdiploidy 47 to 50 is perhaps the least well known. From December 1979 to December 1990, we successfully studied banded karyotypes in 598 cases of newly diagnosed ALL, of which 86 (14.4%) had modal chromosome numbers of 47 to 50. In this group, the most frequently acquired numerical abnormalities were +21 (n = 34), +X (18), +8 (8), and +10 (7). The chromosomal regions most often affected by structural abnormalities were 1q (n = 13), 6q (12), 12p (18), and 19p (9). Analysis of event-free survival (EFS) for Studies X and XI among patients with hyperdiploid (47 to 50) ALL showed no significant differences in outcome according to the presence (n = 36) or absence (n = 35) of chromosomal translocations (P = .81) or the gain of specific chromosomes (P = .40). Patients with hyperdiploid (47 to 50) ALL treated in a contemporary program of multiagent chemotherapy had a significantly better outcome than did those in an earlier study using less intensive therapy (4-year EFS = 75% [95% confidence interval, 55% to 86%] v 41% [22% to 59%]; P = .006 by the logrank test). Our findings indicate that the adverse prognosis previously attributed to hyperdiploidy 47 to 50 improves significantly with more effective chemotherapy. PMID- 1596565 TI - Expression of tissue factor pathway inhibitor by cultured endothelial cells in response to inflammatory mediators. AB - We recently proposed that endothelium may represent the primary physiologic site of synthesis of the tissue factor pathway inhibitor (TFPI). In support of this conclusion, we have now found that the poly(A)+ RNAs obtained from rabbit and bovine lung tissues contain abundant amounts of TFPI messenger RNAs (mRNAs), whereas the poly(A)+ RNAs obtained from the liver of these animals contain less than 5% of that found in the lung tissues. Because inflammatory mediators are known to upregulate tissue factor (TF) expression by the endothelium, we have examined the effect of these agents on the TFPI expression by the cultured endothelial cells. When cultured human umbilical vein endothelial cells were stimulated (in 10% fetal bovine serum) with phorbol myristate acetate (PMA), endotoxin, interleukin-1, or tumor necrosis factor-alpha, the TF mRNA increased approximately 7- to 10-fold within 2 to 4 hours. Unstimulated cells constitutively expressed TFPI mRNA and its levels either did not change or increased slightly (up to 1.5-fold) upon stimulation with these inflammatory agents. TF mRNA abruptly declined to a negligible level and the TFPI mRNA returned essentially to the basal level at approximately 24 hours. The membrane bound TF clotting activity of induced cells peaked between 4 and 8 hours, and finally declined. The cumulative TFPI activity secreted into the media was either unchanged or slightly higher in the induced cell cultures as compared with that present in the noninduced cultures. Endothelial cells were also cultured in 10% heat-inactivated human serum derived from plasma or whole blood. TFPI secreted into the media containing whole blood serum was consistently higher (approximately 1.5-fold at 8 hours) than that secreted into the media supplemented with serum obtained from plasma lacking the formed elements; these cells also expressed similarly increased levels of TFPI mRNA. Moreover, PMA stimulated cells cultured in whole blood serum expressed modestly increased levels of TFPI mRNA (approximately 1.5-fold); supernatants from these cells also contained similarly increased TFPI activity. Cumulatively, our data indicate that, unlike thrombomodulin and fibrinolytic enzymes synthesized by the endothelial cells, TFPI synthesis is not downregulated and may be slightly upregulated during an inflammatory response. Inspection of the 5' flanking region of the TFPI gene showed a conserved GATA-binding motif located approximately 400 bp upstream of the proposed transcription initiation site(s). This motif by binding to the GATA-2 transcriptional factor may keep the endothelium in an 'on' state for constitutive expression of TFPI.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1596567 TI - Comparative cellular pharmacology of daunorubicin and idarubicin in human multidrug-resistant leukemia cells. AB - We examined the effect of daunorubicin (DNR), the new anthracycline derivative idarubicin (IDR), and verapamil on two leukemia cell lines that displayed the multidrug resistant (MDR) phenotype and used laser flow cytometry to quantitate intracellular anthracycline content. The vinblastine-resistant human lymphoblastic leukemia cell line CEM-VBL demonstrated minimal DNR uptake; simultaneous incubation with verapamil and DNR increased intracellular DNR uptake fourfold. IDR uptake was 10 times more rapid in these cells and simultaneous incubation with IDR and verapamil resulted in only a 1.2-fold increase of intracellular IDR. Similar results were observed in the vincristine-resistant human myeloid leukemia cell line HL-60/RV+. Intracellular retention of DNR and IDR was also measured in each cell line. In CEM-BVL cells, 38% of the original DNR concentration remained after a 2-hour resuspension in fresh medium compared with 71% of the original IDR concentration. In HL-60/RV+ cells, 36% of the DNR concentration remained compared with 51% of the IDR concentration. After incubation of CEM-VBL and HL-60/RV+ cells with DNR for 1 hour followed by resuspension in fresh medium plus verapamil, intracellular DNA retention increased 5- and 5.2-fold, respectively. However, incubation of these cells for 1 hour with IDR followed by resuspension in fresh medium plus verapamil resulted in only a 1.6- and 2.4-fold increase in intracellular IDR retention. Lastly, clonogenic experiments were performed to correlate intracellular anthracycline content with cytotoxicity. DNR alone had a minimal effect on the clonogenic growth of CEM-VBL cells, whereas the combination of DNR plus verapamil resulted in approximately 80% growth inhibition. However, incubation of these cells with IDR alone resulted in greater than 95% growth inhibition. These results suggest that IDR may be more effective than DNR in leukemia cells that display the MDR phenotype. PMID- 1596568 TI - In vitro culture of common acute lymphoblastic leukemia blasts: effects of interleukin-3, interleukin-7, and accessory cells. AB - We investigated the effects of interleukin-3 (IL-3), IL-7, IL-1, and IL-6, of irradiated bone marrow-derived fibroblasts (Fb) and of in vitro matured peripheral blood macrophages (M phi), on the survival, proliferation, and maturation of purified blasts from nine common acute lymphoblastic leukemias (cALLs) in 7-day suspension culture. Exposure to IL-3, IL-7, IL-1, and IL-6 resulted in a mean 2.8-, 1.5-, 1.4-, and 1.6-fold stimulation of 3H-thymidine (3H TdR) incorporation, respectively. Cocultures of cALL blasts with irradiated M phi, either allowing direct cell-cell contact or preventing it by membrane filters, or with irradiated Fb, resulted in a mean 31.7-, 4.1-, and 11.2-fold increase of 3H-TdR incorporation, respectively. Southern blot analysis of immunoglobulin and T-cell receptor (TCR) gene rearrangements before and after culture indicated exclusive proliferation of the leukemic clone in three of eight samples, whereas additional generation of nonleukemic cells was found in five samples. Polyclonal growth pattern corresponded to the detection of heterogeneous cell populations using FACS analysis. Survival of cALL blasts as defined by the detection of cells coexpressing both CD10 and CD19 after culture was supported by accessory cells in five of eight samples. No evidence of induced lymphoid maturation was found under any culture condition. Our data demonstrate supportive effects of stromal cells on cALL growth, which cannot be replaced by IL-3 or IL 7. PMID- 1596569 TI - Preferential synthesis of the 78-Kd glucose-regulated protein in glucocorticoid treated S49 mouse lymphoma cells. AB - To investigate the mechanism of glucocorticoid-induced lymphocytolysis, we used two-dimensional gel electrophoresis to analyze the effect of dexamethasone on the synthesis of individual proteins in S49 mouse lymphoma cells. We found that synthesis of a 78-Kd protein is preferentially maintained following dexamethasone treatment, at a time when the synthesis of most other cellular proteins is decreased. Synthesis of this protein could also be induced by tunicamycin, suggesting that it might be the 78-Kd glucose-regulated protein (GRP78). The identity of the 78-Kd protein with GRP78 was confirmed by limited chymotryptic mapping and immunoprecipitation analysis. Preferential synthesis of GRP78 in dexamethasone-treated cells was not secondary to alterations in the glycosylation of cellular proteins. Significantly, steady-state levels of GRP78 mRNA were unchanged following dexamethasone treatment. Preferential synthesis of GRP78 in glucocorticoid-treated S49 cells may reflect the unique property of GRP78 mRNA to be translated under conditions that interfere with the translation of most other cellular mRNAs. GRP78 is a highly conserved protein that is essential for cell viability. Preferential synthesis of GRP78 may be a protective response to metabolic events that interfere with normal mRNA translation in glucocorticoid treated mouse lymphoma cells. PMID- 1596570 TI - Prognostic implications of evaluation for lymph node involvement by T-cell antigen receptor gene rearrangement in mycosis fungoides. AB - We investigated the correlation between the detection of clonal rearrangement of the T-cell antigen receptor gene (TCRR) in lymph node tissue with histopathologic lymph node classification in 33 patients with mycosis fungoides with and without the Sezary Syndrome. We analyzed DNA extracted from lymph nodes that were histologically uninvolved (LN1-2), dermatopathic nodes with clusters of atypical cells (LN3), and nodes effaced with lymphoma (LN4) and found TCRR in none of five LN1-2 nodes, 8 of 17 LN3 nodes, and 10 of 11 LN4 nodes. Further, the detection of TCRR correlated with presence of palpable adenopathy (P2 less than .0001) and was associated with a worse survival (P2 = .0024). Within the subgroup of patients with LN3 nodes, there was a trend (P2 = .14) toward inferior survival if nodes were involved by TCRR, irrespective of extent of skin disease. We conclude that detection of TCRR in nodes from mycosis fungoides patients is an objective and reliable means of assessing tumor infiltration of lymph node and is associated with an inferior survival. PMID- 1596571 TI - Fluorescence in situ hybridization: a sensitive method for trisomy 8 detection in bone marrow specimens. AB - Trisomy 8 is a common anomaly in bone marrow (BM) cells of patients with myeloproliferative disorders (MPD), myelodysplastic syndromes (MDS), or acute nonlymphocytic leukemia (ANLL). We studied the efficacy of fluorescence in situ hybridization (FISH) detection of trisomy 8 in patients with MPD, MDS, or ANLL using directly labeled fluorescent alpha-satellite and whole chromosome paint (WCP) DNA probes specific for chromosome 8. Using FISH, we analyzed interphase nuclei and metaphase spreads from randomized series of BM specimens from normal individuals and patients with varying proportions of trisomy 8 as determined by conventional cytogenetic analysis. The BM of all normal donors contained less than or equal to 2.0% nuclei with 3 interphase FISH signals and less than or equal to 1 metaphase with 3 WCP FISH signals. Ninety-five percent and 98% of BM specimens with at least two metaphase cells with trisomy 8 by cytogenetic analysis contained greater than 2.0% nuclei with 3 interphase FISH and greater than 2 metaphases with 3 WCP FISH signals, respectively. Thirteen patients had 1 in 20 or 1 in 30 metaphase cells with trisomy 8 by conventional cytogenetic studies. Of these patients, four had greater than 2.0% nuclei with 3 interphase FISH signals. The BM of all four patients contained positive metaphase FISH results. We then studied the usefulness of FISH analysis to detect occult trisomy 8 by analyzing BM nuclei from 144 patients who had MPD, MDS, or ANLL and either 20 normal metaphase cells or an abnormal karyotype without trisomy 8. Seven patients had greater than 2.0% nuclei with 3 interphase FISH signals (range, 2.10% to 3.40%) and six patients had 2 or more cells with trisomy 8 upon metaphase FISH or extensive conventional cytogenetic analysis. Our results show that interphase and metaphase FISH analyses are useful methods to detect trisomy 8 cells in BM specimens, especially for specimens with normal or uncertain conventional cytogenetic results. PMID- 1596572 TI - Trisomy of leukemic cell chromosomes 4 and 10 identifies children with B progenitor cell acute lymphoblastic leukemia with a very low risk of treatment failure: a Pediatric Oncology Group study. AB - To account for the superior prognosis of hyperdiploid, B-progenitor acute lymphoblastic leukemia (ALL), we investigated the influence of trisomy in 1021 children greater than or equal to 1 year old by recursive partitioning analysis. The patients were treated according to a stratified, randomized study testing antimetabolite-based therapies. Trisomies of several individual chromosomes were associated with a better prognosis in a univariate statistical analysis. Of greater importance, trisomy of both chromosomes 4 and 10 identified a subgroup of patients (n = 180) with an extremely favorable 4-year event-free survival (EFS). Combined trisomy of chromosomes 4 and 10 retained its prognostic significance after stratification of patients by DNA index, age, and leukocyte count. Among patients with a DNA index greater than 1.16, patients with trisomies of both chromosomes 4 and 10 had a 4-year EFS of 96.6% (n = 161, SE = 3.8%), whereas patients with neither or only one of these trisomies had a 4-year EFS of 70.4% (n = 73, SE = 11.5%). All 19 patients with a DNA index less than or equal to 1.16 but with trisomies of chromosomes 4 and 10 remain in remission, suggesting that favorable chromosome trisomy dominates in a situation in which the cellular DNA content of less than or equal to 1.16 predicts a less favorable outcome. We conclude that combined trisomy of chromosomes 4 and 10 independently predicts EFS among children with B-progenitor ALL. Patients within the B-progenitor group who have this feature (about 20% of those with clonal abnormalities) are likely to be cured with antimetabolite-based chemotherapy--an approach that should produce few significant late effects. PMID- 1596573 TI - The translocation t(1;22)(p13;q13) is a nonrandom marker specifically associated with acute megakaryocytic leukemia in young children. AB - We present the nonrandom occurrence, frequency, and degree of immunophenotype association of the t(1;22)(p13;q13) in children with acute nonlymphocytic leukemia (ANLL). This karyotype anomaly occurred in leukemia cells from five of 445 (1.1%) children with newly diagnosed ANLL who were successfully studied by cytogenetic analysis at four European centers between January 1987 and January 1992. The occurrence of the t(1;22) was restricted to the French-American-British classification (FAB) subtype M7. The overall incidence in children with acute megakaryocytic leukemia (AMKL) was 27.8% (5/18 cases); in infants with AMKL, the frequency of the t(1;22) was 66.7% (4/6 cases). Three of the patients carrying this anomaly had a diploid karyotype, whereas in two cases a hyperdiploid karyotype was found. However, in all five patients, the t(1;22) was the only translocation event present at diagnosis. All patients received aggressive chemotherapy for acute myelogenous leukemia (AML). Two patients died within 15 months of diagnosis without entering remission. One of three patients who entered remission died 7 months after diagnosis, most likely from intramedullar hemorrhage. Only two of the five children with the t(1;22) who received autologous bone marrow transplantation (BMT) are alive and in complete remission (CR) 23 and 40 months after diagnosis, respectively. At the time of diagnosis, the age of the oldest child carrying the t(1;22) was 18 months. The cases with this chromosome anomaly were compared with an age-matched group of five children with AMKL lacking this translocation. The patients with the t(1;22) had a lower median value of the peripheral white blood cell (WBC) count and a higher median hemoglobin level than the patients from the matched group. In the latter cases, normocellular or hypercellular bone marrow (BM) was detected at diagnosis. In contrast, all children with the t(1;22) in our series had a hypocellular BM. Histological BM analyses were available in three of these patients and showed marked fibrosis. Other clinical and laboratory parameters showed no obvious differences between the matched groups. Despite intensive chemotherapy, AMKL in children appears to be associated with a poor prognosis. The clinical courses of the children with AMKL and the t(1;22) presented may be indicative of a beneficial effect of autologous BMT in this subset of patients. PMID- 1596574 TI - Inhibition of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL 1 beta) messenger RNA (mRNA) expression in HL-60 leukemia cells by pentoxifylline and dexamethasone: dissociation of acivicin-induced TNF-alpha and IL-1 beta mRNA expression from acivicin-induced monocytoid differentiation. AB - We have previously noted that the glutamine antagonist acivicin (alpha S,5S-alpha amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid) induces monocytoid differentiation of freshly isolated human myeloid leukemia cells and cells of the myeloid leukemia cell line HL-60, and that the differentiation is accompanied by increases in expression of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). Because we also showed that TNF-alpha and IL-1 beta can act synergistically to cause monocytoid differentiation of HL-60 cells, we hypothesized that acivicin-induced TNF-alpha and IL-1 beta, in an autocrine manner, caused the differentiation. The purpose of the present study was to determine the causal roles of TNF-alpha and IL-1 beta in the acivicin-induced differentiation of HL-60 cells by the use of dexamethasone (DEX) and pentoxifylline (PTX), two drugs that effectively inhibit expression of TNF-alpha and IL-1 beta. Acivicin caused a monocytoid differentiation of the cells as manifest by diminished cell growth, morphologic maturation of the cells, increased ability to generate hydrogen peroxide in response to acute treatment with phorbol myristate acetate, and increased expression of nonspecific esterase and the surface antigens CD14 and CD11b. Acivicin treatment also caused the cells to have diminished steady-state expression of messenger RNA (mRNA) for c-myc and c-myb, and increased expression of mRNA for TNF-alpha and IL-1 beta. DEX and PTX did not alter cell growth, and did not block the acivicin-induced block in growth. PTX caused a slight increase in nonspecific esterase expression, but DEX had no effect on this, and neither drug diminished the acivicin-induced increase in nonspecific esterase. Although neither drug alone lessened the acivicin enhancement of hydrogen peroxide production, DEX and PTX together reduced this. DEX did not modify the acivicin-induced morphologic maturation of the cells, but PTX alone or PTX with DEX potentiated the acivicin-induced increase in mature cells. Basal CD14 and CD11b expression were slightly reduced by DEX and PTX, but neither drug modified the acivicin-induced increases. DEX and PTX reduced the acivicin-induced increases in TNF-alpha and IL-1 beta mRNA expression, but they had little or no effect on the acivicin-induced decreases in expression of mRNA for c-myc and c-myb. Thus, DEX and PTX effectively block the acivicin-induced expression of TNF-alpha and IL-1 beta, but they have little influence on the acivicin-induced differentiation process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596575 TI - Deamidation of human erythrocyte protein 4.1: possible role in aging. AB - The human erythrocyte membrane protein 4.1 exists in two major electrophoretic forms: 4.1a (80 Kd) and 4.1b (78 Kd). Mass spectrometry and amino acid analysis of the proteolytic peptides derived from carboxyl-terminal regions of these proteins indicate that they differ by deamidation of two aspargine residues at positions 478 and 502. Electrophoretic analysis of carboxyl-terminal peptides has shown that the mobility difference between the two polypeptides is due to the deamidation of Asn502 and not that of Asn478. This observation was confirmed by converting a congener of the protein 4.1b to 4.1a by site-directed mutagenesis of Asn502 to Asp. These results unambiguously demonstrate that deamidation of Asn502 is responsible for conversion of protein 4.1b to 4.1a. Since the conversion of protein 4.1b to 4.1a, under physiological conditions, occurs in a time-dependent manner, our study clearly shows that deamidation is an excellent marker for red blood cell aging. PMID- 1596576 TI - Phase I-II trial of a monoclonal anti-tumor necrosis factor alpha antibody for the treatment of refractory severe acute graft-versus-host disease. AB - In a multicenter pilot study, 19 patients with severe acute graft-versus-host disease (aGVHD) refractory to conventional therapy and serotherapy with a monoclonal anti-interleukin-2 receptor antibody were treated by in vivo infusion of a monoclonal anti-tumor necrosis factor alpha (TNF alpha) antibody (B-C7). Ten patients were grafted from a genotypically identical sibling, five from an HLA mismatched family member, and four from an HLA-matched unrelated donor. Before B C7 treatment, 15 patients had grade IV and four had grade III GVHD. In all cases, patients received cyclosporine/methotrexate as aGVHD prophylaxis. Patients were administered increasing doses of antibody (from 0.1 to 0.4 mg/kg). The antibody was infused in bolus daily for 4 days and then every other day twice (6 doses). No side effects were observed during treatment regardless of the dose level used. Changes in peripheral blood cell counts occurred in 8 of the 19 patients and appeared to be unrelated to B-C7. No truly complete response was observed; eight patients achieved a very good partial response (42.6%) and six a partial response (31.5%). The treatment was ineffective in five patients (26.4%). When present, the response occurred early (less than 3 days). In the 14 responding patients, gut lesions responded best (100%), followed by skin (85%) and liver (35.7%) lesions. In 9 of 11 evaluable patients (81%), GVHD recurred when treatment was discontinued in a median delay of 3 days (range, 2 to 120 days). All except one died from aGVHD. Two patients did not experience GVHD recurrence and are still alive 13 and 18 months post-bone marrow transplantation. This pilot study shows that a monoclonal anti-TNF alpha antibody may be of benefit to some patients with severe refractory aGVHD, but is ineffective to prevent GVHD recurrence in the majority of cases. PMID- 1596577 TI - T-cell-depleted allogeneic bone marrow transplantation in adults with acute nonlymphocytic leukemia in first remission. AB - We prospectively evaluated the efficacy of T-cell-depleted bone marrow transplantation (BMT) in adults with de novo acute nonlymphocytic leukemia (ANLL) in first complete remission (CR), with regard to relapse-free survival and incidence of graft-versus-host disease (GvHD). Thirty-one patients older than 16 years (range, 16.5 to 43.2) received T-cell-depleted grafts for this purpose from related HLA/MLC-compatible donors. Twelve of the patients were older than 30 years at the time of transplantation. Patients were prepared with hyperfractionated total body irradiation (HFTBI; 1,375 to 1,500 cGy) and high dose cyclophosphamide (120 mg/kg). T cells were removed from the marrow grafts by a two-step soybean lectin agglutination and sheep red blood cell (sRBC)-rosette procedure, achieving a 2.5- to 3-log depletion of clonable T lymphocytes. No additional prophylaxis against GvHD was administered. The median age at transplantation was 28.8 years; the median interval from diagnosis to transplantation was 3.8 months, and from CR was 2.7 months. Seventy-four percent received consolidation after remission induction therapy. The product-limit estimate of disease-free survival (DFS) at 3 years is 45% (95% confidence interval [CI], 24% to 66%), and the cause-specific probability of relapse is 13%. The median follow-up of the survivors is 72 months (range, 34.5 to 95.6). Median time to achieve a sustained absolute neutrophil count of 500 or greater was 16 days, and to maintain an untransfused platelet count of 20,000 or greater was 20 days. Five patients suffered immune-mediated graft rejection. Three patients developed grade I to II acute GvHD limited to the skin, which resolved promptly with brief courses of systemic steroids. None of the patients has developed clinically apparent chronic GvHD or a secondary lymphoproliferative disorder, and no patient is receiving immunosuppressive therapy. T-cell-depleted BMT by the method reported here is a favorable option as postremission therapy for adults with de novo ANLL in first remission who have an HLA/MLC-compatible related donor, and it is not associated with an increased risk of relapse posttransplant. PMID- 1596578 TI - Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin. AB - Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies. PMID- 1596579 TI - Absence of the gamma-Leu 427 (gamma') variant in the platelet alpha-granular fibrinogen pool supports the role of glycoprotein IIB/IIIA in mediating fibrinogen uptake into platelets/megakaryocytes. PMID- 1596580 TI - Thoracoscopic lymph node dissection in the staging of esophageal carcinoma. AB - Preoperative staging in esophageal cancer is usually done by noninvasive tests. Currently, in the staging of lung cancer, when lymph nodes are identified preoperatively by CT or MRI to be greater than 1 cm, surgical staging using mediastinoscopy, Chamberlain procedures, or thoracoscopy are employed. We describe herein the use of thoracoscopy in routine preoperative staging of esophageal cancer. With the advent of newer laparoscopic techniques currently available, thoracoscopy plays an increasing role in the management of intrathoracic disease. Staging thoracoscopy as a routine preoperative invasive staging test appears to be a good diagnostic test. PMID- 1596581 TI - ras oncogene detection in pre-neoplastic lesions: possible applications for diagnosis and prevention. AB - The development of methodologies for the early detection of genetic mutations is an important issue in the prevention and treatment of malignancy. Current knowledge of the association of specific genetic alterations with the development of certain types of tumors enables us to approach the early detection of cancer long before histologic or pathologic evidence indicates the development of neoplastic tumor growth. The identification of genetic alterations as biological markers allows for early diagnosis, which in turn may dictate a particular regimen of treatment to prevent subsequent tumor development. This commentary presents an evaluation of the current status of procedures for the early detection of mutations in the ras oncogene family and their relevance to diagnosis and prevention of neoplastic disease. PMID- 1596582 TI - Non-enzymatic activation of procarbazine to active cytotoxic species. AB - The cellular cytotoxicity of procarbazine is thought to result from bioactivation of the parent compound through reactive intermediates to an ultimate alkylating species. Procarbazine is converted initially to azoprocarbazine, which is then N oxidized through a cytochrome P-450-mediated process to a mixture of the positional isomers, benzylazoxyprocarbazine and methylazoxyprocarbazine. In order to define the bioactivation events that lead to the cytotoxic species, the in vitro cytotoxicities of the purified azoxy isomers as well as of the parent compound, procarbazine, were evaluated with the human leukemia cell line, CCRF CEM. The methylazoxy isomer was found to be the most active species. Procarbazine inhibited the growth of CCRF-CEM cells but at a concentration much higher than that required for the methylazoxy isomer. Since procarbazine must be metabolized to form the cytotoxic species, we sought to determine if the active metabolite, methylazoxyprocarbazine, was being formed in the incubations. Solutions of procarbazine incubated with and without cells at 37 degrees C were analyzed by combined liquid chromatography-mass spectrometry with a thermospray interface. The azoxy metabolites of procarbazine appeared rapidly in cellular incubations and in the aqueous solutions without cells. More of the methylazoxy isomer was formed initially, but by 72 hr the benzylazoxy isomer was the predominant species. Thus, in these studies it appears that procarbazine was benzylazoxy isomer was the predominant species. Thus, in these studies it appears that procarbazine was non-enzymatically oxidized to the two azoxyprocarbazine isomers and that the methylazoxy compound was the most cytotoxic to CCRF-CEM cells. PMID- 1596583 TI - Quantitation of dihydrofolate reductase and thymidylate synthase mRNAs in vivo and in vitro by polymerase chain reaction. AB - Rapid and quantitative polymerase chain reaction (PCR) assays based upon the competitive template technique have been developed for human dihydrofolate reductase (DHFR; E.C.1.5.1.3) and thymidylate synthase (TS; E.C.2.1.1.45) mRNAs. In various tumor cell lines and clinical tumor biopsies, TS mRNA levels correlated with TS levels as determined by [3H]-fluorodeoxyuridylate binding. Levels of DHFR and TS mRNAs, determined by PCR, correlated with mRNA quantitation by conventional dot blot methodology. The ratio of TS/DHFR mRNAs in a number of human carcinoma cell lines varies from 0.4 to 9.9 but ranges from 1 to greater than 1.5 x 10(3) in a number of tumor samples. Differences in the TS/DHFR mRNA ratio in tumors as compared with cultured cells reflects low levels of DHFR mRNA in some tumors. In patients treated with a combination of 5-fluorouracil and leucovorin, mRNA levels for TS increased approximately an order of magnitude in tumor samples 4 and 24 hr after drug treatment, whereas TS levels decreased. These results have significance for the biochemical pharmacology of antifolates and fluorinated pyrimidines in vivo and the relevance of cell culture models for antifolate chemotherapy and drug resistance. PMID- 1596584 TI - Azidothymidine and dipyridamole as biochemical response modifiers: synergism with methotrexate and 5-fluorouracil in human colon and pancreatic carcinoma cells. AB - Azidothymidine (AZT), inhibiting thymidine kinase (EC 2.7.1.21) (Weber, G. et al., Cancer Commun. 2:129-133, 1990) and dipyridamole, inhibiting nucleoside transport (Zhen, Y.-s. et al., Cancer Res. 43:1616-1619, 1983) exert blocking action on the activities of salvage pathways of nucleotide biosynthesis. Determined by clonogenic assay in human colon cancer HT-29 cells, the cell survivals for AZT, 10 microM, dipyridamole, 5 microM, and methotrexate (MTX), 0.025 microM, were 90, 82, and 62%, respectively; while the combinations of AZT + MTX, dipyridamole + MTX and AZT + dipyridamole + MTX, reduced survivals to 36, 4.3, and 0.7%. AZT or dipyridamole was synergistic with MTX, whereas AZT plus dipyridamole showed an even more marked potentiation of MTX activity. The survivals for 5-fluorouracil (5-FU), 0.5 microM, alone, AZT + 5-FU, dipyridamole + 5-FU, and AZT + dipyridamole + 5-FU were 86, 47, 29 and 5.1%, respectively. Similar results were observed in human pancreatic carcinoma BxPC-3 and PANC-1 cells. AZT markedly enhanced the inhibitory effect of dipyridamole in reversing the thymidine-hypoxanthine rescue from MTX cytotoxicity. AZT inhibited [14C]thymidine incorporation into DNA in HT-29 cells and strongly enhanced the effect of dipyridamole. The results indicate that combinations composed of AZT, dipyridamole, and antimetabolites, such as MTX and 5-FU, are potentially effective in the chemotherapy of human neoplasias. PMID- 1596585 TI - Reference listings in cancer research. PMID- 1596586 TI - Epidemiology of haematological disease: Part I. PMID- 1596587 TI - Acute leukaemias. PMID- 1596588 TI - Tuberculosis and the haemopoietic system. PMID- 1596589 TI - Neonatal jaundice in Asia. AB - Neonatal jaundice is a major clinical problem globally, especially in the Asian and south-east Asian regions. There is no universal definition of hyperbilirubinaemia, and comparisons of management and control of hyperbilirubinaemia in infants at different centres are difficult. G6PD deficiency, ABO incompatibility, low birth weight and sepsis are the common causes of neonatal jaundice, but there is a group of babies whose cause of neonatal jaundice has yet to be found. Genetic factors may be responsible for ethnic differences in the ability to eliminate bilirubin, while unidentified environmental factors may also play a role in the prevalence of neonatal jaundice. As a result of a surveillance programme for neonatal jaundice in Singapore, involving health education of doctors, nurses and the lay public, screening of the newborn and the early treatment of jaundice, we have not seen a single case of kernicterus in Singapore for more than 10 years. PMID- 1596590 TI - Nutritional anaemias. AB - Nutritional anaemia is recognized as a major public health problem throughout the world, especially in developing countries. Infants, young children, menstruating women and, in particular, pregnant women are most frequently affected. Sufficient evidence suggests that iron deficiency is the most common cause of nutritional anaemia in the world. Folate deficiency is considered as the second most common cause. In this chapter we discuss the factors determining nutritional inadequacy in iron and folate requirements versus iron and folate intake, particularly in different age/sex categories; the amounts of iron and folate involved in daily exchange and the role of the diet and physiological and pathological variations in losses and requirements are reviewed. The consequences in terms of health of iron and folate deficiencies and methods for assessing iron and folate status of populations are also presented. PMID- 1596591 TI - Hereditary and nutritional iron overload. PMID- 1596592 TI - Molecular epidemiology of the thalassaemias (including haemoglobin E). AB - The thalassaemias are the most common genetic disorders of man, and over the last decade the molecular epidemiology of these defects has been studied in detail. After briefly reviewing the great diversity of mutations giving rise to these conditions, four global regions are discussed in more detail. The thalassaemias, of which haemoglobin E is one, are most frequent in Asia, where recent work has defined the molecular basis of the beta thalassaemias and the frequencies of the various types of alpha + and alpha 0 thalassaemia. Oceanic populations have a range of globin gene variants remarkably different to those of south-east Asia. Most is known about the nature and frequencies of thalassaemia mutations in Mediterranean countries, where prenatal diagnosis programmes have been very successful in reducing the frequency of new cases of thalassaemia major. alpha + Thalassaemia is the most common haemoglobinopathy in sub-Saharan Africa, and molecular studies of American Blacks with beta thalassaemia have elucidated the probable molecular basis of the mild form of this disorder in Africans. Although each geographical region has its own group of common beta thalassaemia mutations, with little overlap, most of these appear to have had a single origin. The question of single or multiple origins for HbE in south-east Asia is unresolved. Recombination events producing alpha + thalassaemia deletions are frequent, whereas alpha 0 thalassaemia is produced by a variety of large deletions, each of which has had a single origin. The evidence favouring natural selection by P. falciparum malaria as the primary cause of high frequencies of the thalassaemias throughout the tropics and subtropics is reviewed. While the mechanism of protection remains unclear, epidemiological evidence supporting the hypothesis is strong, but more information is required from case-control studies on the amount of protection provided by the various thalassaemia genotypes. PMID- 1596593 TI - Compliance aids--do they work? AB - The decision to use a compliance aid will depend on the motivation of the patient, their specific medication regimen, and their physical and cognitive ability. The administration of oral medicines may be facilitated through the appropriate use of 'organisers' which act as aides memoire. 'Medidos' and 'Dosett' are the most frequently studied compliance aids and both have been shown to be beneficial to the elderly and to community-based psychiatric patients. Adherence to a medication regimen may be improved without the use of proprietary compliance aids by ensuring that the most appropriate traditional container is used and by paying attention to the highest standard of labelling on the medicine container. Gadgets that are designed to improve physical dexterity can be useful when applying topical preparations, administering insulin injections, operating pressurised inhalers or administering eyedrops. The accurate administration of eyedrops is particularly important when treating glaucoma and may be facilitated by using devices that are designed to help with aiming of the eyedrops ('Easidrop', 'Mumford Auto-drop,' 'Opticare'). If squeezing the eyedrop container is a problem the 'Opticare' device may be particularly suitable. There may be value in the use of the compliance aids to provide assistance to carers who become involved with preparing medication for patients. Selection of an appropriate compliance aid is not likely to be the total solution to inadequate adherence and most patients will require a combination of strategies to facilitate adherence to treatment with medicines. PMID- 1596594 TI - Current drug therapy for Parkinson's disease. A review. AB - The impact of neuropharmacology has been greatest in 2 areas of clinical treatment: epilepsy and Parkinson's disease. This article covers the drug treatment of Parkinson's disease, a condition which characteristically affects the elderly population. The 5 drugs or groups of drugs used in the treatment of Parkinson's disease are: (a) anticholinergic drugs; (b) amantadine; (c) levodopa plus a peripheral decarboxylase inhibitor; (d) dopamine agonists; and (e) selegiline. Levodopa is still the most effective anti-Parkinsonian drug for most patients and is often combined with selegiline which may retard the rate of disease progression. The early use of dopamine agonists (such as bromocriptine) may prevent the subsequent development of response fluctuations. Once fluctuations have developed, they may be helped by the use of slow release levodopa preparations and, in the most severe cases, subcutaneous apomorphine. PMID- 1596596 TI - Minimising the side effects of cancer chemotherapy in senior patients. AB - Over 50% of cancer deaths occur in persons aged over 65 years, but because of presumed increased toxicity of chemotherapeutic agents in the elderly, they are frequently treated with reduced doses. However, a review of the literature suggests that chronological age alone does not account for increased toxicity in the elderly. If changes in physiological function, the presence of other illness, and the use of concomitant drugs are taken into consideration, chemotherapy can be used safely and effectively in the elderly. However, this knowledge must be used with the understanding that while response rates are not lower in the elderly, the cancers most commonly encountered are notoriously unresponsive to chemotherapy. Thus, a strategy to use chemotherapy safely and effectively in the elderly involves careful selection of those cancers to be treated, full assessment of the patient's physiological functions, and a knowledge of the adverse effects of the individual agents used. Finally, the use of a limited treatment plan and an understanding of the principles of symptom relief can help optimise treatment throughout the course of the cancer. PMID- 1596595 TI - Pharmacological approaches to the treatment of intermittent claudication. AB - Intermittent claudication is a common condition of the elderly, occurring in 3 to 20% of individuals over the age of 65 years. Although local disease is usually benign, life expectancy in patients with intermittent claudication is reduced by approximately 10 years due to associated cardiovascular mortality. Several classes of drugs have been used in intermittent claudication, but clinical studies evaluating their efficacy leave much to be desired. Pentoxifylline (oxpentifylline), a rheological agent, and naftidrofuryl, an enhancer of aerobic metabolism, are the 2 most widely investigated and utilised drugs. The combined results of 10 placebo-controlled studies with pentoxifylline and 4 with naftidrofuryl estimate increases in claudication distances of 51 and 42%, respectively. However, due to publication bias, these figures are probably overestimates of the true benefit from treatment with these drugs. It is likely that any benefit from pentoxifylline or naftidrofuryl is small and of little clinical importance. The suggestion that naftidrofuryl has greater efficacy in older patients remains unproven. Other classes of drugs including vasodilators, antiplatelet drugs, anticoagulants and prostaglandins have not been shown to be effective. Only 2 approaches to the management of intermittent claudication have been shown convincingly to be of benefit: stopping smoking and exercising regularly. PMID- 1596597 TI - Methodological problems in assessing therapeutic efficacy in patients with dementia. PMID- 1596598 TI - Clinical trials and clinical practice in the elderly. A focus on hypertension. PMID- 1596600 TI - [Current comments on Freud's treatment of "The question of lay analysis"]. AB - The author gives a review on Freud's basic thoughts on lay analysis from 1926 and proceeds with the question why the Deutsche Psychoanalytische Vereinigung (German Psychoanalytic Association) admits only such candidates for psychoanalytic training who are physicians or psychologists. This corresponds with the policies of German health insurance agencies, which include only physicians directly or psychologists indirectly in their plans. He suggests that this attitude derives from a limited view of psychoanalysis, for which he names three different reasons: historical, institutional, and those that grow out of the specifics of psychoanalytic practice. PMID- 1596599 TI - Treatment recommendations for anticonvulsant drug therapy in the older patient. AB - Seizures in older individuals are frequently due to cerebrovascular disease, though other causes, such as primary or metastic brain tumour, must be considered. Recurrence after a first seizure may be as high as 83% by 3 years, suggesting that withholding an anticonvulsant after a first seizure may not be wise. Some older patients may be more sensitive to anticonvulsant side effects, so treatment with 1 drug is encouraged, with monitoring of blood concentrations of the anticonvulsant during initiation of therapy. Interaction of anticonvulsants with other drugs is less of a problem than may be expected, but should be kept in mind. The treatment of status epilepticus should be aggressive. PMID- 1596601 TI - [Can transference interpretation as expert evaluation be analyzed?]. AB - Usually the patient is excluded from the evaluation procedure which is necessary to carry out psychotherapy or psychoanalysis. Neither does he know the report of his treating analyst to the expert, nor the latter's report to the medical insurance company that covers the cost of his treatment. In his article, the author suggests to include the patient actively in this process, by giving him access to the evaluation procedure. He maintains that, as long as the procedure is unknown to the patient, its subconscious meaning cannot be analysed, and the analyst's contribution to the process of transference in this area remains obscure. PMID- 1596603 TI - Nurse's role in ethical decision making. PMID- 1596602 TI - Box Hill Hospital Intensive Care Unit. AB - The Unit Profile of the Intensive Care Unit at Box Hill Hospital describes the Unit's history and the progression it has made through the past 26 years. Details are given on the type of patients received and the catchment areas this Unit services. The organisational structure and the educational services available are discussed. The breakdown of staff including the nursing and medical staff and the available ancillary services as stated. The critical care course is described in detail to give an outline of and to promote this tertiary based course. It is also hoped this will encourage other hospitals and tertiary institutions to structure such similar courses to provide a more professional education for nurses. PMID- 1596604 TI - Putting pen to paper. PMID- 1596605 TI - The intensive care management of severe pregnancy induced hypertension. AB - Severe pregnancy induced hypertension (PIH, pre eclampsia) is a disease which is now treated in the intensive care unit rather than with sedation in a dark room. The pathophysiology is now well understood and allows for better and more effective management. This paper looks at the strict haemodynamic monitoring and management required to prevent complications such as eclampsia, DIC, HELLP syndrome, maternal and foetal death. The nurse's role in the management of severe PIH is discussed. PMID- 1596606 TI - Hospitals in Australia are all experiencing financial crisis in varying degrees. PMID- 1596607 TI - The role of the nurse in advanced life support. PMID- 1596608 TI - The use of exit interviews in health service facilities. AB - Exit Interviews, also known as termination or separation interviews, are conducted in some hospitals and other health service agencies as a routine procedure when staff are ending their period of employment. The major purpose of these interviews is to elicit data regarding the employee's working experience in the organization and hence identify those factors that enhance retention of staff, for example, job satisfaction, study opportunity, challenging milieu, and those that are contributory factors to the decision to resign, such as, dissatisfaction due to poor standards of care becoming the norm and lack of autonomy in planning and implementing nursing care. As a recent study indicated, the hierarchical level of the Exit Interviewer could have a significant effect on the amount and accuracy of the data so obtained. While applicable to all departments of a facility, comments herein are largely concerned with nursing and are based on a thesis by the author. PMID- 1596609 TI - Paediatric pain--concepts for caring. AB - Caring for the health of children is a relatively modern concept. Furthermore, recognition of children's need for relief from pain is only just beginning to emerge and remains a subject of controversy. Sadly, in the past, children's pain was viewed as a diagnostic aid rather than an entity in its own right. This paper outlines historical perspectives which contributed, not only to the slow evolution of paediatric nursing, but in particular, to recognition of children's pain as an entity. Furthermore, it emphasizes the importance of a sound understanding of children's developmental stages as fundamental to accurate assessment of children's special needs which can only be determined through effective communication. Fundamentally, as children remain a somewhat voiceless, powerless minority group, health professionals are challenged not only to provide care, but to ensure that the care they give is indeed meeting the unique needs of each and every individual child. PMID- 1596610 TI - Erosion of the role of the nurse. PMID- 1596611 TI - Caring for those who care. PMID- 1596612 TI - A case for advocacy. PMID- 1596613 TI - Perceived sources of stress among student nurses. AB - Questionnaire data was collected from a sample of 306 student nurses from three institutions (university, college of advanced education and hospital) during the second week of the first year of their course, and from 189 students from two of the institutions (university and CAE) at the conclusion of their first year of education. The main sources of stress on both occasions were essentially the same for women and men, and for students from the different institutions. These concerns focussed on study-related issues, the emotional demands of nursing, the use of technical equipment, interpersonal interaction, and lack of time for family and personal pursuits. It was suggested that these concerns could be reduced through the introduction of education in study skills, the provision of the opportunity to gain hands-on experience with technical equipment, and the development of social skills. PMID- 1596615 TI - Lifetime memories. PMID- 1596614 TI - Learning by experience. PMID- 1596616 TI - Managing a 'difficult' client: an insight orientated approach. PMID- 1596617 TI - The social construction of nursing. AB - The struggle that nursing has experienced to gain just status and financial reward can be explained, at least in part, by examining dominant ideologies in Australian society today. For example, such ideologies devalue caring in various ways, and since caring is a basic tenet of nursing, these ideologies ultimately devalue nursing itself. This paper explores the way in which the image and role of nursing has been socially constructed in light of such hegemonic assumptions. PMID- 1596618 TI - Re-thinking the law, and challenging its traditional role in nursing's affairs: a strategy for professional reform. AB - Nurses world wide have regarded the law as a powerful tool of professional reform, and have historically looked to the law (its system and processes) to enhance and advance their professional goals. Nevertheless, the nursing profession still has not achieved its ultimate goals. To this day, nurses lack legitimated status as autonomous professionals, and are still burdened with enormous responsibility without the authority to match it. Given that the law is such a powerful tool of professional reform, the question must be asked at this point of nursing history: Why has the nursing profession not received the legal remedies it has sought in its quest to gain legitimated freedom from the subordinate and oppressed position it has historically occupied? In this paper, an attempt will be made to answer this question. PMID- 1596619 TI - Reducing the psychological impact of postoperative pain. AB - This article addresses the nurse's role in reducing the psychological impact of postoperative pain. It deals first with the definition and assessment of pain, the effects of pain and the factors that affect it, and then examines the different measures that may be employed to alleviate it and how effectively these are utilized. PMID- 1596620 TI - Body image in end-stage renal failure. AB - People in renal failure may experience negative reactions to their bodies because of the invasive nature of treatment. Nurses, by utilizing their listening and counselling skills, can help patients come to terms with these feelings, and thus raise self-esteem. PMID- 1596621 TI - Professionalism and the role of the UKCC. AB - Professionalism and the role of the UKCC concern every registered nurse, midwife and health visitor, and yet many practitioners do not understand the complex nature of the concept and the professional body. PMID- 1596623 TI - Profile: a passport to practice? PMID- 1596622 TI - The need for a specialist clinical and educational journal. PMID- 1596624 TI - Nursing in Europe: what 1992 has to offer. AB - RGNs and midwives have been allowed to work freely throughout Europe since 1977. However, the number of migrating nurses remains comparatively low. It is essential that nurses are culturally aware so that alternative healthcare patterns can be accurately evaluated. PMID- 1596625 TI - Role of the nurse advocate. AB - When deciding whether to act as patient advocate, the nurse is faced with a dilemma. If she advocates for the patient she may be in conflict with other healthcare professionals; however, if she does not she may conflict with herself, her code of conduct, and the patient. PMID- 1596626 TI - How to plan your career. AB - Many nurses now feel under enormous pressure to succeed in an increasingly competitive environment. The first step is not to panic but to plan. PMID- 1596628 TI - What is an advanced practitioner? PMID- 1596629 TI - Subjectivity of pain. AB - The aim of this article is to explore the sociopsychophysiological subjective nature of pain, using Melzack and Wall's gate control theory of pain. In addition, the basis of pain control will be examined. PMID- 1596627 TI - Nursing in Zimbabwe during the first decade of independence. AB - The nursing profession has been central to the massive changes occurring in the health services in Zimbabwe since it gained independence. This article examines the restructuring that has taken place within nursing in the post-independence era. PMID- 1596630 TI - Medicine, God, and Aristotle in the early universities: prefatory prayers in late Medieval medical commentaries. PMID- 1596631 TI - The impact of "Fletcherism" on the food policies of Herbert Hoover during World War I. PMID- 1596632 TI - "A long pull, a strong pull, and all together": San Francisco and bubonic plague, 1907-1908. PMID- 1596633 TI - Efficient preachers of the gospel of health: the 1898 scheme for educating Maori nurses. PMID- 1596634 TI - Two in the bush. PMID- 1596635 TI - Philosophical issues in primary health care delivery in New Zealand. PMID- 1596636 TI - Reintroducing: Hilda Bessie Allen (nee Forrester) "Frostie". Interview by Ann Shaw. PMID- 1596637 TI - To create an atmosphere--. PMID- 1596638 TI - Membrane proteins involved in the adherence of Plasmodium falciparum-infected erythrocytes to the endothelium. AB - Plasmodium falciparum (human malaria) infections are characterized by the attachment of erythrocytes infected with mature stage parasites to endothelial cells lining the post-capillary venules, a phenomenon known as sequestration. In the human body, the microvessels of the heart, lungs, kidneys, small intestine, and liver are the principal sites of sequestration. Sequestered cells that clog the brain capillaries may reduce blood flow sufficiently so that there is confusion, lethargy, and unarousable coma--cerebral malaria. This review considers what is known about the molecular characteristics of the surface proteins, that is, the red cell receptors and the endothelial cell ligands, involved in sequestration. Recent work from our laboratory on the characterization of the adhesive proteins on the surface of the P falciparum infected red cell, and the ligands to which they bind on human brain endothelial cells is also discussed. Finally, consideration is given to the multifactor processes involved in sequestration and cerebral malaria, as well as the possible role of 'anti-adhesion therapy' in the management of severe malaria. PMID- 1596639 TI - Reorganization of the apical cytoskeleton of uterine epithelial cells during early pregnancy in the rat: a study with myosin subfragment 1. AB - Actin filaments were identified in the epithelial cells of rat uterus following detergent extraction and decoration of microfilaments (MF) with myosin subfragment 1 (S1). MF connections with cytoplasmic organelles and the apical plasma membrane are also described. Transmission electron microscopy revealed that the regular microvilli of non-pregnant, oestrous animals contain several decorated MF with rootlets descending into a densely filamentous terminal web. Following mating, the actin cytoskeleton was examined on days 1, 3 and 6 of pregnancy. In this period, the irregular projections that replace MV assumed an underlying, dense network of decorated MF, whilst smoother surfaces displayed few cytoplasmic filaments. At the time of blastocyst implantation, a structured terminal web was no longer present. Structural details were revealed concerning the contents of large, bleb-like projections found on the apical surface. PMID- 1596640 TI - Redistribution of microvilli and membrane enzymes in isolated rat proximal tubule cells. AB - Isolated cells from the proximal tubule have previously been used to study specific renal physiological processes. Here we analysed the structural changes induced by mechanical isolation on rat proximal tubule cells. As major modifications we detected: 1) a redistribution of brush border microvilli, which spread out over all the cell surface immediately after isolation; 2) a rapid redistribution of the apical membrane enzyme markers aminopeptidase N and isomaltase; and 3) a striking decrease of membrane surface amplification factor. The results show that cells isolated from the proximal tubule rapidly loose their characteristic polarized membrane structure. Loss of epithelial polarity implies loss of several vectorial transports and should thus be cautiously taken into account when working with this model system. PMID- 1596641 TI - Target cell deformability determines the type of phagocytic mechanism used by Entamoeba histolytica-like, Laredo strain. AB - Morphological study of red blood cell phagocytosis by Entamoeba histolytica-like (Laredo strain) has shown that this amoeba is able to ingest by two distinct mechanisms. One is classical phagocytosis and the other is by suction or microphagocytosis. Rigidification of red blood cells by treatment with glutaraldehyde shows that there is a correlation between the deformability of the ingested cell and the type of phagocytosis observed. Indeed, as the red cells become more rigid, less microphagocytosis is observed. To demonstrate that this shift in phagocytic mechanisms is not induced by the modification of a surface receptor by the glutaraldehyde treatment, the amoebas were fed with erythrocyte ghosts. Since these have lost most of their hemoglobin content, they are less rigid than the intact erythrocytes. The ghosts, even after glutaraldehyde treatment, are always ingested by microphagocytosis. These results have therefore led us to conclude that the type of erythrocyte phagocytosis used by E histolytica-like (Laredo strain) is determined by the deformability of the targetted red blood cells. PMID- 1596642 TI - Calcium-induced acetylcholine release and intramembrane particle occurrence in proteoliposomes equipped with mediatophore. AB - Proteoliposomes obtained from the mediatophore, a purified Torpedo electric organ nerve terminals protein, and endogenous lipids were used for a study of calcium induced release of acetylcholine and freeze-fracture electron microscopy. Large intramembrane particles were induced by the influx of calcium into proteoliposomes, as previously observed for synaptosomes or stimulated electric organ nerve terminals. The involvement of mediatophore in a calcium dependent acetylcholine translocation seems therefore to be related to the occurrence of a category of intramembrane particles in the course of the release process. PMID- 1596643 TI - Comparative studies of protein biosynthesis: the main experimental parameters in pulse and pulse-chase experiments must be standardized. AB - The influence of experimental conditions was investigated in pulse and pulse chase experiments involving L-[35s]methionine incorporation by isolated rat hepatocytes. The incorporation of the labelled amino acid must be linear as a function of dose and time, and similar hepatocyte densities should be used to compare radioactive uptake. High hepatocyte densities give greater precision. In pulse-chase experiments, it was shown that a pool of free radioactivity moves progressively during the chase phase from the intracellular compartment. Protein associated radioactivity must therefore be expressed as a function of both total radioactive uptake and total labelled protein. PMID- 1596644 TI - A radioautographic study of [3H]-A 23187 (calcimycin) in components of the brain. Distribution in different cell types of the diencephalo-mesencephalic roof. AB - The distribution of the ionophore [3H]-A 23187 was examined by means of light and electron microscopy in elements of the central nervous system located in the diencephalo-mesencephalic roof. A 23187 is not evenly distributed in the components studied (ependyma, secretory ependyma of the subcommissural organ and neurons of the mesencephalon). At the cellular level, A 23187 appears preferentially associated with the cytoplasmic membrane as well as with the internal membranous system. PMID- 1596645 TI - Neonatal ECMO praise. PMID- 1596646 TI - Commentary regarding ECRI response to the use of the Gaymar T-pump in ECMO. PMID- 1596647 TI - High-capacity rechargeable nickel-metal hydride battery systems. PMID- 1596648 TI - Computerized maintenance management systems for clinical engineering. PMID- 1596649 TI - A limited-function IEEE-488 interface for medium-speed data acquisition. PMID- 1596650 TI - Rapid prototyping of interactive software for automated instrumentation in rehabilitative therapy. AB - Rapid prototyping is a quick, efficient way to evaluate new electrical instruments. A hardware interface between a computer and an instrument can be simulated in software. The authors demonstrate the technique of rapid prototyping by developing interfaces for two therapeutic strength-testing devices and an electromagnetic tracker/digitizer. The LabVIEW rapid prototyping software tool was used to create "virtual instruments," which combine to form interfaces. The functions and connections of each virtual instrument are described. PMID- 1596651 TI - The feasibility of spectrophotometric measurements of arterial oxygen saturation from the fetal scalp utilizing noninvasive skin-reflectance pulse oximetry. AB - In in-vivo animal experiments, the authors evaluated the feasibility of measuring arterial oxyhemoglobin saturation (SaO2) noninvasively during simulated delivery conditions with a skin-reflectance pulse oximeter sensor attached to the fetal scalp. The optical reflectance sensor consisted of three pairs of red and infrared light-emitting diodes and a concentric array of six identical photodiodes. Two prototype sensor assemblies, incorporating different means of attachment to the scalp, were evaluated. Each sensor was interfaced to a commercial Datascope ACCUSTAT transmittance pulse oximeter, adapted to perform as a reflectance pulse oximeter. This method, once successfully developed, could potentially be used in combination with other fetal monitoring techniques to elucidate the role of noninvasive pulse oximetry in reducing fetal morbidity and mortality. PMID- 1596652 TI - Issues related to surgical gloves. PMID- 1596653 TI - Changing requirements for glove selection and hand protection. PMID- 1596654 TI - Understanding latex. PMID- 1596655 TI - Trends in glove product and process development. PMID- 1596656 TI - Latex allergy. PMID- 1596657 TI - Scalp replantation by arterialised venous network flow-through. AB - A successful clinical case of scalp replantation is presented where a suitable artery could not be identified in the amputated part. Reperfusion of the flap was achieved by an arteriovenous inflow anastomosis and a conventional venous anastomosis for drainage. The aesthetic and physiological success of this case suggests that arteriovenous scalp replantation is a potential avenue for treatment where arterio-arterial repair is not possible. The possible explanation for the success in this patient is the paucity of valves that exist in the venous network of the scalp and forehead, noted in our previous anatomical studies. Knowledge of the replanted tissue venous architecture provides an anatomical basis to understand the potential limitations of arteriovenous replantation. PMID- 1596658 TI - Cancrum oris: functional and cosmetic reconstruction in patients with ankylosis of the jaws. AB - Advances in reconstructive surgery allow treatment of established cases of Cancrum oris with total ankylosis of the jaws to produce a satisfactory functional and cosmetic result. This is achieved by radical excision of scar tissue followed by two layered flap closure of the defect. It is recommended that a cervical flap is used for lining and a deltopectoral flap for cheek cover. Ten patients with Cancrum oris are presented to demonstrate the techniques used. PMID- 1596659 TI - Distal and very distal digital replantations. AB - Ninety-five patients with 98 complete or incomplete amputations of digits are reviewed. Three levels are considered according to the bony lesion, zone III being distal to the nail matrix. In this area, artery, nerve and vein repair need special techniques. The use of leeches in the absence of vein repair does not preclude an acceptable survival rate (68%), compared to the overall series (65.5%); however, smoking is detrimental (52%). Distal replantation is a fast and worthwhile procedure providing acceptable sensibility, no PIP limitation and good appearance at the price of a mean 74 days off work. PMID- 1596660 TI - Intra-arterial 4-hydroxyanisole chemotherapy for locally recurrent malignant melanoma: a re-appraisal. AB - Ten female patients with recurrent cutaneous malignant melanoma (MM) confined to the lower limb were treated with 4-hydroxyanisole (4HA) infused intra-arterially. 10 g of 4HA was infused twice per day up to a maximum dose of 80 g. 4HA infusion caused significant alterations in liver function which precluded completion of the treatment regimen in all but two patients. No tumour regression was observed in any patient. We cannot recommend this technique for managing patients with recurrent cutaneous MM. PMID- 1596661 TI - Primary reconstruction to avoid wound breakdown following groin block dissection. AB - We report our experience of immediate reconstruction of the groin using the deep inferior epigastric artery (DIEA) myocutaneous flap following 32 consecutive ilioinguinal block dissections for groin metastases in patients with penile carcinoma. All groin wounds healed primarily, resulting in a short postoperative hospital stay. Transferring one or both DIEA flaps did not lead to any significant functional disability. PMID- 1596662 TI - The bipedicled free TRAM flap. AB - Unilateral breast reconstruction with all 4 zones of a free TRAM flap was performed in 2 patients with total or near-total transection of the flap by a vertical midline infraumbilical scar. To permit this, both inferior epigastric pedicles were raised and anastomosed to the thoracodorsal vessels and the serratus collateral. Vein grafts were not required and both flaps perfused in toto. The technique is recommended for reconstruction of the larger breast (i.e. where more than a "hemi-TRAM" flap is required for symmetry) in the presence of extensive midline infraumbilical scarring. Avoidance of epigastric bulge, improved vascularity and vastly reduced abdominal wall donor defect give this technique advantages over the conventional bipedicled TRAM flap. PMID- 1596663 TI - Impacted knife injuries of the face. AB - Impacted knife injuries of the face are uncommon. Associated vascular, ocular and neurosurgical injuries should be excluded. The impacted knife should be removed in theatre. Four patients who presented with this injury are discussed. PMID- 1596664 TI - Complications in paediatric craniofacial surgery: an initial four year experience. AB - 107 children undergoing transcranial craniofacial surgery in a paediatric hospital have been reviewed to assess the incidence and type of complications which arose. This represents the first 4 years' experience of the craniofacial team. There were no deaths or permanent adverse sequelae of surgery. A total of 53 complications were seen in 42 patients. In 9.3% of patients they were potentially life-threatening, serious in 12.1% and of a minor nature in 28%. The more serious complications were related either to haemorrhage and/or vasovagal shock at operation or to infection post-operatively. Infants undergoing monoblock frontofacial advancements and those with tracheostomies were at particular risk. PMID- 1596665 TI - Early postoperative complications in primary cleft lip and palate surgery--how soon may we discharge patients from hospital? AB - A retrospective review of the early complications of primary cleft lip and palate surgery in one Plastic Surgery Unit was conducted and the results are presented. Out of 164 primary procedures performed there was an overall complication rate of 26.2%. The life-threatening complications were all related to the respiratory system and all but one of these occurred within 2 days of operation. PMID- 1596666 TI - Leeches: controlled trial in venous compromised rat epigastric flaps. AB - Leeches were studied for their efficacy to improve survival of venous compromised rat skin flaps. In 22 rats, bilateral epigastric island flaps were created and subjected to 6 h of venous occlusion. One flap in each animal was randomised to leech treatment, while the contralateral flap served as its own control. Flap survival, leech feeding time, weight gained by the leech and bleeding time from leech bites were measured. The area of flap survival was significantly increased in leech treated flaps compared to contralateral controls (n = 22 pairs, p = 0.03; Wilcoxon signed rank test). Weight gained in the feeding leech averaged 1.3 +/- 0.2 g (n = 18). Leech feeding time was 107 +/- 13 min (n = 18). Bleeding time from each leech bite averaged 79 +/- 12 min (n = 18). Hence, the extent of flap necrosis resulting from venous impairment can be partly diminished by leech treatment until definitive surgical venous revascularisation. PMID- 1596667 TI - Ultrastructural and surface-area changes of acute and traditionally expanded full thickness skin grafts. AB - The purpose of this study was to determine the effect of expansion on the survival of full thickness skin grafts. In eight pigs 300 ml rectangular tissue expanders were placed into subcutaneous pockets. In four pigs (group I), the expanders were inflated rapidly with a mean 200 ml saline. In the other four pigs (group II), a mean total of 300 ml saline was injected in weekly increments over eight weeks. At the completion of expansion, full thickness skin grafts were taken from the expanded area and sutured back to the donor defects. In both groups surviving graft areas were similar to controls (p greater than 0.06). This study showed that acute and traditional expansion does not lead to increased loss of full thickness skin grafts of the expanded skin. PMID- 1596668 TI - The significance of Eiselsberg and the Viennese school of surgery for the development of reconstructive surgery in Europe. AB - The development of surgery in the second half of the nineteenth century was strongly influenced by the introduction of anaesthesia, asepsis and, last but not least, scientific experimentation. Outstanding in the last respect were the German surgeon Theodor Billroth and his pupils in Vienna. One of them, Anton Freiherr von Eiselsberg, became the spiritual father of the largest surgical school ever founded in Europe. He showed a special interest in plastic surgery. As Eiselsberg started his professorial career in Holland at the University of Utrecht, his relationship to Dutch surgical history has particular significance. PMID- 1596669 TI - "X Lite": a protective shield for skin grafts on the back. AB - "X Lite", a thermoplastic material was used in eight patients as a splint for protecting split skin grafts on the back. After an average stay of 4.3 days patients were discharged with no incidence of graft failure. The patients involved felt comfortable whilst remaining supine. We believe time saved by adequate protection leading to successful grafts makes this method economically useful. PMID- 1596670 TI - A method to ensure safer skin stapling. PMID- 1596671 TI - Reconstruction of the penis with a free deltoid flap. PMID- 1596672 TI - Actions of methoctramine, a muscarinic M2 receptor antagonist, on muscarinic and nicotinic cholinoceptors in guinea-pig airways in vivo and in vitro. AB - 1. The effects of the muscarinic M2 receptor antagonist methoctramine, on contractions of airway smooth muscle induced by cholinergic nerve stimulation and by exogenously applied acetylcholine (ACh), have been investigated in vivo and in vitro in guinea-pigs. 2. Stimulation of the preganglionic cervical vagus nerve in anaesthetized guinea-pigs, caused bronchoconstriction and bradycardia which were mimicked by an intravenous dose of ACh. The muscarinic M2 antagonist, methoctramine (7-240 nmol kg-1), inhibited the bradycardia induced by both vagal stimulation and ACh (ED50: 38 +/- 5 and 38 +/- 9 nmol kg-1, respectively). In this dose-range, methoctramine facilitated vagally-induced bronchoconstriction (ED50: 58 +/- 5 nmol kg-1), despite some inhibition of ACh-induced bronchoconstriction (ED50: 81 +/- 11 nmol kg-1). The inhibition of ACh-induced bronchoconstriction and hypotension was dose-dependent, but was not statistically significant until doses of 120 nmol kg-1 and 240 nmol kg-1 respectively. 3. In the guinea-pig isolated, innervated tracheal tube preparation, methoctramine (0.01-1 microM) caused facilitation of contractions induced by both pre- and postganglionic nerve stimulation, whereas contractions induced by exogenously applied ACh were unaffected. Higher concentrations of methoctramine (greater than or equal to 10 microM), reduced responses to both nerve stimulation and exogenous ACh, indicating blockade of post-junctional muscarinic M3 receptors. 4 ACh caused a slow maintained increase in tone of the tracheal tube and at the same time reduced the contractions induced by nerve stimulation. This inhibitory effect of ACh on neuronally mediated responses was antagonized by methoctramine (0.01-1 microM) in a concentration-dependent manner. However, the ACh-induced tone change was unaffected by methoctramine in this concentration-range, indicating a lack of muscarinic M3 receptor antagonist activity in this concentration-range.5. The effect of methoctramine on responses induced by pre- and postganglionic nerve stimulation was not identical. At concentrations of methoctramine of 1 ,microM and greater, preganglionic stimulation-induced contractions were reduced when compared to those induced by postganglionic stimulation, suggesting an inhibitory effect of methoctramine on ganglionic transmission. This ganglion blocking action of methoctramine was not due to its reported M1 receptor antagonist activity (blocking facilitatory Ml receptors in the ganglia) since pirenzepine was without effect in this preparation. We believe that the ganglionic blocking action of metoctramine is due to its nicotinic receptor antagonist properties, since the concentration of methoctramine inhibiting ganglionic transmission in the tube preparation (1 microM) was shown to inhibit contractions induced by the nicotinic agonist, 1,1-dimethyl-4-phenyl-piperazine in tracheal strips.6. These results show that methoctramine is able to demonstrate adequately the presence of autoinhibitory receptors functionally both in vivo and in vitro and confirms their pre-junctional location on pulmonary cholinergic nerve terminals and their classification as muscarinic M2 subtypes. These results also indicate that while methoctramine is a potent muscarinic M2 receptor antagonist, it does not possess the required selectivity to discriminate between cholinoceptor subtypes in preparations, such as the airways, where mixed populations of muscarinic and nicotinic cholinoceptors exist. PMID- 1596673 TI - The role of nitric oxide in endothelial cell damage and its inhibition by glucocorticoids. AB - Incubation of vascular endothelial cells with S.typhosa endotoxin and interferon gamma caused a time- and concentration-dependent reduction in the viability of the cells. The cytotoxic effect was inhibited in a concentration-dependent manner by NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, and by the glucocorticoids dexamethasone and hydrocortisone, two inhibitors of the induction of NO synthase. These findings indicate that in these cells the cytotoxic effect of endotoxin is mediated by the NO synthesized by an inducible NO synthase. This induction of NO synthase in vascular endothelial cells may represent a mechanism of local endothelial damage during endotoxin shock and other immunologically based conditions. PMID- 1596675 TI - Endothelin-1-induced [3H]-inositol phosphate accumulation in rat trachea. AB - 1. The effects of endothelin-1 (ET-1) and of the muscarinic cholinoceptor agonist, carbachol, on [3H]-inositol phosphate ([3H]-InsP) accumulation and smooth muscle contraction were determined in rat isolated tracheal tissue. 2. ET 1 (1 microM) and carbachol (10 microM) induced significant accumulation of [3H] InsPs in myo-[2-3H]-inositol-loaded rat tracheal segments. Several components of the tracheal wall including the airway smooth muscle band, the cartilaginous region and the intercartilaginous region generated significant levels of [3H] InsPs in response to ET-1 and carbachol. Following stimulation with ET-1, a greater proportion of tracheal [3H]-InsPs were generated in the intercartilaginous region (49%) than in either the airway smooth muscle band (25%) or cartilaginous region (26%). However, when the respective weights of these regions is taken into account, ET-1-induced accumulation of [3H]-InsPs was greatest in the airway smooth muscle band. The tracheal epithelium did not appear to generate [3H]-InsPs in response to ET-1 or modulate either basal or ET-1 induced accumulation of [3H]-InsPs in rat tracheal segments. 3. In the rat tracheal smooth muscle band, ET-1 caused a time- and concentration-dependent accumulation of [3H]-InsPs. Concentrations of ET-1 as low as 10 nM produced significant accumulation of [3H]-InsPs (1.23 +/- 0.10 fold increase above basal levels of 295 +/- 2 d.p.m. mg-1 wet wt., n = 3 experiments). At 10 microM, the highest concentration ?tsed, ET-1 produced similar levels of [3H]-InsP accumulation (7.03 +/- 0.55 fold above basal levels, t = 5) to that produced by a maximally effective concentration of carbachol (10 microM; 7.97 +/- 0.31 fold increase above basal levels, n = 4). ET-1-induced accumulation of [3H]-InsPs was not significantly affected by indomethacin (5 microM), nordihydroguaiaretic acid (NDGA, 10 microM), WEB 2086 (10 microM) or phosphoramidon (10 microM).4. ET-1 also produced concentration-dependent contractions of epithelium-denuded rat tracheal ring preparations. The mean concentration of ET-1 producing 50% of the maximum contractile response to carbachol (EC50) was 31 nm (95% confidence limits, 20-49 nM, n = 12). The presence of an intact tracheal epithelium, indomethacin (5 microM), WEB 2086 (10 microM) and phosphoramidon (10 microM) had no significant effect on the mean EC50 for ET-1-induced contraction (n = 5). In contrast, NDGA (10 microM) inhibited ET-1- induced contractions (4.0 fold increase in mean EC50, P < 0.001, n = 5). However, this effect of NDGA did not appear to be related to inhibition of leukotriene synthesis via lipoxygenase since the leukotriene antagonist SKF 104353 did not affect ET-1-induced contractions (n = 5) and moreover, leukotriene C4 and leukotriene D4 did not contract rat isolated tracheal smooth muscle preparations (n = 4).5. The threshold concentrations of ET-1 that produced increases in smooth muscle contraction and [3H]-InsPs accumulation were similar, although the EC50 for [3H] InsP accumulation was 2.9 fold greater than that for smooth muscle contraction. For carbachol, the EC50 for [3H]-InsP accumulation (mean ECQO = 5.0 microM, 1.2 21 microM, n = 4) was 25 fold greater than that for smooth muscle contraction(mean EC50 = 0.20 miicroM, 0.17-0.24 microM, n = 12).6. It seems likely that ET-1 has a direct effect on InsP generation in rat tracheal smooth muscle and that this is largely responsible for the spasmogenic actions of this peptide. PMID- 1596674 TI - The role of platelet-activating factor and peptidoleukotrienes in the vascular changes of rat passive anaphylaxis. AB - 1. The role of platelet-activating factor (PAF) and peptidoleukotrienes as putative mediators of some of the vascular changes triggered by antigen was investigated in rats passively sensitized with monoclonal anti-DNP (2,4 dinitrophenyl) IgE. 2. Lethal anaphylaxis with respiratory distress, systemic hypotension, detachment of the intestinal mucosa, leukopenia and extravasation of protein-rich plasma was observed after antigen challenge of rats sensitized with partially purified monoclonal IgE at concentrations of 15 mg protein kg-1. 3. Analysis of the peritoneal fluid obtained after i.v. challenge with DNP-BSA (bovine serum albumin) showed the presence of significant amounts of PAF (101 +/- 8 pg/rat), whereas this mediator was undetectable in control animals. Leukotriene D4 was the predominant peptidoleukotriene that could be recovered after antigen challenge, and showed an extremely high concentration (92 +2- 15 ng/rat) as compared to PAF levels. 4. Extravasation of protein-rich plasma was observed shortly after challenge and reached a maximum at 30 min. Treatment of animals with i.v. PCA 4248 (1-2 mg kg-1) and WEB 2086 (1 mg kg-1), two chemically unrelated compounds which are antagonists of the PAF-receptor, produced a significant reduction of the extravasation of protein-rich plasma. 5. The same degree of protection could be afforded by MK-886, an inhibitor of leukotriene biosynthesis. Combined treatment with WEB 2086 and MK-886 provided greater inhibition of protein-rich plasma extravasation than either compound alone. PCA 4248 was also found to inhibit in a dose-dependent manner the systemic hypotension observed upon DNP-BSA challenge.6. These data indicate that the lipid mediators PAF and peptidoleukotrienes are major effectors of the vascular disturbances observed in rat passive IgE-mediated anaphylaxis. PMID- 1596676 TI - Interaction of the central analgesic, tramadol, with the uptake and release of 5 hydroxytryptamine in the rat brain in vitro. AB - 1. Tramadol is a centrally acting analgesic with low opioid receptor affinity and therefore presumably other mechanisms of analgesic action. Tramadol inhibits noradrenaline uptake but since 5-hydroxytryptamine (5-HT) is also involved in the modulation of pain perception, we tested the effects of tramadol on 5-HT uptake and release in vitro. 2. Tramadol inhibited the uptake of [3H]-5-HT into purified rat frontal cortex synaptosomes with an IC50 of 3.1 microM. The (+)-enantiomer was about four times more potent than the (-)-enantiomer; the main metabolite of tramadol, O-desmethyltramadol, was about ten times less potent. 3. Rat frontal cortex slices were preincubated with [3H]-5-HT, then superfused and stimulated electrically. Tramadol facilitated the basal outflow of [3H]-5-HT, at concentrations greater than 1 microM, while the uptake inhibitor 5-nitroquipazine enhanced both basal and stimulation-evoked overflow. Effects of the (+) enantiomer were more potent than either the racemate, the (-)-enantiomer or the principal metabolite. 4. The effects of tramadol on the basal outflow of [3H]-5 HT were almost completely abolished when the superfusion medium contained a high concentration of the selective 5-HT uptake blocker, 6-nitroquipazine. 5. The results provide evidence for an interaction of tramadol with the neuronal 5-HT transporter. An intact uptake system is necessary for the enhancement of extraneuronal 5-HT concentrations by tramadol indicating an intraneuronal site of action. PMID- 1596677 TI - Responses to vasodilator drugs on pulmonary artery preparations from pulmonary hypertensive rats. AB - 1. Relaxant responses to six vasodilator drugs, with different mechanisms of action, were examined on noradrenaline (0.1 microM)-contracted ring preparations of pulmonary artery and aorta taken from rats with pulmonary hypertension induced by monocrotaline or chronic hypoxia. 2. On pulmonary artery preparations from monocrotaline-treated rats, compared with controls, (a) the maximum relaxation to pinacidil and cromakalim was significantly increased, but their potency (negative log EC50) was unchanged, (b) the potencies of nitroprusside and sodium nitrite were significantly reduced (10 fold and 3 fold respectively), but there was no change in the maxima, (c) for nicorandil there was an increase in maximum relaxation and a decrease in potency (3 fold), and (d) for atriopeptin II there was no change in potency or maximum. 3. The increase in maximum relaxation for pinacidil and the decrease in potency for nitroprusside were also demonstrated in pulmonary artery preparations from rats with chronic hypoxic pulmonary hypertension. The other four drugs were not examined in preparations from hypoxic rats. 4. In both models of pulmonary hypertension, no change in maximum response or potency was seen on aortic preparations for any of the vasodilator drugs. 5. In control preparations, none of the drugs was more potent on pulmonary artery than on aorta (i.e. they were not pulmonary-selective). In preparations from pulmonary hypertensive rats, pinacidil was selective for pulmonary artery, in contrast to nitroprusside which was selective for aorta.6. It is concluded that the development of pulmonary hypertension in rats is accompanied by changes in the responsiveness of the pulmonary arteries to some vasodilator drugs; whether or not these changes occur depends on the mechanism of action of the vasodilator drug, but they are independent of the method of inducing pulmonary hypertension.7. It is postulated that the reduction in potency seen for nitroprusside, sodium nitrite and nicorandil may be due to desensitization of soluble guanylate cyclase in pulmonary vascular smooth muscle in pulmonary hypertension. PMID- 1596678 TI - Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation. AB - 1. The effects of depletion of sensory neuropeptides from primary afferent neurones by capsaicin pretreatment, on the changes in resting gastric mucosal blood flow following administration of inhibitors of nitric oxide biosynthesis have been investigated in the pentobarbitone-anaesthetized rat. 2. Bolus administration of the NO-synthase inhibitor, NG-nitro-L-arginine methyl ester (L NAME; 0.8-12.5 mg kg-1 i.v.), induced a dose-dependent increase in systemic arterial blood pressure (BP) and a reduction in resting mucosal blood flow, as determined by laser Doppler flowmetry. 3. Concurrent administration of L-arginine (300 mg kg-1 i.v.) attenuated the effects of L-NAME (6.25 mg kg-1) on resting mucosal blood flow and BP. The enantiomer, D-NAME (50 mg kg-1 i.v.), which does not inhibit NO biosynthesis, had no effect on either parameter. 4. The fall in mucosal blood flow induced by submaximal doses of L-NAME (0.8-3.2 mg kg-1) was substantially augmented in rats pretreated 2 weeks earlier with capsaicin. 5. The fall in resting mucosal blood flow induced by the less potent NO-synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA; 1.6-25 mg kg-1 i.v.) was likewise significantly augmented in capsaicin-pretreated rats. 6. Pretreatment (15 min) with indomethacin (5 mg kg-1 i.v.) did not augment further the microvascular actions of L-NAME or L-NMMA in capsaicin-pretreated rats, suggesting the lack of interaction of endogenous prostanoids with these other mediators in regulating local blood flow. The effects of L-NAME on BP were not altered by capsaicin and indomethacin administration.7. These findings indicate that endogenous sensory neuropeptides and NO can interact in the regulation of the gastric microcirculation. PMID- 1596679 TI - Changes in plasma catecholamine and neuropeptide Y levels after sympathetic activation in dogs. AB - 1. Plasma levels of noradrenaline (NA) and neuropeptide Y (NPY) were evaluated in two experimental models associated with an increase in sympathetic tone: conscious dogs which were subject to either sinoaortic denervation or acute administration of the alpha 2-adrenoceptor antagonist yohimbine. 2. Dogs that had undergone sinoaortic denervation exhibited a two fold increase in plasma NA without any change in NPY levels. 3. Yohimbine (0.05 mg kg-1 i.v. as a bolus) produced similar effects. A higher dose of yohimbine (0.5 mg kg-1 i.v.) increased both plasma NA (7 fold) and NPY (6.5 fold) levels. 4. The present results indicate that changes in plasma catecholamines and NPY are not always concomitant. They suggest that the simultaneous release of NA and NPY is only observed under in vivo conditions for a marked increase in sympathetic tone. PMID- 1596680 TI - Effects of inhibiting nitric oxide biosynthesis on the systemic and splanchnic circulation of rats with portal hypertension. AB - 1. The effects of inhibiting endogenous nitric oxide (NO) synthesis with NG monomethyl-L-arginine (L-NMMA) on the systemic and splanchnic circulation have been investigated in rats with experimental chronic portal hypertension, anaesthetized with ketamine. 2. Portal hypertension was induced by partial portal vein ligation, 2 weeks prior to study. This procedure induced a reduction in systemic arterial blood pressure (MAP), an increase in cardiac output as measured by radiolabelled microspheres, a reduction in peripheral and splanchnic vascular resistance and an increased portal venous inflow (PVI) and portal pressure, as compared to control non-ligated rats. 3. L-NMAA (6.25 and 50 mg kg-1, i.v.) dose dependently increased MAP, reduced cardiac output and PVI, and increased peripheral and splanchnic vascular resistance. With L-NMMA (50 mg kg-1), PVI and the vascular resistances returned to values comparable to those determined in control non-ligated anaesthetized rats under resting conditions. 4. Porto collateral resistance was also increased by these doses of L-NMMA, whereas portal pressure was unchanged. The increase in renal blood flow and decrease in renal vascular resistance also seen in portal-hypertensive rats was reversed by L-NMMA (50 mg kg-1). 5. These effects of L-NMMA (50 mg kg-1) were inhibited by prior administration of L-arginine (300 mg kg-1, i.v.). 6. These findings indicate that the chronic hyperdynamic circulatory characteristics following portal vein stenosis can be attenuated by L-NMMA. Thus, the excessive formation of endogenous NO may be implicated in the pathogenesis of the haemodynamic disturbances and splanchnic vasodilatation associated with chronic portal hypertension. PMID- 1596681 TI - Effect of murine recombinant interleukin-5 on the cell population in guinea-pig airways. AB - 1. An intratracheal injection of murine recombinant interleukin 5 (mrIL-5, 2-15 microgram/0.25 ml/animal) induced a dose-dependent increase in the number of macrophages, eosinophils, neutrophils and epithelial cells in the bronchoalveolar lavage fluid (BALF) of guinea-pigs 24 h after administration. Bovine serum albumin (15 micrograms/0.25 ml/animal), used as a reference material, did not cause any change of this type. 2. The intratracheal administration of mrIL-5 at a dose of 15 microgram showed a tendency to increase the number of these pulmonary inflammatory cells and epithelial cells in the BALF at 12 h with a significant increase observed at 24 h. 3. Prednisolone (20 mg kg-1, i.p.) inhibited the mrIL 5-induced increase in macrophages, eosinophils, neutrophils and epithelial cells. Ketotifen (2 mg kg-1, i.p.) reduced the mrIL-5-induced increase in the eosinophil, neutrophil and epithelial cell populations. The simultaneous injection of 2% disodium cromoglycate (DSCG) into the trachea prevented the mrIL 5-induced increase in the number of airway epithelial cells, without affecting changes in the other inflammatory leukocytes. 4. These results suggest that mrIL 5 is a potent inducer of lung inflammation, in terms of increased inflammatory leukocytes and epithelial cells in guinea-pig BALF. Prednisolone, DSCG and ketotifen are effective against mrIL-5-induced pulmonary inflammation, especially the desquamation of bronchial epithelial cells. PMID- 1596682 TI - Mechanisms contributing to the regional haemodynamic effects of neurotensin in conscious, unrestrained Long Evans rats. AB - 1. The regional haemodynamic effects of i.v. bolus doses of neurotensin (10-1000 ng) were assessed in conscious, unrestrained Long Evans rats chronically instrumented with miniaturized, pulsed Doppler probes. 2. Neurotensin caused increases in blood pressure, together with dose-related tachycardias and constrictions in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia elicited by the 1000 ng dose of neurotensin was preceded by a transient bradycardia. 3. In the presence of phentolamine, the pressor effect of neurotensin (1000 ng) was converted into a hypotensive effect, accompanied by reduced tachycardic and constrictor responses in the renal, superior mesenteric and hindquarters vascular beds. The tachycardia was not preceded by a bradycardia. 4. In the presence of phentolamine and propranolol, the pressor and bradycardic responses to neurotensin were unaffected, whereas the tachycardia was abolished. The renal vasconstrictor effect was smaller, while the constrictions in the superior mesenteric and hindquarters vascular beds were not different from those in untreated rats. 5. In rats neonatally treated with capsaicin (50 mg kg 1, s.c.), the pressor effects elicited by neurotensin (300 and 1000 ng) were reduced as were the constrictor responses in the renal (at the dose of 300 ng), superior mesenteric (at the dose of 300 ng) and hindquarters (at both doses) vascular beds. The bradycardia elicited by neurotensin (1000 ng) was absent, whereas the tachycardia was potentiated. 6. The results indicate that in conscious, intact rats neurotensin appears to exert cardiovascular influences through activation of sympathoadrenal mechanisms and also through non-adrenergic effects on the heart, renal, superior mesenteric and hindquarters vascular beds. The latter effects appear to involve capsaicin-sensitive nerves. PMID- 1596683 TI - Mechanisms of coronary vasodilatation produced by ATP in guinea-pig isolated perfused heart. AB - 1. Isolated hearts of guinea-pigs were perfused in vitro with a physiological salt solution via a retrograde aortic cannulation (Langendorff preparation) at constant perfusion pressure. Bolus intra-arterial injections of various vasodilator drugs were made and the coronary flow responses were measured with an electromagnetic flow probe placed in the arterial inflow circuit. Inhibitory drugs were infused intra-arterially. 2. Nitro-L-arginine (NLA; 500 microM), an NO synthesis inhibitor, decreased coronary baseline flow by 16 +/- 0.8%, converted acetylcholine-induced coronary vasodilatation to vasoconstriction and had no effect on coronary flow responses to adenosine or papaverine. Sodium nitroprusside-induced responses were enhanced during NLA infusion by 46 +/- 11%. 3. Adenosine 5'-triphosphate (ATP) increased coronary flow but coronary flow responses to ATP were not altered by infusion of NLA. 4. ATP-induced coronary dilatation was not significantly attenuated by infusion of the adenosine receptor antagonist XAC, (xanthine amine congener; 2 microM), whereas XAC decreased coronary flow responses to adenosine by 75% +/- 5%. 5. ATP-induced coronary flow responses were reduced by only 31 +/- 4% during indomethacin infusion (2.8 microM) whereas indomethacin completely eliminated the initial vasoconstriction phase and greatly attenuated the peak flow and duration of the later vasodilatation phase seen in response to arachidonic acid (0.75 nmol). Indomethacin had no effect on vasodilatations produced by adenosine or prostaglandin I2. 6. These results indicate that ATP-induced coronary dilatation in the isolated, perfused heart of the guinea-pig is not dependent upon NO production or upon degradation of ATP to adenosine. The coronary dilator action of ATP may be partially dependent (approximately 30%) upon the production of vasodilator prostaglandins. PMID- 1596684 TI - Oxidative modification of low-density lipoproteins and the inhibition of relaxations mediated by endothelium-derived nitric oxide in rabbit aorta. AB - 1. The mechanism by which Cu(2+)-oxidized low-density lipoproteins (oxLDL) inhibit acetylcholine (ACh)-evoked relaxations mediated by endothelium-derived nitric oxide (EDRF) in rabbit aortic rings was investigated. The proposed role of lysophosphatidylcholine (LPC) in the inhibition was also studied. 2. The kinetics of lipid peroxidation of native low-density lipoproteins (LDL) from individual donors, as measured by changes in conjugated diene concentration, were related to the inhibitory effects of the resultant oxLDL. It was found that the more susceptible LDL was to oxidation, the greater the inhibition. 3. No correlation was found between the inhibitory effects of oxLDL and LPC content. 4. Synthetic 1 palmitoyl LPC produced an inhibition of ACh-induced relaxations and when added to precontracted rings evoked nitric oxide-mediated endothelium-dependent relaxation. This latter effect was not elicited by oxLDL. 5. Synthetic 1 palmitoyl (10 microM) had no effect on relaxations evoked by glyceryl trinitrate in endothelium-denuded aortic rings in contrast to the inhibition found previously for oxLDL. 6. Concentrations of oxLDL and phospholipase A2-treated LDL which inhibited relaxation contained very different LPC concentrations. Unlike oxLDL, the inhibitory effects of phospholipase A2-treated LDL preparations were independent of the donors and showed no lag period. 7. We suggest that there are differences in the mechanisms by which oxLDL and 1-palmitoyl LPC exert their inhibitory effects on relaxation. 8. The inhibition of relaxation by oxLDL (1-2 mg protein ml-1) was prevented by the presence of high-density lipoproteins (HDL; 1-2 mg protein ml-1).9. It is proposed that prevention of the inhibition of relaxation by HDL is consistent with the inhibitory factor(s) being lipophilic constituents of oxLDL. However, variations in the inhibitory effects of oxLDL preparations are not due to differences in their LPC content and factors other than LPC must contribute to the inhibition. PMID- 1596686 TI - PAF-induced muscarinic cholinoceptor hyperresponsiveness of ferret tracheal smooth muscle and gland secretion in vitro. AB - 1. The effects of exposure of the ferret trachea in vitro to platelet activating factor (PAF) were examined on methacholine-induced smooth muscle contraction, mucus volume and lysozyme outputs, and albumin transport across the tracheal epithelium. 2. Methacholine (0.1-30 microM) produced concentration-dependent increases in tracheal smooth muscle tone and mucus volume, lysozyme and albumin outputs from the trachea. 3. The concentration-response curves for methacholine induced smooth muscle contraction, mucus volume and lysozyme outputs were all shifted upwards after exposure of the trachea to PAF (1 microM) with a significant increase in maximum response for each variable. The EC50 values for methacholine-induced smooth muscle contraction and mucus volume output were significantly reduced after PAF exposure suggesting an increase in the potency of methacholine. The concentration-response curve for methacholine-induced albumin output was shifted downwards after PAF exposure with a greatly reduced maximum but no change in the EC50 for methacholine. 4. PAF-induced hyperresponsiveness of methacholine-induced smooth muscle contraction, mucus volume and lysozyme outputs was not affected by indomethacin, FPL55712, or mepyramine and cimetidine, but was prevented by catalase and superoxide dismutase (SOD), and by WEB2086. Similarly, PAF-induced inhibition of methacholine-stimulated albumin output was prevented by catalase and SOD, and by WEB2086. 5. We conclude that PAF induces hyperresponsiveness of ferret tracheal smooth muscle and submucosal gland secretion (including lysozyme secretion from serous cells) to methacholine. This hyperresponsiveness is probably produced by receptor-mediated release of oxygen free-radicals. The inhibition of methacholine-induced albumin flux suggests a loss of epithelial function which is also probably mediated by release of free radicals. The mechanism by which the free-radicals produce the changes in responsiveness to methacholine, and the cellular source of the free-radicals, remain to be established. PMID- 1596685 TI - Platelet-activating factor relaxes ferret tracheal smooth muscle and reduces transepithelial potential difference in vitro. AB - 1. The effects of platelet activating factor (PAF) were examined on the smooth muscle tone, mucus volume, lysozyme and albumin outputs and potential difference (PD) across the ferret tracheal wall. 2. PAF (0.1-10 microM) had no direct effect on mucus volume, lysozyme or albumin output from the ferret trachea. PAF produced concentration-dependent relaxations of the tracheal smooth muscle and reductions in PD across the tracheal wall. There was no change in the histological appearance of the trachea after exposure to PAF. 3. The PAF-induced smooth muscle relaxation was not affected by FPL55712, a combination of mepyramine and cimetidine, or by a combination of the oxygen free-radical scavengers catalase and superoxide dismutase (SOD); but was abolished by indomethacin or the PAF receptor antagonist WEB2086. 4. The PAF-induced reduction in PD was not affected by indomethacin, FPL55712 or mepyramine and cimetidine, but was prevented by catalase and SOD, and by WEB2086. 5. We conclude that PAF relaxes ferret tracheal smooth muscle in vitro by receptor-mediated release of a bronchodilator prostaglandin, possibly PGE2. PAF also reduces PD across the trachea suggesting changes in epithelial function; however, there is no histological epithelial damage after PAF. The reduction in PD with PAF is probably produced by receptor mediated release of oxygen free-radicals. The cellular source of these free radicals and of the dilator prostaglandin is unclear. PMID- 1596687 TI - Adenosine receptors in post-mortem human brain. AB - 1. Adenosine A2-like binding sites were characterized in post-mortem human brain membranes by examining several compounds for their ability to displace [3H]-CGS 21680 (2[p-(2 carboxyethyl)-phenethylamino]-5'-N-ethylcarboxamido adenosine) binding. 2. Two A2-like binding sites were identified in the striatum. 3. The more abundant striatal site was similar to the A2a receptor previously described in rat striatum, both in its pharmacological profile and striatal localization. 4. The less abundant striatal site had a pharmacological profile similar to that of the binding site characterized in the other brain regions examined. This was intermediate in character between A1 and A2 and may represent another adenosine receptor subtype. 5. The co-purification of [3H]-CGS 21680 binding during immunoisolation of human striatal cholinergic membranes was used to assess the possible cholinergic localization of A2-like binding sites in the human striatum. Only the more abundant striatal site co-purified with cholinergic membranes. This suggests that this A2a-like site is present on cholinergic neurones in the human striatum. PMID- 1596688 TI - Pharmacological characterization of RP 62203, a novel 5-hydroxytryptamine 5-HT2 receptor antagonist. AB - 1. RP 62203 (2-[3-(4-(4-fluorophenyl)-piperazinyl)propyl]naphto[1,8- ca]isothiazole-1,1-dioxide) is a novel naphtosultam derivative which shows very high affinity for 5-HT2 receptors in the rat cerebral cortex (Ki = 50.0 pM). 2. RP 62203 is relatively selective for this sub-type of 5-hydroxytryptamine (5-HT) receptor, having lower affinity for the 5-HT1A receptor and very low affinity for the 5-HT, receptor. RP 62203 displayed low to moderate affinity for alpha 1 adrenoceptors, dopamine D2 receptors and histamine H1 receptors. 3. In vivo binding experiments demonstrated that oral administration of low doses of RP 62203 led to a long-lasting (greater than 6 h) occupation of cortical 5-HT2 receptors (ID50 = 0.39 mgkg-1). 4. In cortical slices from the neonatal rat, RP 62203 potently inhibited inositol phosphate formation evoked by 5-HT, with an IC50 of 7.76 nM. 5. The activity of neurones in the raphe and their responses to microiontophoretically applied 5-HT were studied with extracellular recording electrodes in the anaesthetized rat. RP 62203 potently and dose-dependently blocked excitations evoked by 5-HT when administered at doses of 0.5-4.0 mg kg-1, i.p. In contrast, neither 5-HT-evoked depressions nor glutamate-evoked excitations of raphe neuronal firing were blocked by RP 62203 at doses as high as 8.0 mg kg-1, i.p. 6. Head twitches induced by 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane (DOI) could be abolished by low doses of RP 62203 in mice (ED50 = 0.44 mg kg-1, p.o.) and in rats (ED50 = 1.54 p.o.). Similar results were obtained with mescaline and 5-hydroxytryptophan (5-HTP). 7. The potency of RP 62203 was compared with that of three other 5-HT2 receptor antagonists, ritanserin, ICI 169,369 and ICI 170,809. In all models, RP 62203 showed similar activity to ritanserin, whilst either ICI 169,369 or ICI 170,809 was several fold less active. 8. It is concluded that RP 62203 is a potent and selective antagonist at 5-HT2 receptors in the rodent central nervous system. PMID- 1596689 TI - Changes in adrenoceptors and monoamine metabolism in neonatal and adult rat brain after postnatal exposure to the antihypertensive labetalol. AB - 1. The purpose of the present study was to investigate the acute (single injection), direct (chronic treatment) and the long-lasting effects after exposure to the alpha 1/beta-adrenoceptor antagonist labetalol during rat brain development on adrenoceptors and monoamine metabolism. 2. In 10-day-old rat pups, subcutaneously administered labetalol (10 mg kg-1) passed the blood-brain barrier, reaching a level of 2.1 micrograms g-1 tissue in the brain 90 min after injection. 3. Chronic labetalol treatment (10 mg kg-1, s.c., twice daily) during the first 10 days of life significantly increased alpha 1-adrenoceptor binding in the hypothalamus (+39%), but not in the occipital cortex. 4. This chronic postnatal labetalol treatment did not result in long-lasting changes in alpha 1- and beta-receptors measured on day 60. 5. A single labetalol injection (10 mg kg 1, s.c.) on postnatal day 10 significantly increased noradrenaline (NA) metabolism in all brain regions tested (+25 to 105%), but had no effects on 5 hydroxytryptamine (5-HT) or dopamine metabolism. 6. Chronic labetalol treatment between postnatal (PN) days 1 and 10 also increased NA metabolism on PN 10 (3 methoxy-4-hydroxyphenylglycol (MHPG)/NA, +20 to 100%), suggesting that tolerance to the acute effect of labetalol did not occur. A slight increase in 5-HT metabolism (20%) was induced by the chronic labetalol treatment in the hippocampus and meso-limbic system. 7. In general, long-lasting effects on NA metabolism could not be detected on day 60 more than one month after the treatment. However, 5-HT metabolism was significantly increased in all four brain regions measured (+20 to 70%). 8. We conclude that chronic labetalol exposure during early postnatal rat brain development does not cause long-lasting changes in beta-receptor number or NA metabolism, but appears to be critical for the rate of 5-HT metabolism in later life. PMID- 1596691 TI - Blockade by local anaesthetics of the single Ca(2+)-activated K+ channel in rat hippocampal neurones. AB - 1. Effects of local anaesthetics on single Ca(2+)-activated K+ channels were investigated using the inside-out configuration of the patch-clamp technique in single pyramidal neurones, which were freshly dissociated from rat hippocampus by use of proteolytic enzymes. 2. No significant effect was observed when 2 mM benzocaine was applied on either side of the membrane patch, or when 2 mM lignocaine or QX-314 was applied to the external surface of the membrane. 3. Lignocaine 1 mM, applied to the internal surface, slightly reduced the amplitude of the single K+ channel current. When applied to the internal surface QX-314 reduced the amplitude of the K+ channel current, accompanied by an increase in noise in the open channel current, suggesting a fast flickering block. The blocking effect of QX-314 on the outward current increased with depolarization, suggesting a binding site for the drug at an electrical distance of about 0.5 across the membrane field. 4. The open time histogram showed one exponential component and the closed time histogram showed at least two components. The mean open time of the outward current was increased when the amplitude was reduced by the drugs. 5. The ionized form of the local anaesthetics had a similar action on the Ca(2+)-activated K+ channels to that on Na+ channels, that is, they enter into the channel from the cytoplasmic side to induce open channel block. The blocking kinetics, however, might be so fast that they were beyond the frequency response of our recording apparatus, thus the recorded current amplitude was decreased. In contrast the K+ channel was not accessible via hydrophobic pathways for the neutral form, which is also known to block the sodium channel. PMID- 1596690 TI - Effect of milacemide on extracellular and tissue concentrations of dopamine and 5 hydroxytryptamine in rat frontal cortex. AB - 1. Milacemide is a glycine prodrug which is both an inhibitor and a substrate for monoamine oxidase-type B (MAO-B) and also an inhibitor of MAO-type A (MAO-A). Its effects on dopamine and 5-hydroxytryptamine (5-HT) metabolism in rat frontal cortex tissue and dialysate were evaluated. 2. Dialysate dopamine concentrations increased linearly and dose-dependently after milacemide administration (100, 200, 400 mg kg-1, i.p.), peaking at 1 h. A concomitant dose-dependent decrease in dialysate 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) concentrations was observed but these changes were smaller (27% and 40% respectively) than the change in dopamine (125% after 400 mg kg-1 milacemide). 3. Dialysate 5-HT was significantly increased only at 1.5 h after giving milacemide 400 mg kg-1. Dialysate 5-hydroxyindoleacetic acid (5-HIAA) concentration was not affected. 4. Milacemide (400 mg kg-1) at 1.5 h post-administration significantly increased frontal cortex tissue concentrations of dopamine and 5-HT; the percentage increase in dopamine being about four times that of 5-HT. Metabolite concentrations, including 5-HIAA, decreased. Changes in tissue and dialysate dopamine, DOPAC and HVA were approximately proportionate to each other. 5. The results are explicable in terms of an inhibition by milacemide of MAO-A. PMID- 1596692 TI - Platelet-activating factor synthesis by peritoneal mast cells and its inhibition by two quinoline-based compounds. AB - 1. Peritoneal mast cells from rat were co-incubated in vitro in a platelet aggregometer cuvette with washed rabbit platelets. In response to stimulation with calcium ionophore (A23187; 1-5 microM), the mast cells released a substance which stimulated the platelets to aggregate. These concentrations of ionophore did not stimulate platelet aggregation in the absence of mast cells, nor affect the responsiveness of the platelets to aggregation induced by thrombin or PAF. Release of a PAF-like substance was also observed in response to stimulation of the mast cells with antigen. 2. This pro-aggregatory activity is attributable to the release of PAF by the mast cells, since the activity could be abolished by preincubating the platelets with a specific PAF receptor antagonist (WEB 2086; 10 microM). Furthermore, the platelet-aggregating factor co-migrated with PAF on thin-layer chromatographs and could be abolished by incubation with phospholipase A2 (20 micrograms ml-1) or a specific antibody directed against PAF. 3. The release of PAF by peritoneal mast cells could be inhibited, in a concentration dependent manner, by PF-5901 (IC50 of 3.9 microM) or Wy-50,295 (IC50 of 1.2 microM), two structurally similar compounds with inhibitory effects on leukotriene synthesis, as well as leukotriene D4 (LTD4) receptor antagonist properties. 4. Inhibition of PAF synthesis was not observed when the mast cells were incubated with a structurally unrelated 5-lipoxygenase inhibitor (A-64077), a structurally dissimilar inhibitor of 5-lipoxygenase activating protein (MK-886) or with a structurally related LTD4 receptor antagonist (MK-571) which lacks inhibitory effects on leukotriene synthesis, each at concentrations of up to 100 microM.5. Neither PF-5901 nor Wy-50,295 (1 or 10 microM) significantly affected histamine release or prostaglandin D2 synthesis by peritoneal mast cells in response to calcium ionophore stimulation.6. These results demonstrate the ability of a class of quinoline-based compounds to inhibit PAF synthesis by peritoneal mast cells. This activity does not appear to be related to effects of these compounds on leukotriene synthesis or LTD4 receptors. The ability of these compounds to inhibit PAF synthesis may contribute to their anti-inflammatory properties. PMID- 1596693 TI - Inhibition of neuropeptide Y-induced potentiation of noradrenaline-induced vasoconstriction by PP56 (D-myo-inositol 1,2,6-tris-phosphate). AB - 1. Although neuropeptide Y (NPY) is a potent vasoconstrictor in many vascular beds, nanomolar concentrations of this peptide potentiate the noradrenaline induced contractions in rabbit gastroepiploic and femoral arteries, and guinea pig mesenteric and uterine arteries. 2. The potentiating effect of NPY on noradrenaline-induced contraction was present in endothelium-denuded femoral arteries. 3. The potentiating effect of NPY on noradrenaline-induced contraction was antagonized by PP56 (D-myo-inositol 1,2,6-trisphosphate) in low concentrations (down to 0.1 nM). This antagonistic effect was observed in all four types of vessels studied. Contractions induced by noradrenaline, histamine, endothelin-1 and potassium were not altered by PP56 in concentrations upto 1 microM in femoral artery of rabbit. 4. We provide evidence that a non-peptide (PP56) can selectively antagonize NPY-induced effects in rabbit and guinea-pig peripheral arteries without affecting the vasoconstrictor response to noradrenaline. PMID- 1596695 TI - The new national health service, trusts and rheumatology. PMID- 1596696 TI - British health professionals in rheumatology. PMID- 1596694 TI - Binding properties of nine 4-diphenyl-acetoxy-N-methyl-piperidine (4-DAMP) analogues to M1, M2, M3 and putative M4 muscarinic receptor subtypes. AB - 1. We compared the binding properties of 4-diphenyl-acetoxy-N-methyl-piperidine methiodide (4-DAMP) and nine analogues of this compound on muscarinic receptors of human neuroblastoma NB-OK1 cells (M1 subtype), rat heart (M2 subtype), rat pancreas (M3 subtype) and to the putative M4 subtype in striatum. 2. The requirements for high affinity binding were somewhat different for the four receptor subtypes. In general, the requirements of M3 receptors were more stringent than for M1, M2 or putative M4 receptors. 3. The abilities of the compounds to discriminate muscarinic receptor subtypes were not correlated with their affinities at any subtype. 4. The temperature-dependence of binding of 4 DAMP analogues to M2 receptors varied with the drug structure. In particular, the increased affinity of the alpha-methyl derivative of 4-DAMP could be ascribed to van der Waals interactions. 5. The affinities of most 4-DAMP analogues for M2 and M3 receptors were similar to their pharmacological potencies on atrial and ileum preparations, respectively. 6. At concentrations above 1 microM, all 4-DAMP analogues as well as atropine, reduced the [3H]-N-methyl scopolamine ([3H]-NMS) dissociation rate from cardiac muscarinic receptors, with no obvious structure activity relationship. PMID- 1596697 TI - Incidence of rheumatoid arthritis in a genetically predisposed population. AB - A follow-up study (mean duration five years) was undertaken on 370 previously unaffected first degree relatives from multicase rheumatoid arthritis (RA) families. The objectives were to determine the incidence of RA in this group and the possible predictors of disease development. In all, 14 individuals developed RA, equivalent to an incidence of 8/1000 person-years of observation. There was no control group included in this study as the intensive-follow-up required substantial compliance from highly motivated families. Population-based estimates, however, from a number of sources would suggest an annual incidence below 0.5/1000 per year, substantially less than the rate obtained in this study. The small number of incident cases precluded definitive conclusions about risk factors within these families but there were no important effects of age or sex. Possession of HLA-DR1 or DR4 explained only some of the increased risk. The increased incidence observed in the previously unaffected relatives of such families would suggest that this familial clustering did not for the most part arise by chance and that other shared genetic or environmental influences are relevant. PMID- 1596698 TI - Susceptibility of normal and arthritic human articular cartilage to degradative stimuli. AB - Recombinant interleukin-1 (IL-1) alpha and beta stimulated significant loss of glycosaminoglcan (GAG) content from normal (non-arthritic) articular cartilage explants but only after incubation for 14 days and only in specimens from 8/21 (38%) individuals. By contrast, all cartilage specimens but one from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were degraded (as judged by their reduced GAG content) by the recombinant cytokines but again only after 14 days' incubation. The reduction in GAG induced by IL-1 was also greater for both OA and RA cartilage than normal cartilage. Synovial fluids (SFs) from RA patients stimulated greater loss of GAG content from OA cartilage explants than normal explants although in both cases the loss was evident within 2 days. It is concluded that cartilage explants from some individuals are susceptible to the degradative effects of IL-1 whereas others are refractory and that arthritic cartilage is more susceptible to degradation by both IL-1 and RA SFs than non arthritic cartilage. PMID- 1596700 TI - Septic bone, joint and muscle lesions associated with human immunodeficiency virus infection. AB - Ten episodes of musculoskeletal sepsis have been seen in nine patients with HIV infection. Seven patients had AIDS, circulating CD4-positive lymphocyte counts being less than 0.1 x 10(9)/l in six. Septic arthritis recurred in seven patients, osteomyelitis in three and pyomyositis and bursitis each occurred in one patient. Staphylococcus aureus was isolated from four patients, atypical micro-organisms being found in three. Presentation of musculoskeletal infection in this patient group may be atypical but rapid diagnosis is important as early antimicrobial therapy is often successful. PMID- 1596699 TI - Further evidence of increased polymorphonuclear cell activity in patients with Raynaud's phenomenon. AB - The role of polymorphonuclear cells (PMNs) in the pathophysiology of ischaemic vascular disease has been increasingly recognized in recent years. Activated PMNs may physically obstruct blood flow. Subsequent release of reactive oxygen radicals and lytic enzymes lead to continued damage. Previous studies have shown increased white cell activity in patients with secondary Raynaud's syndrome (RS). However, whether this is related to the underlying condition or to digital vasospasm is not clear. Using a more physiological whole blood PMN aggregation assay, we assessed PMN activity in 38 patients with severe Raynaud's phenomenon (RP) [16 had systemic sclerosis (SSc) and secondary RS; 22 had RP alone and no other features of a connective tissue disease]. Additionally, plasma levels of malondialdehyde (MDA), an indicator of free radical activity, were measured. Results were compared with those obtained from 56 matched volunteers. In order to assess if changes in PMN activity was directly related to digital vasospasm, patients were asked to record the duration and frequency of their Raynaud's attacks during a 2-week period using a pocket sized diary. Correlation between these clinical variables of Raynaud's severity and white cell activity was assessed. Patients with RP, both with and without SSc, showed a significantly greater fall in single PMN count when compared with control subjects [SSc associated RS 48.2 (41.4-56)% versus control, P = 0.04; RP alone 49.3 (46.8 52.1)% versus control, P = 0.01 (Mann-Whitney U-test)].(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596701 TI - An examination of the role of female hormones and pregnancy as risk factors for rheumatoid arthritis, using a male population as control group. AB - While being female is known to increase the risk of developing rheumatoid arthritis approximately threefold, this study, by making use of a male control group, suggests that female sex hormones per se are unlikely to be the main cause of this discrepancy. Apart from the teens, when rheumatoid disease is extremely rare in males, the female/male incidence ratio remains almost constant throughout the adult age range, in spite of the reduction in endogenous oestrogen levels at the menopause. Pregnancy is known to ameliorate RA, but this study found that it was also the most common identifiable event preceding the onset of RA in women of childbearing age (22%), which may explain the apparent protective role of oral contraceptives in this age group. PMID- 1596702 TI - Lyme borreliosis: a very infrequent cause of arthritis of undetermined aetiology in the southern part of The Netherlands. AB - Seventy-three patients with undiagnosed arthritis of undetermined aetiology, 94 patients with classified arthritis (rheumatoid arthritis, ankylosing spondylitis, etc.) and 70 controls were studied for clinical and serological manifestations of Lyme borreliosis. The patients were recruited from the three rheumatology units in the most southern part of The Netherlands. A clinical diagnosis of possible Lyme borreliosis was made in seven of 73 patients with arthritis of undetermined aetiology, in four of 94 patients with classified arthritis and in one of the controls. A definite diagnosis of Lyme borreliosis could be made in only one patient who belonged to the arthritis of undetermined aetiology group. This patient had erythema migrans, arthritis of the knee joint and showed positive antibodies to B. burgdorferi. In the southern part of The Netherlands, Lyme arthritis does not seem to be a frequent cause of arthritis of undetermined aetiology. PMID- 1596703 TI - A preliminary study on the effect of alpha-interferon treatment on the joint inflammation and serum calcium in rheumatoid arthritis. AB - A 12-week, double-blind controlled study comparing low dose alpha-interferon (5 x 10(5) iu, twice a week) and placebo was carried out to determine whether this drug has an immunomodulatory effect in rheumatoid arthritis. There were statistically significant improvements in the patients' joint score, C-reactive protein value and platelet count, without any side effects. Interferon-alpha caused an increase of serum calcium and a decrease of alkaline phosphatase. Thus, alpha-interferon requires further investigation as a possible additional useful treatment for rheumatoid arthritis. PMID- 1596704 TI - Guidelines on undergraduate curriculum in the UK. Education Committees of Arthritis and Rheumatism Council and British Society for Rheumatology. AB - Symptomatic locomotor abnormalities are common in medical in-patients, form a significant part of a general practitioner's workload, and are the single most important factor influencing disability in later life. That any qualifying doctor should have basic competencies with respect to the locomotor system thus seems appropriate. A survey of medical schools undertaken jointly by the Arthritis and Rheumatism Council (ARC) and British Society for Rheumatology (BSR) in 1990, however, suggests that the locomotor system still has a relatively low priority in undergraduate medical training. In 1990 therefore, the Education Committees of ARC and BSR established a joint working party to define guidelines on an undergraduate curriculum for rheumatology. These guidelines were discussed and developed at a Workshop in Oxford, and circulated to the Deans and Chairmen of Curriculum Committees at all UK Medical Schools in October 1991. It is hoped these guidelines will encourage inclusion of basic rheumatological competencies within the 'core' curriculum for all medical undergraduates. PMID- 1596705 TI - Costovertebral joint changes in ankylosing spondylitis with thoracic pain. AB - CAT scan of the costovertebral joints has been performed in 17 patients with ankylosing spondylitis, all suffering from lower thoracic pain. Fourteen of them (82%) showed abnormal findings, including erosions and sclerosis, more pronounced in the vertebral side of the joint, and joint widening. Bony proliferation arising from the vertebral side in the anterior margin of the joint was also seen. One patient showed at the D12 level anterior bony bridges, similar to the vertebral syndesmophytes. Fusion was noted in five patients (including the three with longest disease duration) and represents the end result of the inflammatory process. These changes provide an anatomical basis for the understanding of the thoracic pain in AS patients. PMID- 1596706 TI - Adult-onset Still's disease in India. AB - Adult onset Still's disease was provisionally diagnosed in 31 patients from northern India over a period of five years, in 27 of whom the diagnosis was subsequently felt to have been confirmed. This report describes the clinical characteristics of these patients along with the different therapeutic measures used and their response. Adult onset Still's disease should be considered in the differential diagnosis of 'pyrexia of unknown origin'. PMID- 1596707 TI - Tophaceous pyrophosphate deposition with extensor tendon rupture. AB - Tophaceous deposition of calcium pyrophosphate dihydrate (CPPD) crystals is considered unusual as is deposition within tendon sheaths. Associated tendon rupture is described but is rare. We report a lady with tophaceous CPPD deposition at the wrist, a previously unreported site. Contrary to previous cases, this occurred in the setting of symptomatic, polyarticular, pyrophosphate arthropathy. An additional point of interest was development of associated extensor tendon rupture with features favouring a non-inflammatory mechanism of tendon damage. PMID- 1596708 TI - Methotrexate associated Peyronie's disease in the treatment of rheumatoid arthritis. AB - We describe two patients with rheumatoid arthritis treated with methotrexate (MTX) who developed Peyronie's disease during the course of their treatment. In one of the patients the penile fibrosis resolved on stopping the drug. The other patient's penile fibrosis partially resolved on stopping the drug. We suggest that Peyronie's disease can be a side-effect of MTX in the treatment of rheumatoid arthritis. PMID- 1596709 TI - Spinal cord compression revealing a destructive arthropathy of the atlanto occipital joint associated with beta-2 microglobulin amyloidosis in a haemodialysed patient. PMID- 1596710 TI - Successful treatment of gold-induced aplastic anaemia with granulocyte macrophage colony stimulating factor. PMID- 1596711 TI - Sjogren's syndrome and inflammatory bowel diseases. PMID- 1596712 TI - Steroid treatment in giant cell arteritis. PMID- 1596713 TI - Impotence. PMID- 1596714 TI - Autotransfusion with salvaged blood. PMID- 1596715 TI - Crohn's disease and nutrition. AB - Malnutrition was included by Crohn as one of the features of the new disease he described. Most patients with Crohn's disease are malnourished even if their disease is not active. Nutritional factors may be implicated in the aetiology of the disease, but this remains unproven. The role of nutritional support and therapy is discussed and it is suggested that improving the patient's nutritional status may have a primary therapeutic as well as a supportive role in the treatment of the disease. PMID- 1596716 TI - Assessment of quality of life in surgery. AB - The concept of patients' quality of life is assuming increasing importance in modern medicine and surgery. Interventions are increasingly being assessed in terms of their impact on such areas of functioning as mobility, mood, cognitive function, ability to fulfil occupational and social roles, and general life satisfaction. This paper discusses the theoretical underpinnings of the quality of-life paradigm and its practical relevance for modern surgery. PMID- 1596717 TI - Knotting technique and suture materials. AB - Three groups of knots were examined using six no. 1 (metric 4) suture materials to identify the most effective and efficient knotting techniques. The three groups were the square or reef knot, the surgeon's knot and a double throw knot. Sequential single additional throws were added to these in order to determine when the strength of the knot reached the breaking force of the material, thus nullifying the need for additional throws. This strength was reached in all cases by a maximum of two additional throws. Suture materials examined were the non absorbable monofilaments nylon and polypropylene, the absorbable monofilaments polyglyconate and polydioxanone and the braided materials polyglactin and polyglycolic acid, both coated. These were examined for their knot-holding capacity and breaking force to determine the best materials, which were polypropylene, polyglyconate and polyglycolic acid. PMID- 1596718 TI - Prediction of wound tensile strength: an experimental study. AB - Wound cell specimens were obtained using a Cellstic device after 24, 48 and 72 h healing time in guinea-pig skin wounds. Cell counts from these were compared with the tensile strength values of the same wounds 7, 14 or 21 days after operation. No single cell type was predictive of wound tensile strength, although absolute numbers of different cells and selected ratios of cell types on the second or third day after operation were more predictive. Absolute and proportional changes from day 1 to day 2 had the greatest predictive power with a mean error of 9.46 per cent (F = 13.6, P less than 0.0001). The same regression model was predictive in animals with lower wound tensile strengths given perioperative hydrocortisone (3 mg/100 g). PMID- 1596719 TI - Adenomatous goitre: therapeutic strategy, postoperative outcome, and study of epidermal growth factor receptor. AB - A total of 377 patients with histologically proven adenomatous goitre was operated on, 34 as a second operation, and assessed for postoperative outcome (including the incidence of unsuspected malignancy) and immunohistochemical localization of epidermal growth factor receptor. In primary surgery, enucleation of all the nodules was carried out. Patients requiring reoperation showed multicystic degenerate nodules involving one or both lobes. A coexistent cancer was observed in 18 patients (4.8 per cent). The immunohistochemically detected expression of epidermal growth factor receptor in adenomatous goitre was more evident in patients with multinodular lesions. Near-total lobectomy of the involved side(s) is desirable for the prevention of recurrence and complications after operation. PMID- 1596720 TI - Plasma fatty acid profiles in benign breast disorders. AB - Breast pain (mastalgia) and macroscopic breast cysts present commonly. Mastalgia may be improved by dietary manipulation to reduce saturated fat or supplement essential fatty acid intake. Fatty acid profiles were measured in women with mastalgia and breast cysts, before and during treatment with evening primrose oil, a rich source of essential fatty acids. The fatty acid profiles of both groups of patients were abnormal, with increased proportions of saturated fatty acids and reduced proportions of essential fatty acids. Treatment with evening primrose oil improved the fatty acid profiles towards normal, but this was not necessarily associated with a clinical response. PMID- 1596721 TI - Comparison of Nissen total and Lind partial transabdominal fundoplication in the treatment of gastro-oesophageal reflux. AB - Fifty-two patients with gastro-oesophageal reflux disease refractory to medical treatment were randomized to undergo a Nissen total (360 degrees wrap) or Lind partial (300 degrees wrap) transabdominal fundoplication. Each group was comparable in number (26 patients), mean age (47 and 48 years) and sex distribution (eight women). Preoperative and postoperative assessment involved a modified Visick score, 22-h intraoesophageal pH monitoring, endoscopy and manometry. Follow-up was at 6 weeks and between 3 and 33 (mean 13) months. The prevalence of heartburn and regurgitation and the results of pH monitoring improved significantly after both operations (P less than 0.001). At early assessment eight previously asymptomatic patients (31 per cent) from the Nissen group and six (23 per cent) from the Lind group experienced difficulty swallowing. Ten patients (38 per cent) in each group complained of 'gas bloat'. Both complications had improved at late assessment in the majority of patients. No statistically significant advantage could be demonstrated for either operation. PMID- 1596722 TI - Attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus. AB - A survey was carried out into attitudes of cardiothoracic surgeons in the UK to human immunodeficiency virus type 1 (HIV-1) infection associated with clinical situations that would normally have been managed surgically with low operative mortality rates and long median survival times. The survey response rate was 72.4 per cent. In patients with acute valvular insufficiency or with continuing angina despite maximal medical therapy (unstable angina) who were HIV-1 antibody positive, 75.8 and 80.8 per cent, respectively, of surgeons would operate. If the patient had end-stage infection, acquired immune deficiency syndrome (AIDS), 29.7 per cent and 34.7 per cent, respectively, would consider surgical intervention. When asked to perform simple procedures such as open lung biopsy or pleurectomy on a patient with AIDS, more than half of surgeons would operate (52.2 and 65.6 per cent respectively). In patients with operable carcinoma of the lung and asymptomatic HIV-1 infection 52.3 per cent would operate. This fell to 15.0 per cent if the patient had a diagnosis of AIDS. The majority of surgeons (77.2 per cent) felt patients should have an HIV-1 antibody test before operation and this rose to 95.6 per cent if patients were in a high-risk group; 60.2 per cent of surgeons had changed their surgical practice to reduce the risks of blood-borne infection. PMID- 1596723 TI - Bioelectrical impedance analysis in the measurement of the body composition of surgical patients. AB - The evaluation of nutritional status in surgical patients remains a difficult problem. Bioelectrical impedance analysis (BIA) is a new method of body composition analysis which is easily performed at the bedside. This study determined the accuracy of BIA in the measurement of total body water (TBW) and potassium (TBK) in a heterogeneous group of surgical patients. The resistance and reactance components of impedance were measured with a whole body impedance analyser. Tritiated water dilution and whole body monitoring were the reference methods for TBW and TBK analysis. With the BIA technique the coefficient of variation for the estimation of TBW was 8.1 per cent and for TBK was 6.4 per cent. Allowing for the errors of the reference methods these results show that BIA is of limited value in the estimation of TBW but may provide a useful index of TBK. PMID- 1596724 TI - Persistence of allogeneic cells in graft and host tissues after small bowel transplantation. AB - Small bowel transplantation is associated with a significant risk of graft versus host disease owing to the large amount of organized lymphoid tissue within the graft. This study assessed whether graft lymphoid cells could persist in the long term following fully allogeneic small bowel transplantation when graft rejection was prevented by cyclosporin immunosuppression. Transplantation was carried out between PVG and DA strains of rat. Cyclosporin (15 mg/kg) was given daily from transplantation, and groups of animals were studied at 28 and 56 days after grafting. The proportions of donor- and recipient-derived cells in the graft and in the host gut and lymphoid tissues were assessed using immunohistochemical tissue staining and monoclonal antibodies specific for cells expressing class I antigens from the two strains of rat. Results demonstrated a persisting population of graft-derived T cells which were capable of migration to the host. Therefore, there may be a long-term risk of graft versus host disease after small bowel transplantation under cyclosporin immunosuppression. PMID- 1596725 TI - Effect of phosphatidylcholine on postoperative adhesions after small bowel anastomosis in the rat. AB - The possibility of preventing postoperative adhesions using phosphatidylcholine (PC) was studied in rats. A small bowel anastomosis was created using continuous or interrupted 5/0 silk sutures. Adhesions were measured by recording the maximal length of adhesions around the anastomosis and the number of organs involved in the adhesions. PC was administered intraperitoneally either as a single dose or as three separate doses. Postoperative adhesions developed in all animals; the degree of adhesion was independent of the suture technique used. PC given once at a dose of 20 mg significantly decreased adhesion formation (P less than 0.01). The mechanism underlying this effect may be that the exogenous PC provides a lubricant layer replacing endogenous hydrolysed phospholipid. The result with repeated PC administration was not different from that after a single dose. Increasing the single dose of PC to 40 or 60 mg resulted in anastomotic dehiscence and subsequent peritonitis. It is concluded that PC in a single dose of 20 mg reduces adhesion formation after small bowel anastomosis in the rat. PMID- 1596726 TI - Audit of general practitioner referrals to an acute surgical unit. AB - One hundred and ninety referrals from general practitioners (GPs) to an acute surgical unit were audited prospectively over a 6-month period. A total of 78 admissions were considered inappropriate of whom 23 patients were thought to have needed neither surgical admission nor opinion. The estimated expenditure resulting from admissions deemed inappropriate was 25,000 pounds. The daytime commitments of more senior staff on routine emergency duty days meant they were not easily available to deal with calls concerning acute GP referrals. These admissions reduce the efficiency of the service; this may be improved by a senior member of the team accepting and screening GP calls. PMID- 1596727 TI - Management of colovesical fistulae associated with pelvic malignancy. AB - Thirteen patients with malignant colovesical fistulae are presented. The underlying pathology was cancer of the colon (seven cases), bladder (four cases) and cervix (two cases). The series demonstrates that wide surgical excision may be needed to achieve tumour clearance and that this may necessitate pelvic exenteration. Three patients who underwent inadequate tumour excision developed recurrence in the bladder, two with a fatal outcome. Wide excision of the bladder may be performed without urinary diversion by subtotal cystectomy and a reconstructive procedure. Substitution cystoplasty was performed on two patients at the time of tumour excision. Urinary tract involvement by such tumours is often extensive and optimal results may be achieved with a multidisciplinary approach. PMID- 1596728 TI - Outcome in patients with early colorectal carcinoma. AB - Twenty-four patients seen between 1978 and 1990 with early colorectal carcinoma were reviewed to determine the outcome of surgical treatment. The mean age was 62 (range 35-79) years; there were 16 men and eight women. The site of the tumour was the ascending colon in two patients, sigmoid colon in ten and rectum in 12. The polypoid and flat-elevated ulcerated (IIa+IIc) subtypes were detected in 14 and nine lesions respectively. Restorative colectomy was carried out in 19 patients, and five required Mile's operation. There were no postoperative complications or deaths at a mean follow-up of 71 (range 12-151) months. Neither recurrence nor distant metastasis was found during follow-up. There was a close relationship between the depth of submucosal invasion and presence of flat elevated ulcerated subtype lesions with lymphatic infiltration. This association may play an important role in the mechanism of metastasis. Major surgical resection is probably required if longer disease-free intervals and better cure rates are desired. PMID- 1596730 TI - The 75th meeting of the Surgical Research Society. 9-10 January 1992, England. Abstracts. PMID- 1596729 TI - Restoration of continence following rectopexy for rectal prolapse and recovery of the internal anal sphincter electromyogram. AB - Twenty-two patients with full-thickness rectal prolapse underwent ambulatory fine wire electromyography of the internal and sphincter (IAS), external and sphincter and puborectalis, together with anorectal manometry, using a computerized system. Examinations were performed both before and 3 to 4 months after rectopexy. The median (interquartile range (i.q.r.)) preoperative IAS electromyogram (EMG) frequency was 0.18 (0.05-0.31) Hz and the median (i.q.r.) preoperative resting anal pressure was 28 (15-64) cmH2O. An improvement in the IAS EMG frequency, median (i.q.r.) 0.29 (0.19-0.38) Hz (P less than 0.03), and resting anal pressure, median (i.q.r.) 41 (20-72) cmH2O (P less than 0.05), was recorded after operation, but these variables remained significantly lower than those found in normal controls: median (i.q.r.) IAS EMG frequency 0.44 (0.36-0.48) Hz and median (i.q.r.) resting anal pressure 92 (74-98) cmH2O. We suggest that repair of the prolapse allows the IAS to recover by removing the cause of persistent rectoanal inhibition. PMID- 1596731 TI - Pancreatic tissue and ductal pressures in chronic pancreatitis. PMID- 1596732 TI - Severe haemorrhagic complication following needle or open biopsy of a breast mass: suspect angiosarcoma. PMID- 1596733 TI - Use of a resorbable mesh graft to obtain haemostasis from the cut surface of the liver after hepatic resection. PMID- 1596734 TI - Medical audit: use of routine erect abdominal radiographs. PMID- 1596735 TI - Perioperative blood transfusion does not promote recurrence and death after mastectomy for breast cancer. PMID- 1596736 TI - Hippocampal auditory evoked response threshold in the rat: behavioral modulation. AB - Summed auditory evoked responses (AERs) were recorded bipolarly from CA1 field and inner molecular layer of the dentate gyrus of the hippocampus (Hipp) and compared to AERs simultaneously recorded from other extralemniscal (EL) nuclei and the inferior colliculus (IC) in the rat. There were no significant threshold differences for early Hipp AER (EHAER) and other EL AERs. The threshold for EHAERs and other EL AER was by several tens of decibels above that for IC, but usually lower than that for eliciting muscular reflexes. Actual behaviour (still waking, drowsiness, exploration, attention to stimuli) modified the thresholds for EHAER and other EL AERs equally. There was only little effect of actual behavior upon nonthreshold modulation of amplitudes of EHAERs. It is assumed that setting the threshold of the hypothetical common source of EH and other EL AERs plays main role in their behavioral modulation. As supposedly EHAERs are mediated through the perforant path, our results suggest that this pathway might transmit information related to high-threshold diffuse activation of the brain during the early stage of auditory processing. PMID- 1596737 TI - Opiate activation suppresses the drinking, pressor and natriuretic responses induced by cholinergic stimulation of the medial septal area. AB - The present study investigates the participation and interaction between cholinergic and opiate receptors of the medial septal area (MSA) in the regulation of Na+, K+ and water excretion, drinking and blood pressure regulation. Male Holtzman rats were implanted with stainless steel cannulae opening into the MSA. Na+, K+ and water excretion, water intake and blood pressure were measured after injection of carbachol (cholinergic agonist), FK 33824 (an opiate agonist) + carbachol or naloxone (an opiate antagonist) + carbachol into MSA. Carbachol (0.5 or 2.0 nmol) induced an increase in Na+ and K+ excretion, water intake and blood pressure and reduced the urinary volume. FK 33824 reduced the urinary volume and Na+ and K+ excretion. Previous injection of FK-33824 (100 ng) into the MSA blocked the increases in Na+ and K+ excretion, water intake and blood pressure induced by carbachol. Naloxone (10 micrograms) produced no changes in the effect of 2.0 nmol carbachol, but potentiated the natriuretic effect induced by 0.5 nmol dose of carbachol. These data show an inhibitory effect of opiate receptors on the changes in cardiovascular, fluid and electrolyte balance induced by cholinergic stimulation of the MSA in rats. PMID- 1596738 TI - Evidence for a different sensitivity to various central effects of interleukin-1 beta in mice. AB - Interleukin 1 (IL-1) induces a series of metabolic and endocrine effects. Activation of the hypothalamus-pituitary-adrenal axis, inhibition of food and water intake, elevation of serum interleukin-6 (IL-6) concentration and hypoglycemia are some of the effects induced by IL-1. The purpose of this study was to compare the sensitivity of these effects following central and peripheral administration of IL-1 beta. Different doses of IL-1 beta (0.1-1000 ng/mouse) were centrally (ICV) or peripherally (IP) injected to male mice two hours prior to sacrifice. The ICV administration was more efficacious than the IP injection in elevating serum corticosterone and IL-6 concentrations, whereas no difference was evident in the IL-1 beta-induced hypoglycemia. Central IL-1 beta administration was also more potent than IP injection in inhibiting overnight food and water intake. A dose-dependent effect was evident in all these cases. In summary, our data compare effects elicited by central or peripheral administration of different doses of IL-1 beta. This comparison suggests that the IL-1 beta stimulation of serum corticosterone and IL-6 and inhibition of food and water intake are events more centrally mediated than the IL-1 beta-induced hypoglycemia. PMID- 1596739 TI - Properties of ventrolateral medullary neurons that respond to muscular contraction. AB - Previous results from this laboratory have suggested that neurons in the ventrolateral medulla (VLM) modulate the pressor response to muscular contraction. The purpose of the present study was to determine 1) if VLM neurons with a discharge pattern related to sympathetic discharge and/or the cardiac cycle are stimulated during muscular contraction, 2) if the neurons activated by muscular contraction project to the intermediolateral columns of the spinal cord and 3) the location of glutamate immunoreactive neurons in the medulla. Single unit responses of ventrolateral medullary neurons to hindlimb muscular contraction evoked by ventral root (L7 and S1) stimulation were recorded in one group of anesthetized cats. Computer analyses were performed to determine if the resting discharge of VLM neurons correlated temporally with sympathetic nerve discharge and/or the cardiac cycle. The discharge rate of 21 of 27 neurons which had a discharge related to sympathetic nerve activity increased during muscular contraction. Neurons in some of the experiments were tested for axonal projections to the intermediolateral nucleus (T2 or T5) of the spinal cord with antidromic activation techniques. The discharge pattern of 78% of the VLM neurons which were activated antidromically was related to the cardiac cycle or sympathetic nerve discharge. Most (92%) reticulospinal VLM neurons with cardiovascular related discharge were excited by muscular contraction. In a second set of experiments, glutamate immunoreactivity was demonstrated in neurons within an area overlapping the location of VLM neurons which were excited by muscular contraction. These findings suggest that reticulospinal neurons in the ventrolateral medulla which have a discharge pattern related to cardiovascular activity contribute to the pressor reflex evoked by muscular contraction. These neurons may utilize glutamate as a neurotransmitter. PMID- 1596740 TI - Intracerebroventricular administration of neuropeptide Y affects parameters of dopamine, glutamate and GABA activities in the rat striatum. AB - The effects of intracerebroventricular (ICV) injection of neuropeptide Y (NPY) on parameters of dopamine (DA), glutamate (Glu) and gamma-aminobutyric acid (GABA) activities were investigated in the rat striatum. NPY (1.17-4.70 nmol) induced a dose-dependent increase in the striatal endogenous DA release monitored in freely moving animals by means of a voltammetric method. Maximal increase was observed about one hour after the peptide injection. This result is consistent with the hypothesis that NPY may influence striatal DA turnover in a facilitatory manner by activating DA release. DA, DOPAC, Glu and GABA endogenous contents as well as 3H-Glu and 3H-GABA synaptosomal high affinity uptakes were examined one hour after NPY ICV administration at the same dose range in chloral hydrate anesthetized animals. Depending on the NPY dose injected, opposite changes in Glu uptake were observed, suggesting that NPY has a bimodal influence on glutamatergic transmission. The Glu uptake rate increased markedly at 1.17 nmol NPY and decreased at 4.70 nmol, which may reflect an activation and an inhibition of the striatal Glu transmission, respectively. In parallel, the GABA uptake was found to decrease slightly at the higher doses of NPY tested, whereas no significant alteration of the striatal concentrations of either DA, DOPAC, Glu or GABA was observed. These results indicate that NPY may be involved in regulating the activity of nigral dopaminergic and cortical glutamatergic afferent pathways and that of intrinsic GABA neurons in the rat striatum. PMID- 1596741 TI - Transplantation of fetal cholinergic neurons into the hippocampus attenuates the cognitive and neurochemical deficits induced by AF64A. AB - The present experiments examined whether transplanted fetal cholinergic neurons would attenuate the behavioral and neurochemical deficits induced by the cholinotoxin AF64A (ethylcholine aziridinium ion). Bilateral injections of AF64A (3 nmol) into the lateral ventricles produced significant learning and memory impairments together with decreases in hippocampal high-affinity choline uptake (HAChU). AF64A-treated rats were impaired on both a standard radial arm maze (RAM) task and a working memory version in which a one-hour delay was imposed between the fourth and fifth arm choices. Transplantation of embryonic day E-17 septal/diagonal band tissue into the hippocampus (HPC) promoted recovery of performance on the standard version of the RAM task. However, this recovery was not observed when the animals were tested on the more difficult delay version of the task. Neurochemical analysis indicated that AF64A produced a significant (31%) decrease in hippocampal HAChU that was attenuated (14%) by transplantation of fetal cholinergic neurons. Histological analysis revealed that the transplants survived and innervated the HPC. There was no apparent relationship between fiber ingrowth into the HPC and behavioral recovery. These data indicate that transplant-induced behavioral recovery may be related to and limited by the cognitive demands of the testing situation. Generalized increases in cholinergic activity, transplant-mediated release of trophic factors, or a combination of both may underlie the behavioral recovery observed in the present studies. PMID- 1596742 TI - Cocaine elevates striatal dopamine efflux in spontaneously hypertensive and Wistar-Kyoto rats. AB - The effects of acute cocaine administration on central dopaminergic systems were examined in the striata of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats with the use of an in vivo microdialysis technique. Increased extracellular levels of dopamine were observed for 45 to 75 minutes following acute cocaine administration in both halothane-anesthetized and conscious SHR and WKY. However, no significant differences were noted between anesthetized and conscious SHR and WKY in either baseline levels or cocaine-induced changes in extracellular levels of dopamine and its metabolites. A positive, linear correlation between extracellular levels of dopamine and cocaine was demonstrated for the 60-min period following acute cocaine administration in both SHR and WKY. The slopes of the linear regression plots obtained from the data of each 15-min sample was slightly, but significantly, higher in conscious SHR than in conscious WKY. The present results suggest a transient and dose-related stimulation of striatal dopamine release following acute cocaine administration and a linear relationship between striatal extracellular levels of dopamine and cocaine in both SHR and WKY. PMID- 1596744 TI - Visual and somatosensory information to tongue motoneurons. AB - The experiments were designed to show whether visual inputs and somatosensory signals travelling along the common radial nerves converge onto the same hypoglossal neurons. The hypoglossal neurons (HN) type I (45.77%) and II (33.89%) responded to both visual and somatosensory stimuli. The HN type III (15.26%) responded only to the retinae and type IV (5.08%) only to the forelimb nerves stimulation. In the convergent neurons, types I and II, the influence of the somatosensory stimulation on the hypoglossal visual response was also analyzed. The conditioning stimulation of the radial nerve significantly increased (31%) the hypoglossal response to the less effective retina and significantly reduced (17%) the response to the more effective retina. The recordings of the electromyographic activity of the genioglossus (GM) and the superior longitudinal muscle (SLM), showed that the somatosensory afferents synergize the excitatory effect of the visual messages on the extrinsic tongue muscles (GM) and antagonize the inhibitory effect that visual messages induce on the intrinsic tongue muscles (SLM). The results suggest that visual messages induce tongue reflex responses functionally directed not only to prepare the oral cavity better for food reception, as previously demonstrated, but also to modulate the postural tone of the tongue together with somatosensory signals. PMID- 1596745 TI - Prenatal protein malnutrition alters behavioral state modulation of inhibition and facilitation in the dentate gyrus. AB - We have examined the effects of prenatal protein malnutrition on interneuronally mediated inhibition and facilitation in the dentate gyrus of the rat using the paired-pulse technique. Field potentials were recorded in the dentate gyrus in response to paired stimuli delivered to the perforant path. The paired-pulse index (PPI) was used as a measure of the net short-term facilitation or interneuronally mediated inhibition effective at the time of the paired-pulse test and was computed by dividing the amplitude of the second population spike (p2) by the amplitude of the first population spike (p1). PPIs were classified according to p1 in order to compare PPIs between behavioral states and dietary treatments since population spike amplitudes in the dentate gyrus vary in relation to behavioral state. Testing was performed during 4 behavioral states: slow-wave sleep (SWS), paradoxical sleep (REM), immobile waking (IW) and exploratory locomotion (AW) using interpulse intervals (IPI) from 20 to 400 ms. The magnitude and duration of interneuronally mediated inhibition was significantly increased in prenatal protein malnourished animals when compared with controls. Paired-pulse tests performed using an IPI of 20 ms under the high p1 (p1 greater than median) condition showed significantly smaller PPIs in prenatal protein malnourished rats regardless of behavioral state. For IPIs greater than 20 ms PPIs were consistently smaller in prenatal protein malnourished rats during SWS and IW. These data indicate that both the magnitude and duration of interneuronally mediated inhibition are increased in prenatally malnourished rats. No consistent diet-related differences were found during AW and REM using IPIs greater than 20 ms because interneuronally mediated inhibition was relatively suppressed during these behavioral states for both dietary groups. There was no consistent behavioral state modulation of paired-pulse facilitation (IPI = 40 to 80 ms) or late inhibition (IPI = 400 ms) in either diet group. In addition, a new relation between PPI and IPI was found under the low p1 (p1 greater than median) condition. During AW the PPIs observed using IPIs of 40 and 50 ms were smaller than those observed using IPIs of 30 and 60 ms. This depression interrupts what is generally considered the "facilitatory" phase of paired-pulse response and may indicate an interaction between perforant path stimulation and hippocampal theta rhythm which is masked when p1 amplitude is high.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1596743 TI - Kynurenine and probenecid inhibit pentylenetetrazol- and NMDLA-induced seizures and increase kynurenic acid concentrations in the brain. AB - Kynurenine is a direct precursor of kynurenic acid, the only known endogenous antagonist of excitatory amino acid receptors in the brain. Kynurenine administered intraperitoneally (150, 450, 900 mg/kg) 2 h before pentylenetetrazol injection dose-dependently increased the time to seizures, the time to death and the survivorship of mice. Kynurenine dose-dependently increased the time to seizures and the time to death in mice with NMDLA-induced seizures. Kynurenine, 900 mg/kg, was equally efficacious to diazepam, 2 mg/kg. Probenecid dose dependently increased the time to seizures, the time to death and the survivorship of mice with pentylenetetrazol-induced seizures. Probenecid had no significant effects on NMDLA-induced seizures, although the time to death was prolonged in the NMDLA 500 mg/kg group. Probenecid potentiated the effects of kynurenine in these tests. Both probenecid and kynurenine significantly increased kynurenine and kynurenic acid concentrations in mouse cerebral cortex and striatum. These findings suggest that kynurenine (metabolized to kynurenic acid) has anticonvulsant effects, and probenecid potentiates these effects in mice. PMID- 1596747 TI - The neurobiological effects of colchicine: modulation by nerve growth factor. AB - To study the effects of exogenously applied nerve growth factor (NGF) on colchicine-induced neurodegeneration in the dentate gyrus of the rat hippocampal formation, colchicine (COLCH) or artificial cerebrospinal fluid (ACSF) was infused into the dorsal hippocampus (HPC) followed by unilateral infusion of either purified beta-NGF (in ACSF) or cytochrome C. One week later, animals were tested in activity chambers when NGF treatment was found to reduce the COLCH induced hyperactivity. Animals were sacrificed 3 or 12 weeks postlesion for neurochemical or morphological analysis. Carbachol-stimulated phosphatidyl inositol (PI) turnover performed in hippocampal slices was not affected by any treatment at 3 weeks. However, 12 weeks after the lesion, CARB stimulation of PI hydrolysis was increased in the COLCH/ACSF group. NGF treatment significantly reduced the hyperstimulation in COLCH-treated rats. Morphological analysis showed that COLCH treatment increased AChE staining in the hippocampus, whereas NGF treatment had no effect on AChE staining. There was no difference in the number of septal ChAT immunoreactive cell bodies of controls or colchicine-treated rats at either time point examined. However, NGF treatment resulted in a significant increase in the number of ChAT immunoreactive cell bodies 3 weeks postlesion. Results from this study indicate that NGF can modify colchicine-induced compensatory changes in hippocampal signal transduction and has transitory influences on cholinergic cells in the medial septum. PMID- 1596746 TI - Central and systemic oxytocin release: a study of the paraventricular nucleus by in vivo microdialysis. AB - The mechanisms controlling central and systemic oxytocin (OT) release were examined using in vivo microdialysis of the paraventricular (PVN) region. Dialysate and plasma samples were collected from conscious male rats and stimuli were administered via the dialysate fluid. Characterization studies showed that microdialysis was a viable technique for the study of peptide secretion in the conscious animal. OT was consistently detected in the PVN dialysate and a partially purified extract crossreacted in parallel fashion with the synthetic peptide. In vitro studies showed that peptide recovery was positively correlated with the pore size of the dialysis membrane and that there was an inverse relationship between flow rate and recovery. Hypertonic saline administered centrally caused an increase in dialysate and plasma oxytocin while the intravenous injection affected only plasma oxytocin. The excitatory amino acid, glutamate (0.05-0.5 M), caused an increase in plasma, but not dialysate oxytocin, while depolarization with potassium chloride (0.05-0.15 M) had no significant effects. Histological examination showed that the dialysis probe was located in the rostral, lateral PVN. Our results show that in vivo microdialysis provides a method for the delivery of drugs into specific brain regions as well as a useful technique for the evaluation of in vivo neuropeptide release. PMID- 1596748 TI - Central effects of neuropeptide K on water and food intake in the rat. AB - The present study investigated the effect on water and food intake in the rat of the intracerebroventricular (ICV) injection of neuropeptide K (NPK), the N terminally extended form of neurokinin A. NPK inhibited water deprivation-induced water intake even at 31.2 ng/rat. At higher doses, it inhibited also water intake induced by ICV angiotensin II or by subcutaneous hypertonic NaCl, and food associated drinking, the threshold dose being 125 ng/rat. In response to 125 ng/rat, food intake following 16 h food deprivation was not reduced. NPK inhibited food intake only at 500 ng/rat, a dose that evoked excessive grooming in treated animals. Thus NPK is a potent inhibitor of water deprivation-induced drinking and at higher doses it exerts a general antidipsogenic effect towards several dipsogenic determinants, without affecting food intake. On the other hand, it inhibits food intake only at high doses, 500 ng/rat or more, but this inhibition might be just related to the intense grooming evoked. The effects of NPK on ingestive behavior are markedly different from those of neurokinin A, which selectively inhibits osmotic drinking and food-associated drinking. These differences suggest that NPK itself may exert its effects on the central nervous system, not necessarily through the conversion to neurokinin A. PMID- 1596749 TI - Effect of (+)MK-801 and ketamine on rapid tolerance to ethanol. AB - The motor impairment (tilt-plane test) responses to ethanol were significantly reduced on days 2, 3, 4, or 5 in rats receiving ethanol (2.3 and 1.7 g/kg) 24 and 22 h earlier, compared to the control group pretreated with saline. Administration of (+)MK-801, prior to behavioral testing with ethanol on day 1, inhibited the development of tolerance on all these days. Tolerance and the inhibitory effect of (+)MK-801 could no longer be seen if the second injection of ethanol was given on day 7, 8 or 11. Administration of (+)MK-801 on day 1 but after behavioral testing with ethanol did not block the development of rapid tolerance to ethanol on day 2. Administration of another commonly employed NMDA antagonist, i.e., ketamine, prior to ethanol on day 1, also blocked the development of rapid tolerance to ethanol. The findings suggest that NMDA antagonists block rapid tolerance by preventing some adaptation that occurs during intoxicated practice. PMID- 1596750 TI - Apomorphine- and oxytocin-induced penile erection and yawning in male rats: effect of pertussis toxin. AB - The effect of the intracerebroventricular (ICV) administration of pertussis toxin on penile erection and yawning induced by apomorphine and oxytocin was studied in male rats. Pertussis toxin (2 micrograms ICV) prevented the above behavioral responses to apomorphine (80 micrograms/kg SC) and oxytocin (30 ng ICV) on day 3 and 4, but not on day 0 and 1 after treatment. Oxytocin and apomorphine responses were restored on day 6. Similar results were obtained by microinjecting pertussis toxin (0.5 microgram) in the paraventricular nucleus of the hypothalamus, the most sensitive brain area for the induction of penile erection and yawning by oxytocin and apomorphine. The results suggest that G proteins are involved in the expression of above responses to apomorphine and oxytocin. PMID- 1596751 TI - Sex steroids possess distinct stimulus properties in female and male mice. AB - Very few studies have investigated the aversive properties of sex steroids in animals. We studied these properties by testing oestradiol-3-benzoate, testosterone-propionate and progesterone in a conditioned taste aversion set-up, in intact female and male mice. Oestradiol-3-benzoate induced a taste aversion in both female and male mice; however, testosterone-propionate and progesterone had an effect only in females. These results show that sex steroids have intrinsic aversive properties. The different effects of the steroids in males and females cannot simply be explained by nausea induction or novelty. PMID- 1596752 TI - Generation of end-inhibition in striate neurons in rabbits. AB - Eighty-six rabbit striate neurons were tested with lateral microinjection of lidocaine, GABA or bicuculline. Seven of the neurons expressed different levels of end-inhibition. We examined these end-stopping units by injection of lidocaine or bicuculline in adjacent areas in order to determine if a lateral cortical mechanism is underlying end-inhibition in rabbits as it has been proposed in cats. Microinjection of lidocaine resulted in an attenuation of the end inhibition strength. Application of bicuculline had the opposite effect; the end inhibition was reinforced. We suggest that as observed in cats, in rabbits end inhibition is mediated through horizontal cortical connections which implies a postsynaptic inhibitory input to the end-stopping cell. PMID- 1596753 TI - Reduction of seizure frequency by clonazepam during cobalt experimental epilepsy. AB - Adult female Sprague-Dawley rats rendered epileptic by bilateral cerebral implantation of cobalt wire were simultaneously prepared with permanent cortical and temporalis muscle electrodes for continuous recording of electroencephalographic (EEG) and electromyographic (EMG) activities. Clonazepam (4, 10 or 40 mg/kg) dissolved in gum acacia was administered once daily intraperitoneally for 5 days beginning 9 days after cobalt implantation. The 40 mg/kg dose completely suppressed generalized seizure activity. Although no tolerance to this effect developed by the fifth day of treatment, generalized seizure activity two days after the last injection was significantly greater in epileptic rats than in control animals. These results suggest that the cobalt model of epilepsy may be useful in the study of mechanisms underlying both anticonvulsant effectiveness and rebound excitability after anticonvulsant drug withdrawal. PMID- 1596754 TI - Taste neurons in the cortex of the alert cynomolgus monkey. AB - The activity of single neurons in the gustatory cortex of alert cynomolgus monkeys was analyzed. Taste-evoked activity in response to the four prototypical taste stimuli was recorded from a cortical gustatory area comprising the frontal operculum and adjoining anterior insula. Spontaneous activity for 364 gustatory neurons was 3.9 +/- 4.9 (mean +/- SD) spikes/s. Mean net (gross minus spontaneous) discharge rates for all gustatory neurons were: 1.0 M glucose = 4.9 +/- 11.6, 0.3 M NaCl = 3.2 +/- 7.1, M quinine HCl = 2.6 +/- 5.8, and 0.01 M HCl = 1.7 +/- 4.6. The results from intensity-response functions imply that the perception of each basic taste quality in the nonhuman primate is based on the activity of the appropriate neural subgroup rather than on the mean activity of all taste cells. Therefore a more meaningful index of the effectiveness of a stimulus may be the discharge rate it evokes from the subset of gustatory neurons for which it is the best stimulus. Glucose was the best stimulus for 142 cells (including ties), from which it elicited a mean net response of 10.3 spikes/s; NaCl was best for 107 neurons which gave a mean 8.7 spikes/s; quinine HCl evoked 6.2 spikes/s from the 74 cells that responded best to it; HCl elicited 5.9 spikes/s from the 49 neurons for which it served as best stimulus. The response characteristics of cortical taste cells indicate heterogeneous features, and significantly different patterns from those reported in other nonchemical sensory systems. PMID- 1596755 TI - Intraventricular administration of D-Ala2-Met5-enkephalinamide induces rapid recovery of responding for electrical brain stimulation from the ventral tegmental area following uncontrollable footshock. AB - The effects of uncontrollable footshock were assessed in CD-1 mice responding for electrical brain stimulation (ICSS) from the dorsal aspects of the ventral tegmental area (VTA). Uncontrollable footshock provoked a marked reduction of responding for ICSS immediately, 24 h and 168 h following initial stressor exposure. Intraventricular administration of the neuropeptide, D-Ala2-Met5 enkephalinamide (DALA) (1 microgram/microliter delivered in a 1-microliter volume) following induction of reward alterations from the dorsal VTA provoked a rapid recovery of responding for ICSS in the immediate poststressor interval. This ameliorative effect of the neuropeptide deteriorated 24 h after initial exposure to uncontrollable footshock and was absent 1 week later. These data are discussed with respect to stressor-induced anhedonia in the mesocorticolimbic system. PMID- 1596756 TI - Architecture of the suprachiasmatic nuclei in BALB/c and C57BL/6 inbred mouse strains. AB - Quantitative values representing the length, girth, volume, shape, and cell counts of the suprachiasmatic nuclei (SCN) were measured in BALB/cByJ and C57BL/6J inbred mouse strains, which exhibit a large interstrain difference in the free-running period of their circadian locomotor rhythms. There were no differences in the gross architectural features of the SCN in these two strains. PMID- 1596757 TI - Naloxone blocks opioid peptide release in N. accumbens and amygdala elicited by morphine injected into periaqueductal gray. AB - It has been proposed that a serial, unidirectional circuit from the PAG to the N. accumbens and the amygdala are involved in antinociception and that enkephalins (ENK) and beta-endorphin (beta-EP) act as neurotransmitters in this circuitry. In the present study, we measured the release of ENK and beta-EP by simultaneous push-pull perfusion of the N. accumbens and amygdala after microinjection of morphine into the PAG. Morphine administration elicited an increase in immunoreactive ENK and beta-EP in both the N. accumbens and the amygdala, which was antagonized in each nucleus by perfusion with naloxone. These data suggest that the three nuclei were not serially connected and that they may take part in one and the same antinociceptive system with an "all or none" character. PMID- 1596758 TI - CAR ad hoc committee for mammography accreditation. PMID- 1596759 TI - Crohn's disease of the proximal small intestine: radiologic findings in 55 patients. AB - Radiographs of the upper gastrointestinal tract and the small bowel of 55 patients were reviewed to identify changes associated with proximal enteric Crohn's disease. Five patients had gastroduodenitis, 18 duodenitis, 14 jejunitis and 18 jejunoileitis. Nineteen had previously undergone ileocecal resection. The terminal ileum was spared in 11 of the 36 patients who had not undergone ileocecal resection; of these, 9 had jejunoileitis, 1 jejunitis and 1 jejunitis secondary to colitis with colojejunal fistulas. In just over 80% of the patients with jejunal disease and all the patients with primary jejunal disease in whom the terminal ileum was spared, the condition developed before the patients reached 30 years of age. Duodenal disease was not associated with any particular age group, and duodenitis was invariably a "skip" lesion in patients with disease of the terminal ileum. The diagnosis of proximal enteric Crohn's disease depended on the presence of one or more characteristic lesions in the jejunum or terminal ileitis associated with a duodenal or jejunal abnormality. Ulceration occurred in 88% of the patients with a diseased terminal ileum but was less common in patients with a diseased duodenum (occurring in 43%), jejunum (in 53%) or proximal ileum (in 57%). Fistulas in the terminal ileum complicate ulceration in 10% to 26% of patients, and sinuses complicate ulceration slightly more often, but proximal enteric fistulas or sinuses occurred in only four (7%) of the patients described here.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596760 TI - Prenatal diagnosis of urinary tract malformations. AB - Oligohydramnios, abnormal kidneys or an abnormal bladder, separately or in combination, are the usual ultrasonographic signs that call attention to an anomaly of the fetal urinary tract. After briefly outlining the normal anatomic features, the author elaborates on these three major signs and discusses bilateral renal agenesis, paradoxic polyhydramnios, obstructive and nonobstructive hydronephrosis, renal cystic disease and urethral obstruction. Radiologists who perform obstetric ultrasonography must be familiar with the general pathophysiologic principles that pertain to the fetal urinary tract, as well as their ultrasonographic manifestations. PMID- 1596761 TI - Resident training in breast imaging in Canada: current status. AB - The authors evaluated the current status of resident training in breast imaging in Canada to provide baseline data for guidelines on the amount and the nature of training necessary. Information was obtained, by means of a questionnaire or a telephone interview, from the directors of all 16 radiology residency programs and the 58 radiology residents in their final year at the time of the study. All programs offer training in breast imaging; the training is mandatory in 11 (69%) and elective in 5 (31%). Of the 58 residents, 52 had had some training in breast imaging at the time of the study. Of these, 24 (46%) had spent a period averaging 3.9 weeks exclusively on breast imaging. Forty-one percent of residents felt that the duration of their breast imaging training was too short, and 35% felt that they could not practise mammography independently after their rotation. The authors found that training in breast imaging across the country is highly variable. Although this training is being upgraded in many programs, deficiencies remain. Guidelines are needed to ensure a minimum standard for training in breast imaging. PMID- 1596762 TI - Medical audit of mammography: a simplified alternative. AB - Assessing radiologists' mammographic interpretation and performing a complete audit of a mammographic practice are notoriously difficult and time consuming. The authors propose a simplified method for accomplishing a satisfactory medical audit. A search of the 1987 pathological reports of St. Michael's Hospital in Toronto yielded 153 patients who underwent excisional biopsy of the breast and for whom preoperatively obtained mammograms were available. The medical records of the patients were reviewed to obtain demographic data, as well as information as to whether the excised lesions had been palpable and the stage of the tumour. The mammograms of the patients were categorized retrospectively by four independent observers. The findings were correlated with the results of the pathological examinations and analysed with receiver-operating characteristic (ROC) curves. Forty-five nonpalpable and 121 palpable lesions were identified, of which 70 were malignant and 96 benign. The positive predictive value of mammography for the nonpalpable lesions was 20%. Three of the 9 nonpalpable cancers and 35 of the 56 palpable ones had metastasized to the axillary lymph nodes. The area under the ROC curves for the four radiologists ranged from 0.84 to 0.89. This audit method in inexpensive and easily applied. PMID- 1596763 TI - Heterotopic ossification in children after iliopsoas release. AB - Heterotopic calcification or ossification of the soft tissues adjacent to the lesser trochanter was observed in the radiographs of 4 patients during a retrospective review of the records of 68 patients with Perthes' disease. This abnormality has since been seen in one other patient with Perthes' disease and in five with spastic quadriplegia. All 10 patients are known to have undergone iliopsoas release as part of adductor tenotomy. The authors believe that the heterotopic ossification is related to the surgery. PMID- 1596764 TI - Tuberculosis of the odontoid bone: a rare but treatable cause of quadriplegia. AB - Radiologic investigation plays an important role in the diagnosis and management of tuberculosis of the odontoid bone. Immediate confirmation of the condition by examination of tissue and surgery may save lives and reduce the morbidity rate substantially. When the clinical history is appropriate, a diagnosis of tuberculosis is strongly suggested by plain films of the cervical spine showing precervical swelling of the soft tissues, narrowing of the disk spaces and focal erosion of the bones and by computed tomography scans demonstrating details of the soft-tissue abnormality, focal bony erosion and sclerosis. PMID- 1596765 TI - Symptomatic calcific tendinitis at unusual sites. AB - Three cases of symptomatic calcific tendinitis at unusual sites (in the vastus lateralis tendon, the rectus femoris tendon and the flexor carpi ulnaris tendon) are presented. In two, the plain radiographs were nondiagnostic, and the diagnosis was made on the basis of the findings in computed tomography (CT) scans. The value of CT in examining atypical patients is demonstrated. PMID- 1596766 TI - Infradiaphragmatic pulmonary sequestration. AB - The authors describe two patients with intra-abdominal pulmonary sequestration presenting as a suprarenal mass in antenatal ultrasonography (US) images. In both cases the suprarenal mass was echogenic, and in one the mass also contained small hypoechoic areas. US and computed tomography performed after birth demonstrated feeding vessels in the suprarenal mass of one neonate; colour-flow Doppler US demonstrated the smaller feeding vessels to greater advantage. PMID- 1596767 TI - Antenatal and postnatal findings in intra-abdominal pulmonary sequestration. AB - A hyperechoic mass in the right upper quadrant of the abdomen was demonstrated in a fetus by antenatal ultrasonography (US) at 20 and 33 weeks' gestation. Postnatal US, myelography and computed tomography were performed preoperatively; the findings were judged consistent with neuroblastoma. Surgical excision and pathological examination revealed bronchopulmonary sequestration. PMID- 1596768 TI - Gastroduodenal involvement in chronic granulomatous disease of childhood. AB - Obstruction of the gastric outlet as a complication of chronic granulomatous disease (CGD) is uncommon. The usual findings in a barium examination of the upper gastrointestinal tract are irregular antral mucosal folds and antral narrowing. There is typically a sharp demarcation of the affected area from the normal proximal stomach. The authors report a case of CGD of childhood in which there was diffuse gastric involvement with extension into the duodenal cap. The patient recovered with conservative therapy after a diagnostic exploratory laparotomy. PMID- 1596769 TI - Juvenile hypertrophy presenting as a discrete breast mass. AB - Juvenile hypertrophy of the breast usually presents as diffuse enlargement of the breasts in young women. The authors describe a patient in whom hypertrophy presented as a discrete mass, which was both visible in mammograms and palpable. PMID- 1596770 TI - Growth of a leiomyosarcoma of the inferior vena cava. AB - Until recently, leiomyosarcoma of the inferior vena cava was rarely diagnosed preoperatively. The authors describe a patient who was treated for 12 months on the basis of a presumptive diagnosis of thrombosis of the inferior vena cava. Abdominal ultrasonography and computed tomography demonstrated interval growth, and venous biopsy revealed a malignant spindle-cell neoplasm. Surgical excision confirmed the presence of a leiomyosarcoma, which had grown slowly for at least several months before entering a phase of accelerated growth. PMID- 1596771 TI - Leiomyosarcoma of the femoral vein. AB - Soft-tissue masses uncommonly completely occlude or engulf a major vessel. Complete occlusion of a major vein suggests that the mass originates in the wall of the vein. Such tumours are rare, the most frequently encountered type being leiomyosarcoma. The authors present a case of leiomyosarcoma of the femoral vein. PMID- 1596772 TI - Colour-flow Doppler imaging of a carotid-cavernous fistula. AB - The authors describe a case of carotid-cavernous fistula evaluated with both conventional carotid angiography and colour-flow Doppler ultrasonography. The findings in the colour-flow Doppler images correlated well with those from angiography; in addition, Doppler imaging supplied extra information about the direction and the velocity of flow. After embolization, colour-flow Doppler imaging demonstrated a marked decrease in the flow. The authors conclude that colour-flow Doppler imaging may be useful for noninvasively detecting and evaluating a carotid-cavernous fistula, as well as for monitoring the patient's progress after therapy. PMID- 1596773 TI - Residents' corner. Answer to case of the month #13. Adenocarcinoma of a urachal cyst. PMID- 1596774 TI - Acidic phosphoproteins from bone matrix: a structural rationalization of their role in biomineralization. AB - Osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 are three acidic phosphoproteins that are isolated from the mineralized phase of bone matrix, are synthesized by osteoblastic cells, and are generally restricted in their distribution to calcified tissues. Although each is a distinct gene product, these proteins share aspartic/glutamic acid contents of 30-36% and each contains multiple phosphoryl and sialyl groups. These properties, plus a strict relationship of acidic macromolecules with cell-controlled mineralization throughout nature, suggest functions in calcium binding and nucleation of calcium hydroxyapatite crystal formation. However, direct proof for such roles is still largely indirect in nature. The purpose of this review is to present two speculative hypotheses regarding acidic phosphoprotein function. The goal was to use new sequence information along with database comparisons to develop a structural rationalization of how these proteins may function in calcium handling by bone. For example, our analysis has identified a conserved polyacidic stretch in all three phosphoproteins which we propose mediates metal binding. Also, conserved motifs were identified that are analogous with those for casein kinase II phosphorylation sites and whose number correlates well with that of phosphoryl groups/protein. A two-state conformational model of calcium binding by bone matrix acidic phosphoproteins is described which incorporates these findings. PMID- 1596775 TI - Bone density, mineral content, and cortical index in patients with thalassemia major and the correlation to their bone fractures, blood transfusions, and treatment with desferrioxamine. AB - In an attempt to explain the increased frequency of pathological fractures found in thalassemia major patients, we examined noninvasively several properties of bones in 17 patients. We found a significant decrease in the bone mineral content (BMC) and the bone density (BD) of both trabecular (34% and 4% diminution, respectively) and cortical bone (24% and 3% diminution, respectively), as compared with normal controls. We also found that metacarpal cortical indices (CI) were significantly lower in thalassemic patients as compared with normal controls (36% diminution). As expected, upper limb fractures were more frequent in those patients with greater bone diminution. Furthermore, the degree of bone diminution was greater in patients receiving fewer blood transfusions and shorter courses of desferrioxamine. Bone densitometry should probably be included in the comprehensive evaluation of thalassemia patients in order to help guide overall treatment. PMID- 1596776 TI - Calcitonin treatment in lumbar spinal stenosis: a randomized, placebo-controlled, double-blind, cross-over study with one-year follow-up. AB - A randomized, placebo-controlled, double-blind, crossover study in 40 lumbar spinal stenosis patients with a 1-year follow-up showed that calcitonin had beneficial effects on the patients' symptoms without producing any notable side effects. Calcitonin had a clear analgesic effect. The mean of walking distance increased, but the crossover trend was not as good as the analgesic effect. Side effects such as erythema and nausea were usually mild and transient. Calcitonin therapy can be used as a conservative treatment in selected cases of lumbar spinal stenosis. When rest pain was mild or the walking distance was under 200 300 m because of neurogenic claudication, the effect of calcitonin seemed to be poor. PMID- 1596777 TI - Bone mass and bone cellular variations after five months of physical training in rhesus monkeys: histomorphometric study. AB - Five Rhesus Monkeys (Macaca mulatta), a suitable nonhuman model, performed 5 months of rope-climbing exercise. Duration of the training sessions was progressively increased to reach 1 hour/day after 1 month of training and was maintained until the end of the experiment. Bone mass parameters, bone resorption, and bone formation activity were measured by histomorphometric analysis on iliac crest bone biopsies before and after the experiment. Mineral apposition rate was measured in cortices and trabecular bone after double calcein labeling. Five months of rope-climbing exercise had determined a significant decrease of bone volume with a slight decrease of the number and thickness of trabeculae. This might induce an alteration of biomechanical properties of bone. These architectural modifications were associated with a nonsignificant decrease of bone resorption activity. But the main effect of training was an important decrease of bone formation activity without change of the mineral apposition rate. Endurance exercise at low intensity has determined a decreased bone turnover with osteoblastic depression. This animal experiment points out that exercise modalities might be important in the bone response to training and should be carefully defined for preventive use in humans. PMID- 1596778 TI - Effect of sodium fluoride on bone density in chickens. AB - In addition to increasing bone volume, fluoride has been demonstrated to increase ash weight and mineral density. To determine whether newly formed or older bone is most affected by fluoride treatment, bone from chickens receiving fluoridated water was fractionated into lower density (recently formed) and higher density (more mature) specific gravity fractions. Fluoride was administered to the chickens for different lengths of time (4 or 13 weeks) or at varying doses for a 4-week period (0, 4.2, 16.8 mmol/liter drinking water). Fluoride treatment caused a shift in the mineral density profile, showing an increased proportion of mineral distribution in the more mature, higher density fractions. To determine whether this density gradient shift was due to increased maturation rate of bone or decreased resorption and mineralization rates, [3H]proline and 45Ca were injected 5 days and 24 hours prior to sacrifice, respectively. The distributions of both 3H or 45Ca, as percentages of total counts incorporated, were shifted by fluoride treatment into more mature, higher density fractions. Expressing the number of counts as a percent of the bone in each fraction (total hydroxyproline or Ca) revealed an increased incorporation of both 3H and 45Ca into the higher specific gravity fractions 2.0-2.2. These results suggest that fluoride treatment increases bone maturation and the rate of secondary mineralization in the cortical bone. Such changes in the quality of more mature, well-mineralized bone, in humans as well as animals, may have a significant influence on brittleness and strength. PMID- 1596779 TI - The role of magnesium on the structure of biological apatites. AB - X-ray diffraction, infrared absorption spectroscopy, and chemical investigation have been carried out on deproteinated samples of turkey leg tendon at different degrees of calcification. The inorganic phase consists of poorly crystalline B carbonated apatite. On increasing calcification, the apatite crystal size, as well as its thermal stability, increase while the relative magnesium content is reduced. On the other hand, synchrotron X-ray diffraction data clearly indicate that apatite lattice parameters do not change as the crystals get larger. At the last stage of calcification the crystal size, chemical composition, and thermal conversion of the apatite crystallites approximate those of bone samples, which have been examined for comparison. The results provide a quantitative relationship between relative magnesium content and extent of apatite conversion into B-tricalcium phosphate by heat treatment. Furthermore, they suggest that the smaller crystallites laid down inside the gap region of the collagen fibrils are richer in magnesium than the longer ones that fill the space between collagen fibrils. PMID- 1596780 TI - Coordinate inhibition of alkaline phosphatase and type X collagen syntheses by 1,25-dihydroxyvitamin D3 in primary cultured hypertrophic chondrocytes. AB - The effects of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) (2.3 x 10(-12) - 1.4 x 10( 6) [M]) on alkaline phosphatase, collagen, and cell proliferation were examined in primary cultured hypertrophic chondrocytes prepared from the distal epiphyseal growth plate of the tibias of 12-day chick embryos. 1,25(OH)2D3 showed time- and dose-dependent inhibitory effects on the alkaline phosphatase and collagen levels. The inhibition of alkaline phosphatase activity became detectable at 2 x 10(-11) [M] and reached 10% of control at 10(-7) [M]. The concentration of 1,25(OH)2D3 giving a 50% inhibition of the enzyme level was approximately 3 x 10( 10) [M]. Of the two extracellular collagen pools, a cell-associated matrix pool showed a more dramatic decrease (to 10% of control) than a culture medium pool (to 50% of control) at increased 1,25(OH)2D3 concentrations. The degree of inhibition was different for each type of chondrocyte-specific collagen (types II, IX, X, and XI). Types II and IX were inhibited in a parallel manner to only 60-80% of control. On the other hand, types X and XI were more greatly reduced up to 10% of control, and their dose-dependent inhibitory curves were similar to that of alkaline phosphatase. On cell proliferation, 1,25(OH)2D3 had a biphasic effect: stimulation at 10(-10)-10(-8) [M] and inhibition at higher levels. The results revealed the significant involvement of 1,25(OH)2D3 in the metabolism of two probable calcification-related products, alkaline phosphatase and type X collagen. PMID- 1596782 TI - The role of osteonectin in human tooth development: an immunohistological study. AB - We investigated immunohistologically 160 teeth and dental germs in various stages of tooth development taken from human individuals (13th week of pregnancy to the 24th year of life) to study the osteonectin expression in dental hard tissue. In the course of dentinogenesis, the predentin, the odontoblasts, and their cell processes show a positive osteonectin staining reaction. During cementogenesis, osteonectin is synthesized by cement-producing fibroblasts, cementoblasts, and cementocytes. The expression of osteonectin during dentinogenesis and cementogenesis is closely related to the development of the respective calcified tissue. All cells of the inner and outer enamel epithelium, the cells of the stratum reticulare and stratum intermedium, the ameloblasts, and the enamel substance are osteonectin negative, just as dentin and cement are. The results of this study indicate one important physiological role of osteonectin as a protein associated with the formation of collagen containing mineralizing tissues like human bone, as well as human dentin and cement. PMID- 1596781 TI - Lead intoxication alters basal and parathyroid hormone-regulated cellular calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells. AB - The skeleton is the major reservoir of lead and calcium in humans, and plays an important role in systemic calcium regulation. Lead perturbs normal calcium transport and second messenger function, directly or indirectly, in virtually all cells studies so far. Therefore, we and others have postulated that an early and discrete toxic effect of lead is perturbation of one or more loci within the calcium messenger system. To understand further the role of lead on calcium homeostasis in bone, we undertook this study to characterize calcium homeostasis and the effect of lead on calcium homeostasis in rat osteosarcoma (ROS 17/2.8) cells, which exhibit the osteoblast phenotype. ROS cells were incubated in medium containing 45Ca for 20 hours. Monitoring the efflux of 45Ca from the cultures for 210 minutes allowed for the determination of kinetic parameters defining steady state calcium homeostasis. Three distinct intracellular kinetic calcium pools characterized 45Ca homeostasis. Treatment with either 400 ng parathyroid hormone (PTH)/ml culture medium for 1 hour or 25 microM lead for 20 hours increased total cell calcium. Treatment with PTH caused a larger increase of cell calcium in lead intoxicated cells than either lead intoxication or PTH treatment alone. This increase suggests that lead may perturb normal calcium-mediated PTH responsiveness of the osteoblast. These experiments further establish a kinetic model for the study of calcium homeostasis in osteoblastic bone cells. The studies also advance the hypothesis that lead-induced perturbations of calcium mediated processes represent an early effect of lead toxicity at the cellular level. PMID- 1596784 TI - [Multiple organ failure after severe burns]. AB - 36 cases with multiple organ failure (MOF) in a group of 178 severe burn injury patients during 1969-1989 were observed in our department. The rate of occurrence of MOF in this group was 20.2% (36/178). 25 cases out of these 36 patients died, and the mortality rate was 69.5% (25/36). In 10 cases 2 organs were involved, and two patients died; 3 organs were involved in 13 cases and nine of them died; more than 4 organs were affected in 13 cases and all of them died. The relationship between MOF and shock, inhalation injury as well as septicemia was discussed. Although there were many factors which could induce postburn multiple organ failure (PBMOF), the severity of the injury was the most fundamental inducing factor. The severer the burn injury, the higher the morbidity and mortality of PBMOF. Both shock and inhalation injury were important inducing factors in early PBMOF. Wound sepsis and septicemia were major inducing factors in delayed PBMOF. Majority of the delayed PBMOF took place during septicemia. In consideration of the high mortality of PBMOF and lack of effective treatment at present, it is extremely important to prevent severe burn injury patients from developing PBMOF. The measures to prevent PBMOF included: to correct shock adequately as soon as possible, to select the optimal time and appropriate extent of escharotomy and skin grafting, to try our best to ensure complete or near complete take of skin grafts, and to strengthen systemic metabolic support. PMID- 1596783 TI - Time-dependent changes of collagen cross-links and their precursors in the culture of osteogenic cells. AB - The early stage of cross-link formation in bone collagen was studied in a cell culture system. An osteogenic cell line that produces and accumulates a remarkably high amount of collagen, and that eventually forms bone-like structures, was used in this study for its time-dependent development of reducible cross-links. It was found that precursors of the cross-link, dehydro dihydroxynorleucine and dehydro-hydroxynorleucine became detectable as soon as the cells attained a confluent state. They showed maximal amounts at days 3-5 after confluence, but substantially disappeared at day 10 after confluence. In contrast, two characteristic cross-links of bone collagen, dehydro dihydroxylysinorleucine (dehydro-DHLNL) and dehydro-hydroxylysinorleucine (dehydro-HLNL), which were present in trace amounts at the stage of cell confluence, gradually increased in amount and reached a plateau at day 10, just when their precursors disappeared. Thus, it was found that there was a time lag of about a week between the maximal formations of precursors and cross-links of bone collagen in this system. The significance of this time lag was interpreted in terms of the minimum essential accumulation of collagen for the precursor product transition. The ratio of dehydro-DHLNL to dehydro-HLNL was as low as 0.7 at day 3 after confluency, increased to 4.2 at day 20, the period just before mineralization began, and decreased thereafter, suggesting a qualitative change in bone collagen associated with mineralization. PMID- 1596785 TI - [Experimental study on early multiple organ failure after severe burns]. AB - Forty-three male mongrel dogs (12.5 +/- 2.5 kg) were divided into normal control (n = 7), immediate infusion (n = 8), non-infusion (n = 13) and delayed infusion (n = 15) groups. A 50% TBSA third degree surface burn was produced by igniting 3% napalm for 30 seconds on the shaved back. Cardiac, pulmonary, hepatic, renal and gastrointestinal functions were monitored following the thermal injury. The findings of these studies showed that mean arterial pressure, cardiac index, left ventricular work, right ventricular work, ADP/O ratio and ATP were all significantly decreased (P less than 0.05). However pulmonary artery wedge pressure, pulmonary vascular resistance, systemic vascular resistance, P(A-a)O2, Beef, Cr, UN, ALT, LDH, TB, DB, and MDA were markedly increased (P less than 0.05). Severe shock occurred soon after burns. Thirteen dogs died within 12 hours in the non-infusion group. All the dogs were resuscitated when immediate infusion of lactic acid Ringers solution was given according to Parkland formula, and all of them tide over shock stage smoothly without obvious changes in visceral functions. However, dogs were not resuscitated when infusion was delayed 6 hours postburn. The changes in visceral were even more severe in this group than those in non-infusion group. These results demonstrated that delayed resuscitation was an important factor of MOF in the early postburn stage. The marked increase in MDA in the myocardiac, lung, liver, renal and gastrointestinal tissues indicated that lipoperoxidation by free oxygen radicals was closely related with visceral damages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596786 TI - [An animal model of posttraumatic multiple system organ failure (MSOF)]. AB - Hemorrhagic shock, sepsis, excessive systemic inflammatory reactions, and failure of intestinal mucosal barrier function are known to be major predisposing factors in the development of MSOF in patients after severe trauma or burns. We investigated the possibility of complicating clinically simulating MSOF in animals. Our results showed that, with compounded traumatic factors, including damages to the bowel, and proper circulatory and respiratory support, an animal model which simulated the pathophysiology and histopathology of MSOF could be reproduced to offer opportunity for the study of mechanisms and therapy. Markers of MSOF were also described for reference. PMID- 1596787 TI - [Immunochemical study of Cu-Zn-superoxide dismutase (Cu-Zn-SOD) in multiple organ failure of rats]. AB - 70 Wistar rats were divided into normal group and experimental group (intra peritoneal injection of zymosan (75mg per 100g wt). All rats were sacrificed at 1, 2 and 4-5 days. The histological changes in the lung, liver, kidney and brain agreed with the alterations recognized in multiple organ failure. On immuno histochemical examination, we found that the content of Cu-Zn-SOD in bronchiolar columnar cells, liver cells, renal tubular epithelial cells and neuron cells of brain was decreased as compared with normal control group (P less than 0.05 or P less than 0.01). These phenomena indicated that the utilization of Cu-Zn-SOD was increased due to excessive production of oxygen free radicals in multiple organ failure. PMID- 1596789 TI - [Changes in plasma prostaglandin F2, thromboxane B2 and 6-keto-prostaglandin F1 alpha contents in patients suffering from multiple system organ failure after burns]. PMID- 1596788 TI - [Effect of depletion of glucocorticoid receptor in the production of multiple organ failure during endotoxemia]. AB - Endotoxin (20 mg/kg B.W.) was injected intravenously to control (n = 12) and glucocorticoid receptor (GR) depletion rat model (n = 13, in which more than 80 percent of GR were blocked with a potent GR antagonist RU486). Four hours after injection of endotoxin, the changes in serum acid phosphatase (ACP) activity, phospholipase A2 (PLA2) activity and lipid peroxide (LPO) level were determined. The results showed that all of the indices were increased in the control rats after endotoxin injection (ACP 17.6 +/- 1.9 U/dL, PLA2 325.6 +/- 99.1 U, and LPO 6.0 +/- 0.4 nmol MDA.ml-1), but they were increased to even higher levels in the rats injected with both RU486 and endotoxin (ACP 30.1 +/- 7.6 U/dL, PLA2 633.7 +/ 70.6 U, and LPO 8.2 +/- 1.1 nmol MDP.ml-1). Furthermore, after presented multiple organ damage pathologically. These results suggested that the glucocorticoid insufficiency caused by the decrease of GR after severe trauma or shock may exacerbate the damage of endotoxin to the organs, so much so that glucocorticoid insufficiency might result in multiple organ failure. This article also discussed problem of glucocorticoid treatment. PMID- 1596790 TI - [Anatomical study and improvement of rotation-advancement method in repair of cleft lip]. AB - A new method of cleft lip repair, based on anatomical research of levator septi nasi and a peach-shaped musculocutaneous flap has been designed. The special features of this method are: 1. A small peach-shaped musculocutaneous flap is used as Millard's "c" flap, 2. all skin incisions are made on the edge of the cleft, 3. rotation-advancement repair is applied in the muscle layer. 32 patients have been followed for 6 years after the operation. PMID- 1596791 TI - [Experience with Furlow's palatoplasty and its preliminary result]. AB - The palatal muscle reconstruction has become an essential part of cleft palate repair. Sixty-one cases of various cleft palate and velopharyngeal incompetence after palatoplasty repair using the Furlow's double Z-plasty technique have been reported. A description of our surgical procedure along with the follow-up of 40 cases 1/2 to 1 year after operation demonstrate the advantages of the Furlow's palatoplasty. Our preliminary follow-up results show that the palatal competence rates are 90.5% in 21 cases of nasopharyngoscopic examination and 83.7% in 37 cases of still lateral X-ray radiograph. For maintaining adequate muscle reposition and soft palate pushback, the unilateral or bilateral mucoperiosteal flaps from hard palate are recommended in wider cleft palate. The design and some key points in the Furlow's palatoplasty are also discussed. PMID- 1596792 TI - [Reconstruction of traumatic auricular defect]. AB - Auricle is liable to be injured, owing to its position and structural conditions. Since 1977, 48 cases (52 ears) with traumatic auricular defect have been reconstructed by the use of different operative techniques. The results have been satisfactory for most of them. Loss of a major portion of the auricle or the entire ear itself can be reconstructed by use of framework of costal cartilage graft (autologous or homologous). The joint between remaining auricle and framework must be smooth and secure. Helical defect can be repaired by the use of advancement of auricular skin and cartilage, composite graft, free skin graft with subdermal vascular plexus or tube flap according to specific conditions. Unnecessary injury to tissue should be avoided during the operation. Earlobe defect can be repaired by the use of double subcutaneous pedicle skin flaps. The retroauricular subcutaneous pedicle composite flap including conchal cartilage and the pretragus subcutaneous skin flap are formed. They pass through respective subcutaneous tunnels to reach the defect area. The two flaps and remained auricular fresh edge are sutured together. A flat, new earlobe is reconstructed. The earlobe reconstructed by the use of this technique overcomes the unsightly "spherical earlobe". This technique is an ideal operative method. In brief, there are many forms of traumatic auricular defects. According to the size and extent of defect, careful planning is essential before the actual surgery takes place. PMID- 1596793 TI - [Changes in serum selenium in burn patients]. PMID- 1596794 TI - [Experimental study of gastrointestinal mucopathy after severe burns]. AB - Changes in gastrointestinal tract mucous membrane after serious burns were studied with light microscopy, transmission electron microscopy and scanning electron microscopy. The results showed that changes in the gastrointestinal tract mucous membrane included not only erosions and ulcers, but also mucoid necrosis and bacterial translocation. The injuries of the intestinal mucous membrane began from the apex of villi. There are epithelial necrosis, with desquamation and exposure of villi. The injuries are much more serious and extensive than that of gastric mucous membrane, especially in the jejunum. These results suggested that after serious burns, not only there were stress ulcers of the gastroduodenum, but the whole gastrointestinal tract was involved. PMID- 1596795 TI - [Effects of collagen and glucan on the healing of burn wounds in mice]. AB - The covering of the wound is one of the important measures in the burn treatment as well as in the control of infection and hypermetabolism. Skin transplantation is the major measure in covering the wound of III degree after escharotomy, while control of the infection was of primary importance in the treatment of II degree burn. Recent studies indicate that collagen provides good frame for extension of epidermis in wound healing, and glucan, an immunoregulator, promotes wound healing by the way of activating macrophages. In the present study, the effects of normal saline, 0.5% III type collagen and 5% glucan (0.4 ml/day for 10 days respectively) on the wound healing rate (healing area/initial wound area) was evaluated in the mice with 7% II degree burn. Biopsy specimens of the wound were examined under the microscope. Results showed that the healing rate with collagen and glucan was increased in the early stage of burn as compared with that of the saline control (P less than 0.05, P less than 0.01). The healing rate was even higher in the glucan group than that in the collagen group (P less than 0.05). Microscopic examination showed that the wound was covered by epidermis, proliferation of fibrous tissue under the epidermis, transformation of fibroblast to fibrocyte and collagenization in the early stage of burn in mice treated with collagen. The healing of the glucan group was also satisfactory, and it was characterized by more macrophages and active phagocytosis of hemosiderin. The above findings suggest that collagen and glucan can promote wound healing by different ways.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596796 TI - [Advance in the tempororetroauriculo-mastoid flap for reconstructing the facial area]. PMID- 1596797 TI - [Clinical study of the pathogeneses of multiple organ failure after burns]. AB - 51 burned patients with TBSA over 30% were studied prospectively. MOF developed in 17 of them. Postburn MOF occurred mainly in those with TBSA over 70%. Mortality of MOF was directly proportional to the number of organs involved. The incidence of pulmonary failure was the highest, and the highest mortality was attributed to renal failure. MOF occurring in the early stage was more related to burn shock, and those occurring in the late stage was predisposed mainly by infection. Oxygen free radicals play an important role in the genesis and development of postburn MOF. In this study, it was revealed that antiperoxidation ability declined, active oxygen was increased, and lipid peroxidation became excessive after the burn injury. It was also found that oxygen free radical mediated effects produced more serious damages in patients with MOF than those without, and also more in those died than the survivors. The hypoxanthine xanthine oxidase system was a significant source of oxygen radicals after the burn injury. There were also significant changes in plasma TXA2 and PGI2 levels postburn. The marked increase in TXA2/PGI2 ratio indicated imbalance between TXA2 and PGI2, which was correlated well with burn size and closely related to the development of postburn MOF. The excessive production of TXA2 might trigger or accelerate the formation of microaggregates and thromboxane, subsequently leading to visceral damages and failure. PMID- 1596798 TI - Childhood injuries. PMID- 1596799 TI - Childhood injuries. PMID- 1596800 TI - Ten years of AIDS. PMID- 1596801 TI - Ten years of AIDS. PMID- 1596802 TI - The ter Neuzen case: impossible standards. PMID- 1596803 TI - Is it time to close your hospital's ER? PMID- 1596804 TI - Funding in the asbestos debate. PMID- 1596805 TI - Near-death experience denied. PMID- 1596806 TI - Primum non nocere. PMID- 1596807 TI - Homeopathy--will its theory ever hold water? PMID- 1596808 TI - A guide to direct measures of patient satisfaction in clinical practice. Health Services Research Group. PMID- 1596809 TI - Large-scale use of an objective, structured clinical examination for licensing family physicians. AB - Since 1988 in Quebec the completion of a residency training program in family medicine or a specialty and of a comprehensive examination has been necessary to obtain a licence. An objective, structured clinical examination (OSCE) was designed by the Corporation professionnelle des medecins du Quebec and Quebec's four medical schools to evaluate the clinical competence of newly trained family physicians. The certification examination of the College of Family Physicians of Canada was added to the OSCE. More than 500 candidates have been assessed: 262 in the spring of 1990, 42 in the fall of 1990 and 235 in the spring of 1991. The spring session occurs in four centres, three offering it in French and one in English, and the fall session takes place in one bilingual centre. In each centre 25 standardized patients and 25 examiners are required on each day of the 2-day OSCE. The scores obtained by the candidates who completed the OSCE in the first three sessions showed a normal distribution. No more than 5% failed the OSCE, the pass level having been set at two standard deviations below the mean. Equivalence was shown among the OSCE tracks, and reliability coefficients of 0.644, 0.723 and 0.736 were obtained for the three sessions respectively. The overall success rate for the licensing examination was 92%. The integration of such a large-scale OSCE into a licensing examination and the results obtained show that assessment of clinical competence for licensing purposes is feasible. The Quebec experience may help other organizations that are developing OSCEs for summative purposes. PMID- 1596810 TI - Revised guidelines on ethical and legal considerations in anonymous unlinked HIV seroprevalence research. Federal Centre for AIDS Working Group on Anonymous Unlinked HIV Seroprevalence Research. PMID- 1596811 TI - Homeopathic treatment of plantar warts. AB - OBJECTIVE: To evaluate the efficacy of a homeopathic treatment of plantar warts. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Hospital-based family medicine unit. PATIENTS: Patients were recruited from the unit, through advertisements in the local media and through personal contacts with colleagues. Of the 853 people screened between December 1987 and January 1989, 174 met the eligibility criteria (age 6 to 59 years and presence of one or more plantar warts untreated during the previous 3 months) and agreed to participate; 162 (93%) completed the 18-week follow-up. INTERVENTIONS: The 6-week homeopathic treatment consisted of thuya 30 "centesimal hahnemannien" (CH) (one tube containing 200 pellets weekly), antimonium crudum 7 CH (5 pellets daily) and nitricum acidum 7 CH (one tube containing 200 pellets daily). The placebo pellets were identical to the treatment pellets in appearance and taste. MAIN OUTCOME MEASURE: The proportion of healed patients; a patient was considered healed if all of the warts had disappeared. MAIN RESULTS: The rates of healing at 6, 12 and 18 weeks were 4.8%, 13.4% and 20.0% respectively in the homeopathic treatment group and 4.6%, 13.1% and 24.4% in the placebo treatment group. CONCLUSION: The homeopathic treatment was no more effective than the placebo treatment of plantar warts. PMID- 1596812 TI - Congenital malaria in infants of asymptomatic women. PMID- 1596814 TI - Montreal: the convention city. 1929. PMID- 1596813 TI - Acylation-stimulating protein. PMID- 1596815 TI - Changes in criminal code will create more work for psychiatric facilities, MDs say. PMID- 1596816 TI - Maritime MDs, airlines team up to lower fares of patients travelling for treatment. PMID- 1596817 TI - There are easy ways to deal with difficult patients, MDs say. PMID- 1596818 TI - McGill-Haiti link proves educational for both student visitors and their hosts. PMID- 1596819 TI - When hype meets science: the asthma breakthrough that wasn't. PMID- 1596820 TI - The Toronto Free Hospital for Consumptive Poor. PMID- 1596821 TI - Women's health studies at Queen's bring feminist perspective to family practice. PMID- 1596822 TI - "We have to go back to healing the traditional way," native speakers tell Manitoba MDs. PMID- 1596823 TI - Reducing risk. PMID- 1596824 TI - Cold hard death, cold hard doctors. PMID- 1596825 TI - Cold hard death, cold hard doctors. PMID- 1596826 TI - Cold hard death, cold hard doctors. PMID- 1596827 TI - Cold hard death, cold hard doctors. PMID- 1596828 TI - Cold hard death, cold hard doctors. PMID- 1596829 TI - Cold hard death, cold hard doctors. PMID- 1596830 TI - Cold hard death, cold hard doctors. PMID- 1596831 TI - Cold hard death, cold hard doctors. PMID- 1596832 TI - Breaking bad news. PMID- 1596833 TI - Diet and calcium stones. PMID- 1596834 TI - Animal rights. PMID- 1596835 TI - Animal rights. PMID- 1596836 TI - Animal rights. PMID- 1596837 TI - Animal rights. PMID- 1596839 TI - The federal-provincial Canadian Heart Health Initiative. Canadian Heart Health Surveys Research Group. PMID- 1596838 TI - Animal rights. PMID- 1596840 TI - Toward integrated medical resource policies for Canada: 5. The roles and funding of academic medical centres. PMID- 1596841 TI - Spectrum of tuberculosis in patients with HIV infection in British Columbia: report of 40 cases. AB - OBJECTIVE: To review the clinical features, treatment and outcome of all known cases of tuberculosis in patients with human immunodeficiency virus (HIV) infection in British Columbia between 1984 and 1990. DESIGN: Retrospective case review. SETTING: Provincial tuberculosis registry and university-affiliated HIV clinic. PATIENTS: All people with HIV infection in whom active tuberculosis was diagnosed during the study period. RESULTS: All 40 patients identified were men; their mean age was 38 years. Of the subjects 30 (75%) were homosexual, 6 (15%) were homosexual and used intravenous drugs, 2 (5%) just used intravenous drugs, and 1 (2%) had had heterosexual contact with prostitutes; for the remaining subject the risk factor for HIV infection was not established. In all cases cultures of specimens from 15 body sources yielded Mycobacterium tuberculosis. Thirty-five of the patients had acquired immunodeficiency syndrome (AIDS), and five had HIV infection uncomplicated except for tuberculosis. In 28 (70%) of the cases no AIDS-defining disease had previously been diagnosed, and in 23 (58%) extrapulmonary tuberculosis represented the AIDS-defining disease. Symptoms at presentation included weight loss (in 80% of the cases), fever (in 75%), cough (in 70%) and night sweats (in 55%). The mean CD4 lymphocyte count was 0.2 x 10(9)/L (in 15 cases). Tuberculin skin test results were positive in 8 of 16 cases. The most striking radiologic finding was intrathoracic adenopathy. All except one of the 36 patients who received appropriate treatment responded favourably at first. Adverse reactions necessitating changes in treatment occurred in 12 (33%) of the cases. Relapse occurred after completion of therapy in two cases (one at 3 weeks and the other at 9 months after treatment was stopped). Tuberculosis was the cause of death in five cases. CONCLUSIONS: Tuberculosis in people with HIV infection commonly presents as extrapulmonary disease and precedes or coincides with other AIDS-defining opportunistic infections. In most cases tuberculosis is the AIDS-defining disease. Even though radiologic findings are often unusual physicians should suspect tuberculosis. A careful examination for evidence of disease at multiple sites should be done. The duration and choice of therapy must be adequate to avoid relapse. PMID- 1596842 TI - Family physicians' attitudes toward advance directives. AB - OBJECTIVE: To examine the attitudes toward, the experience with and the knowledge of advance directives of family physicians in Ontario. DESIGN: Cross-sectional survey. PARTICIPANTS: A questionnaire was mailed to 1000 family physicians, representing a random sample of one-third of the active members of the Ontario College of Family Physicians; 643 (64%) responded. RESULTS: In all, 86% of the physicians favoured the use of advance directives, but only 19% had ever discussed them with more than 10 patients. Most of the physicians agreed with statements supporting the use of advance directives and disagreed with statements opposing their use. Of the respondents 80% reported that they had never used a directive in managing an incompetent patient. Of the physicians who responded that they had such experience, over half said that they had not always followed the directions contained in the directive. The proportions of physicians who responded that certain patient groups should be offered the opportunity to complete an advance directive were 96% for terminally ill patients, 95% for chronically ill patients, 85% for people with human immunodeficiency virus infection, 77% for people over 65 years of age, 43% for all adults, 40% for people admitted to hospital on an elective basis and 33% for people admitted on an emergency basis. The proportions of physicians who felt that the following strategies would encourage them to offer advance directives to their patients were 92% for public education, 90% for professional education, 89% for legislation protecting physicians against liability when following a directive, 80% for legislation supporting the use of directives, 79% for hospital policy supporting the use of directives, 73% for reimbursement for time spent discussing directives with patients and 64% for hospital policy requiring that all patients be routinely offered the opportunity to complete a directive at the time of admission. CONCLUSIONS: Family physicians favour advance directives but use them infrequently. Most physicians support offering them to terminally or chronically ill patients but not to all patients at the time of admission to hospital. Although governments emphasize legislation, most physicians believe that public and professional education programs would be at least as likely as legislation to encourage them to offer advance directives to their patients. PMID- 1596843 TI - Cholera vaccination: a decision analysis. AB - OBJECTIVE: To examine the clinical impact and financial cost of a vaccination program for the prevention of cholera in North Americans travelling to endemic and epidemic regions by means of the principles of decision analysis and a decision tree as well as to illustrate the effect of case attack rates on the cost per case prevented by vaccination. DESIGN: Review of the scientific literature to establish the probabilities of each significant outcome as well as a decision analysis and partial economic evaluation. OUTCOME MEASURES: Clinical impact (attack rates for cholera among vaccinated and nonvaccinated travellers), rates of death associated with cholera and vaccine-associated adverse events (VAAEs), and the number of VAAEs and the vaccine cost per case prevented. MAIN RESULTS: On the basis of our assumptions (including a rate of one case of cholera per 500,000 journeys to endemic regions), to prevent one case of cholera a vaccination program would cost $28.67 million and be associated with 105 VAAEs. CONCLUSION: Routine vaccination of travellers to endemic areas cannot be recommended; however, for people travelling to regions with a high transmission rate vaccination should be considered. PMID- 1596845 TI - Phantom limb. 1941. PMID- 1596844 TI - Glandular tularemia with typhoidal features in a Manitoba child. PMID- 1596846 TI - Canadian heart health surveys: a profile of cardiovascular risk. Survey methods and data analysis. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To describe the methods used in nine provincial surveys carried out as part of the Canadian Heart Health Initiative. DESIGN: Population-based cross sectional surveys, following a core standardized protocol, implemented by provincial departments of health in collaboration with Health and Welfare Canada. Data were obtained through a home interview and a clinic visit. A standard manual of field operations and standardized training procedures were used in all provinces. SETTING: Nine Canadian provinces during the period 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registries in each province. Over 30% of the participants had post-secondary education. About 50% were 18 to 34 years old. OUTCOME MEASURES: Data on sociodemographic characteristics, hypertensive and diabetic status, knowledge and awareness of the causes and consequences of cardiovascular disease and two blood pressure measurements were obtained in a home interview. During a clinic visit, data were collected on height, weight (waist and hip circumferences in four provinces), two blood pressure measures and a blood sample. Total plasma cholesterol, triglycerides and high- and low-density lipoprotein cholesterol were measured in the Lipid Research Laboratory, University of Toronto and St. Michael's Hospital. MAIN RESULTS: Of the subjects invited to participate in the survey, 78% were interviewed, 69% attended the clinic and 64% provided a fasting specimen (8 hours or more). The response rates were slightly lower for men aged 18 to 34, for women aged 65 to 74 and for those with fewer years of education. Data from the provincial surveys (Ontario will complete the survey in 1992) are being compiled in the Canadian Heart Health Database. CONCLUSION: The process followed in the implementation of the provincial heart health surveys is a model of how provincial departments of health may carry out epidemiologic investigations in support of their mandate. The approach illustrates how a country-wide database can be built through partnerships among different levels of government. The use of community health nurses was instrumental in the efficient implementation of the surveys and in the realization of the relatively high rates of response attained. PMID- 1596847 TI - Plasma lipids and lipoproteins and the prevalence of risk for coronary heart disease in Canadian adults. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To report population reference values for blood lipids, to determine the prevalence of lipid risk factors and to assess their association with other risk factors. DESIGN: Population-based cross-sectional surveys. Survey participants were interviewed at home and provided a blood sample at a clinic. All blood lipid analyses were done in the Lipid Research Laboratory, University of Toronto. The laboratory is standardized in the National Heart, Lung Blood Institute-Centres for Disease Control Standardization Program. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 was selected from the health insurance registers for each province. Blood samples were obtained from 16,924 participants who had fasted 8 hours or more. OUTCOME MEASURES: Concentration of total plasma cholesterol, triglycerides and high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in blood samples from fasting participants. MAIN RESULTS: Of the study population, 46% had total plasma cholesterol levels above 5.2 mmol/L, 15% had LDL-cholesterol levels above 4.1 mmol/L, 15% had triglyceride levels above 2.3 mmol/L and 8% had HDL-cholesterol levels below 0.9 mmol/L. Total plasma cholesterol, LDL-cholesterol and triglyceride levels rose with age in men to a maximum in the 45-54 age group; in women there was little change with age up to ages 45 to 54, at which time the level of each of these lipids increased appreciably. The age-standardized prevalence of obesity was positively associated with elevation of total plasma cholesterol. CONCLUSION: The results suggest the need for a multifactorial approach in health promotion efforts to lower blood cholesterol levels and reduce other risk factors in the population. A considerable number of adults were found to be at risk at all ages in both sexes. In the short term, men aged 34 and older and women aged 45 and older might benefit most from prevention programs. PMID- 1596848 TI - Smoking prevalence and associated risk factors in Canadian adults. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To describe the prevalence and patterns of smoking among Canadian adults, the relation of smoking to other cardiovascular disease risk factors and the awareness of the causes of heart disease. DESIGN: Population-based cross sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 was selected from the health insurance registries in each province. Of these, 20,585 completed a questionnaire on smoking habits during a home interview. MAIN RESULTS: Approximately 29% of the Canadian population 18 years of age and over were regular cigarette smokers, and over 13% of regular smokers smoked more than 25 cigarettes per day. The proportion of women who had never smoked was higher (37%) than men (24%), except for young women aged 18 to 24. For all participants, there was a lower prevalence of high blood pressure and overweight among smokers than non-smokers. The prevalence of sedentary lifestyle, diabetes and elevated blood cholesterol was positively associated with smoking. The proportion of subjects who identified smoking as a cause of heart disease was higher among smokers, and over 90% believe that heart disease is preventable. CONCLUSION: Because smoking is positively associated with other cardiovascular risk factors, multifactorial and comprehensive approaches are needed in the implementation of cardiovascular disease prevention programs. Knowledge regarding the heart health hazards of smoking is high even among smokers. Motivational approaches that go beyond health risk messages are needed in cessation programs. PMID- 1596849 TI - Prevalence, control and awareness of high blood pressure among Canadian adults. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To estimate the prevalence and distribution of elevated blood pressure (BP) among Canadian adults and to determine the level of control, treatment, awareness and prevalence of other risk factors among adults with high BP. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registers in each province. For 20,582 subjects, BP was measured at least twice. Nurses administered a standard questionnaire and recorded two BP measurements using a standardized technique. Two further BP readings, anthropometric measurements and a blood specimen for lipid analysis were obtained from those subjects who attended a clinic. OUTCOME MEASURES: Mean values of systolic and diastolic BP, prevalence of elevated BP using different criteria, and prevalence of smoking, elevated blood cholesterol, body mass index, physical activity and presence of diabetes by high BP status are reported. MAIN RESULTS: Sixteen percent of men and 13% of women had diastolic BP of 90 mm Hg or greater or were on treatment (or both). About 26% of these subjects were unaware of their hypertension, 42% were being treated and their condition controlled, 16% were treated and not controlled, and 16% were neither treated nor controlled. Use of non-pharmacologic treatment of high BP with or without medication was low (22%). Hypertensive subjects showed a higher prevalence of elevated total cholesterol, high body mass index, diabetes and sedentary lifestyle than normotensive subjects. Most people with elevated BP were in the 90 to 95 mm Hg range for diastolic pressure and 140 to 160 mm Hg range for systolic pressure. Prevalence of high isolated systolic BP sharply increased in men (40%) and women (49%) 65 to 74 years old. CONCLUSIONS: The relatively low level of control of elevated BP calls for population and individual strategies, stressing a non-pharmacologic approach and addressing isolated systolic hypertension in the elderly. PMID- 1596852 TI - Canadian doctors may want to take this Popcorn with a grain of salt. PMID- 1596850 TI - Obesity and its relation to cardiovascular disease risk factors in Canadian adults. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To describe the distribution of weight and abdominal obesity among Canadian adults and to determine the association of obesity with other risk factors for cardiovascular disease. DESIGN: Population-based cross-sectional surveys. Survey nurses administered a standard questionnaire and recorded two blood pressure measurements during a home visit. At a subsequent visit to a survey clinic two further blood pressure readings were made, anthropometric measurements recorded and a blood specimen taken for plasma lipid determination. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women aged 18 to 74 years was selected from the health insurance registration files of each province. Anthropometry was performed on 17,858 subjects. OUTCOME MEASURES: Body mass index (BMI), ratio of waist to hip circumference (WHR), mean plasma lipid levels, prevalence of high blood pressure (diastolic greater than or equal to 90 mm Hg or patient on treatment) and self reported diabetes mellitus. MAIN RESULTS: The prevalence of obesity (BMI greater than or equal to 27) increased with age and was greater in men (35%) than in women (27%). Abdominal obesity was likewise higher in men and increased with both age and BMI. The prevalence of high blood pressure was greater in those with higher BMI, especially in those with a high WHR. Although total plasma cholesterol levels increased only modestly with BMI, levels of low density lipoprotein (LDL) cholesterol and triglycerides and the ratio of total cholesterol to high density lipoprotein (HDL) cholesterol increased steadily, while HDL-cholesterol decreased consistently with increasing BMI. High total cholesterol levels (greater than or equal to 5.2 mmol/L) were more prevalent among people with high BMI, especially those with a high WHR. The prevalence of diabetes increased with BMI among those 35 years or older, especially those with abdominal obesity. About half of men and two-thirds of women who were obese were trying to lose weight. CONCLUSION: Obesity remains common among Canadian adults. There is a need for broad-based programs that facilitate healthy eating and activity patterns for all age groups. Health professionals should incorporate measurement of BMI and WHR into their routine examinations of patients to enhance their evaluation of health risk. PMID- 1596851 TI - Multiple cardiovascular disease risk factors in Canadian adults. Canadian Heart Health Surveys Research Group. AB - OBJECTIVE: To estimate the prevalence and distribution of the coexistence of major cardiovascular disease (CVD) risk factors among Canadian adults. DESIGN: Population-based cross-sectional surveys. SETTING: Nine Canadian provinces, from 1986 to 1990. PARTICIPANTS: A probability sample of 26,293 men and women, aged 18 to 74 years, was selected from provincial health insurance registries. For 20,582 of these participants, at least two blood pressure (BP) measurements were taken using a standardized technique. At a subsequent visit to a clinic, two additional BP readings, anthropometric measurements and a blood specimen for plasma lipid analysis were obtained. OUTCOME MEASURES: The percentage distribution of subjects by number of major risk factors (smoking, high BP and elevated blood cholesterol level) and by concomitant factors (body mass index [BMI], ratio of waist to hip circumference [WHR], physical activity, diabetes, awareness of CVD risk factors and education). MAIN RESULTS: Sixty-four percent of men and 63% of women had one or more of the major risk factors. Prevalence increased with age to reach 80% in men and 89% in women aged 65 to 74 years. Prevalence of two or three risk factors was highest among men in the 45-54 age group (34%) and in women in the 65-74 age group (37%). The most common associations were between smoking and high blood cholesterol level (10%) and between high BP and high blood cholesterol level (8%). Prevalence of high BP and elevated blood cholesterol, alone or in combination, increased with BMI and WHR. Smoking, elevated blood cholesterol, BMI and prevalence of one or more risk factors increased with lower level of education. Less than 48% of participants mentioned any single major risk factor as a cause of heart disease. Awareness was lowest in the group with fewest years of education. CONCLUSION: The findings of this study call for an approach to reduce CVD that stresses collaboration of the different health sectors to reach both the population as a whole and the individuals at high risk. PMID- 1596853 TI - Phantom limbs still a ghostly phenomenon. PMID- 1596854 TI - After I looked south, the north didn't look so bad. PMID- 1596855 TI - Lack of health insurance takes tragic toll among US patients. PMID- 1596856 TI - The US should be wary of Canada's health care system. PMID- 1596857 TI - New MCC qualifying exam causing confusion and anxiety, interns and residents say. PMID- 1596858 TI - Abortion rights issue continues to divide east and west Germany. PMID- 1596859 TI - Sick hospital, sick doctor: Halifax hospital tries to cope with "environmental illness". PMID- 1596860 TI - MD launches study to determine amount of job-related hearing loss in military. PMID- 1596861 TI - AIDS and the law: do courts have a place in the bedrooms of the nation? PMID- 1596862 TI - Practical approach to psychosomatic illness in children can save time and heartache, MD says. PMID- 1596863 TI - Distribution of the Bowman Birk protease inhibitor in mice following oral administration. AB - In this study, the distribution of the soybean-derived Bowman Birk inhibitor (BBI) in mice was examined. Mice received [125I]BBI by oral gavage and three hours later, the mice were sacrificed, the organs of interest were carefully removed and the distribution of the inhibitor was determined. The bulk of labeled BBI was present in the luminal contents of the small and large bowel, urine and feces. Significant amounts of label were also observed in the serum, esophagus, stomach and intestine, kidney, liver and lung. Analysis of tissue homogenates by gel filtration chromatography revealed that the radioactivity eluted from the column at the same position as the BBI standard indicating that the iodinated BBI was still intact. The chromatographically purified BBI was able to inhibit chymotrypsin indicating that functional protease inhibitory activity was present. These results indicate that the BBI becomes widely distributed in mice 3 h after oral administration and that intact protease inhibitor is present in internal organs. PMID- 1596864 TI - Comparative carcinogenicity of 4-aminobiphenyl and the food pyrolysates, Glu-P-1, IQ, PhIP, and MeIQx in the neonatal B6C3F1 male mouse. AB - The tumorigenic activities of four representative heterocyclic amine food pyrolysates, 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino 3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8 dimethylimidazo[4,5f]quinoxaline (MeIQx), and 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP), were assessed in the neonatal male B6C3F1 mouse and were compared with that of the potent human carcinogen, 4-amino biphenyl (4-ABP). These aromatic amines were administered by i.p. injection at two dose levels on days 1, 8, and 15 after birth; and the incidence of tumors was examined at 8 and 12 months. Glu-P-1, IQ, PhIP, MeIQx, and 4-ABP each induced a significant incidence of hepatic adenomas, as compared to the solvent-treated (DMSO) control. Hepatocellular carcinomas were also observed with 4-ABP, SO, and MeIQx. Overall tumorigenicity was in the order: 4-ABP greater than Glu-P-1 greater than IQ approximately PhIP greater than MeIQx greater than DMSO. In the neonatal B6C3F1 mouse, these heterocyclic aromatic amines showed potent tumorigenicity after 8 and 12 months at total doses that were 5-10,000-fold less than those employed in standard chronic bioassays. PMID- 1596865 TI - Elevated serum manganese superoxide dismutase in acute leukemias. AB - We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease. PMID- 1596866 TI - Cytotoxic effect of plant polyphenols and fat-soluble vitamins on malignant human cultured cells. AB - In vitro studies showed that several flavonoids, tannic acid, gallic acid and fat soluble vitamins inhibited HeLa and Raji lymphoma cell growth. The inhibition trend exhibited by these compounds was similar for both cell lines, and their growth was inhibited dose dependently. Butein, (10 microM), the most potent anti proliferative agent, exerted 30% growth inhibition and was more effective on HeLa cells. Retinol (100 microM) inhibited cell proliferation completely. Tannic acid was twice as potent as its monomer gallic acid. From structure-activity consideration, the C2,3-double bond of the flavonoid molecule was important for activity. Flavonoid aglycones were more effective than their corresponding glycosides in suppressing cell growth. PMID- 1596867 TI - Inhibition of penta-acetyl geniposide on AFB1-induced genotoxicity in C3H10T1/2 cells. AB - A new compound, penta-acetyl geniposide ((Ac)5-GP), was obtained from modified extract of Gardenia fructus (San-Jee-Chee in Chinese). The structure of the compound was identified as 1-(beta-D-2',3',4',6'-tetraacetyl-glucopyrannosyloxyl) 1,4a, 5,7a-tetrahydro-7-(acetomethyl)-cyclopentapyran-4-carboxylic acid methyl ester, according to the spectral data. The inhibitory effects of (Ac)5-GP on aflatoxin B1 (AFB1)-induced cytotoxicity and DNA damage were studied. In the investigation of the inhibitory effect of (Ac)5-GP on AFB1-cytotoxicity, the plating efficiency of C3H10T1/2 cells in S-9 activation system was increased. In addition, (Ac)5-GP inhibited the DNA damage of AFB1-treated C3H10T1/2 cells, and it interfered with the inhibitory effect of DNA synthesis caused by AFB1. These results suggest that the reduced DNA damage and the increased DNA synthesis from cultured C3H10T1/2 cells are important mechanisms for the inhibition of AFB1 cytotoxicity by (Ac)5-GP. PMID- 1596868 TI - Interleukin-3 dependent c-myc protein expression during the cell cycle of murine mast cells. AB - Aim of the study was to evaluate the relationship between the mitogenic stimulus interleukin-3 to normal murine mast cells and the cell cycle dependent expression of the nuclear c-myc protein. In order to do that on a cell by cell basis, we measured the nuclear c-myc protein simultaneously by flow cytometry, via specific monoclonal antibodies, and the DNA content via the intercalating dye propidium iodide. When cells were deprived from interleukin-3 (IL-3), proliferation was inhibited and the majority of cells arrested in early G1 (G1A, characterized by low c-myc content). Readdition of IL-3 resulted in a slow transition of cells from G1A to late G1 (G1B, at higher c-myc content) before DNA synthesis started. G1A cells with low c-myc content do not undertake DNA synthesis. Using a stathmokinetic methodology we confirmed that the G1A cells are early postmitotic G1 phase cells. The low content of c-myc within these cells appears a direct consequence of reduced c-myc levels during mitosis. Cumulatively, the data suggest that c-myc protein levels of murine mast cells fall at mitosis and that these levels must rise before cells can traverse the G1 phase. Our data are compatible with a model in which c-myc protein content of G1 phase cells has to reach a critical threshold before the cells can move further into the cell cycle. PMID- 1596869 TI - Cholecystokinin inhibits DNA alkylation induced by N-nitrosobis (2 oxopropyl)amine (BOP) in hamster pancreas. AB - Cholecystokinin (CCK) inhibits pancreatic cancer but not hepatic tumor induction by N-nitrosobis (2-oxopropyl) amine (BOP) in hamsters when administered with or shortly before BOP. In this study, we evaluated the capability of sulfated CCK-8 to inhibit DNA alkylation in the hamster pancreas. We examined the pattern of O6 methylguanine (G6-Me) and N7-methylguanine (G7-Me) in pancreatic ductal, acinar and liver tissues from Syrian hamsters treated with a single dose of BOP (20 mg/kg s.c.) and with five s.c. injections of CCK-8 (200 pM/kg, 30 min apart). The first CCK injection was given either 90 min before, or together, or 3 h after POP administration. The amount of G6-Me in liver DNA did not differ significantly. We observed a decrease of G7-Me in the liver of the group treated with CCK together with POP as compared to POP alone (P less than 0.005). Lower amounts of G6-Me were found in ductal preparations (P less than 0.01) of the animals treated with CCK before POP as compared to POP alone. CCK also modified the pattern of alkylation in the acinar tissue, but without a clear relationship with the timing of administration. The results suggest that the inhibitory effect of CCK-8 on pancreatic carcinogenicity of BOP could be related to its capability to modify DNA alkylation by yet unknown mechanisms. PMID- 1596870 TI - Use of IL-2 gene transfer in local immunotherapy of cancer. AB - Insertion of functional interleukin-2 (IL-2) gene into a plasmacytoma cell line X63-Ag8.653 substantially reduced tumorigenicity of the resulting cloned cells, designated as X63-m-IL-2. Peritumoral administration of the X63-m-IL-2 cells, producing constitutively large quantities of IL-2, resulted in regressions of established X63-Ag8.653 plasmacytomas growing in the peritoneal cavity of syngeneic mice. In vitro activation of BALB/c spleen cells by co-culture with X63 m-IL-2 cells or their supernatants gave rise to cytotoxic lymphocytes with lymphokine-activated killer (LAK) activity against syngeneic X63-Ag8.653 plasmacytoma and other tumor targets. In contrast, peritumoral administration of X63-Ag8.653 cells carrying an inserted interleukin-4 (IL-4) gene (designated X63 m-IL-4 cells) and producing constitutively large quantities of IL-4 did not result in a therapeutic effect. Moreover, the admixture of the X63-m-IL-4 and X63 m-IL-2 cells substantially diminished the X63-m-IL-2 cell-mediated therapeutic effect. Similarly, IL-4-containing supernatants generated from X63-m-IL-4 cell cultures substantially diminished LAK activation by X63-m-IL-2 cell produced supernatants. PMID- 1596871 TI - Induction of proliferin gene expression by diverse chemical agents that promote morphological transformation in C3H/10T1/2 cultures. AB - Anthralin, iodoacetic acid, BHT, Tween 60 and TPA induced cytoplasmic accumulation of transcripts of the proliferin gene family at or near effective concentrations for promotion of morphological transformation of C3H/10T1/2 cells. Conversely, non-promoters (4-alpha-phorbol, formic acid and methanol) were ineffective inducers. Compounds likely to promote transformation (nickel sulphate, benzyl peroxide and t-butyl hydroperoxide) were also effective and apparently selective, proliferin inducers in C3H/10T1/2 and primary murine fibroblasts. Proliferin induction may be a useful molecular marker to predict chemically-induced promotion of morphological transformation in C3H/10T1/2 cells. PMID- 1596872 TI - Linoleate produces remission in canine mycosis fungoides. AB - Linoleic acid (LA) administered orally as safflower oil (SFO), which is 76% LA, produced remission in 6 out of 8 dogs with mycosis fungoides (MF). Following each feeding of SFO on 5 successive days to a normal dog peak plasma levels of non esterified (free) LA in excess of 200 microM were observed. No clinical toxicity was observed from the SFO feedings in the normal or MF animals at the levels of SFO (3 ml/kg) used in these studies. However, a marked rise in white blood cells (WBC) and lymphocytes and a marked transient drop in the serum glutamine transaminases SGOT and SGPT was noted both in the normal and MF animals. These effects of LA may be significant for the remission of MF. PMID- 1596873 TI - Lack of effectiveness of antiestrogens RU 39,411 or keoxifene in the prevention of estrogen-induced tumors in Syrian hamsters. AB - As part of a search for an effective and safe antiestrogen to be used as adjunct therapy in the treatment of breast cancer, we examined the potential of RU 39,411 and keoxifene to inhibit the incidence of estradiol-induced kidney tumors in Syrian hamsters. Groups of 10 hamsters were chronically treated with implants of either keoxifene, RU 39,411, estradiol plus keoxifene, or estradiol plus RU 39,411 for 8 months. Five hamsters received only estradiol and 5 control animals remained untreated. There was a 100% kidney tumor incidence in estradiol-treated hamsters, which was not statistically different from that in animals co-treated with estradiol plus keoxifene (3 of 4 hamsters with tumors) or estradiol plus RU 39,411 (7 of 8 hamsters with tumors). Rodents treated only with antiestrogen remained tumor free. In addition to kidney tumors, testicular cancer was also found in animals cotreated with either estradiol plus keoxifene (2 of 4 hamsters with tumors) or estradiol plus RU 39,411 (3 of 8 hamsters with tumors). Two animals of this latter group also developed liver tumors. Testicular or liver neoplasms were not observed in hamsters implanted only with estradiol or only with antiestrogen. The lack of inhibition of estrogen-induced carcinogenesis in hamsters by RU 39,411 or keoxifene suggests that these two antiestrogens are not as effective as previously tested substances in inhibiting the appearance of this cancer. However, their concentrations were sufficient to induce, in combination with estradiol, the development of testicular tumors in these hamsters. PMID- 1596874 TI - Modulation of laminin synthesis in human neuroblastoma cells during retinoic acid induced differentiation. AB - A comparable pattern of morphological neuronal differentiation was induced in the human neuroblastoma cell line SMS-KCNR by treatment with either retinoic acid (RA) or exogenous laminin (LM). LM expression and synthesis by SMS-KCNR was increased upon RA treatment which involved the cell bound, rather than the secreted protein. These data suggest an involvement of LM in the neuroblastoma differentiation process manifested both as an ability of LM to induce a morphological neuronal differentiation and as a selective control on LM metabolism during RA induced neuronal differentiation. PMID- 1596875 TI - Initiation and post-initiation chemopreventive effects of diallyl sulfide in esophageal carcinogenesis. AB - Diallyl sulfide (DAS), one of a number of organosulfur compounds accounting for the flavor and smell associated with garlic, has been shown to inhibit a number of chemically induced forms of cancer. In this study, DAS was examined for its chemopreventive effects in both the initiation and post-initiation phases of nitrosomethylbenzylamine-induced esophageal carcinogenesis in the Sprague-Dawley rat. Although highly inhibitory during initiation, DAS is ineffective when given after the carcinogen. DAS, though not effective as a preventive in post initiation, was not found to promote esophageal carcinogenesis. PMID- 1596876 TI - Decreased interleukin-2 beta-chain receptor expression by interleukin-4 on LGL: influence on the IL-2 induced cytotoxicity and proliferation. AB - Addition of increasing amounts of interleukin-4 (IL-4) to large granular lymphocytes (LGL) had a selective downregulative effect on the interleukin-2 beta chain (p70) receptor expression. A 40% inhibition of the p70 expression compared to untreated cells was already observed after a 24-h incubation with IL-4. This decrease in p70 receptor expression had a marked suppressive effect on their proliferative response to IL-2. In addition, LGL cultured in the presence of both IL-2 and IL-4 substantially decreased the cytotoxic activity against the erythroleukemia cell line K562. Our data therefore indicate an important regulative role for IL-4 on the LAK-generation. PMID- 1596877 TI - Genotoxic effect of smoke-dried meat extract in Swiss albino mice using sperm head shape abnormality test. AB - The genotoxic effect of an extract of smoke-dried meat was assayed by employing in vivo sperm head shape abnormality. A significant dose responsive mutagenic effect was observed using the sperm head shape abnormality test. The result indicates that higher doses i.e., 100 and 200 mg/kg body wt. of smoke meat extract, significantly induced sperm head shape abnormality as compared to lower doses i.e., 20 mg/kg body wt. and control. PMID- 1596878 TI - Protective effect on cisplatin hematotoxicity by procaine hydrochloride. AB - The ability of procaine hydrochloride (P.HCl) to modulate the effects of cisplatin (DDP) on pluripotent (CFU-S) and committed (CFU-GM) murine hemopoietic stem cells was investigated. DBA/2NCrlBRF1 mice received DDP alone (10 and 16 mg/kg body wt. single i.p. injection) or in combination with P.HCl (40 mg/kg body wt. single i.p. injection). Hemopoietic progenitor cell (HPC) time survival curves were determined up to 14 days following treatment. The simultaneous administration of the lower DDP dose together with P.HCl greatly reduced the hemotoxicity of the antitumoral drug, while this protection was not significant with the higher DDP dose. These results support a role for P.HCl in protecting against DDP hematological toxicity. PMID- 1596879 TI - Antiproliferative properties of aminosteroid antioxidants on cultured cancer cells. AB - The antiproliferative properties of three 21-aminosteroid antioxidants (lazaroids), 21-[4-[5,6-bis(diethylamino)-2-pyridinyl]-1- piperazinyl]-16 alpha methylpregna-1,4,9(11)triene-3,20-dione, hydrochloride (U74500A), 21-[4-(2,6-di-1 pyrrolidinyl-4-pyrimidinyl)-1-piper- azinyl]-pregna-1,4,9(11)-triene-3,20-dione, monomethanesulfonate (U74389F), 2H-1-benzopyran-6-ol, 2-[[4-[3-(ethylamino)-2 pyridinyl]-1-piperzinyl]methyl]-3,4- dihydro-2,5,7,8-tetramethyl-, (Z)-2-buten dioate (U78518F), on human breast cancer cells are described. U74500A inhibited cell proliferation in a dose-dependent manner with IC50 values of approximately 1.7 and 1.2 microM when cells were exposed to the drug for 3 and 5 days, respectively. The non-steroid antioxidants, alpha-tocopherol and nordihydroguaiaretic acid, showed weak or no activity at the same dose range. All three lazaroids inhibited, dose dependently, the proliferation of mouse lymphocytes but only at IC50 values ranging between 20-30 microM. The specificity of action was studied by including other steroids: progesterone, testosterone and hydrocortisone. Both sex hormones stimulated cell proliferation at low (less than 10(-5) M) concentrations but inhibited at higher doses with IC50 values of 26 (progesterone) and 80 (testosterone) microM. Hydrocortisone (IC50 0.17 microM), on the other hand, inhibited cell proliferation by 70% over a wide range of doses. Human breast cancer cells appear to have a greater sensitivity than the mouse lymphocytes to lazaroids. The antiproliferative effects of lazaroids in cancer cells may be, at least in part, due to an interaction with glucocorticoid receptors. PMID- 1596881 TI - Two-step carcinogenesis induced by neonatal exposure to 5-bromo-2'- deoxyuridine and subsequent administration of urethan in BALB/c mice. AB - Male and female BALB/c mice were exposed to subcutaneous injections of 1 mg 5 bromo-2'-deoxyuridine (BrdUrd) at the 1st, 3rd and 7th days after their birth and/or starting from 3 months of age, and every third day were given 5 intraperitoneal injections of 0.1 ml of 5% solution of urethan. Treatment with BrdUrd alone followed by delay in mice development, reduction of the body and liver weight did not significantly increase the incidence of tumor development at 9 months of age. Exposure to both BrdUrd and urethan lead to summation or potentiation of their effects, manifested in increased lung adenoma incidence and their number per tumor-bearing mouse. In males, which received BrdUrd and urethan a significant increase in lung adenocarcinomas and haemoblastosis was observed in comparison to other groups. It was suggested that genome instability induced by exposure to BrdUrd facilitate the realization of the carcinogenic effect of urethan. PMID- 1596880 TI - Antitumor activity of a novel nucleoside, 2'-C-cyano-2'-deoxy-1-beta-D arabinofuranosylcytosine (CNDAC) against murine and human tumors. AB - The antitumor effects of 2'-C-cyano-2'-deoxy-1-beta-D- arabinofuranosylcytosine (CN-DAC), a synthetic 1-beta-D-arabinofuranosyl-cytosine (ara-C) derivative, were examined and compared with that of ara-C in murine tumors and in various human tumors using three different chemosensitivity tests. CNDAC extended the life span of mice bearing P388 leukemia. CNDAC had a unique in vitro antitumor spectrum for human cancers different from that of ara-C. Compared with ara-C, CNDAC was more effective in 10 human tumors (2 lung, 4 stomach and 4 osteosarcoma), equal in 2 tumors (lung and fibrosarcoma) and less potent in 11 tumors (4 lung, 4 osteosarcoma, bladder, renal and epidermoid). Characteristically CNDAC showed excellent activities against tumors, refractory to ara-C, such as HT-1080 human fibrosarcoma implanted in chick embryos or athymic mice, although its cytotoxicity against HT-1080 was almost equal to that of ara-C. Thus, CNDAC is an interesting and promising agent that should be considered for further detailed preclinical evaluation. PMID- 1596882 TI - Selective in vivo localization of daunorubicin small unilamellar vesicles in solid tumors. AB - Small unilamellar vesicles (SUVs), consisting of highly purified distearoyl phosphatidylcholine and cholesterol (2:1 mol ratio) selectively increased the delivery of entrapped daunorubicin to solid tumors in vivo. When measured against free drug, SUV-entrapped daunorubicin produced a nearly 10-fold increase in tumor uptake and efficacy when used to treat a murine lymphosarcoma model (P-1798). In a second murine solid tumor model, MA16C mammary adenocarcinoma, the median survival time for daunorubicin SUV treatment at 2 mg/kg (72 days) was equivalent to the median survival time for the free drug optimal dose, 20 mg/kg (70 days), again indicating a 10-fold increased therapeutic efficacy. When compared at maximum efficacious doses in the MA16C model, the proportion of long-term survivors was greater with daunorubicin SUVs: 10 long-term survivors of 10 mice treated with daunorubicin SUVs at 25 mg/kg versus 4 long-term survivors of 10 mice treated with free drug at 20 mg/kg. The lowest toxic doses for MA16C tumor bearing animals (treatment median survival times less than controls) were 25 mg/kg for free drug and 40 mg/kg for daunorubicin SUVs. The demonstration of enhanced antineoplastic activity and an increased tolerance for daunorubicin suggests that this specific SUV composition may be an effective delivery system for a wide range of chemotherapeutic agents in the treatment of solid tumors. PMID- 1596883 TI - An unmodified anticarcinoma antibody, BR96, localizes to and inhibits the outgrowth of human tumors in nude mice. AB - The antitumor effects of an unmodified murine monoclonal antibody, BR96, were examined in nude mice bearing human lung adenocarcinoma xenografts. BR96, a murine IgG3 that internalizes and is cytotoxic to cells expressing the antigen in vitro, also elicits strong antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity effector functions. Its in vivo antitumor effects were compared with those of its F(ab')2 fragments, a mouse-human chimeric form, and an IgG1 class switched variant of the original (IgG3) BR96. Antitumor effects were observed with antigen-positive tumor lines (but not with tumors which did not bind with BR96) and correlated with the levels of antigen expression as detected in vitro. The chimeric form of BR96 gave the strongest antitumor effects, followed by the murine IgG3, while limited effects were seen with the IgG1 and with F(ab')2 fragments of BR96, indicating that Fc-dependent host effector functions are primarily responsible for its in vivo activity. The antitumor effects observed were modest unless the antibody treatment was started on the day following tumor grafting. PMID- 1596884 TI - Effect of thrombin treatment of tumor cells on adhesion of tumor cells to platelets in vitro and tumor metastasis in vivo. AB - Seven different tumor cell lines (human melanoma SK MEL 28; hamster melanoma HM29; murine melanomas B16F10 and amelanotic melanoma B16a; human colon carcinoma HCT8; murine colon carcinoma CT26; and murine Lewis lung carcinoma) were treated with thrombin at 0.5-1 unit/ml and examined for their ability to bind to adherent platelets; HM29 was studied for its ability to bind to fibronectin and von Willebrand factor; CT26, B16F1, B16F10, and B16a were studied for their ability to form pulmonary metastasis after i.v. injection of thrombin-treated tumor cells; CT26 was studied for its ability to grow s.c. Five of 7 thrombin-treated tumor cell lines increased their adhesion to adherent platelets 2-to 3-fold. HM29 increased its adherence to fibronectin and von Willebrand factor 2- to 3-fold. CT26, B16F1, B16F10, and B16a increased experimental pulmonary metastasis 10- to 156-fold. Thrombin-treated CT26 cells demonstrated 2-fold greater growth in vivo after s.c. injection. The mechanism of enhanced adhesion of thrombin-treated tumor cells to platelets required the platelet integrin GPIIb-GPIIIa since it could be inhibited by agents known to block adhesion of ligands to GPIIb-GPIIIa (monoclonal antibody 10E5, tetrapeptide RGDS, disintegrin Albolabrin); as well as a "GPIIb-GPIIIa-like" structure on tumor cells since it could be inhibited by treatment of thrombin-treated tumor cells with 10E5 and RGDS. The thrombin effect on tumor cells was optimum at 1 h of incubation with thrombin, did not require active thrombin on the tumor cell surface, and did not require protein synthesis (not inhibited by cycloheximide). Thus, thrombin-treated tumor cells markedly enhance pulmonary metastasis. It is suggested that this may be secondary to thrombin-induced enhanced adhesion as well as growth of tumor cells. PMID- 1596885 TI - Placental transfer of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone instilled intratracheally in Syrian golden hamsters. AB - The tobacco-specific N-nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1- butanone (NNK) is a potent tumorigen in adult Syrian golden hamsters and an active transplacental carcinogen in this species. In this study, we have investigated the biodistribution and metabolism of NNK in maternal and fetal hamster tissues as a function of the dose and the time after NNK treatment. Hamsters on day 15 of gestation were instilled intratracheally with single doses (0.05-100 mg/kg) of [5-3H]NNK and sacrificed 30 min later or treated with a single dose (25 mg/kg) of [5-3H]NNK and sacrificed at various times (5-360 min) after treatment. Total radioactivity was quantified in maternal tissues (liver, lung, kidney, placenta, and stomach), in whole fetus and in fetal tissues (liver and lung). NNK and its metabolites were extracted from selected tissues (maternal plasma, amniotic fluid, fetal liver, and lung) and assayed by high-performance liquid chromatography-scintigraphy. Thirty min after treatment, radioactivity associated with NNK and its metabolites showed similar widespread tissue distribution patterns at all doses, with a linear dose relationship observed in whole fetus and fetal tissues. NNK levels detected in maternal plasma, amniotic fluid, fetal liver, and lung were also related linearly to dose. At high doses (25 mg/kg or more) of NNK, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol was the major metabolite detected in maternal plasma. Pyridine N-oxidation of NNK predominated at the lowest doses (0.05 and 0.5 mg NNK/kg). The toxicokinetics of NNK demonstrated that this carcinogen is rapidly absorbed from the maternal lung (less than 5 min), metabolized mainly to 4-(methylnitrosamino)-1- (3-pyridyl)-1 butanol, and quickly distributed into the maternal-fetal compartment. Both NNK and its main metabolite 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanol were eliminated slowly from the amniotic fluid, with levels still detectable up to 6 h after NNK treatment. These results demonstrated that NNK instilled intratracheally in pregnant hamsters crossed the placental barrier even at low doses. Moreover, NNK quickly reached fetal tissues and amniotic fluid and was eliminated slowly from these tissues, resulting in an extended exposure of the fetus to this tobacco-specific carcinogen. PMID- 1596886 TI - Expression of glutathione transferase pi as a predictor for treatment results at different stages of acute nonlymphoblastic leukemia. AB - The expression of glutathione transferase pi (GST pi) was studied in leukemic cells from 60 patients with acute nonlymphoblastic leukemia at diagnosis and at progressing stages of the disease. A polyclonal rabbit antibody to human placental GST pi coupled with peroxidase antiperoxidase staining was used for immunodetection of GST pi on sections of routinely fixed bone marrow clots. All patients had received induction therapy based on an anthracycline and a standard dose of ara-C. The expression of GST pi at diagnosis was significantly correlated with response to induction therapy, duration of first remission, and overall survival. Twenty-nine of 36 samples of bone marrow from patients that entered complete remission (CR) following primary induction therapy showed a low expression, whereas nine of 16 sections from patients with resistant disease showed a high expression of GST pi (P less than or equal to 0.03). Of 40 sections that showed a low expression of GST pi, 29 (73%) were taken from patients that achieved a CR, whereas 12 of 19 sections that showed a high expression of the enzyme were from patients with resistant disease or that entered CR only after additional therapy (P less than or equal to 0.02). The median duration of first CR was 18.2 mo for patients whose cells showed a low expression of GST pi compared with 6.7 mo for those that entered CR in spite of a high expression of the enzyme (P less than or equal to 0.005). Of cells from ten patients that at the time of study were in a continuous first CR, none expressed high concentrations of GST pi. The expression of GST pi remained rather constant in most patients as the disease progressed to clinical resistance. At relapse there was no significant correlation between the expression of GST pi and treatment results but, of ten patients that entered a second CR or achieved a partial remission, only one showed a high expression of the enzyme. We conclude that there was a significant correlation between the expression of GST pi at the time of diagnosis and the subsequent treatment results and that GST pi is a useful marker for clinical resistance to cytostatic drugs in acute nonlymphoblastic leukemia. PMID- 1596887 TI - Overexpression of cholecystokinin receptors in azaserine-induced neoplasms of the rat pancreas. AB - Cholecystokinin (CCK) is a growth factor for normal pancreas. Numerous studies also suggest that CCK promotes pancreatic carcinogenesis in the rat. Our previous studies suggested that growth of preneoplastic pancreatic foci was stimulated by CCK more than that of normal pancreas. We hypothesized that such differential growth might be due to increased numbers of CCK receptors in neoplastic tissue. Azaserine-induced pancreatic carcinoma (DSL6) had an increased high-affinity CCK receptor binding capacity of 122 +/- 23 (SD) fmol/mg protein compared to 12 +/- 2 fmol/mg protein in normal pancreas (P less than 0.001). The Kd of the high affinity site was 0.33 +/- 0.04 nM for carcinoma and 0.46 +/- 0.08 nM for normal pancreas (P less than 0.01). The amount of cholecystokinin octapeptide (CCK-8) bound to high-affinity receptor was 8.6 +/- 1.9 fmol/mg protein for DSL6 compared to 0.6 +/- 0.2 fmol/mg protein in normal pancreas (P less than 0.001). Azaserine induced premalignant nodules were compared to remaining internodular pancreas. Nodules demonstrated a mean high-affinity CCK receptor binding capacity of 38 +/- 9 fmol/mg protein compared to 6 +/- 3 fmol/mg protein in internodular pancreas (P less than 0.001). The amount of CCK-8 bound to high-affinity receptor was 3.1 +/- 0.8 fmol/mg protein in nodules compared to 0.6 +/- 0.3 fmol/mg protein in internodular pancreas (P less than 0.001). Overexpression of high-affinity CCK-8 receptor in premalignant and malignant azaserine-induced tumors may result in a growth advantage relative to normal pancreas. PMID- 1596888 TI - Activation of a beta-hydroxyalkylnitrosamine to alkylating agents: evidence for the involvement of a sulfotransferase. AB - N-Nitrosomethyl(2-hydroxyethyl)amine (NMHEA), when administered by gavage, is a strong liver carcinogen in F344 female rats, but a weak liver carcinogen in male rats. After repeated exposure to NMHEA, either in drinking water or by gavage, female rats accumulated higher levels of DNA-guanine adducts than did their male counterparts, suggesting a correlation with the observed disparity in carcinogenicity. NMHEA has been shown to alkylate rat liver DNA in vivo in a dose dependent manner. Chemical investigations of NMHEA suggest that it becomes a strong electrophile when a good leaving group is substituted on the hydroxyl. We have proposed that NMHEA is activated to its ultimate carcinogenic form by conjugation with sulfate. The sulfate ester was postulated to undergo rapid cyclization to 3-methyl-1,2,3-oxadizolinium ion, which has previously been found to be a potent methylating agent in vitro. The effect of sulfotransferase inhibitors on the DNA alkylation in rats by NMHEA was studied in vivo. Dichloronitrophenol, a powerful inhibitor of phenol sulfotransferase, had little effect on the methylation and O6-hydroxyethylation of DNA guanine in female rats, while depressing the hydroxyethylation of the N-7 position of guanine. Dichloronitrophenol, however, dramatically enhanced the methylation of DNA in male rats. It also slightly inhibited the N-nitrosodimethylamine-induced methylation of DNA. On the other hand, propylene glycol, an alcohol sulfotransferase inhibitor, had a profound inhibitory effect on DNA methylation induced by NMHEA, very little effect on the formation of N7-(2 hydroxyethyl)guanine, but a very strong effect on the O6-hydroxyethylguanine lesions. NMHEA-induced alkylation was also studied in male and female brachymorphic mice, which are deficient in the ability to synthesize the sulfate donor 3'-phosphoadenosine 5'-phosphosulfate required for sulfotransferase activity, and their heterozygous siblings. No significant differences were seen between the heterozygous and brachymorphic mice in overall levels of alkylation, except in the case of 7-hydroxyethylation. In contrast to rats, male mice showed higher levels of formation of all DNA guanine adducts than did the females. However, propylene glycol was found to depress all the levels of alkylation in the brachymorphic mice, except for N7-(2-hydroxyethyl)guanine, as was observed in rats.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1596889 TI - Flavone acetic acid increases the antitumor effect of hyperthermia in mice. AB - The combined effects of flavone acetic acid (FAA), a synthetic flavonoid, and hyperthermia on B16 melanoma cells were investigated. In vitro, FAA alone at concentrations below 100 micrograms/ml was not cytotoxic with a 60-min exposure at 37 degrees C. Hyperthermia at 43 degrees C for 60 min enhanced the cytotoxicity of FAA only at concentrations over 100 micrograms/ml. Inhibition of the growth of B16 melanoma solid tumor by FAA and/or hyperthermia was examined in vivo. FAA (100-200 mg/kg) inhibited tumor growth in a dose-dependent manner. The combined treatment of FAA (200 mg/kg) and hyperthermia (43 degrees C, 15 min) significantly inhibited tumor growth compared to a treatment of FAA or hyperthermia alone. The maximum antitumor effect of FAA combined with hperthermia was obtained when FAA was administered 2 or 4 h before heat. The significantly increased cytotoxicity of FAA combined with hyperthermia seems to relate to specific decreases in tumor blood flow, a reduction in tumor pH, and an increased tumor temperature, without altering pH in the normal tissues. This combined treatment of FAA and hyperthermia warrants further study for treating subjects with solid tumors. PMID- 1596890 TI - Serum level of interleukin 6 as a prognosis factor in metastatic renal cell carcinoma. AB - Interleukin (IL) 6 was measured in the serum of 138 patients with metastatic renal carcinoma before the initiation of IL-2 treatment. IL-6 was detectable in 66 patients with renal cancer (48%) and in only 8 of 70 normal adults (11%). Serum C reactive protein (CRP) and IL-6 levels are correlated, suggesting that IL 6 is involved in CRP increase in these patients. The interval between diagnosis of the primary tumor and metastasis was shorter in patients with a detectable serum IL-6 and/or serum CRP level greater than 50 mg/liter. Serum IL-6 and CRP levels were higher in subgroups of patients previously defined as having a poor life expectancy according to the Eastern Cooperative Oncology Group criteria. Pretreatment concentrations of IL-6 and CRP were higher in patients who experienced progressive disease after IL-2 treatment. Patients with detectable IL 6 had a shorter survival from the beginning of IL-2 treatment than patients without circulating IL-6 (median, 8 versus 16 months). Similarly, the median survival from the beginning of IL-2 therapy of patients with CRP levels greater than 50 mg/liter was 6 months, compared to 16 months in those with CRP levels below this threshold. None of the 21 patients with serum IL-6 concentrations greater than 300 pg/ml achieved response to any of the three IL-2 regimens. This subgroup has a median survival of 5 months after IL-2 treatment and consisted of 15% of the patients in our series. These results indicate that serum IL-6 and CRP levels are adverse prognosis factors in patients with metastatic renal cell carcinoma. Serum IL-6 level could help in the selection or stratification of the patients in future IL-2 trials. PMID- 1596891 TI - Growth regulation of human renal carcinoma cells: role of transforming growth factor alpha. AB - Findings of increased numbers of epidermal growth factor receptors (EGF-R) and increased expression of transforming growth factor alpha (TGF-alpha) in surgical specimens of human renal cell carcinoma have led to the proposal that growth of these tumors may be regulated by TGF-alpha in an autocrine manner. In the studies presented here, we have examined this hypothesis using two human renal carcinoma cell lines, SKRC-4 and SKRC-29. We demonstrated that both SKRC-4 and SKRC-29 cells were growth stimulated by greater than 35% when cultured in the presence of TGF-alpha or EGF and were inhibited by 29% to 46% if cultured in the presence of anti-EGF-R monoclonal antibody 225. Treatment of cells with TGF-alpha enhanced the levels of expression of EGF-R mRNA and TGF-alpha mRNA. In addition, incubation of cells with monoclonal antibody 225 significantly elevated the levels of excreted TGF-alpha species in the culture medium. Our findings suggest that proliferation of human renal carcinoma cells may be regulated by endogenously produced TGF-alpha and that this regulatory pathway can be interrupted using antibody to its receptor, EGF-R. PMID- 1596892 TI - Activation of the Ha-, Ki-, and N-ras genes in chemically induced liver tumors from CD-1 mice. AB - We compared the profile of ras gene mutations in spontaneous CD-1 mouse liver tumors with that found in liver tumors that were induced by a single i.p. injection of either 7,12-dimethylbenz(a)anthracene (DMBA), 4-aminoazobenzene, N hydroxy-2-acetylaminofluorene, or N-nitrosodiethylamine. By direct sequencing of polymerase chain reaction-amplified tumor DNA, the carcinogen-induced tumors were found to have much higher frequencies of ras gene activation than spontaneous tumors. Furthermore, each carcinogen caused specific types of ras mutations not detected in spontaneous tumors, including several novel mutations not previously associated with either the carcinogen or mouse hepatocarcinogenesis. For example, the model compound DMBA is known to cause predominantly A to T transversions in Ha-ras codon 61 in mouse skin and mammary tumors, consistent with the ability of DMBA to form bulky adducts with adenosine. Our results demonstrate that the predominant mutation caused by DMBA in mouse liver tumors is a G to C transversion in Ki-ras codon 13 (DMBA is also known to form guanosine adducts), illustrating the influence of both chemical- and tissue-specific factors in determining the type of ras gene mutations in a tumor. 4-Aminoazobenzene and N hydroxy-2-acetylaminofluorene also caused the Ki-ras codon 13 mutation. In addition, we found that N-nitrosodiethylamine, 4-aminoazobenzene, and N-hydroxy-2 acetylaminofluorene all caused G to T transversions in the N-ras gene (codons 12 or 13). This is the first demonstration of N-ras mutations in mouse liver tumors, establishing a role for the N-ras gene in mouse liver carcinogenesis. Finally, comparison of the ras mutations detected in the direct tumor analysis with those detected after NIH3T3 cell transfection indicates that spontaneous ras mutations (in Ha-ras codon 61) are often present in only a small fraction of the tumor cells, raising the possibility that they may sometimes occur as a late event in CD-1 mouse hepatocarcinogenesis. PMID- 1596893 TI - Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. AB - In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene. PMID- 1596894 TI - Induction of interleukin 2 production but not methionine adenosyltransferase activity or S-adenosylmethionine turnover in Jurkat T-cells. AB - We have recently reported that methionine adenosyltransferase (MAT) in resting human peripheral blood T-cells is primarily present in the form of a precursor which we named lambda. This protein decreases upon cell stimulation, as both MAT activity and the amount of the catalytic alpha/alpha' subunits of the enzyme increase. When resting cells are activated by phytohemagglutinin, the decrease in lambda and increase in alpha/alpha' occurs after interleukin 2 (IL-2) production and before DNA synthesis. The human T-leukemia cell line, Jurkat, is unique in its ability to produce IL-2 in response to exogenous stimuli such as T-cell mitogens and therefore provides a convenient model for studying biochemical reactions involved in T-cell activation. In this study the regulation of MAT activity and S-adenosylmethionine (AdoMet) in resting and activated Jurkat cells was investigated. Here we report that MAT activity in unstimulated Jurkat cells is about 10- and 3-fold higher than the activity in resting and activated peripheral blood mononuclear cells, respectively. Activation of Jurkat cells with phytohemagglutinin resulted in increased IL-2-production, but not an increase in MAT activity. Identical results were obtained using freshly isolated cells from acute lymphoblastic leukemia patients. AdoMet utilization and pool size were approximately 3- and 10-fold higher, respectively, in Jurkat cells compared to peripheral blood mononuclear cells, and both parameters were unaffected by phytohemagglutinin stimulation. Jurkat MAT was determined to be structurally indistinguishable from enzyme from T- or B-leukemia cells but was different from resting, normal T-cells in that it lacked the lambda form. Furthermore, unlike MAT in resting T-cells, the relative amounts of the alpha, alpha', and beta subunits of the enzyme did not change throughout the course of IL-2 induction. We conclude that AdoMet metabolism and MAT activity in Jurkat cells are constitutively high and that induction of IL-2 synthesis in these cells is independent of changes in AdoMet synthesis or turnover. The lack of the lambda form and the difference in MAT regulation between leukemic T-cells and peripheral blood mononuclear cells may be exploited in the design of specific chemotherapeutic agents. PMID- 1596895 TI - Genes preferentially expressed in embryo stomach are predominantly expressed in gastric cancer. AB - Eight complementary DNA (cDNA) clones highly expressed in fetal rat stomach but not in normal adult rat stomach were isolated after screening 2 x 10(4) independent recombinants from a subtracted cDNA library. The cDNA library was first prepared from RNAs of total stomach at 16 days gestational period, and this cDNA library was subtracted by cDNAs prepared from adult rat total stomach RNA, using a novel PCR-based cDNA subtraction method. Northern blot analysis revealed that as many as six of eight clones thus isolated were overexpressed in at least some of the human or rat gastric cancers. From analysis of partial nucleotide sequence, four cDNA clones were identified as profilin, pro-alpha 1 (1) collagen, nucleolar protein B23.2, and elongation factor 1 alpha subunit. The remaining two clones were derived from novel genes. These novel genes, L-1 and L-2, are developmentally well regulated in the stomach. The present results clearly show that genes expressed preferentially in embryo stomach are most likely to be highly expressed in gastric cancer. The method described here provides us with a rapid method for identification of genes with significantly increased expression in cancer. PMID- 1596896 TI - Transcriptional regulation of the human placental-like alkaline phosphatase gene and mechanisms involved in its induction by sodium butyrate. AB - The human alkaline phosphatases constitute a multigene family with at least four members. Placental-like alkaline phosphatase (PLAP) is of particular interest because it is frequently present in tumors, where it serves as a marker of malignant transformation. Moreover, its expression is highly inducible by differentiating agents such as sodium butyrate. In the present study we have examined the PLAP gene promoter in order to better understand the mechanisms involved in its expression and induction. The PLAP promoters from four colon cancer cell lines with widely varied butyrate-inducible alkaline phosphatase activity were thermally amplified and sequenced. The overall sequence similarity of this region was found to be 99% between cell lines; thus, sequence variation of the promoter does not appear to account for the differential expression of this marker. We therefore analyzed the activity of the LS174T cell PLAP promoter using transient transfection experiments. Here, the 5'-flanking region of the gene was found to have positive regulatory elements in nucleotides -1 to -170 and -363 to -512 (relative to the start of transcription). A negative control element was also found to be present in the region between nucleotides -170 and -363. Mobility shift electrophoresis indicated that a nuclear factor bound to the promoter between bases -182 and -341. Furthermore, the activity of the PLAP promoter was found to be inducible by sodium butyrate. In contrast, the closely related placental alkaline phosphatase gene promoter exhibited almost no response to this agent. These results confirm that the activity of the PLAP promoter is stimulated by sodium butyrate and delineate regions that control this induction process. PMID- 1596897 TI - Teniposide induces nuclear but not mitochondrial DNA degradation. AB - Teniposide [4'-demethylepipophyllotoxin-4-(4,6-O-thenylidene-beta-D- glucopyranoside) (VM-26)] is a cancer chemotherapeutic drug with a high target specificity for DNA topoisomerase II. This agent induces repairable protein bridged double-strand DNA breaks, which have been correlated with cytotoxicity, but high concentrations of VM-26 also induce irreversible DNA degradation and apoptotic cell death. It is not known whether this degradation occurs uniformly throughout the genome or in a gene-specific manner. To answer this question, DNA was isolated from HL-60 promyelocytic leukemia cells exposed to 5 microM VM-26 for varying periods of up to 12 h. Nucleosomal "ladders" on 2.0% agarose gels stained with ethidium bromide were detectable after 3 h of exposure, indicative of apoptosis. Gene-specific DNA degradation was investigated by Southern blot analysis. The genes for 18S rRNA and glucose-6-phosphate dehydrogenase were representatives of constitutively expressed (i.e., "housekeeping") genes. The proto-oncogenes c-myc, c-Ha-ras, and bcl-2 were examined as examples of other transcriptionally active genes, while transcriptionally inactive genes in HL-60 cells were studied by probing for the immunoglobulin heavy chain joining region and lambda light chain constant region genes. The rates of DNA degradation, and its extent after 12 h, were similar for all nuclear genes studied. However, there was striking resistance of mitochondrial DNA to endonucleolytic degradation. These data demonstrate that VM-26 can elicit a widespread degradative process which affects nuclear but not mitochondrial DNA. PMID- 1596898 TI - Evidence for a 17p tumor related locus distinct from p53 in pediatric primitive neuroectodermal tumors. AB - Primitive neuroectodermal tumors of the central nervous system are the most common malignant brain tumors in children. Cytogenetic analysis of these tumors has demonstrated alterations of chromosome 17, in particular isochromosome 17q, as the most frequent chromosomal abnormality detected. Since the consistent loss of a specific chromosomal region in a given tumor type most likely indicates the presence of a tumor related gene in that region, we undertook a combined molecular and cytogenetic approach to examine alterations of chromosome 17 in primitive neuroectodermal tumors. Seven of 14 tumors analyzed demonstrated loss of alleles for loci on 17p. In three of the seven tumors tested, a loss in copy number was observed for only the most telomeric locus on 17p13.3, D17S34. Limited sequence analysis of the same seven tumors did not reveal mutations in four highly conserved coding regions of the p53 gene. These data suggest a new tumor associated locus on 17p distinct from and distal to TP53, which is involved in the initiation or progression of at least a subset of primitive neuroectodermal tumors. PMID- 1596899 TI - Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. AB - In some epithelial cells studied in vitro a membrane-bound folate receptor initiates the process for cell accumulation of 5-methyltetrahydrofolic acid. This receptor was found to be GP38, an overexpressed, glycosyl-phosphatidylinositol anchored glycoprotein, recognized by two monoclonal antibodies, designated MOv18 and MOv19. Using immunoblotting with MOv19, radioimmunoassay with MOv18 and 19, Northern blot analysis, and radioligand binding when possible, we describe the limited expression of the folate receptor in a large number of normal tissues from four autopsies. The immunoblot technique detected as little as 40 pg (approximately 1 fmol) of receptor protein. Choroid plexus consistently had the largest amount of folate receptor. Other tissues containing substantial amounts of receptor included lung, thyroid, and kidney. The liver, intestines, muscle, cerebellum, cerebrum, and spinal cord were immunologically nonreactive. Folate receptor gene expression determined by Northern blot analysis confirmed these observations. We also show that several malignant cell lines express significantly more receptor than normal epithelial cells or fibroblasts. Specifically, malignant cells bound greater than or equal to 20 pmol [3H]folate/10(6) cells, while normal epithelial cells and fibroblasts bound less than or equal to 1 pmol radioligand/10(6) cells. We also demonstrate that 4 of 6 brain tumors overexpress the folate receptor. These studies reveal the limited normal tissue distribution of the folate receptor, a cell surface protein which may be a useful immunological or pharmacological target for the development of selective cancer therapy. PMID- 1596901 TI - Interleukin 2 acutely induces platelet and neutrophil-endothelial adherence and macromolecular leakage. AB - The acute effects of interleukin 2 (IL-2) were determined in the rat cremaster microcirculation model by intravital, light, and electron microscopy to better understand the pathophysiology of the IL-2-induced vascular leak syndrome. Four groups of rats were studied over a 2-h monitoring period. One group received 1 x 10(6) units of IL-2/kg i.v. (n = 10), while the remaining groups received IL-2 topically applied to the cremaster muscle in dosages of either 1 x 10(5) (n = 9), 1 x 10(6) (n = 5), or 3 x 10(6) (n = 5) units. Each group was compared with controls (n = 9). IL-2 administered i.v. acutely induced platelet and polymorphonuclear leukocyte-endothelial adherence and microvascular macromolecular leakage that occurred synchronous with the development of tachycardia, hypotension, tachypnea, and hypoxemia. Topically applied IL-2 induced similar microvascular alterations but without changes in hemodynamic and respiratory parameters, which suggests that microvascular alterations were not caused by IL-2-induced changes in hemodynamic parameters. Electron microscopy of cremaster muscle sections demonstrated platelet and neutrophil adherence to the endothelium and endothelial injury. We conclude that IL-2 (or a locally generated mediator) acutely induces platelet and neutrophil-endothelial adherence in the rat skeletal muscle microcirculation that is associated with the development of macromolecular leakage from the microcirculation. PMID- 1596900 TI - Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. AB - Single-chain antigen-binding proteins, or sFvs, represent potentially unique molecules for targeted delivery of drugs, toxins, or radionuclides to a tumor site. In previous studies (Cancer Res., 51:6363-6371, 1991) using a human colon carcinoma xenograft model, it was demonstrated that the sFv has an extremely rapid plasma and whole body clearance, as compared to intact IgG or Ig fragments. One potential consequence of the rapid sFv pharmacokinetic properties was the reduced percentage of injected dose/g of the radiolabeled sFv found in the tumor throughout a range of time points. The present study was designed to define the tumor penetration properties of a radiolabeled sFv in comparison with other Ig forms. 125I-labeled sFv, Fab', F(ab')2, and IgG forms of monoclonal antibody CC49, directed against the human pancarcinoma antigen TAG-72, were used to target the LS-174T human colon carcinoma xenograft in athymic mice. At various time points after systemic Ig administration, quantitative autoradiographic analyses of surgically removed tumors were used to define the rate and degree of penetration of the various Ig forms. These studies revealed that most of the intact IgG delivered to the tumor was concentrated in the region of or immediately adjacent to vessels, while the sFv was more evenly distributed throughout the tumor mass. The distributions of the Fab' and F(ab')2 fragments showed intermediate penetration in a size-related manner. The sFv demonstrated maximum tumor penetration at 0.5 h postinjection, while the intact IgG reached an equivalent degree of penetration at 48 to 96 h postinjection. These studies thus reveal a greater degree of uptake throughout the tumor for the sFv than would be expected by gross analyses of percentage injected dose/g and demonstrate an extremely rapid tumor penetration of the sFv. These studies should aid in the rational design of potential applications of drug-, toxin-, and radionuclide conjugated sFvs in cancer therapy. PMID- 1596902 TI - Dose-response relationships for chronic exposure to 2,3,7,8-tetrachlorodibenzo-p dioxin in a rat tumor promotion model: quantification and immunolocalization of CYP1A1 and CYP1A2 in the liver. AB - The mechanisms responsible for the braod spectrum of effects of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) are not entirely clear but seem to involve an initial interaction with the Ah receptor. A major uncertainty in risk assessment for TCDD is the lack of adequate dose-response relationships following chronic exposure to TCDD. Induction of cytochrome P-450 enzymes (CYP1A1 and CYP1A2) is one of the most sensitive responses to TCDD and its structural analogues. We have used a two-stage model for hepatocarcinogenesis in female Sprague-Dawley rats to evaluate dose-response relationships for induction of CYP1A1 and CYP1A2 in diethylnitrosamine-initiated as well as in noninitiated rats. After initiation with a single dose of diethylnitrosamine, TCDD was administered biweekly by p.o. gavage at doses equivalent to 3.5, 10.7, 35.7, and 125 ng/kg/day for 30 weeks. CYP1A1 and CYP1A2 concentrations were quantified in hepatic microsomes by radioimmunoassay and localized in hepatic tissue slices by immunohistochemical techniques. Radioimmunoassay data revealed a maximum induction of 200-fold for CYP1A1 and 10-fold for CYP1A2 and there were no statistically significant differences between initiated and noninitiated rats. Induction at the lowest dose (3.5 ng/kg/day) was 20-fold for CYP1A1 and 3-fold for CYP1A2. Mathematical analysis indicates that the best fit of the induction data are inconsistent with a threshold for this response. There was a linear relationship between administered dose and TCDD liver concentration over the entire dose range of the study. This indicates that induction of CYP1A2 does not significantly alter the distribution of TCDD in our chronic dosing regimen. Immunolocalization of CYP1A1 and CYP1A2 revealed the same localization and induction pattern for both isozymes in the cytoplasm of hepatocytes. However, the hepatic distribution pattern was not uniform with the most intense staining observed around central veins. These studies help to clarify dose-response relationships for dioxin-mediated effects and demonstrate different sensitivity of hepatocytes to the effects of TCDD. PMID- 1596903 TI - Expression of class II major histocompatibility complex molecules correlates with human colon tumor vaccine efficacy. AB - Vaccination of colon cancer patients with X-irradiated autologous tumor cells and Bacillus Calmette-Guerin results in a significant reduction in tumor recurrence. A study was undertaken to determine whether the expression of tumor-associated antigens, expression of major histocompatibility complex molecules, or the cellular composition of the vaccine cells correlates with vaccine efficacy. A significant increase in the percentage of histocompatibility leukocyte antigen (HLA) class II molecule-expressing tumor cells was the only marker with a positive correlation. Because HLA class II molecule expression is not a prognostic marker in control patients, it was hypothesized that HLA class II molecules are involved in the induction of tumor immunity in patients treated with the autologous colon tumor vaccine. Enhancement of HLA class II molecule expressing cells could be induced in X-irradiated colon tumor cells injected into the skin of mice when the cells were mixed with gamma-interferon. Therefore, addition of gamma-interferon to the colon tumor vaccine, resulting in increased numbers of HLA class II molecule-expressing cells, could potentiate the generation of tumor immunity. PMID- 1596905 TI - Neoplastic transformation of immortalized human keratinocytes by 2,3,7,8 tetrachlorodibenzo-p-dioxin. AB - 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most powerful carcinogen ever tested in animals. Recent epidemiological studies have suggested its carcinogenic potential in humans. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus 12-simian virus 40 (Ad12-SV40) were transformed by exposures of TCDD equal to or greater than 0.1 nM for 2 wk. These transformed cells showed morphological alterations and induced carcinomas when transplanted into nude mice, whereas no such transformation phenotypes were observed with exposures of less than 0.1 nM for 2 wk. Primary human epithelial keratinocytes exposed to various concentrations of TCDD failed to show any evidence of transformation. Induction of aryl hydrocarbon hydroxylase activity was dose dependent, as was transformation. Thus, the carcinogenicity of TCDD in this human cell system appears to be an Ah receptor-mediated process. The present study represents the first evidence of neoplastic conversion of human cells exposed to this environmentally important chemical. PMID- 1596904 TI - Differential immunohistochemical detection of amphiregulin and cripto in human normal colon and colorectal tumors. AB - Thirty-six primary human colorectal tumors, 43 noninvolved colon samples that were adjacent to either carcinomas of adenomas, 22 adenomas, and nine normal colon specimens were immunohistochemically examined for the presence and localization of two epidermal growth factor-related peptides, amphiregulin (AR) and cripto. Within the primary tumors, 18 (50%) showed moderate levels of AR expression. Approximately 60% of the tubular and tubulovillous adenomas were positive for AR expression, whereas only 15% of the adjacent, noninvolved colon mucosa expressed AR. A greater proportion of well-differentiated tumors (71%) were positive for AR expression than were poorly differentiated tumors (18%). All of the nine normal colon specimens were positive. Consequently, AR expression appeared to be associated with both normal and malignant epithelial cells that were more differentiated. The distribution of cripto expression was different. Seventy-nine % of the colon tumors expressed cripto with a frequency of expression that was approximately equivalent between well-differentiated and poorly differentiated tumors. Approximately 86% of the tubulovillous adenomas, but only 43% of the tubular adenomas, were positive for cripto expression. In contrast, whereas AR was expressed in normal colon specimens, none of these tissues expressed cripto, and only 12% of the noninvolved normal colon samples adjacent to tumors or adenomas were positive for cripto. Cripto expression therefore appeared related to neoplasia. These data suggest that AR and cripto may be functioning as potential autocrine and/or paracrine growth factors in the colon and that the differential expression of cripto may serve as a potential tumor marker for colonic carcinogenesis. PMID- 1596906 TI - c-Ha-ras containing 8-hydroxyguanine at codon 12 induces point mutations at the modified and adjacent positions. AB - To determine the type of mutation induced by 8-hydroxyguanine in a mammalian system, we examined the mutations induced by a synthetic c-Ha-ras protooncogene containing 8-hydroxyguanine in the second position of codon 12 (GGC) in NIH3T3 cells. Transfection of this gene significantly increased the number of transformed foci. The c-Ha-ras gene present in these foci was analyzed by the polymerase chain reaction-restriction enzyme method. Interestingly, sequence analysis revealed random mutations at the modified site (G----T, G----A, and G--- C) as well as mutations of the adjacent G on the 5'-side of 8-hydroxyguanine (G-- -A and G----T). PMID- 1596907 TI - Localization of metastasis suppressor gene(s) for prostatic cancer to the short arm of human chromosome 11. AB - Previous studies using somatic cell hybridization of highly metastatic and nonmetastatic rat prostatic cancer cells demonstrated that the resultant hybrids were nonmetastatic if all of the parental chromosomes were retained. Somatic hybrid segregants which underwent nonrandom chromosomal losses reexpressed high metastatic ability. These results demonstrated that there are gene(s) the expression of which can suppress metastatic ability of prostatic cancer cells. To identify the location of homologous gene(s) in the human, specific human chromosomes were introduced into highly metastatic rat prostatic cancer cells using the microcell-mediated chromosome transfer. Introduction of human chromosome 11 into highly metastatic rat prostate cancer cells results in suppression of metastatic ability without suppression of the in vivo growth rate or tumorigenicity of the hybrid cells. Spontaneous deletion of portions of human chromosome 11 in some of the clones delineated the minimal portion of human chromosome 11 capable of suppressing prostatic cancer metastases as the region between 11p11.2-13 but not including the Wilms' tumor-1 locus. PMID- 1596908 TI - Cell cycle-related expression of p120 nucleolar antigen in normal human lymphocytes and in cells of HL-60 and MOLT-4 leukemic lines: effects of methotrexate, camptothecin, and teniposide. AB - Expression of the proliferation-associated nucleolar antigen p120 was studied by flow cytometry in human quiescent and phytohemagglutinin-stimulated lymphocytes, as well as in human lymphocytic (MOLT-4) and promyelocytic (HL-60) cell lines. Bivariate analysis of p120 and DNA content made it possible to correlate p120 expression with cell position in the cycle. Proliferating lymphocytes and MOLT-4 and HL-60 cells had a similar pattern of p120 expression. Populations of G1 cells, in all three cell types, were very heterogenous with respect to p120, and a threshold in G1 was observed. The cells with a p120 level below the threshold value did not enter S phase. An increase in p120 was observed during progression through S phase, and the antigen was maximally expressed in G2 cells. The p120/DNA content ratio, however, was highest in late G1 cells (G1B) and was declining during S and G2. The data thus suggest that p120 may be degraded during mitosis and that the postmitotic cells inherit little, if any, of this protein; the antigen then accumulates predominantly during G1, and must reach a threshold level to enable the cells to enter S phase. Antigen p120 could not be detected in noncycling lymphocytes nor in HL-60 cells induced to myeloid differentiation by growth in the presence of dimethyl sulfoxide. Treatment of MOLT-4 cells with pharmacological concentrations of methotrexate, camptothecin, or teniposide induced cell arrest in S or G2; expression of p120 in the arrested cells was unchanged from that of untreated MOLT-4 controls at the same phase of the cycle. The level of p120 was minimal in MOLT-4 or HL-60 cells arrested in M phase by vinblastine, but vinblastine had no effect on p120 fluorescence of interphase cells. Camptothecin or teniposide induced apoptosis selectively in S phase of HL 60 cells; apoptotic cells from camptothecin-treated cultures, however, despite the marked nucleolysis, still expressed p120. The data on the drug-treated cells indicate that the p120 level in tumors of patients may be used as a marker of tumor/malignancy even in clinical samples obtained during treatment. PMID- 1596909 TI - Modulation of the cytotoxic effect of cyclopentenylcytosine by its primary metabolite, cyclopentenyluridine. AB - Cyclopentenylcytosine (CPE-C), a synthetic cytidine analogue with significant preclinical antitumor activity against both solid tumor xenografts and 1-beta-D arabinofuranosylcytosine resistant murine leukemia cell lines, will soon enter phase I clinical trials. Unlike 1-beta-D-arabinofuranosylcytosine which is activated by deoxycytidine kinase, the enzyme responsible for the phosphorylation of CPE-C is uridine/cytidine kinase. Preclinical pharmacokinetic studies of CPE-C in nonhuman primates revealed that the primary route of elimination in this species was deamination to cyclopentenyluridine (CPE-U), an inhibitor of uridine/cytidine kinase. Since CPE-C is likely to be deaminated in humans, we investigated the modulating effect of CPE-U on the in vitro cytotoxicity of CPE-C in Molt-4 lymphoblasts. Concurrent exposure of cells to cytotoxic concentrations of CPE-C and 50 microM CPE-U resulted in the rescue of 50% of cells and exposure to CPE-U concentrations in excess of 100 microM resulted in the rescue of greater than 90% of cells. Progressive attenuation of the rescue effect was observed with delayed administration of CPE-U and no cells were rescued when addition of CPE-C was delayed for more than 2 h. At the intracellular level it was observed that the formation of the cytotoxic metabolite, cyclopentenylcytosine triphosphate, was blocked by increasing concentrations of CPE-U presumably secondary to inhibition of uridine/cytidine kinase by CPE-U. Although CPE-U can modulate the cytotoxic effects of CPE-C in vitro, the minimum CPE-U levels that are required for modulation coupled with the available preclinical pharmacokinetic data from nonhuman primates suggests that this modulation is not likely to impact on the antitumor effects of CPE-C in humans. PMID- 1596910 TI - Molecular analysis of the protein tyrosine phosphatase gamma gene in human lung cancer cell lines. AB - The protein tyrosine phosphatase gamma (PTP gamma) gene has recently been suggested as a candidate tumor suppressor gene involved in the oncogenesis of human lung and renal cancers, although no direct evidence for PTP gamma mutations has been demonstrated thus far. We explored the status of PTP gamma in 31 human lung cancer cell lines as well as in various other types of human tumor cell lines. Northern blot analysis revealed that two independent cell lines expressed PTP gamma mRNAs with sizes distinct from those in human fetal and adult normal lung. However, our extensive search for mutations in the PTP gamma gene failed to identify any abnormalities in the cytoplasmic region, which contains two protein tyrosine phosphatase-like domains. These results warrant further examination of genetic alterations in the extracellular and transmembrane domains of PTP gamma, which had not been cloned at the time of the present study. PMID- 1596911 TI - Preparation of di-O-triphenylmethyl-(trityl-) cyclomaltohexaoses and cyclomaltoheptaoses and characterization of three positional isomers of each by the "hex-5-enose degradation". AB - Regioisomeric 6(1),6n-di-O-trityl-cyclomaltohexaoses (cG6s) or cyclomaltoheptaoses (cG7s) were prepared by the reaction of cyclomaltohexaose (1, cG6) or cylomaltoheptaose (5, cG7) with chlorotriphenyl-methane in pyridine and isolation by h.p.l.c. The regiochemical determination of each three ditrityl substituted derivatives has been accomplished by the "hex-5-enose degradation", followed by measurement of their f.a.b.-mass spectra. PMID- 1596912 TI - Synthesis of di-O-glycosyl derivatives of methyl alpha-L-rhamnopyranoside. AB - The syntheses are described of 2,3-di-O-glycosyl derivatives (1-12) of methyl alpha-L-rhamnopyranoside where the glycosyl moieties are variously alpha-L fucopyranose, beta-L-fucopyranose, beta-D-glucopyranose, alpha-D-mannopyranose, and alpha-L-rhamnopyranose. The syntheses involve stereoselective glycosylation of methyl 4-O-benzoyl-3-O-(2,3,4-tri-O-benzoyl-alpha-L- rhamnopyranosyl)-alpha-L rhamnopyranoside (21), methyl 4-O-benzoyl-3-O-(2,3,4,6-tetra-O-benzoyl-alpha-D mannopyranosyl)- alpha-L-rhamnopyranoside (25), methyl 4-O-benzoyl-3-O-(2,3,4,6 tetra-O-benzoyl-beta-D-glucopyranosyl)- alpha-L-rhamnopyranoside (29), methyl 4-O benzoyl-3-O-(2,3,4-tri-O-benzoyl-beta-L-fucopyranosyl)-alpha-L- rhamnopyranoside (35), and methyl 4-O-benzyl-2-O-(2,3,4-tri-O-benzoyl-beta-L-fucopyranosyl)- alpha L-rhamnopyranoside (59). In the syntheses of compounds 7-9, the alpha-L fucopyranosyl residues are introduced stereoselectively, using 2,3,4-tri-O benzoyl-alpha-L-fucopyranosyl bromide (17) and ethyl 2,3,4-tri-O-acetyl-1-thio beta-L-fucopyranoside (47) as glycosyl donors. PMID- 1596913 TI - The crystal structure of D-threitol at 119 K and 198 K. AB - A sample of DL-threitol, C4H10O4 (Sigma Chemical Co.), on recrystallization provided crystals of D- and L-threitol. The crystal structure was determined at 119 K and 298 K. The space group of D-threitol is P3(1)21, with three molecules in a unit cell at 119 K [298 K] of a = 10.0995(5) [10.1405(8)], c = 4.8407(4) [4.8767(4)] A. The final agreement R-factor was 0.050 for 302 intensities [0.069 for 244 intensities]. The molecules have the straight carbon-chain conformation with twofold axial symmetry. The hydroxyl groups are hydrogen bonded in infinite chains extending in the direction of the threefold screw axis. One of the hydroxyl hydrogens is twofold disordered, so that alternate chains have reversed donor-acceptor directions. PMID- 1596914 TI - Photolabile derivatives of maltose and maltotriose as ligands for the affinity labelling of the maltodextrin-binding site in porcine pancreatic alpha-amylase. AB - The 3-azibutyl group was linked through sulfur to the anomeric position of maltose and maltotriose to yield the photolabile thioglycosides 3-azibutyl 1-thio alpha-maltoside (11) and 3-azibutyl 1-thio-alpha-maltotrioside (12), and to the 4'- and 6'-position of maltose to give the thioethers 4'-S-(3-azibutyl)-4' thiomaltose (8) and 6'-S-(3-azibutyl)-6'-thiomaltose (15). All four compounds were good competitive inhibitors of the action of porcine pancreatic alpha amylase. Compound 12 irreversibly deactivated the enzyme to approximately 100% when irradiated together with the protein. The other compounds were much less effective. It is likely that separate areas of the enzyme binding site are chemically modified by the different ligands. PMID- 1596915 TI - Efficient and stereoselective synthesis of methyl 3-O-(3,6-anhydro-beta-D galactopyranosyl)-alpha-D-galactopyranoside and methyl 3,6-anhydro-4-O-beta-D galactopyranosyl-alpha-D-galactopyranoside. AB - Methyl 3-O-(3,6-anhydro-beta-D-galactopyranosyl)-alpha-D-galactopyranoside (3) and methyl 3,6-anhydro-4-O-beta-D-galactopyranosyl-alpha-D-galactopyranoside (4) have been synthesised stereoselectively using three coupling procedures. Acceptable yields were achieved using acetylated derivatives as donors and trimethylsilyl triflate as the catalyst. Intramolecular tosylate displacement to form 3,6-anhydro rings proceeded in methanolic sodium methoxide. PMID- 1596916 TI - Papulacandins and chaetiacandin: a stereoselective route to their basic skeleton by a palladium-mediated arylation of 4,6-O-benzylidene-3-O-tert- butyldimethylsilyl-l-tributyl-stannyl-D-glucal. AB - Palladium(0)-catalysed coupling of 1,5-anhydro-4,6-O-benzylidene-3-O-tert- butyldimethylsilyl-2-deoxy-1-tributylstannyl-D-arabino-hex-1-eni tol (7) with 3,5 dibenzyloxy-2-bromobenzyl alcohol gave 1,1(2)-anhydro-4,6-O-benzylidene-3-O-tert butyldimethylsilyl-2-deoxy-1-( 4,6- dibenzyloxy-2-hydroxymethyl-phenyl)-alpha-D arabino-hexopyranos e (13). The same reaction buffered by sodium carbonate provided 1,5-anhydro-4,6- O-benzylidene-3-O-tert-butyldimethylsilyl-2-deoxy-1 (4,6-dibenzyloxy+ ++-2- hydroxymethyl-phenyl)-D-arabino-hex-1-enitol (11). Stereoselective oxidative spiroacetalisation of 11 provided 1,1(2)- anhydro-4,6-O benzylidene-3-O-tert-butyldimethylsilyl-1-(4,6-dibenzyl oxy-2- hydroxymethyl phenyl)-alpha-D-glucopyranose (15), the basic tricyclic structure of papulacandins. In a model study, 15 was converted in three steps into 1,1(2) anhydro-1-(4,6-dihydroxy-2-hydroxymethylphenyl)-3-O- octadecanoyl-alpha-D glucopyranose (24), a structural analogue of papulacandin D. Moreover, stereoselective hydroboration-oxidation of 11 furnished 2-(4,6-O-benzylidene-3-O tert-butyldimethylsilyl-beta-D- glucopyranosyl)-3,5-dibenzyloxy-1 hydroxymethylbenzene (26), the structural skeleton of the chaetiacandin 3. PMID- 1596917 TI - Structural analysis of monosulfated side-chain oligosaccharides isolated from human tracheobronchial mucous glycoproteins. AB - To determine the location of some sulfate esters on respiratory mucins, an unambiguous sequencing strategy was developed for a crude, monosulfated oligosaccharide fraction derived from tracheobronchial mucous glycoproteins, isolated from sputum from a patient with cystic fibrosis, and which possessed Ricinus communis-I lectin affinity. Employing fractionation by Bio-Gel P-2 chromatography and high-voltage paper electrophoresis of the pool, eighteen branched and four straight-chained monosulfated oligosaccharides, each possessing at least one neutral D-galactose residue at a nonreducing terminus, were purified. Desulfated analogs of each sulfated oligosaccharide were then produced. Elucidation of their structures and sulfate ester locations was accomplished through a parallel comparative sequencing approach for the sulfated oligosaccharide and its desulfated analog. The method was based on their carbohydrate composition and parallel analysis by sequential exoglycosidase degradations, endoglycosidase digestion, permethylation analyses, and specific lectin affinities. Key to this approach was the inability for specific exoglycosidases and lectins to cleave or bind to, respectively, carbohydrates of their specificity which occupied nonreducing termini and possessed a sulfate ester. Herein we report the structures of twenty-two novel sulfated oligosaccharides. Oligosaccharides ranged from trisaccharides to heptasaccharides, were branched and unbranched, and each possessed a single sulfate ester on either C-6 of a terminal or an internal D-galactose residue or on C-6 of an internal residue of 2-acetamido-2-deoxy-D-glucose (N-acetyl-D glucosamine). PMID- 1596918 TI - 1H-N.m.r. study of enzymically generated wheat-endosperm arabinoxylan oligosaccharides: structures of hepta- to tetradeca-saccharides containing two or three branched xylose residues. AB - The structures of hepta- to tetradeca-saccharides, generated by digestion of wheat-endosperm arabinoxylan with endo-(1----4)-beta-D-xylanase, and isolated by gel-permeation chromatography on Bio-Gel P-6 and high-performance anion-exchange chromatography with pulsed amperometric detection (h.p.a.e.-p.a.d.), were elucidated using monosaccharide and methylation analysis, f.a.b.-m.s., and 1H n.m.r. spectroscopy. The structures identified had two branching elements, --- 4)[alpha-L-Araf-(1----3)]-beta-D-Xylp-(1---- and/or ----4) [alpha-L-Araf-(1--- 2)][alpha-L-Araf-(1----3)]-beta-D-Xyl p-(1----, directly connected to each other in all four possible combinations. The h.p.a.e.-p.a.d. elution pattern showed that these combinations are not present in equal amounts. Also, compounds containing two 2,3-branched beta-D-Xylp residues separated by one or two unbranched beta-D-Xylp residues were found, and the presence of a tetradecasaccharide containing three 2,3-branched beta-D-Xylp residues was established. PMID- 1596919 TI - Proteoglycans in human burn hypertrophic scar from a patient with Ehlers-Danlos syndrome. AB - Proteoglycans (PGs) from human burn hypertrophic scar of a patient with Ehlers Danlos syndrome were extracted with 4M guanidinium chloride and purified by DEAE cellulose chromatography. Differential ethanol precipitation of the PG fraction obtained after ion-exchange chromatography yielded two low mol.-wt. PGs, on rich in glucuronic acid (PGGLCA; Mr 66 kDa) and the other rich in iduronic acid (PGIDOA; Mr 48 kDa). In PGGLCA, 84% of the glycosaminoglycan chains are composed of GlcA----GalNAc(SO4) units, whereas in PGIDOA, the chains contain 95% IdoA--- GalNAc(SO4) disaccharide units. Upon treatment with testicular hyaluronidase, the PGs gave different-sized oligosaccharides. Chondroitinase ABC digestion of PGGLCA or PGIDOA gave a single protein core (Mr approximately 20 kDa). The presence of glucosamine and sialic acid in PGGLCA and PGIDOA suggests that both contain N linked oligosaccharides. PMID- 1596920 TI - The structure of mytilan, a bioglycan-immunomodulator isolated from the mussel Crenomytilus grayanus. AB - Mytilan, isolated from the mantle of the mussel Crenomytilus grayanus and which possesses high immunomodulating activity, is a non-covalently linked complex of a polysaccharide (95%) and protein (5%) with lectin activities. Chromatography of mytilan on agarose separated the polysaccharide and protein constituents. The protein appeared to have the lectin properties. Methylation analysis, Smith degradation, digestion with alpha-amylase, and 13C-n.m.r. spectroscopy showed the polysaccharide to be a glycogen-like alpha-D-glucan. PMID- 1596921 TI - Exopolysaccharides from Rhizobium meliloti YE-2 grown under different osmolarity conditions: viscoelastic properties. AB - The exopolysaccharides fro Rhizobium meliloti YE-2 extracted 10 days after the inoculum from culture broths and having different osmolarity values (0, 0.2, 0.4, and 0.6 M) have been investigated by means of oscillatory and steady-shear measurements on 1% solutions in 0.1M NaCl. The micro-organism produces a mixture of a galactoglucan and a succinoglycan. At low osmolarity (0 and 0.2M), the main fraction consists of galactoglucan and the viscoelastic properties of the mixture are typical of an entanglement system. At 0.4 and 0.6M, the proportion of the succinoglycan increases and the viscoelastic properties change abruptly to those typical of a "weak gel" system. Different conformations are adopted by the two exopolysaccharides in solution. PMID- 1596923 TI - Properties of the enzyme expressed by the Pseudomonas saccharophila maltotetraohydrolase gene (mta) in Escherichia coli. AB - The maltotetraohydrolase gene (mta) from Pseudomonas saccharophila was expressed in Escherichia coli JM109. Maltotetraohydrolase was produced mostly (approximately 90%) in the periplasmic space. The amino-terminal amino acid sequence and molecular weight of the recombinant enzyme were identical with those of the native enzyme, and there was no significant difference in the substrate specificity and modes of action. This system for maltotetraohydrolase expression is useful for studies of the structure and function of the enzyme. PMID- 1596922 TI - C-glycosyl compounds bind to receptors on the surface of Escherichia coli and can target proteins to the organism. AB - A series of C-mannopyranosyl derivatives have been synthesized and their inhibitory activity towards the receptor-mediated adhesion of E. coli to yeast cells has been tested. Total inhibition of yeast-cell agglutination by C-glycosyl derivatives 4 and 9 is achieved at a concentration approximately one order of magnitude lower than that of methyl alpha-D-mannopyranoside, indicating that the binding affinity to the receptor is related to the hydrophobicity of the carbon linked side chain. A biotin-linked C-glycosyl derivative of mannose (compound 9) has been synthesized and used to target avidin and streptavidin to the bacterial cell surface. Of the C-glycosyl derivatives tested in our study, the conjugate of compound 9 with avidin had the highest avidity for the bacterial receptors, inhibiting agglutination at a concentration three orders of magnitude lower than methyl alpha-D-mannopyranoside. The use of such bifunctional compounds as the mannose-biotin conjugate 9 is a general strategy to target molecules to pathogenic organisms via their cell-surface carbohydrate receptors and to change the antigenicity of the bacterial cell surface. PMID- 1596924 TI - Glucuronoxylomannan of Cryptococcus neoformans serotype D: structural analysis by gas-liquid chromatography-mass spectrometry and by 13C-nuclear magnetic resonance spectroscopy. PMID- 1596925 TI - Crystal and molecular structure of 5-azido-3-O-benzoyl-6-O- tert butyldiphenylsilyl-5-deoxy-1,2-O-isopropylidene-beta-L- talofuranose. PMID- 1596926 TI - Alternative synthesis and enzyme-inhibitory activity of methyl 1'-epiacarviosin and its 6-hydroxy analog. PMID- 1596928 TI - Preparation and characterisation of N epsilon-(1-deoxy-D-fructos-1-yl)hippuryl lysine. PMID- 1596927 TI - Multiple tritylation: a convenient route to polysubstituted derivatives of cyclomaltohexaose. PMID- 1596929 TI - Total synthesis of (+)-validamycin H. PMID- 1596930 TI - Isolation and structure of a 4-O-methyl-glucuronoarabinogalactan from Boswellia serrata. PMID- 1596931 TI - Hyaluronic acid and a (1----4)-beta-D-xylan, extracellular polysaccharides of Pasteurella multocida (Carter type A) strain 880. PMID- 1596932 TI - Crystal structure of lactitol (4-O-beta-D-galactopyranosyl-D-glucitol). AB - Lactitol, C12H24O11, is monoclinic, space group P2(1) with cell dimensions a = 7.614(1), b = 10.757(1), c = 9.370(1) A, beta = 108.19(1) degrees, and V = 729.0(1) A3, Z = 2, Dx = 1.57 Mg.m-3, lambda (Cu-K alpha) = 1.54056 A, mu = 1.166 mm-1, F(000) = 368, and T = 23 degrees. The structure was solved by direct methods and refined by least-squares calculations to R = 0.048 for 1510 unique observed reflections. There are one intra- and eight inter-molecular hydrogen bonds in the structure. Bond lengths and angles accord well with the mean values of related structures. The galactopyranosyl ring has a chair conformation. PMID- 1596933 TI - Crystal structure of lactitol (4-O-beta-D-galactopyranosyl-D-glucitol) dihydrate. AB - Lactitol dihydrate, C12H24O11.2H2O, is tetragonal, space group P4(3)2(1)2 with cell dimensions a and b = 8.7612(1), c = 45.500(3) A, and V = 3493.2(3) A3, Z = 8, Dx = 1.45 Mg.m-3, lambda (Cu-K alpha) = 1.54056 A, mu = 1.108 mm-1, F(000) = 1632, and T = 23 degrees. The structure was solved by direct methods and refined by least-squares calculations to R = 0.054 for 2037 unique observed reflections. There are three intra- and twelve inter-molecular hydrogen bonds in the structure. Bond lengths and angles accord quite well with the mean values of related structures. The galactopyranosyl ring has a chair conformation. PMID- 1596935 TI - Distribution of substituents in O-(2-hydroxypropyl) derivatives of cyclomalto oligosaccharides (cyclodextrins: influence of increasing substitution of the base used in the preparation, and of macrocyclic size. AB - Samples of O-(2-hydroxypropyl)derivatives of cyclomaltoheptaose (beta cyclodextrin) with increasing substitution were prepared by withdrawing aliquots at different times from a reaction mixture containing cyclomaltoheptaose and an excess of (S)-propylene oxide in 0.39 M aqueous sodium hydroxide. The distributions of substituents between the different molecules and between the different alpha-D-glucopyranosyl residues in these samples were determined by mass spectrometry and methylation analysis, respectively. The solubilities of the samples and their association constants with phenolphthalein were also determined. The relative reactivities at O-2 and O-3 versus O-6, calculated using Spurlin's equations, decreased with increasing degree of substitution, probably because of steric hindrance. No significant differences were observed when different strong bases were used as promoters of the hydroxypropylation of cyclomaltoheptaose. The hydroxypropylation of cyclomaltohexaose (alpha cyclodextrin) and cyclomalto-octaose (gamma-cyclodextrin) was briefly investigated. PMID- 1596934 TI - One- and two-dimensional 13C-n.m.r. characterization of two series of oligosaccharides derived from porcine intestinal mucosal heparin by degradation with heparinase. AB - Two tetrasaccharides, two hexasaccharides, and a disaccharide have been purified from heparinase digests of porcine intestinal mucosal heparin in sufficient quantities to permit 13C-n.m.r. characterization of the species. The two tetrasaccharides are the sulfated iduronic acid-containing 4en-HexpA2SO3-(1----4) alpha-D-GlcpNSO3;6SO3-(1- ---4)-alpha-L- IdopA2SO3-(1----4)-D-GlcpNSO3;6SO3 and the non-sulfated glucuronic acid-containing 4en-HexpA2SO3-(1----4)-alpha-D GlcpNSO3;6SO3-(1- ---4)-beta-D-GlcpA-(1----4)-D- GlcpNSO3;6SO3. The two hexasaccharides are related to the two tetrasaccharides by the insertion of alpha linked L-IdopA2SO3-(1----4)-D-GlcpNSO3;6SO3 after the non-reducing end sulfated glucosamine residue. The disaccharide is 4en-HexpA2SO3-(1----4)-alpha-D GlcpNSO3;6SO3. The disaccharide, together with each of the iduronate-containing oligosaccharides, form one series of related di-, tetra-, and hexa-saccharides, while the disaccharide together with the glucuronate-containing oligosaccharides form a second series. Using inverse detection as a means of increasing sensitivity, two-dimensional n.m.r. 13C-1H heterocorrelation spectra have been obtained for all five oligosaccharides. The use of two-dimensional heterocorrelation n.m.r. spectroscopy offers a much less ambiguous means of making 13C resonance assignments than do traditional one-dimensional methods, while the use of inverse detection gives both greater sensitivity than direct detection, as well as values for the one-bond 13C-1H coupling constants. From a knowledge of the assignments of resonances in the 1H spectra of these species, it has been possible to assign almost all of the 13C resonances of these five oligosaccharides. Some corrections to previously published assignments for the tetrasaccharides have been made. In addition, one-bond 13C-1H coupling constant data have been obtained for all of the anomeric protons. PMID- 1596936 TI - Idiotype network components are involved in the murine immune response to simian virus 40 large tumor antigen. AB - Baculovirus-derived recombinant simian virus 40 (SV40) large tumor antigen (SV40 T-Ag), a monoclonal antibody specific for SV40 T-Ag (Ab-1 preparation), and a monoclonal anti-idiotypic antibody (anti-Id), designated 58D, were used to analyze the humoral immune response of Balb/c mice either immunized with recombinant SV40 T-Ag or challenged with SV40-transformed cells. Inhibition assays indicated that antibodies from mice immunized with SV40 T-Ag and from those bearing SV40 tumor inhibited the SV40 T-Ag/Ab-1 reaction. These data suggested that the antibody response in immunized or tumor-challenged mice recognized similar epitope(s) on SV40 T-Ag to that detected by the monoclonal Ab 1. These anti-(SV40 T-Ag) response antibodies also inhibited the Ab-1/anti-Id reaction and recognized the anti-Id in direct binding assays. Together, these data indicate that murine anti-(SV40 T-Ag) responses shared an idiotope with a monoclonal anti-(SV40 T-Ag) Ab-1 preparation. This idiotope, which is recognized by the monoclonal anti-Id preparation, 58D, appears to be involved in the humoral immune response to SV40 T-Ag in both SV40-T-Ag-immunized and tumor-bearing mice. The monoclonal anti-Id preparation may represent a focal point for manipulating the humoral immune response to tumors induced by SV40-transformed cells. PMID- 1596938 TI - Promotion of murine antitumor activity by prothymosin alpha treatment: I. Induction of tumoricidal peritoneal cells producing high levels of tumour necrosis factor alpha. AB - The effect of prothymosin alpha (ProT alpha) on the survival of DBA/2 mice inoculated with syngeneic tumour cells was studied. DBA/2 mice inoculated intraperitoneally (i.p.) with 2 x 10(5) syngeneic leukaemic L1210 cells developed ascites within 8-12 days and died 10-14 days later. Treatment with ProT alpha consistently inhibited the development of ascites in 20% of the treated animals and prolonged the survival of 40%-60% of the animals up to 70 days. The most effective treatment schedule of ProT alpha was 300 ng/mouse given i.p. at 2-day intervals for 3 weeks followed by a rest period of 7 days, prior to tumour cell inoculation. Peritoneal exudate (PE) cells collected from mice treated with the optimal dose of ProT alpha produced, in the absence of exogenous stimulus, six- to eightfold higher levels of tumour necrosis factor alpha (TNF alpha) than PE cells from control mice. Furthermore these cells exhibited cytotoxic activity against several tumour cell lines including the syngeneic L1210, the TNF insensitive P815 mastocytoma, the human MOLT-4 lymphoblastic leukaemia, as well as the murine TNF-sensitive L929 fibroblast cell line. Kinetic studies revealed that both production of TNF alpha and tumoricidal activity peaked 7 days after the last injection of ProT alpha and were maintained at high levels over a period of 1 month. Injections with 150 ng ProT alpha slightly improved the survival of mice whereas higher (500 ng and 1000 ng) doses of ProT alpha and a wide range of thymosin alpha 1 doses remained without any effect. PE cells collected from these mice produced extremely low levels of TNF alpha and exhibited negligible tumoricidal activity. Our data demonstrate that ProT alpha has a protective effect in vivo against the growth of adoptively transferred tumour cells and suggest that this effect is, at least in part, mediated by ProT alpha-activated PE cells. These cells were demonstrated to produce high levels of TNF alpha in vitro and to exhibit activity against both TNF-sensitive and TNF-resistant cell lines. PMID- 1596937 TI - Chemo-adoptive immunotherapy of nude mice implanted with human colorectal carcinoma and melanoma cell lines. AB - The antitumor effects of chemotherapy, recombinant human interleukin-2 (IL-2), recombinant human interferon alpha A/D (IFN alpha), allogeneic human lymphokine activated killer (LAK) cells, and antitumor monoclonal antibody (mAb), administered alone and in various combinations, were tested in athymic nude mice carrying human tumor xenografts. Treatment began 6-18 days after i.v. or i.p. inoculation of colorectal carcinoma or melanoma cell lines, when macroscopic growths were evident. Chemotherapy consisted of two or three courses of 5 fluorouracil (5-FU) or dacarbazine. IL-2 and/or IFN alpha were administered three to five times weekly for 1-3 weeks, usually starting 2-5 days after chemotherapy. Human LAK cells were infused once or twice weekly for 2 or 3 weeks concurrently with IL-2. In some experiments, murine anticolorectal carcinoma mAb (SF25) was administered. In both tumor systems, chemotherapy alone or immunotherapy alone (IL-2, IL-2 + LAK cells, IFN alpha, IL-2 + IFN alpha +/- LAK cells) had little or no therapeutic effects. Additive effects were obtained by combining chemotherapy with IL-2 and LAK cells or with IL-2 and IFN alpha. In the majority of the experiments, the most effective combination was chemotherapy + IL-2 + IFN alpha + LAK cells. Treatment with mAb was beneficial in the colorectal carcinoma system when combined with 5-FU + IL-2 or 5-FU + IL-2 + IFN alpha. Homing experiments with radiolabeled human and mouse LAK cells injected i.v. showed increased early accumulation in the liver and lungs, whereas freshly explanted mouse splenocytes localized mostly in the spleen and liver. The tissue distribution pattern of human LAK cells was similar in normal and tumor-bearing mice (with lung metastases). These findings suggest that combination of chemotherapy with cytokines and LAK cells can be partially effective for advanced solid human tumors even in the absence of the host's T-cell immune response. Preliminary experiments showed that tumor-specific, anti-melanoma T-cell clones were effective in local (s.c.) tumor growth inhibition (Winn assay) following coinjection with the autologous tumor cells. PMID- 1596940 TI - [Relation of dementia, Alzheimer's disease and aging]. AB - Relation of dementia, Alzheimer's disease and brain aging was analyzed in a group of 50 persons who decreased at the age of 90 or more. Each of them were investigated according to 87 clinical a pathological variable features. The group has remained the world biggest for the time being. Final diagnosis of Alzheimer's disease is a histological one. Author proved that it depended on criteria lacking of world wide standardization. Various criteria could show the Alzheimer's disease as a phenomenon either not increasing in the 10th decade and differing from aging, or increasing and close or equal to aging. Statistical analysis of author's data could distinguish between non-demented and seriously demented individuals according to the number of plaques. A quasi-selective amnesia of old persons which is taken for a "benign senile forgetfulness" could be a sign of evolving Alzheimer's disease. Dementia is an unevitable condition for the diagnosis of Alzheimer's disease. This is without doubt important for a clinical diagnosis and not for a morphological expression of biological event. Author presume there exists an Alzheimer's disease under clinical threshold which combined with a clinically manifest disease does increase with the age and inflicts on 9 per cent of population in the 10th decade. Alzheimer's disease seems to be a fundamental biological event at least related to brain aging. A productive research problem might be to find out why "Alzheimer" features measured by common methods avoid 10 per cent of population in the 10th decade. PMID- 1596939 TI - Interleukin-6 and renal cell cancer: production, regulation, and growth effects. AB - Interleukin-6 (IL-6) is a recently characterized pleiotropic cytokine with antitumor activity. We investigated the production of IL-6 by renal cell cancer (RCC) and the growth effects of IL-6 on RCC. Using immunoperoxidase staining, cytoplasmic IL-6 was detected in four of four renal tumor lines and in tumor cells from freshly nephrectomized RCC. We found that IL-6 mRNA was expressed at basal culture conditions by seven of ten RCC tumor lines tested. Biologically active IL-6, as measured by the B9 assay, was produced by all ten RCC tumor lines. The addition of tumor necrosis factor alpha (TNF alpha) significantly augmented the expression of IL-6 mRNA in five RCC tumor lines (P less than 0.05). The combination of interferon gamma IFN gamma and TNF alpha further enhanced the augmented IL-6 mRNA accumulation seen with TNF alpha alone (P less than 0.05). TNF alpha also significantly stimulated the production of biologically active IL 6 (P less than 0.01). Furthermore, IFN gamma and TNF alpha were found to enhance IL-6 bioactivity synergistically (P less than 0.05). The growth effects of IL-6 on RCC were also investigated in two experimental systems: IL-6 was found to stimulate proliferative responses in six of six RCC tumor lines as measured by thymidine-uptake assays; however, only one of six tumor lines displayed an increase in proliferative response of greater than 21% (113%). The growth effect of IL-6 was further tested in clonogenic assays. One of the tumor lines tested displayed an enhanced growth response of up to 200%. We conclude that IL-6 is produced by RCC; this production is enhanced by TNF alpha with synergistic effects seen with IFN gamma at both mRNA and protein levels. In turn, IL-6 may have a modest stimulatory growth effect on certain RCC tumor lines. PMID- 1596941 TI - [Peroperative cytologic diagnosis]. AB - Author performed intraoperative cytology of 236 pneumomediastinal processes, 251 mammary and 45 other focal lesions. He used fine needle asperation or scraping of pathological tissue and hematoxylin-eosin staining of smears. Diagnosis of pulmomediastinal processes was reliable in carcinomas, chondrohartomas, and polymorphocellular sarcomas. Unreliability as to biological behaviour was found in identification of low grade malignant mesenchymal tumours which needed histology. Cytokeratin expression verified the diagnosis of thymoma from routine staining and enabled cytological and histological identification of extensive bronchioloalveolar epithelial hyperplasia associated with specific and unspecific inflammations or marginally with primary as well as secondary epithelial and mesenchymal malignant tumours and melanomas. Intraoperative cytology of mammary lesions succeeded in identification of nonmalignant processes and of 94 from 97 carcinomas (remaining 3 having been left for histology). As a rule, intraoperative cytology yielded a prompt information about investigated process' nature which was necessary for defining the extent of surgery, further information was completed by histology. PMID- 1596942 TI - [Distribution of periventricular necrosis and mild pathomorphologic changes in the brain in hypoxic-ischemic encephalopathy in neonates]. AB - An analysis of histotopographic sections from 31 neonatal brains with hypoxic periventricular necroses. Distribution and topography of necroses was traced in 7 frontal planes in correlation to frequency of impaired white matter tracts. Results were summarized in schemes. Another topic of analysis was morphology of a slight white matter impairment (spongiosis). Used three grade classification of slight white matter impairment contributed to morphologic criteria of neonatal hypoxic-ischemic encephalopathy. Having considered his own findings and data from literature the author decided a standard histological tissue sampling for perinatal encephalopathies. PMID- 1596943 TI - [Cytodiagnosis of bone tumors]. AB - Fine needle biopsy was performed in 48 patients suffering from X-ray detected osteolytic lesions, during two years. A representative sample was obtained in 38 of them (79.2 percent). Cytologic conclusions could be proved in 35 patients by histology or clinical finding of primary tumour (in cases with bone secondaries). Cytologic diagnosis was correct in 30 patients (87.7 per cent). Especially good results were found out in bone metastases, plasmacytomas, and Ewing's sarcomas. Fine needle biopsy is to be recommended as an integral part of complex diagnosis of bone tumours. PMID- 1596944 TI - [Beta 2-microglobulin amyloidosis]. AB - A 35-year-old man who had been treated by hemodialysis for 15 years suffered from systemic amyloidosis. It was identified as a beta 2-microglobulin type according to immunohistochemistry. Extensive amyloid deposits were found in myocardium, cartilages of intervertebral discs and in carpal tunnel ligament. Less conspicuous deposits comprised blood vessels of lungs, liver, suprarenal glands, brain, and stroma of prostate gland, testicles, kidney, often combined with calcified foci. PMID- 1596945 TI - [Tumor-related partial pseudocirrhosis of the liver]. AB - Unusual sort of breast carcinoma metastases to the liver, combined with pseudolobular transformation, was found in an autopsy of 68-year-old female after complete oncological treatment. Nodes of parenchyma in abundant connective tissue nearly consisted of tumour cells. Terminology and pathogenesis were discussed. PMID- 1596946 TI - [Liver cirrhosis in surgical samples]. AB - 1729 liver excisions from patients with laparotomy (1302 women, 427 men) were analyzed during 5 years (1984-1988). There were 12 cirrhoses among them (in 6 women and 6 men) with medium history of about 5 years. HBsAg was proved both according to Shikata and immunohistochemically in 4 cirrhoses, two of them were serologically positive, only one known before operation. A case of seroconversion was observed (repeated seronegativity with histochemical and immunochemical HBsAg positivity). Men: women ratio of 3:1 correlated with the literature as well as the prevalence of macronodular and mixed cirrhosis in women and micronodular cirrhosis in men. Paper points out an infection risk in surgical staff operating on cases with unrevealed HBsAg positivity. PMID- 1596947 TI - [Differential diagnosis in early muscular hypotonia: spinal atrophy]. AB - Changes in type, size and structure of muscle fibres were analyzed in 68 biopsies with clinical and morphological signs of spinal atrophy. Reliability of clinical prebioptic diagnosis was evaluated in comparison with bioptic finding and final diagnosis. Muscle biopsy is often to be performed in spite of apparently unambiguous clinical and electromyographical finding. Contribution of biopsy to the diagnosis of spinal atrophy with characteristical grouping of atrophic fibres is undisputable in most cases. However, unproper sampling in excessively atrophic areas and structural "myogenic" changes can made the bioptic diagnosis difficult or impossible. Size analysis of muscle fibres proved participation of both the basic fibre types in atrophy with increase in number of immature type 2c fibres, and prevalence of type 1 fibres in hypertrophic areas (compensatory hypertrophy or re-innervation respectively) where also hybrid fibres can often be found during transformation of their type. Angular atrophic fibres occurring in hypertrophic fibre groups gave evidence of continuous or secondary denervation in benign forms of spinal atrophy. The author found regressive structural changes in benign form and in malignant Werdnig-Hoffman atrophy either--though less extensive. PMID- 1596948 TI - [Study of the contamination of hands in burn wards during intramuscular injections]. PMID- 1596949 TI - [Effect of small dosage of intradermal inoculation of hepatitis B vaccine in infants]. PMID- 1596950 TI - [Psychological care of sudden deafness patients]. PMID- 1596951 TI - [5 new cases of entomophthoromycosis observed in Cameroon. Role of immunofluorescence in thr diagnosis]. AB - The authors present five new cases of entomophthoromycosis observed during three years of histopathology in Cameroon. Three classic cases of rhinoentomophthoromycosis. In one case, Conidiobolus coronatus was isolated. Two cases of subcutaneous entomophthoromycosis, without isolation of the germ. In one observation, the clinical and histological aspect suggested mucormycosis post entomophthoromycosis. An immunofluorescence technique showed the Basidiobolus haptosporus to be the real cause. PMID- 1596952 TI - [Adenylate cyclase. A possible factor in the pathogenicity of Yersinia pestis]. AB - Biological effect of homogenous preparation of Y. pestis adenylate cyclase on eucaryotic cells was studied. Adenylate cyclase, added (7.5 x 10(8) g/ml) to guinea pig macrophages lowers the level of chemiluminescence to 50-70%, has an appreciable cytotoxic effect on peritoneal macrophages and suppresses phosphorylation processes of leucocyte proteins from white mice. The experimental results obtained allow to suggest Y. pestis adenylate cyclase to be a pathogenic factor, contributing to the development of plague infection. PMID- 1596953 TI - [Leprosy in Guadeloupe 1980-1990: development and management in the general hospital]. AB - 27 leprosy patients (19 adults, 8 children) from Basse Terre (Guadeloupe, FWI) were referred to General Hospital from 1975 to 1989: for diagnostic purpose in half the cases, for starting or modifying treatment regimens, or for complications (ENL). Lepromatous type was predominant (16/27), whereas ENL was the most serious diagnosis and therapeutic problem (7/27). Some epidemiological and psycho-social aspects are discussed. PMID- 1596954 TI - [Malaria in Yaounde (Cameroon). Cost and antivectorial control at the family level]. AB - In order to evaluate the financial charges of antivector control and disease at family level for "malaria disease" as perceived by Yaounde inhabitants, the authors carried out a transverse survey on a representative sample of populations derived from sampling surveys at different degrees. Malaria, so defined, represents a dominating endemic for which the yearly financial effort consented by each family amounts to 57,000 FCFA which represents medical care and entailed services as well as the purchase of chemicals for antivector control. The development of more efficient therapeutic behaviours and promotion of greater use of remanent insecticide impregnated bed nets comes in first in setting up training programmes aimed at health personnels and populations who are under their responsibility. PMID- 1596955 TI - [Current recrudescence of human trypanosomiasis in the Sangha focus (basin) in the Congo]. AB - In the Congo the Sangha focus of sleeping sickness caused more than 500,000 deaths in the early 20th century. Despite many years of quiescence many new cases have been detected since the early eighties. In 1987 an investigation found 43 infected patients within 5 villages (during the same year, 74 cases were detected from both investigation and passive detection). In December 1989 our further investigation found 96 new documented cases (115 for the whole year). The prevalence is increasing and the proportion of early stage in comparison with later stage is decreasing. The age diagram resembles that of the early 20th century. Despite the fact that the survey in 1989, extracted twice as many patients as in 1987 passive detection detected 99 infected patients in 1990, three times as many cases as in 1988, and places the "Sangha focus" in IId place in the Congo, after the "Bouenza focus". As only river transport is available to have access to that focus, the Congo will be faced with considerable difficulties in the future. PMID- 1596956 TI - [Presence of abdominal angiostrongylosis in Guadeloupe. Apropos of 2 recent cases]. AB - The authors describe the first two cases of abdominal angiostrongylosis in Guadeloupe, confirmed by a histological analysis. Physicians must be aware of the presence of Angiostrongylus costaricensis in the West Indies in order to provide better care for children presenting with fever, abdominal pain and rectorragiae, along with intense biological markers of inflammation. PMID- 1596957 TI - [Intestinal parasitism in the adult. Evaluation of 2 years in the University Hospital Center of Sfax]. AB - From copro parasitologic analyses of two years studied between December 1988 and 1990 in the Hospital Center of the University of Sfax, the authors determined the intestinal parasites profile observed in adults. This intestine parasitism is mainly of protozoair type dominated by the amebae and Giardia intestinalis. The helminthes are rarely found. Strongyloides stercoralis of an epidemiology unknown in the region was revealed in some patients submitted to an immunosuppressive therapy. The adult cestodes as well as in Child doesn't seen to constitute a major parasitism in Sfax. PMID- 1596958 TI - [Tolerance of ivermectin treatment of rural communities infected by savannah onchocerciasis in Mali]. AB - In an open clinical trial in phase IV, 856 onchocerciasis infected subjects received 150 micrograms/kg of ivermectin in May 1987. While 607 were included as witness. This cohort was revisited 7 and 12 months after. In June 1988, the same treatment was administrated to the previously treated subjects, and the witnesses received their first ivermectin' dose. The clinical tolerance of the treatment appears good and, even improved during the second dose one year after. Among the subjects treated in May 1987, 15.2% of them showed secondary reactions mostly discrete or moderate, precocious and quickly reversible after a second dose. Only 8 of them were incommodated in their daily occupations. A second treatment of these same subjects one year later, caused reactions of feeble intensity 3.7% only. The research of intolerance risk factors, incriminated the high density of microfilaremia. This incite to be careful in mass treatment of hyperendemic area. PMID- 1596959 TI - [Transmission of hepatitis B virus from mother to child in Bamako-Mali]. AB - Results of a study about mother-infant transmission of hepatitis B virus (HBV) confirm the high degree of positivity of HBV markers in Bamako, Republic of Mali. Among 372 sera of mother-newborn pairs, seroprevalence of HBs Ag has been around 11% in mothers. The lack of anti HBc IgM in all sera agree probably with a relative old contamination. Pre-S2 epitope marker has been found in more than 70% of HBs Ag positive mothers and 50% of their children. Large discordance has been noted between the prevalence rate of this marker and the HBe Ag and viral DNA, other markers of HBV replication. Further studies are necessary for the clear understanding of HBV transmission systems in our country. PMID- 1596960 TI - [2 infectious granulomatous diseases (leprosy and cutaneous and mucous leishmaniasis) by scintigraphic methods]. AB - Leprosy is a multiform chronic infectious granulomatous disease caused by Mycobacterium leprae, that affects over 12 million people in the world. Cutaneous and mucous leishmaniasis (CML) is also a chronic granulomatous infectious disease, caused by Leishmania brasiliensis and transmitted to man by the mosquitoes of the Phlebotominae family. It is a worldwide spread disease. We studied one case of Borderline-wirchowian leprosy and 2 cases of CML with Gallium 67 (GA-67) scintigraphy. Ga-67 is a radiopharmaceutical known for its property of concentrating in inflammatory sites. In the leprosy patient, Ga-67 accumulated in the skin in a moderate, homogeneous and disseminated way (outlined skin); in the area of the face, the uptake was important and homogeneous (image in beard). Several internal organs accumulated Ga-67. As for the 2 CML patients, Ga-67 accumulated focally, in different degrees, in the affected anatomical areas. The leprosy patient was not under treatment and the 2 CML were under treatment (20 and 40 days, respectively). In the 3 cases, all affected areas accumulated Ga-67. Intensity differences of uptake may be explained both by different degrees of inflammatory processes (between leprosy and CML) and by treatment lasting. It is possible that Ga-67 scintigraphy may be useful for the evaluation of these 2 diseases extent and also for the therapy follow-up. PMID- 1596961 TI - [Urban malaria in Yaounde (Cameroon). 2. Entomologic study in 2 suburban districts]. AB - A one year entomological survey was carried out to precise the malaria vectors and the malaria transmission in Yaounde, the Cameroon capital (800,000 inhabitants). The study was done in two districts not yet fully urbanized: Nkol Bikok and Nkol Bisson. The latter is located at the periphery and has a pool. Anopheles gambiae was the only human malaria vector. Its agressivity for man depended on the urbanization of the district. Annual man biting rate was 284 in Nkol Bikok and 1,813 in Nkol Bisson. The densities were maximum in May-June and in October-November, corresponding to the end of the short and long rainy seasons. The presence of A. gambiae was permanent except in August-September in Nkol Bikok. In Nkol Bisson the density was higher in the houses near the pool. The yearly inoculation rate (h) was 14 in Nkol Bikok and 30 in Nkol Bisson. The vectorial transmission was observed in may in Nkol Bikok and during four months (June, August, January, February) in Nkol Bisson. These entomological data showed clearly that malaria transmission actually occurred in Yaounde and that the probability to receive at least one infected anopheline bite per year was very near to 1 for inhabitants unprotected against mosquito bites. PMID- 1596962 TI - [Distribution and importance of sites of Glossina fuscipes fuscipes Newstead 1910 in the agglomeration of Bangui (Central Africal Republic)]. AB - The authors review urban sites of Glossina fuscipes fuscipes in the suburbs of Bangui and propose a classification of these sites. Among them, two isolated breeding sites are characterized by a high density of tsetse and a close man/fly contact. To prevent a possible reactivation of the historical sleeping sickness focus of Bangui-Bimbo, a tsetse control programme in these two sites is necessary. PMID- 1596963 TI - [Histology of insect infection by entomopathogenic fungi: interest in a new procedure for the study of precocious phases]. AB - Infective and invasive processes of entomopathogenic fungi expected to be used in biological control shall be analysed in detail. Histological and ultrastructural studies are therefore essential. This paper is devoted to the field of light microscopy; its purpose is to show that coating, in a 4% agar solution, the insects infected by a fungus, prior to fixation and embedding, allows the preservation of the fungal structures present on the cuticle, especially the germinating conidia. This is useful when observing the initial stages of infection. The relevance of this coating technique is illustrated with the example of Pea aphid, Acyrthosiphon pisum, infected by Conidiobolus osmodes. This contribution is the first histological study of infective processes of this entomophthoralean fungus in an insect. PMID- 1596964 TI - [Autochthonous malaria in Brittany]. PMID- 1596965 TI - Anaesthesia research: needs for the nineties. PMID- 1596966 TI - The Canadian four-centre study of anaesthetic outcomes: II. Can outcomes be used to assess the quality of anaesthesia care? AB - Since anaesthesia, unlike medical or surgical specialties, does not constitute treatment, this study sought to determine if methods used to assess medical or surgical outcomes (that is the determination of adverse outcome) are applicable to anaesthesia. Anaesthetists collected information on patient, surgical and anaesthetic factors while data on recovery room and postoperative events were evaluated by research nurses. Data on 27,184 inpatients were collected and the analysis of outcomes determined for the intraoperative, post-anaesthetic care unit and postoperative time periods. Logistic regression was used to control for differences in patient populations across the four hospitals. In addition, a random selection of 115 major events was classified by a panel of anaesthetists into anaesthesia, surgical and patient-disease contributions. Across the three time periods, large variations in minor outcomes were found across the four hospitals; these variations ranged from two- to five-fold after case-mix adjustment (age, physical status, sex, emergency versus elective and length of anaesthesia). The rates of major events and deaths were similar across three hospitals; one hospital had a lower mortality rate (P less than 0.001) but had a higher rate of all major events (P less than 0.0001). Of major events assessed by physician panels, 18.3% had some anaesthetic involvement and no deaths were attributable partially or wholly to anaesthesia. Possible reasons to account for these variations in outcome include compliance in recording events, inadequate case-mix adjustment, differences in interpretation of the variables (despite guidelines) and institutional differences in monitoring, charting and observation protocols. The authors conclude that measuring quality of care in anaesthesia by comparing major outcomes is unsatisfactory since the contribution of anaesthesia to perioperative outcomes is uncertain and that variations may be explained by institutional differences which are beyond the control of the anaesthetist. It is suggested that minor adverse events, particularly those of concern to the patient, should be the next focus for quality improvement in anaesthesia. PMID- 1596967 TI - The Canadian four-centre study of anaesthetic outcomes: III. Are anaesthetic complications predictable in day surgical practice? AB - To understand better the factors important to the safety of anaesthesia provided for day surgical procedures, we analyzed the intraoperative and immediate postoperative course of patients at four Canadian teaching hospitals' day treatment centres. After excluding those who received only monitored anaesthesia care, there were 6,914 adult (non-obstetrical) patients seen over a twelve-month period in 1988-89. The rate of adverse outcome consequent to their care was identified by a comprehensive surveillance system which included review of anaesthetic records (four hospitals) and follow-up telephone calls (two hospitals). The relationship between adverse events and preoperative factors was determined by using a multiple logistic regression analysis that included age, sex, duration of the procedure and the hospital care. There were no deaths during the study period and major morbid events were infrequent. Patient preoperative disease was predictive of some intraoperative events relating to the same organ system, but not to events in the PACU. Some unexpected relationships emerged including preoperative hypertension being related to a greater risk of difficult intubation, and neurological disease to perioperative cardiac abnormalities. Patients judged obese, or inadequately fasted, were found to experience a greater rate of recovery problems as well as discomfort. While the low response rate (36%) to the telephone interviews created a sampling bias, the high rate of patient dissatisfaction among those reached is disconcerting. We conclude that day surgical patients with preoperative medical conditions, even when optimally managed, are at higher risk for adverse events in the perioperative period. PMID- 1596968 TI - Adequacy of caudal analgesia in children after penoscrotal and inguinal surgery using 0.5 or 1.0 ml.kg-1 bupivacaine 0.125%. AB - To determine the optimal volume of bupivacaine 0.125% for postoperative caudal analgesia, we compared the effectiveness of 0.5 ml.kg-1 and 1 ml.kg-1 of bupivacaine 0.125% with 1:200,000 epinephrine in 80 children undergoing penoscrotal and inguinal surgery. The adequacy of caudal analgesia and supplemental analgesic requirements did not differ between the two groups at any time during the first 12 hr after surgery. We conclude that 0.5 ml.kg-1 of bupivacaine 0.125% with 1:200,000 epinephrine is as effective as 1 ml.kg-1 of the same solution and recommend its use for penoscrotal surgery. The evidence for effectiveness of 0.5 ml.kg-1 of bupivacaine 0.125% for inguinal surgery, however, is inconclusive because of an insufficient number of patients studied. PMID- 1596969 TI - Tongue oximetry in children with extensive thermal injury: comparison with peripheral oximetry. AB - We undertook a prospective study of standard peripheral pulse oximetry versus a modified pulse oximeter probe applied to the tongue in order to determine the efficacy of this alternative monitoring site in children with thermal injuries. Ten patients with a mean age (+/- SD) of 7.5 +/- 4.5 yr were studied on 15 occasions. The mean weight (+/- SD) was 31.4 +/- 13.7 kg and percent surface area burn (+/- SD) was 56 +/- 21%. A total of 1,992 min of anaesthesia time was monitored. Both sites functioned simultaneously 47% of the time; the lingual but not the peripheral site functioned 28% of the time and only the peripheral site and not the lingual functioned 22% of the time. Neither site functioned 3% of the time. The tongue oximeter provided 563 min more monitoring time than the peripheral sites. The tongue oximeter also functioned in children with peripheral vasoconstriction when the peripheral sensor failed and was less susceptible to electrocautery interference. The tongue oximeter is a reasonable adjunct but not a substitute for peripheral oximetry since its application is limited to paralyzed, intubated patients. PMID- 1596970 TI - Respiratory mechanical properties during fentanyl and alfentanil anaesthesia. AB - The purpose of this study was to assess the effects on respiratory mechanics of fentanyl and alfentanil in 20 subjects to be submitted to coronary artery bypass grafting. Using the end inflation occlusion method (EIOM) we obtained the elastance (E) and resistance (R) of the total respiratory system (rs), thoracic wall (w) and lungs (L). The total respiratory system was divided into thoracic wall and lungs by using an oesophageal catheter. The data were recorded before, immediately after, and two, five and ten minutes after fentanyl and alfentanil iv bolus, at doses of 30 and 120 micrograms.kg-1, respectively. The Ers increased at two, five and ten minutes and the EL at ten minutes after drug administration. The Rrs,min and RL,min increased at two, five and ten minutes and the RL,max at five and ten minutes. Both drugs provoked no change in Ew or Rw. It is concluded that the increased in Rrs,min and RL,min could be explained by opioid bronchoconstriction. No differences were found between the effects of fentanyl and alfentanil on respiratory mechanics. PMID- 1596971 TI - Gastroesophageal reflux during anaesthesia. AB - While the number of patients at risk for vomiting and aspiration has been reported to be high, the incidence of clinically important pulmonary aspiration is low. We sought to define the incidence of gastroesophageal reflux (GER) and to correlate this with the clinical variables of obesity, history of oesophagitis, bucking and changes in body position. Continuous oesophageal pH measurement was used to determine the frequency of gastroesophageal reflux in 44 patients having general anaesthesia for elective surgical procedures. Acid reflux to a pH value of less than four occurred in seven patients (15.9%) during anaesthesia. This was associated temporally with straining on the endotracheal tube in six subjects (13.6%). We conclude that traditional risk factors are not always predictive of those patients at risk of regurgitation and aspiration. PMID- 1596972 TI - Assessment of behavioural objectives in anaesthesia resident training. AB - Residency training must be based on a comprehensive curriculum. Educators use the term behavioural objectives to represent educational objectives stated as behaviours that must be accomplished by the students. Educational objectives represent an important part of the curriculum content. However, curriculum content, as defined in large academic departments, has often been described as irrelevant for practitioners outside these large centres. Behavioural objectives drawn for the year of internal medicine, the fourth year of a five-year specialty programme in anaesthesia, were evaluated for their clinical relevance for anaesthetists in clinical practice outside cities where teaching programmes are found in the province of Quebec. A questionnaire based on 288 objectives, using a rating scale, was used to compare the opinions of the members of the Education Committee (6) and outside practitioners (24). There were no significant differences between the mean ratings of the two groups of raters on ten of the 14 groups of objectives. A concordance of opinion was also present when there was disagreement with the importance of certain objectives. There was disagreement with only one group (VIII) of objectives on 14. Within this group there was agreement with the clinically oriented objectives and disagreement with the laboratory oriented objectives. Objectives that were related to the acute aspects of illness were rated higher than those related to their chronic aspects. The outside practitioners made 81 suggestions or comments about the objectives. PMID- 1596973 TI - Anaesthesia and myasthenia gravis. AB - Myasthenia gravis is an autoimmune disease, resulting from the production of antibodies against the acetylcholine receptors of the endplate. These antibodies reduce the number of active receptors, brought about either by functional block of the receptors, by increased rate of receptor degradation, or by complement mediated lysis. In myasthenic muscles, the miniature endplate potential amplitude is decreased, and a large proportion of the endplate potentials are subthreshold. Repetitive nerve stimulation results in a decremental response. The disease is frequently associated with morphological abnormalities of the thymus. In young patients, thymic hyperplasia is common while thymoma is more frequent in elderly patients. Medical treatment of myasthenia gravis aims at improving of neuromuscular transmission by anticholinesterases, suppressing the immune system by corticosteroids and immunosuppressants, or by decreasing the circulating antibodies by plasmapheresis. Adults with generalized myasthenia should have a trans-sternal thymectomy. A balanced technique of general anaesthesia which includes the use of muscle relaxants can be safely used, provided neuromuscular transmission is monitored. Myasthenic patients are sensitive to nondepolarizing relaxants but intermediate-acting nondepolarizing relaxants such as atracurium and vecuronium are eliminated rapidly, and can be titrated to achieve the required neuromuscular block that can be completely reversed at the end of surgery. Postoperatively, ventilatory support may be required in high-risk patients. Also, medical treatment may be maintained, tapered or discontinued depending on the outcome of surgery. Thymectomy benefits nearly 96% of patients, 46% develop complete remission and 50% are asymptomatic or improve on therapy. PMID- 1596974 TI - Obstetrical anaesthesia and analgesia in chronic spinal cord-injured women. AB - Improved acute and rehabilitative care and emphasis on integrating patients into society after spinal cord injury is likely to result in increasing numbers of cord-injured women presenting for obstetrical care. Anaesthetists providing care to these women should be familiar with the complications resulting from chronic cord injury and aware that many may be aggravated by the physiological changes of normal pregnancy. These complications include reduced respiratory volumes and reserve, decreased blood pressure and an increased incidence of thromboembolic phenomena, anaemia and recurrent urinary tract infections. Patients with cord lesions above the T5 spinal level are at risk for the life-threatening complication of autonomic hyperreflexia (AH) which results from the loss of central regulation of the sympathetic nervous system below the level of the lesion. Sympathetic hyperactivity and hypertension result in response to noxious stimuli entering the cord below the level of the lesion. Labour appears to be a particularly noxious stimulus and patients with injuries above T5 are at risk for AH during labour even if they have not had previous AH episodes. Morbidity is related to the degree of hypertension and intracranial haemorrhage has been reported during labour and attributed to AH. We report our experience in providing care to three parturients with spinal cord injuries. Two patients had high cervical lesions, one of whom experienced AH during labour and was treated with an epidural block. The second was at risk for AH having had episodes in the past and received an epidural block to provide prophylaxis for AH. In both cases epidural blockade provided effective treatment and prophylaxis for AH.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1596975 TI - [Spontaneous splenic rupture disclosing a pheochromocytoma]. AB - Clinical manifestation of a phaeochromocytoma may range from no symptoms to an acute abdominal emergency. These abdominal emergencies are related to haemorrhagic necrosis of the tumour, or massive bleeding in the retroperitoneal space. The authors report a case of splenic rupture revealing a phaeochromocytoma. The mechanism of splenic rupture is discussed as is the conservative treatment of phaeochromocytoma during splenic surgery. The authors observed no correlation between plasma catecholamine concentration and blood pressure. PMID- 1596976 TI - Ulnar nerve palsy at the elbow after general anaesthesia. AB - Ulnar nerve palsy is a recognized complication of general anaesthesia. Many authors have reported several series of patients and found different incidences. In this literature review, the patho-physiology of the lesion and the anatomical characteristics of the cubital tunnel at the elbow are described together with its related conditions "cubital tunnel compression syndrome" and "recurrent ulnar nerve dislocation at the elbow." A precise and early diagnosis should be made using electromyography to determine the exact location of the lesion and the precise time-relationship of the pathology. The importance of careful positioning of the patient under anaesthesia in the prevention of ulnar nerve palsy is stressed. Unfortunately, treatment of the established lesion gives, at best, mixed results. PMID- 1596978 TI - Fibreoptic laryngoscopy after thyroid surgery. PMID- 1596977 TI - Reconstituted thiopentone retains its alkalinity without bacterial contamination for up to four weeks. AB - The manufacturers of thiopentone recommend that after reconstitution, it should be kept only for 24 hr to reduce the risk of contamination. However, there are no studies to support this practice and compliance with this recommendation has economic implications. The reasons for discarding a reconstituted bottle of thiopentone are related to concerns about chemical and physical (pH) stability, contamination with infectious agents, and contamination with cellular material. We studied the incidence of bacterial contamination and pH stability of thiopentone in clinical use, as well as the pH stability of thiopentone not in clinical use, and surveyed the eight hospitals affiliated with the University of British Columbia to determine their protocols for thiopental preparation and storage. Cost comparisons were made between our current practice of discarding thiopentone when depleted and the practice of routinely discarding it 24 hr after reconstitution. Samples of thiopentone in clinical use were cultured daily and the pH was measured. The bottles had been in clinical use from 1 to 25 days (mean 4.23 +/- 4.32 SD). Of 106 samples there were no positive bacteriological cultures and there were only minor changes in pH. The telephone survey of the eight hospitals revealed that only one had a policy to discard thiopentone after 24 hr. Cost comparisons indicate that discarding thiopentone 24 hr after reconstitution would result in increased cost. In conclusion, reconstituted thiopentone retains its alkalinity for up to four weeks, and has an acceptably low risk of bacterial contamination for periods beyond 24 hr, therefore thiopentone need not be discarded after 24 hr. PMID- 1596979 TI - Bullard laryngoscopy for tracheal intubation of patients with cervical spine pathology. PMID- 1596980 TI - Does propofol-nitrous oxide anaesthesia provide autonomic hyperreflexia (AH) prophylaxis in susceptible patients? PMID- 1596981 TI - Hazardous modification of Bain breathing attachment. PMID- 1596982 TI - Intubation and cervical spine injury. PMID- 1596983 TI - Uncommon laryngeal mask obstruction. PMID- 1596984 TI - The laryngeal mask airway as an aid to blind orotracheal intubation. PMID- 1596985 TI - Needle stick injuries. PMID- 1596986 TI - Continuous intercostal nerve block following thoracotomy. PMID- 1596987 TI - Tumour invasion of the brachial plexus: management of pain with intrapleural analgesia. PMID- 1596988 TI - Oral clonidine preanaesthetic medication does not alter plasma lidocaine elimination during epidural anaesthesia in lightly anaesthetized patients. PMID- 1596989 TI - Comparison of three bone alkaline phosphatase quantification methods in patients with increased alkaline phosphatase activities. PMID- 1596991 TI - Determining total protein content of urine: centrifugation results in precipitation of the protein-coomassie brilliant blue dye complex. PMID- 1596990 TI - Laboratory values in fit aging individuals--sexagenarians through centenarians. AB - We determined approximately 15,000 laboratory values in 236 individuals between the ages of 60 and 90 y, 22 individuals between 90 and 99 y, and 69 individuals greater than or equal to 100 y, and compared these with values in young adults. We tested 47 different analytes in the 60-90-y group and 93 analytes in the greater than or equal to 90-y group. Na, K, Cl, and CO2 values were either identical or showed minimal change with age; pH decreased slightly. Differences in Ca values were only minor, but ionized Ca increased slightly. Phosphate decreased in men, but changed only minimally in women; parathyroid hormone increased with age. Increases with age were also observed for glucose, insulin, and C-peptide. Among the enzymes, alkaline phosphatase increased in women, but in men only greater than 90 y; gamma-glutamyltransferase increased in both sexes. Creatine kinase (CK) decreased slightly in individuals greater than 70 y and markedly in those greater than 90 y of age, whereas CK-MB decreased markedly greater than 70 y, reaching the detection limit in individuals greater than 90 y. Lactate dehydrogenase isoenzyme 5 decreased slightly with age. Urea nitrogen increased gradually with age, but creatinine increased only in individuals greater than or equal to 90 y. The increase in urea is not paralleled by a loss of protein in urine, suggesting that the possible cause of azotemia may not always be renal pathology. Urate increased in women but not in men. Liver function, as measured by total bilirubin and liver enzymes, was exceedingly well maintained. Concentrations of most proteins show little change, except for slight decreases in prealbumin, albumin, and transferrin, proteins used as an index of nutritional status. IgA values increased, IgG ranges were wider, IgM and IgD decreased, and the range for IgE was narrower than in young adults. Cholesterol, high-density lipoprotein cholesterol, and triglyceride values increased with age, but decreased in individuals greater than or equal to 90 y. Among the trace elements, magnesium changed little, zinc and lead decreased, and copper values increased with age. Total triiodothyronine and thyroxine decreased, with concomitant increases in thyroid-stimulating hormone. More individuals had increased microsomal antibodies and thyroglobulin titers in the aging population than in the young. In men, the free, percent free, bioactive, and total testosterone values decreased, but luteinizing hormone (LH) and follicle stimulating hormone (FSH) values increased. In women, estrone and estradiol values decreased, with concomitant increases in LH and FSH. Androstenedione and progesterone decreased in both sexes.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1596992 TI - Contaminating DNA in RNA amplification by polymerase chain reaction. PMID- 1596993 TI - Comparison of cyclosporine blood concentrations measured by radioimmunoassay and two nonisotopic immunoassays using monoclonal antibodies. PMID- 1596994 TI - Cancer antigen 125 in patients with liver diseases. PMID- 1596995 TI - Simultaneous determination of retinol and tocopherols by HPLC. PMID- 1596996 TI - Cholesterol measurements in patients' sera stored at 4 or -20 degrees C for 24 h before analysis with a Kodak Ektachem 700 analyzer. PMID- 1596997 TI - Plasma selenium in congestive heart failure. PMID- 1596998 TI - Abnormal blood-ethanol profile associated with stress. PMID- 1596999 TI - S-troponin-T as a marker of ischemic myocardial injury. PMID- 1597000 TI - Chelation with ferric ions may prevent extraction of 2-hydroxydesipramine from whole blood. PMID- 1597001 TI - Effect of processing time and storage on fibrinogen content of EDTA plasma assayed by radial immunodiffusion. PMID- 1597002 TI - Plasma amino acid patterns in cancer. PMID- 1597003 TI - Apolipoprotein A-containing lipoprotein particles: physiological role, quantification, and clinical significance. AB - High-density lipoprotein (HDL) particles are made up of two major populations of particles, differing in composition and metabolism. Both contain apolipoprotein (apo) A-I but only one contains apo A-II. Lipoprotein particles that contain only apo A-I (LpA-I particles) can increase cellular cholesterol efflux from cultured cells in vitro. LpA-I:A-II particles, however, do not increase cholesterol efflux. LpA-I:A-II can be determined directly with an enzyme-linked differential antibody immunosorbent assay. LpA-I is determined by differential electroimmunoassay: in the presence of a large excess of anti-apo A-II, LpA-I:A II particles are retained in one peak, whereas LpA-I migrates grates as a second peak. Both lipoprotein forms of apo A-I-containing particles are present mainly in HDL, but the relative proportion of LpA-I is greater in HDL2 than in HDL3. Concentrations of LpA-I in plasma samples from normolipemic subjects average approximately 10% higher in women than in men. The lower apo A-I concentrations in patients with significant coronary artery disease reflect a decrease in the LpA-I particles. Data obtained in octogenarians also support the possibility that LpA-I might represent the anti-atherogenic fraction of HDL. Moreover, the concentration of LpA-I in children of parents with premature coronary heart disease was lower than that of a control group without any family history of this disease. Nutrients and hypolipidemic drugs seem to affect the two kinds of particles differently. PMID- 1597004 TI - Characterization of cryoglobulins by immunoblotting. AB - We adapted an immunoblotting technique for the immunochemical characterization of cryoglobulins. We first compared the results from 157 samples with results obtained by immunofixation and immunoelectrophoresis and then with clinical observations in 125 cases. Full identification was possible in 98% of the cases by immunoblotting, in 54% by immunofixation, and in 28% by immunoelectrophoresis. Novel microheterogeneity aspects were observed by immunoblotting and immunofixation in 13% and 6% of the cases studied, respectively. Our results confirm the frequency of autoimmune and infectious diseases associated with mixed cryoglobulinemias, whereas a lymphoproliferative syndrome was observed only in cases of cryoglobulinemia with a monoclonal constituent or a microheterogeneity aspect, which was not always revealed by immunofixation or immunoelectrophoresis. The pathophysiological importance and classification of microheterogeneity aspects is not clear. These observations justify using a sensitive and specific method for identifying cryoglobulins, even when present at low concentrations, and call for long-term studies of these patients. PMID- 1597005 TI - Measuring urinary glycosaminoglycans in the presence of protein: an improved screening procedure for mucopolysaccharidoses based on dimethylmethylene blue. AB - Earlier we described a simple and reliable screening procedure in urine for mucopolysaccharidoses based on the color reaction of glycosaminoglycans (GAGs) with dimethylmethylene blue. At physiological concentrations of urinary protein, we observed an obvious interference by protein in the assay. By modifying the assay, we abolished the protein interference. The modified procedure is not disturbed by human serum albumin, IgG (both tested with as much as 5 g/L of protein), or urinary proteins. The modified procedure appeared as reliable as the original. No false-negative results were found in a series of 26 urine samples from patients with mucopolysaccharidoses (sensitivity 100%). In a series of 405 urine samples offered for metabolic screening, 24 samples with increased GAG content and normal GAG composition were seen (specificity 94%). The method may also be applicable for determining GAG in other body fluids or solutions containing protein. PMID- 1597006 TI - Automated homogeneous liposome immunoassay systems for anticonvulsant drugs. AB - We developed automated homogeneous immunoassays, based on immunolysis of liposomes, for measuring phenytoin, phenobarbital, and carbamazepine from serum. Liposome lysis was detected spectrophotometrically from entrapped glucose-6 phosphate dehydrogenase activity. The procedure was fully automated on a routine automated clinical analyzer. Within-run, between-run, dilution, and recovery tests showed good accuracies and reproducibilities. Bilirubin, hemoglobin, triglycerides, and Intrafat did not affect assay results. The results obtained by liposome immunoassays for phenytoin, phenobarbital, and carbamazepine correlated well with those obtained by enzyme-multiplied immunoassay (Syva EMIT) kits (r = 0.995, 0.986, and 0.988, respectively) and fluorescence polarization immunoassay (Abbott TDx) kits (r = 0.990, 0.991, and 0.975, respectively). The proposed method should be useful for monitoring anticonvulsant drug concentrations in blood. PMID- 1597008 TI - Concentration dependencies of immunoturbidimetric dose-response curves: immunoturbidimetric titer and reactivity, and relevance to design of turbidimetric immunoassays. AB - To characterize polyclonal antisera for two-point immunoturbidimetric applications, we defined, as functions of antiserum concentration, two parameters derived from dose-response curves: the maximum bichromatic optical response, Tmax, and the antigen concentration in the region of excess antibody corresponding to one-half Tmax, or C50. We raised monospecific polyclonal antisera in goats against several human immunoglobulins, C-reactive protein, C3, C4, apolipoproteins A-I and B, and several other proteins. We could linearly relate the logarithm of the antiserum concentration to log C50 and to log Tmax. The concentration of polyethylene glycol affected not only C50 and Tmax but also their functional dependencies on antiserum concentration. We devised two definitions of immunoturbidimetric titer and related them to the titer obtained by the single radial immunodiffusion method of Becker (Immunochemistry 1969; 6:539-46). PMID- 1597007 TI - Effects of albumin and immunoglobulin A on fructosamine assay. AB - Serum fructosamine, albumin, and IgA were measured in three groups of human subjects: 54 nondiabetic normal individuals, 149 nondiabetic patients, and 149 diabetic patients. Normal subjects had significantly (P less than 0.05) higher fructosamine (2.91, SD 0.33, mmol/L) than did nondiabetic patients (2.49, SD 0.46, mmol/L). Each of these groups had significantly (P less than 0.05) lower fructosamine than did diabetic patients (3.76, SD 1.16, mmol/L). Increased fructosamine appeared to be associated with increases in both albumin and IgA. However, fructosamine was significantly (P less than 0.05) correlated with neither albumin nor IgA in the normal group, with only albumin in the nondiabetic group, but with both albumin and IgA in the diabetic group. Selective combinations of these populations not only shifted these significances but also eliminated some of the correlations. Our results suggest caution regarding the diagnostic role and universality of fructosamine and of its correlation with IgA as indicated by others. PMID- 1597009 TI - Urinary glycosaminoglycan excretion in rheumatic diseases. AB - We used Alcian Blue (AB) and dimethylmethylene blue (DMB) methods to measure glycosaminoglycan (GAG) excretion in the first morning urine specimens of patients with osteoarthritis (OA), ankylosing spondylitis (AS), and rheumatoid arthritis (RA) in different stages of disease. By the AB method, urinary GAG excretion in patients with RA was not different from healthy control subjects. However, the DMB method showed significant differences (in milligrams of GAG per gram of creatinine) for OA (median 25.4, range 14.3-44.0, P less than 0.01, n = 23) and RA patients (median 33.0; range 10.0-147.6; P less than 0.001, n = 63) in comparison with unaffected individuals (median 20.2; range 8.9-41.4, n = 38). We noted a significant difference in urinary GAG excretion between RA and OA patients (P less than 0.01) and between RA and AS (P less than 0.01) patients. The DMB method was further investigated by clinical decision analysis. The DMB method is simple and rapid and may be useful in diagnosing RA by distinguishing between RA and OA or AS. PMID- 1597010 TI - Radioimmunoassay of beta-endorphin in ventricular and lumbar cerebrospinal fluid. AB - We describe a sensitive beta-endorphin (beta-EP) radioimmunoassay specific for beta-EP 1-31 applied to human ventricular and lumbar cerebrospinal fluid (CSF). Specificity was documented by reversed-phase HPLC of CSF pools. Simultaneous ventricular and lumbar CSF samples from 13 patients suspected of having normal pressure hydrocephalus showed median beta-EP values of 2.2 (range 1.7-4.0) and 4.8 (2.8-14.6) pmol/L, respectively. Ventricular and lumbar beta-EP concentrations were positively correlated (Spearman r = 0.72, P = 0.013). The beta-EP rostral-caudal gradient was closely related to the CSF protein gradient. HPLC profiles of beta-EP immunoreactivity were similar in ventricular and lumbar CSF with both C- and N-terminal antisera. beta-EP concentrations did not vary in the first 12 mL of lumbar CSF, tapped in 3-mL portions [F(3,32) = 0.42, P = 0.74]. The beta-EP concentration in lumbar CSF from 15 children in remission from acute leukemia [23.4 (15.0-27.1) pmol/L] was higher than in 54 healthy adults [11.7 (10.9-13.3) pmol/L; P less than 0.01]. There was no effect of sex or age on CSF beta-EP in adults. beta-EP in lumbar human CSF may indicate di- and mesencephalic beta-EP neuronal activity. PMID- 1597011 TI - Preliminary treatment of urinary proteins improves electrophoretic analysis and immunodetection. AB - Analysis of urinary protein composition is an important tool in studies on renal physiology and physiopathology. Urine is, however, a complex mixture containing, besides protein, a variety of compounds such as salts, peptides, oligosaccharides, and glycosaminoglycans. Some of these compounds interfere with the electrophoretic migration of protein in sodium dodecyl sulfate-polyacrylamide gels and prevent correct analysis of the protein pattern. We describe a simple method for extracting urinary proteins that considerably improves their electrophoretic migration and subsequent immunodetection. This treatment involves ammonium sulfate fractionations (for precipitating proteins), EDTA (for inhibiting protein aggregation), and HCl hydrolysis (for removing glycosylaminoglycans). Recovery during extraction was found to be almost quantitative for total protein and three representative proteins: albumin, alpha 1-glycoprotein acid, and beta 2-microglobulin. PMID- 1597012 TI - Biological variability of lipoproteins and apolipoproteins in patients referred to a lipid clinic. AB - We determined the physiological variability of total cholesterol, high- (HDL) and low-density lipoprotein (LDL) cholesterol, triglycerides, and apolipoproteins A-I and B in fasting blood samples from patients referred to the Johns Hopkins Lipid Referral Clinic. Samples were taken on each of three occasions during baseline evaluation visits before the patients were treated. The median physiological coefficients of variation (CVp) were as follows: total cholesterol, 5.0%; triglycerides, 17.8%; HDL cholesterol, 7.1%; LDL cholesterol, calculated from the previous three measurements, 7.8%; and apolipoproteins A-I and B, 7.1% and 6.4%, respectively. There were no significant differences in CVp between children (less than or equal to 18 years) and adults (greater than 18 years) for any of the measurements. On the basis of our findings, single measurements in serial samples taken on three occasions suffice to establish the patients' usual values with the following precisions (+/- 1 CV): total cholesterol, +/- 4%; triglycerides, +/- 11%; HDL cholesterol, +/- 8%; LDL cholesterol, +/- 6%; and apolipoproteins A-I and B, +/- 7%. PMID- 1597013 TI - Improved electrochemiluminescent label for DNA probe assays: rapid quantitative assays of HIV-1 polymerase chain reaction products. AB - We describe the characterization and utility of a new electrochemiluminescent (ECL) label for oligonucleotides, utilizing phosphoramidite chemistry. This phosphoramidite of the tris(2,2-bipyridine)ruthenium(II) complex, bis(2,2 bipyridine)(4-[4-(2-cyanoethoxy-N,N-diisopropyl-amino) phosphinoxybutyl]4' methyl)2,2-bipyridine ruthenium(II) dihexafluorophosphate or Origen phosphoramidite, enables the direct incorporation of the label during automated DNA synthesis. Efficiency of this automated synthesis allows the direct utilization of probes without further purification. Introduction of this labeling group is reproducible, and the ECL signal recovered is not influenced by hybridization. Furthermore, neither hybridization kinetics nor hybrid stability was affected by our label. We also demonstrate the utility of these labels for the development of rapid assays with oligonucleotides direct from automated synthesis. The clinical utility of these labeled oligonucleotides is shown with assays of total nucleic acid, extracted from peripheral blood lymphocytes of patients with acquired immunodeficiency syndrome (AIDS), to detect the human immunodeficiency virus (HIV-1). The results demonstrate the ability of the assay to quantify 30-2000 copies of HIV1 gag genes and to rapidly detect (less than 45 min) HIV-1 gag genes in a nonseparation assay. The application of this assay to clinical samples demonstrates the utility of these assays for rapid and quantitative analysis. PMID- 1597015 TI - Intralaboratory performance requirements necessary to pass proficiency testing: CAP-1990 vs CLIA-1967 (March 14, 1990) formats compared. AB - The pre-1990 College of American Pathologists' (CAP) Proficiency Testing (PT) program used a two samples per analyte/four challenges per year format with performance or pass-fail grading criteria determined by the program. On Jan. 1, 1991, the Clinical Laboratory Improvement Act of 1967 (CLIA-67) final rules (March 14, 1990) mandated a revised PT format of five samples per analyte/four challenges per year, with the regulations specifying minimum performance criteria. Extending our previous analysis, we compare the maximum permissible intralaboratory imprecision at low bias compatible with passing external PT in the former CAP and current CLIA-67 formats. If a laboratory is able to reduce its internal coefficient of variation (CV) to less than 44% of the PT criterion for each analyte, its overall chance of adverse action for any of the 27 routine chemistry analytes specified in CLIA-67 will be less than 1% in a two-year (eight PT challenges or events) period. Consideration of actual interlaboratory CVs from CAP surveys suggest that a reduction of this magnitude may be difficult for the analytes total cholesterol and blood urea nitrogen, where intralaboratory imprecision comparable with the group standard deviation (SD) from 1990 CAP surveys would yield individual adverse action (PT failure) rates of 5% and 1%, respectively. Five other analytes have CLIA-67 performance limits dangerously close to CAP interlaboratory CVs. PMID- 1597014 TI - Is free thyroxine accurately measurable at room temperature? AB - Two recently developed two-step, or "back-titration" assay kits for free thyroxine (FT4)--one based on a europium-labeled derivative of T4, the other on conventional radiolabeled T4--were compared with both symmetrical dialysis and an indirect FT4 radioimmunoassay. Discrepancies between the two-step and the other two methods were observed, particularly in samples that had very low to zero thyroxine-binding globulin (TBG) content. In those instances the two-step methods gave values almost twice as high as the other methods. This effect could be largely reversed in one of the two-step assays and completely reversed in the other by performing the first incubation step at 37 degrees C rather than at room temperature, as prescribed by the manufacturers. When symmetrical dialysis is performed at both temperatures, FT4 at room temperature is about 40% of the amount determined at 37 degrees C, except in zero-TBG samples, where it averages almost 80% of the value at 37 degrees C. Moreover, we demonstrated that the affinity of TBG for T4 is much more temperature-dependent than the affinity of transthyretin and albumin for T4, so that the net temperature effect on the FT4 in a sample depends on the relative contribution of TBG to total binding. We conclude that performing FT4 assays at room temperature is principally incorrect and leads to falsely increased values when samples with very low TBG concentrations are analyzed. PMID- 1597016 TI - Single stable reagent (Arsenazo III) for optically robust measurement of calcium in serum and plasma. AB - We describe a method based on a single stable reagent for the determination of calcium in serum and plasma with use of Arsenazo III, 200 mumol/L in 50 mmol/L 1,4-piperazinediethanesulfonic acid (PIPES) buffer. The method showed significant positive interference in plasma at pH less than 6.6 because of the precipitation of fibrinogen, which was eliminated by increasing the pH to 6.8. The assay showed no interference from as much as 600 mumol of bilirubin and 12 g of hemoglobin per liter when applied in a simple monochromatic procedure at 660 nm. The standard curve for calcium was linear from 0 to 5.0 mmol/L. Addition of Intralipid at concentrations greater than 3 g/L demonstrated positive interference, which could be eliminated by using a 700-nm blanking wavelength. The procedure showed good agreement with all-method mean values from two external quality-control schemes. PMID- 1597017 TI - A study of experimental lancets for blood collection to avoid bone infection of infants. AB - We describe a study made at two pediatric centers to test experimental lancets for blood collection by skin puncture of infants' heels or fingers. Our primary goal is to decrease the hazard of osseous injury while collecting adequate blood, by using three lancet widths at a constant length of 1.0 mm. The three widths used were 1.0, 1.25, and 1.5 mm. When success at skin puncture was defined rigidly on the basis of the blood volume obtained, the data show that success was related neither to the lancets' dimensions as tested nor to the age of the child, but rather to the phlebotomist's skill and experience, which improved with time. PMID- 1597018 TI - American Association for Clinical Chemistry, Inc., 44th national meeting. July 19 23, 1992, Chicago, IL. Abstracts. PMID- 1597019 TI - A tribute to Frank H. Netter, MD 1906-1991. PMID- 1597020 TI - Clinical trials of immunotherapy for sepsis. PMID- 1597021 TI - Definitions for sepsis and organ failure. PMID- 1597022 TI - A tale of two intensive care units? All intensive care units are not the same! PMID- 1597023 TI - Observations using antiendotoxin antibody (E5) as adjuvant therapy in humans with suspected, serious, gram-negative sepsis. AB - OBJECTIVE: To evaluate the safety and efficacy of E5 (Xomen-E5), a murine monoclonal immunoglobulin M antibody, in reducing mortality in patients with serious Gram-negative infections. Phase II, single-site study. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Surgical, neurosurgical and medical ICUs, comprising approximately 30 beds in a multidisciplinary university hospital. PATIENTS: Patients with clinical evidence of serious infection admitted to the ICU for monitoring of vital signs and for intensive care nursing. Of the 39 patients enrolled in the study, 23 had documented Gram-negative infection. METHODS: Patients suspected of having life threatening Gram-negative infections received one of two doses of E5 or placebo. Safety and efficacy were assessed by survival on days 3, 7, and 21, appearance of adverse reactions, development of antimurine antibodies, and effects on BP, urine output, WBC count, and temperature. MEASUREMENTS AND MAIN RESULTS: Mortality rate from Gram-negative infection 3 days after the last drug (or placebo) infusion was two (22%) of nine deaths in the placebo group compared with 0 of nine for E5 2.5 mg/kg and 0 of five for E5 7.5 mg/kg. At 21 days after therapy, three patients treated with E5 had died. Only one of these three deaths resulted from infection. Eight of 15 E5 patients tested had immunoglobulin G antimurine antibodies by 3 wks after therapy began, but all were asymptomatic. CONCLUSIONS: E5 was well tolerated and may have the potential to reduce early morbidity and the mortality rate in seriously ill patients with Gram-negative infections. Results from larger phase III studies are needed to confirm these findings. PMID- 1597024 TI - Reversal of midazolam sedation with flumazenil. AB - OBJECTIVE: To demonstrate the efficacy of flumazenil in reversing the sedative action of midazolam in ventilated intensive care patients. DESIGN: Prospective, double-blind randomized study. SETTING: ICU of a tertiary, university-affiliated teaching hospital. PATIENTS: Thirty ICU patients requiring artificial ventilation for greater than 12 hrs were studied. INTERVENTIONS: All patients received a midazolam infusion for sedation. Twenty-nine patients received supplementary narcotics. At the end of the sedation period, either flumazenil or placebo was administered to all the patients in a double-blind, randomized fashion, and the effects were observed. MEASUREMENTS AND MAIN RESULTS: Sedation levels were measured hourly during the infusion; at the end of the infusion; and at 5, 15, 30, 60, and 120 mins after cessation of the midazolam infusion. Midazolam concentrations in serum were measured at the time of cessation of the midazolam infusion and at 30, 60, and 120 mins later. Reversal of sedation was observed in 14 of 15 patients who received flumazenil, and resedation occurred in seven of these patients. Reversal was not seen in any of the patients who received placebo. Midazolam serum concentrations were similar in both groups. CONCLUSION: Flumazenil in a dose of 0.15 mg is a safe drug that reverses the sedative effect of midazolam. PMID- 1597025 TI - Colonization of dental plaque by respiratory pathogens in medical intensive care patients. AB - OBJECTIVE: To assess the prevalence of oral colonization by respiratory pathogens in a group of ICU patients, with specific attention to dental plaque and the oral mucosa. DESIGN: Prospective, nonrandomized study with age-matched controls. SETTINGS: Medical ICU in a tertiary-care Veterans Affairs Medical Center and a dental school outpatient preventive dentistry clinic. PATIENTS: Nonconsecutive, unselected patients admitted to the medical ICU during a 2-month period; controls were age-matched patients seen for the first time in the preventive dentistry clinic. INTERVENTIONS: None. MEASUREMENTS: Oral hygienic status was assessed in both groups using a semiquantitative system. Quantitative cultures of dental plaque and buccal mucosa were done within 12 hrs of medical ICU admission and every third day thereafter until discharge/death from the medical ICU. In controls, cultures of plaque and buccal mucosa were done on the initial visit only. Severity of illness of medical ICU patients was quantitated using the Acute Physiology and Chronic Health Evaluation (APACHE II) system and McCabe-Jackson criteria. MAIN RESULTS: Oral hygiene of medical ICU patients was poor. These patients had a mean plaque score (1.9 +/- 0.2) that was significantly greater than that same score seen in outpatients of the preventive dentistry clinic (1.4 +/- 0.1; p less than .005). Plaque and/or oral mucosa of 22 (65%) of 34 medical ICU patients were colonized by respiratory pathogens, in contrast to only four (16%) of 25 preventive dentistry clinic patients (p less than .005). The potential respiratory pathogens cultured from medical ICU patients included methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, and ten genera of Gram-negative bacilli. Colonization by respiratory pathogens was statistically associated with concomitant antibiotic therapy within the medical ICU group of patients, but not with severity of illness. Although medical ICU patients tended to have more dental plaque than preventive dentistry clinic patients, there was no statistically significant association noted between the presence of dental plaque and respiratory pathogen colonization. CONCLUSIONS: These findings suggest that bacteria commonly causing nosocomial pneumonia colonize the dental plaque and oral mucosa of intensive care patients. In many cases, this colonization occurs by large numbers of bacteria. Dental plaque may be an important reservoir of these pathogens in medical ICU patients. Efforts to improve oral hygiene in medical ICU patients could reduce plaque load and possibly reduce oropharyngeal colonization. PMID- 1597026 TI - Septic shock in patients with cirrhosis: hemodynamic and metabolic characteristics and intensive care unit outcome. AB - OBJECTIVES: To examine the hemodynamic and metabolic characteristics and ICU outcome of septic shock in patients with cirrhosis. DESIGN: Prospective, comparative study. Measurements performed in the first 24 hrs of septic shock. SETTING: A general hospital ICU. PATIENTS: Twelve patients with cirrhosis and 23 patients without cirrhosis admitted for septic shock. MEASUREMENTS AND MAIN RESULTS: Arterial pressure was measured using an arterial catheter. Pulmonary arterial and right atrial pressures were measured by using a pulmonary artery catheter. Cardiac output was determined by using the thermodilution method. Pulmonary arterial L-lactate plasma concentrations were measured using an automated spectrophotometer, and blood temperature was measured using a cardiac output computer. Arterial and mixed venous PO2, PCO2, and pH values were measured by using specific electrodes. Oxygen saturations and hemoglobin concentrations were measured using a hemoximeter. Patients with cirrhosis had decompensated liver disease (grade C of the Child-Pugh classification). The number of Gram negative infections and therapeutic interventions were similar in both groups. Patients with cirrhosis had higher cardiac indices (5.14 +/- 0.52 [SE] vs. 3.91 +/- 0.30 L/min/m2, p less than .05), plasma lactate concentrations (9.0 +/- 2.0 vs. 5.2 +/- 0.7 mmol/L, p less than .05) and ICU mortality rates (100% vs. 43%, p less than .05), and lower blood temperatures (35.5 +/- 0.6 vs. 37.6 +/- 0.2 degrees C, p less than .05) than patients without cirrhosis. Systemic vascular resistance, arterial pressure, pulmonary arterial pressure, oxygen delivery and consumption, and arterial and mixed venous acid-base status were not significantly different between the two groups. CONCLUSIONS: In patients with cirrhosis, septic shock was characterized by severe liver dysfunction, low blood temperature, marked increases in cardiac index and lactic acidemia, and a 100% ICU mortality rate. These findings should be taken into account if patients with cirrhosis are to be included in controlled studies on septic shock. PMID- 1597028 TI - Outcome of intensive care of the "oldest-old" critically ill patients. AB - OBJECTIVE: To determine the short-term and long-term outcome of critically ill "oldest-old" (greater than or equal to 85 yrs) patients. DESIGN: Retrospective chart review and follow-up telephone interview. SETTING: ICUs at a tertiary care hospital. METHODS: The medical records of all patients greater than or equal to 85 yrs of age admitted to the ICUs during 1988 were reviewed. Demographic information, severity of illness, major interventions, mortality rate, and hospital charges were examined. A follow-up telephone interview was conducted to determine the quality of life and mortality rate after discharge. RESULTS: Of 34 patients greater than or equal to 85 yrs of age admitted to the ICU, 21 (62%) survived to discharge from the hospital, and 13 (62%) of these 21 patients were discharged to home. Mean +/- SD hospital charges were $34,738 +/- 34,366. Seventeen of the 21 patients were contacted for long-term follow-up, and ten of these patients were alive at a mean follow-up time of 18 +/- 10 months (range 1 to 32). Eight of the ten patients described their quality of life as fair or good. CONCLUSION: These findings suggest that age alone may be an inappropriate criterion for allocation of ICU resources. PMID- 1597027 TI - Lung mechanics during and after extracorporeal membrane oxygenation for meconium aspiration syndrome. AB - OBJECTIVE: To determine whether abnormalities in lung mechanics detected in infants during the acute phase of meconium aspiration syndrome persist after treatment with extracorporeal membrane oxygenation (EMCO). DESIGN: Prospective, descriptive study. Prospective evaluation of airway function and lung mechanics during and after ECMO by pulmonary function testing at 1.8 +/- 0.5 days of EMCO (period 1), follow-up at 1.4 +/- 0.2 days (period 2), and 7.0 +/- 0.9 days (period 3) after decannulation from ECMO. SETTING: Tertiary care neonatal/pediatric ICU. PATIENTS: Twelve neonates undergoing ECMO treatment for severe meconium aspiration syndrome that was refractory to conventional mechanical ventilation. INTERVENTIONS: Maximum expiratory flow-volume curves were studied with the deflation flow-volume curve technique, and compliance and resistance of the respiratory system were studied with partial passive flow volume curves. MEASUREMENTS AND MAIN RESULTS: Respiratory system compliance was the only index of respiratory mechanics that was significantly (p less than .05) improved (0.96 +/- 0.1 vs. 0.61 +/- 0.1 mL/cm H2O/kg) immediately after decannulation from ECMO compared with period 1. Clinically important (p less than .05) improvement in forced vital capacity (28.0 +/- 5.5 vs. 16.1 +/- 1.9 mL/kg), respiratory system compliance (1.01 +/- 0.2 vs. 0.61 +/- 0.1 mL/cm H2O/kg), and maximum expiratory flow at 25%/forced vital capacity (1.0 +/- 0.3 vs. 2.2 +/- 0.3) was evident only during period 3 compared with period 1. CONCLUSIONS: We conclude that improvements in the clinical condition and oxygenation, permitting successful decannulation from ECMO, are achieved before clinically important improvements in lung mechanics. PMID- 1597029 TI - Do older internists use more hospital resources than younger internists for patients hospitalized with chest pain? A study of patients hospitalized in the coronary care and intermediate care units. AB - OBJECTIVES: Recent concern about escalating healthcare expenditures has prompted healthcare payers and hospitals to identify physicians whose hospital resource consumption exceeds expected norms. The goals of this study were to determine whether analyses of practice patterns in this manner may a) systematically identify older physicians as big resource "spenders," and b) provide misleading information caused by the failure to adjust utilization data for severity of illness. DESIGN: A prospective, observational study. SETTING: The coronary care and intermediate care unit in an 1,100-bed community hospital. PATIENTS: A total of 217 patients hospitalized for chest pain cared for by noncardiologists. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: On initial inspection, it appeared that the patients of older physicians had longer lengths of stay and greater charge expenditures than the patients of younger physicians. However, further evaluation demonstrated that older physicians cared for older (76 vs. 67 yrs old, p = .0001) and more severely ill patients (judged by risk of complications, risk of acute ischemic heart disease, and disease staging). Older physicians cared for more severely ill myocardial infarction patients than did younger physicians (Killip Classification 2.0 vs. 1.1, p less than .00003). After adjusting for severity of illness, there were fewer differences in hospital charges and consultant use between older and younger physicians, although the patients of older physicians remained hospitalized longer. CONCLUSIONS: There is little difference in resource utilization between patients cared for by older and younger internists after controlling for severity of illness. This investigation highlights the potential hazards of ignoring severity of illness when judging physician efficiency in the coronary care unit. PMID- 1597030 TI - Indirect calorimetry in mechanically ventilated infants and children: measurement accuracy with absence of audible airleak. AB - OBJECTIVE: To establish the effect of an audible airleak (around an endotracheal tube) on oxygen consumption (VO2) measurements in pediatric ICU patients. DESIGN: Prospective trial comparing VO2 measurements before and after deflation of the endotracheal tube cuff. SETTING: Pediatric ICU in a large pediatric tertiary care center. PATIENTS: Twenty critically ill infants and children receiving mechanical ventilatory support via cuffed endotracheal tube. INTERVENTIONS: Deflation of endotracheal tube cuff. MEASUREMENTS AND MAIN RESULTS: The presence (group 1, n = 9) or absence (group 2, n = 11) of an audible airleak with the cuff deflated was confirmed by two independent observers. The percent difference in VO2 was calculated for both groups using the following formula: ([VO2 cuff up - VO2 cuff down]/VO2 cuff up) x 100. An audible airleak associated with cuff deflation (group 1) caused a significant (p = .0012) reduction of VO2 by 45.6% (mean difference in VO2 = 45.6%). In contrast, with no audible airleak after cuff deflation (group 2), only minimal changes in VO2 (mean difference in VO2 = -0.4%) were observed. CONCLUSIONS: These data suggest that if no audible airleak is detected, VO2 determined by indirect calorimetry may be reliably measured in infants and children with a noncuffed endotracheal tube. PMID- 1597031 TI - Cerebral blood flow pattern and autoregulation during open-heart surgery in infants and young children: a transcranial, Doppler ultrasound study. AB - OBJECTIVES: To elucidate the effect of cardiopulmonary bypass on cerebral perfusion and on the autoregulatory ability of the cerebral vascular bed of infants and young children. SETTING: Operating room. DESIGN: Prospective study. PATIENTS: Thirteen newborn infants and young children undergoing open-heart surgery. INTERVENTIONS: Cerebral blood flow velocity was monitored in the patients undergoing open-heart surgery from just before the induction of anesthesia until the discontinuation of anesthesia after completion of the surgery. MEASUREMENTS AND MAIN RESULTS: Cerebral blood flow velocity was assessed by semicontinuous measurement of temporal mean blood flow velocity in the middle cerebral artery using a range-gated, pulsed Doppler flowmeter with a transducer that was firmly attached to the left temporal region of the head. Mean arterial pressure (MAP) and nasopharyngeal temperature were continuously monitored. During hypothermic (18.4 degrees C to 31.9 degrees C) cardiopulmonary bypass, cerebral blood flow velocity decreased and showed a close relationship with nasopharyngeal temperature (p less than .0001). During steady-state cardiopulmonary bypass, cerebral blood flow velocity showed a correlation with MAP (p less than .01). The nasopharyngeal temperature influenced this relationship: at lower (absolute) nasopharyngeal temperatures, lack of cerebral autoregulation was more common. CONCLUSIONS: The finding suggests that cerebral blood flow decreases with decreasing nasopharyngeal temperature. During hypothermic cardiopulmonary bypass, cerebral autoregulation seems to be easily disturbed, especially at low nasopharyngeal temperatures. PMID- 1597032 TI - Lack of relationship between the true airway pressure and the pressure displayed with an infant ventilator. AB - OBJECTIVE: To establish if the pressure indicated in the manometer of an infant ventilator (IV 100B, Sechrist, Anaheim, CA) reflects the true pressure delivered to the proximal airway during mechanical ventilation in the neonatal ICU. DESIGN: With approval of our Institutional Research Board, data were collected prospectively. Peak inspiratory pressure and end-expiratory pressure were measured at the "Y" piece of the breathing tubing. Pressure readings from the conventional ventilator's manometer were compared with simultaneously obtained measurements using an electronic monitor. SETTING: This study was conducted in a 45-bed neonatal ICU, admitting 700 to 750 newborns per year. PATIENTS: Twelve neonates who required mechanical ventilation were included in the study. INTERVENTIONS: Specific interventions were not made by study design. Measurements routinely obtained were compared. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-five simultaneous measurements of peak inspiratory pressure and positive end-expiratory pressure were compared. Peak inspiratory pressure values were higher with the electronic monitor in 273 (99%) of 275 measurements and the mean of the differences between the electronic monitor and ventilator's manometer was statistically significant (p less than .001). For positive end-expiratory pressure measurements, values indicated by the electronic monitor were lower in 152 (55%) of 275 determinations, equal in 65 (23%), and higher in 58 (21%) determinations. Percent variations between methods ranged from 0% to 140% for peak inspiratory pressures and from 0% to 500% for positive end-expiratory pressure. CONCLUSIONS: These data demonstrate that it is impossible to know the true pressure delivered to the proximal airway of a neonate during mechanical ventilation by observing the ventilator pressure manometer. The manometer readings consistently underestimate the true peak inspiratory pressure values and are very unpredictable regarding positive end-expiratory pressure values. These findings support the use of other methods to monitor the proximal airway pressure besides the ventilator's manometer in the neonatal ICU. Furthermore, mean airway pressure should not be calculated from the pressure readings obtained from the tested ventilator's manometer. PMID- 1597033 TI - Relationship between hepatic blood flow and tissue lipid peroxidation in the early postburn period. AB - OBJECTIVES: To determine the effect of a body burn on effective or nutrient liver blood flow and the relationship between blood flow and oxidant-induced lipid peroxidation. DESIGN: Anesthetized sheep were given a 40% of total body surface, third-degree burn, after which animals were fluid resuscitated to return ventricular filling pressures and cardiac output to baseline values. Animals, for the 6-hr study period, were resuscitated with lactated Ringer's solution alone or lactated Ringer's solution plus 1500 mL of 5% hydroxyethyl starch or lactated Ringer's solution plus hydroxyethyl starch on which was complexed the iron chelator deferoxamine to prevent oxidant release. Effective liver blood flow was measured using the galactose infusion technique. Liver tissue lipid peroxidation was monitored using malondialdehyde content. RESULTS: We found that effective liver blood flow was decreased by 50% in the 4- to 5-hr postburn period, even when animals were resuscitated to baseline cardiac output values with lactated Ringer's solution. Tissue malondialdehyde content increased in the group treated with lactated Ringer's solution from a control value of 110 +/- 7 to 202 +/- 59 nmol/g of tissue. Resuscitation with hydroxyethyl starch restored postburn effective liver blood flow to control values, but malondialdehyde content was still increased two-fold. Resuscitation with hydroxyethyl starch and deferoxamine resulted in an increase in effective liver blood flow postburn to a value 80% above controls. In addition, lipid peroxidation was prevented. CONCLUSIONS: Effective liver blood flow is markedly decreased after burn injury, even with apparently adequate volume resuscitation, when using lactated Ringer's solution. Liver lipid peroxidation persists even when effective liver blood flow is maintained, indicating that the oxidant process is not solely related to blood flow. Infusion of the antioxidant deferoxamine during resuscitation not only prevents the lipid peroxidation, most likely by a nonblood-flow-related process, but also results in an increase in blood flow above normal rates, suggesting that postburn liver oxygen needs exceed normal values. PMID- 1597034 TI - Evaluation of strategies for central venous catheter replacement. AB - OBJECTIVES: To assess the consequences of leaving a bacterially colonized central venous catheter in place and to compare the effects of three catheter replacement strategies for catheter repair control in an animal model. DESIGN: Prospective study. SETTING: Laboratory and animal facility of a large university. SUBJECTS: Eighteen healthy, female, adult sheep. INTERVENTIONS: Radiopaque-siliconized elastomer central venous catheters were inserted into the jugular veins and colonized with either Escherichia coli or Staphylococcus epidermidis. After 7 days of infection, the catheters were either: a) exchanged using a guidewire; b) removed and replaced with a new catheter in a new jugular vein site after a 48-hr interval; or c) exchanged using a guidewire and antibiotics (tobramycin, cephaloridine) injected into the catheter. Animals were euthanized 7 days after insertion of the new catheter. Quantitative microbiology was performed on blood samples collected daily from the catheters and a peripheral vein, as well as from catheters and tissue recovered from the sheep at the time of autopsy. MEASUREMENTS AND MAIN RESULT: When catheters were changed using a guidewire, they became colonized by bacteria within 48 hrs, and the sheep had embolic pneumonia and vegetative endocarditis at autopsy. Similar consequences were observed when antibiotics were administered into the catheter lumen. If colonized catheters were removed and a new catheter was inserted after a 48-hr interval, recolonization, pneumonia, and endocarditis were not observed. CONCLUSIONS: Replacement of a biofilm-colonized central venous catheter over a guidewire is associated with rapid colonization of the replacement catheter and production of detached, slime-enclosed, antibiotic-resistant aggregates that colonize other catheters or initiate endocarditis or pneumonia by dissemination in the bloodstream. PMID- 1597035 TI - Femoral arteriovenous extracorporeal carbon dioxide elimination using low blood flow. AB - BACKGROUND AND METHODS: Conventional extracorporeal CO2 removal systems require blood flow rates of 1 to 2.5 L/min in the extracorporeal circuit. We hypothesized that standard hemofiltration equipment can be combined with a high-performance extracorporeal lung to achieve high rates of CO2 removal at lower blood flow rates. To test this hypothesis, we performed experiments on nine sheep to examine the extent to which CO2 elimination can be achieved at blood flow rates less than 600 mL/min using a 5-m2 hollow fiber membrane lung with countercurrent gas flow, combined with a hemofiltration blood pump, and connected to femoral arterial and venous hemodialysis catheters. RESULTS: CO2 eliminations of 130 to 180 mL/min at standard temperature and pressure were achieved with blood flow rates in the range 470 to 600 mL/min. With a pumpless artery-to-vein shunt, up to 90 mL/min of CO2 at standard temperature and pressure was eliminated. However, in this mode, the resistance of the access catheters and tubing was the main factor limiting CO2 elimination. CONCLUSIONS: Standard hemofiltration equipment may be combined with a hollow fiber membrane lung to remove the equivalent of a high proportion of the basal metabolic CO2 production of an adult human at low blood flow rates. Use of this technology would bring extracorporeal CO2 removal within the budget and capability of more ICUs. PMID- 1597036 TI - Effect of experimental hemorrhagic shock on hepatic drug elimination. AB - OBJECTIVE: Exogenous substrates were used to measure hepatic function for the purposes of determining organ dysfunction and to evaluate the effect of experimental hemorrhagic shock with resuscitation on hepatic drug elimination. DESIGN: Prospective, controlled, non-randomized crossover trial. INTERVENTIONS: Eleven chronically instrumented immature swine were studied using a fixed-volume hemorrhage model (45 mL/kg blood removal over 15 mins) followed by resuscitation with lactated Ringer's solution at three times the volume of shed blood. One week before and immediately after hemorrhage and resuscitation, hepatic function markers (indocyanine green and antipyrine) were simultaneously administered intravenously. MEASUREMENTS: Physiologic data and blood samples were collected over 12 hrs after drug administration. Drug clearances, volumes of distribution, and half-lives were determined. MAIN RESULTS: For indocyanine green, there was no substantial change in pharmacokinetics from preshock to postshock, suggesting minimal change in hepatic blood flow. For antipyrine, clearance was decreased by 30% after shock and resuscitation (p = .05), suggesting that oxidative metabolism was acutely impaired. CONCLUSIONS: The information indicates that hepatic oxidative drug metabolism may be impaired early after hemorrhagic shock and that dosages of drugs in this class should be carefully examined when administered to patients who have sustained injury with hemorrhagic shock. PMID- 1597037 TI - Effect of a human immunoglobulin preparation for intravenous use in a rabbit model of meningococcal endotoxin-induced shock. AB - BACKGROUND AND METHODS: Endotoxin shock is mediated by various cytokines, including tumor necrosis factor. Treatment of patients with i.v. immunoglobulin has been shown to reduce the concentration of circulating cytokines. The purpose of this study was to determine the protective effects of immunoglobulin for i.v. use on meningococcal endotoxin-induced shock in a rabbit model. Experimental animals were challenged with i.v. meningococcal endotoxin (lipo-oligosaccharide) 10 micrograms/kg, and treated with either a 2-hr i.v. immunoglobulin infusion (400 mg/kg) or a similar saline infusion that was initiated 30 mins before endotoxin challenge. Control animals were challenged with saline alone. RESULTS: Compared with untreated control animals, pulse rate increased (p less than .007) and mean arterial pressure and serum bicarbonate concentrations decreased (p less than .02) in both experimental groups, but did not differ between immunoglobulin treated and saline-treated animals (p greater than .05) at any time after the endotoxin challenge. Geometric mean serum endotoxin concentrations were significantly (p less than .03) lower in the immunoglobulin-treated animals at 60, 120, 180, 240, 300, and 360 mins after the endotoxin challenge. The geometric mean serum tumor necrosis factor level at 1 hr after the endotoxin challenge in the immunoglobulin-treated experimental animals was lower than in saline-treated animals (5.53 vs. 8.47 tumor necrosis factor enzyme-linked immunosorbent assay U/mL), but not significantly so (p greater than .05). Mortality rate was similar in both experimental groups; eight (67%) of 12 saline-treated experimental rabbits and seven (70%) of ten immunoglobulin-treated rabbits died. All untreated control animals survived 24 hrs. CONCLUSIONS: In this model of circulatory shock in rabbits, i.v. immunoglobulin: a) does not significantly alter the physiologic responses to endotoxin challenge; b) significantly reduces endotoxin concentrations; c) reduces tumor necrosis factor concentrations, but not significantly; and d) does not improve survival rate. PMID- 1597038 TI - Dimethylthiourea ameliorates acute lung injury induced by phorbol myristate acetate in dogs. AB - BACKGROUND AND METHODS: The protective effects of dimethylthiourea, a potent scavenger of hydroxy radical (.OH) and hydrogen peroxide, in experimental lung injury in large animals remain controversial. The present study was designed to determine whether dimethylthiourea can ameliorate the acute lung injury produced in dogs by phorbol myristate acetate. Six dogs were infused with dimethylthiourea (0.75 g/kg in saline) for 1.5 hrs, beginning 1 hr before an i.v. bolus injection of phorbol myristate acetate (17 micrograms/kg); six dogs received phorbol myristate acetate (17 micrograms/kg) alone; and six dogs were infused with saline alone. Hemodynamic changes, arterial oxygenation, and the development of lung edema were monitored for 4 hrs after phorbol myristate acetate injection to assess the extent of lung damage. RESULTS: As compared with the dogs that received phorbol myristate acetate alone, the edematous lung damage was significantly reduced in those dogs that received dimethylthiourea as well as phorbol myristate acetate. In the dimethylthiourea-treated dogs, the lung wet/dry weight ratios were smaller (p less than .01); protein concentrations in lung lavage fluid were lower (p less than .01); the decrease in PaO2 was significantly reduced (p less than .01); and there were significant reductions in the alveolar arterial oxygen tension difference (P[A-a]O2) (p less than .01) and shunt (Qsp/Qt) (p less than .05). Also, dimethylthiourea significantly lowered the increased mean pulmonary arterial pressure levels during the second half of the experiment. CONCLUSIONS: These experimental data suggest that dimethylthiourea is capable of reducing the neutrophil-mediated lung injury produced by the release of hydroxy radical and/or hydrogen peroxide in dogs exposed to phorbol myristate acetate. PMID- 1597039 TI - Relationship between oxygen delivery and metabolic acidosis during sepsis in piglets. AB - OBJECTIVE: To determine if the preservation of oxygen delivery (DO2) ameliorates the development of metabolic acidosis during group B streptococcal infusion. METHODS: We examined 22 piglets (2 to 4 wks of age) that were anesthetized, intubated, and mechanically ventilated. Three groups of piglets were studied: group 1 (n = 6), in which DO2 was reduced progressively over 4 hrs by infusion of group B streptococci; group 2 piglets (n = 6) received a similar infusion of streptococci, but DO2 was preserved at presepsis levels by the infusion of dextran and exogenous porcine RBCs; group 3 piglets (n = 6) received no bacteria, but did receive a continuous infusion of 0.9% sodium chloride to maintain cardiac output, and thus, DO2, at baseline levels. To correlate arterial lactate concentrations with metabolic acidosis, four additional piglets received the continuous infusion of streptococci. RESULTS: DO2 decreased significantly in group 1 (14.2 to 5.7 mL oxygen/kg/min) but not in either group 2 or 3. The arterial pH decreased significantly in both septic groups, groups 1 and 2 (7.47 to 7.20; 7.45 to 7.36, respectively), but not in the uninfected group 3. The pH was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Base excess decreased significantly for group 1 and group 2 piglets (+1.5 to -13.9; -0.1 to -5.8 mM/L, respectively) but not in group 3. Base excess was significantly lower for group 1 vs. group 2 piglets at 210 and 240 mins of streptococcal infusion. Oxygen extraction increased significantly for only the low DO2 group 1 piglets (32% to 73%), and did not differ comparing group 2 vs. group 3. In both groups of septic piglets, metabolic acidosis developed before any detectable reduction in oxygen consumption. The increase in circulating lactate concentration (1.0 to 4.6 mM/L) was correlated with the decrease in base excess (-1.0 to -9.7 mM/L) in the four additional piglets that received an infusion of streptococci. CONCLUSIONS: Maintaining DO2 at presepsis levels ameliorated the development of metabolic acidosis during streptococcal infusion. Nevertheless, a significant degree of metabolic acidosis developed despite the preservation of DO2. PMID- 1597040 TI - Total electrical power failure in a cardiothoracic intensive care unit. AB - OBJECTIVE: To describe the management of patients in an ICU during failure of both primary and backup electrical systems, resulting in nonfunctioning monitors, mechanical ventilators, and other life-support equipment. DESIGN: Case report of power outage and discussion. SETTING: A 45-bed cardiothoracic surgical ICU in a tertiary-care teaching hospital. PATIENTS: Postoperative cardiothoracic surgical patients receiving i.v. infusions of vasoactive medications and mechanical ventilatory support. MAIN RESULTS: Support measures included the use of pneumatically powered mechanical ventilators, battery-operated transport monitors and infusion pumps, and recruitment of non-ICU personnel to assist with manual ventilation and patient care. Problems identified included communication difficulties caused by failure of electronic telephones, and physical access limitation due to failure of electrical door openers and security locks. CONCLUSIONS: Total electrical power failure can occur even when an emergency power system is in place. Although the occurrence of such failure is unlikely, provisions must be made for its occurrence in order to avoid catastrophic patient injury. Such provisions include a mental plan of action, provision of emergency support equipment, physical plant changes, and the provision of power-independent communication systems. Power demands and battery backup capability of equipment should be considered in future equipment purchases. The ICU staff should be aware of the structure and operation of backup electrical power sources. PMID- 1597041 TI - Descriptive analysis of critical care units in the United States. AB - OBJECTIVE: To gather data about available technology, staffing, administrative policies, and bed capacities of ICUs in the United States. DESIGN AND SETTING: On January 15, 1991, survey instruments were mailed to the administrators of 4,233 hospitals to gather information from the medical director of the institutions' respective ICUs for the purpose of developing a database on ICUs in the United States. The sampling frame for this study was based on all American Hospital Association (AHA) hospitals that stated they have ICUs. MEASUREMENTS: Census questionnaires solicited information on types of hospitals, types of ICUs, number of ICU beds open and closed, technology available to the unit, organizational structure and management of the ICU, as well as the staffing and certification of unit personnel. MAIN RESULTS: Data were obtained on 32,850 ICU beds with 25,871 patients from 2,876 separate ICUs in 1,706 hospitals in the United States. Census responses came from units in all sizes of hospitals within all ten census regions in the country, all states, and all types of hospital sponsorship (federal, state, and local government, private nonprofit and private for profit). The census response rate was 40% of the AHA hospitals that stated that they have ICUs, with specific ICU data on 38.7% of the nation's ICUs. The number of ICUs per hospital increases with overall hospital size. The smallest hospitals (less than 100 beds) usually had only one ICU. As hospital size increased, the single, all inclusive medical/surgical/coronary care units diminished, and in hospitals with greater than 300 beds, specialization of units became prevalent. In absolute terms, hospitals had the following number of ICUs: 1.04 +/- 0.20 (less than or equal to 100 beds); 1.30 +/- 0.65 (101 to 300 beds); 2.37 +/- 1.58 (301 to 500 beds); and 3.34 +/- 2.21 (greater than 500 beds). ICU beds averaged, nationally, 8.09% of hospital-licensed beds with a median of 6.98%. Generally, medical units, pediatric units, coronary care units (CCUs), and medical/surgical/CCUs reported an average of 10 beds per unit. Neonatal units averaged 21 beds, and surgical units averaged 12 beds. The average ICU size, nationally, was 11.7 +/- 7.8 beds per unit. Available technology within hospitals and individual units was increased as hospital size increased; surgical units tended to have more available technology than other unit types. A wide range of organizational arrangements within hospitals determines where the ICU appears in an organizational chart and to whom unit management is accountable. Thirty-six percent of the units were located organizationally within the hospital's department of medicine, while 23% were considered "free standing," having no departmental affiliation. Although units must have a medical director, the perception as to whether this director supervises the day-to-day operation was different in larger vs. smaller hospitals. In hospitals with less than or equal to 100 beds, 72% of the units were perceived to be supervised by the medical director, whereas in larger hospitals (greater than 500 beds), 81% of units were supervised. Study results indicated that medical directors in pediatric, neonatal, and burn units most often were perceived to supervise the unit. Presently, 63% of all ICUs responding are directed by an internist. The next largest group to direct ICUs were surgeons, followed by pediatricians. Pediatrician involvement tended to be exclusive in pediatric and neonatal units. Surgeons directed most surgical and neurologic units and were involved in 21% of mixed medical/surgical units. Internists predominated in medical units and in CCUs, as well as in combined medical/surgical/CCUs. Direction by anesthesiologists, although relatively infrequent, predominated in the surgical unit. Critical care medicine certification of the medical director and attending staff of the ICU increased as hospital size increased, although only 44% of all units stated that thei PMID- 1597042 TI - American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference: definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. AB - OBJECTIVE: To define the terms "sepsis" and "organ failure" in a precise manner. DATA SOURCES: Review of the medical literature and the use of expert testimony at a consensus conference. SETTING: American College of Chest Physicians (ACCP) headquarters in Northbrook, IL. PARTICIPANTS: Leadership members of ACCP/Society of Critical Care Medicine (SCCM). RESULTS: An ACCP/SCCM Consensus Conference was held in August of 1991 with the goal of agreeing on a set of definitions that could be applied to patients with sepsis and its sequelae. New definitions were offered for some terms, while others were discarded. Broad definitions of sepsis and the systemic inflammatory response syndrome were proposed, along with detailed physiologic variables by which a patient could be categorized. Definitions for severe sepsis, septic shock, hypotension, and multiple organ dysfunction syndrome were also offered. The use of severity scoring methods were recommended when dealing with septic patients as an adjunctive tool to assess mortality. Appropriate methods and applications for the use and testing of new therapies were recommended. CONCLUSION: The use of these terms and techniques should assist clinicians and researchers who deal with sepsis and its sequelae. PMID- 1597043 TI - Guidelines for program content for fellowship training in critical care medicine. Guidelines Committee; Society of Critical Care Medicine. PMID- 1597044 TI - Guidelines for the qualifications of a director of a fellowship training program in critical care medicine. Guidelines Committee; Society of Critical Care Medicine. PMID- 1597045 TI - Phospholipids and their inhibitors: a critical evaluation of their role in the treatment of sepsis. AB - OBJECTIVE: The clinical condition sepsis and its sequelae are caused by numerous mediators that are released by various cell types. The purpose of this review is to describe the results of various studies performed with agents that either inhibited or stimulated the synthesis of, or affected the receptor-binding characteristics of a specific class of these mediators, the phospholipids. DESIGN: Antagonists to platelet-activating factor and thromboxane A2 receptors, monoclonal antibodies to phospholipase A2, agents which increased levels of prostaglandins, and cyclooxygenase, lipoxygenase, and other specific pathway inhibitors, which block the production of leukotrienes and thromboxane A2, were used in the studies described to affect the physiologic correlates of sepsis animal models and human studies. DATA SOURCES: The matters discussed in this paper come from a wide variety of sources, including many broad-based clinical studies of humans with inflammatory disease. Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics. STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent discoveries. Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals. Clinical studies are generally of large numbers of patients showing overt signs of sepsis. DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including such major basic science journals as Science, and clinical journals such as the Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine. DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies. These contradictions are discussed in this review, and may often be due to the use of different protocols and definitions of the various clinical states. CONCLUSIONS: Increases of some mediators, such as platelet-activating factor, thromboxane A2, and the leukotrienes are associated with animal models of sepsis and seem to have a negative effect on the course of sepsis. Antagonists and blockers of these mediators increased survival in these studies. More research is needed to identify how these mediators of inflammation are associated with sepsis, and what the effects of blocking their actions will have on sepsis. PMID- 1597046 TI - Inhibitors of complement and neutrophils: a critical evaluation of their role in the treatment of sepsis. AB - OBJECTIVE: Damage to the vascular system is a major finding of sepsis and its sequelae. This damage is caused, in part, by the recruitment and adhesion of neutrophils to the endothelium and their release of destructive molecules. Mediators released by various cell types, including the neutrophil itself, control these destructive actions of the neutrophil. The complement system is one such group of mediators. Through the use of medications that decrease neutrophil activation and adherence and block complement activation, it may be possible to control the course of sepsis. DATA SOURCES: The issues discussed in this paper come from a wide variety of sources, including several broad-based clinical studies of humans with inflammatory disease. Many animal studies are discussed, along with some in vitro cell culture studies and work in molecular genetics. STUDY SELECTION: This article reviews a subject that is rapidly evolving, with frequent new discoveries. Thus, much of the article discusses research in basic science, particularly the use of experimental drugs in animals. Few clinical studies have been performed using these agents. DATA EXTRACTION: Most cited literature was found in reputable, peer review journals, including important basic science and clinical journals such as Science, Journal of the American Medical Association, New England Journal of Medicine, and Critical Care Medicine. DATA SYNTHESIS: Occasionally, contradictions do occur in the results of various studies. These contradictions are discussed and may often be due to different protocols and different definitions of the various clinical states. CONCLUSIONS: Pentoxifylline has been shown to decrease neutrophil adhesion and provides increased survival rate in various animal models of sepsis. Early studies regarding monoclonal antibodies to adhesion molecules are exciting. However, the possible effects of these agents in sepsis has yet to be studied. Drugs have been discovered that show potential to block the numerous destructive agents released by degranulating neutrophils. PMID- 1597047 TI - Therapeutic use of omeprazole for refractory stress-induced gastric mucosal hemorrhage. PMID- 1597048 TI - Hemodynamic confirmation of septic shock in disseminated tuberculosis. PMID- 1597049 TI - Percutaneous tracheostomy. PMID- 1597050 TI - What Humpty Dumpty meant. PMID- 1597051 TI - Nosocomial pneumonia in the critically ill. PMID- 1597052 TI - Hypertensive iridocyclitis associated with meningococcal infection. PMID- 1597053 TI - Life-threatening complications from percutaneous dilatational tracheostomy. PMID- 1597054 TI - Recognition of accidental arterial cannulation after attempted central venipuncture. PMID- 1597055 TI - Stress ulcer prophylaxis. PMID- 1597056 TI - Successful educational/developmental strategies used in a critical care residency program. PMID- 1597057 TI - Nursing alert: simultaneous use of heparin and nitroglycerin infusions. PMID- 1597058 TI - British nurses--we're only a language away. PMID- 1597059 TI - Work must be redesigned around the patient's needs. PMID- 1597060 TI - Automated external defibrillators: an update of additions to the ACLS algorithms. AB - Instruction in the use of the automated external defibrillator is now a mandatory component of ACLS certification. Here's a review of changes to the ACLS algorithm. PMID- 1597061 TI - Recognizing and treating torsade de pointes. PMID- 1597062 TI - Dealing with advance directives for critically ill adolescents. AB - Respecting the values and preferences of adolescents regarding treatment is an essential dimension of nursing practice. As public policy and societal thinking about the role of minors in healthcare decisions evolves, critical care nurses are in a pivotal position to provide leadership and guidance. Critical care nurses who care for adolescents should embrace the opportunity created by the PSDA to implement creative strategies for involving minors in decision making, seek improved methods of assessing decision-making capacity, and document the values and preferences of minors. PMID- 1597063 TI - Overcoming the obstacles to caring for the long-term critical care patient. AB - Caring for the critically ill long-term patient is a challenge. Although such patients must remain in the critical care environment because of the nursing expertise they require, they are often viewed as low-priority patients by the staff because of two factors. One factor relates to the nurse. Critical care nurses, typically action-oriented, function best during crisis intervention and are rewarded for technical skills and efficiency. The other factor relates to the patient. The critically ill long-term patient's needs are different from those of patients most often seen in critical care units; therefore, required nursing interventions are different. These interventions may not be within the nurse's usual repertoire of knowledge and skills and may also be physically and psychologically draining. Implementation of appropriate strategies has the potential for reducing length of stay, cost to the patient and the hospital, and stress for the critical care staff. PMID- 1597064 TI - Detection of right ventricular myocardial infarction in patients with inferior wall myocardial infarction. PMID- 1597065 TI - Mary Conover: a passion for reading the ECG wave. Interview by Michael Villaire. PMID- 1597066 TI - Incorporating critical care monitoring tools in your QA program. PMID- 1597067 TI - Evaluating quantitative research problems. AB - By focusing on criteria for evaluating quantitative research problems and by understanding their evolution from prior research and their placement within a theoretical context, nurses should realize that good research depends to a great degree on good questions. Unless an investigator has a "good, workable, significant topic, the most carefully and skillfully designed research project will be of no value. PMID- 1597068 TI - Ultrastructure of the marginal division in the rat striatum. AB - The discovery of a new subdivision in the striatum of the rat, the marginal division, has recently been reported. The marginal division is located at the caudal extent of the striatum, surrounding the rostrolateral border of the globus pallidus, and has different cellular morphology, immunohistochemistry and an efferent projection pattern from those of the main body of the striatum. In the present study, the ultrastructural organization of the marginal division was investigated. Most neuronal somata in the marginal division were fusiform in shape and had a large pale oval nucleus without in-foldings. There were four types of synapses in the marginal division: axo-somatic, axo-dendritic, axo spinous and axo-axonic. Both symmetric and asymmetric synapses were observed on the somata, dendrites, or dendritic spines. Most of the symmetric synapses contained pleomorphic vesicles, whereas the asymmetric ones contained mainly round vesicles. Individual axo-axo-spinous synapses, which were first described in the striatum, were also observed in the marginal division. These ultrastructural characteristics distinguish the marginal division from the rest of the striatum. PMID- 1597069 TI - Effects of cholecystokinin octapeptide on genetically determined seizure susceptibility. AB - Utilizing audiogenic seizure-prone P77PMC rats, the effects of cholecystokinin octapeptide (CCK-8) on genetic seizure susceptibility were studied in vivo, in cerebral cortical synaptosomes, and in cortical neuronal cell cultures. The results showed that CCK-8 could decrease seizure susceptibility, and that the K(+)-stimulated release of GABA in cerebral cortex synaptosomes from seizure prone animals was depressed. The presence of exogenous CCK-8 (10(-7) M) together with elevated K+ (25 mM) causes a higher increased magnitude in GABA release from synaptosomes (enhanced by 100%) and cell cultures (17 days in vitro, increased by 177%) derived from seizure-prone rats than the controls (increased by 42%, in synaptosomes; and 107% in cell cultures). These preliminary results raise the possibility that the developmental abnormalities in modulation effect of CCK-8 on GABA release in central nervous system may play a role causing greater seizure susceptibility in genetic seizure-prone rats. The analysis of the brain tissue level and gene-expression of CCK-8 will be the important step of further investigation. PMID- 1597070 TI - Hepatic arterial chemoembolization with CDDP microcapsules. Experimental studies. AB - After cis-diamminedichloroplatinum ethylcellulose microcapsules (CDDPmc) and unencapsulated CDDP were infused into the hepatic arteries of New Zealand rabbits, both CDDP concentrations in the circulating blood and in hepatic tissue were measured at different time intervals. In the rabbits infused with CDDPmc, the CDDP concentration was maintained at a high level for a significantly longer time in the hepatic tissue and the maximum CDDP level in the circulating blood was greatly reduced, as compared with those in the rabbits infused with unencapsulated CDDP. The tumoricidal effects of arterial infusion of CDDPmc were also evaluated in a model of liver tumor in rats. The therapeutic effects on rat liver tumor of CDDPmc were superior to those of unencapsulated CDDP and blank ethylcellulose microcapsules. The rats treated with CDDPmc showed a significantly lower tumor growth ratio, more extensive tumor necrosis and longer survival time. The results of this study indicate that CDDPmc is a more potential dosage from than conventional CDDP for hepatic arterial infusion in the treatment of liver cancer. PMID- 1597071 TI - The effect of tissue disaggregation methods on the clonogenicity of solid human tumor cells. AB - The effect of mechanical, enzymatic and combined disaggregations on the same tumor tissue (n = 154) to define variables related to clonogenic efficiency (CE) of human tumor clonogenic assay (HTCA) was examined. Overall, CE was highly associated with the percentage of malignant cells in the inoculative suspensions (P less than 0.001) and the total cell concentration plated (P = 0.03). However, there was no significant correlation between CE and the disaggregation method, type of tumor, cell viability, proportion of macrophages in the inoculum, or length of incubation (10 or 20 days). In addition, a higher CE was found in some nonadherent fractions when comparing the CE of the original plating suspensions to that of their nonadherent fractions. It is concluded that mechanical disaggregation is the simplest technique for obtaining the highest yield of malignant cells, which is a decisive factor for colony growth, and that an incubation time of 10 days and 1 x 10(6) cells per plate is the best condition for the human tumor clonogenic assay. PMID- 1597072 TI - Study of radiation dosage in esophageal carcinoma. AB - A series of 221 esophageal carcinoma patients admitted from 1983 to 1984 for radiotherapy was randomised into two groups. Group A was given 50 Gy/5 wk, 111 patients and Group B 70 Gy/7 wk, 110 patients. Three in group A and 11 in Group B did not complete their treatment due to adverse reactions. The 5-year survival rates of Groups A and B were 16.7% and 17.2% (P greater than 0.5). Because of the absence of excellent results and higher incidence of discontinuation of therapy in the 70 Gy group, the authors believe that the high dose regimen is not warranted in esophageal cancer. PMID- 1597073 TI - MRI-T2 values in the differentiation of recurrence and fibrosis after radiation of nasopharyngeal carcinoma. AB - The possibility of T2 values in the differentiation of local recurrence and irradiation fibrosis was studied prospectively in 36 patients with nasopharyngeal carcinoma (NPC) after radiotherapy. All the patients had a soft-tissue mass in the nasopharynx demonstrated by CT. Fourteen patients had tumor recurrence, 20 radiation fibrosis, 1 postradiation edema, and 1 inflammatory change. The control group consisted of 8 patients with untreated NPC. It was found that T2 was longer in patients with tumor than in patients with radiation fibrosis. We conclude that MRI may be used as a noninvasive method for differentiating radiation fibrosis from local recurrent NPC, but the prolonged T2 value of tumor is not specific and may be seen in radiation edema and infection. PMID- 1597074 TI - Studies on pathological morphology, clinical features and nuclear DNA contents by flow cytometry in adrenal neoplasms. AB - Pathological morphology, clinical features and nuclear DNA contents determined by flow cytometry (FCM) were studied in 11 cases of normal adrenals and 41 cases of adrenal neoplasms. It was found that despite differences in clinical manifestations and in degrees of cellular atypia of the adenomas their DNA contents were the same as in normal adrenals. On the other hand, the pheochromocytomas were benign in nature, but most of them (16/19) showed DNA aneuploidy and the DNA indices were correlated with their clinical and morphological features. PMID- 1597075 TI - Changes in hemorrheology in urticaria. AB - Hemorrheology was studied in 41 cases of urticaria, and platelet aggregation function in 37 cases. The whole blood viscosity in low shearing stress, plasma viscosity, fibrinogen level and platelet aggregation were found to be markedly increased (P less than 0.05 - P less than 0.005). The cause of high blood viscosity is discussed. It is considered as the results of high plasma viscosity and increased RBC aggregation. The hemorrheological changes coincided with the hemodynamic changes seen in cutaneous microcirculation: slow granular blood stream, and aggregation of erythrocytes. PMID- 1597076 TI - Rational use of methotrexate in maintenance therapy of childhood acute lymphoblastic leukemia. AB - This study was undertaken to research the pharmacokinetics and bioavailability of methotrexate (MTX). Plasma concentrations were measured by fluorescent spectrometry in 20 normal SD rats, and 28 measurements were done in children with acute lymphoblastic leukemia (ALL). Both rats and children were divided into four groups. Either 20 mg/m2 or 40 mg/m2 of MTX was given IV or PO in each group. The plasma MTX concentrations were measured within 8 hours after administration. The concentration versus time curves were fitted by MCPKP program for pharmacokinetics (PK) and the parameters calculated. After PO administration, the peak concentration, duration of therapeutic concentration and bioavailability were much lower than that after IV administration. The differences were more obvious at 40 mg/m2 dosage. The higher the PO dosage, the lower the bioavailability. Absorption of PO MTX in children with ALL varied widely and uniform concentration was not expected even after equal dosage. Drug concentration was not necessarily increased with dosage. It is our conclusion that drug concentrations and PK parameters should be measured in patients receiving PO MTX therapy. PMID- 1597077 TI - Tumors of the heart. An analysis of 79 cases. AB - There were 79 cases of cardiac tumors seen from 1957 to July 1988. 49 (62.0%) of them were benign and 30 (38.0%) malignant. All the 49 benign tumors except 2 were surgically excised and found to be myxoma. Of them, 18 patients were male and 31 female. 85.7% of the tumors were located in the left atrium, 12.2% in the right atrium and 2.0% in the left ventricle. Palpitation, dyspnea, chest oppression, fever, episodes of syncope and hemiplegia, cough, diastolic and systolic murmurs at the apical or tricuspid area were the common symptoms and signs. Atrial fibrillation was found only in 2 cases. Echocardiographic findings were diagnostic while ECG and X-ray findings were nonspecific. Four patients died after operation. Of the 30 cases of malignant tumors, 15 were secondary tumors metastasized mainly from the lung or mediastinal malignancies. Of 11 primary tumor cases (7 males and 4 females), 3 were malignant lymphoma, 2 mesothelioma of pericardium, 2 malignant myxoma, 1 angiosarcoma, 1 leiomyosarcoma, 1 fibrosarcoma and 1 rhabdomyosarcoma. Another 4 cases were not studied histopathologically. The clinical manifestations, ECG and X-ray findings of the 11 primary tumors were nonspecific but echocardiography was helpful to the diagnosis. Six patients were operated on and 1 died during hospitalization. PMID- 1597078 TI - Hemodynamic assessment of intravenous Isosorbidi Dinitras in coronary heart disease. AB - This study investigates the systemic hemodynamic effects of intravenous Isosorbidi Dinitras, Isoket (ISDN) in 20 patients with coronary arterial disease to test the validity of the hypothesis concerning the relief of myocardial ischemia. Patients were eligible for the study if they had angina with coronary angiographic records or if they were cases of post-myocardial infarction. Before and after ISDN infusion the following measurements were recorded or calculated: heart rate (HR); systolic, diastolic and mean aortic pressure (ASP, ADP, AP); systolic and mean pressure of the left ventricle (LVSP, LVP); end-diastolic pressure in the LV (LVEDP); left ventricular contractility (dp/dt max); the double products (DP, HR x LVSP) and myocardial perfusion pressure in the LV (LVPP). After ISDN the ASP, AP and LVEDP decreased while HR, ADP, dp/dt and DP showed no significant changes. However, LVEDP was significantly decreased from 20 +/- 7 to 12 +/- 5 mmHg (P less than 0.01) with increased LVPP from 49 +/- 12 to 56 +/- 13 mmHg (P less than 0.01), which may be favourable for the relief of myocardial ischemia. There was no significant change of dp/dt max with decreased LVEDP after ISDN. It is suggested that the left ventricle can maintain normal performance at lower intracardial volume (preload) in these patients. PMID- 1597079 TI - Selective total vascular occlusion for major hepatic resection. AB - Selective total vascular occlusion for the resection of large tumors on the right lobe of the liver or central hepatic tumors was described. The occlusion of the portal triad, infrahepatic vena cava and the total hepatic circulation was selectively used in combination to control bleeding in the process of hepatectomy. Within a year, major resection was successfully performed with this technique on 10 patients (extended right lobectomy 4 patients, right lobectomy 4, central segmentectomy 2). The mean duration of total vascular exclusion was 19.35 +/- 19.32 minutes and mean blood transfusion requirement was 7 +/- 4.5 units during surgery. PMID- 1597080 TI - Soft tissue release on the concave side in the treatment of scoliosis. A preliminary report of 23 cases. AB - Since February 1982, 23 patients with scoliosis were treated by releasing the soft tissues on the concave side and plaster spinal fusion jacket. Of these patients, 13 had congenital scoliosis and 10 idiopathic scoliosis. Follow-up for 1 to 8.5 years showed that the results of correction were satisfactory. The maximum degree of correction of the main curve in this series was from 74 degrees (Cobb method) before treatment to 3 degrees after treatment. The maximum rate of correction was 97.3%. PMID- 1597081 TI - Arrythmogenic right ventricular dysplasia. A case report. PMID- 1597082 TI - An overview of molecular parasitology in China. AB - Molecular cloning technology has been gradually used in the studies of parasitic diseases in China since 1986. The information briefly reviewed here deals mainly with: (1) the molecular cloning of immunogen genes related to Schistosome and Plasmodium; (2) a diagnostic DNA probe for malaria and toxoplasmosis; and (3) DNA probes for inter- and intra-specific differentiation of Leishmania, Schistosome, Entamoeba, etc. PMID- 1597083 TI - Effects of cordyceps sinensis on natural killer activity and colony formation of B16 melanoma. AB - This paper reports the study on the effects of the ethanol extract of Cordyceps sinensis (CS-II), a potent herbal tonic, on murine and human in vitro natural killer cell (NK) activities and on murine in vivo NK activity (by 125I clearance assay), and on colony formation of B16 melanoma in mouse lungs. The results revealed that: 1. the in vivo and in vitro NK activities of mouse were both significantly augmented by intraperitoneal (ip) injection of CS-II. Besides, the inhibition of mouse NK activity by cyclophosphamide (Cy) was prevented following the administration of CS-II; 2. the in vitro NK activity of human peripheral blood mononuclear cells (PBMs) was elevated by preincubation of PBMs with CS-II; and 3. the colony formation of B16 melanoma in mouse lungs was reduced significantly by ip pretreatment of the mice with CS-II. This study indicates that CS-II may be used as an immunopotentiating agent in treating cancer and immunodeficient patients. PMID- 1597084 TI - [Change and current status of surgical treatment of colorectal cancer. Report of experiences of the Erlangen Surgical University Clinic]. PMID- 1597085 TI - [Radical treatment with limited resection in cancer surgery of the gastrointestinal tract]. PMID- 1597086 TI - [Principles of multi-modality therapy in tumors of the gastrointestinal tract]. PMID- 1597087 TI - [Intraoperative radiotherapy of malignant tumors of the gastrointestinal tract]. PMID- 1597089 TI - [Prevention of thromboembolism in general surgery]. PMID- 1597088 TI - [Pathophysiology and pathogenesis of venous thrombosis]. PMID- 1597090 TI - [Prevention of thromboembolism in trauma surgery and orthopedics]. PMID- 1597091 TI - [Treatment of manifest thrombosis]. PMID- 1597092 TI - [Cervical interventions on the airway and esophagus in infiltrating thyroid cancer]. AB - In 1989 und 1990 a resection within the region of the cervical airways and/or oesophagus was performed for an infiltrating tumor in 9 out of 95 patients (9.5%) suffering from thyroid carcinoma and in one patient with lymph node metastases from a carcinoma of the uterine cervix. There was no operative mortality. One patient died six weeks after resecting the anterior wall of the trachea of an intratracheal arterial bleeding due to radiation therapy. In one case the reconstruction of the trachea was performed with autologous material, in three patients alloplastic material was used. The oesophagus was reconstructed preferably by means of free microvascular jejunum autografts (n = 4), using a colon interposition in another two patients. In locally advanced differentiated and medullary thyroid carcinoma curative operations of the cervical hollow organs using microsurgical techniques can be performed with an acceptable operative risk and good functional results. They may markedly improve the otherwise limited prognosis of the disease. PMID- 1597093 TI - [Disorders of hemostasis after polytrauma. On the extent of intrinsic fibrinolytic activity in the preclinical phase]. AB - Coagulation disorders are of utmost importance in emergency surgery as well as for secondary organ failure of polytraumatized patients. In order to get hold of the early onset of these disorders, blood samples were harvested from 20 randomly selected patients (Injury Severity Score mean = 36.7 +/- 10.5) on the scene of emergency (mean = 18 [10-29] min after trauma) and at the time of hospital admission (mean = 78 [58-98] min after trauma). In addition to the activation of intravascular coagulation and the consumption of physiological inhibitors, high amounts (10- to 50-fold above normal) of degradation products (FgDP, FbDP, TDP, D dimers) are present on the scene, already. The influence of hemodilution due to high-volume resuscitation is discussed. PMID- 1597094 TI - [Pressure behavior in muscle compartments of the foot in defined stress, metatarsal and ankle joint fractures]. AB - In addition to the importance of compartment syndrome in the lower leg, a growing interest is being shown in the muscle compartments of the foot region. The standard pressure rates in the muscle compartments of the foot comprise up to 4 kPa for men and up to 2.5 kPa for women. During graded exercise (n = 9) on the treadmill the pressure increased in line with the strain and declined again rapidly when the exercise stopped without showing any significant differences in pressure between the muscle compartments studied. In metatarsal and ankle joint fractures post-traumatic pressures were found which were as high as or higher than after 20 minutes on the treadmill and would make the development of a compartment syndrome possible. This points to the necessity of measuring the pressure in the muscle compartments of the patient's foot when there is a clinical suspicion of a compartment syndrome. PMID- 1597095 TI - [Hemorrhoidectomy--a simple operation? Incontinence, stenosis, fistula, infection and fatalities]. AB - Hemorrhoidectomy is not a simple procedure. Hemorrhoids develop as hyperplastic formations of an important part of the anorectal organ of continence, i.e., the corpus cavernosum recti. This organ segment is analogous to tissue structures found in the tongue of certain birds which are used for hulling seeds. Well meaning, complete resection of the corpus cavernosum will inevitably result in incontinence. Only operative techniques which resect exclusively those segments of the hemorrhoidal tissue adjacent to the muscle layer in the anal canal are adequate. These procedures will spare sufficient tissue of the corpus cavernosum to allow a safe segmental resection of this structure and at the same time permanently eradicate the hemorrhoids. In the present paper, the treatment of 53 patients with postoperative incontinence and of others with stenoses, fistulas and pelvic infections is discussed. Fatalities have never been reported in the literature following operative hemorrhoidectomy, however, have occurred after "banding" procedures and after injection therapy. PMID- 1597096 TI - [Surgical thoracoscopy--indications and technique. Early results in spontaneous pneumothorax]. AB - The use of minimally invasive techniques in the thoracic cavity allows for the application of operative techniques through endoscopic ways, avoiding the functional burdening of a thoracotomy. Indications of operative thoracoscopy are mentioned. Endoscopic surgical techniques are described. For example, the therapy of spontaneous pneumothorax can be carried out in its entirety by endoscopic leak ligature, wedge resection of the lung and parietal pleurectomy. Three of the 49 patients with spontaneous pneumothorax suffered from an early recurrence after thoracoscopic treatment (6.1%). Long-term results are still outstanding. The final merit of the method cannot yet be set. PMID- 1597097 TI - [Tikhoff-Linberg scapulo-humeral resection]. AB - There is a trend away from amputation to salvage procedures for limb cancer. An effective adjuvant chemotherapy and the development of diagnostic imaging allow the surgeon to be more confident and conservative with a limb-salvage procedure. The Tikhoff-Linberg resection is a limb-sparing option to be considered for tumors of the proximal humerus and shoulder girdle. There are three different variants of the procedure published in the literature. An exact classification of the local extent of disease is necessary to indicate the variant of Tikhoff Linberg resection which will promise the best functional result without loss of oncological adequacy. PMID- 1597098 TI - [Calcified renal artery aneurysm--ex situ resection and reconstruction of segment arteries with branches of the internal iliac artery]. PMID- 1597099 TI - [Pseudo-Hirschsprung disease in the adult--a case of an ileo-anal pouch?]. PMID- 1597100 TI - Focusing on patient outcome: case management in the 90's. PMID- 1597101 TI - Third level hemodynamics: guiding clinical decisions. AB - Hemodynamic monitoring is one of the most frequently used technologies in critical care nursing. But how often do critical care practitioners consider the underlying reason for monitoring these variables? What really is the oxygen balance in the cell? How does oxygen supply and demand figure into the hemodynamic equation? This article demonstrates how the imbalance of oxygen supply and demand at the cellular level is important to understanding the patient's hemodynamic status. It is followed by a continuing education packet you can use to teach the cellular principles of hemodynamics. PMID- 1597102 TI - The Safe Medical Device Act: nursing implications. AB - The Safe Medical Device Act places a legal responsibility on health care practitioners to assess and report malfunctioning medical equipment. As a result of this law, the Food and Drug Administration (FDA) will for the first time have direct regulatory authority over hospitals. Today's complex and technological critical care setting requires that the nurse understand the legal and professional responsibilities imposed by this Act. PMID- 1597103 TI - A decision-making algorithm for blood pressure measurements. AB - Reliance on invasive blood pressure techniques can be problematic for nurses working in critical care units, as discrepancies are frequently noted between cuff and invasive blood pressure readings. Critical care nurses need a repertoire of decision-making techniques that assist them when they are caring for clients with this type of discrepancy. This paper describes an algorithm based on analytical techniques which is helpful to the nurse in making decisions about whether the invasive or noninvasive pressure is accurate. PMID- 1597104 TI - Developing self-scheduling in critical care. AB - Self-scheduling is a staffing method that delegates the control and the responsibility for generating a schedule to the staff nurses. This article focuses on what motivated the staff of a combined Cardiovascular Surgical Intensive Care and Stepdown Unit to implement self-scheduling and the improved job satisfaction that resulted. PMID- 1597105 TI - Administering pain medication for a terminal patient. Part 1: The ethical case. Part 2: Case analysis. AB - This is the case of a middle age man who was admitted to the intensive care unit (ICU) in respiratory failure. The nurses questioned their role in giving a medication to help the ventilatory-dependent patient to be more comfortable when the ventilator was removed at his request. Following the case is an ethical analysis of this situation. PMID- 1597107 TI - Enhancing learning through the use of games. AB - Incorporating a game into the critical care curriculum is an alternative teaching strategy with beneficial outcomes. Games promote team work, reduce stress and generate enthusiasm for learning. Not only does this instructional mode enhance the learning process, but it also makes it fun! PMID- 1597106 TI - Developing the trauma nurse case manager role. AB - The case manager serves as the coordinator of all care for a specific caseload of patients throughout an episode of illness. This role includes management, clinical, consultation, education, and research roles. Case management is especially important to implement for trauma patients who otherwise have wide variations in outcomes because of the trauma and concomitant social problems. This author describes how the case management role can be implemented, includes a sample job description of the multiple-responsibilities, and provides a case study demonstrating the case manager's role. PMID- 1597108 TI - [Metal or plastic endoprostheses in malignant obstructive jaundice. A randomized and prospective comparison]. AB - In a prospective randomized trial 58 patients (24 men, 34 women, mean age 67 +/- 13 [42-89] years) with inoperable malignant jaundice were treated with synthetic (S; n = 29) or expanding metal endoprostheses (M; n = 29). After endoscopic retrograde cholangiopancreatography patients were divided into a group with hilar (K: n = 7; M: n = 6) or distal involvement (K: n = 22, M: n = 23). In two cases with hilar involvement (28%) a synthetic endoprosthesis could not be implanted, while early prosthesis occlusion (after 2 days) was observed in one case. But in this group it was possible to implant all metal stents. In the group with distal involvement both synthetic and metal endoprostheses were successfully implanted. In the M group the proportion of patients with prosthesis failure (13.6%) was significantly higher than in the S subgroup (40.9%). The cholangitis incidence was 9% in the M group, significantly less (P less than 0.05) than in the K group (40.9%). Duration of hospital stay to treat prosthesis-related complications was significantly less in the M group (average 2.9 days) than the K group (12.9 days). It would be a great advance in palliative tumour treatment if it were possible significantly to reduce, by means of metal stents, the incidence of late cholangitis and the duration of hospital stay necessary to treat late complications. But improvement in the technique of implanting metal stents would be essential before their general use in distal lesions can be recommended. PMID- 1597109 TI - [Spontaneous splenic rupture in acute malaria tropica]. AB - A 44-year-old man developed bouts of fever (up to 40 degrees C) seven days after returning from a holiday in Kenya. Malaria prophylaxis with chloroquine had been correctly undertaken. Concentrations of lactate dehydrogenase and total bilirubin were raised (493 U/l and 3.55 mg/dl, respectively). Blood smear revealed the ring forms of Plasmodium falciparum. Thereupon the patient was given mefloquine in decreasing doses (750/500/250 mg) at intervals of 8 hours. The following night he had a circulatory collapse and complained of pain on pressure, especially in the left upper abdomen. Abdominal sonography showed a slightly enlarged spherical spleen with an echo-poor band and fluid collection in the rectovesicular pouch, indicating rupture of the spleen. A splenectomy was performed. Subsequently the number of malaria organisms in the blood smear gradually fell and signs of haemolysis disappeared. Splenic rupture is a very rare complication of acute malaria. It is presumably caused by marked stasis in the splenic sinuses with deformed parasite-containing red blood cells. PMID- 1597110 TI - [Anti-basement membrane antibody disease of the lungs without clinical kidney involvement]. AB - Anaemia (haemoglobin 10.7 g/dl) and small spotty infiltrates in both lungs were found in an 18-year-old man who had increasing haemoptysis over the preceding 3 weeks. Bronchoscopy revealed diffuse bilateral pulmonary haemorrhage. Further diagnostic measures provided no evidence of involvement of other organs, in particular the kidneys. The demonstration of anti-basement membrane antibodies confirmed the diagnosis of a disease within the group of immune-induced alveolar haemorrhage. The radiological signs in the lungs regressed over 3 weeks of administering prednisone, initially 100 mg daily, then 60 mg daily, and the patient was discharged. While being treated as an out-patient, with reduction of prednisone to 10 mg daily, the haemoptysis recurred so that a single dose of cyclophosphamide, 1.5 g, was added to the immunosuppressive treatment. There was no further haemoptysis and the prednisone was discontinued after having been given for 15 months. The patient has now been in complete clinical remission for 3 years and anti-basement membrane antibodies are no longer demonstrable. At no time was there any evidence of renal involvement in the sense of the classical Goodpasture's syndrome. PMID- 1597112 TI - [Nocturnal asthma]. PMID- 1597111 TI - [Digitalis intoxication]. PMID- 1597113 TI - [The medical care law and its transformation in hospital practice]. PMID- 1597114 TI - [Circadian fluctuations of the cortisol level]. PMID- 1597115 TI - [Varicose phlebitis of the vena saphena magna]. PMID- 1597116 TI - [Oxygen radical formation in pulmonary sarcoidosis. The signs of early macrophage activation]. AB - Oxygen radical formation of alveolar macrophages (by luminogenic substrate intensified chemiluminescence) and the concentrations of phagocyte products myeloperoxidase, elastase and lactoferrin, as well as alpha-proteinase inhibitor and albumin were measured in bronchoalveolar lavage fluid of 28 patients with pulmonary sarcoidosis. There were 15 men and 13 women (mean age 41 [18-62] years), 10 of them with sarcoidosis I, 10 with clinically active sarcoidosis II and 8 with inactive sarcoidosis II. Six healthy persons served as controls. The purpose of the study was to demonstrate the extent of correlation between macrophage activity and stage of sarcoidosis. Patients in stage I had significantly higher luminescence (346 +/- 253 relative light units [RLU] per second) than the controls (117 +/- 29 RLU/s; P less than 0.02). But the difference between controls and patients in clinically active stage II (294 +/- 75 RLU/s) was not significant and the luminescence in patients with clinically inactive stage II was within normal range (119 +/- 33 RLU/s). The concentrations of proteins measured in the lavage fluid was increased, independent of the site of formation. These data indicate that in pulmonary sarcoidosis there exists, early and independent of stage, a marked activation of alveolar macrophages with increased production of oxygen radicals and a resulting increase in permeability of the alveolo-capillary membrane. PMID- 1597117 TI - [C-reactive protein in the urine. The differential diagnosis of renal functional disorders following kidney transplantation]. AB - A prospective study was undertaken in 73 patients (24 women, 49 men; mean age 47.9 [21-64] years) after renal transplantation to discover whether the presence of C-reactive protein in urine (CRPu) and its serum concentration (CRPs) are of value in the differential diagnosis of abnormal function in the transplanted kidney. CRPu concentration was measured with a highly sensitive immunoluminometric assay (minimal threshold value 6 micrograms/l). CRPu was demonstrated in 36 histologically proven rejection episodes and 21 bacterial infections proven by culture. In contrast, no CRPu was demonstrated when the course was normal and in individual cases of cyclosporin renal toxicity, as well as in 27 of 34 cases of cytomegalovirus infection. In addition, the CRPs to CRPu ratio was a sensitive means of distinguishing between rejection (CRPs/CRPu less than 1) and bacterial infection (CRPs/CRPu greater than 1). Determining CRPu concentration thus proved to be useful in the initial monitoring of renal transplantation before starting any specific urinary protein diagnosis, as well as (together with CRPs) in the diagnosis of severe posttransplantation complications. PMID- 1597119 TI - [The diagnosis of primary aldosteronism]. PMID- 1597118 TI - [IgG-lambda-type multiple myeloma with plasma-cell pericardial effusion and terminal plasma-cell leukemia]. AB - Monoclonal gammopathy of type IgG-lambda (IgG concentration 27.8 g/l) was discovered by chance in a 66-year-old woman with aortic and mitral valve disease. The patient declined any further diagnostic procedures. Three months later she experienced severe pain in the lumbar spine and developed decompensated cardiac failure with pulmonary and ankle edema. The IgG concentration had risen to 50.5 g/l. Echocardiography showed a large pericardial effusion and 600 ml of bloodstained fluid containing numerous plasma cells was aspirated (total protein 81.8 g/l, gamma-globulin 38.9%). Iliac crest biopsy showed diffuse infiltration with polymorphic plasma cells, but the differential count in peripheral blood was unremarkable. Multiple myeloma of Stage IIa was diagnosed and she was given cytostatic therapy with 17.5 mg melphalan and 112 mg methylprednisolone daily by mouth (for 4 days at intervals of 6 weeks). Though at first the IgG concentration fell, it later rose again. The beta 2-microglobulin level was raised at 30 mg/l. After three cycles of chemotherapy the patient complained of severe pain in the hips and thighs. The blood film now showed numerous, predominantly immature plasma cells. A few days later, having been ill for four months in all, she died, showing all the signs and symptoms of plasma cell leukaemia. PMID- 1597120 TI - [Hypercholesterolemia in old age--to treat or not?]. PMID- 1597121 TI - [The right to inspect the records in medical insurance expert testimony. The judgement of the Frankfurt Higher Regional Court of 28 May 1991]. PMID- 1597122 TI - [Recurrent benign aphthosis]. PMID- 1597123 TI - [Hyperdense cerebral focal lesions in magnetic resonance tomography]. PMID- 1597124 TI - [The echocardiographic demonstration of the embolization of a right atrial thrombus]. PMID- 1597125 TI - [Ozone and bronchial asthma]. PMID- 1597126 TI - Efficacy of oxime plus atropine treatment against soman poisoning in the atropinesterase-free rabbit. AB - The oximes pralidoxime chloride (2-PAM), MMB4, and HI-6 were evaluated in combination with atropine as treatments against soman poisoning in atropinesterase-free rabbits. Animals were challenged i.m. with 2 x LD50 soman and treated at the onset of toxic signs with 50 mumols/kg of oxime and 5 or 13 mg/kg atropine. Survival and time to death were compared at 48 hours post-soman challenge. Survival rates in MMB4 and HI-6 treated animals were higher than in 2 PAM-treated animals. The increase in survival was significant at the 13 mg/kg dose of atropine. MMB4 and HI-6 also significantly delayed time to death after soman compared to 2-PAM. The results suggest that MMB4 and HI-6 have potential as useful oximes for treating soman poisoning. PMID- 1597127 TI - Acetylcholinesterase inhibition and anti-soman efficacy of homologs of physostigmine. AB - Inhibition of acetylcholinesterase (AChE) activity by physostigmine (PHY) is reversible due to spontaneous decarbamylation. Physostigmine has been shown to be effective as a pretreatment against potent anticholinesterase poisons (e.g., soman) in experimental animals, yet it is short acting and causes undesirable side effects in mammals. The two-fold purpose of this study was 1) to determine whether extension of the N-substituted alkyl chain (N-SAC) of PHY from N-methyl to N-ethyl (I), N-propyl (II), N-isopropyl (III), N-butyl (IV) or N-heptyl (V) affects anti-AChE potency and spontaneous decarbamylation of inhibited AChE of guinea pig blood in vitro and in vivo, and 2) to see whether chain extension affects efficacy as pretreatment in poisoning by soman. The in vitro AChE inhibition studies were done using whole blood incubated at 37 degrees C for 30 min. All 5 homologs possessed anti-AChE activity with I50s ranging from 1.1 to 27.6 x 10(-7)M; compound III was the least potent in vitro and in vivo. Lengthening of the N-SAC of PHY markedly extended the duration of anti-AChE activity when compared to PHY, but rendered the modified compounds ineffective as pretreatments against soman. These data support the premise that the decrease in decarbamylation rates observed upon extending the N-SAC of PHY is responsible for the loss of effectiveness of pretreatment regimens against soman. Perhaps, these homologs of PHY may have potential use in instances where sustained action of acetylcholine is required at cholinergic junctions because of disease conditions or drug overdosage. PMID- 1597128 TI - Effects of dichloroglyoxime on isolated guinea-pig smooth muscle and atrium. AB - The effects of dichloroglyoxime (DCG) on isolated rings of aorta, main pulmonary artery, trachea and spontaneously-beating atrium of guines-pig were studied. DCG caused concentration- dependent relaxation of the epinephrine-contracted aortic and pulmonary artery rings and of the tone of tracheal rings. Propranolol caused a slight shift to the right in the concentration-effect curves of DCG on these preparations. Quinacrine, an inhibitor of the release of arachidonic acid and its metabolites, caused a significant shift to the right in the concentration-effect curves of DCG on the three preparations. Low concentrations of DCG increased the beating rate of the atrium, an effect which was blocked by propranolol but not by quinacrine whereas large concentrations decreased the beating rate, an effect which was not significantly affected by propranolol or by quinacrine. DCG also caused a concentration-dependent decrease in the contractility of the atrium and this effect was only slightly affected by propranolol or quinacrine. These observations suggest that the relaxant effect of dichloroglyoxime on the smooth muscle may not be mediated by the stimulation of beta adrenoceptors specifically although a nonspecific interaction with these receptors or with the contractile machinery of the cell cannot be excluded. Data with quinacrine suggest that the effects may be mediated by the release of an inhibitory metabolite of arachidonic acid. The results further suggest that in the atrium the effects of DCG may not be specific and they may be partially mediated by the release of catecholamines from the nerve endings. PMID- 1597129 TI - Kinetic and inhibitor studies of acetaminophen and zidovudine glucuronidation in rat liver microsomes. AB - The antiviral drug zidovudine (ZDV) and the analgesic and antipyretic agent acetaminophen (AP) are both biotransformed in the liver of humans to ether glucuronides. A previous clinical trial of ZDV suggested the potential for a clinically significant interaction between AP and ZDV, probably based upon competing hepatic metabolism. To study the mechanism of this potential competition between AP and ZDV as substrates for uridine diphosphoglucuronyltransferase (UDPGT), enzyme kinetic studies were performed using rat liver microsome preparations. Cross inhibition studies demonstrated that AP glucuronidation was competitively inhibited by ZDV, while ZDV glucuronidation was slightly inhibited by AP in a noncompetitive interaction. PMID- 1597130 TI - Immunosuppression and cancer: the ciclosporin case. AB - Experimental and clinical data relevant for the evaluation of the carcinogenic potential of the immunosuppressant ciclosporin are reviewed. Ciclosporin binds reversibly to the cytosolic receptor protein ciclophilin. Ciclophilin is likely involved in the blockade of lymphocyte activation-induced gene transcription of various growth factors, especially interleukin-2. The drug has no effect on the transcription of housekeeping genes nor does it activate any gene. Ciclosporin may inhibit tumor cell growth, notably those which are growth factor dependent. At high concentration virus-transformed cells, especially Epstein-Barr-infected B lymphocytes, may escape the control of specific cytotoxic T-lymphocytes. Ciclosporin has no genotoxic activity, and has no DNA-binding property. In experimental studies ciclosporin did not cause cancer in the absence of an initiating event (e.g. chemical mutagen). However, by its immunosuppressive property, the drug may allow the growth of initiated tumor cells in vivo, an effect which is dose-dependent. In clinical use ciclosporin immunosuppression is associated with an increased incidence of lymphoproliferative disorders and other malignancies particularly of the skin when compared with a normal, not immunosuppressed population. Conventional immunosuppression (azathioprine, antilymphocyte globulin, prednisone) also demonstrates comparable risks to develop tumors. Lymphoproliferative lesions regress after dose reduction or cessation of treatment. Furthermore, combinations of various immunosuppressants with associated 'over-immunosuppression' may result in a higher incidence of viral infection and malignancy. In summary, chemical immunosuppression carries the intrinsic risk of tumor growth. In the case of ciclosporin this effect is dose dependent. Thus, the risk may be reduced by low dosage and by avoiding combination therapies with additional immunosuppressants. PMID- 1597131 TI - Remembrance: neuroendocrinology and aging. A perspective. PMID- 1597132 TI - Remembrance: tracing the glucose tracer dilution technique for measuring glucose turnover. PMID- 1597133 TI - Cortisol regulates secretion and pituitary content of the two gonadotropins differentially in female rats: effects of gonadotropin-releasing hormone antagonist. AB - To determine if LH and FSH respond to cortisol exposure the same way in females as they do in males, metestrous females were implanted with cholesterol or cortisol (F) subcutaneously, and either ovariectomized or left intact 4 days later. Tail vein injections of 1000 ng of GnRH in saline, or saline alone, were given 4.5, 23.5, or 47.5 h after the time of ovariectomy. Animals were killed 30 min after the injections at 5, 24, and 48 h after surgery. F attenuated the postovariectomy increase in serum LH at 48 h. F also suppressed GnRH-stimulated LH release 24 and 48 h after surgery in ovariectomized animals and in intact animals at 48 h. Pituitary content of LH was increased moderately by F at 5 h. These effects of F are similar to those seen in males. In contrast to LH, F increased serum FSH in intact females and suppressed levels in ovariectomized animals at 24 and 48 h, while inducing a remarkable increase in pituitary FSH content at all three times. These divergent effects of F on serum FSH (suppression in gonadectomized and stimulation in intact groups) were not seen in males, and the increase in pituitary FSH as a result of exposure to F was much more profound and reliable in females than in males. To determine if the F induced increase in pituitary FSH was dependent on endogenous secretion of GnRH, intact metestrous females were implanted with either cholesterol or F pellets. Each implant group received sc injections of 100 micrograms GnRH antagonist or control injections every 48 h beginning at the time of steroid implantation. Animals were killed 5 days after implantation. The antagonist suppressed both serum and pituitary LH. F also suppressed serum LH levels, but had no effect on pituitary content of LH. Neither the antagonist nor F affected serum FSH. F greatly increased pituitary content of FSH in the presence or absence of GnRH antagonist. These data suggest that 1) LH responds to F treatment in a similar way in females and males; 2) pituitary FSH content is more sensitive to the enhancing effect of F in females than in males; 3) the ability of F to increase pituitary FSH in females is not dependent on GnRH. PMID- 1597134 TI - The effect of 22-oxacalcitriol on serum calcitriol. AB - 1,25-Dihydroxyvitamin D3 (1,25D) regulates its own levels in circulation by affecting its rates of synthesis and degradation, 22-Oxacalcitriol (OCT), a vitamin D analog with low calcemic activity, decreases circulating PTH levels, one of the regulators of renal 1 alpha-hydroxylase, and stimulates vitamin D degradation in vitro. The purpose of this study was to examine the effects of OCT administration on serum levels of 1,25D. In normal rats, OCT administration (4 200 ng, ip, daily for 5 days) caused a dose-dependent reduction in serum calcitriol levels. At a dose of 200 ng, OCT reduced serum 1,25D from 34.5 +/- 2.7 to 10.9 +/- 0.7 pg/ml (P less than or equal to 0.01) without significant changes in ionized Ca or phosphorus levels. The contribution of the suppression of PTH by OCT to the reduction of serum 1,25D was examined by administering OCT to parathyroidectomized (PTX) rats. Two hundred nanograms of OCT, ip, daily for 5 days significantly reduced serum calcitriol from 29.7 +/- 7.6 to 9.1 +/- 0.5 pg/ml (P less than or equal to 0.01) in rats fed a normal calcium diet. Because OCT increased total calcium (TCa) in this group from 7.4 +/- 0.1 to 9.5 +/- 0.3 mg/dl, similar doses of OCT were given to PTX rats fed a calcium-deficient diet. OCT decreased 1,25D from 58.9 +/- 8.9 to 10.3 +/- 0.4 pg/ml and increased TCa from 4.8 +/- 0.2 to 7.4 +/- 0.1 mg/dl. Comparison of serum 1,25D for identical TCa levels in PTX rats (normal calcium diet controls vs. calcium-deficient diet, OCT-treated) clearly indicates that OCT per se reduced serum 1,25D. Further support for a direct effect of OCT was provided by studies in PTX rats fed a low phosphorus diet. OCT decreased serum 1,25D from 125.8 +/- 15.6 to 10.9 +/- 0.6 pg/ml without significant changes in TCa. To further characterize the mechanisms involved in this effect, similar studies were performed in six normal dogs. Intravenous administration of 0.75 micrograms OCT every other day for 1 week decreased serum calcitriol from 25.4 +/- 3.2 to 12.2 +/- 1.3 pg/ml (P less than or equal to 0.002). Ionized Ca and phosphorus remained unchanged. Despite the short half-life of OCT in the circulation, 1,25D levels returned to basal concentrations 96 h after the last dose of OCT.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597136 TI - Influence of ovarian steroids on relaxin-induced uterine growth in ovariectomized gilts. AB - This study examined the influence of ovarian steroids on the uterotropic actions of relaxin (RLX) in ovariectomized prepubertal gilts. Ovariectomized gilts received (im) corn oil (CO), estradiol benzoate (EB), or EB and progesterone (P) for 0-16 days. Steroid administration was patterned to approximate the plasma concentrations of endogenous ovarian steroids observed during 1) the follicular phase (EB), 2) luteal phase (EB+P), and 3) early pregnancy (EB+P+EB). Half of each group also received PBS or 0.5 mg RLX every 6 h for 54 h, coinciding with the final 2 days of the experimental period. After hysterectomy, uterine tissues were analyzed for water, dry matter, protein, DNA, glycosaminoglycans (GAGs), and collagen contents. Administration of EB or P increased uterine weight 5- to 6 fold, but no differences were observed between EB+P- and EB+P+EB-treated gilts. Cotreatment with RLX enhanced steroid-induced uterine growth 40-70%, and RLX stimulated growth in CO- and EB+CO control gilts 2- to 3-fold. The water content of uterine tissues was greater in EB-, EB+P-, and EB+P+EB-treated gilts than in their respective controls, and this response was augmented by RLX in all treatment groups. Administration of steroids stimulated a 4- to 5-fold increase in uterine dry weight compared to that in controls, with responses not differing between EB+P- and EB+P+EB-treated gilts. In all groups, RLX increased uterine dry weight. Protein and DNA contents of uterine tissue increased with steroid treatment, but neither variable differed between EB+P- and EB+P+EB-treated gilts. Administration of RLX, alone or in combination with steroids, increased protein and DNA contents of uterine tissues. The tissue content of GAGs increased in response to steroids, and coadministration of RLX did not alter this response. Although the uterine tissue concentration of collagen was reduced in steroid- and RLX-treated gilts, the collagen content of the uterus was not affected by the various treatments. The results of this study indicate that RLX is a potent stimulator of uterine growth under a variety of steroidal environments. RLX- or steroid-induced uterine growth was manifest by increased water, dry matter, protein, and DNA and GAG contents, but the uterine content of collagen was not affected. The overall growth-promoting effects of EB and the stimulation of DNA accretion by RLX were not observed when gilts were cotreated with P.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597135 TI - Dietary potassium supplementation and sodium restriction stimulate aldosterone synthase but not 11 beta-hydroxylase P-450 messenger ribonucleic acid accumulation in rat adrenals and require angiotensin II production. AB - Increasing evidence indicates that the adrenal cortex of most mammalian species expresses distinct forms of cytochrome P-450(11 beta), a steroidogenic enzyme that catalyses the terminal steps in the biosynthesis of both glucocorticoids and mineralocorticoids. In the human, mouse, and rat, two genes have been isolated, designated CYP11B1 and CYP11B2. The product of CYP11B2 (aldosterone synthase) is required for the successive 11 beta-, 18-hydroxylations and 18-oxidation of deoxycorticosterone that lead to the production of aldosterone in the zona glomerulosa. In contrast, the product of CYP11B1 (11 beta-hydroxylase) mediates only the 11 beta-hydroxylation of deoxycorticosterone and 11-deoxycortisol. The recent identification of these two P-450(11 beta) isozymes mandates further analysis of their expression in different zones of the adrenal cortex, both under basal conditions and in response to conditions known to alter mineralocorticoid biosynthesis. To evaluate the expression of the two isozymes in different adrenocortical zones, we performed Northern blotting analyses with specific oligonucleotide probes that discriminated between the two forms of rat P-450(11 beta). The transcripts detected by the two probes were of similar size (2.7 kilobase), but differed in their zonal distribution: aldosterone synthase P-450 messenger RNA (mRNA) was detected only in zona glomerulosa, whereas 11 beta hydroxylase P-450 was expressed in both zona fasciculata-reticularis and zona glomerulosa. Next, we analyzed the response of these two genes to various physiological and pharmacological interventions known to affect aldosterone biosynthesis. High potassium or low sodium diet given to rats for 1 week increased aldosterone synthase P-450 mRNA levels by approximately 5- and 6-fold, respectively. These increases, moreover, were significantly attenuated by treatment with captopril, an inhibitor of angiotensin-converting enzyme. In contrast, neither dietary manipulation significantly affected 11 beta-hydroxylase P-450 mRNA levels in any zone. Thus, stimulation of the terminal steps of aldosterone biosynthesis by variations in dietary intake of monovalent cations involves regulation of aldosterone synthase P-450 mRNA levels. Finally, captopril inhibited potassium induction of aldosterone synthase P-450 mRNA levels despite the presence of low plasma renin activity in the potassium-treated rats. This finding implicates intraadrenal angiotensin II formation in the effect of potassium on mineralocorticoid production. PMID- 1597137 TI - Lactotrophs secreting small amounts of prolactin reveal great responsiveness to thyrotropin-releasing hormone: analysis by the sequential cell immunoblot assay. AB - The effects of TRH on PRL secretion from individual lactotrophs of female rats were investigated by using a sequential cell immunoblot assay. The same pituitary cells cultured on coverslips were first incubated to determine basal secretion of PRL and subsequently challenged by one of various concentrations of TRH. The PRL secreted from the single lactotrophs was absorbed on protein-blotting transfer membranes, immunostained, and quantified by microscopic image analysis. When no TRH was added to the medium used in the second incubation (controls), the amount of PRL secreted from individual lactotrophs was 93% of that secreted in the first incubation. Treatment with 3 x 10(-10)-10(-7) M TRH in the second incubation increased in a dose-dependent manner the proportion of lactotrophs whose PRL secretion was significantly greater than confidence limits for PRL secretion in the controls. However, the percentage of TRH-responsive lactotrophs remained less than 50% even at a maximally effective concentration of TRH. Proportions of the TRH-responsive lactotrophs were significantly greater in cells that secreted small amounts of PRL under basal conditions than in those that secreted large amounts. Furthermore, the small, but not the large, secretors showed a significant increase in mean absolute amounts of PRL secreted by 10(-7) M TRH, which represented no less than 45% of all PRL secreted from the lactotroph population by the TRH treatment. These results indicate that 1) there is a heterogeneity with respect to lactotroph responsiveness to TRH and that 2) a population of lactotrophs that secrete small amounts of PRL under basal conditions contains a much larger proportion of TRH-responsive lactotrophs than does a population of lactotrophs that secrete large amounts of PRL. PMID- 1597138 TI - Expression of diazepam binding inhibitor-like immunoreactivity in rat testis is dependent on pituitary hormones. AB - Diazepam binding inhibitor-like immunoreactivity (DBI-LI) in normal and hypophysectomized (HPX) rat testis was studied by light and electron microscopic immunohistochemistry. In normal testis DBI-LI was observed in interstitial Leydig cells and Sertoli cells of most seminiferous tubules. At the electron microscopic level, DBI-LI was distributed throughout the cytoplasm of labeled cells; a concentration of the labeling product was observed in the smooth endoplasmic reticulum, Golgi apparati, and the outer membrane of the mitochondria. In the seminiferous epithelium, labeled processes of Sertoli cells could be traced among developing germ cells. After HPX a gradual disappearance of DBI-LI was observed in all Leydig cells. The number of labeled Sertoli cells was reduced in the majority of tubules after HPX, whereas in some tubules the staining was only slightly reduced. Replacement therapy of the HPX animals with human CG prevented the disappearance of DBI-LI from Leydig cells, whereas replacement with FSH did not prevent the disappearance of DBI-LI in Leydig cells. In Sertoli cells replacement therapies were not effective in restoring DBI-LI. In rat testis DBI and mitochondrial benzodiazepine binding sites are highly concentrated in the Leydig cells. Mitochondrial benzodiazepine binding sites and DBI are involved in the regulation of steroid production. As the expression of DBI-LI is under the control of pituitary hormones, DBI may play a role as an endogenous regulator of intracellular metabolic functions, such as steroidogenesis, in rat testis. PMID- 1597140 TI - Exogenously administered testosterone maintains spermatogenesis quantitatively in adult rats actively immunized against gonadotropin-releasing hormone. AB - The administration of testosterone via Silastic capsules has been shown previously to maintain advanced spermatid number quantitatively in intact rats in which LH but not FSH was suppressed, but not in hypophysectomized rats, indicating that pituitary factors in addition to LH are required for the quantitative maintenance of spermatogenesis in the rat. The objective of the present study was to examine whether testosterone is capable of maintaining quantitatively normal spermatogenesis in rats in which both LH and FSH are suppressed. Intact adult male rats were actively immunized against GnRH by intradermal injection of GnRH conjugated to human serum globulin; control rats received intradermal injections of saline and adjuvant. Four weeks after the primary immunization, GnRH-immunized rats received the first booster injection and, at the same time, received testosterone-filled polydimethylsiloxane (PDS) implants of 4, 8, 12, or 24 cm or empty implants. Booster injections were repeated every 2 weeks for 8 weeks. At that time, rats were killed, and serum levels of LH, FSH, and testosterone, testicular advanced spermatid number, and seminiferous tubule fluid testosterone concentrations were determined. Four weeks after the initial administration of GnRH immunogen, i.e. before the first booster injection, serum levels of testosterone, LH, and FSH and the number of advanced spermatids per testis were not different from those in controls. Eight weeks after the first booster injection, serum LH and FSH and advanced spermatids were undetectable in all GnRH-immunized rats. The administration of testosterone filled PDS implants of 4 and 8 cm to GnRH-immunized rats for 8 weeks resulted in the maintenance of 105 +/- 6 and 161 +/- 5 x 10(6) advanced spermatid/testis, respectively, significantly less than the control value (237 +/- 19 x 10(6)). In GnRH-immunized rats that received testosterone-filled PDS implants of 12 or 24 cm, the advanced spermatid numbers per testis (228 +/- 4 and 229 +/- 8 x 10(6), respectively) were not significantly different from those in controls. These results indicate that testosterone is capable of maintaining spermatogenesis quantitatively in the adult rats testis, in the absence of both radioimmunoassayable LH and FSH. PMID- 1597139 TI - The low molecular weight heat shock protein (hsp27) in rat Sertoli cells: evidence for identity of hsp27 with a germ cell-responsive phosphoprotein. AB - The low mol wt heat shock protein (hsp27) exists as three forms. hsp27a is the most basic and is not phosphorylated. The other two forms are phosphorylated, with hsp27b of intermediate isoelectric point and hsp27c as the most acidic form. We hypothesized that a Sertoli cell protein, previously discovered as being responsive to germ cells and referred to as GC1, is hsp27c. To investigate this hypothesis, cultured Sertoli cells were treated with CdCl2 or were heat shocked and then labeled with H3(32)PO4, [35S]methionine, or 3H-labeled amino acids. Sertoli cell proteins were then prepared for two-dimensional polyacrylamide gel electrophoresis and autoradiography or fluorography. The 27K protein did not incorporate [35S] methionine. After CdCl2 or heat shock treatments, hsp27b and hsp27c (GC1) showed increasing 32P incorporation with time. To test if this result was due to increased synthesis of hsp27 Sertoli cell proteins were labeled with 3H-labeled amino acids. Heat shock and CdCl2 resulted in time-dependent increases in 3H label incorporation into all three forms of hsp27. Shortly after heat shock, a greater proportion of hsp27b and hsp27c was observed in the pellet fraction of Sertoli cell homogenates, with more of these hsp27 forms being found in the supernatant fraction after 4 h recovery from heat shock. Treatment of CdCl2-exposed Sertoli cells with germ cells increased 32P labeling of hsp27c (GC1). The location on two-dimensional gels of the most acidic form of hsp27, hsp27c, was exactly coincident with the location of GC1. Taken together, the results support the conclusion that GC1 in Sertoli cells is hsp27c. PMID- 1597141 TI - Steroids can modulate transdifferentiation of prolactin and growth hormone cells in bovine pituitary cultures. AB - Fluctuations in the proportions of pituitary acidophils (cells that release GH and PRL, either separately or concurrently) have been correlated with dynamic changes in the steroid hormone milieu. Since modulation of these acidophilic subtypes can occur without appreciable alterations in the total number of acidophils, it has been proposed that GH- and PRL-secreting cells can actually transdifferentiate (gain or lose the ability to release GH or PRL). To test this hypothesis, we examined the effects of steroids on the proportions of cells that released GH, PRL, or both hormones (i.e. mammosomatotropes) in bovine pituitary cell cultures. Specifically, anterior pituitary cells from castrated males were cultured for 6 days in the absence (controls) or presence of 17 beta-estradiol, cortisol, or progesterone. Reverse hemolytic plaque assays revealed that 6.64 +/- 1.2% of all pituitary cells released GH, while 68.8 +/- 5.3% were PRL secretors in control cultures. Cortisol and progesterone induced an increment in the proportions of GH-secreting cells (10 nM cortisol, +11.7 +/- 2.4%; 1000 nM cortisol, +10.5 +/- 4.7%; 1000 nM progesterone, +2.87 +/- 1.5%) above control values while decreasing the relative abundance of cells that released PRL (10 nM cortisol, -7.6 +/- 1.7%; 1000 nM cortisol, -6.6 +/- 1.2%; 1000 nM progesterone, 5.5 +/- 1.3%) below control values. However, 17 beta-estradiol was ineffective in this regard at doses of 0.1-1000 nM. A more critical examination of the steroid induced changes revealed that they were attributable to increases in the proportions of cells that released GH alone and both hormones simultaneously along with a concomitant decrease in the fraction that secreted only PRL. Two lines of evidence discount the possibility that these effects were due to selective cell proliferation. First, the mitotic rate of cultures (assessed by immunofluorescent detection of bromodeoxyuridine incorporation) was only about 1% of all cells in both control and steroid-treated cultures. Second, blocking cell proliferation by the addition of cytosine arabinoside (100 microM) did not inhibit the cortisol-induced augmentation of GH-releasing cells. Taken together, these results substantiate the hypothesis that acidophilic subpopulations are capable of transdifferentiation given an appropriate hormonal signal. PMID- 1597142 TI - Age-related alterations in calbindin-D28K induction by 1,25-dihydroxyvitamin D3 in primary cultures of rat renal tubule cells. AB - In vivo studies have indicated that renal calbindin-D28K protein and mRNA levels decrease in adult and old rats, and this decrease parallels the age-associated decline in serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] levels. However, diminished renal responsiveness to 1,25-(OH)2D3 with advancing age could also contribute to decreased calbindin-D28K expression. To study renal responsiveness with age, primary cell cultures were established from the kidney cortices of young (1 month old), adult (10-12 months old), and old (20-24 months old) rats. Cells were incubated in medium K-1 containing 2% fetal calf serum. Calbindin-D28K protein levels were determined by Western blot and enzyme-linked immunosorbent assay. In young animals, the levels of calbindin-D28K declined from 12.1 +/- 1.3 micrograms/mg protein in the intact kidney to 1.6 +/- 0.07 micrograms/mg protein in cells that had been cultured for 3 days in the absence of 1,25-(OH)2D3. This sharp decline in calbindin-D28K protein concentration moderated by days 6-8. The continuous presence of 10(-7) M 1,25-(OH)2D3 in the medium did not abolish the decline. The low levels of calbindin-D28K in the cells cultured in the absence of 1,25-(OH)2D3 provided an excellent experimental system in which to compare the response of the cells to 1,25-(OH)2D3 between age groups. In cultured cells treated with 1,25-(OH)2D3 for 72 h, calbindin-D28K induction was greater in cells from adult and old animals compared to cells from young animals. The ratios of calbindin-D28K content (with vitamin D/without vitamin D) were 2.2 +/- 0.2, 4.7 +/- 0.5, and 7.1 +/- 1.5 for young, adult, and old cells, respectively. These studies suggested that the observed in vivo decrease in renal calbindin-D28K with age is primarily due to the lowered circulating 1,25-(OH)2D3. PMID- 1597143 TI - Roles of interleukin-1 alpha and -1 beta in endotoxin-induced suppression of plasma gonadotropin levels in rats. AB - Using specific antagonists to rat interleukin (IL)-1 alpha and IL-1 beta, the roles of these IL-1s in endotoxin-induced suppression of plasma gonadotropin levels in freely-moving rats were studied. In orchiectomized rats, recombinant rat IL-1 alpha and IL-1 beta administered into the lateral ventricles almost equipotently suppressed plasma LH levels. Twenty five micrograms of bacterial endotoxin or lipopolysaccharide (LPS) administered similarly showed a comparable effect as that of 1 microgram IL-1 alpha or IL-1 beta, and completely lowered plasma LH levels by 60 min after the injection. To examine the roles of endogenous IL-1 alpha and IL-1 beta, anti-rat IL-1 alpha antiserum (anti-IL-1 alpha) and a recombinant human IL-1 receptor antagonist (IL-1ra) were used as specific blockers for IL-1 alpha and IL-1 beta, respectively. Anti-IL-1 alpha (10 microliters) or IL-1ra (10 micrograms) administered intracerebroventricularly (icv) with 25 micrograms LPS, significantly attenuated the LPS-induced effect on plasma LH levels during the first 60 min after LPS infusion, but not during the second 60 min. LPS at a dose of 5 micrograms induced smaller but still significant changes in plasma LH levels compared with 25 micrograms LPS or 1 microgram IL-1 beta. IL-1ra (10 micrograms) completely blocked LH suppression induced by 1 microgram IL-1 beta, but did not completely reverse the changes of LH induced by 5 micrograms LPS. IL-1ra injected iv also significantly attenuated the early suppressive effect of iv administered LPS, but not its late effect on plasma LH levels. However, iv administered IL-1ra had no influence on the effects of icv administered LPS. These data indicate that at least a part of plasma LH suppression caused by icv administered LPS is mediated via IL-1 alpha and IL-1 beta synthesized within the brain, while factor(s) other than IL-1 also participate in the LPS-induced change, particularly during the later period. A similar mechanism may also work peripherally in the case of iv administered LPS induced plasma LH suppression. PMID- 1597144 TI - Solubilization of the receptors for avian pancreatic polypeptide in chicken, canine, and pig brains. AB - When n-octyl-beta-D-glucoside was used in several detergents to extract active avian pancreatic polypeptide (APP) receptors, a specific binding of [125I]APP to the solubilized chicken cerebellar and porcine hippocampal membranes was found. The binding of [125I]APP to the solubilized receptors was dependent on incubation time, temperature, and protein concentrations and appeared to have a slightly acidic optimal pH. APP binding to chicken and porcine brain extracts showed a high specificity for APP, although the chicken receptors do not discriminate well between APP and its related peptides, neuropeptide Y and peptide YY. Scatchard analyses of competitive binding data indicated the presence of two classes of binding sites in the brain extracts as in membrane-bound receptors; however, the high affinity component of the chicken receptor showed a decreased affinity after extraction. APP receptors in chicken and porcine brain extracts retained their insensitivity to the nonhydrolyzable GTP analog guanosine 5'-O-(3 thiotriphosphate). Cross-linking studies were performed with the homobifunctional cross-linker disuccinimidyl suberate and brain membrane receptors solubilized with n-octyl-beta-D-glucoside. An APP receptor species with a M(r) of 67,000, the same size as that of the labeled protein in native membrane homogenates of chicken and pig brains, was identified. However, in the canine brain we observed a M(r) 85,000 receptor protein, suggesting that species differences exist among the structures of brain APP receptors. The solubilized cross-linked APP receptors in these species were adsorbed by wheat germ agglutinin-agarose and by concanavalin A, indicating that they are glycoprotein in nature. The availability of the solubilized receptors from vertebrate brains with n-octyl-beta-D-glucoside represents an important step toward the purification and molecular characterization of the APP receptors. PMID- 1597145 TI - Testosterone suppresses 8-bromo-adenosine 3',5'-monophosphate and gonadotropin releasing hormone-stimulated luteinizing hormone subunit synthesis. AB - The major objective of this study was to determine the effects of testosterone (T) on 8-bromo-cAMP (8-br-cAMP)- and GnRH-stimulated LH subunit polypeptide synthesis and glycosylation in cultured male anterior pituitary cells. The anterior pituitaries from 1-week castrate male rats were enzymatically dispersed and incubated for 48 h in steroid-free medium, followed by a 48-h incubation with or without 10 nM T. The cells were then incubated for 12 h in medium containing [35S]methionine ([35S]Met) and [3H]glucosamine ([3H]Gln) with or without 1 mM 8 br-cAMP or 1 nM GnRH, with or without 10 nM T. Incorporation of radiolabeled precursors into LH subunits was determined by specific immunoprecipitation of the LH dimer with subsequent analysis of the individual LH alpha- and beta-subunits by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. LH content was quantified by RIA (iLH). Both 8-br-cAMP and GnRH stimulated iLH release. T suppressed basal and GnRH-induced iLH secretion, whereas it enhanced iLH release stimulated by 8-br-cAMP. Both 8-br-cAMP and GnRH stimulated total (cell plus medium) [35S]Met and [3H]Gln incorporation into LH alpha and LH beta, and these responses were suppressed by T. Basal [35S]Met incorporation into the LH subunits was inhibited by T, whereas T had no effect on basal levels of [3H]Gln incorporation. Neither T nor GnRH altered [3H]Gln cell uptake or incorporation into total proteins, whereas 8-br-cAMP increased these responses. There were no treatment effects on [35S]Met cell uptake or incorporation into total proteins. These results suggest that 8-br-cAMP, similar to GnRH, stimulates both polypeptide synthesis and glycosylation of the LH alpha- and beta-subunits and that T suppresses these responses to 8-br-cAMP and GnRH in a similar fashion. These data indicate that cAMP is involved in mediating the actions of GnRH on LH subunit biosynthesis and that the inhibition of LH subunit polypeptide synthesis and glycosylation by T involves postreceptor events that are regulated by cAMP dependent mechanisms. PMID- 1597146 TI - Effects of insulin on diacylglycerol/protein kinase-C signalling and glucose transport in rat skeletal muscles in vivo and in vitro. AB - Insulin treatment in vivo provoked rapid dose-related increases in diacylglycerol content and/or translocation of protein kinase-C (PKC) from cytosol to membranes in rat soleus and gastrocnemius muscles. These effects were apparent with 1) insulin doses that provoked submaximal and maximal increases in glucose utilization, and 2) glucose-stimulated endogenous insulin secretion. Insulin stimulated PKC translocation was evident when PKC was assayed by 1) histone or protamine phosphorylation after PKC purification by Mono Q column chromatography, and 2) immunoblotting for PKC beta and PKC epsilon. Dose-related effects of insulin on PKC translocation were also observed in the rat soleus in vitro, and this was associated with increased phosphorylation of 40- and 80-kilodalton proteins, which were also phosphorylated by phorbol ester treatment. A role for diacylglycerol-PKC signalling in insulin-stimulated glucose transport was suggested by studies of [3H]2-deoxyglucose ([3H]2-DOG) uptake in the rat soleus in vitro in that 1) PKC translocation and 2-DOG uptake were correlated; and 2) stimulatory effects of insulin and phorbol esters on 2-DOG uptake were apparently nonadditive. PMID- 1597147 TI - Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver. AB - Apolipoprotein-B 48 (apoB 48) and apoB 100 expression and the editing of apoB mRNA have previously been shown to be hormonally regulated in rat liver. We have investigated the effects of hypophysectomy and replacement therapy with T4, cortisol (C), and GH in vivo on the proportion of edited apoB mRNA in rat liver and cultured rat hepatocytes as well as the synthesis and secretion of apoB 48 and apoB 100 in cultured rat hepatocytes. Hypophysectomy decreased the proportion of edited apoB mRNA in intact liver from 62% in normal rats to 29% in hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C did not influence the proportion of edited apoB mRNA, whereas treatment with GH, either alone or together with T4 and C, increased the proportion of edited apoB mRNA to the levels observed in normal rats. In cultured hepatocytes isolated from normal rats, the proportion of apoB 48 (percentage of total labeled apoB) was 78% and decreased to 40% in cells isolated from hypophysectomized rats. Treatment of hypophysectomized rats with T4 and C had no effect on the proportion of apoB 48 present in isolated cells, whereas it increased to 60% after treatment with GH together with T4 and C. The proportion of apoB 48 in the medium was affected by hypophysectomy and the various hormonal treatments in a similar way to that observed in the cells. Results from in vivo labeling experiments suggested that GH alone had the capacity to increase the percentage of apoB 48 in hypophysectomized rats. On the contrary, T4 and C was needed, in addition to GH, to increase the proportion of apoB 48 in isolated hepatocytes from hypophysectomized rats. Our results suggest that this discrepancy is due to a difference between the effect of GH alone on apoB mRNA editing in the intact liver and that in isolated hepatocytes. The total secretion of apoB into the cell culture medium was not affected by hypophysectomy and hormonal treatments of the rats. In conclusion, these results indicate that GH is involved in the regulation of editing of apoB mRNA and the proportion of apoB 48 synthesized and secreted in rat liver. Thus, our observations emphasize the importance of GH as a regulator of lipoprotein metabolism. PMID- 1597148 TI - Changes in molecular variants during in vitro transformation and release of prolactin by the pituitary gland of the lactating rat. AB - PRL transformation involves a dopamine (DA)-controlled, thiol-mediated decrease in pituitary PRL detectability that precedes and may determine increased PRL release. The present studies were designed to determine 1) whether structural changes occur to adenohypophyseal (AP) PRL during in vitro transformation and may account for decreased PRL detectability; 2) whether such changes occur within AP PRL granules; 3) the type and proportion of secreted PRL variants; and 4) the influence of DA and/or thiol reducing agents upon AP PRL molecular changes. Quartered APs of 8 h nonsuckled lactating rats, injected or not with [3H]leucine (5 mCi/g body wt, 8 h before death) were incubated for 30-240 min. The effects of DA (50 microM) with or without reduced glutathione (10 mM), and the alkylant N ethylmaleimide (1 mM) were compared to the changes in PRL molecular variants occurring in control incubated AP fragments. Polyacrylamide gel electrophoresis (PAGE) under native conditions and sodium dodecyl sulfate (SDS)-PAGE under reducing (R) or nonreducing (NR) conditions were used to resolve molecular variants of PRL and [3H]PRL, followed by Western blotting and densitometric/liquid scintillation techniques, respectively. Up to 5 and 10 major forms of immunoreactive PRL were resolved by PAGE and SDS-PAGE, respectively. The spontaneous transformation after 30 min incubation was correlated with a decrease of 23K PRL and 23K [3H]PRL bands and an increase in high mol wt (80 to greater than 100K) PRL forms. These changes were reversible upon reduction of the proteins before electrophoresis or after extraction of preparative gels. DA and N ethylmaleimide prevented, whereas reduced glutathione induced these changes. Similar changes were observed in isolated granules from nonincubated and incubated pituitary fragments. Secreted PRL was also polymorphic, with a high predominance of 23K PRL and 23K [3H]PRL. In addition, a polymeric PRL variant, which in reducing gels showed an apparent mol wt of 27K, was secreted in high proportion, similar to that of 23K PRL. The nature of this polymeric variant of PRL is unclear at present. Altogether, these results suggest that a dynamic interconversion of PRL molecular variants occur during transformation. The decreased detectability associated with PRL transformation appears to involve the association of 23K PRL molecules into a 80 to greater than 100K disulfide-linked oligomer. This association is reversible upon reduction and takes place within secretory granules. DA appears to inhibit PRL transformation by preventing thiol disulfide interchange. PMID- 1597149 TI - Development of Cushing's syndrome in corticotropin-releasing factor transgenic mice. AB - CRF is released in response to various stressors and regulates ACTH secretion and glucocorticoid production. CRF overproduction has been implicated in affective disorders, such as depression and anorexia nervosa, and may lead to Cushing's syndrome. To test whether CRF overproduction leads to Cushing's syndrome and to develop an animal model of chronic pituitary-adrenal activation, the CRF gene was expressed under control of the metallothionein promoter in transgenic mice. CRF transgenic animals exhibit endocrine abnormalities involving the hypothalamic pituitary-adrenal axis, such as elevated plasma levels of ACTH and glucocorticoids. These animals display physical changes similar to those of patients with Cushing's syndrome, such as excess fat accumulation, muscle atrophy, thin skin, and alopecia. These findings indicate that chronic production of excess CRF results in sustained stimulation of pituitary corticotrope cells, resulting in elevated ACTH and consequent glucocorticoid overproduction, a condition that leads to the development of Cushing's syndrome. Analysis of CRF mRNA distribution revealed that transgene expression is primarily restricted to cells that express the endogenous CRF gene and does not follow the pattern predicted of a metallothionein-regulated gene. These results suggest that DNA elements located outside of the CRF promoter but present within the CRF intron, coding, or 3'-flanking regions may contribute to the cell type specificity of CRF gene expression. PMID- 1597150 TI - Voltage-dependent calcium current in human decidual cells and its relation to prolactin secretion. AB - Human decidual cells synthesize and release decidual PRL (dPRL) immunologically and biochemically identical to human pituitary PRL. However, stimulators and inhibitors of PRL secretion such as TRH, bromocriptine or dopamine have no effect on dPRL release. The evidence for the involvement of Ca2+ in dPRL release is based on contradictory or unclear data. Since little is known about Ca2+ movement in human decidual cells we studied the membrane Ca2+ conductance of cultured decidual cells using the patch-clamp technique in the whole-cell configuration. We report the existence of Ca(2+)-dependent action potentials triggered by hyperpolarizing or depolarizing pulses and blocked by cobalt (Co2+; 5 mM). Spontaneous action potentials were observed in the cell-attached mode and found also to be Co(2+)-sensitive. A tetrodotoxin-insensitive and Ca(2+)-dependent rapidly inactivating inward current was investigated in voltage clamp. Its activation threshold was between -60 and -45 mV. Indo-1 measurements of free intracellular Ca2+ concentrations ([Ca2+]i, 169 +/- 14 nM and 141 +/- 8 nM in short-term culture vs. 149 +/- 5 nM in cells cultured for 3-6 days) showed that decidual cells have spontaneous transient fluctuations of [Ca2+]i and that [Ca2+]i was decreased by Ca2+ channel blockers. The existence of Ca2+ movements in decidual cells in culture is thus demonstrated. The occurrence of action potentials in decidual cells derived from fibroblasts, reputed to be inexitable cells, is an interesting biological observation. However, Ca2+ is not involved in the short-term release of PRL by decidual cells, and its effects on long-term secretion still requires further investigation. PMID- 1597151 TI - Gonadotropin-releasing hormone-stimulated intracellular Ca2+ fluctuations and luteinizing hormone release can be uncoupled from inositol phosphate production. AB - In order to study the dependence of GnRH-stimulated LH release on inositol phosphate (IP) turnover, this study used an inhibitor of phospholipase C activity, 1-[6-[[17 beta-3- methoxyestra-1,3,5(10)-triene-17-yl]amino]hexyl]-1H pyrrole-dione (U-73122) and an inactive analog 1-[6[[17 beta-3-methoxyestra 1,3,5(10)- triene-17-yl]amino]hexyl]2,5-pyrrolidine-dione (U-73343). U-73122 (10 microM) decreased GnRH-provoked (1 microM, 45 min) IP accumulation from 873 +/- 61 dpm to 365 +/- 50 dpm (basal accumulation also was decreased from 420 +/- 18 dpm to 207 +/- 16 dpm) while LH release was not inhibited (30.2 +/- 1.4% of cellular LH in control compared to 30.3 +/- 1.1% in U-73122 pretreated cells). GnRH provoked increased IP3 accumulation (123% of basal) after 15 sec of stimulation, IP2 accumulation (131% of basal) after 30 sec, and IP1 (121% of basal) after 1 min. Pretreatment with U-73122 blocked accumulation of IPs at these early timepoints. Sodium fluoride (NaF)-stimulated IP accumulation was also inhibited by U-73122 (from 1539 +/- 132 dpm to 414 +/- 21 dpm) while LH release increased from 22.9 +/- 1.4% total cellular LH to 28.0 +/- 2.2%. In contrast, GnRH- and NaF-stimulated IP accumulation were not significantly decreased in U 73343 pretreated cells (GnRH: 817 +/- 43 dpm compared to 873 +/- 61 dpm in control; NaF: 1133 +/- 74 dpm compared to 1539 +/- 132 dpm in control cells). Results of a perifusion study showed that U-73122 did not block the initial phase of GnRH-stimulated LH release or interfere with the development of desensitization to the releasing hormone. In addition, GnRH-stimulated intracellular Ca2+ fluctuations were similar in magnitude and duration in U-73122 pretreated compared to U-73343-pretreated cells. These results demonstrate that GnRH- as well as NaF-stimulated LH release can be uncoupled from IP production calling to question the role of IP3 as a second messenger for GnRH-stimulated LH release. PMID- 1597152 TI - Prolactin and secretogranin-II, a marker for the regulated pathway, are secreted in parallel by pituitary GH4C1 cells. AB - The granins are a family of tyrosine-sulfated secretory proteins. Two members of this family, chromogranin-B (CgB) and secretogranin-II (SgII), are found in GH4C1 cells, a pituitary cell line that secretes PRL and GH. We have compared the spontaneous and regulated secretion of CgB and SgII with that of PRL in GH4C1 cells and have assessed the importance of granin sulfation on granin and PRL processing and secretion. CgB and SgII were identified by metabolic labeling with [35S]SO4, which was predominantly incorporated into two bands of 105,000 (CgB) and 84,000 (SgII) mol wt. The secretion of [35S]SgII and [35S]PRL from GH4C1 cells simultaneously labeled with 35S-labeled SO4 and methionine showed similar kinetics over 60 min, suggesting that the two proteins are similarly processed. CgB, SgII, and PRL were released in parallel after 10-min treatment with secretagogues (high K+ and BAY K8644, 8-bromo-cAMP, a phorbol ester, and TRH). Hypertonicity and substitution of chloride with isethionate, which inhibit stimulated PRL release, reduced the amount of CgB and SgII released in response to secretagogues, but not basally. Cells were labeled with [35S]SO4 with or without 10 mM chlorate, which inhibits sulfation by more than 90%, and media and cells were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, autoradiography, and immunoblotting using an antibody directed against the N terminus of SgII. Chlorate reduced [35S]SO4 labeling of CgB and SgII, but had little effect on immunoreactive SgII in cells or media. Inhibiting sulfation with chlorate did not change the amount of PRL or GH synthesized and secreted by GH4C1 cells, basally or in response to secretagogues, or the induction of PRL storage by insulin, estrogen, and epidermal growth factor. The results show that granins are released from GH4C1 cells in parallel with GH and PRL under basal and stimulated conditions, and that sulfation is not essential for normal packaging and processing of these secretory proteins. The data suggest a model in which PRL, CgB, and SgII are sorted to the regulated pathway and released from this pathway basally as well as under stimulated conditions. PMID- 1597153 TI - Transcriptional and posttranscriptional regulation of the proopiomelanocortin gene in the pars intermedia of the pituitary gland of Xenopus laevis. AB - In the melanotrope cells of the intermediate pituitary gland of the amphibian Xenopus laevis, expression of the POMC gene is under physiological control, i.e. it is 20- to 30-fold higher in animals adapted to a black background compared to animals adapted to a white background. To investigate whether changes in POMC messenger RNA stability contribute to this difference in expression, a steady state kinetic model for mRNA degradation was used to determine the half-life of POMC mRNA during the induction and deinduction of POMC gene expression in melanotrope cells. During induction of the POMC gene the half-life of POMC mRNA was 3- to 4-fold longer than during deinduction. This difference in mRNA stability is, however, not sufficient to account for the 20- to 30-fold difference in the steady state levels of POMC mRNA between the two physiological conditions. Results from experiments with the protein synthesis inhibitor cycloheximide and the mRNA synthesis inhibitor 5,6-dichloro-1-beta-D ribofuranosylbenzidimidazole suggest 1) that during induction of POMC gene expression no de novo protein synthesis is required and, 2) that deinduction of POMC gene expression requires transcriptional activation of an mRNA-degradation system. Pulse-labeling experiments with [3H]uridine showed that in neurointermediate lobes of white-adapted animals there is an 8-fold higher amount of newly synthesized POMC mRNA than in lobes of black animals. This suggests a fast in vitro induction of POMC gene transcription. The dopamine D2-receptor agonist apomorphine decreased POMC mRNA biosynthesis about 5-fold, which confirms that regulation of POMC gene expression includes a transcriptional component. In conclusion, our results demonstrate that during the physiological process of background adaptation the regulation of POMC gene expression in Xenopus melanotrope cells is exerted by alterations in POMC gene transcription as well as in POMC mRNA stability. PMID- 1597154 TI - The unliganded glucocorticoid receptor is localized in the nucleus, not in the cytoplasm. AB - The glucocorticoid receptor (GR) is often described to be localized in the cytoplasm in the absence of hormone and to translocate to the nucleus upon binding of the hormone. This apparently different behavior of the GR compared to that of other members of the steroid receptor superfamily is unexpected because similarities in the molecular structures of steroid hormone receptors would predict similarities in their working mechanisms. The absence of the unliganded GR from the nuclear compartment may be due to an artefactual redistribution, occurring during the immunocytochemical procedure. We systematically studied the effects of various fixation and permeabilization procedures on the distribution of the GR in hepatoma cells that were incubated in steroid-free or steroid containing medium. Immunofluorescent labeling of the GR in formaldehyde-fixed and detergent-permeabilized cells resulted in the almost complete absence of immunoreactivity of cells when the receptor was in its unliganded form, whereas the liganded receptor was detected mainly in the nucleus. On the other hand, labeling of cryosectioned glutaraldehyde/formaldehyde-fixed cells demonstrated that receptor antigenicity is present in the nucleus in the absence as well as the presence of steroid. We conclude that the results obtained with the cryosectioning procedure reflect the receptor distribution in the living cell, since glutaraldehyde fixation of the cells prevented the washout of loosely bound receptor. The predominantly nuclear location of the unliganded GR in hepatoma cells and the absence of changes in distribution after steroid stimulation imply that the nuclear translocation model is not true for the GR. PMID- 1597156 TI - Ubiquitous distribution of growth hormone receptors and/or binding proteins in adenohypophyseal tissue. AB - Liver GH receptor (GHR)-like mRNA has been shown to be widely distributed throughout rat and rabbit pituitary glands. In the present study RNA extracted from rabbit anterior pituitary glands was reverse transcribed, and the cDNA amplified by the polymerase chain reaction (PCR) in the presence of 3'- and 5' flanking oligonucleotide primers for the extracellular and transmembrane domains of the rabbit GHR. A 499-basepair (bp) fragment was generated, identical in size to that in rabbit liver, kidney, and adipose tissue. Digestion of this fragment with a restriction endonuclease (SalI) produced moieties of 280 and 219 bp, as observed for the amplified cDNA fragments from liver, kidney, and adipose tissue. In situ hybridization of a cRNA probe for the rabbit GHR with cryostat sections of the anterior pituitary gland was demonstrated. Specific hybridization occurred throughout the adenohypophysis and was present in somatotroph and nonsomatotroph cells, identified by hybridization of the same tissue sections with a complementary riboprobe for rat GH mRNA. Electron microscopy and immunogold staining, using monoclonal antibodies against the extracellular domain of the rat (MAb 263) or rabbit (MAb 7) GHR, demonstrated the presence of the receptor or binding protein throughout rat and rabbit anterior pituitary gland. Immunostaining occurred in somatotroph and nonsomatotroph cells and was widely distributed throughout the intracellular and nuclear compartments. In GH secreting cells gold particles were specifically accumulated in the secretory granules and heterochromatin, but were also present in mitochondria, Golgi, endoplasmic reticulum, cytoplasm, nucleoplasm, and cellular and nuclear membranes. A similar distribution of GHR immunoreactivity was observed within rat and rabbit hepatocytes. Specific binding sites for radiolabeled ovine GH to cytosolic fractions and to crude solubilized preparations of plasma and nuclear membranes of the rat anterior pituitary gland were also demonstrated. The binding of the tracer to these sites was inhibited by prior exposure to MAb 263, which binds to epitopes in the ligand-binding domain of the rat GHR. These results provide evidence of 1) the expression and translation of the GHR gene in rat and rabbit adenohypophysis in 2) GH and non-GH-secreting cells, and 3) the presence of GH receptors/binding proteins throughout the intracellular and nuclear compartments of these cells. PMID- 1597155 TI - Peripheral and not central suppression of ovarian function during osmotic pump infusion of adrenocorticotropin-(1-24) for one menstrual cycle in the cynomolgus monkey and its partial compensation by a transitory elevation of sex hormone binding globulin levels. AB - The purpose of our study was to assess the impact of subchronic administration of ACTH-(1-24) on ovarian function in the primate using a repeated measures experimental design. Osmotic pumps that released ACTH-(1-24) at a dose of 67 micrograms/day were implanted sc in four cynomolgus monkeys for one menstrual cycle. The pumps were filled with saline for the two control cycles, one of which preceded and one of which followed peptide infusion. Administration of ACTH-(1 24) elevated cortisol levels in serum 1.6-fold and those in urine 2.2-fold, without affecting adrenal androgen concentrations. In the follicular phase (FP) of the menstrual cycle, infusion of ACTH-(1-24) did not alter serum levels of estradiol, FSH, or LH. However, immunoreactive estrone excretion in urine was decreased by 71% (P less than 0.05), and serum concentrations of sex hormone binding globulin (SHBG) were increased by 100% (P less than 0.01). In the luteal phase (LP) of the menstrual cycle, infusion of ACTH-(1-24) suppressed levels of serum estradiol by 54% (P less than 0.001), urinary immunoreactive estrone by 72% (P less than 0.05), serum progesterone by 53% (P less than 0.001), and urinary immunoreactive pregnanediol by 71% (P less than 0.01). Serum FSH concentrations were increased during treatment by 100% (P less than 0.001) in LP, but LH concentrations were not altered. Also, serum levels of SHBG returned to control values in the LP. The lengths of menstrual cycles and the lengths of FP or LP were not affected during or after treatment. These data provide evidence that subchronic infusion of ACTH-(1-24) in primates: 1) suppresses estradiol production by the ovarian follicle as well as estradiol and progesterone production by the corpus luteum, 2) compromises ovarian function without concomitant suppression of serum gonadotropin levels, and 3) induces a transitory elevation of SHBG levels in the circulation, which may compensate for reduced estrogen output. PMID- 1597157 TI - Serum concentrations of relaxin, chorionic gonadotropin, estradiol-17 beta, and progesterone during the reproductive cycle of the chimpanzee (Pan troglodytes). AB - Levels of serum relaxin were measured by a specific RIA and correlated with serum patterns of estradiol-17 beta, progesterone, LH, or cCG during a single menstrual cycle in each of 10 female chimpanzees, and throughout 24 pregnancies in 21 chimpanzees. Significant concentrations of relaxin, higher than those reported for the human being, were detected in serum of nonpregnant chimpanzees during the late luteal phase of the menstrual cycle. During pregnancy in the chimpanzee, serum relaxin concentrations, exceeding levels found during the luteal phase, were highest during the first third of gestation, and declined thereafter. Although the absolute concentrations were higher, the patterns of relaxin secretion throughout the reproductive cycle in chimpanzees was qualitatively very similar to that observed in other primates, including the human being. The chimpanzee should thus provide a useful model for examining the role of relaxin in human reproduction. PMID- 1597158 TI - Inhibition of hypothalamic neuropeptide Y gene expression by insulin. AB - Insulin acts in the brain to suppress feeding, whereas neuropeptide Y (NPY) has the opposite effect. Since fasting lowers plasma insulin levels and increases hypothalamic synthesis of NPY, we proposed that insulin may inhibit hypothalamic NPY gene expression. To test this hypothesis, we used RIA and in situ hybridization histochemistry to determine if centrally administered insulin could reduce levels of both NPY and its messenger RNA (mRNA) in discreet hypothalamic regions during fasting. Three groups of Long-Evans rats were entered into a 72-h study protocol. One group was fed ad libitum during this period, while the others were fasted. Fed rats received intracerebroventricular (icv) injections of saline vehicle at 12-h intervals, whereas fasted groups received icv vehicle alone or with insulin (4 mU/12 h). In vehicle-only treated rats, fasting significantly increased expression of preproNPY mRNA in the arcuate nucleus to 179 +/- 20% of fed controls. Administration of icv insulin during fasting abolished this increase (99 +/- 14% of fed controls; P less than 0.05 vs. fasted, vehicle treated rats). Central insulin administration during fasting also reduced immunoreactive NPY concentrations in samples punched from the paraventricular nucleus (PVN) (875 +/- 122 pg/punch) to levels below vehicle-only treated rats (1396 +/- 435 pg/punch; P less than 0.05), similar to free-feeding control values (814 +/- 170 pg/punch). By comparison, neither fasting nor central insulin administration altered NPY levels in four other hypothalamic regions (supraoptic, ventromedial, dorsomedial, and arcuate nuclei). Continuous icv insulin infusion at a lower dose (2 mU/day) produced a similar result during a shorter period (48 h) of food deprivation in Wistar rats. In this study, central insulin infusion also inhibited the fasting-related increase in arcuate preproNPY mRNA levels and did not affect plasma glucose or insulin levels. This suggests that insulin acts locally to inhibit hypothalamic NPY mRNA expression. We conclude that the increase of levels of NPY in the PVN and preproNPY mRNA in the arcuate nucleus during fasting are inhibited by icv insulin. Fasting, therefore, increases NPY biosynthesis along an arcuate nucleus-PVN pathway in the hypothalamus via a mechanism dependent on low insulin levels. PMID- 1597159 TI - Endothelin inhibits osteoclastic bone resorption by a direct effect on cell motility: implications for the vascular control of bone resorption. AB - The abundance of endothelin (ET)-producing endothelial cells in bone marrow and the proximity of these cells to bone-resorbing osteoclasts prompted us to evaluate the action of ET-1 on osteoclast function. Osteoclasts disaggregated from neonatal rat long bones were settled onto devitalized cortical bone substrate, and resorption was quantified by morphometry. The supernatant tartrate resistant acid phosphatase activity was determined by a spectrophotometric method using paranitrophenol phosphate as substrate. Cell motility was quantified by time lapse video- and computer-assisted image processing using an empirical procedure for morphometric analysis. Cytosolic free calcium levels ([Ca2+]i) were measured in single cells by an indo 1-based microspectrofluorimetric method. Using the area of bone resorbed per slice as response, we found that ET-1 caused a significant (P = 0.011) concentration-dependent inhibition of osteoclastic bone resorption (EC50 = 2.5 nM) without inhibiting acid phosphatase secretion. Exposure of isolated osteoclasts to ET-1 also led to a marked concentration dependent inhibition of osteoclast motility (EC50 = 7.9 nM; P = 0.013; t1/2 = 18 min) without significant effects on cell spread area. These effects of ET-1 were reversible after removing the peptide, and the cells remained viable during the experiments. In addition, ET-1 did not elevate [Ca2+]i at the concentrations tested. The results suggest that ET-1 specifically interacts with an osteoclast receptor to inhibit osteoclastic bone resorption and cell motility. As the concentration of ET-1 required for osteoclast inhibition was similar to that reported for smooth muscle contraction, it is possible that ET-1, produced locally from the bone marrow endothelial cell, might play a primary role in osteoclast regulation. PMID- 1597160 TI - Characterization of an antiidiotypic antibody mimicking the actions of estradiol and its interaction with estrogen receptors. AB - The ability of a monoclonal antiidiotypic antibody (clone 1D5) directed against the binding site of a monoclonal antiestradiol antibody to interact with the estrogen receptor (ER) was investigated. The following lines of evidence indicate that clone 1D5 has the capacity of mimicking the actions of estradiol, and recognizes ER: 1) in binding experiments, clone 1D5 inhibited the binding of [3H]estradiol to porcine cytosolic 32-kilodalton ER fragment in a dose-dependent manner; irrelevant antibody had no effect; 2) in sucrose gradient density analysis, clone 1D5 abolished the specific peak of the [3H] estradiol-ER complex in the 4S region; 3) in immunoprecipitation experiments, clone 1D5 interacted with unoccupied ER, but not with estradiol-occupied ER; 4) in direct immunofluorescence studies clone 1D5 stained the nuclei of cultured rat epithelial cells and recognized estrogen binding sites in nuclear cryostat sections prepared from human, rat, and mouse estrogen-responsive tissues; and 5) When clone 1D5 was injected to immature female rats, it caused 46% increase in uterine creatine kinase activity, suggesting that clone 1D5 may possess estrogenic like activity. Under the same experimental conditions, estradiol caused 58% increase in creatine kinase activity. Collectively, these results suggest that clone 1D5 interacts with the steroid binding site of ER. Therefore, clone 1D5 can serve as a tool in the study of function and structure relationship of ER and to detect changes of ER levels in target cells of various species. PMID- 1597161 TI - Angiotensin-II-binding sites on hepatocyte nuclei. AB - Angiotensin-II (Ang II) stimulates gene expression and cell growth in several cell types. Studies that have shown localization of Ang II to nuclei of myocytes and hepatic nuclear Ang II binding suggest that these actions may be mediated by nuclear receptors. We characterized Ang II binding to rat liver nuclei, which were free of plasma membrane based on enzyme analysis and electron microscopy. At 18 C, specific binding of 0.1-0.3 nM [125I]Ang II to nuclei and nuclear envelopes reached equilibrium by 2 h. Unlabeled Ang II inhibited [125I]Ang II binding to nuclei with an IC50 of 1.4 +/- 0.2 nM (+/- SE; n = 6). In half of the nuclear preparations, a lower affinity site (IC50, 50.4 +/- 23.6 nM), which accounted for 7-32% of specific Ang II binding, was detected by Scatchard analysis. Results similar to these were obtained with nuclear envelopes. Other Ang peptides competed for binding in the rank order: Ang III (IC50, 2.1 nM) greater than Ang I (IC50, 33) greater than [Des-Phe8]Ang II (IC50, 362) greater than [Des-Asp1-Des Arg2]Ang II (IC50, 736). Losartan (DuP 753), an AT1 receptor antagonist, inhibited binding (IC50, 10.9 +/- 0.9 nM), whereas the AT2 receptor antagonist PD123177 did not. The pH optimum for binding to nuclear envelopes was 7, with binding more sensitive to low (5 and 6) than high (8 and 9) pH. Nonhydrolyzable GTP analogs accelerated displacement of bound [125I]Ang II by 10(-5) M Ang II. Differences were noted in pH sensitivity, time course, binding affinity for Ang I, II, and III, and rate of dissociation between nuclei or nuclear envelopes and plasma membrane Ang II binding. These results suggest that nuclear envelopes have a G-protein-coupled Ang II-binding site, which belongs to the AT1 class of Ang II receptors, with properties different from the plasma membrane receptor. PMID- 1597162 TI - Progestin target cell distribution in forebrain and midbrain regions of the 8-day postnatal mouse brain. AB - The present study investigated the anatomical distribution of progestin target cells throughout the forebrain and midbrain regions of the 8-day postnatal female mouse. Female ICR mice were sc injected with 100 micrograms/100 g BW estradiol valerate on postnatal day 5 (birth = day 0). On postnatal day 8, treated mice were sc injected with 0.32 micrograms/100 g BW (Z)-17 beta-hydroxy-17 alpha-(2 [125I]iodovinyl)4-estren-3-one ([125I] progestin). For competition, additional estrogen-treated mice were each injected with 320 micrograms R5020 (17,21 dimethyl-19-nor-4,9-pregnadiene-3,20-dione; a potent synthetic progestin), 320 micrograms dihydrotestosterone, or 32, 160, or 320 micrograms corticosterone 1 h before [125I]progestin to show the specificity of [125I]progestin for the progestin receptor. Two hours after injection of [125I]progestin, the brains were removed, frozen, and processed for high resolution thaw-mount autoradiography. After 8-60 days of exposure, nuclear uptake and retention of [125I]progestin were detected in many brain regions, including the septum; bed nucleus of the stria terminalis; and preoptic area, periventricular nucleus, ventromedial nucleus, arcuate nucleus, and dorsomedial nucleus of the hypothalamus. In addition, labeling was seen in the cerebral cortex, caudate putamen, hippocampus, amygdala, and substantia nigra. Competition studies showed that excess R5020 prevented nuclear concentration of ligand, while dihydrotestosterone and corticosterone did not. The results indicate that the distribution of progestin target cells in extrahypothalamic regions of the developing brain is more extensive than that in the adult, while a similar topography was seen in the preoptic area and hypothalamus. The results further suggest that progestin action during brain development may influence the growth and development of target cells not only in the hypothalamus but also in regions of the brain previously not considered to be sites of hormone action. PMID- 1597163 TI - Regulation of hepatic angiotensinogen synthesis and secretion by steroid hormones. AB - The regulation of angiotensinogen gene expression by steroid hormones in the rat liver has been examined. In the intact animal, dexamethasone (7 mg/kg ip) and estradiol (7 mg/kg sc) caused an increase in plasma angiotensinogen, which became first apparent after 5 or 9 h, respectively, and resulted in plasma concentrations 4.6- and 1.9-fold higher than in controls at 24 h. These changes were preceded by comparable increases in hepatic angiotensinogen messenger RNA (mRNA). In contrast, dihydrotestosterone (10 mg/kg sc) failed to alter plasma angiotensinogen, although hepatic angiotensinogen mRNA and total RNA were slightly elevated. In isolated hepatocytes exposed to either dexamethasone or estradiol (10 microM each) angiotensinogen mRNA started to increase within less than 1 or 3 h, respectively, followed, with a further time lag of about 2 h, by an increase in secretion rate of angiotensinogen. Dihydrotestosterone (10 and 100 microM) induced a rapid increase in total hepatocyte RNA (1.3-fold) and angiotensinogen mRNA (2-fold) with a peak at 2 h. Surprisingly, angiotensinogen secretion remained either unaltered (10 microM dihydrotestosterone) or even decreased (100 microM dihydrotestosterone). In a hepatoma cell line (FT02B) and a subclone (Fe 33) stably transfected with the human estrogen receptor, dexamethasone and estradiol induced an increase in angiotensinogen mRNA and secretion with the same characteristics as in hepatocytes. In conclusion, in this study a direct effect of estradiol on angiotensinogen mRNA and secretion in hepatocytes could be established, which differs from that of dexamethasone by a delayed onset of action. The observation, both in vivo and in vitro, that dihydrotestosterone induced an increase in total RNA and angiotensinogen mRNA, which is not accompanied by an increased angiotensinogen secretion, cannot be explained at present. This study also demonstrates the usefulness of a hepatoma cell line stably transfected with the estrogen receptor gene for the investigation of estrogen-dependent effects in vitro. PMID- 1597164 TI - The biological activity of 7 alpha-methyl-19-nortestosterone is not amplified in male reproductive tract as is that of testosterone. AB - Based on the premise that testosterone, but not 7 alpha-methyl-androgens, is reduced at the 5 alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7 alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7 alpha-methylated androgens were similar to that of MENT. The importance of 5 alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5 alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5 alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5 alpha-androst-1-ene-17 beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7 alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7 alpha-methylated androgens may offer some health benefits to men who require androgen treatment. PMID- 1597165 TI - The effects of extracellular calcium and epinephrine on cytosolic-free calcium in single rat adipocytes. AB - Changes in cytosolic calcium concentration ([Ca2+]i) in response to extracellular calcium and epinephrine were monitored in individual rat adipocytes by both photon counting and digital imaging techniques utilizing the intracellular fluorescent calcium probes Fura-2 and Indo-1. Adipocytes containing Fura-2 were attached to coverslips and shown to be as hormonally responsive to insulin as adipocytes in suspension [3.5 +/- 0.8 (n = 5) vs. 4.2 +/- 0.6 (n = 8)-fold increase in glucose oxidation over basal in response to 0.7 nM insulin]. Basal [Ca2+]i in single rat adipocytes was found to be 128 +/- 6 nM (n = 100). The addition of either extracellular calcium or epinephrine elicited transient, concentration-dependent increases in [Ca2+]i. Although the characteristics of calcium- and epinephrine-induced calcium transients are generally similar, the peak [Ca2+]i increase over basal is higher in response to calcium vs. epinephrine [37 and 64% (1 and 27 microM epinephrine), vs. 132 and 236% (2 and 4 mM calcium)]. All the cells tested responded to calcium but only 67% responded to epinephrine. Both alpha- and beta-adrenergic agonists were able to increase [Ca2+]i. The epinephrine-induced [Ca2+]i transients appear to be dependent upon extra-cellular calcium. Neither cholera nor pertussis toxin treatments altered basal [Ca2+]i. However, after treatment of adipocytes with either pertussis or cholera toxin, epinephrine stimulated oscillations in [Ca2+]i. Digital imaging revealed that adipocytes demonstrate a high degree of intracellular spatial heterogeneity and intercellular variability in the magnitude of response to both calcium and epinephrine. These studies demonstrate the feasibility of using single rat adipocytes to monitor intracellular free calcium, using both photon counting and digital imaging. PMID- 1597166 TI - Neonatal estrogen exposure induces lobe-specific alterations in adult rat prostate androgen receptor expression. AB - Brief administration of estrogen to newborn rats results in permanent suppression of prostate growth and reduced prostatic responsiveness to testosterone in adulthood. To determine whether this imprinting may be a result of alterations in androgen receptor (AR) expression, the separate adult prostate lobes of neonatally estrogenized rats were examined for AR concentration and distribution. Sprague-Dawley rat pups were given 25 micrograms estradiol benzoate or oil alone on days 1, 3, and 5 and were killed on day 90. Half of the animals received 2-cm testosterone implants 10 days before death to assess the activational response to androgen. In a separate series, neonatally estrogenized rats were given prepubertal dihydrotestosterone pellets for 3 weeks as well as testosterone implants in adulthood to determine if the observed effects of neonatal estrogen on the adult prostate were an indirect result of androgen deprivation during developmentally critical periods. The ventral, dorsal, and lateral prostate lobes were processed for nuclear AR quantitation by [3H]dihydrotestosterone exchange binding assay and for indirect immunocytochemical localization of AR. Weights and DNA contents of the three prostate lobes were significantly reduced in neonatally estrogenized rats, and this decrease was only partially reversed by prepubertal and/or adult androgen replacement. Histologically, the hypoplastic ventral and dorsal lobes exhibited a relative increase in interacinar stromal tissue, disorganized acini with epithelial hyperplasia, luminal sloughing, and an apparent lack of differentiation. The hypoplastic lateral lobe also showed a relative increase in the stromal fraction; however, the acinar epithelium appeared differentiated, with normal basal/apical orientation and luminal secretions. The AR concentration was significantly reduced in the ventral and dorsal prostates of estrogenized rats, but was unaltered in the lateral lobe. Immunocytochemistry revealed a marked reduction or absence of epithelial AR in ventral and dorsal lobes from estrogenized rats, whereas the lateral lobe epithelial cells expressed AR similarly to controls. The incidence of AR-positive fibroblastic stromal cells increased in lateral prostates from 5% in controls to approximately 25% in estrogenized rats. Neonatally estrogenized rats given testosterone for 10 days in adulthood showed increased levels of AR in the ventral and dorsal lobes compared to nonstimulated rats; however, these levels remained well below control values. Lateral lobe epithelial histology and AR expression appeared relatively unchanged in estrogenized rats given testosterone during adulthood, whereas an increased proportion of stromal cells (approximately 35%) were AR positive. In summary, neonatal estrogen administration permanently altered prostatic growth and produced lobe-specific changes in AR expression in the adult gland.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597167 TI - Epidemiologic analysis of an environmental disaster: the Schweizerhalle experience. PMID- 1597168 TI - Asbestos-containing materials in New York City buildings. AB - The New York City Department of Environmental Protection (DEP) carried out a survey to assess the public's risk of exposure in buildings to in-place asbestos containing materials (ACM). Data regarding the presence of in-place asbestos and the potential for exposure to asbestos were collected in 886 buildings from 16 different building categories in New York City. Overall 68% of the buildings in New York City contain ACM. The estimated total amount of ACM in the city is 323 million ft2 most of which is thermal system insulation. Overall, 16% of all ACM had greater than 10% of its surface damaged and another 68% of ACM had some, but less than 10% of its surface damaged. About half of all ACM is in mechanical spaces within buildings. On the basis of results of the survey, buildings in New York City were prioritized for management and an in-place management bill was introduced into the New York City Council. PMID- 1597169 TI - Macrophage reaction in rabbit lung following inhalation of iron chloride. AB - Groups of eight rabbits were inhalation-exposed to iron, 1.4 +/- 0.7 mg/m3 (low Fe), or 3.1 +/- 1.8 mg/m3 (high Fe) as FeCl3 or to filtered air (controls) for 2 months, 5 days/week and 6 hours/day. The alveolar macrophages were increased in number in both exposed groups. Noduli of granular macrophages were found in lungs of all the rabbits in the high-Fe group, in one from the low-Fe group, and in one control rabbit. Especially in the high-Fe group there were prominent changes in the macrophages such as enlarged lysosomes containing fibrous-looking structures, iron-rich inclusions, and densely packed, 5-nm electron-dense granules. The number of cells filled with surfactant-like inclusions as well as a smooth surface was increased in the high-Fe group and the macrophages had enhanced phagocytic capacity. There was an increase in the phospholipid concentration and in the volume density of type II cells in the high-Fe group but the level of phosphatidylcholines was not significantly changed. The fact that Fe3+ affected mainly the alveolar macrophages might be due to the relatively high concentration of iron in these cells caused by the precipitation of iron in their lysosomes. PMID- 1597170 TI - Rabbit lung after combined exposure to soluble cobalt and trivalent chromium. AB - Eight rabbits were exposed to 0.7 +/- 0.4 mg/m3 Co2+ as CoCl2 and 1.2 +/- 0.7 mg/m3 Cr3+ as Cr(NO3)3 (group Co + Cr), eight to 0.6 +/- 0.5 mg/m3 Co2+ (group Co), and eight to filtered air (control group), for 4 months, 5 days/week, and 6 hr/day. All rabbits in group Co + Cr and group Co showed nodular aggregation of alveolar epithelial type II cells. Volume density of the type II cells was significantly higher in group Co + Cr than in group Co and the control group. There was intraalveolar macrophage accumulation in seven rabbits in group Co + Cr, one in group Co, and one in the control group. In lavage fluid the numbers of macrophages and the percentage of these cells with smooth surface and intracellular surfactant-like inclusions were more increased in group Co + Cr than in group Co as were oxidative metabolic and phagocytic activities of the macrophages. Total phospholipids, phosphatidylcholines, and especially 1,2 dipalmitoylphosphatidylcholine was markedly increased in group Co + Cr whereas only 1,2-dipalmitoylphosphatidylcholine was slightly increased in group Co. One mechanism behind the high amount of surfactant phospholipids in group Co + Cr seems to be an enhanced production of surfactant by the type II cells. Another mechanism is probably that Cr3+ reduces the capacity of alveolar macrophages to catabolize surfactant. The results imply that it is important to investigate effects of combinations of cobalt and chromium in the occupational environment. PMID- 1597171 TI - Net shoulder joint moment and muscular activity during light weight-handling at different displacements and frequencies. AB - The purpose of this study was to calculate net shoulder (gleno-humeral) joint moments from inverse dynamics and to measure muscular activity from six shoulder muscles (supraspinatus, infraspinatus, middle deltoid, anterior deltoid, trapezius, and pectoralis major) during light weight-handling at two different displacements (horizontal and vertical) and frequencies (40 and 60 cycles/min), to simulate an occupational cervicobrachial working task (light weight displacement). Ten normal adult male subjects were asked to move a known weight, representing 15% of the maximal lifted weight, in both horizontal and vertical conditions at frequencies of 40 cycles/min and 60 cycles/min. Raw EMG signals from six shoulder muscles were recorded and synchronized with the cinematographic data during three trials of 6 s each. The raw EMG signals of each muscle were full wave rectified and filtered at 3 Hz. The linear envelope (LE EMG) signals were normalized by time (% cycle) and by amplitude (% MVC), and for the analysis of variance, the normalized LE EMG signals were integrated (IN LE EMG). The average shoulder angular velocities, joint moments, and moment powers were computed from cinematographical data. No significant differences were observed between both tasks for the supraspinatus, infraspinatus, and pectoralis major IN LE EMG data as well as for integrated normalized shoulder joint moment for the whole cycle of movement. IN LE EMG data from middle deltoid, anterior deltoid, and trapezius muscles were significantly higher (p less than 0.05) when performing the vertical displacement task for the whole cycle of movement. This muscular activity difference between vertical and horizontal tasks indicated that the vertical displacement conditions induced higher muscular loads on the shoulder than the horizontal weight displacement conditions, although the vertical displacements were approximately 15% longer than the horizontal displacements. The non-significant difference of IN LE EMG between frequencies obtained for all muscles indicated that neither frequencies induced more muscular activity. PMID- 1597172 TI - Decrease in back strength in asymmetric trunk postures. AB - The extension force against resistance was recorded in 23 postures for 12 subjects to find explanations for the decrease in back strength in asymmetric postures. A reduction in muscle force in asymmetric postures was found up to 40%, but was strongly dependent on the plane in which asymmetry occurred, and on the posture to which it referred. A quantitative relationship between the forces exerted in different asymmetric postures is discussed, as a basis for formulating universal ergonomic guidelines for optimal working postures. The reduction in force in different asymmetric postures can be explained by length of the muscle, the activation of the muscle, and the moment angle of the muscle. PMID- 1597173 TI - Prediction of the metabolic cost of walking with and without loads. AB - Measurement of the metabolic cost of walking inconveniences subjects, and requires skilled technical support and expensive equipment. These factors have stimulated interest in predictive equations. The present study assessed existing equations. Under each of 17 combinations of gradient (0-6%) and carried load (4.1 37.4 kg), 7-12 men undertook treadmill walking at 1.67 m/s. Measured oxygen consumption and respiratory exchange ratio were used to calculate metabolic rate (MRobserved). Metabolic rate was also predicted from the equation of Pandolf et al. (1977) (MRpandolf) and, where appropriate, from another five equations relating to walking without loads. MRobserved and MRpandolf did not differ significantly (p greater than 0.05) under any combination of gradient and load. The overall mean MRobserved and MRpandolf of 609 W and 602 W, respectively, also did not differ significantly (p greater than 0.05). These variables were highly correlated (r = 0.94) with a standard deviation about the prediction error of 47 W. For level walking without loads, the mean predictions from the equations of Pandolf et al. (1977) and Cotes and Meade (1960) did not differ significantly (p greater than 0.05) from the mean MRobserved of 428 Watts, but four other equations overestimated by 17-74 W. In conclusion, the Pandolf et al. (1977) equation has given good results across the range of combinations of load and gradient tested, and the errors are considered acceptable for most practical purposes. PMID- 1597174 TI - Influence of body segment dynamics on loads at the lumbar spine during lifting. AB - Flexion-extension moments acting at the L5/S1 level and hip joints were calculated using three different techniques; a pure static analysis, a static analysis including the inertial force of the load, and a dynamic analysis. Ten subjects participated in the study and were asked to lift a box weighing either 50 N or 150 N, using a freestyle technique. The lifts were performed at normal and fast speed. The intra-subject lifting techniques were consistent when lifting the same loads. The moments predicted by the dynamic analysis and the static analysis were the same when holding weights in static postures. When performing the lifts, differences in the peak moments occurred between static and dynamic analyses. These differences were influenced by external load and by lifting speed. Taking the effect of the inertia of load into account in the static analysis resulted in an increase in the moment magnitude, but the predicted moment was still much less than in the dynamic analysis which yielded the largest moment magnitudes. The difference between dynamic and static analysis was greatest when lifting 50 N at fast speed; an 87% increase in L5/S1 moment and a 95% increase in hip moment was observed when replacing the pure static with a dynamic analysis. PMID- 1597175 TI - Physiological and perceptual responses to load-carrying in female subjects using internal and external frame backpacks. AB - Eleven female subjects (ages 18-33 years) walked on a motor-driven treadmill at 86 m/min for 1 h carrying 33% of their body weight in a backpack. The grade of the treadmill alternated every 15 min between 0 and 3%. Each subject carried an internal frame backpack for one trial and an external frame backpack for another trial on a separate day. The variables measured during the two load-carrying experiments included oxygen consumption (VO2), heart rate (HR), respiratory exchange ratio (R), minute ventilation VE, and the ratings of perceived exertion for the chest (RPE-chest), shoulders (RPE-shoulders), and legs (RPE-legs). When oxygen uptake measured during load-carrying was expressed as a percentage of VO2max, the average values were 40.1% (63.5% HRmax) at 0% grade and 49.0% (69.6% HRmax) at 3% grade for both backpacks. No significant differences were found between the two packs for any of the metabolic, cardiorespiratory, or perceptual variables measured. Changes in treadmill grade had a significant effect on VO2, HR, and VE, regardless of the type of pack carried. Minute ventilation was the only physiological response to load-carrying that increased significantly as exercise duration increased. The values for RPE-chest, RPE-shoulders, and RPE legs were significantly increased by both exercise time and treadmill slope, regardless of the type of pack frame carried. Thus despite relatively constant metabolic responses over time, increased perception of effort could compromise completion of the load-carrying task. It was concluded that differences in backpack frame design were not great enough to produce significant differences in the energy cost or perception of carrying a moderately heavy load on the back. PMID- 1597176 TI - Carbon catabolite repression in yeast. PMID- 1597177 TI - cDNA cloning of rice lipoxygenase L-2 and characterization using an active enzyme expressed from the cDNA in Escherichia coli. AB - A full-length cDNA of rice lipoxygenase L-2 was cloned from 3-day-old seedlings. The identity of the clone was determined by amino acid sequencing of selected peptides of the purified enzyme and immunological characterization of an active enzyme that was produced from the cDNA in Escherichia coli by cultivation at 15 degrees C. The nucleotide sequence showed a strong bias toward G and C in the selection of nucleotides, especially at the third position of the codons (93% G/C). The complete amino acid sequence of the enzyme was deduced from the nucleotide sequence. The molecular mass of the enzyme was calculated to be 96,657 Da based on 865 amino acids. The amino acid sequence shares similarity with those of dicot lipoxygenases throughout the enzyme at a level of 50%. A hydropathy profile calculated from the amino acid sequence resembled those of dicot lipoxygenases, suggesting conservation of the secondary structure of these enzymes. The active enzyme, expressed in Escherichia coli, was characterized for pH dependence of the enzyme activity, intramolecular specificity, heat stability and Km. The enzyme had the same properties as the L-2 enzyme that was isolated from seedlings, but differed from the lipoxygenase L-3 isolated from mature plants. PMID- 1597178 TI - Properties of yeast debranching enzyme and its specificity toward branched cyclodextrins. AB - Debranching enzyme was purified from Saccharomyces cerevisiae by DEAE-cellulose, omega-aminobutyl agarose and hydroxyapatite column chromatography. The activity of the eluent was monitored by the iodine-staining method which detects both the direct and indirect debranching enzymes. The elution profiles at every step showed a single peak with no shoulder. The crude and the purified enzyme preparations gave a single activity band with the same mobility on PAGE. The crude product produced 80% glucose compared to reducing sugar from glycogen phosphorylase-limited dextrin while the partially purified and purified preparations produced 100% glucose. The activity of the purified enzyme was characterized and compared with that of the rabbit muscle enzyme by using various branched cyclodextrins as substrates. Both enzymes hydrolyzed 6-O-alpha-D glucosyl cyclodextrins to glucose and cyclodextrins, but did not act on 6-O-alpha maltosyl cyclomaltoheptaose. The yeast enzyme gave rise to glucose as a sole reducing sugar from 6-O-alpha-maltotriosyl cyclomaltoheptaose and 6-O-alpha maltotetraosyl cyclomaltoheptaose, indicating that maltosyl and maltotriosyl transfers, respectively, had occurred, prior to the action of amylo-1,6 glucosidase. 6-O-alpha-D-Glucosyl cyclomaltoheptaose and 6-O-alpha-D-glucosyl cyclomalto-octaose, respectively, were better substrates than glycogen phosphorylase-limited dextrin for the yeast and muscle enzymes. The yeast enzyme released glucose at a similar rate from 6-O-alpha-maltotriosyl cyclomaltoheptaose as from 6-O-alpha-maltotetraosyl cyclomaltoheptaose, but considerably lower rates than that from limit dextrin. The yeast debranching enzyme appears to be exclusively oligo-1,4----1,4-glucantransferase-amylo-1,6-glucosidase and does not have isoamylase. PMID- 1597179 TI - Purification and characterization of a thermostable carboxypeptidase from the extreme thermophilic archaebacterium Sulfolobus solfataricus. AB - A carboxypeptidase was purified to electrophoretic homogeneity from the thermoacidophilic archaebacterium Sulfolobus solfataricus. Molecular masses assessed by SDS/PAGE and gel filtration were 42 kDa and 170 kDa, respectively, which points to a tetrameric structure for the molecule. An isoelectric point of 5.9 was also determined. The enzyme was proven to be a metalloprotease, as shown by the inhibitory effects exerted by EDTA and o-phenanthroline; furthermore, dialysis against EDTA led to a complete loss of activity, which could be restored by addition of Zn2+ in the micromolar range, and, to a lesser extent, by Co2+. The enzyme was endowed with a broad substrate specificity, as shown by its ability to release basic, acidic and aromatic amino acids from the respective benzoylglycylated and benzyloxycarbonylated amino acids. An esterase activity of the carboxypeptidase was also demonstrated on different esterified amino acids and dipeptides blocked at the N-terminus. The enzyme displayed broad pH optima ranging over 5.5-7.0, or 5.5-9.0, when using an acidic or a basic benzyloxycarbonylated amino acid, respectively. With regard to thermostability, it was proven to be completely stable on incubation for 15 min at 85 degrees C. Furthermore, thanks to its relatively low activation energy, i.e. 31.0 kJ/mol, it was still significantly active at room temperature. At 40 degrees C, the enzyme could withstand 0.1% SDS and different organic solvents: particularly ethanol up to 99%. Amino acid and N-terminal sequence analyses did not evidence any similarity to carboxypeptidases A nor thermolysin. A weak similarity was only found with bovine carboxypeptidase B. PMID- 1597180 TI - Biochemical and photochemical properties of the photophobic receptors from Halobacterium halobium and Natronobacterium pharaonis. AB - The phototaxis of Halobacterium halobium is initiated by two photoreceptors, the sensory rhodopsins sR-I and sR-II. An sR-II-like pigment has also been described in Natronobacterium pharaonis. In this work it was shown that N. pharaonis cells are repelled by light with a wavelength of 500 nm. A further comparison of membrane preparations from H. halobium (mutant D1) containing only sR-II and from N. pharaonis [strain SP1(28)] with a chromophoric protein (psR-II) resembling sR II revealed substantial similarities. The biochemical and photochemical properties of the pigments are quite similar, with psR-II being more stable to external conditions such as pH and ionic strength of the buffer. Both pigments are bleached by low concentrations of hydroxylamine and can be reconstituted by the addition of all-trans-retinal. The absorption spectrum of psR-II is quite similar to sR-II including the shoulder on the short-wavelength side. After light excitation sR-II and psR-II undergo photocycles with at least three intermediates. The earliest intermediate has an absorption maximum above 520 nm and decays to a species which has a characteristic absorption (approximately 380 nm) of a deprotonated Schiff base. The final step is the regeneration of the original ground state via a red-shifted intermediate absorbing around 540 nm. From this cumulative evidence it can be concluded that, not only sR-II, but also the pigment from N. pharaonis is a photophobic photoreceptor. PMID- 1597181 TI - YmL9, a nucleus-encoded mitochondrial ribosomal protein of yeast, is homologous to L3 ribosomal proteins from all natural kingdoms and photosynthetic organelles. AB - The nuclear gene for mitochondrial ribosomal protein YmL9 (MRP-L9) of yeast has been cloned and sequenced. The deduced amino acid sequence characterizes YmL9 as a basic (net charge + 30) protein of 27.5 kDa with a putative signal peptide for mitochondrial import of 19 amino acid residues. The intact MRP-L9 gene is essential for mitochondrial function and is located on chromosome XV or VII. YmL9 shows significant sequence similarities to Escherichia coli ribosomal protein L3 and related proteins from various organisms of all three natural kingdoms as well as photosynthetic organelles (cyanelles). The observed structural conservation is located mostly in the C-terminal half and is independent of the intracellular location of the corresponding genes [Graack, H.-R., Grohmann, L. & Kitakawa, M. (1990) Biol. Chem. Hoppe Seyler 371, 787-788]. YmL9 shows the highest degree of sequence similarity to its eubacterial and cyanelle homologues and is less related to the archaebacterial or eukaryotic cytoplasmic ribosomal proteins. Due to their high sequence similarity to the YmL9 protein two mammalian cytoplasmic ribosomal proteins [MRL3 human and rat; Ou, J.-H., Yen, T. S. B., Wang, Y.-F., Kam, W. K. & Rutter, W. J. (1987) Nucleic Acids Res. 15, 8919-8934] are postulated to be true nucleus-encoded mitochondrial ribosomal proteins. PMID- 1597182 TI - Conformational and functional properties of peptides covering the intersubunit region of influenza virus hemagglutinin. AB - The functionally active part of influenza virus hemagglutinin was investigated through the synthesis of a series of peptides representing different parts of the intersubunit region. Secondary structure prediction, circular dichroism and Fourier transform infrared spectroscopic studies were undertaken to investigate the secondary structure of these peptides. The peptide fragments were found to adopt multiple conformations, depending on their concentration in solution, the presence of the non-ionic detergent octyl-beta-D-glucoside and the polarity of the solvent. The results of biological studies with these peptide fragments are discussed in relation to their conformation, as inferred from the spectroscopic analysis. PMID- 1597183 TI - Reconstitution of pyruvate dehydrogenase multienzyme complexes based on chimeric core structures from Azotobacter vinelandii and Escherichia coli. AB - Two unique restriction sites were introduced by site-directed mutagenesis at identical positions in the DNA encoding the dihydrolipoyltransacetylase (E2p) components of the pyruvate dehydrogenase complex from Azotobacter vinelandii and from Escherichia coli. In this manner each DNA chain could be cut into three parts, coding for the lipoyl domain, which consists of three lipoyl subdomains, the binding domain and the core-forming catalytic domain, respectively. Chimeric E2p components were constructed by exchanging the three domains between E2p from A. vinelandii and E. coli on gene level. The six chimeric E2p proteins were expressed and purified from E. coli TG2. All chimeras were catalytically active, 24-subunit E2p proteins. Interactions of the peripheral components E1p and E3 with the wild-type enzymes from A. vinelandii and E. coli and with the chimeric proteins were studied by gel-filtration experiments, analytical ultracentrifugation and reconstitution of the overall activity of the complex. A. vinelandii E3 interacts only with those chimeras that contain the A. vinelandii binding domain, whereas E. coli E3 interacts with all chimeras. Exchange of the lipoyl or catalytic domain did not influence the binding properties of E3. Recognition of E1p depends on the origin of both the binding domain and the catalytic domain. E. coli E1p interacts strongly with those chimeras in which both the binding domain and the catalytic domain were derived from E. coli E2p and weakly with chimeras that contained either the binding domain or the catalytic domain from E. coli E2p. No binding of E. coli E1p was observed when both domains were of A. vinelandii origin. A. vinelandii E1p recognizes E2p from A. vinelandii and E. coli, but strong interaction required that the binding and catalytic domain were of the same origin. Exchange of lipoyl domains had no effect on the binding properties of the E1p component. These observations confirm previous conclusions, based on site-directed mutagenesis of A. vinelandii E2p [Schulze, E., Westphal, A. H., Boumans, H., and de Kok, A. (1991) Eur. J. Biochem. 202, 841-848], that the binding site for E1p consists of amino acid residues derived from both the binding and the catalytic domain and extend these conclusions to E. coli E2p. Dissociation of the 24 subunit E2p core was only detected when the chimeric E2p proteins contained the catalytic domain from A. vinelandii E2p. Dissociation depends on the binding of peripheral components to the E1p-binding sites, pointing to differences in the inter-trimer contacts between the E2p proteins from both species.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597184 TI - Crystal structure of NAD-dependent formate dehydrogenase. AB - The ternary complex of NAD-dependent formate dehydrogenase (FDH) from the methylotrophic bacterium Pseudomonas sp. 101 (enzyme-NAD-azide) has been crystallised in the space group P2(1)2(1)2(1) with cell dimensions a = 11.60 nm, b = 11.33 nm, c = 6.34 nm. There is 1 dimeric molecule/asymmetric unit. An electron density map was calculated using phases from multiple isomorphous replacement at 0.30 nm resolution. Four heavy atom derivatives were used. The map was improved by solvent flattening and molecular averaging. The atomic model, including 2 x 393 amino acid residues, was refined by the CORELS and PROLSQ packages using data between 1.0 nm and 0.30 nm excluding structure factors less than 1 sigma. The current R factor is 27.1% and the root mean square deviation from ideal bond lengths is 4.2 pm. The FDH subunit is folded into a globular two domain (coenzyme and catalytic) structure and the active centre and NAD binding site are situated at the domain interface. The beta sheet in the FDH coenzyme binding domain contains an additional beta strand compared to other dehydrogenases. The difference in quaternary structure between FDH and the other dehydrogenases means that FDH constitutes a new subfamily of NAD-dependent dehydrogenases: namely the P-oriented dimer. The FDH nucleotide binding region of the structure is aligned with the three dimensional structures of four other dehydrogenases and the conserved residues are discussed. The amino acid residues which contribute to the active centre and which make contact with NAD have been identified. PMID- 1597185 TI - A novel photoactivatable cross-linker for the functionally-directed region specific fluorescent labeling of proteins. AB - A cleavable cross-linking reagent, sulfosuccinimidyl-2(7-azido-4-methylcoumarin-3 acetamido)-ethyl-1,3'- dithiopropionate (SAED), was synthesized for the selective transfer of a coumarin fluorophore from a 'donor' protein to a position near the binding site of an interacting 'target' protein. SAED contains a terminal N sulfosuccinimidyl ester for conjugation to the donor, a terminal photoactivatable azido-coumarin species for cross-linking with the interacting target, and a central disulfide spacer for the release of the labeled target after cleavage. To evaluate the effectiveness of this labeling reagent, soybean trypsin inhibitor (STI) was derivatized (approximately 0.5 mol/mol) with SAED and then photolyzed in the presence of trypsin. A single fluorescent cross-linked species (6-7 mol% of total STI) was observed by SDS/PAGE and, after reductive cleavage, was shown to be a 1:1 STI-trypsin complex. This complex was not detected without photolysis or with an inactivated cross-linker. Importantly, complex formation was inhibited by an excess of unmodified STI and prevented by substitution of a non-interacting protein for trypsin. Cleavage of the cross-linked complex revealed that the trypsin, but not the STI, was fluorescent; the uncomplexed trypsin fraction remained unlabeled. These results demonstrated the specificity of the labeling of trypsin by fluorescent-transfer cross-linking with SAED. An efficiency of about 15% for this cross-linking mediated labeling of trypsin was calculated. The short cross-linking span of SAED (less than or equal to 1.8 nm) strictly limited the labeling to the vicinity of the contact region of trypsin with STI. Thus, this novel cross-linker permits the region-specific targeting of a fluorophore near a functionally important binding site. PMID- 1597186 TI - Frontier orbital study on the 4-hydroxybenzoate-3-hydroxylase-dependent activity with benzoate derivatives. AB - Based on molecular orbital computer calculations the present paper provides a new hypothesis for catalytic characteristics of 4-hydroxybenzoate-3-hydroxylase (EC 1.14.13.2). A clear correlation between in kcat for the conversion of a series of 4-hydroxylated substrates and their E(HOMO) leads to the hypothesis that Frontier orbital HOMO characteristics [E(HOMO) and HOMO density on C3] of the substrates are the predominant factor in regulating the fate of a benzoate derivative at the active site of the enzyme. The HOMO characteristics can be used to explain whether a compound will be converted by the enzyme or merely acts as an effector. Furthermore, the hypothesis provides quantitative theoretical support for a catalytic mechanism in which the substrate reacts in its dianionic form and for a mechanism in which the electrophilic attack of the C(4a)-peroxyflavin, or of the hydroxyl radical derived from it, on the benzoate dianion is the rate limiting step in catalysis at pH 8, 25 degrees C. Finally, it is demonstrated that the hypothesis can be used as a basis for the formulation of working hypotheses in future research, investigating the conversion and regioselective orientation of the various possible substrates in the active site of the wild-type 4 hydroxybenzoate-3-hydroxylase, its mutants as well as of various other flavin dependent aromatic hydroxylases, such as for example 3-hydroxybenzoate-4 hydroxylase (EC 1.14.13.23), 3-hydroxybenzoate-6-hydroxylase (EC 1.14.13.24) and phenol hydroxylase (EC 1.14.13.7). PMID- 1597187 TI - Mammalian thymidine kinase 2. Direct photoaffinity labeling with [32P]dTTP of the enzyme from spleen, liver, heart and brain. AB - Thymidine kinase 2 (TK2), also called mitochondrial thymidine kinase, is a pyrimidine deoxyribonucleoside kinase expressed in all cells and tissues. It was recently purified to apparent homogeneity from human leukemic spleen and the active enzyme was shown to be a monomer of a 29-kDa polypeptide. The enzyme is feedback-inhibited by both end products, dCTP and dTTP. Here we show that TK2 purified from several different sources, including purified beef heart mitochondria, could be directly photoaffinity labeled with radioactive dTTP (approximately 18% of all TK2 molecules were cross-linked to dTTP after 20 min of ultraviolet irradiation) or to a lower extent with dCTP. Photo-incorporation was inhibited by the presence of the other effector but also the phosphate donor ATP blocked photolabeling, with dTTP. Addition of nucleoside substrates gave only a marginal inhibition of photo-incorporation. There were no detectable difference in the molecular size of photolabeled TK2 isolated from human spleen, brain or placenta, monkey liver, beef heart and beef heart mitochondria. Nor was there any significant differences in the enzyme kinetic properties of these enzymes. Cleavage of labeled TK2 with cyanogen bromide showed that dTTP was incorporated into a single 3-kDa peptide. TK2 was the only pyrimidine deoxynucleoside kinase expressed in liver, heart and brain. A detailed characterization of the subunit structure and substrate specificity of this enzyme is of importance for the design of new antiviral and cytostatic therapies based on nucleoside analogs. PMID- 1597188 TI - Purification and properties of prostaglandin 9-ketoreductase from pig and human kidney. Identity with human carbonyl reductase. AB - Prostaglandin 9-ketoreductase (PG-9-KR) was purified from pig kidney to homogeneity, as judged by SDS/PAGE using an improved procedure. The enzyme is pro S stereoselective with regard to hydrogen transfer from NADPH with prostaglandin E2 as substrate and reduces its 9-keto group with approximately 90% stereoselectivity to form prostaglandin F2 alpha. Approximately 8% of the prostaglandin F formed has the beta-configuration. In addition to catalyzing the interconversion of prostaglandin E2 to F2 alpha, PG-9-KR also oxidizes prostaglandin E2, F2 alpha and D2 to their corresponding, biologically inactive, 15-keto metabolites. Incubation of PG-9-KR with prostaglandin F2 alpha and NAD+ leads to the preferential formation of 15-keto prostaglandin F2 alpha rather than prostaglandin E2. This suggests that the prostaglandin E2/prostaglandin F2 alpha ratio is not determined by the NADP+/NADPH redox couple. The enzyme also reduces various other carbonyl compounds (e.g. 9,10-phenanthrenequinone) with high efficiency. The catalytic properties measured for PG-9-KR suggest that its in vivo function is unlikely to be to catalyze formation of prostaglandin F2 alpha. The monomeric enzyme has a molecular mass of 32 kDa and exists as four isoforms, as judged by isoelectric focusing. PG-9-KR contains 1.9 mol Zn2+/mol enzyme and no other cofactors. Human kidney PG-9-KR was also purified to homogeneity. The human enzyme has a molecular mass of 34 kDa and also exists as four isoforms. Polyclonal antibodies raised against pig kidney PG-9-KR cross-react with human kidney PG-9-KR and also with human brain carbonyl reductase, as demonstrated by Western blot analysis. Sequence data of tryptic peptides from pig kidney PG-9-KR show greater than 90% identity with human placenta carbonyl reductase. From comparison of several properties (catalytical, structural and immunological properties), it is concluded that PG-9-KR and carbonyl reductase are identical enzymes. PMID- 1597189 TI - Cloning and nucleotide sequence of the psrA gene of Wolinella succinogenes polysulphide reductase. AB - The polysulphide reductase (formerly sulphur reductase) of Wolinella succinogenes is a component of the phosphorylative electron transport system with polysulphide as the terminal acceptor. Using an antiserum raised against the major subunit (PsrA, 85 kDa) of the enzyme, the corresponding gene (psrA) was cloned from a lambda-gene bank. The N-terminal amino acid sequence of PsrA mapped within the psrA gene product, which also contained an apparent signal peptide. Downstream of the psrA gene two more open reading frames (psrB and psrC) were found. The three genes may form a transcriptional unit with the transcription start site in front of psrA. The three genes were present only once on the genome. PsrA is a hydrophilic protein homologous to the largest subunits of six prokaryotic molybdoenzymes. PsrB is predicted to be hydrophilic, to contain ferredoxin-like cysteine clusters and to be homologous to the smaller hydrophilic subunits of four molybdoenzymes. PsrC is predicted to be a hydrophobic protein that could possibly serve as the membrane anchor of the enzyme. PMID- 1597190 TI - NAD-linked, factor-dependent formaldehyde dehydrogenase or trimeric, zinc containing, long-chain alcohol dehydrogenase from Amycolatopsis methanolica. AB - NAD-linked, factor-dependent formaldehyde dehydrogenase (FD-FA1DH) of the Gram positive methylotrophic bacterium, Amycolatopsis methanolica, was purified to homogeneity. It is a trimeric enzyme with identical subunits (molecular mass 40 kDa) containing 6 atoms Zn/enzyme molecule. The factor is a heat-stable, low molecular-mass compound, which showed retention on an Aminex HPX-87H column. Inactivation of the factor occurred during manipulation, but activity could be restored by incubation with dithiothreitol. The identity of the factor is still unknown. It could not be replaced by thiol compounds or cofactors known to be involved in metabolism of C1 compounds. Of the aldehydes tested, only formaldehyde was a substrate. However, the enzyme showed also activity with higher aliphatic alcohols and the presence of the factor was not required for this reaction. Methanol was not a substrate, but high concentrations of it could replace the factor in the conversion of formaldehyde. Presumably, a hemiacetal of formaldehyde is the genuine substrate, which, in the case of methanol, acts as a factor leading to methylformate as the product. This view is supported by the fact that formate could only be detected in the reaction mixture after acidification. Inhibition studies revealed that the enzyme contains a reactive thiol group, being protected by the binding of NAD against attack by heavy-metal ions and aldehydes. Studies on the effect of the order of addition of coenzyme and substrate suggested that optimal catalysis required NAD as the first binding component. Substrate specificity and the induction pattern clearly indicate a role of the enzyme in formaldehyde oxidation. However, since FD-FA1DH was also found in A. methanolica grown on n-butanol, but not on ethanol, it may have a role in the oxidation of higher aliphatic alcohols as well. FD-FA1DH and the factor from A. methanolica are very similar to a combination already described for Rhodococcus erythropolis [Eggeling, L. & Sahm, H. (1985) Eur. J. Biochem. 150, 129-134]. NAD-linked, glutathione-dependent formaldehyde dehydrogenase (GD FA1DH) resembles FD-FA1DH in many respects. Since glutathione has so far not been detected in Gram-positive bacteria, FD-FA1DH could be the counterpart of this enzyme in Gram-positive bacteria. Alignment of the N-terminal sequence (31 residues) of FD-FA1DH with that of GD-FA1DH from rat liver indeed showed similarity (30% identical positions). However, comparable similarity was found with class I alcohol dehydrogenase from this organism and with cytosolic alcohol dehydrogenase from Saccharomyces cerevisiae, isozyme 1.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597191 TI - Dye-linked dehydrogenase activities for formate and formate esters in Amycolatopsis methanolica. Characterization of a molybdoprotein enzyme active with formate esters and aldehydes. AB - Cell-free extracts of methanol-grown Amycolatopsis methanolica contain dye-linked dehydrogenase activities for formate and methyl formate. Fractionation of the extracts revealed that the (unstable) activity for formate resides in membrane particles, while that for methyl formate belongs to a soluble enzyme that was purified and characterized. The enzyme, indicated as formate-ester dehydrogenase, appeared to be a molybdoprotein (4 Fe, 3 or 4 S, 1 Mo and 1 FAD were found for each enzyme molecule), with a molecular mass of 186 kDa and consisting of two subunits of equal size. Product identification suggests that the formate moiety in the ester becomes hydroxylated to a carbonate group after which the unstable alkyl carbonate decomposes into CO2 and the alcohol moiety. Based on structural and catalytic characteristics, the enzyme appears to be very similar to an enzyme isolated from Comamonas testosteroni [Poels, P. A., Groen, B. W. & Duine, J. A. (1987) Eur. J. Biochem. 166, 575-579] which was at that time considered to be an aldehyde dehydrogenase. Formate-ester dehydrogenase activity appeared to be present in several other bacteria. Possible roles for the A. methanolica enzyme in C1 dissimilation (oxidation of methyl formate to methanol and CO2 or a factor formate adduct to factor plus CO2) or in general aldehyde oxidation, are discussed. PMID- 1597192 TI - Substrate specificity of purified rabbit liver esterase ES-1. AB - 1. Substrate hydrolysis by two purified rabbit liver esterase-1 allozymes (ES-1A and ES-1B) was compared under conditions differing in substrate, pH and temperature. ES-1A and ES-1B activities had a similar pH and temperature dependency and similar thermal stability profile. 2. There were marked differences in specific activity of ES-1A and ES-1B. ES-1A hydrolysed procaine more rapidly than ES-1B, but was less active towards aspirin. The acetate and propionate esters of p-nitrophenyl were hydrolysed slower by ES-1A than by ES-1B. 3. The effect of substrate concentration on ES-1A activity did not comply with the Michaelis-Menten kinetics, which may be due to so-called substrate activation. 4. At identical substrate concentration, pH and temperature, selected artificial esters were better substrates for ES-1A than selected physiological substrates. Beta-Naphthyloctanoate was found to be a suitable substrate for ES 1A. 1,3-Dioctanoylglycerol was hydrolysed at a rate of only 2% of that of beta naphthyloctanoate. 5. With methyl, p-nitrophenyl, beta-naphthyl and 4 methylumbelliferyl esters as substrates, ES-1A activity is influenced by length and structure of the acyl moiety. Likewise, ES-1A activity is influenced by the nature of the alkyl moiety of acetate esters. With acetate and methyl esters, branched chains when compared with unbranched chains reduced the esterase activity of ES-1A. Elongation of the acyl moiety up to four or five C atoms gradually raised the velocity of methyl, p-nitrophenyl, and 4-methylumbelliferyl ester hydrolysis by ES-1A. A similar pattern was found for the length of the alkyl moiety of acetate esters. 6. The high degree of similarity between the observed substrate specificity of rabbit ES-1A and that reported earlier for rat ES-10, suggests that these two esterases have a common evolutionary origin. PMID- 1597193 TI - Rac1, a low-molecular-mass GTP-binding-protein with high intrinsic GTPase activity and distinct biochemical properties. AB - Rac1, a member of the family of low-molecular-mass GTP-binding proteins, functions in phagocytic leukocytes as a component necessary for activation of the respiratory burst. To characterize the biochemical properties of rac1, the protein was expressed as a fusion protein in Escherichia coli and purified to greater than 99% homogeneity by affinity chromatography. Rac1 protein bound maximally bound and hydrolyzed GTP under low free-Mg2+ concentrations. Under those conditions, (45 nm free Mg2+), purified rac1 exhibited a steady-state GTPase activity of 18 nmol.min-1.mg protein-1 (turnover number approximately 0.39 min-1 at 37 degrees C), which is 40-fold higher than H-ras. The high intrinsic GTPase activity of rac1 under low free Mg2+ was mainly due to an increased kcat, the rate constant for hydrolysis of bound GTP, which was 0.29 min-1 for rac1 vs 0.007 min-1 for H-ras (at 20 degrees C). Rac1 also released bound GDP faster than H-ras (koff.GDP = 1.02 min-1 for rac1 vs 0.33 min-1 for H-ras at 20 degrees C). In contrast, rac1 released bound guanosine 5'-[gamma-thio]triphosphate (GTP[S]) at a slower rate than H-ras (koff.GTP[S] approximately 0.04 min-1 for rac1 vs 0.31 min-1 for H-ras at 20 degrees C). Rac1 was a very good substrate for in vitro geranylgeranylation (C20) but not for farnesylation (C15), whereas the converse is true for H-ras. Surprisingly, rac1 was a very poor substrate for in vitro ADP-ribosylation by the C3 component of Clostridium botulinum toxin compared to rhoA. As a further characterization of rac1, a mutant was made in which the Thr115 was replaced by asparagine. This protein (referred to as [Thr115 ---Asn]rac1) contains the consensus amino acids of all four GTP-binding domains of H-ras. The koff.GDP of [Thr115----Asn]rac1 was reduced to that of H-ras, but [Thr115----Asn]rac1 exhibited essentially identical kcat (0.13 min-1 at 20 degrees C) and koff-GTP[S] (0.03 min-1 at 20 degrees C) values as the wild-type protein. Thus, the region(s) in rac1 which control the dissociation of GTP[S] (and presumably GTP) do not entirely coincide with those controlling GDP dissociation. Biochemical analysis of [Thr115----Asn]rac1 also suggests that the region responsible for the increased kcat of rac1 is not within the consensus amino acids of the four guanine-nucleotide-binding domains. PMID- 1597194 TI - (R)-lactyl-CoA dehydratase from Clostridium propionicum. Stereochemistry of the dehydration of (R)-2-hydroxybutyryl-CoA to crotonyl-CoA. AB - 1. A new two-step method for purifying component E II of lactyl-CoA dehydratase was developed. The source of the enzyme was Clostridium propionicum grown on either D,L-alanine or L-threonine. No difference in these preparations was observed whether during purification or by SDS/PAGE of the pure enzymes. Both preparations exhibited similar activities towards (R)-lactyl-CoA as well as towards (R)-2-hydroxybutyryl-CoA, the latter being the superior substrate. 2. Three species of (2R)-2-hydroxybutyrate labelled with 3H at C3 were prepared containing 96%, 37% and 63% of the 3H in the 3S-position. By incubation of these species with acetyl-CoA, propionate CoA-transferase and lactyl-CoA dehydratase 104%, 32% and 70% of the 3H, respectively, was release as 3HOH. The data indicate that stereospecific abstraction of the 3Si hydrogen of (2R)-2-hydroxybutyryl-CoA during the dehydration. 3. The identity of the product of the dehydration as crotonyl-CoA was established by the combined action of the enzymes crotonase and (S)-3-hydroxyacyl-CoA dehydrogenase. The results indicate that the elimination of water from (R)-2-hydroxybutyryl-CoA occurs in a syn mode. 4. All enzyme activities necessary for the conversion of L-threonine via (R)-2-hydroxybutyryl CoA to butyrate were detected in cell-free extracts of C. propionicum. 5. A new mechanism for the dehydration of lactyl-CoA is proposed. PMID- 1597195 TI - The role of Lys272 in the pyridoxal 5-phosphate active site of Synechococcus glutamate-1-semialdehyde aminotransferase. AB - Glutamate-1-semialdehyde (GSA) aminotransferase catalyzes transfer of the C2 amino group of glutamate 1-semialdehyde to the C1 position to yield the tetrapyrrole precursor 5-aminolevulinate. Based on spectrophotometric and steady state data, GSA aminotransferase is a B6-containing enzyme which uses a ping-pong bi-bi mechanism described for other aminotransferases. A putative active-site lysine at position 272 of Synechococcus GSA aminotransferase was replaced by Arg, Ile or Glu, and genes encoding the corresponding three site directed mutants were expressed in Escherichia coli. The catalytic competence of the resulting enzymes was determined. The similarity of the absorbance spectra of pyridoxal-P-treated forms of Lys272----Arg, Lys272----Ile, Lys272----Glu with free pyridoxal-P indicates that enzyme-bound pyridoxal-P does not form an internal aldimine in in these three site-directed mutants. Whereas Lys----Ile and Lys----Glu form only stable ketimines and aldimines with GSA and its analogues, addition of these compounds to the pyridoxamine-P and pyridoxal-P forms of Lys----Arg induces slow spectral changes, indicating the catalysis of a half-reaction with GSA, 4,5 dioxovalerate and 4,5-diaminovalerate. 5-Aminolevulinate apparently binds with both coenzyme forms of Lys272----Arg, however significant tautomeric rearrangement is only observed with the pyridoxal-P form. It is suggested that Lys272 is the covalent pyridoxal-P-binding site and that this catalytically active lysine residue channels the overall transamination reaction towards 5 aminolevulinate. The second-half reaction (4,5-diaminovalerate in equilibrium with 5-aminolevulinate) is possibly supported by the formation of an internal aldimine which correctly positions the C4 amino group of 4,5-diaminovalerate relative to the enzyme-bound pyridoxal-P. PMID- 1597196 TI - DNA-activated protein kinase in Raji Burkitt's lymphoma cells. Phosphorylation of c-Myc oncoprotein. AB - Autophosphorylation of a DNA-activated protein kinase (DNA-PK) in Raji Burkitt's lymphoma cells generated a band that corresponded to a phosphoprotein of about 300 kDa on SDS/PAGE. This band corresponds to a 300-350-kDa DNA-PK found previously in HeLa cells. In addition to the 300-kDa phosphoprotein, the band of a highly phosphorylated 58-kDa protein was detected by SDS/PAGE of partially purified DNA-PK preparations after the phosphorylation reaction in the presence of double-stranded DNA. This phosphoprotein was specifically immunoprecipitated by phosphoprotein nor detectable activities of other kinases, phosphorylated recombinant c-Myc proteins in the presence of DNA. The c-Myc phosphorylation by DNA-PK was markedly stimulated by relaxed, double-stranded DNA, but neither by single-stranded DNA nor by RNA. Phosphopeptide mapping and phosphoamino acid analysis indicated that DNA-PK phosphorylates c-Myc in vitro at several serine residues. PMID- 1597197 TI - Pneumonia in childhood: etiology and response to antimicrobial therapy. AB - A prospective eight-month study was carried out in 50 children admitted to hospital for radiologically confirmed community-acquired pneumonia. A potential causative agent of infection was identified in 44 (88%) cases. Using virus isolation, virus antigen detection and enzyme immunoassay serology, respiratory virus infection was diagnosed in 30 (60%) patients. Antibody assays for seven bacteria and antigen detection from serum and urine for Streptococcus pneumoniae produced evidence of bacterial infection in 31 (62%) cases. Streptococcus pneumoniae (38%), respiratory syncytial virus (30%) and Mycoplasma pneumoniae (20%) were the most common causative agents. A mixed infection was diagnosed in 25 (50%) episodes. Nine patients failed to respond to antibiotics within 24 h after onset of treatment. Three of them had a pure viral infection, three a mixed viral-bacterial infection, two a Mycoplasma pneumoniae infection mixed with other bacteria and one a pure Mycoplasma pneumoniae infection. All three Mycoplasma pneumoniae infections were initially treated with penicillin. PMID- 1597198 TI - Cross-reactive proteins of Borrelia burgdorferi. AB - The specificity of serological tests for Lyme borreliosis is impaired by cross reacting antibodies. In order to select antigens for more specific tests, specific and cross-reactive proteins of Borrelia burgdorferi must be identified. Therefore, to analyze cross reactions of Borrelia burgdorferi with other bacteria, rabbit immune sera against heterologous bacteria (Borrelia hermsii, Treponema pallidum, Treponema phagedenis, Leptospira interrogans (serogroup grippotyphosa), Neisseria meningitidis, Haemophilus influenzae, Yersinia enterocolitica (serotypes O3 and O9), Campylobacter jejuni, Listeria monocytogenes O1, Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium, Shigella flexneri and Legionella micdadei) were examined by Western blot using Borrelia burgdorferi as antigen. Broad cross reactivity was shown for Borrelia proteins of the 60-75 kDa range. Other broadly cross-reacting proteins were at the level of p40, p33 and two proteins in the range of 20 kDa. Some of the cross reactions were eliminated by absorption of the sera with Treponema phagedenis. The absorbed antibodies were directed mainly against bands at the level of p33 and bands of the 60 to 75 kDa range. Showing the lowest potential for cross reactivity, p100, p41, OspA and pC seem to be the most suitable antigens for serodiagnosis. In contrast to p100 and OspA, however, p41 and pC showed cross reactivity with immune sera against bacteria not belonging to the genus Borrelia. PMID- 1597199 TI - Comparison of polymerase chain reaction and chlamydiazyme for the detection of Chlamydia trachomatis in clinical specimens. AB - An attempt was made to improve laboratory diagnosis of Chlamydia trachomatis and to validate the Abbott Chlamydiazyme confirmatory test used at present by comparing the polymerase chain reaction (PCR) procedure and the Abbott enzyme immunoassay. A total of 275 routine clinical specimens representing a range of positive and negative findings by Chlamydiazyme were retested by PCR. The procedures demonstrated 99% concordance for specimens with optical density (OD) readings above the Chlamydiazyme cut-off of 0.1, but PCR was confirmed to be significantly more sensitive (p less than 0.025) for specimens with OD values between 0.05 and 0.09. Specimens in this range should be retested routinely by PCR. PMID- 1597201 TI - A pseudo-outbreak of Methylobacterium mesophilica isolated from patients undergoing bronchoscopy. AB - An unusual, slow growing, pink-pigmented gram-negative bacillus was isolated from bronchoscopy specimens of seven patients over a three-month period. The organism was identified as Methylobacter mesophilica. None of the patients were believed to be infected with Methylobacter mesophilica. The results of environmental cultures showed that the organism was present in tap water from the bronchoscopy room. PMID- 1597200 TI - Moraxella catarrhalis bacteremic pneumonia in adults: two cases and review of the literature. AB - Moraxella (formerly Branhamella) catarrhalis is a gram-negative coccus now recognized as one of the common pathogens in respiratory infections. Documented cases of bacteremic pneumonia due to this organism, however, have been a rarity. Two cases of Moraxella catarrhalis bacteremic pneumonia in immunosuppressed adult patients are reported. The clinical characteristics of these patients together with those of the seven adult and the six pediatric patients reported to date in the literature, are analyzed. All patients had an underlying condition and most were male. The mean age was 64.9 years. No adult patient had skin lesion, although purpuric rash was frequent in children. The overall morality rate was only 13.3%, in spite of the underlying diseases. In three patients the pneumonia was nosocomial. The seasonal recovery of Moraxella catarrhalis in respiratory infections is significantly increased during the late fall through early spring period. Because most strains are beta-lactamase positive, empiric use of penicillin, ampicillin or amoxicillin for this organism can no longer be recommended. PMID- 1597202 TI - Evaluation of a new commercial Clostridium difficile toxin A enzyme immunoassay using diarrhoeal stools. AB - A new, commercially available enzyme immunoassay for the detection of toxin A in stool specimens, the Premier Clostridium difficile Toxin A test (Meridian Diagnostics), was evaluated using 228 diarrhoeal stool specimens. Using a cytotoxin assay on HeLa cells as the reference method, this new test resulted in a sensitivity of 88% and a specificity of 95%. Using the presence or absence of a toxigenic strain in the stools as the reference method, the sensitivity was similar to that of the cytotoxin assay (71.7+ versus 70.5%) and the overall correlation was even better (89.4% versus 82%). The Premier Clostridium difficile Toxin A assay is rapid and easy to perform and is an excellent alternative to the usual toxin B assay. PMID- 1597203 TI - A rapid heat-resistant technique for presumptive identification of Salmonella on desoxycholate-citrate agar. AB - A caprylate esterase chromogenic test, which was considered to indicate positivity in 5 minutes if a bright colour appeared on the filter paper inoculum site to which one colony had been applied, was used to test 534 Salmonella, 535 other bacteria capable of growth on desoxycholate-citrate agar (DCA), and 517 non lactose fermenting colonies from stool cultures on DCA. It was found to be 100% sensitive for Salmonella, 99% specific, and more accurate than either direct antiserum agglutination or a urease test in these respects. The test kit could be stored at room temperature. PMID- 1597204 TI - Synergism of trimethoprim and ciprofloxacin in vitro against clinical bacterial isolates. AB - For the first time, the effects of combinations of trimethoprim and a fluoroquinolone (ciprofloxacin) against gram-positive and gram-negative bacterial isolates were evaluated in vitro. Synergism was found in 31% (fractional inhibitory concentration, FIC) and 33% (fractional bactericidal concentration, FBC) of 121 clinical isolates of various bacterial strains, most often in Escherichia coli, staphylococci, and enterococci. Antagonism occurred in 1% (FIC) and 3% (FBC). The combination of trimethoprim and ciprofloxacin merits further evaluation for potential usefulness as a clinical regimen. PMID- 1597205 TI - Influence of pefloxacin on microbial colonization resistance in healthy volunteers. AB - The influence of pefloxacin, 400 mg twice daily for ten days, on microbial colonization resistance was investigated in six healthy volunteers. In three volunteers impairment of colonization resistance was indicated by a significant increase in the faecal concentration of yeasts. In two of them, impairment of colonization resistance was confirmed by facilitation of colonization by a challenge strain of Klebsiella pneumoniae in the early post-treatment period. It is concluded that pefloxacin impairs colonization resistance in some volunteers. However, during pefloxacin therapy, overgrowth by aerobic bacteria is prevented by the very high antimicrobial concentration in faeces, and after therapy it is prevented by rapid restoration of colonization resistance. PMID- 1597206 TI - Effect of several antimicrobial agents on ciprofloxacin uptake by human neutrophils. AB - The effect of antimicrobial agent active against anaerobes, gram-positive cocci and fungi on the uptake of ciprofloxacin by human neutrophils (PMNs) was evaluated. In the presence of therapeutic extracellular concentrations of these agents, ciprofloxacin reached high intracellular concentrations [cellular-to extracellular ratio (C/E) greater than or equal to 2.9], this value being higher in the presence of amphotericin B (C/E 6.3 +/- 0.9). The intracellular penetration of ciprofloxacin was higher when PMNs were stimulated with opsonized zymosan (C/E greater than or equal to 5.6). In summary, none of the antimicrobial agents tested significantly impaired the uptake of ciprofloxacin by human PMNs. PMID- 1597207 TI - Susceptibility of anaerobic bacteria to tosufloxacin. AB - The in vitro activity of tosufloxacin against anaerobic cocci, Propionibacterium acnes, Clostridium perfringens, Clostridium difficile, Bacteroides fragilis, Bacteroides spp. and fusobacteria was determined by the agar dilution method. This activity was compared with that of ciprofloxacin, piperacillin, cefoxitin, imipenem, clindamycin, metronidazole and chloramphenicol. Tosufloxacin, imipenem, clindamycin, metronidazole and chloramphenicol were the most active agents tested. Tosufloxacin has an antibacterial activity that warrants investigation in clinical trials. PMID- 1597208 TI - Native valve endocarditis caused by Staphylococcus simulans. PMID- 1597209 TI - A new report of triclabendazole efficacy during invading phase fasciolasis. PMID- 1597210 TI - Detection of mycobacteria using the polymerase chain reaction. PMID- 1597211 TI - In vitro activity of antifungal azoles against Helicobacter pylori. PMID- 1597212 TI - In vitro susceptibility of Helicobacter pylori to nitecapone. PMID- 1597213 TI - Risk factors for ischaemic heart disease in a Greek population. A cross-sectional study of men and women living in the village of Spili in Crete. AB - We have established a research project in primary health care in Crete with the aim of surveying the cardiovascular risk profile of a defined 'low-risk' population. The study population comprised all men and women aged 15-79 years in the village of Spili (n = 445); the overall attendance rate was 77% (greater than or equal to 82% in those aged 45 years and above). In this cross-sectional study we found a high (44%) prevalence of smoking in men aged 45-64 years as well as a high alcohol intake (48% drank greater than or equal to 210 g of pure alcohol every week). Furthermore, there was a high cholesterol level (6.2 mmol.l-1), and a high prevalence of hypertension and diabetes. Against this background it is somewhat surprising that we did not find any signs of post-myocardial infarction in Spili men aged 63 and under. It is possible that positive factors, i.e. the closely knit social networks, the low unemployment rate, the hard water, and some of the dietary habits, e.g. the high consumption of olive oil, may counter balance the negative factors mentioned above. It is also possible that the low risk factors in the past explain the low incidence of myocardial infarction today, and that this will change in the years to come. PMID- 1597214 TI - Coronary response to diving in subjects with mild and severe left coronary artery disease. AB - The cold pressor test (CPT) is commonly used to determine the vasospastic origin of angina and to investigate the factors modulating coronary vasomotor tone. However, coronary vasoconstriction associated with this manoeuvre is often limited, particularly in patients with mild coronary atherosclerosis. To identify stimuli that can more powerfully constrict the coronary arteries we compared the effects on coronary blood flow (thermodilution) and vascular resistance (mean aortic pressure divided by coronary blood flow) of CPT (2 min) and diving (D, 45 s) in subjects with angiographically documented mild (n = 11) or severe (n = 11) left anterior descending coronary artery stenosis. In subjects with severe coronary artery stenosis the rate-pressure product increased to a similar extent with CPT and D. The latter stimulus, however, caused a more marked fall in coronary blood flow and a much more pronounced increase in coronary resistance as compared to CPT (+44 +/- 3.1% vs +19 +/- 1.6%, P less than 0.01). In the face of a similar increase in rate-pressure product, D caused a significant increase in coronary vascular resistance also in patients with mild coronary artery stenosis (less than or equal to 50%) in which CPT failed to induce any coronary vasoconstriction (+16 +/- 1.8% vs +0.3 +/- 1.3%, P less than 0.01). Thus, diving is a much more powerful coronary vasoconstrictor stimulus than CPT. It can thus replace CPT when an increase in coronary resistance is needed for diagnostic purposes or for investigating abnormalities in coronary vascular regulation. PMID- 1597215 TI - EEG arousal and cardiovascular reactivity in professional drivers: the glare pressor test. AB - Patterns of electroencephalographic (EEG) and polygraphically recorded cardiovascular (CV) reactivity to the glare pressor test (GPT) were compared in 19 healthy, young male professional drivers and eight non-driver controls. After the first headlight impulse, 15 drivers showed persistent blockade of spontaneous alpha activity or complete desynchronization. This was accompanied by a significant fall in digital pulse amplitude and a significant rise in diastolic blood pressure (BP) (7.3 +/- 9.5 mmHg). Most drivers recovered baseline alpha activity and showed milder diastolic BP and digital pulse changes after the final (5th) glare impulse. However, in two drivers this last glare stimulus elicited the most pronounced changes: in one case a rapid onset of ventricular extrasystoles and in the other, maximal rise in diastolic BP, together with a persistently desynchronized EEG. No significant effects of the GPT upon central and CV indices were found in the control group. These results indicate that drivers show cardiovascular hyperreactivity to the GPT, with strong central arousal as expected during night driving when an on-coming headlight can represent impending danger and the need for accurate and timely responses to avoid a collision. Once optimal stimulus parameters for routine application are determined, the glare pressor test with EEG and polygraphic recording will offer a clinically useful, standardizable method for evaluating the connection between central mechanisms and CV reactivity in professional drivers, a cohort of patients whose occupational activity epitomizes mentally stressful work, and who are at high cardiac risk. PMID- 1597216 TI - The interrelation between the monophasic action potential duration, cycle length and ischaemia in the human left ventricle. AB - Steady state monophasic action potentials were recorded from a single site in the left ventricular endocardium during incremental atrial pacing to the point of angina in 25 patients. Ischaemic areas of the left ventricle were documented using a perfusion marker (99mTc-MIBI) simultaneously with the action potential recording procedure. Recordings were obtained from an ischaemic area in 13 patients and from a non-ischaemic area in 12. A linear correlation between action potential duration and cycle length changes was demonstrated for both ischaemic and non-ischaemic zone recordings between cycle length changes of 750 and 428 ms. Ischaemia induced a shortening of the action potential duration significantly greater than that produced by cycle length changes (P less than 0.0001). Mean action potential duration shortening corrected for 100 ms change in cycle length for ischaemic zone recordings was 31.4 +/- 4.2 (SD) compared to 23.3 +/- 3.1 ms for non-ischaemic zone recordings. A range of values of action potential duration shortening in unit time was analysed for sensitivity and specificity for the detection of ischaemia. A value of 26.5 ms per 100 ms change in cycle length provided the optimum compromise with 88% sensitivity and specificity. Our data provide a means of employing the monophasic action potential duration to quantify early localized ischaemia in the presence of an alteration in cycle length. PMID- 1597217 TI - Ventricular ectopic activity in physically trained hypertensive subjects. AB - Exercise training is currently recommended in the management of mild hypertension, but the relationship between training and ventricular arrhythmias has never been investigated in hypertensive subjects. Forty hypertensive sportsmen were studied by means of 24-h ECG Holter monitoring and the results were compared with those obtained in 40 sedentary hypertensives, 40 normotensive sportsmen and 40 normotensive sedentary subjects. Among the hypertensive sportsmen 82.5% exhibited at least one ventricular extrasystole and 32.5% complex forms of ectopy, a prevalence higher than that observed in the sedentary hypertensives (50% and 17.5%; P = 0.002). In the normotensive sportsmen the prevalence of ventricular arrhythmias (62.5% and 22.5%) was lower than that in the hypertensive sportsmen, but the difference was not statistically significant. During a training session the prevalence of ventricular ectopy was similar in the two groups of trained individuals. Among the hypertensive sportsmen no correlation was found between the severity of ventricular arrhythmias and the degree of left ventricular hypertrophy and performance. The results of the present study suggest that exercise training may enhance left ventricular vulnerability in hypertensive subjects. Whether subjects who manifest complex ventricular arrhythmias should continue to train remains a matter for individual judgement. PMID- 1597218 TI - Preserved left ventricular function during supine exercise in patients after orthotopic cardiac transplantation. AB - Cardiac denervation may affect cardiovascular responses during exercise in patients after orthotopic cardiac transplantation. In 17 such patients, haemodynamic responses and left ventricular function were examined by radionuclide ventriculography during and after supine exercise, at an average of 17.1 +/- 2.6 months after surgery. Data were also obtained during 'volume loading' brought about by leg elevation before exercise. Results were compared with those of six normal controls. At rest, heart rate was significantly faster among transplant patients than among controls (P less than 0.0003). No significant inter-group differences in changes in cardiovascular parameters were found between the two groups during leg elevation. During exercise, heart rate in transplant patients rose at a significantly slower rate than controls (P = 0.0001), but similar increases in ejection fraction, stroke volume and cardiac output were observed among transplant patients and controls. Decline in heart rate (P = 0.0001), ejection fraction (P = 0.0007) and cardiac output (P = 0.0001) was significantly slower in transplant patients during recovery. Although there were differences in rates of increases in heart rate between transplant patients and controls during supine exercise, there were no inter-group differences in increases in cardiac output and ejection fraction and changes in haemodynamic responses and left ventricular volumes. PMID- 1597219 TI - Predicting cardiac mortality after uncomplicated myocardial infarction by exercise radionuclide ventriculography and exercise-induced ST segment elevation. AB - In 183 consecutive patients with recent, uncomplicated myocardial infarction, the following variables were associated with 4-year cardiac death: haemodynamic decompensation with exercise (P = 0.01), left ventricular ejection fraction at rest (P = 0.004) and at peak exercise (P = 0.003), persistent ST segment elevation at rest in the area of infarction = (P = 0.004), exercise-induced ST segment elevation (P = 0.02), and late aneurysmal evolution (P = 0.01). Exercise left ventricular ejection fraction was the sole variable selected by Cox regression analysis as an independent predictor of cardiac death. In 40 patients with ST segment elevation at rest, left ventricular ejection fraction was 42 +/- 17% at rest and 40 +/- 18% at peak exercise, versus 52 +/- 12% and 52 +/- 14% in the remaining patients (both P less than 0.01). Among these 40, 16 (all with anterior infarction) also had exercise-induced ST segment elevation; their ejection fraction was 32 +/- 13% at rest, 30 +/- 13% during exercise, versus 53 +/- 15% and 53 +/- 15% in 129 patients with no ST segment elevation either at rest, or during exercise (both P less than 0.01). The 4-year risk of death was 20% in the former 40 patients, 36% in the latter 16, while in the complete absence of ST segment elevation, such risk was 3%. All 14 patients with ST segment elevation only during exercise were alive after 4 years: their left ventricular ejection fraction was 47 +/- 12% at rest, 45 +/- 13% with exercise. ST segment elevation was associated with late aneurysmal evolution but not with exercise-induced ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597220 TI - Excimer laser coronary angioplasty: experience with a prototype multifibre catheter in patients with stable angina pectoris. AB - Percutaneous excimer laser coronary angioplasty (ELCA) was performed in a first group of 20 patients with stable angina pectoris caused by significant coronary stenosis, and long-term follow-up was evaluated. Prototype 4 to 5.5 French multifibre catheters with 18-20 quartz fibres of 100 microns diameter, concentrically arranged around a central lumen for taking up a guide wire, were coupled to a commercial XeCl excimer laser. Energy was delivered at a wavelength of 308 nm with a pulse duration of 60 or 120 ns. Operating at a repetition rate of 20 Hz, mean energy transmission was 13.4 +/- 6.8 mJ per pulse. In all but one patient the lesion could be passed by the catheter. Percent diameter stenosis decreased from 77.1 +/- 10.8% to 53.1 +/- 11.8% after ELCA. Complications were frequently observed, intracoronary thrombus formation in eight instances, dissection in six patients and spasm in five cases, causing total vessel occlusion in five procedures. All complications could be managed efficaciously by thrombolytic and vasodilating drugs and/or balloon angioplasty. Subsequent PTCA was performed in case of complication or insufficient stenosis reduction after ELCA in 18 patients with adequate results (residual stenosis, 28.5 +/- 10.2%). Long-term follow-up angiography, which could be performed in 16 of 19 laser treatments, demonstrated significant restenosis in only three patients. Our preliminary results suggest that, using ELCA, ablation of atherosclerotic lesions is feasible in most cases. However, compared with PTCA, stenosis reduction is significantly less, and the acute complication rate is much higher. Thus, further improvements of the catheter system are necessary in order to realize the advantages of excimer laser ablation, which can be demonstrated by experimental studies. PMID- 1597221 TI - Doppler haemodynamic profiles of clinically and echocardiographically normal mitral and aortic valve prostheses. AB - Doppler echocardiographic studies were performed in 380 consecutive patients with 415 normally functioning artificial valves to establish normal Doppler characteristics for each type of prostheses used in our institution, with particular reference to Starr-Edwards valves, and to serve as control studies for future assessment. None of the patients were in heart failure at the time of the study. Peak transaortic velocities (m.s-1) were higher and effective orifice areas (cm2) smaller in mechanical valves as a whole, when compared with bioprostheses (P less than 0.01); 2.7 +/- 0.7 and 1.4 +/- 0.55 for Starr-Edwards, 2.7 +/- 0.6 and 1.5 +/- 0.6 for Bjork-Shiley, 1.8 +/- 0.1 and 1.5 +/- 0.6 for Duromedics and 1.5 +/- 0.06 and 2 +/- 0.12 for bioprostheses, respectively. In the mitral position, the average peak diastolic velocities (m. s-1) and pressure half-times (ms) were higher in mechanical valves, but there was a large overlap between the various types and sizes of prostheses (P = NS); 1.6 +/- 0.3 and 98 +/ 25 for Starr-Edwards, 1.4 +/- 0.3 and 88 +/- 26 for Bjork-Shiley, 1.8 +/- 0.1 and 75 +/- 5 for Duromedics and 1.5 +/- 0.3 and 90 +/- 20 for bioprostheses, respectively. There was an inverse relation between valve size and pressure halftime for Starr-Edwards prostheses (P less than 0.01). Doppler flow characteristics in mechanical valves where similar in patients with normal and dysfunctioning prostheses. Valvular or myocardial dysfunction could best be ascertained when early postoperative studies were available for comparison.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597222 TI - Ascending aortic Doppler velocity and the prediction of exercise capacity in post infarction left ventricular dysfunction. AB - A system to improve analysis of the aortic pulsed Doppler velocity signal has been developed and used to study cardiac performance during a 4 min, 25 W incremental stage supine bicycle exercise to exhaustion. Twenty-two male subjects with stable chronic ischaemic heart disease were studied (15 with NYHA class II/III heart failure, and seven age-matched class I subjects). None had evidence of reversible ischaemia. Peak velocity (PV) from the intensity weighted mean velocity profile, early acceleration (eA) and stroke distance (SD) were all significantly lower at rest in class II/III compared to class I. For the change from rest to 50 W, PV did not alter, eAC increased significantly (P less than 0.05) and to a similar extent in both groups (18.6% class II/III vs 16.4% class I) and SD was reduced from 7.8 to 5.9 in class II/III (P less than 0.01) but did not change in class I (12.4 vs 11.8, ns). There was also a greater increase in heart rate (HR) in class II/III subjects (P less than 0.05). The duration of exercise was correlated with resting PV (r = 0.48, P less than 0.025) but was correlated best with the change in blood momentum (PV x Stroke volume x HR) between rest and peak exercise (r = 0.80, P less than 0.001). Thus Doppler velocimetry can give quantitative information on the response to exercise which discriminates between grades of ventricular dysfunction and is predictive of exercise capacity. PMID- 1597223 TI - Transient ischaemia refractory to conventional medical treatment in unstable angina: angiographic correlates and prognostic implications. AB - Complex stenosis morphology is frequently seen in patients with unstable angina. However, its relation to transient myocardial ischaemia and clinical outcome has not been adequately elucidated. We studied 86 patients admitted to the Coronary Care Unit for unstable angina; all patients underwent ECG Holter monitoring during the first 2-4 days, while receiving intensive triple drug treatment. Coronary angiography and subsequent analysis of the ischaemia-related artery were performed within 12 days of admission. Patients were grouped according to their angiographic features: 45 showed complex coronary morphology (CM: 29 eccentric stenosis with irregular borders or overhanging edges; 16 intracoronary thrombus), 11 had documented coronary spasm as well as moderate atherosclerosis (CS), seven had left main coronary artery disease, and the remaining 23 patients showed regular and smooth morphology of coronary stenosis (RM). At admission, transient myocardial ischaemia (TMI) was greater in patients with CM (85 +/- 60 min .24 h 1) than in those with RM or CS (33 +/- 26 min .24 h-1; P less than 0.005). After 3 days of full medical treatment TMI decreased in all groups, but 34/45 patients with CM and 9/34 with RM or CS still showed residual ischaemia (greater than 0 min .24 h-1): 76% vs 26%, P less than 0.02. Follow-up was obtained at hospital discharge and after 1 year in all patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597224 TI - The importance of tricuspid valve structure and function in the surgical treatment of rheumatic mitral and aortic disease. AB - A significant proportion of individuals with rheumatic disease have tricuspid valve involvement which may be clinically important and alter the medical or surgical approach to treatment. Therefore 50 patients with rheumatic left-sided valvular lesions who were referred for operative treatment were studied. Thirty patients had angiographically significant tricuspid regurgitation (group I) and 20 had a competent tricuspid valve (group II). Pre-operative cardiac assessment included Doppler echocardiography and contrast ventriculography. Patients with tricuspid regurgitation more commonly had mitral valve disease or combined mitral and aortic valve lesions, (P less than 0.001) and were more likely to have atrial fibrillation than those without tricuspid regurgitation (P less than 0.001). Pulmonary arterial systolic and mean right atrial pressures were higher in group I (both P less than 0.01). A close relationship was found between the angiographic and Doppler assessment of the degree of tricuspid regurgitation (P less than 0.01). Doppler-derived measurement of the right ventricular-right atrial systolic pressure difference correlated well with the systolic trans tricuspid pressure difference measured at cardiac catheterization (y = 0.7x + 22, r = 0.67, P less than 0.001) and the pulmonary arterial systolic pressure (y = 0.8x + 27, r = 0.71, P less than 0.001). Rheumatic involvement of the tricuspid valve identified by pre-operative echocardiography was confirmed in five patients at surgery. Of the 13 patients with functional tricuspid regurgitation at operation, only two had been diagnosed as having organic disease by echocardiography. Furthermore, in all 18 cases where Doppler suggested grade 3 or 4+ tricuspid regurgitation, surgical repair or replacement of the valve was performed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597225 TI - Septal rupture after myocardial infarction: is very early surgery really worthwhile? AB - Despite numerous publications, mostly with small patient populations, the management of post-infarct septal rupture is still not well defined. Although urgent surgery appears to be the therapy of choice it is still unclear whether surgery very early after septal rupture in patients with severe haemodynamic compromise salvages a significant number of patients. In this paper we present the data from a large population of consecutive patients with post-infarct septal rupture from one cardiac centre. From 1980 through 1989, 108 patients with post infarct septal rupture were seen at this Regional centre of whom 81 had operative repair; 43 (53%) of these survived the early postoperative period. Of 32 patients with cardiogenic shock who had surgery, early operative mortality in those operated on within 48 h of rupture was 90% (18/20) compared with 33% (4/12) in those operated on later (P less than 0.001). All survivors with pre-operative shock had intra-aortic balloon counter-pulsation before operation. Concomitant coronary artery bypass grafting was not associated with improved survival in our patients. Three patients survived long-term without operation. Analysis of population statistics suggest that approximately 270 patients with post infarction septal rupture were not transferred from peripheral hospitals to the Regional Cardiothoracic Centre for assessment during this decade. PMID- 1597226 TI - Myocardial contrast echocardiography: influence of ischaemia and hyperaemia in an animal model. AB - To evaluate changes in myocardial contrast echocardiography during ischaemia and hyperaemia, contrast studies were performed in 16 open chest dogs. Time-intensity curves were generated using videodensitometry after contrast injections to demonstrate ischaemic and non-ischaemic areas of interest during a wide range of coronary blood flow levels. For each time-intensity curve, the peak contrast intensity (PCI), washout halftime (T1/2) and area under the curve (AUC) were calculated. PCI and AUC decreased significantly only with severe ischaemia (90% or more reduction in flow), and increased significantly with hyperaemia of more than 2.5 times baseline flow. Both ischaemia and hyperaemia were found to prolong the T1/2. There was only a moderate linear correlation between the magnitude of hyperaemia and myocardial contrast echocardiographic parameters. There was significantly less increase in myocardial contrast echocardiographic parameters during hyperaemia in segments supplied by a stenosed coronary artery. PMID- 1597227 TI - Evaluation of coronary flow reserve using myocardial contrast echocardiography in humans. AB - To evaluate the applicability of myocardial contrast echocardiography for the assessment of coronary blood flow reserve, 21 consecutive patients undergoing coronary angiography were studied. Only patients with a single left anterior descending lesion or normal coronary angiogram were included. Intracoronary injections of sonicated albumin were performed before and after the administration of intracoronary papaverine. Good quality studies at baseline and after the administration of papaverine were obtained in 14 of 21 patients. Ten patients had a significant (greater than 75%) single left anterior descending lesion and four had normal or insignificant lesions (70% or less stenosis) in the left anterior descending coronary artery. Time-intensity curves for the left anterior descending coronary artery region of interest were generated and then the peak contrast intensity (PCI), washout half-time (T1/2) and the area under the curve (AUC) were calculated. The post-papaverine increases in PCI and in the AUC, compared to baseline, were 55 +/- 22% and 102 +/- 14% in the four patients with 70% or less left anterior descending diameter stenosis serving as a control group and 3 +/- 25% and 40 +/- 10%, respectively, in the 10 patients with significant left anterior descending coronary artery disease (mean +/- 1 SD, P less than 0.01). In patients with normal coronary arteriography T1/2 increased after intracoronary injection of papaverine. In patients with severe lesions, either an increase or a decrease in T1/2 was observed. Significant left anterior descending coronary artery stenosis associated with impaired coronary blood flow reserve can be detected by failure of myocardial contrast echocardiographic parameters to increase after injection of papaverine. Mild and transient side effects were noted in three patients. PMID- 1597228 TI - Effect of cicletanine on reperfusion-induced arrhythmias and myocardial ion contents: a comparison with furosemide. AB - We studied the effects of cicletanine, a furopyridine antihypertensive drug, and furosemide, a loop diuretic, on ventricular arrhythmias, such as sustained ventricular fibrillation (VF) and ventricular tachycardia (VT), and myocardial ion content in Langendorff rat hearts subjected to 30 min global ischaemia then 10 min reperfusion. Myocardial Na+, K+, Ca2+ and Mg2+ concentrations were measured by washout technique and atomic absorption spectrophotometry before and after ischaemia and reperfusion. Drugs were either perfused (acute treatment) or orally gavaged daily to the rats for 14 days before isolation of their hearts (chronic treatment). Under in vitro conditions 10(-5), 3 x 10(-5), 10(-4) or 3 x 10(-4) M of cicletanine reduced the incidence of sustained VF and VT from the control values of 91% and 100% to 83% and 100%, 50% (P less than 0.05) and 67%, 33% (P less than 0.01) and 50% (P less than 0.05), 25% (P less than 0.01) and 41% (P less than 0.05), respectively. Chronic treatment with 3, 10, 30 or 100 mg.kg 1.day-1 of cicletanine also resulted in a dose-dependent anti-arrhythmic effect. Neither acute (10(-5), 3 x 10(-5) and 10(-4) M) nor chronic furosemide treatment (3, 10 and 30 mg.kg-1.day-1) influenced the incidence of arrhythmias. Acute treatment with cicletanine or furosemide did not change myocardial ion concentrations, in non-ischaemic hearts, while chronic treatment with 30 mg.kg 1.day-1 furosemide significantly reduced myocardial Na+, K+ and Mg2+ content and increased Ca2+ concentration. Both acute and chronic cicletanine treatments attenuated ischaemia/reperfusion-induced myocardial Na+ and Ca2+ gains and K+ loss, while furosemide did not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597229 TI - Gallopamil and diltiazem: a double-blind, randomized, cross-over trial in effort ischaemia. AB - The aim of this study was to evaluate the efficacy and possibly the mechanism of action of gallopamil and diltiazem in a double-blind crossover trial in patients with effort ischaemia. Twenty male patients (mean age 57 +/- 6 years) with documented coronary atherosclerosis and exercise-induced ischaemia (ST depression greater than or equal to 0.15 mV) completed the study, which consisted of four 7 day periods. At the end of each period a multistage bicycle exercise stress test was performed under placebo (first and third periods) and randomly under gallopamil (50 mg t.i.d.) or diltiazem (90 mg t.i.d.) in the second and fourth periods. Both drugs significantly increased time to ischaemia (0.15 mV ST depression) as compared to placebo, from 7.9 +/- 1.7 min to 8.9 +/- 1.1 min (diltiazem) and 9.1 +/- 1.6 min (gallopamil) with no significant difference between the two drugs, and reduced the maximal extent of ST shift from 0.18 +/- 0.08 mV to 0.13 +/- 0.04 mV (diltiazem) and 0.12 +/- 0.05 mV (gallopamil). Analysis of the results from the whole population showed that the beneficial effect did not appear to be related to any specific parameter. Individual analysis showed that 13/20 patients under gallopamil and 13/20 under diltiazem increased time to ischaemia, while this was unchanged or reduced in the remainder. A positive correlation between changes in time to ischaemia and changes in rate x pressure product at ischaemia was found in both those administered gallopamil (R 0.80, P less than 0.01) and diltiazem (R 0.65, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597230 TI - Absence of nitroglycerin-induced heparin resistance in healthy volunteers. AB - A previously described nitroglycerin-induced heparin resistance could not be verified by in-vitro experiments or in a randomized, double-blind, crossover trial in healthy volunteers. A clinically relevant attenuation of the anticoagulant effect of a heparin bolus (40 U.kg-1) by a concomitant infusion of nitroglycerin (100 micrograms.min-1) was absent. Activated partial thromboplastin time was not significantly different under nitroglycerin infusion as compared to placebo after heparin injection. Concentrations and activities of antithrombin III and heparin cofactor II remained unchanged during nitroglycerin infusion. An interaction of these two frequently combined drugs in patients with active thromboembolic disease or after a prolonged concomitant intravenous administration cannot be ruled out. Since this is of clinical importance, further studies must clarify a possible nitroglycerin-induced heparin resistance. PMID- 1597231 TI - Diagnosis of cerebral arteriovenous malformation by colour Doppler examination. AB - A newborn presented in congestive cardiac failure, and colour Doppler ultrasonography confirmed a large aneurysm of the vein of Galen. The two dimensional cranial ultrasound appearance was not diagnostic but colour Doppler examination highlighted the marked vascular abnormalities. The colour Doppler appearances were dramatically altered following coil embolisation of the vein of Galen. Colour Doppler examination is the technique of choice for diagnosis and follow-up of this unusual condition. PMID- 1597232 TI - Transoesophageal echocardiography in the diagnosis of cor triatriatum; incremental value of colour Doppler. AB - Cor triatriatum sinistrum is a rare congenital cardiac abnormality often accompanied by other malformations. Transthoracic echocardiography does not always define the membrane and associated abnormalities; so, transoesophageal colour Doppler echocardiography was used to visualize intra-atrial blood flow through the intra-atrial membrane in a patient in whom the membranous orifice could not be seen by precordial echocardiography. There was no anomalous pulmonary venous drainage or associated atrial septal defect. PMID- 1597233 TI - Sudden death during pregnancy in hypertrophic cardiomyopathy. AB - A 27-year-old asymptomatic woman became pregnant 6 months after a diagnosis of hypertrophic cardiomyopathy and was well until 28 weeks' gestation when she died suddenly while running up stairs. The potential pathophysiological mechanisms of sudden death during pregnancy in hypertrophic cardiomyopathy, as well as the diagnostic and therapeutic implications, are discussed. PMID- 1597234 TI - Annular submitral left ventricular aneurysm. AB - Annular subvalvular aneurysms have been reported rarely in Caucasian individuals. We describe the case of a white man who had an asymptomatic annular submitral left ventricular aneurysm diagnosed during the diagnostic work-up of cervical lymphadenopathies. Our case is unique because of its occurrence in a Caucasian and its characteristic radiological features. PMID- 1597235 TI - Cardiac failure secondary to hypocalcaemia of nutritional osteomalacia. AB - A 41-year-old Asian woman presented with mild congestive cardiac failure, initially controlled with a small dose of diuretic. Subsequently there was a marked deterioration in her condition with severe cardiac failure resistant to treatment. At this time biochemistry revealed a hyperphosphataemic variety of osteomalacia. Her cardiac failure improved promptly on correcting the hypocalcemia. Although hypocalcaemia is a recognised cause of cardiac failure it has not been described in privational osteomalacia. PMID- 1597236 TI - A case of anomalous origin of the left anterior descending coronary artery from the right coronary artery. PMID- 1597237 TI - ERASMUS(European Communities Actions Schema for the Mobility of University Students) and nuclear medicine. PMID- 1597239 TI - Retrospective evaluation of the dose received by the ovary after radioactive iodine therapy for thyroid cancer. AB - In an earlier study, we evaluated the frequency of clinical manifestations of ovarian insufficiency after radioiodine therapy for thyroid cancer. We were thus led to consider the dose received by the ovary (DRO) during these treatments. In the literature, this dose is expressed as a function of the activity administered. However, in our study, the disorders were not correlated with the activity administered. Faced with this discrepancy, we have attempted to establish a dosimetric model using the parameters available for each patient. The results obtained show that besides the activity administered, which plays a role, morphological and kinetic factors specific to each individual have an importance that cannot be ignored when addressing this problem. PMID- 1597238 TI - Physical assessment of the GE/CGR Neurocam and comparison with a single rotating gamma-camera. AB - The GE/CGR Neurocam is a triple-headed single photon emission tomography (SPET) system dedicated to multi-slice brain tomography. We have assessed its physical performance in terms of sensitivity and resolution, and its clinical efficacy in comparison with a modern, single rotating gamma-camera (GE 400XCT). Using a water filled cylinder containing technetium-99m, the tomographic volume sensitivity of the Neurocam was 30.0 and 50.7 kcps/MBq.ml.cm for the high-resolution (HR) and general-purpose (GP) collimators, respectively; the corresponding values for the single rotating camera were 7.6 and 12.8 kcps/(MBq/ml)/cm. Tomographic resolution was measured in air and in water. In air, the Neurocam resolution at the cente of the field-of-view (FOV) is 9.0 and 10.7 mm full width at half-maximum (FWHM) with the HR and GP collimators, respectively, and is isotropic in the three orthogonal planes; the resolution of the GE 400XCT with 13 cm radius of rotation is 10.3 and 11.7 mm, respectively. For the Neurocam with the HR collimator, the transaxial FWHM values in water were 9.7 mm at the centre and 9.5 mm radial (6.6 mm tangential) at 8 cm from the centre. The physical characteristics of the Neurocam enable the routine acquisition of brain perfusion data with technetium-99m hexamethyl-propylene amine oxime (99mTc-HMPAO) in about 14 min, yielding better image quality than with a single rotating camera in 40 min. PMID- 1597240 TI - Estimation of organ input function and plasma clearance from the cardiac curve in dynamic scintigraphy. AB - A theoretical description of the relationship between the count rate detected in the cardiac region of interest and the arterial organ input function in dynamic scintigraphy is presented. It is shown that, provided the time-activity curve for the heart is corrected for extra-cardiac and unlabelled activity, it is proportional to the arterial organ input over both the first-pass and equilibrium phases of the passage of an intravenously injected radiopharmaceutical. A practical example demonstrating the value and validity of correcting the cardiac curve in dynamic radio colloid scintigraphy is described. Estimates of the colloid clearance rate to reticuloendothelial sites using the cardiac curve without correction were significantly lower (mean 0.085/min) than those derived from the liver uptake curve (mean 0.213/min). However, corrected cardiac curve clearance rates (mean 0.225/min) were not significantly different from the liver ones. Also, the corrected cardiac curve clearance values correlated linearly with liver curve values (correlation coefficient 0.89, standard error of the estimate 0.021/min), whereas the uncorrected values showed no significant correlation. Thus, correction of the cardiac curve gave clearance rate values that were both more accurate and more precise than those obtained without correction. PMID- 1597241 TI - Regional observer performance variation in the evaluation of gated cardiac blood pool studies. AB - Receiver operating characteristic (ROC) analysis demonstrated that regional variations of sensitivity exist in the detection of wall motion abnormality in cardiac blood pool imaging studies. The observer response is significantly better in the apex than either the septum or posterolateral wall segments. The observer errors tend to be false-negative in the posterolateral wall segment and false positive in the other two segments. Image presentation can make a significant difference to the overall sensitivity, and the monochrome cine-sequence performed best in this study. PMID- 1597242 TI - A comparison of maximal exercise and dipyridamole thallium-201 planar gated scintigraphy. AB - Both symptom-limited maximal exercise and intravenously given dipyridamole stress (0.56 mg/kg over 4 min with a 2 min walk) gated thallium scans were performed in 22 patients undergoing coronary arteriography for the assessment of chest pain. All scans were acquired gated to the electrocardiogram in 3 projections and were reported for the presence and extent of defects in 5 myocardial segments in each view. In addition, left and right ventricular myocardial uptake and estimates of right and left lung and liver to left ventricular uptake were assessed relative to the injected dose of thallium-201. Overall, 190/310 segments were abnormal with exercise compared with 169/310 with dipyridamole. Segments were scored greater in extent in 90/310 cases with exercise, compared with 46/310 in which the defect was more extensive with dipyridamole (P less than 0.0005). Non attenuation corrected percentage myocardial thallium uptakes were similar for both stresses: anterior percentage uptakes, 0.785% +/- 0.230% with exercise versus 0.870% +/- 0.217% with dipyridamole (NSD). Left and right lung and liver to left ventricle ratios were all significantly higher with dipyridamole than with exercise (1.587 +/- 0.408 versus 1.446 +/- 0.518, P less than 0.02; 1.78 +/- 0.479 versus 1.46 +/- 0.502, P less than 0.002; 2.598 +/- 0.788 versus 1.265 +/- 0.386, P less than 0.001, respectively). High right and left lung uptakes with dipyridamole were strongly correlated with high exercise values (r = 0.756, P less than 0.001; r = 0.809, P less than 0.001). The liver uptake was weakly correlated between the 2 different stress tests (r = 0.483, P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597243 TI - Serial change of iodine-123 metaiodobenzylguanidine (MIBG) myocardial concentration in patients with dilated cardiomyopathy. AB - Serial change of the metaiodobenzylguanidine iodine-123 (123I-MIBG) myocardial concentration was investigated in patients with dilated cardiomyopathy (DCM). Eight DCM patients and 6 control subjects were examined. After the injection of thallium-201 and 123I-MIBG, planar chest images were obtained simultaneously for both tracers in every 30-60 min over 5 h. Serial changes of myocardial uptake ratio (MUR) were compared for both tracers. In DCM, the initial MUR of 123I-MIBG did not differ significantly from that of the controls. The washout of 123I-MIBG from the myocardium, however, was significantly increased in DCM. In particular, the decrease in the early phase (15-45 min) was significantly larger in DCM than in the controls (21.2% +/- 7.5% vs. 5.3% +/- 4.0%, P less than 0.01), showing a significant negative correlation with the left ventricular ejection fraction (r = -0.72 P less than 0.05). For 201Tl, neither the initial MUR nor the washout rate different significantly between the two. Thus, an early rapid decrease of the 123I-MIBG myocardial concentration might characterize DCM and reflect the severity of this disease. PMID- 1597244 TI - Technetium-99m hexamethylpropylene amine oxime single photon emission tomography in febrile convulsions. AB - We report our initial experience with technetium-99m hexamethyl propylene amine oxime (99mTC-HMPAO) brain single photon emission tomography (SPET) in the investigation of 19 children presenting with febrile convulsions. Two patients with complex febrile convulsions showed focal SPET lesions contralateral to the neurological deficit. However, in 9 out of 17 patients with simple febrile convulsions, focally disturbed perfusion was shown. In 4 out of 6 patients with electroencephalogram (EEG) abnormalities on admittance, SPET revealed at least 2 focal lesions. The temporofrontal region was the one most commonly involved. The SPET findings presented here also suggest a temporal relationship with the febrile convulsions, with markedly fewer lesions if examined after 12 days. In our initial experience, perfusion SPET did not show any particular pattern helpful in the differential diagnosis of the child presenting with febrile convulsions. Physiopathologically, our findings may support the hypothesis that brain tissue is regionally more vulnerable to fever, in patients presenting with febrile convulsions. PMID- 1597246 TI - A review of the scientific highlights at the European Association of Nuclear Medicine Congress, Vienna 1991. PMID- 1597245 TI - Cortical perfusion response to an electrical stimulation of the auditory nerve in profoundly deaf patients: study with technetium-99m hexamethylpropylene amine oxime single photon emission tomography. AB - Brain activation procedures associated with single photon emission tomography (SPET) have recently been developed in healthy controls and diseased patients in order to help in their diagnosis and treatment. We investigated the effects of a promontory test (PT) on the cerebral distribution of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) in 7 profoundly deaf patients, 6 PT+ and one PT-. The count variation in the temporal lobe was calculated on 6 coronal slices using the ratio (Rstimulation-Rdeprivation)/Rdeprivation where R = counts in the temporal lobe/whole-brain count. A count increase in the temporal lobe was observed in all patients and was higher in all patients with PT+ than in the patient with PT-. The problems of head positioning and resolution of the system were taken into account, and we considered that the maximal count increment was related to the auditory cortex response to the stimulus. Further clinical investigations with high-resolution systems have to be performed in order to validate this presurgery test in cochlear implant assessment. PMID- 1597248 TI - Inflammation imaging with technetium-99m-HIG. PMID- 1597247 TI - Rest thallium-201 myocardial perfusion imaging in a patient with leukaemic infiltration of the heart. AB - Despite the high incidence of leukaemic infiltration of the heart, only 8 cases of atrioventricular block due to leukaemia have been reported in the literature. Improvement in the heart block associated with disappearance of the leukaemic infiltrate has not been reported. A rest thallium-201 study was used in a 65-year old man to demonstrate leukaemic infiltration of the heart which was associated with complete heart block. After chemotherapy, when the tumour burden was reduced and the leukaemia in remission, his heart block resolved, and a follow-up thallium scan was normal. PMID- 1597249 TI - Interaction of interleukin 2 and interleukin 4 during LAK cell generation. AB - Immunoregulatory lymphokines IL-2 and IL-4 produced by IL-2- and IL-4-cDNA transformed somatic cells were used for LAK cell generation. The cytolytic effect of LAK cells activated for 3 days with IL-2 and measured by 51Cr release of three types of target cells, YAC-1 (NK-sensitive), C1498 (NK-resistant) and X63-Ag8.563 (plasmocytoma cell line utilized for insertion of the IL-2 and IL-4 genes), was significantly depressed by adding IL-4 during the activation period. PMID- 1597250 TI - Production of transgenic mice from DNA-injected embryos cryopreserved by vitrification in microdrops. AB - Transgenic mice were produced from DNA-injected embryos stored for 2 to 30 days in liquid nitrogen. Of the 500 zygotes collected from (C57BL/6 x CBA)F1 mice, 363 (73%) survived DNA injection into pronuclei and 246 (82%) morphologically normal 4- and 8-cell embryos were flushed from temporary recipients 48 h later. Of the 200 DNA-injected 8-cell embryos cryopreserved by vitrification in microdrops, 194 (97%) were recovered and 188 (94%) embryos were intact one hour after thawing. Of the 50 DNA-injected and frozen/thawed embryos, 48 (96%) developed to morulae or blastocysts within 30 h of in vitro culture. Transfer of 100 DNA-injected and cryopreserved 8-cell embryos into 20 day-1 recipients resulted in 47 young born. Two mice were transgenic. PMID- 1597251 TI - A technique to examine cock sperm chromosomes using zona-free hamster eggs. AB - For the first time the visualization of cock sperm chromosomes using zona-free hamster eggs was described. Different variants of egg treatment were tested: varying the duration of incubation of eggs with spermatozoa from 5-6 to 20 h and the cytostatic treatment (colchicine) from 35 min to 9 h, varying the concentration of colchicine from 0.4-400 micrograms/ml and the hypotonic treatment with 0.1% and/or 1.0% sodium citrate or with distilled water from 2-5 to 12 min. In all variants sperm penetration was found, with changes in the head of sperm and the formation of pronucleus but there was no breakdown of the pronuclear envelopes. Only experiments, in which eggs were incubated without colchicine, were successful. PMID- 1597252 TI - Validity of delayed-type hypersensitivity and graft-versus-host reaction in testing of immunomodulators. AB - Assessment of cell-mediated immunity (CMI) is an integral part of preclinical studies of pharmaceuticals and xenobiotics. Even if several tests to determine CMI are available, their interpretation is fraught with uncertainty whether identical results can be expected for each of these particular tests after the challenge with different immunomodulatory substances. This dilemma has been addressed by investigating the changes in two basic tests of CMI in vivo, i.e. delayed-type hypersensitivity (DTH) to sheep red blood cells and regional graft versus-host reaction (GVHR), after the challenge with several immunomodulators. Both immunosuppressive modifiers (monoclonal anti-Thy 1, 2 antibody, cyclophosphamide, dexamethasone, methotrexate) and immunostimulatory agents (lipopolysaccharide, double-stranded RNA, thymostimulin, adamantylamide dipeptide, Propionibacterium parvum, BCG), were used. Most of the immunosuppressive drugs stimulated DTH while inhibiting GVHR. Most of the immunostimulating substances suppressed DTH and failed to affect GVHR. The results of tests were time dependent. Regional GVHR and DTH cannot be used as mutually interchangeable in immunomodulatory testing, and different results of these tests after exposure to a given agent can be expected. Possible mechanisms of action which would explain these differences are suggested in the discussion. PMID- 1597253 TI - Teratogenicity testing based on the interaction with a mutant allele. AB - The system of congenic strains of the laboratory rat carrying the mutant allele lx which is determining the polydactyly-luxate syndrome (PLS) was used for testing teratogenicity of six compounds from different pharmacological groups (cyclophosphamide, cyadox, carbadox, imipramine, verapamil, TIA). The interaction of the mutant lx allele with cyclophosphamide was highly significant (P less than 0.001) involving both polydactyly and tibial hemimely. Significant interaction with the lx allele was also proved after cyadox and carbadox treatment when compared with lx allele penetrance in LEW/BN, +/1x heterozygotes (P less than 0.01 and 0.05). In accord with our previous experiments, the teratogenic activity of the compounds tested seems to be connected with the ability to interact with nucleic acid structure and/or function. PMID- 1597254 TI - Effect of thymus cell-conditioned medium on recovery of haemopoiesis destroyed by gamma radiation. AB - The effect of thymus cell-conditioned medium (TCCM) on haemopoiesis recovery in spleen, bone marrow and thymus was studied in mice injured by a single dose of 5.8 Gy of ionizing radiation. TCCM given 18 h before irradiation accelerated haemopoiesis recovery in splenic red pulp, and in part in bone marrow. Reparation of splenic white pulp and thymus was not influenced by TCCM application. PMID- 1597255 TI - The germ layer origin of mouse vaginal epithelium restricts its responsiveness to mesenchymal inductors: uterine induction. AB - The epithelium of the mammalian vagina arises from two distinct germ layers, endoderm from the urogenital sinus and mesoderm from the lower fused Mullerian ducts. While previously it has been reported that neonatal vaginal epithelium can be induced to differentiate as uterus, which normally develops from the middle portion of the Mullerian ducts, it has not been determined whether this ability is shared by both mesoderm- and endoderm-derived vaginal epithelia. To test if germ layer origin influences the ability of vaginal epithelium to undergo uterine differentiation, we have isolated sinus-derived and Mullerian-derived vaginal epithelia from newborn mice, combined them with uterine mesenchyme, and grown them for 4 weeks in female mice. Mesoderm-derived Mullerian vaginal epithelium in combination with uterine mesenchyme formed the simple columnar epithelium typical of uterus. Similar results were obtained with neonatal cervical epithelium, another mesodermal Mullerian duct derivative. On the other hand, sinus vaginal epithelium combined with uterine mesenchyme formed small cysts lined by a stratified squamous vaginal-like epithelium. This epithelium never showed evidence of cycling between the cornified and mucified states as is typically seen in vaginal epithelium combined with vaginal stroma. These results indicate that the ability of epithelium to form uterus is limited to mesoderm-derived epithelia and suggest that endoderm-derived sinus vaginal epithelium cannot undergo the typical differentiative modifications in response to the hormonal fluctuations of the estrous cycle when associated with uterine stroma. PMID- 1597256 TI - The carboxy-terminal extension of the collagen binding domain of fibronectin mediates interaction with a 165 kDa membrane protein involved in odontoblast differentiation. AB - Terminal differentiation of the odontoblast is characterized by an elongation and a polarization of the cell. The change in the cell shape and the reorganization of the cytoplasm involve the microfilament system. An immunological approach has previously implicated a transmembrane interaction between fibronectin and vinculin in the control of odontoblast differentiation. A 165 kDa protein localized on the cell-surface of odontoblasts mediated this interaction. In order to define the nature of the interaction of the 165 kDa protein with fibronectin, peptides were prepared by proteolytic cleavage of fibronectin with alpha chymotrypsin. The results indicate that the 165 kDa protein interacted with a 62 kDa peptide located towards the amino-terminal extremity of fibronectin, but not with a 47 kDa related fragment. Both these 62 kDa and 47 kDa peptides included the collagen-binding domain and were retarded on a heparin-Ultrogel column. Microsequences demonstrated that the 62 kDa and 47 kDa fragments had the same amino-terminal extremity and that the larger fragment was extended in the carboxy terminal direction. This carboxy-terminal extension of the collagen binding domain of fibronectin is implicated in the interaction of this molecule with the 165 kDa protein. On the other hand, odontoblasts differentiated normally when tooth germs were cultured in the presence of GRGDS synthetic peptide, suggesting that RGD-dependent integrins were not involved in odontoblast differentiation. Staining of dental mesenchymal cells in primary culture and of differentiated odontoblasts in situ with antibodies directed against the beta 1-subunit of integrins confirmed previous observations and showed that although beta 1 integrins are involved in the attachment of cultured dental cells, they are not implicated in the process of odontoblast differentiation. PMID- 1597257 TI - Temporal relationships between induced changes in c-myc mRNA abundance, proliferation, and differentiation in HL60 cells. AB - Changes in the relative abundances of c-myc mRNA have been related to changes in other parameters of differentiation (histochemical, clonogenic) during the course of the differentiation of HL60 cells to monocytes/macrophages or to granulocytes. Induction of differentiation to monocytes/macrophages was marked by a rapid rate of appearance of committed cells (80 to 90% in 24 hours) and a concomitant rapid loss of c-myc mRNA. Induction of granulocytic differentiation resulted in a much slower rate of appearance of committed cells (50% in 48 hours), and a much faster rate of loss of c-myc mRNA (tenfold in 1 hour). These data are consistent with there being a direct link between down-regulation of the expression of c-myc and the onset of proliferation arrest and monocytic differentiation, but show there is no such association of c-myc mRNA abundance and proliferation or differentiation during the maturation of HL60 granulocytes. PMID- 1597258 TI - Recommendations for the conduct of acute inhalation limit tests. Prepared by The Technical Committee of the Inhalation Specialty Section, Society of Toxicology. AB - This paper reviews the scientific issues related to exposure concentrations and particle sizes used in acute inhalation limit tests. The current United States Environmental Protection Agency (USEPA) recommended exposure concentration for such tests is 5 mg/liter; while this level is very high, it is often achievable. On the other hand, its toxicological relevance is questionable. The USEPA recommendation that 25% of the particle distribution be less than 1 micron is a more difficult issue to address. Physical laws for aerosol particle generation and behavior limit the minimum size of particles in an exposure atmosphere at a concentration of 5 mg/liter. Particle size also influences deposition site in the respiratory tract. Since damage to any region of the respiratory tract can produce lethality, and it is not possible to predict, a priori, the most responsive region of the tract or the most harmful particle size of an untested agent, acute limit testing should employ particles in a size range that deposits throughout the entire rodent respiratory tract. Particles between 1 and 4 microns mass median aerodynamic diameter (MMAD) are well suited for such studies. It is, therefore, recommended that the limit test concentration should be the highest concentration (up to 5 mg/liter) that can be achieved while still maintaining a particle size distribution having an MMAD between 1 and 4 microns. PMID- 1597259 TI - Alterations in rat flash and pattern reversal evoked potentials after acute or repeated administration of carbon disulfide (CS2). AB - Because solvents may selectively alter portions of visual evoked potentials, we examined the effects of carbon disulfide (CS2) on flash (FEPs) and pattern reversal (PREPs) evoked potentials. Long-Evans rats were administered ip carbon disulfide either acutely or for 30 days. FEPs or PREPs were recorded prior to and 1, 2, 4, 8, or 24 hr after a single dose of CS2 (0, 100, 200, 400, or 500 mg/kg). Flash evoked potentials were also recorded 1, 2, 6, and 24 hr after the last of 30 doses of 200 mg CS2/kg/day. Acute exposure to CS2 consistently decreased the amplitude of FEP peak N160 at 1 hr, depressed peak N30 amplitude over 2-4 hr, and increased the latency of peaks P21, N30, P46, N56, and N160 for up to 4 hr after treatment. Carbon disulfide decreased the amplitude of PREP peaks P65, N83, P88, and N122 4 hr after treatment. Colonic temperature was depressed up to 8 hr after treatment. Administration of 200 mg CS2/kg/day decreased the amplitude of FEP peak N30 and increased the latencies of peaks P21, N30, P46, N56, and N160 up to 24 hr after the last dose. The differential effects of CS2 on portions of FEPs indicate that FEP peaks can be independently modulated. Changes in PREPs were temporally correlated with alterations in early FEP peaks, but FEP peak N160 was depressed at an earlier time point. Repeated CS2 exposure affected FEPs at lower doses and for a longer time than an acute exposure, similar to the reported greater severity of neurological disturbances following repeated CS2 exposures in humans. PMID- 1597260 TI - Comparison of subchronic neurotoxicity of 2-hydroxyethyl acrylate and acrylamide in rats. AB - The comparative neurotoxicity of subchronic exposure to 2-hydroxyethyl acrylate (HEA) and acrylamide (ACR) was evaluated using a functional observational battery (FOB) and neuropathology. Three dose levels of each compound (HEA: 3, 20, 60 mg/kg; ACR: 1, 4, 12 mg/kg) were administered intraperitoneally to male and female Long-Evans rats (n = 10/sex/dose level), 5 days/week for 13 weeks. Two vehicle control groups were also included. The FOB, which includes home-cage and open-field observations and interactive tests of sensory, neuromuscular, and autonomic function, was administered before dosing, at monthly intervals, and on the day after the last dose. Subsets of rats (n = 6/sex/dose level) were then perfused and tissues from the brain, spinal cord, and peripheral nerve were prepared for light microscopic evaluation. There were clear differences between the effects of HEA and ACR. ACR produced time- and dose-related changes in FOB measures of muscle tone and equilibrium, and produced axonal degeneration in peripheral nerves and within long tracts of the spinal cord. HEA exposure was also associated with changes in muscular function on FOB testing, but the magnitude of the effects was not as great as with ACR and not dose related. In addition, no neuropathological changes were detected after HEA exposure. Thus, the effects of HEA did not resemble those of ACR. The FOB data were summarized in domains of neurobehavioral functions. Using a composite score analysis, ACR was shown to produce prominent effects in the neuromuscular domain whereas HEA was largely without effect. When the data are analyzed in this manner, the neurotoxic potential of HEA appears to be minimal. PMID- 1597261 TI - Age-dependence of responses to acute ozone exposure in rats. AB - Previous work from this laboratory demonstrated that neonatal rats and postweanling rabbits are more sensitive to ozone-induced stimulation of pulmonary arachidonic acid (AA) metabolism than are young adults (Fundam. Appl. Toxicol. 15, 779.) In the study reported here, we have extended our initial investigation to include the influence of animal age on temporal aspects of pulmonary AA metabolism and several other responses to brief exposures to 1 ppm ozone. Rats of discrete ages ranging from 13 days to 16 weeks were exposed to 1 ppm ozone or to air for 2, 4, or 6 hr. Immediately following exposure the lungs were lavaged with six consecutive volumes of phosphate-buffered saline and the acellular fluid from the first lavage volume recovered was analyzed for its content of prostaglandin E2 (PGE2), protein, and lactate dehydrogenase. Leukocytes recovered by lavage were quantitated and characterized by viability and percentage of polymorphonuclear (PMN) cells. Several lines of evidence verified that PGE2 was produced by the lung as a consequence of ozone exposure and that its concentration in the fluid from the first lavage was a reasonably good index of pulmonary AA metabolism to prostanoids. We also demonstrated that the lavage process itself stimulates the lung, resulting in increased AA metabolism to prostanoids that were recovered in the second and following lavage volumes. The time course of PGE2 production by the ozone-exposed lung varied considerably with animal age. Neonatal rats 13 days of age were the most sensitive to ozone stimulation. At 2 hr of exposure, PGE2 concentration in the first lung lavage of these animals peaked at values approximately two orders of magnitude above controls and then decreased sharply with continued exposure. Adults and older neonates (18 days of age) were much less responsive to 2-hr exposures; however, continued exposure of these rats for up to 6 hr resulted in increasing PGE2 concentration in the first lung lavage. Other responses showed various degree of age dependence. The percentage of lavaged leukocytes that were nonviable (i.e., trypan blue-positive) showed a strong inverse correlation with animal age. In 13 day-old rats that were exposed for 6 hr, the percentage of dead leukocytes reached nearly 50%. In addition, sheets or clumps of dead cells that were judged to be epithelial cells were lavaged from these animals. Conversely, 16-week-old adult males exposed to ozone for 6 hr showed little evidence of damage to cells of the respiratory tract.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597262 TI - Hydroquinone: a developmental toxicity study in rats. AB - To determine the potential developmental toxicity of hydroquinone (HQ), pregnant rats (COBS-CD-BR) were given 0, 30, 100, or 300 mg/kg HQ by gavage on the 6th through the 15th days of gestation. Maternal effects included a slight, but significant (p less than or equal to 0.05), reduction in body weight gain and feed consumption for the 300 mg/kg HQ dams. Reproductive indices, i.e., pregnancy rate, numbers of corpora lutea, implantation sites, viable fetuses, and early and late resorptions, fetal sex ratio, pre- and postimplantation losses, and gravid uterine weights, were not affected by treatment with HQ. A slightly reduced (p less than or equal to 0.05) mean fetal body weight seen at the 300 mg/kg dose level was associated with the slightly reduced body weight gain seen for the dams at this dose level. Gross external, internal soft tissue, and skeletal examinations of the fetuses revealed no HQ-related malformations. The incidences of gross external variations (small hematomas) and internal soft tissue variations (dilated renal pelvis, hydronephrosis, and hydroureter) in the HQ treated litters were not statistically different from the control incidences. Skeletal variations (delayed ossification of membranous skull bones, hyoid bone, thoracic centra 1-3, sacral arches 3 and 4, and bilobed thoracic centra 9-13) were seen with similar frequency in the control and HQ-treated groups. A statistically significant increase in the incidence of total common vertebral variations seen at the 300 mg/kg HQ dose level was not considered toxicologically significant. The incidences of total skeletal variations were not statistically different between the control and the HQ-treated groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597263 TI - Effect of supplementation with folinic acid, vitamin B6, and vitamin B12 on valproic acid-induced teratogenesis in mice. AB - The effect of administration of folinic acid, vitamin B6 + vitamin B12, and their combination on valproic acid (VPA)-induced teratogenesis was studied in NMRI mice. VPA (500 mg/kg, sc) was injected on Day 8 of gestation and the vitamins (two dose levels) were injected ip 1 hr before, immediately before, and 1 hr after VPA administration. Folinic acid significantly reduced VPA-induced resorptions (21-24%), and palate, rib, and sternebral malformations. Exencephaly and spina bifida occulta were also reduced (14 and 40%, respectively), but the difference was not statistically significant. On the other hand, vitamin B6 + vitamin B12 significantly reduced VPA-induced exencephaly (23%), spina bifida occulta (80%), palate and rib malformations, kidney abnormalities, and fetal weight retardation. A combination of the three vitamins was effective in reducing VPA-induced exencephaly (23-30%), spina bifida occulta (60%), and palate and rib malformations. The protection against VPA-induced malformations was not complete and was not always dose related, and the reduction in exencephaly rate was only significant in the absence of a reduction in resorption rate. Full-length cleft palate, sternebral malformations, and retarded sternebral and caudal ossification were, however, increased by the high dose of combined vitamin administration. The present study supports the view that VPA-induced teratogenesis may be mediated via an interaction with folate metabolism. Although folinic acid and vitamin B6 + vitamin B12 can effectively reduce VPA malformations, the protection was not complete, which may suggest the involvement of other factors. Furthermore, the dose levels should be carefully chosen since high doses of the combined vitamins can actually increase the incidence of certain defects. PMID- 1597264 TI - Arthritis and hematological changes induced by an analogue of muramyl dipeptide in rats. AB - We examined changes of blood cell counts and development of arthritis induced by daily subcutaneous injections of MDP-Lys(L18), an analogue of muramyl dipeptide (MDP), in rats. The numbers of neutrophils markedly increased in the peripheral blood 4 hr after the 1st, 7th, and 14th administrations of MDP-Lys(L18), but they recovered to the control levels within 24 hr. Monocyte and lymphocyte counts increased after the 7th and 14th administrations, respectively, although both decreased after the 1st dosing. Serum inflammatory markers, such as albumin, globulin, mucoprotein, sialic acid, and iron, showed marked changes after the 1st administration. Histopathologically, the synovial membrane of the tarsal joint showed a multilayer arrangement of synoviocytes with vesicular cytoplasms and infiltration of neutrophils from 6 hr after the 1st administration of the drug. The acute synovitis was gradually enhanced until 24 hr later. The synovitis was greatly decreased in degree after the 3rd administration, but increased again later. After the 7th and 14th administrations, mononuclear cells and lymphocytes, respectively, infiltrated the synovial membrane, in a manner corresponding to the hematological findings. However, exudative changes and neutrophilic infiltration were still observed after the 14th drug administration, and the synovitis was repaired after a 7-day recovery period. PMID- 1597265 TI - Comparative carcinogenicity of ethylene thiourea with or without perinatal exposure in rats and mice. AB - Chronic toxicity and carcinogenicity studies of ethylene thiourea (ETU), 97% pure, were conducted in F344/N rats and B6C3F1 mice of each sex. The major objective of the study was to determine if incorporation of perinatal exposure, in addition to the conventional exposure of young adult animals for 2 years, enhances the sensitivity of the bioassay in identification of the carcinogenic potential of chemicals when compared to the conventional exposure of animals to a chemical for 2 years, usually beginning at the age of 6-8 weeks. The studies were designed to determine (1) the toxic and carcinogenic effects of dietary ETU in rats and mice receiving perinatal exposure up to 8 weeks of age followed by control diet for 2 years, (2) the effects of ETU in rats and mice receiving exposure for 2 years beginning at the age of 8 weeks, and (3) the effects of combined perinatal/adult exposure to ETU (perinatal exposure to 8 weeks of age followed by the adult exposure for 2 years). During the perinatal period, rats were exposed to dietary ETU concentrations ranging from 9 to 90 ppm and adult exposure concentrations ranged from 25 to 250 ppm. In the mice, the perinatal exposure concentrations of ETU in the diet ranged from 33 to 330 ppm, and in the adults the concentrations were 100 to 1000 ppm. A total of eight exposure groups (including controls) were used with 60 animals in each group. Ten animals from each group were killed at Month 9 of the study for interim evaluation. The thyroid gland in rats and mice and the liver in mice were identified as target organs of ETU toxicity at the 9-month interim evaluation. The perinatal only exposure to ETU was not carcinogenic in rats or mice, while adult or perinatal/adult combination exposures to ETU were carcinogenic both in rats and in mice. The thyroid gland was the major site of ETU carcinogenicity both in rats and in mice. The liver and pituitary glands were other major sites of ETU carcinogenicity in mice. The carcinogenic effects of ETU were generally similar by adult and perinatal/adult combination protocols except that the incidences of thyroid tumors were slightly higher in the rats receiving the perinatal/adult combination of ETU exposure in the diet. PMID- 1597266 TI - Evaluation of the inhalation toxicity of diethylethanolamine (DEEA) in rats. AB - Diethylethanolamine (DEEA), an industrial anticorrosive additive, was evaluated in rats for its potential toxicity. A 2-week inhalation exposure to 10 ppm revealed no signs of toxicity. At 56 ppm, rats exhibited signs of nasal irritation and corneal opacities. Significant mortality (males, 90%; females, 50%) occurred at 301 ppm. Histopathology revealed inflammatory cell infiltrations of the nasal turbinate mucosa and squamous metaplasia after exposure to 56 ppm. In the 14-week subchronic study, rats were exposed to 0, 11, 25, or 76 ppm. During exposure to DEEA, transient signs of mild to moderate respiratory irritation (noises or rales) were observed with a frequency and severity that was dose dependent. These signs usually cleared within 1 hr post-exposure. However, at 76 ppm some rats continued to exhibit these respiratory signs overnight. There were no significant DEEA-induced changes in either blood chemistry or neurobehavioral parameters. Nasal cavities of rats exposed to 25 or 76 ppm revealed evidence of inflammatory cell infiltration, focal hyperplasia, and squamous metaplasia in the respiratory epithelium of the anterior nasal turbinates. Hypertrophic goblet cells, focal necrosis, and exudate in the nasal lumen were also seen at 76 ppm. DEEA vapors failed to produce persistent ocular or respiratory tract toxicity below 26 ppm. The no-observed-effect-level in this study was 10 ppm. PMID- 1597267 TI - Acute urinary tract toxicity of tetraethylorthosilicate in rats. AB - Acute stomach, kidney, and bladder toxicity was evaluated in F344 rats after gastric gavage of tetraethylorthosilicate (TES) at daily doses of 0, 0.111, 0.223, and 0.333 g. Five rats of each sex at each dose were sacrificed after 1, 2, and 4 days. In TES-treated groups, silicate accumulated in the stomach glands and the muscle layer of the forestomach and glandular stomach. Serum chemistries demonstrated acute onset of renal failure. In the kidneys, acute tubular necrosis, accumulation of silicates, and superficial necrotizing papillitis were observed. In the renal pelvis and bladder, there was urothelial simple hyperplasia, focal erosion of the mucosa, edema, and inflammation. These acute toxic changes were dose and time dependent, but significant sex differences were not observed. The microscopic changes in the urothelium were similar to those observed following administration of high doses of sodium saccharin to male rats in which urinary silicate precipitate and crystals form. PMID- 1597268 TI - Bovine corneal opacity and permeability test: an in vitro assay of ocular irritancy. AB - Most of the published in vitro tests of ocular irritancy investigate a single parameter, generally cytotoxicity, using different cell types in culture. Although good correlations with in vivo data have been reported by some investigators, many of these studies examined only limited classes of products, mainly surfactants and cosmetic ingredients. To predict the irritant potential of compounds in development and process intermediates (which include a wide variety of chemical classes with variable physical characteristics), an assay which would allow great flexibility was needed. A recently published model of corneal opacity was appropriate for this purpose and therefore investigated. The method was substantially modified and extended to study, in the same assay, two important components of irritation, i.e., opacity and permeability. For opacity alone, values obtained for 44 common chemicals showed a correlation of r = 0.73 with published in vivo data. However, compounds like sodium lauryl sulfate and some medium-chain alcohols gave false-negative results, apparently because they produced destruction of corneal epithelium. Such an effect was quantified by the measure of corneal permeability to fluorescein, and changes observed were found to be consistent with the known irritant potential of the compounds. In combination, the measurement of these two endpoints thus appeared to be sufficient to accurately predict ocular irritancy. This was further verified with 15 process intermediates. In short, the bovine corneal opacity and permeability assay allows investigation of two important components of eye irritation, in a one-day experiment, using an ocular tissue. It represents a useful approach to assess ocular irritation at least for our needs. PMID- 1597269 TI - Integration of the human lymphocyte into immunotoxicological investigations. AB - The xenobiotics acetoxydimethylnitrosamine (ACDMN), acrolein (ACR), and 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) are potent immunosuppressive agents of the in vitro primary humoral response of murine splenocytes. The focus of these studies was to determine if human lymphocytes could be modulated by direct exposure to these xenobiotics and therefore be used as an in vitro model system for immunotoxicological investigations. In these studies, we compared the profile of activity of these xenobiotics on cultured murine splenocytes (SPLC) and human tonsillar lymphocytes (HTL). With SPLC, we measured the anti-sheep erythrocyte (SRBC) IgM response with the standard direct plaque assay, pokeweed mitogen (PWM) induced proliferation and the total IgM response to PWM with the reverse plaque assay (RPA). With HTL, we measured PWM-induced proliferation and the total Ig(M+A+G) response to PWM with the RPA. ACDMN inhibited the murine SPLC anti-SRBC antibody response, PWM-induced proliferation and IgM antibody-forming cell (AFC) responses at concentrations between 0.1 and 10 microM. In HTL, ACDMN inhibited PWM-induced proliferation and the Ig(M+A+G) AFC response over a comparable concentration range. ACR had little activity at concentrations of 10 microM or less. However, ACR at a concentration of 100 microM completely suppressed all the responses of either SPLC or HTL. This concentration was also associated with a marked decrease in cell viability. In contrast, TCDD had a different profile of activity. TCDD inhibited the murine SPLC anti-SRBC IgM response at 3.0 and 30 nM. However, TCDD had no effect on either PWM-induced proliferation or antibody production in either murine SPLC or HTL. TCDD did cause a significant reduction in the background proliferation (i.e., no PWM) of both murine SPLC and HTL at all doses tested. These studies suggest that HTL can provide a comparable profile of activity as murine SPLC and can therefore be utilized for evaluating the direct immunotoxic potential of certain xenobiotics. PMID- 1597270 TI - Preclinical safety evaluation of dilevalol (SCH 19927), an antihypertensive agent, in the rat. AB - Dilevalol (SCH 19927) is an antihypertensive agent with direct vasodilating properties due to beta 2-adrenergic receptor agonist activity and nonselective beta-receptor blocking activity. In acute (single dose) oral and parenteral studies a low order of toxicity was observed. Clinical signs observed at the higher doses included salivation, prostration, tremors, and convulsions. In multidose oral studies dilevalol produced an increase in mean absolute and/or relative heart weights observed as early as 1 month in the high-dose (300 mg/kg) rats and at all dose levels (35, 90, 220 mg/kg) in rats treated for 1 year. There were no microscopic changes that could be associated with the change in heart weight. Intraalveolar macrophages were observed in the lung tissue of rats treated for 3 months or 1 year with an increase in relative lung weights noted in the high-dose (220 mg/kg) group treated for 1 year. In a 2-year rat study, no evidence of oncogenicity was observed. On the basis of these studies, dilevalol has a low order of toxicity and lacks oncogenic potential in the rat. PMID- 1597271 TI - [CIN and pregnancy, a 20-year retrospect]. AB - This is a report on CIN associated with pregnancy in a review over the last 20 years. Biological tumour behaviour, diagnostic problems and therapy are discussed in 100 cases of preinvasive and invasive lesions of the cervix. It is pointed out that low acceptance of early detection measures in association with late pregnancy planning may contribute to an increase of invasive cancer in pregnancy. PMID- 1597273 TI - [Vaginal ultrasound studies of cervix closure with special reference to parity]. AB - In this study, the cervical length, thickness, the width of the internal os, the cervical canal and the external os of 62 primipara and 77 multipara were measured vaginosonographically. Only patients with normal pelvic scores were examined. The measurements were carried out approx. every fortnight between the 16th and 34th gestational week. In the primipara group, the average cervical length was 36.8 mm +/- 12.0 mm, the thickness 27.8 mm +/- 4.4, the width of the internal os 6.3 +/- 2.1 mm, the cervical canal 4.2 +/- 2.0 mm and the external os 5.4 +/- 2.2 mm. In the multipara group, an average cervical length of 40.1 mm +/- 7.4 mm, a thickness of 29.3 +/- 3.9 mm, an internal os of 5.1 +/- 2.6 mm, a cervical canal of 4.3 +/- 1.3 mm and an external os of 5.8 +/- 1.8 mm were found. Contrary to our expectations, there was no statistically significant difference between the two groups. Furthermore we did not find any correlation between the internal and the external os. PMID- 1597272 TI - [Heroin abuse and methadone substitution in pregnancy]. AB - The pre- and postnatal data of 20 pregnant heroin addicts and their neonates are described. 16 women were treated with methadone to prevent withdrawal symptoms. A relatively stabile prenatal condition with a decrease of complications was achieved. On the other hand, the neonates suffered from severe withdrawal symptoms including seizures in spite of intensive paediatric care and prophylactic treatment with barbiturates. After a mean follow-up of one to two years a relatively good neurological development of the children was observed. PMID- 1597274 TI - [Spontaneous rupture of the liver in HELLP syndrome]. AB - Spontaneous hepatic rupture in pregnancy is a rare, but dangerous complication of acute or progressing pre-eclampsia. Pain in the right upper quadrant is the most important clinical symptom and should prompt immediate laboratory evaluation (transaminase, coagulation profile, platelet count, red and white blood count). If the diagnosis of HELLP syndrome is confirmed, close supervision in an intensive care unit is mandatory. The danger of pre- or postpartal open hepatic rupture must be considered. Pain in the right upper abdomen and signs of abdominal mass bleeding occurring within a HELLP syndrome are important evidence for hepatic rupture. Immediate ultrasonic examination may verify the tentative diagnosis. The usual therapy is then laparotomy with attempted surgical haemorrhage control. A conservative clinical haemorrhage control attempt is possible in exceptional cases only. Patients developing a HELLP syndrome although otherwise in seemingly perfect health, require closely meshed monitoring to exclude hepatic rupture. PMID- 1597275 TI - [Prognostic factors of radically operated stage Ib cervix cancer]. AB - The present retrospective study attempts to evaluate the significance of factors such as age, histological type, histological grading, tumour size, lymph node metastases and tumour infiltration of the corpus uteri. Between 1975 and 1988, 312 patients were operated at our department or referred to postoperative radiotherapy. They fulfilled the inclusion criteria: histopathological stage Ib and radical hysterectomy with pelvic lymphadenectomy. The multivariate analysis confirmed, that the factors histological grading (G3 vs G1 + G2: relative risk (RR) = 2.66; 95% confidence interval (CI) = 1.36-5.18), tumour size (tumour infiltration of the cervix greater than 2/3 vs less than 2/3: RR = 2.36; 95% CI = 1.07-5.17), and pelvic lymph node metastases (positive vs negative: RR = 5.36; 95% CI = 2.70-10.65) are of significant importance for the survival. The results show, that patients with a cervical carcinoma in FIGO stage IB, with an infiltration of more than two thirds of the cervix with a more or less differentiation and with or without positive lymph node status, should be classified as high risk patients. In these unfavourable situations, a prospective randomised study should clarify the success rate of adjuvant therapy. PMID- 1597276 TI - [The value of intraoperative rapid biopsy study in diagnosis of breast cancer]. AB - 432 biopsies of mammary tumours performed between 1988 and 1990 were reviewed to evaluate the accuracy of rapid frozen section diagnosis. 15 (3.47%) had to be deferred to await subsequent permanent paraffin section. There were 4 (2.55%) false negative diagnoses. These cases consisted of small, nonpalpable and in-situ lesions. No false positive diagnosis was noted during the observation period. Sensitivity of frozen section histology was 97.45%, specificity 100% and efficiency 96.53%. Rapid frozen section diagnosis is a highly accurate and reliable tool which helps to avoid a consecutive operation in patients with breast cancer. PMID- 1597277 TI - [The value of the urethral depression quotient in diagnosis of female stress incontinence using the Brown-Wickham method]. AB - Various parameters of the urethral pressure profile have been developed to improve diagnosis of genuine stress incontinence. By application of micro-tip transducers, a positive correlation between "depression ratio" and degree of incontinence as had been observed by Eberhard. The aim of this study was to examine Eberhard's observations by the use of Brown-Wickham's method. Significant differences in the parameters of the urethral pressure profile during stress, such as the urethral closure pressure, depression pressure, depression ratio, transmission ratio, and the area of continence, were found between continent and incontinent patients. Although pressure transmission and transmission ratio revealed significant differences, depression pressure and depression ratio were found to be similar in patients with mild and severe degree of incontinence. According to the results of this study, depression ratio does not reflect the degree of urinary loss, when open catheters are used. PMID- 1597278 TI - [Disseminated lymphangioleiomyomatosis]. AB - Clinical and histological findings of generalised lymphangioleiomyomatosis are demonstrated. A 40-year old woman died within a few weeks because of massive pulmonary involvement. Tumour mass in the area of the left ovary together with enlarged lymph nodes suggested a metastasising ovarian cancer. PMID- 1597279 TI - [Legal topics in gynecology and obstetrics. A legal case]. PMID- 1597280 TI - [Diagnosis of early extrauterine pregnancy by hCG determination in serum and Douglas puncture fluid]. PMID- 1597281 TI - Multiple defects in the retinal nerve fiber layer in glaucoma. AB - We investigated the parameters that correlated with multiple defects in the retinal nerve fiber layer in 77 human eyes with normal-tension glaucoma, 110 with chronic high-tension glaucoma, and 102 control eyes. All 187 glaucomatous eyes had a nerve defect that was multiple in 20 cases. Correlation was significant between the multiple defect and the type of defect in the nerve fiber layer (P less than 0.002), size of the disc (P less than 0.02), and oblique insertion of the disc (P less than 0.02), as evaluated by the chi-square test. By multivariate analysis, refractive error was a high-ranking risk factor for multiple defect. Eyes with multiple defects tended to have moderate myopia, a focal nerve fiber layer defect and a small optic disc (category scores 0.0932, 0.0878 and 0.0697) and were less likely to have a diffuse defect in the nerve fiber layer, emmetropia or hyperopia, and a normal disc size (category scores -0.1077, 0.0705, and -0.548). The multiple defect in the retinal nerve fiber in glaucoma was frequently focal and correlated with myopia and a small optic disc. PMID- 1597282 TI - Krause's end-bulb microtumor of the conjunctiva: optic and ultrastructural description of a case. AB - Ultrastructural examination of a conjunctival biopsy of a 90-year-old woman with a history of chronic lymphatic leukemia showed numerous densely packed structures located below the epithelial conjunctival layer. They were composed of concentrical flattened lamellae arranged around one or several clear cores containing a large number of mitochondria. The plasma membranes of the lamellae displayed large numbers of pinocytotic vesicles and resembled perineurial cell processes. The central areas were thought to be axons. Because of their conjunctional location and morphological features. The structures were categorized as nerve endings of the Krause's end-bulb type. The aberrant and profuse growth of these structures led to the diagnosis of Krause's end-bulb microtumor of the conjunctiva. We compare our findings with mucosal neuromas, paraneoplastic lesions and age-related alterations are discussed, although they differ morphologically from Krause's end-bulb microtumor. PMID- 1597283 TI - Electrocardiographic changes in institutionalized geriatric glaucoma patients. AB - A geriatric study was conducted on 213 institutionalized geriatric glaucoma patients (mean age 83.9 years) and 100 control patients (mean age 81.3 years). A 12-lead electrocardiogram (ECG) analyzed according to the Minnesota code was recorded for 212 glaucoma patients and 95 control patients. The most frequent finding (in 56% of the glaucoma patients and in 38% of the control patients, P less than 0.05) was a negative or isoelectric T-wave, suggestive of ischemic heart disease. ECG findings suggestive of coronary heart disease (Q/QS patterns, ST-segment depression, negative or isoelectric T-wave, third or second degree AV block, left bundle branch block or right bundle branch block, intraventricular block or atrial fibrillation or flutter) was seen significantly more often in glaucoma patients (164/212; 77%) than in the control patients (59/95; 62%). Seventeen percent of the glaucoma patients had atrial fibrillation (AF), which was significantly more than for the control group (8/95; 8%). There was no difference in the number of ECG changes between patients with bilateral open angle glaucoma and bilateral angle-closure glaucoma. The mean intraocular pressure of patients having AF (15.9 +/- 8 mmHg) was significantly lower than that of the other patients (18.4 +/- 11 mmHg) (P less than 0.05). Fifty-five glaucoma patients were considered blind (visual acuity less than 0.05 in the better eye). The visual acuity of patients having AF was lower than that of the other patients, and severe visual field defects (arcuate scotoma or a residual field in the temporal periphery) occurred, slightly more frequently in patients with AF (in 70% vs 51% of the other patients). Arrhythmias, especially AF, are connected with impairment of visual acuity and visual field defects in glaucoma patients. The result of this retrospective study indicate that ECG changes occur frequently, suggesting coronary heart disease in elderly glaucoma patients. PMID- 1597284 TI - The treatment of bullous rhegmatogenous retinal detachment. AB - We describe the results of a consecutive series of 97 cases of bullous superior retinal detachment treated by conventional surgery. The retinal detachments were characterized by either a single retinal break or multiple retinal breaks confined within 1 clock hour and no proliferative vitreoretinopathy. The surgery involved sequential drainage of subretinal fluid, injection of air, cryotherapy and the application of local explant. All cases would otherwise be suitable for pneumatic retinopexy. The anatomical success rate was 85.5% with a single operation and 97% with further procedures. We report on the complications encountered and appraise the advantages and disadvantages of this operation. Forty-five of the 97 cases had detachment of the macula for less than 2 weeks, and 35 of the 45 (80%) achieved a visual acuity of 6/18 or better. These visual results challenge the assertion that better visual outcome might be attained with pneumatic retinopexy. PMID- 1597285 TI - Retinal vessel measurement: comparison between observer and computer driven methods. AB - A method of semi-automated image analysis for the measurement of retinal vessel diameters is described. This was compared with an observer-driven method for reproducibility and accuracy. The coefficient of variation for the data from the semi-automated method was 1.5-7.5% (depending on the vessel diameter) compared to 6-34% with the observer-driven method. The mean vessel diameters using the observer-driven method tended to be higher; however, this did not reach significance. The speed and low inter- and intra-observer variability for the semi-automated method make it a useful technique for measuring retinal blood vessel diameters. A larger variability was found between photographs taken at different times. This may be due to changes in retinal vessel diameter with changes in retinal perfusion pressure during the cardiac cycle. PMID- 1597287 TI - Juvenile atrophy of pigment epithelium and choriocapillaris. AB - Two brothers, 20 and 21 years of age, are reported who had a circumscribed area of atrophy of the pigment epithelium, choriocapillaris and part of the choroidal vessels in the posterior pole; they were otherwise in good health. In addition, the optic discs, particularly in the older brother had hypoplastic characteristics. Both patients were known to have had low visual acuity and nystagmus since early childhood. Electro-oculography was normal. Electroretinography and color vision tests were subnormal in both patients. Although the morphological picture showed features similar to central areolar choroidal dystrophy, familial bilateral macular colobomata, serpiginous choroiditis and some cases of cone dystrophy, there are clinical and electrophysiological reasons for differentiating the cases presented here from these other diseases. PMID- 1597286 TI - Hemi-naevus of Ota: perturbation of neural crest differentiation as a likely mechanism. AB - We present a case of oculodermal melanosis that involves the lower eyelid and lower half of the globe in a very clearly defined fashion. We suggest that such a lesion is the result of a local change in embryonic environment occurring during a well-defined stage of ocular development, such that differentiation of neural crest cells into a melanocytic phenotype is favoured. PMID- 1597288 TI - Protracted ruthenium treatment of recurrent pterygium. AB - By combining excision with 106ruthenium irradiation in 17 patients previously operated on for persistently recurrent pterygium, we have devised an effective therapy that produces virtually no side effects and further prevents events recurrence. The ruthenium applicator shell was left in place for 2-3 h, yielding a total dosage of 2000 cGy. Only 2 of 17 patients suffered even slight recurrences, and 2 more had either motility disturbance or corneal haze. Through application of the internationally accepted total dosage of 2000 cGy, but at a relatively low dose rate, which especially protects the tissue responsible for proper healing, strong support is provided for the principle of protracted irradiation in recurrent (and possibly even primary) pterygium, permitting milder treatment and fewer recurrences. PMID- 1597289 TI - Anteroposterior shift in rigid and soft implants supported by the intraocular capsular bag. AB - We compared the depth of the anterior chamber and the optimal distance refraction in a group of patients with soft and rigid intraocular implants under pilocarpine (maximal ciliary contraction) and cyclopentolate (maximal ciliary relaxation) in order to determine if lens movement might account for the apparent accommodation phenomenon. Lens shifts ranging from 1.5 to 0.02 mm and refractive variations up to 1 D were found. However, the discrepancies between amount of shift and refractive variations suggest that lens movement does not play a relevant role in this phenomenon. PMID- 1597291 TI - Problems related to diffuse versus localized loss in the perimetry of glaucomatous visual fields. AB - The separation of diffuse loss from more localized loss in the glaucomatous visual field is desirable for a number of reasons. In previous papers, the characteristics of several methods and algorithms for distinguishing among normal visual fields and those exhibiting diffuse and localized loss have been described and compared. In particular, a new diffuse loss index has been introduced that serves to decide whether or not a diffuse loss component is present and, if so, helps to estimate the amount. Here the approaches utilized for calculating empiric probability maps (Heijl) and the pattern deviation plots (STATPAC) are compared with results obtained with the diffuse loss index algorithm. Based on 197 Octopus G1 examinations of glaucomatous visual fields, it is shown that both methods produce large differences when compared with the diffuse loss index. For this and other reasons, it is argued that both empiric probability maps and pattern deviation plots may lead the inexperienced clinician to ignore valuable information concerning actual pathology. PMID- 1597290 TI - Galactitol is not a cause of senile cataract. AB - It has been postulated that the accumulation of sugar alcohol, galactitol, from milk induces cataract in the eye lens through an osmotic mechanism. In this study the concentrations of galactitol and other sugar alcohols (sorbitol, mannitol and inositol) were measured by sensitive gas chromatography in the lenses of 15 patients operated on for senile idiopathic cataracts and in 14 clear lenses removed at autopsy. Large amounts of inositol (mean +/- SD, 4.1 +/- 3.1 vs 4.7 +/ 3.0 mumol/g lens wet weight) and small amounts of mannitol and sorbitol were detected in both study groups. Galactitol levels remained clearly below the detection limit (2 nmol/g) in all lenses. It seems unlikely that senile cataract is a result of the accumulation of galactitol in the eye lens. PMID- 1597292 TI - Precapsular layer of the anterior lens capsule in early pseudoexfoliation syndrome. AB - We examined a possible correlation between clinical signs of early pseudoexfoliation (PSX) syndrome related to pigment dispersion and iris stroma atrophy and morphological alterations of the lens capsule. 63 anterior lens capsules (30 PSX suspects, 3 pre-PSX, 10 PSX, 20 controls) were studied by transmission and immuno-electron microscopy (TEM). In 20 PSX suspect and 3 pre PSX capsulotomy specimens, TEM revealed a precapsular layer (0.1-11 microns in thickness) composed of microfibrils, amorphous material, and granular inclusions. The incidence of this fibrillar layer was significantly higher (p = 0.001) in PSX suspect and pre-PSX eyes than in controls (5 positive). Ultrastructural and immunohistochemical similarities of the fibrillar surface network in PSX suspect and typical PSX specimens indicate that the precapsular layer may represent a precursor of PSX. The beginning PSX process in the eye is obviously indicated by certain clinical signs. PMID- 1597293 TI - The source of sensory fibres of the inferior conjunctiva of monkeys. AB - Dissection, light and electron microscopy combined with degeneration induced by intracranial nerve lesions and superficial nerve transection were used to trace the sources of sensory fibres of the inferior conjunctiva of cynomolgus monkeys. Most nerves destined for the inferior conjunctiva were branches of the lacrimal nerve and entered the inferior eyelid laterally. Following unilateral ophthalmic neurotomy in three monkeys and combined ophthalmic/maxillary neurotomy in one monkey, substantial and regular degenerative changes were observed in the nerves and nerve-fibre bundles of the inferior conjunctiva. Following intracranial lesions of the maxillary nerve and of the infra-orbital nerve at its facial hiatus, conjunctival nerves showing induced changes were infrequent (four animals) or absent animal). The results indicate that the inferior conjunctiva is innervated mainly by the ophthalmic nerve contrary to the popular notion that it is innervated mainly or wholly by the infra-orbital branch of the maxillary nerve. PMID- 1597294 TI - A comparative immunohistochemical study of human corneotrabecular tissue. AB - Using in situ immunohistochemical techniques and a broad panel of antibodies directed against intermediate filament proteins, vascular endothelial markers, neuroectodermal/neuroendocrine markers, and monoclonal antibodies raised against human corneal endothelial cells (HCECs), a comparative phenotypical analysis was performed on HCECs, keratocytes, trabecular cells, and cells lining the canal of Schlemm. The coexpression of cytokeratins and neurofilaments by HCECs argues in favor of a neuroectodermal origin, which is further supported by the fact that they stain positive for neuron-specific enolase (NSE) and that they express neural cell adhesion molecules (N-CAM) at their surface. The expression of NSE and N-CAM also applies to the trabecular cells. The cells lining the canal of Schlemm were found to share many immunophenotypical features with vascular endothelial cells (i.e., factor-VIII-related antigen and BMA-120), rather than with HCECs. This was further supported by the reactivity of two monoclonal antibodies (i.e., 9.3 E and 5.52 H) that were raised against HCECs, and which labelled vascular endothelium and cells lining Schlemm's canal. PMID- 1597295 TI - Vascular occlusion of the retina: an experimental model. I. Leukocyte aggregates. AB - A new technique was developed to study the pathogenesis of retinal arteriolar occlusion in the pig. Using a catheter with its tip in front of the exit of the ophthalmic artery, autologous microparticles could be injected directly into the retinal arterial system. These microparticles were C5a-des-Arg stimulated leukocytes, which were aggregated to pellets of different sizes ranging from 0.26 to 1.0 mm. For better adhesion of the aggregates to the endothelium, endothelial damage was induced by the injection of additional substances, including methomidate and endothelial antibodies. In a further series of experiments systemic hypoxemic conditions were created over several hours prior to injection of the leukocyte aggregates. This resulted in cotton-wool spots and arterial branch occlusions with retinal edema. Furthermore, retinal hemorrhages occurred. This experimental model seems to be appropriate for mimicking retinal arteriolar occlusion syndromes. PMID- 1597296 TI - Vascular occlusion of the retina--an experimental model. II. Platelet aggregates. AB - Using a new technique to mimic arteriolar occlusion syndromes, different microparticles were injected into the ophthalmic artery of pigs. These microparticles were platelet aggregates of various sizes ranging from 0.15 mm to more than 0.8 mm. Aggregation was induced using adenosine diphosphate and thrombin. In some experiments, acetylsalicylic acid and histamine were also applied. In a further series of experiments, mixed aggregates containing platelets and leukocytes were injected. The results were observed by indirect ophthalmoscopy and consisted of superficial and deep retinal infarction. Large platelet aggregates resulted in arterial branch occlusion, whereas mixed and small platelet aggregates produced occlusion of small arterioles. This technique seems to be valuable in studying retinal arteriolar occlusion syndromes. PMID- 1597298 TI - Retinal pigment epithelium implantation in the rabbit: technique and morphology. AB - Dysfunction of the retinal pigment epithelium (RPE) is a major component of many degenerative disorders of the retina. We have developed a modified pars plana technique for subretinal implantation of homologous, cultured, carbon-loaded RPE cells in the rabbit. The natural history and morphologic behavior of the implanted RPE cells for up to 6 weeks after transplantation were observed in successful procedures. PMID- 1597297 TI - Pathogenesis of Purtscher's retinopathy. An experimental study. AB - Laboratory and clinical observations have implicated microparticles in the pathogenesis of Purtscher's retinopathy, which leads to the occlusion of small arterioles. These microparticles may be caused by aggregated leukocyte platelets or fibrin clots. The phenomenon of intravascular coagulation is well known following trauma or acute pancreatitis. Purtscher's retinopathy is linked with both diseases. To support this presumed pathogenesis of Purtscher's retinopathy, fibrin clots ranging in size from 0.15 to 1.0 mm were injected into the ophthalmic artery of the pig. They resulted in superficial and deep retinal infarctions. In addition, flame-shaped and spotted hemorrhages occurred. These retinal changes are characteristic of Purtscher's retinopathy. PMID- 1597299 TI - [Continuous Fick cardiac output measurement during inhalation anesthesia]. AB - A computer based system that continuously monitors cardiac output (CO) and the other hemodynamic variables has been developed. Fick CO was calculated every 10 sec on breath by breath basis. The arterio-venous oxygen content difference was measured by a combination of a pulse oximeter and a fiberoptic oximeter. Oxygen consumption was calculated by a direct measurement of respiratory gas exchange: airway flow was obtained from a Servo 900C ventilator and the instantaneous oxygen concentration was measured with a paramagnetic oxygen sensor. This system enabled us to use inhalation anesthetics which were avoided during Fick CO measurement with a zirconium oxygen sensor. Fick CO was compared to electromagnetic CO (EMCO) in 5 dogs anesthetized with enflurane. A total of 198 simultaneous data of CO measurements had a range from 0.5 to 2 l/min. Simultaneous measurements of Fick CO and EMCO showed a good correlation (r = 0.97), and a regression equation was: Y = X + 0.029. Fick CO was compared with cardiac output measured by a conventional thermodilution method (TDCO) in 12 patients anesthetized with either enflurane or isoflurane. A total of 207 simultaneous CO measurements ranged from 3 to 10.2 l/min. Regression analysis of 207 paired Fick CO and TDCO values showed a good correlation (r = 0.94), and a regression equation (Fick CO = TDCO-0.28). The "limits of agreement" (mean difference +/- 2 SD of bias) were within +/- 1.12 l/min, which could be acceptable for clinical settings. When hemodynamic states were abruptly changed by an intravenous administration of isoproterenol, Fick CO reached 90% of EMCO change within 30 sec. The author concludes that this system provides virtually continuous hemodynamic analyses and facilitates more sophisticated circulatory control of the patients within a limited fluctuation. PMID- 1597300 TI - [Clinicopathological study of Joseph disease: report of 4 pedigrees and its nosological consideration]. AB - Four pedigrees of Machado-Joseph disease (MJD) were reported. Main clinical features of 21 patients in these pedigrees were cerebellar ataxia, limb spasticity, gaze nystagmus, facio-lingual twitchings, and external ophthalmoparesis. Amyotrophy, hypokinesia, or dystonia were manifested with advance of the illness. In patients with younger onset age, such extrapyramidal signs were dominated. Neuropathological study of one autopsied case disclosed that there were degeneration of spinocerebellar tract, anterior horn cells, pontine nuclei, dentate nucleus, red nucleus, substantia nigra, internal segment of globus pallidus, subthalamic nucleus, and motor nuclei of brain stem; neurons of cerebellar cortex and inferior olivary nucleus were preserved. From these clinical and pathological features, these 4 pedigrees satisfied the criteria of MJD, and were differentiated from hereditary olivopontocerebellar atrophy. Currently, MJD is accepted as a new entity of hereditary spinocerebellar ataxias. However, there are still controversies as to whether Azores-Portuguese MJD and Japanese MJD are identical disorder. Furthermore, the nosological relationship between MJD and a number of similar cases, as reported historically under the diagnosis of Brown type ataxia or Marie's ataxia, has not been clearly established. From reviewing such cases critically, pathological and clinical features of our cases are so similar to those of the latter, indicating that the probably identical genetic disorder has been classified under the different categories. PMID- 1597301 TI - [Studies on flow cytometric analysis of neutrophil functions of systemic lupus erythematosus]. AB - Flow cytometric quantitative methods of (1) phagocytosis and (2) oxidative product formation by neutrophils were investigated by using whole blood. The neutrophil function of systemic lupus erythematosus (SLE) patients was analyzed by these methods. Kinetics of phagocytosis were investigated by using 1.97 microns fluorescent carboxylated microspheres (Polyscience, USA). The rate of phagocytosis (P) was increased logarithmically according to the T/C (target particle-to-cell) ratio (P = K1 x log (T/C ratio) +K2 K1, K2: constant). The value of Ph 50 were defined as the value of T/C ratio at which rate of phagocytosis was 50%. The PH 50 in SLE patients were statistically higher than in normal controls, which indicated the decreased phagocytic activity in SLE. Active SLE serum increased Ph 50 more than inactive SLE serum, and heat inactivated normal serum (30 min at 56 degrees C) increased Ph 50. Amount of oxidative products of neutrophils was measured by using dichlorofluorescein (DCF), which was converted from dichlorofluorescin diacetate (DCFH-DA) in the cells. After pre incubation in room temperature from sampling to assay, the DCF fluorescent intensity of neutrophil of a normal control was low and revealed one-peak histogram, but that of SLE neutrophils revealed two peaks in histogram. The 2nd peak of high fluorescent intensity was thought to be composed of the subpopulation of neutrophil. The rate of the cells with oxidative products in unstimulated neutrophils was higher in SLE patients than in normal control and correlated with some clinical markers of disease activities. These two flow cytometric methods were rapid and accurate, and the whole blood could be used without separation of neutrophils by these methods. These methods might be useful technique to investigate the neutrophil functions. PMID- 1597302 TI - [Effect of intravenous injection of aspirin on the cochlea]. AB - It is not yet well understood how aspirin acts on the auditory system. This study was aimed at elucidating the effects of aspirin on the cochlear hair cells and cochlear nerve of guinea pigs by recording (1) spontaneous activity of cochlear nerve fibers, (2) compound action potentials (CAPs) evoked by electrical pulses applied to the cochlea through the round window membrane, (3) acoustically evoked action potentials (APs) through the round window membrane and (4) acoustic emissions (sound pressure near the tympanic membrane) evoked by electrical pulses applied to the cochlea. The following results were obtained. (1) After guinea pigs were given aspirin (200 mg/kg) intravenously, a transient reduction in spontaneous activity of cochlear nerve fibers and elevation over the subsequent 10-20 minutes were observed in three of four fibers recorded for more than 30 minutes. The mean spontaneous discharge rate in 102 fibers after aspirin administration (200 mg/kg) was not significantly higher than the control values from 30 to 120 minutes after aspirin administration, while the rate in 112 fibers after aspirin administration (400 mg/kg) was significantly higher. (2) After injecting of 100 mg/kg, 200 mg/kg and 400 mg/kg of aspirin, the amplitude of electrically evoked CAPs decreased significantly, while their latency increased significantly only after injection of 400 mg/kg of aspirin. (3) Changes in the amplitude of acoustically evoked APs and electrically evoked CAPs were compared before and after intravenous injections of 400 mg/kg of aspirin. The AP suppression ratio at low sound intensity was significantly greater than that of CAPs at low and high current levels. (4) After injection of 400 mg/kg of aspirin, the waves of electrically evoked acoustic emissions and their peaks in the frequency analysis disappeared either reversibly or irreversibly. The observed changes in spontaneous activity of cochlear nerve fibers in response to aspirin administration to guinea pigs may represent a tinnitus-like phenomenon. The detection of electrically evoked CAPs suggests that aspirin acts on the cochlear nerve and causes a decrease in its excitability, and the discovery of acoustically evoked APs and electrically evoked acoustic emissions is interpreted as indicating that aspirin acts not only on the cochlear nerve but also on cochlear hair cells. PMID- 1597303 TI - [A study of auditory screening in infant by evoked otoacoustic emission (EOAE)]. AB - The EOAE measuring system was newly developed for infants and the clinical study of the auditory screening for large number of infants using this system was reported. The EOAE measuring system for adults was adjusted as the system for infants. The more compact recording probe than that for adults was prepared. The noise of breathing sound and body movement were rejected during measurements by the artifact rejection system of the signal processor. ABR and EOAE were measured in 166 ears of 85 infants suspected of hearing loss ranging in age between 5 days and 5 years. Twenty-nine infants' EOAEs were measured under awaking. 1.5kHz short tone bursts (35dBnHL and -10dBnHL) was used for stimulating sound in EOAE measuring, and the 100-300 epochs were averaged. The positive response in EOAE was judged by the presence of the obvious peak in 8-10ms after stimulation and confirmation of the reproducibility of this response. The responses evoked by the two different stimulations were also compared for accurate judgement. Ninty-five ears with hearing loss over 35dB in ABR were detected no responses in EOAEs on 35dBnHL stimulation. Fifty-nine ears judged as normal hearing within 30dB in ABR showed good responses in EOAEs, but 6 ears judged as normal hearing in ABR were detected no responses in EOAEs, but 6 ears judged as normal hearing in ABR were detected no responses in EOAE. The latter 6 ears were suspected of secretory otitis media in following examinations. Three cases with abnormal waveforms judged as "unevaluable" in ABR showed good responses in EOAEs indicating their normal cochlear functions. EOAE measurement in infants was easy, speedy and noninvasive. Moreover, the response of EOAEs was clearly obtained with accuracy. Considering these facts, EOAE is suitable examination for detection of hearing impairment and is a useful auditory screening in infants. PMID- 1597304 TI - [In vivo 1H and 31P NMR spectroscopy of the developing rat brain]. AB - Postnatal development of mammalian brain is characterized by cell proliferation, migration, and differentiation of both neuronal and glial elements. These development process are accompanied by not only morphological changes but also biochemical changes. Nuclear magnetic resonance (NMR) spectroscopy is unique in its capability in obtaining metabolic information. In particular water-suppressed proton (1H) spectroscopy is a powerful tool that can be used to quantify certain intracellular amino acids and lactate. However, to date, no systematic analysis of the metabolic changes associated with brain development utilizing in vivo proton spectroscopy has appeared in the literature. In this study, we performed a non-invasive systematic investigation of the biochemical changes associated with brain maturation in the rat during the first 28 days postnatal in vivo utilizing both 1H and 31P spectroscopy. Phosphocreatine (PCr) was found to increase linearly during this period of development. Phosphomonoester (PME) was high at birth, peaked around the 10th day birth, and declined thereafter. N-acetyl-l aspartate (NAA) was low at birth, increased in an approximately linear fashion, and reached adult levels by about day 28 postnatal. Choline was high at birth and showed a two step decline, at approximately day seven and day 20 postnatal. Taurine, a sulfur amino acid abundant in fetal brain, was also present in high levels on the first day postnatal. PMID- 1597306 TI - Data watch. Hospital philanthropy declined in 1991. PMID- 1597305 TI - [Positive selection of a T cell repertoire during intrathymic differentiation]. AB - In SWR mice most of thymocytes bearing a high density V beta chain of T cell antigen receptor (TCR), V beta 17a brightly positive cells, were biased to CD4+8- subpopulation, whereas such thymocytes from SJL mice resided in both CD4+8- and CD4-8+ subpopulations. To elucidate the mechanism underlying the apparent difference in the thymocyte population, CD4/CD8 phenotype of thymocytes bearing high V beta 17a was analyzed in bone marrow (BM) chimeras in which SWR or SJL mice were used as BM donors and various strains of mice as recipients. When SWR precursor cells developed in SJL or B10 thymus, the proportion of V beta 17a+CD4 8+ thymocytes was expanded to the level of that seen in normal SJL mice. By contrast, the proportion of SJL derived V beta 17a+ CD4-8+ thymocytes which had developed in SWR or DBA/1 thymus was reduced to the level of that in normal SWR mice. An intermediate proportion was observed when SWR precursor cells had developed in the thymus of B10.A(4R). It was revealed that H-2K molecules expressed on thymic epithelial cells is one of the determinants which influence the proportion of V beta 17a+CD4-8+ thymocytes. In addition, a hierarchy of selective pressure among the different H-2K haplotypes was present, such as Ks,b greater than Ks/q,k greater than Kq. Fine analysis of the H-2K molecules in which several kinds of H-2Kb mutant (bm) mice were used as recipients to prepare bone marrow chimeras demonstrated that substitutions of amino acids at a region on the beta-pleated floor of antigen recognition site reduced significantly the proportion of V beta 17a+CD4-8+ cells. According to the three-dimensional class I structure, TCR are unable to access directly to this region. Thus, the present finding suggests that the substitutions of amino acids at this site alter the shape and charge of peptide binding site of H-2K molecules and eventually influence the positive selection of the V beta 17a+ T cell repertoire during differentiation. PMID- 1597307 TI - CEO pay. Public scrutiny and pay for performance are the new ground rules. PMID- 1597308 TI - CEOs: there's no simple cure for billing and pricing woes. AB - Hospital billing and pricing practices are drawing increasing heat from lawmakers, employers and consumers. In a four-part package, we explore various aspects of this issue. First, an overview. With public dissatisfaction growing, leaders on Capitol Hill are delving into hospital administrative costs and practices as never before. Second, the pricing controversy. Hospitals have three antidotes to the problem: streamline their charge structures, keep prices closely tied to costs, and explain the complexities of cost-shifting to businesses. Many hospitals are already moving forward on this. On page 29, the consumer angle. While a number of lawsuits in Florida have alleged overcharging by hospitals, Nevada has begun operating a new commission charged specifically with arbitrating patient billing disputes. On page 31, the receivables management story. Hospitals must carefully examine the efficiency of all their business office functions to make billing and collection improvements, experts say; relying on automation alone will not work. PMID- 1597309 TI - Growth of self-funded plans sets hurdles for state reform efforts. PMID- 1597310 TI - CEOs say hospitals must learn from each other for TQM success. PMID- 1597311 TI - Hospitals review ortho process to trim costs. PMID- 1597312 TI - Getting nurses to adopt patient care computers. PMID- 1597313 TI - Hospitals should benefit from new geriatrics plan. PMID- 1597314 TI - AHA lists hospital merger activity for 12-year period. PMID- 1597316 TI - The billing office and the CEO. PMID- 1597315 TI - Telling the public the real health cost story. AB - The real causes of hospital cost increases originate with societal problems like poverty, lack of education, drug abuse, and violences, the author contends. In addition, rampant consumerism and an irrational delivery system play a part in cost increases. Health care professionals need to understand these causes and be able to explain them to their acquaintances outside the field, the author says. PMID- 1597317 TI - The path of memory B-cell development. PMID- 1597318 TI - Maturation and dispersal of B-cell clones during T cell-dependent antibody responses. AB - Germinal centers develop in follicles during TD antibody responses in the first 3 wk following each immunization. In primary responses to protein-based antigens, T cell help is limiting, follicles develop towards the end of the 1st wk from immunization and the size of the follicular response in relatively small. When T cell help is provided the primary B-cell response in follicles is much larger, B cells start to proliferate in follicles within a few hours of immunization and reach peak size 3-4 d later. Available evidence suggests that virgin B cells that colonize follicles to form germinal centers must first be activated by antigen outside follicles, probably in T zones. Memory B cells also proliferate in follicles and they can do so without first being activated outside follicles. Germinal center formation consists of an initial phase of exponential proliferation of B cells within the follicular dendritic cell network. After a single immunization the follicular response is oligoclonal and on average only 3 cells colonize each follicle. In responses to hapten-protein in rats primed previously with the carrier protein these 3 cells increase to around 10(4) cells in 3 d with a cell cycle time of about 6 h. At the end of the period of exponential growth of B blasts, the classical structure of germinal centers emerges. The B blasts become centroblasts in the dark zone of the germinal center which develops at that pole of the FDC network nearer the T zones. The centroblasts are still in rapid cell cycle but do not more than sustain their numbers. The rest of their progeny move to the heart of the FDC network where they come out of cell cycle as centrocytes. Evidence is cited which indicates that somatic mutation occurs in the Ig V-region genes of centroblasts and that centrocytes are selected on the basis of their ability to respond to antigen held on FDC. Centrocytes not receiving this antigen-dependent signal kill themselves by apoptosis. Centrocytes positively selected by interaction with antigen on FDC receive further signals which induce the cells to differentiate to become either plasma cells or memory B cells. The nature of some of these differentiation signals is described. It is shown that proliferation, selection and differentiation occur within germinal centers in distinct micro environments.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597319 TI - Cellular interactions in the germinal center: role of adhesion receptors and significance for the pathogenesis of AIDS and malignant lymphoma. AB - The germinal center forms a specialized microenvironment that is thought to play a key role in the induction of antibody synthesis, affinity maturation of B cells, isotype switching, and memory B-cell formation. Moreover, the germinal center may also be involved in the maintenance of T-cell memory. In this paper we focus on the role of adhesion receptors in cellular interactions in the germinal center, and discuss evidence indicating that these molecules play an important role in regulating B-cell activation and differentiation. Furthermore, we discuss two important diseases involving the germinal center, i.e., HIV infection and malignant lymphoma. In HIV infection, destruction of the FDC network may explain the selective loss of memory cells observed in otherwise asymptomatic patients and is likely to represent a major pathway leading to AIDS. In follicular lymphoma, escape from physiological apoptosis in the germinal center by overexpression of Bcl-2 appears be a major pathogenetic pathway. PMID- 1597320 TI - The development of B cells and the B-cell repertoire in the microenvironment of the germinal center. PMID- 1597321 TI - Signals involved in germinal center reactions. AB - Many of the features observed in the in vitro cultures discussed in this review coincide with characteristics described for an in vivo germinal center response. FDC and T cells are required to maintain B-cell proliferation which is confined to a finite amount of time (i.e. less than 2 wk). Large cellular aggregated form which contain many blasting cells undergoing DNA synthesis. In addition to proliferation, apoptosis is also occurring in the cultures but appears to be limited to the population which is not in contact with the FDC. The system can be driven by specific antigen, suggesting that clonal expansion is occurring. As in other immunological systems, there is an important role for adhesion molecules both for cluster formation and DNA synthesis. Antigen processing and presentation is a major event since blocking this through several mechanisms ends the stimulation. The role of T cells is essential both in vivo and in vitro; however, their exact contribution is still not well understood. It is interesting that blocking IL4 usage either by neutralizing the molecule or its receptor by monoclonal antibodies has no effect on the system. Which interleukins are important for germinal centers remains on open question. Evidence continues to accumulate on the important role of FDC and the molecules they express. Not only are the immune complexes an essential part, but it seems that molecules yet to be defined have an effect. For many practical reasons these have remained a mystery, but using our various systems we are attempting to reveal them. Two intriguing questions which remain include: 1. the molecular nature of the signalling between the FDC and B cell; and 2. how does the FDC retain the antigen in a native form for such long periods of time? An understanding of both mechanisms will provide us with a better appreciation for the events leading to a germinal center response and the immunological phenomenon referred to as memory. PMID- 1597322 TI - De novo germinal center formation. PMID- 1597323 TI - Germinal centers and antibody production in bone marrow. PMID- 1597324 TI - Estrogen & progesterone receptors measurement in breast cancer with enzyme immunoassay & correlation with other prognostic factors. AB - Estrogen and progesterone receptor (ER and PgR) estimation was carried out by an enzyme-immunoassay by a 'sandwich' technique using two different monoclonal antibodies against each receptor on 508 consecutive breast cancer samples. 43.9 per cent of the tumours were ER+ve and 26.6 per cent were PgR+ve; 23.8 per cent were both ER and PgR+ve, 53.3 per cent were both ER and PgR-ve, 20.0 per cent were ER+ve PgR-ve and 2.8 per cent were ER-ve PgR+ve. Both ER and PgR positivity was associated with increasing age, and this was seen within both pre and post menopausal subgroups. Grades I and II tumours were more often ER and PgR+ve compared with grade III tumours, indicating that receptor positivity is a marker of a more well differentiated tumour phenotype. Receptor positivity was higher in primary tumours compared to that in metastatic tissues. The proportion of tumours that was ER+ve was found to vary among the four major religious communities, viz., Hindu, Muslim, Christian and Parsi, and this variation was significant in the overall analysis (P less than 0.01). The Christians had the highest rate of ER+ve tumours while the Muslims had the lowest rate. No correlation was observed between ER and PgR status and axillary nodal involvement or tumour size, suggesting that ER and PgR are independent prognostic factors in breast cancer. We found the EIA method to be an easy and rapid technique for ER and PgR analysis and which requires a small amount of tissue and does not involve the use of radioisotopes. PMID- 1597325 TI - Etiology of febrile episodes in children with acute lymphocytic leukaemia. AB - In 53 children (aged 5 months to 11 yr) with acute lymphoblastic leukemia, 68 febrile episodes were investigated for determining the etiology. Microbial organisms were isolated in 33 episodes. Bacteraemia was seen in 24 patients and in three of them Clostridium species were isolated. Escherichia coli was the commonest isolate and was seen in 11 (18.6%) febrile episodes. Other common organisms isolated were Staphylococcus aureus in nine (15.2%), and Klebsiella pneumoniae and coagulase negative Staph. in 6 (10.2%) episodes each. Pseudomonas aeruginosa and Acinetobactor were isolated in 5 (8.5%) episodes each. PMID- 1597326 TI - Protective & risk DR phenotypes in Asian Indian patients with rheumatoid arthritis. AB - This study of 168 north Indian patients with rheumatoid arthritis (RA) confirms the significant association of susceptibility to RA with DR4 specificity (P less than 0.0001). This association was observed equally in familial as well as sporadic patients. The HLA-DR2 and DR5 alleles were identified to be conferring protection in RA, DR5 being reduced significantly in the non-familial patients only. None of the other DR antigens revealed any association with RA in this population, including the DR4 negative group of patients. An analysis of the DR phenotypes in patients and controls revealed that DR4 in combination with DR1 provided the highest relative risk (71.9) followed by DR4, DR4 (RR = 4.1). These results demonstrate that susceptibility to RA is not due to a single HLA specificity but the effect of a group of related epitopes occurring in common among subtypes of DR4 as well as in some DR1 alleles. PMID- 1597327 TI - Immunoreactivity with S100 protein as an indicator of pregnancy. AB - The usefulness as a pregnancy marker, of immunoreactivity with S100 protein antiserum in endometrial curettings and fallopian tubes during pregnancy was assessed. Twenty six placental tissues of various gestational age, two hydatidiform moles and four fallopian tubes removed for ectopic pregnancy were stained with S100 protein polyclonal antiserum by immunoperoxidase technique. Strong immunostaining was found in glands within the decidua and epithelial cells of fallopian tubes during early pregnancy. However, no S100 protein could be demonstrated in the endometrium in various phases, endometrial carcinomas, decidual glands beyond 12 wk of gestation and normal fallopian tubes. The results indicate a relationship between S100 protein and early pregnancy. Positive immunoreactivity with S100 protein antiserum in the decidual glands and fallopian tube epithelium may help in confirmation of doubtful cases of pregnancy. PMID- 1597328 TI - Atmospheric temperature & anovulation in south Indian women with primary infertility. AB - An attempt at correlating atmospheric temperature, humidity and histologically diagnosed anovulatory endometrium has been made. A total of 140 women who had anovulatory endometrium among 1036 patients who had a clinical diagnosis of primary infertility, over a 5 yr period were studied. The principle of Edwards' test was used to analyse the seasonal trends and the seasonal index for the occurrence of anovulatory endometrium, atmospheric temperature and humidity was calculated using the average percentage method. The results suggest that anovulatory cycles in women with infertility tended to occur more during those months in the year when temperature increased (r = 0.63). However, humidity was not related to anovulation. PMID- 1597329 TI - Evaluation of a home care programme for the mentally retarded children through training of the mother. AB - Mothers of 80 children of mild (IQ 50-70) and moderate (IQ 35-49) mental retardation were selected for the present study. A carefully developed home training programme was utilized to train half of the mothers, the other half forming the control group for the study. The experimental and the control groups were matched for age and IQ of the children, and age of the mothers. The women also did not differ significantly on base-line marital adjustment and parental attitude scores and the experienced social burden of the mothers. In the experimental group there was a significant increase in the IQ and improvement in the behaviour of the children and significant improvement in the marital adjustment score, parental attitude and social burden felt by the mothers. There was no significant change in the control group in any of these variables. PMID- 1597330 TI - Organ weights in autopsy cases from an urban apex hospital. AB - The available limited anatomical and physiological data have been compiled for Indian adult as a part of ongoing efforts in the country to formulate an Indian Reference Man for radiation protection purposes. The parameters included weight, height, body surface area, weight of various organs (brain, heart, kidney, lung, liver etc.), total body water, extra-cellular water, blood volume, specific gravity, total lung capacity, vital capacity etc. The data have been drawn from post-mortem studies (566 males and 185 females) and other data from published work on 433 healthy male and 137 female volunteers. Data gaps have been filled by the method of pooling wherever necessary. This paper presents the intercomparison of the present data with the data available from other sources. The data from various Indian sources indicate a similar trend. However, a significant difference (P less than 0.01) was observed in organ weights and total body weights, in comparison to the Bhabha Atomic Research Centre (BARC) values. The present data are not comprehensive enough to suggest definitive norms of the Indian Reference Man. PMID- 1597331 TI - Importance of periodic measurements in evaluating feeding programmes. AB - Attempts were made to show that periodic measurements are important for evaluating impact of feeding programmes as considerable "within variation" in increments exists which cannot be overlooked. From two socio-economic classes two kindergartens were selected one of which was implementing a feeding programme while the other was not. A total of 273 children were measured for weight and height, three times during the period of 7 months. Normal children showed significant gain in weight while malnourished children showed significant gain in height. The significance in weight (or height) increment at the end of the feeding programme did not necessarily mean that the significance could be obtained in each period even of equal time interval. Simple and cross correlations in increment revealed that weight increment in one period was significantly associated with height increment in the following period suggesting alternating priorities of the body for growth. Carefully planned longitudinal growth studies are therefore necessary for better understanding of growth process and thereby for proper evaluation of feeding programmes. PMID- 1597332 TI - Effect of skim milk on progression of atherosclerosis in cholesterol-fed rabbits. AB - Effect of skim milk on progression of atherosclerosis was studied in cholesterol fed rabbits. Rabbits were given a high cholesterol food (0.5%) with skim milk powder (16%) or no milk (control group). At 12 wk, the plasma cholesterol level was significantly higher in the control group (1605 mg/d1) than in the milk-fed group (1146 mg/d1). The contents of esterified cholesterol and elastin in the aorta were higher in the control group than in the milk-fed group by 28 an 94 per cent, respectively. The differences between the two groups in the contents of aortic triacylglycerols, mucopolysaccharides, collagen and unesterified cholesterol were not significant. The difference in sudanophilic area in the aorta between the control (35%) and the milk-fed groups (31%) was not significant. However, intimal proliferation and medial involvement in the aortic lesions were more severe in the control group. These findings suggest that skim milk can slow down the process of cholesterol induced atherogenesis. PMID- 1597333 TI - Influence of serum albumin & total protein on fructosamine measurement. AB - To assess the effect of serum albumin and total protein on the fructosamine level 57 hypoalbuminaemic patients (serum albumin less than 30 g/1), of whom 44 were nondiabetics and 13 were diabetics, were studied. Fructosamine levels of hypoalbuminaemic diabetics was increased only marginally in comparison to healthy controls (P greater than 0.05) whereas in 122 other normalbuminaemic diabetics, the level was found to be significantly higher (P less than 0.001). In control subjects, the correlation between fructosamine and serum albumin (r = 0.69, P less than 0.001) was better than that of total protein (r = 0.42, P less than 0.01) whereas in hypoalbuminaemic patients the pattern was reversed (r = 0.51 and 0.59 respectively), indicating substantial contribution by the globulins. A working formula suggesting approximate contribution of each gram of albumin and globulin in healthy subjects was calculated. It is inferred that the use of serum fructosamine for assessment of glycaemic status could be misleading in patients with lower albumin values. Calculating serum fructosamine values from serum albumin alone in these patients is likely to be inaccurate, as it ignores the contribution of globulins which can be substantial in certain disease conditions. A gross idea regarding the glycaemic status can be obtained by comparing actual and calculated values of fructosamine from the formula. PMID- 1597335 TI - Morphometry of mitochondria in the choroidal ependyma of hydrocephalic guineapigs. AB - Fifteen young guineapigs were made hydrocephalic by intracisternal injection of kaolin and 16 guineapigs were used as control. Volume, number and surface areas of both the outer and inner membranes of the mitochondria of the choroidal ependyma of these animals were studied, using a coherent multipurpose test system. Volume, number and surface area of the outer membrane of the mitochondria did not show any significant difference between the two groups. However, surface area of the inner membrane of the mitochondria including cristae showed a significant decrease in the hydrocephalic animals. This reduction in the surface area could probably be attributed to the reduced activity of the choroidal ependymal cells in obstructive hydrocephalus. PMID- 1597334 TI - Effect of acute & chronic imipramine treatment on glucose homeostasis. AB - Single dose of imipramine (IMI) produced significant (P less than 0.05) hyperglycemia in rabbits, the effect peaking at 1 h. The hyperglycemic response was less marked in rabbits which were chronically pretreated with IMI for 4 wk. Simultaneous administration of insulin, oral glucose or adrenaline with single doses of IMI resulted in an enhancement of usual hypoglycemic/hyperglycemic responses of these agents. However, when these drugs were administered in chronically IMI fed animals there was complete reversion of the enhancement. Daily administration of adrenaline for further 6 days with IMI feeding in the chronically IMI treated rabbits, led to enhancement in the hyperglycemic response to adrenaline (P less than 0.001). In contrast, similar administration of insulin resulted in reduced hypoglycemia. Further, glucose feeding with IMI plus adrenaline or insulin in these animals did not result in any significant alteration in blood glucose level (BGL), as compared to oral glucose plus single doses of adrenaline or insulin. GTT done on the day next to drug treatment in rabbits chronically pretreated with IMI and than with IMI plus insulin, produced an enhanced hyperglycemic response, as compared with the control group (P less than 0.01). These observations indicate that acute (but not chronic) treatment with IMI not only produces a rise in BGL per se but also enhances the response to other agents which affect glucose homeostasis. PMID- 1597336 TI - Incidence & immunological profile of multiple myeloma patients. AB - Multiple myeloma was diagnosed in 84 residents of Jammu & Kashmir between 1984 1988. The data were analyzed for variations of demographic factors, ethnicity and location of residence (urban/rural). The average annual incidence per 100,000 residents was 1.28. The rates for males and females were 2.02 and 0.71 per 10(5) persons/year respectively. The average incidence rate for Muslims was significantly higher than that for Hindus. Urban residents had significantly higher rates than rural population. Highest incidence rate (14.39) was in the age group of 65 yr and above. PMID- 1597337 TI - Physiology: a turning point. PMID- 1597338 TI - EEG spectral power reduction and learning disability in rats exposed to lead through postnatal developing age. AB - The present study was carried out to assess electrophysiological and behavioral changes in Wistar rats caused by consuming a daily dose of lead acetate (400 micrograms lead/g body weight/day, given by gastric intubation, from second day of birth to 60 days of age. At 60 days of age, the lead treated rats showed in both wakeful and slow wave sleep stages, a statistically significant reduction in the delta, theta, alpha and beta band EEG spectral power in motor cortex (MC) and hippocampus (HI) with the exception of the delta and beta bands power of MC in wakeful state (WA). Lead administration was discontinued after that age for allowing rehabilitation for 40 days. Then, operant behavioral assessment was done. Results revealed that the lead treated animals took significantly more time and sessions than control normal animals in attaining criterion of learning. Hence exposure to lead in early age could result in a learning disability persisting even after discontinuation of exposure. PMID- 1597339 TI - Evidence for nootropic effect of BR-16A (Mentat), a herbal psychotropic preparation, in mice. AB - BR-16A (Mentat 50-500 mg/kg) improved acquisition and retention of a passive avoidance task in a step-down paradigm in mice. BR-16A (50-500 mg/kg) reversed scopolamine (0.3 mg/kg)-induced disruption of acquisition and retention. BR 16-A (50 and 100 mg/kg) attenuated amnesia produced by the acute treatment with electroconvulsive shock (ECS), immediately after training. Chronic treatment with ECS, for 6 successive days at 24 h interval, disrupted memory consolidation on the 7th day. Daily administration of BR-16A (50 and 100 mg/kg) for 6 days significantly improved memory consolidation in mice receiving chronic ECS treatment. BR-16A (20-500 mg/kg), administered on the 7th day, also attenuated the disruption of memory consolidation produced by chronic treatment with ECS. On elevated plus-maze, BR-16A (50 and 100 mg/kg) reversed scopolamine (0.3 mg/kg) induced delay in transfer latency on the 1st day. The above data suggests a nootropic effect of BR-16A in naive and amnesic mice. PMID- 1597340 TI - Protective effect of propranolol on ethanol-induced gastric lesions in rats: probable mechanism of action. AB - The non-selective beta-adrenoceptor antagonist, propranolol, has been reported to protect against gastric injury in mice, an effect only partly due to prostaglandin release. This study was designed to confirm the gastric cytoprotective effect of propranolol in another species of animal, the rat, and investigate further its mechanism of action. Our results show that propranolol prevents both ethanol-induced gastric lesions as well as ethanol-induced contraction of the circular muscle of rat fundic strip. The local anaesthetic, lignocaine also inhibited the effect of ethanol on circular muscle. However, timolol, another non-selective beta-adrenoceptor antagonist, failed to produce such an action. The effect of propranolol was abolished by the cyclooxygenase inhibitor, indomethacin and a high dose of the guanylate cyclase inhibitor, methylene blue. The results suggest that in addition to prostaglandins, endogenous nitric oxide and the membrane stabilising action of propranolol may also be involved in its gastroprotective action. PMID- 1597341 TI - Antiepileptic drugs delay the onset of seizures induced by aminophylline in conscious rats. AB - Aminophylline, 285.7 +/- 2.19 mg/kg infused intravenously in unanaesthetized rats produced onset of seizures within 3.2 +/- 0.99 minutes. Seizures were repetitive and death occurred in 10.5 +/- 1.75 minutes. Pretreatment of rats with carbamazepine, sodium valproate and diazepam at doses that prevented electroshock induced seizures were effective in significantly postponing seizures and death, but did not reduce mortality. Concomitant EEG studies in aminophylline infused rats showed that cortical excitability evidenced by initial cortical spiking occurred at 42 secs and polyspiking at 165 seconds. Following diazepam, the initial cortical spike was delayed 50 fold, appearing after 36 minutes. Antiepileptic drugs and EEG monitoring may prove useful in patients with status asthmaticus receiving intravenous aminophylline. PMID- 1597342 TI - Reversal of changes of myocardial lipids by chronic administration of aspirin in isoproterenol-induced myocardial damage in rats. AB - The effect of aspirin on isoproterenol-induced changes related to myocardial damage was studied in rats. Rats were treated with aspirin (1.2 mg/100 g/day) orally, daily for a period of one month. Isoproterenol (20 mg/100 g, sc, twice at an interval of 24 hr) was administered. In isoproterenol treated rats marked increase in cholesterol, free fatty acids and triglycerides in both serum and heart were observed. The phospholipid level was lowered in heart with significant increase in serum in isoproterenol treatment. Serum LDL cholesterol was found to be increased with a significant decrease in the level of HDL cholesterol with enhanced level of lipid peroxides in heart. Aspirin showed marked reversal of these metabolic changes induced by isoproterenol. PMID- 1597343 TI - Pulmonary function studies in Gujarati subjects. AB - In this study a multiple regression equation for prediction of ventilatory pulmonary function tests (FVC, FEV1%, FEF25-75% and PEFR) is developed in average healthy non-smoker male and female Gujarati subjects. The average adult female values showed a reduction varying from 21.0 to 29.0% compared to adult male subjects. There is a deviation of the present study values from other studies in Indian subjects and values from European studies are higher than the present values. This study demonstrated that the present regression equation is the most ideal and appropriate for prediction of pulmonary function values in Gujarati subjects either for assessing physical fitness in normal subjects or for determining the pattern of ventilatory impairment in respiratory disease patients. The pulmonary function values assessed by substituting the average age, height and weight of females in male regression equation revealed lower values in females ranging from 14.0 to 19.0% attributable only due to difference in sex. PMID- 1597344 TI - Effect of vesical feedback on rate of urine formation demonstrated by infusing hypotonic and hypertonic saline into the urinary bladder of dogs. AB - The present study was undertaken to investigate the effect of the presence of solutions of different osmolality (hypertonic 3%, 4% and 5% hypotonic 0.1%, 0.2% and 0.3% in the urinary bladder on renal urine formation. The study was conducted on 36 dogs of either sex. 100 ml normal saline was used for distending the bladder. Various hypertonic and hypotonic solutions were infused inside the bladder and rate of urine formation was recorded. Presence of hypertonic fluid increased the rate of urine formation and hypotonic fluid decreased it. PMID- 1597345 TI - Interleukin-2: a possible trigger for autoimmunity. AB - High doses of recombinant interleukin-2 (IL-2) may induce autoimmune lesions in patients receiving experimental cancer treatment. In most cases, the manifestation of autoaggression is transient and organ-specific, predominantly affecting the thyroid gland. Only a fraction of the patients are concerned; most individuals (around 90%) do not develop any signs of autoimmunity. Apparently, endogenously hyperproduced IL-2 may also be implicated in the pathogenesis of autoaggression, since active phases of such disparate autoimmune diseases, like multiple sclerosis and systemic lupus erythematosus, are accompanied by elevated IL-2 serum levels. Taking into account that immunological self-tolerance is maintained by several distinct mechanisms, we investigated whether IL-2 would interfere with clonal deletion or clonal anergy in vivo. In several experimental systems, IL-2 failed to abolish clonal deletion in the murine thymus or in the peripheral T-cell compartment. IL-2 did not affect the clonal deletion of self reactive B cells in the bone marrow either. In contrast, IL-2 was found to be effective in abrogating clonal anergy of non-deleted self-specific T cells. Only in the presence of high frequencies of self-specific, potentially autoreactive T cells, IL-2 induces autoimmune lesions. Thus, IL-2 interferes with a mechanism of self-tolerance that guarantees the inactivation of T cells that for some reason have 'escaped' clonal deletion. If these data, obtained in the murine system, are extrapolated to man, then it may be stated that the T-cell repertoire of most individuals has been completely purged from self-reactive cells. Only in the presence of a non-deleted, anergic, potentially auto-reactive T-cell population, could organ-specific disease be induced by IL-2. PMID- 1597346 TI - Development of a concomitant nickel and chromium sensitization model in the guinea pig. AB - Although nickel allergy is the most frequent contact hypersensitivity in man, reports on successful nickel sensitization in experimental animals are scarce. Chromium hypersensitivity, on the other hand, is readily induced in guinea pigs. In this study we set out to obtain reproducible nickel sensitization in guinea pigs, in order to establish an animal model for immunospecific tolerance and desensitization studies in which two non-cross-reacting metal allergens, chromium and nickel, could be studied simultaneously. Strong and reproducible sensitization to nickel was achieved by injecting low amounts of Freund's complete adjuvant and nickel sulfate in a split-adjuvant procedure. Strong erythematous reactions were observed as early as 14 days after sensitization and could be elicited both by intradermal and open epicutaneous challenges. Optimal evaluation was with nickel sulfate administered epicutaneously in 40% dimethyl sulfoxide to enhance skin penetration. Hypersensitivity could be transferred with lymphocytes and not with serum. Sensitization procedures for nickel and chromium then could successfully be combined in a double sensitization procedure. With four different guinea pig strains no genetic restriction was observed for the induction of nickel or chromium sensitivity. However, for both metals a clear sex and age dependence was observed: female guinea pigs reached a higher degree of sensitization than males, whereas sensitization in young animals was relatively weak. PMID- 1597347 TI - Relationships between exposure to spores from Rhizopus microsporus and Paecilomyces variotii and serum IgG antibodies in wood trimmers. AB - A longitudinal study of wood trimmers exposed to mould spores was carried out from 1985 to 1988. Exposure to airborne spores from Rhizopus microsporus ssp. rhizopodiformis and Paecilomyces variotii was measured by scanning electron microscopy of filter samples. Specific IgG antibodies to these moulds were measured by ELISA in serum samples collected at half-year intervals. Antibody levels to R. microsporus and P. variotii were higher in wood trimmers than in other sawmill workers whose jobs had an assumed lower exposure to mould spores. Antibody levels were significantly elevated after periods with high exposure compared to antibody levels in the same wood trimmers after periods with low exposure. Antibodies were also found in newly employed wood trimmers. These wood trimmers were exposed to 1,300 x 10(3) R. microsporus spores/m3 and 130 x 10(3) P. variotii spores/m3 (arithmetic mean exposure). Antibody levels in the newly employed wood trimmers were similar to antibody levels in wood trimmers who had already worked in the trimming department before the start of the study. Antibody levels to R. microsporus and P. variotii in wood trimmers can be regarded as indicators of fairly recent exposure. There were, however, large differences between the individual antibody levels of similarly exposed wood trimmers. PMID- 1597348 TI - Human peripheral blood hypodense eosinophil proteins are more labeled with 32P than the normodense eosinophil proteins. AB - Peripheral blood eosinophils from patients with atopic dermatitis and normal healthy controls were isolated on a Percoll gradient and were incubated with [32P]orthophosphoric acid. After stopping the reaction, SDS/PAGE was performed and autoradiographs were prepared to determine the incorporation of 32P into proteins. Eosinophils developed at least 14 protein bands below 66.2 kDa by SDS/PAGE and the differences of the protein staining patterns between hypodense and normodense eosinophils were present. In the autoradiographs five distinct radioactive bands were observed below 31 kDa. 32P incorporation into the bands of hypodense eosinophils was stronger than that of normodense eosinophils, suggesting possible involvement of protein phosphorylation in the activation process of human eosinophils. PMID- 1597349 TI - Diagnosis of grass pollen allergy with recombinant timothy grass (Phleum pratense) pollen allergens. AB - In order to establish a test system for grass pollen allergy based on the use of recombinant allergens we chose timothy grass (Phleum pratense), a widely spread grass, as a model. From a lambda gt11 cDNA expression library that we had constructed from pollen RNA of timothy grass (P. pratense), we had obtained with serum IgE from a grass pollen-allergic individual 60 IgE-binding clones. By differential testing with sera from different grass pollen-allergic patients, we selected three distinct clones encoding Phl p I (group I), Phl p V (group V) and profilin from timothy grass, which when used together allowed the diagnosis of grass pollen allergy in 97 out of 98 tested grass pollen-allergic patients employing a simple plaque lift technique. This recombinant test based on plaque lifts containing allergen-beta-galactosidase fusion proteins was compared with IgE immunoblots using crude pollen protein extracts from timothy grass. Both methods were in good agreement with RAST scores and clinical data, and proofed to be useful for the diagnosis of grass pollen allergy. Our results further indicate that a limited panel of only two recombinant grass pollen allergens, Phl p I and Phl p V, together with the plant panallergen profilin could be sufficient for the diagnosis and possibly immunotherapy of grass pollen allergy. PMID- 1597350 TI - Detection of antibodies against streptococcal peptidoglycan and the peptide subunit (synthetic tetra-D-alanyl-bovine serum albumin complex) in rheumatic diseases. AB - Serum antibodies reactive with streptococcal cell wall peptidoglycan (PG) and its peptide subunit (synthetic tetra-D-alanine) were measured by enzyme-linked immunosorbent assay (ELISA) in patients with rheumatoid arthritis (RA), juvenile rheumatoid arthritis (JRA), osteoarthritis and acute rheumatic fever (RF) compared with healthy subjects. Using 'checkerboard' titrations, anti-PG antibody in human serum was detected at a concentration of PG antigen at 10 micrograms per well with serum dilutions of 1:1,000. For measurement of anti-tetra-D-alanine antibody, the antigen, (D-Ala4)31 was used at 0.5 micrograms per well and sera were diluted to 1:200. When the IgG antibody levels to the PG and the tetra-D alanine of the sera of patients with RA, JRA and RF were compared with sera from healthy subjects, the sera of the patients had significantly higher levels than did healthy subjects. Antibody that reacted with the PG in serum was absorbed with purified group-specific C-carbohydrate (A-CHO), but A-CHO was not capable of absorbing anti-(D-Ala4)31 antibodies. Therefore, the peptide subunit should be used as antigen in order to measure the specific antibody to PG. Both anti-PG and anti-tetra-D-alanine antibody in human sera primarily belonged to the IgG2 subclass. PMID- 1597351 TI - T-cell-dependent popliteal lymph node reactions to platinum compounds in mice. AB - The requirements for sensitization to complex salts of platinum were investigated in a mouse model by means of the popliteal lymph node (PLN) assay. A single subcutaneous injection of dissolved hexachloroplatinates without adjuvant induced a vigorous primary immune reaction in the draining PLN. Dose-dependent lymph node activation was determined by an increase in both PLN weight and cellularity. In C57BL/6 mice, peak reactions were obtained around day 6 after administration of 90-180 nmol Na2[PtCl6] or (NH4)2[PtCl6] per animal. Mice primed to [PtCl6]2- mounted an enhanced response upon local restimulation with suboptimal doses of the same but not unrelated compounds, indicating a specific secondary response. T cells were required to elicit PLN reactions to [PtCl6]2-, because athymic nude mice completely failed to respond, in contrast to their +/nu littermates. Differences between various inbred strains of mice revealed that Pt-induced PLN responses are genetically controlled. Moreover, the immunogenicity of Pt salts in mice is not confined to hexachloroplatinates, but other compounds, such as the antineoplastic agent cis-dichlorodiamine platinum, are able to induce comparable PLN reactions. PMID- 1597352 TI - Differential ability of occupational chemical contact and respiratory allergens to cause immediate and delayed dermal hypersensitivity reactions in mice. AB - Trimellitic anhydride (TMA) is known to cause occupational respiratory allergy associated with the presence of specific IgE antibody. Other chemicals, such as 2,4-dinitrochlorobenzene (DNCB), while exhibiting a clear potential for contact sensitization, apparently lack the ability to induce respiratory allergy in man. It has been shown previously that although both chemicals are immunogenic in mice, each provoking contact sensitization, exposure only to TMA results in an IgE antibody response. In the present study, to examine further the characteristics of human allergens, we have compared the ability of TMA and DNCB to elicit immediate and delayed cutaneous hypersensitivity reactions in mice. Topical exposure to both chemicals resulted in delayed (24 h) hypersensitivity. However, only TMA induced, in addition, an immediate (1 h) dermal reaction following local challenge. Serum from TMA-immune mice, but not from untreated mice or mice sensitized with DNCB, was able to transfer immediate hypersensitivity to naive recipients. The kinetics of passive sensitization with TMA-immune serum, together with the fact that immediate hypersensitivity to DNCB could be induced with monoclonal IgE anti-dinitrophenol (DNP) antibody, suggests that the immediate dermal responses caused by TMA are effected by hapten-specific IgE. These data demonstrate that different classes of occupational chemical allergen exhibit a variable potential to elicit immediate and delayed dermal hypersensitivity reactions in mice, and provide a novel approach to the classification and characterization of human allergens. PMID- 1597354 TI - Immunoreactivity of a mammalian liver component with leprosy sera. AB - Sera from 77 leprosy patients in various stages of infection--tuberculoid (TT), lepromatous (LL), borderline tuberculoid and borderline lepromatous--15 contacts and 21 normal healthy individuals, were assayed in an indirect enzyme-linked immunosorbent assay and dot enzyme immunoassay using ethanol-soluble and thermostable extract of liver as the antigen. The highest incidences of reaction were found in untreated LL patients (100%) and in TT patients (91%), while the sera from borderline patients showed a comparatively lower incidence (43%). Some of the sera from contacts of leprosy patients (6/15) also showed high reactivity. Assays using lecithin as an antigen did not exhibit any reaction. PMID- 1597353 TI - Effects of sex steroid analogs on spontaneous autoimmune thyroiditis in obese strain chickens. AB - Treatment of obese strain chickens, either in ovo or after hatching, with testosterone or various testosterone-derived steroid analogs having no or only weak endocrine activities causes significant protection from spontaneous autoimmune thyroiditis occurring in these birds. This effect is not correlated with the endocrinological properties of these steroids. This observation and similar results in other models for autoimmunity may present a basis for a more selective therapy in human autoimmune diseases in that hormonal side effects no longer preclude this approach. PMID- 1597355 TI - Interleukin-8 and neutrophil leucocytes: adhesion, spreading, polarisation, random motility, chemotaxis and deactivation in assays using 'sparse-pore' polycarbonate (nuclepore) membranes in the Boyden chamber. AB - Adhesion, spreading, chemotaxis and deactivation of chemotactic responses of separated human peripheral blood neutrophil leucocytes under the influence of interleukin-8 (IL-8) were tested using a previously described Boyden chamber-type method involving 'sparse-pore' polycarbonate (Nuclepore) filtration membrane. The random motilities of neutrophils in similar concentrations of IL-8 were tested using corresponding chambers with polycarbonate membranes of standard pore densities. In addition, polarisation of neutrophils in suspension in various concentrations of IL-8, and the possibility of deactivation of this polarisation response by IL-8 itself or by N-formyl-methionyl-leucyl-phenylalanine (FMLP) were examined. Neutrophils exhibited maximum chemotaxis to IL-8 in a concentration of 100 ng/ml, and to a degree which was similar to the maximum response to FMLP (10( 7) M). This chemotactic response to IL-8 was markedly reduced by pretreatment of the cells with either 100 ng/ml IL-8 (deactivation) or 10(-7) M FMLP (cross deactivation). On the other hand, the chemotactic response of the neutrophils to FMLP was reduced by pretreatment with FMLP but was not deactivated by pretreatment with IL-8 (i.e. deactivation but not cross-deactivation). Neutrophils in suspension were maximally polarised by 100 ng/ml IL-8, and to lesser degrees by 1, 10 and 1,000 ng/ml IL-8. The detailed morphology of the polar cells was not distinguishable from that induced by 10(-8) M FMLP. Pretreatment of the cells with either IL-8 or FMLP resulted in no reduction of polarisation in response to subsequent exposure to either agent (i.e. neither deactivation nor cross-deactivation).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597356 TI - Familial cardiomyopathy with variable hypertrophic and restrictive features and common HLA haplotype. AB - We describe a familial cardiomyopathy affecting three generations of family members with similar electrocardiographic abnormalities and human leukocyte antigen (HLA) haplotype. Autopsy findings in two of our patients were diagnostic of hypertrophic cardiomyopathy, although surviving affected members do not show ventricular hypertrophy on echocardiography. One patient's echocardiogram revealed giant atria in the absence of ventricular hypertrophy, suggesting a restrictive form of cardiomyopathy. In this kindred, an HLA haplotype appearing in affected, but not in healthy, family members may predict occurrence of disease during its presymptomatic phase in subsequent generations. PMID- 1597357 TI - Morbidity and mortality in 46 patients with the VACTERL association. AB - During a 10-year period, 313 infants were treated at the Hospital for Sick Children for esophageal atresia, of whom 46 had features of the VACTERL association. These 46 patients had a mortality rate of 24%, most deaths being caused by cardiovascular abnormalities. Infants weighing less than 2,050 g had a mortality rate of 26%, double that of heavier infants. During the first year of life there was considerable morbidity resulting from the tracheoesophageal abnormalities. Whenever possible primary repair of the esophagus should be performed; however, many patients with VACTERL association had an unusually long gap between the two ends of the esophagus, and repair under tension was associated with a high incidence of complications. Of the 35 survivors, 25 are in a satisfactory, stable condition, but 10 still require treatment necessitating repeated admission to hospital. Anorectal, renal or skeletal anomalies rarely caused death, but, when severe, were associated with a poor quality of life. PMID- 1597358 TI - Acute symptomatic hernia. AB - Acute symptomatic hernia is a clinical entity characterized by the coexistence of acute incarceration of an abdominal wall hernia together with an acute abdominal disease. Thirteen such cases are described. Increased awareness of this entity, both pre- and intraoperatively, is probably the basis for the improved rate of correct diagnosis (60%) and the decreased mortality (7%). PMID- 1597359 TI - Fatal methemoglobinemia caused by inadvertent contamination of a laxative solution with sodium nitrite. AB - We describe two cases of fatal methemoglobinemia resulting from ingestion of laxative solution inadvertently contaminated with sodium nitrite. Postmortem toxicological examination revealed methemoglobin levels in excess of 75% in both patients--a level that is uniformly fatal. The laxative solution was found to contain sodium nitrite instead of sodium sulphate at a concentration of 15 g/l. The pathophysiology of methemoglobinemia and a review of other reported cases of toxic methemoglobinemia are presented. Marked cyanosis in the face of intact cardiorespiratory function should alert the physician to the possibility of toxic methemoglobinemia. PMID- 1597360 TI - Nalidixic acid-induced hemolytic anemia complicating halothane-induced hepatitis. PMID- 1597361 TI - Eradication of Ureaplasma urealyticum from amniotic fluid. PMID- 1597363 TI - Hereditary complement deficiencies in Israel. PMID- 1597362 TI - The genetics of familial cardiomyopathy. PMID- 1597364 TI - Leukemoid reaction in a patient with pulmonary edema. PMID- 1597365 TI - Prevention of chronic carriage of hepatitis B virus infection in Ethiopian immigrants. PMID- 1597366 TI - [Immunology of leprosy. Review of data from the 1980-1990 time period]. AB - The classification used for leprosy so far distinguishes between two polar forms (pauci-bacillary and multi-bacillary), with different influences on the immune cells. The identification of specific antigens of the germ surface with monoclonal antibodies allows finer differentiation in classification, which now extends to transitional forms of clinical relevance. The current status of knowledge about immunological phenomena triggered by Mycobacterium leprae is complex, and controversy is rife at present. The bacillus is comparable to other mycobacteria in antigenicity. Owing to the complicated composition of the cellular envelope, few epitopes are accessible for immunological reactions. Investigation on the behaviour of T-lymphocytes in combination with analysis of the bacterial surface structures led to the development of a new pathogenetic concept. In spite of different immunological and inflammatory reactions in patients (reflecting the individual pathology), the discrimination between a partial and a total immunological defect is made. So far, no histocompatibility antigen type has been found that allows recognition of the predisposition to infection. Immunity against the bacteria is achieved after BCG in some cases. All this suggests that the development of a vaccine via biotechnical synthesis of idiotypes and anti-idiotypes may be possible. PMID- 1597367 TI - [Experiences with clofazimine therapy of Melkersson-Rosenthal syndrome]. AB - Melkersson-Rosenthal syndrome (MRS) is characterized by the triad of facial paralysis, facial oedema, and lingua plicata in association with other symptoms, such as headache and mental changes. Because the origin of this syndrome is still unknown, only symptomatic treatment is possible. In 18 patients suffering from MRS, whether with a complete or with an incomplete picture, we used the antileprosy drug clofazimine for therapy. A decrease in the frequency and intensity of oedema was achieved by this therapy in 94% of patients. However, improvement persisting throughout a follow-up period of up to 3 years was seen in only 62% of patients. We demonstrate that clofazimine is an alternative to glucocorticosteroids for the treatment of MRS. PMID- 1597368 TI - [Bullous poikilodermatitic amyloidosis of the skin with junctional bulla development in IgG light chain plasmacytoma of the lambda type. Histology, immunohistology and electron microscopy]. AB - A 75-year-old patient presented with bullae, poilokilodermatic skin and nail dystrophy as signs of systemic amyloidosis 1 year before an IgG myeloma of the lambda type was diagnosed. The skin lesions appeared at mechanically irritated locations on the trunk and at the tensor sites of the extremities. Histology showed a subepidermal blister and necrotic keratinocytes in the epidermis. There were amyloid deposits in the papillary dermis perivascular, and in the deep dermis around eccrine glands and in arrectores pilorum muscles. Polyclonal antibodies allowed classification of the deposits as amyloid composed of lambda light-chain immunoglobulins. Electron microscopy revealed globoid deposits of non branching filaments typical of amyloid. The blister was formed at the level of the lamina lucida, with the lamina densa at the base of the bottom of the bulla. So far, junctional blister formation in bullous amyloidosis of the skin has been described only once. Our case is the second report of this blister type, and to our knowledge the first published report of a junctional blister in myeloma associated systemic amyloidosis. PMID- 1597369 TI - [Naevus follicularis keratosus: clinical aspects, histology and histogenesis]. AB - The clinical, histological and histogenetic aspects of naevus follicularis keratosus (NFK) ("naevus comedonicus") are reported. Clinically, NFK appears mostly as linear and unilateral groups of dark comedo-like plugs. Clinical forms include variants with minimal and distinctive deviations from the basic form. Recurrent inflammation is not mandatory. Histological examination reveals keratin filled infundibula, with granular layers that are always present but though not always equally obvious. This finding corresponds to the mode of keratinization in the follicular infundibulum. Overall, the findings are indicative of a harmartoma of the follicular infundibulum with additional rudimentary sebaceous glands. PMID- 1597370 TI - [Typing of infiltration cells in primary, localized, nodular, cutaneous amyloidosis]. AB - Amyloid tumours in two patients with primary localized nodular cutaneous amyloidosis contained very dense infiltrates consisting mainly of plasma cells and lymphocytes. In one case IgM was detected on many cells of the infiltrate, while in the other IgA was found in morphologically apparently normal plasma cells. Immunohistochemical investigations did not reveal any immunoglobulin light chain restriction in either of the tumours. Numerous cells expressed B cell markers, such as CD20 or CD38. Rearrangement studies on material from the amyloid tumour of one of the patients confirmed the monoclonality of plasma cells. This observation indicates that the nodules of primary localized nodular cutaneous amyloidosis indeed represent an extramedullary plasmocytoma, which consists of amyloid-producing plasma cells. Of special interest was the unexpectedly high proportion of cells expressing T cell markers (CD3, CD5, CD4 greater than CD8) in the amyloid nodules of both patients. After excluding co-expression of B and T cell markers on identical cells by immunohistochemical studies on serial sections and also after molecular biological studies, we assume that this is a separate T cell population that may have a regulatory effect on the production of amyloid. PMID- 1597371 TI - [X-chromosome dominant chondrodysplasia punctata (Happle) in a boy]. AB - The case of a newborn boy with ichthyosiform erythroderma, asymmetrical shortening of the femur and sectorial cataract is reported. The hyperkeratotic areas cleared within 2 months, resulting in follicular atrophoderma. The clinical findings and course of the disease, and also the histological and ultrastructural features, indicate an X-linked dominant chondrodysplasia punctata (Happle). Since a normal male karyotype (46, XY) is present, a half-chromatid mutation of the maternal gamete and a somatic mutation are considered as possible explanations for this mosaic phenotype. PMID- 1597372 TI - [Sterile eosinophilic pustulosis (Ofuji)--Mediterranean and endemic case]. AB - Sterile eosinophilic pustulosis (Ofuji's disease) is very rare in Europe compared with Japan. We describe a Turkish and a German case. Clinical and histopathological findings do not allow a clearcut diagnosis. Many differential diagnoses have to be excluded, mainly by histopathological investigations. Careful examination of the heart and other internal organs is also necessary, since Ofuji's disease belongs to the group of hypereosinophilic diseases. Transitions from cutaneous to internal manifestations of hypereosinophilic disease may exist. PMID- 1597373 TI - [Skin symptoms of chronic inflammation of a tooth root apex]. AB - Cutaneous manifestations of a periradicular inflammation are now uncommon. In most cases the periradicular infection results in the development of an apical granuloma. If there is proliferation of resting epithelial cells in this granuloma a cyst will develop, the so-called radicular cyst. A rare form of periradicular inflammation is the so-called chronisch granulierende Entzundung nach Partsch [Partsch's chronic granulomatous inflammation]. In this case the granulation tissue spreads through the bone and results in a cutaneous odontogenic sinus. We report on a female patient in whom complete healing was obtained by removal of the periradicular process and excision of the sinus tract. PMID- 1597374 TI - [Epicutaneous test with amalgam]. PMID- 1597375 TI - [Faun-tail nevus]. PMID- 1597376 TI - [Spring congress of MSSVD and GBGK]. PMID- 1597377 TI - [The epidermal Langerhans cell: watch post of the immune system in relation to the outside world]. PMID- 1597378 TI - Health physics training programs. PMID- 1597379 TI - A retention-excretion model for americium in humans. AB - This paper discusses current information on the biological behavior of americium and describes a biokinetic model for americium in humans. Emphasis is on the time dependent distribution and excretion of systemic americium in the adult, but potential differences with age in parameter values are addressed, and predictive models of absorption of americium to blood from the respiratory and gastrointestinal (GI) tracts are provided in an appendix. The analysis builds on the author's previous biokinetic model for plutonium in humans and recent analyses and/or models of other authors regarding the behavior of americium and related elements in humans and laboratory animals. Compared with the retention model for americium implied in ICRP Publication No. 48, the present model, as applied to adults, yields reasonably similar whole-body retention of americium at all times, much less retention in the liver after a few months, somewhat greater retention in the total skeleton after a few years, and very similar long-term integrated activities of long-lived americium isotopes on bone surfaces. Compared with a previous model of Durbin and Schmidt, the present model, as applied to adults, predicts very similar retention in the liver at all times, somewhat smaller retention in the total skeleton after a few years, and somewhat greater urinary excretion rates at all times after acute uptake to blood. PMID- 1597380 TI - Effectiveness of continuously infused DTPA therapy in reducing the radiation dose from inhaled 244Cm2O3 aerosols. AB - Radionuclide decorporation is the only effective method of reducing radiation dose for persons contaminated accidentally. In this study, dogs that had inhaled a moderately soluble aerosol of 244Cm2O3 were treated with either discrete intravenous injections of the chelating agent diethylenetriaminepentaacetic acid (Zn-DTPA) or with subcutaneous infusion of Zn-DTPA at either 30 or 120 mumol kg-1 d-1. Each treatment regimen was continued for 64 d, whereupon all animals were killed, and collected excreta and tissue samples were analyzed for curium. All DTPA treatment methods were effective. A total of 89% of the initial pulmonary burden (IPB) was removed by DTPA injection, whereas 94% IPB was removed by the low dose of infused DTPA and 97% by the high dose treatment. Thus, low and high infused doses of DTPA prevented the translocation of greater than 99.5% of curium to liver and 97-99% to bone and kidney. The resultant dose reductions to these organs were superior to those achieved by intravenous DTPA injections. PMID- 1597382 TI - Relationship between 131I ground surface contamination activity and gamma spectra above ground. AB - A Monte Carlo calculation of the transport of gamma rays in an air-over-ground geometry has been performed for the case of uniform ground surface contamination by 131I. The scalar fluence rate and dose rate, as well as the energy and angular distributions, have been computed at 31 altitudes ranging from 1-1000 m for a surface contamination of 1 Bq cm-2. PMID- 1597381 TI - Development of a chemical form discrimination system for 14C species in gaseous waste. AB - A new system was developed for discriminating the chemical form of 14C species in gaseous waste from nuclear facilities. The system consists of an air sample reservoir, a concentration apparatus, a radio-gas chromatograph, and microcomputers. An air sample, which is part of the gaseous effluent released from a stack of a facility, is automatically collected in the tank by trigger signals of stack monitors. After passing the air through a silica gel column, carbon species contained in it are recovered in an activated carbon-supported palladium trap held at -120 degrees C. The recovered species are swept with helium gas and analyzed by the radiogas chromatograph using an activated carbon column and gas-flow counters. Output signals of the gas-flow counters are continuously recorded by the microcomputer. By using this system, the chemical forms of 14C, such as CO, CO2, CH4, C2H4, C2H6, and C3H8 are identified and quantified. A detectable concentration of 0.3 mBq cm-3 for 14CO2 can be obtained. The system has been used to monitor the gaseous waste released from the radioisotope production laboratory and the Japan Research Reactor 2 at Japan Atomic Energy Research Institute. PMID- 1597383 TI - Risk estimation of radioactive contamination after the Chernobyl accident using bioindicators. AB - After the Chernobyl nuclear accident, game meat and, in particular, sheep meat in the Republic of Croatia showed a high degree of radioactive contamination compared to large livestock. The activity concentrations of 131I, 134Cs, and 137Cs were measured in meat and internal organs (i.e., lung, liver, kidney, and heart) of game (e.g., venison, hare, and wild boar) and sheep that were used as biological indicators of radioactive contamination. In order to estimate the importance of game and sheep as a dietary source of radioactivity, the effective dose equivalent for the average and critical population (hunters and livestock raising families) were calculated. The data indicated that sheep meat represents greater risk for the human population, in case of a nuclear accident, than game meat. The share of meat from sheep (4.4%) prevailed over the share of meat from game (0.5%) when comparing the average intake of meat per inhabitant in Croatia. This result pointed to an increased risk for families who depend mostly on sheep meat in the case of a nuclear accident. PMID- 1597384 TI - Guidelines for health physics program content: baccalaureate level. AB - Guidelines are suggested for baccalaureate health physics program content based on the schema used in a prior publication. The Guidelines assume a program with a primary emphasis on generalized health physics and presuppose an institutional breadth coursework requirement. Methods of strengthening areas of current general weakness are proposed, and one version of a coursework model is presented. Comments to the author and the Manpower and Professional Education Committee of the Health Physics Society are welcomed. PMID- 1597386 TI - Dosimetry calculations for concentric cylindrical source and target regions with application to blood vessels. AB - Geometry factors are derived for source and target regions consisting of concentric circular cylinders and cylindrical shells. Line-source kernels are derived from point kernels for monoenergetic electrons and photons. The geometry factors and line-source kernels are then combined to yield electron and photon absorbed fractions that, in turn, are used to calculate conversion factors for dose rates in blood vessel walls from radionuclides in the blood. Example calculations are presented for selected radionuclides and for blood vessels of three representative sizes. PMID- 1597385 TI - Dosimetric properties of europium-doped potassium bromide thermoluminescent crystals. AB - The dosimetric thermoluminescent properties of potassium bromide crystals doped with europium have been investigated. Nominal concentrations of europium ions varied between 0.01% and 1%. The crystals were annealed prior to irradiation following different thermal treatments. We report the glow curve and dose response characteristics to 60Co gamma rays. After a particular annealing, the crystals showed a strong thermoluminescent peak near 100 degrees C and a linear response for doses between 0.03 cGy and 10 cGy. The sensitivity is approximately 10 times that of lithium fluoride (TLD-100). PMID- 1597387 TI - Spatial and temporal indoor radon variations. AB - This paper examines the ability of standard radon measurement protocols to predict long-term radon concentrations in houses located in the upper Midwest. It was observed that: (1) significant radon variations can occur on a spatial scale as small as a single floor; (2) radon measurements that integrate for periods less than 3 mo are reliable only to within a factor of 2 or more; and (3) contemporary, short-term measurements within existing structures may not accurately reflect past radon concentrations. Two-hundred forty-three occupied houses located in 40 towns were monitored for at least 1 y using alpha-track detectors. If lifetime radon exposure estimates need to be determined accurately, then long-term, integrating radon detectors should be placed in several rooms of each house. In radon atmospheres that may not be stable for long periods of time, it is suggested that multiple, year-long measurements or surface alpha activity measurements in combination with year-long alpha-track measurements are needed for an accurate lifetime radon assessment. PMID- 1597388 TI - 222Rn detection efficiency and sensitivity coefficient of the LR 115-II nuclear track detector. AB - Radon activity concentrations in air were measured by the Kodak-Pathe LR 115-II nuclear track detector. Using the calibrated sensitivity coefficient of the detector (k = 0.0285 Bq-1 m3 tr cm-2 d-1 = 0.33 cm), the critical detection angle was calculated. In the alpha-particle energy region of 1-3.7 MeV, the detector efficiency for 241Am was near 32% but the 222Rn detector efficiency was 23%. The permeability constant of the detector paper filter was measured in a standard radon atmosphere and a value of 9.08 x 10(-6) cm2 s-1 was obtained. PMID- 1597389 TI - Photoneutron production in the primary barriers of medical accelerator rooms. AB - Several radiation surveys, at medical linear accelerator facilities where lead or steel had been used with concrete to fabricate the primary barriers, revealed the existence of a sizable neutron field outside the shielding. This neutron field is produced by photoneutrons generated in the metal portion of the shield when the primary x-ray beam is aimed at the barrier. A method was developed to calculate the neutron dose-equivalent rate expected outside a primary shield when it is irradiated by a high-energy x-ray beam. It was found that the minimum photoneutron dose was produced when the metal part of the shield was positioned inside the treatment room in front of the concrete and also by using steel in place of lead. A thickness of less than or equal to 17 cm of metal on the inner surface of the shield produced only a slight increase in the neutron dose equivalent outside the barrier. PMID- 1597391 TI - The pathology of Deadly Deceit. PMID- 1597390 TI - An evaluation of radiation and dust hazards at a mineral sand processing plant. PMID- 1597392 TI - [Study trip to Svalbard]. PMID- 1597393 TI - Sex hormone-binding globulin. Binding to cell membranes and generation of a second messenger. PMID- 1597394 TI - The free hormone hypothesis. Distinction from the free hormone transport hypothesis. AB - I. The free hormone transport hypothesis: distinction from the free hormone hypothesis. II. The free hormone hypothesis: importance of the rate-limiting step in tissue uptake. III. Explicit consideration of multiple plasma hormone-binding proteins in transport models. IV. Diffusion barriers in transport models. V. Functions of plasma hormone-binding proteins. VI. Conclusions and areas for future investigation. PMID- 1597395 TI - Testicular function in hyperthyroidism. AB - Testicular function was assessed in nine men aged 17 to 35 years and seven men aged 36 to 46 years with Graves' disease. Levels of total testosterone, estradiol, sex hormone binding globulin, luteinizing hormone, and follicle stimulating hormone, and gonadotropin responses to gonadotropin releasing hormone were significantly greater than these levels and responses in age-matched controls. Although the percentage of free testosterone was lower than control values in the hyperthyroid men, calculated levels of free testosterone were not different from normal. Lower than normal percentages of free estradiol values resulted in higher than normal calculated free estradiol levels. As a result, the free testosterone/free estradiol ratio in the men with Graves' disease was lower than normal. Although mean sperm densities in the hyperthyroid men were not different from control values, the percent forward progressive motility of sperm from these men was significantly lower than control values. The hormonal and seminal abnormalities corrected when the patients became euthyroid after radioiodine therapy. The results of this study indicate that hyperthyroid men may have abnormalities in their hypothalamic-pituitary-testicular axes. PMID- 1597396 TI - Effects of insulin-like growth factor-I on androgen production by highly purified pubertal and adult rat Leydig cells. AB - Leydig cells were isolated and purified from adult and midpubertal rats to study the effects of insulin-like growth factor-I (IGF-I) on steroidogenesis. Androgen production, as measured in Leydig cell conditioned culture media, from four different treatment groups (1 = no hormone; 2 = 70 ng/ml IGF-I; 3 = 0.1 ng/ml LH; 4 = 70 ng/ml IGF-I + 0.1 ng/ml LH) were compared daily. After 3 days in culture, the cells were treated with a maximally stimulating dose of luteinizing hormone (LH) (100 ng/ml) for 3 hours. Androgen production was highest in the cells treated with both IGF-I and low concentrations of LH. In the presence of IGF-I, regardless of LH, cells derived from pubertal animals had a greater increase in steroidogenesis during the culture period than did cells from adult animals. Pretreatment with IGF-I prior to maximal LH stimulation induced a greater increase in androgen production in cells from pubertal rats than in cells from adult animals. It is concluded that IGF-I has a direct effect on Leydig cells and may act synergistically with LH to promote androgen synthesis. The greater response in pubertal cells raises the possibility that IGF-I is important in the maturing process of the testis. PMID- 1597398 TI - New measures of sperm motion. I. Adaptive smoothing and harmonic analysis. AB - Several kinematic measures from computer-aided sperm analysis (CASA) instruments depend critically upon the computation of the spatially averaged path of a sperm's curvilinear swimming trajectory. Presently available instruments compute the average path by smoothing the curvilinear trajectory using a fixed-length running average. We demonstrate that this method significantly distorts the spatially averaged path for irregularly swimming sperm, both within and between trajectories, resulting in inaccurate calculations for the velocity of the average path (VAP), amplitude of lateral head displacement (ALH), beat-cross frequency (BCF), wobble of the curvilinear trajectory (WOB), and straightness of the curvilinear trajectory (STR). The authors introduce an alternative approach, based on engineering signal processing techniques, where the width of the running average is adapted to the changing wavelengths of the major spatial oscillations of each curvilinear trajectory. How this adaptive method results in less distortion of the average path and produces more accurate characterizations of the above measures is shown. This method is implemented in a computer program developed by the authors, called PathTool. It is also demonstrated that the simple methods used to characterize the frequency and amplitude of the major oscillation in a sperm's curvilinear trajectory (ie, BCF and ALH) are only accurate for the most periodic, progressive, and symmetrical trajectories. Three new measures are introduced, based on mathematical harmonic analysis, that are more robust alternatives to the present methods. These new methods and measures are initially evaluated using prototypical sperm trajectories from human semen. Results suggest that adaptive smoothing and harmonic analysis produce more accurate estimates of the frequency and magnitude of oscillations in sperm trajectories than the method based on fixed-length smoothing, BCF, and ALH. PMID- 1597397 TI - A comparison of critical osmolality and hydraulic conductivity and its activation energy in fowl and bull spermatozoa. AB - Measurements were made of critical osmolality, the osmolality at which 50% of the cells are lysed, and of the permeation time, the time taken to lyse 50% of the cells in an osmotic solution lower than the critical osmolality, for fowl and bull spermatozoa. Cell lysis was determined by means of fluorescent viability stains (carboxyfluorescein diacetate and propidium iodide) using a flow cytometer. The advantages and pitfalls of this approach are addressed. The values obtained have been used to compute the water permeability, or hydraulic conductivity, of the plasma membrane and its activation energy for each species. Fowl spermatozoa were found to have a lower critical osmolality (17 mOsm) than bull spermatozoa (36 mOsm), and this is discussed in relation to the differences in cell shape and size. The hydraulic conductivities of fowl and bull spermatozoa were 2.1 and 10.8 microns x atmosphere x minute, respectively, and the respective activation energies were 4.4 and 3.0 kcal/mol. The relevance of these findings to cryopreservation of spermatozoa is considered. PMID- 1597399 TI - GnRH-A induced arrest of spermiogenesis in rats is associated with altered androgen binding protein distribution in the testis and epididymis. AB - This study examines the effects of a potent gonadotropin releasing hormone (GnRH) antagonist (GnRH-A, Ac-D[2] Nal1, 4-CL-D Phe2, D-Trp3, D-Arg6, D-Ala10) upon the distribution of androgen binding protein (ABP) in serum, testis, and epididymis, and its relationship with the completion of spermatogenesis in Sprague-Dawley rats. After 2 weeks of daily injections of 10 micrograms/kg, 50 micrograms/kg, 100 micrograms/kg, or 500 micrograms/kg of GnRH-A, testicular ABP content was either unchanged or elevated (P less than 0.05), and serum ABP levels were elevated (P less than 0.01). Spermatogenesis was maintained in animals administered 10 micrograms/kg or 50 micrograms/kg GnRH-A, and epididymal ABP content remained unchanged. On the other hand, daily injections of 100 micrograms/kg or 500 micrograms/kg GnRH-A resulted in a significant decrease in epididymal ABP content (P less than 0.05), and spermatogenesis was arrested at early spermiogenesis. After 4 weeks of GnRH-A administration, both testicular and epididymal ABP were decreased in a dose-dependent manner in animals receiving doses of 50 micrograms/kg or higher of GnRH-A. In order to evaluate the normalcy of the bidirectional release of ABP in GnRH-A treated rats, additional rats were given daily injections of 25 micrograms/kg or 250 micrograms/kg of GnRH-A for 2 weeks. Concentrations of ABP in interstitial fluid (ITF) and seminiferous tubular fluid (STF) remained unchanged, but serum ABP levels were significantly increased (P less than 0.05) in rats administered 25 micrograms/kg GnRH-A. Qualitatively normal spermatogenesis was maintained and epididymal ABP content did not differ from that of control animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597400 TI - Sertoli cell plasma membrane polypeptides involved in spermatogenic cell-Sertoli cell adhesion. AB - This study concerns Sertoli cell-spermatogenic cell adhesive interactions in the seminiferous tubule. Sertoli cell surface polypeptides involved in germ cell Sertoli cell adhesion were identified by serological inhibition of an in vitro Sertoli-germ cell adhesion assay. This assay was modified from a previously reported adhesion assay, and employs a scanning laser cytometer for quantification of adherent cells. Reactivity of the polyclonal antiserum raised against rat Sertoli cells was also assessed via immunofluorescent microscopy. The addition of antiserum to the adhesion assay resulted in a 42% to 66% inhibition of cell-cell adhesion. Moreover, preincubation of antiserum with Sertoli cell monolayers resulted in a significant reduction of spermatogenic cell binding. Conversely, preincubation of antiserum with germ cells resulted in no reduction. Western blot analysis of the antiserum against purified Sertoli cell membranes indicated reactivity with four polypeptides. The data suggest that one or more of these polypeptides are directly involved in the adhesion of germ cells to Sertoli cell monolayers in vitro. PMID- 1597401 TI - Targeting antibodies to live tumor tissue in 3-D histoculture. PMID- 1597402 TI - Cytotoxicity of carbobenzoxy-protected amino acids. PMID- 1597403 TI - Proliferation of shark leukocytes. PMID- 1597404 TI - Effects of butyrate homologues on metallothionein induction in rat primary hepatocyte cultures. AB - Sodium butyrate (NaB), a 4-carbon fatty acid, has been reported to activate the metallothionein (MT) gene in certain carcinoma cell lines. Because the effects of NaB are dependent on the cell type investigated, this study was conducted to determine if NaB and its homologues induce MT in rat primary hepatocyte cultures. Hepatocytes were grown on monolayer for 12 h and subsequently treated with formate, acetate, propionate (NaP), NaB, and valeric acid for 10 to 58 h. To examine their interaction with known MT inducers, cadmium (Cd), zinc (Zn), or dexamethasone (Dex) were added to some cultures. MT protein in the cells was quantitated by the Cd-hemoglobin assay; MT-1 mRNA was analyzed by Northern blot hybridizations with oligonucleotide probes, and quantitated by slot-blot analysis. Among the 1 to 5 carbon carboxylic acids, only NaP (3 carbon) and NaB (4 carbon) induced MT. NaP and NaB alone produced a moderate increase in MT two- to fourfold over control), but when combined with Cd or Dex, an additive increase was observed. However, when combined with Zn, a synergistic increase was detected. NaB and Zn synergistically increased MT protein, but produced only an additive increase in MT mRNA, suggesting the involvement of some posttranscriptional event(s) in the NaB-Zn induction of MT. In conclusion, NaP and NaB induced MT in normal cultured rat hepatocytes, producing an additive increase in MT protein with Cd and Dex, and a synergistic increase in MT protein with Zn. PMID- 1597405 TI - Characterization of murine cell lines from diethylstilbestrol-induced uterine endometrial adenocarcinomas. AB - Neonatal treatment with estrogens is associated with development of uterine adenocarcinomas in CD-1 mice. Treatment with the synthetic estrogen diethylstilbestrol (DES) on Days 1 to 5 after birth results in 90% incidence of these hormone-dependent lesions in 18-mo.-old mice. Three cell lines were established from these DES-associated tumors. Each of these cell lines exhibited morphologic and ultrastructural characteristics of transformed epithelial cells, including an increased nuclear:cytoplasmic ratio, enlarged and irregular nuclei with multiple nucleoli and areas of chromatin condensation, positive staining for cytokeratin, desmosomes, and microvilli. After subcutaneous injection into nude mice, all three cell lines formed solid tumors within 4 wk. Although the primary uterine tumors and tumor transplants in nude mice had been shown to be estrogen dependent and estrogen-receptor positive, neither the monolayer growth nor the tumorigenicity of any of the three cell lines in this study was enhanced by or dependent on estrogen. Estrogen receptor levels were low in early and intermediate passage cells. Allele-specific oligonucleotide hybridization analysis of PCR-amplified cell line DNA revealed no point mutations in the 12th, 13th, or 61st codons of the K-ras or H-ras protooncogenes. Southern analysis revealed no changes in genomic organization of the putative tumor suppressor gene DCC, but demonstrated a three- to four-fold amplification of the c-myc gene in one cell line. Expression of c-myc RNA was concomitantly increased in the same cell line. These three transformed cell lines represent the end point in the process of hormone-associated tumorigenesis and as such should prove useful in investigating the molecular changes and the mechanisms involved in hormonal carcinogenesis. PMID- 1597406 TI - Ultrastructural and autoradiographic study of preimplantation rabbit embryos grown in conventional or uterine flushing-supplemented culture media. AB - Rabbit morulae and blastocysts were cultured in conventional culture media [Ham's F10 or BSM II supplemented with bovine serum albumin (BSA) or serum] or in Ham's medium supplemented with synchronous or asynchronous uterine flushings, mostly for 2 days, and afterwards investigated by light and electron microscopy and by autoradiography. Ultrastructure and cell proliferation differed considerably between cultured embryos and noncultured controls. Cultured embryos displayed more dead cells. They were developmentally retarded (predominance of smooth endoplasmic reticulum rather than the age-specific rough endoplasmic reticulum, mitochondria still round to ovoid shaped) and showed nonspecific signs of cells damage (swollen mitochondria and Golgi complex vesicles, increased number of lysosomes). All these features were also present in embryos grown in uterine flushing-supplemented media, but were less pronounced. Cell damage and impaired cell proliferation had affected trophoblast cells more than embryoblast cells. Endoderm could be differentiated only if culture had been started with blastocysts--not with morulae--and seems to require uterine secretions. No significant ultrastructural differences were observed between embryos cultured in synchronous or in asynchronous uterine flushings. Present results indicate that cultured preimplantation rabbit embryos deviate clearly from those grown in vivo and maintain, for some time, a better cellular structure--and probably function- in the presence of uterine flushings than in conventional culture media. Specific abnormal morphologic features related to a particular medium could not be identified. PMID- 1597407 TI - Chondrogenesis and myogenesis in micromass cultures of mesenchyme from mouse facial primordia. AB - The face develops from small buds of tissue positioned around the primitive mouth. The chondrogenic and myogenic cell populations contained within these facial primordia in mouse embryos have been investigated in short-term micromass culture. Chondrogenesis occurred in frontonasal mass mesenchyme from E11-E13 embryos, in maxillary mesenchyme from E12.5 embryos and was absent in mandibular mesenchyme. Myogenesis was greatest in mandibular mesenchyme, moderate in maxillary mesenchyme and low in the frontonasal mass. When compared with chick embryos the mouse facial primordia have lower chondrogenic potential, which in the case of the frontonasal mass may be related to the relative outgrowth of the primordia in the two species. Chondrogenesis in the mouse mandibular mesenchyme may be affected by the presence of a large population of odontogenic mesenchyme. The behavior of myogenic cell populations is related to the pattern of the musculature of the face, as the mandible contains the most muscle, the maxilla some, and the frontonasal mass none. However, the presence of myoblasts in early mesenchyme of all primordia may indicate that, as with chick, facial primordia are initially seeded with muscle cells and that the size of the cell population is subsequently controlled according to the development of the musculature within the primordia. PMID- 1597408 TI - The sigma 70 family: sequence conservation and evolutionary relationships. PMID- 1597409 TI - Purification and characterization of a novel enoyl coenzyme A reductase from Streptomyces collinus. AB - A novel NADPH-dependent enoyl reductase, catalyzing the conversion of 1 cyclohexenylcarbonyl coenzyme A (1-cyclohexenylcarbonyl-CoA) to cyclohexylcarbonyl-CoA, was purified to homogeneity from Streptomyces collinus. This enzyme, a dimer with subunits of identical M(r) (36,000), exhibits a Km of 1.5 +/- 0.3 microM for NADPH and 25 +/- 3 microM for 1-cyclohexenylcarbonyl-CoA. It has a pH optimum of 7.5, is most active at 30 degrees C, and is inhibited by both divalent cations and thiol reagents. Two internal peptide sequences were obtained. Ansatrienin A (an antibiotic produced by S. collinus) contains a cyclohexanecarboxylic acid moiety, and it is suggested that the 1 cyclohexenylcarbonyl-CoA reductase described herein catalyzes the final reductive step in the conversion of shikimic acid into this moiety. PMID- 1597410 TI - Identification of the promoter region of the Escherichia coli major cold shock gene, cspA. AB - The major cold shock protein of Escherichia coli, CS7.4, is produced at a level of 13% of total protein synthesis upon a temperature shift from 37 to 10 degrees C. The transcription of its gene (cspA) was found to be tightly regulated and induced only at low temperature. In addition, the cspA mRNA was extremely unstable at 37 degrees C, so that CS7.4 production was hardly detected when the culture temperature was shifted from 15 degrees C to 37 degrees C. The transcription initiation site (+1) was identified. In vivo footprinting demonstrated that the region from bases -35 to -73 was protected from chemical modification, and gel mobility shift analysis showed that a cold-shocked cell extract contained a factor(s) specifically bound to the fragment containing the sequence between bases -63 and -92. This factor was synthesized de novo only at low temperature, and its synthesis was inhibited by chloramphenicol. Possible functions of this factor are discussed. PMID- 1597411 TI - Regulation of nitrogenase-2 in Azotobacter vinelandii by ammonium, molybdenum, and vanadium. AB - Under diazotrophic conditions in the absence of molybdenum and in the presence of vanadium, Azotobacter vinelandii reduces N2 to NH4+ by using nitrogenase-2, a V containing enzyme complex encoded by vnfH (the gene for dinitrogenase reductase 2), and vnfDGK (the genes for dinitrogenase-2 subunits). Accumulation of the vnfHorfFd and vnfDGK transcripts occurred under Mo-deficient conditions in the presence and absence of V; however, in the case of vnfDGK, the protein products only accumulated in the presence of V. This suggests that V is required for translation of the vnfDGK transcripts. In addition, expression of vnfH-lacZ and vnfD-lacZ transcriptional fusions was only partially repressed in the presence of NH4+. Transcripts hybridizing with vnfH (1.4 and 1.0 kb), vnfDG (3.4 and 1.8 kb), and vnfK (3.4 kb) were detected in RNA extracted from wild-type cells cultured with NH4+ in the presence or absence of V. However, nitrogenase-2 subunits were not detected in extracts of cells derepressed for nitrogenase-2 in the presence of NH4+. These results indicate that this nitrogen source acts at the posttranscriptional level as well as at the transcriptional level. vnf transcripts were not detected in the presence of Mo (with or without NH4+). PMID- 1597412 TI - Role of divalent cations in the subunit associations of complex flagella from Rhizobium meliloti. AB - Rhizobium meliloti, a symbiotic, nitrogen-fixing soil bacterium with complex flagella, as well as other members of the family Rhizobiaceae, rapidly lost motility when suspended in buffers lacking divalent cations but retained good motility in buffers containing calcium, magnesium, barium, or strontium. Loss of motility was associated with loss of flagella from the cells. Analysis of flagella by sedimentation, gel electrophoresis, and electron microscopy revealed that removal of divalent cations from the complex flagella of R. meliloti resulted in extensive dissociation of the flagellar filaments into low-molecular weight subunits. Accordingly, divalent cations such as calcium and magnesium that are normally present at high concentrations in the soil solution may be crucial to the assembly and rigidity of complex flagella. PMID- 1597414 TI - Characterization of cytochromes from Methanosarcina strain Gol and their involvement in electron transport during growth on methanol. AB - Methanosarcina strain Go1 was tested for the presence of cytochromes. Low temperature spectroscopy, hemochrome derivative spectroscopy, and redox titration revealed the presence of two b-type (b559 and b564) and two c-type (c547 and c552) cytochromes in membranes from Methanosarcina strain Go1. The midpoint potentials determined were Em,7 = -135 +/- 5 and -240 +/- 11 mV (b-type cytochromes) and Em,7 = -140 +/- 10 and -230 +/- 10 mV (c-type cytochromes). The protoheme IX and the heme c contents were 0.21 to 0.24 and 0.09 to 0.28 mumol/g of membrane protein, respectively. No cytochromes were detectable in the cytoplasmic fraction. Of various electron donors and acceptors tested, only the reduced form of coenzyme F420 (coenzyme F420H2) and the heterodisulfide of coenzyme M and 7-mercaptoheptanoylthreonine phosphate (CoM-S-S-HTP) were capable of reducing and oxidizing the cytochromes at a high rate, respectively. Addition of CoM-S-S-HTP to reduced cytochromes and subsequent low-temperature spectroscopy revealed the oxidation of cytochrome b564. On the basis of these results, we suggest that one or several cytochromes participate in the coenzyme F420H2 dependent reduction of the heterodisulfide. PMID- 1597413 TI - Function of a relaxed-like state following temperature downshifts in Escherichia coli. AB - Temperature downshifts of Escherichia coli throughout its growth range resulted in transient growth inhibition and a cold shock response consisting of transient induction of several proteins, repression of heat shock proteins, and, despite the growth lag, continued synthesis of proteins involved in transcription and translation. The paradoxical synthesis of the latter proteins, which are normally repressed when growth is arrested, was explored further. First, by means of a nutritional downshift, a natural stringent response was induced in wild-type cells immediately prior to a shift from 37 to 10 degrees C. These cells displayed decreased synthesis of transcriptional and translational proteins and decreased induction of cold shock proteins; also, adaptation for growth at 10 degrees C was delayed, even after restoration of the nutrient supplementation. Next, the contribution of guanosine 5'-triphosphate-3'-diphosphate and guanosine 5' diphosphate-3'-diphosphate, collectively abbreviated (p)ppGpp, to the alteration in cold shock response was studied with the aid of a mutant strain in which overproduction of these nucleotides can be artificially induced. Induction of (p)ppGpp synthesis immediately prior to shifting this strain from 37 to 10 degrees C produced results differing only in a few details from those described above for nutritional downshift of the wild-type strain. Finally, shifting a relA spoT mutant, which cannot synthesize (p)ppGpp, from 24 to 10 degrees C resulted in a greater induction of the cold shock proteins, increased synthesis of transcriptional and translational proteins, decreased synthesis of a major heat shock protein, and faster adaptation to growth than for the wild-type strain. Our results indicate that the previously reported decrease in the (p)ppGpp level following temperature downshift plays a physiological role in the regulation of gene expression and adaptation for growth at low temperature. PMID- 1597415 TI - The rcsB gene, a positive regulator of colanic acid biosynthesis in Escherichia coli, is also an activator of ftsZ expression. AB - Wild-type genes which, when overexpressed, are capable of restoring the growth deficiency of the division mutant ftsZ84 of Escherichia coli on L medium containing no added NaCl have been isolated. One of these genes is rcsB, a positive regulator of colanic acid biosynthesis. A direct relationship between rcsB expression and FtsZ activity was observed, suggesting that RcsB specifically increases transcription of ftsZ, thus accounting for the restoration of colony formation by ftsZ84 mutant cells. Analysis of the 5' upstream sequence of rcsB revealed, in addition to the sigma 54 promoter sequence previously reported, a presumptive sigma 70 promoter and LexA-binding site plus an upstream sequence that is found to be essential for the expression of rcsB on a plasmid. The absence of the sigma 54 factor does not have a negative effect on the transcription of rcsB. The RcsB protein is an activator of its own synthesis, particularly in the presence of NaCl. Evidence which suggests that RcsB can be phosphorylated by a presumably modified EnvZ or PhoM sensor protein leading to a suppression of the growth deficiency of ftsZ84 mutant cells and to an increase in colanic acid production was obtained. We also demonstrated that the level of colanic acid is reduced when the cells carry a multicopy rcsC plasmid, suggesting that the RcsC sensor has phosphatase activity. PMID- 1597416 TI - Mutational analysis of signal transduction by ArcB, a membrane sensor protein responsible for anaerobic repression of operons involved in the central aerobic pathways in Escherichia coli. AB - In Escherichia coli, the expression of a group of operons involved in aerobic metabolism is regulated by a two-component signal transduction system in which the arcB gene specifies the membrane sensor protein and the arcA gene specifies the cytoplasmic regulator protein. ArcB is a large protein belonging to a subclass of sensors that have both a transmitter domain (on the N-terminal side) and a receiver domain (on the C-terminal side). In this study, we explored the essential structural features of ArcB by using mutant analysis. The conserved His 292 in the transmitter domain is indispensable, indicating that this residue is the autophosphorylation site, as shown for other homologous sensor proteins. Compression of the range of respiratory control resulting from deletion of the receiver domain and the importance of the conserved Asp-533 and Asp-576 therein suggest that the domain has a kinetic regulatory role in ArcB. There is no evidence that the receiver domain enhances the specificity of signal transduction by ArcB. The defective phenotype of all arcB mutants was corrected by the presence of the wild-type gene. We also showed that the expression of the gene itself is not under respiratory regulation. PMID- 1597417 TI - Nucleotide sequences of Bacillus subtilis flagellar biosynthetic genes fliP and fliQ and identification of a novel flagellar gene, fliZ. AB - Three genes from the Bacillus subtilis major che-fla operon have been cloned and sequenced. Two of the genes encode proteins that are homologous to the Escherichia coli and Salmonella typhimurium flagellar biosynthetic proteins FliP and FliQ. The third gene, designated fliZ, encodes a 219-amino-acid protein with a predicted molecular mass of 24,872 Da. FliZ is not significantly homologous to any known proteins. Null mutants in fliP and fliZ do not have flagella; however, motility can be restored to the fliZ null mutant by expression of fliZ from a plasmid. FliZ has a conventional N-terminal signal sequence that does not direct secretion of the protein but appears to target the protein to the membrane. Two possible models of insertion of FliZ into the membrane are described. PMID- 1597418 TI - Molecular characterization and regulation of the rhizosphere-expressed genes rhiABCR that can influence nodulation by Rhizobium leguminosarum biovar viciae. AB - A group of four rhi (rhizosphere-expressed) genes from the symbiotic plasmid of Rhizobium leguminosarum biovar viciae has been characterized. Although mutation of the rhi genes does not normally affect nodulation, in the absence of the closely linked nodulation genes nodFEL, mutations in the rhi genes can influence the nodulation of the vetch Vicia hirsuta. The DNA sequence of the rhi gene region reveals four large open reading frames, three of them constituting an operon (rhiABC) transcribed convergently toward the fourth gene, rhiR. rhiABC are under the positive control of RhiR, the expression of which is repressed by flavonoids that normally induce nod gene expression. This repression, which requires the nodD gene product (the transcriptional activator of nod gene expression), may be due to a cis effect caused by a high level of NodD-dependent expression from the adjacent nodO promoter, which is transcribed divergently from rhiR. RhiR shows significant similarities to a subfamily of transcriptional regulators that includes the LuxR and UvrC-28K proteins. RhiA shows limited homology to a short domain of the lactose permease, LacY, close to a region thought to be involved in substrate binding. No strong homologies were found for the other rhi gene products. It appears that RhiA and RhiB are cytoplasmic, whereas RhiC is a periplasmic protein, since it has a typical N-terminal transit sequence and a rhiC-phoA protein fusion expresses alkaline phosphatase activity. The biochemical role of the rhi genes has not been established, but it appears that they may play a role in the plant-microbe interaction, possibly by allowing the bacteria to metabolize a plant-made metabolite. PMID- 1597419 TI - Biosynthesis of riboflavin: cloning, sequencing, and expression of the gene coding for 3,4-dihydroxy-2-butanone 4-phosphate synthase of Escherichia coli. AB - 3,4-Dihydroxy-2-butanone 4-phosphate is biosynthesized from ribulose 5-phosphate and serves as the biosynthetic precursor for the xylene ring of riboflavin. The gene coding for 3,4-dihydroxy-2-butanone 4-phosphate synthase of Escherichia coli has been cloned and sequenced. The gene codes for a protein of 217 amino acid residues with a calculated molecular mass of 23,349.6 Da. The enzyme was purified to near homogeneity from a recombinant E. coli strain and had a specific activity of 1,700 nmol mg-1 h-1. The N-terminal amino acid sequence and the amino acid composition of the protein were in agreement with the deduced sequence. The molecular mass as determined by ion spray mass spectrometry was 23,351 +/- 2 Da, which is in agreement with the predicted mass. The previously reported loci htrP, "luxH-like," and ribB at 66 min of the E. coli chromosome are all identical to the gene coding for 3,4-dihydroxy-2-butanone 4-phosphate synthase, but their role had not been hitherto determined. Sequence homology indicates that gene luxH of Vibrio harveyi and the central open reading frame of the Bacillus subtilis riboflavin operon code for 3,4-dihydroxy-2-butanone 4-phosphate synthase. PMID- 1597420 TI - Genetic dissection of DNA binding and luminescence gene activation by the Vibrio fischeri LuxR protein. AB - The Vibrio fischeri luminescence (lux) genes are regulated by the 250-amino-acid residue LuxR protein and a V. fischeri metabolite termed autoinducer. The V. fischeri lux regulon consists of two divergently transcribed units. Autoinducer and LuxR activate transcription of the luxICDABE operon and autoregulate the luxR transcriptional unit. LuxR proteins with C-terminal truncations of up to 40 amino acid residues coded by plasmids with luxR 3'-deletion mutations are functional in negative autoregulation as demonstrated by using a luxR::lacZ transcriptional fusion as a luxR promoter probe in Escherichia coli. The truncated LuxR proteins showed little or no ability to activate transcription of luxICDABE, as indicated by using luminescence as a sensitive indicator of promoter strength in E. coli. Besides having no detectable activity as positive regulators of luxICDABE, LuxR proteins with C-terminal truncations of more than 40 amino acid residues had reduced or no detectable activity as negative autoregulators. The results suggest that amino acid residues in LuxR prior to no. 211 are sufficient for lux DNA binding. Residues in the region of 211 to 250 constitute a C-terminal tail that appears to be involved in activation of luxICDABE transcription either by interacting physically with the transcription initiation complex or by affecting lux DNA in the vicinity of the promoter. PMID- 1597421 TI - Physical map of the genome of Rhodobacter capsulatus SB 1003. AB - A map of the chromosome of Rhodobacter capsulatus was constructed by overlapping the large restriction fragments generated by endonucleases AseI and XbaI. The analyses were done by hybridization of single fragments with the restriction fragments blotted from pulsed-field gels and by grouping cosmids of a genomic library of R. capsulatus into contigs, corresponding to the restriction fragments, and further overlapping of the contigs. A technical difficulty due to a repeated sequence made it necessary to use hybridization with cloned genes and prior knowledge of the genetic map in order to close the physical circle in a unique way. In all, 41 restriction sites were mapped on the 3.6-Mb circular genome and 22 genes were positioned at 26 loci of the map. Cosmid clones were grouped in about 80 subcontigs, forming two groups, one corresponding to the chromosome of R. capsulatus and the other corresponding to a 134-kb plasmid. cos site end labeling and partial digestion of cosmids were used to construct a high resolution EcoRV map of the 134-kb plasmid. The same method can be extended to the entire chromosome. The cosmid clones derived in this work can be used as a hybridization panel for the physical mapping of new genes as soon as they are cloned. PMID- 1597422 TI - Mutant enrichment of Schizosaccharomyces pombe by inositol-less death. AB - Enrichment procedures, such as those utilizing inositol-less death, have proven to be extremely powerful for increasing the efficiency of identification of spontaneous mutants in a variety of procaryotic and eucaryotic organisms. We characterized inositol-less death in several widely used strains of the inositol requiring yeast Schizosaccharomyces pombe and determined conditions under which this phenomenon can be used to enrich for mutants. Conflicting reports in the literature on the effects of inositol starvation upon viability of S. pombe had cast doubt on the suitability of using inositol-less death in a mutant enrichment procedure for this organism. We determined that inositol-less death was strain dependent, with differences in viability of up to 5 orders of magnitude observed between the most-sensitive strain, 972, and the least-sensitive strain, SP837. Inositol-less death was also dependent upon the cell concentration at the time of initiation of starvation. While inositol-less death occurred at all four temperatures tested, the kinetics of death was slower at 16 degrees C than at 23, 30, or 37 degrees C. Inositol-less death was observed during growth in fermentable and nonfermentable carbon sources, although loss of viability in glycerol-ethanol was significantly slower than that in glucose, sucrose, or raffinose. The feasibility of exploiting inositol-less death to enrich for spontaneous mutants was demonstrated by the identification of amino acid auxotrophs, nucleotide auxotrophs, carbon source utilization mutants, and temperature-sensitive mutants. By varying starvation conditions, some mutants were recovered at frequencies as high as 5.7 x 10(-2), orders of magnitude higher than the spontaneous mutation rate. PMID- 1597423 TI - Attachment sites for bacteriophage P2 on the Escherichia coli chromosome: DNA sequences, localization on the physical map, and detection of a P2-like remnant in E. coli K-12 derivatives. AB - Integration of bacteriophage P2 into the Escherichia coli genome involves recombination between two attachment sites, attP and attB, one on the phage and one on the host genome, respectively. At least 10 different attB sites have been identified over the years. In E. coli C, one site, called locI, is preferred, being occupied before any of the others. In E. coli K-12, no such preference is seen (reviewed in L. E. Bertani and E. W. Six, p. 73-143, in R. Calendar, ed., The Bacteriophages, vol. 2, 1988). The DNA sequence of locI has been determined, and it shows a core sequence of 27 nucleotides identical to attP (A. Yu, L. E. Bertani, and E. Haggard-Ljungquist, Gene 80:1-12, 1989). By inverse polymerase chain reactions, the prophage-host junctions of DNA extracted from P2 lysogenic strains have been amplified, cloned, and sequenced. By combining the attL and attR sequences, the attB sequences of locations II, III, and H have been deduced. The core sequence of location II had 20 matches to the 27-nucleotide core sequence of attP; the sequences of locations III and H had 17 matches. Thus, the P2 integrase accepts at least up to 37% mismatches within the core sequence. The E. coli K-12 strains examined all contain a 639-nucleotide-long cryptic remnant of P2 at a site with a sequence similar to that of locI but that may have a different map position. The P2 remnant consists of the C-terminal part of gene D, all of gene ogr, and attR. Locations II, III, and H have been located on Kohara's physical map to positions 3670, 1570 to 1575, and 2085, respectively. PMID- 1597424 TI - Escherichia coli K-12 and B contain functional bacteriophage P2 ogr genes. AB - The bacteriophage P2 ogr gene encodes an essential 72-amino-acid protein which acts as a positive regulator of P2 late transcription. A P2 ogr deletion phage, which depends on the supply of Ogr protein in trans for lytic growth on Escherichia coli C, has previously been constructed. E. coli B and K-12 were found to support the growth of the ogr-defective P2 phage because of the presence of functional ogr genes located in cryptic P2-like prophages in these strains. The cryptic ogr genes were cloned and sequenced. Compared with the P2 wild-type ogr gene, the ogr genes in the B and K-12 strains are conserved, containing mostly silent base substitutions. One of the base substitutions in the K-12 ogr gene results in replacement of an alanine with valine at position 57 in the Ogr protein but does not seem to affect the function of Ogr as a transcriptional activator. The cryptic ogr genes are constitutively transcribed, apparently at a higher level than the wild-type ogr gene in a P2 lysogen. PMID- 1597425 TI - Molecular genetics of the flgI region and its role in flagellum biosynthesis in Caulobacter crescentus. AB - The differentiating bacterium Caulobacter crescentus has been studied extensively to understand how a relatively simple life form can govern the timing of expression of genes needed for the production of stage-specific structures. In this study, a clone containing the 5.3-kb flaP region was shown to contain the flgI, cheL, and flbY genes arranged in an operon with transcription proceeding from flgI to flbY. The predicted flgI polypeptide shows remarkable identity (44%) to the flagellar basal body P-ring protein encoded by the flgI gene of Salmonella typhimurium. flgI mutations case a reduction in the levels of flagellin production and the overproduction of the hook proteins. Therefore, the flgI encoded P-ring protein is required for normal flagellin and hook protein synthesis, suggesting that basal body assembly may play a role in the regulation of flagellar gene expression. The flbY gene probably is a basal body component as well, since flbY mutants have flagellin and hook protein synthesis patterns similar to those exhibited by other basal body mutants. The smaller cheL gene complements a mutant that is unable to respond to chemotactic signals despite possessing a functional flagellum. This is the first example of an operon containing both flagellar and chemotaxis genes in C. crescentus. PMID- 1597426 TI - Analysis of mutations in trfA, the replication initiation gene of the broad-host range plasmid RK2. AB - Plasmids with mutations in trfA, the gene encoding the replication initiation protein of the broad-host-range plasmid RK2, were isolated and characterized. Mutants identified from a nitrosoguanidine bank were defective in supporting the replication of a wild-type RK2 origin in Escherichia coli. Most of the mutations were clustered in a region of trfA corresponding to the carboxy-terminal quarter of the TrfA protein. 5' and 3' deletion mutants of trfA were also constructed. A C-terminal deletion of three amino acids of the Tr A protein was completely nonfunctional for RK2 replication. However, a deletion of 25 amino acids from the start of the 33-kDa TrfA protein was still competent for replication. Further characterization of the point and deletion trfA mutants in vivo revealed that a subset was capable of supporting RK2 replication in other gram-negative bacteria, including Pseudomonas putida, Agrobacterium tumefaciens, and Azotobacter vinelandii. Selected mutant TrfA proteins were partially purified and characterized in vitro. Velocity sedimentation analysis of these partially purified TrfA proteins indicated that the wild-type protein and all mutant TrfA proteins examined exist as dimers in solution. Results from in vitro replication assays corroborated the experimental findings in vivo. Gel retardation results clearly indicated that the point mutant TrfA-33:151S, which was completely defective in replication of an RK2 origin in all of the bacterial hosts tested in vivo, and a carboxy-terminal deletion mutant, TrfA-33:C delta 305, were not able to bind iterons in vitro. In addition to the partially defective or could not be distinguished from the wild-type protein in binding to the origin region. The mutant proteins with apparently normal DNA-binding activity in vitro either were inactive in all four gram-negative bacteria tested or exhibited differences in functionality depending on the host organism. These mutant TrfA proteins may be altered in the ability to interact with the replication proteins of the specific host bacterium. PMID- 1597427 TI - Mutational analysis of the Rhizobium meliloti nifA promoter. AB - The nifA gene of Rhizobium meliloti, the bacterial endosymbiont of alfalfa, is a regulatory nitrogen fixation gene required for the induction of several key nif and fix genes. Transcription of nifA is strongly induced in planta and under microaerobic conditions ex planta. Induction of nifA, in turn, is positively controlled by the fixL and fixJ genes of R. meliloti, the sensor and regulator, respectively, of a two-component system responsible for oxygen sensing by this bacterium. This system is also responsible for the positive induction of fixK. Here, we report that chemical and oligonucleotide site-directed mutageneses of the nifA promoter (nifAp) were conducted to identify nucleotides essential for induction. Nineteen mutants, including 14 single-point mutants, were analyzed for microaerobic induction of nifAp in R. meliloti. Critical residues were identified in an upstream region between base pairs -54 and -39 relative to the transcription start site. Attempts at separating the upstream and downstream regions of the nifA promoter so as to maintain fixJ-dependent activity were unsuccessful. A 5' deletion of the fixK promoter (fixKp) to -67 indicates that sequences upstream of this position are not required for microaerobic induction. A sequence comparison of the -54 to -39 region of nifAp with the upstream sequences of fixKp does not reveal a block of identical nucleotides that could account for the fixJ-dependent microaerobic induction of both promoters. Many of the defective nifAp mutants in this region, however, are in residues with identity to fixKp in an alignment of the promoters according to their transcription start sites. Therefore, it is possible that there is a common sequence motif in the -54 to -39 region of the two promoters that is required for fixLJ-dependent microaerobic induction. PMID- 1597428 TI - Nucleotide sequence and characterization of four additional genes of the hydrogenase structural operon from Rhizobium leguminosarum bv. viciae. AB - The nucleotide sequence of a 2.5-kbp region following the hydrogenase structural genes (hupSL) in the H2 uptake gene cluster from Rhizobium leguminosarum bv. viciae UPM791 was determined. Four closely linked genes encoding peptides of 27.9 (hupC), 22.1 (hupD), 19.0 (hupE), and 10.4 (hupF) kDa were identified immediately downstream of hupL. Proteins with comparable apparent molecular weights were detected by heterologous expression of these genes in Escherichia coli. The six genes, hupS to hupF, are arranged as an operon, and by mutant complementation analysis, it was shown that genes hupSLCD are cotranscribed. A transcription start site preceded by the -12 to -24 consensus sequence characteristic of NtrA dependent promoters was identified upstream of hupS. On the basis of the lack of oxygen-dependent H2 uptake activity of a hupC::Tn5 mutant and on structural characteristics of the protein, we postulate that HupC is a b-type cytochrome involved in electron transfer from hydrogenase to oxygen. The product from hupE, which is needed for full hydrogenase activity, exhibited characteristics typical of a membrane protein. The features of HupC and HupE suggest that they form, together with the hydrogenase itself, a membrane-bound protein complex involved in hydrogen oxidation. PMID- 1597430 TI - Overproduction of DnaE protein (alpha subunit of DNA polymerase III) restores viability in a conditionally inviable Escherichia coli strain deficient in DNA polymerase I. AB - A polA12 recA718 double mutant of Escherichia coli, in which DNA polymerase I is temperature sensitive, was unable to maintain normal DNA synthesis or to form colonies on rich media at 42 degrees C. Overproduction of DnaE protein, the polymerizing alpha subunit of DNA polymerase III, restored bacterial DNA replication and cell viability, as well as the PolI-dependent replication of the plasmid carrying dnaE. PMID- 1597429 TI - Efficient production and processing of elastase and LasA by Pseudomonas aeruginosa require zinc and calcium ions. AB - The ability of Pseudomonas aeruginosa to degrade elastin, a major component of connective tissue, likely contributes to its pathogenicity and multiplication in human tissues. Two extracellular enzymes are required for P. aeruginosa elastolytic activity: elastase and LasA. Elastase is a zinc metalloprotease, but little is known about the structure of LasA. When grown under metal ion-deficient conditions, P. aeruginosa culture supernatants were found to exhibit a low level of elastolytic activity, which coincided with production of low levels of the 51 kDa proelastase and no detectable LasA. By using this fact to identify factors that promote elastolytic activity, P. aeruginosa PAO1, FRD2, and DG1 were grown in metal ion-deficient medium supplemented with zinc (10(-4) M ZnCl2), calcium (2.5 x 10(-3) M CaCl2), or iron (10(-4) M FeCl3). High levels of proteolytic and elastolytic activity were exhibited by all strains when cultured in the presence of both zinc and calcium, and this was associated with the production of mature 33-kDa elastase and 21-kDa LasA. Supplementing DG1 and PAO1 cultures with zinc alone stimulated the production of 33-kDa elastase, which, because of the calcium deficient conditions, exhibited low proteolytic and elastolytic activities. Zinc also stimulated the production of a 41-kDa form of LasA in DG1 and PAO1 culture supernatants. Elastase production by FRD2 cultured in the presence of zinc alone differed from that by the other two strains in that supernatants contained 33-kDa elastase, a 21-kDa form of LasA, and exhibited high proteolytic and elastolytic activities. Such strain-associated differences in LasA processing and elastase activity can be explained by differences in metal ion-scavenging mechanisms adapted by the strains. Supplementing cultures with calcium stimulated the production of elastase but had no effect on LasA production. The elastase produced exhibited variable sizes, possibly resulting from aberrant processing reactions, and showed little proteolytic activity. Proteolytic activity could be recovered from 33-kDa elastase produced in the presence of calcium by inclusion of zinc in the enzymatic assay. Although iron was previously found to exert a repressive effect on P. aeruginosa elastolytic activity, iron exerted little effect on elastolytic activity when added to cultures containing both zinc and calcium. These studies support the conclusion that elastase production and processing are promoted by both zinc and calcium. LasA production, in comparison, is stimulated by zinc, with both zinc and calcium facilitating its processing. The association of 41-kDa LasA with a low level of elastolytic activity and of 21 kDa LasA with a high level of activity supports the conclusion that lasA encodes a larger, precursor protein which is processed to an active 21-kDa form during secretion. PMID- 1597431 TI - Constitutive mutations of Agrobacterium tumefaciens transcriptional activator virG. AB - The virulence (vir) genes of Agrobacterium tumefaciens Ti plasmids are positively regulated by virG in conjunction with virA and plant-derived inducing molecules. A procedure that utilizes both genetic selection and a genetic screen was developed to isolate mutations in virG that led to elevated levels of vir gene expression in the absence of virA and plant phenolic inducers. Mutants were isolated at a frequency of 1 in 10(7) to 10(8). Substitution mutations at two positions in the virG coding region were found to result in the desired phenotype. One mutant had an asparagine-to-aspartic acid substitution at residue 54, and the other contained an isoleucine-to-leucine substitution at residue 106. In both cases, the mutant phenotype required the presence of the active-site aspartic acid residue at position 52. Further analysis showed that no other substitution at residue 54 resulted in a constitutive phenotype. In contrast, several substitutions at residue 106 led to a constitutive phenotype. The possible roles of the residues at positions 54 and 106 in VirG function are discussed. PMID- 1597432 TI - Doublet translocation at GGA is mediated directly by mutant tRNA(2Gly). AB - Members of the sufS class of -1 frameshift suppressors have alterations of the GGA/G-decoding tRNA(2Gly). Suppressor-promoted frameshifting at GGA was shown in this study to be directly mediated by the mutant tRNA(2Gly). We disproved the possibility that, in the presence of the compromised mutant tRNA(2Gly), either wild-type tRNA(1Gly), wild-type tRNA(3Gly), a GGA-reading mutant form of tRNA(3Gly), or any other agent suppresses the frameshift mutation trpE91. PMID- 1597435 TI - Mitochondrial DNA is not fragmented during apoptosis. AB - We have exposed mouse thymocytes and P-815 mastocytoma cells to four different conditions reported to cause apoptosis: 1) incubation in the absence of mitogenic factors; 2) incubation in the presence of dexamethasone; 3) stimulation with external ATP; 4) treatment with high concentrations of the K+ ionophore valinomycin. These treatments caused DNA fragmentation to a varying extent in the two cell types. High stringency hybridization with a cDNA probe specific to a mitochondrial DNA sequence revealed that during apoptosis induced by lack of mitogenic factors, dexamethasone, or extracellular ATP, mitochondrial DNA was not fragmented. On the contrary, valinomycin caused extensive degradation of mitochondrial DNA. These results support the notion that DNA fragmentation during apoptosis is a specific nuclear event and suggest that other agents, such as valinomycin, may act less selectively. PMID- 1597433 TI - Glucose-induced regulatory defects in the Saccharomyces cerevisiae byp1 growth initiation mutant and identification of MIG1 as a partial suppressor. AB - Saccharomyces cerevisiae byp1-3 mutants displayed a long lag phase when shifted from a nonfermentable carbon source to a medium containing glucose. The byp1-3 mutation also caused several defects in regulatory phenomena which occur during the transition from the derepressed state to the repressed state. As opposed to wild-type cells, the addition of glucose to cells of the byp1-3 mutant grown on nonfermentable carbon sources did not induce a cyclic AMP signal. Fructose-2,6 bisphosphate formation and inactivation of fructose-1,6-bisphosphatase were severely delayed, but trehalase activation was not affected. In addition, the induction of pyruvate decarboxylase both at the level of activity and that of transcription was very slow compared with that in wild-type cells. These pleotropic defects in glucose-induced regulatory phenomena might be responsible for the very long lag phase of byp1-3 cells and the inability of ascospores to initiate growth after germination on glucose media. Screening of a yeast gene library for clones complementing the byp1-3 phenotype resulted in the isolation of a truncated form of the previously described zinc finger transcription repressor MIG1. The entire MIG1 gene and the truncated form suppressed even on a single-copy vector the growth initiation defect but not the regulatory abnormalities of the byp1-3 mutant. MIG1 is not allelic to byp1-3. PMID- 1597434 TI - Purification and some properties of sulfite:ferric ion oxidoreductase from Thiobacillus ferrooxidans. AB - Sulfite:ferric ion oxidoreductase in the plasma membrane of Thiobacillus ferrooxidans AP19-3 was purified to an electrophoretically homogeneous state. The enzyme had an apparent molecular weight of 650,000 and was composed of two subunits (M(rs), 61,000 and 59,000) as estimated by sodium sulfate-polyacrylamide gel electrophoresis. The Michaelis constants of sulfite:ferric ion oxidoreductase for Fe3+ and sulfite ions were 1.0 and 0.071 mM, respectively. Sulfite:ferric ion oxidoreductase suffered from end product inhibition by 1 mM Fe2+. PMID- 1597436 TI - A possible target protein for smg-25A/rab3A small GTP-binding protein. AB - The smg-25A/rab3A protein (smg p25A) is a small GTP-binding protein implicated in intracellular vesicle traffic, particularly in neurotransmitter release from the presynapse. In the present study, we attempted to identify a target protein in bovine brain crude membranes that might be interacted with the GTP-bound form of smg p25A. When the guanosine-5'-(3-O-thio)triphosphate (GTP gamma S)-bound form of radioiodinated smg p25A and the crude membrane fraction of bovine brain were incubated with a cross-linker, disuccinimidyl suberate, and the sample was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by autoradiography, one radioactive band with a M(r) of about 110,000 was detected. This radioactive band appeared to be composed of radioiodinated smg p25A and a molecule with a M(r) of about 86,000. This molecule, tentatively termed here smg p25A target, was extracted from the membranes by a detergent and highly purified by column chromatographies and sucrose density gradient ultracentrifugation. The purified smg p25A target was sensitive to heat boiling and tryptic digestion, indicating that smg p25A target is a protein molecule. The M(r) of the purified smg p25A target was estimated to be about 85,000-86,000 from SDS-PAGE and to be about 100,000 from the S value. The cross-linking of radioiodinated smg p25A with the purified smg p25A target was inhibited by the GTP gamma S-bound form of non-radioactive smg p25A with an IC50 of about 8 nM. The GDP-bound form of smg p25A was much less effective. Other small GTP-binding proteins, such as c-Ki-ras p21, rhoA p21, smg p21B, and rab11 p24 were ineffective. These results indicate that a protein with a M(r) of about 85,000 100,000 is a target for smg p25A. PMID- 1597437 TI - The relation of ligand binding to redox state in the hexa-heme nitrite reductase of Wolinella succinogenes. AB - Ligand binding reactions and the relation between redox state and ligand binding in the hexa-heme nitrite reductase of Wolinella succinogenes have been studied using laser flash photolysis. On a picosecond time scale, a rapid excursion was observed corresponding to the breaking and reforming of an iron histidine bond. With the CO derivative, a geminate reaction was observed with a rate of 3 ns-1. On a nanosecond time scale, no slower geminate reactions were observed. For the cyanide derivative, no geminate reactions were observed at either time scale. The second order reaction of CO with the enzyme had a time course consisting of two distinct components. This time course changed in form as the enzyme came to equilibrium with CO, and the slower rebinding component was replaced by a faster rebinding component. It is suggested that CO binding enhances reduction of a heme with an unusually low redox potential and opens the structure of the active site to allow a faster second order reaction of CO. The proportion of the geminate CO reaction was unchanged, consistent with changes relatively remote from the ligand binding site. The second order reactions of cyanide also showed that redox effects influence its rebinding reaction. Adding cyanide to the CO complex of nitrite reductase showed that the two ligands have distinct heme binding sites. PMID- 1597438 TI - High resolution studies of the Xenopus laevis ribosomal gene promoter in vivo and in vitro. AB - The first high resolution maps of the Xenopus laevis ribosomal promoter and its flanking regions (-179 to +14) have been created by assaying point mutants both in oocyte and in vitro. Within the promoter boundaries (-141(-145) to +3(+4)), domains analogous to the Core Promoter and "Upstream Control Element" (UCE) were clearly detected. The base pairs at -133, within the UCE, and -20, -10, -7, and +3, within the Core, were all shown to be especially important for promotion. Between the Core and UCE, two central promoter elements (CPEs) were also resolved. Surprisingly, these CPEs did not correspond to the highly conserved enhancer homology (approximately -70 to -110), but to CCCGGCC motifs immediately flanking it. Although xUBF was shown to be a limiting component for in vitro transcription, none of the point mutations was found to affect the interaction of this factor with the promoter. PMID- 1597439 TI - Thymidine and 3'-azido-3'-deoxythymidine metabolism in human peripheral blood lymphocytes and monocyte-derived macrophages. A study of both anabolic and catabolic pathways. AB - 3'-Azido-3'-deoxythymidine (AZT) is HIV-inhibitory in human macrophages, which is surprising in view of the low AZT phosphorylation reported in macrophage extracts. To elucidate the mechanism of AZT activation, we studied AZT anabolism as well as catabolism in human lymphocytes and macrophages, and compared it to that of thymidine. Thymidine kinase (TK)-specific activity in mitogen-stimulated lymphocytes was 15 times higher than in macrophages. However, the TK activity per cell was only 1.3 times higher, because of the large macrophage cell volume. Total cellular TK activity, but not specific activity, matched the level of intracellular AZT anabolism. The substrate specificity of TK in macrophages strongly suggests that mitochondrial TK2 was the enzyme phosphorylating thymidine and AZT in these cells, whereas it was cytosolic TK1 in stimulated lymphocytes. In vivo thymidine catabolism was extensive, forming thymine and dihydrothymine. In macrophages more than 95% of the added thymidine (0.5 microM) was degraded within 60 min. AZT, in contrast, was not catabolized, which explains the high AZT nucleotide accumulation, a process opposed only by AZTMP excretion. The lack of catabolism together with phosphorylation by TK2 clarifies how AZT can inhibit human immunodeficiency virus in macrophages. The fact that TK2 and not TK1 phosphorylates AZT in macrophages should have important implications for combination chemotherapy. PMID- 1597440 TI - Purification and identification of the heat-stable factor required for pregnenolone-binding protein activity. Evidence that the factor is adenosine 3',5'-diphosphate. AB - This paper presents data identifying adenosine 3',5'-diphosphate (3',5'-ADP) as the small heat-stable factor essential for the active steroid binding complex of the adrenocortical pregnenolone-binding protein (PBP). Factor activity obtained from the boiled supernatant of partially purified PBP was isolated by high performance liquid chromatography using weak anion-exchange and hydrophobic (C18) chromatography sequentially. The purified material retained characteristic factor activity and presented a UV spectrum identical to that for authentic 3',5'-ADP. Mass spectroscopic analysis of the isolated factor revealed an M-H ion of appropriate mass (m/z = 426) and a decomposition pattern for the M-H ion that was consistent with the structure of 3',5'-ADP. The studies presented here demonstrate that authentic 3',5'-ADP can categorically substitute for factor prepared from the soluble fraction of the guinea pig adrenal. Specifically, 3',5' ADP potentiated ligand binding of partially purified native PBP and restored binding capacity to alkaline phosphatase-inactivated PBP in a dose-dependent manner. As is the case for adrenocortical factor activity, these effects were negated by pretreating the 3',5'-ADP with calf intestinal alkaline phosphatase. Other nucleotides similarly tested, including ADP isomers, were ineffective as factor substitutes. The sulfated form of 3',5'-ADP (i.e. 3'-phosphoadenosine 5' phosphosulfate) demonstrated some potential for restoring binding capacity to phosphatase-inactivated PBP; however, this compound was clearly inhibitory rather than stimulatory for native PBP activity. Taken collectively, the data overwhelmingly demonstrate that 3',5'-ADP is in fact the molecule required by the PBP for high affinity steroid binding complex formation. It is not yet known whether 3',5'-ADP acts allosterically or contributes directly to the structure of the steroid binding site. PMID- 1597441 TI - Phosphatidic acid that accumulates in platelet-derived growth factor-stimulated Balb/c 3T3 cells is a potential mitogenic signal. AB - We developed a monoclonal antibody specific to phosphatidic acid (PA). Using this antibody, a novel method to quantify trace amounts of PA was achieved. With the method, PA can be measured in the range of 20-500 pmol. We applied this method to quantify changes in PA levels in Balb/c 3T3 cells stimulated by platelet-derived growth factor. PA contents were very low in quiescent cells and dramatically increased with time up to 15 min. On the other hand, a biphasic diacylglycerol (DG) increase was found. The early phase showed a transient small peak of DG at 30 s followed by a decrease to 1 min. In the second phase, DG accumulated gradually but very markedly up to 15 min. Treatment with propranolol, a PA phosphohydrolase inhibitor, enhanced the accumulation of PA and inhibited the formation of DG in the second phase. However, R59022, a DG kinase inhibitor, did not influence the accumulation of DG or PA, suggesting that platelet-derived growth factor stimulates mainly phospholipase D-catalyzed hydrolysis of phospholipids rather than phospholipase C-catalyzed hydrolysis in the second phase. PA, even after contaminating lyso-PA was removed, could stimulate DNA synthesis, although lyso-PA was 25 times more potent. Moreover, phospholipase D was found to be a much stronger mitogen than phospholipase C. Phospholipase D treatment caused a biphasic accumulation of PA. PA levels reached a maximum at 1 h, and then decreased between 1 and 2 h; finally, there was a gradual elevation up to 10 h. In this case, there was no significant DG accumulation. On the other hand, phospholipase C treatment induced only DG accumulation without any significant change in PA. These results indicate that PA accumulation, rather than an increase in DG, correlates well with mitogenesis. PMID- 1597442 TI - Plasmalopsychosine, a novel plasmal (fatty aldehyde) conjugate of psychosine with cyclic acetal linkage. Isolation and characterization from human brain white matter. AB - Through a systematic examination of basic (cationic) lipids separated on Folch's lower phase from extracts of human brain by cation exchange chromatography on carboxymethyl Sephadex in a chloroform/methanol mixture, followed by successive chromatographies on Florisil and Iatrobeads columns, five compounds of basic lipids were separated. Two major unknown compounds A and B and a minor unknown compound C were separated, in addition to minor compounds sphingosine and N,N dimethylsphingosine. This paper describes the isolation and chemical characterization of major unknown compounds A and B, which were found only in the white matter but not in the gray matter of the human brain. Unmodified psychosine (galactosylsphingosine) was essentially undetectable under the experimental conditions. Unknown compounds A and B were identified as novel plasmal (fatty aldehyde) conjugates of psychosine with cyclic acetal linkage at the galactosyl residue of psychosine. Fatty aldehydes were identified as mainly palmital (16:0) and stearal (18:0). Sphingosine was identified as d18:1 sphingosine. Faster migrating compound A had 3,4-cyclic acetal linkage, and slower migrating compound B had 4,6-cyclic acetal linkage (where m is 14 or 16 and n is 12) as shown below. [formula: see text] Preliminary studies showed that compounds A, B, and C had a weak inhibitory effect on protein kinase C (PKC) and had no cytotoxic effect. In contrast, psychosine displayed a strong cytotoxicity and inhibitory effect on PKC. Therefore, the process controlling the addition or deletion of plasmal cyclic linkage to psychosine could be a crucial step in regulation of PKC, src, or other kinases susceptible to psychosine. PMID- 1597443 TI - Insertion and folding of the amino-terminal amphiphilic signal sequences of the mannitol and glucitol permeases of Escherichia coli. AB - Peptides which correspond to the NH2-terminal 23 or 22 residues of the mannitol and glucitol permeases (enzymes IImtl and IIgut of the bacterial phosphotransferase system; mtl-23 and gut-22) and which are believed to function in envelope targeting were synthesized chemically, and their interactions with lipid model membranes were studied. Both wild-type peptides penetrated phospholipid monolayers up to high surface pressures, and partition constants of 8.0 x 10(4) M-1 and 4.2 x 10(4) M-1, respectively, were derived from the incorporation isotherms of mtl-23 and gut-22 with monolayers of 1-palmitoyl-2 oleoyl-3-sn-phosphatidylcholine at 32 mN/m or bilayers of the same lipid. The mtl 23 peptide was highly alpha-helical in trifluoroethanol, sodium dodecyl sulfate, lysolecithin, or vesicles of 1-palmitoyl-2-oleoyl-3-sn-phosphatidylglycerol, with estimated percentages of alpha-helix ranging between 60 and 85%. The interactions with model membranes of several single site mutants (S3P, D4P, and D4K) of mtl-23 which were defective in properly assembling the mannitol permease in the cytoplasmic membrane of Escherichia coli were also studied. The contents of alpha helix of these peptides in detergent micelles or phospholipid bilayers were not significantly changed compared with those of the wild type, suggesting that the amphiphilic NH2-terminal membrane-targeting domain could still be formed in these mutants. However, the mutants which contained a proline in positions 3 or 4, i.e. NH2-terminal to the proposed amphiphilic alpha-helix, partitioned into phospholipid monolayers with partition constants that were 2 or 4 times smaller than those of the wild type. Based on these data, a model of the amphiphilic structure of the NH2-terminal domain of the mannitol permease is discussed. This domain may interact physiologically with amphiphilic interfaces of lipids and/or proteins during membrane insertion. PMID- 1597444 TI - Mouse ornithine decarboxylase is stable in Trypanosoma brucei. AB - The cDNA encoding mouse ornithine decarboxylase (ODC) was incorporated into a transforming vector pTSA-NEO2 carrying a procyclic acidic repetitive protein promoter and a neomycin phosphotransferase gene. The plasmid thus constructed, pMOD300, was introduced into the procyclic forms of Trypanosoma brucei via electroporation, and the transformants, selected under G418, expressed an ODC activity 100 times above the background level. Contrary to the commonly observed short half-life of mouse ODC in mammalian cells, however, the mouse ODC activity expressed in T. brucei remained stable for at least 6 h when protein synthesis was inhibited by cycloheximide. Pulse labelings and chase experiments with the irreversible ODC inhibitor [3,4-3H]difluoromethylornithine followed by gel electrophoresis, or with L-[35S] methionine followed by immunoprecipitation and gel electrophoresis indicated that the stable mouse ODC expressed in T. brucei has the same subunit molecular weight as the native enzyme. By an in vitro assay of protein stability in rabbit reticulocyte lysates (Loetscher, P., Pratt, G., and Rechsteiner, M. (1991) J. Biol. Chem. 266, 11213-11220), the native mouse ODC and the enzyme expressed in T. brucei had the same degree of instability. Thus, the mouse ODC expressed in T. brucei is probably identical to the native mouse ODC. Its remarkable stability in T. brucei must be due to the absence in trypanosomes of the proteolytic machinery present in mammalian cells responsible for rapid degradation of mouse ODC. PMID- 1597445 TI - Antifolates induce inhibition of amido phosphoribosyltransferase in leukemia cells. AB - The pathway for de novo biosynthesis of purine nucleotides contains two one carbon transfer reactions catalyzed by glycinamide ribotide (GAR) and 5 aminoimidazole-4-carboxamide ribotide (AICAR) transformylases in which N10 formyltetrahydrofolate is the one-carbon donor. We have found that the antifolates methotrexate (MTX) and piritrexim (PTX) completely block the de novo purine pathway in mouse L1210 leukemia cells growing in culture but with only minor accumulations of GAR and AICAR to less than 5% of the polyphosphate derivatives of N-formylglycinamide ribotide (FGAR) which accumulate when the pathway is blocked completely by azaserine. This azaserine-induced accumulation of FGAR polyphosphates is completely abolished by MTX, indicating that inhibition of the pathway is at or before GAR transformylase (reaction 3; Lyons, S. D., and Christopherson, R. I. (1991) Biochem. Int. 24, 187-197). Three h after the addition of MTX (0.1 microM), cellular 5-phosphoribosyl-1-pyrophosphate has accumulated 3.4-fold while 6-methyl-mercaptopurine riboside (25 microM) induces a 6.3-fold accumulation. These data suggest that amido phosphoribosyltransferase catalyzing reaction 1 of the pathway is the primary site of inhibition. In support of this conclusion, we have found that dihydrofolate-Glu5, which accumulates in MTX-treated cells, is a noncompetitive inhibitor of amido phosphoribosyltransferase with a dissociation constant of 3.41 +/- 0.08 microM for interaction with the enzyme-glutamine complex in vitro. Folate-Glu5, MTX Glu5, PTX, dihydrotriazine benzenesulfonyl fluoride, and AICAR also inhibit amido phosphoribosyltransferase. PMID- 1597446 TI - Molecular details of the activation of soluble phospholipase A2 on lipid bilayers. Comparison of computer simulations with experimental results. AB - The initial rate of hydrolysis of large unilamellar vesicles of dipalmitoylphosphatidylcholine by phospholipase A2 from the venom of Agkistrodon piscivorus piscivorus is small and elevates gradually until it suddenly increases by a factor of 10 to 1000 depending on the experimental conditions. This abrupt onset of high enzyme activity appears to be correlated to a specific mole fraction of reaction product at which point a cooperative compositional phase transition in the bilayer occurs. Five models that describe the activation process in terms of its being coupled to the putative product-induced lipid transition are presented. These models include one in which the lipid structure enhances the affinity of enzyme binding to the bilayer surface, two in which the equilibrium position between an active and an inactive form of the enzyme substrate complex is altered, and two in which the rate of a quasi-irreversible spontaneous activation process is increased. Whether the active form of the enzyme is a monomer or dimer is also considered in the last two pairs of models. Computer simulations of time courses for the different models show how a set of four experimental observables distinguishes qualitatively among them. Comparison of the experimental behavior with the computer-simulated behavior of the observables for each model indicates that activation of phospholipase A2 on the lipid surface involves formation of an enzyme dimer which spontaneously converts to an active form. The active enzyme persists in the active state as it exchanges between vesicles. This model of activation is similar to that proposed previously for activation of porcine pancreatic phospholipase A2. PMID- 1597447 TI - Alternatively spliced variants of the human hepatic asialoglycoprotein receptor, H2, differ in cellular trafficking and regulation of phosphorylation. AB - The less abundant subunit of the asialoglycoprotein receptor, H2, may be encoded by at least four variant transcripts as a result of alternative mRNA splicing. We had cloned two H2-cDNAs that differed predominantly by the presence (clone H2') or absence (clone L-H2) of two presumed exons; one of 57 nucleotides was near the 5' end of the sequence, and the other was within the transmembrane region consisting of 15 nucleotides. The relevance of these two segments to H2 processing was studied after expression in rat-6 fibroblasts of these two isolates and of artificial constructs containing either only the 57-nucleotide (transfectant-57) or the 15-nucleotide (transfectant-15) region. H2 proteins encoded by cDNAs containing the 15-nucleotide region were intracellularly retained and degraded independently of the presence of the 57-nucleotide sequence. Of proteins derived from clones lacking the 15-nucleotide region, only a fraction was processed through the trans-Golgi, as evidenced by sensitivity to O-glycanase and neuraminidase, and reached the cell surface. The presence of the 57-nucleotide sequence was necessary for protein phosphorylation. Phosphorylation of serine residue(s) was detected in the endoglycosidase H-sensitive and mature forms of H2 protein encoded by transfectant-57. Since the 57-nucleotide region does not encode for serine residues, it per se cannot be the site of phosphorylation but rather constitutes a regulatory element for post translational modification. PMID- 1597448 TI - Isolation and characterization of a putative transcription factor involved in the regulation of the Rhodobacter sphaeroides pucBA operon. AB - The pucBA operon of the photosynthetic bacterium Rhodobacter sphaeroides encodes the light harvesting 2 (LH2) apoproteins of the photosynthetic apparatus, and transcription of this operon is markedly depressed under aerobic conditions. The region upstream of the LH2 genes has been subjected to gel retardation analysis, and two distinct bandshifts have been observed. The intensity of the upper bandshift was reduced upon lowering the oxygen tension under which the cells were grown, and this reduction preceded the appearance of LH2 in the cell membrane. Purification of the sequence-specific DNA binding protein responsible for this bandshift activity revealed a protein of M(r) 26,000, and DNase I footprint analysis revealed that the binding site was located 120 base pairs upstream of the transcription initiation point. We propose that this protein is an oxygen regulated repressor of pucBA transcription. This work, therefore, describes the first purification of a transcription factor from any photosynthetic bacterium. PMID- 1597449 TI - Multiple elements within the glucocorticoid regulatory unit of the rat alpha 1 acid glycoprotein gene are recognition sites for C/EBP. AB - Sequences between -106 and -42, located immediately downstream of the glucocorticoid response element, are essential for efficient glucocorticoid stimulated expression of the alpha 1-acid glycoprotein (AGP) gene. We have used mobility shift assays with oligonucleotides bearing wild type and mutated sequences from segmented portions of this region to characterize the specific interaction of similar binding factors from rat liver and HTC rat hepatoma cell nuclear extracts. One of these factors, AGP nuclear factor 2 (ANF-2), appears capable of dual interaction with the homologous recognition sites, HA (-133 to 104) and HB (-81 to -72), which overlap and are located downstream of the glucocorticoid response element, respectively. Using an affinity matrix containing the HB sequence we have isolated ANF-2 from rat liver nuclear extracts. On the basis of immunological evidence rat liver ANF-2 was confirmed to be highly related and probably identical to CCAAT/enhancer-binding protein (C/EBP). Methylation protection analyses with partially purified, rat liver ANF-2 confirmed HA and HB as recognition sites for C/EBP-related factors and are consistent with the location of a third interaction site for these transactivating proteins at HX (-102 to -93). We propose that the sequences HA, HX, and HB, spanning residues -113 to -72 of the AGP promoter, might serve as recognition sites for a family of C/EBP-like nuclear factors that coordinate the glucocorticoid-mediated induction of the AGP gene. PMID- 1597451 TI - Triplex formation prevents Sp1 binding to the dihydrofolate reductase promoter. AB - The human dihydrofolate reductase (DHFR) promoter sequence contains two consensus binding sites for the Sp1 regulatory protein. We have determined the effect of intermolecular triplex DNA formation on Sp1 binding to the DHFR promoter. The DHFR Sp1 binding site I (-39 to -48 relative to the DHFR transcription start site) demonstrates concentration-dependent triplex formation with a 19-base pair G-rich oligonucleotide (GR19) which is complementary to the polypyrimidine strand. DNase I footprint analysis demonstrates that GR19 forms a DNA triplex structure with the DHFR promoter fragment in a sequence-specific manner. DNase I footprinting analysis also indicates that the orientation of binding of these G rich oligonucleotides is antiparallel. CR19, a C-rich complementary oligonucleotide, on the other hand, does not form triplex. The DNase I protection pattern of DHFR promoter fragment incubated with both recombinant Sp1 and triplex forming oligonucleotide suggests that triplex formation prevents Sp1 binding. This is confirmed by gel shift analysis which demonstrates that triplex formation by the Sp1 binding sequences of the DHFR promoter prevents recombinant Sp1 binding in a concentration-dependent manner. These results demonstrate that intermolecular triplex formation prevents regulatory protein binding in a sequence-specific manner. PMID- 1597450 TI - Substrate specificity of neutral phospholipase D from rat brain studied by selective labeling of endogenous synaptic membrane phospholipids in vitro. AB - We have designed a novel approach for studying the specificity of neutral phospholipase D from rat brain synaptic plasma membranes for endogenous phospholipid substrates in native membranes. A procedure was established that provides synaptic membranes labeled in selected phospholipids. This labeling procedure exploits the presence of endogenous acyl-coenzyme A synthetase and acyl coenzyme A:lysophospholipid acyltransferase in synaptosomes for acylating various lysophospholipid acceptors with radioactive fatty acid. With [3H]arachidonate for acylation and optimal concentrations of the respective lysophospholipids, membranes were labeled in either of the following phospholipids: phosphatidylcholine (93% of total label in phospholipids), 1-O-alkyl phosphatidylcholine (87%), phosphatidylinositol (90%), phosphatidylethanolamine (85%), phosphatidylethanolamine-plasmalogen (81%) or phosphatidylserine (59%). These membranes were employed to study the substrate specificity of the neutral, oleate-activated rat brain phospholipase D. This phospholipase exhibited almost absolute specificity for the choline-phospholipids phosphatidylcholine and 1-O alkyl-phosphatidylcholine: 0.34% of the former labeled substrate were transphosphatidylated to phosphatidylpropanol during the assay and 0.28% of the latter. Activity toward other phospholipids was barely detectable and could largely be accounted for by utilization of residual labeled phosphatidylcholine present in those preparations. The phospholipase D exhibited some preference for fatty acids in the C-2 position of phosphatidylcholine in the following order: 2 oleoyl-phosphatidylcholine (0.67% of this labeled phosphatidylcholine were converted to phosphatidylpropanol), 2-myristoyl-phosphatidylcholine (0.60%), 2 palmitoyl-phosphatidylcholine (0.46%) and 2-arachidonoyl-phosphatidylcholine (0.34%). The present approach of labeling membrane phospholipids in vitro could be useful in studies of phospholipase specificity as an alternative to the use of sonicated vesicles or mixed detergent-phospholipid micellar systems. PMID- 1597452 TI - The role of negative supercoiling in Hin-mediated site-specific recombination. AB - A series of biochemical assays were developed and performed to monitor the molecular events that occur during the Hin-mediated DNA inversion reaction. These events can be divided into five different stages: 1) binding of proteins (Hin, Fis, and HU) to DNA; 2) pairing of Hin-binding sites; 3) invertasome formation; 4) DNA strand cleavage; 5) strand rotation and religation. A series of topoisomers of the wild type DNA substrate plasmid (ranging from fully relaxed molecules to those with more than the physiological superhelical density (the physiological superhelical density of pKH336 from Escherichia coli DH10B is 0.072 in this study)) was generated, and the role of negative supercoiling in each step of the inversion reaction was investigated. We found differences in the dependence of the formation of paired Hin-binding sites and of the invertasome formation on the superhelical density of the substrate plasmid. Pairing of Hin binding sites occurs independently from invertasome formation, and a relatively low degree of negative supercoiling is enough to promote maximal pairing. However, efficient invertasome formation requires higher levels of negative supercoiling. PMID- 1597453 TI - The effects of symmetrical recombination site hixC on Hin recombinase function. AB - An artificial recombination site hixC composed of two identical half-sites that bind the Hin recombinase served as a better operator in vivo than the wild type site hixL (Hughes, K. T., Youderian, P., and Simon, M. I (1988) Genes & Dev. 2, 937-948). In vitro binding assays such as gel retardation assay and methylation protection assay demonstrated that Hin binds to hixC as tightly as it binds to hixL, even when the sites are located in negatively supercoiled plasmids. However, hixC served as a poor recombination site when it was subjected to the standard inversion assay in vitro. hixC showed a 16-fold slower inversion rate than the wild type. A series of biochemical assays designed to probe different stages of the Hin-mediated inversion reaction, demonstrated that Hin dimers bound to hixC have difficulty in forming paired hix site intermediates. KMnO4 and S1 nuclease assays detected an anomalous structure of the center of hixC only when the site was in negatively supercoiled plasmids. Mutational analysis in the central region of hixC and assays of paired hix site formation with topoisomers of the hixC substrate plasmid suggested that Hin is not able to pair hixC sites because of the presence of the anomalous structure in the center of the site. The structure does not behave like a DNA "cruciform" since Hin dimers still bind efficiently to the site. It is thought to consist of a short denatured "bubble" encompassing 2 base pairs. During the study of mutations in the center of hixC, it was found that Hin is not able to cleave DNA if a guanine residue is one of the two central nucleotides close to the cleavage site. Furthermore, Hin acts in a concerted fashion and cannot cleave any DNA strand if one of the four strands in the inversion intermediate is not cleavable. PMID- 1597454 TI - Glucocorticoid-specific gene activation by the intact human glucocorticoid receptor expressed in yeast. Glucocorticoid specificity depends on low level receptor expression. AB - In the presence of appropriate reporter genes mammalian nuclear receptors are competent to transactivate gene expression when expressed in yeast cells. Thus yeast genetics could be used to identify determinants of steroid specificity for these mammalian proteins. However, unlike the estrogen, progesterone, vitamin D3, and thyroid hormone receptors, the glucocorticoid receptor shows an apparently abnormal steroid specificity in yeast (Schena, M., and Yamamoto, K. (1988) Science 241, 965-967), suggesting that the expressed protein might be incorrectly folded. We show here that the glucocorticoid receptor does exhibit a normal steroid specificity in yeast cells, but only at low levels of expressed receptor protein. Thus, at least under these conditions, genetic studies on steroid specificity are possible. At least part of the abnormal specificity that is sometimes observed for the glucocorticoid receptor in yeast appears to result from an artifact of the assay system and is not due to an abnormal receptor structure. This mechanism could account for all our data and so could provide the sole explanation of the abnormal specificity observed. However, it is also possible that part of the abnormal specificity could result from structural or other changes in receptor function, which occur when the receptor expression level is increased. PMID- 1597455 TI - Spontaneous cytosolic calcium oscillations driven by inositol trisphosphate occur during in vitro maturation of mouse oocytes. AB - Immature mouse oocytes undergo spontaneous meiotic maturation when released from antral follicles into culture media. The first sign of meiotic resumption is germinal vesicle breakdown (GVB). Cytosolic free Ca2+ was measured in mouse oocytes during spontaneous maturation by monitoring fluorescence of indo-1 or fluo-3. The majority of oocytes showed a series of Ca2+ oscillations that continued for 1-3 h. Repetitive Ca2+ increases occurred every 1-3 min and lasted for 10-60 s. The Ca2+ oscillations appeared to be caused by an increase in inositol 1,4,5-trisphosphate (InsP3) because once they ceased, similar oscillations were triggered by injection of exogenous InsP3. Also, injection of the InsP3 receptor antagonist heparin (final concentration, 100 micrograms/ml) blocked the spontaneous Ca2+ oscillations. In contrast, Ca2+ oscillations induced by thimerosal were not inhibited by heparin. Treating oocytes with media containing 20 microM BAPTA/AM abolished Ca2+ oscillations in oocytes but did not affect the rate of GVB. The data show that cytosolic Ca2+ oscillations apparently caused by polyphosphoinositide turnover occur during mammalian oocyte maturation. However, the spontaneous oscillations do not appear to trigger GVB. Also, the data indicate that there are two separate Ca2+ release mechanisms in mouse oocytes, one sensitive to InsP3, the other to thimerosal. PMID- 1597456 TI - Mechanism of increased conversion of branched chain keto acid dehydrogenase from inactive to active form by a medium chain fatty acid (octanoate) in skeletal muscle. AB - We and others have previously shown that octanoate increases the oxidation of branched chain amino acids (BCAA) in skeletal muscle. The present study was designed to investigate the mechanism of this increased oxidation. Studies were performed with rat hind limbs perfused with 0.50 mM L-[1-14C]leucine with or without octanoate. The flux through branched chain keto acid (BCKA) dehydrogenase was measured, and the basal and total activity of BCKA dehydrogenase in skeletal muscle was determined. The rate of flux through BCKA dehydrogenase increased by 37, 119, and 297% with 0.5, 1.0, and 2.0 mM octanoate, respectively. This increase in flux was not due to a change in BCAA aminotransferase activity but was due to an increase in the basal activity of BCKA dehydrogenase. There was a strong correlation (r = 0.96) between increases in flux through BCKA dehydrogenase and increases in the basal activities of BCKA dehydrogenase. Preincubation of BCKA dehydrogenase with Mg2+ caused full activation of this enzyme, but preincubation with octanoate did not activate this enzyme. On the other hand, octanoate completely prevented the ATP-dependent inactivation of fully activated BCKA dehydrogenase. We conclude that octanoate increases the oxidation of leucine in skeletal muscle by increasing the activation of BCKA dehydrogenase. The mechanism of this activation is the inhibition of BCKA dehydrogenase kinase rather than the stimulation of a specific or nonspecific protein phosphatase. PMID- 1597457 TI - The primary determinant of rabbit myocardial ethanolamine phosphotransferase substrate selectivity is the covalent nature of the sn-1 aliphatic group of diradyl glycerol acceptors. AB - Plasmenylethanolamines represent the major endogenous phospholipid storage depot of arachidonic acid in many mammalian cells. To elucidate the biochemical mechanisms contributing to the high plasmalogen content and arachidonic acid enrichment present in myocardial ethanolamine glycerophospholipids, the substrate specificity of rabbit myocardial ethanolamine phosphotransferase (EPT) was quantified utilizing multiple molecular species of each subclass of diradyl glycerol substrate. Myocardial EPT demonstrated over a 16-fold selectivity for 1 O-alk-1'-enyl-2-acyl-sn-glycerol (AAG) compared to 1,2-diacyl-sn-glycerol (DAG) substrate utilizing individual molecular species of each subclass dispersed in Tween 20. The selective utilization of AAG by EPT was substantiated utilizing two independent assay systems which employed either the presentation of substrate to enzyme as a substitutional impurity in Triton X-100 mixed micelles or the obligatory utilization of endogenously generated diradyl glycerol substrates. Although rabbit myocardial microsomes contained over a 20-fold molar excess of endogenous DAG to AAG mass, incubation of rabbit myocardial microsomes with CDP ethanolamine resulted in the highly selective synthesis of plasmenylethanolamines which were predominantly comprised of molecular species containing arachidonic acid at the sn-2 position (greater than 75%). Endogenous AAG molecular species in rabbit myocardial microsomes were similarly enriched in arachidonic acid, and the distribution of AAG molecular species closely paralleled the distribution of plasmenylethanolamine (but not plasmenylcholine) molecular species. Thus, the subclass and molecular species distribution of the ethanolamine glycerophospholipids synthesized by rabbit myocardial EPT reflects independent contributions from the subclass selectivity of EPT for AAG substrate in conjunction with the enrichment of arachidonic acid in microsomal AAG molecular species. PMID- 1597458 TI - Lactoferrin uptake by the rat liver. Characterization of the recognition site and effect of selective modification of arginine residues. AB - Recently it was found that lactoferrin, an iron-binding glycoprotein with a molecular weight of 76,500, inhibits the remnant receptor-mediated uptake of apolipoprotein E (apoE)-bearing lipoproteins by the liver. In the present study we characterized the hepatic recognition of lactoferrin. Intravenously injected 125I-lactoferrin was cleared rapidly from the circulation by the liver (92.8 +/- 9.5% of the dose at 5 min after injection). Parenchymal cells contained 97.1 +/- 1.5% of the hepatic radioactivity. Internalization, monitored by measuring the release of liver-associated radioactivity by the polysaccharide fucoidin, occurred slowly. Only about 40% of the liver-associated lactoferrin was internalized at 10 min after injection, and it took 180 min to internalize 90%. Subcellular fractionation indicated that internalized lactoferrin is transported to the lysosomes. Binding of lactoferrin to isolated parenchymal liver cells was saturable with a dissociation constant of 10 microM (20 x 10(6) binding sites/cell). The role of arginine residues on lactoferrin was studied by modifying these residues with 1,2-cyclohexanedione. The modification resulted in a strongly reduced liver association (15.9 +/- 1.6% of the dose at 5 min after injection). Furthermore, unlabeled 1,2-cyclohexanedione-modified lactoferrin did not inhibit the binding of 125I-lactoferrin to isolated parenchymal cells. Arginine residues on lactoferrin thus appear to be essential for its specific recognition by parenchymal liver cells. In particular the clustered N-terminal arginine residues, which resemble the arginine-rich receptor binding sequence in apoE, may be responsible for both the interaction of lactoferrin with its recognition site and the inhibition of the hepatic uptake of apoE-bearing lipoproteins. PMID- 1597459 TI - Effects of pH and Ca2+ on monomer-dimer and monomer-tetramer equilibria of chromogranin A. AB - Chromogranin A is a high capacity, low affinity Ca2+ binding protein which undergoes Ca2+- and pH-dependent conformational changes, and has recently been suggested to play a Ca2+-buffering role in the secretory vesicle of adrenal medullary chromaffin cell, the major inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store of chromaffin cell (Yoo, S.H., and Albanesi, J.P. (1990) J. Biol. Chem. 265, 13446-13448). In the present study, it is shown that chromogranin A exists in a monomer-dimer equilibrium at pH 7.5 and in a monomer tetramer equilibrium at pH 5.5. The pH appears monomer-tetramer equilibrium at pH 5.5. The pH appears to be a necessary and sufficient factor determining the types of oligomers formed. Although Ca2+ did not change the type of oligomerization, it had a very significant effect on the values of the thermodynamic parameters characterizing the associations. The delta G0 values for a monomer-dimer equilibrium were -7 to -8 kcal/mol, while those for a monomer-tetramer equilibrium were -20 to -23 kcal/mol. At pH 5.5, the values of delta H0, delta S0, and delta C0p were large and negative in the absence of Ca2+ and large and positive in the presence of 35 mM Ca2+, implying markedly different reaction mechanisms. Extrapolation of the results to 37 degrees C and 1 mM chromogranin A suggests that chromogranin A is virtually 100% tetramer at pH 5.5 in the presence of 35 mM Ca2+ but is 96% dimer at pH 7.5 in the absence of Ca2+, the two conditions resembling those seen in vivo. These results suggest that chromogranin A is mostly dimer in the endoplasmic reticulum and cis-Golgi area and is essentially all tetramer in the vesicle. PMID- 1597460 TI - Peptidoglycan composition of a highly methicillin-resistant Staphylococcus aureus strain. The role of penicillin binding protein 2A. AB - All clinical isolates of methicillin-resistant Staphylococcus aureus contain an extra penicillin binding protein (PBP) 2A in addition to four PBPs present in all staphylococcal strains. This extra PBP is thought to be a transpeptidase essential for the continued cell wall synthesis and growth in the presence of beta-lactam antibiotics. As an approach of testing this hypothesis we compared the muropeptide composition of cell walls of a highly methicillin-resistant S. aureus strain containing PBP2A and its isogenic Tn551 derivative with reduced methicillin resistance, which contained no PBP2A because of the insertional inactivation of the PBP2A gene. Purified cell walls were hydrolyzed into muropeptides which were subsequently resolved by reversed-phase high-performance liquid chromatography and identified by chemical and mass spectrometric analysis. The peptidoglycan composition of the two strains were identical. Both peptidoglycans were highly cross-linked mainly through pentaglycine cross bridges, although other, chemically distinct peptide cross-bridges were also present including mono-, tri-, and tetraglycine; alanine; and alanyl tetraglycine. Our experiments provided no experimental data for a unique transpeptidase activity associated with PBP2A. PMID- 1597461 TI - A novel transiently expressed, integral membrane protein linked to cell activation. Molecular cloning via the rapid degradation signal AUUUA. AB - A novel cDNA clone termed E16 which codes for an integral membrane protein of 241 amino acids with six transmembrane domains was isolated from peripheral blood lymphocytes. The cDNA clone is 4000 base pairs in length and exhibits an unusually long 3'-untranslated region of about 3000 nucleotides. Its expression at the mRNA level is closely linked to cellular activation and division. In all myeloid and lymphoid cells, as well as in primary lymphocytes from peripheral blood, E16 transcripts are rapidly induced and rapidly degraded after stimulation. This pattern of expression is unusual for an integral membrane protein and resembles more closely the kinetic seen for protooncogenes and lymphokines in the T cell system. Its isolation was made possible by a novel approach especially designed to selectively clone cDNAs which exhibit such an expression kinetic. It is based on a combination of the differential screening of a subtracted cDNA library and the subsequent hybridization of the resulting phages to a short oligonucleotide (5'-TAAATAAA-TAAATA-3'). This oligonucleotide is complementary to a trimer of the rapid degradation signal (AUUUA) which is present as a single or reiterated motif in the 3'-untranslated region of many short-lived transcripts. PMID- 1597462 TI - CDC14 of Saccharomyces cerevisiae. Cloning, sequence analysis, and transcription during the cell cycle. AB - We have cloned, mapped and sequenced the complete CDC14 gene of Saccharomyces cerevisiae and characterized its transcription during the cell cycle. CDC14 was found within a 3.5-kilobase pair XhoI-XbaI fragment of chromosome VI. The DNA sequence reveals an open reading frame capable of encoding a 423-amino acid polypeptide. Protein sequence comparisons through the Prosite, GenBank and EMBL databases allowed us to identify a conserved protein tyrosine phosphatase active site in the encoded CDC14 protein beginning at amino acid 153. Disruption demonstrates that CDC14 is an essential gene. The level of the CDC14 transcript appears to be weakly cell cycle-regulated and has a periodicity which lags approximately 15 min behind histone HTB1 mRNA accumulation levels. DNA sequence analysis has identified a region within the CDC14 promoter which bears a striking resemblance (15 out of 21 base pairs identity) to the cell cycle regulation region of the promoter of the histone H2A1-H2B1 (HTA1-HTB1) gene pair. The cell cycle regulation sequence is responsible for the periodic accumulation and hydroxyurea sensitivity of the histone HTA1-HTB1 message. However, unlike histone mRNA, which is repressed upon hydroxyurea arrest, CDC14 mRNA appears to be unaffected. This suggests that CDC14 and histone genes are regulated by different mechanisms during the cell cycle. Furthermore, superhelical density measurements suggest that CDC14 is not involved in nucleosome assembly. PMID- 1597463 TI - Effects of the neuronal phosphoprotein synapsin I on actin polymerization. II. Analytical interpretation of kinetic curves. AB - The general features of the kinetics of actin polymerization are investigated by mathematical models, with the aim of identifying the kinetically relevant parameters in the process and detecting and interpreting the alterations occurring in actin polymerization under various experimental conditions. Polymerization curves, obtained by following the increase in fluorescence of actin derivatized with N-(1-pyrenyl) iodoacetamide, are fitted using analytical equations derived from biochemical models of the actin polymerization process. Particular attention is given to the evaluation of the effects of the neuronal phosphoprotein synapsin I. The models obtained under various ionic conditions reveal that synapsin I interacts with actin in a very complex fashion, sharing some of the properties of classical nucleating proteins but displaying also actions not described previously for other actin-binding proteins. Synapsin I appears to bind G-actin with a very high stoichiometry (1:2-4), and the complex behaves as an F-actin nucleus, producing actin filaments under conditions where spontaneous polymerization is negligible. These actions of synapsin I are markedly affected by site-specific phosphorylation of the protein. An original transformation of the fluorescence data, which estimates the disappearance rate of actin monomer toward the critical concentration, is presented and shown to be of general usefulness for the study of actin-binding proteins. PMID- 1597464 TI - Modulation of platelet function through adhesion receptors. A dual role for glycoprotein IIb-IIIa (integrin alpha IIb beta 3) mediated by fibrinogen and glycoprotein Ib-von Willebrand factor. AB - We have found that the form of glycoprotein (GP) IIb-IIIa (integrin alpha IIb beta 3) expressed on nonstimulated platelets is a functional receptor that mediates selective and irreversible adhesion to immobilized fibrinogen. This occurs even in the presence of the elevated intracellular cAMP levels induced by prostaglandin E1 or after inhibition of protein kinase C activity by sphingosine. In the absence of inhibitors, platelets adhering to fibrinogen through GP IIb IIIa become fully activated and aggregate with one another. Immobilized von Willebrand factor (vWF), in contrast, is recognized by nonstimulated platelets through another receptor, GP Ib. This interaction leads to a change in the ligand recognition specificity of GP IIb-IIIa that can then bind to immobilized vWF and mediate irreversible platelet adhesion and aggregation; this process, however, is inhibited by elevated intracellular cAMP levels or blockade of protein kinase C activity. Therefore, GP Ib and GP IIb-IIIa induce platelet activation through the selective recognition of immobilized vWF and fibrinogen, respectively, in the absence of exogenous agonists. Moreover, "nonactivated" and "activated" GP IIb IIIa exhibits distinctly different reactivity toward surface-bound vWF, and the functional switch can be induced by the binding of vWF to GP Ib. These findings demonstrate the modulation of platelet function by two different adhesion receptors, GP Ib and GP IIb-IIIa, as well as the distinct dual role of the latter as the necessary common mediator of irreversible adhesion and aggregation on both fibrinogen and vWF. PMID- 1597465 TI - The efficiency of promoter clearance distinguishes T7 class II and class III promoters. AB - Promoter strength has been defined as the relative production of transcripts from a promoter. For T7 transcription it has frequently been observed that T7 class III promoters are qualitatively stronger than T7 class II promoters. In previous work it was observed that the maximum rates of initiation of three class III and three class II promoters show no class distinctions (Ikeda, R. A., Lin, A. C., and Clarke, J. (1992) J. Biol. Chem. 267, 2640-2649). This suggests that the efficiency of the conversion of the polymerase initiation complex to a stable transcription complex contributes to the overall strength of T7 promoters. The class differences in the strengths of T7 class II and class III promoters are confirmed by measuring the relative synthesis of run-off transcripts. These results show that the relative strengths of the class III promoters, phi 6.5, phi 10, and phi 13, are all comparable ranging from 0.61 for phi 6.5 to 1.00 for phi 10, while the relative strengths of the T7 class II promoters, phi 1.1B, phi 1.3, and phi 3.8, vary widely. One T7 class II promoter, phi 1.1B (relative strength = 0.34), approaches the strength of the class III promoters, while the other T7 class II promoters, phi 1.3 (relative strength = 0.045) and phi 3.8 (relative strength = 0.070) are nearly inactive. The efficiency of promoter clearance is then determined by measuring the relative production of small transcription products in comparison with the production of run-off transcripts. These measurements clearly distinguish the T7 class III promoters from the T7 class II promoters. It is found that 68-75% of all initiations at the T7 class III promoters phi 6.5, phi 10, and phi 13 produce a run-off transcript, while only 16 36% of the initiations at the T7 class II promoters phi 1.1B, phi 1.3, and phi 3.8 produce a run-off transcript. Clearly, promoter clearance contributes to the difference in promoter strengths of the T7 class II and III promoters. PMID- 1597466 TI - Post-translational processing of Schizosaccharomyces pombe YPT proteins. AB - ras proteins are post-translationally processed at their carboxyl-terminal CAAX motif by a triplet of modifications: prenylation of C with farnesyl, proteolytic trimming of AAX, and carboxyl-methylation. These modifications co-operate with palmitoylation of nearby sites or a polybasic region to target plasma membrane localization. The related YPT/rab proteins in contrast are localized to compartments of the endo-membrane system and may be involved in directing membrane traffic. These proteins end in XCC or CXC motifs. We have analyzed the processing of members of this subfamily form the fission yeast Schizosaccharomyces pombe. We find using in vitro translation in reticulocyte lysates that YPT1, -3, and -5 are prenylated with geranylgeranyl and that they incorporate label from [3H]mevalonic acid when expressed in transfected COS cells in vivo. Furthermore, prenylation was necessary for membrane binding in vivo. The CXC protein YPT5, but neither of the two XCC proteins YPT1 and YPT3, was carboxyl methylated in S. pombe and in COS cells in vivo. However, YPT5 was not carboxyl methylated in vitro in lysates which were able to methylate ras protein. YPT3 was detectably palmitoylated when expressed in COS cells, though at a much lower level than ras. PMID- 1597468 TI - Substitution of lysine 213 with arginine in penicillin-binding protein 5 of Escherichia coli abolishes D-alanine carboxypeptidase activity without affecting penicillin binding. AB - All penicillin-binding proteins (PBPs) contain a conserved box of homology in the carboxyl-terminal half of their primary sequence that can be Lys-Thr-Gly, Lys-Ser Gly, or His-Thr-Gly. Site-saturation mutagenesis was used to address the role of the lysine residue at this position (Lys213) in Escherichia coli PBP 5, a D alanine carboxypeptidase enzyme. A soluble form of PBP 5 was used to replace Lys213 with 18 other amino acids, and the ability of these mutant proteins to bind [3H]penicillin G was assessed. Only the substitution of lysine with arginine resulted in a protein that was capable of forming a stable covalent complex with antibiotic. The affinity of [14C]penicillin G for the arginine mutant was 1.2 fold higher than for wild-type PBP 5 (4.4 versus 5.1 micrograms/ml for 20 min at 30 degrees C), and both proteins showed identical rates of hydrolysis of the [14C]penicilloyl-bound complex (t1/2 = 9.1 min). Surprisingly, the arginine substituted protein was unable to catalyze D-alanine carboxypeptidase activity in vitro, which suggests that there is a substantial difference in the geometries of the peptide substrate and penicillin G within the active site of PBP 5. PMID- 1597467 TI - Role of cysteines 640, 656, and 661 in steroid binding to rat glucocorticoid receptors. AB - The involvement of a vicinally spaced dithiol group in steroid binding to the glucocorticoid receptor has been deduced from experiments with the thiol-specific reagent methyl methanethiolsulfonate and the vicinal dithiol-specific reagent sodium arsenite. The vicinally spaced dithiol appears to reside in the 16-kDa trypsin fragment of the receptor, which is thought to contain 3 cysteines (Cys 640, -656, and -661 of the rat receptor) and binds hormone with an approximately 23-fold lower affinity than does the intact 98-kDa receptor. We now report that the steroid binding specificity of preparations of this 16-kDa fragment and the intact receptor are virtually identical. This finding supports our designation of the 16-kDa fragment as a steroid-binding core domain and validates our continued use of this tryptic fragment in studies of steroid binding. To identify the cysteines which comprise the vicinally spaced dithiol group, and to examine further the role of cysteines in steroid binding, a total of five point mutant receptors were prepared: cysteine-to-serine for each suspected cysteine, cysteine to-glycine for Cys-656, and the C656,661S double mutant. Unexpectedly, each receptor with a single point mutation still bound steroid. Even the double mutant (C656,661S) bound steroid with wild type affinity. These results suggest that none of these cysteines are directly required either for steroid binding to the glucocorticoid receptor or for heat shock protein 90 association with the receptor. However, the presence of Cys-656 was obligatory for covalent labeling of the receptor by [3H]dexamethasone 21-mesylate. Studies with preparations of the 98 and 16 kDa forms of these mutant receptors revealed both that Cys-656 and 661 comprise the vicinally spaced dithiols reacting with arsenite and that any two of the three thiols could form an intramolecular disulfide after treatment with low concentrations of methyl methanethiolsulfonate. These data, in conjunction with those from experiments on the effects of steric bulk on various receptor functions, support a model for the ligand binding cavity of the receptor that involves all three thiols in a flexible cleft but where thiol-steroid interactions are not essential for binding. PMID- 1597469 TI - Purified MotA protein binds the -30 region of a bacteriophage T4 middle-mode promoter and activates transcription in vitro. AB - The bacteriophage T4-encoded MotA protein is critical for transcription from T4 middle-mode promoters. However, a direct interaction of this protein with a middle-mode promoter has not previously been demonstrated. We have cloned the motA gene and overexpressed the gene product using the T7 expression system. A simple procedure was then developed to purify the MotA protein to homogeneity. Using the purified protein we have demonstrated that MotA protein binds to the 30 region of the middle-mode promoter PuvsY. This promoter has previously been shown to be a necessary component of a T4 replication origin, and thus MotA is also a T4 origin-binding protein. Modified RNA polymerase purified from T4 infected cells was used to establish middle-mode transcription in vitro. Transcription from PuvsY was markedly enhanced by the addition of MotA protein, whether or not the template contained the cytosine modifications characteristic of T4 DNA. However, transcription from PuvsY was apparently independent of the MotA protein when unmodified RNA polymerase from uninfected cells was used. PMID- 1597470 TI - Secretion and biological activities of heparin-binding growth-associated molecule. Neurite outgrowth-promoting and mitogenic actions of the recombinant and tissue-derived protein. AB - The cDNA for the developmentally regulated, neurite outgrowth-promoting protein HB-GAM (heparin-binding growth-associated molecule) was recently cloned and shown to encode a novel lysine-rich sequence that is homologous with retinoic acid induced sequences suggested to function in cell differentiation (Merenmies, J., and Rauvala, H. (1990) J. Biol. Chem. 265, 16721-16724). The same sequence was found for the mitogenic and neurite outgrowth-promoting protein pleiotrophin (Li, Y.-S., Milner, P. G., Chauhan, A. K., Watson, M. A., Hoffman, R. M., Kodner, C. M., Milbrandt, J., and Deuel, T. F. (1990) Science 250, 1690-1694). In this study, we have constructed a recombinant baculovirus using the cDNA that encodes the putative preprotein of HB-GAM. The putative secretion signal of HB-GAM is cleaved off in the baculovirus expression system, and the recombinant protein is rapidly secreted to the culture medium. Recombinant HB-GAM purified from the culture medium retains the biochemical characteristics and the neurite outgrowth promoting activity found for the tissue-derived protein. Studies on the neurite outgrowth-promoting activity suggest that HB-GAM functions as an extracellular matrix-associated protein that enhances axonal growth in perinatal cerebral neurons of the rat. Since the same predicted amino acid sequence has been ascribed to a mitogenic protein, mitogenic activities of the recombinant HB-GAM and of tissue-derived HB-GAM fractions were also studied. Recombinant HB-GAM did not display any significant mitogenic activity, suggesting that tissue-derived HB GAM preparations may contain other heparin-binding mitogenic factors. We identified in brain-derived HB-GAM fractions a 17-kDa protein (p17) that is detached from heparin by a slightly higher salt concentration as compared to HB GAM. We suggest that p17 is structurally distinct from HB-GAM and responsible for the mitogenic actions of tissue-derived HB-GAM fractions. PMID- 1597471 TI - Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1. AB - Proprotein and prohormone processing at pairs of basic residues is generally thought to be both tissue- and precursor-specific and to be developmentally regulated. Furin, PC1 (also called PC3), and PC2 represent three recently discovered subtilisin-like proteinases which cleave a number of precursors at the same pairs of basic residues normally processed in vivo. Using human prorenin as a model, we show that PC1 can process it to active renin in cells containing secretory granules, such as the somatomammotroph cell line GH4, but not in cells which lack granules, such as the Chinese hamster ovary or African green monkey kidney epithelial (BSC-40) cell lines. In contrast, in both cell types, human prorenin is not activated by either PC2 or furin. Using the vaccinia virus expression system, biosynthetic labeling experiments demonstrated that PC1 and PC2 are themselves cleaved intracellularly at pairs of basic residues and that these two proenzymes are processed to different extents independent of whether the cell line contains dense core secretory granules. Furthermore, we also show that the cells mostly secrete the cleaved forms of PC1 and PC2, and that intracellularly the pro- form of PC2 predominates. Our data demonstrate that propeptide removal from these enzymes, possibly leading to their activation, is not the only criterion which governs precursor processing. PMID- 1597472 TI - The 260-kDa transforming growth factor (TGF)-beta binding protein in rat glomeruli is a complex comprised of 170- and 85-kDa TGF-beta binding proteins. AB - In a previous study (MacKay, K., Robbins, A. R., Bruce, M. D., and Danielpour, D. (1990) J. Biol. Chem. 265, 9351-9356) we showed that rat glomeruli contain transforming growth factor (TGF)-beta 1 binding proteins with apparent molecular masses of 260, 170, and 85 kDa (Gl-260, Gl-170, Gl-85) as determined by electrophoresis under nonreducing conditions. We demonstrate here that Gl-260 is a complex of 170- and 85-kDa TGF-beta binding proteins. Under denaturing conditions the integrity of Gl-260 is maintained through the cross-linking of one monomer of the disulfide-linked TGF-beta 1 homodimer to Gl-85 and of the other monomer to the 100-kDa subunit of Gl-170. In addition, some Gl-260 complexes are maintained by direct cross-linking of Gl-85 to the 100-kDa subunit of Gl-170. One dimensional peptide maps of Gl-85 and the 100-kDa subunit of Gl-170 indicate that they have distinctly different ligand binding domains. In contrast, peptide maps of Gl-85 and the type II receptor of normal rat kidney fibroblasts are similar. The biological responses of isolated glomeruli to TGF-beta appear to parallel those of cultured glomerular cells which are without detectable Gl-170 and Gl-260 binding proteins. PMID- 1597473 TI - Rat cystathionine beta-synthase. Gene organization and alternative splicing. AB - We elucidated the structure and alternative splicing patterns of the rat cystathionine beta-synthase gene. The gene is 20-25 kilobase pairs long, and its coding region is divided into 17 exons. These are alternatively spliced, forming four distinct mRNAs (types I through IV). The predicted open reading frames encode proteins of 61.5, 39, 60, and 52.5 kDa, respectively. Exons 13 and 16 are used alternatively and mutually exclusively. Exon 13 includes a stop codon and encodes the unique carboxyl-terminal sequence found in types II and IV. Exon 16 is present only in type I. Types I and III, which differ by 42 nucleotides (exon 16), are the predominant synthase mRNA forms in rat liver. Seventeen arginine peptides from pure liver synthase matched the deduced amino acid sequences of types I and III. These two polypeptides are detectable in liver extracts; each exhibits enzymatic activity when expressed in transfected Chinese hamster cells. Synthase shows substantial sequence similarity with pyridoxal 5'-phosphate dependent enzymes from lower organisms. Similarity of synthase to Escherichia coli O-acetylserine (thiol)-lyase (cysK) is 52%; E. coli tryptophan synthase beta chain (trpB), 36%; yeast serine deaminase, 33%. Lysine 116 in synthase aligns with the established pyridoxyllysine residue of these enzymes suggesting that it is the pyridoxal 5'-phosphate binding residue. PMID- 1597474 TI - Pulmonary epithelial cell urokinase-type plasminogen activator. Induction by interleukin-1 beta and tumor necrosis factor-alpha. AB - Diffuse alveolar damage, presenting clinically as adult respiratory distress syndrome, is characterized initially by widespread intra-alveolar fibrin deposition. Alveolar epithelial cells play a central role in the subsequent repair process. We have recently shown that alveolar epithelial cells have the capacity to promote fibrinolysis (Marshall, B. C., Sageser, D. S., Rao, N. V., Emi, M., and Hoidal, J. R. (1990) J. Biol. Chem. 265, 8198-8204) and may therefore directly participate in the extensive remodeling that follows acute lung injury. Because the tissue repair process occurs in an acute inflammatory setting, we investigated the effects of inflammatory mediators on urokinase-type plasminogen activator (u-PA) expression by pulmonary epithelial cells. We found that interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) upregulated PA activity in A549 human pulmonary epithelial cells. Biosynthetic labeling and immunoprecipitation showed that both cytokines caused marked accumulation of newly synthesized u-PA. Northern blot analyses demonstrated that both IL-1 beta and TNF-alpha induced relatively rapid accumulation of u-PA mRNA which did not require de novo protein synthesis and was substantially inhibited by glucocorticoids. Nuclear run-off transcription studies showed that both cytokines caused rapid transcriptional activation of the u-PA gene. While the effects of IL-1 beta and TNF-alpha were qualitatively similar, some differences emerged. Most notably, TNF-alpha led to a more sustained accumulation of u-PA mRNA than did IL-1 beta. In contrast to their effects on u-PA expression, IL-1 beta and TNF-alpha had minimal effect on PA inhibitor-1 expression. These effects of IL-1 beta and TNF-alpha, mediators known to play a key role in acute lung injury and inflammation, may promote lysis of alveolar fibrin by alveolar epithelium, thereby aiding in restoration of normal lung architecture. PMID- 1597475 TI - A novel mechanism for achieving transgene persistence in vivo after somatic gene transfer into hepatocytes. AB - Infusion of hepatocyte-specific DNA-protein complexes into rats leads to transient recombinant gene expression in liver. The eventual deterioration of gene expression is due in part to instability of the targeted DNA. In a previous report, we noted retention of transgene sequences in liver and persistent recombinant gene expression when the animals were subjected to partial hepatectomy following in vivo gene transfer. In an attempt to define the mechanism(s) responsible for persistent gene expression following partial hepatectomy, we characterized the molecular state of the retained, liver associated transgenes. Southern blot analysis of DNA from liver tissues harvested various times after in vivo gene transfer and partial hepatectomy (10 min to 11 weeks) demonstrated high levels of transgene DNA (100-10,000 copies/cell). The predominant form of this DNA appeared to be episomal based on analyses of uncut DNA or DNA restricted by an endonuclease with one site in the plasmid. Livers from several animals contained a small proportion of transgene sequences of unknown structure. The existence of episomal DNA in liver was confirmed in experiments in which intact plasmid was rescued from total hepatocyte DNA by transformation of bacteria. Both strands of DNA in the liver-associated plasmid retained a bacterial pattern of methylation suggesting that the plasmid had not replicated in the eukaryotic cell. These results are consistent with the hypothesis that the majority of transgene sequences are retained as stabilized plasmids. The specific form of DNA which is transcriptionally active was not identified in these studies. This represents a new mechanism for retaining foreign DNA in eukaryotic cells in vivo and has implications both for the development of somatic gene therapies and the pathogenesis of viral diseases. PMID- 1597476 TI - Sealed reticulocyte ghosts. An experimental model for the study of Fe2+ transport. AB - Sealed right-side-out reticulocyte ghosts transported and accumulated iron offered as 59Fe(2+)-ascorbate (Km = 1.1 microM). The uptake of iron by ghosts presented the characteristics of a transporter-mediated process: it responded to osmotic challenge, the rate of transport increased when iron was present in the opposing side, and the transport rate showed the temperature dependence typical of membrane-mediated processes. The transport of iron was dependent on an associated influx of Cl- in order to keep electroneutrality. Other transition metals, such as Cu2+, Zn2+, and Co2+, inhibited the transport of Fe2+. The overall characteristics of the system make reticulocyte sealed ghosts a very useful model in determining the basic mechanisms of membrane iron transport. PMID- 1597477 TI - Modulation of eucaryotic initiation factor-4E binding to 5'-capped oligoribonucleotides by modified anti-sense oligonucleotides. AB - The 5' cap structure of eucaryotic mRNA plays a pivotal role in mRNA metabolism. This report demonstrates that anti-sense oligonucleotides equipped with 3' overhanging nucleotides modulate the amount of recombinant human eucaryotic initiation factor-4E that binds to a 5'-capped oligoribonucleotide. The degree of inhibition or enhancement of protein binding is dependent upon the number and sequence of overhanging nucleotides. A 45% inhibition of complexation was observed by the addition of one 3'-overhanging guanosine residue. Addition of a second residue (+2/GN) resulted in a higher degree of inhibition, 77-88%. In contrast, addition of one adenosine residue enhanced the formation of the eucaryotic initiation factor-4E-m7GpppRNA complex by 213%. Modulation of protein interactions with the 5'-cap structure is likely to effect several biological events, including pre-mRNA processing, transport of the mRNA from the nucleus to the cytoplasm and translation of the target mRNA. This targeting strategy in anti sense chemistry may have practical applications in experimental biology and medicine. PMID- 1597478 TI - Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements. AB - Protein disulfide isomerase (PDI) is a highly unusual multifunctional polypeptide that is identical to the beta-subunit of prolyl 4-hydroxylase, a cellular thyroid hormone-binding protein and a subunit of the microsomal triglyceride transfer protein complex, and very similar to a polypeptide functioning in vitro as a glycosylation site binding protein of oligosaccharyl transferase. The human PDI gene possesses several putative transcriptional control elements, including the highly unusual presence of six CCAAT boxes between -108 and -378 of the 5' flanking region. We report here on a promoter analysis of this gene. Eleven PDI promoter elements recognized by DNA-binding proteins present in HeLa cell and HT 1080 cell nuclear extracts were identified by DNase I footprinting analysis within the first 630 nucleotides of the 5'-flanking region. Interestingly, these included all six CCAAT elements. Functional 5' deletion analysis suggested that only two or three of the CCAAT elements may contribute significantly to the promoter activity in HeLa cells. Mutations introduced into each of the CCAAT boxes separately indicated, however, that all six appear to contribute to the promoter strength, the largest decreases (approximately 50%) being seen with mutations in the second or fifth CCAAT box. These data thus suggested that efficient expression of the multifunctional PDI polypeptide is secured by multiple CCAAT elements, some of which appear to be functionally redundant. The 5' deletion analysis further suggested that a region between -623 and -518 may contain additional positively and negatively acting elements. PMID- 1597479 TI - Binding of RepE initiator protein to mini-F DNA origin (ori2). Enhancing effects of repE mutations and DnaJ heat shock protein. AB - Replication of mini-F plasmid in Escherichia coli requires the plasmid-encoded RepE initiator protein and a number of host factors and is regulated by interaction of RepE with specific sequences near the replication origin, ori2. We have examined DNA binding properties of several hyperactive mutant RepE proteins with single amino acid substitutions. Plasmids carrying these (repE) mutations, unlike the parental plasmid, can replicate in bacterial hosts lacking the heat shock sigma factor (sigma 32) or deficient in the DnaK, DnaJ, or GrpE heat shock protein. Using gel-retardation assays, the mutant RepE proteins were shown to bind the ori2 repeated sequences with much increased affinities compared to the wild type RepE, whereas they bound to the repE operator with slightly reduced affinities. These results agreed well with the properties of mutant RepE proteins studied in vivo and accounted for the high RepE initiator activities and the high copy numbers of mutant plasmids. In addition, the DnaJ heat shock protein was found to markedly enhance the binding of wild type RepE to ori2 or the operator. DnaK protein with or without ATP failed to show such enhancements. Thus, among the heat shock proteins required for mini-F replication, DnaJ appears to play a major role in RepE binding to ori2 and the operator, perhaps accompanied by RepE activation. PMID- 1597480 TI - Selective translocation of the A chain of diphtheria toxin across the membrane of purified endosomes. AB - Translocation is a necessary and rate-limiting step for diphtheria toxin (DT) cytotoxicity. We have reconstituted DT translocation in a cell-free system using endosomes purified from lymphocytes and have demonstrated this using two different probe/cell systems, which provided identical results: 125I-DT/human CEM cells and 125I-transferrin-DT/mouse BW cells. The cell-free DT translocation process was found to be dependent on the presence of the pH gradient endosome (pH 5.3)/cytosol (pH 7). Among the pH equilibrating agents, nigericin (5 microM) was found to be the most effective, inhibiting DT translocation by 88%. An optimum pH value of 7 on the cytosolic side of the membrane (pH gradient approximately 1.7) was determined. ATP per se is not required for DT translocation. 125I-DT translocation was 3-fold more active from late than from early endosomes, probably because of their slightly more acidic pH. Only the A chain of the toxin was found to escape from either 125I-DT/CEM or 125I-transferrin-DT/BW endosomes. Translocation of control endosome labels (125I-transferrin and 125I-horseradish peroxidase) was never observed. We also show that DT receptors present on resistant (mouse) cells block the translocation of the toxin and are responsible for the resistance of these cells to DT. PMID- 1597481 TI - The epsilon-globin gene silencer. Characterization by in vitro transcription. AB - K562 human erythroleukemia cells constitutively express epsilon- and gamma- but not beta-globin genes. We have previously shown that the differential expression of globin genes observed in intact K562 cells could be simulated in vitro as K562 nuclear extract (NE) actively transcribes the epsilon-globin (with 2 kilobases of 5'-flanking sequence) and gamma-globin gene DNA templates but not beta-globin gene templates. We have now used the K562 in vitro transcription system to examine a silencer transcriptional control element which has been reported to be localized between -177 and -392 base pairs (bp) 5' of the canonical cap site for the epsilon-globin gene. We find that K562 NE has markedly reduced synthesis of RNA in vitro from epsilon-globin gene DNA deletion templates which contain the silencer sequence, or part thereof, but not the adjacent 5'-positive regulatory region (-453 to -535 bp). Furthermore, those transcripts generated in vitro from DNA templates extending to -453 bp or less of the epsilon-globin gene were not correctly initiated at the canonical cap site. Separating the K562 NE by ion exchange chromatography, we isolated a fraction (F175) transcriptionally active for all tested globin genes including the epsilon-globin gene containing the silencer sequence and a fraction (F50) which contains the trans-acting factors associated with the silencer activity. F50 showed a strong dose-dependent inhibitory effect on correctly initiated epsilon-globin gene transcription directed by either unfractionated K562 NE or F175. This suppression by F50 was not observed on transcriptional activity of the permissive adenovirus 2 major late promoter. In electrophoretic mobility shift assays using the epsilon-globin gene silencer region as probe, F50 and F175 exhibited different DNA binding protein patterns; a specific protein band in F50 appears to be associated with the silencer activity. These studies suggest that this protein may be specifically responsible for the activity of the silencer element of the epsilon globin gene. The expression and silencing of the epsilon-globin gene during development may be modulated by the interactions of this protein with the cis acting DNA silencer. PMID- 1597482 TI - Kinetic analysis of yeast TFIID-TATA box complex formation suggests a multi-step pathway. AB - The eukaryotic transcription factor TFIID recognizes and binds a promoter sequence element called the TATA box. We have analyzed the interaction of yeast TFIID with the consensus TATA box sequence of the adenovirus major late promoter. To facilitate this detailed characterization, we developed a method for obtaining quantitative information from a gel retardation (bandshift) assay, allowing measurement of the rate and extent of TFIID-TATA box complex formation. Using this assay and DNase I protection assays, we determined that the association rate constant for TFIID binding to the major late promoter was too low to be consistent with a simple diffusion-limited association, suggesting that the binding proceeds by a multi-step pathway. Furthermore, we found that the slow rate of TFIID binding reported by other research groups was not the consequence of a rate-limiting conformational change, as has been previously suggested. Instead, we observed that the formation of a stable TFIID-TATA box complex was relatively rapid (complete in less than 1 min) at saturating concentrations of TFIID. We have proposed a two-step pathway consistent with the observed kinetics and have considered the possible contributions of each step to the overall rate of TFIID binding. This study lays the groundwork for a systematic characterization of the interaction of TFIID with additional TATA box sequences, including an experimental test of the possibility that different steps in the binding reaction are rate-limiting for different promoters. PMID- 1597483 TI - Endocytosis of different members of the small chondroitin/dermatan sulfate proteoglycan family. AB - The family of small interstitial chondroitin/dermatan sulfate proteoglycans consists of at least three different molecular species: biglycan (proteoglycan I), decorin (proteoglycan II), and proteoglycan-100, which has a glycosylated core protein of about 100 kDa. The core protein of decorin has been shown to be responsible for receptor-mediated endocytosis of this proteoglycan species by a variety of mesenchymal cells. It is now demonstrated that skin fibroblasts and articular chondrocytes endocytose biglycan with an efficiency similar to that of decorin. Uptake of biglycan is also mediated by its core protein and can be inhibited by decorin in a partially competitive manner. In human fibroblasts, endosomal proteins of 51 and 26 kDa, which are known to bind decorin core protein, also interact with biglycan. This interaction can be inhibited by decorin. Bovine articular chondrocytes contained binding proteins of 48 and 25 kDa. Proteoglycan-100 can be distinguished from biglycan and decorin by its low clearance rate, which however, exceeds the rate of fluid phase endocytosis. PMID- 1597484 TI - Reversible denaturation of disulfide-reduced ovalbumin and its reoxidation generating the native cystine cross-link. AB - The authors in a previous report (Klausner, R. D., Kempf, C., Weinstein, J. N., Blumenthal, R., and van Renswoude, J. (1983) Biochem. J. 212, 801-810) have argued that native folding of ovalbumin occurs during translation, but not in a renaturation system of the denatured form. To re-examine the possibility, we searched for the conditions of correct oxidative refolding of denatured disulfide reduced ovalbumin. Data of trypsin resistance, CD-spectrum, and selective reactivity of cysteine sulfhydryls revealed that the fully denatured protein can refold into the native conformation under disulfide-reduced conditions. The interconversion between the native and denatured forms was fully reversible with a free energy change for unfolding of 6.6 kcal/mol at 25 degrees C. Subsequent reoxidation under a variety of redox conditions generated only one disulfide bond in the reduced refolded protein with six cysteine sulfhydryls. Furthermore, the regenerated disulfide was found by peptide analyses to correspond to the native disulfide pairing, Cys73-Cys120. We, therefore, concluded that co-translational folding, if any, is not requisite for the correct oxidative folding of ovalbumin. PMID- 1597485 TI - Hormonal regulation of messenger ribonucleic acid encoding a novel isoform of prostaglandin endoperoxide H synthase in rat preovulatory follicles. Induction in vivo and in vitro. AB - Recent purification and amino-terminal analysis of the isoform of prostaglandin endoperoxide H synthase (PGS) induced in rat preovulatory follicles by gonadotropins identified it as a novel distinct isoform of PGS (rPGSi) which exhibited a high degree of homology to the deduced sequence of PGS-related cDNAs recently cloned in chicken and mice. To further verify the similarities of these novel gene products and to examine the hormonal regulation of rPGSi mRNA in ovarian cells, three different in vivo and in vitro models were used. Northern blots using a cDNA encoding the mouse homologue of rPGSi detected a 4.4-kilobase transcript which was rapidly but transiently induced in granulosa cells of preovulatory follicles exposed in vivo to an ovulatory dose of human chorionic gonadotropin. The rPGSi mRNA was undetectable at 0 h, peaked 4 h after human chorionic gonadotropin, and had almost disappeared by 6 h. Increases in rPGSi protein (immunoblots) lagged by about 1 h, peaked at 5 h, and remained present at 11 h. PGSi mRNA and protein were also induced in a time- and dose-dependent manner when preovulatory follicles were isolated and incubated with elevated levels of follicle-stimulating hormone (500 ng/ml) or luteinizing hormone (500 ng/ml), or when differentiated granulosa cell cultures were stimulated with follicle-stimulating hormone, luteinizing hormone, or with gonadotropin-releasing hormone (10(-6) M). In both in vitro systems, rPGSi mRNA peaked at 4-5 h. When the same RNA samples were probed with the mouse cDNA encoding the other PGS isoform, no mRNA transcripts (2.8 kilobases) were observed. These results show for the first time that a rapid and transient induction of mRNA encoding a novel PGS enzyme occurs in granulosa cells of preovulatory follicles prior to ovulation and that results in vitro closely mimicked those in vivo and thereby provide models for studying the molecular mechanisms of rPGSi gene expression. PMID- 1597486 TI - 1,25-Dihydroxyvitamin D3 represses tropoelastin expression by a posttranscriptional mechanism. AB - Tropoelastin expression is down-regulated by exposure to 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), and we present data indicating that this repression is primarily controlled by a posttranscriptional mechanism. Steady-state and functional levels of tropoelastin mRNA were coordinately repressed by 10(-7) M 1,25 (OH)2D3 in fetal bovine chondrocytes, but transcription, as determined by nuclear runoff assay, was not appreciably influenced in fetal bovine chondrocytes or in rat lung fibroblasts. Similarly, exposure to 1,25(OH)2D3 did not influence chloramphenicol acetyl-transferase activity expressed by a human tropoelastin promoter-expression construct in either cell type. Exposure to cycloheximide had little effect on tropoelastin mRNA levels in control cells but partially restored tropoelastin mRNA levels in cells pretreated with 1,25(OH)2D3 and prevented repression when added together with 1,25(OH)2D3. Similarly, simultaneous exposure to actinomycin D and 1,25(OH)2D3 attenuated the down-regulation of tropoelastin. These data indicate that repression of tropoelastin steady-state mRNA levels by 1,25(OH)2D3 is primarily mediated by a posttranscriptional mechanism that requires both transcription and protein synthesis for full effect. PMID- 1597487 TI - Discovery of bone gamma-carboxyglutamic acid protein in mineralized scales. The abundance and structure of Lepomis macrochirus bone gamma-carboxyglutamic acid protein. AB - The mineralized scale of the freshwater sunfish Lepomis macrochirus (bluegill) contains a Gla protein. The protein was identified in extracts of scale by a new colorimetric assay for Gla-containing proteins. The protein was purified by gel filtration chromatography followed by reversed phase high performance liquid chromatography (HPLC). Several tests establish the identity of scale Gla protein and bone Gla protein (BGP). First, the proteins exhibit identical mobilities on electrophoresis and by reversed phase HPLC. Second, they have identical amino terminal amino acid sequences. Finally, identical peptides are generated by proteolytic digestion. The 45-residue amino acid sequence of the bone Gla protein from L. macrochirus has a high sequence homology with swordfish, as well as homology to mammalian bone Gla protein. The BGP of bluegill shares with swordfish BGP a truncated NH2 terminus and an extended COOH terminus. These features may be unique to fish, as they have not been observed in terrestrial vertebrates. The bluegill BGP is the first vitamin K-dependent protein to contain a non-gamma carboxylated residue to the NH2-terminal side of all of its Gla residues. In all other vitamin K-dependent proteins, Gla always appears to the NH2-terminal side of the first Glu. The implications of this result are discussed. The bluegill rib bone is curiously enriched in BGP, as are other mineralized tissues of this species. One hypothesis is that this may be due to the acellular nature of the bone in this species. The abundance of BGP in the bones of this fish may provide clues to the unknown function of this bone protein. PMID- 1597488 TI - Brefeldin A-resistant mutants of human epidermoid carcinoma cell line with structural changes of the Golgi apparatus. AB - We have isolated brefeldin A (BFA)-resistant cell lines, KB/BF-1 and KB/BF-2, from the human epidermoid carcinoma KB cell line. The BFA-resistant phenotypes have been stably maintained for more than 3 months in the absence of BFA. KB/BF-1 and KB/BF-2 showed 10-30-fold higher resistance to cytotoxicity of BFA but were 2 3-fold more sensitive to monensin and nigericin, than KB cells. KB/BF-1 showed aberrant structures of the Golgi complex with poorly developed cisternae surrounded by many small vesicles. Immunocytochemical studies were done with antibodies against a Golgi-specific antigen (chronic rheumatoid arthritis antigen) and a coatomer subunit (beta-subunit for coat proteins of non-clathrin coated vesicles). Golgi-specific markers were distributed into the small vesicles which were localized diffusedly in cytoplasm of KB/BF-1 cells. Such Golgi markers were observed in a strictly confined perinuclear region of the parental KB cells, whereas in the mutant cells the markers were distributed more diffusedly in dot like structures at perinuclear regions. In addition, when exposed to BFA, the mutant and parental cells showed a different distribution of these markers. Synthesis and maturation of low density lipoprotein receptor showed apparently slower rates in processing of low density lipoprotein receptor in KB/BF-1 and KB/BF-2 cells than those observed in their parental KB cells. Protein secretion in KB/BF-1 and KB/BF-2 cells was about 30% less than that in KB cells. Much less inhibition by BFA on the secretion was observed in KB/BF-1 and KB/BF-2 cells. A BFA-resistant mutation in BFA-resistant KB cell lines appears to affect assembly of the Golgi apparatus as well as some Golgi-specific functions. PMID- 1597489 TI - Antiphospholipid syndrome: the reality and implications. AB - A case is made for the existence of a primary antiphospholipid antibody syndrome. This clinical entity can be characterized as including an elevation in titers of antibodies to negatively charged phospholipids, hypercoagulation, thrombocytopenia, and recurrent fetal loss. With further elucidation, the systemic pathologic roles of antiphospholipid antibodies should emerge. PMID- 1597490 TI - The health care crisis and the mean streets of Los Angeles. PMID- 1597491 TI - Management decisions in lone atrial fibrillation. PMID- 1597492 TI - Acute dyspnea in a woman with a chronic pleural mass. PMID- 1597493 TI - Can physicians help curb adolescent violence? AB - Some of the factors associated with such violence, notably racism and poverty, clearly demand societal solutions. Other factors, however, may respond to public health intervention strategies. Emergency room workers can practice secondary intervention, as they do with victims of child abuse, sexual assault, or attempted suicide. Family physicians can refer adolescents for appropriate help. PMID- 1597494 TI - Thoracic adenopathy: metastatic seminoma or sarcoid? PMID- 1597495 TI - A case for narrative. PMID- 1597496 TI - Lithocholic acid accumulation. PMID- 1597498 TI - Extreme ST elevation: ischemia or infarction? PMID- 1597497 TI - Hello, Dollo! PMID- 1597499 TI - Dining out. PMID- 1597500 TI - Allergic fungal sinusitis: an underdiagnosed problem. PMID- 1597501 TI - Beware the semidepressed. PMID- 1597502 TI - Detection of simian immunodeficiency virus RNA from infected rhesus macaques by the polymerase chain reaction. AB - A rapid method for the detection of simian immunodeficiency virus (SIV) RNA from peripheral blood mononuclear cells (PBMC) of experimentally infected rhesus macaques by the polymerase chain reaction (PCR) is reported. The PCR was carried out with a complementary DNA (cDNA) template using 3 pairs of primers that were designed to anneal to homologous sequences in conserved regions of 3 molecular clones of SIVmac. The specificity of the primers was confirmed by performing the PCR with template DNA from the 3 molecular clones. SIV-specific RNA was detected from 30 and 50 infected PBMC/6.25 x 10(5) PBMC of two animals. PMID- 1597503 TI - Detection of cauliflower mosaic virus (CaMV) in single aphids by the polymerase chain reaction (PCR). AB - The detection for the first time of a plant virus in a single aphid by the high sensitivity polymerase chain reaction (PCR) technology is reported. The application of PCR for the detection of viruses in their vectors will aid the understanding of the complex virus-vector relationship and therefore allow the development of new approaches for control of spread of plant virus diseases. PMID- 1597504 TI - A lymphocyte transformation assay for the diagnosis of congenital rubella. AB - A rubella-specific lymphocyte transformation assay, using cryopreserved mononuclear cells, has been developed and used to evaluate specific responses among 21 children with congenitally acquired rubella (CAR), 25 healthy control children and 10 children with sensorineural deafness of unknown aetiology. Although all 21 children with CAR were seropositive, 12 (57.1%) failed to respond to rubella antigen in the transformation assay. Negative in vitro lymphocyte transformation responses were detected significantly more frequently among congenitally infected children below 3 years of age. Thirteen of the 25 (52%) control children were seropositive; only one of these seropositive children (7.6%) gave a negative transformation response. A negative rubella-specific lymphocyte transformation response in a seropositive child, particularly when aged 3 years or younger, is therefore suggestive of CAR. Four of the 10 children with deafness of unknown aetiology were rubella seropositive but gave negative responses in the transformation assay, suggesting that these children had CAR. Our assay may provide a very useful test for retrospective diagnosis of CAR, particularly in children under the age of 3. PMID- 1597505 TI - A modified alkaline phosphatase enzyme amplification system and its application in an HIV antigen ELISA. AB - Alkaline phosphatase amplification systems increase the sensitivity of enzyme linked immunoassays (ELISAs). Here we describe a modified method by which levamisole is a component of the substrate buffer. This increases sensitivity by reducing the signal from non-specific alkaline phosphatases. The modified procedure was applied to an 'in house' HIV-1 p24 antigen capture assay and was shown to increase the sensitivity 4-fold as compared to the unmodified system. The performance of the modified amplification system is comparable to that of commercially available systems. PMID- 1597506 TI - Estimating viral concentrations from dilution counts: an improved HP48SX version of the 'MLE2' program. AB - The recent withdrawal of the HP41C* calculator from the market necessitated a translation of the HP41C* 'MLE2' program published earlier (Roussel and Husson, 1991) into a version for its successor, the HP48SX. The existence of the HP41CV emulator module for the HP48SX offers no solution for continued support of the 'MLE2' program, because it does not accept synthetic HP41C instructions (cf. 'Warning' paragraph in (Roussel and Husson, 1991)). Moreover, the built-in HP48SX upper-tail probability functions (UTPC UTPF UTPN) are more accurate than the corresponding HP41C subprograms. The easy interfacing capabilities of the HP48SX with PC or Macintosh make transfer of the program itself, and its output (e.g. for reporting) straight-forward. This calls for a specific HP48SX implementation with ASCII text output of the algorithm presented by Roberts and Coote (1965), and extended by Roussel and Husson (1991). Finally, the probability distribution of the particle concentration lambda as a function of a given set of counts is shown to be chi 2, so that exact confidence bounds for lambda can be computed using the HP48SX UTPC and ROOT commands. PMID- 1597507 TI - Assessment of concentrations of beet necrotic yellow vein virus by enzyme-linked immunosorbent assay. AB - A quantitative screening method based on enzyme-linked immunosorbent assay (ELISA) was developed for beet necrotic yellow vein virus (BNYVV). With respect to the assessment of the dose-response curve, the response-error relation, and the precision profile the choice of concentrations and replications per concentration was investigated. Special attention was given to control and fulfillment of validity assumptions as formulated by Finney (1978). To this end the influence of the dilution medium for the plant samples on extinction, and on parallelism of standard calibration curves with dilution series of plant samples was studied. The homogeneity of the plates was also explored. Finally the need for transformation of the data before analysis was considered. PMID- 1597508 TI - Comparison of centrifugation methods for molecular and morphological analysis of membranes associated with RNA replication of the flavivirus Kunjin. AB - Kunjin virus-infected cells were lysed and the cytoplasmic extract was subjected to sedimentation analysis. After centrifugation at 16,000 x g for 10 min about 70% of the original RNA-dependent RNA polymerase (RDRP) was recovered in the pellet; most of this enzymic activity was recovered in the soluble fraction after treatment with NP40 detergent. Membrane fractions were prepared from cytoplasmic extracts by centrifugation in discontinuous density gradients comprising w/w or w/v sucrose solutions, either for 3 h (top-loaded on 4 ml 20-60% sucrose) or for 19 h (centre-loaded in 37 ml 0-60% sucrose). Similar separations of bands of light membranes were obtained in all gradients. Multi-layered heavy membrane bands obtained with w/w sucrose gradients were resolved into two well-separated bands (F4 and F5) using w/v sucrose gradients. Thin-section electron microscopy of embedded membrane fractions, gel analysis of intracellular RNA, and RDRP assays showed that the w/w centre loading method and the w/v top-loading (short spin) method produced similar recoveries and distributions of smooth and rough membranes, intact virus particles and RDRP activity. The distribution of intracellular viral RNA and proteins was coincident with the RDRP, all being located in the F4 and F5 bands which contained the characteristic membrane structures induced during flavivirus infection. Significant advantages of the preferred method (w/v sucrose, top loading and short spin) were its rapidity, good preservation of membranes and RDRP, and the concentrations of RDRP achieved in the small volume fractions collected from a total of 4.5 ml. PMID- 1597509 TI - A simple method for the extraction of baculovirus DNA. AB - We have developed a method using lysozyme for DNA extraction from Baculoviruses using as a model Lymantria dispar nuclear polyhedrosis virus (LdNPV) obtained from infected larvae. This method proved to be quick, inexpensive and the extracted DNA was successfully used in molecular hybridization experiments. PMID- 1597510 TI - Mutant actin: a dead end? PMID- 1597512 TI - Muscle filament lattices and stretch-activation: the match-mismatch model reassessed. AB - A mechanism for the observed enhanced stretch-activation phenomenon in insect asynchronous flight muscles has been postulated and developed in terms of the matched helical structures of the actin and myosin filaments in the asynchronous flight muscles of Lethocerus. It was suggested that at different sarcomere lengths with different filament overlaps there would be a changing probability of myosin crossbridge attachment to actin according to whether there was match or mismatch between the myosin and actin arrays. Evidence is provided here that, when Lethocerus structure is considered in detail, the explanation appears to fail. Results on other insect asynchronous flight muscles of different structure (e.g. Apis) also seem to contradict the match-mismatch model. All striated muscle types considered here (fish, frog, Lethocerus, Apis, blowfly) appear to be designed to give constant probability of crossbridge attachment to actin as the filaments move axially, apart from the well-known effects of changing total filament overlap. Alternative stretch-activation mechanisms are considered, especially in terms of the unusual thin filament regulatory system in some insect asynchronous flight muscles. PMID- 1597511 TI - Location of paramyosin in relation to the subfilaments within the thick filaments of scallop striated muscle. AB - Myosin co-assembles with paramyosin in the thick filaments of invertebrate muscles. The molar ratio of the two proteins varies greatly but where sufficient paramyosin is present it forms the filament core with myosin arranged on its surface. In the fastest acting striated muscles, paramyosin is present in small amounts, and neither its location nor the nature of its interactions with myosin has previously been established. Antibodies to paramyosin have now been used in an attempt to locate the protein in thick filaments that have been isolated from the striated adductor muscle of the scallop and then frayed apart into their constituent subfilaments. Using a gold-conjugated secondary antibody, the location of paramyosin in relation to the subfilaments has been determined by electron microscopy of negatively stained samples. The labelling indicates that paramyosin extends throughout the length of the scallop filaments and appears to be associated with each subfilament, raising the possibility that in these filaments paramyosin may not be confined to a central core domain. PMID- 1597513 TI - Limits to shortening in smooth muscle tissues. AB - The extent of shortening in smooth muscle tissues is limited by a number of internal and external factors. In this study, continuous measurements of the stiffness of active muscle were made to characterize the mechanical forces acting to limit shortening. Rabbit ovarian ligament and mesotubarium superius muscles were allowed to shorten as far as possible under light afterloads; under these conditions a stiffness increase was observed that was closely related to the instantaneous muscle length and that was unaffected by other factors influencing the degree of shortening (afterload, time and intensity of activation, temperature, etc.). The results are considered in terms of a hypothesis relating the tissue-based constraints on radial expansion at short lengths to an additional load on the contractile apparatus, an internal force that is externally manifested as an increase in axial stiffness. Changing the cellular volume by varying the tonicity of the bathing medium provided tentative confirmation of the hypothesis. PMID- 1597515 TI - Low dose radiation and childhood cancer. PMID- 1597514 TI - Effects of ethylene glycol on the kinetics of contraction on flash photolysis of caged ATP in rat psoas muscle fibres. AB - ATP (1-1.2 mM) was photoreleased from caged ATP (5 mM) in skinned fibres from rat psoas muscle at 15-17 degrees C, to examine the effects of ethylene glycol (EG; 20% in solvent) on the kinetics of isometric contraction. Muscle fibres were stretched by 0.5-2% before photolysis, so that force just before photolysis was almost equal to the steady-state force after photolysis. At the phase of steady state contraction, force and 500 Hz-stiffness in the presence of EG were 50% and 70% of the controls, respectively, resulting in a higher stiffness-to-force with EG, as reported previously. Following photolysis, force fell before rising to a steady-state plateau. The estimated rate constant of the force decay was approximately 90 s-1, and in the presence of EG was 80-85% of the control. This suggested a small effect of EG on the crossbridge detachment induced by ATP. The rate of force redevelopment was approximately 70 s-1, and EG decreased this rate to 50% of the control. This suggested that EG greatly slows the transition of the crossbridges from the detached state to the reattached force-producing state. The time course of the stiffness signals was consistent with this interpretation. The high stiffness-to-force ratio with EG indicated that EG not only reduces the rate constants which were directly examined in this study but also modifies other aspects of the crossbridge reaction. PMID- 1597516 TI - Contribution of fine needle aspiration cytology to diagnosis and management of thyroid disease. AB - AIMS: To determine the role of fine needle aspiration cytology (FNAC) in the diagnosis and management of thyroid disease. METHODS: Clinical histories of 144 patients who had undergone FNAC of the thyroid were analysed. Clinical presentation, non-invasive investigations including hormone assays, ultrasound, and isotope scan procedures were compared with FNAC diagnoses in all cases and with histological diagnosis in the 28 cases (19%) that had undergone surgery. Clinical management was decided upon combining all of the above investigations. The relative contribution of the FNAC was divided into: essential, additional and non-contributory, misleading. RESULTS: FNAC diagnoses included: 29 (16%) benign colloid goitre, 56 (39%) benign cystic goitre, 24 (17%) thyroiditis, and 22 (15%) neoplasms. Nineteen (13%) of the specimens were unsatisfactory. When compared with clinical diagnoses based on non-invasive diagnostic investigations FNAC represented no improvement on the diagnosis of benign colloid/cystic goitre (55% v 54% respectively). It represented an improvement on the diagnosis of thyroiditis (9% v 17% respectively). FNAC decreased clinically suspicious lesions in which 22 neoplasms were diagnosed from 37% to 15%. Eleven patients with neoplasms underwent surgery and neoplasms were confirmed histologically. Others including lymphoma, metastatic carcinoma, and analplastic carcinoma were managed conservatively. There were four false negative FNAC diagnoses (3%) in clinically suspicious lesions, found on histology to be benign follicular adenomas. CONCLUSIONS: FNAC had an essential role in the diagnosis and management of 23% of our patients, a confirmatory role in 61% of patients, a non-contributory role in 13% when specimens were inadequate, and was misleading in 3% where results were false negative. The positive identification of thyroiditis and neoplasia stands on its own as a justification for FNAC. PMID- 1597518 TI - Serum myoglobin and creatine kinase enzymes in acute myocardial infarction treated with Anistreplase. AB - AIMS: To compare plasma myoglobin concentration and cardiac enzyme activity with electrocardiographic (ECG) changes in two groups of patients (reperfused and non reperfused) participating in a placebo-controlled randomised double blind trial of treatment of myocardial infarction (MI) with intravenous thrombolytic therapy (Anistreplase). METHODS: Twenty two patients with confirmed MI obeying strict inclusion and exclusion criteria were studied. Plasma myoglobin was measured by radioimmunoassay and creatine kinase enzyme (CK and CKMB) by NAC activated and NAC activated/immunoinhibition methods respectively in all patients before and at frequent intervals after injection of Anistreplase or placebo. Patients were divided into reperfused (R) and non-reperfused (NR) groups on the basis of ECG criteria. Reperfusion was diagnosed if the measured ST segment elevation fell by greater than or equal to 50% at 2 hours post dosing. RESULTS: The time to peak (TTP) myoglobin was significantly less in the R group compared with the NR group but there was considerable overlap in the range of values. The area under the enzyme time curves (AUCs) and summed ST segment epsilon ST elevations were significantly smaller in the R compared with the NR group. CONCLUSIONS: Although TTP myoglobin results were significantly lower in the R group, TTP myoglobin will probably not be useful as an non-invasive indicator of reperfusion because of the overlap in values between the two groups. The significant reduction in the AUC and epsilon ST only in the R group suggests decreased infarct size. However, in this small preliminary study reperfusion did not occur more frequently with Anistreplase than without. PMID- 1597517 TI - Immunophenotype of multinucleated and mononuclear cells in giant cell lesions of bone and soft tissue. AB - AIMS: To compare the antigenic phenotype of giant cells in giant cell lesions of bone and soft tissue with that of osteoclasts and macrophage polykaryons. METHODS: Formalin fixed, paraffin wax embedded sections of 106 giant cell lesions, 19 granulomatous, and 14 osteoclast containing lesions were immuno histochemically stained for leucocyte common antigen (LCA), CD68, and HLA-DR. RESULTS: Osteoclasts and giant cells of giant cell tumour of bone and giant cell reparative granuloma could be distinguished by their generalised absence of HLA DR reaction from macrophage polykaryons and giant cells in other giant cell lesions of bone and soft tissue. Staining for LCA, CD68, and HLA-DR was useful in distinguishing reactive histiocytic giant cells and osteoclasts from tumour giant cells. CONCLUSIONS: A panel of macrophage associated antigens should be diagnostically useful in differentiating the histological nature of giant cells in various giant cell lesions of bone and soft tissue. PMID- 1597519 TI - Localisation of intrahepatic interleukin 6 in patients with acute and chronic liver disease. AB - AIM: To evaluate the role of local interleukin 6 (IL-6) in the pathogenesis of acute and chronic liver disease. METHODS: The cellular site of IL-6 in cryostat sections of liver from 31 patients with liver disease was examined using indirect immunofluorescence with a monoclonal antibody. RESULTS: IL-6 staining in sinusoidal endothelial cells was very noticeable and diffusely distributed in the lobules of specimens of acute viral hepatitis. IL-6 expression in endothelial cells, particularly in necrotic areas of hepatocytes, was increased and was accompanied by enhanced expression in Kupffer cells. In contrast, IL-6 staining in infiltrating mononuclear cells was prominent in portal tracts, and the numbers of cytokine positive cells were greater in specimens of chronic active hepatitis compared with chronic persistent hepatitis. In non-specific reactive hepatitis intrahepatic expression of IL-6 was minimal, while in alcoholic liver fibrosis the cytokine distribution in the lobules was similar to that of acute viral hepatitis. CONCLUSIONS: These results indicate that locally produced IL-6 contributes to the inflammatory process and immunological response in acute and chronic liver disease. PMID- 1597520 TI - Rapid method for detecting monoclonality in B cell lymphoma in lymph node aspirates using the polymerase chain reaction. AB - AIMS: To use the polymerase chain reaction to detect monoclonality at the immunoglobulin heavy chain gene locus in cells derived from lymph node aspirates. METHODS: A nested two-stage polymerase chain reaction (PCR) for the VDJ region of the immunoglobulin heavy chain gene was used to detect monoclonality. The total number of cells available for diagnosis by PCR in lymph node aspirates was between 10(4) and 10(5). RESULTS: A monoclonal band was detected in 21 of 25 malignant B-lymphomas. The other four specimens gave polyclonal bands. Specimens from reactive lymph nodes produced polyclonal bands in 14 cases, no product in two cases, and one specimen gave two monoclonal bands. Polyclonal bands were obtained for three Hodgkin's lymphoma samples and five metastatic carcinomas. Four metastatic carcinoma samples gave no amplification. CONCLUSIONS: Detection of monoclonality in a cell population is strongly suggestive of malignant disease. The simple PCR method presented here should complement conventional cytological and immunological methods for diagnosis of malignancy by lymph node aspirates. PMID- 1597521 TI - Detection of bone marrow metastases in neuroblastoma using a short term tissue culture technique. AB - AIMS: To improve detection of neuroblastoma metastases in the bone marrow: morphological evaluation of bone marrow is a routine and important component of the clinical staging of neuroblastoma and it depends on the successful identification of tumour cells which may only be present at extremely low levels. METHODS: Bone marrow mononuclear cells from patients with neuroblastoma were incubated in a simple suspension culture and examined regularly using an inverted objective microscope. In some cases cytospins of the cultured cells were examined further using morphological and immunocytological techniques. RESULTS: In some cultures spheroidal clumps of cells could be seen growing after only a few days. If the marrow was cultured for a longer period these spheroids continued to increase in size, became adherent to the stromal cell layer on the culture flask floor, and put out long characteristic processes (neurites). Morphological and immunocytological examination of cytospins from these cultures confirmed these cells as neuroblasts. CONCLUSIONS: This method has provided the sole evidence of marrow metastases in several newly diagnosed cases of neuroblastoma in which the bone marrow had shown no evidence of tumour using standard morphological and fluorescent immunocytological techniques. Although negative cultures do not preclude the presence of neuroblastoma, this method is a useful adjunct to the standard techniques. PMID- 1597522 TI - Development of acute leukaemia after idiopathic myelofibrosis. AB - AIMS: To determine the characteristics of blastic transformation of idiopathic myelofibrosis. METHODS: The clinical and haematological features, as well as the morphological characteristics of blast cells, were analysed in nine adults with blast transformation. RESULTS: Most of the patients were male and had enlarged spleens and livers. Five of the patients had normal platelet counts, while all had pronounced anaemia and a moderate degree of leucocytosis. The duration of the acute phase was usually short: 16 (SD 8) weeks. Most myeloid cell lineages- granulocytic, monocytic, and megakaryocytic--were similarly distributed. One patient also had a hybrid (lymphoid-myeloid) phenotype. The morphological assessment of blast cells agreed with immunophenotyping in five out of the nine cases. The onset of the blastic phase was not related to previous treatment. CONCLUSIONS: A pluripotential stem cell with preferential myeloid commitment would be the target cell of blast transformation in idiopathic myelofibrosis. Our immunophenotypic data do not support the concept of a preferential association between megakaryocytic lineage and the acute transformation of idiopathic myelofibrosis. The absence of previous treatment in some cases suggests that this kind of evolution is part of the natural history of idiopathic myelofibrosis. PMID- 1597523 TI - Autoimmune neutropenia of infancy. AB - AIM: Assessment of the clinical and haematological course of autoimmune neutropenia of infancy (ANI) in a defined childhood population in the south east of Scotland. METHODS: From January 1986 to February 1991 all children presenting with persistent neutropenia were examined serologically for evidence of antigranulocyte antibodies. The clinical course of those children found to have anti-granulocyte antibodies was then closely monitored. RESULTS: During the study period five children had serologically confirmed ANI, giving an annual incidence of approximately 1/100,000 in this population. All of these cases followed the classic benign course of the condition. The presenting illnesses were mild, often with superficial skin sepsis and the initial absolute neutrophil count (ANC) ranged from 0.00-0.87 x 10(9)/l. All have remained well with no serious infections. Two children attained a normal ANC after 14 and 24 months respectively, the others currently remain neutropenic. CONCLUSIONS: Autoimmune neutropenia of infancy is a condition which rests on a serological diagnosis. It follows a chronic benign course and all children eventually attain a normal ANC. The level of antigranulocyte antibody in the serum often begins to wane prior to improvement in the ANC and can give an indication of when recovery will begin to occur. PMID- 1597524 TI - Evaluation of five commercial assays for screening antenatal sera for antibodies to Toxoplasma gondii. AB - AIMS: To evaluate the suitability of five commercial assays (Toxoreagent, DA, Captia Toxo IgG, Toxenz-G, Toxonostika-G) for screening large numbers of sera for antibodies to Toxoplasma gondii. METHODS: Sera from 1000 pregnant women booking for antenatal care at a London hospital were screened in parallel by each test. Sera giving discordant results were retested. RESULTS: The Captia Toxo IgG enzyme immune assay gave the best specificity on initial screening, with 0/773 false positives and only 2/218 false negatives. The Toxoreagent latex agglutination test performed well provided sera were tested at several dilutions to prevent prozone effects; 0/218 false negatives (greater than 12 IU/ml). Only one evidently false positive result was seen in the 1000 samples tested. The DA test gave no false negative results but produced 23/773 false positives. After repeat testing there were 9/1000 sera which gave equivocal results which were negative by the Captia Toxo IgG test (less than 12 IU/ml) but with low titres of 16 in the Toxoreagent test or 4 IU/ml in the DA test. In this situation women would have been asked for a follow up sample for repeat testing. Only 300 sera were tested by Toxenz-G; initial screening produced 4/58 false negative results and 4/242 false positives. CONCLUSIONS: The Captia Toxo IgG test gave the fewest discordant results on initial screening. Results could be readily expressed in international units using a programmable plate reader, and this may be useful for epidemiological studies. The Toxoreagent test is considerably cheaper, and is a simple and reliable method for screening provided that at least two dilutions are used. PMID- 1597525 TI - Polymerase chain reaction for the detection of Neisseria gonorrhoeae in clinical samples. AB - AIMS: To evaluate the use of a cppB gene derived polymerase chain reaction (PCR) assay for direct detection of Neisseria gonorrhoeae in clinical samples. METHODS: A PCR assay was performed on 33 N gonorrhoeae strains and 12 other Neisseria species and other normal genital flora to evaluate the specificity of the chosen cppB primers. The assay was subsequently evaluated with 52 clinical swab samples collected from China. RESULTS: An amplified product of 390 base pairs (bp) was observed with all the N gonorrhoeae strains, each of these products on digestion with the restriction enzyme MspI produced two bands of 250 bp and 140 bp respectively. This set of primers did not produce any amplified product of the expected length with the other non-gonococcal strains tested. For the 52 clinical swabs, 34 were culture positive and PCR successfully detected all these positives. In addition the PCR was positive for two swabs which were culture negative but positive for N gonorrhoeae antigens when tested with the ELISA method (Gonozyme). CONCLUSIONS: This PCR assay is a promising diagnostic tool for detection of gonococci directly from clinical swab samples. Further evaluation is necessary. PMID- 1597526 TI - Multinucleated stromal giant cells in adolescent gynaecomastia. AB - Bizzare multinucleated stromal giant cells were observed in a case of adolescent gynaecomastia. Similar cells have been described in the female breast in both benign and malignant conditions where they are thought to originate either from reactive stromal cells or from the mononuclear phagocyte system, respectively. Immunohistochemistry and electron microscopy in this case support the idea that they originate from stromal fibroblasts. Their occurrence in gynaecomastia is further evidence that these changes in stromal cells may be due to hormonal influences. PMID- 1597527 TI - Ageing and duodenal morphometry. AB - Small bowel morphometry was studied in 25 subjects under the age of 70 years and 22 over the age of 70. There was no evidence of malabsorption or malnutrition in either group. Two distal duodenal endoscopic biopsy specimens were examined morphometrically. There were no significant correlations between age and areas of duodenal surface epithelium, crypts and lamina propria, heights of villi and surface epithelium, depth of crypts, crypt to villus ratio, number of intraepithelial lymphocytes, duodenal architecture, enterocytes, brush border and Brunner glands. Contrary to previous reports there was no evidence for a significant effect of age on proximal small bowel morphometry. PMID- 1597528 TI - Histological audit of acute appendicitis. AB - One hundred retrospective appendectomy specimens were examined in an attempt to study the degree of uniformity and clarity of reporting of this common surgical specimen. There was full agreement in 73 cases and some degree of discrepancy in 27 cases. It is suggested that greater clarity in reporting can be achieved with five reporting categories: (i) established acute inflammation; (ii) no evidence of acute inflammation ("normal"); (iii) features suggestive of early inflammation; (iv) peri-appendicitis; (v) other features, such as granulomata, Enterobius vermicularis, tumours, etc. PMID- 1597529 TI - Current views on CIN. PMID- 1597530 TI - Haemopoietic stem cells and the development of the blood cell repertoire. PMID- 1597531 TI - Association of Ebola-related Reston virus particles and antigen with tissue lesions of monkeys imported to the United States. AB - During 1989-1990, an epizootic involving a filovirus closely related to Ebola virus occurred in a Reston, Virginia, primate-holding facility. Tissues were collected from cynomolgus monkeys and examined by electron microscopy and immunohistochemistry for Ebola-related viral antigen. Viral replication was extensive in fixed tissue macrophages, interstitial fibroblasts of many organs, circulating macrophages and monocytes, and was observed less frequently in vascular endothelial cells, hepatocytes, adrenal cortical cells and renal tubular epithelium. Viral replication was observed infrequently in epithelial cells lining ducts or mucous membranes, intestinal epithelial cells, eosinophils and plasma cells. Replication of Reston virus in lymphocytes was never observed, in contrast to reports of lymphocytes of monkeys experimentally infected with the Ebola-Zaire virus. Free filoviral particles were seen in pulmonary alveoli and renal tubular lumina, which correlates with epidemiological evidence of droplet and fomite transmission. Viral infection of interstitial fibroblasts and macrophages caused multisystemic disruptive lesions involving connective tissue. Focal necrosis in organs where viral replication was minimal may have been secondary to ischaemia caused by fibrin deposition and occasional platelet-fibrin thrombi. Immunoelectron microscopy on sections of liver, differentiated viral tubular inclusion masses and precursor material from non-viral tubuloreticular inclusions. Immunohistochemistry showed that the distribution of viral antigen in affected tissue correlated well with ultrastructural localization of virions. PMID- 1597532 TI - Sero-surveillance for orf antibodies in sheep and goats in Saudi Arabia employing the ELISA technique. AB - A serological survey was conducted on sheep and goats in Saudi Arabia to detect humoral antibodies against the orf virus. The ELISA technique was superior to the AGID and CFT in detecting such antibodies. Of the 239 abattoir serum samples examined, 60 per cent had orf antibodies by ELISA while 94.8 per cent of the convalescent sera had antibodies detectable by ELISA. With the lack of vaccination and the reports that the clinical disease is commonly seen in different parts of the Kingdom, it may be that orf is becoming enzootic in this country. Recommendations for implementing a satisfactory vaccination regimen are given. PMID- 1597533 TI - Experimental reproduction of porcine proliferative enteritis. AB - A campylobacter-like bacterium, isolated from the terminal ileum of a pig with porcine proliferative enteritis (PPE), was used to initiate PPE in healthy crossbred pigs. Post-mortem examinations of pigs infected orally with the bacterium revealed thickening of the terminal ileum, haemorrhage within the ileum, degeneration of ileal villi and large quantities of bile and mucous in the ileal contents. Histopathological examination revealed that the terminal ileum, ileo-caecal valve and caecum from infected pigs had partial or total loss of mucous membrane, hyperplasia of the crypt and glandular epithelial cells, campylobacter-like organisms in and around the Peyers' patches and lymphoid aggregates in the mucosa. The causative organism was re-isolated from the intestinal specimens of infected animals post-mortem. In control animals, kept under the same conditions, no evidence of abnormality was observed in the terminal ileum, ileo-caecal valve or caecum. PMID- 1597534 TI - The histological nature of epulides in dogs. AB - The histological characteristics of a series of 154 oral tumours with the clinical appearance of epulides in 129 dogs were reviewed. Diagnoses were based on current criteria in human oral pathology and compared with the original diagnoses. The histological findings suggested that the majority of epulides in the dog can be classified as focal fibrous hyperplasia (43.5 per cent), peripheral ameloblastoma (17.5 per cent), peripheral odontogenic fibroma (WHO type) (16.9 per cent) and pyogenic granuloma (1.95 per cent). In addition, a number of other odontogenic tumours (1.95 per cent) and non-odontogenic tumours (18.2 per cent) such as fibrosarcoma and squamous cell carcinoma, which are not traditionally associated with the clinical appearance of an epulis, were diagnosed. Of 74 lesions that were previously diagnosed as fibromatous and ossifying epulides, 50 (68 per cent) were reclassified as focal fibrous hyperplasia and 21 (28 per cent) as peripheral odontogenic fibroma (WHO type). The majority of lesions (76 per cent), which were originally classified as acanthomatous epulis, were found to be peripheral ameloblastoma. In addition, three squamous cell carcinomas, two rare odontogenic tumours and two cases of focal fibrous hyperplasia were diagnosed in this classification. It was concluded that, as in man, the term epulis is a clinically descriptive term and that the renal nature of these lesions should be determined histologically. PMID- 1597535 TI - Necrotic colitis associated with Entamoeba histolytica infection in a cat. AB - A 3-year-old Persian cat developed bloody diarrhoea. On histological examination, a marked necrotic colitis with a large number of invading protozoan parasites was observed. The protozoan was identified as Entamoeba histolytica by light and electron microscopy. This is the first report describing spontaneous amoebiasis in cats. PMID- 1597536 TI - A review of the primary dysautonomias of domestic animals. AB - Primary dysautonomias appear to be the result of initial damage to the protein synthetic pathway of a specific neuronal population, but despite detailed morphological study of several species there is, as yet, no indication of the precise lesion or the nature of the causal agent. The very marked similarities between the species with regard to lesion type, distribution, the age group affected and the geographical restrictions of occurrence would suggest a very similar, if not common, aetiology. There is no explanation, however, for the 70 year gap between its appearance in horses and its subsequent occurrence in other species or why it is these species, with very different physiology, habits and habitats, that are affected. No reference could be found in the literature to any infectious agent or toxin causing a similar range of structural effects with a similar species specificity or lesion distribution. Many questions about dysautonomias remain. Why is the lesion distribution so specific? At what level of the synthetic pathway does the primary lesion occur? What are the unusual compounds demonstrated in "acute phase" serum from affected horses; are they a neurotoxic agent(s) and/or its metabolites, or the abnormal product of an affected animal? Why did the experimental ponies which developed autonomic lesions not become ill? When do the clinical signs appear in relation to the occurrence of the primary lesion? Why are adolescent and young adult animals most commonly affected? As the general understanding of neuronal function and the numerous factors which influence it improves, the many subtle distinctions and similarities amongst the myriad sub-populations of neurones will become clearer and common features may emerge which will link the seemingly disparate neuronal types involved in the primary dysautonomias. PMID- 1597537 TI - Geriatric nail disorders: diagnosis and treatment. AB - Age-associated nail changes and disorders are common in elderly patients. Characteristic changes in color, contour, growth, surface, thickness, and histology occur in the nail unit as persons become older. Several onychodystrophies are frequently observed in these elderly patients: brittle nails, those induced by faulty biomechanics and trauma, infections, onychauxis, onychoclavus, onychogryphosis, onychophosis, splinter hemorrhages and subungual hematomas, and subungual exostosis. Awareness of the signs and symptoms of the aging nail will enable better assessment and management of the onychologic concerns of this group of older patients. PMID- 1597538 TI - Effects of topical ammonium lactate on cutaneous atrophy from a potent topical corticosteroid. AB - BACKGROUND: Topical corticosteroids produce atrophic changes in skin, including thinning of the epidermis and decrease in dermal ground substance. We observed that 12% ammonium lactate produced an increase in the thickness of epidermis and increased amounts of dermal glycosaminoglycans. OBJECTIVE: Our purpose was to determine whether 12% ammonium lactate could minimize cutaneous atrophy produced by a potent topical corticosteroid. METHODS: Clobetasol propionate, 12% ammonium lactate, and both agents were repetitively applied under occlusive patches as well as in open patches on the forearms of human volunteers for 3 to 4 weeks. Biopsy specimens were analyzed for thickness of the epidermis and dermal glycosaminoglycans by image analysis. RESULTS: Twelve percent ammonium lactate produced a significant sparing of atrophy in both the epidermis and dermis without any influence on the bioavailability or antiinflammatory properties of the corticosteroid. CONCLUSION: Twelve percent ammonium lactate may be useful in mitigating the adverse effects of corticosteroid on skin. PMID- 1597539 TI - Oxicam-induced photosensitivity. Patch and photopatch testing studies with tenoxicam and piroxicam photoproducts in normal subjects and in piroxicam droxicam photosensitive patients. AB - BACKGROUND: The mechanism of piroxicam-induced photosensitivity is unknown. It was first attributed to metabolites of the drug produced in vivo but further photochemical studies disclosed that piroxicam was not stable to light, forming at least two photoproducts. Photosensitivity reactions to droxicam and tenoxicam have been not reported. OBJECTIVE: The aim of this study was to determine whether piroxicam photoproducts contribute to the light reactions induced by this drug, to describe a case of droxicam-induced photosensitivity and to study the in vivo photosensitizing potential of tenoxicam. METHODS: Patch and photopatch tests with two major photoproducts of piroxicam, with different preparations of UVA preirradiated piroxicam, and with low and high concentrations of tenoxicam were performed in normal volunteers and in piroxicam-photosensitive patients. Phototesting studies were also performed before and after the oral administration of tenoxicam in both groups of subjects. RESULTS: Positive patch test responses were obtained in piroxicam-photosensitive patients only with the preirradiated piroxicam preparations. Phototesting studies with tenoxicam were normal in both groups. CONCLUSION: Minor or intermediate piroxicam photoproducts are more likely to be responsible for the photosensitivity reactions induced by this drug. PMID- 1597540 TI - Obsessive-compulsive disorder in patients with chronic pruritic conditions: case studies and discussion. AB - BACKGROUND: Relatively few persons with obsessive-compulsive disorder (OCD) come to psychiatric clinics for treatment. Our hypothesis was that patients with a form of OCD that involves compulsive hand and body washing might initially seek treatment from a dermatologist. OBJECTIVE: Our purpose was to screen patients attending a dermatology clinic to determine the frequency of OCD cases and to help dermatologists recognize this disorder. METHODS: Randomly selected patients who presented with one of several chronic pruritic conditions were interviewed to determine the presence of anxiety disorders. RESULTS: A significantly high percentage of the patients (14%) were found to have previously undiagnosed OCD. Case studies of five of these patients are presented. CONCLUSION: A significant number of patients with undiagnosed OCD appear to present to dermatology clinics. Identification and referral for psychiatric consultation may aid in the treatment of both OCD and concomitant dermatologic conditions. PMID- 1597541 TI - Widespread cutaneous and systemic calcification (calciphylaxis) in patients with the acquired immunodeficiency syndrome and renal disease. AB - BACKGROUND: Calciphylaxis is a form of widespread calcification that may occur in patients with renal disease and hyperparathyroidism. The skin is often affected secondary to vascular compromise and ischemia. Patients infected with the human immunodeficiency virus (HIV) are predisposed to renal failure and thus may develop this serious complication. OBJECTIVE: The purpose of this article is to describe two cases of fatal calciphylaxis in patients with the acquired immunodeficiency syndrome and renal disease. METHODS: Two patients were examined clinically and through the performance of serologic studies and skin biopsies. RESULTS: Both patients had a widespread livedo reticularis-like eruption, which rapidly progressed to cutaneous gangrene. Patient 1 had elevated serum calcium and phosphorus levels whereas patient 2 had normal values but had markedly elevated serum parathyroid hormone levels. Biopsy specimens in both cases showed vascular thrombosis and soft tissue calcification. CONCLUSION: Widespread calcification may develop in patients with HIV infection and renal failure and, in some cases, calcium and phosphorus levels may be normal. PMID- 1597542 TI - Secondary autoimmune diseases in herpes gestationis (pemphigoid gestationis). AB - BACKGROUND: Herpes gestationis (HG) is an autoimmune disease of the skin that occurs exclusively in association with pregnancy (or trophoblastic disease). It is associated with the HLA-DR3 and -DR4 antigens that are also associated with several other autoimmune diseases. HG has previously been reported in association with Graves' disease. OBJECTIVE: Our purpose was to determine the frequency of other autoimmune disease(s) in patients with a history of HG. METHODS: Seventy five patients with a history of HG were studied for the frequency of other autoimmune diseases. RESULTS: We found an increased frequency of Graves' disease in patients with a history of HG. Those with HG have an increased risk for the development of other autoantibodies. There is an increased frequency of autoimmune diseases in the family members of patients with HG. CONCLUSION: Secondary autoimmune disease in HG is unusual, but does occur. The most frequent is Graves' disease. PMID- 1597543 TI - Drug-induced toxic epidermal necrolysis (Lyell syndrome) in patients infected with the human immunodeficiency virus. AB - BACKGROUND: Although patients infected with the human immunodeficiency virus (HIV) are predisposed to cutaneous adverse drug reactions, only a few cases of toxic epidermal necrolysis (TEN) have been reported in this setting. OBJECTIVE: Our purpose was to examine the features of TEN in HIV-infected patients. METHODS: We performed a retrospective analysis of all HIV-infected patients in a series of 80 consecutive cases of TEN during a 6-year period. RESULTS: Fourteen patients were HIV infected. They had typical TEN, with epidermal detachment involving 20.6% +/- 8.0% of the skin surface. Suspected drugs were sulfadiazine, trimethoprim-sulfamethoxazole, sulfadoxine, clindamycin, phenobarbital, and chlormezanone. Patients with the acquired immunodeficiency syndrome (AIDS) exhibit a dramatically increased risk of TEN. During our study period 15 cases of AIDS-associated TEN occurred in the greater Paris area, whereas 0.04 case would have been expected if the incidence of TEN were the same in these patients as in the general population. CONCLUSION: HIV-infected patients, especially those with AIDS, may develop TEN that shares many similarities with the disease in immunocompetent patients. PMID- 1597544 TI - Cutaneous leukocytoclastic vasculitis associated with active Wegener's granulomatosis. AB - BACKGROUND: Cutaneous manifestations are common in Wegener's granulomatosis and may occur at any time during the illness. OBJECTIVE: Our purpose was to describe the relation of the appearance of cutaneous leukocytoclastic vasculitis to activity and other manifestations of Wegener's granulomatosis. METHODS: Three patients with Wegener's granulomatosis who had recent onset of skin lesions are reported. Data regarding the relation of their cutaneous disease to their systemic disease was collected. RESULTS AND CONCLUSION: In each case, onset of the skin lesions of biopsy-proven cutaneous leukocytoclastic vasculitis was associated with activation of the systemic features of Wegener's granulomatosis. PMID- 1597545 TI - Lack of predictive factors for the clinical course of bullous pemphigoid. AB - BACKGROUND: Bullous pemphigoid is a clinically heterogeneous disease although little is known of the factors affecting its course and outcome. OBJECTIVE: Our purpose was to document the clinical course, outcomes, and causes of death in treated bullous pemphigoid and to determine the predictive factors affecting outcome. METHODS: The clinical course was documented in 82 patients with immunologically proven bullous pemphigoid (mean follow-up 3 years 2 months). To identify factors predictive of outcome, 16 patients with "good prognosis bullous pemphigoid" (no systemic treatment or in remission within 2 years) were compared with 12 patients with recurrent disease requiring maintenance therapy who still needed treatment after 3 years or longer. Remission was defined as 3 months free of lesions, without systemic treatment. RESULTS: The disease duration varied from 9 weeks to 17 years (estimated median treatment time 2 years 1 month). Of patients followed up for at least 2 years, 30% achieved remission and by 3 years the remission rate was 50%. Two patients had a subsequent relapse (9%). The mortality rate at 1 year was 19%, and treatment was believed to be contributory in seven deaths. No clinical, immunologic, or immunogenetic factors were predictive of disease duration. CONCLUSION: Despite the heterogeneity of the clinical course and duration of bullous pemphigoid, no predictive factors are recognized. PMID- 1597546 TI - Epidemiology of isotretinoin exposure during pregnancy. AB - BACKGROUND: Exposure to isotretinoin during pregnancy is associated with a high risk of major fetal malformations. OBJECTIVE: Our purpose was to determine the reasons for and outcomes of in utero isotretinoin exposure. METHODS: On the basis of 433 spontaneous reports, we describe the likely reasons these exposures occurred and the outcomes of these pregnancies. In our analysis of the outcomes of pregnancy, we separately consider the pregnancies known to us before their outcomes were determined as prospective cases. RESULTS: Timing of conception in relation to initiation of therapy with isotretinoin was known for 396 women. Of these, 130 patients (33%) were already pregnant when they started isotretinoin. An additional 65 patients (16%) became pregnant in the first 3 weeks of isotretinoin use. Pregnancy outcomes were known on 409 pregnancies. Among these, 222 (54%) ended in elective abortion and 29 (7%) in spontaneous or missed abortion. Of 151 births, 72 (48%) were normal, 71 (47%) had congenital malformations, and 8 (5%) had abnormalities other than malformations. Of 94 prospectively ascertained pregnancies that ended in births, 28% had congenital malformations (95% confidence interval 19% to 37%). Exposure to isotretinoin during any time and for as little as one capsule within the first trimester have been associated with congenital malformations. CONCLUSION: The high proportion of exposures in already or recently pregnant women illustrates the importance of obtaining a negative pregnancy test before the initiation of isotretinoin therapy and of delaying the commencement of isotretinoin therapy until the onset of the next menstrual period. Furthermore, the importance of reliable contraceptive methods should be emphasized to patients when isotretinoin is prescribed. Young women seem to be at an especially high risk of pregnancy exposure to isotretinoin. There is a substantial risk of congenital malformation at all therapeutic doses of isotretinoin, even when the duration of exposure is brief. PMID- 1597547 TI - Present status of eyelid phototherapy. Clinical efficacy and transmittance of ultraviolet and visible radiation through human eyelids. AB - BACKGROUND: Phototherapy for the eyelid has not previously been recognized as a safe and effective treatment of photoresponsive dermatoses of the eyelid, such as atopic dermatitis, vitiligo, psoriasis, lymphomatoid papulosis, and parapsoriasis. OBJECTIVE: The purpose of this study was to demonstrate the efficacy and safety of this treatment. METHODS: Two cases are presented to demonstrate clinical efficacy. In addition, a retrospective eye evaluation of seven patients receiving a combined total of greater than 1300 eyelid phototherapy treatments was performed. To determine whether potentially harmful UV radiation is significantly transmitted through eyelid skin, an in vitro study was conducted to measure the percentage transmittance of ultraviolet-visible radiation through five excised eyelids. RESULTS: In the two cases presented, remarkable improvement occurred without adverse side effects, suggesting that it is possible to deliver incremental UV dosages to eyelid skin to achieve clearing of skin disease. Retrospective analysis of patients' records revealed no ocular disease from the phototherapy. In vitro eyelid examination produced data that indicated negligible quantities of UV radiation were transmitted through eyelid skin compared with the visible spectrum, in which up to 77% of the radiation was transmitted through the tissue. CONCLUSION: The combined clinical experience and transmittance data suggest that eyelid phototherapy is a safe and effective treatment in selected patients. PMID- 1597548 TI - High-dose hydroxychloroquine treatment of porphyria cutanea tarda. AB - BACKGROUND: High-dose hydroxychloroquine is rarely used in the treatment of porphyria cutanea tarda (PCT). OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a novel high-dose hydroxychloroquine regimen in patients with PCT. METHODS: Sixty-five first episodes and 28 recurrent episodes of PCT were treated with hydroxychloroquine, 250 mg three times daily, for 3 days. In patients with a high urine porphyrin concentration a single phlebotomy of 500 ml was performed before therapy of the first episode. Modified high-dose hydroxychloroquine regimens were used in patients with markedly elevated liver transaminases with or without associated chronic liver disease. RESULTS: Long-term follow-up data showed an overall relapse rate of 33%, significantly higher among male patients (45%) than among female patients (17%) (p less than 0.05). A transient hepatotoxic reaction occurred in the majority of patients. The reaction seemed to be especially severe among phlebotomized female patients. CONCLUSION: Hydroxychloroquine, 250 mg three times daily, is a rapid, efficacious, and safe treatment in patients with PCT. PMID- 1597549 TI - Metastatic cutaneous lesions in children and adolescents with a case report of metastatic neuroblastoma. AB - A child with neuroblastoma metastatic to the skin is reported. A review of the literature revealed that neuroblastoma and leukemia are the neoplasms most frequently associated with cutaneous metastases in children and adolescents. The low incidence of these lesions and their high malignant potential are two important factors that emphasize the pivotal role the dermatologist plays in prompt diagnosis and early referral. PMID- 1597551 TI - Is systemic nickel important? PMID- 1597550 TI - Guidelines of care for nevi I (nevocellular nevi and seborrheic keratoses). Committee on Guidelines of Care. Task Force on Nevocellular Nevi. PMID- 1597552 TI - What is segmental neurofibromatosis? PMID- 1597553 TI - Sqwish Ball dermatitis. PMID- 1597554 TI - Periumbilical perforating pseudoxanthoma elasticum. PMID- 1597555 TI - Nickel dermatitis recall during disulfiram therapy for alcohol abuse. PMID- 1597556 TI - The effect on liver transaminases of phototoxic drugs used in systemic photochemotherapy. PMID- 1597557 TI - Pseudoxanthoma elasticum-like papillary dermal elastolysis. PMID- 1597559 TI - Oral and labial melanotic macules in a patient infected with human immunodeficiency virus. PMID- 1597558 TI - Dyshidrosiform pemphigoid: report of three cases. PMID- 1597560 TI - Bile pigment deposition at sweat pores of patients with liver disease. PMID- 1597561 TI - Umbilical metastasis from urinary bladder carcinoma. PMID- 1597562 TI - HLA typing in actinic prurigo. PMID- 1597563 TI - HLA typing in polymorphic light eruption. PMID- 1597564 TI - Unmasking myelin proteins in neurothekeoma. PMID- 1597565 TI - Tricholemmal carcinoma: clinicopathologic study of 10 cases. AB - Tricholemmal carcinoma (TLC) is a cutaneous adnexal tumor with presumed external hair sheath differentiation. In order to better understand the salient features of this neoplasm, we analyzed the histologic and clinical findings in 10 cases of TLC. Eight patients were males, and two were female; they ranged in age from 55 88 years. Each tumor occurred in hair bearing, sun-exposed skin, and involved the scalp, face, trunk, or upper extremities. The lesions were usually slightly raised, pale tan or reddish, and keratotic; were usually present for less than 1 year; and measured 0.4-2.0 cm. All of them were treated by wide local excision; neither recurrence nor metastasis was reported after 11 to 92 months of clinical followup. Histologically, each TLC was composed of a lobular proliferation centered on the pilar apparatus. Cells with glycogen-rich, mucin-negative, clear or pale eosinophilic cytoplasm predominated. Brisk mitotic activity (4-39 mitoses per 10 high power fields) was typical. Involvement of the interfollicular epidermis was invariably noted, with superficial ulceration in seven tumors. Transitional zones between TLC and the adjacent epidermis were not seen, although pagetoid spread occurred in two examples. Invasion of reticular dermis was present in eight cases, with infiltration to mid-dermis in five TLC. All tumors exhibited areas of tricholemmal type keratinization; dyskeratotic cells were noted in six examples. Hyperkeratosis and parakeratosis were variably present as well. Actinic damage was a constant feature. Despite local invasion at diagnosis, the clinical course of TLC was indolent in all cases. PMID- 1597566 TI - Prognostic significance of proliferation and motility in primary malignant melanoma of the skin. AB - The metastatic cascade depends on the presence of tumor cells which are capable of proliferation as well as of invasion with active motility. In the present study, it was examined whether the demonstration of both features in the primary lesion of malignant melanoma of the skin carries prognostic significance. Proliferation was assessed by mitotic counts and Ki 67 staining, and motility was estimated by image analysis and comparison of the image analysis results with computer simulations; 27 cases of primary malignant melanoma with a maximum vertical tumor thickness exceeding 1 mm were prospectively sampled. Mitotic counts were carried out on H & E stained sections, image analysis of the tumor pattern on S-100 immunostained paraffin slides, and Ki 67 labeling of actively cycling cells was evaluated on frozen sections. Neither proliferation nor pattern analysis alone provided a significant prognostic result with respect to overall survival and to metastasis free survival. The estimates of motility, derived from a combination of pattern analysis and proliferation values, however, proved to be significant predictors of overall survival and metastasis-free survival (log rank test: p less than or equal to 0.05). The motility features were superior to Clark level and Breslow index in this set of cases. The results demonstrate that the assessment of tumor cell proliferation and motility in histological sections may reflect the metastatic potential of primary malignant melanomas of the skin. PMID- 1597568 TI - Scabietic nodules: a dermatopathologic and immunofluorescent study. AB - Mites and their eggs were thought to be rarely found in nodular lesions of scabies. However, serial sections from 27 scabietic scrotal papules or nodules revealed mite parts in 22% (6/27). This supports the contention that scabietic nodules may result from persisting antigens of mite parts. In contrast to previous studies, vasculitis with fibrinoid degeneration was uncommon (3/27) in our series. This discrepancy may be due to the timing of the biopsies: 2 of 3 cases with vasculitis were associated with diffuse dense infiltration, and vasculitis may be a late event in the development of scabietic nodules. The specificity of immunoreactant deposits along the epidermodermal junction (EDJ) in scabies is controversial. In our study, direct immunofluorescence (DIF) was performed on 13 scabietic nodules. Four (31%) showed immunoreactants at the EDJ and two on blood vessels. Because of the relatively low positive rate, the low intensity of fluorescence, and 3 of 4 cases with positive immunoreactants having only a single class of immunoglobulin, the deposition may only be secondary to inflammation instead of a specific type II immunologic reaction to scabies. PMID- 1597567 TI - Epidermolysis bullosa complicated by squamous cell carcinoma: report of 10 cases. AB - Epidermolysis bullosa (EB) refers to a group of hereditary mechano-bullous conditions, many of which are associated with chronic scarring. Several forms of the disease have been reported in association with cutaneous malignancy. We present a series of 10 EB patients (eight generalised recessive dystrophic EB, one dominant dystrophic EB, one non-lethal junctional EB) aged 24-55 years with a total of 29 squamous cell carcinomas (SCC). Three patients died from metastatic disease associated with invasive, poorly differentiated SCC. Six cases had multiple primary SCC, including three patients with simultaneous multifocal disease. Twenty-eight of the 29 SCC arose on the limbs. Histology revealed that most of the SCC were well or moderately differentiated (22/29). Unusual histological findings included two verrucous SCC, as well as a spindle cell (angiosarcoma-like) SCC. Most of the SCC developed in areas of chronic non healing ulceration (10/29) or longstanding hyperkeratotic crusting (14/29). The dermis around or beneath the carcinomas was densely scarred, more so than in non malignant areas. In some cases it was difficult to distinguish the clinical appearances of certain areas of chronic ulceration, scarring, and crusting typical of dystrophic EB from many of the SCC. This study underlines the need for constant vigilance for the development of carcinomas in this group of patients, the occasional diagnostic difficulty, and the potential for metastasis. PMID- 1597569 TI - Primary osteosarcoma of the skin. AB - Primary cutaneous osteosarcoma is extremely rare. An extraskeletal osteosarcoma of the skin occurring in the popliteal region of a 51-year-old woman is described. There were no associated predisposing conditions. PMID- 1597570 TI - Verruciform xanthoma in association with discoid lupus erythematosus. AB - Verruciform xanthoma (VX) is an uncommon lesion occurring primarily in the oral cavity. Cutaneous lesions are much less common and they preferentially arise on anogenital skin. They are not necessarily associated with a pre-existing inflammatory process. We report a VX in association with a long-standing lesion of discoid lupus erythematosus (DLE) on the scalp of a 34-year-old black woman. This association, which to our knowledge has not been previously reported, is consistent with the proposed pathogenetic mechanism of entrapment and subsequent degeneration of epithelial cells in the papillary dermis of VX. Histological distinction of VX from squamous cell carcinoma, with which this lesion may be clinically confused, is straightforward. PMID- 1597571 TI - Dermatomyofibroma: a case of fibromatosis revisited. PMID- 1597572 TI - Tricholemmal carcinoma. PMID- 1597573 TI - Dermatomyofibroma. A benign cutaneous, plaque-like proliferation of fibroblasts and myofibroblasts in young adults. AB - We report nine examples of a distinct cutaneous plaque-like proliferation of fibroblasts and myofibroblasts. Eight of nine lesions were located in or around the shoulder, including axilla and upper arm. There was a predominance of women to men of 8:1. The lesions measured from 1 to 2 cm in greatest diameter. All patients were young adults (mean age 29.8 yr). All lesions involved the reticular dermis in a plaque-like fashion and extended to the upper part of the subcutaneous septa in seven cases. The lesions consisted of a proliferation of very uniform slender spindle-shaped cells arranged as well-defined elongated and intersecting fascicles with a predominantly parallel arrangement to the skin surface. There was no evidence of cytologic atypia and mitotic figures were infrequent. The spindle-shaped cells were separated by thin collagen fibers. Elastic fibers were preserved and some of them appeared thicker than normal. All adnexal structures were spared. Immunohistochemistry revealed that the cells stained positively for vimentin and muscle actin, but lacked smooth-muscle specific actin, desmin, and S-100 protein. Some dermal dendrocytes stained positively for Factor XIIIa, but the spindle-shaped cells were negative. Electron microscopy studies revealed a mixture of fibroblasts, myofibroblasts, and undifferentiated mesenchymal cells. All lesions were treated by conservative excision; follow-up information revealed no evidence of recurrence. We name this distinct lesion dermatomyofibroma. To the best of our knowledge, this entity has not been previously described in the literature. PMID- 1597574 TI - Application of PhastSystem to the resolution of bovine milk proteins on urea polyacrylamide gel electrophoresis. AB - Optimal conditions were established for alkaline urea-PAGE using modified precast, ultrathin gradient gels on the automated PhastSystem. Profiles of milk proteins showed that the caseins and whey proteins resolved extremely well. Major bands were observed for alpha s1-casein and beta-casein, and alpha s2-casein appeared as a well-resolved doublet. In contrast, kappa-casein separated from other caseins as a faint doublet, and purified kappa-casein appeared as one major and one minor band. Whey proteins (serum albumin, alpha-lactalbumin, beta lactoglobulin) separated into broad bands resolved from each other and from the caseins. Partially (40%) dephosphorylated whole casein showed multiple bands for alpha s1-casein and beta-casein at different levels of phosphorylation. Separation of genetic phenotypes was observed for beta-lactoglobulin A and B; alpha s1-casein A, B, and C; and beta-casein A, B, and C. Electrophoretic patterns of milk proteins extracted from cheese samples varied among the different types of cheeses. Our modified procedure provides researchers with a rapid technique to separate both caseins and whey proteins on the same urea gel according to their charge to mass ratios. PMID- 1597575 TI - Benzaldehyde, citral, and d-limonene flavor perception in the presence of casein and whey proteins. AB - The effect of sodium caseinate and whey protein concentrate on benzaldehyde, d limonene, and citral flavor intensity was determined by quantitative descriptive analysis deviation from reference using a 12-member trained panel. The concentrations for the benzaldehyde, d-limonene, and citral flavor intensity references were 17.8, 53.0, and 19.8 ppm, respectively. The concentration for both protein references was .25%. Flavored protein solutions were held for 17 h at 6 degrees C and contained benzaldehyde (17.8 ppm), d-limonene (53 ppm), or citral (19.8 ppm) and 2.5% sucrose with 0, .125, .25, or .5% protein. Benzaldehyde flavor intensity declined as the whey protein concentrate concentration increased from 0 to .5%. There was no significant difference in benzaldehyde flavor intensity with casein compared with the reference. The d limonene flavor intensity declined as the protein concentration increased. Panelists found no significant drop in citral flavor intensity with casein or whey protein. Decreased benzaldehyde and d-limonene flavor intensity in the presence of whey protein concentrate or casein may be due to nonpolar interactions (casein), interaction with nonpolar binding sites, cysteine-aldehyde condensation, or Schiff base formation (whey protein concentrate). PMID- 1597576 TI - Stimulation of milk yield and feed intake by bovine placental lactogen in the dairy cow. AB - A 6 x 6 Latin square design was used to test the effects of recombinant bovine placental lactogen on milk yield, milk composition, feed intake, and blood hormone and metabolite levels in nonpregnant lactating cows. The six treatments (5, 10, 20, and 40 mg/d of placental lactogen, water as negative control, and 20 mg/d of bST as positive control) were administered by subcutaneous injection twice daily for 9 d. Blood samples were taken during the last 5 d of the treatment period. The three highest doses of placental lactogen increased milk yield, and there was a linear dose effect, although placental lactogen was less potent than bST. Milk concentrations of lactose, protein, and fat were not altered by any of the treatments. Dry matter intake was increased by two of the doses of placental lactogen, but not by bST. Blood urea N concentration was decreased in a dose-dependent manner by placental lactogen and was also decreased by bST. Similarly, serum insulin-like growth factor-I was increased in a dose dependent manner by placental lactogen and was also increased by bST. Plasma concentrations of NEFA and glucose were increased by bST, but placental lactogen had little or no effect on either of these parameters. Thus, placental lactogen appears to act, in part, as a weak somatotropin agonist; however, it also appears to have specific activities, e.g., stimulating feed intake. PMID- 1597577 TI - Evaluation of a gel teat cleaning and sanitizing compound for premilking hygiene. AB - A gel was developed and tested for cleaning and sanitizing cows teats for milking. Thirty lactating Holstein cows were divided into three groups of 10 each and assigned to three premilking hygiene treatments for 10 wk as follows: 1) cleaning teats with gel, allowing 30 s of contact time, and wiping residual gel off with paper towel; 2) washing teats with water and drying them with paper towel; 3) washing teats with water, drying with paper towel, predipping with .5% iodophor solution, allowing 30 s of contact time, and drying with paper towel. Individual cow composite milk and teat end swab samples were collected. The gel and predip treatments resulted in less bacterial contamination of milk and teat ends. The gel treatment had an advantage over wash and predip treatments in lower SCC and reduced mastitis. Parlor throughput was greatest for gel and wash treatments. The wash treatment group had highest SCC, bacteria in milk and on teat ends, and mastitis. Milk iodine content was low and similar for the three treatments. Daily milk production and fat and protein percentages were not affected by treatments. The gel treatment was effective, efficient, and provided good hygiene. PMID- 1597579 TI - Managerial determinants of intramammary coliform and environmental streptococci infections in Ohio dairy herds. AB - Forty-eight dairy herds in Ohio were selected as a stratified random sample for participation in a disease monitoring study to relate the prevalence of IMI with coliform and environmental streptococci to herd management and environmental conditions. Management and environmental conditions were assessed by farm inspection and by an interview with the dairy producers. A separate analysis for each independent variable identified many potential disease determinants. A multivariable analysis of a covariance model to predict the prevalence of coliforms had 6 model df (R2 = .47). Increased prevalence of coliform infection was associated with an increased amount of milk remaining in the udder after milking, use of free stalls, regular use of a running water wash, increased person hours per cow spent milking, and poor sanitation. The multivariable model for environmental streptococci used 5 model df (R2 = .51). Increased prevalence of environmental streptococci was associated with poor sanitation, increased number of days dry, use of tie stalls, no use of a shared wash cloth, and no use of an individual dry cloth. PMID- 1597578 TI - In vitro germicidal activity of teat dips against Nocardia asteroides and other udder pathogens. AB - Nine commercial teat dip formulations containing 1.94% linear dodecylbenzene sulfonic acid, or 1% available iodine from nonylphenoxypoly (ethyleneoxy) ethanol iodine complex, or .5% chlorhexidine acetate were tested for contamination with aerobic and anaerobic bacteria and their in vitro germicidal activity against Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli, and Nocardia asteroides. All products were free of bacteria when neutralized samples were tested on blood agar or liquid thioglycollate media. To test for in vitro efficacy, each teat dip preparation was mixed with a suspension of one of the pathogenic test organisms containing 10(8) bacteria/ml (final concentration) for .5 to 15 min. Viable bacteria were evaluated by direct plating of neutralized aliquots and by filtration techniques. All products were effective against E. coli, Staph. aureus, and Strep. agalactiae. With N. asteroides, the direct plating method gave equivocal results. The filtration experiments indicated that all teat dips containing dodecylbenzene sulfonic acid and nonylphenoxypoly (ethyleneoxy) ethanol-iodine complex were effective against all four pathogens. Three of the teat dips containing chlorhexidine acetate were ineffective against N. asteroides. The fourth teat dip, containing chlorhexidine acetate and an emollient, was partially effective. PMID- 1597580 TI - 1 alpha-hydroxycholecalciferol for the treatment of the downer cow syndrome. AB - Seventeen Holstein cows that showed clinical and biochemical symptoms (hypocalcemia and hypophosphatemia) of parturient hypocalcemia within 48 h postcalving and did not respond to Ca therapy were divided into two groups. Eight cows received a second intravenous Ca infusion 24 h after the first one. This treatment increased plasma Ca concentration but had no significant effect on phosphatemia, and the cows remained unable to rise and stand during 48 h following this second Ca infusion. The 9 other cows received 1 alpha hydroxycholecalciferol (1 microgram/kg of BW, half the dose intravenously, the other half intramuscularly). 1 alpha-Hydroxycholecalciferol induced a significant increase in plasma P concentration and recovery of all the 9 cows within 12 h after this treatment. PMID- 1597581 TI - Synthesis of lactoferrin and transport of transferrin in the lactating mammary gland of sheep. AB - Two iron-binding proteins, lactoferrin and transferrin, are present in ruminant milk. Lactoferrin commonly has been assumed to be a product of mammary synthesis, but the origin of milk transferrin has not been elucidated. The objective of this experiment was to study the synthesis and distribution of these two proteins in the mammary gland of sheep. Explants from lactating mammary gland of sheep have been cultured in the presence of [3H]leucine to determine rates of synthesis of lactoferrin and transferrin. After incubation, [3H]lactoferrin was found, but labeled transferrin was not. The capacity of the mammary gland to synthesize lactoferrin decreased markedly in the first 24 h of lactation. Immunohistochemical techniques were utilized to identify the locations of lactoferrin and transferrin in the mammary gland. Transferrin was found in the colostrum contained in the alveolar lumen, in the cytoplasm of the secretory cells, and in the connective tissue between the mammary acini. High concentration of transferrin was found in the basal membrane of the secretory alveolar cells, mainly in those near capillary vessels. Lactoferrin was found in the colostrum and in the cytoplasm of secretory cells with a more homogeneous distribution than transferrin. The connective tissue stained negative for lactoferrin. These results suggest that, although lactoferrin is synthesized by mammary gland of the sheep, transferrin comes from blood serum, probably by a receptor-mediated mechanism of transcytosis. PMID- 1597582 TI - Evaluation of various measures of and factors influencing feed efficiency of dairy cattle. AB - Early part records for milk yield and feed consumption of 2230 first lactation purebred and crossbred dairy cows were analyzed to evaluate various measures of feed efficiency. Corrected milk yield was estimated by adjusting the second 8 wk of milk yield for differences in weight of TDN consumed during wk 9 to 16, percentage of TDN derived from concentrate, and BW.75. Corrected milk yield is an estimate assuming that cows are the same size and consume the same amount of feed. Hence, it represents an expression of feed efficiency. Net feed efficiency, gross efficiency, corrected milk yield, and wk 9 to 16 milk were analyzed simultaneously. Coefficient of determination for net efficiency (.51) and gross efficiency (.72) were lower than that of milk (.82), whereas corrected milk yield had a coefficient of determination similar to that of milk. Hence, the use of ratios to define feed efficiency was less accurate than using corrected milk yield. Effects of genetic groups, stations, season of freshening, year of freshening, and heterosis were similar for gross efficiency and corrected milk yield, but different from those for milk. Therefore, corrected milk yield performed the same function as feed efficiency with higher accuracy. PMID- 1597583 TI - Influence of cation-anion balance on feed intake, body weight gain, and humoral response of dairy calves. AB - The objective of this study was to examine the influence of diets with varying cation-anion balance on performance and humoral responses in young, growing dairy calves. Twenty-eight Holstein and 4 Jersey female calves were blocked at 56 to 70 d after birth according to breed and age and assigned randomly to dietary treatments of 0, 21, 37, and 52 meq(Na + K) - Cl/100 g of dietary DM. Diets were based on cracked corn, dried brewers grains, and oats and were fed for 8 wk. Feed intake and average daily gain tended to increase quadratically, being highest for calves fed the +37-meq diet and lowest for those fed the 0-meq diet. Blood and urine pH increased linearly with increasing dietary cation-anion balance. Plasma Ca increased linearly, and Mg and Cl decreased linearly with increasing cation anion balance. Plasma Na and P were unaffected by dietary treatments. Urinary Ca, Mg, and Cl excretions decreased linearly; urinary P, Na, and K excretion increased linearly with increasing dietary cation-anion balance. Blood pH increased linearly with increasing dietary cation-anion balance. Blood partial pressure of CO2 and HCO3 increased concurrently with increasing dietary cation anion balance. Results indicate that altering cation-anion balance may impact DMI and average daily gain in the young ruminant. PMID- 1597584 TI - Nitrogen metabolism in rumen and whole digestive tract of lactating dairy cows fed grass silage. AB - Effects of wilting of grass prior to ensiling on OM intake, ruminal digestibility, efficiency of bacterial protein synthesis, and amount and composition of duodenal N fraction were examined using four lactating Holstein cows. Direct-cut or wilted grass silages were fed for ad libitum intake and supplemented with 5.0 or 5.3 kg of concentrate, respectively. Milk yield was 18.1 and 21.2 kg/d with direct-cut versus wilted silage, and milk protein and fat contents were 2.63 and 4.60% with direct-cut versus 2.75 and 4.27% with wilted silage, respectively. Wilting of the grass (from 17 to 38% DM) increased OM intake but had no effect on ruminal digestibility. Total N flow and amounts of different AA in proximal duodenum were increased, and the difference was principally of bacterial origin. The efficiency of bacterial protein synthesis in rumen was related to dilution rate of liquid phase and to the time devoted to ruminating. These results indicate that the passage of bacterial protein to the lower digestive tract is a key factor for improving the assimilation of the soluble N fraction of grass silage and that this phenomenon is related to chewing activity. PMID- 1597585 TI - Ventilation system to minimize airborne bacteria, dust, humidity, and ammonia in calf nurseries. AB - We installed a ventilation system that minimizes airborne bacteria, dust, humidity, and ammonia levels; conserves animal heat during the winter months by precise control of the amount of fresh air admitted to the calf nursery; and prevents cross transfer of airborne pathogens between neighboring calves by providing uniform air distribution throughout the calf nursery. Because of the effectiveness of air filtration and uniform air distribution within the nurseries, respiratory problems of calves were reduced greatly. Airborne dust and bacteria as small as .5 mu were filtered from the air. PMID- 1597586 TI - Changes in lipid composition of calf tissues by excess dietary zinc. AB - In a previous study, very high Zn (1000 ppm) prevented most of the tissue lipid increases caused by very high Cu (1000 ppm), and this investigation was conducted to study whether Zn had a direct effect on lipid metabolism or simply acted indirectly by inhibiting excess Cu activity. Calves were fed basal dietary Cu (10 ppm), and lipid composition of heart, liver, and blood plasma was measured as affected by control (40 ppm in DM), high (500 ppm), or very high (1000 pm) Zn intakes. Supplementation with 1000 ppm of Zn did not cause any marked quantitative changes in tissue lipids (e.g., lipid classes, oleic, or stearic acids), suggesting that, in the previous study, Zn had mainly interfered with excess Cu effects on lipids rather than with lipid metabolism directly. However, there were two exceptions. Adding 1000 ppm of Zn to basal Cu ration 1) reduced concentration and changed the fatty acid composition of plasma cholesterol esters, both of which are indicative of excess Zn inhibiting lecithin:cholesterol acyltransferase activity, and 2) altered the desaturation and elongation of the essential fatty acids and their concentration in tissue phospholipids. This latter effect of excess Zn conceivably could be important in changing the structure and function of cell membranes and in the production and activity of prostanoids and leukotrienes. PMID- 1597587 TI - Power of likelihood ratio tests for heterogeneity of intraclass correlation and variance in balanced half-sib designs. AB - Statistical power of likelihood ratio tests was investigated for detection of heterogeneous variances and intraclass correlation in balanced half-sib designs. Powers of likelihood ratio tests were obtained from simulations. For half-sib designs of sires nested within herds, true intraclass correlations and phenotypic variances, and estimates thereof, were repeatedly sampled, and likelihood ratio tests were conducted. The power for detecting heterogeneity of intraclass correlations was low, but the power for detecting heterogeneous phenotypic variances was nearly always 100%. For balanced cross-classified designs, sires had progeny in all herds, and data were simulated by assuming that heterogeneity of between- and within-sire components was the result of a herd-dependent scale effect. Using this model, the power to detect heterogeneous between-sire components was substantially higher than the corresponding power to detect heterogeneous intraclass correlations in the nested design. It seems unlikely that reliable inference about heterogeneity of genetic variances or heritabilities between individual herds from daily cattle field data can be made. PMID- 1597588 TI - The importance of maternal lineage on milk yield traits of dairy cattle. AB - Maternal lineage effects on milk yield traits, considered indicative of cytoplasmic inheritance, were evaluated with animal models. Cattle were from a selection experiment begun in 1968. Maternal pedigrees were traced to the first female member in the Holstein-Friesian Herdbook; purchased cows entering the herd, considered foundation females, were assigned to maternal lineage groups. All models accounted for year-season of calving, parity, and selection lines. Maternal lineage effects were included in a repeated records model with cow effects and preadjustment for sire and maternal grandsire transmitting abilities. Maternal lineage accounted for 5.2, 4.1, and 10.5% of phenotypic variation of preadjusted records of milk yield, fat yield, and fat percentage, respectively. Maternal lineage was evaluated as a fixed effect in an animal model including random animal and permanent environmental effects. Maternal lineage significantly affected fat percentage but not milk yield. Maternal genetic (nuclear) effects and their covariance with additive animal effects did not significantly account for additional variation nor did they influence maternal lineage estimates. Maternal lineage affected calculated net energy of milk but was not important for SNF yield or concentration. Maternal lineage influenced fat percentage, energy concentration, and, to a lesser extent, fat yield in milk of dairy cattle. PMID- 1597589 TI - Genetic parameters for yield traits of Holsteins, including lactose and somatic cell score. AB - First lactation milk, fat, protein, and lactose yields and percentage yields were analyzed using a multiple-trait sire model including herd-year-season, sire group, and age of cow as fixed effects. Somatic cell score was fit both as a fixed effect in the model and as an additional dependent variable in two analyses with almost identical results. Variance components were estimated using REML with an expectation-maximization algorithm including sire relationships. Lactose means ranged from 4.84 to 4.97% across three dairy breeds. Data used to estimate variance components were first lactation Holstein records collected from 1986 to 1988 from 5246 daughters of 392 AI sires. Heritability estimates were .30, .29, .27, and .26 for milk, fat, protein, and lactose yields; .45, .47, and .53 for fat, protein, and lactose percentage yields; and .16 for somatic cell score. Genetic correlations of lactose percentage with milk, fat, protein, fat and protein percentages, and somatic cell score were -.30, -.16, -.21, .10, .29, and .11, respectively, and phenotypic correlations were -.08, -.02, .01, .11, .29, and -.15. PMID- 1597590 TI - Genetic value of herd life adjusted for milk production. AB - Cow herd life adjusted for lactational milk production was investigated as a genetic trait in the breeding objective. Under a simple model, the relative economic weight of milk to adjusted herd life on a per genetic standard deviation basis was equal to CVY/dCVL where CVY and CVL are the genetic coefficients of variation of milk production and adjusted herd life, respectively, and d is the depreciation per year per cow divided by the total fixed costs per year per cow. The relative economic value of milk to adjusted herd life at the prices and parameters for North America was about 3.2. An increase of 100-kg milk was equivalent to 2.2 mo of adjusted herd life. Three to 7% lower economic gain is expected when only improved milk production is sought compared with a breeding objective that included both production and adjusted herd life for relative value changed +/- 20%. A favorable economic gain to cost ratio probably exists for herd life used as a genetic trait to supplement milk in the breeding objective. Cow survival records are inexpensive, and herd life evaluations from such records may not extend the generation interval when such an evaluation is used in bull sire selection. PMID- 1597591 TI - Incidence of atresia coli and relationships among the affected calves born in one herd of Holstein cattle. AB - Eighteen cases of atresia coli were observed in the University of Illinois Holstein herd from 1974 through August 1983 in 2367 births. The overall incidence of the abnormality was .76% during this period. All of the affected calves were related to one another, and 15 of them were inbred. More calves were born with atresia coli from dams in which pregnancy was diagnosed prior to d 41 of gestation than from dams in which pregnancy was diagnosed later. Early pregnancy diagnosis in dams may contribute, but was not essential, to atresia coli in Holstein calves. Thirteen of the affected calves were males. The proportion of calves aborted or born dead among the affected calves was greater than expected from the incidence of aborted or born dead among contemporary calves. PMID- 1597592 TI - Sound scattering by a cylindrical shell reinforced by lengthwise ribs and walls. AB - An analytical solution is derived for the acoustic response of submerged thin walled ring cylindrical shell containing lengthwise stiffening members: internal stringers and walls. On the basis of the analysis of the acoustic pressure versus time diagrams the stiffener-borne wave-generation mechanisms are traced. Shown is that the shell/stiffener junctions act as additional entry and exit points of circumferential waves circulating in the shell and the fluid. The stiffening members cause transformations of circumferential waves from one propagation type to another. PMID- 1597593 TI - Analysis of acoustic scattering in fluids and solids by the method of fundamental solutions. AB - The method of fundamental solutions (MFS) is a boundary method for the numerical solution of certain elliptic boundary value problems. In the MFS, the approximate solution is a linear combination of fundamental solutions of the governing partial differential equation, with singularities placed outside the domain of the problem. In the present paper, the MFS is applied to acoustic scattering in fluids. The singularities are allowed to move during the solution process from arbitrary locations to more optimal locations. Numerical results demonstrate that the "fictitious eigenfrequency" difficulty encountered with the boundary element method (BEM) is not present in the MFS. In addition, MFS results obtained by the use of fixed singularities are presented for scattering of waves in elastic solids. PMID- 1597594 TI - Equivalent boundary conditions for thin orthotropic layer between two solids: reflection, refraction, and interface waves. AB - Boundary conditions for an interface between two solids are introduced to model a thin orthotropic interface layer. The plane of symmetry of the layer material coincides with the incidence plane. Boundary conditions relating stresses and displacements on both sides of the interface are obtained from an asymptotic representation of the three-dimensional solutions for an interface layer whose thickness is small compared to the wavelength. The results for anisotropic boundary conditions are a generalization of our previous results [S. I. Rokhlin and Y. J. Wang, J. Acoust. Soc. Am. 89, 505-515 (1991)] for an isotropic viscoelastic layer. The interface boundary conditions obtained contain interface stiffness and inertia and terms involving coupling between normal and tangential stresses and displacements. The applicability of such boundary conditions is analyzed by comparison with exact solutions for reflection. As in the isotropic case, fundamental boundary-layer conditions are introduced containing only one transverse or normal mass or stiffness. It is shown that the solution for more accurate interface boundary conditions, which include two inertia elements and two stiffness elements, can be decomposed into a sum of fundamental solutions. Interface waves along such an interface are considered. Characteristic equations for these waves are obtained in closed form for different types of approximate boundary conditions and the velocities calculated from them are compared to the exact solution. It is shown that retention of the terms describing coupling between normal and transverse stresses and displacements is essential for calculating the velocity of an antisymmetric interface wave. PMID- 1597595 TI - Ambient noise measurements from 100 Hz to 80 kHz in an Alaskan fjord. AB - Measurements covering a broad frequency range from 100 Hz to 80 kHz have been made in Behm Canal, Alaska. This site represents a fairly deep embayment (400 m) with a soft bottom (porosity of about 0.8) and, hence, the noise detected at the hydrophones is affected negligibly by multipath contributions except possibly at the lowest frequencies. Data were gathered over a wide range of wind speeds (0 to 15 m/s) and during periods of rain and snow. Several unique and noteworthy results were obtained. Foremost was the observation that the wind-generated noise level measured during the winter was approximately 5 dB lower than during the summer for the same wind speeds and air-sea temperature differences (air temperature about the same as or colder than the sea surface). The summer data agree well with the most recent published measurements and are approximately 2 dB higher than the standard Knudsen/Wenz reference spectra. It appeared that below freezing air temperatures and snow were responsible for the 5 dB offset between the summer and winter data. Most reported wind noise measurements are restricted to frequencies less than 20 kHz. Those that go beyond this frequency display a noticeable hump above the usual--17 dB/decade power-law slope, and the Behm Canal measurements show that this hump continues to 80 kHz where the spectrum rejoins the extension of the canonical power-law slope. PMID- 1597596 TI - The effects of viscoelasticity on the reflection and transmission of ultrasonic waves by an orthotropic plate. AB - In this paper both theoretical and experimental investigations on the reflection and transmission of an incident plane wave by immersed viscoelastic orthotropic plates are presented. Taking the anisotropy of the layer into account the reflection and transmission coefficients are expressed in terms of nine complex elastic constants. In agreement with the Snell's laws, any waves generated in the layer are bulk heterogeneous plane waves. Using a method already described in the isotropic case, the reflection and transmission coefficients are obtained as a function of the reflection and refraction coefficients of bulk heterogeneous plane waves at the two single solid/liquid interfaces, which limit the plate. In this way, these coefficients can be easily expanded in Debye's series. In addition, for many incident and azimuthal angles, the calculations are compared with trial results on a composite made of unidirectional carbon fibers and epoxy matrix. Finally, by the measurement of the variation of attenuation versus the frequency, a linear model permits the computations in a large frequency range. Conclusions are carried out regarding the use of the LLW method in the inverse problem to recover elastic constants of composite materials. PMID- 1597597 TI - Multiple reflected beam synthesis of fields excited by a high-frequency oblique beam input in an elastic plate. AB - Transducer-excited beams provide important diagnostic tools for ultrasonic nondestructive evaluation (NDE) of elastic materials. For bonded multilayer elastic plates, an obliquely injected high-frequency compressional (P) beam creates interior dynamic fields that are sensitive to weak debonding between the layers. In an effort to clarify the wave phenomena that are operative under these conditions of excitation, a highly idealized model has been chosen wherein a lossless plate in vacuum is insonified by an internal oblique P-beam source. This problem was analyzed in a previous investigation [Lu, Felsen, and Klosner, J. Acoust. Soc. Am. 87, 42-53 (1990)] by expressing the total field in terms of a sum of P-S (vertically polarized or in-plane) coupled normal modes. While the resulting field assumed oscillatory modal patterns at interior cross sections far from the source region, the modally synthesized field near the source clearly outlined profiles interpretable as incident and singly or multiply reflected P-S coupled beams. The problem is therefore studied here directly by Gaussian beam tracing as implemented via our previously employed complex ray field algorithm. The results clarify the observed phenomena by revealing the successive buildup from initially well-resolved beams into oscillatory mode patterns synthesized by overlapping multiples. For the same idealized model, the beam algorithm has been applied elsewhere to the detection and identification of weak debonding in a layered plate [Felsen and Zeroug, J. Acoust. Soc. Am. 90, 1527-1538 (1991)]. With an understanding of the physical mechanisms that arise in the beam-to-mode conversion, one may now explore how their utility is affected under realistic NDE conditions. PMID- 1597598 TI - Effects of higher-order harmonics on phase determination in an ultrasonic interferometer. AB - The effect of higher-order harmonic components on phase determination were analyzed to improve the accuracy of transient time measurement in an ultrasonic interferometer with a quadrature detector system. Under ideal conditions the locus of output signals of the phase sensitive detector forms a circle on the phase plane as the frequency changes and any nonideal factor would distort the circle, leading to erratic phase determination. This analysis has shown that the nth-order contribution to the phase is mostly determined by the product of the amplitudes of corresponding components of the reference and echo signals fed to the phase detector. The distortion parameters were obtained by least-squares fitting of the data to the distorted circle in the phase plane, and compared with those roughly estimated from the frequency components of the reference and echo signals. The exemplary numerical phase corrections for the third-order harmonics were carried out, so as to illustrate the improvement in the accuracy of the ultrasonic interferometer. PMID- 1597599 TI - Object classification and acoustic imaging with active sonar. AB - The theoretical underpinnings of underwater acoustic classification and imaging using high-frequency active sonar are studied. All essential components of practical classification systems are incorporated in a Bayesian theoretic framework. The optimum decision rules and array processing are presented and evaluated. A systematic performance evaluation methodology is derived. New results quantify the relationship between classifier performance and object geometry, acoustic imaging, and the accuracy of a priori knowledge infused into the processor. PMID- 1597600 TI - On the degree of rigidity of the manubrium in a finite-element model of the cat eardrum. AB - It has always been assumed that the manubrium is in effect perfectly rigid. In this paper, a more realistic model of the manubrium is incorporated into an existing finite-element model of the cat eardrum. The manubrial thickness is based on a three-dimensional reconstruction from serial histological sections. After a review of the literature, a value of 2 x 10(11) dyn cm-2 is adopted for the Young's modulus of the bone. The mode of vibration of the model is investigated for different manubrial-thickness values and it is found that a significant degree of manubrial bending occurs in the model for realistic values of manubrial thickness. As a result of the bending, the frequency response at the umbo at high frequencies displays much higher amplitudes and larger phase lags than when the manubrium is rigid. The bending will also affect the displacements transmitted to the ossicular load, and introduce significant errors into estimates of such displacements based on measurements of umbo displacement even at frequencies as low as a few kHz. Recent measurements of manubrium vibrations in the cat ear provide experimental evidence of bending. PMID- 1597601 TI - Effect of ear-canal air pressure on evoked otoacoustic emissions. AB - The effect of ear-canal air pressure on click-evoked otoacoustic emissions was measured for pressures ranging from 200 to -200 daPa and stimulus levels ranging from 60-90 dB PeSPL. Positive and negative ear-canal pressures (relative to ambient pressure) reduced the emission amplitude by 3-6 dB. A spectral analysis of the emissions revealed that the effect of ear-canal air pressure is that of a high-pass filter with a cutoff frequency of 2600 Hz and a slope of 4 dB/oct. The spectral changes are the expected effect of an increase in stiffness of the middle ear and were independent of pressure polarity and click level. Ear-canal air pressure substantially reduced the reproducibility of the emission waveform, in many cases rendering the emission indistinguishable from background noise. The implication of these findings for hearing screening applications is that a high false alarm rate may occur in normal-hearing patients with intratympanic air pressures that are significantly different from ambient pressure. PMID- 1597602 TI - Comparison of frequency selectivity and consonant recognition among hearing impaired and masked normal-hearing listeners. AB - Frequency selectivity and consonant recognition were determined for normal hearing and hearing-impaired listeners using techniques that facilitate comparisons of performance among listeners whose absolute thresholds vary in magnitude and configuration. First, for each of six subjects with cochlear hearing loss, masked thresholds in notched noise and narrow-band-noise maskers were obtained and compared to results for three normal-hearing listeners whose thresholds were precisely matched to the impaired listeners' by masking with spectrally shaped broadband noise. Second, for hearing-impaired listeners and their masked normal-hearing controls, measurements of consonant recognition were obtained at several speech-presentation levels selected on the basis of articulation-index predictions to assure equal speech-spectrum audibility across listeners. The results suggest that frequency selectivity is poorer for hearing impaired listeners than for masked normal-hearing listeners, even when thresholds among subjects are equated, but the deviation from normal frequency selectivity is smaller than estimated from comparisons with normal-hearing listeners in quiet. Critical ratios for hearing-impaired listeners are equivalent to normal. Although frequency selectivity is reduced, there is no consistent difference in consonant recognition between hearing-impaired subjects and masked normal-hearing subjects, when performance is assessed under conditions that assure equal speech spectrum audibility across subjects. PMID- 1597603 TI - Discrimination and identification of modulation rate using a noise carrier. AB - Modulation-rate perception was measured for three tasks: a fixed-standard, forced choice discrimination task with a 500-ms interstimulus interval; a random standard, forced-choice discrimination task with an 8-s interstimulus interval; and an identification task. Thresholds were obtained for modulation rates from 14 224 Hz using noise carriers bandpass filtered from 500-4000 Hz, 500-1600 Hz, 1700 2800 Hz, and 2900-4000 Hz. The four bands yielded similar results except for modulation rates greater than 100 Hz, where the 500- to 1600-Hz thresholds were higher. Fixed-standard discrimination thresholds were about 3 Hz for modulation rates up to 66 Hz. The increase of thresholds for modulation rates above 66 Hz could be due to temporal resolution limits with a time constant of about 2-3 ms. For modulation rates above 100 Hz, critical-band filtering may further decrease sensitivity for the 500- to 1600-Hz noise band. Resolution in the random-standard discrimination task was similar to that for the identification task. Thresholds were elevated relative to fixed-standard thresholds except at the extremes of the stimulus range. In the random-standard discrimination task, a pronounced criterion bias was present for stimuli near the extremes of the range. Durlach and Braida's model [N. I. Durlach and L. D. Braida, J. Acoust. Soc. Am. 46, 372 383 (1969)] describes the data well and provides quantitative measures for our data in good agreement with those for intensity perception. PMID- 1597604 TI - The effect of interaural delay of the masker on masking-level differences in young and old adults. AB - Diotic (SoNo) thresholds and dichotic (S pi N pi tau) thresholds were measured for young and old adults using a 500-Hz pure-tone signal and broadband burst masking noise at 37 dB SPL/Hz. In the dichotic condition both the signal and the masker were phase reversed and the masker was presented with an interaural delay of 0.25, 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 3, or 5 ms. Masking-level differences (MLDs) were determined by subtracting dichotic thresholds from diotic thresholds. The SoNo thresholds for the old subjects did not differ significantly from those for the young subjects; however, when MLDs were plotted as a function of delay, the pattern of results differed significantly between young and old subjects. This difference in pattern was completely accounted for in terms of a delay-line version of Durlach's equalization and cancellation (EC) model [N. I. Durlach, in Foundations of Modern Auditory Theory, edited by J. V. Tobias (Academic, New York, 1972); B. A. Schneider and P. M. Zurek, J. Acoust. Soc. Am. 86, 1756-1763 (1989)] by assuming that temporal jitter increases with internal delay in young subjects but that it does not vary with the amount of internal delay in old subjects. PMID- 1597605 TI - Speech pattern hearing aids for the profoundly hearing impaired: speech perception and auditory abilities. AB - A family of prototype speech pattern hearing aids for the profoundly hearing impaired has been compared to amplification. These aids are designed to extract acoustic speech patterns that convey essential phonetic contrasts, and to match this information to residual receptive abilities. In the first study, the presentation of voice fundamental frequency information from a wearable SiVo (sinusoidal voice) aid was compared to amplification in 11 profoundly deafened adults. Intonation reception was often better, and never worse, with fundamental frequency information. Four subjects scored more highly in audio-visual consonant identification with fundamental frequency information, five performed better with amplified speech, and two performed similarly under these two conditions. Five of the 11 subjects continued use of the SiVo aid after the tests were complete. A second study examined a laboratory prototype compound speech pattern aid, which encoded voice fundamental frequency, amplitude envelope, and the presence of voiceless excitation. In five profoundly deafened adults, performance was better in consonant identification when additional speech patterns were present than with fundamental frequency alone; the main advantage was derived from amplitude information. In both consonant identification and connected discourse tracking, performance with appropriately matched compound speech pattern signals was better than with amplified speech in three subjects, and similar to performance with amplified speech in the other two. In nine subjects, frequency discrimination, gap detection, and frequency selectivity were measured, and were compared to speech receptive abilities with both amplification and fundamental frequency presentation. The subjects who showed the greatest advantage from fundamental frequency presentation showed the greatest average hearing losses, and the least degree of frequency selectivity. Compound speech pattern aids appear to be more effective for some profoundly hearing-impaired listeners than conventional amplifying aids, and may be a valuable alternative to cochlear implants. PMID- 1597606 TI - Temporal modulation transfer functions in patients with cochlear implants. AB - Thresholds for the detection of amplitude modulation were measured in cochlear implant patients as a function of modulation frequency. Three types of threshold measures were taken: detection of amplitude modulation, detection of low frequency sinusoidal current waveforms, and detection of beats in two-tone complexes. The temporal modulation transfer function (TMTF), defined as the plot of modulation detection thresholds as a function of modulation frequency, show low-pass filter characteristics with similar cutoff frequencies for all three tasks. The similarity of these three measures suggests a common temporal mechanism. While modulation detection differs somewhat in normal-hearing and implanted listeners, both exhibit the same general characteristics. The TMTFs are low pass with a cutoff frequency near 70 Hz for normal-hearing listeners and near 140 Hz for implanted listeners. Patients with cochlear implants can best detect temporal modulation at modulation frequencies below 300 Hz, and are most sensitive to 80- to 100-Hz modulation. At high carrier levels many implant patients could detect smaller modulation amplitudes than normal-hearing listeners, a finding that is consistent with the smaller intensity DLs for some implanted listeners at high levels. These results demonstrate that, while implant listeners cannot discriminate steady-state, high-frequency stimuli, speech information might be conveyed by the envelope of the high-frequency components of speech. PMID- 1597607 TI - Relationships between duration and temporal variability in children's speech. AB - Various studies of speech production development have observed that duration and temporal variability tend to decrease as children get older. Because both of these factors are commonly viewed as general indicators of neuromotor maturation of children's speech skills, it would seem reasonable to assume that they should be rather closely correlated with one another. However, an examination of a variety of temporal data from children ranging between approximately 2 1/2 and 9 1/2 years of age indicates that there is not necessarily as close a correspondence between these two variables as might be expected. It also appears that children's duration measures tend to be more adultlike than measures of their intrasubject variability. PMID- 1597608 TI - Articulatory and social factors influence the acoustic structure of rhesus monkey vocalizations: a learned mode of production? AB - This report presents results that show that the acoustic structure of the "coo" vocalization of rhesus macaques (Macaca mulatta) varies between members of different matrilines. In the case examined, members of one matriline produce coos that are acoustically distinctive from all other matrilines and the difference is primarily due to spectral dampening and the presence of energy bands between the primary harmonics of the call. Perceptually, these acoustic modifications lead to what human listeners hear as a "nasal" utterance, suggesting the possibility of supralaryngeal filtering. Moreover, because nasal-sounding coos were only produced by members of one matriline, learning may be the primary cause of such intrafamilial similarities. PMID- 1597609 TI - Perception of structured phantom targets in the echolocating bat, Megaderma lyra. AB - Bats can discriminate among objects with different texture using echolocation. The mechanisms involved in texture discrimination are unknown. In real echoes reflected from three-dimensional objects, the spatial structure of the target creates a specific temporal and spectral pattern. In the experiments described here, simply structured phantom targets mimicking echoes reflected from an object with two parallel planes were generated by adding two differentially delayed copies of the bat's vocalizations. The discrimination performance of Megaderma lyra was studied in a two-alternative, forced-choice experiment using phantom targets with different internal delays and relative amplitudes of the two copies. When the reference target to which the bats were trained was presented, targets differing in internal delay by about 1 microseconds were discriminated. However, discrimination performance was not a globally monotonic function of the internal delay of the unrewarded target. When both targets presented in a trial differed from the reference, the bats still preferred one of them. Changes in overall level of the phantom target echo had little effect on performance; however, performance dropped considerably if only one of the two copies in an echo was attenuated. A model framework is introduced to account for these results. Models based on frequency processing yield better approximations than does a model based on time differences. The model based on spectral correlation gives a unified description of all the data. Although time domain models for texture discrimination cannot be generally refuted, the results presented here show that the discrimination of target surface structure can be explained as a discrimination of echo spectra. PMID- 1597610 TI - Comparison of the acoustic properties of six popular stethoscopes. AB - This study evaluated stethoscope acoustics by using a sound frequency generator and an active artificial ear. Six popular, currently available stethoscopes were compared in their various modes involving bells, diaphragms, etc.: Littmann Classic II, Littmann Cardiology II, Littmann Master Cardiology, Hewlett-Packard Rappaport-Sprague, Tycos Harvey Triple Head, and Allen Medical Series 5A RPS Binaural. The transfer function was measured from 37.5-1000 Hz, the range where nearly all heart and lung sounds are found. Sound in the low-frequency range (37.5-112.5 Hz) was in most cases amplified by the bells and attenuated by the diaphragms; however, there were no significant differences. Both bells and diaphragms attenuated sound transmission in the high range, and this increased with frequency. The Tycos Harvey Triple Head ribbed diaphragm attenuated sound transmission to a significantly greater extent than the other diaphragms (P less than 0.01). The results show that the bell and diaphragm for a given stethoscope usually have different transmission characteristics, particularly at low frequencies. The Littmann Classic II is an exception. The Hewlett-Packard and Tycos Harvey stethoscopes showed the greatest differences in low frequency response between the bell and the diaphragm. While the differences found in sound transmission between stethoscopes were in most cases small, the Littmann Cardiology II, bell and diaphragm, appears to possess the best overall performance by this study design. PMID- 1597611 TI - Two-sensor power measurements in lossy ducts. AB - Theory and measurements of the use of two adjacent pressure sensors to measure acoustic power flow of a simple harmonic sound wave in a duct are presented. This theory differs from the usual intensity-times-area formulation of this problem by including the phase shift between pressure gradient and velocity, which is caused by viscous drag on the gas at the duct wall. For high standing-wave ratios, the power obtained by this method differs significantly from the product of mid-duct intensity and duct area. These measurements confirm the method to an accuracy of 5%, even at high amplitudes where the acoustic flow is turbulent and the theory might not necessarily be valid. PMID- 1597612 TI - On using coherence to measure distortion in hearing aids. AB - Coherence is a frequency-domain measure of the degree to which the output of a system is linearly related to the system input. The signal-to-distortion ratio (SDR), where the distortion term includes all nonlinear effects and noise in the system, can be computed from the coherence. The coherence estimate, however, is subject to sources of variance and bias that reduce the accuracy of the measured SDR. The origins of the variance and bias and their effects on distortion measurements are presented. New procedures for reducing the variance and bias effects are described, and the processing effectiveness is demonstrated for a simulated hearing-aid response. PMID- 1597613 TI - Rectangular parallelepiped resonance--a technique of resonance ultrasound and its applications to the determination of elasticity at high temperatures. AB - The experimental work on resonance ultrasound, especially using the technique called rectangular parallelepiped resonance (RPR) is reviewed and summarized. The work on high-temperature (at temperatures beyond the Debye temperature) measurements of elastic constants is emphasized. Several applications of this high temperature work are described, including thermal equations of state, the determination of thermodynamic functions, and the determination of the bulk modulus at temperatures beyond experimental capability. PMID- 1597614 TI - Optimal design of an electret microphone metal-oxide-semiconductor field-effect transistor preamplifier. AB - A theoretical noise analysis of the combination of a capacitive microphone and a preamplifier containing a metal-oxide-semiconductor field-effect transistor (MOSFET) and a high-value resistive bias element is given. It is found that the output signal-to-noise ratio for a source follower and for a common-source circuit is almost the same. It is also shown that the output noise can be reduced by making the microphone capacitance as well as the bias resistor as large as possible, and furthermore by keeping the parasitic gate capacitances as low as possible and finally by using an optimum value for the gate area of the MOSFET. The main noise source is the thermal noise of the gate leakage resistance of the MOSFET. It is also shown that short-channel MOSFETs produce more thermal channel noise than longer channel devices. PMID- 1597615 TI - An acoustical study of Korean monophthongs produced by male and female speakers. PMID- 1597616 TI - Reference equivalent threshold levels for the Handtronix, Oto-Screener. PMID- 1597617 TI - License revoked for removing dental amalgam. PMID- 1597618 TI - Patient in Sargenti case gets new trial. PMID- 1597619 TI - OSHA. PMID- 1597620 TI - Cost of OSHA regulations. PMID- 1597621 TI - Whitening. PMID- 1597622 TI - ADA prepares strategy to counter OSHA regs. PMID- 1597623 TI - FDA urges removal of proplast implants. PMID- 1597624 TI - Florida Dental Board investigating hygienists' use of lasers. PMID- 1597625 TI - Evaluating a microfill posterior composite resin. A five-year study. AB - This study evaluates a pre-polymerized microfill composite resin. Results show this particular resin is resistant to generalized wear in conservative restorations. PMID- 1597626 TI - What will the future bring. PMID- 1597627 TI - Managing dentin hypersensitivity: what treatment to recommend to patients. AB - Dentin hypersensitivity affects nearly 40 million Americans at one time or another. The authors outline its causes and describe treatment agents and procedures. PMID- 1597629 TI - How to remain up to date and stimulated with dentistry. PMID- 1597628 TI - Porcelain CAD-CAM veneers. Some new uses explored. AB - With a new CAD-CAM technique, we restored and provided esthetic treatment for both natural teeth and fixed prostheses with worn or broken surfaces. PMID- 1597631 TI - Dental office visits: high-risk behavior? PMID- 1597630 TI - Improving patient appearance. A look at adjunct maxillofacial soft tissue surgery. AB - Adjunctive esthetic procedures, performed with the more traditional oral and maxillofacial surgery, can improve patients' total facial appearance. Three examples illustrate dramatic improvements. PMID- 1597632 TI - The power of leadership: how to make it work for you. PMID- 1597633 TI - Lichen planus and oral cancer: is there a connection between the two? AB - Oral lichen planus has been regarded as a condition with potential for malignant transformation. Critical evaluation of carcinoma cases arising in purported LP shows findings that raise several questions about the accuracy of initial LP diagnoses. PMID- 1597634 TI - Employee performance problems: how to resolve them the right way. PMID- 1597635 TI - Employee benefits. How they affect staff turnover. PMID- 1597636 TI - Benzoic acid and benzoin. PMID- 1597637 TI - Dental implants. PMID- 1597638 TI - Treating HIV patients may cost $10 billion by '94. PMID- 1597640 TI - Achieving the optimal perio-esthetic results: the team approach. AB - Traditional periodontal treatment focused on eradicating disease but gave less consideration to the ideal esthetic relationship of periodontal supporting tissue to the teeth and face. The "perio-esthetic" approach to treatment looks at health, beauty and function as equal elements in determining treatment. It fosters communication and understanding between the general dentist, periodontist and patient. PMID- 1597639 TI - Gazing into the future of esthetic restorative materials. AB - This article outlines the authors' perceptions of the future of esthetic dental restorative materials such as composites, glass ionomer cements, pit and fissure sealants and laboratory fabricated resin. PMID- 1597641 TI - Glass ionomers and esthetic dentistry: what the new properties mean to dentistry. AB - Ingenuity in research and development of glass ionomer systems has slowly but surely improved their handling properties and appearance. The author reviews the latest developments in relation to esthetic dentistry. PMID- 1597642 TI - A glimpse into the 21st century. PMID- 1597643 TI - Preventing dental caries: current and prospective strategies. AB - Strategies of caries prevention can be directed at the resistance of the host/teeth, at the diet, at the microflora or all three. The appropriate preventive interventions depend on the level of caries risk. PMID- 1597644 TI - Treating the pregnant dental patient: four basic rules addressed. PMID- 1597645 TI - Dental care for the elderly. A call for affordable service. PMID- 1597647 TI - The future of dentistry? Treatment shifts to the older adult. PMID- 1597646 TI - Tongue ulcerated by trauma: report of case. AB - A patient's nocturnal tongue biting resulted in a traumatic ulcer on the lateral border of the tongue. The ulcer resolved after a fractured restoration was repaired and topical triamcinolone was applied. PMID- 1597648 TI - What's your MOD net margin? How to monitor, control practice costs. PMID- 1597649 TI - Managing local anesthesia problems in the endodontic patient. AB - Root canal therapy has a poor public image related to occasional and sometimes severe pain, and to dentists' inability to obtain profound anesthesia. Patients' apprehension, in combination with tissue inflammation, significantly lowers the pain threshold, which decreases the anesthetic's effectiveness. The best and also the first approach to achieving anesthesia is to administer a conventional block or infiltration. If profound anesthesia does not occur after this attempt, use a supplemental technique such as lingual infiltrations, PDL or intrapulpal injections. Because infiltrations are generally not effective, PDL and intrapulpal injections are preferred. The PDL is better than the intrapulpal injection because it is non-painful, safe and usually effective. The intrapulpal injection is limited and may be uncomfortable. Administer both the PDL and intrapulpal injections under back-pressure to achieve effective, but short-lived anesthesia. Special injection devices (for example, pressure syringes for the PDL) are not required for either technique. Two anesthetic types are useful. Administer 2 percent lidocaine with epinephrine for conventional and supplemental injections. For emergencies and long procedures, administer 0.5 percent bupivacaine with epinephrine to provide effective, long-lasting anesthesia and analgesia. PMID- 1597650 TI - Immunomodulatory activity of a novel nucleoside, 7-thia-8-oxoguanosine: I. Activation of natural killer cells in mice. AB - We reported recently that a novel immunomodulator, 7-thia-8-oxoguanosine (7T8OG)2 inhibited formation of pulmonary melanoma metastases (1), prevented against viral infection in mice (2) and potentiated the efficacy of a weakly immunogenic leukemia vaccine (3). Since certain tumor metastases and virus infected cells are targets to natural killer cells (NK cells), we now investigated whether 7T8OG is capable of activating NK cells in mice using NK cell sensitive YAC-1 and B16 and NK cell insensitive P815 targets. CBA/CaJ spleen cells incubated in vitro with 7T8OG at concentrations ranging from 0.005 to 0.5 mM responded with increased NK cell activity (32-62%) compared to controls (4-8%) to YAC-1 targets. Similar levels of augmentation in NK cell activity were observed when 40-168 mg/kg of 7T8OG was administered in vivo. In addition to the spleen, 7T8OG activated NK cells in the bone marrow (BM), the lungs, the liver, and in peritoneal exudate cells (PE). Although 7T8OG elicited activation of NK cells was observed as early as three hours after treatment, the maximal activity was observed after 24 h in the spleen; 12 h in the BM; 48 h in the lungs, and 72 h in PE. Administration of the drug by s.c., i.v., and i.p. routes all induced activation of NK cells in spleen, BM and PE. 7T8OG was found to activate NK cells in seven inbred and an outbred mouse strain, suggesting that the induced cytotoxicity against allogeneic and syngeneic tumor cells is not strain specific as well as independent of MHC restriction. C3H/He, CBA/CaJ and BDF/1 displayed higher levels of increased NK cell activity, whereas AKR mice were low responders. Low concentrations of IL-2 (0.25-5 U/ml) that induce little or no NK cell activity, when used in combination with 7T8OG, elicited significant enhancement of NK cell cytotoxicity. In contrast, IFN and 7T8OG showed no such synergism. PMID- 1597651 TI - Induction of immune rejection of tumors by protein A in mice bearing transplantable solid tissue Dalton's lymphoma tumors. AB - In a transplantable solid tissue Dalton's lymphoma tumor model in mice we have studied the mode of antitumor action of protein A, a well known biological response modifier. Protein A (15 ug) was administered intravenously in normal and solid tissue Dalton's lymphoma tumor bearing mice on day 3 and 7 after tumor inoculation. Incidence of mortality was more in untreated tumor bearing group than that in PA treated tumor bearers. There was a significant decrease (p less than 0.001) in tumor diameter in PA treated group compared to untreated group. Protein A treatment significantly enhanced the delayed type hypersensitivity (p less than 0.01), T-cell number in spleens (p less than 0.001) and lymph nodes (p less than 0.05) as well as phagocytosis (p less than 0.001) of opsonized SRBC by peritoneal macrophages of tumor bearing animals. Apart from the nonspecific immunopotentiation, Protein A also activates natural Killer (NK) cell activity and also splenic lymphocytes mediated killing of autologous tumor targets in a significant (p less than 0.001) manner. These results suggest that PA treatment activates cellular arc of the immune system in general, and macrophage, T cells and NK cells specifically. In the present communication, we have attempted to provide the information that these immune activations appear to be related to antitumor response induced by Protein A. PMID- 1597652 TI - The effect of the synthetic lecithin analogue, dimethyl-DL-2, 3 distearolyoxypropyl-2'hydroxylethylammonium acetate, on cytolytic T lymphocyte (CTL) activity. AB - The effect of the synthetic lecithin analogue, dimethyl-DL-2, 3 distearolyoxypropyl-2'hydroxylethylammonium acetate, on CTL cytolytic activity was studied. The analogue significantly inhibits H-2b anti H-2d cytolytic T lymphocytes at concentrations which do not impair lymphocyte viability, protein synthesis, or RNA synthesis. At these concentrations the inhibition is reversible upon removing the analogue. Thus, the inhibition produced by analogue simply is not a result of analogue toxicity. At higher concentrations of the analogue, CTL inhibition is very pronounced; however at these higher concentrations there is evidence of non-specific toxicity of the analogue on CTL. PMID- 1597653 TI - Therapeutic response of chronic active hepatitis B (CAHB) to a new immunomodulator: AM3. Immunohematological effects. AB - AM3, a biological response modifier (BRM) of polysaccharide/protein nature, was given by the oral route to 13 patients with chronic active hepatitis B (CAHB). After 12 months of daily treatment, 8 patients cleared serum HBV-DNA and HBeAg together with ALT normalization. Immunohaematologic studies showed how time of inhibition of viral replication was related to significant decreases of CD4, CD8 and B cell blood lymphocytes. After serum viral elimination, however, a significant haematologic rebound of peripheral blood mononuclear cells (PMNC): CD3, CD4 and CD8 lymphocytes was seen. These data, suggest that the antiviral activities of AM3 may be due to its immunodulatory capacities. These promising results, together with the absence of any side effects, justify the entry to trials with a larger number of patients. Furthermore, treatment with AM3 may help to elucidate the pathophysiology of CAHB. PMID- 1597654 TI - Augmentation of host resistance to Listeria monocytogenes infection by a traditional Chinese medicine, ren-shen-yang-rong-tang (Japanese name: ninjin youei-to). AB - Ren-shen-yang-rong-tang (Japanese name: Ninjin-youei-to, NIN), a traditional Chinese medicine, is a drug made of spray-dried powder of hot water extract obtained from twelve species of medical plants. An intraperitoneal (ip) injection with NIN 2 days before intravenous (iv) infection with Listeria monocytogenes (L. monocytogenes) accelerated elimination of viable bacteria in the spleen in the early stage of infection (from day 1) and protected mice from the lethal infection. It was suggested that the protective effect of NIN was mediated by the activation of nonimmune macrophages playing a principle role in resistance in the early stage of infection. Two days after ip injection with NIN just before infection, significantly increment in the number of monocytes in the peripheral blood was observed, though macrophage number in the spleen and their intracellular killing activity were unchanged. At 12 hours after infection with L. monocytogenes, a significantly enhanced increase of splenic macrophage number was observed in NIN-treated mice, compared to controls. After ip injection of NIN, interleukin-1 (IL-1), IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) became detectable in the serum or peritoneal cavity. These results suggested that NIN stimulated macrophage-precursor cells in the bone marrow via the production of IL-1, IL-6, GM-CSF by macrophages, accelerated the supply of peripheral macrophages, and such macrophages accumulated into the site of infection in the very early stage of infection. Similar protective effects of NIN were observed by oral administration for 7 days till 1 day before iv infection with L. monocytogenes. PMID- 1597655 TI - Anti-asialo GM1 antibodies prevents guanethidine-induced sympathectomy in athymic rats. AB - Guanethidine sulphate induces destruction of peripheral sympathetic neurons and infiltration of mononuclear cells in rat sympathetic ganglia. The effect of guanethidine is believed to be an autoimmune reaction. In order to determine the effect of anti-asialo GM1, an antibody that binds to the glycolipid asialo GM1 expressed on rodent natural killer cells, athymic Lewis rats received guanethidine 40 mg/kg i.p. daily from day 1 to 14 and anti-asialo GM1 i.p. 1 mg/rat on day -2, 0, 2, 6, and 10 in the study period. Saline and anti-asialo GM1 were given alone in the same doses as control. The number of neurons in the sympathetic ganglia were counted and the ganglionic volume determined. The presence of natural killer cells in the ganglia were determined by immunohistochemical methods. Our results shows that anti-asialo GM1 can prevent guanethidine-induced reduction of sympathetic neurons, but not prevent the initiation of an immunological reaction in the ganglia. Natural killer cells could only be identified in ganglia following guanethidine treatment alone. It is concluded that anti-asialo GM1 treatment can prevent the guanethidine-induced sympathectomy by eliminating the natural killer cells from the ganglia. PMID- 1597657 TI - Toxic effects of antiepileptic drugs on immunoglobulin gene expression. AB - Murine myeloma cells were exposed to toxic, growth-retarding levels of two antiepileptic drugs (AEDs2), phenytoin (PHT) and carbamazepine (CBZ). J558L cells were treated for 12 days, washed free of drug and, upon recovery of growth, cloned to determine the frequency of lambda light chain secreting lines. Our results indicate that short-term exposure to high, toxic levels (5-10 times the therapeutic dose) of PHT and CBZ reduces or eliminates lambda light chain secretion at a high frequency. Furthermore, although most cloned lines tested positive for cytoplasmic lambda light chain, some lines had no detectable cytoplasmic immunoglobulin (Ig). The data are consistent with the hypothesis that long-term changes in fully differentiated B cell function may occur after toxic level AED exposure. PMID- 1597656 TI - The effects of volatile anaesthetic agents on human immune system function via occupational exposure. AB - The immunological status of individuals occupationally exposed to low levels of halothane and nitrous oxide has been examined and compared with that of non exposed controls. No differences in the serum concentrations of IgG, IgM, IgA, peripheral blood lymphocytes and lymphocyte subpopulations between the groups were observed. PMID- 1597658 TI - Mitogenic effect of zinc on lymphocytes from strains of mice that are either high or low-responder to T-cell mitogens. AB - We have studied the in vitro mitogenic effect of ZnCl2 in cultures of lymphocytes from Balb/c or C57BL/6 mice which are high-responder or low-responder to T-cell mitogens respectively. Zn induced proliferation of spleen cells from Balb/c mice cultured without 2-ME. Higher levels of proliferation were observed in cultures with 2-ME. In contrast, Zn only induced proliferation of spleen cells from C57BL/6 mice in the presence of 2-ME. No response to Zn was observed in cultures without 2-ME, of spleen cells from either Balb/c or C57BL/6 mice depleted of plastic adherent cells. However, in cultures with 2-ME, Zn induced proliferation of non-adherent as well as plastic adherent cells from either strain of mice. In cultures without 2-ME, Zn induced proliferation of thymocytes from Balb/c mice, whereas did not show constant mitogenic effect on thymocytes from C57BL/6 mice. In contrast, Zn determined higher levels of proliferation of thymocytes from either strain of mice when cultured with 2-ME. Zn had earlier and stronger mitogenic effect on mature thymocytes of either strain of mice than in total thymocytes, both in cultures with or without 2-ME. However, Zn did not induced proliferation in cultures of immature thymocytes of either strain of mice. PMID- 1597659 TI - Protecting effects of vasoactive intestinal polypeptide on lymphocytes against metal toxicity. AB - The hormonal neuropeptides calcitonin gene-related peptide (CGRP), cholecystokinin (CCK), neuropeptide Y (NPY) and vasoactive intestinal peptide (VIP), were investigated for a potential protective effect on thymocytes after a toxic dose of nickel sulfate, giving an inhibition of DNA synthesis. There was a statistically significant increase in the synthesis of DNA from the level caused by nickel sulfate, with VIP, 10(-4)-10(-5) mol/l, while the slightly stimulating effects obtained with CGRP, CCK and NPY, were statistically non-significant. This indicates that VIP, at least as pharmacological concentrations, might have protective effects on lymphocytes against metal toxicity. PMID- 1597661 TI - The impact of acemannan on the generation and function of cytotoxic T lymphocytes. AB - Acemannan, an antiviral agent with immune enhancement capabilities, was studied for its impact on cytotoxic T-lymphocyte (Tc) function generated in response to alloantigen. To investigate whether acemannan directly stimulated the generation of Tc from primary mixed lymphocyte cultures (MLC), the drug was added at the initiation of the MLC. There was a dose-related, statistical increase in killer T cell generation produced by acemannan in the clinically relevant dose range. The lowest test dose of the drug (2.6 x 10(-9) M) increased chromium release nearly two-fold; the 2.6 x 10(-8) M dose gave a maximal 3.5 fold increase in cytotoxic T cells. To study whether acemannan enhanced the capacity of Tc once generated to alloantigen to destroy targets bearing the sensitizing antigens, MLR were established in the absence of any drug. Acemannan at the two highest doses increased the functional capacity of Tc to destroy target cells to which they had been sensitized in the MLR. To control for the possibility that acemannan was directly cytotoxic to target cells, targets were incubated alone with drug and without sensitized killer T-cells. No dose of acemannan was found to be cytotoxic to these cells. In conclusion, acemannan did enhance the generation of cytotoxic T-cells when added at the initiation of the MLR. When acemannan was added at the completion of allostimulation, an increase of almost 50% killing by Tc was also observed. These effects can not be explained by direct drug related toxicity and suggest a functional correlate to the previously described immune enhancing properties of the agent. As this drug is being tested for the treatment of HIV infections, these data provide at least one immunologic mechanism by which acemannan may be clinically salutory. PMID- 1597660 TI - Effect of Bifidobacterium bifidum and Lactobacillus acidophilus on gut mucosa and peripheral blood B lymphocytes. AB - In 15 elderly individuals lyophilized Bifidobacterium bifidum (BB) and Lactobacillus acidophilus (LA) (Infloran) were administered in capsules (two capsules 4 times per day) for 28 days, while in 10 elderly controls placebo were given the same posology and for an equal period of time. The effects of this treatment on the immune system both at the periphery or the intestinal level were investigated. Results show that BB and LA significantly reduced the colonic inflammatory infiltration, without altering T, B and Leu7 + cell percentage. At the same time, a significant increase of B cell frequency in the peripheral blood was noted, in comparison to controls. The overall results suggest that the regular administration of BB and LA leads to a modulation of the immunological and inflammatory response in elderly subjects. PMID- 1597662 TI - Protein A potentiates lymphokine-activated killer cell induction in normal and melanoma patient lymphocytes. AB - The effects of purified protein A from Staphylococcus aureus Cowan I stain on induction of lymphokine (IL-2) activated killer (LAK) activity were studied in normal as well as melanoma patient's lymphocyte. The coculture of peripheral blood mononuclear cells (PBMC) with various doses of protein A (0.001, 0.01 and 0.1 microgram/ml) and IL-2 (100 U/ml) for 4 days produced synergistic effect on the LAK cells mediated cytotoxicity. The potentiation of cytotoxicity and lytic ability of LAK cells against NK sensitive (K-562) and NK-resistant (M14) tumor cells were observed. Further there was potentiation of DNA synthesis in PBMC after 4 days culture. Similar results were found when PBMC from melanoma patients were cultured with PA and IL-2. The potentiation of LAK cell induction associated with its cytotoxic and lytic potential by low doses of IL-2/PA regiment may be helpful in the development of LAK immunotherapy of the cancer patients. PMID- 1597663 TI - Invisible light. AB - Although light is usually thought of in terms of illumination, it is more appropriately defined as electromagnetic radiation. Ultraviolet light, the shorter wavelength, has been suspected for many years as a factor involved in human cataract formation. The effects of ultraviolet light on the lens appear to be similar to age related changes, resulting in earlier formation of cataracts. Since the effects of ultraviolet light are cumulative over the lifespan, eye protection is an essential component of ophthalmic patient education, especially for children and aphakic patients. PMID- 1597664 TI - Mastering communication. PMID- 1597665 TI - Fireworks and eye injuries. PMID- 1597667 TI - Team work: a "vital sign" for success. PMID- 1597666 TI - Teamwork in the ophthalmic office. AB - The ophthalmic office staff consists of a team of professional, technical, and clerical personnel. Each employee needs commitment to achieving optimal care for each patient. Each staff member plays an important role contributing to total patient care. PMID- 1597668 TI - An explanation. PMID- 1597669 TI - Thoughts on ophthalmic nursing and ASORN. PMID- 1597670 TI - Case management: managing financial and clinical outcomes in ophthalmic nursing. AB - Case management is emerging in nursing as an effective and cost efficient model of care delivery for patients with complex nursing, medical, and psychosocial needs. The term "case management" first appeared in the social welfare literature in the early seventies and then later appeared in nursing literature (ANA, 1988). Nursing's concept of case management has been defined and interpreted to fit various health care settings. The purpose of this paper is to address a case management model and demonstrate through a case study how the case management model benefits the patient, the health care team, and the health care agency. PMID- 1597671 TI - Violence: a major public health problem. PMID- 1597672 TI - Impaired physicians: the Kentucky experience. AB - Since 1976 the Committee on Impaired Physicians of the Kentucky Medical Association has become involved with 134 physicians. Most were referred because of possible substance abuse. These physicians represent a wide range of ages and specialties. The Committee typically follows approximately 35 physicians at any given time. Many recover from their problem and are able to return to practice. However, the Committee is aware of only a minority of the impaired physicians that might exist in Kentucky. To be more effective and to reach more impaired physicians, the Committee will need to expand its mission and obtain more resources. PMID- 1597673 TI - Amyloidosis: current approaches for diagnosis and treatment. AB - Amyloidosis is a complex disease resulting from the extracellular deposition of fibrous degradation proteins in body tissues. The type of protein deposited determines the class of amyloidosis present. Morphological, cytochemical, and immunohistochemical studies allow one to precisely identify the class of amyloid present and, therefore, more appropriately select a therapy. Rectal biopsy is the preferred initial procedure for obtaining tissue for study; however, subcutaneous fat pad, gingival, skin, and bone marrow biopsies are alternative noninvasive biopsy sites. We have presented two patients with multiple myeloma and amyloidosis of the AL type. One patient presented with multi-organ failure of undetermined etiology and the other with asymptomatic hepatosplenomegaly. The diagnosis of amyloidosis was made by bone marrow biopsy in the first patient and rectal biopsy in the second patient using morphological studies and confirmed cytochemically with the congo red stain. The type of amyloidosis was determined with immunohistochemical studies. Their clinical course and response to therapy will be assessed by repeated immunoglobulin studies, liver and spleen size, and studies for organ dysfunction such as 2-D echo and level of proteinuria. PMID- 1597675 TI - An historical perspective of the mental illness of Vincent Van Gogh. PMID- 1597674 TI - The Ilizarov method (callus distraction) in the treatment of open fractures of the tibia. AB - The treatment of bone defects, in particular open fractures of the tibia, represents a significant health care concern for physicians and surgeons in the Commonwealth. Traditional methods of treatment, including those that utilize internal and/or external fixation devices, often have drawbacks. The Ilizarov method (callus distraction), which combines acute shortening with subsequent lengthening using an external ring fixator, offers a new approach to treating bone defects. The authors describe the Ilizarov method, discuss Ilizarov's research and his development of the callus distraction technique, and review the growing body of English-language literature assessing the use of the Ilizarov method. PMID- 1597676 TI - Voltage-dependent and odorant-regulated currents in isolated olfactory receptor neurons of the channel catfish. AB - The electrical properties of olfactory receptor neurons, enzymatically dissociated from the channel catfish (Ictalurus punctatus), were studied using the whole-cell patch-clamp technique. Six voltage-dependent ionic currents were isolated. Transient inward currents (0.1-1.7 nA) were observed in response to depolarizing voltage steps from a holding potential of -80 mV in all neurons examined. They activated between -70 and -50 mV and were blocked by addition of 1 microM tetrodotoxin (TTX) to the bath or by replacing Na+ in the bath with N methyl-D-glucamine and were classified as Na+ currents. Sustained inward currents, observed in most neurons examined when Na+ inward currents were blocked with TTX and outward currents were blocked by replacing K+ in the pipette solution with Cs+ and by addition of 10 mM Ba2+ to the bath, activated between 40 and -30 mV, reached a peak at 0 mV, and were blocked by 5 microM nimodipine. These currents were classified as L-type Ca2+ currents. Large, slowly activating outward currents that were blocked by simultaneous replacement of K+ in the pipette with Cs+ and addition of Ba2+ to the bath were observed in all olfactory neurons examined. The outward K+ currents activated over approximately the same range as the Na+ currents (-60 to -50 mV), but the Na+ currents were larger at the normal resting potential of the neurons (-45 +/- 11 mV, mean +/- SD, n = 52). Four different types of K+ currents could be differentiated: a Ca(2+)-activated K+ current, a transient K+ current, a delayed rectifier K+ current, and an inward rectifier K+ current. Spontaneous action potentials of varying amplitude were sometimes observed in the cell-attached recording configuration. Action potentials were not observed in whole-cell recordings with normal internal solution (K+ = 100 mM) in the pipette, but frequently appeared when K+ was reduced to 85 mM. These observations suggest that the membrane potential and action potential amplitude of catfish olfactory neurons are significantly affected by the activity of single channels due to the high input resistance (6.6 +/- 5.2 G omega, n = 20) and low membrane capacitance (2.1 +/- 1.1 pF, n = 46) of the cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597677 TI - Intramembrane charge movements in frog skeletal muscle in strongly hypertonic solutions. AB - Intramembrane charge movements were studied in intact, voltage-clamped frog (Rana temporaria) skeletal muscle fibers in external solutions made increasingly hypertonic by addition of sucrose. The marked dependence of membrane capacitance on test potential persisted with increases in extracellular sucrose concentration between 350 and 500 mM. Charge movements continued to show distinguishable early monotonic (q beta) decays and the strongly voltage-dependent delayed (q gamma) charging phases reported on earlier occasions. In contrast, a further increase to 600 mM sucrose abolished the most steeply voltage-sensitive part of the membrane capacitance. It left a more gradual variation with potential that closely resembled the function that resulted when q gamma charge was abolished by tetracaine in the presence of 500 mM sucrose. Charging transients were now simple monotonic (q beta) decays and lacked delayed (q gamma) transients. Furthermore, tetracaine (2 mM) altered neither the kinetic nor the steady-state features of the charge left in 600 mM sucrose. However, Ca2+ current activation in the same fibers persisted through such tonicity increases under identical conditions of temperature, external solution, and holding voltage. Tonicity changes thus accomplish an independent separation of q gamma and q beta charge as defined hitherto through their tetracaine sensitivity. Their effects on q gamma charge correlate with earlier observations of osmotic conditions on delta[Ca2+] signals (1987. J. Physiol. (Lond.) 383:615-627.) and the parallel effects of other agents on excitation-contraction coupling and q gamma charge. In contrast, they suggest that Ca2+ current activation does not require q gamma charge transfer whether by itself or as part of the excitation-contraction coupling process. PMID- 1597678 TI - Tris+/Na+ permeability ratios of nicotinic acetylcholine receptors are reduced by mutations near the intracellular end of the M2 region. AB - Tris+/Na+ permeability ratios were measured from shifts in the biionic reversal potentials of the macroscopic ACh-induced currents for 3 wild-type (WT), 1 hybrid, 2 subunit-deficient, and 25 mutant nicotinic receptors expressed in Xenopus oocytes. At two positions near the putative intracellular end of M2, 2' (alpha Thr244, beta Gly255, gamma Thr253, delta Ser258) and -1', point mutations reduced the relative Tris+ permeability of the mouse receptor as much as threefold. Comparable mutations at several other positions had no effects on relative Tris+ permeability. Mutations in delta had a greater effect on relative Tris+ permeability than did comparable mutations in gamma; omission of the mouse delta subunit (delta 0 receptor) or replacement of mouse delta with Xenopus delta dramatically reduced relative Tris+ permeability. The WT mouse muscle receptor (alpha beta gamma delta) had a higher relative permeability to Tris+ than the wild-type Torpedo receptor. Analysis of the data show that (a) changes in the Tris+/Na+ permeability ratio produced by mutations correlate better with the hydrophobicity of the amino acid residues in M2 than with their volume; and (b) the mole-fraction dependence of the reversal potential in mixed Na+/Tris+ solutions is approximately consistent with the Goldman-Hodgkin-Katz voltage equation. The results suggest that the main ion selectivity filter for large monovalent cations in the ACh receptor channel is the region delimited by positions -1' and 2' near the intracellular end of the M2 helix. PMID- 1597679 TI - Optical measurement of osmotic water transport in cultured cells. Role of glucose transporters. AB - Methodology was developed to measure osmotic water permeability in monolayer cultured cells and applied to examine the proposed role of glucose transporters in the water pathway (1989. Proc. Natl. Acad. Sci. USA. 86:8397-8401). J774 macrophages were grown on glass coverslips and mounted in a channel-type perfusion chamber for rapid fluid exchange without cell detachment. Relative cell volume was measured by 45 degrees light scattering using an inverted microscope; measurement accuracy was validated by confocal imaging microscopy. The time required for greater than 90% fluid exchange was less than 1 s. In response to a decrease in perfusate osmolality from 300 to 210 mosM, cells swelled without lag at an initial rate of 4.5%/s, corresponding to a water permeability coefficient of (6.3 +/- 0.4) x 10(-3) cm/s (SE, n = 20, 23 degrees C), assuming a cell surface-to-volume ratio of 4,400 cm-1. The initial rate of cell swelling was proportional to osmotic gradient size, independent of perfusate viscosity, and increased by amphotericin B (25 micrograms/ml), and had an activation energy of 10.0 +/- 1 kcal/mol (12-39 degrees C). The compounds phloretin (20 microM) and cytochalasin B (2.5 micrograms/ml) inhibited glucose transport by greater than 85% but did not influence Pf in paired experiments in which Pf was measured before and after inhibitor addition. The mercurials HgCl2 (0.1 mM) and p chloromercuribenzoate (1 mM) did not inhibit Pf. A stopped-flow light scattering technique was used to measure Pf independently in J774 macrophages grown in suspension culture. Pf in suspended cells was (4.4 +/- 0.3) x 10(-3) cm/s (assuming a surface-to-volume ratio of 8,800 cm-1), increased more than threefold by amphotericin B, and not inhibited by phloretin and cytochalasin B under conditions of strong inhibition of glucose transport. The glucose reflection coefficient was 0.98 +/- 0.03 as measured by induced osmosis, assuming a unity reflection coefficient for sucrose. These results establish a quantitative method for measurement of osmotic water transport in adherent cultured cells and provide evidence that glucose transporters are not involved in the water transporting pathway. PMID- 1597681 TI - Kinetic analysis of water transport through a single-file pore. AB - We apply the diagrammatic method developed by Hill (1977. Free Energy Transduction in Biology. Academic Press, New York) to analyze single-file water transport. We use this formalism to derive explicit expressions for the osmotic and diffusive permeabilities Pf and Pd of a pore. We first consider a vacancy mechanism of transport analogous to the one-vacancy pore model previously used by Kohler and Heckmann (1979. J. Theor. Biol. 79:381-401). (a) For the general one vacancy case, we find that the permeability ratio can be expressed by Pf/Pd = (Pf/Pd)eqf(wA,wB), where the second factor is a function of the water activities in the two adjoining compartments A and B. As a consequence, the permeability ratio in general can effectively differ from its value at equilibrium. We also find that n - 1 less than or equal to (Pf/Pd)eq less than or equal to n, a result already proposed by Kohler and Heckmann (1979. J. Theor. Biol. 79:381-401). (b) When vacancy states are transient intermediates, the model can be reduced to a diagram consisting of only fully occupied states. Such a diagram resembles the one describing a no-vacancy mechanism of transport (c), but in spite of the similarity the expressions obtained for the permeability coefficients still retain the basic relationships of the original (a) nonreduced one-vacancy model. (c) We then propose a kinetic description of a no-vacancy mechanism of single file water transport. In this case, the expressions derived for Pf and Pd are formally equivalent to those obtained by Finkelstein and Rosenberg (1979. Membrane Transport Processes. Vol. 3. C.F. Stevens and R.W. Tsien, editors, Raven Press, New York. 73-88.) A main difference with the vacancy mechanism is that here the permeability coefficients are independent of the water activities. PMID- 1597682 TI - Report on the 14th annual meeting of the European Neuroscience Association. 8-12 September 1991, Cambridge, UK. PMID- 1597680 TI - Apical K+ channels in Necturus taste cells. Modulation by intracellular factors and taste stimuli. AB - The apically restricted, voltage-dependent K+ conductance of Necturus taste receptor cells was studied using cell-attached, inside-out and outside-out configurations of the patch-clamp recording technique. Patches from the apical membrane typically contained many channels with unitary conductances ranging from 30 to 175 pS in symmetrical K+ solutions. Channel density was so high that unitary currents could be resolved only at negative voltages; at positive voltages patch recordings resembled whole-cell recordings. These multi-channel patches had a small but significant resting conductance that was strongly activated by depolarization. Patch current was highly K+ selective, with a PK/PNa ratio of 28. Patches containing single K+ channels were obtained by allowing the apical membrane to redistribute into the basolateral membrane with time. Two types of K+ channels were observed in isolation. Ca(2+)-dependent channels of large conductance (135-175 pS) were activated in cell-attached patches by strong depolarization, with a half-activation voltage of approximately -10 mV. An ATP blocked K+ channel of 100 pS was activated in cell-attached patches by weak depolarization, with a half-activation voltage of approximately -47 mV. All apical K+ channels were blocked by the sour taste stimulus citric acid directly applied to outside-out and perfused cell-attached patches. The bitter stimulus quinine also blocked all channels when applied directly by altering channel gating to reduce the open probability. When quinine was applied extracellularly only to the membrane outside the patch pipette and also to inside-out patches, it produced a flickery block. Thus, sour and bitter taste stimuli appear to block the same apical K+ channels via different mechanisms to produce depolarizing receptor potentials. PMID- 1597683 TI - German-Austrian Space Occupying Cerebellar Infarction Study (GASCIS): study design, methods, patient characteristics. The Steering and Protocol Commission. AB - An open prospective multicentric therapeutic trial to determine the timing and type of therapeutic intervention in patients presenting with secondary deterioration following cerebellar stroke is described. According to the results of retrospective studies a controlled approach comparing different therapies is ethically not feasible. Participants use the same scores and protocol for patient data collection but many choose different therapeutic procedures. PMID- 1597684 TI - Clinical correlates of high signal lesions on magnetic resonance imaging in Alzheimer's disease. AB - The pathophysiology and clinical significance of high signal lesions, visualized on magnetic resonance imaging (MRI) in patients with Alzheimer's disease (AD), remain controversial. Since they are known to correlate with vascular disease and vascular risk factors, we reviewed the clinical correlates of periventricular high signal (PVH) and subcortical white matter lesions (WML) in a sample of 106 patients with probable AD, excluding persons with treated vascular risk factors or symptomatic cerebrovascular and cardiovascular disease. Grade 2 PVH were seen in 26 (25%) and scattered WML were identified in 29 (18%). PHV were associated with advancing age and gait disturbance. WML were associated with gait disturbance and incontinence. Neither radiologic finding was related to dementia severity. The findings suggest that these lesions are common in patients with AD even when those with evidence of cerebrovascular disease are excluded; their presence, therefore, should not preclude a diagnosis of AD. Additionally, the data suggest that HSL on MRI may be one of many risk factors associated with functional disability in persons with probable AD. PMID- 1597685 TI - Ultrastructural and immunohistochemical study of degenerate neurite-bearing ghost tangles. AB - Some ghost tangles in the brains of Alzheimer patients were accompanied by many small argyrophilic structures which were electron microscopically confirmed to be degenerate neurites. In these ghost tangles, roughly dispersed 15 nm straight and occasional twisted tubules were penetrated by proliferated astrocytic processes. Immunohistochemically, these ghost tangles lost immunoreactivities to anti-NFT, tau and -ubiquitin antibodies, but were thioflavine-S fluorescent, though antigenicity to beta-protein was not proved. This similarity in composition of degenerate neurite-bearing ghost tangles to senile plaques might be induced by the amyloid nature of tubules, which probably provokes the reaction of neuropils. PMID- 1597687 TI - Primary orthostatic tremor: further observations in six cases. AB - The clinical and physiological features of six new patients with primary orthostatic tremor are described. We suggest that use of the term primary orthostatic tremor be confined to the clinical syndrome in which unsteadiness when standing is the predominant complaint and accompanied by characteristic electrophysiological findings of a rapid (frequency around 16 Hz), regular leg tremor which is not influenced by peripheral feedback, is synchronous between homologous leg muscles, and in certain postures of the upper limbs, between muscles of the arm and leg. The fast frequency of muscle activity in primary orthostatic tremor of the legs causes unsteadiness when standing (presumably due to partially fused muscle contraction) but only a fine ripple of muscle activity is visible. In contrast, the slower frequency of other leg tremors, for example essential tremor, results in obvious leg movement which is evident in many leg postures, is variable over time and can be reset by a peripheral nerve stimulus. Essential tremor and orthostatic tremor do not respond to the same therapies, suggesting differences in the pharmacological profiles of the two conditions. Accordingly, there are clinical, physiological and pharmacological differences between primary orthostatic and essential tremor. Whether these factors are sufficient to regard these tremors as separate conditions is discussed. PMID- 1597686 TI - The clinical significance of sleep apnoea in workers exposed to organic solvents: implications for the diagnosis of organic solvent encephalopathy. AB - Among 51 patients referred for investigation of possible organic solvent encephalopathy 20 (39%) had pathological sleep apnoea [apnoea index (AI) greater than 5], compared with 5 of 16 house painters exposed to solvents (31%) who were screened for the disorder, and 1 of 18 (6%) age-matched controls. Twelve of the patients with AI greater than 5 were retested after 2 or more weeks without exposure to solvents, and showed a significant drop in AI. Likewise, significantly lower AI was seen in patients who were no longer exposed to solvents, compared with recently exposed patients. The implications of these findings for diagnostic evaluation of solvent encephalopathy and sleep apnoea are discussed. PMID- 1597688 TI - Neurophysiological evaluation of sensorimotor functions of the leg: comparison of evoked cortical potentials following electrical and mechanical stimulation, long latency muscle responses, and transcranial magnetic stimulation. AB - Twenty-two patients with localized lesions of the central nervous system (unilateral cerebral ischaemia, cervical myelopathy, spinal tumour, familial spastic paraplegia) underwent neurophysiological evaluation of sensorimotor deficits of the leg. Functional methods using muscle stretch as stimulus, i.e. long-latency muscle responses and cortical potentials evoked by dorsiflection of the foot, were compared with transcranial magnetic stimulation and somatosensory evoked cortical potentials following electrical stimulation of the posterior tibial nerve. The functional neurophysiological methods yielded no diagnostic superiority with respect to the procedures using artificial (i.e. magnetic and electrical) stimulation. However, in most cases of missing compound motor action potentials following transcranial magnetic stimulation or missing electrically evoked cortical potentials, the long-latency muscle responses still allowed quantitative assessment of sensorimotor function. PMID- 1597689 TI - Speech deficits in ischaemic cerebellar lesions. AB - Twelve patients with cerebellar infarction, 8 in the region supplied by the posterior inferior cerebellar artery (PICA) and 4 in the territory of the superior cerebellar artery, underwent formal perceptual examination for speech deficits. With respect to topography the results firstly underline the significance of the paravermal region of the superior cerebellar portion for speech functions. In all patients with dysarthric impairment the lesion extended to this area, whereas patients with PICA infarction sparing the superior portion of the cerebellum showed no speech deficits. Secondly the findings do not corroborate the notion of an exclusively left-sided cerebellar speech motor control, since 3 of the 4 dysarthric subjects had unilateral right-sided ischaemia. This study thirdly demonstrates that lesions of the cerebellar cortex without involvement of the dentate nucleus can cause dysarthric impairment. Phonetic analysis revealed irregularly distributed articulatory deficits and slowed speech tempo as the most common dysarthric features. PMID- 1597690 TI - Palatal myoclonus occurring during complex partial status epilepticus. AB - Palatal myoclonus is thought to occur after damage to certain brain-stem structures, and with a delay following the causative lesion. A case of palatal myoclonus, probably of epileptic nature, is described. PMID- 1597691 TI - Tonic pupil, areflexia, and segmental anhidrosis: two additional cases of Ross syndrome and review of the literature. AB - Two patients are described with the triad of tonic pupil, hyporeflexia and segmental anhidrosis (Ross syndrome). Only 18 cases of this syndrome have been reported in the literature so far. While tonic pupil and reduced sweating can be attributed to the affection of postganglionic cholinergic parasympathetic and sympathetic fibres projecting to the iris and sweat glands, respectively, the pathogenesis of diminished or lost tendon jerks remains obscure. To identify the characteristic clinical features, the previous cases of Ross syndrome are reviewed. Recent evidence of subclinical disturbances of sweating in most patients with Adie's syndrome, i.e. tonic pupil and areflexia, casts doubt on the nosological concept of Ross syndrome as a distinct clinical entity. PMID- 1597692 TI - Cholesterol levels in circulating immune complexes in patients with carotid artery stenosis. PMID- 1597693 TI - An international comparison of dietary protein consumption and mortality from Parkinson's disease. PMID- 1597694 TI - Purkinje cell antibodies in a patient with cerebellar disorder. PMID- 1597695 TI - Progressive improvement in discriminative abilities in adult owl monkeys performing a tactile frequency discrimination task. AB - 1. Adult owl monkeys were trained to detect a difference in the frequency of sequentially applied tactile stimuli presented to a constant, restricted location on the glabrous skin of a single finger. Psychophysical performance functions and thresholds were determined on daily sessions over a 3- to 20-wk-long training period. 2. Thresholds for the trained digit progressively decreased from a 6- to 8-Hz difference to a 2- to 3-Hz difference relative to a 20-Hz standard. These thresholds were similar to those described for macaques and humans determined by the use of a two-alternative forced-choice procedure. 3. Six of the seven studied monkeys showed a continuously progressive improvement in performance with training. Early in the training period, the performance improved at about the same rate for all frequencies. Later in the training period, the performance for frequencies much greater than the comparison frequency improved sooner than did the performances for frequencies more similar to the comparison frequency. This resulted in an increase of the slope of the psychometric function near threshold. In a single monkey, no clear later-component improvements were recorded. 4. Analyses of performances using the theory of signal detection revealed a progressive increase in the measure of d' for all frequencies above threshold. 5. Some improvements in performance were also recorded when stimuli were applied on an adjacent digit, which was trained for 2 or 3 sessions spaced throughout the course of training. However, thresholds on these digits were always greater than those on the trained digit. These findings suggest that there are local changes generated by this training at somatotopically restricted regions of the central somatosensory nervous system. 6. It is concluded that this training resulted in a genuine progressive improvement in temporal acuity specific to the trained skin. The initial rapid improvement was likely due to an improvement in the "strategy" or "cognitive" aspects of the task, whereas more gradual improvements in performance recorded throughout the training period were most probably due to somatotopically localized changes in the neural representations of the behaviorally relevant stimulus. PMID- 1597696 TI - Topographic reorganization of the hand representation in cortical area 3b owl monkeys trained in a frequency-discrimination task. AB - 1. Adult owl monkeys were trained to detect differences in the frequency of a tactile flutter-vibration stimulus above a 20-Hz standard. All stimuli were delivered to a constant skin site restricted to a small part of a segment of one finger. The frequency-difference discrimination performance of all but one of these monkeys improved progressively with training. 2. The distributed responses of cortical neurons ("maps") of the hand surfaces were defined in detail in somatosensory cortical area 3b. Representations of trained hands were compared with those of the opposite, untrained hand, and to the area 3b representations of hands in a second set of monkeys that were stimulated tactually in the same manner while these monkeys were attending to auditory stimuli (passive stimulation controls). 3. The cortical representations of the trained hands were substantially more complex in topographic detail than the representations of unstimulated hands or of passively stimulated control hands. 4. In all well trained monkeys the representations of the restricted skin location trained in the behavioral task were significantly (1.5 to greater than 3 times) greater in area than were the representations of equivalent skin locations on control digits. However, the overall extents of the representations of behaviorally stimulated fingers were not larger than those of control fingers in the same hemisphere, or in opposite hemisphere controls. 5. The receptive fields representing the trained skin were significantly larger than receptive fields representing control digits in all but one trained monkey. The largest receptive fields were centered in the zone of representation of the behaviorally engaged skin, but they were not limited to it. Large receptive fields were recorded in a 1- to 2-mm-wide zone in the area 3b maps of trained hands. 6. Receptive-field sizes were also statistically significantly larger on at least one adjacent, untrained digit when compared with the receptive fields recorded on the homologous digit of the opposite hand. 7. There was an increase in the percent overlaps of receptive fields in the cortical zone of representation of the trained skin. A significant number of receptive fields were centered on the behaviorally trained skin site. 8. The effects of increased topographic complexity, increased representation of the trained skin location, increased receptive-field size, and increased receptive-field overlap were not observed in the representations of the untrained hands in these same monkeys. Only modest increases in topographic complexity were recorded in the representations of passively stimulated hands, and no effects on receptive-field size or overlap were noted.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597697 TI - Frequency discrimination training engaging a restricted skin surface results in an emergence of a cutaneous response zone in cortical area 3a. AB - 1. The responses of cortical neurons evoked by cutaneous stimulation were investigated in the hand representation of cortical area 3a in adult owl monkeys that had been trained in a tactile frequency discrimination task. Cortical representations of the hands in these experimental hemispheres were compared with those representing the opposite, untrained hand, as well as with those representing a passively stimulated hand in a second class of control monkeys. 2. A large cutaneous representation of the hairy and glabrous skin surfaces of the hand emerged in area 3a in each trained hemisphere. 3. With the emergence of cutaneous responses recorded for neurons at many area 3a locations, the normally recorded deep receptor inputs were no longer evident at most of these locations. 4. There was a greater territory of representation of the small area of skin that was stimulated in the behavioral task in trained monkeys, when compared with the representations of corresponding skin sites in the opposite hemisphere of the same monkeys, or to the representations of equivalent skin sites stimulated in passively stimulated control monkeys. 5. There was great variability in the receptive-field properties of neurons responsive to cutaneous inputs among trained monkeys. In most recording sites within the representations of the behaviorally engaged hands, the cutaneous receptive fields were large, extending over a significant part of the glabrous or hairy surfaces of the hand. However, in one monkey, very small, topographically ordered cutaneous receptive fields were recorded over a wide zone of area 3a. 6. The physiologically defined borders between areas 3a and 3b were in register with the cytoarchitectonically defined borders between these two cortical areas in trained and in control monkeys. 7. This study demonstrates that there is a reorganization of the cutaneous and "deep" representation of hand in cortical area 3a, with the main change being an emergence of a large cutaneous representation and the parallel disappearance of a large part of the normal deep representation in this field. These changes are discussed in light of the possible functional roles of cortical area 3a. PMID- 1597698 TI - Changes in the distributed temporal response properties of SI cortical neurons reflect improvements in performance on a temporally based tactile discrimination task. AB - 1. Temporal response characteristics of neurons were sampled in fine spatial grain throughout the hand representations in cortical areas 3a and 3b in adult owl monkeys. These monkeys had been trained to detect small differences in tactile stimulus frequencies in the range of 20-30 Hz. Stimuli were presented to an invariant, restricted spot on a single digit. 2. The absolute numbers of cortical locations and the cortical area over which neurons showed entrained frequency-following responses to behaviorally important stimuli were significantly greater when stimulation was applied to the trained skin, as compared with stimulation on an adjacent control digit, or at corresponding skin sites in passively stimulated control animals. 3. Representational maps defined with sinusoidal stimuli were not identical to maps defined with just-visible tapping stimuli. Receptive-field/frequency-following response site mismatches were recorded in every trained monkey. Mismatches were less frequently recorded in the representations of control skin surfaces. 4. At cortical locations with entrained responses, neither the absolute firing rates of neurons nor the degree of the entrainment of the response were correlated with behavioral discrimination performance. 5. All area 3b cortical locations with entrained responses evoked by stimulation at trained or untrained skin sites were combined to create population peristimulus time and cycle histograms. In all cases, stimulation of the trained skin resulted in 1) larger-amplitude responses, 2) peak responses earlier in the stimulus cycle, and 3) temporally sharper responses, than did stimulation applied to control skin sites. 6. The sharpening of the response of cortical area 3b neurons relative to the period of the stimulus could be accounted for by a large subpopulation of neurons that had highly coherent responses. 7. Analysis of cycle histograms for area 3b neuron responses revealed that the decreased variance in the representation of each stimulus cycle could account for behaviorally measured frequency discrimination performance. A strong correlation between these temporal response distributions and the discriminative performances for stimuli applied at all studied skin surfaces was even stronger (r = 0.98) if only the rising phases of cycle histogram were considered in the analysis. 8. The responses of neurons in area 3a could not account for measured differences in frequency discrimination performance. 9. These representational changes did not occur in monkeys that were stimulated on the same schedule but were performing an auditory discrimination task during skin stimulation. 10. It is concluded that by behaviorally training adult owl monkeys to discriminate the temporal features of a tactile stimulus, distributed spatial and temporal response properties of cortical neurons are altered.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597699 TI - Knee joint input into the peripheral region of the ventral posterior lateral nucleus of cat thalamus. AB - 1. Experiments were carried out in chloralose-anesthetized cats to study the responses of neurons in the lateral thalamus to excitation of afferent fibres from the knee joint. 2. Single- and multi-unit recordings were made with tungsten electrodes in dorsoventral penetrations through the ventral posterior lateral nucleus (VPL) during electrical stimulation of the medial articular nerve (MAN) of the cat's knee joint at an intensity sufficient to excite slowly conducting unmyelinated fibers. The locations of the recording sites were verified by recovering electrolytic lesion sites in histological sections (Nissl and cytochrome oxidase staining). 3. The average earliest latency for excitation of thalamic responses was 19.1 +/- 8.5 (SD) ms (n = 50). The threshold for excitation of most thalamic units was found to correspond to peripheral joint afferent fibers of the A-delta group. 4. The majority of neurons responding to MAN stimulation were found to be dorsal or ventral to the low-threshold cutaneous hindlimb region of the lateral division of the VPL (stereotaxic coordinates: AP 9.0-11.5; ML 7.0-9.5). In the ventral periphery of the VPL, most neurons responding to MAN stimulation (11/14) were wide dynamic range (WDR) with a discrete cutaneous receptive field on the hindpaw digits. Six WDR neurons were found dorsal to the hindlimb VPL with a convergent receptive field on the hindlimb (but not hindpaw digits). No nociceptive-specific knee joint units were found. 5. Other neurons were found dorsal to the hindlimb VPL with large receptive fields often encompassing the whole contralateral leg, including skin and deep hindlimb structures, possibly in a region described as the dorsal portion of the posterior complex (POd). Some neurons were found with no receptive field. 6. This study provides the first observations on the responses of lateral thalamic neurons to stimulation of the MAN of the cat knee joint. These results demonstrate a central pathway conveying impulses from specific deep joint afferents of the MAN to the peripheral region of the VPL and overlying region known as the POd, regions implicated in the transmission of nociceptive information. PMID- 1597701 TI - Strength increases from the motor program: comparison of training with maximal voluntary and imagined muscle contractions. AB - 1. This study addressed potential neural mechanisms of the strength increase that occur before muscle hypertrophy. In particular we examined whether such strength increases may result from training-induced changes in voluntary motor programs. We compared the maximal voluntary force production after a training program of repetitive maximal isometric muscle contractions with force output after a training program that did not involve repetitive activation of muscle; that is, after mental training. 2. Subjects trained their left hypothenar muscles for 4 wk, five sessions per week. One group produced repeated maximal isometric contractions of the abductor muscles of the fifth digit's metacarpophalangeal joint. A second group imagined producing these same, effortful isometric contractions. A third group did not train their fifth digit. Maximal abduction force, flexion/extension force and electrically evoked twitch force (abduction) of the fifth digit were measured along with maximal integrated electromyograms (EMG) of the hypothenar muscles from both hands before and after training. 3. Average abduction force of the left fifth digit increased 22% for the Imagining group and 30% for the Contraction group. The mean increase for the Control group was 3.7%. 4. The maximal abduction force of the right (untrained) fifth digit increased significantly in both the Imagining and Contraction groups after training (10 and 14%, respectively), but not in the Control group (2.3%). These results are consistent with previous studies of training effects on contralateral limbs. 5. The abduction twitch force evoked by supramaximal electrical stimulations of the ulnar nerve was unchanged in all three groups after training, consistent with an absence of muscle hypertrophy. The maximal force of the left great toe extensors for individual subjects remained unchanged after training, which argues against strength increases due to general increases in effort level. 6. Increases in abduction and flexion forces of the fifth digit were poorly correlated in subjects of both training groups. The fifth finger abduction force and the hypothenar integrated EMG increases were not well correlated in these subjects either. Together these results indicate that training-induced changes of synergist and antagonist muscle activation patterns may have contributed to force increases in some of the subjects. 7. Strength increases can be achieved without repeated muscle activation. These force gains appear to result from practice effects on central motor programming/planning. The results of these experiments add to existing evidence for the neural origin of strength increases that occur before muscle hypertrophy. PMID- 1597700 TI - Quantitative analysis of static strain sensitivity in human mechanoreceptors from hairy skin. AB - 1. Microelectrode recordings from 15 slowly adapting (SA) cutaneous mechanoreceptor afferents originating in hairy skin were obtained from the radial nerve in humans. 2. Controlled skin stretch was applied to the back of the hand that encompassed the physiological range of skin stretch during movements at the metacarpophalangeal (MCP) joints. 3. Both SA Group I and II afferents showed exquisite dynamic and static sensitivity to skin stretch. The median static strain sensitivity was 1.0 imp.s-1 per percent skin stretch for SAI units and 1.8 for SAII units. 4. Translated into sensitivity to movements at the MCP joint, both SAI and SAII afferents in the skin of the back of the hand displayed a positional sensitivity that was comparable with that reported for muscle spindle afferents. 5. These data give quantitative support to suggestions that skin receptors in the human hairy skin provide information on nearby joint configurations and therefore may play a specific role in proprioception, kinesthesia, and motor control. PMID- 1597703 TI - Velocity of shortening of single motor units from rat soleus. AB - 1. The force-velocity relationship of a motor unit can provide insight into the contractile proteins of its constituent fibers as well as fundamental information about the function and use of the motor unit. Although the force-velocity profiles of whole muscle and skinned mammalian fibers have been studied, technical difficulties have prevented similar studies on motor units. A technique is presented to directly measure the velocity of shortening of individual motor units from in vivo rat soleus muscle. 2. The soleus muscles of anesthetized rats were dissected free of surrounding tissue while their nerve and blood supplies were preserved. Both tendons were cut, and the distal tendon was attached to a servomechanism to control muscle length, whereas the proximal tendon was attached to a force transducer. Single motor units were stimulated via the ventral roots. 3. The major problem encountered in measuring the force-velocity profile of a motor unit was that the force from the large number of passive fibers and connective tissue in the soleus confounded the force produced by the small number of active fibers in the motor unit. This problem was minimized by measuring active motor unit tension during an isovelocity ramp. This allowed experimental measurement of the passive tension by shortening the muscle with an identical isovelocity ramp without, however, stimulating the motor unit. Active tension was estimated by subtracting the passive tension waveform from the waveform recorded when the motor unit was active. 4. The method substantially reduced the noise from the passive fibers; however, problems remained. The probable sources of error are discussed, with the most significant being the elasticity associated with the blood and nerve connections to surrounding tissue. The elasticity prevents uniform shortening velocities along the length of the active fibers, thereby introducing a systematic bias to measurements made at high velocities. These errors are most pronounced when the data are extrapolated to determine the maximum velocity of shortening (Vmax). Determination of velocity at peak power (Vpp) is a more robust measure; however, of the 34 motor units studied, only 19 exhibited a distinct peak in the power-force curve, indicating residual noise. 5. To assess the validity of using twitch contraction time as an index of the velocity of shortening, when possible, Vmax and Vpp of each motor unit were correlated with the inverse of its twitch contraction time. The correlation was poor (r less than 0.2), indicating that, although widely used, twitch contraction time is a poor index of contractile speed. PMID- 1597702 TI - Spontaneous nystagmus and gaze-holding ability in monkeys after intravitreal picrotoxin injections. AB - 1. Eye movements were measured in three rhesus monkeys after monocular intravitreal injections of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist. The effects of this drug were tested when the animals were in a completely dark room, when they performed a smooth pursuit task, and when they viewed either a stationary pattern or a full-field optokinetic pattern rotating horizontally. 2. Between 15 and 20 min after the injection, a sustained conjugate spontaneous nystagmus developed in the dark, with the slow-phase movement in the temporal-to-nasal direction with respect to the injected eye. Peak slow-phase velocity ranged from 15 to 45 degrees/s. The nystagmus persisted for at least 1 h but stopped by the next day. 3. In a well-lit room, the nystagmus was completely suppressed, even during monocular viewing with the injected eye. When the lights were turned off, the slow-phase velocity of the spontaneous nystagmus slowly increased to a steady-state level within 70-120 s. 4. Horizontal smooth pursuit eye movements to a 1 degree target light moving in front of the animal +/- 20 degrees to either side of center of gaze at constant speeds were normal. Target speeds ranging from 15 to 60 degrees/s for both monocular and binocular viewing conditions were used. Binocular and monocular optokinetic nystagmus (OKN) to a full-field drum rotating at a constant velocity (5-90 degrees/s) were also normal. The initial pursuit and steady-state components of OKN were measured, as well as the velocity-storage component (optokinetic after nystagmus, OKAN).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597704 TI - Stabilization of gaze during circular locomotion in light. I. Compensatory head and eye nystagmus in the running monkey. AB - 1. A rhesus and cynomolgus monkey were trained to run around the perimeter of a circular platform in light. We call this "circular locomotion" because forward motion had an angular component. Head and body velocity in space were recorded with angular rate sensors and eye movements with electrooculography (EOG). From these measurements we derived signals related to the angular velocity of the eyes in the head (Eh), of the head on the body (Hb), of gaze on the body (Gb), of the body in space (Bs), of gaze in space (Gs), and of the gain of gaze (Gb/Bs). 2. The monkeys had continuous compensatory nystagmus of the head and eyes while running, which stabilized Gs during the slow phases. The eyes established and maintained compensatory gaze velocities at the beginning and end of the slow phases. The head contributed to gaze velocity during the middle of the slow phases. Slow phase Gb was as high as 250 degrees/s, and targets were fixed for gaze angles as large as 90-140 degrees. 3. Properties of the visual surround affected both the gain and strategy of gaze compensation in the one monkey tested. Gains of Eh ranged from 0.3 to 1.1 during compensatory gaze nystagmus. Gains of Hb varied around 0.3 (0.2-0.7), building to a maximum as Eh dropped while running past sectors of interest. Consistent with predictions, gaze gains varied from below to above unity, when translational and angular body movements with regard to the target were in opposite or the same directions, respectively. 4. Gaze moved in saccadic shifts in the direction of running during quick phases. Most head quick phases were small, and at times the head only paused during an eye quick phase. Eye quick phases were larger, ranging up to 60 degrees. This is larger than quick phases during passive rotation or saccades made with the head fixed. 5. These data indicate that head and eye nystagmus are natural phenomena that support gaze compensation during locomotion. Despite differential utilization of the head and eyes in various conditions, Gb compensated for Bs. There are various frames of reference in which an estimate of angular velocity that drives the head and eyes could be based. We infer that body in space velocity (Bs) is likely to be represented centrally to provide this signal. PMID- 1597705 TI - Stabilization of gaze during circular locomotion in darkness. II. Contribution of velocity storage to compensatory eye and head nystagmus in the running monkey. AB - 1. Yaw eye in head (Eh) and head on body velocities (Hb) were measured in two monkeys that ran around the perimeter of a circular platform in darkness. The platform was stationary or could be counterrotated to reduce body velocity in space (Bs) while increasing gait velocity on the platform (Bp). The animals were also rotated while seated in a primate chair at eccentric locations to provide linear and angular accelerations similar to those experienced while running. 2. Both animals had head and eye nystagmus while running in darkness during which slow phase gaze velocity on the body (Gb) partially compensated for body velocity in space (Bs). The eyes, driven by the vestibuloocular reflex (VOR), supplied high-frequency characteristics, bringing Gb up to compensatory levels at the beginning and end of the slow phases. The head provided substantial gaze compensation during the slow phases, probably through the vestibulocollic reflex (VCR). Synchronous eye and head quick phases moved gaze in the direction of running. Head movements occurred consistently only when animals were running. This indicates that active body and limb motion may be essential for inducing the head-eye gaze synergy. 3. Gaze compensation was good when running in both directions in one animal and in one direction in the other animal. The animals had long VOR time constants in these directions. The VOR time constant was short to one side in one animal, and it had poor gaze compensation in this direction. Postlocomotory nystagmus was weaker after running in directions with a long VOR time constant than when the animals were passively rotated in darkness. We infer that velocity storage in the vestibular system had been activated to produce continuous Eh and Hb during running and to counteract postrotatory afterresponses. 4. Continuous compensatory gaze nystagmus was not produced by passive eccentric rotation with the head stabilized or free. This indicates that an aspect of active locomotion, most likely somatosensory feedback, was responsible for activating velocity storage. 5. Nystagmus was compared when an animal ran in darkness and in light. the beat frequency of eye and head nystagmus was lower, and the quick phases were larger in darkness. The duration of head and eye quick phases covaried. Eye quick phases were larger when animals ran in darkness than when they were passively rotated. The maximum velocity and duration of eye quick phases were the same in both conditions. 6. The platform was counterrotated under one monkey in darkness while it ran in the direction of its long vestibular time constant.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597706 TI - Hypoglossal neural activity during licking and swallowing in the awake rat. AB - 1. Thirty-five neurons in the hypoglossal nucleus (mXII) of the rat were characterized during licking and swallowing in response to fluid stimulation in an awake, freely moving preparation. Simultaneously recorded electromyographic (EMG) recordings from a subset of oropharyngeal muscles were obtained to delineate both the lick cycle and the occurrence of swallows. Most mXII neurons discharged with rhythmic bursts in phase with licking. Twenty-six of the 35 mXII neurons had bimodal interspike interval (ISI) histograms, reflecting rhythmic bursts and the absence of spontaneous activity. Three mXII cells with unimodal ISI histograms were rhythmically active during licking but had some spontaneous activity. Of the remaining six cells with unimodal ISI histograms, five had nonbursting modes of activity. 2. Phase relationships between neural and EMG activity during licking were determined by cross-correlation and compared with distributions of cross-correlations between lingual and masticatory EMG activity. A bimodal distribution of cross-correlations was obtained by cross-correlating EMG activity between lingual protrudor muscles [genioglossus (GG) or geniohyoid (GH)] and masticatory jaw-opener activity [anterior digastric (AD)] and cross correlating lingual retractor activity [styloglossus (STY)] with anterior digastric EMG. A similar bimodal distribution of cross-correlations obtained between mXII neuron activity and AD contractions suggested that the majority of mXII neurons (30/35) could be classified as protrudor- or retractor-related. Neurons classified as protrudor-related cells were located ventrally in mXII; cells classified as retractor-related were more dorsally located, consistent with anatomic and physiological descriptions of the myotopic organization of mXII. 3. Ten mXII protrudor-related neurons responded with a mean of 4.9 +/- 2.2 (SD) action potentials per lick cycle and preceded the peak jaw-opening phase of licking by a mean of 22.3 ms. In contrast, the activity of 20 retractor-related mXII neurons lagged the jaw-opening phase of licking by a mean of 55.9 ms, with a mean of 5.5 +/- 3.4 (SD) action potentials occurring per lick cycle. Five other mXII neurons exhibited nonrhythmic activity during licking and could not be classified as protrudor- or retractor-related on the basis of cross-correlations with the AD. 4. The occurrence of a swallow decreased the licking frequency by 21%, corresponding to an increase of approximately 43 ms in the period between AD contractions.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597707 TI - Effects of ganglionic satellite cells and NGF on the expression of nicotinic acetylcholine currents by rat sensory neurons. AB - 1. We have investigated two factors that affect the expression of nicotinic acetylcholine (ACh) currents on neonatal rat sensory neurons: an influence derived from ganglionic satellite cells, and nerve growth factor (NGF). 2. With the use of whole-cell patch-clamp techniques on rat nodose neurons, we have measured the proportion of neurons sensitive to ACh and have quantified their ACh current densities. The majority (60%) of nodose neurons from neonatal animals do not express nicotinic acetylcholine receptors (nAChRs); the remaining 40% had ACh current densities that ranged from 0.4 to 93 pA/pF. Furthermore, neither the proportion nor the ACh current densities change over the first two postnatal weeks in vivo. 3. The expression of ACh currents by these neurons in vivo is controlled, in part, by an influence from the ganglionic satellite cells: culturing neurons in the absence of other cell types results in an increase in the proportion of ACh-sensitive neurons, whereas coculturing neurons with their satellite cells maintains functional nAChR expression in its in vivo state. Furthermore, satellite cells are not required continually, as a brief exposure to this influence, either in vivo or in culture, is sufficient to exert its effect on functional nAChR expression. 4. On removal of this satellite cell influence, the neurons respond to NGF treatment by increasing their ACh current densities: the median ACh current density for neurons grown for 2-3 wk with NGF was 32.5 pA/pF, whereas, the median ACh current density for neurons cultured without NGF for the same time was 4.5 pA/pF.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597708 TI - Cholinergic suppression specific to intrinsic not afferent fiber synapses in rat piriform (olfactory) cortex. AB - 1. Differences in the cholinergic suppression of afferent and intrinsic fiber synaptic transmission were studied in the rat piriform cortex. Extracellular and intracellular recording techniques were applied in an in vitro transverse slice preparation. Afferent and intrinsic fiber systems were differentially stimulated with electrodes placed in layer Ia or layer Ib, respectively. Synaptic responses were monitored in the presence of cholinergic agonists and antagonists. 2. Afferent and intrinsic fiber synaptic potentials measured extracellularly showed large differences in sensitivity to micromolar concentrations of the cholinergic agonists carbachol or (+/-)-muscarine, or to acetylcholine combined with neostigmine. Intrinsic fiber synaptic responses in layer Ib were strongly reduced in the presence of cholinergic agonists, whereas afferent fiber synaptic responses in layer Ia were largely unaffected. At a concentration of 100 microM, all three agonists caused a greater than 60% decrease in the height of the intrinsic fiber synaptic potential but less than 15% reduction in the afferent fiber synaptic potential. 3. Intracellular recordings confirmed that the cholinergic agonist carbachol selectively suppresses intrinsic fiber synaptic potentials but not afferent fiber synaptic potentials recorded from the same pyramidal cell. 4. Dose-response curves to carbachol were obtained for both fiber systems using extracellular recording of evoked field potentials. Carbachol suppressed intrinsic fiber synaptic potentials with a coefficient of dissociation (KD) estimated at 2.9 microM and an inhibitory concentration for 50% response estimated at 6.6 microM. 5. Carbachol produced a proportionately greater suppression of the first pulse than the second pulse of a pulse pair. This increase in the level of facilitation accompanying suppression suggests a presynaptic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597710 TI - Analysis of temporal discharge characteristics of dorsal cochlear nucleus neurons of unanesthetized decerebrate cats. AB - 1. We examined the mean and standard deviation (SD) of interspike intervals (ISI) and the coefficient of variation (CV, the ratio of SD of ISI to mean ISI) of ISIs versus time to study discharge regularity of units in the dorsal cochlear nucleus (DCN) of decerebrate unanesthetized cats. The units were characterized by the use of both poststimulus time histograms (PSTH) and excitatory-inhibitory area (EI area) schemes. We present results of a systematic examination of all of 87 DCN pause-build units recorded in this study. In addition, we present examples of chopper subtypes of the DCN. 2. A major finding of this study is that a majority of the pause-build units in the present sample exhibited regular discharges in response to short (50 ms) tone bursts at characteristic frequency (CF), as revealed by CVs less than 0.5. A predominant portion of pause-build units (80% of 44 units with sufficient number of spikes for CV analysis) exhibited mean CVs less than 0.5 in the 20- to 39.9-ms time window in response to 50-ms tone burst at CF at 60 dB SPL re 20 microPa; 39% of the 44 units exhibited highly regular discharges (mean CV less than 0.35). During the onset (2-14.9 ms) time window, 77% (of 53 units with sufficient number of spikes for CV analysis) of the units had mean CVs less than 0.5, and 55% were less than 0.35. 3. In our sample of 87 DCN pause-build units, 59% had spontaneous rates (SR) greater than 15 spikes/s. The pause-build units of the present sample were distributed across four different EI-area types: III (51%), I/III (25%), II (15%), or IV (9%). In the 20- to 39.9-ms time window, the pause-build units with mean CVs less than 0.35 were exclusively of types III and I/III. All of the above EI-area types were represented in the lowest CV group for the 2- to 14.9-ms window. 4. The mean ISIs of DCN pause-build units typically showed a decrease during the first 20-25 ms of the response to 50-ms CF tone bursts, and stable mean ISIs in the latter half, when off-discharges were absent. In the presence of off-discharges, the mean ISIs decreased further in the last 5-10 ms of the response.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597709 TI - Cholinergic modulation of cortical associative memory function. AB - 1. The effect of cholinergic modulation on associative memory function was studied in a computational model based on the physiology and anatomic structure of piriform cortex. Both the cholinergic suppression of intrinsic fiber synaptic transmission and the cholinergic changes in postsynaptic excitability described in the companion paper were examined. 2. Distributed input patterns representing odors were stored in the model with the use of a synaptic modification rule dependent on pre- and postsynaptic activity (i.e., Hebbian). Associative recall of these patterns was tested by presenting the model with degraded versions of the learned patterns and testing whether these degraded patterns evoked the same network response as the full learned input pattern. Storage was evaluated with the use of a performance measure designed to reflect how well degraded input patterns could be recognized as a particular learned input pattern. 3. When memory function was evaluated with a selective cholinergic suppression of intrinsic fiber synaptic transmission during learning, associative memory performance was greatly enhanced. Cholinergic suppression during learning prevents previously stored patterns from interfering with the storage of new patterns. 4. When memory function was evaluated with a cholinergic mediated enhancement in cell excitability during learning, the speed of learning increased, but so did the decay in performance due to interference during learning. 5. When suppression of intrinsic fiber synaptic transmission was coupled with an increase in cell excitability, the best memory performance was obtained. 6. These results provide a possible theoretical framework for linking the neuropharmacological effects of acetylcholine to behavioral evidence for a role of acetylcholine in memory function. This could help describe how memory deficits might arise from cholinergic dysfunction in diseases such as Alzheimer's dementia. PMID- 1597711 TI - Kinematics of typing: parallel control of the two hands. AB - 1. Experienced touch typists were asked to type words in which only a single letter was typed by one hand, while the remaining letters were typed with the other hand. 2. Translational and rotational motion of each finger was computed optoelectronically from the location of reflective markers. Translational and rotational motion of both wrists was also computed from the locations of these markers. 3. Typically, when a subject typed a single letter, all of the fingers of the hand were in motion, as was the wrist. For each letter, this overall kinematic pattern of finger and wrist motion was highly repeatable. Thus the keystroke kinematics formed a repeatable signature for a particular letter typed by a particular subject. 4. During the keystroke the other hand was also in motion, typing the preceding and succeeding letters. During this period the motion of the two wrists and the motions of corresponding fingers of both hands was uncorrelated. 5. Because the keystroke kinematics are highly repeatable and independent of the movement of the contralateral hand, each keystroke represents a fundamental element of the typing movement. Thus these results provide a basis for determining the processes whereby sequences of keystrokes are assembled to type words. PMID- 1597712 TI - Organization of sequential typing movements. AB - 1. Experienced touch typists were asked to type words that contained only one or two letters typed by one of the two hands. When a word contained a pair of letters typed by one hand, the letters could be consecutive, or there could be one, two, or three intervening letters typed with the other hand. 2. We studied cases in which pairs of letters were either identical, different but typed with the same finger, or typed with two different fingers on the same hand. 3. Translational and rotational motion of the fingers and wrist was computed optoelectronically from the location of reflective markers on the hands. Finger and wrist motion recorded when subjects typed pairs of letters was compared with the motion recorded when the subject typed either letter in isolation. 4. When the subject typed the same letter consecutively, or separated by intervening letters, the second keystroke began only after the first key had been pressed. The same result was obtained when the second letter was not identical but was typed with the same finger. Up to the time of the first keypress, the initial keystroke kinematics were identical to those for that letter typed in isolation. 5. When the second letter in a pair was typed with the use of a different finger, the initial focal movement (wrist and finger striking the key) was unaffected up to the time of initial keypress. However, the second finger could begin to move toward the second key shortly before the initial keypress, and therefore the corollary movements normally involved in the initial keystroke were affected. 6. These results indicate that typing movements are executed primarily in a serial fashion, letter by letter. There can be some overlap between consecutive keystrokes only if they are executed with different fingers. 7. Words in which two letters typed with one hand were separated by three letters typed with the other hand provided subjects the opportunity to initiate the second keystroke at a range of times after the first keypress. 8. When the second letter differed from the first, subjects always returned to the home position after the first keypress and initiated the second keystroke with a normal latency. However, when the second letter was the same as the first letter, subjects sometimes suppressed the return to the home position after the first keystroke and maintained their finger poised over the key. 9. Thus keystrokes of one hand are best described as being executed sequentially. However, the findings presented here also indicate that movement planning encompasses strings of letters. PMID- 1597713 TI - Postnatal development of voltage-gated K currents on rat sympathetic neurons. AB - 1. We have investigated the developmental expression of three voltage-gated K currents on neonatal rat superior cervical ganglion (SCG) neurons in vivo and in culture: a rapidly inactivating current (IAf), a slowly inactivating current (IAs), and a noninactivating current (IK). 2. On postnatal day 1 neurons (P1), mean peak IAs is 67 +/- 4 (SE) pA/pF, peak IAf is 27 +/- 3 pA/pF, and IK is 14 +/ 3 pA/pF. Over the next wk, there is a switch in the expression of these currents: IAs drops by 40%, whereas IAf increases by greater than 100%; there is no change in IK. On P14 neurons, IAs is 38 +/- 2 pA/pF, IAf is 64 +/- 5 pA/pF, and IK is 12 +/- 1 pA/pF. 3. The change in expression of K currents on SCG neurons over the first 2 postnatal wk is unaffected by preganglionic innervation or by innervation of the targets. 4. To learn more about the factors that affect K current expression on these neurons, we grew SCG neurons in culture without other cell types for various times, and we measured the expression of IAf, IAs, and IK. In culture, the currents remained at their P1 levels for the first 4-7 days. Thereafter, both IAs and IAf decreased to low levels over a period of 2-3 wk. These results suggest that an epigenetic factor(s) is necessary for the expression of IAf and IAf in vivo and that this factor is missing in culture. 5. When IAs and IAf decreased on neurons in culture, we observed a compensatory increase in IK. After 4 wk in culture, IK is fourfold greater than on neurons in vivo. This result suggests that these neurons have intrinsic mechanisms that coordinate the expression of different voltage-gated K currents. PMID- 1597714 TI - Ionic currents of morphologically distinct peptidergic neurons in defined culture. AB - 1. The X-organ sinus gland is a major peptidergic neurosecretory system in Crustacea, analogous to the vertebrate hypothalamoneurohypophyseal system. Neuronal somata isolated from the crab (Cardisoma carnifex) X-organ and maintained in primary culture in unconditioned, fully defined medium show immediate regenerative outgrowth. Outgrowth occurring as broad lamellipodia ("veiled") distinguishes neurons consistently showing crustacean hyperglycemic hormone immunoreactivity. Neurons that are immunoreactive against molt-inhibiting hormone and red pigment concentrating hormone antisera give rise to branched neurites ("branched"). 2. The whole-cell variation of the patch-clamp technique was used to study the electrophysiology of these two cell types 24-48 h after plating. Under current clamp, only veiled neurons fired overshooting action potentials either spontaneously or in response to depolarization. 3. Under voltage clamp, net current was predominantly outward. When solutions that suppressed outward current were used, only veiled neurons showed significant inward current. These included a tetrodotoxin (TTX)-sensitive Na current and a slow (time to peak 6-10 ms at 0 mV) Cd-sensitive Ca current (ICa) that was activated at potentials less than -30 mV, was maximal at 0 to +20 mV, and did not reverse at potentials up to +60 mV. 4. In TTX, the form of the Ca current I(V) curve was unchanged by changes of holding potential between -40 and -80 mV, and 75-100% of ICa was available from -40 mV. 5. ICa inactivated slowly and incompletely. Analysis with two-pulse regimes suggested that both inactivation and facilitation mechanisms were present. 6. Outward current was examined in the presence and absence of 0.5 mM Cd2+ (1 microM TTX was always present in the external medium). Cd2+ ions slightly reduced the peak outward current, usually by less than 10% (Vc = -10 to +20 mV; Vh = -80 mV). All additional observations were in the presence of TTX and Cd2+. 7. Both cell types expressed a 4-aminopyridine (4-AP)-sensitive transient current, analogous to IA, and a slower-rising (minimum time to peak 20 ms), sustained current that was partially sensitive to tetraethylammonium, analogous to IK. 8. The mean Vh at which IA was half inactivated was -46 mV, and the mean time constant for removal of inactivation was 46 ms.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597715 TI - Intercellular signaling in Necturus taste buds: chemical excitation of receptor cells elicits responses in basal cells. AB - 1. Taste cells in intact taste buds in slices of Necturus lingual epithelium were impaled with microelectrodes for intracellular recording. Two types of cells were investigated: taste receptor cells and basal cells. 2. Impaling cells in the apical end of taste buds resulted in intracellular records from taste receptor cells. Applying short pulses (100- to 200-ms duration) of 140 mM KCl solution to the apical pore elicited receptor potentials in the taste receptor cells. 3. Impaling cells in the base of the taste bud resulted in intracellular records from taste receptor cells and basal cells. KCl applied to the taste pore elicited responses in the basal region that varied greatly in both magnitude and time of onset. The latency of these responses (time of onset compared with the onset of the receptor potential) ranged from 0 to hundreds of milliseconds. 4. Impaled cells were identified by injecting Lucifer yellow after recording KCl responses for 21 cells. KCl responses recorded from identified basal cells all had latencies of greater than 75 ms. KCl responses from identified receptor cells all had latencies of less than 75 ms. 5. One explanation for the long latency of KCl responses recorded in basal cells is that the responses represent postsynaptic potentials. In agreement with this interpretation, long-latency responses, but not short-latency responses, were reversibly reduced by the Ca antagonist Cd (1 mM, 10- to 20-min bath exposure). 6. Long-latency responses also differed from short-latency responses in their voltage dependence. Short-latency responses had the same voltage dependence as apically recorded receptor potentials, increasing with hyperpolarization from resting potential with an extrapolated reversal potential near 0 mV. Long-latency responses were much less dependent on voltage in this range. 7. We measured the spread of exogenously applied KCl with potassium-sensitive electrodes. Long-latency responses were not generated by diffusion of applied KCl to the basal region of the taste bud. A small transient increase in extracellular potassium occurred at the base of the taste bud after chemostimulation at the apical pore. This increase was due to depolarization evoked release of potassium from taste cells and did not cause the long-latency responses in basal cells. 8. We conclude that short-latency (less than 75 ms) responses recorded from cells situated in the bases of taste buds are electrotonically conducted receptor potentials generated at the apical region. Long-latency (greater than 75 ms) responses are consistent with recording postsynaptic responses in basal cells. PMID- 1597716 TI - Properties of reach-related neuronal activity in cortical area 7A. AB - 1. In protocol 1, two macaque monkeys were trained to reach to illuminated buttons with the right arm as reach-related unit activity was monitored in area 7a of the left hemisphere. 2. Of 402 neurons recorded in area 7a, 109 changed their discharge rates during the reach task. The change could occur early or late in the trajectory, or during the return movement of the arm to the rest plate. Spatial preferences were seen in 59/109 reach-related cells, usually for the right or center buttons. 3. In protocol 2, another monkey was trained to reach with either arm to targets displayed on a touch-sensitive video monitor. Of 273 neurons sampled in area 7a (both hemispheres) during the bilateral task performance, 84 were reach-related: 33 responded similarly to reaches of either arm. Most of the rest had a contralateral arm preference. When bilateral reach related cells had a spatial preference, that preference was the same for both arms. 4. With the use of two target sequences in either protocol, it was found that spatial preferences were observable only for primary reaches from the side of the body up to the target. Relatively few cells responded to other trajectories, and those that did usually failed to discriminate movement direction. Movement extent did not influence discharge rates. 5. Although a total of 125/270 reach cells had observable visual responses, only 4 out of 18 cells tested in both dark and light conditions showed a significant drop in reach related activity in the dark. Thus visual input from the moving hand probably is responsible for only part of the reach activity in area 7a. 6. Reach-related activity in area 7a appears to signal specific phases of the motor performance and is often restricted to distinct spatial regions. As such, it could be used by the frontal lobe to facilitate upcoming elements of a motor sequence, including terminal corrections. PMID- 1597717 TI - Membrane properties of dentate gyrus granule cells: comparison of sharp microelectrode and whole-cell recordings. AB - 1. Whole-cell and sharp electrode recordings from adult rat dentate gyrus GCs were performed in the 400-microns-thick hippocampal slice preparation maintained at 34 +/- 1 degrees C. Intrinsic membrane properties of granule cells (GCs) were evaluated with the use of a switching current-clamp amplifier. 2. With the whole cell technique, the average resting membrane potential (RMP) of GCs was -85 mV when a potassium gluconate electrode solution was used versus -74 mV measured with potassium acetate-filled sharp microelectrodes. The membrane voltage response to injected current was linear over two membrane potential ranges, greater than 10 mV hyperpolarized from RMP and between 10 mV more negative than RMP and -62 mV. The average input resistances (RN) calculated over these ranges were 107 and 228 M omega in the whole-cell recordings versus 37 and 54 M omega in the sharp electrode recordings. There was no correlation between RMP and RN with either recording technique. The membrane time constant (tau m) determined at the RMP was 26.9 ms for whole-cell recordings and 13.9 ms for sharp electrode recordings. 3. There was no evidence of time-dependent changes in RMP, RN, and tau m in whole-cell recordings, although the slow inward rectification seen at hyperpolarized potentials decreased over 30-60 min. Addition of calcium buffers to the whole-cell recording solution did not result in a significant change in the average RMP, the average RN, or the average tau m. 4. Action potential threshold was comparable in whole-cell (-49 mV) and sharp electrode (-52 mV) recordings, but action potential amplitude was larger in whole-cell (126 mV) than in sharp electrode (106 mV) recordings. Spike frequency adaptation was present in the whole-cell recordings and could be abolished by addition of calcium buffers to the electrode solution. 5. We estimated rho, the ratio of dendritic to somatic conductance, to be 5.1 for the whole-cell records and 2.1 for sharp electrode recordings. The electrotonic length of the equivalent cylinder representing the cell processes was estimated to be 0.49 from the whole-cell data and 0.79 from the sharp electrode recordings. This implies that at rest there is only a 10% decrement in steady-state membrane voltage along the length of the dendrite due to shunting across the membrane resistance; small synaptic events occurring in the distal dendritic tree will therefore have a more substantial influence on the soma than previous analyses suggested.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597718 TI - Recurrent collaterals of motoneurons projecting to distal muscles in the cat hindlimb. AB - 1. Recurrent collaterals of motoneurons innervating muscles that have a role in control of the hindlimb digits were studied with neuroanatomic tracing methods to determine whether these motoneurons have simple recurrent collateral arbors in comparison with those of hip, knee, and ankle muscles. 2. Motoneurons innervating the hindlimb muscles plantaris (Pln), flexor hallucis longus (FHL), or flexor digitorum longus (FDL) were injected with 10% horseradish peroxidase. Recurrent collaterals were reconstructed from serial transverse sections. 3. No recurrent collaterals were observed in a sample of 10 FDL motoneurons. 4. FHL motoneurons had simple recurrent collateral arbors as assessed by number of first-order collaterals, number of collateral swellings, number of end branches, and the highest-order branch of individual collateral trees. Recurrent collateral arbors of Pln motoneurons were more complex than those of FHL motoneurons. Pln and FHL recurrent collateral arbors were less complex than those described for gastrocnemius-soleus, anterior tibial, and posterior biceps motoneurons. 5. These anatomic findings correspond well with electrophysiological results indicating that the recurrent inhibition produced by FHL motoneurons is weak and that FDL motoneurons do not produce recurrent inhibition. In addition, Pln motoneurons are reported to produce stronger recurrent inhibition than FHL motoneurons in many motor pools. 6. Consideration of these results with respect to the mechanical actions and patterns of motor activity observed in FDL, FHL, and Pln suggests that the complexity of recurrent collaterals of a motoneuron pool and the extent of its contribution to recurrent inhibition diminish with its involvement in the individualized control of the digits. PMID- 1597719 TI - gamma-Aminobutyric acid-induced response in rat dissociated paratracheal ganglion cells. AB - 1. The pharmacologic properties of gamma-aminobutyric acid (GABA)-induced Cl- current (ICl) were studied in the paratracheal ganglion cells freshly dissociated from 7- to 10-day-old rat trachea in a whole-cell recording mode by the use of a conventional patch-clamp technique. 2. GABA- and muscimol-induced currents increased sigmoidally in a concentration-dependent manner, and both currents reversed at approximately -3 mV, which was close to the Cl- equilibrium potential (ECl). 3. Strychnine (STR) at low concentration and bicuculline (BIC) inhibited GABA response competitively, whereas STR at the higher concentrations, benzylpenicillin (PCG), or picrotoxin (PTX) inhibited noncompetitively. Inhibition of GABA response by PCG but not other antagonists was voltage dependent, indicating that PCG acts as a Cl- channel blocker. 4. The concentration-response curve of pentobarbital sodium (PB)-induced ICl was bell shaped. At concentrations higher than 10(-3) M, both the peak and plateau currents decreased, and a transient "hump" current appeared immediately after washing out PB. In the presence of PB, the concentration-response curve of GABA shifted toward left without changing the maximum response. 5. Although diazepam (DZP) at concentration used did not induce a response, it potentiated the GABA response in a concentration-dependent manner between 10(-8) and 10(-6) M. DZP also caused a parallel shift toward left in the concentration-response curve of GABA. 6. PB or DZP further enhanced the GABA response in the presence of the other agent. 7. It is concluded that the properties of GABAA receptors in the paratracheal ganglion cells are essentially similar to those reported in other preparations. PMID- 1597720 TI - Reflex responses in active muscles elicited by stimulation of low-threshold afferents from the human foot. AB - 1. Reflex responses were elicited in muscles that act at the ankle by electrical stimulation of low-threshold afferents from the foot in human subjects who were reclining supine. During steady voluntary contractions, stimulus trains (5 pulses at 300 Hz) were delivered at two intensities to the sural nerve (1.2-4.0 times sensory threshold) or to the posterior tibial nerve (1.1-3.0 times motor threshold for the intrinsic muscles of the foot). Electromyographic (EMG) recordings were made from tibialis anterior (TA), peroneus longus (PL), soleus (SOL), medial gastrocnemius (MG), and lateral gastrocnemius (LG) muscles by the use of intramuscular wire electrodes. 2. As assessed by averages of rectified EMG, stimulation of the sural or posterior tibial nerves at nonpainful levels evoked a complex oscillation with onset latencies as early as 40 ms and lasting up to 200 ms in each muscle. The most common initial responses in TA were a decrease in EMG activity at an onset latency of 54 ms for sural stimuli, and an increase at an onset latency of 49 ms for posterior tibial stimuli. The response of PL to stimulation of the two nerves began with a strong facilitation of 44 ms (sural) and 49 ms (posterior tibial). With SOL, stimulation of both nerves produced early inhibition beginning at 45 and 50 ms, respectively. With both LG and MG, sural stimuli produced an early facilitation at 52-53 ms. However, posterior tibial stimuli produced different initial responses in these two muscles: facilitation in LG at 50 ms and inhibition in MG at 51 ms. 3. Perstimulus time histograms of the discharge of 61 single motor units revealed generally similar reflex responses as in multiunit EMG. However, different reflex components were not equally apparent in the responses of different single motor units: an individual motor unit could respond slightly differently with a change in stimulus intensity or background contraction level. The multiunit EMG record represents a global average that does not necessarily depict the precise pattern of all motor units contributing to the average. 4. When subjects stood erect without support and with eyes closed, reflex patterns were seen only in active muscles, and the patterns were similar to those in the reclining posture. 5. It is concluded that afferents from mechanoreceptors in the sole of the foot have multisynaptic reflex connections with the motoneuron pools innervating the muscles that act at the ankle. When the muscles are active in standing or walking, cutaneous feedback may play a role in modulating motoneuron output and thereby contribute to stabilization of stance and gait. PMID- 1597721 TI - Innervation ratio is an important determinant of force in normal and reinnervated rat tibialis anterior muscles. AB - 1. The technique of glycogen depletion and periodic acid-Schiff (PAS) staining, which identifies glycogen-free muscle fibers, was used to directly count the number (N) and measure the cross-sectional area (CSA) of muscle fibers in single motor units (MUs) from normal and reinnervated tibialis anterior (TA) muscles. Indirect estimates, derived from the proportions of muscle fiber types to MU types, were also made, and force per unit area (or specific force, SF) was calculated. Previous results using direct and indirect approaches have been contradictory. To shed more light on this issue, the relative contributions of N, mean fiber area (A), and SF to muscle-unit force were determined by the use of both methods. 2. TA muscles were examined in experimental rats 3.5-10 mo after cutting and resuturing the common peroneal nerve in one hindlimb and in muscles in age-matched control rats. Ventral roots were dissected to isolate and characterize single MUs according to contraction speed, sag, and fatigability. One unit per muscle was selected for repetitive tetanic stimulation designed to deplete muscle fiber glycogen stores. Muscles were removed for identification of the unit with the PAS reaction and histochemical fiber typing by the use of modified standard techniques. 3. In the total population of MUs sampled, isometric tetanic force ranged from 5 to 441 mN in normal muscles and from 5 to 498 mN in reinnervated muscles, and the mean values were not significantly different. In the smaller sample of glycogen-depleted units from normal muscle, for a force range of 14-217 mN, N varied from 57 to 202, and A varied from 1,135 +/- 45 to 6,706 +/- 172 (SE) microns2. Within each unit the variation in fiber area is broad. After reinnervation, for a force range of 30-278 mN, N varied from 70 to 374, and A varied from 1,694 +/- 81 to 5,425 +/- 93 microns2. Mean fiber number was 153 +/- 18 in reinnervated muscle, which is significantly higher (P less than 0.01) than the normal value of 121 +/- 9. 4. The contribution of N and A to MU tetanic force was assessed by plotting each factor as a function of force on a log-log scale. N accounts for 39% and A for 49% of the variation in force in normal muscle. The contributions are changed after reinnervation where N, accounting for 65% of force, appears to compensate for the reduced range in A, which accounts for only 19% of the variation in force.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597722 TI - Motor-unit categorization based on contractile and histochemical properties: a glycogen depletion analysis of normal and reinnervated rat tibialis anterior muscle. AB - 1. Isolated and glycogen-depleted motor units (MUs) have been studied in normal and reinnervated tibialis anterior (TA) muscles of the rat to examine 1) the correspondence between physiological and histochemical classifications, 2) the extent to which unit properties cluster according to type, 3) the relation between unit force and fatigability, and 4) the extent to which reinnervated MUs recover their former properties. 2. MUs were isolated by ventral root dissection and stimulation in reinnervated and normal TA muscles, 3.5-8 mo after common peroneal (CP) nerve section and resuture and in age-matched control rats, respectively. The units were characterized physiologically for classification into four types: slow twitch (S), fast twitch, fatigue resistant (FR), fast twitch fatigue intermediate (FI), and fast twitch fatigue sensitive (FF). Four muscle fiber types were identified histochemically with the use of a modification of the techniques of Brooke and Kaiser, and Guth and Samaha to delineate fiber subtypes on the basis of the pH sensitivity of myofibrillar adenosine triphosphatase (ATPase). 3. Neither the time-to-peak twitch force development nor the profile of unfused tetanus ("sag test") was unambiguous in separating fast from slow MUs. However, all units with a time to peak greater than 22 ms were fatigue resistant, and this time was chosen to delineate fast from slow. The fast unit population was further subdivided on the basis of their fatigability. There is normally a small proportion of S units (6% S) that increased to 20% after reinnervation. Although the fast population was subdivided, there was a continuous distribution of fatigue indexes in normal and reinnervated muscles with the highest number of fast units falling into the FI category. The proportions of fast units were 28% FR, 45% FI, and 21% FF in normal muscles and 29% FR, 38% FI, and 13% FF in reinnervated muscles. 4. In normal muscles, delineation of fast and slow fibers and subdivision of fast fiber types on the basis of acid and alkali stability of myofibrillar ATPase provided a histochemical classification that showed 78% correspondence with physiological classification of the same identified units. In reinnervated muscles the correspondence between physiological and histochemical classifications was reduced to 72%. 5. The normal correlation between MU fatigability and isometric force in TA muscles was not seen in reinnervated muscles that contained more FR MUs. Mean fatigue index from normal units was significantly less at 0.55 +/- 0.03 (mean +/- SE) compared with 0.68 +/- 0.03 from reinnervated units.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597723 TI - Clinical experience with rhenium-186-labeled monoclonal antibodies for radioimmunotherapy: results of phase I trials. AB - Rhenium is a radionuclide with physical and chemical properties suitable for radioimmunotherapy. Two Phase I trials were carried out using 186Re-labeled murine monoclonal antibodies. Patients with refractory metastatic epithelial carcinoma received single doses of either 186Re-labeled intact NR-LU-10, a pancarcinoma antibody, 25-120 mCi/m2 (n = 15) or 186Re-labeled F(ab')2 fragment of NR-CO-02, an anti-CEA variant antibody, 25-200 mCi/m2 (n = 31). Prior to radioimmunotherapy, tumor localization of antibody was confirmed by 99mTc-labeled NR-LU-10 Fab or 99mTc-labeled NR-CO-02 F(ab')2 imaging. Dose-limiting myelosuppression was observed at 120 mCi/m2 following 186Re-NR-LU-10 intact antibody and at 150 mCi/m2 following NR-CO-02 F(ab')2 fragment in heavily pretreated patients. In patients with minimal prior therapy, a maximum tolerated dose for NR-CO-02 F(ab')2 was not reached by 200 mCi/m2. Non-marrow toxicity was minimal. Human anti-mouse antibody developed in all patients receiving intact NR LU-10, and in 86% patients receiving F(ab')2 NR-CO-02. One patient treated with 186Re NR-CO-02 achieved a partial response. We conclude that 186Re-labeled antibody can be safely administered with significant toxicity limited to marrow. PMID- 1597725 TI - Dosimetric evaluation of immunoscintigraphy using indium-111-labeled monoclonal antibody fragments in patients with ovarian cancer. AB - This study reports the biodistribution and dosimetry for a monoclonal antibody against ovarian carcinoma. Eight patients received 140 MBq 111In-OV-TL 3 F(ab')2; thereafter gamma camera imaging was performed daily up to 96 hr. By using the conjugated view counting method, activity in the organs was quantitated by phantom calibration and by whole-body measurements using a whole-body counter with the conjugated view counting method. Red bone marrow uptake was derived from regions of interest over the lumbar vertebrae and iliac crest. In both methods, organ uptake varied only slightly with time, having a mean value of approximately 18%, 4%, 6% and 17% of the injected dose in the liver, spleen, kidneys and red bone marrow, respectively. The mean radiation dose to these organs was 0.9, 1.5, 1.2 and 0.5 mGy/MBq. The effective dose equivalent was 0.4 mSv/MBq. In this study, two different methods of uptake calculations, result in similar values of organ uptake. PMID- 1597724 TI - Radioimmunotherapy of cancer: arming the missiles. PMID- 1597726 TI - A scintigraphic comparison of iodine-123-metaiodobenzylguanidine and an iodine labeled somatostatin analog (Tyr-3-octreotide) in metastatic carcinoid tumors. AB - A number of neoplasms are known to express somatostatin receptors, and the use of somatostatin receptor imaging in their localization has recently been described. We compared an 123I-labeled somatostatin analog Tyr-3-octreotide (TOCT) and 123I labeled metaiodobenzylguanidine (MIBG) scintigraphy in seven patients with histologically proven metastatic carcinoid tumors. The optimum time for identifying tumor uptake on scanning after [123I]MIBG was 24-48 hr, and after 123I-TOCT 10-30 min postinjection. Both radiopharmaceuticals showed a varying spectrum of tracer uptake ([123I]MIBG showed no uptake in one patient; minimal in two; moderate in two; and intense in two; 123I-TOCT showed no uptake in two patients; minimal uptake in one; moderate uptake in two; and intense uptake in two). In two patients, 123I-TOCT identified metastatic lesions not seen by [123I]MIBG scintigraphy. These preliminary results suggest that [123I]MIBG and 123I-TOCT are useful and complementary imaging techniques for detecting metastatic carcinoid tumors. PMID- 1597727 TI - PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma. AB - Pheochromocytomas are potentially curable causes of hypertension. These tumors are currently located by functional imaging with meta-iodobenzylguanidine (MIBG), usually labeled with 131I, or anatomic imaging (computed tomography, magnetic resonance). Hydroxyephedrine (HED) is a newly developed radiotracer that concentrates in adrenergic nerve terminals. When HED is labeled with 11C, its distribution can be mapped in vivo using PET. The purposes of this investigation were to characterize the uptake of 11C-HED in pheochromocytoma and to determine the feasibility and advantages of utilizing this compound as a tumor imaging agent. Ten patients with known or suspected pheochromocytoma were studied. Each patient underwent PET scanning with 11C-HED and conventional scintigraphy with MIBG. Pheochromocytomas were localized by PET scanning in 9 of the 10 patients. Image quality was excellent and superior to that obtained from planar and tomographic MIBG studies. The uptake of 11C-HED into pheochromocytomas was rapid; tumors were evident within 5 min following intravenous injection. All lesions within the field of view that were identified by MIBG scintigraphy were readily apparent. PET scanning with 11C-HED localizes pheochromocytoma using a specifically designed radiotracer and advanced imaging technology. The method has promise for locating the more elusive tumors. PMID- 1597729 TI - Precision of dual-energy x-ray absorptiometry in determining bone mineral density and content of various skeletal sites. AB - Repeated measurements of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) reliably indicate changes in the bone mineral content (BMC) of the lumbar spine and proximal femur, but its applicability to other sites has not been properly determined. The in-vivo day-to-day precision of DEXA (Norland XR-26) for lumbar spine, femoral neck, distal femur, patella, proximal tibia, calcaneus and distal radius was evaluated for 15 subjects who were scanned three times for 2 wk. Intra- and interobserver errors were also determined for image analysis. For clearly defined regions of interest, the following precision values were obtained for BMD with low intra- and interobserver error: 1.7% (lumbar spine), 1.3% (femoral neck), 1.2% (distal femur), 1.0% (patella), 0.7% (proximal tibia), 1.3% (calcaneus) and 1.9% (distal radius). The precision for BMC was lower. The results indicate that DEXA can successfully and precisely measure BMD of sites not commonly assessed by this technique. PMID- 1597728 TI - Radioiodine-131 therapy for well-differentiated thyroid cancer--a quantitative radiation dosimetric approach: outcome and validation in 85 patients. AB - For almost five decades, 131I treatment of thyroid cancer has been based empirically on administered activity rather than on actual radiation doses delivered. In 1983, we defined radiation dose thresholds for successful treatment. This report is concerned with the subsequent validation of those thresholds in 85 patients. The successful ablation of thyroid remnants occurred after a single initial 131I administration in 84% of inpatients and in 79% of outpatients when treatment was standardized to a radiation dose of at least 30,000 cGy (rad). Administered activities low enough to permit outpatient therapy could be used in 47% of the patients. Lymph node metastases were treated successfully in 74% of patients with a single administration of 131I calculated to deliver at least 8,500 cGy (rad). For athyrotic patients with nodal metastases only, success was achieved in 86% of patients at tumor doses of at least 14,000 cGy (rad). These success rates are equal to or better than those reported with empiric methods of 131I administration. The individualized treatment planning selectively allocates hospitalization and higher exposures to 131I to those patients who require them. PMID- 1597730 TI - Measurement of bone mineral content and bone density in healthy twelve-year-old white females. AB - Bone mineral content (BMC) and bone mineral density (BMD) measurements were made by dual-energy x-ray absorptiometry (DEXA) in 112 healthy 12-yr-old white girls for the purposes of: (1) establishing reference data on total-body mineral content of 12-yr-old girls and (2) comparing the lumbar spinal bone density values from a dedicated scan with the lumbar region of interest bone density values from a whole-body scan. Total BMC ranged from 799 g to 2083 g with mean and median values of 1276 g and 1218 g. Total-body bone density ranged from 0.75 to 1.03 g/cm2 with mean and median values of 0.88 and 0.87 g/cm2. The mean and median lumbar bone density values from the lumbar scan mode were 0.74 and 0.73 g/cm2 and were not significantly different from the mean and median lumbar bone density values of 0.71 and 0.70 g/cm2 obtained from the region of interest data from the total-body scan. These results establish baseline bone mass and bone density values for our longitudinal study of bone accretion in young women and validate the use of lumbar vertebral bone density values obtained from whole-body scans. PMID- 1597731 TI - Rapid radiotracer washout from the heart: effect on image quality in SPECT performed with a single-headed gamma camera system. AB - Technetium-99m-teboroxime demonstrates high extraction and rapid washout from the myocardium. To evaluate the feasibility of performing SPECT with this agent using a single-headed gamma camera system, a series of phantom studies were performed that simulated varying degrees of washout from normal and "ischemic" regions of the myocardium. In the absence of ischemic regions, short axis profiles were relatively unaffected by washout of less than 50% of activity over the duration of a SPECT acquisition. However, significant corruption of the SPECT data was observed when large (greater than a factor of 2) differences existed in the washout of activity from normal and "ischemic" myocardium. This corruption was observed with 30%-40% washout of activity from normal regions of the heart. Based on published washout rates, these results indicate that clinical studies with 99mTc-teboroxime may need to be completed within 2-4 min to order to prevent degradation of image quality due to differential washout effects. PMID- 1597732 TI - Gallium-labeled deferoxamine-galactosyl-neoglycoalbumin: a radiopharmaceutical for regional measurement of hepatic receptor biochemistry. AB - Galactosyl-neoglycoalbumin (NGA) is a synthetic ligand to the hepatocyte-specific receptor, hepatic binding protein. In-vitro and in-vivo characterization of a chelation-based derivative of NGA, deferoxamine-galactosyl-neoglycoalbumin (DF NGA), is described. A two-step glutaraldehyde method was used to covalently couple deferoxamine (DF) to NGA. Products with an average DF-to-NGA ratio of less than 2 contained less than 3% polymeric DF-NGA. All products retained the chelator after 12 mo of storage at 4 degrees C. Gallium labeling of DF-NGA-41 (41 galactose units per HSA) with an average of 1.1 DF per NGA was quantitative within 15 min after the addition of 67Ga-citrate. The labeled product was stable for at least 24 hr. Scatchard and reverse-binding assays of 67Ga-DF-NGA-41 revealed a forward binding rate constant kb similar to that of 125I-NGA-44. The %ID of 67Ga-DF-NGA-41 in rabbit liver was approximately 90% at 10 min after injection of 1.2 x 10(-9) mole DF-NGA per kilogram of body weight. This value decreased to 40% at a scaled molar dose of 1.2 x 10(-7) mol/kg. Biodistribution data of 67Ga-DF-NGA in rabbits was similar to 99mTc-NGA. High tissue specificity and facile labeling will make 68Ga-labeled neoglycoalbumin an ideal agent for regional measurements of receptor biochemistry in the investigational and clinical setting. PMID- 1597733 TI - Lymphocyte labeling with technetium-99m-HMPAO: a radiotoxicity study using the micronucleus assay. AB - The cytogenetic radiation damage to lymphocytes after in-vitro labeling of mixed leukocytes and isolated lymphocytes with 99mTc-hexamethylpropyleneamine oxime (HMPAO) was evaluated using the cytokinesis-blocked micronucleus assay. A direct assessment of the radiation damage to the lymphocytes after a labeling procedure of leukocytes separated from 46 ml blood with 740 MBq of 99mTc-HMPAO was not possible due to an almost complete impairment of the proliferative capacity. By starting with isolated lymphocytes, the number of micronuclei was studied versus the intracellular activity concentration in the range 0-3 MBq/10(7) lymphocytes for three donors. A comparison of these results with the dose response of the micronucleus incidence in lymphocytes after in-vitro irradiation with x-rays allowed an individual assessment of the x-ray dose, inducing the equivalent amount of clastogenic damage as the intracellular activity after 99mTc-HMPAO labeling. Based on an extrapolation of these data, the radiation damage of the lymphocytes due to self-irradiation in a labeling procedure of leukocytes with 740 MBq of 99mTc-HMPAO was estimated to be equivalent to 26 Gy of x-rays. Due to the observed almost complete inhibition of the proliferative capacity at this high dose level, the increased risk for a lymphoid malignancy after administration of isolated lymphocytes or mixed leukocytes labeled with 99mTc HMPAO activities sufficient for scintigraphy can be regarded as small. PMID- 1597734 TI - Diffuse pulmonary uptake of indium-111-labeled leukocytes in drug-induced pneumonitis. AB - Indium-111-labeled-leukocyte scintigraphy was performed on three febrile patients, two of whom had no signs or symptoms referable to the respiratory tract. The third patient had dyspnea on exertion, unchanged over two months. Their past histories were remarkable in that all three had recently undergone chemotherapy for malignancy (2 lymphoma, 1 malignant thymoma). Diffuse pulmonary uptake of labeled leukocytes was observed in all three individuals. As a direct result of leukocyte imaging, all three underwent fiberoptic bronchoscopy and transbronchial biopsy. The final diagnosis in each of these patients was drug induced pneumonitis, which responded to treatment with corticosteroids. This entity should be added to the group of conditions, both infectious and noninfectious, that cause diffuse pulmonary uptake on labeled leukocyte images. Moreover, in the appropriate clinical setting, even in the absence of pulmonary signs or symptoms, diffuse pulmonary uptake of labeled leukocytes should alert the physician to the possibility of drug-induced pneumonitis. PMID- 1597735 TI - Technetium-99m-labeled anti-fibrin monoclonal antibody accumulation in an inflammatory focus. PMID- 1597736 TI - Gallium-67 scintiscan in the diagnosis of primary splenic non-Hodgkin's lymphoma after the treatment of Hodgkin's disease. AB - A rare primary non-Hodgkin's lymphoma (diffuse large cell) of the spleen developed in a 72-yr-old man who had successful radiotherapy to the right inguinal region for Hodgkin's disease 23 yr ago. Radiologic findings, particularly the 67Ga scintigraphy finding, were very useful in leading to the correct diagnosis of malignant splenic lymphoma, in this case, preoperatively. PMID- 1597737 TI - Intrahepatic versus extrahepatic cholestasis in hepatobiliary scintigraphy. PMID- 1597738 TI - Whole-body positron emission tomography: Part I. Methods and performance characteristics. AB - Methods for whole-body PET imaging have been developed to provide a clinical tool for the detection and evaluation of primary and metastatic cancers. The axial FOV of the PET system is extended by imaging at multiple bed positions to cover the whole body. In typical rectilinear PET scans, only a small fraction of the data is collected to form two-dimensional projection images. In this work, 100% of the projection data was collected to form the two-dimensional projection images. These projection images were generated for continuous angles over 180 degrees by resorting sinogram data. In addition, tomographic images were formed by using filtered backprojection reconstruction without attenuation correction. Coronal and sagittal cuts were then extracted from the three-dimensional data set. The tomographic images were reconstructed to a resolution of 10.8 mm in all dimensions because of statistical limitations of the data. Both methods of image formation resulted in images of high quality with the tomographic reconstruction providing the highest contrast and resolution. An acquisition time of 1-2 min/bed position after a 10-mCi injection of [18F]fluoride ion or [18F]FDG was found to give a sufficient number of counts for producing images of good resolution and contrast, from a total scanning time of 32-64 min. PMID- 1597740 TI - SPECT of rapidly cleared tracers: imaging a Cheshire cat. PMID- 1597739 TI - A simulation of dynamic SPECT using radiopharmaceuticals with rapid clearance. AB - Data acquisition in SPECT assumes that there is no change in radionuclide distribution during data collection. However, this assumption is not valid in radiopharmaceuticals with rapid temporal changes in radioactivity. Artifacts and quantitative errors are studied using phantom studies, mathematical models, and clinical myocardial data. Projection data of each model were sequentially multiplied by weighting coefficients that varied mono-exponentially with time, and the SPECT images were reconstructed. A long data acquisition time in comparison to the clearance of the tracer can be a significant cause of artifact. When the myocardial septum-to-lateral count ratio is used as an index of distortion, a shorter acquisition time than the effective half-life of the tracer is required to reduce the error of the septum-to-lateral count ratio to within 10%. Since 180 degrees rotation acquisition causes artifacts depending on the direction of rotation, 360 degrees acquisition is preferable. Continuous repetitive rotation acquisition is a suitable method for dynamic SPECT to reduce quantitative errors and artifacts. PMID- 1597741 TI - Misalignment between PET transmission and emission scans: its effect on myocardial imaging. AB - Patient movement between PET scanning sequences can produce misalignment between attenuation and emission scans. Such misalignment introduces errors in the emission image. This study evaluates the severity of these errors and their effect upon quantitation of regional myocardial activity. Myocardial FDG scans from 14 patients were reconstructed with simulated translational, rotational and out-of-plane patient movement. Eight myocardial regions from each patient were examined to determine the effect such misalignment might have on regional myocardial activity. A 2-cm shift between attenuation and emission scans produced up to a 30% change in regional activity. Some regions of the myocardium increased while others decreased for a given magnitude and direction of shift, producing anomalous regional myocardial inhomogeneities in the image. Such changes could easily cause qualitative and quantitative misinterpretations. We present data permitting the reader to assess the magnitude of this effect in his/her own clinical setting. PMID- 1597742 TI - A noninvasive test of sphincter of Oddi dysfunction in postcholecystectomy patients: the scintigraphic score. AB - The ideal noninvasive test of sphincter of Oddi dysfunction (SOD) does not exist and the diagnosis of patients with postcholecystectomy pain often relies on invasive procedures. In this paper we describe a scintigraphic test for SOD: the scintigraphic score. This score combines quantitative and visual criteria for interpretation of hepatobiliary scans. Twenty-six consecutive postcholecystectomy patients underwent hepatobiliary imaging, ERCP, and sphincter manometry. Twelve patients had SOD and 14 had normal sphincters determined by clinical findings, ERCP, and manometric studies. All patients with normal sphincter had scores of 0 4, while patients with SOD had values of 5-12 for a perfect sensitivity and specificity of 100%. Hepatobiliary scans scored in this fashion may become the noninvasive test of choice to screen postcholecystectomy patients with suspected SOD. PMID- 1597743 TI - The scintigraphic evaluation of sphincter of Oddi dysfunction. PMID- 1597744 TI - Compensation for three-dimensional detector response, attenuation and scatter in SPECT grey matter imaging using an iterative reconstruction algorithm which incorporates a high-resolution anatomical image. AB - The use of SPECT to diagnose physiological alterations in disease states depends on the potential of SPECT to provide a quantitatively accurate reconstructed image. However, the reconstructed values depend upon the shape and size of the brain region as strongly as they depend upon true radioactivity concentration. We report here the results of applying an iterative reconstruction algorithm (IRA) to compensate for shape- and size-dependence, as well as for attenuation and scatter. The IRA is designed only for the reconstruction of images for which the true radioactivity in the white matter within the actual brain is negligible compared with the true radioactivity in the grey matter within the actual brain. The IRA incorporates an accurate three-dimensional model of detector response and utilizes an MRI image which defines the anatomical features of the brain being imaged by segmenting the grey, white and ventricular regions. It is the assumption of radioactivity localization exclusively in the grey matter which permits the efficient incorporation of the MRI image. The IRA was validated by simulation studies that utilized a slice through the basal ganglia in the realistic Hoffman three-dimensional mathematical brain model. FBP images deviate significantly from true radioactivity distribution, whereas IRA images are nearly identical to true radioactivity distribution, except for random fluctuations due to the presence of statistical noise. These results indicate that the application of the IRA will permit SPECT to distinguish deficits due to true physiological changes from apparent deficits due to imaging/reconstruction artifacts. PMID- 1597745 TI - Issues in the quantitation of reoriented cardiac PET images. AB - Reorientation of transaxial cardiac PET images into short-axis images has been shown by other investigators to improve visual identifiability of defects in myocardial tracer uptake. However, quantification of physiologic processes from such reoriented images may be complicated by errors introduced during the reorientation process. Therefore, a quantitative characterization of these errors is necessary. An annular phantom of human cardiac dimensions was imaged in a 15 plane positron emission tomograph at six angles (0 degrees, 5 degrees, 25 degrees, 45 degrees, 65 degrees, 85 degrees) and at two different axial sampling densities. In addition, two different reorientation interpolators were employed, one using three-dimensional linear interpolation and the other using a "hybrid" interpolation algorithm. Distortion of linear distances was variable but was minimized with denser axial sampling and the use of hybrid interpolation. Circumferential profile analysis, corrected for inhomogeneities in reoriented image spatial resolution, revealed a maximal loss of region of interest counts at 65 degrees of at least 14.4%. Reorientation errors were minimized by use of dense axial sampling, low angles of reorientation and use of the hybrid interpolation algorithm. PMID- 1597746 TI - A region of interest strategy for minimizing resolution distortions in quantitative myocardial PET studies. AB - The distortions inherent in PET images of the human heart due to finite image resolution and cardiac motion limit the capability to evaluate physiology quantitatively. A method based on a simple geometrical model of region of interest representations in physical space has been developed to minimize these distortions. In this paper, simulation studies have been performed to evaluate the noise characteristics of the method. This study demonstrates that unbiased estimates of kinetic model parameters which describe myocardial physiology can be measured with an accuracy of 7%-15% for scale-related parameters and 4%-16% for shape-related parameters of kinetic models in studies with the equivalent of 1 million events. Application of the techniques developed in this paper for the measurement of myocardial blood flow in eight dogs (14 independent flow states) shows a strong correlation with microsphere determined blood flow in the same animals (slope = 1.022, intercept = -0.18, r = 0.96). PMID- 1597747 TI - Effect of differential tracer washout during SPECT acquisition. PMID- 1597748 TI - Decision analysis after an indeterminate probability lung scan. PMID- 1597749 TI - Fast diagnosis of abdominal infections with technetium-99m-HMPAO-leukocytes. PMID- 1597750 TI - Questions about the future of DOE isotope production and research. PMID- 1597751 TI - Mallinckrodt Fellow probing immune mechanisms in heart disease. PMID- 1597752 TI - Functional brain scans as evidence in criminal court: an argument for caution. PMID- 1597753 TI - Who's to shoulder the burden of low-level radioactive waste? PMID- 1597754 TI - Envisioning the future: challenges in community health nursing. PMID- 1597755 TI - Ten steps for managing organizational change. AB - Managing interdepartmental relations in healthcare organizations is a major challenge for nursing administrators. The authors describe the implementation process of an organization-wide change effort involving individuals from departments throughout the medical center. These strategies can serve as a model to guide effective planning in other institutions embarking on change projects, resulting in smoother and more effective implementation of interdepartmental change. PMID- 1597756 TI - Implementing an integrated financial system. AB - Faced with four redundant date entry software systems and a staff that relied heavily on manual systems, agency administrators searched for a fully integrated automation system. The author describes the agency's success with and staff's acceptance of the chosen system. PMID- 1597757 TI - Exempt salary administration. Redesigning staff nurse compensation. AB - An exempt salary administration program can provide positive benefits for the professional nurses and the hospital, thus creating a "win-win" strategy for today's competitive environment. This compensation change requires careful planning and open discussion between hospital administration and professional nursing staff. In this era of diminishing human and economic resources, selection of nurse compensation programs that mirror the culture and strategic goals of an organization is key to the success of the institution. PMID- 1597759 TI - Insurance for HIV exposure. PMID- 1597758 TI - Strengthening hospital nursing, Part 2. Characteristics of effective planning processes. AB - Characteristics of the planning process for 213 hospitals participating in Phase 1 of the Strengthening Hospital Nursing Program (SHNP) are described. Differences in planning between the Phase 2 implementation sites and those sites not selected for continued funding are explored. Factors associated with positive planning outcomes among participating hospitals are delineated. The use of the SHNP planning process as a model for other hospitals is suggested. This article is Part 2 of a 3-part series on the planning process within the national Strengthening Hospital Nursing Program. Part 1, contrasting single and networked hospitals, appeared in the May issue of JONA. Part 3, which examines interdisciplinary differences, will appear in the July/August issue. PMID- 1597760 TI - The role of the Medicare fiscal intermediary and the Regional Home Health Intermediary, Part 1. AB - The Medicare fiscal intermediaries (FIs) are private insurance companies that serve as the federal government's agents in the administration of the Medicare program, including the payment of claims. There are two primary functions for the FI--reimbursement review and medical coverage review. Hospital-based home health agencies relate to the hospital's FI for reimbursement purposes. All home health agencies are assigned to a special FI, the Regional Home Health Intermediary (RHHI), for medical review issues. The same or a different FI may audit the hospital's cost report. Freestanding home health agencies deal with separate reimbursement and medical review divisions within a single RHHI's office. The author reviews the role of the Medicare FI and the RHHI and their relationship to home health agencies. Part 2 will appear in the July/August issue. PMID- 1597761 TI - Coaching. Developing key players. AB - Coaching provides nurse administrators with a framework for developing their management team. Middle managers who have been coached can use coaching to provide performance feedback and encourage teamwork within their staff. Coaching as a management strategy should be valued and practiced from the nurse executive on down through the organization. PMID- 1597762 TI - Self-management for nurses. AB - Nurses at a 119-bed hospital in the southwestern United States successfully managed themselves for 5 years without head nurses. The authors describe the context for self-management, the initiation of the self-managed model, and the role and tasks of the self-managed nurse. A summary of self-management training and an operational retrospective summary of the program are given. PMID- 1597763 TI - Creating new practice models and designing new roles. Reflections and recommendations. PMID- 1597764 TI - Return to work policies. PMID- 1597765 TI - Arm pain in the workplace. A small area analysis. AB - In the mid-1980s, use-related arm pain was recognized as a major issue for worker health and workplace safety. National policy targeted these "cumulative trauma disorders," "overuse syndromes," and "motion illnesses" for a "special emphasis program" by the Occupational Safety and Health Administration, a federal regulatory agency. The program begins with case recognition to identify the responsible ergonomic hazards with the goal of mandating ergonomic remedies. This report is a small area analysis of the impact of this process on the US West Communications, Inc work force. US West employs some 55,000 workers in 14 states. Commencing in the mid-1980s, workers in four of these states complained of upper extremity pain and were diagnosed as suffering from conditions encompassed by the "cumulative trauma disorders" rubric. The incidence was tenfold higher in one task category, directory assistance operators. No ergonomic descriptor can account for the four endemics of arm pain in directory assistance operators. The response of the medical communities to the plight of these injured claimants varied considerably from community to community. Denver represents one extreme where the clinical judgments led to multiple surgical interventions, generated a total direct cost of some $1.5 million, and left many permanently disabled workers in their wake. This analysis raises many reservations about the validity of the "cumulative trauma disorder" hypothesis and provides an object lesson in the potential for untoward outcomes from the premature introduction of clinical hypotheses into the arena of health policy. PMID- 1597766 TI - Assessing occupational disability from asthma. AB - Asthma is receiving increased attention as a cause of occupational disability, both by virtue of occupational causation and by interactions between work and pre existing asthma. Reasons for the failure of pneumoconiosis-related disability evaluation systems to be applicable to asthma are discussed, including the inherent variability of asthma, its responsiveness to treatment, and its variable time course with respect to occupational exacerbation. A distinction is made between the trait of airway hyperresponsiveness and the disease of asthma. A scheme for organizing reports about asthma-related disability clearly specifies the questions that need to be addressed. PMID- 1597767 TI - Work-related toxic epidermal necrolysis? AB - A case of toxic epidermal necrolysis is described in an employee of a company that carries out plastic extrusion using various resins, including cellulose acetate, co-polyester, polyvinyl chloride, acrylonitrile-butadienestyrene, and polyethylene. Air sampling during normal operating conditions indicated only trace amounts of hydrogen chloride and the plasticizer diethylphthalate. However, pyrolysis products of resin plugs could include compounds such as formaldehyde, acrylonitrile, and chlorinated hydrocarbons that have been associated with previous case reports of either erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis. The development of toxic epidermal necrolysis in this worker was directly preceded by exposure to a vapor from a machine used to dry cellulose acetate. The problems in determining work relatedness and advising about return to work are discussed. PMID- 1597768 TI - Research and clinical criteria for development of neurobehavioral test batteries. AB - Because neuropsychological testing can detect subtle changes in central nervous system function resulting from occupational and environmental exposure to toxic chemicals, it has been widely used in behavioral neurotoxicologic investigations. However, work in this field often has ignored the distinction between clinical and research testing when applying these assessment techniques. Experimental studies generally compare groups of subjects on specific outcome measures, whereas clinical work usually is focused on diagnosis and treatment of individual patients. Therefore, the inclusion criteria applicable to the selection of neuropsychological test batteries are different in research and clinical settings. Issues germane to test selection in research settings include sensitivity to neurotoxins, psychometric standards, sensitivity to central nervous system dysfunction, overview of cognitive functions, sampling of cognitive processing, sampling of output modalities, and examination of theoretical constructs. The usual questions asked in the clinical setting can be addressed most efficiently when the following issues are considered in test selection: sensitivity to specific toxicant exposure, estimation of native ability patterns, differential diagnosis, developmental specificity of tests and exposure effects, and description of patterns of cognitive strengths and weaknesses. PMID- 1597769 TI - Antineoplastic drug handling protection after OSHA guidelines. Comparison by profession, handling activity, and work site. AB - Although Occupational Safety and Health Administration (OSHA) issued antineoplastic drug handling guidelines in 1986, literature reports indicated that use of protection in the early 1980s did not meet OSHA standards. This study investigated the use of protection by pharmacy and nursing staff in a national sample of facilities participating in the National Surgical Adjuvant Breast and Bowel Project collaborative clinical trials network of the National Cancer Institute. Extent of handling, handling activity, and use of protection are compared by work setting and profession. Use of protection by the study sample in 1988 to 1989 is compared with their past use, with use of protection in previous studies, and with OSHA guidelines. In general, pharmacists are better protected than are nurses, and hospital staff are better protected than staff in outpatient settings who also tend to handle more drugs. Although improving over time, protective garment use does not meet OSHA guidelines, particularly among nurses when administering agents or handling patient excreta. PMID- 1597770 TI - A program model to enhance adherence in work-site-based fitness programs. AB - We describe a program model designed to achieve high adherence, a major problem for work-site exercise/fitness programs. Our model is a 6-month program consisting of 15 1-hour program meetings, with participants exercising on their own time four times per week. Procedures employed to enhance adherence are contracting, group competition, monitoring, and social support. This program model has been applied nine times. One hundred fifty-nine university employees took part in the initial test with a dropout rate of 9% (15 persons). The average adherence rate for nondropouts was 98%, which is higher than rates usually reported in the literature. Adherence was defined as exercising four times a week. PMID- 1597771 TI - What is a program: thoughts on definitions in work-site health promotion. PMID- 1597772 TI - Epidemiologic study of lung cancer mortality in workers exposed to titanium tetrachloride. AB - A study was done to examine whether workers exposed to titanium tetrachloride had significantly higher risks of lung cancer, chronic respiratory disease, pleural thickening/plaques, or pulmonary fibrosis than referent groups. A total of 2477 employees from two titanium dioxide plants were studied. Of that group, 969 employees exposed to titanium tetrachloride were observed from 1956 through 1985 for cancer and chronic respiratory disease incidence and from 1935 through 1983 for mortality. A cross-sectional sample of 398 employees was evaluated for chest roentgenogram abnormalities. Cohort analyses showed that the risk of developing lung cancer and other fatal respiratory diseases was not statistically significantly higher for the titanium tetrachloride-exposed workers than for the referent group. Nested case-control analyses found no statistically significant association between titanium tetrachloride exposure and risk of lung cancer, chronic respiratory disease, and chest roentgenogram abnormalities. No cases of pulmonary fibrosis were observed among titanium tetrachloride-exposed employees. Smoking was found to be a strong predictor of lung cancer mortality in the nonexposed employees with an increased risk of dying from lung cancer up to 7 fold higher in current smokers than in nonsmokers. PMID- 1597773 TI - A survey of the prevalence of epididymitis in an industrial setting. AB - In response to concerns about the occurrence of epididymitis among employees at a Du Pont textile fibers plant, information was obtained from 1342 (94.8%) active male employees on history of epididymitis and/or orchitis (6.8%), prostatitis (11.5%), other genitourinary conditions, and vasectomy. Vasectomy was associated with an odds ratio of 3.26 (90% confidence interval (CI) = 1.96, 5.43) for subsequent development of epididymitis. History of prostatitis was also a risk factor for epididymitis (odds ratio = 5.02, 90% CI = 2.94, 8.58). PMID- 1597774 TI - Quality of death certificate occupation data for a cohort of aluminum industry workers. AB - Occupational data from death certificates have been used extensively in health studies but their quality has been questioned. In this study, data from the death certificates of aluminum plant workers were analyzed. Aluminum industry employment was indicated in the certificate occupation/industry statement of 321 (80%) of the 403 total workers, 263 (94%) of the 280 workers who had been employed for 10 years or more, 156 (94%) of the 166 workers who died while employed, and 131 (95%) of the 138 workers who died after retirement. Of 82 certificates that did not indicate aluminum industry employment, 57 (70%) were from workers who were employed for fewer than 10 years and terminated employment for reasons other than death or retirement. This study supports the usefulness of death certificate occupational information. PMID- 1597775 TI - Employee assistance programs. PMID- 1597776 TI - Improving physical fitness and reducing injuries in physically demanding jobs. PMID- 1597777 TI - Effects of cholinergic agents on the metabolism of choline in muscle from Ascaris suum. AB - The incorporation of [methyl-14C]choline into the choline-containing compounds of Ascaris suum muscle and the effects of acetylcholine and its agonists, carbachol and levamisole, on this incorporation were studied. Previous experiments reported a stimulation of phosphatidylcholine (lecithin) metabolism upon the administration of acetylcholine. Acetylcholine administered in vitro to A. suum muscle and body wall preparations resulted in a stimulation of phospholipase C activity that, in turn, produced an increased rate of hydrolysis of phosphatidylcholine to the corresponding diacylglyceride (DAG). The DAG, in turn, may act as a second messenger as it is required for the activation of an A. suum protein kinase C. Evidence presented here is in accordance with this hypothesis. The administration of cholinergics resulted in a stimulation of phosphatidylcholine turnover. Acetylcholine also stimulated isotope incorporation into glycerophosphorylcholine, presumably as a consequence of enhanced phospholipid turnover. These events appear to be associated with the ligand binding to the acetylcholine receptors of the A. suum muscle. Choline kinase activity is suggested in order to maintain the observed high ratio of phosphorylcholine to choline. Findings indicate that in the parasite's muscle phosphatidylcholine metabolism may be linked to receptor-dependent responses and subsequent signal transduction. PMID- 1597778 TI - Cestode parasites in Potamotrygon motoro (Natterer) (Chondrichthyes: Potamotrygonidae) from southwestern Brazil, including Rhinebothroides mclennanae n. sp. (Tetraphyllidea: Phyllobothriidae), and a revised host-parasite checklist for helminths inhabiting neotropical freshwater stingrays. AB - Specimens of 5 species of cestodes were collected in 6 specimens of the freshwater stingray species Potamotrygon motoro (Natterer), collected in the vicinity of Corumba, Mato Grosso do Sul, Brazil. Acanthobothrium regoi, Potamotrygonocestus orinocoensis, Rhinebothroides venezuelensis, and Rhinebothrium paratrygoni are reported from P. motoro and from southwestern Brazil for the first time. Rhinebothroides mclennanae n. sp. appears to be the sister species of Rhinebothroides glandularis, the only other member of the genus exhibiting darkly staining glandular cells lying free in the parenchyma surrounding the terminal genitalia. The new species resembles Rhinebothroides glandularis, Rhinebothroides freitasi, and Rhinebothroides scorzai by having poral ovarian arms that extend anteriorly beyond the posterior margin of the cirrus sac, coiled vaginae, and vitelline follicles not interrupted on the poral side in the vicinity of the genital pore. It differs from all 6 previously described members of the genus by possessing an average of 31 testes per proglottid, compared with an average of 45 for R. glandularis, 55 for R. freitasi and R. venezuelensis, 77 for Rhinebothroides circularisi and Rhinebothroides moralarai, and 80 for R. scorzai. An updated phylogenetic tree for Rhinebothroides is presented. PMID- 1597780 TI - Interbreeding in the subfamily Ostertagiinae (Nematoda: Trichostrongylidae) of ruminants. AB - The interbreeding of 6 species of ostertagiines was studied in a sheep model. Virgin young females of selected nonpolymorphic strains of Ostertagia ostertagi, Ostertagia leptospicularis, and Teladorsagia circumcincta were mated with various male ostertagiines. Interbreeding was successful between O. ostertagi and Ostertagia lyrata, O. leptospicularis and Ostertagia kolchida, and T. circumcincta and Teladorsagia trifurcata, respectively. Their offspring were fertile and resembled one parent or the other without intermediate forms: each pair is a polymorphic species. Infertile hybrids, intermediate in form, were obtained from interbreeding between O. ostertagi and O. leptospicularis and they remain valid species. PMID- 1597779 TI - Neobenedenia pargueraensis n. sp. (Monogenea: Capsalidae) from the red hind, Epinephelus guttatus, and comments about Neobenedenia melleni. AB - Neobenedenia pargueraensis n. sp. from Epinephelus guttatus of Puerto Rico differs from all known species in possessing scoop-shaped accessory sclerites with pointed tips. It is most similar to Neobenedenia melleni and Neobenedenia longiprostata but differs from the former in having a fenestrate ovary and from the latter in that the ducts of the accessory glands are short, terminating just anterior to the vitelline reservoir rather than reaching the caudal end of the body. It differs from both species in having smooth rather than lobate testes. Neobenedenia melleni occurs throughout the tropical and subtropical western North Atlantic including Bermuda. It kills aquarium and aquaculture fishes with massive infestations and is a severe restraint on the culture of tilapia in sea water in the Caribbean. PMID- 1597781 TI - Cross-transmission studies with Eimeria arizonensis-like oocysts (Apicomplexa) in New World rodents of the Genera baiomys, Neotoma, Onychomys, Peromyscus, and Reithrodontomys (Muridae). AB - Cross-transmission experiments were performed using oocysts of an Eimeria arizonensis-like coccidian from Peromyscus leucopus and Peromyscus truei, an E. arizonensis-like coccidian from Reithrodontomys fulvescens, Eimeria baiomysis and Eimeria taylori from Baiomys taylori, Eimeria albigulae from Neotoma albigula, and Eimeria onychomysis from Onychomys spp., between representatives of the above host genera. The E. arizonensis-like coccidian from R. fulvescens infected Reithrodontomys megalotis, Reithrodontomys montanus, and Peromyscus leucopus. Oocysts of E. arizonensis from P. leucopus could be transmitted to both P. leucopus and R. megalotus. Oocysts of E. baiomysis and E. taylori infected only B. taylori. Oocysts of E. arizonensis from P. truei infected P. truei but not Neotoma mexicana or Onychomys leucogaster. Oocysts of E. albigulae from N. albigula were infective for N. mexicana but not for P. truei or O. leucogaster. Oocysts of E. onychomysis from Onychomys spp. infected O. leucogaster but not N. mexicana or P. truei. These results demonstrate that Peromyscus and Reithrodontomys, genera known to be related very closely evolutionarily, are capable of sharing E. arizonensis, whereas morphologically similar coccidians (E. albigulae, E. baiomysis, and E. onychomysis) from more distantly related hosts, are probably distinct and more stenoxenous. This also is the first report of coccidians infecting species of Reithrodontomys. PMID- 1597782 TI - DL-alpha-difluoromethylarginine inhibits intracellular Trypanosoma cruzi multiplication by affecting cell division but not trypomastigote-amastigote transformation. AB - DL-alpha-difluoromethylarginine (DFMA), a specific, irreversible inhibitor of arginine decarboxylase (ADC), decreases the capacity of Trypanosoma cruzi to invade and multiply within different types of mammalian host cells in vitro. In this work we found that inhibition of intracellular growth results from selective impairment of amastigote division without appreciable alteration of the capacity of the invading trypomastigotes to transform into the replicative amastigote form. Addition of agmatine, the product of arginine decarboxylation, reversed the inhibitory effect of DFMA. Inhibition of ornithine decarboxylase activity by DL alpha-difluoromethylornithine present in the medium prior to and during infection did not affect trypomastigote transformation or amastigote replication and did not change the magnitude of the inhibitory effect of DFMA on parasite multiplication. Hence, neither polyamine synthesis via the ornithine decarboxylase pathway nor salvage of host cell polyamines by T. cruzi appeared to be a likely explanation for the normal rate of parasite transformation that was seen in the presence of DFMA. Two clones of T. cruzi, TMSU-1 and TMSU-2, were tested for their degrees of sensitivity to the inhibitory effects of DFMA. Both trypomastigote association with (i.e., binding to and penetration of) myoblasts, and intracellular amastigote multiplication by either clone were found to be significantly (P less than 0.05) but not completely inhibited by DFMA. Therefore, the partial inhibition of T. cruzi infectivity and replication caused by DFMA is unlikely to represent a composite of effects of the drug on DFMA-sensitive and insensitive clones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597783 TI - Transmission pattern and intraspecific competition as determinants of population structure in pinworms (Oxyurida: Nematoda). AB - The transmission pattern of Zonothrix columbianus (Nematoda: Oxyurida) in its host Tropisternus columbianus (Coleoptera: Hydrophilidae), an aquatic beetle, was studied to determine whether parasites were dispersed with their hosts and to examine the possible role of intraspecific competition in limiting population size. Beetles were sampled at regular intervals from fall 1986 through fall 1989 and examined for worms. Worms, absent in larval stages of the host, were uncommon in newly metamorphosed beetles and therefore probably do not infect adult stages until after they have dispersed; worms are not dispersed with the host. Prevalence reached its lowest points in spring and fall when newly metamorphosed beetles were most common, but it was near 100% for most of the year. Worms were uniformly distributed in the host population. Many hosts had exactly 1 male and 1 female worm; the high prevalence suggests that this infrahost population results from interference competition between males on the one hand and females on the other. Only 3 of 285 beetles contained more than 1 male. Females shared the host with members of the same sex more commonly than males, but females from hosts harboring more than 1 female had significantly fewer eggs than lone females in hosts. Numbers of adult stages of beetles were estimated during spring, summer, and fall of 1989 and were lower in early spring and late fall. Because worms do not disperse with hosts, the panmictic unit could be estimated from the number of infected beetles; this probably was about 50 individuals during the winter bottleneck. PMID- 1597784 TI - Settling rates and density of spores of Henneguya doori (Myxosporea) in water. AB - Using Henneguya doori from Perca flavescens (yellow perch), the current study provides a method for examining settling rates, attitudes, and densities of myxosporean spores. Fresh and fixed spores settled similarly at 8.34 x 10(-6) m/sec and 8.53 x 10(-6) m/sec, respectively. The spores settled in the anterior end first, did not rotate, and had a specific gravity of 1.062. Comparison of settling rates proved more effective for determining spore density than direct chemical estimation. The slow rate of settling permits effective dispersal in open water. PMID- 1597785 TI - The role of the mosquito peritrophic membrane in bloodmeal digestion and infectivity of Plasmodium species. AB - Secretion and luminal formation of the peritrophic membrane (PM) were induced in female Anopheles stephensi and Aedes aegypti by feeding the mosquitoes on a warmed suspension of latex particles in Ringer's solution. The PM in A. stephensi was produced from apical secretion vesicles stored in the midgut epithelial cells and secreted into the lumen during feeding. In A. aegypti, the PM was formed de novo. When the latex feeding was followed 24 hr later by a meal of lyophilized pig blood, the 2 mosquito species exhibited very different modifications to their PM structure; in A. stephensi no PM was formed around the blood meal, whereas de novo synthesis of the PM in A. aegypti continued during the blood meal, with the resulting PM greatly thickened compared to the normal feeding. This artificial induction of PM formation was used as the basis to study the role of the PM in blood meal digestion and in infectivity of mosquitoes by the appropriate species of Plasmodium. The feeding of a latex suspension alone had no stimulatory effect on the 2 major midgut proteases, trypsin and aminopeptidase, in either species. After a blood meal alone, proteases rose to maximum activity at 30 hr and 24 hr after feeding in A. stephensi and A. aegypti, respectively. After double feeding, protease activities in both species were almost identical to those in blood-fed mosquitoes. Neither the absence of a PM (in A. stephensi) nor the presence of a thickened PM (in A. aegypti), therefore, has any effect on the ability of mosquitoes to digest a blood meal. Malaria infectivity, measured by oocyst counts, also was compared after normal and double feeding using infective blood meals. Infectivity of A. stephensi by Plasmodium berghei was unaffected by the presence or absence of the PM. The thickened PM produced by double feeding in A. aegypti caused a reduction of midgut infectivity by Plasmodium gallinaceum. These results suggest that the PM may act as a partial, but not an absolute, barrier to invasion of the midgut by the ookinete. PMID- 1597786 TI - Schistosoma mansoni infections in neonatal Biomphalaria glabrata snails. AB - In areas endemic for schistosomiasis, the population dynamics of the snail intermediate hosts have a direct effect on parasite transmission. The present study focused on the potential for neonatal Biomphalaria glabrata snails to become infected with Schistosoma mansoni and to produce cercariae under various conditions. It was found that snails as small as 0.74 mm in shell diameter could survive miracidial penetration and could release cercariae when as small as 1.6 mm in diameter. Cercariae produced by small snails were equally infectious for mice when compared with those shed by larger snails. Likewise, histological examination of neonatally exposed snails revealed normally developing parasites at all stages of infection. It was found that in 2 snail populations expressing either high or low susceptibility to the parasite, peak susceptibility occurred at 25 days of age in both groups. Daily cercarial production for neonatally exposed snails was initially low but increased dramatically as the snails grew, eventually reaching values as high as 2,100 cercariae/snail/day. A moderate to high percentage of snails infected as neonates was eventually capable of simultaneously producing both eggs and cercariae. These studies emphasize the potential importance of neonatal and preadult snails in helping to maintain foci of S. mansoni infection in endemic areas. PMID- 1597787 TI - Identification of surrogate rodent hosts for larval Onchocerca lienalis and induction of protective immunity in a model system. AB - The objectives of this project were to screen a variety of inbred rodent species and strains to determine their usefulness as surrogate hosts for the study of the early larval development of Onchocerca lienalis and then to use a selected model to study the induction of protective immunity. In the primary screen, 6 strains of mice, 5 strains of rats, jirds, and multimammate rats were tested. Animals were infected with fresh O. lienalis by subcutaneous implantation of third-stage larvae (L3) contained in diffusion chambers covered with 5.0-microns pore-size membranes. After 7 days the chambers were recovered, and larval viability and growth were assessed. Approximately one-half of inoculated larvae were recovered alive regardless of the host tested. Larvae were implanted in CBA/J and DBA/2J mice in chambers covered with membranes that prevented host cells from entering; survival and growth rates of the larvae were not altered by the absence of cells from the chambers. Cryopreserved larvae were implanted in chambers with 5.0 microns pore-size membranes in CBA/J and DBA/2J mice and Wistar Furth rats for 3 28 days. No statistically significant difference was seen in the larval recoveries on days 3-28 in all 3 hosts. Statistically significant increases in length were seen in the 3 strains from day 3 to day 14, after which growth appeared to cease. Molting from L3 to fourth-stage larvae was observed in all 3 hosts beginning on day 3, with most larvae completing the molt by day 7.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597788 TI - Schistosoma japonicum: immunoinhibitory studies on hemoglobin digestion using heterologous antiserum to bovine cathepsin D. AB - Antibody against purified bovine cathepsin D was raised in rabbits, and the polyclonal antiserum was tested to determine its ability to inhibit the hemoglobinolytic activity of the crude enzyme preparation (CEP) from adult Schistosoma japonicum and its effect upon in vitro cultured Schistosoma mansoni schistosomules. The 100,000 g supernatant fraction (CEP) from lyophilized adult worms was preincubated with antiserum and subsequently incubated with hemoglobin. Hemoglobinolytic activity was determined by sodium dodecyl sulfate-polyacrylamide gel electrophoretic procedures. Five hours of incubation failed to diminish hemoglobin concentration in experimentals, whereas controls treated with preimmune serum displayed hemoglobin degradation. Pepstatin inhibited hemoglobin degradation. Western blot analysis of the CEP revealed a broad band of activity at approximately 45 kDa. Schistosomules incubated in vitro either in the antiserum or pepstatin and subsequently exposed to host erythrocytes showed a marked inhibition of digestive activities. Although structural changes were not evident in the gastrodermis, some perturbation of the tegument was observed. Schistosomules fed host erythrocytes and postincubated in the antiserum displayed increased tegumental perturbation and extensive alteration of the gastrodermis, including dilation of cisternae and membrane disruption. Schistosomules exposed to preimmune serum were normal in all respects. PMID- 1597789 TI - Localization of a low molecular weight antigen of Eimeria tenella by use of hybridoma antibodies. AB - Three monoclonal antibodies (Mabs), found by western blot analysis to recognize 10-kDa bands of Eimeria tenella sporozoite preparations, were used with immunoelectron (IE) microscopy, immunogold-silver staining (IGSS), and indirect immunofluorescent antibody (IFA) light microscopy to determine the location and distribution of the antigens in or on extra- and intracellular parasites. All 3 of the Mabs (designated C3, E5, and 1231) were found by IE microscopy to label amylopectin granules of extracellular sporozoites. Additionally, these Mabs extensively gold-labeled the sporocyst wall. In cultured primary chicken kidney cells inoculated with sporozoites of E. tenella, IGSS showed surface labeling of the parasite and intense labeling of the infected host cells by 6 hr postinoculation (PI). At 24 hr PI, host cell vacuoles in infected and uninfected cells were labeled by the 3 Mabs by IFA. The E5 and C3 Mabs also were seen to label the host cell membrane of newly infected cells. The C3 and 1231 Mabs showed little label of the host cells by 48 hr PI, but the parasites still were labeled up to 96 hr PI. The E5 Mab had intense IFA labeling of infected host cells at 48 hr PI. The results of this study indicate that parasites apparently release antigenic material during the early stages of parasite development and that this material is found internally and/or on the surface of the infected host cells. PMID- 1597790 TI - Augmentation of host's naturally acquired immunity by solubilized membrane-bound midgut proteins of the tick Rhipicephalus appendiculatus. AB - Immune resistance of rabbits to the hard tick Rhipicephalus appendiculatus induced by combined tick infestations and immunization with solubilized midgut membrane proteins were compared with resistance due to 1-3 infestations or immunization alone. Results demonstrate that the level of exposure of rabbits to ticks used in the study does not significantly affect the immune expression resulting from immunization and that the latter augments the resistance due to infestation. PMID- 1597791 TI - Immunological mediation of gonadal effects on experimental murine cysticercosis caused by Taenia crassiceps metacestodes. AB - Female BALB/c mice are naturally more susceptible than males to intraperitoneal experimental infection with Taenia crassiceps metacestodes. Gonadectomy tends to equalize susceptibility between sexes by reducing in half the mean individual intensity of females and by tripling that of males. The effect of gonadectomy is seen only in mice with intact immune systems but not in irradiated mice. Purified sex hormones (17-beta estradiol, testosterone, and progesterone) do not affect cysticercus reproduction or growth in vitro. Thus, gonadal effect on mouse susceptibility to cysticercosis appears to be mediated via the immune system, and it is probably not the consequence of the major sex steroids acting directly upon the parasites. Because sublethal irradiation increases the intensity in gonadectomized females and intact males, whereas that of gonadectomized males and intact females remains unchanged, irradiation results are consistent with the hypothesis that immunological events that participate in controlling the growth of cysticerci are inhibited by ovaries and stimulated by testes. PMID- 1597792 TI - Role of the eosinophil in serum-mediated adherence of equine leukocytes to infective larvae of Strongylus vulgaris. AB - The adherence of equine leukocytes to Strongylus vulgaris infective larvae (L3) in the presence of normal and immune sera was examined in vitro. Immune sera promoted adherence of buffy coat cells from ponies with S. vulgaris-induced eosinophilia (eosinophilic ponies) to S. vulgaris L3. However, eosinophils in the buffy coat cells were the predominant adherent cell type. Studies using leukocyte populations enriched for eosinophils, neutrophils, and mononuclear cells from eosinophilic ponies support the observations using buffy coat cells that eosinophils were the main effector cells. Adherent eosinophils from eosinophilic ponies immobilized L3. Neutrophils were less adherent and did not immobilize L3. Mononuclear cells failed to adhere. Normal eosinophils from strongly-naive ponies did not immobilize S. vulgaris L3 in the presence of immune serum, suggesting the in vivo activation of eosinophils in eosinophilic animals. Immune serum promoted less adherence of buffy coat cells to Strongylus edentatus or mixed species of Cyathostominae L3, suggesting that the serum-mediated cellular adherence phenomenon was species-specific. Normal serum promoted less cellular adherence to S. vulgaris L3 than immune serum. The adherence mediated by normal serum was removed by heat inactivation, suggesting that this nonspecific phenomenon was a complement-mediated reaction. Immune globulins promoted reactions similar to that seen using heat-inactivated immune serum, whereas normal globulins did not promote adherence. Immune globulins absorbed with pieces of S. vulgaris adult worms did not promote the adherence of buffy coat cells to S. vulgaris L3, suggesting that adult and L3 stages share antigens important in this phenomenon that resulted in the removal of specific adherence antibody during absorption. PMID- 1597793 TI - Development of a polymorphic strain of Plasmodium vivax in monkeys. AB - A strain of Plasmodium vivax from Thailand with a polymorphic repeat unit of the circumsporozoite protein was established in Saimiri sciureus boliviensis and 3 species of Aotus monkeys. All 11 attempts to transmit infection via sporozoite inoculation, 4 times to splenectomized S. sciureus boliviensis, 2 times to splenectomized Aotus nancymai, and 5 times to intact Saimiri monkeys, were successful. Anopheles freeborni, Anopheles stephensi, Anopheles dirus, and Anopheles gambiae mosquitoes were infected by feeding on parasitemic blood from a chimpanzee and an Aotus azarae boliviensis monkey. Our results indicate that this strain may be useful in antisporozoite vaccine trials. PMID- 1597794 TI - Growth and development of Haemonchus contortus in jirds, Meriones unguiculatus. AB - Growth and development of Haemonchus contortus were examined in jirds and were compared to these processes in lambs. Number, sex, size, and stage of development were determined for worms recovered at necropsy at various times postinoculation (PI) from immunosuppressed jirds inoculated with approximately 1,000 exsheathed infective larvae (L3) of H. contortus. In addition, gastric tissue samples from jirds were examined histologically. Parallel studies were done in lambs inoculated with approximately 7,500 L3. Typically, 5-30% of the inoculum established and survived in jirds at reasonably stable numbers to day 14 PI. By day 21 PI, worm numbers in jirds decreased dramatically. Although the parasite was similar in size and development on day 4 PI in jirds and lambs, from day 7 PI on, worms were significantly smaller and less developed in jirds. On histological examination, the parasite was found only in the glandular portion of the stomach of jirds (anatomically similar to its predilection site in the abomasum of lambs), and histological changes were consistent for both host species. Although growth and development of H. contortus are slower and incomplete in jirds, the parasite establishes, grows, and develops (at anatomically comparable sites in both hosts) in this model. Thus, the model appears to provide a useful laboratory host to study H. contortus. PMID- 1597795 TI - A kinetic study of egg production, fecal egg output, and the rate of proglottid shedding in Hymenolepis nana. AB - To estimate the rate of shedding of the proglottids during normal development of Hymenolepis nana in mice, 2 parameters, i.e., egg production and fecal egg output, have been determined. Changes in the number of eggs/proglottid along the length of the worm showed that, not only in vitro but also in vivo, a considerable number of eggs is discharged in situ while the proglottids are still attached to the worm. The in situ egg discharge, however, accounts only for a small fraction of the eggs appearing in the feces, and it can be neglected in the estimation of the shedding of proglottids. In H. nana the larva rotates 90 degrees in the egg during its development. This seems to occur in a short period, quite in concert within each proglottid. The transition point (the proglottid where 50% of the eggs have begun rotating) can be a useful landmark to estimate the rate of proglottid shedding. Egg numbers at the transition points approximate the genuine egg production, because in situ egg discharge mostly occurs only after the proglottids have passed the transition point. The 3 processes, i.e., the rotation of the larva in the egg, the in situ egg discharge, and the shedding of proglottids, usually occur in an orderly way. However, on day 20 of infection, just before the worms are lost (or destrobilated), shedding of proglottids seems to be inhibited, whereas the other processes are apparently normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597796 TI - Susceptibility of Macaca fascicularis monkeys from Mauritius to different species of Plasmodium. AB - Macaca fascicularis monkeys from Mauritius were shown to be susceptible via sporozoite inoculation to 7 species of Plasmodium (P. fragile, P. coatneyi, P. gonderi, P. inui, P. cynomolgi, P. knowlesi, and P. fieldi), indigenous to macaques in southeastern Asia. Four monkeys were sequentially infected with different species of Plasmodium to determine maximum and course of parasitemia. In 2 nonsplenectomized monkeys, P. fragile developed maximum parasite counts of only 134 and 155/microliters. For Plasmodium knowlesi, a parasite that is life threatening to rhesus monkeys, maximum parasite counts were 4,278 and 7,440/microliters. Plasmodium coatneyi developed to what must be considered as moderate levels. After animals underwent splenectomy, parasite counts of P. coatneyi were 58,280, 89,094, 4,464, and 43,524/microliters. The maximum parasite counts for P. gonderi (13,508 and 21,576/microliters) and P. fieldi (1,767 and 17,836/microliters) were lower than would be expected in M. mulatta. In 2 monkeys that developed patent parasitemia with P. inui, the maximum parasite counts (95,046 and 728,748/microliters) indicated that this parasite may be the best adapted species for development in these animals once infection is established. Finally, the reinfection of 2 monkeys with P. cynomolgi suggested that some animals may be basically more resistant than others, whether splenectomized or not, to the production of high-density parasitemia. PMID- 1597797 TI - Effects of excretory-secretory products of Echinostoma paraensei larvae on the hematopoietic organ of M-line Biomphalaria glabrata snails. AB - Responses of the hematopoietic organ (HO) in Biomphalaria glabrata snails to extracts and excretory-secretory (E-S) products of Echinostoma paraensei larvae were studied to understand the HO-activating mechanism. M-line B. glabrata snails were injected with materials from E. paraensei larvae, and the size of the HO was ascertained in histological sections. The size of HO in snails injected with extracts and E-S products from sporocysts and rediae was significantly larger than that in snails injected with culture medium. E-S products of sporocysts were fractionated using ultrafiltration membranes, polyacrylamide gel electrophoresis, and electrophoretic elution. Examination of fractionated E-S products of sporocysts revealed that specific components of E-S products were responsible for HO-stimulating activity. PMID- 1597798 TI - Ultrastructure, antigenicity, and histochemistry of stichocyte granules of adult Trichinella spiralis. AB - The stichosome of adult Trichinella spiralis was studied to determine its ultrastructural, antigenic, and histochemical characteristics. Stichocytes of adult worms had 2 types of granules, type I and type II, the ultrastructure of which was different from those of muscle larvae. Both types of granules consisted of a membrane surrounding a homogeneous matrix, and type I granules were rounder than type II granules. Sera from C3H mice immunized against excretory-secretory products of muscle larvae produced positive immunostaining of type I but not type II granules. Differences in antigenicity were observed between larval and adult stichocyte granules; monoclonal antibodies against alpha-granules of muscle larvae failed to label the adult granules. Azan staining revealed a histochemical difference between larval and adult stichocytes; adult stichocytes stained yellow, whereas larval stichocytes are known to stain red or blue. Thus, the present contribution revealed the existence of 2 distinct types of stichocyte granules in adult T. spiralis and showed them to differ profoundly from those characterized previously in muscle larvae. PMID- 1597799 TI - Moniliformis moniliformis infection has no effect on some behaviors of the cockroach Diploptera punctata. AB - The behavior of the cockroach Diploptera punctata parasitized with the acanthocephalan Moniliformis moniliformis was examined for parasite-induced alterations. No significant difference in behavior was found between parasitized and unparasitized animals in the following behavioral tests: (1) choice of white/black, horizontal/vertical substrate under light and dark conditions; (2) temporal and directional response to a bright light source; (3) choice between light and dark (photophilia); and (4) activity (time spent moving, distance, and velocity). A comparison of uninfected animals under 2 light conditions showed that light affected the activity of uninfected animals and their response to substrate. Diploptera punctata is the first nondomestic cockroach to be examined for behavioral responses to Moniliformis infection. This is the first report of an arthropod in which acanthocephalan infection has failed to alter behavior under at least some common test conditions. PMID- 1597800 TI - Changes in fibroblast-derived trypomastigotes of Trypanosoma cruzi during long term culture. AB - Fibroblast-derived trypomastigotes (FDTs) of Trypanosoma cruzi that had been in culture for extended periods of time were found to differ in their ability to proliferate in culture when compared to blood-form trypomastigotes (BFTs) and FDTs that had been recently established from blood-forms. "Old" FDTs transform into amastigotes/spheromastigotes and epimastigotes and readily incorporate [3H]thymidine in medium alone or in the presence of mouse spleen cells, whereas "new" FDTs and BFTs did not incorporate [3H]thymidine although they did transform in culture. These differences should be considered when FDTs are used for physiologic and immunologic studies of T. cruzi. PMID- 1597801 TI - Comparison of Montana and Alaska isolates of Echinococcus multilocularis in gerbils with observations on the cyst growth, hook characteristics, and host response. AB - To assess its biological distinctness, an isolate of Echinococcus multilocularis from Montana was compared with an isolate from Alaska in gerbils (Meriones unguiculatus) by means of intraperitoneal inoculations with protoscoleces. The cysts formed by the Montana isolate were entire, hyaline, and translucent, whereas those produced by the Alaska isolate were granular, yellowish, and opaque. Vesicles of the Montana isolate were larger, produced protoscoleces more slowly but in greater numbers, and required a longer period to develop surfacial germ cell protrusions, which were of smaller size. Also delayed was invasion of the laminate layer by granulocytes and macrophages, and a longer time was required for the appearance of pulmonary metastases. The 2 isolates differed also in characteristics of rostellar hooks, those from the Montana isolate being fewer and larger, often with accessory hooks. PMID- 1597802 TI - Neospora caninum (Apicomplexa) in a stillborn goat. AB - Tissue cysts of Neospora caninum were found in sections of brain from a stillborn pygmy goat. The tissue cysts had 1-2-microns-thick cyst walls and stained with anti-N. caninum serum in an immunohistochemical test. Glial nodules, mononuclear perivascular cuffing, and foci of inflammation were associated with N. caninum tissue cysts throughout the brain. This report indicates that N. caninum can be transmitted transplacentally in goats. PMID- 1597803 TI - Activity of sulfadimethoxine against cryptosporidiosis in dairy calves. AB - Of 13 neonatal calves inoculated orally with 1.5 x 10(6) oocysts of Cryptosporidium parvum, 7 in group A were fed 5-g boluses of sulfadimethoxine for 21 consecutive days beginning 1 day before infection, and 6 calves in group B were untreated controls. Calves in group A had diarrhea for 6-18 days (mean = 11 days); those in group B had diarrhea for 4-14 days (mean = 8.7 days). The severity of diarrhea, based on a daily numerical scoring system, was similar for both groups. Calves in group A shed an average of 18 x 10(6) oocysts/ml of feces for 3.9 days; those in group B shed an average of 2.4 x 10(6) oocysts/ml of feces for 5.3 days. By 28 days of age, calves in group A vs. group B gained an average of 8.9 kg vs. 15.7 kg. These findings indicate that sulfadimethoxine did not significantly reduce the number of days or severity of diarrhea, or the number of oocysts or patent period, nor did it improve weight gains. PMID- 1597804 TI - Penetration of Eimeria tenella sporozoites under different oxygen concentrations in vitro. AB - Sporozoites of Eimeria tenella (Wisconsin strain) were inoculated onto monolayers of normal chicken kidney fibroblasts and cultured in RPMI-1640 supplemented with 5% fetal bovine serum, sodium bicarbonate, and gentamicin under either aerobic, 5% CO2/95% air, or anaerobic conditions. Penetration of fibroblasts by sporozoites under CO2 or anaerobic conditions at 2 and 24 hr postinoculation was 3-4 times greater than that in the aerobic atmosphere. Effect of reduced oxygen concentrations, i.e., 20.0, 12.5, and 5.0% oxygen, was also investigated in an N2 O2-CO2 incubator. Under 5.0 and 12.5% oxygen at 2 and 24 hr postinoculation, the number of sporozoites that penetrated was about 4 and 2 times greater, respectively, than under 20.0% O2. These results indicate that lower oxygen concentrations provide for greater penetration by E. tenella sporozoites in cultured cells. PMID- 1597805 TI - Prevalence of the nematode Spauligodon giganticus (Oxyurida: Pharyngodonidae) in neonatal Yarrow's spiny lizards, Sceloporus jarrovii (Sauria: Iguanidae). AB - Examination of the digestive tracts of 31 field-collected neonatal Sceloporus jarrovii Cope, 1875, estimated to be between 1 day and 2 wk of age revealed a prevalence of 74% (23/31) infection for eggs and/or larvae of the nematode Spauligodon giganticus (Read and Amrein, 1953) Skrjabin, Schikhobalova, and Lagodovskaja, 1960, and a prevalence of 3% (1/31) for the cestode Oochoristica sp. Twenty-two captive-born neonatal Sceloporus jarrovii, no older than 1 day revealed a prevalence of 14% for eggs of Spauligodon giganticus. Substrate licking, a behavior evident soon after birth, apparently is responsible for this almost immediate infection by S. jarrovii. PMID- 1597806 TI - Host records and tissue locations for Diplostomum mordax (metacercariae) inhabiting the cranial cavity of fishes from Lake Titicaca, Peru. AB - Metacercariae of Diplostomum mordax were found in the cranial cavity of Orestias agasii, Orestias olivaceous, Orestias luteus, and Basilichthys bonariensis, fishes from Lake Titicaca, Peru. Metacercariae were not found in Oncorhynchus mykiss introduced into the lake during 1939 and 1940. Compression of neural tissue within and on the surface of the brain was observed in all infected fishes. Metacercariae migrating into the cerebrum and cerebellum of the piscine host caused hemorrhaging, cell necrosis, inflammation, fiber formation, and nerve fiber disruption. The presence of D. mordax in B. bonariensis and the 3 species of Orestias constitute new host records. Infections in the cerebrum and cerebellum add new information on specific parasite location. PMID- 1597807 TI - Reciprocal translocation between the long arms of chromosomes four and six of Paragonimus westermani from the Philippines. AB - C-banding patterns have been observed in 14 specimens of Paragonimus westermani from Jaro, Leyte, the Philippines. One of them showed mutations of 2 chromosomes in spreads. Comparative analysis of C-banding patterns between the individual and standard type clarified that the mutant resulted from a reciprocal translocation between the long arms of chromosomes 4 and 6. PMID- 1597808 TI - Trypanosoma cruzi in wild raccoons and opossums in North Carolina. AB - Trypanosoma cruzi was isolated from 1 of 12 (8.3%) opossums and 3 of 20 (15%) raccoons from the piedmont area of North Carolina. Although T. cruzi has been isolated previously from wild mammals in the southern United States, the present study is the first published report of naturally occurring T. cruzi infection of wild mammals in North Carolina. All 4 isolates were maintained successfully in axenic culture and in murine fibroblasts. In addition, intraperitoneal injection of 1 x 10(6) culture forms of 1 of the opossum isolates into C3H mice resulted in low but detectable parasitemias as early as day 6 of infection. These mice resolved parasitemia and survived infection. Intraperitoneal injection of 1 x 10(6) culture forms of a raccoon isolate resulted in the death of 3 out of 4 mice. Surprisingly, parasitemias were never detected in the peripheral blood of these mice. Infection of murine fibroblasts in vitro resulted in the presence of intracellular amastigote stages characteristic of T. cruzi. PMID- 1597809 TI - A novel method for the isolation of nematode larvae using pluronic F-68-treated cellulose strips. AB - A new method is described for the isolation of cultured nematode larvae. This allows effective separation of larvae from fecal contamination, exsheathed larvae from cast sheaths, and viable larvae from nonviable larvae. The method involves the use of cellulose strips and has been assessed using larvae from 2 hookworm species, Necator americanus and Ancylostoma ceylanicum. Pretreatment of the cellulose strips with 1.0% (w/v) of the nonionic surfactant, Pluronic F-68, significantly increased larval recovery of both species. PMID- 1597810 TI - Effects of Pectenophilus ornatus (Copepoda) on the biomass of cultured Japanese scallop Patinopecten yessoensis. AB - There was a negative relationship between the number of parasitic copepods (Pectenophilus ornatus) and the dry weight condition index of the infected Japanese scallop (Patinopecten yessoensis) cultured in the Tsugaru Strait of northern Japan. The parasite is considered a serious pest of the commercial bivalve in cases of heavy infection. PMID- 1597811 TI - Alternative leech vectors for frog and turtle trypanosomes. AB - Trypanosoma pipientis infections were achieved by exposing laboratory-raised bullfrog tadpoles (Rana catesbeiana) to the leech Desserobdella picta that had fed on infected frogs. Likewise, a laboratory-raised snapping turtle (Chelydra serpentina) was infected with Trypanosoma chrysemydis following exposure to infected Placobdella ornata. Transmission of the trypanosomes by these leeches constitutes new vector records for the parasites. The biology of D. picta and P. ornata suggests that they are more important in transmitting these flagellates than the species of leech previously reported as vectors. PMID- 1597812 TI - Phylogeny of Plasmodium species: estimation and inference. PMID- 1597813 TI - Authorship--we need your expertise. PMID- 1597814 TI - Living with an unconventional child. AB - This article describes the child who experiences learning and living difficulties, both in the home and school environments. Understanding the family's feelings and providing practical, specific strategies for coping with emotional and behavioral manifestations of unconventionality enables professionals to offer not just empathy, but also viable, meaningful help. PMID- 1597815 TI - A home health record for children with chronic health conditions. AB - A Home Health Record was developed to assist parents in organizing health care information about their children who have disabilities or chronic health conditions. This record serves as a health summary to be used during travel, periods of respite care, and by grown children as they become independent health care consumers. It is intended to facilitate parent and professional collaboration, support family-centered care, and improve communication between professionals. Parents are encouraged to carry the record with them to all of their child's medical appointments to document pertinent information and to share health data with professionals. PMID- 1597816 TI - School-based clinics: the Baltimore experience. AB - Adolescents are at risk for a wide range of problems necessitating creative approaches to the delivery of health care. Baltimore City has responded to this challenge by opening seven school-based clinics (SBCs) that provide comprehensive health and social services to adolescents. This article summarizes the history of SBCs, the range of services, and the role of community involvement. A major focus of this article is the independent role of the nurse practitioner as clinical expert and educator. PMID- 1597817 TI - Child survival: what are the issues? AB - Five health problems continue to jeopardize the survival of the world's children including prenatal factors, level of nutrition, communicable diseases common to childhood, diarrheal diseases, and acute respiratory infections. Although some of these concerns are being managed effectively in the United States and other Western countries, they still pose tremendous risks for the child born in Asia, Africa, Latin America, or the South Pacific. PMID- 1597818 TI - Care of HIV-risk infants: nursing outreach by PNPs. AB - In this prospective study, HIV-risk infants (infants born to women with a history of intravenous drug use, prostitution, or who is a sexual partner of an intravenous drug user) were followed during home visits by a pediatric nurse practitioner. Analysis of home visit records indicated that significant medical problems were detected in one out of every 12 visits, requiring referral of the infant for immediate medical attention. The most frequent problems/maternal concerns encountered during the home visits were infectious disease symptoms and skin conditions. The type of problems/maternal concerns did not differ by infant HIV status. With an increase in incidence of HIV infection in children, outreach by specialized nurses including PNPs is necessary to provide the intensive medical services required by these children. PMID- 1597819 TI - Management and counseling of children with inherited metabolic disorders. AB - Although rare individually, as a group inborn errors of metabolism are relatively common in the pediatric population. Families need assistance with evaluation and referral, accurate counseling, and management issues. An overview of inherited metabolic disorders is presented, followed by discussion and examples of selected categories of disease. PMID- 1597820 TI - Teething. PMID- 1597821 TI - Health care for children. PMID- 1597822 TI - A new area in which pediatric nurse practitioners can contribute to the care of children. PMID- 1597823 TI - Pallor and pica. PMID- 1597824 TI - Talk about death and dying: it's the law. PMID- 1597825 TI - Playground safety. PMID- 1597826 TI - NAPNAP president's message. Address unknown: the homeless. PMID- 1597827 TI - The medial heel skive technique. Improving pronation control in foot orthoses. AB - A new method of foot orthosis modification that enhances the pronation controlling ability of foot orthoses is presented. The medial heel skive technique involves selectively removing small amounts of the medial portion of the plantar heel of the positive cast of the foot to create a unique varus wedging effect within the heel cup of the foot orthosis. The resulting increase in supination moment across the subtalar joint axis of the foot clinically produces significantly improved pronation control on pediatric flexible flat feet, posterior tibial dysfunction, and other types of excessively pronated feet. PMID- 1597828 TI - Leriche's syndrome. AB - Leriche's syndrome will be seen by the podiatric physician, and it can be misinterpreted as pain secondary to mechanical etiology. Often, symptoms of buttock or thigh pain occurring during walking resemble those seen with symptomatic pronation, so this disease entity must be ruled out. PMID- 1597829 TI - Extrinsic rearfoot posts. AB - The addition of an extrinsic rearfoot post to an orthotic device allows the podiatric practitioner to modify the function of the device. Specifically, rearfoot posts are used to allow for a more inverted heel position at contact, to provide greater resistance to abnormal frontal plane motion of the calcaneus and to provide for motion for shock absorption. The authors present nine prescription variables that each provide for a specific functional change to be incorporated into the orthotic device. PMID- 1597831 TI - Nodular malignant melanoma. PMID- 1597830 TI - Giant cell tumor of the intermediate cuneiform. A case report. AB - Although it has yet to be determined which surgical procedure provides the least chance for recurrence, surgical treatment remains the preferred therapy for giant cell tumors of bone. Few cases of giant cell tumor of the tarsus have been reported in the literature, with less than 10 of these cases occurring in the cuneiforms. When the extent of the tumor is questionable, definitive radiologic techniques should be used to aid in the selection of the most appropriate surgical procedure. Follow-up radiographic examination is critical to ensure that the patient remains tumor free. Yearly chest x-rays are recommended to rule out pulmonary metastasis. Although giant cell tumors represent only 5% to 8% of all benign primary osseous neoplasms of the foot, they have the potential to undergo malignant transformation, increasing the morbidity and mortality to the patient. Giant cell tumors of bone are locally aggressive, often occurring adjacent to articular surfaces, and usually are large when diagnosed. It is essential for the surgeon to plan a treatment that not only minimizes the chance of recurrence, but also attempts to preserve function of the involved part. PMID- 1597832 TI - An unusual presentation of a periungual fibroma. PMID- 1597833 TI - Traumatic inclusion cyst versus pilar cyst of the foot. PMID- 1597834 TI - Prevalence of chronic podiatric conditions in the US. National Health Survey 1990. PMID- 1597836 TI - Liver and biliary problems in cystic fibrosis. PMID- 1597835 TI - Gastrointestinal complications in cystic fibrosis. PMID- 1597837 TI - Diabetes mellitus in cystic fibrosis: a review. PMID- 1597838 TI - ENT surgery and cystic fibrosis. PMID- 1597839 TI - Cystic fibrosis and pregnancy. PMID- 1597840 TI - Vasculitis and arthropathy in cystic fibrosis. PMID- 1597841 TI - Cystic fibrosis: lung transplantation. A new option--a new dilemma! PMID- 1597842 TI - Lifestyles, glucose tolerance and blood pressure in male self-defence officials in northern Kyushu, Japan. AB - Evidence on determinants of BP is mostly derived from studies in western populations. The relationship of BP with lifestyle variables and glucose tolerance was studied in 1,302 male self-defence officials aged 49-56 years who received a health examination before retirement at the Self-Defense Forces Fukuoka Hospital from October 1986 to December 1988. Those with treated hypertension or diabetes mellitus and those with conditions affecting BP levels were excluded from the study. In multiple regression analysis, alcohol use, body mass index and glucose intolerance were strongly associated with elevated BP while there was an inverse relation between cigarette smoking and BP. Physical activity expressed as the time spent in vigorous exercise was not associated with either systolic or diastolic BP. These findings indicate that alcohol use, obesity and glucose intolerance are also important determinants of BP in male Japanese, and that cigarette smoking is a potential covariate in the study of BP. PMID- 1597843 TI - Environmental and genetic factors of hypertension in a biracial Beduin population. AB - This study attempts to understand the various factors involved in the pathophysiology of hypertension in black Beduins. Parameters known to differentiate US black from white hypertensives were examined. Sixty Beduin families (thirty families each of black and white, total of 205 subjects) were evaluated for environmental risk factors: a traditional nomad shepherd life-style compared with working in a city, living in tents or in western style housing and dietary habits related to cardiovascular risk factors. Blood pressure, body mass index (BMI), sodium-lithium counter transport rate and 24 hour urinary sodium excretion (UNa) were measured and the data obtained were compared between normotensives and hypertensives, within each racial group. The mean value of the BMI of the white population was greater than that of the black population while the BMI of hypertensives was greater than that of the normotensives in each of the racial groups. The mean systolic BP of black hypertensives was greater than that of the corresponding whites. There were no significant differences in UNa between the four groups. Sodium-lithium countertransport was significantly higher in the hypertensive whites compared with the normotensive population (0.46 versus 0.22 mmol Li efflux/IRBC/hr). The countertransport rate for black hypertensives was lower than that of white hypertensives (0.20 versus 0.46). Black families had lower socio-economic scores than did white families and families with a hypertensive member scored lower than did families with a normotensive history. These results demonstrate some similarities between the American and Beduin black hypertensive populations, in spite of entirely different life-styles, indicating that in these populations genetic factors, rather than environmental influences, appear to be dominant in the pathophysiology of hypertension. PMID- 1597844 TI - The antihypertensive effect of dietary supplementation with a 6-desaturated essential fatty acid concentrate as compared with sunflower seed oil. AB - There is increasing evidence that the type of fat in the diet may play a role in the control of blood pressure and development of hypertension. The purpose of the present study was to investigate the effect of a concentrated preparation of the 6-desaturated essential fatty acids gamma-linolenic acid (C18:3n-6), eicosapentaenoic acid (C20:5n-3) and docosahexaenoic acid (C22:6n-3) on individuals with raised BP. Eighteen volunteers from our College staff with elevated BP on several occasions but otherwise healthy, were divided into two groups following a two-week baseline period. One group received 4g sunflower seed oil daily and the other 4g of an oil preparation rich in C18:3n-6, C20:5n-3 and C22:6n-3 for six weeks. Major measurements included BP and fatty acids in phospholipids and cholesteryl esters. Dietary intakes and urinary fluid and electrolyte excretion were also monitored during baseline and intervention periods. The subjects' office diastolic BP showed a significantly greater effect of the concentrate over the sunflower seed oil, both overall (P = 0.03) and in interaction with time (P = 0.012). Fatty acids in plasma cholesteryl esters underwent mild alterations following the administration of the concentrate. There were no important changes in nutrient intakes or in sodium, potassium and fluid excretion during the trial period. PMID- 1597845 TI - Captopril therapy in severe hypertension: effects of intravenous administration. AB - In 10 severe hypertensives the effects of intravenous administration of scalar doses of captopril were evaluated. The behaviour of blood pressure, heart rate, electrocardiographic pattern and left ventricular (LV) diastolic function, in basal condition (T0) and after 60 min of captopril infusion (T60), were analysed. Diastolic performance was assessed by pulsed wave Doppler echocardiography, evaluating transmitral peak flow velocities in early diastole (PEDV), late diastole (PLDV) and the PEDV/PLDV ratio. All patients showed an increase in LV mass (assessed by M-mode echocardiography) and altered diastolic performance, documented by high PLDV and low PLDV/PEDV ratio values. Clinical, haematological, urinary and biochemical data were also assessed for possible side effects. Captopril significantly reduced BP in 7 out of the 10 patients. Supine BP decreased from 212 +/- 15.3/126 +/- 5.6 to 171 +/- 17.7/98 +/- 11.8 mmHg (T0 vs. T60 P less than 0.0001). No electrocardiographic abnormality was observed during the study. The goal of antihypertensive effect was reached at 40-50 min after the onset of captopril therapy. Heart rate showed a small but constant decrease (from 76 +/- 7.7 to 72.8 +/- 5.7 beats/min, T0 vs. T60, P less than 0.05). Side effects of intravenous captopril were always mild and transient; no severe hypotension as 'first dose effect' was observed in our study. The echocardiographic data showed a significant decrease in LV end-systolic dimension after captopril infusion, while left atrial, LV diastolic dimension and fractional shortening remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597846 TI - A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension. AB - A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597847 TI - Effects of nicardipine on the metabolic responses to food and exercise. AB - In a placebo-controlled, double-blind, randomised, cross-over study the metabolic and hormonal responses to standard food and exercise challenge have been evaluated in seven patients with mild to moderate essential hypertension after treatment with nicardipine 30 mg three times daily for four weeks. There were no significant differences between nicardipine and placebo for any of the measured hormonal and metabolic indices following food or exercise. These results indicate that nicardipine has no clinically important effects on serum lipids or hormonal or metabolic responses to food and exercise. PMID- 1597848 TI - Decreased exercise capacity in mild essential hypertension: non-invasive indicators of limiting factors. AB - Available data suggest that exercise capacity is limited in hypertension. The mechanism of this reduced maximal exercise capacity has not been fully elucidated. In this study 22 patients with mild essential hypertension (162 +/- 22 mmHg systolic and 95 +/- 8 mmHg diastolic) and 36 normotensive control subjects (128 +/- 13 mmHg systolic and 80 +/- 7 mmHg diastolic) (P less than 0.01) performed an ergometer test till exhaustion. Body mass index in the two groups did not differ. The maximal oxygen consumption VO2 was lower in the hypertensive group (18 +/- 7 versus 23 +/- 8 ml/kg/min; P less than 0.02) as was the maximal workload (141 +/- 52 vs. 185 +/- 70 Watt; P less than 0.01). Rate pressure product rose only 2.7 fold in hypertensive patients versus 3.5 fold in the control group (P less than 0.001). In hypertensive patients maximal workload decreased with increasing resting systolic blood pressure (P less than 0.05) while in the normotensive subjects maximal workload rose with increasing resting systolic blood pressure (P less than 0.05). In conclusion both high and low blood pressure was associated with a decreased maximal voluntary exercise capacity. Even mild hypertension was accompanied by lower maximal exercise capacity. Hypertensive patients also had a lower maximal VO2 and lower maximal rate pressure product than did normotensive subjects. PMID- 1597849 TI - Casual urine concentrations of sodium and potassium and geographic blood pressure variations in Great Britain. AB - The associations between blood pressure and urine sodium, potassium and creatinine have been studied among 1,240 men and 1,119 women living in nine British towns in order to assess the contribution of sodium and potassium intake to geographic BP variations within Great Britain. Significant positive associations were found between systolic BP and the urine sodium/potassium ratio for men (P less than 0.05) and for women (P less than 0.001), and for the sodium/creatinine ratio in men (P less than 0.01), after adjustment for age and body mass index. The findings for diastolic BP were similar, but non-significant for men. Associations between BP and sodium concentration were inconsistent and non-significant. The associations between BP and potassium concentration were consistently negative, and significant for diastolic in women (P less than 0.01). The correlations between the mean town systolic BPs and the sodium/potassium ratio were 0.65 (P = 0.058) for men, and 0.60 (P = 0.086) for women. Correlations for diastolic BP were such smaller. The association between BP and the sodium/potassium ratio in this study is consistent both within and between populations, although more so for women than for men. The results are also consistent with the results of other population studies using casual and 24 urine specimens. Although unable to quantify the effects of sodium and potassium with precision, the study suggests that the sodium/potassium ratio is of importance in geographic BP variations in Great Britain, at least for systolic blood pressure. PMID- 1597850 TI - Accelerated hypertension caused by severe phimosis. AB - A 16 year old boy presented with accelerated hypertension and urinary tract obstruction caused by phimosis. Relief of the obstruction by circumcision reversed the hypertension. We believe that accelerated hypertension secondary to phimosis has not previously been described. PMID- 1597851 TI - Ambulatory blood pressure is still elevated in treated hypertensive diabetic subjects compared with untreated diabetic subjects with the same office blood pressure. AB - Ambulatory blood pressure, ABP, was determined every 15 min for 24 h (Spacelabs 5200 system) in 16 hypertensive diabetic subjects treated for high blood pressure. Office blood pressure (OBP) in these subjects (systolic BP greater than 160 mmHg and diastolic BP greater than 95 mmHg before treatment) had been reduced by treatment to the borderline range (systolic less than or equal to 160 mmHg and/or diastolic less than or equal to 95 mmHg). Sixty-five diabetic subjects with normal or borderline OBP were included as controls. The two groups had the same age (58 +/- 10 yrs in both groups), duration of diabetes (15 +/- 9 yrs), 24 hr microalbumin, and included the same percentage of subjects with moderate neuropathy (36% and 29%, NS). The two groups had the same OBP (138 +/- 16 mmHg and 140 +/- 16 mmHg systolic, NS, 84 +/- 9 mmHg and 84 +/- 13 mmHg diastolic, NS). In contrast, ambulatory BP was significantly higher in the treated group, when compared with the controls (123 +/- 13 mmHg and 133 +/- 23 mmHg systolic, P less than 0.025, 77 +/- 7 mmHg and 84 +/- 16 mmHg diastolic, P less than 0.015). The difference was significant both in daytime and in nighttime, and was more significant in nighttime (11 mmHg systolic, P less than 0.02, 9 mmHg diastolic, P less than 0.004) than in daytime (9 mmHg systolic, P less than 0.05 and 5 mmHg diastolic, P less than 0.05). Ambulatory heart rate was also significantly higher in the treated group, but only in daytime (7 b/min difference, P less than 0.02). The study demonstrated the need to survey and investigate ABP in treated hypertensive diabetic subjects. PMID- 1597852 TI - Haemodynamic effects of coffee and purified caffeine in normal volunteers: a placebo-controlled clinical study. AB - In order to evaluate the effects of 'espresso' Italian coffee on resting flow, blood pressure, and peripheral resistance, 15 non-coffee drinking healthy volunteers received 2 cups of regular coffee, 200 mg purified caffeine or placebo in a latin square double-blind crossover protocol. Before and 30, 60, 90 and 120 min after ingestion, segmental resting flow and BP were measured and peripheral resistance was calculated. An echocardiogram was also performed before and 60 and 120 min after caffeine intake. Both regular coffee and caffeine produced a significant decrease in resting flow and a significant increase in resistance; both systolic and diastolic BP also increased, although not significantly. No variation was observed in heart rate and in cardiac contractility. Placebo (highly decaffeinated coffee for regular coffee and china bitter extract for caffeine) did not produce any haemodynamic effect. In five other healthy volunteers used to drinking more than 5 cups of coffee a day, coffee administration had no effect. These data demonstrate that the caffeine contained in espresso Italian coffee is a vasoconstrictor agent whose effects however are completely blunted in usual coffee drinkers as a consequence of adaptation. PMID- 1597853 TI - A nonpromoting phorbol from the samoan medicinal plant Homalanthus nutans inhibits cell killing by HIV-1. AB - Extracts of Homalanthus nutans, a plant used in Samoan herbal medicine, exhibited potent activity in an in vitro, tetrazolium-based assay which detects the inhibition of the cytopathic effects of human immunodeficiency virus (HIV-1). The active constituent was identified as prostratin, a relatively polar 12 deoxyphorbol ester. Noncytotoxic concentrations of prostratin from greater than or equal to 0.1 to greater than 25 microM protected T-lymphoblastoid CEM-SS and C 8166 cells from the killing effects of HIV-1. Cytoprotective concentrations of prostratin greater than or equal to 1 microM essentially stopped virus reproduction in these cell lines, as well as in the human monocytic cell line U937 and in freshly isolated human monocyte/macrophage cultures. Prostratin bound to and activated protein kinase C in vitro in CEM-SS cells and elicited other biochemical effects typical of phorbol esters in C3H10T1/2 cells; however, the compound does not appear to be a tumor promoter. In skin of CD-1 mice, high doses of prostratin induced ornithine decarboxylase only to 25-30% of the levels induced by typical phorbol esters at doses 1/30 or less than that used for prostratin, produced kinetics of edema formation characteristic of the nonpromoting 12-deoxyphorbol 13-phenylacetate, and failed to induce the acute or chronic hyperplasias typically caused by tumor-promoting phorbols at doses of 1/100 or less than that used for prostratin. PMID- 1597854 TI - Asymmetric synthesis of 1,3-dioxolane-pyrimidine nucleosides and their anti-HIV activity. AB - In order to study the structure-activity relationships of dioxolane nucleosides as potential anti-HIV agents, various enantiomerically pure dioxolane-pyrimidine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear cells. The enantiomerically pure key intermediate 8 has been synthesized in nine steps from 1,6-anhydro-D-mannose (1), which was condensed with 5-substituted pyrimidines to obtain various dioxolane-pyrimidine nucleosides. Upon evaluation of these compounds, cytosine derivative 19 was found to exhibit the most potent anti-HIV agent although it is the most toxic. The order of anti-HIV potency was as follows: cytosine (beta-isomer) greater than thymine greater than cytosine (alpha-isomer) greater than 5-chlorouracil greater than 5-bromouracil greater than 5-fluorouracil derivatives. Uracil, 5 methylcytosine, and 5-iodouracil derivatives were found to be inactive. Interestingly, alpha-isomer 20 showed good anti-HIV activity without cytotoxicity. As expected, other alpha-isomers did not exhibit any significant antiviral activity. (-)-Dioxolane-T was 5-fold less effective against AZT resistant virus than AZT-sensitive virus. PMID- 1597856 TI - Ester and amide derivatives of E64c as inhibitors of platelet calpains. AB - Ester and amide derivatives of E64c, (+)-(2S,3S)-3-[[(S)-3-methyl-1- [(3 methylbutyl)carbamoyl]butyl]carbamoyl]-2-oxiranecarboxylic acid, an inhibitor of calpains, were synthesized and tested for ability to inhibit calpain in lysed cells, ability to enter intact cells, and ability to inhibit calpain in intact cells. The esters were from halogen-substituted alcohols and alcohols with increasing size. There were no appreciable differences in the inhibitory potency of any of the halogen-substituted esters from ethyl to trifluoroethyl, indicating that ease of hydrolysis of this class of ester is not important for activity. The only ester with impaired activity was the largest, Z-leucyl-norleucyl, which was about 5% as effective as the ethyl ester, E64d. Amides of amino acid esters also had impaired activity. To explore the possibility of targeting E64c derivatives to specific cells, esters and amides of E64c with 5-hydroxytryptamine were tested on the rationale that the active 5-hydroxytryptamine uptake mechanism of platelets might selectively concentrate the drug in platelets. Both the ester and amide inhibited calpain in lysed cells, but only the ester inhibited in intact cells. The 5-hydroxytryptamine ester showed no advantage over the ethyl ester in entering platelets. PMID- 1597855 TI - Cyclic RGD peptide analogues as antiplatelet antithrombotics. AB - Stimulation of platelets activates GPIIbIIIa, the heterodimeric integrin receptor, to bind fibrinogen (Fg), which results in platelet aggregation. GPIIbIIIa/Fg binding inhibitors are potentially suitable for acute use during and after thrombolytic therapy as antithrombotic agents. Incorporation of the tripeptide sequence Arg-Gly-Asp (RGD), a common structural element of many integrin ligands, into cyclic peptides produced a series of peptides of the general structure BrAc-(AA1)-RGD-Cys-OH, which were prepared by solid-phase peptide synthesis. Cyclization was accomplished by reaction of the N-terminal bromoacetyl group with the cysteine sulfhydryl at pH 8 at high dilution, resulting in thioether-bridged cyclic peptides [cyclo-S-Ac-(AA1)-RGD-Cys-OH]. Use of alpha-substituted bromoacetyl groups gave rise to an analogous series of acetyl-substituted thioether-bridged cyclic peptides. Oxidation of the thioethers produced separable diastereomeric sulfoxide-bridged cyclic peptides. After thorough evaluation in a GPIIbIIIa ELISA assay and a platelet aggregation assay, G-4120 (70A; AA1 = D-Tyr; sulfoxide bridge) was selected for further investigation as an antithrombotic agent. G-4120 was equipotent in the platelet aggregation assay to kistrin, a highly potent inhibitor of fibrinogen-mediated platelet aggregation isolated from snake venom (IC50 = 0.15 microM). PMID- 1597857 TI - Enzymatic synthesis and comparative biological evaluation of a phosphonate analogue of the lipid A precursor. AB - Phosphonate analogue 5 of the lipid A precursor 4 has been prepared from phosphonate 2 and nucleotide 3 with the help of lipid A synthase, isolated from the overproducing Escherichia coli mutant MC 1061 (delta 2512) or JB1104 (delta 2514). The biological properties of phosphonate 5 and phosphate 4 are quite similar to each other as compared in the limulus amoebocyte lysate assay, by the activation of the RAW264 murine macrophagelike cell line (determined by stimulation of ornithine decarboxylase), and by the pyrogenicity in rabbits. Hydrolytic removal of the 1-phosphate group of 4 is thus not a prerequisite for its biological activity. PMID- 1597858 TI - Biological activities and quantitative structure-activity relationships of spiro[imidazolidine-4,4'(1'H)-quinazoline]-2,2',5(3'H)-triones as aldose reductase inhibitors. AB - A series of spiro[imidazolidine-4,4'(1'H)-quinazoline]- 2,2'5(3'H)-triones were prepared and tested for aldose reductase inhibitory activity. The 6'-halogenated derivatives were found to be highly potent in vitro inhibitors of male rabbit lens aldose reductase and in vivo inhibitors of polyol accumulation in the sciatic nerves of galactosemic rats. Of these, (4R)-6'-chloro-3' methylspiro[imidazolidine-4,4'(1'H)-quinazoline] -2,2',5(3'H)-trione (67) showed the most potent in vitro and in vivo activities. An oral dose of 3 g/kg of compound 67 caused neither death nor behavioral abnormality in the preliminary acute toxicity study using mice and rats. Compound 67 was selected as a candidate for further evaluation. The quantitative structure-activity relationships in this series are also discussed. PMID- 1597859 TI - Inhibitors of cholesterol biosynthesis. 6. trans-6-[2-(2-N-heteroaryl-3,5 disubstituted- pyrazol-4-yl)ethyl/ethenyl]tetrahydro-4-hydroxy-2H-pyran-2-ones. AB - A series of N-heteroaryl-substituted mevalonolactones were prepared and evaluated for their ability to inhibit the enzyme HMG-CoA reductase both in vitro and in vivo, and to lower plasma cholesterol in a hypercholesterolemic dog model. The goal of the strategy employed was to design an inhibitor which possessed the pharmacological properties of lovastatin (1), and the physicochemical properties (increased hydrophilicity) of pravastatin (2). Two compounds 20a and 20b, were more potent than lovastatin at inhibiting cholesterol biosynthesis both in vitro and in vivo. In terms of plasma cholesterol lowering, 20a was much more efficacious than lovastatin. In addition to possessing increased biological activity, these compounds are significantly less lipophilic than lovastatin, in fact, 20b has a CLOGP value comparable to pravastatin. PMID- 1597860 TI - Renin inhibitors containing C-termini derived from mercaptoheterocycles. AB - A series of transition-state analogues having heterocyclythio C-termini has been synthesized and evaluated for inhibition of human renin. Addition of mercaptoheterocycles to a chiral Boc-amino epoxide intermediate led, after several steps, to the target [(2R,3S)-3-(BocPheHis-amino)-4-cyclohexyl-2-hydroxy 1-butyl]thio derivatives. Oxidation of the thioether to sulfone was also investigated. Several of the compounds, especially those derived from N1 substituted-5-mercaptotetrazoles or N4-substituted-3-mercapto-5-(trifluoromethyl) 1,2,4-triazoles, were moderately potent inhibitors of human plasma renin, having IC50 values of 30-40 nM. When selected compounds were administered intravenously to sodium-deficient rhesus monkeys at 0.3-1.2 mg/kg, they reduced plasma renin activity by 75-98%. However, this inhibition and the accompanying drop in blood pressure were of short duration. PMID- 1597861 TI - Synthesis of high affinity fluorine-substituted ligands for the androgen receptor. Potential agents for imaging prostatic cancer by positron emission tomography. AB - We have prepared nine androgens substituted with fluorine at C-16 or C-20 to evaluate their potential, as positron emission tomographic (PET) imaging agents for prostatic cancer when labeled with the positron emitting radionuclide fluorine-18 (t1/2 = 110 min). These compounds represent members from the following classes of androgens: testosterone (T), 5 alpha-dihydrotestosterone (DHT), 7 alpha-methyl-19-nortestosterone (MNT), mibolerone (Mib), and metribolone (R1881). All of these compounds were prepared by functionalization of suitable androgen precursors, and the synthetic routes were developed to allow the introduction of fluorine by a fluoride ion displacement reaction late in the synthesis, as is required for the preparation of these compounds in fluorine-18 labeled form. We have also prepared four androgens in which the C-3 carbonyl or 17 beta-hydroxyl groups are replaced by fluorine. Most of the fluorine substituted androgens show high affinity for the androgen receptor (AR), although fluorine substitution lowers their affinity by a small factor. None of the androgens where fluorine replaces oxygen functions at C-3 or C-17 have substantial affinity for AR. Derivatives of the natural androgens (T and DHT) as well as MNT have little affinity for other steroid hormone receptors (progesterone and mineralocorticoid receptors), whereas the Mib and R1881 derivatives have somewhat greater heterologous binding. With sex steroid binding protein, a human serum binding protein, the pattern of binding affinities is nearly the reverse, with derivatives of Mib, R1881 and MNT having low affinity, and DHT and T, high affinity. From these fluorine-substituted compounds, we can select several whose preparation in fluorine-18 labeled form for further tissue distribution studies is merited. PMID- 1597862 TI - Bisquinolines. 1. N,N-bis(7-chloroquinolin-4-yl)alkanediamines with potential against chloroquine-resistant malaria. AB - On the basis of observations that several bisquinolines such as piperaquine possess notable activity against chloroquine-resistant malaria, 13 N,N-bis-(7 chloroquinolin-4-yl)alkanediamines were synthesized and screened against Plasmodium falciparum in vitro and Plasmodium berghei in vivo. Twelve of the thirteen bisquinolines had a significantly lower resistance index than did chloroquine; the resistance index was apparently unrelated to either in vitro or in vivo activity. Except for two compounds, there was a reasonable correlation between in vitro and in vivo activities. Seven of the thirteen bisquinolines had IC50's of less than 6 nM against both chloroquine-sensitive (D-6) and -resistant (W-2) clones of P. falciparum and were curative against P. berghei at doses of 640 mg/kg. In contrast to chloroquine, these bisquinolines did not show any toxic deaths at curative dose levels. Four bisquinolines, however, caused skin lesions at the site of injection. Maximum activity was seen in bisquinolines with a connecting bridge of two carbon atoms where decreased conformational mobility seemed to increase activity. Bisquinoline 3 (+/-)-trans-N1,N2-bis(7 chloroquinolin-4-yl)cyclohexane-1,2-diamin e was not only the most potent bisquinoline in vitro, but was clearly unique in its in vivo activity--80% and 100% cure rates were achieved at doses of 160 and 320 mg/kg, respectively. In summary, these preliminary results support the premise that bisquinolines may be useful agents against chloroquine-resistant malaria. PMID- 1597863 TI - Clinical analysis by 1H spin-echo NMR. 2. Oxidation of intracellular glutathione as a consequence of penicillamine therapy in rheumatoid arthritis. AB - Spin echo NMR analysis is used to monitor the effect of penicillamine on intact erythrocytes obtained from patients suffering from rheumatoid arthritis during a 12-week period of therapy. The results are compared to the previously reported in vitro effects of the compound (McKay, C. N. N.; et al. Biochim. Biophys. Acta 1986, 888, 30-35). At clinical assessment at week 12, the 20 patients were divided into responder and nonresponder groups. The intracellular glutathione in the responder group is more oxidized (P less than 0.01) than in the nonresponder group. A retrospective analysis of the two patient groups at the initial assessment following the commencement of therapy indicated that in the nonresponder group intracellular glutathione was significantly more reduced (P less than 0.02) than in the responder group. It is postulated that penicillamine stimulates cellular defense against the oxidation of the cell membrane at the expense of cytosolic glutathione. This initial study suggests that spin-echo NMR analysis of erythrocyte glutathione can act as an early indicator of a clinical response to penicillamine therapy. PMID- 1597864 TI - p-(Methylsulfinyl)phenyl nitrogen mustard as a novel bioreductive prodrug selective against hypoxic tumors. PMID- 1597865 TI - Acute retinal necrosis syndrome. AB - 1. Acute retinal necrosis (ARN) represents a specific pattern of clinical presentations for certain herpes virus infections in the posterior segment of the eye. These include varicella zoster virus and herpes simplex virus. 2. Patients with ARN usually complain of mild to moderate ocular or periorbital pain, foreign body sensation, and a red eye. Visual symptoms usually include hazy vision, floaters, and, rarely, decreased peripheral vision. 3. Medical treatment of choice is intravenous acyclovir. Surgical treatment of choice is pars plana vitrectomy. If retinal detachment is present, vitrectomy with endolaser, internal drainage of subretinal fluid, air-fluid exchange, and long-acting gas tamponade are recommended. PMID- 1597866 TI - Low vision rehabilitation: vision requirements for driving. AB - Driving requires several different sets of abilities, the interaction of which is complex. The combination of these factors, rather than any single factor alone, may make it inadvisable to issue a driver's license. Although vision is the predominant source of information for the driver, visual abilities are only one of the factors to be considered when judging the overall driving ability of an applicant. The final determination can only be made through on-the-road evaluation and cannot be based on the evaluation of vision alone. Individual evaluations should include a review of the past driving record and of nonvisual driving-related abilities, as well as observation of on-the-road performance by a qualified driving instructor or driving evaluator. PMID- 1597868 TI - Hiring and training a contact lens technician. PMID- 1597867 TI - Fundus photograph of the patient's left eye revealing macular degeneration and laser scar. PMID- 1597869 TI - Notes on nursing. PMID- 1597870 TI - Perioperative nursing in the Third World: improvise without compromise. AB - 1. The reality of nursing in the Third World is a severe limitation of human, fiscal, and environmental resources. Our plan was to overcome these obstacles and establish a plan and perform outpatient eye surgeries. 2. The biggest obstacle was a lack of acceptance of the outpatient concept and many cultural differences. Native team members became excited about the concept when they saw positive results and the effectiveness of care. 3. Today, well-trained ophthalmic nurses are performing perioperative nursing in their native setting; they have become self-sufficient, independent workers; they are teaching other native nurses; and outpatient surgery is being performed daily. PMID- 1597871 TI - Case-control studies of severe malaria. AB - The majority of children infected with Plasmodium falciparum in areas of stable endemicity do not develop severe, life-threatening disease. It is important to identify risk factors for the minority who do. Case-control studies in which children with severe disease are compared with children with non-severe disease and with community controls, avoid some of the ethical and logistical problems inherent in such an undertaking. This paper discusses methodological aspects of case-control studies of severe malaria including case and control definitions, selection of cases and controls, potential risk factors, sample size calculations and analysis. Although specifically concerned with malaria, many of these issues are equally relevant to case-control studies of other infectious and parasitic diseases in a tropical environment. PMID- 1597872 TI - Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions. AB - Since the time of its introduction in 1985, mefloquine (Lariam) has been used extensively for malaria prophylaxis. The international Drug Safety Department of the manufacturer gathered all spontaneous adverse drug reactions reported in association with this drug from all available sources and monitored the literature on a world-wide basis. The serious neurologic and psychiatric adverse events reported in association with Lariam prophylaxis from the time of introduction until May 1991 were reviewed. During this time, 59 serious neurologic and psychiatric adverse reactions were reported as follows: 26 convulsions, 12 depressions, 20 psychotic episodes, and one toxic encephalopathy; none were fatal. While spontaneous reporting systems are biased by under reporting, they provide useful instruments for analysis of clinical risks factors. The neurologic and psychiatric adverse events reported in association with mefloquine prophylaxis were of the same types as those reported with other quinine derivative antimalarials. The precise mechanism of serious neurologic and psychiatric reactions is unknown. The only patient population identified at this time as having an increased risk of developing these serious reactions to mefloquine are persons with a history of seizures or manic-depressive illness. Mefloquine prophylaxis should not be prescribed to such patients. PMID- 1597873 TI - Childhood bacterial meningitis in Al-Baha province, Saudi Arabia. AB - A retrospective review of 71 paediatric patients admitted with bacterial meningitis to the King Fahad Hospital at Al-Baha, Saudi Arabia, during an 8-year period revealed a preponderance of males (67.6%) and young subjects with 88.7% being below 24 months of age. The commonest cerebrospinal fluid pathogens in the series were Haemophilus influenzae type B (HIB), Streptococcus pneumoniae and Group B-beta haemolytic streptococcus, which were responsible for 47.3, 34.5 and 9.1% of cases respectively. Neisseria meningitidis which is a major cause of meningitis in most other reports was uncommon in the present series, and was isolated from only two patients. All the children with Group B-beta haemolytic streptococcal meningitis were below 3 months of age while 96.2% of the children with HIB meningitis were younger than 2 years. Mortality was highest (40%) among the infants with Group B-beta haemolytic streptococcal meningitis. Six (23.1%) of the HIB isolated were resistant to ampicillin and two (7.7%) were resistant to both ampicillin and chloramphenicol. There is a need for greater emphasis on prevention through the use of available vaccines including the newly introduced conjugate vaccines against HIB which are capable of eliciting immune responses in infants as young as 2 months. PMID- 1597875 TI - Peripartum cardiac failure in The Gambia. AB - Twenty-seven patients with peripartum cardiac failure were seen at the Royal Victoria Hospital, Banjul over a 2-year period while one further patient presented 6 months after delivery with a cerebral embolus secondary to a dilated cardiomyopathy. Five (18%, P less than 0.001) patients had twin pregnancies. Seventeen (63%) patients attended for follow-up, of whom eight had evidence of continuing cardiac dysfunction and required treatment with diuretics; two patients were known to have died. In five asymptomatic patients the electrocardiogram had reverted to normal and three patients had further pregnancies without relapse. The bipolar distribution of onset of symptoms in relation to pregnancy was suggestive of two different pathological processes. There was no evidence that cultural habits played any significant part in the aetiology of peripartum cardiac failure in The Gambia. PMID- 1597874 TI - Resistance to antituberculosis drugs in treated patients in Lagos, Nigeria. AB - The extent and pattern of drug resistance among previously treated tuberculosis patients was investigated. Ninety-six patients with a total treatment duration of between 6 and 18 months and still smear and culture positive were examined. Treatment was either continuous or in intermittent blocks. Drug susceptibility tests on strains of tubercle bacilli isolated from the patients were performed against isoniazid, streptomycin, p-aminosalicylic acid, ethambutol and rifampicin by the proportion method using LJ medium without potato starch. A total of 56% of the strains were resistant to one or more of the drugs tested. Resistance to isoniazid (38%) and streptomycin (29%) was most common. A significant finding in the study was the low level of resistance to rifampicin (2%) and ethambutol (3%). A relationship between the incidence of drug resistance and the nature and duration of previous treatment appeared likely since susceptible strains were isolated more often from patients with continuous treatment than from patients on intermittent blocks of long-course regimens. It is therefore suggested that the introduction of better supervision of drug taking and the adoption of continuous short-course regimens on a nationwide level will contribute immensely towards the reduction of the drug resistance problems in Nigeria as well as in other developing countries. PMID- 1597876 TI - Lassa fever encephalopathy: clinical and laboratory findings. AB - Clinical and laboratory findings are reported in nine patients who developed acute encephalopathy during the course of Lassa fever. The encephalopathy manifested 3-17 days after disease onset with confusion, followed rapidly by tremor (seven patients), grand mal convulsions (seven), abnormal posturing (three) and coma (eight); focal neurological signs and evidence of raised intracranial pressure were not seen. Eight patients died, most commonly from respiratory arrest following a protracted fit. Development of encephalopathy did not correlate with the presence of virus in cerebrospinal fluid (CSF), nor with virus antibodies in CSF and/or serum; thus, neither direct cytopathic nor immune mediated mechanisms seem to be involved in its pathogenesis. PMID- 1597877 TI - Haemagglutinating and buccal epithelial cell adherence activities of Vibrio parahaemolyticus: correlation with virulence. AB - Clinical and environmental isolates of Vibrio parahaemolyticus were examined for their ability to agglutinate human and rabbit erythrocyte and to adhere to human buccal epithelial (HBE) cells in the presence or absence of mannose. All strains produced cell-associated haemagglutinins (HGs) after 3 h at 37 degrees C. Mannose sensitive haemagglutination (MSHA) appeared to be a significant marker for differentiating between clinical and environmental isolates; 75% of clinical and 11% of environmental isolates exhibited MSHA with rabbit erythrocytes. All strains showed mannose-resistant adhesion (MRA) to HBE cells whose pattern had no relationship to the epidemiological source of the isolates. Adherence to HBE cells correlated with haemagglutination (HA) capability of environmental but not clinical isolates. This suggests that although intestinal adherence may be an essential step in vibrio colonization, it may not be a sufficient prerequisite for the subsequent expression of pathogenicity in Vibrio parahaemolyticus. PMID- 1597878 TI - Louse-borne relapsing fever in children. AB - Clinical manifestations of louse-borne relapsing fever (LBRF) in children admitted to Jimma Teaching Hospital from March 1991 to September 1991 are described. The clinical manifestations were mild and the frequency of occurrence of each feature was lower than in adults. Jaundice and cardiac abnormality have not been found in children. The Jarisch-Herxheimer reaction was also mild and occurred in about 16% of the cases. The prognosis of LBRF was excellent. Initial treatment with penicillin and continued treatment with tetracycline for a couple of days was justifiable. Further detailed studies with a larger series is recommended. PMID- 1597879 TI - Epidemiological aspects of Strongyloides stercoralis infection in Okinawa, Japan. AB - The epidemiology of Strongyloides stercoralis infection was compared among three localities with various prevalences of human T lymphotropic virus type 1 (HTLV-1) infection in Okinawa Prefecture, Japan, using agar-plate culture of faeces. The prevalence of S. stercoralis infection is much higher in Gusukube, where HTLV-1 infection is rare, than in Yomitan, where this viral infection is common. In all localities the parasite prevalence is significantly higher in males than in females, whereas the prevalence of HTLV-1 infection is much higher in females. These epidemiological facts suggest that infection by S. stercoralis occurs independently of that by HTLV-1. PMID- 1597880 TI - Wuchereria bancrofti microfilarial density of autochthonous cases and natural Culex infectivity rates in northeast Brazil. AB - Autochthonous Wuchereria bancrofti microfilaraemic cases from three neighbouring cities of Northeast Brazil (Recife, Jaboatao and Olinda) were selected from thick smear or filtration positive individuals and classified by their microfilarial (mf) densities through polycarbonate membrane blood filtration. Individuals were subdivided into two groups: autochthonous cases without any previous specific drug administrations (group A) and those with one or more previous DEC treatments (group B). In Recife, unlike Jaboatao and Olinda (P less than 0.05), the majority of autochthonous cases were over 20 years old and no microfilaraemics were found under the age of 10. The majority of cases in Recife had lower levels of mf density (66.6%), while in Jaboatao and Olinda higher mf carriers (65.6%) prevailed when group A (n = 141) individuals were rearranged in mf density above and below 500 mf ml-1 (P less than 0.01). All subjects in group B (n = 110) had less than 501 mf ml-1 and the great majority less than 100 mf ml-1, but a significant difference (P less than 0.05) between Recife and the two other cities was observed. Captured mosquitoes in Recife, Jaboatao and Olinda totalled 7856, 8010 and 8003 respectively. The infectivity rate found in Recife (0.61%) was significantly lower than in Jaboatao (1.21%) and Olinda (1.31%) (P less than 0.001). The authors discuss the possible influences of previous disease control programmes (medicated salt and individual treatments) applied only to the city of Recife in relation to the outcome of this investigation. PMID- 1597881 TI - Age distribution of diarrhoeal and healthy children infected with Campylobacter jejuni. AB - The prevalence of infection with Campylobacter jejuni in diarrhoeal and healthy children (age less than 7 years old) was investigated from 1 March to 31 May 1988 in Chengdu city, China. The isolation rate in diarrhoeal children (11.88%) was higher than in healthy children (4.62%) (P less than 0.005). In both diarrhoeal and healthy children, infants (less than 12 months of age) had lower rates of infection than older children (P less than 0.005 and P less than 0.05 respectively). The frequency of C. jejuni was lowest in diarrhoeal children aged less than 6 months, highest in those aged 12 to less than 24 months. The isolation rate in healthy children was also lowest in those aged less than 6 months, and no difference occurred among age groups of greater than 12 months. Our results show that the isolation rate in diarrhoeal children was rising with increasing age up to 12 months of age, tending to stabilize with increasing age after 12-24 months of age in Chengdu, China. PMID- 1597882 TI - Oral aluminium phosphide poisoning in Indian children. AB - Aluminium phosphide, due to its low cost, easy availability and highly toxic nature, is emerging as a common self-poisoning agent in adults. In children, besides accidental ingestion, it is usually given by their parents who themselves have taken it with suicidal intentions. Seven such cases in children are reported. Since prevention is the only logical approach there is an urgent need to take appropriate steps to prevent further loss of lives. PMID- 1597883 TI - Precoating expanded polytetrafluoroethylene grafts alters production of endothelial cell-derived thrombomodulators. AB - Although the use of extracellular matrix proteins to precoat small-caliber vascular grafts before endothelial cell seeding has been shown to improve cell attachment, proliferation, and adherence, the effect of precoating on the thrombomodulatory properties of the seeded cells is unknown. The use of vascular prostheses lined with confluent endothelial cell monolayers expressing optimal thromboresistant properties may enhance patency rates. In this study human saphenous vein endothelial cells were seeded onto expanded polytetrafluoroethylene (ePTFE) graft material, both unmodified and precoated with fibronectin, type I collagen, or fibronectin and type I collagen (fibronectin/type I collagen). After 3 days of in vitro cultivation, endothelial cell production of prostacyclin, tissue plasminogen activator, and plasminogen activator inhibitor was evaluated under basal conditions and after stimulation with arachidonate or thrombin. Production of tissue plasminogen activator by endothelial cells cultured on fibronectin-ePTFE was significantly greater compared with production by endothelial cells grown on noncoated or fibronectin/type I collagen-ePTFE under basal conditions (p values less than 0.01 and less than 0.05, respectively) and in response to thrombin (p values less than 0.002 and less than 0.003, respectively). Plasminogen activator inhibitor-1 production was not detected in any of the four experimental groups. Endothelial cells cultured on fibronectin-ePTFE also synthesized significantly more prostacyclin than endothelial cells grown on type I collagen- or fibronectin/type I collagen-ePTFE, under basal conditions (p values less than 0.02 and less than 0.01, respectively) and in response to arachidonate (p values less than 0.03 and less than 0.002, respectively) and thrombin (p values less than 0.003 and less than 0.002, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597884 TI - Arterial laser welding with a 1.9 micrometer Raman-shifted laser. AB - A new 1.9 micron Raman-shifted neodymium:yttrium aluminum garnet (Nd:YAG) laser was used for small vessel welding. Bursting pressures and stresses of sutured and laser-welded arteriotomies created in the rat femoral artery and aorta were measured. Sutured arteriotomies had a significantly higher burst stress than laser-welded arteriotomies. Although there were no significant differences in burst stress at the various laser powers tested, an optimal power was identified. The laser was also used to weld transected rat aortas. The average power delivered was 200 mW for 30 seconds per anastomosis. The average time for completing an anastomosis was 6 minutes compared with 18 minutes when sutures were used. In relation to proximal aortic diameter, there was a 7.9% decrease at the anastomosis immediately (n = 4), and a 6.6% and 4.9% increase occurred at 24 hours (n = 4) and 10 weeks (n = 5), respectively. Acute anastomotic compliance, and compliance at 24 hours and 10 weeks were decreased by 47.2%, 39.5%, and 47.8%, respectively, and were similar to sutured anastomoses. Histology showed little thermal denaturation of the aorta within 0.6 mm of the anastomosis, approximately 1 mm of medial cell death, and nearly normal elastic fiber alignment. One focal false aneurysm was noted at 10 weeks. Although the sutured and laser-welded anastomoses share similar compliance changes, the laser-welded anastomoses are more isodiametric. This preliminary experience with the 1.9 micron laser shows the distinct advantages of a handheld fiber, no requirement for cooling irrigation, speed, and no difference in compliance from sutured anastomoses. PMID- 1597885 TI - Late stroke after carotid endarterectomy: the role of recurrent stenosis. AB - Perioperative stroke after carotid endarterectomy has been well studied, although little information is available regarding later strokes. We determined the etiology of late stroke after carotid endarterectomy by examining the records of those patients in our carotid registry who had a stroke more than 30 days after surgery. Thirty-five (5.1%) of the 688 patients in our registry had a stroke more than 30 days after surgery (mean follow-up, 59.3 months; standard error, 1.8 months; range, 1 to 292 months). The cause of late stroke was established by input from consulting neurologists, CT scanning of the head, magnetic resonance imaging results, angiograms, noninvasive studies, and postmortem examinations. Eight of the 11 strokes of unknown origin were massive fatal events for which no further evaluation was undertaken. Restenosis or occlusion accounted for fewer strokes (3 of 20, 15%) in the 1- to 36-month postoperative interval than in the greater than 36-month interval (8 of 15, 53.7%) (p less than 0.02 by Fisher's Exact Test). These data support the hypothesis that the early pseudointimal hyperplastic lesion is less likely to result in stroke than is later recurrent stenosis, which is usually related to atherosclerosis. PMID- 1597886 TI - The current surgical management of carotid body paragangliomas. AB - To determine if recent trends in evaluation and therapy have contributed to the successful surgical management of carotid body paragangliomas, we reviewed our experience over the past decade. Nineteen carotid body paragangliomas were identified in 17 patients. Eleven patients underwent complete, preoperative embolization of their afferent arteries with one complication. Calculated carotid body paragangliomas surface areas did not differ between the embolized 64.6 +/- 43.3 cm2 and nonembolized 63.0 +/- 57.9 cm2 lesions. Intraoperative blood loss was lower (p = 0.02) in the patients treated with embolization (372 +/- 213 ml) compared with their cohorts (609 +/- 564 ml). However, the operative times were equivalent 4.1 hours versus 4.5 hours in both groups. Intraoperative electroencephalographic (EEG) monitoring was used in 10 patients; in one patient the EEG indicated intraoperative thrombosis of the carotid artery, which was successfully treated by thrombectomy without complications. Two patients required carotid bifurcation resection and vascular reconstruction to remove the entire tumor; a late stroke manifested by contralateral hand weakness developed in one of these patients. The incidence of cranial nerve injury was low at 16%, with one transient ramus mandibularis paresis and two instances of vocal cord dysfunction. Two additional patients had a postoperative Horner's syndrome. We conclude that by diminishing intraoperative blood loss through complete and careful preoperative embolization and use of intraoperative EEG monitoring along with careful surgical technique, the complications associated with this challenging operation are facilitated and diminished. PMID- 1597887 TI - Recommended indications for operative treatment of abdominal aortic aneurysms. Report of a subcommittee of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery. PMID- 1597888 TI - Exposure of femoral vessels by a suprainguinal incision. PMID- 1597889 TI - A simple technique to protect subcutaneous vein grafts. PMID- 1597890 TI - Intravascular ultrasonography: redefining vascular imaging with use of two dimensional and three-dimensional reconstructions. PMID- 1597892 TI - A venous renaissance? PMID- 1597891 TI - Venous duplex ultrasonography causing acute pulmonary embolism: a brief report. PMID- 1597893 TI - Axillofemoral bypass: outcome and hemodynamic results in high-risk patients. AB - Aortobifemoral bypass (AoFB) is the preferred method to provide lower extremity inflow. To determine whether axillofemoral bypass (AxFB) is an acceptable alternative for high-risk patients, we reviewed our results with these two operations. Between 1985 and 1990, 29 axillobifemoral and 5 axillounifemoral bypass procedures were performed preferentially because of severe associated medical illness in patients with severe aortoiliac occlusive disease. During the same interval, 107 patients received an AoFB for pure aortoiliac occlusive disease. Nearly all patients having AxFB and AoFB were heavy smokers, and the two groups had similar rates of hypertension and angina. However, other major risk factors were more frequently found in patients undergoing AxFB. Limb-threatening ischemia was more frequent and femoral artery occlusive disease was more severe in patients having AxFB. Anastomosis to the deep femoral arteries and concomitant infrainguinal bypass were more likely to be required in patients who had AxFB. Life-table patient survival at 3 years was 35% for AxFB versus 91% for AoFB (p less than 0.001). Primary patency at 3 years was 63% for AxFB versus 85% for AoFB (p = 0.032). Secondary patency was 74% for AxFB versus 94% for AoFB (p less than 0.001). However, all revised grafts in both groups were patent at 36 months, and only one revised AxFB graft was an ultimate failure. Limb salvage at 3 years was 76% for AxFB versus 97% for AoFB (p = 0.065). Nineteen of the 22 patients with AxFB who died during follow-up died with patent grafts. Hemodynamic performance of AxFB and AoFB were compared. Mean preoperative ankle-brachial index was higher in AoFB (0.50) than AxFB (0.38, p less than 0.001), but postoperative ankle brachial index was much higher after AoFB (0.83) than AxFB (0.57, p less than 0.001). Even after adjustment for severity of outflow disease, postoperative ankle-brachial index was much better after AoFB than AxFB. Axillofemoral bypass was performed in older higher risk patients with more severe ischemia than those in the AoFB group. Hemodynamic performance was inferior and graft failure more common after AxFB. However, AxFB provided limb salvage in all but 2 of 22 patients who have died, and no survivor has had amputation because of graft failure. Axillofemoral bypass is an acceptable but hemodynamically inferior alternative to AoFB in properly selected high-risk patients with critical lower extremity ischemia who would likely not tolerate the more durable AoFB. PMID- 1597894 TI - Does the clinical evaluation of the cardiac status predict outcome in patients with abdominal aortic aneurysms? AB - A cost-effective method to reduce mortality rates after abdominal aortic aneurysm repair centers on selecting and investigating only those patients at risk for cardiac-related death. All 146 patients undergoing asymptomatic abdominal aortic aneurysm repair over a 5-year period (1986 to 1990) were retrospectively placed into one of the three following groups on the basis of a clinical evaluation. Group I: no history of myocardial infarction or angina, no congestive heart failure, and no ischemic changes on electrocardiogram (ECG). Group II: history of myocardial infarction or class I-II angina or ischemic changes on ECG. Group III: presence of congestive heart failure or class III-IV angina. Patients in group I had no further cardiac work-up; patients in group II with angina had left ventricular ejection fraction assessment by multiple gated acquisition (all greater than 37%) and were cleared for operation by a cardiologist; patients in group II without angina had no further cardiac work-up; patients in group III had coronary angiography and then coronary revascularization. The overall mortality rate was 4.8%, with a cardiac mortality rate of 3.4%. The mortality rate in group I (n = 64) was 1.8%, with no cardiac-related deaths; the mortality rate in group II (n = 63) was 9.5% (8% cardiac-related deaths). No deaths occurred in group III (n = 19). The difference between the cardiac mortality rates in groups I and II was significant (p = 0.02) as was the postoperative cardiac morbidity: total myocardial infarctions (p less than 0.001); congestive heart failure (p = 0.02); tachyarrhythmias (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597895 TI - Dipyridamole-thallium scintigraphy predicts perioperative and long-term survival after major vascular surgery. AB - The purpose of this study was to evaluate the ability of dipyridamole-thallium scintigraphy to predict perioperative and late cardiac events after peripheral vascular operations. A total of 262 patients had dipyridamole-thallium scintigraphy before 87 infrainguinal reconstructions, 108 abdominal aortic aneurysm operations, and 67 aortobifemoral bypass grafts that were placed for occlusive disease. Follow-up extended to 5 years (mean, 31.1 months). Logistic regression analysis selected dipyridamole-thallium scintigraphy redistribution as the best predictor of perioperative events. Fixed defects were not predictive. A Cox proportional hazards model for a variety of clinical risk factors and scan parameters identified fixed defects and a history of congestive heart failure as the strongest predictors of late cardiac events. The presence of greater than 1 or 2 fixed segments were the best predictors in patients with an abnormal scan; redistribution did not predict late events. The risk of combined perioperative or late cardiac events was 29% for infrainguinal, 19% for abdominal aortic aneurysm, and 7.5% for aortobifemoral operations. Life-table analysis showed that after a cluster of perioperative events that occurred primarily in patients with dipyridamole-thallium scintigraphy redistribution, most of the late cardiac morbidity and deaths occurred in patients with fixed defects. PMID- 1597896 TI - Safety of vein bypass grafting to the dorsal pedal artery in diabetic patients with foot infections. AB - The results of 56 vein bypasses to the dorsal pedal artery performed in 53 diabetic patients who were admitted with ischemic foot lesions complicated by infection were reviewed. All patients had one or more of the following: infected ulcers (73%), cellulitis (45%), osteomyelitis (29%), gangrene (20%), or abscess (2%). Organisms were cultured from 84% of patients (average 2.6, range 1 to 9 organisms per infection). Elevated temperature (greater than 37.7 degrees C) or leukocytosis (greater than 9.0 x 10(3)/ml) were seen in 13% and 50% of patients, respectively. All patients were treated with broad-spectrum antibiotics, local debridement, wound care, and bed rest. Operative debridement or open partial forefoot amputation were required to control sepsis in 11 patients (20%). Treatment of infection delayed revascularization by an average of 10.7 days. All patients underwent autogenous vein bypasses to the dorsal pedal artery. Two grafts failed within 30 days (3.6%), and one patient died (1.8%). Wound infections developed in seven patients (12.5). One wound infection resulted in graft disruption and patient death at 2 months. Average length of stay of the initial hospitalization was 29.8 days. Fifty-two patients were discharged with patent grafts and salvaged limbs; however, 31 subsequent foot procedures and 35 rehospitalizations were required to ultimately achieve foot healing. Actuarial graft patency and limb salvage were 92% and 98%, respectively at 36 months. Pedal bypass to the ischemic infected foot is efficacious and safe as long as infection is adequately controlled first. The complexity of these situations often requires multiple surgical procedures and extensive wound care, resulting in prolonged or multiple hospitalizations. PMID- 1597897 TI - The variation in vein graft flow velocity with luminal diameter and outflow level. AB - Duplex scanning has recently been used to monitor the patency of infrainguinal vein grafts. Empirically derived criteria that have been used for identifying the failing graft have never accounted for the effect of vein graft diameter or varying outflow resistance, despite the fact that they are major determinants of flow. We prospectively examined the variation in graft peak systolic flow velocity with graft diameter and outflow level in a consecutive series of 68 patients with 72 normally functioning vein grafts returning for routine follow up. Images were obtained of vein grafts with a duplex scanner throughout their lengths, and the distal peak systolic flow velocity and intraluminal diameters were recorded. There were 15 popliteal, 26 tibial, and 21 inframalleolar grafts. The mean ankle-brachial index of inframalleolar grafts was 1.01 +/- 0.04 and did not differ significantly from tibial (0.96 +/- 0.03) or popliteal (0.93 +/- 0.06) grafts (p = 0.32). Grafts to the three outflow levels differed significantly in diameter, with inframalleolar grafts measuring 3.95 +/- 0.17 mm, tibial grafts 4.78 +/- 0.21 mm, and popliteal grafts 5.65 +/- 0.38 mm (p = 0.0001). In a similar manner inframalleolar grafts had significantly lower peak systolic flow velocities (59.1 +/- 3.4 cm/sec) than tibial (77.2 +/- 5.6 cm/sec) or popliteal (71.0 +/- 7.6 cm/sec) grafts (p = 0.04). Inframalleolar grafts did not demonstrate a significant correlation (r = -0.21, p = 0.29) between peak systolic flow velocity and graft diameter. Conversely, both tibial (r = -0.49, p = 0.005) and popliteal (r = -0.73, p = 0.002) grafts demonstrated significant inverse correlations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597898 TI - US Government criticized for helping to export a deadly epidemic of tobacco addiction. PMID- 1597899 TI - Margaret A. Winker, MD, comes to JAMA as 12th Fishbein Fellow in Medical Journalism. PMID- 1597900 TI - From the Food and Drug Administration. PMID- 1597901 TI - From the Centers for Disease Control. Outbreak of Salmonella enteritidis infection associated with consumption of raw shell eggs. PMID- 1597902 TI - From the Centers for Disease Control. Fluoridation of community water systems. PMID- 1597903 TI - Tobacco: promotion and smoking. PMID- 1597904 TI - Tobacco: promotion and smoking. PMID- 1597905 TI - Environmental tobacco smoke and heart disease. PMID- 1597907 TI - Mexico! It's Marlboro country. PMID- 1597906 TI - Environmental tobacco smoke and heart disease. PMID- 1597908 TI - No-smoking policies in hospitals. PMID- 1597909 TI - Treatment decisions about cholesterol: what about smoking? PMID- 1597910 TI - Low-dose amiodarone for maintenance of sinus rhythm after cardioversion of atrial fibrillation or flutter. AB - OBJECTIVE: To study efficacy and safety of low-dose amiodarone for maintenance of sinus rhythm after electrical cardioversion of atrial fibrillation or flutter. DESIGN: Nonrandomized trial; mean duration of follow-up, 20.7 months. SETTING: Referral center; institutional practice; both hospitalized and ambulatory care. PATIENTS: Eighty-nine consecutive patients having chronic atrial fibrillation or flutter and eligible for cardioversion. Patients had failed previous treatment aimed at maintaining sinus rhythm. During follow-up one patient was withdrawn because of side effects; all patients were available for follow-up. INTERVENTION: Before cardioversion, patients received 600 mg of amiodarone daily during a 4 week loading period. After conversion, the daily maintenance dose was 204 +/- 66 mg (mean +/- SD). MAIN OUTCOME MEASURES: Arrhythmia recurrence and adverse effects causing drug discontinuation. RESULTS: During loading, 15 patients (16%) converted, and after electrical cardioconversion, 90% of all patients had sinus rhythm. Actuarially, 53% of these patients were still in sinus rhythm after 3 years. In patients with compromised left ventricular function, 93% maintained sinus rhythm after 6 months. One patient died due to congestive heart failure. Intolerable side effects occurred in one patient. No proarrhythmia was observed. Logistic regression analysis revealed that amiodarone was ineffective in patients with mitral stenosis or chronic arrhythmia. CONCLUSIONS: Low-dose amiodarone is effective for maintaining sinus rhythm in patients with difficult to treat chronic atrial fibrillation or flutter and is associated with a low incidence of serious side effects. PMID- 1597911 TI - Does capitation affect the health of the chronically mentally ill? Results from a randomized trial. AB - OBJECTIVE: To determine the effect on health outcomes of enrollment of chronically mentally ill Medicaid recipients in prepaid plans vs traditional fee for-service Medicaid. DESIGN: A randomized controlled trial. Clients who were randomly assigned to prepaid care were then permitted to choose among four capitated health plans. Clients returned to fee-for-service care at the end of the demonstration. SETTING: The Medicaid Demonstration Project in Hennepin County, Minnesota, the urban center of which is Minneapolis. PATIENTS: Seven hundred thirty-nine Medicaid clients who were classified as having chronic mental illness on the basis of Medicaid claims. Clients were interviewed at baseline (time 1) and at two follow-up points. Data were available for 96% of participants at the end of the intervention (time 2). Average duration of follow-up was 11 months. A subset of 370 clients with schizophrenia was followed up 11 months after the return of the prepaid group to fee-for-service care (time 3). MAIN OUTCOME MEASURES: General health status, physical functioning, social functioning, and psychiatric symptoms, assessed using the Schedule of Affective Disorders and Schizophrenia-Change version, the Global Assessment Scale, and indicators of community function. RESULTS: No significant differences between prepaid and fee-for-service groups in general health or psychiatric symptoms from baseline to time 2. After regression adjustment, 12% fewer clients in the prepaid group reported being victimized (P less than .01). At the end of time 3, the regression-adjusted Global Assessment Scale scores had worsened by 7.6 points more in the prepaid group in comparison with the fee-for-service group (P less than .02). CONCLUSION: There was no consistent evidence of harmful effects of enrolling chronically mentally ill Medicaid clients in prepaid care, at least in the short run. The generalizability of these findings may be limited to plans that control utilization by methods similar to those used in this study setting. Longer-term outcome studies should be undertaken to clarify the strength of the findings. PMID- 1597913 TI - An annotated algorithm approach to clinical guideline development. AB - The Urinary Incontinence in Adults Guideline Panel facilitated the ready elucidation of its guideline's management recommendations through the use of an annotated algorithm approach. The algorithms created as part of this guideline differ from previous algorithms in two ways: (1) they employ systematic annotation to link explicitly the algorithms' recommendations to the literature, and (2) they contain patient counseling and decision nodes to depict the major preference-dependent decision or branch points in the algorithm. We believe that these two innovations can help ensure the clinical validity of guidelines' algorithms while preserving appropriate clinical flexibility and respecting patient preferences. PMID- 1597912 TI - Risk of subsequent basal cell carcinoma and squamous cell carcinoma of the skin among patients with prior skin cancer. Skin Cancer Prevention Study Group. AB - OBJECTIVE: The primary aims of this study were to assess risk of subsequent basal and squamous cell skin cancer among patients with a prior history of these tumors and to examine these risks in relation to patient characteristics and life-style factors. DESIGN: Follow-up of participants in a randomized trial of betacarotene as a possible skin cancer preventive agent. SETTING: Clinical centers in Los Angeles, Calif, San Francisco, Calif, Minneapolis, Minn, and Hanover, NH. PARTICIPANTS: Patients (n = 1805) who were diagnosed as having a basal or squamous cell skin cancer between January 1980 and February 1986 and were free of skin cancer at study entry. MAIN OUTCOME MEASURE: Time from study entry to first new occurrence of basal and squamous cell skin cancer. RESULTS: The estimated risk of developing one or more new skin cancers was 35% at 3 years and 50% at 5 years. New skin cancers tended to be of the same cell type as the previous skin cancers. For both basal and squamous cell skin cancer, risk was higher among patients who were male, were over the age of 60 years, had more prior skin cancers, had severe actinic skin damage, or who burned easily with sun exposure. Compared with those who had never smoked, the rate of subsequent squamous cell skin cancer was higher among current smokers (rate ratio, 2.01; 95% confidence interval, 1.21 to 3.34) and former smokers (rate ratio, 1.62; 95% confidence interval, 1.07 to 2.47) and increased with both duration and amount smoked. There was no clear relationship between smoking and basal cell skin cancer; the rate appeared lower among heavy smokers but was unrelated to duration of smoking. CONCLUSIONS: Persons with a prior nonmelanoma skin cancer had a substantial 5 year risk of developing another tumor of the same histologic type. Number of previous skin cancers, solar damage, and skin sensitivity to sun exposure were particularly related to this risk. The increased risk of squamous cell skin cancer associated with cigarette smoking merits further study. PMID- 1597914 TI - Intravenous immunoglobulin therapy for toxic shock syndrome. AB - Staphylococcus aureus and group A Streptococcus pyogenes produce toxic shock syndrome characterized by hypotension and multisystem organ failure. While conventional therapy has consisted of antibiotics and intensive supportive care, some experimental evidence suggests that immunoglobulins directed against the toxins may be effective additional therapy. We report a case of "toxic strep syndrome" in which intravenous immunoglobulin was administered when signs and symptoms were worsening while the patient was receiving conventional therapy. Within hours of administration of the intravenous immunoglobulin, the patient experienced dramatic clinical improvement. This response suggests a possible therapeutic benefit of intravenous immunoglobulin in toxic shock syndrome. PMID- 1597915 TI - Ten years of orienting college students to careers in medicine. PMID- 1597916 TI - Evolving strategies for the management of atrial fibrillation. The role of amiodarone. PMID- 1597917 TI - Recycling and recycled paper. PMID- 1597918 TI - Clinical decision making: from theory to practice. Cost-effectiveness analysis. Is it up to the task? PMID- 1597919 TI - Ataxia-telangiectasia in children. PMID- 1597920 TI - Behcet's disease. PMID- 1597921 TI - Bismuth an old drug with new therapeutic implications. PMID- 1597922 TI - Acute lymphoblastic leukaemia--a study of immunophenotypes. AB - Immunological characteristics of leukaemic blast cells from 55 patients of acute lymphoblastic leukaemia were analysed using a panel of monoclonal antibodies and immunoperoxidase technique. Among 36 children the percentage of Common-ALL was found to be low (39%) as compared to western reports, whereas that of T-ALL was high (36%). Out of 19 adults, 52.6% were Common-ALL, 21.1% Early-B-ALL and 16% T ALL; the findings being consistent with western studies. The T-ALL cases (13) were subclassified according to the stage of thymic maturation depending upon the expression of CD8 and CD4 antigens. Six were identified as early, 3 as common and 4 as late thymocyte stage. PMID- 1597923 TI - Platelets and leucocyte counts in pregnancy. AB - A study involving the obstetric clinic population of 3 major teaching hospitals of Karachi has been conducted to define changes in leucocyte and platelet counts as pregnancy progresses. 573 "normal" pregnant women--183 in the first trimester, 195 in the second trimester and 194 in the third trimester were included in this analysis. We have found leucocytosis to be a feature of normal pregnancy; the change is subsequent to a progressive increase in granulocytes. Platelet counts were found to decrease slightly as pregnancy progresses. PMID- 1597924 TI - Ventricular CSF immunoglobulins in brain tumours. AB - Ventricular CSF glucose, total protein, protein electrophoresis, IgG, IgA, IgM and CSF cytology were determined in thirty seven patients with brain tumours. CSF glucose was unchanged and total protein was significantly high. Protein electrophoresis showed higher albumin and gamma globulin fractions. Mean IgG and IgA were significantly higher (P less than 0.001) in malignant tumours than in benign ones. IgM was detectable in 7 of 37 cases. The higher concentration of total protein, albumin and gamma globulin shows some degree of impairment of blood brain barrier. Increased concentration of IgG, IgA and IgM indicates humoral immune response of the brain against the tumours. PMID- 1597925 TI - Age related changes in the rat adrenal cortex. AB - The present study revealed that the growth of the rat adrenal gland was relatively slower than general body growth. However, growth of the cortex preceded that of the medulla. The parenchyma showed three usual zones but a fourth inconstant lipid-poor, zona intermedia between outer glomerulosa and middle fasciculata was also observed. In all cortical zones, the predominance of dark cells over the light cells occurred irrespective of the age groups studied. The advancing age replaced capsular cellular elements with fibrous ones whereas the mitotic activity of the parenchymal cells decreased and an increase in the intracellular lipid in the outer and ascorbic acid in the inner cortex was observed. The glycogen which was restricted mainly to the inner cortex remained unaffected by aging process while the acid phosphatase activity from the inner reticularis extended to the outer cortex in aged group. PMID- 1597926 TI - Economy and quality assessment of home made clinical chemistry reagents. AB - Most laboratories in Pakistan use expensive imported clinical chemistry reagent kits resulting in high cost/test to the patients. To reduce these costs, reagents were prepared from basic chemicals, substrates and enzymes imported from Sigma Chemical Company U.K. This reduced the cost/test by up to 500% in some reagents. The quality of these reagents was tested by Wellcome External, Q.C. Locally prepared reagents were comparable to or better than commercial reagents systems in terms of accuracy and precision. This paper describes the preparations according to I.F.C.C., costs and quality control of some of the reagents i.e., glucose, calcium, bilirubin, albumin, total protein, urea, ALT, AST and LDH and their comparisons with equivalent commercial kits. PMID- 1597928 TI - [Regional meetings of the Japanese Circulation Society, 1989. Abstracts]. PMID- 1597927 TI - Methotrexate as an alternative to surgery in ectopic pregnancy: a new role for an old drug. PMID- 1597931 TI - [The effect of ethanol on the metabolism of methamphetamine]. AB - In order to clarify the effects of ethanol (EtOH) on metabolism of methamphetamine hydrochloride (MA-HCl), the plasma and urine samples were taken from three groups of three male crab-eating monkeys (Macaca fascicularis). MA-HCl was given to the first group, both MA-HCl and EtOH were given once to the second group, the after consecutive administration of EtOH for four weeks, both MA-HCl and EtOH were given to the third group. Comparisons were made of the sequential change in the concentration of unchanged methamphetamine (MA) and its supposed metabolites, amphetamine (AP), p-hydroxymethamphetamine (p-HOMA), and p hydroxyamphetamine (p-HOAP). Additional hematological and plasma-biochemical tests were performed to monitor the influences under the administration of MA-HCl and EtOH on the animals. For the extraction of MA and its metabolites from blood and urine, a solid phase extraction was carried out with which an excellent recovery was achieved. Gas chromatography mass spectrometry (GC-MS) was used to measure the metabolites after changing them to the form of TFA derivative, producing good results. EtOH concentration in the blood was measured by GC using a head-space method. The biological half-life (t1/2) of MA tended to be shortened slightly in the plasma when EtOH was given consecutively. The maximum concentration of AP obtained by administration of EtOH was half that obtained by single administration of MA-HCl and the detectable time was shortened. A high concentration of p-hydroxy metabolites that the been almost undetectable when both MA-HCl and EtOH were administered once, was detected when EtOH was administered consecutively, compared with that when only MA-HCl was administered. Particularly, considerable amounts of p-HOAP was detected even after 72 hours. The trends seen in the excretion of MA and its metabolites into the urine were the same as seen in their plasma concentrations, although there was a difference in the detectable time. The urine collected in a metabolic cage for the monkey was contaminated with drinking water, so that the total amounts of metabolites, rather than sequential change as in the case of plasma, were considered to be of greater significance. When EtOH was administered consecutively, the excreted amounts of p-HOAP in the urine increased saliently and characteristically.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597929 TI - Dinucleotide repeat polymorphism at the apolipoprotein AII locus--phenotyping from peripheral blood and hair. AB - The genomes of eukaryotes including humans contain very short simple sequence repeats such as (dA-dC)n and (dG-dT)n. Recently, these repeats have been reported to exhibit marked length polymorphism due to wide variation in their reiteration numbers. We report here dinucleotide repeat polymorphism at the apolipoprotein AII locus in Japanese subjects. The informativeness in Japanese was as high as in Caucasians (PIC value and heterozygosity of 0.67 and 0.72, respectively), but their allele frequencies were different with statistical significance. We also discuss the advantages of using dinucleotide repeat polymorphisms in forensic science, demonstrating determination of phenotype from not only a single hair root but also a short hair shaft. PMID- 1597930 TI - [Experimental studies on the efficacy of PAM against sumithion poisoning]. AB - The efficacy of 2-Pyridine aldoximide methiodide (PAM) for lethal acute poisoning by fenitrothion (FNT) was investigated in mice and dogs. Sumithion (FNT 51.7%, emulsifiers 12.5% and xylol 35.8%) was used as fenitrothion. 1. FNT at 1500 mg/kg was administered orally to mice. After ten minutes 50 mg/kg of PAM was injected once iv, and plasma, erythrocyte, brain, liver and kidney ChE activities were investigated 30 and 60 min later. Recovery in ChE activity was found in every organ but the brain at 30 min, but no efficacy of PAM was observed at 60 min. 2. After administering 1500 mg/kg of FNT orally to mice, the life-saving effect was studied from the changes in mortality due to variation of PAM route, dosage and number of administrations. With oral administration of 1500 mg/kg of FNT, 75 to 85% of the animals died. The mortality ranged from 80 to 95% when the animals received a single intravenous injection of 50 mg/kg of PAM between zero and 60 min following the FNT administration. Thus, a single intravenous administration of PAM at 50 mg/kg showed no life-saving effect on the animals given FNT. However, the mortality was reduced to 45% when the animals received repeated subcutaneous injections of 20 mg/kg of PAM at a 3-hr interval from just after administration of FNT over 24-hr. In other repeated subcutaneous injection experiments, the mortality ranged from about 55 to 65%. In any PAM-treated group, the survival time was prolonged. This life-prolonging effect was more marked in the case of repeated subcutaneous injections of PAM by 12-hr and even more by 24 hr, than in the case of a single intravenous injection. FNT treatment caused marked salivation and watery diarrhea, and PAM clearly inhibited these signs of the muscarinic action of FNT. There was a high relationship between this inhibitory effect of PAM on the muscarinic action and its life-prolonging or life saving effect. 3. PAM (150 mg/animal/shot, iv) was given 12 or 13 times during 7 hr from 10 min (4 animals), 3 hr (1 animal) and 6 hr (2 animals) after administration of FNT at 150 mg/kg. The effects of PAM on survival, plasma ChE activity, plasma protein (TP) and hematocrit (Ht) values were examined. The 3 dogs given FNT alone all died within 53 hr of administration, whereas 6 out of 7 animals treated with PAM survived.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597932 TI - [Comparison of fingerprints using a personal computer and graphic software sold on market]. AB - We compared the fingerprint images using a personal computer and a graphic software sold on market. The fingerprints of thumb of left hand recorded by pressing and rolling on paper were input in computer using image scanner. These two fingerprint images were overlapped by moving and rotation on the computer screen, and were fitted well. This result showed that the fingerprints recorded by any way from one person were fitted. Latent and accused's fingerprints were also input in computer using image scanner. These images were analyzed by the same procedure. These two fingerprints were part by unfitting. It was decided these two fingerprints were not derived from one person. We also considered the possibility that the latent fingerprint was the reversed one. Then, the image was reversed of its color on the screen of computer (black to white and white to black) and compared by the same procedure. In this experiment, two fingerprint images were not fitted in a part. This showed that the reversed fingerprint was also able to be analyzed by this procedure. For the comparison of fingerprints, this report showed the ability of the personal computer and software which can be obtained easily from market. Following the improvement of the hardware and software used in this examination in near future, the computerized identification of fingerprints like this study will become more accurate and convenient. PMID- 1597933 TI - Comparison of EEG between nasopharyngeal and scalp leads with the aid of an automatic EEG analysis system. AB - We analyzed the EEG quantitatively with an automatic EEG analysis system, and introduced this system for investigation the relationship between the scalp EEG and nasopharyngeal EEG. The EEG was recorded from healthy volunteers by photic stimulation. We found that components of slow waves like delta and theta were more rich but alpha component was less in the nasopharyngeal EEG than in the scalp EEG. In the analysis of the rate of the appearance of each EEG wave using photic stimulus, a decrease of alpha 1 and an increase of theta 1 are observed in the scalp EEG while there are no specific changes of them in the nasopharyngeal and scalp EEGs. The nasopharyngeal EEG obtained from the vicinity of the base of the brain was thought to originate from the vicinity of the brain stem. PMID- 1597938 TI - [A case of coexistent bronchogenic carcinoma with pulmonary tuberculosis]. AB - A 79-year-old housewife complaining of shortness of breath presented with a LUL mass lesion on chest roentgenogram. Bronchofiberscopic biopsy and curettage revealed adenocarcinoma as well as acid-fast bacilli of Gaffky-4. Further investigations showed increased ESR, CRP levels and positive RF. PPD skin test was positive measuring 55 x 43 mm. A left upper lobectomy with mediastinal lymph node dissection was performed. The mass was in S1+2 and measured 2.7 x 2.5 x 1.5 cm. Histologically caseaous necroses and spotted granulomas of tuberculosis were surrounded by bronchioloalveolar cell carcinoma. Recent discussion concerning the simultaneous occurrence of pulmonary tuberculosis and bronchogenic carcinoma suggests a higher coexistence of both diseases. However, the coexistence of active tuberculosis with carcinoma in the same region, as in our case, is quite rare and suggests an etiological closer relationship between both diseases. PMID- 1597936 TI - [CT findings of six cases with intracranial tuberculosis in National Higashi Saitama Hospital]. AB - We have experienced 6 cases of intracranial tuberculosis since 1985. 2 cases were diagnosed as intracranial tuberculoma without tuberculous meningitis, and 4 cases were diagnosed as tuberculous meningitis. Brain CT showed intracranial tuberculomas in three of them, and showed cerebral infarcts in two cases, and showed hydrocephalus in two cases. Brain CT on intracranial tuberculosis showed various findings. In two cases with tuberculous meningitis, brain CT showed many tuberculomas with ringed or nodular enhancement appeared after adequate chemotherapy had been started. About 1 year later, a few tuberculomas were found with homogeneous enhancement and were enlarged while the chemotherapy was continued. But later they were reduced in size. The above facts may suggest that intracranial tuberculoma could appear and be enlarged on cranial CT in spite of adequate anti-tuberculous chemotherapy during a course of tuberculous meningitis. They also suggest that the continuation of adequate chemotherapy might be necessary to the treatment of intracranial tuberculomas. PMID- 1597937 TI - [Flow cytometric analysis of peripheral T lymphocytes from patients with mycobacterial diseases]. AB - Flow cytometric analysis was carried out on peripheral blood cells from patients with tuberculosis (TB) (n = 84) and with mycobacteriosis other than tuberculosis (MOTT) (n = 38). A whole blood-staining-hemolysis procedure was used for the preparation of samples being analyzed, and the cells were double-stained with various combinations of fluorescein isothiocyanate (FITC)- and phycoerythrin (PE) labeled monoclonal antibodies. These procedures enabled us to obtain quite reproducible results. As patients of more than 70 years old showed apparently distinct T lymphocyte profiles compared with those less than 70 years of age, this investigation was carried out only on patients of less than 70 years old. 1) The proportion of total lymphocytes to total leukocytes was significantly low in TB- and MOTT- groups, when compared with that in the healthy control group, although the total peripheral leukocyte number was not significantly different from each other. Thus, absolute numbers of lymphocytes were decreased significantly in TB- and MOTT- patients. 2) The numbers of both T and B lymphocytes in peripheral blood decreased in patients of both groups, leaving the ratio of T/B relatively constant. 3) Both CD4+/CD8- and CD4-/CD8+ subsets of T lymphocytes decreased in TB- as well as MOTT- groups. However, the decrease in CD4+/CD8- subset was more manifest than that in CD4-/CD8+ subset. Among CD4+/CD8- subset the proportion of the Leu8+ subpopulation was slightly lower and among CD4 /CD8+ subset CD11b- subpopulation was slightly higher in both TB- and MOTT- groups than in healthy control group. 4) There was no significant difference in proportions of IL-2-receptor (p55 alpha chain) positive as well as HLA-DR positive T-lymphocytes between patient groups and healthy control group. 5) Both TB- and MOTT- groups were subdivided according to the extent of pulmonary lesion. Patients with the larger lesion showed remarkable decreases in the ratio of T lymphocytes to total peripheral leukocytes, the number of T lymphocytes, and the numbers of CD4+/CD8- and CD4-/CD8+ subsets, when compared with those with the smaller lesion. 6) Although the averages of absolute numbers of T lymphocytes, CD4+/CD8- and CD4-/CD8+ subsets were lower in patient groups than in the control group and the ratios of these to total lymphocyte counts and the ratio of CD4+ to CD8+ subsets were not significantly different between patient groups and control group, the distributions of each value of individual person were far broad in patient groups.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1597940 TI - [Life with heart. Collage therapy]. PMID- 1597939 TI - [Postoperative surveillance and care of patients following heart surgery]. PMID- 1597934 TI - [Surgical treatment of pulmonary aspergilloma--with modified conservative operation]. AB - During the past 10 years 26 patients were operated on for pulmonary aspergilloma (20 males and six females, mean age of 55.8 years). Lung resections were performed on 13 cases (Group 1). Conservative operations were performed on the remaining cases, including one bilateral operation case (Group 2). New paragraph. The operative techniques in Group 1 were: lobectomy 11 cases of lobectomy, one case of partial resection; and one case of segmental resection. The operative techniques for Group 2 were; five cases of thoracoplasty and cavernoplasty; three cases of thoracoplasty plus cavernoplasty and muscle flap; three cases of thoracoplasty and muscle flap; one case of thoracoplasty and air-plombage; and two cases of cavernoplasty. A second operation was required in four and seven cases in Groups 1 and 2, respectively, and a third operation in two and four cases respectively. The conservative technique was used in all of additional operations required. The mean operation time and amount of blood loss were 262 min and 1,943 ml for Group 1 and 170 min and 918 ml for Group 2-being shorter and lesser for Group 2. Both the operation time and blood loss were reduced during the second and third operations. Reduction of %VC after the first operation was also less remarkable for Group 2 (-9.6%, No = 9). The advantage of using a conservative technique is that successful results can be expected without insult to the hilus and mediastinal surface in cases with compromised pulmonary functions, or in those cases which pneumonectomy or resection is difficult because of the risk of massive bleeding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1597943 TI - [Nursing in an interview with Hilde Steppe]. PMID- 1597935 TI - [Investigation of the cases due to Mycobacterium kansasii in our hospital]. AB - A clinical study of 23 patients with Mycobacterium kansasii infection of the lung encountered at National Chiba Higashi Hospital from 1988 to 1990 was carried out. All 23 cases were male, aged from 25 to 81 years-old. Diagnoses were confirmed by sputum culture. The cases consisted of 15 primary infections and 8 secondary infections. Out of the 23 cases, 11 were detected by mass screening with chest X ray findings, 10 cases were discovered when visiting the hospital because of chest complications and two cases were diagnosed during the observation of other diseases. On admission, sputum smear examinations were positive for 15 patients and negative for 8 patients. Chest X-ray findings using the roentgenological classification criterion for pulmonary tuberculosis established by the Japanese Society for Tuberculosis, 20 cases revealed a Type II shadow and three cases revealed a Type III shadow. One patient has died from another disease, two are undergoing chemotherapy, two have ceased chemotherapy treatment, and 18 patients have completed the treatment, Sputum cultures rapidly turned to negative for mycobacterium detection after chemotherapy treatment. The prognosis is considered to be quite good. PMID- 1597945 TI - [The Federal Labor Court explained what is a pause]. PMID- 1597944 TI - [The Berlin Senate terminates academic nursing education]. PMID- 1597941 TI - [Environmental hygiene in nursing education? II]. PMID- 1597942 TI - [The Munich office of the German Nursing Association]. PMID- 1597947 TI - [For discussion: holistic nursing--daily life on the ward. An irreconcilable antithesis?]. PMID- 1597950 TI - [Aging well in an aging world. Questions and answers]. PMID- 1597949 TI - [Aging well]. PMID- 1597952 TI - [International meeting of the aged. "We want to be taken serious"]. PMID- 1597957 TI - [The Swiss Nursing Association's recommendations for voting: against the abusive use of reproduction techniques and genetic manipulation]. PMID- 1597951 TI - [The nursing process in geriatrics. Chance or risk?]. PMID- 1597953 TI - [Loving life passionately]. PMID- 1597955 TI - [New directions in education for the nursing professions. What is the Swiss Nursing Association doing?]. PMID- 1597954 TI - [On the trail of research, knowledge and practice. A safari in pediatrics]. PMID- 1597956 TI - [Position of the Swiss Nursing Association concerning the report "extra-hospital care as seen by the social insurance companies." Adopting a positive attitude]. PMID- 1597959 TI - [ +Nomen est omen]. PMID- 1597948 TI - [Trainees for nursing and hospital professions in Zurich: 1991 a few more students, but...]. PMID- 1597958 TI - [Life in a group. A party to the working conditions. Working with others, a daily reality, not always simple to live with. Short considerations on this point]. PMID- 1597960 TI - [A study on patients waiting for their diagnosis. The tortures of uncertainty]. PMID- 1597946 TI - [Catalog of activities for emergency nursing personnel. Work group Emergencies of the state federation of the German Nursing Society in Baden-Wurttenberg]. PMID- 1597962 TI - [Nursing diagnosis--the other view]. PMID- 1597964 TI - [To age and be well. May 12., the international day of Nursing]. PMID- 1597963 TI - [New directions for nursing education. How does the Swiss Nursing Association react?]. PMID- 1597961 TI - [Alternative nursing possibilities for patients with AIDS]. PMID- 1597965 TI - [Position of the Swiss Nursing Association to the report on "Home nursing from the viewpoint of the social insurances". Formulate the aims positively]. PMID- 1597966 TI - [Voting recommendations of the Swiss Nursing Association: against human procreation and gene technology]. PMID- 1597967 TI - [My place of work. Time for dialogue]. PMID- 1597968 TI - Fenestrated Fontan operation with delayed transcatheter closure of atrial septal defect. Improved results in high-risk patients. AB - Ten patients, each with two or more risk factors for morbidity and death, underwent a fenestrated Fontan procedure in which a 4 to 6 mm circular fenestration was left between the systemic and pulmonary venous chambers. None died; a similar group of high-risk patients without fenestration had a mortality rate of 2 of 8. Patients with fenestration had significantly less drainage from the chest tube, less need for inotropic support, and shorter intensive care and hospital stays than did patients without fenestration. Comparison with a group of low-risk patients undergoing the Fontan operation showed no statistical difference in these postoperative parameters. Fenestrations were closed in all 10 patients at from 9 days to 6 months after operation by means of the transcatheter clamshell occluder device. Two patients had left pulmonary artery balloon angioplasty and three patients had other atrial communications closed with additional clamshell devices. During short-term follow-up periods averaging 18 months, all patients were clinically well; however, one patient with mitral atresia required reoperation for obstruction between the left atrium and the tricuspid valve, not related to the clamshell device. These data indicate that fenestration may be one method of achieving lower morbidity and mortality rates among high-risk patients undergoing the Fontan procedure. PMID- 1597969 TI - Anomalous origin of the left coronary artery. A twenty-year review of surgical management. AB - Children with anomalous origin of the left coronary artery from the pulmonary artery are at risk for myocardial infarction and death. Surgical management of this condition in children has evolved significantly during the past 20 years. Between 1970 and 1990, a total of 20 of these patients underwent surgical intervention at two institutions. Age at operation ranged from 3 weeks to 11 years (mean, 26 months). Twelve patients had congestive heart failure, three were in cardiogenic shock, and two had cardiac murmurs. Operative techniques included ligation (n = 9), subclavian artery anastomosis (n = 5), aortic implantation (n = 3), internal mammary artery anastomosis (n = 1), intrapulmonary tunnel from aortopulmonary window to coronary artery (n = 1), and cardiac transplantation (n = 1). The three deaths in the series occurred at 3 weeks, at 2 months, and at 9 years after ligation. There have been no deaths after establishment of a two coronary artery system or after transplantation. Two of the five patients who had subclavian artery anastomosis to the anomalous coronary artery have severe anastomotic stenosis and collateralization. For patients with anomalous origin of the left coronary artery from the pulmonary artery, we recommend direct aortic implantation of the anomalous coronary artery at the time of diagnosis. Intrapulmonary tunnel from aortopulmonary window to coronary artery, or aorta coronary bypass with internal mammary artery are recommended for children in whom aortic implantation is not anatomically feasible. Left coronary artery ligation is not indicated for these patients; those who have survived ligation should be considered for elective establishment of a two coronary artery system because of the risk of late death. PMID- 1597970 TI - Performance of a stentless xenograft aortic bioprosthesis up to four years after implantation. AB - Conventional biologic and mechanical prostheses have important limitations with regard to their hemodynamic characteristics and long-term durability. We evaluated the hemodynamic function of a stentless porcine aortic prosthesis in 10 patients by invasive pressure measurements and angiography with videodensitometry 8 +/- 4 days after operation, as well as by Doppler echocardiography 35 +/- 15 months after valve replacement. The early postoperative invasive study revealed a mean gradient of 8 +/- 6 mm Hg across the prosthesis, no regurgitation in eight patients, and mild regurgitation, defined as less than 20% regurgitant fraction, in the remaining two patients. The late postoperative Doppler echocardiographic study revealed a mean gradient across the aortic prosthesis of 6 +/- 3 mm Hg, mean Doppler-derived valve orifice area of 1.8 +/- 0.6 cm2, and color Doppler flow velocity mapping suggested no regurgitation in eight patients and mild regurgitation in two patients corresponding to early postoperative angiography. None of the 10 patients received anticoagulation therapy. The clinical course of all patients was without incident. This stentless aortic bioprosthesis may offer hemodynamic advantage; however, further studies are needed to allow comparison with conventional mechanical and biologic prostheses. PMID- 1597972 TI - Coronary artery bypass grafting in patients with poor ventricular function. Cardiovascular Surgeons of the University of Toronto. AB - Although patients with severe ventricular dysfunction have improved long-term survival times after coronary bypass procedures, operative morbidity and mortality rates remain high. This study was designed to identify the contemporary risk factors for isolated coronary artery bypass grafting in this high-risk subgroup. Between January 1982 and December 1990, a total of 12,471 patients underwent isolated coronary artery bypass grafting. The 9445 patients with preoperative ejection fractions greater than 40% had a lower operative mortality rate (2.3%) than that of the 2539 patients with ejection fractions between 20% and 40% (4.8%) and that of the 487 patients with ejection fractions less than 20% (9.8%; p less than 0.001). However, patients with ejection fractions of less than 20% were demographically distinct from those with higher ejection fractions. This group was older, with fewer women, a higher frequency of left main stenosis, and more frequent requirement of urgent operation for unstable angina. The risk factors for operative death also varied with preoperative ejection fraction. The traditionally accepted risk factors--urgency of operation, left main coronary artery stenosis, reoperation, sex, and age--were predictive of risk of operative death for patients with ejection fractions greater than 40%. The risk of operative death for patients with ejection fractions between 20% and 40% was predicted by urgency of operation, reoperation, sex, myocardial protection, and age. The only predictor of risk of operative death for patients with ejection fractions less than 20% was urgency of operation. Patients undergoing isolated coronary artery bypass grafting who have severe ventricular dysfunction are therefore a highly selected, high-risk subgroup of patients who risk depends on the urgency of operation. Strategies to improve the results in these patients should be focused on patient selection, improvement of myocardial protection, and more aggressive preoperative treatment of myocardial ischemia. PMID- 1597971 TI - The Monostrut Bjork-Shiley valve. Seven years' experience. AB - The results of cardiac valve replacement with the Monostrut Bjork-Shiley prosthesis (Shiley, Inc., Irvine, Calif.) during a 7-year period are presented. A total of 984 valves were implanted in 820 patients from May 1983 to April 1990. Aortic valve replacement was performed in 378 patients, mitral replacement in 294, and multiple replacement in 148. In addition, 180 patients (22%) underwent associated procedures. Mean age was 52.6 +/- 11 years. Operative (30 days) mortality was 5.9% (49 patients): 3.9% (15 patients) for aortic, 7.8% (23 patients) for mitral, and 7.4% (11 patients) for multiple valve replacement. All patients were given long-term anticoagulation therapy. Follow-up was 99% complete (eight patients were lost to follow-up), with a closing interval of 3 months, and totaled 2422 patient-years. Valve-related complications, expressed as percentage event-free (+/- standard error) at seven years were as follows: structural deterioration, 100%; nonstructural dysfunction, 98.3% +/- 0.6%; thromboembolism, 90.2% +/- 1.7%; anticoagulant-related hemorrhage, 88.7% +/- 2.8%; and prosthetic valve endocarditis, 98.1% +/- 0.8%. There were no cases of valve thrombosis. Actuarial survival (free from operative, valve-related, and sudden death) was 88.4% +/- 1.2% at 7 years. Freedom from reoperation was 96.8% +/- 0.1%. Probability of being free from all valve-related morbidity and mortality was 70% +/- 3%, and 708 (93%) of the survivors were in New York Heart Association class I or II. Serial Doppler echocardiograms were done prospectively in 243 patients (with 154 aortic and 120 mitral prostheses), both postoperatively and at regular intervals up to 3 years. Mean prosthetic gradients ranged from an average of 20.9 to 7 mm Hg in the aortic prostheses (21 to 29 mm) and from 6.1 to 4.8 mm Hg in the mitral prostheses (25 to 31 mm). The gradients in each patient did not change significantly during the follow-up period. Our 7 year's experience with the Monostrut valve shows a low rate of valve-related complications, a durable design, and good hemodynamic and functional results. PMID- 1597973 TI - Time-course of medial and intimal thickening in pig venous arterial grafts: relationship to endothelial injury and cholesterol accumulation. AB - With use of an established model of pig saphenous vein grafts in the carotid artery, the time-course of the following changes was related: (1) medial and intimal size by morphometry of transverse sections, (2) cell number by deoxyribonucleic acid concentration, (3) cell density by deoxyribonucleic acid concentration per milligram wet weight and by counting nuclei in transverse sections, (4) endothelial morphology by scanning electron microscopy, and (5) cholesterol concentration. In the first week after grafting, medial and intimal thickening occurred associated with an increase in cell number. Between 1 and 4 weeks after grafting, further rapid medial and intimal thickening occurred with no further increase in cell number but with a reduction in cell density, which suggested that cell migration, hypertrophy, and the laying down of extracellular matrix were responsible. Between 4 and 39 weeks after grafting, a slower increase in medial and intimal size occurred, associated with a parallel increase in cell number and no further change in cell density. The endothelium of grafts showed only localized abnormalities, including loss of cells and leukocyte adhesion, either 1 or 4 weeks after grafting. Cholesterol concentration was slightly elevated 1 week after grafting but returned to values similar to those in vein by 4 weeks after grafting. Distention to 600 mm Hg during surgical preparation of vein for grafting resulted in lower graft patency after either 1 or 4 weeks and caused significant medial and endothelial injury. Distention did not, however, affect changes in medial or intimal size, deoxyribonucleic acid, or cholesterol concentration caused by grafting. We conclude that three processes contribute to medial and intimal thickening, namely: (1) an initial phase of rapid smooth muscle cell proliferation, (2) smooth muscle cell migration, hypertrophy, and synthesis of extracellular matrix, and (3) a late phase of slower smooth muscle cell proliferation. The incomplete late suppression of smooth muscle cell proliferation occurs despite regeneration of a morphologically intact endothelium and in the absence of progressive cholesterol accumulation. PMID- 1597975 TI - Transesophageal echocardiography in the emergency surgical management of patients with aortic dissection. AB - The diagnostic accuracy and benefit of transesophageal echocardiography were investigated in 32 patients with suspected aortic dissection. Results of transesophageal echocardiography were compared with surgical assessment. The Stanford classification was used for differentiation of dissection type. Examination time was 5 to 15 minutes. Twenty-eight patients were correctly identified to have aortic dissection; four patients had nondissecting aneurysms of the ascending aorta. Both sensitivity and specificity for detection of aortic dissection were 100%. Type of dissection was misdiagnosed in one patient. Classification of dissection type was correct in 96%. The primary entry site was correctly identified in 25 patients (89%). Aortic regurgitation was found in 57% of patients. Pericardial effusion was detected in 21%, with tamponade in one patient. Myocardial infarction was suggested by transesophageal echocardiography in 7%, and 14% had significantly reduced left ventricular function. Eight patients underwent operation based on transesophageal echocardiography alone. Intraoperative transesophageal echocardiography, performed in 20 patients, verified retrograde flow in the true lumen after femoral cannulation. Transesophageal echocardiography documented postrepair persistence of the intimal flap in aortic segments that were not operated on in all patients. Secondary tears and flow in the false lumen were detected in 35% of patients. We conclude that transesophageal echocardiography allows expedient and accurate diagnosis and classification of aortic dissection, and we recommend it as the primary bedside diagnostic modality. It can especially identify patients requiring surgical intervention without further delay caused by other diagnostic procedures. PMID- 1597974 TI - Atheroembolism from the ascending aorta. An emerging problem in cardiac surgery. AB - As the ages of patients undergoing cardiac operations have increased, noncardiac causes of death have increased. To identify these causes of death, we analyzed the autopsy findings in 221 patients undergoing myocardial revascularization or valve operations between 1982 and 1989. Mean age was 65.6 +/- 9.5 years and the range was from 32 to 94 years; 130 patients (58.8%) were male. Autopsies were complete in 129 patients (58.4%) and limited to the chest and abdomen in the remainder. Embolic disease was identified in 69 patients (31.2%). Atheroemboli or abnormalities consistent with atheroemboli were identified in 48 patients (21.7%). Fourteen patients had thromboembolism and 7 had disseminated intravascular coagulation. The prevalence of atheroembolic disease increased dramatically from 4.5% in 1982 to 48.3% in 1989 (p = 0.001). Atheroembolic disease was found in the brain in 16.3% of patients, spleen in 10.9%, kidney in 10.4%, and pancreas in 6.8%. Thirty (62.5%) of the 48 patients had multiple atheroembolic sites. Atheroemboli were more common in patients undergoing coronary artery procedures (43/165; 26.1%) than in those undergoing valve procedures (5/56; 8.9%) (p = 0.008). There was a high correlation of atheroemboli with severe atherosclerosis of the ascending aorta. Atheroembolic events occurred in 46 of 123 patients (37.4%) with severe disease of the ascending aorta but in only 2 of 98 patients (2%) without significant ascending aortic disease (p less than 0.0001). Forty-six of 48 patients (95.8%) who had evidence of atheroemboli had severe atherosclerosis of the ascending aorta. There was a direct correlation between age, severe atherosclerosis of the ascending aorta, and atheroemboli. Incremental risk factors for atheroembolic are peripheral vascular disease and severe atherosclerosis of the ascending aorta. PMID- 1597976 TI - Morbidity, mortality, and early results of single versus bilateral lung transplantation for emphysema. AB - Both single lung transplantation and bilateral lung transplantation have been successful in patients with chronic obstructive pulmonary disease. Limited availability of donor lungs dictates wider use of single lung transplantation as long as this procedure provides a comparable functional result at less risk. Early morbidity, mortality rates, and functional results were compared in 32 consecutive patients undergoing either single or bilateral lung transplantation for end-stage chronic obstructive pulmonary disease. When pretransplantation and posttransplantation values of forced expiratory volume in 1 second, single breath diffusing capacity, total lung capacity, arterial oxygen tension, and 6-minute walking distance were compared, statistically significant improvement (p less than 0.01) was seen in both groups. However, significantly higher values (p less than 0.01) were attained for forced expiratory volume in 1 second, single breath diffusing capacity, and arterial oxygen tension in the bilateral transplantation group than in the single lung transplantation group. Patients receiving bilateral lung transplants were at greater risk for postoperative complications, especially cardiac arrhythmias and bronchial anastomotic defects. Actuarial survival for the single lung transplantation group was 93% at 1 year, versus 87% at 6 months and 71% at 1 year for the bilateral lung transplantation group. The optimal transplantation procedure for patients with chronic obstructive pulmonary disease has not been determined. Longer follow-up periods are needed to define better the roles of bilateral and single lung transplantation in this group of patients. PMID- 1597977 TI - Reliable eighteen-hour lung preservation at 4 degrees and 10 degrees C by pulmonary artery flush after high-dose prostaglandin E1 administration. AB - Pulmonary preservation is improved by hypothermia, but the optimal preservation temperature is not known. The effects of two different preservation temperatures, 4 degrees and 10 degrees C, on lung function were studied in a canine left lung allograft survival model allowing selective perfusion of either lung. After donor treatment with high-dose prostaglandin E1, (25 micrograms/kg), lungs were flushed with modified Euro-Collins solution (50 ml/kg) and stored in Euro-Collins solution for 18 hours at 4 degrees C in group I (n = 8) and 10 degrees C in group II (n = 6). Pulmonary gas exchange and hemodynamics were compared on the day of transplantation (day 0) and 3 days later (day 3). Rapid, high-flow, low-pressure flush was achieved uniformly in both groups (flush time: group I, 35.1 +/- 2.4 second; group II, 35.3 +/- 3.0 seconds; p = 0.96; flush pressure: group I, 9.8 +/ 0.7 mm Hg; group II, 10.1 +/- 1.1 mm Hg; p = 0.8). Transplanted lungs provided similar excellent oxygenation in both groups on day 0 (arterial oxygen tension, group I, 451 +/- 82 mm Hg; group II, 497 +/- 37 mm Hg; p = 0.61; inspired oxygen fraction = 1.0) and day 3 (arterial oxygen tension, group I, 551 +/- 57 mm Hg; group II, 587 +/- 19 mm Hg; p = 0.55), with a statistically significant improvement from day 0 to day 3 in both groups (group I, p = 0.034; group II, p = 0.038). There was no difference in arterial carbon dioxide tension, base excess, cardiac output, blood pressure or pulmonary artery pressure between the two groups. We conclude that a large bolus of prostaglandin E1 into the pulmonary artery produces a high-flow, low-pressure flush with modified Euro-Collins solution; with this technique, equivalent, reliable 18-hour lung preservation can be achieved at 4 degrees and 10 degrees C flush and storage temperatures. PMID- 1597978 TI - Poloxamer 188 improves neurologic outcome after hypothermic circulatory arrest. AB - Poloxamer 188, an amphipathic copolymer with cytoprotective properties, was investigated as a means of improving neurologic outcome after a prolonged period (150 minutes) of deep hypothermic circulatory arrest. Dogs were perfusion cooled and surface cooled to 10 degrees C, the heart was arrested for 150 minutes, and then the dogs were rewarmed and weaned from bypass. Seven dogs were treated with poloxamer 188 before and after deep hypothermic circulatory arrest. Six control dogs were treated with saline. Surviving dogs were evaluated for 1 week after deep hypothermic circulatory arrest for neurologic deficits or behavioral changes. Neurologic outcome was graded by the following system: grade 1, death within the observation period; grade 2, comatose; grade 3, holds head up; grade 4, sits up; grade 5, stands; grade 6, normal in both behavior and gait. There were no deaths in the seven poloxamer 188-treated animals versus three deaths in the six control dogs. Poloxamer 188-treated dogs also manifested significantly less neurologic dysfunction after deep hypothermic circulatory arrest than did the control group (p less than 0.003). This study shows that poloxamer 188 has a significant impact in improving neurologic outcome after exceptionally long periods of deep hypothermic circulatory arrest. PMID- 1597979 TI - Global myocardial ischemia and reperfusion impair endothelium-dependent relaxations to aggregating platelets in the canine coronary artery. A possible cause of vasospasm after cardiopulmonary bypass. AB - Experiments were designed to determine whether endothelial cell injury contributes to increased coronary vascular tone after global cardiac ischemia and reperfusion. Canine hearts were exposed to global ischemia for 45 minutes and were reperfused for 60 minutes. Rings (5 to 6 mm long) of the left anterior descending coronary artery from reperfused hearts and from normal (control) hearts were suspended for isometric force measurement in organ chambers containing physiologic salt solution (37 degrees C, and 95% oxygen and 5% carbon dioxide). After contraction with prostaglandin F2 alpha, reperfused coronary arteries had significant impairment of endothelium-dependent relaxations to aggregating platelets (52% +/- 12% relaxation versus 102% +/- 11% for control segments; p less than 0.05). Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to the receptor-dependent agonist acetylcholine and the platelet-derived compounds adenosine diphosphate and serotonin. Importantly, endothelium-dependent relaxations to the non-receptor-dependent agonist A23187 were normal after ischemia and reperfusion. Quiescent (noncontracted) reperfused arterial rings lost the ability to counteract the constrictive effect of aggregating platelets on the coronary vascular smooth muscle (24% +/- 7% contraction versus 5% +/- 2% relaxation for control segments; p less than 0.05). Endothelium-independent contractions to potassium chloride and prostaglandin F2 alpha were similar in reperfused and normal arteries. Also, endothelium-independent relaxations to nitric oxide and isoproterenol were comparable in reperfused arteries and normal vessels. Thus global cardiac ischemia and reperfusion impair the normal endothelium-dependent relaxations to aggregating platelets and other receptor-dependent vasoactive drugs. This impairment of platelet-mediated coronary vasodilation may explain increased coronary vascular tone after cardiopulmonary bypass and could be an important pathophysiologic mechanism of postoperative coronary vasospasm. PMID- 1597980 TI - The effect of warm heart surgery on postoperative bleeding. AB - The effects of normothermic systemic perfusion (35 degrees to 37 degrees C; n = 73) were compared with those of moderately hypothermic systemic perfusion (25 degrees to 29 degrees C; n = 73) with respect to blood loss, transfusion requirements, and platelet levels in 146 patients undergoing isolated, primary coronary artery bypass grafting. In addition, most patients were given an antifibrinolytic medication during operation as follows: tranexamic acid (10 gm intravenously; n = 63), epsilon-aminocaproic acid (15 gm intravenously; n = 63), or no drug as a control. (n = 20). Normothermic patients tended to bleed less at 24 hours (warm, 864 +/- 42 ml and cold, 918 +/- 68 ml), but these differences were not statistically significant. Patients receiving either tranexamic acid or epsilon-aminocaproic acid, regardless of perfusion temperature, bled less after 6, 12, and 24 hours than did cold control patients (p less than 0.05). Warm control patients also bled less than did cold control patients after 6 or 12 hours (p less than 0.05), and neither drug further reduced blood loss in these patients. Circulating platelet levels were better preserved in patients receiving either tranexamic acid or epsilon-aminocaproic acid and in patients with warm perfusion and no drug than in cold control patients. Normothermic systemic perfusion, tranexamic acid, and epsilon-aminocaproic acid each reduced postoperative blood loss and preserved platelets. PMID- 1597981 TI - Arterial ketone body ratio during and after cardiopulmonary bypass. AB - This study is the first to investigate the alteration in hepatic function during and after cardiopulmonary bypass in 30 patients by measuring the arterial ketone body ratio, an index of mitochondrial redox potential (oxidized nicotinamide adenine dinucleotide/reduced nicotinamide-adenine dinucleotide). Although the preoperative arterial ketone body ratio was within normal limits (1.24 +/- 0.63), it decreased markedly 5 minutes after the start of cardiopulmonary bypass to 0.35 +/- 0.12 and remained at this low level throughout bypass. After bypass it continued to rise in a time-dependent fashion, returning to its preoperative level by the morning of the second postoperative day in normal convalescent patients. However, the ratio recovered more slowly in patients who required prolonged circulatory or respiratory support than in other patients. Thus we suggest that cardiopulmonary bypass had deleterious effects on the hepatic mitochondrial redox potential, which may contribute to homeostatic derangements and metabolic abnormalities. PMID- 1597982 TI - Heparin resistance after intraoperative platelet-rich plasma harvesting. AB - Records of anticoagulation for cardiopulmonary bypass from 58 patients who underwent elective coronary artery revascularization were analyzed to determine whether the harvesting of autologous platelet-rich plasma produces heparin resistance. The effect of preoperative heparin therapy on anticoagulation for cardiopulmonary bypass after harvesting of platelet-rich plasma was also evaluated. Patients were grouped by presence of preoperative heparin therapy and type of blood component harvested before cardiopulmonary bypass, including platelet-rich plasma, autologous whole blood, both, or neither. The dose of heparin required to initiate and to maintain anticoagulation for cardiopulmonary bypass was determined for each patient, and the groups were compared by two-way analysis of variance. Significantly more heparin was required to maintain anticoagulation for cardiopulmonary bypass in the platelet-rich plasma group than in the groups receiving autologous whole blood or no blood products. More heparin was also required to initiate and to maintain anticoagulation for cardiopulmonary bypass after preoperative heparin therapy. These results reinforce the concept that anticoagulation during cardiopulmonary bypass must be carefully monitored, and increased vigilance may be warranted in patients after harvesting of platelet rich plasma. PMID- 1597983 TI - Hemodynamic effects of prostaglandin E1 and isoproterenol early after cardiac operations for mitral stenosis. AB - Patients with mitral stenosis and some degree of right ventricular failure may benefit from inotropic or pulmonary vasodilator drugs in the early postoperative period. Thirty patients undergoing an operation for mitral stenosis were randomized into three groups. In group I (n = 10), isoproterenol (5 micrograms/kg/min) was started in the immediate postoperative period. In group P (n = 10), prostaglandin E1 (0.08 microgram/kg/min) was given, and in group C, the control group (n = 10), no drugs were used. After the operation and before drug therapy was begun, basal measurements of cardiac index, mean pulmonary arterial and mean arterial pressures, and pulmonary vascular resistance were taken. Measurements were repeated at 6, 12, and 24 hours. Mean measurements of cardiac index (basal up to 24 hours) were as follows: 1.39 +/- 0.3, 1.92 +/- 0.4, 2.4 +/- 0.5, and 2.34 +/- 0.3 L/min/m2 for group C; 1.54 +/- 0.5, 2.64 +/- 0.4, 2.68 +/- 0.7, and 2.2 +/- 0.6 L/min/m2 for group I, and 1.57 +/- 0.3, 2.2 +/- 0.6, 2.72 +/ 0.7, and 2.27 +/- 0.4 L/min/m2 for group P (p less than 0.05 between groups C and I at 6 and 12 hours). Mean pulmonary artery pressures were as follows: 19.5 +/- 3.2, 24.8 +/- 7, 27.7 +/- 7.3 and 28.8 +/- 5.7 mm Hg in group C; 21.4 +/- 8.7, 25.7 +/- 7.2, 26.4 +/- 7, and 29.4 +/- 8.6 mm Hg in group I, and 19.1 +/- 4, 19.2 +/- 3, 20.4 +/- 6, and 20.7 +/- 5 mm Hg in group P (p less than 0.05, group P versus groups C and I at 6, 12, and 24 hours). Mean pulmonary vascular resistances were as follows: 3.9 +/- 2.4, 3.9 +/- 1, 3.36 +/- 2, and 3.2 +/- 1.4 Wood units in group C; 4.84 +/- 4, 3.37 +/- 2.2, 3.69 +/- 3, and 4.69 +/- 4.1 Wood units in group I, and 3.29 +/- 1.3, 1.71 +/- 0.5, 1.61 +/- 0.5, and 1.96 +/- 0.8 Wood units in group P (p less than 0.05, group P versus groups C and I at 6, 12, and 24 hours). There was no difference in mean systemic arterial pressure among the three groups. Our results indicate that patients subjected to mitral valve operations have a low cardiac index. Isoproterenol increases cardiac index but has little effect on pulmonary resistance. At low doses, prostaglandin E1 effectively decreases pulmonary vascular resistance without altering systemic arterial pressure or heart rate. PMID- 1597984 TI - Ischemia of the interventricular septum. A mechanism of right ventricular failure during mechanical left ventricular assist. AB - Right ventricular failure has been noted in up to 25% of patients requiring a left ventricular assist device. Altered septal motion or function is one proposed mechanism of right ventricular failure during left heart bypass. We studied the effect of regional ischemia and reperfusion of the interventricular septum on right ventricular function during complete left heart bypass. In six calves the septal perforating branches of the proximal left anterior descending coronary artery were isolated for intermittent occlusion. Complete left heart bypass was established with a Pierce-Donachy left ventricular assist device. Right and left ventricular function were studied with two-dimensional echocardiography and with intraventricular pressure monitors. Establishment of left heart bypass did not significantly affect right ventricular developed pressure, right ventricular end diastolic area, or right ventricular fractional change in area. Left heart bypass significantly (p less than 0.001) decreased percent systolic septal wall thickening. Septal ischemia during left heart bypass resulted in a decrease in right ventricular developed pressure (p = 0.09), significant increase in right ventricular end-diastolic area (p = 0.002) and significant decrease in right ventricular fractional change in area (p less than 0.001), and a further decrease in interventricular septal wall thickening (p = 0.016). The interventricular septum became thin with flattening of its normal contour. Septal reperfusion resulted in right ventricular recovery with significant improvement in all factors (p less than 0.02). Similar results were documented during a second episode of septal ischemia with recovery after septal reperfusion. In some cases, septal ischemia may be an important factor in the development of right ventricular failure during left heart bypass. PMID- 1597985 TI - Influences of cardiopulmonary bypass, temperature, cardioplegia, and topical hypothermia on cardiac innervation. AB - The effects of normothermic and hypothermic cardiopulmonary bypass, crossclamping of the aortic root, cold cardioplegia, as well as epicardial application of iced slush, on the efficacy of the efferent sympathetic nervous system to augment the heart and the efferent parasympathetic nervous system to depress the heart were studied in anesthetized dogs. Cardiac rate and force are augmented by stimulation of the intrathoracic efferent sympathetic nervous system and reduced by stimulation of the intrathoracic efferent parasympathetic nervous system. After cardiopulmonary bypass, which included systemic and topical hypothermia, aortic crossclamping, and crystalloid cardioplegia, the augmentor effects of the efferent sympathetic nervous system were obtunded whereas the depressor effects exerted by the efferent parasympathetic nervous system were not. Direct cardiac myocyte augmentor responses induced by isoproterenol were unaffected by these interventions. Normothermic cardiopulmonary bypass, hypothermic cardiopulmonary bypass, crossclamping of the aorta, or cold cardioplegia did not result in blunting of the efferent sympathetic cardiac nervous system. Significant blunting of cardiac augmentation induced by the efferent sympathetic nervous system occurred after topical application of iced slush alone. These data demonstrate that blunting of the efferent sympathetic, but not parasympathetic, innervation of the heart occurs after cardiopulmonary bypass, which presumably is primarily due to altering the function of subepicardial efferent sympathetic axons by topical hypothermia and not due to altered cardiac myocyte function. These data imply that after cardiopulmonary bypass involving the procedures described, the ability of the efferent sympathetic nervous system to support cardiac rate and force is transiently impaired. PMID- 1597986 TI - Dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension. An experimental study. AB - The efficacy of dynamic cardiomyoplasty for hemodynamic support during acute pulmonary hypertension was studied. Five dogs underwent a right latissimus dorsi cardiomyoplasty. Each dog was later studied in a short-term experiment. A graded acute pulmonary hypertension was induced by infusion of glass microspheres into the pulmonary artery. This resulted in decrease in pulmonary artery flow, systemic pressure, and systemic flow. The cardiomyoplasty was then stimulated with a new R wave synchronous rate-responsive pulse-train stimulator (Prometheus system). This pacemaker delivers a pulse train with the duration of stimulation determined as a proportion of the RR interval. At an optimal level of hemodynamic impairment, the dynamic cardiomyoplasty was able to immediately improve pulmonary artery flow 26.4% +/- 5.84% (standard error of the mean) (p less than 0.005, paired t test), mean systemic arterial pressure 11.6% +/- 3.7% (p less than 0.05), and thoracic aortic flow 15.7% +/- 6.3% (p less than 0.05). The degree of improvement in hemodynamic variables could be correlated with the magnitude of hemodynamic impairment present (e.g., r = 0.78; p less than 0.005 for pulmonary blood flow). We conclude that a significant beneficial effect of dynamic cardiomyoplasty on hemodynamics in short-term canine pulmonary hypertension is demonstrated in this study. Thus cardiomyoplasty may be useful in patients with right heart failure associated with increased pulmonary vascular resistance. PMID- 1597987 TI - Effects of dynamic cardiomyoplasty on indices of left ventricular systolic and diastolic function in a canine model of chronic heart failure. AB - The effects of cardiomyoplasty were evaluated with multiple-gated equilibrium radionuclide angiocardiography and catheterization in a canine model of chronic heart failure. Doxorubicin was administered to 12 dogs at a dose of 1 mg/kg/wk intravenously for 10 weeks. Left ventricular ejection fraction was reduced from a mean of 53.6% +/- 3.4% to 33.5% +/- 2.3% preoperatively. Two dogs died of presumed arrhythmia during this period. Cardiomyoplasty with the left latissimus dorsi muscle was performed on 10 dogs. The muscle was wrapped around both the left and right ventricles. Five dogs died of infection or arrhythmia after the operation. Postoperatively the muscle remained unstimulated for 2 weeks to allow adhesion to the heart. After this period, the latissimus dorsi muscle was conditioned by a progressive stimulation protocol. After the muscle was conditioned, multiple-gated equilibrium radionuclide angiocardiography studies showed that left ventricular global ejection fraction was 18.4% +/- 7.2% at 0 volts (nonstimulation), 26.2% +/- 3.7% at 5-volt stimulation (p less than 0.05), and 31.0% +/- 5.4% at 10-volt stimulation (p less than 0.05). Regional ejection fractions in low lateral, apical, and low septal regions at 5 volts and 10 volts were higher than those at 0 volts (p less than 0.05). Regional wall motion (percent radial shortening) of the low lateral region was higher than that during nonstimulation (p less than 0.05). Peak emptying rate was 2.07 +/- 0.95 end diastolic counts per second at 0-volt, 3.10 +/- 0.67 at 5-volt, and 3.34 +/- 0.89 at 10-volt stimulation (p less than 0.05). Peak filling rate was 1.81 +/- 0.52 end-diastolic counts per second at 0-volt, 2.67 +/- 1.18 at 5-volt, and 3.11 +/- 0.65 at 10-volt stimulation (p less than 0.05). Cardiac catheterization data showed a nonsignificant increase in left ventricular rate of pressure rise with increasing voltage (1302 +/- 355 mm Hg/sec at 0 volts, 1450 +/- 413 mm Hg/sec at 5 volts, and 1568 +/- 455 mm Hg/sec at 10 volts). Left ventricular systolic pressures were unchanged. End-diastolic pressures decreased (11.2 +/- 1.48 mm Hg at 0 volts, 10.4 +/- 2.30 mm Hg at 5 volts, and 9.6 +/- 1.52 at 10 volts; p less than 0.05). These data show that cardiomyoplasty can improve indices of systolic and diastolic function in a canine model of chronic heart failure. PMID- 1597988 TI - Use of a double-lumen tracheostomy tube after single lung transplantation. PMID- 1597990 TI - Total cavopulmonary derivation with the use of a pediculated pericardial tube between the inferior vena cava and the pulmonary artery trunk in tricuspid atresia. PMID- 1597989 TI - Endobronchial chondromatous hamartoma: a rare cause of lobar collapse treated by endoscopic removal. PMID- 1597991 TI - The open sternotomy wound and risk of acute hemorrhage. PMID- 1597992 TI - Avoidance of steal phenomena by thorough internal mammary artery dissection. PMID- 1597993 TI - Retained intraaortic balloon assist device. PMID- 1597994 TI - Recent development of studies on traditional Chinese medicine in prophylaxis and treatment of AIDS. PMID- 1597995 TI - Prophylactic and therapeutic effects of acupuncture on simple obesity complicated by cardiovascular diseases. AB - In order to understand the prophylactic-therapeutic effects of acupuncture and moxibustion in simple obesity complicated by cardiovascular diseases, we have observed in 102 cases the changes of pathogenetic and hazardous factors and the regulating function of vegetative nerves on cardiovascular activities. The results showed that the therapeutic effect of acupuncture and moxibustion was good with a total effective rate of 88.24%. At the same time, acupuncture and moxibustion were found to have a benign conversion effect on the loin hip ratio (the pathogenetic factor), the arteriosclerotic index (the hazardous factor), and the vegetative nerve function of regulating the heart and blood vessels (the equilibrium indices of the vegetative nervous system). All this suggests that acupuncture is a treatment of choice for obesity and an important method of preventing and treating complicating cardiovascular diseases. PMID- 1597996 TI - Clinical observations on treatment of 120 cases of coronary heart disease with herba epimedii. PMID- 1597997 TI - Acupuncture treatment of rheumatoid arthritis and exploration of acupuncture manipulations. PMID- 1597998 TI - Treatment of rheumatoid arthritis by warming needle. PMID- 1597999 TI - A clinical study on acupuncture treatment of pediatric cerebral palsy. PMID- 1598000 TI - Clinical application of acupoint tianshu. AB - Acupoint Tianshu (St 25), in combination with other adjuvant points as indicated by symptom differentiation, are very effective in the treatment of diseases of the digestive system. The needles are inserted perpendicularly to a depth of 1 1.5 cun, according to the thickness of body fat of the patient, and maneuvers of thrusting, lifting and rotation were done for reducing the exuberant type and reinforcing the deficient type. Most patients benefit from this therapeutic modality. PMID- 1598001 TI - Therapeutic effects of using acupoint chiqian. PMID- 1598002 TI - Clinical observations on the treatment of 50 cases of stiff neck by acupuncture. PMID- 1598003 TI - Some important links in promoting the curative effect of acupuncture. PMID- 1598004 TI - The Chinese 'health-giving diet' abroad. PMID- 1598005 TI - 34 cases of herpes zoster treated by moxibustion at dazhui (du 14). PMID- 1598006 TI - The detailed articles of the Plan for the Proficiency Examination for International Acupuncture & Moxibustion Professionals (for Trial Implementation). PMID- 1598007 TI - [The effects of prostacyclin on oxygen transport in adult respiratory distress syndrome]. AB - BACKGROUND: Patients with the adult respiratory distress syndrome (ARDS) present a deficit of tissue oxygenation which may be unmasked if increases in oxygen uptake (VO2) are observed when increases in oxygen delivery (DO2) are induced. Prostacyclin is a drug to which microvasodilator effects have been attributed and it has been proposed as an efficient agent for increasing histic enhancement of oxygen. METHODS: An infusion of prostacyclin was administered to 13 patients diagnosed with ARDS at doses of 10, 20, and 30 ng/kg per minute monitored with a Swan-Gatz catheter. RESULTS: The values are expressed as the percentage median of the increase with p less than 0.05 being considered as statistically significant. Prostacyclin significantly increased DO2 (10, 18 and 15% at the different doses). The VO2 rose significantly only following the first dose (13%). There was a correlation between the increase of DO2 and that of VO2 following the administration of the first dose (r = 0.70, p = 0.017. An important systemic vasodilator and pulmonary effect was observed accompanied by increases in the pulmonary (20, 56 and 59%) and reductions of PaO2 (-33.5, -40 and -48%) which may have been due to inhibition of hypoxic vasoconstriction. CONCLUSIONS: Prostacyclin is efficient for unmasking a lack of oxygen in patients with adult respiratory distress syndrome. The deleterious effects of this drug on systemic hemodynamics and on gaseous interchange makes not only the monitorization of arterial pressure but also of the parameters of gaseous interchanges necessary in these patients. PMID- 1598008 TI - [Diet and hypertriglyceridemia: influence of dietary modifications on plasma lipids, lipoproteins and apoproteins in patients with primary hypertriglyceridemia]. AB - BACKGROUND: To investigate the influence of dietary changes on plasma lipoproteins and apoproteins in 10 patients with hypertriglyceridemia (plasma triglycerides greater than 1000 mg/dl). METHODS: A sequential study with three periods was designed: 1) Inclusion with uncontrolled free diet; 2) Two weeks of a diet with about 1000 calories/day, controlled with a daily survey; and 3) One week of "free" diet of about 2000 calories. At the end of the three periods the following were measured in each patient: weight, glycemia, plasma IRI and C peptide, plasma, triglycerides, cholesterol, chylomicron, VLDL, LDL and HDL cholesterol. At the end of the second and third periods the caloric and immediate principles intake were individually considered. RESULTS: A reduction in plasma cholesterol and triglycerides was observed in all cases after the caloric reduction, and also a disappearance of chylomicrons. The reduction of triglycerides took place in all lipoproteins. By contrast, after the low-calorie diet only the VLDL-cholesterol was reduced, while LDL- and HDL-cholesterol increased. The apo C-III/apo C-II ratio was significantly reduced after the low calorie diet. The plasma glycemia, IRI and C-peptide were negatively correlated with LDL-cholesterol and with the apo C-III/apo C-II ratio. The best model to explain the oscillations of plasma triglycerides depending on the diet was that including the three ingested immediate principles together with the total diet calories. CONCLUSIONS: During the caloric restriction there would be an increased catabolism of VLDL to LDL. This reduction would be mediated by C-III and C-II apoproteins, probably through the oscillations of plasma IRI. PMID- 1598009 TI - [Anthropometric study of the school population of the autonomic community of Murcia]. AB - BACKGROUND: The aim of this study was to know the anthropometric study of school children in Murcia in order to obtain parameters of present reference for our country and region. METHODS: A transversal study of the school population of the community of Murcia at Preschool, EGB, BUP and Technical School levels was carried out including 1,930 children between the ages of 4 and 17. These children were selected from a total of 242,596 proportionally chosen with respect to demography of each of the twelve regions in the area with weight, height and bicipital, tricipital, subscapular and abdominal skin folds being measured. RESULTS: The values obtained and classified by age, sex and regions of the autonomic community of Murcia exposed in tables, demonstrate the differences existing in all the parameters measured with those routinely used at an international and national level. CONCLUSIONS: The differences found clearly justify the need to compare the regional antropometric alterations with the "reference parameters" obtained in Spain and Murcia for which other studies concerning the same would be advisable. PMID- 1598010 TI - [Neurobiology of schizophrenia]. PMID- 1598011 TI - [Cancer and pregnancy]. PMID- 1598012 TI - [Cardiac tamponade as the first manifestation of carcinoma of the esophagus]. AB - Purulent pericarditis (PP) is a very infrequent entity, and its finding generally implies infection in an adjacent or distant foci. Another possible cause not implying the existence of an associated infectious process is the presence of an esophago-pericardial fistula. The case of a patient with a neoplasm of the esophagus is described in which the form of presentation of the disease was cardiac tamponade by PP. Revision of the literature identified only one other case of PP secondary to an esophago-pericardial fistula of malignant origin. PMID- 1598014 TI - [Thrombocytopenia associated with HIV infection]. PMID- 1598013 TI - [Conceptual bases for the design of an instrument for measuring the quality of life in those affected with health problems: the quality of life index of the Nursing School of the University of Valencia]. PMID- 1598015 TI - [Thrombosis of the axillary vein and pleural mesothelioma]. PMID- 1598016 TI - [Seroprevalence of the hepatitis C virus in donors and in high and low risk groups in Salamanca]. PMID- 1598017 TI - [Behaviors associated with shyness: transcultural aspects]. PMID- 1598018 TI - [Contralateral asterixis in hematoma of basal ganglia]. PMID- 1598019 TI - [Encephalopathy caused by phenytoin]. PMID- 1598020 TI - [Acute bacterial parotiditis and Sjogren's syndrome]. PMID- 1598021 TI - [Severe neurologic toxicity from oral acyclovir]. PMID- 1598022 TI - Effects and mechanism of low [K]o on the critical potential of effective refractory period in guinea pig ventricular muscle cells. AB - 1.5 mM KCl Tyrode's solution enabled the critical potential (-55-60 mV) of effective refractory period to shift in a positive direction in guinea pig ventricular muscle cells. In 1.5 mM KCl Tyrode's solution, the probability of testing AP's initial potential positive to -54 mV in the repolarizing phase was as high as 80% (n = 10), but the percentage in 4.5 mM [K]o group was only 11% (n = 35). The mean value of the positive shift was 30.2 +/- SD 17 mV. Testing APs had higher values of overshoots (mean = 23 +/- 13.8 mV); their mean Vmax was 98 V/s. Early after depolarization and positive inotropic effects appeared. 13.5 mM KCl, in contrast to 1.5 mM KCl, produced contrary effects. Phenomena indicated that early after depolarization in low [K]o was associated with the positive shift of critical potential of effective refractory period. Above-mentioned effects of 1.5 mM KCl could not be completely eliminated by verapamil, but could be abolished by an inactivation promoting agent of sodium channel, lidocaine 7.4 x 10(-5) M (n = 10). The results suggest that accelerating recovery time and shifting recovery potential in the positive direction of inactivated sodium channel might be the principal reasons for the effects of low [K]o. The role of the Na+ pump inhibitor, ouabain, was not similar to that of 1.5 mM KCl Tyrode's solution except for positive inotropic effect. PMID- 1598023 TI - Effect of electroacupuncture on the long-term diazepam-induced changes in regional GABA of mammalian central nervous system. AB - Single electroacupuncture (EA) exposure (10 Hz, 1 volt, 15 min) to long-term (15 consecutive days) diazepam (5 mg/kg/day, i.p.) treated adult male albino rats (120-140 g) potentiated the long-term diazepam-induced increase of GABAergic activity in thalamus (Th) but the long-term diazepam-induced inhibition of GABAergic activity in cerebral cortex (CC) and spinal cord (SC) was disinhibited under similar condition of treatment. These changes in brain regional GABAergic activity may be correlated with the inhibition of single EA-induced analgesia (EAA) under similar conditions of long-term diazepam treatment with single EA exposure. Single EA exposure alone, however, inhibited GABAergic activity in Th and pons-medulla (PM) with the development of EAA. Multiple EA (10 Hz, 1 volt, 10 min/day) exposure along with long-term diazepam for 15 consecutive days inhibited GABAergic activity in CC and SC which is similar to the effect observed with either multiple EA exposure or long-term diazepam alone. But in Th the multiple EA or long-term diazepam-induced increase in GABAergic activity was significantly potentiated with the co-treatment of multiple EA and long-term diazepam for 15 consecutive days. Although GABAergic activity in PM under multiple EA or long term diazepam treatment alone was not affected their (EA and diazepam) co exposures under long-term conditions significantly enhanced GABAergic activity in PM. These region specific characteristic changes in central GABAergic activity under long-term treatment of diazepam along with EA may thus explain the potentiation of multiple EA or long-term diazepam-induced analgesia (tail flick latency). PMID- 1598024 TI - Effects of administration route on pharmacokinetics of viloxazine in the rabbit. AB - The absorption of viloxazine chlorhydrate was investigated in ten rabbits. Each animal received the drug (15 mg/kg) by three routes: intravenous, gastric and duodenal. Viloxazine plasma concentrations were low when administered by gastric and duodenal routes compared to those after intravenous injection. Concentrations to peak were 1-2 times higher after duodenal than gastric administration. Times to peak were 23.0 +/- 4.7 min after gastric administration and 9.5 +/- 5.4 min after duodenal administration. A better absorption of viloxazine after administration occurred in the duodenum than in the stomach; these results agree with viloxazine pKa = 8.13. The other pharmacokinetic parameters such as half life, clearance and volume of distribution where the same irregardless of the administration route. PMID- 1598025 TI - Pharmacokinetic characterization of mitonafide in man. AB - The pharmacokinetic behavior of mitonafide after intravenous administration (1 h infusions) to patients (118-180 mg/m2) can be described by an open three compartment body model. Mitonafide distributes quasi-instantaneously in a central distribution volume of 102 l/m2 (median) from which it equilibrates with two peripheral compartments of 106 and 258 l/m2, respectively. Its disappearance from plasma is triexponential with half-lives of 0.28, 2.0 and 26.9 h, resulting in a clearance of 69 l/h/m2. This clearance is mainly due to the biotransformation of mitonafide leading among others to amonafide, N-acetyl-amonafide, and N-desmethyl amonafide, which build up substantial concentrations in plasma. Their quantitative importance in terms of exposures (AUC) relative to the parent compound are 86, 197 and 28%, respectively. Terminal elimination from plasma proceeds with half-lives of 34.3, 17.6 and 27.5 h. PMID- 1598026 TI - Glial fibrillary acidic protein stimulates proliferation and immunoglobulin synthesis of lymphocytes from Alzheimer's disease patients. AB - The level of anti-GFAP (glial fibrillary acidic protein) IgG antibody titer was assayed in sera of patients with Alzheimer's disease, multi-infarct dementia, and the age-matched control subjects. Significantly higher level of anti-CFAP titer was found in sera of Alzheimer's disease patients. The in vitro lymphocyte response was studied by stimulation with GFAP and interleukin 2 (IL-2). The lymphocytes of Alzheimer's disease patients showed higher proliferative response than those of the control by GFAP and IL-2 stimulation. The IgG secretion by lymphocytes from Alzheimer's disease patients was also stimulated by GFAP as well as by GFAP plus IL-2. The results demonstrate that the lymphocytes of Alzheimer's disease patients are more responsive to GFAP than those of the control subjects. PMID- 1598027 TI - Effects of lorazepam on the properties of brain polysomes. AB - This study determined the effects of acute administration of lorazepam (LRZ) on brain protein synthesis by examining the translational abilities of polysomal RNA under in vitro conditions compared to those produced by the CNS depressants, ethanol and pentobarbital. Lorazepam (2 mg/kg body weight), ethanol (4 g/kg body weight) or pentobarbital (40 mg/kg body weight) were given orally to 6-week old male Sprague-Dawley rats. Control groups were either untreated or received the vehicle sesame seed oil orally. The measurement of rectal temperature in each group before (baseline) and 60 min after drug administration showed no change in body temperature in the control or LRZ treated groups but there was a significant temperature drop in the ethanol and pentobarbital group. After 60 min of drug administration, experimental groups when compared to the controls showed significant inhibitions in the translational activities of the cerebral polysomes. The inhibition was most pronounced with polysomes from the LRZ treated group and was consistently observed over a 60 min time period. The findings suggest polysomal translation as one of the major sites of action of LRZ which is independent of changes in body temperature as compared to ethanol and pentobarbital. Since protein synthesis is known to play a key role in learning and memory, the observed inhibitory effects of LRZ may explain its interference with memory consolidation observed under experimental and clinical conditions. PMID- 1598028 TI - Influence of mechanical endothelium removal techniques and conservation conditions on rat aorta responses. AB - Endothelial denudation of aortas induces a lack of relaxation to acetylcholine and enhancement of response to noradrenaline. These modified responses have been studied in rat aorta by using different techniques for mechanical removal of the endothelial layer and maintenance conditions. Rubbing the artery with cotton inside the organ bath preserves the enhancement of response to noradrenaline, and this effect is not present by rubbing the aortas with filter paper outside the organ bath. Both techniques abolished the relaxant response to acetylcholine. The endothelium dependent effects are not observed by conservation of the artery at room temperature during 1 h. The relaxant response to acetylcholine after this period is approximately 29% of the control. These effects were preserved when the conservation temperature was maintained at 4 degrees C and/or the solution was being bubbled with oxygen. PMID- 1598030 TI - [Utilization of antibiotics in Sweden during 1991--a less honourable record]. PMID- 1598029 TI - Effects of alpha-fluoromethylhistidine on locomotor activity, brain histamine and catecholamine contents in rats. AB - One hour after the intraperitoneal (i.p.) injection of FMH (200 mg/kg), locomotor activity and rearing were statistically reduced, by 3 hours later, only the locomotor activity was reduced in rats. The i.p. injection of FMH (100 and 200 mg/kg) had no effects on motor incoordination, blood pressure, heart rate and tetrabenazine-induced ptosis in rats. One and 3 hours after FMH injection, the histamine levels significantly decreased in the hypothalamus, cortex and thalamus, slightly in the olfactory bulb, amygdala, pons-medulla oblongata and midbrain, but very little in the striatum, hippocampus, cerebellum and pituitary. On the other hand, noradrenaline and dopamine levels were not affected in most of the regional parts, although in the cortex and midbrain, the dopamine levels were slightly reduced 1 hour after FMH (100 and 200 mg/kg). These data showed that central histamine may play an important role in the locomotor activity of rats. PMID- 1598031 TI - [High blood pressure and diabetes--important to remind about the changed recommendations]. PMID- 1598032 TI - [Trying new methods in the treatment of anorexia]. PMID- 1598033 TI - [The tick and its region of infection transmission in 1991]. PMID- 1598034 TI - [Geriatric care in Tokyo--a valuable model deserving to be imitated]. PMID- 1598035 TI - [A new method for the treatment of ear catarrh in children]. PMID- 1598036 TI - [Further cases of bone and joint tuberculosis in Stockholm]. PMID- 1598037 TI - [Urinary incontinence--an expensive national disease]. PMID- 1598038 TI - [Are cytokines mediators in the development of insulin-dependent diabetes mellitus?]. PMID- 1598039 TI - [Extracorporeal shockwave lithotripsy in gallstones--an alternative to surgery in selected patients]. PMID- 1598040 TI - [Laser Doppler technique makes measurement of microvascular blood flow changes possible]. PMID- 1598041 TI - [Bjork-Shiley artificial heart valves. Risk estimation points mostly against reoperation. A method for prediction of strut fracture needed]. PMID- 1598042 TI - [The men behind the speculum. A singer's vocal cord played a part in the development]. PMID- 1598043 TI - [Quality of life of elderly patients with essential hypertension can be good]. PMID- 1598044 TI - [Tolvon (mianserin) a second-choice preparation. Watch for blood disorders among the elderly]. PMID- 1598045 TI - [ACE inhibitors should not be administered to pregnant women]. PMID- 1598046 TI - [Alcohol policy decisions to be made before joining the EEC: a liberal alcohol policy could be damaging]. PMID- 1598047 TI - [Why is the frequency of ischemic heart disease increasing in younger Swedish women?]. PMID- 1598048 TI - [Molecular genetic tests are not yet useful for diagnosis of malignant hyperthermia]. PMID- 1598049 TI - [Investigation and treatment of vitamin B 12 deficiency--neurological complications and dementia]. PMID- 1598050 TI - [Medical news are seldom suitable for TV news broadcasting]. PMID- 1598051 TI - [Middle aged men living in the country have lower blood pressure than men living in the cities]. PMID- 1598052 TI - [Morbidity of children in day care centers is not influenced by parental smoking]. PMID- 1598053 TI - [Women should be provided with other leave possibilities during pregnancy than sick-listing]. PMID- 1598054 TI - [Great need of better planning of leave during pregnancy]. PMID- 1598055 TI - [Residual state and mortality justify vaccination of Swedish children against Haemophilus influenzae type b]. PMID- 1598056 TI - [Haemophilus diseases nearly eradicated in Finland]. PMID- 1598057 TI - [100-year anniversary of the Roslagstull hospital. After 100 years of solitude]. PMID- 1598058 TI - [HIV in Scandinavia: Denmark suffers hard but incidence in Finland is remarkably low]. PMID- 1598059 TI - [Population-based preventive work in Olofstrom. Significant predisposition to cardiovascular diseases among Finnish immigrants]. PMID- 1598060 TI - [Quality assurance in psychiatric outpatient care. Information and participation of relatives in the therapeutic programs should be developed]. PMID- 1598061 TI - Losartan, a specific angiotensin II receptor antagonist, increases angiotensin I and angiotensin II release from isolated rat hind legs: evidence for locally regulated renin-angiotensin system in vascular tissue. AB - The effect of Losartan (10(-9) to 10(-6) M) on angiotensins I and II release was examined in isolated hind legs perfused with Krebs-Ringer solution from normal and bilaterally nephrectomized rats. Losartan increased dramatically both angiotensins I (Ang I) and II (Ang II) release in a dose-dependent fashion; the maximal percent increment in Ang I and Ang II release evoked by Losartan (10(-6) M) was about +380% and +160%, respectively, in normal rat hind legs. In nephrectomized animals, Losartan elicited a marked increase in both peptides dose dependently. There was a highly positive correlation between the released amounts of Ang I and that of Ang II altered by Losartan in either normal (r = 0.954) or nephrectomized rats (r = 0.923). These results not only confirm the existence of a functional renin-angiotensin system in vascular tissues, but also suggest that the system is regulated by locally generated Ang II. PMID- 1598063 TI - Osteoarthritis in women: its relationship to estrogen and current trends. AB - With our expanding knowledge of osteoarthritis (OA) over the years, our concept of this "aging" disease has been re-evaluated to that which is the opposite of traditional views. To clinicians and scientists, OA is no longer the inevitable disease of aging, as one conceptualizes gray hair. Epidemiological studies show a higher incidence of OA affecting polyarticular joints in women than age-matched men, particularly those over the age of 55. This discrepancy in sex difference in the OA incidence highlights the significance of sex hormones and their alterations in menopause. Evidence indicates that this alteration possibly occurs early in adult life and may well persist into menopause. As well, this hormonal perturbation is thought to be consequent to obesity in these women. Both in vivo and in vitro studies suggest that estrogen is chondrodestructive via the receptor mediated mechanism. The finding of estrogen receptor in canine, rabbit, and human articular cartilage further confirms this hypothesis. Recent findings of elevated synovial estradiol level and higher estrogen receptor bindings in human osteoarthritic cartilage strongly suggest the importance of local uptake of estradiol (E2) and the possible up-regulation of estrogen receptors. Estrogen, like other hypothesized etiologies, is important in the development of OA in women. PMID- 1598062 TI - An isobolographic analysis of the hypnotic effects of combinations of dexmedetomidine with fentanyl or diazepam in rats. AB - The effects of the combinations of dexmedetomidine-fentanyl and dexmedetomidine diazepam on the righting reflex were studied in rats. The doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. The interactions between dexmedetomidine and fentanyl or diazepam were found to be synergistic. In the dexmedetomidine-diazepam combination studies, less than one-fourth of the single drug dose (for each of two agents) was needed to produce the required effect. These data confirm synergistic interactions between dexmedetomidine and fentanyl or diazepam in producing hypnotic-anesthetic action. PMID- 1598064 TI - Pre- and postnatal stimulation of pulmonary surfactant protein D by in vivo dexamethasone treatment of rats. AB - Fetal (days 18 and 20 of gestation), neonatal (days 0, 2 and 4 of neonate) and adult rats were injected with dexamethasone (1 mg/kg) in vivo and 24 hours later the effect on the contents of surfactant protein D (SP-D) in the rat lungs were examined in comparison with surfactant protein A, disaturated phosphatidylcholine and phosphatidylglycerol. In vivo dexamethasone treatment resulted in significant increases of SP-D content as the other 3 components of surfactant in both fetuses and neonates, but not in adults. Responsiveness to glucocorticoid treatment on SP D content was maximum on day 1 of neonate (2.7 times control value). The contents of surfactant components examined tend to respond better to steroid in postnatal rats. These data demonstrated that glucocorticoid treatment in vivo for short durations exhibits the stimulatory effect on the contents of SP-D in the fetal and neonatal rat lungs. PMID- 1598065 TI - Alteration in the levels of 1,25-(OH)2D3 and corticosterone found in experimental diabetes reduces nerve growth factor (NGF) gene expression in vitro. AB - Circulating concentrations of corticosterone and 1,25-(OH)2D3 have been reported to be respectively increased and decreased in the streptozotocin-treated rats. Using the cell line L929 cultured in a steroid-free medium, we show that the alteration in the levels of corticosterone and 1,25-(OH)2D3 found in vivo in experimental diabetes is able to decrease the synthesis of NGF by these cells. This finding raises a possible relationship between the balance in the concentration of these steroids and some aspects of the neuropathic complications found in experimental diabetes. PMID- 1598067 TI - Chronic variable stress facilitates tumoral growth: reversal by imipramine administration. AB - The present study was conducted to examine whether a chronic variable stress procedure (CVS)--an animal model of depression--facilitates tumor growth, and whether this effect can be modified by concurrent administration of the antidepressant imipramine (IMI). Unstressed rats, with or without previous administration of the immunosuppressive agent cyclosporine (CS), were inoculated with 5 x 10(6) cells of a sarcoma. Another group of rats was inoculated with tumoral cells and later exposed to the CVS procedure with or without concurrent administration of IMI (10 mg/kg, i.p.). An additional group of animals was treated with CS and later given daily injections of IMI (10 mg/kg, i.p.) without stress manipulation. A lack of tumoral development was observed in unstressed animals without previous injections of CS, whereas, prior injections of this immunosuppressive agent increased tumoral growth in unstressed animals. Exposure to the CVS procedure facilitated tumoral growth even in animals without CS injections. This effect was clearly attenuated when chronically stressed rats were concurrently given IMI. These findings support the notion that the development of a tumoral process is facilitated when a state of experimental depression is induced and that the reversal of such a state by antidepressant treatment results in the inhibition of tumor development. PMID- 1598066 TI - Liposomal modification with uronate, which endows liposomes with long circulation in vivo, reduces the uptake of liposomes by J774 cells in vitro. AB - For overcoming rapid removal of liposomes from the bloodstream, we developed reticuloendothelial system (RES)-avoiding liposomes modified with a uronic acid derivative, palmityl-D-glucuronide (PGlcUA). In this current study, we examined the in vitro interaction of PGlcUA-liposomes with J774 cells derived from mouse macrophages. Liposomal association with J774 cells at 37 degrees C did not increase compared with the binding at 4 degrees C when liposomes were modified with PGlcUA. RES-avoiding ability was not specifically endowed by glucuronate but by uronates in general, since palmityl-D-galacturonide showed a similar effect on liposomal clearance in vivo and liposomal uptake in vitro. These facts indicate that modification of the liposomal surface with uronic acid derivatives endows liposomes with a long circulation time in the bloodstream by reducing their uptake by macrophages. PMID- 1598068 TI - Agonist-induced tension determines vascular reactivity during anoxia and reoxygenation. AB - To determine the influence of pre-existing pharmacologically-induced tension on vascular reactivity during anoxia and reoxygenation, rat aortic rings were contracted with norepinephrine, epinephrine, endothelin or KCl to 1, 2 or 4 g of tension. The rings were then exposed to anoxia (95% N2) for 10 min followed by reoxygenation (95% O2). The degree of anoxia-mediated contraction varied with the magnitude of tension before anoxia and resembled the length-tension relationship in myocardial fibers. The optimal agonist-induced tension for maximal anoxic contraction was approximately 1 to 2 g. This relationship between tension and anoxic contraction was observed in all but KCl-contracted rings. The agonist- as well as KCl-contracted rings showed normal relaxant response to acetylcholine, suggesting that a decrease in endothelium-derived relaxing factor (EDRF) alone cannot be the basis of anoxic contraction and release of endothelium-derived constricting factors (EDCFs) may relate to anoxic contraction in agonist preconstricted rings. The relationship between the magnitude of agonist-induced tension and the extent of anoxia-mediated contraction may relate to the ability of endothelium to release EDRF and EDCFs as well as to the degree of phosphorylation in vascular smooth muscle cells. The reoxygenation-mediated contraction was noted to progressively increase in all experiments regardless of the pharmacologic agent used. This increase in reoxygenation-mediated contraction correlated with pre-existing pharmacologic tension, and may relate to calcium influx and restoration of ATP and other mediators in the vascular tissues during reoxygenation. PMID- 1598069 TI - GTP-related effects and binding by differentiating fetal rabbit type II alveolar cells in vitro. AB - Type II alveolar cells were isolated from fetal rabbit lungs and used to determine the effect of GTP-binding protein activation on release of surfactant related material. Cells were prelabelled with [3H]choline for 24 hours. NaF, a G protein activator and GTP gamma S, a nonhydrolysable analogue of GTP, both loaded by hypoosmotic shock treatment, stimulated release of radioactive disaturated phosphatidylcholine. Localization of the cellular binding of [alpha-32P]GTP in fetal type II cells which were induced to differentiate by exposure to fetal lung fibroblast conditioned medium showed that two proteins of apparent molecular weights of 39.6 kd and 17.9 kd bound [alpha-32P]GTP. These proteins were detected only in the cells exposed to the conditioned medium. These results suggest GTP binding proteins are involved in DSPC secretion and differentiation of fetal type II cells is accompanied by changes in GTP binding characteristics. PMID- 1598070 TI - Vitamin B12 accelerates re-entrainment of activity rhythms in rats. AB - The effects of methyl vitamin B12 (5-6 mg/kg, p.o.) on the entrainment of circadian running wheel activity rhythm to a new lighting schedule were measured in rats. After the light-dark (LD) cycle was abruptly reversed, rats given vitamin B12 took less time to entrain their circadian locomotor activity rhythm to the new cycle than did controls. This result indicates that vitamin B12 accelerates the reentrainment of the mammalian circadian activity rhythm following an abrupt change in the environmental LD cycle. PMID- 1598071 TI - Quantitative determination of pertussis toxin-sensitive G proteins using [32P]ADP ribosylation in human platelet membranes: negative correlation with ages. AB - The optimum condition to quantitate the [32P]ADP-ribosylation catalyzed by pertussis toxin (islet-activating protein, IAP) in human platelet membranes was investigated. Autoradiography indicated the incorporation of 32P into the band corresponding to the molecular weight of 40-41 kDa, which was augmented by the addition of GTP in the presence of 10 mM MgCl2. On the other hand, non hydrolyzable GTP analogue, guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) enhanced the IAP-catalyzed [32P]ADP-ribosylation only in the absence of MgCl2. The amounts of IAP-catalyzed [32P]ADP-ribosylation in the presence of 100 microM GTP and 10 mM MgCl2 were linear in proportion to the protein concentrations within the limited range of protein concentrations, indicating that this simple quantitative method could be adequately used to evaluate the IAP-sensitive G proteins. Data from fifteen healthy volunteers (7 males and 8 females ranging 24 to 60 years old) indicate that the amounts of IAP-sensitive G proteins in platelet membranes are significantly negatively correlated with ages. PMID- 1598073 TI - Contrasting effects of misoprostol on systemic and intrapulmonary lipopolysaccharide-induced tumor necrosis factor-alpha. AB - Tumor necrosis factor-alpha (TNF), a cytokine produced by mononuclear phagocytes in response to lipopolysaccharide stimulation, is a potent mediator of the inflammatory cascade. However, the immunomodulatory signals regulating TNF expression in the host are poorly defined. Recently, metabolites of the prostaglandin E series have been shown to inhibit TNF production in vitro. In order to determine if PGE1 alters TNF activity in vivo, rats were given misoprostol, a synthetic PGE1 analogue, or saline by gavage and subsequently challenged with either intravenous or intratracheal Escherichia coli lipopolysaccharide. These in vivo data show that PGE1 is a potent inhibitor of TNF production by systemic mononuclear phagocytes. In contrast, alveolar macrophages appear to be refractory to misoprostol's suppressive effects on LPS induced TNF. This study supports in vitro observations that mononuclear phagocytes within different compartments exhibit differential responsiveness to immunomodulators. PMID- 1598072 TI - Production and characterization of an iminoimidazolidine specific monoclonal antibody using para-aminoclonidine as antigen. AB - Para-aminoclonidine coupled to hemocyanin was used to produce mouse monoclonal antibodies directed against clonidine. The properties of one of these, called mFE7, secreted by a clone of hybrid myeloma, are described. This antibody displayed total crossreactivity with imidazolidines and no crossreactivity at all with catecholamines or other known naturally occurring substances tested. A liquid phase radioimmunoassay permitted the detection of immunoreactivity in human brain extracts. The mFE7 antibody could be useful for immunopurifying the endogenous ligand of Imidazolines Preferring Receptors (IPR) which are catecholamines insensitive. PMID- 1598074 TI - Presence of methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinolines, derivatives of the neurotoxin isoquinoline, in parkinsonian lumbar CSF. AB - The TIQ derivatives 2-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (2 MDTIQ) and 1-methyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (1-MDTIQ, salsolinol) were identified the first time as possible endogenous neurotoxins in parkinsonian but not in normal human lumbar cerebrospinal fluid by high performance liquid chromatography with electrochemical detection. Additionally, MDTIQ analogues were incubated with a monoamine oxidase (MAO) assay. MAO was able to metabolize dose-dependently 2-MDTIQ, whereas 1-MDTIQ was not modified by the enzyme. PMID- 1598075 TI - Changes in lipid peroxide levels and activity of reactive oxygen scavenging enzymes in skin, serum and liver following UVB irradiation in mice. AB - The effect of acute UVB on the generation of reactive oxygen species (ROS) in the skin and the induction of ROS scavenging enzymes in situ was examined. Lipid peroxide levels and the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and D-glucose-6-phosphate dehydrogenase (G-6-P-D) were determined in the skin, serum, and liver of ICR mice subjected to 1400 mJ/cm2 of acute UVB irradiation. In irradiated skin, lipid peroxides were increased at 3 and 24 hr after irradiation, whereas the four ROS scavenging enzymes were generally decreased during the first 48 hr after irradiation. In the serum, lipid peroxides showed an increase at 3 hr, but enzyme activities remained negligible. In the liver, lipid peroxides showed similar behaviour to that in skin. GSH-Px activity in the liver was decreased during the first 24 hr, whereas G-6-P-D showed substantial fluctuation and SOD and catalase activities showed no change. These data are consistent with a model in which lipid peroxides generated in the UVB-irradiated lesions are transported to the liver and there metabolized by the scavenging enzymes induced in situ. PMID- 1598077 TI - Clara Barton. PMID- 1598076 TI - Plasma lipoproteins and cholesterol metabolism in Yoshida rats: an animal model of spontaneous hyperlipemia. AB - The purpose of this study was to characterize the lipoprotein profile and cholesterol metabolism in Yoshida rats, a strain of inbred genetically hyperlipemic animals. For comparison, Brown Norway rats were used as control animals. Plasma cholesterol and triglycerides were higher in Yoshida as compared to Brown Norway, the elevation of cholesterol being due to a rise in HDL fraction. Triglyceride distribution among lipoproteins showed an increase in VLDL fraction. Hyperlipemia was not related to diabetes, hypothyroidism or nephropathy. Plasma triglycerides production was increased in Yoshida rats, while lipoprotein and hepatic lipases were similar in the two groups. Hypercholesterolemia was associated with a defect of lipoprotein receptor activity and with elevated HMG-CoA reductase and cholesterol 7 alpha - hydroxylase; conversely ACAT activity was lower in Yoshida as compared to Brown Norway rats. Sterol fecal excretion was comparable in the two groups and hypercholesterolemia in Yoshida rats was not associated to an increase of cholesterol saturation of the bile. We suggest that lipoprotein overproduction is the main cause for hyperlipidemia in this strain of rats. PMID- 1598079 TI - Microsurgery as an aid to middle cerebral artery endarterectomy. AB - 1. Instrumentation and technique for microsurgical reconstruction of small arteries are described. 2. Two cases are reported in each of which an obstruction was removed from the middle cerebral artery for early hemiplegia. 3. The work presented is of a preliminary nature. No conclusions can be drawn as to ultimate value. Further clinical trial seems justified. PMID- 1598078 TI - Looking back, going forward. PMID- 1598080 TI - New method of surgical treatment of blood vessel lesions. AB - Professor Androsov's articles should be of considerable interest to American surgeons, representing as they do a new freedom in the exchange of ideas with the medical profession of the Soviet Union. In recent years no Russian surgeon has sought publication of original work in surgical journals of this country. Early last fall I visited Professor Androsov in Moscow at the Sklifosovsky Institute, a hospital made famous by the late Professor Yudin. I was impressed by the work that he and his associates were doing in peripheral vascular surgery and in the reconstruction of lye burns of the esophagus. Professor Androsov was extremely hospitable and showed a keen interest in the freer exchange of knowledge between American and Soviet surgeons. He and his staff evinced a friendly interest in American medical institutions as a result of Professor Yudin's visit to the Mayo Clinic and other institutions in this country in former years. Let us hope that other Soviet surgeons will follow Professor Androsov's lead in submitting to us from time to time reports of their work. PMID- 1598081 TI - Surgical technique for combined liver/intestine transplantation in rats. AB - Simultaneous liver transplantation may reduce the risk of intestinal transplant rejection. We have recently developed two new models of combined liver/intestine transplantation (LIT) in the rat to study this phenomenon. Herein, we report our experience with LIT using a single donor (SD) or multiple donors (MD). Large volumes of fluid were required to prevent a drop in the mean arterial pressure during the anhepatic phase in the SD recipients. Many of the SD recipients died of intraoperative hypovolemic shock (57%). The MD recipients had a shorter anhepatic time (12 +/- 1 minutes vs. 17 +/- 2 minutes; P less than 0.01) and a shorter warm intestinal ischemia time (15 +/- 1 minutes vs. 32 +/- 2 minutes; P less than 0.01). Operative mortality rates were much lower in the MD recipients (10% vs. 68%; P less than 0.01). The long-term survival rate using MD was 71% at 1 month. Graft function was normal in the long-term survivors. LIT with MD provides a good model to study the immunological effects of multivisceral grafting. PMID- 1598082 TI - Metabolic effect of pancreaticoduodenal transplantation in diabetic rats. AB - Outbred Wistar rats were randomly assigned to three experimental groups: GI, 10 nondiabetic control rats; GII, 10 alloxan-diabetic control rats; GIII, 25 alloxan diabetic rats that received pancreaticoduodenal transplantation (PDT) from normal donor Wistar rats and were immunosuppressed with cyclosporin A. For 7 prior and 4, 7, 14, 21, and 30 days posttransplantation (during which the animals were housed in metabolic cages for periods of 24 hours) body weight, water and food intake, urine output, blood and urinary glucose, plasma insulin, and glucagon were recorded. These parameters were also concurrently recorded for diabetic and nondiabetic control rats. Animals were sacrificed after 30 days and histological and immunohistochemical studies of the pancreas were performed. Pancreatic transplants consistently and significantly improved the metabolic abnormalities of the diabetic rat (P less than 0.01) by restoring body weight gain, and by immediate relief of hyperglycemia, glucosuria, polyuria, polydipsia, and also the low levels of plasma insulin. The plasma glucagon, elevated in diabetic control rats, did not change after transplant. PMID- 1598083 TI - The effect of venous flow alterations upon patency of rat femoral vein anastomoses. AB - The rat femoral vein has become a standard model for laboratory training in microvascular anastomotic technique as well as for research investigations into factors affecting venous patency. This study examined the short-term patency (1 and 7 days) of rat vein anastomoses. The influences upon patency of epigastric flap creation and distal femoral vessel ligation (epigastric flow only) were explored. In a separate experiment, blood flow from the femoral vein was determined through catheter collection of venous efflux; the influences of island epigastric flap creation and distal femoral ligation on flow rates were explored. It was found that 82% of basic femoral vein anastomoses were patent at one day, while 100% of anastomoses associated with an epigastric flap and ligated/transected distal femoral vessel circulation (creating a low-tension anastomosis) were patent (P less than 0.01). With distal femoral vessel ligation and no transection (normal tension at the repair), anastomoses were patent in 90% of the veins when an epigastric flap was also raised, and in 60% when a flap was not created. When a flap was raised without disturbing the distal femoral circulation, vein patency was 75% at one day. When the vein anastomosis was performed with distal femoral vein ligation, the patency rate was 50%. All veins patent at 1 day were also patent at 7 days post-op; 96% of veins clotted at 1 day were found to be patent at 7 days. The venous efflux was not found to vary significantly when an epigastric flap was raised.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598084 TI - Formation of endovasal structures and intramural channels in rat vena cava after application of microsurgical suture: prophylactic effect of heparin and trental administration. AB - The study addresses the histopathology of end-to-end microanastomosis in the rat inferior vena cava. The vessels were harvested in 4 hours and 1, 3, 7, 14, and 30 days after the operation and were evaluated using light, scanning, and transmission electron microscopy. The endothelium was completely restored within 7 days after the surgical procedure. Endovasal structures at the microsuture site and intramural endothelial channels opening into the vena cava lumen developed as a result of endothelialization and parallel substitution of the three-dimensional fibrin framework of the mural microthrombus with connective tissue. By 1 month, aggregates of platelets, fibrin, and adhering leukocytes were observed in the intramural channel mouths. Administration of heparin and Trental for 1 week after the operation reduced the number of intramural channels and prevented the formation of endovasal structures at the site of microvenous anastomosis. PMID- 1598085 TI - Enhancement of motor nerve regeneration by nerve growth factor. AB - The sciatic nerves of adult Wistar rats were severed bilaterally. Each nerve was sutured into a silicone tube used as a conduit, leaving a 5 mm gap in length between the nerve ends. Nerve growth factor in a saline solution vehicle was injected into the silicone chamber on the right side and normal saline solution (control) on the left. Six weeks after surgery, electrophysiological studies were performed. The motor nerve conduction velocities (MNCV) were significantly increased in the NGF-treated nerves. In one rat, the MNCV on the NGF-treated side was 66.6 m/s, in the range of normal nerves. There was no significant difference between the two sides in the amplitudes of evoked muscle action potentials. There are apparently no reports on the effect of NGF on motor neuron regeneration in vitro. In this study, NGF was found to enhance motor nerve regeneration. PMID- 1598087 TI - Maternal mortality. PMID- 1598086 TI - Replantation of an amputated upper lip. AB - Soft tissue defects of the face are a difficult reconstructive problem. Replantation of large amputated segments of the face has been rarely successful and has lagged well behind extremity trauma due in part to the relative rarity of these defects. Presented is a case of successful microvascular replantation of half of the upper lip after a dog bite. PMID- 1598088 TI - Research in midwifery: are midwives their own worst enemies? AB - This study investigated the hypothesis that midwives will undervalue research they believed to have been undertaken by a midwife as compared with that believed to have been undertaken by an obstetrician. Eighteen midwives were asked to assess two comparable research articles on 5 criteria. Half the sample were informed that the first article was written by a midwife and the second by an obstetrician. The order of authorship was reversed for the remainder of the sample. A related t-test was carried out to compare the midwife's paper with the obstetrician's on each of the 5 criteria. These suggested that no difference was perceived between the midwife's and obstetrician's clarity of expression or expertise on the topic in question, but significant differences were found on attributed grasp of research methodology, understanding of statistical analysis and contribution to current understanding, with the midwife emerging worse on all three (t = 1.99, p less than 0.05, t = 2.28, p less than 0.025, t = 1.8, p less than 0.05 respectively). Comparison of the overall scores also revealed that the general quality of the midwife's paper was also perceived to be poorer than the obstetrician's (t = 2.24, p less than 0.025). The findings are partially explained in terms of the gender influences that operate in midwifery. PMID- 1598089 TI - The effects of smoking in pregnancy: a review of approaches to behavioural change. AB - A substantial body of evidence has now been accumulated which suggests that cigarette smoking during pregnancy can result in an increased incidence in the number of babies born of lower birth weight. There is also an increase in perinatal mortality in babies born to smoking mothers, as well as a higher incidence of spontaneous abortion, greater mortality and morbidity during the first year of life and a lower rate of growth and reduction in mental aptitude into late adolescence. Despite this compelling evidence it has been found that only a relatively small proportion of women who smoke actually stop when they become pregnant. It has been found that knowledge of the potential effects of smoking does not appear to exert a major influence on pregnant women's smoking behaviour. There is also relatively little research which addresses the reasons why some pregnant women continue to smoke during pregnancy. The issue is clearly complex and the evidence that does exist points to the need for health professionals to adopt more sophisticated interventions with pregnant women, which move beyond a simple educational approach. PMID- 1598090 TI - Obstructed labour: its contribution to maternal mortality. AB - Every year 85,000 women die from obstructed labour and many many more lose their baby and have debilitating physical damage as a result. In this paper the extent of the problem is described. Methods by which obstructed labour can be prevented are given. Early detection and prompt referral for appropriate treatment are vital if damage is to be minimised. This requires particular attention in midwifery education which must include community experience which fosters dialogue and strengthens prevention. This paper is based on one originally given at the ICM/WHO/UNICEF pre-congress workshop in Kobe, Japan, October 1990. PMID- 1598091 TI - Scoring and setting pass/fail standards for an essay certification examination in nurse-midwifery. AB - Examination for certification or licensure of health professionals (credentialing) in the United States is almost exclusively of the multiple choice format. The certification examination for entry into the practice of the profession of nurse-midwifery has, however, used a modified essay format throughout its twenty-year history. The examination has recently undergone a revision in the method for score interpretation and for pass/fail decision making. The revised method, described in this paper, has important implications for all health professional credentialing agencies which use modified essay, oral or practical methods of competency assessment. This paper describes criterion referenced scoring, the process of constructing the essay items, the methods for assuring validity and reliability for the examination, and the manner of standard setting. In addition, two alternative methods for increasing the validity of the pass/fail decision are evaluated, and the rationale for decision-making about marginal candidates is described. PMID- 1598092 TI - Abortion: its contribution to maternal mortality. AB - Every year between 100,000 and 200,000 women die from illicit abortion. In this paper the magnitude of the problem is described, those most at risk are identified and methods of preventing unwanted pregnancy are suggested. It is argued that midwives have a major role to play in family planning counselling and the provision of contraceptive services. Midwives can also reduce maternal mortality by resuscitating women when emergencies arise from incomplete abortion. This paper is based on one originally given at the ICM/WHO/UNICEF pre-congress workshop is Kobe, Japan, October 1990. PMID- 1598094 TI - Increased safety-belt use--United States, 1991. AB - From 1980 to 1990, safety-belt use among passenger-vehicle drivers in the United States increased from 11% to 49%; in 1990, use of safety belts prevented approximately 4800 deaths and 120,000 serious injuries among front-seat occupants (1). The increased use of safety belts from 1984 through 1990 was associated primarily with the enactment of state laws (Figure 1). In recent years, however, the rate of increase in use has declined. To increase safety-belt and child passenger restraint use in the United States, in February 1991, the National Highway Traffic Safety Administration (NHTSA) initiated the "70% by '92" program to increase safety-belt use to 70% by the end of 1992 through emphasis on enforcement efforts combined with public awareness campaigns. This report summarizes an assessment of the impact of the program through 1991. PMID- 1598093 TI - Selected tobacco-use behaviors and dietary patterns among high school students- United States, 1991. AB - In the United States, 30% of all cancer deaths and 87% of lung cancer deaths are attributable to tobacco use (1); approximately 35% of all cancer deaths are associated with diet (2). Because tobacco-use behaviors and dietary patterns (particularly diets high in fat and low in fruits, vegetables, and grains) established during youth may extend into adulthood and may increase the risk for cancer and other chronic diseases, these behaviors should be monitored and addressed among youth (1,3). This article presents self-reported data on the prevalence of selected tobacco-use behaviors and dietary patterns associated with risk for cancer and other chronic diseases among U.S. students in grades 9-12 during 1991. PMID- 1598095 TI - Role of alcohol in forensic deaths--Westchester County, New York, 1989. AB - In the United States, 58% of all adults consume alcohol, and death rates for most injuries and some diseases increase directly in relation to levels of consumption (1-3). Forensic deaths (i.e., deaths certified under the medical examiner system) include a substantial proportion of cases for which alcohol use may have contributed to the death; in many cases, this system provides detailed medical information on causes of death because of autopsies and blood alcohol level testing. To further characterize alcohol-related deaths in Westchester County (4,5), the New York Medical College (NYMC) and the Westchester County Department of Laboratories and Research (WCDLR) estimated the total alcohol-related mortality (ARM) and years of potential life lost before age 65 (YPLL) for all deaths certified by the medical examiner for Westchester County, New York, during 1989. This report summarizes the findings and addresses public health applications for estimating ARM employing this method. PMID- 1598097 TI - Brief report: a deficiency of carnitine-acylcarnitine translocase in the inner mitochondrial membrane. PMID- 1598096 TI - The risk of stroke in patients with acute myocardial infarction after thrombolytic and antithrombotic treatment. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico II (GISSI-2), and The International Study Group. AB - BACKGROUND: Many trials in patients with acute myocardial infarction have demonstrated that thrombolytic therapy is not associated with an excessive risk of stroke, as compared with conventional treatment. However, the incidence of various forms of stroke in patients treated with different thrombolytic and antithrombotic regimens and the associated effect of risk factors for stroke are largely unknown. METHODS: Strokes occurring in patients hospitalized with acute myocardial infarction who were enrolled in either of two large trials were analyzed. The patients were randomly assigned to receive streptokinase (1.5 million units) or recombinant tissue plasminogen activator (t-PA) (100 mg) and also randomly assigned to receive subcutaneous heparin or no heparin. Ninety-one percent of the patients also received aspirin. RESULTS: Complete data were available on 20,768 patients. A total of 236 (1.14 percent) had strokes in the hospital; 0.36 percent had hemorrhagic strokes, 0.48 percent ischemic strokes, and 0.30 percent strokes of undefined cause. Patients treated with t-PA had a small but significant excess of stroke as compared with those who received streptokinase (1.33 vs. 0.94 percent; adjusted odds ratio, 1.42; 95 percent confidence interval, 1.09 to 1.84). The administration of subcutaneous heparin in addition to a thrombolytic agent did not increase the risk of stroke (risk with heparin, 1.13 percent; without heparin, 1.14 percent). Older age, a higher Killip class, and the occurrence of anterior infarction significantly increased the risk of stroke, whereas a higher body-mass index or a history of hypertension, diabetes, or smoking did not. CONCLUSIONS: Patients with acute myocardial infarction who receive thrombolytic therapy have a small risk of stroke. Treatment with t-PA as compared with streptokinase resulted in a small but significant excess of stroke. Subcutaneous heparin, given together with t-PA or streptokinase and aspirin, did not result in an increased risk of stroke. PMID- 1598098 TI - Brief report: renal tubular acidosis in carnitine palmitoyltransferase type 1 deficiency. PMID- 1598099 TI - Failure to resolve a diagnostic inconsistency. PMID- 1598100 TI - Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 27-1992. A 20-year-old man with recent intermittent abdominal pain, constipation, and diarrhea. PMID- 1598101 TI - Thrombolytic therapy for elderly patients. PMID- 1598102 TI - More on SI units. PMID- 1598103 TI - More on SI units. PMID- 1598104 TI - More on SI units. PMID- 1598105 TI - More on SI units. PMID- 1598106 TI - More on SI units. PMID- 1598107 TI - More on SI units. PMID- 1598108 TI - More on SI units. PMID- 1598109 TI - Lipid levels and "affluent" diets. PMID- 1598110 TI - Lipid levels and "affluent" diets. PMID- 1598111 TI - Lipid levels and "affluent" diet. PMID- 1598112 TI - Lipid levels and "affluent" diet. PMID- 1598113 TI - How far to lower blood pressure. PMID- 1598114 TI - Lethal neonatal deficiency of carnitine palmitoyltransferase 2. PMID- 1598116 TI - Second thoughts. PMID- 1598115 TI - Efforts to address the problem of physician self-referral. PMID- 1598118 TI - [Rearrangements of efferent activity parameters in generators of cyclic motor reactions during electric stimulation of cerebellum inputs and outputs in the cat]. AB - Rearrangements of the activity parameters of scratching and locomotor generators conditioned by electric stimulation of the inferior olive, nucleus reticularis lateralis as well as of the fastigial nucleus and nucleus interpositus of the cerebellum were investigated on decerebrate immobilized animals. Scratching and locomotor generators were characterized by the ability to effectively rearrange the time structure of their activity in response to certain changes in phase and amplitude characteristics of signals arriving both by the mossy and climbing inputs of the cerebellum. The flexor half-centre of the locomotor generator and aiming half-centre of the scratching generator increased both the period and intensity of their activity under influence of signals arriving to the cerebellum from the inferior olive and nucleus reticularis lateralis at the first half of the working phase of these half-centres. Stimulation of the inferior olive and nucleus reticularis lateralis during the second half of the flexor and aiming phases evoked somewhat different changes in correlation of activity for half centres of the locomotor and scratching generators. A slight shortening of the activity period of the aiming half-centre during scratching and a decrease of the activity period of the extensor half-centre during locomotion were observed. Stimulation of the structures mentioned above during the working phase of half centres controlling limb extensor movements evoked shortening of the extensor half-centres activity period during locomotion and exerted no effect on the scratching jerk half-centre activity period during scratching. The scratching generator, unlike the locomotor generator is characterized by a significant degree of resemblance of the rearrangement of generator efferent activity parameters evoked by electric stimulation of the cerebellum nuclei and its afferent inputs. Possible mechanisms of forming the correcting influences on scratching and locomotor generators from the cerebellum during changes in phase and amplitude characteristics of its input signals are discussed. PMID- 1598117 TI - Cost effectiveness of thrombolytic therapy with streptokinase in elderly patients with suspected acute myocardial infarction. AB - BACKGROUND: There is a lack of consensus among cardiologists about the potential benefit of thrombolytic therapy for suspected acute myocardial infarction in older patients. To investigate this issue, we constructed a decision-analytic model for patients 75 years of age or older who present with ST-segment elevation within six hours of the onset of symptoms suggesting acute myocardial infarction. METHODS: The variables incorporated in this model were the probability that the patient has an acute myocardial infarction, the probability of in-hospital death among patients with acute myocardial infarction who do not receive thrombolytic therapy, the probability of a fatal or incapacitating complication resulting from thrombolytic therapy, and the expected relative reduction in the risk of death associated with thrombolytic therapy in patients with acute myocardial infarction. Our analyses were based primarily on the use of streptokinase as the thrombolytic agent. RESULTS: Given our base-line assumptions, the probability of dying in the hospital was 21.4 percent if thrombolytic therapy was given and 24.4 percent if it was not given. In one-way sensitivity analyses, thrombolytic therapy decreased the risk of dying if the probability that the patient had an acute myocardial infarction was assumed to be greater than 9 percent, if the probability of dying in the hospital after an acute myocardial infarction without thrombolytic therapy was assumed to be greater than 3 percent, if the rate of fatal or incapacitating complications due to thrombolytic therapy was assumed to be 4 percent or less, or if the relative reduction in the risk of death associated with thrombolytic therapy was assumed to be greater than 1 percent. On the basis of our base-line assumptions, our estimate of the cost effectiveness of streptokinase therapy (the cost per year of life saved) for an 80-year-old patient with suspected acute myocardial infarction was $21,200. For a wide range of assumptions about risks, benefits, and costs, the cost per year of life saved remained less than $55,000. CONCLUSIONS: Within the limitations imposed by the assumptions used in our analysis, thrombolytic therapy with streptokinase was found to be a beneficial and cost-effective treatment for suspected acute myocardial infarction in elderly patients in a wide variety of clinical circumstances. PMID- 1598119 TI - [Code models of sensory information from the skin analyzer periphery]. AB - Experimental studies on the relations between the afferent flows in A-beta and A delta and C-fibres of a cutaneous nerve for different stimulations of cutaneous receptors provided the basis for modelling of various digital and graphical codes of the known and unknown sensations. PMID- 1598120 TI - [Influence of ethanol on the background activity of neurons in the lateral vestibular nucleus of the cat]. AB - Single intravenous administration of ethanol (1 g/kg) to experimental cats influences 95% of investigated neurons of the lateral vestibular nucleus. In most (56.5%) neurons possessing primarily high-frequency background activity of the uninterrupted arrhythmic type ethanol administration has caused a decrease in the impulsation frequency by 84-93%; 14.5% neurons of the burst-group activity demonstrate a primary distinct increase of the average frequency of discharges, prolongation of bursts and the numbers of impulses in them changed 20-30 min after ethanol administration by sharp inhibition of the background activity up to its complete ceasing. A distinct exciting effect has arisen due to the ethanol effect during the whole period of observation in 23.6% of neurons mostly with primary low frequency of the background activity. The rehabilitation of the activity up to the primary level as a rule did not appear even 90 min later. Repeated administration of ethanol in the same dose has induced a cumulative effect. PMID- 1598121 TI - [Effect of penicillin on the synaptic activity of isolated spinal cord motor neurons in the lamprey]. AB - Penicillin (PCN) has been studied for its effect on the membrane potential (MP) and synaptic activity of lamprey spinal cord motoneurons using intracellular recording in the in vitro spinal cord-notochord preparation. In one group of motoneurons with relative low MP (58.7 +/- 5.2 mV, n = 28) PCN induced depolarization, enhancement and prolongation (up to 80-220%) of the initial amplitude of excitatory postsynaptic potentials (EPSPs) evoked by the stimulation of dorsal roots spinal tracts. If the MPs (in the other group of motoneurons) were high (70.0 +/- 5.7 mV, n = 20) depolarization was not observed and the potentiation of EPSPs did not exceed 25-70% of the initial value. These effects of PCN can be eliminated by a preliminary addition of excitatory or inhibitory amino acid antagonists in the superfusion solution. The obtained results allow suggesting the presence of two different acceptor sites for PCN in membranes of lamprey spinal cord motoneurons. PMID- 1598122 TI - [Role of direct and feedback inhibition in the effect of "priming" in hippocampus slices]. AB - Field potentials (FP) were recorded from radial and pyramidal layers of the mice hippocampus after conditioning and testing stimulations of the Schaffer collaterals. The effect of a preliminary conditioning stimulus on the tested responses (the "priming" effect) was studied for different testing intensities and interstimulus intervals of 50 to 5000 ms. Two series of experiments were conducted. In the first series the influence of the conditioning stimulus delivered with the interval of 200 ms on the testing stimuli of various intensities was studied. The duration of the testing FP in the radial layer was measured. The plot of the FP duration against the stimulus strength revealed three regions. For the first region (at small stimulus intensities) the FP duration was maximal and independent on the stimulus intensities. The second region began at the point where FP duration reduced presumably due to the feed forward inhibition. The conditioning stimulus caused a widening (recovery) of the FP due to suppression of the inhibition. In the third region the stimulus intensity was sufficient to excite pyramidal cells and therefore to activate the feed-back inhibition. The time course of the FP was contaminated by the population spike and FP duration became inadequate for the evaluation of the "priming" effect. The second set of the experiments was aimed to study possible changes in the feed-back inhibition. With this end in view the influence of the conditioning (priming) procedure on the paired-pulse depression was studied. The main effect of the conditioning was a suppression of the paired-pulse depression, i.e. a suppression of the feed-back inhibition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598123 TI - [Role of the frontal cortex in the organization of rapid ballistic movements of rats]. AB - Rapid ballistic food-getting movement characteristics were studied in albino rats. After ablation of the second area of the frontal cortex contralaterally as to the preferred extremity the number of attempts increased and their duration with reorganization of the phase structure of movements decreased. The habit of food extraction was lost after bilateral ablation of the cortex. The obtained results have illustrated significance of the frontal cortex in formation and realization of moving programmes. PMID- 1598124 TI - [Changes in the responsive ability of parietal associative cortex neurons to stimulation of associative thalamic nuclei during development of inhibition]. AB - Neuronal responses of area 7 of the parietal associative cortex (PAC) to paired stimulation of the nLD and nLP thalamic nuclei were investigated by extra- and intracellular recording methods. It was found out that testing stimulation of the associative nuclei resulted in inhibition, facilitation or absence of clear neuronal responses. Inhibition was observed more often then other types of reactions. The intracellular recording has shown that inhibition of responses to testing stimuli developed during the initial phase of IPSP, while in the repolarization phase a facilitation was possible. The reversion of a Cl- dependent component of IPSP did not lead to inhibition of responses to the testing stimulation in that period. It is suggested that inhibition of responses to the testing stimulus occurs in the presence of inward Cl- -dependent current, while facilitation of responses may be a result of activation of the late EPSPs. PMID- 1598125 TI - [Variability of interspike intervals of human motor neurons during voluntary muscle contraction and tonic vibration reflex]. AB - Firing of motor units of human soleus, triceps brachii and rectus femoris muscles was studied. Standard deviations of interspike intervals against mean intervals were plotted during voluntary muscle contraction and tonic vibration reflex. There was no significant difference between the results obtained under these conditions. PMID- 1598126 TI - [Organization of vestibulospinal systems in vertebrates]. AB - The data about vestibular nuclear complex and vestibulospinal systems in the submammalian and mammalian vertebrates are offered in the review. Information presented in the world literature concerning the vestibular nuclei topography, structure, fibre connections and influences on the spinal cord and skeletal muscles is summarized. The current conceptions of the structural and functional specificity of different vestibulospinal systems are considered. PMID- 1598127 TI - [Histological diagnosis of brain tumors: (21). Glioblastoma]. PMID- 1598128 TI - [Neuropsychological test]. PMID- 1598129 TI - [The hemodynamics of intracranial aneurysm by transcranial Doppler arteriography]. AB - The use of an ultrasonic transcranial Doppler arteriography (TCDA) technique for noninvasive diagnosis of cerebral aneurysm is described. Twenty one patients with intracranial aneurysm previously diagnosed by conventional angiography were evaluated with Trans-Scan (EME). Mapping image was used as a guide to identify parent artery and aneurysm. In four patients, we could not record aneurysmal blood flow because of their poor or non existent acoustic window. Good images were recorded in 17 patients. The location of aneurysms were A-com (1 case), Distal ACA (2 cases), IC (7 cases), MCA (3 cases), Basilar (1 case) and IC fusiform (3 cases). Two types of Doppler spectra were obtained from the aneurysmal blood flow. One was characterized by a high density zone along the base line and the other was characterized by a homogeneous high density zone. In both types, Doppler sound was characterized by low frequency sound. The low frequency sound reflects the turbulent flow in the aneurysm. The pattern of Doppler spectra obtained from ordinary arteries was characterized by a high density zone along the descending limb of the envelope. Doppler sound is characterized by high frequency sound. A homogeneous spectral pattern was obtained in both aneurysms and ordinary arteries. But it was possible to differentiate them by Doppler sound. Consequently to be able to hear Doppler sound is very important. We were able to detect fourteen of seventeen aneurysms (A-com 1/1, Distal ACA 1/2, IC 7/7, MCA 2/3, Basilar 1/1, and IC fusiform 2/3). The rate of detection was 82 percent. Aneurysm size ranged from 5mm x 4mm to 16mm x 18mm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598130 TI - [Basic research for interferon gene therapy against malignant glioma]. AB - In order to establish new interferon therapy against malignant glioma by selective transfection of its gene, we developed a novel transfection system using liposomes bearing positive charges on their surface and entrapping plasmids containing the HuIFN- beta gene (pSV2IFN-beta). The liposomes were composed of N (alpha -trimethylammonioacetyl) -didodecyl-D-glutamate chloride (TMAG), dilauroylphosphatidylcholine (DLPC), and dioleoylphosphatidylethanolamine (DOPE) as a molar ratio of 1:2:3. The liposomes were not observed to have cytotoxicity for human glioma cells, when applied at a rate less than 15nmol/ml. This liposome mediated transfection of the gene into the cultured glioma cells (U-251-MG) resulted in the secretion of HuIFN- beta into the medium. The HuIFN- beta level in the culture media of glioma cells reached 23 IU/ml after 96h of incubation. When the pSV2IFN-beta containing liposomes were coupled with a monoclonal antibody (G-22 MCA) against glioma-associated antigen (G-22), the level of HuIFN beta in the medium was 181 IU/ml, resulting in a 7-fold increase. It was indicated that this transfection system was a safe and selective method in the case of TMAG/DLPC/DOPE liposomes. PMID- 1598131 TI - [Surgical treatment of aged patients with ruptured cerebral aneurysm; evaluation of the operations performed without using retractors]. AB - Sixteen patients over 70 years of age with ruptured cerebral aneurysms in the anterior circulation were surgically treated via the pterional approach. Self retaining brain retractors (SRBRs) were used in seven patients (Group A), but not in nine other patients (Group B). On admission there were no significant differences between the groups in terms of the neurological grading of Hunt & Kosnik or the CT grading of Fisher. The timing of the operation was decided on the basis of the neurological grading of Hunt & Kosnik and the systemic complications present in each case. Early operation (within 2 days) was performed in 10 cases (5 cases in each group), whereas delayed operation (after 15 days) was carried out in 6 cases (Group A: 2 cases; Group B: 4 cases). Symptomatic vasospasm occurred in 43% of Group A and in 33% of Group B. Postoperative CT scans showed new or aggravated brain edema in the fronto-temporal region (the site of craniotomy) in 3 Group A cases, but not in any Group B cases. By means of technetium-99m-labeled hexamethyl-propyleneamine oxime single photon emission computed tomography (SPECT) the regional cerebral blood flow (CBF) in the fronto temporal region of the operated side was studied in 6 patients (3 cases in each group) one day after and three months after the operation. One day after the operation, the regional CBF in the fronto-temporal region had decreased in the three Group A cases, but no changes were observed in the three Group B cases. Three months after the operation the regional CBF impairment had improved in 2 of the Group A cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598132 TI - [Three dimensional display of cerebral vessels using a personal computer]. AB - A new method for a 3-D reconstruction of angiographic cerebral vessels was developed. This system was constructed from inexpensive equipment such as a personal computer, a video camera, a video display, and a digitizer. The input of the vessel images on anteroposterior and lateral angiograms was performed using a video camera with a personal computer and an image processing program (FDM 98-4; Fotoron Co.). These processed images were modified with our original editorial method. This can contribute a lot to the erasing of "non-vessel" images such as skull bone and other noise. It also adds concerning vessels which cannot be clearly taken from angiograms with the video camera. The most beneficial point of the editorial method was to reduce the time consumed in the reconstruction. The spatial points of X-ray discharging boxes against the AP and lateral films were calculated from the length and width of the radiated images of metal bars. These bars were attached to the 3 planes of the lucent box in which the patient's head was inserted to take the angiograms. The 3-D points of the vessels were calculated as follows; one point of a vessel on the lateral image and the spatial point of the X-ray discharging box against the image were linked by a line on which a point moved within a Z range. When the extended line which linked the point and the position of the X-ray discharging box against the AP view crossed the AP image, the Z value of the point was adopted and X and Y values were gained.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598133 TI - [Significance of the cerebral venous system in the development of DIND in subarachnoid hemorrhage]. AB - The significance of superficial venous system in the development of delayed ischemic neurological deficit (DIND) was studied retrospectively in 18 patients with ruptured aneurysm of the middle cerebral artery (MCA). Neck clipping of the aneurysms was performed via the pterional approach within 72 hours after onset of subarachnoid hemorrhage. All patients were in grade I or II of the Hunt and Hess Grading, and in group 2 or 3 on Fisher's CT classification. The age ranged from 32 to 71 with 48.1% being the mean age. The aneurysm was located on the left side in 5 patients, and on the right side in 13 patients. Arterial and venous phase were evaluated on the pre-and post operative angiograms in these patients. Arterial narrowing was divided into localized and diffuse types according to the degree, and its distribution in the arterial tree. In the venogram, opacification of the superficial sylvian veins (SSV) was the main thing evaluated. Arterial narrowing was observed in 16 cases (9; localized, 7; diffuse). In some cases, visualization of the SSV was poor or fair, and in others it was normal. DIND, including motor deficit or disturbance of consciousness, developed in 10 cases (transient; 6, permanent; 4). The patients with normal visualization of SSV on the postoperative angiogram had good outcome, even if they had diffuse arterial narrowing. On the other hand, the outcome was only fair or poor in those patients who had poor visualization of the SSV, irrespective of arterial narrowing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598134 TI - [A new principle and device for radiosurgery using a linear accelerator; its principle, devices and clinical trials]. AB - The authors have developed new devices for stereotactic radiosurgery using a conventional linear accelerator (LINAC). The system of devices consists of a rotatory chair with a base ring holder, a Brown Robert Well's stereotactic apparatus (BRW's apparatus) with a double set of base rings and a number of precise collimators which eliminate penumbra to the greatest extent. A study rotatory chair was manufactured, whose vertical axis of rotation is always set and stable. A strongly built, adjustable holder for the BRW's base ring is attached to the chair. The principle and flow of procedures step by step is as follows; 1). The rotatory chair is carried in under the linear accelerator and the vertical rotatory axis of the chair is precisely adjusted to align with the vertical center of the photon beam from the LINAC. 2) A base ring and a locator of BRW's apparatus are mounted on a patient's head and three coordinates of a target are determined by CT scans. 3) The target indicator of the dummy set of BRW's apparatus is positioned according to X, Y, Z coordinates of the target. The tip of a rod indicator fixed on an instrument bloc on the arc device is precisely adjusted to touch at the tip of the target indicator. 4) The base ring and arc device with rod indicator are transferred together from the BRW's dummy set to the rotatory chair and fixed to the base ring holder. The tip of the rod indicator is precisely adjusted to be positioned at the isocenter of the LINAC. 5) The base ring and arc device are removed and replaced by another base ring mounted on the head of a patient, who is made to sit on the rotatory chair. The target in the brain is now located at the isocenter of the LINAC. Stereotactic radiation is started with rotation of the chair and circular movement of the gantry of the LINAC. The chair is rotated at a speed of 100 degrees per second, and the gantry of the LINAC is moved slowly on a circular trajectory from +115 degrees to -115 degrees. Fourteen cases, including AVM, cavernous angioma, acoustic tumor and glioma have been treated so far. Three cases of large AVM were treated by a combination of artificial embolization and stereotactic radiosurgery.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1598135 TI - [Outcome of patients with primary malignant lymphoma of the brain; relationship to the nucleolar organizer region]. AB - Twelve cases of primary malignant lymphoma of the central nervous system had been treated since April, 1979 to August, 1990. Radiation therapy was completed in ten of them without adjuvant chemotherapy, and the other two patients expired before or during radiation therapy. In spite of good response to the radiation therapy, five of the ten patients died within 2 years. Three cases are alive after more than 5 years, and there has been no recurrence. In eight cases, the number of the argyrophilic proteins of the nucleolar organizer regions (AgNORs) was counted in the formalin-fixed paraffin embedded sections. In those cases with an AgNOR number of 4.0 or higher, prognosis was significantly worse than in the others. AgNOR number may be used as one of the reliable factors in the prognosis of primary malignant lymphoma of the central nervous system. PMID- 1598136 TI - [Intramedullary neurofibroma in the cervical spinal cord; a case report]. AB - A 62-year-old woman was admitted complaining of clumsiness in both hands. On neurological examination, bilateral hand muscles were weak, both legs were spastic and hyperreflexic, all the extremities were hypoesthetic. Urological examination revealed detruser sphincter dyssynergia. Spinal CT scan demonstrated an iso density mass lesion in the cervical spinal cord, and it was markedly enhanced. On MRI, it was also markedly enhanced by Gd-DTPA. The operative finding was that an oval shaped tumor was buried in the spinal cord and was totally removed. Its histological diagnosis was neurofibroma. Intramedullary neurofibroma is rare and only 18 cases have been reported. In this case the tumor seemed to have arisen at the root entry zone and to have grown sub-pially. PMID- 1598137 TI - [Carotid stenosis complicated by coronary disease; a case report]. AB - A 66-year-old-man with carotid stenosis complicated by coronary disease is reported. He suffered from mild motor weakness on the right side and speech disturbance. Radiological examination revealed 90% stenosis at the cervical portion of the left internal carotid artery, and two-vessel coronary disease. In order to prevent intraoperative cardiac stroke, initial percutaneous coronary angioplasty (PTCA), was performed and the subsequent carotid endarterectomy (CEA) was performed successfully. Preoperative symptoms gradually improved and he was discharged as ambulatory. Because atherosclerosis is always systemic, patients with carotid artery disease should be examined for coronary disease. We recommend greater use of coronary angiography and, when a lesion is found, the use of PTCA, which is a safer method in terms of preventing intraoperative cardiac stroke of CEA than any other method. PMID- 1598138 TI - [A case of fibromuscular dysplasia associated with intra- and extracranial multiple aneurysms]. AB - A case of fibromuscular dysplasia (FMD) with intra- and extracranial multiple aneurysms is reported. A 42-year-old woman was admitted to Kagawa Central Hospital with severe headache and stiffness of the neck. CT scan showed subarachnoid hemorrhage predominantly in the left side of the basal cisterns and hydrocephalus. Angiography at admission revealed marked stenosis and dilatation of the extracranial major arteries and multiple aneurysms in the lt. PCA, lt. ICA, bil. VA, and the lt. renal artery. String-of-beads appearance was also seen in the branches of the lt. external carotid artery. During the operation, the PCA aneurysm which has been diagnosed as the ruptured one, was found to arise from the posterior communicating artery itself. It was thus a so-called true posterior communicating aneurysm. The aneurysm was trapped by clipping the artery on both the ICA and the PCA sides. The giant aneurysm of the lt. ICA was successfully treated by lt. STA-MCA anastomosis and ligation of the lt. ICA. Postoperative angiography demonstrated no visualization of the aneurysm and total occlusion at the origin of the lt. VA that had been patent preoperatively. On histological examination, intimal and medial hyperplasia was seen in the aneurysmal wall and occipital artery biopsied at operation. There has been no report of FMD associated with multiple and very rare posterior communicating aneurysms. Wide involvement of vascular change and advance of arterial occlusion noted by serial angiography indicates that FMD is a disease in which pathology would be progressive in some cases. PMID- 1598140 TI - Occupational medicine in New Zealand. PMID- 1598139 TI - Screening for noninsulin dependent diabetes mellitus and impaired glucose tolerance in a Dunedin general practice--is it worth it? AB - AIMS: the main aims of this study were to investigate the feasibility of screening for noninsulin dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in general practice and to compare random blood glucose measurements with the two hour oral glucose tolerance test as screening methods. METHODS: one thousand, one hundred and eighty-four people aged 39-79 years who were registered with two general practitioners were invited to be screened using a random blood glucose test. Subjects who had a random test and were aged 39-69 years were subsequently invited to have a two hour oral glucose tolerance test (OGTT). Those subjects who had a raised random blood glucose level or a raised fasting and/or two hour plasma glucose level according to WHO criteria, were invited back for two additional OGTTs. RESULTS: the overall response rate for the random blood glucose testing was 67%. Forty-seven percent of those aged 50-69 years and 35% of those aged 39-49 years completed one OGTT. A number of people with high random blood glucose levels had normal OGTTs which suggests that the risk of a false positive result from the random test is high. In addition, a number of false negative results from the random test were identified. A total of 20 people were found to have IGT, although only three of these were identified from the random test which confirms the necessity of administering an OGTT for the identification of IGT. Only 44% of those identified with IGT from a single test remained in the IGT category after repeat testing. The prevalence of NIDDM and IGT for people aged 39-69 years was 4.4%. CONCLUSIONS: the random glucose test did identify people with NIDDM however this test was found to be an insensitive technique for identifying IGT. A number of cases of NIDDM and IGT did not persist after repeat testing. The small number of new diabetics diagnosed from this screening study suggests that screening for diabetes in a predominantly European general practice is not cost effective in terms of the resources required. PMID- 1598141 TI - Medications and their monitoring in Parkinson's disease in Dunedin. AB - AIMS: to establish the patterns of drug administration and monitoring in people with Parkinson's disease. METHOD: a total community sample was obtained. One hundred and one of the 116 people with Parkinson's disease in Dunedin, who were alive on 31 July 1990, had a full medical assessment. RESULTS: the general practitioner made the diagnosis in 51%, a neurologist in 22%, a geriatrician in 18%, and other in 9%. The general practitioner provided prescriptions for 51 of the 68 people living in the community, a neurologist for 11, and a geriatrician in six cases. The general practitioner provided prescriptions for 23 of the 33 living in an institution, and a geriatrician in ten cases. Medical review took place more frequently than three monthly in 49 cases. There were 81 general practitioners in practice on the prevalence day in the study area. Thirty-six had no patients with Parkinson's disease, 30 had one or two, and the other 15 had varying numbers. Fifty-eight of the 90 patients taking levodopa were taking it as the only therapy. Eight patients were taking phenothiazines. There was a high incidence of side effects and 70 patients had long term complications including loss of effectiveness over time, the end of dose and the on-off phenomena, and dyskinesias. CONCLUSIONS: monitoring of treatment appeared satisfactory but major concerns about drug management included the high use of levodopa monotherapy and the concurrent use by general practitioners of phenothiazines in eight cases. Because most general practitioners have very few patients with Parkinson's disease they will not develop the experience to manage complicated drug regimens in people whose management tends to become more difficult with time. With selegiline and controlled release levodopa only being available on specialist prescription, we suggest that all people with Parkinson's disease should have the benefit of a specialist review at least every two years. PMID- 1598142 TI - Fibreoptic bronchoscopy and bronchoalveolar lavage in the investigation of the immunocompromised lung. AB - The records of 18 immunocompromised patients with recent onset of pulmonary disease who had fibreoptic bronchoscopy and bronchoalveolar lavage over a two year period (1989-90) were reviewed. The underlying diseases were human immunodeficiency virus (HIV) infection (n = 7), organ transplantation (n = 9), and chemotherapy for malignancy (n = 2). Four patients were receiving prophylactic therapy and 12 had been started on empirical therapy for infection. Patients proceeded to bronchoscopy either because of atypical disease presentation or failure to respond to empirical therapy. Bronchoscopy with bronchoalveolar lavage was diagnostic in 13/18 (72%) patients and provided clinically useful information in 16/18 (89%). There was one diagnostic failure (6%); Pneumocystis carinii pneumonia in an HIV positive patient receiving nebulised pentamidine prophylaxis was missed. Transbronchial biopsies were not routinely performed and provided additional diagnostic information in only 1/6 (17%) patients. Overall, the commonest diagnoses were Pneumocystis carinii pneumonia (61%) and cytomegalovirus pneumonitis (28%). There were no complications of the procedures. In this highly selected setting of diagnostic or therapeutic uncertainty, fibreoptic bronchoscopy with bronchoalveolar lavage remains an effective and safe technique for evaluating pulmonary disease in immunocompromised patients. PMID- 1598143 TI - Attitudes and concerns amongst laboratory staff regarding handling of HIV positive biological specimens. AB - AIMS: to ascertain attitudes and concerns of laboratory staff towards handling of HIV positive biological samples. METHOD: an anonymous questionnaire regarding various aspects of biological sample handling was distributed to laboratory staff from the Wellington Area Health Board laboratories. RESULTS: of a total of 133 laboratory staff (response rate: 56.4%), five were seriously considering leaving, and another ten would have chosen another career if given prior information in regard to handling HIV positive biological samples. Of the responders, 22.8% and 38.3% considered that their employer does not provide adequate safety measures and education respectively in regard to HIV. CONCLUSIONS: handling of HIV positive biological samples does not greatly contribute to attrition amongst laboratory staff. Given the concern of laboratory staff for safety and education in regard to HIV, a continuous in-service educational programme would be desirable. PMID- 1598144 TI - Haemophilus influenzae in New Zealand: subtyping of isolates from invasive disease using outer membrane protein profiling. AB - Invasive Haemophilus influenzae type b disease affects one in every 350 New Zealand children by the age of five, leaving some with severe handicap. As part of a national surveillance programme aimed at determining the epidemiology of H influenzae b disease in this country, the diversity of local isolates causing invasive disease was examined using outer membrane protein (OMP) profiling. Of 81 H influenzae b isolates examined, 70 (86%) had identical OMP profiles. Among the other 11 H influenzae b isolates, eight different OMP profiles were observed. Nontype b Haemophilus influenzae isolates (n = 13) showed a greater diversity of OMP patterns. PMID- 1598145 TI - Improving a low immunisation rate in general practice. PMID- 1598146 TI - Weaning; a position statement. AB - 1. Weaning is the process by which the milk fed infant is gradually accustomed to a varied diet. 2. The time at which weaning should commence should be signalled by the infant's being dissatisfied with a milk diet. While this tends to occur around five to six months of age, it may be later. 3. Appropriate foods to start weaning should be almost liquid in consistency, provide useful nutrients, and be of low allergenicity. 4. The aim is to achieve a diet based on family foods. These should conform to the criteria for a healthful diet, but should not be especially low in fat or rich in fibre. 5. In the earlier stages breast milk or formula remains the principal source of nutrition. Weaning foods should not be used in a way which discourages consumption of milks. 6. Water or diluted fruit juice may be used to assuage thirst, but should not supplant milk even in the later stages of weaning, since they contain no calcium or most other essential micronutrients. Tea and coffee are not suitable drinks for young children. PMID- 1598147 TI - Urinary tract infections in adults: Part 1--Curative regimens of treatment. PMID- 1598149 TI - Planning health services for the elderly. PMID- 1598148 TI - Dental Council affairs. PMID- 1598150 TI - Refrigerated vaccines to be stored within boxes. PMID- 1598151 TI - Salt and blood pressure. PMID- 1598152 TI - Worldwide variation in emergency and cardiac arrest call telephone codes. PMID- 1598153 TI - HIV/AIDS and sex workers. PMID- 1598154 TI - Midwives and the maternity benefit. PMID- 1598155 TI - Midwives and the maternity benefit. PMID- 1598156 TI - The risk of occupational HIV infection. PMID- 1598157 TI - AIDS. PMID- 1598158 TI - Entrepreneuring in PA. Who is the nurse entrepreneur/intrapreneur? PMID- 1598159 TI - Entrepreneuring in PA. Visiting nurses fill niche in local industry. PMID- 1598160 TI - ANA Institute makes great strides for collective bargaining. PMID- 1598161 TI - Health care reform: how will it effect nursing? Practice perspective. PMID- 1598162 TI - Health care reform: how will it effect nursing? Implications for independent practice. PMID- 1598163 TI - Health care reform: how will it effect nursing? Nursing education. PMID- 1598164 TI - Consumer advisory on AIDS provided to public. PMID- 1598165 TI - National Immunization Campaign a success. PMID- 1598166 TI - A learning needs profile of an oncology nurse: the novice. PMID- 1598167 TI - Menus improve professional practice. PMID- 1598168 TI - The administrative role of nurse educators of baccalaureate nursing programs: an analysis of administrative skill attainment. PMID- 1598169 TI - Current advances in magnetic resonance imaging (MRI) in spinal cord trauma: review article. AB - Magnetic resonance (MR) images of 87 patients who had sustained spinal cord injuries during the past 2 years, were analyzed and compared with the corresponding clinical, surgical, and in some cases pathological findings. In addition to the standard MR imaging techniques applied in the spinal cord injuries, we also introduced some recent MRI technical achievements which are anticipated to improve diagnostic accuracy and broaden clinical application of this modality with regard to the spinal cord trauma. The recent technical advancements that we used include image enhancement, fat tissue signal suppression, three-dimensional (3-D) imaging, and magnetic resonance angiography (MRA). The reviewed post traumatic changes disclosed in these MR images were classified in 4 categories: acute, subacute, chronic, and the injury's sequelae. The essential properties of the 4 new imaging advancements are considered in relationship to the gain in diagnostic improvement of MRI of the 4 phases of patients with spinal cord trauma. PMID- 1598170 TI - Psychological and sociological theories concerning adjustment to traumatic spinal cord injury: the implications for rehabilitation. AB - During the past decades many healthcare professionals have turned their attention to describing the process of adjustment to traumatic spinal cord injury. Extensive review of the literature concerning adjustment is examined, together with an analysis of the effect which these theories have upon the healthcare provider who interacts with the client. Traditional rehabilitation has had the objective of teaching physical skills to such patients in order to achieve the highest possible level of independence. This paper challenges the rehabilitation team to broaden this concept of successful outcome. 'Living' requires more than physical survival. PMID- 1598171 TI - Use of penile prostheses to maintain external condom catheter drainage in spinal cord injury patients. AB - This is a retrospective analysis of 79 spinal cord injury patients who have had penile implants from one to 14 years. The primary indication for implants was the loss of condom catheter with a small retractile penis. Mean period after injury to when the implants were placed was 8.24 years (range 1-21 years). Mean total length of time the implants have been followed was 7.08 years (1-14 years). Sixty patients responded to our detailed questionnaire and they have been subjected to further analysis: prior to the implant 46 patients (77%) frequently lost their condoms. Fourteen of the patients (23%) had indwelling catheters, and 3 (5%) had a suprapubic cystostomy since they could not retain an external condom for urinary drainage because of retraction of a small penis. Post implant, 81% of patients had no accidents involving condom loss, while 19% still lost condoms. All indwelling catheters could be removed except for one patient who continued with a suprapubic catheter following transurethral sphincterotomy (TURS) and a penile implant. Sixty-eight percent used the implant for sex and felt their wives were satisfied. Patient satisfaction survey showed a markedly increased self esteem, increased mobility without fear of condom loss, and an improved sex life. Overall, the long term prosthesis failure rate was 8%. The specific infection complication rate was less than 2%. The Flexirod semirigid, hinged prosthesis proved ideal in meeting the requirements for these patients. PMID- 1598172 TI - Studies of bladder sensitivity in patients with myelodysplasia. AB - In 41 patients with myelodysplasia, the sensitivity in the lower urinary tract was investigated both with the evaluation of the perception of bladder filling and with the determination of the electrical sensory threshold of the urinary bladder wall. Visceral proprioceptive and/or exteroceptive bladder sensitivity proved, rather unexpectedly, to be present in a majority of the patients. The findings of these investigations did not correlate with any of the data of a clinical neurological examination. The evaluation of the sensory innervation of the lower urinary tract is of importance for diagnosis and therapy. Its investigation necessitates specific tests. PMID- 1598173 TI - Endoscopically guided bladder neck suspension for continence in paraplegic women with implant driven micturition. AB - Two paraplegic women who had undergone implantation of a sacral anterior nerve root stimulator to treat their voiding difficulties and recurrent urinary tract infections subsequently suffered from stress incontinence. After urodynamic evaluation they were treated with a Stamey operation which rendered them dry without hindering their implant driven micturition. PMID- 1598174 TI - Hyperpyrexia in spinal injury patients. AB - We studied 13 spinal injury patients who had hyperpyrexia during an 18 month period (September 1984-March 1986) to discover if differences existed in the core temperature of patients with tetraplegia and those with paraplegia, and the contribution of these differences to the final outcome. Children were excluded from this study as well as patients with any sign of infection on first admission, patients with multiple injuries, and those referred from peripheral hospitals more than one week after injury. Patients with tetraplegia (C3-C7) had persistently high and uncontrollable core temperatures (average 39.5 degrees C) while those with paraplegia (T4-L5) showed lower core temperatures which were still high (average 38.1 degrees C). The difference in the average high core temperature (1.4 degrees C) is statistically significant. The lowest average core temperatures were about the same in tetraplegics and paraplegics (just over 35 degrees C). Four patients died: 3 tetraplegics and one paraplegic. Antipyretic analgesics were ineffective in reducing the high core temperatures. PMID- 1598175 TI - Bone mineral and hormone status in paraplegics. AB - Nineteen men who had suffered permanent paraplegia a median of 4 years previously were studied. Eight also had varying degrees of neurological deficit of the upper extremities. Bone mineral, biochemical and hormonal values were compared to those in an age-matched control group in order to detect evidence of systemic osteopenia. There were very considerable individual variations in bone mineral density (BMD) deficits among patients compared to controls, probably partly due to methodological problems. Significant BMD deficits were found in the metaphysis (45%) and diaphysis (26%) of the tibia, while the deficit of the distal forearm was barely significant for the group as a whole. There was a negative correlation between time since injury and degree of BMD deficit in the lower extremity. Those with neurological affection of the upper extremities had a greater BMD deficit of their arms than those with neurologically intact arms. It was concluded that osteopenia in paraplegics is largely confined to the paralysed extremities, and thus not systemic. Serum alanine aminotransferase, phosphate, follicle stimulating hormone, and free androgen index (testosterone/sex hormone binding globulin) were mainly within normal limits, but significantly higher in paraplegics than in controls. Osteopenia in these patients is thus not due to gonadal dysfunction. PMID- 1598176 TI - Cardiovascular and vasoactive hormone responses to bladder distension in spinal and normal man. AB - Many patients with high spinal cord injury experience exaggerated blood pressure rises in response to bladder distension. To examine the humoral mechanisms associated with these responses, ECG heart rate, blood pressure and vasoactive hormone levels were measured at baseline and during bladder distension following slow bladder filling in 23 subjects: 9 high spinal lesion patients, 7 low spinal lesion patients and 7 normal control subjects. Systolic blood pressure rose significantly during bladder distension in the high spinal lesion group by an average of 56 mm Hg (48%) and diastolic blood pressure rose by 22 mm Hg (47%), while heart rate fell by a mean of 7.4 beats per minute (15%). By contrast, neither systolic or diastolic blood pressure nor heart rate changed significantly during bladder distension in the low spinal lesion or normal control group. There were no significant changes in plasma levels of noradrenaline, renin, aldosterone, vasopressin, arginine, or atrial natriuretic peptide during bladder distension to account for the blood pressure rise in the high spinal lesion group. These findings suggest that humoral mechanisms are unlikely to play a major role in the mediation of pressor responses to bladder distension in high spinal lesion patients. PMID- 1598177 TI - Fatal cerebral hemorrhage due to autonomic dysreflexia in a tetraplegic patient: case report and review. AB - Autonomic dysreflexia is the most important specific complication of high level spinal cord injury both in tetraplegic and in paraplegic patients above the midthoracic neural segment. It is a life threatening emergency that may lead to apoplexy. We present a case of fatal cerebral hemorrhage due to autonomic dysreflexia in order to demonstrate the gravity of this particular syndrome. PMID- 1598178 TI - Is the appearance of periarticular new bone formation related to local neurological disability? AB - The present work examined the relationship between the appearance of periarticular new bone formation (PNBF) and the presence of local sensorimotor disability, and the relationship between PNBF and the severity of the motor disability. The study population consisted of 18 patients with spinal cord lesions and 18 patients with traumatic brain injury. The confinement of PNBF below the level of neurological deficit in patients with spinal cord lesions, and mainly to paralysed or paretic limbs in brain injured patients, indicates a possible causal relationship between the presence of sensorimotor disability and PNBF. On the other hand, the high incidence of bilateral PNBF in patients with incomplete spinal lesions and the appearance of PNBF in some nonplegic and even paretic limbs in the brain injured patients, demonstrates the lack of connection between the severity of the motor deficit and the risk of PNBF. It is suggested that local factors which are related to sensorimotor disability are probably involved in PNBF induction, but additional elements may also play a role in the induction of PNBF and in its propagation. PMID- 1598179 TI - Long term follow up of patients with cauda equina syndrome due to intraspinal lipoma. AB - We have had the opportunity to treat and follow up two young males with cauda equina syndromes after recurrent resection of intraspinal lipomas. This condition is relatively rare. The patients underwent myelographies, operations, long periods of hospitalisation, and rehabilitation. The syndromes included low back pain, arachnoiditis, and recurrence of the lipoma after several years and multiple operations. These are the problems that we were faced with: (1) Although the tumor is benign it is impossible to resect it completely. (2) There are complications which interfere with rehabilitation, including pain, arachnoiditis, and neurological deterioration. (3) Long term prognosis might be grave and the patient and family should know this. (4) Physiotherapy and sports: should these patients perform strenuous exercise or not? PMID- 1598180 TI - Surgical considerations in patients with lumbar spinal root anomalies. AB - Lumbosacral nerve root anomalies are rare and can cause diagnostic confusion. In this report we present 12 patients with lumbar root anomalies. Emphasis is placed on preoperative neuroradiological evaluation and the surgical implications of these anomalies. PMID- 1598181 TI - Thigh compartment syndrome secondary to intertrochanteric hip fracture in a quadriplegic patient: case report. AB - Compartment syndromes in the thigh are rare and the diagnosis may be difficult in the light of subtle early physical findings in the patient with spinal cord injury. Clinical awareness of the impending compartment syndrome is important to provide timely proper treatment and avoid disabling deformities. A compartment syndrome should not be ignored in the paraplegic, because the potential for late fibrosis and contractures may limit the independence of such patients. Greater awareness and index of suspicion are needed to successfully recognize and promptly treat the compartment syndrome in this patient population. PMID- 1598182 TI - Fever response of sheep in the peripartum period to gram-negative and gram positive pyrogens. AB - We have measured body temperatures and serum iron concentrations of sheep in the peripartum period following administration of endotoxin and Staphylococcus aureus cell walls. Both the rise in rectal temperature and the fall in serum iron concentration following intravenous injection of S. aureus were the same immediately pre- and postpartum as they were 5 weeks after parturition. The rise in rectal temperature following intravenous endotoxin injection immediately pre- and postpartum was significantly less than that of the same ewes 5 weeks later. However, the fall in serum iron concentration following endotoxin injection was significantly suppressed only prepartum. We conclude that fever is not suppressed in sheep in the peripartum period, but the response to endotoxin is suppressed, through complex processes incidental to the mechanism responsible for the maintenance of gestation and induction of labour. PMID- 1598183 TI - Monitoring the surface tension of lipid membranes by a bubble method. AB - A new method for the determination of lipid membrane surface tension was developed. Advantages of this method are that it allows for multiple measurements on a single membrane, is fast and direct not requiring empirical corrections, may be applied for dynamical surface-tension measurements and may be used with thin films and asymmetrical electrolytes. The pressure and radius of a bubble are measured. A piezoresistive sensor is used to minimize the transducer compliance. By moulding the sensor to a brass plate a resolution of 0.025 mm H2O (0.25 Pa) is obtained. The bubble is filmed using a videocamera and the radius of the bubble determined with the aid of a microcomputer. Data for monoolein/hexadecane in potassium chloride solutions and a cooling curve are presented and compared with previous results. PMID- 1598184 TI - Active NaCl transport in the cortical thick ascending limb of Henle's loop of the mouse does not require the presence of bicarbonate. AB - The aim of the present study was to investigate whether bicarbonate buffer (CO2 + HCO3-) is required to sustain maximal NaCl transport in the cortical thick ascending limb of Henle's loop (cTAL) of the mouse. Transepithelial Na+ and Cl- net fluxes (JNa, JCl, pmol min-1 mm-1), measured by electron microprobe analysis, were similar irrespective of the presence or absence of CO2 + HCO3- in luminal and bathing solutions (JNaCl with CO2 + HCO3- = 203 +/- 25 pmol min-1 mm-1; JNaCl without CO2 + HCO3- = 213 +/- 13 pmol min-1 mm-1, n = 14). Furthermore the transepithelial potential difference, Vte, the transepithelial resistance, Rte, and the basolateral membrane potential, Vbl, were unaffected by CO2 + HCO3-. In the absence of CO2 + HCO3-, Vte was +17.0 +/- 1.7 mV (n = 9) (lumen positive), Rte was 28 +/- 2 omega cm2 (n = 9) and Vbl was -76 +/- 4 mV (n = 6). In the presence of CO2 + HCO3-, Vte, Rte and Vbl were +15.9 +/- 1.5 mV, 29 +/- 1 omega cm2 and -73 +/- 5 mV, respectively. 4-Acetamido-4'-isothiocyanatostilbene-2,2' disulphonic acid (SITS; 0.1 mmol l-1) and amiloride (1 mmol l-1) added to the (CO2 + HCO3-)-containing lumen perfusate were without effect on Vte and Rte. Finally, the effect of furosemide (0.1 mmol l-1) on Vte and Vbl in the presence of CO2 + HCO3- was investigated. Furosemide reversibly decreased Vte from +13.7 +/- 1.1 mV to +1.7 +/- 0.7 mV (n = 6) and hyperpolarized Vbl from -70 +/- 1 to 89 +/- 3 mV (n = 5), suggesting passive distribution of Cl- across the basolateral membrane. In conclusion, these data suggest that active NaCl transport in the cTAL of the mouse does not require the presence of CO2 + HCO3-. PMID- 1598185 TI - Effects of ammonium chloride on membrane currents of acinar cells dispersed from the rat parotid gland. AB - In acinar cells freshly dispersed from rat parotid glands, the effects of ammonium chloride (NH4Cl) on membrane currents were studied using the whole-cell clamp method. When membrane currents were recorded with command pulses to 0 mV, applied at 2-s intervals from a holding potential of -70 mV, NH4Cl (5-20 mM) transiently decreased outward currents and then slowly increased both outward and inward currents. After reaching a peak in about 40-50 s, both outward and inward currents gradually decreased in the presence of NH4Cl and, on its wash-out, the currents returned to the control level. Butyrate (5-20 mM) had little effect on the resting membrane currents, but markedly inhibited the response to NH4Cl. Tetraethylammonium (5 mM) strongly reduced both the resting and NH4Cl-induced outward currents, whereas it slightly potentiated the NH4Cl-induced inward current without affecting the membrane current at the holding potential. Without ATP in the patch pipettes, carbachol-induced membrane currents were relatively resistant to Ca2+ removal from the external medium, but NH4Cl-induced currents were quickly abolished in the absence of Ca2+. We conclude that intracellular alkalinization with NH4Cl increases Ca2+ influx and activates Ca(2+)-dependent outward K+ and inward Cl- currents. PMID- 1598187 TI - Inositol trisphosphate may access calcium from stores not coupled to muscarinic receptors in Xenopus oocytes. AB - Oocytes of a large fraction of Xenopus females exhibit a complex response to acetylcholine (ACh) consisting of rapid, transient and prolonged, slow chloride currents. Frequent consecutive challenges or a single prolonged challenge with ACh result in a marked decrease in response amplitudes, i.e. refractoriness. In ACh-refractory oocytes, the response to injected inositol 1,4,5-trisphosphate (InsP3), the intracellular mediator of the ACh response, is not affected. Similarly, InsP3-evoked responses were obtained in oocytes that lacked muscarinic response or that lost their responsiveness as a result of progesterone-induced maturation. To investigate the mechanism of this phenomenon, we have depleted intracellular calcium stores by repeated challenges with ACh in calcium-free medium. Disappearance of the ACh response through depletion of the ACh-coupled calcium store did not prevent a subsequent response to InsP3. These results imply that InsP3 can mobilize calcium from other stores, not depleted by previous exposure to ACh. This finding is further reinforced by our results that demonstrate that ACh causes 45Ca efflux in responsive oocytes, while InsP3 in supramaximal concentrations does not induce 45Ca efflux. Indeed, InsP3 can induce 45Ca efflux only when more than 2 pmol/oocyte is injected. This is also the concentration of InsP3 that desensitizes the InsP3 response. These data suggest that InsP3 also releases cellular calcium from stores different from those mobilized by ACh. PMID- 1598186 TI - Patch-clamp analysis of voltage-gated currents in intermediate lobe cells from rat pituitary thin slices. AB - Ionic currents of hypophyseal intermediate lobe cells were studied using a thin slice preparation of the rat pituitary in conjunction with conventional and perforated whole-cell patch-clamp recording techniques. A majority (89%) of the cells studied generated Na+, Ca2+ and K+ currents upon depolarizing voltage steps and responded to bath application of gamma-aminobutyric acid (GABA; 20-50 microM) with inward currents (in symmetrical chloride, holding potential -80 mV). A small percentage of cells (11%) did not display inward membrane currents upon depolarization and was unresponsive to GABA. In the first type of cells, Ca2+ and K+ currents were further studied in isolation. Ca2+ tail currents showed a biphasic time course upon repolarization, with time constants and amplitudes of 2.07 +/- 0.29 ms, 123 +/- 22 pA (for the slowly deactivating component) and 0.14 +/- 0.06 ms, 437 +/- 33 pA (for the fast-deactivating component; means +/- SD of n = 4 cells). Slowly and fast-deactivating conductances were half-maximally activated at around -10 mV and +10 mV respectively. Depolarizing voltage steps elicited two types of K+ current, which were separated using a prepulse protocol. A fast-activating, transient component showed half-maximal steady-state inactivation between -65 mV and -45 mV depending on the divalent cation composition of the external solution. Its decay was fitted by single-exponential functions with time constants of 36 +/- 11 ms and 3.9 +/- 0.9 ms at -20 mV and +40 mV respectively (mean +/- SD; n = 4 cells). Whereas the peak current amplitudes of the transient K+ current component remained stable, the amplitude of the second, delayed component increased progressively throughout the course of whole-cell experiments. In cells recorded with the perforated whole-cell technique, bath application of dopamine (10 nM-1 microM) induced large hyperpolarizations from a spontaneous membrane potential of -40 mV, but did not consistently affect the amplitude of the voltage-gated K+ conductances. These data are compared to previous studies using other preparations of the intermediate lobe, and differences are discussed, thus helping to extend our knowledge of electrical excitability of hypophyseal cells. PMID- 1598188 TI - Transport of putrescine in the isolated rabbit intestine. AB - The transepithelial fluxes of putrescine were studied in sections of the three segments of rabbit intestine mounted in an Ussing chamber. The ileum exhibited the highest mucosal-to-serosal (Jms) and serosal-to-mucosal (Jsm) unidirectional fluxes of 1 mumol/l [3H]putrescine. Putrescine net flux (Jnet = Jms - Jsm) was deduced to be positive through the duodenum (Jnet = 53.40 +/- 14.30 pmol h-1 cm 2), not significantly different from zero through the jejunum (Jnet = 8.90 +/- 19.20 pmol h-1 cm-2) and negative through the ileum (Jnet = -34.30 +/- 13.80 pmol h-1 cm-2). Increasing putrescine concentration up to 10 mmol/l led to an increase in Jms, Jsm and Jnet without affecting the transport polarity in the ileum. The tissue retention of putrescine after 100 min was higher by the serosal side than by the mucosal side of the ileum. In parallel experiments, isolated pieces of ileum accumulated putrescine to a five- to sixfold concentration gradient by a ouabain-inhibitable mechanism. In contrast with arginine and in order of decreasing potency, putrescine, cystamine (a transglutaminase inhibitor), spermidine and spermine (1 mmol/l) reduced both unidirectional fluxes of putrescine across the ileum in the Ussing chamber. The latter effectors, except spermine, and N,N-dimethylcasein (1 mg/ml) led to an important, if not complete, suppression of putrescine secretion by the ileum, while the calmodulin antagonist melittin (0.3 micrograms/ml) reversed the polarity of polyamine transport, suggesting the involvement of transglutaminase in putrescine transport. We conclude that the heterogeneous pattern of putrescine transport along the small intestinal epithelium constitutes an important feature of the regulation of polyamine concentrations in this tissue. PMID- 1598189 TI - Intracellular Mg2+ inhibits the IP3-activated IK(Ca) in NG108-15 cells. [Why intracellular citrate can be useful for recording IK(Ca)]. AB - Receptor-mediated formation of inositol 1,4,5-trisphosphate (IP3) can induce an outward Ca(2+)-activated K+ current [IK(Ca)] in some neural cells. We have investigated IK(Ca) activated by intracellular injections of IP3 in whole-cell patch-clamped neuroblastoma x glioma hybrid cells. The current could only be recorded reliably using citrate as the anion in the pipette, but not using acetate, aspartate, chloride, fluoride, gluconate or methylsulphate. This could be attributed to buffering of intracellular Mg2+ by citrate. Theoretical calculations suggested free [Mg2+] of 1.0 and 0.07 mM respectively in the acetate and citrate-based recording solutions. Further, IP3-activated IK(Ca) could be recorded when the free Mg2+ level in the acetate, chloride or methylsulphate solutions was lowered to the range (0.05 mM) calculated for the citrate solution. Thus, raised [Mg2+] blocks IK(Ca). This appeared to be due to inhibition of the response to released Ca2+, since high [Mg2+] also blocked the response to intracellular injections of Ca2+ ions. Mean Mg2+ levels in intact neuroblastoma x glioma hybrid cells measured by Mag-Indo-1/AM fluorescence were estimated to be less than 0.14 mM. We therefore conclude that IP3-induced IK(Ca) is expressed under normal conditions, but may be subject to regulation by intracellular Mg2+. PMID- 1598190 TI - High energy phosphates and related compounds, glycogen levels and histology in the rat tibialis anterior muscle after forced lengthening and isometric exercise. AB - Eccentric exercise may elicit damage to the contractile elements. This primary damage is followed by secondary changes, consisting of histological changes and changes in glycogen and energy metabolism. The mechanism underlying changes in glycogen homeostasis and energy metabolism is not well established. The aim of this study was to investigate the possible relationship between changes in adenine and guanine nucleotides, inosine monophosphate (IMP), creatine phosphate, glycogen content and histology in the rat tibialis anterior (TA) muscle after forced lengthening or isometric exercise. The right muscles were either forcibly lengthened or isometrically exercised, while the contralateral muscles served as non-exercised controls. The exercised muscles were dissected 0, 6 and 24 h post exercise and the contents of adenine and guanine nucleotides, IMP, creatine phosphate, and glycogen determined. In addition, histological changes were assessed. Immediately after both types of exercise increases in tissue IMP levels were found. Irrespective of the type of exercise, glycogen content was decreased immediately post-exercise, but restored 6 h post-exercise. Twenty-four hours later a second decline in glycogen content was found after both types of exercise. In forcibly lengthened muscles ATP content was decreased 24 h post exercise. In isometrically exercised muscles ATP was not decreased at any time. Gross structural changes were found in all forcibly lengthened muscles (9-12% of TA muscle volume). In isometrically exercised muscles structural changes were minor (up to 0.1% of muscle volume), were found only immediately post-exercise and in only 4 out of 18 muscles. It is concluded that forced lengthening results in decreased ATP levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598191 TI - Metabolite patterns related to exhaustion, recovery and transformation of chronically stimulated rabbit fast-twitch muscle. AB - Rabbit fast-twitch tibialis anterior muscle was subjected to chronic low frequency stimulation (10 Hz, 24 h/day). Measurements of the time course of changes in the concentration of metabolites of energy metabolism were performed in order to test the hypothesis whether or not alterations in the metabolite profile might represent possible signals for triggering muscle fibre type transformation. Most of the investigated metabolites displayed triphasic changes in response to persistently increased contractile activity. During the first 15 min of stimulation, drastic reductions were observed for adenosine triphosphate (ATP, 56%), phosphocreatine (PCr, 60%) and glycogen (76%), as well as 3- to 4 fold and 10-fold increases for glucose and lactate, respectively. This early metabolic perturbance coincided with a rapid reduction of isometric force. The next phase, extending to 4 days of stimulation, was characterized by a nearly complete recovery of ATP and PCr, and an overshoot in glycogen. The first signs of metabolic recovery were already detectable in 60-min-stimulated muscle when isometric force was still markedly depressed. These results demonstrated an impressive capability of the muscle to recover with ongoing stimulation from an initial, dramatic disturbance in energy metabolism. During the final phase, extending to 50 days, the metabolite profile approached that of a slow-twitch muscle with moderate reductions in total adenine nucleotides, ATP, total creatine, PCr and glycogen. A conspicuous result was the finding that, contrary to the recovery of most metabolites, the ratio of ATP to the product of free adenosine diphosphate and resting free inorganic phosphate was persistently depressed with ongoing stimulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598192 TI - Renal tubular reabsorption of 1,5-anhydro-D-glucitol and D-mannose in vivo in the rat. AB - 1,5-Anhydro-D-glucitol (AG) is efficiently reabsorbed in renal tubuli by a mechanism that is saturated at high AG concentrations. To gain insight into the stereospecific requirements of the mechanism, we employed an in vivo loading test technique in which rats were injected with anhydrosugars and aldohexoses in doses that led to excretion of the sugar injected, thus saturating tubular reabsorption. Administration of AG elicited an increase in the excretion of D mannose (P less than 0.0005), while D-mannose caused AG to appear in urine. Administration of 1,5-anhydro-D-mannitol led to increased excretion of D-mannose (P less than 0.0005) and the appearance of AG in urine. The effects of 1,5 anhydro-D-mannitol on the excretion of D-mannose and AG, and the effect of D mannose on AG were dependent on the dose. Myoinositiol, mannitol and C-3-C-6 epimers of AG did not interfere with the reabsorption. The mechanism was highly phlorizin-sensitive. Repeated administration of 1,5-anhydro-D-mannitol rapidly depleted the rat organism from mobilizable AG. The AG space calculated (53% of body weight) suggested the presence of considerable cellular stores of AG. D Mannose and AG are regular components of the plasma monosaccharide profile. The data suggest that the two sugars are reabsorbed in renal tubuli by a common mechanism, which is distinct from the main D-glucose reabsorption system. The presence of a glucose-type C-3-C-6 and pyranose structure is required for a sugar to be transported by the system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598193 TI - Microinjections of vasopressin in the locus coeruleus complex affect posture and vestibulospinal reflexes in decerebrate cats. AB - Vasopressin (VP) acts as a neurotransmitter or a neuromodulator on noradrenergic locus coeruleus (LC) neurons by exciting them. Experiments were performed in precollicular decerebrate cats to investigate whether direct infusion of VP into the LC complex of one side produced changes in posture as well as in the gain of vestibulospinal reflexes acting on forelimb extensors. Unilateral microinjection of 0.25 microliters VP solution (10(-11) micrograms/microliters saline) into the LC complex increased the extensor rigidity in the ipsilateral limbs, while that of the contralateral limbs either remained unmodified or slightly decreased. The amplitude of modulation and thus the response gain of both the ipsilateral and the contralateral triceps brachii to roll tilt of the animal leading to stimulation of labyrinth receptors decreased (t-test, P less than 0.001 for both the ipsilateral and the contralateral responses). Moreover, a slight decrease in phase lead of the responses was observed. These findings occurred 5-10 min after the injection, were fully developed within 30 min and disappeared in about 2 h. The changes in posture as well as in the gain of vestibulospinal reflexes described above were site specific and depended upon the injected neuropeptide. They were attributed to tonic activation of presumptive noradrenergic neurons, which exert a facilitatory influence on limb extensor motoneurons either directly, by utilizing the coeruleospinal pathway, or indirectly by inhibiting the dorsal pontine reticular formation and the related medullary inhibitory reticulospinal neurons. PMID- 1598194 TI - K+ channels in PC12 cells are affected by propofol. AB - The effect on K+ currents (IK) of the general anaesthetic propofol (PR) (2,6 diisopropylphenol) was tested in undifferentiated clonal pheochromocytoma (PC 12) cells using the patch-clamp technique in whole-cell and single-channel configurations. PR decreased macroscopic IK amplitudes in a concentration dependent way from 50 microM to 1 mM. The blocking effect was unchanged by repetitive depolarizing pulses and it was independent of the holding potential. Whereas activation of IK in control conditions was fitted by sigmoidal plus exponential time courses, only the sigmoidal time course gave an adequate fit with PR in the bath. The above effects were reversible. PR concentrations below 140 microM decreased single-channel activity for K+ channels with unitary conductance of 22 pS, in the voltage range between -40 and 60 mV from a holding potential of -50 mV. In contrast, the anaesthetic had nearly no effect on the opening probability of a channel with conductance of 10 pS. The unitary current amplitudes were unaffected in both channel types. These results suggest that PR action on IK may depend on the different blocking mechanisms of the K+ channels. PMID- 1598195 TI - Whole cell recordings from respiratory neurons in the medulla of brainstem-spinal cord preparations isolated from newborn rats. AB - In brainstem-spinal cord preparations isolated from newborn rats, a whole cell recording technique was applied to record membrane potentials of inspiratory (Insp) and pre-inspiratory (Pre-I) neurons in the ventrolateral medulla. Labelling of these respiratory neurons with Lucifer Yellow allowed analysis of their locations and morphology. Intracellular membrane potentials from 25 Insp neurons were recorded. Average resting membrane potential was -49 mV (n = 25) and input resistance was 306 M omega. Insp neurons were classified into three types from the patterns of synaptic potentials. Type I neurons (n = 11) had a high probability of excitatory postsynaptic potentials (EPSPs) in the pre- and post inspiratory phases. Type II neurons (n = 7) showed abrupt transition to the burst phase from the resting potential level without increased EPSPs in the preinspiratory phase. Type III neurons (n = 7) were hyperpolarized by inhibitory postsynaptic potentials (IPSPs) in the pre- and post-inspiratory phases. These Insp neurons, located in the ventrolateral medulla 80-490 microns from the ventral surface, were 10-30 microns in diameter, and had various soma shapes (pyramidal, spherical or fusiform). Intracellular membrane potentials from 24 Pre I neurons were recorded. The average resting membrane potential was -45 mV (n = 24), and the input resistance was 320 M omega. Typical Pre-I neurons showed fairly great depolarization accompanied by action potentials during their burst phase and repolarization during the inspiratory phase. Most Pre-I neurons appeared to have a high level of synaptic activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598196 TI - Effects of aging on the mechanical threshold of rat skeletal muscle fibers. AB - Mechanical threshold was measured "in vitro" in extensor digitorum longus (EDL) muscle fibers from rats of 3-4 and 29 months of age, by means of a two microelectrode "point" voltage clamp. The potential needed for evoking a barly visible contraction was determined using depolarizing command pulses of 5-500 ms duration. At each pulse duration, the EDL fibers from aged rats contracted at a significantly more negative potential than did those from the younger adult rats. Accordingly, the strength duration curve of the aged EDL was significantly shifted towards more negative potentials compared to that for adult rats. The rheobase voltages estimated from the fit of such curves were -62.6 +/- 0.81 mV and -57.1 +/- 0.87 mV in aged and adult EDL fibers, respectively. The data suggest that changes in excitation-contraction coupling parallel the prolongation of contractile times observed during aging in mammalian skeletal muscle. These results are consistent with the known reduction in rate and extent of Ca++ uptake by sarcoplasmic reticulum in aged rats. PMID- 1598197 TI - The dihydropyridine niguldipine inhibits T-type Ca2+ currents in atrial myocytes. AB - The whole-cell tight seal recording technique was used to investigate the effects of niguldipine, a novel dihydropyridine, on Ca2+ currents in guinea pig atrial cells. Ca2+ currents were separated into T-type and L-type components by an appropriate voltage protocol. Extracellular application of 1 microM (+/-) niguldipine (NIG) resulted in a pronounced blockade of both T-type (to 20 +/- 10% of control, n = 5) and L-type Ca2+ currents (to 28 +/- 12% of control, n = 5). Current to voltage relationships clearly showed that both Ca2+ currents were blocked over the whole voltage range examined (-60 to +40 mV). The inhibitory effect of niguldipine on T-type Ca2+ currents was found to be voltage-dependent, i.e. prolonged hyperpolarization to -90 mV led to a partial and transient removal of NIG block. The IC50 for T-type Ca2+ current inhibition by (+/-)-NIG was determined as 0.18 microM. NIG action is stereospecific. (+)-niguldipine was found to be more potent than (-)-niguldipine in blocking both Ca2+ currents. This study demonstrates the Ca2+ antagonistic action of the dihydropyridine NIG, which may not discriminate between T- and L-type Ca2+ channels. PMID- 1598198 TI - Cell cycle control of DNA synthesis in budding yeast. PMID- 1598199 TI - Proton NMR study of the [d(ACGTATACGT)]2-2echinomycin complex: conformational changes between echinomycin binding sites. AB - The interactions of echinomycin and the DNA decamer [d(ACGTATACGT)]2 were studied by proton NMR. Echinomycin binds cooperatively as a bisintercalator at the CpG steps. The terminal A.T base pairs are Hoogsteen base paired, but none of the four central A.T base pairs are Hoogsteen base paired. However, binding of the drug induces unwinding of the DNA which is propagated to the central ApT step. All four central A.T base pairs are destabilized relative to those in the free DNA. Furthermore, based on these and other results from our laboratory, we conclude that the formation of stable Hoogsteen base pairs may not be the relevant structural change in vivo. The structural changes propagated between adjacent ACGT binding sites are the unwinding of the duplex and destabilization of the base pairing between binding sites. PMID- 1598200 TI - Chemical synthesis of 2'-deoxyoligonucleotides containing 5-fluoro-2' deoxycytidine. AB - 2'-Deoxyoligonucleotides with 5-fluorocytosine residues incorporated at specific positions of the nucleotide sequence are tools of great potential in the study of the catalytic mechanism by which DNA cytosine methyltransferases methylate the 5 position of DNA cytosine residues in specific sequence contexts. Chemical synthesis of such oligonucleotides is described. Two alternative approaches have been developed, one of which proceeds via a fully protected phosphoramidite of 5 fluoro-4-methylmercapto-2'-deoxyuridine 2, the other via a fully protected phosphoramidite of 5-fluoro-2'-deoxycytidine 3. Either building block can be used in automated oligonucleotide synthesis applying standard elongation cycles and deprotection procedures exclusively. The methylmercapto function of 2 is replaced by an amino group in the final ammonia treatment used for cleavage from support and base deprotection. PMID- 1598202 TI - Field inversion gel electrophoresis in denaturing polyacrylamide gels. AB - The velocities of single stranded DNA molecules in denaturing polyacrylamide gels during symmetric and asymmetric field inversion were measured at different pulse times and gel concentrations. Under the conditions chosen in our study, pulse times as short as a few milliseconds lead to a retardation of DNA molecules larger than 400 bases. We found that a field inversion with an electric field in the forward direction of about double the strength of that applied in the backward direction is a good compromise between the degree of retardation, the temperature control requirements and the run time of the gel. PMID- 1598201 TI - Members of the rel/NF-kappa B family of transcriptional regulatory proteins bind the HRAS1 minisatellite DNA sequence. AB - The 28 base pair repeat unit of a minisatellite 1000 bp downstream from the human HRAS1 gene (VTRHRAS1) bound four proteins (p45, p50, p72 and p85) in nuclear extracts from a variety of human cell lines which were indistinguishable from several members of the rel/NF-kappa B family of transcriptional regulatory factors. VTRHRAS1 bound the constitutively expressed, but not the inducible, forms of these proteins. Analysis of partially purified binding factors from different cell lines demonstrated qualitative differences in the p50 subunit; phosphocellulose fractionation also revealed considerable heterogeneity in the p72 and p85 subunits. These results suggest the possibility that the HRAS1 minisatellite, in serving as a tandem array of rel/NF-kappa B binding sites, may function in the transcriptional regulation of HRAS1 and nearby genes. PMID- 1598203 TI - The C terminus of the NF-kappa B p50 precursor and an I kappa B isoform contain transcription activation domains. AB - The p50 subunit of the NF-kappa B transcription complex is derived from the N terminal half of a larger precursor protein, p105. Although a fair amount is known about functions located within the p50 sequences, less is known about the C terminal half of p105. In this report, we have identified a potent transcription activation domain located in the C terminus of mouse p105. In addition, the I kappa B beta proteins chicken p40 and human MAD-3, proteins that are related to the p105 C terminus, strongly activated transcription in chicken cells and yeast when fused to GAL4 DNA-binding sequences. Furthermore, chicken p40 is primarily located in the nucleus of chicken cells when overexpressed from a retroviral vector. Our results suggest novel models for the function and regulation of NF kappa B transcription complexes. PMID- 1598204 TI - Genomic organization of the halophilic archaeon Haloferax mediterranei: physical map of the chromosome. AB - Pulsed field gel electrophoresis (PFG) has been used to study the genomic organization of the halophilic archaeon Haloferax mediterranei. Analysis of the different genomic elements as well as the restriction patterns obtained with several endonucleases revealed that this microorganism has a circular chromosome of 2.9 Mb and, at least, three extrachromosomal elements of 490, 320 and 130 kb respectively. The complete physical map of the chromosome for the endonucleases PacI and BamHI has been constructed, and several BcII, BgIII and DraI restriction fragments have been aligned on these maps. The localization of heterologous and homologous genes on the physical map, including those for rRNA, lay the ground work for the construction of a genetic map. PMID- 1598205 TI - DNA sequencing with dye-labeled terminators and T7 DNA polymerase: effect of dyes and dNTPs on incorporation of dye-terminators and probability analysis of termination fragments. AB - The incorporation of fluorescently labeled dideoxynucleotides by T7 DNA polymerase is optimized by the use of Mn2+, fluorescein analogs and four 2' deoxyribonucleoside 5'-O-(1-thiotriphosphates) (dNTP alpha S's). The one-tube extension protocol was tested on single-stranded templates, as well as PCR fragments which were made single-stranded by digestion with T7 gene 6 exonuclease. Dye primer sequencing using four dNTP alpha S's was shown to give uniform termination patterns which were comparable to four dNTPs. Efficiency of the polymerase also appeared to improve with the dNTP alpha S's. A mathematical model was developed to predict the pattern of termination based on enzyme activity and ratios of ddNTP/dNTPs. This method can be used to optimize sequencing reactions and to estimate enzyme discrimination constants of chain terminators. PMID- 1598206 TI - Mapping functional regions of the segment-specific transcription factor Krox-20. AB - Krox-20, a zinc finger transcription factor with similarity to Sp1, is likely to play an important role in the development of the vertebrate central nervous system. A knowledge of its molecular properties will help to understand its physiological functions. We have therefore performed a structure-function analysis of the protein to identify the regions involved in DNA-binding and transcriptional activation. Our data suggest that only the zinc fingers are required for high affinity, specific DNA-binding. Transcriptional activation was not affected by deletion of the C-terminal tail of the protein. In contrast, deletion of the N-terminal half, upstream of the zinc fingers, completely abolished transactivation without affecting DNA-binding or nuclear localization. Two transcriptional activation domains were identified in this region. They cooperate to establish full activity. They are rich in negatively-charged amino acids and are therefore may constitute acidic activation domains. Comparative analysis of the amino acid sequences of several zinc finger proteins belonging to the Krox-20 subfamily indicates that they contain acidic regions at similar locations within their N-terminal region, suggesting that the functional organization of these proteins has been conserved during evolution. PMID- 1598207 TI - A novel blocker-PCR method for detection of rare mutant alleles in the presence of an excess amount of normal DNA. AB - A novel polymerase chain reaction method was developed to preferentially amplify a segment of DNA containing a base substitution mutation. This technique uses a pair of dideoxynucleotide-labeled oligonucleotides (18 mers) of normal sequences as blockers located between the two primers. By virtue of a subtle difference in the melting temperature between the blocker-normal DNA and blocker-mutant DNA hybrids, the method allows preferential amplification of the mutant DNA. We used the human N-ras gene as a model. Two different types of N-ras mutations could be effectively amplified when they were present with an excess amount of normal DNA at a ratio of 1:10(3). Furthermore, the sensitivity was increased 10-fold by using single strand conformation polymorphism analysis for the amplified products, and mutant DNA was detected in the presence of a 10(4) times excess amount of normal DNA. PMID- 1598209 TI - Multiple alignment using simulated annealing: branch point definition in human mRNA splicing. AB - A method for the simultaneous alignment of a very large number of sequences using simulated annealing is presented. The total running time of the algorithm does not depend explicitly on the number of sequences treated. The method has been used for the simultaneous alignment of 1462 human intron sequences upstream of the intron-exon boundary. The consensus sequence of the aligned set together with a calculation of the Shannon information clearly shows that several sequence motives are conserved: (i) a previously undetected guanosine rich region, (ii) the branch point and (iii) the polypyrimidine tract. The nucleotide frequencies at each position of the branch point consensus sequence qualitatively reproduce the frequencies of the experimentally determined branch points. PMID- 1598208 TI - A cell-free extract from yeast cells for studying mRNA turnover. AB - We have isolated a cell-free extract from yeast cells that reproduces the differences observed in vivo in the rate of turnover of individual yeast mRNAs. Detailed analysis of the degradation of yeast phosphoglycerate kinase (PGK) mRNA in this system demonstrated that both natural and synthetically prepared PGK transcripts are degraded by the same pathway previously established by us in vivo, consisting of endonucleolytic cleavage at a number of 5'-GGUG-3' sequence motifs within a short target region located close to the 3'-end of the coding sequence followed by 5'-3' exonucleolytic removal of the resulting fragments. The extract, therefore, is suitable for studying the mechanistic details of mRNA turnover in yeast. As a first application of this system we have performed a limited mutational analysis of two of the GGUG motifs within the endonucleolytic target region of the PGK transcript. The results show that sequence changes in either motif abolish cleavage at the mutated site only, indicating the involvement of the residues in question in selection of the cleavage positions. PMID- 1598210 TI - T7 promoter contacts essential for promoter activity in vivo. AB - T7 RNA polymerase promoters consist of a highly conserved 23 base-pair sequence that spans the site of the initiation of transcription (+1) and extends from -17 to +6. To determine the bases within the T7 consensus promoter that are essential for promoter function a library of mutant T7 promoters was constructed, and the in vivo activity of the mutant promoters was correlated to their sequence. The library of mutant promoters was created by randomly mutagenizing the T7 phi 10 promoter between positions -22 and +6 during the synthesis of oligonucleotides containing the phi 10 promoter. The mutagenized oligonucleotides were then ligated to a promoterless chloramphenicol acetyl transferase gene creating a plasmid (pCM-X#) that can potentially express chloramphenicol acetyl transferase in the presence of T7 RNA polymerase. E. coli containing pCM-X# and a second compatible plasmid carrying T7 gene 1 (T7 RNA polymerase) were screened for chloramphenicol resistance or chloramphenicol sensitivity. The point mutations that were found to inactivate a T7 promoter are a C to A or G substitution at -7, a T to A substitution at -8, a C to A, T, or G substitution at -9, and a G to T substitution at -11. PMID- 1598211 TI - Two upstream elements activate transcription of a major histocompatibility complex class I gene in vitro. AB - Expression of major histocompatibility complex (MHC) class I genes exhibits unique tissue and developmental specificity. In an effort to study molecular mechanisms of MHC class I gene regulation, an in vitro transcription system has been established. In B cell nuclear extracts a template DNA containing the mouse H-2Ld promoter sequence accurately directed RNA polymerase II-dependent transcription of a G-free cassette. A conserved class I regulatory complex previously shown to moderately enhance promoter activity in vivo enhanced transcription in vitro by 2-3 fold. Much of this enhancement was accounted for by a 40 bp fragment within the complex, which was capable of activating a basal H 2Ld promoter in either orientation. Farther downstream, another element called site B was identified, which independently activated MHC class I transcription in vitro by 2-4 fold. Site B bound a specific nuclear factor(s) through an NF-1 binding site but not through a neighboring CCAAT site. The functional significance of site B in vivo was demonstrated in transfection experiments in which site B enhanced MHC class I promoter activity to a degree comparable to that seen in vitro. With the identification of the two upstream activators, MHC class I genes may serve as a model to study roles of sequence-specific DNA binding proteins in transcription in vitro. PMID- 1598212 TI - DNA methyltransferase is developmentally expressed in replicating and non replicating male germ cells. AB - Genomic methylation patterns are established during maturation of primordial germ cells and during gametogenesis. While methylation is linked to DNA replication in somatic cells, active de novo methylation and demethylation occur in post replicative spermatocytes during meiotic prophase (1). We have examined differentiating male germ cells for alternative forms of DNA (cytosine-5) methyltransferase (DNA MTase) and have found a 6.2 kb DNA MTase mRNA that is present in appreciable quantities only in testis; in post-replicative pachytene spermatocytes it is the predominant form of DNA MTase mRNA. The 5.2 kb DNA MTase mRNA, characteristic of all somatic cells, was detected in isolated type A and B spermatogonia and haploid round spermatids. Immunobolt analysis detected a protein in spermatogenic cells with a relative mass of 180,000-200,000, which is close to the known size of the somatic form of mammalian DNA MTase. The demonstration of the differential developmental expression of DNA MTase in male germ cells argues for a role for testicular DNA methylation events, not only during replication in premeiotic cells, but also during meiotic prophase and postmeiotic development. PMID- 1598213 TI - DnaA dependent replication of plasmid R1 occurs in the presence of point mutations that disrupt the dnaA box of oriR. AB - We have found that DnaA dependent replication of R1 still occurred when 5 of the 9 bases in the dnaA box present in oriR were changed by site directed mutagenesis although the replication efficiency decreased to 20% and 70% of the wild-type origin in vitro and in vivo respectively. Additional mutation of a second dnaA box, 28 bp upstream oriR, that differs in only one base from the consensus sequence, did not affect the level of replication whereas polyclonal antibodies against DnaA totally abolished in vitro replication in the absence of the dnaA box. Wild-type RepA as well as a RepA mutant, RepA2623, that binds to oriR but that is inactive in promoting in vitro replication of plasmid R1, induce efficient binding of DnaA to the dnaA box. However, specific binding of DnaA to oriR was not detected by DNase I protection experiments in the absence of the dnaA box. These results suggest that the entrance of the DnaA protein in oriR is promoted initially by interactions with a RepA-oriR pre-initiation complex and that, in the absence of the dnaA box, these interactions can support, with reduced efficiency, DnaA dependent replication of plasmid R1. PMID- 1598214 TI - Analysis of nonuniformity in intron phase distribution. AB - The distribution of different intron groups with respect to phases has been analyzed. It has been established that group II introns and nuclear introns have a minimum frequency of phase 2 introns. Since the phase of introns is an extremely conservative measure the observed minimum reflects evolutionary processes. A sample of all known, group I introns was too small to provide a valid characteristic of their phase distribution. The findings observed for the unequal distribution of phases cannot be explained solely on the basis of the mobile properties of introns. One of the most likely explanations for this nonuniformity in the intron phase distribution is the process of exon shuffling. It is proposed that group II introns originated at the early stages of evolution and were involved in the process of exon shuffling. PMID- 1598215 TI - A two-dimensional YAC pooling strategy for library screening via STS and Alu-PCR methods. AB - We have developed a simple two-dimensional YAC pooling strategy to facilitate YAC library screening via STS and Alu-PCR approaches. The method has been implemented using the human total genomic YAC library of Olson and coworkers, and its validity tested by isolation of many chromosomes 19- and 21-specific YACs. The Alu-PCR approach is notable in that it is hybridization-based, such that PCR primer pairs do not need to be repeatedly synthesized and tested for each screening step. PMID- 1598216 TI - Bipartite structure of the downstream element of the mouse beta globin (major) poly(A) signal. AB - The downstream region of the mouse beta (major) globin poly(A) signal was mutated and analyzed for function in transfected COS cells. From analysis of unidirectional Bal31 deletions, the 3' boundary of the downstream element was defined as +22 (22 nucleotides downstream from the cleavage site). Analysis of cluster mutations, in which 5 or 6 adjacent bases were replaced with a random CA containing sequence in a manner that did not alter spacing, confirmed +22 as the 3' boundary of the downstream element. The analysis also revealed two short UG rich sequences, located from +5 to +10 and from +17 to +22, as major functional components. In contrast, a more refined series of mutations, in which clusters of 3 bases were replaced, failed to cause loss of function. We conclude that the downstream element of the mouse beta globin poly(A) signal is bipartite in structure, and that portions of its sequence are functionally redundant. PMID- 1598217 TI - Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells. AB - Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene. PMID- 1598219 TI - A seryl-tRNA synthetase gene is coamplified with the adenylate deaminase 2 gene in coformycin resistant Chinese hamster fibroblasts. PMID- 1598218 TI - Transcriptional activity of the human immunodeficiency virus-1 LTR promoter in fission yeast Schizosaccharomyces pombe. AB - We have analyzed the transcriptional activity of the human immunodeficiency virus type I (HIV-1) LTR promoter in the fission yeast Schizosaccharomyces pombe (S.pombe). The ability of a series of 5'-deleted forms of the HIV-1 LTR promoter to direct transcription of the chloramphenicol acetyltransferase reporter gene was studied. We found that the HIV-1 promoter is functional in S.pombe and that deletion of sequences upstream of the NF-kB binding site previously identified to contain the negative regulatory element (NRE) in mammalian cells, resulted in about thirty-fold increase in transcriptional activity. Sequences in the HIV-1 promoter that bind NF-kB were found to be essential for transcriptional activation in S.pombe. In mammalian cells, transactivation of the HIV-1 LTR requires TAR sequences and the viral Tat protein. In fission yeast, Tat failed to transactivate the HIV-1 LTR, suggesting that S.pombe may lack a cellular factor(s) required for the Tat transactivation process. PMID- 1598220 TI - Human cDNAs encoding elongation factor 1 gamma and the ribosomal protein L19. PMID- 1598221 TI - Nucleotide sequence of a cDNA encoding a Trypanosoma cruzi acidic ribosomal P1 type protein. PMID- 1598222 TI - The location and nucleotide sequence of the 5S rRNA gene of bunt of wheat, Tilletia caries and T. controversa. PMID- 1598223 TI - Variable regions of a human anti-DNA antibody O-81 possessing lupus nephritis associated idiotype. PMID- 1598224 TI - Sequence of Trypanosoma brucei tRNA genes encoding cytosolic tRNAs. PMID- 1598225 TI - Sequence of scs and scs' Drosophila DNA fragments with boundary function in the control of gene expression. PMID- 1598226 TI - Isolation and identification of restriction endonuclease, SelI from a cyanobacterium, Synechococcus elongatus. PMID- 1598227 TI - Optimization of the PCR program for RAPD analysis. PMID- 1598228 TI - New nucleotide sequence data on the EMBL File Server. PMID- 1598230 TI - Dinucleotide repeat polymorphism at the human CRYB2 gene locus (22q11.2). PMID- 1598229 TI - CTF4, a chicken transcription factor of the helix-loop-helix class A family. PMID- 1598231 TI - Molecular Probe Database: a database on synthetic oligonucleotides. AB - The Molecular Probe Data Base (MPDB) is designed to collect and make available on line information on synthetic oligonucleotides. This paper briefly describes the purpose of MPDB, its content and structure, forms and mode of data distribution, and a series of additional services available to scientists using MPDB. PMID- 1598232 TI - PROSITE: a dictionary of sites and patterns in proteins. PMID- 1598233 TI - The SWISS-PROT protein sequence data bank. PMID- 1598235 TI - GenBank. AB - The GenBank nucleotide sequence database now contains sequence data and associated annotation corresponding to 85,000,000 nucleotides in 67,000 entries from a total of 3,000 organisms. The input stream of data coming into the database is primarily as direct submissions from the scientific community on electronic media, with little or no data being keyboarded from the printed page by the databank staff. The data are maintained in a relational database management system and are made available in flatfile form through on-line access, and through various network and off-line computer-readable media. The data are also distributed in relational form through satellite copies at a number of institutions in the U.S. and elsewhere. In addition, GenBank provides the U.S. distribution center for the BIOSCI electronic bulletin board service. PMID- 1598236 TI - The EMBL Data Library. PMID- 1598237 TI - TFD: the transcription factors database. PMID- 1598234 TI - Haemophilia B: database of point mutations and short additions and deletions- third edition, 1992. PMID- 1598238 TI - Codon usage tabulated from the GenBank genetic sequence data. PMID- 1598239 TI - Compilation of DNA sequences of Escherichia coli (update 1992). AB - We have compiled the DNA sequence data for E. coli available from the GENBANK and EMBL data libraries and over a period of several years independently from the literature. This is the fourth listing replacing and increasing the former listings substantially. However, in order to save space this printed version contains DNA sequence information only, if they are publically available in electronic form. The complete compilation including a full set of genetic map data and the E. coli protein index can be obtained in machine readable form from the EMBL data library (ECD release 10) or from the CD-ROM version of this supplement issue directly. After deletion of all detected overlaps a total of 1,820,237 individual bp is found to be determined till the beginning of 1992. This corresponds to a total of 38.56% of the entire E. coli chromosome consisting of about 4,720 kbp. This number may actually be higher by some extra 2.5% derived from lysogenic bacteriophage lambda and various DNA sequences already received for other strains of E. coli. PMID- 1598240 TI - A comprehensive list of cloned human DNA sequences--1991 update. AB - An updated list of DNA sequences cloned from the human genome over the past year (1991) is presented. Intended as a guide to clone availability, this list includes published reports of cDNA, genomic and synthetic probes comprising both gene and pseudogene sequences. PMID- 1598241 TI - The Ribosomal Database Project. AB - The Ribosomal Database Project (RDP) complies ribosomal sequences and related data, and redistributes them in aligned and phylogenetically ordered form to its user community. It also offers various software packages for handling, analyzing and displaying sequences. In addition, the RDP offers (or will offer) certain analytic services. At present the project is in an intermediate stage of development. PMID- 1598242 TI - The GDB Human Genome Data Base Anno 1992. PMID- 1598243 TI - After the resolution. PMID- 1598244 TI - Hunter's ground. Interview by Janet Snell. PMID- 1598245 TI - Right to refusal. PMID- 1598246 TI - Complementary agenda. PMID- 1598247 TI - Health for generations. PMID- 1598248 TI - A shameful chapter. PMID- 1598249 TI - Man-made problems. PMID- 1598251 TI - Supply and demand. PMID- 1598252 TI - Bridging the distance. PMID- 1598250 TI - Number one priorities. PMID- 1598253 TI - Hidden nursing. PMID- 1598254 TI - Time for change. PMID- 1598256 TI - Predicting orientation of infant feeding. PMID- 1598255 TI - Heart of gold. Interview by Daloni Carlisle. PMID- 1598257 TI - Quality of care in a dermatological wards. PMID- 1598258 TI - Energy requirements and eating disorders. PMID- 1598259 TI - Care with conviction. PMID- 1598260 TI - Assessing trauma. PMID- 1598261 TI - Fighting depression. PMID- 1598263 TI - HIV rare in donations. PMID- 1598262 TI - Nutrition: hard to swallow. PMID- 1598264 TI - Open learning programme. M3: managing stress. Part (i). The stress question [continuing education credit]. PMID- 1598266 TI - The art of ageing. PMID- 1598265 TI - Response to HIV doctor issue. PMID- 1598267 TI - Epilepsy education. PMID- 1598268 TI - Incendiary words. PMID- 1598269 TI - Fit for the job. PMID- 1598271 TI - A very personal issue. PMID- 1598270 TI - Home economics. PMID- 1598272 TI - Fresh outlooks. Outpatient nursing. PMID- 1598273 TI - Common complaints. PMID- 1598274 TI - Serving outpatients. PMID- 1598276 TI - Seen but not heard. PMID- 1598275 TI - Sick kids' health ideas. Outpatient nursing. PMID- 1598277 TI - Bereavement care in an acute ward. PMID- 1598278 TI - For better or for worse: ward sisters. PMID- 1598279 TI - Does reality orientation work? PMID- 1598280 TI - Systems of life. Muscle 1. PMID- 1598281 TI - Where can I go? PMID- 1598283 TI - Learning disabilities. Annie's story. Interview by David Brandon. PMID- 1598282 TI - Infusion therapy. Internal delivery. PMID- 1598284 TI - Learning disabilities. A deficient solution. PMID- 1598285 TI - M4: assertiveness. Part (i): Assertiveness and nursing. PMID- 1598286 TI - HIV-positive surgeon case raises controversy. PMID- 1598287 TI - HIV-positive surgeon case raises controversy. PMID- 1598288 TI - Linking AIDS and family planning. PMID- 1598289 TI - Magic mixture. PMID- 1598291 TI - Systems failures. PMID- 1598290 TI - Finding out the worst. PMID- 1598292 TI - Ethical questions. PMID- 1598293 TI - Called to account. PMID- 1598294 TI - Five years' hard labour. PMID- 1598295 TI - Community care act. Gathering momentum. PMID- 1598296 TI - Community care act. All change. PMID- 1598298 TI - Theatre opportunities. PMID- 1598297 TI - No quarter to racists. PMID- 1598299 TI - A deadly combination. PMID- 1598301 TI - A bright future. PMID- 1598300 TI - Changing patterns of student nurse recruitment--2. AB - In 1970, a study was carried out to assess the type of information provided by schools of nursing to recruit prospective candidates to the profession. A follow up study in 1980 showed that some response had been made to suggestions about particular types of information that potential recruits required (see Part 1, April 29). This week, in Part 2, the changes that have taken place in information exchange between 1980 and 1990 are assessed. PMID- 1598302 TI - Come to Czechoslovakia. PMID- 1598303 TI - Courage in the face of crisis. PMID- 1598304 TI - Cancer--more than a star sign. PMID- 1598305 TI - Theories without thought? PMID- 1598307 TI - Working together. PMID- 1598306 TI - Unequal partners. PMID- 1598308 TI - Overdue celebration held for life of neglected Black leader. PMID- 1598310 TI - Introduction to immunology. AB - The immune system is a complex network of components functioning to provide host defense. This network consists of immunologic cells and their products (e.g., interleukins and colony-stimulating factors), organs, tissues, complement, and major histocompatibility complex antigens. These components are organized into specific and nonspecific immune systems, the major functional activities of which include antigen presentation and cell-mediated cytotoxicity. PMID- 1598309 TI - Hematopoiesis. AB - Hematopoiesis begins with the pluripotent stem cell in the marrow and culminates in mature, functional red blood cells, white blood cells, and platelets in the circulation. The process consists of a complex and well-orchestrated sequence of cell proliferation, differentiation, and maturation, that is stimulated and regulated by a host of cytokines and hormones. The various growth factors act individually and in concert at different stages of hematopoiesis and have important effects on mature cell function. PMID- 1598311 TI - Colony-stimulating factors: clinical applications. AB - Recombinant human colony-stimulating factors (CSFs) have potential for wide use in the areas of oncology and infectious disease. Granulocyte CSF and granulocyte macrophage CSF currently are approved for use in the treatment of neutropenia associated with standard-dose cancer chemotherapy and bone marrow transplantation, respectively. Other settings in which these agents have shown promise are dose-intensive chemotherapy, enhancement of progenitor cell support, primary and acquired neutropenias, myelodysplasia, aplastic anemia, and cytopenias associated with human immunodeficiency virus infection or myelosuppressive therapies for such infection or related conditions. Clinical findings in these areas are encouraging, and potential exists for additional applications of the CSFs. PMID- 1598312 TI - Pharmacokinetics and administration of colony-stimulating factors. AB - Granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony stimulating factor (GM-CSF) generally are rapidly eliminated from the blood after intermittent intravenous infusion. Subcutaneous administration of these agents results in lower peak concentrations but is associated with prolonged systemic exposure. Elimination of the factors appears to occur by several mechanisms, including white blood cell receptor-mediated endocytosis, metabolism by proteases, and urinary excretion by glomerular filtration with subsequent reabsorption and catabolism. The pattern and route of elimination are affected by type of factor and dosage, degree of glycosylation, renal function, and number of white blood cell receptors for the particular CSF. Granulocyte CSF and GM-CSF are approved for use in patients with nonmyeloid malignancy who are receiving myelosuppressive chemotherapy, and those undergoing high-dose chemotherapy and bone marrow transplantation, respectively. In these indications, treatment generally is initiated no earlier than 24 hours after chemotherapy and continued beyond the expected chemotherapy-associated neutrophil count nadir. Limited information suggests that subcutaneous administration is more effective than intermittent intravenous infusion. The latter may require the addition of albumin to ensure stability. Storage and handling guidelines include preventing exposure to extreme temperatures and avoiding excessive agitation of the solution. PMID- 1598313 TI - Strategic planning for the colony-stimulating factors. AB - The rapid development and emergence into the marketplace of therapeutic and diagnostic biotechnology products pose a considerable challenge to pharmacists, particularly in light of economic strictures wrought by changes in the health care field. At the same time, the pharmacy profession is moving to a position of greater involvement and responsibility in the clinical management of drug therapy. These changes mandate that pharmacists become strategic thinkers, capable of designing and implementing plans that can integrate biotechnology products into their institutions' practices in a way that both enhances patient care and maintains or promotes financial stability. A strategic plan model incorporating the components of environmental scanning and strategy formulation, implementation, and analysis can be applied to the recombinant colony-stimulating factors. PMID- 1598314 TI - Possible chemical pollution. PMID- 1598315 TI - Benefits of stress management groups. PMID- 1598316 TI - Viral hepatitis. PMID- 1598317 TI - Indications for MRI. PMID- 1598318 TI - The critical reading paper. PMID- 1598319 TI - Health promotion. PMID- 1598320 TI - In-patient and out-patient investigations. PMID- 1598321 TI - Referral decisions. PMID- 1598322 TI - The cholesterol debate. PMID- 1598323 TI - Is a salary option still taboo to GPs? PMID- 1598324 TI - A request for HRT. PMID- 1598325 TI - Management of uterine fibroids. PMID- 1598326 TI - Hypothyroid clinics. PMID- 1598327 TI - Women at work. PMID- 1598328 TI - Investigation of subfertility. PMID- 1598329 TI - The practice experience questionnaire. PMID- 1598330 TI - Better use of the ophthalmoscope. PMID- 1598331 TI - Assisted conception techniques. PMID- 1598332 TI - Recent advances in eye disease. PMID- 1598333 TI - Eye problems in the elderly. PMID- 1598334 TI - The eye in systemic disease. PMID- 1598335 TI - Helping visually handicapped people. PMID- 1598336 TI - Primary open-angle glaucoma. PMID- 1598338 TI - [The nursing approach to the venous disease patient in the immediate postoperative period]. PMID- 1598337 TI - Topical drug delivery. PMID- 1598339 TI - [Compulsory health treatment in psychiatry: the problems of interpretation]. PMID- 1598340 TI - [The companion of the heart or heartmate: an eye witness]. PMID- 1598341 TI - [The ambulatory monitoring of blood pressure]. PMID- 1598342 TI - [Epidemiological research on the health status of the elderly in Naples local health unit No. 41 in order to program and carry out health education interventions. Scuola Assistenti Sanitari--Italian Red Cross--Naples]. PMID- 1598343 TI - [The problems of nursing care directed at AIDS patients: nursing outside of hospital structures]. PMID- 1598344 TI - Violence to healthcare staff must be tackled nationally. PMID- 1598345 TI - Finding a model that fits. The use of nurse models in A&E. AB - Careful and promptly completed documentation is vital in A&E, where patients rarely stay for long. Most A&E departments do not appear to use a nursing model. Many respondents to the study felt there was no suitable model available for A&E. There is a need for more emphasis on developing models for A&E and educating nurses about their use; nurses also need to be actively involved in their implementation. PMID- 1598346 TI - A defence against the menopause. Uses and applications of hormone replacement therapy. AB - The menopause can result in a number of distressing short- and long-term symptoms. Hormone replacement therapy has been found to combat many of these symptoms. Research indicates that HRT is much safer today than the general public and many of the medical profession are led to believe. HRT is prescribed to far fewer women in the UK than in Europe or America. PMID- 1598347 TI - Grasping the marketing nettle. A professional development course for nurse practitioners in stoma care. AB - Effective management and efficient use of resources are prerequisites for a high quality service. Marketing skills are now essential for nurses. These consist of nurses being able to prove they can offer an economically viable service and to argue the case for more resources. Regular use of patient questionnaires will elicit opinions on standards of care. The health service's biggest resource is its staff: improving channels of communication and creating areas of accountability will fulfil its potential. PMID- 1598348 TI - Which infusate do I need? Physiological basis of fluid therapy. AB - A variety of infusates are used, and it is important that the consequences of overinfusion are understood. Infusates are used to expand the intravascular volume or to influence solute composition of body fluids. Choice of infusate depends upon the underlying physiological disturbances. The basis of infusate choice, the actions of frequently-used infusates and the consequences are outlined. PMID- 1598349 TI - Innovative treatment or ethical headache? Fetal transplantation in Parkinson's disease. AB - Current drug therapies have limitations in controlling Parkinson's disease in the long term. Early results of fetal cell transplantation are encouraging, suggesting it may help many sufferers. The technique raises ethical considerations, particularly with regard to collection of fetal tissue. Nurses must form their own opinions on the technique, and while they may opt out of the actual operations involved, they still have a duty of care to these patients. PMID- 1598351 TI - Caring for HIV positive neonates. PMID- 1598350 TI - Caring for HIV positive neonates. PMID- 1598352 TI - Malaria--an old challenge in a modern age. AB - The incidence of malaria is increasing worldwide, and has reemerged in some areas where it was previously eradicated. The importance of full compliance with prophylactic medication must be stressed to travellers. Although aware of malarial symptoms, most travellers do not consult a doctor as soon as they appear. Health education about malaria represent a key area of occupational nurses' role. PMID- 1598353 TI - Creating an agenda for change. Quality assurance in mental health services. AB - Quality assurance is traditionally viewed in terms of structure, process and outcome, but ignores the fact that they coexist in day-to-day practice. Many quality assurance initiatives are based on the belief that organisational systems can be periodically improved using external experts; this can lead to a disjointed approach and alienate staff. QUARTZ is a quality assurance programme for mental health services, and encourages a collaborative, problem-solving approach among staff. Ongoing evaluation is essential to facilitate long-term change. PMID- 1598354 TI - How much do they want to know? Communicating with dying patients. AB - Many healthcare professionals either feel too inhibited to talk about death to a dying patient or consider that it will undermine wellbeing. Experienced nurses can help prepare and support staff when communicating with dying people. Patients may indicate that they wish to talk about their prognosis and treatment, and nurses must be able to detect verbal and non-verbal cues. Nurses can enhance the multi-disciplinary team by providing access to accurate and up-to-date information about patients; they can also act as patients' advocate. PMID- 1598355 TI - Stroke advisers may improve community services. PMID- 1598356 TI - Pointing to the way ahead. Health education for people with learning disabilities. AB - People with learning disabilities have a right to health education, and nurses working with them have ample opportunities to fulfil this role. Health education must cater for individual clients' needs, and be presented in a style and language they can easily understand. Effective communication partly depends on being able to emphasize with clients; it is important to appreciate that clients are responsible for their actions. PMID- 1598357 TI - Wound dressings on FP10 and GP10. AB - Although the full range of wound care products is not available in the community, new items are slowly being added to the list. Nurses have a responsibility to keep up-to-date with developments, particularly since nurse prescribing is imminent. Manufacturers' literature should be read frequently to keep up-to-date with additions and amendments. PMID- 1598358 TI - Creativity can move mountains. PMID- 1598359 TI - Retention of massed vs distributed response-prevention treatments in rats and a revised training procedure. AB - Two experiments were conducted to estimate the retention of response-prevention effects using massed vs distributed treatments in a model of animal avoidance learning. In Exp. I, 120 rats were trained to avoid shock in a one-way platform avoidance apparatus. Groups received response-prevention treatment or nontreatment in a 36-min. massed session or in several sessions distributed over a four-day period. In Exp. II, 160 rats were given two trials of escape training in a one-way shuttle box. Groups received response-prevention treatment or nontreatment in a 24-min. session of massed or distributed treatments delivered in one day. Subjects in both studies were tested using a passive-avoidance paradigm immediately following treatment, 24 hours later, and 30 days later. Analysis showed that response-prevention treatments were effective in reducing avoidance behavior and there were no significant differences in retention of avoidance associated with massed vs distributed response-prevention treatments. Implications for animals and humans are discussed, and researchers are encouraged to change from a criterion training procedure to an escape procedure since the latter is a closer analogue to the human condition. PMID- 1598360 TI - The Wisdom Group: a psychotherapeutic model for elderly persons. AB - This article describes the "Wisdom Group," a therapy devised for the psychotherapeutic treatment of elderly persons. Preliminary work was done with five men of advanced age who were psychiatric in-patients with diagnoses of organicity and depression. The approach was effective in eliciting interaction during the meetings with each other and the group leader. The potential use of this intervention with a greater variety of elderly persons is discussed. PMID- 1598362 TI - Menninger's motives for suicide in the notes of completed and attempted suicides. AB - Brevard, Lester, and Yang in 1990, studying Menninger's motives for suicide, reported more evidence for the wish to be killed (i.e., self-blame or self punishment) in suicide notes for completed suicides than in parasuicide notes for attempted suicide; however, they did not control for age and sex. A comparison of notes written by completed and attempted suicides that controlled for age and sex showed no differences in the presence of content which reflected Menninger's three motives for suicide, including the wish to be killed. PMID- 1598361 TI - Depression in elderly persons and its correlates in family practice: a Canadian study. AB - Depression was studied in a Canadian community sample of 582 men and 906 women over the age of 65 years. The Center for Epidemiological Studies Depression Scale (CES-D) provided the measure of depressive symptomatology. The Diagnostic Interview Schedule was used to confirm clinical diagnosis. A total of 8% of the sample (4.3% of men and 10.4% of women) were at or above the cut-off point of 16 on the Depression Scale. Significant Pearson correlations with depression were found for gender and education. The married and never married persons showed low depression while the widowed, separated, or divorced appeared to be at high risk. The relationship of marital status to depression is primarily a woman's issue as most elderly men are married. This finding may have implications for policy and program planning for this population. PMID- 1598364 TI - Correlation between humorous coping style and health. AB - A significant correlation of -0.34 was found between scores on the Situational Humor Response Questionnaire and a measure of perceived physical health for 51 college students. Mean scores on the questionnaire were similar to those of the original standardization population. PMID- 1598363 TI - Topic control as relational control and its effect on the outcome of therapy. AB - The concept of relational control was measured using the index of Topic Control to investigate Haley's assertion that successful therapy is characterized by the therapist controlling the definition of the therapeutic relationship and defining it as a complementary relationship in which the therapist is in a "one-up'' position. Following Haley's assertion, it was hypothesized that: (a) across a sample of successful therapeutic dyads, therapists exhibit a greater measure of Topic Control than clients; (b) across a sample of successful and unsuccessful therapists, successful therapists exhibit a greater measure of Topic Control than unsuccessful therapists; (c) across a sample of successful and unsuccessful clients, unsuccessful clients exhibit a greater measure of Topic Control than successful clients; and (d) across a sample of unsuccessful therapeutic dyads, clients exhibit a greater measure of Topic Control than therapists. Analysis of therapist-client transactions for Topic Control was conducted by trained raters across 18 full-case transcripts of actual therapy interviews. The same transcripts were also analyzed by trained raters with respect to clients' change over the course of treatment. The results did not support the notion that across successful dyads therapists exhibit a greater measure of Topic Control than clients; and they did not support the hypothesis that across successful and unsuccessful therapists, successful therapists exhibit a greater measure of Topic Control. Also, there was no support to show that across successful and unsuccessful clients, unsuccessful clients exhibit a greater measure of Topic Control. Finally, the results did not support that across unsuccessful dyads, clients exhibit greater Topic Control than therapists. PMID- 1598365 TI - Comparison of dream content of depressed vs nondepressed dreamers. AB - Dreams of 20 college women classified as depressed by scores on the Beck Depression Inventory were compared with those of 21 nondepressed college women. The depressed group recalled fewer dreams, had significantly shorter dream length, and displayed less anger in their dreams. They also had fewer characters in their dreams and especially fewer strangers. PMID- 1598367 TI - Rubinstein-Taybi syndrome. AB - Rubinstein-Taybi Syndrome was first described in 1957 but only in 1963 as a distinguishable type of moderate mental retardation. The cause is still unknown although some type of genetic origin is possible. No consistent chromosomal abnormality has been demonstrated, the chromosomal analysis is normal, and cases are generally not considered hereditary. The recurrent risk for siblings is approximately 0.1% but may be as high as 50% for offspring of patients with the syndrome. The Rubinstein-Taybi syndrome is not at present detectable before birth and is evenly found in both males and females. The syndrome was thought to be rare but an increase in the number of reported cases each year suggests it is not as rare as estimated. It is thought to occur in about 1 in 300,000 births, and since it has become readily identifiable, more than 400 cases have been reported worldwide. PMID- 1598366 TI - Needs (Murray, 1938) and state-variables (Skinner, 1938). AB - Skinner's concept of drive as a state-variable and his powerful rationale for introducing it agree closely with Murray's treatment of need. Operant behaviorists' usual deprecation of motivation in favor of stimulus control arises partly from features of parameters, insufficiently explored in some regions, of Skinner box research. For human adults on rich reinforcement schedules, response selection is chiefly controlled by the regnant motive. Skinner's life-long interest in inner events and translating psychodynamic concepts into behaviorese was obscured by his metalanguage philosophy of science (behaviorism). PMID- 1598368 TI - Religious sentiment in church affiliates and nonaffiliates. AB - The Religious Life Inventory was administered to 454 college students, members of one of three religious denominations (Catholic, Methodist, Baptist) or a member of no church (nonaffiliate). An evaluation of the four groups on 3 scales showed nonaffiliates scored less external in religious sentiment than affiliates, Baptists scored higher on internal religious sentiment than nonaffiliates, and no differences among groups were found for interactional religious sentiment. PMID- 1598369 TI - Depression, suicide ideation, and aggression among high school students whose parents are divorced and use alcohol at home. AB - 106 high school students from a small rural high school completed the Children of Alcoholics Scale, Zaks and Walters' Aggression Scale, Beck Depression Scale, and a modified version of the Beck Scale of Suicide Ideation. Analyses of variance showed boys were not experiencing suicide ideation any more than girls; suicide ideation was similar across the four grades, but on aggression alcohol-dependent boys scored significantly higher than girls, and in Grade 9 boys' scores were significantly higher than those in Grade 10. The sophomores' scores on alcohol dependency were significantly lower than the freshmen's scores. Boys and children from divorced homes had higher scores on aggression than girls and children from nondivorced homes. Children from homes in which alcohol was used had higher depression scores than children from nonalcoholic homes. Freshman girls and sophomore boys had higher depression scores than senior boys and girls. A Pearson r of 0.28 between scores on alcohol dependency and suicide ideation was significant, but research is needed to understand better the associations of thoughts of suicide and drug-alcohol dependency among these high school students so strategies for prevention and intervention can be focused. PMID- 1598371 TI - Prisoners and locus of control: initial assessments of a specific scale. AB - The relatively few studies conducted with prisoners' locus of control suggest an important relationship between locus of control and prisoners' adjustment. However, one obstacle to further development of this knowledge is lack of appropriate measurement. This paper is an account of initial assessments conducted with a locus of control measure specific to the prison environment. All tests support the reliability and validity of the scale. Results of the assessments also indicate changes which should be made to improve the psychometric properties of the scale. Further assessments will need to be conducted after the instrument is revised. Use of the Prison Locus of Control scale should facilitate and lend accuracy to research with prisoners. The scale items are provided. PMID- 1598370 TI - Comparison of the Hamilton Depression Rating Scale and the Geriatric Depression Scale: detection of depression in dementia patients. AB - The present longitudinal prospective study compared results from the Geriatric Depression Scale with those from the Hamilton Depression Rating Scale for 30 dementia patients. The criterion measure was presence of depression as indicated by the psychiatric diagnosis. The psychiatrist and physician's assistant made the Hamilton ratings while the psychology staff administered the Geriatric Depression Scale. The two measures were statistically unrelated from Times 1 and 2 (rs = .26 and .41). Eleven (37%) patients were depressed and nine received antidepressant medications. Sensitivity ratings were 82% and 9%, respectively, and specificity ratings were 88% and 92%, respectively. Possible explanations for the success of the Geriatric Depression Scale and lack of success of the Hamilton ratings in detecting depression in this population are discussed. PMID- 1598372 TI - Changes in smoking legislation, attitudes, and behavior. AB - Legislative changes and attitude campaigns are generally acknowledged to be effective in the battle against smoking and its health hazards. In some instances it seems as if these means are insufficient to produce necessary change. In this study, the following general hypotheses were posed: (1) an advertising ban leads to reduced tobacco sale and (2) to reduced smoking; (3) attitude campaigns improve attitudes about regulation of smoking and (4) reduce smoking. In addition, two national hypotheses were formulated. The results supported neither hypothesis! It is concluded that it is important to follow the development closely with scientific methods of high quality. Further, smoking campaigns must include a broad spectrum of interventions to be sufficiently effective. PMID- 1598373 TI - A measure of overt self-criticism: validation and correlates. AB - A measure of overt self-criticism was constructed and validated for 38 high and low scorers out of 300 undergraduates, using reports by knowledgeable others. PMID- 1598374 TI - Assessing the likelihood of reliable workplace behavior: further contributions to the validation of the Employee Reliability Inventory. AB - This paper summarizes a number of studies in which the validity of the Employee Reliability Inventory, a preemployment screening instrument designed to assess the likelihood of reliable and productive workplace behavior, was examined. Criterion-related studies compared the scores of a broadly diverse group of job applicants with those obtained from an array of criterion and comparison groups, for whom there was documented evidence of reliable or unreliable behavior. Criterion-related evidence indicates that the six scales are effective in differentiating a variety of criterion groups with unreliable behavior from a number of different job applicant comparison groups. Construct-related evidence for the validity of an emotional adjustment scale is reported as well. The issue of response distortion in preemployment inventories is discussed, and data are reported which indicate that scores on all six scales appear to be functionally free from the potentially confounding effects of response distortion. These results are consistent with the original validation and cross-validation findings, which supported the validity of the six scales when assessing the likelihood of reliable behavior in a population of job applicants. PMID- 1598375 TI - The role of just world belief and anger issues in self-defeating personality. AB - Persons who scored higher on a measure of self-defeating personality did not believe in a just world as implied in the writings of such theorists as Reik (1941); however, they had a greater awareness of anger and feelings of mistrust and suspiciousness of others, held anger in, and were self-critical. These latter findings are consistent with conclusions regarding masochism proposed in 1991 by Glickauf-Hughes and Wells. PMID- 1598376 TI - Contributions to psychohistory: XIX. Kamikaze pilots: the Japanese versus the American perspective. AB - Semantic differential ratings of Kamikaze pilots by 90 Japanese and 57 American subjects are contrasted. The observed differences are interpreted within the context of Hasegawa's phenomenological analysis of contemporary Japanese society. PMID- 1598377 TI - Operant conditioning of activities of daily living on a psychogeriatric ward: a simple method. AB - On a psychogeriatric ward a simple token economy was established by handing out coffee and cigarette tickets for demands of concrete Activities of Daily Living from 14 men and 16 women. During the treatment period the number of target behaviors increased dramatically and many positive spin-off effects were observed. It was concluded that simple token economies of even 18 weeks can easily be introduced and administered and produce decisive positive changes with respect to psychogeriatric patients' activities of daily living, staff attitudes, and ward atmosphere. PMID- 1598378 TI - The MOS Short-Form General Health Survey: single item vs multiple measures of health-related quality of life: some nuances. AB - Researchers concluded that Item 2 of the Short-form General Health Survey of the Medical Outcomes Study can be used as a single-item measure of health-related quality of life. This conclusion is tested again on a random sample of elderly people in the Netherlands. Although it can be concluded that the psychometric properties of the short form are satisfactory, the use of the single item as a measure of health-related quality of life is discussed. PMID- 1598379 TI - If Freud's theory be true.... AB - If Freud's theory of defense and repression is true, it is proposed that the manifest content of his conscious thought (his theory) would not accurately represent his real thoughts. It would rather distort, disguise, and hide them. Freud's own special method of analysis and interpretation, which rejects the manifest meaning of conscious thought, would have to be used to gain insight into his "real,'' but still hidden, thoughts. Wherever Freud's manifest thoughts, rather than his real thoughts, have shaped subsequent theories of therapy and clinical practice, re-appraisal of these later theories and practices is recommended. Resolving this misunderstanding of Freud's thought may facilitate integration of clinical theory. PMID- 1598380 TI - Correlations of Beck Depression Inventory and Reynolds Adolescent Depression Scale. AB - The scores of 15 adolescents who had a primary diagnosis of Posttraumatic Stress Disorder, 21 of Conduct Disorder, and 23 control subjects on the Beck and Reynolds depression scales were correlated .58 over-all, .73 for the Posttraumatic group, .48 for the Conduct Disordered group, but .37 for controls. The Reynolds scale did not identify depression in these adolescents as effectively as did the Beck scale. PMID- 1598381 TI - University students' felt alienation and their attitudes toward African Americans, women and homosexuals. AB - 177 respondents attending a midwestern state university reported greater alienation from the wider society when they held more positive attitudes than negative ones toward women and homosexuals. Alienation and attitudes toward African-Americans, women, and homosexuals were not influenced by gender or religiosity. PMID- 1598382 TI - Psychometric properties of Bradburn's Affect Balance Scale among elderly persons. AB - Some psychometric properties of the Affect Balance Scale have been tested on a random sample of 354 elderly people in the Netherlands. Internal reliability estimates were comparable with prior ones, and the 8-wk. test-retest reliability is reasonable for these 5-item measures. PMID- 1598384 TI - Evaluation strategies for some nonstandard conditionals during adolescence. AB - 380 adolescents and young adults between the ages of 11 and 29 years participated in three experiments in which they were asked to evaluate both universally quantified nonstandard and standard conditionals using items of information bearing upon them. Subjects found it much easier to avoid a biconditional interpretation with the nonstandard than with the standard conditionals, which throws doubt on the explanation of desire for symmetry of biconditional conversion. It was argued, from data of other studies, that a modified version of the Piagetian view that biconditional conversion occurs as a result of a desire to avoid the complications of dealing with three factors explains most cases of such conversion in adolescence. Results also confirmed that it is more profitable to analyse performance on tasks of this kind using a two-stage model of interpretation and information use previously developed to explain performance with standard universally quantified conditionals than to view such tasks as providing truth-table values. Such an analysis was extended to the nonstandard conditionals studied in the present paper. The origins of the dramatic differences in information-use strategies adopted by adolescents for standard and nonstandard conditionals remain unclear. PMID- 1598383 TI - Externalization as a self-protective mechanism in a stigmatized group. AB - The Nowicki-Strickland measure of internal-external locus of control was administered to 110 African-American adolescents. Analysis indicated high externalization, even though these students had a higher than average self concept. PMID- 1598386 TI - Gilles de la Tourette syndrome in India: two cases. AB - Two cases of Gilles de la Tourette syndrome from India are presented. The symptomatology of Tourette syndrome is the same as that documented in western populations which suggests biological factors in the aetiology of the syndrome. PMID- 1598385 TI - Mortality rates and aggression management among Native Americans. AB - Using data from the general USA population, Field reported that various causes of death correlated with measures of aggression management obtained from suicide and homicide rates. Since in this study replication of these findings cross culturally was not successful with data for US Indian Health Service areas and Field did not explain his ecological correlations, the reliability and validity of his findings may be questioned. PMID- 1598387 TI - The psychiatrist as shaman: Sullivan and schizophrenia. AB - This paper describes an analogy between the primitive shaman's emotional illness, and its control, and the schizophrenic episodes of Harry Stack Sullivan, the founder of the interpersonal school of psychiatry. Like the primitive shaman, Sullivan partially overcame his illnesses, drawing from his psychoses the insights through which he healed others. PMID- 1598388 TI - [An assessment of the permissible level of a mixture of radionuclides from the Chernobyl fallout in human lungs]. AB - The permissible level of a radionuclide mixture, resulted from the Chernobyl burst, in the human being lungs was determined for two kinds of compounds: absolutely insoluble compounds and soluble compounds in the state of equilibrium. For this purpose the data were used concerning the radionuclide composition and aerosol disperse in lower atmosphere which were obtained by the Department for Dosimetric Control (NPO "Pripiat'"). The results of measurements of 137Cs content taken by the use of human radiation spectrometer (HRS) needed an adequate estimation: low level of 137Cs in the human lungs and body within the Chernobyl NPP, zone does not guarantee radiation security. The notion "permissible content" and the possibility of using thereof in the individual dosimetric control are discussed. PMID- 1598390 TI - [The radiation modification of the sugar fragment in DNA: the formation of breaks, a change in polymer conformation and the transfer of the damage to the base]. AB - Comparative analysis of the author's own data and data reported in the literature on the nature of the intermediate and end molecular products of radiolysis of DNA, its precursors and substances stimulating certain DNA fragments, allows to attribute the formation of breaks and alkaline-labile sites in DNA strands and changes in the polymer conformation, to the formation and transformations of some types of primary radicals of the sugar fragment. In order to explain certain effects induced by irradiation of DNA and its precursors (a balance of basic products of radiation destruction of DNA and ESR data concerning low temperature radiolysis of bases, nucleotides and nucleosides) the author proposes a model of the transfer of a damage (free valence) from 2-deoxyribosyl to a base within one nucleotide. PMID- 1598389 TI - [The kinetics of the chemical modification of DNA radiation transformations in multicomponent systems. An analytical review]. AB - Most probable ways of chemical protection and sensitization of DNA macromolecules under the effect of ionizing radiation in aqueous solutions have been investigated. A kinetic model in proposed, based on the experimental data available, that consists of 25 reactions involving DNA (D), protein (P), glutathione (G), oxygen (O2), various protectors and sensitizers (A), active products of water radiolysis (O, e (H)), free and peroxide radicals of DNA and other components, and peroxides. General and partial rates of radiation transformations of DNA, depending on D, P, G, O2 and A concentrations are expressed in analytical terms. The relationships obtained are used for a qualitative description of some biological effects of ionizing radiation that is: a difference in radiosensitivity of different organs and tissues and its alteration during the cell cycle; oxygen effect; and the concentration relationships of the radioprotection and radiosensitization coefficients. PMID- 1598392 TI - [The effect of He-Ne laser radiation on the survival of HeLa cells subjected to ionizing radiation]. AB - A monolayer of HeLa cells, at the stationary phase of growth, exposed to He-Ne laser radiation (632.8 nm; 100 J/m2) either 5 min or 60 min prior to gamma irradiation (0.1-10 Gy; 6.75 Gy/min), or 5 min after irradiation has been investigated. With a 5-min interval between irradiation sessions (both sequences) the survival curves are virtually the same as those for gamma-irradiated cells only. With He-Ne laser radiation delivered 60 min before gamma irradiation with doses exceeding 5 Gy, a fraction of radioresistant cells is identified whose D0 is almost twice as high as D0 of basic cell mass (3.6 and 1.7 Gy respectively. The survival curve becomes a two-component one. A hypothesis is proposed that He Ne laser radiation activates, in some cells, the processes that promote the repair of radiation damages. PMID- 1598391 TI - [Changes in the radiosensitivity of cortical thymocytes during differentiation]. AB - To determine the radiosensitivity of cortical thymocytes at different stages of their differentiation, that took three days, estimated was the part of DNA of labelled thymocytes within the salt soluble fragments of the chromatin formed 6 h after irradiation of rats at different times during three days following the initial labelling of thymic blast DNA. The radiosensitivity of cells, which were at the terminal stages of differentiation, was twice as high as that of lymphocytes which were at the initial stage of differentiation. PMID- 1598393 TI - [The radiosensitivity of hematopoietic stem cells from mice forming splenic colonies after 8 and 12 days following bone marrow cell transplantation (CFU-S-8 and CFU-S-12)]. AB - The method of "macro-" and "microcolonies" was used to study the radiosensitivity of CFU-S that form "early" (8 days) and "late" (12 days) splenic colonies after transplantation of syngeneic bone marrow to fatally exposed mice: no significant differences were found. Median lethal doses (D0) for CFU-S-8 and CFU-S-12 were 1.03 and 1.13 Gy for "microtest" and 0.99 and 1.16 Gy for "microtest" respectively. PMID- 1598395 TI - [The mechanisms of lymphoid regulation and the radiosensitivity of the hematopoietic system]. AB - On the basis of the authors' own data and the literature it has been inferred that the key principles of the haemopoietic system regulation are similar to those of the immune system. The cells of a lymphoid origin are found, which implement helper and suppressor functions with respect to early haemopoiesis precursors; the influence of lymphokines on this compartment under the effect of radiation is described. Disturbances in the haemopoiesis system regulation, that result from various damaging effects, might be corrected by T-lymphocytes and lymphokines. The data obtained suggest that the formation of splenic colonies is the result of the interaction of some cell populations. That is why many radiobiological characteristics of CFUs may be attributed to partner cells (for instance, T-lymphocytes). PMID- 1598394 TI - [The effect of pectin and pectin-containing products on the metabolic indices of the blood and liver tissue of rats subjected to external gamma irradiation]. PMID- 1598397 TI - [The triboluminescence of the blood and the brain cellular elements in rats exposed to X irradiation in doses causing bone marrow, intestinal and cerebral syndromes]. AB - Triboluminescence of blood and brain cells (neurons and neuroglia) in bone marrow, intestinal and cerebral radiation syndromes has been investigated. Dynamics of triboluminescence intensity of neurons and glial cells after irradiation (0.013, 0.31 and 3.87 C/kg) is the same with that of blood triboluminescence. PMID- 1598398 TI - [Laser correlation spectroscopy of the blood serum--a new approach to the identification of groups at risk for specific diseases and poisonings in areas of ecological anomalies]. AB - The technique methodology of nuclear correction spectroscopy are proposed to solve the tasks of mass medico-biological examinations. From the analysis of 2500 LCS-spectra of blood serum of donors, from various nosologic groups, it is concluded that the LCS method permits to identify risk groups with respect to certain diseases and intoxications, as well as to study pathological processes and to prognosticate the efficacy of the therapeutic measures used. PMID- 1598399 TI - [The reaction of rat blood plasma to gamma radiation studied by the use of laser photon-correlation spectroscopy]. AB - Using the method of laser photon correlation spectroscopy it was shown that the typical pattern of distribution of blood plasma (BP) particles according to their sizes, characteristic of intact animals, was asymmetric with regard to a mean value. Gamma irradiation with sublethal doses was shown to change essentially the pattern of BP distribution. For instance, in BP of exposed animals, the number of particles of much smaller sizes increased as compared to that in intact animals. The smaller BP particle size was not the result of the direct effect of radiation on the blood. The in vitro irradiation of BP with various doses results usually in a considerable growth of particle sizes. PMID- 1598396 TI - [The stimulation of postradiation thrombocytopoiesis by low-intensity laser radiation]. AB - In experiments with gamma-irradiated (LD50/30) F1(CBA x C57Bl) hybrid mice, thrombocytopoietic effect of low-intensity laser radiation has been detected. The data obtained may be used in developing modes of haemopoiesis stimulation in a gamma-irradiated organism. PMID- 1598400 TI - [An experimental study of the amides of aromatic carboxylic acids as radiosensitizing agents]. AB - In experiments with mice a study was made of the radiosensitizing efficacy of 10 aromatic carbonic acid amides, benzene, naphthalene, pyridine and quinoline derivatives. It has been found, for this group of substances, that there is a direct correlation between the ability of the substance to reduce the splenic endocolonies production and the inhibitory activity with regard to poly(ADP ribose) polymerase of thymocyte nuclei. Within the group of substances under study, new agents are found and described and new relationships are revealed between their chemical structure and biological activity. PMID- 1598401 TI - [The effect of a plantain preparation on the efficacy of the irradiation of experimental animals with tumors]. PMID- 1598402 TI - [The reproductive capacity of male mice protected against the superlethal action of gamma radiation by the administration of a mixture of Archangelica officinalis and Ledum palustre extracts]. AB - Thirty-day old albino mongrel male mice were exposed to gamma radiation (LD90/30) after preventive single injection of a mixture of extracts from Archangelica officinalis and Ledum palustre. One month after irradiation, the survivors were mated to nonirradiated females. Healthy offspring were obtained from 11 out 12 experimental males. The number of mouse pups was 10.2 +/- 0.6 and 7.4 +/- 0.7 in the experimental and nonirradiated groups respectively. The number of both sexes in the posterity of nonirradiated parents was equal, whereas in offspring of experimental groups, the number of female pups was 2.3 times larger than that of males. The experimental posterity was found to be resistant to supralethal radiation doses. PMID- 1598403 TI - [The importance of removing quinoid radiotoxins from the irradiated organism in the efficacy of hemosorption in the therapy of radiation sickness]. AB - Sorption by SKN-2M coal of various endogenous substances, including quinones (tyrosine oxidation products) and quinoid radiotoxins (QR) isolated from gamma irradiated plant and animal tissues has been studied. The fact that the precursors of QR-DOPA, tyrosine and QR, isolated from gamma-irradiated plant and animal tissues, are readily absorbed by the sorbent under study supports the major contribution of QR removal from the organism to the therapeutic effect of hemosorption after gamma irradiation of animals with minimal lethal doses. PMID- 1598404 TI - [The localization of radioactive cesium in bovine muscle tissue]. AB - The form in which radioactive caesium is present in muscular tissue has been investigated. It has been found that protein agents under study do not form stable complexes with radioactive caesium. It is suggested that caesium-137 is partially bound by muscular cell membranes upon meet storage. PMID- 1598405 TI - [The specificity of the deposition of intratracheally administered plutonium in different skeletal bones with a change in iron homeostasis]. AB - A study was made of the distribution of plutonium-239 injected intratracheally within different bones of the skeleton, the iron status in the blood being changed. The iron preparation caused a 2.5-3-fold decrease in the plutonium loading onto cancellous bone tissue that displayed, in ordinary conditions, a higher tropism to the radionuclide than a cortical highly mineralized bone did. PMID- 1598408 TI - [The current situation of radiologic diagnosis of blood vessels]. AB - The current situation with regard to vascular diagnostics in West Germany is analyzed on the basis of the results of a survey of large non-university institutes of radiodiagnostics. The operative equipment present is generally appraised as being adequate. However, equipment for the performance of digital subtraction angiography must be available. The importance of the intravenous technique is clearly diminishing. In some cases, large-format angiograms are completely dispensed with. The frequency of angiography is greatly decreasing. The expenditure of time and effort for the individual investigation has become greater, so that the angiographic equipment and rooms are used to a much greater extent in terms of time. A fairly uniform observation was that about 60% of all arteriographies are necessary because of sclerotic vascular conditions (AOD). These are often combined with interventional measures. The arteriographies are mainly carried out in the lower limbs (50-70%). The remainder is distributed in thoracic and, in particular, abdominal angiographies, among which the renovasographies still predominate. Numerous leg phlebographies are carried out everywhere and account for 85-95% of all venographic investigations. There has been a great decline in lymphographies throughout Germany. PMID- 1598407 TI - [The methods of irradiation dose fractionation and rate change used in studying the capacity for the postradiation repair of CFU-s forming splenic colonies after 8 and 12 days following bone marrow cell transplantation]. AB - The method of dose fractionation and decreasing the dose-rate using "macro-" and "microcolonies" techniques was used to study the ability of CFU-S-8 and CFU-S-12 to repair sublethal radiation damages after irradiation thereof within the bodies of bone-marrow donors and recipients. A more committed CFU-S-8 population was found to surpass a younger and less committed CFU-S-12 population with respect to their repairability. PMID- 1598406 TI - [A comparative evaluation of the changes in the duration of "hexenal sleep" in acute radiation and combined radiation-thermal lesions]. AB - In experiments with Wistar rats it was found that the increase in the length of the "hexenal dream" during the first week after the effect of a mixture of radiation and heat is much more pronounced than that observed after exposure to radiation alone and independent of the severity of a radiation component (gamma radiation, 4, 6 and 7.5 Gy). The peculiarities revealed in the hypnotic effect of hexenal develop against the background of the postirradiation aggravation of hypoalbuminemia and decrease in the liver ATP. PMID- 1598409 TI - [Diagnostic procedures in acute gastrointestinal hemorrhage]. AB - In gastrointestinal bleeding, the diagnosis is predominantly made by endoscopy. However, if the bleeding site is in a part of the intestine that cannot be reached by endoscopy, than the diagnosis is based on radiological and scintigraphic methods. In the past 5 years 35 patients with such cases of gastrointestinal bleeding had angiography and/or scintigraphy (n = 15) in our department. Based on our retrospective study of those cases, we advocate a management protocol for such patients based on the hemodynamic presentation. PMID- 1598411 TI - [Techniques and current indications for MR angiography]. PMID- 1598410 TI - [Angiography of the mesenteric artery 1976 to 1991. A change in the indications during mesenteric circulatory disorders?]. AB - While the mortality rate in patients with acute vascular mesenteric insufficiency is extremely high when angiography is not performed, it can be lowered by consistent angiographic examination. In a period of 16 years, 62 patients were investigated by angiography. A primarily vascular mechanism had caused the condition in 59 patients. In 25 cases arterial embolism was found, in 11 cases arterial thrombosis, in 3, venous thrombosis, and in 20 cases non-occlusive mesenteric ischemia was present. The mortality was 53%. Thus angiography is indicated whenever there is any suspicion of a mesenteric vascular disorder. PMID- 1598412 TI - [Delayed adverse reactions following the intravascular administration of a nonionic x-ray contrast medium]. AB - Side effects experienced by patients up to 7 days after intravasal administration of nonionic contrast media were recorded with the help of questionnaires. These were completed by the patients themselves and compared with data recorded in patients examined without the use of contrast media. Of the 1000 questionnaires distributed, 499 were returned (271 in the contrast media group, 228 in the other group). A statistically significant difference between the two groups was found with regard to local pain at the injection site. The reactions correlated with the time of intervention. Another significant side effect was found in increased diuresis, which did not lessen during the 7 days of our survey. Increasing side effects were noted with higher contrast medium dosage and advancing age. PMID- 1598413 TI - [A malignant mesothelioma of the peritoneum following radiotherapy. A case report]. AB - A 49-year-old woman developed ascites 31 years after radiation therapy for ovarian cancer and was admitted to hospital 1 year later. Diffuse infiltration of both sheets of the peritoneum was found by CT, which on histological investigation turned out to be an advanced malignant peritoneal carcinoma. When there is a history of radiation exposure, malignant peritoneal mesothelioma should be considered as the cause of ascites. PMID- 1598414 TI - [Non-Hodgkin's lymphoma of the hand. A case study and a comparison of imaging techniques]. AB - A pediatric patient with a Non-Hodgkin lymphoma of the hand is presented and the evidence of the different imaging modalities is discussed. Concerning the diagnostic information the Magnetic Resonance Imaging (MRI) proved to be superior to conventional radiographs and bone scan. Additionally MRI with Gd-DTPA significantly improved the follow up in this patient. PMID- 1598415 TI - [Reproducibility of bone density measurements of the distal radius using a high resolution special scanner for peripheral quantitative computed tomography (Single Energy PQCT)]. AB - Reliable determination of bone loss in the skeletal system depends on the accuracy of bone mineral density (BMD) measurements. We investigated short-term and long-term accuracy in vitro and in vivo using a new, commercially available special-purpose computed tomography scanner (Single Energy Peripheral QCT: XCT 900, Stratec FRG) for BMD measurements. Using a phantom, the long-term accuracy (3 months) in vitro yielded a coefficient of variation (cv) of 0.18%. Repeated measurements in 37 patients showed excellent reproducibility, with a cv of 0.71%. The differentiation into groups of low, average and high trabecular bone density demonstrated values of 0.61%, 0.59% and 0.98%, respectively for cv. BMD determination with pQCT is a high-precision method. It seems to be suitable for detection of trabecular bone loss in the range of the annual decrease in bone mass, provided the forearm is positioned with maximum care. PMID- 1598416 TI - [Measurement of the blood flow velocity in the pulmonary arteries using the magnetic resonance technique]. AB - MR blood velocity measurements were performed by the RACE technique in a plane perpendicular to the flow of the pulmonary arteries. MR findings were correlated with those of perfusion scintigraphy, Doppler US and right heart catheter (thermodilution). The ratio of MR blood flow measurements of right and left pulmonary arteries correlated well with the results of perfusion scintigraphy (RPA to LPA) and Doppler. Poor correlation was found when comparing MR blood flow measurements with right heart catheter since absolute flow measurements can be superimposed by neighboring blood vessels in complex anatomic situations. PMID- 1598417 TI - [Intraabdominal calcifications. Lymph node calcifications following mesenterial tuberculosis]. PMID- 1598418 TI - Embryonic olfactory learning in frogs. AB - We examined the effect of embryonic olfactory experiences on behaviour after hatching in two species of anuran amphibians, Rana temporaria and Rana sylvatica. Odorants (orange and citral) injected into the egg were "learned" by the embryo and subsequently preferred by tadpoles after hatching. The observed preferences were specific to the odours experienced prior to hatching, and tadpoles discriminated between the odour experienced as embryos and a novel odour. The acquired preference was maintained after metamorphosis for those individuals that exhibited a preference as tadpoles. Preferences of tadpoles were also influenced "naturally" by odours present in the water surrounding the developing embryos. The experimentally induced olfactory preferences did not appear to influence the exhibition of sibling recognition abilities. The study represents the first demonstration of "embryonic" learning in amphibians, and the functions and importance of early olfactory learning for amphibians are discussed. PMID- 1598419 TI - Modification of prenatal auditory experience alters postnatal auditory preferences of bobwhite quail chicks. AB - This study assessed the effects of altered prenatal auditory experience on bobwhite quail chicks' (Colinus virginianus) species-specific preference for the bobwhite maternal call. Results revealed that when the repetition rate of the embryonic vocalizations normally present in the prenatal environment was altered, the species-typical auditory preference of hatchlings for the maternal call was also altered. Specifically, embryos exposed to embryonic vocalizations with a faster repetition rate than normal subsequently preferred a bobwhite maternal call with a faster repetition rate over one with its normal repetition rate. Bobwhite embryos thus appear able to abstract features of their prenatal auditory environment to other auditory events in the postnatal period. This demonstration of prenatal perceptual learning is in keeping with other recent studies from behavioural embryology, which have also demonstrated that prenatal perceptual experience can influence later responses to species-typical stimulation. PMID- 1598420 TI - Habituation in the rat fetus. AB - Rat fetuses exhibit motor and cardiac responses to chemosensory stimulation on Days 20 and 21 of gestation. The first experiment demonstrated that fetuses exhibit an increase in overall motor activity and decrease in heartrate in response to an initial intraoral infusion of a lemon solution. After a series of nine exposures, however, fetuses no longer exhibit motor or cardiac responses to lemon infusion, suggesting the existence of a habituation-like process. Responsiveness recovers spontaneously following a 3- to 9-min period without stimulation. In a second experiment, a dishabituation treatment was administered to distinguish habituation, which is a centrally mediated decrement in response, from effector fatigue, sensory adaptation, and other peripheral mechanisms that can result in reduced responsiveness. A single infusion of mint following a series of nine lemon exposures was effective in reinstating fetal motor responses to lemon on both Days 20 and 21, but reinstated cardiac responses only on Day 21. Rat fetuses habituate to repeated chemosensory stimulation, suggesting the utility of the habituation paradigm in measuring CNS development during the perinatal period. PMID- 1598421 TI - Fetal behavioural states: sleep and wakefulness? AB - The behaviour of fetuses in utero is often described using terms that were originally devised to describe behaviour after birth. This article considers a definition of the states of coma, sleep, and wakefulness, using criteria that might equally be applied before and after birth. Current knowledge of behaviour of the sheep and human fetus is discussed in the light of such criteria. It is concluded that these species do not appear to be comatose in utero. At present there is insufficient evidence to conclude that sleep and wakefulness exist in utero. PMID- 1598422 TI - Olfaction in utero: can the rodent model be generalized? AB - In this article we discuss five requirements that theoretically must be fulfilled for transnatal chemosensory learning to occur in three placental species, the rat, the sheep, and the human, viz. (1) minimum or partial maturity of nasal chemoreceptor systems, (2) efficient odorivector compounds in the fetal environment, (3) the ability to memorize chemosensory information across birth, (4) perinatal continuity in chemical signals, (5) neonatal ability to detect air borne odorants previously experienced in the aquatic environment. A substantial body of data is reviewed for the rat, in which fetal chemosensation is now firmly established. The less studied ovine perinate also shows preliminary evidence of nasal chemoreception and of postnatal retention of prenatally experienced odorants. Concerning the human species, we discuss extensive anatomical data supporting nasochemoreception in utero, but as yet no direct or indirect functional demonstration is provided. Furthermore, the strongest evidence of odorivector compounds in amniotic fluid is from human data. The results presented allow generalization of chemosensory functioning in utero in the species considered. PMID- 1598423 TI - Decelerative cardiac responsiveness to acoustical stimulation in the near term fetus. AB - Human fetal cardiac responses (36-39 weeks gestational age) to brief, repeated vocal stimuli (male or female voice uttering the same sentence), given at 90-95 dB SPL ex utero (around 20-30 dB less in utero) during a state of low fetal heart rate (FHR) variability, were examined using highly conservative statistical criteria taking into account each subject's prestimulus FHR variability. Subjects exposed to either of the two stimuli displayed significantly more decelerative heart rate (HR) changes compared to control subjects receiving no stimulation. The decelerative changes started during the first seconds following the onset of stimulation and reached their amplitude peak within 10 or 20 sec, depending on the subject. The direction--HR acceleration or deceleration--and the amplitude of the response depended on prestimulus HR variability only, not on prestimulus level. No major difference was found between the effects of the two voices. The data are compared to previous studies demonstrating fetal decelerative changes to acoustic stimuli of less than 105 dB SPL. The choice of an objective criterion to define an HR response and the possible orienting response nature of the decelerative change are discussed. PMID- 1598424 TI - Agricultural pesticide exposure data bases for risk assessment. AB - For pesticide registration, data on toxicity and on occupational exposure are required. In the smaller countries, such as The Netherlands, only a small number of studies on exposure will be available for a proper risk assessment. Therefore, the primary data have to be obtained mainly from the literature. In this review the exposure data available in the formally published literature and from a few Dutch reports for mixing, loading, and application of pesticides are considered for the development of generic/surrogate data bases with which for a specific case (e.g., a new pesticide) the exposure can be estimated for use in a first step of risk assessment. The general aspects of the determination of exposure to pesticides under field conditions are considered, as well as the published proposals for generic data bases. It is concluded that the development of data bases is possible in principle, although in many cases, depending on the type of technique for mixing/loading and application, not enough data are available. Data bases on re-entry have not been proposed in the literature, although many studies on exposure after reentry have been reported. In view of the fact that in some cases the mixer/loader is not the same person as the applicator and considering the different hygienic approach that may be needed for diminishing exposure during these types of work, data on exposure during mixing and loading and on exposure during application were considered separately whenever possible or reasonable. Since data on exposure may vary considerably in daily agricultural practice and since the data sets are in most cases relatively small and not homogeneous, it is impossible to calculate statistically valid means or percentiles. Therefore, estimates have been made which are called indicative values. For risk assessment such estimates, to be used in a first approximation without further specific knowledge on chemical properties of the pesticide, need to be high percentiles, since all 'normal' situations have to be considered and a high degree of worker protection should be achieved. From the data, indicative 90th percentiles of exposure have been estimated and expressed as amount of formulated product per hour of mixing and loading and expressed in amount of spray liquid per hour application. These 90th percentiles are presented in Table 9. As can be seen from Table 9, for various application techniques no data on exposure were available in the open literature, or the number of published data was considered insufficient to obtain indicative surrogate levels that can be used in registration procedures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1598425 TI - [The treatment of arterial hypertension can save 12,600 lives annually]. PMID- 1598426 TI - [A serum immunoglobulin study in patients with tuberculosis and human immunodeficiency virus infection]. AB - We present the immunoglobulin spectrum in a series of 156 HIV-infected patients who were affected of tuberculosis (TB) of different localization. Sixty-seven patients had lung TB, in 13 cases lung TB and an opportunistic infection were diagnosed simultaneously and in 76 cases TB was localized outside the lung. The cases were compared to 62 HIV-infected patients classified in stage 11 (CDC 1986) and to 85 cases of HIV-infected patients who suffered carinii pneumonia (PCP). The most outstanding differences were established between IgA of patients with lung TB and group PCP (p less than 0.001). IgG showed significant differences between lung TB patients and the PCP group (p less than 0.001). PMID- 1598428 TI - [Primary angiosarcoma of the heart. A report of a new case and a review of the literature]. AB - The case is presented of a primitive heart angiosarcoma (PHA) in a 53-year-old woman who developed repeated episodes of hemopericardium with cardiac tamponade. A literature review is performed. PHA is the most frequent primitive cardiac tumor. It is usually localized in the right striatum and is accompanied by effusion of pericardium and right heart failure. The diagnosis is usually made late and bidimensional echography is of great value. Treatment is surgical, if possible. Chemotherapy protocols are being used but with obscure prognosis. PMID- 1598427 TI - [The effects of ticlopidine and nifedipine on platelet aggregation in patients with obliterating arteriopathy of the lower limbs]. AB - This paper evaluates the antiaggregant action of ticlopidine and nifedipine in patients with obliterate arteriopathy in inferior limbs of arteriosclerotic etiology (OAIL). They were established 4 study groups: control, with health volunteers without treatment (N = 10); patients treated with placebo (n = 11); patients treated with 500 mg/day of ticlopidine (n = 12) and treated with 30 mg/day of nifedipine (n = 12). The last 3 groups the treatment duration was 30 days. It was studied the platelet aggregatory activity against ADP and collagen, before drug administration and at 15 and 30 days post-treatment. Our results suggest that: Platelet aggregation is increased in patients with AOMI compared with that observed in the control group. Ticlopidine inhibits platelet aggregation induced by ADP, but not that induced by collagen. Nifedipine doesn't produce any effect on platelet aggregation. PMID- 1598429 TI - [Gammagraphic findings in hepatic focal nodular hyperplasia]. AB - Two cases, of focal nodular hyperplasia (FNH) are presented which were detected by chance and in which the gammagraphic study was the only parameter which indicated the changes that occurred in the hyperplasia revealing a hypervascular mass, colloid capture and 99mTc-DISIDA retention in the later image. These liver masses are now seen more frequently given the wide use of echography and the gammagraphic studies could be useful in the orientation of their nature in a non aggressive manner. PMID- 1598430 TI - [The reactive hemophagocytic syndrome associated with immunoblastic B-cell lymphoma]. AB - The reactive hemophagocytic syndrome is a rare clinical-pathological entity which usually has a benign evolution and which is characterized by the systemic proliferation of mature histiocytes, with a great phagocytosis ability and which occurs in a secondary form in some infections and neoplasias and after the administration of certain drugs. We present a case of reactive hemophagocytic syndrome in a patient presenting a non-Hodgkin lymphoma, of crest malignancy, B immunoblastic and kappa monoclonal, with fatal evolution and in which the diagnosis was obtained after necropsy. PMID- 1598432 TI - [A 60-year-old patient with recurrent angiomatous lesions]. PMID- 1598431 TI - [Cutaneous vasculitis during bacteremia caused by Meningococcus serogroup B]. AB - We report a patient with an upper respiratory tract infection who presented outbreaks of erythematosus-purpuric macules and papules (the pathological substrate of which was a leukocytoclastic vasculitis with numerous intravascular thrombi) coinciding with two autolimited febrile episodes. In serial hemocultures B meningococcus was identified oral antibiotic treatment was given achieving a good clinical evolution. Although both episodes could be considered as a meningococcemia without sepsis, they could also correspond to the initial phase of a chronic meningococcemia. The possible etiopathogenesis of the cutaneous lesions is discussed and the therapeutic and prognostic repercussion of an early identification of these forms of meningococcal disease, which are poorly expressed clinically, are highlighted. PMID- 1598434 TI - [Seropositive rheumatoid arthritis as a paraneoplastic phenomenon in chronic myelomonocytic leukemia in an accelerated phase]. PMID- 1598433 TI - [The relevance of mortality due to circulatory system diseases in Spain]. AB - Cardiovascular diseases is the first cause of death in Spain, as it occurs in most western countries, with a crude death rate of 306 per 100,000 inhabitants in the male population and 351 in the female population in 1987. While this represented a 44.9% of all death causes in 1976, it represented a 42.6% in 1987. Death due to cardiovascular diseases, once corrected for the aging population, has decreased at a yearly rate of 1.26% in males and 1.6% in females from 1968 to 1987 (last year with available date). Most part of the decrease is due to a mean annual decrease of 3% in cerebrovascular mortality since the mid 70s, followed by a reduction in coronary deaths, slightly above 1% annually, since approximately the same time. The changes in life style that have taken place, together with medical and surgical advances and the influence of other factors which have not been so widely studied could be responsible for the potential saving of over 12,000 deaths due to cardiovascular diseases, which would have been added to those occurred in 1987 if mortality rate due to cardiovascular diseases had been the same as in 1976. The difficulty to assign a quantified degree of responsibility changes constitutes a research challenge, not discrediting the preventive action on this facts which are already known. PMID- 1598435 TI - [Partial necrosis of the tongue as the manifestation of giant-cell arteritis]. PMID- 1598436 TI - [Acute kidney failure due to sulfadiazine in the treatment of cerebral toxoplasmosis]. PMID- 1598437 TI - [Multiple symmetrical lipomatosis associated with idiopathic hemochromatosis]. PMID- 1598438 TI - [Latent iron deficiency and esophageal web]. PMID- 1598439 TI - [The diagnostic key in cerebral lymphoma]. PMID- 1598440 TI - [Chemical pleurodesis assessment in compromised patients with a persistent air leak]. PMID- 1598441 TI - [Hypercalcemia as the form of presentation of lymphoma]. PMID- 1598442 TI - [Cardiac tamponade as the first manifestation of a pulmonary neoplasm]. PMID- 1598443 TI - [The Revista Espanola de Anestesiologia y Reanimacion and its foreign image]. PMID- 1598444 TI - [Evaluation of 2 techniques for ventilation support during single-lung ventilation]. AB - In a group of 22 patients undergoing thoracotomy we compared two techniques of ventilatory assistance to the nondependent lung during single lung ventilation. We simultaneously administered a 0.5% FiO2 to the dependent lung. We used a CPAP system with continuous O2 flow limited by an underwater valve at a pressure of +5 cmH2O. We performed 33 ventilatory assistances: in 15 cases to the nondependent lung (CPAP group) and in 18 patients to the lower lobe of the nondependent lung (lobar CPAP group). Evaluation of both techniques was performed by means of arterial blood gas measurement and the mean values were compared using the student's t test. During single lung ventilation the PaO2 in CPAP group increased from 85.86 +/- 22.28 mmHg to 155.52 +/- 59.54 mmHg (p less than 0.001) and in the lobar CPAP series it increased from 88.75 +/- 24.34 mmHg to 122.36 +/- 43.21 mmHg (p less than 0.01). In 11 out of the 22 patients we firstly applied the lobar CPAP and thereafter the CPAP to the whole lung in order to compare the efficacy of both techniques in the same patient. The PaO2 during single lung ventilation was 86.9 +/- 22.7 mmHg and it increased to 111.1 +/- 37.9 mmHg after lobar CPAP (p less than 0.01) ant to 163.3 +/- 64 mmHg after total lung CPAP ventilation (p less than 0.001). Our results confirm the usefulness of both techniques and they indicate that CPAP to the whole nondependent lung is the most effective. PMID- 1598445 TI - [Scheduled autotransfusion in orthopedic surgery]. AB - We report the results of a programmed autotransfusion protocol applied to 22 patients undergoing orthopedic surgery. The number of extractions depended on the surgical needs and on the scheduled time for surgery. Among the total amount of blood used in this study, 81.7% corresponded to the volume previously given by the patient. This volume was sufficient for autologous transfusion in 17 patients. The remaining 18.3% of volume corresponded to homologous blood. We compared the hematologic data obtained at the beginning of the protocol and at the immediate pre and postoperative phase. We found statistical differences among hemoglobin levels, hematocrit, mean corpuscular hemoglobin, and mean corpuscular volume. We conclude that programmed autotransfusion constitutes an ideal method to compensate blood losses during surgery. This method may be the future for hemotransfusion in programmed surgery. PMID- 1598446 TI - [Requirements for uniformity of manuscripts submitted to biomedical journals. International Committee of Medical Journal Editors]. PMID- 1598447 TI - [The laryngeal mask]. PMID- 1598448 TI - [Usefulness of pulse oximetry in thoracic surgery]. AB - Saturation of hemoglobin in arterial blood was simultaneously measured by co oximetry (SaO2) and by pulse oximetry (SpO2) in 228 samples from 42 patients undergoing general anesthesia for thoracic surgery. Data was referred to SaO2 obtained with arterial catheterization. We found a significant correlation (r: 0.949 and p less than 0.001) and the mean differences were 0.77 +/- 1.84. The correlation between PaO2 and the difference among both methods was significantly negative (r: -0.20; p less than 0.001). Although there was a significant correlation, the method loses reliability and accuracy in patients with hypoxemia. In these patients oximetric values are slightly lower than those obtained with arterial cannulation. We emphasize the clinical usefulness of this technique since it is instantaneous and allowed immediate therapeutic actions. PMID- 1598450 TI - [Primary lesions caused by explosions]. AB - The lesions produced by the expansive wave are characteristic of severe injury produced by explosion. This type of injury is being classified as primary lesion. We report a 28 years old male patient who suffered amputation of both lower extremities associated with hypovolemic shock. The patient presented primary tympanic perforation and pneumothorax after initiation of mechanical ventilation at positive pressure. In the discussion section we analyze the physical mechanisms leading to this primary lesion and we indicate the organs most commonly affected. We rise general considerations dealing with the management of these patients and we remark the advantages of a coordinated medical attendance policy. PMID- 1598449 TI - [Acute pulmonary edema secondary to acute upper airway obstruction]. AB - We report a 72 years old woman with mild arterial hypertension and no other pathological history who presented an acute pulmonary edema due to acute obstruction of the upper airway secondary to vocal chord paralysis developing during the immediate postoperative phase of thyroidectomy. The acute pulmonary edema resolved after application of tracheal reintubation, mechanical ventilation controlled with end expiratory positive pressure, diuretics, morphine, and liquid restriction. We discuss the possible etiopathogenic possibilities of this infrequent clinical picture and we suggest that all patients who suffered and acute obstruction of the upper airways require a careful clinical surveillance in order to prevent the development of the pulmonary syndrome. PMID- 1598451 TI - [Intrathecal administration of morphine, midazolam, and their combination in 4 patients with chronic pain]. AB - We have evaluated the analgesic effect of continuous intrathecal administration of midazolam in 4 patients using a three-level score (no change, amelioration, and marked improvement). The secondary effects of this drug were also investigated (sedation, nausea, vomiting, respiratory depression, urinary retention, motor dysfunction). In one patient midazolam was the only drug administered, whereas in three patients this drug was associated with morphine. In one patient with a peripheral arteriopathy, midazolam at a dose of 12 mg/day was unable to equal the analgesic effect achieved with 0.4 mg of morphine. The remaining three patients had carcinoma and received a continuous intrathecal perfusion of morphine at increasing daily doses up to 12; 4,8; and 6 mg/day, respectively without pain relief. In these patients the association of midazolam at respective doses of 9; 4-8; and 6 mg/day induced amelioration in one patient and marked improvement in the two other patients. Midazolam did not change the heart rate, respiratory rate, arterial blood pressure, nor body temperature. We believe that the analgesic effect of intrathecal administration of midazolam is due to its coupling with the ionophore complex GABA-spinal benzodiazepine that in turn produces an increment of the GABA amino butyric acid at this level. PMID- 1598452 TI - [Chylothorax. An infrequent complication in surgical exeresis of the esophagus]. AB - We report a case of massive bilateral chylothorax occurring after surgical resection of the esophagus in a patient with esophageal neoplasm. The surgical approach consisted of a thoracotomy and a cervicostomy. The relevance of this case is based on the low incidence of chylothorax after esophageal surgery. The literature indicates an incidence of about 0.9 to 3%. In our series of 200 patients operated on during the last 10 years we found and incidence of 2%. The patient herein reported presented an immediate postoperative clinical picture of respiratory insufficiency associated with the presence of milky fluid in the pleural drainage. Hematologic and biochemical examination of the pleural fluid confirmed the diagnosis of chylothorax. During the first 24 hours we collected a total volume of 2,500 ml of chyle. The patient was treated with conservative procedures including parenteral nutrition and intravenous reposition of fluids. After 48 hours the total volume of chyle reached 8,500 ml and the patient died. PMID- 1598453 TI - [Intraoperative arrhythmias in a patient with mitral valve prolapse]. AB - We report a case of mitral valve prolapse in which the first manifestation was the occurrence of arrhythmias during anesthesia. A 28 years old female patient, ASA I, without previous medical or surgical history was programmed for surgical repair of an anal fistula. Preoperative physical and laboratory examination were normal. During anesthetic induction with propofol and droperidol and coinciding with orotracheal intubation the patient developed ventricular premature beats, bigeminy, and runs of ventricular tachycardia which were controlled with intravenous lidocaine. Anesthesia was maintained with 66% of O2/N2O, 0.5 to 1% of isoflurane, alfentanil, and atracurium. At the beginning of the intervention the patient presented an episode of supraventricular tachycardia at a rate of 140 to 160 beats/min which did not respond to a deeper anesthetic level nor to the administration of 5 mg of verapamil. This arrhythmia was finally interrupted with 3 mg of propranolol and it did not relapse during the surgical procedure. We discuss the physiopathology of the lesion, the possible arrhythmic effect of the anesthetic agents used in this case, and the effects of several pathologic situations (anemia, pain, anxiety, hypovolemia, etc) documented in patient with this abnormality. PMID- 1598454 TI - [Hemorrhagic shock caused by rupture of the iliac vein. A very rare complication of hip arthroplasty]. AB - We report the case of a 51 years old woman who underwent replacement of a total prosthesis of the right hip under general anesthesia and during left lateral decubitus. During the surgical procedure we observed signs of hemorrhagic shock and a concealed bleeding was suspected. After a diagnostic peritoneal puncture we performed a midlaparotomy which revealed a large retroperitoneal hematoma produced by rupture of the right internal iliac vein. Reanimation of the patient included a massive transfusion of 28 units of blood. We analyze the mechanisms of this rare complication which occurs during total arthroplasty of the hip. We recommended routine monitoring of the central venous pressure in this type of surgery since it is associated with large blood losses. PMID- 1598455 TI - [Medicine, publicity and the press]. PMID- 1598456 TI - [Where are we headed?]. PMID- 1598457 TI - [Delayed respiratory depression after intradural morphine]. PMID- 1598458 TI - [The 1st self-experiments with ether performed by Spanish physicians in the year 1847]. PMID- 1598459 TI - [Arterial hypertension in the adolescent: its possible relation to the salt taste threshold]. AB - The purpose of the study was to define the relationship between the salt intake and the levels of arterial blood pressure in adolescent people. Seventy-eight youngs between 12 and 18 years old with diastolic/systolic blood pressure above 95 percentile formed the hypertensive group; a similar population with the same characteristic (age, sex, race, weight and height) with normal blood pressure were selected as a control group. The salt taste threshold was carried out through tasting a saline solution in different concentrations, till it could be distinguished as salted. Moreover, 45 hypertensive adolescent were follow-up for 12 weeks under a hiposodic diet and consequently a new salt taste threshold was done. The results showed that the control group had a salt perception under 80 mg %, instead the hypertensive group showed a higher threshold (above 160 mg %). Those hypertensive adolescent which were followed for 12 weeks changed its pattern in this way: in 24, a lesser perception was observed with a reduction in their blood pressure in 11 of them. These findings suggest that hypertensive adolescent had an elevated threshold for salt, usually above 160 mg % and the test should be helpful for the identification of a subgroup "salt-sensible". PMID- 1598460 TI - [An analysis of the circadian rhythm of the heart rate and arrhythmias in healthy elderly subjects]. AB - The incidence of asymptomatic arrhythmia detected by Holter monitor in the normal aged population is high. Nevertheless, there are few studies in the literature about the existence and characteristics of their circadian rhythm (CR). The aim of this study, is to determine the presence of CR of the heart rate (HR), supraventricular and ventricular extrasystoles (SVE, VE), atrial tachycardias (AT) and ventricular complex tachycardias (VCT) in the normal aged population. We studied 120 subjects, older than 70 years of age, belonging to a pensioner club, without apparent cardiovascular disease by history, physical, ECG, Chest X-Ray and echocardiography. All the patients had a 24 hours Holter monitor. 42 patients whose recording showed more than 50 SVE and/or more than 50 VE were included in the study. To study the CR the cosinor method was used. In the simple analysis, the HR had significant CR in 40 subjects (95.2%), the SVE in 18 out of 29 (62.1%) and the VE in 16 out of 26 (61.5%). The global analysis showed significant CR for the HR, with an acrophase at 15:47 hours (confidence limits at 95% between 14:45 and 15:42 hours) and for the VE, (acrophase: 15:35 hours, confidence limits between 11:53 and 19:05 hours). There was not significant CR for the SVE because the wide dispersion of the acrophases between the subjects. The AT had significant CR but no the VCT. We conclude that the majority of the aged normal subjects with frequent ectopy had significant CR for the HR and extrasystoles. The VE follow a CR similar to the frequency, suggesting a common modulation of the autonomic nervous system. The SVE variation follow a different CR. PMID- 1598461 TI - [Prognostic predictors of left ventricular aneurysm after myocardial infarct]. AB - We have prospectively studied the prevalence and natural history of left ventricular aneurysm in a series of 386 consecutive male patients with an acute myocardial infarction. Definition of aneurysm was angiographic and based on a single plane left ventricular angiogram. There were 52 (13.5%) left ventricular aneurysms. Mean follow-up was 57 +/- 29 months (range 40-100). During this interval, 15 of the 52 patients died (29%). Univariate analysis showed that survivors had at admission significantly less prevalence of hypercholesterolemia, previous myocardial infarction and intraventricular conduction disturbances. In addition, their Killip class was better (p less than 0.02) and the left ventricular ejection fraction was higher (p less than 0.002). The survival rates of patients with ventricular aneurysm at 1, 3 and 5 years were 88, 82 and 75%, respectively. Left ventricular end diastolic pressure, number of diseased vessels and the presence of bifascicular block were independent predictors of survival. Stratification of patients according to the risk factors allowed identification of patients with excellent prognosis (those with left ventricular end diastolic pressure less than 20 mmHg, single vessel disease and no conduction disturbances) and others with high risk of death (left ventricular end diastolic pressure greater than or equal to 20 mmHg, three vessel disease and bifascicular block). Survival at 5 years for these two groups were 81% vs 50%, respectively (p less than 0.005). PMID- 1598462 TI - [The correlation between measurements performed by intravascular echography and quantitative digital angiography in large- and small-caliber arteries]. AB - Intravascular ultrasound is a new promising technique that appears as a very useful complement to standard angiography in the study of atherosclerosis. Specifically, intravascular ultrasound provides by itself, information of great value concerning vessel wall characteristics. Nevertheless, before taking any decision with the results provided by this new technique, we must validate this information with that provided by other more conventional techniques like standard angiography. Accordingly, we have analyzed in 25 patients, 50 images of the abdominal aorta and 77 images of the coronary arteries taken from arterial segments free of atherosclerotic involvement. With the use of a calibrated small grid located over the patient's thorax, we have analyzed "in the same points" the images obtained with intravascular ultrasound and those provided by contrast angiography using a quantitative angiographic analysis. In the abdominal aorta the vessel diameter measured by intravascular ultrasound and angiography was 17.8 +/- 0.39 mm vs 18.6 +/- 0.42 mm (NS), whereas in the coronary arteries it was 2.76 +/- 0.39 mm vs 2.98 +/- 0.37 mm (NS), respectively. The correlation between both techniques was good for both types of arteries (r = 0.93 in the abdominal aorta and r = 0.87 in the coronary arteries). We conclude, that in our experience and with the methodology used, there is a good correlation between the measurements of the vessel diameters obtained by both intravascular ultrasound and digital angiography in arteries of different sizes, being the correlation even better in large arteries. PMID- 1598463 TI - [The perioperative management of aortic coarctation in the neonatal period]. AB - Clinical records of 30 neonates with aortic coarctation admitted to neonate ICU from January 1985 to June 1990 are reviewed. We analyzed perioperative data to search for adverse prognostic signs. Patients weights were 2,970 +/- 500 grams and gestational age 38.5 +/- 1.7 weeks. Mean age at admission was 10.5 +/- 10 and mean age of surgery 13 +/- 11 days. 70% had associated congenital heart defects. Surgical technique was patch angioplasty in 86% and subclavian flap in 14%. Early or late mortality among patients with isolated aortic coarctation was nonexistent, and it was 28.5% in patients with other congenital heart defects. 13% has postoperative hypertension and 3.3% recoarctation. Adverse prognosis signs were preoperative (associated congenital heart defects, especially ventricular septal defect and interrupted aortic arch, greater dose of catecholamines and mechanical ventilation), intraoperative (pulmonary artery banding), and postoperative (hypotension, cardiac failure, arrhythmia, oligoanuria, metabolic acidosis, greater need of mechanical ventilation, bleeding and thrombopenia). Date are compared with other neonatal series. PMID- 1598464 TI - [The effect of low-dose acetylsalicylic acid on platelet aggregation parameters in vitro]. AB - In order to elucidate whether a single dose of 150 mg acetylsalicylic acid three times a day, provokes significant changes into platelet aggregation, we analyzed a group of 50 patients who underwent coronary revascularization. During 48 hours before surgery, all patients received 100 mg dipyridamole orally every 6 hours and 1 hour after the end of the operation 100 mg dipyridamole via nasogastric tube. Patients were then randomized into three groups to receive 3 times a day a capsule containing: 50 mg acetylsalicylic acid, 50 mg acetylsalicylic acid plus 75 mg dipyridamole or placebo. Before the antiplatelet therapy was started, the day of the operation and 5 days after the onset of the treatment, blood samples were taken to determine platelet aggregation (turbidimetric technique) and the thromboxane A2 liberation. The three groups were comparable for all the studied clinical and angiographic variables. Preoperative dipyridamole did not provoke significant changes in platelet aggregation (acetylsalicylic acid group 86.5 +/- 10% vs 71 +/- 28.8%; acetylsalicylic acid + dipyridamole group 81.5 +/- 7.8% vs 75.3 +/- 22.7%; placebo group 83.7 +/- 8.9% vs 70 +/- 21.5%). After 5 days of treatment with acetylsalicylic acid, both groups under active treatment showed a significant (p less than 0.001) decrease of aggregability (acetylsalicylic acid 12.8 +/- 4.4%; acetylsalicylic acid + dipyridamole 20.5 +/- 17%; placebo 72 +/- 21.5%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598465 TI - [Chronic heart failure (VIII). The present and future of the heart transplant in the treatment of chronic heart failure. The role of mechanical circulatory assistance]. PMID- 1598466 TI - [Changes in the flow patterns of the hepatic veins obtained by pulsed Doppler during the postoperative follow-up of a patient with acute aortic insufficiency]. AB - Blood flow pattern recording of hepatic veins using pulsed Doppler technique is a valid method for the assessment of hemodynamic changes in right atrium. We describe a patient with severe aortic regurgitation secondary to acute infective endocarditis who underwent surgical repair. Before surgery and during the postoperative period, several evolutive studies (including conventional echo and hepatic veins pulsed Doppler recordings) were performed. The different central blood flow patterns were correlated with changing hemodynamic conditions during follow-up of the patient. These central flow velocities reflect changes in right atrial pressure contours, and are easily obtained non-invasively with pulsed wave Doppler ultrasound of the hepatic veins. They could be an useful method for assessing right heart filling dynamics, reporting characteristic patterns in other cardiac disease states. PMID- 1598468 TI - [The independent origins of the anterior descending, circumflex and right coronary arteries from the right coronary sinus]. AB - We present a patient with chronic ischaemic cardiac disease and anomalous left anterior descending and circumflex coronary arteries with independent origin from the right Valsalva sinus. Each one had his own ostium and the left anterior descending artery followed an intramyocardial pathway through the interventricular septum whereas the circumflex artery had a retrocardiac pathway. The clinical picture of the patient was related to the presence of atherosclerotic obstructive lesions in right, whose origin and curse were normal, and circumflex coronary arteries. He was treated medically at first but without obtaining complete control therefore he needed surgical treatment which was undertaken without technical difficulties. We reviewed the anomalies of the main coronary arteries, in the origin and course, with its clinical signification, diagnosis and therapeutics topics. PMID- 1598467 TI - [Acute posttraumatic myocardial infarct: the necessity of an early interventionist posture]. AB - We describe five cases of posttraumatic anterior acute myocardial infarction in young patients, without previous heart disease. One case was treated with intracoronary thrombolysis and angioplasty, 3 cases received systemic thrombolysis, and the last one did not have any re-permeabilization therapy, having arrived to the hospital 72 hours after the episode. The coronary angiograms showed at the left anterior descending artery: thrombosis in 3 cases, coronary dissection in one case, and slow flow with no morphological lesions in the other. The case which not received thrombolytic therapy developed a severe left ventricular dysfunction. In conclusion we emphasize an early angiographic study, in order to decide the re-permeabilization therapy. PMID- 1598469 TI - [A free-ball thrombus in the left atrium in the absence of mitral pathology]. AB - One male 53-year-old that was diagnosed of dilated myocardiopathy two years ago, was admitted at the emergency room by acute pulmonary oedema, showing the two dimensional echocardiographic study one free-floating thrombus in the left atrium. Waiting for surgery the patient suffered a syncope that was diagnosed of embolic origin and the left atrial thrombus has disappeared. PMID- 1598470 TI - [A house for autistic children]. PMID- 1598472 TI - [Too much, three times too much. Interview by Odile Burrus]. PMID- 1598473 TI - [The nurses too]. PMID- 1598471 TI - [Private duty nurses: that that will change]. PMID- 1598474 TI - [Order in disorder]. PMID- 1598475 TI - [AIDS, the latest numbers]. PMID- 1598476 TI - [Surveillance of HIV]. PMID- 1598477 TI - [Ten years of geriatric assessment]. PMID- 1598478 TI - [Thoracic endoscopy as seen by the nurses]. PMID- 1598479 TI - [Indemnification law for hemophiliacs and transfused patients]. PMID- 1598480 TI - [Cancer of the thyroid]. PMID- 1598481 TI - [European education of life support care nurses in intensive care]. PMID- 1598482 TI - [The electroencephalogram (EEG)]. PMID- 1598483 TI - [A slow advance at Lons-Le-Saunier. Interview by Claire Manicot]. PMID- 1598484 TI - [Emergency, students in distress]. PMID- 1598485 TI - [Don't forget the essentials]. PMID- 1598487 TI - [History without words]. PMID- 1598486 TI - [Finding the time and availability to communicate]. PMID- 1598489 TI - [The life of Emma]. PMID- 1598488 TI - [Communication and admission in long term care]. PMID- 1598490 TI - [An inhabited body]. PMID- 1598491 TI - [Recognition passes for audacity]. PMID- 1598492 TI - [Blood products]. PMID- 1598493 TI - [SOS care in the desocialized homeless persons]. PMID- 1598494 TI - [The hiring interview]. PMID- 1598495 TI - The influence of synovial fibroblasts on the phagocytosis of Staphylococcus by polymorphonuclear cells. AB - It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanism that contribute to the increased susceptibility of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surface on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMN may lead to reduced clearance of bacteria from the joint. PMID- 1598496 TI - Production of interleukin 8 by cultured synovial cells in response to interleukin 1 and tumor necrosis factor. AB - Both interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) stimulated the production of interleukin 8 (IL-8) by synovial cells in time and dose dependent manners. Enhanced chemotactic activity of polymorphonuclear cells (PMN) in culture supernatants of synovial cells was neutralized with anti-IL-8 antibody, thus showing synovial cells to be capable of secreting IL-8 which may contribute to PMN accumulation in rheumatoid inflamed joints. PMID- 1598497 TI - Synovial, articular cartilage and bone changes in rapidly destructive arthropathy (osteoarthritis) of the hip. AB - We studied ten femoral heads from eight patients suffering from rapidly destructive arthropathy (RDA) of the hip. At surgery, 1-3.5 ml of synovial fluid, ranging from citrous to hemorrhagic, was aspirated from six joints. This fluid was viscous, pauci-cellular and did not contain calcium pyrophosphate dihydrate (CaPPD) crystals, although significant amounts of alizarin S-positive material was found in three joints. Significant synovial hyperplasia was found in four joints and moderate hyperplasia in two. Synovium was hypertrophic, hypercellular and slightly to moderately fibrotic. It lacked evidence of perivascular inflammatory infiltrates. Synovium often contained amyloid micro-deposits and alizarin S-positive osteocartilagenous debris surrounded by macrophages. Synovial hyperplasia had a good correlation with osteocartilagenous debris and a poor correlation with amyloid infiltration. Femoral heads were usually flattened and exhibited large areas of exposed bone spotted by plugs of fibro-cartilagenous tissue. Subchondral bone contained large ischemic and necrotic areas, bone marrow atrophy and fibrosis, and intense bone remodeling. Subchondral bone necrosis and ischemia were the most significant findings of this study and their role in the development of RDA is discussed. PMID- 1598499 TI - Prevalence of radiographic osteoarthritis in two elderly European populations. AB - Was compared the prevalence of radiographic osteoarthritis (ROA) in two elderly populations, one in Goteborg (Sweden) and one in Zoetermeer (The Netherlands). The comparison was preceded by an inter-observed analysis of 150 films, revealing lower percentage agreements and kappa values when analysing the films on a five point scale compared to the analysis in a dichotomy of "abnormal" and "normal" films. An intra-observer analysis of 50 films revealed higher percentage agreement and kappa values of well over 0.75, suggesting that radiographs could be read by one observer when different populations are being compared. The prevalence of hand ROA was higher in the Goteborg population, while the prevalence of knee ROA showed no significant differences. No significant increase with age of the cohorts was found for hand ROA in either population and no increase with age for knee ROA was found in the Swedish population. In the Zoetermeer population, knee ROA increased with age in both sexes. PMID- 1598498 TI - A human monoclonal IgA rheumatoid factor using the VkIV light chain gene. AB - A human hybridoma stably secreting IgA rheumatoid factor (RF) was produced by cell hybridization with peripheral blood lymphocytes of a patient with rheumatoid arthritis. The RF was of the IgA1 isotype with kappa-light chains and was useful for standardization or specificity controls in class-specific RF assays. RF activity was detected only when the IgA molecular were in a polymeric state, and could be measured by enzyme linked immunosorbent assay as well as in conventional agglutination based tests. The RF had the modified Ga fine specificity described previously for several RFs and for protein A. The immunoglobulin V genes used were isolated and sequenced. The light chain was encoded by the VkIV gene rearranged to Jk2; compared to the published VkIV germ line gene there was 90% nucleotide homology. The heavy chain gene used belonged to the VHI family and was rearranged to JH4. Comparisons with published sequences revealed 90% homology with the recently characterized VH gene expressed by RF-TS3, a rheumatoid synovia RF hybridoma. PMID- 1598501 TI - Malaria and pregnancy in Cameroonian women. Effect of pregnancy on Plasmodium falciparum parasitemia and the response to chloroquine. AB - The interaction between malaria and pregnancy was investigated in an epidemiologic study conducted in Mfou, a rural community in Cameroon. The study consisted of both cross-sectional and longitudinal analyses involving 225 pregnant women and 75 nonpregnant controls. Information was obtained by a standardized questionnaire to determine the pattern of antimalarial drug use. The parasitologic response to chloroquine was also determined. A dosage of chloroquine base (25 mg/kg of body weight) was given to women over a 3-day period, followed by 5 mg/kg doses administered weekly for 4 weeks. The results showed that Plasmodium falciparum infections occurred more frequently in pregnant (45%) than in nonpregnant (31%) women in terms of parasite rates (p = 0.03) and density (p less than 0.003), especially in primigravidae as compared with multigravidae matched for parity and age. Levels of parasitemia were also higher in the second trimester than in the first trimester of pregnancy (p less than 0.01). Failure to clear parasitemia after a chloroquine regimen was more frequent in pregnant than in nonpregnant women (p less than 0.01), particularly in primigravidae. Higher parasitemia and a lower parasitologic response to chloroquine in pregnant women, especially in primigravidae, suggest a relatively low level of clinical immunity and emphasize the need to target this group of women for malaria control strategies. PMID- 1598502 TI - Experiments on cryopreservation of Plasmodium falciparum. AB - A comparative study was carried out in order to assess the effectivity of the deep-freezing conditions for P. falciparum cultures: 1. by plunging them into liquid nitrogen, 2. by use of an established freezing program for lymphocytes. After thawing in a waterbath at 37 degrees C, samples were diluted with equal volumes of 3.5% sodium chloride solution or 15% phosphate-buffered saline supplemented glucose solution. Other samples were not diluted after thawing, but the medium was replaced twice during the first day in culture. Survival was evaluated by counting the parasites in Giemsa-stained smears taken on day 3 after thawing. We obtained the best survival rate using NaCl solution, whereas replacing the medium twice resulted in the lowest level of survival. In synchronized cultures we studied survival rates of the different developmental stages of the intraerythrocytic parasites: young trophozoites (ring stages) and schizonts. The results indicate that irrespective of the freezing technique used, the survival level of young trophozoites was high (40 and 60%). The more sensitive stages (late trophozoites and schizonts) were better protected by using the freezing program designed for lymphocytes. PMID- 1598500 TI - A prospective analysis of liver biopsies in rheumatoid arthritis patients receiving long term methotrexate therapy. AB - Baseline and sequential liver biopsies were performed in ten patients with rheumatoid arthritis (RA) treated with methotrexate (MTX) for more than 4 years. Liver biopsies were performed in all patients before the initiation of MTX therapy and were repeated after reaching a cumulative dose of 1500 mg or more. In four patients a third biopsy was performed 3 years after the first one. No significant worsening of hepatic architecture was found in any of our patients after 4 to 7 1/2 years of MTX therapy. No correlations between histologic findings and various clinical or pharmacological variables could be found. Our results suggested that prolonged MTX administration in RA patients did not cause severe hepatic abnormalities. PMID- 1598503 TI - The effects of ascorbate-induced free radicals on Plasmodium falciparum. AB - Ascorbic acid has been shown to cause stage-dependent effects on the in vitro development of Plasmodium falciparum. While vitamin C marginally enhanced the development of young parasites, it proved highly destructive to the advanced forms. The present study evaluates the mechanisms by which vitamin C affects the parasite. The treatment of parasitized erythrocytes with ascorbate resulted in the conversion of added salicylate to dihydroxybenzoate products, indicating the involvement of hydroxyl radicals. There was a stage specific sensitivity, increasing conversion with progressing parasite development. This specificity could not be attributed to the altered uptake of salicylate by the parasitized erythrocyte, since salicylate uptake was similar in either parasitized or non parasitized erythrocytes. In distinction, increased uptake of ascorbate by parasitized erythrocytes could account for an elevated oxidant stress. The treatment with ascorbate also caused the oxidation of hemoglobin to methemoglobin and the peroxidation of membrane lipids. Added catalase markedly inhibited the ascorbate-induced effects on parasite development. "Free" plasmodia were also vulnerable to treatment with ascorbate like the parasites within their host cells. These results are in accord with a free radical mechanism of damage to the infected erythrocytes. During the growth of P. falciparum the infected erythrocytes release increasing levels of iron-containing structures that are redox-active and can catalyze the formation of highly reactive oxygen derived species. The findings also indicate the multiplicity of the mode of action of ascorbate on the host-parasite system. PMID- 1598504 TI - The activity of platinum, iridium and rhodium drug complexes against Leishmania donovani. AB - The activities of twenty seven Platinum, Rhodium and Iridium drug complexes were determined against Leishmania donovani amastigotes in mouse peritoneal macrophages in vitro. Eight compounds showed antileishmanial activity of which only three, Rh(III)-mepacrine, Ir(III) pyrrolidine dithiocarbamate and Ir(III) diethyl dithiocarbamate had ED50 values of less than 1 microM. The two Iridium complexes produced, respectively, a 50% and 39% suppression of L. donovani amastigotes in the liver of BALB/c mice following the subcutaneous administration of 200 mg/kg for 5 consecutive days. Ultrastructural studies suggest that the amastigote kinetoplast-mitochondrion complex is the primary site of action of the Ir and Rh complexes. PMID- 1598505 TI - Evaluation of Procyclic Agglutination Trypanosomiasis Test (PATT) for the immunodiagnosis of Trypanosoma brucei rhodesiense sleeping sickness in Kenya. AB - Documented sera from 156 patients admitted to Alupe Sleeping Sickness Hospital in Western Kenya were tested to determine the potential usefulness of Procclic Agglutination Trypanosomiasis Test (PATT) for the diagnosis of Trypanosoma brucei rhodesiense African sleeping sickness. A total of 490 serum samples were tested, including 42 controls. Anti-trypanosome antibodies were detected in 99% of the sera taken prior to trypanocidal drug therapy. Antibody levels remained high during course of treatment. In cured cases antibodies declined to negative or low levels 4 months to one year after treatment. High antibody levels persisted in patients who relapsed. Although the results showed a high sensitivity and specificity, confirming the potential usefulness of the test for serodiagnosis of African sleeping sickness, PATT, in its present form is unsuitable for routine diagnosis. This is due to difficulties inherent in the use of live trypanosomes as detector antigen. PMID- 1598506 TI - The residual effect of deltamethrin Spot On when tested against Glossina palpalis gambiensis under fly chamber conditions. AB - Groups of single zebu cattle were exposed to infestations of the tsetse fly Glossina palpalis gambiensis in fly chambers following treatment with a pour on formulation of deltamethrin, Coopers* Spot On. During the experiment one animal was maintained in a stall, the other exposed at intervals to sunlight. Both mortality and knockdown of exposed flies was demonstrated. Mortality rates of greater than 90% were recorded during the period 0-20 days after treatment and values in excess of 50% during the period, 41-59 days after treatment. Knockdown was more marked with rates in excess of 90% and 65% being recorded for respectively 45 and 75 days after treatment. Exposure to sunlight did not significantly effect the performance of Spot On. Flies were observed to repeatedly land on the deltamethrin treated cattle, so contributing to the overall pick-up of effective concentrations of the chemical. It was considered that this effect of the chemical could considerably reduce the risk of transmission of trypanosomosis from the start of a tsetse campaign. PMID- 1598507 TI - Simultaneous control of ticks and tsetse flies in Satiri, Burkina Faso, by the use of flumethrin pour on for cattle. AB - Treatments of 2000 cattle at monthly intervals with flumethrin pour on (1 mg active ingredient/kg b.w.) resulted in a rapid decrease of African Animal Trypanosomosis (AAT). After an initial curative treatment of the sentinel herd with diminazene aceturate (7 mg/kg b.w.) only positive cases were treated. Three applications of flumethrin were sufficient to reduce the prevalence of AAT to below 5%. Apart from a slight increase at the end of the first year the infection rate varied between 0 and 5%. A tsetse population disappeared from a heavily infested habitat after six treatments. The average tick infestation was 3-10 times lower than in a control site inspite of the repeated use of another acaricide. Between 3282 and 8624 animals were treated five times in the second year at intervals of about two months. 130 monoconical insecticide impregnated traps were deployed in habitats which were inaccessible for the cattle. The highest infection rate of the sentinel herd was 1.4%. Among another 150 eartagged cattle scattered over a district of about 1000 m2 the prevalence of AAT dropped to 4.8% at the end of the second year. Emphasis is put on an active and financial participation of the rural communities to ensure a viable campaign and good prospects of a taking over by local organizations once the external interventions have stopped. PMID- 1598508 TI - Analysis of antibody responses directed against two Onchocerca volvulus antigens defined by monoclonal antibodies. AB - Monoclonal antibodies, reactive with antigens solubilised from the body wall of intact female Onchocerca volvulus using 2% 2-beta-mercaptoethanol, have been characterised. Two IgG1 antibodies, Cam1 and Cam28, recognised antigens of apparent molecular weights of 18,000 and 28,000; and 120,000, respectively. The target antigens of Cam1 and Cam28 could be localised in the cuticle. Inhibition ELISAs showed that target epitopes of both monoclonal antibodies induce an antibody response in onchocerciasis patients. 153 sera from Sierra Leonean patients were tested for their individual antibody levels against antigen epitopes recognised by Cam1 and Cam28. Patients within the age of 5-8 years had the highest levels of antibodies against the Cam28-epitope, whereas patients above 60 years had almost none. Amicrofilaremic patients had higher anti-Cam28 antibody levels than microfilaremic patients and there was a significant difference between groups with no chronic skin disease and those with mild or severe signs. A high percentage of patients (80.4%) recognised the Cam1-epitope, highest antibody levels being found in patients within the age group of 15 to 45 years and in microfilaremic patients. However, levels of antibodies inhibiting monoclonal antibody Cam1 could not be correlated with presence or absence of skin disease. PMID- 1598509 TI - Immunological studies on onchocerciasis in Sierra Leone. 2. Cell-mediated immune responses after repeated treatment with ivermectin. AB - Cell mediated responses of peripheral blood lymphocytes were tested by incorporation of I-125 dideoxyuridine in a standard proliferation assay. The cells were collected from age and sex-matched patients selected on the basis of their clinical and parasitological status. These patients were treated with either ivermectin or placebo at 6-monthly intervals for two years. For the purpose of comparison, the patients were divided into three groups: children aged 5-9 years; 10-19 year olds; and, those older than 20 years. Repeated drug treatment over the two year period had no effect on either mitogenic or non parasite antigen (PPD) responses in a majority of individuals. However, in younger children (5-9 years) repeated treatment with ivermectin resulted in some enhancement of Onchocerca-specific responses measured 6 months after administration of the drug. This effect was more pronounced in children presenting with positive skin-snips. An age related decline in mitogenic responses was observed. PMID- 1598510 TI - Field evaluation of IgG4 serology for the diagnosis of onchocerciasis in children. AB - IgG4 serology was evaluated for early diagnosis of onchocerciasis in children living within an endemic focus of forest-type onchocerciasis in Nigeria. IgG4 serology proved to be more sensitive than conventional skin snip examination being able to detect 42% of infected children as opposed to 24% by snip examination. Furthermore, age was not a limitation to the technique within the 8 12 y spectrum. We conclude that IgG4 serology in children is a reliable indicator of community microfilarial rate and ongoing transmission of onchocerciasis. PMID- 1598511 TI - The incidence of pulmonary manifestations during Plasmodium falciparum malaria in non immune subjects. AB - The incidence of clinical pulmonary manifestations during clinically mild Plasmodium falciparum malaria was studied in 50 patients. In nine patients (18%), respiratory symptoms developed and consisted of cough either productive (in 5) or dry and pleuritic (in 3), wheezing and dyspnea (in 2). Physical examination of these patients disclosed minimal decrease of breath sounds with diffuse moist rales over both lung bases. Chest X-rays showed small infiltrates and increased vascular markenings in most. Peak expiratory flow rates were measured in 38 of these patients and showed a mean decrease of 16.9% which reached its nadir on the third to fourth day of disease with return to normal values within 7.7 days. In patients with pulmonary symptoms a marked decrease in PEFR was observed (28.9%) and return to normal values was also longer (9.6 days). We conclude that mild, easily detectable and asymptomatic alterations of pulmonary function are observed in most patients with P. falciparum malaria and the incidence of respiratory manifestations in the uncomplicated forms of the disease is relatively high. PMID- 1598512 TI - The vectorial efficiency of Simulium yahense populations in south-eastern Ghana. AB - Adult female Simulium yahense were identified amongst catches of S. damnosum s. 1. caught at Tsatsadu Falls and Wegbe in south-eastern Ghana. Dissections of stained flies to assess the species' role as a vector of onchocerciasis in the region revealed as many as 357 L3 per 1000 biting flies in a sample from Wegbe. When the data from the two sites were combined 154 L3 per 1000 biting flies and 315 L3 per 1000 parous flies were recorded. The values for wet season samples were about 12% higher than those for the dry season. The results are discussed in relation to other studies of S. yahense populations and regarding the species' recent spread in Ghana and Togo. PMID- 1598513 TI - Effect of ivermectin on experimental gnathostomiasis in rabbits. AB - The efficacy of ivermectin against advanced third stage larvae of Gnathostoma spinigerum was investigated in rabbits. Six experimentally infected rabbits were treated at a single dose, 0.2 mg/kg of ivermectin subcutaneously, four weeks after infection. Another two rabbits were treated, once and three times, with 2 mg/kg at varying numbers of days after infection. Five rabbits served as untreated controls. All rabbits were sacrificed about the 28th week after infection. The reductions of worm load in the treated groups were 74.2% and 84.2% respectively. The immune response, detected by ELISA, was similar in treated and control rabbits. PMID- 1598514 TI - The effect of splenectomy on immunity to Plasmodium malariae and P. falciparum in a malaria immune donor. AB - A 55 year old Liberian male was splenectomized after an abdominal trauma. A few days after splenectomy he experienced a pure Plasmodium malariae infection with high fever. He was later followed for 12 months with monthly blood films and temperature measurements, and did never show any signs of clinical malaria. The parasite densities observed during the longitudinal follow after splenectomy did not differ from parasite densities in villagers with intact spleens. PMID- 1598515 TI - Differential sensitivity of the pre-erythrocytic stages of Plasmodium cynomolgi B to the prophylactic action of primaquine. AB - The sensitivity of the developing pre-erythrocytic stages of Plasmodium cynomolgi bastianelli to primaquine in single, two or three dose regimens administered at varying times during the incubation period has been investigated. The study reveals that the early pre-erythrocytic stages of the parasite are more susceptible to primaquine than the later stages. Regimens of 5.34 mg/kg x 1 dose on day 0 or day + 1; 2.67 mg/kg x 2 doses on days 0 and 1 and 1.78 mg/kg x 3 doses on days -1, 0, + 1 or days + 1, + 2, + 3 protected all the treated monkeys while identical regimens administered after day 3 of sporozoite inoculation were not curative. PMID- 1598516 TI - Distribution of Simulium yahense after larviciding activities in the southern extension of the Onchocerciasis Control Programme. AB - The distribution range of Simulium yahense in the Eastern Operational Area of the Onchocerciasis Control Programme increased after larviciding treatments were started in 1988, to control important Simulium damnosum s. 1. vectors of onchocerciasis. A distribution map indicating the extended range is drawn and the importance of this expansion of S. yahense to disease transmission discussed. PMID- 1598517 TI - An inexpensive and simple method for screening potential antimalarial drugs. AB - The visual in vitro test proved to be a very useful tool for screening a series of 54 chemical analogues for their antimalarial activity. The test relies on the formation of dark pigment precipitates after an alkaline solution is added to synchronous cultures of Plasmodium falciparum. Pigment is produced when a chemical compound is unable to prevent the maturation of rings to schizonts during incubation. However, in the presence of effective concentrations of a compound, maturation is inhibited and, consequently, pigment and precipitation are not observed. By using this procedure, 36 of the inactive or less active compounds could be excluded from assessment by the radioisotopic hypoxanthine incorporation test. This resulted in a substantial reduction in the overall cost of screening these compounds. PMID- 1598518 TI - [Appendicitis]. PMID- 1598519 TI - [What is appendicitis? Anatomopathological notions]. AB - Appendices removed for acute abdominal syndrome have various pathological aspects. In most cases one finds acute inflammatory lesions with a varying degree of penetration into the appendicular wall, but chronic lesions or a quasi normality which do not explain the symptoms are sometimes observed. Peculiar findings, such as parasites, recognizable infective agents or even tumoral proliferations detected by the inflammatory syndrome can be discovered. PMID- 1598520 TI - [Quantified symptomatology of acute appendicitis in adults. The signs and their value]. AB - Using a data base of 7,000 acute abdominal pains, we here described the assessed clinical manifestations of the main diseases responsible for right lower quadrant pain. However, percentages of sensibilities have been replaced by adverbs or adjectives, applying a scale of equivalence. The possible modifications of the positive predictive values have been also replaced by verbs or typical expressions. We first described the acute appendicitis syndrome (which covered congestive endoappendicitis and suppurated appendicitis) with the clinical shades or the gathered and gangrenous forms or even of the diffuse peritonitis. Features of the acute appendicitis contrast with those of the so called "non specified abdominal pains" (a new entity), and those of the subacute or chronic appendicitis. We found a good correlation between clinical and pathological findings. One of the difficulties has been to determine if a subgroup of subacute appendicitis should be or not included into the acute appendicitis. PMID- 1598521 TI - [Appendicitis. Computer-assisted diagnosis. A clinical complementary test]. AB - A computer aid diagnosis of acute abdominal pain has been constructed on a 7,000 cases data base, using a Bayesian model. The system is used as a paraclinic test, increasing the reliability of the physician's clinical diagnosis or questioning that diagnosis in case of discrepancy. PMID- 1598522 TI - [Questionable appendectomies]. AB - Each year in France, 75,000 appendectomies are carried out for normal or fibrous appendix and another 75,000 for a mere inflammation of the mucosa of submucosa. To decrease the incidence--four times higher than in other countries--it is suggested to keep under observation the patient with RIQ tenderness if they have neither rebound nor guarding, a temperature below or equal to 38 degrees C and a white blood cell count lower than 10,000/mm3. By following these guidelines, there is no risk to miss perforated or suppurated appendicitis. PMID- 1598523 TI - [Appendicular peritonitis]. AB - Peritonitis (i.e. acute inflammation of the peritoneum) from appendicular origin, can be due to acute appendicitis or be observed after appendicectomy. Diagnosis is based on physical examination. Imaging procedures (ultrasound and computed tomography) are particularly useful in localized and postoperative peritonitis. Management includes surgery, antibiotics and intensive care. Early surgical treatment by appendicectomy represents the best way to improve the prognosis of the disease. Mortality is mainly observed in case of delayed diagnosis and in aged patients. PMID- 1598524 TI - [Appendicitis in children]. AB - In 1992, appendicitis is still common among children. Mortality due to a belated or erroneous diagnosis is far from being nil. The disease must always be present in the clinician's mind, and its diagnosis is purely clinical. No significant advance has been made on this subject, and clinical findings remain of paramount importance. Hospitalization for observation at the slightest doubt and emergency surgery when the diagnosis is probable are the best means of improving the management of appendicitis in children. PMID- 1598525 TI - [Is a calorie still worth a calorie? From the thermodynamic dogma to practical reality]. PMID- 1598526 TI - [Hysterectomy: an obsolete operation?]. PMID- 1598527 TI - [Fluorine salts and vertebral osteoporosis. Reexamination of a controversy]. PMID- 1598528 TI - [Normal pressure hydrocephalus. The state of the concept in 1991]. PMID- 1598529 TI - [Portable or implantable pancreas. Certain progress for a still far-off practical application]. PMID- 1598530 TI - [Caustic stenoses of the esophagus]. AB - Oesophageal stenosis is a frequent complication of caustic burns, especially when deep injuries are present, due to the presence of scar tissue. After the treatment of initial complications and after an initial endoscopic evaluation, a few preventive measures can be decided to protect the upper part of the gastrointestinal tract. These measures include complete parenteral nutrition for some, and calibrating nasogastric tube for others; corticosteroid treatment is discussed. When stenosis is present, endoscopic dilatations can be performed. If they failed or instead of them, surgical replacement can be proposed with gastro or coloplasty. Resection of burned oesophagus prevents the risk of mucocele or cancer. PMID- 1598531 TI - [Sidelights on the history of the surgery of congenital cardiopathies]. PMID- 1598532 TI - [Chronic renal failure. Etiology, physiopathology, clinical, diagnosis, therapeutic principles]. PMID- 1598533 TI - [Non-traumatic meningeal hemorrhage. Etiology, diagnosis, course, prognosis, principles of treatment]. PMID- 1598534 TI - [Abdominal aortic aneurysm. Physiopathology, diagnosis, complications, principles of treatment]. PMID- 1598535 TI - [Iron deficiency. Etiology, physiopathology, diagnosis, principles of treatment]. PMID- 1598536 TI - [Hematuria in children. Diagnostic orientation]. PMID- 1598537 TI - [Hypertensive retinopathy. Diagnosis, course, prognosis]. PMID- 1598538 TI - [Idiopathic thrombopenic purpura. Physiopathology, diagnosis, course, principles of treatment]. PMID- 1598539 TI - [Mortality and morbidity of children. Definitions, main causes according to age, obligatory health tests, institutions of management]. PMID- 1598540 TI - [Genital prolapse. Physiopathology, diagnosis]. PMID- 1598541 TI - [Implantology: the consensus]. PMID- 1598542 TI - [Dental caries, urinary fluorides and enamel opacities]. AB - The aim of this study was to analyse with different statistic models the relation between fluoride urinary concentration, fluorosis and dental caries in terms of water fluoridation. 3237 schoolchildren aged 5 to 21 years were examined by a single dentist in accordance with the guidelines of the World Health Organization and following the standardized system for diagnosing, recording and analyzing dental caries data of Moller & Poulsen (1973). The index of Thylstrup & Fejerskov (1978) was applied to measure the prevalence and severity of dental fluorosis. Urinary fluoride concentration in 3022 children and water fluoride concentration were measured. The results of this study show a close relation between a high percentage of urinary fluoride, the presence of opacities and a low caries index. PMID- 1598543 TI - Mutans streptococci and their specific oral target. New implications to prevent dental caries? AB - Over the past 25 years collection and analysis of clinical, dietary and microbiological data have led to the conclusion that caries is a bacterial infection, initiated by mutans streptococci which can be transmitted within a family by saliva. Bacteria attach themselves selectively to various oral surfaces. In order to inhabit the mouth mutans streptococci require the presence of teeth. The targets of the odontopathogens (tooth hard substances and gingival sulcus) appear into the oral cavity on a "peculiar" way: these surfaces and tissues are not exposed to bacterial colonization from birth as skin and mucosa. Teething starts 8 +/- 2 months after birth at which age the infant's antibody dependent defence system is physiologically weak. Teeth erupt slowly during the night, at a period of least intraoral activity. Theoretically, streptococcal colonization can begin as soon as a few mm2 of incisal edges of primary teeth become visible. The earlier the establishment of mutans streptococci in the plaque of the primary teeth, the earlier and more extensive is the caries development. These aspects might open new possibilities for the prevention of the dental diseases, provided that means are found by which the primary colonization can be hindered or postponed. PMID- 1598544 TI - [Composite inlays: clinical and scanning electron microscopic research after a 1 year functional period]. AB - 24 composite inlays placed and documented for post-graduate education purposes in 1990 were reassessed clinically and by means of SEM. The clinical examination after 1 year of clinical service gave excellent results. The quantitative SEM evaluation of the marginal adaptation in the replicable areas revealed 6.6% of marginal gaps at the tooth/cement- and 27.1% at the cement/inlay-interface. To be able to compare these findings to the initial situation, additional five inlays were placed and examined in the SEM immediately after placement. This group exhibited next to gap-free margins. The results were selectively analyzed according to fabrication technique, type and localization of the restorations. No significant difference was found among molars and premolars. On the other hand, higher percentages of marginal gaps at the cement/inlay interface were observed with multi-surfaced, indirect lab-made inlays. PMID- 1598545 TI - [The reproducibility of arrow-point registration in full-dentition subjects depending on the recording material]. AB - The reproducibility of the intraoral central bearing point method was measured in 46 dentate subjects with a healthy stomatognathic system. Nine complete registrations were carried out on each volunteer, while three different materials were used for fixing the upper to the lower jaw. The occlusal records were examined in the condylar area on a specially designed articulator. Two therapists took part in this study. The shifts of the condylar spheres in all three spatial directions were found as follows: Ramitec 0.14 +/- 0.16 mm, Super-Bite 0.15 +/- 0.14 mm and Bite Compound 0.15 +/- 0.16 mm. The movements of the condylar spheres in space were calculated. They amounted to 0.28 +/- 0.23 mm when using Ramitec, 0.28 +/- 0.20 mm when using Super Bite and 0.31 +/- 0.23 mm when using Bite Compound. Statistically, the differences between the data of the three materials were not significant. Also, the results of our random sample were independent of the therapist. PMID- 1598546 TI - [The erosion of dental hard substance. Its epidemiology, clinical appearance, risk factors and preventive rules]. PMID- 1598547 TI - [Ceramic inlays as lateral tooth restorations]. PMID- 1598548 TI - [The position of dental implantology in 1991]. PMID- 1598550 TI - [Practical hygiene: a course for dentists and their assistants]. PMID- 1598549 TI - [The prevention of bacterial endocarditis. Interview by Benedikt Maeglin]. PMID- 1598551 TI - [The problems of light polymerization--new equipment and information of need]. PMID- 1598552 TI - [The radiological evaluation of autotransplants]. AB - The purpose of the present study was to investigate the radiological results of 40 autotransplantations (20 molars and 20 premolars) performed in the Orthodontic Department of the University of Geneva between 1979 and 1990. The sample demonstrated persistence of pulp vitality and continuous root growth, followed however in most cases by ankylosis and replacement root resorption. The data were in accordance with previous published studies and point out an ideal developmental stage for molar and premolar transplantation to ensure pulpal and periodontal survival. PMID- 1598553 TI - [How do occlusion disorder and stress influence cybernetic masticatory control?]. AB - Chewing forces were registered and compared in three subjects under normal conditions as well as in presence of occlusal interferences, and under stress. Biting force, blood pressure, and concentration of blood catecholamines were measured. Psychic stress was induced by demanding reactions on a test machine. In the presence of occlusal interferences, no significant increase in biting force was recorded. However, the biochemical analysis documented that biting forces appeared to be no longer under local control, but, increased up to 600% when the level of stress was raised. This study confirms the importance of stress as an etiologic factor in masticatory dysfunction. PMID- 1598554 TI - Periodontal conditions in Swiss Army recruits. AB - The purpose of the present study was to assess the oral hygiene and periodontal conditions of a young male population representative for Switzerland. 757 Swiss Army recruits were examined for their oral health status including the assessment of Plaque Index (PlI), Retention Index (RI) and Sulcus Bleeding Index (SBI) as well as Probing Depth (PD) and Loss of Probing Attachment (LA). All the teeth of the right maxillary and mandibular dental arch were evaluated on four aspects. One recruit yielded a status of juvenile periodontitis and was excluded from further analysis. 2.3% of the teeth had been lost, mainly as a result of orthodontic therapy. Mean PlI and SBI for all 756 recruits approximated 0.6, while the mean RI was around 0.1. The mean PD was 2.3 mm, and the mean LA of 0.9 mm was measured. PD and LA were slightly higher on proximal than on buccal or oral aspects. Site specific analysis for all parameters are presented. Since only 0.4% of the recruits showed probing depths of greater than or equal to 5 mm and only 1% of the subjects showed LA greater than or equal to 4 mm on any surfaces it may be concluded that severe signs of chronic adult periodontitis are absent in 99% of young male Swiss citizens. PMID- 1598555 TI - [Light polymerization equipment. Equipment types, functional operation, disinfection and technical upkeep]. PMID- 1598556 TI - [Light polymerization. The principles and practical tips for its correct use]. PMID- 1598557 TI - [The overdenture and GTR technic. The treatment of periodontally damaged overdenture-abutment teeth using a modified GTR technic--2 pilot cases]. PMID- 1598558 TI - [The amalgam today--the school of thought of the Basel Institute]. PMID- 1598559 TI - [The declaration of principle of the Federation Dentaire Internationale (FDI) on amalgam]. PMID- 1598560 TI - Possible origins of AIDS. PMID- 1598561 TI - Possible origins of AIDS. PMID- 1598562 TI - Museums cut research in hard times. PMID- 1598563 TI - Smithsonian Institution: bracing for bad news. PMID- 1598564 TI - World agriculture. Researchers score victory over pesticides--and pests--in Asia. PMID- 1598565 TI - Gene patents. Scientists voice their opposition. PMID- 1598566 TI - Congress sends a message. PMID- 1598567 TI - Fetal tissue. Banking for transplantation research. PMID- 1598568 TI - Time for a brain landing. PMID- 1598569 TI - Faint praise for science reporting. PMID- 1598570 TI - Paleoanthropologists launch a society of their own. PMID- 1598571 TI - Conodonts: a major extinct group added to the vertebrates. PMID- 1598572 TI - A transcriptional enhancer whose function imposes a requirement that proteins track along DNA. AB - Transcriptional regulation of the bacteriophage T4 late genes requires the participation of three DNA polymerase accessory proteins that are encoded by T4 genes 44, 62, and 45, and that act at an enhancer-like site. Transcriptional activation by these DNA replication proteins also requires the function of an RNA polymerase-bound coactivator protein that is encoded by T4 gene 33 and a promoter recognition protein that is encoded by T4 gene 55. Transcriptional activation in DNA constructs, in which the enhancer and a T4 late promoter can be segregated on two rings of a DNA catenane, has now been analyzed. The ability of an interposed DNA-binding protein to affect communication between the enhancer and the promoter was also examined. Together, these experiments demonstrate that this transcription-activating signal is conveyed between its enhancer and a T4 late promoter by a DNA-tracking mechanism. Alternative activation mechanisms relying entirely on through-space interactions of enhancer-bound and promoter-bound proteins are excluded. PMID- 1598573 TI - Presence of the earliest vertebrate hard tissue in conodonts. AB - From histological investigations into the microstructure of conodont elements, a number of tissue types characteristic of the phosphatic skeleton of vertebrates have been identified. These include cellular bone, two forms of hypermineralized enamel homologs, and globular calcified cartilage. The presence of cellular bone in conodont elements provides unequivocal evidence for their vertebrate affinities. Furthermore, the identification of vertebrate hard tissues in the oral elements of conodonts extends the earliest occurrence of vertebrate hard tissues back by around 40 million years, from the Middle Ordovician (475 million years ago) to the Late Cambrian (515 million years ago). PMID- 1598574 TI - Functional specialization of olfactory glomeruli in a moth. AB - The specific function of the glomerular structures present in the antennal lobes or olfactory bulbs of organisms ranging from insects to humans has been obscure because of limitations in neuronal marking methods. By tracing individual neurons in the moth Agrotis segetum, it was determined that physiologically distinct types of pheromone receptor neurons project axons to different regions of the macroglomerular complex (MGC). Each glomerulus making up the MGC has a specific functional identity, initially processing information about one specific pheromone component. This indicates that, at least through the first stage of synapses, olfactory information moves through labeled lines. PMID- 1598575 TI - High-efficiency expression and solubilization of functional T cell antigen receptor heterodimers. AB - The T cell receptor (TCR) zeta chain was attached to the TCR alpha and beta extracellular domains to induce efficient expression of alpha beta heterodimers that can recognize complexes of antigen with major histocompatibility complex (MHC) molecules. Chimeric constructs expressed in RBL-2H3 cells were efficiently transported to the cell surface uniquely as disulfide-linked heterodimers. Transfectants were activated by specific antigen-MHC complexes, which demonstrated that the expressed alpha beta was functional and that CD3 was not required for antigen-MHC binding. Constructs with thrombin cleavage sites were efficiently cleaved to soluble disulfide-linked heterodimers. Thus, attachment of TCR zeta domains and protease cleavage sites to TCR alpha and beta induces expression of demonstrably functional heterodimers that can be solubilized. PMID- 1598577 TI - Sparse population coding of faces in the inferotemporal cortex. AB - How does the brain represent objects in the world? A proportion of cells in the temporal cortex of monkeys responds specifically to objects, such as faces, but the type of coding used by these cells is not known. Population analysis of two sets of such cells showed that information is carried at the level of the population and that this information relates, in the anterior inferotemporal cortex, to the physical properties of face stimuli and, in the superior temporal polysensory area, to other aspects of the faces, such as their familiarity. There was often sufficient information in small populations of neurons to identify particular faces. These results suggest that representations of complex stimuli in the higher visual areas may take the form of a sparse population code. PMID- 1598576 TI - Prevention of autoimmune diabetes in the BB rat by intrathymic islet transplantation at birth. AB - Spontaneous diabetes in the BioBreeding (BB) rat, like human type I diabetes, results from the destruction of pancreatic islets by autoreactive T lymphocytes recognizing beta cell-specific antigens. T cell tolerance is in part mediated by interactions of maturing thymocytes with antigens expressed in the thymic microenvironment; islets were therefore implanted into the thymus of neonatal diabetes-prone BB rats to determine whether exposure of T cell precursors to beta cell antigens could influence the development of diabetes. This treatment completely prevented diabetes and insulitis in the native pancreas. The effect may be the result of specific modulation of diabetogenic T cells maturing in an islet-bearing thymus. PMID- 1598578 TI - Identification of a prenylation site in delta virus large antigen. AB - During replication, hepatitis delta virus (HDV) switches from production of small to large delta antigen. Both antigen isoforms have an HDV genome binding domain and are packaged into hepatitis B virus (HBV)-derived envelopes but differ at their carboxy termini. The large antigen was shown to contain a terminal CXXX box and undergo prenylation. The large, but not the small, antigen formed secreted particles when expressed singly with HBV surface antigen. Mutation of Cys211 in the CXXX box of the large antigen abolished both prenylation and particle formation, suggesting that this site is important for virion morphogenesis. PMID- 1598579 TI - Nondissociation of GAL4 and GAL80 in vivo after galactose induction. AB - Transcription of galactose-inducible genes in yeast is regulated by interaction between the activator protein GAL4 and the negative regulatory protein GAL80. It has been suggested that GAL80 binds to and represses GAL4 under uninduced conditions and dissociates from GAL4 on induction. However, the possibility that GAL80 remains associated with GAL4 after induction has not been ruled out. Experiments to discriminate between these two models were performed and revealed that GAL80 stays bound after induction. PMID- 1598580 TI - Congressional pork versus peer review. PMID- 1598581 TI - NIH presence shrinks at AIDS meeting. PMID- 1598582 TI - Making converts for condoms. PMID- 1598583 TI - A new take on anthropoid origins. PMID- 1598584 TI - How the brain 'sees' borders where there are none. PMID- 1598585 TI - An about-face for modern human origins. PMID- 1598586 TI - Epidemic cholera in the Americas. PMID- 1598587 TI - Oxytocin gene expression in rat uterus. AB - The neurohypophyseal hormone oxytocin (OT) is the most potent uterotonic agent known and is used to induce labor. Yet, endogenous circulating OT appears not to participate in the induction of labor. As shown here, the finding of OT messenger RNA and peptide in the uterus suggests a solution for this paradox. During gestation, rat uterus OT messenger RNA increased more than 150-fold and, at term, exceeded hypothalamic OT messenger RNA by 70-fold. Thus, during parturition, OT may act primarily as a local mediator and not as a circulating hormone. PMID- 1598589 TI - [Effects of stimulation of renal afferent nerve on renal excretion of water, sodium and potassium]. AB - The present study was designed to investigate the effect of stimulation of the renal afferent nerve (RAN) on renal excretory function and its mechanism. In pentobarbital-anesthetized, sino-aortic denervated and vagotomized (SAD+VD) cats, stimulation of the RAN caused a significant rise in arterial pressure. In the denervated kidney urine volume (Vu) and sodium excretion (UNa V) were greatly increased, no changes in potassium excretion (UK V) and glomerular filtration rate (GFR) were observed. In the innervated kidney, UNa V was greatly increased, but Vu, UK V and GFR were not different from those observed during the control period. When arterial pressure was held constant at the control level, stimulation of the RNA reduced the Vu, UK V of both the innervated and denervated kidneys and GFR in the innervated but not in the denervated kidney. Transection of spinal cord at C7 level did not abolish the changes in Vu, UNa V, and UK V in the innervated kidney, but completely eliminated the changes in the excretory function in the denervated kidney. These data suggest that when arterial pressure is controlled, stimulation of the RAN causes a decrease in Vu, UNa V, UK V in SAD+VD cats and that these responses in the innervated kidney can be performed at the spinal level. PMID- 1598588 TI - Galactose oxidation in the design of immunogenic vaccines. AB - Potent immunological adjuvants are urgently required to complement recombinant and synthetic vaccines. However, it has not been possible to derive new principles for the design of vaccine adjuvants from knowledge of the mechanism of immunogenicity. Carbonyl-amino condensations, which are essential to the inductive interaction between antigen-presenting cells and T helper cells, were tested as a target for the enhancement of immune responses. Enzymic oxidation of cell-surface galactose to increase aminereactive carbonyl groups on murine lymphocytes and antigen-presenting cells provided a potent, noninflammatory method of enhancing the immunogenicity of viral, bacterial, and protozoal subunit vaccines in mice. PMID- 1598590 TI - [A modified microanthrone method for the determination of inulin on nanogram scale]. AB - The establishment of a method of determining minute amount of inulin on nanogram scale is essential for applying micropuncture technique to kidney research. In this experiment, we modified a classical microanthrone method which was used by Dirks et al. to determine inulin contained in tubular fluid. A spectrophotometer was installed with a special microcuvette to suit the colorimetry of 10 microliters solution. Linear relation between inulin concentration and absorption was observed in the range of inulin concentration from 2 to 32 nl per 10 microliters anthrone reagent. The accuracy of this microanthrone method was evaluated with inulin recovery test, the mean recovery rate being 101.2 +/- 3.5%. Since tubular fluid did not interfere with the determination of inulin, the tubular fluid which contained inulin could be added directly to anthrone reagent in actual practice. The mean single nephron glomerular filtration rate measured with this modified microanthrone method in 21 rats was 34.9 +/- 1.8 nl/min, which coincided well with the values reported in literature. The results indicate that the measurement of inulin with the above-mentioned microanthrone method is reliable and suitable for the micropuncture study. PMID- 1598591 TI - [Pressor response to glutamate-injection into hypothalamic paraventricular nucleus and its relation to pressor response of locus coeruleus and depressor response of A1]. AB - In urethane-anesthetized, tubocurarine-immobilized and artificially ventilated rats, microinjection of L-glutamate (Glu) into hypothalamic paraventricular nucleus (NPV) or locus coeruleus (LC) induced a pressor response. The LC-pressor response could be attenuated by preinjection of phentolamine or propranolol into bilateral NPV; Preinjection of phentolamine or bicuculline into bilateral NPV could also attenuate the depressor effect of A1-excitation by Glu, but preinjection of propranolol had no such effect; suggesting that the LC-pressor or A1-depressor effect is mediated partly by NPV, and GABAergic inhibitory interneurons in NPV may be involved in A1-depressor response. PMID- 1598592 TI - [Nucleus fastigius-rostral ventrolateral medulla system is involved in vestibular depressor and bradycardia responses]. AB - In urethane-anesthetized, tubocurarine-immobilized and artificially ventilated rats, microinjection of L-glutamate (Glu) into the nucleus fastigius or nucleus vestibular superior caused a depressor and bradycardia response. Both the depressor and bradycardia responses of the nucleus fastigius and nucleus vestibularis superior were blocked by preinjection of bicuculline (a GABAergic receptor blocker) into the rostral ventrolateral medulla. And the cardiovascular response-induced by excitation of the nucleus vestibularis superior could also be blocked by procaine-injection into the nucleus fastigius. These results indicate that the vestibular depressor and bradycardia response was induced via the nucleus fastigius rostral ventrolateral medulla system. Intravenous injection of methyl atropine also markedly attenuated the cardiovascular response of the nucleus fastigius, indicating that the vagus nerve is also involved in the depressor and bradycardia response of vestibulo-fastigial excitation. PMID- 1598593 TI - [Changes in beta-endorphin and its messenger RNA in pituitary, hypothalamus, lymphocytes and blood plasma during cold acclimation of rats]. AB - Changes of beta-endorphin (beta-EP) and its mRNA in pituitary (P), hypothalamus (HT), lymphocytes (LC) and blood plasma (BP) during cold acclimation of SD male rats were studied by beta-EP mRNA dot blot, RP-HPLC and beta-EP radio-immunoassay (RIA). Experimental results showed: (1) After cold-exposure for 1 week pituitary beta-EP mRNA increased significantly with the appearance of stimulated cellular immune function. (2) beta-EP mRNA in hypothalamic immune center and peripheral LC increased when cold acclimation of animals was established for a cold exposure of 2 weeks (C2W). (3) From C2W onward, plasma beta-EP also continued to increase, indicating an augmented state of cellular immune function. As LC and plasma beta EP product continued to show increase, pituitary beta-EP mRNA content recovered to control level from C2W onward possibly due to a feedback mechanism through LC P-HT axis. PMID- 1598594 TI - [A study of the protective mechanism of hepatic stimulator substance against experimental acute liver failure in mice]. AB - In our previous work we have demonstrated a protective effect of hepatic stimulator substance (HSS) on experimental hepatic injury in mice. The underlying mechanism of this effect was further investigated with the following results: (1) HSS could significantly increase the CCl4-induced decrease of membrane fluidity of hepatic plasmalemma, mitochondria and microsomes to the control level. (2) HSS could decrease the liver melondialdehyde contents of CCl4-intoxicated mice. (3) HSS could restore the liver glutathione contents lowered by CCl4-intoxication. (4) HSS stimulated regeneration of liver, enhanced DNA synthesis of hepatocytes and increased 3H-TdR incorporation into DNA. According to the results mentioned above, we proposed that HSS should have an antioxidative effect on the hepatic membrane lipid peroxidation which was increased by free radicals produced by CCl4. In addition, HSS might increase antioxidative ability of hepatocyte and stimulate the proliferation of hepatocytes. These protective mechanisms might act in a concordant manner. PMID- 1598595 TI - [Effect of carbon tetrachloride intoxication on leakage of intracellular potassium in regenerating rat hepatocytes in vitro]. AB - Leakage of intracellular potassium and GPT in normal rat hepatocytes exposed to 10, 15 and 20 mmol/L of carbon tetrachloride (CCl4) in vitro was determined at 5, 10, 15 and 20 min after cell intoxication. Both of the intracellular potassium and GPT were clearly dose- and time-dependent with CCl4, but the leakage of intracellular potassium is a more sensitive index to indicate cell injury than the later. The percent change of intracellular potassium in regenerating rat hepatocytes 20 min after CCl4 (15 mmol/L) intoxication was markedly reduced than that in normal rat. This finding indicates that regenerating hepatocytes are resistant to CCl4 hepatotoxicity in vitro, and its mechanism presumably is due to a higher stability of regenerating liver cell membrane. PMID- 1598596 TI - [Changes in cardiac contractility induced by stimulation of hypothalamic ventromedial nucleus]. AB - Experiments were performed on anesthetized cats to observe the effect of electrical stimulation of the hypothalamic ventromedial nucleus (VMH) on cardiac contractility as judged by the change in LVSP, dp/dtmax, Vmax, P-dp/dt, P lndp/dt. Electrical stimulation of VMH induced an augment response in cardiac force, while stimulation of an area between VMH and the third ventricle led only to a decrease in cardiac contractile force. All these changes were not accompanied by significant changes in heart rate and unaffected by bilateral vagotomy. The present experiment indicates that the inotropic and chronotropic regulation centers of cardiac function exist in different hypothalamic areas. PMID- 1598597 TI - [Effects of different thyroid states on 5-HT1A receptor in adult rat brain]. AB - The effects of dysthyroidism on central 5-HT1A receptor subtype in adult Wistar rats were investigated. Hyperthyroidism and hypothyroidism were respectively produced with the administration of T3 and propylthiouracil (PTU) via gavage for 2 weeks. Heart rate, oxygen consumption, anal temperature and plasma T3 concentration were increased in hyperthyroid rats and decreased in hypothyroid rats significantly. Radioligand binding assay showed that the specific binding of [3H] 8-hydroxy-2-(di-n-propylamino) tetralin ([3H] 8-OH-DPAT) at 0.6 nmol/L concentration was highest in hippocampus, next in cerebral cortex, and lowest in hypothalamus, brain stem and corpus striatum in euthyroid rats. Hyperthyroidism increased the binding significantly in hippocampus but decreased in cortex. No change was found in the other brain regions. Scatchard analyses revealed that the Bmax was increased in hippocampus and decreased in cortex, whereas the KD was not consistently affected in hyperthyroid rats in comparison with that in euthyroid rats. However, there were no significant changes mentioned above in all these brain regions of hypothyroid rats. Our results indicate that there seems to exist an imbalance of the serotonergic activity mediated via 5-HT1A receptor between hippocampus and cerebral cortex in hyperthyroids. This might be one of the mechanisms leading to psychoneural disorders in hyperthyroidism. PMID- 1598598 TI - [Correlation between synaptic protein phosphorylation in hippocampi and shuttle box avoidance behavior]. AB - The present investigation was undertaken to detect whether protein phosphorylation levels of hippocampal synaptosomes in mice trained on shuttle box avoidance task would show some changes. The synaptosomes were prepared at different times after the conclusion of training and labelled with gamma-32P-ATP for in vitro determination. The results are as follows: (1) No significant differences were found in the phosphorylation of synaptosomal proteins in different brain areas in normal mice before training. (2) Immediately after the conclusion of shuttle box avoidance task there appears a correlation between protein phosphorylation levels in hippocampal synaptosomes and the degree of success of training. (3) 24 h after the completion of training the above relationship is more significant, and protein phosphorylation levels of right hippocampus in Good Score Group is markedly higher than that of left one, but in the Inferior Score Group, the left-right difference is reverse. The formation of such asymmetry in protein phosphorylation in hippocampi is unknown. These data indicate that the synaptic protein phosphorylation in hippocampi might be a molecular mechanism of acquisition. PMID- 1598599 TI - [Effect of electrical and L-glutamate stimulation of nucleus raphe obscurus on phrenic nerve activity in rabbits]. AB - Experiments were performed on 45 urethane-anesthetized, vagotomized and spontaneously breathing rabbits. By electrical stimulation of or microinjection of L-glutamate into nucleus raphe obscurus (NRO), the following results were observed: (1) A long stimulus train (50-200 microA, 100Hz, 4-6 s) delivered to NRO resulted in a decrease in integrated phrenic amplitude (IPA) or complete cessation of phrenic nerve discharge. The decrease of IPA was dependent upon current intensity and frequency of stimulation. (2) Short train stimulation (100 200 microA, 50-100 Hz, 5-20 pulses) delivered to NRO during the inspiratory phase terminated this phase prematurely, i.e., inspiratory off-switch (IO-S). The IO-S time varied according to the current intensity and the delivery time of stimulation in the inspiratory phase. (3) Microinjection of L-glutamate (1 mol/L, 1 microliter) into NRO caused a transient depression of phrenic nerve activity followed by a shortening of inspiratory time (Ti) and a lengthening of expiratory time (Te). PMID- 1598600 TI - Current diagnosis and treatment of rhinosinusitis--functional endoscopic sinus surgery (FESS) PMID- 1598601 TI - Medical intensive care in the general hospital. PMID- 1598602 TI - Medical intensive care unit utilization in an acute teaching hospital. AB - To ascertain the profile of medical intensive care unit (MICU) utilization in the Singapore General Hospital, a prospective survey studying 162 consecutive patients admitted to MICU was conducted over a four-month-period spanning September through December 1990. While there was no racial predilection, male admissions (n = 98) outnumbered female (n = 64) by a ratio of 3:2. Male admissions averaged 56.7 +/- 1.9 years (mean +/- SEM) vs 56.4 +/- 2.69 years in female (p = 0.98). Sepsis comprised 25.3% (n = 41) of admissions during this period of which chest infection (n = 26) made up 63%. The superinfection rate was 3% comprising colonization of endotracheal and peritoneal dialysis tubes by Candida and Acinetobacter. There was a surprisingly high number of culture negative infections. These amounted to 43.9% (n = 18) out of 41 admissions for sepsis as the primary indication and 57.1% of admissions in which sepsis was an accompaniment of the main indication. The mean duration of ICU stay was 7.17 +/- 1.5 days for sepsis vs 4.7 +/- 0.5 days for admissions other than sepsis. Although this did not reach statistical significance (p = 0.79) it corroborates the prevalent impression that patients with sepsis tend to require longer intensive care. The overall mortality was 37% (n = 60). The mortality for septic patients (42.5%) is alarmingly high. This contrasts with a mortality rate of 34.7% for non-septic patients. The issue of culture negative sepsis needs to be addressed. As it stands, septic patients stay longer than non-septic ones.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598603 TI - Mortality patterns in a medical intensive care unit. AB - We studied the mortality rate and patterns in a 6-bedded Medical Intensive Care Unit in a busy general hospital. We found a high mortality rate (26% in-ICU and 42% in-hospitalization) and that mortality was strongly associated with the following factors: cardiac arrest, respirator support, duration of stay in ICU, infection and the immunocompromised state. Lack of formal patient selection and entry criteria and Critical-Care Specialists may be contributing factors. PMID- 1598604 TI - The toxic strept syndrome: two case reports. AB - We describe two patients with group A beta hemolytic streptococcal septicemia from minor foci in the skin. They developed extreme toxemia, mental obtundation and multi-system organ failure associated with diffuse erythema. They both survived after appropriate antibiotic and intense supportive therapy. These are examples of the "toxic strept syndrome" which is similar to staphylococcal toxic shock. PMID- 1598605 TI - Outcome of very low birthweight neonates in a developing country: experience from a large Malaysian maternity hospital. AB - Between January 1989 to April 1990 (16 months), a prospective observational study was carried out on 329 consecutive very low birthweight (VLBW) less than or equal to 1500 grams) Malaysian neonates born in the Maternity Hospital, Kuala Lumpur before their first discharge from the hospital. The objectives of the study were to determine the common causes of early morbidity and mortality of this group of Malaysian neonates. The study shows that the incidence of Malaysian VLBW neonates was 9.9 per 1000 livebirths (95% confidence intervals 9.0 to 10.8). The mean duration of stay in the hospital was 19.3 days (SD = 21.4). One hundred and ninety-six (59.6 percent) of the VLBW neonates died. They accounted for 60 percent (196/334) of all neonatal deaths in the hospital during the study period. Mortality was significantly higher in neonates of birthweight less than 1000 grams (p less than 0.01) and of gestation of less than 33 weeks (p less than 0.001). The three most common clinical problems were respiratory distress syndrome (RDS) (72.6 percent), septicemia (28.0 percent) and intraventricular haemorrhage (IVH) (21.9 percent). Death occurred in 71.1 percent of the septicemic patients. The most common causative organisms of septicemia were multiresistant klebsiella (52.3 percent) and multiresistant acinetobacter (14.7 percent). RDS (33.2 percent), septicemia (29.6%) and IVH (17.9 percent) were the three most common causes of death. Improvement in the nursing staff situation and basic neonatal care facilities in this hospital and prevention of premature delivery could help to decrease morbidity and mortality in this group of neonates. PMID- 1598606 TI - Informed patient consent--historical perspective and a clinician's view. AB - Informed patient consent, in this day and age, is usually taken for granted, poorly understood, and inadequately practised. Historically, informed patient consent is relatively new to medical practice, as there was no such consent during the times of the ancient Egyptians, the ancient Greeks or Romans. The culture of individual rights as part of a social trend and evolution of human civilisation with landmarks such as the American Revolution two centuries ago also brought along greater patient awareness of their health and persons as well as their rights in the investigations, treatment and research of their illnesses. The rationale and elements in the practice of informed patient consent is part of this trend. However, there are moral and legal dilemmas involved. Discussion is needed, and though the practice of such consent may sometimes be difficult, the spirit of its application should never be compromised. PMID- 1598607 TI - Analysis of ras gene mutations in acute myeloid leukemia by the polymerase chain reaction and oligonucleotide probes. AB - In vitro deoxyribonucleic acid (DNA) amplification by the polymerase chain reaction (PCR) followed by hybridization with oligonucleotide probes were used to study ras gene mutations in acute myeloid leukemia (AML). The DNA of 30 AML patients at presentation of the disease at the University of Malaya Hospital, Kuala Lumpur were screened for ras gene mutations in codons 12, 13 and 61 of the N-ras, K-ras and H-ras genes. Four patients (13.3%) had ras gene mutations. They were all below their early thirties in age. Of the four patients with ras gene mutations, three were M3 and one was M4 according to the French American British (FAB) classification of AML. PMID- 1598608 TI - Transvenous radiofrequency catheter ablation of atrioventricular accessory pathways. AB - Transvenous delivery of radiofrequency energy is an attractive new technique in nonsurgical treatment of cardiac arrhythmias. We used radiofrequency catheter ablation in two patients with tachycardias complicating the Wolff-Parkinson-White syndrome. The first patient was a 28-year-old male who had suffered cardiac arrest from rapid preexcited atrial fibrillation (shortest RR interval of 180 ms) due to a left anterolateral free wall accessory pathway. The accessory pathway was mapped by means of positioning a 7F quadripolar catheter with a 4 mm tip to obtain the shortest atrial to ventricular timing during preexcited sinus rhythm. Unmodulated radiofrequency energy (750 KHz) was applied unipolarly between the distal pole of the catheter against an indifferent plate at the back. Using an applied energy of 30W, this resulted in the disappearance of both anterograde and retrograde conduction. The second patient was a 26-year-old man with concealed left posterolateral pathway. This was ablated at the site which corresponded to the shortest ventriculatrial timing during sustained atrioventricular reciprocating tachycardia. There was no complication from this procedure and both patients were discharged on the fourth day after the procedure and returned to work soon afterwards. Radiofrequency ablation is a safe and effective means for the treatment of paroxysmal supraventricular tachycardias. PMID- 1598609 TI - Attitudes to AIDS and sexual behaviour among a cohort of medical students in Singapore. AB - A survey conducted in 1990 among final year medical students found that most respondents had a good knowledge about AIDS and its routes of transmission. Among the 13.7% of respondents that were sexually active, it was noted that only 35% had used the condom before and that only 20% had used it in the most recent occasion of sexual intercourse. It was noted that only 30% of the sexually active had intention using the condom when they next have sexual intercourse despite the fact that 40% of them were having sexual intercourse with causal partners. Despite having a high knowledge of AIDS, medical students at the National University of Singapore have a low use of condoms. PMID- 1598611 TI - Psychiatric morbidity in the families of paranoid and non-paranoid schizophrenia patients. AB - A total of 1018 and 812 first degree relatives (FDR) of schizoprencies and controls respectively, were studied to find out the psychiatric morbidity in the families of paranoid and non-paranoid schizophrenia patients. The risk of schizophrenia and affective disorders was found to be independent of the probands subtype diagnosis. The risk for schizoid-schizotypal and paranoid personality disorders was found to be increased in the first degree relatives of paranoid schizophrenic, as compared to non-paranoid schizophrenic, thus suggesting that the psychopathology in the FDR may differ with the subtype diagnosis of the proband. PMID- 1598610 TI - The Mentakab hypertension study project. Part V--Drug compliance in hypertensive patients. AB - Poor compliance with drug treatment is a barrier to effective management of hypertension. Drug compliance behaviour of 168 patients were studied, their drug compliance was measured by the pill-counting method. The prevalence of non compliance with medication was 26%. Thirteen variables were examined for their association with compliance; these were age, sex, duration of hypertension since diagnosis, adequacy of blood pressure control, complexity of drug regimen and side-effect of drug, history of previous admission for hypertension related reason, patient's knowledge of hypertensive complications, patient's belief that drug was 'panas' or 'san', previous use of traditional treatment for hypertension, patient's fatalistic attitude, their social support and satisfaction with the health services. None of these variables were significantly related to compliance (p greater than 0.05) except adequacy of blood pressure control. The performance of patient self-report was compared with pill-count as a measure of drug compliance; it was poorly predictive of non-compliance (sensitivity = 71%, specificity = 50%). An inverse relationship was found between non-compliance with medication and patient subsequent drop-out rate. Patients who were compliant were more likely to remain on treatment and vice versa. As a measure of drug compliance, detection of drop-out compared well with pill-count (sensitivity 97%, specificity 66%, positive predictive value 89%, negative predictive value 88%). PMID- 1598612 TI - Pregnancy in patients with systemic lupus erythematosus. AB - The view that SLE in pregnancy is associated with poor maternal and perinatal outcome is generally accepted. Consequently, there is a mistaken but commonly held belief that termination of such pregnancies will safeguard maternal health. However, because of advances in diagnostic technology, improved antenatal and neonatal surveillance, wider treatment options and a clearer understanding of the pathological processes involved, such a view is no longer tenable. This article outlines the changes in obstetric practice that have made pregnancy in women with SLE a relatively safe process. In particular, it emphasizes the need for a multidisciplinary approach to caring for such pregnancies. It also draws out some of the experiences we have had with the management of such pregnancies in Singapore that will reinforce the view that women with SLE can reproduce safely and successfully given appropriate care. PMID- 1598613 TI - Psychological aspects of rheumatic diseases. AB - Psychological problems in rheumatic diseases are common and influence the maintenance of symptoms and management. The psychological and psychosocial aspect of rheumatoid arthritis and systemic lupus erythematosus are briefly described. An approach to psychological management and the role of the psychiatrist in rheumatology are considered. In addition to appropriate and adequate treatment of concomitant psychological disorders with drugs, psychosocial interventions and the use of other forms of therapy such as self-help groups are also invaluable. PMID- 1598614 TI - Broad complex tachycardia--supraventricular with aberrancy or ventricular tachycardia? PMID- 1598615 TI - Placental chorioangioma: a case report and review. AB - Placental Chorioangioma occurs in 1% of pregnancies and are generally asymptomatic. However, they are known to cause a number of complications which are detrimental to the mother, fetus or the neonate. A typical case where acute polyhydramnios precipitated premature labour and delivery of the fetus as a result of a large placental chorioangioma is presented. A brief review of the other possible complications are also included. PMID- 1598616 TI - Acute myocardial infarction after blunt chest injury. AB - A 20-year-old male sustained an inferior myocardial infarction following blunt chest trauma, after a motor vehicle accident. Though coronary arteriograms 9 months later were normal, LV angiography revealed severe hypokinesia of the inferobasal and diaphragmatic segments. The literature is reviewed with respect to mechanisms of injury, autopsy and angiographic findings and clinical outcome in this condition. PMID- 1598617 TI - Liver rupture in pregnancy: a typical case? AB - We report a patient who presented with abruptio placenta and hepatic rupture at 30 weeks gestation. The latter is a recognised but rare complication of pre eclampsia and eclampsia. The typical features of this entity as described in the literature and as seen in this patient are emphasized as increased awareness can lead to early diagnosis and better prognosis. PMID- 1598618 TI - Psychiatric syndromes in pernicious anaemia--a case report. AB - Surveys of psychiatric population had previously shown a high incidence of patients with low serum vitamin B12. A variety of psychiatric syndromes have been described, ranging from mild disturbance in mood state like depression to maniacal excitement; psychotic conditions like paranoid states and schizophrenia; and cognitive dysfunctions such as memory defect, delirium and dementia. A case of a 67-year-old Chinese lady suffering from pernicious anaemia, but presenting with prominent paranoid delusions is reported. Treatment with cyanocobalamine and anti-psychotic medication led to prompt resolution of her psychotic experience. Subsequently she developed a transient depressive syndrome which also responded well to a short course of antidepressant. PMID- 1598619 TI - [Sex differences in sudden infant death]. AB - In a group of 79 infants who died suddenly 65.8% were boys and 34.2% girls and in a control group of 56 infants who died from disease or injuries 53.6% were boys and 46.4% girls. The authors discuss the possibility that sudden infant deaths are one of the biological mechanisms which balance the predominance of births of male infants. PMID- 1598620 TI - [Water as a detecting agent in thin-layer screening of drugs]. AB - For detection of some selected drugs on a thin-layer sprinkling with water was used. White, well defined spots develop on a wet background, which after drying can be further identified by a specific colour reaction or extract for photometric identification. PMID- 1598621 TI - [Ethical and moral dilemmas in forensic medicine]. PMID- 1598623 TI - [Systems approach and pediatric psychiatry]. PMID- 1598624 TI - [The family placement of children]. PMID- 1598622 TI - [Practical experience in the use of HPTLC for drug screening]. AB - The authors give an account of practical experience with chromatography of drugs using HPTLC. As an indicator berberin hydrochloride or sulphate proved useful. The sandwich method was satisfactory as regards reproducibility of Rf values. PMID- 1598625 TI - [Family therapy and passage to the adult age]. PMID- 1598626 TI - [A certain solitude]. PMID- 1598627 TI - [Dimensions of psychiatric nursing care and theorization]. PMID- 1598629 TI - [Family therapy--a multiform practice]. PMID- 1598628 TI - [Some words about death]. PMID- 1598630 TI - [Private practice and systems therapy]. PMID- 1598631 TI - [Treatment of dementia states of the aged]. PMID- 1598633 TI - [Forgetfulness]. PMID- 1598632 TI - [Stimulation and rehabilitation of the senile dementia patient]. PMID- 1598634 TI - [Day hospital. A stimulation experience in cognition disorders in the aged]. PMID- 1598635 TI - [Families and aged parents]. PMID- 1598636 TI - [The role of nurses and psychiatric nurses at the end of the 19th century. Guarding, caring, innovating?]. PMID- 1598637 TI - [My life is a nightmare]. PMID- 1598638 TI - [Augmentation of hope in life: facts and perspectives]. PMID- 1598639 TI - [The process of dementia: current state of knowledge]. PMID- 1598640 TI - Environmental health issues in the 1990s. PMID- 1598641 TI - The role of the physician in environmental health. PMID- 1598642 TI - Environmental health officers--new challenges. PMID- 1598643 TI - The South African Forum for Radiation Protection. PMID- 1598644 TI - Morbidity among bathers exposed to polluted seawater. A prospective epidemiological study. AB - As the first phase of a major programme to develop epidemiologically derived recreational water quality criteria for South Africa, a preliminary epidemiological-microbiological study was conducted in Cape Town during February and March 1990. Serial trials were carried out at a clean and at a relatively polluted beach over weekends. Participants were recruited at the beach, at which time information on swimming status and sociodemography was obtained. This provided for a beach-going but non-swimming control group. Symptoms which developed subsequent to the beach visit were obtained by follow-up telephone interviews conducted 3-4 days later. Water samples collected on trial days both before and during maximum swimming activity, were analysed for enterococci, faecal coliforms, staphylococci, coliphages and F-male-specific bacteriophages. Significant differences in the indicator levels at the beaches were observed. An excess in gastro-intestinal, respiratory and skin symptoms were found among swimmers relative to non-swimmers at the polluted beach. Although not statistically significant, the results are suggestive of a relationship between swimming-associated illness and water quality. The study demonstrated the feasibility of the methodology and the results of the overall programme will form the basis for the development of epidemiologically derived recreational water quality criteria for South African beaches. PMID- 1598645 TI - Environmental health risks of toxic waste site exposures--an epidemiological perspective. AB - A general account is given of the problems of assessing the impact of human exposure to toxic waste sites, including the identification of truly exposed populations and of exposure pathways. Epidemiological studies of populations at risk are briefly reviewed and methodological problems summarised. These include the use of relatively weak study designs, inadequate exposure assessment and recall biases associated with symptom reporting among anxious residents living in the vicinity of waste sites. In South Africa, health risks associated with exposure to toxic waste sites need to be viewed in the context of current community health concerns, competing causes of disease and ill-health, and the relative lack of knowledge about environmental contamination and associated health effects. A nonspecific deterioration of health and well-being is more likely to result from waste site exposures than is overt clinical disease. Socially acceptable policies and controls may have to be based on criteria other than demonstrable ill-health. Detailed inventories and registries of the nature of disposed materials need to be maintained, sites of poorly controlled disposal in the past identified and selective environmental monitoring conducted. Epidemiological studies may be justified in situations where exposures well in excess of acceptable norms are demonstrated. An integrated national waste management policy for the country is urgently needed. PMID- 1598647 TI - Occupational and environmental epidemiology--similarities and contrasts. AB - There has been considerable growth in the disciplines of occupational and environmental epidemiology in recent years, with both fields having to deal with increasingly complex exposure profiles and adverse health outcomes. Environmental and occupational epidemiology as distinct from general epidemiology are compared and contrasted. Similarities and differences between the two fields are systematically discussed in terms of epidemiological peculiarities, study design characteristics, sampling procedures, exposure assessment, typical biases, problems in determining causation, ethical constraints, and implementation possibilities for research findings. There is a need in South Africa to provide adequate training to health professionals working in these fields, so that high quality research, which has the potential to contribute significantly to improvements in the health of workers and the general public, can be undertaken. PMID- 1598646 TI - Preliminary results of exposure measurements and health effects of the Vaal Triangle Air Pollution Health Study. AB - The aim of the Vaal Triangle Air Pollution Health Study is to assess the adequacy of South Africa's air pollution control programme to protect human health. It is a longitudinal study of children aged 8-12 years which will evaluate exposure and effects of outdoor and indoor air pollution levels on the health of more than 10,000 white and black children living in Vanderbijlpark, Sasolburg, Vereeniging, Meyerton, Randvaal, and the Sebokeng/Sharpeville areas (Lekoa), Transvaal, RSA. Extensive data on outdoor and indoor levels of air pollution as well as personal exposures to total suspended particulate matter were collected. Preliminary results indicate that the levels of particulate matter exceed the USA health standards. A health questionnaire administered to 10,187 white children indicated that during the past year 65.9% had suffered from upper respiratory tract illnesses (URI) such as sinusitis, rhinitis and hay fever and 28.9% from lower respiratory tract illnesses (LRI) such as bronchitis, chronic cough and chronic chest illnesses. Parents who perceived that the air pollution in the region is serious had a higher reporting rate of URI/LRI for their children than parents who considered the air pollution not to be serious (77.4% v. 56.8% respectively for URI and 24.1% v. 16.3% respectively for LRI). The effect of this recall bias will be evaluated in later analyses. A statistically significant higher prevalence of LRI was reported in children exposed to parental smoking (25.7% for households where both parents smoked v. 20.8% in households without parental smoking) (odds ratio (OR) 1.32 (1.2-1.5)).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598648 TI - Agrichemical hazards in the South African farming sector. AB - Agrichemicals are used extensively in agriculture in South Africa and throughout the world and may present serious health hazards. A review is made of their acute, sub-acute and chronic health effects with attention to the teratogenic and carcinogenic potential. Assessment of agrichemical toxicity is critically discussed. The limited data available on agrichemical poisoning in South Africa suggest that agrichemical poisoning is significantly under-reported and is potentially a major public health problem. Implications for the development of health policy affecting farm workers are outlined. PMID- 1598649 TI - Histologically diagnosed cancer in South Africa, 1987. AB - The National Cancer Registry collects information on cases of histologically diagnosed cancer via a country-wide network of private and public pathology laboratories. Minimal age-standardised incidence rates (ASIR, world standard) per 100,000, excluding basal and squamous cell skin cancers, for white, coloured and Asian males were 195.9, 76.2 and 82.9 respectively, and for females 161.8, 68.8 and 81.1 respectively. The oesophagus was the commonest site of cancer in black males, comprising 25.2% of all cancers in this group, and the cervix was the commonest site in black females (31.6%). Basal and squamous cell skin cancers were the leading cancers in white males (ASIR 191.9) and females (ASIR 96.9). Despite limitations, especially in data for blacks, rates for oesophageal, cervical and skin cancers rank among the highest in the world. The lung was the leading site of cancer in coloured males (ASIR 13.8) but this cancer is underestimated in all populations. Reasons for underestimation of cancer incidence include the use of non-histological methods for diagnosing cancer (cytology, radiographs, clinical examination) and variable access of populations, especially blacks and coloureds, to laboratory diagnostic facilities. PMID- 1598650 TI - Availability of environmental health services among blacks in urban and peri urban areas of South Africa. AB - Fundamental to primary health care is the need to provide adequate environmental health services to the population. Such services constitute primary prevention, and, under some circumstances, may have a greater impact on health than the provision of personal health services. This study aimed to assess the availability of environmental health services among blacks living in urban and peri-urban areas of South Africa. A stratified random sample of 800 households was selected. After discussions with the Urban Foundation, it was felt that the proportion of informal dwellings obtained (20%) underestimated the true figure, which was closer to 50%. For that reason estimates are presented for a range of values (20-50% informal dwellings). For environmental health services the percentage availability was 30-45% for reticulated water in the home; 18-29% for an inside flush toilet; and 48-62% for possession of a personal refuse receptacle. Data obtained on domestic fuel use indicated that 41-61% of households had electricity. General indicators of social class showed that 62% of households had a monthly income less than R400, and that 22-30% of mothers with children under 5 years of age had an educational level of less than Standard 5. All of the measures were substantially worse among people living in informal dwellings. The data indicate that urgent attention should be given to improving the foundations of primary health care, particularly by providing and giving attention to equity, intersectoral co-ordination and community participation in the provision of essential environmental health services. PMID- 1598651 TI - Endemic goitre among undernourished schoolchildren in eastern Caprivi, Namibia. AB - A cross-sectional study on a 20% random sample of 380 children, aged 6-18 years, from 8 primary schools in the Cuando River area of eastern Caprivi, Namibia, was done to determine the prevalence of goitre and to investigate related hormonal and nutritional factors. Of the children 34.5% had goitre. Reduced plasma free thyroxine concentrations in the more severely goitrous children, compared with matched non-goitrous children (P = 0.0007), implicated dietary iodine deficiency as the causative factor. Their diet was inadequate in energy and most nutrients according to World Health Organisation criteria. Retarded growth, indicated by their low body weight and height in relation to age, were observed in a large proportion (45.6-73%) of the children. These findings suggest that dietary iodine deficiency was the most likely cause for the endemic goitre in these children, who were predisposed to nutritional disorders by long-term undernourishment. PMID- 1598652 TI - Deaths from infectious parasitic diseases in South African adolescents, 1984 1986. PMID- 1598653 TI - Oesophageal cancer in three regions of South Africa. PMID- 1598654 TI - South African tick-bite fever complicated by severe encephalopathy. PMID- 1598655 TI - Absence of antibody to Cowdria ruminatum in sera from humans exposed to vector ticks. PMID- 1598656 TI - Nasogastric tube complications--a precautionary note. PMID- 1598657 TI - Ingestion of a laryngoscope light bulb during tracheal intubation. PMID- 1598658 TI - Psychological factors in epidermolysis bullosa. PMID- 1598659 TI - [Stereotactic convergent-beam irradiation: its current prospects based on clinical results]. AB - "Radiosurgery" is the term for a special concept in radiotherapy. It describes a percutaneous, stereotactically guided irradiation delivering a single high dose with collimated narrow beams. The precise stereotactic localization of the target point and a steep dose gradient outside the target volume allow the administration of high doses to a lesion without damage to adjacent normal tissue. Risk of necrosis, due to a dose volume relationship represents the limits of radiosurgery. Units for radiosurgery were designed at Stockholm using multiple external cobalt-60-gamma sources, at Boston operating with protons of a cyclotron, at Berkeley operating with helium ions accelerated by a synchrocyclotron. An attractive alternative to these complicated and expensive facilities is the use of a modified linear accelerator. At the German Cancer Research Center in Heidelberg such a system was developed and has been available for the treatment of patients since 1984. Though, data of over 100,000 patients with vascular malformations and cancer disease are available worldwide, the indication for this therapy is validated only for a minority of entities. In cases of inoperable arteriovenous malformations favourable results in achieving obliteration range between 60% and 100% were obtained. Median survival for solitary brain metastases with controlled, extracerebral tumor diseases were between nine and twelve months. Up to now, advantages of stereotactic irradiation for benign tumor masses could not be proven. Therefore, randomized trials should be initiated in this field, considering decisive improvements in local tumor control with techniques of microsurgery and fractionated, postoperative radiotherapy during the last few years. PMID- 1598660 TI - Long-term follow-up of 92 patients with locally advanced follicular or papillary thyroid cancer after combined treatment. AB - Between 1960 and 1988, 92 patients with a locally advanced follicular or papillary thyroid cancer have been treated with surgery and radiotherapy consisting of iodine-131 or external (ext RT) radiotherapy or both. Locoregional control in patients less than 38 years of age at diagnosis and in older patients with a papillary cancer and a macroscopically complete resection was 100% with or without ext RT. Locoregional control in patients 38 years of age or older and without palpable postsurgical residual mass was 89% with ext RT and 60% without. In patients with a palpable residual mass, one of ten treated with iodine-131 alone had a permanent local control compared to six of 14 treated with addition of ext RT. Published data concerning iodine-131 and ext RT in the treatment of locally advanced follicular or papillary thyroid cancer are discussed. Routine surgery in our region consists of a near total thyroid resection, followed by iodine-131 ablation of the remnant thyroid. In younger patients with a limited T4 tumour and complete resection, we do not use ext RT. In all older patients with a T4 tumour as well as in younger patients with an extensive T4 tumour, ext RT is added. PMID- 1598661 TI - [The disease coping of radiation cancer patients compared]. AB - Emotional well-being and physical complaints of 87 outpatients undergoing radiotherapy were compared with those of a variety of other patients. The emotional and physical status were assessed by a list of emotional symptoms (German: "Befindlichkeitsskala") [18] and a list of physical complaints (German: "Beschwerdeliste") [19]. Although they have to cope with a fair amount of physical strain, values of the "oncologic group" rank second lowest, outranked only by healthy controls. The results strengthen the hypothesis of an adaptive denial to cope with the strain of the treatment. In conclusion, concrete suggestions are made for the doctor-patient relationship. PMID- 1598662 TI - [The percutaneous irradiation of osteolytic bone metastases--a course assessment]. AB - Percutaneous radiotherapy is the most effective modality for treatment of metastatic bone cancer. Local irradiation improves overall quality of life by relieving pain in most patients. It also helps preventing complications as pathological fractures in lytic bone lesions by new bone formation. In a retrospective study on 100 patients, irradiated for lytic bone metastases, the radiotherapeutic effect on alleviation of pain and on recalcification rate was investigated. In our experience in 84% of the cases pain and disability associated with bone metastases could be decreased. 38% of the patients had complete relief of symptoms. A correlation between subjective therapy effect and histology of the primary tumor was not demonstrated. Remineralization was found in 67% of all irradiated skeletal areas (n = 137) (recalcification rate in breast cancer 77%, in bronchial carcinoma 27%, and in renal cell carcinoma 25%). After a total dose of 30 Gy reduction of the metastases-associated pain was achieved in 81% of the cases and remineralization was observed in 70% of the cases. PMID- 1598663 TI - [The optimization of patient positioning and irradiation-field documentation in irradiation in the neck-nose-throat area]. AB - The large mobility of head and neck requires, when irradiating in this area, positioning and fastening aids, which go beyond simple head bolsters or head moulds. This paper presented describes a positioning system developed by us for irradiating the neck-nose-throat area, which, due to its construction, consists of a non-slipping positioning ground plate and an individually adjustable masking system, which is physiological safe, can be proceeded quickly and exactly, is relatively inexpensive, and is accepted by patients without objections, furthermore since skin markings by drawing field limits onto the face mask are no longer necessary. Various technical aids allow the placement of satellites to spare those body parts which are not irradiated and to install compensators for the direction of radiation. An integrated cartridge mount enables in a simple way easy production of field control documentation photos. PMID- 1598664 TI - [Irradiation field controls by digital luminescence radiography]. AB - Since portal images taken with conventional X-ray films suffer from poor contrast and unsharpness due to the high energy of the radiation beam, scattered radiation, patient motion, and the large dimensions of the radiation source, comparison of portal images with simulation images is often difficult and time consuming. Therefore many efforts have been made to improve such images. The use of storage phosphors and electronic image post-processing provides a remarkable improvement of image quality with better delineation of anatomical landmarks in high contrast areas such as head, neck, and mediastinum, as well as in low contrast regions, i.e. abdomen and pelvis. PMID- 1598665 TI - [The surface dosage in the radiotherapy of a small breast carcinoma with 6-MV x rays. A contribution to quality assurance in radiotherapy]. AB - Radiation treatment of breast cancer with high-energy X-rays in breast conserving therapy tends to an under-dosage of the skin region. Results of our measurements with patients and in water demonstrate that the skin receives only 40% of the reference dose applying tangential opposed wedged fields with 6 MV X-rays. Doing so we must accept a dose inhomogeneity of about 60% in the target volume. That may cause an increased recurrence rate especially for superficially situated tumors and/or in the case of intraoperatively disseminated tumor cells. We show that utilizing bolus material of only 5 mm water equivalence on the skin above the tumor bed reduces the dose inhomogeneity to 8%. PMID- 1598666 TI - [The radiotherapy of Castleman's lymphoma]. AB - The angiofollicular lymphoid hyperplasia, first described by Castleman, is a benign lymphoma. The authors report a very rare case of Castleman lymphoma in the parotid gland. The tumor was successfully irradiated with 40 Gy fast electrons. Treatment planning and therapy monitoring were done by means of ultrasound and computed tomography. PMID- 1598667 TI - Lung tumour growth delay and normal tissue toxicity induced by three cytotoxic platinum drugs. AB - Single doses of the drug cisplatin and its analogues carboplatin and iproplatin were administered to tumour-bearing rats. The tumours used were two bronchial squamous cell carcinomas, that are part of a panel of experimental lung tumours developed at this institute. Cisplatin resulted in severe nephrotoxicity. Carboplatin and iproplatin were less nephrotoxic, but resulted in acute gastrointestinal and (probably) hematological toxicity. Carboplatin also caused late occurring liver damage. The responses of the tumours were compared at the level of maximum tolerated drug doses for early toxicity. The level of response was different for the two tumours. One was more sensitive to the drugs than the other. The effects of cisplatin and carboplatin were approximately similar. Iproplatin was less effective. Because cisplatin caused more severe late toxicity, it is concluded that carboplatin has the best therapeutic index for these two lung tumours. PMID- 1598668 TI - Decision making in management of critically injured patients. PMID- 1598669 TI - Decreased growth hormone levels in the catabolic phase of severe injury. AB - BACKGROUND: Human growth hormone (hGH) is a potent anabolic agent, which has profound effects on protein, carbohydrate, and lipid metabolism. The role of this primarily anabolic hormone in the severe catabolic state of trauma is not known. METHODS: In a group of young, obese, and elderly patients with multiple traumas, plasma hGH levels were measured in the catabolic "flow" phase of injury, once before and then after 4 to 6 days of nutritional support sufficient to match their initial loss of calories and nitrogen. RESULTS: A decreased hGH level was noted in the hyperglycemic and hypercatabolic injured state, particularly in victims of trauma who were young and not obese, compared to respective volunteers. A significant (p = 0.025) inverse relationship was observed between age and plasma hGH levels in this group of patients who had experienced trauma. Nutritional therapy improved the protein and fat metabolism but could not reverse to the normal state. In young patients who had experienced trauma and who were not obese, the hGH levels were significantly improved because of dietary intake, whereas in elderly patients or patients who were obese no change was noted. CONCLUSION: These results are consistent with less lipid mobilization and inefficient utilization of fatty acids in the elderly patients or patients who were obese who had abundant fat sources to spare. Elevation of hGH level by exogenous administration may improve the nitrogen economy and lipid mobilization, particularly so in the elderly patients or patients who were overweight. Our study supports the view that provision of adequate nutrition with daily administration of human hGH in the first week after trauma would enhance the metabolic status of the patient, resulting in reduced morbidity and earlier discharge from the hospital. PMID- 1598670 TI - Duodenoesophageal reflux and the development of esophageal adenocarcinoma in rats. AB - BACKGROUND: The carcinogenic effect of duodenoesophageal reflux, gastroesophageal reflux, and nitrosamines was studied in the rat esophagus. METHODS: Twenty male Sprague-Dawley rats underwent esophagogastroplasty to produce gastroesophageal reflux and 60 underwent duodenoesophageal anastomosis to produce duodenoesophageal reflux. Forty-three animals underwent no operation and acted as controls. Carcinogens known to produce squamous tumors in the rat esophagus (2,6 dimethylnitrosomorpholine [DMNM] or methyl-n-amylnitrosamine [MNAN]) were tested in each group. RESULTS: The rate of squamous carcinoma was 25% for rats with DMNM alone, 30% for rats with MNAN alone, and 20% for rats with induced gastroesophageal reflux plus DMNM. The rate of malignant change rose to 80% in rats with induced duodenoesophageal reflux and DMNM and 67% with duodenoesophageal reflux and MNAN. With duodenoesophageal reflux, 50% of tumors were adenocarcinoma, in contrast to 100% squamous differentiation of tumors in rats given the carcinogens with esophagogastroplasty or no operation. CONCLUSION: The presence of duodenoesophageal reflux increased the frequency and changed the histologic type of esophageal cancer in nitrosamine-treated rats. This indicates that duodenoesophageal reflux plays a role in the development of esophageal adenocarcinoma. PMID- 1598671 TI - Proposed classification of complications of surgery with examples of utility in cholecystectomy. AB - Lack of uniform reporting of negative outcomes makes interpretation of surgical literature difficult. We attempt to define and classify negative outcomes by differentiating complications, sequelae, and failures. Complications and sequelae result from procedures, adding new problems to the underlying disease. However, complications are unexpected events not intrinsic to the procedure, whereas sequelae are inherent to the procedure. Failures are events in which the purpose of the procedure is not fulfilled. We propose a classification of complications based on four grades: Grade I complications are alterations from the ideal postoperative course, non-life-threatening, and with no lasting disability. Complications of this grade necessitate only bedside procedures and do not significantly extend hospital stay. Grade II complications are potentially life threatening but without residual disability. Within grade II complications a subdivision is made according to the requirement for invasive procedures. Grade III complications are those with residual disability, including organ resection or persistence of life-threatening conditions. Finally, grade IV complications are deaths as a result of complications. To illustrate the relevance of the classification, we reviewed 650 cases of elective cholecystectomy. Risk factors for development of complications were determined, and the classification was also used to analyze the value of a modified APACHE II as a preoperative prognostic score. Both supported the relevance of the proposed classification. The advantages of such a classification are (1) increased uniformity in reporting results, (2) the ability to compare results of two distinct time periods in a single center, (3) the ability to compare results of surgery between different centers, (4) the ability to compare results of surgical versus nonsurgical measures, (5) the ability to perform adequate metaanalysis, (6) the ability to identify objective preoperative risk factors, and (7) the ability to establish preoperative prognostic scores. PMID- 1598672 TI - Autoimmune mechanisms in thromboangiitis obliterans (Buerger's disease): the role of tobacco antigen and the major histocompatibility complex. AB - This study is a continuation of our previous work that showed that patients with thromboangiitis obliterans (TAO; Buerger's disease) demonstrate a cell-mediated immune response to human artery type-specific collagens. To investigate the role of cigarette smoking in patients with TAO, cellular and humoral sensitivity was tested to a tobacco glycoprotein (TGP) antigen in 13 patients with Buerger's disease, 16 healthy smokers, and 12 nonsmoking healthy young male subjects. In this study, patients with Buerger's disease and healthy smokers had the same rate of cellular response to TGP, whereas nonsmokers did not respond. All three groups had a 30% to 40% measurable antibody response to TGP. If TGP has an immunologic role in the pathogenesis of TAO, an additional factor (or factors) may be operative. A specific genetic makeup may be one such factor, although at this stage other pathogenic mechanisms cannot be ruled out. Eleven patients with Buerger's disease and two control groups of 10 young healthy smoking male subjects and 12 young nonsmokers underwent histocompatibility leukocyte antigen (HLA) typing. Patients with Buerger's disease had a statistically significantly higher frequency of HLA-DR4 and a significantly lower frequency of the HLA-DRW6 antigen than had both control groups. Because similar findings have been reported in other autoimmune diseases, this observation may serve as further evidence that an autoimmune mechanism is involved in Buerger's disease. PMID- 1598673 TI - Orthotopic liver transplantation with a reduced-size graft: an ideal compromise in pediatrics? AB - This study retrospectively reviewed the results of 81 orthotopic liver transplantations in 72 pediatric patients with either a full-size graft (n = 41) or a reduced-size graft (n = 40) during a 4-year period. Two types of liver reduction were used to obtain a left lobe graft (n = 30) or a left lateral segment graft (n = 10). The choice of the reduction technique was based on two criteria: the donor/recipient body weight ratio and the transverse size of the recipient's abdomen. The patients who underwent transplantation with a reduced size graft were younger and smaller than those who received a full-size graft. The mortality rate of the candidates on the pediatric transplantation waiting list was 2.7% during the same period. The 3-year survival rate after elective transplantation was 85% and 75% in the full-size graft group and the reduced-size graft group, respectively (difference not significant). The use of reduced-size grafts was associated with higher amounts of red cell and fresh-frozen plasma transfusions after graft revascularization. The incidence of postoperative bleeding and bile leakage from the transected surface was low, whereas hepatic artery and biliary complications were less frequent in the reduced-size graft group than in the full-size graft group. At the time of follow-up, liver biochemical test results and quality of life were not different between the two groups. Despite the constraining technique and the increase in intraoperative blood loss, orthotopic liver transplantation with a reduced-size graft allows us to overcome the shortage of pediatric donors and improve the overall survival rate of children with end-stage liver disease. PMID- 1598674 TI - Management of ruptured abdominal aortic aneurysm and concomitant biliary sepsis. AB - Since 1984 three patients have been treated for a ruptured abdominal aortic aneurysm and acute biliary sepsis. The biliary tract disease included two cases of gangrene of the gallbladder, one with perforation. Two patients had cholangitis. All patients underwent repair of the ruptured aneurysm and cholecystectomy under the same anesthetic. Two individuals required common duct exploration: one at the time of the initial operation and the other 6 days later. Despite a high incidence of postoperative complications in these elderly men, all survived surgery and are alive and well after periods of 1 to 7 years. There have been no graft infections. PMID- 1598675 TI - Local excision of carcinoma of the rectum for cure. AB - During the past 10 years, we have treated 63 patients with invasive adenocarcinoma of the rectum by full-thickness local excision. Rigid criteria were employed in patient selection. None of the tumors was pedunculated or in situ carcinoma. Of the 63 lesions, 53 were confined to the bowel wall and constitute the basis for this report. Thirty-five lesions penetrated only the submucosa and 18 invaded the muscularis propria. Twenty-four patients underwent full-dose postoperative radiotherapy with minimal complications. Follow-up ranged from 12 to 130 months, with a median of 44 months. Four tumors recurred locally (8%). Of these, two patients apparently have been salvaged by reexcision. One patient died 32 months after abdominoperineal resection of brain metastases (without local tumor). One patient who did not receive close follow-up died of local recurrence. Seven have died of unrelated causes. The 5-year corrected disease-free survival is 90%. Local excision combined with radiotherapy for selected rectal cancers yields a high rate of cure with minimal morbidity and is now our preferred mode of treatment for all patients whose tumors meet our rigid criteria. PMID- 1598676 TI - Morphologic changes of extrahepatic bile ducts during obstruction and subsequent decompression by endoprosthesis. AB - The morphologic changes of the extrahepatic biliary tract during obstruction and the effects of biliary decompression by means of an endoprosthesis on the bile duct wall were studied by light microscopy and scanning electron microscopy. Common hepatic duct biopsy specimens and bile cultures were obtained during surgery from 30 patients with a distal common bile duct obstruction caused by a tumor. Thirteen patients had obstructed bile ducts of 3 weeks' duration (group A). Seventeen patients had had jaundice for a period of 4 weeks and had subsequently undergone preoperative endoscopic biliary stenting for a period of 4 weeks (group B). Three autopsy specimens from patients without hepatobiliary disease served as controls. The results showed that the initial dilatation and thickening of the obstructed ducts in group A were associated with a mild inflammation, a moderate degree of fibrosis, and local epithelial disintegration. The presence of an endoprosthesis, however (group B), induced severe inflammatory changes with considerable fibrosis and ulcerative lesions, resulting in markedly thickened ducts with lumina approximating the diameter of the stent. Three of 13 (24%) bile cultures in group A were positive and 14 of 17 (82%) in group B were positive. PMID- 1598677 TI - A new surgical technique for voice restoration after laryngopharyngoesophagectomy with a free ileocolic graft: preliminary report. AB - We describe a new one-stage surgical technique for voice restoration combined with reconstruction of the cervical esophagus after laryngopharyngoesophagectomy with a free ileocolic autograft. Reconstruction of the alimentary tract is accomplished with the colonic segment, and the phonatory shunt is fashioned from the terminal ileum. The ileocolic valve, reinforced by "cecal application," functions as an inherent valve that prevents aspiration through the shunt. Six patients underwent reconstruction with this method. There was no graft necrosis, although one venous anastomosis required correction because of kinking. There were two hospital deaths: one patient died of multiple organ failure in the perioperative period and the other died of a recurrence of the disease. The remaining four patients were tolerating a regular diet at discharge from the hospital. Five of the six patients were able to achieve a fair to good voice. PMID- 1598678 TI - Long bone fractures predispose to pulmonary dysfunction in blunt chest trauma despite early operative fixation. AB - Recent reports have demonstrated a decreased incidence of pulmonary complications in patients who have undergone trauma after early operative fixation of long bone fractures. Few studies, however, have specifically examined the effect of associated long bone fractures and their management on pulmonary dysfunction in multiply injured patients with significant blunt chest trauma. We retrospectively reviewed 130 consecutive patients with major blunt chest injury as a component of multisystem trauma. Patients were assessed for overall injury severity and degree of pulmonary dysfunction after being categorized according to associated injury pattern (presence or absence of long bone fracture[s]) and treatment received (early operative fixation at less than 48 hours versus late fixation or nonoperative management). Patients with long bone fractures and concurrent blunt chest trauma had a higher incidence of pulmonary morbidity and death (p less than 0.05) than had patients with similar Injury Severity Scores without long bone fractures. Early operative fixation did not protect against pulmonary dysfunction or death in this group of patients. Despite early operative fixation, long bone fractures predispose patients with concurrent major blunt chest injury to increased pulmonary dysfunction. PMID- 1598679 TI - Interventional embolization with fibrin glue for a large inferior mesenteric caval shunt. AB - We report an unusual case of a large inferior mesenteric-caval shunt in a 25-year old man without cirrhosis with hypoproteinemia and hypochromic anemia. In this large shunt the direct communication was between the inferior mesenteric vein and the internal iliac vein. Hemodynamic change as a result of the shunt was thought to cause his present clinical problems and future portosystemic encephalopathy. Percutaneous transcatheter embolization of the shunt with fibrin glue was performed through the internal iliac vein, and this offered amelioration of hypoproteinemia and reduction of serum ammonia levels without any complications. An interventional radiologic approach instead of surgical ligation should be attempted for portosystemic shunts, and fibrin glue, as well as coils or a detachable balloon, is also valuable as an embolizing material. PMID- 1598680 TI - Variceal hemorrhage associated with portal vein thrombosis: treatment with a unique portal venous stent. AB - A patient with an uncommon cause of portal venous hypertension, pancreatitis, is depicted. The patient had an equally uncommon pattern of symptoms and signs consisting of abdominal pain and lower gastrointestinal hemorrhage caused by colonic varices. A unique treatment, with angiographic placement of an expandable intraluminal stent within the portal vein, was employed to reopen the portal venous system and reduce portal pressure. Relief of bleeding was accomplished and sustained for more than 1 year. PMID- 1598681 TI - Actinomyces as a cause of recurrent perianal fistula in the immunocompromised patient. AB - Actinomycosis is an uncommon bacterial infection that has a characteristic chronic indolent course. Patients with this infection frequently undergo multiple surgical procedures before a correct diagnosis is made. Perianal actinomycosis should be suspected if a nontender perianal mass is found to contain thin purulent material and small yellow particles (sulfur granules). The diagnosis is confirmed by special stains and anaerobic cultures. Recognition of this infection is important because successful treatment requires combined surgical and antibiotic therapy. We report two patients, one with diabetes mellitus and one with human immunodeficiency virus III, who had recurrent perianal abscesses caused by Actinomyces and were treated successfully with surgical drainage and antimicrobial therapy. PMID- 1598682 TI - Double cancer of the gallbladder and common bile duct associated with anomalous junction of pancreaticobiliary ductal system. AB - We report a 64-year-old woman with double cancer of the gallbladder and the common bile duct associated with anomalous junction of the pancreaticobiliary ductal system. Eleven previous cases have been reported to date. From analysis of the 12 cases reviewed, including our patient, double cancer of the gallbladder and the common bile duct accompanied by anomalous junction of the pancreaticobiliary ductal system is characterized by the predominance of well differentiated and superficial cancer. PMID- 1598683 TI - Comparison of HLA class II alleles in Gypsy and Czech populations by DNA typing with oligonucleotide probes. AB - Czechs (CZ) and Gypsies (GY) have lived in the same country for several centuries but seem to have different migratory origins. We have studied 99 CZ and compared them with 34 GY from an isolated group living in Czechoslovakia. DRB1, DRB3, DRB4, DRB5, DQA1, DQB1 and DPB1 alleles were determined by PCR followed by oligonucleotide hybridization. DRB1*0701 was the most frequent DR allele in CZ (af = 36.3%). In GY, after DRB1*0701, DRB1*1404 was the second most frequent allele (af = 29.4%), while in CZ this allele was not found. Both groups differed also in the distribution of DR4 subtypes. In CZ, DRB1*0401 was the most frequent subtype (50.0%) of DR4. In GY, DRB1*0408 was the predominant type (44.4%). A new DQB1 pattern was found in GY, which we have called DQB1*3.4. This allele was similar to DQB1*0301 in codon 26, but in codon 57 it resembled DQB1*0302. All cells having this new allele were also positive for DRB1*0408. Four-locus associations in CZ showed haplotypes similar to those previously found in other Caucasoid populations. In GY we observed more unusual haplotypes, some previously seen in the Orient, possibly reflecting GY ancestry. PMID- 1598684 TI - HLA alleles in the population of Cartagena (Colombia). AB - It is known from historical records that the population of Cartagena (Colombia) is a mixture of caucasoids (Spaniards) and negroids (Africans) that is named mulattos. The present study was carried out to determine the distribution of HLA antigens in this population. A sample of 370 individuals was HLA serologically typed; 91 of them were typed for Complement alleles and 47 were DNA typed using PCR amplification and oligonucleotide probes for the HLA-DQA1 locus. The analysis of the allele and haplotype frequencies obtained, together with the genetic distances calculated with other populations, showed that most of the HLA genes of mulattos are from negroids and caucasoids. The Asian and Amerindian contribution is small, consistent with the historical and socioanthropological documentation. For example, A23, Aw34, Aw36 and Bw45, as well as DQA1*0101, DQA1*0301 and BfF have frequencies similar to that observed in negroids. In contrast, many significant differences were observed when comparing the antigen and allele frequencies of mulattos with that of Asians and Amerindians. Our results add evidence to the notion that the arrival of Spaniards in America 500 years ago established several racial mixtures. The HLA characterization of one of these, mulattos, will allow a better application of the HLA technology in the fields of basic research, organ transplantation and forensic medicine among this population. PMID- 1598685 TI - Isolation and characterization of a genomic HLA-Cw6 clone. PMID- 1598686 TI - HLA-DR antigens and rheumatoid arthritis in black South Africans: a study of ethnic groups. PMID- 1598687 TI - Serological and molecular HLA typing in Italian Behcet's patients: significant association to B51-DR5-DQw3 haplotype. PMID- 1598688 TI - DPB1*WA2 and DPB1*WA3--novel West African HLA DPB1 alleles closely related to the allele DPB1*0101 common in negroid populations. PMID- 1598689 TI - DQB1*WA1--a new DQB1 allele identified in West Africa. PMID- 1598690 TI - A short variant of A9 that is identical to A9V2. PMID- 1598691 TI - A novel method of screening alloantisera in a microcytotoxicity assay using human mutant cells transfected with HLA-class II alleles. PMID- 1598693 TI - [Weight reducing preparations--guiding or misleading?]. PMID- 1598692 TI - Genetics of immune disease. PMID- 1598694 TI - [Obesity and body fat distribution among adult Danes aged 35-65 years. An epidemiological study]. PMID- 1598695 TI - [The effect of an ephedrine/caffeine combination as a supplement to a weight reducing diet. A randomized, placebo-controlled, double-blind trial]. PMID- 1598696 TI - [Psychiatric diseases among the homeless in Funen County]. AB - The purpose of the study was to investigate whether deinstitutionalization of psychiatric patients had produced a clientele of homeless mentally ill people which is not treated. During week 47, 1990, 94 of the 129 residents 73%) in the institutions for homeless people in the County of Funen (population 459,000) were examined for mental illness by a psychiatrist. Diagnoses were made using the ICD 8 classification. Social data were recorded. Eighty-nine per cent were men, 59% were aged 30-49 years, 93% were single, and source of incomes for 80% were public assistance or disability pensions. More than half had been sentenced for crime at least once. The majority suffered from severe psychosocial strain. In 91% a psychiatric diagnosis was established, the most frequent being alcoholism (73%) and personality or character disorder (70%). Psychoses were found in 10 cases or 11%. About 29% required psychiatric treatment. The conclusion was that deinstitutionalization in the County of Funen had not resulted in influx of psychotic persons to institutions for the homeless people. PMID- 1598697 TI - [Homeless psychiatric patients, a study of registration of clients in hostels and foster homes]. AB - In November 1990 a prevalence study and a one month incidence study of previous admissions to psychiatric hospitals or wards were carried out among clients in hostels and care homes in three Danish counties. The study includes Aarhus county, the county of Northern Jutland and the municipality of Copenhagen. Both incidence and prevalence were of approximately the same magnitude in the three counties, between 50% and 75%. When clients who at their latest discharge from a psychiatric hospital or ward were diagnosed alcoholics or drug abusers were excluded the figures were reduced to 25-33%. Eight per cent of the total of 1008 persons investigated (90% males, 10% females) had previously been diagnosed as schizophrenic. Twenty-three per cent of the patients previously admitted to psychiatric hospitals or hostels were admitted to ward or care homes within 24 hours of discharge from hospital and 29% within one month. Among the patients discharged from psychiatric hospitals or wards within two years previous to their present admission to hostels or care homes, 70% were between 25 and 44 years old, 8% younger than 25 years. PMID- 1598698 TI - [Clinical assessment of acute ankle injuries in relation to the need of radiography]. AB - The object of the present investigation was to attempt to assess the value of some selected individual aspect of the clinical examination of patients with acute ankle injuries with tenderness, swelling or haematoma in the neighbourhood of the lateral malleolus. An attempt was made to investigate whether it was possible to differentiate the group of patients in whom radiographic examination of the ankle was necessary and whether this could be done with sufficient certainty on the basis of the clinical parameters examined. The results are presented in the form of calculation of the diagnostic frequencies. Absence of tenderness over the posterolateral edge of the lateral malleolus was found to be the clinical finding which could be employed to exclude fracture with greatest certainty, as the true negative diagnostic frequency was found to be 97.33 (90.70 99.68). This certainty is of the same magnitude as the certainty of previously selected criteria but the examination appears to be simpler and more objective. PMID- 1598699 TI - [Alcoholic ketoacidosis]. AB - Alcoholic ketoacidosis is seen in chronic alcoholics who have been starving for days. This was the case in the present patient who had metabolic acidosis on admission. The differential diagnoses are primarily diabetic ketoacidosis, intoxication (salicylate, methanol, ethylene glycol and fenformin), lactate acidosis, hunger-induced ketoacidosis and uraemia. Treatment should consist of intravenous glucose and correction of the dehydration with isotonic sodium chloride. PMID- 1598700 TI - [Axillary band contractures after axillary lymph node excision]. AB - Three patients are described who developed painful bands across the axilla which severely restricted shoulder abduction after breast surgery and axillary lymph node dissection. They were treated by transection of the bands with excellent results in two of the three patients. The underlying pathology is apparently thrombosis, obstruction and inflammation of lymphatic channels. Treatment should be conservative in most cases, with surgery reserved for patients with intolerable symptoms. PMID- 1598701 TI - [Bacteriological examination of the warm water supply. Suggestions for setting Danish standards]. PMID- 1598702 TI - [Quality assurance and explanation of the concepts]. PMID- 1598704 TI - [Research organization--a professional task]. PMID- 1598703 TI - [Screening for uterine cervix cancer]. PMID- 1598705 TI - [The significance of organized screening for uterine cervix cancer in Denmark during 1968-1987]. AB - The policy concerning organization of screening for cervical cancer has varied in the Danish counties. Organized programmes started in the municipality of Frederiksberg in 1962, in the municipality of Copenhagen and the county of Maribo in 1967, and in the country of Copenhagen in 1968. On the other hand organized screening programmes have never existed in the counties of Vestsjaelland, Viborg, Ringkobing and Ribe. We have used this "natural experiment" to study the influence of organized screening on the incidence and mortality of cervical cancer in Denmark. Women aged 30-59 years during the period 1968-87 are included in the study. The effect of organized screening has been estimated employing multiplicative Poisson models, where age, period, region and organized screening have been considered. Women living in counties where organized screening started three or more years ago have a statistically significantly reduced risk of cervical cancer. The relative risk for the incidence in this group is 0.77 (95% confidence interval 0.69-0.86), and the relative risk for the mortality is 0.75 (95% confidence interval 0.61-0.92). Only a part of the decrease in the incidence and mortality of cervical cancer which can be attributed to the organized screening activity. The additional decrease can be attributed to the considerable unorganized screening activity during the past 20 years, and to changes in exposure to risk factors. PMID- 1598706 TI - [Screening for uterine cervix cancer in Storstrom, Vestsjaelland and Bornholm counties during 1979-1989]. AB - We studied the use of Pap smears in three counties in Denmark, where the screening activity has been organized in different ways. The county of Storstrom had an organized screening programme in 1979-82. Women aged 30-50 years were invited personally, and 91% participated. The same response rate is seen in the county of Bornholm today, where women aged 25-54 years are invited. No invitations are sent in the counties of Storstom and Vestsjaelland today, and only 66%-69% of the 30-50 year old women are screened. The Danish National Board of Health recommends commencement of screening at the age of 23 years. However, 53%-57% of the women aged 15-22 years are screened in Storstrom and Vestsjaelland counties today. The percentages of women screened in the older age groups are, on the other hand, low. Only 10%-17% of women aged 60-75 years were screened in 1985 89. The Danish National Board of Health recommends that women aged 23-75 years should be screened once every third year and that positive, atypical and unqualified smears should be followed-up. The county of Bornholm has an organized screening programme, but 21% of the Pap smears are nevertheless used outside the national recommendations. The county of Vestsjaelland has no organized screening programme and 42% of the Pap smear are used outside the national recommendations. It would be possible to screen a considerably higher percentage of the women aged 23-75 years if the screening activity was well organized. PMID- 1598707 TI - [Status of preventive examinations against uterine cervix cancer in Denmark]. AB - In 1986, The Danish National Board of Health published guidelines for cervical cancer screening. These guidelines recommend organized screening with personal invitations every three years to women in the age group 23-59 years, and in the years to come also invitations to women aged 60-74 years. Five years have now elapsed since publication of these guidelines, and we have therefore studied the present organization of cervical cancer screening in Danish counties. Organized screening programmes are now, medio 1991, running in 11 out of the 16 "counties" (this includes the municipalities of Copenhagen and Frederiksberg). One county follows the national guidelines entirely. Six counties follow these guidelines in general, but they do not invite women over the age of 60 years. In all, 45% of women aged 25-74 years are at present invited for cervical cancer screening in Denmark. Two counties have decided to start organized screening programmes in 1992. PMID- 1598708 TI - [Echocardiography in acute myocardial infarction]. PMID- 1598709 TI - [Early discharge after acute myocardial infarction. Cost-effectiveness of early echocardiographic risk evaluation]. AB - A total of 195 consecutive patients with acute myocardial infarction were examined and risk classified (low or middle/high risk) on the fifth day by two physicians. These two physicians employed two different sets of criteria: conventional clinical examination compared with 2-D echocardiographic assessment of the wall motion of the left ventricle (wall motion index, WMI). Both physicians concluded their examination by determination of a theoretical time for discharge. By design this was on the 5th-7th days for low risk patients by echocardiography, while low risk patients by clinical criteria are normally discharged on the 7th to 8th days. The most sensitive method of identifying the low risk patients was achieved by combining the clinical examination with echocardiographic WMI determination. In this manner, a total of 104 (53%) low risk patients could be identified. A potential saving of 18% of the total duration of hospitalization could be calculated from the two theoretical times of discharge for the total population. All of the patients in this study could be assessed by echocardiography which provided valuable information and thus may be implemented in the routine treatment of acute myocardial infarction. PMID- 1598710 TI - [Relation between 1-year mortality after acute myocardial infarction and left ventricular ejection function estimated by echocardiography]. AB - The pump function of the left ventricle was characterized by means of early echocardiographic determination of the motion of the ventricular walls (wall motion index, WMI) in a consecutive unselected series of 195 patients with acute myocardial infarction. The pump function, WMI, was related to one-year mortality after infarction. The patients were subdivided prospectively into three risk groups (low, middle and high) depending on WMI. One-year mortality in the three groups were 2%, 34% and 37%, respectively (p less than 0.0001). Patients with previous infarcts had significantly lower WMI and greater one-year mortality than patients with first infarct (p less than 0.001 and less than 0.05, respectively). Among patients with first infarct with inferior localization, significantly higher WMI and lower one-year mortality were found than with anterior localization (p less than 0.001 and = 0.15, respectively, (NS)). Women had significantly higher one-year mortality than men (30.2% compared with 16.9% (p less than 0.04)) although this was reflected by a corresponding difference in WMI. Regardless of sex, age, localization of the infarct and signs of residual ischaemia, patients who were allocated to the low risk group solely on the basis of WMI, had particularly good prognoses. Among patients with more extensive myocardial damage, WMI less than or equal to 1.3, other risk factors probably played a greater role. PMID- 1598711 TI - [Acute recurrent chest pain originating in the esophagus. A review]. AB - In half of the patients admitted for observation for acute myocardial infarction, this diagnosis is disproved. Gastro-oesophageal reflux and/or disturbances of oesophageal motility are the cause of the thoracic pain resulting in hospitalization in 16-34% of these patients. In 13-59% of the patients with chronic recurrent thoracic pain without demonstrable ischaemic cardiac disease (IHD), oesophageal disease is, similarly, considered to be the cause of the pain. It is not possible to distinguish whether the pain is caused by oesophageal disease or IHD on the basis of the history, but the differential diagnosis is important as patients with pain on account of oesophageal disease have a good prognosis as regards mortality. The physical and mental conditions of the patients may be improved if the correct diagnosis is established and treatment instituted. Methods of examination to demonstrate oesophageal disease are described. On account of the frequency of the condition and the extent of the methods of examination, a programme of investigation is proposed for patients suspected of having thoracic pain due to oesophageal disease. PMID- 1598712 TI - [Violence towards personnel of emergency departments]. AB - During the period 1.7.1988-31.12.1988, 49 episodes of violence occurred in the Casualty Department of Hvidovre Hospital. This corresponds to one every 3.3 days. In three cases, the violence resulted in injury to the staff treating the patient. The authors found a marked preponderance (82%) of young men in the group of violent patients. Alcohol was a probable potentiating factor for the violence as approximately half of the patients were drunk. The authors did not consider that the waiting time was of any significance. Prophylactic measures are suggested. PMID- 1598713 TI - [Cigarette smoking and time before pregnancy among Danish pharmacy assistants]. AB - The relationship between time to pregnancy and cigarette smoking was studied in a group of 4,924 pharmacy assistants under 40. The information was collected by means of a self administered questionnaire and the response rate was 92%. The data were analysed by a recently developed statistical model for description of time to pregnancy, which provides a more revealing test than the classic contingency table analysis. The study shows that smokers have a median time to pregnancy which is 27% longer than for non smokers. This may partly be due to lifestyle associated with smoking (e.g. alcohol and caffeine intake). Lifestyles such as these have been reported to prolong time to pregnancy. It is shown that time to pregnancy is an easily obtained measurement of fecundity. Only 3.6% of the women were unable to remember their time to pregnancy. The conclusion of the study was that information pertaining to the relationship between fertility and smoking habits/lifestyle should be a part of the instruction for women who wish to become pregnant. PMID- 1598714 TI - [Changed attitude of the Medico-legal Council to ureteral injuries related to hysterectomy]. PMID- 1598715 TI - [Research, sense of proportion and source criticism]. PMID- 1598716 TI - [The role of physical therapy and therapeutic possibilities]. PMID- 1598717 TI - [Use of thermotherapy, ultrasound and laser by practising physiotherapists. Physiotherapists' choice of treatment]. AB - The purpose of this examination was to examine the practising physiotherapist's way of treating patients with nine selected diagnoses (fibrosites, osteoarthritis, rheumatoid arthritis, cervical slipped disc, lumbar slipped disc, generalized lumbar/back pain, generalized bursitis, generalized tendinitis, and sprains). In addition, nine different forms of therapy were examined (hot packs, infra-red light, ice packs, short waves, microwaves, diadynamic current, ultrasound, transcutaneous electric nerve stimulation and laser). All in all, 41 clinics with 2,018 treatment confrontations in the examination period, the last week of March 1990, took part in the survey. The majority of therapists were in possession of short wave, hot packs, ultrasound and laser which are also the four forms of therapy most frequently used for treatment. Compared to a Swedish examination from 1979, there is a doubling in ultrasound treatments from 24% to 48%, while the amount of short wave and microwave treatment remained unchanged. There was a remarkable variation in the physiotherapist's choice of therapy in each different diagnosed case. This can be due to the lack of specification of the diagnosis, so that different symptoms, course and stage of illness changed the treatment pattern elected. PMID- 1598718 TI - [Suicide among psychiatric patients]. AB - Investigation of the development in the incidence of suicide among psychiatric patients is reviewed and it is concluded that the majority of investigations have demonstrated an increasing suicide rate even when the increasing numbers of admissions and discharges are taken into consideration. It is concluded that altered circumstances for psychiatric patients have played a part in relation to the increase in the suicide rate. Investigation of the suicide rates related to diagnoses suggest that manic-depressive patients, alcoholics and schizophrenics have the highest suicide rates. In investigations of patients who died from suicide as compared with patients who did not die from suicide but who were otherwise comparable, it appears that unmarried status, male sex and previous attempted suicide and suicidal thoughts are more frequently correlated with subsequent suicide. Medical audit in connection with suicide among psychiatric patients is discussed as a possible method of improving the training and competence of psychiatric staff in relation to suicidal behaviour. PMID- 1598719 TI - [Non-radioactive in situ hybridization with chromosome-specific probes]. AB - Non-radioactive in situ hybridization (ISH) is a relatively new and sensitive method for analysis of chromosome aberrations. ISH may be performed on metaphase spreads or directly on interphase cells. By means of ISH, the so-called probes are bound to well-defined regions on the chromosomes of a cell. After a visualization process the probes and thus indirectly the chromosome regions may be observed in a microscope. Chromosome-specific probes become bound to chromosomal DNA segments which are specific for certain groups of chromosomes or only for a single chromosome. The chromosome-specific probes may be subdivided into 1) repetitive probes which are bound at or around the centromere, 2) painting probes which are bound to a certain chromosome in its entire extent or to a limited segment of this and 3) locus-specific probes which are bound to a single unique DNA sequence in the genome. ISH with chromosome-specific probes is of great scientific significance for chromosomal localization of genes. It is to be anticipated that this technique may be employed clinically e.g. in prenatal diagnosis and in the diagnosis of cancer and viruses. PMID- 1598720 TI - [Balint's syndrome--visual disorientation]. AB - The three major components of the Balint's syndrome are described: 1) visual disorientation or simultanagnosia, i.e. the inability to perceive the visual field as a whole, 2) ocular apraxia, a deficit of visual scanning and 3) optic ataxia, an impairment of pointing and reaching under visual guidance. Our description of the syndrome is illustrated by three case histories. The complete syndrome is rare, and partial syndromes have been reported more frequently. Sudden and severe hypotension resulting in bilateral borderzone infarction in the occipito-parietal region is reported to be the most frequent cause of complete Balint's syndrome. Lack of awareness of the syndrome may lead to misdiagnosis such as blindness, psychosis, or dementia. PMID- 1598721 TI - [Patients' activity and length of stay after hip arthroplasty with balanced analgesia and early mobilization]. AB - Thirteen consecutive patients were submitted to hip-replacement by Muller's method under epidural analgesia and were treated for postoperative pain with balanced analgesia by means of continuous epidural infusion of a mixture of bupivaine (0.625 mg/ml) and morphine (0.05 mg/ml) 4 ml hourly for 96 hours and supplemented by 600 mg ibuprofen every eight hour orally. The analgesic treatment was combined with intensive mobilization regime and altered postoperative care as regards early normalization of daily activities and reduced duration of hospitalization. The patients were found to be effectively relieved of pain during rest and also during mobilization and, together with suitable care and rehabilitation, this had the result that more than half of the patients were mobilized from bed for more than eight hours from the second postoperative day and that all of the patients were able to carry out ordinary everyday functions after the fourth postoperative day, with the assistance of the aids which the hip regimen required. Eleven of the patients were ready for discharge on the sixth postoperative day while two patients were not discharged until the eighth and ninth postoperative days on account of slight surgical complications. All of the patients were discharged to their homes and to outpatient rehabilitation for three weeks. Compared with the usual duration of hospitalization of approximately 13 days in corresponding patients, this pilot investigation appears to show that the analgesic regime employed was extremely effective but that traditional attitudes and routines in the postoperative care and mobilization must be revised if this is to be utilized for more rapid restitution and reduced duration of hospitalization. PMID- 1598722 TI - [Dentobronchial syndrome. Can persistent productive cough be caused by parodontitis? A questionnaire study]. AB - In order to investigate the statistical relationship between periodontal disease, symptomless sinuitis and chronic cough an epidemiological survey was performed by questionnaire among 186 patients (age 30-60) suffering from serious periodontal disease. 58% responded. Persistent cough with expectoration was reported only by patients suffering from periodontal disease in the upper molars. The relative risk was significant (p less than 0.01). The prevalence in this group was 28% compared to a 12% prevalence of chronic bronchitis in the normal population. Ten of the patients with persistent cough reported amelioration of symptoms shortly after the dental treatment. This includes eight smokers who continued smoking. The dentists confirmed that the patients in question had very serious periodontal disease. Further investigations including clinical control and X-ray of the teeth and sinuses are recommended. PMID- 1598723 TI - [The venereological profile in Godthab District Venereal Clinic, Nuuk, Gronland. A 3-month study in 1991]. AB - A total of 803 patients participated in a consecutive review of the disease pattern concerning venereal diseases. The investigation took place in the Clinic for Venereal Diseases in Nuuk/Godthab during a period of three months. Less than half of the contacts were on account of symptoms of genital infection. One fifth of the patients had been summoned for partner control. A corresponding proportion felt well and had not been exposed to any known risk of infection. Chlamydia trachomatis was demonstrated in 19% and gonorrhoea in 10%. Among the asymptomatic persons, 16% were found to be Chlamydia positive and 0.6% gonococcal positive. Syphilis was demonstrated in one man and one woman. One man was known to be HIV positive and two contacts of this patient were found to be negative but seroconversion occurred subsequently in both cases. Vaginitis and bacterial vaginosis were found in 38% of the women. In over one third (39%), no clinical or microbiological evidence of genital infection was found. Early diagnosis, treatment, information and tracing of contacts are still the cardinal principles in the combat of venereal diseases in Greenland. PMID- 1598724 TI - Immune modulating effects of low doses of cyclophosphamide and keyhole limpet hemocyanin on peripheral blood immune parameters in patients with metastatic renal cell carcinoma. AB - Assessing the peripheral blood immune status, we had found evidence of immunosuppression in metastatic renal cell carcinoma. Since immunosuppression might interfere with the outcome of immunotherapy, it was submitted to further investigation. Immunosuppression can be mediated by T suppressor cells, which for their part are inhibited by low-dose cyclophosphamide (Cy). We tested whether the immunomodulating effects of the biological response modifier keyhole limpet hemocyanin (KLH) on cellular and humoral immune parameters would be intensified by low-dose Cy. 10 patients were given 300 mg/m2 Cy i.v. 3 days before application of 1 mg KLH i.m. up to 8 times in 4-weekly intervals. Immune parameters were assayed twice pre-therapeutically, and prior to and 1 day and 1 week after each KLH injection. In contrast to the results obtained with KLH-mono application, lymphocyte subsets-with the exception of T4 cell counts and the T4/T8 ratio-remained stable during the first 4 months of observation. There were increases in immunoglobulins and in the immunoactivation markers tumor necrosis factor, neopterin and beta 2-microglobulin. The tendencies found here differed from those found in a previous study on patients who were given KLH alone, and were similar to those found in patients with nonmetastatic disease who received KLH alone. However, the increases of the activation markers during KLH+Cy application were at best half as much as in patients with nonmetastatic disease. In conclusion, immunosuppression was influenced, but not counterbalanced by low dose Cy. Most probably other mediators of immunosuppression than T suppressor cells, for example prostaglandin E2, must be considered as well.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598725 TI - Cavitary pulmonary metastases in transitional cell carcinoma of the urinary bladder. AB - About 4% of metastases to the lung eventually evolve into cavitary lesions. The origin of these lesions are squamous cell carcinomas in 69% of cases and adenocarcinomas in the rest. Lung metastases develop in 20% of patients with transitional cell carcinomas of the urinary bladder (TCB), usually as multiple nodules. The cavitation of these metastases is an unusual finding, and a review of the literature has revealed only 7 cases of cavitary metastatic lesions from TCB. We add 2 further cases with cavitary metastases and study their clinical and radiographic features, in comparison with those previously described in the literature. PMID- 1598726 TI - Squamous cell carcinoma of the male urethra mimicking a paravertebral abscess. AB - In the context of a misleading diagnosis of paraurethral abscess, we report a case of unrecognized metastatic squamous cell carcinoma of the male urethra that mimicked a picture of paravertebral abscess with accompanying massive caval vein thrombosis. Fine needle aspiration cytology of both paravertebral abscess and urethral nodule allowed the diagnosis. This report calls the attention of clinicians to think of a malignant process in case of a paravertebral abscess. Fine needle aspiration cytology once more proves a useful tool in the diagnosis of unsuspected malignancies. PMID- 1598727 TI - Extensive retroperitoneal hematoma following extracorporeal shock wave lithotripsy with second generation lithotriptor. AB - A patient with extensive retroperitoneal hematoma after extracorporeal shock wave lithotripsy (ESWL) with a second generation lithotriptor is presented. Apart from bilateral ESWL for renal calculi in 1987 the patient had a negative history of previous renal disease or risk factors associated with hemorrhage following ESWL. Ultimately surgery was required to control bleeding from a capsular artery. The kidney could be salvaged. The shock wave characteristics of the different lithotriptors are discussed and the cases of subcapsular hemorrhage after ESWL reviewed. PMID- 1598728 TI - Giant vesical calculus presenting as vesicocutaneous fistula. PMID- 1598729 TI - Giant calculus in anterior urethral diverticulum. AB - The case of probably the largest stone in a giant anterior urethral diverticulum presenting with septicemia and renal failure is reported. Stage surgical reconstruction had an excellent result. PMID- 1598730 TI - Carcinogenesis associated with dimethyl sulfoxide. PMID- 1598731 TI - Peptidergic innervation of the normal and obstructed human pyeloureteral junctions. AB - The neuropeptidergic innervation of the normal and obstructed human pyeloureteral junction was investigated using immunohistochemical techniques. A dense innervation of neuropeptide Y (NPY) and vasoactive intestinal polypeptide (VIP) in the intrinsic obstruction type was demonstrated. NPY and VIP formed networks in the muscular layer. NPY was also found in perivascular plexuses and VIP adjacent to the epithelium. Calcitonin gene-related peptide, galanin and substance P nerves were also seen in the muscular layer, although sparsely. It is proposed that NPY and VIP have a role in the pathophysiology of the intrinsic obstruction type of the human pyeloureteral junction. The innervation pattern of the junction with the external type of obstruction was similar to that of the normal pyeloureteral junction. PMID- 1598732 TI - Relaxant effect of thiphenamil HCl on upper urinary tract frequency of contraction of healthy asymptomatic volunteers. AB - The pharmacologic effect of thiphenamil HCl on the upper urinary tract as a relaxant of renal pelvic contractions was studied. A total of 17 subjects with no known upper urinary tract abnormalities were scanned. A Diasonics ultrasound scanner at 3.5 MHz was used to visualize the kidney and renal pelvis with the subject in the supine position. Control recordings of renal pelvic and calyceal contractility were made on videotape for approximately 30 min. The subject was then given a single dose of 400 mg thiphenamil HCl and visualization of contractility continued for approximately 60-90 min. Criteria for the evaluation of the data were the mean frequency of pelvic contraction cross-section of the pelvis, and velocity and direction contraction. Ultrasonic images were filtered by a video filtering process and averaged using the digital conversion and summation in real time. The results show that under control conditions renal pelvic contractions are at a frequency of 2 +/- 1.8 min-1. Contractions are initiated with the intrarenal pelvis and continue towards the ureter at a rate of 1.3 +/- 0.8 cm/s. Following thiphenamil HCl, there is a significant reduction in pelvic contraction frequency, 0.6 +/- 0.6 min-1, and the opposing walls of the renal pelvis do not completely close in the formation of a bolus. The results obtained from this study demonstrate that thiphenamil suppresses upper urinary tract contractility. As a consequence of this observation, it is postulated that this agent may be of use in the acute relaxation of the upper urinary tract for renal colic and stone management. PMID- 1598733 TI - Importance of the active component of the detrusor muscle in bladder compliance. AB - An appropriate experimental study was designed and carried out in mongrel dogs, in order to evaluate the active muscle and cholinergic participation on bladder compliance. The filling bladder pressure was measured at 100 ml of bladder volume, in 50 dogs distributed into five groups of 10 dogs each: (1) control group, (2) group which received atropine (cholinergic antagonist), (3) group which received verapamil (extracellular Ca2+ blocker), (4) group which received nitroprusside (intracellular Ca2+ antagonist), and (5) group which received EGTA (Ca(2+)-chelating agent). Furthermore, the following was demonstrated. (1) The greatest decrease of the bladder filling pressure was observed in the group which was treated with EGTA. (2) A significant decrease of the bladder filling pressure was also seen in the group which was given nitroprusside. (3) The decrease of bladder filling pressure in the verapamil group tended towards statistical significance. (4) There was no decrease in the atropine group. Thus, it was concluded that the active muscle component has an important role in the bladder compliance (through the intracellular calcium fraction), and the cholinergic component does not participate in the bladder compliance. PMID- 1598734 TI - Pharmacologic treatment of detrusor incontinence with thiphenamil HCl. AB - A controlled double-blind crossover study is reported in which quantitative urodynamic data and qualitative information are combined to evaluate the treatment of detrusor incontinence using thiphenamil HCl in patients with detrusor instability. Patients placed on the treatment protocol were randomized to placebo or thiphenamil 400 mg q.i.d. Two weeks of thiphenamil HCl or placebo administration were followed by 1 week of washout followed by a cross-over to an additional 2 weeks of placebo or thiphenamil HCl administration. Of the 23 patients 7 dropped out at various stages of the study. The mean age of patients studied was 44 +/- 14 years old. Throughout the study, patients were asked to complete a formalized diary card of the amount and time of voiding and the incidence of incontinence. Three urodynamics studies were done in the following sequence: pretreatment, postwashout, and posttreatment. Parameters of bladder capacity, sensations, stability and pressure/flow were obtained. In addition, resting urethral closure pressures were recorded. The results show that the frequency of incontinence, which was based on the patients' responses, decreased significantly (0.01 less than p less than 0.025). There was an insignificant decrease in the number of voidings and increase in the amount voided each time. Patients on thiphenamil reported that their pads were significantly drier from baseline (p = 0.01). In response to questions comparing problems caused by urine loss during baseline and thiphenamil treatment, analysis shows a significant decrease of problems due to loss of urine (p = 0.01) when the patient was taking the drug compared to the placebo.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598735 TI - Perineal pudendal neurotomy versus selective neurotomy of the S2 somatic contribution to the pudendal nerve. Effects on sacral-root-stimulated bladder and urethral responses in the dog. AB - In 10 dogs that underwent bilateral electrode implantation on the S2 ventral root, 5 then underwent a bilateral total perineal neurotomy of the pudendal nerve (group A) at 3 months and 5 bilateral division of the S2 somatic contribution to the pudendal nerve (group B). The effects of these 2 types of neurotomy on the bladder and urethral responses to electrostimulation were compared after another 3 months. In group A, the proximal and mid-urethral responses decreased significantly [69.1% (p = 0.004) and 79.6% (p = 0.002), respectively]. A decrease in bladder response [26% (p = 0.089)], although not significant, was also found. In group B, the decrease in the proximal urethral response was significant [67.8% (p = 0.012)]; the mid-urethral response (56.8%) was not statistically significant (p = 0.134). The bladder response decreased by 73.6% (p = 0.034). Thus, although pudendal neurotomy can be effective in reducing the outlet resistance, the pudendal nerve may have an important role in the regulation of micturition in the dog. Preoperative testing of the effect of a pudendal neurotomy by temporary nerve blocks is warranted to avoid undesirable side effects such as a decrease in bladder excitability. PMID- 1598736 TI - Increase in venous outflow from the corpora cavernosa during mild erection in dogs. AB - The venous outlet of the corpus cavernosum is generally believed to be obstructed during erection. Some researchers, however, have demonstrated an increased venous outflow during erection. To elucidate this discrepancy, we carried out a pressure flow study using a perfusion model of the penile deep artery in dogs. Various states of the corpus cavernosum, which were different in cavernous pressure, were induced by a delicate control of electrostimulation to the cavernous nerve. Inflow rate into the corpus cavernosum, inflow resistance and outflow resistance were simultaneously evaluated. The inflow rate in mild erection was higher than in the flaccid state, and the outflow rate was estimated to be also higher than in the flaccid state. A probable reason for the increased outflow rate was that the arterial resistance decreased remarkably, while the venous resistance only slightly increased. In full erection, both the inflow and outflow rates were lower than in the flaccid state because of a great venous resistance. Histological observation of the canine penis indicated that compression of draining veins passing through the tunica albuginea was weak in mild erection, while intense in full erection. It was proposed that in mild erection, the effect of venous occlusion was slight though that of arterial dilation was noticeable, resulting in an increase in the venous outflow. PMID- 1598737 TI - Mechanism preventing backflow from the canine corpora cavernosa to arteries in the rigid phase of penile erection. AB - The present study was performed in dogs to determine the site preventing the backflow from the corpus cavernosum to the arterial vessels when the corporeal pressure rises more than the systemic pressure (rigid phase). We confirmed a great gradient (325 +/- 81 mm Hg, mean +/- SD) between the corporeal pressure and the deep arterial pressure; the latter was measured at the distal point over the tunica albuginea, namely within the corpus cavernosum. This finding indicated that the mechanism preventing the arterial backflow existed within the corpus cavernosum. This assumption was supported by our light-microscopic findings that the helicine arteries were closed in the rigid phase, whereas they were dilated when the corporeal pressure was lower than the systemic pressure (tumescence/full erection phase). The results suggest that the helicine arteries play an essential role in the prevention of the arterial backflow in the rigid phase. PMID- 1598738 TI - Primary extracorporeal shock wave lithotripsy of staghorn renal calculi. AB - 186 patients with partial and 55 patients with complete renal staghorn calculi were treated with primary extracorporeal shock wave lithotripsy (ESWL) at the Department of Urology, University of Wurzburg Medical School. Partial staghorn calculi required an average of 1.4, complete staghorn calculi an average of 2.2 treatment sessions using the Dornier HM 3 lithotriptor. 55% of all patients and 46% of the patients with complete staghorn calculi were rendered stone-free within 1 year after ESWL. Pretreatment urinary tract infections present in 50.6% of all patients could be reduced to 22.5% 1 year after ESWL. The most frequent complications after ESWL were ureteral obstruction caused by 'steinstrasse' (41.4%), fever (38.4%), and renal colics (29.4%). Severe complications needing open operative procedures or blood transfusions did not occur. 50% of all patients underwent auxiliary procedures (e.g. insertion of indwelling ureteral stents: 25.3%, percutaneous nephrostomy: 20.3%, percutaneous nephrolithotripsy: 2.9%). Pretreatment insertion of an indwelling ureteral stent was found to reduce posttreatment complications as well as the need for percutaneous nephrostomy only in patients with partial staghorn calculi. The data presented in this study demonstrate that primary ESWL therapy can be safely and successfully performed in the majority of patients with renal staghorn calculi. In patients requiring complete removal of all stone fragments, a percutaneous lithotripsy can be performed following ESWL. PMID- 1598739 TI - Long-term experience with transurethral rigid ureteroscopy as a complementary method to extracorporeal shockwave lithotripsy. AB - Between May 1985 and September 1990, 291 ureteroscopies were performed either for primary or secondary stone therapy or for diagnostic purposes. Rigid ureteroscopes (12.5 or 9.5 French) were used without dilation of the ureteral orifice. 83% of the stones could be removed either by direct extraction or electrohydraulic or ultrasound lithotripsy. The highest failure rates (25.6%) occurred in stones located in the upper ureter, the lowest failure rate (9.6%) resulted from treatment of lower ureteral stones. 3.4% complications were observed such as perforation, leakage, stenosis and septicemia. After an average follow-up of 4.5 months, 1 in 70 patients revealed an ureteropelvic stricture which was treated with open surgery. The ureterorenoscopy represents an effective and low-risk primary and secondary method for treatment of ureteral stones in stone centers using extracorporeal lithotriptors which are exclusively equipped with ultrasound detection devices. PMID- 1598740 TI - Imaging of infantile polycystic kidney disease with some rare association. AB - Seventeen patients, age 1 day to 6 years with infantile polycystic kidney disease were evaluated with ultrasound and other imaging techniques. Most patients showed bilaterally enlarged kidneys with hyperechoic renal parenchyma, which had poor differentiation in outlines as well as between renal sinus, cortex and medulla. Cysts of various sizes were also identified in the kidneys. However, a third of these cases showed well-defined renal outlines, normal echogenic cortical rim, whilst dilated renal collecting systems were seen in another third of the cases. Twelve cases showed hepatomegaly. Few rare findings such as liver cysts, associated Meckel syndrome, renal stone, bilateral vesicoureteric reflux and renal calcification were also noted. This study confirms the diagnostic value of sonography and intravenous pyelography examination. However, the noninvasiveness and the opportunity for repeat examination in antenatal and postnatal life makes sonography the ideal investigative modality. PMID- 1598741 TI - ABO and rhesus blood groups as prognostic factors in transitional cell carcinomas of the upper urinary tract. AB - In a study of 290 patients with transitional cell carcinoma of the upper urinary tract an excess of blood group A was found. Comparisons between blood group A versus O and rhesus-positive versus rhesus-negative in relation to tumor stages or grades of dysplasia showed no significant differences neither at presentation nor in actuarial survival rates. It is concluded that the blood group systems ABO and rhesus have no prognostic value in urothelial tumors of the upper urinary tract. PMID- 1598742 TI - Leiomyoma of the urinary bladder floor: diagnosis by transvaginal ultrasound. AB - We studied a case of leiomyoma of the bladder floor in a woman with excretion urography, voiding cystourethrography, abdominal echography, computed tomography scan, and transvaginal echography. This last technique gave us the most accurate information about localization of the mass and its relation to adjacent organs. With these data we were able to indicate the most suitable surgical access. We think that this new application of the transvaginal echography should be included in the study of bladder flow masses in the female. PMID- 1598743 TI - Renal cell carcinoma in uremic acquired renal cystic disease: incidence, detection, and management. AB - Patients with end-stage kidney disease, particularly those treated with dialysis, have an increased risk of renal cell carcinoma. Renal cell carcinoma may also develop in the native kidneys of renal transplant recipients with good graft function many years after transplantation. Recent studies suggest that the incidence of renal carcinoma among dialysis patients is 3-6 times greater than in the general population. However, annual imaging of the native kidneys of all dialysis patients is not justified because it has not been shown to have a significant effect on patient outcome. Screening may, however, be useful in selected patients with good general medical conditions and who have known risk factors for renal carcinoma. PMID- 1598744 TI - Arteriovenous fistulas in renal transplants: color Doppler ultrasound observations. AB - One hundred twenty-six new renal transplants were scanned regularly with color Doppler ultrasound (CDU). In 22 (17.5%) of the grafts there was evidence of postbiopsy arteriovenous (AV) fistula during the first 6 months postoperatively. In 14 cases the fistula closed spontaneously. In the remaining eight, the fistula was still present up to 24 months later (four cases) or until the graft failed (four cases). Additionally, 163 established grafts were scanned for evidence of vascular abnormality. AV fistulas were observed in 15 grafts (8%). Circulatory complications of fistulas observed include vascular steal and a possible association with graft vein and artery stenosis. PMID- 1598745 TI - Hyperdense renal cyst due to prolonged retention of iodinated contrast material: case report. AB - A case of a hyperdense renal cortical cyst resulting from cyst puncture and opacification 28 months previously is reported. Prolonged retention of water soluble iodinated contrast material is an unusual cause of a hyperdense renal cyst, which has not previously been described. The findings on serial computed tomography (CT) and chemical analysis are presented and discussed. PMID- 1598746 TI - Sonographic detection of renal changes in pseudoxanthoma elasticum. AB - Pseudoxanthoma elasticum (PXE) is a rare hereditary disease whose basic abnormality is degeneration of elastic tissue, with calcification of the tonaca media of the arteries, and typical yellowish papules of the skin. We report the sonographic findings observed in a young patient with PXE at the level of the kidneys: fine hyperechogenic spots suggesting small calcifications were diffuse at the corticomedullary junction; however, normal waveforms were obtained at the level of intraparenchymal renal vessels. The presence of this structural pattern in a young patient with dermatologic abnormalities should lead to the consideration of PXE in the differential diagnosis list. PMID- 1598747 TI - Intraluminal renal metastasis from colon cancer simulating a fungus ball. AB - Reports of renal metastasis from colon cancer are unusual, and none have described intraluminal renal metastasis. We describe a patient with a radiolucent filling defect in the renal pelvis that was discovered by percutaneous nephrostomy during prophylactic nephrostomy tube change. Imaging and laboratory results indicated a fungus ball, but pathologic diagnosis of the percutaneously extracted mass was metastatic colonic adenocarcinoma. PMID- 1598748 TI - Aldosteronoma coexisting with renal artery stenosis in secondary hypertension. AB - A case of secondary hypertension due to an aldosteronoma coexisting with renal artery stenosis is reported. Tumor resection resulted in an immediate but short lived clinical relief. Follow-up aortography revealed progressive arterial stenosis and infrarenal aortic occlusion. Differential renal venous renin and renal scintigraphy suggested renovascular hypertension. It is necessary to search for a second curable lesion if hypertension remains uncontrollable after surgical correction of an apparent cause. PMID- 1598749 TI - Ureteric obstruction by the right testicular vein: CT diagnosis. AB - The close relationship of the ureter and gonadal blood vessels is often clearly demonstrated by computed tomography (CT). A case of ureteral obstruction in a man possibly caused by the crossing testicular vein is presented. Unlike the ovarian vein syndrome in women, which is often related to pregnancy and/or venous thrombosis, no predisposing factors were found. PMID- 1598750 TI - Congenital anomalies of the inferior vena cava: embryogenesis and MR features. AB - This article describes the MR appearances of the six most common congenital anomalies of the inferior vena cava. As a basis for understanding those anomalies, it describes the embryology of the inferior vena cava, based on an actual study of embryos and fetuses. The article takes a fresh look at the original research in this area, discusses the possible embryogenesis of the relevant anomalies, and describes different opinions on that subject, where different opinions exist. PMID- 1598751 TI - Reversed contrast-urine levels in urinary bladder: CT findings. AB - Contrast-urine levels are routinely seen in contrast-enhanced computed tomography (CT) of the pelvis with contrast-opacified urine in the bottom and unopacified urine in the top. We encountered four cases in which contrast-urine levels were reversed. The reversal of the contrast-urine level was probably caused by high specific gravity of the preexisting urine in the bladder due to infectious debris or mucous threads in the urine. PMID- 1598752 TI - Serum fructosamine in canine diabetes mellitus. An initial study. AB - This study reports on a spectrophotometric assay for the determination of serum fructosamine concentration. The assay was evaluated for use in canine serum samples by assessment of the precision, accuracy, detectability and stability of serum fructosamine during storage. To evaluate the diagnostic usefulness of the assay, both the effect of acute changes in blood glucose on serum fructosamine concentration and the serum fructosamine concentration in canine diabetes mellitus and other canine diseases were studied. The main conclusions can be summarized as follows: Determination of canine serum fructosamines may be achieved by a precise and accurate assay with a detection limit well below the serum fructosamine concentration normally found in canine sera. Storage for 5 days at +4 degrees C or +25 degrees C, or for 28 days at -20 degrees C caused no significant change in serum fructosamine concentration. The concentration is not affected by acute changes in blood glucose. In diabetic dogs, serum fructosamine concentration is significantly greater than in dogs with other diseases. PMID- 1598754 TI - Cardiomyopathy in cattle induced by residues of the coccidiostat maduramicin in poultry litter given as a feedstuff. AB - An experimental feeding trial was conducted in order to substantiate an hypothesis on the aetiology of a previously unrecorded cardiomyopathic syndrome in beef cattle in Israel. It was believed that residues of the ionophore maduramicin (Cygro; American Cyanamid) in poultry litter fed to cattle, after the maduramicin had been incorporated into broiler feed as a coccidiostat, were the cause of the cardiomyopathy. Three groups of 5 heifers were fed for several weeks (1) poultry litter from a field case, containing 4.8 ppm maduramicin; (2) poultry litter to which maduramicin was added to give a concentration of 12 ppm; (3) poultry litter with no maduramicin (control). Clinical, biochemical, necropsy and histopathological findings showed that maduramicin residues are cardiotoxic, even at the lower level of maduramicin fed, which is commonly encountered in poultry litter in Israel. PMID- 1598755 TI - Influence of indomethacin on endotoxin-induced changes in gastrointestinal myoelectrical activity and some haematological and clinical parameters in the conscious piglet. AB - The effect of indomethacin, administered intravenously at 5 mg/kg, on the changes in gastrointestinal myoelectrical activity, rectal body temperature, clinical appearance and some haematological parameters induced by intravenous bolus injection of endotoxin, at 10 micrograms/kg, was examined in conscious piglets with electrodes implanted in the antrum pylori, duodenum, jejunum and ileum. Indomethacin inhibited the endotoxin-induced febrile response and the accompanying clinical signs. However, it was without influence on the induced leukopenia and shift to the left. Indomethacin both delayed the onset of and shortened the endotoxin-induced increase in the duration of the antral inhibitory phase and the duodenal phase I activity. It therefore appears that prostanoids are probably not the main factors involved in the endotoxin-induced haematological and gastrointestinal myoelectrical activity changes in the piglet. PMID- 1598757 TI - [Studies on the beta-D-fucosidase from Aspergillus phoenicis]. AB - Although beta-D-fucosidase (beta-D-fucoside fucohydrolase, EC 3.2.1.38) has been isolated from various sources, the identity of this enzyme is still not settled. We have purified a specific beta-D-fucosidase in electrophoretically homogeneous form crude extracts of Aspergillus phoenicis by polyethyleneglycol 6000-phosphate buffer aqueous two-phase separation, and successive chromatography on DEAE Sephadex A-50, hydroxyapatite and Sephadex G-100 columns. The molecular weight of the enzyme was estimated to be 57000 by SDS-polyacrylamide gel electrophoresis and 50000 to 60000 by gel filtration on Sephadex G-100. The enzyme showed optimum coside were 2.4mmol/L, and 1.28 mumol min-1 the pH range 5.5-6.5 and below 35 degrees C. The Km and the Vmax values for pNP-beta-D-fucoside were 2.4mmol/L, and 1.28 mumol.min-1.mg-1 respectively. The enzyme was strongly inhibited by sulfhydryl group reagents, PCMB-NEM and iodoacetate. It was also inhibited by EDC, DEP and NBS. Thus, -SH, -COOH groups, histidyl and tryptophyl residues were essential for enzyme activity. The purified beta-D-fucosidase showed high specificity toward p-nitrophenyl beta-D-fucoside. The enzyme was inhibited by D fucose and D-fucono-gamma-lactone, but not by D-galactose, D-galactono-gamma lactone, D-glucose or D-glucono-gamma-lactone; the latter compounds are specific inhibitors of beta-D-galactosidase and beta-D-glucosidase respectively. Thus, this enzyme is the most strictly specific beta-D-fucosidase when compared with those previously reported. PMID- 1598758 TI - [Isolation and identification of Leclercia adecarboxylate in clinical isolates in China]. AB - 1987, 3 strains of gram-negative straight rods were examined from 3 cases of patients with diarrhea. It's producing yellow pigment, fermentative metabolism of carbohydrates, oxidase test negative and motility with the help of peritrichous flagella. Through systematic biochemical identification, calculation of G+C mol% and homology of DNA/DNA, the species of Leclercia adecarboxylate are identified. While the susceptibility to certain antibiotics and the pathogenicity for white mice are tested, and relation of these microorganisms to clinical diarrhea is discussed. PMID- 1598756 TI - Permeability of the endothelium and partitioning of the pulmonary blood flow resistance in isolated perfused pig lungs: effects of breed and age. AB - The right and left lungs of 5 healthy Minipigs and of 13 healthy Landrace piglets were isolated, perfused at constant pressure and maintained in an isogravimetric state under zone III conditions (pulmonary venous pressure greater than alveolar pressure). By applying the double, arterial and venous, occlusion technique, the total blood flow resistance (R) was partitioned into four components: arterial (Ra), pre- (Ra') and post-capillary (Rv') and venous (Rv). The capillary filtration coefficient (Kf,c) was evaluated by measuring the weight gained by the lungs when the arterial and venous pressures were suddenly increased. In the youngest Landrace piglets (5 weeks old), there was an uncontrolled vasoconstriction which sometimes prevented perfusion of the lungs and induced a large increase in Rt. These high values of Rt were decreased by tolazoline administration. The values of Rt recorded in older pigs (12-13 weeks old) were lower in Minipigs (33.66 +/- 3.77 cmH2O min L-1 per 100 g of lungs; n = 5) than in Landrace piglets (55.20 +/- 6.18 cmH2O min L-1 per 100 g; n = 5). This breed difference was due to the differences in Ra' and Rv'. The mean values of Kf,c were 0.193 +/- 0.015 and 0.202 +/- 0.029 ml min (cmH2O)-1 per 100 g of the lungs in Minipigs and Landrace piglets respectively. All these parameters were stable for the 3 hours following the equilibrium period. It was concluded that: (1) There is an age-related maturation of the control of the vasomotor tone in porcine lungs. (2) Pulmonary microvascular haemodynamics are influenced by the breed of the pigs. (3) There was no difference in the Kf,c values between both the breeds. (4) A comparison of the values reported for dogs and rabbits with our data shows that the pre- and post-capillary resistances and, to a lesser extent, the arterial and venous resistances are relatively high in pigs. PMID- 1598760 TI - [Screening of strain producing extracellular penicillin acylase]. AB - Ninety-eight strains having extracellular penicillin acylase activity were derived from soil samples by colour-developing method. 10 strains of them possess higher activity of penicillin acylase. All of those are found to be Bacillus megaterium. The optimum condition of enzyme production was investigated with the strain No. 46 which is from No. 247 by single colony isolation. The productivity of penicillin acylase in the optimum condition have been enhanced 2.5 times more than that in the screening condition. The mutant strain, Bacillus megaterium UL 81, which penicillin acylase activity reached the level of 723u/100ml of broth was obtained from No. 46 by treatment with physical and chemical factors. The penicillin acylase activity of UL-81 can reach 820u/100 ml in 500L fermentor. The mutant strain differed from parent strain in the morphology of colony, the size of cells, the effect of concentration and the addition time of phenylacetic acid on the production of penicillin acylase. PMID- 1598759 TI - [The characterization of mutant No. 68 from midecamycin producing strain S. mycarofaciens 1748]. AB - A stable mutant No. 68 was obtained by treatment of S. mycarofaciens 1748 spores at high temperature. The electromicroscopic examination has shown that the mutant No. 68 and parent strain 1748 both have the spore chains of the spiratype. The spores of both strain are cylindrical in shape. The only difference is that the spores of the mutant No. 68 are of smooth surface, but the 1748 are of thorny. The physiological characteristics of both strains are also very similar with slight differences in utilization of few carbon sources and in cultural characters in few medium. Feeding experiment has shown that the mutant No. 68 was blocked in the formation of the macrolide lactone in the midecamycin biosynthetic pathway. This suggested that the mutant No. 68 might be a polyketide synthase genes deficient mutant. The ability of the mutant No. 68 to convert spiramycin into 4"-propionylspiramycin indicated that the mutant No. 68 contained the midecamycin 4"-propionyltransferase and could be used for microbial bioconversion of spiramycin into 4"-propionylspiramycin. PMID- 1598762 TI - [Sequence effects in absolute judgment? Critical comments on the method]. AB - Several methods for demonstrating sequential effects in psychophysical judgments are discussed. None of them is free of problems. Simple simulations show that pseudosequential effects occur whenever some subjects judge the stimuli higher or lower than they should. Such effects may also be produced by response drifts during the course of an experiment. Breaks in the psychophysical function might be another source of pseudosequential effects. Contrary to a wide-spread opinion, it still remains to be shown that genuine sequence effects really exist. PMID- 1598761 TI - [Discrimination learning of rotated faces: a Markov analysis of coding and association processes]. AB - 30 subjects participated in a discrimination experiment learning face-letter associations under four rotation conditions (45 degrees, 90 degrees, 135 degrees, 180 degrees). Under each condition two thirds of the faces were presented twice, upright and rotated away from the vertical; the remaining faces were presented once, upright or rotated. Learning is described by a joint Markov model: For faces that are presented twice it assumes a separate association and encoding process (two-stage-model), for faces that are presented once it assumes an association process (all-or-none-model). The Markov model fits the data for all four rotation conditions. The angle of rotation does not affect learning for faces that are presented once. For faces that are presented twice it influences both the association and the encoding process. For the angles employed, the effect of rotation can be approximated linearly. The results suggest that the encoding of a rotated face differs increasingly from an upright face as a function of these angles of rotation. This confirms analogous conclusions from mental rotation experiments. PMID- 1598763 TI - [Measuring mental performance: an old idea and a new approach]. AB - First results are reported from the attempt to make mental performance measurable in terms of elementary thought processes. The formation of order in thought is seen as a unit with which mental performance can be measured. The formation of order is described by complexity-reducing structuring. A measurement process for elementary problem-solving demands based on the symbol-distance effect was also developed. From the comparison with the solution of complex problems, it was shown that those test subjects who attain the best solutions to more complex demands are also those who have the most parsimonious cognitive structures in problem solving. Complexity reduction is measured by the performance of the alpha band in EEG mapping. With the use of a more parsimonious cognitive structure, higher performance is measured in comparison with the use of complexity-intensive cognitive structure. PMID- 1598753 TI - Eosinophils: a review. AB - The eosinophil was discovered by Jones in 1846 (Dessein and David, 1982) but its proclivity to stain with aniline dyes was first described by Paul Ehrlich in 1879 (Hirsch and Hirsch, 1980). Recognized and named for this quality, eosinophils possess an abundance of highly basic proteins within their granules which confer their affinity for acidic dyes (Gleich and Loegering, 1984). Eosinophils are traditionally viewed as killer-effector cells in parasitic infestations and as modulators of Type I hypersensitivity reactions (Butterworth and David, 1981; Kay, 1985). The eosinophils' reserve of cationic proteins and enzymes which imparts their profound parasiticidal effects (Butterworth and David, 1981) contrasts with this leukocyte's purported regulatory function in inflammation (Kay, 1985; Fechter et al., 1986). The opposing functions possessed by this leukocyte exemplify the enigma of the eosinophil. Recent evidence suggests that although the eosinophil does posses some regulatory capabilities, its presence is, in fact, a harbinger of tissue destruction (Gleich and Adolphoson, 1986, Wardlaw and Kay, 1987; Spry, 1988). Nor does the presence of the eosinophil automatically infer IgE mediated hypersensitivity, as evidenced by studies examining the interaction of the eosinophil with the cellular arm of the immune system (Basten and Beeson, 1970; Ruscetti et al., 1976; Beeson and Bass, 1977; Raghavachar et al., 1987; Ohnishi et al., 1988). The purpose of this review is to provide a brief overview of the structure and biology of the mammalian eosinophil and to emphasize the fact that eosinophils fulfil a paradoxical role as effectors of tissue damage and as benign modulators of inflammation. PMID- 1598764 TI - [The P300 component of the event-related brain potential in a short-term memory paradigm]. AB - In numerous investigations the P300-component of the event-related-brain potential (ERP) has proved a valid indicator of memory activities. The present study explores the amplitude of the P300 in an isolated short term memory task with variant difficulties. In two experiments the reproduction of senseless memory material was examined using the categories "syllables" and "consonants". One syllable was thereby synonymous with the so-called "chunk" which represents a subjective unit arising from grouping of memory material. The results show a significant increase in P300-amplitude in a line with memory load in both categories. On the contrary there is no significant difference in the amplitude of P300 between the two categories. These results suggest that the costs for storing one syllable are comparable with those for one consonant. PMID- 1598765 TI - [Serum, knee synovial fluid and joint tissue cefuroxime concentration in perioperative use before orthopedic interventions after tourniquet or in the bloodless field]. AB - A requirement to be met when administering perioperative prophylactic antibiotics as a standard with many orthopedic surgeons in artificial joint replacement is the achievement of sufficient concentrations of substance in the operative field. Following the i.v. short-infusion of 1.5 mg Cefuroxime-Sodium in 65 cases of knee joint surgery using a mid-thigh tourniquet substance levels were measured in samples of blood serum, synovial fluid and knee joint capsule. The Cefuroxime concentration in synovial fluids was found to be an average of 25.3 +/- 15.4 mcg/ml at the beginning and 14.9 +/- 10.7 mcg/ml at the end of the operations. Samples of joint capsule that had been taken during the operation showed substance levels of 20.6 +/- 11.1 mcg/ml. 13% of these samples showed substance levels below 4.0 mcg/ml which is the estimated breakpoint of full sensitivity of potentially infective bacteria. The relation of Cefuroxime concentrations in the synovial fluid to the length of time between the end of the infusion and the application of the tourniquet proved to be statistically nonsignificant (covariance analysis; p = 0.05). Nevertheless the determined differences showed a tendency which agrees with the findings of other authors who conclude, that a minimum exposure time of ten minutes is essential. PMID- 1598766 TI - [Rupture of the Achilles tendon. Causes and late results after surgical management]. AB - In a retrospective study 143 cases of surgically treated Achilles tendon ruptures were evaluated. The patients most commonly were male and between 31 and 40 years old. The majority of ruptures were sport injuries, mostly caused by indirect violence. The histological examination of the tendon very frequently revealed degenerative changes. 55 patients with unilateral Achilles tendon rupture were postoperatively evaluated by clinical examination and sonography. Because of the excellent functional and cosmetical results surgery remains the appropriate treatment of Achilles tendon rupture. PMID- 1598767 TI - [Sub-Achilles bursitis--a biomechanical analysis and clinical study]. AB - Chronic inflammations of the distal Achilles tendon correspond frequently to a mechanical irritation of the subcalcaneal bursa. On grounds of the biomechanical analysis an excessive inward bending of the hindfoot is postulated as the reason. So a conception for the clinical therapy is detected. The first measure will be a statics correction of the foot and a local application of antalgics. In case of unsuccessfulness after 3 months the surgical resection of the calcaneus exostosis is performed. After 3 months of conservative treatment 15 of 24 athletic patients are free of pain. The other 9 patients are free of pain 3 months after the surgical treatment. In either case all patients return to their former sports activity 6 months after the beginning of the treatment. PMID- 1598768 TI - [A treatment principle with questionable effectiveness in Perthes disease]. AB - The reduction of hip joint forces is a generally accepted part of the conservative treatment of Perthes disease. To reach this effect with help of splints (e.g. Thomassplint and the following models) does not seem to be efficient enough even from a clinical point of view. Theoretical considerations of former investigations of other authors point out the insufficient effect of these splints regarding the hip joint force reduction during the weight bearing phase in walking. The effect of these splints during the non-weight bearing phase in walking with regard to the hip joint forces has not been investigated so far. Therefore this paper is dealing with the forces onto the hip joint during the swinging phase of the leg with a splint, shown in a simplified, mechanical model. The results reveal significantly higher hip joint forces if the splint is used compared to the physiological forces during the swinging phase which in a static situation rise up to twice the body weight. These joint loadings are important because they occur during hip flexion and therefore cause pressure on the ventro cranial part of the head of the femur, a region which unfortunately is often involved in Perthes' disease and therefore especially vulnerable to these forces. From a biomechanical point of view the principle of reducing the hip joint forces with splints has to be abandoned. PMID- 1598769 TI - [Nerve compression syndrome caused by synovial cyst of the hip joint]. AB - Synovitis of the iliopectineal bursa have been described in pigmented villanodular synovitis, synovial chondromatosis, rheumatoid arthritis, osteoarthritis and necrosis of the femoral head. We report a case of enlargement of such a cyst in necrosis of femoral head and consecutive osteoarthritis, leading to entrapment of the femoral nerve. Simple drainage of the cyst did resolve pain for a short period and only elimination of the primum pathologicum agens did definitively release pain, irradiating to the ipsilateral leg. PMID- 1598770 TI - [Preliminary results of treatment with vascular pedicled iliac bone chip in femur head necrosis]. AB - For revascularisation of femoral head with osteonecrosis and pseudarthrosis of the femoral neck 68 femoral head were treated with a pedicled bonegraft. Therefore were taken the medial bonegraft (A. circumflexa ilium profunda) and the lateral bonegraft, based on the deep branches of the superior gluteal vessels. On the basis of postexamination it is reported about the first 35 patients, who were treated with a medial autological pedicled bonegraft. Prae- and postoperative each of them was clinical, radiological and angiological examinated. Because of this operation in 78.8% the clinical picture, existing about pain and the ability to walk and move, could be improved. PMID- 1598771 TI - [Follow-up analysis of total hip endoprosthesis after femoral neck fracture with and without previous operation]. AB - Damage occurring after joint-preserving surgical treatment of femoral neck- mostly femoral head necrosis of pseudoarthrosis-necessitates endoprosthetic joint replacement. In the case of inferior bone quality and unfavorable fracture forms as well as after failed conservative therapy, surgical treatment consists of implanting a total hip endoprosthesis. Between 1971 and 1989, 120 patients received total hip replacement after suffering fractures of the femoral neck: 61 patients did not have previous surgery, 59 patients had had joint-preserving surgery. Statistical analysis of the results showed that the primary stabilizing operation to preserve the joint did not have a negative influence on the survival probability of the total hip replacement in comparison with primary implantation. If the joint-preserving primary intervention fails, total hip replacement is a good choice for secondary surgery. In the case of complications such as femoral head necrosis or pseudoarthrosis the indication for total hip replacement should therefore be made early on. PMID- 1598773 TI - [Experimental study of laminectomy of the cervical spine]. AB - The influence of laminectomy on the statics of the cervical spine was experimentally investigated. Pressure tests were carried out with isolated supravital cervical vertebrae with and without intact vertebral arches. Changes occurring during the pressure test were registered by stretching measurement strips. We tried to determine the relation between the height of laminectomy and the dorsal forces being necessary for the maintenance of lordosis in another series of experiments. The experiments were taken with a model developed by ourselves. Following results were reached: The vertebral arch is involved in the interception of axial forces. It shores up the back bird of the vertebral body. This is only visible with reaching the breaking load. A dorsal flexion wedge tilting over in the spinal canal breaks off at vertebrae without intact vertebral arch. After a laminectomy the lordosis of the cervical spine can only be kept up by the increase of dorsal forces. The necessary increase of forces is biggest with the laminectomy of the second and fifth vertebra. A motion-study shows that there occurs a buckling in the area of laminectomy during flexion. PMID- 1598772 TI - [Indications and results of surgical treatment of neuromuscular scoliosis]. AB - The results of the operative treatment of 44 patients suffering from a neuromuscular scoliosis are presented. Only multisegmental procedures - also in combination with anterior methods - should be used to avoid a postoperative care with cast or brace. By means of the operation an average correction of the curves of 50.7% was achieved. The preoperative mean angle was 75.1 degrees, postoperatively a mean angle of 37.0 degrees (mean correction of 38.1 degrees) was determined. The preoperative angle, the duration of the operations, the blood loss and the quantity of the complications are higher than in idiopathic scolioses. As a result of the known tendency of deterioration in neuromuscular scolioses, the members of the Arbeitskreis Skoliose of the German Orthopaedic Society (DGOT) recommend an early operation (in progressing curves over 20 degrees) in patients suffering from a muscular dystrophy Duchenne. PMID- 1598774 TI - [Legal assessment of fractures and ruptures of the pelvis]. AB - Since it is very difficult to arrive at a complete picture of the very varied effects of fractures and ruptures in the pelvic region, the few studies that have so far dealt with the assessment of injuries to the pelvic girdle have been unable to develop any uniform guidelines. An analysis of the clinical, radiological and in particular CT studies that have been published to date shows that there is a well-defined relationship between clinical and radiological symptomatology. This allows cases to be assessed expertly and objectively. Where there are unstable pelvic girdle fractures, follow-up examinations can use the extent of symphyseal diastasis and the dislocation of one or both halves of the pelvis in relation to the sacrum as a yardstick to assess the effects of injury on the posterior pelvic girdle and their consequences - effects which would otherwise be difficult to detect. Only where there are symphyseal diastases of more than 15 mm with degenerative alterations of the sacroiliac joint and permanent dislocation of one half of the pelvis does an impairment of earning capacity of 20% apply. Impairment-of-earning-capacity rates of 30-40% are appropriate in cases with completely unstable pelvic girdle fractures involving dislocation of both halves of the pelvis and posttraumatic arthritis in the sacroiliac joints. All other pelvic girdle or iliac wing fractures qualify for a maximum 10% reduction in earning capacity, even if the symphysis has become rigid. PMID- 1598775 TI - [Tuberculous destruction of the talus--a rare form of extrapulmonary skeletal TBC -a case report]. AB - A 29 year old vietnamesian patient comes to an examination because of pain in the ankle one week after the arrival in Germany. The clinical examination is inconspicuous, x-ray pictures show a necrosis of the talus. A puncture is sterile. A partial astragalektomie is done. Histology demonstrates a tuberculosis. PMID- 1598776 TI - [Surgical treatment of para-articular ossifications after craniocerebral trauma]. AB - This article reports on 45 cases in which extra-articular ossifications were removed following cranial-cerebral traumata. Radiologically detectable relapses occurred in 6% of the patients only; however, in none of these cases did the relapses lead to reankylosis of the joint. In the sagittal plane, the average gain in mobility was an increase of 84 degrees in the hip joint and of 100 degrees in the elbow joint. Considerable complications were caused by four fractures in extremely osteoporotic bones. To reduce the fracture rate, surgery should be performed as soon as possible after bone maturation. In addition, treatment of patients with craniocerebral traumata and serious concomitant conditions requires an experienced rehabilitation team. PMID- 1598777 TI - [Adjuvant therapy (phenol, bone cement) in giant cell tumors]. AB - 69 patients were treated with giant-cell tumors in the Orthopaedic Department of the Semmelweis Medical School in Budapest between 1975-1989. The recurrence rate was 15 cases in 36 patients who were treated with curettage and spongiosa plasty only. In 11 cases the curettage was combined with adjuvants (phenol and/or filling with bone cement). This way the recurrence rate could be decreased to 1 case out of 11. The use of phenol and bone cement proved to be useful adjuvants to the surgical curettage at the giant-cell tumors and without complications. PMID- 1598779 TI - [The functional significance of the double afferent innervation of the heart]. PMID- 1598778 TI - [Critical considerations of the pathogenesis of "soft tissue rheumatism" (fibromyalgia) and its therapeutic consequences]. AB - The term "fibrositis" for generalized tendomyopathia that can still be found in Anglo-American literature is obsolete. The term implies that the disease has inflammatory qualities and can be treated by antiphlogistic means. Using light or electron microscopy we could find no evidence for an inflammatory process in the either tendon or muscle tissues. The term fibromyalgia makes clear that two totally different tissues are affected: 1. the bradytrophic collagenous connective tissue that requires little oxygen 2. the highly active skeletal muscles, made up of muscle cells that require a high amount of oxygen. The way these two tissues react to disorders therefore is also totally different: The collagenous tendon and capsular tissue react to lack of oxygen and overstrain by excessive formation of fibroblasts and dissolution of collagen fibres. Muscle tissue reacts to nerval irritations by pathological muscle tone in extensive areas of human body. This indurative myoitis does not lead to muscle damage, because the increased demand for oxygen is compensated by an increased supply. In the case of excessive focal contracture in myogelosis the tissue-pO2 sinks below the level vital to the muscle cells. By means of electron microscopy we could detect severe damage to, even dissolution of, myofilaments. Therapy for "muscular rheumatism" thus requires normalisation of the pathological tone with the help of antitonic substances or physiotherapy. PMID- 1598780 TI - [Current research on the role of memory in choice reactions]. PMID- 1598781 TI - [The dominant in the natural behavior of animals]. PMID- 1598782 TI - [Afferent control of the activity of the facial nerve nucleus]. PMID- 1598783 TI - [Synaptic processes in the activity of the red nucleus]. PMID- 1598784 TI - [Regulatory peptides in the lung]. PMID- 1598785 TI - [The hypothalamic mechanisms of arterial hypertension]. PMID- 1598786 TI - Primate responses to a vaccinia-rabies glycoprotein recombinant virus vaccine. AB - Over the past decade, a vaccinia-rabies glycoprotein (V-RG) recombinant vaccine virus has been developed for the potential control of wildlife rabies through oral immunization via baits. Prior to widespread field applications in varying ecological settings, extensive laboratory safety testing is necessary in a number of target and non-target species to quantify real or perceived risks and to monitor potential adverse health effects. Moreover, in order to mitigate concerns over inadvertent human exposure to a vaccine targeted for environmental release and intended for wildlife consumption, it was necessary to document the safety of the vaccine in primates following direct consumption orally and indirectly through transdermal administration. In the ensuing study, no significant differences were observed in the comparative pathogenicity of vaccinia and vaccinia-recombinant viruses by intradermal scarification of squirrel monkeys. In addition, eight of eleven chimpanzees administered the V-RG vaccine (10(9) plaque forming units/ml) per os developed rabies virus-neutralizing antibodies. Sentinel chimpanzee controls and human animal handlers did not show evidence of virus exposure. No adverse health effects were noted in any experimental animals as a result of V-RG vaccine administration. PMID- 1598787 TI - Live oral auxotrophic Shigella flexneri SFL124 vaccine with a deleted aroD gene: characterization and monkey protection studies. AB - Shigella flexneri SFL124, with a deletion encompassing all, or nearly all, of the coding sequence of gene aroD was obtained after selection on a fusaric acid medium supplemented with 2,3-dihydroxybenzoic acid for tetracycline-sensitive mutants of S. flexneri SFL114 which is an aroD::Tn10 transductant. Two of 20 tetracycline-sensitive mutants tested in colony hybridization with a 32P-labelled DNA probe of approximately 1400 base pairs (comprising all except the 75 N terminal base pairs of the coding region of gene aroD) did not hybridize. The selected mutant SFL124 is Congo-red positive, invades and shows a limited multiplication in HeLa cells and does not cause keratoconjunctivitis in guinea pigs. It is well tolerated by Macaca fascicularis monkeys, is excreted for up to 4 days, elicits a slight inflammatory reaction in the colonic mucosa, stimulates significant secretory IgA responses in the intestine and serum IgA and IgG responses against the S. flexneri cell envelope lipopolysaccharide. The immune response conferred a complete protection against challenge with 1 x 10(11) (equivalent to a 100 LD50 dose) live S. flexneri SFL1. PMID- 1598788 TI - Safety and immunogenicity of the live oral auxotrophic Shigella flexneri SFL124 in volunteers. AB - The live, aromatic dependent Shigella flexneri Y vaccine strain SFL124, with a deleted aroD gene, was tested for safety and immunogenicity in 21 healthy adult volunteers. A single dose of 2 x 10(9) live bacteria was given orally to ten volunteers, whereas 11 received three doses every other day. The vaccine was excreted for 4.2 days and was well tolerated by 90.5% of the vaccinees. Only 2 of 21 (9.5%) after the first dose had a self-limiting diarrhoea lasting 1 day; of volunteers given one dose only 3 of 10 showed anti-lipopolysaccharide (LPS) and anti-invasion plasmid coded antigen (Ipa) responses in serum. A faecal antibody response to LPS and Ipa was seen in six and three persons, respectively. Volunteers given three doses reacted with serum anti-LPS (9/11) and anti-Ipa (5/11) antibody responses. In stool, anti-LPS and anti-Ipa responses were detected in nine and eight volunteers, respectively. A booster dose of 2 x 10(9) bacteria given to six volunteers in the three-dose group 9-10 months later elicited high stool sIgA responses, indicating a strong mucosal memory, and was accompanied by a short excretion period of SFL124 (1.8 versus 4.2 days, p less than 0.05). The vaccination also elicited antibody-secreting cell (ASC) responses against LPS in peripheral blood: the three doses of the vaccine resulted in a stronger response than did the single dose, while the booster dose elicited only a limited ASC response. Volunteers previously exposed to shigellae exhibited stronger anti-Ipa responses in serum and stool suggestive of an immunological memory to the Ipa. The results indicate that SFL124 is a safe live vaccine strain inducing specific immune responses against LPS and Ipa with a mucosal immune memory lasting for at least 9 months. PMID- 1598789 TI - Statistical evaluation of virus titres of working standard of oral polio vaccine. PMID- 1598790 TI - Determination of lipoic acid in meat of commercial quality. AB - For the quantitative determination of lipoic acid in meat a sensitive GC/MS method in the chemical ionisation mode with methane as reactant gas has been developed. Firstly, the cleavage of protein-bound lipoic acid from the epsilon amino group of lysine residues was optimized by hydrolysing the synthesized model compound epsilon-lipoyllysine with several organic and inorganic acids and proteolytic enzymes. The concentrations of lipoyllysine and lipoic acid during this test hydrolysis were monitored by HPLC. Optimum hydrolytic conditions were heating at 120 degrees C in 2 mol H2SO4 for seven hours. After tissue hydrolysis, the lipoic acid in the hydrolysate was separated by a diethylether/sodium bicarbonate/diethylether extraction and then derivatised for GC with MBDSTFA. The highest amounts of lipoic acid in meat of commercial quality were detected in liver, heart and kidney whereas in muscle tissues its content was lower. PMID- 1598792 TI - [Thorium amd uranium in food of animal origin]. AB - The thorium and uranium contents (alpha-activities of the natural isotopes Th 228, Th-230, Th-232, U-234, and U-238) in several samples of the meat of domestic animals, venison, and cold-blooded animals are reported. The activity of thorium and of uranium was surprisingly constant in lean meat of all the animals tested. The average activity of the main isotope of thorium was 1-2 mBq Th-232/kg fresh meat (FM) and of uranium 21-34 mBq U-238/kg FM. The lowest and highest values observed were 0.4 and 2.7 mBq Th-232/kg FM, and 9 and 41 mBq U-238/kg FM, respectively. In some internal organs distinctly higher values were obtained: 8.6 mBq Th-232/kg in cattle bones, and 51 mBq U-238/kg in hog kidneys. The highest content of U-238, 84 mBq/kg, was observed in cuttlefish (whole animal). In lean meat, the activity of the daughter isotope Th-228 was on average (by factor) two to four times higher than that of the parent isotope Th-232. In cattle bones, and in fish samples including bones, the factor was 20 and 26, respectively. The activity of the isotope Th-230 ranged between Th-232 and Th-228. In all samples investigated, the daughter isotope U-234 showed an excess activity of 19 +/- 7% as compared to the parent isotope U-238. The above nuclides were determined alpha spectrometrically using Th-229 for thorium, and U-232 for uranium as internal standard. PMID- 1598791 TI - [HPTLC for the confirmation of results in the analysis of pesticide residues]. AB - HPTLC is an effective method for confirming gas-chromatographic results for insecticide and fungicide residues in sample solutions obtained by clean-up of fruit and vegetable extracts according to the Deutsche Forschungsgemeinschaft multiresidue method S 19. This study describes the possible interference caused by co-extractives from some crops rich in typical components, and gives the best operating conditions for separating and detecting the residues by HPTLC on silica gel and C18 reversed-phase material. The routine limit of determination was 0.01 0.05 mg/kg in most cases. PMID- 1598793 TI - [New approaches to revision of the psychoanalytic theory of development. II. The J. D. Lichtenberg concept and principles of a new psychoanalytic theory of development]. AB - Both D.N. Stern and J.D. Lichtenberg have outlined new models of a psychoanalytic theory of development taking into account the results of empirical infant research. The theory of Lichtenberg is described, whereas part I centered about the model of Stern. Both theories are discussed and central principles of development are specified: activity, social adaption, the influence of genetic factors, the importance of affect and a transactional model of development. PMID- 1598794 TI - [Tactile-symbiotic relationship as the earliest step of child development]. AB - Whereas Sigmund Freud considered the orality to be the beginning of the child development, in the last two decades the tactile-symbiotic mother-child relationship came into the center of scientific attention. The symbiotic narcissistic basal relationship of early childhood is reactivated in each later object relation. On this basis all active ego performances are built up, as e.g. the projective identification (archaic form), the identification, the transference (in psychotherapy), the regression etc. as well as the delimination from the object. The next level of the object relation is that of the free decision for or against an object. People with narcissistic personality disorders (narcissistic neuroses), having a constituent ego, and borderline personality disorders which occur in individuals with a fragmentation-prone ego, have suffered in their early childhood under deficiency experiences or the experiences of overprotection or of an attention under conditions. The more the individuals were disturbed also in their ego functions, the more an incapacity of the infant has to be supposed to experience or to admit the attention really presented to it. In major depressions the narcissistic emptiness or depletion seems to be at least partially the consequence of a genetic predisposition. PMID- 1598795 TI - [Are there two Freudian psychoanalytic dream theories?]. AB - According to the topographic theory and structural theory we find two explanations for the metapsychology of dream-generation. Both interpretations are complementary in some ways, but exclude in essential points. Consequences for the psychoanalytic theory of dreaming and the clinical practice are discussed. PMID- 1598796 TI - [The social network of families of HIV infected patients]. AB - This paper is focused at the social network of families of HIV-infected persons. 13 families were interviewed in a depth-psychological oriented semi-structured manner. The evaluation took place primarily according to a qualitative manner. The central result is that families with HIV-infected members inform more seldom other persons out of the informal social network in comparison to former coping tasks like haemophilia, dependence of drugs or homosexuality, events which happened before the HIV-infection. Accordingly to that only some single persons or whole families use informal help for their coping process with HIV-infection. The infected themselves claim more often professional psychosocial help, sometimes some relatives do it, seldom the whole family. We mostly find the familial tendency of social retreat and of coping with the burdens without help from the outside. This tendency is forced by distrust, social anxieties and projective separation of familial conflicts in order to maintain familial stability. PMID- 1598797 TI - [Significance of the transference-countertransference constellation in motivation for participation in an epidemiologic field study of psychogenic disorders: a report of experiences]. AB - The present article deals mainly with problems arising from the motivation of individuals for the participation in an epidemiological field study and their solutions on the basis of psychological-psychiatric findings. Subsequent to a more detailed survey of the research project in question formal and technical aspects of the motivational efforts (home visits, phone contacts) which had to be performed by the research group are mentioned. In the following the authors focus on the scientific concepts and orientations of their motivation work including the specific attention paid to the constellation of transference and countertransference. Particular importance is attributed to the presentation of several case studies which illustrate the influence of different psychoanalytical character traits on the motivational process. Finally the authors concentrate on specific problems regarding the sex of the probands as well as on their experiences with so-called hesitators i.e. individuals who for a longer period of time cannot decide whether to participate in the study or not. PMID- 1598799 TI - [Current viewpoints of research in differential indications for psychotherapy]. AB - The important results of research to differential indication for psychotherapy are discussed in their clinical relevance. As meta-analysis have shown, studies which compared the effects of different forms of psychotherapy could not give a clear answer to the question, which form of psychotherapy is indicated for a special type of patient and/or a special type of disease. This fact depends on the great conceptual and theoretical differences between the different forms of psychotherapy. It is postulated that the research of the differential indication between different therapeutic models which based on the same theoretical background e.g. psychoanalysis or behavioral therapy) will be more successful. At least empirical methods to control the differential indication for psychoanalytical treatments are discussed. PMID- 1598798 TI - [Diagnosis specific results of therapy of inpatient psychotherapy]. AB - Using the cases of 760 patients the therapy results of various diagnosis groups (ICD-diagnosis and structure diagnosis) were connected with the group specific therapy motivation values and the attitudes towards psychotherapy. The results show a strikingly poor performance of the patients with the ICD-diagnosis "hysterical neurosis" as well of the patients with a schizoid personality structure. In accordance with the results of Rudolf et al. therapeutic efficiency is lower in exactly those diagnosis groups where the motivational starting conditions stand in the way of a helpful therapeutic relationship. A high rate of impairment difficulty proved to be prognostically unfavorable independent of the respective ICD-diagnosis. PMID- 1598800 TI - [IL-2 potentiates the IL-3 production by ConA activated mouse splenic T cells]. AB - In addition to the regulation of T cell growth, IL-2 exerts effects on the induction of certain lymphokines. We show here that IL-2 synergizes with 5 micrograms/ml of ConA to promote the production of IL-3 in mouse splenic T cell cultures. IL-3 was measured as CFU-GEMM-inducing activity on mouse bone marrow progenitor cells in the supernatant of the stimulated mouse splenic T cells (TCM). The resting T cells produced no CFU-GEMM-inducing activity, but could be induced to produce low level of CFU-GEMM-inducing activity in the presence of ConA. In vitro exposure to IL-2 markedly increased CFU-GEMM-inducing activity production (nearly up to 8-fold) by the ConA-activated T cells. Optimal stimulation was observed when 80 u/ml IL-2 was used for 48 h incubation. Anti mouse IL-3 monoclonal antibody inhibited the CFU-GEMM inducing activity of TCM. Moreover, the TCM stimulated the proliferation of IL-3 dependent cell line FDC P1. We also show that IL-2 and ConA-treated T cells expressed high level of IL-3 mRNA through dot blot analysis. These results confirmed the nature of CFU-GEMM inducing activity of TCM as IL-3. The capacity of IL-2 to promote the production of IL-3 may represent an important mechanism by which it mediate the communication between the immune and hematopoietic systems. PMID- 1598801 TI - [Study on binding characteristics of 125I-labeled McAb LC-1 to lung adenocarcinoma cells in vitro and in vivo]. AB - McAb LC-1 was derived from fusion of myeloma cells and murine spleen cells immunized with human lung adenocarcinoma SPC-A-1 cells. The immunoglobulin isotype of LC-1 belonged to IgM. LC-1 was direct against the common epitope of lung cancer. It not only reacted with small cell lung cancer but also with non small cell lung cancer. LC-1 was purified from ascitic fluid by euglobulin precipitation and Sephadex G-200 filtration chromatography, and was iodinated with Iodogen, the specific reactivity of 125I-labeled LC-1 was determined by comparing standard curve with self-displacement curve. The immunoreactive fraction of 125I-LC-1 was determined by its binding to excess of antigen. The RIA data were plotted in Scatchard-form as binding of SPC-A-1 cells to LC-1. The binding constant of LC-1 binding to SPC-A-1 was 4.8 x 10(8) M-1. The LC-1 binding sites on SPC-A-1 were 7.2 x 10(4) per cell. The RIA inhibition test showed that LC-1 and LAC-122 (another IgM isotype McAb reacted only with non small cell lung cancer) had no cross-reactivity. The treatment of SPC-A-1 cells by proteinase and sodium periodate inhibited LC-1 binding to these treated target cells by 39% and 66% respectively. These results suggested that the biochemical nature of antigen recognized by LC-1 was glycoprotein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598802 TI - [Leydig cells--a normal cell model of cellular autophagy]. AB - In the present study, we tried to estimate, in a semiquantitative way, the relative frequency of the autophagic activity in various cell types under physiological condition. The results indicated that the highest activity appeared to be in the Leydig cells of rat testes. Autophagosomes were frequently observed in electron microscope photographs of Leydig cells, which provide a good model to study the autophagocytosis in normal cells. The autophagic process in Leydig cells was observed with the electron microscope in preparations treated to show CMPase activity. The mode of formation of autophagosomes in Leydig cells can be divided into three steps. Step 1, flattened membranous elements expand to enclose a small cytoplasmic territory to form pre-autophagosome. Step 2, The double membrane profile of the pre-autophagosome then completely encloses the cytoplasmic territory to form early autophagosome in which structurally normal organelles are contained. Step 3, the transformation of an early autophagosome into a late one is accompanied by the loss of one of the two delimiting membranes, the partial disintegration of the enclosed content and simultaneous acquisition of acid phosphatase activity. The enzymatic reactivity is acquired following a close association with the lysosomes. The late autophagosome then reaches the cell surface and appear to exocytose their residual content. PMID- 1598803 TI - Nursing from the other side--on having a long-term illness. PMID- 1598804 TI - Nurse abuse: inhumanity tolerated. PMID- 1598805 TI - AARN task force on direct access to nursing services. PMID- 1598806 TI - Pioneers: the challenges of self-employment in nursing. PMID- 1598807 TI - Medical profession stops the practice of a nurse practitioner: second update. PMID- 1598809 TI - Children with self-injurious behavior. PMID- 1598808 TI - Ready to go: using research in clinical practice. Interview by Doreen Reid. PMID- 1598810 TI - 1991--75th anniversary AARN. Our history--a proud heritage 1980-1991. PMID- 1598811 TI - PCA by epidural route (PCEA). PMID- 1598813 TI - PCA and cancer pain. AB - P.C.A. is a well known therapeutic strategy in analgesia. As this method has become a standard in postoperative analgesia, it becomes a nice alternative in cancer pain treatment when oral drug administration failed. In cancer pain treatment P.C.A. modality can be used in the subcutaneous or spinal administration route of drugs. The former is preferred because of its simplicity and lack of complications. In this presentation the P.C.A. spinal administration is discussed. The author obtained very good results with the continuous spinal administration of morphine. Recent literature data support the idea that P.C.A. bolus administration might prevent dose escalation. PMID- 1598812 TI - Psychological aspects of postoperative pain control. AB - This article examines the biological basis of emotional distress during postoperative pain, discussing the causal links between tissue injury and the mechanisms of centrally mediated emotional arousal. Neurologic signals from injured tissues induce spinoreticular transmission and extensive processing in limbic brain. Pain, as an emotion, shares central noradrenergic mechanisms with vigilance, a biologically important process. The emotional dimension of postoperative pain corresponds to perceived threat. Injury-induced activation of central noradrenergic mechanisms equips the patient for "fight or flight" just as in nature it equips a wounded animal for self-preservation actions. Although the brain chemistry of emotion prepares the postoperative patient to undertake some sort of survival-directed activity, most hospital settings do not permit patients to cope for themselves. This biologically mandated need to cope with injury has no avenue for expression. Several basic concepts from clinical psychology apply to the management of patients after surgery: Control, coping and self-efficacy. In light of the psychobiological nature of emotion in postoperative pain, they explain the benefits of therapies that encourage self-control such as patient controlled analgesia (PCA). PCA changes the role of the postoperative patient from passive to active, permitting patients in pain to cope actively for themselves. Moreover, it demonstrates that an integration of technological advances with psychological principles can improve patient satisfaction with care delivery. PMID- 1598814 TI - PCA and peripheral nerve blocks. PMID- 1598815 TI - Patient controlled analgesia and obstetrics. PMID- 1598816 TI - Stereo architecture of the interface of the epithelial cell layer and connective tissue core of the foliate papilla in the rabbit tongue. AB - The three-dimensional relationship between the epithelial cell layer and the underlying connective tissue core (CTC) of the foliate papilla of the rabbit tongue was studied by scanning electron microscopy after removal of the epithelial cell layer. The foliate papillae were fixed in Karnovsky's fixative, and the epithelial cell layers were exposed to long-term hydrochloric acid treatment (3.5 N HCl for 2-3 weeks at room temperature). The foliate papillae consisted of ridges and grooves located on the posterolateral margin of the tongue. They appeared as linear projections or ridges of lingual mucosa roughly perpendicular to the longitudinal axis of the tongue. These projections or ridges were parallel to one another and separated by grooves. After removal of the epithelium, two kinds of CTC folds appeared: one was the septal fold of CTC which runs in the central portion under each linear projection or ridge, and the other consisted of two sheets of groove side folds of CTC which run along both sides of the former and face the groove side epithelium. It was revealed that there are two sheets of septal epithelial processes, and each of them fits in between each septal fold and groove side fold of CTC. Numerous taste buds were located in the groove side epithelia, and their pores faced the surface of the groove. On the hollow surfaces that appeared on the surface of the groove side fold of CTC after removal of the epithelial cells with taste buds, nerve-terminal-like structures were encountered. Some openings of the ducts of small lingual glands were arranged linearly on the underside of the basal portion of each groove side epithelium. PMID- 1598817 TI - Immunogold identification of prolactin cells of goats in anoestrus, pregnancy and milk production: ultrastructural variations. AB - Prolactin (PRL) cells of the goat adenohypophysis have been identified by the IgG gold procedure with anti-sheep PRL serum. The secretion of these cells show differences in size and labelling in the three reproductive stages under study. Cells containing PRL can be grouped into low secretory activity cells (PRL-I) and high secretory activity cells (PRL-II) regarding their ultrastructure and functional significance. PRL-I were the most frequent cells in animals at the anoestrus stage, presenting numerous secretory granules and scarce development of the rough endoplasmic reticulum (RER) and Golgi complex (GC). At anoestrus and pregnancy stages there are frequent granule fusions, and the hormonal content partially disappears, perhaps by digestion. PRL-II cells were the most numerous at the lactating stage, presenting a moderate number of secretory granules and well-developed GC and RER. Some PRL-II cells of lactating animals exhibiting scarce granules and numerous exocytosis suggesting a high secretory activity. In both anoestrus and pregnancy stages most granules range in diameter from 450 to 750 nm, in contrast to the lactating stage in which most granules range in diameter from 150 to 450 nm. PMID- 1598818 TI - Morphological study on the convergence of the facial muscles at the angle of the mouth. PMID- 1598819 TI - Three-dimensional observations of accessory canals in mature and developing rat molar teeth. AB - The structure, distribution and formation of accessory canals in the developing and mature molar teeth of rat mandibular jaws were investigated with scanning electron microscopy and with three-dimensional image analysis using serial light microscopic sections. In the initial stage of the accessory canal formation, most of the canals appeared in the gaps of the epithelial root sheaths formed by their approaching each other in the initial stage of the root formation. However, some of the canals appeared in the slits which may be formed by the destruction of the epithelial root sheath in the root apex regions. When the gaps and slits were invaded by blood vessels, the regions surrounding the vessels did not mineralize but became accessory canals. Usually, an accessory canal with one blood vessel connected the periodontal ligament to the dental pulp; however, in some cases, the canals were broken off midway following the destruction of the vessels. PMID- 1598820 TI - Effects of mesenchyme of the embryonic urogenital sinus and neonatal seminal vesicle on the cytodifferentiation of the Dunning tumor: ultrastructural study. AB - The aim of the present study was to examine the effects of mesenchyme on the cytodifferentiation of the Dunning tumor (DT, R3327), a transplantable rat prostatic adenocarcinoma developed spontaneously from the dorsolateral prostate of a Copenhagen rat. Small pieces of DT were combined with mesenchyme of the rat urogenital sinus (18-day fetal, UGM) or seminal vesicle (0-day neonatal, SVM). Both types of combinations were grown under the kidney capsule of male athymic nude mice for 4 weeks. At harvest, the tissue recombinants were fixed and processed for electron microscopy. Grafts of parental DT were similarly processed for electron microscopy. The tumor was characterized by tubules lined by 2-3 layers of undifferentiated cells lacking secretory granules. The basal lamina was reduplicated, and epithelioid cells traversing gaps in the basal lamina were frequently observed. The stroma was composed of a mixture of fibroblastic and large epithelioid cells derived from the ductal lining epithelium through a process of micrometastasis. In UGM or SVM+DT combinations the mesenchyme influenced the differentiation and secretory activity of the DT epithelium. The induced DT epithelial cells exhibited a well-developed granular endoplasmic reticulum, a large Golgi apparatus and prominent secretory granules which were never observed in the parental DT. The basal lamina returned to normal, while the incidence of micrometastasis was decreased. The collagen content of the stroma was increased with a concurrent appearance of smooth muscle cells surrounding those tubules where secretory cytodifferentiation had occurred. While the mechanism involved in the mesenchyme-induced change in cytodifferentiation remains unknown, it is evident that the DT epithelial cells when associated with normal embryonic or neonatal mesenchyme can express a more normal cytodifferentiation and function. It is concluded (a) that the DT cells can be induced by mesenchyme to express more highly differentiated ultrastructural patterns and secretory cytodifferentiation, (b) that the induced secretory cytodifferentiation is associated with a reduction in invasiveness (micrometastasis) and a more normal-appearing basal lamina and (c) that the increased abundance of collagen fibers and the differentiation of smooth muscle in the stromal compartment are associated with secretory cytodifferentiation suggesting that reciprocal epithelial-mesenchymal interactions are involved in the regulation of the pathobiology of the DT. PMID- 1598821 TI - Abnormal elevation of the neural folds in the loop-tail mutant mouse. AB - The processes of elevation and convergence of the spinal neural folds were analyzed in normal (+/+; Lp/+) and abnormal (Lp/Lp) embryos of the loop-tail mutant mouse in order to determine possible mechanisms underlying the dysraphic defect characterized by a failure of the neural fold to close in this mutant. The results indicate that the neural folds are already defective during very early phases of elevation, with greater distances between the apical points of the paired walls of the neural groove, larger ventral angles and higher ratios of luminal/basal linear distances occurring in the abnormal embryos relative to those in normal embryos. The cross-sectional area of the neuroepithelium is also greater in abnormals, suggesting that faulty elongation of the neuraxis may contribute to the dysraphic condition. PMID- 1598822 TI - Iron overload of the liver by trimethylhexanoylferrocene in rats. AB - Iron-deficient female Wistar rats were fed a diet, which contained 0.5% trimethylhexanoylferrocene, over a 56-week period. This dietary iron loading resulted in a progressive siderosis and enlargement of the liver with a maximum iron content of 947.0 +/- 148.0 mg (vs. 0.07 +/- 0.04 mg in iron deficiency) and a maximum organ weight of 39.4 +/- 6.6 g (vs. 6.9 +/- 1.4 g in iron-deficient control rats). Up to 43 weeks, whole liver iron rose by increase in iron concentration (max. 28.0 +/- 6.1 mg/g wet weight, w.w.) as well as by enlargement of the organ. Afterwards whole liver iron increased solely by ongoing hepatomegaly. At the commencement of iron loading, stainable iron was almost exclusively stored by hepatocytes equally throughout all areas of the liver lobule. Later, the distribution of iron-loaded hepatocytes became strikingly periportal, and, in addition, Kupffer cells as well as sinus-lining endothelia began to store iron. Animals with a liver iron concentration of more than 10.4 +/ 0.75 mg/g w.w. showed no further increase in ferritin and haemosiderin within hepatocytes. Iron-burdened Kupffer cells/macrophages, however, accumulated permanently, hereby forming intrasinusoidal and portal siderotic nodules and areas. First signs of liver damage such as necrosis of single hepatocytes and mild fibrosis began at a liver iron concentration of 14.7 +/- 1.4 mg/g w.w. With advancement of iron loading, focal necrosis of hepatocytes and iron-burdened macrophages took place, and significant perisinusoidal as well as portal fibrosis developed. Cirrhosis, however, the final stage of impairment in iron overload of the liver in humans, could not be induced in this animal model up to now. PMID- 1598823 TI - Antagonism of l-stepholidine on D2 receptor-mediated inhibition of synaptosomal adenylate cyclase in rat corpus striatum. AB - In the presence of Sch 23390 0.1 mumol.L-1, dopamine (DA) inhibited the activity of synaptosomal adenylate cyclase (AC) isolated from rat striatum in a concentration-dependent manner with IC50 value of 2.2 mumol.L-1. The maximal inhibition corresponded to a 51% decrease of basal enzyme activity and was obtained at DA 100 mumol.L-1. The inhibitory effect of DA was reversed by selective D2 receptor antagonist spiperone 10 mumol.L-1. N-0437, a selective D2 DA receptor agonist also inhibited the activity of AC in the manner similar to that of DA. Both the inhibitions induced by DA and N-0437 were antagonized by l stepholidine (l-SPD). However, in the presence of Sch 23390, l-SPD alone also inhibited the activity of AC by 29% and 33% at the concentrations of 10 and 100 mumol.L-1, respectively. The inhibition of l-SPD on AC activity was significantly antagonized by spiperone. In the presence of Sch 23390, both DA and N-0437 increased the activity of high affinity GTP phosphohydrolase in striatal synaptosomes. The increases of GTP phosphohydrolase activity stimulated by DA and N-0437 were completely reversed by l-SPD 100 mumol.L-1. These results suggest that l-SPD antagonizes or reverses the D2 receptor-mediated inhibition of AC activity through affecting the regulation of Gi (inhibitory guanine nucleotide dependent protein) on D2 receptor-coupled AC and therefore affects the negative feedback of presynaptic DA receptors. Moreover, the inhibition of AC activity induced by l-SPD alone may provide a useful biochemical index for dual action of l-SPD. PMID- 1598824 TI - Pharmacokinetics and relative bioavailability of ofloxacin tablets in 12 healthy volunteers. AB - Single oral dose of tablet A (Daiichi Pharmaceutical Co Ltd, Japan) and B (Jining Pharmaceutical Factory, Shandong, China) of 300 mg ofloxacin (Ofl) were given to 12 Chinese healthy male volunteers in an open, randomized crossover study. Drug concentrations in serum and urine were assayed by HPLC and partial least squares spectrophotometric method, respectively. The serum concentration-time course after medication conformed to a 2-compartment open model with a first order absorption. Pharmacokinetic parameters after tablet B did not differ significantly from the corresponding values after tablet A. The bioavailability of tablet B was comparable to that of tablet A. PMID- 1598825 TI - Anti-shock effect of cyproheptadine in rabbit. AB - Twenty four New Zealand rabbits were equally divided into a cyproheptadine (Cyp) treated group and a control group. Profound hemorrhagic shock was produced by exsanguination via carotid artery until mean arterial pressure (MAP) = 5.3 kPa (40 mm Hg) for a period of 90 min. After given Cyp 10 mg.kg-1, the MAP and central venous pressure (CVP) of the treated group rose obviously (P less than 0.01) and the mesenteric microcirculation improved markedly. After 1 h, all indices returned nearly to the preshock state. The survival rate 2 h after Cyp increased to 12 (P less than 0.01) in comparison with the control group (7). The results showed that Cyp, which dilates the vasculature and improves the microcirculation through blocking serotonin S2 and histamine H1 receptors, has a beneficial anti-shock effect. PMID- 1598827 TI - Rate- and voltage-dependent effects of m-nisoldipine on action potential of partially depolarized guinea pig papillary muscle. AB - The rate- and voltage-dependent effects of m-Nis were studied using standard microelectrode technique and real-time microcomputer analyzing system. The onset rate for rate-dependent inhibition (RDI) on action potentials of partially depolarized papillary muscle of guinea pig was accelerated as the concentration of m-Nis was increased from 0.5 to 2 mumol.L-1 or the driving frequency decreased from 0.8 to 0.2 Hz. The steady-state values of Vmax and APA were markedly decreased by elevating the concentration of m-Nis or increasing the driving frequency. The recovery time constants of Vmax, APA, and latency period from RDI were all increased by m-Nis (1 mumol.L-1). The inhibitory effects of m-Nis on Vmax and APA were more pronounced as the resting membrane potential was decreased by elevating K+ concentration in the perfusate. PMID- 1598826 TI - Cardiovascular effects of intracerebral injection of neuropeptide Y in rats. AB - Cardiovascular effects of microinjection of neuropeptide Y (NPY) (25, 50, and 100 pmol/site) into field CA3 of hippocampus (CA3), lateral septal nuclei (LSN) and substantia nigra (SN) were investigated in urethane-anesthetized rats. NPY administered into CA3 produced a dose-dependent hypotension and bradycardia. Maximal changes of mean arterial blood pressure (MAP) were -1.5 +/- 0.7, -2.0 +/- 0.4, and -4.2 +/- 1.6 kPa, respectively; maximal changes of heart rate (HR) were 7 +/- 14, -23 +/- 24, and -64 +/- 50 bpm, respectively. NPY microinjection into LSN produced a dose-dependent increase in MAP (0.9 +/- 0.8, 1.3 +/- 0.5, and 3.1 +/- 0.5 kPa, respectively) and a prominent increase in HR (14 +/- 15, 41 +/- 28, and 42 +/- 31 bpm, respectively), but the tachycardia was not dose-dependent. NPY applied into SN elicited a dose-dependent decrease in MAP (-1.0 +/- 0.5, -2.2 +/- 0.9, and -4.3 +/- 2.0 kPa, respectively), but no statistically significant change in HR. The results showed that exogenously applied NPY has distinct cardiovascular effects in CA3, LSN, and SN. PMID- 1598828 TI - Effects of m-nisoldipine and nisoldipine on electric activity of human atrial tissue. AB - Using intracellular microelectrode technique and microcomputer analyzing system, the effects of m-nisoldipine (m-Nis) and nisoldipine (Nis) on spontaneous electric activity of human atrial tissue were studied. APA and Vmax were remarkably decreased by m-Nis (0.25 and 1.25 mumol.L-1) and Nis (0.25 mumol.L-1). RPF was also greatly decreased as a result of inhibition in VDD. The inhibitory effects of m-Nis on transmembrane potentials were less than those of Nis at equal concentration (0.25 mumol.L-1). Neither MDP nor APD90 was affected by m-Nis and Nis. PMID- 1598829 TI - Influence of methionine-enkephalin on interleukin-2 production and interleukin-2 receptor expression. AB - Influences of methionine enkephalin (met-enk) on delayed hypersensitivity (DH) against 2,4-dinitrofluoro-benzene (DNFB) and interleukin-2 (IL-2) production of mouse lymphocytes were examined. Met-enk enhanced the DH response to ear challenge when mice were treated with met-enk beginning at the same time as cpicutaneous sensitization with DNFB but not after being sensitized. When met-enk (10 nmol.L-1-100 mumol.L-1) was included in Con A-stimulated lymphocyte cultures, the IL-2 production increased in a concentration-dependent manner. Furthermore, in vivo treatment with met-enk also increased IL-2 production of splenocytes, and the enhancement of IL-2 production was parallel to that of lymphocyte proliferation. However, met-enk 10 nmol.L-1 had no effect on IL-2 receptor expression on thymocytes, splenocytes, and gut-associated lymphocytes. The data suggested that the stimulative effect of met-enk on lymphocytes may be mediated through the increase of IL-2, but not through the IL-2 receptor expression. PMID- 1598830 TI - Effects of copper and selenium on electric parameters of cultured myocardial cells damaged by xanthine-xanthine oxidase. AB - Addition of xanthine 0.42 mmol.L-1 and xanthine oxidase 5.3 nmol.L-1 (X-XO) to the culture medium increased the amplitude of ESR spectra of myocardial cells, demonstrating an increase in free radical contents; diminished the action potential parameters significantly and reduced the input impedances from 0.34 +/- 0.11 to 0.24 +/- 0.1 M omega, expressing a typical electrical appearance of membrane damage. Supplying Cu 62.5 ng.ml-1 and/or Se 173 ng.ml-1 to the medium brought all of the electric parameters and the free radical content of myocardial cells back to normal. The results indicate that both the two trace elements are able to scavenge free radicals, thus antagonizing X-XO, which induces damage to myocardial cells. PMID- 1598831 TI - [Effects of caffeine on shuttle, operating behaviors, and brain metabolism in rats]. AB - Effects of caffeine (30, 60, and 120 mg.kg-1, ip) on shuttling and operating behaviors in 80 rats were studied. Effects of caffeine (60, 120 mg.kg-1, ip) on contents of dinucleotides and pterins in 6 brain areas of 18 rats were investigated by HPLC with fluorescent detector. The results showed that the dose of caffeine that induced augment of shuttle behavior was lower than that induced operating behavior. Caffeine 120 mg.kg-1 inhibited both shuttling and operating behavior, decreased FAD content in caudate nucleus; caffeine 60 mg.kg-1 increased FAD in cerebellum and brain stem. Caffeine 60, 120 mg.kg-1 increased brain NADH contents, decreased pterin contents, and increased biopterin contents in some brain areas. PMID- 1598832 TI - [Inhibition of ohmefentanyl on articular afferent-induced responses of neurons in the spinal lamina X]. AB - In 37 neurons of spinal lamina X, nociceptive responses were evoked by stimulation of the posterior articular nerve (PA) innervating the joint of hindlimb in anesthetized cats. Profound inhibition of nociceptive responses in 73.3% of neurons was induced by ohmefentanyl (1-2 micrograms.kg-1, iv), which was completely reversed by naloxone (80-330 micrograms.kg-1, iv). The results suggested that the mu-opioid receptors was involved in the regulation of transmission of nociceptive information in the spinal lamina X. PMID- 1598833 TI - [Triggered activities induced by cesium chloride and terminated by drugs in cat heart in vivo]. AB - Monophasic action potential (MAP) of the left ventricular epicardium in vivo in 58 cats were recorded by using a contact electrode. The results showed that early after depolarization, delayed after depolarization, oscillatory afterpotential, and some kinds of triggered arrhythmias were induced by CsCl (iv 0.5 mmol.kg-1), that these afterdepolarizations and triggered arrhythmias were prevented by sodium valproate, and that ventricular tachycardias induced by CsCl was terminated by lidocaine, moricizine, and sodium valproate. PMID- 1598834 TI - [Determination of m-nifedipine and its pharmacokinetic study in rabbits by high pressure liquid chromatography]. AB - A high-pressure liquid chromatographic method was developed for determination of m-nifedipine in plasma using a chemical bonded C-18 phase column (YWG-C18 10 microns, made in China) with nitrendipine as internal standard. To increase life of the YWG-C18 column a mixture of methanol and 5 mmol.L-1 phosphate buffer (70:30 vol/vol) was selected as mobile phase with a flow rate of 0.8 ml.min-1. The method was sensitive to m-nifedipine 3 ng.ml-1 plasma and the standard curve was linear from 10 to 1000 ng.ml-1 with correlation coefficient of 0.99. The within-day and day-to-day precisions (CV) of this method were 4.5% and 7.0%, respectively, with recoveries of 95-102% (10-1000 ng.ml-1). There was no interference with nifedipine, amiodarone, propranol, and verapamil. A pharmacokinetic study on m-nifedipine was carried out in 8 rabbits. A better computer fitted to a two-compartment model was observed using 3P87 program. The parameters obtained were as follow: Vc 6.3 L.kg-1, Cl 0.021 L.kg-1.min-1, T1/2 alpha 30 min, T1/2 beta 230 min, AUC 102 micrograms.min.ml-1. PMID- 1598835 TI - [Protective effects of tetrahydroprotoberberines on experimental myocardial infarction in rats]. AB - The protective effects of tetrahydroprotoberberines (THPB), viz., l tetrahydropalmatine (THP), l-stepholidine (SPD), and tetrahydroberberine (THB) on experimental myocardial infarction by ligating the left coronary artery were estimated in rats. The myocardial infarction size (MIS) was determined by nitro blue tetrazolium technique. THP, SPD, and THB, as well as propranolol, played a remarkable role in diminishing the MIS within 24 h and decreasing the rise of creatine kinase (CK) and aspartate aminotransferase (AST) in the serum within 4 h after the ligation of the coronary artery. Among these drugs, SPD provided the myocardium with the best protective benefit. Systolic and diastolic blood pressures (SBP and DBP) were rapidly lowered after SPD 2.5 mg.kg-1 iv by 39.5% and 48.5%, respectively. The value of the MBP x HR x LVET was concomitantly decreased by 35.1% in the anaesthetized rats. The myocardial contractility and diastolic compliance were not implicated during the experimental regimen. The prophylactic administration of SPD 2.5 mg.kg-1 improved the cardiac hemodynamic alterations caused by ligating the left coronary artery. SPD depressed the elevation of T and LVEDP, and reduction of +dP/dtmax, Vpm, and Vmax besides complete resistance to the reduction of -dP/dtmax and LVSP, underlying the precautions against the damage of the myocardial contractility and diastolic compliance, especially the latter. PMID- 1598836 TI - [Cardiovascular effects of kainic acid injected into habenular nucleus]. AB - The present study was to determine if the cardiovascular effect being produced by exciting cells in the habenular nucleus (Hab). Experiments were performed on urethane-anesthetized rats. Microinjection of kainic acid into Hab demonstrated dose-dependent increases in arterial blood pressure and heart rate, accompanied by other sympathetic reactions, such as mydriasis and pilo-erection. But microinjection of lidocaine into Hab did not elicit similar effects mentioned above. PMID- 1598837 TI - [Pharmacokinetic analysis of enterohepatic circulation of piroxicam in rabbits]. AB - The concentration (c)-time (t) curves of piroxicam showed double peaks following iv 10 mg dose to 4 rabbits. A new mathematical model of enterohepatic circulation was proposed to explain this double-peak phenomenon and showed good agreement with data. This model provides not only the common pharmacokinetic parameters: T1/2 = 1.12 +/- 0.32 h, V1 = 0.64 +/- 0.12 L, AUC = 34.7 +/- 7.8 micrograms.h 1.ml-1, but also the parameters of enterohepatic circulation of piroxicam: the cycling amount of drug Db = 3.9 +/- 1.4 mg, reabsorption fraction Fb = 0.50 +/- 0.04, reabsorption rate constant Ka = 2.55 +/- 0.50 h-1. It is indicated in this study that enterohepatic circulation results in a 20% average increase of the effective amount of piroxicam. PMID- 1598838 TI - [Lack of mutagenicity and teratogenicity of 16-methylene-17 alpha-acetoxy-19 norprogesterone]. AB - 16-Methylene-17 alpha-acetoxy-19-norprogesterone (ST-1435) is a new antifertility agent. ST-1435 silastic capsule was implanted sc in the nuchal region of rats on d 6 of gestation at 75, 300, and 600 mg.kg-1. The rats were killed on d 20. In comparison with the control, the treated groups showed no significant differences in maternal body weights, number of corpora lutea, and the development of embryos and fetuses. The number of dead fetuses decreased and live fetuses increased slightly. ST-1435 did not affect the frequency of micronucleated polychromatic erythrocytes, nor induce chromosomal aberrations in cultured CHL cells, or increase the revertants of Salmonella typhimurium TA97, TA98, TA100, and TA102 in Ames test. The results suggested that ST-1435 had neither teratogenicity nor mutagenicity. PMID- 1598839 TI - [Inhibition of photosensitization of morin on DNA synthesis of ascites hepatoma cells]. AB - Morin (0.012, 0.12, 1.2, 12.0 micrograms.ml-1) significantly inhibited the DNA synthesis of ascitic hepatoma (AH) cells. The inhibition of DNA synthesis and cell mortality was dependent on its concentrations as well as the illumination time. Photosensitization of morin was not due to 1O2 and O2-, but closely related to OH. and H2O2. The mechanism of the inhibition may be attributed to the damage of DNA replication template. PMID- 1598840 TI - [Biotin-avidin-ELISA for cytotoxin purified from cobra venom]. AB - A technique combining the biotin-avidin amplifying system with sandwich enzyme linked immunosorbent assay (B-A-ELISA) was developed for the microassay of the cytotoxin from Naja naja atra venom. The horse-peroxidase was used as the marker and polystyrene microhemagglutination plates as solid carrier. The sensitivity was 0.5 ng.ml-1. The assay range was 1.25-320 ngml-1 with coefficient of variation of 4.9% (intragroup) and 8.1% (intergroups), respectively. PMID- 1598841 TI - Is rapid performance improvement across short precue-target delays due to masking from peripheral precues? AB - The role of lateral masking in more rapid performance improvement with peripheral than with central precuing was investigated. A peripheral precue to the inside of the target location provided less masking at zero precue-target delay than a precue to the outside (experiment 1) or a precue involving a partial target at the target location (experiment 2). There was no significant interaction between precue-target delay and precue type in a comparison of inside precues and precues involving a briefly-brightened box around the target location, although overall performance was significantly poorer with the latter (experiment 3). Performance was better at short precue-target delays with inside precues than with central precues (experiment 4), yet it did not improve significantly more rapidly. Minimizing lateral masking with peripheral precues thus eliminates the dramatic performance improvement sometimes observed across short precue-target delays, causing performance to be consistently better than with central precues across these delays. PMID- 1598842 TI - Effects of multiple reference points in spatial stimulus-response compatibility. AB - In two experiments, spatial stimulus-response compatibility effects in situations where the stimulus could appear in eight different locations were investigated. The locations were obtained as a result of orthogonal manipulation of hemispace, visual hemifield within hemispace, and relative position within hemifield. In the first experiment, only relative position within hemifield was relevant for selecting one of two responses (left or right). The results showed that both hemifield and relative position formed the basis of compatibility effects. In the second experiment, which was in most respects identical to the first, all spatial information was irrelevant. Only the geometrical shape of the stimulus determined the correct response. The results showed three S-R compatibility effects, based on hemispace, hemifield, and relative position. These results contradict earlier findings, and have implications for models of stimulus-response compatibility. PMID- 1598843 TI - Visual scanning with or without spatial uncertainty and divided and selective attention. AB - An experiment was conducted to address the relation between theories of selective attention and theories of divided attention by examining the pattern of task interference between visual scanning as a sequential and selective attention process and other concurrent spatial or verbal processing tasks. A distinction is proposed between visual scanning with or without spatial uncertainty regarding their possible differential effects on interference with other concurrent processes. The experiment required the subjects to perform a primary tracking task, which was concurrently performed with a secondary spatial or verbal decision task. The relevant information that was needed to perform the decision tasks was displayed with or without spatial uncertainty. The results provide evidence that visual scanning as a spatial exploratory activity produces greater task interference with concurrent spatial tasks than with verbal tasks. Furthermore, spatial uncertainty in scanning is identified to be the crucial factor in producing this differential effect. PMID- 1598844 TI - Influence of processing speed on adult age differences in working memory. AB - Two studies are reported in which adults ranging from 18 to 80 years of age performed tasks designed to measure working memory functioning and perceptual comparison speed. The results from both studies indicated that statistical control of the measures of perceptual comparison speed greatly attenuated the age related variance in measures of working memory even when working memory was assessed under self-paced conditions. Additional results in the second study supported the hypothesis that the speed influence was manifested in the rate of activating information rather than in the rate at which it was lost as a function of time or other processing. PMID- 1598845 TI - The role of frame size on vertical and horizontal observers in the rod-and-frame illusion. AB - The rod-and-frame illusion was used to examine a proposed distinction between the mechanism responsible for frame effects on rod-adjustment errors with large displays and the mechanism responsible for errors with small displays. It was suggested that visual-vestibular mechanisms are involved only when the rod is surrounded by a large tilted frame. Errors in the perceived vertical with small frame would instead be due to purely visual mechanisms. To examine this dual process model, we compared errors at small and large frame when the body was vertical or horizontal. There is evidence to suggest that tilting the body affects visual-vestibular interactions, but there is no reason to expect that body tilt would affect intravisual interactions. Hence, we hypothesized that body tilt would increase errors for large frame, but not for small frame. Eight subjects were tested in four different conditions, corresponding to the combination of two body orientations (vertical versus horizontal) and two frame sizes (47.5 versus 10.5 deg of visual angle). Fourier analysis of data was performed. Repeated measures ANOVA tested the hypothesis about frame size and body orientation. The hypothesis was not confirmed. More specifically, we found that tilting the body increased errors for the small frame as well as for the large frame. The interaction between frame size and body orientation was not significant. Results are discussed in relation to the proposed dual-process model. PMID- 1598846 TI - Differences in the respiratory burst of human polymorphonuclear leukocytes induced by virulent and avirulent Legionella pneumophila serogroup 1. AB - Two strains of Legionella pneumophila of different virulence were examined for their influence on the metabolic oxidative activity of human polymorphonuclear leukocytes. The leukocytes exhibited decreased rates of oxygen consumption and diminished chemiluminescence activity following phagocytosis of a virulent strain of L. pneumophila serogroup 1. In contrast, phagocytosis of its multipassaged derivative rendered avirulent, was accompanied by increased rates of both oxygen consumption and chemiluminescence activity. Although no differences were observed in oxygen uptake induced by the virulent legionellae compared to leukocytes at rest, statistically significant differences were observed in the chemiluminescence responses. These observations were not unexpected, since the luminol-enhanced chemiluminescence assay, is more sensitive than the oxygen uptake assay. In spite of decreased metabolic activity of PMN in the presence of virulent legionellae, electron microscope studies showed higher numbers of intracellular L. pneumophila than the avirulent subtype. Thus, virulent and avirulent L. pneumophila can be differentiated on the basis of oxygen consumption and chemiluminescence assays. PMID- 1598848 TI - Bioluminescence and chemiluminescence literature. The 1991 literature:Part II. PMID- 1598849 TI - Bioluminescence and chemiluminescence literature. The 1982 literature: Part I. PMID- 1598847 TI - Leukocytes as immunosensors: an immunoassay without labelled reagents. AB - A novel quantitative nonlabel immunoassay is described. It is based on the recognition of antigen-antibody complexes by the Fc-receptors of phagocytic leukocytes and the subsequent activation of these cells. Activation which is proportional to the amount of immune complexes present can be detected by measuring the intensity of chemiluminescence emitted by the activated cells. In addition to determinations of an antigen and an antibody, the binding capacity of complement to antigen-antibody complexes can be estimated. PMID- 1598850 TI - A survey of more than 90 commercially available luminometers and imaging devices for low-light measurements of chemiluminescence and bioluminescence, including instruments for manual, automatic and specialized operation, for HPLC, LC, GLC and microtitre plates. Part 1: Descriptions. AB - This survey was compiled in January and February 1992 from information available in public domain literature requested by and supplied to the author by numerous companies in the previous two months. More than 90 luminometers (manual, automatic, microtitre plate, HPLC, LC, GLC, imaging and specials) from more than 60 companies are included. Each company was invited to supply company brochures, technical details, user manual and information about software and any other information concerning their product(s). The response varied from a single information sheet to promotional material and up to full product information and specification with technical details, user manuals and scientific publications. Where an instrument is dedicated to a single task the company may have only provided details relevant to accomplishing that task. Part 2 of this survey will contain photographs of some of the luminometers. It is intended that updates to this review will be published at least annually in this journal and suppliers are invited to provide full technical details of new luminometric equipment to the author. PMID- 1598851 TI - Pathophysiology of experimental bovine endotoxicosis: endotoxin induced synthesis of prostaglandins and thromboxane and the modulatory effect of some non-steroidal anti-inflammatory drugs. AB - Endotoxin-induced synthesis of thromboxane A2 (TXA2), prostacyclin (PGI2) and prostaglandin E2 (PGE2) was studied in 3 cows after intravenous E. coli endotoxin (055:B5-0.025 mg/kg b.w.) administration. Blood sampling and monitoring of clinical signs were performed from 2 h prior to until 6 h after endotoxin challenge. Blood samples were analyzed for stable hydrolysis products of TXA2 (TXB2), PGI2 (6-keto PGF) and PGE2 (bicyclic PGE2), biochemical and haematological parameters. In a similar experimental design the efficacy of the non-steroidal anti-inflammatory drugs (NSAID) flunixin meglumine (FM) and phenylbutazone (PB) in suppressing eicosanoid synthesis and clinical signs in response to endotoxin challenge was investigated. Two groups of cows, each comprising 2 animals, were treated with FM and PB prior to endotoxin challenge. It was observed that plasma concentrations of TXB2, 6-keto PGF and bicyclic PGE2 increased rapidly after endotoxin challenge. Concentrations were significantly elevated for hours and were correlated to the severity of clinical signs of endotoxicosis. Pretreatment with NSAID suppressed mediator production and alleviated clinical signs. The experiments suggest a certain pathophysiological role of TXA2, PGI2 and PGE2 for the early systemic ill-effects of bovine endotoxicosis. PMID- 1598852 TI - A simple test for the demonstration of abomasal juice in rumen samples of young calves. PMID- 1598854 TI - The prevalence of toxoplasma antibodies in swine sera in Finland. AB - A total of 1847 swine sera obtained from the 10 largest abattoirs slaughtering swine in Finland were examined by ELISA for toxoplasma antibodies. The sample represented 0.64% of the total number of swine slaughtered in these abattoirs over a period of 2 months. The prevalence of toxoplasma antibodies in swine sera was 2.5%. PMID- 1598853 TI - Relationship between testicular measurements, body weight and semen quality in young dairy bulls. AB - Dairy bulls, 322 Ayrshires (Ay) and 85 Friesians (Fr), were studied at the age of 11 months. Of the bulls, 286 Ay-bulls and 80 Fr-bulls produced semen of acceptable quality for use in A.I. Scrotal circumference, tonometer measure, scrotal fold thickness, 1-year body weight and testicular palpation were used to predict unsuitable bulls for A.I. Non-return rate was used as a measure of fertility. Scrotal fold thickness and 1-year weight had no significant correlation with fertility or semen quality. Scrotal circumference had a significant positive correlation with fertility. Tonometer ratio had a significant negative correlation with fertility. Testicular palpation was the best basis for predicting bulls with poor semen quality in this study. Twelve bulls were recorded as having testicles of different sizes, 1 testicle being more than 20% bigger than the other. Only 2 of these 12 bulls produced semen of acceptable quality. One of these 2 bulls was, after slaughter, diagnosed as having a hereditary testicle disease. Friesians were shown to have significantly higher fertility than Ayshires. PMID- 1598855 TI - Effect of sodium nitrite and sodium chloride on growth of lactic acid bacteria. AB - The effect of NaNO2 and NaCl on the growth of 24 lactic acid bacteria strains isolated from vacuum-packed cooked ring sausages were examined by analyzing different growth parameters with Bioscreen. NaNO2 had a very limited effect on the growth of lactic acid bacteria at 50 and 100 mg/l but at 400 mg/l a more pronounced inhibitory effect was found. Bacterial growth was enhanced by 1-2% (w/v) of added NaCl, while NaCl concentrations above 3% (w/v) had a clear inhibitory effect. Leuconostoc isolates seemed to be more sensitive to sodium nitrite and sodium chloride than homofermentative lactobacilli strains. Among homofermentative lactobacilli, the strains resembling Lactobacillus curvatus were more sensitive to NaCl than those resembling Lactobacillus sake. PMID- 1598856 TI - Extraglomerular lesions in kidneys of mink with encephalitozoonosis. AB - Extraglomerular renal lesions were studied by light and electron microscopy in 13 farmed mink which showed cataractous eyes associated with spontaneous encephalitozoonosis. The extraglomerular renal lesions consisted of multiple renal cysts, multifocal-to-coalescing interstitial nephritis and vasculitis. Tubular cysts of varying size were present in the corticomedullary junction and medulla. The inflammatory infiltrates were composed mostly of lymphocytes and plasma cells and usually accompanied an interstitial fibrosis. Vasculitis, perivasculitis and sclerotic arteries were frequently seen. PMID- 1598857 TI - An epidemic of sylvatic rabies in Finland--descriptive epidemiology and results of oral vaccination. AB - When rabies reappeared in Finland in April 1988, the country had been rabies free since 1959. Soon a picture of sylvatic rabies become evident, its main vector and victim being the raccoon dog (Nyctereutes procyonoides). Between 8 April 1988 and 16 February 1989, 66 virologically verified cases were recorded (48 raccoon dogs, 12 red foxes, 2 badgers, 2 cats, 1 dog and 1 dairy bull) in an area estimated at 1700 km2 in south-eastern Finland. The greatest distance between recorded cases was 67 km. A positive reaction with monoclonal antibody p-41 indicated that the virus was an arctic-type strain. A field trial on oral immunization of small predators was initiated in September 1988 using Tubingen fox baits according to the Bavarian model of bait distribution. Each bait contained 5*10(7) TCID50/ml modified live rabies virus (SAD-B19). The 6 months' surveillance indicate a seroconversion rate of 72% (N = 126) in the raccoon dog population, 67% (N = 56) in the red foxes and 13% (N = 16) in the badgers, when titers greater than or equal to 1.0 IU/ml are considered seropositive. In the whole follow-up period, no statistically significant difference could be detected between the raccoon dogs and red foxes in the rate of seroconversion or in the uptake of tetracycline from the baits. Notably high antibody levels were recorded in both raccoon dogs and red foxes within 4-5 months after vaccination. Of the seropositive animals, the proportion of animals with titers 3.0 IU/ml or greater was higher in raccoon dogs (73%) than in red foxes (51%) (x2 = 5.29, p less than 0.05). The trial shows that raccoon dogs can be immunized against rabies in the field with vaccine baits originally developed for controlling sylvatic rabies in foxes. PMID- 1598858 TI - Some factors causing mortality among female minks during the puerperium and lactation periods. AB - The purpose of this study, in which the farm was used as the statistical unit, was to find factors affecting mink mortality under farm conditions. Mortality was hypothesised to be affected by factors including, among others, variables describing the amount (level) and variation in composition and quality of the feed. Other explanatory variables applied in the study included farm size and age. Factor analyses were performed for variables of feed composition and quality in order to condense the variable information and to facilitate the selection of explanatory variables. This report presents a preliminary regression model for female mink mortality factors describing feed level and variation, and farm size, as explanatory variables. The regression model emphasized among other factors the importance of a constant albumin quality and a constant energy level. PMID- 1598859 TI - Long term ECG recording with Holter monitoring in clinically healthy horses. AB - The electrocardiogram of 9 horses was continuously recorded for 24 h with Holter monitoring to examine the variations in heart rate and rhythm during daily routine procedures and at night. Three horses had transient sinus bradycardia, and 3 had periods of sinus tachycardia. Heart blocks were detected in 3 horses, and all horses had periods of sinus arrhythmia. These changes in the heart rate and rhythm were apparently caused by variations in autonomic nervous system tone and they are probably "normal" findings in resting, undisturbed horses. Ventricular premature depolarisations were not observed in any horse, but some single supraventricular premature contractions were detected. There was preliminary evidence that in order to register the real resting heart rate and rhythm of a horse the ECG should be recorded over a long period, and also at night and without the presence of the investigator. PMID- 1598860 TI - Comparison of neurologic responses to the use of medetomidine as a sole agent or preanesthetic in laboratory beagles. AB - Different dose regimens of medetomidine (a potent alpha 2-adrenergic agonist), adding up to a combined dose of 80 micrograms/kg, were administered to laboratory beagles to determine physiologic responses including neurologic. The study was intended to determine EEG responses where sufficient sedative and analgesic effects are reached with medetomidine and in contrast its effects when used with ketamine or halothane. Cardiopulmonary responses were very similar in each dose regimen, showing the characteristic properties of single doses of 80 micrograms/kg of medetomidine. Effective sedative and analgesic duration seemed to be a function of when the largest dose was administered. Adequate additional sedative and analgesic could be gained from injections at doses of half of the initial one. The potent sedative and analgesic effects of medetomidine confirmed by neurologic evaluation supports its potential use as a premedication to general anesthesia in dogs. In this study, 2 different doses of medetomidine were also tested as premedication to both ketamine HCI and halothane anesthesia. Neorologic responses were determined at the same time cardiopulmonary parameters, anesthetic quality, and dose requirements were recorded. Medetomidine was found to have favorable qualities in conjunction with these anesthetics. Cardiopulmonary parameters remained satisfactory in both groups as preanesthetic medication prior to halothane, but no additional benefits could be seen from doses of 40 micrograms/kg medetomidine compared to 20 micrograms/kg, except a significant 30% reduction in halothane requirement. The positive chronotropic and inotropic properties of ketamine restored the medetomidine-induced bradycardia and produced a short anesthetic period of 15 to 30 min depending on the dose of medetomidine. The quality of anesthesia was better when 40 micrograms/kg medetomidine was used, but recovery was quicker with 20 micrograms/kg medetomidine. Medetomidine significantly reduced cerebral activity as demonstrated by recordings of total amplitude and frequency evaluation of the EEG with compressed spectral analysis. This analytical method was effective in confirming clinical signs of sedation, analgesia, and anesthesia in canine subjects. PMID- 1598861 TI - Computerized and subjective assessments of post-thaw motility of semen from Finnish Ayrshire AI bulls in relation to non-return rates. AB - A semen analyser (Lazymot), was used to evaluate post-thaw motilities in 296 batches of semen from 74 Ayrshire bulls used for artificial insemination (AI). Motility was also assessed subjectively. A significant correlation was observed between assessments of motility using the Lazymot analyser and the subjective assessments. There was no correlation between post-thaw motility assessments and non-return rates in relation to the batches examined, which met Finnish criteria for use in AI. This suggests that criteria for post-thaw semen motility should not be increased beyond the present requirement for 40% motile spermatozoa. PMID- 1598862 TI - Lactic acid bacteria for mink. Colonization and persistence of Enterococcus faecium Cernelle 68 in the digestive tract of mink. AB - A method was developed to follow a lactic acid bacterial strain, Enterococcus faecium Cernelle 68, with respect to adhesion, multiplication, colonization, and persistence in the digestive tract of mink. Also the spread of the strain in the cage was examined. When adding 5 x 10(9) c.f.u. of a rifampicin resistant mutant per kg feed, high viable counts were registered throughout the digestive tract, apart from the oesophagus. Counts were increasing in the aboral direction, suggesting some multiplication in the intestine. It was possible to detect the strain in the intestinal tract 4 days after discontinuation of administration. Neither culture nor scanning electron microscopy gave evidence to suggest that E. faecium Cernelle 68 adhered to the mucosa. The spread of the E. faecium strain was observed in the environment. Counts of E. coli, lactobacilli, staphylococci, and clostridia were low, and none of these bacteria were constant findings. PMID- 1598863 TI - Mechanism of exercise-induced hypotension in coronary artery disease. AB - Hypotension during exercise testing has been considered a marker of extensive coronary artery disease (CAD) and poor prognosis. The mechanism of hypotension was examined in 25 CAD patients who developed hypotension during treadmill exercise testing (mean decrease in systolic blood pressure [BP] 33 +/- 13 mm Hg) (group 1) and was compared with the results of 25 CAD patients who had a normal systolic BP response to exercise (mean increase 53 +/- 15 mm Hg) (group 2). The 2 groups were comparable in age, sex, extent of CAD, previous myocardial infarction, left ventricular ejection fraction, history of hypertension and cardiac medications. Exercise heart rate (121 +/- 23 vs 133 +/- 25 beats/min; p = not significant [NS]) and duration (6 +/- 2 vs 7 +/- 3 minutes; p = NS) were comparable. ST-segment depression occurred in 44% of patients in group 1 and in 52% in group 2 (p = NS), and angina during exercise occurred in 60% of both groups. Single-photon emission computed tomographic thallium images were abnormal in 24 patients (96%) in group 1 and in 20 patients (80%) in group 2 (p = NS). Percent thallium abnormality was 19 +/- 12% in group 1, and 18 +/- 14% in group 2 (p = NS), and the severity of thallium abnormality was 710 +/- 510 in group 1, and 510 +/- 500 in group 2 (p = NS). Ischemia involving the inferior/posterior segments was seen in 68% of patients in group 1 and in 60% in group 2 (p = NS). Increased lung thallium uptake was seen in 48% of both groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598864 TI - Frequency and predictors of left ventricular segmental dysfunction in patients with recent rest angina. AB - The relation between coronary artery lesion morphology and associated segmental left ventricular (LV) dysfunction in patients with unstable angina is unclear. Fifty-two patients with angina occurring at rest who underwent cardiac catheterization within 3 days of the last episode of pain and had no enzymatic evidence for myocardial necrosis were evaluated. Coronary artery narrowings deemed responsible for the ischemic episodes were analyzed with regard to the artery involved, maximal diameter of the narrowing, presence of thrombus, and complex appearance. Time to catheterization, age, sex and electrocardiographic evidence of ischemia were also noted. Segmental LV dysfunction in the territory supplied by the "culprit lesion" was present in 58% of patients. It occurred significantly more often with lesion location in the left anterior descending coronary artery, and was less frequent with lesions in the left circumflex and ramus coronary arteries. Ischemic electrocardiographic changes were more sensitive in predicting LV dysfunction with culprit lesion location in the left anterior descending or right coronary artery. LV dysfunction could not be predicted by any other parameter analyzed. It is concluded that postischemic LV dysfunction occurs frequently in rest angina, especially when the severest narrowing is in the left anterior descending coronary artery. PMID- 1598865 TI - Immediate and follow-up results of the conservative coronary angioplasty strategy for unstable angina pectoris. AB - To assess the results of a conservative coronary angioplasty strategy in unstable angina pectoris, the records of 1,421 consecutive patients without previous myocardial infarction undergoing a first percutaneous transluminal coronary angioplasty (PTCA) between 1986 and 1990 were reviewed. Of these patients, 631 had unstable and 790 had stable angina pectoris. Only after an intense effort to medically control symptoms, the unstable patients underwent PTCA at an average of 15.4 days (range 1 to 76) after hospital admission. Primary clinical success was achieved in 91.7% of patients with unstable and in 94.4% of those with stable angina pectoris (p = not significant). In-hospital mortality rates were 0.3 and 0.1%, respectively (p = not significant). Nonfatal in-hospital event rates for acute myocardial infarction, cerebrovascular accident and coronary bypass surgery were only slightly higher in patients with unstable angina pectoris; however, the difference from the stable group was significant when all events were combined (9 vs 5.9%; p less than 0.04). During 6-month follow-up, no significant difference in adverse events was found between the groups. The respective rates for the unstable and stable groups were 0.4 and 0.2% for death, 5.5 and 5.1% for major nonfatal events, and 17.7 and 20.1% for repeat PTCA. These results suggest that use of a conservative PTCA strategy in the treatment of patients with unstable angina pectoris results in favorable and similar immediate and 6-month outcomes compared with those in patients with stable angina pectoris. PMID- 1598866 TI - Echocardiographic algorithms for admission and predischarge prediction of mortality in acute myocardial infarction. AB - To develop improved prognostic algorithms for routine bedside use in acute myocardial infarction (AMI), the prognostic value concerning 2- and 12-month mortality of an early (within 72 hours after AMI) resting echocardiogram was defined in 201 consecutive patients. The relation between (1) the clinical variables (age, sex, prior and repeat AMI, arrhythmias, cardiac arrest, early [less than 72 hours after AMI] and late heart failure, early and maximal in hospital Killip class, and maximal creatine kinase-MB isoenzyme), (2) early myocardial performance by echocardiography, and (3) mortality was characterized by Kaplan-Meier survival curves and receiver-operating characteristic curves based on Cox regression model. Only age and clinical heart failure in terms of the maximal in-hospital Killip class had independent predictive value of death (p less than 0.05) when an early echocardiographic estimate of left ventricular ejection fraction (LVEF) was included in the multivariate statistical models. The following 2 optimized algorithms for admission and predischarge calculation of risk of mortality at 2 and 12 months were developed based on the Cox model, using combinations of age, maximal Killip class and early echocardiographic LVEF: mortality at 2 months = 1 - exp - [0.051 x exp [0.044 x (age -60) - (0.117 x (LVEF - 40)]]; and mortality at 1 year = 1 - exp - [0.101 x exp [0.408 x (maxKillip - 1) - (0.061 x (LVEF - 40)]]. Discriminative power for prediction of mortality of the predischarge algorithm in an independent population of 195 patients 5 days after AMI compared favorably with that obtained in the original population, confirming the validity of the proposed method of prognostication. PMID- 1598867 TI - Electrocardiographic criteria for diagnosis of acute myocardial infarction in childhood. AB - Myocardial infarction (MI), a common occurrence in adults, is generally considered to be rare in children. Electrocardiographic criteria for diagnosis of MI in adults are well known and accepted, but no general criteria exist for children. We report 37 autopsy-proved cases of transmural MI and electrocardiographic evidence of MI in 30 of these cases. A variety of conditions previously reported to produce "pseudo-infarction" are included in these cases of MI, including myocarditis, hypertrophic cardiomyopathy, and the cardiomyopathy of Duchenne's muscular dystrophy. Compilation of the electrocardiographic data in all patients allowed for the development of criteria for this diagnosis of MI in childhood, and include wide Q waves (greater than 35 ms) with or without Q-wave notching, ST-segment elevation (greater than 2 mm), and prolonged QT interval corrected for heart rate (QTc greater than 440 ms) with accompanying Q-wave abnormalities. With use of these electrocardiographic criteria, an additional 3 patients were subsequently diagnosed prospectively with MI and confirmed on autopsy. Pathologic evaluation confirmed the location of infarction predicted by the electrocardiograms in all 3 cases. PMID- 1598868 TI - Frequency of coronary artery disease and left ventricle dysfunction in cocaine users. AB - To evaluate the spectrum of coronary artery disease (CAD) in cocaine users, coronary angiograms obtained from 33 patients (26 men [79%] and 7 women [21%], mean age 37 years) with history of cocaine use and cardiac symptoms were retrospectively reviewed. Clinical indications for coronary angiograms included chest pain (n = 28), congestive failure (n = 4) and complete heart block (n = 1). Coronary angiograms were reviewed independently by 2 angiographers unaware of patient's clinical status. Thirteen patients (40%) had normal coronary angiograms, and 20 (60%) had CAD; 7 (21%) had mild CAD (less than or equal to 70% diameter stenosis), and 13 (40%) had significant CAD (greater than 70% diameter stenosis). Of 13 patients with significant CAD, 7 had 1-vessel, 4 had 2-vessel and 2 had 3-vessel CAD. There was enzymatic evidence of myocardial infarction in 12 of 33 patients (36%); all 12 had CAD (10 with significant and 2 with mild CAD). Mean age and number of risk factors (serum total cholesterol, cigarette smoking, systemic hypertension, diabetes mellitus, family history of CAD, and obesity) in patients with CAD (mild or significant) and with normal coronary angiograms were not statistically different. Left ventricular ejection fraction was normal in 15 patients (45%) and depressed in 18 (55%). All patients with CAD and low ejection fractions (n = 12) had regional wall motion abnormalities, whereas all those with normal coronary arteries and low ejection fraction (n = 6) had global hypokinesia. PMID- 1598869 TI - Preoperative coronary artery disease risk stratification based on dipyridamole imaging and a simple three-step, three-segment model for patients undergoing noncardiac vascular surgery or major general surgery. AB - A 3-step, 3-segment scintigraphic model was developed to improve the accuracy of dipyridamole-thallium imaging for preoperative cardiac risk assessment and to simplify the prognostic interpretation of the images. The model was developed in a pilot study of 60 patients and validated in a group of 355 patients referred for vascular and major general surgery. Study end points included myocardial infarction and cardiac death. Step 1: The postoperative cardiac event rate was 1.3% in 225 patients with normal anterior, inferio- and posterolateral segment perfusion and without transient left ventricular dipyridamole-induced cavitary dilation. Step 2: The physiologic rationale for step 2 consists of identifying patients who are most likely to have left main, 3-vessel or high-risk 2-vessel coronary artery disease or a significant amount of jeopardized myocardium in the territory of a critical coronary stenosis. Of 29 patients with either reversible defects of all 3 segments, transient cavitary dilation, or at least 1 severe grade 3/3 reversible defect, 52% (15 of 29) sustained a postoperative cardiac event. Step 3: The remaining 101 patients were stratified according to age greater than 70 years (p = 0.01), presence of diabetes (p = 0.0004) and the number of segments displaying reversible defects (1 or 2) with cardiac event rates ranging from 5 to 36%. The 3-step, 3-segment model is a useful alternative to the conventional interpretation of dipyridamole myocardial perfusion images for the purpose of quick and efficient preoperative risk stratification based on the rationale of correlating surgical risk with the amount of potentially ischemic myocardium.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598870 TI - Anaerobic threshold detection in patients with congestive heart failure. AB - Anaerobic threshold measurements determined either invasively by analysis of arterial lactate concentration (lactate threshold) or noninvasively by respiratory gas exchange analysis (ventilatory threshold) were compared in patients with chronic congestive heart failure. Sixteen patients performed symptom-limited maximal exercise on a bicycle ergometer using a continuous ramp protocol with measurement of arterial lactate concentration at 1 minute intervals, and continuous breath-by-breath analysis of respiratory gas exchange. A specific lactate threshold point was detected in only 7 patients. These 7 patients had significantly greater peak oxygen uptake than did the 9 in whom no specific lactate threshold point was detected (15.9 +/- 1.0 vs 10.5 +/- 0.5 ml/kg/min; p less than 0.05). Ventilatory threshold significantly correlated with lactate threshold in these 7 patients. In the remaining 9 patients, neither lactate nor ventilatory threshold could be reliably determined with methods used in the present study. PMID- 1598871 TI - Left ventricular dysfunction due to atrial fibrillation in patients initially believed to have idiopathic dilated cardiomyopathy. AB - Ten patients aged 22 to 80 years (median 57) with severe left ventricular (LV) dysfunction and atrial fibrillation (AF) with rapid ventricular response were evaluated after therapy. Because most patients were unaware of their arrhythmia, duration was usually unknown. All patients had heart failure symptoms; 9 presented with New York Heart Association class III or IV disability, and 1 with class II disability. Initial LV ejection fraction ranged from 12 to 30% (median 25). No patient had symptomatic coronary artery disease (4 underwent angiography). Myocarditis and infiltrative processes were excluded by biopsy in 5 patients. All patients were considered initially to have idiopathic dilated cardiomyopathy with secondary AF. Ventricular rate was controlled in all patients, with sinus rhythm restored in 5. At follow-up (median 30 months, range 3 to 56), all patients were asymptomatic. LV ejection fraction after treatment ranged from 40 to 64% (median 52). It is concluded that in some patients initially considered to have idiopathic dilated cardiomyopathy, AF with rapid ventricular response may be the primary cause rather than the consequence of severe LV dysfunction. LV dysfunction may be completely reversible with ventricular rate control. PMID- 1598872 TI - Myocardial adenine nucleotide concentrations and myocardial norepinephrine content in patients with heart failure secondary to idiopathic dilated or ischemic cardiomyopathy. AB - It has been suggested that chronically reduced myocardial adenosine triphosphate (ATP) content causes contractile dysfunction in dilated cardiomyopathy. Because total adenine nucleotides (ATP, adenosine diphosphate and monophosphate) may reflect chronic changes in energy metabolism better than may ATP alone, myocardial ATP, and adenosine diphosphate and monophosphate were determined in endomyocardial biopsy specimens from 19 patients with dilated cardiomyopathy, and decreased left (30 +/- 2%) and right (34 +/- 3%) ventricular ejection fractions, and from 11 patients with ischemic cardiomyopathy (left ventricular ejection fraction 38 +/- 3%), and compared with those from 28 normal control subjects (ejection fraction greater than 55%) to assess myocardial energy metabolism in heart failure. Myocardial norepinephrine was measured simultaneously in the same biopsy specimens to assess if the myocardium studied for adenine nucleotide content was metabolically altered. Myocardial total adenine nucleotides as well as ATP levels in 19 patients with dilated cardiomyopathy (39 +/- 3 and 23 +/- 3 nmol/mg of noncollagen protein, respectively) were unchanged in comparison with those of control subjects (37 +/- 4 and 23 +/- 3, respectively); patients with ischemic cardiomyopathy were not significantly different (30 +/- 3 and 19 +/- 3, respectively). Myocardial norepinephrine in the same biopsy specimens from patients with dilated (5.8 +/- 1.1 pg/micrograms of noncollagen protein) or ischemic (5.7 +/- 1.3) cardiomyopathy was significantly decreased compared with that of normal control subjects (12 +/- 1.1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598873 TI - Use of limb movement sensors as indicators of the level of everyday physical activity in chronic congestive heart failure. AB - The level of everyday physical activity of patients with chronic congestive heart failure (CHF) may be an important reflection of their quality of life. Everyday physical activity is difficult to measure objectively, and may not relate to exercise capacity determined by laboratory exercise testing. A light-weight sensor worn on the wrist or ankle, which provides a cumulative record of limb movement, was evaluated. The sensor counted reliably when tested in a laboratory rig and during treadmill exercise. In 20 young normal subjects, hourly movement scores showed the expected diurnal rhythm. Twenty-four-hour movement scores in 30 patients with stable CHF were lower than in 20 age-matched control subjects (p less than 0.005). Movement scores in CHF correlated with a standard questionnaire scale assessing everyday physical activity (R = +0.72, p less than 0.001). Consecutive daily scores varied widely, but wrist and ankle scores were correlated (R greater than +0.7, p less than 0.05 in each subject), suggesting true day-to-day differences in activity rather than variability in the recording method. Recording for 5 to 6 consecutive days provides a reliable estimate of mean 24-hour movement score for a subject, and mean 24-hour scores were reproducible when subjects were retested after 8 weeks. There was a weak correlation between movement scores and exercise capacity as measured by peak oxygen consumption during maximal treadmill exercise (R = +0.42, p = 0.01). Quality-of-life score correlated with movement scores (R = +0.53, p less than 0.002) but not with peak oxygen consumption (R = +0.36; p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598874 TI - Effect of quinapril on blood pressure and heart rate in congestive heart failure. AB - The effect of quinapril on blood pressure (BP), heart rate (HR) and their variabilities in 12 patients with severe congestive heart failure (New York Heart Association class III and IV) was assessed using ambulatory electrocardiographic and intraarterial monitoring. Mean +/- standard deviation daytime BP was 122/75 +/- 20/15 mm Hg at baseline and 113/70 +/- 13/16 mm Hg after 16 weeks of therapy with quinapril (p greater than 0.05 for systolic and diastolic BP); mean nighttime BP was 114/69 +/- 19/14 mm Hg at baseline and 107/69 +/- 15/14 mm Hg with quinapril (p greater than 0.05 for systolic and diastolic BP). Mean daytime HR was unchanged but nighttime HR was reduced from 77 +/- 11 to 71 +/- 10 beats/min, p = 0.02. HR variability (difference between the 75th and 25th percentiles of the frequency distribution of RR intervals) increased from 91 +/- 34 to 134 +/- 47 ms, p = 0.008. The variability of successive differences between RR intervals also increased significantly (75th to 25th percentile = 17 +/- 4 ms at baseline and 31 +/- 26 ms with quinapril, p = 0.02). Long-term quinapril caused clinically unimportant decreases in BP in patients with severe congestive heart failure. An increase in vagal activity caused by the reduction in circulating angiotensin II may account for the effect of converting enzyme inhibition on HR and its variability. PMID- 1598875 TI - Effectiveness of preload reserve as a determinant of clinical status in patients with left ventricular systolic dysfunction. The SOLVD Investigators. AB - The hemodynamic determinants of clinical status in patients with left ventricular (LV) systolic dysfunction have not been established. In the present study, preload reserve--LV distension during exercise--was related to clinical status, and the effect of acute angiotensin-converting enzyme inhibition was examined in 97 patients with ejection fraction less than or equal to 0.35 enrolled in the trial, Studies of Left Ventricular Dysfunction (SOLVD). Sixty-one asymptomatic patients (group I) were compared with 36 patients with symptomatic heart failure (group II). Radionuclide LV volumes were measured at rest and during maximal cycle exercise. Group II patients had higher resting heart rates, end-diastolic and end-systolic volumes, and lower ejection fractions (all p less than 0.005). During exercise, only patients in group I had increased stroke volume (from 35 +/ 8 to 39 +/- 11 ml/m2 [mean +/- SD; p less than 0.0005]) due to an increase in end-diastolic volume (from 119 +/- 29 to 126 +/- 29 ml/m2 [p less than 0.0005]), contributing to a greater increase in LV minute output (p less than 0.0001, group I vs group II). After administration of intravenous enalapril (1.25 mg), LV end diastolic volume response to exercise was augmented in group II (rest, 140 +/- 42; exercise, 148 +/- 43 ml/m2; p less than 0.0005) and LV output response increased slightly (p less than 0.05). Thus, in patients with asymptomatic systolic dysfunction, recruitment of preload during exercise is responsible for maintaining a stroke volume contribution to the cardiac output response.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598876 TI - Endothelial function in chronic congestive heart failure. AB - There is evidence that the endothelium plays an important role in the control of human vascular tone by releasing endothelium-derived nitric oxide. The hypothesis that an impairment of this mechanism is involved in the increased peripheral vasoconstriction of patients with chronic congestive heart failure (CHF) was tested. Acetylcholine and N-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis from L-arginine, were infused in the brachial artery of healthy volunteer subjects (controls) and patients with severe CHF. The radial artery diameter was determined by a high-precision A-mode ultrasound device, using a 10 MHz probe. Forearm blood flow was calculated from vessel diameter and blood flow velocity measured simultaneously by Doppler. The blood flow response to acetylcholine was blunted in patients with CHF compared with that in control subjects. In contrast, the decrease in blood flow induced by L-NMMA was exaggerated in CHF, and the blood flow response to nitroglycerin was preserved. The changes in radial artery diameter induced by acetylcholine and L-NMMA were not significant in control subjects and CHF patients, but dilation of the radial artery by nitroglycerin was significantly reduced in CHF. The results demonstrate an impaired endothelium-dependent dilation of forearm resistance vessels in CHF, suggesting a reduced release of nitric oxide on stimulation. In contrast, the basal release of nitric oxide from endothelium of forearm resistance vessels is preserved or may even be enhanced, and may play an important compensatory role in chronic CHF by antagonizing neurohumoral vasoconstrictor forces in CHF. PMID- 1598877 TI - Long-term (9 to 33 months) echocardiographic follow-up after successful percutaneous mitral commissurotomy. AB - Late results after successful percutaneous mitral commissurotomy were assessed by prospective clinical and echocardiographic follow-up. Fifty-seven patients were followed for a mean of 19 +/- 6 months (range 9 to 33) after the procedure. Mitral valve area (measured by Doppler half-time method) increased from 1.0 +/- 0.2 to 2.2 +/- 0.5 cm2 immediately after commissurotomy, and then decreased to 1.9 +/- 0.5 cm2 at follow-up (p less than 0.05), whereas gradient did not change after its immediate postcommissurotomy reduction. Echocardiographic restenosis (mitral valve area less than or equal to 1.5 cm2 with greater than 50% reduction of initial gain) was seen in 12 of 57 patients (21%). Atrial shunting, detected by transthoracic color Doppler in 61% of patients immediately after the procedure (color flow jet through atrial septum), persisted in 30% at follow-up. Restenosis by univariate analysis correlated with age, smaller valve area after the procedure, and higher echocardiographic score. Multivariate analysis identified leaflet mobility and calcifications as the components of a score that was predictive for restenosis. Magnitude of shunt (pulmonary-to-systemic flow ratio greater than 1.5), use of a Bifoil balloon (2 balloons on 1 shaft), and smaller valve area after the procedure were predictors by multivariate analysis of the persistence of atrial shunting. Clinical improvement persisted at long-term follow-up (mean New York Heart Association class 1.6 +/- 0.6 vs 2.6 +/- 0.6 before commissurotomy). Improvement of greater than or equal to 1 functional class was seen in 75% of patients (80% of those without and 58% of those with restenosis); patients with a shunt did not differ from the entire group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598878 TI - Methodologic issues in clinical evaluation of stenosis severity in adults undergoing aortic or mitral balloon valvuloplasty. The NHLBI Balloon Valvuloplasty Registry. AB - Although both catheterization and Doppler measures of valvular stenosis severity have been validated, each has specific advantages and limitations, particularly in the setting of balloon valvuloplasty. Invasive valve area and mean pressure gradient recorded immediately before and after aortic (n = 589) or mitral (n = 608) catheter balloon valvuloplasty were compared with Doppler valve area and mean pressure gradient recorded less than 30 days before and 24 to 72 hours after the procedure. For aortic stenosis, Doppler valve area ranged from 0.1 to 1.4 cm2 before and 0.2 to 2.3 cm2 after catheter balloon valvuloplasty. Doppler and invasive aortic valve areas differed by less than or equal to 0.5 cm2 in 99% and by less than 0.2 cm2 in 92% of patients. Linear correlation was higher before versus after catheter balloon valvuloplasty, for both valve area (r = 0.49 vs r = 0.35, p = 0.01) and mean pressure gradient (r = 0.64 vs r = 0.50, p = 0.01). Group mean invasive valve area was slightly smaller before (0.50 vs 0.59 cm2, p less than 0.0001) but was not different after (0.80 vs 0.78 cm2, p = 0.16) catheter balloon valvuloplasty. Variables affecting the valve area differences were cardiac output, aortic regurgitation, heart rate and blood pressure. Mean pressure gradient differences were related to echo quality, blood pressure and mitral regurgitation. For mitral stenosis, 2-dimensional echocardiographic valve area ranged from 0.4 to 2.8 cm2 before and 0.7 to 3.8 cm2 after catheter balloon valvuloplasty. Two-dimensional echocardiography and invasive mitral valve areas differed by less than or equal to 0.5 cm2 in 96% and by less than 0.2 cm2 in 81% of cases. Linear correlation was not different before versus after catheter balloon valvuloplasty for two-dimensional echocardiographic valve area (r = 0.40 vs 0.36), pressure halftime valve area (r = 0.31 vs 0.32) or mean pressure gradient (r = 0.55 vs r = 0.46). Group mean 2-dimensional echocardiography and pressure halftime valve areas were larger than invasive valve areas before (1.09 vs 1.02 cm2, p = 0.001) and smaller after (1.71 vs 2.02 cm2, p less than 0.0001) catheter balloon valvuloplasty. Important variables affecting the differences were mitral regurgitation, interatrial shunt, cardiac output and heart rate. Nonsimultaneous studies, differing volume flow measurements, and the underlying accuracy of each technique largely account for discrepancies between these methods. The clinical use of each will depend on its ability to predict long-term patient outcome. PMID- 1598879 TI - Predictors of exercise benefit after operative relief of left ventricular outflow obstruction by the myotomy-myectomy procedure in hypertrophic cardiomyopathy. AB - To determine predictors of exercise benefit in patients with hypertrophic cardiomyopathy after operative relief of left ventricular (LV) outflow tract obstruction, 30 patients underwent catheterization and exercise testing before and 6 months after operation, and hemodynamic measurements were obtained. The increase in maximal oxygen consumption (VO2max) during treadmill exercise testing was chosen as an index of exercise benefit. Univariate analysis showed a significant positive correlation of operative change in VO2max with preoperative LV end-diastolic and pulmonary arterial wedge pressures, operative change in exercise duration, and operative reductions in LV end-diastolic and pulmonary arterial wedge pressures and resting LV outflow tract gradient, and a significant negative correlation with preoperative VO2max and percent predicted VO2max. Multivariate analysis by stepwise linear regression of only significant univariate variables selected only preoperative percent predicted VO2max, and operative reduction in LV end-diastolic pressure and resting LV outflow tract gradient as significant predictors of postoperative change in VO2max. Stepwise regression analysis, applied only to preoperative exercise and catheterization hemodynamic variables, selected only preoperative percent predicted VO2max and preoperative LV end-diastolic pressure as predictors of improvement in exercise capacity. Thus, patients with obstructive hypertrophic cardiomyopathy, after failing medical therapy, are most likely to demonstrate improvement in exercise capacity if preoperative exercise testing demonstrates limited exercise capacity and if surgery achieves reduction in elevated resting LV outflow tract gradients and LV filling pressures. PMID- 1598880 TI - Doppler echocardiographic assessment of the pressure gradient during bicycle ergometry in hypertrophic cardiomyopathy. AB - To assess the behavior of the subvalvular pressure gradient under physical exercise, 13 patients with obstructive hypertrophic cardiomyopathy were examined during upright bicycle ergometry by means of Doppler echocardiography. Additionally, right-sided cardiac catheterization was performed within 7 days. In 10 patients adequate Doppler tracings could be obtained during exercise. The Doppler-derived systolic pressure gradient increased from 75 +/- 24 to 140 +/- 42 mm Hg (p less than 0.0005). This was associated with an increase in the duration of the systolic mitral-septal contact from 59 +/- 21 to 136 +/- 28 ms (p less than 0.0005). Correlation between the pressure gradient and the duration of mitral-septal contact at rest and during exercise was good (r = 0.86), whereas correlation between the resting and exercise pressure gradient (r = 0.34) did not reach statistical significance. The increase in stroke volume during exercise, from 90 +/- 18 to 95 +/- 24 ml, was significant (p less than 0.05) but minimal. Therefore, only a moderate increase in systolic flow, from 205 +/- 54 to 268 +/- 78 ml/s (p less than 0.0005), was observed. Outflow tract resistance, defined as the ratio of the pressure gradient to systolic flow, increased from 0.38 +/- 0.11 to 0.57 +/- 0.24 mm Hg.s/ml (p less than 0.01). Thus, in a selected group of patients with hypertrophic cardiomyopathy a substantial increase in the maximal pressure gradient during upright bicycle ergometry was demonstrated in most patients. Exercise Doppler echocardiography may be valuable to assess the hemodynamic significance of obstruction in individual patients in a physiologic setting and has a potential to monitor the effect of therapeutic interventions. PMID- 1598881 TI - Impairment of left ventricular diastolic function in systemic lupus erythematosus. AB - Left ventricular (LV) diastolic performance was evaluated with pulsed-wave Doppler echocardiography in a cross-sectional population of patients with systemic lupus erythematosus (SLE) in search of subclinical myocardial involvement. Such involvement is reported to occur infrequently, despite pathohistologic evidence of myocarditis in up to 70% of patients with SLE. Thirty five consecutive patients with SLE were evaluated, 14 with active and 21 with inactive disease, and were compared with 30 age-matched healthy control subjects. Twenty-six patients were restudied at 7 months. All had normal LV systolic function, normal pericardial and valvular structures, and no significant valvular regurgitation on Doppler echocardiography. In SLE patients with active disease, indexes of LV diastolic function differed significantly from the inactive group and from control subjects, with marked prolongation of isovolumic relaxation time (104 +/- 18 vs 74 +/- 13 ms, p = 0.0001), as well as reduced peak early diastolic filling velocity (E) (0.69 +/- 0.19 vs 0.83 +/- 0.17 ms, p = 0.01), reduced ratio of early to late diastolic flow velocity (E/A) (1.15 +/- 0.53 vs 1.47 +/- 0.35, p = 0.02), and prolonged mitral pressure halftime (74 +/- 14 vs 65 +/- 8 ms p = 0.01). Similar significant differences were found between the active and inactive SLE patient groups. SLE patients with inactive disease differed from control subjects in only mild prolongation of mitral pressure halftime. Abnormal prolongation of isovolumic relaxation (greater than 100 ms) was found to be the most useful marker of diastolic impairment, being present in 64% of SLE patients with active disease and in 14% of patients with inactive disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598882 TI - Observations of coronary flow augmentation and balloon function during intraaortic balloon counterpulsation using transesophageal echocardiography. AB - The intraaortic balloon pump has been shown to decrease myocardial oxygen demand by afterload reduction, while increasing myocardial oxygen supply by diastolic augmentation of coronary blood flow. This diastolic augmentation of coronary flow has been demonstrated experimentally with invasive methods. Noninvasively, transesophageal echocardiography has demonstrated efficacy in enabling visualization of the proximal left coronary artery and in recording coronary blood flow velocity. To assess the potential of this technique in demonstrating quantitatively the increase in coronary flow during counterpulsation, 6 patients were studied during intermittent balloon pumping. Peak diastolic coronary blood flow velocity increased by a mean of 117% (range 62 to 287) during balloon inflation (p = 0.002). Furthermore, coronary flow velocity integral increased by a mean of 87% (range 43 to 176; p = 0.003). Problems associated with intraaortic balloon pumping were discovered by transesophageal echocardiography in 4 patients (incorrect balloon placement, damage to the aortic wall [2 patients], and premature balloon deflation time). Transesophageal echocardiography can be used in evaluating intraaortic balloon positioning within the aorta and in monitoring coronary artery flow augmentation during counterpulsation. This relatively noninvasive technique adds another dimension to the evaluation of balloon function and may help in optimizing the benefits of counterpulsation. PMID- 1598884 TI - Syndromes X: two too many. PMID- 1598883 TI - Excimer coronary laser angioplasty: it's time for a critical evaluation. PMID- 1598886 TI - Cervical face-bows: a viewpoint of a health professional. PMID- 1598885 TI - Compliment on article thoroughness and case selection. PMID- 1598887 TI - Comment on lip bumper treatment. PMID- 1598888 TI - Differential tooth movement in "uphill cases". AB - The continuing relevance of the light-wire appliance is illustrated by the treatment of three cases, with emphasis on the beneficial effect of Class II intermaxillary traction the vertical dimension in "low-angle" cases. PMID- 1598889 TI - Mixed-dentition treatment. PMID- 1598890 TI - Vertical growth of the anterior face: a new approach. AB - The mechanism of anterior vertical facial growth was studied in normal subjects between 7 and 22 years of age. This subsample (n = 60) of participants in the Nijmegen Growth Study was representative of normal variation with respect to vertical facial proportions. A negative correlation was found between the average growth rate of the upper and lower anterior facial height in boys. Boys with a relatively large facial height exhibited a higher than average growth rate of the lower anterior facial height compared with the upper facial height. In girls a similar trend was present. The individual average growth rate of the anterior upper and lower facial height maintains or accentuates the early established facial form. PMID- 1598891 TI - Analysis of soft tissue facial profile in white males. AB - Three of the integumental variables, namely, the total facial convexity, upper lip to esthetic plane, and lower lip length, showed significant measurement errors in the preadolescent boys. Large standard deviations were also found for several variables in both age groups. This suggests that a range of values, rather than means, should be used in clinical cephalometric evaluations. A table of means, standard deviations, and ranges for the variables evaluated is provided. The nasolabial and the mentolabial angles did not differ significantly between the younger and the older age groups. The total soft tissue facial convexity was noted to have a marginally significant difference between the adults and children. Other variables were significantly different between the two age groups, and indicated that the adults had a relatively straighter facial profile than the children. In addition, the upper and lower lips were more retrusive relative to the esthetic plane in adults. Sagittal proportions relating nasal depth/nose to most protrusive lip/chin to most protrusive lip were found to have a ratio of 2.1:1.0:1.2 in children and 1.8:1.0:0.3 in adults. PMID- 1598892 TI - Some vertical lineaments of lip position. AB - This study was performed to elucidate quantitatively upper lip-tooth-jaw relativity in the vertical dimension. Values for five linear dentolabial measurements were generated from male (n = 42) and female (n = 46) reference samples. In addition, three vertical skeletofacial dimensions and two vertical dental dimensions were recorded. A significant sexual dimorphism was found in the vertical lip-tooth-jaw relationship: the upper lip of the female subjects was positioned on average 1.5 mm more superiorly at maximum smile than the upper lip of the male subjects (p less than 0.01). High smile lines appeared to be a female lineament, and low smile lines appeared to be a male lineament. There was a significant sex difference in upper lip length: the male subjects exhibited a longer upper lip than the female subjects (p less than 0.001). The mean difference was 2.2 mm. A similarly significant male-female difference was seen in the skeletal maxillary height measurement: the male sample showed a 2.2 mm mean vertical maxillary increase over the female sample (p less than 0.001). Furthermore, a significant difference was found between the clinical crown height of the maxillary central incisors in the male and female subjects of comparable ages: the male group had longer central incisor crowns (p less than 0.01). PMID- 1598893 TI - Obstructive sleep apnea subtypes by cluster analysis. AB - A sample of 84 adult male patients with obstructive sleep apnea (OSA) were classified by a cluster analysis on the basis of apnea index (AI) and body mass index (BMI). Demographic, cephalometric, tongue, soft palate, and upper airway size data were evaluated for the two subgroups of OSA patients and for 18 control subjects. One OSA group consisted of 43 patients with a high AI and low BMI ratio, the other group was comprised of 41 patients with a low AI and high BMI ratio. The patients with a high AI and low BMI ratio had retruded mandibles with high mandibular plane angles and proclined lower incisors. The patients with a low AI and high BMI ratio had inferior hyoid bones and large soft palates. A multiple regression analysis was performed between AI (the dependent variable) and the other variables (independent variables) for each of the subgroups. In the patients with a high AI and low BMI ratio, a high AI was related to a large skeletal anteroposterior discrepancy, a steep mandibular plane, and an inferoanterior position of the hyoid bone. In the patients with a low AI and high BMI ratio, a high AI was related to a large tongue and a small upper airway. In both groups, BMI was the major contributor to AI. In conclusion, these two groups may represent distinct subgroups of OSA patients and provide some insight into the contribution of obesity to the pathogenesis of OSA. The patients with a high AI and low BMI ratio have a skeletal mismatch, whereas the patients with a low AI and high BMI have atypical soft tissue structures. PMID- 1598894 TI - Mandibular growth direction with conventional Class II nonextraction treatment. AB - The purposes of this study were (1) to compare the direction of mandibular growth (MGD) during treatment and retention for a group of treated Class II patients with untreated controls, and (2) to investigate the relationship between the MGD during treatment and the pretreatment skeletal structure. Pretreatment, posttreatment, and 2 years posttreatment lateral cephalograms of 26 Class II, Division 1 subjects who were treated "nonextraction" with low- or straight-pull headgears were compared with an untreated control group of 15 subjects. Mandibular growth direction was interpreted as the movement of the point gnathion relative to the S-N line when successive tracings were superimposed on the S-N line at S. On average, MGD appeared more vertical during treatment. Posttreatment MGD was generally more horizontal than that during treatment but was also extremely variable. Three of the pretreatment skeletal measures studied, especially the articular angle (SArGo), were significantly related to MGD during treatment. The inclination of the mandibular ramus is apparently an important indicator of how mandibular growth will respond to Class II treatment mechanics. PMID- 1598895 TI - Soft tissue response to mandibular advancement and genioplasty. AB - Changes in facial esthetics after orthognathic surgery should be predictable if the results are to be satisfactory. The skeletal elements are moved in a planned and controlled manner, but the soft tissue drape is not as precisely managed. This study was on 31 patients who had undergone a mandibular advancement by means of a sagittal split osteotomy, 17 of whom had also received an advancement genioplasty and 6 received a maxillary impaction. The results showed a consistent 1:1 ratio of soft to hard tissue advancement at pogonion and B point, and that predictions could be accurate in both anteroposterior and vertical directions. When a genioplasty was added to the advancement, however, the results were much less consistent. The mean ratio was 0.9:1 of soft tissue to skeletal movement at pogonion, but the average difference between hard and soft tissue movement was +/ 2.6 mm. Thus the prediction of anteroposterior soft tissue changes was quite inaccurate. Changes in the vertical dimension were also more marked in the genioplasty group. The lower lip also showed a variable response, particularly in the genioplasty group, where the mean ratio was 0.5 mm lip advancement per 1.0 mm skeletal change, but again a range of 4.0 mm in either direction. There were no meaningful changes 1 year after surgery. PMID- 1598896 TI - A comparison of outcomes of orthodontic and surgical-orthodontic treatment of Class II malocclusion in adults. AB - The treatment outcome for skeletal Class II malocclusion was reviewed in 33 nongrowing patients who were treated with orthodontics alone (by premolar extraction and tooth movement to camouflage the skeletal problem) and in 57 patients treated for similar problems with surgery and orthodontics (with mandibular advancement and with tooth movement to reduce rather than increase dental compensation for the skeletal deformity). Cephalometric and dental cast changes were scored to quantitate treatment effects. Two approaches were used to determine the treatment efficacy (the relative success of treatment): (1) whether the final value for a measurement criterion (such as an overjet and an ANB angle) fell within the normal range, and (2) the quantitative amount of correction produced relative to an "ideal" value. In addition, a panel of judges was used to rate esthetic changes from pretreatment and posttreatment facial slides. Both orthodontic treatment and surgical-orthodontic treatment improved the malocclusion as judged from dental casts. Surgery resulted in greater reduction of overjet and greater improvement in most cephalometric skeletal, dental, and soft tissue criteria. Before treatment, the surgical patients had lower esthetic ratings than the orthodontics-only patients. After treatment, the esthetic ratings for the orthodontic patients were unchanged. The surgical patients had improved but not to the pretreatment level of the orthodontics patients. PMID- 1598897 TI - A simple technique to minimize patient cross-contamination. PMID- 1598898 TI - Terminating the doctor-patient relationship: abandonment or not? PMID- 1598899 TI - Evidence for genetic heterogeneity of malignant hyperthermia susceptibility. AB - A locus for malignant hyperthermia susceptibility (MHS) has been localized on chromosome 19q12-13.2, while at the same time the gene encoding the skeletal muscle ryanodine receptor (RYR1) also has been mapped to this region and has been found to be tightly linked to MHS. RYR1 was consequently postulated as the candidate for the molecular defect causing MHS, and a point mutation in the gene has now been identified and is thought to be the cause of MH in at least some MHS patients. Here we report the results of a linkage study done with 19q12-13.2 markers, including the RYR1 cDNA, in two Bavarian families with MHS. In one of the families, three unambiguous recombination events between MHS and the RYR1 locus were found. In the second family only one informative meiosis was seen with RYR1. However, segregation analysis with markers for D19S75, D19S28, D19S47, CYP2A, BCL3, and APOC2 shows that the crossovers in the first family involve the entire haplotype defined by these markers flanking RYR1 and, furthermore, reveals multiple crossovers between these haplotypes and MHS in the second family. In these families, pairwise and multipoint lod scores below -2 exclude MHS from an interval spanning more than 26 cM and comprising the RYR1 and the previously described MHS locus. Our findings thus strongly suggest genetic heterogeneity of the MHS trait and prompt the search for another MHS locus. PMID- 1598900 TI - Sex-chromosome pairing: evidence that the behavior of the pseudoautosomal region differs during male and female meiosis. AB - In humans, recombination in the pseudoautosomal region is approximately 10-fold higher in males than in females. This difference is thought to reflect the fact that, in females, there is opportunity for genetic exchange along the entire length of the X chromosome, resulting in a relative reduction in the likelihood of exchange in the pseudoautosomal region. In two instances in the laboratory mouse where X-chromosome pairing and exchange in females are limited to the pseudoautosomal region, a significant level of X-chromosome pairing failure was observed at diakinesis/metaphase I. Further analysis indicated that, in female meiosis, the inability of the X chromosome to consistently form a pairing configuration via the pseudoautosomal region alone is not a property of the pseudoautosomal region per se but is due to the fact that it resides on an X chromosome. Thus previously reported sex-linked differences in recombination rate in the pseudoautosomal region may actually reflect differences in pairing and/or recombination of the pseudoautosomal region on an X chromosome undergoing male versus female meiosis. PMID- 1598901 TI - Detection and characterization of point mutations in the choroideremia candidate gene by PCR-SSCP analysis and direct DNA sequencing. AB - By making use of positional cloning strategies we recently isolated a candidate gene for choroideremia (CHM), which is transcribed in retina, choroid, and/or retinal pigment epithelium. The gene contains an open reading frame that is structurally altered in 10 CHM patients with sizable deletions and in a female patient with a balanced translocation involving the Xq21 band. Employing PCR-SSCP analysis and direct DNA sequencing we have now detected and characterized different point mutations in five patients with CHM. Each of these mutations introduces a termination codon into the open reading frame of the CHM candidate gene, thereby predicting a distinct truncated protein product. Together these findings provide convincing evidence for the candidate gene being identical with the choroideremia gene. PMID- 1598902 TI - Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q. AB - Limb-girdle muscular dystrophy (LGMD) is a clinically and genetically heterogenous group of disorders, with both recessive and dominant forms reported. Recently, a series of recessive LGMD families were linked to chromosome 15q. We report herein the results of our linkage studies in a previously reported large autosomal dominant family. The LGMD gene in this family was localized to chromosome 5q22.3-31.3 by using a series of CA(n) microsatellite repeat markers. Linkage to 15q was excluded. These findings confirm genetic heterogeneity in this clinically diverse syndrome. PMID- 1598903 TI - Linkage of familial breast cancer to chromosome 17q21 may not be restricted to early-onset disease. AB - Lod scores for linkage between familial breast and ovarian cancer and markers on chromosome 17q21 are more frequently positive among families with disease diagnosed at younger ages than they are among older-onset families, suggesting that linkage is restricted to early-onset disease. However, for late-onset cases, the relative probability of sporadic rather than inherited disease is higher than previously suggested. If this correction is made, then later-onset families are much less informative; linkage heterogeneity based on age at onset is no longer significant; and for the sample of families as a whole, linkage is significant at a recombination fraction since demonstrated to be close to the correct local. There is probably more than one gene for inherited breast cancer, but heterogeneity may not be due to age at disease onset. PMID- 1598904 TI - Closing in on a breast cancer gene on chromosome 17q. AB - Linkage of early-onset familial breast and ovarian cancer to 11 markers on chromosome 17q12-q21 defines an 8-cM region which is very likely to include the disease gene BRCA 1. The most closely linked marker is D17S579, a highly informative CA repeat polymorphism. D17S579 has no recombinants with inherited breast or ovarian cancer in 79 informative meioses in the seven families with early-onset disease (lod score 9.12 at zero recombination). There is no evidence for linkage heterogeneity in the families with early-onset disease. The proportion of older-onset breast cancer attributable to BRCA 1 is not yet determinable, because both inherited and sporadic cases occur in older-onset families. PMID- 1598905 TI - A new test for linkage in the presence of locus heterogeneity. AB - The detection of linkage in complex traits, although potentially of the greatest value, has proved very difficult. One reason may be the drastic effect that locus heterogeneity has on statistical power. We propose a new test for linkage in the presence of heterogeneity, based upon the sum of individual pedigree maximum lod scores, combined with a bootstrap method for estimating the null-hypothesis distribution. The technique is designed to exploit modern computer capability and to avoid reliance on asymptotic-distribution theory. Numerical comparisons indicate that for small pedigrees this new test can detect linkage with 30%-50% less data than are required by standard methods. A computer program for simulating the distribution and for performing the test of linkage is available from the authors. PMID- 1598906 TI - Software for analysis and manipulation of genetic linkage data. AB - We present eight computer programs written in the C programming language that are designed to analyze genotypic data and to support existing software used to construct genetic linkage maps. Although each program has a unique purpose, they all share the common goals of affording a greater understanding of genetic linkage data and of automating tasks to make computers more effective tools for map building. The PIC/HET and FAMINFO programs automate calculation of relevant quantities such as heterozygosity, PIC, allele frequencies, and informativeness of markers and pedigrees. PREINPUT simplifies data submissions to the Centre d'Etude du Polymorphisme Humain (CEPH) data base by creating a file with genotype assignments that CEPH's INPUT program would otherwise require to be input manually. INHERIT is a program written specifically for mapping the X chromosome: by assigning a dummy allele to males, in the nonpseudoautosomal region, it eliminates falsely perceived noninheritances in the data set. The remaining four programs complement the previously published genetic linkage mapping software CRI MAP and LINKAGE. TWOTABLE produces a more readable format for the output of CRI MAP two-point calculations; UNMERGE is the converse to CRI-MAP's merge option; and GENLINK and LINKGEN automatically convert between the genotypic data file formats required by these packages. All eight applications read input from the same types of data files that are used by CRI-MAP and LINKAGE. Their use has simplified the management of data, has increased knowledge of the content of information in pedigrees, and has reduced the amount of time needed to construct genetic linkage maps of chromosomes. PMID- 1598907 TI - A missense mutation (Trp86----Arg) in exon 3 of the lipoprotein lipase gene: a cause of familial chylomicronemia. AB - We have investigated a patient of English ancestry with familial chylomicronemia caused by lipoprotein lipase (LPL) deficiency. DNA sequence analysis of all exons and intron-exon boundaries of the LPL gene identified two single-base mutations, a T----C transition for codon 86 (TGG) at nucleotide 511, resulting in a Trp86--- Arg substitution, and a C----T transition at nucleotide 571, involving the codon CAG encoding Gln106 and producing Gln106----Stop, a mutation described by Emi et al. The functional significance of the two mutations was confirmed by in vitro expression and enzyme activity assays of the mutant LPL. Linkage analysis established that the patient is a compound heterozygote for the two mutations. The Trp86----Arg mutation in exon 3 is the first natural mutation identified outside exons 4-6, which encompass the catalytic triad residues. PMID- 1598909 TI - Mutation in the alpha 5(IV) collagen chain in juvenile-onset Alport syndrome without hearing loss or ocular lesions: detection by denaturing gradient gel electrophoresis of a PCR product. AB - A single base mutation was identified in the type IV collagen alpha 5 chain gene (COL4A5) of a Danish kindred with Alport syndrome. The 27-year-old male proband developed hematuria in childhood and terminal renal failure at the age of 25 years. He has no hearing loss or ocular lesions. Electron microscopy demonstrated splitting of the lamina densa of the glomerular basement membrane. The proband's mother has had persistent microscopic hematuria since the age of 40 years, but no other manifestations. Southern analysis of MspI-digested genomic DNA from the proband showed the absence of 1.3-kb and 0.9-kb fragments present in control DNA but the presence of a 2.2-kb variant fragment, indicating the loss of an MspI restriction site in the 3' end of the gene. The mother had all three fragments, indicating heterozygosity. PCR amplification of exon 14 (counted from the 3' end) and subsequent denaturing gradient gel electrophoresis analysis suggested a sequence variant in the proband and his mother. This was confirmed by sequencing of the PCR-amplified exon 14 region of the hemizygous proband, which demonstrated the base change G----A abolishing an MspI restriction site. Hybridization analysis with allele-specific probes confirmed the inheritance of the mutation with the phenotype. The mutation changed the GGC codon for glycine-1143 to GAC for aspartate. Substitution of glycine-1143, located in the collagenous domain of the alpha 5(IV) chain, for any other amino acid can be expected to interfere with the maintenance of the triple-helical conformation of the collagen molecule. This could, in turn, weaken the glomerular-basement-membrane framework and lead to increased permeability. PMID- 1598908 TI - Molecular genetic study of human arginase deficiency. AB - We have explored the molecular pathology in 28 individuals homozygous or heterozygous for liver arginase deficiency (hyperargininemia) by a combination of Southern analysis, western blotting, DNA sequencing, and PCR. This cohort represents the majority of arginase-deficient individuals worldwide. Only 2 of 15 homozygous patients on whom red blood cells were available had antigenically cross-reacting material as ascertained by western blot analysis using anti-liver arginase antibody. Southern blots of patient genomic DNAs, cut with a variety of restriction enzymes and probed with a near-full-length (1,450-bp) human liver arginase cDNA clone, detected no gross gene deletions. Loss of a TaqI cleavage site was identified in three individuals: in a homozygous state in a Saudi Arabian patient at one site, at a different site in homozygosity in a German patient, and in heterozygosity in a patient from Australia. The changes in the latter two were localized to exon 8, through amplification of this region by PCR and electrophoretic analysis of the amplified fragment after treatment with TaqI; the precise base changes (Arg291X and Thr290Ser) were confirmed by sequencing. It is interesting that the latter nucleotide variant (Thr290Ser) was found to lie adjacent to the TaqI site rather than within it, though whether such a conservative amino acid substitution represents a true pathologic mutation remains to be determined. We conclude that arginase deficiency, though rare, is a heterogeneous disorder at the genotypic level, generally encompassing a variety of point mutations rather than substantial structural gene deletions. PMID- 1598910 TI - The Y-associated XY275 low allele is not restricted to indigenous African peoples. AB - The level of linkage disequilibrium between the XY275 MspI polymorphism and the X and Y boundaries was investigated in 21 different southern African populations. A full range of frequencies of the high allele was observed on the 1,013 X chromosomes studied, in keeping with published data. In previous studies fixation of the high allele on the Y chromosome was observed in all but two groups--a Pygmy and a Tsumkwe San population. However, in the present study of 673 Y chromosomes, the low allele was found to be associated with the Y chromosome in several different Bantu-speaking negroid groups, the Khoisan-speaking negroid Dama, the Khoisan, two groups of mixed ancestry, and the South African Asiatic Indian population. The discovery of the low allele on Y chromosomes of caucasoid individuals suggests that more than one class of Y chromosome gave rise to the present-day non-African population. The data also fail to provide support for the theory that Africa is the site of origin of Homo sapiens, but they equally do not exclude it. PMID- 1598911 TI - Segregation analysis detects a major gene controlling blood infection levels in human malaria. AB - The profound influence that the genetic makeup of the host has on resistance to malaria infection has been established in numerous animal studies. This genetic heterogeneity is one of the main causes of the difficulties in developing an effective malaria vaccine. Segregation analysis is the first step in identifying the nature of genetic factors involved in the expression of human complex diseases, as infectious diseases. To assess the role of host genes in human malaria, we performed segregation analysis of blood parasite densities in 42 Cameroonian families by using both the unified mixed model and the class D regressive model of analysis. The results provide clear evidence for the presence of a recessive major gene controlling the degree of infection in human malaria. Parameter estimates show a frequency of .44-.48 for the deleterious allele, indicating that about 21% of the population is predisposed to high levels of infection. PMID- 1598912 TI - Point mutation in the DNA binding domain of the androgen receptor in two families with Reifenstein syndrome. AB - Inadequate androgen action in genetic and gonadal males causes an intersex phenotype. We have analyzed the androgen receptor (AR) gene in male pseudohermaphrodites with normal specific binding of dihydrotestosterone in their genital skin fibroblasts. In five patients with Reifenstein syndrome we have detected a point mutation in the DNA binding domain. They are from two unrelated families and presented with perineoscrotal hypospadias and undescended testes. After puberty they showed small testes, no palpable prostate, micropenis, azoospermia, and gynecomastia. The mutation was discovered when cDNA fragments from three brothers were sequenced. For rapid detection of the mutation in heterozygous and hemizygous carriers, allele-specific PCRs and restriction analysis techniques have been developed. Relatives of the patients, a group of normal blood donors, and other patients were screened with these methods. Among 41 intersex patients with incomplete virilization, another two brothers presenting with this mutation were identified. The mutation is a guanine-to adenine transition at nucleotide 2314, which changes the alanine codon (GCC) immediately after the first cysteine of the second zinc finger motif of the AR into a threonine codon (ACC). The mutation was recreated in an AR expression vector, and wild-type as well as mutant ARs were expressed in COS-7 cells. Cotransfection experiments were made using a mouse mammary tumor virus chloramphenicol acetyltransferase reporter gene. The ability of the mutant receptor to stimulate transcription of the reporter gene was reduced by about two thirds, as compared with the wild-type receptor. PMID- 1598913 TI - Rh segregation distortion: an artifact of ascertainment bias? AB - On the basis of Rh blood group data on mother-child pairs collected from the maternity clinic of a hospital in Chile, Valenzuela and Harb postulated that there is a significant segregation distortion at the Rh locus. For data collected from a hospital, biases of ascertainment cannot be ruled out. For the Rh blood group locus, there is a strong possibility of preferential admission of Rh(-) pregnant women, especially of those Rh(-) women with Rh(+) husbands. We show that the evidence of segregation distortion vanishes when the possibility of such preferential admissions are taken into account. PMID- 1598914 TI - The sequence of human mtDNA: the question of errors versus polymorphisms. PMID- 1598915 TI - Ataxia-telangiectasia: linkage evidence for genetic heterogeneity. PMID- 1598916 TI - Uniparental disomy 15 resulting from "correction" of an initial trisomy 15. PMID- 1598917 TI - On the economics of clinical genetic services in academic institutions. PMID- 1598919 TI - Determining clinical competencies of a prospective employee. PMID- 1598918 TI - Reporting of adverse drug reactions and physician liability. PMID- 1598920 TI - DUE uncovers lost opportunity for savings in laboratory costs. PMID- 1598921 TI - Potential compliance problems with vancomycin oral solution. PMID- 1598922 TI - Preparation of sterile talc for treatment of pleural effusion. PMID- 1598923 TI - Medication billing accuracy by anesthesia staff. PMID- 1598924 TI - Opportunities for pharmacists in support groups. PMID- 1598925 TI - Applause for ASHP-APhA-NARD joint statement on the entry-level degree. PMID- 1598926 TI - Reasons for the trend toward Pharm.D. education. PMID- 1598927 TI - Alternative interpretation for data. PMID- 1598928 TI - Pharmacy departments should be managed by pharmacists. PMID- 1598929 TI - Protecting patients from medication errors. PMID- 1598930 TI - Decision analysis to assess cost-effectiveness of low-osmolality contrast medium for intravenous urography. AB - Decision analysis was used to compare the cost-effectiveness of a conventional ionic high-osmolality contrast medium with that of a nonionic low-osmolality contrast medium when used for i.v. urography. The patient populations considered in the model were those with a low risk and those with a high risk of contrast medium-associated adverse effects. Mean toxicity rates for the contrast media were obtained from the literature. To estimate the average cost of adverse effects, the probability of a patient in each population developing a mild, moderate, or severe reaction was multiplied by the respective estimated cost for each level of severity, and the products were summed. The incremental cost of the low-osmolality medium per case of adverse effects prevented was calculated by dividing the difference between the average costs of the two media by the difference between the frequencies of toxicity associated with the agents. According to the 1990 cost data used, combined mean drug and toxicity costs were $68 and $13 for the low- and high-osmolality contrast media, respectively, per high-risk patient and $67 and $10 per low-risk patient. The incremental costs of the low-osmolality medium per case of severe adverse effects prevented was $17,974 in the high-risk population and $77,027 in the low-risk population. Sensitivity analysis showed the results to be stable over a range of data used in the model.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598931 TI - Audits of radiopharmaceutical formulations. AB - A procedure for auditing radiopharmaceutical formulations is described. To meet FDA guidelines regarding the quality of radiopharmaceuticals, institutional radioactive drug research committees perform audits when such drugs are formulated away from an institutional pharmacy. All principal investigators who formulate drugs outside institutional pharmacies must pass these audits before they can obtain a radiopharmaceutical investigation permit. The audit team meets with the individual who performs the formulation at the site of drug preparation to verify that drug formulations meet identity, strength, quality, and purity standards; are uniform and reproducible; and are sterile and pyrogen free. This team must contain an expert knowledgeable in the preparation of radioactive drugs; a radiopharmacist is the most qualified person for this role. Problems that have been identified by audits include lack of sterility and apyrogenicity testing, formulations that are open to the laboratory environment, failure to use pharmaceutical-grade chemicals, inadequate quality control methods or records, inadequate training of the person preparing the drug, and improper unit dose preparation. Investigational radiopharmaceutical formulations, including nonradiolabeled drugs, must be audited before they are administered to humans. A properly trained pharmacist should be a member of the audit team. PMID- 1598932 TI - Pharmacoeconomic evaluation of treatment of penetrating abdominal trauma. AB - The hospital, pharmacy, and antibiotic costs for patients with penetrating abdominal trauma were compared with reimbursement received; these costs were also analyzed to assess the potential impact of a total prospective pricing system (PPS). During a four-year period, 46 patients admitted solely for penetrating abdominal trauma were retrospectively evaluated: their discharge summaries indicated that, for 9 patients, reimbursement was based on diagnosis-related groups (DRGs) under the PPS; 9 patients had private insurance; and 28 were classified as "self-paying/no insurance." All costs, corrected for inflation, were reported in 1989 dollars. Antibiotics represented 22.5%, 1.7%, and 0.5% of pharmacy, hospital, and DRG reimbursement, respectively; pharmacy costs were 8.5% of hospital costs and 2.3% of DRG reimbursement. For all 46 patients, a net loss of $295 per patient was incurred. Four patients accounted for 43% of the hospital costs. If the hospital had been reimbursed for all of these patients by prospective pricing and DRGs, it would have had a median profit of $9730 in 42 of 46 patients. Costs exceeded DRG reimbursement in the remaining four patients by a median of $8210. Antibiotic costs and pharmacy costs represent a small portion of hospital costs and DRG reimbursement for patients with penetrating abdominal trauma; thus, cost containment efforts in these patients should be directed at other ancillary services and length of stay. PMID- 1598933 TI - Drug information service for drug product procurement in the Veterans Affairs health-care system: preliminary experience. AB - The preliminary experience of the drug information service of the Department of Veterans Affairs (VA) central office is described. The drug information service assists the drug and pharmaceutical product management section of the pharmacy service for the VA central office. The purpose of the drug information service is to promote efficacious drug therapy while meeting cost containment goals for pharmaceutical products. The pharmacist coordinator of this service has experience in both patient care and drug information service. The drug information service is involved in the following activities: (1) making recommendations for contract bidding on therapeutically equivalent products, (2) identifying prescription duplication within the system, (3) reporting product defects, (4) planning drug procurement in unique situations, such as during war, (5) developing gender-specific therapy, (6) evaluating the appropriateness of brand-name-only purchasing of certain products, (7) evaluating new drug products, (8) compiling national drug-use data, and (9) projecting drug price increases. The VA drug information service has diverse responsibilities meant to optimize drug therapy and reduce pharmacy costs in the VA health-care system. PMID- 1598934 TI - Factors affecting practice-area choices by pharmacy students in the Midwest. AB - The results of a survey to determine the first-choice practice intentions of midwestern pharmacy students and to describe and quantify the factors affecting their decisions are reported. Questionnaires were sent to 12 pharmacy schools in American Association of Colleges of Pharmacy District IV and distributed during November 1988 to January 1989. The questionnaires were given to entry-level pharmacy students who were in their final year of study. The students were asked to indicate their preferred practice setting upon graduation and to rate the importance of 21 factors that a pharmacist might consider when selecting a first position. A total of 715 usable responses were received (response rate, 6.75%). OF the respondents, 83.2% were enrolled in B.S. degree programs and 16.8% in entry-level Pharm.D. degree programs. The distribution of first choices of a practice area was as follows: chain community pharmacy, 33.1%; hospital pharmacy, 27.6%; independent community pharmacy, 12.4%; industry, 8.4%; "other," 5.5%; ambulatory-care clinic, 5.2%; graduate school, 3.8%; department store, discount store, or grocery store, 1.7%; home health care, 1.5%; and nursing home, 0.8%. The three factors ranked as most important in affecting the choice of a practice area were personal fulfillment, salary, and the opportunity to use one's abilities and education. The ranking of the factors varied depending on the practice area chosen. Midwestern pharmacy students were most interested in chain community and hospital pharmacy practice settings. Retail-oriented students placed salary concerns first, whereas clinically oriented students emphasized personal fulfillment. These findings have implications for recruitment strategies. PMID- 1598935 TI - Causes of non-medication-induced nasogastric tube occlusion. AB - In vitro simulation of nasogastric tube delivery of enteral formulas was used to study the mechanism and prevention of non-medication-induced nasogastric tube occlusion. Enteral nutrition products--Osmolite, Ensure, Vital High Nitrogen, and Vivonex T.E.N.--were placed in glass beakers and titrated with hydrochloric acid to determine the pH at which clotting would occur. Factors such as pH, protein content, viscosity, electrolyte composition, flow rate, and tube design were evaluated to determine their effects on coagulation of formula. Addition of simethicone emulsion and docusate sodium to the formulas and siliconization of the nasogastric tubes were studies for their effect on prevention of clog formation. Clumping began to occur at pH 4.6 (the isoelectric point for casein) for Ensure and Osmolite; addition of protein supplement did not change the pH at which coagulation occurred. Vital High Nitrogen and Vivonex T.E.N. formulations did not clump in the beakers. Ensure and Osmolite coagulated within 35 seconds at pH 4.6 or less and remained unchanged at pH greater than 6.0. Addition of sodium or calcium caseinate greatly increased the tendency of the formulas to coagulate. Viscosity of the formula increased markedly as pH decreased. Addition of electrolytes had no effect on precipitation or clumping. Slow or no flow rates within nasogastric tubes placed in simulated gastric juice decreased the pH and caused clumping of formulas within the tubes in a retrograde manner. Flow time or clog formation was not affected by the addition of simethicone or docusate sodium or siliconization of the nasogastric tube.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598936 TI - Biological activity of recombinant interleukin-2 in intravenous admixtures containing antibiotic, morphine sulfate, or total parenteral nutrient solution. AB - The biological activity of recombinant interleukin-2 in intravenous admixtures containing gentamicin sulfate, tobramycin sulfate, amikacin sulfate, ticarcillin disodium, piperacillin sodium, morphine sulfate, or total parenteral nutrient (TPN) solution was investigated. Recombinant interleukin-2 in a formulation containing human serum albumin was diluted to a therapeutic dose and mixed with the other drugs in test tubes to simulate mixing distal to the Y-site of an i.v. administration set. All test tubes were visually observed for precipitates. Triplicate test samples of recombinant interleukin-2 and interleukin-2 with drug were added to microplate wells containing lymphocyte tissue culture media (an interleukin-2-dependent murine cytotoxic T cell line, CTLL-2) using serial dilutions. The microplates were incubated then pulsed with mouse lymphocyte media containing tritiated thymidine (3H-thymidine). The amount of 3H-thymidine incorporated into lymphocyte DNA was measured using a beta counter. The average counts per minute (cpm) of a sample was analyzed as a function of the logarithm of sample dilution; one interleukin-2 unit was defined as 50% of the maximum cpm measured in the samples. At minimum dilutions, ticarcillin disodium reduced the effect of interleukin-2 on CTLL-2 growth; the other antibiotics and morphine sulfate had no effect. Interleukin-2 mixed with TPN solutions showed slightly enhanced growth of the CTLL-2 line compared with the interleukin-2 standard. Mixtures of multiple antibiotics, morphine, and TPN solutions with and without 20% fat emulsion had no effect on interleukin-2 activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598937 TI - Stability of captopril in tap water. AB - The stability of captopril in tap water was studied. Twenty 25-mg captopril tablets were crushed separately, added to 25 mL of tap water in individual volumetric flasks, and shaken vigorously. Five flasks each were incubated at 25, 50, and 75 degrees C in a shaking water bath and refrigerated at 5 degrees C. Samples were taken from each flask immediately after dissolving the drug and at intervals up to 28 days for 5 and 25 degrees C, 15 days for 50 degrees C, and 16 days for 75 degrees C. Captopril concentrations were analyzed by high-performance liquid chromatography. First-order rate constants were calculated for each temperature setting, and the Arrhenius plot was applied to estimate the shelf life of captopril at 5 degrees C. More than 90% of the initial concentration of captopril remained after 28 days at 5 degrees C. Captopril concentration in the samples stored at 75, 50, and 25 degrees C decreased to 90% of the initial concentration at calculated times (mean +/- S.E.) of 2.1 +/- 0.1, 3.6 +/- 0.4, and 11.8 +/- 1.2 days, respectively. The estimated time required for the concentration of a 1-mg/mL solution of captopril stored at 5 degrees C to decrease to 90% of initial concentration was 27 days. The shelf life of a solution of captopril 1 mg/mL in tap water stored at 5 degrees C was 27 days. PMID- 1598938 TI - Stability of midazolam hydrochloride in a flavored, dye-free oral solution. AB - The stability of injectable midazolam hydrochloride in a solution for oral use was studied at three temperatures over 56 days. A 2.5-mg/mL oral solution was prepared from injectable midazolam hydrochloride and a flavored, dye-free syrup. Samples of solution were stored in amber glass bottles at 7, 20, or 40 degrees C. Duplicate samples were analyzed by high-performance liquid chromatography on days 0, 1, 3, 5, 14, 21, 35, and 56. Samples were also visually inspected on each sampling day. The concentrations of all samples remained greater than 90% of the original concentration and there were no visual signs of microbial growth or changes in color, turbidity, or odor throughout the 56-day period. A 2.5-mg/mL solution of injectable midazolam in syrup was stable for 56 days at 7, 20, or 40 degrees C. PMID- 1598939 TI - Stability of fluorouracil, cytarabine, or doxorubicin hydrochloride in ethylene vinylacetate portable infusion-pump reservoirs. AB - The stability of fluorouracil, cytarabine, and doxorubicin hydrochloride in admixtures stored in portable infusion-pump reservoirs was investigated. Admixtures containing fluorouracil 50 or 10 mg/mL, cytarabine 25 or 1.25 mg/mL, or doxorubicin hydrochloride 1.25 or 0.5 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection were placed in 80-mL ethylene vinylacetate drug reservoirs protected from light, and 1-mL quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 7, 14, and 28 days at 4, 22, or 35 degrees C. For each condition, three samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change, and pH. Evaporative water loss from the containers was measured. Fluorouracil was stable at all temperatures for 28 days. Cytarabine was stable for 28 days at 4 and 22 degrees C and for 7 days at 35 degrees C. Doxorubicin hydrochloride was stable for 14 days at 4 and 22 degrees C and for 7 days at 35 degrees C. No color change or precipitation was observed, and pH values were stable. Loss of water through the reservoirs was substantial only at 35 degrees C for 28 days. When stored in ethylene vinylacetate portable infusion-pump reservoirs, fluorouracil, cytarabine, and doxorubicin hydrochloride were each stable for at least one week at temperatures up to 35 degrees C. Cytarabine and doxorubicin hydrochloride showed decreasing stability at longer storage times and higher temperatures. PMID- 1598940 TI - Pharmacy-based medication administration by licensed practical nurses. PMID- 1598941 TI - Generic versus brand name drug prescribing by resident physicians in Pennsylvania. PMID- 1598942 TI - Drug interaction monitoring program in a community hospital. PMID- 1598943 TI - Use of criteria developed before formulary addition to evaluate misoprostol use. PMID- 1598944 TI - Effect of a criteria-based cost-containment program on the selection of oral H2 receptor antagonists. PMID- 1598945 TI - Patients' perceived understanding of informed consent in investigational drug studies. PMID- 1598946 TI - Prison pharmacist may be liable for refusing to dispense anticonvulsants to an inmate. PMID- 1598947 TI - Draft guidelines on preventable medication errors. PMID- 1598948 TI - ASHP guidelines on formulary system management. PMID- 1598949 TI - Summary of the ASHP therapeutic guidelines for intravenous immune globulin. ASHP Commission on Therapeutics. PMID- 1598950 TI - Inpatient antimicrobial use in two hospitals near Tel Aviv. PMID- 1598951 TI - Transsclerally sutured intraocular lenses in penetrating keratoplasty. AB - We reviewed the charts of 114 consecutive patients who underwent penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens. Two patients died within three months of follow-up and were excluded from the study. In the remaining 112 patients, follow-up ranged from four to 47 months (mean, 17.2 months). Postoperative visual acuity improved in 95 patients (85%), remained the same in 13 patients (11.5%), and worsened in four patients (3.5%). In 71 patients with at least one year of follow-up, best-corrected visual acuity was 20/40 or better in 17 patients (24%), 20/50 to 20/80 in 25 patients (35%), 20/100 to 20/400 in 17 patients (24%), and counting fingers or worse in 12 patients (17%). Problems with lens decentration, tilt, dislocation, or scleral suture-related infections were minimal. Glaucoma and cystoid macular edema were the most common causes of decreased visual acuity. Four patients (3.6%) developed intraoperative choroidal detachments. Three patients (2.7%) developed rhegmatogenous retinal detachments early in the postoperative course. PMID- 1598952 TI - Simultaneous corneal laceration repair, cataract removal, and posterior chamber intraocular lens implantation. AB - Frequently, patients with lens laceration or traumatic cataract coincident with corneal laceration, or both, must undergo two separate procedures-primary repair of the corneal laceration and secondary lens removal with or without intraocular lens implantation. We performed simultaneous corneal laceration repair, extracapsular cataract extraction, and posterior chamber lens implantation in seven patients with lacerating ocular injuries who met inclusion criteria for this procedure. With average follow-up of 10 1/2 months, all seven patients achieved visual acuity of 20/40 or better with spectacle correction. YAG posterior capsulotomy was the only additional procedure. One patient had macular pigmentation consistent with either traumatic or photic maculopathy. There were no other complications attributable to the surgical procedures. We believe that certain lacerating injuries of the anterior segment are particularly amenable to cataract extraction and lens implantation at the time of primary laceration repair. This approach obviates additional operative and anesthetic risks, while affording more timely visual rehabilitation. PMID- 1598953 TI - Efficacy and safety of lodoxamide 0.1% vs cromolyn sodium 4% in patients with vernal keratoconjunctivitis. AB - A multicenter, double-masked, parallel-group clinical study compared the efficacy and safety of lodoxamide 0.1% ophthalmic solution and cromolyn sodium 4% ophthalmic solution in 120 patients with vernal keratoconjunctivitis. On various follow-up visits, the clinical efficacy of lodoxamide 0.1% was statistically superior to cromolyn sodium 4% in alleviating four of the primary symptoms (itching, tearing, foreign-body sensation, and discomfort) and five of the primary signs (Trantas' dots, palpebral conjunctival changes, bulbar conjunctival hyperemia, erythema/swelling of the eyelids and periorbital tissues, and epithelial disease). At no time during the study was cromolyn sodium 4% statistically superior to lodoxamide 0.1% in demonstrating improvements in clinical signs and symptoms of vernal keratoconjunctivitis. The physician's clinical judgment of patients' response to treatment showed lodoxamide 0.1% effected a greater and earlier improvement than cromolyn sodium 4%. Both drugs were safe for topical ophthalmic use when used four times daily for up to 28 days. PMID- 1598954 TI - Topically administered norfloxacin compared with topically administered gentamicin for the treatment of external ocular bacterial infections. The Worldwide Norfloxacin Ophthalmic Study Group. AB - In this double-masked study, we randomly assigned 488 patients with clinical signs of acute bacterial conjunctivitis or blepharitis, or both, to treatment with either norfloxacin ophthalmic solution 0.3% (245) or gentamicin ophthalmic solution 0.3% (243) for one week. Of the patients with positive cultures, 71% (85 of 120) of the norfloxacin-treated patients and 65% (86 of 133) of the gentamicin treated patients were clinically cured. An additional 25% (30 of 120) of norfloxacin-treated patients and 32% (43 of 133) of gentamicin-treated patients were clinically improved. On the basis of posttreatment cultures, 89% of all cultured bacteria were eradicated (146 of 179 organisms) or suppressed (14 of 179 organisms) after treatment with norfloxacin. The condition of five norfloxacin treated patients did not clinically improve, compared with the condition of eight gentamicin-treated patients. Both antibiotics had similar efficacy against gram positive and against gram-negative organisms. One norfloxacin-treated patient and two gentamicin-treated patients withdrew from the study because of local intolerance. Norfloxacin appears to be an effective and relatively safe agent for the treatment of bacterial infections of the eyelids or conjunctiva, or both. In this study, norfloxacin was clinically and microbiologically similar in activity to gentamicin. PMID- 1598955 TI - Reliability coefficients of three corneal pachymeters. AB - We compared the accuracy and reproducibility of a hand-held portable ultrasound pachymeter, the Pach-Pen (Bio-Rad, Ophthalmic Division, Santa Ana, California); another ultrasound pachymeter, the DGH 1000 (DGH Technology, Inc., Frazer, Pennsylvania); and the Pro-Cem 4 endothelial specular microscope (Alcon-Surgical, Inc., Irvine, California). Each eye of 18 healthy human subjects was examined to determine corneal thickness using the three different instruments. For each instrument, five repeated measurements were obtained at each of five corneal locations (one central, four peripheral), for a total of 25 measurements per eye. The accuracy of the two ultrasound pachymeters was tested by comparing measurements obtained on specially designed test blocks of known thickness. The Pach-Pen was the more accurate of the two ultrasound pachymeters, with measurements within the range of 0.003 to 0.065 mm from the true thickness. The three instruments were most consistent in mean thickness in the center of the cornea. All three instruments showed excellent intraobserver reproducibility, as measured by reliability coefficients over 90%. Overall, the Pach-Pen pachymeter had high reproducibility, and produced more accurate measurements than the DGH 1000 pachymeter. PMID- 1598956 TI - Evolution of age-related macular degeneration with choroidal perfusion abnormality. AB - Prolonged choroidal filling on fluorescein angiography in age-related macular degeneration is thought to indicate diffuse thickening of Bruch's membrane. To test the importance of this clinical sign, we reviewed the evolution of disease in eyes of patients with good visual acuity and a readable transit phase of fluorescein angiography at the time of recruitment into a longitudinal study of age-related macular degeneration. Ninety-six eyes satisfied these criteria. Of the 32 eyes with prolonged choroidal filling, 12 (38%) lost two or more lines, of visual acuity by two years, whereas only nine of 64 (14%) eyes with normal choroidal filling did so. The difference was caused by the higher incidence of geographic atrophy in the first group. The proportion of eyes that developed subretinal neovascularization was the same in the two groups, and no pigment epithelial detachments occurred. These findings indicate that this clinical sign has implications concerning visual prognosis in age-related macular degeneration. PMID- 1598957 TI - Branch retinal vein occlusion and quadratic variation in arteriovenous crossings. AB - To explore further the origin and clinically observed regional variation of branch retinal vein occlusion, we studied fluorescein angiograms of 42 patients (42 eyes) with branch retinal vein occlusion and a control population of 126 consecutive patients. In a statistically significant percentage of crossings, the artery was anterior to the vein in those areas of the retina clinically predisposed to branch retinal vein occlusion. Thirty-nine of the 42 patients with branch retinal vein occlusion sites had artery-anterior-to-vein crossings (P = .002), whereas 183 of all 266 arteriovenous crossings in these same eyes were similarly positioned. The artery lay anterior to the vein in significantly more temporal retinal crossings (337 of 457) than nasal retinal crossings (89 of 149; P = .002). Similarly, significantly more superotemporal quadrant crossings (164 of 209) than inferotemporal quadrant crossings (173 of 248) had the artery anterior to the vein (P = .0045). These results suggested that variation in the pattern of arteriovenous crossings may have a role in the clinical distribution of branch retinal vein occlusion. PMID- 1598958 TI - Merkel cell carcinoma of the eyelid and periocular tissues. AB - Five patients had eyelid and periocular Merkel cell carcinoma. The tumor was located on the left lower eyelid in two patients, the left upper eyelid in one patient, the right upper eyelid in one patient, and was metastatic to the right outer canthus in one patient. The mean duration of symptoms was approximately four months. The diagnosis of Merkel cell carcinoma was not suspected clinically in any of the four primary eyelid cases, but was only established on histopathologic examination of biopsy specimens. Light microscopy disclosed carcinoma with small primitive cells in all five tumor biopsy specimens. Immunohistochemical studies showed neuron-specific enolase and keratin and transmission electron microscopy demonstrated neurosecretory granules typical for Merkel cell carcinoma. All five patients in this study were treated with wide surgical excision of the eyelid tumors with intraoperative frozen-section monitoring of the margins of resection. The left lower eyelid Merkel cell carcinoma spread to the preauricular lymph node in one patient. This patient subsequently died of metastatic Merkel cell carcinoma. One patient with metastatic right outer canthus Merkel cell carcinoma received radiotherapy (6,550 cGy). Eyelid Merkel cell carcinoma has the potential for recurrence and metastatic spread. We recommend lifetime follow-up for patients treated for eyelid Merkel cell carcinoma. PMID- 1598959 TI - Effects of eyelid protractor excision for the treatment of benign essential blepharospasm. AB - Data were analyzed from 37 patients with essential blepharospasm who had undergone upper eyelid protractor excision with brow suspension, and who had a median follow-up of 40 months (range, 12 to 83.5 months) after surgery. Of the 37 patients, 15 (40.5%) had sufficient relief of their spasms at their last follow up; 22 patients (59.5%) had functionally significant recurrent or residual spasms after upper eyelid surgery. Of these 22 patients, 12 (55%) had recurrences more than six months after surgery, and four patients (18%) had recurrences more than one year after surgery. Patients with Meige syndrome were no more likely to experience recurrent spasms after upper eyelid surgery than patients who lacked a lower facial spasm component. Recurrence of symptoms was primarily the result of lower eyelid spasms in 11 patients (50%), upper eyelid spasms in one patient (5%), and all eyelids in six patients (27%). The location of recurrent spasms could not be ascertained in four patients (18%), with whom we had only telephone contact. Seven of 12 patients (58%) undergoing secondary procedures had relief from their spasms at the end of this study. Excluding those patients who chose to decline further surgery, 22 of 27 patients (81.5%) received satisfactory relief of symptoms after upper eyelid and, if needed, lower eyelid and repeat upper eyelid protractor excision. These long-term results are comparable to those reported previously for differential section of the facial nerve. Because the side effects of eyelid protractor excision are generally more acceptable, we recommend that when surgery is determined to be necessary for essential blepharospasm, upper eyelid protractor excision is the preferred surgical approach. PMID- 1598960 TI - Combined use of cyclosporine and ketoconazole in the treatment of endogenous uveitis. AB - Ten patients with endogenous uveitis were in clinical remission attributable to treatment with cyclosporine and prednisone. After the cyclosporine dose was reduced by two thirds, these patients were randomly assigned to treatment with or without ketoconazole, a potent inhibitor of cytochrome P-450, in a double-masked placebo-controlled study. The dose was reduced over three days. During a three month follow-up, no patients treated with ketoconazole had a relapse of uveitis, while four of six (66%) control subjects had a flare-up. Toxicity in the ketoconazole-treated group was limited to a transient decrease in glomerular filtration rate (20% from baseline) at one month in two of six (33%) patients. Renal function was stabilized by further reduction of the cyclosporine dose. PMID- 1598961 TI - Ophthalmic manifestations of chronic angioedema with necrotizing vasculitis. AB - Anatomic features unique to periocular tissues alter the clinical appearance of angioedema, making it difficult to distinguish from cellulitis and other inflammatory conditions. Two patients had prominent periocular manifestations of chronic angioedema with necrotizing vasculitis, a systemic disease often associated with multiorgan involvement. The diagnosis was established by exclusion of other inflammatory disorders and confirmed by biopsy. The scarcity of reports in the ophthalmic literature on chronic angioedema of the eyelids may be caused by its underrecognition. The distinction between chronic angioedema and typical angioedema or urticaria is important because of differences in their diagnostic evaluation, treatment, and prognosis. PMID- 1598963 TI - Giant cell arteritis in the ocular ischemic syndrome. AB - Oculomotor nerve paresis, ocular hypotony, anterior segment ischemia, and the ocular ischemic syndrome are uncommon manifestations of giant cell arteritis. Four patients with these findings had giant cell arteritis documented by temporal artery biopsy. Cerebral angiography or ultrasonography, or both, performed in three patients, excluded hemodynamically significant stenosis of the internal carotid artery as the cause of ocular ischemia and cerebral aneurysms as the cause of oculomotor nerve paresis. Corticosteroid treatment, administered to three patients, resulted in resolution of the oculomotor deficits and the clinical signs of ocular ischemia, although the visual acuity in one patient improved from 20/400 to 20/60. Giant cell arteritis should be considered in the differential diagnosis of the ocular ischemic syndrome. PMID- 1598962 TI - Antibody affinity to retinal S-antigen in patients with retinal vasculitis. AB - Using a modified enzyme-linked immunosorbent antibody method that included dissociation of antigen antibody complexes with sodium thiocyanate, we examined the functional affinity of antibody to retinal S-antigen in 48 patients with retinal vasculitis and 46 age-matched healthy control subjects. Antibody affinity was markedly lower in patients with retinal vasculitis than in healthy subjects. Low-affinity antibody was more prevalent in acute retinal vasculitis and in patients with normal levels of circulating immune complexes. We found distinct differences between the antiretinal antibodies found in patients with retinal vasculitis and those in control subjects. The association of low-affinity antibody with normal levels of circulating immune complexes may suggest defective regulation of antiretinal autoimmunity and have important pathogenic implications. PMID- 1598964 TI - The effect of intracameral ethacrynic acid on the intraocular pressure of living monkeys. AB - Previous studies have shown that the sulfhydryl-reactive ethacrynic acid increases outflow facility in living monkeys when perfused via the anterior chamber. To study its potential clinical use further, living monkeys were intracamerally injected with 10 microliters of ethacrynic acid, with concentrations ranging from 0.5 to 7.5 mmol/l. The fellow control eye was injected with 10 microliters of diluent. The status of the anterior segment was monitored by slit-lamp biomicroscopy and the intraocular pressure was measured by pneumatonometry with the monkeys anesthetized with ketamine. The anterior segment of living monkeys tolerated injections up to 3.0-mmol/l ethacrynic acid without marked adverse effects. One of 13 monkey eyes injected with 3.0-mmol/l ethacrynic acid demonstrated mild reversible segmental corneal edema. The greatest mean intraocular pressure reduction in the 3.0- to 3.75-mmol/l group occurred at six hours, with the experimental intraocular pressure decreasing 2.9 mm Hg compared to a mean intraocular pressure increase of 0.1 mm Hg in the control group (n = 19). Concentrations of ethacrynic acid less than 3.0 mmol/l did not provide reliable reduction of intraocular pressure, whereas concentrations greater than 3.75 mmol/l caused a greater incidence and severity of corneal edema. We believe that the intracameral injection of ethacrynic acid can reliably and safely reduce intraocular pressure in living monkey eyes, and that this drug deserves further investigation as a potential antiglaucomatous agent. PMID- 1598965 TI - The gene for autosomal dominant familial exudative vitreoretinopathy (Criswick Schepens) on the long arm of chromosome 11. PMID- 1598966 TI - Proliferative vitreoretinopathy in fundus flavimaculatus. PMID- 1598967 TI - Joubert's syndrome, ocular fibrosis, and normal histidine levels. PMID- 1598968 TI - Stainless steel micropipette for subretinal surgery. PMID- 1598969 TI - Neovascular glaucoma secondary to sickle-cell retinopathy. PMID- 1598970 TI - Conjunctival cryptococcosis preceding human immunodeficiency virus seroconversion. PMID- 1598971 TI - Suppurative keratitis from herbal ocular preparation. PMID- 1598972 TI - Spontaneous resolution of a sunflower cataract. PMID- 1598974 TI - Bilateral conjunctival varix thromboses associated with habitual headstanding. PMID- 1598973 TI - Orbital aspergillosis in an immunocompromised host. PMID- 1598975 TI - Blepharochalasis associated with dermatomyositis and acute lymphocytic leukemia. PMID- 1598976 TI - Results and complications in treated retinal breaks. PMID- 1598977 TI - Acoustic tumors: effect of surgical removal on tinnitus. AB - Tinnitus is common in patients with acoustic tumors and may be the initial symptom leading to diagnosis. We might anticipate that tumor removal would alleviate preoperative tinnitus. However, few have studied this systematically. Further, the effect of tumor removal in those with no preoperative tinnitus has rarely been examined. In this study, a questionnaire was sent retrospectively to patients who had undergone surgical removal of an acoustic tumor, addressing the characteristics of tinnitus, and asking whether surgery had directly affected tinnitus. A total of 134 questionnaires were returned. Those who indicated preoperative tinnitus tended to show small but statistically significant improvements in the perceived severity of the tinnitus after surgery, although the symptom rarely resolved entirely. Those with no preoperative tinnitus have an approximately 50 percent chance of developing it following surgery. PMID- 1598978 TI - Chemical labyrinthectomy: local application of gentamicin for the treatment of unilateral Meniere's disease. AB - The use of aminoglycosides for selective vestibular function ablation without hearing alteration is described in the literature. Parenteral administration of streptomycin for the alleviation of vertigo in cases of bilateral Meniere's disease is well accepted. The instillation of aminoglycosides into the middle ear to produce a similar result, has been successfully used in the treatment of unilateral Meniere's disease. However, the use of chemical vestibulectomy has not gained acceptance as a practical means of treatment when compared to vestibular neurectomy. The reason for this is not clear, but may stem from the lack of definitive protocol for the application and lack of treatment results that have been assessed according to an acknowledged standard (i.e., the American Academy of Otolaryngology Criteria). A prospective study was undertaken to examine the efficacy of chemical vestibulectomy as the treatment for vertigo in unilateral, incapacitating Meniere's disease. A standardized drug administration protocol was utilized, and academy criteria for the assessment of treatment were applied. This report details the first group of patients to complete 2 years of post-treatment follow-up. Based on our experience, we conclude that chemical vestibulectomy is an efficient alternative to surgery. A standardized regimen of drug administration that can be carried out on an outpatient basis is put forward. PMID- 1598979 TI - Training the balance specialist. PMID- 1598980 TI - Vestibular neurectomy in the United States--1990. AB - During the last decade, vestibular neurectomy has become a more frequently performed procedure to cure symptoms of inner ear vertigo while preserving hearing. In an effort to determine the results of vestibular neurectomy across the country, a questionnaire was prepared and sent to the 350 members of the American Otologic Society and the American Neurotology Society. Results of that survey indicated that 2,820 vestibular neurectomy procedures were performed by 58 surgeons. Ninety-two percent (2,590 cases) were performed through the posterior fossa approach. Of these, 1149 cases (44%) were through the retrolabyrinthine approach, 940 cases (36%) were through the retrosigmoid approach, 307 cases (12%) were through the combined retrolabyrinthine-retrosigmoid approach, and 194 cases (8%) were unspecified as to which posterior fossa approach was used. The remaining 230 cases (8%) were through the middle fossa approach. Sectioning of the vestibular nerve was done by the otologist in 58 percent of cases, by the neurosurgeon in 12 percent, and by either surgeon in 30 percent. Classic Meniere's disease, the most common indication for vestibular neurectomy, resulted in the best cure rate of 91 percent. Other inner ear diseases such as traumatic labyrinthitis and vestibular neuronitis had a lower cure rate of 74 to 81 percent. Hearing was preserved to within 20 dB of the preoperative pure-tone thresholds in 87 percent. There were no deaths, 11 cases of meningitis and 16 cases of facial paralysis, 15 of which occurred after middle fossa surgery, representing a 7 percent incidence of facial paralysis after middle fossa surgery. Eleven of the 15 cases resulted in permanent paralysis and four in temporary paralysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598981 TI - The training of future otologists. PMID- 1598983 TI - Perilymphatic fistulae: more than a century of notions, conjectures, and critical studies. PMID- 1598982 TI - Inner ear morphology of experimental perilymphatic fistula. AB - The inner ear pathology of experimental perilymphatic fistula (EPLF) is described. EPLF was produced by injecting artificial perilymph into the subarachnoid space, or by suctioning 4 microL of perilymph through one of the round window membranes of the guinea pig. The animals were either killed immediately, or were kept alive for 3 weeks to 3 months. The conventional celloidin embedding method was employed for morphologic study. Vestibular function of the animals was tested by observing spontaneous nystagmus and positional nystagmus after the experiment. The caloric test was also performed. Various pathologic changes of the membranous labyrinth were observed. In the cochlea these included rupture or collapse of Reissner's membrane, bulging of Reissner's membrane, loss of hair cells, and compression of the organ of Corti. Pathology of the otolithic organs and semicircular canals mainly consisted of collapse of the membranous labyrinth. Clinical symptoms in patients with perilymphatic fistula (PLF) are explained, based on our experimental findings. Electronystagmography (ENG) of EPLF animals showed either no caloric response or, with a longer duration, caloric irregularity. Prolonged unsteadiness in patients may be due to "floating" labyrinth. PMID- 1598984 TI - Education of hearing-impaired children in the United States. PMID- 1598985 TI - Pressure transfer between the perilymph and the cerebrospinal fluid compartments in cats. AB - This is a review of our studies of the labyrinthine fluid pressure in cats subjected to pressure changes in the middle ear (implosive routes) and the cerebrospinal fluid compartment (explosive routes) as well as to changes in vascular and ambient pressures. The perilymph, cerebrospinal fluid (CSF), middle ear, venous and arterial pressures were measured with the cochlear aqueduct (CA) patent as well as surgically blocked. Experiments on explosive pressure changes revealed that the perilymph pressure was regulated by the CSF in case of CA patency. The CSF influence was dominant enough to obscure any direct effect on the labyrinth from other sources. With the CA obstructed the CSF influence on the labyrinth was apparently mainly via the endolymphatic sac and duct although limited and much delayed. Systemic arterial pressure changes had a pronounced influence on the perilymph pressure, but this effect was revealed only when the CSF influence was reduced by CA obstruction. Experiments on implosive and ambient pressure changes suggested that there was no fundamental difference in the perilymph response to equivalent levels of implosive versus hypobaric pressure. Three factors determined the effect of implosive and hypobaric pressure: the patency of the CA, the rate of the pressure change, and the eustachian tube function. PMID- 1598986 TI - Platform pressure test in identification of perilymphatic fistula. AB - In an effort to better define the effectiveness of the use of posturography in the preoperative diagnosis of perilymphatic fistula (PLF), a prospective investigation of the use of platform pressure posturography was performed. Six different protocols used atmospheric pressure change applied to the external auditory canal. Postural sway, monitored as the output parameter, was evaluated relative to its sensitivity and specificity in five different patient groups. Two independent surgeon groups were used to establish the final diagnosis of perilymphatic fistula. Results within a given surgeon group demonstrate varying sensitivity from 53 to 100 percent and specificity from 56 to 89 percent. Results across the two surgeon groups show nonstatistically significant changes in sensitivity and specificity, yet statistically significant differences exist between the surgeon groups for rate of surgery performed given a suspected patient group, and for rate of positive identification of PLF during surgery. We conclude that although the platform pressure test (PPT) shows promise as a test to raise preoperative suspicion for PLF, actual test performance figures cannot be calculated until a more definitive, objective, test is available to confirm the final diagnosis. The variability of selection criteria and diagnosis by surgical observation is too great to draw clear conclusions relative to test performance. Additionally, the use of vestibular rehabilitation techniques is suggested as a presurgical management strategy for a selected group of suspect patients. PMID- 1598987 TI - Effects of sample size on the latency and amplitude of the auditory evoked response. AB - Experiment I investigated the effects of sample size (500 to 1500 stimulus repetitions) on the auditory brainstem response as a function of intensity (20 to 80 dB nHL) on a group of 10 normally hearing subjects. There was little change in identifiability, reliability, latencies, or amplitudes of Waves I, III, and V as the sample size increased from 500 or 750 to 1500 repetitions. These results suggest that 500 to 750 repetitions may be adequate when methods similar to those in the present study are used, and that the common clinical practice of employing approximately 1500 repetitions may unnecessarily prolong testing. Experiment II employed 12 hearing-impaired subjects who were tested at 10 to 40 dB SL using sample sizes from 250 to 4500 stimulus repetitions. Identifiability of all waves increased as sample size increased from 250 to 4500 repetitions. The largest changes in identifiability occurred when sample size increased from 250 to 1500 or 3000 repetitions, with little improvement as sample size increased from 3000 to 4500 repetitions. Examiners should monitor averaged responses and terminate testing as soon as a wave is identified. Contrary to expectation, there was no systematic change in the standard error of measurement for latency (approximately 0.07 ms) as sample size increased from 250 to 4500 repetitions. The standard error of measurement for amplitude decreased from approximately 100 nV with 500 repetitions to approximately 45 nV at 3000 repetitions. The improvement in reliability with increasing sample size may be explained by a decrease in the variability of background noise. A systematic decrease in amplitude also was observed as sample size increased. This observation may be explained by a reduction in the residual noise levels or because of time jitter or adaptation within the auditory pathways. Nonetheless, investigators who wish to use ABR amplitude measures for diagnosis may benefit from using a relatively large sample size. PMID- 1598988 TI - Grading system for the selection of patients with congenital aural atresia. AB - It is generally recognized that surgery for congenital aural atresia is difficult. In an effort to select those patients who have the greatest chance of success, we have developed a grading scheme based on the preoperative temporal bone CT scan and the appearance of the external ear. Patients are graded on a possible best score of 10. The stapes is assigned the highest rating (2 points), while all other entrees on the scale are 1 point. The grade assigned preoperatively has been shown to correlate well with the patient's chance of success, herein defined as a postoperative speech reception threshold of 15 to 25 dB. A patient with a preoperative grade of 8/10 would, therefore, have a 80 percent chance of achieving this threshold. Patients with scores of 5/10, or less, are not considered surgical candidates, because the risk of the operation would outweigh the potential benefits. We have found that the grading system allows us to avoid impossible surgical cases while allowing for a reasonable prediction of the hearing outcome. PMID- 1598989 TI - Morphologic and electrophysiologic effects of cochlear implantation and electrical stimulation. AB - The nondeafened guinea pig model was utilized in this study to assess the functional and morphologic effects of cochlear implantation and electrical stimulation. Auditory brainstem responses (ABRs) were recorded prior to and following intrascalar implantation of a 3M-House cochlear electrode (n = 41 ears), as well as after electrical stimulation (n = 23 ears). The experimental population was divided into the following groups according to implantation and stimulation parameters: 200 microA for 3 hours (group I); 200 microA for 24 hours (group II); 400 microA for 3 hours (group III); implanted, but not stimulated (group IV); and nonimplanted, not stimulated ears (group V). Of those cochleae that sustained the trauma of implantation, 32 percent had no detectable ABR to 110 dB SPL clicks, while only 7 percent additionally failed to respond to 130 dB SPL clicks. No significant difference (one-way ANOVA with repeated measures at the 95 percent confidence limit) could be detected when comparing those ears that retained ABRs according to experimental grouping. Morphologic analysis was performed on 29 cochleae. Spiral ganglion "packing densities" were not found to be significantly different among the groups (ANOVA). The status of the organ of Corti was significantly better in groups II and V in comparison to the other groups (Kruskal-Wallis test with pairwise comparisons, p less than 0.05); there was no discernible dose-response relationship. Morphologic and electrophysiologic changes correlated with insertion trauma and infection rather than with electrical stimulation at the levels tested in this study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1598990 TI - Magnetic resonance imaging of brain herniation into the middle ear. AB - Four patients with cholesteatoma were shown to have a large area of eroded tegmen tympani on computed tomography (CT). Magnetic resonance imaging (MRI) in the coronal and sagittal plane showed temporal lobe herniation in three cases and cholesteatoma with abscess elevating the dura in one case. In the patient with a cholesteatoma and an eroded tegmen tympani on CT, MRI is indicated to rule out brain herniation into the middle ear. PMID- 1598991 TI - Posterior geniculate artery: a surgeon's guide to the facial nerve. AB - Locating the facial nerve is an essential step in most mastoid procedures. A constantly occurring, easily identifiable, arterial bleeding point has been identified arising on the posterosuperior-lateral eminence of the posterior genu of the nerve, passing posterosuperiorly. The vessel permits exact sitting of the genu before the nerve is seen, and provides a timely warning of the nerve's presence. PMID- 1598992 TI - Traumatic external auditory canal atresia. AB - Gunshot injuries in the periauricular region can result in massive tissue distortion and destruction. The soft tissue effects can be so dramatic that otologic abnormalities can be initially overlooked, especially by non otolaryngologists. Delayed stenosis or complete closure of the external auditory canal can occur. We present two cases of post-traumatic ear canal atresia that were initially overlooked by non-otolaryngologists, until secondary plastic reconstructive operations were performed in which preauricular skin incisions entered into large canal cholesteatomas. These canal cholesteatomas resulted from total obstruction of the external auditory canal after trauma. PMID- 1598993 TI - Sensorineural hearing loss associated to gonadal dysgenesis in sisters: Perrault's syndrome. AB - Genetic alterations that involve the inner ear and other systems may present well defined clinical differences. We present two oriental sisters, age 34 and 26 years, with a picture of primary amenorrhea and "infantile" uterus associated with progressive hearing loss begun in infancy in the older sister, and after 20 years of age in the younger sister. The gynecologic evaluation showed uterine hypoplasia and gonadal dysgenesis in both sisters. The audiologic study showed bilateral sensorineural hearing loss with a flat-type curve in both cases, with an average threshold of 500, 1000 and 2000 Hz (PTA) in 80 dB (older sister) and 60 dB (younger sister), with recruitment measured by stapedial reflex in the second case. Vocal discrimination was 30 percent and 80 percent, respectively. The clinical picture fits Perrault's syndrome: recessive autosomal genetic alteration, with XX gonadal dysgenesis and sensorineural hearing loss. PMID- 1598995 TI - Diagnostic and therapeutic dilemma: facial palsy attributable to basal cell carcinoma. PMID- 1598994 TI - Diagnosis and management of perilymph fistula: the University of North Carolina approach. AB - Perilymph fistula is a potentially disabling leakage of perilymphatic fluid from the otic capsule. The occurrence of perilymph fistula is now attributed to a wide variety of causes and the diagnosis is frustrated by a lack of characteristic signs or symptoms. A brief review of the literature and the University of North Carolina philosophy for the diagnosis and management of perilymph fistula is presented. Emphasis on timely evaluation and surgical technique is provided. PMID- 1598996 TI - Hemifacial spasm in the 2-year-old daughter of an otolaryngologist. PMID- 1598997 TI - Facial nerve deficits following face lift surgery. PMID- 1598998 TI - Noise-induced hearing loss: the sixth question. PMID- 1599000 TI - Electrical evaluation of the facial nerve in acoustic neuroma patients: preliminary comparison between transcranial magnetic coil stimulation and electroneurography. AB - Subclinical involvement of the facial nerve by acoustic neuromas may be identified preoperatively using conventional electroneurography (ENoG). The clinical application of extratemporal stimulation distal to the stylomastoid foramen is limited in these cases by the more proximal site of the lesion. Transcranial magnetic coil stimulation (MCS) is a noninvasive means by which the facial nerve is stimulated at the level of the motor cortex or the brain stem, before it enters the internal auditory canal. Topographically such an assessment may have more diagnostic relevance than other forms of electrical stimulation in acoustic neuroma patients. To test this theory the facial nerves of 20 patients with acoustic neuromas were stimulated using ENoG and MCS preoperatively and 1 week postoperatively. Stimulation parameters were comparable and included threshold and suprathreshold levels of stimulation while compound action potential amplitudes and early and late response latencies were monitored. Facial nerve function was assessed clinically using the Stennert grading system. All the patients had clinically normal facial nerve function preoperatively. Normative data suggested a close correlation between threshold and suprathreshold amplitudes generated by both ENoG and MCS. To the contrary, in the pathologic ears there was a higher incidence of stimulus response abnormality determined by MCS than by ENoG. A comparison of these data, tumor size, and postoperative results promotes further evaluation of MCS as a prognostic index in acoustic neuroma patients. PMID- 1598999 TI - Motility of cochlear outer hair cells. AB - A recent exciting discovery in the physiology of hearing has been that fine tuning and regulatory properties of the mammalian auditory system reside in the micromechanics of the basilar membrane. While the inner hair cells are considered primary afferent transducers, the outer hair cells are postulated to modulate transduction based on their motile properties. These new insights have impacted on our view of auditory processing and are also leading to improved diagnostic procedures (such as those based on otoacoustic emissions) and a better understanding of sensorineural pathology. Outer hair cell motility may be separated into two categories: fast and slow. Fast motility is voltage-driven and frequency-following and provides positive feedback to the motion of the basilar membrane. Slow motility (shape changes measured in milliseconds to seconds) can be triggered through depolarization by potassium, osmotic effects, mechanical stimulation, efferent neurotransmitters, and the elevation of intracellular second messengers and calcium ions. These slow changes may be superimposed upon the fine-tuning provided by the fast motility. This paper discusses the mechanism underlying the shape changes induced by different stimuli, and assesses the role of fast and slow motility in the physiology and pathology of auditory transduction. PMID- 1599001 TI - Effects of channel number and place of stimulation on performance with the Cochlear Corporation multichannel implant. AB - The effects of active channel number and place of stimulation on auditory-only performance with the Cochlear Corporation multichannel cochlear implant were investigated in seven subjects. A balanced crossover design was employed; subjects were initially programmed with either 10 basal or the full complement of 20 to 21 active electrodes. Following a 6-month period with the initial coding strategy, subjects were programmed with the alternate configuration, which they used for an additional 6 months. Auditory-only performance on suprasegmental, phoneme (vowel and consonant) open- and closed-set speech recognition was compared between the two electrode configurations. Additionally, performance with the first configuration and performance with the second configuration 3 days following programming were also compared. While a trend for increased scores was noted with 20 electrodes, especially with open-set speech recognition tasks, none of the differences between the two configurations reached statistical significance, as indicated by a Wilcoxon test. A comparison of performance at the end of the first 6-month period and 3 days following programming with the second configuration revealed a trend for reduced scores, especially on vowel tests. Overall, our results indicate that the feature extraction coding strategy associated with the Cochlear Corporation device allows patients to function well with only 10 basal electrodes and that speech recognition is only mildly affected initially when patients are programmed with a different encoding strategy. PMID- 1599002 TI - Myths in neurotology. AB - For many diseases the etiology of disordered function is unknown and therapy is either symptomatic or empirical. The empirical approach to therapy is acceptable to many physicians, particularly if a treatment can be based on some attractive, although unproven, concept of pathogenesis. A hypothetical explanation of disordered function can become widely popular in spite of a serious lack of scientific support. When evidence emerges that refutes the logic of a concept of pathogenesis, then that concept becomes a myth. Human temporal bone studies have identified several myths in neurotology that deserve our attention. Among these myths are the following: (1) cochlear otosclerosis is a common cause for sensorineural hearing loss, (2) idiopathic sudden sensorineural hearing loss is a vascular disorder that should be treated as a medical emergency, (3) the conductive component of hearing loss in Paget's disease is caused by ossicular fixation and therefore should be surgically correctable, (4) vascular loops should be considered as a possible cause for otherwise unexplained otologic symptoms, (5) surgical manipulations on the endolymphatic sac are scientifically sound therapies for selected cases of Meniere's disease, and (6) perilymph fistulas are a common cause for audiovestibular symptoms that are not related to a stressful incident. PMID- 1599003 TI - Correlation of the nerve excitability test and electroneurography in acute facial paralysis. AB - In a retrospective study of 77 patients with acute facial palsy, the results of the nerve excitability test (NET) and electroneurography (ENoG) were analyzed in order to establish a mathematic correlation and to relate the prognostic NET values to quantitative ENoG results. The two tests are related by exponential functions. Coefficients of correlation were higher for the results between NET and the optimized lead placement (OLP) ENoG compared to NET and standardized lead placement (SLP) ENoG. The highest correlation coefficients were demonstrated when NET was performed over the marginal and zygomatic branches of the facial nerve and OLP ENoG recorded in the nasolabial region. Good prognostic NET threshold differences in patients with a small percentage of intact motor axons, calculated by ENoG, may represent segmental demyelination or the deblocking phase of neuropraxia. The tests are complimentary in establishing the integrity of the facial nerve in acute paralysis. PMID- 1599005 TI - Indications for hearing preservation in acoustic tumor surgery. AB - This study addresses the problem of how to counsel patients with acoustic tumors concerning the issue of hearing preservation. Rather than the traditional yes or no answer, we wish to give the patient the probability that hearing can be preserved given the size of the tumor and the patient's preoperative hearing level. The subjects were 77 patients of the Seattle Ear Clinic who underwent total removal of unilateral acoustic tumors with attempted hearing preservation using a suboccipital approach. Other criteria for inclusion in the study were: tumor size, measured from a preoperative diagnostic image, and availability of pre- and postoperative hearing test results. We reviewed published data from other centers using similar inclusion criteria to determine if our findings were representative of the experience of surgeons at other institutions. We found a significant relationship between hearing preservation success and tumor size, but not between success and preoperative hearing level. The probability of success varied from 78 percent for 0.5-cm tumors to about 15 percent for tumors 2.0 cm and larger. If surgery was successful, 82 percent of patients had hearing that was the same or better than their preoperative hearing level. PMID- 1599004 TI - Long-term hearing results in patients after surgical removal of acoustic tumors with hearing preservation. AB - Long-term hearing results are described in 18 patients after suboccipital removal of unilateral acoustic neurinomas. Follow-up ranged from 3.4 to 10.4 years with a mean of 5.4 years. Fourteen patients (78%) experienced no significant decline in long-term hearing. Four patients (22%) experienced a significant decline in long term hearing as defined by a drop in pure-tone average (0.5, 1, and 2 kHz), or a significant decline in Speech Discrimination Scores (SDS). Changes in hearing did not correlate with tumor size, preoperative hearing, intraoperative change in hearing, the interval between initial symptoms and surgery, sex, or age. PMID- 1599006 TI - Computer-aided three-dimensional reconstruction and measurement of microfissures. AB - The spatial anatomy of microfissures in the round and oval window areas was investigated in 24 randomly selected normal human temporal bones by our computer aided three-dimensional reconstruction and measurement method. Microfissures that communicated with the middle ear surface in the round window area were seen in 21 cases (87%) and were located on the posteromediosuperior aspect of the round window niche; whereas microfissures in the oval window area, seen in seven cases (29%), were located at various sites, but mostly in the area below the oval window. Of the 21 microfissures seen in the round window niche, only four were found to be visible through the aperture of the round window niche when viewed from the lateral direction. The mean lengths of the microfissures seen on the middle ear surface in the round and oval window areas were 0.95 +/- 0.66 mm and 0.74 +/- 0.44 mm, respectively. The microfissures in the round window area were significantly longer in individuals 20 years of age and older, than in those less than 20 years (Wilcoxon test, t = 21.5, p less than 0.01); this tendency for microfissures to be longer in older subjects was also found for microfissures in the oval window area. The possible clinical and pathologic significance of these results is discussed. PMID- 1599007 TI - Electrocochleography in the diagnosis of perilymphatic fistula: intraoperative observations and assessment of a new diagnostic office procedure. AB - The intraoperative electrocochleogram (ECochG) was investigated during stapedectomy surgery and during cochleostomy surgery. This provided the justification for obtaining recordings with the oval window (OW) or round window (RW) intact and then when there was a definite fistula. It was noteworthy that no ECochG changes occurred on merely opening the OW or RW, but that marked changes occurred on removing perilymph, even by gentle suction. On raising the intrathoracic pressure and replacing the perilymph, the ECochG potentials usually recovered. Based on these intraoperative observations, an office procedure was designed. The subject was asked to raise the intrathoracic pressure on several occasions and changes in the amplitude of the ECochG potential were noted. An increase of over 15 percent in the action potential (AP), with or without a decrease in the negative summating potential (SP) during the period of raised intrathoracic pressure, was used as the diagnostic criteria for a perilymphatic fistula. A decrease in the AP with or without an increase in the negative SP immediately on relaxing after a period of raised intrathoracic pressure was also treated as a positive diagnostic criterion. Seventy-one normal ears were investigated and a positive result was recorded in two ears (false positive rate: 2.8%). Two hundred and six ears, strongly suspected as having a perilymph leak on the basis of the clinical history and vestibular signs have been investigated over the past 4 years. Ninety positive diagnoses have been reached and 46 of these ears have been surgically explored.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599008 TI - Clinical implications of otolith-ocular reflexes. AB - While difficult to test clinically, otolith-induced vestibular responses play an important role in both vestibulo-ocular and vestibulo-spinal reflexes, and are likely a source of symptoms in patients with vestibular disorders. Here we review basic aspects of otolith-induced vestibulo-ocular reflexes and consider some clinical implications of disordered otolith function. Emphasis is placed on ocular responses to translation and to tilt and the influence of gravity on vestibulo-ocular responses induced during head rotation. PMID- 1599009 TI - Treatment and management of perilymphatic fistula: a New Hampshire experience. AB - From August of 1975 to June of 1990 the author managed 45 cases of spontaneously occurring perilymphatic fistula. Twenty-nine of the 45 cases were reported in 1988. In the series there were eight patients with bilateral involvement, seven with involvement of both oval and round window in the same ear, and seven with fistulas believed to be of congenital origin. Seventeen patients (38%) required revision surgery. Occasionally adjunct modalities (endolymphatic shunt, labyrinthectomy, blocking a cochlear aqueduct, and streptomycin ablation) were used for symptom control. Diagnosis, treatment, and management of these patients is discussed. PMID- 1599010 TI - Facial paralysis in temporal bone trauma. AB - A retrospective review of 36 patients with delayed-onset (19 patients) and immediate-onset (17 patients) traumatic facial paralysis was performed. We hypothesized that traumatic delayed-onset facial paralysis does not necessitate surgical decompression under any routine circumstances. Of 19 patients in this group, normal recovery (House grade 1) occurred in 94 percent of the patients without surgical intervention. The small percentage (6%) of these patients who failed to recover completely demonstrated mild degrees of weakness and synkinesis (House grade 2). Immediate-onset paralysis occurred in 17 patients. It has a much poorer prognosis. Seven patients with penetrating wounds had facial nerve transections, usually of the vertical portion of the facial nerve. Closed head injured patients with immediate-onset facial paralysis sustained injuries usually to the horizontal and perigeniculate portion of the facial nerve. For those cases in which surgical exploration of the traumatized facial nerve is indicated, the operating surgeon should have the capacity to enlarge the exposure with a translabyrinthine or middle-fossa dissection. PMID- 1599011 TI - Survival and evolution of vein grafts in otosclerosis surgery: structural and ultrastructural evidence. AB - The annular ligament of the stapes footplate measures 0.2 mm2 and contains elastic fibers that restrict perilymphatic movement to a molecular level. This resistance of the annular ligament prevents excessive movement of labyrinthine fluids that are potentially hazardous to the membranous and cellular structures of the inner ear. However, if the resistance of the annular ligament is overcome, then inner ear damage can occur. The vein graft, as used in our technique for otosclerosis surgery, occupies a space of 0.2 mm2 between the edge of the stapedotomy hole and the piston and has nearly the same compliance and resistance as the annular ligament of the stapes footplate. The vein graft becomes integrated with the middle-ear mucosa. It develops a rich and active blood supply and the smooth muscle cells and elastic fibers remain, although the latter show some modification of ultrastructural pattern. The graft becomes overlaid by the middle-ear epithelium. Even samples of vein graft that have been present for many years retain surviving elastic fibers, including those that have become fibrotic. In time, the number of elastic fibers increases as a result of the activity of fibroblasts, which build a poorly colored collagen. PMID- 1599012 TI - Primary malignant melanoma of the external auditory canal: a case report with presentation as an aural polyp. AB - A case of primary cutaneous melanoma of the external auditory canal and a review of the literature are reported. This is the first reported case with microstaging of the tumor. The tumor presented as a polypoid obstructive lesion of the external ear canal. Although occurrence of melanoma in this location is extremely rare, differential diagnosis of an external ear canal polyp should be expanded to include primary malignant melanoma. PMID- 1599013 TI - Computerized quantitative dynamic analysis of facial motion in the paralyzed and synkinetic face. AB - Diagnosis, treatment, prognosis, and the neurobiology of recovery of facial paralysis has been impeded by the inability to quantitate facial movement objectively. The purpose of this paper is to report our preliminary results in the study of the paralyzed face using a newly developed computerized quantitative dynamic analysis system. Five normal volunteer subjects, and 17 patients with facial paralysis or paresis, from a wide range of etiologies, were analyzed utilizing the computerized analysis system; eight of these patients had synkinesis. Raw data image-change intensity: duration curves, numeric and graphic displays of curve parameter descriptive statistics, and rank order correlation analyses showed high levels of correlation between the computerized facial motion analysis and the House-Brackmann facial nerve grading system and a clinical grading scale for synkinesis. These data suggest that it is possible to develop a computerized image-difference analysis system that approximates the human ability to access facial movement and, additionally, deliver an equal-interval continuous quantitative data scale dynamic over a spectrum of time during facial motion. PMID- 1599014 TI - Spindle cell rhabdomyosarcoma. A prognostically favorable variant of rhabdomyosarcoma. AB - Twenty-one cases of embryonal rhabdomyosarcoma, composed mainly of elongated spindle cells arranged in a fasciculated or storiform pattern, were retrieved from the files of the German-Italian Cooperative Soft Tissue Sarcoma Study. The term spindle cell rhabdomyosarcoma is proposed to designate this histotype. Spindle cell rhabdomyosarcoma predilected male patients (18 males, three females) and involved mostly the paratesticular area (12 cases) and the head and neck region (six cases). Histologically, all cases were characterized by a uniform proliferation of elongated spindle cells with eosinophilic and fibrillar cytoplasm mimicking smooth muscle fibers; immunocytochemical studies disclosed high expression of the muscle markers titin, desmin, and myoglobin. Clinical information was available in 17 cases; according to the Intergroup Rhabdomyosarcoma Study (IRS) grouping system, 13 were classified in group I, two in group II, and two in group III. Sixteen patients were well and alive 24 to 100 months after diagnosis; one patient died from disease progression 24 months after diagnosis. Analysis of our results determined that spindle cell rhabdomyosarcoma constitutes a rare variant of the embryonal form, showing a high degree of skeletal muscle differentiation and a low malignant potential; it should therefore be distinguished from classical forms of embryonal rhabdomyosarcoma. PMID- 1599015 TI - T-cell lymphoblastic lymphoma with eosinophilia associated with subsequent myeloid malignancy. AB - Three patients with T-cell lymphoblastic lymphoma and peripheral blood eosinophilia are reported. At the time of diagnosis, all patients had lymphadenopathy, and one had a mediastinal mass. Lymph node biopsies revealed lymphoblastic lymphoma admixed with a variable number of mature eosinophils. Immunophenotypic studies demonstrated that each lymphoma had an immature T-cell immunophenotype. Bone marrow biopsies were hypercellular with myeloid hyperplasia and eosinophilia but were negative for lymphoma. All patients received multiagent chemotherapy; one patient achieved a complete remission, and two patients had partial remissions. All patients subsequently developed a myeloid malignancy. Two died of acute myeloid leukemia within 18 months of the diagnosis of lymphoblastic lymphoma. The third patient relapsed with a lymphoma that had histologic and immunophenotypic features of both T-cell lymphoblastic lymphoma and granulocytic sarcoma and also developed a poorly defined myeloproliferative disorder. These findings suggest that T-cell lymphoblastic lymphoma associated with eosinophilia may represent a distinct clinico-pathologic entity with a high risk of subsequent myeloid neoplasia. PMID- 1599016 TI - Atypical duct hyperplasia of the breast in young females. AB - Atypical duct hyperplasia of the breast is an unusual finding in the adolescent or young adult female. We report nine young women, ages 18-26 years (mean 21) with atypical duct hyperplasia. Clinical presentation was either breast hypertrophy treated by reduction mammoplasty (five patients) or a thickening or mass that was examined via biopsy (four patients). No focal abnormalities were present on gross examination other than two fibroadenomas in one patient. Microscopically, isolated hyperplastic ducts were scattered in a background of prominent stromal collagenization. Each case showed a continuum of ductal changes, from partial to complete involvement by micropapillary and laciform epithelial hyperplasia, which was sometimes markedly atypical. In four, lobules were poorly developed or not present in the available sections. During a follow up of 5-68 months (mean 39), none developed breast carcinoma. Much longer follow up is needed to determine if young women with atypical duct hyperplasia are at increased risk for subsequent development of breast carcinoma. Presently, no surgical or medical intervention is recommended, but such patients should perform breast self-examination and be monitored regularly by a physician. PMID- 1599017 TI - Florid progressive transformation of germinal centers. A syndrome affecting young men, without early progression to nodular lymphocyte predominance Hodgkin's disease. AB - Progressive transformation of germinal centers (PTGC) occurs focally in reactive lymph nodes, and has been reported with increased frequency in patients with nodular lymphocyte predominance Hodgkin's disease (NLPHD). It has been suggested that patients with lymph node biopsy samples showing PTGC are at increased risk for the development of NLPHD, and that Hodgkin's disease may evolve from PTGC. We report five young men (ages 14-24 years, mean 18) with prominent lymphadenopathy and florid PTGC, in whom careful examination and follow-up showed no progression to Hodgkin's disease. Three patients developed adenopathy that involved several node groups and two had localized adenopathy. Cervical (2), inguinal (2) and axillary (1) nodes ranging from 3 to 4 cm were excised. The number of progressively transformed germinal centers (PTGCs) ranged from 10 to 123 per specimen (mean 67); single sections contained nine to 29 PTGCs (mean 19). In three cases the nodal architecture was significantly distorted, suggestive of NLPHD, but Reed-Sternberg cells were absent. Follow-up is available for all patients (all untreated): three patients had persistent adenopathy 1 year 4 months to 10 years after diagnosis. Results of repeat biopsy in two patients (2 and 3 years after diagnosis) showed florid PTGC with no evidence of Hodgkin's disease. One of these patients had one subsequent biopsy 8 years after presentation; results showed only rare PTGCs. The fourth and fifth patients, who had presented with isolated adenopathy, were free of recurrent adenopathy at 2 and 5 years. These cases suggest a syndrome of lymphoid hyperplasia with florid PTGC in adolescent boys and young men. Although adenopathy can persist, there has been no progression to Hodgkin's disease. Recognition of this syndrome is important to avoid overdiagnosis of LPHD. Close follow-up of these patients will be necessary to evaluate the relationship of this disorder to NLPHD. PMID- 1599018 TI - Monoclonal antibody K1 reacts with epithelial mesothelioma but not with lung adenocarcinoma. AB - Immunoperoxidase histochemical staining of cryostat sections from human tumor tissues revealed that a murine monoclonal antibody (MAb), K1, can distinguish epithelial mesotheliomas from lung adenocarcinomas. All of 15 epithelial-type mesotheliomas and all four mixed type mesothelioma samples, but none of 23 lung adenocarcinomas with different degrees of histologic differentiation demonstrated reactivity with antibody K1. Of the cell populations in each mesothelioma tested, 80% to 100% showed strong and homogeneous staining with MAb K1. Immunofluorescence analysis of live cultured cells from an epithelioid mesothelioma (H-meso) and several lung carcinoma cell lines as well as a pleural effusion of a patient with mesothelioma also showed selective reactivity of K1 with the mesothelioma cells. These data indicate that K1 can be useful as a mesothelial cell marker for the differential pathological diagnosis of the epithelial form of mesothelioma; K1 may also be useful in the study of the pathogenesis, immunodiagnosis, and immunotherapy of epithelial-type and mixed type human malignant mesothelioma. PMID- 1599019 TI - Cortical osteofibrous dysplasia of long bone and its relationship to adamantinoma. A clinicopathologic study of 30 cases. AB - Thirty cases of cortical osteofibrous dysplasia (COFD) were studied in an attempt at defining the relationship of COFD to adamantinoma. The patients ranged in age from newborn to 39 years (mean 13.4 years). The male:female ratio was 1:1. Presenting symptoms were most often pain or a mass. The tibia was involved in all 30 patients; in addition, the ipsilateral fibula was involved in five patients (17%). The histologic appearance of the lesions was dominated by the combination of woven bone trabeculae with prominent osteoblastic rimming and a loose, slightly myxoid stroma (less heavily collagenized in most instances than usually encountered in intramedullary fibrous dysplasia). Results of immunohistochemical study showed isolated cytokeratin-positive cells in the stroma of 28 of the lesions (93%). However, hyperchromatic epithelial islands characteristic of adamantinoma were not found in any of the 30 cases. A control population of 50 fibro-osseous lesions (intramedullary fibrous dysplasia, sclerosing fibroxanthoma, and cranial ossifying fibroma) was studied immunohistochemically; in none of these control cases were cytokeratin-positive cells found. Follow-up data were obtained in 17 cases (57%); the period ranged from 1 to 16 years (mean 6.05 years). Certain overlapping clinical features (including the location of the vast majority of the lesions in the tibia and, less often, the fibula) and the morphologic similarities of many areas of COFD and adamantinoma (particularly the shared presence of cytokeratin-positive cells) suggest a more than coincidental association between COFD and a adamantinoma. However, to date none of the 30 cases of COFD evaluated in this study has developed an adamantinoma. PMID- 1599020 TI - Desmoplastic small round-cell tumor. PMID- 1599021 TI - PEC and sugar. PMID- 1599022 TI - Pseudovascular adenoid squamous cell carcinoma of the skin. A neoplasm that may be mistaken for angiosarcoma. AB - The adenoid variant of squamous cell carcinoma has been well-documented in several anatomic sites, including the skin. This tumor is characterized by acantholytic arrays of neoplastic keratinocytes that form pseudoglandular profiles. Although it is typically confused with adenocarcinomas, adenoid squamous cell carcinoma also may be mistaken for malignant vascular proliferations. This report concerns six acantholytic cutaneous squamous cell carcinomas that closely simulated angiosarcomas on conventional histologic examination. They arose in sun-exposed skin areas in middle-aged or elderly patients (mean age, 60 years), five of whom were men. In contrast to the typical clinical appearance of angiosarcoma, pseudovascular adenoid squamous cell carcinoma presented itself as a discrete cutaneous ulcer or crusted tanpink nodule. Microscopically, this lesion was characterized by interanastomosing cordlike arrays of polygonal or flattened tumor cells, with internal pseudolumina that contained detached tumor cells. A connection between the dermal neoplasm and the epidermis was apparent in three cases, but it was focal. Erythrocytes were seen in pseudovascular spaces in five tumors. Immunohistochemically, all examples of pseudovascular adenoid squamous carcinoma were reactive with antibodies to cytokeratin and epithelial membrane antigen (EMA). In addition, three expressed vimentin, two exhibited blood group antigen-positivity, and two bound Ulex europaeus I agglutinin. None of them was immunoreactive for Factor VIII-related antigen, and two of three studied for CD34-reactivity were likewise negative. A control group of six cutaneous angiosarcomas was uniformly nonreactive for cytokeratin and EMA, but they showed positivity for vimentin, Ulex binding, and CD34 positivity in all instances. Pseudovascular adenoid squamous cell carcinoma may be distinguished effectively from angiosarcoma of the skin by attention to its clinical features and by appropriate immunohistochemical studies. These two tumors differ in biologic behavior; three patients with pseudovascular adenoid squamous cell carcinoma died of their tumors, whereas all angiosarcomas in this series proved fatal. PMID- 1599023 TI - Pseudosarcomatous myofibroblastic proliferations of the spermatic cord ("proliferative funiculitis"). Histologic and immunohistochemical analysis of a distinctive entity. AB - Pseudosarcomatous myofibroblastic proliferations have been recognised at a variety of sites. We describe five lesions of the spermatic cord, four of which were incidental findings at inguinal herniorrhaphy. The patients' age range was 52-76 years. In all cases, sarcoma was suspected histologically, but each lesion showed morphologic features in keeping with fasciitis-like lesions described at other sites. Two cases showed actin positivity, supporting this interpretation. All were marginally or incompletely excised. One recurred locally. We believe that ischemia or torsion is of pathogenetic importance at this site. We propose that the term "proliferative funiculitis" be used to describe this type of reactive process when it presents in the spermatic cord. PMID- 1599025 TI - Peritoneal serous micropapillomatosis of low malignant potential (serous borderline tumors of the peritoneum). A clinicopathologic study of 17 cases. AB - Primary peritoneal serous micropapillomatosis of low malignant potential, or serous borderline tumor of the peritoneum, is a relatively rare lesion that is histologically indistinguishable from peritoneal "implants" associated with ovarian papillary serous tumors of low malignant potential. We analyzed 17 cases to further define the pathologic features and prognosis of this entity. The ages of the patients ranged from 16 to 67 years (mean, 33 years). Eight patients were symptomatic with chronic pelvic or abdominal pain (five patients), adnexal mass (one patient), small-bowel obstruction (one patient), and possible endometriosis (one patient). In nine cases (53%), peritoneal serous micropapillomatosis of low malignant potential was an incidental finding discovered during evaluation or treatment of other conditions. Grossly, the peritoneal lesions were focal or diffuse. They commonly appeared as miliary granules and often were believed to be peritoneal carcinomatosis. Microscopically, peritoneal serous micropapillomatosis of low malignant potential had all of the patterns seen in superficial ("noninvasive") peritoneal implants of ovarian serous borderline tumors. Psammoma bodies were a prominent feature of all cases. Twelve patients also had typical endosalpingiosis. Most patients were treated by hysterectomy and bilateral salpingo-oophorectomy. Surgical treatment in seven patients consisted only of biopsy. Ten patients had residual unresected disease at the time of their initial operation. Several patients received adjuvant chemotherapy. Follow-up was available for 14 of the 17 patients. One patient died of metastatic breast carcinoma at 3.8 years; another patient died 7 weeks after operation, possibly as a complication of therapy. The other 12 patients were alive at last known contact after follow-up intervals of 8 months to 16.2 years (mean, 7.5 years). Two of these 12 patients developed multiple episodes of small-bowel obstruction due to persistent peritoneal serous micropapillomatosis of low malignant potential; neither received adjuvant chemo- or radiotherapy. Both were alive without progressive disease 10.9 and 16.2 years after initial diagnosis, respectively. This excellent prognosis supports a regimen of conservative therapy for these patients. PMID- 1599024 TI - Splenic marginal zone cell lymphoma. AB - We describe four female patients with primary splenic low-grade non-Hodgkin's B cell lymphomas with the morphology and immunophenotype of splenic marginal zone lymphocytes. The patients presented with splenomegaly, anemia, and weight loss. The bone marrow was involved in all four cases. Liver involvement was found in one patient; and in another, a CT scan revealed lymphadenopathy in the chest and abdomen. The histology of the spleen was characterized by broad concentric strands of monomorphic medium-sized lymphocytes around lymphoid follicles in one case and infiltrating follicles in two cases. Selective replacement of follicles was seen in one case. Tumor in splenic hilar lymph nodes (four cases) and liver (one case) was similar. Three patients remain well 4, 9, and 12 months, respectively, after splenectomy without further treatment. One patient who received chemotherapy died 1 year after splenectomy. PMID- 1599026 TI - Local audit of surgical pathology. 18 month's experience of peer review-based quality assessment in an English teaching hospital. AB - In order to assess the performance of a surgical pathology laboratory in a university hospital, we have established a comprehensive system of quality audit based on peer review. Each month, 2% of cases received are selected at random and assessed retrospectively by two senior pathologists. The system, which uses semi quantitative scoring, examines diagnostic accuracy, identifies delay at any stage in the production of reports, evaluates the overall quality of the slides, the presentation of the final report, and the accuracy of the SNOMED coding. Each of these parameters is graded as "satisfactory," "borderline," or "unsatisfactory." In 20 of 518 cases (3.9%) analyzed in 18 months, the microscopic report was unsatisfactory; in six of these cases, the error could have affected patient management. Remediable faults were detected in the macroscopic description of specimens and in the speed and accuracy of report typing by the secretarial staff. In 13 of 18 months, greater than 10% of reports were delayed because of the time taken in microscopic reporting by pathologists. Some (but not all) of this delay was attributable to the "checking out" of pathologists in training. We conclude that this audit system has uncovered substantial deficiencies in our departmental performance, some of which could affect the clinical course of patients. These surprising results suggest that a system of peer review should be adopted more widely. PMID- 1599027 TI - Desmin positivity in primitive neuroectodermal tumors of childhood. AB - In this report, we describe two rosette-forming primitive neuroectodermal tumors that were found to contain desmin by both immunohistochemistry and Western blotting. Electron microscopy on both cases was consistent with primitive neuroectodermal tumors and revealed that the tumor cells contained cytoplasmic bundles of intermediate filaments. In both cases, studies for MyoD1 protein using immunohistochemistry and Western blotting were negative. Thus, the detection of desmin in a pediatric neoplasm does not absolutely exclude the diagnosis of primitive neuroectodermal tumor and should not be considered as prima facie evidence that a small-cell tumor is a rhabdomyosarcoma. PMID- 1599028 TI - Transitional cell carcinoma with rhabdoid features. AB - We discuss the light-microscopic, immunohistochemical, electron-microscopic, and flow cytometric analysis in a case of invasive transitional cell carcinoma of the renal pelvis with rhabdoid features and glandular metaplasia. This tumor demonstrated in situ rhabdoid transformation of the transitional epithelium, which has not been described before. Electron-microscopic examination of the rhabdoid cells revealed whorled aggregates of intermediate filaments. There was also evidence of mucin-filled intracellular lumina on light and electron microscopy in both in situ and invasive components of the tumor. Our findings lend support to the view that tumors with "rhabdoid" features in adults and perhaps some children represent a heterogeneous group of neoplasms, some of which may just be unusual morphologic variants of a transitional cell carcinoma, in contrast to the distinct clinicopathologic entity of childhood renal rhabdoid tumors. PMID- 1599029 TI - Pseudotuberculous pyelonephritis associated with nephrolithiasis. AB - This report describes a 40-year-old man with an unusual form of granulomatous pyelonephritis, associated with nephrolithiasis, resulting in end-stage kidney disease and right pretransplant nephrectomy. The kidney specimen contained a staghorn calculus and showed chronic inflammation with confluent caseating granulomas and multinucleated giant cells, resembling renal tuberculosis. However, neither tubercle bacilli nor other microorganisms were demonstrated in the renal tissue or in urine cultures. Because these findings do not support a tuberculous etiology of the granulomatous pyelonephritis, we conclude that this patient had a pseudotuberculous reaction as a consequence of nephrolithiasis. PMID- 1599030 TI - Prostatic acid phosphatase in cloacal derivatives. PMID- 1599031 TI - Sponge artefacts. PMID- 1599032 TI - Sponge artefacts. PMID- 1599033 TI - Sponge artefacts. PMID- 1599035 TI - Hemangiomas of the breast with atypical histological features. Further analysis of histological subtypes confirming their benign character. AB - Eighteen patients with vascular tumors of the breast that exhibited characteristics raising the question of but not qualifying for a diagnosis of low grade angiosarcoma were reviewed. We had previously referred to these lesions as "atypical" hemangiomas because of concern regarding the diagnosis and the risk of the later development of angiosarcoma. Significant features, variably present, included small size (less than 2.0 cm), relative circumscription, broadly anastomosing vascular channels, and endothelial hyperplasia. Destructive invasion, solid areas, and hemorrhage or necrosis unrelated to a needle localization procedure were absent. Four distinct histological patterns were observed: cavernous, compact capillary, capillary budding, and a combined cavernous and compact capillary type. The age of the patients varied from 19 to 82 years (mean 60 years). Eleven tumors were detected mammographically. The size of the lesion ranged from 0.4 to 2.0 (mean 0.9) cm. The diagnostic biopsy was the only treatment in nine (50%) cases. Reexcision was performed in seven and mastectomy was done in two cases. Follow-up ranged from 1 to 140 (mean 44) months. There have been no local or systemic recurrences. Hemangiomas with diverse histological patterns have been detected clinically with the increasingly widespread use of mammography. Further follow-up indicates that the lesions originally referred to as "atypical" are benign and not associated with an appreciable risk of the development of angiosarcoma. Complete excision alone is recommended to treat these tumors, which may be diagnosed as hemangiomas and subclassified according to growth pattern. PMID- 1599034 TI - Clinicopathologic and immunologic features associated with transformation of mycosis fungoides to large-cell lymphoma. AB - Mycosis fungoides (MF) can progress to a large-cell malignant lymphoma (LCL). This transformation is associated with a more aggressive biologic behavior and course. We reviewed cutaneous tumors of 36 MF patients and divided them into two groups, one showing histologic evidence of transformation into LCL, another characterized by infiltrates of small- to medium-sized cerebriform cells (nontransformed cases). Biopsies of patches or plaques from early MF stages were available from 34 patients. Twenty of the 36 cases (55.6%) showed transformation to a large-cell variant: nine tumor-stage (T) medium-sized and large-cell pleomorphic, five T immunoblastic, two T large-cell anaplastic, and four unclassified T LCL. Sixteen cases represented nontransformed tumor stage MF. In 23 cases, including both nontransformed (n = 6) and LCL (n = 17) groups, immunohistochemical investigations revealed aberrant patterns of antigen expression (partial loss of one or more T cell-associated antigens) and the presence of activation- and proliferation-associated antigens. Clusters of B lymphocytes formed a distinctive component of the infiltrate in two nontransformed and nine LCL biopsies. Although survival rates after tumor onset did not significantly differ between the two groups (5-year survival rate 23% for nontransformed patients, 11.1% for LCL patients, p greater than 0.05), overall survival from first biopsy diagnostic of MF showed a statistically significant difference between patients with nontransformed tumor stage MF compared with LCL patients (10-year survival rate 46.6% and 11.2%, respectively, p less than 0.02). The recognition of transformation to LCL in MF should provide a better assessment of future therapeutic approaches. PMID- 1599036 TI - Ovarian serous tumors of low malignant potential (serous borderline tumors). The relationship of exophytic surface tumor to peritoneal "implants". AB - A series of 98 ovarian serous tumors of low malignant potential (LMP) was studied to test the validity of the implantation theory of extraovarian peritoneal spread of tumor by assessing the association between exophytic tumor on the ovarian surface and synchronous peritoneal implants. Patient's ages ranged from 17 to 77 years (mean, 37.8 years). The ovarian tumors were bilateral in 39 cases (40%). Exophytic tumor was present in 47 (48%) cases and involved at least one ovary in 82% of bilateral tumors. Exophytic tumor was found in 29 of 31 patients (94%) with peritoneal implants, but in only 18 of 67 patients (27%) without peritoneal implants. Moreover, 29 of 47 patients (62%) with exophytic tumor had peritoneal implants compared with only 2 of 51 patients (4%) without exophytic tumor. The utility of exophytic tumor as a marker of synchronous peritoneal implants had a diagnostic sensitivity of 94%, a diagnostic specificity of 73%, and an efficiency of 80%. Because of the strongly positive correlation between exophytic tumor and peritoneal implants, the implantation theory remains as a highly likely explanation for extraovarian spread of ovarian serous LMP tumors. The multicentric "field effect" theory, however, cannot be entirely excluded and may be operative in some cases. PMID- 1599037 TI - Immunoreactivity for BER-EP4 in adenocarcinomas, adenomatoid tumors, and malignant mesotheliomas. AB - Ber-EP4 is a recently characterized monoclonal antibody directed against a cell surface glycoprotein that is putatively present on human epithelial cells but lacking on the mesothelium. To investigate the diagnostic efficacy of Ber-EP4 in distinguishing adenocarcinoma from mesothelioma, we studied formalin-fixed, paraffin-embedded sections from well-documented cases of adenocarcinoma (120 cases), adenomatoid tumor (nine cases), and malignant mesothelioma (49 cases). Of the 120 adenocarcinomas, 103 (86%) showed membranous Ber-EP4 positivity, with diffuse reactivity noted in 82 cases and focal staining in 21 cases. Reactivity with Ber-EP4 was also observed in two of nine adenomatoid tumors (22%) and 10 of 49 mesotheliomas (20%). Staining in the mesotheliomas was restricted to epithelioid areas and generally focal. In one mesothelioma, however, Ber-EP4 stained the majority of neoplastic cells. In contrast to previous reports, we conclude that positivity with Ber-EP4 does not exclude the diagnosis of mesothelioma. Nonetheless, most Ber-EP4-positive mesotheliomas exhibit only focal positivity, as opposed to the extensive staining commonly observed in adenocarcinomas. Ber-EP4 has diagnostic utility in the discrimination of mesothelioma from adenocarcinoma, but it is best utilized in an antibody panel that includes other markers of carcinomatous differentiation. PMID- 1599038 TI - Uterine serous carcinoma. A morphologically diverse neoplasm with unifying clinicopathologic features. AB - This study compares the clinicopathologic features of 13 pure uterine papillary serous carcinomas (UPSC) with 19 tumors consisting of UPSC admixed with other types of endometrial carcinoma and nine UPSC associated with endometrial polyps. The mean patient age, frequency of preoperative clinical understaging, postoperative pathologic stage, and survival of patients was similar for the three groups. Surprisingly, widespread metastasis, recurrence, and death occurred even in those cases where myometrial invasion amounted to less than 1 mm or where tumor was confined to an endometrial polyp. Poor prognosis appeared to be related to a propensity for vascular invasion and multifocal carcinogenesis. The latter was manifested by the presence of cytologically malignant cells closely resembling the invasive serous carcinoma in the surface endometrium adjacent to the tumor in 89% of cases and in multiple sites in the genital tract and abdomen. This lesion, designated "intraepithelial carcinoma," was present in the endocervix in nine (22%) of the 41 cases, in the fallopian tube in two cases (5%), on the surface of the ovary in four cases (10%), and on peritoneal surfaces or omentum in 10 cases (25%). In addition, we found that UPSC display considerable morphologic heterogeneity. Foci of clear-cell carcinoma were identified in 13 (32%) of the 41 tumors. In five (12%) neoplasms, the invasive component was composed primarily of glands; and in 22 (54%) tumors, thin as opposed to thick papillae predominated. Accordingly, UPSC may be broadly defined as a carcinoma that displays foci of well-differentiated papillae lined by cells that are markedly atypical cytologically. UPSC frequently contain areas of clear cells. Glands with papillary infoldings sometimes predominate in the invasive component. Because the behavior of endometrial neoplasms, in which at least 25% of the carcinoma exhibits a glandular or papillary architecture with serous differentiation, is similar, the term "uterine serous carcinoma" is an appropriate designation for these tumors, regardless of whether other patterns of differentiation are present or whether the tumor is associated with a polyp. PMID- 1599039 TI - Adrenal carcinosarcoma presenting in a woman with clinical signs of virilization. A case report with immunohistochemical and ultrastructural findings. AB - An adrenal carcinosarcoma is reported in a 29-year-old female presenting with clinical signs of virilization. This is the first reported case of a functioning adrenal carcinosarcoma in the English language literature. The tumor measured 12.5 cm in greatest dimension, weighed 610 g, and consisted of large areas of typical adrenal cortical carcinoma that was, however, interspersed with multiple foci of sarcoma. Rhabdomyosarcomatous elements were identified and confirmed both immunohistochemically and ultrastructurally. After radical resection, the patient received adjuvant mitotane therapy but developed rapid local and metastatic recurrence. Systemic chemotherapy was unsuccessful, and the patient died 8 months after surgery. PMID- 1599040 TI - The 1991 Fred W. Stewart Award. 14th recipient of the Fred W. Stewart Award: Javier Arias Stella, M.D. PMID- 1599041 TI - Fred W. Stewart: renewed thanks. PMID- 1599042 TI - False-negative temporal artery biopsy. PMID- 1599043 TI - Rosette formation in Plasmodium falciparum isolates and anti-rosette activity of sera from Gambians with cerebral or uncomplicated malaria. AB - The ability of Plasmodium falciparum-infected red blood cells (RBC) to form spontaneous erythrocyte rosettes was studied in 130 fresh isolates from Gambian children with cerebral or uncomplicated malaria from August to November 1990. All isolates (24 of 24) from patients with cerebral malaria formed rosettes, but only 61 of 106 isolates from children with uncomplicated malaria formed rosettes. The mean rate of rosette formation in isolates from children with cerebral malaria (28.3%) was significantly greater than that in isolates from children with uncomplicated malaria (8.5%). Giant rosettes were more frequently formed in isolates from patients with cerebral malaria than in those from patients with uncomplicated malaria. Sera of children with cerebral disease generally lacked anti-rosette activity, while many sera from children with uncomplicated malaria showed strong anti-rosette activity when tested against the patients' ow parasites. Some sera that were devoid of autologous rosette-disrupting activity were able to disrupt rosettes formed in other isolates, indicating the presence of different rosette formation mechanisms. Forty percent (6 of 15) of the sera from patients with cerebral malaria caused microagglutination of the patients' own uninfected and infected RBC, while only 10% (3 of 31) of sera from children with uncomplicated disease caused microagglutination. The ability of infected RBC to bind to melanoma cells grown in vitro did not differ between patients with cerebral or uncomplicated malaria. The results of this study, taken in conjunction with our previous findings, establish a strong association between rosette formation in P. falciparum-infected RBC and cerebral malaria. PMID- 1599044 TI - Ultrastructural analysis of fresh Plasmodium falciparum-infected erythrocytes and their cytoadherence to human leukocytes. AB - Sixty fresh Plasmodium falciparum isolates obtained from Gambian children with mild or cerebral malaria were investigated by transmission electron microscopy for the expression of knob-like protrusions (K+) on the surface of the infected erythrocytes. More than six-hundred infected erythrocytes were analyzed. Knob forming parasites were present in all 60 isolates. Although knobless parasites (K ) were found in 25 (42%) of the isolates, only 39 were K-, while 577 were K+. Nine of the 39 K- infected erythrocytes that were studied in greater detail appeared to be asexual parasites because they were either segmented or they lacked mitochondrial DNA-like filaments and cristae, which are abundant in immature gametocytes. No difference was observed in the relative frequency of K+K infected erythrocytes in isolates from patients with mild or cerebral malaria. Binding of both knobby and knobless infected erythrocytes to autologous leukocytes including monocytes, neutrophils, lymphocytes and plasma cells was found in some of the primary in vitro cultures. By using P. falciparum laboratory strains of known phenotypes and leukocytes from healthy blood bank donors, it was established that this novel adherence phenomenon was related to that of cytoadherence to certain melanoma or endothelial cells. Cytoadherent infected erythrocytes that bind to leukocytes enhance antibody-independent phagocytosis and induce cellular aggregation, while non-cytoadherent or rosetting infected erythrocytes do not.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599045 TI - Release of prostaglandin E2 by microfilariae of Wuchereria bancrofti and Brugia malayi. AB - To elucidate the local release of immunomodulatory prostaglandins by intravascular filarial parasites, the formation of prostaglandin E2 (PGE2) was examined in individual microfilariae of Wuchereria bancrofti and Brugia malayi. Following incubation of living microfilariae immobilized in an agar matrix, prostaglandins released by the parasites were fixed by carbodiimide and localized by indirect immunofluorescence. Prostaglandin E2 was specifically detected around the entire surface of microfilariae with anti-PGE2 antiserum, but not with control nonimmune or PGE2 affinity-immunoadsorbed antiserum. These results provide direct evidence that individual microfilariae of W. bancrofti as well as B. malayi release prostaglandins into their microenvironment. The release of PGE2 by these intravascular parasites may modulate host leukocyte responses, and thereby contribute to the immune defects observed in infected humans with peripheral microfilaremia. PMID- 1599046 TI - Genomic and biologic analyses of snowshoe hare virus field and laboratory strains. AB - Low-passage field strains of snowshoe hare (SSH) virus (Bunyaviridae), the prototype SSH virus (originally isolated in Montana), and La Crosse (LAC) virus were compared serologically by plaque-reduction neutralization (PRNT) and molecularly by oligonucleotide fingerprinting (ONF). The PRNT and ONF results confirmed the identity of the field strains, although some differences in the fingerprints were observed. We have examined the RNA genome variability in the two field and three laboratory strains of SSH virus, using direct sequence analysis of selected RNase T1 oligonucleotides. Few changes were observed among three Montana prototype-derived laboratory isolates, although they have different passage histories. In contrast, the field isolates differed greatly from the laboratory strains. In addition, we have located several of the larger T1 oligonucleotides within the known sequence of the small and large RNA genome segments. We then compared the viruses for their ability to replicate in and be transmitted by Aedes triseriatus mosquitoes. The oral infection rates for LAC, the field isolates, and the SSH prototype, as determined by immunofluorescent examination of midgut tissues, were 100%, 82%, and 47%, respectively. All viruses were also transmissible from mosquitoes to mice. PMID- 1599047 TI - Occurrence of severe leptospirosis in a breeding colony of squirrel monkeys. AB - Although experimental leptospirosis has been studied in various species of monkeys, the occurrence of acute leptospirosis in a population of nonhuman primates is uncommon. We report on a number of severe cases of icterohemorrhagic leptospirosis that appeared in the squirrel monkey (Saimiri sciureus) colony of 109 animals at the Institute Pasteur in French Guiana. Initially, 11 animals had acute illness, with jaundice and a hemorrhagic syndrome, leading to 10 deaths. Two Leptospira interrogans strains were isolated from blood cultures of sick monkeys, and one was isolated from the urine of a rat trapped in the breeding park. All three belonged to serovar copenhageni, and tests using monoclonal antibodies showed that these three strains were extremely similar. In the following weeks, five pregnant female monkeys had miscarriages; two of them had antibodies against the Icterohaemorrhagiae serogroup. An epidemiologic study conducted on the 93 remaining animals demonstrated a seropositivity rate of 26% (microagglutination test [MAT] titer greater than or equal to 100) primarily for the Icterohaemorrhagiae serogroup, but also for the Ballum, Grippotyphosa, Sejroe, and Panama serogroups. In addition, 12% showed lower MAT titers (50) for the same serogroups. Lastly, recently trapped feral squirrel monkeys were shown to have agglutinins against the Grippotyphosa and Sejroe serogroups. A vaccine, which was prepared from one of the strains isolated, was used in addition to antibiotic prophylaxis to control the enzootic disease. This confirms that the squirrel monkey is highly susceptible to icterohemorrhagic leptospirosis and is probably receptive to other serogroups, and that this animal may be useful in studying experimental leptospirosis and for testing new human vaccines. PMID- 1599048 TI - Spotted fever rickettsiae in ticks from the northern Sinai Governate, Egypt. AB - A field study was initiated in 1988 to investigate whether spotted fever group rickettsiae occur in geographic areas in Egypt that are adjacent to an area in the southern Israeli Negev that has a defined focus of spotted fever disease. Ticks were collected from dogs, sheep, and camels at four study sites in the northern Sinai. Tick hemolymph was processed for rickettsial detection by staining with fluorescein isothiocyanate-conjugated antibody to Rickettsia rickettsii. Of the 442 hemolymphs examined, 15 contained immunofluorescent rickettsiae. Eight hemolymph test-positive (HT+) ticks were Rhipicephalus sanguineus removed from dogs; the other HT+ ticks comprised three Hyalomma species, H. anatolicum, H. impeltatum, and H. dromedarii. Both HT+ and HT- ticks were tested for rickettsial DNA using the polymerase chain reaction (PCR). Eight of 10 HT+ field-collected ticks were PCR positive (PCR+). All laboratory colony R. rickettsii-infected ticks were PCR+. No HT- ticks from field or laboratory isolates were PCR+. PMID- 1599049 TI - The natural history of endemic trachoma: a longitudinal study. AB - A longitudinal study of trachoma was conducted among 100 members of nine families living in a hyperendemic area of Tanzania. Family members were examined for trachoma every three months for one year and conjunctival specimens were collected for antigen detection, which was performed either by direct fluorescent antibody cytologic analysis or enzyme immunoassay. The serovar specificity of tear antibodies was determined. Overall, young children tended to form a core of those with persistent, often severe, disease who consistently shed Chlamydia. These children are a potential source of infection in their family. Chlamydia could be identified early in the course of presumed recently acquired infections, but not later in resolving infections. This temporal change may account for the discrepancies between demonstrable organisms and clinical disease seen in cross sectional studies. Several children were identified who did not develop trachoma despite having Chlamydia identified in conjunctival scrapings. Their ability to resist infection may offer clues for vaccine development. The study of serovar specificity is consistent with the intrafamily transmission of trachoma, but was confounded by the large family size and the potential for separate transmission units to occur within large extended families. These observations give further understanding of the natural history and kinetics of the transmission of trachoma that should be of use in developing and evaluating intervention studies. PMID- 1599050 TI - Epidemic dermatitis due to contact with a moth in Cozumel, Mexico. AB - In early December 1989, an outbreak that was initially thought to be scabies was investigated among employees of tourist hotels in Cozumel, Mexico. Of 417 employees interviewed, only 19 (4.6%) met a case definition for scabies dermatitis, while 91 (21.8%) reported a nonspecific dermatitis of less than one week's duration. Persons with nonspecific dermatitis related the onset of their dermatitis to skin contact with a moth that had been present in large numbers in November. At the time of the initial investigation in December, there were no active cases of dermatitis and the moth was no longer present. During early January 1990, numerous cases of dermatitis again began to be reported. Using a case definition for nonspecific dermatitis, a survey of Cozumel's resident population showed an attack rate of 12.1%. A case-control study revealed the only significant risk factor to be skin contact with the suspect moth (P less than 0.01), which had returned in large numbers. Six health workers volunteered to have the moth rubbed on their skin; within 5 min, five of six developed an intense pruritus followed by an erythematous rash. The moth was classified as Hylesia alinda Druce. This species has nettling hairs on its abdomen that excrete a histamine-like substance. Although this moth is normally present in small numbers in Cozumel, the passage of hurricane Gilbert killed most of its natural predators (wasps and bees), allowing its population to overgrow. No control measures were undertaken because the moth's natural predators returned that spring and dramatically reduced the moth population. No further outbreaks of dermatitis occurred. PMID- 1599051 TI - Child growth and schistosomiasis japonica in northeastern Leyte, the Philippines: cross-sectional results. AB - The association between schistosomiasis japonica and child growth was studied cross-sectionally in 1,561 males and females aged 4-19.9 years residing in an endemic region of northeastern Leyte, The Philippines. Stature, weight, upper arm muscle area, and sum of triceps and subscapular skinfold thicknesses were measured and related to presence of Schistosoma japonicum eggs in Kato stool smears and to the intensity of infection assessed by quantitative egg count. The presence of hookworm, ascaris, and trichuris eggs was also measured. Multivariable models were used to control for the effects of age, age2, and polyparasitism on growth. The prevalence of schistosomiasis was 31% in males and 22% in females, with the maximum prevalence in adolescence. In 8-19-year-old subjects, the intensity of schistosomiasis japonica was significantly related in males to reduced arm muscle area and sum of skinfolds (both P less than 0.01) and in females to reduced stature, weight, arm muscle area, and sum of skinfolds (all P less than 0.01). The greatest age-specific differences were during adolescence in both males and females. The growth retarding effects of intensity of schistosomiasis japonica were independent of the influence of other parasites, notably hookworm. Due to the magnitude of the schistosomiasis-associated growth differences in adolescence, adult body size, function and productivity may be affected. PMID- 1599052 TI - Plasma pharmacokinetics and therapeutic efficacy of praziquantel and 4 hydroxypraziquantel in Schistosoma japonicum-infected rabbits after oral, rectal, and intramuscular administration. AB - The relationship between plasma level and therapeutic efficacy of praziquantel (PZQ) and its major human oxidative metabolite, 4-hydroxypraziquantel (4-OHPZQ), has been investigated in Schistosoma japonicum-infected rabbits using three different routes of PZQ administration. After intramuscular administration (20 mg/kg), the maximum level of PZQ in rabbit cardiac plasma was 1.6 +/- 1.0 micrograms/ml (mean +/- SD) 30 min after administration. After oral or rectal administration (40 mg/kg), maximum plasma levels were 0.1 +/- 0.2 microgram/ml (oral) and 0.5 +/- 0.4 micrograms/ml (rectal). The corresponding maximum 4-OHPZQ concentrations in cardiac plasma were 4.6 +/- 1.8 micrograms/ml (intramuscular), 1.7 +/- 0.5 micrograms/ml (oral), and 4.1 +/- 1.6 micrograms/ml (rectal) 2 hr after administration of PZQ. After administration of similar doses, maximum levels of PZQ in plasma from the femoral vein were 29.3 +/- 27.5 micrograms/ml (intramuscular), 0.6 +/- 1.0 microgram/ml (oral), and 0.7 +/- 0.6 microgram/ml (rectal). However, 60 min after intramuscular administration, the maximum PZQ concentration in portal venous blood was only 1.0 +/- 0.6 microgram/ml, which is substantially less than corresponding maximum portal vein levels after oral (6.8 +/- 6.5 micrograms/ml) or rectal (3.7 +/- 4.6 micrograms/ml) administration. Therapeutically, in spite of the 4-6-fold lower levels of PZQ in portal venous plasma after intramuscular administration, adult worm reduction rates in infected rabbits using the above doses were 92.2% (intramuscular), 90.1% (rectal), and 72.5% (oral), respectively, four weeks after treatment. Thus, no direct correlation between levels of PZQ in peripheral or portal venous blood and therapeutic efficacy was observed in rabbits infected with S. japonicum. PMID- 1599053 TI - Effect of different fractions of heparin on Plasmodium falciparum merozoite invasion of red blood cells in vitro. AB - Heparin and various heparin fractions were separated according to differences in molecular weight or affinity for antithrombin III and used for the inhibition of Plasmodium falciparum merozoite invasion of red blood cells in vitro. No variation in sensitivity to heparin was found among the four strains of P. falciparum tested; all required approximately 5 micrograms/ml (0.5 U/ml) of heparin for 50% inhibition of invasion. The most efficient fraction of heparin was the one with low affinity for antithrombin III. Its 50% inhibition concentration was 1 microgram/ml, indicating that it was more efficient than unfractionated heparin and other heparin fractions. The effect of heparin was reversible, since washing of heparin-treated cultures containing mainly schizonts showed no inhibition of merozoite invasion. The results suggest that a heparin fraction with no anticoagulant effect might be useful in the treatment of patients with falciparum malaria. PMID- 1599054 TI - Disruption of Plasmodium falciparum erythrocyte rosettes by standard heparin and heparin devoid of anticoagulant activity. AB - We have studied the ability of heparin to disrupt spontaneous rosettes formed between Plasmodium falciparum-infected and uninfected red blood cells, which has been proposed to have importance in the pathogenesis of cerebral malaria. Substantial variation in this activity was found among six laboratory stains of P. falciparum. Rosettes formed by three of these strains were highly sensitive to heparin (50% disruption at 0.5-25 micrograms/ml; 1 microgram/ml corresponds to 0.15 IU/ml). The rosettes formed by two other strains showed a much lower sensitivity (50% disruption at 700-2,500 micrograms/ml), while the rosettes formed by another strain were almost completely resistant to heparin (20% disruption at 6,500 micrograms/ml). The ability of heparin (65 or 650 micrograms/ml) to disrupt rosettes formed by 54 fresh Gambian isolates of P. falciparum also varied. Rosettes of 27 (50%) of the 54 isolates were disrupted to a significant degree (greater than or equal to 15%), while rosettes of the other 27 isolates remained unaffected at the concentrations tested. Heparin was fractionated by molecular weight and/or affinity for antithrombin III. We found that its property of rosette disruption was associated, to some extent, with size (high molecular weight) but not with its anticoagulant potential (affinity for antithrombin III). A heparin fraction with low affinity for antithrombin III and one with combined high molecular weight and low affinity for antithrombin III were as effective at disrupting rosettes as standard heparin, while a chemically modified (N-acetylated) high molecular weight-heparin fraction, similarly devoid of anticoagulant activity, lacked strong anti-rosette potential.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599055 TI - Use of the Falcon assay screening test--enzyme-linked immunosorbent assay (FAST ELISA) and the enzyme-linked immunoelectrotransfer blot (EITB) to determine the prevalence of human fascioliasis in the Bolivian Altiplano. AB - A collaborative study between the University of Puerto Rico School of Medicine, the Centers for Disease Control, the Bolivian Ministry of Health, and private voluntary organizations (Foster Parents Plan International and Danchurchaid) working in Bolivia has identified a region in the northwestern Altiplano of Bolivia near Lake Titicaca as harboring the highest prevalence of human fascioliasis in the world reported to date. Two serologic techniques (the Falcon assay screening test-enzyme-linked immunosorbent assay [FAST-ELISA] and the enzyme-linked immunoelectrotransfer blot [EITB]) were used in the determination of its prevalence. One hundred serum samples and 73 stool samples were obtained from Aymara Indians from Corapata, Bolivia. Antibody absorbance levels to Fasciola hepatica excretion-secretion antigens were compared with EITB banding patterns using the same antigen preparation. A positive FAST-ELISA result was defined as an absorbance value greater than the mean plus three standard deviations of two sets of normal negative controls (Puerto Rican and Bolivian). Using this criterion, 53 of 100 sera tested were found positive by this technique. Within this group, 19 (95%) of 20 individuals who were parasite positive were also positive by FAST-ELISA. An additional 24 individuals who were negative for F. hepatica eggs and 10 individuals for whom no specimens were received were also positive by FAST-ELISA. Among the 53 individuals negative for F. hepatica eggs, 29 were also negative by FAST-ELISA. The EITB analysis of the sera from confirmed infected individuals revealed at least three F. hepatica (Fh) bands with molecular weights of 12, 17, and 63 kD, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599057 TI - An improved polymerase chain reaction assay to detect Trypanosoma cruzi in blood. AB - Amplification by the polymerase chain reaction of Trypanosoma cruzi satellite DNA was used to enhance sensitivity in the detection of the parasite in blood, with the ultimate goal of improving diagnosis of the chronic phase of Chagas' disease. Two contiguous oligonucleotides were synthesized corresponding to the most conserved region of the 195-basepair repeated sequence and used as primers for the amplification reaction. Nineteen femtograms of parasite DNA that was amplified in the presence of 15 micrograms of human or mouse DNA produced a visible band upon electrophoresis in agarose gels and staining with ethidium bromide. In reconstitution experiments, one parasite in 10 ml of blood could be unambiguously determined when the DNA was isolated from nuclei after the blood was treated with NP40 and centrifuged. Polymerase chain reaction assays were carried out to detect T. cruzi in chronically infected mice. Most mice were parasite-positive when organs or tissues were tested, but all were negative when total blood was tested. PMID- 1599056 TI - Immunodiagnosis of human cysticercosis (Taenia solium): a field comparison of an antibody-enzyme-linked immunosorbent assay (ELISA), an antigen-ELISA, and an enzyme-linked immunoelectrotransfer blot (EITB) assay in Peru. The Cysticercosis Working Group in Peru (CWG). AB - We compared results of an enzyme-linked immunosorbent assay (ELISA) and an enzyme linked immunoelectrotransfer blot (EITB) assay for the diagnosis of cysticercosis in sera and cerebrospinal fluid (CSF). Sera from 34 patients with confirmed cysticercosis were tested by both ELISA and EITB assays. Cerebrospinal fluid from some of these patients was also tested by ELISA for the presence of antibody (AB ELISA) (n = 21) and antigen (AG-ELISA) (n = 15). Specificity in sera was examined by testing 51 serum samples from Bangladesh, where cysticercosis is not endemic. Cross-reactivity was evaluated in sera from patients with Echinococcus granulosus (hydatid) and Hymenolepis nana infections. Sensitivity in detecting cysticercosis in sera was 94% by EITB and 65% by AB-ELISA (P less than 0.01). Sensitivities in the CSF tested by EITB, AB-ELISA, and AG-ELISA were 86%, 62%, and 67%, respectively. The specificity of the EITB was 100%, while that of AB-ELISA was 63% (P less than 0.01). Cross-reactions occurred in the AB-ELISA with 11% and 20% of sera from hydatid and H. nana patients, respectively. Our results demonstrate that the EITB is the best assay available for the diagnosis of cysticercosis in both sera and CSF. PMID- 1599058 TI - Upper oesophageal sphincter pressure and the intravenous induction of anaesthesia. AB - The upper oesophageal sphincter can prevent regurgitation of oesophageal contents into the pharynx following gastrooesophageal reflux in the awake patient. Upper oesophageal sphincter pressure was recorded with a Dent sleeve after hypnosis with midazolam (n = 7) and also during the rapid intravenous induction of anaesthesia with thiopentone (n = 16) or ketamine (n = 7). Thiopentone decreased mean (SD) sphincter pressure from an awake value of 43 (19) to 9 (7) mmHg (p less than 0.001) and midazolam from 38 (25) to 7 (3) mmHg (p less than 0.02). Mean (SD) sphincter pressures before and after ketamine were not significantly different at 29 (15) and 32 (21) mmHg respectively. After suxamethonium mean (SD) sphincter pressure in all patients (n = 30) was 7 (4) mmHg. Laryngoscopy (n = 30) caused a small increase in mean (SD) sphincter pressure to 13 (10) mmHg (p less than 0.001). Thiopentone caused a rapid fall in upper oesophageal sphincter pressure which usually started before loss of consciousness. These findings have implications for the timing of cricoid pressure application. PMID- 1599060 TI - Propofol and hypothermic cardiopulmonary bypass. Vasodilation and enhanced metabolic protection? AB - The effects of propofol during low flow (1.6 l.min-1.m-2) hypothermic (27-29 degrees C) cardiopulmonary bypass on systemic haemodynamic and metabolic variables were studied in 20 patients in a parallel group comparison. Patients in the control group underwent two consecutive control periods, whereas those in the propofol group underwent a control period followed by a 'propofol' period during which they received an intravenous bolus of propofol 5 mg.kg-1 followed by an infusion at a rate of 20 mg.kg-1.h-1. Haemodynamic and metabolic variables were measured at the end of each period. The propofol group showed a significant reduction in both systemic vascular resistance (p less than 0.001) and systemic oxygen uptake (p less than 0.05). There was a small but significant fall in lactate in the control group (p less than 0.02); however, there was no significant change in the propofol group. These findings could indicate impaired tissue perfusion, although they more likely indicate systemic metabolic depression with washout of lactate from previously hypoperfused tissues. PMID- 1599059 TI - Intra-operative patient-controlled sedation. Comparison of patient-controlled propofol with patient-controlled midazolam. AB - Propofol and midazolam were compared for intra-operative patient-controlled sedation in 40 ASA 1 day patients undergoing surgical extraction of third molar teeth under local anaesthesia. All patients initially received 0.7 micrograms.kg 1 fentanyl. Patients in the propofol group self-administered 20 mg (2 ml over 6 s) bolus doses of propofol; successful demands averaged 8.0 (SD 4.4) and unsuccessful demands (during the 1 min lockout period) 2.8 (SD 4.1). The midazolam group self-administered 0.5 mg (2 ml over 6 s) bolus doses and averaged 14.0 (SD 6.3) and 17.6 (SD 19.8) successful and unsuccessful demands respectively. Postoperative memory, measured with delayed free recall, and postoperative mental performance, measured with the frequency accrual speed test index, were both significantly less impaired in the propofol group. Although there was no significant difference in patient satisfaction, measured postoperatively, propofol was judged the more suitable agent for patient controlled sedation, because of its more rapid response to fluctuating intra operative requirements, superior recovery characteristics and beneficial effect on mood. PMID- 1599061 TI - Thoracic epidural infusion for postoperative pain relief following abdominal aortic surgery: bupivacaine, fentanyl or a mixture of both? AB - Thirty patients who had undergone elective abdominal aortic surgery were studied in a prospective, randomised double-blind comparison of thoracic epidural 0.2% bupivacaine alone, thoracic epidural fentanyl alone and thoracic epidural 0.2% bupivacaine combined with fentanyl. Pain relief, pulmonary function, cardiovascular stability and side effects were assessed. Pain relief was excellent in the combined bupivacaine-fentanyl series, being significantly better than the other groups (p less than 0.05) during the entire study period and was not accompanied by hypotension. Forced expiratory parameters were reduced in all groups throughout the study to 50-60% of the pre-operative values, but there were no significant differences between groups. The incidence of side effects attributable to either epidural bupivacaine or fentanyl was low. This study supports the increasing use of epidural infusion analgesia for postoperative pain management after abdominal surgery. PMID- 1599062 TI - Fentanyl-prilocaine mixture for intravenous regional anaesthesia in patients undergoing surgery. AB - The effect of the addition of 0.1 mg or 0.2 mg fentanyl to 40 ml 0.5% prilocaine in intravenous regional anaesthesia of the arm was investigated in 37 patients in a randomised, double-blind study. The characteristics of the sensory and motor block were studied. There was no difference in the speed of onset of analgesia in the groups (mean latency approximately 4 min in each group). However, significantly more patients in the fentanyl 0.2 mg group (7/12) had complete anaesthesia at 15 min than in the fentanyl 0.1 mg group (1/13) and the control group (2/12) (p less than 0.05). There were no differences in the incidence of tourniquet pain immediately before cuff deflation (tourniquet time 45-87 min). After cuff deflation, in those patients who complained of wound pain within 30 min, on average the pain appeared later in the fentanyl 0.2 mg group (six patients, mean 14.3 min) than in the control group (eight patients, mean 9.4 min) (ns). In the fentanyl groups, the incidence of central nervous system side effects was greater than in the control group (fentanyl 0.1 mg 7/13 patients, fentanyl 0.2 mg 6/12 patients, control 1/12 patients) (p less than 0.05). The plasma concentrations of prilocaine after cuff deflation were higher, in a dose dependent fashion, in the fentanyl groups than in the control group, but the concentrations of prilocaine and fentanyl did not correlate with the symptoms. Postoperative nausea occurred only in the patients who had received fentanyl. PMID- 1599063 TI - Transdermal hyoscine with patient-controlled analgesia. AB - Transdermal hyoscine (Scopoderm TTS CIBA) was compared with placebo in 67 patients receiving postoperative analgesia via a patient-controlled analgesia system. All patients underwent an abdominal hysterectomy and had a standard anaesthetic. They were followed up in recovery and daily for 3 days postoperatively. Fewer patients in the hyoscine group suffered emetic sequelae in recovery and on the third postoperative day (p less than 0.05). The hyoscine group received half the number of supplementary antiemetic doses compared to placebo. However, despite transdermal hyoscine there was still a high (78%) incidence of nausea and vomiting. The only significant (p less than 0.05) increase in side effects attributable to hyoscine was a higher reported incidence of visual disturbance on the second day. PMID- 1599065 TI - Anaesthesia for cardiac surgery in children with nemaline myopathy. AB - Nemaline myopathy is a rare congenital myopathy associated with skeletal deformities and respiratory complications. Three children with nemaline myopathy who underwent cardiac surgery are described where the heart rate decreased during induction of anaesthesia and body temperature increased during or after the surgery. The anaesthetic implications in the management of patients with nemaline myopathy are discussed. PMID- 1599064 TI - Patient-controlled analgesia. A serious incident. AB - A patient received a massive overdose of papaveretum intravenously (estimated to be 180 mg) when the glass syringe of a patient-controlled analgesia machine disengaged from the drive mechanism. She was successfully resuscitated. The pump, on loan from the supplier, had passed a brief evaluation by the infusion pump test house designated by the Medical Devices Directorate of the Department of Health; it has since been withdrawn. It is recommended that patient-controlled analgesia equipment should be placed at or below patient heart level. The Department of Health is called on to institute a full, independent evaluation scheme for patient-controlled analgesia equipment. PMID- 1599066 TI - Pulmonary vasoconstriction following intravenous nimodipine. AB - A case is reported in which intravenous nimodipine therapy was associated with severe acute pulmonary hypertension in a patient with a subarachnoid haemorrhage. The patient had previously received enteral nimodipine without problems. PMID- 1599067 TI - Pulmonary collapse during anaesthesia in children with respiratory tract symptoms. AB - A frequent dilemma facing the anaesthetist is the child with respiratory tract symptoms. The risks of anaesthesia and surgery in these patients have not been clearly established. We present three cases which illustrate a potentially serious complication which may arise. Our patients each had symptoms of cough, but were systemically healthy. Two of the children had absent clinical signs, whilst the third had a normal chest X ray. However, during surgery and anaesthesia each child developed significant pulmonary collapse, associated with desaturation on oximetry. PMID- 1599068 TI - A comparison of the filtration properties of heat and moisture exchangers. AB - Heat and Moisture Exchangers are used increasingly as filters to prevent the contamination of breathing apparatus and to limit cross-infection. A series of laboratory tests has been developed to evaluate the microbial filtration and air flow resistance properties of these devices. The tests were designed to simulate the clinical situation and therefore evaluated devices in both dry and wet conditions. The devices tested (Engstrom Edith, Pall BB50T, Dar Hygrobac, Intersurgical Filtatherm and Intersurgical Filtaguard) were each representative of a particular type of construction. The simple hygroscopic device (Engstrom Edith) showed poor airborne and liquid-borne filtration efficiency, but its resistance to air flow remained low in all conditions. The composite devices (Dar Hygrobac, Intersurgical Filtatherm and Intersurgical Filtaguard), which all possessed relatively large pores, performed well in terms of dry airborne filtration efficiency, but showed substantial increases in air flow resistance and poor filtration efficiency in the presence of liquid. The pleated membrane filter (Pall BB50T), which possessed small pores, showed good airborne filtration efficiency and prevented the passage of liquid. The latter property enabled this device to prevent the passage of liquid-borne contamination and to maintain a low resistance to air flow in wet conditions. It would appear that in terms of contamination control and air flow resistance the pleated membrane filter provides a wider margin of safety than either the hygroscopic or composite devices. PMID- 1599069 TI - High frequency jet ventilation for microlaryngeal laser surgery. An improved technique. AB - The use of a triple lumen central venous catheter, which can be shielded from laser irradiation by metal tape, as a conduit for high frequency jet ventilation in six children, is described. The problems of anaesthesia for laryngeal laser surgery and the advantages of the technique described in this paper are discussed. PMID- 1599070 TI - Clinical measurement and clinical practice. PMID- 1599071 TI - The human wedge. A manoeuvre to relieve aortocaval compression during resuscitation in late pregnancy. AB - The important part of resuscitation in late pregnancy is the relief of aortocaval compression. A manoeuvre to relieve aortocaval compression (the human wedge) is described and evaluated. Eighteen qualified midwives performed basic life support in the supine and wedged position employing the human wedge. Performance was assessed using the Laerdal Resusci Anne Skillmeter. There was no difference (p = 0.4761) in performance of mouth-to-mouth expired air ventilation between the two positions. External cardiac compressions were performed significantly better (p = 0.0005) in the wedged position than in the supine position. The human wedge may provide an alternative to other methods of relieving aortocaval compression. PMID- 1599072 TI - Epidural pethidine and bupivacaine in labour. AB - A double-blind randomised study was performed to assess the value of the addition of pethidine 50 mg to the initial dose of bupivacaine given for epidural analgesia in labour. Forty-nine patients received either 1 ml of saline (n = 24), or 50 mg of pethidine (n = 25), added to 9 ml of 0.25% bupivacaine as an initial injection for intrapartum epidural analgesia. There was a significant increase in the mean duration of analgesia in the pethidine group. However, pethidine did not increase the speed of onset of analgesia, or improve the quality of analgesia. PMID- 1599073 TI - The effect of music on ketamine induced emergence phenomena. AB - The purpose of this investigation was to assess the influence of music on emergence phenomena after ketamine anaesthesia. Fifty ASA 1 patients undergoing minor gynaecological procedures were randomly divided into two equal groups. Patients in the treated group were played music of their choice through headphones from 5 min before induction of anaesthesia to 15 min postoperatively. Although the incidence of emergence phenomena was similar in both groups the effects tended to be more pleasant and acceptable in those to whom music was played. The majority of patients in the study group (80%) expressed their willingness to have a similar anaesthetic in the future compared to 52% in the control group (p less than 0.05). PMID- 1599074 TI - Predicting difficult intubation. PMID- 1599075 TI - Opisthotonus and propofol. PMID- 1599076 TI - Abnormal movements following recovery from propofol, alfentanil and nitrous oxide anaesthesia. PMID- 1599077 TI - Use of propofol to terminate generalised myoclonus. PMID- 1599078 TI - Another modification of the oesophageal detector device. PMID- 1599079 TI - Potential occlusion of the BOC Mk4 circle absorber. PMID- 1599080 TI - Post-thyroidectomy vocal cord examination by fibreoscopy aided by the laryngeal mask airway. PMID- 1599081 TI - The laryngeal mask airway and intra-ocular surgery. PMID- 1599082 TI - Laryngeal mask airway for radiotherapy in the prone position. PMID- 1599083 TI - Epidural needle rotation and inadvertant dural puncture with catheter. PMID- 1599084 TI - Disposable EMLA patches. PMID- 1599085 TI - Postpartum headache and cerebral tumour. PMID- 1599086 TI - Muscle damage with diclofenac injections. PMID- 1599088 TI - Recent developments in pulse oximetry. PMID- 1599087 TI - Halothane, enflurane, and isoflurane attenuate both receptor- and non-receptor mediated EDRF production in rat thoracic aorta. AB - EDRF (endothelium-derived relaxing factor) is a cellular and intercellular messenger that activates soluble guanylate cyclase. In blood vessels it is released from the endothelium and causes relaxation of vascular smooth muscle. Halothane previously has been shown to attenuate EDRF-induced vasodilation elicited by the receptor-mediated vasodilators acetylcholine and bradykinin and to alter muscarinic receptor activity. We examined and compared the effects of the inhaled anesthetics halothane, enflurane, and isoflurane on endothelium dependent vasodilation and tested the hypothesis that these agents inhibit EDRF mediated vasodilation solely through inhibition of endothelial cell receptor mediated EDRF release. Isolated rat thoracic aortic rings were mounted for isometric tension recording and preconstricted with phenylephrine. Cumulative dose-response curves were obtained to methacholine, a receptor-mediated endothelium-dependent dilator; to A23187, a nonreceptor-mediated endothelium dependent dilator; and to sodium nitroprusside, a direct-acting endothelium independent dilator before, during, and after inhalational anesthetic exposure. Both receptor-mediated and non-receptor-mediated endothelium-dependent relaxation by methacholine and A23187, respectively, were significantly (P less than 0.01 to P less than 0.05) and reversibly attenuated by halothane, enflurane, and isoflurane at 2 MAC and by isoflurane at 1 MAC. Endothelium-independent relaxation by sodium nitroprusside, an agent that acts directly on the vascular smooth muscle cell to activate guanylate cyclase, was unaffected by any of the anesthetics at any concentration tested. Indomethacin had no significant effect on the inhibition of endothelium-dependent vasodilation by these inhalational anesthetics. We conclude that halothane, enflurane, and isoflurane inhibit endothelium-dependent vasodilation; that isoflurane is more potent than halothane and enflurane in this regard.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599089 TI - Prospects for the diagnosis of malignant hyperthermia susceptibility using molecular genetic approaches. AB - MHS is a heterogeneous pharmacogenetic disorder in the human that is likely to be caused by one of a variety of genetic defects, in one of a number of genes. Direct molecular methods will provide a rapid, efficient, non-invasive, and low cost screening test once the causative genetic mutations have been identified. However, until this objective is met, indirect molecular genetic methods can be used to demonstrate the inheritance of an abnormal gene in certain family members at risk. This requires localizing the gene that produces the abnormal phenotype to a subchromosomal segment by linkage analysis and showing the coinheritance of MHS and DNA markers in a number of family members. Indirect molecular genetic methods are likely to be particularly useful in the diagnostic evaluation of children too small to be biopsied in families where others have been biopsied or their phenotypes are known. It appears likely that molecular genetic methods will not eliminate the usefulness of the muscle biopsy and caffeine-halothane contracture test in the near future. Rather, these diagnostic tests will complement one another and significantly improve our understanding of the complexity of this disorder. PMID- 1599090 TI - Neuromuscular effects of subcutaneous administration of pancuronium. PMID- 1599092 TI - Inverted left atrial appendage appearing as a left atrial mass with transesophageal echocardiography during cardiac surgery. PMID- 1599091 TI - Flumazenil counteracts intrathecal baclofen-induced central nervous system depression in tetanus. PMID- 1599093 TI - Recurrence of thoracic and labial herpes simplex virus infection in a patient receiving epidural fentanyl. PMID- 1599094 TI - A valuable alternative for laryngeal visualization of the difficult airway. PMID- 1599095 TI - Advice to the patient with a difficult airway. PMID- 1599096 TI - Tracheal extubation. PMID- 1599098 TI - J-wire facilitates translaryngeal guided intubation. PMID- 1599097 TI - The Belscope for management of the difficult airway. PMID- 1599099 TI - Another problem in differentiating between carotid artery and jugular vein cannulation. PMID- 1599100 TI - Use of the color test for safer internal jugular vein cannulation. PMID- 1599101 TI - "The educated hand". PMID- 1599103 TI - Torsion of a double-lumen tube in the left bronchus. PMID- 1599102 TI - Skin hyperpigmentation following removal of electrocardiogram pads. PMID- 1599104 TI - Pneumothorax reexacerbated by a self-inflating bag-valve device. PMID- 1599105 TI - The ethics of using animal models to study treatment of phantom pain. PMID- 1599106 TI - Neonatal postoperative apnea--unexplained? PMID- 1599107 TI - Concerns regarding barotrauma during jet ventilation. PMID- 1599108 TI - Monitoring of the electroencephalogram during cardiopulmonary bypass. Know when to say when. PMID- 1599109 TI - Electroencephalography during surgery with cardiopulmonary bypass and hypothermia. AB - After more than 30 yr of use, electroencephalographic (EEG) monitoring during cardiopulmonary bypass has not gained wide clinical acceptance. To assess its utility to predict central nervous system injury, two-channel recordings were made from 78 patients undergoing cardiopulmonary bypass and anesthetized with fentanyl/diazepam/enflurane. The perfusion regimen included the use of high pump flow, a bubble oxygenator, and no arterial tubing filter. Target values were 28 32 degrees C for the minimum rectal temperature, 60-80 mmHg for mean arterial pressure, and 20-25% for hematocrit. Eight descriptors of the Fourier power spectra of the EEG were calculated off-line, and outcome comparisons were made with the results from neuropsychological tests. Among 58 patients yielding complete data of acceptable quality, a statistically significant reduction in total power was observed from prebypass to postbypass, accompanied by an increase in the fractional power in the theta and beta frequency bands and in the spectral edge frequency. The shifts in total and theta power were weakly associated with short-term but not with long-term changes in neuropsychological scores. Nearly 40% of the patients' EEGs were corrupted with electrical noise at some time during bypass. In 15 patients selected for having high-quality recordings and no neuropsychological deficit, an extensive statistical analysis failed to reveal any consistent variation in the EEG descriptors with hypothermia. Under the conditions studied, it appears that for other than gross signal dropout, the strong background variability in the EEG makes it have little value for detecting harbingers of brain injury. PMID- 1599110 TI - Ventilatory effects of clonidine alone and in the presence of alfentanil, in human volunteers. AB - Clonidine, an alpha 2-adrenergic agonist, can potentiate opioid-induced analgesia. In a double-blind placebo-controlled study in human volunteers, we sought to determine whether clonidine also potentiates opioid-induced respiratory depression. Hypercapnic ventilatory responses (minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure) were measured in five healthy male volunteers on two separate occasions (with or without clonidine, approximately 3.5 micrograms.kg-1 orally) under the following conditions: baseline, 2 h after clonidine/placebo (alfentanil concentration of 0), and during computer-controlled alfentanil infusions to approximate plasma concentrations of 5, 10, 20, 40, and 80 ng.ml-1. Plasma alfentanil concentrations were measured before and after each rebreathing test, and clonidine concentrations were measured after each rebreathing test. The end-tidal CO2 (PET(CO2)) was measured continuously. Data were analyzed by repeated-measures analysis of variance. The PET(CO2) and measured concentrations of alfentanil were included as covariates, and a compound symmetry error analysis was assumed. Statistical significance was achieved when P less than 0.05. For minute ventilation, mean inspiratory flow rate, and mouth occlusion pressure there was a statistically significant relationship to the covariates of PET(CO2) and plasma alfentanil concentration. Clonidine, when compared to placebo, caused a small but significant depression of mean inspiratory flow rate. There was similarly a small, but statistically insignificant, depression of minute ventilation by clonidine. The mouth occlusion pressure was not affected by clonidine treatment. Clonidine treatment did not potentiate alfentanil-induced respiratory depression. Although the combination of an opioid and an alpha 2-adrenergic agonist may act synergistically for the analgesic response, there is no synergistic effect by this drug combination on respiratory depression. PMID- 1599111 TI - Incidence and risk factors for side effects of spinal anesthesia. AB - We prospectively studied 952 patients to identify the incidence of hypotension (systolic blood pressure less than 90 mmHg), bradycardia (heart rate less than 50 beats/min), nausea, vomiting, and dysrhythmia during spinal anesthesia. Historical, clinical, and physiologic data were correlated with the incidence of these side effects by univariate and multivariate analysis. Hypotension developed in 314 patients (33%), bradycardia in 125 (13%), nausea in 175 (18%), vomiting in 65 (7%), and dysrhythmia in 20 (2%). Variables conferring increased odds of developing hypotension include peak block height greater than or equal to T5 (odds ratio 3.8, P less than 0.001), age greater than or equal to 40 yr (2.5, P less than 0.001), baseline systolic blood pressure less than 120 mmHg (2.4, P less than 0.001), combination of spinal and general anesthesia (1.9, P = 0.01), spinal puncture at or above the L2-L3 interspace (1.8, P less than 0.001), and addition of phenylephrine to the local anesthetic (1.6, P = 0.02). Variables conferring increased odds of developing bradycardia include a baseline heart rate less than 60 beats/min (odds ratio 4.9, P less than 0.001), ASA physical status classification of 1 versus 3 or 4 (3.5, P less than 0.001), current therapy with beta-adrenergic blocking drugs (2.9, P less than 0.001), and peak block height greater than or equal to T5 (1.7, P = 0.02). Variables conferring increased odds of developing nausea or vomiting include addition of phenylephrine or epinephrine to the local anesthetic (3.0-6.3, P less than or equal to 0.003), peak block height greater than or equal to T5 (odds ratio 3.9, P less than 0.001), use of procaine (2.6-4.4, P less than or equal to 0.003), baseline heart rate greater than or equal to 60 beats/min (2.3, P = 0.03), history of carsickness (2.0, P = 0.01), and development of hypotension during spinal anesthesia (1.7, P = 0.009). Our results indicate that the incidence of side effects during spinal anesthesia may be reduced by 1) minimizing peak block height; 2) using plain solutions of local anesthetics; 3) performing the spinal puncture at or below the L3-L4 interspace; and 4) avoiding the use of procaine in the subarachnoid space. PMID- 1599112 TI - Methohexital dissolved in lipid emulsion for intravenous induction of anesthesia in infants and children. AB - The induction dose of thiopental and propofol has been shown previously to vary during childhood. The methohexital dose needed for satisfactory induction of anesthesia in 50% of patients (ED50) was determined in 75 infants and children, 1 month to 16 yr of age. An intravenous bolus of methohexital, dissolved in a lipid emulsion to decrease pain on injection, was given over 10 s. After 30 s the anesthesia mask was applied. The patient was considered to be asleep if there were no gross movements when the head was placed in the sniffing position and the anesthesia mask applied, and no response to verbal command (tested in children more than 4 yr of age) during the next 30 s while the patient breathed O2. ED50 (+/- SE) was 2.6 +/- 0.2 mg/kg in infants 1-6 months of age, 1.9 +/- 0.1 mg/kg in infants 7-11 months of age, 1.4 +/- 0.1 mg/kg in children 1-3 yr of age, 1.1 +/- 0.1 mg/kg in children 4-7 yr of age, and 1.3 +/- 0.1 mg/kg in children 8-16 yr of age. ED50 in each of the two groups of infants was significantly greater than ED50 in each of the three other groups (P less than 0.05). Pain or discomfort on injection was observed in 1 infant and 3 children (5%). Eight patients (11%) had apnea longer than 15 s, and excitatory phenomena occurred in 9 (12%). It is concluded that the dose of methohexital needed for induction of anesthesia varies with age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599113 TI - Dissolving methohexital in a lipid emulsion reduces pain associated with intravenous injection. AB - Pain often accompanies intravenous injection of 1% methohexital. The aim of the present study was to test whether pain on injection could be reduced by dissolving methohexital in a lipid emulsion (study A) and whether this would affect anesthetic potency (study B). In study A, 24 healthy volunteers, 36 +/- 1 yr (mean +/- SE), were given 1 ml 1% methohexital in saline, 1 ml 1% methohexital in lipid emulsion, and 5 ml 0.1% methohexital in saline in random order. The injections were given in a small vein in the forearm at 5-min intervals. One minute after each injection, the subject was asked to assess the injection pain on a visual analog scale (0-100 mm). The pain score (median [range]) was 44.5 (0 77) after 1% methohexital in saline, 0.5 (0-26) after 1% methohexital in a lipid emulsion, and 1.0 (0-26) after 0.1% methohexital in saline. The pain score for 1% methohexital in saline was significantly greater than those for the other two solutions (P less than 0.001 for each comparison). In study B, 42 patients, 41 +/ 3 yr, were given 1% methohexital in lipid emulsion (n = 22) or 1% methohexital in saline (n = 20). A bolus of either solution was administered over 10 s, and the patient was considered asleep if there was no gross movement or response to verbal command 40-70 s after injection.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599114 TI - Thoracic epidural anesthesia via the caudal approach in children. AB - We investigated the feasibility of performing thoracic epidural anesthesia via the caudal approach in 20 children (age 62 +/- 38 months and weight 18.5 +/- 7.3 kg; mean +/- standard deviation). Based on external landmarks, a predetermined length of 24-G epidural catheter (Concord Portex 20/24 microcatheter system) with stylet was passed into the epidural space through a 20-G intravenous catheter inserted through the sacrococcygeal ligament, and a radiograph of the abdomen and chest was obtained. The radiographically determined catheter tip position was within two vertebrae of the target position in 17 of 20 subjects. In one subject, it was impossible to advance the catheter more than 10 cm. The other two malpositioned catheters were successfully reinserted. Intraoperative caudal anesthesia and postoperative pain relief were satisfactory in all 20 subjects. We have found it possible to use the caudal approach to thoracic epidural anesthesia in children as old as 10 yr. Ease of removal of the stylet, ease of injection, and negative aspiration and test doses predict successful placement and obviate the need for routine radiographic confirmation of catheter position. PMID- 1599116 TI - Epidural blood patch in the HIV-positive patient. Review of clinical experience. San Diego HIV Neurobehavioral Research Center. AB - To characterize the natural history of autologous epidural blood patch (EBP) in human immunodeficiency virus (HIV)-seropositive patients, records from an ongoing longitudinal study of the neuropsychological manifestations of HIV infection were retrospectively reviewed. Of 252 participants (218 HIV-seropositive, 34 HIV seronegative) who underwent at least one diagnostic lumbar puncture, 9 (7 seropositive, 2 seronegative) required EBP for post-dural puncture headache. After EBP, 6 of the seropositive subjects underwent serial neuropsychological evaluations over periods ranging from 6 to 24 months; none of these six subjects had a decline in neurocognitive performance or other adverse neurologic or infectious sequelae. We were unable to identify morbidity attributable to EBP in the HIV-seropositive patient followed for as long as 2 yr. PMID- 1599117 TI - Cardiopulmonary bypass does not alter canine enflurane requirements. AB - This study determined the effect of cardiopulmonary bypass (CPB) on canine enflurane minimum alveolar concentration (MAC). Fourteen dogs were anesthetized with enflurane in N2O and O2, and after tracheal intubation, the N2O was discontinued. Femoral arterial and pulmonary arterial catheters were placed, and MAC was determined with the tail-clamp method. CPB was initiated via the femoral artery-vein route, with additional venous return obtained from an external jugular vein. Partial CPB was used in the first 10 dogs. In 4 dogs, a membrane oxygenator (group 1) was used, and in the next 6 dogs a bubble oxygenator (group 2) was used. In 4 additional dogs (group 3), using bubble oxygenators, total CPB was achieved by occlusion of the pulmonary artery via a left thoracotomy. The CPB circuit was primed with Ringer's lactate, and circuit blood flows were 70-125 ml.kg-1.min-1, with mean arterial pressures maintained at 50-110 mmHg. MAC was determined again after termination of CPB. In 10 dogs, MAC was also measured during CPB. In 5 dogs MAC was measured after administration of protamine. MAC in all 14 dogs did not change (2.2 +/- 0.3 vs. 2.3 +/- 0.3). MAC remained constant in group 1 (2.4 +/- 0.3 vs. 2.3 +/- 0.4), group 2 (2.2 +/- 0.2 vs. 2.3 +/- 0.3), and group 3 (2.2 +/- 0.1 vs. 2.3 +/- 0.1). Similarly, MAC was unchanged during CPB (2.2 +/- 0.2 vs. 2.2 +/- 0.2) and after protamine (2.3 +/- 0.2 vs. 2.2 +/- 0.3). Temperature was 38.3 +/- 1.2 prebypass and 37.9 +/- 0.9 postbypass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599118 TI - Effects of pentobarbital on heterosegmentally activated dorsal root depolarization in the rat. Investigation by sucrose-gap technique in vivo. AB - Slow positive cord dorsum (P-) potentials activated by segmental stimulation are believed to reflect primary afferent depolarizations and have been shown to be augmented by barbiturates. However, there have been no data to confirm whether heterosegmentally activated P-potentials also represent primary afferent depolarizations and are similarly affected by barbiturates. We therefore tested whether heterosegmental P-potentials reflect primary afferent depolarizations and how these heterosegmental potentials are affected by barbiturates. Heterosegmentally activated dorsal root (DR) depolarizations (depolarizations evoked in DRs of lumbar segments in response to afferent volleys to cervical segments produced by electrical stimulation of the forepaw) and P-potentials were simultaneously recorded, adapting the sucrose-gap technique for recording DR depolarization in vivo in the rat. Forepaw (heterosegmental) stimulations produced a large depolarization in the DRs of L5-S1 as well as a slow P-potential in the lumbosacral enlargement. Transection of the spinal cord at the level of C1 C2 abolished both the P-potential and DR depolarization activated by heterosegmental stimulation as well as the second component of segmentally (hind paw) activated P-potential. Bicuculline (100 micrograms/kg, intravenous) augmented the P-potential and DR depolarization produced by heterosegmental stimulation, but larger doses, 400-600 micrograms/kg, eventually suppressed these. However, the drug, in a dose-dependent manner, suppressed both the P potential and DR depolarization produced by the segmental stimulation. Pentobarbital (10-40 mg/kg, intravenous) suppressed in a dose-dependent manner both the heterosegmental P-potential and heterosegmental DR depolarization and prolonged their peak latencies. By contrast, pentobarbital augmented and prolonged the segmental P-potential and segmental DR depolarization.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599115 TI - Effects of bolus administration of ORG-9426 in children during nitrous oxide halothane anesthesia. AB - ORG-9426 is a new steroidal nondepolarizing neuromuscular blocking drug. We determined the dose-response relationship of ORG-9426 in 62 children (aged 1-5 yr) during nitrous oxide-halothane anesthesia by means of log-probit transformation and least-squares linear regression of the initial dose and response. Twelve additional patients received a bolus of 600 micrograms/kg (2 X the dose estimated to produce 95% depression of neuromuscular function [ED95]) of ORG-9426. Neuromuscular blockade was monitored by recording the electromyographic activity of the adductor pollicis muscle resulting from supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s at 10-s intervals. To determine the dose response relationship, patients randomly received initial bolus doses of 120 (n = 15), 160 (n = 16), 200 (n = 16), or 240 (n = 15) micrograms/kg ORG-9426. The resulting dose estimated to produce 50% depression of neuromuscular function (ED50) and ED95 were 179 and 303 micrograms/kg, respectively. Time from administration of 600 micrograms/kg to onset of 90% and 100% neuromuscular block was 0.8 +/- 0.1 (0.5-1.3) and 1.3 +/- 0.2 (0.7-2.8) min. The time to recovery of neuromuscular transmission to 25% (T25) was 26.7 +/- 1.9 (17.2-39.0) min. The recovery index (T25-75) was 11.0 +/- 1.6 (6.0-22.8) min, and the time to complete recovery of the magnitude of the fourth response to a train-of-four stimuli divided by the magnitude of the first response (T4/T1) greater than or equal to 0.75 was 41.9 +/- 3.2 (26.5-57.7) min.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599119 TI - Intraarterial propofol is not directly toxic to vascular endothelium. AB - To determine if accidental intraarterial injection of propofol results in vascular damage, the effect of bolus administration of propofol on vascular smooth muscle and the endothelium was investigated using the isolated rabbit ear artery. Ear artery segments, removed from urethane anesthetized rabbits, were perfused with Krebs solution (1 ml.min-1) and pressurized to 60 mmHg before being constricted with extraluminal norepinephrine (1.8-4.2 x 10(-6) M). The external diameter of the vessel was measured by an array of light-dependent diodes. Functional responsiveness was determined by the degree of constriction to norepinephrine and the subsequent dilatation of the artery to intraluminal acetylcholine (2 x 10(-6) M) and glyceryl trinitrate (2 x 10(-6) M), and by the myogenic reactivity to a pressure increase from 60 to 100 mmHg. These responses were measured before and after perfusion with 1% propofol for 120 s. Administration of propofol did not result in any vasoactivity nor did it increase the sensitivity to norepinephrine. Vessels maintained their capacity to dilate to both agents, while the myogenic activity was unaffected. Histologic examination of the propofol exposed vessels showed no changes to smooth muscle structure, and the endothelial layer remained intact. PMID- 1599120 TI - The influence of isoflurane on the vascular reflex response to lung inflation in dogs. AB - Positive pressure ventilation can affect hemodynamic stability by neuroreflex mediated activity. Inhalational anesthesia is known to attenuate the arterial baroreflex function; however, little information is known about the effect of volatile anesthetics on the lung inflation reflex. The influence of isoflurane on static lung inflation reflex-induced changes in venous capacitance and systemic resistance was investigated in dogs. After controlling carotid sinus pressure at 50 mmHg and initiating total cardiopulmonary bypass, the lungs were inflated to tracheal pressures of 10 and 20 mmHg. The systemic vascular resistance index (SVRI) decreased by 0.04 +/- 0.03 and 0.13 +/- 0.03 mmHg.kg.min.ml-1 during tracheal inflation pressures of 10 and 20 mmHg, respectively. There as an accompanying change in systemic vascular capacitance index (SVCI) by 1.0 +/- 0.65 and 3.3 +/- 0.82 ml.kg-1 during tracheal inflation pressures of 10 and 20 mmHg. The addition of isoflurane decreased the reflex vascular response to lung inflation in a dose-dependent manner. A concentration of 1 MAC isoflurane administered via the cardiopulmonary bypass machine attenuated the change in SVRI to tracheal inflation pressures of 10 and 20 mmHg by 75% and 67%, respectively. Isoflurane at 1 MAC also reduced the reflex capacitance response to tracheal pressures of 10 and 20 mmHg by 36% each. Lung inflation-induced changes in SVRI and SVCI were abolished at isoflurane concentrations of 2 MAC. We conclude that under the conditions of this study, 1 MAC isoflurane was shown to attenuate lung reflex-induced changes in SVRI and SVCI and that at higher isoflurane concentrations (2 MAC) these reflex-induced changes were not seen. PMID- 1599121 TI - Comparative effects of halothane, enflurane, and isoflurane at equihypotensive doses on cardiac performance and coronary and renal blood flows in chronically instrumented dogs. AB - In order to compare equihypotensive effects of the three available volatile anesthetics, halothane, enflurane, and isoflurane, dogs were chronically instrumented for measurement of: arterial, left ventricular, and left atrial blood pressures; rate of rise of left ventricular blood pressure; myocardial wall thickening (pulsed Doppler); cardiac output (pulmonary artery electromagnetic flow meter); and coronary and renal blood flows (pulsed Doppler flow meters). All three anesthetics were administered on different days in random order to each dog (n = 10) at doses necessary to decrease mean arterial pressure to 70 and 45 mmHg and two intermediate arterial blood pressures. Changes in cardiac function and regional blood flows were compared to the awake resting state and between anesthetics using analysis of variance and paired t tests. All three anesthetics produced increases in heart rate and decreases in left ventricular dP/dt, myocardial thickening fraction, and stroke volume with the hypotension. The decreases in cardiac performance were similar among the anesthetics except at the high dose (mean arterial pressure = 45 mmHg). During this profound hypotension, cardiac performance was better maintained during isoflurane anesthesia and most depressed by enflurane anesthesia. Coronary and renal blood flows were well preserved with all three anesthetics even at mean arterial pressures of 45 mmHg. Our results suggest that isoflurane may be more beneficial than halothane or enflurane for producing profound intentional hypotension (less than 50 mmHg mean arterial pressure), although extrapolation from animal experiments to the clinical situation should be used with caution. PMID- 1599123 TI - Effect of a VH81X-expressing IgM antibody on early B-cell development. PMID- 1599122 TI - Evidence for a developmental relationship between CD5+ B-lineage cells and macrophages. PMID- 1599124 TI - Major histocompatibility complex controls clonal proliferation of CD5 B cells in H-2-congenic New Zealand mice. PMID- 1599125 TI - Development of gamma delta T-cell subsets from fetal hematopoietic stem cells. AB - Hematopoietic stem cells (HSC) were isolated from mouse fetus, and their developmental potential was compared with adult HSC. Donor-derived V gamma 3+T cells were detected in fetal thymic lobes, repopulated in vitro with fetal liver HSC, but not in those with adult bone marrow HSC. Single clonogenic fetal HSC gave rise to thymic progeny that include V gamma 3+, other gamma delta+, and alpha beta+ T cells. No V gamma 3+ T cells were detected in adult thymus injected intrathymically with either fetal or adult HSC. These results support a hypothesis that only fetal HSC have the capacity to differentiate into V gamma 3+ T cells in the fetal thymic microenvironment, and that the developmental potential of HSC may change during ontogeny. PMID- 1599126 TI - IL-5 responsive subsets among normal and lymphomatous murine B cells. AB - Two normal murine B-cell subpopulations, germinal center and coelomic B cells, and at least some of the lymphomas derived from them, respond to IL-5. In the case of normal B cells, a comitogen (DxS) is required. IFN-gamma is strongly inhibitory to proliferation of the coelomic B-cell subset but not for germinal center cells or the SJL lymphomas derived from them. PMID- 1599128 TI - Molecular mechanisms involved in the generation of diversity. PMID- 1599127 TI - Function and control of recombination-activating gene activity. AB - The RAG-1 and RAG-2 genes synergistically confer VDJ recombinase activity to nonlymphoid cell lines. To unequivocally test RAG gene function, we created lines of mice that lack functional copies of these genes. Consistent with the possibility that RAG gene encode the tissue-specific components of VDJ recombinase, RAG-2-deficient mice are viable but have a severe combined immune deficiency due to inability to initiate VDJ recombination and thereby generate mature lymphocytes. RAG-2-deficient mice have no obvious defect in any tissue or lineage other than lymphocytes, indicating that VDJ recombinase activity and RAG 2-gene function is required only for lymphocyte development. Levels of RAG-1 and RAG-2 expression in primary murine lymphoid tissues and lymphoid bone marrow cultures generally are much higher than those of transformed precursor B-cell lines. Low-level RAG gene expression in permanent cell lines results from a decline during propagation due to outgrowth of cells with lower RAG expression levels. The low and variable level of RAG gene expression in transformed pre-B cell lines correlates with low and variable rates of endogenous VDJ recombination; therefore, such lines are not reliable models for experiments aimed at studying mechanisms that target this activity to particular variable region gene segments. To generate such a system, we introduced RAG genes into B lineage lines under the control of a heat shock-inducible promoter; heat-shock treatment induces extremely high-level but transient RAG expression accompanied by parallel induction of VDJ recombinase activity. Such cells efficiently rearrange transfected VDJ recombination substrates in a regulated manner that is dependent on the activity of transcriptional control elements associated with the target V gene segments. PMID- 1599129 TI - Idiotypic regulation of development of the B-cell repertoire. AB - The mouse B-cell repertoire develops from a restricted set to an extremely diverse set of specificities. Establishment of some of the B-cell clones that constitute the adult repertoire is facilitated and guided by idiotype-directed interactions among complementary sets of B cells early during ontogeny. Through in vivo experiments described here and reported elsewhere, we have shown that the program of B-cell development involving idiotypic interactions is obligatory in the development of certain B cells that provide immunity against bacterial infections. Furthermore, this program of B-cell development is facilitated in newborn mice and not in adult mice that have been transplanted with progenitor cells from adult bone marrow. Thus the idiotype-directed selection of the adult B cell repertoire appears to be limited to fetal-neonatal stages of development. PMID- 1599130 TI - Autoantibodies to phosphatidylcholine. The murine antibromelain RBC response. AB - The observation that murine B-cell populations can contain relatively large numbers of cells that produce IgM with the ability to lyse bromelain-treated mouse erythrocytes (BrMRBC), but not normal untreated MRBC, was made nearly 20 years ago. The major observations regarding the antigen specificity, the cells that produce this IgM, and the immunoglobulin V genes that encode them are summarized in this report. The epitope on BrMRBC that is recognized has been identified as the head group of phosphatidylcholine (PtC); B cells whose IgM has this specificity can be easily identified by their ability to bind fluorescent synthetic liposomes whose membrane contains PtC. The cells producing IgM specific for PtC all derive from the Ly-1 B-cell subset, and they use primarily two VH/VL gene pairs to encode the anti-PtC antibodies. The VH genes used describe two new VH gene families, VH11 and VH12. The genes encoding anti-PtC are unmutated and have characteristics and restricted VDJ constructions. The cells with this specificity, within individual mice, are polyclonal. These criteria are consistent with a primary antigen-driven clonal selection mechanism as the basis for the development of this immune specificity. PMID- 1599131 TI - Evolutionary development of the B-cell repertoire. PMID- 1599132 TI - Analysis of VH251 gene mutation in chronic lymphocytic leukemia (CLL) and normal B-cell subsets. AB - B-cell chronic lymphocytic leukemia (CLL) is the malignant, monoclonal equivalent of a human CD5+ B cell. Previous studies have shown that the VH and VL genes rearranged and/or expressed in CLL have low and random mutations. In this study, however, we have found that the rearranged VH251 gene, one of the three-membered VH5 family, has extensive and selective mutations in B-CLL cells. Somatic mutation at the nucleotide level is 6.03%, and there is a high ratio of replacement to silent mutation in CDRs relative to FWRs. CDR1 mutation is particularly prevalent, and interchanges often lead to acquisition of charge. In VH251 rearranged in CD5+ and CD5- cord-blood B cells, adult peripheral-blood B cells and EBV-transformed CD5+ B-cell lines, the somatic mutation levels are much lower (0.45%, 0.93%, and 1.92%, respectively) with concomitantly lower replacement to silent ratios in CDRs relative to FWRs. The extensive and highly selective somatic mutation of VH251 used in CD5+ CLL cells strongly suggests that part of CLL is generated under the influence of antigen selection and stimulation. PMID- 1599133 TI - c-myc, MHCI, and NK resistance in immunodeficiency lymphomas. PMID- 1599134 TI - Evidence for increased levels of circulating antiphospholipid autoantibodies in patients undergoing in vitro fertilization treatment. PMID- 1599135 TI - The delayed acquisition of antigen-processing distinguishes immature B cells in adults and neonates. PMID- 1599136 TI - Sensing and Controlling Motion--Vestibular and Sensorimotor Function. Proceedings of a conference. July 7-11, 1991, Palo Alto, California. PMID- 1599137 TI - Morphological and electrophysiological properties of hair cells in the bullfrog utriculus. PMID- 1599138 TI - Somatic versus vestibular gravity reception in man. AB - In order to assess the effect of extravestibular gravity receptors on perception and control of body position against that of the otoliths, the subject (S) is exposed to gravitoinertial forces along the spinal (Z) axis on a tiltable board and on a sled centrifuge. It turns out that (1) both effects, on average, are equally strong, although with considerable variance between Ss; (2) the centroid of the mass(es) governing the somatic receptors lies near the centroid of the body; and (3) somatic gravity reception contains two distinctly different systems. Both appear unimpaired in paraplegic Ss with total bilateral sensory loss (TSL) from the 5th to the 1st lumbar spinal segment. One, the truncal system, is eliminated with TSL from the 11th thoracic segment upwards. Yet another is still functioning with TSL up to and including the 6th cervical segment, with the same effectiveness throughout this range. Hence it must be mediated by vagal or, less likely, sympathetic afference, that is, probably, by the influence of gravity on the cardiovascular system. That the afference of the truncal system appears to enter the cord at the last two thoracic segments supports earlier conjectures about a supererogatory static function of the kidneys. In fact, on the tiltable board, 7 bilaterally nephrectomized Ss behaved like paraplegics with TSL between T11 and C6, yet differed significantly in the predicted direction from the normal controls. PMID- 1599139 TI - Spatial orientation of the vestibular system. AB - 1. A simplified three-dimensional state space model of visual vestibular interaction was formulated. Matrix and dynamical system operators representing coupling from the semicircular canals and the visual system to the velocity storage integrator were incorporated into the model. 2. It was postulated that the system matrix for a tilted position was a composition of two linear transformations of the system matrix for the upright position. One transformation modifies the eigenvalues of the system matrix while another rotates the pitch and roll eigenvectors with the head, while maintaining the yaw axis eigenvector approximately spatially invariant. Using this representation, the response characteristics of the pitch, roll, and yaw eye velocity were obtained in terms of the eigenvalues and associated eigenvectors. 3. Using OKAN data obtained from monkeys and comparing to the model predictions, the eigenvalues and eigenvectors of the system matrix were identified as a function of tilt to the side or of tilt to the prone positions, using a modification of the Marquardt algorithm. The yaw eigenvector for right-side-down tilt and for downward pitch cross-coupling was approximately 30 degrees from the spatial vertical. For the prone position, the eigenvector was computed to be approximately 20 degrees relative to the spatial vertical. For both side-down and prone positions, oblique OKN induced along eigenvector directions generated OKAN which decayed to zero along a straight line with approximately a single time constant. This was verified by a spectral analysis of the residual sequence about the straight line fit to the decaying data. The residual sequence was associated with a narrow autocorrelation function and a wide power spectrum. 4. Parameters found using the Marquardt algorithm were incorporated into the model. Diagonal matrices in a head coordinate frame were introduced to represent the direct pathway and the coupling of the visual system to the integrator. Model simulations predicted the behavior of yaw and pitch OKN and OKAN when the animal was upright, as well as the cross-coupling in the tilted position. The trajectories in velocity space were also accurately simulated. 5. There were similarities between the monkey eigenvectors and human perception of the spatial vertical. For side-down tilts and downward eye velocity cross coupling, there was only an Aubert (A) effect. For upward eye velocity cross coupling there were both Muller (E) and Aubert (A) effects. The mean of the eigenvectors for upward and downward eye velocities overlay human 1 x g perceptual data.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599140 TI - Effect of head orientation and position on vestibuloocular reflex adaptation. PMID- 1599142 TI - Floccular contribution to signal processing in the rabbit vestibular nucleus. PMID- 1599141 TI - Three-dimensional transformations from vestibular and visual input to oculomotor output. PMID- 1599143 TI - The algebra of neural response vectors. PMID- 1599144 TI - Neuronal correlates of optic flow stimulation. AB - Neurons in a region of monkey extrastriate cortex, MSTd, respond to the components of optic flow stimulation. Some of these neurons (single-component neurons) are selective for a single type of motion such as inward- or outward radial motion. Other neurons respond to multiple types of rotation, for example, rightward planar, clockwise circular, and inward radial. Rather than forming discrete groups, we think these neurons represent a continuum covering the range from single-component sensitivity to multiple-component sensitivity. By combining the optic flow stimuli, we have also been able to recognize that such combinations alter the response of cells in the continuum to varying degrees. At this point, while our evidence is consistent with the hypothesis that cells in area MSTd contribute to the processing of optic flow stimuli, we do not know whether these neurons do in fact serve this function. As in all single-cell recording experiments, even those in awake animals performing tasks closer to real-world tasks than we have succeeded in emulating here, the activity of the cell in relationship to the visual stimulation is simply a correlate of the optic flow stimulation and may or may not contribute to the processing of optic flow stimulation upon which behavior depends. Further information on a number of characteristics of these cells might clarify their role. Information on such factors as whether heading in the environment is conveyed by individual neurons, or whether this property is more likely to be conveyed over a population of neurons, and the role of changes in the point of fixation of the eyes are critical points. Generation of behavior on the basis of the optic flow stimulation and determination that this behavior is modified by selective lesion of MSTd would also strengthen the argument that visual motion processing in this area is related to analyzing optic flow information. PMID- 1599145 TI - Ocular compensation for self-motion. Visual mechanisms. AB - In monkeys, there are several reflexes that generate eye movements to compensate for the observer's own movements. Two vestibuloocular reflexes compensate selectively for rotational (RVOR) and translational (TVOR) disturbances of the head, receiving their inputs from the semicircular canals and otolith organs, respectively. Two independent visual tracking systems that deal with residual disturbances of gaze are manifest in the two components of the optokinetic response: the indirect or delayed component (OKNd) and the direct or early component (OKNe). We hypothesize that OKNd--like the RVOR--is phylogenetically old, being found in all animals with mobile eyes, and that it evolved as a backup to the RVOR to compensate for rotational disturbances of gaze. Indeed, optically induced changes in the gain of the RVOR result in parallel changes in the gain of OKNd, consistent with the idea of shared pathways as well as shared functions. In contrast, OKNe--like the TVOR--seems to have evolved much more recently in frontal-eyed animals and, we suggest, acts as a backup to the TVOR to deal primarily with translational disturbances of gaze. Frontal-eyed animals with good binocular vision must be able to keep both eyes directed at the object of regard irrespective of proximity, and in order to achieve this during translational disturbances, the output of the TVOR is modulated inversely with the viewing distance. OKNe shares this sensitivity to absolute depth, consistent with the idea that it is synergistic with the TVOR and shares some of its central pathways. There is evidence that OKNe is also sensitive to relative depth cues such as motion parallax, which we suggest helps the system to segregate the object of regard from other elements in the scene. However, there are occasions when the global optic flow cannot be resolved into a single vector useful to the oculomotor system (e.g., when the moving observer looks towards the direction of heading). We suggest that on such occasions a third independent tracking mechanism, the smooth pursuit system, is deployed to stabilize gaze on the local feature of interest. In this scheme, the pursuit system has an attentional focusing mechanism that spatially filters the visual motion inputs driving the oculomotor system. The major distinguishing features of the 3 visual tracking mechanisms are summarized in Table 1. PMID- 1599146 TI - Linear vestibuloocular reflex during motion along axes between nasooccipital and interaural. AB - Linear vestibuloocular reflexes (LVORs) stabilize retinal images by producing eye movements to compensate for linear head motion. LVOR response characteristics depend upon gaze relative to the motion axis and binocular fixation distance. LVOR sensitivity during NO-axis motion increases as gaze eccentricity relative to the motion axis increases and as binocular fixation distance decreases. To fixate targets during forward head motion and rightward gaze, eyes must move to the right, but when looking left, the eyes must move to the left. In this study, LVORs were measured (binocular search coils) during 5.0 Hz horizontal motion along axes between and including NO and IA. This reorients head and otolith inputs relative to linear motion. We found that LVORs follow the same kinematics regardless of eye position in the head or head orientation relative to motion. Eye position information must be quickly and accurately integrated with otolith inputs to determine eye position (gaze) relative to linear head motion in space. The LVOR provides a behaviorally useful reflex for maintaining ocular fixation on visual targets during translation along any axis. PMID- 1599147 TI - Mislocalizations of visual elevation and visual vertical induced by visual pitch: the great circle model. AB - The elevation visually perceived as eye level (VPEL) changes linearly with the pitch of an illuminated visual field. The magnitude of influence is only slightly less when the visual field contains only two dim vertical lines in darkness than when it is complexly structured and normally illuminated. Pitching a visual field consisting of only a single line in darkness produces an influence that is only slightly smaller than the 2-line stimulus. The slopes of the VPEL-vs.-pitch functions for the complex room, 2-line stimulus, and 1-line stimulus are +0.63, +0.56, and +0.52 respectively. Although VPEL is systematically influenced by the pitch of the 2-line stimulus, the orientation of a small line within a frontal plane that is visually perceived as vertical is unaffected. However, when the two lines are pitched by equal amounts in opposite directions, the offset of VPV from true vertical changes linearly with pitch magnitude but VPEL is unaffected. These results are identical to those obtained when the two vertical lines are rolled within the frontal plane, a result that depends on some identities between roll and pitch: roll of two parallel lines in the same direction influences VPV but not VPEL; roll of the two lines in opposite directions influences VPEL but not VPV. The interaction between stimulus conditions and discriminations demonstrates that separate mechanisms are in control of VPEL and of VPV. The slope of the VPEL vs.-pitch function increases exponentially with line length for the 1-line stimulus (space constant = 15.1 degrees). Summation of influences on VPEL for two lines horizontally separated by 50.3 degrees is as great as for two coextensive lines. The above results are predicted from the Great Circle Model which assumes (1) central projection on a spherical approximation to an erect stationary eye; (2) the sign and magnitude of influence of each line on VPEL and on VPV are determined by the direction and magnitude of the separation between the upper pole of the spherical eye and the intersection of the great circle containing the line's image with the central vertical retinal meridian and with the midfrontal retinal meridian, respectively; (3) the influence of individual nonparallel lines is determined by a weighted average of the influences of individual sets of parallel lines; (4) a generalized version of the Great Circle Model is indicated in which extraretinal signals from head and eye are taken into account. PMID- 1599148 TI - Visual signals in the nucleus of the optic tract and their brain stem destinations. PMID- 1599149 TI - The nucleus of the optic tract. Its function in gaze stabilization and control of visual-vestibular interaction. AB - 1. Electrical stimulation of the nucleus of the optic tract (NOT) induced nystagmus and after-nystagmus with ipsilateral slow phases. The velocity characteristics of the nystagmus were similar to those of the slow component of optokinetic nystagmus (OKN) and to optokinetic after-nystagmus (OKAN), both of which are produced by velocity storage in the vestibular system. When NOT was destroyed, these components disappeared. This indicates that velocity storage is activated from the visual system through NOT. 2. Velocity storage produces compensatory eye-in-head and head-on-body movements through the vestibular system. The association of NOT with velocity storage implies that NOT helps stabilize gaze in space during both passive motion and active locomotion in light with an angular component. It has been suggested that "vestibular-only" neurons in the vestibular nuclei play an important role in generation of velocity storage. Similarities between the rise and fall times of eye velocity during OKN and OKAN to firing rates of vestibular-only neurons suggest that these cells may receive their visual input through NOT. 3. One NOT was injected with muscimol, a GABAA agonist. Ipsilateral OKN and OKAN were lost, suggesting that GABA, which is an inhibitory transmitter in NOT, acts on projection pathways to the brain stem. A striking finding was that visual suppression and habituation of contralateral slow phases of vestibular nystagmus were also abolished after muscimol injection. The latter implies that NOT plays an important role in producing visual suppression of the VOR and habituating its time constant. 4. Habituation is lost after nodulus and uvula lesions and visual suppression after lesions of the flocculus and paraflocculus. We postulate that the disappearance of vestibular habituation and of visual suppression of vestibular responses after muscimol injections was due to dysfacilitation of the prominent NOT-inferior olive pathway, inactivating climbing fibers from the dorsal cap to nodulouvular and flocculoparafloccular Purkinje cells. The prompt loss of habituation when NOT was inactivated, and its return when the GABAergic inhibition dissipated, suggests that although VOR habituation can be relatively permanent, it must be maintained continuously by activity of the vestibulocerebellum. PMID- 1599150 TI - Velocity storage in labyrinthine disorders. AB - We studied 13 patients with unilateral peripheral vestibular lesions following removal of acoustic neurinomas. The time constant of the VOR after surgery was 6.4 +/- 2.6 seconds (normal is 18.5 +/- 7.7 seconds). The time constant of OKAN after surgery was 7.2 +/- 1.8 seconds (normal is 11.3 +/- 3.2 seconds). The mean initial velocity of OKAN after surgery was 9.7 +/- 2.4 deg/second (normal is 11.7 +/- 5.9 deg/second). These data suggest that unilateral peripheral vestibular loss is associated with a complete loss of velocity storage for canal input but only a partial loss of velocity storage for visual input. These results can be accounted for by current mathematical models of the velocity storage mechanism. PMID- 1599152 TI - Perception of motion and position relative to the earth. An overview. AB - Results of the five experiments are consistent with the following generalizations. Canal-mediated turn perception (pitch, roll, or yaw) in earth horizontal or earth-vertical plane, is suppressed in direct relationship to the magnitude of a linear acceleration vector lying in the plane of a responding canal when the magnitude of the linear vector is constant or increasing and when its direction is either fixed or rotating in the same direction as the concomitant canal signal. Canal-mediated turn perception (pitch, roll, or yaw) is not suppressed by a coplanar linear vector that is counterrotating relative to the canal signal. Change in perceived attitude (pitch, roll, or yaw) is very sluggish in the absence of concordant canal information; attitude change may not be an immediate otolith-mediated perceptual event but a slowly developing perception dependent upon cognitive appreciation of an immediate otolith angular position signal. Otolith phasic neural units, unreinforced by appropriate canal signals, may contribute more to a brief linear velocity component in perception than to rate of attitude change. Otolith-mediated attitude perception within a given earth-vertical plane can be distorted by strong coplanar angular velocity canal information. Once distorted, return to veridical attitude perception can be gradual because, in the absence of complimentary canal or visual information, recovery is dependent upon relatively slow cognitive appreciation of a prevailing otolith position signal. Several attractive hypotheses relating to the dynamics of attitude perception can only be tested by substantially more data on the dynamics of spatial orientation perception. Most of our objectives cannot be achieved without models that yield valid prediction of the dynamics of spatial orientation perception. All of the observations in these experiments were carried out in darkness, or, in the simulated catapult experiment, without external visual reference. Various forms of visual information will change the dynamics of spatial orientation perception. My discussion has been limited to consideration of the vestibular system, as though the canal and otolith systems completely controlled the dynamics of spatial orientation perceptions. Obviously other partners in the dynamics of postural control, including vision, proprioception, and expectation, must be included in this challenging field of research. Dedication to stereotyped ideas about objectivity in the 20th century has hindered advancement of knowledge on the dynamics of spatial orientation perception relative to rate of progress achieved by several scientists of the 18th and 19th centuries, who provided word pictures of perceived motions and tilts along with descriptions of the motions that engendered the pictures.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599153 TI - Sense of body position in parabolic flight. PMID- 1599151 TI - High-frequency vestibuloocular reflex as a diagnostic tool. AB - During locomotion, the head is subject to rotational perturbations with fundamental frequencies in the range 0.5-5.0 Hz, and significant harmonics up to 20 Hz. Patients who have lost labyrinthine function complain of oscillopsia and visual impairment during locomotion. Measurements of head movements during walking and running in place in such patients indicate that head stability is similar to that in normal subjects. Therefore, head stability is mainly guaranteed by mechanical, not neurogenic, factors. On the other hand, the visual symptoms of such patients can be ascribed to instability of gaze. Thus, it seems that other mechanisms such as visual following, the cervicoocular reflex, or anticipatory eye movements cannot compensate for loss of the VOR during locomotion (though they may do so for lower-frequency or active head rotations). The indispensable role of the VOR during locomotion is probably a reflection of its short latency (16 mseconds or less in the horizontal and vertical planes), which guarantees short phase lags during high-frequency head rotations. Our results indicate that laboratory testing of patients with vestibular symptoms should employ stimuli that correspond to those occurring during locomotion. PMID- 1599154 TI - Multisensory integration in microgravity. PMID- 1599155 TI - Perception and action in altered gravity. PMID- 1599156 TI - Patterns of connectivity in the vestibular nuclei. PMID- 1599157 TI - Responses of vestibular and prepositus neurons to head movements during voluntary suppression of the vestibuloocular reflex. AB - Neurons in the vestibular nuclei and the prepositus nucleus exhibited several different types of changes in their firing behavior during voluntary cancellation of the horizontal VOR. The head velocity sensitivity of type I position vestibular-pause neurons was reduced during cancellation, while type II vestibular neurons exhibit an increase in their sensitivity. The firing behavior of burst tonic neurons in the medial vestibular nucleus, the prepositus nucleus, like the cells in the abducens nucleus, was closely related to the eye movements generated when the VOR is cancelled. Other cells in the PH and MVN respond primarily to smooth pursuit eye movements. We suggest that the behavior of abducens neurons during the VOR and during VOR cancellation can be explained if they receive inputs from PVP neurons, burst tonic neurons, and smooth pursuit neurons. PMID- 1599158 TI - Vestibular and visual interaction in generation of rapid eye movements. PMID- 1599159 TI - Effects of ibotenic acid lesions of nucleus prepositus hypoglossi on optokinetic and vestibular eye movements in the alert, trained monkey. PMID- 1599160 TI - Climbing fiber intervention blocks plasticity of the vestibuloocular reflex. PMID- 1599161 TI - Otolith-ocular testing in human subjects. AB - Assessment of the otolith-ocular reflex of human subjects involves linear acceleration and/or changes in the orientation of the head with respect to gravity. Several such stimuli are currently under investigation regarding their applicability to the evaluation of patients with dizziness and balance disorders. Discussed in this paper are off-vertical axis rotation, eccentric rotation, pitch and roll rotation, and linear acceleration. For each of these stimuli, basic principles, normative human data, and patient data are described. Although none of these methods are currently established for clinical use, each of them, especially off-vertical axis rotation and linear acceleration, have the potential for developing into a clinically useful method for assessing otolith function in man. PMID- 1599162 TI - Central organization and modeling of eye-head coordination during orienting gaze shifts. PMID- 1599163 TI - Cortical control of vestibular memory-guided saccades. PMID- 1599164 TI - Neuronal substrates of spatial transformations in vestibuloocular and vestibulocollic reflexes. PMID- 1599166 TI - Spatial transformation in the vertical vestibulocollic reflex. PMID- 1599168 TI - Cyclorotation of the eyes and subjective visual vertical in vestibular brain stem lesions. PMID- 1599167 TI - Functional synergies of neck muscles innervated by single medial vestibulospinal axons. PMID- 1599165 TI - Filtering properties of hair cells. AB - Three questions were asked about filtering properties of hair cells. First, it was asked if hair cells in different receptors showed different filtering properties to match the receptor response to the particular characteristics of the stimulus? It seems that the answer is yes, since for example, the resonant frequencies of pigeon semicircular hair cells at membrane potentials around the RMP are in a range (12-280 Hz) that could match angular head frequencies. Since critical frequency tuning of one frequency probably is not necessary for the semicircular canals it is quite reasonable that the largest quality factor (Qe) of resonance in pigeon semicircular canal hair cells for membrane potentials around the RMP is 4 times lower than the largest Qe in bullfrog saccular hair cells and 10 times lower than Qe in the turtle basilar papilla. Second, it was asked if hair cells of the same morphological type but in different regions of the neuroepithelium have different filtering properties. It seems that this question needs more careful study since most available data on hair cells that show different filtering properties depending on their location in the neuroepithelium show subtle morphological differences and therefore the hair cells could be classified as different types. Finally, it was asked if different hair cell types (based on morphology and innervation) have different filtering properties. The currents in pigeon and guinea pig type I and type II semicircular canal hair cells, guinea pig inner and outer cochlear hair cells, goldfish short and tall saccule hair cells and chick short and tall cochlea hair cells suggest that the answer to this question is yes. The challenge is to continue to precisely specify the filtering properties of different types of hair cells in different places on the neuroepithelium of different receptors. PMID- 1599169 TI - Enhancement of optokinetic and vestibuloocular responses in the rabbit by cholinergic stimulation of the flocculus. AB - Bilateral microinjections into the cerebellar flocculus of the rabbit of carbachol, a general cholinergic agonist, profoundly affect vestibuloocular (VOR) and optokinetic (OKR) reflexes. For sinusoidal stimuli (0.15 Hz, 5 deg peak to peak), the gain of the OKR was strongly increased, while the gain of the VOR was moderately increased. These effects were partially mimicked by floccular injection of the acetylcholinesterase inhibitor eserine. Floccular injection of the muscarinic blocker atropine significantly lowered the gain of the OKR. The effects of the nicotinic blocker mecamylamine were not significant. Optokinetic nystagmus (OKN) in response to constant stimulus velocities (1-30 deg/second) showed a markedly accelerated buildup and a shortened optokinetic after-nystagmus (OKAN) after floccular injections of carbachol. The steady-state gain of OKN remained unaffected. None of the described effects occurred after floccular injection of the solvent, saline. It is postulated that cholinergic cerebellar afferents, one probable source of which are the vestibular nuclei, enhance the optokinetic and vestibular modulation of floccular Purkinje cells. PMID- 1599170 TI - Oculomotor effects of gamma-aminobutyric acid agonists and antagonists in the vestibular nuclei of the alert monkey. PMID- 1599171 TI - What is motion sickness? PMID- 1599172 TI - The role of prediction in head-free pursuit and vestibuloocular reflex suppression. PMID- 1599173 TI - Self-controlled reorienting movements in response to rotational displacements in normal subjects and patients with labyrinthine disease. PMID- 1599174 TI - The effects of target distance on eye and head movement during locomotion. PMID- 1599175 TI - Plastic changes in the human cervicoocular reflex. PMID- 1599176 TI - Linear acceleration modulates the nystagmus induced by angular acceleration stimulation of the horizontal canal. PMID- 1599177 TI - Validating the hypothesis of otolith asymmetry as a cause of space motion sickness. PMID- 1599178 TI - The human vertical vestibuloocular reflex in response to high-acceleration stimulation after unilateral vestibular neurectomy. PMID- 1599179 TI - Optokinetic and vestibular interactions with smooth pursuit. Psychophysical responses. PMID- 1599180 TI - Recovery of postural equilibrium control following spaceflight. AB - Decreased postural stability is observed in most astronauts immediately following spaceflight. Because ataxia may present postflight operational hazards, it is important to determine the incidence of postural instability immediately following landing and the dynamics of recovery of normal postural equilibrium control. It is postulated that postflight postural instability results from in flight adaptive changes in central nervous system (CNS) processing of sensory information from the visual, vestibular, and proprioceptive systems. The purpose of the present investigation was to determine the magnitude and time course of postflight recovery of postural equilibrium control and, hence, readaptation of CNS processing of sensory information. Thirteen crew members from six spaceflight missions were studied pre- and postflight using a modified commercial posturography system. Postural equilibrium control was found to be seriously disrupted immediately following spaceflight in all subjects. Readaptation to the terrestrial environment began immediately upon landing, proceeded rapidly for the first 10-12 hours, and then proceeded much more slowly for the subsequent 2-4 days until preflight stability levels were reachieved. It is concluded that the overall postflight recovery of postural stability follows a predictable time course. PMID- 1599181 TI - Response of otolith-related neurons in bilateral vestibular nucleus of acute hemilabyrinthectomized cats to off-vertical axis rotations. PMID- 1599182 TI - Responses of direction-selective neurons in monkey cortex to self-induced visual motion. PMID- 1599183 TI - Cerebellar uvula involvement in visual motion processing and smooth pursuit control in monkey. PMID- 1599184 TI - Three-dimensional eye velocity measurement following postrotational tilt in the monkey. PMID- 1599185 TI - A model of responses of horizontal-canal-related vestibular nuclei neurons that respond to linear head acceleration. PMID- 1599186 TI - Preservation of the electrical-evoked vestibuloocular reflex and otolith-ocular reflex in two patients with markedly impaired canal-ocular reflexes. PMID- 1599187 TI - Eye movements in response to canal and otolith signals in opposing directions. PMID- 1599188 TI - The effects of unidirectional visual surround translation on detection of physical linear motion direction. A psychophysical scale for vection. PMID- 1599189 TI - Variation of gravitoinertial force and its influence on ocular torsion and caloric nystagmus. PMID- 1599190 TI - Age-related changes in human smooth pursuit responses to horizontal step-ramp target trajectories. PMID- 1599191 TI - VTM--a new method of measuring ocular torsion using image-processing techniques. PMID- 1599193 TI - Visual-vestibular interaction during high-frequency, active head movements in pitch and yaw. PMID- 1599192 TI - Characterization of yaw to roll cross-coupling in the three-dimensional structure of the velocity storage integrator. PMID- 1599194 TI - Segregation of visual features is not the basis of visual orientation relative to gravity. PMID- 1599195 TI - The influence of head reorientation on the axis of eye rotation and the vestibular time constant during postrotatory nystagmus. PMID- 1599196 TI - Multidimensional descriptions of the optokinetic and vestibuloocular reflexes. PMID- 1599197 TI - The representation of the spatial vertical in human optokinetic nystagmus. AB - With our stimulus conditions we were unable to record more than 2-3 beats of OKAN; therefore direct comparison to the data recorded from monkeys is not possible. We did, however, see cross-coupling in OKN. In monkeys, cross-coupling predominates in OKAN, indicating that velocity storage underlies this phenomenon. We consistently saw the axis of response shift towards the spatial vertical. This implies that although OKAN was weak, velocity storage contributed a representation of the spatial vertical to OKN that is dependent on the axis of the head or body with respect to gravity. PMID- 1599198 TI - Interaction of semicircular canals and otoliths in the processing structure of the subjective zenith. PMID- 1599199 TI - How does the otolith system detect three-dimensional head angular velocity? PMID- 1599200 TI - Vestibular-somatosensory interaction in rapid responses to head perturbations. PMID- 1599201 TI - Dynamic modulation of vestibuloocular reflex gain during passive head rotation. PMID- 1599202 TI - A neural network for computing surface curvature from optic flow. PMID- 1599203 TI - Visual direction is corrected by a hybrid extraretinal eye position signal. PMID- 1599204 TI - The interaction of angular and linear optokinetic stimuli with an angular vestibular stimulus. PMID- 1599205 TI - Optical and somesthetic biases of postural orientation in the pitch dimension. PMID- 1599206 TI - The effect of target distance and stimulus frequency on horizontal eye movements induced by linear acceleration on a parallel swing. PMID- 1599207 TI - Response characteristics of the human torsional vestibuloocular reflex. PMID- 1599208 TI - The effect of scopolamine on the vestibuloocular reflex, gain adaptation, and the optokinetic response. PMID- 1599209 TI - The error signal for modification of vestibuloocular reflex gain. PMID- 1599210 TI - The torsional vestibuloocular reflex can be canceled but not enhanced by visual stimuli. PMID- 1599212 TI - Negative relationships between responses from head-shake and caloric tests. PMID- 1599211 TI - Context-specific gain switching in the human vestibuloocular reflex. PMID- 1599213 TI - Three-dimensional optokinetic responses in man and rabbit. A comparison between a frontal and a lateral eyed species. PMID- 1599215 TI - Gaze control during head-free pursuit in patients with loss of vestibular function. PMID- 1599214 TI - Interactions between otoliths and vision revealed by the response to Z-axis linear movements. PMID- 1599216 TI - Velocity characteristics of smooth eye movements in patients with cerebellar ataxia. PMID- 1599217 TI - Implications of vestibular nucleus neuron rectification for signal processing in the horizontal vestibuloocular reflex. PMID- 1599219 TI - Vestibular afferents innervating the posterior ampullae in a turtle, Pseudemys scripta. PMID- 1599218 TI - Vestibular neurons encoding two-dimensional linear acceleration assist in the estimation of rotational velocity during off-vertical axis rotation. PMID- 1599220 TI - Quantification of different classes of canal-related vestibular nuclei neuron responses to linear acceleration. PMID- 1599221 TI - Structure and function of vestibular nerve fibers in the chinchilla and squirrel monkey. PMID- 1599222 TI - Participation of secondary vestibular neurons in nonvisual mechanisms of vestibuloocular reflex cancellation. PMID- 1599223 TI - Antagonistic otolith-visual units in cat vestibular nuclei. PMID- 1599224 TI - Vestibular efferent system in pigeons. Anatomical organization and effect upon semicircular canal afferent responsiveness. PMID- 1599225 TI - Does counterrolling violate Listing's law? PMID- 1599226 TI - Mechanisms of head stabilization during random rotations in the pitch plane. PMID- 1599227 TI - GABA is an afferent vestibular neurotransmitter in the guinea pig. Immunocytochemical evidence in the utricular maculae. PMID- 1599228 TI - Acceleration detection by vestibular hair cells. Hair bundles as spatially distributed phased-array antennas. PMID- 1599229 TI - Unit activity in the vestibular nuclei of monkeys during off-vertical axis rotation. PMID- 1599230 TI - Patterns of connections between six semicircular canals and neck motoneurons. PMID- 1599231 TI - Vestibular input to visual-tracking neurons in area MST of awake rhesus monkeys. PMID- 1599232 TI - Stimulation and single-unit studies of velocity storage in the vestibular and prepositus hypoglossi nuclei of the monkey. PMID- 1599233 TI - Purification and characterization of an extracellular muramidase of Clostridium acetobutylicum ATCC 824 that acts on non-N-acetylated peptidoglycan. AB - An extracellular enzyme showing lytic activity on non-N-acetylated peptidoglycan has been isolated from Clostridium acetobutylicum ATCC 824. The lytic enzyme was purified to homogeneity by anion-exchange chromatography and gel filtration, with a recovery of 24%. The enzyme was monomeric and had an estimated molecular weight of 41,000 and an isoelectric point of 3.8. It has been characterized as a muramidase whose 23-amino-acid N terminus displayed 39% homology with the N,O diacetyl muramidase of the fungus Chalaropsis sp. The muramidase hydrolyzed purified cell walls at an optimum pH of 3, with a maximum velocity of 9.1 mumol of reducing sugars released min-1 mg of muramidase-1 and a concentration of cell walls giving a half-maximum rate of 0.01 mg ml-1. Its activity was inhibited by glucosamine, N-acetylglucosamine, Hg2+, Fe3+, and Ag+ but not by choline. The muramidase-peptidoglycan complex rapidly dissociated before total hydrolysis of the chain and randomly reassociated on another peptidoglycan chain. The affinity of the muramidase was affected by the protein content and the acetylation of the cell wall. PMID- 1599235 TI - Anaerobic dechlorination of polychlorobiphenyls (Aroclor 1242) by pasteurized and ethanol-treated microorganisms from sediments. AB - A polychlorobiphenyl (PCB)-dechlorinating inoculum eluted from upper Hudson River sediments was treated with either heat or ethanol or both. The treated cultures retained the ability to dechlorinate PCBs (Aroclor 1242) under strictly anaerobic conditions. The dechlorination activity was maintained in serial cultures inoculated with transfers of 1% inoculum when the transferred inoculum was treated each time in the same manner. No methane production was detected in any treated culture, although dechlorination of PCBs in the untreated cultures was always accompanied by methane production. All treated cultures preferentially removed meta chlorines, yielding a dechlorination pattern characterized by accumulation of certain ortho- and para-subsituted congeners such as 2-4 chlorobiphenyl (2-4-CB), 2,4-2-CB, and 2,4-4-CB. In contrast, the untreated cultures showed more extensive dechlorination activities, which almost completely removed both meta and para chlorines from Aroclor 1242. These results suggest that microorganisms responsible for the dechlorination of PCBs in the upper Hudson River sediments can be grouped into two populations according to their responses to the heat and ethanol treatments. Microorganisms surviving the heat and ethanol treatments preferentially remove meta chlorines, while microorganisms lost from the enrichment mainly contribute to the para dechlorination activity. These results indicate that anaerobic sporeformers are at least one of the physiological groups responsible for the reductive dechlorination of PCBs. The selection of a dechlorinating population by such treatments may be an important step in isolation of PCB-dechlorinating microorganisms. PMID- 1599234 TI - Production of poly-(3-hydroxybutyrate-co-3-hydroxyvalerate) in a recombinant Escherichia coli strain. AB - An Escherichia coli strain has been constructed that produces the copolymer poly (3-hydroxybutyrate-co-3-hydroxyvalerate) P(HB-co-HV). This has been accomplished by placing the PHB biosynthetic genes from Alcaligenes eutrophus into an E. coli fadR atoC(Con) mutant and culturing the strain in M9 minimal medium containing glucose and propionate. 3-Hydroxyvalerate incorporation is absolutely dependent on the presence of both glucose and propionate, and 3-hydroxybutyrate-3 hydroxyvalerate ratios in the copolymer can be manipulated by altering the propionate concentration and/or the glucose concentration in the culture. P(HB-co HV) production can be accomplished by using a wide variety of feeding regimens, but the most efficient is to allow the culture to grow to late log phase in minimal medium containing acetate and then add glucose and propionate to initiate copolymer production. A broad range of propionate concentrations can be used in the culture to stimulate 3-hydroxyvalerate incorporation; however, the most efficient utilization of propionate occurs at concentrations below 10 mM. 3 Hydroxyvalerate molar percentages in the copolymer are relatively constant over the course of growth. The copolymer has been purified and confirmed to be P(HB-co HV) by gas chromatography/mass spectrometry and differential scanning calorimetry. PMID- 1599238 TI - Degradation of hydrogen sulfide by Xanthomonas sp. strain DY44 isolated from peat. AB - Xanthomonas sp. strain DY44, capable of degrading H2S, was isolated from dimethyl disulfide-acclimated peat. This bacterium removed H2S either as a single gas or in the presence of the sulfur-containing compounds methanethiol, dimethyl sulfide, and dimethyl disulfide. The maximum specific H2S removal rate, obtained in the late stationary phase, was 3.92 mmol g of dry cells-1 h-1 (6.7 x 10(-16) mol cell-1 h-1) at pH 7 and 30 degrees C through a batch experiment in a basal mineral medium. Since Xanthomonas sp. strain DY44 exhibited no autotrophic growth with H2S, the H2S removal was judged not to be a consequence of chemolithotrophic activity. By using X-ray photoelectron spectroscopy, the metabolic product of H2S oxidation was determined to be polysulfide, which has properties very similar to those of elemental sulfur. Autoclaved cells (120 degrees C, 20 min) did not show H2S degradation, but cells killed by gamma-irradiation and cell extracts both oxidized H2S, suggesting the existence of a heat-labile intracellular enzymatic system for H2S oxidation. When Xanthomonas sp. strain DY44 was inoculated into fibrous peat, this strain degraded H2S without lag time, suggesting that it will be a good candidate for maintaining high H2S removability in the treatment of exhaust gases. PMID- 1599236 TI - Conversion of xylan to ethanol by ethanologenic strains of Escherichia coli and Klebsiella oxytoca. AB - A two-stage process was evaluated for the fermentation of polymeric feedstocks to ethanol by a single, genetically engineered microorganism. The truncated xylanase gene (xynZ) from the thermophilic bacterium Clostridium thermocellum was fused with the N terminus of lacZ to eliminate secretory signals. This hybrid gene was expressed at high levels in ethanologenic strains of Escherichia coli KO11 and Klebsiella oxytoca M5A1(pLOI555). Large amounts of xylanase (25 to 93 mU/mg of cell protein) accumulated as intracellular products during ethanol production. Cells containing xylanase were harvested at the end of fermentation and added to a xylan solution at 60 degrees C, thereby releasing xylanase for saccharification. After cooling, the hydrolysate was fermented to ethanol with the same organism (30 degrees C), thereby replenishing the supply of xylanase for a subsequent saccharification. Recombinant E. coli metabolized only xylose, while recombinant K. oxytoca M5A1 metabolized xylose, xylobiose, and xylotriose but not xylotetrose. Derivatives of this latter organism produced large amounts of intracellular xylosidase, and the organism is presumed to transport both xylobiose and xylotriose for intracellular hydrolysis. By using recombinant M5A1, approximately 34% of the maximal theoretical yield of ethanol was obtained from xylan by this two-stage process. The yield appeared to be limited by the digestibility of commercial xylan rather than by a lack of sufficient xylanase or by ethanol toxicity. In general form, this two-stage process, which uses a single, genetically engineered microorganism, should be applicable for the production of useful chemicals from a wide range of biomass polymers. PMID- 1599237 TI - Differential bioavailability of soil-sorbed naphthalene to two bacterial species. AB - Prediction of the fate of hydrophobic organic contaminants in soils is complicated by the competing processes of sorption and biodegradation. To test the hypothesis that sorbed naphthalene is unavailable to degradative microorganisms, we developed a simple kinetic method to examine the rates and extents of naphthalene degradation in soil-free and soil-containing systems in a comparison of two bacterial species. The method is predicated on the first-order dependence of the initial mineralization rate on the naphthalene concentration when the latter is below the Michaelis-Menten half-saturation constant (Km) for naphthalene for the organism under study. Rates and extents of mineralization were estimated by nonlinear regression analysis of data by using both a simple first-order model and a three-parameter, coupled degradation-desorption model described for the first time here. Bioavailability assays with two bacterial species (Pseudomonas putida ATCC 17484 and a gram-negative soil isolate, designated NP-Alk) gave dramatically different results. For NP-Alk, sorption limited both the rate and extent of naphthalene mineralization, in accordance with values predicted on the basis of the equilibrium aqueous-phase naphthalene concentrations. For strain 17484, both the rates and extents of naphthalene mineralization exceeded the predicted values and resulted in enhanced rates of naphthalene desorption from the soils. We conclude that there are important organism-specific properties which make generalizations regarding the bioavailability of sorbed substrates inappropriate. PMID- 1599239 TI - Physiological and nutritional factors affecting synthesis of extracellular metalloproteases by Clostridium bifermentans NCTC 2914. AB - Extracellular protease production by Clostridium bifermentans NCTC 2914 occurred throughout the growth phase in batch culture. In both glucose-excess and -limited chemostats, protease formation was inversely related to the dilution rate, over the range D = 0.03 to 0.70 h-1. At high dilution rates (D greater than 0.25 h-1), protease activities were greatest under excess glucose conditions. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of chemostat culture effluents showed the presence of up to 18 bands of protease activity at low dilution rates, with apparent molecular masses ranging from about 36 to 125 kDa. High-performance liquid chromatography gel filtration of culture supernatants gave four peaks of activity at 34, 42, 60, and 102 kDa. Glucose, peptone, and phosphate stimulated protease formation, but ammonia concentrations up to 10 g liter-1 had little effect on the process. Culture pH in glucose-excess chemostats strongly influenced protease synthesis, which was maximal during growth at pH 6.4. The optimal pH of protease activity was 7.0. Although a wide variety of proteins were hydrolyzed by C. bifermentans proteases, none of the enzymes were collagenolytic. Of 21 different p-nitroanilide, beta-naphthylamide, and N-carbobenzoyl substrates tested, none were hydrolyzed. With the exception of Ca2+, divalent metal ions inhibited proteolysis. Experiments with protease inhibitors demonstrated that 1 mM EDTA inhibited protease activities in culture supernatants by over 90%, indicating that the enzymes were principally of the metalloprotease type. PMID- 1599240 TI - Efficacy of burning, tillage, and biocides in controlling bacteria released at field sites and effects on indigenous bacteria and fungi. AB - Decontamination treatments of burning and biocide application, alone and in combination with tillage, were evaluated for their ability to reduce populations of bacteria applied to the leaves of plants in field plots. In addition, the effects of these control methods on indigenous leaf and soil bacteria and fungi were assessed. Field plots of bush beans (Phaseolus vulgaris), sprayed with the bacterium Pseudomonas syringae, Pseudomonas fluorescens, or Erwinia herbicola, received the following treatments: (i) control, (ii) tillage, (iii) burning, (iv) burning plus tillage (burn-tillage), (v) Kocide (cupric hydroxide), (vi) Kocide plus tillage, (vii) Agri-Strep (streptomycin sulfate), and (viii) Agri-Strep plus tillage. Leaves and soil from the plots were sampled at 1 day before and at 1, 3, 7, 10, 14, 21, and 30 days after application of the decontamination treatments. The burn and burn-tillage treatments produced the most significant reductions in bacterial populations. The Agri-Strep treatment was more effective than the Kocide treatment in eliminating applied bacteria, but neither biocide produced consistent or persistent control. In contrast, the tillage treatment, alone or in combination with the Agri-Strep or Kocide treatments, had a short-term stimulatory effect and increased populations of applied bacteria and also levels of indigenous fungi and bacteria. Agri-Strep and Kocide treatments caused significant reductions in indigenous bacterial populations up to 14 days after application and in indigenous fungal populations on day 7 after application. Our results suggest that conventional plant disease control methods may not provide satisfactory control of genetically engineered microorganisms and indicate a need for further development of effective and selective methods to control release microorganisms at field sites. PMID- 1599241 TI - Glyphosate degradation by immobilized bacteria: field studies with industrial wastewater effluent. AB - Immobilized bacteria have been shown in the laboratory to effectively remove glyphosate from wastewater effluent discharged from an activated sludge treatment system. Bacterial consortia in lab columns maintained a 99% glyphosate-degrading activity (GDA) at a hydraulic residence time of less than 20 min. In this study, a pilot plant (capacity, 45 liters/min) was used for a field demonstration. Initially, activated sludge was enriched for microbes with GDA during a 3-week biocarrier activation period. Wastewater effluent was then spiked with glyphosate and NH4Cl and recycled through the pilot plant column during start-up. Microbes with GDA were enhanced by maintaining the pH at less than 8 and adding yeast extract (less than 10 mg/liter). Once the consortia were stabilized, the column capacity for glyphosate removal was determined in a 60-day continuous-flow study. Waste containing 50 mg of glyphosate per liter was pumped at increasing flow rates until a steady state was reached. A microbial GDA of greater than 90% was achieved at a 10-min hydraulic residence time (144 hydraulic turnovers per day). Additional studies showed that microbes with GDA were recoverable within (i) 5 days of an acid shock and (ii) 3 days after a 21-day dormancy (low-flow, low maintenance) mode. These results suggest that full-scale use of immobilized bacteria can be a cost-effective and dependable technique for the biotreatment of industrial wastewater. PMID- 1599242 TI - Aerobic vinyl chloride metabolism in Mycobacterium aurum L1. AB - Mycobacterium aurum L1, capable of growth on vinyl chloride as a sole carbon and energy source, was previously isolated from soil contaminated with vinyl chloride (S. Hartmans et al., Biotechnol. Lett. 7:383-388, 1985). The initial step in vinyl chloride metabolism in strain L1 is catalyzed by alkene monooxygenase, transforming vinyl chloride into the reactive epoxide chlorooxirane. The enzyme responsible for chlorooxirane degradation appeared to be very unstable and thus hampered the characterization of the second step in vinyl chloride metabolism. Dichloroethenes are also oxidized by vinyl chloride-grown cells of strain L1, but they are not utilized as growth substrates. Three additional bacterial strains which utilize vinyl chloride as a sole carbon and energy source were isolated from environments with no known vinyl chloride contamination. The three new isolates were similar to strain L1 and were also identified as Mycobacterium aurum. PMID- 1599243 TI - Self-similar colony morphogenesis by gram-negative rods as the experimental model of fractal growth by a cell population. AB - The ability to form a fractal colony was shown to be common among several species of the family Enterobacteriaceae. Bacterial spreading growth in a two-dimensional field of nutrient concentration was indicated to be important for this experimental self-similar morphogenesis. As a basic analogy, the diffusion limited aggregation model was suggested. Fractal dimensions of colonies were mostly in the range of values from 1.7 to 1.8, similar to those of the two dimensional diffusion-limited aggregation model. Bacterial characteristics and culture conditions inducing changes in fractal patterns and growth rates were identified. The contribution of the bacterial multicellular nature to fractal morphogenesis is discussed. PMID- 1599244 TI - Evaluation of aquatic sediment microcosms and their use in assessing possible effects of introduced microorganisms on ecosystem parameters. AB - In this paper we describe a sediment microcosm system consisting of 20 undisturbed, layered sediment cores with overlying site water which are incubated under identical conditions of temperature, light, stirring rate of overlying water, and water exchange rate. Ecosystem parameters (nutrient level, photosynthetic potential, community structure of heterotrophic bacteria, thymidine incorporation rate, and oxygen microgradients) of the laboratory microcosms and the source ecosystem were compared and shown to be indistinguishable for the first 2 weeks. In weeks 3 and 4, small differences were detectable in the nutrient level, community structure of heterotrophic bacteria, and thymidine incorporation rate. However, the photosynthetic potential, depth profiles of heterotrophic bacterial community structure, and oxygen microgradients were maintained throughout the incubation period and did not differ between laboratory microcosms and the source ecosystem. The microcosm system described here would thus appear to be a valid model of aquatic sediments for up to 4 weeks; the actual period would depend on the sediment source and incubation temperature. The validated systems were used with Rhine river sediment to assess possible effects on ecosystem parameters of Pseudomonas sp. strain B13 FR1(pFRC20P), a genetically engineered microorganism (GEM) that had been constructed to degrade mixtures of halo- and alkylbenzoates and -phenols. The GEM survived in the surface sediment at densities of 5 x 10(4) to 5 x 10(5)/g (dry weight) for 4 weeks and degraded added chloro- and methylaromatics. The GEM did not measurably influence ecosystem parameters such as photosynthesis, densities of selected heterotrophic bacteria, thymidine incorporation rate, and oxygen microgradients. Thus, the microcosm system described here would seem to be useful for the study of the ecology of biodegradation and the fate and effect of microorganisms introduced into the environment. PMID- 1599245 TI - Survival and function of a genetically engineered Pseudomonad in aquatic sediment microcosms. AB - Pseudomonas sp. strain B13 FR1(pFRC20P) is a genetically engineered microorganism (GEM) which is able to degrade chloro- and methylaromatics through a constructed ortho cleavage pathway. The fate of the GEM and its ability to degrade substituted aromatic compounds in two different aquatic sediments was investigated by using a microcosm system which consisted of intact layered sediment cores with an overlying water column. The GEM survived in Lake Plussee and in Rhine river sediments at densities of approximately 10(5) bacteria per g (dry weight) (1 to 5% of the total CFU) throughout a 4-week period of investigation. According to several criteria, the microcosm system was stable and healthy throughout the experiment and the addition of the GEM did not affect the total number of extractable CFU (I. Wagner-Dobler, R. Pipke, K. N. Timmis, and D. F. Dwyer, Appl. Environ. Microbiol. 58:1249-1258, 1992). When compared with uninoculated controls, the presence of the GEM enhanced the rate of degradation of a mixture of 3-chlorobenzoate and 4-methylbenzoate (25 microns each) which had been added to the water column of the sediment cores. PMID- 1599246 TI - Polymerase chain reaction and gene probe detection of the 2,4 dichlorophenoxyacetic acid degradation plasmid, pJP4. AB - Specific and sensitive detection of indigenous and introduced degradative organisms is an essential prerequisite to their use in remediation of toxic waste and soil systems. Procedures were employed for the use of polymerase chain reaction and gene probes for sensitive detection of the 2,4-dichlorophenoxyacetic acid-degrading bacterium, Alcaligenes eutrophus JMP134(pJP4). Two 20-mer oligonucleotide primers were identified for amplification of a 205-bp region of the tfdB gene of pJP4, and optimum conditions for amplification were determined. Both the polymerase chain reaction amplification process and hybridization with the 5'-end-labelled probe were found to be specific to organisms containing plasmid pJP4 or its derivative pRO103. Detection limits were determined for the template supplied either as bacterial cells or purified plasmid DNA. The detection was sensitive up to an initial inoculum of 3,000 CFU or 156 pg of total plasmid DNA. However, when the amplified product was transferred to a nylon membrane and hybridized with the 5'-end-labelled probe, the detection sensitivity increased to 300 CFU or 15.6 pg of plasmid DNA. This sensitive detection method is more specific than use of traditional indicator media (M. A. Loos, Can. J. Microbiol. 21:104-107, 1975). An oligonucleotide (20 bases) complementary to a sequence internal to the 205-bp region was synthesized and utilized as a probe to confirm the specificity of the detection. PMID- 1599247 TI - Isolation of Pseudomonas pickettii strains that degrade 2,4,6-trichlorophenol and their dechlorination of chlorophenols. AB - Three strains of Pseudomonas pickettii that can grow with 2,4,6-trichlorophenol (2,4,6-TCP) as the sole source of carbon and energy were isolated from different mixed cultures of soil bacterial populations that had been acclimatized to 2,4,6 TCP. These strains released 3 mol of chloride ion from 1 mol of 2,4,6-TCP during the complete degradation of the TCP. Of these strains, P. pickettii DTP0602 in high-cell-density suspension cultures dechlorinated various chlorophenols (CPs). Cells that were preincubated with 2,4,6-TCP converted isomers of 4-CP to the corresponding chloro-p-hydroquinones, but those preincubated with 4-CP converted CPs lacking a chlorine atom(s) at the o position to isomers of chlorocatechol. The ability of DTP0602 to dechlorinate 2,4,6-TCP was induced by 2,6 dichlorophenol, 2,3,6- and 2,4,6-TCP, and 2,3,4,6-tetrachlorophenol and was repressed in the presence of succinate or glucose. PMID- 1599249 TI - Complete oxidation of linear alkylbenzene sulfonate by bacterial communities selected from coastal seawater. AB - Anionic surfactants, especially alkylbenzene sulfonates, are discharged into marine areas in great quantities. Because of their poor biodegradability, linear alkylbenzene sulfonates accumulate in seawater and sediments. Bacterial communities that can degrade surfactants were selected from coastal seawater contaminated by urban sewage. All the isolated strains consisted of gram negative, strictly aerobic rods or helical bacteria. Some of these, though isolated from coastal seawater, did not need sodium for growth and appeared to be related to the genera Alcaligenes and Pseudomonas. Complete surfactant biodegradation was achieved by three important steps: terminal oxidation of the alkyl chain, desulfonation, and aromatic-ring cleavage. Only a few strains were able to carry out the first two steps. The aromatic ring was then cleaved by other strains that possess very specific enzymatic activities. Finally, a number of strains grew on short acids that were end-of-metabolism products of the others. PMID- 1599248 TI - Isolation and screening of plasmids from the epilithon which mobilize recombinant plasmid pD10. AB - This study examined the potential of bacteria from river epilithon to mobilize a recombinant catabolic plasmid, pD10, encoding 3-chlorobenzoate degradation and kanamycin resistance. Fifty-four mobilizing plasmids were exogenously isolated by triparental matings between strains of Pseudomonas putida and epilithic bacteria from the River Taff (South Wales, United Kingdom). Frequencies for mobilization ranged from 1.7 x 10(-8) to 4.5 x 10(-3) per recipient at 20 degrees C. The sizes of the mobilizing plasmids isolated ranged from 40 kb to over 200 kb, and 19 of 54 were found to encode mercury resistance. Plasmid-encoded resistance to tetracycline and streptomycin was also found but not resistance to UV light or various heavy metals. Eight plasmids of epilithic bacteria, analyzed by comparing restriction fragmentation patterns, showed significant differences between those isolated from different independent matings. Optimal temperatures for mobilization of pD10 were between 15 and 25 degrees C. Four mercury resistance plasmids were found to be broad host range, transferring mercury resistance and mobilizing pD10 readily to representative species of beta- and gamma-purple bacteria. In general, frequencies of pD10 mobilization by plasmids of epilithic bacteria were 2 to 3 orders of magnitude lower than conjugal transfer frequencies. Thus, there is a high potential for exchange of recombinant genes introduced into the epilithon by mobilization between a variety of bacterial species. PMID- 1599251 TI - Physicochemical and structural investigation of the surfaces of some anaerobic subgingival bacteria. AB - The surfaces of nine clinical isolates of Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, and Peptostreptococcus micros and that of laboratory strain P. gingivalis W83 were studied by using contact angle measurements, X-ray photoelectron spectroscopy, infrared spectroscopy, microelectrophoresis of whole cells, and transmission electron microscopy of whole and sectioned cells. P. intermedia strains were hydrophilic, as judged from their small water contact angles, and had highly negative zeta potentials, consistent with the presence of a prominent ruthenium red (RR)-staining layer and fibrillar appendages which are probably partly carbohydrate. The two clinical isolates of P. gingivalis were also hydrophilic and highly negatively charged despite the presence of prominent fibrils, which usually yield less negative zeta potentials. This finding suggests that the RR-staining layer dominates the suspension characteristics of P. gingivalis and P. intermedia strains. P. gingivalis W83 had no demonstrable fibrils and a morphologically distinct RR staining layer, and it was more hydrophobic than the two clinical isolates of P. gingivalis. P. micros isolates were hydrophobic and much less negatively charged than the other species. The A. actinomycetemcomitans strains displayed long, prominent fibrils and a very thin RR-staining layer, which resulted in high hydrophobicity but distinctly different zeta potentials for the two. Physicochemical data on microbial cell surfaces usually have clear and predictable relationships with each other. For the strains in this study that did not follow these relationships, their aberrant behavior could be explained as due to a masking effect caused by specific surface architecture. We conclude that this combined analysis provides a detailed image of subgingival bacterial surface architecture. PMID- 1599250 TI - Evidence for natural transfer of a tetracycline resistance gene between bacteria from the human colon and bacteria from the bovine rumen. AB - Previously, we demonstrated conjugal transfer of a specially constructed shuttle vector, pRDB5, from the human colonic anaerobe Bacteroides uniformis to the ruminal anaerobe Prevotella (Bacteroides) ruminicola B(1)4. We have now shown that naturally occurring gene transfer elements in Bacteroides species and Prevotella ruminicola can also be transferred between these two genera. A self transmissible chromosomal element originally found in a clinical isolate of Bacteroides fragilis (Tcr Emr 12256) was transferred from B. uniformis 0061 to P. ruminicola B(1)4 and from P. ruminicola B(1)4 back to B. uniformis or to another human colonic species, Bacteroides thetaiotaomicron. Similarly, a conjugative plasmid (pRRI4) originally found in P. ruminicola 223 was transferred from P. ruminicola B(1)4 to B. uniformis or B. thetaiotaomicron. pRRI4 could be transferred from the colonic Bacteroides species only if the donor strain contained the Tcr Emr 12256 element in its chromosome. These results show that transfer of naturally occurring elements can be demonstrated under laboratory conditions. Evidence that such transfers may actually have occurred in nature came from our finding that the tetracycline resistance (Tcr) gene on the P. ruminicola plasmid pRRI4 hybridized on high-stringency Southern blots with the Tcr gene found on the Bacteroides Tcr elements. The presence of the same gene in such distantly related genera of bacteria is most likely to have occurred as a result of horizontal transfer. PMID- 1599253 TI - Evidence for an NIH shift in oxidation of naphthalene by the marine cyanobacterium Oscillatoria sp. strain JCM. AB - The marine cyanobacterium Oscillatoria sp. strain JCM oxidized naphthalene predominantly to 1-naphthol. Experiments with [1-2H]naphthalene and [2 2H]naphthalene indicated that 1-naphthol was formed with 68 and 74% retention of deuterium, respectively. No significant isotope effect was observed when the organism was incubated with a 1:1 mixture of naphthalene and [2H8]naphthalene. The results indicate that 1-naphthol is formed through a naphthalene 1,2-oxide intermediate, which rearranges spontaneously via an NIH shift mechanism. PMID- 1599254 TI - Reductive dehalogenation of chlorophenols by Desulfomonile tiedjei DCB-1. AB - Reductive dehalogenation of chlorophenols has been reported in undefined anaerobic cultures but never before in an anaerobic pure culture. We found that the sulfate-reducing bacterium Desulfomonile tiedjei DCB-1 reductively dehalogenates pentachlorophenol (PCP) and other chlorophenols. The maximum rate of PCP dechlorination observed was 54 mu mol of Cl- h-1 g of protein-1. 3 Chlorobenzoate appeared to serve as a required inducer for PCP dehalogenation; however, neither PCP nor 3-chlorophenol induced dehalogenation. Dehalogenation was catalyzed by living cells, and formate served as a required electron donor. D. tiedjei dehalogenated meta-chlorine substituents of chlorophenols (i.e., PCP was degraded to 2,4,6-trichlorophenol). Generally, more highly chlorinated phenol congeners were more readily dechlorinated, and 3-chlorophenol was not dehalogenated. Growing cultures dehalogenated PCP, but greater than 10 microM PCP (approximately 1.7 mmol g of protein-1) reversibly inhibited growth. PMID- 1599255 TI - Survival and replication of male-specific bacteriophages in molluscan shellfish. AB - The survival and replication of male-specific bacteriophages in hard-shelled clams (Mercenaria mercenaria) and their homogenates were examined to further assess their potential utility as indicator organisms. Trials were conducted in the presence and absence of a suitable bacterial host, Escherichia coli HS[pFamp]R. Results of this study demonstrated that male-specific bacteriophages were unable to replicate in hard-shelled clams, with or without added host cells. In addition, the densities of these bacteriophages were stable for up to 7 days in shellfish held at ambient seawater temperatures (less than 25 degrees C). Evidence of replication, although not observed in live shellfish, was found to occur in temperature-abused shellfish homogenates and supernatants, but only when a suitable bacterial host was present. PMID- 1599252 TI - Metabolism of phenanthrene by the marine cyanobacterium Agmenellum quadruplicatum PR-6. AB - Under photoautotrophic growth conditions, the marine cyanobacterium Agmenellum quadruplicatum PR-6 metabolized phenanthrene to form trans-9,10-dihydroxy-9,10 dihydrophenanthrene (phenanthrene trans-9,10-dihydrodiol) and 1 methoxyphenanthrene as the major ethyl acetate-extractable metabolites. Small amounts of phenanthrols were also formed. The metabolites were purified by high pressure liquid chromatography and identified from their UV, infrared, mass, and proton magnetic resonance spectral properties. A. quadruplicatum PR-6 formed phenanthrene trans-9,10-dihydrodiol with a 22% enantiomeric excess of the (-) 9S,10S-enantiomer. Incorporation experiments with 18O2 showed that one atom of oxygen from O2 was incorporated into the dihydrodiol. Toxicity studies, using an algal lawn bioassay, indicated that 9-phenanthrol and 9,10-phenanthrenequinone inhibit the growth of A. quadruplicatum PR-6. PMID- 1599256 TI - Conditions for protoplasting, regenerating, and transforming the calicheamicin producer, Micromonospora echinospora. AB - We report methods to generate protoplasts, to regenerate mycelia, and to transform Micromonospora echinospora. This actinomycete produces the unusual antitumor antibiotics, the calicheamicins. These protocols may be applied to other actinomycetes that have been difficult to transform. These methods also may facilitate the cloning of calicheamicin biosynthetic genes by genetic complementation. PMID- 1599258 TI - Efficient fermentation of Pinus sp. acid hydrolysates by an ethanologenic strain of Escherichia coli. AB - Process conditions for the acid hydrolysis of pine hemicellulose and cellulose have been described which provide a biocompatible sugar solution. By using an improved strain of recombinant Escherichia coli, strain KO11, hydrolysates supplemented with yeast extract and tryptone nutrients were converted to ethanol with an efficiency of 85% to over 100% on the basis of monomer sugar content (approximately 72 g/liter) and with the production of 35 g of ethanol per liter in 48 h. In the process described, approximately 347 liters of ethanol could be produced per dry metric ton of lignocellulose. PMID- 1599257 TI - Method to identify specific alleles of a Phanerochaete chrysosporium gene encoding lignin peroxidase. AB - A method to identify and differentiate allelic variants of the gene encoding lignin peroxidase isozyme H8 is presented. The strategy involves amplifying a variable region of the gene's carboxy terminus by use of the polymerase chain reaction and then probing with allele-specific oligonucleotides. PMID- 1599259 TI - Use of a genetically engineered Escherichia coli strain to produce 1,2-dihydroxy 4'-chlorobiphenyl. AB - Genetically engineered kanamycin-resistant Escherichia coli HB101 containing the mutant chimeric plasmid pAW6194-T17 specifying biphenyl dioxygenase and dihydrodiol dehydrogenase and lacking the ability to produce active 3 phenylcatechol dioxygenase was used to produce 1,2-dihydroxy-4'-chlorobiphenyl (DHCB) from 4-chlorobiphenyl. Resting-cell suspensions of genetically engineered E. coli in mineral salts medium (pH 7.0) containing 880 microM 4-chlorobiphenyl produced 110 microM DHCB. The Km for 4-chlorobiphenyl was 3.3 mM. Biotransformation of DHCB from 4-chlorobiphenyl was maximum when cells (2.5 mg of protein per ml) were incubated with shaking (150 rpm) at pH 7.0 and 30 degrees C for 6 h. The enzymatically produced DHCB was a suitable substrate for assaying 3 phenylcatechol dioxygenase activity. Biologically produced DHCB showed UV and mass spectra similar to those of chemically synthesized DHCB. The bioconversion rate of ortho-substituted chlorobiphenyl was slower than that of the para- or meta-substituted chlorobiphenyl. PMID- 1599260 TI - Cloning, expression, and nucleotide sequence of a lipase gene from Pseudomonas fluorescens B52. AB - In this study, we report the cloning and expression of lipase gene from Pseudomonas fluorescens B52, a psychrotrophic spoilage bacterium isolated from refrigerated raw milk. Sequence analysis revealed one major open reading frame of 1,428 nucleotides that was predicted to encode a protein with a molecular weight of 50,241. The predicted enzyme was found to contain an amino acid sequence highly homologous to the putative substrate-binding domain present within all lipases examined to date. PMID- 1599261 TI - Sporulation and enterotoxin production by Clostridium perfringens type A at 37 and 43 degrees C. AB - Enterotoxin-positive strains of Clostridium perfringens were grown in Duncan Strong sporulation medium in the presence of 0.4% (7.9 mM) raffinose at 37 and 43 degrees C. Enterotoxin- and heat-resistant spores were produced at similar concentrations but sooner at 43 degrees C than at 37 degrees C. There was a direct relationship between spore heat resistance and sporulation temperature (32, 37, and 43 degrees C). PMID- 1599262 TI - Cutaneous leishmaniasis treated with controlled localized heating. PMID- 1599263 TI - Skin manifestations of mustard gas. A clinical study of 535 patients exposed to mustard gas. AB - BACKGROUND: During the Iraq-Iran war (1980-1988), 535 patients who were exposed to mustard gas (one of the chemical warfare agents used by Iraq) were referred to our dermatology department. In this article, we have tried to review the skin manifestations of these patients. OBSERVATIONS: The skin lesions were of early or late onset. The early onset lesions consisted of erythema (76%), bulla (55%), and purpura (1.1%). These lesions were mostly found on the face and skin folds. The late-onset manifestations were pigmentation (20.4%) and desquamation (11.2%). Other complications were ophthalmic (85%), pulmonary (15%), and gastrointestinal (10%). Lymphopenia (7%) was the most serious laboratory disorder reported. Biopsy specimens of the lesions showed subepidermal bullae with mild dermal and epidermal necrosis. CONCLUSIONS: All patients were treated as for burns using sulfadiazine and furacine. All patients were cured in a period of 15 to 45 days. During a 6-month follow-up, no mortality was observed. PMID- 1599264 TI - Intralesional cyclosporine for psoriasis. Relationship of dose, tissue levels, and efficacy. AB - BACKGROUND AND DESIGN--To avoid systemic side effects, topical and intralesional administration of cyclosporine has been used; however, only intralesional administration has been successful. To understand more about the dosing requirements and resultant tissue levels of intralesional cyclosporine, we injected psoriasis plaques in a double-blind fashion with three different concentrations of cyclosporine (17 mg/mL in seven patients, 10 mg/mL in 13 patients, and 2.5 mg/mL in 11 patients) or matching vehicle three times weekly for 4 weeks. RESULTS--Statistically significant improvement was observed in plaques treated with 17 mg/mL (P = .003) compared with vehicle-treated plaques; the improvements in plaques treated with 10 mg/mL (P = .078) and 2.5 mg/mL (P = .054) achieved marginal statistical significance compared with vehicle treatment. Four weeks after discontinuation of therapy, the change from pretherapy in plaques that had received 17 mg/mL of cyclosporine was statistically significantly better (P less than .0001) than that with vehicle treatment. A similar finding but of marginal statistical significance (P = .059) occurred in the plaques that had received 10 mg/mL of cyclosporine. Throughout the study, untreated psoriasis plaques did not improve. Transient pain was the most common side effect noted with both cyclosporine and vehicle injections. Tissue levels of cyclosporine tended to be highest in plaques receiving the 17-mg/mL concentration; blood levels of cyclosporine were low throughout the study. CONCLUSIONS: --Intralesional cyclosporine requires a sufficient dosage to improve psoriasis, apparently by a local mechanism of action. Improvement may persist for 4 weeks or longer. PMID- 1599265 TI - Circulating activated T lymphocytes in autoeczematization. AB - BACKGROUND AND DESIGN: Autoeczematization, the symmetric diffuse spread of a previously localized dermatitis, has an unclear etiology although some investigators have postulated that activated T lymphocytes play a role. Two estimates of activation of peripheral T lymphocytes are the cell surface expression of the HLA-DR antigen and the interleukin 2 receptor (IL-2R). We measured the percentage of circulating activated T lymphocytes in nine patients with autoeczematization compared with normal controls (n = 10), patients with stasis dermatitis (n = 6), and patients with severe (n = 10) or mild (n = 8) psoriasis. The percentage of activated T lymphocytes was determined by fluorescent, activated cell sorter analysis of peripheral leukocytes doubly stained with antibodies to T lymphocytes and HLA-DR antigen or IL-2R. RESULTS: Statistically significant elevations of HLA-DR- and IL-2R--positive T lymphocytes were seen in autoeczematization patients (P less than .004 and P less than .04, respectively) and those with severe psoriasis (P less than .004 for HLA-DR antigen and IL-2R). Percentages of HLA-DR- and IL-2R--positive T lymphocytes in patients with mild psoriasis were not significantly elevated. Two patients with autoeczematization had a reduction of their previously elevated levels of HLA-DR- and IL-2R--positive T lymphocytes after treatment. CONCLUSIONS: These data suggest a possible role for circulating activated T lymphocytes in the pathogenesis of autoeczematization and possibly in severe psoriasis. PMID- 1599266 TI - Immunologic abnormalities associated with primary anetoderma. AB - BACKGROUND AND DESIGN: Primary anetoderma is a rare cutaneous elastolytic disorder, the etiopathogenesis of which has not yet been established. Six patients with primary anetoderma were studied in an attempt to assess the role of the immunologic system in the elastolytic process. The investigation included the medical history, physical examination, routine blood tests, specific tests for collagen diseases, prothrombin time, activated partial thromboplastin time, thyroxine, indirect immunofluorescence test, and skin biopsies for histopathologic study and direct immunofluorescence. RESULTS: Two of the patients presented with autoimmune disorders: the first had Graves' disease, lupus anticoagulant, and autoimmune hemolysis, and the second had systemic scleroderma. There were positive direct immunofluorescence findings in most of the patients. Furthermore, all of them were found to have serologic immunologic abnormalities, of which the most common was a positive antinuclear factor. CONCLUSIONS: These findings indicate that there is an immunologic involvement in primary anetoderma. PMID- 1599267 TI - Localized vulvar pemphigoid in a child misdiagnosed as sexual abuse. AB - BACKGROUND: Various primary dermatoses can affect the vulva of children and be misdiagnosed as child abuse, with devastating social consequences. OBSERVATION: A 3-year-old girl with vulvar erosions was removed from her parent's care after a pediatrician and gynecologist diagnosed child abuse. Histopathologic and immunofluorescence studies were consistent with vulvar pemphigoid. CONCLUSION: Localized pemphigoid should be added to the differential diagnosis of vulvar lesions. Dermatologists, pediatricians, and gynecologists should be familiar with nonvenereal diseases that can exclusively affect this area. The dermatologist's expertise is particularly valuable in differentiating between primary diseases and sexual abuse. PMID- 1599269 TI - Reiter's syndrome of the vulva. The psoriasis spectrum. AB - BACKGROUND: Reiter's syndrome is a disease characterized by crusted, scaling, acral and genital plaques; urethritis or cervicitis; and arthritis, which occur in genetically susceptible patients in response to any of many infections. This disease rarely occurs in women, and specific characterizations of vulvar and cervical lesions are rare. OBSERVATIONS: We describe a 39-year-old woman with a history of mucocutaneous candidiasis that was refractory to oral ketoconazole therapy. She presented with well-demarcated, erythematous, crusted plaques over the vulva, hands, and feet, as well as with cervical lesions and a history of conjunctivitis and iritis. Following the biopsy of characteristic skin lesions, recognition of systemic signs, and cultures that were negative for yeast, her condition was diagnosed as Reiter's syndrome. CONCLUSIONS: Reiter's syndrome of the vulva, vagina, and cervix may not be recognized because of its uncommon occurrence in women and the physician's consequent unfamiliarity with its clinical appearance in the genital area. This disease and pustular psoriasis share many common features and exist on a spectrum. A high index of suspicion and correlation of the many facets of the disease will better enable the clinician to make this diagnosis. PMID- 1599268 TI - Childhood localized vulvar pemphigoid is a true variant of bullous pemphigoid. AB - BACKGROUND: Childhood localized vulvar pemphigoid has been recently reported in four girls. A fifth child with this proposed rare variant of bullous pemphigoid is described. Moreover, findings in the various immunopathologic studies we performed establish this entity as a true morphologic variant of bullous pemphigoid. OBSERVATIONS: In situ deposits of IgG in this patient's epidermal basement membrane zone localized to the epidermal side of 1 mol/L of saline-split skin. Moreover, the patient had circulating IgG autoantibodies that bound the epidermal side of 1 mol/L of saline-split skin in indirect immunofluorescence microscopy and immunoprecipitated the 230-kd bullous pemphigoid antigen from biosynthetically radiolabeled human keratinocyte extracts. These laboratory findings are identical to those documented in patients with the generalized "classic" form of bullous pemphigoid. CONCLUSIONS: This study demonstrates that a child with clinical, histopathologic, and immunopathologic features of localized vulvar pemphigoid had circulating autoantibodies that identify a specific keratinocyte antigen, the bullous pemphigoid antigen, which may serve as a molecular marker for this disease. PMID- 1599270 TI - The oral mucosal punch biopsy. A report of 140 cases. AB - BACKGROUND: Dermatologists are often confronted with neoplasms and diseases of the oral cavity. Although many may be reluctant to perform oral surgical procedures, a biopsy is often needed to establish a definitive diagnosis. This article describes a simple and safe method of obtaining an oral biopsy specimen. OBSERVATIONS: A punch was used in performing 140 biopsies from various locations of the oral cavity. Bleeding was controlled by pressure in the majority of cases, with only a few requiring electrodesiccation. Biopsy sites, all of which were left to heal by secondary intention, showed almost complete reepithelialization at a 2-week postoperative check. Complications from surgery were almost nonexistent and minor in degree. CONCLUSIONS: The punch biopsy of the oral cavity is a safe and useful technique that can be easily employed by dermatologists. Biopsies should be kept superficial, and neurovascular structures must be avoided to prevent complications. PMID- 1599271 TI - Somatostatin analogue scintigraphy. A simple and sensitive method for the in vivo visualization of Merkel cell tumors and their metastases. AB - BACKGROUND: Trabecular carcinomas of the skin, or Merkel cell tumors, are aggressive neoplasms that tend to occur in sun-exposed skin. These tumors frequently metastasize and, despite therapy, the number of disease-related deaths is high. Ultrastructurally and immunocytochemically, the majority of these tumors have neuroendocrine characteristics. Recently, we described the in vivo visualization of various neuroendocrine tumors after injection of a radiolabeled somatostatin analogue (octreotide). In this study, we report the results of scintigraphy with radioactive-labeled somatostatin analogues in five patients with Merkel cell tumors. OBSERVATIONS: In all four patients in whom tumor was detected using computed tomographic scanning and ultrasound, the tumor sites were also demonstrated on octreotide scintigrams. In one patient, a tumor with a diameter that was smaller than 0.5 cm could not be detected with octreotide scintigraphy, computed tomography, or ultrasound. Using octreotide scintigraphy we found presumed tumor spots in two patients that were not evident when other techniques were used. CONCLUSIONS: Octreotide scintigraphy has an equal or even greater sensitivity than computed tomography and ultrasound for detecting Merkel cell tumors and their metastases. Establishing the spread of the disease in this way may ensure an optimal choice of treatment in patients with this type of tumor. PMID- 1599272 TI - Suction purpura. AB - BACKGROUND: Purpuric eruptions due to local mechanical causes are commonly seen, particularly in children. These eruptions are not always recognized as isolated purpura, and the patient may be submitted to an unnecessary extensive hematologic workup. We present various causes of suction purpura and outline a logical investigational approach. OBSERVATIONS: Suction purpura result from an external force exerting negative pressure on a circumscribed area of the skin, producing small grouped petechiae. We present a number of such suction purpura-causing mechanisms: Pressure during the delivery of a neonate, children's habits or play activities, and iatrogenic causes produce similar cutaneous lesions. We also describe the gas mask suction purpura for the first time. CONCLUSIONS: Once the causative factor is established, there is no need for further investigation or treatment of suction purpura. The lesions will fade completely within a few days. PMID- 1599273 TI - Estrogen receptors and the response to sex hormones in angiolymphoid hyperplasia with eosinophilia. AB - BACKGROUND: Angiolymphoid hyperplasia (ALH) with eosinophilia is a benign rare tumor, characterized by marked proliferation of endothelial cells. The tumors are associated with extensive infiltrate of lymphocytes, histiocytes, and eosinophils, and occur on the head and neck of young adults. A variety of treatments have been attempted with frequent recurrences. We report two cases of ALH with eosinophilia that seemed to be dependent on sex hormones. OBSERVATION: The first case is a patient with ALH that resolved after stopping treatment with birth control pills. Biopsy specimens of the tumor demonstrated increased level of estrogen and progesterone receptors compared with her normal skin. The second case is a patient with a previous lesion of ALH with eosinophilia, who during pregnancy had new lesions develop and whose primary lesion increased in size. All lesions decreased to half their original sizes after pregnancy. CONCLUSION: Both of these cases suggest a role for hyperestrogen states with the presence of hormonal receptors. The response to sex hormones could contribute to the pathogenesis of the disease and may offer future alternative treatment modalities. PMID- 1599274 TI - The cutaneous manifestations of violence and poverty. AB - BACKGROUND: Violence is a public health issue that disproportionately affects the poor. Homelessness, drug abuse, and physical violence are seen with increasing frequency in poor communities. This article reviews the cutaneous manifestations of violence and the dermatologic problems commonly seen in the homeless. Particular emphasis is placed on the experience of municipal hospitals serving the urban poor. OBSERVATIONS: Dermatologic diseases are common in the homeless, and foot-related problems such as cellulitis and pyodermas are frequent causes of hospitalization. Unusual patterns of scarring and bruises in different stages of healing are seen in victims of physical violence. Trauma and sexually transmitted diseases result from sexual abuse. Serious skin infection and self-mutilating scarring are seen in intravenous drug abusers. CONCLUSION: Dermatologists are able to diagnose and treat the many skin problems seen in the poor and to identify the physical manifestations of abuse during routine skin examination. Findings of violence should be documented and reported to the appropriate investigational agencies. PMID- 1599275 TI - Dermatology in Singapore at the crossroads. PMID- 1599276 TI - Family violence, child abuse, and anogenital warts. PMID- 1599277 TI - Diagnosing child abuse. The cost of getting it wrong. PMID- 1599278 TI - Painful nodules in a young female. Antiphospholipid syndrome. PMID- 1599279 TI - Unusual digital nodules. Multicentric reticulohistiocytosis (MRH). PMID- 1599280 TI - Persistent nodule on the toe following trauma. Sporotrichoid Mycobacterium marinum infection. PMID- 1599281 TI - Painful solitary subungual nodule. Subungual exostosis (SE). PMID- 1599282 TI - The effect of flash lamp-pulsed dye laser on psoriasis. PMID- 1599283 TI - Association of granuloma annulare with sarcoidosis. PMID- 1599284 TI - Fine-needle aspiration biopsy, curettage, and swab samples in bacteriologic analysis of leg ulcers. PMID- 1599285 TI - Discrete papular mucinosis responding to intralesional and topical steroids. PMID- 1599286 TI - Acrodermatitis chronica atrophicans. PMID- 1599287 TI - Eruptive spider nevus-like lesions associated with the hyperviscosity syndrome. PMID- 1599289 TI - 'Personal child health records' held by parents. PMID- 1599288 TI - Diabetes in puberty. PMID- 1599290 TI - Medulloblastoma. PMID- 1599291 TI - Profile of bronchial responsiveness in children with respiratory symptoms. AB - A postal questionnaire inquiring into the presence of respiratory symptoms was sent to 3698 children aged 7 and 8 years. Those reporting either cough or wheeze were randomised, and a sample invited to attend for skin testing. A total of 192 symptomatic children, half of whom were atopic and half non-atopic, were randomly selected to enter the study. All children performed and recorded best of three peak expiratory flow measurements twice a day and completed a 10 point respiratory symptom score card each day for one year. They also recorded all treatment taken and made a note of relevant life events. Each child was seen monthly for general assessment and for measurement of nonspecific bronchial responsiveness to methacholine. Of the 192 children, 183 successfully completed the study. For six subjects 11 measurements of the provocation dose required to cause a 20% fall in forced expiratory volume in one second (PD20) were available for analysis and on the remaining 177, greater than or equal to 12 measurements. The prevalence and degree of bronchial hyper-responsiveness (PD20 less than 6.4 mumol) and its relationship to atopy was examined by comparing the percentage of members of each symptom group demonstrating bronchial hyper-responsiveness and the number of occasions on which they did so, and by comparison of minimum and median PD20 values. The range of bronchial responsiveness shown during the study period by each child was expressed as doubling doses of methacholine and compared between symptom groups. Atopy and wheeze were both independently associated with an increased prevalence and greater degree of bronchial hyper-responsiveness when compared with non-atopy and cough respectively, all differences being significant a the 0.001 level.. Thirty three per cent of subjects demonstrated a rnge of methacholine responsiveness of >4 and 13.4% of >6 doubling doses during one year. PMID- 1599292 TI - Drug delivery from holding chambers with attached facemask. AB - There is much interest in the use of holding chambers with an attached facemask to deliver aerosols from metered dose inhalers to infants. In order to study the influence of various design factors on the dose inhaled at different tidal volumes, a model was constructed in which a Starling ventilator was used to generate an inspiratory/expiratory cycle across a filter. Sodium cromoglycate was administered via a Nebuhaler and mask, Aerochamber and mask, and a coffee cup using tidal volumes of 25, 50, and 150 ml and the dose deposited upon the filter after six breaths was assayed using an ultraviolet spectrophotometric method. At the lowest tidal volume the high aerosol concentration in the smaller chamber enhanced drug delivery while at the highest tidal volume delivery was greatest from the larger chamber reflecting the larger dose available. Multiple breaths ensured that the dose inhaled per kilogram from each chamber was relatively large and also permitted significant drug delivery despite the introduction of a relatively large dead space between valve and filter. The dose delivered was increased by increasing the dose introduced into the chamber though not proportionately. These devices appear likely to deliver significant quantities of aerosol to infants, though drug delivery may be enhanced by the use of an appropriate valve. PMID- 1599293 TI - Drug delivery from jet nebulisers. AB - Maximising the rate of drug delivered in particles small enough to reach the lower respiratory tract from jet nebulisers may allow treatment times to be reduced and thus improve the acceptability of this form of treatment, particularly in very young patients. The role of various technical factors such as driving gas flow (DGF) in determining the rate of drug delivery was studied by constructing a model to simulate the respiratory pattern of individuals with different tidal volumes using a Starling ventilator and filter. Sodium cromoglycate was nebulised under a variety of operating conditions and the dose deposited on the filter was assayed. Tidal volumes of 50 and 400 ml were used at a frequency of 32 breaths per minute. Increasing the DGF from 4 to 8 l/minute produced a 264% increase in the rate of drug output but only a 32% increase in aerosol concentration. The mass of drug contained within droplets less than 5 microns increased from 26.8% to 70.8% of the total. The resultant increase in rate of drug delivery to the filter was 34% for a tidal volume of 50 ml and 79% for a tidal volume of 400 ml though the dose contained within droplets less than 5 microns increased by 4-fold at 50 ml tidal volume and by more than 5-fold at the higher tidal volume. Halving the solution concentration halved the rate of drug delivery. Increasing the tidal volume 8-fold from 50 to 400 ml resulted in an increase in the rate of drug deposition upon the filter of only 2.2 to 3-fold depending upon the DGF so that substantially more drug per ml inhaled was delivered at the lower tidal volume. These results are explained by considering factors that influence the rate of drug delivery. At low tidal volumes the rate of drug delivery at a given respiratory rate is dependent on the tidal volume and aerosol concentration. At high tidal volumes it is dependent upon aerosol concentration and volume of available aerosol and is essentially independent of tidal volume. PMID- 1599294 TI - Role of infection in the middle lobe syndrome in asthma. AB - Twenty one children with asthma aged 1.0-10.5 years (mean (SD) 3.3 (2.5) years) were admitted to the hospital to evaluate pulmonary right middle lobe or lingular collapse lasting one to 12 months (mean (SD) 4.4 (3.8) months). Seven children had mild asthma and were treated with inhaled beta 2 agonists as needed. Nine had moderate asthma treated with either sodium cromoglycate or slow release theophylline. Five had severe asthma treated with inhaled steroids. Each child underwent fibreoptic bronchoscopy under local anaesthesia and a bronchoalveolar lavage. Differential cell counts of the lavage fluid revealed predominance of neutrophils in 12 patients (57%). In nine of these patients cultures grew pathogenic bacteria, mainly Haemophilus influenzae and Streptococcus pneumoniae. There was no correlation between the severity of asthma and a positive bacterial culture. There was also no correlation between the duration of the right middle lobe collapse and a positive culture. We conclude that longstanding right middle lobe collapse in asthmatic children is often associated with bacterial infection. PMID- 1599295 TI - HIV-1 infection and perinatal mortality in Zimbabwe. AB - As part of a survey of the causes of perinatal mortality at Mpilo Maternity Hospital, 220 neonatal deaths and the mothers of 221 stillbirths were tested for HIV-1 antibodies. The HIV positive rate in neonatal deaths was 23.6% (95% confidence interval (CI) 18.0 to 29.2%), significantly higher than 15.4% (95% CI 10.6 to 20.1%) in stillbirths. Perinatal deaths from congenital malformations, birth asphyxia, pregnancy induced hypertension, placental abruption, and oFther non-infectious causes had similar low HIV positive rates averaging 8.1% (95% CI 3.9 to 12.3%). Deaths from septicaemia had a significantly greater rate of 39.3% (95% CI 27.0 to 51.6%) and the highest rate of 72.2% (95% CI 51.5 to 92.9%) was found in deaths from congenital infection other than syphilis, indicating that maternal HIV infection predisposes to neonatal septicaemia and congenital infection. Unexplained stillbirths also had a significantly greater rate of 22.4% (95% CI 10.7 to 34.1%), presumably because some died from unrecognised infection. The rate in deaths from congenital syphilis was 17.4% (95% CI 9.6 to 25.2%), indicating a significant but weak association between these two sexually transmitted diseases in Bulawayo. The rate in deaths from hyaline membrane disease was not significantly greater at 15.0% (95% CI 6.0 to 24.0%). By predisposing to infection, maternal HIV infection was estimated to increase the stillbirth rate by 1.6 times and the neonatal mortality rate by 2.7 times. It predisposed equally to early and late onset neonatal septicaemia, but more to infection from streptococci and staphylococci than from Gram negative enterobacteria. HIV positive deaths from congenital infection had respiratory distress and usually intrauterine growth retardation, hepatosplenomegaly, and congenital pneumonia on lung histology. PMID- 1599296 TI - Deaths at home and in hospital in Zimbabwe. AB - A prospective study was done of children less than 13 years of age, who died at home or on their way to hospital and those who died in hospital, over a one year period. Fifty seven (86%) of the 66 children who were dead on arrival and 94 (77%) of the 122 children who died after admission were 2 years old or less. The main causes of death in both groups were identical and infections were the most frequent diagnosis. AIDS was the most common cause with 23 (35%) of the deaths in the children who were dead on arrival and 27 (22%) of the deaths in the children who died after admission. An overall positive HIV-I serology was found in 31 (47%) of the children in the dead on arrival group and in 50 (41%) of the children in the group that died after admission. PMID- 1599297 TI - Intensive enteral feeding in advanced cirrhosis: reversal of malnutrition without precipitation of hepatic encephalopathy. AB - Ten children with advanced cirrhosis and malnutrition (less than 90% weight for height) were fed for eight weeks with a nasogastric feed comprising whey protein (enriched with branched chain amino acids), fat as 34% medium chain and 66% long chain triglycerides, and glucose polymer. Six of the children were studied for an eight week control period before feeding. Weight, triceps skinfold thickness, mid arm circumference, mid-arm muscle area, and fasting plasma ammonia and amino acid concentrations were measured before and after the control period and after the consequent feed period. Results showed that despite high energy and protein intakes the children remained malnourished over the control period. All anthropometric indices improved significantly during the feed period, and no child developed clinical encephalopathy. The feed period was associated with a small, and not clinically significant, increase in the plasma ammonia concentration, but no consistent trend in the plasma amino acid concentrations. Thus, in children with advanced hepatobiliary disease awaiting liver transplantation, enteral feeding improved nutritional status without adverse clinical or biochemical effects. PMID- 1599298 TI - Using the steatocrit to determine optimal fat content in modular feeds. AB - The steatocrit was measured in infants with protracted diarrhoea who were receiving intragastric modular feeds. Measurements were made when fat intake was constant to determine steatocrit variability and during increases in fat intake to determine fat tolerance limits. Steatocrit variability was expressed as the range between a subject's lowest and highest steatocrit value. The median between stool and between-day variabilities were 2% and 11% respectively. Variability was also measured in seven healthy breast fed infants. In the five still displaying appreciable physiological steatorrhoea, the between-day variability (median 8%) and between-stool variability (median 9%) were not significantly different from the protracted diarrhoea group. In the fat tolerance investigations in the protracted diarrhoea group, the steatocrit increased with increases in the module fat content. Fat intake and steatocrit were significantly positively related. A significant negative correlation was seen between steatocrit and weight gain, the latter becoming negligible at steatocrit values around 30%. PMID- 1599299 TI - Electrogastrography in non-ulcer dyspepsia. AB - Fasting and fed gastric electrical activity was recorded by cutaneous electrodes (electrogastrography) in 14 children with unexplained recurrent symptoms of upper intestinal dysfunction, and in 10 controls. The unexplained symptoms included vomiting, epigastric pain, fullness, and early satiety. Mean (SD) age was 7.0 (3) and 7.5 (2) years, respectively. Gastric emptying time of a solid-liquid meal was also measured by real time ultrasonography in all subjects (patients and controls). In all patients radiography and endoscopy excluded structural and focal abnormalities of the gastrointestinal tract. Gastric emptying time was significantly more prolonged in patients than in controls. It was also found that there were appreciable irregularities of gastric electrical rhythm (tachygastria, bradygastria, flat line pattern, and mixed arrhythmia) in 12 fasting and 10 fed patients, whereas controls showed short and rare episodes of arrhythmia during both fasting and fed recording periods. The percentage distribution of the total electrogastrographic energy power across three frequency bands of electrical activity (low, normal, and high) showed that patients were different from controls both for reduced activity of normal frequency and for increased incidence of high and low abnormal frequencies. It is concluded that gastric electrical abnormalities are found in a high proportion of children with recurrent unexplained upper gastrointestinal symptoms. Electrogastrography can be a valuable tool in the assessment of these patients. PMID- 1599301 TI - Should audio recordings of outpatient consultations be presented to patients? AB - Three hundred and four new and return paediatric outpatient consultations were tape recorded. Questionnaires (and tapes) relating to the experience were returned from 286 families. They showed that tapes had been helpful to more than 99% of parents and grandparents. The main benefits were in refreshing the memories of those who attended the consultation and in helping the understanding of those unable to attend. More than 70% of tapes were listened to more than once and a third of families made a copy. Most parents considered that all consultations should be taped. PMID- 1599300 TI - Gaviscon and Carobel compared with cisapride in gastro-oesophageal reflux. AB - We compared the efficacy of the prokinetic agent cisapride with that of Gaviscon (an alginate/alkaline compound) plus Carobel (carob seed flour) in the treatment of gastrooesophageal reflux (GOR). Fifty infants with confirmed GOR received either oral cisapride (0.8 mg/kg/day) or Gaviscon plus Carobel for one month in a randomised, parallel group study. Parental evaluations, diary scores, and 24 hour lower oesophageal pH recordings before and at the end of each treatment were compared. In the cisapride group 14/26 (53%) were considered better by their parents compared with 19/24 (79%) of those who received Gaviscon plus Carobel. Diary scores, range (0.00-1.00), improved in both groups with the median change being greater in the Gaviscon plus Carobel group (-0.21) than the cisapride group (-0.15). Five of 17 pH variables had significantly improved from baseline in infants who had received cisapride compared with 11/17 in those receiving Gaviscon plus Carobel. However, unpaired analysis of diary and pH data showed no significant differences between the two groups. We conclude that first line treatment of GOR with cisapride is no more effective than conventional treatment with Gaviscon plus Carobel. PMID- 1599302 TI - Chloroquine in idiopathic pulmonary haemosiderosis. PMID- 1599303 TI - Height and body proportions in child abuse. AB - Abused children are said to retain 'infantile body proportions'. The presenting height, sitting height, and leg length standard deviation scores of 91 victims have been calculated from data derived from a study of local inner city schoolchildren. In the study population 31/91 (34%) were significantly short and all but two of these had relatively shorter legs than backs, this limb disproportion being significant in 17. In 25 patients of the original group followed up after various social interventions there was a significant recovery of leg length. Measurement of height and proportionality, especially when compared with appropriate modern or local standards, is an important means of detecting and following up victims of child abuse. PMID- 1599304 TI - Home blood pressure monitoring in diabetes. AB - Forty three children with diabetes were recruited to evaluate home blood pressure monitoring using an electronic oscillometric sphygmomanometer (Philips HP5330). This device was found to be simple to use and reliable. It fulfilled the accuracy criteria of the American Association for the Advancement of Medical Instrumentation for both systolic and diastolic blood pressure and those of the British Hypertension Society for systolic blood pressure. Thirty eight children successfully measured their own blood pressure at home and taught other family members to do the same. The results indicate that home blood pressure monitoring is of value in the management of diabetic children. PMID- 1599306 TI - Treatment of refractory ulcerative oesophagitis with omeprazole. AB - A 7 year old boy with ulcerative oesophagitis failed to respond to a two month course of intensive medical treatment using H2 receptor antagonist treatment in combination with domperidone and sucralfate. He demonstrated complete resolution using omeprazole 10 mg once a day for eight weeks. PMID- 1599305 TI - Incidence of normal micturition in myelomeningocele patients. AB - Among 108 consecutive patients with myelomeningocele aged 5-12 years initially treated by a selective policy, seven (6.5%) achieved spontaneous urinary continence, five with normal micturition and two with urgency. All had positive conus reflexes and incomplete cord lesions which, with one exception, comprised motor as well as sensory sacral sparing. PMID- 1599307 TI - Types of psychiatric treatment. Change the family, change the child? PMID- 1599308 TI - The autonomic nervous system--a role in sudden infant death syndrome. PMID- 1599309 TI - Biological role of lactoferrin. PMID- 1599310 TI - Does growth hormone treatment improve final height attainment of children with intrauterine growth retardation? PMID- 1599311 TI - Kawasaki disease. PMID- 1599312 TI - Late intravenous gammaglobulin treatment in Kawasaki syndrome. PMID- 1599314 TI - Imposed upper airway obstruction in small children. PMID- 1599313 TI - Inherited metabolic diseases in the sudden infant death syndrome. PMID- 1599315 TI - Reducing the risk of cot death. PMID- 1599316 TI - ABC of child abuse. PMID- 1599318 TI - Coroner's records of accidental deaths. PMID- 1599319 TI - Health for all children. PMID- 1599317 TI - Effects of body temperature on respiratory rate in young children. PMID- 1599320 TI - Intraosseus infusion. PMID- 1599321 TI - Subdural fat effusion complicating parenteral nutrition. PMID- 1599322 TI - Familial asplenia. PMID- 1599323 TI - Birthweight ratio in public health. PMID- 1599324 TI - Growth performance of affluent Indian children under 5 years of age. PMID- 1599326 TI - Gastrointestinal complications associated with dexamethasone treatment. PMID- 1599325 TI - Toxic shock-like syndrome due to Streptococcus pyogenes. PMID- 1599327 TI - [Pacemakers]. PMID- 1599328 TI - [Coronary angioplasty as the treatment in different myocardial ischemic syndromes: a report of 121 consecutive cases]. AB - In 121 patients (93 males, mean age 53.9 years), percutaneous transluminal coronary angioplasty (PTCA) of 140 lesions was performed as treatment of symptomatic, single or multiple vessel disease, with the following clinical syndromes: stable angina pectoris (Group I) in 59 cases (48.8%), unstable angina (Group II) in 40 (33%), and angina or residual ischemia after thrombolysis for myocardial infarction (MI) (Group III) in 22 patients (18.2%). PTCA was successfully accomplished in 123 of 140 segments (87.8%), with a reduction in mean luminal stenosis from 87.3 +/- 13% (range 70-100) to 15 +/- 10% (range 0-30, p less than 0.00001). Successful results were obtained in 85.9% of patients (104/121) and they were 84.7%, 82.5% and 95.5% in Groups I, II and III, respectively. The procedure failed in 17 cases (14.0%), and within this group, 14 complications occurred (11.6%): 2 deaths (1.6%), 3 cases of MI, acute closure in 4, and emergency coronary bypass surgery in 5 patients. Late evaluation (6-8 months) revealed clinical and functional improvement in 71/98 patients (72.4%), and recurrent ischemic symptoms (no improvement) in 27 cases. Coronary angiography performed in 20, showed restenosis in 10, and progressive disease in 7 patients. In conclusion, PTCA is an effective therapeutic option in selected cases of symptomatic ischemic heart disease with suboptimal results to medical management alone. PMID- 1599329 TI - [The surgical treatment of cardiac myxomas: 10 years of experience]. AB - Over a ten-year period (September 1980-July 1990) 3172 patients underwent open heart surgery in our hospital. Twenty five patients (0.78%) had a cardiac myxoma. There were 18 female and 7 male patients, mean age of 32.3 +/- 21 years (4-61). Left atrial myxomas were diagnosed in 18 patients, left ventricular myxoma in three, right atrial myxoma in two, and one in right ventricle; there was a biatrial myxoma in one case, another had biatrial and left ventricular myxoma. The clinical manifestations of right sided myxomas was congestive heart failure. Patients with left myxoma frequently presented embolic episodes. Myxoma diagnosis was made by means of chest films, EKG and two-dimensional echocardiography which proved effective in twenty four of our patients; cardiac catheterization was performed in ten of them. Symptoms before diagnosis lasted an average of 16.3 months and mean time from diagnosis to operation was 6.6 days. Different surgical approaches are analyzed and discussed. Concomitant surgical procedures were performed in five patients: mitral annuloplasty in one, mitral valve replacement in four (two biological and two mechanical prosthesis). In eight patients the resulting septal defect due to resection of pedicle was closed with pericardial or dacron patches. There were two operative deaths due to pulmonary emboli in one and multiple organ failure in other. Cardiac myxoma is the more frequent primary neoplasm of the heart; its "benign" nature is doubtful; cure by surgical excision can be considered in vast majority of patients and its morbidity is reasonably low. PMID- 1599331 TI - [Rupture of the interventricular septum in acute myocardial infarct]. AB - Ventricular septal rupture in patients with acute myocardial infarction is not a common complication. It was found in 20 patients of 4298 admitted to the coronary care unit of the Instituto Nacional de Cardiologia Ignacio Chavez from January 1980 to March 1991. The diagnosis was made by right heart catheterization if 85%, by echocardiography in 35% and by postmortem study in 15% of the patients. Mortality was 70%. In all patients the functional class worsened after the rupture, from class I to III or IV. There were not significant differences in mortality in relation to risk factors, or hemodynamic findings. Mortality was higher in older patients, females and patients with anterior myocardial infarction. Angiographic studies did not increase mortality and are necessary to establish an early surgical treatment. PMID- 1599330 TI - [Caudal-angle aortography. Its usefulness for defining the coronary anatomy in cases of transposition of the great vessels]. AB - With the purpose of obtaining an accurate definition of coronary arteries anatomy in complete transposition of the great arteries (concordant atrio-ventricular connection and discordant ventriculo-arterial connection), we performed a new angiographic technique in 14 patients with d-transposition of the great arteries and 1 patient with double-outlet right ventricle. This technique consists of using a balloon catheter with the frontal X ray tube cine-angiographic camera in caudal angulation (about 45 degrees), with balloon occlusion of the ascending aorta during the injection of the contrast medium. The results were compared with echocardiograms and surgical results. In all our cases, except 2, the technique gave us a very clear definition of the coronary anatomy and we were able to define the origin and course of the coronary arteries without difficulty. In the most common coronary artery pattern, the left coronary artery arose from sinus #1 (left aortic sinus) and gave origin to the anterior descending and left circumflex arteries, while the right coronary artery arose from aortic sinus #2 (right aortic sinus). In our series, the coronary arteries always originated from one or both facing sinuses of the aorta and the angiographic correlation with the surgical reports was accurate in all the cases. The anatomical and angiographic findings of this series are discussed. In conclusion, we find the aortogram with caudal angulation a very useful technique to improve the visualization of coronary anatomy in d-transposition of the great arteries, which has surgical significance in those cases which are candidates for anatomical correction. PMID- 1599333 TI - [Frustration and body image in children with and without congenital cardiopathy]. AB - The aim of the present study was to determine the existence of differences on the type of response to frustration and disintegration of body image among children with congenital heart diseases (hospitalized and out patients) with or without symptomatology and children without heart disease. The study was performed in the outpatient clinic and the pediatric cardiology ward of the Instituto Nacional de Cardiologia "Ignacio Chavez". Two tests were used: The Rosenzweig picture frustration test for children (PFT) and the human figure drawing (HFD) of Elizabeth Koppitz. No differences were found regarding the type of response to frustration, differences between groups were present in only two emotional items of the HFD. We conclude that children with congenital heart disease have special capabilities that enable them to respond to illness in adaptative ways. PMID- 1599332 TI - [Dynamic intracavitary echoes studied by transthoracic and transesophageal echocardiography]. AB - One hundred consecutive echocardiograms performed on adults using transthoracic and transesophageal (TEE) transducers were analyzed in order to determine the prevalence of spontaneous contrast (SC) and the factors associated with it. Indications for study included complex congenital cardiopathy, evaluation of valve lesions or prosthetic valves, dissecting aortic aneurysm, cardiac masses and evaluation of ventricular function. SC was observed only with TEE and appeared in 25% of cases, most frequently in left atrium. Factors associated with contrast included mitral valve disease and replacement, ventricular dysfunction, left atrial dilatation and atrial fibrillation. An important relationship existed between SC and presence of thrombi. Atrioventricular valvular regurgitation was not associated with SC. Results are compared with those of previous series. PMID- 1599334 TI - [The use of endocavitary fulguration in the treatment of common auricular flutter]. AB - Between April 1990 and July 1991, 10 patients, were fulgurated after right atrial endocardial mapping with the purpose of destroying or modifying the site of origin of atrial flutter. Mean age, 47 years old (23-61), 9 males. All patients suffered "common" atrial flutter episodes with very rapid ventricular response (greater than or equal to 150 beats per minute) refractory to pharmacological therapy. All patients had pathologic potentials with prolonged duration between 90 and 160 ms (m = 109) which preceded other reference electrodes in the high right atrium and His position. Electrical stimulation from that zone provoked the capture entrainment and termination of the flutter; the same configuration of the arrhythmia was obtained with electrical stimulation from the suspected zone. With the catheter in that situation one or two direct current cathodic, unipolar shocks were given with energy of 60-150 Joules (m = 117). In the follow up (16-73 weeks), 8 patients are free of symptoms without drugs, one suffered a new episode after 7 weeks, His fulguration was performed and a permanent pacemaker implanted. The other patient has failed two session and is still on treatment. PMID- 1599335 TI - [The treatment of intranodal tachycardias with intracavitary fulguration]. AB - The electrical ablation of the His bundle with proximal intracardiac shocks of low energy was performed through an electrical catheter, to 14 patients with AV nodal reentry tachycardias refractory to pharmacological therapy, to whom at least 3 antiarrhythmic drugs were previously administered. The electrical energy applied oscillated between 10 to 150 Joules (114 average). 11 patients (72%) recovered the normal atrioventricular conduction and in the electrophysiological evaluation was found: 1--Increase in the duration of the AH interval. 2--No existence of two AV nodal pathways. 3--Absence of retrograde conduction. 4- Impossibility to induce tachycardia. The PR interval was prolonged (60 ms average) after the electrical shocks. These criteria defined the total effectiveness of the procedure. In the 3 remaining patients (28%) a permanent atrioventricular complete block was induced and the implantation of the permanent pacemaker was required. It was concluded that the electrical fulguration of the atrioventricular junction with low energy is an effective technique as curative treatment for intranodal reentry tachycardias, which can be applied without induction of permanent cardiac block. PMID- 1599336 TI - [Myocardial infarct and rupture of the left ventricular free wall. Some considerations on incidence, morphological characteristics and risk factors]. AB - Rupture of the left ventricle free wall is a sudden and unexpected event in myocardial infarction. It is considered the third most common cause of death, following cardiogenic shock and arrhythmias. The frequency of rupture varies because many patients may survive the initial insult of myocardial infarction. Conflicting reports regarding risk factors have been published by several authors. With these considerations in mind, the present investigation was undertaken to evaluate ventricular rupture in an autopsy population from the Instituto Nacional de Cardiologia. We analyzed the salient morphologic features and the risk factors. Our results indicated an incidence rate of 17.7% of cardiac rupture in patients who died of acute myocardial infarction and were autopsied. Ruptures are more common in elderly female patient during their first infarct, they were localized preferentially in the anterior wall and occurred within the first four days after infarction. Chance of rupture was greater in hypertensive patients, whereas a history of previous infarct protected against this contingency. PMID- 1599338 TI - [What is new about so old pulmonary thromboembolism? II]. PMID- 1599337 TI - [Relationships between weight, age and arterial pressure in the Mexican population]. AB - Arterial hypertension (AH) constitutes a public health problem. Between 15 and 30% of the population in our country has it. Age and weight have been found as major risk factors for AH but there is little investigation in this regard. We studied families of the Mexican Republic, excluding people younger than 15 years, pregnant women, and any persons having any disease that could affects HA or being under medication. We gave them a questionnaire and took the arterial tension (AT). We calculated Quetelet Index (QI) for weight. We analysed 12259 subjects. The mean arterial tension was 120/77; 123/79 and 119/76 for men and women. We observed an association between age an AT when controlled by QI; and between AT and QI controlling by age. The regression lines had a positive skew different from zero. We propose that there is a relationship between QI an AT independent of age or AT. PMID- 1599339 TI - Adherence to cholesterol-lowering diets. PMID- 1599340 TI - Medical futility. Who decides? PMID- 1599341 TI - Effects of nonsteroidal anti-inflammatory drugs on endogenous gastrointestinal prostaglandins and therapeutic strategies for prevention and treatment of nonsteroidal anti-inflammatory drug-induced damage. AB - Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for pain relief and treatment of arthritis, they can induce gastric and duodenal ulcers and life-threatening complications. The mechanisms of their anti-inflammatory action and their gastroduodenal toxic effects are related, in part, to inhibition of prostaglandin synthesis. This review article discusses prostaglandins, their functions in the gastrointestinal tract, anti-inflammatory actions of NSAIDs, and mechanisms by which NSAIDs produce gastroduodenal ulcers. Also reviewed are risk factors associated with the development of NSAID-related ulcers and pharmacologic strategies for the prevention and treatment of NSAID-induced ulcers. PMID- 1599342 TI - Improving clinical teaching. Evaluation of a national dissemination program. AB - This study assessed a dissemination approach to improve clinical teaching. We hypothesized that (1) physicians from a variety of institutions nationwide could be trained to conduct teaching improvement seminars for faculty colleagues; (2) such seminars would be perceived as highly useful; (3) pre/post self-evaluations by faculty participants and evaluations of faculty participants by house staff/students would indicate improved teaching performance. Selected medical faculty completed 1 month of facilitator training at the Stanford Faculty Development Program, Palo Alto, Calif. They then delivered teaching improvement seminars for other faculty. From 1986 to 1988, 12 facilitators from 12 institutions trained 107 faculty at their home institutions in their initial seminar series. Their seminars were rated as highly useful by participants. Both faculty self-assessments and house staff/student ratings indicated improved teaching performance. We concluded that this dissemination approach provides one possible mechanism for ongoing teaching improvement within institutions across the country. PMID- 1599343 TI - Nonpharmacologic intervention to reduce blood pressure in older patients with mild hypertension. AB - BACKGROUND: Although nonpharmacologic interventions are widely recommended in the therapy of high blood pressure in older adults, surprisingly little data exist to confirm the efficacy of these interventions in older persons. METHODS: We conducted a randomized, controlled clinical trial in persons aged 60 to 85 years with a diastolic blood pressure of 85 to 100 mm Hg. The experimental arm was a nonpharmacologic intervention combining weight reduction, sodium restriction, and increased physical activity. The nonpharmacologic intervention consisted of eight weekly group and two individual sessions during the intensive phase, followed by four monthly group sessions during the maintenance phase. The control group received no treatment during the study. Blood pressure was assessed by certified technicians (blinded to group assignment) using random zero sphygmomanometers. RESULTS: Of 56 participants randomized, 47 completed the entire 6-month trial (21 in the intervention group and 26 in the control group). Attendance at the intervention sessions was excellent. The intervention group lost more weight ( 2.1 kg) over 6 months than the control group (+0.3 kg). Trends for decreasing 24 hour urine sodium excretion in both the intervention and control groups, with greater trend in the intervention group, were not statistically significant. The intervention group experienced more reduction in systolic and diastolic blood pressure than did the control group (mean differences between groups at 6 months, 4.2/4.9 mm Hg, respectively). CONCLUSIONS: Our data indicate that a nonpharmacologic intervention will lower systolic and diastolic blood pressure levels in older people with borderline or mild elevations of diastolic blood pressure. PMID- 1599344 TI - Saturated fats, cholesterol, and dietary compliance. AB - BACKGROUND: Lack of response to a cholesterol-lowering diet can be caused by physiological nonresponsiveness, inadequate knowledge, or inability to change dietary habits (poor compliance). The purpose of this study was to evaluate the dietary compliance of hyperlipidemic individuals who received intensive initial dietary education and followup, and who showed an initial reduction of their plasma cholesterol levels. METHODS: One hundred five individuals with fasting cholesterol levels of 5.17 mmol/L (200 mg/dL) or greater received intensive education and follow-up on the American Heart Association Step I diet during an initial 12-week period. The participants provided 3-day dietary records every week, and fasting lipoprotein analysis was performed biweekly. Six months after termination of this period, the subjects were requested to return for a follow-up evaluation of their lipoprotein profile and dietary adherence. RESULTS: Seventy three (70%) of the subjects returned for a follow-up evaluation of lipoprotein cholesterol levels. Of these, 42 (58%) had a 10% or greater average initial decrease in total cholesterol levels at weeks 3 and 4 ("baseline"), and they were considered to be "high responders." At the 6-month follow up, the average plasma cholesterol level in these responders remained 6.4% below that at entry level, but it had increased by 19% compared with baseline values (6.30 mmol/L [244 mg/dL] vs 5.43 mmol/L [210 mg/dL], respectively). Corresponding significant increases at 6 months were found in high-density lipoprotein cholesterol (8%), low-density lipoprotein cholesterol (16%), and very-low-density lipoprotein cholesterol (66%) levels. Analysis of dietary histories revealed that dietary cholesterol and percent calories from fat increased significantly, but remained within the recommended guidelines. However, the increase in percent calories from saturated fat (from 10.0% +/- 0.5% to 14.4% +/- 1.0% [mean +/- SEM]) deviated markedly from these guidelines. CONCLUSIONS: The results suggest the long-term compliance to the reduction of dietary saturated fat remains a problem, even in individuals who receive intensive initial training and show an early favorable response. Follow-up evaluation of hyperlipidemic patients who are receiving dietary therapy should take into account this behavioral pattern. It remains to be determined whether continuing supervision and better nutritional labeling will facilitate dietary compliance. PMID- 1599345 TI - Marital aggression. Impact, injury, and health correlates for husbands and wives. AB - The overall aim of the current study was to comprehensively evaluate the prevalence, impact, and health correlates of marital aggression in a clinical sample of maritally discordant couples seeking psychological treatment. Participants were 93 consecutively presenting clinic couples and 16 maritally satisfied matched control couples from the community. Overall, 71% of clinic couples reported at least one act of marital aggression during the past year. Although 86% of the aggression reported was reciprocal between husbands and wives, impact and injuries sustained as a function of this aggression differed between husbands and wives. Specifically, wives were more likely than husbands to be negatively affected and to sustain severe injuries (eg, broken bones, broken teeth, or injury to sensory organs). Additionally, wives who experienced marital aggression reported clinical levels of depressive symptomatology. Recommendations are offered and risk markers are identified to improve detection by physicians of patients who may be involved in violent marriages. PMID- 1599346 TI - Inquiry about victimization experiences. A survey of patient preferences and physician practices. AB - BACKGROUND: It is unknown whether patients want primary care physicians to inquire about physical abuse (PA) or sexual abuse (SA) or how frequently physicians make such inquiries. METHODS: To determine patient preferences and physician practices, we surveyed 164 patients and 27 physicians at private and public primary care sites. Data were collected using confidential, anonymous, written, multiple-choice questionnaires and were evaluated using univariate analysis. RESULTS: Among patients, routine PA inquiry was favored by 78% and routine SA inquiry was favored by 68%. Only 7% were ever asked about PA and 6% about SA. A history of PA was reported by 16% and a history of SA by 17%. Ninety percent believed physicians could help with problems from PA and 89% felt physicians could help with problems from SA. Among physicians, one third believed that PA and SA questions should be asked routinely. However, SA inquiries were never made by 89% at initial visits or by 85% at annual visits. Physical abuse inquiries were never made by 67% at initial visits, or by 60% at annual visits. Eighty-one percent believed they could help with problems associated with PA and 74% with SA. CONCLUSIONS: Most patients favor inquiries about physical and sexual abuse and believe physicians can help with these problems. Physicians believe they can help with these problems though they frequently do not inquire. PMID- 1599347 TI - The clonidine suppression test for pheochromocytoma. A review of its utility and pitfalls. AB - OBJECTIVE: The intent of this study is to retrospectively evaluate our experience, as well as all published information, regarding the clonidine suppression test to determine its utility, accuracy, and safety in the diagnosis of pheochromocytoma. PATIENTS AND METHODS: All 22 patients (including four with pheochromocytoma) evaluated at a major military referral hospital with the clonidine suppression test for suspected pheochromocytoma for more than 6 years were retrospectively reviewed. All published series of patients similarly evaluated were also critically reviewed. RESULTS: All studies confirm that a nonstressed plasma norepinephrine of more than 2000 pg/mL is diagnostic of pheochromocytoma. In those patients with a plasma norepinephrine of less than 2000 pg/mL, the clonidine suppression test is 92% accurate in diagnosing pheochromocytoma when the normal response to clonidine is defined as total plasma catecholamines of less than 500 pg/mL. Its accuracy diminishes in patients with low baseline plasma catecholamine levels, who may better be tested with a stimulatory test (ie, glucagon). The use of diuretics, beta-blockers, and antidepressants may cause false-positive results or severe hypotension during the clonidine suppression test. Those previously treated with clonidine or with baroreceptor dysfunction may also be prone to severe hypotension, but this complication is otherwise uncommon after acute clonidine ingestion. CONCLUSION: Although it is rarely necessary for the diagnosis of pheochromocytoma, the clonidine suppression test is an accurate and safe test in a select group of patients. PMID- 1599348 TI - Randomized controlled study of a retiree health promotion program. The Bank of American Study. AB - The initial results of a 12-month controlled trial of a health promotion program in 5686 Bank of America retirees, randomized into full program, questionnaire only, and insurance claims only groups, were analyzed to determine whether the health promotion program was effective. Comparisons were between program and questionnaire only groups for self-reported health habit changes, health risk scores, medical care utilization, and days confined to home, and between all groups for insurance claims data. The intervention, or full program, included health habit questionnaires administered every 6 months, individualized time oriented health risk appraisals, personal recommendation letters, self-management materials, and a health promotion book. Twelve-month changes in health habits, health status, and economic variables favored the full program group in 31 of 32 comparisons and were statistically significant at the .05 level in two-tailed tests in 19 comparisons and at the .01 level in two-tailed tests in 13 comparisons. Over 12 months, overall computed health risk scores decreased by 4.3% in the full program experimental group and increased by 7.2% in the questionnaire only control group. Total direct and indirect costs decreased by 11% in the experimental group and increased by 6.3% in the questionnaire only control group. Analysis of claims data confirmed these trends. A low-cost health promotion program for retirees was effective in changing health behaviors and has potential to decrease health care utilization. PMID- 1599349 TI - Predicting postoperative pulmonary complications. Is it a real problem? AB - To identify predictors of postoperative pulmonary complications, a population of 278 patients, mainly hypertensive and diabetic patients undergoing elective general surgery was studied; 60% of the patients underwent abdominal surgery. Of the 278 patients, 6% had postoperative pulmonary complications: 3% had radiographic evidence of infiltrates or segmental atelectasis and 3% had clinical evidence of atelectasis. Among the two thirds of patients undergoing abdominal surgery, only patients with underlying asthma or chronic bronchitis were at increased risk. Generally, patients with better exercise tolerance by self report, walking distance, or cardiovascular classification had lower rates. Pulmonary function tests did not help to delineate patients at higher risk of postoperative pulmonary complications. Simple clinical information provided as much data about the patients' risk as pulmonary function tests. Many of these complications occurred in patients who sustained other types of postoperative morbidity, suggesting that predicting and preventing postoperative cardiac morbidity may be the best approach to reducing postoperative pulmonary morbidity. PMID- 1599350 TI - Medical care and cost outcomes after pentoxifylline treatment for peripheral arterial disease. AB - We assessed the medical outcomes and costs associated with the pharmacologic treatment of patients with peripheral arterial disease (PAD) in a population based historical cohort study of patients enrolled in a health maintenance organization. For up to 2 years, we compared 58 patients who used therapeutic amounts of pentoxifylline with a comparison group of 112 patients who received a minimal subefficacious trial of pentoxifylline. Medical records data were used to assess and control for the severity of PAD and other potentially confounding factors. Continuous use of a therapeutic amount of pentoxifylline during an initial 120-day period significantly reduced the incidence of PAD-related invasive therapeutic and diagnostic procedures in the first year of follow-up (adjusted relative risk, 0.35; 95% confidence interval, 0.12 to 0.99). However, there were no significant differences in the risk of a PAD-related hospitalization or cost of PAD-related care between continuous pentoxifylline users and the comparison group. Pentoxifylline therapy may reduce the risk of vascular surgery while not increasing the total cost of PAD care. PMID- 1599352 TI - Single-dose compared with 3-day norfloxacin treatment of uncomplicated urinary tract infection in women. Canadian Infectious Diseases Society Clinical Trials Study Group. AB - BACKGROUND--This study was undertaken to determine whether therapy for acute uncomplicated urinary tract infection in women with single-dose therapy with norfloxacin was superior to 3 days of norfloxacin therapy in efficacy or adverse effects. METHODS--The study was a multicenter, prospective, randomized, double blind trial. Women with acute, uncomplicated urinary tract infection were randomized to receive norfloxacin, 800 mg as a single dose or 400 mg twice daily for 3 days. Clinical and laboratory evaluations were obtained before therapy and at days 3 and 7 and 4 to 6 weeks after initiation of therapy. RESULTS--The 83 subjects for whom data could be evaluated who received 3-day therapy had significantly improved outcome compared with the 73 subjects for whom data could be evaluated who received single-dose therapy at 3 days and 7 days after initiation of therapy. At 4 to 6 weeks, 88% of subjects who received 3 days of therapy remained cured, compared with 78% who received single-dose therapy. Three day and single-dose therapy were equivalent for Escherichia coli infection, but single-dose therapy was significantly less effective for other organisms, primarily because of failure of treatment of Staphylococcus saprophyticus infection. Women older than 40 years were significantly less likely to be cured with either treatment regimen and with single-dose therapy. Adverse effects were similar for both treatment regimens. CONCLUSIONS: -Three days of norfloxacin therapy is more effective than single-dose therapy for women with acute, uncomplicated urinary tract infection. The two regimens are equally effective for E coli infection, but single-dose therapy is ineffective for S saprophyticus. PMID- 1599351 TI - Proteinuria, renal impairment, metabolic control, and blood pressure in type 2 diabetes mellitus. A 14-year follow-up report on 195 patients. AB - BACKGROUND: The deleterious effect of hypertension on the course of diabetic retinopathy and the protective influence of antihypertensive therapy are well known. There is, however, little information about the long-term effect of different levels of blood pressure within the normal range on the evolution of renal function in type II diabetes. METHODS: One hundred ninety-five young normotensive patients with recent-onset type II diabetes, normal renal function, and no proteinuria were followed up for 14 years. Plasma glucose, creatinine, and urinary protein levels and blood pressure were determined periodically. RESULTS: Thirty patients developed hypertension; among them, 18 developed proteinuria (0.3 g/L). Among 144 patients who remained normotensive, 30 developed proteinuria. The mean decline in renal function (decline in reciprocal creatinine [100/creatinine level], expressed as a percentage of the initial value) was 26% for normotensive patients, 43% for normotensive patients with nephropathy, 39% for hypertensive patients, and 52% for hypertensive patients with nephropathy. The degree of metabolic control was not associated with the presence of proteinuria or with the severity of renal impairment. There was a significant association between the mean blood pressure over the whole observation period and the degree of impairment in renal function. This association was significant also in the patients who remained normotensive with and without proteinuria. CONCLUSIONS: Minor elevation of blood pressure as well as values in the upper normal range may be associated with acceleration of renal damage in type II diabetes. PMID- 1599353 TI - Cardiovascular effects of pseudoephedrine in medically controlled hypertensive patients. AB - BACKGROUND: Oral sympathomimetics are effective in the treatment of nasal congestion through stimulation of alpha-adrenergic receptors in the blood vessels of the nasal mucosa. This vasoconstrictor activity has resulted in the general recommendation that such pressor amines not be used in patients with hypertension. No prospective studies have examined the safety of sustained release pseudoephedrine in hypertensive patients. METHODS: Volunteers (N = 28) with controlled hypertension participated in a randomized, double-blind, placebo controlled, crossover study that examined the cardiovascular effects of 120 mg of sustained-release pseudoephedrine taken on a twice daily basis. Physician investigators measured blood pressure and heart rate using mercurial sphygmomanometers during acute and steady-state phases. Compliance was verified with pill counts and serum drug levels. Symptom questionnaires were completed by the volunteers. RESULTS: While a strong statistical correlation was found over time, with minimal increases in mean arterial pressure and heart rate, pseudoephedrine administration did not result in statistically significant changes in any cardiovascular parameter. Mild disturbances in sleeping pattern and urinary retention in some male subjects were the only significant symptoms detected. CONCLUSIONS: We conclude that while sustained-release pseudoephedrine appears safe for the majority of medically controlled hypertensive patients without statistically significant effects on blood pressure or heart rate our studies did show an upward trend in these parameters which, in a larger population of hypertensive patients, may prove to be clinically significant. PMID- 1599354 TI - Plague. A clinical review of 27 cases. AB - We reviewed the medical records of 27 patients with plague seen at the Gallup (NM) Indian Medical Center between 1965 and 1989. Nineteen patients had bubonic plague and eight had septicemic plague. Three patients with septicemic plague and three with bubonic plague died. The patients presented with five different clinical pictures. Ten patients presented with classic signs of plague, five with the appearance of an upper respiratory tract infection, five with a nonspecific febrile syndrome, four with the appearance of a gastrointestinal or urinary tract infection, and three with the appearance of meningitis. Blood cultures were positive in 24 of 25 cases, and bubo aspirate cultures were positive in 10 of 13 cases. All six patients who died were under 30 years old, and all the deaths were related to a failure to treat initially with an antibiotic appropriate for plague. Plague is a treatable disease, but clinicians must have a high index of suspicion and give appropriate antibiotics at the earliest possible time to patients whose presentation suggests plague. PMID- 1599355 TI - Body mass index and body girths as predictors of mortality in black and white women. AB - BACKGROUND: The high prevalence of obesity in black women has been hypothesized to contribute to higher rates of coronary heart disease and total mortality. Investigators have recently refined the study of obesity by differentiating anatomic patterns of the physical location of adipose tissue on the body. We examined fat patterning as a predictor of mortality in black women. METHODS: Body mass index (BMI) and body girths were examined as predictors of all-cause and coronary heart disease mortality during 25 to 28 years of follow-up in black and white women in the Charleston Heart Study. RESULTS: The BMI was associated with all-cause and coronary heart disease mortality in white, but not black, women. After controlling for differences in BMI, the risk of all-cause mortality was greater in white women with larger chest and abdominal girths, while midarm girths were inversely associated with mortality. The hazard at the 85th percentile relative to the 15th percentile of abdomen/midarm ratio was 1.44 in models that included BMI, education, and smoking as covariates. In black women, the girths were not predictive of either all-cause or coronary heart disease mortality. CONCLUSIONS: The failure of BMI and fat patterning to predict mortality in black women challenges previously held assumptions regarding the role of overweight in the higher mortality experienced by black women. PMID- 1599356 TI - The potential role of thrombolytic therapy in venous thrombosis. AB - BACKGROUND: Anticoagulant therapy for lower extremity deep-vein thrombosis (DVT) has been shown to reduce mortality from pulmonary embolism, but subsequent morbidity from the postthrombotic syndrome remains high. Thrombolytic therapy produces higher lysis rates of venous thrombi than heparin alone. Some studies suggest a lower incidence of postthrombotic sequelae after early use of streptokinase. These potential benefits are limited to those patients without contraindications for this therapy. METHODS: For the past 3 years we have prospectively studied patients with DVT documented by duplex scanning. The records of these patients were reviewed to determine what proportion of this population would have been candidates for thrombolytic therapy. For this analysis, contraindications to the use of thrombolytic agents included: (1) recent surgery (less than 1 month); (2) recent major trauma; (3) active or recent bleeding; (4) brain disease (cerebrovascular accident, brain tumor, arteriovenous malformation); (5) pregnancy; and (6) bleeding diathesis. Also, patients with prior ipsilateral DVT and those with acute symptoms present for 7 or more days were not considered to be candidates for thrombolytic therapy. RESULTS: A contraindication to thrombolytic therapy was present in 194 (93%) of 209 patients with a diagnosis of DVT, including four patients with a relative contraindication. Two or more contraindications were present in 65 cases (31%). Recent surgery was the most frequent factor precluding therapy, being present in 71 patients. A history of DVT in the affected leg was present in 45 patients. CONCLUSIONS: Only 15 (7%) of 209 patients with DVT exhibited no contraindications for thrombolytic treatment. Only a small fraction of patients with venous thrombosis will be potential candidates for this therapy. PMID- 1599357 TI - Fever in pheochromocytoma. AB - BACKGROUND: Fever is an infrequently reported finding in patients with pheochromocytoma. Fever in patients with pheochromocytoma may be caused by the tumor, an infection or other factors, each of which will dictate different treatment strategies. METHODS: To determine the incidence, cause, and significance of fever in patients with pheochromocytoma, we reviewed the medical records of 50 hospitalizations of 48 patients. Patients were categorized by the presence or absence of fever. Body temperature elevation, duration of hospitalization in the period prior to surgery or death, age, sex, race, other conditions that could have been responsible for the febrile episode (comorbid events), location, gross and microscopic features of the tumors, and plasma and urine hormone levels were tabulated. The results were compared between the two groups of patients. RESULTS: Fever was present in 14 (28%) of 50 hospitalizations, seven patients (50%) of whom had pheochromocytoma multisystem crisis. Patients with fever and pheochromocytoma were significantly more likely to have a comorbid event, larger tumor, necrosis within the tumor, higher urinary metanephrine levels, longer duration of hospitalization prior to surgery, and to be non-white. Comorbid events included both infectious and noninfectious potential causes of fever. CONCLUSIONS: Fever is common in patients with pheochromocytoma. The causes may be multifactorial and often include an associated illness. A thorough search for coexisting disease is indicated. While fever may prolong hospitalization, it does not portend a disastrous outcome. PMID- 1599358 TI - Undiagnosed migraine headaches. A comparison of symptom-based and reported physician diagnosis. AB - BACKGROUND: Although migraine headaches are a common cause of temporary disability, many people with migraine have not been diagnosed. In a sample of the US population, we sought to determine the proportion of migraineurs diagnosed by a physician and to identify the headache characteristics and sociodemographic profiles associated with undiagnosed migraine. METHODS: A mail questionnaire survey was sent to 15,000 US households, selected from a panel to be representative of the US population. Of a total study base population of 23,611, excluding 3043 subjects less than 12 years of age and respondents with unreported gender, we analyzed data for 20,468 subjects aged 12 to 80 years. Migraine diagnoses were assigned on the basis of reported symptoms by means of operational diagnostic criteria. Physician diagnosis of migraine was ascertained on the basis of self-report. RESULTS: Forty-one percent of female and 29% of male migraineurs reported having been diagnosed by a physician. Diagnosis was more likely in females, in people with high income levels, and in individuals who reported migraine associated with aura, vomiting, or disability. Of the undiagnosed subjects, 80% experienced at least some headache-related disability. CONCLUSIONS: Results of this survey indicate that the majority of people with migraine in the United States do not report having been diagnosed by a physician. Given the high proportion of undiagnosed subjects with headache-related disability, efforts to improve the diagnosis and treatment of migraine are recommended. PMID- 1599359 TI - Circadian distribution of in-hospital cardiopulmonary arrests on the general medical ward. AB - BACKGROUND: A circadian pattern has been convincingly demonstrated for the onset of many outpatient ischemic vascular events. A morning peak exists for the onset of acute myocardial infarction, sudden cardiac death, reversible myocardial ischemia, and ischemic stroke. Data regarding circadian patterns of disease in hospitalized patients, however, are lacking. We examined in-hospital cardiopulmonary arrest (CPA) occurring on the general medical ward to determine if a circadian distribution existed in time of onset. METHODS: All CPAs that occurred during a 9-month period and met entry criteria were included for study. The day was divided into 4-hour intervals and analyses were performed for evidence of periodicity in time of onset. The CPAs were then divided into those that were "expected" and those that were "unexpected," and further analyses of periodicity were performed. RESULTS: For the total study population (137 patients), a primary peak frequency of CPA occurred during the interval from 4 to 7:59 AM, and a secondary peak frequency occurred during the 8 to 11:59 PM interval. A minimum frequency occurred during the midnight to 3:59 AM interval. The onset of unexpected CPA peaked during the 4 to 7:59 AM interval, and expected CPA followed no circadian pattern. CONCLUSIONS: Our analysis of CPA occurring in patients hospitalized on the general medical ward demonstrated a circadian pattern of onset that favored the early-morning hours. This pattern is predominantly due to unexpected CPA. If further study confirms our observations, changes in the prophylaxis of in-hospital CPA and adjustments in staff responses to its occurrence may be indicated. PMID- 1599360 TI - The clinical impact of culturing central venous catheters. A prospective study. AB - The semiquantitative culture technique is a standard procedure for the laboratory diagnosis of catheter-associated infections and catheter-associated bacteremia. In a prospective observational study, we evaluated the clinical impact of the semiquantitative culture results on the treatment of the patient. Clinical impact was defined as a change in diagnosis or therapy on the basis of the semiquantitative culture result. One hundred fifty-seven catheters consecutively submitted from the surgical intensive care unit to the laboratory were studied. In 96% of the episodes, no clinical impact was observed. In the other 4%, clinical decisions were guided mainly by the concurrent positive blood cultures. Newer laboratory techniques that do not require removal of the catheter are needed to guide therapeutic decisions. PMID- 1599362 TI - Complete recovery after massive ethylene glycol ingestion. AB - We treated a 64-year-old man who recovered completely from a massive antifreeze ingestion with ethylene glycol levels well above those of previously described survivors. Rapid and aggressive treatment of the patient with recognized methods, including hemodialysis, resulted in the favorable outcome. PMID- 1599361 TI - The use of hepatobiliary scintigraphy in patients with acalculous biliary colic. AB - Twelve patients with biliary colic had no evidence of gallstones but underwent cholecystokinin-augmented hepatobiliary scintigraphy that revealed gallbladder ejection fractions of less than 35%. All 12 patients underwent cholecystectomy. Biliary colic was relieved in all patients at a mean postoperative follow-up of 2.5 years. The biliary colic in these patients was probably caused by abnormal gallbladder emptying, itself apparently produced by either cystic duct obstruction or abnormal motility. Biliary abnormality was seen at operation in most patients, and all patients had abnormalities of the gallbladder or cystic duct seen grossly or histologically. These abnormalities included cystic duct stenosis or adhesions, chronic inflammation, and cholesterolosis. PMID- 1599363 TI - Interpretation of hypercalcemia in a patient with end-stage renal disease. AB - Patients with both end-stage renal disease and multiple myeloma are prone to changes in ionized calcium homeostasis that may have grave consequences. However, only total calcium level is reported in most routine laboratory testing, with various algorithms used to derive the physiologically important ionized or free calcium level to guide treatment. We studied a patient with multiple myeloma undergoing long-term hemodialysis who presented with a markedly elevated total calcium level but with only minimal elevation in the ionized calcium level. All of the commonly used algorithms would have overestimated the ionized calcium level, and some of these might have led to inappropriate treatment. When therapy depends critically on the ionized calcium level, direct measurement is essential. PMID- 1599364 TI - Congenital neutropenia: how long? PMID- 1599365 TI - Congenital neutropenia: how low? PMID- 1599366 TI - Amebic encephalitis unlikely. PMID- 1599367 TI - False positive. PMID- 1599368 TI - Toxicologic data--sorry, wrong number. PMID- 1599369 TI - The effect of access to lethal methods of injury on suicide rates. AB - The relationship between the availability of lethal methods of injury and suicide rates is an important, but unresolved question. We investigated this relationship by prospectively classifying lethal methods according to their accessibility in the five counties of New York City. These counties have both similarities and differences in the proportion of their populations with access to specific lethal means. We then compared the age- and gender-adjusted method-specific suicide rates of these counties. There were marked differences in overall crude suicide rates among the five counties. The counties had similar suicide rates involving methods that were equally accessible to all persons in each county (eg, hanging, laceration, suffocation, and burns) as well as methods that were accessible to a smaller, but similar proportion of the population in each county (eg, firearms and drowning in waterways). Virtually all of the differences in overall suicide risk among counties were explained by differences in rates involving methods that were differentially available in the counties, principally fall from height, overdose of prescription medications, and carbon monoxide poisoning. We conclude that differences in suicide rates between communities are, in large part, due to differences in accessibility to lethal methods of injury. Therefore, systematic studies should evaluate the effect of reducing accessibility to specific lethal means on suicide rates. PMID- 1599370 TI - Multiple risk factors predict suicide in alcoholism. AB - From a study of the lives of 50 alcoholics who committed suicide, seven nonacute clinical/historical features were identified post hoc that appear to be intimately linked to suicide. They included continued drinking, major depressive episode, suicidal communication, poor social support, serious medical illness, unemployment, and living alone. This study examined whether these features are common to alcoholics generally and/or to nonalcoholics who commit suicide or if they may be specifically predictive of suicide in alcoholics. The frequencies of these factors were compared with those in an earlier sample of 32 alcoholics who committed suicide, then with data from two St Louis studies of living alcoholics and a cohort of individuals with major depressive disorder who committed suicide. The frequency of the identified items was replicated among the 32 alcoholics in a larger community sample of individuals who committed suicide. The white men from those two samples of alcoholics who committed suicide were then combined for the advantage of sample size. Six of the seven factors could be compared with a population survey sample of 106 living alcoholics and five with a clinically identified sample of 142 living alcoholics. All compared factors were significantly more frequent among those who committed suicide than among controls. Any four of the six factors identified 46 (69%) of the 67 individuals who committed suicide with few false-positive results among the controls. Regarding all seven of the identified factors, 54 (81%) of the 67 men and 64 (83%) of the entire sample of 82 individuals who committed suicide had four or more risk factors. Alcoholic women and blacks showed the same pattern as white men.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599371 TI - Contrast of treatment-seeking and untreated cocaine abusers. AB - Eighty-nine cocaine abusers seeking treatment were compared with 89 untreated cocaine abusers recruited through chain referral. The community users reported significantly higher levels of polysubstance abuse, fewer negative consequences of cocaine use, lower levels of participation in adult social roles, and greater involvement with the legal system and illegal activities. The two groups were found to be comparable on measures of severity of cocaine use, utilization of self-control strategies to restrict cocaine use, and rates of current and lifetime psychiatric disorders. Findings suggest that high rates of psychiatric comorbidity among cocaine abusers are not uniquely a feature of clinical populations. Moreover, many of the untreated cocaine abusers were found to be heavy users who might benefit from treatment but who tended to minimize the negative consequences of their cocaine use and who lacked support and pressure to enter treatment. PMID- 1599372 TI - Mentally disordered offenders who push or attempt to push victims onto subway tracks in New York City. AB - Violent offenders who pushed or attempted to push victims onto the subway tracks in New York City during the 17-year period from 1975 through 1991 were studied. Forty-nine incidents involving 52 victims were identified during this period. Of 36 perpetrators who acted alone, 25 (69%) were referred for psychiatric evaluation and treatment, as was one member of an offending gang. Data concerning 20 of these 26 offenders and their crimes were collected. At the time of the offense, 19 (95%) of these offenders were psychotic, and 13 (65%) were homeless. Most of these offenders had extensive histories of psychiatric hospitalization and several prior arrests and convictions, often for violent crimes. The offenders had extensive mental health and criminal histories. The victims of these crimes were always strangers. Half of the offenders killed or seriously injured victims. Since 1986, the incidence of this offense has increased, and offenders accounting for the increase are mostly psychotic and homeless. PMID- 1599373 TI - Mental disorder, intellectual deficiency, and crime. Evidence from a birth cohort. AB - Studies of criminality among patients in psychiatric hospitals and of mental disorder among incarcerated offenders have suggested an association between the major mental disorders (schizophrenia and major affective disorders) and crime. However, these investigations are characterized by notable methodological weaknesses, and, consequently, this conclusion has remained tentative. Little is known about the criminality of intellectually handicapped people. The present study examined the relationship between crime and mental disorder and crime and intellectual deficiency in an unselected Swedish birth cohort followed up to age 30 years. It was found that men with major mental disorders were 2 1/2 times more likely than men with no disorder or handicap to be registered for a criminal offense and four times more likely to be registered for a violent offense. Women with major disorders were five times more likely than women with no disorder or handicap to be registered for an offense and 27 times more likely to be registered for a violent offense. These subjects committed many serious offenses throughout their lives. The criminal behavior in over half these cases appeared before the age of 18 years. Intellectually handicapped men were three times more likely to offend than men with no disorder or handicap and five times more likely to commit a violent offense. Intellectually handicapped women were almost four times more likely to offend than women with no disorder or handicap and 25 times more likely to commit a violent offense.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599374 TI - Violence (and a message for the 90s?) PMID- 1599375 TI - Aggressive behavior: from laboratory to clinic. Quo vadit? AB - This article sets forth two theses: (1) that animal models of aggressive behavior have utility in fostering and guiding human aggression research; and (2) that clinical violence research should now focus on the severely and repetitively aggressive patients for study and therapeutic research. Animal models are reviewed in terms of typology; studies of temperament; the role of sensory cues; neuroanatomy, neurochemistry, and neuroendocrinology; studies of stress; and studies of social conditions. Examples are presented that have implications and potential utility for human research. Clinical approaches to the study of human aggressive behavior are examined and five suggestions are made to enhance the efficacy and utility of clinically relevant aggression research. PMID- 1599376 TI - The current state of psychiatry in the treatment of violent patients. AB - During the past 2 decades psychiatry has made great progress in describing patterns of violence by psychiatric patients and developing standards for the evaluation and treatment of these patients. Studies have found that roughly 10% of patients were violent toward other persons just prior to psychiatric hospitalization. Young male patients and patients in certain diagnostic groups had higher rates of violence. This report describes the proper evaluation of violent patients and proposes a model for the short-term potential of violent behavior. Psychiatry has developed guidelines for the acute treatment of violent patients using verbal intervention, physical restraint, and emergency medication. Long-term treatment relies on medication for the underlying disorder. Beyond their traditional indications, carbamazepine, propranolol hydrochloride, and lithium carbonate may be effective in diminishing violence. Some violent patients respond to long-term psychotherapy. PMID- 1599377 TI - Evolutionary biology and life-events research. PMID- 1599378 TI - Loss of cabin pressurization in U.S. Naval aircraft: 1969-90. AB - During the 22-year period from 1 January 1969 to 31 December 1990, there were 205 reported cases of loss of cabin pressure in US Naval aircraft; 21 were crew initiated and 184 were deemed accidental. The ambient altitudes varied from 10,000 ft (3048 m) to 40,000 ft. (12192 m). The most common reason for crew initiated decompression was to clear smoke and fumes from the cockpit/cabin (95%). The most common cause for accidental loss of cabin pressure was mechanical (73.37%), with aircraft structural damage accounting for the remaining 26.63%. Serious physiological problems included 1 pneumothorax, 11 cases of Type I decompression sickness, 23 cases of mild to moderate hypoxia with no loss of consciousness, 18 cases of hypoxia with loss of consciousness, and 3 lost aircraft with 4 fatalities due to incapacitation by hypoxia. In addition, 12 ejections were attributed to loss of cockpit pressure. Nine of the ejections were deliberate and three were accidental, caused by wind blast activation of the face curtain. Three aviators lost their lives following ejection and seven aircraft were lost. While the incidence of loss of cabin pressure in Naval aircraft appears low, it none-the-less presents a definite risk to the aircrew. Lectures on the loss of cabin/cockpit pressurization should continue during indoctrination and refresher physiology training. PMID- 1599379 TI - Peripheral and central blood flow in man during cold, thermoneutral, and hot water immersion. AB - Cardiovascular reflexes were studied during immersion in water to the chest. Cardiac output (CO) was determined by acetylene rebreathing; forearm muscle and subcutaneous blood flow by 133Xe-clearance; and cutaneous blood flow by laser Doppler. Measurements were taken in a) control situation (CTR) (subject sitting dry); b) immersed in thermoneutral (NWI); c) in cold (CWI); and d) in hot water (HWI). The overall trend was that water immersion per se increased stroke volume (SV), but mostly during NWI and CWI, where heart rate (HR) was decreased by 15%; during HWI, HR increased by 32%, the temperature effect evidently overriding the immersion effect. Insignificant increases in CO were seen in NWI and HWI (18% and 44%), and no effect in CWI. Arterial pressure and total peripheral resistance (TPR) increased significantly in CWI due to an increase in peripheral vascular resistance, while significant decreases in TPR and CPR were observed in HWI and tendencies to decreases were found in NWI. PMID- 1599380 TI - Fluid-electrolyte losses in uniforms during prolonged exercise at 30 degrees C. AB - The effects of several uniform configurations on fluid and electrolyte losses in a hot environment (30 degrees C db, 18 degrees C wb) were studied in 15 healthy males, during 6 h of intermittent treadmill exercise (1.56 m.s-1, 0% grade, 50 min.h-1, 28 km total distance). The uniforms were: the temperate battle dress uniform (BDU), two variants (C and F) of full military oriented protective posture (MOPP IV), and MOPP IV with no mask or hood (M). Sweat rate, urine volume, electrolyte losses (Na+, Cl-, K+, Mg++, Ca++) in sweat and urine, rectal temperature, mean skin temperature, heart rate, and temperature/humidity inside uniforms were measured. Observations indicated that both MOPP IV configurations (C and F) resulted in significantly greater (p. less than 0.05) fluid losses and physiological strain than BDU and M. However, there were no between-uniform differences in the total loss of any electrolyte. Total body fluid losses (kg.6h 1) and electrolyte losses in sweat (mEq.6h-1) were consistently greater than in urine. It was concluded that 6 h of exercise in uniforms at 30 degrees C can result in losses of Na+ and Ca++ which exceed the normal daily intake of these electrolytes. Supplementation of fluid, Na+, and Ca++ appears to be warranted when scenarios require 6 h or more of uniformed exposure to heat. PMID- 1599381 TI - Salivary secretion and seasickness susceptibility. AB - The salivary flow rate and composition of 2 groups of 31 subjects, one group at each extreme of the seasickness susceptibility scale, were compared. No significant differences were found between the two groups in flow rates and electrolyte concentrations of whole resting and stimulated saliva. Amylase activity and rate of secretion in resting saliva were significantly higher in subjects susceptible to seasickness as compared with nonsusceptible subjects. Also, the total protein rate of secretion in resting saliva was significantly higher in the susceptible group. The present findings could be explained in terms of higher sympathetic tone in subjects susceptible to seasickness, and salivary amylase levels might be recommended as an additional parameter in the evaluation of seasickness susceptibility. PMID- 1599382 TI - Cochlear degeneration in guinea pigs after repeated hyperbaric exposures. AB - The effects of repeated hyperbaric exposures on inner ear function and morphology in guinea pigs were investigated with auditory electrophysiological testing, histopathological and electron microscopic techniques associated with enzyme histochemical method. The results showed that repeated hyperbaric exposures, though considered "safe," did cause damage to the cochlear system. Possible causes of the pathology include direct effects of repeated compression and decompression on the ear, and the possibility of inner ear decompression sickness and barotrauma cannot be excluded. PMID- 1599383 TI - Tyrosine and its potential use as a countermeasure to performance decrement in military sustained operations. AB - We review the biochemistry and physiological role of the amino acid tyrosine in normal and stressful situations such as military sustained operations. Sustained operations consist of continuous work periods exceeding 12 h and often involve sleep loss and fatigue. These, in turn, can lead to stress, anxiety, mood deterioration, and performance decrement. Experimental data in the literature suggest that tyrosine, a precursor of the neurotransmitter norepinephrine, may be useful in counteracting any stress-related performance decrement and mood deterioration in the following way. First, various forms of stress induce brain depletion of catecholamines, especially norepinephrine, in animals. Second, brain norepinephrine levels are closely related to stress-induced performance decrement in animals. Third, the administration of tyrosine may minimize or reverse stress induced performance decrement by increasing depleted brain norepinephrine levels. The types of performance degradation expected in military sustained operations and the potential physiological role tyrosine might play in improving mood and performance are discussed. PMID- 1599384 TI - Effect of breakfast on selected serum and cardiovascular variables. AB - We compared high-density lipoprotein cholesterol (HDL-C) and other blood and cardiovascular variables of subjects when they had been fasting overnight to those values when they had eaten breakfast. The subjects were 47 men (24 to 70 years) and 34 women (23 to 63 years) who visited our laboratory on two occasions, once fasting and once after breakfast, at the same time of the morning, exactly 1 week apart. Systolic (SBP) and diastolic (DBP) pressures and heart rates (HR) were recorded, and 24-ml blood samples were obtained from an antecubital vein and analyzed for hemoglobin (Hgb), hematocrit (Hct), HDL-C, total cholesterol (T Chol), triglycerides (Trig), total calcium (T Ca), ionized calcium (Ca++), and phosphorus (P). When subjects were fasting, their SBP, HR, Trig, T Ca, and Ca++ were lower than when they had eaten breakfast. SBP, DBP, Hgb, and Trig of the women were lower than those of the men; and HDL-C and phosphorus of the women were higher. Several correlations between variables were significant only when subjects were fasting. These were SBP with age, Hct with T Ca, and T Chol with Trig. Several correlations were significant only for one sex. For the women only, SBP, DBP, and HR were correlated with T Chol, and Trig and HDL-C were correlated with T Ca. For the men only, Hgb was correlated with HDL-C, Trig, T Ca, and P; and HDL-C was correlated with Trig.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599385 TI - HIV positivity and aviation safety. PMID- 1599386 TI - Role of the Education & Training Committee. PMID- 1599387 TI - Sickle cell anemia trait in the military aircrew population. PMID- 1599388 TI - American College of Preventive Medicine certifies specialists in public health, preventive medicine, occupational medicine, and aerospace medicine. PMID- 1599390 TI - Binding of human plasminogen to basement-membrane (type IV) collagen. AB - Plasminogen, the zymogen form of the serine proteinase plasmin, has been implicated in numerous physiological and pathological processes involving extracellular-matrix remodelling. We have previously demonstrated that the activation of plasminogen catalysed by tissue plasminogen activator is dramatically stimulated in the presence of basement-membrane-specific type IV collagen [Stack, Gonzalez-Gronow & Pizzo (1990) Biochemistry 29, 4966-4970]. The present paper describes the binding of plasminogen to type IV collagen. Plasminogen binds to both the alpha 1(IV) and alpha 2(IV) chains of basement membrane collagen, with binding to the alpha 2(IV) chain preferentially inhibited by 6-aminohexanoic acid. This binding is specific and saturable, with Kd,app. values of 11.5 and 12.7 nM for collagen and gelatin respectively. Although collagen also binds to immobilized plasminogen, this interaction is unaffected by 6-aminohexanoic acid. Limited elastase proteolysis of plasminogen generated distinct collagen-binding fragments, which were identified as the kringle 1-3 and kringle 4 domains. No binding of collagen to mini-plasminogen was observed. These studies demonstrate a specific interaction between plasminogen and type IV collagen and provide further evidence for regulation of plasminogen activation by protein components of the extracellular matrix. PMID- 1599391 TI - The action of glycosylases on dopachrome (2-carboxy-2,3-dihydroindole-5,6 quinone) tautomerase. AB - It is shown that dopachrome (2-carboxy-2,3-dihydroindole-5,6-quinone) tautomerase (DCT) is a glycoprotein containing N-linked oligosaccharides. The enzymic activity can be stimulated by partial deglycosylation with a number of glycosylases such as neuraminidase, beta-mannosidase and beta-galactosidase. However, the stability of the enzyme after the hydrolytic treatment becomes lower. Thus total deglycosylation with peptide N-glycosidase F directly provokes an inactivation of DCT. The native enzyme also shows a strong affinity for concanavalin A-Sepharose. This affinity decreases after treatment with neuraminidase and/or beta-mannosidase. The DCT associated with coated vesicles seems to be mostly glycosylated, since the action of glycosylases on the enzyme obtained from these vesicles produced a similar stimulation to that with the melanosomal enzyme. Treatment of cultured melanocytes with tunicamycin elicited a decrease in the amount of active DCT inside the cells. All data suggest that the structure of the carbohydrate moiety of DCT should be very similar to, if not identical with, the structure proposed for tyrosinase by Ohkura, Yamashita, Mishima & Kobata (1984) Arch. Biochem. Biophys. 235, 63-77. PMID- 1599392 TI - Effects of recombinant monokines on hepatic pyruvate dehydrogenase, pyruvate dehydrogenase kinase, lipogenesis de novo and plasma triacylglycerols. Abolition by prior fasting. AB - 1. The effects of recombinant human tumour necrosis factor alpha (TNF) and murine interleukin-1 alpha (IL-1) on the activation state of the hepatic pyruvate dehydrogenase complex (PDHa), the activity of mitochondrial PDH kinase, hepatic lipogenesis de novo and plasma triacylglycerol (TG) concentrations were studied. 2. Monokine effects depended upon prior nutritional state. In rats fasted for 20 h or 45 h before monokine administration and refeeding (orally or with intravenous glucose), PDHa, TG and hepatic lipogenesis were not increased. In rats fed ad libitum, treatment with TNF plus IL-1 increased the contribution of hepatic lipogenesis to circulating TG to 550% of control values (P = 0.03) and plasma TG concentrations to 159% (P = 0.02), whereas PDHa increased slightly to 120% (P = 0.02) and liver glycogen content fell to 45.8% (P = 0.05) of control values. 3. Intrinsic hepatic PDH kinase activity was not changed by monokine treatment in rats fed ad libitum. 4. The increased lipogenesis de novo showed no correlation (r2 = 0.05, not significant) with hepatic PDHa in individual animals fed ad libitum. 5. In conclusion, these results suggest that monokines increase pyruvate flux through hepatic PDH in vivo in rats fed ad libitum primarily by mechanisms other than covalent modification of PDH. Prior nutritional status exerts a permissive effect for monokine stimulation of PDHa and lipogenesis, consistent with a substrate-mediated action, but the mechanism of this permissive effect remains uncertain. PMID- 1599389 TI - Control of respiration and ATP synthesis in mammalian mitochondria and cells. AB - We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599394 TI - L-arginine transport is increased in macrophages generating nitric oxide. AB - Transport of L-arginine and nitrite production were examined in the murine macrophage cell line J774. Bacterial lipopolysaccharide (LPS) induced a dose- and time-dependent stimulation of nitrite production, which was further increased in the presence of interferon-gamma. Nitrite synthesis was absolutely dependent on extracellular L-arginine and inhibited in the presence of L-lysine or L ornithine. In unactivated J774 cells L-arginine transport was saturable, with an apparent Km of 0.14 +/- 0.04 mM and Vmax. of 15 +/- 2 nmol/h per 10(6) cells. LPS (1 microgram/ml) induced a time-dependent stimulation of L-arginine transport, and after 24 h the Vmax. increased to 34 +/- 2 nmol/h per 10(6) cells. These findings indicate that activation of J774 cells with LPS produces an increase in both L-arginine transport and nitrite synthesis. The elevated rate of L-arginine transport in activated J774 cells may provide a mechanism for sustained substrate supply during enhanced utilization of L-arginine for the generation of NO. PMID- 1599395 TI - Potentiation effect of choline esters on choline-catalysed decarbamoylation of dimethylcarbamoyl-acetylcholinesterase. AB - The choline esters potentiated the choline-catalysed decarbamoylation of dimethylcarbamoyl-acetylcholinesterase in proportion to the length of acyl group, although esters containing an acyl chain longer than the hexanoyl group exhibited a corresponding decrease in the potentiation. In structural requirement analysis it was found that both the quaternary ammonium moiety and the ester bond were important for the effective acceleration of choline-catalysed decarbamoylation. In general, the respective thiocholine ester was found to be more effective than the corresponding choline ester. Whereas the binding affinity (Ka) of choline in the decarbamoylation was not significantly altered, the maximum decarbamoylation rate (kr(max.)) of choline was greatly enhanced in the presence of choline esters or thiocholine esters. Along with the above observation, the isotope solvent effect, the effect of ionic strength and the antagonism studies demonstrate that the choline esters or thiocholine esters may interact with one of peripheral anionic sites, and thereby make the choline-catalysed decarbamoylation more favourable. PMID- 1599393 TI - The role of apoproteins AI and AII in binding of high-density lipoprotein3 to membranes derived from bovine aortic endothelial cells. AB - Although binding of high-density lipoproteins (HDL) to a variety of cells in culture has been widely reported, the mechanism of this binding has yet to be fully elucidated. The aim of the current studies was to explore the roles of apoproteins (apo) AI and AII in HDL3 binding to membranes derived from bovine aortic endothelial cells. Binding studies showed that HDL3 (which contains both apo AI and apo AII) and AII-HDL3 (which contain only apo AII) bound to membranes with similar affinity (44 +/- 6 and 41 +/- 9 micrograms/ml respectively) and capacity (673 +/- 97 and 969 +/- 101 ng bound/mg of membrane protein respectively). In contrast with these results, HDL3 [AI w/o AII] (which contain apo AI, but not apo AII) bound to the membranes with a significantly higher capacity (2228 +/- 206 ng bound/mg of membrane protein) and lower affinity (65 +/ 3 micrograms/ml) as compared with HDL3 or AII-HDL3. Therefore, although both apo AI and apo AII appear capable of facilitating HDL3 binding, the mechanisms involved probably differ. A model which fits the data postulates that a common receptor exists which binds both apo AI and apo AII, and that a particle containing AII can occupy up to four receptors (partly owing to each AII molecule containing two binding domains), whereas an HDL3 [AI w/o AII] particle can occupy only one. PMID- 1599396 TI - The esterolytic activity of epidermolytic toxins. AB - The two epidermolytic toxins were shown to have intrinsic N-t-butyloxycarbonyl-L glutamic acid alpha-phenyl esterase activity. The activity was dependent on free toxin pKa values of 6.6 and 6.8 for ETA and ETB respectively. ETB incorporated 0.97 mol of radiolabelled di-isopropyl phosphorofluoridate/mol of protein with loss of esterolytic and epidermolytic activities. The correspondence of epidermolytic and esterolytic activities in ETA and ETB during thermal inactivation and reaction with di-isopropyl phosphorofluoridate, together with the inactivity of the mutant protein ETA S195G, demonstrates that the two activities are dependent on a single active serine residue in each protein. PMID- 1599397 TI - Regulation of protein synthesis in Swiss 3T3 fibroblasts. Rapid activation of the guanine-nucleotide-exchange factor by insulin and growth factors. AB - Insulin, whole serum, phorbol esters and epidermal growth factor each rapidly stimulate protein synthesis in serum-depleted Swiss 3T3 fibroblasts. The activation of protein synthesis by each of these agents is associated with stimulation of the activity of the guanine-nucleotide-exchange factor (GEF). This protein recycles the initiation factor eIF-2 by promoting exchange of GDP bound to eIF-2 for GTP. Activation of GEF is rapid, becoming maximal within 15 min. The degree of activation of GEF by these stimuli (to greater than 170% of control for insulin, serum or epidermal growth factor; 120% for phorbol dibutyrate) is more than enough to account for their effects on the overall rate of translation. Stimulation of protein synthesis and GEF activity occurs at low nanomolar insulin concentrations, indicating they are mediated through the insulin receptor. The best-characterized mechanism for regulating GEF activity is through changes in the phosphorylation of the smallest subunit of eIF-2 (eIF-2 alpha); however, none of the stimuli studied altered the level of phosphorylation of eIF-2 alpha in Swiss fibroblasts. It seems that direct regulation of GEF activity may be occurring here, and possible mechanisms for this are discussed. PMID- 1599398 TI - Kinetic barriers under steady-state conditions. AB - It is shown by analysis of a numerical example that kinetic barrier diagrams [Sudi (1991) Biochem. J. 276; 265-268] are also useful for displaying the phenomenological resistance of an enzymic turnover to net chemical fluxes observed under steady-state conditions. Most importantly, a new additivity rule is revealed by net flux profiles, which refers to limiting ('ideal') conditions. The rule states that the net fluxes that one obtains under initial steady-state conditions are strictly identical with the overall flux in the corresponding equilibrium system. This finding amounts to defining the relation between unidirectional fluxes and net fluxes, and explains why the total 'one-way flux resistance' to the overall reaction at chemical equilibrium on the one hand, and the 'net flux resistance' to both initial steady-state reactions on the other hand, have to be equal. The conclusions are claimed to be generally valid for consecutive chemical reactions. PMID- 1599399 TI - Phosphatidylcholine-dependent protein kinase C activation. Effects of cis-fatty acid and diacylglycerol on synergism, autophosphorylation and Ca(2+)-dependency. AB - A long-chain neutral phospholipid, dioleoylphosphatidylcholine, was found to support protein kinase C activation by cis-fatty acid and diacylglycerol (DAG). This effect of phosphatidylcholine (PC) is totally dependent on the presence of cis-fatty acid; PC greatly stimulates the cis-fatty acid-induced protein kinase C activity, but it does not activate protein kinase C at all, even in the presence of DAG, if cis-fatty acid is absent. DAG, however, plays a modulatory role in the presence of Ca2+; it further enhances the PC-potentiated cis-fatty acid activation of protein kinase C. Although the activities of all three protein kinase C subtypes tested (types I, II and III) are supported by this PC mechanism, type III is most sensitive to the DAG effect, and it is activated synergistically by cis-fatty acid and DAG. The potency of PC to support the synergistic activation of this subtype is equivalent to that of phosphatidylserine (PS). There are several differences, however, between PC- and PS-supported synergism observed in type III protein kinase C: (1) Ca(2+) sensitivity is different; PC requires higher concentrations of Ca2+ (10-20 microM Ca2+) than those required for PS (micromolar Ca2+); (2) PC/cis-fatty acid/DAG induced autophosphorylation of protein kinase C subtypes (types I, II and III) is very weak, whereas PS/cis-fatty acid/DAG strongly stimulate autophosphorylation of these subtypes under the conditions at which both PC and PS systems fully activate the protein kinase C in terms of histone phosphorylation. These observations suggest that a neutral phospholipid such as PC may also participate in the activation and differential regulation of protein kinase C. PMID- 1599400 TI - Evidence for an increase in positive surface charge and an increase in susceptibility to trypsin of Sarcophaga lectin (from the flesh fly, Sarcophaga peregrina) on its interaction with galactose, a hapten sugar of the lectin. AB - When Sarcophaga lectin (from the flesh fly, Sarcophaga peregrina), an insect humoral lectin, was eluted from a column of DEAE-cellulose in the presence of galactose (a hapten sugar of this lectin), it emerged at a lower salt concentration than when galactose was absent. In the presence of galactose the lectin was, in addition, more susceptible to trypsin digestion. The lectin was found to have an affinity for basic proteins such as histone H3 and sarcotoxin IA, but this property was lost in the presence of galactose. These results suggested that the lectin changes its conformation on interaction with galactose. This change is suggested to result in the exposure of some hidden lysine and/or arginine residues. PMID- 1599401 TI - Scavenger-receptor-mediated delivery of daunomycin elicits selective toxicity towards neoplastic cells of macrophage lineage. AB - Transformed cells of macrophage lineage such as J774A.1, P388D1 and IC21 take up and degrade a conjugate of the antineoplastic drug, daunomycin, with maleylated BSA with high efficiency and saturation kinetics through the scavenger receptors expressed on the surface of these cells. By contrast, transformed cells of non macrophage lineage, namely L929, EL4, Bowes melanoma and CHO (Chinese-hamster ovary), do not take up and degrade the conjugate, indicating that these cells are scavenger-receptor-deficient. In the conjugated form, about 0.1 microM-daunomycin cause 50% inhibition in the uptake of [3H]thymidine by the receptor-bearing J774A.1 cells, whereas the receptor-deficient Bowes-melanoma cells are not affected. Free daunomycin (0.1 microM) does not significantly affect the uptake of [3H]thymidine by either cell type. Treatment of cells derived from intraperitoneal tumours induced in BALB/C mice by J774A.1 cells with 0.4 microM daunomycin in the conjugated form for 5 h abolished their ability to form tumours in BALB/C mice. By contrast, transplantation of untreated cells or cells treated with free daunomycin under identical conditions led to tumour formation and subsequent death of the BALB/C mice. These results indicate that this modality for selective elimination of scavenger-receptor-bearing neoplastic cells may be useful for the treatment of histiocytic malignancies in which cells of macrophage lineage turn malignant. PMID- 1599402 TI - Uptake of injected 125I-ricin by rat liver in vivo. Subcellular distribution and characterization of the internalized ligand. AB - Subcellular-fractionation techniques were used to characterize the endocytic pathway followed by ricin in rat liver in vivo and tentatively identify the site(s) at which the ricin interchain disulphide bridge is split. After injection of 125I-ricin, hepatic uptake of radioactivity was maximum at 30 min (40% of injected dose). At 5 min, about 80% of the radioactivity in the homogenate was recovered in the microsomal (P) fraction, but later on the recovery of the radioactivity in the mitochondrial-lysosomal (ML) fractions progressively increased (50% at 30 min) at the expense of that in the P fraction. Subfractionation of the P and ML fractions on analytical sucrose-density gradients revealed a time-dependent translocation of the radioactivity from low- to high-density endocytic structures, with median relative densities at 5 and 60 min of about 1.15 and 1.16 (P fraction) and 1.19 and 1.22 (ML fraction) respectively. The late distribution of the radioactivity in the ML fraction was similar to that of the lysosomal marker acid phosphatase. Studies with co injected lactose and mannan showed that ricin was internalized mainly via the mannose receptor. In the presence of mannan, the late recovery of radioactivity in the ML fraction was decreased, and the distribution of the radioactivity associated with the P fraction was shifted toward lower densities (median relative density 1.13), indicating a different pathway of endocytosis. Analysis of the radioactivity associated with the ML and S fractions by SDS/PAGE revealed a time-dependent increase in the amount of intact A- and B-chains and low molecular-mass products. When ML fractions containing partially processed ricin were incubated at 37 degrees C at pH 5 or at pH 7.2 in the presence of ATP, only low-molecular-mass products were generated. We conclude that internalized ricin associates with endocytic structures whose size and density of equilibration increase with time, and that, although detectable in these structures, reduction of the ricin interchain disulphide bridge occurs to a large extent in the cytosol. PMID- 1599403 TI - Processing and trafficking of clotting factor X in the secretory pathway. Effects of warfarin. AB - Clotting factor X undergoes several post-translational processing steps in the liver before the protein appears in blood as the mature two-chain zymogen. In this study we have followed the factor X precursor through the secretory pathway in rat liver in order to identify the site for proteolytic processing of the precursor into a two-chain form and the site for warfarin inhibition of precursor trafficking within the pathway. Isolated rat liver Golgi apparatus was shown to harbour two single-chains of factor X precursors of 70 and 74 kDa and the heavy (50 kDa) and light chains of factor X. It was demonstrated that the two-chain factor X form was produced from a late processing form of the factor X precursor, which indicated that the site for proteolytic conversion to a two-chain form was in the trans-Golgi compartment. The 70 and 74 kDa single-chain precursors and also the light chain of the two-chain form were shown to contain the factor X propeptide which is normally removed before the coagulation factor appears in blood. The data demonstrate that intra-chain cleavage of a single chain factor X precursor in the trans-Golgi compartment can precede release of the propeptide. Warfarin was shown to affect trafficking of the factor X precursor between the endoplasmic reticulum (ER) and the Golgi apparatus. The data suggest a link between vitamin K-dependent gamma-carboxylation of the precursor and its exit from the ER. Warfarin administration resulted in accumulation of factor X precursors associated with the ER membrane. These precursors appear to be stabilized from intracellular degradation while in the ER. In contrast to the large increase in the factor X precursor concentration in the ER membrane, there was no change in the prothrombin precursor concentration as a result of warfarin action on the liver. However, intracellular turnover of the microsomal prothrombin precursor pool in warfarin-treated rats resulted in a pool of less negatively charged proteins, indicating ongoing protein synthesis but inhibition of gamma-carboxylation. The data are consistent with previous findings [Wallin & Martin (1988) J. Biol. Chem. 263, 9994-10001] suggesting that prothrombin and factor X are processed differently by the vitamin K-dependent carboxylase in the ER membrane. PMID- 1599404 TI - Processing of the phospholipid analogue phosphatidyl(N-sulphorhodamine B sulphonyl)ethanolamine by rat hepatocytes in vitro and in vivo. AB - We have investigated the processing of the non-exchangeable fluorescent phospholipid analogue phosphatidyl(N-sulphorhodamine B sulphonyl)ethanolamine (N Rh-PE) by rat liver cells. In the hepatocyte couplet system, N-Rh-PE was incorporated into the plasma membrane at 2 degrees C and readily internalized upon warming to 37 degrees C. Fluorescence was initially found to be concentrated in vesicles clustered throughout the cell, but subsequently it started to accumulate in pericanalicular vesicles, tentatively identified as lysosomes, and in the bile canalicular lumen. Analysis of cells and media by t.l.c. revealed the slow formation of at least two metabolites. After intravenous injection into bile fistula rats of [9,10-3H-oleoyl]N-Rh-PE incorporated in small unilamellar liposomes, the initial rates of elimination from plasma of 3H and rhodamine label were virtually identical. However, biliary secretion of the 3H label (5.5% of dose at 2 h) was much slower than that of the rhodamine label (49.3% at 2 h). The rhodamine label in bile was chloroform-soluble, but not identical to the native molecule, and was resistant to phospholipase A2 and alkaline hydrolysis. To gain insight in the mechanism of the rapid bile secretion of this metabolite, we compared the processing of N-Rh-PE, its deacylated form [glycerophospho(N sulphorhodamine B sulphonyl)ethanolamine; Gly-N-Rh] and the rhodamine label itself (sulphorhodamine B sulphonyl chloride; SRho). Intravenous injection of chloroform-soluble N-Rh-PE and of methanol/water-soluble Gly-N-Rh complexed with albumin both resulted in rapid bile secretion of chloroform-soluble fluorescent compounds (60.2% and 86.3% respectively at 2 h), which showed behaviour identical to that of the metabolite of liposomal N-Rh-PE on t.l.c. Methanol/water-soluble SRho was also rapidly secreted into bile (89.5% at 2 h) without being metabolized. Bile secretion of the chloroform-soluble metabolite of N-Rh-PE and of SRho was markedly impaired (-31% and -52% respectively) in GY Wistar rats, which express a genetic defect in the hepatobiliary transport of organic anions. Our data show that the rat hepatocyte is capable of modifying the structure of N Rh-PE, a process which proceeds considerably faster in vivo than in vitro. The chloroform-soluble metabolite is subsequently rapidly removed via the bile. The canalicular organic anion transporting system, which is deficient in GY rats, appears to be involved in the excretion of this apolar product of hepatic metabolism. PMID- 1599405 TI - A biochemical analysis of human periodontal tissue proteoglycans. AB - Proteoglycans synthesized by periodontal (gingival, periodontal ligament, dental follicle) fibroblasts were analysed by SDS/polyacrylamide and agarose gel electrophoresis after being labelled with radioactive sulphate. Medium, cell membrane and extracellular matrix fractions were analysed separately. Samples were treated with chondroitinase AC, chondroitinase ABC, heparitinase or a combination of chondroitinase ABC and heparitinase before electrophoretic separation of proteoglycans. Antibodies to versican and decorin were used to identify these molecules by Western immunoblots. For steady-state metabolic radiolabelling of fibroblasts, medium and cell membrane fractions contained about equal proportions of radiolabelled proteoglycans (about 43%), whereas less radioactivity (about 14%) was found in proteoglycans of the matrix fraction. Periodontal fibroblasts produce six major proteoglycans: versican, a high molecular-mass chondroitin sulphate proteoglycan (CSPG); decorin, a dermatan sulphate proteoglycan (DSPG); a membrane-associated heparan sulphate proteoglycan (HSPG); two medium- or matrix-associated HSPGs; and a 91 kDa membrane-associated CSPG. Variation in decorin molecular size was observed in mass cultures of fibroblasts. Similar polydispersity in molecular size of decorin was seen in several clones established from one mass culture. PMID- 1599406 TI - Kinetic resolution of the separate GLUT1 and GLUT4 glucose transport activities in 3T3-L1 cells. AB - A bis-mannose-photolabel-displacement method has been developed for resolving the separate kinetic properties of the glucose transporters GLUT1 and GLUT4, which are both present in 3T3-L1 cells. We have quantified the cell-surface transporter abundance (Bmax.) for the two isoforms by displacing radiolabelled 2-N-[4-(1-azi 2,2,2-trifluoroethyl)benzoyl]-1,3-bis-(D- mannos-4-yloxy)-2-propylamine (ATB BMPA) by non-labelled ATB-BMPA. In cells acutely treated with insulin, the GLUT1 Bmax. was 0.19 microM and the GLUT4 Bmax. was 0.17 microM. In cells which were chronically treated with insulin, the GLUT1 Bmax. was increased by approximately 4-fold to 0.7 microM, whereas the GLUT4 was decreased by approximately 50% (Bmax. = 0.1 microM). However, this large increase in total concentrations of cell surface transporters (the sum of GLUT1 and GLUT4 concentrations) was not reflected in a large increase in 3-O-methyl-D-glucose transport, suggesting that GLUT1 makes a smaller contribution to transport than does GLUT4. In acutely insulin-treated cells at 37 degrees C, the apparent kinetic parameters for 3-O methyl-D-glucose transport were Vapp.max. = 0.52 mM.s-1 and Kapp.m = 12.3 mM. In chronically insulin-treated cells the Vapp.max. = 1.24 mM.s-1 and Kapp.m = 23.0 mM. We have measured the displacement of ATB-BMPA by different concentrations of 3-O-methyl-D-glucose to resolve the separate affinity constants of GLUT1 and GLUT4 for this transported ligand. In acute- and chronic-insulin-treated cells the GLUT1 Km for 3-O-methyl-D-glucose was approximately 20 mM, and the GLUT4 Km for 3-O-methyl-D-glucose was approximately 7 mM. An analysis of these data and the 3-O-methyl-D-glucose transport rates was carried out to calculate transport capacity (TK values) for the two isoforms at 37 degrees C. In acute- and chronic insulin-treated cells the TK values were 0.36 x 10(4) mM-1.min-1 for GLUT1 and 1.13 x 10(4) mM-1.min-1 for GLUT4. Thus GLUT1 has an approximately 3-fold lower transport capacity than GLUT4 at low concentrations of transported sugar. The lower GLUT1 transport capacity was shown to be mainly due to the high Km of GLUT1. The calculated turnover numbers were 7.2 x 10(4) min-1 for GLUT1 and 7.9 x 10(4) min-1 for GLUT4. PMID- 1599407 TI - Subcellular distribution and characteristics of ciprofibroyl-CoA synthetase in rat liver. Its possible identity with long-chain acyl-CoA synthetase. AB - The subcellular distribution and characteristics of ciprofibroyl-CoA synthetase were studied in rat liver and compared with those of long-chain acyl-CoA synthetase (palmitate as substrate) which, as already known, is distributed among mitochondria, microsomes and peroxisomes. Upon differential centrifugation, the subcellular distribution of ciprofibroyl-CoA synthetase followed closely that of palmitoyl-CoA synthetase and was specifically inactivated in the mitochondrial fraction by freezing and thawing, a behaviour already described for palmitoyl-CoA synthetase. Both enzyme activities were found to co-purify through several steps from rat liver microsomes. By using a partially purified enzyme, the activation of ciprofibrate to its acyl-CoA ester followed Michaelis-Menten kinetics with an apparent Km of 0.63 +/- 0.1 mM. Ciprofibroyl-CoA synthetase was competitively inhibited by 25 and 50 microM-palmitic acid. Higher concentrations of the fatty acid resulted in a mixed type of inhibition. Conversely, ciprofibrate up to 0.5 mM was found to inhibit competitively palmitoyl-CoA synthetase, whereas higher concentrations also resulted in a mixed inhibition. The highest activity of ciprofibroyl-CoA synthetase was found in fat and liver homogenates. The distribution of the enzyme in different rat tissues was similar to that of palmitoyl-CoA synthetase. The present results suggest that long-chain acyl-CoA synthetase and ciprofibroyl-CoA synthetase activities reside in identical or closely related proteins. PMID- 1599409 TI - Mechanism of action of purpuromycin. AB - Purpuromycin, an antibiotic active against both fungi and bacteria, shows different modes of action against these two kinds of micro-organisms; in Candida albicans it inhibits RNA synthesis, whereas in Bacillus subtilis protein synthesis is primarily affected, with DNA and RNA synthesis blocked at higher concentrations of the drug. In bacterial cell-free protein-synthesis systems, purpuromycin did not inhibit synthesis from endogenous mRNA (elongation of peptides initiated within the intact cell) but inhibited MS2-phase RNA-dependent protein synthesis (which requires initiation) by 50% at 0.1 mg/l. Poly(U) directed polyphenylalanine synthesis was 50% inhibited by 20 mg of purpuromycin/l when added to a complete system; however, when purpuromycin was preincubated with ribosomes dissociated into 30 S and 50 S subunits, the concentration for 50% inhibition fell to 0.1 mg/l. By contrast, in a C. albicans cell-free system poly(U)-directed polyphenylalanine synthesis was partially inhibited only at 200 mg/l. Purpuromycin also inhibited polynucleotide synthesis in vitro in reactions using Escherichia coli or wheat-germ RNA polymerases or E. coli DNA polymerase I. We suggest that in bacteria the primary target of purpuromycin is on ribosomes and that its action precedes the elongation step of protein synthesis. The effect on nucleic acid synthesis in both fungi and bacteria may be due to interaction of purpuromycin with DNA. PMID- 1599408 TI - Hypolipidaemic drugs are activated to acyl-CoA esters in isolated rat hepatocytes. Detection of drug activation by human liver homogenates and by human platelets. AB - The formation of acyl-CoA esters of the hypolipidaemic peroxisome proliferators clofibric acid, ciprofibrate and nafenopin was studied in isolated rat hepatocytes. The concentration of ciprofibroyl-CoA in the liver of ciprofibrate treated rats was in the range of 10-30 microM. The three drugs formed acyl-CoA esters when incubated with isolated hepatocytes. Their formation was saturable and reached a plateau after 30 min incubation. Maximal intracellular concentrations of ciprofibroyl-CoA and clofibroyl-CoA (100 microM and 55 microM respectively) were attained at 0.5 mM of the free drugs in the incubation medium, whereas for nafenopin-CoA, the maximal intracellular concentration (9 microM) was reached at 1 mM-nafenopin. At low concentrations of the hypolipidaemic compounds in the incubation medium a significant proportion of the total intracellular drug was present as its acyl-CoA ester (25-35% for ciprofibrate). When isolated hepatocytes were incubated with a ciprofibrate concentration comparable with that observed in the blood of drug-treated rats (0.1 mM), ciprofibroyl-CoA attained an intracellular concentration similar to that previously observed in the liver of treated rats. The formation of ciprofibroyl-CoA by isolated rat hepatocytes was stimulated by the addition of carnitine and partially inhibited by the addition of palmitate. Further, it was shown that human liver homogenates synthesized ciprofibroyl-CoA at a rate similar to that observed for rat liver homogenates. Solubilized human platelets also formed ciprofibroyl-CoA, although at a rate two orders of magnitude lower than that of liver. The results support the view that acyl-CoA esters of hypolipidaemic peroxisome proliferators may be the pharmacologically active species of the drugs. PMID- 1599411 TI - ATP-dependent bile-salt transport in canalicular rat liver plasma-membrane vesicles. AB - The present study identifies and characterizes a novel ATP-dependent bile-salt transport system in isolated canalicular rat liver plasma-membrane (cLPM) vesicles. ATP (1-5 mM) stimulated taurocholate uptake into cLPM vesicles between 6- and 8-fold above equilibrium uptake values (overshoot) and above values for incubations in the absence of ATP. The ATP-dependent portion of taurocholate uptake was 2-fold higher in the presence of equilibrated KNO3 as compared with potassium gluconate, indicating that the stimulatory effect of ATP was not due to the generation of an intravesicular positive membrane potential. Saturation kinetics revealed a very high affinity (Km approximately 2.1 microM) of the system for taurocholate. The system could only minimally be stimulated by nucleotides other than ATP. Furthermore, it was preferentially inhibited by conjugated univalent bile salts. Further strong inhibitory effects were observed with valinomycin, oligomycin, 4,4'-di-isothiocyano-2,2'-stilbene disulphonate, sulphobromophthalein, leukotriene C4 and N-ethylmaleimide, whereas nigericin, vanadate, GSH, GSSG and daunomycin exerted only weak inhibitory effects or none at all. These results indicate the presence of a high-affinity primary ATP dependent bile-salt transport system in cLPM vesicles. This transport system might be regulated in vivo by the number of carriers present at the perspective transport site(s), which, in addition to the canalicular membrane, might also include pericanalicular membrane vesicles. PMID- 1599410 TI - Secretion of a functional soluble form of neutral endopeptidase-24.11 from a baculovirus-infected insect cell line. AB - Neutral endopeptidase (NEP; EC 3.4.24.11) is an integral membrane protein found at the plasma membrane of many cell types. A secreted form of NEP (sec-NEP) was recently obtained by transfection of COS-1 cells with a recombinant expression vector consisting of the cDNA encoding the signal peptide of pro-opiomelanocortin fused in-frame to the cDNA sequence of the complete ectodomain of rabbit NEP [Lemay, Waksman, Roques, Crine & Boileau (1989) J. Biol. Chem. 264, 15620-15623]. In order to produce large quantities of this enzyme for structural studies we have expressed this recombinant soluble form of NEP at high yields using a baculovirus/insect-cell system. A recombinant Autographa californica nuclear polyhedrosis-virus genome containing the sec-NEP sequence was used to infect host Spodoptera frugiperda Sf9 cells. Infected cells secreted an N-glycosylated soluble form of neutral endopeptidase which was enzymically active. The yield was about 80 nmol of enzyme/litre of culture. The soluble form of the recombinant enzyme purified by immunoaffinity showed the same catalytic properties as the wild-type enzyme extracted from the kidney brush-border membranes. Treatment of the recombinant enzyme with endo-beta-N-acetylglucosaminidase H showed, however, that invertebrate cells did not glycosylate the enzyme to the same extent as did mammalian cells. Our findings demonstrate that insect cells can be used as hosts for the production of the soluble form of neutral endopeptidase. We also conclude that neither a full complement of carbohydrate side chains nor the membrane anchor appear to be essential for the production and targeting to the cell surface of a fully functional enzyme in this expression system. PMID- 1599412 TI - Localization of a myosin subfragment-1 interaction site on the C-terminal part of actin. AB - The actin-myosin head complex in the rigor state reveals several high-affinity sites on the actin molecule in sequences 18-28 and 40-113. In the presence of Mg(2+)-ATP, participation of the actin N-terminal 1-7 sequence is known to occur. The proximity of the C-terminal region of actin to the A1 light chain of the myosin head [S-1(A1)] (where S-1 is myosin subfragment-1) was described previously. We observed that C-terminal antigenic structures located near Met 305, Met-325 and Met-355 and the C-terminal end (Cys-374) of actin are markedly modified in the presence of S-1(A1), S-1(A2) and scallop S-1 and in the absence of Mg(2+)-ATP. This seems to rule out any important specific involvement of the A1 light chain in the described conformational changes. An S-1-binding site was located in this actin C-terminal region by testing the tryptic CB9 peptide (360 372 sequence) previously implicated in the A1 light chain interaction. This peptide was able to bind well to S-1(A1), S-1(A2) and scallop S-1, but not in the presence of Mg(2+)-pyrophosphate. These results strengthen the hypothesis of a multisite interface between S-1 and actin located in the actin subdomain I. PMID- 1599414 TI - Primary structure of a Thomsen-Friedenreich-antigen-specific lectin, jacalin [Artocarpus integrifolia (jack fruit) agglutinin]. Evidence for the presence of an internal repeat. AB - Jacalin [Artocarpus integrifolia (jack fruit) agglutinin] is made up of two types of chains, heavy and light, with M(r) values of 16,200 +/- 1200 and 2090 +/- 300 respectively (on the basis of gel-permeation chromatography under denaturing conditions). Its complete amino acid sequence was determined by manual degradation using a 4-dimethylaminoazobenzene 4'-isothiocyanate double-coupling method. Peptide fragments for sequence analysis were obtained by chemical cleavages of the heavy chain with CNBr, hydroxylamine hydrochloride and iodosobenzoic acid and enzymic cleavage with Staphylococcus aureus proteinase. The peptides were purified by a combination gel-permeation and reverse-phase chromatography. The light chains, being only 20 residues long, could be sequenced without fragmentation. Amino acid analyses and carboxypeptidase-Y-digestion C terminal analyses of the subunits provided supportive evidence for their sequence. Computer-assisted alignment of the jacalin heavy-chain sequence failed to show sequence similarity to that of any lectin for which the complete sequence is known. Analyses of the sequence showed the presence of an internal repeat spanning residues 7-64 and 76-130. The internal repeat was found to be statistically significant. PMID- 1599413 TI - Effect of desialylation on the biological properties of human plasminogen. AB - There are two major isoenzymes of plasminogen (Pg) in human plasma, designated Pg1 and Pg2. Both Pg forms have an identical primary structure, but differ in their extent of glycosylation. Removal of the oligosaccharide chains alters the normal physiological function of the zymogen and decreases the circulation time of both Pg glycoforms. Recent studies in our laboratory demonstrated that Pg2, with one carbohydrate chain, binds to the surface of U937 monocytoid cells considerably better than Pg1, with two carbohydrate chains, indicating a major role for the carbohydrate chains as determinants for differential binding to the cell surface [Gonzalez-Gronow, Grenett, Fuller & Pizzo (1990) Biochim. Biophys. Acta 1039, 269-276]. In this report we provide evidence that removal of terminal sialic acid from the Thr345-linked oligosaccharide chain of Pg2 is accompanied by the appearance of spontaneous amidolytic and fibrinolytic activity in the single chain zymogen. Kinetic data demonstrate that asialo-Pg hydrolyses peptide substrates approximately 10% as efficiently as Pm. In addition, the change in carbohydrate content also alters Pg binding to U937 cells. Asialo-Pg binds to U937 cells with a decreased capacity but with a greater affinity than native Pg. Furthermore, asialo-Pg does not compete with native Pg for cell binding. These studies directly demonstrate that the oligosaccharide chains contribute to the heterogeneity observed in the physicochemical and biological properties of Pg1 and Pg2. PMID- 1599415 TI - Cloning and heterologous expression of cDNA encoding class alpha rat glutathione transferase 8-8, an enzyme with high catalytic activity towards genotoxic alpha,beta-unsaturated carbonyl compounds. AB - A cDNA clone, lambda GTRA8, encoding rat glutathione transferase subunit 8 has been isolated from a lambda gt10 rat hepatoma cDNA library. The previously known amino acid sequence of the enzyme was used to design primers for a polymerase chain reaction that yielded a 0.3 kb DNA fragment from the hepatoma library. The 0.3 kb fragment was used as a probe for screening and a 0.9 kb cDNA clone containing a complete open reading frame was obtained. After DNA sequencing and subcloning into an expression vector, the enzyme was expressed in Escherichia coli and purified. Specific activities and kcat./Km values were determined for a number of substrates, including alpha,beta-unsaturated carbonyl compounds. The highest activity was obtained with 4-hydroxyalkenals and with acrolein, genotoxic products of lipid peroxidation. In addition, the rat class Alpha glutathione transferase 8-8 displays high catalytic activity in the reaction between glutathione and the diuretic drug ethacrynic acid, a compound normally considered as a substrate characteristic for class Pi glutathione transferases. PMID- 1599417 TI - Pyridoxal arsenate as a prosthetic group for aspartate aminotransferase. AB - The apoenzyme of aspartate aminotransferase formed a stable, active holoenzyme on treatment with pyridoxal in the presence of arsenate. PMID- 1599416 TI - Exocytosis from permeabilized bovine adrenal chromaffin cells is differently modulated by guanosine 5'-[gamma-thio]triphosphate and guanosine 5'-[beta gamma imido]triphosphate. Evidence for the involvement of various guanine nucleotide binding proteins. AB - 1. In bovine adrenal chromaffin cells made permeable either to molecules less than or equal to 3 kDa with alphatoxin or to proteins less than or equal to 150 kDa with streptolysin O, the GTP analogues guanosine 5'-[beta gamma imido]triphosphate (p[NH]ppG) and guanosine 5'-[gamma-thio]triphosphate (GTP[S]) differently modulated Ca(2+)-stimulated exocytosis. 2. In alphatoxin permeabilized cells, p[NH]ppG up to 20 microM activated Ca(2+)-stimulated exocytosis. Higher concentrations had little or no effect. At a free Ca2+ concentration of 5 microM, 7 microM-p[NH]ppG stimulated exocytosis 6-fold. Increasing the free Ca2+ concentration reduced the effect of p[NH]ppG. Pretreatment of the cells with pertussis toxin prevented the activation of the Ca(2+)-stimulated exocytosis by p[NH]ppG. 3. In streptolysin O-permeabilized cells, p[NH]ppG did not activate, but rather inhibited Ca(2+)-dependent catecholamine release under all conditions studied. In the soluble cytoplasmic material that escaped during permeabilization with streptolysin O, different G protein alpha-subunits were detected using an appropriate antibody. Around 15% of the cellular alpha-subunits were detected in the supernatant of permeabilized control cells. p[NH]ppG or GTP[S] stimulated the release of alpha-subunits 2 fold, causing a loss of about 30% of the cellular G-protein alpha-subunits under these conditions. Two of the alpha-subunits in the supernatant belonged to the G(o) type, as revealed by an antibody specific for G(o) alpha. 4. GTP[S], when present alone during stimulation with Ca2+, activated exocytosis in a similar manner to p[NH]ppG. Upon prolonged incubation, GTP[S], in contrast to p[NH]ppG, inhibited Ca(2+)-induced exocytosis from cells permeabilized by either of the pore-forming toxins. This effect was resistant to pertussin toxin. 5. The p[NH]ppG-induced activation of Ca(2+)-stimulated release from alphatoxin permeabilized chromaffin cells may be attributed to one of the heterotrimeric G proteins lost during permeabilization with streptolysin O. The inhibitory effect of GTP[S] on exocytosis is apparently not mediated by G-protein alpha-subunits, but by another GTP-dependent process still occurring after permeabilization with streptolysin O. PMID- 1599418 TI - Testing and characterizing enzymes and membrane-bound carrier proteins acting on amphipathic ligands in the presence of bilayer membrane material and soluble binding protein. Application to the uptake of oleate into isolated cells. AB - 1. A multiphasic modelling approach [Heirwegh, Meuwissen, Vermeir & De Smedt (1988) Biochem. J. 254, 101-108] is applied to systems containing poorly water soluble amphipathic reactants, membrane material, soluble binding protein and acceptor protein (enzyme or membrane-bound carrier protein). 2. The field of application is constrained by the assumptions (i) that the amount of acceptor bound substrate is small compared with the total amount and (ii) that all preceding chemical reactions and steps of mass transport are rapid compared with the chemical change monitored. 3. Initial-rate formulae for systems in which an acceptor interacts with unbound or protein-bound ligand are given. The saturation curves are near-hyperbolic or sigmoidal, depending both (i) on the form of ligand (unbound or protein-bound) acted upon by the acceptor and (ii) on whether the assays are performed at constant concentration of soluble binding protein Cp or at constant substrate/binding-site molar ratio RS. 4. Several diagnostic features permit unequivocal distinction between acceptor action on unbound or protein bound substrate. In the former case, saturation curves, run at the same constant concentration of one of several binding proteins of increasing binding affinity, will show progressively increasing inhibition, the shape changing from near hyperbolic at Km' less than K1' to sigmoidal at Km' greater than K1'.Km' is the effective Michaelis constant of the acceptor and K1' the effective dissociation constant of the binding sites of the soluble protein (for the sites with the higher binding affinity, if several classes of binding site are present on the protein). Alternatively, the maximum velocity obtained at constant RS less than or equal to 1 should increase hyperbolically with RS/(1-RS) for a binding protein with a single class of binding site. The formula that applies when the binding protein contains two classes of independent binding site is also available. When the acceptor acts on protein-bound ligand, the maximum velocity obtained at constant binding-protein concentration, Cp, increases hyperbolically with Cp. 5. Application of these and additional criteria to initial-rate data on the uptake of oleate into isolated cells supports a mechanism of carrier-mediated uptake of the unbound ligand and allows one to clarify some observations that hitherto had been poorly explained. 6. The influence of soluble binding protein on the reaction and substrate specificities of ligand/acceptor interaction is also discussed. 7. In its present state, data treatment for 'double binding-protein systems' generally requires separate determination of the binding parameters of the soluble binding protein.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599419 TI - Fructose metabolism in the human erythrocyte. Phosphorylation to fructose 3 phosphate. AB - In human erythrocytes, the first step in the metabolism of fructose is generally thought to be phosphorylation to fructose 6-phosphate catalysed by hexokinase. In variance with this assumption, we show here that fructose in these cells is metabolized primarily to fructose 3-phosphate by a specific 3-phosphokinase. This process has an overall estimated Km of 30 mM with respect to extracellular fructose and an apparent Vmax. of 0.6 mumol/h per ml. At a fixed concentration of fructose in the medium, the accumulation of fructose 3-phosphate was linearly dependent on the duration of incubation up to 5 h and was not affected by glucose. Once accumulated, fructose 3-phosphate appears to be degraded and/or relatively slowly metabolized, decreasing by only approximately 30% after a 12 h incubation in a fructose-free medium. PMID- 1599420 TI - Quantification of contributions of phospholipid precursors to diradylglycerols in stimulated mononuclear phagocytes. AB - Phosphatidylcholine (PC) hydrolysis has been shown to occur in hormone-stimulated cells and represents a potential metabolic source, in addition to phosphoinositides, for the generation of diradylglycerols (DG). We performed studies in order to quantify the importance of this pathway in DG formation. We incubated murine peritoneal macrophages with platelet-activating factor (PAF), ionomycin, phorbol myristate acetate (PMA) or no stimulus in a series of timed incubations ranging from 15 s to 20 min. We quantified the profiles of the molecular species in the accumulated DG after extraction, specific radiolabelling to give [32P]phosphatidic acid by DG kinase, and conversion to the dimethyl derivative. We used two independent methods for molecular species analysis: (1) reversed-phase h.p.l.c. separation with in-line beta-radiation detection of peaks, and (2) an argentation-t.l.c. separation with scintillation counting of bands. Our results showed a clearly biphasic sequence in the composition of accumulated DG. The molecular species composition of early DG (up to 1 min stimulation time) was very similar to that of unstimulated DG, whereas the proportions of the species present in later DG were substantially altered. In the same experiments, we extracted native phospholipids from unstimulated macrophages, separated phosphatidylinositol (PI), PC, phosphatidylethanolamine (PE) and phosphatidylserine (PS), converted them to the corresponding DGs by using phospholipase C, and determined their molecular species compositions as above. In comparison with the diradyl compositions of stimulated DG, the diradyl composition of PI closely matched that of early DG, the differences between the PC and PI compositions matched the differences between early and late DG very closely, and the compositions of PE and PS were unique and unrelated. We quantified these relationships more precisely by multilinear regression analysis to calculate the theoretical best mix of five molecular species compositions (PI, PC, PE, PS and unstimulated DG) that would most closely replicate the early and late accumulated DG compositions. We found that by both h.p.l.c. and t.l.c. analyses, 15-30% (PAF) or 25-50% (ionomycin and PMA) of the later DG could be accounted for by PC hydrolysis. These results represent quantifications of phospholipid class contributions to stimulated DG formation, and demonstrate the potential importance of PC hydrolysis in phagocytic leucocytes. PMID- 1599421 TI - Purification and N-terminal sequencing of peptidyl-prolyl cis-trans-isomerase from rat liver mitochondrial matrix reveals the existence of a distinct mitochondrial cyclophilin. AB - 1. Rat liver mitochondrial matrix peptidyl-prolyl cis-trans-isomerase (PPIase) has been purified. The major form of the enzyme has a molecular mass of 18.6 kDa, with a minor active component of 17.6 kDa. 2. The second-order rate constant for cyclosporin A binding to the enzyme was determined from the time-dependence of the inhibition of PPIase by low concentrations of cyclosporin A and found to be 0.9 microM-1.s-1 at 10 degrees C. 3. The Ki for cyclosporin A inhibition of the enzyme was 3.6 nM, and the half-life for dissociation of the enzyme-inhibitor complex was 3.6 min. 4. From the specific activity of the pure enzyme it can be calculated that isolated liver mitochondria contain approx. 45 pmol of enzyme per mg of total mitochondrial protein. Higher values estimated previously [Halestrap & Davidson (1990) Biochem. J. 268, 153-160] are explained by the use of a short (30 s) preincubation period of the enzyme with cyclosporin, which is insufficient to allow full equilibration of the binding of the inhibitor to the PPIase. 5. N Terminal sequencing of the 18.6 and 17.5 kDa forms of PPIase show the presence of mitochondrial presequences of 13 and three amino acids respectively, with the remaining sequence having a strong sequence similarity to other cyclophilins. 6. Parallel purification and N-terminal sequencing of rat cytosolic PPIase showed the two proteins to have significant differences, implying that they are probably products of separate genes. PMID- 1599422 TI - Macrophage activation for intracellular killing as induced by a Ca2+ ionophore. Dependence on L-arginine-derived nitrogen oxidation products. AB - Mouse macrophages activated by interferon-gamma kill intracellular Leishmania by a process that depends on the generation of L-arginine-derived nitrogen oxidation products. Interferon-induced intracellular killing can be mimicked by exposure of macrophages to the Ca2+ ionophore A23187 in the presence of lipopolysaccharide. The mechanisms of this effect were therefore investigated. Destruction of the parasite was accompanied by accumulation of nitrite in the macrophage culture fluids. Leishmanicidal activity and nitrite production in cultures stimulated with ionophore A23187 and lipopolysaccharide were abrogated when cells were activated in medium containing arginase or the L-arginine analogues L-canavanine, guanidine or NG-monomethyl-L-arginine. L-Arginine was required during the lipopolysaccharide-induced triggering phase only. Indeed, macrophage priming with ionophore A23187 in L-arginine-depleted medium led to full microbicidal activity and nitrite generation provided that L-arginine was present during subsequent triggering by lipopolysaccharide. Addition of NG-monomethyl-L-arginine to ionophore-activated macrophages increased O2- production on phorbol myristate stimulation, while inhibiting glucose oxidation through the hexose monophosphate shunt pathway. Leishmanicidal activity and nitrite production were also inhibited when ionophore-treated cultures were incubated with excess iron, implying a role for iron as a defence mechanism against the toxicity of nitrogen derivatives. These results indicate that the ionophore-induced leishmanicidal activity occurs through a process similar to that evoked by interferon-gamma, i.e. the production of L-arginine-derived nitrogen oxidation products. PMID- 1599423 TI - Induction and degradation of the uncoupling protein thermogenin in brown adipocytes in vitro and in vivo. Evidence for a rapidly degradable pool. AB - The induction and degradation of the brown-fat-specific uncoupling protein thermogenin in brown fat cell cultures was investigated. Cultures were initiated with undifferentiated precursor cells from young mice and the amount of thermogenin was determined by immunoblotting. High levels of thermogenin could be induced by noradrenaline treatment in cells grown for more than 5 days in culture, and in such cell cultures continuously stimulated with noradrenaline, the thermogenin level continued to increase for at least a further 5 days. In cell cultures stimulated for only 24 h, the induced thermogenin was subsequently specifically and rapidly degraded, with a half-life of 20 h. As the half-life was prolonged by cycloheximide treatment, the degradation was apparently due to the induction of specific proteins after cessation of adrenergic stimulation. In cell cultures continuously stimulated with noradrenaline for 5 days, the induced thermogenin was degraded much more slowly after noradrenaline removal, with a half-life of 70 h. This half-life was unchanged by cycloheximide treatment, and the degradation after cycloheximide was in parallel with the degradation of protein in general, and was therefore non-specific. The prolongation of the half life of thermogenin after the chronic treatment may be related to mitochondrial incorporation of thermogenin and consequent stabilization of the protein. The half-life of thermogenin in an in vivo situation of similar experimental design (the reacclimation of mice to warm after 5 days in the cold), was also long (about 7 days), and the loss was also non-specific, as it paralleled the loss of protein. Thus different molecular events are involved in thermogenin degradation when the protein is found in different functional pools. PMID- 1599424 TI - Purification of PKC-I, an endogenous protein kinase C inhibitor, and types II and III protein kinase C isoenzymes from human neutrophils. AB - Human neutrophil protein kinase C (PKC) activity is inhibited by an endogenous protein found primarily in the pellet fraction from homogenized specific granules, which was both heat- and proteinase-sensitive [Balazovich, Smolen & Boxer (1986) J. Immunol. 137, 1665-1673]. We now report that two PKC isoenzymes and the endogenous PKC inhibitor, which we named PKC-I, were purified from human neutrophils. A neutrophil soluble fraction that was subjected to DEAE-Sephacel chromatography yielded highly enriched PKC because, by definition, enzymic activity was strictly dependent on Ca2+ and phosphatidylserine. Hydroxyapatite chromatography resolved two peaks of PKC activity. Type II and Type III PKC isoenzymes were each identified on Western blots by using isoenzyme-specific monoclonal antibodies. Unlike rat brain, from which PKC isoenzymes were also purified, Type I PKC was not detected in human neutrophils. Western blots indicated that both Type II and Type III PKC isoenzymes had molecular masses near 80 kDa. In agreement with other reports, PKC was autophosphorylated in vitro. PKC I, an endogenous neutrophil inhibitor of PKC, was purified to apparent homogeneity by DEAE-Sephacel and S-400 Sephacel chromatography. PKC-I had a molecular mass of 41 kDa. PKC-I inhibited purified PKC activity stimulated by 1,2 diacylglycerols in a concentration-dependent manner, and inhibited PKC-dependent phosphorylation of proteins present in neutrophil cytosol. PMID- 1599425 TI - Kinetic parameters for the generation of endothelins-1,-2 and -3 by human cathepsin E. AB - The specific conversion of human endothelin (ET) precursors big ET-1, big ET-2 and big ET-3 into their respective ET by cathepsin E was examined. Comparable pH optima were obtained for ET-1 and ET-2 generation, whereas effective conversion of big ET-3 into ET-3 necessitated a lower pH value. Determination of kinetic parameters (Km, kcat.) for all three conversions indicated that the precursors were efficiently bound by cathepsin E. The significance of the values obtained for the catalytic-centre activities and the effect of a specific inhibitor are discussed. PMID- 1599426 TI - Mutations altering substrate specificity in OHIO-1, and SHV-1 family beta lactamase. AB - The OHIO-1 beta-lactamase does not normally hydrolyse oxyimino-beta-lactam substrates like cefotaxime, ceftriaxone, ceftazidime or aztreonam. We were able to select spontaneous mutants of an OHIO-1-bearing strain of Escherichia coli using the antibiotic substrates listed above by enrichment methods of frequencies of 10(-8)-10(-10) for all antibiotics except ceftazidime (frequency less than 10( 10)). Most mutants with increased resistance to the other beta-lactams were also more resistant to ceftazidime. Mutations identified by DNA sequencing included a Gly238----Ser238 substitution identical with the SHV-2 mutation previously described, cysteine and valine substitutions at the identical site, and a Gly242- --Cys242 substitution. The Cys238 and Cys242 mutant enzymes had less affinity for aztreonam than had the other mutant enzymes. Hydrolysis of cefotaxime, but not cephaloridine, by the cysteine-substituted enzymes was inhibited by p chloromercuribenzoate. The mutant enzymes had, in general, greater affinity for the mechanism-based inhibitors sulbactam, clavulanic acid and tazobactam. These results suggest two non-mutually exclusive hypotheses for the structural role of substitutions in this area of the enzyme. Either potential hydrogen-bond donors, such as serine and cysteine, interact directly with the beta-lactam molecules, or the steric bulk of these substitutions distorts the beta-pleated sheet such that the beta-lactam is held in a position favourable for stable binding and catalysis. Finally, our data raise questions about a strategy relying on oligonucleotide-probe technology to detect such mutations, because of the variety of substitutions that give rise to similar phenotypes. PMID- 1599427 TI - Multiplicity of UDP-glucuronosyltransferases in fish. Purification and characterization of a phenol UDP-glucuronosyltransferase from the liver of a marine teleost, Pleuronectes platessa. AB - The aim of this work was to determine if a non-mammalian species had multiple UDP glucuronosyltransferase (UDPGT) isoforms. At least six highly purified UDPGT isoenzymes were partially resolved by anion-exchange chromatography and UDP hexanolamine-Sepharose 4B affinity chromatography from liver microsomes of a fish, the plaice. Q-Sepharose FF, chromatofocusing and affinity-chromatographic procedures were employed to separate and purify the phenol UDPGT isoform to apparent homogeneity. The purified enzyme conjugated 1-naphthol, but not bilirubin or steroids, and displayed a pI of 7.0 and a subunit molecular mass of 55 kDa. Bilirubin and testosterone UDPGT activities were more labile and, although purified over 200-fold, these preparations also contained the phenol UDPGT and had multiple polypeptides with molecular masses of 52-57 kDa. Antisera to rat bilirubin/phenol UDPGT and testosterone/phenol UDPGT isoforms cross reacted strongly with the partially purified plaice UDPGT isoforms of molecular masses 52, 53 and 57 kDa and less strongly with phenol UDPGT 54 kDa and 56 kDa isoforms. Fish and mammalian UDPGTs therefore apparently possess a high degree of evolutionary conservation. PMID- 1599428 TI - Histamine H1-receptor-mediated calcium influx in DDT1MF-2 cells. AB - Undifferentiated monolayers of the hamster vas deferens smooth-muscle cell line, DDT1MF-2, were grown on glass coverslips and loaded with the Ca(2+)-sensitive fluorescent dye fura-2. Stimulation with histamine produced a rapid and maintained increase in intracellular free Ca2+ ([Ca2+]i), with an EC50 of 7.0 +/- 0.7 microM. The initial rise in [Ca2+]i can be attributed to Ca2+ release from intracellular stores, whereas the maintained or plateau phase is due to influx of extracellular Ca2+. The Ca2+ influx associated with the plateau phase required the continued presence of histamine on the receptor, since the H1-antagonist mepyramine (10 microM) attenuated the rise in [Ca2+]i observed when extracellular Ca2+ was re-applied after the cells had been stimulated with histamine, in experiments performed in nominally Ca(2+)-free buffer. Pretreatment with the inorganic Ca(2+)-channel blockers Ni2+ (1 mM) and Co2+ (1 mM) inhibited the influx component, whereas the organic voltage-operated Ca(2+)-channel antagonists nifedipine (10 microM) and PN-200-110 (10 microM) had no effect. These data suggest that histamine stimulates Ca2+ influx through an H1-receptor-activated Ca2+ channel. Experiments with Mn2+ indicated that the receptor-mediated Ca(2+) influx pathway(s) is impermeable to Mn2+. Furthermore, the refilling of Ca2+ stores can occur independently of H1-receptor-mediated influx, since store refilling can be demonstrated even when the receptor-mediated Ca2+ entry is blocked by mepyramine. In conclusion, H1-receptor activation in the smooth-muscle cell line DDT1MF-2 stimulates both release of Ca2+ from intracellular stores [inositol 1,4,5-triphosphate (InsP3)-mediated] and Ca2+ influx through a receptor activated Ca2+ channel. The subsequent refilling of the InsP3-sensitive intracellular Ca2+ store is independent of histamine H1-receptor stimulation (mepyramine-insensitive) and occurs without an observable rise in cytosolic free Ca2+. PMID- 1599429 TI - Identification of the 52 kDa cytoskeletal-like protein of cytochalasin D stimulated normal rat kidney (NRK/CD) cells as substrate-associated glycoprotein p52 [plasminogen-activator inhibitor type-1 (PAI-1)]. Expression of p52 (PAI-1) in NRK/CD cells is regulated at the level of mRNA abundance. AB - Cell shape profoundly affects cellular metabolic activity, protein and nucleic acid synthesis, and cytoskeletal organization. To examine the influence of cell shape on protein expression, normal rat kidney (NRK) cells were exposed to the microfilament-disrupting drug cytochalasin D (CD), labelled with [35S]methionine, and newly synthesized cellular and cytoskeletal proteins examined by two dimensional gel electrophoresis. CD produced dramatic changes in cell shape (from a flat to round phenotype) with concomitant 3-7-fold increases in the cellular content and cytoskeletal deposition of the microfilament-associated proteins actin, alpha-actinin, and tropomyosin isoform 1. Augmented actin protein content in NRK/CD cells was paralleled by a corresponding increase in actin mRNA abundance and was inhibited by prior addition of actinomycin D. A detergent insoluble protein of 52 kDa was also detected at high levels in the cytoskeletal fraction of NRK/CD cells. Two-dimensional electrophoretic mapping of total cellular and cytoskeletal proteins revealed this 52 kDa protein to be the previously described glycoprotein p52 [Higgins & Ryan (1989) Biochem. J. 257, 173 182]. By using electrophoretic and immunochemical criteria, p52 was identified as plasminogen-activator inhibitor type-1 (PAI-1). Like actin, CD-induced p52(PAI-1) synthesis, cellular content, and partitioning to the detergent-insoluble cytoskeletal compartment reflected a corresponding increase in p52(PAI-1) mRNA. Such induction was similarly inhibited by actinomycin D. p52(PAI-1) expression in the NRK-cell system is thus responsive to CD-mediated shape changes and requires ongoing RNA synthesis for its induction. Differential extraction of detached cell bodies and the substrate-adherent 'remnant' fraction of NRK/CD cultures, furthermore, indicated that p52(PAI-1) was not an intrinsic internal cytoskeletal element but, rather, selectively localized to the extracellular residue. p52(PAI 1) retained its detergent-insoluble characteristics even in this isolated 'remnant' fraction, where it was also the predominant protein species resolved. PMID- 1599430 TI - Relationships between the degree of cross-linking of surface immunoglobulin and the associated inositol 1,4,5-trisphosphate and Ca2+ signals in human B cells. AB - Cross-linking of surface immunoglobulin (Ig) receptors on human B cells leads to the activation of a tyrosine kinase. The activated tyrosine kinase subsequently phosphorylates a number of substrates, including phospholipase C-gamma. This enzyme breaks down phosphoinositol bisphosphate to form two intracellular messengers, diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C and the release of intracellular Ca2+ respectively. We have used h.p.l.c. and flow cytometry to measure accurately the inositol phosphate turnover and Ca2+ release in anti-Ig-stimulated human B cells. In particular, we have examined the effect of dose of the cross-linking antibody on the two responses. The identity of putative messenger inositol phosphates has been verified by structural analysis, and the amounts of both inositol phosphates and Ca2+ present have been quantified. In the Ramos Burkitt lymphoma, which is very sensitive to stimulus through its Ig receptors, both inositol phosphate production and Ca2+ release were found to be related to the dose of anti-Ig antibody applied. This suggests that phospholipase C-mediated signal transduction in human B cells converts the degree of cross-linking of the immunoglobulin receptor quantitatively into intracellular signals. PMID- 1599431 TI - The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas. AB - In hepatocyte cultures maintained in the absence of extracellular fatty acids, at least 70% of the secreted very-low-density lipoprotein (VLDL) triacylglycerol was derived via lipolysis of intracellular triacylglycerol. This proportion was unchanged when the cells were exposed for 24 h to insulin or glucagon, hormones which decreased the overall secretion of intracellular triacylglycerol, or to chloroquine or tolbutamide, agents which inhibit lysosomal lipolysis. The rate of intracellular lipolysis was 2-3-fold greater than that required to maintain the observed rate of triacylglycerol secretion. Most of the fatty acids released were returned to the intracellular pool. Neither insulin nor glucagon had any significant effect on the overall lipolysis and re-esterification of intracellular triacylglycerol. In these cases a greater proportion of the released fatty acids re-entered the cellular pool, rather than being recruited for VLDL assembly. Tolbutamide inhibited intracellular lipolysis, but suppressed VLDL secretion to a greater extent. 3,5-Dimethylpyrazole did not affect lipolysis or VLDL secretion. The increased secretion of VLDL triacylglycerol observed after exposure of cells to insulin for 3 days was not accompanied by an increased rate of intracellular lipolysis. However, a larger proportion of the triacylglycerol secreted under these conditions may not have undergone prior lipolysis. PMID- 1599432 TI - Human homologues of the bacterial heat-shock protein DnaJ are preferentially expressed in neurons. AB - The bacterial heat-shock protein DnaJ has been implicated in protein folding and protein complex dissociation. The DnaJ protein interacts with the prokaryotic analogue of Hsp70, DnaK, and accelerates the rate of ATP hydrolysis by DnaK. Several yeast homologues of DnaJ, with different proposed subcellular localizations and functions, have recently been isolated and are the only eukaryotic forms of DnaJ so far described. We have isolated cDNAs corresponding to two alternatively spliced transcripts of a novel human gene, HSJ1, which show sequence similarity to the bacterial DnaJ protein and the yeast homologues. The cDNA clones were isolated from a human brain-frontal-cortex expression library screened with a polyclonal antiserum raised to paired-helical-filament (PHF) proteins isolated from extracts of the brains of patients suffering from Alzheimer's disease. The similarity between the predicted human protein sequences and the bacterial and yeast proteins is highest at the N-termini, this region also shows a limited similarity to viral T-antigens and is a possible common motif involved in the interaction with DnaK/Hsp70. Northern-blot analysis has shown that human brain contains higher levels of mRNA for the DnaJ homologue than other tissues examined, and hybridization studies with riboprobes in situ show a restricted pattern of expression of the mRNA within the brain, with neuronal layers giving the strongest signal. These findings suggest that the DnaJ-DnaK (Hsp70) interaction is general to eukaryotes and, indeed, to higher organisms. PMID- 1599433 TI - The isolation and characterization of high-density-lipoprotein subfractions containing apolipoprotein E from human plasma. AB - 1. Plasma high-density lipoprotein (HDL) was separated by heparin-Sepharose affinity chromatography into a non-bound, apolipoprotein E-poor, and a bound, apolipoprotein E-rich, fraction through the binding effect of Mn2+ in the column buffer. 2. The application of a series of elution buffers in which the concentration of Mn2+ was progressively replaced by Mg2+ resulted in the separation of the bound HDL into five subfractions. 3. Each subfraction migrated a different distance on gradient-gel electrophoresis. Three of the subfractions had RF (relative migration compared with BSA) values within the range of HDL2b. One subfraction contained largely HDL2a, with some material in the regions of HDL2b and HDL3a, and one subfraction spanned the RF regions of HDL2a, HDL3a and HDL3b. 4. The number of molecules, per HDL particle, of cholesteryl ester, non esterified cholesterol and phospholipid increased with particle size, whereas triacylglycerol passed through a maximum and the number of amino acid residues remained approximately the same. 5. Apolipoprotein (apo) A-I was the major apoprotein in all five subfractions, but the latter differed appreciably in their contents of apo A-II and apo E. 6. The major fatty acid component of each subfraction was linoleic acid, with moderate amounts of C16:0 and C18:1 fatty acids and a smaller content of C18:0, C20:4,n-6 and C22:6,n-3, with no significant difference in composition between the subfractions. 7. This paper provides the first description of a method for the isolation of three subfractions of HDL2b together with other subfractions in quantities that are sufficient for further analytical or metabolic studies. PMID- 1599434 TI - Interaction of 7-n-alkoxycoumarins with cytochrome P-450(2) and their partitioning into liposomal membranes. Assessment of methods for determination of membrane partition coefficients. AB - A study was made of the binding of 7-ethoxy-, 7-n-propoxy- and 7-n-pentoxy coumarin to cytochrome P-450(2) reconstituted into large unilamellar liposomes composed of a mixture of egg L-alpha-phosphatidylcholine, egg phosphatidylethanolamine and dipalmitoyl phosphatidic acid (2:1:0.06, by weight). The apparent spectral dissociation constants Ksapp. increased linearly with increasing proteoliposomal concentration. When both cytochrome P-450(2) and NADPH:cytochrome P-450 reductase were reconstituted into liposomes, the apparent Michaelis constants Kmapp. for O-dealkylation of 7-methoxy-, 7-ethoxy- and 7-n propoxy-coumarin showed a similar dependence on the proteoliposomal concentration. The results were in accordance with models for kinetic or equilibrium processes in biphasic systems containing membrane-bound catalytic or acceptor sites, in which a linear solute partition in the bilayer membrane is postulated. The methyl, ethyl and n-propyl ether were readily dealkylated. However, the O-dealkylation rate of 7-n-butoxycoumarin was low and became very small for longer alkyl ethers. Both the effective dissociation constants and effective Michaelis constants decreased with elongation of the alkyl side chain of the coumarins. From plots of the apparent dissociation constants and apparent Michaelis constants against the lipid volume fraction of the proteoliposomes, the membrane partition coefficients for several homologues were calculated. When protein-free liposomes were added to 7-n-alkoxycoumarin solutions, the fluorescence intensity of the coumarins decreased and eventually became negligible in the presence of an excess of liposomal material. On the assumption that the overall fluorescence can be ascribed exclusively to the fraction of 7-n alkoxycoumarin molecules present in the aqueous phase, partition coefficients for liposomal accumulation of the test compounds could be determined directly. For several coumarin ethers, comparable values were derived for the membrane partition coefficients from binding, kinetic and fluorescence intensity measurements. The change in free energy per methylene group of the 7-n alkoxycoumarins for partitioning between n-octanol and buffer was significantly different from the value for liposome partitioning. PMID- 1599435 TI - Oxidized glutathione causes sensitization of calcium release to inositol 1,4,5 trisphosphate in permeabilized hepatocytes. AB - The effects of GSSG on Ca2+ mobilization by Ins(1,4,5)P3 were studied in permeabilized rat hepatocytes. Incubation with GSSG (2 mM) increased the sensitivity to Ins(1,4,5)P3 for Ca2+ release, with no effect on the size of the Ca2+ pool that could be released with maximal concentrations of Ins(1,4,5)P3. GSSG decreased the EC50 for Ins(1,4,5)P3 from a control value of 578 +/- 23 nM to 137 +/- 21 nM. GSSG had no effect on the metabolism of Ins(1,4,5)P3 in permeabilized cells, and sensitization of Ca2+ release was still observed when the poorly metabolizable analogue inositol 1,4,5-trisphosphorothioate was used. GSSG did not affect the ATP-dependent Ca2+ pump or the extent of loading of intracellular Ca2+ pools. In addition, the enhancement of Ins(1,4,5)P3 sensitivity by GSSG occurred under conditions where the Ca2+ pumps were blocked with thapsigargin or by chelation of medium Ca2+ just before Ins(1,4,5)P3 addition. The effect of GSSG was time- and dose-dependent, maximal effects being observed after 5 min incubation with 2 mM-GSSG. Cystine mimicked the GSSG-induced increase in Ins(1,4,5)P3-sensitivity, and the effects could be reversed by dithiothreitol (DTT). DTT, GSH glutathione and cysteine had no effect when added alone. Other agents known to react with protein thiols, including N ethylmaleimide, p-chloromercuribenzoic acid and Ag+, did not affect the sensitivity to Ins(1,4,5)P3, but were inhibitors of ATP-dependent Ca2+ uptake. The data suggest that the sensitivity of the intracellular Ca2+ pools to release by Ins(1,4,5)P3 can be modulated by the formation of mixed disulphides with GSSG or other oxidized thiols. PMID- 1599437 TI - A thermostable NADH oxidase from anaerobic extreme thermophiles. AB - A high-abundance NADH-oxidizing enzyme (NADH: acceptor oxidoreductase, EC 1.6.99.3) has been identified and isolated from a range of anaerobic extreme thermophiles, including strains of Clostridium thermohydrosulfuricum and Thermoanaerobium brockii. By use of a pseudo-affinity salt-promoted adsorbent, a nearly pure sample was obtained in one step; remaining impurities were separated by ion-exchange. The fully active purified enzyme contains FAD (two molecules per subunit of 75-78 kDa) and iron-sulphur, and is hexameric in its most active form. The reaction with oxygen is a one- or two-electron transfer to produce superoxide radical and H2O2; other acceptors include tetrazolium salts, dichlorophenol indophenol, menadione and ferricyanide. The role of the enzyme is not clear; it was found not to be NAD:ferredoxin oxidoreductase, which is a major NADH utilizing enzyme in these organisms. PMID- 1599436 TI - Synergistic activation of phospholipase D by protein kinase C- and G-protein mediated pathways in streptolysin O-permeabilized HL60 cells. AB - Stimulation of phospholipase D (PLD) by cell surface receptors has been observed in many cell types. We have investigated the mechanism of activation of this enzyme in undifferentiated HL60 cells. GTP analogues and Ca2+ (buffered in the nanomolar to micromolar range) were introduced into HL60 cells in the presence of the permeabilizing agent, streptolysin O. We report that guanosine 5'-[gamma thio]triphosphate (GTP[S]) is a potent activator of phospholipase D when Ca2+ is available at micromolar levels. Phorbol 12-myristate 13-acetate or Ca2+ alone can also stimulate PLD, but to a limited extent. The activation of PLD by GTP[S] can be partially dissociated from GTP[S]-stimulated phosphoinositide-specific phospholipase C, suggesting that a G-protein may be directly involved in regulating PLD. However, maximal activation of PLD only occurs under conditions that are permissive to phospholipase C stimulation. We conclude that PLD activation is under dual control, i.e. protein kinase C- as well as G-protein mediated regulation. Synergistic activation occurs when both pathways are simultaneously stimulated. We conclude that full activation of PLD requires protein kinase C, increased Ca2+ and a GTP-binding protein. Evidence for cytosolic components that may also be involved in obtaining full activation of PLD is also presented. PMID- 1599439 TI - Amino acid deprivation leads to the emergence of System A activity and the synthesis of a specific membrane glycoprotein in the bovine renal epithelial cell line NBL-1. AB - 1. Amino acid deprivation of confluent monolayers of the bovine renal epithelial cell line NBL-1 causes a stimulation of Na(+)-dependent alanine transport. 2. This stimulation is mediated by a protein-synthesis-dependent induction of 2 (methylamino)isobutyric acid (methyl-AIB)-sensitive alanine transport activity (System A), which was not previously present in these cells. 3. Induction was prevented by the addition of methyl-AIB, alanine or glutamine. 4. Tunicamycin prevented the induction of alanine transport activity. 5. Induction of System A activity was accompanied by incorporation of [3H]mannose into a single membrane protein band of molecular mass 113-140 kDa. 6. These results are consistent with the possibility that induced System A activity in confluent NBL-1 cells is mediated by the synthesis of a 113-140 kDa membrane glycoprotein. PMID- 1599438 TI - Insulin receptor and epidermal growth factor receptor dephosphorylation by three major rat liver protein-tyrosine phosphatases expressed in a recombinant bacterial system. AB - Protein-tyrosine phosphatases (PTPases) play an essential role in the regulation of signal transduction mediated by reversible protein-tyrosine phosphorylation. In order to characterize individual rat hepatic PTPases that might have specificity for autophosphorylated receptor tyrosine kinases, we isolated cDNA segments encoding three PTPases (PTPase 1B, LAR and LRP) that are expressed in insulin-sensitive liver and skeletal muscle tissue, and evaluated their catalytic activity in vitro. The intrinsic PTPase activities of the full-length PTPase 1B protein and the cytoplasmic domains of LAR and LRP were studied by expression of recombinant cDNA constructs in the inducible bacterial vector pKK233-2 using extracts of a host strain of Escherichia coli that lacks endogenous PTPase activity. Each of the cloned cDNAs dephosphorylated a cognate phosphopeptide derived from the regulatory region of the insulin receptor. Despite having only 30-39% sequence identity in their catalytic domains, LAR and PTPase 1B had similar relative activities between the peptide substrate and intact insulin receptors, and also displayed similar initial rates of simultaneous dephosphorylation of insulin and epidermal growth factor (EGF) receptors. In contrast, LRP exhibited a higher rate of dephosphorylation of both intact receptors relative to the peptide substrate, and also dephosphorylated EGF receptors more rapidly than insulin receptors. These studies indicate that three PTPases with markedly divergent structures have the catalytic potential to dephosphorylate both insulin and EGF receptors in intact cells and that redundant PTPase activity may occur in vivo. For these PTPases to have specific physiological actions in intact cells, they must be influenced by steric effects of the additional protein segments of the native transmembrane enzymes, cellular compartmentalization and/or interactions with regulatory proteins. PMID- 1599441 TI - A comparison of mass spectrometric methods for the analysis of protein mixtures. PMID- 1599440 TI - N-terminal sequence of proteoglycan fragments isolated from medium of interleukin 1-treated articular-cartilage cultures. Putative site(s) of enzymic cleavage. AB - Bovine articular cartilage was cultured both in the presence and in the absence of human recombinant interleukin-1 alpha (IL-1) (100 units/ml). Addition of this cytokine stimulated matrix degradation approx. 3-fold. This increased degradation permitted characterization of the large chondroitin sulphate proteoglycan (aggrecan) fragments accumulating in the media. When compared with controls, the proteoglycans isolated from the medium of cultures treated with IL-1 exhibited a decrease in the Kav. (control 0.25; IL-1-treated 0.37), determined by Sepharose CL-2B chromatography. This decrease in proteoglycan size was accompanied by a decreased ability of these monomers to associate with hyaluronic acid. Thus only 20% of the proteoglycans isolated from the medium of IL-1-treated cultures, compared with 39% for control cultures, had the capacity to form high-M(r) aggregates with hyaluronic acid. SDS/PAGE analysis of the proteoglycans from the media of IL-1-treated cultures demonstrated several large proteoglycan protein core bands (M(r) 144,000-380,000). The protein-core bands with M(r) 144,000 266,000 exhibited a significantly decreased reactivity with monoclonal antibody 1 C-6 (specific for domains G1 and G2). The N-terminal amino acid sequence of four of these protein-core bands (M(r) 144,000, 173,000, 214,000 and 266,000) yielded sequences LGQRPPV-Y-PQLF(E), AGEGP(S)GILEL-GAP(S)-AP(D)M, GLG-VEL-LPGE and (A)RGSVIL-AKPDFEV-P-A. A comparison of these N-terminal amino acid sequences with the published proteoglycan sequence for bovine nasal cartilage [Oldberg, Antonsson & Heinegard (1987) Biochem. J. 243, 255-259], rat chondrosarcoma [Doege, Sasaki, Horigan, Hassell & Yamada (1987) J. Biol. Chem. 262, 17757-17769] and human articular cartilage [Doege, Sasaki, Kimura & Yamada (1991) J. Biol. Chem. 266, 894-902] permitted assignment of their relative positions on the core protein. Furthermore, on the basis of this similarity to published sequence, putative sites of enzymic cleavage were constructed. These theoretical cleavage sites revealed a glutamic acid residue in the P1 position and an uncharged polar or non-polar residue in the P1' position. PMID- 1599442 TI - Specificity constants in the context of protein engineering of two-substrate enzymes. PMID- 1599443 TI - An improved assay for pyruvate dehydrogenase in liver and heart. PMID- 1599444 TI - The product of the human MUC1 gene when secreted by mouse cells transfected with the full-length cDNA lacks the cytoplasmic tail. AB - The polymorphic epithelial mucin (PEM) is found as a cell associated transmembrane protein with an extracellular domain made up largely of tandem repeats and also as a soluble form in some body fluids and culture supernatants. To determine whether the soluble form can arise without the mechanism of alternative splicing mouse cells have been transfected with an expression construct containing the full-length cDNA, and the supernatants of the transfectants analyzed for the presence of the mucin. The presence of mucin in the supernatants could indeed be detected in a radioimmunoassay and by immunoprecipitation using monoclonal antibodies to the tandem repeat region of the core protein, indicating that release of the soluble form can occur without alternative splicing. The soluble form was not however precipitated with a polyclonal antiserum to the cytoplasmic tail, suggesting that it was released from the membrane by the action of a protease. PMID- 1599445 TI - 9-aminoacridine inhibits the B-Z transition of poly(dA-dT). AB - 9-Aminoacridine is the parent compound of a family of pharmacologically active model substances that bind to DNA through intercalation between base pairs. In the present study we show that 9-aminoacridine inhibits the B-to-Z isomerization of poly(dA-dT) in conditions that otherwise cause it to occur (5 M NaCl and 123 mM Ni(ClO4)2). Higher concentrations of Ni(ClO4)2 (155 mM) are able to induce the Z-form due to the disruption of the drug-polynucleotide interaction by the metal ion. Additionally, the dye reverses the Z-form in certain conditions. Thus, the data from this study indicate that 9-aminoacridine binds preferentially to the B form of poly(dA-dT). PMID- 1599446 TI - Expression of Drosophila's 27 kDa heat shock protein into rodent cells confers thermal resistance. AB - The role of hsp27, one of Drosophila melanogaster's small heat shock proteins, in the process of thermotolerance was investigated. The coding sequence of hsp27 was subcloned downstream of the human hsp27 promoter which has been shown to be constitutively expressed in Chinese hamster O23 cells. Cellular resistance to a thermal stress was measured two days after transfection by a survival assay following a 3.5 h heat treatment at 44 degrees C. Expression of Drosophila hsp27 was shown to confer thermal resistance to O23 cells in a manner which was dependent on the level of expression of this hsp. Immunoblot analysis confirmed that the thermal resistance was related to the expression of Drosophila hsp27 as none of the endogeneous hsps showed an increased level under these conditions. PMID- 1599447 TI - Effects of the histamine H3 receptor ligands thioperamide and (R)-alpha methylhistamine on histidine decarboxylase activity of mouse brain. AB - The effects of the histamine H3 receptor ligands thioperamide and (R)-alpha methylhistamine on the histidine decarboxylase (HDC) activity and histamine content of mouse brain were examined. Thioperamide, a histamine H3 antagonist, significantly increased the HDC activity in the brain of ddY, W/Wv and ICR mice 2 6 hr after its intraperitoneal (i.p.) injection. On the other hand, (R)-alpha methylhistamine, a histamine H3-receptor agonist, caused no significant change in the HDC activity. The whole brain histamine content of ddY mice decreased significantly to 60-70% of the control level 2-8 hr after injection of thioperamide (25 mg/kg, i.p.), but then increased to 90% of the control level 10 hr after the injection. These in vivo results showed that blockade of the presynaptic histamine H3-receptor, which causes release of presynaptic histamine, increased the HDC activity. PMID- 1599448 TI - Identification of cellular differentiation-dependent nuclear factors that bind to a human gene for thymidylate synthase. AB - Three nuclear factors were identified that interact with sequences in the 5' upstream region of the human thymidylate synthase gene. Two of these factors interact with a sequence around the initiation codon of the thymidylate synthase gene. The amounts of these two factors changed dramatically as human promyelocytic leukemia HL-60 cells differentiated into macrophage-like cells by the treatment with 1,25-dihydroxyvitamin D3. The change was closely correlated with the decrease in the amount of thymidylate synthase mRNA during the differentiation. These findings suggest that the specific nuclear factors are involved in the regulation of the expression of human thymidylate synthase gene during the differentiation of HL-60 cells. PMID- 1599449 TI - Two distinct pathways in the down-regulation of type-1 angiotension II receptor gene in rat glomerular mesangial cells. AB - The mRNA level of the type-1 angiotensin II receptor (AT1) was down-regulated by angiotensin II in cultured rat glomerular mesangial cells. The effect was maximum with 1 microM AII at 6 h, sensitive to cycloheximide, and specific to AT1 since this phenomenon was blocked by DuP753, an AT1 antagonist, but not by type-2 antagonist PD123319. Dibutyryl cAMP, forskolin, and cholera toxin also caused AT1 down-regulation. These effects were not altered by either the protein kinase A inhibitor H-8 or cycloheximide. Calcium ionophore A23187, pertussis toxin, protein kinase C inhibitor staurosporine, or prolonged incubation with phorbol ester were without effect. These results suggest that there are at least two pathways to down-regulate AT1 mRNA; one way is an angiotensin II-induced, protein kinase C-independent, and cycloheximide-sensitive pathway and the other is an angiotensin II-independent, cAMP-induced, and cycloheximide-insensitive pathway. PMID- 1599450 TI - Full sequence of neurocalcin, a novel calcium-binding protein abundant in central nervous system. AB - We determined the cDNA sequence for neurocalcin, a novel calcium-binding protein in bovine brain. This clone (pCalN) has 582 nucleotides in the open reading frame including the termination codon TGA, 11 nucleotides of the 5' leader and 1251 nucleotides of the 3' noncoding region. The deduced amino acid sequence revealed that neurocalcin is composed of 193 amino acids, has a molecular mass of 22,284 daltons, and contains three putative calcium-binding sites (EF-hand motifs). By Northern blot analysis, 3.8kbp mRNA was detected in brain. The deduced amino acid sequence had a strong homology to visinin (46.5%) and recoverin (51.6%) in retina, suggesting that neurocalcin may play a visinin- or recoverin-like role in brain. PMID- 1599451 TI - Lipopolysaccharide, latex beads and residual bodies are potent activators of Sertoli cell interleukin-1 alpha production. AB - Several recent studies indicate that interleukin-1 (IL-1) may be one of the major regulators of spermatogenesis. In the present work, the effects of various agents on rat Sertoli cell IL-1 production were investigated in vitro at different ages. In control cultures the IL-1 production by Sertoli cells from immature rats (20 days) was barely detectable; it markedly increased with the advancing age of the donors (35 and 45 days). Lipopolysaccharide and latex beads, two inducers of monocyte-macrophage IL-1 production, were able to stimulate the release of IL-1 by Sertoli cells at all ages studied; a decrease in the relative response to these inducers was noted as the age of the Sertoli cell donors increased. Under all the experimental conditions tested it appeared that the IL-1 produced was IL 1 alpha, not IL-1 beta. Whereas pachytene spermatocytes and early spermatids had no effect on IL-1 alpha production, residual bodies/cytoplasts from elongated spermatids dramatically stimulated Sertoli cell IL-1 production. In addition, FSH had no effect on IL-1 alpha levels. It is concluded that Sertoli cell IL-1 secretion can be stimulated in vitro by well known monocyte-macrophage activators. Furthermore, Sertoli cell IL-1 production is most probably crucially dependent on the phagocytosis of residual bodies in vivo. PMID- 1599452 TI - 31-P NMR characterization of the metabolic anomalies associated with the lack of glycogen phosphorylase activity in human forearm muscle. AB - Exercise-induced changes in phosphorus-containing metabolites and intracellular pH (pHi) have been studied in the finger flexor muscles of 3 patients with glycogen phosphorylase deficiency (McArdle's disease) in comparison to 14 healthy volunteers. At rest, no difference was observed for PCr/Pi ratio and pHi while patients exhibited a higher PCr/ATP ratio (5.91 +/- 0.98 vs 4.02 +/- 0.6). At end of-exercise, PCr/Pi was abnormally low (0.51 +/- 0.19 vs 1.64 +/- 0.37) whereas no acidosis was observed. The slow recovery of PCr/Pi ratio indicates an impairment of oxidative capacity accompanying the defect in the glycogenolytic pathway. The failure to observe a transient Pi disappearance at the onset of recovery (an index of glycogen phosphorylase activity) can be used in conjunction with the lack of exercise acidosis as a diagnostic index of McArdle's disease. PMID- 1599453 TI - Ion selectivity of Ba2+ inward current oscillations in ras-transformed fibroblasts that elicit cytoplasmic Ca2+ oscillations by bradykinin. AB - Ion selectivity of divalent cations on Ba2+ inward current oscillations was examined by voltage-clamp recording in v-Ki-ras-transformed NIH/3T3 (DT) fibroblasts where repetitive transient increases in cytoplasmic Ca2+ concentration were evoked by bradykinin. Application of bradykinin onto DT cells in 50 mM Ba2+ solution initiated Ba2+ inward current oscillations. The inward currents were inhibited in equimolar Sr2+ or Ca2+ solutions. Ba2+ current oscillations were dependent upon extracellular Ba2+ concentration. The results suggest that inward current oscillations are highly selective to Ba2+. PMID- 1599454 TI - Antibodies to the cytoplasmic domain of the MUC1 mucin show conservation throughout mammals. AB - An antiserum against the carboxy-terminal seventeen amino acids of the human MUC1 mucin has been raised and extensively characterized. This antiserum, CT1, immunoprecipitates two high molecular weight polymorphic bands (greater than 200 kDa) from a metabolically labelled breast cancer cell line corresponding to the two alleles which have previously been shown to contain different numbers of a twenty amino acid repeat. The CT1 antiserum reacted with tissues from many mammalian species and immunoprecipitated large polymorphic proteins, suggesting that the cytoplasmic portion of the molecule is well conserved. The cell and tissue distribution of Muc-1 mucin in the mouse has been studied by immunocytochemistry. This protein is abundant at the apical surfaces of epithelial tissues and is found expressed in the stomach, kidney, mammary gland, pancreas, salivary gland, lung, trachea, uterus, cervix and vagina. PMID- 1599455 TI - Substrate level modulation of the activity of phospholipase A2 in vitro by 12-O tetradecanoylphorbol-13-acetate. AB - The action of porcine pancreatic phospholipase A2 towards fluorescent phospholipid analogs is either enhanced or suppressed by 4 beta-12-O tetradecanoylphorbol-13- acetate (TPA), depending on the chemical structure of the substrate and the concentration of Ca2+. In the presence of nmolar Ca2+ concentrations increasing [TPA] enhanced by approx. 5-fold the rate of hydrolysis of the pyrene-labelled acidic alkyl-acyl phospholipid, 1-octacosanyl-2-[6- (pyrene-1-yl)] hexanoyl-sn-glycero-3-phosphatidylmethanol. Maximal effect was obtained at high TPA/substrate molar ratios approaching 1:2. In the presence of 4 mM CaCl2 maximal activation was reduced to approximately 1.5-fold. With the corresponding phosphatidylcholine derivative as a substrate increasing [TPA] reduced fatty acid release maximally by 90% both at low [Ca2+] as well as in the presence of 4 mM CaCl2. Essentially identical results were obtained using 4 alpha TPA, a stereoisomer which does not activate protein kinase C. PMID- 1599456 TI - 22-oxacalcitriol suppresses 25-hydroxycholecalciferol-1 alpha-hydroxylase in rat kidney. AB - 22-oxacalcitriol can decrease the serum level of 1,25-dihydroxycholecalciferol by increasing its metabolic clearance rate and decreasing its production rate. To determine whether 22-oxacalcitriol suppressed the renal 25-hydroxycholecalciferol 1 alpha- hydroxylase we treated rats with 200 ng of 22-oxacalcitriol daily for 1 week. Enzyme activity was measured in vitro by measurement of production of 1,25 dihydroxycholecalciferol by renal slices incubated with 25 hydroxycholecalciferol. 22-oxacalcitriol significantly decreased the 25 hydroxycholecalciferol-1 alpha-hydroxylase activity from 797 +/- 208 pg of 1,25 dihydroxycholecalciferol/g of kidney/h in the control group to 257 +/- 150 pg of 1,25-dihydroxycholecalciferol/g of kidney/h (p less than 0.05). This is the first demonstration of suppression of the renal 25-hydroxycholecalciferol-1 alpha hydroxylase by the vitamin D3 analog, 22-oxacalcitriol. PMID- 1599458 TI - Regulation of rat hepatic peroxisomal enoyl-CoA hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme by thyroid hormone. AB - Rat hepatic t protein that is negatively regulated by thyroid hormone in nuclear globulin extract was characterized by the antibodies. The following evidence indicated that t protein is a peroxisomal enoyl-CoA hydratase-3-hydroxyacyl-CoA dehydrogenase bifunctional enzyme (bifunctional enzyme). 1. Both proteins had an identical molecular size, and were immunologically indistinguishable from each other. 2. The t protein was abundant in mitochondrial fraction which contained abundant peroxisomes. 3. The amount of the t protein was increased by a peroxisomal proliferator. 4. The activity of the peroxisomal bifunctional enzyme corresponded to the t protein in CM-Sephadex column chromatography. The amount of peroxisomal bifunctional enzyme was increased by thyroidectomy and decreased by 3,5,3'- triiodo-L-thyronine treatment in the whole homogenate of rat liver. These results indicate that the levels of peroxisomal bifunctional enzyme were regulated by thyroid hormone in vivo. PMID- 1599459 TI - Expression and purification of biologically active human OSF-1 in Escherichia coli. AB - OSF-1 (also known as pleiotrophin, HB-GAM, HBGF-8 or HBNF) is a heparin-binding, neurotrophic protein. Its tissue-specific expression in rats is developmentally regulated and the protein is highly conserved between species. The protein is believed to be involved in neuronal development. Previous experiments in our laboratory showed that OSF-1 is primarily expressed in brain and bone. The biological function of OSF-1 in bone is unknown. In order to overcome the limited availability of the native protein, we now report on the high-level expression of human OSF-1 in Escherichia coli. The protein is present in the form of inclusion bodies, which were isolated and solubilized. The partially purified protein was refolded and further purified employing heparin sepharose chromatography. N terminal sequence determination revealed the same amino acid sequence as the natural mature protein. The isolated backfolded recombinant human OSF-1 did promote neurites outgrowth in primary cultures of cortical neurons. PMID- 1599460 TI - Isolation of a cDNA clone encoding the RNase-superfamily-related gene highly expressed in chicken bone marrow cells. AB - The RNase gene superfamily combines functionally divergent proteins which share statistically significant sequence similarity. Known members assigned to this family include secretory and nonsecretory RNases; angiogenin; eosinophil cationic protein; eosinophil-derived neurotoxin; sialic-acid binding lectin and anti-tumor protein P-30. We report the cDNA cloning of the chicken RNase Super Family Related (RSFR) gene that is specifically overexpressed in normal bone marrow cells and bone marrow-derived AMV transformed monoblasts. It codes for a 139 amino acid protein with a putative signal peptide and remarkable conservation of active-site residues, other residues known to be important for substrate binding and catalytic activity and half-cystine residues common for all RNase family members. Phylogenetic tree analysis shows that RSFR defines a new group of genes within the family. We also conclude that an amino acid sequence block CKXXNTF(X) 11C is a "shortest RNase superfamily signature" which is both necessary and sufficient to identify all previously recognized family members as well as chicken RSFR. PMID- 1599457 TI - Characterization of an angiotensin type-1 receptor partial cDNA from rat kidney: evidence for a novel AT1B receptor subtype. AB - We sought to determine if multiple forms of mRNA for the angiotensin type-1 (AT1) receptor could be detected in rat kidney using the polymerase chain reaction (PCR) procedure. Amplification of rat kidney cDNA with oligonucleotide primers derived from the second and sixth transmembrane domains of the rat AT1 receptor yielded a single cDNA fragment 528bp in size. Sequence analysis indicated, however, that the cDNA fragment was a mixture of two highly similar gene products: the first cDNA was identical to the previously cloned AT1 receptor (termed here AT1A) whereas the second cDNA (termed here AT1B) was 92% identical at the nucleotide level and 96% identical at the amino acid level. Nucleotide substitutions were dispersed throughout the cDNA and 80% (33 of 41) were conservative. Significant levels of AT1A and AT1B mRNA were detected by PCR amplification of kidney poly(A)+ RNA and restriction enzyme analysis. These results indicate that at least two distinct AT1 receptor genes are expressed in rat kidney. PMID- 1599461 TI - Cloning, characterization, and expression of two angiotensin receptor (AT-1) isoforms from the mouse genome. AB - We report the existence of two structurally distinct forms of the angiotensin receptor AT-1 in the mouse. A Balb/c mouse genomic library was screened by homology screening with a polymerase chain reaction (PCR) amplified probe. Restriction mapping and sequencing of the isolated genes revealed the presence of two receptor isoforms, here named the mouse AT-1a and AT-1b receptors, containing 22 different amino acids. Receptor binding studies performed on COS-7 cells transfected with the two receptors revealed that they had similar binding profiles for angiotensin II, angiotensin III and AT-1 or AT-2 specific antagonists. Because many of the structural differences were in the carboxy terminal putative intracellular domain, we speculate that these isoforms may differ in their regulation, signal transduction, or desensitization mechanisms. PMID- 1599462 TI - Differential regulation of rat liver selenoprotein mRNAs in selenium deficiency. AB - Selenium deficiency causes a fall in the concentrations of selenoproteins but selenoprotein P and type I iodothyronine 5'-deiodinase (5'-deiodinase) are more resistant to this effect than is glutathione peroxidase. To investigate the differential regulation of these selenoproteins, a selenium-deficient diet was fed to weanling rats for 14.5 weeks and their hepatic mRNAs were measured by Northern analysis. Levels of all 3 mRNAs fell progressively with time. Selenoprotein P and 5'-deiodinase mRNAs remained higher at all time points relative to control than glutathione peroxidase mRNA. mRNA decreases were mirrored by decreases in glutathione peroxidase activity and selenoprotein P concentration. However, the decreases in the protein levels were greater than the decreases in their mRNAs, suggesting that synthesis of both proteins was limited to a similar extent at the translational level by the availability of selenium. In addition to this apparently unregulated translational effect, these results point to a pretranslational regulation, affecting mRNA levels, which could account for the differential effect of selenium deficiency on glutathione peroxidase and the other selenoproteins. This regulation might serve to direct selenium to selenoprotein P and 5'-deiodinase when limited amounts of the element are available. PMID- 1599464 TI - Mouse and human hemopoietic cell lines of erythroid lineage express lamins A,B and C. AB - Using monoclonal antibodies, we have studied the expression of lamins A,B,C and vimentin in mouse and human erythroleukemia cells. We have found that in contrast with previous reports these cells have all three lamins. Mouse cells lack vimentin, whereas human cells express it. Lamins B and C are the most abundant lamins, whereas considerably less lamin A is detectable. Our results argue that some mouse and human hemopoietic cells can express all three lamins and that production of vimentin does not necessarily precede that of lamins A/C, as other reports have suggested in the past. The data also show that the absence of a salt resistant inner nuclear matrix is not always related with the lack of lamins A/C and vimentin, as recently proposed. PMID- 1599463 TI - The identification of a tandem H-DNA structure in the c-myc nuclease sensitive promoter element. AB - Previous studies have shown that the c-myc nuclease sensitive element (NSE) is capable of forming H-DNA in vitro. The NSE sequence exhibits strong purine/pyrimidine strand asymmetry. To study the NSE further, we have isolated the element from other c-myc sequences and have shown that the NSE alone is sufficient for the formation of H-DNA in supercoiled plasmids. We also show that the NSE forms a complex structure containing both H-y3 and H-y5 H-DNA. We term this structure tandem H-DNA. PMID- 1599465 TI - Molecular cloning of a novel adenosine receptor gene from rat brain. AB - We have isolated an adenosine receptor gene (RA2) from a rat brain cDNA library. This novel rat adenosine receptor has 410 amino acids, as deduced from its base sequence, and shows 82% amino acid identity with the dog A2 receptor. Amino acid sequence analysis indicates that RA2 protein contains seven transmembrane domains and belongs to the G protein-coupled receptor family. The variations in amino acid sequences between RA2 protein and the dog A2 receptor are largely confined to the extracellular second loop and the carboxyl terminus. PMID- 1599467 TI - Inactivation of 5-enolpyruvylshikimate 3-phosphate synthase by its substrate analogue pyruvate in the presence of sodium cyanoborohydride. AB - Incubation of Escherichia coli 5-enolpyruvylshikimate 3-phosphate synthase with its substrate analogue pyruvate in the presence of sodium cyanoborohydride resulted in a significant decrease in its enzyme activity. The inactivation followed pseudo-first order and saturation kinetics with a Kinact of 16.12 mM and a maximum rate of constant of 0.046 min-1. The inactivation was specifically prevented by preincubation of the enzyme with a combination of the substrate shikimate 3-phosphate plus competitive inhibitor glyphosate. Upon 90% inactivation, approximately 1 mole of [14C]-label from [14C]-pyruvate was incorporated per mole of enzyme. Tryptic mapping of the modified enzyme as well as analysis of an isolated radioactive peptide indicated that Lys22 was the modified site. The results suggested that pyruvate inactivated the enzyme by forming a Schiff-base with Lys22 at the enzyme's active site. PMID- 1599466 TI - An amino acid change in the DNA-binding region of Sry, found in Mus musculus domesticus and other species, does not explain C57BL/6J-YDOM sex-reversal. AB - Sry is the testes determining factor gene located on the Y chromosome. We have performed dideoxy sequencing or restriction enzyme digestion of Sry sequences amplified by PCR from a variety of inbred strains and species of mice. A nonconservative replacement of Thr for Isoleu at position 61 was found in Sry from the Y chromosome of Mus musculus domesticus, Mus spretus, and Mus caroli. We demonstrate that this variation is not sufficient to explain the gradiation in the sex-reversal seen when different domesticus strains are bred to C57BL/6J females. PMID- 1599468 TI - Epoxidation of 2,3-oxidosqualene to 2,3;22,23-squalene dioxide by squalene epoxidase. AB - Partially purified squalene epoxidase (SE) from pig liver converts 2,3 oxidosqualene (SO) to 2,3;22,23-squalene dioxide (SDO) with approximately one half the efficiency of the epoxidation of squalene at pH 7.4. The SO to SDO conversion is independent of pH and shows an absolute requirement for exogenous FAD. Two noncompetitive SE inhibitors show selectivity in blocking squalene (Sq) to SO versus SO to SDO epoxidations. Finally, SDO inhibits the activity of crude pig liver oxidosqualene cyclase (OSC) with an IC50 of 16 microM. Thus, SE inhibitors not only reduce the production of SO from Sq, but also strongly suppress "leakage" of SO to the potentially harmful SDO in vitro. PMID- 1599469 TI - CCP II: a novel calcitonin carboxy terminal peptide is expressed in normal thyroid tissue. AB - We have recently identified in medullary thyroid carcinoma the existence of a second calcitonin messenger, generated by a splicing between the 3' coding region of exon 4 and exon 5 of Calc I gene. It differs from the first one in its 3' coding sequence and codes for a calcitonin precursor which generates the same N terminal peptide, calcitonin and a specific 21 amino acid carboxy terminal peptide differing from Katacalcin by its 8 last amino acids. We searched for the expression of this new messenger in normal human thyroid tissue by Northern and by polymerase chain reaction techniques. This second calcitonin messenger was expressed in 4/4 normal thyroids and 4/5 medullary thyroid carcinoma tissue samples. The expression of this second messenger is apparently a common occurrence in C cells whether normal or tumoral. PMID- 1599470 TI - Structural and functional similarity between fish antifreeze proteins and calcium dependent lectins. AB - A cDNA for a type II antifreeze protein was isolated from liver of smelt (Osmerus mordax). The predicted protein sequence is homologous to that from sea raven (Hemitripterus americanus) and both show homology to a family of calcium dependent lectins. Smelt and sea raven belong to taxonomic orders believed to have diverged prior to Cenozoic glaciation. Thus, type II antifreeze proteins appear to have evolved independently in these fish species from pre-existing calcium-dependent lectins. Sequence alignment of the antifreezes and the lectins suggest that these proteins adopt a similar fold, that the sea raven antifreeze has lost its Ca2+ binding sites, and the smelt antifreeze has retained one site. Experiments show that smelt antifreeze protein activity is responsive to Ca2+ but that of sea raven antifreeze protein is not. These results suggest that the type II fish antifreeze proteins and calcium-dependent lectins share a common ancestry, related folding structures, and functional similarity. PMID- 1599471 TI - Ontogeny of cytosolic phospholipase A2 activity in rat brain. AB - We investigated developmental changes in the activity of cytosolic phospholipase A2 (cPLA2) in the rat brain. When the cytosolic fractions from rat brain of various ages were examined by gel filtration chromatography, cPLA2 activity was detected at about 100 kDa in all developmental stages. However, the magnitude of cPLA2 activity differed significantly. The cPLA2 activity was highest in the brain of day-12 embryo, gradually decreased toward birth, and retained a constant level into adulthood. This result suggests that cPLA2 plays an important role in the early development of the nervous system. PMID- 1599472 TI - The primary structure of rat ribosomal protein L11. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L11 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L11 has 178 amino acids and a molecular weight of 20,239. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 6-8 copies of the L11 gene. The mRNA for the protein is about 800 nucleotides in length. Rat L11 is homologous to ribosomal proteins from other eukaryotes and is related to the L5 family of proteins from eubacterial and archaebacterial ribosomes. PMID- 1599473 TI - Sodium-dependent potassium (86Rb+) efflux moderates volume regulation by cells in rat renal inner medullary slices exposed to strongly hyperosmotic media. AB - The possibility has been examined that Na(+)-dependent K(+)-conductive pathways, known to exist in certain excitable cell membranes and inhibitable by the drug R56865, may also be present in cells of rat renal inner medulla, and that their activation may explain aspects of volume regulation by these cells in tissue slices exposed to strongly hyperosmotic media, as reflected by the rate of efflux of preloaded 86Rb+ (a marker for K+) and steady-state cell volumes and K+ contents. Cells incubated in media of 2000 mosmol/kg (400 mM Na+, 1172 mM urea) shrink and lose K+ by comparison with those in 720 mosmol/kg (203 mM Na+, 266 mM urea). If 2-aminisobutyric acid (10 mM) is added there is partial restoration of cell volume due to inwardly directed Na(+)-amino acid cotransport, but 86Rb+ efflux is accelerated and cells fail to regain net K+. R56865 (5 microM) completely blocks the increase in efflux and causes marked increases in cell volume and K+ contents, but only in strongly hyperosmotic media and in the presence of both Na+ and amino acid. In mildly hyperosmotic media, or media of 2000 mosmol/kg from which Na+ or amino acid is omitted, R56865 is without effect on these variables. PMID- 1599474 TI - Effects of changes in membrane potential on the cyclosporin-induced inhibition of T-cell proliferation. AB - Cyclosporin A (CsA) exerts its major immunosuppressive effect by inhibition of T lymphocyte proliferation. The precise mechanism and target of its action has not yet been completely identified. CsA is also known to induce a rapid membrane depolarization in T lymphocytes. We have tested the role of CsA-dependent depolarization in the inhibition of T-cell proliferation by the drug. In these studies, induced membrane depolarization (in the presence of gramicidin or by replacing the Na+ content of the medium with K+) or hyperpolarization (in the presence of valinomycin) had no influence on the induction of T-cell competence by phorbol dibutyrate/ionomycin or by submitogenic concentrations of PHA, a target for CsA immunosuppression. However, regardless of the state of membrane potential during the induction of T-cell competence, the inhibition by CsA was the same as seen in normally polarized cells. We conclude that the depolarization induced by CsA is not a critical element in its inhibitory effect on T-cell proliferation. PMID- 1599475 TI - Substrate based inhibitors of smooth muscle myosin light chain kinase. AB - Activation of myosin light chain kinase is a prerequisite for smooth muscle activation. In this study, short peptide analogs of the phosphorylation site of the myosin light chain were studied for their effects on several contractile protein systems. The peptides inhibited phosphorylation of isolated ventricular and smooth muscle myosin light chains by smooth muscle myosin light chain kinase, but they were only weak inhibitors of phosphorylation of intact myosin and actomyosin. The peptides were also unable to block force development or myosin light chain phosphorylation in glycerol permeabilized fibers of swine carotid media. Apparently, the association of the myosin light chain with myosin changes its conformation such that substrate analogs which are potent inhibitors of the phosphorylation of isolated myosin light chains by myosin light chain kinase are ineffective at blocking phosphorylation of the intact molecule. PMID- 1599476 TI - Extraction and characterisation of the intact form of bovine vitreous type IX collagen. AB - We provide the first biochemical characterisation of intact type IX collagen extracted from bovine vitreous. It possesses a shortened alpha 1(IX) chain (M(r) 64K) compared to its cartilage counterpart (M(r) 84K). All the vitreous type IX collagen is in a proteoglycan form, its glycosaminoglycan constituent being a chondroitin/dermatan sulphate component of M(r) 15-60K attached to the alpha 2(IX) chain. This contrasts with previous findings in chick vitreous where a very long glycosaminoglycan chain of M(r) approximately 350K was demonstrated. PMID- 1599477 TI - Kex2-like proteolytic activity in adrenal medullary chromaffin granules. AB - This study demonstrates the presence of boc-Gln-Arg-Arg-MCA cleaving activity in bovine chromaffin granule membranes that resembles yeast Kex2 proteolytic activity. The chromaffin granule boc-Gln-Arg-Arg-MCA cleaving activity, like Kex2 proteolytic activity, shows calcium dependence, optimum activity at pH 7.5-8.2, inhibition by serine protease inhibitors, and preference for cleavage at the COOH terminal side of Arg-Arg and Lys-Arg, over Lys-Lys, paired basic residues. Potent inhibition by the active-site directed inhibitor [D-Tyr]-Glu-Phe-Lys-Arg-CK (20 microM) provided further evidence for dibasic residue cleavage site specificity. These results are the first report of endogenous mammalian Kex2-like proteolytic activity that may be related to PC1/PC3 and PC2 enzymes, the newly discovered mammalian homologues of Kex2 protease. It will be important to determine the role of this Kex2-like proteolytic activity in processing the precursors of adrenal medullary neuropeptides. PMID- 1599478 TI - Expression of E. coli tag gene encoding 3-methyladenine glycosylase I in NIH-3T3 murine fibroblasts. AB - NIH-3T3 fibroblasts were co-transfected with pSV2neo and pSG5tag by the calcium phosphate precipitation method. The stable integration of the tag gene sequence and its transcription was verified by Southern and Northern blot analysis. 3 Methyladenine glycosylase activity in pSG5tag transfected 3T3 cells was approximately 400 times higher than in cells transfected with the control plasmid pSG5 or in the parental cells and was inhibited by 3-methyladenine. Bacterial tag gene can thus be expressed in mammalian cells and the encoded enzyme is functionally active. These transfected cells could serve as an important tool to investigate the importance of the repair of N3-adenine as a mechanism of protection against the mutagenicity and cytotoxicity of alkylating agents. PMID- 1599479 TI - Acetylation and methylation of histones H3 and H4 in chicken immature erythrocytes are not directly coupled. AB - The relationship between histone methylation and dynamic histone acetylation was investigated. Previously, we demonstrated in chicken erythrocytes that dynamically acetylated histones H3 and H4 of transcriptionally active gene chromatin were selectively methylated. However, methylation of these histones was not dependent upon their acetylated states. Here, we tested the hypothesis that methylation tags these histones for participation in dynamic acetylation. Using an inhibitor of protein methylation, adenosine dialdehyde, we show that the processes of histone methylation and dynamic acetylation are not directly coupled. Our results suggest that the selective methylation of dynamically acetylated chromatin reflects features of the organization of transcriptionally active gene chromatin. PMID- 1599480 TI - Identification of an interleukin-6 responsive element and characterization of the proximal promoter region of the rat hemopexin gene. AB - The rat hemopexin (Hx) gene was isolated and studies of its transcriptional regulation initiated. For analysis by a transient expression assay, the sequence between -2400 and +21 and sequential 5' truncates were linked to the chloramphenicol acetyltransferase (CAT) gene. HepG2 cells transfected with these CAT constructs were treated with conditioned medium of lipopolysaccharide stimulated human monocytes, interleukin-1 (IL-1) or interleukin-6 (IL-6). The activities of putative regulatory regions joined to the SV40 promoter indicated that the flanking region of the rat Hx gene from -209 to -104 contains three functional regions designated proximal regulatory regions; PRR-I (-209 to -173), II (-178 to -158) and -III (-154 to -104). We found that PRR-II contains a different class of IL-6 responsive element (RE) from that reported for the human Hx gene, and that PRR-I and PRR-III participate in the basal expression of rat Hx in HepG2 cells. PMID- 1599481 TI - Endotoxin and TNF alpha directly stimulate nitric oxide formation in cultured rat hepatocytes from chronically endotoxemic rats. AB - We examined the effects of endotoxin on nitric oxide formation in isolated rat hepatocytes in primary culture. Endotoxin was administered either in vivo, by continuous infusion for 30 or 3 h, or in vitro, on cultured cells. The spontaneous production of nitrites in hepatocytes from in vivo ET-infused rats was lower than equivalent saline controls in the absence of added stimuli. However in vitro addition of endotoxin in culture to hepatocytes from 30 h ET infused rats greatly enhanced production relative to saline controls. This effect was mimicked by TNF alpha, and activators of protein kinase C (PMA and Ca2+ ionophore A23187). The effects of ET were blocked by NMMA, dexamethasone and protein synthesis inhibitors Actinomycin D and cycloheximide. No in vitro effect of ET was observed in the 3 h infusion model. The results show that chronic exposure to sub-lethal levels of ET primes liver parenchymal cells for the production of nitric oxide, when exposed in vitro to ET or TNF alpha. PMID- 1599482 TI - Genomic structure of the ME491/CD63 antigen gene and functional analysis of the 5'-flanking regulatory sequences. AB - Genomic structure of the ME491/CD63 antigen gene and promoter activity of the 5' flanking regulatory sequences were studied. The antigen gene consists of eight exons that span 4 kilobase-pairs. Primer extension analysis with RNA from cultured human cells identified three major transcription initiation sites. The 5'-flanking region of exon 1 has features characteristic to promoters of many house-keeping genes and growth-regulating genes. The region is highly GC rich and contains potential binding sites for transcription factors such as Sp1 and ETF, but not a TATA box. The 5'-flanking sequence exerted strong promoter activity when linked to a reporter gene. Deletion mutant analysis of the 5'-flanking sequence has strongly suggested that a potential binding site for AP-1 plays an important role in positively regulating the gene expression. PMID- 1599483 TI - Trichloroethylene oxidation by toluene dioxygenase. AB - Trichloroethylene was oxidized by purified toluene dioxygenase obtained from recombinant E. coli strains. The major oxidation products were formic acid and glyoxylic acid. Other potential products, dichloroacetic acid, chloral, phosgene, carbon monoxide, and carbon dioxide, were not detected. [14C]trichloroethylene became covalently attached to protein components and NADPH suggesting non specific alkylation by reactive products. Oxidation of deuterated trichloroethylene yielded 50.2% deuterated formate. Oxidation of trichloroethylene in D2O yielded 43.7% deuterated formate. These data indicate that both carbon atoms are giving rise to formic acid. The results are consistent with a mechanism of TCE oxygenation not involving epoxide, dioxetane, or dihydroxy intermediates and indicate significant differences from those previously proposed for cytochrome P-450 (Miller, R.E. & Guengerich, F.P. (1982) Biochemistry 21, 1090-1097) or methane monooxygenase (Fox, B.G., Borneman, B.G., Wackett, L.P., & Lipscomb, J.D. (1990) Biochemistry 29, 6419-6227). PMID- 1599484 TI - Formation of nitric oxide by cytochrome P450-catalyzed oxidation of aromatic amidoximes. AB - Rat liver microsomes catalyze the oxidation of para-hexyloxy-benzamidoxime 1 to the corresponding arylamide 2 and NO2-, by NADPH and O2. Involvement of cytochromes P450 as catalysts of this reaction was shown by the strong inhibitory effects of CO and miconazole and the spectacular increase of the activity upon treatment of rats with dexamethasone, a specific inducer of cytochromes P450 of the 3A subfamily. Formation of NO during oxidation of 1 was shown by detection of the formation of cytochrome P450- and cytochrome P420-Fe(II)-NO complexes by visible and EPR spectroscopy. The formation of these complexes should be responsible, at least in part, for the fast decrease of the rate of microsomal oxidation of 1 with time. These results suggest that exogenous compounds containing amidine or amidoxime functions could act as precursors of NO in vivo after in situ oxidation by cytochromes P450. PMID- 1599485 TI - Phospholipase A2-modified LDL is taken up at enhanced rate by macrophages. AB - Modification of the low density lipoprotein (LDL) core or surface lipids were shown to affect the cellular uptake of the lipoproteins and hence the formation of foam cell macrophages. In the present study phospholipase A2 treatment of LDL was shown to produce negatively charged lipoprotein with increased content of lysolechitine. This modified lipoprotein was taken up and degraded by J-774 A.1 macrophage-like cell line at enhanced rate (up to 97% when 10 units/ml of PLase A2 was used) in comparison to control LDL. This effect of PLase A2 was enzyme dose dependent. Competition experiments revealed that the uptake of PLase A2-LDL by the macrophages was specific and was mediated via the LDL receptor. Since PLase A2 was found to exist in various tissues, thus the production of PLase A2 LDL under certain pathological conditions can potentially contribute to foam cell formation and accelerated atherosclerosis. PMID- 1599486 TI - A new mathematical model to study bone turnover in growing rats. AB - A new mathematical model for the study of bone turnover in growing rats was developed. The model predicts a linear relationship between bone mineral content (BMC) and biochemical markers (BMK) of bone turnover assuming that rats are growing, bone turnover is profoundly affected by skeletal maturation, and resorption and formation are physiologically balanced. The model validation was performed by measuring galactosyl-hydroxylysine (GHYL) and hydroxyproline (HYP) in urines. This mathematical evidence supports our proposed use of the specific bone resorption marker GHYL to predict bone mineral content. Further studies on bone turnover will be possible by the application of the same approach. PMID- 1599487 TI - Cooperative function of rho GDS and rho GDI to regulate rho p21 activation in smooth muscle. AB - The GDP/GTP exchange reaction of rho p21, a member of ras p21-related small GTP binding protein superfamily, is regulated by two stimulatory GDP/GTP exchange proteins (GEPs), named smg GDS and rho GDS, and by one inhibitory GEP, named rho GDI. In bovine aortic smooth muscle, rho GDS and rho GDI were major GEPs for rho p21, and the rho GDI activity on the GDP/GTP exchange reaction of rho p21 was stronger than the rho GDS activity in their simultaneous presence. Moreover, in the crude cytosol, the GDP-bound form of rho p21 was complexed with rho GDI but not with rho GDS. These results, together with our recent finding that rho p21 is involved in the vasoconstrictor-induced Ca2+ sensitization of smooth muscle contraction, suggest that there is some mechanism to release the inhibitory action of rho GDI and to make rho p21 sensitive to the stimulatory action of rho GDS, eventually leading to the rho p21 activation, in the signaling pathways of the vasoconstrictor receptors in smooth muscle. PMID- 1599488 TI - Conformational changes of actin induced by calponin. AB - Calponin, an actin-linked regulatory protein in smooth muscle, caused a remarkable change in the fluorescence intensity of pyrene-labeled actin in the filamentous form. Calponin, an equimolar ratio to actin, decreased the fluorescence intensity of pyrene-labeled F-actin by some 60% to the level near monomeric actin. This change was partially reversed by Ca2+, when calmodulin was present. Thus it appears that calponin causes conformational changes in actin molecules in an actin filament so as to inhibit their interactions with myosin. PMID- 1599489 TI - Subcellular localisation of guinea pig hepatic molybdenum hydroxylases. AB - Molybdenum hydroxylase activity in guinea pig liver has been compared with that of marker enzymes in mitochondria (succinate dehydrogenase), microsomes (glucose 6-phosphatase) and cytosol (lactate dehydrogenase). Aldehyde oxidase activity was highest in the cytosol, with about 10-fold activity of xanthine oxidase. Significant molybdenum hydroxylase activity was found in mitochondria with minimal levels in microsomes. Mitochondrial and cytosolic aldehyde oxidase varied in substrate specificity and electrophoretic mobility with two major bands in each fraction, one of which was common to cytosol and mitochondria. PMID- 1599491 TI - Inhibition of HIV-1 integration protein by aurintricarboxylic acid monomers, monomer analogs, and polymer fractions. AB - Several aurintricarboxylic acid (ATA) monomers, monomer analogs, and polymer fractions have been tested as inhibitors of HIV-1 integration protein (IN). Both of the ATA monomers and all of the ATA polymer fractions inhibited a selective DNA cleavage reaction catalyzed by IN. The ATA monomer analogs were inactive or had low activity. The activities of the substances as inhibitors of HIV IN correlated in a positive way with their activities as inhibitors of the cytopathic effect of HIV-1 in CEM and HIV-2 in MT4 cells. These results suggest that inhibition of HIV IN may contribute to the antiviral activity of the ATA monomers and monomer analogs in cell culture. PMID- 1599490 TI - The enantioselective participation of (S)- and (R)-diaminovaleric acids in the formation of delta-aminolevulinic acid in cyanobacteria. AB - Although it is recognized that 4,5-diaminovaleric acid, formed from glutamate 1 semialdehyde, functions as the intermediate in the last step of delta aminolevulinic acid formation from glutamate, the enantioselectivity of the participating glutamate 1-semialdehyde aminotransferase for 4,5-diaminovaleric acid has remained unknown. In the present work the involvement of (S)- and (R) 4,5-diaminovaleric acids, newly available by organic synthesis, was investigated, using glutamate 1-semialdehyde aminotransferase from Synechococcus. The preferred enantiomer was (S)-4,5-diaminovalerate. In experiments on the transformation of (S)-4,5-diaminovalerate to delta-aminolevulinate it was found that glutamate 1 semialdehyde aminotransferase was unusual among aminotransferases in that the common amino acceptors pyruvate, oxaloacetate, alpha-ketoglutarate were inactive, while 4,5-dioxovaleric acid could be utilized as a sluggish amino acceptor in place of glutamate 1-semialdehyde. In conclusion, glutamate 1-semialdehyde aminotransferase is highly but not absolutely enantioselective for (S)-4,5 diaminovaleric acid, and 4,5-dioxovaleric acid can function as amino acceptor not because of a physiological role in the C5 pathway of delta-aminolevulinic acid formation, but because of its structural resemblance to glutamate 1-semialdehyde. PMID- 1599493 TI - Lyn, a src-like tyrosine-specific protein kinase, is expressed in HL60 cells induced to monocyte-like or granulocyte-like cells. AB - During the in vitro differentiation of HL60 cells tyrosine-specific kinases are activated. The expression of lyn, a src-related tyrosine kinase, was studied by analysis of the steady-state levels of its transcript during the cell differentiation process induced by retinoic acid, phorbol 12-myristate 13-acetate and 1,25-dihydroxyvitamin D3. In contrast to an earlier report we observe only a small induction of the lyn-RNA levels compared to uninduced control cells. In unstimulated HL60 cells, the level for the lyn-transcript was comparatively high. A second, minor human lyn-transcript with an estimated size of 3.7 kb which has not been previously described, was identified. PMID- 1599492 TI - In vitro assays of three carotenogenic membrane-bound enzymes from Escherichia coli transformed with different crt genes. AB - In vitro assays have been developed for three membrane-bound carotenogenic enzymes, phytoene desaturase, lycopene cyclase and beta-carotene hydroxylase, expressed in Escherichia coli. Transformants of E. coli containing different deletion constructs of the Erwinia herbicola carotenogenic gene cluster were employed, allowing the estimation of enzyme activities without interference from subsequent reactions. New HPLC systems were developed to separate substrates and reaction products enabling the determination of radioactivity on-line. The newly developed assays facilitate the purification of these enzymes which have never been isolated before. PMID- 1599495 TI - Inhibition and metabolite complexation of rat hepatic microsomal cytochrome P450 by tricyclic antidepressants. AB - Administration of imipramine (IMIP) and other tricyclic antidepressants to humans and experimental animals has been associated with inhibition of hepatic cytochrome P450 (P450)-mediated drug oxidation. This study investigated the capacity of several structurally related tricyclic antidepressants to inhibit microsomal P450 activity in vitro. It was found that IMIP, desipramine (DES), amitriptyline (AMIT) and nortriptyline (NOR) were poor inhibitors of P450 activity unless they were preincubated with microsomes and NADPH prior to transfer to flasks containing substrate. Thus, subsequent experiments characterized the time-dependent intensification of inhibition produced by the drugs. Preincubation of the N-methylaminoalkyl agents DES and NOR (200 microM) with NADPH-supplemented microsomes for 30 min led to an approximate 30% decrease in spectrally apparent P450 content; the N,N-dimethylaminoalkyl drugs IMIP and AMIT did not significantly decrease apparent P450 content. Analysis of optical difference spectra of microsomes during NADPH-mediated metabolism of these drugs revealed a prominent increase in absorbance at 454 nm with DES and NOR but not IMIP or AMIT. Monospecific antibodies to the male-specific P450 2C11 and, to a lesser extent, P450 3A2 were effective in preventing the formation of the DES metabolite 454 nm-Soret peak. In addition, the 454 nm absorbance was not produced by the incubation of DES with NADPH-fortified hepatic microsomes from adult female or immature male rats. Studies with the steroid substrate testosterone, which undergoes P450-specific positional hydroxylation, indicated that P450 2C11 mediated 2 alpha- and 16 alpha-hydroxylation were most susceptible to the time dependent intensification of inhibition produced by DES (8.5 and 7.0 min preincubation required for loss of 50% activity, respectively) and NOR (4.0 and 4.0 min for loss of 50% of both activities). The 6 beta- (P450 3A2) and 7 alpha hydroxylase (P450 2A1) pathways were somewhat less susceptible to inhibition than 2 alpha- and 16 alpha-hydroxylation. These findings suggest that DES and NOR form a metabolite intermediate (MI)-complex, characterized by a Soret region absorbance maximum near 454 nm in the optical difference spectrum, with microsomal P450 in male rat liver in vitro. Studies with the steroid substrate testosterone as well as immunoinhibition experiments are consistent with the proposition that this MI complex forms principally with the male-specific enzymes P450 2C11 and 3A2. Although a human orthologue of P450 2C11 has not yet been identified, P450s of the 3A subfamily are quantitatively important enzymes in human liver. MI complexation of such enzymes could be a feasible underlying mechanism for certain clinically important drug interactions involving tricyclic antidepressants. PMID- 1599494 TI - A novel route of ATP synthesis. AB - Incorporation of the adenine moiety of 2'-deoxyadenosine (dAdo) into ATP, consistently observed in human erythrocytes, is a phenomenon which cannot be explained by the operation of any known pathway. We reported previously that this effect was not observed in adenine phosphoribosyltransferase-deficient erythrocytes showing that adenine must be an obligatory intermediate. However, generation of adenine from dAdo was difficult to reconcile with the operation of any known process in human cells, and involvement of S-adenosylhomocysteine hydrolase (SAH-hydrolase) was postulated. The present studies with intact human erythrocytes demonstrate that nucleoside analogues which inhibit SAH-hydrolase caused substantial attenuation of adenine transfer from dAdo into ATP. It was confirmed that dAdo is not a substrate of 5'deoxy-5'methylthioadenosine (5'MT adenosine) phosphorylase. Inhibition of the transfer of the adenine moiety of dAdo into ATP did not correlate with inhibition of 5'MT-adenosine phosphorylase by nucleoside analogues. This report provides further evidence that the pathway involving nucleoside (adenosine) analogue binding to SAH-hydrolase, release of base and subsequent phosphoribosylation can operate in intact cells. The metabolic significance of this process relates to the possible generation of free bases (adenine) in the human body, ATP synthesis and nucleoside drug interconversions. PMID- 1599496 TI - Time course of various inflammatory mediators during recurrent endotoxemia. AB - The time course of thromboxane B2 (TxB2), 6-keto-PGF1 alpha (stable metabolite of prostacyclin), tumor necrosis factor-alpha (TNF alpha), platelet activating factor (PAF), and interleukin-6 (IL-6) formation after three lipopolysaccharide (LPS) infusions was studied in pigs over an 18-hr, period. The Escherichia coli endotoxin W0111:B4 was injected i.v. into 10 of the test group pigs at a dose of 0.5 micrograms/kg over 30 min at 0, 5 and 10 hr of the experiment. Three pigs injected with physiological saline served as controls. At defined time points before and after each LPS administration venous blood was withdrawn (0, 15, 30, 45, 60, 120, 180 min) and plasma levels of TxB2, 6-keto-PGF 1 alpha, PAF, TNF alpha and IL-6 were determined. Pulmonary artery pressure (PAP) and cardiac output (CO) were measured every 15 min. TxB2 and PAF peaked significantly between 30 and 45 min, TNF alpha and 6-keto-PGF 1 alpha between 30 and 60 min, and IL-6 between 120 and 180 min after each LPS injection. The mediators PAF, TNF alpha and TxB2 showed a decreasing three-peak profile whereas 6-keto-PGF1 alpha exhibited an increasing one. IL-6 plasma concentrations increased after each LPS injection. The peak after the third LPS administration, however, was surprisingly low compared to the previous two. The first LPS infusion in our test group led to a significant, sustained rise in mean PAP. After recurrent LPS injections the peak in PAP was not as marked as after the first infusion, indicating the development of a tolerance towards LPS. Initially, CO showed hypodynamic values, whereas the end stage of the experiment was characterized by hyperdynamic CO levels. In conclusion, we believe this porcine model of septic shock to be one of the first large animal models to describe in detail the time-course of various important inflammatory mediators. PMID- 1599497 TI - Lipid peroxidation and irreversible damage in the rat hepatocyte model. Protection by the silybin-phospholipid complex IdB 1016. AB - IdB 1016 is a new silybin-phospholipid complex which is more bioavailable than the flavonoid silybin itself and displays free radical scavenging and antioxidant properties in liver microsomes. We report here that the addition of increasing concentrations of IdB 1016 to isolated rat hepatocytes caused a dose-dependent inhibition of lipid peroxidation induced by ADP-Fe3+ or cumene hydroperoxide. Moreover, IdB 1016 at the concentration which completely prevented MDA formation also protected isolated hepatocytes against the toxicity of pro-oxidant agents such as allyl alcohol, cumene hydroperoxide and bromotrichloromethane, without interfering with the activation mechanism of these xenobiotics. Similar protection was also obtained in hepatocytes prepared from animals pretreated in vivo with IdB 1016 while rat supplementation with pure silybin was totally inefficient. These results indicate IdB 1016 as being a potentially useful protective agent against free radical-mediated toxic liver injury. PMID- 1599498 TI - The influence of lipid peroxidation products (malondialdehyde, 4-hydroxynonenal) on xanthine oxidoreductase prepared from rat liver. AB - Depending on metabolic conditions, xanthine oxidoreductase acts as either a dehydrogenase (XDH) or an oxidase (XOD). The metabolism of hypoxanthine and xanthine by the oxidase is associated with the production of reactive oxygen radicals. Reaction of reactive oxygen radicals with polyunsaturated fatty acids (lipid peroxidation) leads to the formation of malondialdehyde (MDA) and 4 hydroxynonenal (HNE), known to modify proteins by reaction with NH2- and SH groups. Therefore, these aldehydes could influence both the activity of xanthine oxidoreductase and the XOD/XDH ratio. We found that incubation of xanthine oxidoreductase with MDA leads to an initial increase in XDH activity and to a continuous decrease in XOD activity, whereby the total activity decreases. This was in contrast to the effects of HNE which did not alter the XDH activity; XOD was however activated. This demonstrates that the lipid peroxidation products MDA and HNE are able to modify xanthine oxidoreductase similarly to a feed-back mechanism. PMID- 1599499 TI - Distinct induction profiles of three phenobarbital-responsive mouse liver cytochrome P450 isozymes. AB - The dose- and time-responses of three liver cytochrome P450 (P450) isozymes to 1,4-bis-[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP) and phenobarbital (PB) were studied in DBA/2 mice at activity, protein and mRNA levels. We found that the maximal induction ranged from about 3-fold (P4502a-4/5) and 5-fold (P4502c-x) to more than 50-fold (P4502b-10). Only P4502a-4/5 and associated mRNA displayed a biphasic time-response after TCPOBOP induction: a transient increase occurring 3 8 hr after administration with a subsequent decline at 24 hr before the maximal induction at 72 hr. The changes in P450 isozyme content reflected those in mRNA levels suggesting that the induction by TCPOBOP and PB is controlled largely at pretranslational stages. The isozyme P4502c-x and associated immunoinhibited benzphetamine N-demethylase and testosterone 16 beta-hydroxylase activities were induced half-maximally by 6-30 times smaller doses of TCPOBOP and by three to four times smaller doses of PB than isozymes P4502a-4/5, P4502b-10 or related activities. Furthermore, larger doses of TCPOBOP decreased the expression of P4502c-x to sub maximal levels. Our data show that the three isozymes, although all inducible by TCPOBOP and PB, have distinct dose dependencies and different time-responses to induction. This indicates that the induction by TCPOBOP and PB of P450s belonging even to the same subfamily may proceed by different mechanisms. PMID- 1599500 TI - Identification of the proximate peroxisome proliferator(s) derived from di (2 ethylhexyl) adipate and species differences in response. AB - Identification of the proximate peroxisome proliferator(s) derived from di (2 ethylhexyl) adipate (DEHA) has been achieved using primary hepatocyte cultures derived from different species and cyanide-insensitive fatty acyl CoA oxidase (PCO) as a marker enzyme for peroxisome proliferation. In rat and mouse hepatocytes, the parent compound (DEHA) had no effect on peroxisomal beta oxidation, but primary metabolites of DEHA, mono (2-ethylhexyl) adipate (MEHA) and 2-ethylhexanol (EH), were approximately equipotent in PCO induction (5-fold at 0.5 mM final concentration). The secondary metabolite of DEHA, 2-ethylhexanoic acid (EHA), was in both species the most potent peroxisome proliferator (25- and 9-fold induction in mice and rats, respectively, at 1 mM final concentration). At 2 mM final concentration a tertiary metabolite of DEHA, 2-ethyl-5-hydroxyhexan-1 oic acid, was less effective in mouse and rat hepatocytes at inducing PCO (15- and 5-fold, respectively). 2-Ethyl-5-oxohexan-1-oic acid and 2-ethylhexan-1,6 dioic acid had little effect (2-3-fold in both rat and mouse hepatocytes). Thus, EHA was identified as the proximate peroxisome proliferator of DEHA and mouse hepatocytes were approximately twice as sensitive as rat hepatocytes to peroxisome proliferation due to MEHA, EH and EHA. We investigated further species differences in response to peroxisome proliferators by using guinea pig and marmoset primary hepatocyte culture. None of the chemicals studied stimulated peroxisomal beta-oxidation in these species up to a final concentration of 2 mM. Higher concentrations lead to cytotoxicity. This lack of sensitivity of guinea pig and marmoset hepatocytes is in agreement with previous studies with di (2 ethylhexyl) phthalate metabolites, suggesting the absence of a threat of hepatocarcinogenic damage to these species and confirming that primary hepatocytes cultures are useful models for investigating the phenomenon of peroxisome proliferation. PMID- 1599502 TI - Effects of single and multiple increasing doses of vigabatrin on brain GABA metabolism and correlation with vigabatrin plasma concentration. AB - The effects of increasing (50-1600 mg/kg/day) doses of vigabatrin (GVG) both as single doses and after 8 or 28 days of treatment have been studied in 19 groups of 10 adult Wistar rats. The parameters studied were brain gamma-aminobutyric acid-transaminase (GABA-T) activity, GABA concentration and L-glutamate decarboxylase (GAD) activity. Single increasing doses of GVG progressively inhibited GABA-T activity, but a residual activity of about 40% was observed with the highest doses. GABA concentration increased in a dose-dependent manner but a ceiling was not reached. GAD activity was slightly inhibited at low doses and stimulated at high ones. When treatment was continued for 8 days, more marked effects of GVG on GABA-T and GABA, a more severe toxicity and higher GVG plasma concentrations were observed. GAD was inhibited instead of stimulated by high GVG doses. After 28 days of treatment the effects of GVG on GABA-T and GABA were similar to those after 8 days. However, toxic effects decreased and lower GVG plasma concentrations were found. IN CONCLUSION: (a) the more marked brain GABAergic effects observed after 8 days of treatment with GVG may explain the greater anticonvulsant effects observed by others in animals, and (b) GVG plasma concentrations correlate well with changes in brain GABA-T and GABA, and may partly explain changes in the effects of GVG related to the length of treatment. PMID- 1599501 TI - Menadione-mediated membrane fluidity alterations and oxidative damage in rat hepatocytes. AB - Menadione toxicity in isolated rat hepatocytes was mitigated by the antioxidant 4b,5,9b,10-tetrahydroindeno[1,2-b]indole at low concentrations (less than 100 microM), but not at high concentrations (greater than 200 microM) of menadione. When hepatocytes were incubated with menadione, there was a time-dependent and concentration-dependent inhibition of lipid peroxidation in intact cells, as well as an increase in the antioxidative potency of acetone extracts, suggesting that metabolites of menadione could inhibit oxidative stress, and that at high menadione concentrations a different mechanism was involved in cytotoxicity. A possible mechanism was suggested by the ability of acetone extracts from hepatocytes that had been incubated with menadione to increase osmotic fragility in red blood cells. This increase correlated with an increase in membrane fluidity in red blood cells, determined by flourescence polarization using the membrane probe 1,6-diphenyl-1,3,5-hexatriene. At 200 microM menadione, an increase in membrane fluidity was also observed in hepatocytes. The thiol dithiothreitol protected hepatocytes from 50 microM menadione toxicity, but not from greater than or equal to 100 microM menadione. The results suggest that while oxidative stress and arylation may be the critical mechanisms of toxicity at low menadione concentrations, at higher concentrations another mechanism such as enhanced membrane fluidity is operative. PMID- 1599503 TI - Induction of hepatic microsomal cytochrome P450 and drug-metabolizing enzymes by 4-benzylpyridine and its structurally related compounds in rats. Dose- and sex related differential induction of cytochrome P450 species. AB - We examined the abilities of 4-, 3- and 2-benzylpyridine and 4-tert-butylpyridine to induce hepatic microsomal cytochrome P450 and drug-metabolizing enzymes in male and female rats in order to define the effects of pyridine-containing compounds on drug metabolism. 4-Benzylpyridine (0.4 mmol/kg, for 2 consecutive days) induced total cytochrome P450 to about three times that of the controls at 24 hr, and its inducing effect was sustained for 120 hr after the treatment in male and female rats. 4-Benzylpyridine was a more potent inducer of cytochrome P450 than 3- and 2-benzylpyridine, which induced the cytochrome to 71.4 and 43.9%, respectively, of that produced by the 4-substituted isomer. 4-tert Butylpyridine also induced cytochrome P450. Immunoblot analysis revealed that a single treatment of male rats with 4-benzylpyridine at doses ranging from 0.05 to 0.80 mmol/kg induced cytochrome P450b/e and caused a maximum increase in the level of the isozyme at the 0.2 mmol/kg dose. 4-Benzylpyridine at doses from 0.40 to 0.80 mmol/kg also induced cytochrome P450c/d in male rats. In female rats, 4 benzylpyridine induced cytochrome P450b at doses ranging from 0.1 to 0.80 mmol/kg and produced a maximum increase in the level of this isozyme at 0.40 to 0.60 mmol/kg. Induction of cytochrome P450c/d by 4-benzylpyridine in female rats was observed at a dose of 0.20 mmol/kg, and the magnitude of the induction of the isozyme was increased in a dose-dependent manner. Both 3- and 2-benzylpyridine induced cytochrome P450b/e and/or c/d depending on the increase of total cytochrome P450 without changing the induction patterns of the isozymes. 4-tert Butylpyridine induced cytochrome P450b at doses ranging from 0.20 to 0.60 mmol/kg and slightly induced P450c/d at doses ranging from 0.10 to 0.40 mmol/kg in male rats. These results and our previous report (Matsuura et al., Biochem Pharmacol 41: 1949-1956, 1991) clearly show that the pyridine compounds having lipophilic groups at the 4- or 3-position of the ring could be inducers of cytochrome P450. The present results also revealed that 4-benzylpyridine shows dose- and sex related differences in the induction of cytochrome P450b/e and c/d in rats. PMID- 1599504 TI - Freezing action of a metabolite of haloperidol in frogs. AB - In vivo metabolism studies led to the identification of a previously proposed metabolite of haloperidol, 4-(4'-chlorophenyl)-4-piperidinol (CPPO), in the liver of a haloperidol-treated rat. However, the secondary metabolites of CPPO that we have proposed were not observed in this study. Neurotoxicity studies in frogs, which have been used to detect N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) action, showed that CPPO did not mimic the neurotoxicity of MPTP but caused a delayed and persistent freezing action in Rana pipiens frogs. It is proposed that this action may contribute to some of the delayed side-effects associated with haloperidol therapy. PMID- 1599505 TI - A multisubstrate mechanism of striatal dopamine uptake and its inhibition by cocaine. AB - A study of Na+ and Cl- as co-substrates in dopamine uptake into striatal suspensions and inhibition of dopamine uptake by cocaine was made by monitoring the initial velocity of the uptake of exogenously added non-radioactively labeled dopamine using a rotating disk electroanalytical technique with 50 msec resolution. Dopamine, in the concentration range of 0.025 to 4.00 microM, was found to be taken up rapidly into the tissue phase of striatal suspensions following the apparent zero order rate law for the first 25 sec. The observed, dopamine concentration-dependent, initial velocity data were first analyzed graphically using the Eadie-Hofstee transformation of the Michaelis-Menten kinetic equation and, subsequently, using all of the velocity data and the results of the graphical analyses, by non-linear curve fitting. Dopamine uptake was found to be first order in dopamine with a Vmax of 582 pmol/sec/g wet weight and a Km of 1.2 microM. The results of experiments in which choline and isethionate were substituted for Na+ and Cl-, respectively, suggested that the uptake process is second order in Na+ and first order in Cl-. Multisubstrate analyses of the initial velocities of uptake over the concentration range of 0.025 to 1.5 microM dopamine suggested that the mechanism of binding of dopamine to the uptake carrier is a partially random, sequential mechanism where dopamine or Na+ binds first with the uptake carrier and Cl- binds last. Cocaine was found to uncompetitively inhibit dopamine uptake and competitively inhibit both Na+ and Cl- binding (apparent Km values: 131 and 51 mM, respectively), suggesting that the mechanism of cocaine inhibition may be to bind to the dopamine occupied uptake carrier complex at the Na+ binding site. PMID- 1599506 TI - Monoclonal antibodies to rat liver microsomal cytochrome b5. AB - Hybridomas obtained by the fusion of spleen cells from rat cytochrome b5 immunized mice with mouse myeloma cells produced five groups of monoclonal antibodies (MAbs) with three mouse immunoglobulin subtypes: IgG1, IgG2b and IgM. All of the MAbs bound strongly to rat cytochrome b5 as measured by radioimmunoassay (RIA). Four clones of MAbs were also strongly immunoreactive with cytochrome b5 when tested by Western blotting, but only one of the MAbs (1 39-2) weakly immunoprecipitated cytochrome b5 in an Ouchterlony double immunodiffusion test. Two of the MAbs partially inhibited cytochrome b5-mediated NADH cytochrome c reduction catalyzed by liver microsomes (24-36%). Expression of immunodetectable cytochrome b5 was highest in the liver, next highest in the kidney, and quite low in the other tissues examined with MAb 1-17-1 by Western blotting. This MAb recognized homologous cytochrome b5 of human liver microsomes and in homogenates of TK- cells infected with recombinant vaccinia virus encoding human cytochrome b5. These MAbs to cytochrome b5 will be useful for the identification, quantification, and purification of cytochrome b5 from animal and human tissues, and for understanding its role in cytochrome P450 catalyzed drug metabolism and carcinogen activation with respect to tissue, organ and individual differences. PMID- 1599507 TI - Investigations on the hepatic uptake systems for organic cations with a photoaffinity probe of procainamide ethobromide. AB - Azido procainamide methoiodide (APM), a photolabile derivative of the transport model compound procainamide ethobromide (PAEB), shows a close resemblance to PAEB from a physicochemical point of view. Like PAEB it is effectively taken up by the liver and excreted into bile. Kinetics of the uptake of APM in isolated hepatocytes revealed that in addition to a non-saturable process, two saturable uptake systems are involved (Km1 = 3 microM, Vmax1) = 80 pmol/min/10(6) cells, Km2 = 100 microM, Vmax2 = 130 pmol/min x 10(6) cells). The uptake rate of APM was inhibited markedly in the presence of other organic cations. Organic anions and uncharged compounds generally had no inhibitory effect on the APM uptake. These results support the theory that there is a separate hepatic uptake system for organic cations like APM. Photoaffinity labeling of intact hepatocytes as well as plasma membrane sub-fractions enriched with sinusoidal domains disclosed two major binding polypeptides with apparent M(r) of 48,000 and 72,000. Such labeling patterns were not observed in membranes from hepatoma cells that are deficient in organic solute uptake. Differential photoaffinity labeling with other cationic compounds such as tributylmethyl ammonium and d-tubocurarine reduced the incorporation of APM in these polypeptides. The 48- and 72-kDa proteins might be involved in carrier-mediated transport of type I organic cations at the hepatic uptake level. PMID- 1599508 TI - Azoreductase activity by purified rabbit liver aldehyde oxidase. AB - Our laboratory has investigated the azoreduction of dimethylaminoazobenzene (DAB) and its analogs by hepatic microsomal cytochrome P450. We have extended these studies to the cytosolic fraction of the mammalian liver using the molybdoflavoenzyme, aldehyde oxidase. Purified rabbit liver aldehyde oxidase readily reduced azo dyes which are mainly water soluble and contain charged groups. Lipophilic azo dyes, although readily reduced by microsomal cytochrome P450, were either poor substrates or not reduced at all. Kinetic measurements revealed no relationship between Vmax and Km for all dyes. More extensive studies were conducted on four azo dyes, o-methyl, red, 2'-pyridyl-DAB, sulfonazo III and Orange II, with characteristic functional groups. With each of these substrates, azoreductase activity was greatest when 2-hydropyrimidine (2-OHP) was the electron donor compared to N1-methylnicotinamide (N-MN), propionaldehyde and butyraldehyde. With 2-OHP as the electron donor, o-methyl red and 2'-pyridyl DAB exhibited maximal activity at pH 5.0 while sulfonazo III and Orange II showed maximal activity at pH 9.5 and 7.0, respectively. Km values for o-methyl red and 2'-pyridyl DAB were lower at their pH optima whereas that for sulfonazo III was higher at its pH optimum. There was also no correlation between maximal activity and Km; apparently Km is not a primary determinant for activity. The degree of ionization of function groups depends on pH. Since highest activity is seen at that pH in which maximal ionization of the substrate occurs, it can be concluded that rate of reduction is at least partially dependent on the charged state of the substrate. Azoreduction was inhibited by menadione and SKF 525-A. Sensitivity to inhibition by menadione was greatest at the pH where 2-OHP exhibited considerably higher activity than N-MN, but no differential was seen at the pH where activities with the two-electron donors were similar. On the other hand, sensitivity of azoreductase activity to inhibition by SKF 525-A was the same irrespective of electron donor, indicating that the mechanisms for these two inhibitors were different. PMID- 1599509 TI - Inhibition of mast cell secretion by oxidation products of natural polyamines. AB - Mast cells secrete many biologically active compounds upon stimulation by immunoglobulin E (IgE) and specific antigen (Ag), anaphylatoxins, as well as a number of cationic compounds which include drugs, kinins and neuropeptides. The effects of the two naturally occurring polyamines, spermine (SP) and spermidine (SPD), on mast cell secretion were studied because they have been implicated in the modulation of cellular processes, possibly through their cationic charge or the regulation of calcium ions. SP and SPD over the range of 10(-7) to 10(-4) M inhibited the release of 5-hydroxytryptamine (5-HT, serotonin) triggered by compound 48/80 (C48/80) in a time- and concentration-dependent manner, as long as at least 2% calf serum (CS) was present. SP also inhibited secretion of both histamine and serotonin stimulated immunologically by using IgE and anti-rat IgE. This inhibition was not accompanied by cytotoxicity. The major available polyamine metabolites tested, N1-acetyl spermine (N1-acSP) and N8-acetyl spermidine (N8-acSPD), also showed inhibition in the presence of CS, whereas putrescine, N8,N1-hexamethylene-bis-acetamide (HMBA) and benzylamine did not. Fetal bovine serum (FBS), as well as human and rat serum, which do not contain polyamine oxidase, did not result in any inhibition with the polyamines tested. Inhibitors of the polyamine oxidase blocked the polyamine effect, indicating that the inhibition of mast cell secretion must derive from aldehydes produced from these polyamines. Addition of the aldehyde inhibitor phenylhydrazine (phi-HDZ), simultaneously with, but not following the polyamines, blocked their inhibitory effect, further strengthening the involvement of aldehydes. These results indicate that naturally occurring polyamines may regulate mast cell secretion through metabolic products of polyamine oxidase, a similar enzyme of which is also present in human liver, placenta and pregnant serum. PMID- 1599510 TI - Effects of sulfobromophthalein and ethacrynic acid on glyceryl trinitrate relaxation. AB - The effects of sulfobromophthalein (SBP) and ethacrynic acid (ECA), both inhibitors of glutathione S-transferase (GST), or glyceryl trinitrate (GTN) induced vasorelaxation were investigated in rabbit aortic strips. The aortic strips were pre-contracted with phenylephrine, followed by relaxation with 0.5 microM GTN, with or without 0.1 mM SBP or ECA. ECA was observed to inhibit GTN relaxation approximately 32%, whereas SBP did not alter the GTN activity. The dinitrate metabolites (GDN) of GTN in the tissues were also measured. The amounts of both GDNs were decreased in the ECA-treated, but not the SBP-treated group. Moreover, in the ECA-treated group, a strong correlation was obtained between the loss of GTN activity and the decrease in GTN metabolism. Concentration-response studies also revealed that ECA attenuates GTN relaxation. The slope factor of the concentration-response curves was decreased by ECA, but not by SBP, although both inhibitors caused a mild decrease in Emax. In the 9000 g supernatant of rabbit aorta, ECA was also observed to inhibit GTN metabolism more significantly than SBP. The results suggest that the mechanism of GTN activation may involve a GST isozyme that possesses high activities towards ECA. PMID- 1599511 TI - Effect of group-selective modification reagents on arylamine N-acetyltransferase activities. AB - Two forms of hamster hepatic arylamine N-acetyltransferase (NAT; EC 2.3.1.5), designated NAT I and NAT II, were purified 200- to 300-fold by sequential 35-50% ammonium sulfate fractionation, Sephadex G-100 gel filtration chromatography, AAB affinity chromatography, DEAE ion exchange chromatography, and P-200 gel filtration chromatography. Treatment of either NAT I or NAT II with N ethylmaleimide (NEM), a cysteine selective reagent, caused a concentration dependent loss of enzymatic activities. Acetyl coenzyme A (AcCoA) protected NAT I against inactivation by NEM, whereas both 2-acetylaminofluorene (2-AAF) and AcCoA protected NAT II against inactivation. Incubation of either NAT I or NAT II with phenylglyoxal (PG), an arginine selective reagent, caused a time-dependent and a concentration-dependent loss of both NAT I and NAT II activities; the inactivations followed pseudo first-order kinetics. The reaction order with respect to PG was approximately two for each enzyme, consistent with the expected stoichiometry for the reaction of PG with arginine. The presence of AcCoA provided full protection of NAT I against inactivation by PG. However, neither AcCoA nor 2-AAF provided protection of NAT II against inactivation by PG. Diethylpyrocarbonate (DEPC), a histidine selective reagent, caused time-dependent and concentration-dependent pseudo first-order inactivation of both NAT I and NAT II. Neither AcCoA nor products of NAT-catalyzed reactions protected NAT I and NAT II against inactivation by DEPC. These results suggest that cysteine, arginine and histidine residues are essential to the catalytic activity of both NAT I and NAT II; the cysteine(s) is located at or near the binding site of NAT I and NAT II, and the arginine residue appears to be located in the AcCoA binding site of NAT I. In contrast, the essential arginine residue(s) of NAT II and the essential histidine residue(s) of both NAT I and NAT II are not likely to reside in the binding site of the enzymes. PMID- 1599512 TI - Conversion of 5-iodo-2-pyrimidinone-2'-deoxyribose to 5-iodo-deoxyuridine by aldehyde oxidase. Implication in hepatotropic drug design. AB - 5-Iodo-2-pyrimidinone-2'-deoxyribose (IPdR) can be converted into 5-iodo deoxyuridine (IUdR), a clinical radiosensitizer, by aldehyde oxidase in the liver. This conversion does not require exogenous cofactors and cannot be catalyzed by mixed-function oxidases, xanthine oxidase or many other oxido reductases. This "IPdR oxidase" activity is enriched in the liver; thus, extensive conversion of IPdR to IUdR could be anticipated in the liver and the therapeutic index of IPdR could be better than that of IUdR as a radiosensitizer for primary liver cancers or tumors metastasized to the liver. Based on structure and activity relationship studies, nucleoside analogues which could be activated by this enzyme to compounds capable of inhibiting DNA synthesis could be designed and should be explored as agents against cancer, viruses or parasites in the liver. PMID- 1599513 TI - Evidence for stimulation of the K-Cl cotransport system by phenazine methosulfate. AB - The effects of phenazine methosulfate (PMS), a known generator of oxygen free radicals, on ion transport in human erythrocytes were studied. The treatment of the red blood cells with 0.1-0.8 mM PMS caused the concentration-dependent increase of K loss from the cells in K-free sodium chloride medium. The PMS dependent K efflux from the cells in oxygen-free medium, being in equilibrium with argon, did not differ from the control. After substitution of Cl- ions in the medium by NO3-, PMS caused only a small activation of K loss. PMS at a concentration of 0.8 mM was found to increase passive K transport in erythrocytes (ouabain-furosemide-resistant 86Rb influx) and at the same time to decrease active transport of K (ouabain-sensitive influx of 86Rb). Furosemide-sensitive cotransport of K was not affected by 0.8 mM PMS. The influx of 22Na in the red blood cells was also independent of the presence of 0.2-1.0 mM PMS in the bath medium. The results obtained suggest that PMS stimulated the reversible K-Cl cotransport in human erythrocyte membranes. This effect of PMS resembles the action of the well-known SH-alkylating agent, N-ethylmaleimide. PMID- 1599514 TI - The "anti-pyrimidine effect" of hypoxia and brequinar sodium (NSC 368390) is of consequence for tumor cell growth. AB - The rationale of the present study was to investigate the simultaneous effect of hypoxia and drugs with an "anti-pyrimidine effect" on tumor cell proliferation to evaluate putative changes in the sensitivity of cells to these kinds of chemotherapeutic treatment on reduced O2 tension. Pyrimidine de novo biosynthesis, at the stage of respiratory chain-dependent dihydroorotate dehydrogenase, was found to be a biochemical target site for oxygen deficiency as well as for Brequinar Sodium (6-fluoro-2-(2'-fluoro-1,1'-biphenyl-4-yl)-3-methyl 4-quinoline carboxylic acid sodium salt) (Brequinar). Increasing drug concentrations (0.1-50 microM) reduced the proliferation rate of in vitro cultured Ehrlich ascites tumor cells (IC50 = 0.25 microM). Decreasing concentrations of O2 reduced the proliferation rate (50% at approximately 3.5% O2). Brequinar at 2.5 microM stimulated the incorporation of exogenous [14C]uridine into RNA to 140 and 190% of controls, respectively, as a result of active salvage pathways, whereas it decreased the incorporation of [14C]NaHCO3 by the de novo pathway (to 20 and 5% of controls, respectively). Cells routinely grown in glucose-free, uridine-supplemented medium were resistant to 12.5 microM of the drug. The complete growth pattern of the tumor cells (increase in cell number and protein, RNA and DNA content of cultures during a 24-hr culture period) was examined (i) on reducing the O2 tension of the atmosphere stepwise from 20 to 1% O2; (ii) on addition of 0.125 microM Brequinar; and (iii) under both conditions. The combination was found to give an additive inhibitory effect under moderate hypoxia (5-20% O2) and a greater than additive effect if the oxygen tension was further reduced (1-5%). PMID- 1599515 TI - Conceptual biotransformation of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis retinoic acid and all-trans-retinoyl-beta-glucuronide in rat whole embryo culture. AB - In cultured rat conceptuses, intraamniotic microinjections of 2500 ng/mL of 4-oxo 13-cis-retinoic acid, 600 ng/mL 4-oxo-all-trans-retinoic acid or 4000 ng/mL all trans-retinoyl-beta-glucuronide, produce qualitatively and quantitatively similar patterns of dysmorphogenesis as those reported after the intraamniotic microinjection of 250 ng/mL all-trans-retinoic acid [Lee et al., Teratology 44: 313-323, 1991; Creech Kraft et al., Teratology 45: 259-270, 1992]. In the present study, we utilized HPLC techniques to analyze retinoid levels in cultured rat conceptuses, 1.5 hr after intraamniotic microinjections of 4-oxo-13-cis-retinoic acid (2500 ng/mL), 4-oxo-all-trans-retinoic acid (600 ng/mL) or all-trans retinoyl-beta-glucuronide (4000 ng/mL). Our findings show that, after the microinjections of 4-oxo-all-trans-retinoic acid or 4-oxo-13-cis-retinoic acid (at these selected concentrations), 4-oxo-all-trans-retinoic acid was predominant in the embryos proper at concentrations of about 200 nM. This was roughly equivalent to the levels of all-trans-retinoic acid assayed after microinjections of all-trans-retinoyl-beta-glucuronide (4000 ng/mL). We conclude from these studies that both 4-oxo-all-trans-retinoic acid and all-trans-retinoic acid behave as ultimate or proximate dysmorphogens. PMID- 1599516 TI - Effects of 1,25-dihydroxyvitamin D3 analogue 1,24(OH)2-22-ene-24-cyclopropyl D3 on proliferation and differentiation of a human megakaryoblastic leukemia cell line. AB - The novel analogue of 1,25-dihydroxyvitamin D3 (1,25(OH)2 D3), 1,24(OH)2-22-ene 24-cyclopropyl D3 (calcipotriol, MC903), exhibits similar effects on cell proliferation and cell differentiation in a newly established human megakaryoblastic leukemia cell line (HIMeg). MC903 was found to inhibit cell proliferation and induce cell differentiation in a liquid culture system at concentrations comparable to those of 1,25(OH)2 D3. Colony formation assay showed that MC903 or 1,25(OH)2 D3 markedly diminished the colony-forming ability of HIMeg cells at concentrations of 10(-6) M to 10(-10) M. Cell cycle analysis demonstrated that, as seen with 1,25(OH)2 D3, MC903 also altered the cell cycle distribution; the fraction of cells in G0 + G1 increased while those in S and G2 + M decreased. It can be concluded from these findings that 1,25(OH)2 D3 and its analogue MC903 have approximately equipotent effects on cells of megakaryoblastic lineage and are potentially useful in studying the cellular processes that are responsible for megakaryocytopoiesis. PMID- 1599517 TI - Multiple retinoid dehydrogenases in testes cytosol from alcohol dehydrogenase negative or positive deermice. AB - Retinoic acid syntheses from retinol by cytosol from testes of alcohol dehydrogenase negative or positive deermice were similar in specific activity and in their insensitivity to 1 M ethanol or 100 mM 4-methylpyrazole. Anion-exchange followed by size-exclusion chromatography revealed multiple and similarly migrating peaks in each cytosol that had both retinol and retinal dehydrogenase activities. Thus, the effects of ethanol on testes cannot be caused by direct inhibition of cytosolic retinoic acid synthesis because retinoid dehydrogenases distinct from mouse class A2 alcohol dehydrogenases, which corresponds to human class I, occurred in testes and they were not inhibited by ethanol. These data also demonstrate the occurrence of multiple cytosolic retinoic acid synthesis activities and indicate that the two reactions of cytosolic retinoic acid synthesis, retinol and retinal dehydrogenation, may be catalyzed by enzymes that occur as complexes. PMID- 1599518 TI - Effect of food on the bioavailability of low-dose methotrexate in patients with rheumatoid arthritis. AB - OBJECTIVE: To evaluate the influence of food on the bioavailability of an oral dose of methotrexate in patients with rheumatoid arthritis. METHODS: Methotrexate (15 mg) was given intravenously and orally, with or without a meal, to 10 patients. Blood samples were drawn at specific intervals to evaluate drug levels. RESULTS: Food reduced the peak concentration, from a mean of 0.71 mumoles/liter to 0.49 mumoles/liter (P less than 0.02), and slightly increased the time to peak concentration, from a mean of 1.3 hours to 2.0 hours. Bioavailability was highly variable (range 28-94%) but was not affected by food intake. CONCLUSION: Bioavailability of oral methotrexate shows marked interindividual variation but is not affected by the presence of food. PMID- 1599519 TI - Hair product use in systemic lupus erythematosus. A case-control study. AB - OBJECTIVE: We sought to determine if hair product use is associated with the development of systemic lupus erythematosus (SLE) and whether SLE patients who use hair products have more severe disease. METHOD: A questionnaire on hair product use was administered to 218 members of the Hopkins Lupus Cohort, 178 first- or second-degree relatives, and 186 best friends of the patients. RESULTS: There was no significant difference in exposure to hair dye or hair permanent in SLE patients before the diagnosis of SLE as compared with controls, nor were there any significant differences in measures of SLE disease activity in patients who used hair products after their diagnosis versus those who did not. CONCLUSION: Exposure to hair dyes and hair permanents is not associated with the development of lupus. No hair product is associated with SLE disease activity after diagnosis. PMID- 1599520 TI - Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. AB - OBJECTIVE: To standardize outcome measures in systemic lupus erythematosus (SLE). Three indices were identified which could adequately describe outcome (disease activity, damage from disease, and health status); we describe here the development of the Disease Activity Index. METHODS: Twenty-four variables were identified as important factors in a disease activity index. These were used to generate 574 patient profiles, which were rated on a disease activity scale of 0 10 by 14 rheumatologists. A second rating of 10 of the profiles yielded scores that were not significantly different from the first, indicating that experienced clinicians can reliably make global estimates of disease activity. Multiple regression models were used to estimate the relative importance of the 24 clinical variables in the physicians' global rating of disease activity. These were estimated on a "training set" of 75% of physicians' ratings, and then validated on a "testing set," consisting of the remaining 25% of physicians' ratings. RESULTS: The explanatory power of the models in the training set was high (R2 = 0.93). The models' regression coefficients for the organ systems were simplified for easier use in clinical practice. This generated a "weighted" index of 9 organ systems for disease activity in SLE, the SLEDAI, as follows: 8 for central nervous system and vascular, 4 for renal and musculoskeletal, 2 for serosal, dermal, immunologic, and 1 for constitutional and hematologic. The maximum theoretical score is 105, but in practice, few patients have scores greater than 45. The SLEDAI predicted well the physicians' ratings in the testing set (Pearson's correlation coefficients = 0.64-0.79). CONCLUSION: The SLEDAI is a validated model of experienced clinicians' global assessments of disease activity in lupus. It represents the consensus of a group of experts in the field of lupus research. PMID- 1599521 TI - Reactive fibromyalgia syndrome. AB - OBJECTIVE: To determine the frequency of a precipitating event occurring prior to the onset of fibromyalgia syndrome, in a consecutive series of patients. Outcome in patients in whom there was a causative factor was compared with that in patients with primary fibromyalgia. METHODS: Records of patients presenting over a 4-year period who fulfilled criteria for fibromyalgia were reviewed, and patients were classified as having reactive fibromyalgia if a specific event prior to the onset of illness could be identified. Outcome features, including employment status and disability compensation, were compared in patients with reactive fibromyalgia versus those with primary fibromyalgia. RESULTS: Twenty nine of 127 patients (23%) with a primary rheumatologic diagnosis of fibromyalgia reported having trauma, surgery, or a medical illness before the onset of fibromyalgia, and were classified as having reactive fibromyalgia. Patients in this group were more disabled than those with primary fibromyalgia, resulting in loss of employment in 70%, disability compensation in 34%, and reduced physical activity in 45%. CONCLUSION: The development of fibromyalgia after a precipitating event may represent the onset of a prolonged and disabling pain syndrome with considerable social and economic implications. PMID- 1599522 TI - Yersinia-triggered reactive arthritis. Use of polymerase chain reaction and immunocytochemical staining in the detection of bacterial components from synovial specimens. AB - OBJECTIVE: To investigate whether microbial DNA is present in synovial specimens from patients with Yersinia-triggered reactive arthritis. METHODS: Synovial specimens from 13 patients with Yersinia enterocolitica O:3-triggered reactive arthritis and from 16 control patients were studied using polymerase chain reaction and immunocytochemical staining techniques. RESULTS: Yersinia chromosomal DNA was not found in any of the synovial specimens from Yersinia triggered arthritis patients or controls, whereas with immunocytochemical techniques, Yersinia antigens were observed in synovial specimens from all of the patients with Yersinia-triggered reactive arthritis. CONCLUSION: Only stable bacterial degradation products, not whole bacteria, are present at the site of inflammation in Yersinia-triggered reactive arthritis. PMID- 1599523 TI - Anticentromere antibody as a predictor of digital ischemic loss in patients with systemic sclerosis. AB - OBJECTIVE: To determine the clinical and serologic risk factors for digital ischemic events in patients with systemic sclerosis (SSc). METHODS: Retrospective review of clinical and laboratory data and review of current clinical status of 98 patients with SSc, seen between 1985 and 1990. RESULTS: Amputation of 1 or more digits due to ischemia occurred in 20.4% of the patients; 9.2% had multiple digit loss. Sclerodactyly alone and anticentromere antibody (ACA) were associated with loss of 1 or more digits. Age, smoking status, duration of disease, or duration of Raynaud's phenomenon were not predictive for loss of digits. CONCLUSION: Patients with limited SSc who are positive for ACA have an increased risk of major peripheral vascular occlusive disease. PMID- 1599524 TI - Primary idiopathic pulmonary hypertension complicated by pulmonary arterial thrombosis. Association with antiphospholipid antibodies. AB - OBJECTIVE: We report an unusual case of primary pulmonary hypertension and review the pertinent literature. METHODS: A 25-year-old Caucasian woman presented with progressive dyspnea and was found to have pulmonary hypertension. Antiphospholipid antibodies were present. The patient had a prolonged hospital course, was unresponsive to therapy, and died suddenly. RESULTS: Postmortem examination revealed a large thrombus affecting the right main pulmonary artery, with plexogenic arteriopathy bilaterally. CONCLUSION: This appears to be the first reported case of primary pulmonary hypertension complicated by thrombosis of a main pulmonary artery in association with antiphospholipid antibodies. PMID- 1599526 TI - Eosinophilic fasciitis in a rhesus macaque. AB - Eosinophilic fasciitis (EF) is an inflammatory disorder in the category of scleroderma-like connective tissue diseases. There are no animal models for spontaneously occurring EF. We present the case of a rhesus macaque (Macaca mulatta) with clinical, laboratory, and histologic features of EF. PMID- 1599525 TI - Production of natural killer cell activity-augmenting factor (interleukin-6) by human epiphyseal chondrocytes. AB - OBJECTIVE: We sought to determine the capacity of human epiphyseal chondrocytes to modulate the cytotoxic activity of human natural killer (NK) cells by determining whether they release interleukin-6 (IL-6), a cytokine recently shown to stimulate NK cell activity. METHODS: Conditioned medium from human epiphyseal chondrocyte cultures (Ch-CM) was tested for IL-6 activity using the B9 cell hybridoma assay. Its NK cell-stimulating capacity in the presence of K562 (myelogenous leukemia) cells or human chondrocytes was evaluated in a 4-hour 51Cr release assay. Ch-CM-derived IL-6/NK cell-augmenting factor activity was partially purified by high-performance liquid chromatography (HPLC) gel filtration and Western blot. RESULTS: Ch-CM contained an NK cell-augmenting factor (NKAF) which was blocked by IL-2 or IL-6 antibodies. Ch-CM did not contain detectable IL-2 activity, but it stimulated IL-2 production by human peripheral blood lymphocytes (PBL). This IL-2-inducing capacity was inhibited by IL-6 antibodies, indicating that chondrocytes release an IL-6-like activity. Ch-CM significantly enhanced the proliferation of IL-6-dependent B9 hybridoma cells, and Western blot analysis of Ch-CM revealed specific bands corresponding to those of highly purified IL-6. Upon HPLC gel filtration, chondrocyte NKAF copurified with chondrocyte IL-6. Pure IL-6 and chondrocyte IL-6 were tested for their ability to stimulate the cytotoxic activity of human PBL against chondrocytes. Both mediators significantly enhanced chondrocyte killing. Lysis of chondrocytes by PBL was mediated by NK cells, since depletion of CD16+ cells resulted in inhibition of the activity. CONCLUSION: Thus, upon stimulation, chondrocytes produce IL-6 which, through IL-2 induction, augments the activity of NK cells against K562 target cells as well as against chondrocytes. PMID- 1599527 TI - Severe anemia associated with active systemic-onset juvenile rheumatoid arthritis successfully treated with recombinant human erythropoietin: a pilot study. PMID- 1599528 TI - Delay in the radiographic detection of sacroiliitis in ankylosing spondylitis. PMID- 1599529 TI - European health challenges. PMID- 1599530 TI - Further unmuddling of shunting, mixing, and streaming. PMID- 1599531 TI - Call for clarification of vitamin D recommendations. PMID- 1599532 TI - Antiasthma drugs and airway hyperresponsiveness. PMID- 1599533 TI - Pulse oximetry in closed limb fractures. PMID- 1599534 TI - Thiomolybdates in the treatment of Wilson's disease. PMID- 1599535 TI - Available tests for idiopathic intracranial hypertension. PMID- 1599536 TI - Secondhand tobacco smoke: early insights. PMID- 1599537 TI - Antiendometrial antibodies? PMID- 1599538 TI - Closing the chapter on Maharishi Ayur-Veda. PMID- 1599539 TI - Sterile needles: human immunodeficiency virus in diabetic intravenous drug users. PMID- 1599540 TI - Pneumothorax in the newborn. PMID- 1599541 TI - Nicotine gum in Tourette's disorder. PMID- 1599542 TI - Response of schizophrenic patients to benzodiazepines. PMID- 1599543 TI - Comments on the proposal to eliminate the organic mental disorders category in DSM-IV. PMID- 1599544 TI - Improving the American diet. PMID- 1599545 TI - Hairy cell leukemia: splenectomy after alpha-interferon therapy. PMID- 1599546 TI - Role of set-point theory in regulation of body weight. PMID- 1599547 TI - Comparative efficacy of cimetidine, famotidine, ranitidine, and mylanta in postoperative stress ulcers. PMID- 1599548 TI - The effect of 5-aminosalicylic acid on the mucosal immune system. PMID- 1599549 TI - Planned walking and communication in SDAT. PMID- 1599550 TI - Nursing homes and tranquilizer use among the institutionalized elderly. PMID- 1599551 TI - Infectious aneurysm of a mesenteric artery branch in a young patient. PMID- 1599552 TI - Rodent polyphyly? PMID- 1599553 TI - Uses of chlorhexidine in pin site care. PMID- 1599554 TI - Bulbourethral groups of Cowper's glands. PMID- 1599555 TI - Dural puncture and depth of the extradural space. PMID- 1599556 TI - 'Field' anaesthesia for an ICU procedure. PMID- 1599557 TI - Pain upon injection in the epidural space: common and unexplained. PMID- 1599558 TI - Mechanical versus manual ventilation of the lungs of infants in the operating room. PMID- 1599559 TI - Outpatient management of pyelonephritis. PMID- 1599560 TI - The decline of the history of surgery. PMID- 1599561 TI - Glasgow meningococcal septicemia prognostic score. PMID- 1599562 TI - Pulmonary hamartoma syndrome. PMID- 1599563 TI - Experience of invasive aspergillosis in Hong Kong. PMID- 1599564 TI - Retrobulbar anaesthesia. PMID- 1599565 TI - Transport of live animals for slaughter. PMID- 1599566 TI - Failure of exercise to reduce hypertension. PMID- 1599567 TI - Computer linkage of psychiatric emergency rooms. PMID- 1599568 TI - [Localized pleural fibrous mesothelioma (submesothelial pleural fibroma). Anatomo clinical study of 25 cases]. AB - We studied a retrospective series of 25 sub-pleural fibromas (benign localized pleural mesotheliomas) of which 23 where excised, collected over a period of 20 years. The current series confirms the excellent prognostic of these rare tumors. They are sometimes bulky, but not infiltrating and discovered by systematic chest X-ray. Modern imaging using CT-Scan and nuclear magnetic resonance can suggest their diagnostic which is confirmed by histopathologic analysis of the usually pediculate and easily removed tumor. Transthoracic needle aspiration is generally of little help for diagnosis. The histopathologic diversity of the tumor is rather confusing but characteristic features can be found with fusiform cells ans collagen stroma. Immuno-histochemistry is more helpful for diagnosis and histogenesis recognition than electron microscopy. PMID- 1599569 TI - [Oncocytic presentation of a primary epithelioid leiomyosarcoma of the liver]. AB - We report an epithelioid leiomyosarcoma of the liver with oncocytic differentiation. Initially misdiagnosed as an oncocytic endocrine tumor, analysis of the whole liver after transplantation permits rectification of the diagnosis. This observation outlines the fact that oncocytic differentiation is not restricted to epithelial cells but can also be encountered in cells of mesenchymal lineage. PMID- 1599570 TI - [Benign glandular schwannoma and Recklinghausen disease. Report of a case]. AB - The authors describe the case of a 32 year-old woman with a congenital neurofibromatosis referred for excision of a painful subcutaneous nodule of the left popliteal space. The histological study showed a tumor displaying a biphasic pattern made of fascicles of benign spindle cells admixed with mucinous epithelium. Immunohistochemistry (cytokeratin X, ECA X) and electron microscopy helped to prove the true epithelial nature of the glandular components. Glandular schwannoma has rarely been described, especially in a benign histological pattern; this one has never been reported in association with Von Recklinghausen's disease. The histogenesis of the glandular schwannoma remains uncertain. PMID- 1599571 TI - [Malignant intravascular lymphoma (malignant angioendotheliomatosis), with adrenal localization. Report of a case]. AB - A past history of epilepsy and terminal dementia in a fifty five year old patient lead to the post mortem diagnosis of malignant intravascular lymphoma (malignant angioendotheliomatosis). There was a scattered involvement of capillaries and venulae in leptomeninges, peripancreatic and perirenal adipose tissue, pericardium, myocardium. The only adrenal involvement was typically tumoral at macroscopic examination. Such a localization, often reported in B intravascular malignant lymphoma, is studied according to the recent publications of this entity. PMID- 1599572 TI - [Multiple granular cell tumor of the colon]. AB - With reference to a case of multiple colorectal granular cell tumors, the authors briefly review the literature concerning this unusual tumor localization. This case demonstrates the most common appendicular, caecal and rectal forms among the localizations of colonic granular cell tumors: as well as the possible proliferation of many other tumors especially in caecal localizations. However the course of the disease is slow, and at the present time only one case report of malignant colonic TCG has been published. PMID- 1599573 TI - [Spinal leptomeningeal tumor spread disclosing a pineocytoma]. AB - A 39-year-old female was admitted to the hospital because of a sudden meningeal syndrome followed by diplopia, cervical, dorsal and sciatic nerve pains, and right peripheral facial palsy. Cerebrospinal fluid obtained by lumbar puncture showed a protein level at 23 g/l. Myelography and magnetic resonance imaging (MRI) were in favor of a lumbar arachnoiditis. A meningeal biopsy revealed a tumour infiltration with foci of cells that were stained with anti-glial fibrillary acidic protein antibody. Cerebral MRI was performed to search for a central nervous system (CNS) primary tumour, and disclosed a pineal mass. Five months after the onset of the disease, the patient worsened her clinical state and died. Necropsy confirmed the presence of a pineocytoma with astrocytic differentiation and diffuse leptomeningeal spread. This exceptional occurrence leads us to discuss about primary tumours of the CNS with leptomeningeal spread. PMID- 1599574 TI - [Dermal nervous tumor with a combination of fusiform and granular cells. Neuroma or neurofibroma with granular cells?]. PMID- 1599575 TI - [Bilateral symblepharon. Conjunctival tuberculosis]. PMID- 1599576 TI - [Intra-abdominal desmoplastic round cell tumor in young subject]. PMID- 1599577 TI - [Is malignant mesenchymoma a mildly aggressive tumor?]. PMID- 1599578 TI - ["Sydney system". A new and original approach to gastritis]. PMID- 1599579 TI - [Lymphoid proliferation after organ transplantation]. PMID- 1599580 TI - [Bone hydatidosis. 12 cases]. AB - The hydatic cyst is a parasitic disease caused by the development in man of the larval form of echinococcus granulosus. All parts of the body may be involved, but the liver and lungs are the main locations of the disease. The bone site is rare, accounting for 0.9 to 2% of all hydatic lesions. Between 1982 and 1988, we have compiled 12 cases of hydatic disease of bone. They were located in the skull (4 cases), the iliac bone (4 cases), the omoplate (1 case), the ribs (1 case), the femur (1 case) and the fibula (1 case). These lesions are generally considered as primary, but association with visceral locations was noted in 3 cases in our series. PMID- 1599581 TI - HIV infection and AIDS in children. PMID- 1599582 TI - The health effects of low-level ionizing radiation. PMID- 1599583 TI - Occupational health concerns of firefighting. PMID- 1599584 TI - Biological interactions and potential health effects of extremely-low-frequency magnetic fields from power lines and other common sources. AB - Various different effects of ELF magnetic fields have been reported to occur at the cellular, tissue, and animal levels. Certain effects, such as the induction of magnetophosphenes in the visual system, have been established through replication in several laboratories. Many other effects, however, have not been independently verified or, in some cases, replication efforts have led to conflicting results. A substantial amount of experimental evidence indicates that the effects of ELF magnetic fields on cellular biochemistry, structure, and function can be related to the induced current density, with a majority of the reported effects occurring at current density levels in excess of 10 mA/m2. These effects, therefore, occur at induced current-density levels that exceed the endogenous currents normally present in living tissues. From this perspective, it is extremely difficult to interpret the results of recent epidemiological studies that have reported a correlation between cancer incidence and exposure to 50-Hz or 60-Hz magnetic fields with very low flux densities. The levels of current density induced in tissue by occupational or residential exposure to these fields are, in nearly all circumstances, significantly lower than the levels found in laboratory studies to produce measurable perturbations in biological functions. There is a clear need for additional epidemiological research to clarify whether exposure to ELF magnetic fields is, in fact, causally linked to cancer risk. Laboratory animal studies conducted under controlled conditions are also needed to determine whether ELF magnetic fields can initiate or promote tumors. In addition, more studies of both a theoretical and experimental nature are needed to elucidate the molecular and cellular mechanisms through which low-intensity magnetic fields can influence living systems. A growing body of evidence indicates that cell membranes play a key role in the transduction and amplification of ELF field signals. Elucidation of the physical and biochemical pathways that mediate these transmembrane signaling events will represent a major advance in our understanding of the molecular basis of magnetic field effects of biological systems. PMID- 1599585 TI - Worksite drug testing. PMID- 1599586 TI - Global immunization. The Expanded Programme on Immunization Team. PMID- 1599587 TI - Polio eradication from the Western Hemisphere. PMID- 1599588 TI - Health issues for college students. PMID- 1599589 TI - Mortality of American Indian and Alaska native infants. AB - Accurate determination of infant mortality rates among Indians in seriously hampered by variations in the identification of Indian persons and use of different subsets of the Indian population for various purposes. Lack of consistency in the reporting of racial origin on birth and death records is a source of substantial error. Because of these factors, more than the usual care must attend comparisons and inferences drawn from data in which these differences are present. At present, it would seem prudent to regard all data about American Indians as provisional. Even though Indian infant mortality remains higher than that for US all races, regardless of techniques used for estimates, the decline of Indian infant mortality by more than 80% since the establishment of the IHS is a truly remarkable achievement. This success has been ascribed to a combination of activities, including the provision of safe drinking water, especially as an integral part of the IHS program; the nearly universal immunization of Indian children; and emphasis upon comprehensive, community-oriented programs focused on maternal and child care. These successes have contributed to changes in the distribution of the leading causes of Indian infant mortality, so that the most prominent causes now are SIDS, congenital anomalies, injuries, and various infections. Because of these changes and advances in knowledge, the IHS has recently revised its five-year plan for dealing with infant mortality to provide greater attention to injuries and infections and has embarked upon a series of discussions with the American Academy of Pediatrics to address postneonatal deaths and the difficult problem of SIDS. Low socioeconomic conditions, so important in influencing mortality rates (7, 14, 29), have thus far proved to be intractable. In the meantime, success will depend upon ensuring optimal prenatal care, reducing those risk factors amenable to correction, and solving the problem of SIDS. PMID- 1599590 TI - The public health practice of tobacco control: lessons learned and directions for the states in the 1990s. PMID- 1599591 TI - Selected methodological issues in evaluating community-based health promotion and disease prevention programs. PMID- 1599592 TI - Depression: current understanding and changing trends. PMID- 1599593 TI - Social marketing: its place in public health. PMID- 1599594 TI - Unnecessary surgery. PMID- 1599595 TI - Causes of low preschool immunization coverage in the United States. PMID- 1599596 TI - Access and cost implications of state limitations on Medicaid reimbursement for pharmaceuticals. PMID- 1599597 TI - Acute confusional states in older adults and the role of polypharmacy. AB - Cognitive impairment resulting from drug therapy in older persons has been well documented for numerous classes of drugs. Unfortunately, the problem of ACS caused by polypharmacy is rarely reported in the medical literature, although we believe that it occurs frequently. Health professionals need more education concerning the risks of drug therapy in older persons and methods of reducing the use of multiple drug therapy. Finally, more research is needed to identify patient and drug factors that lead to drug-induced ACS and cognitive decline in the elderly. PMID- 1599598 TI - Cognitive impairment: dementia and Alzheimer's disease. AB - The importance of dementia, a syndrome of global cognitive impairment, has gained widespread recognition in the past two decades. The most common cause, Alzheimer's disease, may be the single greatest source of dysfunction among persons over age 85. The disease, distinct from normal aging, is progressive, has a highly variable course, and can have tremendous impact on families. Duration of symptoms averages eight to ten years from onset, four to five years from diagnosis. Diagnosis is often delayed, because of the insidious nature of the illness. Prevalence and incidence rates may vary severalfold between different studies. One consistent finding is the dramatic increase with age; prevalence rates are 25-48% for persons over age 85. The two most consistent risk factors for AD are age and positive family history. Another likely risk factor is head trauma. Alzheimer's disease is almost certainly due to heterogeneous causes. Biologic understanding of AD is primarily based on study of distinctive pathologic changes in the brain. Increasingly well-characterized pathologic changes precede the clinical manifestation of disease. Ultimately, the pathologic cause of AD is loss of neurons and neuronal connections in the brain, especially in the frontal and parietal association neocortex. Many systems are involved, but the most affected system is the cholinergic system, followed by the noradrenergic and serotonergic neurotransmitter systems. Drug treatment and other intervention strategies to prevent or delay progression of the disease have been limited, primarily because so little is known about the cause or risk factors for the disease. Current palliative treatments are attempts to minimize the morbidity of abnormal behaviors and medical complications associated with dementia. Ideally, treatment would either involve replacement therapy or drugs, which prevent or delay the pathologic changes that occur in AD. Two of the more promising experimental therapeutic attempts involve interruption of the pathogenetic events involving beta-amyloid and its precursor proteins and administration of NGF. Public health attempts at risk factor reduction are clearly premature. The next decade or two will likely witness improved understanding of the pathogenesis of Alzheimer's disease. Epidemiologic study will contribute to our knowledge of pathogenesis and may reveal heretofore unrecognized and, hopefully, modifiable risk factors. Social and clinical strategies to deal with a disease of such immense importance also needs development and evaluation. The public's interest in this disease is intense, and it looks to the scientific community for progress in understanding and managing this often tragic illness. PMID- 1599599 TI - Effects of physical activity on health status in older adults. II. Intervention studies. AB - This review has focused on a specific part of the relationship of exercise to health. The overall evidence supporting the health benefits of exercise is substantial and has been critically reviewed recently (18, 94). Thus, the United States Preventive Services Task Force recommends that all adults exercise regularly (94). The conclusions summarized below regarding older adults do not affect this basic recommendation. There is solid evidence that exercise can improve measures of fitness in older adults, particularly strength and aerobic capacity. These exercise effects occur in chronically ill adults, as well as in healthy adults. Because physical fitness is a determinant of functional status, it is logical to ask whether exercise can prevent or improve impairments in functional status in older adults. The evidence that exercise improves functional status is promising, but inconclusive. Problems with existing studies include a lack of randomized controlled trials, a lack of evidence that effects of exercise can be sustained over long periods of time, inadequate statistical power, and failure to target physically unfit individuals. Existing studies suggest that exercise may produce improvements in gait and balance. Arthritis patients may experience long-term functional status benefits from exercise, including improved mobility and decreased pain symptoms. Nonrandomized trials suggest exercise promotes bone mineral density and thereby decreases fracture risk. Recent studies have generally concluded that short-term exercise does not improve cognitive function. Yet the limited statistical power of these studies does not preclude what may be a modest, but functionally meaningful, effect of exercise on cognition. Future research, beyond correcting methodologic deficiencies in existing studies, should systematically study how functional status effects of exercise vary with the type, intensity, and duration of exercise. It should address issues in recruiting functionally impaired older adults into exercise studies, issues in promoting long-term adherence to exercise, and whether the currently low rate of exercise-related injuries in supervised classes can be sustained in more cost-effective interventions that require less supervision. PMID- 1599600 TI - Falls among older persons: a public health perspective. PMID- 1599601 TI - Nonfall injuries in older adults. AB - Nonfall injuries are an important cause of morbidity and mortality in older adults. In addition to the loss of life and human suffering, the economic costs and the changes in lifestyle are important aspects of the consequences of trauma. Rates of injury as a result of MVCs (occupant and pedestrian), suicide, and residential fire are higher in the younger and older segments of the population, as indicated by J-shaped or U-shaped curves. Domestic violence against older adults is a recognized, but not well investigated, problem. Although risk factors have been identified for some of the cause specific injuries, the continuation of epidemiologic research is important to elucidate risk factors, especially those for which interventions can be developed. The development, implementation, and evaluation of the intervention programs are necessary for a multifaceted approach to injury control in older adults. PMID- 1599602 TI - Public health assessment in the 1990s. PMID- 1599603 TI - How much physical activity is good for health? AB - Research studies over the past several decades confirm the health benefits of regular physical activity, a concept with foundations in antiquity. The effects of activity on certain individual health conditions, the precise dose of activity that is required for specific benefits, the role (if any) of intensity of effort, and the elucidation of biological pathways whereby activity contributes to health are topics for further research. Although details remain to be clarified, it is now clear that regular physical activity reduces the risk of morbidity and mortality from several chronic diseases and increases physical fitness, which leads to improved function. Table 3 outlines the relationship of activity to several diseases, a judgment on the strength of the evidence, and a rough determination of the amount of research extant. Results from clinical exercise studies and epidemiological investigations can be integrated into a consistent and coherent theory of healthful physical activity. However, some differences between these two research streams need to be reconciled. Exercise physiologists have generally recommended relatively intensive activity and a formal approach to exercise prescription. The epidemiological studies suggest a linear dose-response relationship, at least up to a point, between physical activity and health and functional effects. These data support public health recommendations directed toward the most sedentary and unfit stratum of the population and emphasize doing at least moderate physical activity. If this group of adults would accumulate 30 minutes of walking per day (or the equivalent energy expenditure in other activities), they would receive clinically significant health benefits. An important point is that it does not matter what type of physical activity is performed: Sports, planned exercise, household or yard work, or occupational tasks are all beneficial. The key factor is total energy expenditure; if that is constant, improvements in fitness and health will be comparable. There are probably 40 million adults in the US whose sedentary habits place them at considerably increased risk of morbidity and mortality from several diseases. These same individuals also are more likely to have functional limitations, especially as they move into the later years of life. The sizable independent relative risk for impaired health in sedentary persons, and the large number at risk, leads to a substantial public health burden. This problem deserves continued and increased attention by physicians and other health professionals, scientists, and the public health establishment. PMID- 1599604 TI - Molecular structure and dynamics of the four 10-hydroxynortriptyline isomers. AB - The three-dimensional structures, molecular conformations, and electrostatic potentials of the R-E-, S-E-, R-Z-, and S-Z-isomers of 10-hydroxynortriptyline were examined by computer graphics, molecular mechanical energy calculations, and molecular dynamics simulations in vacuo and in aqueous solution. Molecular models of the isomers, based on the structure of nortriptyline, were refined by energy minimization and used as starting points in the simulations. R-E- and S-Z-10 hydroxynortriptyline formed intramolecular hydrogen bonds between the side-chain nitrogen atom and the hydroxyl group during the simulations in vacuo, and had the side chain folded over the ring system in the minimum energy conformations. Intramolecular hydrogen bonding was not observed for R-Z- and S-E-10 hydroxynortriptyline, which had extended side chains in the minimum energy conformations and stronger negative molecular electrostatic potentials around the hydroxyl group than the R-E- and S-Z-isomers. PMID- 1599605 TI - Caffeine-induced behavioral stimulation is dose-dependent and associated with A1 adenosine receptor occupancy. AB - Caffeine's psychomotor stimulant effects may relate to its blockade of central adenosine receptors. We examined acute caffeine effects on motor activity, adenosine receptor occupancy in vivo, and receptor affinity and density ex vivo. Acute doses of caffeine-sodium benzoate (0, 20, 40, and 60 mg/kg, intraperitoneally [0, 0.10, 0.21, 0.31 mu mol/kg]) were given to CD-1 mice and their activity was measured in an animal activity monitor over a 1-hour period. Adenosine receptor occupancy in vivo was quantified in mice 1 hour postdosage, using the high-affinity, A1 receptor selective adenosine antagonist [3H]-8 cyclopentyl-1,3-dipropylxanthine. Adenosine receptor binding affinities and densities were determined from analyses of binding studies in cortical, hippocampal, and brainstem membranes from treated mice (0 and 40 mg/kg caffeine). Caffeine doses of 20 and 40 mg/kg, corresponding to mean brain concentrations of 5 and 17 micrograms/g, increased all horizontal and vertical motor activity measures and stereotypy counts, as compared to doses of 0 and 60 mg/kg. Additionally, all acute caffeine doses significantly altered specific A1 binding in vivo (decreasing binding between 55% and 73% versus vehicle), presumably as it occupied A1 receptors. Therefore, at doses of 20 and 40 mg/kg, caffeine stimulated motor activity as it occupied A1 receptors; at a dose of 60 mg/kg (mean brain concentration of 26 micrograms/g) caffeine had no stimulant effect even though it appeared to occupy A1 receptors. Acute caffeine dosage did not alter ex vivo adenosine receptor binding affinity or density in any brain regions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599606 TI - Effects of clozapine and thiothixene on glucose metabolic rate in schizophrenia. AB - Twelve patients with schizophrenia received positron emission tomography scans with 18F-deoxyglucose before and after 4 to 6 weeks of treatment with clozapine or thiothixene. Both stereotaxic and magnetic resonance image template methods were used to position regions of interest for metabolic rate analysis. Clozapine increased and thiothixene decreased metabolic rates in the basal ganglia; these effects were most marked on the right side. Within the basal ganglia, a superior to inferior gradient in drug effect was found for thiothixene but not clozapine. This gradient resembled in some respects observations on regional differences in D2 receptors in human autoradiography. Baseline metabolic rates also predicted clinical medication response, with right inferior caudate metabolic rates differentiating clozapine and thiothixene responders. Larger sample studies are needed to replicate and extend these initial findings. PMID- 1599607 TI - The growth hormone response to clonidine in acute and remitted depressed male patients. AB - The growth hormone (GH) response to clonidine was evaluated in 28 acutely depressed male patients, 17 remitted depressed patients, and 26 normal control subjects. The GH response to clonidine was blunted (delta less than 4 ng/ml) in a significantly increased proportion of both acute and remitted patients compared to control subjects. Covarying for age effects, the GH response to clonidine (as area-under-the-curve) was not significantly different between any of the three groups, but was significantly diminished in both the acute and remitted depressed patients who were ever hospitalized for an episode of depression, compared to control subjects. Six patients studied in both the acute and remitted states were blunted in both states. These findings could not be accounted for by other clinical and demographic variables including weight, time off antidepressants, severity of current depressive symptoms, and subtype of depression. These results raise the possibility that the blunted GH response to clonidine may represent a state-independent correlate of some forms of severe depression. Issues regarding the specificity and interpretation of this finding require further clarification. PMID- 1599608 TI - Clozapine and haloperidol have differential effects on glutamic acid decarboxylase mRNA in the pallidal nuclei of the rat. AB - The striatum, and one of its targets, the pallidum (globus pallidus and entopeduncular nucleus) are based ganglia nuclei involved in extrapyramidal movement control. Gamma-aminobutyric acid (GABA)ergic neurons of the pallidum may be important for the expression of the effects of agents which alter striatal neurotransmission. In this study, rats were treated once daily for 28 days with either haloperidol or clozapine, two drugs which respectively, do and do not, induce extrapyramidal movement disorders. In situ hybridization histochemistry was used to quantify the levels of labeling for the messenger ribonucleic acid encoding glutamic acid decarboxylase, the main synthesizing enzyme for GABA in neurons of the striatum, globus pallidus, and entopeduncular nucleus. Neither drug treatment altered levels of labeling in the striatum. Haloperidol treatment increased the level of labeling in the entopeduncular nucleus and clozapine treatment increased labeling in the globus pallidus suggesting that these drugs exert different regulatory effects on pallidal neurons. PMID- 1599609 TI - How distinct are the insulin and insulin-like growth factor I signalling systems? AB - Insulin and insulin-like growth factor I (IGF-I) are closely related peptides. Insulin is primarily involved in regulating carbohydrate, fat and protein metabolism. IGF-I, however, regulates growth and development of the whole organism as well as differentiated functions in specific tissues. Each of these functions are mediated by specific tyrosine kinase receptors expressed on the cell surface. The insulin and IGF-I receptors, though separate gene products, are very similar. Amino acid similarities range between 40 and 85% in different domains, the highest degree of homology being found in the tyrosine kinase domain. Tertiary structure similarities further explain the interactions of each ligand with the heterologous receptor; thus insulin receptors bind insulin with high affinity and IGF-I with lower affinity, and the opposite is true for the IGF I receptor. Since each ligand can stimulate both receptors and both receptors seem capable of mediating both metabolic and growth activities, what separates these two distinct physiological roles? The interaction of the ligands with their own specific high affinity receptors is facilitated by the presence of IGF specific binding proteins (BPs) which, however, do not bind insulin. These BPs, found both in the circulation and in tissues, bind all the circulating IGFs and transport the IGFs to their target tissues, thus ensuring that at physiological concentrations IGF-I will only interact with its own receptor. Furthermore, they modulate IGF effects. Since insulin circulates at much lower concentrations compared with the IGFs, this ensures that insulin will only interact with high affinity insulin receptors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599610 TI - How pyridoxal 5'-phosphate could function in glycogen phosphorylase catalysis. AB - A mechanism for the phosphorylase reaction is proposed which offers a plausible explanation for the essential role of pyridoxal 5'-phosphate in glycogen phosphorylases: in the forward direction, phosphorolysis of alpha-1,4-glycosidic bonds in oligo- or polysaccharides is started by protonation of the glycosidic oxygen by the substrate orthophosphate followed by stabilization of the incipient oxocarbonium ion and subsequent covalent binding to form alpha-glucose 1 phosphate. In the reverse direction, protonation of the phosphate of glucose 1 phosphate destabilizes the glycosidic bond and promotes formation of a glucosyl oxocarbonium ion-phosphate anion pair. In the subsequent step the phosphate anion facilitates the nucleophilic attack of a terminal glucosyl residue on the carbonium ion bringing about alpha-1,4-glycosidic bond formation and primer elongation. Both in the forward and reverse reactions, the phosphate of the cofactor pyridoxal 5'-phosphate acts as a general acid (PL-OPO3H- or PL-OPO3(2-) and protonates the substrate phosphate functioning as proton shuttle. Thus in glycogen phosphorylases, phosphates which directly interact with each other have replaced a pair of amino acid carboxyl groups functioning in catalysis of carbohydrases. PMID- 1599611 TI - Protein toxin inhibitors of protein synthesis. AB - Two classes of extremely toxic proteins kill eukaryotic cells by covalently modifying unique structural features of components that are essential for protein synthesis. Intoxication by these proteins results from the entry of a catalytic fragment into the cytoplasm. One class is typified by diphtheria toxin and Pseudomonas exotoxin A. The catalytic component of these toxins ADP-ribosylates and inactivates elongation factor 2 which is an essential participant in protein synthesis. This modification occurs at a unique post-translational histidine derivative, diphthamide, that is present in the ribosomal binding site of the elongation factor. The two toxins differ in their molecular organization but appear to possess identical reaction mechanisms and very similar active sites. The other class contains two types of toxins typified, respectively, by alpha sarcin, a member of a family of fungal toxins, and ricin, a member of a group of closely related plant proteins collectively termed ribosome-inactivating proteins. The catalytic components of the two types of toxins in this second class inactivate the large ribosomal subunit through two different hydrolytic alterations of 23-28S RNA. alpha-Sarcin and its congeners act as a specific endonuclease whereas ricin and its congeners act as a specific N-glycosidase. These hydrolytic cleavages occur at a pair of adjacent nucleotides within a highly conserved sequence near the 3' terminus of 23-28S RNA. The covalent integrity of this region of RNA is essential to elongation factor-dependent ribosomal functions and is located within the ribosomal binding domain of these factors. Both of these classes of toxins are being employed as 'magic bullets' to eliminate pathological cells. By combining the catalytic component of these toxins with various cell targeting components, useful and specific anticancer and immunomodulatory agents have been created. PMID- 1599612 TI - Riboflavin deficiency is associated with selective preservation of critical flavoenzyme-dependent metabolic pathways. AB - Riboflavin is a water soluble vitamin that serves as a precursor of flavin mononucleotide and flavin adenine dinucleotide. These two compounds are coenzymes in a variety of electron transfer reactions that occur in energy producing, biosynthetic, detoxifying and electron scavenging pathways. When an organism is confronted with inadequate dietary riboflavin, characteristic changes occur in the cellular distribution of the various flavin fractions as well as in the activities of flavin-dependent enzymes. These changes suggest a specific hierarchic response to riboflavin deficiency, e.g. the core electron transfer chain required for ATP synthesis is preserved while the enzymes required for the first step of fatty acid beta-oxidation are diminished. The mechanisms by which the specific changes in enzyme activity are mediated have not been completely identified, but appear to result from a combination of diminished access of normal or near normal levels of apoenzyme to coenzyme and diminished abundance of apoenzyme. The changes in apoenzyme content potentially result from alterations in either protein stability or gene expression. The response to riboflavin deficiency of several key enzyme systems and the pathways affected will be discussed and a hierarchic order by which specific enzyme activities are preserved while others are decreased will be proposed. The current understanding of the molecular mechanisms by which these changes are mediated will be discussed. PMID- 1599613 TI - 31P-NMR of free and protein-bound molybdopterin guanine dinucleotide. AB - Molybdopterin guanine dinucleotide was studied by 31P-NMR in the free, iodoacetamide derivatized form [di(carboxamidomethyl)molybdopterin] and in the native state in the dimethyl sulfoxide reductase from Rhodobacter sphaeroides. The spectra confirm the presence of a pyrophosphate moiety in the cofactor molecule. Comparison of the spectrum of the free pterin with that of the protein bound cofactor reveals a substantial upfield shift of the 31P resonances in the enzyme-bound form with respect to the free form. This shift is attributed to differences in the bond and torsional angles of the phosphates. The spectrum of the protein suggests significant coupling between the two phosphorus nuclei with coupling constants of approximately 200 Hz. Comparison of the 31P-NMR spectra of molybdopterin guanine dinucleotide and flavin adenine dinucleotide suggests that the two cofactors have similar conformations in both their free and protein-bound forms. PMID- 1599614 TI - Synthesis of fluoro- and hydroxy-derivatives of vitamin K as substrates or inhibitors of the liver microsomal vitamin K-dependent carboxylase. AB - The rat liver microsomal vitamin K-dependent carboxylase catalyzes the carboxylation of glutamyl to gamma-carboxyglutamyl residues in the presence of reduced vitamin K, O2 and CO2. The specificity of the enzyme for the vitamin substrate has been probed by the synthesis of a series of fluoro- hydroxy- and methoxy-analogs. 2-Fluoro-methyl-3-phytyl-1,4-naphthoquinone and 2-methyl-3-(1' fluorodecyl)-1,4-naphthoquinone were synthesized but found to be unstable under enzyme assay conditions. The reduced (naphthohydroquinone) forms of 2-hydroxy methyl-3-phytyl-1,4-naphthoquinone, 2-methoxymethyl-3-phytyl-1,4-naphthoquinone and 2-methyl-3-(1'-hydroxy-decyl)-1,4-naphthoquinone were inactive as substrates, but inhibitors of the enzyme. The two hydroxy analogs were shown to be low Ki (less than 10 microM) inhibitors of the reduced 2-methyl-3-phytyl-1,4 naphthoquinone-dependent activity of the enzyme. The oxidized forms of these compounds did not inhibit the enzyme and they had no activity as in vivo anticoagulants. PMID- 1599615 TI - [Problems and eradication of Ambrosia artemisiifolia L. in Quebec in the urban and suburban environments]. AB - Ambrosia artemisiifolia is a common weed in Canada and it is one of the most important source of aero-allergenic pollen in the north-eastern part of North America. It is a problem mostly along roads in urban or suburban areas. It is easily controlled by herbicides but their use is increasingly restricted because of environmental considerations. Therefore, new methods must be developed to control this weed. Three types of controls were evaluated against Ambrosia artemisiifolia along an expressway in the summer of 1990. The control methods were hand weeding, mowing at 2 cm, 5 cm, or 8 cm, and crushing by a roadroller. These treatments were done at different dates in the course of the summer. Hand weeding was the most effective in reducing pollen and seed production although it was also the most expensive. Mowing was very effective when it was done at a height of 2 cm from the soil. It is the only height at which seed production was significantly reduced. Mowing efficacy in reducing pollen production tended to decrease with the raising of the mowing blade. The efficiency of weed pulling or moving improved when they were performed later in the growing season. Crushing was not an effective method of control. Mowing or hand weeding cannot eradicate Ambrosia artemisiifolia but if they are consistently used, they could reduce its population level over several years by decreasing seed production. The treatments either eliminated pollen production or reduced it at least by 88%, thereby insuring a relative relief for people allergic to the pollen of this plant. PMID- 1599616 TI - [Concentration of ragweed pollen and prevalence of allergic rhinitis in 2 municipalities in the Laurentides]. AB - In the province of Quebec, ragweed pollen is the principal allergen causing allergic rhinitis. The present study examines the relationship between the concentration of ragweed pollen and the prevalence of allergic rhinitis in August in the populations of two municipalities in the Laurentide area, a region on the northern limit of distribution of ragweed. The concentration of ragweed pollen was measured with a Burkhard sampler. The prevalence of allergic rhinitis was simultaneously measured by a telephone survey which was addressed to a random sample of 500 households in the two municipalities. The results showed a significant difference in the prevalence rate of allergic rhinitis in the population of the two municipalities (3,77% and 7,22%) exposed to significantly different pollen levels. Interventions aimed at lowering the pollen concentrations could lower the prevalence rate of allergic rhinitis in August. PMID- 1599617 TI - [Biological and clinical prevalence of pollinosis caused by ragweeds of the upper valley of the Rhone corridor]. AB - An epidemiological study of ragweed allergy was conducted on 646 employees belonging to 6 factories located in the Rhone valley south of the city of Lyon. Information on seasonal evocative clinical symptoms was obtained through a self administered questionnaire. Biological prevalence was assessed by measuring anti ragweed IgE specific antibodies. Measurements were performed by immunoenzymatic assay (W1 Phadezym RAST from Pharmacia). 34 (5,4%) subjects had evocative symptoms whereas 37 (5,9%) had increased specific IgE. Persons with the highest IgE levels were symptomatic. Concordance between symptoms and biology was 35% (12/34). Results indicate that sensitization level varies according to the location of the factory and people's residence, the risk to become allergic being of 10% in the most exposed population. This data emphasize the need to promote anti-ragweed eradication policy. PMID- 1599618 TI - [Demand and costs of medical care according to age and sex among the insured members of the Medical Association Assistance Center of Uruguay]. AB - This study analyzes the demand and use of medical services in terms of age and sex for outpatient care and hospitalization provided to the 272,000 members of the Medical Association Assistance Center in Uruguay, a prepaid nonprofit insurance plan. Individual records were organized into annual usage by five-year age groups and reveal that use of services--consultations, drugs, and hospitalization--increases exponentially after the age of 50. Women utilize from 15% to 41% more services than men. The cost of services shows the same trend. For those over 84 years of age, this cost is US$598 per year, with an average institutional cost of US$166. The study also quantifies differences in risk by age and sex and draws conclusions regarding price and admission policies for new members of collective medical care institutions, which in July 1990 covered 51% of the Uruguayan population. PMID- 1599619 TI - [Concepts about AIDS among the adult population of Managua]. AB - Nicaragua has the lowest prevalence of AIDS in Central America. In other countries where AIDS is more prevalent, the first epidemic of asymptomatic infections with human immunodeficiency virus (HIV) and the second of clinical cases of AIDS have been followed by a third epidemic of fear and discrimination. In December 1989 a study was conducted to investigate knowledge and attitudes about AIDS in a sample of 287 adults in Managua. Most of the interviewees had heard of the disease from newspapers and television, and more than 90% understood how HIV was principally transmitted. However, between one-third and one-half the interviewees believed that HIV could be transmitted by causal contact such as kissing (53%) or by mosquito bites (49%). In addition, the majority considered that isolation of HIV-infected persons and control of immigration into the country would be effective measures for preventing the spread of the disease. These results are similar to findings from studies carried out in other countries of Latin America where the HIV and AIDS epidemics started much earlier. This would suggest that the so-called "third epidemic" of discrimination and fear is affecting Nicaragua in advance of the other two. PMID- 1599620 TI - Ethanol decreases the velocity of spike propagation along a fast motor axon. AB - Intracellular recordings were made from the fast bender excitor motor axon in autotomized crab limbs bathed in normal saline, and in salines made with up to 240 mM of ethanol. The presence of ethanol reduced the amplitude, the rise time and the decay time of the evoked action potential, and decreased the velocity at which the spike was conducted down the axon. There was a linear relationship between each of these four parameters and the concentration of ethanol in the saline. The close relationship between spike rise time and conduction velocity suggests that ethanol slows the rate of membrane depolarization by the spike and thus decreases the velocity at which action potentials are propagated along the axon. PMID- 1599621 TI - Role of context in ethanol tolerance and subsequent hedonic effects. AB - Two groups of male Sprague-Dawley rats received ethanol dose-effect tests for FR30, food-reinforced operant performance, in each of two environmental contexts, before and after a period of daily presession ethanol or saline injections. During the latter period, context alternated daily. The ethanol group received ethanol prior to sessions for one context and saline, prior to sessions for the other context. The saline group always received presession saline. The ethanol, but not the saline, group displayed robust tolerance to ethanol's rate-decreasing effects, with no difference between tests in each context. Both groups then received training and testing in an ethanol-conditioned place preference task. The saline group displayed significant avoidance of the compartment paired with ethanol. The ethanol group displayed no initial aversion for the ethanol compartment and, with extended conditioning, showed a significant increase in time spent in the ethanol compartment. We suggest that this tolerance represents context-independent, learning to compensate for ethanol-induced effects, and that this tolerance subsequently blocked the conditioned place aversion evident in nontolerant controls, thereby enhancing the estimates of ethanol's reward properties. PMID- 1599622 TI - Ethanol-produced interoceptive stimuli are time dependent in selectively bred HAS and LAS rats. AB - Fourteenth generation high alcohol-sensitive (HAS) and low alcohol-sensitive (LAS) rats were trained to discriminate the effects of 600 mg/kg intraperitoneally administered ethanol from its vehicle at 6 and 30 min postadministration. Each of the earlier- and later-trained animals were given lower doses of ethanol and ED50 values at their trained postadministration interval were found to be nonsignificantly different. Thus, there was no difference between HAS and LAS animals as to their sensitivity to the discriminative effects of ethanol. Phase-generalization studies, where rats trained at 6 min postadministration were tested with the drug at 30 min postadministration were shown not to generalize, whereas the animals trained at 30 min postadministration and tested at 6 min postinjection were shown to readily discriminate the discriminative stimuli. This asymmetrical generalization lends evidence to the biphasic action of ethanol, and suggests that the earlier phase is quantitatively different than the latter phase. The similarity in sensitivity of the LAS and HAS animals, furthermore, suggests that the discrimination of ethanol is not based on its hypnotic effects. PMID- 1599623 TI - Bombesin reduces alcohol choice in nutritive expectancy and limited-access procedures. AB - Bombesin is a bioactive tetradecapeptide found in nerves of the brain and gut and previously shown to inhibit intake of ethanol in forced-choice, one-bottle tests in water-deprived rats. In the present experiments, intraperitoneal bombesin (4 100 micrograms/kg) reduced selection of alcohol in two-bottle choice tests with water. In an application of the "nutritive expectancy" procedure, weight-reduced rats received access to 4% w/v ethanol and water. Bombesin injection suppressed the intake of ethanol, but not of water, in rats with prior ethanol experience. In an application of the "limited access" procedure, nondeprived rats received access to 6% w/v ethanol and water in nonhome cages during either the light or the dark phase of a 12:12 h lighting cycle. Bombesin injection lowered the intake of ethanol, but not of water, in both phases of the lighting cycle and in both sexes. Water deprivation is not necessary for bombesin to inhibit alcohol intake and this effect cannot be explained by hypodipsia, nonspecific debilitation, or conditioned aversion. Endogenous bombesin-like neuropeptides may specifically reduce choice of alcohol by signaling satiation with ethanol. PMID- 1599624 TI - Alcohol and heat tolerance in warm-acclimated rats. AB - The effect of chronic ethanol intake and warm acclimation on the heat tolerance of rats under the influence of alcohol was studied. The animals were divided into two groups: Group 1 received water as their fluid intake and, group 2 received a 10% ethanol solution, and both groups were exposed to a temperature of 30 degrees C for 4 weeks. Excretion of urinary catecholamines was measured prior to warm exposure at 22 degrees C and once a week during warm exposure at 30 degrees C. After warm acclimation a dose of alcohol 2 g/kg was injected in the rats intraperitoneally (i.p.), and then they were exposed to a heat stress of 40 degrees C for 45 min. During warm acclimation, the controls consumed more fluid and they excreted more norepinephrine into the urine than the alcohol-fed animals during the first week. After the period of acclimation there were no significant differences in urinary excretion of catecholamines between the groups. Colonic temperature of the controls was 0.7 degrees C higher than in the alcohol-fed animals. Acute alcohol administration (2 g/kg) increased the colonic temperature of the alcohol-fed animals during a heat stress of 40 degrees C more than in the controls. After heat stress, the concentration of catecholamines in the blood was significantly higher in the controls. The results show that the hyperthermic effect of ethanol was more considerable in the rats whose drinking water during warm acclimation was an ethanol solution. PMID- 1599625 TI - Lifetime prolongation in voluntary alcohol-consuming rats (SHR) treated with clofibrate. AB - Clofibrate affects lipid and alcohol as well as drug and eicosanoid metabolism. Spontaneous hypertensive rats (SHR) further increase their high voluntary alcohol consumption during clofibrate feeding. The interaction of alcohol and clofibrate was studied in two long-term trials. Seventy-nine male SHR (aged 27 weeks) were offered increasing concentrations of ethanol, up to 30% (tap water ad lib), and 3 months later 0.5% clofibrate-food. Four groups were established: N, normal controls; NA, standard diet+alcohol; C, clofibrate feeding; and CA, clofibrate feeding + alcohol. Food intake, alcohol consumption, body weight, and laboratory values were recorded continuously. Life duration (weeks) after the start of the trial was 63.3 +/- 3.3 in N, 73 +/- 2.6 in NA, 77.7 +/- 4.3 in C, and 90.3 +/- 2.8 in CA. There were no alcohol-related liver findings in NA and CA. Most of the animals died of cardiac and renal failure. An increase of tumors in clofibrate treated rats was not observed. Voluntary alcohol consumption or clofibrate feeding significantly lengthens lifetime, which is prolonged by 42% if ethanol is combined with clofibrate. This is obviously not mediated by the lipid lowering effect or an influence on body weight and blood pressure of either clofibrate or alcohol. PMID- 1599626 TI - The acute dose-related effects of ethanol on right ventricular function in anesthetized dogs. AB - The acute dose-related effects of small to moderate doses of ethanol on right ventricular functioning were studied on 18 anesthetized, artificially ventilated dogs in 39 sessions. Diluted ethanol (from 25-37.5%) was infused during 40 minutes, yielding total doses of 1.0 g/kg (n = 15), and 1.5 g/kg (n = 12) with corresponding venous blood ethanol peak concentrations of 1.38 +/- 0.25 and 2.41 +/- 0.31 mg/ml, respectively. Heart rate increased up to 16% in groups receiving ethanol. In the control group receiving the equivalent volume of saline (n = 12) heart rate decreased 14%. Pulmonary arterial systolic pressure increased from 24 +/- 3 to 27 +/- 3 mmHg and diastolic pressure from 11 +/- 2 to 14 +/- 4 mmHg (p less than 0.05) when the ethanol dose was 1.0 g/kg. The pulmonary arterial resistance increased from 620 +/- 135 to 805 +/- 185 dyn.s.cm-5 (p less than 0.01). The peak dP/dt decreased maximally by 20% with increasing ethanol doses. Stroke volume decreased maximally by 14% but due to the increase in heart rate, cardiac output even increased. The changes in end-diastolic volume and pressure were not significant. Hence, the ethanol increased heart rate and afterload of the right ventricle but depressed the myocardium. PMID- 1599627 TI - Taste preferences in rat lines selected for low and high alcohol consumption. AB - Alcohol-avoiding (ANA), alcohol-preferring (AA), and control Wistar rats were tested sequentially for their initial preferences for single concentration solutions of quinine, saccharin, salt, and citric acid, and then for an ascending series of saccharin concentrations. A similar study was subsequently conducted with the alcohol-nonpreferring (NP) and alcohol-preferring (P) rat lines. Both lines developed for low alcohol consumption drank much less saccharin than their respective lines developed for high alcohol intake when tested with the single concentration and with the ascending series. The ANAs also generally drank less of the bitter, salty, and sour solutions than the AAs or Wistars but little difference was found between the NPs and Ps with the other tastes. The curve relating saccharin consumption to concentration reached a maximum at about the same concentrations for AAs, Wistars, NPs, and Ps but for the ANAs, was shifted to the left. The results support a close relationship between the genetic factors influencing alcohol and saccharin intake in both line pairs. This relationship is probably not caused by saccharin tasting like alcohol to a rat, because other results indicate that the NPs do not have more negative reactions initially to the taste of alcohol, but it might be related to similar mechanisms mediating the reinforcement from sweet tastes and from systemic alcohol. PMID- 1599628 TI - Ethanol exposure affects trophic factor activity and responsiveness in chick embryo. AB - Chick embryos were chronically exposed to either ethanol (approximately 30 mg/d) or saline, from E4-E13. Homogenate extract was prepared from forebrain tissue from E16 experimental and control embryos and was applied to cultured dorsal root ganglia (DRG). Neurotrophic activity in the forebrain extract (FBX) was significantly reduced in the ethanol-treated embryos compared to saline controls, both in terms of influences on neuronal survival and process elaboration. In addition, E8-9 DRGs from embryos exposed to ethanol from E4 were less viable in the presence of NGF than were those from controls. DRG survival in the presence of E16 FBX (from untreated embryos) was not different following ethanol treatment, but neurite production was significantly reduced. These results suggest that neurotrophic factor content and responsiveness may be appreciably altered following chronic prenatal ethanol exposure. Such alteration could underlie certain CNS anomalies seen in the fetal alcohol syndrome. PMID- 1599629 TI - Ethanol tolerance developed during intoxicated operant performance in rats prevents subsequent ethanol-induced conditioned taste aversion. AB - Four groups of Sprague-Dawley rats (n = 10 per group) were trained in a two-phase conditioning experiment. All rats were initially trained in an FR30 operant task (phase 1), and subsequently trained in a conditioned taste aversion (CTA) task. The groups of rats differed in their ETOH exposure. All rats received 2-week chronic exposure in phase 1. Two groups received chronic presession ETOH and, therefore, the opportunity for intoxicated practice; another group, yoked to this latter group, received postsession ETOH; the final group received presession saline injections. The presession ETOH groups were conditioned in the CTA task with either ETOH or saline; both increased their intakes of the conditioned tastant. The presession saline and the postsession ETOH groups received ETOH CTA; both developed a robust CTA. Thus, prior history of intoxicated practice under the operant task prevented the development of ETOH-induced CTA. We argue that ETOH exposure may be a necessary but not sufficient condition for tolerance to develop to the aversive attributes of ETOH. PMID- 1599630 TI - Effects of nicotine and ethanol on rat atrial membrane potentials. AB - The purpose of this research was to study the effects of nicotine and ethanol, alone and in combination, on cardiac membrane potentials (MP). Rat atrial preparations driven at 5 Hz were superfused with Tyrode's solution (37 degrees C) while recording MP with intracellular microelectrodes. Nicotine concentrations below and including 6.2 x 10(-5) M did not affect MP. Within 15 s, nicotine 3.1 x 10(-3) M shortened the action potential duration (APD) and depressed the overshoot of the action potential (OS). This action was blocked by atropine. After 3 min, nicotine prolonged the APD and depressed Vmax of phase O, OS and the amplitude of the action potential (AAP), without affecting the resting membrane potential (RMP). Nifedipine blocked the depression of the OS while tetraethylammonium chloride blocked the prolongation of the APD. Acute exposure to ethanol depressed OS and AAP and shortened APD, but it did not affect RMP or Vmax of phase O. When nicotine and ethanol were administered simultaneously, the APD-prolonging effects of nicotine prevailed. The influence of chronic ethanol ingestion on the acute action of nicotine and/or ethanol was studied in rats pair fed a liquid diet with (ER) or without (NR) ethanol (35% of total caloric intake) for 24 weeks. Chronic ethanol ingestion accentuated the depressant effect of nicotine 3.1 x 10(-3) M on OS and AAP, but it did not modify the APD-prolonging action of nicotine. The same results were observed when ER and NR were exposed to nicotine and ethanol simultaneously. PMID- 1599631 TI - Effect of ethanol administration on plasma glycerol levels in the rat. AB - Many mechanisms have been postulated as being responsible for the fatty liver resulting from ethanol ingestion. Lipid mobilization has been strongly implicated in both acute and chronic ethanol administration--the difference between the two lying in the source of the fat. In the acute situation, the lipid is mobilized from depot fat, whereas in the chronic situation, it apparently comes from the diet. One possibility not explored is the mobilization of glycerol. This substance is the backbone of triglyceride. Hence, an influx of glycerol to the liver coupled with increased amounts of fatty acids could help explain, in part, the fatty liver resulting from alcohol administration. The purpose of the following study was to determine if such an effect does occur. PMID- 1599632 TI - Effect of moderate ethanol consumption on mammary gland structural development and DNA synthesis in the female rat. AB - Epidemiological and experimental evidence provides support for a positive association between alcohol consumption and the development of breast cancer. To examine a mechanism for this association, young female Sprague-Dawley rats were pair-fed liquid diets containing ethanol at 0%, 15%, 20%, and 25% of calories for 32 days. The structural development and DNA-labeling index of the mammary gland were determined. Ethanol consumption at 20% and 25% of calories increased the density of carcinogen-sensitive terminal end bud (TEB) structures and decreased the density of carcinogen-insensitive alveolar bud structures of the developing mammary gland as compared to ad lib-fed and pair-fed controls. Consumption of ethanol at 20% and 25% of calories was also associated with a significant enhancement in the DNA-labeling index of mammary gland TEB structures, the target tissue for chemically-induced rat mammary tumorigenesis. In a separate study, serum progesterone but not estradiol, was decreased for rats fed ethanol at 25% of calories as compared to ad lib-fed and pair-fed controls. Thus moderate ethanol consumption at 20% and 25% of calories can delay the maturation and increase TEB DNA synthesis of the normal rat mammary gland. These changes may be explained by an ethanol-associated decrease in serum progesterone, a hormone important for the maturation of the mammary gland epithelium in the young female rat. PMID- 1599633 TI - A comprehensive review of the salt and blood pressure relationship. AB - Salt has played an important role in the human diet since earliest times. However, increases in the availability and consumption of dietary salt have raised concerns that excessive intakes may cause hypertension. Although recent research has linked salt intake to variations in blood pressure, definitive conclusions have been lacking. Uncertainties in this area are due to the complex effects of salt on the cardiovascular system and on blood pressure regulation. Nevertheless, many of these complexities are now well understood and have been summarized in this review. Among the topics we examine are the effects of salt on fluid and electrolyte homoeostasis; potential mechanisms of salt-induced hypertension; the epidemiology of salt intake and blood pressure; the effects of salt restriction and supplementation on blood pressure regulation; the potential roles of sodium and chloride ions, as well as interactions with dietary potassium, calcium, and magnesium; current theories of salt sensitivity; the clinical risks of dietary salt depletion; and the dietary sources of salt. PMID- 1599634 TI - Recommendations for routine blood pressure measurement by indirect cuff sphygmomanometry. American Society of Hypertension. PMID- 1599635 TI - Effect of calcium supplementation in an older population with mildly increased blood pressure. AB - This study was undertaken to determine if calcium carbonate supplementation could reduce blood pressure in an older population that had mildly increased pressure and if blood pressure reduction could be maintained over the course of 1 year with continued supplementation. Volunteers 50 to 80 years of age were included if their systolic blood pressure (when not taking antihypertensive medication) was consistently greater than or equal to 140 mm Hg or if diastolic blood pressure was greater than or equal to 90 mm Hg during a 4-week baseline period. Each subject then received placebo tablets for 4 weeks followed by 1 g calcium carbonate tablets for 12 weeks in a single-blinded fashion. If either systolic or diastolic blood pressure was reduced by at least 5 mm Hg with calcium supplementation as compared to placebo, calcium supplementation was continued for 36 weeks. A 25% subsample of subjects completed a 12-week placebo run-out. Supine and standing systolic and diastolic blood pressure did not change significantly with 12 weeks of calcium carbonate as compared to placebo (P = NS). In 42 of 103 subjects with at least a 5 mm Hg initial decrease in blood pressure who were continued on calcium supplementation, blood pressure did not change significantly through 36 weeks. In the 12 subjects who completed the placebo run-out period, systolic pressures increased significantly (P less than .05) and did not differ from baseline (P = NS). There is no evidence in this study for general use of calcium supplementation to reduce blood pressure in an older population.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599636 TI - Comparison and interaction of low dose felodipine and enalapril in the treatment of essential hypertension in elderly subjects. AB - The antihypertensive effect and tolerance of the combined low doses of felodipine and enalapril (5 + 5 mg daily) were compared with those of either drug at a higher dose level (10 mg daily). Our double-blind, three-way crossover study (balanced Latin square design) involved 36 elderly subjects (mean age 67 +/- 6 years) with essential hypertension. After a 4-week placebo run-in phase the subjects were randomized to the active treatment periods, starting with 5 mg felodipine plus 5 mg enalapril, 5 mg felodipine, or 5 mg enalapril daily for the first 4 weeks. The doses in the felodipine and enalapril periods were then doubled for another 2 weeks. All medication was given once daily in the morning, and blood pressure was measured 24 h after a previous dose. The supine blood pressure for subjects given placebo was 178/101 mm Hg. After 6 weeks' treatment systolic and diastolic supine blood pressures were significantly lower with 5 mg felodipine plus 5 mg enalapril (154/85 mg Hg) than with 10 mg felodipine (159/88 mm Hg) or with 10 mg enalapril (162/91 mm Hg), and the diastolic blood pressure was significantly lower with felodipine than with enalapril. At the end of the felodipine plus enalapril, felodipine, and enalapril treatment periods, 75, 69, and 56% of the subjects, respectively, had a supine diastolic blood pressure 90 mm Hg or less. The combination was tolerated better than either monotherapy. The most commonly reported adverse event was swollen ankles, which occurred in one, nine, and five subjects during felodipine plus enalapril, felodipine, and enalapril treatment, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599637 TI - Blood pressure responses to sucrose ingestion in four rat strains. AB - Among four strains examined, spontaneously hypertensive rats (SHR) show a marked (20 mm Hg, P less than .01) systolic blood pressure elevation (SBP), Sprague Dawley (SD) and Wistar-Kyoto (WKY) rats developed a moderate elevation (8 mm Hg, P less than .01), and a normotensive Wistar rat (WAM) had a lesser SBP elevation (6 mm Hg, P = NS) after excess sucrose ingestion. The SBP elevations found in SHR were noted at 2 and 4 weeks after starting the dietary treatments. Corresponding with SBP changes, plasma renin activity (PRA), aldosterone, and neuropeptide Y (NPY) concentrations all decreased with the high sucrose-low protein diet compared to the low sucrose-high protein diet, while circulating insulin levels were unchanged. Although norepinephrine (NE) and epinephrine (E) excretion tended to be higher in the rats eating the high sucrose-low protein food, the differences were not statistically significant. The differences in these parameters could influence the SBP in SHR, SD, and WKY, but virtually similar qualitative and quantitative blood and urinary findings were found in WAM, a strain of rat that showed no significantly increased SBP. Removing one kidney increases the CHO-induced SBP response of WKY to levels comparable to those seen in SHR, converting a moderate responder to a highly sensitive one. We conclude that under well-controlled conditions there are obvious differences in the SBP response to the macronutrients in the diets of various rat strains and that SHR possess some intrinsic mechanism(s), most likely associated with renal metabolism, which make this strain more sensitive to refine CHO-induced SBP elevations. PMID- 1599639 TI - Pediatric transplantation. PMID- 1599638 TI - Can that which is unsavory be eaten without salt? PMID- 1599640 TI - Skin transplantation. AB - Transplantation of skin has been recognized as a method to increase the survival of patients who have suffered a massive skin deficit. Until about 30 years ago, a patient who suffered a 60% BSA skin deficit usually died from the effects of overwhelming sepsis. Great strides have since been made in the techniques and technology of skin transplantation. Many different methods are now used to enhance wound closure and to maximize the functioning and cosmesis of the grafted areas. Current methods of permanent wound closure include autografting, Integra with epidermal autografting, cultured epithelial cells, and microskin grafting. Other methods of temporary wound closure include allografts, xenografts, and synthetic materials. These temporary wound coverings act as a "second skin" and keep the wound free from infection while preventing the loss of fluid from the granulation bed. Research continues to strive toward faster wound closure with minimal functional and cosmetic deficits. PMID- 1599641 TI - Immunology and organ transplantation in the neonate and young infant. AB - Cardiac replacement in neonates and infants with incurable complex heart defects has been performed successfully at the Loma Linda University Medical Center since 1985. Studies of over 125 infant transplants have revealed unique characteristics of the newborn response to foreign tissue. As compared to that of older infants, the neonatal immune system is remarkedly receptive, a phenomenon highlighting the impact of maternal-fetal incompatibility on subsequent neonatal immune development. PMID- 1599642 TI - New directions in pediatric heart transplantation. AB - New developments in pediatric heart transplantation have influenced the nursing management of these patients. The patient population has changed over the past few years with an increase in patients with congenital heart disease and larger numbers of infants and young children. The management of patients prior to transplantation has become more complex, with new pharmacologic agents and the use of mechanical assist devices as a bridge to heart transplantation. The importance of accurate assessment and management of pulmonary hypertension both before and after transplantation have been recognized. FK506, a new immunosuppressant in clinical trial, appears promising as both a maintenance therapy and a rescue drug with fewer side effects than cyclosporine. The trend toward outpatient and home care for many transplant-related therapies reflects the wider trend in health care. The practice of the critical care nurse involved in pediatric heart transplantation has been influenced by these recent changes. PMID- 1599643 TI - The pharmacokinetics and pharmacodynamics of immunosuppressive agents. AB - Designing immunosuppressive regimens for the pediatric transplant patient is challenging because one must balance the need to provide adequate immunosuppression without interfering with normal growth processes or causing long-term adverse consequences. To optimize immunosuppressive therapy and minimize toxicity, it is necessary for the nurse to be knowledgeable of the pharmacokinetic and pharmacodynamic characteristics of the various agents. It is also important to understand which drugs interact with immunosuppressive agents and how to manage these interactions. PMID- 1599644 TI - Pediatric lung transplantation: an emerging program. AB - Success has many measures, and team members each have personal criteria, but the success of our program is measured in the lives of our patients. To this end, every person associated with the program had a sense of ownership in it. It was imperative, in overcoming resistances, to treat people as individuals with valuable input, involve those affected in the planning, and provide complete and accurate information. Every person understood the process as a team effort. No one person acted alone, although key persons orchestrated the efforts of many. The instruments used were team building, communication, commitment, and collaboration. Problems and resultant pressures were viewed as challenges and opportunities for growth. When mistakes were made, we tried to learn from them, support each other, and move forward. Emphasis was on accomplishments, strengths, and unrealized potential. We learned from each other and from our patients. A close-knit team is an essential component of a successful program. The team is composed of professionals as active participants with mutual goals and a common purpose. Each member brings unique expertise, insights, personality, and experience in a cooperative venture to exchange information, identify problems, and reach a consensus. Time acts as a catalyst for members to learn to respect and appreciate each other. Cohesiveness evolves in a climate of acceptance, flexibility, and understanding. Members support and help each other. Consumers are involved with team members to participate in planning for care. In the space of 1 year, in spite of initial chaos from the Ready! Fire! Aim! approach, we have developed a sophisticated, comprehensive program for children with end-stage lung disease that can grow from a solid foundation. As we approach the second year and gain experience, we continue to evaluate our results and refine our aim. PMID- 1599645 TI - Liver transplantation: living-related donations. AB - The LRLT procedure appears to be a promising alternative and adjunct to conventional liver transplantation. The advantages to this technique are a donor for each recipient, an improved quality of graft, and a reduction in pretransplant mortality in children. The procedure is not without risks, but the overall benefits seem to outweigh these risks, and only future experience will tell otherwise. Will there continue to be a need for such a procedure? We believe there will be, because the number of candidates needing transplantation will continue to grow and the demand for cadaveric organs will never be met. However, the procedure is extremely labor and resource intensive, and it is our belief that only a handful of large major medical centers will be able to adopt a live donor program. PMID- 1599646 TI - Cell transplantation as replacement therapy for the future. AB - Cell transplantation and tissue engineering techniques are being developed to generate new functional tissues for human applications. New techniques have been developed to generate new cartilage for reconstructive applications and new liver tissue as replacement therapy. Devices are constructed using synthetic polymers as scaffolding attached to tissue-specific cells, thereby allowing for tissue remodeling and functional replacement. PMID- 1599647 TI - Caring for families of pediatric transplant recipients: psychosocial implications. AB - Organ transplantation is allowing the hope for survival and an improved quality of life to become a reality for many children with end-stage diseases. Most pediatric transplant recipients are active and able to participate in age appropriate activities. Despite dramatic symptomatic improvements, however, children and families continue to face major psychosocial stresses. Family stresses are related to the uncertainty of the child's future health and well being, role strain, social isolation, and financial burdens. Pediatric transplant recipients may have difficulties with psychosocial adjustment, especially related to dissatisfaction with the cosmetic side effects of immunosuppressive therapy and a lack of socialization skills or social competence. Psychosocial stresses faced by children following transplant may result in behavior problems, depression, poorer social adaptation, or noncompliance. The psychosocial adaptation of pediatric transplant recipients can be promoted through support and counseling from health professionals caring for these families. More research is needed to evaluate the psychosocial implications of pediatric organ transplantation and identify effective methods of providing psychological support and promoting adaptation in these children. PMID- 1599648 TI - Acute myocardial infarction. PMID- 1599649 TI - Coronary vasculitis. AB - Although patients with immune system dysfunction leading to MI may be a small subpopulation, they present an interesting challenge. Early recognition of their condition and prompt anti-inflammatory therapy, along with modification of cardiac rehabilitation and teaching protocols, will promote favorable long-term outcomes. PMID- 1599650 TI - Drug-induced myocardial ischemia and acute myocardial infarction. AB - Myocardial infarction generally occurs in the presence of known risk factors and identifiable coronary artery disease. Atypical presentations due to therapeutic and illicit drug use are documented, however, and lead to the consideration of alternative pathophysiologic rationales for myocardial infarction. This article discusses central nervous system stimulants and other drugs that have the potential for myocardial damage and their nursing implications. PMID- 1599651 TI - Acute myocardial infarction in women. AB - Although CHD is the leading cause of death in women, little is known about their response to and recovery from an acute MI. The medical and nursing care offered to women following an MI is based primarily on research studies of men. Few studies have included only women, and those that have compared women and men are limited by sample sizes that are too small for meaningful comparisons and study variables that reflect men's concerns (e.g., specific risk factors or return to work issues). Women's cardiovascular anatomy and physiology differ somewhat from men's. Women average smaller chests, hearts, and coronary artery vessel diameters and different body fat distributions. Their cardiovascular systems are designed to adapt to the extraordinary demands of pregnancy and childbirth and do so by modifying diastolic, rather than systolic, function. Similar physiologic changes are often seen in response to exercise. Women's higher levels of estrogen and progesterone influence lipid metabolism and hormone receptor activity. Thus, diagnostic tests that are based on research with men (e.g., ECGs and exercise stress tests), show more false-positive and false-negative results in women. Additionally, therapeutic interventions (e.g., PTCA and CABG) that were developed for men have been less effective for women. CHD is apparently expressed differently in women. Diabetes mellitus is a strong, independent risk factor for CHD in women and results in a risk similar to that of nondiabetic men. More women present with angina as an initial manifestation of CHD than with MI and rarely have sudden cardiac death. Women experience more complications than men and a higher mortality following acute MI. They derive less benefit from medical or surgical therapy and experience more side effects. Many aspects of women's response to acute MI reflect gender rather than biologic differences. Women's worlds, the sociocultural contexts within which they live, and their activities are qualitatively different from men's. The nursing care offered to women should be based on sound scientific rationale that responds to these unique experiences and concerns. PMID- 1599652 TI - Geriatric acute myocardial infarction: a challenge to recognition, prompt diagnosis, and appropriate care. AB - The presentation of an AMI in the older person is often atypical, with a lower incidence of classic chest discomfort but increasing incidence of dyspnea, syncope, stroke, and acute confusion. Atypical presentation is especially common in those 85 years and older. The altered pattern of symptoms predisposes the elderly to a delayed or missed diagnosis. Delay in diagnosis may also occur when the ECG is nondiagnostic. In addition, enzyme elevations may be lower and fail to reflect the extent of myocardial damage. Thus, among the greatest challenges confronting critical care nurses is that of caring for elderly patients presenting with atypical AMI and concomitant polypathology. Nurses who are well informed about the normal age-related changes in the cardiovascular system contribute to more accurate and timely diagnosis and treatment of AMI in the elderly. PMID- 1599653 TI - Electrocardiographic considerations in right ventricular infarction. AB - Right ventricular infarction frequently occurs in the setting of infarction of the inferior wall of the left ventricle. Although there are several protective mechanisms that may limit the size of the infarction, right ventricular damage can result in right ventricular failure and cardiogenic shock. ECG manifestations of right ventricular infarction can facilitate the early recognition of this syndrome. The standard 12-lead ECG may provide some evidence of infarction of the right ventricle. ST-segment elevation in right precordial leads, however, is far more reliable in establishing a diagnosis. These leads should be recorded immediately if the standard 12-lead ECG reveals an acute inferior wall MI. Continuous ST-segment monitoring may be useful in the early detection of ongoing right ventricular ischemia. ECG markers can aid in the prompt institution of appropriate treatment. It is clear that early recognition of right ventricular infarction can have important diagnostic and therapeutic implications. PMID- 1599654 TI - Clinical significance of ST-segment monitoring. AB - Establishing monitoring guidelines is important for identification of electrophysiologic changes in critically ill patients. Inclusion of continuous ST monitoring can alert critical care nursing staff to ischemia, electrolyte changes, and activity intolerance, as well as provide an objective measurement of the efficacy of nursing interventions. This simple technology, a software addition to the current bedside hardware, can assist in salvaging myocardium, decreasing anxiety by reducing pain episodes and their duration, and identifying early electrophysiologically significant drug and electrolyte changes. Nursing research is essential in establishing additional indications for continuous ST monitoring and in evaluating the usefulness of the continuous 12-lead ST-segment monitoring systems as they come into use. PMID- 1599655 TI - Ventricular remodeling following myocardial infarction: a description of the pathologic process, current investigation, and suggested therapy. AB - The pathophysiologic process of ventricular remodeling after AMI involves an alteration in myocardial cell contraction. The stretching and redistribution of myocardial cells in the ischemic area promote dyssynergic contraction and an overall reduction in ventricular function. Expansion of the infarcted area and volume-overload hypertrophy of the uninfarcted area remodel the shape of the ventricle. Ventricular enlargement and dilation are associated with early mortality and morbidity. This has prompted further study to identify measures that can attenuate the process. Limited investigation on human subjects suggests that ACE inhibition reduces ventricular wall stress and preserves ventricular shape and function. A multicenter trial, SAVE, is under way to study the effects of long-term captopril therapy for patients suffering from AMI. This study and future investigations will focus on inhibition of ventricular remodeling following AMI in the hope of reducing symptomatic CHF and mortality. PMID- 1599656 TI - Myocardial reperfusion injury: the critical challenge. AB - Oxygen-free radical production and reperfusion injury are complex mechanisms. New and improved methods for maximizing the benefits of reperfusion while minimizing reperfusion injury are on the horizon in the 1990s. Critical care nurses play a crucial role in the assessment, planning, and intervention of patients experiencing the deleterious effects of free radicals and reperfusion injury. Thus, a sound knowledge base in the pathophysiology of reperfusion injury, the detrimental effects of free radicals, and the potential benefits of free-radical scavengers is essential. PMID- 1599657 TI - Percutaneous cardiopulmonary bypass support: a new approach to high-risk angioplasty. AB - Percutaneous cardiopulmonary bypass is a new technique for supporting systemic blood flow during high-risk coronary angioplasty procedures. This mechanical alternative, unlike traditional methods, is not limited by dependency on adequate left ventricular stroke volume. Percutaneous cardiopulmonary bypass support offers new and demanding challenges in the care of this high-risk group of patients. PMID- 1599658 TI - Mechanical interventions after acute myocardial infarction: impact on patient outcome. AB - As patients' health care needs become more complex, technologic modalities will be designed to reverse pathology and/or support physiologic function until recovery occurs or death ensues. The value of these technologies needs to be evaluated not just on their economic feasibility but on their contribution in achieving a specific patient outcome(s). Justification of the purchase and use of new technologies will be based on that articulation of economics to the achievement of a specific patient outcome(s). Mechanical devices can positively impact patient outcome, but continued research, both quantitative and qualitative, must be conducted to articulate further the relationship between the hypothesized application and specific, measurable patient outcomes. PMID- 1599659 TI - Acute congestive heart failure: pharmacologic intervention. AB - Acute CHF is a highly unstable condition that requires immediate pharmacologic intervention. Mechanisms that are normally used to control the release of neurohormones are impaired in CHF. Therapeutic interventions produce hemodynamic and clinical benefits in part by restoring a balance of the neurohormonal system. This balance is achieved by interfering with actions of vasoconstriction and potentiating the effects of vasodilation and contractility. To maintain an optimal healing atmosphere, the patient's individualized needs for social support and spiritual beliefs must be considered. How the patient perceives his or her illness may also impact patient hemodynamics and outcomes. PMID- 1599660 TI - Why phaco? PMID- 1599661 TI - The clinical features and associations of retinal emboli. AB - A series of 207 patients with retinal emboli is presented with the ocular findings and systemic associations examined. Emboli were most frequently single, unilateral, crystalline and involved the left eye. Emboli were most frequently observed at the major retinal vascular temporal arcades and posterior pole arterioles, with 40% seen at a bifurcation and 10% at an arteriovenous crossing. Non-crystalline emboli were more likely to be associated with retinal pathology, such as retinal artery or vein occlusion. Carotid ultrasound was performed in 74 patients: 18% of asymptomatic subjects had internal or common carotid stenosis greater than 75%; 21% of symptomatic patients had stenosis greater than 75%. In 70%, the stenosis was worse on the side of the embolus. In symptomatic patients, significant stenosis is more likely to be unilateral. PMID- 1599662 TI - Five-year follow-up of clear cornea trabeculectomy. AB - A five-year follow-up of a prospective trial of 21 eyes with clear cornea trabeculectomy is reported. The procedure had a 56% success rate at five years. PMID- 1599663 TI - Creeping angle-closure glaucoma. The influence of iridotomy and iridectomy. AB - In 16 patients (30 eyes) with creeping angle-closure glaucoma YAG laser iridotomy or surgical iridectomy was performed as part of treatment. The initial characteristics of the affected eyes (refractive state, intraocular pressure, anterior chamber depth, iris contour, gonioscopic features, extent and severity of synechia formation and result of dark-room testing in six eyes) are recorded, and also the influence on these features of iridotomy or iridectomy. Intraocular pressure was reduced on average by 2.46 mmHg (1.72 mmHg in non-trabeculectomised eyes) (P less than 0.02), and anterior chambers deepened on average by 0.05 mm (P less than 0.05). Extension of peripheral anterior synechiae was recorded in nine eyes. PMID- 1599664 TI - Increased numbers of higher left intraocular pressures in 428 patients referred to the glaucoma clinic. AB - Seventy-four per cent of 428 patients referred to the glaucoma clinic at Concord Hospital exhibited intraocular pressure (IOP) asymmetry. There was a preponderance of left eyes, in that two-thirds of the patients with asymmetrical pressures had the higher IOP in the left eye. As the degree of asymmetry increased, this trend became more pronounced. In addition, the statistically significant difference between right and left mean IOP among the glaucoma patients was not found among normal controls, even when the order of testing the eyes was reversed. PMID- 1599665 TI - Ophthalmic manifestations of head injury. AB - Head injuries are frequently associated with ophthalmic problems. The commonest problems seen in this series of 161 patients with head injury were problems with poor accommodation (16% of patients; 58% of these persisted), convergence (14% of patients; 35% of these persisted), pseudomyopia (19%; 55% persisted) and optic atrophy (26% of the patients; 78% of these were mild and easily missed on routine testing, and 22% were severe). Motility disorders were common, especially cranial nerve palsies. Other less frequent motility disturbances included apparent inferior oblique palsy, comitant esotropia, and exotropia which was often of the convergence insufficiency type. PMID- 1599666 TI - Modern management of sixth nerve palsy. AB - Between November 1982 and September 1991, 179 patients with unilateral or bilateral sixth nerve palsy were treated in the Botulinum Toxin Strabismus Clinic at Moorfields Eye Hospital. Indications for treatment included prophylaxis (as part of a prospective treatment trial), maintenance therapy, diagnosis and adjunct to surgical therapy. A management plan for established sixth nerve palsy based on the rational use of toxin and surgery is suggested. PMID- 1599667 TI - A quantitative scale for the Barrett keratoscope. AB - By allowing the surgeon to measure and modify corneal curvature during wound closure, intraoperative keratometry can reduce postoperative astigmatic errors. A number of keratometric devices have been developed over the last 10 years, each offering a compromise between cost, accuracy and ease of use. The Barrett keratoscope is a simple, inexpensive hand-held device which gives a qualitative indication of the degree of astigmatism. Addition of a transparent overlay, as described in this paper, sets the distance at which the keratoscope is held and allows the magnitude of the astigmatism to be determined, thereby enabling refined adjustment of the suture tension during wound closure. We describe the error in estimation of astigmatism due to the effect of the distance at which the keratoscope is held from the cornea. PMID- 1599668 TI - Micrographically controlled excision (Mohs' surgery) of basal cell carcinoma around the eye. Combined dermatological surgical clearance and oculoplastic surgical repair. AB - Periorbital infiltrative basal cell carcinomas are notoriously difficult to treat, particularly those around the medial canthus. Micrographically controlled excision with horizontal frozen sections (Mohs' surgery) allows for clearance of the tumour with minimal loss of normal tissue. Once the tumour has been completely removed, the defect can be repaired by the oculoplastic surgeon for the best functional and cosmetic result. This is the ideal treatment for tumours with a contiguous growth pattern that are liable to be seriously over or under treated by other modalities. The technique requires special training for both the operator and the Medical Laboratory Scientific Officer (MLSO). It is costly in time and manpower but in selected cases, where recurrent tumour is most dangerous and where tissue conservation is paramount, it may be invaluable. Close collaboration between dermatological and oculoplastic surgeons in such cases probably offers the patient the best treatment and outcome. PMID- 1599669 TI - Eyelid and fornix reconstruction in bilateral abortive cryptophthalmos (Fraser syndrome). AB - Cryptophthalmos refers to a group of uncommon congenital anomalies of eyelid formation that can occur alone or in combination with multiple congenital anomalies as part of the Fraser syndrome. We present a case of bilateral abortive cryptophthalmos in a child with Fraser syndrome and discuss the problems of surgical management. A brief discussion of isolated and syndromic cryptophthalmos, including normal eyelid development, the pathogenesis of cryptophthalmos, and the management options follows. PMID- 1599670 TI - Partly reversible visual failure with methanol toxicity. AB - Methanol is a highly toxic substance which is used as an industrial solvent and in automotive antifreeze. If accidentally ingested blindness or death may result. The case of a young woman who developed sudden onset of visual failure following ingestion of a methanol-fortified beverage is presented. Although she failed to seek immediate medical help visual function improved. Acute changes of bilateral optic disc hyperaemia and venous engorgement were present at initial examination. She subsequently developed optic disc atrophy together with glaucomatous-like cupping of the optic discs. The aetiology of visual failure in methanol poisoning is discussed, as are the current therapeutic guidelines in the management of acute cases. PMID- 1599671 TI - Spontaneous visual improvement in the presence of posterior capsule opacification. AB - We report a case of a patient who had reduced visual acuity due to posterior capsular opacification after extracapsular cataract extraction and posterior chamber lens implantation. Capsulotomy was not performed. Over the subsequent two years visual acuity returned spontaneously to normal. PMID- 1599672 TI - Cosmetic corneal tattooing. PMID- 1599673 TI - Juvenile blow-out fractures. PMID- 1599674 TI - Rehabilitation after removal of the inferior oblique muscle. PMID- 1599675 TI - Fred Hollows' autobiography. PMID- 1599676 TI - Another method for quantitative trabeculectomy. PMID- 1599677 TI - First Australian excimer laser keratectomy patients. PMID- 1599678 TI - Enhanced in vitro growth of murine fibroblast cells and preimplantation embryos cultured in medium supplemented with an amphipathic peptide. AB - Preliminary studies on the proliferative effects of lytic peptides were carried out using NIH 3T3 murine fibroblast cells and human lymphocytes. Cells were cultured in various concentrations of three different amphipathic peptides (SB 37, Shiva-1, and Vishnu), and enhanced proliferation was determined by uptake of 3H-thymidine with treated cells compared with control cultures. Enhanced proliferation of 3T3 cells was observed in cultures containing 50 microM or less SB-37. The primary study consisted of 263 four-cell- to eight-cell-stage mouse embryos from naturally bred mice and incubated in Whitten's medium containing 0.2, 1, or 10 microM of the amino terminus of an amphipathic cecropin B analog (Vishnu) or in Whitten's medium alone. Embryos were cultured to the hatched blastocyst stage, and effect of treatment was determined by the rate of growth to that stage of development. Statistical analysis revealed that culture in all three levels of Vishnu significantly accelerated in vitro growth of these stages of preimplantation embryos compared with controls. These results indicate that Vishnu promotes increased cleavage rates of embryos in vitro. A growth factor receptor clustering mechanism of action is proposed. This peptide may have some potential as an embryo culture medium additive to enhance in vitro growth rate. PMID- 1599679 TI - Cyanide-resistant reduction of nitroblue tetrazolium and hydrogen peroxide production by the rabbit blastocyst. AB - The ability of the rabbit blastocyst to reduce nitroblue tetrazolium (NBT) to formazan in the presence of cyanide was assayed as an indicator of extramitochondrial oxidase activity capable of generating the superoxide radical. A cytochemical method initially developed for the detection and localization of hydrogen peroxide production at the ultrastructural level in phagocytosing leukocytes (Briggs et al.: J Cell Biol 67:566, 1975) was also applied to the blastocyst. The results demonstrate that the rabbit blastocyst acquires the ability to reduce NBT by a cyanide-insensitive process and to generate hydrogen peroxide between the fourth and fifth days postcoitum. The enzymatic activity responsible is apparently an NAD(P)H-dependent oxidase in the outer, microvillous plasma membrane of the trophoblast. PMID- 1599680 TI - Importance of mammalian sperm metalloendoprotease activity during the acrosome reaction to subsequent sperm-egg fusion: inhibitor studies with human sperm and zona-free hamster eggs. AB - We have previously shown that each of the metalloendoprotease (MEP) inhibitors phosphoramidon, diethylenetriaminepentaacetic acid, and carbobenzoxy-L phenylalanine, when present only during the human sperm acrosome reaction (AR), will not inhibit the AR or sperm motility but will decrease the number of sperm that penetrate zona-free hamster eggs. The present study was designed to investigate whether this inhibition of penetration is due to an effect on sperm binding to the egg plasma membrane and/or to an effect on the actual membrane fusion event. In these studies we used ionomycin to initiate the AR and assayed binding in a Ca(2+)-free medium and fusion in Ca(2+)-containing medium in the same experiment. Eggs were loaded with the fluorescent dye Hoechst 33342, and the appearance of fluorescence in a sperm head indicated that fusion had occurred. The three MEP inhibitors reduced binding only slightly but inhibited the actual fusion step by 50-60% (determined with an equation that corrected for any inhibition of fusion due to inhibition of binding). MEP inhibitors present only during gamete interactions had little or no effect on fusion. We also found that phosphoramidon-inhibitable MEP activity was released during the ionomycin initiated AR. Incubation of AR supernatant containing MEP activity with previously acrosome-reacted, phosphoramidon-treated sperm resulted in a large reversal of the phosphoramidon-inhibitory effect on sperm-egg fusion. These results support the hypothesis that the acrosomal phosphoramidon-inhibitable MEP released during the AR acts directly or indirectly during that event to increase the fusibility of the sperm plasma membrane region required for subsequent sperm egg fusion. PMID- 1599681 TI - Cortical granule complements in human oocytes undergoing partial zona dissection. AB - This study was performed to evaluate the effects of mechanical stimulation and sucrose treatment on the oocyte activation process. Fresh and aged human oocytes were exposed to sucrose and zonae were dissected with microneedles before fixation and quantitative analysis of cortical granules by transmission electron microscopy. Examination of the mean number of cortical granules/analyzed segment revealed no significant differences between control oocytes or oocytes treated with sucrose or sucrose treatment followed by zona dissection. A significant decline in the number of cortical granules/segment was observed for oocytes undergoing prolonged culture after dissection (P less than 0.05). Thus, zona dissection and sucrose exposure of freshly aspirated mature human oocytes do not result in classical oocyte activation. PMID- 1599682 TI - Perivitelline space of mammalian oocytes: extracellular matrix of unfertilized oocytes and formation of a cortical granule envelope following fertilization. AB - Extracellular matrices (ECM) present around unfertilized and fertilized mammalian oocytes were studied ultrastructurally in samples prepared in the presence of ruthenium red to facilitate stabilization of extracellular materials. Unfertilized mouse, hamster, and human oocytes have an ECM comprising granules and filaments in their perivitelline spaces (PVS). This matrix is more abundant in the human than in hamsters and mice. The granule/filament matrix appears identical to the matrix seen between cumulus and corona radiata cells following ruthenium red processing and previously shown to comprise protein and hyaluronic acid. By including ruthenium red during fixation, it is possible to demonstrate the existence of cortical granule exudate in the PVS of fertilized oocytes from hamsters, mice, and humans. Much of the cortical granule exudate is trapped in the PVS and forms a new coat around the fertilized oocyte. This material is particulate when stained with ruthenium red and appears to be uniformly dispersed around the entire oocyte surface. We refer to this new coat as the cortical granule envelope. This envelope is observed in the PVS of all developmental stages up to and including blastocysts in all three species. Following hatching of mouse and hamster blastocysts, the cortical granule envelope is no longer present. Possible functions of this envelope are discussed. PMID- 1599683 TI - Thyroid stimulating hormone enhancement of bovine oocyte maturation in vitro. AB - Efforts to improve bovine embryonic development in vitro involved study of effects of thyroid stimulating hormone (TSH) alone or in combination with LH on bovine oocyte maturation (IVM). Putative effects were assessed by observing cumulus expansion (CE), fertilization (IVF), and development to morulae/blastocysts (M/B). Effects of prolactin (PRL) were also investigated. Variables for the 24-hr IVM interval were no hormone (control), TSH (0.1, 0.5, or 1.0 micrograms/ml) or PRL (10, 100, or 1000 micrograms/ml), luteinizing hormone (LH) (0, 10, or 100 micrograms/ml) + TSH (0.1 or 0.5 micrograms/ml), and serum (20%, v/v) + 0.5 micrograms TSH/ml; data were from 4-5 trials for each IVM treatment. Higher proportions of oocytes exhibited complete CE with hormones or serum than without (P less than 0.05). All oocytes (with and without CE) were inseminated with heparin-capacitated sperm. A higher proportion of inseminated oocytes cleaved after IVM with 0.5 micrograms TSH/ml (53.4%) than for other TSH treatments (P less than 0.05). The combination of TSH (0.1 and 0.5 micrograms/ml) with 10 micrograms LH/ml for IVM enabled higher proportions (P less than 0.05) of ova to fertilize (67.4 and 69.2%) than did medium alone (28.3%), LH (10 micrograms/ml) alone (54.1%) or serum + 0.5 micrograms TSH/ml (55.6%). No improvement in proportions undergoing fertilization was seen after addition of TSH to 100 micrograms LH/ml for IVM. Frequency of CE and cleavage did not differ among PRL treatments. More M/B developed from cleaved ova after IVM with LH or TSH than with PRL or no hormone (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599684 TI - Electrofusion-induced intracellular Ca2+ flux and its effect on murine oocyte activation. AB - These experiments were designed to monitor influx of extracellular Ca2+ into the murine ooplasm following a 1.56 kV.cm-1 direct current (DC) electrofusion pulse and subsequently to determine its effect on rate of activation. Pulse media consisted of non-electrolyte (0.3 M mannitol) and electrolyte (phosphate-buffered saline; PBS) media each containing 0.0, 0.05, or 0.9 mM Ca2+ (groups T1-T3 and T4 T6, respectively). Cumulus-free oocytes were incubated in 100 microliters drops of PBS containing 2 microM of the calcium indicator fluo-3/AM for 60 min at 37 degrees C. Fluo-3/AM-loaded oocytes were equilibrated for 7 min in assigned treatment media (T1-T6) prior to application of DC pulse. Change in fluorescent intensity was monitored for 6.5 min after DC pulse by photon counting spectrofluorometry. Fluorometric measurements demonstrate a dramatic rise in intracellular free Ca2+ (Ca2+i) following DC pulse is associated with Ca2+ ion concentration in the pulse medium. Significantly (P less than 0.01) higher Ca2+i levels were observed when 0.9 mM Ca2+ was added to the pulse medium (T3 and T6) compared with pulse medium containing lower Ca2+ ion concentrations (T1, T2, T4, and T5; P greater than 0.05). Differences (P less than 0.01) were observed in peak Ca2+i levels 18 sec after pulse with mean percent change in fluorescence of 5.1%a, 33.9%b, 112.7%c, 1.2%a, 9.3%a, and 99.9%c for T1-T6, respectively (values with different superscripts are significantly different at P less than 0.01). Increased oocyte membrane permeability to Ca2+ ion after DC pulse was observed for a minimum of 5 min after delivery of the 1.56 kV.cm-1 pulse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599685 TI - G1 events and the regulation of genes for S-phase enzymes. AB - The genes for S-phase enzymes are expressed at low levels in quiescent mammalian cells but at high levels during DNA replication. Regulation occurs at multiple levels by mechanisms that are different for each gene. Current research is focused on identifying the control elements and trans-acting factors for each gene and establishing relationships between these regulatory mechanisms and the G1 signal transduction pathway. PMID- 1599686 TI - Tumor suppressor genes in the cell cycle. AB - In the past year, two tumor suppressor genes, retinoblastoma and p53, have been established as important players in cell-cycle control, mediated by phosphorylation and by stage-specific transcription complexes. Evidence that they also participate in other transcription complexes is accumulating and searches are underway for the downstream genes under their regulation. Genes down regulated in tumor cells are being screened by subtractive hybridization to bridge the gap between transcription factors and their targets. PMID- 1599687 TI - Regulation of histone gene expression. AB - Histone genes are expressed during the S phase of the cell cycle. Control is at multiple levels and is mediated by the integration of regulatory signals in response to cell-cycle progression and the onset of differentiation. Much work has been carried out on the H4 gene promoter, which appears to be organized into a series of distinct regulatory elements. The three-dimensional organization of the promoter and, in particular, its spatial relationship with the nuclear matrix scaffold, may be important factors of transcription regulation. PMID- 1599688 TI - Cell cycle regulation in bacteria. AB - Significant progress has been made in the study of ftsZ expression and the topology of FtsZ protein localization in Escherichia coli cells. Exciting results on the identification of new genes required for chromosome resolution and partitioning after the completion of DNA synthesis have also been reported. A recent area of study is asymmetric cell division and its role in differentiation in Bacillus subtilis and Caulobacter crescentus. Biochemical activities of bacterial cell division gene products are also beginning to be addressed. PMID- 1599689 TI - The role of cytosolic Ca2+ in cell injury, necrosis and apoptosis. AB - Increases in cytosolic Ca2+ are believed to be a pivotal signal in the regulation of cell injury, cell death, cell proliferation, cellular differentiation and cellular aging. Changes in the concentration of cytosolic Ca2+ are involved in both acute and chronic cell injury, as well as in accidental or programmed cell death. Signalling in all of these phenomena is dependent on mediated activities of a number of intracellular factors, including phospholipases, proteases and endonucleases. The coordinate regulation of these factors, as well as of oncogene activation, seems to play a role both in the processes of cell injury and cell death, and in the recovery from injury in sublethally injured cells. PMID- 1599690 TI - Substrate diversity of the cAMP-dependent protein kinase: regulation based upon multiple binding interactions. AB - The proposition is forwarded that the cAMP-dependent protein kinase is one of quite a small class of enzymes wherein differential modes of binding of its multiple substrates make an important contribution to the end physiological response. It is postulated that a variety of different substrate affinities may have evolved in order to regulate the order of substrate phosphorylation. The recent elucidation of the protein's three-dimensional structure provides the opening to test this as a new concept of cellular regulation. PMID- 1599691 TI - Mammalian stress response: induction of the glucose-regulated protein family. AB - The glucose-regulated protein family consists of a set of stress-inducible proteins localized in the endoplasmic reticulum. Since their discovery in 1977, significant advances in our understanding of their structure, function and regulation have been made. Recent findings concerning the physiological roles played by the glucose-regulated proteins, and their regulations at the transcriptional, post-transcriptional, translational and post-translational levels are summarized. PMID- 1599693 TI - Cell regulation. PMID- 1599692 TI - Cell multiplication. PMID- 1599694 TI - [Revista Portuguesa de Cardiologia. Quality and prestige for the use of cardiovascular medicine]. PMID- 1599695 TI - [Treatment of arterial hypertension in the elderly]. AB - The AA. try to evaluate the therapy of arterial hypertension in the elderly. With the present day data, they think it is advisable to make it but with some limitation--the J curve on diastolic arterial blood pressure (85 mmHg) and situations that may lead to modifications of therapy, such as troubles of rhythm, gout, diabetes mellitus, hyperlipidemia and perfusion deficiencies of lower limbs. OPAL concept (Old People With Active Life styles) recommends an individualized establishment of therapy instead of standard techniques to try the minimal trouble to a good quality of life for the patient. PMID- 1599696 TI - [Echocardiographic quantification of mitral regurgitation. Comparative study with transthoracic and transesophageal Doppler color echocardiography]. AB - The quantification of mitral regurgitation by means of colour coded Doppler echocardiography still is a controversial issue. A prospective study on 86 consecutive patients with mitral regurgitation diagnosis was carried out by means of conventional transthoracic colour coded Doppler echocardiography in order to make a comparative study with results obtained by means of transoesophageal colour coded Doppler echocardiography. A systematic measurement of the following parameters was carried out in each patient: Colour coded area or mitral regurgitation jet, auricular depth of mitral regurgitation jet, severity degree of mitral regurgitation, left auricular area, mitral regurgitation ratio and transthoracic crossection plan of largest regurgitation area. Both echocardiographic techniques had the first three parameters in common. The mitral regurgitation area by transthoracic echocardiography was 370 +/- 41 mm2 and by transoesophagial technique 558 +/- 43 mm2 (p less than or equal to 0.001 - r = 0.71). The depth of mitral regurgitation by transthoracic path was 31 +/- 2.7 mm and by transoesophageal path 37 +/- 25 mm (p less than or equal to 0.01 - r = 0.74). The existing correlation between the mitral regurgitation area obtained by both techniques improved (r = 0.84) when a four camera apical transthoracic plan was used and worsened (r = 0.45) when the longitudinal parasternal path was used. We came to the conclusion that the valorization of mitral regurgitation made by both techniques is not accurately comparable, existing undervaluation in transthoracic echocardiography. The discrepancies between the two techniques are more patent and statistically more significant when longitudinal parasternal plan is used for transthoracic quantification of severity degree of mitral regurgitation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599697 TI - [Relationship between ventricular arrhythmia and clinical and echocardiographic parameters in hypertensive patients]. AB - OBJECTIVE: Evaluation in arterial hypertension (HTA) patients, of the relationship between supraventricular and ventricular arrhythmias, stage of hypertension and echocardiographic parameters. DESIGN: Retrospective study based on the files of ambulatory electrocardiography (Holter). SETTING: Arrhythmology Outpatients Clinic from a Cardiac Department. PATIENTS: Adult patients with arterial hypertension, males and females, who underwent ambulatory electrocardiography (Holter) and echocardiography examinations. MATERIAL AND METHODS: Thirty patients, 15 males and females, 54 +/- 12 years old, were studied. Arterial hypertension was stratified in three stages according with the diastolic value. Symptoms, serum potassium, left ventricular hypertrophy (LVH) on the ECG, and echocardiographic parameters such as left ventricular dimensions, shortening fraction, septal wall and posterior wall thickness and left atrium dimensions were analysed. These parameters were correlated with the arrhythmic pattern concerning the number of premature supraventricular contractions and the number and complexity of premature ventricular contractions (PVC), evaluated by ambulatory electrocardiography (Holter). RESULTS: No relation was found between the arrhythmic pattern, stage of hypertension, symptoms and LVH on the ECG. Septal wall thickness was 14 +/- 3 mm in the group of patients with PVC greater than or equal to 10/hour and 12 +/- 3 mm in the population with PVC less than 10/hour (p less than 0.04). The shortening fraction was 27 +/- 8% in the group of repetitive PVC and 34 +/- 7% in the population without (p less than 0.003). A borderline relation was found between repetitive PVC and left atrium and left ventricular diastolic dimensions. CONCLUSIONS: In a population of arterial hypertension (HTA) who performed ambulatory electrocardiography (Holter), the prevalence of frequent or repetitive PVC was low. A positive correlation between frequent PVC and septal wall thickness and an inverse relation between repetitive PVC and LV shortening fraction, was found. These conclusions are according with the literature, relating the ectopic activity with LVH or deterioration of LV function. No relation was found between arrhythmias and stage of hypertension. PMID- 1599698 TI - [Heart surgery without previous heart catheterization, in pediatric cardiology]. AB - STUDY OBJECTIVE: To determine the influence of echocardiography in the preoperative diagnosis of heart diseases in children. DESIGN: Retrospective study. SETTING: Hospitalized children admitted in Departments of Pediatric Cardiology and Cardiothoracic Surgery. PATIENTS: Children of both sexes, aged from neonate to 14 years old, with heart disease who underwent cardiac surgery. MATERIAL AND METHODS: From January 1989 to July 1990, 220 consecutive cardiac surgeries were performed in children with heart disease. The initial diagnosis was based on data from clinical examination, electrocardiogram, thorax X-Ray and echocardiogram (M-mode, 2D, conventional and colour Doppler). Patients were separated in three groups according to their ages: newborn infants less than 28 days old; infants less than 12 months old; children more than 1 year old and less than 14 years old. Patients were separated according to the investigations used further for preoperative diagnosis: whether they had or not cardiac catheterization performed prior to surgery. RESULTS: From 220 surgical interventions performed, 124 were "open heart" surgeries (9 neonates, 28 infants and 87 children) and the remaining had "closed heart" operations (14 neonates, 37 infants and 45 children). Preoperative diagnosis was mainly dependent on echocardiography, dispensing catheterization in 90 cardiac interventions. The diagnosis was confirmed at surgery or at autopsy. There were 9 deaths, 3 of which occurred in patients not submitted to cardiac catheterization. CONCLUSIONS: Echocardiography is a reliable method for investigation and establishment of the preoperative diagnosis of heart diseases in children. Its use may further reduce the need for diagnostic catheterization in children, particularly in risk groups. PMID- 1599699 TI - [Clinical case and review of the subject. Prognosis in acute myocardial infarction]. AB - Aiming to discuss the value of the prognostic indices in the acute myocardial infarction (AMI), we present two cases of AMI, where the predictable prognosis at 48 hours of the onset of symptoms is informed by the outcome of each case. In the first one, a patient in cardiogenic shock had a good evolution because he suffered a biventricular infarction that responsed well to hydric overcharge. The other case, a Killip classe I infarction, was complicated by a late left ventricular free wall rupture. We discuss the several aspects of each case, and finally we do a critical aproach of the most common prognostic indices (Killip and Kimbal classes, Peel prognostic groups and Norris prognostic groups). PMID- 1599700 TI - [Angina pectoris--particular aspects in the elderly]. AB - The incidence of the coronary heart disease increases dramatically with age, representing in Portugal the second largest cause of death in patients older than 65 years. The cause of this high prevalence of the disease is not completely understood, but the pathogenic role of the cardiovascular risk factors has a singificative importance. It seems to be essential, even in elderly, to control these risk factors in order to limit the progression of the atherosclerotic disease. Regarding symptomatology, effort dyspneia appears to be one of the most frequent disease manifestations, differing from the typical chest pain presentation observed in the younger patients. Exercise stress testing can be used safely in the elderly and it is not just an important diagnostic tool, but it is also essential to the stratification of the patients to be more agressively treated. Concerning treatment, the search and correction of the precipitating factors are a key to success in the elderly patients. Pharmacologic therapy must be prescribed in agreement with the clinical pharmacologic principles, carefully adjusted to the elderly, in order to avoid adverse drug effects. In spite, coronary bypass surgery has some higher risk in the elderly. The results obtained are satisfactory, and the patients subset with ventricular disfunction, benefit the most. Percutaneous transluminal coronary angioplasty constitutes a very atractive therapeutic modality in the elderly. Cardiac reabilitation programe are very useful in the elderly, contributing to the desired psycosocial reintegration of these patients. PMID- 1599701 TI - [Morpho-functional characteristics of the heart in the elderly]. AB - Alterations in cardiovascular structure and function with advancing age are reviewed. The difficulty to distinguish between aged related alterations and those due to coronary disease are analysed. The results of the studies in which coronary disease are excluded are compared with those in which that situation was present. Cardiac output, systolic volume and peripheral vascular resistence are the differences. The physiological adaptations of the heart to effort are analysed. The adaptation of the heart to effort is quite different according to Coronary Disease have been excluded or not on the population. PMID- 1599702 TI - [Heart surgery in the elderly]. AB - The literature of the last five years is reviewd to evaluate the mortality and morbidity of the cardiac surgery (valve replacement and aorto-coronary by-pass, single or combined) in comparison with other patients. There is some slight increase in mortality and morbidity of these patients, depending on of non cardiac causes. Cardiac surgery can improve the quality of live and increase life expectancy of these patients, but the results are influenced by age. On the surgery of valve replacement is important to avoid the funcional deterioration, because the mortality on classe IV is very high. The results of aorto-coronary by pass on the elderly are not influenced by the coronary anatomy on these ages. The mortality is slightly increased on the majority of the published results. Urgent surgery has a very high mortality on theses ages. The perfection of the surgical techniques and a carefull post-operative care are essencial factors for a good result. PMID- 1599703 TI - [The centenary of Prof. Joao Porto]. PMID- 1599704 TI - [Myocardial infarction in a young man with normal coronaries: report of a case treated with streptokinase]. PMID- 1599705 TI - Investigation of the role of macrophages and endogenous interferon-gamma in natural resistance of mice against Legionella pneumophila infection. AB - Mice are highly resistant to Legionella pneumophila infection. To study the natural resistance, we used A/J and C57BL/6 mice which have macrophages permissive and non-permissive for the intracellular growth of L. pneumophila, respectively. The LD50 for A/J and C57BL/6 were 2.7 x 10(7) and 7.2 x 10(7) CFU, respectively, indicating that the difference in macrophage ability to regulate the bacterial growth had some effect on susceptibility to L. pneumophila. There was no difference between both strains in elimination of the bacteria from the blood stream within 5 h after infection. When mice were challenged intravenously with a sublethal dose (4 x 10(6) CFU), the bacterial burden in the liver at day 1 was significantly higher in A/J than in C57BL/6. The bacteria, thereafter, were eliminated rapidly from the liver at a similar rate in both strains. Elimination of the bacteria from the spleen and lungs was also delayed in A/J as compared to C57BL/6. Naive spleen cells of both strains in vitro could produce a large amount of interferon-gamma (IFN-gamma) one day after they were stimulated with formalin killed L. pneumophila. When anti-murine IFN-gamma monoclonal antibody was administered, the bacterial burden in liver, spleen and lungs significantly increased in A/J, and also in C57BL/6 to some extent. We suggest that the innate macrophages' ability to regulate the intracellular bacterial growth and the endogenous IFN-gamma produced in a very early phase play a critical role in murine natural resistance against L. pneumophila infection. PMID- 1599706 TI - Impaired stimulation of anti-bovine serum albumin IgG antibodies by vaccine adjuvants in murine acquired immunodeficiency syndrome. AB - The effect of three adjuvants - alum, N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), and liposomes - on the IgG antibody isotype response to bovine serum albumin (BSA), was determined in normal and LP-BM5 retrovirus infected C57BL/6 mice. Alum and MDP induced comparable levels of IgG antibodies in normal mice (predominantly IgG1 (greater than 90%)), whereas liposomes induced IgG1 (60%), IgG2a/b (30%) and IgG3 (10%) antibodies. IgG antibody levels using liposomes as adjuvant were five-fold higher than those observed with alum or MDP. Immunization after LP-BM5 infection significantly reduced the effectiveness of alum and MDP, IgG antibody levels being reduced by 80 and 90% at 3 or 7 weeks respectively. The adjuvant activity of liposomes was reduced by 55 and 65% when immunization was started 3 or 7 weeks post LP-BM5 infection. Boosting of pre-immune mice with BSA and alum, MDP or liposomes 3 weeks after LP-BM5 infection showed that, while the magnitude of the antibody response and isotype distribution was not affected, the persistence of the response was severely diminished compared to control, non infected mice. The reduced immunoadjuvant activity correlated with a reduction in the frequency of splenic Thy1.2+/CD4+ T cells. These results demonstrated that liposomes were more effective than alum or MDP in inducing IgG antibodies, and that immunoadjuvant activity for prophylactic or therapeutic immunization for all 3 adjuvants was significantly impaired by retroviral infections. PMID- 1599707 TI - Antigenic heterogeneity of strains of Saccharomyces cerevisiae and Candida albicans recognised by serum antibodies from patients with Crohn's disease. AB - The antigenic heterogeneity of twelve strains of Saccharomyces cerevisiae and serovar A and B strains of Candida albicans was investigated by cross-absorption of serum antibodies from a patient with Crohn's disease. On the basis of common antibody absorption patterns, eleven of the yeast strains were divided into Group 1 (five S. cerevisiae), Group 2 (two C. albicans, one S. cerevisiae) and Group 3 (three S. cerevisiae). The remaining three S. cerevisiae strains (Group 4) showed unique absorption patterns. The antigenic relationship between S. cerevisiae and C. albicans was further studied by cross-absorption of sera from eight patients with Crohn's disease. This confirmed a limited degree of cross-reaction between most strains of S. cerevisiae and C. albicans, but C. albicans serovar B significantly absorbed antibodies to more S. cerevisiae strains than did C. albicans serovar A. The results demonstrate considerable antigenic heterogeneity of S. cerevisiae and suggest that the elevated serum antibody levels to S. cerevisiae found in Crohn's disease are directed against multiple antigens. PMID- 1599708 TI - Polyacrylamide gel electrophoresis analysis of lipopolysaccharide from Pseudomonas aeruginosa growing planktonically and as biofilm. AB - Lipopolysaccharide (LPS, endotoxin) was extracted from biofilm and planktonically grown monoagglutinable (1118) and polyagglutinable (258 and 15703) strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients with chronic pulmonary infections. Analysis by polyacrylamide gel electrophoresis (PAGE) followed by immune-detection of LPS fractions showed an S-form appearance of strain 1118 and 258 with three distinct clusters of high molecular weight bands, whereas 15703 appeared semi-rough. LPS of semi-rough cells grown planktonically and as biofilm showed a very similar PAGE pattern; however, the core/lipid A R LPS fraction was more prominent in biofilm-LPS than in planktonic-LPS extracted from the S-form bacteria (1118 and 258). The apparent change in LPS sub-unit components of the bacteria when grown as biofilm may reflect changes in the outer membrane structure that contribute to the altered physico-chemical properties of biofilm bacteria in foreign-device associated infections and chronic P. aeruginosa lung infection in cystic fibrosis patients. PMID- 1599709 TI - The study of agglutination of trypsin-treated sheep red cells by Corynebacterium diphtheriae strains. AB - 620 Corynebacterium diphtheriae strains from 472 sick and healthy persons were studied for their adhesive activity (AA) in direct agglutination of trypsin treated sheep erythrocytes. Toxigenic strains had more active AA than non toxigenic ones which was not dependent on the presence of toxin in the culture. Neither biotype nor serotype of the strains correlated with their AA. Several lysotypes among toxigenic and non-toxigenic strains were more active than others. Toxigenic strains from patients had higher AA than those from carriers. Both toxigenic and non-toxigenic strains isolated from the prolonged carriers possessed the highest AA. It was concluded that AA measured in this way was an important colonization factor for all diphtheria strains and a pathogenicity factor for toxigenic strains. PMID- 1599710 TI - [Preliminary studies of the relationship between micronucleus formation and cell cycle. IV. Micronucleus formation induced by chemical mutagens at G0, G1, S and G2 phases of human lymphocytes]. AB - In this paper the authors studied quantitatively the micronucleus formation at various phases of interphase in human lymphocytes induced by chemical mutagens by means of control of cell culture intervals, autoradiography and block of metaphase cells etc. The results show that mutagenic anti-tumor drugs: bimolane (treatment in vitro) and thio-tepa etc. (treatment in vivo) can induce micronucleus formation at various phases of interphase in lymphocytes. The frequency of micronucleus (MNF) induced at G1 phase is significantly higher than that at G0 and G2 phase. The MNF at S phase of cells is obviously lower than at G1. This result suggests that most of the micronucleated cells at G1 phase do not enter S phase and micronucleus rarely form at S phase of cells. PMID- 1599711 TI - [Tissue-specific expression of the chimeric gene delta KpF in transgenic mice]. AB - The expression of the chimeric gene delta KpF in which the promoter region of delta-crystallin gene was replaced with the long terminal repeats (LTR) of Friend spleen focus forming virus (SFFV) was studied in transgenic mice for approaching the regulatory mechanism of the expression of chicken delta-crystallin gene. The recombinant plasmid (p delta KpF) DNA containing delta KpF gene was microinjected into male pronuclei of fertilized mouse eggs. The injected eggs were implanted into the oviducts of pseudopregnant female mice and allowed to develop to term. Subsequently, 35 mice from those eggs were born. The mice were analyzed at 2 weeks of age with respect to gene integration and expression by the method of DNA blot hybridization and immunoenzymologic assay. DNA-DNA hybridization indicated that the genomic DNA from one of the mice retained the sequences that hybridized strongly with the probe, p delta KpF. Enzyme linked immunosorbent assay (ELISA) showed that delta KpF gene was expressed in the lens, but not in the brain, muscle and liver. These results demonstrate that the essential regulatory elements for tissue-specific expression of chicken delta-crystallin gene reside in the sequences downstream from +677bp. PMID- 1599712 TI - [Construction and identification of vectors containing maize plasmid-like DNA S1 and reporter genes]. AB - The reporter Gene GUS with CaMV 35S promoter was inserted into plasmid pBS[1] in reversal direction of integration, and two kinds of recombinant plasmids were obtained. These results were verified by restriction endonuclease analysis and southern hybridization. A piece of 10.8kb fragment containing NPT II reporter gene from digested pBI121.1 by BamHI and EcoRI was ligated together with 3.9 kb fragment of plasmid-like DNA S1. Then generate a recombinant plasmid pBIS5 was generated. These three vectors can be used to transform maize protoplasts. High frequency of transformation may be expected due to homology between plasmid-like DNA S1 and maize nuclear DNA. PMID- 1599713 TI - [Genetic recombination and Fib genes transfer of the plasmid of E. herbicola CSH 1065]. AB - We inserted kanamycin resistance (Km) gene and mobilized function (Mob) gene on the plasmid of E. herbicola CSH1065 by using DNA molecular cloning and genetic recombination techniques. Therefore, the plasmid of E. herbicola CSH1065 to E. coli HB101 could be transferred by conjugation. The expression of those genes concerning fungi inhibition function (Fib) of E. herbicola CSH1065 in E. coli HB101 was observed. This result confirmed again the fungi inhibition genes of E. herbicola CSH1065 is only related to its plasmid genome not to its chromosome genome. Meanwhile those yellow pigment genes located on the plasmid don't involve the antifungi function of E. herbicola CSH1065. All those results were convinced by DNA molecular hybridizations. PMID- 1599714 TI - [Multi-origin usage for chromosome replication of suppressive integration strain of dnaA46 mutant of Escherichia coli integrated with R6K]. AB - The chromosome of temperature sensitive initiation mutant dnaA46 of Escherichia coli K-12 fails to replicate at 42 degrees C. Suppressive integration (Sin) strain integrated with the R6K plasmid was screened at 42 degrees C. Marker frequency determination of the Sin strain reveals that replication was initiated at the normal site of initiation at 30 degrees C, while at three different sites at 42 degrees C. Two of the sites have been reported in the stable DNA replication mutant, one of them is a novel site. Inhibition of chromosome replication was not observed for the recA derivative of Sin initiated at two of the initiation sites close to the normal initiation site. Inhibition was observed for chromosome replication initiated near the site where chromosome replication normally terminates. It indicates that chromosome replication initiated at sites close to the terminus is recA gene dependent. PMID- 1599715 TI - [DNA repair capacity measurement and possibility of heterozygote detection using nucleoid sedimentation technique among members taken from 3 xeroderma pigmentosum (XP) families]. AB - The nucleoid sedimentation test was used to analyse the DNA repair capacity in 35 members taken from 3 xeroderma pigmentosum (XP) families after their peripheral blood lymphocytes being exposed to UV irradiation or N-methyl-N-nitro-N nitrosoguanidine (MNNG) at a dose of 2.5 microJ/mm2 and 2 micrograms/ml respectively. The results showed that the 6 XP patients all failed to repair their damaged DNA even after 20-hour incubation at 37 degrees C. The repair ratios were 0.61 +/- 0.13 for UV and 0.44 +/- 0.15 for MNNG while those of non related normal members usually reached 0.96 +/- 0.07 and 0.71 +/- 0.07 for both UV and MNNG after 11-hour incubation. It is interesting to note that 9 obligatory heterozygotes (parents and grandparents of XP patients) and 4 highly possible heterozygotes (blood relatives of XP patients) also showed very poor DNA repair capacity: they could not accomplish their repair process even after 20-hour incubation. It has been showed that the nucleoid sedimentation test can probably be used to pick out the heterozygotes in XP families. PMID- 1599716 TI - Effect of minor illness on serum cholesterol level. AB - To ascertain the impact of minor illness on total plasma cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), we analyzed data collected on 6,880 persons examined for the Stanford Five-City Project. Overall, 8.4% of the population reported having a minor illness on the day of examination, although there were substantial variations in minor illness rates with season, city, and year of data collection. After adjustment for age, sex, body mass index, season, and city of residence, we found that those who reported minor illness at the time of examination had a lower mean TC than those who were well (195.9 mg/dL versus 201.2 mg/dL, P less than .005). HDL-C was 51.2 mg/dL in persons with minor illness, and 52.3 mg/dL in persons without (P = .13). Dietary recall data covering the 24-hour period before the examination was available on a subset of the patients. No dietary differences appeared between individuals who reported minor illness and those who did not. In a subset of 162 persons with a minor illness who were followed longitudinally for up to six years, TC adjusted for age was 191.8 mg/dL with minor illness and 196.1 mg/dL without, a difference that was not statistically significant. The results of this study imply that minor illness may contribute to some of the biological variability of TC and HDL-C. Although small, a differential rate of minor illness may sometimes significantly affect interpretation of TC epidemiological and intervention studies or the timing of measurements in clinical practice. PMID- 1599717 TI - Effect of a fact sheet reminder on performance of the periodic health examination: a randomized controlled trial. AB - Physicians' performance of the periodic health examination is often incomplete. Performance rates may be low because physicians forget recommendations for specific periodic health examination components at the time of the patient encounter. We studied the effect of providing information about seven periodic health examination actions (cervical Pap smear, mammography, fecal occult blood testing, serum cholesterol level, and influenza, pneumococcal, and diphtheria tetanus immunizations) on first-year medical residents' performance of these actions over a three-month period. We randomly selected 16 residents to receive periodic health examination recommendations, plus data supporting each recommendation, on their outpatient charts at the patient encounter. Thirteen residents who did not receive this information served as controls. Experimental and control groups achieved similar knowledge scores (0.53 versus 0.47, P = .48) and attitude scores (0.73 versus .078, P = .19) for preventive care measures on prestudy testing. The experimental group performed 10.5% of indicated periodic health examination actions, whereas the control group performed 5.8% of indicated actions (P = NS). These results suggest no clinically meaningful improvement in performance of periodic health examination actions, even when periodic health examination guidelines were available at the time of the physician-patient encounter. PMID- 1599718 TI - Does workplace health promotion decrease medical claims? AB - We examined the relationship between workplace health promotion and medical claims in 38 textile plants, considering also the effects of demographic and contextual variables (i.e., average worker age, sex ratio, racial composition, plant product, and access to medical services). Number of claims per worker varied threefold among plants but was independent of plant workforce's sex ratio, racial composition, and access to medical services. Worker age predicted claims; in a linear regression model, age, sex, race, plant product, and access explained 23% of variance in claims. Health promotion was also related to claims, and its inclusion in the model (with interaction terms involving plant product) explained 54% of variance in claims, with the deletion of race, sex, and access from the reduced model. We concluded that effective health promotion must address the contexts of different types of plant product. PMID- 1599719 TI - Coronary risk factor behavior change in hospital personnel following a screening program. AB - We conducted a worksite cardiovascular disease (CVD) awareness and education program at a large medical center. The program consisted of employee screening for blood pressure and total serum cholesterol level, dissemination of information on risk factors for CVD, counseling on behavior change, and evaluation of the screening event as an educational tool. During this five-day event, 2,284 employees were screened for hypertension and hypercholesterolemia. Consenting employees completed a health risk appraisal survey (n = 2,255) and received counseling on their results and CVD risk factors. Appropriate referrals to health care professionals and educational programs were made according to national guidelines. We developed three-month and six-month follow-up surveys and distributed them to all participating employees. The analysis of these data suggests some positive impact upon behavior change within this employee population. In addition to the two follow-up surveys, we held a second blood pressure and serum cholesterol screening eight months after the initial screening. Comparison of the levels taken from both screenings (n = 234) suggests that worksite screening programs may influence significant serum cholesterol and blood pressure reductions in high-risk employees. PMID- 1599720 TI - Quality assessment in worksite health promotion. AB - The rapid expansion of worksite health promotion programs and the proliferation of service providers have resulted in increased concern about the quality of such programs. And while employers may view health promotion programs as a service to be purchased, in general, quality standards, price, and outcomes are less well established for primary prevention programs than for other medical services. This trend creates substantial potential for inappropriate expenditures, undermining the general credibility of such programs. Recognizing the limits of epidemiologic data and the potential for misuse of health promotion activities in the workplace, the California Department of Health Services (CDHS) undertook the development of guidelines for employers' use in assessing the quality of the numerous employee health promotion or chronic disease risk reduction programs available to them. To make the use of such programs as productive as possible, the CDHS developed recommendations in two main areas: (1) general recommendations for six fundamental program planning and development activities that underlie sound health promotion programs, and (2) specific criteria for seven types of health promotion programs commonly implemented in work settings. Optimally, worksite-based health promotion programs should be part of a comprehensive effort that provides for appropriate medical oversight, referral, and follow-up procedures. These programs should be complemented by appropriate changes in the work environment and in organizational policies. Programs should also include strategies to assist employees in initiating healthier behaviors and maintaining the new behaviors once they are established. Preventive medicine and occupational medicine practitioners and medical directors should be familiar with the issues addressed by these recommendations. PMID- 1599721 TI - Quality in worksite health promotion: who is responsible? PMID- 1599722 TI - IPA payment policies for preventive services. PMID- 1599723 TI - Women's attitudes toward screening mammography. AB - Although mammography has been proven an effective tool in screening asymptomatic women, it has been underused because of poor physician and patient compliance. At a university mammography clinic in Southern California, we administered questionnaires to 381 asymptomatic women to determine what women perceived to be incentives and deterrents to mammography. A factor analysis grouped the incentives into five factors, in decreasing significance: "doctor's recommendation," "personal experience," "media," "others' recommendation," and "breast symptoms." Similarly, we grouped the deterrents according to five factors, in decreasing significance: "cost," "fear of medical intervention," "unnecessary screening," "time demands," and "transportation difficulties." We compared the relative significance of these incentive and deterrent factors for demographics, aspects of the doctor-patient relationship, and individual characteristics. Younger, married women rated incentives, particularly "personal experience," higher and deterrents lower in general than older, unmarried women who had more concerns about "cost." However, all demographic groups rated "doctor's recommendation" as the highest incentive, and we found few differences among races or socioeconomic status for any factor. Women whose physicians had initiated the discussion of mammography viewed the doctor's recommendation as a greater incentive than women who had to initiate the discussion about mammography. Women under the care of gynecologists saw the doctor's recommendation as a greater incentive than women under any other specialists' care. Gynecologists initiated the discussion of mammography and recommended screening more often than other specialists. Women with the following individual characteristics identified more incentives to mammography: knew someone with breast or other cancer, estimated themselves to be at high risk for breast cancer, or had at least one previous mammogram.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599724 TI - Breast cancer screening: effect of physician specialty, practice setting, year of medical school graduation, and sex. AB - We surveyed physicians of different specialties in a large metropolitan area to determine how their characteristics affected their performance and beliefs about breast cancer screening. Of 664 general internists, obstetrician-gynecologists, and cardiologists surveyed, we received 298 responses (45%). We found significant differences in reported performance of breast cancer screening and physicians' beliefs about mammography screening among practicing obstetrician-gynecologists, internists, and cardiopulmonary specialists. Cardiopulmonary specialists performed the fewest breast examinations and screening mammograms and were most likely to believe annual mammography screening unnecessary even for women in their 50s. We observed no difference between physicians graduating before 1960 and those graduating afterward and no differences according to physician sex. We found similar screening practices and beliefs in the three types of practice settings examined: community-based, private practices, a large health maintenance organization (HMO), and academic medical centers. Obstetrician-gynecologists and internists differed only in the frequency with which they performed breast examinations. Physicians graduating before 1960 in these two groups reported somewhat poorer performance and knowledge of breast cancer screening than those graduating more recently. A majority of all respondents disagreed with American Cancer Society guidelines for mammography screening. Physicians of all specialties reported performing far more breast examinations than screening mammograms on women of all ages, even for those 50-59 years of age. We conclude that all physicians need to improve their screening rates. However, intervention programs should first target those physicians with the greatest deficiencies in breast cancer screening performance and knowledge; these include medical specialists and older physicians in primary care specialties. PMID- 1599725 TI - Smoking rates among Rhode Island physicians: achieving a smoke-free society. AB - Over a 25-year period, regular surveys of physicians licensed in Rhode Island have recorded their smoking behavior. The six surveys show a decrease in the rate of cigarette smoking from 33% in 1963 to 4.6% in 1988. In the most recent survey, 65% of respondents reported never having smoked, and 87% of those who had ever smoked reported having quit. However, the statistic for the maximum number of cigarettes smoked regularly was higher for current smokers than for former smokers. Among physicians in the 1988 survey, most former smokers (85%) reported using only unassisted personal effort in quitting, whereas nearly half (48%) of current smokers tried methods involving assistance, such as self-help programs, group programs, or nicotine gum. Among former smokers who quit after 1983, the percentage trying assisted methods (34%) was closer to the percentage among current smokers. Apparently, remaining smokers include many heavy smokers who require more potent interventions in order to quit. Physicians in Rhode Island have almost become a smoke-free group. Their experience, coupled with their involvement in smoking prevention and cessation for their patients, can lead the rest of society on its path to becoming smoke-free. PMID- 1599726 TI - A family physician smoking cessation program: an evaluation of the role of follow up visits. AB - Our purpose in this randomized clinical trial was to compare a two-visit smoking cessation intervention by family physicians with the same intervention supplemented by additional follow-ups. Forty-one southern Ontario family physicians volunteered for the study and subsequently participated in a four-hour training program on smoking cessation techniques. Physicians advised patients who smoked and indicated an interest in attempting to quit with the help of their physician to stop smoking at the end of a regularly scheduled visit. Physicians instructed patients to make a specific appointment for an evaluation of their smoking habits. Six hundred forty-seven patients returned for that assessment and were than randomized into either the two-visit intervention group (with risk assessment, support, the setting of a cessation date, self-help literature, and a prescription for nicotine gum, where appropriate) or into the other intervention group (with the same maneuvers as well as the offer of four more supportive follow-up visits). We found no statistically significant difference in one-year, biochemically validated, sustained cessation rates between the group offered the long-term follow-up visits (12.5%) and the group given the brief intervention (10.2%). The 95% confidence interval on the difference between the groups was 2.8% in favor of the brief intervention group to 7.3% in favor of the group offered follow-up. The results do not support the value of long-term follow-up visits for smokers. PMID- 1599727 TI - No association between serum cholesterol and growth in preadolescent American children. AB - To determine the relation between serum cholesterol level (SCL) and growth in preadolescent children (2-12 years of age) in the United States, we examined the association of SCL and three measures of growth in a national sample of American children from 1971 to 1974. We investigated three parameters: sitting height, standing height, and weight and undertook separate analyses for sex and race. We found no consistent statistically significant associations with any of these three measures of growth. This result did not change when we adjusted the data for age alone or for age, poverty index, serum protein level, and hematocrit. We conclude that growth in this population group is not dependent on SCL. PMID- 1599728 TI - Understanding and using teleradiology. AB - In 1972, Webber and his coauthors closed their landmark paper with some visionary remarks that have proved to be remarkably perceptive. They hypothesized that special telephone circuits or radiofrequency channels could be used to yield "images whose grey scale and resolution are satisfactory enough to be virtually indistinguishable from the original." Speaking of transmitting still-frame images in a reasonable length of time and at a reasonable cost, they were limited by the current state of technology, but not by failing to use available technology creatively. We now have the tools they lacked; we must analyze alternatives and apply them. First, define the clinical problem. Determine the minimum acceptable function level of the proposed teleradiology system. Then use your best judgement to sort our convenience, reliability, cost, and various other considerations in light of the needs of your practice. As you develop the scenario, frequently refocus on the problem to be solved. Very likely you will find, as you look closer at current options, that by using teleradiology you could increase the quality of service to your patients by extending your presence electronically to areas where constant physical presence is simply not possible, affordable, or convenient. PMID- 1599729 TI - Computer-based radiological teaching programs: the challenge and trauma of development and implementation. AB - Computers are becoming an invaluable part of the radiologist's environment whether they are used as a source of the patient's clinical or laboratory information, to store x-ray or pathologic reports or as a viewing station for films. The use of computers in the educational environment is but a natural extension of the increased computerization of the radiologic department. This article reviews the use of personal computers in a teaching environment via the construction of the computed tomography teaching program entitled "CT: The Game." The decisions that must be made in terms of hardware and software prior to program development as well as the actual development are discussed. The potential of computers in terms of continuing education as well as in residency training programs is discussed with the potential for the future addressed. PMID- 1599730 TI - Literature databases for radiologists. AB - There are two new computerized radiology literature databases available for those practitioners who require a more sophisticated retrieval system than the Index to Imaging Literature published annually by Radiology. The installation and use of these two products, the floppy disk based PC MASS and the CD-ROM based SilverPlatter Radiology are discussed. The advantages and disadvantages of both desktop programs are compared with the Index and to the telecommunication access of large general medical databases such as MEDLINE. PMID- 1599731 TI - Automatic screening of plain film mammography. AB - Using the computer as a diagnostic tool is a normal everyday function of modern radiology departments with CT, MRI, and ultrasound. This article describes the preliminary results using the computer as a coworker in a diagnostic scrutinizing process. Conventional analogous mammographic films were digitized and analyzed. Promising results were obtained detecting microcalcifications, dense areas, and their borderlines and stellate configurations. There are problems with detecting skin changes, probably caused by insufficient digitizing. PMID- 1599732 TI - Computer-aided diagnosis: development of automated schemes for quantitative analysis of radiographic images. AB - Preliminary results obtained with computer-aided diagnosis (CAD) from various radiographic examinations are very encouraging. However, CAD is still at an early stage of its development. It will be necessary to increase further the understanding of image features of normal and abnormal patterns, to establish databases, and to devise specific approaches for particular types of pathology. Although the existing schemes are designed to be applied to digital radiographs, similar techniques can be applied in the future to cross-sectional images such as CT, MRI, and ultrasound. We believe that CAD will become clinically practical in the near future. PMID- 1599733 TI - Computers in Radiology--revisited. PMID- 1599734 TI - Microcomputers and database software for monitoring quality assurance activities. AB - A description of how one community hospital implemented a successful quality assurance program in radiology with the use of a personal computer and relational database management software is presented. The system has been well received and is easy to use and maintain. There are aspects of quality assurance beyond the double-reading method that are not addressed by this system. However, as we learn more about different quality assurance programs, the system has the capacity to evolve. The advertising literature is flooded with information about software packages that claim to meet all Joint Commission quality assurance requirements. Therefore, it is prudent to avoid making hasty purchasing decisions to accomplish a quick-fix solution to managing quality assurance activities. The Joint Commission recommends a systematic approach to defining needs and evaluating vendor products or services. PMID- 1599735 TI - Radiological application of three-dimensional imaging systems. AB - Three-dimensional displays are becoming more frequent in medical imaging. As PACS and imaging workstations as nodes on networks provide greater ease and availability of three-dimensional reconstructions of digital data applications are increasing. Applications at this time are limited to high-contrast structures. In CT these are complex fractures or deformities. Three-dimensional display clarifies the anatomy and facilitates operative planning. In MRI, MR angiography is the principal application. The ability to rotate the data set in three dimensions eliminates potential overlap, increasing the sensitivity and specificity of the technique. Three-dimensional imaging is becoming available for scintigraphic and sonographic studies but applications have not yet been clarified. PMID- 1599736 TI - A research and development strategy for the NHS. PMID- 1599737 TI - Teenage conception and contraception in the English regions. AB - Nationally available data on teenage fertility, family planning care and mortality were analysed to determine the relationship between teenage conception, availability of abortion and family planning care, and an indicator of socioeconomic disadvantage--the Standardized Mortality Ratio (SMR). In the 14 regions of England the strongest correlate of teenage conception and of the proportion of teenage conceptions aborted was female all-causes SMR. High levels of provision of NHS abortion services and uptake of family planning clinic care did not significantly reduce teenage fertility. Provision of traditional family planning services obviously plays an important role in preventing teenage pregnancy, but innovation in this service coupled with a concerted effort to reduce social disadvantage might have a greater impact on teenage fertility in England. PMID- 1599738 TI - Marital status: association with social and economic circumstances, psychological state and outcomes of pregnancy. AB - We examined the association of marital status with economic, social and psychological factors and with the outcomes of pregnancy (defined as onset of labour, type of delivery, live and still births and birthweight). The study population was 1431 white women consecutively booking for antenatal care. Birth registrations were inspected. Of 278 women who were unmarried during pregnancy, 61 per cent were cohabiting, 26 per cent were living with adults other than the father and 13 per cent were living alone. Compared with the married women, unmarried women overall were, on average, younger, less educated, of lower social class, in poorer economic circumstances, more dependent on state support and less satisfied with their living arrangements. Irrespective of age and social class, they were less likely to have planned the pregnancy, more likely to smoke and drink, to book later for antenatal care and to miss more appointments. In general, unmarried women were more likely to have some indication of depression and to experience more serious life events during the pregnancy. Controlling for age and social class, the categories 'married', 'cohabiting' and 'on their own' showed significant trends from best to worst. Those living with adults other than the father showed intermediate results. There were no significant effects of marital status, controlled for age and social class, and associated social, economic and psychological circumstances on outcomes of pregnancy. Forty-one per cent of births to women on their own, 35 per cent to women living with other adults and 11 per cent to women cohabiting during pregnancy were registered by only one parent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599739 TI - Education for public health medicine. PMID- 1599740 TI - Time spent in hospital by children as a health care indicator: inter-district comparisons. AB - It has been widely recommended that children should be admitted to hospital only if treatment cannot be provided at home, and that durations of hospital stay should be minimized. We have used record linkage to calculate a statistic which is not yet commonly available, the total time spent in hospital by children per year, and have compared this between six districts in the Oxford Region. Hospitalization rates for children who stayed a total of two days or less per year in hospital increased over time; rates for children who stayed more than two days declined. Mean and median total days spent in hospital varied between districts but, in absolute terms, the differences were small at less than one day's difference between districts per year per child admitted. Inter-district variation decreased over time, although the variation in use of day case care which remained suggests that some districts could still do more work in this fashion. PMID- 1599741 TI - Time spent in hospital by the elderly in the final year of life as a health care indicator: inter-district comparisons. AB - We have studied the amount of time spent in hospital by elderly people in their final year of life in 1976, 1981 and 1986 in six districts covered by the Oxford record linkage study to determine the extent of differences between districts. There was consistent but insubstantial variation between the districts. Variation declined over time, suggesting that the use of hospital care for the elderly may, in this respect, be nearing consensus. We conclude that the measure of total time spent in hospital by the elderly in their last year of life was not a powerful discriminator between districts in this region. When record linkage is implemented elsewhere in England, it will be possible to make wider geographical comparisons to determine whether important variations exist elsewhere. PMID- 1599742 TI - Cost-effective screening strategies for colorectal cancer. AB - This paper models a range of feasible strategies for mass population screening for colorectal cancer. It uses both clinical and economic data derived from the major colorectal cancer screening trial currently under way in Nottingham, supplemented by data from concurrent Scandinavian trials. Costs and yields for 12 strategies are modelled, and optima are identified according to a number of evaluation criteria. The cost-effectiveness condition for the desirability of introducing a programme of colorectal screening is also established. PMID- 1599743 TI - An old-style public health perspective of present-day health problems in a black peri-urban area of South Africa. AB - The public health philosophy of the earliest Medical Officers of Health is as relevant today as it was in the middle of the last century. The social, economic and environmental conditions, together with the historical and cultural background of a community are all worthy of study when assessing health care needs. This paper describes the high-density peri-urban black communities in Natal and KwaZulu that surround the City of Durban, South Africa, and outlines an 'alternative health strategy' that has been developed to meet their specific needs. PMID- 1599744 TI - The introduction of a computerized system for notification and improved analysis of infectious diseases in Sheffield. AB - In 1989 the manual system of recording and analysing notifications of infectious disease in Sheffield was replaced by a computerized system based on the Epi Info software package. An analysis of the costs and benefits of this change shows that there has been a one-off cost of 780-930 h spent in developing the system. Offset against this is a continuing saving of time of around 400 h per annum. Other benefits which are harder to measure are enumerated and discussed. Costs of computer hardware and software are not substantial in comparison with the savings in staff time. PMID- 1599745 TI - Salmonellosis associated with 'Combi-oven' cooked egg. AB - During July 1989, four cases of Salmonella enteritidis (later identified as PT24) infection were reported by laboratories in Bristol. All those infected had dined at a restaurant in the city. An epidemiological investigation revealed that a number of restaurant staff and 56 customers who had completed a questionnaire had also been ill with gastrointestinal illness. An association was found between illness and eating egg mayonnaise. A 'Combi-oven' egg-cooking technique has been identified as the most likely cause of this outbreak. In view of the widespread commercial use of this cooking method the evidence related to this outbreak is given in detail. PMID- 1599746 TI - An outbreak of hepatitis A: school toilets as a source of transmission. AB - An outbreak of hepatitis A associated with a Middle school involved 23 cases; 17 were pupils attending the Middle school, one was a teacher, one was a relative of a case, and four were from the associated First school, of whom three had siblings in the Middle school. The probable source case was a male pupil infected by a sibling who had contracted hepatitis A while abroad on holiday. A questionnaire survey and salivary IgG and IgM anti-HAV testing of the pupils demonstrated a statistically significant association between infection and the use of a changing room toilet for defecation. An inspection of the school showed that toilets lacked toilet paper, soap and hand towels. Advice was given to pupils, parents and staff on hygiene. Human normal immunoglobulin was administered to susceptible family contacts, pupils and staff at the school. The school outbreak might have been prevented if the source case for the school had been given immunoglobulin when his sibling developed hepatitis A. PMID- 1599747 TI - A restaurant-associated outbreak of E. coli O157 infection. AB - An outbreak of haemorrhagic colitis due to Escherichia coli O157 and associated with a restaurant in Lothian, occurred in September 1990. There were 16 symptomatic cases, four of whom (all children) required dialysis. Notable features of the outbreak were the wide range of incubation periods (1-14 days), the occurrence of secondary spread through asymptomatic carriers and the prolonged period (at least seven days) during which the restaurant appears to have been the source of infection. Despite careful investigation, no single source within the restaurant was identified. The implications for public health are discussed. PMID- 1599748 TI - Quarterly communicable disease review July to September 1991. From The PHLS Communicable Disease Surveillance Centre. PMID- 1599749 TI - The pill and mortality--an overview. PMID- 1599750 TI - Smoking among children in the European community. PMID- 1599751 TI - Absence of HIV-2 in Spanish groups at risk for HIV-1 infection. PMID- 1599752 TI - Synergy between human monoclonal antibodies to HIV extends their effective biologic activity against homologous and divergent strains. PMID- 1599753 TI - Biological markers associated with prolonged survival in African children maternally infected by the human immunodeficiency virus type 1. AB - Sixteen children over the age of 5 years (Group 1) have been identified out of 537 children infected by human immunodeficiency virus and born to HIV-infected mothers, in Kigali, Rwanda. They were followed up for 2 years and compared with 16 younger AIDS patients (Group 2) and with 16 age- and gender-matched HIV-1 seronegative children (Group 3). Fourteen Group 1 subjects had anti-HIV-1 IgM which persisted during the entire study period, in 11 cases directed to HIV-1 envelope proteins. In vitro, immortalization of B lymphocytes by the Epstein-Barr virus confirmed a high production of IgM to envelope proteins. All these patients had anti-p 17 IgG which was not observed in 7 patients from Group 2. All 16 children mounted significant titers of neutralizing antibodies to HTLV-IIIB, and, in 8 patients tested, against two other HIV-1 strains, RII and MN. HIV-1-specific major histocompatibility complex (MHC)-restricted cytotoxic T cells were demonstrated in 3 of 5 of the subgroup who were tested. Prolonged survival over 5 years in children with maternally acquired HIV-1 infection is associated with a high titer of neutralizing antibodies, a persistent production of IGM to HIV-1 envelope proteins and of IgG to p 17. PMID- 1599754 TI - Thermodynamic and kinetic analysis of sCD4 binding to HIV-1 virions and of gp120 dissociation. AB - Kinetic and thermodynamic aspects of the binding of sCD4 to intact virions of human immunodeficiency virus type 1 (HIV-1 RF), and of the subsequent induction of gp120 dissociation were studied. sCD4 binding to virions at 4 and 37 degrees C is half-maximal at approximately 40 and 10 nM, respectively. The transition between low-affinity and high-affinity binding of sCD4 to virions occurs over a narrow temperature range between 20 and 25 degrees C. Shedding of gp120 from virions after sCD4 binding is also temperature dependent, being initiated above approximately 20 degrees C. The minimum temperatures for the sCD4 affinity transition and gp120 shedding are, therefore, similar and we suggest how the two processes might be related mechanistically. PMID- 1599755 TI - Cytokine augmentation of HIV-1 LTR-driven gene expression in neural cells. AB - The induction of human immunodeficiency virus type 1 (HIV-1) gene expression by cytokines was investigated in cells of central nervous system origin. These were human neuroblastoma, glioblastoma, and astrocytoma cell lines, a murine oligodendroglioma and primary murine astrocyte cultures. The cytokines used were tumor necrosis factor alpha (TNF alpha), interleukin-1 beta (IL-1 beta), IL-6, and interferons alpha and gamma (IFN alpha, gamma). Transient transfection of cells with a chloramphenicol acetyltransferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) showed significant augmentation following treatment by particular cytokines. TNF alpha was found to augment HIV LTR-directed CAT activity in all cell types. IL-1 beta also activated the HIV LTR reporter gene in glioblastoma, astrocytoma, and astrocyte cells. IL-6 enhanced HIV gene expression in one example only, the primary astrocyte cultures. The interferons generally suppressed expression from the LTR except IFN gamma which produced a twofold rise in the murine glial cells and IFN alpha augmenting expression in one neuroblastoma cell line. No synergy was observed between pairs of activating cytokines tested. The HIV tat gene product was found to be functional in all cells, cotransfection of a tat expression vector transactivating expression from the LTR, with varying degrees of efficiency. In some cell lines the combination of an activating cytokine and tat resulted in an enhancement above that obtained by cotransfection of tat alone. In others, the level of CAT activity did not significantly change. Analysis of nuclear extracts from cytokine-treated cells further implicated the involvement of NFKB in the induction of HIV-1 gene expression.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599756 TI - No direct neuronotoxicity by HIV-1 virions or culture fluids from HIV-1-infected T cells or monocytes. AB - Macrophages and microglia are the principal target cells for human immunodeficiency virus (HIV) in brain, and as such, are likely participants in the neuropathology of HIV infection. In a model system for this process, we found that fluids from human monocyte cultures enhanced survival and differentiation of the neurons in fetal rat brain explants. In contrast, fluids from HIV-infected monocyte cultures were strongly toxic to neurons and paradoxically enhanced the proliferation of glial cells. Further, neuronotoxic activity in these fluids was mediated through activation of NMDA binding receptors on the neurons and was inhibited by any of several different NMDA antagonists. Neuronotoxic activity was directly related to contamination of the HIV virus stock with Mycoplasma arginini and M. hominis. Pure cultures of mycoplasma, bacterial lipopolysaccharide (LPS), or murine recombinant tumor necrosis factor alpha (rTNF alpha) each induced neuronotoxicity which exactly mirrored that induced by the contaminated HIV stock. It is likely that mycoplasma or components of the mycoplasma plasma membrane stimulate TNF alpha production by the glial cells in the brain explants. Indeed, careful depletion of glial cells in these explants prevented mycoplasma or LPS-mediated neuronotoxicity. No neuronotoxicity was evident with HIV-1 virus stock, HIV-1 gp120, or culture fluids from HIV-infected T cells or monocytes when these preparations were free of contamination by mycoplasma and LPS. These findings suggest caution in interpretation of those experiments in which similar contamination has not been rigorously excluded. PMID- 1599757 TI - The replicative restriction of lymphocytotropic isolates of HIV-1 in macrophages is overcome by TGF-beta. AB - In vitro exposure of human blood monocyte-derived macrophages to T-cell tropic human immunodeficiency virus (HIV) isolates fails to establish a productive viral infection. Several studies have shown that such preferential HIV-1 replication in T cells or in mononuclear phagocytes (HIV tropism) may be determined by distinct viral characteristics. In the present study it was demonstrated that transforming growth factor-beta (TGF-beta), a factor known to be produced by platelets, macrophages, and other cells present at a wound site, can act as a mediator in overcoming the lymphocytotropic restriction of several well-characterized viral isolates of HIV-1 (i.e., LAV, Z84, pLAI, NY5). Macrophages infected with these isolates show cytopathic changes comparable to those seen upon infection with the monocytotropic isolate ADA. To achieve this effect with TGF-beta, the factor must be present after the infection period. The emerging virus retains its original cellular tropism. Based on these observations the authors propose a role for TGF beta in the establishment and progression of HIV infection and disease. PMID- 1599758 TI - Effect of serum components on syncytium formation and virus production by cells infected with human immunodeficiency virus in vitro. AB - Previously it has been reported that cocultivation of human immunodeficiency virus type 1 (HIV-1)-infected cells with uninfected cells results in formation of multinuclear giant cells, generated via an interaction of gp120 on the surface of infected cells with CD4 on the uninfected cells. Formation of multinuclear giant cells as occurring in the presence of normal fetal calf serum was not observed when HIV-infected MOLT-4 or MOLT-3 cells (chronically infected with HTLV-IIIB) and uninfected cells were cocultured in both serum-free medium and fibrinogen depleted serum. Addition of sera (human and rabbit) as well as of fibrinogen (human and bovine), fibronectin (human), and alpha-globulin (human), but not of albumin, transferrin or gamma-globulin to serum-free medium caused formation of multinuclear giant cells. In contrast, HIV production from MOLT-3 cells proceeds also in the absence of serum. In control experiments it was established that the cells maintained at reduced serum concentration, or in serum-free medium without or with fibrinogen are viable even though displaying a lower metabolic rate (ATP formation and DNA synthesis). From these findings we conclude that serum components (e.g., fibrinogen, fibronectin, and alpha-globulin) are absolutely required for syncytium formation but are not essential for virus release. PMID- 1599759 TI - Influence of human recombinant interferon-alpha and interferon-gamma on bone marrow progenitor cells of HIV-positive individuals. AB - As a result of a pathophysiologically unexplainable bone marrow failure, most patients with progressive stages of human immunodeficiency virus (HIV) infection develop anemia, leukopenia, and thrombocytopenia. Besides the possibility of immune-mediated cytolysis or of direct viral infection of hemopoietic progenitor cells, the inhibitory influence of cytokines, for example interferon-alpha (IFN alpha) and IFN-gamma, on hemopoiesis of HIV-infected patients might be considered as one parameter that contributes to myelosuppression. Therefore, progenitor cells from the bone marrow of HIV+ and HIV- persons were exposed to increasing concentrations of recombinant human IFN-alpha and IFN-gamma in methylcellulose assays. The colony formation of pluripotent (CFU-GEMM), erythroid (BFU-E), and granulocyte-macrophage (CFU-GM) progenitor cells was inhibited by both interferons. The 50% inhibitory doses (ID50) of IFN-alpha were 125.6 U/mL and 131.5 U/mL for BFU-E from HIV-infected persons and normal controls, respectively; the corresponding ID50 of IFN-alpha for CFU-GM growth was 1095.8 U/ml and above 3000 U/ml. When IFN-gamma was studied the ID50 was 341.7 and 2794.6 U/ml for BFU E from HIV-infected and healthy individuals, respectively, while the ID50 for CFU GM was above the highest dose levels in both groups (greater than 3000 U/ml). The ID50 for CFU-GEMM was below the lowest dose levels of IFN alpha and IFN gamma tested in both groups (less than 10 U/ml). The inhibitory effects could be specifically neutralized by monoclonal antibodies against IFN-alpha and IFN gamma, thus confirming that the suppressive effects were due to the cytokines used. PMID- 1599760 TI - [Continuous monitoring of the upper esophageal sphincter with the Dent device, during acid perfusion or distension with balloon of the esophageal body]. AB - The aim of the present study was to evaluate pressure changes of the UES under conditions that simulate the effects of gastroesophageal reflux (GER), that are, balloon esophageal distension and acid perfusion 0.1 N. Studies were performed in eight healthy subjects and fourteen patients with reflux esophagitis (RE), divided in two groups according to symptoms, 6 patients with heartburn and 8 patients with heartburn and regurgitation. We have employed the Dent sleeve to monitor UES pressure. The catheter was located with the help of a side-hole manometric catheter placed in the opposite side of the Dent sleeve; thereafter, it was anchorated. Perfusion of acid at 5 and 10 cm below the UES induces a pressure increase statistically significant, (paired data). This pressure increase is shown when mean values of the 5 minutes are considered as well for every minute. On the after hand, esophageal balloon distension did not produce pressure increases in any of the groups. PMID- 1599761 TI - [Response of the upper esophageal sphincter to various esophageal stimuli in patients with reflux esophagitis]. AB - The clinical symptoms, including oropharingeal dysphagia and bronchial symptoms, have been analyzed in 18 normal controls and in 48 patients with reflux esophagitis. Patients with reflux and pyrosis and regurgitation usually have a disease of longer duration, more bronchial symptoms, greater severity of endoscopic lesions and less pressure in the U.E.S. area than those who only have heartburn. In 10 normals as well as in 28 patients (15 with pyrosis and 13 with both pyrosis and regurgitation) the pressure behavior of the superior esophageal sphincter has been studied with a specially designed instrument after different stimuli: acid perfusion at 5 and 10 cm of the U.E.S. during 5 minutes and esophageal balloon distention at 10 cm. In normal individuals none of the stimuli modified the pressure at rest of the U.E.S., while in patients with reflux esophagitis only HCl perfusion at 5 cm was able to significantly increase pressure. This finding was independent of the clinical symptoms of the patients. PMID- 1599762 TI - [Correlation between dysplasia and malignization risk of Crohn disease]. AB - The malignancy risk in Crohn's disease is less than that of ulcerative colitis, although it has not been so well studied. The possibility of an early detection of malignant changes during the long term follow-up of the patients induces to look for parameters which might be helpful in this respect. In the second surgical clinic of the Hospital Clinico in Madrid, the pathological findings of 11 patients with the diagnosis of Crohn's disease have been analyzed and correlated with the clinical findings. The evaluation of the degree of dysplasia was done on 15 samples obtained by endoscopy and compared with the findings of the surgical specimens in 6 operated patients. The degree of dysplasia increases with age of the patients and years of evolution of the disease with a significant correlation (p less than 0.001) between negative dysplasia and positive dysplasia grade I. PMID- 1599763 TI - [Digestive hemorrhage caused by aorto-duodenal fistula. Report of 5 cases]. AB - The aortoduodeonal fistula is a rare condition and has high mortality. We report five retrospective cases of digestive hemorrhage due to an aortoduodenal fistula (4 secondary and 1 primary) between 1986 and 1990. Three of them died. Attention is called to the importance of clinical suspicion and the main diagnostic methods in early diagnosis such as oral endoscopy. We also enhance the importance of emergency surgery for survival. PMID- 1599764 TI - [Appendicular endometriosis. Clinicopathologic study of 12 cases]. AB - Endometriosis of the Digestive Tract is an uncommon pathology, especially when ileocecal appendix is involved. Authors report twelve cases of appendiceal endometriosis reviewed from surgical and anatomopathological records. The preoperative diagnosis is almost impossible. The most usual clinical presentation is compatible with that of acute or chronic appendicitis. The definitive diagnosis is confirmed by anatomopathological study of the surgical specimen. The Surgical treatment consists of appendicectomy alone or associated with extirpation of other concomitant neighbouring lesions. PMID- 1599765 TI - [Treatment of residual choledochal calculi in patients with Kehr's T drainage: role and results of endoscopic sphincterotomy]. AB - The results of sphincterotomy in the treatment of residual gallstones after cholecystectomy in a series of 62 patients, bearers of a T tube are reported. The mean time after surgery was 26.4 +/- 19.2 days. The procedure was technically successful in 59/62 (95.1%). Stones were passed spontaneously or were retrieved in 55/62 patients (88.7%). In four patients gallstones persisted in spite of sphincterotomy. All were operated with favorable results. Complications were observed in 4 patients (6.4%), without mortality. Sphincterotomy is a safe and relatively efficient technique in the treatment of cholecystectomized patients with residual gallstones and a T tube drainage. PMID- 1599766 TI - [Accessory spleen: ultrasonographic and tomographic characteristics]. AB - The failure of fusion of splenic tissue results in the formation of accessory spleens. This entity normally appears in post-mortem examinations. The purpose of this work was to determine the incidence of the accessory spleen and to compare the ultrasonographic and tomographic features of the accessory spleen and the main spleen in a group of one thousand patients affected with several abdominal pathologies. Five hundred of these patients were studied by ultrasonography and five hundred patients by computed tomography. The ultrasonographic and tomographic features of the accessory and main spleen were similar. Its diagnosis is specially important in certain groups of patients with hematologic disease or abdominal trauma with splenic tear. This is due to the fact that the hypertrophy of the accessory spleen can produce a relapse of the disease. PMID- 1599767 TI - [Isoenzyme profile of alkaline phosphatase in patients with pancreatitis]. AB - In patients with pancreatitis an increase of the total amount of alkaline phosphatase (ALP; EC 3.1.3.1) and the appearance of its macro isoenzyme which parallels the decrease of bone isoenzyme was found. This isoenzymatic profile suggests that the increase of ALP in pancreatitis is due to the concomitant hepatobiliary disorder. Moderate increases of ALP didn't appear to be related to the existence of gallstones. PMID- 1599768 TI - [Eosinophilic gastroenteritis: review of the published cases in Spain and comparison with foreign literature]. AB - We review the Spanish literature on Eosinophilic Gastroenteritis. The data are compared with those of several foreign series. Abdominal pain, vomiting, diarrhea, and abdominal distension due to ascites were the most frequent clinical manifestations. In our country most cases had ascites. A history of allergy was reported by less than on half of patients. Peripheral eosinophilia with otherwise normal laboratory findings is the rule. However, peripheral eosinophilia was not essential for diagnosis, since it was absent in one quarter of patients. Small intestine barium studies were abnormal almost always, but the findings were not specific. The diagnosis is based on the endoscopic and/or peroral gastrointestinal biopsy. However, a false negative diagnosis can occur, since the disease can take up a patchy distribution, or a more profound involvement of the gastrointestinal layers without mucosal disease. The treatment of choice is corticosteroids, with a spectacular therapeutic response. Complete studies with biopsies taken at multiple levels of the gastrointestinal tract, are necessary to ascertain the extent and depth of the disease. The etiology is unknown, and although allergy causes can be elicited in some cases, they are absent in the majority of them. We encounter no essential differences in the eosinophilic gastroenteritis characteristics in our country in relation to other countries. PMID- 1599769 TI - [Brown bowel syndrome: diagnostic and therapeutic problems]. AB - A new case of a brown bowel syndrome is presented in a 27 year-old man, clinically with severe esteatorrhea of many years of duration, with moderate pancreatic exocrine insufficiency and intestinal motility disorders suggesting a functional change secondary to a deposit of lipofucsin. We comment the pathogenic, diagnostic and therapeutic implications related to this circumstance. PMID- 1599770 TI - [Biphasic viral hepatitis "A" associated with autoimmune phenomena]. AB - Acute hepatitis A virus infection (HAV) is a benign, self limited disease with infrequent extrahepatic features unlike the hepatitis B or the nonA-nonB virus infection. We describe the case of a 37 year old white woman with HAV who had a relapse with a second elevation of the alanine aminotransferase level together with joint pain, skin lesions, angioneurotic edema, and autoantibodies (ANA, anti smooth muscle, antiparietal gastric cells). The liver biopsy showed piecemeal and early bridging necrosis. She had a rapid reversal of her clinical, biochemical and histological abnormalities. As far as we known, this is the first reported case of autoantibodies or angioneurotic edema associated with HAV. We comment on the pathogenesis of this rare association. PMID- 1599771 TI - [Splenic abscess]. AB - Splenic abscess is rare and may be present either as a localized area in the spleen or as part of a generalized sepsis. A 35 year old man presented with a two month history of anorexia, weight loss, fever, abdominal pain and arthralgia. Multiple abscesses localized in the spleen were diagnosed by CT and splenectomy was performed. PMID- 1599772 TI - [Duplicated and ectopic giant megaureter in asymptomatic adult and benign intraperitoneal cysts]. PMID- 1599773 TI - [Lymphoma of the esophagus in patient with HIV infection]. PMID- 1599774 TI - [Rupture of aneurysm of the proper hepatic artery]. PMID- 1599775 TI - [Ceftriaxone and blood coagulation in cirrhotic patients]. PMID- 1599776 TI - [Quality assurance--a practical example. Improved quality of home nursing services]. PMID- 1599777 TI - [Norwegian Nurses' Association's project: training in quality assurance]. PMID- 1599778 TI - [Consequences of errors in handling of drugs--for the patient, the community, the physician and the nurse]. PMID- 1599779 TI - [Ethic in health services. Medical ethics and limitations for nursing ethics]. PMID- 1599780 TI - [Chronic pulmonary insufficiency. Long-term treatment with low-dose oxygen]. PMID- 1599781 TI - [Sexuality--the forgotten dimension in nursing]. PMID- 1599782 TI - [Care for the elderly: Katz' ADL-index--a nursing tool]. PMID- 1599783 TI - [Geriatric care. Psychopharmaceuticals for problem behavior in senile dementia- do we know what we are doing?]. PMID- 1599784 TI - [Geriatric care. I became a stranger!. Interview by Rolf Sorli]. PMID- 1599785 TI - [Geriatric care within Vesthold community. Professional similarities and differences]. PMID- 1599786 TI - [Chronic pulmonary insufficiency. Oxygen treatment of patients]. PMID- 1599787 TI - [Nursing and self-confidence]. PMID- 1599788 TI - [Build a bridge between theory and practice--and start with the students!]. PMID- 1599789 TI - [Why men do not stay in nursing]. PMID- 1599790 TI - [Epilepsy]. PMID- 1599791 TI - [Skin disinfection before insertion of peripheral venous catheter. Why not do the right way?]. PMID- 1599792 TI - [Chronic pulmonary insufficiency. Long-term care using home oxygen therapy. Follow-up of patients in Oslo]. PMID- 1599793 TI - [Oxygen therapy. "Otto" gave me life. Interview by Siv Barstad]. PMID- 1599794 TI - Interaction of phospholipids with rhodamine 6G in toluene. AB - Upon interaction of various glycerophospholipids with Rhodamine 6G in toluene, a typical difference spectrum with an absorption maximum at approximately 515 nm is obtained . This spectrum is obtained with phosphatidylcholine only after treatment with NaCl, which presumably weakens intra- and/or inter-molecular electrostatic binding between the negatively charged phosphate moiety and the protonated nitrogen in this molecule. Absorption at 515 nm was linear for all of the phospholipids investigated from a concentration of approximately 1.2 microM up to at least 50 microM. The highest extinction coefficient was obtained for diphosphatidylglycerol (251 mM-1 cm-1) and all of the compounds tested, with the exception of phosphatidylethanolamine, demonstrated extinction coefficients higher than that of palmitic acid. Thus, the absorption spectrum which results from the interaction of purified glycerophospholipids with Rhodamine 6G in organic solvent is a sensitive measure of the amount of phospholipid present. PMID- 1599795 TI - Resolution and absolute stereochemistry of 6,7-dimethoxy-4-phenyl- 1,2,3,4 tetrahydroisoquinoline. The crystal structure of the R-hydrochloride salt form. AB - Stereospecific multistep synthesis and resolution of 6,7-dimethoxy-4- phenyl 1,2,3,4-tetrahydroisoquinoline (3) has been achieved from its racemic base. The absolute configurations of the optical antipodes converted into their hydrochloride salt forms have been determined by X-ray diffractometric analysis, thus permitting assignment of the antipodes as the (+)-(4R)-3 and (-)-(4S)-3 enantiomers. The crystal structures of the two enantiomers are related as mirror images and only the (4R)-3.HCl form has been fully determined by three dimensional X-ray diffraction. In the solid state, the carbon atoms of the two methoxy groups deviate slightly from the benzene-ring plane and the chirally oriented phenyl substituent is almost perpendicularly tilted out of conjugation with the isoquinoline system. Examination of the enantiomers in several biochemical tests for 5-HT, NE and DA uptake inhibition-activity revealed an exclusive preference for the (4S)-enantiomer. These results are in accord with previous suggestions that the S-configurational state of the 4-phenyl substituent is important for biological activity. PMID- 1599796 TI - Synthesis of a potential bifunctional mimic of transaminases. AB - As a potential bifunctional mimic of transaminases 3,7-dimethyl-10-[3-(4- aminomethyl-5-hydroxy-6-methyl-3-pyridyl)propyl]-3,7,10- triazatricyclo[3.3.3.0(1,5)] undecane (I) has been synthesized by attaching 3,7 dimethyl-3,7,10-triazatricyclo [3.3.3.0(1,5)]undecane (II) to a pyridoxamine nucleus via an all-carbon chain. The chain length between the pyridine ring and II is restricted to three atom units so that the possibility for II to act bifunctionally during the transamination is maximized. In its protonated form, the nitrogen closest to the pyridine ring cannot deliver the proton intramolecularly to the alpha-carbon of the developing amino acid. To make the synthetic route generally applicable, introduction of the side-arm base is arranged at a later stage of the synthesis so that different di- or poly-amines can easily be used in place of II to prepare other target molecules that might possess bifunctional catalytic activity. This arrangement also greatly reduces the polarity and water-solubility of the intermediates and the purification of these compounds thus becomes much easier. The method of introducing the amino functionality at the C-4 methylene group described herein provides an alternative to that currently in use (reduction of oximes). PMID- 1599797 TI - Stereoselective synthesis of the alpha-allyl C-glycoside of 3-deoxy-D-manno-2 octulosonic acid (KDO) by use of radical chemistry. AB - Methyl 2-C-allyl-2,6-anhydro-3-deoxy-4,5:7,8-di-O-isopropylidene-D-glycero- D talo-octonate (9a), the protected alpha-allyl C-glycoside of 3-deoxy-D-manno-2 octulosonic acid (KDO), has been synthesized using a photochemically initiated radical reaction. A phenyl thioglycoside (8) was used as the substrate and allyltributyltin as the acceptor. The stereoselectivity of the reaction was 90:10 in favour of the talo-isomer (alpha-). PMID- 1599798 TI - Synthesis of 5-alkoxymethyl derivatives of 3'-amino-2',3'-dideoxyuridine and evaluation of their activity against HIV and cancer. AB - 5-Alkoxymethyluracils 2a-c have been prepared by acid-catalyzed etherification of 5-hydroxymethyluracil (1). Compounds 1, 2a-c, 5-methoxymethyl- and 5 benzyloxymethyl-uracil were silylated and coupled with 1,5-di-O-acetyl-3 phthalimido-2,3-dideoxy-beta- D-erythro-pentofuranose (3), in the presence of trimethylsilyl triflate as a catalyst, to give the corresponding 3'-phthalimido 2',3'-dideoxynucleosides 5a-f and 6 which on treatment with 33% methylamine ethanol afforded the corresponding 3'-amino-2',3'-dideoxynucleosides 7a-f and 8 in high yields. Compound 7d showed colony inhibition when tested against human epidermoid cervical cancer cells. Nucleosides 5a-e, 7a-f and 8 did not show any significant activity against HIV-1. PMID- 1599799 TI - Specific carbon-13 labelling of leucine residues in human growth hormone. AB - Biosynthetic human growth hormone specifically 13C-labelled in the carbonyl positions of all 26 leucine residues has been obtained by recombinant DNA techniques using 13C-labelled leucine and an E. coli strain that requires leucine. It is shown that, on the whole, the labelling is specific with no significant mislabelling as would have been the case had the 13C-labelled leucine been metabolized. PMID- 1599800 TI - The rational development of biological response modifiers. PMID- 1599801 TI - Treatment of gastrointestinal and renal adenocarcinomas with interferon-alpha. AB - Treatment of adenocarcinomas with interferon-alpha as a single agent has been disappointing. Recent efforts have focused on the combination of interferon with cytotoxic drugs such as 5-fluorouracil. A number of postulated mechanisms can explain synergistic interactions between 5-fluorouracil and interferon-alpha, including interaction with pyrimidine pathways, and alteration of drug metabolism. Previous studies in colorectal cancer, using 5-fluorouracil and interferon-alpha are reviewed, suggesting that the combination is more active than 5-fluorouracil alone. In renal cell carcinoma, the literature is reviewed, suggesting that daily interferon is the most efficacious schedule; preliminary data suggest that addition of 5-fluorouracil to interferon-alpha can double the expected response rate of 16% achieved by interferon-alpha alone. PMID- 1599802 TI - Strategies for improving antitumor activity utilizing IL-2: preclinical models and analysis of antitumor activity of lymphocytes from patients receiving IL-2. PMID- 1599803 TI - MTP-PE in liposomes as a biological response modifier in the treatment of cancer: current status. AB - MTP-PE in liposomes is a BRM which can be given relatively safely to patients with cancer. The maximum tolerated dose appears to be higher than the optimal dose inducing immunomodulatory effects such as cytokine induction and monocyte/macrophage activation. The most consistently induced cytokines measured in the plasma of patients a few hours after MTP-PE are TNF and IL-6. Indirect evidence supports the assumption that increased levels of TNF and IL-6 are signs of macrophage activation occurring in situ in tissues taking up liposomal MTP-PE shortly after injection. These tissues are mainly lungs, liver and spleen, as shown in 4 patients injected with radiolabelled liposomes containing MTP-PE. Assuming that activated monocytes and macrophages cannot eliminate gross tumor load, the main targets for MTP-PE are micrometastases after removal of the primary tumor. Thus, adjuvant treatment using liposomal MTP-PE in combination with chemotherapy is a major goal for the future. PMID- 1599804 TI - Clinical trials of bestatin for leukemia and solid tumors. AB - A new immunomodulating agent, bestatin (INN: ubenimex) has low toxicity after long-term oral administration and significantly modifies immunological responses. Prolongation of remission duration and survival was achieved in adult acute nonlymphocytic leukemia with bestatin immunotherapy combined with remission maintenance chemotherapy. Patients with myelodysplatic syndrome (MDS) and chronic myelogenous leukemia (CML) responded to bestatin, and it is noted that cytogenetic remission was obtained in CML. MDS and CML are thought to be a family of clonal malignant disorders in which malignant transformations occurs at the level of the pluripotent stem cell. Bestatin may be capable of modifying the biological-proliferative disequilibrium of the disease, and the therapy opens new and promising prospects in the treatment of both MDS and CML. Randomized controlled studies of bestatin immunotherapy were performed in solid tumors including malignant melanoma, carcinoma of the lung, stomach, bladder, head and neck, and esophagus, and therapeutic benefits on disease free-interval or survival were observed in certain types of these cancers. However, the adjuvant activity of bestatin immunotherapy for these cancers should be further investigated to confirm its activity. PMID- 1599805 TI - Development of immunotherapeutic strategies for the treatment of malignant neoplasms. AB - Focused preclinical studies have been used to gain insight into the mechanism of therapeutic activity of cytokines, growth factors and biological response modifiers (BRMs). These data can then be used to develop a clinical hypothesis to facilitate the development of these new biological drugs. In this manuscript, we discuss a number of preclinical and clinical studies using interferon-gamma, IL 2, and the colony stimulating factors. The importance of the systematic profiling of the biological activity of such biological drugs is emphasized and we discuss the utility of the mechanistic data in their clinical development. The overall preclinical approach identifies the cellular, biochemical or gene regulatory event that is associated with the therapeutic activity of a biologic and this surrogate (be it biological, chemical, or quality of life) is then used to optimize the clinical protocol in a phase 1b trial. This, in theory, results in the rapid identification of the optimal dose, schedule and route of administration for subsequent testing in a phase II/III clinical trial. PMID- 1599806 TI - Treatment of gout and crystal arthropathies and uses and mechanisms of action of nonsteroidal anti-inflammatory drugs. AB - Nonsteroidal anti-inflammatory agents have anti-inflammatory, analgesic, and antipyretic actions. Nonsteroidal anti-inflammatory drugs are the preferred class of agents for the treatment of gout and other crystal-induced arthropathies. The use of colchicine for other than the prophylaxis of acute attacks is discouraged owing to side effects, which include death. The inhibition of the enzyme prostaglandin H synthase by most nonsteroidal anti-inflammatory drugs explains many of their effects and toxicities. However, it is likely that additional biologic actions are important. These include the inhibition of the transcription of the gene for prostaglandin H synthase, a direct central effect on peripheral inflammation, and the modulation of the functions of a variety of cells (eg, neutrophils, lymphocytes, and chondrocytes). This review focuses on the current controversy in the treatment of gout and discusses the recent literature on the actions of nonsteroidal anti-inflammatory drugs. PMID- 1599807 TI - Toxicities of the nonsteroidal anti-inflammatory drugs. AB - There has been significant progress in defining the risks associated with the use of nonsteroidal anti-inflammatory drugs. There is now clear consensus that certain patient subsets are at an increased risk for gastroduodenal mucosal damage when those patients are treated with these drugs. The therapy for treating mucosal damage or preventing it has also been better defined. The studies published this year have provided a better understanding of those patients who should be considered as candidates for possible therapy for prophylaxis against mucosal damage and which drugs might be useful. The patients who are at risk to develop renal dysfunction remain less well defined. This paper reviews the current relevant literature. PMID- 1599808 TI - Current issues of methotrexate and cyclosporine. AB - Methotrexate given in weekly oral-pulse regimens is rapidly becoming the most popular of the antirheumatic drugs. It seems to act relatively quickly (within 6 to 8 weeks) and patients continue to take it for a longer period of time than other antirheumatic drugs. This issue of long-term hepatotoxicity still has not been clarified, and concerns are now being raised regarding increased infection rates and whether methotrexate should be stopped before joint replacement surgery. Methotrexate, however, remains a very easy drug to use, although in the future it will probably be used as part of combination therapy. Although several clinical trials have demonstrated efficacy for cyclosporine in active rheumatoid arthritis, problems with renal toxicity are still significant. The majority of patients exhibit a rise in the serum creatinine level, although this returns to a normal level when cyclosporine is ceased. In view of this, cyclosporine is likely to remain a drug used in selected, severe cases not responding to other agents. PMID- 1599809 TI - Immunosuppressive drug therapy for rheumatic disease. AB - The use of cyclophosphamide, chlorambucil, azathioprine, and 5-fluorouracil in managing rheumatic disease is reviewed. The major focus of recent studies has been the treatment of lupus or systemic vasculitis. Long-term studies of treatment of lupus nephritis have provided additional data regarding the efficacy of regimens containing cyclophosphamide and the predictive value of renal biopsies in determining outcome. Related studies of alkylating agents in idiopathic membranous nephritis suggest that they may have a role in severe disease. Studies of immunosuppression in severe systemic vasculitis are reviewed. Controlled studies have shown that pheresis is probably not effective in this illness and suggest that the addition of cyclophosphamide to prednisone improves the control of disease activity. PMID- 1599810 TI - Novel immunomodulating and immunotherapies, and novel therapies and strategies for inflammatory arthropathy. AB - During the past year, another disease possibly influenced by intravenous gammaglobulin was identified as dermatomyositis/polymyositis. Additional studies provided further information regarding the use of monoclonal anti-CD4 antibody and combination therapy in rheumatoid arthritis, antithymocyte globulin in scleroderma, and intravenous gammaglobulin in juvenile rheumatoid arthritis. New therapeutic horizons also emerged including the novel immunosuppressant FK-506, the removal of disease incitants by medical arthroscopy, antiarthritic T-cell receptor V beta-specific antibodies, and the potential of achieving tolerance via peroral administration of autoantigens. PMID- 1599811 TI - Glucocorticoid therapy for rheumatic diseases. AB - Glucocorticoids are an essential therapeutic agent in the management of many inflammatory, autoimmune, and other rheumatic diseases. Perhaps because of their remarkable potency and widespread use, the literature on steroid treatment has tended to be rather anecdotal. Nonetheless, new information, both on the mechanism of action and on the clinical application, continues to become available. The complexity of the biology of steroid-receptor engagement and gene regulation is unraveling, and carefully designed clinical studies are helping to refine clinical application. However, for the clinician, the need for careful observation and sound judgment with glucocorticoid use remains critically important. PMID- 1599812 TI - Pathophysiology and principles of pain management in rheumatic diseases. AB - Pain is a major presenting symptom in patients with rheumatic diseases. It is difficult, however, to define pain precisely because there are both objective and subjective components to the experience of pain. Thus, patients with the same degree of tissue inflammation may experience different levels of pain. The variation in individual pain experience often presents us with a diagnostic and therapeutic dilemma. Pain management, therefore, must be based on a solid understanding of the pathophysiology of pain and on a careful review of the risks, benefits, cost, and efficacy of available treatments. PMID- 1599813 TI - The role of infectious agents in the etiopathogenesis of rheumatoid arthritis. PMID- 1599814 TI - The immunogenetic component of susceptibility to rheumatoid arthritis. AB - The precise nature of the HLA element associated with rheumatoid arthritis has been identified as a short sequence of amino acids on the alpha helix of a range of DR beta alleles. Recently the range of alleles known to bear this sequence and to be associated with rheumatoid arthritis has increased considerably. Although these findings lend further weight to the validity of the original hypothesis, they have also made it very difficult to propose a mechanism for the association. It has also become clear that the simple model of dominant susceptibility is unsatisfactory. Patients with early disease show little or no association with any HLA alleles, whereas patients with severe forms of rheumatoid arthritis are frequently homozygous for DR4, showing a disproportionate tendency toward compound heterozygocity--expressing two different molecules sharing the conserved sequence. PMID- 1599815 TI - Mechanisms of tissue destruction and cellular activation in rheumatoid arthritis. AB - Rheumatoid arthritis is a chronic inflammatory disease of unknown etiology that is marked by synovial inflammation and destruction of articular extracellular matrix. Several studies of the pathogenesis of tissue destruction have focused on the production of metalloproteinases and their inhibitors in synovium as determinants of joint preservation. Also, the role of cytokines in the perpetuation of synovitis and of superantigens in synovial T-cell activation have led to novel hypotheses that attempt to explain abnormalities of synovial structure and function in rheumatoid arthritis. Recent studies that dealt with these topics are briefly reviewed in the context of current paradigms of inflammatory synovitis. PMID- 1599816 TI - Assessment and prognosis of rheumatoid arthritis. AB - Efforts continue to identify and consistently utilize those clinical, laboratory, imaging, and other features of rheumatoid arthritis that best reflect the disease process and its impact on individual patients. We seek descriptions that are accurate, reproducible, simple, sensitive, and predictive. Such assessments will lead to development of prognoses for individual patients and to more rational patient management. The past year has witnessed reemphasis of health status indexes (instruments) and other simple approaches to clinical assessment of patients, eg, use of standardized grip strength, button test, walk time, and modified articular indexes. Computed tomography and magnetic resonance imaging provided clinically important and otherwise unappreciated (but expensive) information about joint integrity and inflammatory disease with sensitivity and resolution considerably beyond conventional techniques. Laboratory assessment of patients included consideration or reconsideration of the utility of measurements of C-reactive protein, rheumatoid factors, immune complexes, complement receptors and complement activation products, antiperinuclear factors, trace elements, interleukins and interleukin receptors, soluble cell surface receptors, lymphoid cell phenotypes, and synovial immunohistology; all are important in the pathogenesis of rheumatoid arthritis and all have contributed variably to predicting patient outcomes. None were shown to be more clinically informative than erythrocyte sedimentation rate or C-reactive protein. The variables that have been associated with unfavorable prognosis for rheumatoid arthritis are also discussed. We hope that continued study will lead to identification and adoption of simple assessments that will prove to be powerful predictors of good or poor patient outcomes and stratification of patient risk. This uniform measure of disease assessment will improve judgments of potential benefits of therapeutic interventions. PMID- 1599818 TI - Bone biochemistry and physiology from the perspectives of the vitamin D endocrine system. AB - Vitamin D plays an indispensable role in the dual processes of bone formation (mediated by osteoblasts) and bone resorption (mediated by osteoclasts). More recently, researchers have confirmed the existence of a vitamin D endocrine system, which is responsible for describing the "sphere of biological influence" of vitamin D3. In that system, the kidney serves as the endocrine gland that produces 1,25-dihydroxyvitamin D3. This hormonally active form of vitamin D3 generates many, if not all, of the biologic responses attributed to the parent vitamin D3, including its role in bone formation and bone resorption. In addition, 1,25-dihydroxyvitamin D3 is able to generate biologic responses via both genomic and nongenomic pathways. The classic nuclear receptor for 1,25 dihydroxyvitamin D3 is present in more than 30 target tissues. This paper reviews evidence for the critical role of 1,25-dihydroxyvitamin D3 in cell differentiation, particularly of hematopoietic cells, as well as in the generation of the bone resorptive cell--the osteoclast. In the past year, much evidence has been accumulated supporting the claim that 1,25-dihydroxyvitamin D3 tightly regulates differentiation of osteoclast progenitors into osteoclasts. Osteoclast progenitors are believed to be derived from the monocyte-macrophage lineage. However, the generation of new osteoclasts is modulated by osteoblastic stromal cells, which are one of the target cells for the nuclear actions of 1,25 dihydroxyvitamin D3. PMID- 1599817 TI - New horizons in the medical treatment of rheumatoid arthritis. AB - To date, the medical management of rheumatoid arthritis has been less than optimal for a significant number of patients. This has been manifested by progressive deformity, functional disability, and increased mortality in these patients. Alternative treatment schedules of currently available drugs, as recently advocated by some investigators and the results of both the preclinical and the applied clinical evaluations of a number of novel pharmacologic therapies are reviewed. Several effective nonpharmacologic treatments have been reported in the last year, and their significance in the treatment of rheumatoid arthritis are also discussed. PMID- 1599819 TI - Hypercalcemia and parathyroid disorders. AB - Primary hyperparathyroidism and malignancy are responsible for the majority of reported cases of hypercalcemia. Suspected hypercalcemia should be documented on more than one occasion, preferably with the measurement of ionized calcium. Determination of intact parathyroid hormone with a modern two-site immunoassay is the single most important laboratory analysis in the differential diagnosis of hypercalcemia. Intact parathyroid hormone is increased or inappropriately high in primary hyperparathyroidism and suppressed or low normal in hypercalcemia of malignancy. Midregion and carboxylterminal radioimmunoassays are less effective in separating parathyroid and nonparathyroid hypercalcemia. In malignancy, hypercalcemia may result from local osteolysis or humoral factors. Although ectopic parathyroid hormone is produced rarely and certain lymphomas secrete 1,25 dihydroxyvitamin D, parathyroid hormone-related protein is elevated in the majority of patients with humoral hypercalcemia of malignancy. Recent developments in the measurement of parathyroid hormone-related protein should help to define the physiologic function of parathyroid hormone-related protein and its role in the differential diagnosis and therapy of hypercalcemia. PMID- 1599820 TI - Renal osteodystrophy, disorders of vitamin D metabolism, and hypophosphatasia. AB - Recent advances in renal osteodystrophy deal with the pathogenesis of the disease, in particular in early renal failure, with the mechanisms of skeletal resistance to parathyroid hormone, with the potential role of iron, and with increased knowledge of adynamic bone disease. For the control of phosphatemia, aluminum-containing phosphate binders are more and more avoided, whereas calcium acetate or carbonate are more and more prescribed. X-linked hyphophosphatemia continue to cause great interest as well as the various iatrogenic osteomalacias. PMID- 1599821 TI - Epidemiology, etiology, and diagnosis of osteoporosis. AB - Osteoporosis is a major cause of morbidity among the elderly; more than 40% of women will suffer from fractures by the time they reach the age of 70. Recent research has focused on the determinants of postmenopausal osteopenia and of postmenopausal osteoporosis. The bone density of elderly people may depend on peak bone mass in adolescence, and recent studies have tried to define the respective roles of genetic factors, nutrition, and exercise in the attainment of peak bone mass. Maintenance of bone mass throughout adult life may be influenced by different factors: the potential role of thiazides in preserving bone density in elderly patients has been suggested; the deleterious effects of steroid therapy on the skeleton has been confirmed, and new information on the course and pathogenesis of steroid-induced osteopenia has been uncovered. Some reports have expressed concern over the possible adverse effects of L-thyroxine therapy on skeletal integrity, whereas others present reassuring data. The importance of bone mass measurements in predicting who is at risk for osteoporosis has been confirmed, and preliminary screening guidelines have been proposed. PMID- 1599822 TI - Treatment of osteoporosis. AB - No new compounds were tested in 1991, but more results on available therapeutic options were accumulated. Bisphosphonates and calcitonins appeared to increase bone density when used for a period of 1 to 3 years and to decrease vertebral fracture rate. Estrogen replacement therapy is still the most effective prevention of postmenopausal bone loss. Various studies revealed that the risk of inducing breast cancer has not been established and that estrogen has a strong protective effect against cardiovascular mortality. Screening for osteoporosis at menopause to target estrogen replacement therapy to women at increased fracture risk is recommended. Calcium and vitamin D supplements proved to be of significant value, especially in elderly people, in whom they even decreased fracture incidence. Fluoride demonstrated variable bioavailability. This might explain why certain fluoride studies showed fast increases in bone density with heavy side effects but no effect on fracture rate, whereas fluoride preparations of lower bioavailability were better tolerated and decreased fracture incidence. For almost all drugs, some dose dependence was demonstrated and maximally tolerated doses were established, but minimal effective doses are still unknown. Vertebral fracture rate was more often included as the final criterion in therapeutic trials, whereas long-term effects on hip fracture incidence still need more attention. PMID- 1599824 TI - Clinical therapeutics. PMID- 1599823 TI - Paget's disease of bone and fibrous dysplasia. AB - This review discusses recent studies of the etiology and epidemiology of Paget's disease of bone, as well as studies of its complications and associations. Medical and surgical treatments are reviewed; agents used in the medical treatment of Paget's disease include pamidronate and other bisphosphonates, gallium nitrate, and plicamycin, among others. The article concludes with a review of various investigations of fibrous dysplasia. PMID- 1599825 TI - Rheumatoid arthritis. PMID- 1599826 TI - Metabolic bone disease. PMID- 1599827 TI - AIDS in Latin America and the Caribbean: current situation. PMID- 1599828 TI - Follow-up on cholera vaccine evaluation. PMID- 1599829 TI - Acute colorectal ischemia after aortic surgery: pathophysiology and prognostic criteria. AB - Acute colorectal ischemia is a rare though potentially lethal complication of aortic surgery. We reviewed our recent experience with 16 cases in order to analyze its causative and prognostic factors. The incidence was 2.8%, and the inferior mesenteric artery was occluded in all cases. All patients also had severe occlusive disease of at least two of the hypogastric or deep femoral arteries. Hypoperfusion due to arterial ligation, prosthetic occlusion or embolism was responsible in half the cases. Ischemia and perfusion due to aortic cross-clamping or perioperative hemorrhage were involved in the rest of the cases. Postoperative mortality was 31%. The mortality was lower for partial, nontransmural necrosis, and for elective operations. Recurrent intestinal ischemia, transmural necrosis, surgery for ruptured aneurysm, intestinal hemorrhage and pulmonary edema were associated with a higher mortality rate. All patients with anuria or extrarenal epuration and hepatic cytolysis died. Although reconstruction of the inferior mesenteric artery might lessen the incidence of postoperative colonic ischemia due to hypoperfusion, the role of oxygen free radicals should be investigated in humans, in order to afford colonic protection against the consequences of ischemia-reperfusion. PMID- 1599830 TI - High coincidence of inguinal hernias and abdominal aortic aneurysms. AB - Weakness in the musculotendinous barrier of the abdominal wall leads to inguinal herniation. Fiber degeneration by increased metabolism has been described recently as a causative factor. In previous investigations heightened elastase was detected in abdominal aneurysms. In order to investigate a possible relationship between hernias and abdominal aneurysms, patients scheduled for infrarenal aneurysm repair were examined for history of inguinal hernia. The prevalence of inguinal hernias (n = 49; 41%, p less than .001) in 119 patients with abdominal aneurysms was significantly elevated, compared to 81 patients with aortic occlusive disease (n = 15; 18.5%) and 298 patients with coronary artery disease (n = 54; 18.1%). Additionally, the number of patients with recent hernia repair (n = 19; 16%) or still awaiting repair (n = 11; 9%) was very high in the patient group with abdominal aortic aneurysms. Smoking habits were not different among all groups. We conclude that the prevalence of inguinal hernias in patients with abdominal aortic aneurysms is high compared with those with peripheral arterial occlusive disease or coronary atherosclerosis. These findings indicate a systemic fiber degeneration. PMID- 1599831 TI - Improved carotid hemodynamics with vertebral reconstruction. AB - This study tests the hypothesis that vertebral artery reconstruction improves carotid distribution hemodynamics during carotid occlusion. Twelve patients with vertebrobasilar symptoms underwent either direct (9) or indirect (3) vertebral reconstruction. There were six proximal vertebral to common carotid reimplantations, one proximal carotid-vertebral bypass and two distal carotid vertebral bypasses, all with saphenous vein. Three patients with carotid subclavian or axillo-axillary bypasses performed for symptomatic vertebral steal were studied at the time of carotid endarterectomy. During temporary ipsilateral carotid occlusion, vertebral reconstruction increased carotid back pressure from 39.3 +/- 10.2 mmHg to 46.8 +/- 9.5 mmHg (p less than 0.0001), increased cerebral perfusion pressure from 33.4 +/- 10.8 mmHg to 41.0 +/- 9.1 mmHg (p less than 0.0001), decreased the carotid collateral resistance to cerebral vascular resistance ratio from 1.68 +/- 0.90 to 1.24 +/- 0.64 (p less than 0.001), and increased the ratio of carotid back pressure to mean systemic arterial pressure from 0.452 +/- 0.122 to 0.515 +/- 0.118 (p = 0.0005). These results are presumed due to increased posterior-to-anterior blood flow in the posterior communicating arteries. Direct or indirect vertebral reconstruction may be a consideration in patients with cerebral ischemic symptomatic and nonreconstructible carotid occlusive disease. PMID- 1599832 TI - Diagnostic value of automatically interpreted oculopneumoplethysmography. AB - The diagnostic value of the Gee-oculopneumoplethysmography test for the detection of hemodynamically significant carotid artery obstructions has frequently been questioned due to the rather low agreement with arteriography. The kappa corrected diagnostic accuracy of this test has been reported to be in the range between 0.54 and 0.68. These values indicate a "fair to good" agreement with arteriography. One of the causes for this rather low agreement is the variability in the interpretation of oculopneumoplethysmography recordings. Automatic analysis of oculopneumoplethysmography recordings might minimize the risks of misinterpretation and might improve the clinical significance of the Gee oculopneumoplethysmography test. By assessing the signals of a conventional Gee oculopneumoplethysmography apparatus in a personal computer, this automatic analysis has been realized. In a clinical study (population of 85 patients) the diagnostic value of automatic analysis of oculopneumoplethysmography recordings has been evaluated. The automatically interpreted Gee-oculopneumoplethysmography test had a kappa-corrected diagnostic accuracy of 0.71 on a "per side" base and of 0.76 on a "per patient" base. PMID- 1599833 TI - Risk of prophylactic contralateral carotid endarterectomy. AB - Fifty-eight patients underwent a prophylactic contralateral carotid endarterectomy following an initial endarterectomy for symptomatic (38 patients) or asymptomatic (20 patients) carotid stenosis. No deaths occurred after either operation. Two (3.4%) minor neurologic deficits occurred after the initial operation and two (3.4%) major and two (3.4%) minor deficits occurred after the prophylactic contralateral carotid endarterectomy. Sixteen (28%) of the initial endarterectomies were associated with perioperative hyper- or hypotensive episodes compared to 35 (60%) of the prophylactic contralateral carotid endarterectomies (p less than 0.001). We did not document an increased risk of surgery in patients undergoing prophylactic contralateral carotid endarterectomy soon after the initial operation. All four neurologic events following a prophylactic contralateral carotid endarterectomy occurred when the operation was performed more than five weeks after the initial endarterectomy. The incidence of perioperative hyper- or hypotension was similar in patients undergoing prophylactic contralateral carotid endarterectomy less than or greater than five weeks after the first operation. Our results suggest that a prophylactic contralateral carotid endarterectomy may be associated with a higher incidence of neurologic complications and hyper- and hypotensive episodes than the initial carotid endarterectomy. Waiting more than five weeks to repair a contralateral asymptomatic carotid stenosis may not enhance the safety of the operation. PMID- 1599834 TI - Chronic histologic changes after vascular clamping are not associated with altered vascular mechanics. AB - The mechanical properties of arteries, along with the histologic and scanning electron microscopy characteristics of the nonatherosclerotic canine arteries, were investigated six months after vascular clamping. Different vessel clamps were applied to 73 sites on the carotid and femoral arteries in five anesthetized dogs. Each clamp was applied for 30 minutes with (a) sufficient force to just occlude blood flow or (b) as tightly as the clamp could be placed. After six months the vessels were excised, filled with barium sulfate suspension, and pressurized in 25 mmHg steps up to 150 mmHg. High resolution contact radiographs were taken at each pressure. These were magnified 35x and measured. Scanning electron microscopy and conventional histology disclosed that the clamped sites exhibited serrated clamp "tracks" in the intima, intimal hyperplasia, and, in a few cases, fractured elastic lamellae. These histologic changes were seen more frequently in the femoral artery than in the carotid artery (p less than .01). The mechanical properties, as determined from radiographic measurements, demonstrated that, for all types of clamps, the luminal diameter, pressure diameter relationship, and compliance of the clamped vessels were not significantly different from nonclamped control regions (ANOVA). These studies demonstrate that careful application of clamps to nonatherosclerotic arteries produces persistent morphologic changes, but these are not associated with altered mechanical properties of the vessel wall. PMID- 1599835 TI - Behcet's disease revealed by double peripheral arterial involvement. AB - We report the case of a 62-year-old man with Behcet's disease revealed by double aneurysmal involvement of the posterior tibial and popliteal arteries. The diagnosis was suggested because of repeated phlebitis, buccal aphthous ulcerations, and results of human leukocyte antigen gene typing. The different arguments leading to the diagnosis of Behcet's disease and appropriate treatment are presented. PMID- 1599836 TI - Bilateral infrapopliteal artery aneurysms. AB - The authors report the case of a 37-year-old man with bilateral posterior tibial artery aneurysms and concomitant collagen vascular disease. The patient initially presented with pain and swelling of the calves. The diagnosis was made by duplex scan and confirmed with arteriography. Diagnostic studies later verified the presence of a lupus-like syndrome. To date, 10 patients with aneurysms of the infrapopliteal arteries have been reported in the literature; four of these have had associated systemic diseases. These reports are reviewed; their clinical manifestations are discussed, and a treatment plan for these uncommon lesions is presented. PMID- 1599837 TI - Retrieval of Greenfield filter from the right atrium. AB - A Greenfield prematurely discharged in the right atrium (tricuspid valve) was retrieved by double snare technique with minimal modification (shortening) of the carrier through the initial internal jugular venotomy incision. PMID- 1599838 TI - Persistent hypoglossal artery: An anomaly leading to false-positive carotid duplex sonography. AB - Duplex ultrasonography is becoming increasingly popular as the sole diagnostic test in the evaluation of carotid artery bifurcation disease. We present a patient with a persistent hypoglossal artery, a rare primitive internal carotid basilar anastomosis, masquerading as an internal carotid artery stenosis on ultrasound. The operative management of this anomaly is reviewed. PMID- 1599839 TI - Jacques Oudot and his contribution to surgery of the aortic bifurcation. PMID- 1599840 TI - Hepato-left renal artery bypass. PMID- 1599841 TI - Conical endocaval filters with metallic struts: search for a new model. AB - The multitude of caval filters now available and conflicting experimental and clinical findings indicate that no one model can be considered to be perfect. The principal drawbacks of conical endocaval filters, such as the Greenfield model, are the possibility of migration and tilting, often related to failure to open, or untimely ejection of the filter. In this study, we analyzed the geometrical aspects of these filters, leaving aside all concerns of biocompatibility and thrombogenicity, as well as the hemodynamic or clinical aspects. The goal was to determine an ideal geometrical model, with optimal filtration of clots and low risk of tilting. PMID- 1599842 TI - Global programme on AIDS. Recommendations for the selection and use of HIV antibody tests. PMID- 1599843 TI - Smoking and mortality from cardiovascular diseases. PMID- 1599844 TI - Higher HIV rates in South European women. PMID- 1599845 TI - RCN nursing update: the will to learn. PMID- 1599846 TI - Nurses and the media. Turn your radio on. PMID- 1599847 TI - Politics: new kids on the block. PMID- 1599848 TI - Helping midwives in developing countries. PMID- 1599849 TI - Mental illness: support for relatives. AB - A questionnaire-based evaluation of a support group for relatives of people with mental illness living in the community is described. Set up initially in 1987, the evaluation suggests that the group has succeeded in offering emotional support to most members, although others have ceased to attend. The authors recommend that regular support of carers should become an integrated part of community mental health services. PMID- 1599850 TI - Making the case for good nursing care. PMID- 1599851 TI - Infection control. Hygienic hand decontamination. AB - Hygienic hand decontamination is the single most important technique available to nurses in preventing the spread of infection. The evaluation of hand decontamination is now recognised as a complex task that involves frequency, choice of agent, appropriate timing, duration and quality of technique. This article analyses each of the components of hygienic hand decontamination, and concludes that more research is necessary before evaluation of this vital nursing activity can be undertaken with confidence. PMID- 1599852 TI - Defining the nurse's role in outpatients. PMID- 1599853 TI - A day in the life. Bum notes and old records. PMID- 1599854 TI - Lateral nursing: fighting hearsay is heresy. PMID- 1599855 TI - Psychiatry: little shock of horrors. PMID- 1599856 TI - Asymptomatic carotid atherosclerosis study: role of the clinical coordinator. AB - This article introduces the reader to the role of the clinical coordinator in the Asymptomatic Carotid Atherosclerosis Study. The main responsibility lies in recruiting patients into the study and managing their follow-up period very closely for the next three to five years. Each coordinator is vital to its individual center in order to actively participate in this multicenter trial. PMID- 1599858 TI - Hand arterio-venous malformation. PMID- 1599857 TI - Postpartum ovarian vein thrombophlebitis: etiology, diagnosis, treatment, and nursing implications. AB - This article presents a review of the literature on postpartum ovarian vein thrombophlebitis with special emphasis of nursing implications. The technology of real time ultrasound, duplex Doppler ultrasound, computerized axial tomography, and magnetic resonance imaging now offer reliable methods for confirming a suspected diagnosis of postpartum ovarian vein thrombophlebitis. However, it may well be nurses in clinical settings who assess the often vague signs and be the first to alert the physician. Nurses have an important role in the prevention of postpartum ovarian vein thrombophlebitis. Prevention may be successful by teaching women holistic prenatal care including how to avoid infections during pregnancy and postpartum, and by practicing meticulous technique during pregnancy, labor and delivery, and postpartum. PMID- 1599859 TI - Preservation of arm veins for arterial reconstruction. AB - The results of surgery for lower extremity salvage have improved steadily over the past decade. One of the principles accounting for this advance is the preferential use of autogenous veins for peripheral bypass surgery. Nonautogenous and prosthetic grafts to the infrageniculate (below knee) level have patency rates significantly lower than autogenous bypasses. Currently, the technical limits of bypass surgery often depend upon the availability of adequate venous conduits. The saphenous vein has been the conduit of choice for distal arterial bypasses. However, some patients lack saphenous veins as a result of previous vein harvesting for coronary or other arterial surgery, phlebitis, variations in venous anatomy, previous vein stripping, or other conditions. In these patients, arm veins (cephalic and basilic) have been used successfully for limb salvage. There are several requirements for the successful use of arm veins. These include a detailed knowledge of the anatomy of the cephalic and basilic veins, education of patients and health care professionals, nursing protocols to preserve arm veins, and the training of surgical nurses in the demanding technical maneuvers for arm vein implantation. This paper will address these subjects. PMID- 1599860 TI - Vascular rehabilitation update. PMID- 1599861 TI - An amputee critical path. AB - Approximately 115,000 lower extremity amputations (50 per 100,000 in the general population) were performed in 1985. Successful rehabilitation of these patients is contingent upon comprehensive coordination of in-patient care and education of patients and families, coupled with effective discharge planning and follow-up. In an environment that places emphasis on shortened length of stay, an efficient method to a unified multi-disciplinary approach is more difficult than ever to accomplish. "Critical Pathways" are an effective tool to expedite the communication and planning required to achieve a timely discharge as well as successful rehabilitation. PMID- 1599862 TI - Behavioral and affective manifestations of brain tumours in children: a unit management perspective. AB - Brain tumors are second only to leukemia as the most common type of childhood cancer. Often, one of the first signs of underlying brain mass is change in the usual behaviour of the child. Disruptive and aggressive behaviour is not unusual especially with temporal lobe lesions, and poses a unique challenge to unit nurses. In this paper, a review of the current literature related to this topic will be reviewed. Some typical behavioral and affective responses of children with temporal lobe tumors will be outlined and patient management strategies will be discussed, from a nursing unit perspective. Finally, other nursing implications and future research possibilities will be discussed. PMID- 1599863 TI - Multiple sclerosis and alternative medicine. PMID- 1599864 TI - Trends in the care and treatment of patients with increased intracranial pressure. AB - The care and treatment of patients with known increased intracranial pressure (ICP) is one of the most challenging, important and many times difficult task a neuroscience nurse faces in the critical care setting today. Advances in technology have allowed for more precise ways of measuring ICP and with these advances, nursing care has become increasingly complex requiring quick, effective decision making and a high level of expertise for the nurse caring for these patients. The research in this area remains relatively new and the unanswered questions still tend to outweigh the conclusive findings. The research has really just begun, but what research has been done provides us with useful information in helping to provide a plan of care that can be implemented with relative success. The purpose is to review the trends in the care and treatment of patients with increased ICP over the past five years and evaluate their effectiveness based on the literature reviewed. It will also provide a basic review of the relevant physiological principles of increased ICP as related to the above case and treatment. PMID- 1599865 TI - Vasospasm after aneurysmal subarachnoid hemorrhage: a review of pathophysiology. AB - Ischemic brain injury, including infarction, continues to cause major morbidity among operated and non-operated survivors of aneurysmal subarachnoid hemorrhage. Following an introductory description of cerebral vessel pathology, the relationship between angiographic vessel narrowing, or "spasm", and focal clinical deficits attributed to the resulting ischemia is explored. The role of nimodipine is presented with respect to its impact on survival quality. The session concludes with an outline of directions for future research. PMID- 1599866 TI - Occupational health in the new NHS. PMID- 1599867 TI - Relations between occupation, smoking, lung function, and incidence and mortality of chronic non-specific lung disease: the Zutphen Study. AB - Information gathered in the "Zutphen study", the Dutch contribution to the Seven Countries Study was used for the present study. Follow up data from 1965 to 1 July 1985 were used. During this follow up, the morbidity state of the participants was verified at regular intervals. In 1965 lung function was measured by spirometry and the vital capacity (VC) and forced expiratory volume in one second (FEV1) were available. A complete set of data was available for 668 men. The occurrence of chronic non-specific lung disease (CNSLD) at a specific time was coded by one physician, using strict criteria. Information about the cause of death was obtained and coded by one physician in 1985. Occupation was coded and a distinction between blue and white collar workers was made. For the analysis of the relation between age, lung function, smoking habits, and occupational state with CNSLD incidence and mortality, proportional hazard models were used. Blue collar workers had a significantly raised risk for incidence of CNSLD only. The hazard ratio for blue v white collar workers with CNSLD mortality was 1.4 but not statistically significant. It was concluded that occupation is clearly related to incidence of CNSLD. There were indications that occupation is related to mortality from CNSLD. A reduced FEV1 was a strong predictor of both CNSLD incidence and mortality. It is noteworthy that small differences in age and height standardised lung function were significantly related to incidence of CNSLD, mortality from CNSLD, and total mortality. Although these differences in lung function have no direct clinical importance for the individual subject, they indicate a raised morbidity and mortality risk for the population. PMID- 1599868 TI - Lung function and radiographic signs of pulmonary fibrosis in oil exposed workers in a cable manufacturing company: a follow up study. AB - Thirty seven workers employed for at least three years in oil impregnation of cables during 1963-83 were followed up in 1990 to study the development of pulmonary fibrosis and consequences for lung function. They had been exposed to concentrations of mineral oil vapours of 50-100 mg/m3, and concentrations of oil mist of 0.5-1.5 mg/m3. All 29 living persons were traced. For each person one control matched for age, height, and smoking habits was selected. Among 25 workers followed up with radiographic studies, 10 cases of pulmonary fibrosis were found, by contrast with one case in the control group (p less than 0.01). Chest radiographs from 1979-80 and 1989-90 were reviewed. The profusion of small opacities increased in seven of 16 persons during 10 years without exposure. Seventeen workers had lung function tests. The bellows function (VC, FEV1, MVV) and lung volumes (TLC, RV) did not differ from those in the matched controls (p greater than 0.05), but the carbon monoxide transfer factor (TLCO) was decreased. The largest reduction of TLCO (1.5 mmol/kPa/min) was found among workers exposed for 10 years or more (p less than 0.05). Arterial blood gases were not affected at rest, but during maximum tread mill exercise, PO2 and HbO2 were reduced in exposed workers compared with controls, particularly among those exposed for at least 10 years (p less than 0.05). Exposure to low viscosity oil mist and vapour is the most plausible cause of the fibrosis. Unaffected bellows function, reduced TLCO, and decreased arterial blood oxygen during exercise is compatible with peribronchiolar fibrosis. PMID- 1599870 TI - A case-control study of malignant and non-malignant respiratory disease among employees of a fiberglass manufacturing facility. AB - A case-control study was conducted to determine the influence of non-workplace factors on risk of respiratory disease among workers at the Owens-Corning Fiberglas plant in Newark, Ohio. Cases and controls were drawn from a historical cohort mortality study conducted on behalf of the Thermal Insulation Manufacturers Association (TIMA) of workers employed at Newark for at least one year between 1 January 1940 and 31 December 1963 and followed up to the end of 1982. The TIMA study reported a statistically significant increase in respiratory cancer (compared with national death rates). Interviews were completed for 144 lung cancer cases and 299 matching controls and 102 non-malignant respiratory disease cases and 201 matching controls. Unadjusted odds ratios (ORs) were used to assess the association between lung cancer or non-malignant respiratory disease and birthplace, education, income, marital state, smoking with a duration of six months or more, age at which smoking first started, and duration of smoking. Only the smoking variables were statistically significant. For lung cancer, of the variables entered into a conditional logistic regression model, only the smoking OR of 23.4 (95% CI 3.2-172.9) was statistically significant. For non-malignant respiratory disease no variables entered into the final model were statistically significant. Results of the interview portion of our case-control study clearly indicate that smoking is the most important non-workplace factor for risk of lung cancer in this group of workers. Smoking does not seem to play as important a part, however, for non-malignant respiratory disease. Prevalence of cigarette smoking at the Newark plant was estimated for birth cohorts by calendar year. Corresponding data for the United States were compiled from national smoking surveys. Prevalence of cigarette smoking for Newark in 1955 appears to be sufficiently greater than the corresponding United States data in 1955 to suggest that some of the previously reported excess of lung cancer for Newark based on United States mortality may be accounted for by differences in the prevalence of cigarette smoking between white men in Newark and those in the United States as a whole. PMID- 1599869 TI - Lung function in retired coke oven plant workers. AB - Lung function was studied in 354 coke oven plant workers in the Lorraine collieries (Houilleres du Bassin de Lorraine, France) who retired between 1963 and 1982 and were still alive on 1 January 1988. A spirometric examination was performed on 68.4% of them in the occupational health service. Occupational exposure to respiratory hazards throughout their career was retraced for each subject. No adverse effect of occupational exposure on ventilatory function was found. Ventilatory function was, however negatively linked with smoking and with the presence of a respiratory symptom or discrete abnormalities visible on pulmonary x ray films. The functional values were mostly slightly lower than predicted values and the most reduced index was the mean expiratory flow, FEF25 75%. The decrease in forced expiratory volume in one second (FEV1) was often parallel to that in forced vital capacity (FVC), but it was more pronounced for subjects who had worked underground, for smokers of more than 30 pack-years, and for subjects having a respiratory symptom. Pulmonary function indices were probably overestimated because of the exclusion of deceased subjects and the bias of the participants. PMID- 1599871 TI - Class specific antibodies in serodiagnosis of farmer's lung. AB - The aim of the present study was to determine which microbes and which immunoglobulin (Ig) classes should be included in tests to discriminate between patients with farmer's lung and reference persons. The sera of a group of farmer's lung patients and their spouses were measured for IgG, IgA, IgM, and IgE antibodies against a panel of farmer's lung microbes. The concentrations of IgG, IgA, and IgE antibodies were higher in patients compared with their spouses. The patients were generally positive for antibodies of several Ig classes whereas the spouses had only either IgG or IgA antibodies. A test comprising the determinations of IgG antibodies against T vulgaris and IgA antibodies against A fumigatus would correctly group 94% of the cases in the Finnish farming population. The selection of microbes for other environments needs to be determined locally. PMID- 1599872 TI - An updated mortality study of workers in three major United States refineries and chemical plants. AB - A historical cohort study of refinery and chemical plant workers, originally observed from 1970 to 1977, was updated to the end of 1982. This cohort included 25,321 active, retired, and terminated workers at the Exxon refineries and chemical plants in Baton Rouge, Louisiana; Baytown, Texas; and Bayway/Bayonne, New Jersey. An emphasis was placed on the cancers previously reported to be increased in at least one petrochemical worker population. The population included a high proportion of retirees, providing adequate work experience and latency to evaluate risks associated with employment. Vital status was determined for 98.3% of the population and death certificates were obtained for 99.9% of the decedents. Mortality for "all causes of death" (standardised mortality ratio (SMR) = 89, 95% confidence interval (95% CI) 87-91) and for "all cancers" (SMR = 94, 95% CI 89-100) were lower than expected based on state rates. History of cigarette smoking collected from individual medical records and summarised work histories were used for subgroup analyses. There was no indication that cancers of primary interest were increased; however, blue collar workers at one plant had raised rates of kidney cancer (SMR = 246, 95% CI 146-390), which may require further evaluation. PMID- 1599873 TI - Scintigraphy with J001X, a Klebsiella membrane glycolipid, for the early diagnosis of chronic berylliosis: results from an experimental model. AB - A glycolipid (J001X) isolated from the membrane proteoglycans of a non-pathogenic strain of Klebsiella pneumoniae was developed to bind selectively to macrophages. A scintigraphic technique could thus be developed and applied to an experimental model of lung berylliosis. Six baboons were injected intratracheally with a beryllium metal suspension. Three to 24 months later, they were submitted to both an anatomical and a functional respiratory evaluation. Two baboons were explored at the early stage of alveolitis and four baboons at a more advanced stage characterised by a granulomatous disorder. Scintigraphy was performed using J001X labelled with 99mtechnetium administered as an aerosol. In the six baboons, conventional imaging techniques (chest x ray film, computed tomography scan, gallium scintigraphy), failed to show either any lung abnormality or mediastinal lymph nodes consistent with beryllium disease. In the two recently contaminated baboons, J001X scintigraphy showed a well defined parenchymal fixation facing the contaminated lobe. In the four baboons who were at a more advanced stage of berylliosis, J001X fixation was always focused paratracheally without any significant involvement of the lung parenchyma. The subcarinal and laterotracheal lymph nodes seen at necropsy corresponded to J001X scintigraphic fixations. In conclusion, when compared with conventional techniques such as chest x ray film, computed tomography scan, magnetic resonance imaging, and gallium scintigraphy, J001X scintigraphy has proved its ability to detect occult lesions in experimental berylliosis in baboons. By comparison with gallium scintigraphy, scintigraphy with J001X appears to have superior sensitivity and can be performed in four hours. PMID- 1599874 TI - Relation between urinary beta-aminoisobutyric acid excretion and concentration of lead in the blood of workers occupationally exposed to lead. AB - Urinary beta-aminoisobutyric acid (ABA) concentration was determined by fluorometric high performance liquid chromatography in 22 workers occupationally exposed to lead. The urinary excretion of ABA was increased with increasing exposure to lead. The excretion of urinary ABA had a significant correlation with concentration of lead in blood (Pb-B) (r = 0.581), similar to the correlation of Pb-B with urinary delta-aminolaevulinic acid (ALA) concentration (r = 0.563). The determination of urinary ABA concentration in workers exposed to lead, therefore, may offer a new approach for evaluating the health effect of lead. PMID- 1599875 TI - A six year longitudinal study of the occupational consequences of drinking over "safe limits" of alcohol. AB - Although much research has focused on the psychological, social, and economic consequences of heavy problem drinking, there has been far less attention paid to the consequences of "moderate" drinking. This study used a unique opportunity to carry out a six year follow up of a cohort of male and female white collar workers in whom there was baseline information on alcohol consumption and access to details on sickness absence, labour turnover, and promotion. It has provided evidence that even moderate alcohol consumption in the working population is associated with social costs for the employer and the employee, including substantial sickness absence, and lack of promotion in men, although the increase in labour turnover was not statistically significant. The longitudinal examination of consumption in this study suggests that early intervention in a drinking career may reduce alcohol consumption and consequently avoid years of morbidity and sickness absence, as well as having a favourable influence on performance and labour turnover. PMID- 1599876 TI - Incidence of leukaemia and brain tumours in some "electrical occupations". PMID- 1599877 TI - Second Conference of the European Society for Analytical Cellular Pathology, Nijmegen, The Netherlands, 17-22 May 1992. Abstracts. PMID- 1599878 TI - Human smooth muscle myosin light chain-2 gene expression is repressed in ras transformed fibroblast cells. AB - We have previously characterized human smooth muscle myosin light chain (MLC)-2 isoform by complementary DNA cloning and have shown that this isoform is expressed in a number of nonmuscle cells such as fibroblast cells. In this report, we show that when human osteosarcoma derived clonal cells (TE 85 clone F 5) (HOS), which are immortalized and nontumorigenic, undergo transformation following infection by Kirsten murine sarcoma virus (K-HOS) or by a chemical carcinogen [N-methyl-N-nitro-N-nitrosoguanidine (MNNG-HOS)], the smooth muscle MLC-2 mRNA is repressed. Revertants of transformed K-HOS cells (K-HOS312H) show normal levels of smooth muscle MLC-2 mRNA. Transformation of HOS cells by Ha-ras oncogene sequences, either by retroviral infection or by transfection followed by selection for tumorigenic cells in nude mice, results in complete repression of smooth muscle MLC-2 mRNA level. Treatment of HOS cells with tumor promoting phorbol ester, 12-O-tetradecanoylphorbol-13-acetate, results in repression of smooth muscle MLC-2 mRNA. Smooth muscle MLC-2 mRNA level is repressed in many, but not all, transformed cell lines, suggesting that it is not an indirect consequence of transformation but is specific to the agent that brings about transformation. HOS cells synthesize three MLC-2 protein species resolved by the two-dimensional gel electrophoretic system. The identity of the smooth muscle MLC 2 isoform was established by coelectrophoresis of the in vitro synthesized MLC-2 protein corresponding to the cloned complementary DNA in the two-dimensional gel system along with total [35S]methionine labeled HOS cell proteins. Quantitative analysis of MLC-2 isoforms in different HOS cells indicates that the synthesis of smooth muscle MLC-2 isoform is specifically repressed to an undetectable level in ras transformed and MNNG transformed cells and also following treatment with 12-O tetradecanoylphorbol-13-acetate. PMID- 1599879 TI - System biomedicine: a new paradigm in biomedical engineering. PMID- 1599880 TI - Psychophysical experiments and a neural network model of binocular rivalry. AB - The alternation process in binocular rivalry was examined by psychophysical experiments. The stimulus strength to the central part of the visual field in one eye was varied while the stimulus strength in the other eye remained constant. The data obtained by the experiments indicate that the variations in stimulus strength alter the mean dominance duration, variance and predominance, and the frequency histogram of the dominance duration almost fits to the gamma distribution. To explain these results, a model which consists of neural elements receiving impulse trains with stochastic fluctuations is proposed and the experimental results are simulated on a computer using the model. Although the present model is restricted to explain only the rivalry between two lines which have different orientations, we could obtain agreement between the simulation results and the experimental results by giving appropriate values for some parameters of the model. PMID- 1599881 TI - Kinetics of respiratory and circulatory responses to step, impulse, sinusoidal and ramp forcings of exercise load in humans. AB - Transient responses of minute ventilation (VE), oxygen consumption (VO2), carbon dioxide output (VCO2), cardiac output (Q) and heart rate (HR) to step, impulse, sinusoidal and ramp changes in exercise load were studied in healthy human subjects at the moderate load range. Exercise was performed in the upright position using a bicycle ergometer. The transient responses to step and impulse forcings fitted essentially to a second-order model consisting of a fast and a slow component, while the responses to sinusoidal and ramp forcings fitted to a first-order model. No significant asymmetry was observed between the on- and off responses to step forcing. On the contrary, the mean response time (MRT = pure time delay + time constant) of variables to ascending ramp forcing was prolonged, while the MRT to descending ramp was shortened with decreasing ramp slope. The on and off asymmetry of the MRT was observed in VE, VO2 and VCO2 and, to a lesser extent, also in HR and Q. A non-linear blood flow model, which simulates changes in the wash-in and wash-out time of metabolic substances into and from the chemoreceptor, has been proposed as a likely explanation for the asymmetrical responses. It was concluded that the regulatory system of respiration and circulation might be essentially non-linear in its operation, despite the fact that the cardiorespiratory responses during exercise seemed to fit linear models. PMID- 1599882 TI - Development of a non-invasive transcutaneous blood glucose monitoring method using an ISFET biosensor. AB - A transcutaneous blood glucose monitoring method has been developed by combining an SOS/ISFET (silicone-on-sapphire/ion sensitive field effect transistor) biosensor with an SEF (suction effusion fluid) collecting technique. The SEF collecting cell has a stainless steel mesh at its bottom which is kept in a weak vacuum condition so as to suck up transcutaneous SEF and deposit it in a reservoir above. An ISFET biosensor, consisting of immobilized enzyme membranes, enables the detection of glucose concentrations in very small samples. The method has been successfully applied to non-invasive monitoring of human blood glucose levels during tests involving 75 g OGTT (oral glucose tolerance test). Glucose concentrations measured with SEF showed good correlation with those obtained directly from serum. Results suggest the feasibility of a portable blood monitoring system. PMID- 1599883 TI - New optical method for determination of antigen-antibody reaction using level crossing technique. AB - Presented here is a new method of optically detecting agglutination reactions through counting the number of level-crossings of light intensity fluctuations scattered by coated carrier particles. The theory behind this technique is that the number of level-crossings decreases as the size of aggregated particles and, accordingly, the antigen concentration increases. The antigen used in this experiment is immunoglobulin E (IgE). The crossing level is fixed at the average intensity of the scattered light. The detectable range is from 17 to 1000 IU/ml under this condition. The incubation time is 15 min. The coefficient of variations (CVs) of the number of level-crossings is reasonably low, between 0.382 and 3.05% (n = 5). Through simple data processing involving comparison of the data with the crossing level and counting the number of level-crossings, it is possible to determine the antigen concentration on a real time basis. PMID- 1599884 TI - A data reconstruction system for EEGs recorded on paper. AB - More efficient image skeletonization techniques can lead to a reduction in the distortion of EEG images and high precision of data reconstruction. We have developed and improved a system by which EEGs recorded on paper can be converted to computer treatable digital data. The performance of the system was evaluated and it was found to have excellent EEG data reconstruction ability. The system makes it possible to apply various computer analyses to EEGs recorded on paper. PMID- 1599885 TI - Demand for urological devices increases among aging population. PMID- 1599886 TI - 1991 Labat Lecture. The effect of local anesthetics on the peripheral vasculature. AB - The effects of local anesthetic agents on the peripheral vasculature are not uniform and not easily described. Factors governing these effects are as follows: the method of application (i.e., intravenously, intraarterially, or locally): When injected into the venous system, a stimulating effect (central nervous system effect) is usual, which dominates over a peripheral vasoconstriction effect; the concentration: Resistance to flow is reduced with high concentrations and vasoconstriction occurs with low concentrations; the target organ (e.g., skin, placenta, lungs, splanchnic bed, and spinal cord), which is significant; an anti-adrenaline-like effect; isomers, which can differ in their effect (mepivacaine, not bupivacaine). With these final comments I would like to conclude this presentation. I hope that it has been as stimulating for you as an audience as it has been for me in preparing it. I would again like to express my deep and sincere gratitude for the honor you have bestowed upon me and for the kind attention you have devoted to my lecture. PMID- 1599887 TI - Continuous pleural infusion of bupivacaine offers better postoperative pain relief than does bolus administration. AB - BACKGROUND AND OBJECTIVES: To determine whether continuous pleural analgesia offers better postoperative pain relief than does bolus administration in postcholecystectomy patients. METHODS: Eighty postcholecystectomy patients with a subcostal incision were randomly allocated to receive pleural analgesia with either a bolus regime of 20 ml 0.375% bupivacaine with 1:200,000 epinephrine at four-hour intervals (bolus group), or a loading dose of 20 ml 0.375% bupivacaine with 1:200,000 epinephrine immediately followed by a continuous infusion at a rate of 6 ml/hour during the first 24 hours postoperatively (infusion group). A 10-cm linear visual analog scale was used and recorded before performing pleural analgesia and at 1,6,12,18, and 24 hours subsequently. Plasma levels of bupivacaine were determined in eight patients of the infusion group. Samples were taken at 5,15,30, and 60 minutes and at 6 and 18 hours after the start of infusion. RESULTS: Mean visual analog scale values were significantly lower (p less than 0.001) at 6, 12, 18, and 24 hours in the infusion group. PaCO2 decreased significantly (p less than 0.001) after the block in both groups, with no difference between the groups. Plasma levels were well below toxic levels in the infusion group. CONCLUSIONS: Continuous pleural analgesia offers better postoperative pain relief than does bolus administration. Pneumothorax was observed in two patients during the study. PMID- 1599888 TI - An evaluation of epidural bupivacaine with and without meperidine in labor. AB - BACKGROUND: One aim of epidural analgesia during childbirth is to provide satisfactory pain relief with minimal side effects. We hypothesized that a combination of opioid and local anesthetic would better achieve this aim than either drug alone. This study compared the efficacy and side effects of epidural meperidine and bupivacaine combined to those of meperidine and bupivacaine alone. METHODS: One hundred consenting nulliparas requesting epidural analgesia in labor were randomly assigned to receive, in a double-blind fashion, one of five treatments. These were 25 mg meperidine, 12.5 mg bupivacaine, 25 mg meperidine plus 12.5 mg bupivacaine, 25 mg bupivacaine, and 37.5 mg bupivacaine. Efficacy of analgesia and side effects were assessed before and after each dose. Leg strength was measured with a force meter and blood flow to each foot with a blood perfusion monitor. The neurobehavioral state of the newborn was assessed by a pediatrician who was blind to treatment using a neurologic and adaptive capacity scoring system. RESULTS: Thirty-seven women did not achieve satisfactory analgesia after the first dose of test medication; these predominantly were those who received 25 mg meperidine (n = 12) or 12.5 mg bupivacaine (n = 11). Nausea decreased after the initial dose with all treatments (p less than 0.01), whereas shivering increased in patients receiving bupivacaine (p less than 0.01). There was a reduction in leg strength and an increase in blood flow associated with the two higher bupivacaine treatments (p less than 0.01), and with both parameters the dependent limb was most affected. Overall patient satisfaction was greatest in the group receiving meperidine plus bupivacaine. Neonatal neurologic and adaptive capacity scores did not differ significantly among the treatment groups. CONCLUSION: The low-dose combination of meperidine and bupivacaine used in this trial proved a satisfactory preparation for epidural administration during the early stages of labor. PMID- 1599889 TI - Differential epidural block. AB - BACKGROUND AND OBJECTIVES: Loss of sensation to pinprick and cold are commonly used to test the extent of epidural anesthesia. To see what difference exists between the level of epidural block determined by various sensory modalities, we performed this study in ten volunteers using epidural anesthesia with plain 3% chloroprocaine hydrochloride. METHODS: Four injections of chloroprocaine were made via an epidural catheter inserted at L2-3 with increasing larger volumes. Sensory modalities tested were (1) absence of sensation when tested by pinprick (anesthesia), (2) loss of a sharp sensation compared to an unblocked dermatome when tested by pinprick (analgesia), and (3) loss of cold sensation when tested with an alcohol swab compared to an unblocked dermatome. RESULTS: At 20 minutes after each injection the level of anesthesia was found to be most caudad and the level of analgesia most cephalad. The zone of differential block was greater than four dermatomes at the highest level of block tested. The level of loss of cold sensation was found between the other two levels. Differences between the levels of analgesia and cold sensation tended to be greater with more extensive block. Differences between levels of anesthesia and cold sensation did not significantly change as the extent of epidural anesthesia was increased. CONCLUSIONS: This study establishes the existence of a differential epidural anesthesia during high thoracic block with chloroprocaine and suggests that the intensity of block diminishes as distance from site of injection increases. PMID- 1599890 TI - Continuous epidural methadone for the management of postoperative pain after lower abdominal surgery. AB - BACKGROUND AND OBJECTIVES: The efficacy of methadone administered by continuous epidural infusion for 24 hours for the management of postoperative pain has been reported. The pharmacokinetic characteristics of methadone predict that significant accumulation would occur if infusions were continued for longer than 24 hours and that this accumulation could result in serum concentrations above the threshold associated with systemic analgesia. METHODS: We tested this hypothesis by measuring serum methadone concentrations, pain scores, and side effects in 18 patients receiving continuous epidural infusions of methadone for the relief of postoperative pain after lower abdominal surgery over 3 days. RESULTS: Twelve of 18 patients completed the study. Persistent inadequate analgesia required a change in the infusion mixture in 5 of these patients by the second postoperative day. The sixth patient suffered a fatal pulmonary embolus (judged to be unrelated to the study) on the morning of the first postoperative day. Methadone concentrations increased significantly from 20 +/- 18 ng/ml (median +/- quartile) on postoperative Day 1 to 70 +/- 47 ng/ml on Day 3. Pain relief scores steadily increased from 50 +/- 5 at 2 hours postoperatively to 83 +/- 5 by Day 3. The only side effects noted in the present study were nausea and sedation. CONCLUSION: The accumulation of serum concentrations reported here argue that the risks of thoracic epidural placement may outweigh the potential benefits when methadone is administered alone by continuous infusion for longer than 24 hours. PMID- 1599891 TI - Sprotte needle for obstetric anesthesia: decreased incidence of post dural puncture headache. AB - BACKGROUND AND OBJECTIVES: Reports have emphasized the importance of spinal needle tip configuration in the development of post dural puncture headache (PDPH). METHODS: Charts from 366 consecutive obstetric patients receiving spinal anesthesia for labor, cesarean delivery, postpartum surgical procedures, or postpartum tubal ligations were reviewed retrospectively for evidence of PDPH in the five days after dural puncture. Spinal anesthesia was administered to these patients using 25-gauge Quincke (n = 74), 26-gauge Quincke (n = 160), or 24-gauge Sprotte (n = 132) spinal needles. RESULTS: The groups were well matched demographically. The incidence of PDPH in the three groups was 9%, 8%, and 1.5%, respectively. Half of the patients developing PDPH in each group were treated with an epidural blood patch. CONCLUSIONS: Our data indicate that the Sprotte spinal needle, with its non-cutting tip, results in a significantly lower (p less than 0.05) incidence of PDPH than Quincke cutting-tip needles of smaller gauge. PMID- 1599892 TI - Effect of subarachnoid morphine on the incidence of spinal headache. AB - BACKGROUND AND OBJECTIVES: The addition of fentanyl to hyperbaric local anesthetics has been shown to reduce the incidence of post dural puncture headache in the obstetric patient. This study was undertaken to evaluate the effects of subarachnoid morphine on the incidence of headache. METHODS: Eighty two healthy patients undergoing cesarean delivery with spinal anesthesia were studied. All patients were hydrated with 1500 ml lactated Ringer's solution. Patients were randomly assigned to receive, in a double-blind fashion, 0.2 mg of either morphine (Group 1, n = 40) or saline (Group 2, n = 42) in 0.2 ml volume mixed with 0.75% bupivacaine in 8.25% dextrose plus 0.2 ml 1:1000 epinephrine. Spinal anesthesia was induced using a 25-gauge spinal needle at L3-4 interspace with the bevel, in most cases, parallel to the dural fibers. Patients were followed for three days to evaluate the incidence and severity of headache using a four-category rank scale (none, mild, moderate, severe). Data were analyzed for statistical significance using Student's t-test or chi-square test as appropriate. A p value less than 0.05 was considered significant. Results. The incidence of post dural puncture headache did not differ significantly between groups. Eight patients in Group 1 versus nine patients in Group 2 developed headache (p greater than 0.05). Similarly, the use of blood patch or intravenous caffeine sodium benzoate to treat the headache did not differ significantly between groups. CONCLUSION: It is concluded from our study that subarachnoid morphine did not decrease the incidence of post dural puncture headache in the obstetric patient. PMID- 1599893 TI - Sites of action of subarachnoid lidocaine and tetracaine: observations with evoked potential monitoring during spinal cord stimulator implantation. AB - BACKGROUND: The precise sites of action of local anesthetics on the spinal cord remain speculative. Monitoring spinal cord conduction during spinal anesthesia may provide a more precise localization of anesthetic action. METHODS: Fifteen patients admitted for elective surgical implantation of spinal cord stimulators for treatment of chronic pain participated in the study. Lidocaine (mean dose, 90 mg) was used in 14 patients; one patient received 7.5 mg tetracaine. To assess spinal cord conduction, paresthesias elicited by spinal cord stimulation were monitored during onset and maintenance of spinal anesthesia. In eight patients, evoked potential monitoring was used to further assess cord conduction. RESULTS: Despite complete motor block of the lower extremities and sensory levels to upper thoracic dermatomes (T1-8), all patients felt trial stimulator-induced paresthesias during spinal anesthesia. In addition, cortical evoked potentials from cord stimulation were maintained during spinal anesthesia. However, attenuation of cortical evoked potential amplitudes and paresthesias occurred, which were restored by increasing stimulus intensity. In contrast, even at maximum stimulus intensity, paresthesias and somatosensory evoked potentials from tibial nerve stimulation were abolished during spinal anesthesia. CONCLUSION: Based on these observations, the predominant site of action of subarachnoid lidocaine and tetracaine appeared to be at spinal rootlets, although partial block of afferent cord conduction also occurred. PMID- 1599894 TI - Ultrasonic guidance of lumbar sympathetic and celiac plexus block: a new technique. AB - BACKGROUND AND OBJECTIVES: Lumbar sympathetic and celiac plexus block are widely used to treat chronic pain of diverse etiologies. To avoid complications and confirm the correct position of the needle, fluoroscopy and computed tomography have been used to follow the procedure visually. Our objective was to examine whether ultrasonography could be used instead of these techniques. METHODS: Forty eight neurolytic sympathectomies were performed using ultrasonographic guidance. The results were evaluated clinically and by color-doppler technique as applicable. RESULTS: This new technique was shown to provide excellent results in ensuring the safe passage of the needle and documenting the correct spread of neurolytic agent (phenol-glycerol). The correct position of the needle was achieved on the first attempt in all cases. CONCLUSIONS: The benefits of this technique are that it is inexpensive, there is no radiation, and the anatomy involved can be thoroughly examined before and after the procedure. Phenolglycerol may be the best choice as the neurolytic agent because it provides excellent contrast. PMID- 1599895 TI - Venous levels of lidocaine and bupivacaine after midtarsal ankle block. AB - BACKGROUND: No data are available on blood levels of local anesthetics after ankle block. METHODS: Eighteen patients received 13 ml 2% lidocaine and ten received 30 ml 0.75% bupivacaine for unilateral or bilateral midtarsal ankle blocks, respectively. Blood levels were drawn at 15, 30, 45, 60, 90, 120, and 180 minutes after injections. All patients had forefoot surgery with elastic bandages (Esmarch) applied as a tourniquet immediately above the ankle intraoperatively. RESULTS: The mean peak level of lidocaine was 1.1 micrograms/ml, and of bupivacaine, 0.5 micrograms/ml. The mean duration of analgesia was 17 hours with 0.75% bupivacaine. Duration could not be assessed in the lidocaine group because these were ambulatory patients. CONCLUSION: The low peak level of local anesthesia and the prolonged analgesia confirmed the safety and efficacy of midtarsal ankle block for forefoot surgery and suggest that bupivacaine may be the local anesthetic agent of choice. PMID- 1599896 TI - Trigeminal nerve block as a complication of epidural anesthesia. AB - BACKGROUND AND METHODS: A healthy pregnant woman underwent labor under successful epidural analgesia with a total drug mass of 100 mg plain bupivacaine plus 100 micrograms fentanyl in three doses given over 150 minutes. RESULTS: Ninety minutes after the last dose, she developed signs and symptoms of a left trigeminal nerve block along with an ipsilateral Horner's syndrome. The cutaneous anesthesia level reached C6 on the left and T6 on the right side. Neurologic symptoms disappeared four hours later. CONCLUSION: An excessive upward epidural extension of bupivacaine block, reaching the trigeminal spinal nucleus and/or tract in the cervical spinal cord, is postulated. PMID- 1599897 TI - Bilateral subdural hematomas after dural puncture: delayed diagnosis after false negative computed tomography scan without contrast. AB - BACKGROUND. Dural puncture secondary to spinal anesthesia or unintentional dural puncture during attempted epidural anesthesia can lead to headaches complicated by bilateral subdural hematomas. Routine computed tomography scan may not elucidate bilateral subdural hematomas in the isodense phase. CONCLUSION. Computed tomography scans with contrast media or magnetic resonance imaging may be necessary to diagnose bilateral subdural hematomas. PMID- 1599898 TI - Post dural puncture headache with a Sprotte needle. PMID- 1599899 TI - Identification of the epidural space by the gravity flow technique. PMID- 1599900 TI - Production of epidermal sheets in a serum free culture system: a further appraisal of the role of extracellular calcium. AB - Rhenwald and Green's technique is currently the standard method for growing stratifying epidermal cell cultures. The serum free system developed in Ham's laboratory (MCDB 153) was designed to grow keratinocyte monolayers in clonogenic conditions. Our aim was to optimize conditions in serum-free MCDB 153 for culturing epidermal sheets from adult normal skin, and to assess the effect of extracellular calcium and temperature on proliferation and differentiation of cultured keratinocytes. Sixteen strains derived from plastic surgery specimens (mean age of donors 37 years; range 5-89) were used. Primary cultures were seeded at an optimal density of 8 x 10(4) cells/cm2 in primary cultures and 10(4) cells/cm2 in secondary cultures in complete medium including EGF, insulin, hydrocortisone and bovine pituitary extract, supplemented with isoleucine, tyrosine, methionine, phenylalanine, tryptophane and histidine. Amino acid (AA) supplementation allows a 5.8-fold increase in cell counts at confluency and monolayers with densely packed cells are obtained. In AA supplemented cultures, confluency is obtained in 16 +/- 3 days in primary cultures and in 13 +/- 0.5 days at first passages. Switches to 1.1 mM calcium at first or second passages resulted in a significant increase in cell counts (P less than 0.001), when compared with AA supplemented low calcium cultures. Low temperature/low calcium cultures resulted in a 50% decrease in cell counts. Low temperature/high calcium cultures gave similar cell counts as the 37 degrees C controls. AA and calcium supplemented cultures were evaluated for differentiation markers: involucrin expression was increased, keratins 5, 6, 14, 17 were expressed, and the sheets were 6-10 layers thick by electron microscopy, with keratohyalin granules and cornified envelopes appearing at layers 3-6 (from basal layer). Dispase treatment allowed an easy detachment of these sheets. These results show that the culture medium MCDB 153 can be adapted without serum supplementation to batch culture of human adult keratinocytes to produce epidermal sheets suitable for grafting. They also indicate that extracellular calcium in physiological range of concentration is not a sufficient signal for growth arrest when other growth conditions are optimized. PMID- 1599901 TI - Affinity of SSB/La nuclear antigen to small nuclear ribonucleic acids. AB - Anti-SSB/La antibody is one kind of antinuclear antibody and is found predominantly in patients with Sjogren's syndrome and systemic lupus erythematosus. SSB/La antigen is present in the nucleus as ribonucleoprotein in particle form and is composed of peptide and RNAs. SSB/La antigen can be partially purified through several sequential procedures including salt fractionation and ion exchange chromatography. SSB/La antigen is capable of binding to 4 RNAs from uninfected KB cells and 6 RNAs from Epstein-Barr virus transformed WiL2 cells. These RNAs can bind to SSB/La peptide in vitro and form ribonucleoprotein complexes which could be reprecipitated by anti-SSB/La antibody. SSB/La associated RNAs are labile and subjected to degradation easily. Anti-SSB/La antibody may be a useful probe to investigate the potential role of Epstein-Barr virus involvement in cutaneous pathology. PMID- 1599902 TI - House dust mite (HDM) antigen in naturally occurring lesions of atopic dermatitis (AD): the relationship between HDM antigen in the skin and HDM antigen-specific IgE antibody. AB - To elucidate the etiological role of house dust mite (HDM) antigen in the pathogenesis of atopic dermatitis (AD), we conducted immunohistochemical studies on the localization of HDM antigen in naturally occurring lesions of AD. HDM antigens were found in the epidermis and dermis in 19 of 38 cases. All of the 19 patients had HDM antigen-specific IgE antibody, but HDM antigen was not detected in the lesions of patients without HDM antigen-specific IgE or in control skin specimens. Most HDM antigens were located on Langerhans cells (LCs) or near helper T cells. Our findings suggest that HDM antigen is the causative factor in the development of eczematous lesions of AD, and thus we hypothesized that IgE mediated allergic contact sensitivity to HDM antigen plays an important role in the pathogenesis of AD. PMID- 1599903 TI - In situ [3H]thymidine labelling of human hair papilla: an in vitro autoradiographic study. AB - The labelling index (LI) and the location of labelled cells in the papilla of human anagen scalp hair have been studied after in vitro [3H]thymidine (3H-TdR) pulse labelling. Forty-three anagen stage VI papillae from 2 individuals (both females, 25 and 55 years) obtained by micropreparation from deep scalp biopsies were analysed. Labelled cells were found only paraaxially in the basal third of the papilla, i.e. below Auber's line. The 3H-TdR-LI of the papilla cells (0.13 and 0.16%) is about 200-times lower than that of the hair matrix cells below the line of Auber (25.5 and 29.5%). The biological significance of this low proliferation rate in the anagen stage VI hair papilla of healthy human should be defined. PMID- 1599904 TI - The effects of non-interval PUVA treatment on Langerhans cells and contact hypersensitivity. AB - Although application of topical psoralen followed immediately by ultraviolet-A irradiation (non-interval PUVA) was reported to be effective in the treatment of psoriasis, its precise mechanisms of action have not yet been explored. Since regular topical PUVA therapy, consisting of the topical application of psoralen followed by UVA exposure 1-2 h later, can change the number and morphology of Langerhans cells (LCs) and inhibit contact hypersensitivity (CHS), we investigated whether these same effects may be induced by non-interval PUVA. Our results showed that no differences exist between these two types of PUVA treatment. Non-interval PUVA treatments of 3 J/cm2 produced no erythematous reactions and resulted in changes in the number and morphology of LCs. The non interval regimen also inhibited CHS to dinitrofluorobenzene applied to the treated skin by inducing the suppressor lymphocytes. These results suggest that there might be a link between the observed changes of the LCs and the effectiveness of non-interval PUVA therapy in the treatment of psoriasis, through a mechanism other than the inhibition of DNA synthesis of psoriatic keratinocytes. PMID- 1599905 TI - Prevention of galactose cataract by pyruvate. AB - The effect of pyruvate on the progress of galactose cataract has been studied. Pyruvate was administered topically in the form of eye drops. Such treatment was found to delay the onset of the cataractous changes. Cataract formation was studied by visual inspection with pen light, as well as with slit lamp biomicroscopy in the intact animal. The delay in the formation of cataract was associated with the preservation of the levels of lens ATP, soluble proteins and the decreased accumulation of galactitol. In vitro organ culture experiments yielded similar results. PMID- 1599906 TI - Lens opacification and H2O2 elevation induced by a tumor promoter. AB - Incubation of whole bovine lens with 10(-7) M 12-O-tetradecanoylphorbol-13 acetate (TPA) led to the lens opacity within 24 h. The hydrogen peroxide (H2O2) concentration in the whole lens was elevated 4 fold after treatment with either 10(-7) M TPA or 2.5 mM glucose/20 microM glucose oxidase. The lens opacification and H2O2 elevation were TPA dose-dependent. Preincubation of the lens with anti tumor promoting agents EGCG (epigallocatechin gallate) or Sarp A (sarcophytol A) stopped the TPA-mediated opacification process and suppressed H2O2 elevation. PMID- 1599907 TI - Elemental distribution in frozen-hydrated mouse lenses with hereditary cataract. AB - Nakano mice (nct/nct) and its congenic strain (Balb/c-nct/nct) develop different types of cataract: the former develop intense nuclear cataract but the latter develop milder opacity at the cortical region of lenses more later in life. The present study was undertaken to compare the elemental compositions at the localized region of these lenses in order to examine the possible role of ions in the opacification of the hereditary cataracts. Eight lenses from Nakano mice (age: 39-40 days) and ten lenses from congenic mice (age: 73 days) were prepared for the X-ray analysis with a high energy ion microprobe at a resolution of 50 microns. The age of mice was two weeks after 50% cataract formation for the respective strain. The maps of the concentrations of S, Cl, K and Ca in the central planes of the frozen-hydrated lenses were obtained. In all of the congenic lenses analyzed, the normal elemental composition, low Cl and Ca, and high K, was retained only in the narrow anterial and equatorial peripheral region and the other region underwent a K loss with a gain of Cl and Ca. In the Nakano lenses, the altered elemental composition was localized in central and in posterial cortical regions. There was no distinct difference in the concentration levels of Cl, K and Ca in the central region of the lenses between the two strains. The level of S was lower in Nakano lenses. High calcium containing spots were detected in low K regions of some of the lenses examined. PMID- 1599908 TI - The effects of intraocular gases on rabbit blood-retinal barrier permeability. AB - The effects of intravitreal expansile gases, sulfur hexafluoride and octafluoropropane, as well as air and needle insertion alone were assessed by iris fluorescein angiography and blood-retinal barrier permeability determination. Iris angiography, at 3 days after injection, indicated no differences between experimental and paired control eyes. Vitreous fluorophotometry on day 1, day 4 and day 7 after gas or sham injection also showed no differences between paired control and experimental eyes regardless of which experimental condition was employed. The results indicate that these gases are non-toxic to the blood-retinal barrier over a 7 day time course. PMID- 1599910 TI - Flow cytometric analysis on perforin induction in peripheral blood mononuclear cells with interleukin-2 or OK-432. AB - Perforin is a protein present in the cytoplasmic granules of killer cells and is considered to be an important effector molecule. We assessed the perforin appearance via flow cytometry in human peripheral blood mononuclear cells stimulated in vitro for 3 days by recombinant interleukin-2 (rIL-2) or OK-432, a biological response modifier. The relationship between the lymphocyte subsets and perforin was investigated via two-color assay. CD4-positive cells had almost no perforin, and most of the CD16-positive cells did. Regarding the relationship with CD8, some of the bright positive cells (which were likely T cells) and most of the dull positive cells (likely NK cells) had perforin. Mean fluorescence was greatest in perforin-positive cells incubated with rIL-2, less in cells incubated with OK-432, and minimal in cells incubated in a medium without additives. Immunohistochemical staining with antiperforin antibody revealed that blast transformed and enlarge cells were stained positively and that the intensity of staining of each cell alone was enhanced in cells incubated with OK-432 or rIL-2. If the fluorescence intensity of perforin-positive cells correlates with the amount of perforin in those cells, then the appearance of perforin was enhanced with OK-432, more enhanced with rIL-2, and consistent for cytotoxicity against K562 and Daudi cells. IL-2 was induced by OK-432, suggesting that the indirect effect of this IL-2 may play a role in OK-432-perforin induction. The results suggest that perforin may be an effector molecule in killer cells induced by rIL 2 or OK-432. PMID- 1599909 TI - T-cell retargeting using bispecific monoclonal antibodies in a rat colon carcinoma model. I. Significant bispecific lysis of syngeneic colon carcinoma CC531 is critically dependent on prolonged preactivation of effector T lymphocytes by immobilized anti-T-cell receptor antibody. AB - In order to develop a rat model that reflects human weakly or nonimmunogenic tumor-host relationships and allows investigation of T-cell retargeting with bispecific monoclonal antibodies in vivo, we prepared several mixed hybridomas. One fusion partner was the anti-rat-T-cell receptor (TCR)-framework hybridoma R73 and the others were hybridomas producing antibodies against CC531, a Wag rat colon carcinoma. Stimulation of Wag rat spleen cells with immobilized R73 mAb and rIL-2 yielded predominantly CD8 positive effector T-lymphocytes, which lysed control P815 target cells efficiently in R73-mediated reverse antibody-dependent cellular cytotoxicity (ADCC). The capacity of these effectors to cause significant hybrid antibody-mediated lysis of CC531 emerged several days later, was critically dependent on prolonged stimulation with immobilized R73, and was associated with increased N-alfa-benzyloxycarbonyl-L-lysine thiobenzyl esterase content. PMID- 1599911 TI - Gamma-interferon enhancement of carcinoembryonic antigen expression in human colon carcinoma xenografts. AB - Athymic nu/nu mice bearing a subcutaneous human colon cancer xenograft (WiDr, low CEA expression) were treated with gamma-interferon (gamma IFN) at varying doses, frequencies, and periods of duration. CEA content (micrograms/g) and uptake of radiolabeled anti-CEA monoclonal antibody (MAB) (percent injected dose per gram, % ID/g) were measured at 48 h following administration of the MAB, The optimal enhancement of tumor CEA content and tumor localization of [111In] anti-CEA monoclonal antibody (MAB) was seen at gamma IFN doses of 100,000 U i.p. every 8 h for 4 days (4.7 micrograms/g; 29% ID/g) compared to control animals (0.9 micrograms/g; 10% ID/g). The effects of gamma IFN on CEA content and MAB localization were less pronounced when administered (a) at lower doses: 5,000 to 50,000 U i.p. every 8 h, (b) at varying frequencies: 300,000 U/day delivered in divided doses every 4 or 24 h, or (c) for varying periods: 2 or 6 days of therapy. In each case, the biologic effects on tumor CEA content and uptake of [111In]MAB correlated closely with the serum gamma IFN level. Therefore, we conclude that enhancement of in vivo CEA expression by gamma IFN may have clinical relevance for tumor imaging and therapy using radiolabeled monoclonal antibodies. PMID- 1599912 TI - Idiotype network responses to murine immunoglobulin G3 anti-carbohydrate antibodies. AB - Two murine monoclonal antibodies, 8A6 and 8C2, were generated against the carbohydrate moiety of tumor-associated disialoganglioside. Both of the antibodies were of the immunoglobulin G3 (IgG3), K isotype subclass. One of these antibodies (8A6) was used as a network immunogen for the generation of anti idiotype antibodies. Two AB2 anti-idiotype antibodies were identified. One AB2 (12E5) was subsequently shown to recognize a linear epitope of the 8A6 kappa light chain. The second AB2 (9H8), recognizes a conformational epitope which is dependent on the maintenance of the tertiary structure of the idiotype. Both anti idiotypes were injected into (syngeneic) mice and (xenogeneic) rabbits to evaluate their effectiveness as "network" antigens in promoting AB3 and anti carbohydrate AB1' responses. AB3 populations from both syngeneic and xenogeneic hosts were found to be idiotype-specific, yet were unable to produce a measurable subpopulation of anti-tumor (AB1'). These studies suggest that IgG3 isotypes may not be suitable idiotype templates for the mimicry of carbohydrate epitopes. PMID- 1599913 TI - Immunological evaluation of pediatric cancer patients receiving recombinant interleukin-2 in a phase I trial. AB - Immunological evaluations were performed on 14 pediatric cancer patients who received human recombinant interleukin-2 (rIL-2) as a bolus intravenous infusion every 8 h for 5 consecutive days in a phase I trial. Three-to-four patients were treated at dose levels of 10, 30, 60, and 100 x 10(3) Cetus U/kg. Six of the patients had stage D neuroblastoma; the remainder had other solid tumors or leukemias. Infusion of rIL-2 was associated with a rapid margination of IL-2 responsive cells followed by demargination and heightened proliferative and cytotoxic activity after therapy was completed. The predominant phenotypic change in circulating peripheral blood mononuclear cells (PBMC) was an increase in CD2 expression by CD56+ natural killer (NK) cells. Appearance of CD2+ CD56+ cells in the circulation correlated with increased lymphokine-activated killer (LAK) cell activity as defined by the ability to kill NK-resistant Daudi tumor cells in vitro. Sustained LAK activity appeared to be dependent on the bioavailability of rIL-2 in vivo as well as in vitro. After rIL-2 therapy, PBMC that were highly responsive to rIL-2 (activated and "poised" LAK cells) persisted for at least 72 h. In the patients tested, increased lysis of autologous and/or allogeneic, histologically similar tumor cell lines was also observed after therapy. The immunoenhancing effects of rIL-2 occurred even at the lower doses used in this study. However, an objective tumor response was not observed in any of the patients. PMID- 1599914 TI - Phase I study of low-dose cyclophosphamide and recombinant interleukin-2 for the treatment of advanced cancer. AB - We conducted a phase I study of low-dose cyclophosphamide and recombinant interleukin-2 (rIL-2) in 66 patients with advanced cancer resistant to standard therapy. All patients were evaluable for toxicity and 46 patients were evaluable for antitumor response. Patients evaluable for antitumor response included 23 with malignant melanoma, 10 with renal cell carcinoma, 4 with colon cancer, and 9 with various other solid tumors. All patients received i.v. cyclophosphamide (350 mg/m2) on day 1 followed by rIL-2 via 15 min i.v. infusion on days 4-8 and 11-15. The doses of rIL-2 ranged from 6.0 to 36.0 x 10(6) IU/m2. Each treatment cycle consisted of 21 days and a total of 113 cycles was administered. The number of treatment cycles administered per patient ranged from 1 to 8. The dose-limiting toxicities associated with rIL-2 included altered mental status, arthralgias, diarrhea, fatigue, fever, hypotension, nausea/vomiting, and peripheral edema. Twelve patients (18%) were removed from the study secondary to toxicity. Among the evaluable patients, 2 (4%) (malignant melanoma, renal cell carcinoma) developed a partial remission, 13 (29%) maintained stable disease, and 31 (67%) developed progressive disease. We conclude that the combination of low-dose cyclophosphamide and rIL-2 is tolerable in most patients but our data do not suggest an improved response rate for the combination vs. rIL-2 alone. PMID- 1599915 TI - Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen. AB - In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1599916 TI - Rhodopsin: structure, function, and genetics. PMID- 1599917 TI - RNA tetraloops as minimalist substrates for aminoacylation. AB - Previous work established that seven-base-pair hairpin microhelices with sequences based on the acceptor stems of alanine, glycine, methionine, and histidine tRNAs can be aminoacylated specifically with their cognate amino acids. To obtain "minimalist" substrates with fewer base pairs, we took advantage of the high thermodynamic stability of RNA tetraloop motifs that are found in ribosomal RNAs. We show here that rationally designed RNA tetraloops with as few as four base pairs are substrates for aminoacylation. Major nucleotide determinants for recognition by the class II synthetases were incorporated into each of the respective tetraloop substrates, resulting in specific aminoacylation by the alanine, glycine, and histidine tRNA synthetases. An analysis of the kinetics of aminoacylation shows that, for the alanine system, the majority of the transition state stabilization provided by the synthetase-tRNA interaction is reproduced by the interaction of the synthetase with nucleotides in its minimalist tetraloop substrate. In an extension of this work, we also observed specific aminoacylation with the class I methionine tRNA synthetase of RNA tetraloops based on sequences in the acceptor stem of methionine tRNA. Thus, the results demonstrate four different examples where specific aminoacylation is directed by sequences/structures contained in less than half of a turn of an RNA helix. PMID- 1599918 TI - Energetics of folding subtilisin BPN'. AB - Subtilisin is an unusual example of a monomeric protein with a substantial kinetic barrier to folding and unfolding. Here we document for the first time the in vitro folding of the mature form of subtilisin. Subtilisin was modified by site-directed mutagenesis to be proteolytically inactive, allowing the impediments to folding to be systematically examined. First, the thermodynamics and kinetics of calcium binding to the high-affinity calcium A-site have been measured by microcalorimetry and fluorescence spectroscopy. Binding is an enthalpically driven process with an association constant (Ka) equal to 7 x 10(6) M-1. Furthermore, the kinetic barrier to calcium removal from the A-site (23 kcal/mol) is substantially larger than the standard free energy of binding (9.3 kcal/mol). The kinetics of calcium dissociation from subtilisin (e.g., in excess EDTA) are accordingly very slow (t1/2 = 1.3 h at 25 degrees C). Second, to measure the kinetics of subtilisin folding independent of calcium binding, the high-affinity calcium binding site was deleted from the protein. At low ionic strength (I = 0.01) refolding of this mutant requires several days. The folding rate is accelerated almost 100-fold by a 10-fold increase in ionic strength, indicating that part of the free energy of activation may be electrostatic. At relatively high ionic strength (I = 0.5) refolding of the mutant subtilisin is complete in less than 1 h at 25 degrees C. We suggest that part of the electrostatic contribution to the activation free energy for folding subtilisin is related to the highly charged region of the protein comprising the weak ion binding site (site B).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599919 TI - Simulation of the solution structure of the H-ras p21-GTP complex. AB - An unconstrained simulation of the GTP-bound form of the H-ras protein p21 is performed in an aqueous environment with charge-neutralizing counterions. The simulation is compared to the 1.35-A structure of Pai et al. [(1990) EMBO J. 9, 2351] and a proposed alternate structure, in which the loop at residues 60-65 is modeled into a form which may activate a water molecule for the GTP hydrolysis. The simulation suggests that some protein intermolecular H-bond contacts which are present in the crystal structure are lost in the solvation process and this loss may lead to localized refolding of the molecule. For instance, we find that the gamma-phosphate of the GTP has somewhat weaker contact with the protein in the simulation structure. The antiparallel beta-sheet (residues 38-57) partially melts. The 60-65 loop, which is hypervariable in the X-ray study, is initially relatively distant from the gamma-phosphate region. However, this loop moves so as to sample the space around the gamma-phosphate. For a significant fraction of the simulation time, forms similar to the alternate structure are observed, and a water molecule is localized near the hydrolytic site. The molecular dynamics simulations of p21-GTP in solution support a postulated hydrolysis mechanism for the biological inactivation of the nucleotide complex based on crystallographic data. PMID- 1599920 TI - Crystal structure of an electron-transfer complex between methylamine dehydrogenase and amicyanin. AB - The crystal structure of the complex between the quinoprotein methylamine dehydrogenase (MADH) and the type I blue copper protein amicyanin, both from Paracoccus denitrificans, has been determined at 2.5-A resolution using molecular replacement. The search model was MADH from Thiobacillus versutus. The amicyanin could be located in an averaged electron density difference map and the model improved by refinement and model building procedures. Nine beta-strands are observed within the amicyanin molecule. The copper atom is located between three antiparallel strands and is about 2.5 A below the protein surface. The major intermolecular interactions occur between amicyanin and the light subunit of MADH where the interface is largely hydrophobic. The copper atom of amicyanin and the redox cofactor of MADH are about 9.4 A apart. One of the copper ligands, His 95, lies between the two redox centers and may facilitate electron transfer between them. PMID- 1599921 TI - Structural consequences of the natural substitution, E9K, on reactive-site hydrolyzed squash (Cucurbita maxima) trypsin inhibitor (CMTI), as studied by two dimensional NMR. AB - Sequence-specific hydrogen-1 NMR assignments were made to all of the 29 amino acid residues of reactive-site-hydrolyzed Cucurbita maxima trypsin inhibitor I (CMTI-I*) by the application of two-dimensional NMR (2D NMR) techniques, and its secondary structural elements (two tight turns, a 3(10)-helix, and a triple stranded beta-sheet) were identified on the basis of short-range NOESY cross peaks and deuterium-exchange kinetics. These secondary structural elements are present in the intact inhibitor [Holak, T. A., Gondol, D., Otlewski, J., & Wilusz, T. (1989) J. Mol. Biol. 210, 635-648] and are unaffected by the hydrolysis of the reactive-site peptide bond between Arg5 and Ile6, in accordance with the earlier conclusion reached for CMTI-III* [Krishnamoorthi, R., Gong, Y. X., Lin, C. S., & VanderVelde, D. (1992) Biochemistry 31, 898-904]. Chemical shifts of backbone hydrogen atoms, peptide NH's, and C alpha H's, of CMTI-I* were compared with those of the intact inhibitor, CMTI-I, and of the reactive-site hydrolyzed, natural, E9K variant, CMTI-III*. Cleavage of the Arg5-Ile6 peptide bond resulted in changes of chemical shifts of most of the backbone atoms of CMTI I, in agreement with the earlier results obtained for CMTI-III. Comparison of chemical shifts of backbone hydrogen atoms of CMTI-I* and CMTI-III* revealed no changes, except for residues Glu9 and His25. However, the intact forms of the same two proteins, CMTI-I and CMTI-III, showed small but significant perturbations of chemical shifts of residues that made up the secondary structural elements of the inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599922 TI - Substrate specificities of tissue kallikrein and T-kininogenase: their possible role in kininogen processing. AB - The present studies demonstrate the importance of subsite interactions in determining the cleavage specificities of kallikrein gene family proteinases. The effect of substrate amino acid residues in positions P3-P'3 on the catalytic efficiency of tissue kallikreins (rat, pig, and horse) and T-kininogenase was studied using peptidyl-pNA and intramolecularly quenched fluorogenic peptides as substrates. Kinetic analyses show the different effects of D-amino acid residues at P3, Pro at P'2, and Arg at either P'1 or P'3 on the hydrolysis of substrates by tissue kallikreins from rat and from horse or pig. T-Kininogenase was shown to differ from tissue kallikrein in its interactions at subsites S2, S'1, and S'2. As a result of these differences, Abz-FRSR-EDDnp with Arg at P'2 is a good substrate for tissue kallikreins from horse, pig, and rat but not for T kininogenase. Abz-FRRP-EDDnp and Abz-FRAPR-EDDnp with Pro at P'2 (rat high molecular weight kininogen sequence) are susceptible to rat tissue kallikrein but not to tissue kallikreins from horse and pig. Arg at P'3 increased the susceptibility of the Arg-Ala bond to rat tissue kallikrein. These data explain the release of bradykinin by rat tissue kallikrein and of kallidin by tissue kallikreins from other animal species. Abz-FRLV-EDDnp and Abz-FRLVR-EDDnp (T kininogen sequence) are good substrates for T-kininogenase but not for tissue kallikrein. Arg at the leaving group (at either P'1, P'2, or P'3) lowers the Km values of T-kininogenase while Val at P'2 increases its kcat values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599923 TI - Stereochemical and positional specificity of the lipase/acyltransferase produced by Aeromonas hydrophila. AB - Aeromonas species secrete a glycerophospholipid-cholesterol acyltransferase (GCAT) which shares many properties with mammalian plasma lecithin-cholesterol acetyltransferase (LCAT). We have studied the stereochemical and positional specificity of GCAT against a variety of lipid substrates using NMR spectroscopy as well as other assay methods. The results show that both the primary and secondary acyl ester bonds of L-phosphatidylcholine can be hydrolyzed but only the sn-2 fatty acid can be transferred to cholesterol. The enzyme has an absolute requirement for the L configuration at the sn-2 position of phosphatidylcholine. The secondary ester bond of D-phosphatidylcholine cannot be hydrolyzed, and this lipid is not a substrate for acyl transfer. In contrast to the phospholipases, but similar to LCAT, the enzyme does not interact stereochemically with the phosphorus of phosphatidylcholine. In fact, the phosphorus is not required for enzyme activity, as GCAT will also hydrolyze monolayers of diglyceride, although at much lower rates. PMID- 1599924 TI - Mechanism of inhibition of human leukocyte elastase by two cephalosporin derivatives. AB - The cephalosporin derivatives L 658758 [1-[[3-(acetoxymethyl)-7 alpha-methoxy-8 oxo-5-thia-1-azabicyclo [4.2.0]oct-2-en-2-yl]carbonyl]proline S,S-dioxide] and L 659286 [1-[[7 alpha-methoxy-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo- 1,2,4-triazin-3-yl)thio]methyl]-5-thia-1-aza-(6R)-bicyclo[4.2.0]-o ct-2-en-2 yl]carbonyl]pyrrolidine S,S-dioxide] are mechanism based inhibitors of human leukocyte elastase (HLE). The mechanism involves initial formation of a Michaelis complex followed by acylation of the active site serine. The group on the 3' methylene is liberated during the course of these reactions, followed by partitioning of an intermediate between hydrolysis to regenerate active enzyme and further modification to produce a stable HLE-inhibitor complex. The partition ratio of 2.0 obtained for the reaction with L 658758 approaches that of an optimal inhibitor. These compounds are functionally irreversible inhibitors as the recovery of activity after inactivation is slow. The half-lives at 37 degrees C of the L 658758 and L 659286 derived HLE-I complexes were 9 and 6.5 h, respectively. The complexes produced by both inhibitors are similar chemically since the thermodynamic parameters for activation to regenerate active enzyme are essentially identical. The free energy of activation for this process is dominated primarily by the enthalpy term. The stability of the final complexes likely arises from Michael addition on the active site histidine to the 3' methylene. PMID- 1599925 TI - Oxidation of phenolic arylglycerol beta-aryl ether lignin model compounds by manganese peroxidase from Phanerochaete chrysosporium: oxidative cleavage of an alpha-carbonyl model compound. AB - Manganese peroxidase (MnP) oxidized 1-(3,5-dimethoxy-4-hydroxyphenyl)-2-(4 (hydroxymethyl)-2-methoxyphenoxy) -1,3-dihydroxypropane (I) in the presence of MnII and H2O2 to yield 1-(3,5-dimethoxy-4-hydroxyphenyl)- 2-(4-(hydroxymethyl)-2 methoxyphenoxy)-1-oxo-3-hydroxypropane (II), 2,6-dimethoxy-1,4-benzoquinone (III), 2,6-dimethoxy-1,4-dihydroxybenzene (IV), 2-(4-(hydroxymethyl)-2 methoxyphenoxy)-3-hydroxypropanal (V), syringaldehyde (VI), vanillyl alcohol (VII), and vanillin (VIII). MnP oxidized II to yield 2,6-dimethoxy-1,4 benzoquinone (III), 2,6-dimethoxy-1,4-dihydroxybenzene (IV), vanillyl alcohol (VII), vanillin (VIII), syringic acid (IX), and 2-(4-(hydroxymethyl)-2 methoxyphenoxy)-3-hydroxypropanoic acid (X). A chemically prepared MnIII-malonate complex catalyzed the same reactions. Oxidation of I and II in H2(18)O under argon resulted in incorporation of one atom of 18O into the quinone III and into the hydroquinone IV. Incorporation of one atom of oxygen from H2(18)O into syringic acid (IX) and the phenoxypropanoic acid X was also observed in the oxidation of II. These results are explained by mechanisms involving the initial one-electron oxidation of I or II by enzyme-generated MnIII to produce a phenoxy radical. This intermediate is further oxidized by MnIII to a cyclohexadienyl cation. Loss of a proton, followed by rearrangement of the quinone methide intermediate, yields the C alpha-oxo dimer II as the major product from substrate I. Alternatively, cyclohexadienyl cations are attacked by water. Subsequent alkyl phenyl cleavage yields the hydroquinone IV and the phenoxypropanal V from I, and IV and the phenoxypropanoic acid X from II, respectively. The initial phenoxy radical also can undergo C alpha-C beta bond cleavage, yielding syringaldehyde (VI) and a C6-C2-ether radical from I and syringic acid (IX) and the same C6-C2 ether radical from II. The C6-C2-ether radical is scavenged by O2 or further oxidized by MnIII, subsequently leading to release of vanillyl alcohol (VII). VII and IV are oxidized to vanillin (VIII) and the quinone III, respectively. PMID- 1599926 TI - Minimum ribonucleotide requirement for catalysis by the RNA hammerhead domain. AB - Several mixed DNA/RNA and 2'-O-methylribonucleotide/RNA analogues derived from the "hammerhead" domain of RNA catalysis have been prepared to study the minimum ribonucleotide requirement for catalytic activity. Oligodeoxyribonucleotides containing from seven to as few as four ribonucleotides are active in cleaving a substrate RNA. Predominantly deoxyribonucleotide-containing analogues have kcat values 20-300 and kcat/KM values approximately 100-2000 times lower than those of all-RNA ribozyme. In the case of predominantly 2'-O-methyl analogues, at least five ribonucleotides are needed to assure catalytic activity. In addition, both predominantly deoxyribonucleotide and 2'-O-methyl oligomers are at least 3 orders of magnitude more stable than an all-RNA ribozyme in incubations with RNase A and a yeast extract. These results suggest that the ribophosphate backbone is not a strict requirement for ribozyme-type catalysis. The identification of the four required ribonucleotides in the hammerhead catalytic domain provides valuable information for the rational design of chemical species having ribonuclease activities. PMID- 1599927 TI - Design and synthesis of a helix heparin-binding peptide. AB - Elaboration of heparin-protein-binding interactions is necessary to understand how heparin modulates protein function. The heparin-binding domain of some proteins is postulated to be a helix structure which presents a surface of high positive charge density. Thus, a synthetic 19-residue peptide designed to be alpha-helical in character was synthesized, and its interaction with heparin was studied. The peptide was shown to be 75% helix by circular dichroism (CD) spectrometry in neutral pH buffer (at 2 degrees C); helicity increased to nearly 85% under high ionic strength conditions or to nearly 100% in 75% ethanol. Increasing the temperature of the solution caused a change in the spectral envelope consistent with a coil transition of the peptide. The midpoint of the transition (i.e., the temperature at which the helix content was determined to be 50%) was 25 degrees C, and the determined van't Hoff enthalpy change (delta HvH) was 3.2 kcal/mol of peptide. By CD, heparin increases the helix content of the peptide to 100% and increases the apparent thermal stability of the peptide by about 1 kcal/mol. The melting point for the helix/coil transition of the heparin peptide complex was 50 degrees C. The thermal coefficient of the transition (approximately 300 deg.cm2.dmol-1.degree C-1) was essentially the same for the peptide alone or the peptide-heparin complex. Dissociation of the complex under high ionic strength conditions was also observed in the CD experiment. Biological assays showed less heparin-binding activity than expected (micromolar KD values), but this was attributed to the absence of critical lysyl residues in the peptide.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599928 TI - Channel-forming activity of the perforin N-terminus and a putative alpha-helical region homologous with complement C9. AB - Cytolytic lymphocytes are endowed with a pore-forming protein called perforin. Recently, a cytolytic domain was located in the first 34 residues of the perforin N-terminus. It has been proposed that the first 19 residues are composed of a 3 domain structure including a putative amphipathic beta-sheet and that the 19 residues are sufficient for cytolytic activity. This model has now been tested by synthesizing peptides covering different portions of the N-terminus, and testing their ability to lyse lipid vesicles or increase the conductance of lipid bilayers or plasma membranes. It was found that the putative beta-sheet is indispensable for lytic activity and that the first 19 residues of the N-terminus are required for optimal lytic activity but that shorter peptides, containing only 16 residues, can form pores in lipid bilayers and cell membranes. A putative amphipathic alpha-helix from the central portion of perforin, homologous to complement C9, is nonlytic to lipid vesicles, but it can form pores in lipid bilayers. Taken together, these results support the model that the perforin N terminus is important in initial pore formation and that the putative alpha helical domain may be involved in subsequent perforin polymerization into large pores. PMID- 1599929 TI - Functional reconstitution of the nicotinic acetylcholine receptor by CHAPS dialysis depends on the concentrations of salt, lipid, and protein. AB - The detergent CHAPS was found to be the preferable surfactant for the efficient purification and reconstitution of the Torpedo californica nicotinic acetylcholine receptor (AChR). The main result is that the incorporation of the AChR proteins into lipid vesicles by CHAPS dialysis was strongly dependent on the salt and protein concentrations. As monitored by sucrose gradients, by electron microscopy, and by agonist-induced lithium ion flux, the best reconstitution yields were obtained in 0.5 M NaCl at a protein concentration of 0.5 g/L and in 0.84 M NaCl at 0.15 g/L protein. Electron micrographs of receptor molecules, which were incorporated into vesicles, showed single, nonaggregated dimer (M(r) = 580,000) and monomer (M(r) = 290,000) species. CHAPS dialysis at NaCl concentrations less than 0.5 M largely reduced the receptor incorporation concomitant with protein aggregation. Electron micrographs of these preparations revealed large protein sheets or ribbons not incorporated into vesicles. The analysis of static and dynamic light scattering demonstrated that the detergent solubilized AChR molecules aggregate at low lipid contents (less than or equal to 500 phospholipids/AChR dimer), independent of the salt concentration. AChR proteins eluted from an affinity column with a solution containing 8 mM CHAPS (but no added lipid) still contained 130 +/- 34 tightly bound phospholipids per dimer. The aggregates (about 10 dimers on the average) could be dissociated by readdition of lipid and, interestingly, also by increasing the CHAPS concentration up to 15 mM. This value is much higher than the CMC of CHAPS = 4.0 +/- 0.4 mM, which was determined by surface tension measurements. The data clearly suggest protein-micelle interactions in addition to the association of monomeric detergents with proteins. Furthermore, the concentration of the (free) monomeric CHAPS at the vesicle-micelle transformation in 0.5 M NaCl ([Dw]c = 3.65 mM) was higher than in 50 mM NaCl ([Dw]c = 2.8 mM). However, it is suggested that the main effect of high salt concentrations during the reconstitution process is an increase of the fusion (rate) of the ternary protein/lipid/CHAPS complexes with mixed micelles or with vesicular structures, similar to the salt-dependent fusion of vesicles. PMID- 1599930 TI - A vibrational analysis of the catalytically important C4-H bonds of NADH bound to lactate or malate dehydrogenase: ground-state effects. AB - We have measured the frequency of the carbon-hydrogen stretching mode of the pro R and pro-S C4-H bonds of NADH in solution and when bound to pig heart lactate (LDH) or mitochondrial malate (mMDH) dehydrogenases. This is achieved by specifically deuterating the C4 pro-R or pro-S hydrogens of NADH and determining the frequencies of the resulting C4-D stretches by Raman difference spectroscopy. We find that the frequencies of the two C4-D stretching modes for the two bonds are essentially the same for the unliganded coenzyme. On the other hand, the position of the pro-S-[4-2H]NADH stretch shifts upward by about 23-30 cm-1 in its binary complex with either lactate or malate dehydrogenase relative to that observed in solution, while that for the bound pro-R-[4-2H]NADH is relatively unchanged. The fact that the frequency of the pro-R hydrogen is not significantly affected during complex formation suggests that the rate enhancements for reaction of substrate with NADH brought about by both pig heart LDH and mMDH apparently do not involve either stabilization or destabilization of the pro-R hydrogen of NADH in enzyme-coenzyme binary complexes, in agreement with previous chemical studies. That these proteins are able to regulate the frequencies of the two C4-D bonds differentially, and hence the electronic distributions in these bonds, has important implications for the stereochemical reactions catalyzed by the NAD dehydrogenases, and this is discussed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1599931 TI - Kinetic studies on CO binding to reconstituted myoglobins with four synthetic hemes; structural control in ligand binding to myoglobin. AB - Examination was made of CO binding reactions to four kinds of modified sperm whale myoglobin (Mb), whose heme was reconstituted by iron complexes of synthetic porphyrins such as porphine (Por), meso-tetramethylporphyrin (TMeP), meso tetraethylporphyrin (TEtP) and meso-tetra(n-propyl)porphyrin (TnPrP), using flash photolysis and stopped-flow methods. The CO association rate was found to be 5- to 20-times and dissociation rate 10- to 36-times accelerated by replacement with synthetic hemes. These features could be explained based on characteristic structures of modified Mbs indicated by X-ray crystallography. The side chain of Arg-45 protruded from the heme vicinity into the solvent region and heme was tilted by interactions of meso-alkyl side chains with surrounding peptides, resulting in the formation of widely opened channels and pockets for ligand passage. These structural features indicate the CO ligand to more easily enter or exit from heme pockets of reconstituted myoglobins, compared to native Mb. PMID- 1599932 TI - Cofactor-directed inactivation by nucleophilic amines of the quinoprotein methylamine dehydrogenase from Paracoccus denitrificans. AB - Phenylhydrazine, semicarbazide, aminoguanidine, hydrazine, and hydroxylamine each irreversibly inactivated methylamine dehydrogenase from Paracoccus denitrificans and caused changes in the absorbance spectrum of the protein-bound tryptophan tryptophylquinone [TTQ] prosthetic group. Different spectral perturbations were observed on reaction with each of these inactivators. In each case a stoichiometry of 2 mol per mol of enzyme (1:1 per cofactor) was required to observe complete modification of the absorbance spectrum. Identical changes were observed in the presence and absence of oxygen. The reactions of hydrazine and hydroxylamine were very rapid, with stoichiometric inactivation occurring in less than 30 s. Inactivation by phenylhydrazine and semicarbazide exhibited apparent bimolecular kinetics and second order rate constants for inactivation, respectively, of 25 min-1 mM-1 and 39 min-1 mM-1. In contrast, inactivation by aminoguanidine exhibited saturation behavior and kinetic parameters of KI = 2.5 mM and kinact = 0.5 min-1 were obtained. Ammonium salts did not inactivate the enzyme, but were reversible competitive inhibitors with respect to methylamine. A Ki of 20 mM was obtained for ammonium chloride. A mechanism for the reactions of these compounds with the TTQ cofactor of methylamine dehydrogenase is proposed, and the relationship of these data to the mechanisms of interaction of these compounds with o-quinones and other quinoproteins which possess TTQ and other quinone cofactors is discussed. PMID- 1599933 TI - Purification and characterization of an alpha 1-antichymotrypsin-like 66 kDa protein from the human breast cancer cell line, MCF-7. AB - The synthesis of a 66 kDa protein immunoreactive with antibodies to human alpha 1 antichymotrypsin (alpha 1-ACT) is induced by estradiol (E2) in the human breast cancer cell line MCF-7. We have purified this alpha 1-ACT-like 66 kDa protein from medium conditioned by MCF-7 cells, performed a comparative physico-chemical characterization with serum alpha 1-ACT, and analysed its presumed positive regulatory effect on growth of MCF-7 cells. The 66 kDa protein is a functional antiproteinase which is antigenically identical to serum alpha 1-ACT. The 66 kDa protein does however deviate from serum alpha 1-ACT with respect to mol. wt. and pattern of microheterogeneity, the molecular mechanism for this is probably an incomplete glycoprotein processing in the MCF-7 cells. The results of our growth experiments suggest that the 66 kDa protein is a minor positive growth regulatory factor, which may contribute to breast carcinoma cell proliferation in a cooperative manner. PMID- 1599934 TI - Identification of the bactericidal domain of lactoferrin. AB - We report the existence of a previously unknown antimicrobial domain near the N terminus of lactoferrin in a region distinct from its iron-binding sites. A single active peptide representing this domain was isolated following gastric pepsin cleavage of human lactoferrin, and bovine lactoferrin, and sequenced by automated Edman degradation. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. Synthetic analogs of this region similarly exhibited potent antibacterial properties. The active peptide of bovine lactoferrin was more potent than that of human lactoferrin having effectiveness against various Gram negative and Gram-positive bacteria at concentrations between 0.3 microM and 3.0 microM, depending on the target strain. The effect of the isolated domain was lethal causing a rapid loss of colony-forming capability. Our studies suggest this domain is the structural region responsible for the bacterial properties of lactoferrin. PMID- 1599935 TI - Amino acid sequence of a non-specific wheat phospholipid transfer protein and its conformation as revealed by infrared and Raman spectroscopy. Role of disulfide bridges and phospholipids in the stabilization of the alpha-helix structure. AB - A wheat non specific phospholipid transfer protein has been isolated from wheat seeds and its amino acid sequence reveals that it is composed of 90 residues for a molecular weight of 9607. From the comparison of its sequence with those of the eight known proteins of the same family, hypotheses on the role of some conserved residues in the transfer activity can be made. The conformation of this protein has been studied by Raman and Fourier transform infrared spectroscopy and this is the first report on the structure of non specific plant phospholipid transfer proteins. As opposed to previous studies on the structure prediction from the amino acid sequence, the results obtained show that plant non specific phospholipid transfer proteins are not almost entirely composed of beta-sheets. Instead, infrared results show that the wheat protein contains 41% alpha-helix and 19% beta-sheet structures, while 40% of the conformation is undefined or composed of turns. Raman spectroscopy shows that three disulfide bridges adopt a gauche-gauche-gauche conformation while the other exhibits a gauche-gauche-trans conformation, and that the two tyrosine residues are hydrogen bonded to water molecules. The cleavage of the disulfide bonds affects significantly the conformation of the protein, the extended confirmation being increased by 15% at the expense of the alpha-helix content. On the other hand, the binding of 1 palmitoyllysophosphatidylcholine to the protein leads to an increase of 8% of the alpha-helix content compared to the free protein. Secondary structure predictions from the amino acid sequence suggest that the binding of a phospholipid stabilizes helicity of the amphipathic helices while the reduction of disulfide bonds would affect the stability of the N-terminal helix. The extended structure located at the C-terminus is not affected. Finally, the wheat phospholipid transfer protein has no effect on the thermotropic behavior of large unilamellar vesicles of dimyristoylphosphatidylcholine while it increases the conformational order of the acyl chains of large unilamellar vesicles of dimyristoylphosphatidylglycerol in the liquid-crystalline state. No major conformational changes of the protein are observed when it is adsorbed to phospholipid vesicles. These results suggest that the helical structure is essential for the transfer activity without excluding a possible role of the C terminal extended structure on the adsorption to phospholipid vesicles. PMID- 1599936 TI - Characteristics of substrates and inhibitors in binding to rat liver L-tryptophan 2,3-dioxygenase: a Fourier transform infrared and kinetic study. AB - Infrared spectroscopy and steady-state kinetics were applied to rat liver L tryptophan 2,3-dioxygenase, in order to find relations between the structure and binding characteristics of its substrates and inhibitors. The binding characteristics were reflected by changes in the infrared CO stretch band(s) of an Fe(II)-CO complex of the enzyme upon addition of L-tryptophan and 12 analogs. The CO stretch band around 1961 cm-1 of the complex was not much affected by 1 methyl-D,L-tryptophan, a noncompetitive inhibitor, implying a binding at a site distant from the Fe(II)-CO vicinity. The spectral pattern was significantly changed by any of the other compounds which conserved an indole NH, indicative of its binding to the catalytic site. All substrates, which contained a complete CH(NH2)COOH group in addition to the NH, gave spectra similar to that of an L tryptophan-bound complex. Spectral changes caused by six inhibitors, which lacked the complete CH(NH2)COOH, were different from one another and from those by the substrates. Hence, for an analog, the indole NH is indispensable to bind to the catalytic site, and the CH(NH2)COOH is important to take a correct configuration appropriate to the catalytic reaction. The reason why L- and D-isomers of 5 hydroxytryptohan are not substrates, in spite of their conservation of the required functional groups and correct binding to the catalytic site, has been ascribed to a possible distortion of the protein structure in the heme pocket due to a strong hydrogen bond from the hydroxyl group to an amino acid side chain. PMID- 1599937 TI - Nanosecond study of fluorescently labeled troponin C. AB - The time-resolved extrinsic fluorescence of rabbit skeletal troponin C was studied with the protein labeled at Cys-98 with N-(iodoacetyl)-N'-(5-sulfo-1 naphthyl)ethylenediamine. Both the intensity and anisotropy decays followed a biexponential decay law, regardless of the ionic condition, pH, viscosity or temperature. The lifetimes and their fractional amplitudes were insensitive to Mg2+, and the lifetimes were also insensitive to Ca2+. In response to Ca2+ binding to all four sites, the fractional amplitude (alpha 1) associated with the short lifetime (tau 1) decreased by a factor of two, thus increasing the ratio of the two amplitudes alpha 2/alpha 1 from 1.6 to 4.3. These amplitude changes suggest the existence of two conformational states of TnC-IAEDANS, with the conformation associated with the long-decay component (tau 2) being promoted by saturation of the two Ca(2+)-specific sites. At pH 5.2 the ratio alpha 2/alpha 1 for the apo-protein was 3.5 indicating different relative populations of the two decay components when compared with pH 7.2. In the presence of Ca2+ at the lower pH, alpha 2/alpha 1 decreased to 2.1, suggesting a shift of the conformations in favor of the short-decay component. Thus Ca2+ elicited different conformational changes in TnC at the two pH values. The recovered anisotropies suggest that there were fast molecular motions that were not resolved in the present experiments, and some of these motions were sensitive to Ca2+ binding to the specific sites. These results support the notion of communication between the N domain and the C-terminal end of the central helix of troponin C. PMID- 1599938 TI - Species differences in liver type I iodothyronine deiodinase. AB - The type I iodothyronine deiodinase (ID-I) of liver is an important enzyme for the conversion of the prohormone thyroxine (T4) to the active thyroid hormone 3,3',5-triiodothyronine (T3). Because it is an integral membrane protein of low abundance, purification of ID-I from rat liver has proven to be difficult. We have analyzed ID-I in liver microsomal fractions from various animals to reveal possible species differences and to explore alternative sources for the isolation of the enzyme. ID-I was characterized by enzyme assay with 3,3',5' triiodothyronine (rT3) as the preferred substrate and by affinity-labeling with N bromoacetyl-[125I]T3 (BrAc[125I]T3). Labeled ID-I subunit was identified and quantified by SDS-PAGE and autoradiography. The Mr of ID-I in the species investigated varied between 25.7 and 29.1 kDa. Rat and dog liver microsomes had a markedly higher enzyme content than microsomes of human, mouse, rabbit, cow, pig, sheep, goat, chicken or duck liver. Rat liver microsomes showed the highest ID-I activity of all species examined. Turnover numbers for ID-I varied between 264 and 1059 min-1, with rabbit and goat showing the highest values. However, dog liver ID-I displayed an exceptionally low turnover number of 78 min-1. In conclusion, ID-I has similar properties in all species examined with the notable exception of dog. PMID- 1599939 TI - Chemical modification of human placental glutathione transferase by pyridoxal 5' phosphate. AB - Incubation of GST pi from human placenta with 8 mM PLP resulted in a rapid loss of activity during the first 10 min, concomitant with a Schiff base formation. This inactivation was probably due to the formation of a reversible adduct between PLP and the enzyme. After sodium borohydride treatment this adduct was reduced and stabilized. Stoichiometry and peptide isolation studies showed that three lysine residues were modified during reaction of GST and PLP. Protection of the enzyme against inactivation was achieved in the presence of 4 mM GSH suggesting that at least one lysyl residue is associated with the substrate binding site. Peptide mapping by digesting the enzyme with trypsin revealed that lysine shielded by GSH is Lys-127. Our results suggest that this residue may play an important role in enzymatic activity. PMID- 1599940 TI - Aggregation of chymotrypsinogen: portrait by infrared spectroscopy. AB - Changes in the secondary structure and aggregation of chymotrypsinogen were investigated by infrared difference spectroscopy in conjunction with temperature and pressure tuning IR spectroscopy; both the amide I' band and side chain bands were studied. A prominent component of the amide I' band in the difference spectrum obtained upon cooling a chymotrypsinogen solution, or increasing the hydrostatic pressure, was observed in the region between 1627 and 1622 cm-1. Under denaturing conditions a white gel was formed, which is attributed to irreversible self-association or aggregation. This process was accompanied by the appearance of two new amide I' bands in the infrared spectrum of the protein: a very strong band at 1618 cm-1 and a weak band at 1685 cm-1. These bands are assigned to peptide segments with anti-parallel aligned beta-strands. PMID- 1599941 TI - Structural fluctuations and conformational entropy in proteins: entropy balance in an intramolecular reaction in methemoglobin. AB - The reversible intramolecular binding of the distal histidine side chain to the heme iron in methemoglobin is of special interest due to the very large negative reaction entropy which overcompensates the large reaction enthalpy. It may be considered as a prominent example of the ability of proteins (including enzymes) to provide global entropy in a local process. In this work new experiments and model calculations are reported which aim at finding the structural elements contributing to the reaction entropy. Geometrical studies prove the implication of the 20 residue E-helix being shifted by more than 2 A. Vibrational entropies are calculated by a procedure derived from the method of Karplus and Kushik. It turns out that neither the histidine alone nor the complete E-helix contribute more than 15 per cent of the required entropy. PMID- 1599942 TI - Plant thermal hysteresis proteins. AB - Proteins which produce a thermal hysteresis (i.e. lower the freezing point of water below the melting point) are common antifreezes in cold adapted poikilothermic animals, especially fishes from ice-laden seas and terrestrial arthropods. However, these proteins have not been previously identified in plants. 16 species of plants collected from northern Indiana in autumn and winter had low levels of thermal hysteresis activity, but activity was absent in summer. This suggests that thermal hysteresis proteins may be a fairly common winter adaptation in angiosperms. Winter stem fluid from the bittersweet nightshade, Solanum dulcamara L., also showed the recrystallization inhibition activity characteristic of the animal thermal hysteresis proteins (THPs), suggesting a possible function for the THPs in this freeze tolerant species. Other potential functions are discussed. Antibodies to an insect THP cross reacted on immunoelectroblots with proteins in S. dulcamara stem fluid, indicating common epitopes in the insect and plant THPs. PMID- 1599943 TI - Contributions to the S'-subsite specificity of papain. AB - The product ratio was analyzed for the papain-catalyzed acyl transfer from the specific acyl donor Mal-Phe-Ala-OEtCl to various nucleophilic amino components, ranging from amino acid amides to tripeptide amides. The data obtained are discussed in terms of binding specificity. From the structure-activity relationships for the S'1-P'1 interaction it follows that only three methyl(ene) groups can be accommodated in the S'1 subsite. Hydrophilic side chains are bound better to S'1 than indicated by their hydrophobicities. Negatively charged amino components are inefficient deacylating agents. However, there was no evidence for electrostatic contributions to the nucleophile binding. Amino components with bulky hydrophobic amino acid residues in the P'2 and in the P'3 position, respectively, are preferentially bound to Mal-Phe-Ala-papain. The results of this study can be applied to the planning of papain-catalyzed peptide synthesis reactions. PMID- 1599944 TI - H-NMR study of rabbit skeletal muscle troponin C: Ca(2+)-dependent interaction with mastoparan. AB - 1H-NMR spectroscopy is employed to study the interaction between rabbit skeletal muscle troponin (C (TnC) and wasp venom tetradecapeptide mastoparan. We monitored the spectral change of the following species of TnC as a function of mastoparan concentration: apoTnC, Ca(2+)-saturated TnC (Ca4TnC) and Ca(2+)-half loaded TnC (Ca2TnC). When apo-TnC is titrated with mastoparan, line-broadening is observed for the ring-current shifted resonance of Phe-23, Ile-34, Val-62 and Phe-72 and the downfield-shifted CH alpha-resonances of Asp-33, Thr-69 and Asp-71; these residues are located in the N-domain. When Ca4TnC is titrated with mastoparan, chemical shift change is observed for the ring-current shifted resonances of Phe 99, Ile-110 and Phe-148 and the downfield-shifted CH alpha-resonances of Asn-105, Ala-106, Ile-110 and Ile-146 and aromatic resonance of Tyr-109 and His-125; these residues are located in the C-domain. The resonance of Phe-23, Asp-33, Asp-71, Phe-72, Phe-99, Tyr-109, Ile-146, His-125 and Phe-148 in both N- and C-domains changes when Ca2TnC is titrated with mastoparan. These results suggest that mastoparan binds to the N-domain of apo-TnC, the C-domain of Ca4TnC and the N- and C-domains of Ca2TnC; the hydrophobic cluster in each domain is involved in binding. As mastoparan binds to TnC, the above resonances shift to their normal chemical shift positions. The stability of the cluster and the beta-sheet is reduced by mastoparan-binding. These results suggest that the conformation of the hydrophobic cluster and the neighboring beta-sheet change to a loose form. The stability of the N-domain of Ca2TnC and Ca4TnC increases when these species bind 1 mol of mastoparan at the C-domain. These results suggest a mastoparan-induced interaction between the N- and C-domains of TnC. PMID- 1599945 TI - Purification, characterization and gene cloning of a novel glutamic acid-specific endopeptidase from Staphylococcus aureus ATCC 12600. AB - Twenty strains of Staphylococcus aureus from ATCC type cultures and strains found in clinical studies were cultivated, and their endopeptidase activity specific for glutamic acid was surveyed using benzyloxycarbonyl-Phe-Leu-Glu-p-nitroanilide (Z-Phe-Leu-Glu-pNA) as a substrate. The activity was found in two of the strains, ATCC 12600 and ATCC 25923. A glutamic acid-specific proteinase, which we propose to call SPase, was purified from the culture filtrate of S. aureus strain ATCC 12600 by a series of column chromatographies on DEAE-Sepharose twice and on Sephacryl S-200. A single band was observed on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) of the purified SPase. The molecular weight of the proteinase was estimated to be 34000 by SDS-PAGE. When synthetic peptides and oxidized insulin B-chain were used as substrates, SPase showed the same substrate specificity as V8 proteinase, EC 3.4.21.9, which specifically cleaves peptide bonds on the C-terminal side of glutamic acid and aspartic acid. Examination with p-nitroanilides of glutamic acid and aspartic acid as substrates, however, revealed that both proteinases are highly specific for a glutamyl bond in comparison with an aspartyl bond. To elucidate the complete primary structure of SPase, its gene was cloned from genomic DNA of S. aureus ATCC 12600, and the nucleotide sequence was determined. Taking the amino acid sequence of SPase from the NH2-terminus to the 27th residue into consideration, the clones encode a mature peptide of 289 amino acids, which follows a prepropeptide of 68 residues. SPase was confirmed to be a novel endopeptidase specific for glutamic acid, being different from V8 proteinase which consists of 268 amino acids. PMID- 1599946 TI - Secondary structure formation precedes tertiary structure in the refolding of ribonuclease A. AB - The kinetics of refolding of ribonuclease A were monitored by circular dichroism (CD), tyrosine fluorescence and absorbance in the -40 to -10 degrees C range using a methanol cryosolvent. The native-like far-ultraviolet CD signal returned in the dead-time of the mixing, whereas the native absorbance and fluorescence signals returned in a multiphasic process at rates several orders of magnitude more slowly. Thus the secondary structure was formed much more rapidly than the tertiary structure. In addition, the absorbance signal showed evidence of an early intermediate in which one, or more, tyrosine residues was in a transiently more polar environment. A total of four kinetic phases were observed by absorbance in refolding, the slowest two of which had energies of activation consistent with proline isomerization. A refolding scheme involving initial hydrophobic collapse, concurrent with secondary structure formation, followed by much slower rearrangement to the native tertiary structure is proposed. PMID- 1599947 TI - The effects of ionic strength on the self-association of human spectrin. AB - The self-association of human spectrin has been studied by means of sedimentation equilibrium in the analytical ultracentrifuge at pH 7.5 and over a range of ionic strength from 0.009 to 1.0 M. Increasing ionic strength above 0.1 M reduces the equilibrium constants for all of the measurable steps in the self-association reaction. These results support the concept of charge-charge interactions stabilizing the tetramer and higher oligomers with respect to the heterodimer. In addition, increasing ionic strength brought about a dissociation of the heterodimer to component polypeptide chains. Dissociation to the heterodimers is also enhanced with a decrease in ionic strength below 0.05 M. This low ionic strength-dependent dissociation is consistent with generalised electrostatic repulsion; however, this effect also correlates with some loss of alpha-helical content as revealed by circular dichroism. The secondary, tertiary and quaternary structures may all be partially disrupted by electrostatic free energy at low ionic strength. PMID- 1599948 TI - Interconversion of D-fructose 1,6-bisphosphate and triose phosphates in human erythrocytes. AB - Aldolase and triose phosphate isomerase both display strict specificity towards the enantiomers of [1-3H]glycerone 3-phosphate. The enantiomer generated from D [1-3H]glyceraldehyde 3-phosphate produces 3HOH in the aldolase reaction, whilst the other enantiomer generated from D-[3-3H]fructose 1,6-bisphosphate is solely detritiated in the reaction catalyzed by triose phosphate isomerase. Advantage was taken of such a specificity to assess, in human erythrocytes exposed to either D-[3-3H]glucose or D-[3,4-3H]glucose, the extent of D-glyceraldehyde 3 phosphate sequential conversion to glycerone 3-phosphate and D-fructose 1,6 bisphosphate, relative to net glycolytic flux. At 37 degrees C and in the presence of 5.6 mM D-glucose, only 55% of the metabolites of D-[4-3H]glucose underwent detritiation in the reactions catalyzed by triose phosphate isomerase and aldolase. Such a percentage was further decreased at low temperature (8 degrees C) or lower concentrations of D-glucose (0.2 and 1.0 mM). However, when the erythrocytes were exposed to menadione, the increase in 3HOH production from either D-[3-3H]glucose or D-[3,4-3H]glucose indicated that the majority of the 3H atoms initially located on the C4 of D-glucose were recovered as 3HOH upon circulation through the pentose phosphate pathway. These findings suggest that, under physiological conditions, a large fraction of D-glyceraldehyde 3-phosphate generated from exogenous D-glucose may undergo enzyme-to-enzyme channelling in the glycolytic pathway. PMID- 1599949 TI - Calponin and tropomyosin interactions. AB - The interaction between chicken gizzard calponin and tropomyosin was examined using viscosity, light scattering, electron microscopy and affinity chromatography. At neutral pH, 10 mM NaCl and in the absence of Mg2+, calponin induced tropomyosin filaments to form paracrystals thus decreasing the viscosity while increasing dramatically the light scattering of the tropomyosin solution. Electron micrographs of the uranyl acetate stained calponin-tropomyosin complex showed the presence of spindle shaped paracrystals with regular striation patterns and repeating units of about 400 A. Under similar conditions, smooth muscle caldesmon also induced tropomyosin to form paracrystals. To localize the calponin-binding site on tropomyosin, binding of fragments of tropomyosin, generated by chemical and mutational means, to a calponin-affinity column was studied. The COOH-terminal tropomyosin fragment Cn1B(142-281) and the NH2 terminal fragment CSM-beta(1/8/12-227) bound to a calponin-affinity column with an affinity similar to that of intact tropomyosin; while the NH2-terminal fragment, Cn1A(11-127), did not bind, indicating that the calponin-binding site(s) resides within residues 142-227 of tropomyosin. To determine the involvement in calponin binding of the area around Cys-190 of tropomyosin, fragments with cleavage sites near or at Cys-190 were used. Thus, while fragments Cy2(190-284) and CSM-beta(1/8/12-200) bound weakly to the calponin-affinity column, fragment Cy1(1-189) did not. These results demonstrate that calponin binds to tropomyosin between residues 142 and 227, and that the integrity of the region around Cys-190 of tropomyosin is important for strong interaction between the two proteins. PMID- 1599950 TI - Polyclonal antisera specific for the proenzyme form of each calpain. AB - Each subunit of calpain (EC 3.4.22.17) is proteolytically modified when the enzymes are exposed to calcium. These cleavages appear to be important for regulating the proteolytic activity and calcium-sensitivity of the proteinases. We have synthesized peptides that correspond to the sites of autoproteolytic modification within the catalytic subunit of each calpain. Polyclonal antisera raised against these peptides are highly specific for the unmodified catalytic subunit of each calpain. The antiserum specific for the N-terminal epitope of milli-calpain was used to demonstrate an inverse relationship between the presence of this N-terminal peptide and casein hydrolysis. The antiserum specific for the N-terminal epitope of micro-calpain was used to demonstrate proteolytic modification of the catalytic subunit of mu-calpain in rat erythrocytes treated with ionomycin and calcium. PMID- 1599951 TI - Purification and characterization of two extracellular beta-glucosidases from Trichoderma reesei. AB - A major beta-glucosidase I and a minor beta-glucosidase II were purified from culture filtrates of the fungus Trichoderma reesei grown on wheat straw. The enzymes were purified using CM-Sepharose CL-6B cation-exchange and DEAE Bio-Gel A anion-exchange chromatography steps, followed by Sephadex G-75 gel filtration. The isolated enzymes were homogeneous in SDS-polyacrylamide gel electrophoresis and isoelectric focusing. beta-Glucosidase I (71 kDa) was isoelectric at pH 8.7 and contained 0.12% carbohydrate; beta-glucosidase II (114 kDa) was isoelectric at pH 4.8 and contained 9.0% carbohydrate. Both enzymes catalyzed the hydrolysis of cellobiose and p-nitrophenyl-beta-D-glucoside (pNPG). The Km and kcat/Km values for cellobiose were 2.10 mM, 2.45.10(4) s-1 M-1 (beta-glucosidase I) and 11.1 mM, 1.68.10(3) s-1 M-1 (beta-glucosidase II). With pNPG as substrate the Km and kcat/Km values were 182 microM, 7.93.10(5) s-1 M-1 (beta-glucosidase I) and 135 microM, 1.02.10(6) s-1 M-1 (beta-glucosidase II). The temperature optimum was 65-70 degrees C for beta-glucosidase I and 60 degrees C for beta-glucosidase II, the pH optimum was 4.6 and 4.0, respectively. Several inhibitors were tested for their action on both enzymes. beta-Glucosidase I and II were competitively inhibited by desoxynojirimycin, gluconolactone and glucose. PMID- 1599952 TI - Phosphorylation of pyruvate kinase type K is restricted to the dimeric form. AB - In the absence of glycolytic intermediate, fructose-1,6-bisphosphate, pyruvate kinase type K exists in the dimeric form and is readily phosphorylated, whereas in the same sample and the same conditions pyruvate kinase type M is present as a tetramer and is not phosphorylated. Addition of fructose-1,6-bisphosphate results in the association of dimeric K2 molecules to a tetrameric K4 enzyme as determined by gel filtration and cellulose acetate electrophoresis, with concomitant loss of the capacity of the K isozyme to become phosphorylated. Phosphorylated K2 dimers can also tetramerize, but with a low recovery of the radiolabel, suggesting a fructose-1,6-bisphosphate induced dephosphorylation or selective degradation. The dimeric K isozyme is enzymatically active; inactive K type monomers can be detected by immunoblot analysis in the absence of fructose 1,6-bisphosphate, but no phosphorylated pyruvate kinase is present in this fraction. The formation of K4 tetramers can not be accomplished by the substrate phosphoenolpyruvate. Fructose-1,6-bisphosphate is an allosteric activator of pyruvate kinase type K and induces hyperbolic saturation curves for phosphoenolpyruvate. In contrast, in the absence of effectors, pyruvate kinase type M exhibits Michaelis-Menten kinetics, but sigmoidal curves can be induced by the amino acid phenylalanine. However, even in the presence of phenylalanine, the M-type maintained its tetrameric configuration and did not serve as a substrate in the phosphorylation reaction. These findings argue for the importance of subunit interaction in the regulation of phosphorylation of pyruvate kinase. PMID- 1599953 TI - Immunochemical characterization of developmental changes in rat hepatic hydroxysteroid sulfotransferase. AB - A major isoenzyme of hepatic androsterone-sulfating sulfotransferase (AD-ST) was purified from adult female rats. The activity was purified 122-fold over that found in the cytosol and showed a single protein band with a subunit molecular mass of 30 kDa after sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified enzyme exhibited four isoelectric variants of subunits on denaturing isoelectrofocusing gels (pI = 5.8, 6.1, 6.7 and 7.2). Rabbit antiserum raised against the enzyme specifically detected AD-ST polypeptide in rat liver cytosol. Immunoblot analysis of liver cytosol from female and male rats at various ages showed good correlation between the levels of AD-ST activity and AD-ST polypeptide. Significant levels of AD-ST activity and polypeptide were detected in senescent male rats, though normal adult male rats have very low levels of AD ST activity and protein. The relative content of the isoelectric variants of AD ST were different in liver cytosol of weanling and adult females, indicating that age- and gender-related alterations of hepatic AD-ST activity are primarily determined by the levels of AD-ST polypeptide and the relative amounts of the four isoelectric variants of the enzyme. PMID- 1599954 TI - Separation of porcine pepsinogen A and progastricsin. Sequencing of the first 73 amino acid residues in progastricsin. AB - Porcine pepsinogen A (EC 3.4.23.1) and progastricsin (EC 3.4.23.3) have been separated by chromatography on DEAE-cellulose followed by chromatography on DEAE Sepharose. Agar gel electrophoresis at pH 6.0 showed the presence of three components of pepsinogen A and two of progastricsin. During activation at pH 2 a segment of 43 amino acid residues (the prosegment peptide) is cleaved from the N terminus of progastricsin. The sequence of this was determined; in addition, the first 30 residues of gastricsin were sequenced. The sequence of the first 73 amino acid residues of progastricsin shows an overall identity with progastricsins from man, monkey and rat of 67%. The overall identity with other zymogens for gastric proteinases is 27%. The highly conserved Lys36p (pig pepsinogen A numbering) is changed to Arg in porcine progastricsin. PMID- 1599955 TI - Alkaline treatment of muscle microsomes releases amphiphilic and hydrophilic forms of acetylcholinesterase. AB - To obtain information about the mode of attachment of amphiphilic monomers of acetylcholinesterase (AChE) in sarcoplasmic reticulum (SR) of skeletal muscle, attempts were made to release the enzyme by alkaline hydroxylamine. About half of the activity measured in microsomes preincubated with 0.5% (w/v) Triton X-100 is detached by incubation of SR with bicarbonate buffer (pH 10.5). Addition of 1 M hydroxylamine to the alkaline buffer did not improve enzyme solubilization. Molecular forms of 16S (A12), 10.5S (G4) and 4.0S (G1) are separated by sedimentation analyses of Triton X-100 or bicarbonate-solubilized AChE. Monomeric AChE, released under alkaline conditions (G1A), displays amphiphilic properties. G1A, but not G4 and A12, forms are retained in a phenyl-Sepharose column and this allows its separation from hydrophilic forms. Isolated monomers extracted with Triton X-100 (G1D) or alkaline buffer showed identical kinetic behaviour. The two forms reacted with lectins in a similar manner. However, thermal inactivation experiments revealed that about 90 and 40% of the activity in the G1D and G1A forms were lost by heating at 50 degrees C, following the same rate constant (k = 0.130 min-1). Addition of Triton X-100 to the G1A form leads to an increase of its thermal sensitivity, the enzyme being fully inactivated very rapidly (k = 0.230 min-1). The results suggest that the hydrophobic moiety of the enzyme might be exposed or hidden depending on the environmental hydrophobicity. Changes in the composition of the solvent will determine the final conformational state of the protein. PMID- 1599956 TI - Estramustine-phosphate binds to a tubulin binding domain on microtubule associated proteins MAP-2 and tau. AB - Estramustine-phosphate (EMP), a phosphorylated conjugate of estradiol and nor nitrogen mustard binds to microtubule-associated proteins MAP-2 and tau. It was shown that this estramustine derivative inhibits the binding of the C-terminal tubulin peptide beta-(422-434) to both MAP-2 and tau. This tubulin segment constitutes a main binding domain for these microtubule-associated proteins. Interestingly, estramustine-phosphate interacted with the synthetic tau peptides V187-G204 and V218-G235, representing two major repeats within the conserved microtubule-binding domain on tau and also on MAP-2. This observation was corroborated by the inhibitory effects of estramustine-phosphate on the tau peptide-induced tubulin assembly into microtubules. On the other hand, the nonphosphorylated drug estramustine failed to block the MAP peptide-induced assembly, indicating that the negatively charged phosphate moiety of estramustine phosphate is of importance for its inhibitory effect. These findings suggest that the molecular sites for the action of estramustine-phosphate are located within the microtubule binding domains on tau and MAP-2. PMID- 1599957 TI - The use of fluorescence detection and internal lane standards to size PCR products automatically. AB - We have developed chemical procedures, optical and electrophoretic instrumentation and computer software automate the analysis of polymerase chain reaction (PCR) products. DNA molecules labeled with up to four different fluorescent dyes are analyzed within a single electrophoresis gel lane. A size calibration curve is created for each electrophoresis lane from the electrophoretogram of uniquely labeled DNA fragments belonging to an internal lane standard that co-electrophoreses with the PCR products. The unknown molecular lengths of PCR products are automatically calculated from the calibration curve. Data from control experiments with DNA segments of known molecular length demonstrate the accuracy and precision of such sizing. This system has been applied to the analysis of PCR products for research in the areas of human identification, genetic mapping and genetic disease. PMID- 1599958 TI - Rapid (ten-minute) pore-gradient electrophoresis of proteins and peptides in Micrograd gels. AB - Precast gradient gels of short migration length (25 mm) have been developed to provide rapid electrophoretic separation without loss of resolution. These Micrograd gels have been prepared in gel ranges (conventional and unique) to match pore-gradient electrophoresis conditions to proteins/peptides ranging in size from several hundreds to millions. The Hylinx Micrograd gel combines an extreme gel range (6 to 48% polyacrylamide) with a novel crosslinker to provide sieving of polypeptides, and pore-limit electrophoresis of the smallest proteins (e.g. insulin monomer). All gel ranges (such as 3 to 30%) provide zone sharpening in routine analysis of conventional protein mixtures (e.g. serum) within 10 min electrophoresis at 200 to 300 volts. The gels are thin (1 mm) and thus stain quickly, but the gel cassette is of conventional overall width (83 mm), thus fitting many apparatus designs and accommodating 12 samples. The gels are finding valuable use in screening applications, requiring the electrophoretic analysis of many samples, and in cases where a rapid answer is needed, such as monitoring protein purification. The gels have proved particularly useful, in-house, for the latter application in developing Gradipore's new large-scale preparative electrophoresis system, the Gradiflow. PMID- 1599959 TI - Identification of a haptoglobin-hemoglobin complex in the Alaskan Least Cisco (Coregonus sardinella). AB - The hemoglobin and a hemoglobin binding protein have been characterized in the Arctic fish (Coregonus sardinella). The evolutionary significance of the hemoglobin and plasma protein differences between fish and mammals is still unresolved. Blood samples from the Alaskan Least Cisco were separated into plasma and hemoglobin fractions and the proteins in these fractions were analyzed both by alkaline agarose gel electrophoresis, by isolelectric focusing, and by capillary electrophoresis. Staining the plasma proteins gels with o-dianisidine revealed hemoglobin containing protein complexes. A hemoglobin-containing band was observed in hemolyzed plasma which did not migrate with free hemoglobin, and is believed to be hemoglobin-haptoglobin complex. Size exclusion chromatography further characterized the hemoglobin as disassociating freely into dimers, and hemoglobin-haptoglobin complex having a molecular weight greater then 200,000 daltons. PMID- 1599960 TI - Haloperidol induced CSF protein variations in schizophrenic patients: as studied by two-dimensional electrophoresis. AB - High resolution two-dimensional electrophoresis of cerebrospinal fluid (CSF) from 10 schizophrenic patients demonstrated a 21% average difference in the number of proteins which could be detected in patients undergoing haloperidol therapy when compared with CSF from the same patients after withdrawal from neuroleptic treatment. Proteins affected were trace proteins, as we found no significant variation in either the total CSF protein content or the integrated protein density on each electrophoretic gel. Three mechanisms which might account for these observations are: (1) a small change in liver protein synthesis or degradation would have little if any visible effect on the concentration of major blood or CSF proteins, such as albumin, but it could significantly alter trace proteins, such as alpha 2-haptoglobin, since their concentrations are orders of magnitude less than that of the major proteins, (2) haloperidol might alter the blood-CSF protein filtration system which could affect the visibility of the trace proteins, and (3) proteins synthesized in the Central Nervous System (CNS) or enhanced in the CSF could be differentially affected by haloperidol. While additional research will be required to determine the basis for the effects of haloperidol on CSF proteins, the current studies provide information which may be helpful in delineating disease specific protein alterations from those induced by drug therapy. PMID- 1599961 TI - Electrokinetic and Kerr effect contributions to electric birefringence images of agarose electrophoresis gels. AB - Multilinear regression analysis is used to test a model (Lanan et al., 1991) for electric birefringence imaging (EBI) of DNA fragment bands in agarose electrophoresis gels. EBI signals attributed to localized electro-kinetic gel distortion and to intrinsic DNA birefringence are studied by fitting ethidium bromide fluorescence profiles to EBI results. Fluorescence polarization imaging (FPI) is used to assess the influence of localized gel distortion on nucleic acid orientation across a fragment band. It is shown that DNA aligns parallel, on average, with an applied electric field independent of its location within a band. DNA orientation varies as the 1.2 power in electric field strength under the conditions tested. PMID- 1599962 TI - Virulence associated proteins of Brucella abortus identified by paired two dimensional gel electrophoretic comparisons of virulent, vaccine and LPS deficient strains. AB - To identify molecular determinants of virulence, the proteins of Brucella abortus strains 2308 (virulent), S19 (vaccine) and lipopolysaccharide deficient rough mutants derived from each (RB51 and S19M3 respectively) were compared by 2-D gel electrophoresis. A total of 996 proteins were identified on autoradiographs of 2 D gels containing [35S]-labeled proteins from these four strains. Proteins differing qualitatively or quantitatively (greater than or equal to 10X) between 2308 and S19 are implicated in virulence and are identified by Mr and pI. Paired comparisons of proteins present in both 2308 and RB51 and missing in both S19 and M3 were used to make tentative identification of 14 putative virulence proteins representing primary expression of genetic differences between virulent and vaccine strains. 28 proteins and/or core lipopolysaccharide-protein complexes involved in the biosynthesis of lipopolysaccharide were identified by paired comparisons of proteins present in both smooth strains and missing in both rough strains. PMID- 1599963 TI - Two-dimensional gel analysis of serum apolipoprotein A-I isoforms: preliminary analysis suggests altered ratios in individuals with heart disease. AB - Apolipoprotein A-I (apo A-I), the major protein component of high-density lipoprotein, is quantified in a number of ways, typically by immunochemical methods. Commercial tests do not discriminate among isoforms of apo A-I. Two dimensional electrophoresis, however, segregates and differentiates these isoforms, primarily due to charge variations among the various species. Stained two-dimensional gels can be scanned using high-resolution laser densitometry, and the isoforms can then be quantified using image analysis software. Human sera from coronary heart disease (CHD) patients (n = 36) and sex-matched and close-age matched individuals (n = 36) with no known CHD were analyzed, to determine the relative abundance for each isoform within a given serum. In this preliminary study, we observed statistically significant differences between the two groups, suggesting altered post-translational processing from the proapo A-I and mature apo A-I isoforms to their adjacent isoforms for patients with histories of heart disease. In two instances, the P values were less than 0.005; in two others, P values were less than 0.001. PMID- 1599964 TI - Standards for nursing practice in British Columbia. PMID- 1599966 TI - Power shift. PMID- 1599967 TI - Elizabeth Cull. B.C.'s health minister is bringing health "closer to home". Interview by Bruce Wells. PMID- 1599965 TI - Taking first call. PMID- 1599968 TI - Guardianship legislation. PMID- 1599969 TI - Parents need help in coping with abuse. PMID- 1599970 TI - A united voice for nursing. PMID- 1599971 TI - Job shadowing. PMID- 1599972 TI - Epon resin infiltration and immunogold labelling of pituitary secretory granules after cryofixation versus chemical fixation. AB - The degree of infiltration of epoxy resin into pituitary secretory granules was evaluated using X-ray microanalysis of the concentrations of chlorine in the epoxy resins. The effectiveness of infiltration was tested after three different tissue preparation techniques: cryofixation+freeze-drying (CF-FD), glutaraldehyde fixation (GF)+chemical dehydration, and no fixation--no dehydration. Signs of marked incomplete infiltration were found in embedded unfixed tissue while the other two techniques showed 80% infiltration. Uneven penetration was seen after CF-FD and GF. The plastic surface demonstrated a mountain-like appearance over the secretory granules after immunocytochemistry of the glutaraldehyde fixed tissue, whereas the CF-FD tissue showed a less furrowed surface. This probably is due to contact with water, which swells those parts of the granules that are unprotected by the plastic embedding medium. Our findings may explain why it is possible to perform immunocytochemistry on Epon embedded tissue. PMID- 1599973 TI - Nonradioactive in situ hybridization with digoxigenin labeled DNA probes. AB - Nonradioactive in situ hybridization techniques are becoming increasingly important tools for rapid analysis of the topological organization of DNA and RNA sequences within cells. Prerequisite for further advances with these techniques are multiple labeling and detection systems for different probes. Here we summarize our results with a recently developed labeling and detection system. The DNA probe for in situ hybridization is modified with digoxigenin-labeled deoxyuridine-triphosphate. Digoxigenin is linked to dUTP via an 11-atom linear spacer (Dig-[11]-dUTP). Labeled DNA probes were hybridized in situ to chromosome preparations. The hybridization signal was detected using digoxigenin-specific antibodies covalently coupled to enzyme markers (alkaline phosphatase or peroxidase) or to fluorescent dyes. Color reactions catalyzed by the enzymes resulted in precipitates located on the chromosomes at the site of probe hybridization. This was verified by hybridizing DNA probes of known chromosomal origin. The signals were analyzed by bright field, reflection contrast and fluorescence microscopy. The results indicate that the new technique gives strong signals and can also be used in combination with other systems (e.g., biotin) to detect differently labeled DNA probes on the same metaphase plate. PMID- 1599974 TI - Microwell cluster for processing electron microscope sections for immunocytochemistry. AB - A microwell cluster was manufactured with silicone rubber for incubating thin sections for postembedding electron microscopic immunocytochemistry. The small size of the wells requires only minute amounts (as little as 5 microliters) of antisera and other valuable immunoreagents. The capillary action of the wells holds the incubation media and grids in place, even if the cluster is turned upside down, thus facilitating safe transport and storage of the sections to be stained. This silicone rubber microwell cluster can also be used as a die to imprint wells in Parafilm sheets to be used for the same purpose. PMID- 1599975 TI - Characterization of a phospholipase A2 in human serum. AB - Elevated catalytic activities of serum phospholipase A2 were measured in patients with inflammatory diseases. In contrast to human pancreatic phospholipase A2, the enzyme in serum of patients with non-pancreatic diseases was rather heat labile and showed a broad pH-optimum in the neutral range. Molecular sieving experiments revealed the existence of macro-molecular forms of the enzyme in serum which were cleaved into monomers of M(r) 14,000 in the presence of high salt concentrations. More than 100-fold purification was achieved by gel filtration chromatography on Sephadex G-100 in the presence of 2 mol/l KCl. Whether this serum phospholipase A2 and a secretory liver and platelet isoenzyme are identical remains to be established. PMID- 1599976 TI - Lipoamidase and biotinidase deficiency: evidence that lipoamidase and biotinidase are the same enzyme in human serum. AB - Late-onset multiple carboxylase deficiency depends on biotinidase deficiency and is inherited as an autosomal recessive trait. Lipoamidase deficiency in humans has not been previously reported, using the natural substrate lipoyllysine for lipoamidase. In this report we describe a simultaneous decrease in both lipoamidase and biotinidase activity in serum from a 21 month-old boy with a profound biotinidase deficiency. Lipoamidase activity in human serum was determined with both lipoyllysine (epsilon-N-(D,L-lipoyl)-L-lysine) and N-D,L lipoyl-p-aminobenzoate as substrates. Biotinidase activity was determined with both biocytin (epsilon-N-(D-biotinyl-L-lysine) and N-D-biotinyl-p-aminobenzoate as substrates. Our findings indicate that lipoamidase activity and biotinidase activity in human serim are due to the same enzyme, but a "residual activity" was usually found when N-D,L-lipoyl-p-aminobenzoate was used as a substrate. Compared with the activity in control serum, this "residual activity" was little affected by inhibition with biocytin, indicating that a small fraction of a modified biotinidase probably exists. PMID- 1599977 TI - Plasma phospholipase A2 in children with malignant disorders. AB - Forty nine children with various malignant disorders showed plasma phospholipase A2 catalytic activity concentrations in the range 0-48 U/l, and in 19 (39%) cases the values significantly exceeded 10 U/l. In 16 healthy children the catalytic concentration never exceeded 10 U/l. Of the 18 children with malignant lymphoma and 16 with acute leukaemia (14 of these with lymphoblastic leukaemia), 44% had plasma phospholipase A2 activities greater than 10 U/l. In 9 patients, an associated infection was either documented or could not be excluded. Of the remaining 40 patients, 33% had enzyme activities above 10 U/l. Although the determination of phospholipase A2 may not be relevant for the diagnosis of a malignancy, it may give an indication of the patient's reaction to the malignant process. PMID- 1599978 TI - Study of six antisera used for the immunonephelometric assay of human IgG. AB - The composition and performance of six commercial antisera for the immunonephelometric assay of IgG were studied. The analysis of the protein content of these reagents revealed significant differences in composition: the total protein contents ranged from 41 to over 130 g/l and gamma-globulins were twice to thirteen times higher than in a normal serum of the species. The antibodies found in these reagents were mostly IgG, with traces of IgM, and no IgA. Precipitation curves yielded by these antisera with a standard nephelometer showed a great diversity of performance. The very different shapes, the span of antigen concentrations and antibody dilutions necessary to obtain comparable quantities of precipitates further demonstrated the wide differences between these reagents. A method previously proposed by other authors was found to be inadequate. The failure of this method is attributed to the different conditions for the antigen-antibody reaction, as determined by the instrumentation used. It is concluded that the fundamental and classical criteria for testing antisera remain valid: specificity and the study of the precipitation curve to define the quantitative limits of the reaction. A simple universal method is inapplicable. PMID- 1599979 TI - Comparison of the ratio HDL-cholesterol/total cholesterol on the Reflotron vs. conventional wet chemistry methods. AB - A new HDL-cholesterol assay using solid phase reagent chemistry on the Reflotron has become available recently. This raises the question of whether the Reflotron now is suited for the determination of the ratio, HDL-cholesterol/total cholesterol, as a supplement to the lipid profile, viz. cholesterol, triacylglycerol and HDL-cholesterol. We investigated this ratio, which is an additional measure for the risk of coronary heart disease and found a good agreement between the Reflotron and conventional wet chemistry methods. We conclude that the Reflotron can be used for establishing the complete lipid profile of a patient. PMID- 1599980 TI - A collaborative trial for the evaluation of blood cholesterol measurement in clinical laboratories in Italy. AB - A collaborative trial for the evaluation of blood cholesterol measurement in Italy was carried out, with the use of two lyophilized controls, whose target values, respectively 4.42 and 6.21 mmol/l, were established by means of "definitive" methodology (isotope dilution/mass spectrometry). Results from 480 participants showed a somewhat broad dispersion (CV 6.1% and 6.3% respectively), and a definite bias (-0.25 mmol/l and -0.61 mmol/l respectively) with respect to the target values. The different analytical systems were characterized by different combinations of inaccuracy and imprecision; however, the bias observed for the higher concentration sample was a constant finding. The behaviour of the control materials, in comparison with that exhibited by patients' sera, was assessed in a manual enzymatic procedure and in the Kodak Ektachem 700 and Technicon Chem 1 systems. The peculiar property of one control material to behave differently from patients' sera in some analytical systems, i.e. the lack of commutability, was found to be partially responsible for the observed bias in the three methods studied. The importance of testing for commutability of the control materials to be used for the control of accuracy is stressed. PMID- 1599981 TI - Proposal of standard methods for the determination of enzyme catalytic concentrations in serum and plasma at 37 degrees C. II. Cholinesterase (acylcholine acylhydrolase, EC 3.1.1.8). Working Group of Enzymes, German Society for Clinical Chemistry. PMID- 1599982 TI - On the clinical application of P300. PMID- 1599983 TI - P300 and conceptual loosening in normals: an event-related potential correlate of "thought disorder?". AB - Reduced amplitude of the P300 component of the event-related potential (ERP) has frequently been reported in schizophrenic patients and their first-degree relatives. The present study examined the relationship between this ERP measure of attentional processing and loosening of associations in normal university students (termed "allusive thinking"). Among male subjects, scores reflecting increased conceptual loosening, measured using the Lovibond scoring method for the Goldstein-Scheerer Object Sorting Test (OST), were significantly correlated with smaller P300 amplitude recorded during an auditory target detection task. There was no association between OST score and either performance of the target detection task or self-reported psychopathology. It is suggested that reduced P300 amplitude could reflect altered attentional processing in individuals with a constitutional trait factor of thought disorder. PMID- 1599985 TI - Effect of subject's family name on visual event-related potential in schizophrenia. AB - Visual event-related potentials (ERPs) were recorded from 15 schizophrenics and 15 age-matched and gender-matched controls, while they performed a modified version of the oddball paradigm. Each subject was required to detect target stimuli among a random sequence of stimuli under two conditions, name and color. In the name condition the stimulus sequence consisted of the subject's family name (deviant 18%), four other family names (standard 73%), and a city name (target 9%). In the color condition the respective stimuli were a pair of solid red circles, four white paired-arrows, and a pair of white plus and minus signs. ERPs elicited by stimuli contained triphasic potentials of P2, N2, and P3. In controls these waves were selectively enhanced for the subject's family name as compared with standards, whereas in schizophrenics no significant difference between the subject's family name and other names was observed. In contrast, selective enhancement for color deviants was observed in both subject groups. These results suggest that impairment of involuntary attention, especially for familiar and significant stimuli such as names in daily life, may underlie disturbances of attentionally controlled central processing in schizophrenia. PMID- 1599984 TI - Biochemical measures in patients with a somatoform pain disorder, before, during, and after treatment with amitriptyline with or without flupentixol. AB - The possible relationship between a number of biochemical parameters and measures of pain and depression was studied in chronic pain patients without a major depression. In a double-blind crossover study, patients were treated with amitriptyline combined with a low dose of flupentixol or placebo. We investigated whether pretreatment biochemical values correlated with initial data on pain and/or depression, or whether they had predictive value for treatment outcome. We also studied systematically the effect of both treatment regimes on the biochemical parameters themselves and their relation to the plasma levels of amitriptyline. From our results, the possible involvement of the serotonin system in somatoform pain disorder is confirmed and no direct relation with the noradrenergic system could be inferred. The lack of involvement of a number of putative, depression-related, biochemical parameters suggests that affective disorders and pain syndromes do not share all mechanisms in common. PMID- 1599987 TI - Fluvoxamine improves negative symptoms in treated chronic schizophrenia: an add on double-blind, placebo-controlled study. PMID- 1599986 TI - Changes in cerebral blood velocity after intravenous diazepam. AB - Cerebral blood velocity (CBV) was measured with transcranial Doppler in 6 normal right-handed male volunteers before and for 50 min after an intravenous injection of 0.1 mg/kg of diazepam and normal saline during 2 separate visits to the laboratory. Blood pressure, pulse rate, end tidal levels of carbon dioxide and mood changes were quantified before and after the injections. Diazepam injection was associated with significant increases in fatigue and sleepiness. There were no significant changes in end tidal carbon dioxide, respiration, pulse rate, and blood pressure after the injection. Postdiazepam CBV was significantly lower following diazepam compared to CBV following placebo. PMID- 1599988 TI - A genetic linkage study of schizophrenia to chromosome 5 markers in a northern Italian population. AB - Some recent findings report that the area 5q11.2-13.3 of chromosome 5 segregates with schizophrenia in an uncle-nephew pair (Bassett et al 1988). However, linkage studies between chromosome 5 markers loci and schizophrenia lead to different results: Sherrington et al (1988) found a positive linkage, whereas other groups of researchers found evidence against linkage (Kennedy et al 1988; St. Clair et al 1989; Detera-Wadleigh et al 1989; McGuffin et al 1990; Aschauer et al 1990; Crowe et al 1991). We have studied five Italian pedigrees segregating schizophrenia using a map of four markers for the chromosomal region 5q11.2-13.3. Linkage analyses revealed negative lod scores, and thus no evidence for linkage was obtained in our Italian families. PMID- 1599989 TI - Subclinical hypothyroidism in recurrent mania. PMID- 1599990 TI - Subcortical brain anatomy in anorexia and bulimia. PMID- 1599991 TI - Effects of a low-fat diet on brain serotonergic responsivity in cynomolgus monkeys. PMID- 1599993 TI - Blood tin concentrations in Alzheimer's disease. PMID- 1599992 TI - Stability of plasma gamma-aminobutyric acid with time in healthy controls. PMID- 1599994 TI - The myth of meridian therapy. PMID- 1599995 TI - Basal ganglia mineralization in psychiatry. PMID- 1599996 TI - Cholinergic activity and constraints on information processing. AB - In humans, close relationships are found between cholinergic activity and constraints placed on information processing operations. This is true for all operations where the effects of cholinergic activity have been studied. Studies of vigilance, memory, problem solving, stimulus processing and response processing are cited as illustrations. These studies suggest the hypothesis that cholinergic activity controls constraints in all information processing operations. Alternative hypotheses are proposed and experimental tests are suggested. PMID- 1599997 TI - P300, probability, and introverted/extroverted personality types. AB - Extreme introverted and extroverted subject groups (n = 24 each) containing equal numbers of male and females were assessed with the P300 (P3) component of the event-related potential (ERP). A two-tone auditory discrimination task in which the probability of the target stimulus varied systematically in different conditions (.20, .40, .60, .80) was used to elicit the ERPs. The P3 amplitude demonstrated a significant interaction between personality type, probability, and subject gender and was generally smaller for introverts than for extroverts. Female subjects tended to have larger overall P3 components than male subjects. P3 latency was not affected by the personality variable. The results support previous findings for ERP differences between introverts and extroverts and suggest that personality type differentially influences target stimulus probability effects. The findings are discussed in terms of individual differences in cortical activity on P3 amplitude and personality measures. PMID- 1599998 TI - Operant conditioning of P300. AB - This study demonstrates that operant conditioning may increase the P300 component of the event-related potential above a level obtained without contingent training. An experimental group of subjects was rewarded for producing large P300 amplitudes and was compared with a yoked control group which was rewarded on a random basis. During training the experimental subjects increased both the amplitude of the P300 and of a subsequent frontal negative slow wave relative to the control group. These training effects were independent of prestimulus potential shifts and occurred likewise for target and nontarget stimuli. PMID- 1599999 TI - Psychobiology of stage fright: the effect of public performance on neuroendocrine, cardiovascular and subjective reactions. AB - Subjective, neuroendocrine and cardiovascular functions were studied in high- and low-anxious musicians performing privately and publicly. Musicians were designated as "high-anxious" if they reported at least one episode of performance related tremor and as "low-anxious" if they never had experienced tremor while performing in public. All musicians performed privately and publicly while measurements of subjective, neuroendocrine and cardiovascular functions were made. Ratings of effort and distress were made prior to performance. Heart rate was monitored telemetrically before, during and after performance. Urinary epinephrine, norepinephrine and cortisol were sampled after public and private performance, respectively. Situational factors influenced most measures. Epinephrine, norepinephrine, cortisol, heart rate and ratings of distress but not effort increased from private to public performance. Heart rate was higher in high- than in low-anxious musicians during public performance but similar during private performance. The increase in neuroendocrine activation from private to public performance was similar in the high- and low-anxious groups. It is concluded that heart rate is a sensitive measure of both situational and individual determinants of performance-related distress. PMID- 1600000 TI - Relative changes in salivary Na+ and K+ concentrations relating to stress induction. AB - Three independent studies are reported in which periods of "relaxation" (A) and presumed stressors (B) were given to female students in an ABA design. The "stressors" were: (1) obligatory time-wasting activity; (2) a mental "IQ" test; and (3) delivering a speech. Saliva was collected immediately after "relaxation" and "stress" periods. "Stress" and "arousal" state were retrospectively assessed in experiments (1) and (2) by subject self-rating and in experiment 1 also by trained observers for the periods A and B. The molar [K+/Na+] ratio was determined for each saliva sample. The prediction that [K+/Na+] would increase with stress induction was supported by statistically significant results with stressors 1 and 2 (p less than 0.01), but speech delivery (3) resulted in a significant rise of [K+/Na+] after the stressor period. Correlations between [K+/Na+] and "stress" and "arousal" ratings also substantiated the prediction. PMID- 1600001 TI - Event related potentials, reaction time, and cognitive performance in idiopathic Parkinson's disease. AB - Sixteen non-demented patients with idiopathic Parkinson's disease (PD) with varying degrees of cognitive impairment and sixteen age-, sex- and education matched normal controls were examined with (1) an auditory oddball paradigm requiring counting or a motor response in separate determinations, (2) a reaction time task with movement time component and (3) a detailed clinical and neuropsychological test battery. Patients were impaired on a number of neuropsychological tests. They also showed an increased P2 and N2 latency, but no significant increase in P3 latency. Their response initiation times and reaction times during the oddball experiment were not different from controls, whereas movement time was significantly increased. Increased peak latencies, particularly for N2, were moderately associated with Parkinsonian motor impairment in patients and with the Benton Multiple Choice Visual Retention Test in patients and controls. Movement time was associated with P3 latency only in controls and in both groups with the Benton Multiple Choice Visual Retention Test. The observed pattern of results suggests that in non-demented PD patients ERP peak latencies, visuo-spatial task performance and Parkinsonian motor impairment share a significant degree of variance. While impairments in neuropsychological tests and delay in the earlier peaks P2 and N2 do not appear to be sensitive to medication with L-DOPA, normal P3 latencies might indicate good pharmacological symptom control in the absence of dementia. PMID- 1600002 TI - Catheter infection caused by Methylobacterium in immunocompromised hosts: report of three cases and review of the literature. AB - Three cases of catheter infection due to Methylobacterium extorquens are reported. Each patient had a history of acute leukemia and was immunocompromised; two had undergone bone marrow transplantation, and the third was receiving consolidation chemotherapy. All three patients survived after removal of the central venous catheter and antibiotic treatment. The clinical features of these cases are compared with those of the 12 previously reported cases of infection due to Methylobacterium species. PMID- 1600003 TI - A severe, unusual reaction to trimethoprim-sulfamethoxazole in patients infected with human immunodeficiency virus. AB - The clinical features of three patients with a life-threatening reaction to trimethoprim-sulfamethoxazole (TMP-SMZ) are presented along with seven other cases from the literature. All patients developed sudden fever and hypotension immediately after the administration of TMP-SMZ; usually this reaction occurred within approximately 2 weeks of completion of a previous course of the drug. All but one patient had a rash. Most patients were hypoxemic and developed diffuse pulmonary infiltrates. All patients responded rapidly to supportive care, while bacterial cultures remained negative. The presence, absence, or character of previous adverse reactions to TMP-SMZ did not predict subsequent severe reactions. Although its mechanism remains unclear, this reaction has features of both IgE-mediated anaphylaxis and cytokine (tumor necrosis factor)-mediated effects. We advise extreme caution, with close observation, when this drug is first readministered to patients who have experienced any TMP-SMZ-associated toxicity within the previous 6-8 weeks. PMID- 1600004 TI - Capnocytophaga bacteremia in a patient with Hodgkin's disease following bone marrow transplantation: case report and review. AB - Capnocytophaga is a gram-negative, capnophilic, facultatively anaerobic bacillus that normally inhabits the oral cavity. We report the case of a patient who developed capnocytophaga bacteremia following autologous bone marrow transplantation for Hodgkin's disease, and we review other reported cases of capnocytophaga bacteremia in immunocompromised patients. In our case infection followed pretransplantation conditioning and was associated with severe oral mucositis and neutropenia. Antibiotic therapy resulted in clinical resolution of infection. Capnocytophaga bacteremia should be included in the differential diagnosis of febrile neutropenia in immunocompromised patients (e.g., those undergoing bone marrow transplantation) especially in the presence of mucositis and gingival bleeding. PMID- 1600005 TI - Relapsing pneumococcal bacteremia in immunocompromised patients. AB - Relapse of Streptococcus pneumoniae bacteremia after appropriate therapy is thought to be rare, even in immunocompromised patients. We describe three immunodeficient patients who experienced repeated episodes of pneumococcal bacteremia within 8 weeks after receiving appropriate therapy. Serotyping and DNA fingerprinting of respective isolates strongly suggested that each patient's bacteremic relapse was caused by the same pneumococcal strain. Relapsing and recurrent infections with an identical pneumococcal strain, especially in immunodeficient individuals, may be more common than is generally appreciated. PMID- 1600006 TI - Antimicrobial resistance of Shigella isolates in Bangladesh, 1983-1990: increasing frequency of strains multiply resistant to ampicillin, trimethoprim sulfamethoxazole, and nalidixic acid. AB - The susceptibility to ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ) was determined for 15,824 isolates of Shigella obtained from patients attending a treatment center in Dhaka, Bangladesh, from 1983 through 1990 and for 520 isolates obtained during community surveys from 1988 through 1990. Susceptibility to nalidixic acid was determined for isolates obtained after 1985. In 1983 13% of isolates were resistant to ampicillin, 23.5% to TMP-SMZ, and 0.8% to both drugs. By 1990 51.2% of isolates obtained at the Diarrhea Treatment Centre were resistant to ampicillin, 47.7% to TMP-SMZ, and 40.5% to both drugs (for comparison with figures for 1983, P less than .001). Resistance to nalidixic acid increased from 0.8% in 1986 to 20.2% in 1990 (P less than .001). In 1990 71.5% of Shigella dysenteriae type 1 isolates were resistant to ampicillin, 68.5% to TMP SMZ, 67.7% to both drugs, and 57.9% to nalidixic acid. The resistance pattern of isolates obtained during community surveillance was similar to that of Treatment Centre isolates. In Bangladesh ampicillin and TMP-SMZ are no longer useful for treatment of infection with any species of Shigella, and nalidixic acid is no longer useful for treatment of infections due to S. dysenteriae type 1. PMID- 1600007 TI - Molecular studies on the aerolysin gene of Aeromonas species and discovery of a species-specific probe for Aeromonas trota species nova. AB - A large group of aeromonads and other enteric microorganisms were assayed for the presence of the aerolysin gene with use of DNA-DNA hybridization. Two DNA fragments corresponding to the regulatory region (aerC) and the structural gene (aerA) were used as probes for the detection of the aerolysin gene in these strains. Sequences corresponding to the aerolysin structural gene were widespread among Aeromonas isolates. In contrast, the aerC probe was much more selective, and sequences corresponding to the aerC region were detected in only a small subset of strains. Concurrent studies using numerical taxonomy and DNA hybridization with the aerC probe on a larger set of strains led to the identification of a distinct cluster of 14 presumed atypical Aeromonas sobria strains. These strains have recently been grouped into a new species designated Aeromonas trota. Hence, the DNA fragment aerC used in the study is a species specific gene probe for A. trota. The ability of the aerC probe to detect strains belonging to a single species suggests that there is selection pressure to maintain the clonality of this species. These results have important implications with respect to the evolution of "pathogenic profiles" among these medically important bacteria. PMID- 1600008 TI - Cryptococcal endophthalmitis: case report and review. AB - Cryptococcus neoformans is an opportunistic fungus with a predilection for infecting the meninges. Ocular sequelae of cryptococcal infections of the CNS usually include cranial nerve palsies or papilledema secondary to increased intracranial pressure. Intraocular cryptococcosis occurs less frequently, and over the last 23 years, only 27 cases have been reported, including the case presented here. Intraocular infection was most often manifested by chorioretinal lesions and vitritis. Underlying diseases were detected in only 11 (41%) of the 27 patients. Of note, ocular lesions preceded symptomatic meningitis in six (27%) of 22 patients with CNS involvement. For seven patients, the diagnosis was made by histologic examination of specimens of aqueous or vitreous humor; for another eight patients, the diagnosis was made after enucleation or at autopsy. Ocular involvement frequently led to severe visual loss; return of vision to normal was unusual. Early recognition and treatment may improve outcome for these patients. PMID- 1600009 TI - Streptococcal toxic shock syndrome due to noninvasive pharyngitis. AB - Serious infections due to group A beta-hemolytic streptococcus (GABHS) have been reported with increasing frequency in recent years. We report a case of toxic shock syndrome (TSS) due to GABHS pharyngitis in an otherwise healthy 14-year-old boy. The organism was found to produce toxin A. To our knowledge, this is the second reported case of streptococcal TSS associated with the production of toxin A that is not associated with an invasive disease and the first case associated with a documented rise in the level of antibody to the streptococcal toxin itself. Clinicians must be especially vigilant for this entity in patients who have streptococcal pharyngitis because early recognition and institution of aggressive supportive therapy can be lifesaving. PMID- 1600010 TI - Cutaneous manifestations of toxoplasmosis. AB - Toxoplasmosis is a common, largely asymptomatic infection. Early reports of acquired disease noted frequent dermatologic manifestations, whereas recent reviews of toxoplasmosis stress the lymphadenopathic presentation of the disease. We report the case of a patient with acute toxoplasmosis associated with a prominent macular and papular rash involving the palms and soles. We have reviewed the literature on dermatologic manifestations of acute acquired toxoplasmosis to underscore the importance of considering toxoplasmosis in the differential diagnosis of febrile illnesses with varied dermatologic presentations. PMID- 1600011 TI - beta-Lactamases of gram-negative bacteria: new challenges for new drugs. AB - The major emphasis in new drug design within the beta-lactam family has been on compounds less susceptible to hydrolysis by beta-lactamases and on combinations containing an enzyme-labile drug plus a beta-lactamase inhibitor. The introduction of such new compounds into clinical use has been followed by the discovery of novel mechanisms of resistance among gram-negative bacteria. These include the appearance of new enzymes, many of which are derivatives of older beta-lactamases. In addition, genes for certain broad-spectrum enzymes previously restricted to chromosomal sites have moved onto plasmids. There is now a greater appreciation of how alterations in enzyme expression--either alone or in concert with changes in drug permeation--can also lead to resistance. Clearly, recent events in the development of new beta-lactam agents have led to a new phase in the understanding of beta-lactam resistance. PMID- 1600012 TI - Enhancement of the effectiveness of antimicrobial therapy by muramyl peptide immunomodulators. AB - Besides promoting nonspecific resistance to experimental infection, muramyl peptide immunomodulators also potentiate the effects of antimicrobial agents. These substances have been evaluated in combination with appropriate anti infective agents in various models of bacterial, fungal, parasitic, and viral infection. For the combined regimens to be effective, the immunomodulator apparently must be administered prophylactically; anti-infective efficacy is then increased in situations where the muramyl peptide is capable of promoting at least some resistance to the infection independent of the antimicrobial agent. Adjunctive administration of the muramyl peptide may reduce the required dosages of potentially toxic antimicrobial agents and hence may lower the risk of toxic side effects. Because of the way in which they stimulate the inflammatory/immune systems, muramyl peptide immunomodulators may improve the outcome of therapy for infections in immunocompromised hosts. Initial clinical applications could involve the use of these immunomodulators in combination with antimicrobial agents as prophylaxis in high-risk individuals without overt infections. PMID- 1600013 TI - Indium-111-labeled human nonspecific immunoglobulin G: a new radiopharmaceutical for imaging infectious and inflammatory foci. AB - Indium-111-labeled human nonspecific immunoglobulin G (111In-IgG) is a newly developed radiopharmaceutical for imaging infectious and inflammatory foci. This article presents an overview of the literature concerning 111In-IgG scintigraphy. The current theory about the mechanism of accumulation suggests that 111In-IgG accumulates in lesions as a result of enhanced vascular permeability and subsequent entrapment of the radiolabeled protein. Human studies show excellent results in imaging bone and joint, abdominal, and intravascular infection. Of special interest is the ability to depict infectious foci in granulocytopenic patients. The value of 111In-IgG scintigraphy for detection of infection is compared with that of gallium-67, labeled-leukocyte, and technetium-99m (99mTc) nanocolloid scintigraphy. The significance of differences between 111In-IgG scintigraphy and two other new scintigraphic techniques, 99mTc-labeled IgG and 99mTc-labeled murine monoclonal anti-granulocyte antibody BW 250/183, are discussed. PMID- 1600014 TI - Update on mechanisms and prevalence of antimicrobial resistance in Haemophilus influenzae. AB - The prevalence of plasmid-mediated beta-lactamase production among clinical isolates of Haemophilus influenzae has increased globally since this characteristic was first recognized in 1972. Three nationwide surveillance studies conducted in the United States in the 1980s indicated that the rate of beta-lactamase production was approximately 30% among serotype b isolates and approximately 15% among nonencapsulated strains. The American studies also documented strains with resistance to chloramphenicol, tetracycline, trimethoprim sulfamethoxazole, rifampin, erythromycin, and certain older cephalosporins. Surveillance studies performed at about the same time in Canada, Europe, the United Kingdom, and several developing countries have also documented the prevalence of beta-lactamase-producing isolates and resistance among them to alternative agents such as chloramphenicol and tetracycline. Perhaps of greatest concern has been the isolation of H. influenzae (both serotype b and nonencapsulated strains) in the United States, Europe, and Asia that possess multiple antimicrobial resistance mechanisms. At the present time, H. influenzae isolates have not been detected that are resistant to either third-generation cephalosporins or fluoroquinolones. PMID- 1600015 TI - Infection caused by Streptococcus pneumoniae in children with sickle cell disease: epidemiology, immunologic mechanisms, prophylaxis, and vaccination. AB - The incidence of invasive infection due to Streptococcus pneumoniae is 6.9 infections per 100 patient-years among children with sickle cell anemia (SS genotype) who are less than 5 years of age; this rate is 30-100 times that which would be expected in a healthy population of this age. Splenic dysfunction is the major contributor to the increased risk. Postulated abnormalities of immunologic defense mechanisms, including synthesis of polyclonal IgG and IgM, the alternative complement pathway, opsonic activity, and T and B cell interaction, may also enhance risk. Preceding or concomitant viral infection is suspected of predisposing to pneumococcal infection, but no definitive data are available. The most prevalent pneumococcal serotypes causing disease in this setting include types 6, 14, 18, 19, and 23; these same serotypes are most frequently involved in "vaccine failure." Current evidence demonstrates only modest protective efficacy for contemporary pneumococcal vaccines in young patients with sickle cell anemia; thus alternative vaccines are required. Convincing evidence for a protective effect of antibiotic prophylaxis has been obtained in limited time trials. However, presently used prophylactic regimens pose problems related to compliance and provide imperfect protection; moreover, their optimal duration remains unknown. PMID- 1600016 TI - Ocular manifestations of Mycoplasma pneumoniae infection. AB - Ocular manifestations of Mycoplasma pneumoniae infection, other than conjunctivitis, are uncommon. Optic disk swelling, optic nerve atrophy, retinal exudates and hemorrhages, and cranial nerve palsies have been infrequently reported. We describe a 15-year-old patient who developed bilateral optic disk edema and iritis during an acute infection with M. pneumoniae and review the world literature on findings associated with ocular manifestations of infection with this pathogen. Although our patient experienced complete resolution of iritis and optic disk edema after 6 weeks, several patients described in the literature have experienced permanent sequelae as a result of optic neuropathy. PMID- 1600017 TI - A case of bacteremia due to resistant Streptococcus pneumoniae. AB - Streptococcus pneumoniae isolates with varying degrees of resistance to penicillin have been described. Strains that are highly resistant to penicillin (MIC, greater than 1 microgram/mL) and that are resistant to multiple antibiotics have been reported primarily in South Africa and Spain. We report a case of an adult patient with bacteremia due to S. pneumoniae that was highly resistant to penicillin (MIC, 4 micrograms/mL) and resistant to erythromycin, clindamycin, chloramphenicol, and co-trimoxazole who was successfully treated with vancomycin. PMID- 1600018 TI - Pancoast's syndrome due to pulmonary infection with Cryptococcus neoformans variety gattii. AB - Immunocompetent hosts usually do not require antifungal therapy for pulmonary cryptococcosis. We present a case of right lung mass and Pancoast's syndrome due to locally invasive Cryptococcus neoformans variety gattii in a normal host. Lobectomy followed by therapy with amphotericin B and flucytosine was curative. PMID- 1600019 TI - Infective endocarditis of a native valve due to Acinetobacter: case report and review. AB - A case of community-acquired infective endocarditis of a native valve that was caused by Acinetobacter calcoaceticus subspecies anitratus is presented. The previously reported cases are reviewed, and therapy for this disorder is discussed. The presence of a transient maculopapular rash involving the palms and soles but sparing the face is suggested as a possible early clinical clue to the diagnosis. Native valve endocarditis caused by Acinetobacter species is an acute, aggressive illness that is more likely to be fatal than the prosthetic valve form; of the previously described patients, five of 15 with native valve endocarditis and one of six with prosthetic valve endocarditis died. In the appropriate clinical setting, we recommend therapy with an antimicrobial agent known to be active against Acinetobacter organisms when blood cultures are reported to yield oxidase-negative, gram-negative coccobacilli until the final identification of the microorganism is known. PMID- 1600020 TI - A clinico-epidemiological study of epidemic typhus in Africa. AB - Epidemic, louse-borne typhus persists in the rugged, mountainous areas of Ethiopia and much of northeastern and central Africa as well as in the rural highlands of Central and South America, where the conditions of living favor the harboring of body lice and where antibiotic treatment and effective louse-control measures are unavailable. The historical significance and current epidemiology of typhus, including the reservoir of Rickettsia prowazekii in flying squirrels in the United States, are reviewed, and the clinical presentation, laboratory findings, and hospital course in the cases of 60 patients admitted with epidemic, louse-borne typhus to the St. Paul's Hospital in Addis Ababa, Ethiopia, are described. Treatment of this disease with oral doxycycline, tetracycline, or chloramphenicol prevents complications and results in prompt resolution of symptoms. PMID- 1600021 TI - Successful treatment of posttraumatic candidal myocarditis and pseudoaneurysm. PMID- 1600022 TI - Corynebacterium group D2 infection of a complex renal cyst in a debilitated patient. PMID- 1600023 TI - Luminal agents in the treatment of amebiasis. PMID- 1600024 TI - Leg abscess caused by Weeksella zoohelcum following a dog bite. PMID- 1600025 TI - Hyperkeratotic (Norwegian) scabies with gram-negative bacteremia as the initial presentation of AIDS. PMID- 1600026 TI - Mixed aerobic and anaerobic infection of the skeletal muscle in an intravenous drug user after cocaine injection. PMID- 1600027 TI - Life-threatening infections of the head and neck. PMID- 1600028 TI - Cytotoxicity testing of wound dressings using methylcellulose cell culture. AB - Wound dressings may induce cytotoxic effects. In this study, we check several, mostly commercially available, wound dressings for cytotoxicity. We used our previously described, newly developed and highly sensitive 7 d methylcellulose cell culture with fibroblasts as the test system. Cytotoxicity is assessed by monitoring cell growth inhibition, supported by cell morphological evaluation using light and transmission electron microscopy. We tested conventional wound dressings, polyurethane-based films, composites, hydrocolloids and a collagen based dressing. It was shown that only 5 out of 16 wound dressings did not induce cytotoxic effects. All 5 hydrocolloids were found to inhibit cell growth (greater than 70%), while cells had strongly deviant morphologies. The remaining wound dressings showed medium cytotoxic effects, with cell growth inhibition, which varied from low (+/- 15%), medium-low (+/- 25%) to medium-high (+/- 50%). Measurable cytotoxic effects of dressings detected in vitro are likely to interfere with wound healing when applied in vivo. The results are discussed in view of the clinical uses with contaminated wounds, impaired epithelialization or hypergranulation. PMID- 1600029 TI - Characterization of low-temperature-plasma treated silk fibroin fabrics by ESCA and the use of the fabrics as an enzyme-immobilization support. AB - Bombyx mori silk fibroin fabrics were treated with low-temperature-plasma using various gases. Alkaline phosphatase was immobilized onto the fabrics using the CNBr method. The enzyme activity was much improved by plasma treatment, especially when both O2 and CF4 were used. Using the ESCA technique it was found that the activities of the immobilized enzyme were strongly correlated with the C1s peak intensities of the atomic group -C-O-CF3. The apparent Michaelis constant for the enzyme decreased with increasing amounts of -C-O-CF3. PMID- 1600030 TI - Biocompatibility of the Vascugraft: evaluation of a novel polyester urethane vascular substitute by an organotypic culture technique. AB - To evaluate the biocompatibility of chemically and structurally modified polyurethane elastomers for use as blood vessel replacements, small squares of vascular prostheses were cultured in direct contact with endothelium from chick embryo aorta using an organotypic culture assay. The polyurethane materials tested were: Vascugraft (fibrous, open pore structure); commercial Hydrophilic Mitrathane prosthesis (high porosity, smooth surface, non-permeable, closed pore structure); experimental hydrophobic Mitrathane (less porosity but a fibrous, open pore structure, similar to Vascugraft). The commercial expanded polytetrafluoroethylene prostheses Impra and reinforced GORETEX were included as controls on account of their extensive clinical application in the femoropopliteal position. After 5 d incubation at 37 degrees C biocompatibility was assessed in terms of average area of migrating cells on the biomaterial, total number of cells surrounding the explant and level of adhesion between the cells and the biomaterial. The Vascugraft prosthesis promoted the growth of a continuous monolayer of cells on its surface. This behaviour was equivalent to Impra and reinforced GORETEX materials in terms of cell density and area of cell migration but appeared to be superior for cell adhesion. From a second series of cell culture tests, in which the extractables leached from the biomaterials were added to the nutrient medium, it was concluded that none of the biomaterials tested released cytotoxic contaminants. PMID- 1600031 TI - Use of ultrasound imaging and fluoroscopic imaging to study gastric retention of enzyme-digestible hydrogels. AB - Ultrasound and fluoroscopic imaging techniques were used to monitor the gastric retention of enzyme-digestible hydrogels in the canine stomach. When water was present in the stomach, ultrasound imaging was very effective in monitoring the position of the hydrogel in the stomach, solvent penetration into the gel, and the gastric tissue-gel interactions during peristalsis. Rubbery or fully swollen hydrogels appeared as sonolucent objects with ultrasound imaging. Partially swollen hydrogels displayed a sonolucent outer layer due to solvent penetration and a centrally located bright echo resulting from the acoustic impedance mismatch at the glassy/rubbery interface. The degree of gastric tissue-gel interactions during peristalsis was inversely related to the extent of lumenal distention with water. The effectiveness of peristaltic contractions in driving the hydrogel toward the pyloric sphincter increased as the water was emptied from the stomach. In the absence of water, imaging of the gel with ultrasound became difficult. For this reason, gels were loaded with diatrizoate meglumine/sodium diatrizoate to visualize in real-time using fluoroscopic imaging. Fluoroscopic imaging allowed only indirect assessment of the hydrogel movement during peristalsis and the degree of hydrogel swelling. The gastric retention of the hydrogel under fasted conditions was influenced by the degree of gel deformation in response to peristaltic contractions. Hydrogels with a low degree of deformation during peristalsis showed long gastric retention times. The utilization of ultrasound imaging and fluoroscopic imaging for monitoring dynamic events in the stomach provided information on hydrogel properties which are important to gastric retention. The use of these imaging techniques in the development of long-term oral drug delivery systems is described. PMID- 1600032 TI - Gel casting of resorbable polymers. 2. In-vitro degradation of bone graft substitutes. AB - Gel cast microporous materials produced from: slow resorbing, poly(L-lactide); fast resorbing, 50:50 poly(DL lactide coglycolide); and blends of these polymers have been characterized by weight loss, compression testing and thermal analysis after immersion in phosphate buffered saline (37 degrees C, pH 7.4) for times up to 6 months. Increasing weight loss and reduction in compressive properties with immersion time were measured. Blending reduces the rate of weight loss and material shrinkage relative to the copolymer. Thermal analysis of degraded samples revealed evidence of reorganization of the crystalline phase in poly(L lactide) and a crystalline component in the 50:50 copolymer, estimated at 5-7% of the original material content, which is probably responsible for gel formation. Thermograms of the blend are effectively a superposition of thermograms of the individual components. Gel casting shows potential for varying the resorption rate, form stability and compressive properties of micro/macroporous bone graft substitutes. PMID- 1600033 TI - Role of the glass phase in bioactive glass-ceramics. AB - Glass-ceramics, or composites with a glass-ceramic matrix prepared by controlled crystallization, almost invariably contain a residual glass phase. A suitable composition for the residual glass phase of bioactive glass-ceramics can be found approximately and controlled on the basis of calculation of a structural parameter Y, which in the simplified concept of the glass structure corresponds to the mean number of bridging oxygens per polyhedron in the glass lattice. PMID- 1600034 TI - Adsorption of baboon fibrinogen and the adhesion of platelets to a thin film polymer deposited by radio-frequency glow discharge of allylamine. AB - Platelet adhesion under static and flow conditions from a washed platelet suspension containing albumin to a polymer deposited by radio-frequency glow discharge of allylamine vapour on a poly(ethylene terephthalate) substrate was measured. Electron spectroscopy for chemical analysis was used to characterize the surface. Fibrinogen adsorption from a series of dilute plasma solutions to radio-frequency glow discharge/allylamine, measured using 125I radiolabelled baboon fibrinogen, increased with decreasing plasma dilution to a level much higher than that previously observed on polyurethanes. Elutability by sodium dodecyl sulphate of fibrinogen adsorbed from dilute plasma also increased with increasing plasma concentration, but fibrinogen preadsorbed from plasma became non-elutable when surfaces were stored in buffer for 5 d before contact with sodium dodecyl sulphate. Platelet adhesion to substrates which had been pre adsorbed with dilute plasma was measured using baboon platelets radiolabelled with 111In. Adhesion greatly decreased as the plasma concentration used for preadsorption increased, suggesting that non-specific platelet binding to the bare surface occurs when protein coverage is incomplete. Non-specific platelet binding was inhibited to varying degrees by preadsorption of different proteins to the surface. Platelet adhesion to surfaces preadsorbed with dilute (1.0%) baboon and human plasmas lacking fibrinogen (i.e. serum, heat-defibrinogenated plasma and congenitally afibrinogenemic plasma) was diminished compared with normal plasma. Addition of exogenous fibrinogen to the deficient plasma partially restored platelet adhesion to normal levels. Adhesion to surfaces preadsorbed with human plasma deficient in von Willebrand factor was comparable to that observed with normal plasma. The plasma preadsorption studies with fibrinogen deficient media suggested that adsorbed fibrinogen is necessary for platelet adhesion to the radio-frequency glow discharge/allylamine substrate at high protein coverage. However, since adhesion was greatly reduced when the plasma preadsorbed substrate was stored in buffer before platelet contact, the conformation of adsorbed fibrinogen is also important in mediating platelet adhesion to radio-frequency glow discharge. PMID- 1600035 TI - Dimensional stability of condensation silicone rubbers. AB - The linear shrinkage during 24 h after setting of a number of proprietary condensation silicone dental impression materials was studied. Weight loss and change in volume were measured over the same time period by weighing similar specimens in air and water. The weight-loss data conformed to a linear t1/2 plot, indicating that the loss of volatile material was diffusion controlled. From the diffusion coefficient so determined, linear shrinkage values predicted from the weight loss data were compared with the experimental results. For all except the highly-filled putty materials, the correspondence between theoretical and experimental data was reasonable; in the case of the putty materials, the shrinkage was very much greater than that predicted theoretically. This is possibly due to elastic memory effects consequent on moulding the putty materials. PMID- 1600036 TI - Review article: adrenergic control of motor and secretory function in the gastrointestinal tract. AB - The role that the sympathetic nervous system plays in modulating physiological processes in the gastrointestinal tract is becoming clearer. It is now known that motor, secretomotor and vasomotor activity are all modulated independently by the system. Adrenoreceptor stimulation appears to reduce intestinal contraction (except at sphincters), both via alpha-receptors which inhibit neurotransmitter release and also by a direct beta-receptor mediated action on smooth muscle. There is also evidence for tonic activity in the beta-adrenergic pathway, since beta-antagonists tend to increase contraction pressures. In animals alpha receptor-mediated pathways modulate fluid and electrolyte absorption, and alpha adrenergic agonists enhance net absorption and reduce net secretion. In man there is also evidence for a beta-adrenergic pathway which controls secretomotor function. Carbohydrate absorption appears to be dependent on activity in a beta adrenergic pathway, although this may be an indirect effect of changes in motor function. The time course of changes of both secretomotor and motor activity, induced by modulating sympathetic or adrenergic input, differ from the vascular changes indicating that the effects occur independently of each other. The gastrointestinal response to stressors is mediated, in part at least, by the sympathetic nervous system. Differences between individuals are likely to prove important. Since the sympathetic nervous system regulates gastrointestinal function both in the basal state and under stressful conditions, it will have effects on pathophysiological responses. Modification of such responses is likely to ameliorate symptoms, as has already been found for alpha-2-adrenergic agonists which have an antidiarrhoeal action. PMID- 1600037 TI - Review article: non-steroidal, anti-inflammatory drugs--the extending scope of gastrointestinal side effects. AB - The gastrointestinal side effects of non-steroidal, anti-inflammatory drugs extend beyond the duodenal bulb, and comprise a variety of lesions in all parts of the gut. Gastroduodenal ulceration is quantitatively dominant, although a major part of these lesions probably go unnoticed and heal spontaneously. Adaptation has been demonstrated for acetylsalicylic acid, and may be of importance for other substances as well. Non-steroidal anti-inflammatory drugs (NSAIDs) may induce relapse of inflammatory bowel disease. Permeability changes and mucosal inflammation are found in the small and large bowel in the majority of subjects taking NSAIDs, although the clinical significance is still not clear. Ulceration and perforation do, however, occur in this part of the gut as well. Treatment of NSAID-associated ulceration is similar to traditional ulcer treatment, possibly with extended treatment duration if the NSAID is continued. Prophylaxis is of some value, but is not required for every patient receiving an NSAID. PMID- 1600038 TI - Helicobacter pylori lipopolysaccharide stimulates gastric mucosal pepsinogen secretion. AB - The effect of Helicobacter pylori lipopolysaccharide on guinea pig gastric mucosal pepsinogen secretion has been examined using an Ussing chamber technique. Luminal addition of H. pylori lipopolysaccharide resulted in a fifty-fold stimulation of pepsinogen secretion compared to a twelve-fold increase with E. coli lipopolysaccharide. Electron microscopy showed marked degranulation of zymogen granules but no evidence of chief cell disruption. PMID- 1600039 TI - Compliance with anti-ulcer medication during short-term healing phase clinical trials. AB - Nine hundred and sixty-six patients' compliance with drug therapy of peptic ulcerations and reflux oesophagitis in four clinical trials were studied. The mean compliance rates varied from 90.5% (95% C.I. 89.0-92.1%) to 99.2% (95% C.I. 98.2-100.1%). Compliance declined significantly with increasing complexity of the dosage schedule in all trials, and toward the end of the treatment period in two of them. Patients with adverse events had a significant drop in compliance during the last part of the treatment period in one of the trials. There was a significant inter-centre variation in compliance. Overall, the variation was of little clinical significance. Patient compliance was independent of age, sex, use of alcohol and tobacco, effect of treatment, concomitant drug therapy and whether the pill was active drug or placebo. The study shows that a simplified dosage schedule, shortening of the treatment period, use of drugs with minimal side effects, and meticulous selection of centres could improve patient compliance with drug therapy in clinical trials. PMID- 1600040 TI - Circadian differences in pharmacological blockade of meal-stimulated gastric acid secretion. AB - The effects of identical morning (08.05 hours) and evening (20.05 hours) meals on intragastric pH were compared in 12 healthy volunteers receiving gastric antisecretory medication. Dosing included continuous intravenous infusion ranitidine (50 mg bolus followed by 12.5 mg/h) or a matching placebo which were randomly administered prior to and following 7 days of treatment with oral omeprazole (40 mg mane). Intragastric pH was monitored continuously using a tethered indwelling pH probe. Subjects were divided into groups, one of which began the pH monitoring session in the morning, the other in the evening. The median 24-h intragastric pH was significantly increased by all active dosing regimens (P less than 0.05). Combined omeprazole and ranitidine produced the highest median pH, 5.92. However, a breakthrough drop in intragastric pH occurred during the evening after all active dosing. Intragastric pH fell prior to and after consumption of the evening meal with median pH values less than 4 during all sessions. The evening meal led to significantly lower intragastric pH compared to the morning meal for omeprazole and the combined omeprazole and ranitidine dosing periods (P less than 0.05). There was no difference between morning and evening pH during the placebo or ranitidine periods. Ranitidine and omeprazole, either alone or in combination, were unable to prevent the meal stimulated decline in intragastric pH during the evening time period. PMID- 1600041 TI - Cholestasis in transplant patients--what is the role of cyclosporin? AB - The use of the drug cyclosporin is limited by toxicity. It would be advantageous to develop therapeutic monitoring of cyclosporin which would predict the development of clinical toxicity. In the present study, alternative methods of measuring cyclosporin levels were evaluated in a heterogenous population of transplant patients, comparing a fluorescent polarization immunoassay using a non specific polyclonal antibody, which measures both cyclosporin and its main metabolites, and a specific high-performance liquid chromatography assay for unchanged cyclosporin in blood. Neither measured variable alone correlated with laboratory evidence of renal toxicity (serum creatinine) or liver toxicity (serum glutamate transaminase, lactic dehydrogenase, alkaline phosphatase, or serum bilirubin). The relationship between metabolites and parent cyclosporin was quantitated using the ratio of cyclosporin levels determined by fluorescent polarization immunoassay over levels determined by high-performance liquid chromatography. A cohort of patients with markedly elevated ratios of cyclosporin were identified. When patients' data were reviewed collectively and individually there was a correlation between an elevated ratio and the serum bilirubin (r = 0.41, P less than 0.001). This association could be either due to cyclosporin as a cause of cholestasis or to cholestasis from any cause resulting in metabolite accumulation. Further studies are needed to clarify the role of cyclosporin in hepatic dysfunction and develop early, specific markers for this cyclosporin associated toxicity. PMID- 1600042 TI - Effect of treatment with cisapride alone or in combination with domperidone on gastric emptying and gastrointestinal symptoms in dyspeptic patients. AB - The effects on gastric emptying and gastrointestinal symptoms of treatment with cisapride alone and in combination with domperidone were investigated in 25 patients with chronic idiopathic dyspepsia. In a double-blind study, 9 patients were randomly assigned to receive cisapride 2.5 mg three times daily, and 8 patients to receive placebo. After 7 days of treatment, gastric emptying was significantly accelerated and the score of gastrointestinal symptoms was significantly reduced in patients treated with cisapride. Placebo treatment had no significant effect. A randomized, double-blind crossover study of 8 patients compared the effects of combined treatment with cisapride 2.5 mg plus domperidone 10 mg three times daily for 7 days against the effects of cisapride plus placebo. Administration of cisapride plus domperidone gave significantly higher gastric emptying and lower gastrointestinal symptoms than cisapride plus placebo. PMID- 1600043 TI - Antioxidant therapy for recurrent pancreatitis: biochemical profiles in a placebo controlled trial. AB - The usefulness of micronutrient antioxidant therapy for recurrent (non-gallstone) pancreatitis has recently been endorsed by a 20-week double-blind double-dummy cross-over trial in 20 patients. Treatment was delivered as two types of tablets, providing daily doses of 600 micrograms organic selenium, 9000 i.u. beta carotene, 0.54 g vitamin C, 270 i.u. vitamin E and 2 g methionine. We report antioxidant profiles in blood samples collected before entry, at the cross-over stage and upon completion of trial. Baseline serum concentrations of selenium, beta-carotene and vitamin E in the patients were significantly lower than in healthy controls, were unaltered by placebo and normalized by active treatment, but reverted to basal values in the subgroup that received placebo subsequently. The baseline serum concentration of a free radical marker--the 9-cis, 11-trans isomer of linoleic acid--was significantly higher in the patients than in controls, fell inexplicably in the placebo phase and fell further upon active treatment. Discriminant analysis eliminated the overlap in free radical marker and selenium concentrations between control sera on the one hand and baseline or post-placebo samples from the patients on the other: antioxidant treatment normalized the relationship between these biochemical parameters. Subnormal baseline serum levels of S-adenosylmethionine drifted downwards upon active treatment whereas a sharp rise was noted when a relapse of pancreatitis occurred during the placebo phase. The results confirm that adequate exposure to antioxidants in the active treatment phase was associated with amelioration of oxidative stress, and that there was no residual effect 10 weeks after switching over to placebo treatment. Furthermore, the paradoxical behaviour of S adenosylmethionine may imply that the beneficial effect of micronutrient antioxidants in recurrent pancreatitis is linked with preservation of the methionine trans-sulfuration pathway in pancreatic acinar cells. PMID- 1600044 TI - Sucralfate diminishes basal acid output without affecting gastrin, H. pylori or gastritis in duodenal ulcer patients. AB - Twelve patients with active duodenal ulcer disease and Helicobacter pylori infection were treated with 1 g sucralfate q.d.s. for 1 month. Ulcers healed in 8 of the 12 patients without an alteration in the H. pylori-associated antral gastritis. Sucralfate produced a significant fall in basal acid output in all the patients, from a median of 4.8 (range 2.1-12.1) to 1.6 (0.4-8) mmol/h, P less than 0.01, whereas peak acid output was unchanged from 41 (21-59) before to 38 (24-55) mmol/h after treatment. Basal plasma gastrin concentrations and the meal stimulated integrated gastrin response were not altered significantly by sucralfate: 8 (2-17) pmol/L and 732 (188-1045) pmol. min/L pre-treatment and 6 (2 17) pmol/L and 600 (140-1302) pmol. min/L post-treatment, respectively. The fall in basal acid output observed may contribute to prolonged duodenal ulcer remission after treatment with sucralfate. PMID- 1600045 TI - Short report: the effect of ranitidine on the post-prandial absorption of a low dose of alcohol. AB - Twenty healthy male subjects were studied twice using a double-blind, randomized placebo controlled, cross-over study design. Alcohol absorption (integrated 2-h plasma alcohol concentration, peak plasma alcohol concentration, and time to reach peak concentration) was measured after 8 daily doses of either placebo or 300 mg ranitidine. They were given alcohol, 0.15 g/kg of body weight by month after an evening meal. Compared with placebo, there was a trend towards higher integrated 2-h plasma alcohol concentrations (3.17 and 3.89 mg. h/dL, respectively, P = 0.07), and a statistically significant increase in mean peak plasma alcohol concentration after dosing with ranitidine (4.92 and 6.47 mg/dL, respectively, P = 0.05). PMID- 1600046 TI - Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical implications. AB - Serotonin (5-hydroxytryptamine; 5-HT) is found in the enteric nervous system where it has been implicated in controlling gastrointestinal motor function. A number of receptor or recognition sites have been identified in the gut, but recently most attention has focused on the 5-HT3 and 5-HT4 receptors. The functional role of the 5-HT3 receptor remains incompletely understood, but it is probably involved in the modulation of colonic motility and visceral pain in the gut. A number of selective 5-HT3 antagonists have been developed including ondansetron, granisetron, tropisetron renzapride and zacopride. While the substituted benzamide prokinetics (for example, metoclopramide, cisapride) also block 5-HT3 receptors in high concentrations, their prokinetic action is believed to be on the basis of their agonist effects on the putative 5-HT4 receptor. Some 5-HT3 antagonists have 5-HT4 agonist activity (for example, renzapride, zacopride) and others do not (for example, ondansetron, granisetron), while tropisetron in high concentrations is a 5-HT4 antagonist. Based on the pharmacological data, it has been suggested that specific 5-HT antagonists and agonists may prove to be beneficial in a number of gastrointestinal disorders including the irritable bowel syndrome, functional dyspepsia, non-cardiac chest pain, gastrooesophageal reflux and refractory nausea. In this review, the rationale for the use of these compounds is discussed, and the available experimental evidence is summarized. PMID- 1600047 TI - Review article: the treatment of Helicobacter pylori infection. AB - The discovery of Helicobacter pylori has stimulated great interest in its role in gastritis, non-ulcer dyspepsia and peptic ulceration. Treatment regimens to eradicate this organism from gastric mucosa have also received considerable attention. Current recommendations limit the use of triple drug combinations only to specific patient groups. PMID- 1600048 TI - The long-term management of duodenal ulceration using an H2-antagonist: symptomatic self-care compared with maintenance treatment. AB - In a 48-week study of 319 duodenal ulcer patients, symptomatic self-care with an histamine H2-receptor antagonist (flexible self-chosen dosing with cimetidine 0, 400 or 800 mg/day) was compared with maintenance treatment (cimetidine 400 mg nocte). The rate of withdrawal from the study was similar in both groups. The mean consumption of cimetidine 400 mg tablets was significantly higher in the maintenance group (7.2 vs. 5.4 tablets/week; P less than 0.0001), but the mean cumulative number of days with ulcer symptoms was higher in the symptomatic self care group (47.2 vs. 29.1 days in 48 weeks). The estimated number of days of work loss due to ulcer symptoms was similar in both groups (approximately 4 days in the 48 weeks of observation). It is concluded that symptomatic self-care using an H2-antagonist can provide not only an economic but also an effective strategy for the long-term management of uncomplicated duodenal ulceration. PMID- 1600049 TI - Does a previous course of tripotassium dicitrato bismuthate affect the subsequent chances of successful Helicobacter pylori eradication? AB - We have performed a retrospective study of 103 patients with either peptic ulcer or non-ulcer dyspepsia, infected with metronidazole-sensitive strains of Helicobacter pylori (H. pylori), who were treated with a combination of tripotassium dicitrato bismuthate and metronidazole for a period of at least two weeks. Dual therapy with tripotassium dicitrato bismuthate plus metronidazole showed similarly high eradication rates (greater than or equal to 80%) of H. pylori from patients irrespective of age, gender or clinical diagnosis. Most importantly, dual therapy achieved a similar eradication rate of H. pylori infection in 41 patients who had previously been treated with tripotassium dicitrato bismuthate alone or in combination with an antibiotic other than metronidazole. It therefore appears that H. pylori does not become resistant to treatment with tripotassium dicitrato bismuthate. PMID- 1600050 TI - Effects on the rat oxyntic mucosa of the histamine2-antagonist loxtidine and the H+, K(+)-ATPase inhibitor omeprazole. AB - The present study examined whether histamine could affect the growth of the enterochromaffin-like (ECL) cell and the parietal cell. The effects of the unsurmountable histamine H2-receptor antagonist loxtidine (80 mg/kg) and the H+, K(+)-ATPase inhibitor omeprazole (100 mumol/kg) were compared in female Sprague Dawley rats. Both drugs were given by gavage once daily for 3 months. Omeprazole induced a more pronounced and sustained hypergastrinaemia than loxtidine. In spite of marked hypergastrinaemia during most of the day, even in the loxtidine treated rats, the weights of the stomach and oxyntic mucosa were elevated only in the omeprazole-treated rats. The ECL cell density was slightly higher in the loxtidine- than in the omeprazole-treated rats. Both treatments elevated the gastrin-stimulated histamine release from the vascularly perfused stomach. The parietal cell density was unaffected by omeprazole treatment, whereas it tended to be reduced in the loxtidine-treated rats. Simultaneous administration of loxtidine and omeprazole reduced the sustained hypergastrinaemia induced by omeprazole given alone. The present study may indicate that histamine inhibits the growth of the ECL cell, but further studies are needed to elucidate if histamine has any trophic effect on the parietal cells. PMID- 1600051 TI - Pharmacokinetics and absolute rectal bioavailability of hydrocortisone acetate in distal colitis. AB - The hydrocortisone pharmacokinetic profiles of hydrocortisone acetate foam (Proctocort) administered rectally was assessed in healthy volunteers and patients with ulcerative colitis or X-irradiation colitis. Endogenous production of hydrocortisone was suppressed by dexamethasone. Comparison of these data with those obtained after intravenous administration enabled assessment of absolute bioavailability, which was 30.0 +/- 15.1% in healthy volunteers vs. 16.4 +/- 14.8% in patients (P = 0.09). Maximal concentrations of hydrocortisone were also decreased in patients, 277 +/- 215 nmol/L vs. 610 +/- 334 nmol/L (P = 0.03). There was a nonsignificant tendency to faster absorption of hydrocortisone in patients vs. healthy volunteers, as the times to peak concentration were, respectively, 2.5 +/- 1.2 h vs. 2.8 +/- 0.8 h (P = 0.64), and the mean absorption times were 1.96 +/- 1.45 h vs. 2.54 +/- 1.62 h (P = 0.46). Thus, rectal inflammation resulted in a lower absorption of hydrocortisone. In addition systemic plasma levels remained in the physiological range, so that only minor side effects are to be expected. PMID- 1600052 TI - The effects of lansoprazole, a new H+,K(+)-ATPase inhibitor, on gastric pH and serum gastrin. AB - This study examined the effects of dose and time of administration of lansoprazole on gastric pH and serum gastrin in healthy male volunteers. Three groups of six subjects received 10, 20 or 60 mg doses of lansoprazole or placebo. Doses were administered at 22.00 hours daily for 7 days. An additional 18 subjects received once daily 30 mg oral doses of lansoprazole or placebo; these subjects were dosed at either 08.00 hours or 22.00 hours in a randomized, crossover fashion with a 2-week washout period. Gastric pH was monitored for 24 h following the first and final dose, and 1 week following the completion of dosing. Lansoprazole, at all doses except 20 mg/day, significantly increased the median 24-hour gastric pH following 7 days of dosing (P less than 0.05). In addition, morning dosing in the 30-mg crossover group led to a higher 24-h median pH than evening dosing (P = 0.003). There was no difference in night-time median pH between morning and evening dosing. Morning dosing also led to a significant increase in gastric pH on study Day 1 (P less than 0.05). Plasma concentrations of lansoprazole were highly variable between subjects, but there was a significant correlation between AUC and the median 24-h gastric pH. Plasma concentrations and AUCs were higher on Day 7 than on Day 1 for subjects receiving 10 or 20 mg, but not for those receiving 30 or 60 mg doses. Lansoprazole bioavailability demonstrated a circadian effect manifested by higher plasma concentrations following morning dosing. Serum gastrin concentrations were elevated in all active medication groups. PMID- 1600053 TI - Effects of oral pantoprazole on 24-hour intragastric acidity and plasma gastrin profiles. AB - Pantoprazole selectively blocks gastric parietal cell H+,K(+)-ATPase. To define a dosage regimen for clinical trials we compared the effect of pantoprazole 40 and 60 mg daily on 24-h intragastric acidity and plasma gastrin concentrations using a double-blind, randomized, cross-over design. Eleven men took each of the three regimens (placebo, 40, 60 mg) for 5 days. On Day 5, 24-h pHmetry and plasma gastrin profile were performed. A consistent decrease in intragastric acidity with each dosage regimen was shown by a rise in 24-h median pH from 1.4 (1.2-1.8, IQR) on placebo to 2.3 (1.8-4.4, P = 0.0022) during pantoprazole 40 mg and to 3.5 (2.6-4.9, P = 0.0017) during 60 mg. Pantoprazole 40 and 60 mg maintained the intragastric pH above 3 for 33% and 58% of time, respectively, compared with 15% time with placebo. Twenty-four-hour integrated plasma gastrin concentration rose from 478 to 1798 and 1962 pmol.h/L, respectively. The drug was well tolerated. The decrease of acidity was dose related and should result in clinical efficacy similar to other antisecretory drugs. It is not known whether higher doses might abolish acid secretion. The optimal dose of pantoprazole is yet to be established. PMID- 1600054 TI - Night-time or morning dosing with H2-receptor antagonists: studies on acid inhibition in normal subjects. AB - H2-receptor antagonists are conventionally given at night. However, it remains unproven whether this regimen affords superior acid inhibition or healing rates for patients with duodenal ulcers compared to morning dosing. We have therefore examined the acid inhibitory effect of 300 mg ranitidine at night compared to 300 mg ranitidine in the morning in 8 normal male subjects. Intragastric acidity was measured by the radiotelemetry method and acid inhibition calculated from the percentage decrease in the area under the curve for hydrogen ion activity against time. Night-time ranitidine resulted in a significantly better (P less than 0.02) decrease of intragastric acidity than the same dose given in the morning (66.8 (61.8-77.6)% vs. 34 (15.5-49.1)%). This difference was found to be due to the fact that morning ranitidine inhibited gastric acid secretion when the intragastric acidity was already buffered by food. These data support the superiority of nocturnal dosing with H2-antagonists. PMID- 1600055 TI - Short report: twenty-four-hour hyperpepsinogenaemia in Helicobacter pylori positive subjects is abolished by eradication of the infection. AB - Twenty-four-hour plasma pepsinogen I and II concentrations were determined in 8 healthy subjects with antibody to Helicobacter pylori, before and after treatment with tripotassium dicitrato bismuthate, amoxycillin and metronidazole, Therapy was successful in the 5 subjects with active H. pylori infection. In these subjects, median integrated 24-h plasma pepsinogen I and II concentrations significantly decreased from 2288 and 357 micrograms.h/L before treatment, respectively, to 1811 and 171 micrograms.h/L at 4-6 weeks after treatment, and 1643 and 150 micrograms.h/L at 20-24 weeks. By contrast, in the 3 subjects without evidence of active H. pylori infection, pre-treatment plasma pepsinogen I and II concentrations were similar to values found in the H. pylori-infected subjects after successful therapy, and they did not change significantly in response to therapy. H. pylori infection is associated with reversible hyperpepsinogenaemia. PMID- 1600056 TI - Disposition of bismuth and renal function. PMID- 1600057 TI - [Opinions: the doctor/patient relation]. PMID- 1600058 TI - [Pregnancy in adolescence]. PMID- 1600059 TI - [Intervention against tobacco dependence in primary care. A study of 4 modalities of action]. AB - OBJECTIVE: To study the feasibility and evaluate the outcome over a years of four methods of combatting tobacco addiction at the primary care level: one directed towards the team's staff and three aimed at patients (counselling of smokers and specific treatment with nicotine chewing-gum and group or individual support). To compare the results of group and individual support. DESIGN: Uncontrolled intervention study. SITE. Primary care. PATIENTS AND OTHER PARTICIPANTS: 19 members of the Team. 121 smoking patients who attended for consultation. 62 people who requested treatment. INTERVENTIONS: Consensus on the attitude taken to tobacco within the team. Systematic counselling to smokers. Treatment with nicotine chewing-gum and group or individual support. MAIN MEASUREMENTS AND RESULTS: Numbers of people who gave up after a year: among the 12 smokers in the team, 4 (33%); 8 out of the 103 people who received counselling (7.7%) (Cl 2.60 12.94%); zero out of the 20 people who never attended for treatment or left the course after the first interview; zero out of the 20 treated in a group; and 8 out of the 20 treated individually (40%) (Cl 18.53-61.47%, p less than 0.001 regarding the treatment in group). CONCLUSIONS: The results support the effectiveness of three of the methods of intervention at the Primary Care level: intervention within the team itself, systematic counselling to smokers and treatment using nicotine chewing-gum and individual support. Group support must be reserved for staff with a specific training on Tobacco Addiction and the dynamics of group treatment. PMID- 1600060 TI - [The attitudes of primary care physicians towards the opening of health centers]. AB - OBJECTIVE: To measure doctors' attitudes to the opening of Health Centres. DESIGN: Descriptive study. SITE. Primary Care services on the island of Gran Canaria. PARTICIPANTS: Doctors with tenure. MAIN MEASUREMENTS AND RESULTS: From a self-administered Likert type questionnaire, it could be observed that the proportion of those polled who did not reply was linked to the number who had a "Fiscal Licence" (Odds Ratio O.R. = 6.26), a ratio which did not disappear when stratified by age (O.R. = 5.88 for those less than or equal to 40 and O.R. = 3.08 for those greater than 40). The scale presented high internal consistency (Cronbach alpha 0.937), indicating favorable attitudes from doctors integrated into Health Centres and both positive and negative attitudes in doctors of a traditional cut. Those specialising in Family Medicine, those under 40 years old, those who had no other health job and those connected with Trades Unions showed more favorable attitudes. CONCLUSIONS: Individual and group characteristics are linked to different attitudes. The knowledge, evaluation and behaviour components of doctor's attitudes must be improved, by involving the reference groups of both individuals and groups. PMID- 1600061 TI - [An evaluation of the prior appointment program in primary care by a user opinion survey]. AB - OBJECTIVE: To assess user-satisfaction on the introduction of an Appointments Scheme. DESIGN: Crossover and observational, with a random sample. SITE. 47?97 Health Centres and 72 Clinics in the Community of Valencia. PATIENTS AND OTHERS PARTICIPANTS: A random sample of 400 users. MAIN MEASUREMENTS AND RESULTS: A month after the introduction of the scheme, a survey was administered by staff of the centres themselves to a sample of users coming out from consulting rooms. The percentage of users who waited less than 15 minutes to see their doctor increased from 18% to 75.5% after the introduction of the Scheme. The average number of people in the waiting-rooms decreased from 61 to 14. 72.5% of users considered that the quality of health care received had improved. CONCLUSIONS: The users' evaluation of the programme is satisfactory. There was moreover a significant difference in favour of Health Centres as to fewer crowds in waiting-rooms, greater access to telephones, the evaluation of the quality of care and the average time of a consultation. PMID- 1600062 TI - [The degree of participation in a family planning survey performed by personal interview]. AB - OBJECTIVE: To analyse participation levels in a family planning survey. DESIGN: Descriptive and sectorial survey by means of personal interviews. SITE. Primary Care. Rural Context. Basic Health Area of Sanlucar la Mayor (Sevilla). PARTICIPANTS: 271 women of child-bearing age (15 to 49) chosen at random from the Municipal Census, who were invited by letter to the place of work of those doing the survey. INTERVENTIONS: Those who did not attend were invited on two further occasions. MAIN MEASUREMENTS AND RESULTS: The level of reply was 24.8% of those invited by the first letter, 25.12% by the second and 28.9% by the third. 40% of the total number did not attend on any of the three occasions: in 29.9% of cases because of work or study; in 22.9% because they hadn't received the letter; in 18.1% because of another commitment; in 26.5% due to lack of interest; 6% due to absence; and 3.6% owing to other reasons. 72.3% had no School Graduation Certificate. Only 10.3% were working. Differences of age, level of studies achieved and work activity between those attending and those not attending were considered significant but of no overall relevance. CONCLUSIONS: A survey based on personal interviews is a useful and valid way of collecting information in a rural community. Poor participation is thought to be due to both the low social and cultural levels and to the survey's subjects-matter. We consider that sending follow-up letters of invitation is a sound method of reducing as much as possible the number of home interviews which would otherwise have to be administered to those who did not attend. PMID- 1600063 TI - [Family planning: an evaluation of the program at a health center (1986-1990)]. AB - OBJECTIVE: To gain dome idea of the characteristics of the population attended at a Family Planning Clinic (FPC) in a Health Centre, attempting to find the coverage and performance of the Clinic. DESIGN: Retrospective descriptive study, which analysed 403 cases between July 1986 and December 1990. SITE. Family Planning Clinic in the "Huerta de la Reina" Health Centre. PATIENTS AND OTHERS PARTICIPANTS: Women of child-bearing age who requested a consultation during the period of the study. MAIN MEASUREMENTS AND RESULTS: A uni/bivariate analysis of the studies was carried out. Coverage of 16.3% of the population of child-bearing age, with 69.5% of the women being under 29, was attained. The most frequent motive for a consultation was advice on methods of contraception. Oral contraception (65.0%) was the most common form prescribed. 27.1% of those attending consultation were referred to the second level. Attendance at periodic check-ups was very low. PMID- 1600065 TI - [The secondary prevention of the cerebrovascular attack]. PMID- 1600064 TI - [Naproxen sodium in the treatment of otitis]. AB - OBJECTIVE: To assess the analgesic and anti-inflammatory value of sodium Naproxen in the treatment of otitis. DESIGN: A prospective study. There were interventions, but no controls. There was not a random distribution of the sample. SITE. Outpatient clinics in a Santander hospital. PATIENTS AND OTHER PARTICIPANTS: Patients presenting symptoms of acute or chronic otitis. INTERVENTIONS: A group of 20 patients with acute otitis and a second group of 15 with chronic otitis were treated normally; while 20 other patients suffering acute otitis and 17 with chronic otitis received in addition to normal treatment 550 mg of sodium naproxen every 12 hours. MAIN MEASUREMENTS AND RESULTS: The evolution of the clinical description was evaluated along the following parameters: perforation of the tympanum, otorrhea, pain, vertigo, migraines, hypoacusis and audiometries in acute cases of otitis; and all these and also tympanic biopsy in chronic cases. The results obtained indicated a statistically significant anatomical-pathological improvement in chronic cases of otitis treated with sodium naproxen; whereas in cases of acute otitis, these differences were observed in parameters such as hypoacusis, tympanometry, perforation of the tympanum and effectiveness of and tolerance towards additional treatment with sodium Naproxen. CONCLUSIONS: On the basis of the study's results as well as the high level of tolerance and absence of undesirable effects, we made a positive evaluation of the introduction of the aforesaid anti-inflammatory into the normal treatment of cases of otitis. PMID- 1600067 TI - [The paradoxes and possibilities of community participation in primary health care (I). The historical and conceptual problems]. PMID- 1600066 TI - [Adolescent medicine (I)]. PMID- 1600068 TI - [Familial colonic cancer]. PMID- 1600069 TI - [Antibiotic prescription at a health center: a descriptive study]. PMID- 1600070 TI - [Changes in taste due to captopril]. PMID- 1600071 TI - [The prescription of almagate as an indicator of quality in medical performance]. PMID- 1600072 TI - [Familial Gilbert's syndrome]. PMID- 1600073 TI - Sodium-23 and potassium-39 nuclear magnetic resonance relaxation in eye lens. Examples of quadrupole ion magnetic relaxation in a crowded protein environment. AB - Single and multiple quantum nuclear magnetic resonance (NMR) spectroscopic techniques were used to investigate the motional dynamics of sodium and potassium ions in concentrated protein solution, represented in this study by cortical and nuclear bovine lens tissue homogenates. Both ions displayed homogeneous biexponential magnetic relaxation behavior. Furthermore, the NMR relaxation behavior of these ions in lens homogenates was consistent either with a model that assumed the occurrence of two predominant ionic populations, "free" and "bound," in fast exchange with each other or with a model that assumed an asymmetric Gaussian distribution of correlation times. Regardless of the model employed, both ions were found to occur in a predominantly "free" or "unbound" rapidly reorienting state. The fraction of "bound" 23Na+, assuming a discrete two site model, was approximately 0.006 and 0.017 for cortical and nuclear homogenates, respectively. Corresponding values for 39K+ were 0.003 and 0.007, respectively. Estimated values for the fraction of "bound" 23Na+ or 39K+ obtained from the distribution model (tau C greater than omega L-1) were less than or equal to 0.05 for all cases examined. The correlation times of the "bound" ions, derived using either a two-site or distribution model, yielded values that were at least one order of magnitude smaller than the reorientational motion of the constituent lens proteins. This observation implies that the apparent correlation time for ion binding is dominated by processes other than protein reorientational motion, most likely fast exchange between "free" and "bound" environments. The results of NMR visibility studies were consistent with the above findings, in agreement with other studies performed by non-NMR methods. These studies, in combination with those presented in the literature, suggest that the most likely role for sodium and potassium ions in the lens appears to be the regulation of cell volume by affecting the intralenticular water chemical potential. PMID- 1600075 TI - Spontaneous oscillation of tension and sarcomere length in skeletal myofibrils. Microscopic measurement and analysis. AB - We have devised a simple method for measuring tension development of single myofibrils by micromanipulation with a pair of glass micro-needles. The tension was estimated from the deflection of a flexible needle under an inverted phase contrast microscope equipped with an image processor, so that the tension development is always accompanied by the shortening of the myofibril (auxotonic condition) in the present setup. The advantage of this method is that the measurement of tension (1/30 s for time resolution and about 0.05 micrograms for accuracy of tension measurement; 0.05 microns as a spatial resolution for displacement of the micro-needle) and the observation of sarcomere structure are possible at the same time, and the technique to hold myofibrils, even single myofibrils, is very simple. This method has been applied to study the tension development of glycerinated skeletal myofibrils under the condition where spontaneous oscillation of sarcomeres is induced, i.e., the coexistence of MgATP, MgADP and inorganic phosphate without free Ca2+. Under this condition, we found that the tension of myofibrils spontaneously oscillates accompanied by the oscillation of sarcomere length with a main period of a few seconds; the period was lengthened and shortened with stretch and release of myofibrils. A possible mechanism of the oscillation is discussed. PMID- 1600076 TI - Electrostatics of membrane adhesion. AB - We consider electrical double layer interaction under the conditions typically encountered during membrane fusion. Within the physiological concentration range of monovalent electrolytes the interaction is repulsive and the Poisson-Boltzmann calculation may be used to evaluate the force. When divalent counterions are added, strong ion-ion correlations make the Poisson-Boltzmann approximation inapplicable. We use the anisotropic hypernetted chain method to show that in the presence of small amounts of divalent counterions in adsorption equilibrium with the surfaces, the double layer interaction turns into attraction. This attractive electrostatic force may be the balancing contribution controlling membrane adhesion. PMID- 1600074 TI - Regulation of tension development by MgADP and Pi without Ca2+. Role in spontaneous tension oscillation of skeletal muscle. AB - The length of sarcomeres in isolated myofibrils fixed at both ends spontaneously oscillates when MgADP and Pi coexist with MgATP in the absence of Ca2+ (Okamura, N., and S. Ishiwata, 1988. J. Muscle Res. Cell. Motil. 9:111-119). Here, we report that MgADP and Pi function as an activator and an inhibitor, respectively, of tension development of single skeletal muscle fibers in the absence of Ca2+ and the coexistence of MgADP and Pi with MgATP induces spontaneous tension oscillation. First, the isometric tension sharply increased when the concentration of MgADP became higher than approximately 3x that of MgATP and saturated at approximately 90% of the tension obtained under full Ca2+ activation; in parallel with this sigmoidal increase of tension, MgATPase activity appeared. The inhibition of contraction by the regulatory system seems to be desuppressed by the allosteric effect of actomyosin-ADP complex, similarly to so-called rigor complex. The ADP-induced tension was decreased along a reversed sigmoidal curve by the addition of Pi; actomyosin-ADP-Pi complex, which has no desuppression function, may be formed by exogenous Pi; accompanying the decline of tension, spontaneous oscillations of tension and sarcomere length appeared. It is suggested that the length oscillation of each (half) sarcomere would occur through the transition of cross-bridges between force-generating (on) and non-force-generating (off) states, which may be regulated by the mechanical states (strain) of cross-bridges and/or thin filaments. PMID- 1600077 TI - A reconstruction of charge movement during the action potential in frog skeletal muscle. AB - The transfer of intramembrane charge during an action potential at 4 degrees C was reconstructed for a model representing the electrical properties of frog skeletal muscle by a cylindrical surface membrane and 16 concentric annuli ("shells") of transverse tubular membrane of equal radial thickness. The lumina of the transverse tubules were separated from extracellular fluid by a fixed series resistance. The quantity, geometrical distribution and steady-state and kinetic properties of charge movement components were described by equations incorporating earlier experimental results. Introducing such nonlinear charge into the distributed model for muscle membrane diminished the maximum amplitude of the action potential within the transverse tubules by 2 mV but increased the maximum size of the after-depolarization by 3-5 mV and also its duration. However, these changes were small in comparison to the 135-mV deflection represented by the action potential. They therefore did not justify altering the values of the electrical parameters adopted by Adrian R.H., and L.D. Peachey (1973. J. Physiol. [Lond.]. 235:103-131.) and used in the present calculations. Cable properties significantly affected the time course and extent of charge movement in each shell during action potential propagation into the tubular system. Q beta charge moved relatively rapidly in all annuli, and did so without significant latency (approximately 0.3 ms) after the surface action potential upstroke. Its peak displacement varied between 53 and 58% (the range representing the difference fiber edge/fiber axis) of the total Q beta charge. This was attained at 5.4-7.3 ms after the stimulus, depending on depth within the tubules. In contrast, q gamma moved after a 1.7-2.9 ms latency and achieved a peak displacement of up to 22-34% of available charge. Both charge movement species could be driven by repetitive (47.7 Hz) action potentials without buildup of charge transfer. Such stimulus frequencies would normally cause tetanus. Latencies in q gamma charge movement in response to an action potential were resolved into (a) propagation of tubular depolarization required to gain the "threshold" of q gamma charge (0.8-1.5 ms) and (b) dielectric loss processes. The latter took consistently around 1.5 ms throughout the tubular system. Taken with (c) the earlier reports of a minimal latency in delta [Ca2+] signals attributed to tubulo-cisternal coupling following voltage sensing (approximately 2 ms: Zhu, P.H., I. Parker, and R. Miledi., 1986. Proc. R. Soc. Lond. B. Biol. Sci. 229:39 46.). these times can be reconciled to the latency (~ 4-5 ms) reported between the onset of the surface action potential and that of delta [Ca2+] signals (Vergara, J., and M. Delay. 1986. Proc. R. Soc. Lond. B. Biol. Sci. 229:97-110.). This is consistent with a relationship between the q gamma system and excitation contraction coupling whether as an independent event (e.g.,Adrian, R.H., and C.L. H. Huang. 1984. J. Physiol. (Lond.). 353:419-434.) or as an end reaction following earlier (q beta) transfers of charge (e.g., Horowicz, P., and M.F. Schneider. 1981. J. Physiol. (Lond.). 314:565-593.; Melzer, W., M.F. Schneider, B.J. Simon,and G. Szucs. 1986. J. Physiol. (Lond.). 373:481-512.) PMID- 1600078 TI - Electrophysiological interaction through the interstitial space between adjacent unmyelinated parallel fibers. AB - The influence of interstitial or extracellular potentials on propagation usually has been ignored, often through assuming these potentials to be insignificantly different from zero, presumably because both measurements and calculations become much more complex when interstitial interactions are included. This study arose primarily from an interest in cardiac muscle, where it has been well established that substantial interstitial potentials occur in tightly packed structures, e.g., tens of millivolts within the ventricular wall. We analyzed the electrophysiological interaction between two adjacent unmyelinated fibers within a restricted extracellular space. Numerical evaluations made use of two linked core-conductor models and Hodgkin-Huxley membrane properties. Changes in transmembrane potentials induced in the second fiber ranged from nonexistent with large intervening volumes to large enough to initiate excitation when fibers were coupled by interstitial currents through a small interstitial space. With equal interstitial and intracellular longitudinal conductivities and close coupling, the interaction was large enough (induced Vm approximately 20 mV peak-to-peak) that action potentials from one fiber initiated excitation in the other, for the 40-microns radius evaluated. With close coupling but no change in structure, propagation velocity in the first fiber varied from 1.66 mm/ms (when both fibers were simultaneously stimulated) to 2.84 mm/ms (when the second fiber remained passive). Although normal propagation through interstitial interaction is unlikely, the magnitudes of the electrotonic interactions were large and may have a substantial modulating effect on function. PMID- 1600079 TI - Combined influence of cholesterol and synthetic amphiphillic peptides upon bilayer thickness in model membranes. AB - Deuterium (2H) NMR was used to study bilayer hydrophobic thickness and mechanical properties when cholesterol and/or synthetic amphiphillic polypeptides were added to deuterated POPC lipid bilayer membranes in the liquid-crystalline (fluid) phase. Smoothed acyl chain orientational order profiles were used to calculate bilayer hydrophobic thickness. Addition of 30 mol% cholesterol to POPC at 25 degrees C increased the bilayer thickness from 2.58 to 2.99 nm. The peptides were chosen to span the bilayers with more or less mismatch between the hydrophobic peptide length and membrane hydrophobic thickness. The average thickness of the pure lipid bilayers was significantly perturbed upon addition of peptide only in cases of large mismatch, being increased (decreased) when the peptide hydrophobic length was greater (less) than that of the pure bilayer, consistent with the "mattress" model of protein lipid interactions (Mouritsen, O.G., and M. Bloom. 1984. Biophys. J. 46:141-153). The experimental results were also used to examine the combined influence of the polypeptides and cholesterol on the orientational order profile and thickness expansivity of the membranes. A detailed model for the spatial distribution of POPC and cholesterol molecules in the bilayers was proposed to reconcile the general features of these measurements with micromechanical measurements of area expansivity in closely related systems. Experiments to test the model were proposed. PMID- 1600080 TI - In vivo study of chloroplast volume regulation. AB - This paper describes a new technique that can be used to study chloroplast volume regulation in vivo. Nuclear magnetic resonance spectroscopy was used to measure relative amounts of chloroplast water in Acer platanoides leaves as they dried in air, and also in leaf disks exposed to aqueous polyethylene glycol, sucrose, or glycerol. The chloroplasts retained a constant quantity of water as leaf water potentials varied between -0.05 and -1.90 MPa, indicating that volume regulation was effective throughout this range. The chloroplasts lost water when the water potential fell below -1.90 MPa, except when leaf disks were exposed to glycerol, suggesting that the lower limit of effective volume regulation is determined by physiological levels of osmotic solutes and that glycerol can be used for chloroplast osmoregulation. PMID- 1600081 TI - Membrane dipole potentials, hydration forces, and the ordering of water at membrane surfaces. AB - We have compared hydration forces, electrical dipole potentials, and structural parameters of dispersions of dipalmitoylphosphatidylcholine (DPPC) and dihexadecylphosphatidylcholine (DHPC) to evaluate the influence of fatty acid carbonyl groups on phospholipid bilayers. NMR and x-ray investigations performed over a wide range of water concentrations in the samples show, that in the liquid crystalline lamellar phase, the presence of carbonyl groups is not essential for lipid structure and hydration. Within experimental error, the two lipids have identical repulsive hydration forces between their bilayers. The higher transport rate of the negatively charged tetraphenylboron over the positively charged tetraphenylarsonium indicates that the dipole potential is positive inside the membranes of both lipids. However, the lack of fatty acid carbonyl groups in the ether lipid DHPC decreased the potential by (118 +/- 15) mV. By considering the sign of the potential and the orientation of carbonyl groups and headgroups, we conclude that the first layer of water molecules at the lipid water interface makes a major contribution to the dipole potential. PMID- 1600083 TI - Diffuse x-ray scattering from tropomyosin crystals. AB - Diffuse scattering analyses are emerging as a technique to extract additional dynamic information from x-ray diffraction data. In fact, when examined carefully, most protein crystals show significant diffuse scattering in addition to the usual Bragg diffraction. This diffuse scattering contains information about the disorder in the crystal that cannot be obtained from the Bragg diffraction data. Diffraction from tropomyosin crystals shows characteristic diffuse scattering streaks that are directly related to motion of the molecules. The structure of tropomyosin to 15 A resolution shows that the limited molecular contacts between molecules allow large conformational fluctuations of up to 8 A amplitude. Models for the three-dimensional motion of tropomyosin have been tested by comparing their predicted diffuse scattering patterns with the experimental data. From the parameters of the successful simulations, we were able to determine the amplitudes, directions, and distances over which the atomic displacements are correlated. PMID- 1600082 TI - Bilayer structure and physical dynamics of the cytochrome b5 dimyristoylphosphatidylcholine interaction. AB - Cytochrome b5 is a microsomal membrane protein which provides reducing potential to delta 5-, delta 6-, and delta 9-fatty acid desaturases through its interaction with cytochrome b5 reductase. Low angle x-ray diffraction has been used to determine the structure of an asymmetrically reconstituted cytochrome b5:DMPC model membrane system. Differential scanning calorimetry and fluorescence anisotropy studies were performed to examine the bilayer physical dynamics of this reconstituted system. These latter studies allow us to constrain structural models to those which are consistent with physical dynamics data. Additionally, because the nonpolar peptide secondary structure remains unclear, we tested the sensitivity of our model to different nonpolar peptide domain configurations. In this modeling approach, the nonpolar peptide moiety was arranged in the membrane to meet such chemically determined criteria as protease susceptibility of carboxyl- and amino-termini, tyrosine availability for pH titration and tryptophan 109 location, et cetera. In these studies, we have obtained a reconstituted cytochrome b5:DMPC bilayer structure at approximately 6.3 A resolution and conclude that the nonpolar peptide does not penetrate beyond the bilayer midplane. Structural correlations with calorimetry, fluorescence anisotropy and acyl chain packing data suggest that asymmetric cytochrome b5 incorporation into the bilayer increases acyl chain order. Additionally, we suggest that the heme peptide:bilayer interaction facilitates a discreet heme peptide orientation which would be dependent upon phospholipid headgroup composition. PMID- 1600084 TI - Calorimetric and x-ray diffraction studies of rye glucocerebroside mesomorphism. AB - Glucocerebrosides (GlcCer) isolated from the leaves of winter rye (Secale cereale L. cv Puma) differ from the more commonly investigated natural and synthetic cerebrosides, in that greater than 95% of the fatty acids are saturated and monounsaturated hydroxy fatty acids. Isomers of the trihydroxy long chain base hydroxysphingenine (t1(8:18 cis or trans)) and isomers of sphingadienine (d18:2(4trans, 8 cis or trans)) comprise 77% and 17%, respectively, of the total long chain bases. The phase behavior of fully hydrated and dry rye leaf GlcCer was investigated using differential scanning calorimetry (DSC) and x-ray diffraction. On initial heating, aqueous dispersions of GlcCer exhibit a single endothermic transition at 56 degrees C and have an enthalpy (delta H) of 46 J/g. Cooling to 0 degrees C is accompanied by a small exothermic transition (delta H = -8 J/g) at 8 degrees C. On immediate reheating, a broad exothermic transition (delta H = -39 J/g) is observed between 10 and 20 degrees C in addition to a transition at 56 degrees C. These transitions are not reversible, and the exothermic transition rapidly diminishes when the sample is held at low temperature. Using x-ray diffraction, it was determined that the endotherm at 56 degrees C represents a transition from a highly ordered lamellar crystalline phase (Lc) with a d-spacing of 57 A and a series of wide-angle reflections in the 3-10 A range, to a lamellar liquid crystalline (L alpha) phase having a d-spacing of 55 A and a diffuse wide-angle scattering peak centered at 4.7 A. Cooling leads to the formation of a metastable gel phase (L beta) with a d-spacing of 64.0 A and a single broad reflection at 4.28 A. Subsequent warming to above 15 degrees C restores the original Lc phase. Thus, rye GlcCer in excess water exhibit a series of irreversible transitions and gel phase metastability. Dry GlcCer undergo an initial heating endothermic transition at 130 degrees C, which is ascribed to a transformation into the HII phase from a two phase state characterized by the coexistence of phases with disordered (alpha) and helical (delta) type chain conformations but of unknown lattice identity: An exotherm at 67.5 degrees C observed upon subsequent cooling is of unknown origin. Since an undercooled HII phase persists down to 19 degrees C, the exotherm may derive in part from an alpha-to-delta type chain packing conformational change especially under slow cooling conditions. Upon reheating from low temperatures to 65 degrees C, a phase with a two-dimensional, primitive rectangular lattice and delta-like chain packing (R8 phase) in coexistence with the HI, phase emerges. With continued heating to 90 degrees C these coexisting phases give way to a phase with a two dimensional, centered rectangular lattice and delta-like chain packing (P8phase) which again coexists with the HI, phase. Above 130 degrees C, the Pb phase disappears and the sample converts completely to the HI, phase as observed upon initial heating. These results indicate that the mesomorphic behavior of rye leaf GIcCer is distinct from that of other cerebrosides. PMID- 1600086 TI - Frequency domain impedance measurements of erythrocytes. Constant phase angle impedance characteristics and a phase transition. AB - We report measurements of the electrical impedance of human erythrocytes in the frequency range from 1 Hz to 10 MHz, and for temperatures from 4 to 40 degrees C. In order to achieve high sensitivity in this frequency range, we embedded the cells in the pores of a filter, which constrains the current to pass through the cells in the pores. Based on the geometry of the cells embedded in the filter a circuit model is proposed for the cell-filter saline system. A constant phase angle (CPA) element, i.e., an impedance of the form Z = A/(j omega)alpha, where A is a constant, j = square root of -1, omega is angular frequency, and 0 less than alpha less than 1 has been used to describe the ac response of the interface between the cell surface and the electrolyte solution, i.e., the electrical double layer. The CPA and other elements of the circuit model are determined by a complex nonlinear least squares (CNLS) fit, which simultaneously fits the real and imaginary parts of the experimental data to the circuit model. The specific membrane capacitance is determined to be 0.901 +/- 0.036 microF/cm2, and the specific cytoplasm conductivity to be 0.413 +/- 0.031 S/m at 26 degrees C. The temperature dependence of the cytoplasm conductivity, membrane capacitance, and CPA element has been obtained. The membrane capacitance increases markedly at approximately 37 degrees C, which suggests a phase transition in the cell membrane. PMID- 1600085 TI - Temperature-reversible eruptions of vesicles in model membranes studied by NMR. AB - Deuterium (2H) and phosphorus (31P) nuclear magnetic resonance (NMR) and freeze fracture electron microscopy were used to study spontaneous vesiculation in model membranes composed of POPC:POPS with or without cholesterol. The NMR spectra indicated the presence of a central isotropic line, the intensity of which is reversibly and linearly dependent upon temperature in the L alpha phase, with no hysteresis when cycling between higher and lower temperatures. Freeze-fracture microscopy showed small, apparently connected vesicles that were only present when the samples were frozen (for freeze-fracture) from an initial temperature of 40-60 degrees C, and absent when the samples are frozen from an initial temperature of 20 degrees C. Analysis of motional narrowing was consistent with the isotropic lines being due to lateral diffusion in (and tumbling of) small vesicles (diameters approximately 50 nm). These results were interpreted in terms of current theories of shape fluctuations in large unilamellar vesicles which predict that small daughter vesicles may spontaneously "erupt" from larger parent vesicles in order to expel the excess area created by thermal expansion of the bilayer surface at constant volume. Assuming that all the increased area due to increasing temperature is associated with the isotropic lines, the NMR results allowed a novel estimate of the coefficient of area expansion alpha A in multilamellar vesicles (MLVs) which is in good agreement with micromechanical measurements upon giant unilamellar vesicles of similar composition. Experiments performed on unilamellar vesicles, which had been placed upon glass beads, confirmed that alpha A determined in this way is unchanged compared with the MLV case. Addition of the highly positively charged (extrinsic) myelin basic protein (MBP) to a POPC:POPS system showed that membrane eruptions of the type described here occur in response to the presence of this protein. PMID- 1600087 TI - Protein structures in SDS micelle-protein complexes. AB - Sodium dodecyl sulfate (SDS) is used more often than any other detergent as an excellent denaturing or "unfolding" detergent. However, formation of ordered structure (alpha-helix or beta-sheet) in certain peptides is known to be induced by interaction with SDS micelles. The SDS-induced structures formed by these peptides are amphiphilic, having both a hydrophobic and a hydrophilic face. Previous work in this area has revealed that SDS induces helical folding in a wide variety of non-helical proteins. Here, we describe the interaction of several structurally unrelated proteins with SDS micelles and the correlation of these structures to helical amphiphilic regions present in the primary sequence. It is likely that the ability of native nonordered protein structures to form induced amphiphilic ordered structures is rather common. PMID- 1600088 TI - Simulation of the role of water in ion channel gating. PMID- 1600089 TI - Protein structure prediction based on statistical potential. PMID- 1600091 TI - Application of site-directed mutagenesis in nuclear magnetic resonance spectroscopy. PMID- 1600090 TI - Analysis and refinement of criteria for predicting the structure and relative orientations of transmembranal helical domains. AB - We are interested in modeling the membrane-spanning domain of the serotonin 5 HT1A G-protein coupled receptor. This superfamily of proteins is predicted to share the topology of the seven transmembrane helices of bacteriorhodopsin (BR), even though no significant sequence homology had been identified. We found significant homologies by allowing for helix shuffling corresponding to minimal exon shuffling during evolution. Consequently, our strategy for building the model for the 5-HT1A receptor has been to construct hypotheses concerning helix helix interactions, their orientations, and arrangement in bundles surrounded by lipid, based on the 3.5 A resolution structure of BR. Inferences resulting from such models were tested against the 2.3 A resolution structure of the photosynthetic reaction center (PRC) from Rhodobacter Viridis. These comparisons led us to a reevaluation of current methods for the identification and topological orientation of membrane-embedded alpha-helices. We find that methods used currently in the construction of helical transmembrane domains could be misleading if used indiscriminately. These methods include the hydrophobicity profile, the hydrophobic moment, helix amphiphilicity, and charge neutralization. A refinement is proposed here, based on empirical observations, molecular modeling, and physicochemical considerations designed to overcome some of the shortcomings inherent in the use of the above mentioned methods. Here we present the analysis of two of the motifs identified in our study that led to the proposed refinements: the distribution of acidic and basic residues in the transmembranal domains, and the kink induced by a Pro residue in an alpha-helix. PMID- 1600092 TI - Structure and interactions of magainin antibiotic peptides in lipid bilayers: a solid-state nuclear magnetic resonance investigation. PMID- 1600093 TI - A single nonpolar residue in the deep pore of related K+ channels acts as a K+:Rb+ conductance switch. AB - K+ and Rb+ conductances (GK+ and GRb+) were investigated in two delayed rectifier K+ channels (Kv2.1 and Kv3.1) cloned from rat brain and a chimera (CHM) of the two channels formed by replacing the putative pore region of Kv2.1 with that of Kv3.1. CHM displayed ion conduction properties which resembled Kv3.1. In CHM, GK+ was three times greater than that of Kv2.1 and GRb+/GK+ = 0.3 (compared with 1.5 and 0.7, respectively, in Kv2.1 and Kv3.1). A point mutation in CHM L374V, which restored 374 to its Kv2.1 identity, switched the K+/Rb+ conductance profiles so that GK+ was reduced fourfold, GRb+ was increased twofold, and GRb+/GK+ = 2.8. Quantitative restoration of the Kv2.1 K+/Rb+ profiles, however, required simultaneous point mutations at three nonadjacent residues suggesting the possibility of interactions between residues within the pore. The importance of leucine at position 374 was verified when reciprocal changes in K+/Rb+ conductances were produced by the mutation of V374L in Kv2.1 (GK+ was increased threefold, GRb+ was decreased threefold, and GRb+/GK+ = 0.2). We conclude that position 374 is responsible for differences in GK+ and GRb+ between Kv2.1 and Kv3.1 and, given its location near residues critical for block by internal tetraethylammonium, may be part of a cation binding site deep within the pore. PMID- 1600095 TI - Is a beta-barrel model of the K+ channel energetically feasible? PMID- 1600094 TI - Gating currents in Shaker K+ channels. Implications for activation and inactivation models. AB - We have studied ionic and gating currents in mutant and wild-type Shaker K+ channels to investigate the mechanisms of channel activation and the relationship between the voltage sensor of the channel and its inactivation particle. The turn on of the gating current shows a rising phase, indicating that the hypothetical identical activation subunits are not independent. Hyperpolarizing prepulses indicate that most of the voltage-dependence occurs in the transitions between closed states. The open-to-closed transition is voltage independent, as suggested by the presence of a rising phase in the off gating currents. In Shaker channels showing fast inactivation, the off gating charge is partially immobilized as a result of depolarizing pulses that elicit inactivation. In mutant channels lacking inactivation, the charge is recovered quickly at the end of the pulse. Internal TEA mimics the inactivation particle in its behavior but the charge immobilization is established faster and is complete. We conclude that the activation mechanism cannot be due to the movement of identical independent gating subunits, each undergoing first order transitions, and that the inactivation particle is responsible for charge immobilization in this channel. PMID- 1600096 TI - Atomic scale structure and functional models of voltage-gated potassium channels. AB - Recent mutagenesis experiments have confirmed our hypothesis that a segment between S5 and S6 forms the ion selective portion of voltage-gated ion channels. Based on these and other new data, we have revised previous models of the general folding pattern of voltage-gated channel proteins and have developed atomic scale models of the entire transmembrane region of the Shaker A K+ channel. In these models, the ion selective region is a beta-barrel that spans the outer half of the membrane. The inner half of the pore is larger. The voltage-dependent conformational changes of activation gating are modeled to occur by the "helical screw" mechanism, in which the four S4 segments move along and rotate about their axes. These changes are followed by a voltage-independent conformational change, in which the segments linking S4 to S5 move from blocking the intracellular entrance of the pore to forming part of the lining of the large inner portion of the pore. The NH2-terminal of the protein was modeled as an alpha-helix that plugs the intracellular half of the pore to inactivate the channel. PMID- 1600097 TI - Intercellular communication through gap junctions is reduced in senescent cells. PMID- 1600098 TI - Membrane assembly of bacterio-opsin mutants expressed in halobacteria and incorporation of the proteins into phospholipid bilayers. PMID- 1600099 TI - Fourier transform infrared spectroscopic analysis of altered reaction pathways in site-directed mutants: the D212N mutant of bacteriorhodopsin expressed in Halobacterium halobium. PMID- 1600100 TI - Site-specific mutations of nicotinic acetylcholine receptor at the lipid-protein interface dramatically alter ion channel gating. PMID- 1600101 TI - Probing conformational changes in the nicotinic acetylcholine receptor by Fourier transform infrared difference spectroscopy. AB - We have developed a Fourier transform infrared (FTIR) difference method for probing conformational changes that occur upon the binding of ligands to the nicotinic acetylcholine receptor (nAChR). Our approach is to deposit reconstituted nAChR membranes in a thin film on the surface of a germanium internal reflection element, acquire FTIR spectra in the presence of bulk aqueous solution using attenuated total reflection, and then trigger conformational changes by sequentially flowing a buffer either with or without an agonist past the film surface. Using the fluorescent probe, ethidium bromide, it is demonstrated that the method of nAChR film deposition does not affect the ability of the receptor to undergo the resting-to-desensitized state transition. The difference of FTIR spectra of nAChR films recorded in the presence and absence of agonists reveal highly reproducible infrared bands that are not observed in the difference of spectra recorded with only buffer flowing past the film surface. Some of the bands are assigned to changes in protein secondary structure and to changes in the structure of individual amino acid residues. Bands arising from the vibrations of the agonist bound to the receptor are also observed. The results demonstrate that FTIR difference spectroscopy can detect structural changes in the nAChR that occur upon the binding of ligands. The technique will be an effective method for investigating nAChR structure and function as well as receptor-drug interactions. PMID- 1600102 TI - Bacterial chemoreceptor signaling probed by flash photorelease of a caged serine. AB - A caged serine, a photolabile compound that liberates serine upon photolysis, has been synthesized. Smooth-swimming responses of the bacterium Escherichia coli to caged serine photorelease were videotaped. The mean latency was measured from the videorecords using computerized motion analysis. This time was approximately 0.2 s. Caged photorelease of a photolabile but nonchemotactic serine analogue had no effect on the swimming behavior of the bacteria. A tumbly mutant strain lacking tsr, the serine chemoreceptor, did not respond to caged serine photorelease. PMID- 1600103 TI - Kinetic behavior of cloned mouse acetylcholine receptors. A semi-autonomous, stepwise model of gating. PMID- 1600104 TI - Steric factors limit access to the noncompetitive inhibitor site of the nicotinic acetylcholine receptor. Fluorescence studies. PMID- 1600105 TI - Biophysical studies of cytochromes B5 with amino acid substitutions in the membrane-binding domain. PMID- 1600106 TI - Multisite association by recombinant proteins can enhance binding selectivity. Preferential removal of immune complexes from serum by immobilized truncated FB analogues of the B domain from staphylococcal protein A. PMID- 1600107 TI - Analyzing the fusion process of influenza hemagglutinin by mutagenesis and molecular modeling. PMID- 1600108 TI - Exploration of the functional significance of the stilbene disulfonate binding site in mouse band 3 by site-directed mutagenesis. PMID- 1600109 TI - Pharmacodynamics as a tool to assess the bioequivalence of non-systemically available drugs: size of the sample required. AB - Bioequivalence studies of drugs which are not systematically available must rely on the measure of the pharmacological response. Detection of a difference between two such preparations is often hampered by the need to include an elevated number of subjects. The number of subjects can be reduced whenever: (a) the characteristics of the subjects are well defined, (b) the selection of the baseline target effect is done rigorously, (c) the target effect can be quantified reliably, (d) the effect is measured when less variability is expected, e.g. at steady state, (e) the effect is measured repeatedly, and (f) when possible, the predicted maximal effect (Emax) and the concentration to elicit 50% of Emax are estimated. A simple equation has been derived to estimate the number of subjects needed in these bioequivalence studies. PMID- 1600110 TI - In vitro reduction of rhein anthraquinone to rhein anthrone by rat cecal microflora and some intestinal bacterial strains. AB - After in vitro incubation of cecal content from CVL or gnotobiotic rats with rhein anthraquinone (1 mg g-1) for 18 h at 37 degrees, the anthraquinone was converted to rhein anthrone for 23.5 (SD +/- 3.4) per cent and 19.4 (+/- 4.7) per cent, respectively. Liquid cultures of some strictly anaerobic fecal bacteria of man and mouse incubated with rhein anthraquinone (62.5 micrograms ml-1) for 48 h at 37 degrees, revealed only small amounts of reduced substance. Although the underlying mechanisms of the differences in both conditions remain unclear, the experimental data accentuate the need for using cecal content when exploring the in vitro metabolism of anthranoids by the intestinal microflora. The conversion was chemically proven by derivatization of the anthrone with 4-nitroso-N-N dimethylaniline in pyridine, followed by hydrolysis and identification of the released anthranoid by mass spectrometry. The in vitro reduction capacity of the cecal content of CVL rats was drastically decreased by oral administration to rats of different combinations of neomycin sulfate, metronidazole, bacitracin and Na-penicillin G. In these cases the conversion ranked between 0.2 per cent and 5.2 per cent the first day after administration. It is concluded that rhein anthraquinone in cecal content is reduced to the highly reactive and labile rhein anthrone, which accounts for the in vivo disappearance of dihydroxy-anthranoid equivalents in routine analysis after oral administration of anthraquinones to experimental animals. PMID- 1600111 TI - Pharmacokinetics of ketotifen after oral administration to healthy male subjects. AB - The pharmacokinetics of 2 mg ketotifen from four different oral dosage forms were examined in two randomized, balanced cross-over studies. Forty healthy male subjects participated. Each of 20 subjects received two capsule formulations and each of the other 20 subjects received two syrup formulations. Ketotifen concentrations in plasma were determined by a modified GC-MS method. The limit of quantitation was 40 pg ml-1. Inter-day precision and accuracy calculated from quality control samples were 16.3 per cent (-1.9 per cent), 19.8 per cent (+4.5 per cent) and 23.6 per cent (+5.9 per cent) at plasma concentration levels of 86 (n = 18), 215 (n = 19) and 343 (n = 18) pg ml-1, respectively. Ketotifen was rapidly absorbed from all dosage forms reaching Cmax in the order of 400 pg ml-1 after the syrup formulations and 300 pg ml-1 after the capsule formulations within 2 to 4 h. The syrup formulations showed a significantly more rapid rate of absorption as assessed by Tmax. No significant differences in extent of absorption between dosage forms were observed. The terminal elimination half-life of ketotifen varied between subjects from 7 to 27 hours with a mean of about 12 h. The minor pharmacokinetic difference between dosage forms observed in this study is unlikely to be of clinical significance. PMID- 1600112 TI - A simplified approach for evaluation of hepatic drug-oxidizing activity with a simultaneous determination of caffeine and trimethadione and their demethylated metabolites in rats with a selective cytochrome P-450 inducer. AB - We determined the blood concentrations of caffeine (CA) and its three primary dimethylxanthine metabolites: theobromine (TB), paraxanthine (PX), and theophylline (TP), and trimethadione (TMO) and its demethylated metabolite dimethadione (DMO) after the simultaneous administration of CA (10 mg kg-1) and TMO (4 mg kg-1) to rats pretreated with phenobarbital (PB:40 and 80 mg kg-1 i.p. daily for 3 days) and 3-methylcholanthrene (MC: 10 and 20 mg kg-1 i.p. daily for 2 days). After the oral administration of CA and TMO, the PB-pretreated rats showed a significant increase in TMO metabolism, whereas the CA metabolism was greatly accelerated in rats pretreated with MC. In five pretreated groups, there were correlations which were determined 1 h after the administration of CA and TMO, between the plasma half-life (t1/2) of CA and the TB/CA, PX/CA, and TP/CA ratios. The coefficients of correlation (r) ranged from -0.881 to -0.908, and the coefficients of correlation between the CL of CA and the TB/CA, PX/CA, and TP/CA ratios ranged from 0.959 to 0.989. There were high correlations between the t1/2 of TMO and the DMO/TMO ratio at 1 h after administration with r = -0.966, and between the CL of TMO and the DMO/TMO ratio with r = 0.971. The above results suggest that one blood sampling after the simultaneous administration of CA and TMO enables prediction of the degree of each hepatic drug-oxidizing activity because the P-450 isozymes involved in metabolism of CA and TMO are different. PMID- 1600113 TI - Comparison of disposition behavior and de-coppering effect of triethylenetetramine in animal model for Wilson's disease (Long-Evans Cinnamon rat) with normal Wistar rat. AB - The disposition behaviors and de-coppering effect of triethylenetetramine dihydrochloride (trientine), a selective chelating agent for copper and an 'orphan drug' for Wilson's disease, have been evaluated in an animal model, Long Evans Cinnamon (LEC) rats, and normal rats (Wistar). In LEC rats, urinary excretion of trientine was remarkably lower than that of Wistar rats. The absorption rates from the jejunal loop and in vitro metabolism in the liver S9 fraction (supernatant of 9000 x g) were approximately the same for both strains. The decline of urinary excretion of trientine in LEC rats is thought to be due mainly to the lowering of the functional activity of the kidney, because urinary excretion of creatinine and phenolsulfonphthalein were significantly lower in LEC rats than those in Wistar rats. Both acceleration of urinary excretion of copper and reduction of hepatic copper levels were observed with treatment of trientine in LEC rats aged 6 weeks. In LEC rats aged 13 weeks, however, no de-coppering effect from the liver was observed, though urinary excretion of copper was increased. These results suggest that trientine has a pharmacological effect in disease state, especially in the early stages of hepatitis. PMID- 1600114 TI - Absorption and disposition of fluvastatin, an inhibitor of HMG-CoA reductase, in the rabbit. AB - The absorption and disposition of fluvastatin have been studied in the female rabbit. In naive rabbits receiving a single oral dose (1 mg kg-1) of [3H] fluvastatin, absorption was rapid and amounted to c. 90 per cent compared with an intravenous reference dose. The drug was subject to considerable first-pass effect, its absolute bioavailability being 46 per cent. The steady-state volume of distribution of fluvastatin was 0.29 +/- 0.04 l kg-1 while the total body clearance was 0.33 +/- 0.05 1 h-1 kg-1. The administered radioactivity was excreted predominantly in feces, with the renal pathway accounting for 28 +/- 4 per cent of the oral dose and 32 +/- 3 per cent of the intravenous dose. In pregnant rabbits on a multiple oral dosing regimen, 1 mg kg-1 day-1 beginning day 6 post-conception (p.c.), steady-state concentrations in maternal blood and tissues were achieved within 5 days. The concentrations in the reproductive organs were c. 25-50 per cent of that in maternal blood while those in the kidneys and liver were considerably higher. In contrast, radioactivity levels in the fetuses and amniotic fluid decreased significantly during repeated drug administration. The fetus: placenta and amniotic fluid: placenta concentration ratios declined from 0.92 and 0.97, respectively, on day 10 p.c. to 0.10 and 0.04, respectively, on day 18 p.c., indicating a limited transfer of fluvastatin and/or its metabolite(s) across the placenta at the later stage of pregnancy. After cessation of dosing, radioactivity levels in all tissues and fluids showed a progressive and nearly parallel decline, suggesting no tissue retention of the drug. PMID- 1600115 TI - Effect of basic drugs on the hepatic uptake of ouabain by sinusoidal plasma membrane vesicles isolated from rat liver. AB - Although antiarrhythmic drugs are used to treat digitalis-induced cardiac disorders, some of these drugs have been reported to increase the serum digoxin concentration in patients, causing the severe side-effects. We have previously shown that many basic drugs including antiarrhythmic drugs inhibited the hepatic uptake of cardiac glycosides into isolated rat hepatocytes, which could be a cause for the increased serum digoxin concentration. The present study was designed to examine the mechanism of this inhibition using isolated rat sinusoidal plasma membrane vesicles. The effect of nine basic drugs (dipyridamole, nifedipine, verapamil, chlorpromazine, lidocaine, quinidine, ajmaline, disopyramide, and propranolol) on the uptake of ouabain was studied. Quinidine reduced the initial uptake rate of ouabain (30 s) while it did not change the uptake of ouabain in an equilibrium condition (30 min). Other basic drugs, such as verapamil, dipyridamole, and nifedipine also significantly reduced the initial uptake rate of ouabain. These basic drugs had no effect on the membrane fluidity. The inhibitory effects on the vesicular uptake were significantly correlated with the inhibitory effects on ouabain uptake by the isolated rat hepatocytes. These findings may suggest that the mechanism of the inhibition involves the inhibition of the transport process via the sinusoidal plasma membrane. PMID- 1600116 TI - Pharmacokinetics of drugs in blood. VII: Unusual distribution and blood storage effect of vancomycin. PMID- 1600117 TI - The ASN today: the president's report. PMID- 1600119 TI - On the mechanisms of impaired phagocytosis in phosphate depletion. AB - Phosphate depletion (PD) impairs the phagocytic ability of polymorphonuclear leukocytes (PMNL). This derangement has been attributed to the low ATP content of PMNL in PD. The mechanisms responsible for the low ATP content are not well defined. Phosphorus deficiency, per se, and/or other cellular metabolic consequences of PD such as a rise in cytosolic calcium ([Ca2+]i) could be responsible. Indeed, PD is associated with a rise in [Ca2+]i in other cells, and such an event may inhibit mitochondrial ATP production. It is also not evident whether the impaired phagocytosis in PD is due to low ATP content and/or a rise in the [Ca2+]i of PMNL. The study presented here examined levels of [Ca2+]i, ATP content, and the phagocytic ability of PMNL from PD and pair-weighed (PW) rats and evaluated the potential beneficial effect of treatment with verapamil (V), which may prevent a rise in [Ca2+]i and the consequent effects on ATP content and the phagocytosis of PMNL. The resting levels of [Ca2+]i of PMNL from PD rats (148 +/- 3.9 nM) were significantly (P less than 0.01) higher, and the ATP contents (4.8 +/- 0.2 nmol/5 x 10(6) PMNL) were significantly (P less than 0.01) lower than in PW (111 +/- 2.8 nM and 9.3 +/- 0.3 nmol/5 x 10(6) PMNL), PW-V (114 +/- 2.2 nM and 9.3 +/- 0.28 nmol/5 x 10(6) PMNL), and PD-V (112 +/- 1.8 nM and 6.6 +/ 0.19 nmol/5 x 10(6) PMNL) animals. Despite the normal [Ca2+]i in the PMNL of PD V rats, their ATP contents were still significantly (P less than 0.01) lower than those of PW or PW-V rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600118 TI - Specialized collagen mRNA and secreted collagens in human glomerular epithelial, mesangial, and tubular cells. AB - Isolated glomeruli and cultured cells were examined under nonmitogenic conditions by Northern hybridization of steady-state mRNA levels for procollagens alpha 1(I), alpha 1(III), alpha 1(IV), alpha 2(IV), beta-actin, and fibronectin. Procollagens concurrently secreted from these cells were characterized after limited pepsin digestion. Poly(A)-mRNA from freshly isolated whole porcine glomeruli was primarily type IV. For cultured glomerular and tubular epithelial cells, the collagen mRNA species were almost exclusively alpha 1(IV) and alpha 2(IV). Correspondingly, the secreted collagen was almost entirely type IV. The mRNA signals for collagens in glomerular mesangial cells included alpha 1(I), alpha 1(IV), alpha 2(IV), and less alpha 1(III). The secreted collagens were also types I and IV, with less types III and V. There were similar patterns of mRNA signal levels for the two type IV collagens and similar patterns of expression of alpha 1(I) and alpha 1(III). In situ hybridization showed the fibroblast and epithelial cell populations homogeneous in expressing the same mRNA signals seen by Northern hybridization. These findings establish the correlation of collagen mRNA and protein expression of collagens in differentiated glomerular cells in culture, under resting nonmitotic conditions. PMID- 1600120 TI - Effects of hemodialysis on activation of lymphocytes: analysis by an in vitro dialysis model. AB - Patients undergoing maintenance hemodialysis have impaired immune responsiveness, which appears to deteriorate progressively with the duration of the replacement treatment. It has been suggested that it is caused by a chronic preactivation state of T cells caused by hemodialysis. Each treatment session has been compared with a recurring "acute-phase" inflammatory reaction. In this study, the acute effects of hemodialysis on the activation state and functional responsiveness of normal peripheral blood mononuclear cells have been evaluated by use of an in vitro dialysis model. The dialysis was carried out with either cuprophan or polysulfone membranes, with or without sodium acetate in the dialysis fluid. It was observed that a single session of in vitro dialysis did not induce production of interleukin-2 (IL-2) and did not alter the expression of IL-2 receptor (IL-2R) on the cytoplasmic membrane and the secretion of soluble IL-2R, whereas it induced transcription of mRNA for IL-2R. The proliferative response of lymphocytes to phytohemagglutinin or IL-2 in vitro also did not change after a single dialysis session. There was only a slight decrease of the release of soluble IL-2 receptor by phytohemagglutinin-stimulated cells after dialysis. Dialysis induced an active synthesis of IL-1 by peripheral blood mononuclear cells, even in the absence of sodium acetate in the dialysate bath, but there was no release of IL-1 to the circulating medium. The results show that a single dialysis encounter can acutely prime the activation of human peripheral blood mononuclear cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600121 TI - Pseudomonas exit site infections in continuous ambulatory peritoneal dialysis patients. AB - The purpose of this study is to examine the natural history of Pseudomonas aeruginosa exit site infections in continuous ambulatory peritoneal dialysis (CAPD) patients treated with oral ciprofloxacin and local exit site care. A retrospective view was undertaken of 18 episodes of P. aeruginosa exit site infections developing in 17 patients maintained on CAPD during 1989 and 1990. Standardized therapy for the exit site infection consisted of oral ciprofloxacin (500 mg twice daily) and local exit site care with antiseptic agents. Fifteen (83%) of 18 of the pseudomonas exit site infections resolved with therapy. Three episodes (17%) required catheter removal to successfully eradicate the infection. Four of the 15 patients whose exit site infections resolved developed P. aeruginosa peritonitis 2 to 9 months after the clinical resolution of the exit site infection. The majority of pseudomonas exit site infections in CAPD patients can be successfully treated with oral ciprofloxacin and local care. Approximately 17% of the patients in this study required catheter removal to successfully eradicate the infection and an additional 22% of the patients developed pseudomonas peritonitis several months after the resolution of the exit site infection. PMID- 1600122 TI - Rate of change of end-stage renal disease treatment incidence 1978-1987--has there been selection? AB - End-stage renal disease (ESRD) treatment rates in the United States have increased steadily since 1973. Decreasing selection against elderly patients with a poor prognostic primary cause of ESRD (i.e., diabetic nephropathy) may partly account for this increase in rates. To test this hypothesis, we calculated log ESRD treatment incidence (ESRDI) rates by four major primary causes of ESRD (diabetic nephropathy (DN), hypertensive nephropathy (HN), glomerulonephritis (GN), and cystic kidney disease (PC); two age groups (old (O), greater than 65 and young (Y), 15 to 44 yr of age) for black and white, male and female, new ESRD patients from 1978 to 1987. As predicted, summary log ESRDI slopes (produced by analysis of covariance) occurred in the following decreasing order, ODN (0.19), OGN = OHN = YDN (0.134). YHN = YPC = YGN (in white patients) = slope not significantly different from 0. Log ESRDI slopes for young black males and females with GN increased significantly between 1978 and 1987, possibly as a result of an increased incidence of GN. In conclusion, decreasing selection may be a factor in the continuing increase in the U.S. ESRD population. PMID- 1600123 TI - Basolateral transport of tetraethylammonium by a clone of LLC-PK1 cells. AB - In these studies, a clone of cells derived from the porcine renal epithelial line LLC-PK1 grown on porous filters was used to evaluate basolateral uptake of the organic cation tetraethylammonium (TEA). (3H) TEA (1 microM) entered cells in a saturable and time-dependent manner achieving a steady-state value at 2 to 2.5 h. Uptake was reduced by hypothermia and the metabolic inhibitors sodium azide and iodoacetate. Several other organic cations in 1 mM concentrations inhibited the majority of TEA uptake. In lower concentrations, the inhibitory potency of these was: verapamil greater than cimetidine approximately amiloride approximately quinidine greater than procainamide approximately N1-methylnicotinamide. When sodium was replaced with potassium in the uptake medium, TEA uptake was also reduced consistent with electrogenic transport. However, uptake was reduced further by 1 mM cimetidine in the presence of both NaCl and KCl buffers. TEA uptake was not significantly different when the media pH was varied from 6.0 to 8.0. In addition, results of experiments in which intracellular pH was altered with NH4Cl were not consistent with the presence of organic cation/proton exchange. TEA/TEA exchange could not be demonstrated in experiments in which cells were preloaded with 1 mM nonradioactive TEA and uptake of (3H)TEA was measured or in which nonradioactive TEA in the external medium failed to enhance efflux from cells preloaded with (3H)TEA. These results indicate that the basolateral membrane of LLC-PKc10 cells has one or more transport processes for the mediated uptake of organic cations. However, the precise mechanism(s) involved in this transport remains to be elucidated. PMID- 1600124 TI - Hormonal regulation of expression of the angiotensinogen gene in cultured opossum kidney proximal tubular cells. AB - Angiotensinogen (ANG) messenger RNA is expressed in cultured opossum kidney (OK) proximal tubular cells. The aim of these studies was to investigate whether steroid hormones (dexamethasone, estradiol, testosterone, and progesterone) could stimulate the expression of renal ANG gene in vitro. Fusion genes consisting of various lengths of the 5'-flanking region of the rat ANG gene linked to a chloramphenicol acetyl transferase (CAT) reporter gene were constructed and introduced into cultured OK cells. The level of expression of fusion genes was determined by the level of cellular CAT enzymatic activity. The addition of dexamethasone (10(-12) to 10(-6) M) stimulates the expression of the pOCAT (ANG N 1498/+18) fusion gene in OK cells in a dose-dependent manner with a maximum stimulation at 10(-6) M and a half-maximal stimulation at 10(-9) M. Combination of dexamethasone (10(-6) M) and thyroid hormone, L-T3 (10(-6) M), further enhanced the effect of the dexamethasone alone. Testosterone (10(-6) M), estradiol (10(-6) M), and progesterone (10(-6) M) did not have this effect. Moreover, dexamethasone also stimulates the expression of the pOCAT (ANG N 688/+18) but not pOCAT (ANG N-110/+18), pOCAT (ANG N-53/+18) and pOCAT (ANG N 35/+18). These studies demonstrate that the glucocorticoid hormone is effective at stimulating the transcription of the ANG gene in OK cells, but stimulation is not observed from testosterone, estradiol, or progesterone. Moreover, glucocorticoid and L-T3 act synergistically to stimulate the transcription of the ANG gene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600125 TI - Potassium supplementation attenuates experimental hypertensive renal injury. AB - The long-term roles of dietary sodium and potassium on the renal end-organ damage of hypertension were investigated in Wistar-Kyoto (WKY) and in spontaneously hypertensive (SHR) rats. Eight rats from each strain were maintained since 1 month of age on one of four dietary combinations of either low (0.4%) or high (6.0%) NaCl and low (0.51%) or high (7.6%) KCl providing sodium/potassium molar ratios of 1:1, 1:15, 15:1, and 15:15, respectively. Urinary sodium/potassium excretion ratios confirmed the proportion of salts consumed. Systolic blood pressures (SBP) were similar at 5 months of age and at the completion of the study at 9.5 months; SBP was significantly higher in SHR than in WKY rats and was not attenuated by dietary potassium supplementation of a magnitude that raised plasma potassium concentrations. Albumin excretion rate (AER) was also higher in SHR than in WKY rats (P less than 0.0001). In SHR, AER rose further with high sodium intake (P less than 0.035) but, contrary to SBP, was ameliorated by an equimolar addition of potassium (P less than 0.01). Morphologic lesions were generally absent in WKY rats and were more common in SHR as a group (P less than 0.001). In all four SHR groups, the graded histopathologic injury correlated well with measured AER but a major improvement in hypertensive renal lesions occurred largely in the KCl-supplemented, salt-loaded SHR group. These results show a disassociation between the effects of dietary monovalent cations on the level of SBP and their effect on renal injury. Sodium aggravates renal injury and potassium protects against this renal effect of sodium independent of SBP effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600126 TI - Erythropoietin for chronic ambulatory peritoneal dialysis patients: once a week can be enough. PMID- 1600127 TI - Interactions between glomerular mesangial cells, cytokines, and extracellular matrix. AB - This brief overview summarizes recent information on the interactions of glomerular mesangial cells (MC) with soluble cytokines and nonsoluble extracellular matrix (ECM). The presently available knowledge stems largely from glomerular cell culture studies and from experimental work with laboratory animals. ECM production by MC appears to be regulated primarily by the paracrine or autocrine effects of cytokines, such as interleukin 1, platelet-derived growth factor, and transforming growth factor beta. However, ECM itself also affects the behavior of cultured MC, e.g., with regard to cell replication and the production of ECM components and other proteins. At present, little is known about the recognition of ECM and cytokines by MC that allows these interactions to take place. First results indicate that MC, like other cell types, possess surface proteins belonging to the beta 1 integrin family, which serve as specific receptors for ECM molecules. Receptors for the cytokines platelet-derived growth factor, insulin-like growth factor 1, epidermal growth factor, and transforming growth factor beta have also been demonstrated on MC. The expression of various receptors on MC appears to be affected by the ECM substratum. Thus, it is becoming apparent that mesangial ECM is not only important as a mechanical scaffold of the glomerular capillary tuft but that it also contains and conveys information relevant for the regulation of the MC phenotype, e.g., by modulating the MC response to cytokines. The available evidence suggests that alterations of ECM composition in glomerular disease can directly or indirectly affect MC behavior, e.g., by promoting cell replication and further accumulation of ECM, eventually resulting in progressive mesangial and glomerular sclerosis. PMID- 1600128 TI - Reactive oxygen species as glomerular autacoids. AB - There is considerable evidence suggesting that reactive oxygen species (ROS; superoxide anion, hydrogen peroxide, hydroxyl radical, hypochlorous acid) are implicated in the pathogenesis of toxic, ischemic, and immunologically mediated glomerular injury. The capacity of glomerular cells, especially mesangial cells, to generate ROS in response to several stimuli suggests that these autacoids may play a role in models of glomerular injury that are independent of infiltrating polymorphonuclear leukocytes and monocytes. The mechanisms whereby ROS formation results in morphologic lesions and in modifications of glomerular permeability, blood flow, and filtration rate have been inferred from in vitro studies. They involve direct and indirect injury to resident cells (mesangiolysis) and glomerular basement membrane (in concert with metalloproteases) and alteration of both the release and binding of vasoactive substances, such as bioactive lipids (e.g., prostaglandin E2, prostacyclin, thromboxane), cytokines (e.g., tumor necrosis factor alpha), and possibly endothelium-derived relaxing factor. The importance of such processes appears to be modulated by the intrinsic antioxidant defenses of the glomeruli. Further studies are needed to address the role of ROS in human glomerular diseases. PMID- 1600129 TI - Immune damage to the mesangium: antibody- and complement-mediated stimulation and destruction of mesangial cells. AB - The deposition of immune complexes in the tissue results in complement activation leading to the formation of the lytic C5b-9 complex. Tissue cells are relatively resistant to complement attack due to cellular mechanisms such as removing C5b-9 from the surface and the expression of membrane proteins, which regulate complement activation and attack on the cell surface. Hence, cell killing is not an important consequence of complement activation on nucleated cells. On the other hand, the sublethal C5b-9-membrane interaction leads to various cellular responses, among them the synthesis of eicosanoids, cytokines, matrix-degrading proteases, and extracellular matrix, resulting in the modification of cell proliferation, leukocyte function, matrix degradation, and the formation of scar tissue. Thus, the complement-dependent immune damage is caused by secondary mediators, either derived from leukocytes or mesangial cells, rather than by a direct C5b-9-mediated killing. PMID- 1600130 TI - Morphologic and functional consequences of immune-mediated mesangiolysis: development of chronic glomerular sclerosis. AB - The i.v. injection of a rabbit anti-rat thymocyte serum (ATS) induces mesangiolysis in rats, followed by a mesangioproliferative glomerulonephritis (4 to 7 days after antibody). This proliferative lesion disappears 4 to 6 wks after antibody. In order to induce an antibody-mediated sclerotic glomerular disease, uninephrectomized rats received ATS twice at 6-wk interval. At 6 months after the first antibody injection, albuminuria, arterial blood pressure, and inulin clearances were evaluated and renal morphologic studies were performed. At the time of evaluation, mean arterial blood pressure and inulin clearances were not different between animals that received the antibody and uninephrectomized controls. Rats that were injected with antibody, however, had significantly higher albuminuria compared with that of controls. Glomeruli of rats with ATS revealed expansion of the glomerular mesangial matrix and focal sclerosis. A semiquantitative morphologic analysis revealed an increased incidence of glomerular lesions and a higher glomerular damage index in kidneys of nephritic rats. These data demonstrate that the repetitive injection of ATS to unilaterally nephrectomized rats induces a model of chronic glomerular sclerosis. PMID- 1600131 TI - Macromolecular properties that promote mesangial binding and mesangiopathic nephritis. AB - The hydrodynamic size, electrostatic charge, and specificity are established determinants of the site of glomerular localization of macromolecules. Larger macromolecules or aggregates and anionic charge are associated with mesangial deposits, despite the fact that the mesangial matrix bears a negative charge similar to that of the capillary wall. Antigens such as Sendai virus, a model infectious pathogen, gliadin, a model dietary/environmental agent and fibronectin, a model endogenous macromolecule, bind to mesangial cells in vitro on the basis of cell surface glycoconjugates. Nonantibody immunoglobulin A, which does not bind to cells directly, binds to these elements via different carbohydrate specificities (simple sugar inhibition). Such binding promotes or augments macromolecular deposition in the mesangium. More significantly, mesangial deposits per se are not pathogenic, because normal renal function can be observed with florid deposits. Pathogenic deposits must have properties that alter mesangial cell metabolism or interaction with the matrix. Although complement activation is well recognized, complement-independent mechanisms related to cell surface modulation are being recognized. In vitro, antigen/immunoglobulin A aggregates alter mesangial cell eicosanoid synthesis. In vivo, large-lattice cross-linking by particulate antigen promotes hematuria. We conclude that the binding of macromolecules to cells and the cross-linking of cell surface molecules cause alterations in the mesangial cells and therefore in glomerular function. The mesangial cell, rather than a passive respondent, is an active participant in the genesis of glomerulonephritis. PMID- 1600132 TI - Immunopathological aspects of immunoglobulin A nephropathy and other mesangial proliferative glomerulonephritides. AB - Immunoglobulin A nephropathy (IgAN) is an immune complex (IC) glomerulonephritis (GN) that represents one of the most common forms of primary glomerular disease. Proliferation of mesangial cells and the increase of mesangial matrix are histological hallmarks of mesangioproliferative GN. Increased serum levels of IgA, polymeric IgA, IgA rheumatoid factor, IgA-IC, and spontaneous or pokeweed mitogen-induced production of IgA by peripheral blood mononuclear cells are major humoral immune alterations reported in IgAN. Recently, we focused on the role of cytokines and growth factors in the mediation of glomerular injury. Platelet derived growth factor, transforming growth factor beta, interleukin (IL)-1 and IL 6 are expressed by and act on mesangial cells. Increased expression of platelet derived growth factor was found in both an active model of IgAN and in renal biopsies of patients with proliferative GN. A strict correlation between increased expression of B-chain mRNA and mesangial proliferation was found. Cytokines such as IL-1, interferon gamma, and IL-6, released by infiltrating mononuclear cells or produced locally by mesangial cells, affect the glomerular response to IgA-IC. In a passive murine experimental model of IgAN, IL-1 and interferon gamma increased mesangial hypercellularity, whereas IL-6 was highly pathogenic when associated to IL-1. In conclusion, classical immunological mechanisms in mesangial GN could interact with other pathways involving cytokines and growth factors in the progression of glomerular injury. PMID- 1600133 TI - Dietary antigens and primary immunoglobulin A nephropathy. AB - To investigate the role of dietary components in immunoglobulin A mesangial nephropathy (IgAGN), this study focused on gliadin, based on the reported association between coeliac disease and IgAGN as well as the pilot observation that a gluten-free diet was able to reduce the levels of circulating IgA immune complexes (IgAIC). IgA mesangial deposits in mice were induced by oral immunization with gliadin and in rats by inducing alcoholic liver cirrhosis, which increased the levels of IgA against dietary antigens (Ag). Gliadin was able to bind to cultured mesangial cells by a lectinic bond, which was reversed by competitive sugars. Binding increased mesangial cell tumor necrosis factor synthesis and decreased prostaglandin E2 production. Several gluten lectinic fractions modulate leukocyte oxidative metabolism, cytotoxicity, and chemotaxis. In IgAGN patients, serum IgA to dietary Ag were sporadically positive and IgAIC containing IgA to dietary components were significantly increased. The affinity of serum IgA to various lectins was increased in some patients. Conversely, no substantial deposition in renal tissue of dietary Ags was observed by immunofluorescence. A gluten-free diet, given to IgAGN patients with high levels of circulating IgAIC and positive antigliadin IgA, was followed by a decrease in the mean levels of both IgAIC and IgA to various dietary Ag, parallel to a reduction in proteinuria. These data suggest that dietary components, such as Ag or lectins, may play a role in IgAGN by promoting IgAIC formation and perhaps favoring mesangial localization via lectinic interactions. PMID- 1600134 TI - Renal structure and function in insulin-dependent diabetes mellitus and type I membranoproliferative glomerulonephritis in humans. AB - Renal pathological changes of diabetes include thickening of all renal extracellular basement membranes and the mesangial matrix and, to a lesser extent, mesangial cell expansion. Two renal lesions appear critical in diabetic nephropathy. Mesangial expansion out of proportion to the size of the glomerulus is related to proteinuria, hypertension, and declining GFR. Arteriolar hyalinosis is related to global glomerulosclerosis, and both are correlated with the clinical features of nephropathy. By the time renal dysfunction is clinically detectable, these lesions tend to be advanced. Interstitial volume may be increased in insulin-dependent diabetes mellitus, particularly in areas containing sclerotic glomeruli or marked tubular atrophy. Parallel findings were documented for type I membranoproliferative glomerulonephritis in which the increased mesangial volume fraction was related to decreased GFR, increased glomerular permeability to protein, and hypertension. As in diabetes, the cortical interstitial volume fraction is correlated with functional abnormalities in type I membranoproliferative glomerulonephritis. Thus, in both of these chronic glomerular disorders, mesangial expansion and interstitial expansion are associated with disordered renal function. Thus, it is not true that glomerular structural changes correlate poorly with glomerular function. Whether it is the glomerular or interstitial pathology or both that is causally responsible for the dysfunction requires further study. PMID- 1600135 TI - Growth factors and the mesangium. AB - Growth factors are prime candidates to mediate and modulate the functions of the mesangium. Mesangial cells are effector cells producing a number of growth factors that act in an autocrine manner to regulate their own function. Mesangial cells are also targets for growth factors released from neighboring glomerular cells or infiltrating cells and platelets. Growth factors may promote hypertrophy, proliferation, matrix metabolism, and immune-inflammatory and vasoactive properties of mesangial cells. These peptides represent important mediators of mesangial cell responses to injury. Platelet-derived growth factor mediates predominantly cell proliferation, whereas transforming growth factor beta mediates mesangial cell matrix expansion. Mesangial cells may also modulate some of the hemodynamic effects of growth factors, such as the increased renal vascular resistance in response to platelet-derived growth factor and epidermal growth factor or the increased RBF and GFR in response to insulin-like growth factor-1. Changes in the expression of growth factors of their receptors during the course of glomerular injury point to a potential role in mediating some of the pathologic changes in vivo. Several agents appear to antagonize the mitogenic and perhaps other effects of growth factors in mesangial cells. Such agents include adenylate cyclase as well as guanylate cyclase agonists. Recent studies also suggest that some traditional vasoactive agents may activate metabolic processes in mesangial cells similar to peptide growth factors. Collectively, these studies point to the interaction of both hemodynamic and metabolic factors in the response and contribution of glomerular and specifically mesangial cells to injury. PMID- 1600136 TI - The activated mesangial cell: a glomerular "myofibroblast"? AB - The glomerular mesangial cell may have several important beneficial functions in the normal glomerulus. These include the production of growth factors to allow normal cell turnover, the provision of structural support for the capillaries via the production of mesangial matrix, and the modulation of glomerular hemodynamics via their contractile properties. However, in various types of glomerular injury, the mesangial cell may acquire characteristics of a "myofibroblast", which may in fact be injurious to the glomerulus. These "activated" mesangial cells can be shown to be proliferating by one or more mechanisms that are mediated by platelets and that also involve the local production of platelet-derived growth factor. Like myofibroblasts in other tissues, the mesangial cell acquires smooth muscle cell-like properties, characterized by the de novo expression of alpha smooth muscle actin, and by the development of fibroblast-like properties, characterized by the production of interstitial collagens in addition to normal mesangial matrix constituents. Identifying therapeutic strategies that prevent this phenotypic modulation of the mesangial cell may provide new ways to treat golmerular diseases. PMID- 1600137 TI - The role of interstitial cells in the progression of renal diseases. AB - Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600138 TI - Renal growth responses to acute and chronic injury: routes to therapeutic intervention. AB - Knowledge of the control of cell growth and extracellular matrix deposition has assumed center stage in the understanding of how the diseased kidney responds to injury. After acute tubular injury, there may be reversible, partial depolarization of renal cells or cell necrosis. The latter requires a regenerative response, which could be under the control of growth factors such as epidermal growth factor (EGF). Up-regulation of EGF receptors on viable cells provides the cell with an enhanced growth response despite a reduction in EGF production by the kidney. Acute glomerular injury involves a highly complex network of cytokines and growth inhibitors, the most important of which appear to be platelet-derived growth factor as a mitogen and transforming growth factor beta as an activator of extracellular matrix deposition. The long-term growth responses of the kidney to injury, reflected by chronic renal diseases, include tubular hypertrophy in those nephrons which are less affected by the primary disease. Tubular cell enlargement appears to proceed along a pathway that is different from the growth in cell size which precedes cell division, at least as indicated by a fundamentally different pattern of early gene expression. This pattern is not suggestive of a classical growth factor-initiated process. Other chronic changes that seem to correlate well with the progression of human disease are tubular atrophy and interstitial fibrosis. Growth factors produced by tubular cells may cause proliferation and matrix deposition by adjacent interstitial fibroblasts. A scheme is proposed in which low-grade ischemic injury to tubular cells, secondary to microvascular injury, leads to tubular atrophy, the release of growth factors, interstitial fibrosis, and the obliteration of peritubular capillaries. This would aggravate primary glomerular injury by compromising the vascular outflow from the glomerulus and would account for the long-recognized association between tubulo-interstitial injury and the progression of a variety of renal diseases. The use of growth factors to stimulate specific growth responses, antibodies, or inhibitory molecules to inhibit scarring generated by cytokines and the potential for genetic manipulation of the kidney provide future avenues for manipulating the growth response of the diseased kidney. PMID- 1600139 TI - An approach to the structure and function of the glomerular mesangium. AB - The mesangium of the glomerulus is a connective tissue tree arising at the vascular pole of the glomerulus and supporting the glomerular capillaries. It is partly covered by a basement membrane that follows the epithelial cells from the peripheral glomerular capillary wall over the supporting tissue. The capillary endothelium does not normally have a separate basement membrane. The endothelium has fenestrations that open directly into the mesangium and allow blood plasma and tracers to flow into the mesangium. The fenestrations partially restrict (or sieve) particles over 405 A in mean length from entry. Tracers move in intercellular channels and are filtered and concentrated by the basement membrane at the sides of the mesangium or by mesangial matrix filaments in the channels between cells. The irregular distributions of flow, matrix, and concentrations of tracers may account for irregular lobular reactions in glomerular disease. Two main pathways of flow seem to be (1) through the basement membrane and between the epithelial foot processes to form part of the glomerular filtrate and (2) into the efferent capillaries through their mesangial fenestrations. Intrinsic mesangial cells can now be regarded as myofibroblasts associated with the production of the connective tissue matrix. These cells hold the basement membrane to maintain the shape of the glomerular capillaries, they swell readily, and they can constrict like smooth muscle cells with appropriate stimulation. These reactions may enable them to control the flow of blood through the capillary network in glomerular disease. Mesangial cells can take up large amounts of foreign material within 24 h. Intrinsic mesangial cells and monocytes can increase in numbers in disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600140 TI - The mesangial phagocyte and its regulation of contractile cell biology. AB - The mesangium constitutes the core of the renal glomerulus. It consists of the matrix, composed of mucopolysaccharides and glycoproteins, and two cell types. The predominant cell type is the mesangial cell, resembling a vascular smooth muscle cell. Up to 15% of the mesangial cell population additionally consists of resident mesangial phagocytes. These are derived from the bone marrow and belong to the family of mononuclear leukocytes. They are phagocytic, express Fc and C3 receptors, and display membrane Ia antigens. They syngeneically stimulate lymphocyte proliferation via antigen presentation. They are equally potent allogeneic stimulating cells in mixed lymphocyte culture. The mesangium is also the preferred locus of the induced migration of monocytes in inflammatory and proteinuric states. The presence of both normally resident and inflammation associated mesangial phagocyte is lipid dependent. Hyperlipidemia increases the population of mesangial phagocytes. Lipid restriction decreases their number and, as a result, diminishes the allogenicity of renal transplants and blunts the progression of glomerulonephritis. One signal regulating the infiltration of the mesangium by mononuclear phagocytes appears to be a complex neutral lipid that is highly and specifically chemotactic for monocytes. It is released by the contractile mesangial cell in response to the stimulation of its Fc receptor and to the mesangial deposition of macromolecules. Both resident and inflammatory mesangial phagocytes secrete factors that remodel the mesangial matrix, stimulate mesangial cell proliferation, alter glomerular basement membrane permeability, and regulate blood flow. The persistence of mononuclear phagocytes in an activated state within the mesangium contributes to the marked alteration in mesangial structure that eventuates in glomerulosclerosis in both immune and nonimmune models of glomerular injury. PMID- 1600141 TI - Mesangial cell proteoglycans: synthesis and metabolism. AB - In cultures of human adult glomerular mesangial cells, large chondroitin sulfate proteoglycans (CSPG) and small dermatan sulfate proteoglycans (DSPG) are synthesized. The large CSPG has a core protein, M(r) of 400,000 (major) and M(r) of 500,000 (minor), and binds to hyaluronic acid to form large aggregates. The two small DSPGs (Mr of approximately 350,000 and M(r) of approximately 200,000) were related to biglycan and decorin, respectively. The majority of these proteoglycans were located in the culture medium, but a hydrophobic form of the CSPG was extracted from the cell layer. Mesangial cells in the growing phase synthesized and secreted all three types of proteoglycans, but in cells arrested in G0 by serum deprivation the incorporation of (35S)sulfate in CSPG was drastically reduced. In the same cells stimulated to proliferate by replacing the medium with one containing serum, the synthesis of CSPG dramatically enhanced. The synthesis of CSPG and DSPG was also elevated in cells cocultured with cytokines but in contrast was significantly reduced when cultured in medium containing hyperglycemic levels of glucose. Finally, preliminary experiments are reported that indicate that CSPG and DSPG bind to low-density lipoproteins in vitro. These observations suggest a possible specialized function for proteoglycans in cellular processes characteristic of glomerular disease. PMID- 1600142 TI - Evolution of the plastid ribosomal RNA operon in a nongreen parasitic plant: accelerated sequence evolution, altered promoter structure, and tRNA pseudogenes. AB - The nucleotide sequence of a 7.4 kb region containing the entire plastid ribosomal RNA operon of the nongreen parasitic plant Epifagus virginiana has been determined. Analysis of the sequence indicates that all four rRNA genes are intact and almost certainly functional. In contrast, the split genes for tRNA(Ile) and tRNA(Ala) present in the 16S-23S rRNA spacer region have become pseudogenes, and deletion upstream of the 16S rRNA gene has removed a tRNA(Val) gene and most of the promoter region for the rRNA operon. The rate of nucleotide substitution in 16S and 23S rRNAs is several times higher in Epifagus than in tobacco, a related photosynthetic plant. Possible reasons for this, including relaxed translational constraints, are discussed. PMID- 1600143 TI - Ribosomal RNA genes of Phaseolus coccineus. I. AB - rDNA fragments, including the whole intergenic spacer (IGS) region of P. coccineus, were cloned into dephosphorylated pUC 13 plasmid. Four clones of different insert size were analysed. Restriction patterns and physical maps of these length variants (pPH1, pPH2, pPH5, pPH6) were performed through complete Eco RI cleavage and partial digestion with Hpa II, Hae III, Sau 3AI, Sma I. Evidence was obtained that the length heterogeneity of the four genes was mainly due to a differing number of about 170 bp sub-repeating elements in the IGS. Indeed, there are 16 of these in pPH1, about 34 in pPH2, 10 in pPH5 and about 60 in pPH6. The sequence analysis of pPH6 sub-repeats revealed that there are two types of sub-repeats: short ones (S) of 162 bp and long ones (L) of 176 bp. The homology between S and L is high (93.8%). S and L elements are present in at least three of the four genes investigated, as shown by a restriction pattern obtained with Hae III digestion to completion. The relative frequency of S and L types, however, differs among the four genes. The possible functional meaning of the sub-repeat structure is discussed on the basis of the homology between the S and L sequences on the one hand and on the other the ribosomal sequences of: i) Xenopus promoter(s); ii) wheat block A sub-repeats; iii) presumptive promoter(s) of wheat. PMID- 1600144 TI - The activation process of Arabidopsis thaliana A1 gene encoding the translation elongation factor EF-1 alpha is conserved among angiosperms. AB - In Arabidopsis thaliana, the activation process of the A1 EF-1 alpha gene depends on several elements. Using the GUS reporter gene, transient expression experiments have shown that mutations of upstream cis-acting elements of the A1 promoter, or the deletion of an intron located within the 5' non-coding region, similarly affect expression in dicot or monocot protoplasts. The results reported here strongly suggest that this 5' intron is properly spliced in Zea mays. We show that two trans-acting factors, specifically interacting with an upstream activating sequence (the TEF 1 box), are present in nuclear extracts prepared from A. thaliana, Brassica rapa, Nicotiana tabacum and Z. mays. In addition, a DNA sequence homologous to the TEF 1 box, found at approximately the same location within a Lycopersicon esculentum EF-1 alpha promoter, interacts with the same trans-acting factors. Homologies found between the A. thaliana and L. esculentum TEF 1 box sequences have allowed us to define mutations of this upstream element which affect the interaction with the corresponding trans-acting factors. These results support the notion that the activation processes of A. thaliana EF-1 alpha genes have been conserved among angiosperms and provide interesting data on the functional structure of the TEF 1 box. PMID- 1600145 TI - Characterization of cymbidium mosaic virus coat protein gene and its expression in transgenic tobacco plants. AB - Cymbidium mosaic virus (CyMV) is the most prevalent virus infecting orchids. Here, we report the isolation of partial cDNA clones encoding the genomic RNA of CyMV. Like most of the polyadenylated monopartite positive-strand RNA viruses, the open reading frame (ORF) coding for the viral coat protein (CP) is located at the 3' end. The ORF predicts a polypeptide chain of 220 amino acids with a molecular weight of 23,600. Sequence comparison of this ORF to the CP sequences of potato virus X(PVX) and white clover mosaic virus (WClMV) revealed a strong amino acid homology in the mid-portion of the CP, but the overall homology was low. The CyMV CP gene was placed downstream of a cauliflower mosaic virus 35S promoter and the chimaeric gene was transferred into Nicotiana benthamiana. Transgenic plants expressing the CyMV CP were protected against CyMV infection. PMID- 1600146 TI - Characterization of a pollen-specific cDNA clone from Nicotiana tabacum expressed during microgametogenesis and germination. AB - This report describes the isolation and characterization of a cDNA clone representing a gene specifically expressed in pollen. A cDNA library was constructed against mRNA from mature pollen of Nicotiana tabacum. It was screened differentially against cDNA from mRNA of leaf and of pollen. One clone, NTPc303, was further characterized. On northern blot this clone hybridizes to a transcript 2100 nucleotides in length. NTPc303 is abundant in pollen. Expression of the corresponding gene is restricted to pollen, because no other generative or vegetative tissue contains transcripts hybridizing to NTPc303. Expression of NTP303 is evolutionarily conserved: homologous transcripts are present in pollen from various plant species. The first NTP303 transcripts are detectable on northern blot at the early bi-nucleate stage and accumulate until the pollen has reached maturity. During germination and pollen tube growth in vitro new NTP303 transcripts appear. This transcription has been proved by northern blots as well as by pulse labelling experiments. Nucleotide sequence analysis revealed that NTPc303 has an open reading frame coding for a predicted protein of 62 kDa. This protein shares homology to ascorbate oxidase and other members of the blue copper oxidase family. A possible function for this clone during pollen germination is discussed. PMID- 1600147 TI - Auxin rapidly down-regulates transcription of the tryptophan decarboxylase gene from Catharanthus roseus. AB - The enzyme tryptophan decarboxylase (TDC) (EC 4.1.1.28) converts tryptophan into tryptamine, and thereby channels primary metabolites into indole alkaloid biosynthesis. The production of these secondary metabolites in suspension cells of Catharanthus roseus depends on medium composition. Of the possible variables, we investigated the effect of hormones on the expression of the tdc gene in cell cultures. Omission of NAA from the growth medium resulted in accumulation of tdc mRNA. The addition of 1-naphthaleneacetic acid (NAA), indoleacetic acid (IAA) or 2,4-dichlorophenoxyacetic acid (2,4-D) rapidly reduced the enhanced tdc transcript level. Cytokinin was unable to suppress the enhanced transcript level. Hairy roots transformed by Agrobacterium rhizogenes also showed a reduction of the tdc mRNA level after NAA addition. Run-off transcription experiments showed that the down-regulation takes place at the transcriptional level within 15 minutes and independent of de novo protein synthesis. Thus one of the mechanisms which control the activity of terpenoid indole alkaloid biosynthesis in C. roseus cell cultures is the negative regulation by auxin of the gene involved in the first committed step. PMID- 1600148 TI - Coordinated regulation of two indole alkaloid biosynthetic genes from Catharanthus roseus by auxin and elicitors. AB - Catharanthus roseus (periwinkle) produces a wide range of terpenoid indole alkaloids, including several pharmaceutically important compounds, from the intermediate strictosidine. The complete mRNA sequence for the enzyme strictosidine synthase (SSS) was determined. Comparison of the primary structure of the encoded protein with the amino-terminal sequence of purified SSS indicated the presence of a signal peptide of 31 amino acids in the putative primary translation product. SSS is encoded by a single-copy gene indicating that isoenzymes reported by others are formed post-translationally from a single precursor. The sss gene and the tryptophan decarboxylase gene (tdc), encoding another enzyme essential for indole alkaloid biosynthesis, are coordinately regulated. In plants steady-state mRNA levels are highest in roots. In cell suspension cultures the genes are rapidly down-regulated by auxin. In contrast, both genes are strongly induced by fungal elicitors such as Pythium aphanidermatum culture filtrate or yeast extract. Induction is a rapid, transcriptional event occurring independent of de novo protein synthesis. These results show that a first important regulatory step in the complex process leading to indole alkaloid accumulation in C. roseus suspension cells is transcription of the biosynthetic genes. PMID- 1600149 TI - Direct screening for high-level expression of an introduced alpha-amylase gene in plants. AB - A method is described for obtaining transgenic plants with a high level of expression of the introduced gene. Tobacco protoplasts were transformed with an expression construct containing a translational fusion between mature alpha amylase from Bacillus licheniformis and the signal peptide of the tobacco PR-S protein. A total number of 5200 transformed protoplasts was cultured to microcalli and screened for alpha-amylase expression by incubation on media containing starch followed by staining with iodine. The calli were divided into four classes, based on the resulting halo sizes on the plates. The halo sizes were found to correlate with the expression levels in transgenic plants regenerated from the calli. The expression levels varied between 0 and 0.5% of soluble leaf protein in the regenerated transgenic plants. Wider implications of this method are discussed. PMID- 1600150 TI - The isolation and functional characterisation of a B. napus acyl carrier protein 5' flanking region involved in the regulation of seed storage lipid synthesis. AB - Acyl carrier protein (ACP) is a key component of the fatty acid biosynthetic machinery in plants. A 1.4 kb 5' flanking region of a Brassica napus ACP gene (ACP05) was transcriptionally fused to the reporter gene beta-glucuronidase (GUS), and expression of the chimeric gene monitored in transgenic tobacco. GUS activity was found to increase through seed development reaching a maximum value, coincident with the most active phase of storage lipid synthesis that was, on average, 100-fold higher than that observed in leaf. In control plants transformed with CaMV 35S-GUS constructs, GUS activity was similar in leaf and all stages of seed development. Based on average values, the level of GUS expression obtained via the ACP promoter was comparable to that obtained from the CaMV 35S promoter. We therefore conclude that the isolated 5' ACP flanking sequence represents a strong promoter element involved in the developmental regulation of storage lipid synthesis in B. napus seed tissue. Putative regulatory elements in the 5' upstream region of ACP05 were identified by dot matrix analysis and by sequence comparison with the upstream regions from a second seed-expressed rape ACP gene and from an Arabidopsis ACP gene. PMID- 1600151 TI - Comparison of the structure and nucleotide sequences of vicilin genes of cocoa and cotton raise questions about vicilin evolution. PMID- 1600152 TI - Nucleotide sequence of an Arabidopsis thaliana oleosin gene. PMID- 1600154 TI - Sequence of two acetohydroxyacid synthase genes from Zea mays. PMID- 1600153 TI - Chemical detection of Z-DNA within the maize Adh1 promoter. AB - Z-DNA is a left-handed helix which can form within tracts of alternating purines and pyrimidines. Tracts of potential Z-DNA identified by sequence inspection are often noted within regulatory portions of genes, but evidence that these tracts of sequence actually exist as Z-DNA is very limited, and not available for any plant gene. In this study, the chemical probes osmium tetroxide, diethylpyrocarbonate and hydroxylamine were used to show that a tract of alternating purines and pyrimidines in the Adh1 promoter (from -311 to -325) actually assumes a Z-DNA conformation under superhelical stress in vitro. PMID- 1600155 TI - Sequence analysis of an alfalfa 25S rRNA. PMID- 1600156 TI - Nucleotide sequence of cDNA encoding alpha-luffin, a ribosome-inactivating protein from Luffa cylindrica. PMID- 1600157 TI - cDNA cloning and sequencing of the bean yellow mosaic virus nuclear inclusion protein genes. PMID- 1600158 TI - Nucleotide sequence of a nuclear tRNA(Tyr) gene from Triticum aestivum. PMID- 1600159 TI - Sequence of the Phytophthora infestans glyceraldehyde-3-phosphate dehydrogenase encoding gene (gpdA). PMID- 1600160 TI - Fluidity of the 350 bp tandemly repeated DNA family of Brassica nigra. PMID- 1600161 TI - Sequence analysis of 18S ribosomal RNA gene in Fragaria x Ananassa Duch. cultivated octoploid strawberry. PMID- 1600162 TI - Transcriptional and post-transcriptional regulation of gene expression in plants. PMID- 1600163 TI - The molecular biology of disease resistance. PMID- 1600164 TI - The search for the proteinase inhibitor-inducing factor, PIIF. PMID- 1600165 TI - Molecular basis of disease susceptibility in the Texas cytoplasm of maize. PMID- 1600166 TI - The chloroplast genome. PMID- 1600168 TI - The biochemistry and molecular biology of plant lipid biosynthesis. PMID- 1600169 TI - Plant and organ development. PMID- 1600167 TI - Agrobacterium and plant genetic engineering. PMID- 1600172 TI - Ethical decision making by nurses in HIV/AIDS situations. AB - The purpose of this study was to assess the ethical decision making levels of nurses in HIV/AIDS situations. Using an adapted form of Crisham's Nursing Dilemma Test, RNs in various settings in Ohio ranked their reasons for action in responding to vignettes. Findings suggest that nurses are basing their clinical decisions in HIV/AIDS situations on practical considerations rather than on nursing principles. Education programs based on the findings from this study will enhance the use of nursing principles. PMID- 1600171 TI - Developmental aspects of the Rhizobium-legume symbiosis. PMID- 1600173 TI - Engineering controls. PMID- 1600170 TI - Molecular biology of fruit ripening and its manipulation with antisense genes. AB - Considerable progress in tomato molecular biology has been made over the past five years. At least 19 different mRNAs which increase in amount during tomato fruit ripening have been cloned and genes for enzymes involved in cell wall degradation (polygalacturonase and pectinesterase) and ethylene synthesis (ACC synthase) have been identified by conventional procedures. Transgenic plants have been used to identify regions of DNA flanking fruit-specific, ripening-related and ethylene-regulated genes and trans-acting factors which bind to these promoters have also been identified. Antisense genes expressed in transgenic plants have proved to be highly effective for inhibiting the specific expression of ripening-related genes. These experiments have changed our understanding of how softening occurs in tomato fruit. Antisense techniques have also been used to identify genes encoding enzymes for carotenoid biosynthesis (phytoene synthase) and ethylene biosynthesis (the ethylene-forming enzyme). The altered characteristics of fruit transformed with specific antisense genes, such as retarded ripening and resistance to splitting, may prove to be of value to fruit growers, processors and ultimately the consumer. PMID- 1600174 TI - Impact of case management on hospital charges of PWAs in Georgia. AB - To determine the effects of case management in controlling hospital based costs for persons with AIDS (PWAs), a retrospective review of records of deceased PWAs was performed. The study compared diagnosis-to-death hospital charges for PWAs who received care under a care management model (n = 60) with PWAs receiving care within a non-case managed approach (n = 60). Hospital charges were adjusted for inflation. PWAs receiving care within the case managed model had significantly lower hospital-based changes than the non-case managed group. Additionally, PWAs in the case managed group lived significantly longer between HIV diagnosis and death, and lived longer between their first AIDS-related hospital admission and death. PMID- 1600175 TI - Human immunodeficiency virus and immigration status in the United States. AB - The number of HIV-infected immigrants is increasing in cities across the United States. A case study explores the complexities of the immigration process as it relates to HIV infection; implications for nursing practice are discussed. By understanding the immigration process, nurses are able to identify and refer illegal residents who are HIV infected to appropriate social-service agencies, thereby providing more comprehensive care to patients and their families. PMID- 1600176 TI - Who is better prepared to fill the role of case manager? Nurses or social workers? Counterpoint. PMID- 1600177 TI - Who is better prepared to fill the role of case manager? Nurses or social workers? Point. PMID- 1600178 TI - Nursing students and occupational exposure to HIV. PMID- 1600179 TI - Nursing faculty's knowledge and attitudes toward persons with AIDS. AB - The research examined knowledge, fear, homophobia, and the willingness to care for persons with AIDS. The subjects were 45 faculty members from nursing programs in a mid-southern state. The study was an extension of an earlier study by Lester and Beard (1988). A 56-item questionnaire consisting of knowledge and attitude questions was used. Attitude questions were categorized into fear, homophobia, and the intent to give care. With the level of significance set at (p less than .01), homophobia and fear were significantly correlated positively. Knowledge was not significantly correlated with any of the variables. Findings suggest that AIDS education should be directed toward changing attitudes and values by promoting learning in the affective domain. PMID- 1600180 TI - A glimpse of community-based rehabilitation in China. AB - As in other developing countries, community-based rehabilitation (CBR) in China is very important. However, because of differences in the social system, economy, and cultural level, it is impossible to implement a uniform model of CBR. This paper introduces material to show how CBR in China tends to be spontaneous. Experience of CBR stations in Shenyang has initiated a new approach to CBR within the cultural characteristics of China. PMID- 1600182 TI - Use of the myometer in assessing stroke patients--a cautionary tale. PMID- 1600181 TI - Minimal trauma causing fractures in patients with spinal cord injury. AB - The osteoporosis that accompanies spinal cord injury renders bones more susceptible to fracture following minor degrees of trauma. Diagnosis is often delayed due to a subtle presentation with non-specific signs. Three cases are reported that illustrate characteristic features of long-bone fractures in spinal cord injury. PMID- 1600183 TI - Twelve-year clinical course of schizophrenia from 1971/73 to 1983. A longitudinal study of clinical course and a cross-sectional study 12 years after hospital or night-clinic treatment. AB - Two samples of 46 schizophrenic patients, one of new attendees at a night clinic in 1971-73 and the other of hospitalized patients matched for age and sex, were followed up 12 years later. Seven of the former and two of the latter had died, all from self-destructive acts. Of the survivors, one-third were rated inconspicuous with regard to psychopathology, one-fifth as conspicuous only to a psychiatrist, and only one-quarter as very conspicuous, even to a layperson. During the first 4 years the night clinic patients showed signs of an insidious chronic course; substantially fewer (17.6% compared with 28.6%) were hospitalized at the time of follow-up, though far more were receiving outpatient or semi inpatient care. In both samples self-isolation and inadequate rehabilitation for work were marked; 72% and 62% respectively were dependent on a disability pension, and only 15% and 20% were employed at work in keeping with their training and experience. Just under half lived alone, and 30-40% had no contact with friends/acquaintances. Longitudinal analysis disclosed a marked decrease in the number and duration of overt phases and stays in hospital, progressive aggravation or residual symptoms in quiescent intervals, and similar decline in ability to work and earn a living. Covariance analysis revealed a significantly greater reduction in total hospitalization in night clinic patients. PMID- 1600184 TI - Validity and discriminant ability of the HAQ Functional Index in early rheumatoid arthritis. AB - A sensitive and valid instrument is needed in the earliest stages of rheumatoid arthritis (RA) for the measurement of functional disability. A French version of the Health Assessment Questionnaire Functional Disability Index (HAQ) has been developed, validated in an early RA sample (i.e. with disease duration less than 5 yr; n = 50), and compared with longstanding RA (n = 32) and control subjects (n = 59). Five factors provided by principal components analysis accounted for 75% of the variability of the HAQ score (construct validity). It appeared to be significantly correlated with clinical and radiological variables and to be reproducible (r intraclass = 0.964). It proved to be discriminant in groups with various levels of disability (HAQ score = 1.332 in early RA, 1.745 in longstanding RA, and 0.152 in controls; p less than 10(-5). Finally, the validity of the original scoring method of the HAQ, as compared with other scoring methods, was confirmed. PMID- 1600185 TI - An evaluation of the hemiplegic patient based on the Bobath approach: a reliability study. AB - The intra- and inter-rater reliability of a motor function evaluation of stroke patients, based on the Bobath approach, was studied. The intraclass correlation coefficient (ICC) was used to determine the degree of agreement between repeated measurements on the same patient taken by the same rater and between measurements taken by three raters on the same patient. In the intra-rater study, each of 19 patients was evaluated in three different sessions by one of 19 raters. In the inter-rater study 18 patients were each evaluated by three different raters. The intra-rater data were highly reliable, with ICCs of 0.95 and 0.97 for the upper and lower limbs respectively. For the inter-rater study, the ICCs were 0.79 and 0.77 for the upper and lower limbs respectively. It can therefore be concluded that this instrument, previously demonstrated to quantify patient progress, is also reliable both in intra- and inter-rater dimensions. PMID- 1600186 TI - Principal components analysis of an evaluation of the hemiplegic subject based on the Bobath approach. AB - An evaluation based on the Bobath approach to treatment has previously been developed and partially validated. The purpose of the present study was to verify the content validity of this evaluation with the use of a statistical approach known as principal components analysis. Thirty-eight hemiplegic subjects participated in the study. Analysis of the scores on each of six parameters (sensorium, active movements, muscle tone, reflex activity, postural reactions, and pain) was evaluated on three occasions across a 2-month period. Each time this produced three factors that contained 70% of the variation in the data set. The first component mainly reflected variations in mobility, the second mainly variations in muscle tone, and the third mainly variations in sensorium and pain. The results of such exploratory analysis highlight the fact that some of the parameters are not only important but also interrelated. These results seem to partially support the conceptual framework substantiating the Bobath approach to treatment. PMID- 1600187 TI - Extent of pyramidal tract wallerian degeneration in the brain stem on MRI and degree of motor impairment after supratentorial stroke. AB - The relationship between Wallerian degeneration in the brain stem and degree of motor impairment is discussed. Using MRI we studied 172 supratentorial stroke patients, whose motor impairment was graded according to Brunnstrom stage. Wallerian degeneration was represented by a T2 high-intensity area in the brain stem, and its cross-sectional extent was measured at the cerebral peduncle level. Wallerian degeneration was detected in 99 patients (57.6%). The area of T2 high intensity was significantly correlated with Brunnstrom stage. Multiple regression analysis showed that the upper extremity stage contributed most to the visualization of Wallerian degeneration. This is partly because the pyramidal tract participates in fine and precise movement. The extent of the area of Wallerian degeneration is found to be helpful in making a prognosis with respect to motor impairment in the upper extremity. PMID- 1600188 TI - The use of functional electrical stimulation to assist gait in patients with incomplete spinal cord injury. AB - The use of FES (functional electrical stimulation) for gait reproduction in six patients with spinal cord injury is described. Following a detailed neuromuscular assessment the patients commenced a muscle conditioning programme using electrical stimulation applied via surface electrodes. Once patients were strong enough to stand, gait synthesis was initiated in the laboratory utilizing a programmable electrical stimulator. When a satisfactory gait pattern had been achieved, patients used their portable stimulator at home. All six patients became able to stand and walk using the FES system and completed the home phase of the programme. Three patients continue to use the system at home for exercise and walking; the other patients have discontinued using the system, preferring a wheelchair or their original orthoses. We conclude that FES-assisted walking is feasible in patients with incomplete spinal cord injury, even with severe motor loss. Further advances in technology are needed for the system to become applicable to a larger number of patients. PMID- 1600189 TI - Outcome of prosthetic management of bilateral lower-limb amputees. AB - This study was designed to evaluate the outcome in 41 bilateral lower-limb amputees admitted to an inpatient unit for prosthetic rehabilitation. Outcome measures were obtained using a simple activities of daily living score, the Frenchay Activities Index, mobility grading, and assessment of home adaptations. Though excellent success rates were obtained after completion of physiotherapy, the majority of the above-knee amputees had abandoned their prostheses by the time of review. Bilateral below-knee amputees, however, continued to do well regarding their prosthetic mobility, and prosthesis users were more independent in their activities of daily living. We believe that inpatient rehabilitation programmes for bilateral amputees are likely to prove more satisfactory than prolonged outpatient physiotherapy. PMID- 1600190 TI - Immunochemical and biological analysis of pheromone biosynthesis activating neuropeptide in Heliothis peltigera. AB - This study describes the preparation and characterization of a highly specific antiserum to Helicoverpa zea pheromone biosynthesis activating neuropeptide (Hez PBAN), and the use of this antiserum, in an enzyme linked immunosorbent assay (ELISA), to determine: a) the content of endogenous PBAN in head extracts of male and female Heliothis peltigera; b) the level of PBAN at different developmental stages; and c) the content of PBAN in four different moth species. Cross reactivity studies revealed that the antiserum is directed mainly toward the N terminal region of the neuropeptide, and that it exhibits similar binding affinities toward the oxidized and reduced forms of PBAN. Analysis of PBAN content in head extracts of male and female H. peltigera, at scotophase, revealed the presence of 4.97 and 4.58 pmol, respectively, in 3-day-old moths, and 5.33 and 4.78 pmol, respectively, in 7-day-old moths. The similarity in the content of PBAN at both ages and sexes was in accordance with the amount of pheromonotropic activity in these extracts which stimulated pheromone biosynthesis to a similar level. Analysis of PBAN-like immunoreactivity (IR) in head extracts of H. peltigera larvae and pupae demonstrated the existence of the neuropeptide in the 4th larval instar and continued to increase as a function of development. No IR could be detected in the first three larval instars. The larval and pupal extracts also exerted pheromonotropic activity which followed a similar pattern. The activity in these extracts, however, was considerably lower than that found in adult male and female heads. IR was also detected in head extracts of three other Noctuidae moths: Helicoverpa armigera, Cornutiplusia circumflexa and Spodoptera littoralis, indicating a high degree of chemical and structural similarity of PBAN in these moths. PMID- 1600191 TI - Studies on the enzymes involved in puparial cuticle sclerotization in Drosophila melanogaster. AB - The properties of cuticular enzymes involved in sclerotization of Drosophila melanogaster puparium were examined. The cuticle-bound phenoloxidase from the white puparium exhibited a pH optimum of 6.5 in phosphate buffer and oxidized a variety of catecholic substrates such as 4-methylcatechol, N-beta-alanyldopamine, dopa, dopamine, N-acetyldopamine, catechol, norepinephrine, 3,4 dihydroxyphenylglycol, 3,4-dihydroxybenzoic acid, and 3,4-dihydroxyphenylacetic acid. Phenoloxidase inhibitors such as potassium cyanide and sodium fluoride inhibited the enzyme activity drastically, but phenylthiourea showed marginal inhibition only. This result, coupled with the fact that syringaldazine served as the substrate for the insoluble enzyme, confirmed that cuticular phenoloxidase is of the "laccase" type. In addition, we also examined the mode of synthesis of the sclerotizing precursor, 1,2-dehydro-N-acetyldopamine. Our results indicate that this catecholamine derivative is biosynthesized from N-acetyldopamine through the intermediate formation of N-acetyldopamine quinone and N-acetyldopamine quinone methide as established for Sarcophaga bullata [Saul, S. and Sugumaran, M., F.E.B.S. Letters 251, 69-73 (1989)]. Accordingly, successful solubilization and fractionation of cuticular enzymes involved in the introduction of a double bond in the side chain of N-acetyldopamine indicated that they included o diphenoloxidase, 4-alkyl-o-quinone:p-quinone methide isomerase, and N acetyldopamine quinone methide:dehydro N-acetyldopamine isomerase and not any side chain desaturase. PMID- 1600192 TI - Detection of Helicobacter pylori-like organisms in the stomach of some food source animals using a monoclonal antibody. AB - To investigate a possible animal reservoir of Helicobacter pylori, 15 pigs, 15 rabbits and 5 cows slaughtered for consumption were studied. Raised serum IgG levels were found in 93% of the pigs and 87% of the rabbits, but levels were normal in the cattle. In the controlled testings three of 22 humans had elevated IgG to H pylori and in all three H pylori was detected by the use of monoclonal antibody. Helicobacter pylori were identified in gastric brushings by a monoclonal antibody in 8 out of 10 pigs and 7 out of 10 rabbits. This study suggests an animal reservoir of Helicobacter pylori which may be of importance in human infection. PMID- 1600193 TI - Simultaneous measurement of gastric emptying of digestible and indigestible solids in healthy humans. AB - Gastric emptying of digestible and indigestible solids has been simultaneously evaluated in healthy humans. Gastric emptying of indigestible solids occurs simultaneously during the emptying of digestible solids. The knowledge of the mechanism responsible for gastric emptying of both digestible and indigestible solids may contribute to improve physiologic insight in this field and to develop further clinical applications. PMID- 1600194 TI - Diagnosing and treating opportunistic infections of the oesophagus in AIDS patients. AB - The acquired immunodeficiency syndrome (AIDS) has created new problems in many areas of medicine. One of the most frequent gastrointestinal clinical manifestations of the disease is dysphagia/odynophagia which occurs in over 50% of patients at any stage of the illness and may severely compromise, if untreated, the nutritional status of the patient. In most cases it is due to an infection of the oesophagus by opportunistic pathogens (fungi or viruses or both) and may be successfully treated, at least temporarily, by specific drugs. This article reviews the most recent acquisitions in terms of diagnosis and treatment of such common problems in patients with AIDS. PMID- 1600195 TI - Neurally mediated effects of metoclopramide on pigeon oesophageal muscle. AB - The effects induced by metoclopramide (MCP) were examined in transverse muscular strips from pigeon oesophagus. MCP (0.1 nM-10 microM) induced a concentration dependent excitatory effect on the EMG activity, characterized mainly by an increase in the spike burst frequency. Such an excitatory effect was fully antagonized by tetrodotoxin and partially antagonized by atropine, by naloxone and by desensitization of the preparation to 5-hydroxytryptamine (5-HT). The atropine-resistant excitatory component was not modified by guanethidine. The combination of naloxone and atropine was more effective than a single antagonist in blocking the response to MCP. The combination of naloxone and 5-HT desensitization failed to further reduce the MCP-induced excitatory effect. The present results indicate that the excitatory effects of MCP are mediated via neural elements. MCP activates both cholinergic and non-cholinergic, non adrenergic excitatory neurons. Furthermore, results suggest that serotoninergic and opioid neural pathways might be involved in the excitatory effects of MCP. PMID- 1600197 TI - Endoscopy of blastocystosis (Zierdt-Garavelli disease). PMID- 1600196 TI - Treatment of chronic hepatitis B with beta interferon given intramuscularly: a pilot study. AB - In a pilot study aimed to test the therapeutic potential of beta interferon (IFN) given intramuscularly we treated 4 patients with HBeAg positive chronic hepatitis B with a progressively increased dosage of beta IFN (from 5 to 9 million units daily) for 1 month and with 9 million units for 5 additional months, thrice weekly. In 3 of the 4 patients, serum HBV-DNA decreased during therapy and remained undetectable in 2 who seroconverted from HBeAg to anti-HBe while in 1 patient viraemia rebounded to pretreatment levels during the follow-up. In the remaining patient serum HBV-DNA fluctuated during treatment. These results suggest that beta IFN given intramuscularly has a potential therapeutic efficacy in patients with chronic hepatitis B and prompt further clinical trials in a larger number of patients. PMID- 1600198 TI - Recent advances on hydrogen metabolism in man. PMID- 1600199 TI - Co2- and H2 breath tests in the diagnosis of intestinal malabsorption. PMID- 1600200 TI - Malignancy following surgery for benign peptic disease: a review. AB - Since 1986 there have been a number of large studies of cancer risk after surgery for benign disease involving over 20,000 patients followed for at least 20 years. All show that gastric surgery carries an excess risk of gastric cancer after a 15 20 year latency. There is less agreement about the excess risk at other sites. The size of such risks appears to depend on the size of cohort, type of ulcer, type of surgery, length of follow-up and level of analytical detail. Statistically significant excess risks have been reported for cancer of the colon (6/8 studies), biliary tract (4/5), lung (6/6), bladder (3/3), pancreas (4/7) and all sites (2/3). Our own study showed an excess risk of cancer of the gallbladder (14.3 fold), stomach (4.5), breast (4.0), bronchus (3.9), large bowel (1.6), oesophagus (2.3), pancreas (4.0), bladder (2.4) and all sites (3.3). PMID- 1600202 TI - Digestive endoscopy is an integral part of gastroenterology. PMID- 1600201 TI - The role of gastroenterologists and digestive surgeons in ultrasonography. PMID- 1600203 TI - Endoscopy in the context of a full gastroenterological service. PMID- 1600204 TI - "R Farini" 1992-1993 Fellowship Award. PMID- 1600205 TI - [A study on work and daily life factors affecting the health of taxi drivers]. AB - In order to elucidate factors affecting taxi drivers health, a questionnaire survey was performed on 5523 taxi drivers and health examinations were conducted on 311 taxi drivers from among them. Analysis by a method of multivariate analysis called Quantification II was performed with dependent variables being blood pressure, the number of subjective symptoms and fatigue on rising, and independent variables being work and daily life conditions. The major results of this survey were as follows: 1) A tendency for hypertension risk to increase with degree of obesity, and both employment as a taxi driver for 1-4 years and over twenty years of taxi driving were positively associated with increase in risk for hypertension. 2) Common factors to all types of work shifts which were related to an increase in the number of subjective symptoms were irregularity of meals, insufficient rest on off days, large number of years engagement at taxi driving, frequent frightening experiences while driving and comparatively short driving distance in one shift. 3) Common factors to all types of work shifts that were connected with fatigue at the time of rising were insufficient rest on off days and long years engagement in taxi driving. PMID- 1600206 TI - [Four-year follow-up study of self-rated health and life satisfaction among caregivers]. AB - Changes in self-rated health and life satisfaction among caregivers of elderly and factors associated with the changes during a four year were investigated. The sample in the baseline survey consisted of persons randomly selected from recipients of welfare allowances for disabled elderly in two communities in Tokyo. A total of 152 persons were identified as living at home at the time of the first survey and 94 persons were surveyed. In a follow-up survey after a 4 year interval, 73 persons were followed. The main results were as follows: 1. Of the 73 original caregivers, 28 persons continued to give care, and 45 stopped caregiving activities. 2. Among those persons who had been cared for by the 45 caregivers who reported stopping care giving activities, 41 had died and 4 were placed in nursing homes or hospitals. Of the elderly who had died, 60% had been admitted to hospitals, with deterioration of the elderly persons' health being the biggest reason for hospitalization. 3. No significant changes in either self rated health or life satisfaction were seen after the 4-year interval in those caregivers who continued giving care. Persons who terminated caregiving had an increase in self-rated health in comparison with the original survey. 4. Where self-rated health declined among those continuing giving care, the decrease was related to decrease of cognitive ability of the elderly. A decrease of cognitive ability of the elderly, and also low social support and negative perception regarding caring for the elderly at the baseline survey, was associated with reduction in life satisfaction. 5. Among 45 subjects who terminated caregiving, persons who had low economic backgrounds at baseline, had low improvement of life satisfaction. Persons who did not have jobs had increase in self-rated health. PMID- 1600207 TI - [Analysis of the fertility decline in Japan--focusing on the period of 1950-60 and 1975-85]. AB - Marked fertility declines have been observed in Japan from 1950-60 and 1975-85. The dynamic structure of the fertility decline in the two periods was analyzed employing the Standardization Approach and Bongaarts Model of Proximate Determinants Analysis. The results indicate that the fertility decline in 1950-60 was mainly caused by a drop in marital fertility due to the expanding diffusion of contraception practices and increases in induced abortion. Increased age at marriage cannot be discounted as a factor also. The fertility decline in 1975-85 was mostly caused by delay of marriage as well as a reduction in proportion of the reproductive population which is composed of a cohort born in 1960 or later. PMID- 1600208 TI - [Assessment of adaptation to on-board conditions on "The Ship for World Youth"]. AB - The adaptation process of youth from 13 countries on board "The 3rd Ship for World Youth" cruise which was held from January 18 to March 20 in 1991 was analyzed. The age of almost all of the participants was in the 20's (average age was 24.9 yrs), and there were 103 participants (47 males, 56 females) from Japan, 171 participants (86 males, 85 females) from North, Middle and South America, and Oceanian countries for total of 274 participants (133 males, 141 females). The living environment on board differed significantly from daily living conditions of the participants, particularly due to the need to communicate in a foreign language, and to live in harmony with different cultures in a confinement situation, such that they were inevitably susceptible to various stressors. Among the participants there were some who needed psychiatric care and treatment. In order to assess quantitatively psychosomatic reactions to those stressors, a 28 item scaled GHQ (= General Health Questionnaire) assessment was performed four times on board with the following findings: 1. Highest scores were seen shortly after embarkment and decreased as the participants got accustomed to the living conditions on board. 2. The scores of the Japanese participants were higher than those of foreign participants, possibly indicating awkward adaptational skill on the part of Japanese participants especially during the first stage. 3. Japanese females scored slightly higher than Japanese males throughout the course of the program. 4. No clear difference in scores between Japanese participants aged under 25 y and over 26 y was observed. 5. A large proportion (77.3%) of Japanese participants had Y-G personality test results classifying them in the 'stable positive' group (D group). These participants had significantly lower scaled GHQ scores than those in the non-D group, indicating a high adaptational ability of D group participants. PMID- 1600209 TI - [Monthly variation of viable count and coliforms count of sandpits in parks]. AB - Field and experimental microbiological investigations of samples from sandpits from 5 parks were performed 2 times a month for 1 year, January-December 1990. Total viable count from the sandpits was highest in the surface layer sample than the inner layer throughout the year. However, there was no such tendency in the number of Coliforms and Enterobacter, Escherichia coli, Citrobacter. The number of bacteria on the surface and inner layer was high from April to June, and in September and October, while it was low in July and August. The proportion of Coliform bacteria represented in the total viable count ranged from 2.1 to 8.9% in the surface layer and from 1.6 to 19.6% in the inner layer. There was a significant correlation between the numbers of bacteria on the surface and inner layer. Relationships between the total viable count and Coliform count and between Coliform count and E. coli, Enterobacter and Citrobacter were also observed. In view of the results it can be concluded that park sandpits are not, from a hygienic point of view, to be an ideal environment for children to play in. PMID- 1600210 TI - [An investigation on health conditions of South American workers of Japanese parentage]. PMID- 1600211 TI - [Some problems at the detection of Escherichia coli in well waters by the use of beta-glucuronidase activity]. PMID- 1600212 TI - Comparison of two digitally programmable hearing aids. AB - The purpose of this project was to compare the Widex Quattro and the Ensoniq Sound Selector hearing instruments as to benefits (real and perceived) and overall convenience. It is the premise of the Ensoniq designers that a high fidelity (wide band) hearing aid is adequate for all listening conditions due to its exact reproduction of sound. Conversely, it is the premise of the Quattro designers that a hearing aid user needs access to multiple frequency responses (memories) for optimal benefit in different communicative situations. Subjective measures showed little differentiation between the two instruments, except for the Ease of Communication subtest of the Profile of Hearing Aid Performance (PHAP). New users rated the Quattro as performing better, while experienced users rated the Ensoniq significantly better. Objective measures indicated some differences in the performance of the two instruments, although these results may be related to the fitting strategies employed. PMID- 1600213 TI - The effect of equating loudness on audibility-based hearing aid selection procedures. AB - Recently the articulation index (AI) has received a great deal of attention as a means to select hearing aid characteristics and to evaluate the merits of different hearing aid selection methods. These evaluations were based on the seldom modified assumption that the listening condition producing the largest AI is the best condition. The negative consequences of the differences in hearing aid conditions were seldom considered. In this paper it is shown that higher AIs are often achieved at the cost of substantially greater loudness. When gain adjustments are made to equate loudness across conditions, very different conclusions are reached about the relative merits of selection methods and the value of certain frequency-gain response modifications. PMID- 1600214 TI - Adaptive procedures for hearing aid prescription and other audiologic applications. AB - A class of adaptive procedures is described. These procedures are relatively easy to implement and have many useful properties for audiologic applications. Recent advances in programmable hearing aids enable these techniques to be used effectively in adaptive prescriptive fitting of a hearing aid. All of the procedures are based on the simple up-down technique that, in addition to its simplicity, is both efficient and reliable. PMID- 1600216 TI - Advances in earmold technology: one-stage (direct) approach. AB - Many hearing aid users require a customized earmold. When the hearing impairment is severe or profound, it is essential that a good fit of the earmold is achieved to avoid leakage of sound and acoustic feedback (whistling) so that the full potential of the hearing aid can be achieved. Existing laboratory technology for the production of earmolds by a two-stage process leads to dimensional inaccuracy because of (1) unsuitable materials that shrink and (2) techniques used to achieve a surface finish. Recently, a novel soft material, from which an accurate earmold can be fabricated by a one-stage process directly in the ear, has been invented by the author and patented by the United Kingdom Department of Health. This paper describes the new technology, which could provide very significant benefits in the rapid fabrication of accurate earmolds without requiring sophisticated laboratory facilities. In addition, important implications for very young infants, the profoundly deaf, and for earmold use in developing countries will be discussed. PMID- 1600215 TI - Behavioral assessment of CID's benchtop (version 2) digital hearing aid: noise reduction. AB - Perceptual rating and word identification procedures were used to evaluate the efficacy of several digital hearing aid adaptive and nonadaptive noise reduction algorithm parameters. The study included 15 hearing-impaired adults listening to speech at soft, moderate, and loud input levels in quiet, fan noise, and multitalker babble noise. The results suggest that hearing-impaired listeners can make clarity judgments that result in the selection of algorithms that optimize word intelligibility at soft and moderate speech levels. The spectral adaptation requirements, however, were not constant with signal level. PMID- 1600217 TI - Application of digital signal processing to hearing aids: a critical survey. AB - An audiologic rationale for the application of digital signal processing techniques to hearing aids is developed. These techniques enable complex processing beyond that possible in presently available analog aids. A critical survey of algorithms for filtering, nonlinear processing, noise reduction, speech enhancement, and feedback reduction is presented. The paper concludes with a discussion of practical considerations for implementation. PMID- 1600218 TI - Key issues in hearing aid selection and evaluation. AB - This article examines three key issues in hearing aid selection and evaluation. First, two studies are analyzed to determine the extent to which differences in frequency response characteristics result in differences in judgments of the intelligibility or pleasantness of amplified speech. Small to moderate frequency response differences usually did result in different judgments although occasionally large differences did not. When two dissimilar responses are equally intelligible, it is likely that the best response is something in between them. Second, evidence indicates that it is not always satisfactory to allow frequency response to be determined by prescribing gain at each frequency separately. This suggests, therefore, that separate frequency response prescription rules are needed. Third, signal audibility is discussed in the context of using simplified Articulation Index schemes to predict aided performance. It is demonstrated how wrong conclusions may easily be drawn in the absence of accurate knowledge of the signal levels received when different hearing aid options are used. Data suggest that the Articulation Index may not be applicable to steeply sloping high frequency hearing losses. This needs further investigation before the Articulation Index can be recommended for hearing aid evaluations. PMID- 1600219 TI - Hearing aid saturation, coherence, and aided loudness discomfort. AB - Real-ear measurements of the aided Loudness Discomfort Level (LDL) were obtained from five hearing-impaired listeners who were fit with two Class A and two Class D linear hearing aids, each with a different saturation sound pressure level (HFA SSPL90). These measurements were obtained with 75 dB SPL continuous discourse to determine whether saturation-induced distortion contributes to the sensation of loudness. Real-ear coherence measurements made at LDL were used to determine the extent of saturation, and sound quality judgments were used to determine whether the distortion present at LDL affected sound quality. Results indicated that the SPL, coherence, and sound quality ratings obtained at LDL were all higher for Class D hearing aids with relatively high HFA SSPL90 than for Class A hearing aids with relatively low HFA SSPL90. Overall results were generally consistent with the hypothesis that distortion affects both sound quality and the perception of loudness. PMID- 1600220 TI - Prescriptive hearing aid fitting by parameter adjustment and selection. AB - We describe the rationale for the development of a psychophysical procedure that allows individual listeners to adjust the frequency-gain characteristic of a programmable hearing aid on a unidimensional scale, based on a target-gain reference value. The listener's task is to adjust the frequency response and select the parametric value judged to optimize the intelligibility or quality of speech. Originally described as the Sliding Scale, the procedure has been modified for use in reliability and validity studies of hearing aid fitting at Michigan State University. The modified approach is referred to as the Parameter Adjustment and Selection (PAS) procedure. Primary immediate goals for the procedure are ease of use, high reliability, and rapid clinical administration. The procedure, which may offer potential advantages over a paired-comparison approach, appears to be generally applicable to the fitting of digitally programmable hearing aids. PMID- 1600221 TI - Relations between Anopheles darlingi breeding habitats, rainfall, river level and malaria transmission rates in the rain forest of Suriname. AB - Irregular peaks of P.falciparum malaria incidence were monitored in Suriname during 1982-86. An attempt is made to correlate these fluctuations of malaria rates with rainfall and river level in relation to the periodic availability of breeding habitats for the malaria vector Anopheles darlingi Root. Densities of adult female An.darlingi were recorded in the Upper-Marowijne region of Suriname, in a focus of malaria along the Marowijne River. Peaks in biting densities correlated well with periods of (i) high water level in the long rainy season, (ii) low water level in the long dry season, and (iii) abundant rainfall in the short rainy season. Critical levels of river-height and rainfall were defined which could explain most of the monthly fluctuations in malaria parasite incidence observed in this area. PMID- 1600222 TI - The New World screwworm fly in Libya: a review of its introduction and eradication. AB - The New World screwworm fly, Cochliomyia hominivorax (Coquerel) (Diptera: Calliphoridae), became established in the Old World for the first time during 1988, in the Socialist People's Libyan Arab Jamahiriya. An obligate parasite of mammals in its larval stages, causing wound myiasis, it is one of the most serious insect pests of livestock in the Americas. To avert a major disaster for the livestock industry and wildlife of Africa and southern Europe, the Libyan Government and the Food and Agriculture Organization of the United Nations launched a massive screwworm eradication programme, based on the sterile insect technique, SIT. An initial containment operation involved veterinary teams working in the infested area (25,000 km2 around Tripoli), regularly inspecting livestock and, if necessary, treating them with insecticide. Quarantine stations were also set up, to prevent the movement of infested livestock out of the area. Sterile flies from the Mexican-American Commission for Eradication of Screwworms were first released in December 1990 at the rate of 3.5 million per week. This built up to 40 million per week by May 1991. The release of sterile flies was terminated on 17 October 1991, 6 months after the last detected case of screwworm myiasis in Libya. Intensive surveillance and quarantine activities will, however, continue through 1992. During 1992 the Libyan Government should be able to officially declare the New World screwworm eradicated from Libya, making it one of the most important success stories of pest control. PMID- 1600223 TI - Identification of members of the Simulium ochraceum species complex in the three onchocerciasis foci in Mexico. AB - Larval collections of Simulium ochraceum Walker (Diptera: Simuliidae) were made in a variety of streams in the three onchocerciasis foci in Mexico and identified by cytotaxonomic criteria, based on the banding pattern of polytene chromosomes in larval salivary gland nucleii. S. ochraceum cytotype A was found in the Soconusco focus, cytotype B in the Oaxaca focus and cytotype C (not previously recorded in Mexico) in the Chamula focus. Attempts to analyse chromosomes of adult specimens were unsuccessful. A preliminary study of the cuticular hydrocarbons of adult specimens by gas liquid chromatography provided evidence that this technique may be suitable for separating the cytotypes. PMID- 1600224 TI - Population genetic evidence for species A, B, C and D of the Anopheles dirus complex in Thailand and enzyme electromorphs for their identification. AB - Mixtures of chromosomal forms A, B, C and D in natural populations of Anopheles dirus Peyton & Harrison sensu lato in Thailand show significant positive values of Wright's fixation index for six enzyme-electromorph loci. The mean value of FIS over all loci was found to be +0.28 (SD 0.02), with a range of +0.57 (Odh) to +0.10 (Idh-2). Partitioning electromorph data for the chromosomal forms reduces the mean FIS to 0.03 (SD 0.01), which suggests that positive assortative mating is a characteristic of each form. This supports the hypothesis that the chromosomal/electrophoretic forms A, B, C and D represent four distinct biological species within the An. dirus complex. An example is given of the use of enzyme electromorphs as a means of vector identification during a malaria entomological field study involving a mixture of An. dirus species A and D. Electromorph identifications of 323 sp. A and 161 sp. D were more than 98% correct when cross-referenced to specific DNA probes. PMID- 1600225 TI - Isozyme variability and differentiation between Rhodnius prolixus, R.robustus and R.pictipes, vectors of Chagas disease in Venezuela. AB - Enzyme polymorphism in triatomine bugs of the genus Rhodnius (Hemiptera: Reduviidae), vectors of Chagas disease, is analysed using both starch and polyacrylamide gel electrophoresis. Out of forty-five enzymes assayed, the electromorphs of seventeen of them: AO, CA, DIA, ES, ES-A, FH, GPD, G6PD, GPI, MDH, ME, 6PGD, PGM, ACON, ACPH, LAP and SOD, involving twenty-two putative structural loci, were scorable. These gene-enzyme systems were therefore selected for routine characterization of R.prolixus Stal adults from different strains. The first thirteen enzymes, involving sixteen structural loci, were also analysed in first instar nymphs of the three species, R.prolixus, R.robustus Larrousse and R.pictipes Stal. Allelic frequencies were calculated for three R.prolixus strains: three to five loci appeared to be polymorphic. The proportion of polymorphic loci (22%) and the average heterozygosity (0.06) indicated low genetic variability, with significant differences between the strains at individual loci. Rhodnius prolixus and R.robustus were found to have identical isozymic patterns. R.pictipes was genetically well differentiated, with twelve diagnostic loci. PMID- 1600226 TI - Efficacy of Esbiothrin mosquito coils at community level in northern Tanzania. AB - Field trials with mosquito coils containing 0.15% Esbiothrin at Usa River settlement, northern Tanzania, during 1986 achieved a 52% reduction in biting rates of Anopheles arabiensis Patton and a 73% reduction of Culex quinquefasciatus Say mosquitoes. No mosquito biting activity occurred during the coil burning period which started at 20.00 hours daily and lasted for an average of 8.6 h. A sociological survey indicated that the coils were favourably accepted and produced no serious side-effects. PMID- 1600227 TI - Comparative activity of three repellents against the ticks Rhipicephalus sanguineus and Argas persicus. AB - The residual repellent activity of N,N-diethylphenyl-acetamide (DEPA), N,N diethyl-3-methyl benzamide (DEET) and dimethylphthalate (DMP) against the hard tick Rhipicephalus sanguineus (Latreille) and the soft tick Argas persicus (Oken) from topical application on rabbits and hens respectively in the laboratory have been studied. It was found that a 25% concentration of DEET gave strong repellency (greater than 90%) against larvae and nymphs of R. sanguineus for 15 and 7 days respectively and against A. persicus larvae and nymphs greater than 90% for 11 and 5 days respectively. Strong repellency (greater than 90%) against adults of the hard and soft ticks was observed for 9 and 7 days respectively with 40% DEET. DEPA at 25% concentration showed strong repellency (greater than 90%) against larvae and nymphs of R. sanguineus and A. persicus for 11 and 5 days respectively. Adults of hard and soft ticks were strongly repelled (greater than 90%) for 9 and 5 days respectively by 40% DEPA. DMP was found to be the least effective against all stages of both species of tick. PMID- 1600228 TI - Dispersive flight by Triatoma infestans under natural climatic conditions in Argentina. AB - Male and female T. infestans were released on two consecutive nights in the salinas of Cordoba Province, Argentina, when air temperatures during the flying period averaged 28.5 degrees C. 136 males (43% of the total released) and 170 females (57%) flew on the first night, and 6 males (18%) and 7 females (27%) on the second. Of these, we recovered 23 males and 14 females within 100 m, and a further female within 200 m, all from the first night's release. The remainder appear to have flown more than 100 m and possibly more than 200 m. In support of this conclusion 4 male and 5 female bugs were recovered in an abandoned brick house 550 m from the release point. Since the proportion of bugs apparently flying more than 200 m is considerably greater than that deduced from previous experiments at lower temperatures (Lehane & Schofield, 1981) it is possible that temperature influences not only the proportion of bugs flying but also the distance flown. Flight appears to be affected by wind speed. On the first night, when there was negligible wind, 43% of male and 57% of female bugs flew. On the second night, with winds gusting at 4-5 m/s, only 18% of the male and 27% of the female bugs flew. PMID- 1600229 TI - Probing behaviour and sporozoite delivery by Anopheles stephensi infected with Plasmodium berghei. AB - We observed that Plasmodium berghei sporozoite-infected Anopheles stephensi was not impaired in its ability to locate blood on a host. When probing rats, infected mosquitoes took as long as non-infected mosquitoes to locate blood. Contrary to previous suggestions, infective mosquitoes delivered sporozoites into mineral oil even after extensively probing a vertebrate host. We observed that, in mosquitoes having probed a host, both the mean number of sporozoites ejected over 3 min into oil (35.9 v. 31.7 sporozoites) and the proportion of mosquitoes delivering sporozoites (60% v. 50%) were similar to mosquitoes not having probed. We then developed a model of sporozoite delivery, taking into account observations that sporozoites are clumped in the lumen of the glands as well as upon delivery, and that output is uneven and inconsistent. We conclude that clumping optimizes transmission, if a threshold of infection exists and the mean number of sporozoites per clump is greater than the threshold. PMID- 1600230 TI - Biological response of German cockroaches fed diets containing allopurinol. AB - The acceptability of dietary allopurinol to German cockroaches, Blattella germanica (L.), was assessed. In diet choice tests between rat chow with or without 0.1% w/w allopurinol there were no significant differences in nymphal development, feeding duration, visits or consumption. The LT50 of cockroaches fed a choice of diets was 3 weeks greater (7.88) than those fed non-choice a 0.1% allopurinol diet. Female cockroaches provided a choice of diets aborted a significantly greater percentage of their oothecae (98.6%) than those fed the untreated diet (1.7%). Choice arena tests of 2% allopurinol in rat chow significantly reduced cockroach populations compared with untreated controls. After 6 weeks, populations were reduced by approximately 50%, and 97% after 14 weeks. These results indicate that allopurinol is acceptable to B. germanica as a dietary supplement which could be used in baits for cockroach control. PMID- 1600233 TI - Y-chromosome dimorphism in the malaria vector Anopheles stephensi from south India. PMID- 1600232 TI - Determinants of the domiciliary density of Triatoma infestans, vector of Chagas disease. AB - In two heavily infested rural villages of Santiago del Estero, Argentina, where no indoor-spraying with residual insecticides had ever been carried out by official control services, we studied the influence of roof and wall structure, domestic use of insecticide, family size and the number of domestic dogs, on the domiciliary density of Triatoma infestans (Klug). Bug density was significantly associated with (1) the interaction between insecticide use and type of roof, (2) the structure of indoor walls, (3) the number of dogs sharing sleeping areas of people (room-mate dogs), and (4) the number of people plus room-mate dogs, but not with just the number of people resident in the house. The interaction between insecticide use and a roof made of 'simbol', a locally available grass (Pennisetum sp.), also reflected a younger age structure of domestic bug populations. In infested houses, the density of bugs infected with Trypanosoma cruzi Chagas was significantly correlated with overall bug density. Our data suggest that the application of environmental management measures by the affected people, such as plastering of walls and modification of roofs, coupled with keeping dogs away from bedrooms and application of insecticides, should limit the domestic population density of T. infestans and thus reduce the transmission of T. cruzi to people. PMID- 1600231 TI - Development of an attractive target for the sheep blowfly Lucilia sericata. AB - Coloured, odour-baited, sticky targets, designed to catch the sheep blowfly Lucilia sericata Meigen are described and the results of field trials are presented. The number of L. sericata caught by the targets was positively related to target surface area and was dependent on target colour. The performance of the coloured targets is described by a model in which catch is related negatively to reflectivity in the 300-450 nm (ultra-violet/blue) band of the spectrum and positively to the reflectivity in the 450-580 nm (blue-green-yellow) band. Of the Lucilia blowflies caught by the targets, 13-16% were L.sericata and 72-75% of the L.sericata were female. The number of L.sericata caught appeared to be positively related to the availability of sheep over a relatively localized area and showed a marked decline following insecticidal dipping of sheep. The further development of targets and the implications of the results for L.sericata control are discussed. PMID- 1600234 TI - Selection of the yellow fever mosquito Aedes aegypti for cheap and easy maintenance without bloodmeals. PMID- 1600235 TI - Biological control of Culicidae with the copepod Mesocyclops aspericornis and larvivorous fish (Poeciliidae) in a village of French Polynesia. AB - The copepod Mesocyclops aspericornis Daday and the larvivorous fishes Gambusia affinis (B. & G.) and Poecilia reticulata R. & B., were released into mosquito breeding sites in Tuherahera village, Tikehau atoll, French Polynesia, to control larvae of Aedes aegypti (L.), Ae.polynesiensis Marks, Culex annulirostris Skuse and Cx quinquefasciatus Say. Treatments were completed within a week, in January 1990. Fish quickly eliminated mosquito larvae from the open breeding sites (ponds, wells). The impact of copepods in water tanks, drums and covered wells was inconsistent, apparently depending on the availability of microfaunal diet for growth of copepod nauplii. As the biting rate of adult Ae.aegypti seemed to be unaffected by the biological control of larvae, this village-scale experiment was judged to be unsuccessful as a means of vector control. PMID- 1600236 TI - Resistance to tomato spotted wilt virus infection in transgenic tobacco expressing the viral nucleocapsid gene. AB - A recombinant plasmid containing the entire tomato spotted with virus (TSWV) nucleocapsid gene, with the exception of nucleotide encoding three N-terminal amino acids, was isolated by screening a complementary DNA library, prepared against random primed viral RNA, using a specific monoclonal antibody. The insert contained in plasmid pTSW1 was repaired and amplified by polymerase chain reaction, and the complete nucleocapsid protein gene was introduced into Nicotiana tabacum 'Samsun' by leaf disk transformation using Agrobacterium tumefaciens. Transgenic plants expressing the viral nucleocapsid protein were resistant to subsequent infection following mechanical inoculation with TSWV as indicated by a lack of systemic symptoms and little or no systemic accumulation of virus as determined by double antibody sandwich enzyme-liked immunosorbent assay. These results further extend the applicability of coat protein-mediated resistance, as previously demonstrated for a number of simple plant viruses composed of a positive-sense RNA genome encapsidated with a single species of coat protein, to a membrane-encapsidated, multi-component, negative-sense RNA virus. PMID- 1600237 TI - Effect of a virus on accumulation of a tissue-specific cell-surface protein of the fungus Cryphonectria (Endothia) parasitica. AB - Hypovirulence and decreased sporulation of the plant pathogenic fungus Cryphonectria (Endothia) parasitica is caused by double-stranded (ds)RNAs. These symptoms of dsRNA infection are correlated with down-regulation of at least nine major fungal polypeptides. One of the regulated polypeptides was purified to homogeneity and antibody to it was prepared. This polypeptide (cryparin) has a glycine-serine-repeating sequence near the amino-terminal end that is typical of structural proteins and has properties of a lectin. Antibody-staining showed that this 18.6-kDa polypeptide is specific to aerial hyphae and fruiting bodies and that it accumulates in large amounts on hyphal cell surfaces. The dsRNA affects accumulation of this protein, both in the fugal hyphae and in the growth medium. Cryparin is similar in physical properties to those of the putative phytotoxin cerato-ulmin produced by the Dutch elm disease fungus. Toxicity of cryparin is not detectable, but the striking similarities between the physical properties and locations of accumulation of cryparin and cerato-ulmin in fungal fruiting structures suggest either conservation of structure or convergent evolution in function of these two proteins. PMID- 1600238 TI - Detection and separation of Rhizobium and Bradyrhizobium Nod metabolites using thin-layer chromatography. AB - Using radioactive acetate as a precursor, it was shown that the common nodABC genes of Rhizobium and Bradyrhizobium strains are involved in the production of one or more metabolites that are excreted into the growth medium. A rapid thin layer chromatography (TLC) system has been developed to separate these so-called Nod metabolites that can then be visualized by autoradiography. Different patterns of Nod metabolites were observed in the tested strains of the cross inoculation groups of R. leguminosarum bv. viceae, R. l. bv. trifolii, R. meliloti, and B. japonicum. Only Nod metabolites of R. meliloti became labeled when radioactive sulphate was present in the medium. The role of the other nodulation genes of R. l. bv. viceae in the production of the detected Nod metabolites was tested in further detail. In addition to the common nodABC genes, the nodFE and nodL genes are involved in the production of Nod metabolites. In contrast, the chromosomal background did not influence the number of detected Nod metabolites or their mobilities on TLC plates. Nod metabolites could also be produced and excreted in Escherichia coli cells in which the appropriate nodulation genes were expressed. PMID- 1600239 TI - cDNA cloning, structure and expression of a novel pathogenesis-related protein in bean. AB - We have isolated cDNA clones spanning the full length of a transcript (PvPR3) encoding a novel pathogenesis-related (PR) protein in bean (Phaseolus vulgaris). The PvPR3 transcript accumulates gradually over 24 hr in elicitor-treated cell suspensions. This pattern of expression is distinct from those of previously reported elicitor-induced transcripts in bean. Specifically, transcripts encoding two recently described acidic bean PR proteins, phenylpropanoid pathway enzymes, accumulate to maximal levels by 4-8 hr, while hydroxyproline-rich glycoprotein mRNA accumulation is delayed by several hours. The PvPR3 mRNA also accumulates after wounding of hypocotyls with kinetics comparable to those of mRNA encoding phenylpropanoid pathway mRNAs. PvPR3 appears to exist as a single gene within a family of approximately 15 related genes in the bean genome. The PvPR3 protein deduced from the cDNA sequences (14,950 Da pI = 10.0) lacks a putative signal peptide suggesting a cytosolic localization. Amino acid sequence comparisons with databases revealed that PvPR3 represents a new class of PR proteins without significant sequence homology to previously characterized PR proteins or other proteins. PMID- 1600240 TI - The cellular basis of the convergence and extension of the Xenopus neural plate. AB - There is great interest in the patterning and morphogenesis of the vertebrate nervous system, but the morphogenetic movements involved in early neural development and their underlying cellular mechanisms are poorly understood. This paper describes the cellular basis of the early neural morphogenesis of Xenopus laevis. The results have important implications for neural induction. Mapping the fate map of the midneurula (Eagleson and Harris: J. Neurobiol. 21:427-440, 1990) back to the early gastrula with time-lapse video recording demonstrates that the prospective hindbrain and spinal cord are initially very wide and very short, and thus at the beginning of gastrulation all their precursor cells lie within a few cell diameters of the inducing mesoderm. In the midgastrula, the prospective hindbrain and spinal cord undergo very strong convergence and extension movements in two phases: In the first phase they primarily undergo thinning in the radial direction and lengthening (extension) in the animal-vegetal direction, and the second phase is characterized primarily by mediolateral narrowing (convergence) and anterior-posterior lengthening (extension). These movements also occur in sandwich explants of the gastrula, thus demonstrating the local autonomy of the forces producing them. Tracing cell movements with fluorescein dextran-labeled cells in embryos or explants shows that the initial thinning and extension occurs by radial intercalation of deep cells to form fewer layers of greater area, all of which is expressed as increased length. The subsequent convergence and extension occurs by mediolateral intercalation of deep cells to form a longer, narrower array. These results establish that a similar if not identical sequence of radial and mediolateral cell intercalations underlie convergence and extension of the neural and the mesoderm tissues (Wilson and Keller: Development, 112:289 300, 1991). Moreover, these results establish that radial and mediolateral intercalation are the principal neural cell behaviors induced by the planar signals emanating from the dorsal involuting marginal zone (the Spemann organizer) in the early gastrula (Keller et al: Develop. Dynamics, 193: 218-234, 1992). Radial and mediolateral intercalation are induced among the 5 to 7 rows of cells comprising the prospective hindbrain and spinal cord, thus producing the massive convergence and extension movements that narrow and elongate these regions of the nervous system in the late gastrula. A more general significance of these results is that neural induction is best analyzed and understood in terms of the dynamics of the morphogenetic processes involved. PMID- 1600241 TI - Planar induction of convergence and extension of the neural plate by the organizer of Xenopus. AB - This paper demonstrates that convergence and extension within the neural plate of Xenopus laevis are regulated by planar inductive interactions with the adjacent Spemann organizer. The companion article (Keller et al.: Developmental Dynamics 193:199-217, 1992) showed that the prospective hindbrain and spinal cord occupy a very short and very wide area just above the Spemann organizer in the early gastrula and that these regions converge and extend greatly during gastrulation and neurulation, using a sequence of radial and mediolateral cell intercalations. In this article, we show that "planar" contact of these regions with the organizer at their vegetal edge until stage 11 is sufficient to induce convergence and extension, after which their convergence and extension become autonomous. Grafts of the organizer in planar contact with uninduced ectodermal tissues induce these ectodermal tissues to converge and extend by a planar inductive signal from the organizer. Labeling of the inducing or responding tissues confirms that only planar interactions occur. Neural convergence and extension are actually hindered in explants deliberately constructed so that vertical interactions occur. These results show unambiguously that the Spemann organizer induces the extraordinary and precocious convergence and extension movements of the Xenopus neural plate by planar interactions acting over short distances. PMID- 1600242 TI - Mesoderm movement and fate during avian gastrulation and neurulation. AB - Quail/chick transplantation chimeras were constructed during stages of gastrulation and neurulation to follow the subsequent movement and fate of cells of the primitive streak. All grafts were placed solely within the confines of the primitive streak to prevent confusion between cells that had not yet ingressed and those that had already ingressed, and transplanted cells were distinguished from host cells on the basis of a naturally occurring cell marker. Pathways of movement of ingressing cells corresponded to their level of residence within the primitive streak. Cells residing within Hensen's node (the cranial end of the primitive streak) initially migrated mainly cranially, remaining on or near the midline, and then extended caudally along the midline as regression of Hensen's node occurred. Cells residing within the nodus posterior (the caudal end of the primitive streak) migrated caudally. Cells residing at levels of the primitive streak between Hensen's node and the nodus posterior typically migrated bilaterally, confirming that such cells had not already ingressed prior to their transplantation (in which case, they would have migrated unilaterally). Subsets of these cells residing at progressively more caudal levels of the primitive streak migrated incrementally more laterally. Hensen's node contributed cells to the gut endoderm, head mesenchyme, notochord, and median hinge-point (MHP) cells of the neural tube (future floor plate). At younger stages (i.e., stages 3a, 3b) Hensen's node contributed cells to principally the foregut endoderm and head mesenchyme, whereas at older stages (i.e., stages 3c, 3d, 4), it contributed cells to principally the notochord and MHP region. The remaining segments of the cranial half of the primitive streak contributed cells to the various mesodermal subdivisions of the embryo, and the lengths of the segments forming these subdivisions were estimated. The most cranial level of the streak (directly behind Hensen's node) contributed cells to the most medial mesodermal subdivisions (head mesenchyme, somites) and consecutively more caudal levels of the streak contributed cells to sequentially more lateral mesodermal subdivisions (intermediate mesoderm, lateral plate mesoderm). The caudal half of the primitive streak contributed cells to the extraembryonic mesoderm, with the nodus posterior contributing to the most caudal extraembryonic mesoderm, including the blood islands. Our results confirm and extend the previous avian prospective fate maps, increasing our understanding of the movement and fate of cells of the gastrula and neurula stages. PMID- 1600243 TI - Positional control of mesoderm movement and fate during avian gastrulation and neurulation. AB - Segments of primitive streak from donor quail embryos at stages of gastrulation and neurulation were transplanted heterotopically and isochronically to primitive streaks of host chick embryos. The subsequent movement and fate of grafted cells was determined using the quail nucleolar marker to define grafted cells. The pattern of movement of grafted cells depended on their new position within the primitive streak, not on their original position. When cells of cranial regions were placed more caudally, they moved to mesodermal subdivisions that were located lateral to those they would have populated if left in their original position. When caudal segments were placed more cranially, they moved to more medial mesodermal subdivisions. Whether the fate of grafted cells corresponded to their original location or their new location depended on both their level of origin and their new position. Cells from heterotopically transplanted Hensen's nodes, which migrated to the somitic and more lateral mesoderm, self differentiated notochords. Similarly, in some cases, heterotopically transplanted prospective somitic cells, which migrated to lateral plate mesoderm, formed ectopic somites. In other cases, however, grafted cells contributed to the host's somites, intermediate mesoderm, and lateral plate mesoderm. Moreover, prospective somitic cells, which migrated to the extraembryonic lateral plate mesoderm, changed their fate and formed extraembryonic lateral plate mesoderm; and prospective lateral plate mesoderm cells, which migrated to the somitic mesoderm, formed somites as well as intermediate mesoderm and lateral plate mesoderm.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600244 TI - Expression of sarcomeric myosin in the presumptive myocardium of chicken embryos occurs within six hours of myocyte commitment. AB - The distribution of sarcomeric myosin heavy chain (MyHC) has been examined immunocytochemically in the presumptive myocardial cells of chicken embryos (stages 6-10) prior to the onset of the heart beat. Embryos were stained with monoclonal antibody MF20, a reagent which recognizes all chicken sarcomeric MyHCs (Bader et al., 1982), and then examined both in whole mount by immunofluorescence and in semithin, plastic-embedded sections following immunoperoxidase labeling. We observed that myosin could be detected as early as stage 7 (0-2 pairs of somites) in 29% of the 31 embryos examined, and by stage 8 (4 pairs of somites) more than 80% of the embryos were MF20+. Every embryo with 5 pairs of somites (stage 8+) labeled strongly with MF20. Labeling was first detected at stage 7 to 7+ as a diffuse fluorescent signal within pleomorphic cells of the splanchnic mesoderm located in two crescent-shaped regions bordering each side of the anterior intestinal portal (AIP). With progressive development, the two crescent shaped regions merged at the apex of the AIP, and as the two heart tubes began fusion at stage 9, the MyHC+ regions extended cranially and medially. By somite stages 9-10, the myosin-positive cells completely encircled the heart tube. From stages 7 to 9 the myosin signal had no sarcomeric distribution; i.e., there were no MyHC striations nor periodic repeats evident in the presumptive myocytes until late stage 9 and stage 10. Semithin sections revealed that myosin was first distributed in apical regions of the myocytes, adjacent to the pericardial coelom. The implications of these findings for myocyte determination, differentiation and morphogenesis are discussed. PMID- 1600245 TI - Cartilage matrix protein is a component of the collagen fibril of cartilage. PMID- 1600246 TI - The influence of bone and marrow on cartilage hypertrophy and degradation during 30-day serum-free culture of the embryonic chick tibia. AB - In this study, an organ culture system is defined which demonstrates complete loss of cartilage matrix from embryonic chick tibiae. Efficient loss of the cartilage matrix occurs within 30 days of serum-free culture only when the intact tibiae containing bone, marrow, and cartilage tissue are cultured. During organ culture nonhypertrophic chondrocytes become hypertrophic and stain positively for type X collagen and alkaline phosphatase. The cartilage loses Safranin O staining, and finally all cartilage matrix disappears leaving the bony collar and marrow cells. If the tibial cartilage is separated from the bony collar and cultured alone in serum-free medium, the nonhypertrophic chondrocytes also hypertrophy; the matrix loses Safranin O staining; however, some components of the matrix including type X collagen still remain after 30 days. In the presence of serum, the chondrocytes will hypertrophy but cartilage degradation is not evident. The results of this study support the conclusions that 1) hypertrophy is inherently programmed in the chondrocyte and 2) while Safranin O staining of cartilage cultured alone is diminished in serum-free organ culture, the degradation of cartilage is complete only when bone and marrow are also present. PMID- 1600247 TI - Retinoic acid-induced change in anteroposterior positional identity in regenerating axolotl limbs is dose-dependent. AB - Retinoic acid (RA) induces pattern duplication in the proximodistal (PD) axis of axolotl limb regenerates. The effect is dose-dependent, with the maximum extent of duplication being evoked at a dose of 150 micrograms RA/g body weight. The same dose of RA induces maximum pattern completion in the anteroposterior (AP) axis of regenerating anterior half or double anterior half limbs. RA inhibits the regeneration of posterior half or double posterior half limbs (Kim, W.S., and Stocum, D.L. [1986] Dev Biol 114:170-179). The effects of lower doses of RA on the AP axis of limb regenerates have not been tested and thus it is not known whether the effects of RA on positional identity in this axis are dose-dependent or are all-or-none. To answer this question, we examined the effects of a range of doses of RA on AP positional identity in regenerating double anterior and double posterior axolotl forelimbs and hindlimbs constructed by exchanging the anterior and posterior halves of right and left zeugopodia as either autografts or homografts. Ten days after the exchange, the double half zeugopodia were amputated through their distal ends. At 4 days postamputation, the animals were injected intraperitoneally with 20, 50, 75, or 100 micrograms RA/g body weight and the constructs allowed to regenerate for at least 6 weeks. Control double anterior forelimbs and hindlimbs formed symmetrical regenerates with an average of two and 1.8 anterior digits, respectively. RA treatment induced the blastema of double anterior zeugopodia to regenerate missing posterior structures in mirror-image patterns and to duplicate zeugopodial and stylopodial elements in the PD axis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600248 TI - Schistosomiasis. PMID- 1600249 TI - The language of epidemiology. (X). Relative and attributable risk. PMID- 1600250 TI - A brief history of schistosomiasis. PMID- 1600251 TI - Clinical schistosomiasis. PMID- 1600252 TI - Nutritional status and child growth in schistosomiasis. PMID- 1600253 TI - Cytokines, hepatic fibrosis and schistosomiasis. PMID- 1600254 TI - Modern approaches to development of vaccines against schistosomes. AB - Vaccination, as currently practiced, is a prophylactic procedure. A vaccine is given before exposure to the infectious agent, in order to induce a state of specific immunological memory within the recipient. PMID- 1600255 TI - The hemoglobinase of Schistosoma mansoni. PMID- 1600256 TI - Chemotherapy of schistosomiasis. PMID- 1600257 TI - A look ahead in research and control of schistosomiasis. PMID- 1600258 TI - Dipyridamole electrocardiography test for the detection of severe coronary artery stenoses. AB - To investigate the relationship between dipyridamole-induced ST depression and the severity of coronary artery stenosis, the dipyridamole injection test (D) at 0.568 mg/kg/4 min, and the symptom limited treadmill exercise test (T) were performed separately in 16 normal volunteers and 167 patients who underwent coronary arteriography [91 patients without myocardial infarction (non-MI group) and 76 patients with previous myocardial infarction (MI group)]. Standard 12-lead electrocardiogram and body surface mapping of 87 leads were recorded in both tests. None of the normal volunteers had significant ST depression (greater than or equal to 0.10 mV) in D or T. Regarding the non-MI group, D had as high an incidence of ST depression as T (83% vs 93%) in patients with maximal coronary stenosis greater than or equal to 90%, while in those with maximum coronary stenosis less than 90%, D had a lower incidence of ST depression than T (16% vs 48%, p less than 0.01). For the MI group, the incidence of ST depression was compared to the maximal coronary artery stenosis supplying the non-infarcted area. In patients with maximal coronary artery stenosis greater than or equal to 90%, D had as high an incidence of ST depression as T (71% vs 64%). While, D had a lower incidence of ST depression than T (19% vs 35%, p less than 0.05) in those with maximum coronary artery stenosis less than 90%. For the diagnosis of coronary artery stenosis of greater than or equal to 90%, D had as high sensitivity (non-MI group, 82% vs 93%; MI group, 71% vs 64%) and higher specificity (non-MI group, 84% vs 52%, p less than 0.01; MI group, 81% vs 65%, p less than 0.05) compared with T. This study demonstrated that dipyridamole ECG is a sensitive and specific test to detect severe coronary artery stenosis. PMID- 1600259 TI - The cellular infiltrate in the liver of patients with fulminant hepatitis: analysis of paraffin-embedded tissue sections. AB - Intrahepatic infiltrate from 18 patients who died of fulminant hepatitis, was analyzed by an immunohistochemical method using formalin-fixed, paraffin-embedded liver sections and monoclonal antibodies. Inflammatory cells were characteristically located in the portal and periportal areas adjoining resting hepatocytes, but were infrequently found in the perivenular areas where hemorrhagic hepatocyte necrosis predominated. In the inflammatory infiltrate, T cells were the most predominant cell type, composing about two-thirds of the total hepatic infiltrate, followed by lysozyme-positive macrophages which composed about one-third of the total hepatic infiltrate, irrespective of the etiology of the fulminant hepatitis. On the other hand, B cells made up less than 2% in all cases, and plasma cells were also few, less than 2% in 12 of 18 cases. Furthermore, an enhanced display of beta 2-microglobulin on hepatocyte membranes was demonstrated in all cases with remaining hepatocytes, indicating an increased expression of class I MHC antigens on these cells. These results suggest that T cells may play an important role in the pathogenesis of the portal and periportal lesions of fulminant hepatitis, probably with a help of MHC class I antigens on hepatocytes, while hemorrhagic necrosis of hepatocytes around the central veins may be caused by a different mechanism, most likely a circulatory disturbance secondary to cell-mediated immune reactions in the periportal areas. PMID- 1600260 TI - Ultrasonographic evaluation of neck and supraclavicular lymph nodes metastasized from lung cancer. AB - The significance of ultrasonography in the evaluation of metastasized neck and supraclavicular lymph nodes from lung cancer was analyzed. By ultrasonography, the lymph nodes could be visualized clearly as low-echogenic round areas, and the size could be precisely measured in three dimensions. It was also possible to diagnose whether or not the lymph node adhered to the surrounding tissues and to determine the relationship and the connection of supraclavicular lymph node and upper mediastinal lymph node. The therapeutic effect related to the size of the lymph node was evaluable by ultrasonography. Therefore, the ultrasonographic approach to the neck and supraclavicular lymph nodes metastasized from lung cancer is considered to be useful for clinical use. PMID- 1600261 TI - Crossover trial comparison of enalapril maleate and trichlormethiazide in the treatment of essential hypertension: emphasis on the quality of life. AB - Enalapril and trichlormethiazide were compared with respect to effects on the quality of life in a crossover study of 36 patients with hypertension. Multiple choice 34-item questionnaires with three possible answers (severe, mild and none) per question were used to assess symptoms and mood. Twenty patients were initially given enalapril and 16 were initially given trichlormethiazide. There was no significant difference in the antihypertensive efficacy of the 2 drugs. Treatment with enalapril resulted in significant improvement in 11 of the 34 items, and a tendency for another 4 items to improve. Treatment with trichlormethiazide resulted in significant improvement in only 5 items and a tendency to improve in 2. When enalapril and trichlormethiazide were compared, significantly greater improvement in 2 items and a tendency toward greater improvement in 4 items was seen with enalapril treatment. Thus, enalapril was found to be more efficacious than trichlormethiazide with respect to quality of life in patients with hypertension. PMID- 1600262 TI - Analysis of cases of central nervous system fungal infections reported in Japan between January 1979 and June 1989. AB - Data from 129 cases of central nervous systemic fungal infections reported in Japan between January 1979 and June 1989 were analyzed. Of 129 cases, 116 were cryptococcal meningitis, 6 candidal meningitis (including meningitis due to Trichosporon cutaneum) and 7 Aspergillus meningoencephalitis. Fifty-six of the patients with cryptococcal meningitis had an underlying systemic disease or condition. The overall survival rate was 72.4%, which was a markedly improved rate compared to earlier reports. Cryptococcal meningitis was treated most often with the combination of intravenous amphotericin B and 5-fluorocytosine and was associated with a survival rate of 81.8%. All 7 patients treated with fluconazole alone survived. Candidal meningitis occurred secondary to a shunt infection; some patients with candidemia did well when adequate therapy was instituted. Aspergillus meningoencephalitis is most often diagnosed at autopsy or in surgical specimens and the prognosis of Aspergillus meningoencephalitis is generally poor. PMID- 1600263 TI - Comparative study of magnetic resonance imaging, computed tomography and histology in the assessment of liver iron overload. AB - Magnetic resonance imaging, computed tomography, and liver biopsy findings were compared in ten patients with serum ferritin levels over 500 ng/ml. The liver was observed as a low-intensity area on magnetic resonance imaging in all four patients with serum ferritin levels above 2,000 ng/ml, while no abnormalities were detected in four of the six patients with a serum ferritin level below 2,000 ng/ml. Computed tomography revealed the liver to be a high density area in five of the seven patients tested. However, it demonstrated no abnormality in a patient with steatosis despite a high serum ferritin concentration. Liver biopsy demonstrated iron deposits in nine of the ten patients. These findings indicate that liver biopsy remains the most accurate mean of detection of liver iron overload. Both magnetic resonance imaging and computed tomography could be used to be monitor the progress of a patient with liver iron overload treated by phlebotomy. PMID- 1600264 TI - Chest roentgenogram classification and clinical parameters in patients with active pulmonary tuberculosis. AB - The relationship between the clinical parameters and chest film appearance was studied in patients with active pulmonary tuberculosis. Patients with extended disease were often malnourished and had weak tuberculin reaction accompanied by lymphopenia. They excreted a large amount of mycobacterial bacilli and a longer period was required for negative conversion of sputum culture. We confirmed that the criteria for chest roentgenogram classification established by the Japanese Society for Tuberculosis ("Gakkai Classification") is useful in the estimation of the risk of infection and the prognosis of tuberculosis patients. PMID- 1600266 TI - Distribution and clinical significance of lupus anticoagulant and anticardiolipin antibody in 349 patients with systemic lupus erythematosus. AB - Samples from 349 patients with systemic lupus erythematosus (SLE) were tested simultaneously for lupus anticoagulant (LAC) and anticardiolipin antibodies (ACL). LAC was detected in 27.2% of 349 SLE patients by a modified mixing kaolin clotting time. ACL was detected in 34.7% by enzyme-linked immunosorbent assay. Only half of the patients who had LAC or ACL were positive for both of them. In addition, isotypes of ACL in these patients were studied. The IgG isotype was detected in 81.8% of 121 patients, and more than half had only the IgG isotype. When clinical features of patients with LAC or ACL were studied, the incidence of thrombosis, fetal loss, and thrombocytopenia were significantly higher in both groups compared with patients without LAC or ACL. In particular, the patients with both LAC and ACL showed the highest risk of fetal loss (89%) during pregnancy. These results indicate that LAC and ACL are detected in partly different groups of SLE patients, but both of these groups are clinically similar. PMID- 1600265 TI - Abnormalities of pulmonary function in patients with non-insulin-dependent diabetes mellitus. AB - To examine the possible association between the vascular complications of diabetes and changes in pulmonary function, we performed pulmonary function tests including assessment of the diffusing capacity (%DLco) in 80 patients with non insulin-dependent diabetes mellitus (45 males and 35 females) without overt lung or heart disease. The mean age of the subjects was 57.9 years and the mean duration of diabetes was 10.8 years. The %DLco decreased significantly as the duration of diabetes increased (r = -0.38, p less than 0.01), and the same relationship was also observed in non-smoking subjects (N = 37). The reduction in %DLco was greater in patients with diabetic microangiopathy (especially nephropathy) and in those treated with insulin. Other pulmonary function tests (%VC, FEV1.0, PaO2 and PaCO2) showed no relationship to the duration of diabetes, the degree of microangiopathy or the type of treatment. These results suggest that diabetic microangiopathy may play an important role in the decrease of %DLco. PMID- 1600267 TI - Exacerbation of hypothyroidism following tumor necrosis factor-alpha infusion. AB - A 46-year-old woman with chronic thyroiditis who had been receiving thyroid hormone treatment for 10 yr developed severe hypothyroidism (FT4 0.37 ng/dl, FT3 1.38 pg/ml, TSH 151.00 microU/ml) following tumor necrosis factor-alpha (TNF) infusion for the treatment of a complicated cutaneous T-cell lymphoma. Indirect immunofluorescence staining of thyroid follicular cells showed aberrant expression of HLA class II antigens. The mechanisms underlying the exacerbation of the hypothyroidism may be an augmentation of immunological processes in the thyroid and a direct action of TNF on the synthesis and secretion of thyroid hormone. PMID- 1600268 TI - Truncal hypesthesia in patients with Minamata disease. AB - Patients with Minamata disease (methylmercury intoxication) usually suffer from the glove and stocking type hypesthesia in the extremities. Recently it is believed that the sensory disturbance of the disease may be a manifestation of the cerebral involvement. The aim of this study was to determine the pain threshold of their extremities and body by algesimeter. The results showed that a majority of the patients had elevated pain thresholds in the body and the extremities, and suggest that the pain impairment is not responsible for the peripheral nerve involvement. PMID- 1600269 TI - Two fatal cases of hepatitis B virus carriers after corticosteroid therapy for bronchial asthma. AB - We report two hepatitis B virus (HBV) carriers who had liver failure after withdrawal of corticosteroids (steroids) administered for treatment of serious asthmatic attacks. Liver functions deteriorated 1 to 2 wk after withdrawal of the steroid therapy and liver failure occurred. Steroid readministration and intensive therapy for liver failure did not prevent death. An excessive immune response provoked by steroid withdrawal and decreased reserve capacity due to underlying chronic liver disease were thought to be factors in the liver failure. Caution must be exercised in the administration of steroids to patients with underlying chronic HBV infection to prevent exacerbation of hepatitis. Prompt readministration of steroids is indicated if evidence of liver failure develops. PMID- 1600270 TI - Two cases of acute myeloid leukemia evolving into a chronic myelomonocytic leukemia-like state after induction therapy. AB - Two patients with acute myeloid leukemia (AML) developed a chronic myelomonocytic leukemia (CMMoL)-like state after chemotherapy. Both patients showed morphological evidence of myelodysplasia together with acute leukemia at presentation (Case 1: M5b with trilineage myelodysplasia and Case 2: M4 with dysmegakaryocytopoiesis). They also showed persistent monocytosis without prominent blast cell proliferation after induction therapy. The possibility was suggested that these two patients were in acute transformation from CMMoL at presentation and returned to a CMMoL-like state after induction therapy. PMID- 1600271 TI - Intraventricular concealed double tachycardia: a case report. AB - An electrophysiologic study was performed on a patient with ischemic sustained ventricular tachycardia (VT). During pacing at the right ventricular apex, ventricular double potential was recorded at the left ventricular apex. Sustained VT was induced by double extra stimuli from the right ventricular apex. Three types of VTs with different QRS morphologies were observed, and each VT was changeable to other types. The interval between one of the two potentials and the surface QRS was constant during all VTs, but the other potential showed dissociation from the surface QRS. During this dissociation, an intrinsic rhythm of the potential was sometimes shorter than the cycle length of the VT. The mechanism of a block between the VT and a bystander could hardly explain these electrophysiologic findings. Concealed double ventricular tachycardia was considered to be the likely mechanism. PMID- 1600272 TI - An aged patient with Henoch-Schonlein purpura nephritis: a case report and review of the literature. AB - A 63-year-old patient with Henoch-Schonlein purpura (HSP) nephritis showed progressive proteinuria. Purpura was observed in the extremities as well as in the trunk without any preceding upper respiratory tract infections or drugs, and it disappeared after corticosteroid therapy although mild proteinuria continued throughout the therapy. Renal biopsy specimens showed mesangial IgA deposits in the glomeruli, but no IgA deposits were observed in the dermal vessels or in the intrarenal extraglomerular capillaries. Progressive proteinuria was improved with 37.5 mg/day of captopril. Severity of HSP nephritis in middle-aged to aged patients in the literature was reviewed. It was suggested that careful observation is required in aged patients with HSP nephritis. PMID- 1600273 TI - Progressive systemic sclerosis complicated with immune thrombocytopenia during D penicillamine therapy. AB - Immune thrombocytopenia is a rare complication of progressive systemic sclerosis (PSS). A 47-year-old female with PSS treated with D-penicillamine developed immune thrombocytopenia, which promptly responded to prednisolone and withdrawal of D-penicillamine. Platelet-associated IgG was elevated and the bone marrow megakaryocyte count was normal. There was an inverse relationship between the level of platelet-associated IgG and the platelet count. A lymphocyte stimulation test sensitized by D-penicillamine was positive. The present case suggests that immune thrombocytopenia may be regarded as one of the D-penicillamine-related immune abnormalities. To our knowledge, its association with PSS has never been reported. PMID- 1600274 TI - A case of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) with low plasma concentrations of antidiuretic hormone. AB - A 66-year-old Japanese man presented with persistent hyponatremia without polydipsia and polyuria. Laboratory examination showed serum sodium of 117 mEq/l, plasma osmolality 239 mosm/kg, urine sodium 108 mEq/l, urine osmolality 577 mosm/kg, and normal levels (less than 2.0 pg/ml) of serum antidiuretic hormone (ADH). ADH release was regulated normally with changes in plasma osmolality. No obvious cause for the syndrome of inappropriate secretion of ADH (SIADH) could be detected. However, 20 months later, the patient had bouts of hematuria and was found to have cancer of the urinary bladder. Increased renal sensitivity to ADH was suspected as the underlying mechanism of SIADH. PMID- 1600275 TI - Prevention of progressive renal failure by levothyroxine sodium in a diabetic patient with renal insufficiency and hypothyroidism. AB - The progressive renal failure of a 49-year-old female diabetic patient with renal insufficiency and hypothyroidism was successfully prevented by levothyroxine sodium treatment. Her renal function worsened in parallel with the exacerbation of hypothyroidism. Cessation of progressive renal failure was observed after administration of levothyroxine sodium (0.05 mg daily) for more than 24 months. Mean slopes of reciprocal serum creatinine levels for 12 months before and after the administration of levothyroxine sodium were -1.67 x 10(-3) and +8.68 x 10( 4), respectively. It was suggested that levothyroxine sodium was effective in the prevention of progressive renal failure in this patient. PMID- 1600276 TI - Gross ascites as a first manifestation of primary hypothyroidism due to post treatment of radioiodine therapy for Graves' disease. AB - We report herein a case with myxedema (primary hypothyroidism) associated with marked ascites that was found during the course of examination for a suspected decompensated state of liver cirrhosis or malignant disease. Aspirated ascitic fluid was found to have the characteristics of the exudate. Thyroid hormone replacement resulted in rapid clinical improvement with resolution of the ascites. This case is an unusual association of hypothyroidism as a cause of ascites. In all the cases with ascites of unknown etiology, the differential diagnosis requires consideration of myxedema. PMID- 1600277 TI - A case of primary leiomyosarcoma of the heart. AB - A 53-year-old male was hospitalized with complaints of cough, fever and backache. Two-dimensional echo-cardiography showed a pericardial echo-free space and a mass in the right atrium. Based on the MRI findings showing a pericardial mass originating from the atrial tumor, the final diagnosis of leiomyosarcoma was made by a percutaneous pericardial biopsy. Despite various therapies, the patient died after 3 wk. Because of its rareness (to date only 25 case reports), a premortem diagnosis of primary cardiac leiomyosarcoma is generally difficult. However, we feel that MRI and a subsequent biopsy is quite useful for making an early diagnosis of this disease. PMID- 1600278 TI - A case of beta-thalassemia with a C----T substitution at position 654 of the second intervening sequence of the beta-globin gene. AB - A 26-year-old Chinese-Malaysian female patient with beta-thalassemia is presented. The main hematological values found in this patient were as follows: 1) normocytic hypochromic anemia (RBC 444 x 10(4)/microliters, Hb 11.8 g/dl) with marked anisopoikilocytosis, 2) erythroid hyperplasia, and 3) increased HbF (HbA 41.4%, HbA2 2.9%, HbF 48.9%). DNA obtained from peripheral leukocytes was analyzed using dot blot hybridization of the polymerase chain reaction (PCR) amplified DNA with allele-specific oligonucleotide probes. A C----T substitution at position 654 of the second intervening sequence (IVS-2) was detected in her beta-globin clone. PMID- 1600279 TI - Aplastic anemia in a male with loss of the Y chromosome. AB - We carried out chromosomal analysis of a 33-year-old male who was diagnosed as having aplastic anemia. The patient showed severe pancytopenia, a normal NAP score, hypoplastic marrow and no myelodysplastic changes. 45,XO was found in all bone marrow cells examined, and in 10% of peripheral blood cells examined. To our knowledge, this is the first reported case of male aplastic anemia to show loss of the Y chromosome in all bone marrow cells examined, and this case may suggest a possible mechanism of juvenile onset of aplastic anemia. PMID- 1600280 TI - Bilateral Bochdalek hernias in an elderly patient diagnosed by magnetic resonance imaging. AB - An elderly patient with asymptomatic bilateral Bochdalek hernias is reported. The chest roentgenogram showed dome-shaped supradiaphragmatic masses about 6 cm in diameter in the posteromedial regions of both sides of the lungs. Computed tomography showed a discontinuity of the lines of diaphragmatic musculature in the left thorax, and a mass with a homogenous low density area indicative of fatty tissues in the right thorax. The magnetic resonance imaging, coronal and sagittal T1-weighted images revealed interruptions of the diaphragmatic musculature adjacent to the masses and protrusion of retroperitoneal fat into the thoracic cavity. The lesions were therefore diagnosed as bilateral Bochdalek hernias of the diaphragm. PMID- 1600281 TI - Sibling cases of primary biliary cirrhosis associated with polymyositis, vasculitis and Hashimoto's thyroiditis. AB - Primary biliary cirrhosis (PBC) was diagnosed in two siblings, a 42-year-old male and his 49-year-old sister. Furthermore, they were complicated with three types of autoimmune diseases: polymyositis, Hashimoto's thyroiditis and vasculitis of the right axillary artery. Although PBC is often associated with other autoimmune diseases, reports of the association with polymyositis and vasculitis syndrome are rare. Familial clustering of PBC with autoimmune diseases is also rare. PMID- 1600282 TI - Renal artery thrombosis in a patient with membranous glomerulonephritis. AB - A 64-year-old man with renal artery thrombosis (RAT) associated with nephrotic syndrome (NS) is reported. Although this patient was diagnosed as NS due to membranous glomerulonephritis (MGN) and treated with prednisolone, RAT occurred as a result of unknown mechanisms and caused mild renal dysfunction. Creatinine clearance has been about 70 ml/min for 9 years since the onset of RAT. The renal scintigraphic image has not changed since the onset. NS responded to prednisolone therapy initially and at the time of the relapse. Recent data have shown proteinuria levels of less than 0.2 g/day. PMID- 1600283 TI - A simple expression for quantifying bacterial chemotaxis using capillary assay data: application to the analysis of enhanced chemotactic responses from growth limited cultures. AB - An individual cell-based mathematical model of Rivero et al. provides a framework for determining values of the chemotactic sensitivity coefficient chi 0, an intrinsic cell population parameter that characterizes the chemotactic response of bacterial populations. This coefficient can theoretically relate the swimming behavior of individual cells to the resulting migration of a bacterial population. When this model is applied to the commonly used capillary assay, an approximate solution can be obtained for a particular range of chemotactic strengths yielding a very simple analytical expression for estimating the value of chi 0, [formula: see text] from measurements of cell accumulation in the capillary, N, when attractant uptake is negligible. A0 and A infinity are the dimensionless attractant concentrations initially present at the mouth of the capillary and far into the capillary, respectively, which are scaled by Kd, the effective dissociation constant for receptor-attractant binding. D is the attractant diffusivity, and mu is the cell random motility coefficient. NRM is the cell accumulation in the capillary in the absence of an attractant gradient, from which mu can be determined independently as mu = (pi/4t)(NRM/pi r2bc)2, with r the capillary tube radius and bc the bacterial density initially in the chamber. When attractant uptake is significant, a slightly more involved procedure requiring a simple numerical integration becomes necessary. As an example, we apply this approach to quantitatively characterize, in terms of the chemotactic sensitivity coefficient chi 0, data from Terracciano indicating enhanced chemotactic responses of Escherichia coli to galactose when cultured under growth-limiting galactose levels in a chemostat. PMID- 1600284 TI - Effects of time lags on transient characteristics of a nutrient cycling model. AB - A simple ecosystem with limiting nutrient cycling is modeled by chemostat equations with an integral term describing the continuous time lag involved in the process of nutrient regeneration from organic sediments. The same model has already been proposed in a previous paper, where conditions for boundedness of the solutions and stability of the equilibria were given. This paper is concerned with the relationships between resilience, that is, the speed with which the system returns to a stable equilibrium following a perturbation, and the time lag in the nutrient recycling process. Simple algorithms are given for the numerical calculation of the characteristic return time toward the stable equilibrium following a small perturbation. These methods also allow us to distinguish the case of monotone convergence from that of oscillatory convergence toward equilibrium. The numerical results obtained show that the presence of the time lag causes both qualitative and quantitative modifications in the dependence of equilibrium resilience on some relevant ecological parameters, such as the input nutrient concentration and the recycling extent. Analytical results for "quasi closed" ecosystems are given that show that such stable systems are characterized by a very low resilience. PMID- 1600285 TI - A parity-dependent immigration-birth-death-emigration process. AB - An immigration-birth-death-emigration process is studied when the immigration, birth, death, and emigration parameters depend on two parity classes of individuals, namely, zero and nonzero parity. The expected number of individuals in the population at time t and that of emigrants in (0,t) of both parity classes are obtained using the probability generating function (pgf) technique. The explicit expression for the pgf of the process is derived when the parameters are parity-independent. Population extinction and some limiting results are also discussed. PMID- 1600286 TI - Construction of linear invariants in phylogenetic inference. AB - An analytical method is presented for constructing linear invariants. All linear invariants of a k-species tree can be derived from those of (k-1)-species trees using this method. The new method is simpler than that of Cavender, which relies on numerical computations. Moreover, the new method provides a convenient tool to study the relationships between linear invariants of the same tree or of different trees. All linear invariants of trees of up to five species are derived in this study. For four species, there are 16 independent linear invariants for each of the three possible unrooted trees, 14 of which are shared by two unrooted trees and 12 of these are shared by all three unrooted trees; the last types of linear invariants can be used to construct tests on the assumptions about nucleotide substitutions. The number of linear invariants for a tree is found to increase rapidly with the number of species. PMID- 1600287 TI - Bifurcations and chaos in a time-discrete integral model of population dynamics. AB - The properties of a time-discrete integral model of population dynamics are studied. The model equations define a dynamic system in the cone of nonnegative functions in L2. The presence of dissipator caused by spatial interaction is detected. Several bifurcations of codimensions 1 and 2 are investigated. The model may go over to chaotic behavior through a sequence of period-doubling bifurcations. The Lyapunov exponents and dimension of an attractor are found. The higher dimension of an attractor is shown to be a common feature of chaotic behavior. PMID- 1600288 TI - [Epidemiologic progression of dementia diseases in Austria until the year 2050]. AB - Population projections of the Austrian Central Statistical Office show a dramatic increase of the proportion of people of 65 years of age and over in Austria until the year 2050. Since this population group is at higher risk to develop dementia, it will be necessary to suitably modify the presently available facilities for social and medical care to meet this increasing demand. Based on official demographic data and epidemiological findings of the "Eurodem"-group (12) our computations show that the number of demented persons, aged 65 or over, will rise from presently 80,000 to over 189,000 in 2050 (1990: 1,023/100,000, 2050: 2,509/100,000 persons of the total population), equivalent to an increase by 140%. By forecasting the number of persons affected, it should be possible to intensify (and in some areas introduce) long-term health planning in respect of aged people, dementia and social, financial and medical care in Austria. PMID- 1600289 TI - Regional variation in hospital admission rates in The Netherlands, Belgium, northern France, Nordrhein-Westfalen. AB - For the analysis of regional variations in hospital admission rates a model was set up, including both supply and demand indicators. Data were gathered for regions in four health care systems (the Dutch, Belgian, French and German), for 1982, 1979, 1974 (France 1982 only). Hospital bed supply proved to be the key factor in the explanation of the variation. The French health care system and, to a lesser extent, the German, turned out to be the strongest supply-dominated health care systems of the four. However, supply dominance in the German health care system seems to decrease over time. We concluded that the empirical generalisation, contained in Roemer's law, a bed built is a bed filled, is conditioned by time and place. Hypotheses on the conditional character of Roemer's law require further testing. PMID- 1600290 TI - [How can the vaccination status in Germany be improved?]. AB - Notwithstanding that the costs of health are comparatively high in the Federal Republic of Germany (FRG), the degree of immunisation against different infectious diseases in the population of the formerly FRG is really lower than in that of the former GDR or many other European countries. This fact may be due to the dualism of uncoordinated vaccinations by the Public Health Service on the one hand and be registered medical practitioners on the other. However, a rational strategy of vaccination should take into consideration that vaccination campaigns by the Public Health Service promise higher effectivity and lower costs than individual vaccinations by registered medical practitioners. Therefore, vaccination campaigns should be performed as much as possible by the Public Health Service whereas individual vaccinations should be given by registered medical practitioners only subsidiarely. PMID- 1600291 TI - [Health in school routine--an example of community health promotion in Berlin Steglitz]. AB - The sequel of a resolution of the West German Lander Ministries of Health in 1982 was the development of the Federal Health project Community-Oriented Health Education (1984-1989). This project was managed by the Federal Agency for Health Promotion in Cologne. Berlin-Steglitz is one of the Public Health offices involved in this project. A health-promoting cooperation between a primary school, the Public Health Service, the administration and the partners of a recently enacted Health Reform Law was initiated. This school project has been operating for the last 5 years. PMID- 1600292 TI - [Dental status of 12-year-old children]. AB - During the course of a stomatological screening 96% of all twelve-year old children in the district Greiz were examined with respect to the rate of dental caries and malocclusion and oral hygiene index. The results were compared with the targets of the WHO "Health for all by the year 2000". PMID- 1600293 TI - [Extent and structure of data in realization of lifelong epidemiologic surveillance]. AB - The realisation of a "medical record linkage" concept to achieve a lifelong medical surveillance requires the evaluation of the size and structure of the expected data. From this point of view the accessible health documentations of 120 persons of a small town covering the life period from birth to the age of 72 were evaluated retrospectively. The "epidemiological life report" resulting from this procedure enables the compilation of data on the reasons for utilising the health care system according to diagnostic-therapeutic and preventive aspects, and on the total number of medical expertises and paraclinical examinations. The number of data per person is considerable. In the course of a persons life he or she will come to the doctor for medical consultation about 600 times and will undergo 200 paraclinical examinations. A few aspects regarding the incidence of outpatient consultations are described in some detail. PMID- 1600294 TI - [Comment on the contribution by Schaefer, Schumacher and Zolondek, "Organization of environmental medicine ambulatory care/counseling sites in public health offices--a promising approach?"]. PMID- 1600296 TI - Breast feeding duration in consecutive offspring: a prospective study from southern Brazil. AB - The association between breast feeding duration in two consecutive pregnancies was studied in a prospective study in southern Brazil. In a population-based sample of 5960 women giving birth in 1982, 1386 delivered a second child within 4 years. The data were analyzed using life table techniques. The duration of breast feeding of the second child increased directly according to the duration the previous child had been breast fed. In particular, when the previous child had been breast fed for 6 months or more, the subsequent child was clearly more likely to be breast fed. However, when the previous child had been breast fed for under 6 months, the differences among subsequent children disappeared after 3-6 months. These differences were still present after stratification by family income, maternal education and parity. Mothers with a previous unsuccessful or problematic breast feeding experience should receive special priority in promotion campaigns. PMID- 1600295 TI - Longitudinal zinc balances in breast-fed and formula-fed infants. AB - Longitudinal zinc (Zn) balance studies were performed under domestic conditions in term breast-fed (n = 10), term formula-fed (n = 5; Zn concentration in the formula: 4 mg/l) and preterm formula-fed (n = 3) infants during the first 17 weeks of life. Samples of milk, urine and feces were analyzed by atomic absorption spectrometry. The median daily Zn intake in breast-fed infants decreased from 0.592 (0.457-0.829) mg Zn/kg body weight to 0.151 (0.095-0.304) mg Zn/kg body weight in the first 17 weeks of life; comparable values for bottle-fed term infants were 0.58 (0.511-0.701) and 0.674 (0.529-0.731) mg Zn/kg body weight. The median percent retention of Zn intake was 27 (-60 to 81.4)% in breast fed infants and 21.5 (-42 to 64)% in formula-fed infants. In view of the urinary and fecal Zn losses measured, a daily intake of 0.3-0.5 mg Zn/kg body weight is considered to be sufficient to ensure a Zn retention equivalent to breast-fed infants. This requires a Zn concentration of 2-3 mg/l of Zn depending on milk volume intake. PMID- 1600297 TI - Thermal responses and heart rates of low-birth-weight premature babies during daily care on a heated, water-filled mattress. AB - Body temperatures, heart rates and resting oxygen consumptions were examined during routine nursing care in 12 premature babies treated alternately in incubators or on a heated, water-filled mattress (HWM). The mean temperatures were significantly higher in the axilla (0.3 degree C; p less than or equal to 0.05) and the foot (1.4 degrees C; p less than 0.001) during HWM care. The degree of maximal fall in various body temperatures during routine nursing procedures was the same for both treatments, whereas the time taken for the foot temperature to fall was 13 min shorter during HWM care (p less than 0.001). The proportion of heart rates below 160 bpm when the babies were not disturbed was 7.4% greater during HWM treatment (p less than 0.01). The resting oxygen consumption in babies treated on HWM was slightly lower (6.2 +/- 0.4 vs 6.4 +/- 0.5 ml/kg/min; p less than 0.05). Treatment on the HWM seems to promote calm and comfort, since it reduces the amount of thermal stress and prolongs quiet resting periods. PMID- 1600298 TI - Familial history of cardiovascular disease and blood lipid pattern in newborn infants. AB - The levels of atherogenic lipid fractions are higher in children with a family history of ischemic cardiovascular disease (CD). This study was designed to examine this relationship in neonates. A total of 1276 newborns were investigated; 400 cord blood samples were collected for measurement of triglycerides (TG), total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C); on day 4, 1200 capillary samples were taken for TC and TG measurements. Male newborns with a positive history of CD had higher concentrations of cord blood TC (P less than 0.04) and LDL-C (P less than 0.02). On day 4 this difference in TC was no longer detectable (LDL-C not determined). A coronary heart disease (CHD) risk factor family history is sensitive (0.87) in predicting high cord blood concentrations of LDL-C, the specificity being 0.46 and the positive predicting value 0.08. PMID- 1600299 TI - Visual acuity and visual field development after cryocoagulation in infants with retinopathy of prematurity. AB - Visual development was studied in 10 very-low-birth-weight infants (less than 1500 g) with retinopathy of prematurity (ROP) stage 3+ who had been treated with cryocoagulation in both eyes. Binocular visual acuity (acuity cards method) and binocular visual fields (kinetic perimetry) were assessed repeatedly in the first year of life. At 12 months corrected age, visual acuity was normal in seven and impaired in three infants, who appeared to be severely myopic. Normal visual fields were found in eight infants at this age. The results indicate that cryotherapy in cases of ROP stage 3+ does not interfere with visual acuity development. The effect on visual field development needs further investigation. PMID- 1600300 TI - Giardiasis: haematological status and the absorption of vitamin B12 and folic acid. AB - The haematological status, as well as the fractional absorptions of folic acid (FAFol) and vitamin B12 (FAB12) were studied in 29 children aged 0.7-13.5 years (mean 3.3 years) with chronic diarrhoea due to giardiasis. Small intestinal biopsies revealed mucosal damage in 20 children; the biopsies of the remaining nine children were normal. At the initial investigation the FAFol and FAB12 values were below normal in approximately one-sixth and one-third of patients, respectively. Bacterial overgrowth of the small intestinal tract did not seem to play a role in FAB12 malabsorption. About one-fifth of patients had mild anaemia. None of the patients showed FAB12 insufficiency and only one patient suffered from folate depletion. At follow-up, FAFol, FAB12, haemoglobin and Erc-folate concentrations increased significantly while P-B12 and P-folate remained unchanged. Iron status, as well as dietary intake of iron, appeared insufficient prior to, as well as after treatment. Serum iron, transferrin saturation and haemoglobin concentrations were lower in patients who had acquired the disease abroad or suffered from persistent diarrhoea. PMID- 1600301 TI - Lidocaine for treatment of severe seizures in newborn infants. II. Blood concentrations of lidocaine and metabolites during intravenous infusion. AB - The blood concentrations of lidocaine and its main active metabolites, methylethylglycinexylidide (MEGX) and glycinexylidide (GX), were measured in 24 newborn infants during anticonvulsive treatment with an iv infusion of lidocaine. After a bolus dose of 1.5-2.2 mg/kg and continuous infusion of lidocaine (4.7-6.3 mg/kg/h) there was accumulation of the drug and MEGX within 24 h. After termination of the iv infusion, both lidocaine and the metabolites were eliminated within 24-48 h. The anticonvulsive effectiveness--estimated by clinical observation and continuous amplitude integrated EEG monitoring (cerebral function monitor)--was immediate in 15 infants (nine term and six preterm). There was no correlation between blood concentrations of lidocaine and metabolites, and anticonvulsive effect (i.e. good, intermediate or no response). No differences in blood concentrations were found between full-term and preterm babies, or between infants with or without birth asphyxia. In combination with a fast withdrawal of the drug, few adverse reactions were seen with the dosages used, even though blood concentrations were high. Routine measurements of lidocaine concentrations during anticonvulsive treatment in neonates seem to be of little clinical value. For evaluation of the anticonvulsive effect and for early detection of seizure activity during lidocaine withdrawal, continuous EEG monitoring is preferable. PMID- 1600302 TI - Characteristics and prognosis of hospital-treated obstructive bronchitis in children aged less than two years. AB - In a prospective study 101 children aged less than 2 years (median age 10 months), were examined the first time they were admitted to a paediatric ward for asthmatic symptoms. Two-thirds were boys and 58 had parents or siblings with allergic symptoms. During winter-spring, respiratory syncytial (RS) virus was verified in 50% of children. Other viral agents were adenovirus, parainfluenza 3, coxsackie B 2, ECHO 6 and rotavirus. At the acute stage, 54% of the children displayed changes on pulmonary X-ray. The total IgE value was greater than or equal to +2 SD score units in 14 children. At reinvestigation after 3-4.5 years, when the children were aged 3.3-6.3 years, 53% were free from asthmatic symptoms; the median age for the last episode was 2 years. A total of 33% had mild asthma, 8% moderate and 6% severe asthma. The factors which correlated significantly with persistent asthma were: (1) The need for daily medication for at least 6 months. (2) A young age in conjunction with the first wheezing episode and on the first admission to a paediatric ward because of asthmatic symptoms. (3) Other past or present atopic symptoms. Heredity, tobacco smoking at home, having a furry pet, RS virus infection, or high total IgE at the time of the first admission did not correlate significantly with the persistence of asthma 3-4.5 years later. The results emphasize the good overall prognosis of wheezing in early childhood, even when the wheezing is severe enough to lead to inpatient treatment. PMID- 1600303 TI - Dominant role for osmolality in the efficacy of glucose and glycine-containing oral rehydration solutions: studies in a rat model of secretory diarrhoea. AB - The effect of osmolality on the efficacy of oral rehydration solutions (ORS) and the contribution of the amino acid glycine to water absorption from ORS have been studied in an animal model of secretory diarrhoea. After exposure to pure cholera toxin, rat small intestine (excluding the duodenum) was perfused in situ with seven different ORS. All ORS were derived from a "basic" solution containing Na 50, K 25, Cl 75 and glucose 50 mmol/l to which 25 or 50 mmol/l of glycine, glucose, or mannitol was added. All ORS reversed water secretion to absorption, but maximum water absorption was obtained with the "basic" solution with an osmolality of 200 mOsm/kg. When the osmolality of the "basic" solution was raised to 225 and 250 mOsm/kg by adding mannitol, water absorption decreased. At each of these osmolalities, substitution of mannitol by glycine or glucose resulted in similar increases in water absorption, but all modifications compared unfavourably with the "basic" solution. Net sodium secretion occurred with all ORS tested, despite net water absorption. These findings in a perfusion model of rat small intestine suggest that osmolality is a key factor influencing the efficacy of ORS and that addition of a second substrate, such as glycine, has no beneficial effects. Our results suggest that there is a maximal rate for water absorption from the small intestine which is inversely related to the osmolality of the perfusate. PMID- 1600304 TI - Elevated short chain fatty acid concentrations in anaerobic small bowel contamination. AB - Viable bacteria were identified and counted, and short chain fatty acid concentrations measured in small intestinal fluid from 74 fasting children. In nine children with anaerobic small bowel contamination, individual and total short chain fatty acid concentrations were significantly higher than the remainder of the group (p less than 0.01). Using 100 mumol/l as the upper reference limit for total short chain fatty acid concentration, the sensitivity and specificity as a test for anaerobic small bowel contamination was 89% and 98%, respectively. Measuring luminal short chain fatty acid concentrations in proximal small intestinal fluid is an accurate method for detecting anaerobic small bowel contamination in children. PMID- 1600305 TI - Dyskinetic and dystonic cerebral palsy and birth. AB - Two hundred and nineteen cases of the dyskinetic and dystonic forms of cerebral palsy which were seen in the course of three decades at a single clinic have been analysed. Fifty-seven patients had kernicterus. In the remaining 162, 71% of whom were born at term, birthweight was below the expected mean in two-thirds. There was no relationship between birth weight, or abnormal birth, or asphyxia, and the ultimate clinical severity of the children. We conclude that abnormal birth and asphyxia are not direct causes of the cerebral damage, but are expressions of a pre-existing condition resulting in susceptibility to the stress of birth, whether it is normal or abnormal. PMID- 1600306 TI - Longitudinal anthropometric study in children with acute lymphoblastic leukaemia. AB - In four groups of patients with acute lymphoblastic leukaemia, anthropometric variables were investigated every 3 months for 2 years. Group 1 (n = 7) was treated with a high-risk protocol, group 2 (n = 13) with a standard-risk protocol including cranial irradiation, group 3 (n = 13) with a standard-risk protocol without cranial irradiation and group 4 (n = 8) was followed after completion of treatment. A height retardation of 0.4-0.6 SD was observed during therapy in groups 1-3. A catch-up of 0.5 SD was found in group 4. The retardation of armspan was significantly larger than the retardation of sitting height when groups 1-3 were taken together. Head circumference was not affected. The anthropometric variables reflecting nutritional status showed a growth above normal during and after treatment. Corticosteroid medication and not cranial irradiation is the most likely explanation for our findings. PMID- 1600307 TI - Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood. AB - In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment. PMID- 1600308 TI - Cholelithiasis during the first year of life: case reports and literature review. AB - Five cases are reported of children with gallstones diagnosed by ultrasound during their first 7 months of life. Of the four with symptomatic gallstones, one subsequently developed vitamin K deficiency syndrome with profuse bleedings. The children, who belonged to a defined population, were all diagnosed within an 18 month span, suggesting the frequency of early gallstone formation to be higher than formerly supposed. One child had haemolytic anaemia, but none of the conventional risk factors for stone formation was present in the other four cases. PMID- 1600309 TI - Food consumption and nutrient intake of one- to two-year-old Finnish children. AB - Food consumption data for 46, 1- to 2-year-old children in Helsinki were collected by means of 3-day food records. The mean daily energy intake was 1242 kcal for boys and 1092 kcal for girls. Protein accounted for 16% (range 9-24%), fat 33% (20-50%), total carbohydrates 51% (35-69%) and sucrose 12% (3-33%) of total energy intake. The mean ratio of polyunsaturated and saturated fatty acids was 0.43 (0.11-3.71). The average energy and nutrient intake met or exceeded the recommended amounts except for iron, zinc, fluorine and chromium. When the children were divided into four groups according to dietary fat content, the intake of several nutrients was lowest in the group with the highest fat content (40% or more of energy) even though energy intake did not differ. The wide variety observed, especially in the fat composition of the children's diets, indicates a need to reconsider the recommendations concerning the diet of young children after they have made the transition to family food. PMID- 1600310 TI - Glucose polymers in diarrhoea--risk of hypernatraemia. AB - An infant girl with congenital heart disease was fed glucose polymers as dietary supplements. During an attack of gastroenteritis with severe diarrhoea she developed hypernatraemic dehydration, probably due to the high osmotic load of the glucose polymers. This case illustrates the importance of giving adequate amounts of free water to a child on glucose polymers, especially during excessive fluid loss. PMID- 1600311 TI - Artificial renal and liver support in a severe hepatorenal syndrome of childhood. AB - This case report describes a special management approach in a child aged 4.5 years with a severe form of hepatorenal syndrome in which the final diagnosis was familial hemophagocytic lymphohistiocytosis (FHL). The patient presented with grade IV hepatic coma and acute renal failure (ARF). While the diagnosis was difficult at the time of admission, as well as during acute treatment, artificial liver support was established for elimination of bilirubin and other metabolic by products by using charcoal column plasma perfusion (CCPP) and bilirubin-adsorbing resin column plasma perfusion (BRCPP). Serum levels of bilirubin showed a notable decrease after each of the four treatment sessions. Additional artificial renal function replacement by continuous arteriovenous hemofiltration and hemodialysis (CAVH, CAVHD, respectively) had a marked lowering effect on urea and creatinine serum concentrations. Both artificial liver and renal support contributed to the general clinical improvement and survival of the patient. Further experience in these therapies will be needed to establish better prognosis in such fatal or acute similar conditions. PMID- 1600312 TI - Meningitis and midline facial deformity. AB - A baby with unilateral cleft lip, midline cleft palate and hypertelorism developed meningitis in the first 48 h of life. Examination of the nasopharynx showed a soft tissue mass, which was confirmed as a basal encephalocele by computed tomography. There was also congenital hydrocephalus and the corpus callosum was absent. Surgical treatment included repair of the anterior basal skull defect, repair of the lip and palate, and ventriculo-peritoneal shunt. There is currently evidence of developmental delay and right-sided visual impairment due to Morning Glory syndrome. This case demonstrates that basal encephalocele should be considered in any baby with midline facial deformity who develops meningitis. PMID- 1600313 TI - Long-term study of the immunodeficiency of Bloom's syndrome. AB - The immune state was evaluated over a 10-year period in two individuals with Bloom's syndrome. In both patients, serum concentrations of IgM were markedly low. Mildly decreased serum concentrations of IgG and IgA increased significantly with age, whereas the IgM levels remained low. From assessments of B-cell and T cell functions in pokeweed mitogen-induced immunoglobulin production, the IgM deficiencies were thought to result from B-cell dysfunction. T-cell function appeared intact. Moreover, although the percentages of surface IgM-bearing cells were not reduced, the numbers of IgM-secreting cells were reduced. These findings suggest that the IgM deficiency is due to an abnormality in the maturation of surface IgM-bearing B cells into IgM-secreting cells. PMID- 1600314 TI - Cushing's syndrome due to primary pigmented nodular adrenocortical disease with cardiac myxomas and mucocutaneous lentigines. AB - A young Japanese female demonstrated unusual features of Cushing's syndrome, cardiac myxomas and mucocutaneous lentigines. At the age of 12 years she presented with growth failure and obesity. The dexamethasone suppression test, the metyrapone test and low corticotropin concentrations indicated a primary adrenal disorder. At surgery, the adrenal glands were not enlarged (the right, 4.0 g; the left; 4.5 g) but had numerous small dark brown nodules. The pathological findings showed multiple small black cortical nodules containing large cells with eosinophilic cytoplasm and lipofuscin, and internodular cortical atrophy. These abnormalities were consistent with primary pigmented nodular adrenocortical disease. At age 22 years she complained of fatigue and palpitations associated with mid-chest pain. Four cardiac myxomas, suspected from the echocardiogram, were surgically removed. Because Cushing's syndrome and cardiac myxomas are life-threatening conditions, an awareness of the complex is important. PMID- 1600315 TI - Unanswered questions of the Spanish flu pandemic. PMID- 1600316 TI - [Corneal endothelium. Anatomy, physiology, biomicroscopy, clinical aspects and pathology]. PMID- 1600317 TI - [Surgical anatomy, physiology, biochemistry and questions on the inlay technique]. AB - The chemical identification of collagens and proteoglykans adds to the knowledge of the fine structure of the cornea as seen in histological sections and with the electron microscope. Chemical properties of collagens and proteoglykans help to understand the microscopical appearance of the tissue and some special functions of the cornea, such as transparency, stromal hydration, cohesion, elasticity and shear force resistance. Understanding mechanical properties of the cornea may be valuable for corneal and especially refractive surgery. A review of recent literature on intrastromal implants to be used for optical correction of refractive errors showed, that the resulting problems of corneal nutrition and also those of hydration may be solved by the time. But presumably proteolytic processes around intrastromal implants still prevent longterm tolerance of such implants. PMID- 1600318 TI - [EGF in therapy of corneal diseases. Principles and possible uses]. AB - Numerous recent research results stress the importance of the epidermal growth factor (EGF) for the growth and differentiation of corneal tissues. EGF, a physiological ingredient in the tears, plays a predominant role in the regeneration of corneal epithelium. Furthermore, EGF has been shown to increase the proliferation and differentiation of corneal keratocytes and endothelial cells. Topically applied EGF significantly enhances both the re-epithelialization of denuded areas and the tear strength of stromal cicatrices. These results may lead to interesting pharmacological management procedures for numerous corneal disorders. Thus, the clinical feasibility of EGF therapy is currently the subject of intensive evaluation. A better understanding of its mode of action, both on the molecular and cellular level, and increasing knowledge of the pharmacokinetics, together with the development of suitable application media, may all make EGF an integral part of the next generation of ophthalmic drugs. This survey reviews basic molecular-pharmacological and biochemical findings on EGF and evaluates its possible value for therapeutical use. PMID- 1600319 TI - [The Excimer laser. An instrument for corneal surgery]. AB - Photoablation of the cornea using excimer lasers (193 nm) results in keratectomies with very precise edges and minimal damage to the adjacent tissue. Deep keratectomies for relaxation incisions (astigmatic correction) and for trephination (lamellar or penetrating keratoplasty) are possible, but have not been applied routinely. Superficial keratectomies can induce corneal flattening- a promising approach for correction of myopia. This unique keratorefractive technique, called photorefractive keratectomy (PRK), has been studied worldwide with a follow-up time of up to 2 years. The success rate (+/- 1 D from the refraction aimed at) is approximately 90%, and vision-threatening complications are extremely rare. However, this is true only in corrections of up to -6.0 D. Corrections of more than this result in a significant decrease in the refractive success and a tremendous increase in complications. Therefore, we believe that corrections of more than -6.0 D are clinically not acceptable. Long-term stability is not yet proven, and consequently PRK must be used with strict indications. Superficial scars, corneal dystrophies, and degenerations of the outer cornea can be removed with the excimer laser much more gently than with conventional techniques. PMID- 1600320 TI - [193 nm Excimer laser photoablation of the cornea. Spectrum and transmission behavior of secondary irradiation]. AB - In order to estimate the photomutagenic and phototoxic potential involved we analyzed the spectrum and intensity of secondary radiation induced with a 193 nm excimer laser in photoablation of corneal tissue. The spectrum of secondary radiation was analyzed by an optical multichannel analyzer. A pyroelectrical detector was used to evaluate the energy of the secondary radiation. We found the secondary radiation to be in the range of ultraviolet to infrared. The spectrum has a relatively high quantity (20%) of radiation between 240 and 280 nm. The intensity of the secondary radiation depends on the energy fluence of the primary laser pulse and can reach a quantum yield of up to 10(-3) (at 800 mJ/cm2). At a fluence of 230 mJ/cm2 (193 nm), the secondary radiation in the range of 240-280 nm is approximately 5 microJ/cm2. Radiation below 300 nm was not transmitted through the cornea. Since the high genetic activity of UV radiation in the range from 240-280 nm is well known, evaluation of the potential mutagenicity of 193 nm excimer laser radiation should take into consideration the presence of secondary radiation in this problematic spectral range. However, there is no incidence known for specific UV-induced corneal cancers, which supports the argument that the potential mutgenic risk of clinical excimer laser application can be considered to be low. Because of the full corneal absorption of radiation below 300 nm, there is no risk known for pigmented intraocular structures. PMID- 1600321 TI - [The pathologically changed Descemet membrane. Cultivation of human corneal endothelium on transformed membrane]. AB - Corneal endothelial diseases are connected with structural and biochemical changes of Descemet's membrane (DM). Little is known about the possible effects of these changed basement membranes. In the present study we investigated the influence of changed DM on endothelium. Human corneal endothelial cells were cultured on DM of healthy corneas as well as corneas with Fuchs' endothelial dystrophy or bullous keratopathy, and cell growth and morphology were compared. On healthy DM, cells formed a confluent monolayer within 4 days. Cells cultured on Fuchs' DM showed a similar pattern. The polygonal cell pattern was interrupted merely in the area of the guttae, which were covered by cell processes alone. Culturing cells proved to be difficult on DM from corneas with bullous keratopathy. Even though the cells attached to the DM, they did not spread but became spindle shaped and rarely formed intercellular contacts. Even after 7 days no confluent monolayer was established. These results indicate that some though not all pathological DM changes interfere with cell growth. PMID- 1600322 TI - [The pterygium, Autologous conjunctiva-limbus transplantation as treatment]. AB - Based on a new concept of the limbus as a junctional zone for separating the vascularized conjunctiva from the avascular cornea, this study presents conjunctival/limbal autograft transplantation for 22 cases of pterygium. The pterygia were primary in 17 eyes, cicatricial in 1 and recurrent in 4. In all cases a free transplant of the superotemperal limbus with an adjacent piece of thin conjunctiva was placed in the excision area. Postoperative follow-up ranged from 1 1/2 to 17 months, with a mean of 8.7 months. Only two pterygia recurred. In all other cases ideal anatomic reconstruction was achieved without any side effects. The authors believe that conjunctival/limbal transplantation is an encouraging technique for treating a pterygium surgically. PMID- 1600323 TI - [Precision of lenticular thickness in relation to full stroma corneal thickness. Experimental results with the lamellar microkeratome]. AB - In this study 150 pig corneas and 20 human corneas were dissected with an automatic rotating microkeratome for lamellar grafting. The cornea thickness varied between 0.507 mm and 0.829 with an average 0.66 mm. The aim of this investigation was to show the influence of corneal thickness, the chosen diameter and spacing on the precision of cutting lenticles. We did ten series: the pig corneas were dissected at three different intervals of 0.15, 0.25, 0.35 mm and diameters of 9 and 6mm. The human corneas were cut at intervals of 0.4 mm and 0.25 mm and with diameter of 9 and 7 mm. Although the pig corneas were fresh, the intraocular pressure was too low. It was raised with an injection of physiological salt solution to a predefined level. The rotating speed of the trephine blade, the speed of blade advancement and lubrication fluid were kept constant. Ultrasound pachymetry was performed on the center of the corneas before cutting had on the lenticles afterward. We showed that a thick corneal diameter had a negative influence, i.e., the greater the diameter, the lesser the precision; the same was true for the corneal thickness. On the other hand, the intervals had just the opposite effect: the closer they were, the better the correlation. The human eye results were different in quantity but not in tendency, with less striking effects. The average variation for pig corneas was 22% and for human eyes 8%. The best results were received with a large interval, a small diameter, and a normal corneal thickness in human eyes. PMID- 1600324 TI - [Image quality of various types of intraocular lenses (mono-, bi- and multifocal) in air and water]. AB - Most of the monofocal intraocular lenses tested in air and water showed good-to high resolution in water. There was low resolution in the outer zone of the image in some models. The bifocals tested had a lower resolution efficency with less contrast and change of colors. The diffractive IOL had poor central resolution efficiency with changing colors and double vision. There was a spherical change like a fish-eye. When tested in air there was paracentral double vision in the diffractive IOL with a change of color bands. PMID- 1600325 TI - [The TRUE-VISTA bifocal IOL. Results of the European multicenter study]. AB - In the last few years a number of bifocal IOL has been developed. The True Vista IOL, a three-zone refractive bifocal IOL with central and peripheral distance zones and a pericentral near annulus, was implanted in 367 patients in a prospective European multicenter study between February 1990 and May 1991. Visual acuity, pupil size and astigmatism were determined. At 4-6 months near acuity was measured with reading charts (Nieden Chart) and at 7-11 months with a Snellen chart (Lighthouse Chart). At 4-6 (7-11) months, so far 164 (73) of the patients have been available for follow-up. Best corrected distance acuity was 20/40 or better in 97% (99%), best corrected near acuity was 20/30 or better in 91% (83%), and uncorrected near acuity was 20/30 or better in 64% (59%). Average Snellen near acuity (Lighthouse Chart) was 20/25, slightly lower than the average reading acuity of 20/22 (Nieden Chart) (p = 0.34, Wilcoxontest). Distance and near acuity also decreased with increasing astigmatism and increasing age. Our results demonstrate good visual acuities with the True Vista bifocal IOL. Age and postoperative astigmatism may affect the performance of bifocal IOL. Snellen near acuity is reduced, despite normal reading acuity, but further investigation is required. PMID- 1600326 TI - [Light perception and flicker perimetry. Effect of refractive error, artificial media opacities and pupillary size]. AB - The influence of defocus, artificial media opacities and pupil size on perimetric thresholds in automated light sense and flicker perimetry was investigated in 20 eyes of 20 normal subjects. Thresholds were determined at 13 locations in the central visual field. Blurring the retinal image by a small defocus or by slight artificial media opacities causes a measurable reduction in light-difference sensitivity. Flicker fusion frequency, however, is much more resistant to degradation of the retinal image. Artificial pupil size has a similar effect on both light-difference sensitivity and flicker fusion frequency. The present study shows that perimetric methods using temporal threshold criteria should be more suitable for the detection of neuronal damage in the presence of factors disturbing the quality of the retinal image than methods using static criteria. PMID- 1600327 TI - [Damage to visual capacity]. PMID- 1600329 TI - Autoimmune hemolytic anemia combined with idiopathic thrombocytopenia (Evans syndrome). Sustained remission in a patient following high-dose intravenous gamma globulin therapy. PMID- 1600328 TI - Ventilation and secretion of pulmonary surfactant. AB - Various factors are involved in the regulation of surfactant secretion: chemical agonist; local environmental factors such as mediators, locally produced hormones, and possibly pH; and finally, mechanical stress occurring during lung inflation. Here we suggest a model of regulation which is grouped into three levels: a basal autoregulatory mechanism with local factors being superimposed and a systemic level acting through hormones reaching the lung via the bloodstream. Depending on the situation, the different levels may vary in their importance. For the normal situation, in the absence of stress factors, we suggest the autoregulation of stretch-induced secretion and SP-A inhibition as indicated by in vitro experiments to be the prominent regulatory mechanism for surfactant secretion. From this model, mechanisms can be derived which indicate involvement of the surfactant system in, for example, obstructive lung disease. Support from the literature for this hypothesis is reviewed. Because quantitative measurement of the amount of surfactant-associated phospholipids cannot be done adequately at this time, we suggest testing the relatively risk-free application of exogenous surfactant in a pilot phase based on indications for its involvement and usefulness derived from animal and in vitro experiments. PMID- 1600330 TI - Basal and nutrient-stimulated pancreatic and gastrointestinal hormone concentrations in type-1-diabetic patients after successful combined pancreas and kidney transplantation. AB - The secretion of pancreatic and gastrointestinal hormones in the basal state and after nutrient stimuli (50 g glucose, 50 g protein, or 30 g triglyceride administered on separate occasions) was assessed in ten previously type-1 diabetic patients after successful combined kidney and pancreas transplantation (systemic venous drainage). Fasting values were compared to matched non-diabetic kidney-transplanted patients and related to kidney function (endogenous creatinine clearance) and to the type and dosage of immunosuppressive medication. In the fasting state, only IR insulin concentrations were higher in pancreas kidney-transplanted patients (by 88%; P = 0.001) than in the kidney graft recipients. There were significant inverse correlations of plasma C-peptide, GIP, and gastrin immunoreactivity to endogenous creatinine clearance (kidney function). In response to nutrients, insulin secretion (IR insulin, C-peptide) was significantly stimulated by glucose, and - to a lesser degree - also by protein. Pancreatic glucagon was suppressed by glucose and stimulated by protein ingestion. GIP was raised after glucose and triglyceride more than after protein (P = 0.0003). GLP-1 immunoreactivity was stimulated by all nutrients, with a tendency towards higher responses to protein and fat (P = 0.06). Gastrin was mainly raised by protein. In conclusion, the overall pattern of pancreatic and gastrointestinal hormone release is normal in patients after combined pancreas kidney-transplantation, but there are some peculiarities due to (a) systemic venous drainage of the pancreas graft (elevated fasting IR insulin) and (b) impaired kidney function (negative correlation of fasting plasma values to endogenous creatinine clearance for C-peptide, GIP, and gastrin).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600331 TI - Alterations in bilirubin metabolism during extra- and intrahepatic cholestasis. AB - This study was performed to investigate modifications in the serum bilirubin forms, hepatobiliary enzymes, and some glycoproteic substances in patients during the course of extrahepatic cholestasis (stage A) and following its clinical resolution (stage B). The series consisted of 16 patients: 11 had main bile duct stones; two, benign stenosis of the main bile duct; and three, main bile duct cancer. Cholestasis resolved spontaneously in one case, under endoscopy in two, and following surgery in 13. Five patients with liver cirrhosis and a picture of intrahepatic cholestasis following anesthesia were also investigated. Serum bilirubin forms were measured using van den Bergh's method and the alkaline methanolysis-HPLC procedure; the mono- and di-conjugated forms were considered together in the overall evaluation of the results. The hepatobiliary enzymes (ALP, GGT, and AST) were increased at stage A and significantly decreased at stage B. Similar patterns were observed in total (TB), unconjugated (UB), and conjugated bilirubin (CB) and in the percentage of CB out of TB (% CB). In the majority of patients, % CB at stage B was lower than at stage A, whereas in subjects with a high initial UB value, a different % CB pattern was observed. The direct bilirubin percentage (% DB), on the other hand, had a different pattern, and the variations between stages A and B were not significant. The pathophysiological bilirubin pattern was similar in patients with intrahepatic cholestasis. At stage A, in a number of patients the levels of glycoproteic substances (CA 19-9, TPA and ferritin) were raised, but at stage B they tended to decrease towards the normal range.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600332 TI - Successful treatment of recurrent hepatic Candida infection with fluconazole after chemotherapy for acute leukemia: a case report. AB - Hepatic candidiasis represents an increasingly difficult problem in immunocompromised patients. It has been recognized as a variant of disseminated candidiasis after a period of neutropenia. Establishment of diagnosis is difficult since liver biopsy as well as culture may be negative, in spite of the presence of fungus. Hepatic lesions are generally not detectable by ultrasound examination or computed tomography until the neutrophil count has returned to normal. The aim of this case report is to describe the problems related to the diagnosis and treatment of hepatic candidiasis following chemotherapy for acute leukemia. The report also provides further evidence that fluconazole, a new broad spectrum antifungal drug, can be safely and effectively used for the long-term treatment of deep-seated hepatic candidiasis. PMID- 1600333 TI - Current concepts: converting enzyme inhibitors in coronary artery disease. AB - Studies investigating the antiischemic action of converting enzyme inhibitors (CEIs) in patients with coronary artery disease (CAD) have, after single dosing, provided evidence for mechanisms of action such as coronary vasodilation and reduction of myocardial oxygen-consumption due to pre- and afterload reduction. Measurements of exercise-induced ST-segment depression and exercise duration as criteria for clinical efficacy have revealed contradictory findings. Patient characteristics, which may be important for a satisfactory response to CEI treatment, have yet to be identified. Patients with ischemic left ventricular dysfunction may benefit from CEI therapy. Neurohumoral factors, e.g., plasma renin activity and atrial natriuretic peptide, may also be relevant. The anti ischemic efficacy of CEIs given as monotherapy has not yet been convincingly demonstrated. The protective effect of CEI treatment with regard to ventricular enlargement after myocardial infarction seems to be established; however, data on mortality are still outstanding. PMID- 1600335 TI - The natural course of atrial septal defect in adults--a still unsettled issue. PMID- 1600334 TI - Familial defective apolipoprotein B-100: a common cause of primary hypercholesterolemia. AB - Familial defective apolipoprotein B-100 (FDB) is a recently identified dominantly inherited genetic disorder characterized by a decreased binding of low density lipoprotein (LDL) to the LDL receptor due to defective apo B-100. FDB is caused by a G to A mutation at nucleotide 10,708 in exon 26 of the apo B gene creating a substitution of glutamine for arginine in the codon for amino acid 3500. The arginine (3500)----glutamine mutation has been observed in several populations in North America and Europe with a similar frequency of approximately 1/500 to 1/700. Haplotype analysis has demonstrated that the arginine(3500)----glutamine mutation occurs on the same chromosomal background. The fact that all individuals with FDB are of Caucasian extraction implies that the mutation has its origin in this population. The arginine(3500)----glutamine mutation has a profound impact of varying strength on the plasma LDL cholesterol level, leading to heterogeneous clinical expression comparable to "classic" familial hypercholesterolemia (FH) caused by a defective LDL receptor: tendon xanthoma, premature atherosclerosis and arcus lipoides. The present data suggest that the combination of these clinical features is no longer appropriate for the diagnosis of LDL-receptor defective FH, but may be a common feature of a defective LDL receptor pathway originating either from defective LDL receptors or from malfunctioning ligand apo B-100. PMID- 1600336 TI - Effects of a high-cholesterol diet on arterial wall thickness and vascular reactivity in young rabbits. AB - Cholesterol enrichment of arteries may induce biochemical and structural abnormalities in vascular smooth muscle resulting in increased arterial contractile sensitivity. We studied the effects of a high-cholesterol diet on arterial structural properties and vascular reactivity in young rabbits. In vivo measurements of aortic intimal-plus-medial thickness using high resolution ultrasound imaging were obtained before and after 3 weeks of a high-cholesterol diet in 12 rabbits (group 2) and compared to data from 12 animals a cholesterol free diet fed (group 1). Six rabbits (group 3) were studied before and after a 3 week, high-cholesterol diet and after a subsequent 13-week, cholesterol-free recovery diet. Blood pressure responsiveness to noradrenaline was evaluated before and at the end of each diet period. In groups 2 and 3, high dietary cholesterol caused an increase in intimal-plus-medial thickness from 0.31 mm and 0.33 mm to 0.88 mm and 0.89 mm, respectively (p less than 0.001). Plasma cholesterol concentration rose from 0.9 +/- 0.26 mmol/l to 36.7 +/- 8.56 mmol/l. There was no change in group 1. In group 3, intimal-plus-medial thickness remained increased (1.01 mm) following the cholesterol-free recovery diet despite normal plasma cholesterol. Blood pressure responsiveness to noradrenaline was markedly increased after the high-cholesterol diet (p less than 0.001) in groups 2 and 3 and after the cholesterol-free recovery diet in group 3 (p less than 0.001), and was directly related to intimal-plus-medial thickness (r = 0.84; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600337 TI - Is soluble CD25 antigen (interleukin-2 receptor) a useful parameter for differential diagnosis of thyrotoxicosis? AB - Soluble CD25 antigen was measured in 28 patients with Graves' disease and 20 patients with thyroid autonomy in order to address the question of whether this parameter could be used in the differential diagnosis of thyrotoxicosis. Soluble CD25 was significantly elevated in active Graves' disease (2430 +/- 442 U/ml, mean +/- SEM) compared to patients with thyroid autonomy (1295 +/- 225 U/ml, mean +/- SEM). However, compared to normal controls (mean 605 +/- 49 U/ml), both groups of patients had significantly elevated CD25 plasma levels. Investigations in thyroidectomized thyroid cancer patients on and off T4 suppressive therapy showed no influence of T4 on the CD25 level. Soluble CD25 concentrations did not differ in thyroid cancer patients compared to normal controls. We conclude that soluble CD25 may indicate a stimulation of the immune system with high sensitivity; however, due to the low specificity of elevated CD25 levels, its usefulness for differential diagnosis of thyrotoxicosis is limited. PMID- 1600338 TI - Low incidence of antibody formation due to long-term interferon-alpha 2c treatment of cancer patients. AB - In order to study the long-term immunogenicity of interferon-alpha 2c (Berofor) in cancer patients, serum was collected starting in 1983 from study patients with various proliferative diseases who received interferon-alpha 2c at different doses, according to different schedules, and via different routes. A total of 1992 samples were tested for the presence of anti-interferon-alpha 2c antibodies. Due to long-term interferon-alpha 2c treatment, 346 patients were eligible for induction of neutralizing anti-interferon antibodies over a treatment period of 2 52 months. Most patients were treated for longer than 6 months. Of the 346 patients, three patients (0.87%) exhibited measurable titers of neutralizing antibodies following therapy with interferon-alpha 2c. One hundred and sixty three patients suffered from non-Hodgkin lymphomas, leukemias, and preleukemias. One patient with chronic myeloid leukemia experienced antibody induction under therapy. The other 183 patients had solid tumors. Two of them reacted with antibody production. All titers were very low (1:12, 1:8, and 1:64). Compared with figures reported for other interferon-alpha preparations, the propensity of interferon-alpha 2c to induce neutralizing antibodies seems to be very low. This property might be related to arginines occurring as critical residues in positions 23 and 34 of the interferon-alpha 2c molecule. PMID- 1600339 TI - Erythropoietin in thrombotic thrombocytopenic purpura and acute renal failure. AB - In this study, erythropoietin serum levels were serially determined in eight patients with acute renal failure to get a lead on the etiology of anemia in acute renal failure and to address the relationship between erythropoietin synthesis and renal excretory performance. Erythropoietin serum levels rapidly decreased after onset of acute renal failure to values of 12.8 +/- 10.3 mU/ml compared to 16.8 +/- 9.4 mU/ml in healthy controls. After restoration of renal function, erythropoietin levels climbed slowly in six patients (15.2 +/- 5.3 mU/ml), and in relation to prolonged anemia in these patients, a relative deficiency of erythropoietin could be observed. In one patient with thrombotic thrombocytopenic purpura causing acute renal failure, the decline of erythropoietin secretion was not observed, and in a phase of the disease when plasma exchange therapy was interrupted, markedly increased erythropoietin levels, up to 182 mU/ml, were detected despite the renal failure. Focusing on erythropoietin secretion in thrombotic thrombocytopenic purpura, we followed hormone synthesis in two other patients with the same disease, one of whom had mild renal insufficiency and one had normal renal function. High erythropoietin levels of up to 205 mU/ml were found in these patients, similar to the peak levels found in the patient with complete renal failure. Plasmapheresis treatment reduced erythropoietin production in all three patients with thrombotic thrombocytopenic purpura. In summary, our study indicates that in most cases of acute renal failure, erythropoietin synthesis is compromised and may contribute to the development of anemia in renal failure and aggravate the persistence of anemia after restoration of renal function.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600340 TI - Intraductal shock-wave lithotripsy in complicated common bile duct stones. AB - Intracorporeal shockwave lithotripsy was performed in 36 patients with problematic common bile duct stones. All of the patients had undergone unsuccessful mechanical lithotripsy prior to this procedure. In 29 patients (80.6%), the stones were fragmented under cholangioscopic control and subsequently extracted with a Dormia basket. In seven patients, the procedure failed due to stone impaction or failure to intubate the common bile duct with a nasobiliary tube. No complications were observed. Cholangioscopically guided intracorporeal shockwave lithotripsy is a highly effective and safe procedure for the conservative treatment of complicated common bile duct stones. PMID- 1600341 TI - Idiopathic portal hypertension in a renal transplant patient after long-term azathioprine therapy. AB - We report the case of a patient with renal insufficiency who was admitted for the evaluation of splenomegaly. He had received a kidney allograft 6 1/2 years ago. Treatment with azathioprine and prednisolone for immunosuppression had been discontinued 1 year before admission. The underlying cause of the splenomegaly appeared to be an idiopathic portal hypertension. Until now, this disease has been described in only 13 kidney transplant patients receiving long-term immunosuppressive therapy with azathioprine. For the first time we demonstrate that azathioprine can cause this chronic liver disease even if the drug has been withdrawn some time before. Therefore, the indication for azathioprine must be considered very carefully. PMID- 1600342 TI - Incarcerated bariolith of the cecum eight months after a barium meal. AB - Barioliths consist of inspissated barium mixed with feces. They are a rare complication after barium contrast roentgenography and occur almost exclusively in the large bowel. Mostly asymptomatic or causing only slight symptoms and signs, they may persist for months or years. We report a severe case of cecal bariolith. Clinical symptoms and signs, radiological findings, intraoperative findings, and histology are presented and discussed with reference to the literature. PMID- 1600343 TI - AL amyloidosis mimicking a preferentially autonomic chronic Guillain-Barre syndrome. AB - We report a case history of a patient whose diagnosis of AL amyloidosis remained elusive until postmortem examination. Exhaustive autonomic neuropathy mimicking a chronic Guillain-Barre syndrome dominated the clinical picture. The problems in establishing the definitive diagnosis of AL amyloidosis even in the face of strong clinical evidence are discussed. PMID- 1600344 TI - Patient compliance with drug treatment--new perspectives on an old problem. AB - Compared to other variables being considered in therapeutics, patient compliance has long been given minor attention although it affects every aspect of medical care. Limited methodology of compliance measurement, in particular, has hampered major progress in research, and pre-conceptions have been reiterated. However, there is a recent surge in interest derived from new data revealed by reliable methods, i.g. continuous medication (compliance) monitoring. The visualization of dynamics in drug regimen compliance over time offers unique opportunities, both to scientific drug evaluation and therapeutics in medical practice. New perspectives related to the descriptive and explanatory side of the problem are outlined by giving examples from various therapeutic fields. PMID- 1600346 TI - Long-term experience with extracorporeal low-density lipoprotein cholesterol removal by dextran sulfate cellulose adsorption. AB - Patients with familial hypercholesterolemia have a high incidence of coronary heart disease due to diet- and drug-resistant, elevated low-density lipoprotein cholesterol (LDL-C). Five patients with familial hypercholesterolemia and diet- and drug-resistant LDL-C greater than 230 mg/dl were treated by LDL apheresis using dextran sulfate cellulose adsorption (Liposorber System LA-15, Kaneka). Plasma separation was by 0.5-m2 polysulfone hollow fiber filter. Two columns containing 150 ml of dextran sulfate cellulose alternately adsorbed LDL and were regenerated by 4.1% saline. The five patients received a total of 360 treatments at 7-day intervals. The treated plasma volume per session was 4.1 +/- 0.4 l. Postapheresis values compared with preapheresis were: total cholesterol, 40%; LDL C, 28%; VLDL-C, 65%; HDL-C, 95%; triglycerides, 70%; white blood cells, 116%; platelets, 87%; C3 complement, 79%; fibrinogen, 64%; albumin, 94%. The decrease in HDL-C per treatment was not significant. The safety parameters showed only slight changes. The initial LDL of 436 +/- 172 mg/dl decreased to mean pre apheresis levels of between 150 and 100 mg/dl. The anti-atherogenic HDL increased in three and remained unchanged in two patients. Adverse events like hypotension, angina pectoris, and technical problems occurred in 11 of the 360 treatments. Long-term treatment of patients with diet- and drug-resistant familial hypercholesterolemia by extracorporeal dextran sulfate cellulose adsorption is effective and safe. PMID- 1600345 TI - Endothelial heterogeneity and the acquired immunodeficiency syndrome: a paradigm for the pathogenesis of vascular disorders. AB - Vascular disorders comprise a wide range of diverse disease entities. Correspondingly, vessels, and even more so the endothelial which line them, show a remarkable extent of heterogeneous differentiation, e.g. between the blood vascular and lymphatic systems, along the length of the vascular trees, and in the microvascular beds of various organs. The most important morphologic criterion to discriminate between endothelia is continuity (continuous endothelial cell layer and well-formed basement membrane) versus discontinuity (intra- or intercellular gaps and/or reduced or missing basement membrane). Most blood vascular endothelia are of the continuous type, while most sinusoidal and lymphatic endothelia are discontinuous by these criteria. Antigen expression corroborates these morphologic data in that CD31, CD34, and 1F10 antigen are exclusively expressed in continuous endothelia, while MS-1 antigen is preferentially expressed in non-continuous sinusoidal endothelia. In contrast, no specific marker has as yet been described for lymphatic endothelia. Endothelial heterogeneity substantially contributes to the pathogenesis of vascular disorders. For example, in patients with acquired immunodeficiency syndrome the same infectious agent may cause either bacillary angiomatosis (a lobular capillary proliferation) or peliosis (sinusoidal dilatation, endothelial denudation, and development of blood-filled cysts) depending on whether the affected organs have predominantly continuous endothelia or noncontinuous sinusoidal endothelia. Moreover, in Kaposi's sarcoma, it is still an open question of whether the lesion is derived from blood vascular or lymphatic endothelia (Kaposi's sarcoma cells in situ do not express the von Willebrand factor+, PAL-E+, 1F10+ phenotype of mature, resting blood vascular endothelia). It is also unresolved how endothelia of either type may be differentially induced to dedifferentiate and how they are recruited into the lesion. Clearly, knowledge about endothelial heterogeneity is still too incomplete to identify the actual mechanisms and molecules that govern the pathogenesis of vascular disorders (including still others than those mentioned here such as atherosclerosis, diabetic angiopathy, and rheumatoid arthritis) affecting distinct endothelia. Further efforts in antigenic phenotyping and in cell and molecular biology of heterogeneously differentiated endothelia should be made to improve this state of affairs. PMID- 1600347 TI - Coin lesions in patients returning from countries with a different climate. PMID- 1600348 TI - Cellular origin of aldosteronomas. AB - In the 1950s, after years of suspicion and work by many investigators regarding a potent mineralocorticoid hormone from the adrenal cortex, aldosterone was at last isolated and chemically identified [40, 41]. Soon after, Jerome Conn was the first to report [11] the clinical correlate of excessive secretion of aldosterone from a benign adrenocortical tumor manifested by hypertension and hypokalemia with the increased urinary excretion of aldosterone. This tumor is often called as aldosteronoma, and the disorder produced by it has been called primary aldosteronism by Conn. In the vast majority of patients harboring such tumors, the hypertension is cured by the resection of the tumor [12, 51], although some suggest that the hypertension may recur in a proportion of apparently cured patients [3, 36]. Thus, primary aldosteronism represents one of a few potentially curable forms of hypertension. Since aldosterone is elaborated normally by the zona glomerulosa cells of the adrenal, it has been assumed that all aldosteronomas originate from the cells of the glomerulosa zone. A clonal origin of aldosteronomas has also been suggested [28]. Some earlier and recent developments, however, indicate that functionally there may be more than one type of aldosteronomas and that their cellular origins might be different. PMID- 1600349 TI - Endocrine abnormalities in mitochondrial myopathy with external ophthalmoplegia. AB - Endocrine functions were examined in 21 patients with mitochondrial myopathies presenting with chronic progressive external ophthalmoplegia and other additional neurological and multisystemic symptoms. Ten patients had the features of the Kearns-Sayre syndrome. Deletions of the mitochondrial DNA were found in 4 out of 5 patients examined. Fourteen patients, including 3 with deletions of the mitochondrial DNA, had various and often multiple endocrine abnormalities: 6 patients were of short stature, 3 had irregular menstrual cycles, 3 had undersized testicles, 5 showed an insufficient rise of growth hormone following the administration of growth-hormone-releasing hormone, 4 showed an insufficient rise in FSH after administration of gonadotropin-releasing hormone, 5 had manifest diabetes mellitus, 3 showed an impaired glucose tolerance, and 2 patients had subnormal serum levels of parathormone in combination with hypocalcaemia. One patient additionally had Klinefelter's syndrome with a kariotype 47, XXY and increased levels of FSH and LH, subnormal levels of testosterone and subnormal testicular volume. The occurrence of endocrine defects correlated with the duration of disease. The data demonstrate that endocrine abnormalities are frequently associated with mitochondrial myopathy, indicating that this multisystemic disease also involves various endocrine tissues. PMID- 1600350 TI - Anatomical and functional cardiac abnormalities in type I diabetes. AB - To analyse the anatomy and systolic and diastolic cardiac function in a group of type I diabetics with no other abnormality and to correlate it with the duration of the disease, the presence of complications, the control of the diabetes and the abnormalities in the autonomous nervous system, 125 type I diabetics and 50 age- and sex-matched healthy controls were studied. In 112 diabetics, an echocardiographic image which enabled us to calculate the thickness, cavity dimensions and systolic function rates was obtained. A Doppler echocardiograph was done in all patients to measure 9 parameters of diastolic function. The autonomic nervous system was evaluated by the response to 4 cardiovascular reflexes. Two control groups and 4 study groups were established, based on duration and on the presence and number of microangiopathic complications. The results showed a significant increase in the septal and posterior wall thickness, although without differences between the study groups. There were no differences in the analysis of systolic function. The abnormalities in diastolic function were significant in all the groups, but greater in the groups with microangiopathy. Overall, for groups 1-4, respectively, the incidence of anatomical abnormalities was 9.6%, 17%, 28% and 57% (average 22%); systolic 0%, 0%, 4% and 4.7% (average 2.2%); and diastolic 15%, 21%, 60% and 80% (average 44%). Only 13 diabetics from group 4 presented with cardiac autonomic neuropathy. No correlation between these alterations and the glycaemic control or the duration of the disease was found, although there was a correlation between the presence or absence of complications and the anatomic and diastolic abnormalities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600351 TI - Metabolic alkalosis as driving force for urea synthesis in liver disease: pathogenetic model and therapeutic implications. AB - Despite a marked reduction of the urea cycle capacity, patients with well compensated chronic liver disease excrete near-normal amounts of urea. Compensation of the urea cycle defect apparently occurs through the activation of liver glutaminase, as suggested by an inverse relationship between the in vitro ureagenic capacity and the flux through glutaminase in liver tissue from patients with a normal, fatty, or cirrhotic liver. In these patients, the flux through glutaminase, as determined in vitro, increases in parallel with the plasma bicarbonate level and plasma pH determined in vivo. In view of this and results from previous studies, the following hypothesis is suggested: The decrease of urea cycle enzyme activities in liver cirrhosis produces metabolic alkalosis due to an impaired bicarbonate elimination. Alkalosis in turn activates and stabilizes hepatic glutaminase and accordingly mitochondrial ammonia provision for carbamoylphosphate synthetase. This results in a compensatory stimulation of the urea cycle flux in the cirrhotic patient to near-normal rates, despite the marked reduction of urea cycle enzyme activity. Accordingly, alkalosis is an important driving force for urea synthesis in the cirrhotic patient. With respect to clinical medicine, attention must be paid to acid-base disturbances in the hyperammonemic patient. PMID- 1600352 TI - Hemodynamic effects of amiodarone during acute and chronic treatment in patients with recurrent sustained ventricular tachycardia. AB - In 15 patients with recurrent ventricular tachycardia, the hemodynamic effects of amiodarone were evaluated under oral loading (1000 mg/day for 14-16 days) and during chronic treatment (600 mg/day for a further 10 weeks). In all patients, coronary artery disease was present with a mean ejection fraction of 37%+/- 10%. The cardiac output during the sinus rhythm, as determined by thermodilution, did not change significantly during loading with amiodarone. During ventricular tachycardia, the cardiac output increased from 3.7 +/- 1.3 to 4.5 +/- 1.6 1/min under the influence of amiodarone in 5 patients. Echocardiographic measurements of the left ventricle dimensions did not show a directed change of the enddiastolic and endsystolic diameters and the fraction shortening at the end of the loading period and after 3 months of maintenance therapy. No negative inotropic effect of amiodarone could be demonstrated in patients with recurrent ventricular tachycardia and impaired left ventricular function due to coronary artery disease. PMID- 1600353 TI - Force-frequency relationship and inotropic stimulation in the nonfailing and failing human myocardium: implications for the medical treatment of heart failure. AB - In isolated papillary muscle strips from nonfailing donor hearts (NF) and from the hearts of patients with dilated cardiomyopathy with severe heart failure (NYHA IV), the force-frequency relationship was studied. Experiments were performed under basal conditions and in the presence of 0.01 microM or 0.1 microM isoprenaline and 0.02 microM ouabain. In NF, there was a positive inotropic effect following an increase of the stimulating frequency, whereas in NYHA IV, the force gradually declined under these conditions. Low concentrations (0.01 microM) of isoprenaline prevented the negative inotropic effect in NYHA IV, whereas at 0.1 microM the mechanical function deteriorated in NF and NYHA IV. Ouabain had no effect on the force-frequency relationship compared to basal conditions. It is concluded that a reduction of high frequencies does improve the contractility in the failing myocardium. It is not unreasonable to speculate that this mechanism might be involved in the beneficial effects of drugs which reduce the heart rate, such as beta-adrenoceptor antagonists and cardiac glycosides, in the condition of congestive heart failure in which the sympathetic tone is high. PMID- 1600354 TI - The influence of partial gastrectomy on biochemical parameters of bone metabolism and bone density. AB - Since it has been suggested that gastric resections are followed by changes in bone metabolism, the aim of our study was to determine the biochemical parameters of bone metabolism and radial and lumbar bone density in 15 male ulcus patients treated by partial gastrectomy (Billroth II). Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography was statistically significantly lower (P less than 0.04) in the patient group, whereas the peripheral bone mass of the distal part of the nondominant forearm measured by single-photon absorptiometry showed no statistically significant difference. In addition, a marked increase in alkaline phosphatase (P less than 0.002) and urinary excretion of hydroxyproline (P less than 0.003) was found in gastrectomy group, whereas the 25-hydroxy-vitamin D levels were found to be significantly decreased (P less than 0.04). Osteocalcin, a biochemical marker for osteoblast activity, and the carboxy-terminal propeptide of type I procollagen (PICP), a marker of collagen formation, were slightly but not significantly higher in gastrectomy-treated patients. The serum parathyroid hormone levels were similar in both groups. As none of the patients had any radiologic evidence of osteopenia, the changes in biochemical parameters of bone metabolism and bone mass in patients who had undergone partial gastrectomy could be a marker of latent bone loss. PMID- 1600355 TI - The relationship between serum lipids, nucleation time, and biliary lipids in patients with gallstones. AB - The relationship between biliary lipids, cholesterol saturation index, nucleation time, and serum lipids was studied in a group of 45 gallstone patients (10 male, 35 female; age 50.1 +/- 14.5 years). Bile was obtained by direct fine-needle puncture of the gallbladder under local anesthesia and sonographic monitoring. No significant correlation between the serum lipids and either the cholesterol saturation index or total biliary cholesterol levels was observed. We found a positive correlation between the nucleation time and serum triglycerides content (r = 0.45, p = 0.0018) and a negative correlation between nucleation time and biliary cholesterol level (r = -0.38, p = 0.009). The fatty acids derived from the triglycerides are primarily resynthesized to phospholipids in the liver. When the supply of free fatty acids exhausts the metabolic capacity of the liver as, for example, in fat-rich diets, triglycerides accumulate in the liver cells and may possibly by excreted in the bile. Free fatty acids stimulate mucin hypersecretion in the gallbladder. This mucosal hypersecretion has been assigned a significant role in the formation of gallbladder stones. We also found a positive correlation between the total biliary bile acids and serum high density lipoprotein (HDL)-cholesterol in patients with a rapid nucleation time (r = 0.50, p = 0.0128). This supports the findings of other researchers, which suggests that HDL-cholesterol is devoted primarily to bile acid synthesis. In patients with a short nucleation time, the cholesterol saturation index, total lipid concentration, biliary cholesterol, mean age, and biliary bile acids were statistically different in comparison with patients with a prolonged nucleation time. PMID- 1600356 TI - Are transient pulmonary solitary nodules a common event in human dirofilariosis? AB - Infection by Dirofilaria immitis is a rare cause of solitary pulmonary nodule. We describe the second case of transitory pulmonary nodule found by us in the course of a case-finding study, the third one reported in the literature. The detection of cases of transient pulmonary dirofilariotic nodules suggests that human infection is more prevalent than usually thought, and that this kind of manifestation is frequent in human dirofilariosis. Greater awareness is warranted in endemic areas. PMID- 1600357 TI - Spontaneous gas-forming bacterial myonecrosis caused by group B streptococci and peptostreptococci. AB - We present the case of a patient who spontaneously developed a severe gas-forming infection involving the voluntary muscles of both thighs. The organisms responsible were group B beta-haemolytic streptococci together with peptostreptococci. Following surgical and medical treatment, the patient fully recovered. No predisposing factors, in particular no disease causing immunocompromise, could be identified. PMID- 1600358 TI - Morphology and density features of eosinophil leukocytes in eosinophilic pneumonia. A case report. AB - We compared the morphological characteristics and density properties of eosinophil leukocytes obtained from the blood and bronchoalveolar lavage fluid of a 29-year-old patient with chronic eosinophil pneumonia during exacerbation. The lavage eosinophils were significantly increased in size when compared with blood cells (surface area: 208 +/- 12 microns 2 versus 161 +/- 13 microns 2). Moreover, eosinophils contained slightly more granules (23.4 versus 20.7 per cell surface area), but no difference was found when the number was corrected for cell size. Electron microscopy revealed a loss of granule contents in eosinophils from both blood and bronchoalveolar lavage. Finally, 61% of the lavage eosinophils were hypodense (with a density less than 1.085 g/ml), whereas 96.3% of the blood cells were normodense. In conclusion, our data demonstrate that in chronic eosinophil pneumonia, eosinophils obtained from bronchoalveolar lavage and blood show differences in both their morphology and density, suggesting that eosinophils during migration into the lung may become activated. PMID- 1600359 TI - Conversion of atrial fibrillation to sinus rhythm: a possible side effect of transesophageal echocardiography. AB - Transesophageal echocardiography (TEE) is accepted as the procedure of choice for the diagnosis of intracardiac sources of systemic embolism. A case report is presented on a 74-year-old patient with atrial fibrillation referred for TEE evaluation after an acute embolic event. During TEE, atrial fibrillation converted to sinus rhythm. Although TEE is a very safe method, which is performed in increasing numbers of patients, this is the first reported case of conversion of atrial fibrillation to sinus rhythm during the procedure. We suggest that no restriction should be imposed on the use of TEE in patients with atrial fibrillation, as the small risk associated with conversion of atrial fibrillation is outweighed by the potential diagnostic benefits. PMID- 1600360 TI - Selegiline--an overview of its role in the treatment of Parkinson's disease. AB - Selegiline (10 mg per day) selectively inhibits monoamine oxidase type B and thus thwarts the metabolism of dopamine by this enzyme. Selegiline has been used in the therapy of Parkinson's disease since 1986. It enhances the efficacy of levodopa, allows a reduction of the levodopa dose, and improves fluctuations in disability. It also interacts with mechanisms suspected of playing a role in the progression of the disease. Animal studies have shown that selegiline prevents the development of a Parkinson-like syndrome induced by the neurotoxin MPTP. It decreases oxidative stress resulting from the metabolism of dopamine via MAO-B. Clinical studies have shown that selegiline is effective in the therapy of untreated de novo patients: the progression of symptoms demanding the introduction of levodopa into the therapy was delayed, and the risk of needing levodopa treatment within one year was reduced by 57% with selegiline. The mode of action of this drug in the treatment of early Parkinson's disease is still under discussion. There is strong evidence that selegiline may slow the progression of the disease, but a direct symptomatic effect cannot be excluded. PMID- 1600361 TI - Color-coded duplex sonography in the evaluation of vertebral arteries. AB - The vertebral arteries of 100 healthy subjects were studied with color-coded duplex sonography. All subjects experienced no clinical symptoms attributable to the vertebrobasilar system. Diastolic and systolic flow velocities could be measured in color-coded duplex sonography in 94% of the right and 92% of the left vertebral arteries. The anechogenic band between the transverse processes of the cervical spine which helps to identify the vertebral artery could not be discerned reliably in 18% of the subjects. In these cases the colored blood flow signals were used as a guide line to place the doppler sample volume exactly within the arterial lumen. Thus color coded duplex sonography is a useful tool for a rapid and definitely identification of vertebral artery and for pulsed Doppler flow measurements with velocity spectrum. For measurements in diameter of hypoplastic and normal vertebral arteries gray scale methodic is a more accurate assessment, as some artifacts of color-coded duplex sonography exist. PMID- 1600362 TI - [Distribution of the incidence of sonographically detected focal liver changes in patients with colorectal cancer]. AB - Aim of the following study was to investigate how often liver metastases are detected in oncologic patients as compared to other focal liver lesions. Preoperative sonographic examinations of 209 patients with proven colonic or rectal cancer were studied. In 19 liver metastases were detected, which in only one patient were homogeneous echogenic. Liver cysts were found in 17, hemangiomas in 15 patients, all of whom where solitary lesions and between 6 and 25 mm in diameter. Focal fatty infiltration was diagnosed in 14 patients. In conclusion, a sonographically detected liver lesion, which is homogeneous echogenic and less than 20 mm in size, is most likely to be a hemangioma and should be further investigated, if therapeutically relevant. PMID- 1600363 TI - Cholescintigraphic demonstration of transient and functional common bile duct obstruction in a patient with acute pancreatitis. AB - Cholescintigraphy has proven useful in diagnosis of acute and chronic cholecystitis and evaluation of common bile duct obstruction. Common bile duct obstruction may be due to mechanical obstruction such as impact stone in the common duct or functional obstruction due to sepsis with intra-hepatic cholestasis or acute viral hepatitis. We present a cholescintigram of a patient with acute pancreatitis showing complete common bile duct obstruction. PMID- 1600364 TI - [Imaging in isolated pulmonary immunocytoma]. AB - A extranodal pulmonary immunocytoma that originated from the lung is reported. It was hidden behind the picture of a mid-lobe syndrome at repeated imaging controls over a 1.5-year period. In the further course a local progression occurred displayed by roentgenography and computer tomography including calcifications within the pulmonary tumor. A newly developing monoclonal gammopathy was detected by immunoelectrophoresis at the same time. Bronchopulmonary symptoms due to the tumor did not exist. After local resection of the lymphoma monoclonal gammopathy disappeared. However, a recurrence of monoclonal gammopathy developed after eight months. PMID- 1600365 TI - [Sonography in therapy-oriented diagnosis and after-care of primary bone and soft tissue tumors]. AB - Based on the results of 150 patients with primary tumors or the suspicion of malignant lesions of the locomotor system the perspectives and limits of the sonographic diagnosis under the therapeutic aspects of interdisciplinary oncologic cooperation is demonstrated. As the ideal adjunct to conventional roentgenograms, ultrasound is the first-line imaging procedure in the fields of primary diagnosis, follow-up, post-therapeutic care as well as tumor exclusion for methodic, patient-related and economic/logistic reasons. Its consequent application will markedly reduce the number of more invasive and expensive methods. PMID- 1600366 TI - [Ultrasound diagnosis of isolated vagus neurofibroma in Recklinghausen disease]. AB - We report on an isolated cervical vagus nerve neurofibroma in a patient with neurofibromatosis Recklinghausen. B-scanechography showed a well limited tumor without infiltration of adjacent structures and with cranial and caudal dendrites. The inner structure of the neurofibroma was characterized by a homogenous picture of low ultrasound reflection. Although ultrasound allows an exact description of the tumor's topography, it is impossible to give a histological interpretation by the sonomorphology. PMID- 1600367 TI - High performance liquid chromatography of spermidine and spermine using a postcolumn reactor of immobilized polyamine oxidase (Aspergillus terreus) followed by electrochemical detection. AB - A highly sensitive and selective method for the determination of spermidine and spermine has been developed. A polyamine oxidase (Aspergillus terreus) immobilized column was used as a postcolumn reactor. The detection limit was 0.2 pmol/injection for both spermidine and spermine with a linear range of three orders of magnitude. PMID- 1600368 TI - Quantitation of the enantiomers of rimantadine and its hydroxylated metabolites in human plasma by gas chromatography/mass spectrometry. AB - A gas chromatographic/mass spectrometric procedure has been developed for the quantitation in human plasma of the enantiomers of rimantadine and its three hydroxylated metabolites. The assay utilized derivatization of all analytes with the optically active reagent S-alpha-methyl-alpha methoxy(pentafluorophenyl)acetic acid, selective ion monitoring, methane negative ion chemical ionization mass spectrometry and stable isotope dilution techniques. This method has been used to measure plasma concentrations of the enantiomers of rimantadine, m-hydroxyrimantadine and p-hydroxyrimantadine (equatorial and axial epimers) in the ranges 2.5-250, 2.5-50, 1.25-62.5 and 1.25-62.5 ng/mL, respectively, in six subjects given a single 200 mg dose of racemic rimantadine. Although there are no significant differences in the concentration-time profiles of R- and S-rimantadine, large stereospecific differences in the disposition of their metabolites are observed. PMID- 1600369 TI - A sensitive and specific high performance liquid chromatographic assay for imidazole dipeptides and 3-methylhistidine in human muscle biopsies, serum and urine. AB - A sensitive and specific high performance liquid chromatographic method is described for measuring imidazole dipeptides and 3-methylhistidine in human muscle biopsies, serum and urine. Muscle extract, serum or urine was reacted with o-phthaldialdehyde and the derivatives were separated by reversed phase chromatography with column switching and fluorescence detection. PMID- 1600370 TI - Determination of nifedipine in plasma by a rapid capillary gas chromatographic method. AB - A rapid, specific and reliable gas chromatographic assay procedure for Nifedipine in plasma has been developed. With a single-step solvent extraction, and electron capture detection, the method is sensitive to 0.5 ng/mL of plasma and the standard curve is linear from 0.5 to 500 ng/mL. Samples are protected from light to prevent formation of photodecomposition products. The method has been used to monitor drug concentrations in patients receiving therapeutic doses. PMID- 1600371 TI - Quantitative determination of valproic acid and 14 metabolites in serum and urine by gas chromatography/mass spectrometry. AB - A method for the determination of the antiepileptic drug valproic acid and 14 of its metabolites in serum and urine by gas chromatography/mass spectrometry with selected ion monitoring of the trimethylsilylated derivatives has been developed. Sample preparation, including hydrolysis of VPA-conjugates and removal of urea in urine is carried out at pH 5.0 and is rapid and simple. The samples are extracted with ethyl acetate and the concentrated extracts are trimethylsilylated. Analysis with adequate separation of metabolites is achieved with a DB 1701 fused silica (Megabore) capillary column. The method exhibits high recovery and reproducibility and is sufficiently sensitive and selective for analysis of small sample volumes. Application of the method for screening patient serum and urine samples for unusual metabolite patterns, with possible predictive value for early detection of liver injury, is presented. PMID- 1600372 TI - Reversed phase high performance liquid chromatographic separation of hydroxy steroidal unsaturated esters and their hemisuccinates. AB - The high performance liquid chromatographic (HPLC) separation and identification of 12 isomeric and/or highly chemically related steroids with an unsaturated ester moiety at position 17 beta has been achieved. The main stereochemical features of the steroid skeleton cover 3 alpha/beta, 5 alpha/beta or delta, and 20 E/Z, bearing the alcohol or hemisuccinate group at the 3 position. The isocratic reversed phase C18 HPLC separation employed ethanol, methanol and its mixtures with water or 0.01 M phosphoric acid as the mobile phase. The best separation of the respective alcohols from their hemisuccinates has been achieved with 20% of aqueous phase content. The best separation among isomeric or related steroids has been achieved with methanol:water 8:2 and 85:15 and similar systems containing phosphoric acid. PMID- 1600373 TI - Favourable biospecific reactivity of blood group B antigenic trisaccharide chemically attached to poly-N-(2-hydroxyethyl)acrylamide-coated porous glass. AB - Blood group B antigenic trisaccharide-beta-aminopropyl glycoside (B-TSAP) covalently attached to poly-N-(2-hydroxyethyl)acrylamide-coated porous glass interacts with anti-B monoclonal antibodies faster than the ligand coupled to CNBr-activated Sepharose 4B and Affi-Gel 10. Rates of hydrophobic adsorption of antibodies on the butyl derivatives of the same supports were measured to evaluate the diffusion input to overall kinetics. The lowest average affinity adsorption time [t1(aff) = 250 s] observed for polymer-coated glass probably arises because of the flexibility of the extended segments of chemisorbed N substituted polyacrylamide acting as effective spacer arms. PMID- 1600374 TI - Preparation of glycine-conjugated bile acids and their gas/liquid chromatographic analysis on an aluminum-clad flexible fused silica capillary column. AB - This paper describes a method for the direct gas/liquid chromatographic (GC) analysis of 46 glycine-conjugated bile acids, which differ from one another in the number, position and configuration of the hydroxyl groups at positions C-2, C 3, C-4, C-6, C-7 and/or C-12. Free bile acids were converted quantitatively on a micro scale to ethyl ester-trimethylsilyl (Et-TMS) and methyl ester dimethylethylsilyl (Me-DMES) ether derivatives of the corresponding glycine conjugates. The Et-TMS and Me-DMES ethers of the glycine conjugates were chromatographed on an aluminum-clad flexible fused silica capillary column coated with a thin film (0.1 micron) of chemically bonded and cross-linked methylpolysiloxane. Relative retention time (RRT) and methylene unit (MU) values were determined for the 46 compounds and their GC behaviour was discussed. The derivatization procedure and the retention data would be useful for the direct GC identification of unknown glycine-conjugated bile acid mixtures extracted from biological samples. PMID- 1600375 TI - Enhanced selectivity of the isolation of basic drugs from body fluids by means of extraction minicolumns and sophisticated elution schemes. AB - The paper presents results and experience obtained in the isolation of a number of basic polar/non-polar solutes (drugs, their metabolites and structural derivatives) from biological samples by using the separation minicolumns Separcol SI and Separcol SI C18 L/T. The aim was to provide insight into some simple procedures yielding optimal selectivity/specificity of the isolation of the studied solutes either by proper selection of the sorbent or by applying sophisticated elution schemes which use to advantage different properties of the eluents/solvents. PMID- 1600376 TI - Determination of 10 alpha-methoxy-9,10-dihydrolysergol, a nicergoline metabolite, in human urine by high performance liquid chromatography. AB - A specific method for the determination of 10 alpha-methoxy-9,10-dihydrolysergol, a nicergoline metabolite (metabolite 2), in urine is described. Metabolite 2 was well separated from the urine components on a reversed phase column, Hypersil ODS 5 microns, using an acetonitrile:pH 3.5 phosphate buffer (40:60, v/v) as the mobile phase at a flow rate of 1 mL/min. UV detection was set up at 220 nm. After addition of a known amount of lysergamide as the internal standard, the compounds were extracted from alkalysed urine on a pre-packed glass column (Extrelut 1) with dichloromethane. With 0.5 mL urine, concentrations down to 0.56 mumol/L could be determined. PMID- 1600378 TI - Vaccines. New approaches to immunological problems. PMID- 1600377 TI - Haemophilus b conjugate vaccines. PMID- 1600379 TI - Influenza vaccines. PMID- 1600380 TI - Approaches to immunization against respiratory syncytial virus. PMID- 1600381 TI - Hepatitis B vaccines: blueprints for vaccines of the future. PMID- 1600382 TI - Recent advances in the development of pertussis vaccines. PMID- 1600383 TI - Human immunodeficiency virus. AB - A successful AIDS vaccine must elicit an immune state that will prevent the establishment of an HIV-1 persistent infection. This is a unique and difficult goal for a vaccine. Most vaccines elicit or prime for immune responses that prevent or attenuate the expression of clinical disease following infection with the pathogen. However, current evidence suggest that, following persistent infection with HIV-1, antiviral immune responses do not prevent the long-term progression to disease. Hence, it seems that the development of the persistent infection must be prevented. The ability of the immune response to accomplish this goal depends upon the efficiency with which the virus establishes persistence in the host. This is unknown for HIV-1. As a result, early efforts at vaccine development have focused on humoral immune responses directed against the virus particle in the attempt to prevent any infection of the host's cells. Studies with chimpanzees, as a model for HIV-1 infection, suggest that virus neutralizing antibodies directed against the third hypervariable (V3) domain of the viral gp120 envelope glycoprotein may be particularly effective in preventing this infection. Studies also are in progress, both in chimpanzees and humans, to define the immunogenicity and effectiveness of various immunogens derived from the viral envelope and core structural proteins. Efforts that have concentrated on the gp120 V3 domain (or PND) have defined the extent of this region's variability and have established elements of generally conserved structure and sequence. The construction of these elements into practical and effective immunogens is an important goal. Finally, it is essential that basic studies be performed to determine if humoral or cellular immune responses directed against virus-infected cells would aid in preventing the establishment of an HIV-1 persistent infection. Such immune responses, if effective and in conjunction with specific virus-neutralizing antibody responses, would enhance the probability that an effective HIV-1 vaccine could be developed. PMID- 1600384 TI - Vaccinia virus vectors. PMID- 1600385 TI - Active immunization strategies using anti-idiotypic antibodies. PMID- 1600386 TI - Passive immunoprophylaxis with human monoclonal antibodies. PMID- 1600387 TI - Immunological adjuvants and their mode of action. PMID- 1600388 TI - Synthetic peptides as vaccines. AB - The economics of vaccines has been a major limitation in the commercial research and development of new approaches. This coupled with the natural scientific desire to simplify and define the composition of effective vaccines argues that the future of vaccines lies in novel approaches that will discover effective and less expensive components. Peptides, whether they are chemically synthesized or produced in bacteria, are an attractive possibility. To substitute linear peptides for complex mixtures of proteins would be a major technical advance and would stimulate tremendous commercial interest. However, at the present time I view this approach still unlikely to be of major practical importance. I conclude this because of the complexity of immunological responses to microorganisms. Even though, in some instances, a cytotoxic T-cell response or even the majority of the antibody response to a pathogen can be defined by a short linear peptide, most people believe that multiple effector functions of the immune system should be stimulated in optimal vaccines. For a small cocktail of peptides to reproduce the diversity of responses elicited by a virus, parasite, or bacterium is unlikely. However, I fully realize that remarkable progress has occurred towards understanding the structural requirements necessary to stimulate cellular and humoral immune responses, and peptides have been integral in the development of this field. Also, the success of several research groups in developing effective antiviral vaccines using short linear peptides argues that I might be painting too dark of a picture. As someone who has used this strategy to explore peptide MHC and peptide-antibody interactions, I am a strong scientific supporter of the approach. In this forum I am purposely cautious in my optimism. As the details of the complex molecular and cellular interactions that control the immune system are elucidated, both the number of strategies and the possible applications of modulating the immune response will increase as well. In addition to protective immunity to pathogens, cancer therapy could be revolutionized if tumor-specific cytotoxic T-cells could be generated routinely. Novel therapeutic approaches to allergy, autoimmunity, and transplantation can be envisioned if the T-lymphocytes responsible for these syndromes could be modulated without total immune suppression. Consequently, I am confident that the experiments described in this chapter will be central to developing exciting new therapeutic and prophylactic compounds, but I am not sure that they will resemble naturally occurring peptides. The one aspect I am confident of is that the capacity of the immune response to protect the organism will continually surprise us. PMID- 1600389 TI - Cholera vaccines. AB - The currently licensed parenteral cholera vaccine has not been a useful public health tool in the control of cholera. Building on the knowledge that primary infection offers significant protection against reinfection and that mucosal immunity mediates this protection, several oral cholera vaccines have been developed. These vaccine candidates or future candidates derived using the techniques of molecular biology will no doubt contribute to the control of cholera. PMID- 1600390 TI - Malaria vaccines. PMID- 1600391 TI - Helminth vaccines. PMID- 1600392 TI - Results of the DGTI workshop on the evaluation of the reactivity of monoclonal anti-D. AB - All D+ samples were detected by all monoclonal antibodies without problems. Very few of the 3000 D- samples showed a +/- to ++ reaction with some of the IgG type mabs using the Coombs technique. It is still open whether these are specific reactions with weak positive samples, which were negative with polyclonal sera. IgM type mabs detected up to 100% of the Du samples dependent on the Rh-phenotype and the technique used (CCDuee greater than CcDuee greater than ccDuEe). Most of the CCDuee samples reacted very strong and should no longer be regarded as Du. PMID- 1600393 TI - Safety tests of the intravenous tolerance of immunoglobulins. Multicenter study of the section 'Blood Plasma Constituents' of the German Association of Transfusion Medicine and Immunohematology (DGTI). AB - The Working Group 'Blood Plasma Constituents' of the DGTI has carried out four multicenter trials with human immunoglobulins for intravenous application (IVIG). The ACA method elaborated here has led to relatively consistent ACA results for commercially available IVIG preparations in the participating laboratories. On their own, the in vitro tolerance tests of the IVIGs are not sufficient for safety testing, since there is no clear correlation between the ACA values and the tolerance in a rat model in which changes of blood pressure, pulse rate, ECG and respiratory resistance after administration of IVIGs are determined. The role of polymer constituents in tolerance reactions is to be regarded as substantiated, whereas the tolerance of the dimer fractions of beta-propiolactone treated IVIGs does not differ appreciably from that of their monomer constituents. Determination of the IgG subclass composition requires standardization. The collation of the antibody specificities to the subclasses must be clarified before making inferences with regard to the clinical significance of the subclass composition of the preparations. PMID- 1600394 TI - Age-dependent regeneration of plasma proteins after donor plasmapheresis. AB - To analyze age-dependent effects of a plasma donation on the regeneration of plasma proteins two groups of first time plasma donors were selected (less than 25 years, greater than 50 years). By measurements of hematological and biochemical parameter, immunoglobulins, procoagulators and inhibitors of coagulation before and after a plasma donation the kinetic of regeneration until three weeks was followed up. It can be concluded that a single plasma donation affects the generation in younger and older donors in a different way. Procoagulators and inhibitors show the same behavior, except the donation related elevation of fibrinogen in young donors. Especially the retarded regeneration of cholinesterase and immunoglobulins in the male young group should be taken into consideration for frequent plasma donations and autologous preoperative plasma donations. PMID- 1600395 TI - Biotechnology in transfusion medicine. AB - This paper summarizes in an overview the new possibilities based on biotechnology like monoclonal antibodies and genetic engineering. Examples are given where these new techniques are already used in transfusion work. In addition some perspectives for the future in relation to these techniques are given. PMID- 1600396 TI - [Apolipoprotein E mobility between plasma lipoproteins in intravenous administration of fat emulsions (MCT, LCT)]. AB - Apolipoprotein (apo) E plays a key role in chylomicron metabolism as a ligand for their uptake via the apo B/E- and apo E receptor into the liver. Apo E is not primarily synthesized with chylomicrons but is postprandially transferred to chylomicrons during lipolysis in plasma from high density lipoproteins (HDL). As triglyceride-/phospholipid emulsions given intravenously acquire apolipoproteins in plasma, we set out to investigate a possible transfer of apo E to these artificial lipoproteins and its role during their further metabolism. To this end healthy normolipemic volunteers and carriers of the frequent apo E3/3 phenotype were infused lipid emulsions. The lipoprotein-distribution of apo E during MCT and LCT infusions was monitored over four hours. Infusion of MCT and LCT resulted in a substantial transfer of apo E from HDL to triglyceride rich lipoproteins. During MCT infusion the transfer of apo E seemed to occur more rapidly than during LCT infusion. This could be one of the reasons for the faster metabolism of MCT over LCT. Plasma levels of apo E also decreased significantly during infusion of triglyceride/phospholipid emulsions in accordance with the role of apo E as a ligand for the uptake of the artificial particles into the liver. PMID- 1600397 TI - Erythrocyte apheresis as a method for autologous blood transfusion--a case study in a patient with Vel-antibodies. AB - A 60-year old man was suffering from angina and a percutaneous transluminal coronary angioplasty (PTCA) had to be done. In the preoperative screening procedure antibodies anti-Vel were identified. The patients blood group is 0, rr. The prevalence of the blood group 0, rr, Vel(-) is 1:60,000. Compatible blood groups were not found in the patients family. The only alternative method to give this patient his necessary units of blood was an autologous transfusion procedure, however, because of the patients clinical condition it was necessary to use an erythrocyte apheresis procedure without changing his blood volume. We performed erythrocyte apheresis, using the Fenwal CS-3000. 920 ml blood was collected, Ht 0.67 l/l, enough for three units packed cells compared with random donor blood. The erythrocyte apheresis procedure was performed without any problem. The PTCA was done without complications and transfusions. The units of blood are stored in liquid nitrogen in the central laboratory of blood transfusion, Amsterdam. PMID- 1600398 TI - Human monoclonal antibodies for the differentiation of Rh-D categories. AB - With the introduction of human monoclonal antibodies against antigens of the Rh system it was possible to solve a series of problems, as, for instance, the permanent availability of reagents. Another problem, the classification of D categories with a panel of specific monoclonal antibodies, also might be solved by the production of such antibodies. Especially the classification of Cat. VI cells is of great importance. We present a panel of five human monoclonal antibodies useful for the definition of Rh-D categories. The antibodies are designated as BS221, BS227, BS228, BS230 and BS231. By positive or negative reactions with expected category cells it is possible to determine the corresponding category. All Cat. VI-cells of a defined panel could be identified. Of particular interest is the antibody BS221 due to its reactivity with Cat. VI cells. The fact, however, that BS221 is missing the detection of some Cat. VI cells indicates a further subdivision of Cat. VI. PMID- 1600399 TI - Research and theory related to female reproduction: implications for clinical psychology. AB - Reproduction has been proposed as a cause of debilitation and psychological disturbance for centuries, recently reified through the three reproductive syndromes, the premenstrual syndrome, postnatal depression and the menopausal syndrome. The evidence for the existence of these syndromes is critically reviewed, and the different aetiological theories examined, with particular reference to biological and psychological theories. It is argued that whilst bio medical therapies presently dominate the literature, their efficacy is questionable owing to the lack of clear evidence for a hormonal substrate underlying symptomatology. Psychological interventions are reviewed, and multifactorial or individualized interventions recommended for adoption by clinical psychologists. The role of preventative work, through education, information provision and development of self-help strategies, is discussed. It is concluded that whilst menstruation, childbirth and the menopause do not inevitably have a deleterious effect on women, and the validity of the reproductive syndromes may be questioned, reproduction does act as a salient source of attribution and is a possible contributory factor to distress. Reproduction thus needs to be considered by clinical psychologists, but not privileged above other factors which may contribute to difficulties which individual women may experience. PMID- 1600400 TI - Applications of current cognitive theories of the emotions to the conceptualization of emotional disorders. AB - After a period of neglect the psychological study of emotions is making good progress; work from the perspective of cognitive psychology is currently predominant. Key conceptual and theoretical topics from the psychology of the emotions are reviewed and their clinical implications considered. Particular attention is given to (i) the value of formulating emotional disorder within the framework of a basic theory of emotion that emphasizes its functional value, (ii) analysing the extent to which emotional reactions are 'appropriate' in the sense of having perceptual warrant, (iii) distinguishing between thoughts/images and interpretations of the world in formulating the cognitive aspects of emotional reactions, and (iv) the application of appraisal theory, particularly to complex emotions. PMID- 1600401 TI - Stress in clinical psychology trainees. AB - Levels and sources of stress, as well as coping strategies, were assessed in 287 clinical psychology trainees by means of a postal survey. The estimated prevalence of psychological distress, as measured by the General Health Questionnaire, was 59 per cent, which is higher than that for other reported groups. Factor analysis of self-report stress survey yielded six underlying factors; course structure and organization accounted for the greatest variance in stress ratings. A moderate and significant correlation was obtained between the stress survey and the GHQ. Three-quarters of the trainees reported that they were moderately or very stressed as a result of clinical training. There were no differences between length or type of course, although trainees in their second or third year report more stress than those in the first year. Female trainees had higher GHQ scores than men. The most frequently reported coping strategy was 'talking to trainees'. Scores on the Health and Daily Living Schedule indicated no differences in coping methods between length or type of course. Women reported more use of cognitive and behavioural coping methods, but not more avoidance coping methods. Trainees reported that more support by course organizers and supervisors would make training less stressful. PMID- 1600402 TI - Perfectionism and suicide potential. AB - The present study employed a multidimensional approach to examine the association between perfectionism and suicide threat. The present study also examined whether perfectionism variables predicted variance in suicide threat and suicide intention that is not accounted for by other well-known predictors (i.e. depression and hopelessness). A sample of 87 psychiatric patients completed the Multidimensional Perfectionism Scale, the MMPI Threat Suicide Scale and the Beck Depression Inventory. The Multidimensional Perfectionism Scale assesses self oriented perfectionism, other-oriented perfectionism, and socially prescribed perfectionism. The analyses revealed that socially prescribed perfectionism was the only perfectionism dimension correlated significantly with suicide threat and intent. Moreover, hierarchical regression analyses showed that socially prescribed perfectionism predicted variance in suicide scores that was not accounted for by depression or hopelessness. Overall, the findings suggest that suicide potential is associated with a dispositional tendency to perceive that other people are unrealistic in their expectations for the self. The results are discussed in terms of their implications for intervention. PMID- 1600403 TI - Short-forms of the UK WAIS-R: regression equations and their predictive validity in a general population sample. AB - A sample of 200 healthy subjects, representative of the adult UK population in terms of age, sex and social class distribution, were administered a full-length WAIS-R (UK). Regression equations were built to predict full-length IQ from a series of short-forms. The short-forms ranged from a two-subtest version proposed by Silverstein (1982) to a seven-subtest version proposed by Warrington, James & Maciejewski (1986). Regression equations, their standard errors of estimate and confidence intervals are presented as well as IQ conversion tables. The short forms are evaluated in terms of their validity in predicting full-length IQ and in terms of their clinical utility. The advantages of regression-based estimates of full-length IQ over those derived from conventional prorating are discussed. PMID- 1600404 TI - Eating attitudes in survivors of unwanted sexual experiences. AB - To investigate an hypothesized link between unwanted sexual experiences in childhood and later problems with eating, 21 survivors of sexual abuse completed three questionnaires: the Eating Attitudes Test, the Sexual Events Questionnaire, and the General Health Questionnaire. These women scored high on the EAT, and scores were higher for women who reported more sexual experiences. A similar relation was found between number of sexual experiences and depression, and anxiety and insomnia, but not with somatic symptoms. The implications of these findings for intervention in sexual abuse and eating disorder cases are discussed. PMID- 1600405 TI - Symptom-validity testing of feigned sensory or memory deficits: a further elaboration for subjects who understand the rationale. AB - Symptom-validity testing has been used to detect feigning in patients claiming sensory and memory deficits. Such patients typically give significantly fewer correct responses on forced-choice testing than would be expected by chance. Some subjects have been able to understand the rationale and respond at the chance level. Some have evaded detection by elaborations of the technique which seek evidence of non-randomness in the sequence of correct and incorrect responses. This paper reports the stratagem used by one such subject and a further elaboration of the technique by which it was detected. PMID- 1600406 TI - Psychotic patients' attributions for mental illness. AB - The study examined the attributions concerning mental illness of young psychotic out-patients participating in a rehabilitation programme. The sample consisted of 50 men and 33 women (mean age 26 yrs) diagnosed by their treating psychiatrist as psychotic, with main symptoms: hallucinations (59 per cent), depression (12 per cent), non-specific (29 per cent). Subjects replied to a personally administered questionnaire, designed to obtain ratings of importance for several causes of mental illness, and a measure of how optimistic they felt about their future psychological health. Factor analysis of the subjects' ratings revealed three factors: 'Family - Relationships', 'Personal Inadequacy' and 'Chance', accounting for 48 per cent of the variance. Except for gender, demographic variables (age, educational level, social class) and variables specific to the sample in question (type of symptoms, length of participation in the programme) did not differentiate significantly subjects' beliefs about their illness. However, the findings suggest that lower ratings of personal inadequacy may be associated with increased optimism about subjects' future mental health. PMID- 1600407 TI - Personality disorders in panic with agoraphobia and major depression. PMID- 1600408 TI - Stress, coping and coping resources as correlates of adaptation in myocardial infarction patients. AB - A longitudinal study was conducted to examine the utility of a set of variables derived from the stress and coping literature as correlates of patients' level of psychosocial adaptation to a myocardial infarction. Forty patients participated in the study; data were collected soon after the patients' discharge from hospital and three months after the event. It was proposed that a high level of perceived stress associated with the infarct and the use of emotion-focused coping strategies would be associated with poor adaptation to the event, whereas the use of problem-focused strategies, high levels of self-efficacy and access to the appropriate personal (control beliefs, self-esteem and trait anxiety) and social (marital and family quality) coping resources were variables proposed to facilitate adaptation. There was only weak support for the proposed effects of perceived stress, and no support for the proposal that the use of problem-focused strategies would facilitate the adaptation of infarct patients. In contrast, the data provided some support for the hypothesized effects of self-efficacy and emotion-focused coping. There was also evidence to suggest that adaptation to an infarct was facilitated if subjects had internal control beliefs, high self esteem, low trait anxiety and high-quality family relations. Contrary to expectations, marital quality was largely unrelated to the measures of adaptation. PMID- 1600409 TI - Recovery from minor abdominal surgery: a preliminary attempt to separate anxiety and coping. AB - Using bivariate and canonical correlations, we investigated the dimensionality and post-operative correlates of indices which, we suggested, could be related to active cognitive coping in 40 patients undergoing minor abdominal surgery. Trait anxiety and pre-operative state anxiety were also measured; these intercorrelated, but each was independent of the putative coping measures. There were, however, intercorrelations amongst these questionnaires, which included the 'worry' scale of a coping checklist, Type A personality, pre-operative arousal and, in a negative direction, 'powerful others' health locus of control and pre operative stress. The dissociation between anxiety and the remaining measures emerged also in the post-operative correlates of these two dimensions. Whereas anxiety predicted poorer self-rated bodily state on the first post-operative day, the coping measures predicted a better state seven days post-operatively. PMID- 1600410 TI - Selective memory for sensory and affective information in chronic pain and depression. AB - Mood congruity effects in induced mood states and affective disorders are well established. Recent evidence suggests that a similar process occurs in chronic pain patients, although the extent to which the memory bias is a consequence of the affective or sensory state of the subject in this group is unknown. In this study selective memory for sensory and affective pain-related information was investigated in depressed and non-depressed chronic pain patients and depressed psychiatric patients. A recall test comprising sensory, affective and neutral adjectives matched for frequency was followed by a recognition task, where the words of the recall test were randomized with an equal number of new adjectives matched for word type and frequency. Comparison of the three patient groups with normal controls revealed specific recall biases directly related to pain and depression in both chronic pain groups and the controls. Contrary to expectations, the depressed psychiatric patients failed to show a recall bias for affective adjectives: the possibility of cognitive avoidance as an explanation for this is discussed. Signal detection analysis of the recognition results suggested that selective memory in chronic pain and depression may to some extent be accounted for by differences in 'true memory', the contribution of response bias remaining less clear. PMID- 1600411 TI - Autologous hemopoietic reconstitution after fetal liver infusion in patients with bone marrow failure: consequence or coincidence? AB - In the past 4 years we have treated four patients with a total of 19 fetal liver infusions (FLI). Two cases of refractory anemia with excess blasts in transformation (RAEB-t) were conditioned with cyclophosphamide and total body irradiation (1400 cGy) and were treated with FLI. In spite of such intensive conditioning, one patient recovered autologous hemopoiesis 3 weeks later, remaining in remission 4 years after this procedure. The second patient died with aplastic marrow on day 154, and the third suffered from severe aplastic anemia refractory to several types of conventional treatment. After FLI and without previous conditioning therapy a partial fetal engraftment was documented. This was transient and followed by autologous hemopoietic recovery and cure of the disease. The fourth patient had bone marrow failure in the setting of a severe pneumonia following autologous bone marrow transplantation. Ten days after FLI the hematological parameters dramatically improved and the pneumonia resolved. Autologous reconstitution of hemopoiesis was demonstrated. These experiences suggest that FLI might stimulate autologous hemopoiesis. This therapeutic approach may be useful to treat bone marrow failure when there is no response to first-line therapy. In hematologic malignancies with an indication for stem cell transplantation, other sources such as allogeneic or autologous bone marrow seem preferable to fetal liver cells. PMID- 1600412 TI - The cytotoxicity of alkyl-lysophospholipid on clonogenic leukemia cells and on normal bone marrow progenitor cells is highly, but differentially, increased by cryopreservation. AB - We studied the cytotoxic effect of alkyl-lysophospholipid (ALP) in combination with cryopreservation on human clonogenic leukemia cells from 10 patients with acute leukemia and on normal bone marrow progenitors (committed stem cells) from 10 donors, in order to assess the applicability of ALP as a purging agent in autologous bone marrow transplantation (ABMT). The tumoricidal effect of ALP was greatly increased by the cryopreservation procedure, both on leukemic progenitors and to a lesser extent on normal bone marrow progenitors. The cytotoxic effects of ALP and of cryopreservation were synergistic. As a consequence, the ALP dose for ex vivo purging has to be adjusted. Furthermore, the cryopreservation procedure itself is more cytotoxic for leukemic progenitors than for normal marrow progenitors, indicating that cryopreservation has a purging effect in AMBT. PMID- 1600413 TI - In vivo use of Campath-1G to prevent graft-versus-host disease and graft rejection after bone marrow transplantation. AB - Twenty-two patients (16 male, six female; median age 34 years, range 16-49) with acute myeloid leukemia (1st complete remission (CR), n = 9), acute lymphocytic leukemia (1st CR, n = 5), chronic myeloid leukemia (chronic phase n = 5, accelerated phase n = 1), malignant lymphoma (n = 1) and myeloma (n = 1) were transplanted with unmanipulated donor bone marrow after standard conditioning including the monoclonal antibody Campath-1G daily from day -4 to day 0. No further graft-versus-host disease (GVHD) prophylaxis was given. All patients engrafted and neither graft failure nor rejection were observed. Acute GVHD grade I (skin) was seen in 12 out of 21 patients at risk. Acute GVHD grade II (skin) occurred in two patients. Severe GVHD (grade III, IV) of the gut, liver and skin developed in two patients. The overall incidence of severe acute GVHD (II-IV) was 19% of the patients at risk. Chronic GVHD (skin only) was seen in eight patients (42%) (six of extensive severity). A total of 14 patients died, the causes being relapse (four), direct cytotoxic drug toxicity (one), a GVHD (two), disseminated varicella zoster (one), systemic tuberculosis (one), interstitial pneumonitis (three) and veno-occlusive disease (two). These results indicate that the intravenous administration of Campath-1G may have reduced the incidence of severe acute GVHD without the occurrence of graft failure. However, the incidence of chronic GVHD does not appear to have decreased. PMID- 1600414 TI - Serial cytogenetic studies in allografted patients with chronic myeloid leukemia. AB - Serial marrow karyotyping was performed in 31 chronic myeloid leukemia (CML) patients treated with allogeneic bone marrow transplantation (BMT). Of 11 hematological relapses, seven were heralded for up to 20 months by a cytogenetic relapse (characterized by increasing percentages of Philadelphia (Ph)-positive metaphases, seen on serial karyotypes). Chromosomal abnormalities additional to the Ph, seen before BMT, were not found again at relapse. Relapses were characterized by clonal evolutions of the Ph-positive cells, likely corresponding to cytogenetic patterns of treatment-induced leukemia [del(5q), del(7q), complex karyotypes] and were different from those generally found in CML evolution. Involvement of chromosome 1 was also frequent. Sporadic Ph-positive metaphases (not seen in repeated karyotypes) were seen only during the first 8 months after BMT. PMID- 1600416 TI - Meningitis due to penicillin-resistant Streptococcus pneumoniae in patients with chronic graft-versus-host disease. AB - Two episodes of meningitis due to penicillin-resistant Streptococcus pneumoniae occurring in two patients with chronic graft-versus-host disease (GVHD) are reported. Both patients were treated with ceftazidime. The first patient died, unresponsive to therapy. The second patient showed clinical improvement, reverting to her baseline mental status. This report draws attention to the fact that in chronic GVHD patients: (1) bacterial prophylaxis does not ensure protection against encapsulated bacteria; (2) rapid microbiological investigation is recommended with any upper respiratory tract infections. PMID- 1600415 TI - Second HLA-identical sibling transplants for leukemia recurrence. AB - We analysed data from 114 recipients of HLA-identical sibling transplants who relapsed and received a second transplant between 1978 and 1989. Twenty-nine patients had acute lymphoblastic leukemia, 46 acute myeloid leukemia and 39 chronic myelogenous leukemia. Median (range) interval between first and second transplants was 15 (1-80) months. Following the second transplant, graft failure occurred in 2%, acute graft-versus-host disease (GVHD) in 27% and chronic GVHD in 21% of patients at risk. Risks of interstitial pneumonia and hepatic veno occlusive disease were higher after the second than the first transplant. Two year probabilities (95% confidence interval) of treatment-related mortality, relapse and leukemia-free survival were 41% (30-53%), 65% (53-75%) and 21% (14 30%), respectively. Leukemia-free survival was 7% (2-19%) among patients relapsing less than 6 months after their first transplant, with high rates of both relapse, 77% (49-92%), and treatment-related mortality 69% (46-85%). In contrast, leukemia-free survival was 28% (19-41%) in those relapsing more than 6 months after the first transplant; in this group the probability of relapse was 59% (45-72%) and treatment-related mortality 30% (20-43%). Factors correlated with better outcome included a diagnosis of chronic myelogenous leukemia, relapse more than 6 months after the first transplant, acute leukemia in remission prior to the second transplant and good performance status. PMID- 1600417 TI - Chylothorax as a complication of central venous catheter-induced superior vena cava thrombosis. PMID- 1600418 TI - The future of biomedical communication; a symposium. I. Perspective from the editor of the British Medical Journal. PMID- 1600419 TI - Perspective from the editor of JAMA, The Journal of the American Medical Association. PMID- 1600420 TI - 1991 survey of recent health sciences library building projects. AB - Twenty health sciences libraries reported building planning, expansion, or construction of new facilities in the association's second annual survey of recent building projects. Six projects are new, freestanding structures in which the library occupies all or a major portion of the space. Six other projects are part of new construction for separately administered units in which the library is a major tenant. The final eight projects involve additions to or renovations of existing space. Seven of these twenty libraries were still in projected, predesign, or design stages of awaiting funding approval; of those seven, five were not prepared to release the requested information. Six projects are reported here as illustrative of current building projects. PMID- 1600421 TI - Impact of end-user search training on pharmacy students: a four-year follow-up study. AB - The Alfred Taubman Medical Library at the University of Michigan has offered instruction in online literature searching to third-year pharmacy students as a component of the course "Drug Information and Scientific Literature Evaluation" since 1983. In the spring of 1989, a follow-up study was conducted to assess the impact of instruction on four classes of graduates. Of a pool of 151 graduates, 90 (60%) responded to a mailed questionnaire on their use of information and computerized literature searching. The respondents were divided into four subgroups: end-user searchers, users of intermediaries, end users who used intermediaries, and those who did not use computerized literature search systems. Seventy-two percent of the respondents used some type of computerized literature searching, and 42% performed their own searches. The four subgroups differed in general computer use, familiarity with MEDLINE search terminology, information use, reasons for using or not using literature searching, and characteristics of searches (i.e., type, time frame, amount, and frequency). Training in end-user search systems appears to have had an impact on the continued use of computerized literature searching several years after the formal educational program. PMID- 1600422 TI - Evaluating library resources for accreditation: results of a study. AB - When the nursing collection at the University of Illinois Library of the Health Sciences was evaluated in 1990 for an accreditation self-study for the National League for Nursing, the evaluation was broadened to study resources, faculty participation in selecting them, and completeness of holdings. To evaluate holdings, lists were checked and conspectus and comparative statistical data were analyzed. Organization and collection development were also described, to document faculty input. User services and on-site and remote access were briefly reviewed to document how resources were made available. The results demonstrated that the library provided an acceptable level of support for nursing studies at the University of Illinois at Chicago. PMID- 1600423 TI - Medical knowledge for clinical problem solving: a structural analysis of clinical questions. AB - Despite technological advances that support wide-ranging access to and transfer of knowledge, practicing physicians continue to underutilize current biomedical literature. This paper explores the nature of clinically applicable medical knowledge through a structural analysis of clinical questions. The author analyzed a set of sixty questions, based on actual online search requests of practicing physicians, for stated and unstated needs, certainty levels, implicit and explicit assumptions, decision-making processes, and type of answer required. As a result, four states of information valuable in patient care were identified: prediagnostic assessment, diagnosis, treatment choice, and learning. These states are presented in frame-like structures that integrate declarative and procedural components of medical decision making. It is concluded that clinical problem solving requires a blend of declarative and procedural knowledge. The ratio depends, in part, upon the reasoning process underway at the time of the request. Procedural knowledge required for clinical problem solving may be absent from current biomedical journal literature or difficult to identify. PMID- 1600424 TI - Combining new technologies for effective collection development: a bibliometric study using CD-ROM and a database management program. AB - Librarians have used bibliometrics for many years to assess collections and to provide data for making selection and deselection decisions. With the advent of new technology--specifically, CD-ROM databases and reprint file database management programs--new cost-effective procedures can be developed. This paper describes a recent multidisciplinary study conducted by two library faculty members and one allied health faculty member to test a bibliometric method that used the MEDLINE and CINAHL databases on CD-ROM and the Papyrus database management program to produce a new collection development methodology. PMID- 1600425 TI - National Library of Medicine resource grants: application and review. AB - National Library of Medicine resource grants provide assistance in developing information services or activities, which are then made available to others. The resource grant program was redefined in 1989 to establish information access grants and information systems grants. The preparation of a resource grant proposal is discussed, with examples included for some sections. All applicants must use the PHS 398 application form, which is geared to research grants. The review process and reapplication are described. Problems with National Institutes of Health grant proposals that have been reported in the literature are discussed. PMID- 1600426 TI - The impact of the hospital library on clinical decision making: the Rochester study. AB - In these times of economic constraint, libraries of all types are under increasing pressure to evaluate their services. Hospital libraries face a particular challenge because the goals of the health care system demand that the relevance of library services to patient care be determined. The hospital librarians in Rochester, New York, responded to this challenge by developing a research project that explored the impact of library services on clinical decision making. A systematically sampled group of 448 physicians in the Rochester area agreed to participate in the study between September 1990 and March 1991. The physicians were asked to request some information related to a current clinical case and then to evaluate its impact on the care of their patients. Senior medical staff or administrators acted as study facilitators in each of the fifteen participating hospitals. As a result of the information provided by the library, 80% of the 208 physicians who returned their questionnaires said that they probably or definitely handled some aspect of patient care differently than they would have handled it otherwise. Changes in the following specific aspects of care were reported by the physicians: diagnosis (29%), choice of tests (51%), choice of drugs (45%), reduced length of hospital stay (19%), and advice given to the patient (72%). Physicians also said that the information provided by the library contributed to their ability to avoid the following: hospital admission (12%), patient mortality (19%), hospital-acquired infection (8%), surgery (21%), and additional tests or procedures (49%). The physicians rated the information provided by the library more highly than that provided by other information sources such as diagnostic imaging, lab tests, and discussions with colleagues. In addition to confirming earlier research findings that information provided by hospital libraries is perceived by physicians as having a significant impact on clinical decision making, the results increase our store of scientific knowledge about the specific nature and extent of the impact of information provided by the hospital library. PMID- 1600427 TI - The changing status of hospital libraries 1984 to 1989: characteristics and services in Region 7 of the National Network of Libraries of Medicine. AB - Economic and political factors have had far-reaching effects on hospital libraries in the last decade, but quantitative evidence of these changes is not readily available. Through periodic evaluation surveys within its multistate region, the Pacific Southwest Regional Medical Library Service, the Regional Medical Library for Region 7 of the National Network of Libraries of Medicine (formerly the Regional Medical Library Network) has monitored hospital library changes over the years. This paper compares data from a 1989 survey with similar information gathered in 1984. Longitudinal analysis was performed on responses from 188 hospitals that responded to both the 1984 and the 1989 survey, as was cross-sectional analysis of all responses from both surveys. Results showed a small decrease in the number of hospitals with separate library collections. Staffing patterns had changed considerably, with a drop of approximately one entire full-time salaried equivalent per library and a decrease in libraries managed by a librarian with an M.L.S. The libraries that provide all of a set of predefined core services and resources decreased from 61% in 1984 to 44% in 1989. Libraries with M.L.S. staff were more likely to have core services than those without professional staff. PMID- 1600428 TI - The use of independent information brokers for document delivery service in hospital libraries. PMID- 1600429 TI - Authorship outlets of academic health sciences librarians. AB - Journal articles are the most common publication format for U.S. academic health sciences librarians. This is consistent with the findings of other researchers. Of the total publications in this study, 68% were in journals. Watson found that 69% of the academic librarians' publications were published in some type of journal [8]. Similarly, Yerkey and Glogowski found that 67% of the publications in their study were journal articles, although their population consisted of all types of authors of library/information science materials [9]. Both the present study and Watson found that monographs were the second most common publication outlet. Watson found that 16% of the total publications were monographs; the current study identified 14.8% of the total publications as monographs [10]. Although Watson's findings are similar to the newer results, it is important to note that Watson's study was conducted in a different manner and included book reviews, which were not counted in the present study. The health sciences librarians in the present study published more than two thirds of their articles in library/information science journals and 27% in health sciences journals. Similarly, in Yerkey and Glogowski's study, the second-largest number of library/information science articles appeared in medical and health sciences journals [11]. Fang also found that 22.57% of the journal articles on health sciences librarianship or by health sciences librarians were in medical journals [12. This seems to demonstrate the desire of health sciences librarians to communicate with the health professionals. Yerkey and Glogowski that library and information science is an interdisciplinary field, "borrowing and supplying information to and from other disciplines"[13]. PMID- 1600430 TI - Expanded use of GaIN network for rapid dissemination of current clinical information. PMID- 1600431 TI - Bringing back the librarian, Part Three. PMID- 1600432 TI - Consistent improvement in the nutritional status of Colombian children between 1965 and 1989. AB - Three national anthropometric surveys carried out in Colombia in 1965-1966, 1977 1980, and 1986-1989 provide a reasonably standardized basis for comparing the nutritional status of infants and young children in those years. That comparison, presented here together with appropriate socioeconomic data, indicates marked reduction of malnutrition paralleling strong socioeconomic gains. PMID- 1600433 TI - Presence of Aedes (Gymnometopa) mediovittatus in Cuba: a new factor to be considered in the national campaign to eradicate dengue. AB - To assess the presence of the potential dengue vector Aedes mediovittatus relative to other mosquito species, data were examined from 44,199 larvitraps operating between January 1984 and December 1987 in the town of Mariel, Cuba. Of 1,068 larvitraps containing mosquitoes, 626 (58.6%) were positive for Ae. mediovittatus. Its relative presence increased each year except 1986, going from 37.9% of the positive traps in 1984 to 70.2% in 1987. More larvitraps were positive for Ae. mediovittatus than for Culex quinquefasciatus, which typically dominated breeding sites at the end of the intensive phase of the national campaign against Ae. aegypti in the early 1980s. The results appear to reflect Ae. mediovittatus' gradual infiltration into areas covered by the campaign, a factor that may need to be considered in efforts to control dengue in the Americas. PMID- 1600434 TI - Air pollution problems in Latin America. AB - Air pollution and associated health problems in Latin America are on the rise. This article provides an overview of conditions indicated by the admittedly limited data available, notes some of the present situation's health implications, and points out areas where air pollution data procurement and control measures could be improved. PMID- 1600435 TI - The epidemiology of breast-feeding in Mexico: rural vs. urban areas. AB - This article summarizes published and unpublished data on breast-feeding in Mexico collected between 1958 and 1987. These data suggest that Mexican rates of initiation of breast-feeding (78-83%) are among the lowest found in developing countries, that the median duration of breast-feeding in 1987 was virtually the same as it had been in 1976, and that about half of all Mexican infants are not breast-fed beyond six months of age. A finding that the duration of breast feeding was shortest in urban areas has important policy implications, since 72% of the population lives in urban zones. PMID- 1600436 TI - Comparison of three standards for evaluating fetal growth. AB - Three birth weight standards were applied to 1986 live births and neonatal deaths in Santiago, Chile, in order to ascertain how useful the 10th, 25th, 75th, and 90th percentile birth weights determined by these standards would be for selecting infants at high risk of neonatal death. This article reports the results of that study. PMID- 1600438 TI - Psychiatric disorders among emotionally distressed disaster victims attending primary mental health clinics in Ecuador. AB - Previous studies in developing countries have demonstrated post-disaster stress disorders in a substantial share of the people living through a natural calamity, but questions have remained as to the severity of these mental health problems. This article reports information derived from a 1987 study of Ecuadorian earthquake victims that shows many of the victims had diagnosable psychiatric disorders and provides insight into the nature of those disorders. PMID- 1600437 TI - Clinical and epidemiologic studies of Chagas' disease in rural communities of Oaxaca, Mexico, and an eight-year followup: II. Chila. AB - A seroepidemiologic survey conducted in 1971 in the rural Pacific coastal community of Chila in the Mexican state of Oaxaca showed an unusually high prevalence of antibody against the Chagas' disease agent Trypanosoma cruzi. Further studies were undertaken in 1973 and 1981 to (1) determine the pathologic impact of T. cruzi infection in humans, (2) investigate the natural history of the disease, (3) confirm that serologically positive persons were parasitologically positive, and (4) evaluate whether T. cruzi transmission continued into the next decade. This article reports results derived from those studies. PMID- 1600439 TI - The effect of sex education on teenagers in St. Kitts and Nevis. AB - Knowledge of sexual matters is one of several key factors capable of influencing teenage reproductive behavior. This article reports the results of initial and followup surveys designed to test such knowledge among adolescent students in St. Kitts and Nevis before and after they received a family life/sex education course in the mid-1980s. This course provided information about fundamentals of human reproduction and contraception, human growth and development, emotional development, and issues of adolescent sexuality. PMID- 1600441 TI - Industrial and vehicular contamination in Central America. PMID- 1600440 TI - Status of the eradication/elimination of certain diseases from the Americas. PMID- 1600442 TI - World AIDS day 1991 observances urge sharing the challenge. PMID- 1600443 TI - New children's vaccine initiative launched. PMID- 1600444 TI - Drug therapy of rheumatic diseases during pregnancy. PMID- 1600445 TI - Lung involvement in systemic sclerosis. PMID- 1600446 TI - Obesity and osteoarthritis of the knee. PMID- 1600447 TI - Tomb, temple, machine and self: the social construction of the body. AB - The body is socially constructed; and in this paper we explore the various and ever-changing constructions of the body, and thus of the embodied self, from the Greeks to the present. The one word, body, may therefore signify very different realities and perceptions of reality; and we consider briefly how and why these meanings changed. Plato believed the body was a 'tomb', Paul said it was the 'temple' of the Holy Spirit, the Stoic philosopher Epictetus taught that it was a 'corpse'. Christians believed, and believe, that the body is not only physical, but also spiritual and mystical, and many believed it was an allegory of church, state and family. Some said it was cosmic: one with the planets and the constellations. Descartes wrote that the body is a 'machine', and this definition has underpinned biomedicine to this day; but Sartre said that the body is the self. In sum, the body has no intrinsic meaning. Populations create their own meanings, and thus their own bodies; but how they create, and then change them, and why, reflects the social body. PMID- 1600448 TI - Tendo Achillis pain: steroids and outcome. AB - A retrospective study is presented of 83 athletes with tendo Achillis pain (TAP) treated conservatively over a 12-year period from 1976 to 1988. Local steroid injections did not contribute to an earlier return to sport, though many individuals were improved symptomatically. Local steroids were not found to have a deleterious effect on outcome. Steroids were used most frequently in the chronic cases that presented late and had been treated previously: this group had most recurrences and surgical intervention. One case of Achilles rupture (3%) occurred in the group treated with steroids. Early presentation for treatment led to an earlier return to sport and avoidance of recurrences. Recurrences were most frequent in athletes with bilateral Achilles tendinopathy. The tendo Achillis lesion may range from peritendinitis through a mixed lesion of the tendon and paratenon, to complete rupture. The management depends upon accurate diagnosis, its chronicity and the age and aspirations of the patient. Steroids are safe to use and further prospective trials should note presentation time and disease staging accurately. PMID- 1600449 TI - Sports medicine in New Zealand. AB - Sports medicine in New Zealand is characterized by a team approach. Experienced professionals work together to the benefit of athletes, be they elite performers or those in sport for purely recreational purposes. A no-fault accident compensation scheme is used to provide speedy access to treatment services for those injured in sport and also for advice on accident prevention. Recent initiatives include a task force on drugs in sport and the creation of regional sports foundations. Sports medical education is a prominent part of the New Zealand scene. PMID- 1600450 TI - Fall in skin temperature of exercising man. AB - Fall in skin temperature during initial muscular work was investigated in ten healthy men. Bicycle exercise was performed at workloads of 50-150 W in a climatic chamber at ambient temperatures of 10-40 degrees C (relative humidity 45 55%). Skin temperatures at seven or eight points over the body surface were measured using thermography and thermocouple recording systems. Sweat rates were significantly higher at 40 degrees C than at 30 degrees C, whereas the fall in skin temperature was almost equal. The reduction of skin temperature during exercise was the same throughout the year, although sweat rate was significantly higher in summer than in winter. In coloured thermographics of the skin temperature distribution during exercise of both 50 and 150 W at 10 or 20 degrees C, the skin temperature began to decline immediately at the onset of the exercise. Increased work intensities reduced skin temperature. The results suggest that fall in skin temperature during initial exercise was not due to increased evaporative cooling but to vasoconstriction, probably caused by non thermal factors. PMID- 1600451 TI - A comparative study of the metabolic effort expended by horse riders during a jumping competition. AB - The three main Olympic horse riding disciplines are dressage, jumping, and three day eventing (including dressage, cross country and jumping). In the jumping discipline (obstacle race), the 'team' (horse rider) is judged under the different conditions that might take place in a varied run. The horse is expected to show power and ability; the rider must show riding skill and good physical condition. However, the different conditions encountered by the rider during competition (duration of event, continuous isometric working level, especially in the inferior trunk, lead us to consider the need for a rider to develop different metabolic pathways to meet the high energy requirements of the competition. PMID- 1600452 TI - Maximal oxygen uptake in trained and untrained 15-year-old boys. AB - The purpose of this study was to assess maximal aerobic power (VO2max) in trained and untrained 15-year-old boys. The trained subjects (18) were junior swimmers from a Belgrade swimming team, and the untrained ones (12) were from a Belgrade high school. VO2max was directly measured during progressive cycle ergometer exercise using open circuit spirometry. No significant differences in height, mass, percentage fat and vital capacity were noted between the trained and untrained groups. Maximal aerobic power (overall, relative and in relation to lean body mass) in absolute values, and expressed per kilogram of body mass and lean body mass, was 31.5%, 21.2% and 20.6%, respectively, higher in the trained than in the untrained group (P less than 0.05). These data suggest that physical training significantly increases maximal aerobic power in young subjects. PMID- 1600454 TI - 20-MST and PWC170 validity in non-Caucasian children in the UK. AB - The validity was investigated of 20-MST (20 Metre Endurance Shuttle Run Test) and PWC170 (Physical Working Capacity) field tests with laboratory-measured peak oxygen uptake (VO2peak) in a multiracial UK population of 12-year olds: 103 subjects completed the 20-MST and 96 of these completed the PWC170. To assess validity, a laboratory treadmill test was completed by ten boys and ten girls who had performed both field tests. VO2peak was 43.8 ml kg-1 min-1 for boys and 38.5 ml kg-1 min-1 for girls. Pearson product-moment correlation showed 20-MST to be a reliable measure of cardiorespiratory fitness (r = 0.83, boys; r = 0.76, girls, P less than 0.03), while correlations with PWC170 were lower (r = 0.64, boys; r = 0.54, girls) and not significant. The 20-MST was consistent in retest (n = 20) - reliability coefficients r = 0.73, boys; r = 0.88, girls; P less than 0.01. The results suggest 20-MST is a valid, measure of fitness in this population when compared with VO2peak. PWC170 is less valid, possibly due to cultural and social backgrounds. The cycle test was inappropriate in this population, especially for girls unaccustomed to exercise and cycling. The 20-MST test is recommended for large groups of children when facilities are limited. It requires limited skill or habituation and is relatively non-invasive. PMID- 1600453 TI - The effects of a university fitness programme on health-related variables in previously sedentary males. AB - This study reports on the effects of a 10-week university fitness programme on health-related fitness variables. Twenty-one male exercisers, aged 37.0(10.3) years (mean(s.d.); range 21-58), and 22 male controls, aged 38.6(7.9) years (mean(s.d.); range 17-54), volunteered to take part. Two sample t-tests and 95% confidence intervals were used to determine if the exercise group demonstrated a greater average improvement than the control group and the average improvement in both groups separately. The exercise group showed a greater average improvement over the controls from Test 1 (before fitness programme) to Test 2 (after) in the following: steady-state heart rate (beats min-1) 95% confidence intervals (-7.8, 16.2); predicted VO2max (ml kg-1 min-1): 95% confidence intervals (3.2, 6.6); sit ups (repetitions): 95% confidence intervals (3.1, 7.0); flexibility (cm): 95% confidence intervals (3.3, 6.9). There was no significant difference between the exercise group and control group in body weight, percentage body fat, blood pressure, total plasma cholesterol, high-density lipoprotein and triglycerides. The exercise programme improved aerobic fitness, local muscular endurance and flexibility. However, the increase in aerobic fitness did not coincide with beneficial changes in the coronary risk profile. PMID- 1600455 TI - First-aid supplies for backpacking. AB - A portable first-aid kit should be carried in the backpack of campers, hikers, and anyone who expects to spend time in a remote and unoccupied area. That is the recommendation found in lay texts dealing with medical care, in backpacking books, as well as in articles appearing in popular magazines. It goes without saying that it is far better to practise safety and prevention than to have to use first aid. However, many times medical problems occur which no amount of safety and forethought could have prevented. Information in this paper indicates that hikers are generally well prepared for the health-related problems they encounter. Hikers carry diverse supplies to meet health problems but there are some basic supplies with which hikers start their long-distance sojourn. Those supplies and their usage rates are discussed, as are attitudes toward using the supplies. PMID- 1600456 TI - Morphological effects of mechanical forces on the human humerus. AB - Various mechanical forces produce a variable stimulus intensity on bone and have different effects on its growth and development. The aim of this project was to study the effects of a variety of mechanical forces on human humerus morphology. This was investigated by measuring the cortical thickness (cm) and diameter (cm) of the humerus at its proximal, middle and distal thirds from radiographs. The humerus of each of 46 men (five controls, six swimmers, eight gymnasts, seven javelin throwers, nine discus throwers and 11 weightlifters) was radiographed on both right and left sides. The humerus size variation among the participants, in order of increasing size, was found to be as follows: gymnasts, controls, swimmers, javelin throwers, weightlifters and discus throwers respectively. The humeral cortex was largest in the weightlifters, being significantly (P less than 0.05) thicker at distal, medial and proximal sites. The proximal and distal humeral sites in javelin and discus throwers were significantly thicker than those of the control subjects. From the results, static load would seem to provide a higher stimulus to bone than dynamic loading. PMID- 1600458 TI - Stroboscopic computerized determination of humeral rotation in overarm throwing. AB - Analysis of the final phase of the overarm handball throw was carried out by a microcomputerized treatment of photographic images taken simultaneously in two grid layouts. Reflective stickers on the joints of the throwing arm (shoulder, elbow, wrist) allowed the coordinates of these three points to be measured against a reference on the wall. Using a mathematical treatment and Euler matrices, the movement could be studied in space. The results confirmed that humeral rotation occurs during the overarm handball throw. Initial external rotation was immediately followed with internal rotation about 40 ms before ball release. PMID- 1600457 TI - Adenosine in exercise adaptation. AB - By influencing the regulation of the mechanisms of angiogenesis, erythropoietin production, blood flow, myocardial glucose uptake, glycogenolysis, systolic blood pressure, respiration, plasma norepinephrine and epinephrine levels, adenosine may exert a significant effect on the body's adaptation response to exercise. However, adenosine's possible influence over the vasodilatory response to exercise in skeletal muscle is controversial and more research is required to resolve this issue. Various popular exercise training methods, such as cyclic training, interval training, and the 'warm down' from training may increase adenosine levels and thereby might enhance the response of adenosine-influenced adaptive mechanisms. Among the several classes of drugs which may enhance extracellular adenosine levels and thereby might augment adenosine-influenced adaptive mechanisms, are the anabolic steroidal and some readily available non steroidal anti-inflammatory drugs (NSAIDs). PMID- 1600459 TI - A survey of golf injuries in amateur golfers. AB - A survey of 461 amateur golfers was undertaken to assess golf injuries. There were 193 respondents of whom 57% reported injuries. Wrist, back, muscle, elbow and knee problems were the most likely ailments to compromise a player's game. Overuse and poor technique were the main aetiological factors. Attention to those factors in addition to maintenance of physique would reduce the incidence of these problems. PMID- 1600460 TI - Changes in blood glucose levels during a 1005-km running race: a case study. AB - The blood glucose response of a male ultramarathon runner was monitored throughout a 1005-km race. Before the race the runner had a fasting blood glucose concentration of 5.1 mM. At no stage during the race were his mean blood glucose levels less than 5.8 mM. This was partially attributed to the eating patterns of the athlete, the times at which blood samples were taken, the glycaemic index of food ingested and hyperglycaemia. While there was no evidence of glucosuria, ketones were present in the urine on one day of the event. There were other signs suggesting that at various stages of the event the runner had a metabolic acidosis. Possible reasons for this are discussed. PMID- 1600462 TI - [Electrophoresis study of hemocyanin of the polytypic species Idotea chelipes and Idotea balthica basteri (Crustacea Isopoda)]. AB - Hemocyanin has been used as a protein marker for Crustacea speciation. The specificity of the hemocyanin fractions of two Idotea species has been confirmed by mono and bidirection electrophoresis. Four protein fractions have been found in the two Idotea species. However, the molecular weight of each Idotea chelipes fraction is slightly higher. The two fractions of high molecular weight are strongly associated. We assumed a molecular weight of 240,000 for I. chelipes and 230,000 for I. balthica basteri. The two other protein fractions are well separated and have a weight of 130,000 and 77,000 in I. chelipes; 120,000 and 75,000 for I. b. basteri. In contrast, the subspeciation of I. chelipes has not been clearly demonstrated by electrophoresis of the hemocyanin. PMID- 1600461 TI - Partial and complete ruptures of the Achilles tendon and local corticosteroid injections. PMID- 1600463 TI - [Characterization of secondary vitellin in the crustacean Brachyura Carcinus maenas]. AB - The secondary vitellin was chromatographically purified and characterized in the crab, Carcinus maenas. It was a lipoglycoprotein of molecular weight 500,000. After dissociation, we observed two major sub units (82,000 and 72,000, respectively), and many lighter minor fractions. These results are compared with those described for some other Crustacea. PMID- 1600464 TI - Using Lotus software to calculate faculty merit increases. AB - Evaluation of college and university faculty is an annual occurrence in most institutions. The evaluation process is time consuming and may not result in the desired outcome: a discriminating, objective, and comprehensive evaluation of faculty performance. Merit increases are based on the results of faculty performance evaluations. The lack of precision and the complexity of the process supports the adoption of a computer-based approach to calculate faculty merit increases. Lotus is a powerful and sophisticated software program that supports the organization, analysis, and reporting of large amounts of information. This article describes the process for developing a computer spread sheet system for calculating faculty merit increases. PMID- 1600465 TI - A database design for community health data. AB - The ability to collect, store, and retrieve community health data is critical to providing health services in a timely and efficient manner. With the widespread availability of computer hardware and software that can assist in this process, the task is becoming easier. One important tool is the database management system (DBMS). A DBMS provides a conceptual framework to assist in organizing data and software that can physically store, maintain and retrieve data. The most popular DBMSs available today support the Relational Data Model, which has a conceptual framework that provides for the organization of data in tables. The authors present a database design, using the Relational Data Model, for a database of community health data. PMID- 1600466 TI - Designing a patient care medication and recording system that uses bar code technology. AB - Bar code technology has been implemented in a variety of health care applications to facilitate computerized data entry. In this report, the author describes the potential application of a patient medication administration and recording system that uses bar code technology for data entry. The need for nursing to collaborate with pharmacy and information systems developers is discussed, and issues for consideration in the design of the medication system are outlined. PMID- 1600468 TI - Statistics in nursing and allied health education and literature: some comments and a selected bibliography. PMID- 1600467 TI - A microcomputer-based information management system for a nurse-managed clinic. AB - A project team from a nurse-managed health care center designed and used a microcomputer-based information management system to document the activities of their clinic. Commercial software, dBase III Plus, was used to program the system, called Nurse Education Link to Aged Center (NELAC). NELAC reflects the center's philosophy of helping clients attain maximum satisfaction of their health care needs through self care. NELAC's specific purposes include 1) matching student nurses with potential clients for clinical experiences; 2) providing an efficient reminder system to improve follow-up care for clients; 3) maintaining longitudinal client records; 4) producing reports of services and activities of the center; and 5) providing aggregate data for research. PMID- 1600469 TI - The effect of methacholine and histamine on cyclic AMP-dependent protein kinase activity in the guinea-pig isolated trachea. AB - The effects of methacholine and histamine were examined on cyclic AMP-dependent protein kinase (A-kinase) activity in guinea-pig isolated trachea, using kemptide as a substrate for phosphorylation during the determination of the enzyme activity. Methacholine (EC90, 10 microM) induced a rapid reduction in the basal A kinase activity ratio, which was maximal after 30 s. This initial reduction coincided with the early phase of isometric tension development, and returned to control levels 4 min after the addition of methacholine. Pretreatment with atropine inhibited the methacholine response. In contrast, histamine (EC90, 30 microM) was without effect upon A-kinase activity ratio. The results establish the sensitivity of the A-kinase assay using kemptide and demonstrate that not all contractile agonists have the capacity to inhibit basal activity of A-kinase in airway smooth muscle. PMID- 1600470 TI - ATP-MgCl2 restores renal microcirculation following trauma and severe hemorrhage. AB - Although ATP-MgCl2 enhances the recovery of renal function after ischemia and reperfusion, it is not known whether this agent has any beneficial effects on renal microcirculation and function in a nonheparinized model of trauma and severe hemorrhage. To study this, a midline laparotomy was performed (i.e., trauma induced) and the rats were bled to and maintained at a mean arterial pressure of 40 mmHg (1 mmHg = 133.32 Pa) until 40% of the maximum shed blood volume was returned in the form of Ringer's lactate (RL) solution. Animals were then resuscitated with 4 times the volume of the shed blood in the form of RL. ATP-MgCl2, 50 mumol/kg body weight, or an equivalent volume of saline, was infused intravenously during and following resuscitation. Renal microcirculation was examined by using colloidal carbon infusion and laser Doppler flow-metry. Glomerular filtration rate (GFR) was assessed with [3H]inulin clearance and cardiac output (CO) was determined by dye dilution technique. The results indicate that the depressed renal microcirculation following hemorrhage and resuscitation was restored by ATP-MgCl2 treatment. GFR was significantly higher in ATP-MgCl2-treated than saline-treated rats. ATP-MgCl2 also increased urine output, restored the decreased CO, and prevented the occurrence of renal edema after hemorrhage and resuscitation. Thus, ATP-MgCl2 appears to be a useful adjunct to crystalloid resuscitation following trauma and severe hemorrhagic shock even in the absence of blood resuscitation. PMID- 1600471 TI - Influence of various mixtures of inhaled toluene and xylene on the biological monitoring of exposure to these solvents in rats. AB - The present study was undertaken to describe the influence of simultaneous exposure by inhalation to toluene and xylene on some aspects of their respective metabolic disposition. Adult male rats were exposed acutely (5 h) to 75, 150, and 225 ppm of toluene or xylene and to various mixtures of these solvents: toluene (75 ppm) and xylene (225 ppm), toluene (150 ppm) and xylene (150 ppm), toluene (225 ppm) and xylene (75 ppm). Compared with single exposure, simultaneous exposure resulted in lower amounts of excreted hippuric acid (20-30%) and methylhippuric acids (4-40%) in urine over a period of 24 h, even though significant differences were seen only with the toluene (150 ppm) and xylene (150 ppm) combination. In addition, increased concentrations of solvents in blood (toluene, 230%; xylene, 500%) and in brain (toluene, 230%; xylene, 320%) were found during the immediate post-exposure period. Simultaneous exposure also enhanced the pulmonary elimination of both solvents (toluene, 190-240%; xylene, 340-650%). Influence of repeated simultaneous exposure (9 days) was investigated for the toluene (150 ppm) and xylene (150 ppm) combination and the results compared with those of repeated exposure to each solvent administered singly. Under these conditions, repeated simultaneous exposure decreased the excretion of urinary metabolites, but only after the first exposure. On the other hand, simultaneous exposure resulted in significantly higher concentrations of toluene (210%) and xylene (240%) in blood throughout the entire 9-day exposure period. These results strongly suggest mutual metabolic interactions (inhibition) between toluene and xylene that affect the metabolic disposition of both solvents and ultimately the biological monitoring of data of exposure to a combination of solvents in rats. PMID- 1600472 TI - The effects of dopamine on prolactin mRNA levels in rat pituitary cells in culture. AB - Dopamine is known to be the prolactin-release inhibiting factor, but the effects of dopamine itself on regulation of prolactin messenger RNA have been little studied because of the instability of dopamine. We have compared the effects of dopamine and bromocriptine on the levels of prolactin mRNA and on the rates of synthesis, storage, and release of prolactin in primary cultured rat pituitary cells. The cells were incubated for 72 h with no secretagogue (control group) or in the presence of either dopamine (10 mumol/L) plus ascorbic acid (100 mumol/L) or bromocriptine (0.1 mumol/L). Prolactin mRNA was measured in cell extracts by means of slot blots, and newly synthesized prolactin was measured in similar incubations by the addition of [3H]leucine, followed by gel electrophoresis. The levels of total prolactin were measured by radioimmunoassay. Prolactin mRNA was reduced to 78 +/- 9% (mean +/- SEM) of control levels in bromocriptine-treated cells and to 59 +/- 7% in dopamine-treated cells, demonstrating that dopamine stabilized by ascorbic acid was able to reduce the levels of prolactin mRNA in rat pituitary cells in culture. Dopamine may act at sites in addition to the dopaminergic D2 receptor, since the level of prolactin mRNA was reduced more by a supramaximal dose of dopamine than by a supramaximal dose of bromocriptine. The results of the [3H]prolactin and prolactin measurements suggested that availability of mRNA was not a major factor in controlling the rate of prolactin synthesis. PMID- 1600474 TI - Psychiatric disorders in late life. PMID- 1600473 TI - Metabolism during normoxia, hyperoxia, and recovery in newborn rats. AB - Aerobic metabolism (oxygen consumption, VO2, and carbon dioxide production, VCO2) has been measured in newborn rats at 2 days of age during normoxia, 30 min of hyperoxia (100% O2) and an additional 30 min of recovery in normoxia at ambient temperatures of 35 degrees C (thermoneutrality) or 30 degrees C. In normoxia, at 30 degrees C VO2 was higher than at 35 degrees C. With hyperoxia, VO2 increased in all cases, but more so at 30 degrees C (+20%) than at 35 degrees C (+9%). Upon return to normoxia, metabolism readily returned to the prehyperoxic value. The results support the concept that the normoxic metabolic rate of the newborn can be limited by the availability of oxygen. At temperatures below thermoneutrality the higher metabolic needs aggravate the limitation in oxygen availability, and the positive effects of hyperoxia on VO2 are therefore more apparent. PMID- 1600475 TI - Epidemiology of geriatric affective disorders. AB - Recent Epidemiologic Catchment area studies found the prevalence of major depression to be only about 1% in community-dwelling elders; other less severe depressive disorders, however, may be present in over 25% of this population. Furthermore, at least 8000 persons over age 60 commit suicide each year, making up nearly one quarter of the total number reported, a rate much higher than expected given the proportion of elderly in the US population. Bipolar disorder, on the other hand, is much less common than unipolar depression at a rate of about 0.1% in the community; in nursing homes, however, as many as 10% of residents may have this condition. Sociodemographic correlates of depression in late life include female sex, divorced or separated marital status, low income or educational level, inadequate social support, and recent negative and unexpected life events. In particular, physical health has a major impact on mood and well being; consequently, rates of major depressive disorder in elders hospitalized with medical illness are over 10 times that reported in the community. PMID- 1600476 TI - Psychobiologic features of geriatric affective disorder. AB - Limited work has been done specifically assessing psychobiologic features of depression in the elderly. The biologic characteristics discussed in this article generally discriminate depressed from nondepressed groups in older as well as in younger groups, but they often are not specific for depression and occur in other disorders as well. These markers are not currently useful to make a standard clinical diagnosis in that they lack sufficient sensitivity and specificity. Limitations in this research include the fact that depression is defined phenomenologically, not biologically, and the failure to explicitly study depressive subtypes associated with aging. Other limitations involve the use or reporting of only one biologic characteristic and the lack of knowledge of the pathophysiologic or functional significance of that characteristic. It is likely that some markers identify particular biologic characteristics that may be overrepresented in groups of depressed patients compared with the general population. For example, decreased platelet imipramine-binding density or decreased CSF 5-HIAA may characterize individuals with relative serotonin system deficits who may be at increased risk for depression or suicide or have symptoms related to depression. Or, increased platelet alpha 2-receptor binding or increased EEG alpha may identify individuals who possess noradrenergic or arousal defects associated with depression. The majority of these studies are based on cross-sectional assessments during an acute phase of illness or at death. Longitudinal studies are needed to assess test-retest reliability, state versus trait, and other characteristics. An adequate understanding of the psychobiology of depression in the elderly must address age effects, potential depression subtypes, and age of onset, and finally, it must explain adequately how the biology is related to the depression. PMID- 1600477 TI - Imaging and affective disorder in the elderly. AB - Changes in brain structure have been demonstrated in elderly patients suffering affective disorder. Enlarged ventricles are associated with cognitive impairment and higher mortality. Depressed subjects also may show a greater degree of cortical atrophy and subcortical white matter, and basal ganglia lesions seem to be commoner than in age-matched controls. The abnormalities demonstrated are not as severe as those found in degenerative dementias such as Alzheimer's disease, and at present there is no evidence to suggest they are progressive. There is a convincing association with vascular disease, although further neuropathologic correlates are needed. Functional imaging methods are just beginning to be applied to elderly populations and, in affective disorder, findings are similar to those in younger patient groups. The results from different groups vary due to technologic differences and the clinical heterogeneity of the patients studied. Depression, however, may be accompanied by decreased and mania by increased cerebral blood flow or metabolism. Evidence also appears to be mounting of a state-dependent frontostriatal dysfunction in depression. Challenges for the future include replicating such results using larger diagnostically homogeneous patient groups and differentiating the findings from those in other disorders such as schizophrenia and basal ganglia disorders. PMID- 1600478 TI - Depression and physical illness in the elderly. AB - The authors' study confirmed the high prevalence of depressive symptoms in elderly medical inpatients but found no relationship between the diagnosis of or symptoms of depression and mortality or hospital use. Other studies examining the impact of depression on outcome for elderly patients may not have adequately controlled for the severity of the accompanying physical illness, which may perhaps have been responsible for the reported adverse effects of depression on outcome. An alternative explanation is that the authors' study involved a 1-year follow-up and a longer period of time may be necessary. The study demonstrated that routine screening for depression in acute elderly medical inpatients may be a useful way of detecting coexisting psychiatric morbidity. The routine screening measures were acceptable to patients and may be of considerable potential value in alerting staff to accompanying psychological distress. This study also illustrated the high prevalence of depression in patient samples and the importance and usefulness of screening geriatric inpatients. There are, however, several questions that remain unanswered both in studies reviewed in this article and in the authors' own work. The etiology and mechanism of the association between physical illness and depression are unknown, and there has been a dearth of studies assessing the feasibility and utility of specific treatments for depression in the elderly physically ill. PMID- 1600479 TI - Depression, dementia, and reversible dementia. AB - This article reviews the syndromic concepts of depression and dementia and the concurrence of these common entities. In DAT, depression appears to be a reversible source of excess disability, amenable to pharmacologic as well as environmental interventions. In the vascular dementias, depression appears to be a specific complicating feature, in which localization of the lesion plays a significant role. The abulic state should not be mistaken for a depressive syndrome, although its presence should alert the clinician to evaluate for dementia and depression. Depression is especially prevalent in the subcortical dementias. Future studies using dynamic neuroimaging will help define the limits of this important concept. Reversible forms of dementia are much less common than previously suspected. The clinician's task is to identify causes of excess disability due to superimposed illnesses while avoiding diagnostic or therapeutic nihilism. The appropriate use of medication and the ongoing surveillance for adverse drug reactions are the foremost tasks of today's clinician treating the elderly patient. PMID- 1600480 TI - Geriatric delusional depression. AB - Delusional depression frequently is encountered in the treatment of older psychiatric patients. Although the pathogenesis of this disorder and its relationship to organic brain lesions remains unclear, somatic treatment, especially with ECT, leads to initial recovery in the majority of cases. High rates of relapse and the possibility of increased mortality in these patients argue for studies of the effectiveness of maintenance treatments. PMID- 1600481 TI - Depression in nursing home residents. AB - Although their extent remains unclear, major and minor depressions are widespread in the nursing home population. This statement appears intuitively to be correct when consideration is given to the inactivity, decline in functional competence, loss of personal autonomy, and unavoidable confrontation with the process of death and dying that are associated with nursing home placement. In addition, some nursing home residents have had previous episodes of depression or are admitted to the facility already dysthymic or with other chronic forms of the illness. Such circumstances provide a favorable culture for the development and persistence of depressive illness. When the high frequency of other psychiatric disorders among nursing home residents is factored in, it is not surprising that long-term health care facilities have come to be regarded as de facto psychiatric hospitals. Nursing homes largely lack the treatment resources of psychiatric hospitals, however. Nursing home physicians are often unprepared to make psychiatric diagnoses, and a perfunctory annual psychiatric evaluation is insufficient to manage the complex depression syndromes of nursing home residents. Because nursing home psychiatrists typically work on a consultation basis, recommendations are not necessarily acted upon by the primary physicians. The consequences of undiagnosed and untreated depression are substantial. From the psychiatric perspective, the possibility that depression increases the risk for eventual development of permanent dementia highlights the importance of early identification for cases of reversible dementia. From the rehabilitation point of view, persistent depression among individuals with physical dependency following a catastrophic illness is associated with failure to improve in physical functioning. Depression can probably be linked to increased medical morbidity in nursing home residents, a relationship that also has been suggested for elderly medical inpatients. If so, the use of nursing time and other health-care facility services would be greater for depressed than nondepressed residents, and financial costs would be higher as well. Finally, recent data point to increased mortality in nursing home residents with major depressive disorder. It is apparent that depression in long-term care facilities is a condition with doubtful prognosis and negative medical, social, and financial consequences. The highest costs of all may be paid by nursing home residents who experience the unrelieved suffering of depressive illness. Only epidemiologic research using standard diagnostic criteria and direct resident assessment will adequately establish the magnitude of the need for intervention among depressed residents in long-term care.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1600482 TI - Using tricyclic antidepressants in the elderly. AB - Only a few of the eight tricyclic antidepressants available today have been studied systematically in the elderly. Tertiary amine tricyclics such as amitriptyline and imipramine have been reported to be effective in depressed geriatric patients, but because of their potential for side effects, it is not advisable to use them in the elderly. Desipramine has a less toxic side effect profile, especially with respect to anticholinergic effects, but its efficacy has not been well studied. This does not mean, however, that it is not an effective drug for the elderly depressed. Nortriptyline is the tricyclic that has been the most studied. The results of those studies show that it should be recommended as an antidepressant for older patients. It is effective in both the acute and continuation treatment of depression in the elderly. As far as its use in maintenance treatment, the results are mixed but at this moment there is nothing with which to compare it. It has a favorable side effect profile: low anticholinergic activity; relatively few cardiac side effects, even in patients with preexisting cardiac disease; and relatively less orthostatic hypotension. Nortriptyline also has the virtue of an established therapeutic range for its steady-state plasma level. The role of its 10-hydroxy metabolite needs to be further explored, but when its contribution to efficacy and toxicity is better understood, it may be possible to use nortriptyline in a more precise and safe way in elderly patients. The bulk of evidence suggests, partly by default, that nortriptyline should probably the tricyclic-of-first-choice in treating an elderly patient with major depression. PMID- 1600483 TI - Monoamine oxidase inhibitors and atypical antidepressants. AB - The following conclusions may be drawn from this article: 1. The age at which subjects are considered "elderly" or "geriatric" varies from study to study. By convention, age 65 is usually taken as the minimum age, yet virtually all studies cited included subjects below 65. Indeed, in a majority of studies, most of the subjects were below the conventional age of 65. Defining the minimum age for geriatric psychopharmacology studies is particularly important because there may be considerable pharmacodynamic and pharmacokinetic heterogeneity in people aged 65 and older. Clinical experience suggests that patients below age 80 tend to respond to medications like late middle-age adults, whereas those above age 80, as a group, are more sensitive to drugs. Because people 80 and above constitute the fastest growing group of Americans, it is essential to conduct more therapeutic clinical trials using them as research subjects. Information gathered from persons aged 60 to 79 may not be relevant to this older age group. 2. The total number of individuals studied in carefully controlled, double-blind research studies of MAOIs, atypical antidepressants, or psychomotor stimulants are relatively few when compared with the number of individuals studied with tricyclic antidepressants, or the number of nonelderly subjects studied. 3. Although many older persons are included in mixed-age research populations, the number of studies specifically designed in the elderly is also remarkably few. 4. In those studies that did focus on older patients, the definition of elderly was extended "downward" to include patients at age 55, or even 50. Whether or not this was done in order to enhance research subject recruitment, the net result is to vitiate any overall conclusion regarding the efficacy of drugs in patients over age 65, the usual lower cutoff for "elderly" or "geriatric" definition. 5. With the exception of a handful of patients receiving fluoxetine and methylphenidate, virtually no research patient above the age of 80 has been studied using any of the compounds discussed in this article. 6. Some of the double-blind studies reviewed are more than a decade old and techniques in research design have changed substantially since those studies were conducted. Many of the earlier studies would not be acceptable according to contemporary research design criteria because of inappropriate or inadequate inclusion criteria, inappropriate or inadequate outcome criteria, and inappropriate or inaccurate diagnostic criteria.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1600484 TI - The use of electroconvulsive therapy in geriatric patients. AB - The use of ECT has had a resurgence in the past decade as the promise of more effective and specific pharmacotherapy has been unfulfilled. This has been especially true in the elderly in whom ECT has been frequently demonstrated to be a safe and effective intervention. The decision to use ECT in an elderly patient is a complex one, based on the patient's illness, risks of the treatment compared with alternate or no treatment, and patient and family wishes. The list of dogmatic "absolute contraindications" for ECT has been replaced with a pragmatic philosophy looking at risk/benefit ratios. Such an attitude can only serve to enhance the quality of care clinicians provide their patients. PMID- 1600485 TI - Psychotherapy with elderly depressed patients. AB - Although psychotherapy outcome research is not without controversy, available evidence suggests that elderly patients benefit from an active, structured relationship with a therapist who provides a helpful therapeutic setting for comprehending and mastering problems that contribute to depression. Until research can evaluate better the various types of therapies, it is reasonable to integrate aspects of different therapies in the clinician's approach to depressed elderly patients, depending on the clinician's understanding of the patient's diagnosis, ego strengths and weaknesses, and capacity to cope and change. The therapist can use psychodynamic, cognitive, behavioral, interpersonal, and supportive techniques in a flexible manner, individualizing therapy to meet the patient's specific needs. Antidepressants are helpful in conjunction with psychotherapy, particularly for patients with major depression and for patients with prominent neurovegetative signs of depression. A tailored, individualized approach that considers the patient's unique needs can strengthen the therapeutic relationship, which may be the primary "nonspecific factor" through which all psychotherapies appear to benefit patients. PMID- 1600486 TI - Outcomes of geriatric depression. AB - Improvement in the methodology of longitudinal investigations and increasing research interest in depressive disorders led to findings of clinical and heuristic importance. Outcomes, such as chronicity of depression, relapse, recurrence, and development of dementia, appear to be predicted by different clinical and laboratory findings. Chronicity of depression may be predicted by long duration of the current or previous episodes, coexisting medical illness, high severity of depression, nonmelancholic presentation, delusions, and perhaps cognitive impairment and neuroradiologic abnormalities. Predictors of relapse and recurrence of geriatric depression include multiple previous depressive episodes, high severity of illness, "double depression," presence of "exit" events, and intercurrent medical illnesses. Development of dementia may be predicted by a transient dementia syndrome during a depressive episode ("pseudodementia"), onset of the first depressive episode in the senium, and neuroradiologic abnormalities such as cortical atrophy and rapidly evolving ventricular enlargement. Long-term antidepressant treatment, if not controlled by a research protocol, usually is of low intensity and has a questionable effect on the outcome of depression over a long period of time. For this reason, naturalistic treatment studies are useful for identifying subgroups of depressives and time periods of high risk for specific adverse outcomes. This knowledge is particularly important in frail elderly populations who are vulnerable to side effects of antidepressant treatments. The next step is to conduct controlled-treatment studies and examine the capability of antidepressant treatments to prevent adverse outcomes in the high-risk populations identified through naturalistic treatment studies. Controlled-treatment studies can provide findings that clinicians can use to assess the risk-benefit ratio of continuation and maintenance treatments of geriatric depression. The heuristic importance of knowing the outcome of geriatric depression is that it permits identification of clinically and, to some extent, biologically-homogeneous groups. Given the absence of specific and sensitive laboratory tests, outcome is perhaps the "next best thing" to brain autopsy for subclassifying geriatric depression. Biologic measures of structural and functional abnormalities can then be used in homogeneous subgroups for the pursuit of pathophysiologic or etiologic studies. PMID- 1600487 TI - The impact of depression on quality of life of the elderly. AB - The individual who suffers the onset of a clinical level of depression is likely to experience a substantial transformation of the quality of his or her whole life. This can be demonstrated by examining the patterns of the course of depression from its onset to the end of life, in particular the impact of depression on morbidity (including symptom distress), functioning, and mortality. PMID- 1600488 TI - Geriatric mania. AB - Some general themes emerge from available information concerning manic states and bipolar disorders in late life: heterogeneity of both clinical features of the manic episode and of antecedent illness course; late average age at illness onset; lower rate of affective illness in families of late-onset cases; association of medical and neurologic illness and drug treatments with late-onset cases; utility of lithium salts for acute, continuation, and maintenance treatment; changes in lithium pharmacokinetics associated with aging, disease, and drugs resulting in increased plasma concentration/dose ratios. Geriatric manic states and bipolar disorders present opportunities for research. Investigation may illuminate the nature of mood disorders across the age spectrum, lead to better diagnosis and management in the elderly, and suggest strategies for prevention based on insights into pathophysiologic and pathogenetic mechanisms. Strategies that can be pursued include: longitudinal studies to evaluate differences in affective, cognitive, and other outcomes in geriatric patients with late-onset compared with early-onset illness; studies of psychopathology, family history, and illness course in organic mood disorder, manic; retrospective categorization when cognitive impairment accompanies acute episodes; studies of mania occurring in the context of dementing illness; application of neuroimaging and other laboratory measures to geriatric manic states; contrast of clinical and laboratory findings in early-onset geriatric patients and young adult patients to assess effect of age; definition of lithium concentration-effect relationships in regard to efficacy and toxicity in patients with and without cognitive impairment/dementia. PMID- 1600489 TI - Anxiety disorders and their treatment. AB - Anxiety disorders appear to be among the most common psychiatric illnesses of the elderly. Although systematic studies of the phenomenology and treatment of anxiety disorders in the elderly are rather scant, inferences based on studies of younger patients combined with careful clinical observations can be very helpful for both diagnostic and treatment purposes. Several medical conditions can mimic anxiety disorders and suggest a need to consider a possible underlying organic condition during the process of evaluation. Clinical evaluation should be complemented by rating scales and laboratory tests where appropriate. Anxiety disorders occurring for the first time in late life appear to be milder in symptomatology than early-onset disorders. Most anxiety disorders can be well managed using the available treatments. It appears that short-acting benzodiazepines, such as oxazepam and lorazepam, are the treatment of choice for short-term symptoms of geriatric anxiety. For anxiety of longer durations (e.g., greater than 6 months), a nonbenzodiazepine such as buspirone seems preferable. Antidepressants seem effective in cases of mixed anxiety-depression or panic disorder. There is clearly a need, however, to perform more controlled clinical trials of these medications to establish empirically derived guidelines for safety, efficacy, and specificity of these drugs for the elderly population. Finally, nonpharmacologic methods such as cognitive-behavioral treatments can be very effective for the management of certain anxiety disorders, particularly phobias. PMID- 1600490 TI - Sleep disorders in geriatric patients. AB - The elderly have more organic sleep problems disturbing sleep and contributing to insomnia than younger individuals. The most common disorders afflicting the elderly are obstructive sleep apnea, restless legs syndrome, and nocturnal myoclonus. Poor sleep habits often aggravate or contribute to the ongoing difficulty with sleeping. In the depressed elderly, characteristic EEG changes occur that may help distinguish major depression from pseudodementia; however, it should be considered that pseudodementia may be a harbinger of primary dementia. A careful sleep history and often evaluation by polysomnography are central to the management of sleep problems in the elderly. In conjunction with treatment of any underlying organic sleep disorders, brief administration of short-acting benzodiazepine sedatives for sleep onset insomnia or rapid-acting intermediate half-life benzodiazepines for sleep maintenance insomnia can be quite helpful in the elderly, especially if behavioral techniques also are employed. Elimination of medications, alcohol, and caffeine, which disturb sleep, is also an important part of the treatment approach. PMID- 1600491 TI - Management of localized prostate cancer. AB - BACKGROUND: Given the variable natural history of prostate cancer, prognostic parameters are needed to help guide treatment decisions in individual patients. In some series, analysis of DNA ploidy has correlated well with prognosis. This review was performed to determine whether flow cytometry could be used to help guide treatment decisions in patients with localized carcinoma of the prostate. METHODS: Two hundred consecutive patients were observed for a minimum of 10 years after radical prostatectomy. Follow-up information was incomplete in 14 patients, leaving 186 for analysis. Clinically, there were 72% Stage B tumors and 28% Stage A. RESULTS: Sixty percent of patients were alive with a minimum of 10 years of follow-up, and 47% apparently were tumor free. Twenty-two percent died of carcinoma of the prostate and 18% of other causes. The median time until death from prostate cancer was 6.5 years. Seventy-four percent of tumors were diploid on flow cytometry. Fifty-three percent of patients with diploid tumors survived 10 years without recurrence, whereas 20% died of carcinoma of the prostate. Aneuploid tumors were identified in 16% of the total group; 47% of these patients were alive at 10 years, whereas 24% had died of prostate cancer. CONCLUSIONS: Aneuploid tumors have a worse overall prognosis than diploid lesions. However, the correlation is not strong enough to allow treatment decisions on an individual patient basis. Analysis of DNA ploidy was no more accurate than Gleason histologic grading. PMID- 1600492 TI - Prospective, conservative management of localized prostate cancer. AB - BACKGROUND: Currently, no randomized trials of the various treatment options for localized prostate cancer have been reported. Therefore, radical prostatectomy and external irradiation are offered as the primary management options and are thought by many to be curative. METHODS: All patients in this series with a confirmed diagnosis of cancer of the prostate, localized, were given the option of expectant management in addition to the popular ones. Therefore, 233 patients with localized Stage A and B cancer were observed prospectively and conservatively for a period of 22 years, with a management plan of watchful waiting for most patients until signs and/or symptoms of disease activity occurred. In 44 patients interstitial I-125 irradiation implantation and pelvic lymphadenectomy were performed in those who received surgical intervention. RESULTS: No patient received external irradiation or radical prostatectomy in this series. The overall survival of patients was not statistically different from the United States life-tables probability for men of similar ages when the study ended for reporting purposes in June 1989. Exclusive of the 6 patients lost to follow-up, 52 patients survived less than 3 years, whereas 181 patients have survived more than 3 years. CONCLUSIONS: Because of the favorable results in this expectant management study, it appears prudent that all patients with localized prostate cancer should have this management option as well as radical surgery or external irradiation. PMID- 1600493 TI - Stage D1 prostate cancer treated by radical prostatectomy and adjuvant hormonal treatment. Evidence for favorable survival in patients with DNA diploid tumors. AB - BACKGROUND: Stage D1 disease is found in at least every sixth patient undergoing bilateral pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer (PC). Previous recommendations for monotherapy using surgery, radiation, or systemic therapy alone for Stage D1 disease have usually been associated with a poor outcome in regard to progression and survival. Unlike other pathologic stages, D1 disease treated with RRP is mainly related to DNA ploidy pattern in regard to all end points (progression and survival) and immediate adjuvant hormonal treatment (AHT) rather than to the usual pathologic variables, including the number of positive nodes. METHODS: Complete DNA ploidy information was available in 370 patients with Stage D1 disease (age range, 40-77 years; mean, 64 years) undergoing RRP with or without AHT with a follow-up of up to 22 years (mean, 5 years). RESULTS: Overall, 80% of all DNA ploidy classes (diploid, 37%; tetraploid, 46%; and aneuploid, 17%) had AHT that highly significantly delayed progression for diploid (P less than 0.0001) more than tetraploid (P less than 0.0001) and more than aneuploid (P less than 0.0001) tumors. Significant prolongation of the disease-free interval might have improved the quality of life for tetraploid and aneuploid patients. Survival (crude and cause-specific) was significantly (P = 0.02) improved only for diploid patients who received AHT but not for tetraploid and aneuploid patients. This was due to the significantly accelerated death rate after progression in those patients with early AHT for tetraploid and aneuploid (but not diploid) tumors. Delayed (on progression only) AHT resulted in high progression rates for all DNA ploidy classes (aneuploid greater than tetraploid greater than diploid); e.g., 21 of 30 diploid patients progressed and 6 patients died from disease at a median of 31.5 months in spite of immediate hormone treatment on progression. RRP and AHT for patients with Stage D1 disease resulted in a highly significant delay in overall progression (76% at 10 years) and excellent local control, depending on DNA ploidy pattern (diploid greater than tetraploid greater than aneuploid) compared with a treatment regimen without AHT (24% overall nonprogression); only 20% of all patients with AHT are projected to die of disease at 10 years. Disease in diploid patients (37%) treated with AHT rarely progressed and those patients are unlikely to die of disease in 10 years or less; delayed (on progression) hormone treatment for diploid patients seemed ineffective. Inclusion of values for prostate specific antigen led to a higher failure rate on progression, and this is dependent on DNA ploidy class (diploid greater than tetraploid greater than aneuploid). CONCLUSION: Only patients with nondiploid tumors should be entered into prospective studies using innovative adjuvant treatment protocols to improve survival. PMID- 1600495 TI - Locoregional disease. PMID- 1600494 TI - Controversies in the treatment of metastatic prostate cancer. AB - BACKGROUND: Prostate cancer is the most common cancer in American men today. Unfortunately, at the time of diagnosis, most men will have either regional or distant metastatic disease. METHODS: Six hundred three patients with advanced prostate cancer who could be examined were randomized in a double-blind, placebo controlled trial to receive the luteinizing hormone-releasing hormone (LHRH) agonist leuprolide with either flutamide or placebo. RESULTS: Patients receiving the combined therapy arm of leuprolide and flutamide had an increased progression free survival time of 16.9 versus 13.8 months and a survival advantage of 35.1 versus 20.3 months. A more striking difference was found in the subset of patients receiving combination therapy who had good performance and minimal disease. CONCLUSIONS: There appears to be a definite advantage of combination therapy over leuprolide alone, especially in patients with minimal disease and good performance. Another larger intergroup study using orchiectomy and flutamide versus orchiectomy and placebo is currently underway. PMID- 1600497 TI - College-university collaboration. PMID- 1600496 TI - Distant disease. PMID- 1600498 TI - Measuring a child's pain. PMID- 1600499 TI - Pain and the chemically dependent patient. PMID- 1600500 TI - Pain management: know the facts. PMID- 1600501 TI - Fun & games. PMID- 1600502 TI - Fetal tissue transplants. PMID- 1600503 TI - Indwelling catheters: problems and management. PMID- 1600504 TI - [The nursing process according to Orem. A concrete very simple example explains how to follow this nursing process]. AB - The author shows how Orem's theory, based on self care, can be applied to the nursing care of a patient with severe cardiac illness. To do so, she explains in detail what is looked for in the patient's history to delineate problems, and then uses a systematic care plan approach to solve them. In the patient's history, the nurse looks for information on each need, and on the specific factors in the patient's life and health history that will have an impact on the patient's capacity to meet Orem's goal of self care. Inabilities are labelled self care deficits. When the self-care deficit is well understood, it is important then to determine the source of the patient's difficulty. Orem states that there are two main phases to self-care: the decision and the action. The author illustrates this through a discussion of the patient's difficulty to stop smoking. She then explains a particular method to write a nursing diagnosis that directs the nurse to work, not on the deficit itself, i.e. in this case smoking, but rather on the patient's lack of knowledge. The "SMART" approach to writing nursing care objectives (specific to the patient and the current situation, measurable, attainable by the client in a reasonable period of time, realistic for the current situation, and truthful or having clear significance for the patient at the moment) is detailed along with interventions that respect Orem's concept of nurse-patient contracts. The nursing process based on Orem's conceptual framework is not difficult to manage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600505 TI - [The anti-depressive effects of post-infarct exercises]. AB - Twenty-nine per cent of patients hospitalized following their first myocardial infarction (MI) are depressed. This percentage decreases with time to 15 per cent at six weeks, and fluctuates between 10 and 13 per cent at three and six months post-MI, respectively. This literature review indicates that exercise training programs are not the treatment of choice to reduce severe post-MI depression. However, in moderately depressed MI patients, their sense of humor is improved, especially if the exercise component involves some degree of socialization and counselling. The lack of significant findings may be compounded by other factors such as incorporating other life-style modifications, the patients' expectations and self-efficacy, and the type of measurement utilized to detect changes in depression levels over time. The type of depression scale used in most studies, the Minnesota Multiphasic Personality Inventory (MMPI), may also be incorrect for MI patients, since the etiology of post-MI depression varies from minor depression to a major depressive episode. The MMPI was developed for use with persons with psychiatric illness. Post-MI depression is considered a normal "uncomplicated bereavement" for the majority of patients. The optimal method used to identify post-MI depression following hospitalization seems to be observation and interview. This is essential to pinpoint the symptoms characteristic of uncomplicated bereavement. PMID- 1600506 TI - Cell migration influences collagen gel contraction. AB - Collagen gel contraction is a striking feature where the presence of serum factors seems to be critical. However, the mechanism by which these factors control the contraction process is poorly understood. Therefore, the purpose of these studies was to examine by dynamic and morphological approaches, the influence of serum factors on fibroblast-mediated collagen gel contraction. Cellular behavior was assessed in terms of cell migration which was related to the effectiveness of the contraction process. Media containing serum, fibronectin depleted serum, and a synthetic culture medium were employed to modulate cellular organization in the three-dimensional gel. The data suggested that the gel contraction process is controlled by cell-matrix and cell-cell interactions. The absence of plasma fibronectin in culture medium allowed faster cell adhesion and spreading on collagen fibrils, but did not influence the contraction rate. Serum factors, other than fibronectin, led to a less extensive gel contraction due to the impairment of cell migration. Therefore, cell migration seems to be an important factor by which the effectiveness of gel contraction is controlled. PMID- 1600507 TI - Localization by immunogold labelling of HIV-1 structural proteins on Lowicryl embedded HIV-1 infected cell ultrathin sections. AB - Using several HIV-1-specific antibodies and the immunogold labelling technique, we have detected and localized distinct viral proteins on ultrathin sections of HIV-1 infected cells embedded in the Lowicryl K4M resin. Monoclonal antibodies (MAbs) against p24, p17 and gp160/gp41 showed a preferential labelling on viral formations still attached to the cell membrane (budding process) or free in the extracellular space. The anti-p24 and the anti-p17 MAb yielded a gold labelling not only on mature but also on immature virions where the gold particles were associated with the ring-like electron-dense material. The three HIV-1-specific antibodies against p24, p17 and p55 yielded a cross-reaction with HIV-2 in agreement with the conservation of the internal antigenic determinants of both viruses. In all instances, there was no specific immunogold labelling over the cells, suggesting that once the virus structural proteins were synthesized, they were promptly utilized for virus assembly at the plasma membrane level. PMID- 1600508 TI - Degrading and non-degrading pathways in fluid-phase (non-adsorptive) endocytosis in human blood platelets. AB - A morphological study of the endocytic pathways in non-activated human blood platelets has been made using fibrinogen-stabilized colloidal gold as a fluid phase marker, and acid phosphatase as a marker for lysosomes. Two pathways of constitutive endocytosis were demonstrated: one pathway was mediated by clathrin coated vesicles which formed at the platelet surface and the surface-connected, canalicular membrane system and which fuse with and deliver their contents to the platelets' secretory alpha-granules. The other pathway follows a degrading, endosomal-lysosomal route and appears to be clathrin independent. Endosomes containing marker particles originate from the surface-connected canalicular system, through which ambient fluid percolates. An account is given of the pleomorphism of platelet lysosomes, and evidence is presented for a lysosomal, focal autophagia in platelets which may be linked to platelet senescence. Lysosomes in non-activated platelets are thus involved in the same processes as lysosomes in other cells. PMID- 1600509 TI - Immunoelectron microscopical evidence of a calcium receptor function in parathyroid, placenta and kidney. AB - The parathyroid, kidney and placenta have been investigated for ultrastructural signs of immunostaining with a murine monoclonal IgG 1-antibody denoted E11. Dispersed cells and tissue sections revealed a finely granular, electron dense precipitate after fixation with periodate-lysine-paraformaldehyde and indirect immunoperoxidase staining with the native or biotinylated antibody. This precipitate was confined to the surface membrane of parathyroid chief cells of normal and adenomatous human glands as well as the bovine and rat parathyroid parenchyma, preferentially the brush border membrane of proximal tubular cells in the human, rat and mouse kidney, cytotrophoblast cells of the human placenta, and trophoblast cells lining fetal blood vessels in the rat placenta. Since the E11 antibody recognizes a large glycoprotein regulating intracellular calcium mobilization and cation fluxes across the cell membrane, the present findings suggest the existence of a similar calcium receptor function on cells involved in different aspects of the calcium homeostasis within a variety of species. PMID- 1600510 TI - Action of propranolol on the atrial cardiomyocytes of rats submitted to cold stress. AB - Subcellular changes of the atrial cardiomyocytes of rats caused by cold showed a) altered mitochondria with edema and lysis of crests; b) myofibrils with marked heterogeneity of patterns and ruptures, c) myofilaments disarrangement, partial necrosis and disintegration of filaments, d) lesser concentration of atrial granules in the perinuclear area. Atrial muscle fibers of propranolol-treated rats previously stressed by cold showed a marked decrease of the morphological alterations observed in the animals submitted to cold stress without propranolol protection. PMID- 1600511 TI - Rat hepatic lipocytes express smooth muscle actin upon activation in vivo and in culture. AB - Myofibroblasts are mesenchymal cells that are prominent in liver injury. The origin of myofibroblasts in liver is debated, although morphologic evidence to date has suggested that these cells are derived from lipocytes (fat-storing cells, Ito cells). In the present study, we have utilized smooth muscle alpha actin antibody--a marker of myofibroblasts and smooth muscle cells--to study lipocytes in situ in normal and fibrotic rat liver as well as during their 'activation' in culture. Dual immunofluorescence studies on tissue sections from normal liver identified lipocytes as perisinusoidal desmin-positive, smooth muscle alpha actin-negative cells. In bile duct obstructed fibrotic liver, desmin positive cells were numerous in areas of fibrosis and these cells also exhibited smooth muscle alpha actin. In carbon tetrachloride-induced fibrosis, cells expressing both desmin and smooth muscle alpha actin were present in fibrotic bands and in regenerating nodules. These results suggested that lipocytes had acquired characteristics of myofibroblasts during liver injury. To further address this issue we examined lipocytes immediately after isolation and also in primary culture. In freshly isolated lipocytes from normal liver, smooth muscle alpha actin was absent. In contrast, freshly isolated lipocytes from CCl4-treated animals expressed this smooth muscle marker immediately after isolation. In primary culture on plastic, lipocytes from normal liver began to express smooth muscle alpha actin coincident with culture-induced activation; at 14 days, smooth muscle alpha actin was identified in all cells. Electron microscopy demonstrated a highly developed array of microfilament bundles characteristic of actin filaments. Immunoblot of culture-activated lipocytes using the smooth muscle alpha actin antibody demonstrated the expected 42 kD protein (corresponding to the molecular size of smooth muscle alpha actin). Although smooth muscle alpha actin was readily detectable in culture-activated cells, it was not expressed in cells in which a quiescent phenotype was preserved by maintenance in culture on a laminin-rich gel. These findings demonstrate that the acquisition by lipocytes of a smooth muscle marker accompanies their 'activation', and are consistent with the hypothesis that lipocytes transform to myofibroblasts during liver injury. PMID- 1600512 TI - A correlative SEM/TEM examination of the endothelium surface in neural capillaries. AB - The modifications of the endothelial surfaces were analyzed in growing neural microvessels by scanning and transmission electron microscopes in the optic tecta of chick embryos and chickens. The endothelial inner aspect appears regular and smooth in the early stages of the vessel growth (7th incubation day). Later (14th incubation day) both the abluminal and luminal surfaces of the endothelium follow a very sinuous course and the luminal ones appear extremely rich in pleomorphic microprojections. When the endothelium differentiation is concluded (5-day-old chicken), the cells are very thin and again exhibit regular and smooth surfaces. These findings reveal a great mobility of the cell membrane of the endothelial cells when they are growing longer and thinner by a moulding process. Moreover, the presence of a number of pinocytotic pits in the embryo vessels would indicate that the neutral vessels, provided with a typically low pinocytotic activity in the adult life, are engaged in this function during development. PMID- 1600513 TI - Effects of chronic and in utero treatment with diuretics on mouse exocrine cells studied by X-ray microanalysis. AB - In an attempt to develop an animal model for the disease cystic fibrosis, mice were chronically treated with diuretics. In addition, pregnant mice were treated with diuretics and the effect of this treatment in utero on the newborn mice was studied. Pancreas and submandibular gland acinar cells were investigated by X-ray microanalysis and transmission electron microscopy. Long-term treatment with furosemide (up to 13 months) caused transient changes in the elemental content of the pancreatic acinar cells: a decrease in chloride and sulfur, and an increase in phosphorus, potassium and magnesium. All changes normalized with prolonged treatment. Some morphological changes were found in the zymogen granules. Treatment with amiloride or furosemide in utero caused a decrease in cellular sodium and chloride levels, indicative of inhibition of transepithelial ion and fluid transport. Also treatment of adult animals for two months with amiloride caused lower intracellular sodium and chloride levels. In adult animals only minor effects of diuretic treatment on submandibular gland acinar cells were noted. In utero treatment with amiloride caused an increase in sodium and chloride content indicative of cell damage. PMID- 1600514 TI - Supraependymal cell clusters and invaginations in the epithalamic third ventricle of the rabbit (Oryctolagus cuniculus). AB - Supraependymal cell clusters and deep invaginations of the ependymal wall, situated in the epithalamic area of the third ventricle of the rabbit have been precisely located by means of semithin serial sections. A study of these structures has been carried out using optical transmission and scanning electron microscopy. The round shaped supraependymal cell clusters revealed two types of cells: type I, of central location and bearing the morphological features of neurons and type II, located peripherically and of possible ependymary origin and nature. In the same epithalamic region, deep invaginations of the ventricular wall, lined by ependymal cells of similar morphology to those coating the rest of the third ventricle, are described. The functional role of both structures is discussed. PMID- 1600515 TI - Reversible intracellular displacement of the cytoskeletal protein and organelles by ultracentrifugation of the sympathetic ganglion. AB - Superior cervical ganglia of rats were centrifuged at 40,000 rpm (160,500 g) for 1 h at 4 degrees C. Most neuronal somata exhibit a minor centripetal domain free of organelles and a major centrifugal domain rich in organelles. The former is occupied by numerous fine granules having low electron density unlike ribosomes in epoxy sections stained with uranium and lead, and is occupied by a meshwork of microtrabecular or filamentous elements similar to that of the centrifugal domain as well as that of the normal cells in PEG (polyethylene glycol)-processed embedment-free sections without staining. The latter centrifugal domain contains regular cell organelles except for neurofilaments without stratification. All the organelles are suspended in the meshwork of microtrabecular or filamentous elements. In immunolight microscopy, NFPs (neurofilament proteins) are confined to the centripetal domain. In immunoelectron microscopy using ultrathin cryosections and the protein A-gold labeling, numerous gold-particles for NFPs were deposited randomly in the centripetal cytoplasmic domain without long linear alignment. In the PEG sections the gold-labelings for NFPs are randomly deposited on portions of the microtrabecular strands in the centripetal domain. After incubation of the centrifuged ganglia in the anterior eye chamber overnight, NFPs immunoreactivity appears again diffusely throughout the entire cytoplasm of all neuronal somata in immunolight microscopy. The organelle-free domain of the cytoplasm is no longer visible in electron microscopy. The present findings are discussed in relation to the state of the cytoplasmic soluble proteins and the reality of the microtrabecular or filamentous elements in the cytoplasm. PMID- 1600516 TI - Acute renal injury by tetraethyl orthosilicate in mice: ultrastructure, histochemistry and X-ray microanalysis. AB - Tetraethyl orthosilicate (Si(OC2H5)4, or TEOS) is a silicon-containing compound which has widespread industrial applications and which has been documented as biohazardous. The histopathological features and mechanism of TEOS toxicity in the kidney of ICR mice were investigated in a light and electron microscopy study, which included energy dispersive X-ray microanalysis. TEOS was given to mice as intraperitoneal injection of approximately 1,670 mg/kg body weight in experiments based on a 24 h time-scale. Tissues were examined after sampling either immediately on death if this occurred within 24 h or, in the case of surviving animals, after sacrifice at 24 h. Renal injury was considered to be the most probable cause of death, on the basis of the following main findings: 1) acute tubular necrosis (glomerular lesions were absent); 2) a dense deposit of silicon over the microvilli of dead tubular epithelial cells; 3) an abundant aggregation of hydroxyapatite crystals containing calcium in the cytoplasm and mitochondria of the dead tubular epithelial cells; and 4) abundant myelinosomes and some hydroxyapatite crystals in the cytoplasm of viable proximal convoluted tubule epithelial cells. It was speculated that silicon compounds may bind to the plasma membranes of the proximal convoluted tubule epithelial cell microvilli and damage or interfere with membrane calcium channels. The resulting calcium ion imbalance may play a role in the subsequent progression of acute tubular necrosis by TEOS. PMID- 1600517 TI - Copper deficiency and pigmentation in the rat: morphofunctional aspects. AB - The effects of a low copper diet on pigmentation, pigment cell and melanosome morphology have been investigated in ACI/T male rats. After a three months treatment the fur and skin pigmentation is reduced as compared to the controls. The melanocytes of the treated rats show the phenotype of active pigment cells while some melanosomes are abnormally differentiated: both lamellar and granular organelles are present in the same pigment cell and mosaic age melanosomes appear. The abnormal melanosome structure expressed by the treated-rat melanocytes is also evident in vitro. After incubation with deoxycholate the melanosomes from the low-copper diet treated rats are much more altered than those from the control rats. The phenotype of the rats starved for copper seems to mimic as regards pigmentation the phenotype of the mouse Mo (mottled) mutation that is an experimental model of the Menkes' kinky hair syndrome. In conclusion copper deficiency seems to affect both the morphology and function of the pigment cells. PMID- 1600518 TI - The microvessels in hypertrophic scars, keloids and related lesions: a review. AB - The healing of a deep surface wound in humans begins with the formation of granulation tissue and includes a marked microvascular regeneration, initially in an inflammatory milieu. The inevitable sequel is usually a hypertrophic scar or keloid in which there is significant microvascular occlusion. The occlusion begins in the granulation tissue and is the result of an excess of endothelial cells. Several other examples of fibroses contain significant microvascular occlusion. The evidence demonstrates that hypertrophic scars and keloids are hypoxic, undoubtedly due to the microvascular occlusion. Hypoxia may stimulate excessive production of collagen, which forms the bulk of these lesions, from fibroblasts and myofibroblasts. The origin of the new fibroblast remains undetermined. The current evidence suggests it is probably not the pericyte. Resident or peripheral fibroblasts, endothelial cells or undifferentiated cells from the growing tips of microvessels are possibilities. Differential degeneration, or apoptosis, of the fibroblasts, pericytes and microvessels occurs from granulation tissue through hypertrophic scarring. Compartmentalization of fibroblasts between lateral microvascular branches probably accounts for nodule formation. Differential degeneration of the lateral microvessels may account for increases in collagen nodule growth and ultimate size. Hypertrophic scars and keloids may be resolved through light topical pressure maintained over time. Under such treatment, fibroblasts, pericytes and endothelial cells degenerate, probably at a rate greater than that which occurs normally. As degeneration or apoptosis continues the nodules and scar become more avascular and more hypoxic, prompting fibroblast death and release of lysosomal enzymes important for maturation. An alternative treatment, particularly of the granulations, would be to control excessive endothelial (microvascular) or fibroblast proliferation or collagen synthesis. To this end, determination of endothelial or fibroblast cell phenotype for possible antibody targeting may be mandatory. PMID- 1600519 TI - Improved "electrophoretic map" of breast cyst fluid proteins. AB - Human breast cyst fluid (BCF) proteins were evaluated by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) after protein denaturation in the presence or absence of 2-mercaptoethanol. Both electrophoretic techniques yielded characteristic and reproducible banding patterns and achieved a high degree of resolution. The known four major protein bands were identified; silver-staining procedure resulted in more discrete bands (at least 13). Crossed immunoelectrophoresis analyses of BCF allowed an improved protein mapping of this pathological fluid, presenting the opportunity of simultaneous quantification and identification of at least 22 proteins. The clinical and biological potential of these electrophoretic methods for detecting BCF proteins is discussed. PMID- 1600520 TI - Presence of epidermal growth factor receptor in breast smears of cyst fluids: relationship to electrolyte ratios and pH concentration. AB - The purpose of this study was to evaluate and correlate different high risk factors in breast cysts to produce a more accurate prognosis. We considered the cytology of the lining epithelium (apocrine or flattened), the Na+/K+ ratio (less than 3; greater than or equal to 3), the pH (lower, equal, or higher than 7.30), and the EGFr (present or not) in an attempt to reach better prognoses and diagnoses by evaluating more than one risk factor. Our material of 40 macrocysts consisted of 23 simple cysts with flattened epithelium and 17 complex cysts with apocrine or hyperplastic epithelium. In the simple cysts, the Na+/K+ ratio was greater than or equal to 3, while in the complex cysts the Na+/K+ ratio was, in all cases but one, less than 3. The pH was not significantly lower than neutral in the complex cysts. The EGFr was detected in 5 of 23 simple cysts and in 12 of 17 complex cysts. In conclusion, reaction of EGFr in smears of cyst fluids with the low intracystic electrolyte ratios may provide an explanation of why women with apocrine metaplasia or epithelial hyperplasia may be at higher risk of breast cancer than women with cysts which are lined by flattened epithelium. PMID- 1600521 TI - Epidemiologic evidence for the role of indoor tobacco smoke as an initiator of human breast carcinogenesis. AB - Earlier research suggested an appreciable latent period between the time of exposure to indoor tobacco smoke and the detection of breast cancer. A close relationship was found in the U.S. between state breast cancer mortality from 1978 through 1981 and state cigarette sales from 1950 through 1954 (R = 0.64, p less than 0.001). The correlation declined for sales in subsequent years but remained highly significant until 1970, but not thereafter. Thus, it appears that the role of indoor tobacco smoke in breast carcinogenesis is that of an initiator and/or an early-stage promoter in the process that leads after 15 to 30+ years to cancer. Trends in cigarette consumption from 1915 to 1965 paralleled breast cancer incidence in Connecticut women from 1935 to 1989. The 1953 and 1975 peaks in incidence were related to 1930 and 1953 peaks in cigarette consumption, respectively, showing a 22.5-year latent period. The drop in cigarette sales in the mid-1950s was followed by a surge to new highs in sales in the early 1960s in the great majority of the states. Approximately 23 years later, breast cancer incidence rates in the mid-1980s in all nine SEER populations are reflecting that surge in cigarette sales, rising to an all-time high in 1985. The earliest declines in breast cancer incidence should occur in New York and Connecticut, where cigarette sales have fallen most dramatically. By the year 2015, white women in the South, currently living with the men with the highest lung cancer rates in the U.S., are expected to show the highest breast cancer rates in the country. PMID- 1600522 TI - Maternal smoking and irradiation during pregnancy as risk factors for child leukemia. AB - The effect of joint exposure to diagnostic X-rays and maternal smoking during pregnancy was compared in a case-control study of 216 children with cancer (128 cases with acute lymphoblastic leukemia [ALL] and 88 with solid tumors) and 301 control children with insulin-dependent diabetes mellitus (IDDM). Exposure to diagnostic X-rays combined with smoking of ten or more cigarettes per day gave a relative risk of 3.6 (95% CI, 1.8 to 7.0) and a positive dose response relation for ALL in the offspring (p less than 0.001). When examined alone, X-rays gave a relative risk of 1.8 (95% CI, 1.1 to 3.1), and smoking a relative risk of 2.2 (95% CI, 1.1 to 4.5). No similar trend was seen for solid tumors. Potential confounding was examined after stratification on maternal smoking-diagnostic X ray exposure and each of potential confounders, but there was little change in the risk ratio. We conclude that the risk of ALL in the offspring was more than threefold higher when smoking was combined with diagnostic X-ray during pregnancy. PMID- 1600523 TI - Hepatectomy accelerates the growth of transplanted liver tumor in mice. AB - To study the effect of hepatectomy on the growth of liver tumor, Shionogi Carcinoma 42, a mammary tumor, was transplanted into the liver of mice which had undergone 40% hepatectomy. The liver tumor and the number of pulmonary metastases in hepatectomized mice were significantly larger than those in nonhepatectomized mice. Responses to lectins and IL-2, subpopulations, and cytotoxicity to YAC-1 and P815 cells of splenocytes were assessed to evaluate immunological status. At the initial phase after hepatectomy and tumor transplantation into the remaining liver, NK activity transiently increased, and function of B and T cells, especially of helper T cells, decreased, while B-cell function recovered beyond normal levels in a later phase. These results suggest that liver may play an important immunological role and that the immunological modification after hepatectomy may be responsible for the accelerated growth of liver tumor. Accordingly, some adjuvant immunotherapy may be recommended for the prevention of recurrence after hepatectomy for liver tumor. PMID- 1600524 TI - Immunologic findings in tissue of thyroid carcinoma. AB - We studied the occurrence of DR-antigen (DR-Ag) positive thyroid epithelial cells (TEC), lymphocyte (Ly)-subsets, and antigen-presenting cells (APC) in thyroid carcinoma and the influence of thyroid-stimulating hormone (TSH) on immunologic behavior. Tissue slices from various thyroid carcinomas (n = 14) and endemic goiters (n = 12) were investigated by immunohistochemical methods (PAP/APAAP/FITC) using monoclonal antibodies (MoAbs) against DR-Ag, dendritic cells (APC), endothelial cells, CD-3 Ly, CD-4 Ly, and CD-8 Ly. Monolayers of TEC were cultured in the presence or absence of TSH (0.01 mU/ml) and/or PHA (0.1 mg/ml) over 24 h and screened for DR-Ag expression. Various ranges of DR-Ag expression were detectable in 13 thyroid carcinomas. One thyroid carcinoma and all endemic goiters were DR-Ag-. The amount of APC and local infiltrating Ly correlated very well with the presence and intensity of DR-Ag+ TEC. The lymphocytic CD-4/CD-8 ratio varied in a wide range. No prevalence of Ly distribution for any type of carcinoma was found. PHA induced DR-Ag expression in all thyroid carcinomas and endemic goiters. This effect was enhanced significantly by TSH. DR-Ag expression on thyroid carcinoma cells may be considered as an immune activating factor. These "neoantigens" may be induced by lymphokines released by the local immune competent cells. The distribution of Ly and DR-Ag+ TEC in thyroid carcinoma seems to represent the individual immunologic response against the tumor. Whether TSH acts as an immune modulator directly or indirectly, as described elsewhere, cannot be concluded from these results. PMID- 1600525 TI - Cytological analysis of benign breast disease. AB - The different histological lesions of benign breast disease (BBD) are the result of interactions and regional prevalence of epithelial, myoepithelial, apocrine, and "null" (undifferentiated) cell types. We conducted an immunocytochemical analysis on 14 cases of BBD. Specific markers were employed to identify the different cell types; proliferation in these cells was revealed either by bromo deoxyuridine uptake or PCNA ("cyclin") localization. The results indicate that apocrine cells do not undergo proliferation, representing therefore a terminally differentiated cell. The question related to the preneoplastic potential of BBD and on which cell type might possibly represent the precursor of in situ cancerous lesions remains unanswered. However, our data tend to exclude that such a putative proliferating precursor might be represented by apocrine or myoepithelial cells or even by the epithelial cells featuring epitheliosis. PMID- 1600526 TI - Benign breast disease: indicators of increased breast cancer risk. AB - Assessment of cancer risk, particularly with a view toward targeting strategies for prevention, is a recent development. The future will see the garnering of more specific information about determinants of risk and their interaction with screening prevention and therapeutic modalities. We are not a full professional generation removed from a time when the question of malignancy in the breast was absolute, yes or no. Now special types of breast cancer are recognized that pose little threat to life, while some benign conditions indicate greatly increased risk of death from cancer. Comparisons of premalignant determinants in other organ systems indicate that cytologic, histologic, and metaplastic features may be more or less important in different organs. Their separate and combined analysis as predictors give a complex measure of tissue organization, which is often predictive of concurrent cancer and/or future cancer development. In proliferative breast disease, the markers of cancer risk may be classified into histologic categories of slightly, moderately, and markedly increased risk. In cases of slightly increased risk, the probability for cancer development is 1.5 to 2 times that of the general population; a moderately increased risk denotes that the likelihood of cancer development may be 4 to 5 times greater; a markedly increased risk has a predictive value of 9 to 10 times that of the general population. PMID- 1600527 TI - Using biological measurements, can patients with benign breast disease who are at high risk for breast cancer be identified? AB - In order to address the question of whether biological measurements might identify women with benign breast disease (BBD) at particular risk for breast cancer, analyses were performed on cyst fluids aspirated from patients presenting with palpable breast cysts. Electrolyte profiles showed that cyst fluids may be divided into major subpopulations which differ in terms of histological appearance of cyst lining epithelium, pattern of cyst presentation, and levels of other fluid constituents such as androgen conjugates and epidermal growth factor. Analysis of cyst fluids from 18 patients who subsequently developed breast cancer 1 to 8 years later showed that 12 individuals had group A cysts, three had group B cysts, and three presented with a mixture of the two types. Therefore, although this represents an increased proportion of group A cysts as compared with the total population of cyst fluids studied over the same time period, individuals subsequently developing breast cancer were not confined to one subgroup of cysts. Androgen conjugate and growth factor content also did not predict for subsequent cancer. At the present time, it is therefore concluded that biochemical measurements in cyst fluids cannot accurately identify women likely to develop breast cancer. However, the routine aspiration of cysts does provide the opportunity to monitor the local microenvironment of the breast. PMID- 1600528 TI - Reversal of left ventricular dysfunction early after coronary artery bypass grafting. AB - This study evaluated the early effect of coronary artery bypass grafting (CABG) on left ventricular systolic function. Intraoperative echocardiography was performed in 32 patients with coronary artery disease and chronic, stable angina pectoris. Left ventricular short-axis images at mid-papillary muscle level were videotaped at similar loading conditions shortly after pericardiotomy and 28 +/- 5 min after weaning from cardiopulmonary bypass. Inotropic or vasodilator administration was avoided or suspended at least 5 min before echocardiography. The left ventricle was divided off-line into 8 segments. The ejection fraction and percent systolic wall thickening (PSWT) were calculated pre- and post-CABG. A total of 256 myocardial segments were analyzed. Any segment showing a preoperative PSWT of less than 30% was considered dysfunctional, while segments with a PSWT of greater than 30% were considered normal. After surgery, the PSWT in 162 dysfunctional segments (63%) increased from 11.8 +/- 8.9 to 24.3 +/- 14.3% (p less than 0.001). Conversely, a reverse trend was found in the remaining 94 normal segments (37%) with a decreasing PSWT from 46.2 +/- 13.8 to 33.4 +/- 14.8% (p less than 0.001). Ejection fraction also increased from 47.2 +/- 3.5 to 58.5 +/- 18.9% (p less than 0.05). Thus, CABG is followed by an immediate recovery of systolic function in dysfunctional myocardial segments, while compensatory hyperfunction is reduced in normal segments. These results indicate that the post CABG improvement in PSWT is due to redistribution of coronary blood flow, rather than to pharmacological or hormonal influences. Intraoperative echocardiography is a useful technique to monitor left ventricular function during surgery. PMID- 1600529 TI - [Propafenone versus hydroquinidine in long-term pharmacological prophylaxis of atrial fibrillation]. AB - New antiarrhythmic class 1C agents have been proposed in the last few years in an attempt to suppress paroxysmal atrial fibrillation at long-term, as the most commonly used class 1A agents such as quinidine gave highly variable results as regards both side-effects and efficacy. The aim of this randomized prospective study is to evaluate the efficacy and safety of oral propafenone at long term in preventing paroxysmal atrial fibrillation and to compare the results with those obtained using agents such as quinidine. Two hundred patients with recurrent episodes of symptomatic atrial fibrillation were enrolled for this study with entry criteria based upon a history of more than 3 crises in the previous 6 months, with electrocardiographic (standard electrocardiogram or dynamic registration) documentation. According to a randomized selection either propafenone at 300 mg twice daily or hydroquinidine retard 250 mg twice daily were administered to the patients; clinical check-up was carried out every 3 months or if clinical course worsened. The dosages were increased if proved to be inadequate at check-up (i.e. recurrence of atrial fibrillation) up to 300 mg 3 times daily for propafenone and 500 mg twice daily for hydroquinidine. The efficacy at the 3rd month was 71% for propafenone and 60% for hydroquinidine, at the 6th month 60% for propafenone and 56% for hydroquinidine; this trend lowered progressively as the follow-up continued, to 48% for propafenone and 42% for hydroquinidine (NS). More than 70% of the responder patients assumed 600 mg twice for propafenone or 250 twice for hydroquinidine. Propafenone had a percentage of 10% side-effects and hydroquinidine 24% (p = 0.02).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600530 TI - [Influence of the neurohumoral system on left ventricular performance in chronic congestive heart failure]. AB - he influence of the neurohumoral system, as adrenergic system or renin angiotensin system, on cardiac performance in heart failure is not yet know. In order to evaluate the influence of neurohumoral activation in chronic heart failure we followed 51 patients, 47 males and 4 females of mean age 58 +/- 10 years. They suffered from chronic heart failure of different origin and were classified according to NYHA classification: 42 patients were in class III and 9 were in class II. They were treated with digoxin and diuretics since long time. Ejection fraction (EF) was obtained by RVG at baseline and 8 months later. In order to test the influence of adrenergic system on EF we checked plasmatic norepinephrine levels and we divided the patients in two groups: Group A with high levels of plasmatic norepinephrine (1114 +/- 594 pg/ml) and Group B with normal level (426 +/- 139 pg/ml). Group A showed a reduction of EF (-3.73 +/- 1.27%) while, Group B showed a small increase of EF (+ 2.57 +/- 4.32%). To test the influence of renin-angiotensin system we also evaluated the patients according to the value of plasmatic renin activity: normal or high level. We did not observe a significant difference between the 2 groups. Patients with high plasmatic norepinephrine value presented a significant reduction of EF compared to those with low plasmatic norepinephrine. The adrenergic system seems to be more important than renin-angiotensin system or cardiac performance. PMID- 1600531 TI - [Myocardium-protective effects of phosphocreatine in experimental ischemia reperfusion]. AB - The protective effects of exogenous phosphocreatine were evaluated in vitro on isolated perfused rat hearts during reperfusion of ischemic myocardium. The hearts were randomly allocated in 2 groups. In the first (n 6) phosphocreatine was added at a concentration of 10 mM. The latter was utilized as control (n 7). In both groups the results showed a slight decrease in the post-ischemic myocardial performance. Aortic systolic pressure and flow respectively decreased on reperfusion by 17% and 12.5% in the phosphocreatine group and by 25.6% and 35% in the control group. Coronary flow was reduced by 10% in the phosphocreatine and by 18% in the control group. No statistically relevant differences were reported within or between the groups. No changes in heart rate occurred in the same period in the phosphocreatine and in the control group. Myocardial enzyme release during reperfusion showed significant lower levels of CK and LDH in the phosphocreatine group compared to controls (p less than 0.001 after 65 min and p less than 0.025 after 75 min between the 2 groups). The occurrence of serious ventricular arrhythmias was considerably higher in controls with respect to the phosphocreatine group. The overall incidence of major rhythm disturbances was 66% in the phosphocreatine group and 100% in the control group. Irreversible ventricular fibrillation (57%) occurred only in control hearts. The present findings indicate that phosphocreatine exerts a protective effect during myocardial ischemia and reperfusion, especially by preventing serious ventricular arrhythmias and by reducing myocardial enzyme release. PMID- 1600532 TI - [Angioplasty in unstable angina]. PMID- 1600533 TI - Platelets, endothelium-derived vasoactive factors, and coronary disease. PMID- 1600534 TI - 24-hour cardiovascular action and compliance. PMID- 1600535 TI - Role of quality of life in hypertension therapy: implication for patient compliance. AB - Although the cardiovascular risk factors associated with hypertension are well established, the effects of the disease are usually transparent to the patient. However, the impact of diagnosis and treatment are often overt and usually negative. Because of high rates of non-compliance following adverse experiences with treatment, patients are exposed to the kind of risk for which therapeutic intervention was originally intended. The nature of the impact of hypertension therapy has become more clearly defined as well-controlled, quality-of-life studies have been reported across a variety of therapeutic classes. These studies may be used to address the problem of patient compliance by (1) informing the physician about the likely effects a class of, or particular, compound might have, and (2) by providing a means by which the physician can monitor and intervene in the treatment process. By using quality-of-life information, the clinician can directly influence the impact of therapy on the patient, improve compliance with the therapeutic regimen, and reduce that patient's risk for cardiovascular events. PMID- 1600536 TI - Issues in patient compliance: the search for therapeutic sufficiency. AB - Distinguishing among biological, pharmacological, and behavioural variability is essential for proper interpretation of the therapeutic experiment at each return visit. Within the behavioural component, partial compliance refers to all suboptimal levels of concordance between the patient's behaviour and the clinical prescription. However, the assessment of compliance is limited largely by imperfect measures of medication taking which are frequently distant in time and space from the medication-taking event itself. Most studies indicate compliance levels of only 50-70% with antihypertensive regimens as well as considerable variance from day to day and person to person. Therapeutic outcome may be a misleading method to assess the sufficiency of a regimen because of the high prevalence of suboptimal medication-taking behaviour. In selected situations, prolongation of pharmacological effect may compensate for imperfect medication taking behaviour, confirmed by electronic medication monitors. Such pharmacodynamic prolongation exemplifies therapeutic sufficiency, a new paradigm for therapeutics in the 1990s. PMID- 1600537 TI - Circadian rhythms and coronary events: implications for therapy. AB - Obstructive coronary disease has many clinical expressions and some are used as useful indicators of risk. Apart from symptoms, transient ischaemia occurs during daily life, is mostly silent and represents one measure of risk. Ambulatory monitoring of the electrocardiogram shows that ischaemia occurs with increased frequency during the morning hours while waking and rising. This coincides with other damaging vascular events, increased sympathetic activity and changes in coronary blood supply and myocardial oxygen demand that may favour a lower threshold to ischaemia. Calcium blockers, beta-blockers and aspirin can favourably affect this process and long-acting drugs appear to be a more rational approach given the variability of ischaemia over time. PMID- 1600538 TI - Contemporary issues in peripheral vascular disease. PMID- 1600539 TI - Acute pulmonary embolism. PMID- 1600540 TI - Pulmonary vascular disease: primary pulmonary hypertension. AB - Clinical and pathologic features of primary pulmonary hypertension have been well characterized, but little is known regarding the underlying cause and pathogenesis. The disorder is usually discovered in its late stage, when pulmonary vascular resistance is already severely compromised and the pathologic changes already well developed. It is not surprising, then, that most attempts at defining effective pharmacologic interventions have been disappointing. Some new approaches are clearly needed. The past decade has witnessed the rapid growth of molecular techniques in areas applied to the study of the blood vessel wall, blood coagulation, and the platelet-endothelial cell interaction. Platelet derived growth factors and other macrophage-derived factors may play important roles in the pathogenesis of the early proliferative lesions found in the small pulmonary arterioles. Other vascular-derived mediators may be important determinants in modulating the vasoconstrictor or vasodilator response in small vessels. A recent brief but pertinent review has highlighted some of the new directions being taken. It appears that the right questions are finally being asked, and we now may have the tools to answer them. PMID- 1600541 TI - Arteriovenous communications. PMID- 1600542 TI - Vasospastic disorders. PMID- 1600543 TI - Occlusive arterial disease of the upper extremity. AB - Occlusive and aneurysmal diseases of the large vessels of the upper extremity are uncommon experiences in most practices. Yet, by utilizing basic principles learned in the lower extremity that emphasize proper historic and physical examination, and by the selective use of angiography, these problems can be delineated and effectively treated. Some of the variations in anatomic location and the natural histories of some conditions more prevalent in the upper extremity have been emphasized. PMID- 1600544 TI - Vascular diseases of the cervical carotid artery. PMID- 1600545 TI - Aneurysmal disease. AB - The frequency of the diagnosis of arterial aneurysms is increasing. Aneurysms in many locations remain asymptomatic and require careful evaluation of at-risk patient populations. Screening of first-degree relatives of patients with known AAA now appears to be indicated. A high index of suspicion of the possible presence or the existence of known aneurysms should prompt timely referral for evaluation by a vascular surgeon. Consideration of a patient's candidacy for surgical intervention should involve the evaluation of a myriad of factors, some of which have been elucidated in this overview. The safety of surgical intervention for aneurysm repair has continued to improve, and most patients can be surgically managed with an acceptably low rate of morbidity and mortality. PMID- 1600546 TI - Primary hypercoagulable state. PMID- 1600547 TI - Penetrating aortic ulcer. PMID- 1600548 TI - Conservative management of occlusive peripheral arterial disease. PMID- 1600549 TI - The noninvasive vascular laboratory. PMID- 1600550 TI - Endothelium-derived factors and peripheral vascular disease. AB - The endothelium plays a major role in modulating vascular tone, vascular growth, and interactions of the vessel wall with blood constituents. Therefore, abnormalities in endothelial function may play a primary or contributory role to a variety of vasculopathies that are characterized by thrombosis, excessive vasoconstriction, or vascular smooth muscle proliferation. Our increasing understanding of the complexity of endothelial functions will permit us to understand the mechanisms of vascular disease and to design new therapies directed at these mechanisms of disease. PMID- 1600551 TI - Acute deep venous thrombosis. PMID- 1600552 TI - Chronic venous insufficiency. PMID- 1600553 TI - Surgical treatment of venous disease. PMID- 1600554 TI - Postnatal development of the hypothalamic ventromedial nucleus: neurons and synapses. AB - 1. In this report the postnatal differentiation of the hypothalamic ventromedial nucleus (VMN) was studied. The main maturational changes detected at the fine structural level occurred between 10 and 20 days of postnatal life. 2. In 5-day old rats the majority of neurons was undifferentiated, with rudimentary cytoplasmic organelles. Dendritic profiles presented an empty appearance due to an electron-lucent matrix and scarce content of organelles. 3. At 10 days there was a significant proliferation of cytoplasmic organelles in the perikaryon, mainly of those involved in protein biosynthesis as the rough endoplasmic reticulum (RER) and the Golgi complex. 4. After 20 days of age the VMN neurons acquired the cytological appearance of adult neurons, with well-organized RER, Golgi complexes, and pleomorphic mitochondria. Concurrent with these changes, there was a marked development of other organelles in the neuropil, which was accompanied by an increase in synaptic density and differentiation of their subsynaptic structures. PMID- 1600555 TI - Long-term effects of constant light or darkness on chicken pineal hydroxyindole-O methyltransferase expression: biochemical and cellular aspects. AB - 1. Chickens kept in constant light, as opposed to constant darkness, display a twofold increase in the activity of pineal hydroxyindole-O-methyltransferase (HIOMT), the last acting enzyme in the melatonin pathway. 2. Using an immunological approach, we presently show that this regulation of HIOMT activity reflects changes in the concentration of a single molecular form of the enzyme protein (a 38 kDa polypeptide). Immunohistofluorescence indicates that these concentration changes concurrently affect modified photoreceptors and pinealocyte like cells in the chicken pineal organ. 3. Together, the present data support the hypothesis that environmental lighting might regulate the expression of the HIOMT gene. PMID- 1600556 TI - Modulation of nicotinic acetylcholine receptor channel by pH: a difference in pH sensitivity of Torpedo and mouse receptors expressed in Xenopus oocytes. AB - 1. In this study, effects of pH on the ion channel function of nicotinic acetylcholine receptor (nAChR) from Torpedo californica electroplax and mouse muscle BC3H-1 cells were investigated using Xenopus laevis oocytes injected with in vitro synthesized RNA transcripts. The acetylcholine (ACh)-induced whole-cell peak current responses and slow desensitization rates were measured by voltage clamp. 2. The ACh-induced peak currents of Torpedo nAChRs were reversibly diminished when extracellular pH was reduced from 7.4 to 5.0 and increased at pH greater than 7.4. This pH dependence had an apparent pKa of 7.0. In contrast, the peak current of mouse muscle nAChRs were reversibly decreased at both acidic and alkaline pH's. This bell-shaped pH profile with a maximum at pH 7.4 had two apparent pKa values of 5.6 and 9.2. 3. The peak current responses of four mouse Torpedo nAChR hybrids consisting of three Torpedo subunits and one mouse nAChR subunit displayed similar pH profiles at acidic pH, with a pKa of 6.0 to 6.5, which lay between the pKa 5.6 for mouse and the pKa 7.0 for Torpedo nAChRs. Two of these combinations, alpha M beta T gamma T delta T and alpha T beta T gamma M delta T, also had an alkaline pH dependence of the current response similar to that of mouse receptor, with a pKa of 9.3 to 9.5. 4. The slow desensitization rate of Torpedo nAChRs increased at both acidic and alkaline pH's, with two pKa values of 6.5 and 9.5, whereas that of mouse muscle receptors remained unchanged from pH 6.5 to pH 9.0 and increased at pH less than 6.0, with a pKa of 4.7. 5. Substitution of each subunit of Torpedo nAChR with a mouse counterpart resulted in a pH dependence pattern (pKa 6.0 to 6.4 and pKa 9.1 to 9.3) similar to that of Torpedo nAChR except the substitution with mouse beta subunit (pKa 4.8 and pKa 8.9), which appears to carry the characteristic acidic group determining the pH dependence of mouse nAChR desensitization. 6. The apparent pKa values obtained from the pH dependence studies of nAChR channel activation and desensitization suggest the involvement of different amino acid residues in determining channel functions of Torpedo and mouse nAChRs. The groups with pKa 7.0 and 6.5 on Torpedo nAChR can be tentatively identified as His residues, whereas those with pKa 5.6 and 4.7 on mouse receptor as Glu or Asp residues. The alkaline pKa of 8.9 to 9.5 may be Cys, Tyr, or Lys. PMID- 1600558 TI - Appearance of an intra-acrosomal antigen during the terminal step of spermiogenesis in the rat. AB - In a survey of sperm antigens in the rat, a new intra-acrosomal antigen was found using a monoclonal antibody MC41 raised against rat epididymal spermatozoa. The MC41 was immunoglobulin G1 and recognized spermatozoa from rat, mouse and hamster. Indirect immunofluorescence with MC41 specifically stained the crescent region of the anterior acrosome of the sperm head. Immuno-gold electron microscopy demonstrated that the antigen was localized within the acrosomal matrix. Immunoblot study showed that MC41 recognized a band of approximately 165,000 dalton in the extract of rat sperm from the cauda epididymidis. Immunohistochemistry with MC41 demonstrated that the antigen was first detected in approximately step-2 spermatids, and distributed over the entire cytoplasmic region of spermatids from step 2 to early step 19. The head region became strongly stained in late step-19 spermatids and then in mature spermatozoa. Distinct immunostaining was not found in the developing acrosome of spermatids throughout spermiogenesis. These results suggest that the MC41 antigen is a unique intra-acrosomal antigen which is accumulated into the acrosome during the terminal step of spermiogenesis. PMID- 1600557 TI - Electric organ polyamines and their effects on the acetylcholine receptor. AB - 1. The electric organ of Torpedo nobiliana contained putrescine (PUT), spermidine (SPD), spermine (SPM), and cadaverine (CAD). Traces of acetylated SPD and SPM were occasionaly seen. 2. Upon fractionation of the tissue by differential centrifugation, the polyamines (PA) were found predominantly in the soluble fraction. The postsynaptic membrane fraction, containing a high concentration of acetylcholine receptor (AChR), was proportionally enriched in SPM. The molar ratio of SPM to AChR was approximately two in these membranes. 3. The effect of exogeneous PA on AChR function was studied by two methods: carbamoylcholine (CCh) dependent 86Rb+ influx into receptor-rich membrane vesicles and [alpha 125I]bungarotoxin (Bgt) binding to the AChR. 4. SPM inhibited both ion influx and the rate of Bgt binding at concentrations above 1 mM, and therefore it appears to act as a competitive antagonist of the AChR. 5. At submicromolar concentrations, and only after preincubation with the receptor-rich membrane, SPM and PUT increased the ion influx by about 20% over control values. 6. Preincubation with 100 nM SPM did not affect the equilibrium binding of iodinated toxin or the rate of toxin binding, and therefore SPM was not uncovering new receptors. 7. By measuring the initial rate of toxin binding after different periods of preincubation with 1 microM CCh, the rate of the slow phase of receptor desensitization was determined. This rate was not changed by 100 nM SPM. 8. Although these results suggest that at low concentrations SPM is a positive modulator of the AChR, the precise mechanism of action is not determined yet. PMID- 1600559 TI - Sulfhydryl oxidase immunoreactivity in seminiferous tubules of infertile men. AB - Sulfhydryl oxidase (SOx) immunoreactivity was investigated in the seminiferous epithelium of human biopsy material from the testes of 33 adult men with disturbed fertility. SOx immunoreactivity was expressed in normal seminiferous epithelium in type-A spermatogonia (27 +/- 4% of all spermatogonia) (n = 4), in spermatocytes and round spermatids. Mature spermatozoa as well as Sertoli cells were unlabelled. Within the interstitium, Leydig cells were immunopositive. In biopsies of oligozoospermic men showing hypospermatogenesis (n = 24), an increase in labelled spermatogonia up to more than 90% was observed in biopsies, where seminiferous epithelia revealed only spermatogonia and Sertoli cells. Within the group of oligozoospermic patients there was a significant increase of labelled spermatogonia from 43 +/- 13% (greater than 20 mill/ejaculate) (n = 7) to 55 +/- 16% (less than 20 and greater than 10 mill/ejaculate) (n = 6) to 68 +/- 8% (less than 5 mill/ejaculate) (n = 11) and a significant (P = 0.01) decrease of score count from 7.0 +/- 2.7 to 2.0 +/- 1.8. In this group the increase of labelled spermatogonia was correlated with sperm concentrations in the ejaculate (correlation coefficient: r = -0.6). In biopsies of azoospermic patients showing maturation arrest at the level of spermatocytes or spermatids (n = 5) the percentage of labelled spermatogonia was within the range of 24% to 59%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600560 TI - Distribution of histamine in the rat kidney during pregnancy and development. AB - An antiserum against conjugated histamine and two oligonucleotide probes that detect the mRNA encoding L-histidine decarboxylase (HDC) involved in histamine synthesis were used to study the appearance of histamine and its location in the kidneys of fetal, newborn and young postnatal rats and in the kidneys of pregnant rats. On embryonic days 16 and 18 (E16 and E18), some HA-immunoreactive (HA-ir) cells were found within the largest S-shaped bodies. Histamine was found to appear rapidly between the 18th and 20th embryonic days in the convoluted tubules of the kidneys. On postnatal day 0 (P0), the distal convoluted tubules and collecting ducts exhibited bright fluorescence, the intensity of which decreased quickly so that it was faint on day P4 and absent at later stages. In kidneys of pregnant rats HA-ir was found in the epithelium of both the Bowman's capsule, collecting ducts and in a few cells within the tubules. Nonuniform HA-ir was also detected within glomeruli. No evidence for the presence of L-histidine decarboxylase mRNA in kidneys of fetuses or pregnant rats was seen. It is concluded that distinct structures in the developing rat kidney contain histamine during a period around birth from day E20 to day P4. In the pregnant rat, the epithelium that is in direct contact with the urine flow is immunoreactive for histamine from day 16 to 20 of pregnancy. The results suggest that histamine is not synthesized locally in the kidneys but rather originates from other tissues. PMID- 1600561 TI - Ontogeny of histamine-immunoreactive cells in rat stomach. AB - An antiserum against hemocyanin-conjugated histamine was used to study the cellular stores of histamine in the stomach, especially the oxyntic mucosa, of fetal and early postnatal rats. Tissues were fixed in 4% 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide (EDC-DI) and standard immunofluorescence technique was used. Histamine was first detected on the 16th embryonic (E16) day when a few histamine-immunoreactive (HA-ir) cells and nerve fibers were observed in the muscular layer of the stomach wall. On day E18, HA-ir cells were visualized for the first time in the oxyntic mucosa of the stomach, and from that day on the number of such cells increased slowly initially and after day E20 more rapidly. At birth many of the HA-ir cells in the oxyntic mucosa possessed processes giving them a paracrine-like appearance typical of enterochromaffin-like cells (ECL cells). Only a very small number of the HA-ir cells represented metachromatically stained mast cells and were located in the submucosa. After birth, the number of HA-ir ECL cells increased steadily, until day 21 when the distribution and number was very similar to that of the adult. The results suggest that histamine containing neurons and ECL cells appear in the stomach wall before birth, and that there are histamine-containing ECL cells in the mucosa and mast cells in the submucosa of the stomach wall at birth. PMID- 1600562 TI - Localization of luteinizing hormone beta-mRNA by in situ hybridization in the sheep pars tuberalis. AB - The localization of luteinizing hormone beta (LH beta)-mRNA was studied by in situ hybridization in the pars tuberalis of sheep using a homologous sheep double stranded 32P- or 35S-cDNA. The labelled cDNA probe detected one mRNA sequence in the pars tuberalis by Northern blot analysis; this sequence was similar to that detected in the pituitary. In situ, the labelling of LH beta-mRNA in the horizontal and sagittal tissue sections was found throughout the pars tuberalis. This labelling was prevented by adding an excess of cold probe or treating the sections by ribonuclease before in situ hybridization. Controls showed a labelling in the pars distalis, but not in the median eminence, hypothalamus, cerebral cortex and liver sections. Double labelling by in situ hybridization followed by immunohistochemistry using a specific LH beta-antiserum indicated that the labelling of LH beta-mRNA appeared more intense in LH-containing cells that were found only in the ventral part of the pars tuberalis. These results suggest that the entire pars tuberalis is able to produce the LH beta subunit, but that the level of translation greatly varies according to the location of the cells. PMID- 1600564 TI - Initial formation of cellular intrinsic fiber cementum in developing human teeth. A light- and electron-microscopic study. AB - The present study describes the formative process of the initiation of cellular intrinsic fiber cementum (CIFC) in still growing human teeth. From 29 premolars and molars with incomplete roots developed to 60-90% of their final length, 8 premolars (with roots formed to three quarters of their final length) were selected for electron-microscopic investigation. All teeth were clinically intact and prefixed in Karnovsky's fixative immediately after extraction. Most of them were decalcified in ethylene diaminetetraacetic acid (EDTA), and the apical part of the roots was divided axially into mesial and distal portions that were subdivided in about 5 slices each. Following osmication and embedding in Epon, these blocks were cut for light- and electron-microscopic examination. In addition, 5 teeth with incomplete roots were freed from organic material and processed for scanning electron microscopy. It was found that CIFC-initiation commenced very close to the advancing root edge and resulted in a rapid cementum thickening. Thereafter, appositional growth continued on the already established cementum surface. Large, basophilic and rough endoplasmic reticulum-rich cementoblasts, some of which became cementocytes, were responsible for both fast and slow CIFC-formation. The CIFC-matrix was free of Sharpey's fibers and composed of more or less organized intrinsic collagen fibrils, in part fibril bundles, that ran roughly parallel to the root surface. Initially, the cementum fibrils intermingled with those of the dentinal collagen fibrils, which were not yet mineralized. This boundary subsequently underwent calcification. The development of collagen fibril bundles and their extracellular arrangement were associated with cytoplasmic processes probably involved in fibril formation and fibril assembly. Many cementoblasts contained intracytoplasmic, membrane-bounded collagen fibrils, which probably were related to fibril formation rather than degradation. PMID- 1600563 TI - Postnatal development of von Ebner's glands: accumulation of a protein of the lipocalin superfamily in taste papillae of rat tongue. AB - Antibodies produced against rat von Ebner's gland (VEG) protein, a recently characterized member of a lipophilic ligand carrier protein family, detect this protein immunocytochemically in von Ebner's gland acini and show that it is present at high concentrations in the clefts of circumvallate and foliate papillae. During embryonic development, von Ebner's gland anlagen are innervated (as shown immunocytochemically using neuronal specific antibodies) as early as embryonic day 20, before lateral glandular outgrowth and VEG protein can be observed. Expression of the VEG protein as determined by in situ hybridization and immunocytochemistry begins at postnatal day-2 cells in differentiating and branching off from von Ebner's gland ducts, and sharply increases with further enlargement and maturation of the gland. The close temporal correlation of von Ebner's gland innervation and VEG protein expression with papilla innervation and taste-bud development suggests a functional relationship of both structures. VEG protein might control access of lipophilic sapid molecules, such as bitter substances, to the gustatory receptors. PMID- 1600565 TI - Development of cytoplasmic digitations between Leydig cells and testicular macrophages of the rat. AB - Testicular macrophages and Leydig cells from adult animals are known to be functionally coupled. For example, secreted products from macrophages stimulate testosterone secretion by Leydig cells. In adult rat testes, structural coupling also exists between these cells. This coupling consists of cytoplasmic projections from Leydig cells located within cytoplasmic invaginations of macrophages. Although macrophages are known to exist in the testis in immature animals, it is not known when these digitations develop. The purpose of the present study was to determine whether the time of their development coincides with known maturational events that occur in Leydig cells, particularly during the peripubertal period. Testes from rats at 20, 30 and 40-days-of-age as well as testes from mature rats weighing more than 500 gm were prepared for ultrastructural analysis. It was found that digitations form between 20 and 30 days-of-age. These structures varied from simple tubular projections to complicated branched structures, suggesting that digitations are more than simple invaginations of microvilli into coated vesicles as previously described. Subplasmalemmal linear densities were also observed within macrophages juxtaposed to Leydig cells. Collagen was commonly observed between macrophages and Leydig cells in animals 20 days old. These studies demonstrate that although macrophages are present in the testis in maximal numbers at 20 days-of-age, they do not form junctions with Leydig cells until day 30. This is just prior to the major increase in secretory activity of rat Leydig cells that occurs during puberty. PMID- 1600566 TI - Distribution of arginine vasotocin in the brain of the lizard Anolis carolinensis. AB - The distribution of immunoreactive arginine vasotocin (AVT-ir) was determined in the brain of the lizard Anolis carolinensis. Cells and fibers containing AVT-ir were found in the medial septal region, lamina terminalis, lateral forebrain bundle, preoptic area, supraoptic nucleus, anterior hypothalamus, paraventricular nucleus, periventricular nucleus, arcuate nucleus, and ventromedial nucleus of the thalamus. Occasional AVT-ir cells were found in the interpeduncular nucleus. Fibers containing AVT-ir were found in the cortex, around the olfactory ventricle, in the diagonal band of Broca, amygdala area, dorsal ventricular ridge, striatum, nucleus accumbens, septum, ventromedial hypothalamus, lateral hypothalamus, medial forebrain bundle, median eminence, pars nervosa, nucleus of the solitary tract, locus coeruleus, cerebellar cortex (granular layer), dorsal part of the nucleus of the lateral lemniscus, substantia nigra, and myelencephalon. The intensity of AVT-ir staining was, in general, greater in males than in females. Comparison of AVT-ir distribution in A. carolinensis with those previously published for other reptilian species revealed species-specific differences in distribution of AVT. PMID- 1600567 TI - Blood transfusion and haemostatic management in the perioperative period. PMID- 1600568 TI - Addiction and the anaesthesia resident. AB - Addiction to narcotics appears to be a problem in the specialty of anaesthesia and particularly in anaesthesia residents. In 1992, this problem is perceived to be a treatable disease for which there is help and there is hope. None of us are immune to this disease. One of the key features of this disease is that the person who is afflicted cannot reach out for help. Thus, it is our responsibility as caring, concerned, and hopefully compassionate colleagues to reach out to them. With proper intervention, treatment, support of family, colleagues and department, and with a tightly monitored aftercare contract, addicted anaesthetists can successfully return to the specialty. PMID- 1600569 TI - Perioperative respiratory assessment and management. AB - There have been many recent advances in the understanding and therapy of respiratory diseases. This review has attempted to cover some of the relevant new information about those disorders most likely to be encountered by anaesthetists. PMID- 1600570 TI - Analgesia methods during labour and delivery. PMID- 1600571 TI - The anaesthetic management of neurosurgical emergencies. PMID- 1600572 TI - Regional anaesthesia for ambulatory surgery. PMID- 1600573 TI - The compromised airway: recognition and management. PMID- 1600574 TI - Anaesthetic management of the child with congenital heart disease for non-cardiac surgery. PMID- 1600575 TI - The pulmonary artery catheter: when and why it should be used. PMID- 1600576 TI - Oxygen concentrators and the practice of anaesthesia. PMID- 1600577 TI - The diagnosis and perioperative management of myocardial ischaemia. PMID- 1600578 TI - Tuberculosis: a global overview of the situation today. AB - The overall tuberculosis situation in the world in 1990 and its recent trends are reviewed by an analysis of the case notifications to WHO and tuberculosis mortality reports. Estimates of the prevalence of tuberculosis infection and the incidence of tuberculosis disease and deaths predicted in 1990 were carried out with simple epidemiological models. Approximately one third of the world's population is infected with Mycobacterium tuberculosis. In the past decade, an average of 2.5 to 3.2 million cases were notified every year globally, the small decrease in notification rates in recent years being offset by population growth. In 1990, an estimated 8 million people developed tuberculosis worldwide and 2.6 to 2.9 million died. The majority of these cases and deaths occurred in Asia, with an increasing number among HIV-infected individuals, especially in Africa where an upward trend is clearly detectable. Data on tuberculosis cases notified by WHO Member States demonstrate the magnitude of the problem but must be interpreted with caution. Being less than the expected incidence, they reflect the inadequacies of tuberculosis control programmes. This review confirms the very high global magnitude of the tuberculosis problem and calls for an urgent revitalization of tuberculosis control programmes throughout the world. PMID- 1600579 TI - Prevention and control of neurofibromatosis: memorandum from a joint WHO/NNFF meeting. AB - Neurofibromatosis (NF) is a serious, common, genetically determined neurological disorder; with a prevalence of about 1:4000 births it affects both sexes and all races and ethnic groups. The two major forms are referred to as NF1 and NF2, as suggested in 1987 by a National Institutes of Health Consensus Development Conference on Neurofibromatosis. In NF1, the disease phenotype is more variable and complex than in NF2. Complications can occur in any of the body systems in tissues of ectodermal, mesodermal and neural tube origin; there is marked variation of disease phenotype even within families. The NF2 gene, in contrast, only seems to be expressed in tissues of ectodermal origin and its expression is more uniform both within and between families. The recent discovery and isolation of the gene responsible for the NF1 mutation has practical applications in the field of molecular genetics which could modify the approaches for diagnosis, treatment and prevention of NF. This Memorandum summarizes the discussions and recommendations of the participants at a joint WHO/National Neurofibromatosis Foundation (NNFF) meeting, held in Jacksonville, Florida, USA, on 27-28 January 1991. PMID- 1600580 TI - Public health issues related to animal and human spongiform encephalopathies: memorandum from a WHO meeting. AB - The transmissible spongiform encephalopathies (TSE) include bovine spongiform encephalopathy (BSE), which was first described in 1986 in the United Kingdom but has occurred subsequently in several other countries. This Memorandum reviews the existing state of knowledge on all the known spongiform encephalopathies, and evaluates the pathways of transmission and associated hazards. The possible implications of the animal diseases, especially BSE, with regard to the use of animal tissues as animal feed, human food, and in the preparation of medicinal and other products for human use are discussed, with recommendations to national health authorities on appropriate measures to minimize the consequences of BSE to public and animal health. PMID- 1600581 TI - WHO programme for the prevention of rheumatic fever/rheumatic heart disease in 16 developing countries: report from Phase I (1986-90). WHO Cardiovascular Diseases Unit and principal investigators. AB - The programme was initiated in 1984 by WHO in close collaboration with the International Society and Federation of Cardiology (ISFC). Sixteen countries in five WHO Regions participated: Mali, Zambia and Zimbabwe (in Africa); Bolivia, El Salvador and Jamaica (in the Americas); Egypt, Iraq, Pakistan and Sudan (in the Eastern Mediterranean); India, Sri Lanka and Thailand (in South-East Asia); and China, the Philippines and Tonga (in the Western Pacific). The programme was planned for implementation in three phases: pilot study and control programme in a selected area, control programmes in all the selected communities, and their extension to the whole country. In Phase I, a total of 1,433,710 schoolchildren were screened and 3135 cases of rheumatic fever/rheumatic heart disease (RF/RHD) were found, giving a prevalence of 2.2 per 1000 (higher in the African and Eastern Mediterranean regions); 33,651 recently identified or already known cases were registered; completion of secondary prophylaxis was irregular but averaged 63.2% coverage; percentages of adverse reactions (0.3%) and recurrence of acute RF (0.4%) were very small; 24,398 health personnel and teachers were trained. Health education activities were organized for patients, their relatives, and the general public in hundreds of health education sessions. Thousands of pamphlets, brochures and posters were distributed, and health education programmes were broadcast on radio and television. The quality of care for RF/RHD patients improved under the programme, which has been expanded to other areas. PMID- 1600582 TI - Mortality and cataract: findings from a population-based longitudinal study. AB - The study was carried out in a rural population in central India. A random sample of 11 village communities provided 1020 persons aged 40-64 years, who were examined in 1982 and again reassessed in 1986. Statistical analysis, based on the Mantel-Haenszel method for stratified data, showed increased mortality in persons who had central lens opacities, compared with those who had trivial or no central lens opacities. The significant age-adjusted death ratio was just over 2 (2.2), as were the age/sex-adjusted and age/vision-adjusted estimates, which indicate doubling of mortality in the cataract cohort. Multiple regression analysis using the Cox proportional-hazards model gave very similar results. Statistical tests for homogeneity of death ratios across the various age/sex/vision strata were carried out, and the observed association between cataract and mortality was found to be consistent, both in males and in females, in the youngest and oldest age groups, and among those with adequate vision of 6/18 or better as well as among persons with serious visual impairment. There were no known diabetics in the study sample, which came from what could reasonably be regarded as a non diabetic population. PMID- 1600583 TI - Vitamin A deficiency and attributable mortality among under-5-year-olds. AB - Reported are estimates of the prevalence in developing countries of physiologically significant vitamin A deficiency and the number of attributable deaths. The WHO classification of countries by the severity and extent of xerophthalmia was used to categorize developing countries by likely risk of subclinical vitamin A deficiency. Using vital statistics compiled by UNICEF, we derived population figures and mortality rates for under-5-year-olds. The findings of vitamin A supplementation trials were applied to populations at-risk of endemic vitamin A deficiency to estimate the potential impact of improved vitamin A nutriture in reducing mortality during preschool years. Worldwide, over 124 million children are estimated to be vitamin A deficient. Improved vitamin A nutriture would be expected to prevent approximately 1-2 million deaths annually among children aged 1-4 years. An additional 0.25-0.5 million deaths may be averted if improved vitamin A nutriture can be achieved during the latter half of infancy. Improved vitamin A nutriture alone could prevent 1.3-2.5 million of the nearly 8 million late infancy and preschool-age child deaths that occur each year in the highest-risk developing countries. PMID- 1600584 TI - Comparison of the immune response of four different dosages of a yeast recombinant hepatitis B vaccine in Singapore children: a four-year follow-up study. AB - The immunogenicity of four different dosages of yeast-derived hepatitis B vaccine (Merck, Sharp & Dohme: 0.6 micrograms, 1.25 micrograms, 2.5 micrograms and 5.0 micrograms), administered at 0, 1 and 6 months (0-1-6 schedule) intramuscularly, was evaluated in 122 seronegative healthy children 1-12 years of age. Three months after the first dose, 83.9-100% of the vaccinees seroconverted. Peak geometric mean titres (GMT) of between 1088 mlU/ml and 1699 mlU/ml were attained 3 months after completion of the vaccination schedule. After 24 months, anti-HBs (antibody to hepatitis B surface antigen) was detected in 93.1-100% of the vaccinees, but the GMT dropped to between 214.3 mlU/ml and 303.5 mlU/ml. After 48 months, 88.8-100% of the vaccinees continued to possess anti-HBs and 70.3-87% had titres above 10 mlU/ml. As expected, the GMT declined further to between 72.6 mlU/ml and 118.8 mlU/ml. There were no significant differences in seroconversion rates and GMT among the different dosage groups. All the vaccinees remained asymptomatic and free from hepatitis B virus infection. The study showed that reduced dosages of the vaccine (0.6 micrograms, 1.25 micrograms and 2.5 micrograms) were as immunogenic as the standard dose (5 micrograms); the 2.5 micrograms dose was recommended for the national childhood immunization programme in Singapore. No booster is necessary for at least four years after vaccination. PMID- 1600585 TI - A case-control study of injuries arising from the earthquake in Armenia, 1988. AB - The study attempts to identify predictors of injuries among persons who were hospitalized following the Armenian earthquake of 7 December 1988. A total of 189 such individuals were identified through neighbourhood polyclinics in the city of Leninakan and 159 noninjured controls were selected from the same neighbourhoods. A standardized interview questionnaire was used. Cases and controls shared many social and demographic characteristics; however, 98% of persons who were hospitalized with injuries were inside a building at the time of the earthquake, compared with 83% of the controls (odds ratio = 12.20, 95% confidence interval (CI) = 3.62-63.79). The odds ratio of injuries for individuals who were in a building that had five or more floors, compared with those in lower buildings, was 3.65 (95% CI = 2.12-6.33). Leaving buildings after the first shock of the earthquake was a protective behaviour. The odds ratio for those staying indoors compared with those who ran out was 4.40 (95% CI = 2.24-8.71). PMID- 1600586 TI - Impact of height and weight on life span. AB - The study was conducted to evaluate one aspect of the entropy theory of aging, which hypothesizes that aging is the result of increasing disorder within the body, and which predicts that increasing mass lowers life span. The first evaluation of the impact of human size on longevity or life span in 1978, which was based on data for decreased groups of athletes and famous people in the USA, suggested that shorter, lighter men live longer than their taller, heavier counterparts. In 1990, a study of 1679 decreased men and women from the general American population supported these findings. In the present study data on the height, weight, and age at death of 373 men were obtained from records at the Veterans Administration Medical Center, San Diego, CA, USA. Men of height 175.3 cm or less lived an average of 4.95 years longer than those of height over 175.3 cm, while men of height 170.2 cm or less lived 7.46 years longer than those of at least 182.9 cm. An analysis by weight difference revealed a 7.72-year greater longevity for men of weight 63.6 kg or less compared with those of 90.9 kg or more. This corroborates earlier evidence and contradicts the popular notion that taller people are healthier. While short stature due to malnutrition or illness is undesirable, our study suggests that feeding children for maximum growth and physical development may not add to and may indeed be harmful to their long-term health and longevity. PMID- 1600587 TI - Toxic and trace elements in tobacco and tobacco smoke. AB - While the harmful health effects of carbon monoxide, nicotine, tar, irritants and other noxious gases that are present in tobacco smoke are well known, those due to heavy metals and other toxic mineral elements in tobacco smoke are not sufficiently emphasized. Tobacco smoking influences the concentrations of several elements in some organs. This review summarizes the known effects of some trace elements and other biochemically important elements (Al, As, Cd, Cr, Cu, Pb, Mn, Hg, Ni, Po-210, Se, and Zn) which are linked with smoking. Cigarette smoking may be a substantial source of intake of these hazardous elements not only to the smoker but also, through passive smoking, to nonsmokers. The adverse health effects of these toxic elements on the fetus through maternal smoking, and on infants through parental smoking, are of special concern. PMID- 1600588 TI - Testing for HIV antibody in serum pools. PMID- 1600589 TI - Ifosfamide, vincristine, doxorubicin and dacarbazine in adult patients with advanced soft-tissue sarcoma. AB - A total of 37 adult patients with locally advanced or metastatic soft-tissue sarcoma (STS) entered a pilot study of combination chemotherapy based on the CYVADIC (cyclophosphamide, vincristine, doxorubicin, and dacarbazine) regimen, in which cyclophosphamide was replaced by ifosfamide and mesna (1 g/m2 ifosfamide given daily on days 1-5 as 2-h infusions, 1.5 mg/m2 vincristine given on day 1 as a bolus injection, 50 mg/m2 doxorubicin given on day 1 as a 5-min infusion, and 250 mg/m2 dacarbazine given daily on days 1-5 as 30-min infusions). The overall response rate in 24 patients who were evaluable for response was 46% [95% confidence interval (CI), 25%-67%] and that in subjects who had not undergone prior chemotherapy was 50% (CI, 27%-73%). In all, 4 patients achieved a complete response (17%; CI, 5%-37%) and 2 remain in remission; 3 additional subjects were surgically rendered disease-free after they had shown a partial response. Overall, 31 patients were evaluable for toxicity. Toxicity was mainly hematological; in 3 patients the nadir WBC was less than 0.5 x 10(9)/l, and in 2 cases the nadir platelet count was less than 50 x 10(9)/l. During neutropenia, infections requiring intravenous antibiotics occurred in 8 patients (26%) and in 14 of 190 cycles (7.5%); 1 of these was fatal. We conclude that this new regimen offers promise for the treatment of advanced STS, producing acceptable toxicity. PMID- 1600590 TI - Alkylphosphocholines: influence of structural variation on biodistribution at antineoplastically active concentrations. AB - Hexadecylphosphocholine (HPC) and octadecylphosphocholine (OPC) show very potent antitumor activity against autochthonous methylnitrosourea-induced mammary carcinomas in rats. The longer-chain and unsaturated homologue erucylphosphocholine (EPC) forms lamellar structures rather than micelles, but nonetheless exhibits antineoplastic activity. Methylnitrosourea was used in the present study to induce autochthonous mammary carcinomas in virgin Sprague-Dawley rats. At 6 and 11 days following oral therapy, the biodistribution of HPC, OPC and EPC was analyzed in the serum, tumor, liver, kidney, lung, small intestine, brain and spleen of rats by high-performance thin-layer chromatography. In contrast to the almost identical tumor response noted, the distribution of the three homologues differed markedly. The serum levels of 50 nmol/ml obtained for OPC and EPC were much lower than the value of 120 nmol/ml measured for HPC. Nevertheless, the quite different serum levels resulted in similar tumor concentrations of about 200 nmol/g for all three of the compounds. Whereas HPC preferably accumulated in the kidney (1 mumol/g), OPC was found at increased concentrations (400 nmol/g) in the spleen, kidney and lung. In spite of the high daily dose of 120 mumol/kg EPC as compared with 51 mumol/kg HPC or OPC, EPC concentrations (100-200 nmol/g) were low in most tissues. High EPC concentrations were found in the small intestine (628 nmol/g). Values of 170 nmol/g were found for HPC and OPC in the brain, whereas the EPC concentration was 120 nmol/g. Obviously, structural modifications in the alkyl chain strongly influence the distribution pattern of alkylphosphocholines in animals. Since EPC yielded the highest tissue-to-serum concentration ratio in tumor tissue (5.1) and the lowest levels in other organs, we conclude that EPC is the most promising candidate for drug development in cancer therapy. PMID- 1600591 TI - Chemosensitivity of human MCF-7 breast cancer cells to diastereoisomeric diaqua(1,2-diphenylethylenediamine) platinum(II) sulfates and specific platinum accumulation. AB - Cisplatin, raceme-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine]platinu m(II) sulfate (compound I), meso-diaqua[1,2-bis(4-fluorophenyl)ethylenediamine] platinum(II) sulfate (compound II), and meso-diaqua[1,2-bis(2,6-dichloro-4- hydroxyphenyl)ethylenediamine]platinum(II) sulfate (compound III) were compared with regard to their effect on the MCF-7 breast cancer cell line in vitro. At equimolar concentrations (5 microM), cisplatin, compound I, and compound II were equiactive after 231 h drug exposure, whereas compound III was ineffective. Although compounds I and II showed markedly greater inactivation than did cisplatin after 6 h incubation with culture medium, compound I (but not compound II) exhibited antitumor activity equivalent to that of cisplatin when cells were exposed to the drugs for 6 h. Platinum measurements by neutron-activation analysis revealed that compound I was selectively and rapidly accumulated by MCF 7 cells, resulting in a high degree of DNA platination within the first few hours of drug exposure. However, when the drug-exposure period was long enough, platinum enrichment was not reflected in an overall difference in the cytotoxicity of compound I vs cisplatin. Nevertheless, compound I should be superior to cisplatin in vivo, provided that effective plasma levels can be maintained for about 6 h. PMID- 1600592 TI - Phenotypic analysis of 1-B-D-arabinofuranosylcytosine deamination in patients treated with high doses and correlation with response. AB - Two phenotypes for 1-B-D-arabinofuranosylcytosine (ara-C) deamination corresponding to a ratio of distribution for "slow" (ratio, less than or equal to 14) vs "fast" (ratio, greater than 14) deaminators of 70%:30%, have been determined on the basis of studies on plasma ratios of 1-B-D arabinofuranosyluracil/ara-C (ara-U/ara-C) in 56 subjects treated with high-dose ara-C (3 g/m2 infused i.v. over 3 h). A positive correlation of age with the concentration of ara-U was observed. In a subgroup of 36 patients with leukemia, the ara-U/ara-C pattern was similar to that observed for all 56 subjects. In these leukemic patients, who were treated with combinations of ara-C plus other conventional agents, a tendency toward a positive response (complete response + partial response) was found for those showing low ara-U/ara-C ratios (slow deaminators). The phenotypic effect of deamination in acute leukemia needs to be evaluated prospectively. PMID- 1600593 TI - Activity of two platinum-linked phosphonic acids against autochthonous rat colorectal cancer as well as in two human colon-cancer cell lines. AB - Two new platinum-containing phosphonate compounds, cis diammine[nitrilotris(methylphosphonato)(2-)- O1,N1]platinum(II) (AMDP) and cis cyclohexane-1,2-diamine[nitrilotris(methylphosphonato) (2-)-O1,N1]platinum(II) (DADP) were investigated in acetoxy-methyl-methylnitrosamine-induced autochthonous colorectal rat adenocarcinoma in vivo as well as in two human colon cancer cell lines (SW707 and SW948) in vitro. In the in vivo model, the two compounds were given i.v. at doses of 8 and 13 mg/kg as well as p.o. at 16 and 26 mg/kg twice a week for 10 weeks, respectively. AMDP produced more intensive toxicity at both doses but showed higher antitumour activity only following i.v. administration. On the other hand, DADP caused significant tumour-growth inhibition after both modes of application, but as it produced only low toxicity, its use should be favoured. The in vitro assays were performed using two cell lines derived from human colorectal adenocarcinomas. According to the microculture tetrazolium test (MTT) AMDP (IC50, 34 and 59 microM in SW707 and SW948, respectively) was more effective than DADP (IC50, 412 and 660 microM in SW707 and SW948, respectively) in inhibiting cell growth. Based on cell counts AMDP (IC50, 8 and 11 microM in SW707 and SW948, respectively) and DADP (IC50, 266 and 285 microM in SW707 and SW948, respectively) showed more intensive antiproliferative efficacy as determined by the Coulter Counter method vs the MTT assay. The promising activities of these new platinum-linked phosphonic acids in autochthonous rat colorectal carcinoma and in human colorectal cancer cell lines warrant further investigations of compounds of this class to elucidate their role in the treatment of colorectal cancer. PMID- 1600594 TI - Effect of a low-protein diet on doxorubicin pharmacokinetics in the rabbit. AB - Malnutrition involving protein deficiency, which commonly occurs in cancer patients receiving anthracycline treatment, is considered to be a risk factor for the development of cardiotoxicity. Protein deficiency has been shown to impair the metabolism of drugs such as theophylline and acetaminophen. If protein deficiency also impairs anthracycline metabolism, it could explain at least in part the enhanced anthracycline toxicity associated with malnutrition. We tested this idea by determining the effect of a low-protein, isocaloric diet on doxorubicin pharmacokinetics in rabbits. The animals were randomized into two groups for 8-12 weeks. Rabbits in group 1 received a low-protein (5%), isocaloric diet, whereas those in group 2 received a normal-protein (15%) diet. Both groups (group 1, n = 15; group 2, n = 14) were given 5 mg/kg doxorubicin by i.v. bolus. After doxorubicin injection, blood samples were obtained over the next 52 h for the measurement of doxorubicin and doxorubicinol plasma concentrations by high performance liquid chromatography (HPLC) with fluorometric detection. The low protein diet significantly decreased doxorubicin clearance (48 +/- 3 vs 59 +/- 4 ml min-1 kg-1; P less than 0.05), prolonged the terminal elimination half-life (28 +/- 2 vs 22 +/- 2 h; P less than 0.05), and increased the area under the plasma concentration/time curve extrapolated to infinity (1722 +/- 122 vs 1405 +/ 71 ng h ml-1; P less than 0.05) as compared with the values determined for rabbits fed the standard rabbit chow (15% protein). The volume of distribution for doxorubicin was not altered by the low-protein diet. In addition, in rabbits fed the the low-protein diet, the terminal elimination half-life of the alcohol metabolite, doxorubicinol was prolonged (52 +/- 5 vs 40 +/- 2 h; P less than 0.05). Thus, a low-protein diet causes a reduction in the ability of rabbits to eliminate doxorubicin and possibly its alcohol metabolite doxorubicinol. If a similar alteration in anthracycline pharmacokinetics occurs in malnourished cancer patients, this phenomenon may contribute to their increased risk of developing cardiotoxicity associated with anthracycline therapy. PMID- 1600595 TI - Gut protection by cyclophosphamide "priming" in patients receiving high-dose melphalan--effect of drug scheduling. AB - A "priming" injection of cyclophosphamide (400 mg/m2 given i.v. on day -7) has been shown to reduce intestinal permeability and thus gut toxicity in patients receiving high-dose melphalan. To determine the optimal timing for this injection, patients receiving 200 mg/m2 melphalan with an autologous bone marrow transplant were randomly assigned to receive cyclophosphamide at 5, 7 or 9 days before the melphalan. The median percentage of [51Cr]-ethylenediaminetetraacetic acid excretion was similar (9.1% vs 7.1% vs 7.7%, respectively), with equivalent duration of WHO grade 2-4 mucositis and diarrhoea being recorded for each group. Thus, the timing of the cyclophosphamide prime is not critical, and the priming injection may be given between 5 and 9 days prior to high-dose melphalan. PMID- 1600596 TI - Synergistic interaction of cyclosporin A and verapamil on vincristine and daunorubicin resistance in multidrug-resistant human leukemia cells in vitro. AB - We studied the effects of cyclosporin A and verapamil on the modulation of vincristine and daunorubicin resistance in a multidrug-resistant subline of human T-cell acute lymphatic leukemia GM3639. Our results show that cyclosporin A is more effective than verapamil as a modulator of the high degree of primary vincristine resistance and the low degree of daunorubicin cross-resistance expressed by this cell line. Isobologram analysis revealed that the combined modulators act synergistically in correcting both vincristine and daunorubicin resistance. PMID- 1600597 TI - A phase II trial of continuous-infusion 6-mercaptopurine for childhood leukemia. AB - A phase II pediatric trial of a continuous intravenous infusion of 6 mercaptopurine (6MP) in patients with refractory leukemia was performed. The dosing schedule, 50 mg m-2 h-1 for 48 h, was based on the results of a previous phase I trial of this approach. Among the 40 children treated for acute lymphoblastic leukemia (ALL), all of whom had received prior therapy with oral 6MP, 1 complete and 1 partial response were achieved. No response was observed in 17 patients with refractory acute nonlymphocytic leukemia (ANLL). Reversible hepatotoxicity, the primary dose-limiting toxicity, was observed in approximately 50% of cases. Mucositis was encountered infrequently and was usually not severe. 6MP given on the present continuous intravenous infusion schedule overcomes the limited and variable bioavailability of oral 6MP but shows limited activity as induction agent in children with recurrent ALL. PMID- 1600598 TI - Pilot study of escalating doses of carboplatin and cyclophosphamide in patients with advanced cancer. AB - In all, 18 patients with histologically proven advanced cancer received 400 mg/m2 carboplatin (CBDCA) plus 800 mg/m2 cyclophosphamide (level 1), and 14 others received 550 mg/m2 CBDCA plus 1100 mg/m2 cyclophosphamide (level 2). A maximum of six cycles was given if a response occurred. The dose-limiting toxicity was myelosuppression, with neutropenia being more marked than thrombocytopenia. At level 2, patients experiencing a febrile-neutropenic event showed a mean 24-h urinary creatinine clearance value of 1.1 ml/s (95% confidence limits 0.8-1.4 ml/s), whereas in those who remained afebrile it was 1.7 ml/s (95% confidence limits, 1.3-2.0 ml/s). This difference was significant (P less than 0.01). Other toxicities were only mild. Creatinine clearance is a predictor of febrile episodes after treatment with high doses of CBDCA and cyclophosphamide. We are now conducting a study using human granulocyte colony-stimulating factor to reduce the incidence of neutropenia with escalating doses of these drugs in an attempt to prevent febrile events. PMID- 1600599 TI - In vivo distribution of [11C]-busulfan in cynomolgus monkey and in the brain of a human patient. AB - The in vivo distribution of the antileukemic agent busulfan labeled with the positron-emitting radionuclide carbon 11 was investigated in cynomolgus monkeys and in a human patient using positron emission tomography. After i.v. injection of the radiotracer, its regional uptake was monitored for about 1 h in the monkey's body and, in a separate experiment, in the monkey's brain. The concentration of radioactivity in the liver, which showed the highest levels of all the organs scanned, increased throughout the experiment and was 9-fold that in the brain at the end of the experiment. [11C]-Busulfan rapidly crossed the blood-brain barrier. The radioactivity peaked in both the cortex and the white matter showing a ratio of 1.25, at 3 min but declined quickly to yield a ratio of approximately 1 after 30 min. In the human brain, radioactivity in the cerebellum, cortex, and white matter reached a maximum within 5 min showing a cortex:white matter ratio of 1.6. The activity in the cortex declined to yield a ratio of 1 within 30 min. Of the delivered dose, 20% penetrated into the brain. PMID- 1600600 TI - Toxicity and metabolism of 3'-deoxyadenosine N1-oxide in mice and Ehrlich ascites tumor cells. AB - The toxic effect of 3'-deoxyadenosine N1-oxide (3'-dANO) on mice, on their different organs, and on Ehrlich ascites tumor cells was studied. In both healthy and tumour-bearing animals, the lethal dose for 10% of the mice receiving i.p. injections (LD10) of 3'-dANO was estimated to be about 300 mg/kg x 4 days in one mouse strain (Theiller). In another mouse strain (NMRI), we obtained a markedly higher LD10 value (675 mg/kg x 5 days). At nonlethal doses (250 mg/kg x 4 days), we observed reversible neurological symptoms on days 4-12 after treatment, but no macroscopical or microscopical changes was detected in the brain, heart, thymus, lung, lymph node, spleen, liver, kidney, bone marrow, or gastrointestinal tract. At doses of 450 mg/kg x 4 days, severe neurological symptoms were observed, and atony of the gastrointestinal canal and damage to the kidney and liver were registered. Even at doses that were lethal to the mice, no histopathological change was observed in the bone marrow or in the gastrointestinal canal. Pharmacokinetics studies showed that after the i.p. injection of 3'-dANO, the maximal plasma concentration was reached after 10 min, after which it declined showing a half-life of about 40 min. A transient accumulation of 3' deoxyadenosine triphosphate (3'-dATP) was observed within 24 h in the liver and kidney, with the maximal concentration being reached after about 2-3 h. 3'-dANO was excreted partly as the unchanged substance and partly as the metabolite 3' deoxyinosine within 24 h. Flow-cytometric DNA analysis of Ehrlich tumor cells treated either in vitro or in vivo with 3'-dANO revealed no therapy-induced change in the cell-cycle perturbations, which indicates that cells were randomly killed during all phases of the cycle. PMID- 1600601 TI - Reducing doxorubicin cardiotoxicity in the rat using deferred treatment with ADR 529. AB - The purpose of this study was to evaluate the optimal timing of ADR-529 administration to protect rats treated with doxorubicin (DXR) against drug induced cardiotoxicity. Complete electrocardiographic monitoring (QRS complex, S alpha T segment and T wave) and the histopathological analysis of cardiac tissue were used to assess the degree of heart damage produced in female rats treated with ten i.v. doses of 1 mg/kg DXR over a period of 15 weeks; body-weight increase and survival were also analyzed to evaluate the toxicity of treatments. Cardiac alterations induced by DXR were compared with those occurring in animals receiving 20 mg/kg i.v. ADR-529 at 30 min prior to DXR administration, starting at the first, third, or sixth DXR dose and given until the end of the study (15th week). Rats treated with DXR were severely cardiomyopathic, showing progressive and irreversible ECG alterations (QRS-complex and S alpha T-segment widening and T-wave flattening) and marked degeneration of the myocardium (myocyte vacuolation, myofibrillar loss, and endomyocardial fibrosis). The most effective cardiac protection was provided by the administration of ADR-529 beginning with the first or third DXR dose. Delaying treatment with ADR-529 until the sixth DXR dose resulted in a significant reduction in its therapeutic action on heart damage. A significant difference in body-weight increase and survival was observed between the treatment groups: ADR-529 injected prior to the first DXR dose significantly protected animals from DXR toxicity, but this schedule was significantly more toxic than the administration of ADR-529 beginning with the third or sixth DXR dose. Taking into account the degree of cardiac protection and the toxicity of combination treatments, the results of the present study demonstrate the superiority of ADR-529 given prior to the third DXR dose over the other schedules tested. This finding suggests that significant protection against DXR-induced chronic cardiotoxicity in the rat can be obtained using deferred treatment with ADR-529. PMID- 1600603 TI - Interpretation of labeling indices in the presence of cell death. AB - A simple method is presented for the analysis of data on labeling indices in populations of cells undergoing division and apoptosis. The method is applicable to continuous, osmotic pump labeling experiments, and provides estimates of cell division rates. Cell replication kinetics play an important role in carcinogenesis, and the interpretation presented here should help in the incorporation of data on labeling indices into quantitative models for cancer risk assessment. PMID- 1600602 TI - Carcinogenic tobacco-specific nitrosamines are present at unusually high levels in the saliva of oral snuff users in Sudan. AB - Exposure to tobacco-specific nitrosamines (TSNA) has been measured in the saliva of 12 users of Sudanese oral snuff (toombak). Using GC coupled to thermal energy analysis, levels of N'-nitrosonornicotine (NNN), N'-nitrosoanatabine (NAT), N' nitrosoanabasine (NAB) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) were measured before, during and after snuff taking. In addition, two TSNA, 4 (methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and 4-(methylnitrosamino)-4-(3 pyridyl)-1-butanol (iso-NNAL), were detected in the saliva of tobacco chewers for the first time and were confirmed by GC-MS. Nine out of 10 subjects had detectable saliva levels of total TSNA before chewing (0.01-1.0 micrograms/ml) and immediately following chewing (0.1-2.6 micrograms/ml). During dipping, TSNA concentrations reached microgram/ml levels; (range; number of subjects positive) NNN: (0.6-2.1; 12/12), NAT (0.06-0.5; 2/12), NAB (0.05-1.9; 12/12), NNK (0.06 6.7; 11/12), NNAL (0.05-3.3; 11/12) and iso-NNAL (0.07-0.4; 8/12). These saliva TSNA levels, which are 10-100 times the levels previously reported, are consistent with recent observations of unusually high TSNA levels in Sudanese toombak. As several of these TSNA have been shown to be carcinogenic in animals and epidemiological studies have associated human snuff use with tumours of the oral cavity, these findings draw attention to a significant potential public health hazard. PMID- 1600604 TI - Contrasting hepatocytic peroxisome proliferation, lipofuscin accumulation and cell turnover for the hepatocarcinogens Wy-14,643 and clofibric acid. AB - Earlier studies indicated that the hepatocarcinogenic activity of two peroxisome proliferators (PP) Wy-14,643 and di(2-ethylhexyl)phthalate (DEHP) correlated to the degree of lipofuscin accumulation and sustained cell replication rather than the level of peroxisome induction. This study extends the comparison of peroxisome proliferation, lipofuscin accumulation and cell replication responses in rats fed (i) clofibric acid at 5000 p.p.m. (CA), a regimen of moderate hepatocarcinogenicity; (ii) Wy-14,643 at 50 p.p.m. (WYLD), a dose of unknown hepatocarcinogenicity; and (iii) Wy-14,643 at 1000 p.p.m. (WYHD), as the highly hepatocarcinogenic regimen. Adult male F344 rats were fed the experimental diets for 1, 2, 5, 11 or 22 weeks. Relative liver weights (% of body weight) were increased in rats fed CA (1.6- to 1.7-fold), WYHD or WYLD (2.0- to 2.7-fold), compared to controls (approximately 3%) at all time points. All rats fed CA, WYHD or WYLD had similar hepatic peroxisome proliferation at all time points with large elevations in peroxisomal enzyme activities and number, size and mean volume of peroxisomes. In contrast, hepatocytic lipofuscin accumulation differed between treatments, with a decreasing order of accumulation observed in WYHD greater than WYLD approximately equal to CA greater than controls. Replicative DNA synthesis (as assessed by nuclear labeling index, LI) in nonlesion hepatocytes was markedly elevated at 1 week by both WYHD and WYLD (45- and 40 fold over controls respectively) while CA induced a 10-fold response over controls (control LI less than or equal to 1%). From week 2 to week 22 the hepatocytic LI was sustained in WYHD and WYLD rats (8- and 4-fold over controls respectively) but not in CA-rats, as compared to controls. In contrast to the cell replication response, apoptosis was elevated only in WYHD at 22 weeks. Collectively, this study supports the conclusion that neither hepatomegaly nor peroxisome proliferation are accurate predictors of carcinogenic activity for PP. Further, these results suggest that if lipofuscin accumulation or sustained cell turnover are indicators of PP-induced carcinogenesis, then WYLD should be at least as carcinogenic as CA. The moderate carcinogenic activity of CA also suggests that additional factor(s) may be necessary besides lipofuscin accumulation and sustained cell replication to determine the ultimate carcinogenic activity of PP. PMID- 1600605 TI - Inhibition of colon carcinogenesis by prostaglandin synthesis inhibitors and related compounds. AB - The inhibitory effect of 40 and 80% maximum tolerated dose (MTD) levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid on colon carcinogenesis was investigated in male F344 rats. The MTD levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid as determined in male F344 rats were 500, 500, 250 and 3000 p.p.m. respectively. At 5 weeks of age, groups of male F344 rats were fed the control (AIN-76A) diet and 40 and 80% MTD levels of each test agent in AIN-76A diet. At 7 weeks of age, all animals except the vehicle (saline) treated controls received azoxymethane (AOM) at a dose rate of 15 mg/kg body wt, once weekly for 2 weeks. All animals were necropsied 50 weeks after the second AOM injection and colon tumor incidences were compared among the groups fed the control diet and chemopreventive agents. Animals fed 400 (80% MTD) and 200 p.p.m. (40% MTD) of piroxicam, 400 p.p.m. (80% MTD) of ibuprofen and 200 p.p.m. (80% MTD) of ketoprofen showed a significant inhibition of colon tumorigenesis as compared to those fed the control diet. Results analyzed by the linear regression method suggested a dose-dependent inhibition of colon carcinogenesis with increasing levels of piroxicam or ibuprofen. In contrast, glycyrrhetinic acid had no measurable chemopreventive effect on colon carcinogenesis. PMID- 1600606 TI - Determination of human exposure to the dietary carcinogen 3-amino-1, 4-dimethyl 5H-pyrido[4,3-b]indole (Trp-P-1) from hemoglobin adduct: the relationship to DNA adducts. AB - A quantitative method for estimation of the exposure of the food-borne carcinogen, 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), was developed by the analysis of its hemoglobin binding in rats. This method was then applied to show the presence of Trp-P-1-hemoglobin adducts in human blood. In rat experiments, 0.2 and 0.07% of the administered [14C]Trp-P-1 formed stable covalent adducts with blood hemoglobin and plasma proteins respectively. Subsequent strong acidic treatment (6 N HCl, 110 degrees C, 24 h) of the Trp-P-1 hemoglobin adducts cleaved peptide bonds of globin, and yielded mainly three derivatives of Trp-P-1. One of them (TPHB) represented approximately 50% of the total Trp-P-1-hemoglobin adducts and was suitable for detection through its strong fluorescence. TPHB was used as a surrogate marker of the Trp-P-1 hemoglobin adducts. Linear dose dependency of Trp-P-1 binding to liver DNA and hemoglobin in rats was confirmed by 32P-postlabeling analysis and TPHB assay. The absence of Trp-P-1-DNA adducts and TPHB in nontreated rats was also confirmed. Using TPHB as a tool for human dosimetry of Trp-P-1, human blood samples from four healthy individuals were examined. TPHB was detected in all samples ranging from 0.23 to 4.33 pmol/g hemoglobin. These results suggest human exposure to Trp P-1, probably from cooked foods or cigarette smoke, and its possible relationship to human carcinogenesis. PMID- 1600607 TI - Aflatoxin B1--DNA adduct formation in rat liver following exposure by aerosol inhalation. AB - There is growing concern that human exposure to respirable grain dust contaminated with aflatoxin B1 (AFB1), a potent hepatocarcinogen, may be a risk factor for a number of human diseases. The objective of this study was to determine if liver DNA adduct formation occurs in rats following either intratracheal injection or nose-only aerosol inhalation exposure to AFB1. Male Fischer 344 rats were exposed by both routes of administration, and in preliminary data using intratracheal instillation, up to 2% of the administered dose became bound to liver DNA. In the nose-only aerosol inhalation experiments, rats were exposed for up to 120 min. Immediately after exposure, four animals were killed at each time point and their livers removed, DNA isolated and purified and analyzed for aflatoxin-DNA adducts by HPLC. A linear dose-response relationship was observed with a correlation coefficient of 0.96 between increasing length of exposure, and the amount of aflatoxin-N7-guanine adducts formed per mg DNA, the mean values and standard errors were 4.2 +/- 0.18, 15.3 +/ 4.3, 21.6 +/- 2.8 and 56.8 +/- 4.6 pmol aflatoxin-DNA adducts per mg DNA for the 20, 40, 60 and 120 min exposures respectively. The amounts of aflatoxin-DNA adducts formed were statistically significantly different (P less than 0.01) among the treated groups. These results indicate that aerosol inhalation is an effective route of exposure to AFB1 in rats that results in genotoxic damage in the liver. PMID- 1600608 TI - Relationship between the debrisoquine hydroxylase polymorphism and cancer susceptibility. AB - There have been a series of reports on the association of a genetic polymorphism at the cytochrome P450 CYP2D6 gene locus with cancer susceptibility. Many of these reports have remained contradictory either because of small numbers of patients studied or because of the limitations and controversy surrounding the pharmacokinetic assay used to identify affected individuals (poor metabolizers; PMs). We have recently developed a DNA-based assay that will allow the unequivocal identification of poor metabolizers and have applied this to the study of 1635 patients with different forms of cancer. Out of 361 lung cancer patients studied no statistically significant change in the proportion of PMs relative to controls was found. However, a significant increase in the proportion of poor metabolizers or heterozygotes was seen in leukaemia, bladder cancer and melanoma patients. This could be explained by a role for CYP2D6 in carcinogen detoxification or by linkage to another cancer-causing gene. PMID- 1600609 TI - Relationship between calculus formation and carcinogenesis in the urinary bladder of rats administered the non-genotoxic agents thymine or melamine. AB - Urinary bladder lesions induced by administration of thymine or melamine were investigated in male F344 rats. Animals, 6 weeks old at the beginning of the experiment, received either 3.0 or 1.0% thymine or 3.0, 1.0 or 0.3% melamine in the diet for 36 weeks followed by a 4 week period without chemicals, the total observation time being 40 weeks. Carcinomas of the urinary bladder were observed in 1/20 (5%) rats in each of the 3.0% thymine and 1.0% melamine groups, and in 15/19 (79%) animals given the 3.0% melamine treatment. Papillomas were induced in 9/20 (45%), 12/19 (63%) and 1/20 (5%) among rats receiving the 3.0% thymine, 3.0% and 1.0% melamine treatments respectively. Exploratory laparotomy at the end of week 36 revealed calculus formation in 9/10 (90%), 10/10 (100%) and 7/10 (70%) rats in these groups. In the ureter of the 3.0% melamine treated group, a carcinoma and papillomas were induced in 1/19 (5%) and 3/19 (16%) animals respectively. However, no tumors were observed in the renal pelvis in any of the other treated groups. Thus, administration of 3.0% thymine in the diet results in calculus formation in the urinary bladder of F344 rats, and is associated with development of tumors. It was also confirmed that a 3.0% dose level of melamine in the diet induces tumors in both the urinary bladder and the ureter. PMID- 1600610 TI - Inhibition of intercellular communication in human keratinocytes by fractionated asphalt fume condensates. AB - Asphalt fume condensate (AFC) and chromatographically separated fractions have been shown to cause cancer in mouse skin. The levels of known carcinogenic initiators in these complex mixtures, however, are considered too low to account for their carcinogenic potency. It has been proposed that AFC may contain co carcinogenic or tumor-promoting agents in addition to carcinogenic initiators. Modulation of gap junctional intercellular communication (GJIC) has been implicated as an important effect of tumor promoters. In this study, we examined the effect of five chromatographically generated fractions of AFC on GJIC in cultured human epidermal keratinocytes (HEK). HEK cells were exposed overnight to medium containing DMSO extracts of AFC fractions. GJIC was evaluated by dye coupling of microinjected Lucifer Yellow CH. All AFC fractions produced a concentration-dependent inhibition of GJIC. The apparent potency of each fraction correlated with its relative polarity based on HPLC elution characteristics. Cells with reduced GJIC as a result of AFC fraction exposure were found to exclude propidium iodide, suggesting that inhibition of GJIC occurred in the absence of cell killing. However, significantly reduced culture DNA content was found following the overnight exposure to the highest concentrations of AFC fractions C, D and E. PMID- 1600611 TI - Monoclonal antibodies and rabbit antisera recognizing 4-aminobiphenyl--DNA adducts and application to immunoaffinity chromatography. AB - Monoclonal antibodies and rabbit antisera were produced that recognized 4 aminobiphenyl, its major DNA adducts and other metabolites. The antigens used to raise these antibodies were synthesized by coupling the aromatic amine to protein through a diazotization reaction. The goal of this immunization strategy was to induce antibodies that also cross-reacted with most 4-aminobiphenyl-derived metabolites. A total of 20 mice and four rabbits were immunized and every animal produced a strong immune response for 4-aminobiphenyl and its derivatives. Two IgG1 monoclonal antibodies, 3D6 and 2E11, were isolated from two different mouse spleen cell fusions. One of the monoclonal antibodies, 3D6, had a high recognition for the three major 4-aminobiphenyl-DNA adducts: N-(deoxyguanosine-8 yl)-4-aminobiphenyl, N-(deoxyadenosin-8-yl)-4-aminobiphenyl and N-(deoxyguanosine N2-yl)-4-aminobiphenyl, with affinity constants between 2 and 4 x 10(9) l/mol. In addition, one of the rabbit anti-sera had an affinity constant for the DNA adducts of 2.1 x 10(9) l/mole. Thus, the strategy to use a diazotization coupling reaction was successful at producing high-affinity aminobiphenyl-DNA adduct specific antibodies. Preparative immunoaffinity resins were made for each monoclonal antibody. These resins quantitatively bound 500 ng each [3H]N-acetyl aminobiphenyl, [3H]N-aminobiphenyl and [3H]N-(deoxyguanosine-8-yl)-4 aminobiphenyl. Preliminary experiments were performed to test the applicability of the preparative monoclonal antibody immunoaffinity column to isolate [3H]4 aminobiphenyl-derived metabolites in dosed rat and dog urine. About 70% of the radioactivity in rat or dog urine could be bound to the immunoaffinity columns. The combined immunoaffinity column/HPLC analysis of the dog urine led to the identification of a novel urinary metabolite, N-formyl-aminobiphenyl. HPLC analysis of a rat urine sample tentatively found 4-aminobiphenyl, N-acetyl-4 aminobiphenyl and N-formyl-4-aminobiphenyl by co-chromatography, and these compounds accounted for 20, 6.8 and 6.5% of the total radioactivity in the chromatogram respectively. Taken together, these data show that these 4 aminobiphenyl-specific monoclonal antibodies can be used in immunoaffinity columns to isolate metabolites and DNA adducts from biological samples. PMID- 1600612 TI - Delayed reproductive death as a dominant phenotype in cell clones surviving X irradiation. AB - Residual damage manifested as reduced cloning efficiency was observed in many of the cloned progeny of Chinese hamster ovary (CHO) cells and human carcinoma SQ 20B cells surviving X-irradiation. This stable phenotype, which we have termed delayed reproductive death, persisted for greater than 50 generations of cell replication post-irradiation. Clones showing this phenotype were aneuploid, and formed colonies with a high proportion of giant cells. By somatic cell hybridization of CHO clones, the delayed reproductive death phenotype was found to be a dominant trait; the cloning efficiency of hybrid clones was persistently depressed, as compared with that of control hybrid cells. These results suggest that delayed reproductive death represents a specific cellular response that may persist in some of the progeny of mammalian cells for long periods after X irradiation. PMID- 1600613 TI - Stereoselective metabolism of (-)-benzo[a]pyrene-7,8-diol by human lung microsomes and peripheral blood lymphocytes: effect of smoking. AB - Benzo[a]pyrene (B[a]P)-tetrols formed after stereoselective cytochrome P450 dependent metabolism from (-)-trans-7,8-dihydroxy-7,8- dihydrobenzo[a]pyrene [(-) B[a]P-7, 8-diol] by lung microsomes (n = 19) and peripheral blood lymphocytes (n = 13) from lung cancer patients were measured, and the effect of smoking explored. B[a]P-tetrols were quantified by an HPLC/fluorescence assay with a detection limit of approximately 300 attomol, after incubation with peripheral blood lymphocytes or microsomes from lung cancer patients who were current cigarette smokers, ex-smokers and non-smokers. In lymphocytes from these subjects, high, medium and low metabolic activities respectively for (-)-B[a]P 7,8-diol to tetrol conversion were found, but there was no statistically significant difference between smokers, ex-smokers and non-smokers. When the B[a]P-tetrol formation by human lung microsomes was measured, recent smokers had 4- to 7-fold higher (P = 0.04) metabolic activity than ex-smokers and non smokers. The mean lung microsomal arylhydrocarbon hydroxylase (AHH) activity was three times higher in smokers than in non-smokers and was undetectable in ex smokers. AHH activity was correlated with tetrol formation in the same lung microsomal samples (r = 0.62, P less than 0.01 in smokers; and r = 0.67, P less than 0.01 in all subjects). When subjects were grouped according to smoking habits, however, no correlation was detected between mean tetrol formation by lung microsomes and that of lymphocytes. Thus, lymphocytes cannot serve as a surrogate for lung microsomes concerning the pulmonary metabolism of (-)-B[a]P 7,8-diol. The much higher B[a]P-tetrol formation observed in lung microsomes from smokers is in accord with a reported higher pulmonary AHH activity, cytochrome P450IA level, and CYP1A1 gene expression in recent tobacco smokers. PMID- 1600614 TI - Foci of altered hepatocytes induced in embryonal turkey liver. AB - Fertilized turkey eggs were injected with N-nitrosomopholine (1-10 mg/egg) or urethane (0.1-10 mg/egg) prior to or during the first hours of incubation. Four days prior to hatching, the experiments were terminated and the livers of the embryos removed. The hepatocarcinogens induced focally arranged hepatocytes with morphological and metabolic changes that were similar to preneoplastic foci observed in rodent studies in vivo. Foci with enlarged cells and excessive storage of glycogen as well as basophilic foci with small cells, low in glycogen content and with frequent mitotic figures were found. The in ovo transformation of embryonal hepatocytes may be a promising rapid model of hepatocarcinogenesis. PMID- 1600615 TI - Inhibitory effect of topical application of a green tea polyphenol fraction on tumor initiation and promotion in mouse skin. AB - A green tea polyphenol fraction was evaluated for its ability to inhibit tumor initiation by polycyclic aromatic hydrocarbons and tumor promotion by a phorbol ester in the skin of CD-1 mice. Topical application of the green tea polyphenol fraction inhibited benzo[a]pyrene- and 7,12-dimethylbenz[a]-anthracene-induced tumor initiation as well as 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced tumor promotion. Topical application of the green tea polyphenol fraction also inhibited TPA-induced inflammation, ornithine decarboxylase activity, hyperplasia and hydrogen peroxide formation. Studies with individual polyphenolic compounds in green tea indicated that topical application of (-)-epigallocatechin gallate, (-)-epigallocatechin and (-)-epicatechin gallate inhibited TPA-induced inflammation in mouse epidermis. PMID- 1600616 TI - Acetyl transferase-mediated metabolic activation of N-hydroxy-4-aminobiphenyl by human uroepithelial cells. AB - Metabolism and nucleic acid binding of N-hydroxy-4-aminobiphenyl (N-OH-ABP), a proximate carcinogenic metabolite of the human bladder carcinogen 4-aminobiphenyl (ABP), was investigated using cultured normal human uroepithelial cells (HUC). HPLC and TLC of the ethyl acetate extract of the media from cultured HUC after 4 h exposure to N-OH-ABP revealed the formation of two major metabolites, ABP and 4 acetylaminobiphenyl (AABP), suggesting the presence of N-acetyl transferase(s) in HUC. This was further confirmed by the formation of AABP, during the incubation of ABP with acetyl coenzyme A (AcCoA) and HUC cytosol. To test whether these enzymes also catalyze the AcCoA-dependent O-acetylation, we examined the metabolic activation of N-OH-ABP using cytosolic preparations. Cytosol from HUC catalyzed AcCoA-dependent binding of [3H]N-OH-ABP to RNA; the amount of binding was 757 pmol/mg RNA/mg protein. Binding with DNA was quantitatively similar to RNA. HPLC and TLC analyses of the enzymatic hydrolysate of [3H]N-OH-ABP-bound DNA revealed the major adduct to be N-(deoxyguanosine-8-yl)-4-aminobiphenyl, based on mobility of the radioactivity in comparison with the authentic synthetic standard. 32P-Post-labeling analysis of the DNA from the cytosol-mediated binding of N-OH-ABP revealed four radioactive spots. In contrast, post-labeling analysis of the DNA from intact HUC exposed to N-OH-ABP showed five adducts, including two of the adducts observed with HUC cytosols, suggesting the possible involvement of additional activation pathway(s) in intact HUC. These results suggest that bioactivation of N-OH-ABP could occur within the HUC, the target organ for ABP, and that cytosolic acetyl transferase(s) may play a critical role in susceptibility to arylamine-induced bladder carcinogenesis. PMID- 1600617 TI - Altered expression of a mouse epidermal cytoskeletal protein is a sensitive marker for proliferation induced by tumor promoters. AB - Treatment of mouse skin with tumor promoters such as 12-O-tetradecanoylphorbol-13 acetate (TPA), 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) or 8-methoxypsoralen and ultraviolet light (PUVA) caused a marked decrease in the expression of p48, an acidic epidermal protein. This protein was specifically identified in mouse epidermis and confluent PAM 212 mouse keratinocytes in culture. Extraction of p48 required strong denaturing conditions (greater than 8 M urea) as well as a reducing agent, indicating that this protein was associated with the cytoskeleton. Positive immunoblot staining of p48 with antikeratin monoclonal antibodies following two-dimensional polyacrylamide gel electrophoresis suggested that this protein may be related to the acidic keratins. The sensitivity of this protein to topically applied mitogens and tumor promoters implies that p48 expression is important in normal epidermal cell growth and differentiation. PMID- 1600618 TI - Molecular dosimetry of DNA adducts in C3H mice treated with bisphenol A diglycidylether. AB - The formation of a glycidaldehyde-DNA adduct in skin of C3H mice treated with [14C]bisphenol A diglycidylether has been previously reported and it was assumed that the modification occurred on guanine residues. We were interested in elucidating the structure of this glycidaldehyde-DNA adduct by using a non radioactive approach. Male C3H mice were treated with a single topical dose of 2 mg bisphenol A diglycidylether in acetone for 48, 96 or 192 h. An additional two mice were treated with 2 mg glycidaldehyde in acetone for 24 h. Epidermal DNA was isolated and enzymatically digested to nucleoside-3'-monophosphates. Aliquots of the DNA hydrolysates were separated on HPLC using a reverse-phase column with a potassium dihydrogen phosphate/methanol gradient. Fluorescence analysis of the eluent indicated the presence of a fluorescent DNA adduct, which was identified as hydroxymethylethenodeoxyadenosine-3'-monophosphate by comparison with a synthetic reference standard. Amounts of adducts were determined by fluorescence measurements using a calibration curve obtained with the authentic adduct standard. Irrespective of duration of exposure, all DNA hydrolysates of treated mice contained similar amounts of the deoxyadenosine adduct. The alkylation frequency was 0.1-0.8 and 166 adducts/10(6) normal nucleotides for the treatment with bisphenol A diglycidylether and glycidaldehyde respectively. The limit of detection using 500 micrograms DNA samples for analysis was approximately 0.03 adducts/10(6) normal nucleotides. PMID- 1600619 TI - Birth and death/differentiation rates of papillomas in mouse skin. AB - A simple one-stage model for the formation of papillomas is used to evaluate data from a series of initiation/promotion/stop-promotion experiments performed on NMRI mice. These experiments used a single application of 100 nmol 7,12 dimethylbenz[a]anthracene followed by twice weekly applications of 5 nmol 12-O tetradecanoylphorbol-13-acetate. It is shown that, on the basis of this model, the data considered here provide no evidence for a growth advantage of initiated cells versus normal cells. Although model estimates always have to be treated with utmost caution, they can at least be interpreted in a qualitative way. In consequence, it has to be concluded either that the mechanism upon which the model is based fails to describe properly the growth behaviour of initiated cells, or that initiated cells do not possess a growth advantage over normal cells, even in the presence of a promoter. PMID- 1600620 TI - Participation of rat liver cytochrome P450 2E1 in the activation of N nitrosodimethylamine and N-nitrosodiethylamine to products genotoxic in an acetyltransferase-overexpressing Salmonella typhimurium strain (NM2009). AB - The possible roles of cytochrome P450 (P450) enzymes in the metabolic activation of N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) by rat liver microsomes have been examined in a system containing the bacterial tester strain Salmonella typhimurium NM2009, a newly developed strain showing high O acetyltransfer activities. The DNA-damaging activity could be determined by measuring expression of the umu gene in a plasmid containing the fused umuC-lacZ gene construct in the bacteria. The following lines of evidence support the view that both NDMA and NDEA are principally oxidized to reactive products by P450 2E1 in rat liver microsomes. First, NDMA and NDEA were activated by rat liver microsomes in a protein- and substrate-dependent manner and the former chemical was more active than the latter; both activities were induced in rats treated with P450 2E1 inducers such as ethanol, acetone and isoniazid and by starvation. Second, activation of NDMA and NDEA were both inhibited significantly by antibodies raised against rat P450 2E1 and by P450 2E1 inhibitors such as diethyldithiocarbamate and 4-methylpyrazole in rat liver microsomes. Finally, in reconstituted monooxygenase systems containing purified rat P450 enzymes, P450 2E1 gave the highest rates of the activation of both NDMA and NDEA; the addition of rabbit cytochrome b5 to the system caused about a 1.5-fold increase in both reactions. In separate experiments we also found that N nitrosomethylacethoxymethylamine, a compound that reacts with DNA after ester cleavage, is more genotoxic in S.typhimurium NM2009 than in S.typhimurium NM2000, a strain that is defective in O-acetyltransferase activity. Part of the pathway involved in the activation of nitrosamines is suggested to be acetylation of alkyldiazohydroxides formed by P450 or acetylesterase, because the genotoxic activity of N-nitrosomethylacethoxymethylamine in S.typhimurium NM2009 could be inhibited by the O-acetyltransferase inhibitor pentachlorophenol. These results indicate that NDMA and NDEA are oxidized to gentoxoic products by rat liver microsomes and that a P450 2E1 enzyme plays a major role in the activation of these two potent carcinogens. The activation pathway of N-nitrosodialkylamines through acetylation by O-acetyltransferase has been proposed. This simple bacterial system for measuring genotoxicity should facilitate studies on the activation of N-nitroso alkylamines. PMID- 1600621 TI - Polycyclic aromatic hydrocarbon--DNA adducts in white blood cells from lung cancer patients: no correlation with adduct levels in lung. AB - Smokers of cigarettes are exposed to a number of carcinogens, including polycyclic aromatic hydrocarbons (PAHs), and are at a high risk for lung cancer. PAHs exert their carcinogenic activity after metabolic activation to reactive intermediates that can damage DNA through adduct formation. Measuring DNA adducts in peripheral white blood cells (WBC) could serve as a means of monitoring human exposure to genotoxic agents and subsequently risk assessment. In this study, DNA from WBC obtained from 39 lung cancer patients was examined for PAH-DNA adducts both in an ELISA using a polyclonal antibody against benzo[a]pyrene 7,8-diol-9,10 epoxide (BPDE)-DNA and the 32P-post-labeling technique. The ELISA results showed BPDE-DNA antigenicity in WBC DNA from 12/38 (32%) patients and adduct levels ranged from 1.5 to greater than 150 adducts in 10(8) nucleotides. The autoradiographs of chromatograms of 32P-post-labeled digests of WBC DNA from the 38 patients showed a variety of adduct spots; relative adduct labeling (RAL) values ranged from 0.3 to 407 adducts in 10(8) nucleotides. In 18 of the 38 (47%) persons an adduct spot was detected that co-chromatographed with the major BPDE DNA adduct (BPDE-dG); RAL values ranged from 0.03 to 382 adducts in 10(8) nucleotides. Correlations were not significant between the adduct levels in WBC and smoking habits, age or sex. From 20 patients of the same group lung tissue was collected at surgery and examined for PAH-DNA adducts by ELISA and 32P-post labeling assay. No significant correlation was found between DNA adduct levels in blood and lung. This finding stresses the limitations of the use of WBC as a surrogate for adduct levels in the target organ. PMID- 1600622 TI - Effect of the chemopreventive agents piroxicam and D,L-alpha difluoromethylornithine on intermediate biomarkers of colon carcinogenesis. AB - Our previous studies have shown that dietary piroxicam, a non-steroidal anti inflammatory drug (NSAID), and D,L-alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase (ODC) inhibitor, act as potential chemopreventive agents in inhibiting azoxymethane (AOM)-induced colon carcinogenesis in male F344 rats. The present study was designed to determine the effect of these chemopreventive agents on intermediate biomarkers, namely colonic epithelial cell proliferation and levels of prostaglandins, which can be used as effective predictors of colon cancer. Starting at 6 weeks of age, groups of animals were fed the control diet and experimental diets containing piroxicam or DFMO. At 7 weeks of age, all animals, except the vehicle controls, were injected s.c. with AOM at a dose level of 15 mg/kg body wt/week for 4 weeks. Vehicle controls received an equal volume of normal saline. Groups of animals were then killed at the end of last AOM or saline injection (baseline) and at week 4, 16, 24 and 32 following the last AOM or saline treatment. Animals intended for cell proliferation study were injected with bromodeoxyuridine (BrdU) at a dose level of 20 mg/kg body wt 1 h prior to being killed. The rate of colonic cell proliferation at all time points was assessed immunohistochemically using anti-BrdU. The levels of colonic mucosal prostaglandins were estimated by radioimmunoassay. The results indicate that carcinogen treatment increased the colonic cell proliferation measured as the crypt labeling index in proximal and distal colons and the concentrations of colonic prostaglandin E2 (PGE2) and 6-keto PGF1 alpha. The data demonstrate that DFMO significantly inhibited the AOM-induced labeling index in the distal and proximal colon at all time points, whereas piroxicam slightly decreased the labeling index. On the other hand, piroxicam exerted a pronounced inhibitory effect on the levels of both PGE2 and 6-keto PGF1 alpha. DFMO suppressed the colonic PGE2 levels to a lesser degree than piroxicam. The results demonstrate that DFMO, an inhibitor of ODC, suppresses cell proliferation, whereas piroxicam, a NSAID, inhibits prostaglandins, and emphasize the need to develop agent dependent intermediate biomarker(s) to validate the efficacy of chemopreventive agent(s) in colon carcinogenesis. PMID- 1600623 TI - Developmental potentialities of cells derived from the truncal neural crest in clonal cultures. AB - The developmental potentialities of single truncal neural crest derived cells were analysed in clonal cultures. The clone-forming ability and differentiation potential of crest cells migrating through the somitic mesoderm of 3-day-old embryos (E3) and of non-neuronal cells of dorsal root ganglia taken at E6-14 were compared. Since most of the cells present in the sclerotomal and rostral parts of the somite at E3 become later on incorporated into the spinal ganglia, one can consider that these two cell populations represent the same derivatives of the trunk neural crest at different developmental stages. After 10 days in vitro, the size of clones and their phenotypic composition varied noticeably, revealing a certain heterogeneity in the founder cell populations in terms of developmental potencies. Clones obtained from migrating neural crest cells at E3 were often large (greater than 1000 cells) and many of them contained neuronal and non neuronal cells. Dorsal root ganglion cells produced mostly small clones (less than 100 cells) in which only non-neuronal (i.e. glial) phenotypes were expressed. Therefore, both the capacity for proliferation and the differentiation ability of cloned neural crest derived cells decrease considerably with increasing embryonic age. This is even more striking if these results are compared with those obtained previously in our laboratory with single cells cultures of E2 cephalic neural crest. In the latter case, both clone sizes and cellular diversity within the colonies were much higher than with E3 truncal crest and dorsal root ganglia (DRG) non-neuronal cells. The second result of the present work concerns the differentiation of the dormant autonomic neuronal precursors of the DRG. It has been established previously that the non-neuronal cells of the DRG include adrenergic precursors than can differentiate in mass culture of dissociated DRG cells. We show that these cells never differentiate in clonal cultures but depend upon the cell density of the culture. This suggests that cell to cell interaction between crest derived cells are critical in eliciting the differentiation of the adrenergic phenotype. PMID- 1600624 TI - Distribution of the novel developmentally-regulated protein EAP-300 in the embryonic chick nervous system. AB - In a previous study we described a 300 kDa, developmentally regulated protein identified in embryonic chick neural retina with a monoclonal antibody. Because this protein has been shown to be undetectable in the adult nervous system, and the monoclonal antibody is species-specific, the protein has been named embryonal avian polypeptide of 300 kDa (EAP-300). In the present study we have analyzed the histological expression of EAP-300 during chick embryogenesis. In the developing nervous system, EAP-300 expression was detected as early as Stage 5 (19 h), and was subsequently down-regulated to undetectable levels in the adult. Of particular interest was the association of EAP-300 with putative barriers of neuronal growth, such as the telencephalon/diencephalon glial knot, the dorsal midline in the mesencephalon and the midline in myelencephalon, and the spinal cord roof plate. EAP-300 was also shown to be expressed by Bergmann glia during the period of granule cell migration in the cerebellum. The expression of EAP-300 by radial astrocytes was confirmed in culture by immunofluorescent co-labeling with a MAb to EAP-300 and the R5 MAb, which is a radial astrocyte-specific marker. It has also been shown that EAP-300, when immunopurified from embryonic brain under non-dissociating conditions, co-purifies with a neural keratan sulfate proteoglycan that is also associated with CNS barrier structures during brain development. The restricted expression of EAP-300 in nervous tissue, particularly in CNS barrier structures, suggests that EAP-300 may play an important, but transient, role in the development of the chick nervous system. PMID- 1600625 TI - Effects of in utero ethanol exposure on the development of LHRH neurons in the mouse. AB - Prenatal ethanol exposure has been shown to result in craniofacial malformations as well as alterations of central nervous system morphology and function. Previous studies have demonstrated that acute ethanol exposure on gestational day 7 in the developing C57BL/6J mouse resulted in craniofacial abnormalities similar to that of children with fetal alcohol syndrome. We investigated the effect of ethanol on the migration and number of immunoreactive LHRH (irLHRH) neurons in this strain of mouse. Pregnant mice were intubated with 2 doses of a 25% solution of ethanol 4 h apart on gestational day 7 (G7). Control animals were intubated with water. Animals were sacrificed on G14 or G18 and immunocytochemistry was used to identify irLHRH neurons that were visualized by light microscopy. Fetal ethanol administration did not substantially affect the migration of the LHRH neurons from the medial nasal placode into the forebrain on G14 or G18. The total number of irLHRH neurons was not significantly different on G14 in ethanol exposed animals as compared to the number in control animals. However, the total number of irLHRH neurons on G18 was significantly less (P less than 0.03) in 4 neuroanatomical regions in fetal ethanol-exposed mice compared to those in control mice; the nasal septum, the traverse area superior to the cribriform plate and ventromedial to the olfactory bulbs, the arch area which included the olfactory tubercle, medial septal nuclei and anterior hypothalamus in G18 fetuses, and preoptic area of the brain. Coronal investigation of the number of irLHRH neurons on G18 indicates that the loss of irLHRH neurons occurred predominantly in the medial region of the rostrum and brain. PMID- 1600626 TI - Neuronal migration on laminin in vitro. AB - Chick sympathetic (E-9) or telencephalic (E-7) neurons were cultured at low density on poly-DL-ornithine (PORN), poly-L-lysine (POLS), laminin or laminin covered PORN or POLS and monitored with time-lapse videomicroscopy. Neurons migrated on laminin, or laminin-covered PORN or POLS, but not on PORN or POLS alone. Neuronal migration did not involve interactions with other cells indicating that neurons are capable of independent migration when exposed to a laminin substrate. PMID- 1600627 TI - Conditioned place preference from ventral tegmental injection of morphine in neonatal rats. AB - When given peripherally, morphine produces a conditioned place preference (CPP) in adult and infant rats. In adults, morphine injected into the ventral tegmental area (VTA) is reinforcing and likely acts by activating mesolimbic dopamine neurons. Little is known of the neurobiological basis of reinforcement in the immature animal. To test whether the neural substrate of drug reinforcement is similar in adults and infants, 4-day-old pups were injected with one of 4 doses (0.05, 0.15, 0.45, 1.35 micrograms) of morphine or the vehicle directly into the VTA and were immediately confined to an odor-cued environment for 30 min. They were then tested for a preference between the cued environment and unadulterated wood shavings. The low dose of morphine (0.05 micrograms) injected into the VTA significantly increased duration of time spent in the conditioned environment, demonstrating conditioned preference for the conditioned area over the unscented area; the most effective injection sites were directly into the VTA. Stimulation of structures just outside the VTA, and higher doses of morphine were ineffective. On the basis of these findings we conclude that the neural substrates of reward in the neonate are similar to those of the adult. PMID- 1600628 TI - Evidence that the earliest generated cells of the murine cerebral cortex form a transient population in the subplate and marginal zone. AB - We used bromodeoxyuridine to label the earliest generated cells of the murine cerebral cortex while they were dividing, and then observed their distributions at several instances later in development. Shortly before birth, many of the labelled cells were either above the cortical plate, in the marginal zone, or below it, in the region known as the subplate in other species. These cells had disappeared by postnatal day 21. PMID- 1600629 TI - Infraorbital nerve blockade from birth does not disrupt central trigeminal pattern formation in the rat. AB - We tested the hypothesis that patterned primary afferent impulse activity during early postnatal periods is necessary for central trigeminal pattern formation. Newborn rats had their whiskers trimmed daily and new slices of slow release polymer containing the sodium channel blocker, tetrodotoxin, were placed under the infraorbital nerve every 8 h for up to 9 days. Electrophysiological recordings indicated that trigeminal ganglion cells were unresponsive to peripheral stimuli and chronically silenced. Trigeminal ganglion cell numbers were unaffected by nerve blockade. Cytochrome oxidase staining patterns in the trigeminal brainstem complex, thalamus, and barrel cortex were normal on postnatal day 1, 3, 5, 7, or 9 (n = 4 each). Whisker-related patches were of normal sizes and staining densities. Similar negative results were obtained in 9 rats in which whiskers were trimmed daily and the long-acting local anesthetic bupivacaine was injected into the whisker pad at 2.5- to 4-h intervals from birth to sacrifice on postnatal day 5-9. Cytochrome oxidase staining patterns and patch properties again did not differ from normal. Thus, trigeminal pattern formation occurs even when the entire infraorbital nerve is silenced from birth. PMID- 1600630 TI - Intracellular Ca2+ and N-methyl-D-aspartate-stimulated neuritogenesis in rat cerebellar granule cell cultures. AB - Week-old rat cerebellar granule cells were grown in the presence of the cell permeable calcium chelating agent BAPTA-acetoxy methyl ester (BAPTA-AM) for the first 8 h in vitro. There was a dose-dependent inhibition of process outgrowth with an IC50 of approximately 5 microM. Neurite outgrowth could be partially recovered by the addition of N-methyl-D-aspartate (NMDA; 50 microM) to BAPTA-AM treated cells. Phorbol ester stimulation of treated cells evoked a profound inhibition of neuritogenesis compared to a stimulatory effect on control cultures. The inhibition of growth caused by phorbol esters could not be reversed by NMDA co-addition. Neurites extended by BAPTA-AM-treated granule cells were thinner than in control cultures and did not form elaborate growth cones even when growth was stimulated by NMDA. The distribution of tyrosinated and acetylated alpha-tubulin in the processes of BAPTA-AM-treated cells appeared similar to that in controls. However, rhodamine-phalloidin labelling of microfilaments in the cell cultures emphasised the loss of an elaborate actin rich growth cone in BAPTA-AM-treated cells even when neurite formation was partially recovered. These results indicate the importance of [Ca2+]i in the production of neurites from cerebellar granule cells in vitro. PMID- 1600631 TI - Acute hypoxia induces specific changes in local cerebral glucose utilization at different postnatal ages in the rat. AB - The quantitative autoradiographic 2-[14C]-deoxyglucose technique (2-DG) was applied to measure the effects of an acute hypoxic exposure on local cerebral metabolic rates for glucose (LCMRglcs) in the 10 (P10)-, 14 (P14)-, and 21 (P21) day-old rat. The animals were exposed to hypoxic (7% O2/93% N2) or control gas mixture (21% O2/79% N2) for 20 min before the initiation and for the duration of the 2-DG procedure. Lumped constants were not affected by hypoxia at any age. At P10, the exposure to the hypoxic gas mixture induced a generalized increase in LCMRglc which affected 41 structures of the 45 studied. At P14, average cerebral glucose utilization was similar in hypoxic and control rats. LCMRglc increased in 5 areas and decreased in 11 regions, mainly brainstem and respiratory areas in hypoxic rats. Finally, at P21, LCMRglc decreased in 11 structures of hypoxic rats. The increase in LCMRglc in the hypoxic 10-day-old rat likely reflects stimulation of anaerobic glycolysis. Conversely, at P14 and P21, when the brain has become more dependent upon oxygen supply for its energy metabolism, levels of LCMRglc are similar in both groups of animals or decreased in a few structures of hypoxic compared to normoxic rats. The results of the present study show that the immature brain responds to an acute hypoxic insult in a specific way according to its maturational state. They are also in good accordance with the higher resistance of the immature animal to oxygen deprivation. PMID- 1600632 TI - Development of antioxidant enzymes in rat brain and in reaggregation culture of fetal brain cells. AB - The development of antioxidant enzymes in rat brain and reaggregation cultures of fetal brain cells was studied from embryonic day 15 to postnatal day 45. Both in vivo and in culture, the copper-zinc superoxide dismutase activity first increased and then decreased with age, whereas the manganese superoxide dismutase activity increased throughout the period. Catalase showed a maximum activity at day 5 after birth, thereafter decreasing to adult level around day 30, both in vivo and in culture. The glutathione peroxidase activity increased from the first week after birth and reached adult level at day 45. In culture, the activity of this enzyme was slightly lower. The good correlation between the development of the antioxidant enzymes in vivo and in culture suggests that reaggregation cultures might be a valuable system for studying defense mechanisms against free radicals in the brain. PMID- 1600633 TI - Transient patterns of serotonergic innervation in the rat visual cortex: normal development and effects of neonatal enucleation. AB - The transient aggregation of serotonin (5-HT)-containing fibers in the early development of rat visual cortex was examined immunohistochemically. The aggregation of 5-HT immunoreactive (IR) fibers consisted of three stages which were classified according to the course of time and degree of space occupied. The primary aggregation appeared in the subplate and moved upward along the development of the cortex. The aggregation proceeded to the secondary stage in presumptive layer IV. The fibers extended in a column-like structure following the secondary aggregation and formed the tertiary aggregation. The upper edge of the tertiary aggregation formed a lattice-like pattern in layer I and its structure was recognized to be similar to the structure of a 'blob' which characterizes the primary visual cortex in monkey. This transient aggregation of 5-HT-IR fibers began in the subplate of the anterior visual cortex on postnatal day 2 (PND 2) and progressed towards the posterior. On PND 11, the secondary and tertiary aggregations were completed in the entire region. No further aggregation of 5-HT-IR fibers was observed on PND 15. The anterior-to-posterior axis in the aggregation process corresponds to the direction of differentiation in the layer structure of cortex. In order to investigate the relationship between the transient aggregation of 5-HT-IR fibers and the development of the visual pathway, the secondary and tertiary aggregation on PND 11 were observed after postnatal monocular or binocular enucleation. Enucleation of eye balls did not affect either the area occupied by the 5-HT-IR fibers in the secondary aggregation or the number of column structures in the tertiary aggregation. However, the contralateral and ipsilateral cortices of monocularly enucleated cases were irregularly shaped in the secondary aggregation. The distribution of 5 HT-IR fiber terminals in the binocular area (Oc1B) increased in density on the contralateral side in the monocular enucleation, while that of both sides in the binocular enucleation was of non-homogeneous density and were shaped irregularly. The above results suggest that the transient aggregation of 5-HT-IR fibers observed in the early stage of development of visual cortex is regulated primarily by the intrinsic factors, and that extrinsic factors, such as visual pathway input, affect the aggregation within the boundary of such intrinsic factors. That is, the visual pathway input and the input balance from both eyes affect the distribution density of 5-HT-IR fibers and the shape of the visual cortex, respectively. PMID- 1600634 TI - Transition from developing to mature patterns of acetylcholinesterase activity in rat visual cortex: implications for the time-course of geniculocortical development. AB - Patterns of acetylcholinesterase (AChE) histochemical staining in cortical area 17 differ in infant and mature rats. In infants, intense AChE activity is seen as a band corresponding to layer IV and deep layer III of the visual cortex, and this staining is associated with terminal fields of geniculocortical neurons. In adult animals, AChE activity is densest in deep layer IV and layer V and is associated with projections originating in the basal forebrain. The present study investigated the transition from developing to mature patterns of AChE staining in visual cortex. Unilateral lesions were placed in either the lateral geniculate body or the basal forebrain of rats postnatal days 8 (P8) to adulthood; the effects of these lesions on patterns of AChE activity in visual cortex were studied with histochemical techniques and optical densitometry. Lesions involving the lateral geniculate body markedly reduce AChE activity in visual cortex of P12 rats, had moderate effects in P20 rats, and had no apparent effect on AChE activity of visual cortex of rats aged P40 and older. Lesions of basal forebrain had little effect on AChE activity in visual cortex of P12 animals, increasing effect in P15-35 rats, and eliminated much of AChE staining in visual cortex of adults. The period of transition from developing to mature patterns of AChE activity in visual cortex of animals bilaterally enucleated at birth was not different from the period of transition in normally sighted animals. These data indicate that mature patterns of AChE activity in visual cortex are not achieved until well into the second month of life. If transient AChE expression is characteristic of geniculocortical neurons during the period of time in which axons are proliferating within visual cortex, then these data indicate that geniculocortical connections may be forming well into the second month of life in the rat. PMID- 1600635 TI - Hypertensive heart disease: to use or not to use diuretics? PMID- 1600636 TI - Diuretic induced long term hemodynamic changes in hypertension. A retrospective study in a MRFIT clinical center. AB - Retrospective analysis of hemodynamic factors was performed on hypertensive participants of our Multiple Risk Factor Intervention Trial (MRFIT) center to determine whether these may have a role in the higher mortality in a subgroup of special intervention (SI) participants with minor baseline electrocardiographic abnormalities. Stroke volume was estimated by a formula [SV = K(LVETxPP)x(1 + LVET/DP) where the K factor was determined using a separate group of individuals undergoing cardiac catheterization. The Pearson correlation between the two methods (dye dilution and above formula) was 0.7744 with a 95% confidence interval of 0.57-0.89 for the true correlation. In 222 SI and 186 usual care (UC) participants with no differences in stroke volume index (SVI) and cardiac output index (CI) at baseline, SVI and CI were systematically lower during the entire period of treatment in SI receiving higher average doses of thiazide diuretics. There was a moderate increase of SVI and CI in SI participants toward baseline after hydrochlorothiazide was replaced by other antihypertensive medication in the fourth year of the trial. We conclude that the lower SVI and CI could have been a contributing factor in the higher mortality in the SI group with ECG abnormalities resulting in decreased coronary flow reserve under stress conditions in these participants with probably pre-existing asymptomatic coronary artery disease. PMID- 1600637 TI - Role of gonadal hormones in hypertension in the Dahl salt-sensitive rat. AB - The present studies examine the effect of gonadal hormones on the development of hypertension in Dahl salt-sensitive rats fed a high salt diet. In the first study, administration of estradiol benzoate did not prevent hypertension in either adult ovariectomized females or intact males. In a second study, neonatal castration of males slowed the onset of salt-induced hypertension, and females that were treated neonatally with testosterone developed somewhat higher pressures that did untreated females. These data extend to Dahl S rats the findings observed originally in spontaneously hypertensive rats that blood pressure is modulated by gonadal hormones. These results are consistent with the conclusion that gonadal hormones may exert organizational effects on cardiovascular control regions of the brain during early postnatal development in rats. PMID- 1600639 TI - Hypoxic attenuation of brain stem serotonin does not influence sodium-induced hypertension. AB - Sodium (Na+)-dependent hypertension was studied in hypoxia in an effort to determine the basis for hypoxia-mediated attenuation of hypertension. Hypoxia attenuated spontaneous hypertension while Na+ increased blood pressure in SHR. A lack of interaction between the effects of hypoxia and Na+ indicated additivity of effects. As a result, hypoxia-exposed, Na(+)-supplemented SHR had similar blood pressure as did normoxic, nonsupplemented SHR although both groups had lower blood pressure than normoxic, Na(+)-supplemented SHR. Hypoxia decreased serotonin turnover (5-HIAA/5-HT) in the brain stem of SHR while supplemental Na+ had no influence on this measurement. Hypoxic exposure in DOCA-treated rats failed to prevent the development of hypertension although hypoxia decreased 5 HIAA/5-HT in the brain stem of hypoxic rats, irrespective of DOCA treatment. The finding in SHR that Na+ counteracts the protection of hypoxia could be argued to support a similar mechanism of action for hypoxia and sodium. However, the results with DOCA treatment clearly refute such an interpretation. Our findings indicate that the pressor influence of Na+ does not occur through the modulation of brain stem 5-HIAA/5-HT. PMID- 1600638 TI - Expression of rat renin in mammalian cells and its purification. AB - Rat renin cDNA was transfected into COS-7 and Chinese hamster ovary (CHO) cells and expressed under the control of the Simian Virus 40 early promoter. Conditioned media of the transfected cells showed renin activity only after trypsin treatment, suggesting prorenin was secreted into the medium. From the trypsinized serum-free culture of the transfected CHO cells active renin was purified to homogeneity by a simple three-step procedure. The active renin had similar specific activity, molecular weight, Km, pH optimum, and isoelectric point compared to native renin. The amino-terminal sequence was the same as that deduced from the renin cDNA. This suggests that the recombinant rat renin is similar to kidney renin in many respects, and is easily obtained by the present procedures. PMID- 1600640 TI - Sensitivity and reactivity to endothelin-1 in mesenteric beds and aortic rings of 4-week-old spontaneously hypertensive rats. AB - The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 4-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Mean blood pressure (124 +/- 4 vs. 97 +/- 3 mmHg) and initial perfusion pressure in the MVBs (25 +/- 2 vs. 19.7 +/- 1.2) were significantly higher in SHR. Reactivity to endothelin-1 was increased in MVBs of SHR, as indicated by the maximum perfusion pressure obtained (223 +/- 8 vs 155 +/- 7 mmHg, p less than 0.001), whereas there was no significant difference in sensitivity between the two strains (EC50 values: 50 +/ 12 and 80 +/- 15 pmol, respectively). By contrast, in aortic rings reactivity and sensitivity to endothelin-1 were similar in both strains, (EC50s: 1.8 +/- 0.12 and 1.4 +/- 0.1 nM). Reactivity to norepinephrine was increased in MVBs, but reduced in aortic rings of SHR. The unchanged sensitivity to endothelin-1 and the unspecifically increased reactivity in the MVBs of SHR to endothelin-1 and norepinephrine indicate rather a change in vascular structure and not a functional abnormality. These results suggest that hyperreactivity to endothelin 1 may not be a primary hypertensive mechanism in genetic hypertension. PMID- 1600641 TI - Relationship of stress testing blood pressure with electrocardiographic and fundoscopy indices of hypertensive end-organ damage. AB - In our study we tested firstly, whether BP changes induced by laboratory stress testing could be better related than resting blood pressure (BP) to hypertensive target-organ damage (TOD) and secondly, whether an exaggerated reactivity to stress testing might be associated with an increased prevalence of TOD. In 49 untreated essential hypertensives, BP measured at sitting rest and during a variety of stressful situations was related to the presence of TOD, assessed by electrocardiography (ECG) and fundoscopy examination. The degree of TOD was significantly correlated to resting SBP; neither SBP at peak of isometric or dynamic exercise, nor SBP during mental test showed a greater correlation with TOD than resting SBP (NS). A large variability of individual's level of BP reactivity across the different laboratory tests was observed. Patients were arbitrarily dichotomised into groups according to a hyperreactive or normoreactive response to each stress testing; patients classified as hyperreactive (SBP increase greater than upper 95% confidence limit) did not disclose a greater rate of cardiac and ocular damage than normoreactors (NS). In conclusion, stress BP does not increase the strength of relationship with TOD compared to resting BP. Cardiovascular reactivity differs according to the laboratory stimulus employed and an exaggerated BP rise during stress testing is not associated with an increased rate of TOD. PMID- 1600642 TI - Sex-dependence of body fat distribution in patients with obesity and hypertension. AB - The relationship of body fat distribution with blood pressure, fat cell weight and extracellular fluid volume was studied and compared in 20 obese hypertensive men and 20 obese hypertensive women of similar age, degree of overweight and blood pressure level. Body fat distribution, as reflected by the ratio between waist and hip circumference (W/H ratio), was significantly higher in male than in female obese patients. The W/H ratio was positively and independently correlated with systolic arterial pressure both in males and females. However, for the same W/H ratio, systolic arterial pressure was higher in females. The W/H ratio was positively correlated with gluteal fat cell weight only in males and not in females. Both in males and females, the W/H ratio was positively correlated with extracellular fluid volume, independently of the level of blood pressure level and/or the degree of obesity. The study provided evidence that the relationship between body weight and blood pressure in obese hypertensives is affected by the sex-dependence of body fat distribution with possible interferences on fat cell weight and extracellular fluid volume. Several epidemiological studies have emphasized the positive correlation observed between body weight and blood pressure in many. Many investigations have documented the association of blood pressure with body weight, weight to height, overweight or other indices of fatness such as skinfold thickness. However, the correlation coefficients of these different relationships were found constantly small, indicating that the relationship between overweight and blood pressure is somewhat complex. In patients with hypertension, body weight was shown to be strongly related with the levels of both blood pressure and extracellular fluid volume. On the other hand, patients with overweight and hypertension were found to be principally affected by hypertrophic obesity, as shown by the evaluation of fat cell weight. However these findings were exclusively observed in males. No solid data were reported in females. The relationships between body weight and extracellular fluid on one hand, and between body weight and fat cell weight on the other hand, are certainly different in males and in females. First, in females, extracellular fluid volume is submitted to cyclic changes in sodium balance involving the effect of sex steroid hormones. Second, body fat distribution, a parameter which is weakly correlated to blood pressure, is different in males and females. In males, body fat predominates in the upper part of the body while, in females, adiposity is mainly observed in the lower part of the body.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1600643 TI - Actions of L- and D-arginine and NG-monomethyl-L-arginine on the blood pressure of pithed normotensive and spontaneously hypertensive rats. AB - We have examined the depressor effects of L- and D-arginine on the diastolic blood pressure of pithed normotensive Wistar (NW), Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats after the administration of a single bolus injection of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L NMMA). A single bolus intravenous injection of L-NMMA, 30 mg/kg, produced an increase in both the systolic and diastolic blood pressure of pithed rats. Injections of bolus doses, 1-300 mg/kg, of D-arginine did not lead to sustained reductions of the blood pressure in pithed NW rats although slight decreases in the blood pressure of WKY and SH rats were observed, and these transient effects of D-arginine appeared to be more pronounced in the WKY strain. Immediately following the bolus injections of the higher doses of D-arginine a transient decrease in both the systolic and diastolic pressure occurred. In contrast to the actions of D-arginine single bolus injections of L-arginine, 1-300 mg/kg, produced a dose-dependent sustained reduction in both the systolic and diastolic blood pressures of all rats. The threshold for the depressor actions of L arginine was the same for NW, WKY and SH rats. The final dose of L-arginine (300 mg/kg), produced a significantly greater depressor effect in WKY and SH rats as compared to NW rats. The blood pressure remained elevated after the dose-response curve to D-arginine and, in order to determine whether D-arginine-treated rats are sensitive to the effects of other vasodilators and whether differences in vasoactive actions exist for vasodilators acting other than via nitric oxide synthesis, a dose-response curve to the calcium channel antagonist verapamil was constructed. Injections of verapamil, 0.1-1000 micrograms/kg, produced a dose dependent reduction in blood pressure with no difference in either threshold or sensitivity to the actions of verapamil among the three strains of rats. Our results suggest that strain differences exist between the depressor actions of L arginine and that it is possible that these differences may be due to an alteration in the endogenous levels of nitric oxide synthase and/or the activity of guanylate cyclase, however, no relationship to the hypertensive state of the spontaneously hypertensive rats was apparent. PMID- 1600644 TI - Effects of growth hormone and estrogen on rat angiotensinogen quantified by an enzyme linked immunosorbent assay. AB - An enzyme linked immunosorbent assay for rat angiotensinogen was developed based on one monoclonal antibody with high affinity for angiotensinogen and des angiotensin 1-angiotensinogen and rabbit polyclonal antibodies for angiotensinogen was developed. Serum levels of angiotensinogen were lower in female than in male rats but increased significantly after hypophysectomy. Estrogen substitution after hypophysectomy had no further stimulatory or inhibitory influence. In hypophysectomized animals continuous and intermittent growth hormone administration had clearly different effects. The results indicate that the sexually dimorphic secretion of growth hormone is involved in the regulation of circulating angiotensinogen concentrations in the rat. PMID- 1600645 TI - Closing wedge osteotomy with transpedicular fixation in ankylosing spondylitis. AB - The Smith-Petersen anterior opening wedge osteotomy of the lumbar spine is currently the accepted technique for the correction of spinal deformity in ankylosing spondylitis. It has a mortality of 10%, uses force, is uncontrolled, and fixation is often feeble. The authors have devised a posterior closing wedge with transpedicular fixation. This technique is controlled, comparatively safe, and provides secure fixation. The procedure is a relatively safe and reliable means of dealing with a dangerous operation. PMID- 1600646 TI - Aneurysmal bone cyst of the upper thoracic spine. An operative approach through a manubrial sternotomy. AB - Surgical access to T-1 and T-2 vertebral bodies through standard cervical approaches may be difficult and extensive in patients with short necks or high sterna. Adequate exposure of this area can be achieved in children, using a partial manubrial sternotomy and retraction of the manubrial halves. This procedure was successfully performed in a 14-year-old girl whose T-1 vertebra had been completely replaced by a large aneurysmal bone cyst that had produced major paraparesis. A two-stage anteroposterior excision and spinal fusion resulted in complete restoration of neurologic function, eradication of the cyst, and stabilization of the cervicothoracic spine. The limited manubrial split approach to lesions in the T-1 and T-2 vertebrae is recommended. PMID- 1600647 TI - Magnetic resonance imaging after pedicular screw fixation of the spine. AB - Magnetic resonance imaging (MRI) of the thoracolumbar spine is valuable in the diagnosis of acute and chronic spine injuries. It allows evaluation of the nerve roots, spinal cord, and the supporting bony and ligamentous structures. Magnetic resonance imaging can be used to detect sequelae of spinal cord injury and any mechanical impingement on the spinal cord or nerve roots. Pedicular screw fixation of the spine is becoming the procedure of choice for stabilization of the lumbar spine, yet it limits the postoperative use of MRI because of marked imaging artifacts arising from the ferromagnetic properties of the used stainless steel implants. The authors have compared extensive artifacts produced by the stainless steel implants with those produced by titanium implants. Titanium implants produced fewer artifacts in the spinal canal. The use of MRI compatible materials in thoracolumbar spine stabilization would permit detailed examinations by serial MR imaging. PMID- 1600648 TI - Sonographic image of the newborn hip with positive Ortolani's sign. AB - In a screening program, 4438 newborns were examined sonographically and clinically in the first 12 hours after birth for congenital hip dysplasia. Seventy-three hips in 54 newborns were dislocated, as evidenced by positive Ortolani's signs. According to Graf's classification, all 73 hips should be Type IIC or worse, with Angle alpha less than 50 degrees and Angle beta for Type IIC of 72 degrees-77 degrees, and for Types D, III, and IV, greater than 77 degrees. Sonographic examination of the 73 hips according to Graf's criteria showed that only 16 hips were decentring and eccentric, confirming the clinical diagnosis, and the results were consistent with Graf's conclusion because their alpha-angles were less than 50 degrees and beta was greater than 77 degrees. In the remaining 57 hips, there was a disparity between alpha-angles and beta-angles. Judging by Angle alpha, these hips were of Types IB and IIA because their Angle alpha averaged 60.8 degrees (range, 51 degrees-74 degrees). Judging by Angle beta, these hips were decentring Type D or eccentric Type IIIA because their beta-angle averaged 91.3 degrees (range, 78 degrees-110 degrees). Because these 57 hips were dislocated clinically (positive Ortolani's sign) it was concluded that the beta angle is a more accurate reflection of hip pathology in the newborn than the alpha-angle. It represents the cartilaginous roof of the acetabulum, which is soft and malleable, and reflects immediately any change in the position of the femoral head. Angle alpha, however, represents the hard bony roof, and any change in the position of the femoral head is not reflected immediately on it, because bony changes take longer to be seen or evidenced. PMID- 1600649 TI - Iliopsoas bursal distension caused by acetabular loosening after total hip arthroplasty. A rare complication of total hip arthroplasty. AB - In a 58-year-old woman, a cystic mass at the ileocecal region communicated with the loosened hip prosthesis 20 years after total hip arthroplasty (THA). The preoperative arthrogram of the hip and the intraoperative cystogram suggested a one-way communication from the hip to the cystic mass. The mass was diagnosed as an iliopsoas bursitis distended by the influx of the synovial fluid from the loosened THA. PMID- 1600650 TI - Effects of nonweight bearing on the hip. AB - To evaluate the effects of nonweight bearing on joints (weight-free range, five to 92 months), bilateral hips of 20 patients with amputated lower limbs or nonunion of the femur were studied clinically and roentgenographically. The nonweight-bearing side showed a roentgenographic narrowing of the joint space of 10% or more as compared with the weight-bearing side in one half of the patients, and marked narrowing of 30% or more was observed in six patients. The degree of narrowing correlated with the degree of osteopenia expressed as a femur score. The joint space narrowing was notable in those who had onset of the nonweight bearing state at ages younger than 20 years. None of the patients who showed narrowing of the joint space had pain or motor restriction of the hip. These findings suggest that a nonweight-bearing state of normally weight-bearing joints causes deranged homeostasis of articular cartilage, which leads to its thinning. PMID- 1600651 TI - Short-term treatment with nonsteroidal antiinflammatory medications to prevent heterotopic bone formation after total hip arthroplasty. A preliminary report. AB - The effect of short-term postoperative treatment with nonsteroidal antiinflammatory medication to prevent the formation of heterotopic ossification (HO) after total hip arthroplasty (THA) was studied in two groups of patients. Group A included 46 noncemented THAs in 40 men. Eight patients (13 hips) received prophylaxis with 25 mg of indomethacin three times daily for 14 days, and 32 patients (33 hips) received prophylaxis of 650 mg of aspirin twice daily for six weeks. Six to 12 months after surgery, only one hip (aspirin treated) developed HO, this being Grade I. In group B, 17 hips in 17 patients with cemented THA received prophylaxis of 25 mg of indomethacin three times daily. Of these, 12 patients were given indomethacin from one to nine days. One year after surgery, five hips had no HO and seven hips showed a Grade I or Grade II lesion. The remaining five patients in Group B received indomethacin from 19 to 26 days; one developed HO. This study demonstrated that treatment with either 650 mg of aspirin twice daily for six weeks or 25 mg of indomethacin three times daily for the first 14 postoperative days is sufficient to prevent the formation of severe HO after THA. PMID- 1600652 TI - The femoral component in low-friction arthroplasty after ten years. AB - In 623 low-friction arthroplasties ten years after implantation, 70 hips (18.04% after 16 years) showed loosening of the femoral component. Eighty-four percent appeared within ten years. Fracture of the stem occurred in 4.3% of cases after 16 years, and resorption over 5 mm of the femoral neck occurred in 9.3%. Calcar cysts appeared in 2.9% and endosteal cavitations in 18.04% after 16 years; both findings were related to acetabular wear greater than 2 mm. Gruen's Type III (calcar pivot) was the least common loosening (6.8%) during the first ten years. After this time its incidence increased to 17.1%. Loosening of the femoral component was not related to age, weight, or activity. It was, however, associated with poor surgical technique, i.e., varus position (46%), cementation defects (34%), and/or femoral neck osteotomy on the lesser trochanter (36%). PMID- 1600653 TI - Multifocal osteonecrosis after short-term high-dose corticosteroid therapy. A case report. AB - Osteonecrosis is a common sequela of long-term steroid therapy. This paper presents the only case of multifocal osteonecrosis to occur after a short-term course of methylprednisolone for treatment of septic shock. Two years after receiving a two-week course of corticosteroid treatment, the patient developed pain in his right and left shoulders and left hip. Roentgenograms and magnetic resonance imaging revealed changes consistent with osteonecrosis of both humeral heads and the femoral head. The patient failed to respond to conservative treatment and eventually was treated with bipolar hip replacement. PMID- 1600654 TI - Meniscectomy in children and adolescents. A long-term follow-up study. AB - Thirty-nine patients treated with total meniscectomy younger than 16 years of age were studied. The average follow-up period was 21 years; 71% of the patients reported pain; 68%, stiffness; 54%, swelling; and 41%, giving way. Approximately half the patients described progression of symptoms, but only 27% were asymptomatic. Only 10% noted limitations at work, but 62% had limitations in sports. Twelve percent have had further knee surgery. Forty-nine percent received unsatisfactory subjective/functional ratings. On physical examination, 25% of patients had range of motion loss of greater than 5 degrees, 22% had thigh atrophy of greater than 1 cm, and 20% developed substantial instability. Overall, 27% received unsatisfactory objective ratings. Ninety percent of patients had abnormal roentgenograms. Changes occurred predominantly in the meniscectomized compartment. Forty-four percent of patients had unsatisfactory roentgenographic ratings. Overall ratings indicated that 63% of patients' results rated unsatisfactory. More unsatisfactory results occurred in patients with a follow-up period of longer than 26 years, in those with substantial instability, and in males. Few differences existed between medial and lateral meniscectomies or with increasing durations of symptoms preoperatively. PMID- 1600655 TI - Locked patellar dislocation with vertical axis rotation. A case report. AB - Whereas traumatic lateral dislocation of the patella is a well-described clinical entity, other types of patellar dislocations, specifically those that involve patellar rotation, are unusual. These rare types also present a therapeutic problem in which reduction often requires a general anesthetic and, possibly, an open procedure. A 16-year-old boy sustained a laterally directed blow to his knee, resulting in dislocation of the patella. The patella had rotated 90 degrees in the vertical plane and became wedged against the lateral femoral condyle. Initial attempts at closed reduction in the emergency room and under general anesthesia in the operating room were unsuccessful, and the patient required open reduction. A similar type of dislocation has been described; however, the patella is usually intercondylar. The tear along the medial side was extensive enough to allow the patella to dislocate lateral to the lateral femoral condyle, making this a unique case. In these instances of rare patellar dislocation, the surgeon should be prepared to perform an open reduction, because attempts at closed reduction even with a general anesthetic may be unsuccessful. PMID- 1600656 TI - The strain distribution in the upper tibia after insertion of two different unicompartmental prostheses. AB - The strain distribution in the proximal tibia in seven human autopsy specimens was investigated with strain-gauge rosettes attached on the medial proximal aspect of the tibia. The strains measured were about the same on the proximal bone and on the bone in the metaphysis. The direction of the minimal principal strain (compression) was about 45 degrees counterclockwise (left knee). After insertion of a unicompartmental prosthesis medially, a non-constrained prosthesis with a loose meniscus-bearing and a constrained prosthesis, the tensile strain was about four times higher in the most anteromedial gauge. No significant differences were found between prostheses. Tests were also performed with the two prostheses inserted into three plastic models. The constrained prosthesis was more sensitive to outward rotation of tibia versus femur, which made the femoral component climb up the slope of the tibial component and caused a marked change in the strain distribution compared to loading in the neutral position. With the other prosthesis, a malpositioning of the tibial component medially caused the meniscus bearing to lie close to the medial rim of the tibial component. An external rotation of tibia then made the system constrained and dramatically changes the strain distribution. PMID- 1600657 TI - Long-term results for the McKeever patellar resurfacing prosthesis used as a salvage procedure for severe chondromalacia patellae. AB - From July 1972 until September 1985, 28 patients with a mean age of 36 years who had advanced arthritis of the patella were treated with a resurfacing arthroplasty using the McKeever prosthesis. The opposing articular surface of the femur appeared normal in 19 patients. The 28 patients had had a total of 50 previous operations on the patella (average, 1.8 operations per patient). These included 15 arthroscopic or open debridements, 14 lateral releases, six Maquet tibial tubercle elevations, six open patellar ligament transpositions, and seven open procedures for reduction and fixation of patellar fractures. Every case was observed postoperatively from a minimum of four years to a maximum of 16 years (mean, 8.1 years). Results were evaluated according to a patellar rating scale at five and eight years postoperatively. Seventeen of 24 were rated good or excellent at five years. Of the three poor results at five years, two were attributed to tricompartmental osteoarthrosis and were revised to total knee arthroplasties. There were no significant complications in the series. No patients had postoperative patellar instability or prosthetic loosening. Prolonged physical therapy rehabilitation (mean, 4.6 months) was necessary for patients to regain maximal ranges of motion, muscle strength, and endurance. PMID- 1600658 TI - Accuracy of clinical isometry and preload testing during anterior cruciate ligament reconstruction. AB - To determine the effect of suture elongation on the accuracy of tension isometers, an anatomic specimen was used to measure peak loads on suture materials placed in extreme nonisometric positions. Accuracy and reproducibility were determined for three tension isometers, and the influence of suture elongation was determined for one of them. In one device, reproducible readings ranged from -12.3% to + 23.6% of mean static loads recorded by hydraulic testing equipment; average error approached 39.1%. Values tended to be overestimated if readings ranged as high as 32.5% over specific excursion ranges. Selected suture materials were subjected to these loads, using hydraulic testing equipment. Stainless steel exhibited extremely low levels of elongation but only at large diameters. Ethibond had similar low levels of elongation but only at large diameters. Monofilament nylon exhibited significant elongation that could cause erroneous readings and nonisometric placement. The measurement tolerances of a selected tension isometer should be considered by the surgeon performing anterior cruciate ligament (ACL) substitution. Several readings, both loading and unloading, can be used to determine preload and isometry. Material properties of the selected suture and the accuracy of the tension isometer should be considered when interpreting readings from isometric positioners. This brings into question the ability of currently available tension isometers to deliver readings within prescribed tolerances for either isometry of preload testing. PMID- 1600659 TI - Biomechanical study on the load-bearing characteristics of the fibula and the effects of fibular resection. AB - The objective of this research was to investigate the load-bearing function of the fibula in relation to donor leg morbidity in patients who have had fibular resections. Biomechanical loading experiments were performed on ten anatomic specimens. Force transducers were mounted in place of resected tibial and fibular segments to allow load transmission to be measured. Load transmission through the fibula varied with ankle position. With the ankle at neutral position, the load distribution to the fibula averaged 7.12% of the total force transmitted through the tibia and fibula. Maximum loads occurred at full dorsiflexion and eversion. Resection of the proximal fibula results in a significant reduction of load through the distal fibular remnant. The values varied between 0.62% and 0.81% of the total force transmitted. When a cortex screw was introduced to anchor the distal fibula remnant to the tibia, the load distribution to the distal fibula remnant was partially restored with values ranging from 1.71% to 5.14% of the total force transmitted depending on the different ankle positions. These observations suggest that more consideration of the loading characteristics of the fibula should be taken into account in planning resection operations. PMID- 1600660 TI - Treatment of chronic heel pain by surgical release of the first branch of the lateral plantar nerve. AB - Sixty-nine heels (53 patients) with chronic heel pain had a surgical release of the first branch of the lateral plantar nerve. The average duration of heel-pain symptoms was 23 months (range, six months to eight years). No patient had less than six months of conservative treatment before surgery. The average duration of preoperative conservative treatment was 14 months. Forty-four patients (83%) had taken nonsteroidal antiinflammatory agents. Sixty-three heels (91%) had used heel cups and/or orthoses. Fifty-nine heels (86%) had received one or more injections of a steroid preparation. Thirty-four heels had developed pain initially during a sports activity. Postoperatively, 61 heels (89%) had excellent or good results; 57 heels (83%) had complete resolution of pain. The average follow-up period was 49 months. In general, heel pain resolves with conservative treatment. In recalcitrant cases, however, entrapment of the first branch lateral plantar nerve should be suspected. Surgical release of this nerve can be expected to provide excellent relief of pain and facilitate return to normal activity. PMID- 1600661 TI - Alterations in the in vivo torque-velocity relationship after Achilles tendon rupture. Further evidence of speed-specific impairment. AB - The torque-velocity relationship of the ankle plantar flexors was determined in 31 patients recovering from Achilles tendon rupture. Isokinetic torque measurements were made at speeds of 0 to 240 degrees.s-1 at 24 degrees.s-1 intervals. Measurements of instantaneous torque were made at joint angles corresponding to neutral and 10 degrees plantar flexion. In 17 patients treated surgically, there was little difference between the injured and the uninjured leg. In contrast, patients who were treated by casting exhibited major differences between the injured and uninjured legs. This difference became amplified when torque values at 10 degrees plantar flexion were compared. Additionally, the differences between the injured and uninjured legs were not uniform. The differences in torque were greatest at slow test speeds and least at fast test speeds. Comparisons of the injured surgical and injured nonsurgical legs demonstrated that the surgical group had significantly greater torque. This difference was also speed specific. These findings demonstrate that both groups exhibited speed-specific impairment with the loss of muscle strength being greatest at slow speeds. Also, the degree of impairment was dependent on the ankle position at which torque was measured. Surgical treatment provides better functional results as observed by the torque-velocity relationship. PMID- 1600662 TI - The use of the Lottes nail in the treatment of closed and open tibial shaft fractures. AB - During the years 1979 through 1987, 98 patients with 101 acute tibial fractures were initially treated with Lottes' nails at the authors' institution. Ninety-one percent of the fractures healed uneventfully. The average healing times were 15.7 weeks for the 40 closed fractures and 20.5 weeks for the 61 open fractures. Infection occurred in one of the 40 closed fractures (2.5%) and in eight of the 61 open fractures (13.1%). By Gustilo grade, infection occurred in none of the 22 Grade I fractures (0%); one of the 22 Grade II fractures (4.5%); and seven of the 17 Grade III open fractures (41.2%). Seven of the eight malunions resulted from preventable technical errors. Five of the six nonunions healed after a secondary procedure. Lottes nailing is recommended in closed fractures and Grade I and II open fractures when internal fixation is required. Grade III open fractures, treated with the Lottes nail, had a high rate of infection. PMID- 1600664 TI - The use of computed tomographic scan to assess femoral malrotation after intramedullary nailing. A case report. AB - Malrotation complicating intramedullary nailing of the femur must be recognized before healing occurs in the early postoperative period to obtain correction with the least possible effort. A 20-year-old man with more than 40 degrees of excessive external rotation required careful evaluation and demonstrated the value of computed axial tomography (CT scan) followed by derotation. PMID- 1600663 TI - Hawkins type III fracture-dislocation of the talus and diastasis of the tibiofibular joint without concomitant fracture of the malleolei. A case report. AB - A 23-year-old man injured his foot in a motorcycle accident. Roentgenograms and computed tomography scans demonstrated a Hawkins Type III fracture-dislocation of the talus with a suspected disruption of the anterior tibiofibular ligament. Prompt anatomic reduction of the talus with rigid internal fixation was performed. Intraoperative stress roentgenograms confirmed the presence of a syndesmotic disruption. No cases of this injury have been reported in the literature. When no obvious fracture of the ankle mortise is present in a Hawkins Type III or IV talar fracture-dislocation, care must be taken to fully evaluate the osseous and ligamentous structures of the ankle to rule out an occult injury. Computed tomography scans, stress roentgenograms, intraoperative clinical examination, and direct visual inspection can all be used to aid in this evaluation. PMID- 1600665 TI - Giant cell tumor of the capitate. A case report. AB - Giant cell tumors in the small bones of the hand are unusual, particularly in the carpus. A 28-year-old woman developed a giant cell tumor in the capitate. After biopsy, she was treated with complete excision of the capitate with no reconstruction. Five years later she had excellent hand function and no tumor recurrence. A careful roentgenographic and pathologic examination will distinguish between aneurysmal bone cysts and giant cell reparative granulomas. Complete excision of the involved bone is recommended. PMID- 1600666 TI - Intracortical small cell osteosarcoma. AB - A case of intracortical osteosarcoma, a rare form of osteosarcoma that may radiologically simulate a variety of benign and malignant bone lesions, is described. To date, all cases have arisen in the diaphysis of either the tibia or femur, and histologically have been of osteoblastic type. In contrast, the current tumor was a small cell osteosarcoma, another uncommon variety of osteosarcoma. A summary of the reported cases of intracortical osteosarcoma is given, and the literature on small cell osteosarcoma is briefly reviewed. PMID- 1600668 TI - The effect of wire configuration on the stability of the Ilizarov external fixator. AB - The stability of the basic unit for fixation of the Ilizarov external fixation system was tested in several loading modes. The effects of varying the number of wires and the orientation of wire placement were studied. The fixation units were mounted on a plastic, simulated, long bone and tested by loading in several directions. The Ilizarov fixation ring was found to be relatively stiff in axial compression and torsion. Its stiffness in this mode was directly proportional to the number of wires in the system and independent of the configuration of wire placement. Loading in bending and in shear provided much lower levels of stiffness, and this was dependent on the angles formed between the wires. The addition of a wire at a minimum distance of 4 cm from the primary ring significantly improved bending stiffness. The use of opposed olive wires also improved shear stiffness. PMID- 1600667 TI - Bone mastocytosis. A report of nine cases with a bone histomorphometric study. AB - Bone mastocytosis is characterized radiographically in some patients by diffuse osteosclerosis and in others by demineralization. The reason for these apparently conflicting bone features is unknown. Bone remodeling and marrow mastocytosis infiltration were studied in nine cases of mastocytosis with bone marrow involvement. Six men, ranging from 42 to 78 years of age, and three women, 43, 55, and 73 years old, comprised the series. Two patients had severe and diffuse osteosclerosis. Seven had diffuse demineralization, with crushed vertebrae in four, suggesting common osteoporosis. In three of the seven, cutaneous mastocytosis was absent. Bone biopsies were undecalcified and stained with toluidine blue. In the seven patients with demineralization, the number of marrow mastocytes was increased (154 +/- 24 versus 2 +/- 0.5/mm2 in normal postmenopausal osteoporosis). Mastocyte nodules covering 1-9% of the marrow area were present in all seven patients. These patients showed a significant increase in remodeling; bone formation rate was increased, coupled with a decrease in mean wall thickness. Concomitantly, osteoclast surfaces were increased, with an increased amount of bone resorbed. The two patients with diffuse osteosclerosis had a markedly different histology; mast cell infiltration was dramatically increased (mastocyte count greater than 1000/mm2) with diffuse marrow fibrosis. Bone volume was increased as well, and most of the bone was woven with an intratrabecular mineralization defect. High bone remodeling and decreased osteoblast activity can explain bone loss in mastocytosis with demineralization. Mastocytosis with osteosclerosis is characterized by a more extensive marrow mast cell infiltration and fibrosis. PMID- 1600669 TI - Anatomical and clinical studies on lumbar disc degeneration. 1950. PMID- 1600670 TI - Effects of repetitive strains on vertebral end plates in young rats. AB - A histologic study of vertebral end plates was performed on young rats' tails subjected to intensive passive motion. Seven six-week-old rats had two-hour motion cycles daily, for two months. Histologic changes of proximal caudal vertebrae in the experimental group were compared with those of a control group of seven rats of the same litter which were allowed to grow freely without mechanical stress. The main findings were three striking protrusions of disk tissue into end plates, not observed in the control animals. End plate axial bulges lacking spindle-shaped cells and an increase in chondrocytes in the adjacent articular cartilage were observed. The growth-plate thickness was uneven and was absent in some areas, with disorganization of chondrocyte columns. All of these findings were present to a lesser degree in the control group and appeared to be similar to histologic changes observed in Scheuermann's disease. PMID- 1600671 TI - Parkinson's disease and femoral neck fractures treated by hemiarthroplasty. PMID- 1600672 TI - Single- versus double-level nerve root compression. An experimental study on the porcine cauda equina with analyses of nerve impulse conduction properties. AB - Double-level nerve root compression had a greater effect on nerve impulse conduction, recorded as tail muscle action potential amplitude, than single-level compression at both 10 and 50 mm Hg. If the distance between the two compression sites at 10 mm Hg compression was increased from one vertebral segment (10 mm) to two vertebral segments (30 mm), the reduction of muscle action potential amplitude was further enhanced. These observations may give new insight into the pathophysiology of cauda equina compression in spinal disorders such as stenosis. PMID- 1600673 TI - Diagnosing instability. AB - The various definitions of instability are reviewed and preference is given to the definition of instability as a loss of stiffness. This definition fits with current laboratory observations. Roentgenographic changes, particularly those associated with degeneration, have no relationship to instability. Multiple roentgenographic images can be of use, but accuracy is limited, and often valuable information at midmotion range or in other planes is missing. Stereoroentgenography appears to offer some promise, but implanted metallic markers are necessary to attain adequate accuracy. Ionizing radiation dose levels are of concern in these techniques. External fixation techniques appear to be of use in some patients. Kinematic linkages and frames containing infrared light emitting diodes are extremely promising, because they give kinematic information in detail. PMID- 1600674 TI - Current assessment of spinal degenerative disease with magnetic resonance imaging. AB - Radiography (plain roentgenography, myelography, computed tomography (CT), computed tomographic myelography) has been used to identify morphologic changes involving the various components of the diskovertebral unit. Added to this armamentarium of imaging techniques is magnetic resonance (MR) imaging, with its superior ability to define anatomy, its improved contrast sensitivity, and its potential to provide unique biochemical and physiologic information. The authors review the current use of MR imaging in defining degenerative changes in the spine including the various patterns of herniation, annular tears, canal stenosis, and the use of gadolinium-diethylenetriamine-pentaacetic acid for previously unoperated and operated patients. Prospective studies have compared surface-coil MR imaging, CT, and myelography in the evaluation of disk herniation and stenosis and found an 82.6% accuracy between MR imaging and surgical findings for the type and location of the disease. Recent experience with precontrast and postcontrast MR imaging in the postoperative lumbar spine indicated that it was 96% accurate in differentiating scar from disk in 44 patients at 50 reoperated levels. Three-dimensional imaging is, more and more, becoming an integral part of routine MR imaging. The theoretical and practical advantages of three-dimensional imaging are several and include a theoretical increase in the signal-to-noise ratio over two-dimensional imaging (by the square root of the number of partitions selected), the ability to obtain thin contiguous slices from the volume without the problem of cross-talk found in two-dimensional imaging, more accurate slice thickness than that achieved in two-dimensional imaging, and a reduction in susceptibility artifacts. Different three-dimensional techniques are capable of providing either high or low signal intensity cerebrospinal fluid (CSF), with excellent suppression of CSF pulsation artifacts. Certain sequences provide a high enough signal intensity that a computer algorithm may be used to display the CSF in a rotating three-dimensional manner, similar to a myelogram. This three-dimensional myelographic image has the potential of providing the clinician with a global assessment of the CSF spaces, an advantage previously lacking with other imaging techniques. PMID- 1600675 TI - Indications for lumbar spine fusion in the adult. AB - More than 20,000 lumbar spine fusions are performed annually in the United States. Results of surgery unfortunately are inconsistent and may reflect unsatisfactory patient selection. Indications for lumbar arthrodesis may arise in degenerative disk disease, deformity, distal extension of previous arthrodesis, trauma, spondylolisthesis, and spinal stenosis (in association with diskectomy or decompression). There are several techniques in the assessment of potential candidates for low lumbar arthrodesis. PMID- 1600676 TI - Bloodborne pathogens: the $821 million standard. PMID- 1600677 TI - EMS physician advisors: duties and responsibilities. PMID- 1600678 TI - Prescription drug abuse: it could happen to somebody's mother. PMID- 1600679 TI - Sunscreen Q & A. PMID- 1600680 TI - Medicare Fee Schedule: the good, the bad and the ugly. AB - We must learn to work with the system. Unfortunately, today's coding is such that you cannot leave this to your coding clerk, as many of us have done in the past. The specificity of the new system will demand that the physician be actively involved in coding of all E/M services. One must consider using all levels of codes. The person who learns to correctly work with the system and charge correctly for services rendered will be better paid and run less risk of denials and penalties. So much to say and so little space to say it. PMID- 1600681 TI - Breast cancer screening. Results and follow-up for Colorado women. PMID- 1600682 TI - Cognitive enhancers illegal, says FDA. PMID- 1600683 TI - New labeling and patient insert for triazolam approved by FDA. PMID- 1600684 TI - ASHP therapeutic guidelines on antimicrobial prophylaxis in surgery. ASHP Commission on Therapeutics. PMID- 1600685 TI - Mesalamine and olsalazine: 5-aminosalicylic acid agents for the treatment of inflammatory bowel disease. AB - The history, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, and dosage and administration of rectal mesalamine and oral olsalazine in the treatment of inflammatory bowel disease (IBD) are reviewed. The high incidence of toxicity associated with sulfasalazine led to the development of the nonsulfonamide 5-aminosalicylic acid products mesalamine and olsalazine. The exact mechanism of action of these agents in the treatment of IBD is unknown. In clinical trials, mesalamine was shown to be as effective as or more effective than sulfasalazine or corticosteroids in treating active ulcerative colitis, proctitis, and proctosigmoiditis. Mesalamine is effective in the maintenance of remission in patients with ulcerative colitis. Several studies have demonstrated the effectiveness of olsalazine in the treatment of active mild to moderate ulcerative colitis. Olsalazine is also effective in the maintenance of remission of ulcerative colitis. The most common adverse effect associated with mesalamine enemas is perianal irritation or trauma secondary to insertion. The most common adverse effects associated with olsalazine are dose-dependent watery diarrhea and gastrointestinal upset. The recommended dosage of the mesalamine enema for the treatment of active mild to moderate ulcerative colitis is one 4-g (60-mL) retention enema daily for three to six weeks. The dosage of mesalamine suppositories for the treatment of active ulcerative proctitis is one 500-mg suppository inserted rectally twice daily for three to six weeks. The dosage of olsalazine is 1 g daily in divided doses for the maintenance of remission of ulcerative colitis. Both rectal mesalamine and oral olsalazine provide clinicians with an effective therapeutic option for the treatment of ulcerative colitis, proctosigmoiditis, and proctitis in patients unresponsive to or intolerant of the effects of sulfasalazine or corticosteroids. PMID- 1600687 TI - Complications of home parenteral nutrition. AB - The complications associated with home parenteral nutrition (HPN) and their relationship to length of therapy were studied. The medical records of 56 patients treated with HPN (age range, 6 months to 82 years) were retrospectively reviewed to study complications associated with HPN. Of the 56 study patients, 30 (53.6%) had complications related to HPN, 18 (32.1%) had complications not related to HPN, and 8 (14.3%) had no complications. Of the 365 total complications noted, 125 (34.2%) were related to HPN. The mean +/- S.D. interval between initiation of HPN and occurrence of a complication was 1.25 +/- 1.73 years (mean +/- S.D.). Patients were more likely to have fluid or electrolyte complications or glucose intolerance in the first year of therapy and catheter related complications later in the course of treatment. The first episode of septicemia occurred 2.1 +/- 1.8 years (mean +/- S.D.) after the initiation of HPN. The risk of developing catheter-related septicemia was higher for patients on long-term HPN therapy and for young patients. Patients receiving HPN should be carefully monitored for complications such as fluid and electrolyte abnormalities and glucose intolerance, which commonly occur early in the course of therapy; later complications of HPN include catheter-related infection, thrombosis, and breakage or dislodgement. PMID- 1600686 TI - Bioequivalence of verapamil hydrochloride extended-release pellet-filled capsules when opened and sprinkled on food and when swallowed intact. AB - A study was performed to determine whether verapamil hydrochloride administered in extended-release pellet-filled capsules is bioequivalent to the same formulation administered by sprinkling the contents of the capsules onto food. Thirty-two healthy subjects participated in the randomized, two-way crossover study. In treatment A, the subjects swallowed the contents of a verapamil hydrochloride extended-release pellet-filled capsule, 240 mg, that had been sprinkled on applesauce. In treatment B, the subjects swallowed the same type of capsule intact. Blood samples were drawn at baseline, every hour for 10 hours, and at 12, 15, 24, 30, 36, and 48 hours after each dose administration. The plasma was analyzed for verapamil and norverapamil by high-performance liquid chromatography. The following calculations were performed: AUC0-48, AUC0 infinity, Cmax, tmax, and k. Results for the two treatments were compared by analysis of variance. There were no significant differences between the AUC0-48, AUC0-infinity, Cmax, tmax, and k for the two methods of dose administration. For verapamil the differences for all variables were less than 5%, and for norverapamil the differences were less than 4% for all variables except tmax (9.5%). The 90% confidence intervals were within acceptable limits for all variables except the norverapamil tmax comparison. Sprinkling the contents of extended-release pellet-filled capsules onto food provides verapamil hydrochloride that is bioequivalent to that obtained from the intact capsules. PMID- 1600688 TI - New calcium-channel blockers: improved therapy? PMID- 1600689 TI - Criteria for use of agents for extrapyramidal adverse effects in adult, adolescent, and child inpatients and outpatients. PMID- 1600690 TI - Selection of patients with the antiphospholipid syndrome by serological measurement of lupus anticoagulant activity in conjunction with anticardiolipin antibodies. AB - The significance of anti-cardiolipin antibodies (ACLA) in patients with a range of autoimmune and infective disorders was investigated in this study. Although lower levels of IgG and IgM ACLA were present in 77 of 400 patients' sera (19%), high antibody levels were found in less than 5% of patients. These latter patients belonged to three clinical categories: patients with connective tissue disease (CTD), infectious mononucleosis or biological false positive serology. An assay was developed to measure lupus anticoagulant (LA) activity in serum: significant LA activity was found in the CTD patients alone (in 6 of 15 tested) and all of these had high titre ACLA. Features of the antiphospholipid syndrome (APS) were present in these six patients but also in three additional CTD patients with normal LA results and high levels of ACLA. In two CTD patients with APS features, the high ACLA were of IgM isotype. These results stress the importance of measuring both ACLA and LA in an investigation of the APS: a high positive ACLA supports the diagnosis of APS, particularly in patients with autoimmune disease, whilst a high positive ACLA in association with LA activity is specific for this syndrome. PMID- 1600691 TI - Successful therapy with ribavirin of late onset respiratory syncytial virus pneumonitis complicating allogeneic bone transplantation. AB - A 21-year-old patient developed interstitial pneumonitis nine months post bone marrow transplant for acute myeloblastic leukaemia. Immunofluorescence of broncheoalveolar lavage fluid revealed the presence of respiratory syncytial virus (RSV). Aerosolized ribavarin therapy resulted in rapid resolution of the pneumonitis with full recovery without any side effects. Ribavarin therapy should be considered early in the management of BMT patients who develop RSV pneumonitis. PMID- 1600692 TI - The significance of neopterin and biopterin concentrations at presentation in haematological malignancies. AB - Urinary neopterin and biopterin concentrations were measured in 32 healthy controls and 53 patients with newly diagnosed haematological malignancies classified and staged by accepted criteria. The neopterin concentrations were only significantly raised in chronic lymphocytic leukaemia at stages III-IV. Total biopterin concentrations after oxidation with iodine at acid pH were decreased in chronic lymphocytic leukaemia stages O-II, multiple myeloma, and acute myeloid leukaemia but not in chronic lymphocytic leukaemia stages III-IV. Although of research interest, neopterin concentrations proved of little prognostic value at presentation, but taken with the biopterin concentration they may be useful for the assessment of tumour activity. PMID- 1600693 TI - The accuracy and clinical interpretation of serum ferritin assays. AB - The accuracy of methods used to assay serum ferritin was determined in two ways. In one a serum, to which the UK ferritin standard had been added, was issued to the participants in an inter-regional quality assurance scheme. The overall recovery was close to that expected. For the second assessment a series of sera from individuals of known iron status were issued. Differences between assay results related to the method of assay though the immunoradiometric and ELISA methods gave results which were close to each other. The variation in clinical interpretation applied to assay results when ferritin concentrations around the upper and lower limits of normal were assayed was more than could be accounted for by method imprecision and indicates that inappropriate reference ranges are in common use. 'Indeterminate', a proper clinical interpretation when the imprecision of a technique should prevent a definite response, was inadequately used. PMID- 1600694 TI - An evaluation of leucocyte analysis on the Coulter STKS. AB - The performance of leucocyte analysis on the Coulter STKS (Coulter, Hialeah, FL, USA) was evaluated for accuracy, precision and reliability. The results were compared with those obtained from visual examination of a Romanowsky stained blood film together with the automated WBC-diff. from the Technicon H*1 (Technicon, Tarrytown, NY, USA). The relationship between the number of cells counted per WBC-diff. and the WBC count of the sample was established. Precision of the STKS WBC-diff. was acceptable on blood samples with normal and low WBC counts. Correlation with an 800 cell manual WBC-diff. (n = 104) was excellent (r = 0.97, 0.97, 0.83, 0.98 and 0.53 for neutrophils, lymphocytes, monocytes, eosinophils and basophils respectively). Blood specimens, collected into dipotassium EDTA, could be stored at 20-25 degrees C for at least 8 h with no significant effect on the STKS WBC-diff. In a study of 513 patient samples, the BLASTS suspect flag gave 5.4% false positives and zero false negatives, the VARIANT LYMPHS flag gave 1.5% false positives and 0.4% false negatives, and the IMM GRANS/BANDS flag gave 30.8% false positives and 2.3% false negatives. Several instrument and sample related problems were encountered during this study. Despite these limitations, the STKS can provide efficient 5 part WBC-diffs. and effective screening for WBC abnormalities. PMID- 1600695 TI - A method for the preparation of methaemoglobin-containing human red cell suspensions. AB - The variables affecting the formation and stability of intracellular methaemoglobin were examined. A method is proposed for the preparation of intracellular methaemoglobin specimens. PMID- 1600697 TI - Acute myelomonocytic leukaemia and 48,XXY, +8 chromosome anomalies. PMID- 1600696 TI - Fatal bleeding in a patient with a non-specific PT and APTT inhibitor. PMID- 1600698 TI - A computerized database for haemophilia patient records. AB - A microcomputer database system for the storage, retrieval, and statistical analysis of data associated with the treatment of haemophilia and other defects of haemostasis is described. The hardware requirements are an IBM compatible PC with both hard and floppy disc drives and a suitable printer. The system was written using Smartware II, a powerful integrated software package which incorporates database, word processor, spreadsheet and communications functions. The programs were written with flexibility in mind and can be readily adapted to accommodate the work patterns of any haemophilia centre. This system has now been operational in the Regional Haemophilia Centre at the Manchester Royal Infirmary since January 1990. Its introduction has led to a marked improvement in the efficiency of patient data handling with significant savings in staff time. PMID- 1600699 TI - The red cell distribution width in sickle cell disease--is it of clinical value? PMID- 1600700 TI - Why we need to shout about diabetes research! PMID- 1600701 TI - Aetiology of diabetic foot ulceration: a role for the microcirculation? AB - Neuropathy, mechanical stress, and macrovascular disease are involved in the pathogenesis of diabetic foot ulceration. Implicit in the development of gangrene and ulceration is the recognition that these factors interact with the microcirculation, resulting in the failure of skin capillary flow to meet nutritive requirements. There is little evidence to associate structural microangiopathy with foot microcirculatory failure. Significant functional abnormalities of the microcirculation have been defined. In accord with the haemodynamic hypothesis early hyperaemia and capillary hypertension promote more sinister late functional abnormalities with increasing duration of diabetes. These late functional abnormalities include loss of autoregulation and reduced hyperaemic responses which interact with loss of neurogenic flow regulation, disturbed endothelial function, and abnormal rheology to produce the familiar clinical picture of the diabetic foot. Ischaemia secondary to multi-segment arterial disease induces additional abnormalities of microcirculatory function which are superimposed on the pre-existing diabetic microvascular structural and functional microangiopathy. PMID- 1600702 TI - Susceptibility to diabetes and the major histocompatibility complex: the 57th residue affair. PMID- 1600703 TI - Intranasal administration of insulin with phospholipid as absorption enhancer: pharmacokinetics in normal subjects. AB - The pharmacokinetics of intranasal insulin containing a medium-chain phospholipid (didecanoyl-L-alpha-phosphatidylcholine) as absorption enhancer, was studied in normal volunteers by measuring plasma glucose, insulin, C-peptide, and glucagon. Eleven fasting subjects received 4 U insulin intravenously, 6 U subcutaneously, or three doses intranasally (approximately 0.3 U kg-1, 0.6 U kg-1, 0.8 U kg-1) in random order on five separate days. Intranasal insulin was absorbed in a dose dependent manner with a mean plasma insulin peak 23 +/- 7 (+/- SE) min after administration. Mean plasma glucose nadir was seen after 44 +/- 6 min, 20 min later than following intravenous injection. Furthermore, intranasal administration of insulin resulted in a faster time-course of absorption than subcutaneous injection, with significantly reduced intersubject variation (p less than 0.001). Bioavailability for the nasal formulation was 8.3% relative to an intravenous bolus injection when plasma insulin was corrected for endogenous insulin production estimated by C-peptide. A dose-dependent suppression of C peptide and stimulation of glucagon secretion occurred after intranasal administration of insulin. Nasal irritation from spraying was absent or slight. PMID- 1600705 TI - Body fat and overweight among children and adolescents with diabetes mellitus. AB - Body composition was assessed in 68 children and adolescents with diabetes mellitus. Body fat was measured by skinfold thickness and the results were compared with those obtained by bioelectrical impedance methods (r = 0.76, p less than 0.001). Percentage body fat from skinfold thickness estimations was 12-38%. Girls appeared to be most at risk of obesity during puberty with mean body fat 31%, significantly greater than in prepubertal girls (22%, p = 0.001) and pubertal boys (21%, p less than 0.001). Body fat increased progressively through puberty in girls, with those in late puberty (stages 4 and 5) having significantly more percentage body fat than those in earlier puberty (stages 2 and 3, p less than 0.001). Those in late puberty also received significantly more insulin per kilogram body weight (p = 0.05) and had higher HbA1 levels (p less than 0.05) than prepubertal girls. PMID- 1600704 TI - The effects of dexfenfluramine on blood glucose control in patients with type 2 diabetes. AB - Dexfenfluramine has been shown to promote weight loss in overweight people. The present double-blind study was designed to test whether the addition of dexfenfluramine to conventional oral hypoglycaemic treatment would promote weight loss and improve blood glucose control in overweight patients with Type 2 diabetes. The 34 patients studied were randomly assigned to dexfenfluramine or placebo therapy which was added for 12 weeks to their existing treatment regimens of metformin with or without a sulphonylurea. Dexfenfluramine treatment was associated with a significant reduction in weight (98.7 +/- 5.0 (+/- SE) vs 94.9 +/- 5.2 kg; p less than 0.001), BMI (35.0 +/- 1.2 vs 33.6 +/- 1.9 kg m-2; p less than 0.001), HbA1c (7.5 +/- 0.3 vs 6.3 +/- 0.2%; p less than 0.001), fructosamine (313.9 +/- 17.6 vs 274.3 +/- 10.4 mumol l-1; p less than 0.01), systolic (137 +/- 5 vs 128 +/- 6 mmHg; p less than 0.05), and diastolic blood pressure (85 +/- 2 vs 73 +/- 3 mmHg; p less than 0.001). At the end of the study period, the dexfenfluramine treated group had a significantly lower HbA1c (6.3 +/- 0.2 vs 7.2 +/- 0.4; p less than 0.05), fructosamine level (274.3 +/- 10.4 vs 313.3 +/- 16.1 mumol l-1; p less than 0.05) and diastolic blood pressure (73 +/- 3 vs 81 +/- 3 mmHg; p less than 0.03) when compared with the placebo group. In those patients treated with dexfenfluramine, the reduction in HbA1c and blood pressure did not correlate with the decrease in BMI (r = 0.44 and 0.12, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600706 TI - The prevalence of diabetic distal sensory neuropathy in an English community. AB - The prevalence of lower limb neuropathy was determined in a known diabetic population. From a general population of 97,034 subjects, a total of 1150 diabetic patients were identified of whom 1077 (93.7%) were reviewed. Neuropathy was defined as symptoms plus one abnormal physical finding, or two abnormal physical findings. An age- and sex-matched non-diabetic control group of 480 individuals was also examined by the same single observer. The prevalence of neuropathy was 16.3 (95% CI 14.6-19.0)% in diabetic patients and 2.9 (95% CI 1.4 4.4)% in non-diabetic subjects, yielding a prevalence odds of 6.75 (95% CI 3.87 11.79), p less than 0.001. In Type 1 diabetes, the prevalence was 12.7 (95% CI 8.0-17.6)% and in Type 2 diabetes 17.2 (95% CI 15.9-18.5)%. After adjusting for age, the difference was not significant (odds ratio (OR) 1.60 (95% CI 0.95 2.76)). The prevalence of neuropathy increased with age in diabetic and non diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600707 TI - The distribution and severity of diabetic foot disease: a community study with comparison to a non-diabetic group. AB - A surveillance programme was undertaken to identify all diabetic patients with foot disease in a defined population with the same age and sex structure as that of the UK. Of 1150 diabetic patients identified, 1077 were reviewed either at home or in hospital. The presence of foot deformity, amputation, and foot ulceration was determined. The site, depth, and duration of ulcers were recorded and any previous ulceration noted. All feet with ulcers were X-rayed. A non diabetic comparison group of 480 age- and sex-matched individuals were also examined by the same observer. The prevalence of past or present foot ulceration was 7.4 (95% CI 5.8-9.0)% in diabetic patients and 2.5 (95% CI 1.1-3.9)% in the non-diabetic group, yielding an odds ratio of 2.94 (95% CI 1.58-5.48) (p less than 0.001) for the occurrence of foot ulceration in diabetic patients. Of the ulcers found on examination, 39.4% were neuropathic, 24.2% were vascular, and 36.4% were mixed. Multiple logistic regression analysis of selected variables revealed that duration of diabetes, absent light touch, impaired pain perception, absent dorsalis pedis pulse, and the presence of any retinopathy were significant predictors of the presence of foot ulcers. The prevalence of amputation in diabetic patients was 1.3 (95% CI 0.6-2.0)%, but there were no amputations in the non-diabetic group. PMID- 1600708 TI - Discrimination between painful and painless diabetic neuropathy based on testing of large somatic nerve and sympathetic nerve function. AB - The syndromes of painful diabetic neuropathy and painless foot ulceration are distinct clinical entities. To investigate whether there is a pattern of nerve fibre involvement that could clearly discriminate between them, we have studied three groups of diabetic patients, 19 with painful neuropathy, 14 with painless foot ulceration, and 19 with no clinical neuropathy. Large somatic nerve fibre function was assessed by nerve conduction studies and vibration thresholds, small somatic nerve function by cooling and warming thresholds, the parasympathetic system by heart-rate dependent cardiac autonomic reflexes, and the sympathetic system by postural drop in blood pressure and plasma noradrenaline (supine and erect). Normal ranges were obtained from 25 age-matched healthy subjects. Painful neuropathy was characterized by uniform dysfunction of small somatic fibres and preserved sympathetic nerve activity (plasma noradrenaline) with a wide range of large somatic fibre and autonomic reflex abnormalities. By contrast, in painless foot ulceration there was universal severe dysfunction of all nerve fibre populations. Discriminant analysis identified peroneal motor conduction velocity as the best single variable for distinguishing between painful and painless neuropathy (81% of cases). A combination of peroneal motor conduction velocity with vibration threshold and plasma noradrenaline discriminated completely between the two clinical syndromes. These findings suggest that the key differences between painful and painless diabetic neuropathy are in large somatic and sympathetic fibre function. PMID- 1600709 TI - Serum and urinary concentrations of type IV collagen and laminin as a marker of microangiopathy in diabetes. AB - Serum and urinary concentrations of type IV collagen and laminin were measured by enzyme-linked immunosorbent assay (ELISA) in diabetic patients and compared with normal control subjects. In diabetic patients with proteinuria or with renal insufficiency, serum and urinary concentrations of type IV collagen were higher than those of control subjects (p less than 0.005). Furthermore urinary concentrations of type IV collagen and laminin were significantly higher in diabetes, even in the absence of nephropathy, than in normal controls (p less than 0.05). Urinary concentrations of type IV collagen in patients with diabetes and microalbuminuria (0.73 +/- 0.11 mg mmol-1) were significantly higher than in diabetic patients without nephropathy (0.40 +/- 0.060 mg mmol-1) (p less than 0.025). Urinary concentrations of type IV collagen may have a role as an indicator of early diabetic nephropathy. Serum concentrations of type IV collagen in diabetic patients with retinopathy were significantly higher than in normal controls (p less than 0.025). However, urinary concentrations of type IV collagen (p less than 0.05) and serum concentrations of laminin (p less than 0.025) were significantly higher in diabetic patients than normal controls and the difference between patients with and without retinopathy was not significant. PMID- 1600710 TI - Sex hormone binding globulin levels in adolescent subjects with diabetes mellitus. AB - In normal adolescents there is a pubertal fall in circulating levels of sex hormone binding globulin (SHBG) in both sexes which is not explained by classically accepted mechanisms of control of SHBG. Recent in vitro and in vivo evidence has suggested that SHBG is inversely regulated by insulin. In view of this we have compared SHBG levels in 80 adolescent subjects with Type 1 diabetes to those in 61 normal adolescents. In both normals and in Type 1 diabetic subjects there was a pubertal fall in SHBG levels. Contrary to expectations, SHBG levels were not elevated in those with diabetes, but prepubertally were significantly lower in both sexes (boys mean +/- SD, 70 +/- 28 nmol l-1, normals 130 +/- 52 nmol l-1, p less than 0.001; girls, 61 +/- 17 nmol l-1, normals 110 +/ 23 nmol l-1, p = 0.01). In pubertal subjects no differences in SHBG levels were seen between the two groups, or between either sex within any group. In subjects with Type 1 diabetes SHBG levels were unrelated to metabolic control as reflected by HbA1 but were inversely related to pubertal stage (r = 0.55, p less than 0.001). In prepubertal subjects with diabetes, in whom abnormal SHBG levels were found, these levels were weakly related to insulin dose (r = 0.33, p less than 0.05); no such relationship was found in the other groups. The significance of the abnormal SHBG levels in prepubertal children with diabetes and its relationship to any irregularities of their sexual development is unclear. PMID- 1600711 TI - Quality of life in young adults with type 1 diabetes in relation to demographic and disease variables. AB - Sixty-nine young adults (mean age 21 (range 15-25) years) with Type 1 diabetes completed measures of diabetes knowledge and quality of life. Factor analysis of the quality of life scale resulted in the identification of three subscales (social relationships, diabetes concerns, and impact). There was no relation between any of the quality of life subscales with knowledge, or with multiple versus twice-daily insulin injection regimens. Higher self-rated diabetes satisfaction was related to lower fructosamine levels and better clinic attendance (p less than 0.05). Females reported a more negative impact of diabetes on their lives compared with males (p less than 0.05). PMID- 1600712 TI - Hospital in-patient statistics underestimate the morbidity associated with diabetes mellitus. AB - Hospital in-patient statistics are an important outcome measurement in the assessment of the morbidity associated with diabetes mellitus. A prospective study of 157 consecutive admissions over a 28-day period compared diagnoses obtained from the clinical records with the ICD9 coding of the same admissions recorded at the Information and Statistics Division of the Scottish Health Service. Sixty-one percent of all discharge summaries omitted the diagnosis of diabetes. Even when admission was principally related to diabetes complications, 47% of medical and 88% of surgical discharge summaries omitted diabetes as a diagnostic category. ICD9 coding underestimated the percentage of admissions accounted for by diabetic patients by 100% (2.8 vs 5.6%) and as a result underestimated bed occupancy by over 200% (4.3 vs 13.7%), and is thus failing to fulfil its potential as a demographic and epidemiological record of resource use by disease classification. PMID- 1600713 TI - Use of the accident and emergency department by patients with diabetes. AB - As part of a District-based audit of diabetes care all attendances (of diabetic and non-diabetic patients) at a local Accident and Emergency department were monitored over a 3-month period. A total of 9505 attendances took place of which 62 (0.7%) were by people with diabetes. This was no different from the expected number of attendances (61.5) based on the rates seen in non-diabetic individuals. Of these 62 attendances, 20 (by 15 individuals) were directly related to diabetes (hypoglycaemia 17, hyperglycaemia 1, for supplies of insulin or equipment 2). When these diabetes-specific attendances were removed from the total, the number of attendances (42) was significantly (p = 0.004) less than that expected. Diabetic males aged 0-19 years attended significantly more often than non diabetic individuals of the same age but this excess was solely attributable to diabetes. PMID- 1600714 TI - The diabetes annual review as an educational tool: assessment and learning integrated with care, screening, and audit. The North Tyneside Diabetes Team. AB - An integrated diabetes Annual Review is described, suitable for the long-term care of large numbers of diabetic patients. Equal weight is given to dietary and educational assessment as to medical care and screening. Based on well-developed team-work the patient moves through a structured review which culminates in goal setting and planned care for the subsequent year. A structured audit of the review was carried out on a cohort of 123 patients of whom 67 had had two annual reviews. Ten patients failed to attend. Knowledge scores improved by 44% between first and second reviews. In 34% of patients in the first year and in 46% in year two, HbA1c levels were outside a target range set for each treatment group, but only 18% had results outside target in both years. A postal questionnaire was returned by 74/108 (69%) patients. This indicated a high level of patient participation and satisfaction with the review process. The diabetes team set standards, conducted the review, and subsequently changed in-house working practices and documentation, and developed in-service training. PMID- 1600715 TI - Treatment of insulin lipohypertrophy with liposuction. PMID- 1600716 TI - Human insulin gone wrong. PMID- 1600717 TI - Hearing in large mammals: sound-localization acuity in cattle (Bos taurus) and goats (Capra hircus). AB - Sound localization acuity of 3 cattle (Bos taurus) and 2 goats (Capra hircus) was determined for brief complex sounds in a two-choice procedure. Thresholds around the median sagittal plane averaged 30 degrees and 18 degrees, respectively. For comparison, thresholds were obtained in the same test apparatus for humans (0.8 degrees) and a dog (8 degrees). Although the relatively poor acuity of cattle and goats compared with most mammals comes as some surprise, given their large interaural distances and the large binaural locus cues available to them, it is not unexpected when other factors are considered. Like other poor localizers (both domesticated and nondomesticated), cattle and goats are prey species with their best vision directed throughout nearly the entire horizon. In contrast to mammals with very narrow foveal fields, they may not need very accurate locus information from their auditory systems to direct their gaze to a sound source. PMID- 1600718 TI - Simultaneous conditioning in honeybees (Apis mellifera). AB - Honeybees (Apis mellifera) were classically conditioned with odor as conditioned stimulus (CS), sucrose as unconditioned stimulus (US), and proboscis extension as response. The purpose of Experiment 1 (Ns = 26 and 27) was to look for facilitation of forward conditioning by CS-US overlap, but rapid conditioning without overlap left little room for improvement. In 2 further experiments, CS and US were simultaneous, and response to odor alone was measured in subsequent tests. In Experiment 2, a Simultaneous group (N = 25) responded more to the training odor than did an Unpaired control group (N = 25). In Experiment 3, a differentially conditioned Simultaneous group (N = 29) responded more to an odor paired with sucrose in training (S+) than to an odor presented alone (S-). The implications of the results for the problem of the role of amount of reward in honeybee learning are considered. PMID- 1600719 TI - Development of self-recognition in chimpanzees (Pan troglodytes). AB - Chimpanzees (Pan troglodytes) demonstrate the ability to recognize themselves in mirrors, yet investigations of the development of self-recognition in chimpanzees are sparse. Twelve young chimpanzees, grouped by age, were given mirror exposure and tested for self-recognition and contingent movement. All 6 juveniles, 4 and 5 years old, exhibited mirror-guided, mark-directed behavior and clear evidence of self-recognition. In contrast, among the infants, only the oldest group of 2 1/2 year-olds exhibited clear evidence of self-recognition. All chimpanzees exhibited both self-directed behaviors and contingent movements. These results suggest that self-recognition occurs at a slightly older age in chimpanzees than in human infants. In humans, self-recognition is linked with other cognitive abilities. The results conform to the general pattern that great apes exhibit many cognitive skills comparable to those of 2-year-old humans. PMID- 1600720 TI - Differential sensitivity of Japanese macaques (Macaca fuscata) and humans (Homo sapiens) to peak position along a synthetic coo call continuum. AB - Difference limens (DLs) for changes in the temporal position of a pitch peak along a synthetic early-high to late-high coo continuum were measured in 2 Japanese macaques (Macaca fuscata) and 2 humans (Homo sapiens) in a low uncertainty, repeating standard discrimination procedure. Lowest DLs (19-32 ms for monkeys; less than 10 ms for humans) occurred near the endpoints of the continuum. Highest DLs (59-73 ms for monkeys; 25-27 ms for humans) occurred near the center of the continuum. DLs for both monkeys and humans corresponded to previously reported measures of temporal resolution. Neither monkeys nor humans exhibited categorical perception of the coo continuum, with a central area of enhanced sensitivity, a result previously reported by May, Moody, and Stebbins (1989) for similar stimuli. We conclude that our subjects discriminated variation in coo peak position by using general psychoacoustic mechanisms related to temporal discrimination. PMID- 1600721 TI - Relation between food preference and food-elicited vocalizations in golden lion tamarins (Leontopithecus rosalia). AB - We report the results of 2 studies on food-elicited vocalizations in golden lion tamarins (Leontopithecus rosalia). First, we investigated the preferences of 10 golden lion tamarins for 6 foods. Tamarins prefer mealworms and raisins significantly more than apple, egg, carrot, or marmoset diet. Food preference rank was significantly and positively correlated with the rank of latency to choose a particular food. Second, we investigated the relation between food preference and 15 vocal parameters measured from the calls emitted by 5 tamarins to a subset of the foods. Only 1 parameter was significantly correlated with food preference across animals. Within-subjects multivariate analysis of variance showed that the vocalizations to foods are significantly different. Our results support an hypothesis that food-elicited vocalizations vary in ways that correspond to the caller's preference but not in a manner that labels food type. PMID- 1600722 TI - Selection for conditionability in Drosophila melanogaster. AB - Successful bidirectional selective breeding of Drosophila melanogaster for excitatory conditionability is reported, using the reliable measures of individual differences (first described by Holliday & Hirsch, 1984, 1986a, 1986b) to test 1,324 animals. Bidirectional selective breeding for good and poor conditioning has produced, respectively, one population in which the percentage of animals showing good conditioning has increased over 25 generations from 19% to 77% and another in which it has decreased over 23 generations to 0%-4%. No increase in a measure of sensitization induced by an unconditioned stimulus (the central excitatory state) accompanied the increase in the percentage of good conditioners in the population selected for good conditioning, whose level of conditioned responding exceeds that of the sensitization measure. PMID- 1600723 TI - Are there preexisting behavioral characteristics that predict the dominant status of male NIH Swiss mice (Mus musculus)? AB - The behavior of isolated Cr:NIH(S) mice (Mus musculus) was studied in a holeboard test of exploration, in a plus-maze test of anxiety, in the resident-intruder paradigm of aggression, and in the swim test. Thereafter, mice that were matched for body weight were housed together in groups of 4-5. Within a week, 1 mouse per cage (the alpha) had attacked all its subordinate cagemates but lacked any signs of attack itself. Subordinate mice had bite marks on their tails and backs. When mice were isolated, no differences were found between the behavior of those that later became alphas and those that became subordinates. In contrast, after the establishment of the social hierarchy, alpha mice spent less time immobile in the swim test and had higher locomotor activities than did the subordinate mice. The results suggest that the differences in behavior between the alpha and subordinate mice result from aggressive social interactions in the home cage. PMID- 1600724 TI - [History and education of nursing as seen in 'Kyoiku Zasshi' (Education Periodical)]. PMID- 1600725 TI - [Nursing and welfare: where both meet and overlap]. PMID- 1600726 TI - [A visit to Florence Nightingale's birthplace]. PMID- 1600727 TI - [Asking about 'nursing and medicine']. PMID- 1600728 TI - [Toward better nursing, Symposium (Society for the Study of Scientific Nursing)]. PMID- 1600729 TI - [The world of Hildegard von Bingen]. PMID- 1600730 TI - [Searching for logic of children's recognition]. PMID- 1600731 TI - [What is psychiatry?]. PMID- 1600732 TI - Systemic quinine photosensitivity with photoepicutaneous cross-reactivity to quinidine. AB - A 75-year-old man developed an eczematous eruption on the face and dorsal aspects of the hands one July after 3 weeks' treatment with quinine, 0.25 g nightly, for nocturnal leg cramps. The photoreaction cleared within a week of quinine being stopped. UVA and UVB erythema threshold determinations, after the acute episode had subsided, were normal. A photopatch test was positive for irradiated quinine down to a concentration of 0.01% and for unirradiated quinine to 0.5%. The test with the isomer quinidine was positive only when irradiated, down to a concentration of 0.01%. Preirradiated samples of quinine and quinidine were negative. Whereas in contact allergy quinine and quinidine usually do not cross react, after systemic photosensitization, the 2 isomers probably form a common photoproduct, accounting for the cross-reactivity. PMID- 1600733 TI - Evaluation of a self-administered questionnaire on hand dermatitis. AB - The purpose of the study was to evaluate a self-administered questionnaire on hand dermatitis that was developed to identify persons with hand dermatitis in epidemiological studies. A total of 109 nurses were subject to dermatological examination of the hands within 1 month of returning the questionnaire. 2 types of questionnaire diagnoses were made: a 'symptom-based' diagnosis and a 'self reported diagnosis'. These were compared to the medical diagnosis of hand dermatitis. The prevalence of hand dermatitis in the 12 months before the study, based on the medical diagnosis, was 18.3%. The prevalence according to the symptom-based diagnosis and the self-reported diagnosis was 47.7% and 17.4%, respectively. The sensitivity and specificity of the symptom-based diagnosis were 100% and 64%, respectively. It is concluded that the symptom-based diagnosis can be used as screening instrument for the detection of cases in large study populations, if followed by dermatological examination of persons with a positive diagnosis. The sensitivity and specificity of the self-reported diagnosis were 65% and 93%, respectively. It is concluded that the self-reported diagnosis can be used to obtain a rough estimate of the prevalence, although comparison of prevalence figures between study populations may be distorted due to a difference in reporting of hand dermatitis. The results of the study illustrate the size of the differences in prevalence estimates that may arise as a result of differences in the definition and method of diagnosing hand dermatitis. PMID- 1600734 TI - Keratinocyte expression of class II MHC antigens in long-lasting allergic patch test reactions. AB - The keratinocyte expression of class II MHC antigens HLA-DR, DP and DQ was studied in 20 long-lasting allergic patch test reactions and 17 normal allergic patch tests reactions. No significant difference in the expression of these antigens in the 2 groups was detected. No 1 allergen was responsible for the majority of long-lasting allergic patch test reactions. The immunological mechanisms which may contribute to long-lasting allergic patch test reactions are discussed with reference to HLA-DR keratinocytes. PMID- 1600735 TI - Evaluation of contact allergy to chemicals using laser Doppler flowmetry (LDF) technique. AB - Skin blood flow in allergic contact reactions and cross-sensitivity were evaluated using laser Doppler flowmetry (LDF) to study the dose-response relationships in phases of induction and challenge in guinea pigs. Guinea pigs were sensitized with different doses of 1-chloro-2,4-dinitrobenzene (DNCB) and challenged with different doses of DNCB and 2,4-dinitrobenzene sulfonic sodium salt (DNBS). The skin reactions were evaluated by LDF and visual reading score. The results indicated that there were dose-response relationships between the doses of DNCB and LDF measurements in both phases of induction and challenge, that there was a cross-reaction between DNCB and DNBS, and that the reactions at 24 h were greater than that at 48 h after removal of the patches. LDF may discriminate between positive patch test reactions and negative or doubtful reactions, but not between weak positive and strong positive reactions. This is because vascular dilatation and increase of flow already reaches a maximum in weak reactions. The more advanced phases are dominated by oedema formation. This is simply the nature of the inflammatory reaction, rather than a methodological error. The important point is that LDF can separate positive reactions from negative/uncertain reactions. The results indicated that LDF, as a non-invasive technique, may objectively and quantitatively evaluate the dose-response relationships of contact sensitivity of sensitizers. PMID- 1600736 TI - Propolis allergy (IV). Studies with further sensitizers from propolis and constituents common to propolis, poplar buds and balsam of Peru. AB - 26 different compounds have been investigated experimentally for their sensitizing capacity in guinea pigs. 19 of these occur in propolis as well as in poplar bud exudates, and 14 of them are also found in balsam of Peru. 4 caffeates and benzyl isoferulate were found to be strong sensitizers. 7 compounds were moderate, and 13 compounds showed only weak sensitizing potency. Methyl cinnamate was negative. Patch tests in 11 propolis-sensitive patients once more revealed 3 methyl-2-butenyl caffeate and phenylethyl caffeate as the major sensitizers. In addition to the 8 compounds already known to occur in propolis as well as in balsam of Peru, we detected 5 further substances that both materials have in common. Among these, benzyl isoferulate is considered a noteworthy sensitizer. Coniferyl benzoate, which was shown to be a moderate sensitizer, is present in fresh samples of balsam of Peru, while in propolis it has been detected only once so far. The flavonoid aglycones occurring in poplar bud exudates, and hence also in propolis, are weak sensitizers which play only a minor role in propolis hypersensitivity. PMID- 1600737 TI - Allergic contact dermatitis due to shoes in children: a 5-year follow-up. PMID- 1600738 TI - Pacemaker dermatitis. PMID- 1600739 TI - Influence of topically applied cyclosporin A in various vehicles on patch test reactions. PMID- 1600740 TI - Allergic contact dermatitis from minoxidil. PMID- 1600741 TI - Contact dermatitis from Euxyl K 400 in cucumber eye gel. PMID- 1600742 TI - Contact dermatitis from a Dalbergia nigra bracelet. PMID- 1600743 TI - Patch test preparations of metallic mercury under the microscope. PMID- 1600744 TI - Sensitization to chloramphenicol. PMID- 1600745 TI - The secretory granule and the mechanism of stimulus-secretion coupling. PMID- 1600746 TI - Activation of cholera toxin by ADP-ribosylation factors, 20-kDa guanine nucleotide-binding proteins. PMID- 1600747 TI - RNA virus populations as quasispecies. AB - RNA virus mutation frequencies generally approach maximum tolerable levels, and create complex indeterminate quasispecies populations in infected hosts. This usually favors extreme rates of evolution, although periods of relative stasis or equilibrium, punctuated by rapid change may also occur (as for other life forms). Because complex quasispecies populations of RNA viruses arise probabilistically and differentially in every host, their compositions and exact roles in disease pathogenesis are indeterminate and their directions of evolution, and the nature and timing of "new" virus outbreaks are unpredictable. PMID- 1600748 TI - Genetic diversity of RNA viruses. PMID- 1600749 TI - Emergence and transmission of influenza A viruses resistant to amantadine and rimantadine. AB - Amantadine- and rimantadine-resistant viruses have been recovered from approximately 30% of patients treated for acute H3N2 subtype influenza and less often from their close contacts receiving drug prophylaxis. The limited data suggest that resistant viruses can emerge rapidly during drug therapy, as early as 2-3 days into treatment. These viruses retain their resistance phenotype during multiple passages in the laboratory and appear to be genetically stable in this regard. Studies in families and in nursing homes indicate that resistant isolates appear to be transmissible from treated patients and cause typical influenza in contacts receiving drug prophylaxis. It is unknown whether resistant human viruses are capable of competing with wild-type ones during multiple cycles of infection in the absence of the drug. These viruses appear to be pathogenic, and no evidence indicates that they differ from wild-type strains. Thus, these viruses clearly possess the biologic properties that are associated with clinically important drug resistance. However, limited information is available to assess their actual impact. It is unknown what degree of selective drug pressure would be required to cause substantial transmission of resistant viruses during community outbreaks. Natural selection of antigenic variants and disappearance of previous variants may prevent the emergence of viruses that have been altered in the genes coding both for the surface glycoproteins and for the M2 protein. However, the emergence of drug-resistant influenza viruses appears to pose potential clinical problems in certain epidemiologic situations involving close contact with treated patients. PMID- 1600750 TI - Selection of zidovudine-resistant variants of human immunodeficiency virus by therapy. PMID- 1600751 TI - Genetic diversity and evolution of retroviruses. PMID- 1600752 TI - Human immunodeficiency virus type 1 quasispecies in vivo and ex vivo. PMID- 1600753 TI - Genetic recombination in RNA viruses. PMID- 1600754 TI - Replication and evolution of viroid-like pathogens. PMID- 1600755 TI - Mutations and A/I hypermutations in measles virus persistent infections. PMID- 1600756 TI - Evolutionary processes in influenza viruses: divergence, rapid evolution, and stasis. PMID- 1600757 TI - The ACCP-SCCM consensus conference on sepsis and organ failure. PMID- 1600758 TI - The management of long-term mechanical ventilation at home. PMID- 1600760 TI - The oxygen cost of breathing. PMID- 1600759 TI - Intracoronary thrombolysis. PMID- 1600761 TI - Weaning is demeaning. It's time for liberation! PMID- 1600762 TI - Disturbance of pulmonary gas exchange in patients with right ventricular infarction. AB - To evaluate the difference in pulmonary gas exchange in patients with and without right ventricular infarction, 147 consecutive patients with their first inferior wall Q-wave acute myocardial infarction were studied. Thirty-nine patients (group 1) had electrocardiographic evidence of right ventricular infarction and it was absent in 108 patients (group 2). A significantly wider alveolar arterial oxygen difference and higher roentgenographic scores were observed in group 1 compared with group 2. Although there were no significant differences in pulmonary artery wedge pressure and colloid osmotic pressure between groups 1 and 2, mean right atrial pressure was significantly higher, while cardiac output and mixed venous oxygen saturation were lower in group 1 compared with group 2. Patients in group 1 had significantly more left ventricular segments with advanced asynergy and higher incidence of proximal right coronary artery lesions than those in group 2. Thus, our data suggest that disorder of pulmonary gas exchange in patients with right ventricular infarction may be explained by increased permeability of the alveolar capillary membrane secondary to larger extent of ischemic myocardium and by hemodynamic abnormalities associated with right ventricular infarction. PMID- 1600763 TI - Exposure of health care workers to aerosolized pentamidine. AB - In patients, urinary levels of pentamidine have been shown to reflect pulmonary deposition of aerosolized drug. Using urinary levels and air filter samples, we assessed factors responsible for health care worker (HCW) exposure. We measured serial urine samples in HCWs who administered aerosol pentamidine over an 11 month period and compared them with serial urine levels measured over 30 days in a normal volunteer in whose lungs a known amount of pentamidine (3.39 mg) had been deposited. Ambient exposure to pentamidine was determined by continuous high volume air sampling in the treatment room during routine therapy. In addition, the amount of pentamidine released by six HIV-positive subjects, performing tidal breathing with a Respirgard II nebulizer in an airtight booth, was measured by extracting air from the booth through a filter. The effect of adding noseclips, of coughing (with nebulizer shut down), and of removing the nebulizer from the patient's mouth without turning it off, were determined. Pentamidine in the urine of the normal volunteer reached a peak concentration of 9.5 ng/mg creatinine/ml and was detectable for 30 days following the exposure. In HCWs, pentamidine was detected intermittently in four of five individuals with levels as high as 18.2 ng/mg creatinine/ml. Samples of ambient treatment room air indicated small daily releases of pentamidine (0.013 +/- 0.02 mg per patient treated), but simultaneous urine levels in HCWs were negative. The data from the airtight booth revealed that removing the nebulizer from a patient's mouth without turning it off caused a 360-fold increased in pentamidine release compared to tidal breathing. Coughing resulted in a 6.9 (range 0.9-14.2)-fold increase in release, while the addition of noseclips had no significant effect. The pattern of intermittently positive urine tests and the low levels of ambient pentamidine detected in the air of the treatment room suggest that HCWs are being exposed to episodic but high concentrations of pentamidine. High level exposure is most likely to occur during treatment interruptions which are usually precipitated by coughing episodes. Because of the intermittent pattern of exposure and slow clearance of pentamidine, urine assay is useful for detecting high intermittent exposure. Random air sampling is a sensitive indicator of low level exposures but may not detect episodic high level releases. PMID- 1600764 TI - Hypoventilation and apnea in children during mechanically assisted ventilation. AB - Uncuffed tracheostomy tubes are used for long-term mechanical ventilation in children. However, upper airway mechanics differ between sleep and wakefulness; this may affect air leak around tracheostomies. We studied 19 children with high cervical spinal cord injury on portable positive pressure ventilators, age range birth to 19 years. Ventilator settings were adjusted while awake to achieve PaCO2 less than 45 mm Hg and PO2 greater than 90 mm Hg. Clinically several children with uncuffed tracheostomies became unstable at night with seizures and sleep disruption. Nine of 11 children on volume controlled systems were found to be inadequately ventilated during sleep. Substitution with a cuffed tracheostomy allowed adequate ventilation both awake and asleep, suggesting that inadequate ventilation during sleep was due to an uncompensated leak around the uncuffed tracheostomy. To avoid cuffed tracheostomies, eight children received pressure controlled ventilation. Gas exchange was adequate throughout the day and night. We conclude that children receiving volume controlled mechanical ventilation via uncuffed tracheostomy tubes can exhibit hypoventilation due to uncompensated air leak. Pressure controlled ventilation improves adequacy of gas exchange during sleep and wakefulness. PMID- 1600765 TI - Pulmonary embolism in younger adults. AB - To test the hypothesis that the clinical presentation and outcomes are different when pulmonary embolism occurs in younger (age 18 to 40 years) as compared to older (age greater than 40 years) adults, 40 younger patients were compared with older patients. No risk factors could be identified in 28 percent of the younger group. Normal physical examinations were more common (58 vs 28 percent, p = 0.01) among younger as compared with older adults. Hypoxemia was absent in 29 percent of the younger and 3 percent of the older group (p = 0.004); P(A-a)O2 was significantly lower among younger patients even after controlling for age. Mortality was decreased sevenfold (2.5 vs 18 percent, p = 0.03) among younger patients. These data indicate that pulmonary embolism tends to have a subtle presentation in younger adults. When diagnosed and treated, the mortality rate is substantially less among younger as compared with older patients. PMID- 1600766 TI - Cardiac catheterization through the internal jugular vein in pediatric patients. An alternative to the usual femoral vein access. AB - The percutaneous femoral vein approach is used routinely for cardiac catheterization in the pediatric age but in some children, it may be impossible as in the case of iliac vein or inferior vena cava thrombosis due to previous cardiac catheterization, or inconvenient as for right ventricular endomyocardial biopsies. In the period between 1982 and 1990, 160 cardiac catheterizations or right ventricular endomyocardial biopsies were performed in 102 children. Patients ranged in age between 2 months and 17 years (mean, 3.8 years) and in weight from 3.2 to 57.3 kg (mean, 14.4 kg). Indications for the internal jugular vein approach were as follows: (1) thrombosis of the inferior vena cava due to previous cardiac catheterization in 42 patients (41 percent); (2) right ventricular endomyocardial biopsy after cardiac transplant in 19 patients (19 percent); (3) control catheterization of the pulmonary arteries following classic or bidirectional cavopulmonary anastomosis in 16 patients (16 percent); (4) superior vena cava obstruction following Mustard's procedure in 14 patients (14 percent); (5) failed percutaneous femoral venous approach in six patients (6 percent); and (6) absence of the hepatic segment of the inferior vena cava in four patients (4 percent). The right or left internal jugular vein could be entered in all but three procedures (98 percent). Seventeen patients had more than one procedure through the same internal jugular vein and the vein was found patent in all. A complete right heart cardiac catheterization was performed using this route. Right ventricular endomyocardial biopsy and interventional procedure were performed through this route. Two major complications occurred. A patient developed a central transient ischemic attack and another patient developed a persistent Horner syndrome. Accidental carotid puncture occurred in five patients without consequences. Our data indicate that cardiac catheterization in infants and children can be performed safely through the internal jugular vein, with a high success rate and a low incidence of major complications. PMID- 1600767 TI - Detection of patent foramen ovale by contrast transesophageal echocardiography. AB - A series of 32 patients undergoing cardiac catheterization and/or operation to document the presence of patent foramen ovale (PFO) were studied. All were examined by contrast transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) during normal breathing and the Valsalva maneuver. A right to-left shunt at the atrial level was visualized by contrast TEE in 14 patients during normal breathing and in 20 patients during the Valsalva maneuver. In comparison, contrast TTE revealed this shunt in only eight patients during normal breathing and in 12 patients during the Valsalva maneuver. All of the foramina proved to be patent by contrast TTE were also found by contrast TEE. All but one (19 of 20) patients, shown to have PFO by contrast TEE, could be confirmed at cardiac catheterization and/or operation. Using cardiac catheterization and/or operation as a gold standard, contrast TEE appears to be a more sensitive (100 percent vs 63 percent, p less than 0.005) and accurate (97 percent vs 78 percent, p less than 0.05) method than contrast TTE in the detection of PFO. PMID- 1600768 TI - Esophageal function and gastroesophageal reflux during sleep and waking in patients with chronic obstructive pulmonary disease. AB - This study was conducted to assess esophageal function and pulmonary resistance changes with esophageal acidification in patients with COPD. Twelve patients with COPD and a mean age of 55.6 years were studied. Each patient underwent standard esophageal manometry, 24-h ambulatory pH testing, esophageal acid clearance evaluation during sleep, and an assessment of pulmonary resistance with and without esophageal acid perfusion. Neither airway resistance nor conductance was altered by the esophageal acid infusion; LES pressures were normal and esophageal contractile pressures were mildly decreased. Acid exposure in the upright and supine positions was within normal limits. Acid clearance during sleep was similar to that in normal subjects; however, acid clearance during waking appeared to be somewhat prolonged in the COPD patients. We conclude that patients with COPD do not have a bronchoconstrictive reflex to distal esophageal acidification, and esophageal function in these patients appears to be relatively normal. PMID- 1600769 TI - The acute effects of continuous positive airway pressure and oxygen administration on blood pressure during obstructive sleep apnea. AB - We have measured blood pressure continuously with a digital artery blood pressure monitor in eight patients with severe obstructive sleep apnea (OSA) during 30 min each of wakefulness, OSA, OSA with added oxygen to keep saturation above 96 percent at all times (OSA+O2), and nasal continuous positive airway pressure (CPAP) therapy. Mean blood pressures were not different between wakefulness, OSA, OSA+O2, and CPAP, although the variability in blood pressure was significantly greater during OSA and OSA+O2 than during wakefulness and CPAP. The addition of oxygen did not attenuate the variability in blood pressure. Using multiple linear regression modeling to further dissect out the principal variables determining the postapneic blood pressure rise, we found that only apnea length (r2 = 0.28, p less than 0.0001) and pulse rate changes (r2 = 0.15, p less than 0.0001) remained significantly related to SBPmax, while hypoxemia did not. We found the same trends in the other variables SBPten, DBPmax, and DBPten. Hypoxemia made a small contribution to the size of DBPmax, although this was small by comparison with apnea length. We conclude that CPAP treatment of OSA does not lower mean blood pressure acutely, although it significantly reduces the large oscillations in blood pressure seen in patients with untreated OSA. The rise in blood pressure following each apnea is not primarily due to arterial desaturation but is related to apnea length and may be caused by increased sympathetic activity secondary to arousal. PMID- 1600770 TI - Acute exacerbations in severe COLD patients. Treatment using positive pressure ventilation by nasal mask. AB - We retrospectively evaluated the clinical effectiveness of a treatment schedule with intermittent positive pressure ventilation via nasal mask in 49 patients with acute exacerbations of COLD. According to the ability to successfully tolerate a preliminary trial with NIPPV, patients were submitted either to standard treatment plus NIPPV (25 patients) or to ST alone (24 patients). The ST consisted of medical, oxygen and physical therapy. The NIPPV was delivered by a volume cycled ventilator in control mode at least 4 h a day for five consecutive days a week, for three weeks. Comparison of baseline with measurements performed after 10 and 21 days of treatment respectively showed a significant improvement in PaO2 and in PaCO2 in both groups. After 21 days of treatment, VC, FEV1, inspiratory muscle strength, and dyspnea significantly improved in both groups. No significant difference was found between groups at any time of treatment. We conclude that the treatment schedule of NIPPV used is not more effective than ST alone in acute exacerbations of COLD. PMID- 1600771 TI - Nasal CPAP reduces gastroesophageal reflux in obstructive sleep apnea syndrome. AB - Anecdotal reports suggest that obstructive sleep apnea syndrome (OSAS) patients may suffer from frequent nocturnal gastroesophageal reflux (GER) and that nasal continuous positive airway pressure may be an effective form of antireflux therapy in this population. To confirm these clinical impressions, we performed two consecutive days of 24-h esophageal pH monitoring, nocturnal esophageal pressure recording, and polysomnography on six OSAS patients complaining of regular nocturnal GER. On night one, the patients were untreated. Five of six subjects had abnormal amounts of nocturnal GER. Arousal, movement and swallowing were more frequent (p less than 0.043) and nadir intrathoracic pressure lower (p less than 0.005) in the 30 s prior to precipitous drops in esophageal pH (greater than or equal to 2 pH units) than during random control periods. A direct association between obstructive apneas and GER was not identified. On night two, nasal CPAP was administered and successfully treated apnea in five of six subjects. In these patients, there was also dramatic reduction in GER frequency and duration on CPAP. The mean percentage of time pH less than 4 dropped from 6.3 +/- 2.1 to 0.1 +/- 0.1 percent (p less than 0.025). We believe that OSAS may predispose to nocturnal GER by lowering intrathoracic pressure and increasing arousal and movement frequency. Nasal CPAP can correct these predisposing factors and reduce GER. PMID- 1600772 TI - Utilization of acute bronchodilator responses in stable COPD to predict the relative efficacy of individual agents. AB - A survey of four inhaled beta-agonist agents was evaluated as a means of selecting the optimum agent for chronic therapy in patients with stable COPD. Eighteen patients completed as protocol of prebronchodilator and postbronchodilator spirometry utilizing albuterol, metaproterenol, pirbuterol, and terbutaline daily in random order. Subsequently, each patient received treatment with either the greatest or least response-invoking agent for four weeks, followed by a second interval with the opposite agent. At the end of each interval, the results of repeat spirometry, arterial blood gas determinations, 12 min walks, dyspnea questionnaires, and self-monitored peak expiratory flow rates were recorded. Use of the greatest response-invoking agent resulted in significantly larger prebronchodilator and postbronchodilator FEV1 and FVC. No other study factor was significantly different. Acute bronchodilator surveys may have a role in medication selection in view of the improvement in spirometric volumes. PMID- 1600773 TI - Surfactant analysis during Pneumocystis carinii pneumonia in HIV-infected patients. AB - Pulmonary surfactant is altered in experimental Pneumocystis carinii pneumonia. Although P carinii is a major causative agent of pneumonia in immunocompromised patients, the pathophysiology of lung injury caused by this organism is poorly understood. Therefore, we studied bronchoalveolar lavage specimens obtained from 19 HIV-infected subjects with PCP compared with specimens from ten healthy control subjects. As iterative BAL was performed, 37 BAL specimens were analyzed for protein and phospholipid. The BAL samples were divided into two groups as follows: 22 BAL samples with the presence of P carinii and 15 BAL samples without P carinii. Compared to control subjects, HIV+ BAL presented a significant increase of PR and a decrease of total PL in both P carinii+ and P carinii- BAL, but in P carinii+ BAL, the fall of PL/PR ratio was significantly more pronounced compared to P carinii- (0.09 +/- 0.02 vs 0.19 +/- 0.04, p less than 0.02). The BAL performed during the recovery of PCP showed an improvement of initial biochemical abnormalities. Surfactant composition was also altered, with a phosphatidylcholine and phosphatidylglycerol drop and a sphingomyelin and lysophosphatidylcholine increase. The presence, even in P carinii- BAL, of less polar compounds of undetermined nature, was revealed. We concluded that in HIV+ patients, abnormalities of pulmonary surfactant were present before PCP, and that the development of PCP enhances these abnormalities. These surfactant alterations may contribute to the saprophyte-pathogen transformation of P carinii, but this hypothesis requires further investigation that is presently in progress. PMID- 1600774 TI - Lung function and bronchial responsiveness after bronchoalveolar lavage and bronchial biopsy performed without premedication in stable asthmatic subjects. AB - We evaluated tolerance, safety, and effects on lung function and bronchial responsiveness of BAL (4 x 50 ml) combined with BB (three to five specimens) performed without premedication in 13 mild and stable asthmatics and eight healthy volunteers. All subjects tolerated bronchoscopy procedures well and without serious side effects. During procedures, no supplemental oxygen was administered and no ECG abnormalities were noted. The PEFR was measured before and immediately after bronchoscopy and at 5-min intervals up until recovery. The maximal percentage fall in PEFR after bronchoscopy was significantly greater in asthmatics (23.1 +/- 13.9 percent) compared to normal subjects (7.8 +/- 8.2 percent, p less than 0.01). Changes in PEFR returned to baseline values within 120 min in all asthmatics. The tcPO2 was recorded at baseline, during and after bronchoscopy. In both groups, a significant change in tcPO2 was measured during the infusion of BAL aliquots, and persisted throughout the procedure. A significant difference in asthmatics compared to healthy subjects was evident during BB and at the end of the procedure (p less than 0.05). In asthmatics, M challenge was performed on three different days over a three-week period prior to bronchoscopy, and was repeated at intervals of 2, 6, and 24 h following procedure. The PC20 M values measured before bronchoscopy were found to have a very high reproducibility (intraclass correlation coefficient = 0.93). The PC20 values measured during experiment times after bronchoscopy were not significantly different from baseline values. These data demonstrate that in mild and stable asthmatics, BAL combined with BB can be safely performed following administration of only local anesthesia. In carefully selected asthmatic subjects, transient bronchoconstriction and a lowering of oxygen tension can be induced by BAL and BB, whereas changes in bronchial responsiveness are more unlikely to occur. PMID- 1600775 TI - Combined effect of smoking habits and occupational exposure to hard metal on total IgE antibodies. AB - A survey was made within a population of workers (n = 706) exposed to hard metal dust (an alloy including cobalt), an agent known to cause occupational allergy. Twenty-seven (4 percent) of 733 workers were eliminated from consideration in this study because of atopic status identified prior to starting work in the plant. Using a Phadebas PRIST, the subjects' total IgE levels were determined and related to their smoking and exposure status. Nonexposed male smokers (n = 135) had a higher geometric mean IgE level (39.7 IU/ml) than did nonexposed subjects who had never smoked (33.1 IU/ml; n = 99); those with a higher Brinkman index (greater than 300), a smoking index obtained by multiplying the number of cigarettes per day by the duration of smoking in years, had significantly (p less than 0.05) decreased IgE levels. Although ex-smokers (n = 72) had a higher geometric mean IgE level (73.3 IU/ml) than did those who had never smoked, their serum IgE level declined with age since the time they quit smoking, regardless of their hard metal exposure status. Hard metal (cobalt) exposure may play a significant role as an adjuvant in the production of total IgE. A multivariate analysis demonstrated that hard metal exposure and a smoking habit together arithmetically (p less than 0.05) increased total IgE levels. These two factors may be preventable risk factors for occupational allergy in hard metal workers. PMID- 1600776 TI - Transdermal scopolamine as treatment of bradyarrhythmias. AB - Fifteen patients with different degrees of chronic bradyarrhythmias of supraventricular origin were studied with Holter monitoring before and during application of a transdermal patch of scopolamine. No changes were found in the mean or minimal heart rates, standard deviation of the RR interval, or the degree of bradyarrhythmia. It is concluded that transdermal scopolamine is not an adequate treatment of chronic symptomatic bradyarrhythmias. PMID- 1600777 TI - Exercise performance in patients with uncomplicated essential hypertension. Effects of nifedipine-induced acute blood pressure reduction. AB - In untreated patients with uncomplicated essential hypertension, exercise induces an abnormal increase in blood pressure; the influences of this increase on exercise were evaluated by a cardiopulmonary exercise test (CPX) performed in control conditions (step 1) and during acute blood pressure reduction (step 2). Patients were classified as (1) normotensive (resting diastolic blood pressure [BPd] less than 90 mm Hg; n = 14), (2) mildly hypertensive (BPd of 90 to 104 mm Hg; n = 9), and (3) moderately to severely hypertensive (BPd greater than or equal to 105 mm Hg; n = 16). For the three groups, peak mean blood pressure during exercise was 125 +/- 5 mm Hg (mean +/- SEM), 144 +/- 3 mm Hg (p less than 0.01 vs normotensive), and 161 +/- 4 mm Hg (p less than 0.01 vs normotensive and p less than 0.01 vs mild hypertension), respectively. Oxygen consumption (VO2) at peak exercise and at ventilatory anaerobic threshold was 26.1 +/- 1.1 and 17.2 +/ 0.5 ml/min/kg, 25.4 +/- 1.1 and 16.9 +/- 0.8 ml/min/kg, and 26.4 +/- 1.3 and 17.5 +/- 1.2 ml/min/kg in normotensive subjects, those with mild hypertension, and those with moderate to severe hypertension, respectively. Fourteen normotensive subjects, six with mild hypertension, and nine with moderate to severe hypertension participated to step 2 (nifedipine vs placebo, double-blind crossover). Nifedipine reduced blood pressure at rest and at peak exercise in those with hypertension. Peak exercise VO2 was unaffected by nifedipine in both normotensive subjects and those with hypertension. With nifedipine, ventilatory anaerobic threshold occurred earlier and at a lower VO2 in mild and in moderate to severe hypertension (delta VO2 = -1.9 and -2.4 ml/min/kg, respectively). These findings might be due to nifedipine-induced redistribution of blood flow during exercise and might be the reason for the complaint of weakness after blood pressure reduction in hypertensive subjects. PMID- 1600778 TI - Platelet imaging of thromboembolism. Natural history of postoperative deep venous thrombosis and pulmonary embolism illustrated using the 111In-labelled platelet specific monoclonal antibody, P256. AB - BACKGROUND: Deep venous thrombosis (DVT) and pulmonary thromboembolic disease are difficult to diagnose, particularly following surgery. This report demonstrates the use of 111In-labelled platelet-specific monoclonal antibody, P256 Fab', for the diagnosis and study of the time course of thromboembolic disease in a patient following total hip replacement. METHOD: One hundred micrograms of pentetic acid (DTPA)-P256 Fab' was labelled with 8 to 10 MBq of 111In chloride by incubation at room temperature for 15 min. After dilution in physiologic saline, the tracer was injected intravenously on the third and sixth days postoperatively. Imaging of the chest, pelvis, and legs was carried out at 24, 48 and 72 h following each injection. RESULTS: The first image four days after surgery demonstrated activity in the right heart which moved to the right pulmonary artery on the following day. Activity was seen in both femoral veins; on the left, this increased over two days, followed by a reduction on the seventh day after surgery, at which time new activity was seen in the right heart. After a further two days, this activity moved to the left pulmonary artery. The DVT was confirmed by venography and the pulmonary embolism (PE) by ventilation perfusion scan. CONCLUSIONS: 111Indium labelled platelet-specific monoclonal antibody, P256 Fab', provides a technique for studying the natural history of thromboembolic disease and its treatment. PMID- 1600779 TI - Carbon dioxide and oxygen partial pressure in expiratory water condensate are equivalent to mixed expired carbon dioxide and oxygen. AB - This study was to determine whether the PCONCO2 and PCONO2 which collect in the expiratory trap of a ventilator circuit are equivalent to PECO2 and PEO2. Fifty studies were performed in 34 mechanically ventilated male patients. Five milliliters of condensate fluid were collected and PECO2 and PEO2 were measured. Exhaled gases were collected simultaneously with condensate fluid for 5 min in a meteorologic balloon and FECO2 and FEO2 were measured; PECO2 and PEO2 were then calculated. The mean PECO2 was not significantly different from PCONCO2 nor was the PCONO2 significantly different from the condensate PCONO2. There was a high correlation between mixed expired PECO2 and PCONCO2 as well as PEO2 and PCONO2. These data indicate expiratory PCONCO2 and PCONO2 provide a valid reflection of PECO2 and PEO2. The PCONCO2 and PCONO2 measured in a clinical blood gas analyzer are accurate and may be used in calculation of VD/VT and in metabolic assessments. PMID- 1600780 TI - Mycobacterium avium complex pulmonary disease presenting as an isolated lingular or middle lobe pattern. The Lady Windermere syndrome. AB - BACKGROUND: Pulmonary disease due to Mycobacterium avium complex (MAC-PD) radiographically resembles that due to tuberculosis; it preferentially affects elderly white men with predisposing pulmonary disorders (PDPD). METHODS: Twenty nine patients with MAC-PD were identified from a community-based population, and the medical records and chest roentgenograms (CRs) of six with a previously undescribed pattern of MAC-PD were reviewed. The distinctive clinical and demographic features of these six patients were identified and summarized. RESULTS: All were women who tended to be elderly. None had clinically evident PDPD. The dependent portion of the lingula or its counterpart, the middle lobe, was initially affected. Hilar adenopathy, volume loss, and cavitary disease were uniformly absent. CONCLUSIONS: To account for the distinctive features of this syndrome, we offer the hypothesis that habitual voluntary suppression of cough may have led to the development of nonspecific inflammatory processes in these poorly draining lung regions, upon which MAC-PD engrafted. We offer the term, Lady Windermere's syndrome, to describe this pattern among elderly women and to suggest that their fastidiousness may be its root cause. PMID- 1600782 TI - Tracheobronchial clearance in patients with pulmonary sarcoidosis. AB - Lung mucociliary clearance was measured using an objective, noninvasive radioaerosol technique in 13 patients with pulmonary sarcoidosis and 13 matched, healthy control subjects. Four of the sarcoid patients had never received any steroid therapy, five were currently receiving oral corticosteroids, and the remaining four were using inhaled corticosteroids only. A statistically significant retardation in tracheobronchial clearance (p less than 0.02) was observed in the sarcoid patients compared to the control subjects. The sarcoid patients using inhaled corticosteroids appeared to demonstrate the greatest degree of mucociliary transport impairment. The sarcoid patients in apparent remission and those receiving oral corticosteroid therapy had clearances better than those using inhaled corticosteroids, but they were still reduced compared to the control subjects. This study demonstrates that lung mucociliary clearance is adversely affected in patients with pulmonary sarcoidosis and raises the question of the possible consequences that could follow long-term inhaled immunosuppressive therapy on the prime clearance defense mechanism within the human lungs. PMID- 1600781 TI - Bronchogenic carcinoma in patients with pulmonary histiocytosis X. AB - Five cases of bronchogenic carcinoma were observed among 93 patients with pulmonary histiocytosis X (Hx). Mean age at the time of diagnosis of Hx was 42 years; on the average, cancer occurred 10.5 years later. All patients were smokers and continued to smoke heavily at the time of diagnosis of cancer. Comparison of the five cases associating Hx and lung carcinoma with a group of 88 control patients suffering from Hx alone suggested that smoking played the predominant role in the pathogenesis of cancer. In fact, among the four patients with Hx and carcinoma older than 45 years, tobacco consumption was significantly greater (64.7 +/- 37 pack-year, mean +/- SD) than that of the 15 control patients of the same age with only Hx (40.8 +/- 11.6, p less than 0.01). In light of this good correlation, the diagnosis of Hx strongly advocates stopping tobacco smoking and long-term medical follow-up. PMID- 1600783 TI - The dependency of oxygen consumption on oxygen delivery in critically ill postoperative patients is mimicked by variations in sedation. AB - The finding of a dependence of oxygen consumption on oxygen delivery in critically ill patients has encouraged interventions to increase oxygen delivery index (DO2I) to overcome tissue hypoxia. In individuals other factors may influence oxygen consumption index (VO2I) and DO2I and may cause an apparently dependent relationship. We studied the effects of sedation and temperature on the VO2I/DO2I relationship in 13 perioperative patients. Pooled data showed significant correlations between VO2I and DO2I (r greater than 0.6, p less than 0.05) but also between VO2I and sedation score (r greater than 0.7, p less than 0.05), but not VO2I and temperature (r less than 0.5). When VO2I was standardized for the effects of sedation score (SS), the relationship between VO2I and DO2I was lost (r less than 0.5). Seven of 13 patients had significant (p less than 0.05) correlations between VO2I and SS and six of 13 between VO2I and DO2I; when standardized for the effect of varying sedation, no relationships were significant. When interpreting oxygen transport data from critically ill patients, the effects of sedation but not temperature must be taken into account; otherwise a false impression of a dependent relationship between VO2I and DO2I may cause unnecessary treatment. PMID- 1600784 TI - Patterns of sedation and analgesia in the postoperative ICU patient. AB - Control of pain, discomfort, and agitation is an integral part of the postoperative management of critically ill patients. We examined the sedative and analgesic practices in a surgical ICU during two six-month periods, one in 1986 1987 and the other in 1989-1990. Narcotics, especially morphine and Fentanyl, were the most commonly used drugs. The amount of Fentanyl received by the endotracheal patients in the 1986-1987 group was quite large, 5.5 +/- 4.3 (SD) mg/day. The use of midazolam during the second survey period was associated with a reduced dose of narcotics in artificially ventilated patients receiving continuous intravenous Fentanyl and morphine. The use of epidural Fentanyl, especially following thoracic surgery, was greatly increased during the second study period. More work is needed to assess the effects and effectiveness of ICU sedative and analgesic regimens. PMID- 1600785 TI - Vascular erosion by central venous catheters. Clinical features and outcome. AB - We evaluated the clinical characteristics of eight patients who presented with vascular erosion from central venous catheters and reviewed the available literature. Patients typically presented with dyspnea or chest pain, unilateral or bilateral pleural effusions, and mediastinal widening one to seven days after catheter insertion. Pleural fluid appeared transudative with variable glucose concentrations (range, 174 to 588 mg/dl) that were always greater than concurrent serum values. Diagnosis was delayed 3.0 +/- 1.5 days (range, 0 to 11 days) after vascular erosion. One patient died and four patients received chest tubes. Seven of eight patients had left-sided line placement; six of these seven left-sided catheters abutted the superior vena cava wall within approximately 45 degrees of perpendicular. Results of a literature search confirm the hazards of delayed diagnosis and the importance of left-sided catheter placement as a risk factor for vascular erosion. PMID- 1600786 TI - Effects of doxapram on hypercapnic response during weaning from mechanical ventilation in COPD patients. AB - Failure of weaning from mechanical ventilation in COPD patients is often related to diaphragmatic fatigue. Whether there is a central respiratory drive fatigue and a reserve of excitability is still debated. The purpose of this study was to analyze the following in 13 COPD patients weaned from mechanical ventilation: (1) ventilatory (VE/PETCO2) and neuromuscular (P0.1/PETCO2) response to hypercapnia; (2) the maximum reserve capacity measured through changes in the VE/PETCO2 and P0.1/PETCO2 slopes after doxapram (DXP) infusion, which, given during the test, allows measurement of the maximum response capacity to overstimulation; and (3) analyze the influence of these changes on the outcome of weaning. The results show a variable P0.1/PETCO2 response and a low VE/PETCO2. DXP infusion does not change the slopes of these relations but increases the end-expiratory volume (delta FRCd); (p less than 0.02). Since there was no change in the VE/PETCO2, P0.1/PETCO2, and delta FRC values with or without DXP, there was no excitability reserve in patients who were successfully weaned. When weaning failed, DXP did not change VE/PETCO2 and P0.1/PETCO2 slope, but delta FRCd was greater the delta FRC (p less than 0.001). The excitability reserve in these patients leads to an increase in end-expiratory volume, probably worsening the diaphragm dysfunction. PMID- 1600787 TI - Evaluation of definitions for sepsis. AB - OBJECTIVE: To evaluate the current definitions for sepsis and clarify and quantify the risk for intensive care unit (ICU) patients with sepsis. DESIGN: A prospective cohort analysis of 519 patients with a primary clinical diagnosis of sepsis treated in the ICUs of 40 US hospitals drawn from a nationally representative sample of 17,440 admissions. MEASUREMENTS: Patient's age, treatment location prior to ICU admission, comorbidities, origin of sepsis, daily physiologic measurements, therapeutic intensity, and subsequent hospital mortality rate. INTERVENTION: Patients were categorized into subgroups by important risk factors and into current clinical definitions of sepsis. Patients also were provided an individual risk of hospital mortality based on their individual predicted risk by using the first ICU day APACHE III score, treatment location prior to ICU admission, and etiology of sepsis. RESULTS: Patients with a designated urinary source of sepsis had a significantly lower baseline risk of death (30 percent) than patients with other causes (54 percent, p less than 0.01). Patients admitted to the ICU from the emergency department also had significantly lower mortality (37 percent) than patients admitted from hospital wards, other units within the hospital, or transferred from other hospitals (55 percent, p less than 0.01). Recognized definitions such as "sepsis syndrome" and "septic shock" identified groups of patients with significantly different mortality rates, 40 percent and 64 percent, respectively (p less than 0.01), but the range of individual patient risks within these groups were indistinguishable from the 211 patients (41 percent) that did not meet these definitions during the initial seven days of ICU treatment. Multivariate analysis using initial APACHE III score, etiology (urosepsis or other), and treatment location prior to ICU admission provided the greatest degree of discrimination (ROC = 0.82) of patients by risk of hospital death. CONCLUSIONS: Sepsis is a complex clinical entity and could be viewed as a continuum with substantial variation in initial severity and risk of hospital death. One accurate description of sepsis is the continuous measure of hospital mortality risk estimated primarily from physiologic abnormalities. PMID- 1600788 TI - Body plethysmography in the evaluation of intrathoracic airway abnormalities. AB - A patient with a previously unsuspected intrathoracic tracheal malignancy presented with symptoms suggestive of asthma and an unusual pattern seen by conventional PFTs. Reduced expiratory flows with a large difference between FVC and SVC, normal inspiratory flows and high MVV/FEV1 were found. Body plethysmography using normal and panting efforts with increasing tidal volume and flow helped define the lesion as a variable intrathoracic obstruction and document its regression after palliative therapy. PMID- 1600789 TI - Active intrathoracic tuberculosis with clear lung fields. PMID- 1600790 TI - Multiple pulmonary nodules with cavitation and fever in a 48-year-old man. PMID- 1600791 TI - Capnometry during high-frequency oscillatory ventilation. AB - We used capnometry during high-frequency oscillatory ventilation (HFOV), and compared CO2 measurements at the distal and proximal ends of an endotracheal tube with arterial CO2 values. Ten white rabbits (mean weight, 2.00 +/- 0.2 [SD] kg) underwent tracheostomy under anesthesia with pentobarbital. The trachea was intubated with an endotracheal tube with a second lumen for sampling respiratory gas at the distal tip. Capnometry was performed through the lumen (CO2d) and the proximal end of the endotracheal tube (CO2p). The internal carotid artery was cannulated to sample blood for measuring arterial blood gases. The differences between CO2d, CO2p, and PaCO2 were measured. Only the relation between CO2d and PaCO2 was good (r = 0.915). We concluded that capnometry can be used during HFOV to estimate PaCO2 provided that respiratory gas is sampled from the distal tip of the endotracheal tube. PMID- 1600792 TI - Coronary thrombolysis. Comparative effects of intracoronary administration of recombinant tissue plasminogen activator and urokinase. AB - We employed a canine model of coronary thrombosis, induced by injection of radioactive blood clot, via a catheter placed in the left anterior descending coronary artery, to compare effects of intracoronary administration of recombinant tissue plasminogen activator (rtPA) and urokinase (UK) on rate and extent of coronary thrombolysis. Two doses of UK, 15,000 U/kg (UK15) and 30,000 U/kg (UK30) and two doses of rtPA, 0.25 mg/kg (rtPA.25) and 0.75 mg/kg (rtPA.75) were given. Drugs were infused over 45 min. Compared with the other regimens, rate and extent of coronary thrombolysis were significantly increased with rtPA.75. Also, despite a much higher dose of UK, coronary thrombolysis was similar with UK30 and rtPA.25. Compared with UK15, rate and extent of coronary thrombolysis were increased with rtPA.25. These results indicate that intracoronary administration of rtPA is superior to intracoronary UK in inducing thrombolysis. PMID- 1600793 TI - Prevalence of high hematocrits in patients with interstitial lung disease in Mexico City. AB - Erythrocytosis, a known response to chronic hypoxemia, is considered infrequent in interstitial lung diseases. We studied the prevalence of high hematocrit (Hct) values and the relationship between Hct and SaO2 in 79 patients with chronic pigeon breeder's lung (PBL) and 34 with idiopathic pulmonary fibrosis (IPF), all of whom lived in the Mexico City metropolitan area (2,240 m above sea level). Lung biopsy was performed in 31 patients with IPF and 71 with PBL. We analyzed only one simultaneous measurement of Hct and SaO2 per patient (usually the initial measurement) before treatment. No additional cause for anemia or erythrocytosis was detected. Forty-eight percent of the patients with PBL (38/79) and 62 percent of those with IPF (21/34) had high Hct values (greater than 2 SD above mean values for Mexico City); in 14 (12.3 percent) of the 113 patients (nine with PBL and five with IPF), the Hct was above 60 percent. The Hct and SaO2 values displayed a poor correlation for the whole group: Hct = 65.7-0.16(SaO2), r = 0.24, p = 0.012. The correlation between Hct and SaO2 was nonsignificant if patients were separated by diagnosis. For an SaO2 of less than 80 percent, the slope of SaO2 vs Hct was zero. Half of our patients with PBL and IPF had Hct values that were high for the altitude. In most cases, Hct responses fell within the confidence limits reported as normal at high altitudes. We found a poor relationship between Hct and awake SaO2. PMID- 1600794 TI - Discordance between cardiopulmonary physiology and physical therapy. Toward a rational basis for practice. PMID- 1600795 TI - Mitral stenosis in pseudoxanthoma elasticum. AB - A 54-year-old woman with pseudoxanthoma elasticum presented with tight mitral stenosis with thickened and restricted mitral valve leaflets. She initially revealed systemic hypertension and moderate mitral regurgitation due to mitral valve prolapse. One year after the start of treatment for hypertension, thickening of the mitral valve gradually progressed and she showed tight mitral stenosis without regurgitation. It was considered that another differential diagnosis must be added to the uncommon causes of mitral stenosis. PMID- 1600796 TI - Pulmonary eosinophilia in pulmonary tuberculosis. AB - Three radiologically and bacteriologically confirmed pulmonary tuberculosis patients had eosinophilic pneumonia, as demonstrated by BAL. In two patients, pulmonary eosinophilia was present only at the site of the lesion and the third had eosinophilia in both peripheral blood and lung. There was complete elimination of the eosinophilic inflammatory process in two patients who had successfully completed antituberculosis treatment. PMID- 1600797 TI - Parapneumonic empyema. A pitfall in diagnosis. AB - Two patients eventually shown to have empyema were encountered in which the initial thoracentesis revealed fluid compatible with either a simple or a complicated parapneumonic effusion. In both cases, the diagnosis of empyema was made by a second thoracentesis done at a close interval of time from a different site. Therefore, the physician should approach parapneumonic effusions systematically, and remember that in some cases, multiple thoracenteses may be required to make the correct diagnosis of an empyema. PMID- 1600798 TI - Adult T-cell leukemia/lymphoma presenting as an acute noninfectious pneumonitis. AB - A 29-year-old man presented with a four-week history of pneumonic symptoms and progressive roentenographic infiltrates which were unresponsive to orally administered antibiotics. Bronchoscopy failed to identify an infectious etiology, but abundant atypical lymphocytes in the bronchial washings were present. A diagnosis of adult T-cell leukemia/lymphoma was subsequently made. After administration of cancer chemotherapy, the pneumonic symptoms and chest roentgenogram infiltrates resolved. This report suggests that ATL can present as an acute noninfectious pneumonitis. PMID- 1600799 TI - Respiratory syncytial virus infection in an adult with Wegener's granulomatosis. AB - Respiratory syncytial virus (RSV) has been documented as a pathogen in adults who are immunocompromised because of various underlying conditions. To our knowledge, this is the first report of a patient with Wegener's granulomatosis (WG) and RSV infection resulting in a fatal outcome. PMID- 1600800 TI - Hemianomalous pulmonary venous connection of the left lung surgically corrected. AB - Hemianomalous pulmonary venous connection is a rare congenital abnormality that leads to significant left-to-right shunt and complications related to that. Earlier surgical correction of this disorder was associated with the problem of stenosis at the anastomotic site with the left atrium. We describe the diagnosis of this abnormality in a 24-year-old woman and present the details of surgery to avoid the stenosis at the site of anastomosis. PMID- 1600801 TI - Occupational asthma in a beet sugar processing plant. AB - A patient with occupational asthma in the beet sugar processing industry is described. Symptomatology, skin testing, immunologic testing, and specific bronchoprovocation testing indicate exposure to moldy sugar beet pulp was the cause of the patient's occupational asthma. Cooperation between the treating physician and public health authorities is encouraged. PMID- 1600802 TI - Direct extension of bronchogenic carcinoma through pulmonary veins into the left atrium mimicking left atrial myxoma. AB - Direct extention of bronchogenic carcinoma via pulmonary veins into the left atrium is rare. We describe two such cases, one which presented as a left atrial mass with pulmonary edema, and another which was detected at autopsy. PMID- 1600803 TI - Fatal hyperthermia in a quadriplegic man. Possible evidence for a peripheral action of haloperidol in neuroleptic malignant syndrome. AB - A patient with a cervical cord transection isolating his hypothalamic thermoregulatory centers from peripheral effectors suffered a fatal hyperthermic episode after receiving haloperidol. This suggests that neuroleptic malignant syndrome is caused by a peripheral, not central, effect of haloperidol. PMID- 1600804 TI - Acute myocardial infarction associated with intravenous injection of pentazocine and tripelennamine. AB - This case report describes the evolution of an acute anteroseptal myocardial infarction in a 27-year-old man following intravenous injection of pentazocine and tripelennamine. Subsequent coronary angiography showed normal coronary arteries. Based on the known mechanism of action of these drugs, it is postulated that myocardial infarction resulted from coronary artery spasm secondary to excessive catecholamine stimulation. PMID- 1600805 TI - Mitral and tricuspid annular endocarditis. Diagnosis by transesophageal echocardiography. AB - Two cases of infective endocarditis with vegetations attached to the mitral and tricuspid annuli are described. In both cases, the vegetations could not be identified by transthoracic echocardiography. These cases illustrate the advantage of TEE over the transthoracic approach in recognizing vegetations in extravalvular locations. PMID- 1600806 TI - The clinical manifestations of cardiac mucormycosis. AB - The manifestations of cardiac mucormycosis may dominate the clinical picture of disseminated mucormycosis. These manifestations include myocardial infarction, congestive heart failure, conduction system disease, valvular imcompetence and pericarditis. The development of such manifestations in a febrile compromised host with one or more predisposing factors should prompt consideration of disseminated mucormycosis in the differential diagnosis and initiation of appropriate diagnostic and therapeutic strategies. PMID- 1600807 TI - Chylothorax due to benign lymphangioma. PMID- 1600808 TI - Treatment of bronchopleural fistulas. PMID- 1600809 TI - Endobronchial streptokinase for relief of tracheobronchial obstruction by blood clots. PMID- 1600810 TI - Right-sided aortic arch. PMID- 1600811 TI - Airway obstruction by a mucus ball from a transtracheal oxygen catheter. PMID- 1600812 TI - Airway obstruction by a mucus ball from a transtracheal oxygen catheter. PMID- 1600813 TI - Drug treatment of chronic tuberculous empyema. PMID- 1600814 TI - Inflammatory pseudotumor arising from the hilum and invading the subepithelium. PMID- 1600815 TI - Spontaneous pneumomediastinum. PMID- 1600816 TI - Spontaneous pneumomediastinum. PMID- 1600817 TI - Acute asthma. Utility of admission chest radiography. PMID- 1600818 TI - Chronic mountain sickness. PMID- 1600819 TI - A comparative study of black South African children from three different contexts. AB - This study compares family characteristics and developmental outcomes of black children (N = 300) from 3 rural contexts in South Africa: the homeland, the resettlement, and the white-owned farms. Parents in the homeland were more likely to be married and had more education, less household crowding, and lower mobility than parents in the other 2 areas, and higher occupational status than parents from the farms. Child outcomes paralleled these differences in material resources and family stability. Children from the homeland scored higher than children from the resettlement or farms on head circumference, vocabulary, quantitative skill, and self-concept, with no significant differences between the latter 2 areas on these outcome variables. Children from the homeland also scored higher than resettlement children on weight, copying skill, and height, with children from the farms measuring lowest on height. Child outcomes were highly intercorrelated in all 3 residence areas, but correlations among family variables, and between family and child variables, showed different patterns across areas. Parent education, occupation, and crowding were the most consistent predictors of physical development, cognitive development, and self-concept. Family mobility and marital status, however, showed different relationships to other family variables and to child outcomes across the 3 environments. These results highlight the importance of studying children in multiple environmental contexts, because family characteristics are not associated uniformly across residence areas. PMID- 1600820 TI - A family process model of economic hardship and adjustment of early adolescent boys. AB - We propose a family process model that links economic stress in family life to prosocial and problematic adolescent adjustment. Employing a sample of 205 seventh-grade boys aged 12 to 14 years (M = 12.7) and living in intact families in the rural Midwest, the theoretical constructs in the model were measured using both trained observer and family member reports. In general, results were consistent with the proposed model. Objective economic conditions such as per capita income and unstable work were related to parents' emotional status and behaviors through their perceptions of increased economic pressures such as the inability to pay monthly bills. These pressures were associated with depression and demoralization for both parents, which was related to marital conflict and disruptions in skillful parenting. Disrupted parenting mediated the relations between the earlier steps in the stress process and adolescent adjustment. The emotions and behaviors of both mothers and fathers were almost equally affected by financial difficulties, and disruptions in each parent's child-rearing behaviors had adverse consequences for adolescent development. PMID- 1600821 TI - A prospective study of life stress, social support, and adaptation in early adolescence. AB - This study employed a 2-year longitudinal design to examine the relation of stressful life events and social supports to psychological distress and school performance among 166 early adolescents (mean age = 13.5 years). A prospective approach was utilized to control for initial levels of adjustment when examining the relation of Time 1 stress and support variables to Time 2 psychological distress and school performance. Both stress and support variables made significant contributions to the prediction of subsequent psychological distress. Stresses, but not supports, made a significant contribution to the prediction of subsequent school performance. Evidence for reciprocal and interactive linkages was also found, including effects of psychological distress and school performance on subsequent stresses and supports, and greater adaptive impact of school-based supportive resources under conditions of heightened risk outside of school. Implications for ecological and transactional models of development relating to the targeting and efficacy of preventive efforts are discussed. PMID- 1600822 TI - Assessing marital conflict from the child's perspective: the children's perception of interparental conflict scale. AB - Guided by Grych and Fincham's theoretical framework for investigating the relation between interparental conflict and child adjustment, a questionnaire was developed to assess children's views of several aspects of marital conflict. The Children's Perception of Interparental Conflict Scale (CPIC) was initially examined in a sample of 222 9-12-year-old children, and results were cross validated in a second sample of 144 similarly aged children. 3 factor analytically derived subscales (Conflict Properties, Threat, Self-Blame) demonstrated acceptable levels of internal consistency and test-retest reliability. The validity of the Conflict Properties scale was supported by significant relations with parent reports of conflict and indices of child adjustment; the Threat and Self-Blame scales correlated with children's responses to specific conflict vignettes. The CPIC thus appears to be a promising instrument for assessing perceived marital conflict, and several issues regarding its interpretation are discussed. PMID- 1600823 TI - Determinants of disciplinary practices in low-income black mothers. AB - Disciplinary attitudes and practices of low-income black mothers were examined. Mothers were interviewed about their parenting attitudes and control practices, and their responses were coded in terms of the degree to which they took a parent versus a child-oriented approach to discipline. Mothers in the sample varied widely in their attitudes toward physical punishment, and mothers who used power assertive techniques were as likely to take the child's perspective and give input into the socialization process as those who did not. Factors associated with maternal disciplinary styles included: maternal education, father absence, maternal age, and self-reported religious beliefs. Findings are discussed in terms of the variability in disciplinary practices in this population, as well as the factors contributing to these individual differences. PMID- 1600824 TI - The relations of maternal practices and characteristics to children's vicarious emotional responsiveness. AB - This study examined the relations of maternal vicarious emotional responding and child-rearing practices, as well as familial emotional environment, to 5-6 and 8 9-year-old children's vicarious emotional responding. There were some correspondences between mothers' and children's heart rate, facial, and self reported reactions to a sympathy-inducing film. Maternal sympathy/perspective taking and reinforcement of sympathy/prosocial behavior, as well as negative subordinate emotion in the home, were associated with markers of girls' sympathy; mothers' personal distress (for girls), restrictiveness regarding displays of hurtful negative emotions (particularly for young girls), and negative dominant emotion in the home (for both sexes) were associated with markers of personal distress. Mothers' linking of the film character's experience to children's own experience was associated with children's responsiveness to the film, and mother's verbalizations during the film concerning her own emotional state and role taking were associated with boys' self-reported sympathy. PMID- 1600825 TI - Family-peer connections: the roles of emotional expressiveness within the family and children's understanding of emotions. AB - The purpose of this study was to explore patterns of parent and child emotional expressiveness within the family context, to examine links between these patterns and children's peer relations, and to examine whether these links might be mediated by children's understanding of emotions. Subjects were 61 kindergarten and first-grade white, middle-class children and their parents. Parent and child expressiveness were assessed in a laboratory ring-toss game designed to elicit a range of emotional responses. Parent expressiveness in the home was also assessed with Halberstadt's Family Expressiveness Questionnaire. The questionnaire, completed by both mother and father, assesses a range of emotions in a variety of settings typical of many families, and consists of items tapping both positive and negative expressiveness. Children were interviewed about their understanding of emotions across a broad range of areas. Results indicated that maternal expressiveness (home) and paternal expressiveness (home and laboratory) but not children's expressiveness with parents were associated with children's peer relations. Although children's understanding of emotions was generally not associated with family expressiveness, understanding predicted children's peer relations. In addition, children's understanding influenced the links between maternal expressiveness in the home and peer relations and between paternal expressiveness in the laboratory and peer relations. This pattern of results underscores the importance of the emotional climate of the family for the development of children's social relations with peers. PMID- 1600826 TI - Self-evaluations and intergroup attitudes in children aged three to nine. AB - The effects of individual and group performance on children's evaluations of themselves and in- and out-group were examined. 128 girls and boys aged 3, 5, 7, and 9 years were randomly assigned to alleged "fast" or "slow" teams and asked to make various self, interpersonal, and intergroup evaluations. These showed strong developmental changes. Intergroup comparisons were made as early as 3 years, and this age group was sensitive to the relative standing of their team. However, the 5-year-old children showed markedly high self-evaluations, very strong in group bias in their evaluations of the 2 teams, and a high level of group cohesion irrespective of their own team's alleged performance. Gender differences were observed in self-evaluations after team assignment (boys responding more than girls to their team's alleged performance). The implications of these findings for recent work based on cognitive-developmental and social identity theories are discussed. PMID- 1600827 TI - Differences in shame and pride as a function of children's gender and task difficulty. AB - 3-year-old children were presented with easy and difficult tasks and their emotional responses of shame and pride were observed. No shame was shown when subjects succeeded on the tasks and no pride was shown when they failed. Significantly more shame was shown when subjects failed easy tasks than when they failed difficult tasks, and significantly more pride was shown when subjects succeeded on difficult than on easy tasks. While there were no sex differences in task failures, girls showed more shame than boys. There were no sex differences in pride when subjects succeeded. PMID- 1600828 TI - Children's interpretation of messages from a speaker with a false belief. AB - In 5 investigations we examined a new procedure for assessing children's understanding that messages arise from speakers' internal representations. 3- and 4-year-olds watched the enactment of a message-desire discrepant story in which a speaker doll, who believed wrongly that bag A was in location 1 and that bag B was in location 2, gave a message referring to the bag in location 1. In a message-desire consistent control condition, the speaker had a correct belief about the bags' locations. Children frequently judged correctly in the discrepant story that the speaker (who specified location 1) wanted the bag in location 2, and judged correctly in the consistent story that the speaker wanted the bag in location 1. That is, young children attended to the speaker's internal representations, and not just the real-world referent of the message, when judging what the speaker wanted. In one of the investigations, children performed better on the message-desire discrepant task than on a false belief task. We discuss why they might find it particularly easy to take into account false belief when inferring desire on the basis of behavior. PMID- 1600829 TI - The teacher's role in facilitating memory and study strategy development in the elementary school classroom. AB - The efforts of 69 elementary school teachers to instruct children in cognitive processing activities were observed. Although the teaching of such activities was relatively infrequent, it varied by grade (occurring more often in grades 2-3 than in higher or lower grades) and by the content of instruction. Teachers of grade 4 and above more often provided rationales for the use of cognitive strategies than did teachers of younger children. In a second study, children of three achievement levels were selected from classrooms in which teachers varied in their use of suggestions regarding cognitive processes. Subsequent to training in the use of a memory strategy, children's performance on a maintenance trial was evaluated: Among average and low achievers, those whose teachers were relatively high in strategy suggestions showed better maintenance and more deliberate use of the trained strategy than did children whose teachers rarely made strategy suggestions. The role of school experience in the development of children's memory skills is discussed. PMID- 1600830 TI - Knowledge, concepts, and inferences in childhood. AB - The role of knowledge in children's inferences was investigated in 3 experiments. Experiment 1 examined developmental changes in the role of categorical membership, perceptual appearance, and item complexity in inferences for natural kind and artifact concepts. Preschoolers (5-year-olds), second graders (8-year olds), and fourth graders (10-year-olds) were taught novel properties about target concepts and asked whether each of 4 probes had those properties. Probes varied in category membership and perceptual appearance relative to the target item. Item complexity also varied. Experiments 2 and 3 examined inferences with known and unknown concepts for familiar and unfamiliar properties. Older children's knowledge led to differential weighting of categorical information over appearance but only for known concepts and/or familiar properties. Preschoolers made no distinction between category and appearance for either known or unknown concepts. Additionally, as target item complexity increased, older children made more inferences than preschoolers. No differences between inferences about natural kind and artifact concepts were found. The role of theories and knowledge in children's drawing of inferences is discussed. PMID- 1600832 TI - Frontal lobe activity and affective behavior of infants of mothers with depressive symptoms. AB - Studies of adults and infants indicate that the left frontal brain region is specialized for approach emotions, such as joy, whereas the right frontal region is specialized for withdrawal emotions, such as distress. Furthermore, depressed adults have been found to show reduced brain activity in the left frontal region. In this study, frontal and parietal electroencephalographic (EEG) activity was recorded from 27 infants aged 11-17 months (13 of whose mothers reported elevated depressive symptoms) during baseline and emotion-eliciting conditions. Compared with infants of nonsymptomatic mothers, infants of symptomatic mothers exhibited reduced left frontal brain activity during playful interactions with their mothers and failed to exhibit the typical pattern of greater right frontal activity during a condition designed to elicit distress (maternal separation). Infants of symptomatic mothers also showed less distress during maternal separation; however, no group differences in behavior were found during the playful condition. Group differences were evident in the frontal region, but not in parietal brain activity. PMID- 1600831 TI - Visual expectation and dimensions of infant information processing. AB - Visual expectation was assessed in 103 black 6.5-month-olds using Haith, Hazan, and Goodman's paradigm and related to performance on standard developmental assessments and tests of information processing skill. As expected, percent anticipations was higher and RT lower than in 3.0-month-olds previously tested. Split-half and left-right correlations for the RT measures were moderate and similar to those previously reported, as was split-half reliability for percent anticipations. The 2 RT measures were related to fixation duration on both visual recognition memory (VRM) and cross-modal transfer, suggesting moderate cross-task and cross-age consistency in processing speed. Percent anticipations and baseline RT each contributed independently to the prediction of VRM novelty preference. Data from a factor analysis suggested 3 dimensions of cognitive function: processing speed, developmental level, and memory/attention. These findings suggest that the visual expectation paradigm provides a reliable new approach for assessing cognitive processing efficiency and attention during infancy. PMID- 1600833 TI - The relation between attachment and knowledge of self and mother in one to three year-old infants. AB - The relation between attachment to mother and knowledge of self and mother in 2 domains was assessed in 1- to 3-year-old infants. Infants' featural knowledge was measured by featural recognition, name, possession, and gender. In this domain, no difference between the 2 attachment classifications was obtained at 1 year of age, but significant and increasingly large differences between securely and insecurely attached infants were found at 2 and 3 years of age. The second domain measured infants' actions on self and mother in the context of symbolic play. Regardless of age, infants who were securely attached to mother acted on self and mother with greater complexity than did infants who were insecurely attached. Attachment was related equally to the complexity of infants' knowledge of self and mother. These data were discussed in the context of the development of infants' internal working models of attachment and the onset of representational ability. PMID- 1600834 TI - Sulfonylureas in NIDDM. AB - Sulfonylureas have represented the backbone of oral therapy in non-insulin dependent diabetes mellitus for greater than 30 yr. Despite this, our knowledge about the mode of actions of these agents is limited, and the use of them is far from rational. Sulfonylureas lower blood glucose concentrations primarily by stimulating insulin secretion. The evidence for clinically significant extrapancreatic effects is scanty. Therefore, the effect of sulfonylurea is limited to patients with preserved beta-cell function, with the best effect observed in the early stages of the disease. Sulfonylurea treatment is often started relatively late and is continued when the agents can no longer achieve the treatment goals. Drug dosages are increased to maximum recommended doses, although there is no evidence for a dose-response relationship between the sulfonylurea dose and its biological effect. To rationalize the use of sulfonylureas, we should ask the questions to whom, how much, and for how long? The decision to stop treatment is as important as the decision to start treatment. PMID- 1600835 TI - Biguanides and NIDDM. AB - The main biguanides, metformin and phenformin, were introduced in 1957 as oral glucose-lowering agents to treat non-insulin-dependent diabetes mellitus (NIDDM). Phenformin was withdrawn in many countries because of an association with lactic acidosis, but metformin does not have the same risk if appropriately prescribed. Metformin is now widely used as a monotherapy and in combination with a sulfonylurea. Unlike sulfonylureas, metformin is not bound to plasma proteins, is not metabolized, and is eliminated rapidly by the kidney. The glucose-lowering effect occurs without stimulation of insulin secretion and results mainly from increased glucose utilization. The presence of insulin is required, and enhancement of insulin action at the postreceptor level occurs in peripheral tissues such as muscle. In peripheral tissues metformin increases insulin mediated glucose uptake and oxidative metabolism. Metformin also increases glucose utilization by the intestine, primarily via nonoxidative metabolism. The extra lactate produced is largely extracted by the liver and serves as a substrate to sustain gluconeogenesis. This limits the extent to which metformin reduces hepatic glucose production but provides a safeguard against excessive glucose lowering. Because metformin does not cause clinical hypoglycemia, it is actually an antihyperglycemic drug. It does not cause weight gain, it helps combat hypertriglyceridemia, and it has been ascribed some vasoprotective properties. Metformin offers a useful treatment for insulin-resistant overweight NIDDM patients. PMID- 1600836 TI - Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus. AB - There are elevated fatty acid levels in non-insulin-dependent diabetes mellitus that are due to diminished insulin action in inhibiting fatty acid release from adipocytes. Insulin therapy and other inhibitors of fatty acid release from adipocytes (e.g., nicotinic acid) suppress these elevated fatty acid levels and bring about a reduction in hyperglycemia. One mechanism by which fatty acids may be causal in hyperglycemia is in stimulating gluconeogenesis in the liver in the postabsorptive state. Another mechanism is in attenuating glucose disposal in skeletal muscle in the fed state. Potential nonglycemia-related effects of fatty acids are in substrate utilization in the heart and lipid synthesis in the liver. Inhibition of fatty acid oxidation is useful in reducing hyperglycemia by inhibiting glucose production in humans. However, there is less evidence that such inhibition can be useful in increasing glucose utilization in muscle, as predicted by the Randle hypothesis. This, coupled with potential adverse effects on heart muscle, make liver targeting of fatty acid oxidation inhibitors an important factor in their potential for development. Although such agents have advantageous effects on lipid metabolism, overdosing can lead to adverse liver lipid effects via the same mechanism. These adverse liver lipid effects could be minimized by development of reversible inhibitors that allow fatty acid oxidation to occur only during the overnight fast. The potential usefulness of such agents is evident; however, no drug that meets these objectives has been developed. PMID- 1600837 TI - Dichloroacetate. AB - Dichloroacetate (DCA) represents a potentially novel class of oral antidiabetic agents that reduce blood glucose and lipids without stimulating insulin secretion. DCA reduces blood glucose by inhibiting hepatic glucose synthesis and stimulating glucose clearance and use by peripheral tissues. A major site of action of the drug is pyruvate dehydrogenase (PDH), the rate-limiting enzyme of aerobic glucose oxidation. Stimulation of PDH by DCA increases peripheral oxidation of alanine and lactate, thereby interrupting the Cori and alanine cycles and reducing the availability of three-carbon precursors for gluconeogenesis. In experimental models of ketosis, DCA reduces ketonemia and ketonuria while significantly lowering blood glucose. DCA inhibits hepatic triglyceride and cholesterol biosynthesis. Short-term studies in patients with non-insulin-dependent diabetes have demonstrated a capacity of the drug to markedly reduce circulating a very-low-density lipoprotein cholesterol and triglyceride concentrations. In genetic models of insulin-dependent diabetes, oral administration of DCA significantly reduces insulin requirements and blood levels of glucose and triglycerides. Several derivatives of DCA have been synthesized and found to have biological activity in animals. Further work is required to determine whether DCA and its analogues may be safe and effective agents for chronic treatment of the carbohydrate and lipid abnormalities of human diabetes. PMID- 1600838 TI - New pharmacological approaches to therapy of NIDDM. AB - Currently available pharmacological agents have not been completely successful in restoring euglycemia in the non-insulin-dependent diabetes mellitus (NIDDM) patient. Several new approaches to the therapy of NIDDM have been formulated in recent years and are in various stages of laboratory or pharmaceutical development. Several of these agents are discussed in this article under categories relating to their mechanisms of lowering blood glucose: 1) inhibition of the release or action of counterregulatory hormones; 2) inhibition of postprandial glucose rise; 3) sensitization of tissues to insulin's actions; and 4) inhibition of gluconeogenesis, including inhibition of the long-chain acyl-CoA carnitine acyltransferase I, the long-chain acylcarnitine translocase, and pyruvate carboxylase. PMID- 1600839 TI - Diplophthalmia versus cyclopia and synophthalmia. Mechanisms of doubling of the eye. AB - In historical and many scientific papers of the 20th century double formation of eyes has been described as cyclopia, which develops as a variably marked fusion of both eye anlagen into a single eye in median position. In contrast with mythology, no cases were viable, as cyclopia is always accompanied by other severe deformities, such as cerebral defects and proboscis. For the first time a double eye on one side - a unilateral diplophthalmia - in a viable child born in Austria is presented after a reviewal of fundamentals of general and experimental embryology, cyclopia and unilateral synophthalmia. Unlike cases of cyclopia with two fused eyes from two anlagen in one single orbit, we found a total of three eyes from two anlagen in two orbits; a normally developed eye in the right orbit and a double eye in the left with no proboscis. In addition porencephaly, a double canine tooth, and a lateral branchial cyst were also present on the left side. An examination of this unique case partially corroberated the findings of experimental embryology as to the normal formation of the lens and brought to light new findings concerning the formation of the vitreous body and the retina, because in the 'extra' left eye a hyaloid artery did not develop. There was only one optic nerve with a normal optic disc as a guiding structure for this artery in the 'normal' left eye. PMID- 1600841 TI - Effects of laser-induced retinal lesions on perimetric thresholds. AB - Differential light sensitivity and high-pass resolution thresholds were studied before and after pan-retinal photocoagulation in subjects with proliferative diabetic retinopathy. The photocoagulated retinal area was measured and the relative change in ganglion cell separation was estimated. The change in differential light thresholds after treatment, when expressed in decibels, appeared to be linearly related to the calculated change in ganglion cell separation. At present, this empirical finding lacks a theoretical explanation. For high-pass resolution, theory predicts a direct proportionality between the change in ganglion cell separation and resolution threshold. This relationship was confirmed, supporting the claim that high-pass resolution directly reflects the number of functional retino-cortical neural channels. PMID- 1600840 TI - Induction of vascular haemostasis by Nd:YAG laser light in melanin-rich and melanin-free tissue. AB - Haemostasis was effected in vessels of melanin-rich (MR: choroid) and melanin free (MF: mesentery) rabbit tissue irradiated with a cw-Nd:YAG laser. The following parameters were employed: - pulse duration: 200 ms (MR) and 100 ms (MF); focal spot diameter: 200 microns (MR) and 80 microns (MF); pulse energies: 100-250 mJ (MR) and 0.5-1 J (MF); irradiances: 1.6-4.0 kW cm-2 (MR) and 1-2 x 10(2) kW cm-2 (MF). In melanin-rich tissue, laser energy is absorbed principally by melanin granules contained within the stromal melanocytes. The heat generated in these structures radiates into the surrounding tissue where it is dissipated. The damage thus incurred by the endothelium of blood vessels encompassed within this field triggers the haemostatic mechanism whereby blood flow is arrested. This effect is realized by the formation of an occluding plug of platelets, which is stabilized by the deposition of fibrin, particularly in capillaries, and to a lesser degree in larger vessels of the vascular lamina. In melanin-free tissue, haemoglobin serves as the primary site of energy absorption, which is thus shifted from the stroma to the vessel lumen. Irradiation of vessels in such tissue leads to thermocoagulation of plasma proteins and consequent stasis of blood flow. PMID- 1600842 TI - Does work with visual display units impair visual activities after work? AB - It is well established that visual display unit (VDU) operators complain of visual fatigue and visual stress during after-work hours. The present study was divided into two parts. In the first part, standard eye examinations were performed on a group of VDU workers (n = 32) and a control group (n = 15); those subjects who were found to have correct vision (n = 16 and 13, respectively) participated in the second part. The eye examinations revealed that on the average, the VDU workers suffered more than twice as many visual impairments as the controls. In those with correct vision, the near point of accommodation was measured at the beginning of the workday at the start of the week, and at the end of the workday, four days later. In the VDU group, the decrease in accommodation was uniformally distributed between zero and 1.0 diopter, whereas among the non VDU workers, 77% of the decrease was between zero and 0.25 diopter. The dynamic range of accommodation in the VDU workers on the second examination was smaller than on the first. We conclude that some of the visual stress and visual fatigue that developed at work hindered visual activities after work. PMID- 1600843 TI - Effects of repeated ivermectin treatment in onchocerciasis. AB - A group of 87 onchocerciasis patients from a hyperendemic area without vector control was treated with a single dose of 150 micrograms/kg ivermectin. A second, third and fourth dose was administered 5, 12 and 17 months later to 44, 35 and 25 patients. Skin snip loads reduced substantially following each consecutive dose. However, after three doses 44% of the patients remained skin snip positive. Side effects decreased from 32.2% requiring medical treatment at the first dose to none after the fourth dose. From this study it was concluded that a complete eradication of microfilariae in skin snips in severely infected persons living in a hyperendemic area without vector control is probably not feasible. Medical supervision for the observation of side-effects after the third dose can be limited. PMID- 1600844 TI - Fungal keratitis in Saudi Arabia. AB - We studied a total of 27 cases of fungal keratitis is Saudi Arabia. History of trauma was found in 9 patients, and previous use of topical steroids in 6 patients. In the majority of patients the onset of the disease was in fall and spring. The most frequent cause of fungal keratitis was found to be Aspergillus spp., and these were isolated from 11 cases (41%). Eight of the 11 isolates were Aspergillus flavus. Other causes of keratomycosis included: Fusarium, Candida, and Mycelia sterilia. All patients were treated with antifungal therapy and 18 patients required surgical intervention. Vision improved among 11 patients, remained the same in 4 patients, and deteriorated after treatment in 6 patients. (6 patients failed to return for follow-up.) Four of the 27 patients developed fungal endophthalmitis. The high prevalence of Aspergillus spp. may be due to the fact that spores of Aspergillus can survive the hot and dry weather of Saudi Arabia. PMID- 1600845 TI - Ocular surface lesions due to keratoconjunctivitis sicca: in primary Sjogren's syndrome. AB - Keratoconjunctivitis sicca is usually part of Sjogren's syndrome (SS) which is systemic disease. Ocular surface lesions are ascribed either to the reduction, or to to the low quality of tears. To address this question, ocular surface lesions were evaluated in 20 SS patients by the rose bengal test (RBT). The results were compared to those obtained in 20 normal volunteers and collated with the quality (estimated by the break-up-time) and the quantity of tears (estimated by the shirmer's I test and the level of lacrimal lactoferrin, LF). The RBT scores did not correlate with the shirmer's test results, neither did they with the break-up times. This is consistent with the view that Schirmer's I Test and break-up-time cannot make any distinction between patients from controls. In contrast, the RBT scores correlated well with the levels lacrimal LF and paralleled to serological abnormalities. PMID- 1600846 TI - Radiation retino- and opticopathy. A prospective study. AB - This is a report of a prospective study of irradiation pathology of retina and optic nerve following radiotherapy for malignant tumors in the region of the nose, pharynx, nasopharynx, and sinuses. The eyes, optic nerves or supplying blood vessels were situated in or near the radiation field. In 16.7% of the cases after an average of 2 1/4 years interval pathology of retina and optic nerve did occur. PMID- 1600847 TI - Alpha-oxidation of fatty acids in fasted or diabetic rats. AB - Induction of alpha-oxidation, a possible gluconeogenic process, which should produce odd-chain fatty acids from even-chain fatty acids, was studied in rats fasted or made diabetic with streptozotocin. When a omega-phenylated even-chain fatty acid, phenylbutyric acid (1.2 mmol/kg), was administered to rats under these conditions, a significant increase in the urinary excretion of benzoic acid, the metabolic end-product of omega-phenylated odd-chain fatty acids, was observed in fasted (3.54 +/- 0.46 mumol/day) and diabetic (6.73 +/- 2.10) rats (control, 0.58 +/- 0.43; P less than 0.001). Phenylated longer chain fatty acids, phenylhexanoic and phenyldecanoic acid, did not produce significantly more benzoic acid than did phenylbutyric acid. Although the rate of alpha-oxidation was very low compared to that of beta-oxidation, these results suggested that alpha-oxidation of fatty acids was induced under fasting or diabetic conditions, and that alpha-oxidation might take place at the butyric acid stage. PMID- 1600848 TI - Partial purification of serum prostacyclin stimulatory activity by heparin agarose column; abnormality detected in diabetics. AB - Human plasma-derived serum (PDS) stimulated the production of 6-keto-PGF1 alpha (a stable metabolite of PGI2) by cultured bovine aortic endothelial cells. The stimulation was both time- and dose-dependent. The main prostacyclin stimulatory activity (PSA) in human PDS remained biologically active after dialysis and was inhibited by the simultaneous addition of heparin. The maximum inhibition of PSA was obtained with 10 micrograms/ml heparin. PDS obtained from patients with non insulin-dependent diabetes mellitus (NIDDM, n = 24) showed significantly less PSA than that from the control subjects (n = 11). A decrease in PSA was also found in diabetic patients using dialyzed PDS. The PSA in human PDS had a specific binding affinity to heparin-agarose and the bound PSA was eluted by a linear gradient of NaCl, which showed two major PSA peaks at 1.0 and 1.5 M NaCl. The dialyzed, mixed PDS from patients with NIDDM and the control subjects was independently applied to a heparin-agarose column and eluted by a linear gradient of NaCl. Comparing the PSA in each peak between the diabetic and the control dialyzed PDS, the PSA at 1.5 M NaCl was markedly decreased in the diabetic patients, but the PSA at 1.0 M NaCl did not change significantly. These observations suggest that the decreased PSA in human diabetic PDS may result mainly from the decrease in the activity of a specific non-dialyzed factor(s) which can bind to heparin. The decreased PSA in serum seems to be responsible in part for decreased PGI2 synthesis by the vascular wall of diabetics. PMID- 1600849 TI - The effect of oral buflomedil on microalbuminuria in non-insulin-dependent diabetic patients. AB - A total of 26 non-insulin-dependent diabetic patients were enrolled for a clinical study of the effect of buflomedil on microalbuminuria. None of the subjects had hypertension or macroproteinuria. Sixteen cases without previously known urinary albumin excretion rate (AER) were enrolled as experimental group. Buflomedil (Loftyl) was administered orally 600 mg daily in two divided doses in the experimental group while AER was determined 3 times with 3 weeks apart in all of the subjects. Ten cases with known microalbuminuria (greater than 8.55 micrograms/min) were enrolled as control group to check the extent of fluctuation in AER from collection to collection in the absence of urinary tract infection. Six of the experimental group showed AER of microalbuminuric level at the time before buflomedil administration and the remaining 10 patients were normoalbuminuric. The effects of buflomedil were compared between the microalbuminuric and normoalbuminuric subjects in the experimental group. The microalbuminuric group showed a significant decrease of AER from a baseline of 30.4 micrograms/min to 19.8 and 16.8 micrograms/min, respectively, after 3 and 6 weeks of treatment (P less than 0.05, Friedman two-way ANOVA). However, the respective values in the normoalbuminuric group were 5.3, 5.6 and 5.0 micrograms/min (P greater than 0.05, Friedman two-way ANOVA). The AER in the control group remained stationary during the study period (14.0, 12.1 and 11.4, respectively, Friedman two-way ANOVA, P greater than 0.05). These results suggest that buflomedil might be beneficial for the patients with microalbuminuria. PMID- 1600850 TI - Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot. AB - We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot. PMID- 1600851 TI - Prevalence of diabetes mellitus in an ambulant elderly New Zealand population. AB - The prevalence of diabetes mellitus (both known and previously undiagnosed) was studied in a population sample, predominantly Caucasoid and resident in the community with an age/sex distribution representative of the New Zealand population aged 65 + years, using WHO criteria. The population sample was randomly selected from the age/sex register of a large urban medical centre in Christchurch, New Zealand. Three hundred and sixty-nine subjects (participation rate 69.4%) were screened by casual glucose and glycated haemoglobin measurement, followed by oral glucose tolerance testing (OGTT) if one or both were elevated. The minimum prevalence rate of diabetes in the study sample was 17.2 +/- 3.3% in men and 12.5 +/- 2.2% in women (since not all patients underwent OGTT). The rate was only significantly higher in men than women in the 70-74 year age group (P less than 0.01). The combined age-adjusted prevalence rates for the New Zealand elderly are estimated to be 9.9% known diabetes, 5.0% previously undiagnosed, with the total prevalence rate 14.9%. Newly diagnosed subjects had a significantly higher body mass index than known diabetic or non-diabetic subjects (P less than 0.01). Eighty-two percent of newly diagnosed subjects had visited their general practitioner at least once during the previous 6 months. Measurement of glycated haemoglobin had a greater positive predictive value than casual blood glucose in the detection of new cases. There was no difference in frequency of attendance with general practitioners or in hospital admission rates between non-diabetic patients, or those with known or newly diagnosed diabetes. This study suggests that diabetes mellitus may be a prevalent disorder amongst the New Zealand elderly. PMID- 1600852 TI - Comparison of the effects of nilvadipine and captopril on glucose and lipid metabolism in NIDDM patients with hypertension. AB - Changes of glucose and lipid metabolism in NIDDM hypertensive patients during treatment with a new dihydropyridine derivative, nilvadipine, were examined by a randomized, crossover study comparing the results with those elicited by captopril in 18 patients for 12 weeks each. Nilvadipine (8 mg per day) and captopril retard (75 mg per day) caused a sufficient decrease in blood pressure without changing the pulse rate. Nilvadipine and captopril did not significantly change fasting plasma glucose, hemoglobin A1c, serum cholesterol, triglycerides, high-density lipoprotein cholesterol or apoprotein A-I, A-II and B levels in either of the 12-week treatments. In 75-g oral glucose tolerance tests carried out three times in each patient (before treatment and after 12 weeks of treatment with each drug), changes in plasma glucose and serum insulin levels were not significantly different among the three tests. These results demonstrate that nilvadipine as well as captopril are antihypertensive drugs without adverse effects on glucose and lipid metabolism in hypertensive patients with NIDDM. PMID- 1600853 TI - In search of predictive markers of remission from insulin dependence in type 1 diabetes: a preliminary report. AB - We studied 18 newly diagnosed diabetic patients (8 males and 10 females, aged 18 26 years, within 10-120 days from the onset of symptoms) who were submitted for 15 days to intensive insulin therapy performed via subcutaneous insulin infusion (CSII). We investigated some metabolic and immunological parameters in order to identify a possible marker to predict the selection of patients potentially more responsive to CSII treatment for the remission of type 1 diabetes. In accordance with the International Diabetes Immunology Group we considered clinical remission as being the withdrawal of insulin therapy for at least 3 months. In order to assess beta-cell function a fasting and post-prandial serum C-peptide, blood glucose and HbA1c were performed on all patients before, and 3 days after, the discontinuation of CSII. Islet cell antibodies were determined in all sera by indirect immunofluorescence. Analysis of T-lymphocyte subpopulations was carried out before starting the therapy. The following monoclonal antibodies were used: CD4, CD8, CD57, CD25, HLA-DR. The levels of C3 and C4 and serum IgG, IgA and IgM were also evaluated. After CSII, 11 of 18 patients showed remission. At the beginning of the study we observed no major difference in metabolic parameters between the two groups. Interestingly, the patients who exhibited remission presented a statistically higher percentage of positive cells for CD57, HLA-DR and CD25 surface antigens, significantly lower C4 levels and CD4/CD8 ratio and significantly higher IgG levels compared with patients who did not show any remission.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600854 TI - Risk factors for progression of microvascular complications in the Stockholm Diabetes Intervention Study (SDIS). AB - Ninety-six patients with insulin-dependent diabetes mellitus (IDDM), non proliferative retinopathy, normal s-creatinine and previously high blood glucose levels were followed for 5 years. In multivariate analyses the mean HbA1c level (14 values during 6-60 months) was significantly correlated with albumin excretion level (P less than 0.01), retinopathy (P less than 0.001), motoric and sensoric nerve conduction velocities (P less than 0.01), thermal threshold on the foot (P less than 0.01), the respiratory sinus arrhythmia (P less than 0.01), the valsalva ratio (P less than 0.05) and the orthostatic blood pressure reaction (P = 0.05) after 5 years. Neuropathy was related to both the HbA1c value at baseline (P less than 0.05) and the mean HbA1c value during the study (P less than 0.001). Smoking habits were correlated with the total number of complications deteriorating (P less than 0.05), as was HbA1c during the study (P less than 0.001). Patients with an initial HbA1c of 9% or more could reduce the risks for deterioration of microvascular complications to 10-15% by reducing their HbA1c below this level. PMID- 1600855 TI - Glycaemic control and progression of nephropathy in proteinuric NIDDM patients. PMID- 1600856 TI - Islet-cell antibodies and endogenous insulin secretion in Sudanese diabetic children. AB - Cytoplasmic islet-cell antibodies (ICA) and endogenous insulin secretion were studied in 46 Sudanese children (mean age 11.6 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM). Islet-cell antibodies were detected both by the indirect immunofluorescence (IF) and complement fixation (CF) methods. Endogenous insulin levels were measured as C-peptide concentration using radio-immunoassays. The degree of metabolic control of diabetics was judged by the presence of diabetic ketoacidosis (DKA) at onset, glycated haemoglobin (HbA1c) level and insulin requirement, expressed as dose per kg body weight per day, at the time of presentation. Twenty-nine patients (63%) had either IF-ICA or CF-ICA or both in their sera. These figures are significantly higher than those reported for African populations. Islet-cell antibody positive patients had significantly lower C-peptide concentration, higher HbA1c level, higher insulin requirement and higher prevalence of ketoacidosis at presentation. Furthermore, the C-peptide levels were higher in CF-ICA positive patients than in subjects who showed only IF-ICA positivity. Our findings show a clear association between ICA and severity of diabetes at clinical onset and also suggest that the presence of CF-ICA at or shortly after diagnosis of IDDM is indicative of preservation of some functioning beta-cell mass. PMID- 1600857 TI - Height is an independent risk factor for neuropathy in diabetic men. AB - Height may increase the risk of diabetic polyneuropathy, but previous studies are inconclusive. Our purposes were to further examine the hypothesis that height (HT) is an independent risk factor for diabetic polyneuropathy and to determine which electrophysiologic measures are influenced by HT in diabetic subjects. We studied 170 Japanese American men (ages 43-73 years, mean 61) including: 69 diabetic men (mean HT 166 cm), 54 normal men (mean HT 167 cm), and 47 men with impaired glucose tolerance (IGT) (mean HT 164 cm), measuring 28 nerve conduction study (NCS) parameters. We used data from normal men in developing regression models to adjust NCS parameters for HT, age, and temperature. Factor analysis was employed to reduce the 28 NCS parameters to five physiologically meaningful factors, one of which, a factor representing median and peroneal sensory amplitudes, was significantly correlated with HT (r = -0.38, P = 0.0011) in diabetic men; taller subjects having smaller sensory nerve amplitudes. No significant correlation was found between this factor and body mass index. This factor had no correlation with HT in normal or IGT men. Our data do not confirm previous reports of associations between HT and slowed motor conduction velocities in diabetic subjects. This study does, however, support the hypothesis that HT is an independent risk factor for sensory polyneuropathy in diabetic subjects. PMID- 1600859 TI - [Chromosome aberrations in somatic cells in gunshot injuries]. PMID- 1600858 TI - [Polymorphism of proteins and blood groups in people with various types of wound healing: genetic distances and correlation]. PMID- 1600860 TI - [Use of mathematical modelling for calculating the optimal plan for administration of the antineoplastic agent thiophosphamide]. PMID- 1600861 TI - [Preparation and characteristics of a clonal library of mononucleosomal DNA from human cell chromatin and its use for studying the similarity of nucleosomal DNA to histones]. PMID- 1600862 TI - [Interaction of transcription factors of the NF-kappa B/rel family with DNA leads to significant bending of it at binding segments]. PMID- 1600863 TI - Inhibition of EGF-induced cytoskeletal change in A431 cells by inhibitors of phosphatidylinositol turnover. AB - Expression of epidermal growth factor (EGF) receptor is often increased in various human carcinomas. Therefore, inhibition of the EGF/EGF receptor-induced signaling pathway may help to suppress these carcinomas. In the presence of Ca2+, EGF induces elongation of A431 cells in approximately 30 min. The cell elongation was shown to be accompanied by a reorganization of actin filaments. These phenotypical changes were specifically inhibited by a tyrosine kinase inhibitor, erbstatin, and inhibitors of phosphatidylinositol (PI) turnover such as psi tectorigenin and inostamycin. The amount of filamentous actin was increased by EGF, which was also inhibited by these compounds. Long-term treatment of A431 cells with EGF induced the disappearance of cytoskeleton and aggregation of the cells, which was again inhibited by the PI turnover inhibitors. Thus tyrosine kinase and phosphatidylinositol turnover inhibitors were shown to inhibit the signaling pathways of EGF-induced cytoskeletal organization of A431 cells. PMID- 1600864 TI - Modifications of "A cells" in the development of experimentally induced pancreatic ductal adenocarcinoma: an ultrastructural and immunohistochemical study. AB - In the hamster-BOP model, modifications occur in the endocrine portion of the pancreas during the induction of well-differentiated ductal carcinomas. In the present work, using immunohistochemical techniques it was possible to observe that the A cells in preserved islets and in the initial phase of the carcinogenic process were localized in the peripheral part of the islets. In animals with tumours, A cells were found to form part of the tumour glands and/or the tumoral stroma; this localization was seen to depend on the developmental phase of the tumour. A focal dispersion of A cells was observed in the animals with ductal carcinoma. PMID- 1600865 TI - Evaluation of the therapeutic efficacy and tolerability of levocarnitine propionyl in the treatment of chronic obstructive arteriopathies of the lower extremities: a multicentre controlled study vs. placebo. AB - The treatment of symptomatic chronic obstructive peripheral arteriopathies is a difficult task since it requires the prolonged administration of drugs which are often unable to correct the various pathogenetic factors reponsible for the disability. The authors, on the basis of recent studies demonstrating the rheological and vasoactive as well as metabolic activities of levocarnitine propionyl, have decided to use this substance in the treatment of arteriopathics affected by intermittent claudication. Levocarnitine propionyl administered orally to 142 arteriopathics affected by intermittent claudication was responsible for a marked increase in initial as well as absolute walking distances. It is particularly important to note that these clinical results were obtained primarily due to the metabolic activities of levocarnitine propionyl. PMID- 1600866 TI - Cellular electrophysiological effects of platelet-activating factor (PAF) and its antagonist BN 52021 in cardiac preparations. AB - The effects of PAF and its antagonist BN 52021 were studied on the transmembrane action potential (AP) in atrial and ventricular papillary muscles of guinea-pig. PAF (10(-11)-10(-7) M) did not modify the resting membrane potential (RP) nor the maximum rate of depolarization (Vmax) either in atrial or in ventricular fibres. At 10(-11) M, PAF increased the amplitude of AP both in atrial and ventricular muscles. the repolarization phase was dose-dependently shortened in the case of atrium, while the duration of ventricular AP was somewhat increased. The K+ channel blocker 4-aminopyridine (10(-3) M) prevented the effect of PAF on the duration of atrial AP. BN 52021 (10(-7) M to 10(-5) M) produced a significant shortening of the duration of atrial AP and did not modify the other parameters. In papillary muscle up to 10(-6) M, it increased both RP and the amplitude of AP and caused a dose-dependent shortening of the repolarization. Neither PAF (10( 11) to 10(-7) M) nor BN 52021 (10(-5) M) was able to induce slow AP in guinea-pig atrial and ventricular preparations depolarized by 25 mM K+ Tyrode solution. PAF did not modify the slow AP elicited by isoprenaline (5 x 10(-7) M). The present findings suggest that neither PAF nor BN 52021 affects slow inward Ca2+ current but their effects on other ionic currents, e.g. K+ currents, may be important. PMID- 1600867 TI - [De novo malignant tumors during drug immunosuppression. The findings following 1245 cadaveric kidney transplants in 1080 patients]. AB - Thirty new malignant tumours were found in 1080 patients (634 men, 446 women; mean age 37.6 +/- 13.6 years) after a median follow-up period of 5 years following 1245 cadaveric kidney transplantations performed between 1972 and 1990. The mean dialysis period before transplantation had been 4.0 +/- 3.1 years. Regarding the type of tumour, carcinomas were by far the most frequent, while there was only one lymphoma. The annual malignancy incidence for renal transplant patients was 0.5%. This is 3.5 times higher for men and 4.2 times for women than in the normal population. Immunosuppression with azathioprine and/or antithymocytic globulin (n = 395) produced the same malignancy incidence (0.54%) as with cyclosporin (n = 685; 0.60%). On the other hand, malignant tumours occurred much earlier under cyclosporin than under azathioprine/antithymocytic globulin (27 and 68 months, respectively). PMID- 1600868 TI - [Acute schistosomiasis in travellers to the tropics]. AB - Two of three members (a 29-year-old man [case 1] and a 26-year-old woman [case 2]) of a tourist party to the tropics (Mali) developed a high fever (less than or equal to 40 degrees C), headache, cough, weight loss (less than or equal to 5 kg) and tiredness 3-4 weeks after returning to Germany. In case 1, acute schistosomiasis was tentatively diagnosed as the cause because he reported an attack of dermatitis after exposure to fresh water in an endemic schistosomiasis region and had marked eosinophilia (2118/microliters; 28%) on admission. Serological tests were positive (ELISA with adult antigen, O.D. 0.65 [normal less than 0.15]; with egg antigen O.D. 1.73 [normal less than 0.30], antibody titre in the immunofluorescence test 1:320 [normal less than 1:80]) supported the diagnosis and it was confirmed by demonstrating the parasite, Schistosoma mansoni, in stool but not urine. Findings in case 2 were similar. The third member of the group [case 3], a 58-year-old woman, was symptom-free, but tests revealed schistosomiasis. All three patients were treated with a single dose of Praziquantel (40 mg/kg). A second course of praziquantel (single dose of 40 mg/kg as well as 20 mg/kg three times daily for 3 days) became necessary in case 1, while in case 3 a further single dose of 40 mg/kg was given to ensure a parasite free state. A follow-up scheme is suggested: clinical examination with white cell and differential counts 1, 3, 6 and 12 months after treatment; three stool and/or urine examinations 3, 6 and 12 months after treatment. PMID- 1600869 TI - [Glossopharyngeal neuralgia with syncope]. AB - Eleven years after treatment of a tonsillar carcinoma by neck dissection, chemotherapy and radiotherapy, a now 26-year-old man had several syncopes, all preceded by burning pain in the area of the left ear with radiation to the throat and left tonsil. ECG monitoring revealed 3 degrees atrioventricular block with a slow idioventricular rhythm (34/min), as well as an asystole lasting 13 seconds. There were renewed syncopes even after pacemaker implantation. 24-hour blood pressure monitoring recorded pressures of 65/50 mm Hg, coinciding with symptoms of pain and dizziness. Being diagnosed as having glossopharyngeal neuralgia with cardiovascular involvement he was given carbamazepine, 400 mg three times daily, but without improvement. Because of this treatment failure the glossopharyngeal nerve was surgically divided, with partial but not complete regression of the symptoms. The patient declined the suggested further bilateral division of the upper vagal branches. PMID- 1600870 TI - [The therapy of primary aldosteronism]. PMID- 1600871 TI - [The diagnosis of mitral valve insufficiency by echocardiography]. PMID- 1600872 TI - [The "minimization" of surgical trauma]. PMID- 1600873 TI - [Beta 2-microglobulin]. PMID- 1600874 TI - ["Etiocholanolone fever"?]. PMID- 1600875 TI - [A cholesterol-lowering effect of garlic?]. PMID- 1600876 TI - [Collagen application after arterial puncture]. PMID- 1600877 TI - [Tha balloon dilatation of calcified heart valves]. PMID- 1600878 TI - Development of the limbic-hypothalamic cholecystokinin circuit: a model of sexual differentiation. AB - Reproductive behavior is the final outcome of the integration of appropriate gonadal hormonal stimulation with olfactory and somatic cues by the steroid sensitive limbic-hypothalamic neural circuit. Gonadal hormones sexually differentiate the structure and neurochemistry of this circuit during development. In adulthood, gonadal steroids continue to regulate the behavioral response of the animal through their effects on intercellular signalling in this limbic-hypothalamic circuit. Recently, the neuropeptide cholecystokinin has been demonstrated to be an important intercellular messenger, expression, distribution, levels, and receptors of which are regulated both during development and adulthood by the gonadal steroid environment. Studies on the development of sex differences using the cholecystokinin component of this circuit as a model have yielded insight into how gonadal steroids modulate the neurochemistry of the reproductively relevant limbic-hypothalamic circuit. Concentrating on this circuit and its role in reproduction, we will review the data about gonadal steroid effects on the distribution, expression, development, and physiology of cholecystokinin and its receptors. PMID- 1600879 TI - Monoclonal antibodies as probes for the analysis of the secretory ependymal differentiation in the subcommissural organ of the chick embryo. AB - Monoclonal antibodies directed against components of the subcommissural organ (SCO) of the chick embryo were produced by immunizing mice with SCO homogenate. In three series of production, 788 hybridomas were screened by immunofluorescence microscopy. Four hybridoma cell lines producing antibodies that specifically recognize both SCO cells and Reissner's fiber (RF) were selected and cloned. Using these immunological probes, the ontogenetic development of the SCO and RF was investigated in the chick embryo. Immunoreactive material could be detected in the SCO anlage from stage 17 on and RF was first observed in the central canal of the thoracal part of the spinal cord in 10-day-old embryos. Monoclonal antibodies can be useful as markers for analyzing molecular mechanisms involved in the specific function of these ependymal cells. PMID- 1600880 TI - Effect of colchicine on ganglioside composition of rat primary culture neurons. AB - Developmental changes in gangliosides in the course of neurite outgrowth were examined in dissociated fetal rat cerebral neurons in culture. About a 2-fold increase in ganglioside levels was seen with the progression of neurite formation for up to 24 h in predominantly neuronal cultures. Ganglioside patterns appeared to be unchanged during the first 24 h, subsequently consisted of higher amounts of GD3 and b-series gangliosides (such as GD1b, GT1b, and GQ1b), and lower amounts of a-series gangliosides (GM1 and GD1a). Although the addition of colchicine to the cell growth medium inhibited neurite outgrowth in developing neurons, little if any differences in ganglioside patterns were found between control and colchicine-treated cells. Ganglioside levels decreased slightly in colchicine-treated cells in agreement with the decrease in cell attachment to culture dishes. Although colchicine treatment 8 h after plating caused complete retraction of formed neurites, the ganglioside level of the cells continued to increase during the following 16-hour incubation. Thus, the data suggest that ganglioside synthesis in differentiating neurons does not primarily accompany the expansion in cell surfaces due to neurite formation, and raises the possibility that a large proportion of gangliosides is retained in intracellular compartments. PMID- 1600881 TI - Neostigmine-induced characteristics of spontaneous activities and evoked muscle potentials in rat gastrocnemius and soleus muscles. AB - Using concentric electrodes, spontaneous activities and evoked muscle potentials were recorded from medial gastrocnemius (MG) and soleus (SOL) muscles of Wistar rats about 60 days old. When neostigmine methylsulfate was injected, spontaneous activity such as motor unit discharges occurred in a burst in the MG muscles, in contrast to few activity before the injection of this drug. In the SOL muscles, only single spikes were sometimes observed after it. In coincidence with burst discharges, some oscillations were definitely observed following the main component of MG potentials evoked by single stimuli to a sciatic nerve, whereas only slight deflections could be detected in SOL potentials. Thus, different modification of spontaneous activities and evoked muscle potentials were induced in MG and SOL muscles by the injection of neostigmine methylsulfate. PMID- 1600882 TI - Microanatomy and number of nerve fibres of the lower intercostal nerves with respect to a nerve anastomosis. Donor nerve analysis. I. (IV). AB - A human intercostal nerve has about 10,000 myelinated nerve fibres, of which about 1000 to 2000 are motor. At about the axillary line the nervus intercostalis splits into the ramus cutaneous lateralis and a deep branch to the musculus rectus abdominis and other muscles. The ramus cutaneous lateralis consists of 2 skin branches of about 3000 nerve fibres and a muscle branch to the musculus obliquus externus of about 400 to 1100 nerve fibres. The deep branch to the musculus obliquus internus, the musculus transversus and the musculus rectus abdominis and the anterior skin consists of about 2500 to 7000 fibres of which 400 to 1700 are skin fibres. There is indication that the muscle branch to the musculus obliquus externus has about 50% motor fibres. The intercostal nerve is, as it splits after about 20 cm into 4 branches, a suitable donor of at least 2 different muscle functions and a skin sensible function for a direct nerve anastomosis. A crude model for calculating matching probabilities of motor and sensory fibres between donor and acceptor nerves is introduced. Besides the importance of having enough donor nerve fibres, it is calculated that the small amount of motor nerve fibres can be best used if muscle branches of the donor nerves are connected to muscle branches of the acceptor nerves. Because of the separation between normal laboratory animals and humans on the phylogenetic scale, differences in regeneration and plasticity are discussed. PMID- 1600883 TI - Number of fibres and fibre diameter distributions of nerves innervating the urinary bladder in humans. Acceptor nerve analysis. II.(IV). AB - 1. The nerves innervating the urinary bladder were analysed morphometrically for their nerve fibre number and their nerve fibre group composition. 2. The nervi pelvini contained about 4000 myelinated nerve fibres, the nervi rectales inferiores and perineales 1700 and the nervus hypogastricus 2000 fibres. 3. An upper limit for somatic sphincteric alpha 2-motoneurons was 30 in the nervi rectales inferiores and perineales. The nervi pelvini contained about 400 fibres with diameters between 7 and 15 microns and myelin sheath thicknesses between 1.8 and 2.3 microns. Some of these thick nerve fibres could innervate the external urethral sphincter. It is estimated that the number of efferent parasympathetic fibres in the nervi pelvini on one side was about 800, which makes about 20% of all the myelinated fibres of the nervi pelvini. 4. It is discussed that efferent fibres to the external bladder sphincter may lead through the nervi pelvini or a direct branch instead of leading through the pudendal nerve. 5. In the Clinical Implications it is summarized that one intercostal nerve (9000 afferents, 1000 efferents) with its dissectable skin (3000 aff), muscle (300 aff, 300 eff) and mixed branches (2500 aff, 1500 eff) contains enough myelinated fibres for a reinnervation of the detrusor (3200 aff, 800 eff), the external anal and bladder sphincters (30 aff, 30 eff), the mucosa of the urethra, trigonum vesicae and anal canal (200 aff) and the lower sacral skin (6000 aff) on one side if one intends to restorate urinary bladder function in paraplegia by a nerve anastomosis. Reasons for a loss of plasticity of the injured spinal cord are given. PMID- 1600884 TI - Nerve conduction study, electromyography and somatosensory evoked potentials in non-Friedreich early onset cerebellar ataxia. A comparative study with Friedreich's ataxia and late onset cerebellar ataxia. AB - Electrophysiological findings in 14 patients with non-Friedreich early onset cerebellar ataxia are reported. Nerve conduction studies showed reduction of sensory action potential amplitudes in 7 cases associated in 3 with a decrease of sensory conduction velocities. Six subjects also exhibited a chronic neurogenic pattern to standard needle electromyography. Motor conduction velocities were normal in all cases; only two cases showed an increase in distal motor latencies. Short-latency somatosensory evoked potentials following median nerve stimulation revealed a prolonged central conduction time (N13-N20 interpeak latency) in 7 cases, compatible with supraspinal damage of the somatosensory pathways. These electrophysiological data are compared with those obtained in two reference groups of patients, respectively affected by Friedreich's ataxia and olivo-ponto cerebellar atrophy. PMID- 1600885 TI - Silent periods in the abductor pollicis brevis muscle in patients with Parkinson's disease. AB - Silent periods in the abductor pollicis brevis muscle, produced by electrical stimulation of the median nerve at the wrist or the palmar side of the index finger, were studied in 14 patients with Parkinson's disease (PD) and eight control subjects. Prior to the stimulation, background electromyographic activity showed no differences between normal subjects and patients with PD. Following the H-reflex after median nerve stimulation, two suppressive phases were observed: early (SP1) and late (SP2). Electrical stimulation of the palmar side of the index finger elicited two suppressive phases at almost the same latencies. The latency and duration of SP1 and SP2 and the degree of SP1, produced by electrical stimulation of the median nerve and the palmar side of the index finger in patients with PD, were normal. The degree of SP2 produced by electrical stimulation of the palmar side of the index finger in patients with PD was lower than that in normal subjects, although the degree of SP2 produced by median nerve stimulation in patients with PD did not differ from that in normal subjects. Suppression produced by cutaneous stimulation in the Parkinsonian hand may be low. PMID- 1600886 TI - Relation between the motor units recruitment threshold and their potentials propagation velocity at isometric activity. AB - The relationship between the propagation velocity of the excitation along the muscle fibers of the motor units (MUs) and their threshold of recruitment at different level of isometric voluntary contraction was investigated. The threshold of recruitment was measured by the value of the muscle force, expressed in percents from the maximal voluntary contraction (MVC) at which the first impulse of the MU appeared. A wire subcutaneous branched electrode was used to select the potentials from a single MU. The selected in this way MU impulses were used as a trigger to average two electromyographic (EMG) signals picked up by means of two monopolar surface electrodes with small leading-off areas mounted on a common plate at a distance of 10 mm from one another. The propagation velocity of the extraterritorial potentials of the MUs increased non-linearly with the increase of the recruitment threshold. The relationship was fitted as V = square root of a+b.theta, where v is the propagation velocity, theta is the threshold of recruitment and a and b are constants. The consideration of the velocity of propagation as a "size principle parameter" was discussed and the limitations of the latter are pointed out. PMID- 1600887 TI - Posterior interosseous nerve neuropathy. Clinical and electromyographical aspects. AB - A clinical-EMGraphic examination was carried out in 37 patients with posterior interosseous nerve neuropathy: 5 cases had a traumatic origin, 4 iatrogenic, and 28 non-traumatic. One of the non-traumatic cases had a lipoma, and another had chondroma. In the other cases, nerve entrapment at the level of the arcade of Frohse could be presumed. Acute or chronic onset of the deficit was probably due to repeated pronation-supination hand movements. A motor deficit in finger extension together with a radial deviation of the wrist, was typical. Surprisingly about 50% of the non-traumatic cases showed some sensory disturbance at the forearm, wrist or hand. EMG examination was useful to establish the entity and topography of the deficit. Follow-up was carried out in 27 cases (3 traumatic, 2 iatrogenic and 22 non-traumatic). Even if spontaneous recovery is possible, though infrequent, in non-traumatic cases with marked deficit surgery gave the most satisfactory results, especially when onset had been acute and operation was performed within nine months of onset. PMID- 1600888 TI - Somatosensory evoked potentials from distal, middle and proximal lower limb stimulation. PMID- 1600889 TI - Frequency of ulnar-to-median nerve anastomosis. PMID- 1600890 TI - [Mortality survey of treated mentally ill patients. Methodological reflections]. AB - All the studies performed in many industrialized countries have shown that the mortality-rates of mentally-ill patients are higher than expected, despite of a recent trend indicating a diminishing difference by comparison with control groups (review in Corten et al). In France, the works by Casadebaig and Quemada focused on the mortality-rates of psychiatric in-patients from 1968 to 1982 cannot unfortunately be performed nowadays because of an administrative change in the nation-wide death-registration. This is the main reason for the purpose of a longitudinal study on this topic for the next years in our country. The chief goals are concerned with public health and with analytical epidemiology: defining the Standardized Mortality Ratios (SMR) globally and by cause of death for the most typical clinical groups. Methodology and feasibility. The main methodological issues have to be examined first before implementation. Theoretically, one should wait that a multicentric longitudinal survey could be representative of the whole population of french mentally in and out-patients. Actually, this study will be more likely performed with collaborative centers agreeing for data-collection; and secondly, it will be necessary to control that these collaborative centers do not differ significantly from the other public psychiatry-departments for the main variables that may influence the mortality rates. The definition of cases and their identification will be done according to the International Classification of Disorders (ICD) considering its ninth and tenth revision. This research also needs to include a large number of patients because of statistical constraints.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600891 TI - Excessive mortality of hospitalized mentally ill patients (1968-1982). An out dated problem? PMID- 1600892 TI - [Epidemiologic surveys in the field of drug abuse]. AB - Among the various approaches used to study behaviours of use and abuse of drugs, epidemiology is now being called upon to direct its attention to two other approaches. Firstly, it should provide a more global view of subject groups than the specific descriptions of a few specialized centres. Secondly, it should take part in studies assessing public health policies for drug addiction. In relation to procedures used by epidemiologists in other fields of health sciences, the distinctive features of drug addiction need limitations and adaptation of methods. In France, anonymity and free health care are guaranteed to all drug addicts who request them. The direct consequences of this legislation is the absence of a drug addict register, unlike in other countries, such as Great Britain. There are no either registers nor survey data base from which representative samples can be constructed. Moreover, since those definitions used are multicriteria definitions, the assessment of a case on a drug addiction scale is in practice usually highly subjective and associated with the particular orientations of a clinical team or of a school of thought, because the notion of dependence is not used in the same way. Since drug addiction develops beyond adolescence and has social and/or medical consequences, specialized or non specialized public health services or prisons are the main areas of observation for epidemiologists. Surveys are conducted through teams specialized in the treatment of drug addicted volunteers. The anonymity of centres is guaranteed by the INSERM and the centres themselves guarantee the anonymity of subjects studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600893 TI - [Alexithymia. Evaluation, quantitative and clinical data]. AB - Alexithymia is a concept created by Sifneos in 1972 to describe a disturbance in affective and cognitive functions characterised by an inability to find words to describe feelings or emotions. The term "alexithymia" is derived from the Greek and means "no words for feelings". The salient clinical features of alexithymia include difficulties recognizing and verbalizing feelings, endless description of physical symptoms instead of emotions, concrete speech and thougth closely tied to external events, paucity of fantasy life. Precisely, alexithymia is an inability to associate one's visual image, thoughts and fantasies with a specific emotional state. For Sifneos, "emotions" and "feelings" are different facts. He differentiates "visceral emotions" (biologic side of the affect and lying in structures of the limbic system as the hippocampus and the amygdaloid complex) and "feelings emotions" (psychologic side of the affect). For him, animals experience "visceral emotion", but only human experience "feeling emotions". Alexithymia is regarded as one of several possible risk factors that seem to increase the susceptibility to physical disease. Alexithymia describes some psychological features which has been initially described by Marty and Psychosomatic French School: a specific cognitive style characterized by a lack of absence of fantasies and a preoccupation with the minute details of external events ("pensee operatoire"). Alexithymia is a difficult concept to operationalize and only few instruments are sufficiently reliable and valid. Several scales are used to measure alexithymia but only the Beth Israel Questionnaire (BIQ) and the Toronto Alexithymie Scale (TAS) can be regarded as having sufficient psychometric properties. The first questionnaire, the BIQ--a scale created by Sifneos--, is the most widely used instrument which is a 17 items forced-choice questionnaire completed by the interviewer. The TAS is a 26 items self-report measure rated on a five-point Likert scale. The Shalling Sifneos Psychosomatic Scale (SSPS) and the M.M.P.I. Alexithymia Scale lack of validation and reliability. Furthermore the SSPS and the MMPI AS show little or no relation with BIQ or with TAS, thus limiting the comparability and generalizability of results from the studies that use them. The TAS is considered as internally consistent and to have a stable, replicable factor structure. Other measures as content analysis test, projective test (Rorschach, T.AT., SAT9) or others self-assessment questionnaires are not frequently used.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1600894 TI - [Research on psychotherapies. Methodology]. AB - "Assessment" (of outcome and of factors of outcome) and "psychotherapy" are first defined. Although the aims of these surveys are deeply varying depending on their initiators (therapists or administrations), they share the same objects and the same methodological problems. This common problematic is specific, different from those prevailing for epidemiology or therapeutic trials; it also varies depending on the psychiatric and cultural background (for instance, depending on the side of the ocean). The choice of variables is discussed for objects (patients, families, therapists, institutions), sources (self and hetero-questionnaires) and exploratory levels (from symptoms to subjective quality of life). This leads to the choice of instruments, the interest of open ended questions and specific modalities of responses being emphasized. After a discussion of several methods of outcome assessment, the study of factors of change includes a comparison of the naturalistic and experimental approaches. Although these studies encounter some risks and limitations, they have an obvious clinical interest. PMID- 1600895 TI - [Evaluation method of social rehabilitation of adults who had suffered infantile psychoses]. AB - This study attempts to find out the outcome of psychotic children as adults, essentially with regard to social adjustment, main prognostic variable. To avoid the biases of an institutional recruitment, our population was defined in a geographic area: the Herault department (2-4). In the international literature only 3 studies of outcome in adulthood (6-8) could be found. The procedure encountered many difficulties: geographic dispersion, lack of standardized assessment of social adjustment. The method used was chosen in order to compare with other studies. It describes: the present situation and psychiatric status of 47 persons, 17 to 24 year old (mean = 21 years); social characteristics with 6 variables: employment, school credits, living accommodation, leisure activities and interpersonal relationships, marital status, medical care utilization. A score of 0 (poor adjustment) to 3 (very good adjustment) was given for each of the previous variables. To make later analyses easier, we summarized these data into a single score: index of social adjustment. RESULTS Among the 47 persons, 41 have been located; 2 were dead. Most of them are young (18 subjects are 17 to 20 year old). 19 of them carry on special education or special vocational training. In specialized institutions, they are day-pupils or boarders depending on family possibilities. 8 persons are active: the level ranged from special job training to sheltered employment. 4 persons live in special centers for handicapped adults; according to their skills they perform or not some very easy work. 4 persons live in their family without any project.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600897 TI - [Unipolar and bipolar: the two mood disorders]. PMID- 1600896 TI - [Mortality of mentally ill patients. Review of the literature]. AB - Overmortality among psychiatric patients has been a regular observation from the XIXth century to nowadays. If the rates of mortality have decreased in these last fifty years, they still remain higher than in the general population Standardized Mortality Ratio (SMR) (two or three times greater than normal). The authors reviewed 53 recent articles from european, north american, japanese and israelian researches on this question. Most of them proceed from crossings between psychiatric case register and death-register, and concern inpatients only (Brook, Giel, Saugstad, Mortensen, Herman, Haugland, Rorsman, Sturt, Winokur, Zilber). Some take into account outpatients as well (Eastwood, Koranyi, Martin, Ribourdouille). SMR are calculated and comparisons are made between different groups by sex, age, diagnosis and cause of death. Those are usually divided into 2 categories: natural deaths somatic diseases) and unnatural deaths (suicides accidents). MAIN RESULTS: Among the patients, mortality rates are higher for men than women, but SMR are higher for women. The highest mortality relative risk is observed between 20 and 40 years of age. Except for three authors, unnatural deaths are not sufficient to explain overmortality. SMR for suicides and accidental deaths are decreasing with age; the relative risk is more important for outpatients, men, some specific diagnoses (affective disorders, acute schizophrenia) and during the first two years of the course of the illness. Suicide rates have been increasing among patients these last twenty years. Natural death is more frequent among patients with organic brain syndromes but is also in excess for the other patients. Cardiovascular diseases represent the first cause of mortality but infections (pneumonia-influenza) and metabolic diseases are over-represented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600898 TI - Major depressive episode: unipolar and bipolar II. AB - Major Depressive Episod (MDE) delimits a wide range of heterogeneous disorders. Nowadays, both for research and for therapeutic aims, precise characteristization of MDE subtypes are needed, different subtypes of MDE requiring individualized short, long-term and preventive treatments. As patients mainly seek for physician help during the full-blown depressive phase, we focused our study on patients presenting a major depression as the index episode. In order to attempt to isolate subtypes of the disorder relatively to the mood spectrum disease and to obtain a better clinical characterization of each, we have considered the role of soft indicators of bipolarity or of milder mood disregulations in distinguishing among subtypes of MDE; special attention was devoted to detect spontaneous or drug-induced hypomania, as well as to assess the hyperthymic or cyclothymic temperament, and family history for mood disorders. Data on prior course, characteristics of index episode, and familial aggregation of patients with Bipolar II Disorder support the autonomy of this condition. Differently from our previous analyses we considered Bipolar II with hypomanic episodes separately from U-HT unipolar with only hyperthymic temperament. The comparison between these two subgroups showed a higher percentage of males in the hyperthymics, longer duration of illness and a greater number of depressive episodes and hospitalizations in bipolar II with hypomania. Data from our analyses are exposed and discussed. PMID- 1600899 TI - [Mixed depressive syndrome]. AB - For a period of six months (april to october 1990) 361 manic-depressive in patients or out-patients were examined and treated. 178 patients (119 females and 69 males) were suffering from depression at examination time. Among them, 34 women and 11 men had mixed mood disorders with a symptomatology near that of typical depression (major depression, according to the DSM III-R criteria) but not of mixed bipolar disorder. The main symptoms were: dysphoric mood with irritability; internal tension, psychic and sometimes physical agitation; emotional lability; head crowded with thoughouts or thoughts that vanish too quickly; sleep disorders with initial insomnia or with frequent night awakenings; suicidal thoughts or attempted suicide with impulsiveness. These patients sustained severe suffering. They were in no way slow-minded but rather talkative and expressive. Antidepressant drugs increased agitation and insomnia, and in some cases, suicidal impulses. BZDs had limited efficacy but neuroleptics given in small doses, anticonvulsants and lithium gave very effective results. A limited number of electroshocks provided rapid improvement. In many respects, depression with delirium seems a more severe form of the above-described combined depressive syndrome and responds to the same treatments. We think that this mood disorder includes excitement as an important component, although this was not clearly evident. However, it is not easy to conceive this syndrome as a mixture of depressive and manic symptoms; it should rather be regarded as another specific mood condition, either permanent or transient, situated between the two other conditions. PMID- 1600900 TI - [Hypomania. Apropos of a cohort of young patients]. AB - The Zurich prospective epidemiological study included 591 twenty-year old subjects. At age twenty-eight, 457 of these people (228 males, 234 females) were re-examined and 415 of them at age thirty (197 males, 218 females). The DSM III-R definition of hypomania was modified. We found the following prevalences: 1.7% with hypomania, 3% with bipolar syndromes, 18.6% with major depression (including mood disorders) and 12.3% with short recurrent depression. Compared to male subjects, the risk of major depression was twice as high in female subjects but was roughly the same for the other groups. The study compares three groups of subjects: subjects with hypomania (UM), bipolar subjects (BP) and unipolar depression. Considerable differences were found depending on the levels of treatment, positive family histories for depression or hypomania and attempted suicides. The results show that the distinction between a subject with hypomania and a bipolar subjects is not clear. The ratings of the Hopkins Symptom Checklist scales (SCL 90-R), and of the FPI personality test (Fahrenberg et al., 1973) are presented and discussed. 12.7% of major depression cases were bipolar and 8.3% of short depressions were recurrent. In this sample of normal Swiss population, the ratio of bipolar to unipolar syndromes was approximately 1:5. PMID- 1600901 TI - [Unipolar-bipolar distinction. The genetic arguments]. AB - The latest classifications of mood disorders, such as DSM III and ICD 10, differ from previous ones by emphasizing the bipolar-unipolar distinction. This fairly recent distinction now enjoys a wide consensus. It is supported mainly by family studies. The first works originated from the school of Kleist and Leonhard and were quickly followed by reports by Perris and Angst (1966). Studies that followed the publication of DSM III confirm that the prevalence of bipolar mood disorders is twice as high among first-degree relatives of bipolar probands when compared with those of unipolar probands. Family studies suggest that unipolar and bipolar disorders are distinct but still share some degree of genetic overlap. Other genetic approaches such as twin and adoption studies are less conclusive. Recent linkage studies with genomic markers (RFLPs) cannot directly support the validity of the bipolar-unipolar distinction. They suggest the role of a major gene locus, notably in the Xq27-Xq28 region, only in a limited number of bipolar pedigrees. Most mood disorders might involve a polygenic environment; in this context, a more limited number of factors could be associated with the polarity of the disorder. PMID- 1600902 TI - Masked depression under the light of the new biological and nosological research. AB - Recent biological research in psychiatry has shown strong relationships between disorders apparently very different but sharing some common symptoms (target symptom perspective) or psychopathology (functional psychopathology perspective). The serotonin involvement in a wide range of conditions (such as depressions and other mood disorders, anxiety disorders, suicidal and aggressive behaviours, impulsive control disorders) has been explained through the common link of serotonin deficiency in disorders and behaviours characterized by a poor control of impulses (multi-impulsive disorders). Psychotropic drugs, mainly antidepressants, enhancing the serotonin metabolism have demonstrated a positive therapeutical effect on those conditions. But, the recent description of the so called Recurrent Brief Depressive Episodes raises the question if those serotonin related conditions could be diagnosed as mood disorders. In fact, during the 70's in a pre DSM III era, all of these disorders had been considered as forms of masked depressions. This perspective raises also the question about what should be considered as primary in the disorders described, the underlying disturbance of impulsivity or the underlying mood disorder. PMID- 1600903 TI - Brief unipolar depressions: is there a bipolar component? AB - Recurrent brief depression is now recognised separately in the international classification of diseases (ICD 10). The disorder is characterised by short severe bouts of depression which recur frequently but erratically. In our series of patients the median duration of the depression is 3 days, with two thirds lasting between 2 and 4 days. The severity is often marked with a mean MADRS score of 30, and the episodes recurred 20 times a year. The disorder is easily separated from major depression which lasts 2 weeks or more, although, there is an unfortunate overlap group with major depression superimposed on the recurrent brief pattern. Those with "combined depression" have a higher suicide attempt rate. There should be little overlap with dysthymia since on average only 20% of the time is spent depressed, whereas dysthymia requires a minimum of 50%. However, in practice the qualification of the time spent depressed is imprecise in dysthymia so there is potential for misdiagnosis. There is little overlap with bipolar illness. In our series with follow up of up to 15 years, the conversion rate to bipolar illness is low at 3%. Almost all of these were found to have combined depression, which suggests that the rate for pure recurrent brief depression is very low. These data suggest that pure recurrent brief depression is a unipolar depressive illness. PMID- 1600904 TI - The role of sleep and wakefulness in the genesis of depression and mania. AB - Disturbances of the sleep-wake cycle are frequently seen in affective illness and are exhibited in other psychiatric illness as well. In addition to being a useful research probe, manipulations of the sleep-wake cycle such as sleep deprivation (SD) and phase advance can cause depression to remit and thus can be used as alternative or as adjunctive to pharmacologic treatment. The antidepressant response to SD occurs whether antidepressant drugs are administered or not. However, there is some evidence that the concomitant use of antidepressants may prevent the relapses that occur after recovery sleep. Data from clinical investigations also indicate that disrupted sleep can trigger and intensify mania. Rapid cycling bipolar patients may be especially vulnerable to mania/hypomania after disrupted sleep or SD. Characteristic changes in body temperature have been recorded in sleep deprivation as well as in other antidepressant treatment modalities. Thermoregulatory physiology may therefore provide a framework for understanding the effects of sleep-wake manipulations in affective illness. PMID- 1600906 TI - [Dysthymic disorder and depressive personality]. AB - Depressive personality is a clinic category of Kurt Schneider psychopathic personalities. Despite definition of DSM III Axe II personality disorders criteria is Kurt Schneider' definition of psychopathic personalities, no depressive personality disorders is mentionned in Axe II. Axe I dysthymic disorder is a chronic state of depression with depressive traits. The hypothesis that some depressive personality disorders are included in this category cannot be rejected. More generally, DSM III classification regulation discriminate states, but, less operationally, traits which include affective variables with questionnable inter-rating reliability. PMID- 1600905 TI - [Development of the manic-depressive concept in German language psychiatry]. AB - German language psychiatry has had and still has much difficulty in getting rid of the dichotomy of endogenous psychosis as set by Kraepelin. The concept which makes a distinction between schizophrenic psychosis and manic-depressive psychosis grants the former a predominant position by applying Jasper's hierarchic rule: the presence of symptoms regarded as schizophrenic indubitably attributes the disorder to schizophrenia. Such classification, however, does not necessarily imply that schizophrenia and cyclothymia (word proposed by K. Schneider for manic-depressive psychosis) represent separate nosological entities. It is admitted that it is possible for each group to include diseases whose hereditary transmission is not necessarily due to the same genetic predisposition. Thus, German language psychiatry has well accepted the possibility that bipolar manic-depressive psychosis and unipolar depressions represent separate etiologies. For most German-speaking psychiatrists, however, the distinction between endogenous and psychogenic depressions still remains a current assumption. The distinction between these two types of depression is generally made with reference to an "endogenous item profile" or to a depressive endogenomorphous axial syndrome. Only a few authors have accepted the model of continuity between these two types of depression proposed by the London school. The Hamburg school gave a new dimension to the conceptualization of manic depressive psychosis by drawing attention on the existence of "rapidly alternating mixed states" which are much more common than the stable mixed conditions described by Kraepelin. On the basis of this concept and by questioning the validity of Jaspers' hierarchic rule, the Vienna school has considerably extended the limits of affectives psychosis to the detriment of the wide concept of schizophrenia described by K. Schneider.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600907 TI - [Current concept of mood disorders. Impact on the therapeutic management]. AB - The unipolar-bipolar distinction underlines the recurrence of the disorder (40 to 80% of unipolars and 95% of bipolars) and also the transition from one subtype to the other (10 to 15% of unipolars will become bipolars). Some semiological forms of depressive illness may give clues concerning the required management modalities. Depressions with psychotic features have a good response to ECT or to TCAs+neuroleptics. As other authors, Quitkin et al. find a good response of atypical depression to MAOIs. The comorbidity of mood disorders with personality disorders may be of poor prognosis. Akiskal suggested the presence of a depressive personality, Hudson and Pope suggest the notion of an affective disorders spectrum in which bulimia and OCD have a good response to serotoninergic antidepressants, whereas panic disorders have a good response to clomipramine, imipramine and MAOIs. Patient management should start with taking both the history of the disease and patient's previous treatment with a much precision as possible. Today the focus is on the particular progressive forms of resistant and chronic depressions, among which there are patients who have not received adequate treatment, and of rapid cyclers. The hypothesis of hypothyroidism in rapid cyclers has been suggested recently. Carbamazepine and Valproate seem to be efficacious in several recent open studies and in controlled for carbamazepine. The initiation of chemotherapy to prevent the recurrences of depression takes into account the unipolar or bipolar aspect of the mood disorder. Lithium has emerged as the prophylactic agent of choice in bipolar disorders, especially if the index episode is manic. Early prophylaxis is justified when the first episode is manic or after two depressive episodes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600908 TI - [5 cases of Cotard's syndrome in adolescents and young adults; symptoms of bipolar manic-depressive psychosis]. AB - The Cotard's syndrome existence among young adults is a recent notion. Its belonging to schizophrenia or mania depressive psychosis in under debate. From five observations of patients, we propose clinical and evolutive arguments allowing us to link up this symptomatology with bipolar manic depressive disorder. PMID- 1600909 TI - [Calcium channel blockers and dysthymic disorders. Recent data]. AB - The authors review the use of the calcium antagonists in the treatment of dysthymic disorders. Verapamil is mainly studied, but present researches focus on drugs with specific action on the CNS, particularly nimodipine. Their most constant therapeutic efficiency concerns hypomanic states; but their effect when prescribed alone remains inconstant on the manic states of bipolar disorders; in a preventive purpose, alone, or associated with lithium, their efficiency is real but inconstant. Their particular interest in dysthymic disorders is due to their absence of cognitive perturbations contrary to neuroleptics, and their less side effects than lithium. PMID- 1600910 TI - [Tardive mania]. AB - Rare but too often unrecognised, tardive mania offers a classic but moderate syndrome, rather mixed with delirious or deteriorated ideation, with chronicity. Prognosis is often serious. Either as a negation of the self's dispossession (psychoanalysis), or temporal and vital disconnection (phenomenology), tardive mania might be well conceived as the ultimate chance of a mystic enthusiasm (mythology). PMID- 1600911 TI - [Fluvoxamine. Study of treatment effect on a group of 189 hospitalized patients with depression]. AB - The study of a sample of 189 inpatients with the diagnostic of Major Depressive Disorder (DSM III-R) treated with fluvoxamine showed: a good compromise efficacy/tolerance in 75% of cases; an interruption of treatment in 25% of cases, schematically divided in early gastric intolerance and in late resistance. 2.5% of manic switches have been observed and contribued, with this pattern of good results, to confirm the major antidepressant activity and good tolerance of fluvoxamine. PMID- 1600912 TI - [Circadian rhythm of the axillary temperature in mood disorders. Prominent ultradian period in major thymic disorders]. AB - Axillary temperature was recorded in in-patients with affective disorders (DSM III-R). The results suggest that ultradian temperature rhythm could be the indice of an internal desynchronisation associated with acute episode of major affective disorders. PMID- 1600913 TI - [Fluvoxamine. Study of the relation between posology and plasma levels in a group of 80 hospitalized patients with depression]. AB - The study of the relationship between 198 plasmatic fluvoxamine dosages and posology has been done on a sample of 80 inpatients. It shows that plasmatic levels increase proportionally with posology p.o. In contrast, plasmatic levels seem to be independent from weight and age of inpatients. PMID- 1600914 TI - [Clinical study of 5 families with bipolar disorder]. AB - Five pedigrees of bipolar patients with at least two bipolar subjects on two generations have been identified in psychiatric departments of Nantes, Montpellier and Challans for linkage studies. In each pedigree, it was found one or more patients suffering from other conditions, like Borderline personality, Anorexia-bulimia, Mental retardation with dysmorphia, and Panic disorders. Mood disorders spectrum and therapeutic implications are discussed. PMID- 1600915 TI - [Triangular reflections on manic-depressive disorder. Apropos of 72 cases]. AB - In 72 cases of unipolarity or bipolarity depression followed at least three years the subsequent elements are questioned. What is the proportion of the different diagnostic types and what have been the most frequent life events of the first access, deaths, occupational and emotional failures, pregnancy, births, etc? In this population of patients between 23 and 80 years old reluctance or ignorance of the life events are important. We also investigated the level of our patients socio-professional insertion. As for the hetero ou auto aggressive acting out we tried to quantify them according to the chosen classification and the therapy followed by the patients of this group. In the hypothesis of a possible link with the hospital management evaluation and computer program we have briefly analyzed the incidence of lithium therapy on the number of hospitalisation days, without being able to draw a final conclusion as to the interest of this therapy in this very specific issue. PMID- 1600916 TI - [A specific prescription of lithium in different neurotic states or in normal subjects with transient dysthymic states]. AB - Among inapparent cyclothymic patients, love despair is frequently seen as basis or result of a severe thymic decompensation. Lithium is the recommended therapy for these critical states. PMID- 1600917 TI - [A 15 years' follow-up of use of lithium at the Department of Psychiatry of Marseille University. Data concerning the follow-up of 205 patients]. AB - The authors report descriptive data from a follow-up study of 205 patients taking lithium therapy and treated at the Department of Psychiatry (Marseille, France), during a 15 years period (1972-1987). Methods of investigation consisted in a detailed examination of their hospital and clinic case notes and in medical interviews of psychiatrists in charge of patients. 25 features have been selected in order to precise clinical and biological characteristics of patients: Diagnosis (INSERM, ICD9), family history of psychiatric disorders, illness course, salt used, serum and erythrocytes lithium levels, dose maintenance, additional medications, psychological and physical side effects, compliance with medication and clinical response. PMID- 1600918 TI - [Homicide is strongly correlated to depression and not to mania]. AB - Typical manic episodes could be the cause of penal infractions, usually benign. In contrast, forensic studies show a close relationship between depression, suicide and homicide. Killers (16-28%) are often depressed when they commit a crime. In the UK and USA, 4-35% of killers commit suicide immediately after their crime. Assessment of a depressed patient must include an evaluation of the risk of homicide as well as the risk of suicide. The past history of depression and suicidal attempts, the presence of depressive symptoms and suicidal ideas, are good predictors of impending danger of aggression and sometimes of homicide. PMID- 1600919 TI - The distinction between unipolar and bipolar mood disorders. A 25-years perspective. AB - The paper deals with a critical appraisal of the state of art of the distinction between bipolar (manic-depressive) and unipolar recurrent affective disorders. However already propounded several years earlier by Leonhard, a distinction between bipolar and unipolar affective disorders has first been taken into general consideration during the last quarter of a century. It is currently firmly established in the most widely accepted international classification systems, and is taken into account in the major psychiatric textbooks. Looking back at the evolution of this distinction, to which research work by the present author has greatly contributed, there are reasons to feel both satisfied and unsatisfied at the same time. Satisfaction arises from the fact that a distinction between bipolar and unipolar affective disorders has contributed to advance our understanding of the nosology of the depressive states, hence, contributing to a higher degree of homogeneity in the populations of patients in research. Dissatisfaction, instead, is born by the ever increasing widening of the scope of the concept of bipolar and unipolar to which current classification systems greatly contribute. PMID- 1600920 TI - Nutritional therapy in patients with liver cirrhosis. PMID- 1600921 TI - Loss of total body water and extracellular water assessed by multifrequency impedance. AB - Fat-free mass (FFM), total body water (TBW), extracellular water (ECW) and bioelectrical impedance at 15 selected frequencies, ranging from 1 kHz to 1350 kHz, were determined in 12 subjects before and 3 h after the use of a diuretic drug to induce loss of ECW. Weight loss and urine loss were recorded, and these were assumed to be equal to loss of FFM and TBW, respectively. From the excretion of sodium the amount of excreted ECW was calculated. Prediction formulae at all frequencies were developed for FFM, TBW and ECW from impedance data before the use of the diuretic drug. With these formulae the changes in FFM, TBW and ECW were predicted and compared with the losses of body weight, urine and ECW. At all frequencies FFM, TBW and ECW could be well predicted, with comparable values of explained variance and standard errors of estimate. However, the losses in FFM and TBW were significantly overestimated using the low-frequency impedance formulae. At higher frequencies the predicted losses were no longer significantly different from the weight and urine losses, respectively. The change in ECW was only adequately predicted at 1 kHz. Prediction formulae for ECW at higher frequencies underestimated the loss of ECW. It is concluded that multifrequency impedance offers the possibility of distinguishing between body fluid compartments and of assessing changes in body fluid compartments with a reasonable error. PMID- 1600922 TI - Riboflavin requirement of Filipino women. AB - The level of riboflavin intake that will correct riboflavin deficiency in seven non-pregnant and in twelve pregnant Filipino women was determined in order to reassess the adequacy of the current Recommended Dietary Allowance (RDA) for riboflavin in Filipinos. Increasing levels of riboflavin were given to the subjects who were rated as riboflavin-deficient based on an initial erythrocyte glutathione reductase activation coefficient (EGR-AC) of greater than or equal to 1.3 in screening. The minimum riboflavin requirement, defined as the intake of riboflavin required to achieve an EGR-AC of less than 1.3, was estimated from the regression of EGR-AC on riboflavin intake (mg/1000 kcal). The estimates of minimum riboflavin requirement from the non-pregnant women ranged from 0.16 to 0.42 with a mean of 0.35 +/- 0.09 (SD) mg/1000 kcal. For the pregnant subjects, the estimates of minimum riboflavin requirement ranged from 0.36 to 0.81 with a mean of 0.58 +/- 0.18 (SD) mg/1000 kcal. Adding 30% to the mean, to cover the upper limits of 97.5% of the population, the estimated RDA for non-pregnant women is 0.46/1000 kcal. This value is approximately equal to the 1976 Philippine RDA of 0.5 mg riboflavin/1000 kcal. For pregnant women, adding 30% to the mean minimum requirement of 0.58 mg/1000 kcal, the estimated RDA is 0.75 mg/1000 kcal or 1.75 mg/day computed at the energy allowance of 2350 kcal during pregnancy. This value is 25% higher than the current Philippine RDA of 1.4 mg/day for pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600923 TI - Nutrient intake and biochemical markers of nutritional status during long-term follow-up after total and partial gastrectomy. AB - Dietary intake and biochemical nutritional status was studied in patients who had undergone total gastrectomy (TG, n = 10) or partial gastrectomy (PG, n = 10) several years ago. The dietary intake of energy, macronutrients and micronutrients was very similar in the two groups and was also similar to the intake reported for healthy subjects in Sweden. The concentration of alpha tocopherol in serum was subnormal in the TG group and that of carotene in both groups of patients, and the values were also significantly lower in the TG group than in the PG group. This was probably due to fat malabsorption, since dietary intake was found to be adequate. The proportions of n-6 and n-3 polyunsaturated fatty acids in serum phosphatidylcholine were not significantly different between the TG and PG groups. Iron deficiency was found in three patients in the TG group. Three patients (two TG, one PG) had elevated serum alkaline phosphatase and one patient (PG) had subnormal cobalamin concentration. For ascorbic acid, folate, calcium, phosphorus, magnesium, zinc, copper and selenium, the serum concentrations were normal or close to normal. Although the stores of some micronutrients seemed smaller after total gastrectomy, no major differences in nutritional status were found between the TG and PG groups. For the demonstration of decreased micronutrient stores during long-term follow-up after gastrectomy, an extended profile of biochemical markers of nutritional status is recommended. PMID- 1600924 TI - Interrelations between growth, weaning and disease experience in Khartoum infants. AB - The monthly measurements of body weight and supine length from birth to 1 year of 203 infants in Khartoum were analysed to see whether growth characteristics affected the timing of weaning and the amount of illness experience. The study clearly shows that neonates who are long for their age tend to be weaned early, and this causes them to experience a greater average monthly 'illness experience' and slower subsequent growth. However, a multivariate analysis indicates that it is correlated environmental variables rather than length growth itself which primarily determines weaning age. Weight growth does not show these relationships but there is strong evidence that late weaning, independently of disease experience, promotes post-natal weight growth. PMID- 1600925 TI - Diminishing or increasing contrasts? Social class variation in Finnish food consumption patterns, 1979-1990. AB - The study examines whether social-class-based food consumption patterns changed in Finland during 1979-1990. The data were compiled by the National Public Health Institute in connection with a programme entitled 'Monitoring Health Behaviour among the Finnish Adult Population'. A questionnaire was sent annually to a random sample of Finns (N = 3400-5100, response rate 68-86%). This study was restricted to respondents 25-54 years old. Social class was defined by level of education (low, middle, high). Trends and variations in consumption patterns were studied by cross-tabulations and by fitting logistic regression models. The results show that the proportions of users of butter, high-fat milk and coffee sugar decreased during the study eriod whereas that of regular users of vegetables increased. Since the mid-1980s the shift towards 'healthier' food choices has accelerated among men, yet women are consistently more health oriented. Social class appears to be a significant determinant of food consumption patterns. Men and women of lower social class follow trends set by upper social classes with a time lag of about ten years. Along with an overall shift towards observance of dietary recommendations, social class differences in Finnish food consumption patterns have diminished, without, however, disappearing altogether. PMID- 1600926 TI - Differences between participants and non-participants in a population study on nutrition and health in the elderly. AB - In November 1988 a random sample of 435 men and women aged 70-75 years from the general population in Roskilde, a provincial town in Denmark, were invited to participate in a study of nutrition and health. Forty-six per cent of the total sample agreed to participate. The total sample could be characterized by socio economic variables and data on previous hospitalizations obtained from public registers. A subgroup of the non-participants could be further characterized by some of the topics under study using information obtained by telephone interviews. It was found that the non-participants differed from participants by selected health variables. More non-participants than participants had been hospitalized one year before contact. Telephone interviews with non-participants revealed generally poorer self-judged health and less-frequent eating of cooked meals compared with participants. The degree of bias introduced by this selectivity is estimated by weighting and by a minimum/maximum calculation. Review of participation in previous studies of nutrition and health in the elderly shows that problems with non-participation have been treated in various ways. It is concluded that consideration of factors discriminating between participants and non-participants is important for proper estimation of population parameters. PMID- 1600927 TI - Thymulin activity during very-low-calorie diet. AB - The potential use of thymulin levels as a sensitive and functional marker of energy deficiency was investigated in 13 obese women during a 3-week very-low calorie diet. Mean weight loss was 8.92 +/- 0.52 kg after 21 days of treatment. The patients were free from infection as assessed by serum orosomucoid and C reactive protein measurements. Serum albumin levels were not decreased throughout the experiment whereas transthyretin concentrations fell significantly during the first 2 weeks and remained fairly stable thereafter. Orosomucoid levels dropped only after 3 weeks of dieting. Serum zinc concentrations were within the normal range on admission and at the end of the experiment. Thymulin activity was not altered throughout the study, suggesting that this thymic hormone cannot be used as a functional marker of short-term energy restriction. PMID- 1600928 TI - Glycaemic and insulinaemic responses to orange and apple compared with white bread in non-insulin-dependent diabetic subjects. AB - To study the postprandial blood glucose and insulin responses to exchangeable amounts of simple and complex carbohydrates, eight non-insulin-dependent diabetic subjects consumed 227 g apple, 280 g orange or 50 g white bread on three separate days. The mean postprandial blood glucose response area to white bread (404 +/- 95 mM x 240 min) was significantly higher compared with orange (131 +/- 34 mM x 240 min; P less than 0.05) and apple (157 +/- 57 mM x 240 min; P less than 0.05). Thr glycaemic indices of the fruits were identical: 44 +/- 13 (orange) and 40 +/- 11 (apple). The low glycaemic response to orange and apple may be ascribed to the high content of fructose which is rapidly cleared and metabolized by the liver, without elevating the blood glucose. PMID- 1600929 TI - Dietary treatment of dermatitis herpetiformis. AB - Essentially all patients with dermatitis herpetiformis (DH) and dermal granular IgA deposits have a gluten-sensitive enteropathy as seen in coeliac disease. A gluten-free diet would normally restore mucosal morphology within months. The dapsone medication required to suppress the skin lesions could be gradually reduced and/or finally discontinued in most patients if they constantly adhere to the diet. The immunological reactions may also be reduced. The gluten-free diet could thus be successful both concerning manifestations from the skin and the gut. Although well known in dermatological literature, diet therapy in DH has attracted little interest in journals of nutrition. A survey of this causal diet therapy for the disease therefore seems appropriate. PMID- 1600930 TI - Calcium and iron absorption: mechanism of action and nutritional importance. AB - We investigated the inhibitory effect of calcium on iron absorption in 57 human subjects. Three studies suggested that the effect is not located in the gastrointestinal tract. The presence of phytate in a meal and formation of calcium-iron-phytate complexes is not a prerequisite for the inhibition. The relative increase in iron absorption by ascorbic acid was the same in meals with and without calcium, suggesting that calcium did not influence the balance between enhancing and inhibiting ligands in the gastrointestinal lumen. No inhibiting effect on iron absorption was seen when adding 3 mg calcium to 0.01 mg iron (molar ratio Ca/Fe = 420). Previous studies showing a marked inhibition by calcium had a lower molar ratio, but greater amounts of calcium were given. This suggests that a minimal concentration of calcium is needed to achieve an effect. The present results indirectly support our original hypothesis that the inhibitory effect of calcium on iron absorption is situated within the intestinal mucosal cells. The practical nutritional implications of the inhibitory effect of calcium are considerable since addition of milk, milkshake or cheese to common meals such as pizza or hamburger meals reduced iron absorption by 50-60%. It is recommended to reduce the intake of dairy products with the main meals providing most of the dietary iron, especially for those having the highest iron requirements i.e. children, teenagers and women at childbearing age. PMID- 1600931 TI - Energetic and metabolic cost of growth in Gambian infants. AB - The aim of the study was to measure the energy used for growth of healthy fullterm and breast-fed Gambian infants. The weight gain (WG) of 14 infants (mean age +/- SEM 17 +/- 1 d, weight 3.581 +/- 0.105 kg) was measured over a 2-week period; the energy intake (EI) from breast milk was assessed for 24 h in the middle of the study period by weighing the infant before and after each breast feed. On the same day, sleeping energy expenditure (SEE) and respiratory quotient (RQ) were measured for 30 min on five occasions through the 24-h period. EI averaged 502 +/- 25 kJ/kg.d, and SEE 230 +/- 6 kJ/kg.d; thus, an average of 272 kJ/kg.d were available for physical activity and the energy stored for growth. The total energy spent by infants while sleeping and for periods of physical activity was calculated to be 1.7 x SEE. The mean RQ measured on five occasions averaged 0.879 +/- 0.009. SEE was correlated with WG (r = 0.747, P less than 0.005), with a slope of the regression line of 5.5 kJ/g; this value can be considered as an estimate of the energy spent for new tissue synthesis in the resting infant. The efficiency of weight gain was lower in this study (67%) than in studies conducted on fast-growing preterm infants or children recovering from malnutrition. PMID- 1600933 TI - Energy balance in lactating undernourished Indian women. AB - An energy balance study was conducted in eight lactating poor-income Indian women from delivery to 6 months. Energy intake and expenditure were assessed for 7 days every month (30-37 days). Every month, basal metabolic rate (BMR) and milk ingested by infants was measured. An energy balance was computed. As a group these women were in energy balance, indicated by small body weight changes with respect to time. However, only two of these women were in a positive energy balance. Women with higher body weight lost more weight. Estimated mean energy intake was higher than energy expenditure. BMR showed a slight but not significant fall during the second month of lactation and was not different from the BMR seen in 13 non-pregnant, non-lactating women matched for body weight from the staff of the Institute. The energy cost of lactation was 2.3 MJ (549 kcal), a figure that justifies the Recommended Dietary Allowance for energy recommended by FAO/WHO/UNU (1985) and ICMR (1989). PMID- 1600932 TI - Lactation performance of rural Mesoamerindians. AB - Anthropometry, body composition and dietary intake of 30 lactating Otomi Indians of Capulhuac, Mexico, were studied to identify maternal factors which potentially limit lactation and thereby infant growth. Human milk production, milk composition, and maternal dietary intake, body weight, skinfold thicknesses, and body composition were measured at 4 and 6 months postpartum. The 2H2O dose-to mother method was used to estimate milk production and maternal total body water (TBW). Fat-free mass (FFM) was calculated as TBW/0.73. Body fat was computed as body weight minus FFM. Human milk samples were analyzed for energy, nitrogen, lactose and fat using standard analytical methods. Maternal diet was assessed by three 24-h intake recalls. Mean (SD) milk production was 885 (146) and 869 (150) g/d at 4 and 6 months, respectively. Milk concentrations of protein nitrogen (1.23 (0.17) mg/g) and lactose (66.6 (2.8) mg/g) were comparable to, but the concentrations of fat (22.2 (6.7) mg/g) and energy (0.54 (0.06) kcal/g) were lower than, values observed in economically privileged populations. Maternal height, weight, and BMI were 1.47 (0.06) m, 50.3 (6.0) kg, and 23.4 (3.1) kg/m2, respectively. Maternal TBW, FFM and body fat were 55.8 (4.6)%, 76.4 (6.3)%, and 23.6 (6.4)%, expressed as a percentage of body weight, respectively. Maternal energy and protein intakes averaged 1708 (338) kcal/d and 40 (10) g/d, respectively. Milk production was negatively correlated with maternal body fat (P = 0.006). Energy and fat concentrations in the milk of the Otomi women were positively related to their weight (P = 0.002), BMI (P = 0.05), and body fat (P = 0.004). Energy concentrations in milk were not related to rates of milk production (r = 0.24; P = 0.23). Nor was milk production or composition significantly associated with maternal dietary intake. Lactation performance of these Otomi women correlated significantly with maternal body size and composition, but not current dietary intake. PMID- 1600934 TI - Nutrients and contaminants in human milk from mothers on macrobiotic and omnivorous diets. AB - The effect of alternative dietary habits and prolonged lactation on the nutrient and contaminant concentrations in human milk was studied. The study sample consisted of mothers on macrobiotic diets, containing little or no diary products and meat, at 2-3 months postpartum (n = 9) and 9-13 months postpartum (n = 12), and mothers on omnivorous diets at 2-3 months postpartum (n = 10). Protein and zinc concentrations in breast-milk from macrobiotic mothers decreased with stage of lactation. After adjustment for stage of lactation, milk from macrobiotic mothers contained less calcium, magnesium and saturated fatty acids C15:0-C20:0, and more polyunsaturated fatty acids. Observed tendencies for lower protein and fat and higher lactose concentrations in the macrobiotic group were not statistically significant. Concentrations of vitamin B12, HCB and polychlorinated biphenyls (PCB 118, PCB 138, PCB 153 and PCB 180) were lower in the macrobiotic group. After adjustment for confounding variables, meat and fish consumption, but not dairy products, contributed to vitamin B12 concentrations. Meat and diary products strongly contributed to breast-milk concentrations of dieldrin and PCBs, fish to PCB 118, and smoking to DDT and dieldrin. Our findings suggest that breast-milk contamination could be reduced by abstinence from smoking and a moderate intake of animal products. However, risk of nutritional deficiencies rules out complete avoidance of meat, fish or diary products. Quantitative research on the effects of a reduced consumption of animal products, as well as smoking, on breast-milk contamination is warranted. PMID- 1600935 TI - Effect of caloreen supplementation on some haematological values and urinary iron excretion during protein-energy malnutrition. AB - The effect of caloreen (glucose polymer) supplementation on indicators of iron status during protein-energy malnutrition was studied. Sixty-four children with moderate protein energy malnutrition (PEM) were fed diets supplemented with caloreen or starch (control) for 14 days, following which iron status as packed cell volume (PCV), haemoglobin (Hb), serum iron, total iron binding capacity (TIBC), serum ferritin, and urinary iron levels were determined. Caloreen supplementation significantly increased (P less than 0.05). PCV, serum iron and serum ferritin and decreased (P less than 0.05) TIBC. Also, there was a tendency for Hb to increase and urinary iron to decrease in this group, but these changes were not statistically significant. Such changes were not observed in the starch placebo-supplemented group. It is concluded that caloreen supplementation to PEM children increases body iron status. These increases in the indices of iron status may contribute to an early recovery of anaemia associated with PEM. Prolonged supplementation of a regular diet with glucose early in the development of PEM may retard the development and severity of anaemia in children. PMID- 1600936 TI - Dietary habits and superstitions of rural Jamaican women during pregnancy. PMID- 1600937 TI - Identification of three adjacent amino acids of interleukin-2 receptor beta chain which control the affinity and the specificity of the interaction with interleukin-2. AB - The beta chain of the interleukin-2 (IL-2) receptor (IL-2R beta) and the interleukin-3 (IL-3) binding protein AIC2A are members of the family of cytokine receptors, which also includes the receptors for growth hormone (GHR) and prolactin. A four amino acid sequence of AIC2A has recently been shown to be critical for IL-3 binding. We analyze here the function of the analogous sequence of human IL-2R beta and identify three amino acids, Ser132, His133 and Tyr134, which play a critical role in IL-2 binding. We show that some mutant IL-2 proteins with substitutions of a critical Asp residue in the N-terminal alpha helix bind the mutant IL-2R beta receptor with a higher affinity than the wild type receptor. This suggests that the critical Asp34 in the ligand and the sequence Ser-His-Tyr (positions 132-134) in the receptor interact directly. On the double barrel beta-stranded structural model of cytokine receptors, the residues important for ligand binding in IL-2R beta, AIC2A and GHR map to strikingly similar locations within a barrel, with the interesting difference that it is the N-terminal barrel for GHR and the C-terminal barrel for IL-2R beta and AIC2A. PMID- 1600938 TI - A novel extensin that may organize extracellular matrix biogenesis in Volvox carteri. AB - ISG is a sulphated, extracellular glycoprotein synthesized for only a few minutes in inverting Volvox embryos and inverting sperm cell packets. This control operates at the level of transcription. ISG has been characterized by studies of protein chemistry and electron microscopy. The primary structure of ISG has been derived from genomic DNA and cDNA. ISG is composed of a globular and a rod-shaped domain. The rod-shaped domain represents a member of the extensin family with numerous repeats of Ser-(Hyp)4-6 motifs. A synthetic decapeptide matching the C terminal sequence is able to disaggregate the organism into individual cells. Immunofluorescence microscopy localizes ISG within the boundary zone of the ECM. PMID- 1600939 TI - The yeast WBP1 is essential for oligosaccharyl transferase activity in vivo and in vitro. AB - Asparagine-linked N-glycosylation is a highly conserved and functionally important modification of proteins in eukaryotic cells. The central step in this process is a cotranslational transfer of lipid-linked core oligosaccharides to selected Asn-X-Ser/Thr-sequences of nascent polypeptide chains, catalysed by the enzyme N-oligosaccharyl transferase. In this report we show that the essential yeast protein WBP1 (te Heesen et al., 1991) is required for N-oligosaccharyl transferase in vivo and in vitro. Depletion of WBP1 correlates with a defect in transferring core oligosaccharides to carboxypeptidase Y and proteinase A in vivo. In addition, in vitro N-glycosylation of the acceptor peptide Tyr-Asn-Leu Thr-Ser-Val using microsomal membranes from WBP1 depleted cells is reduced as compared with membranes from wild-type cells. We propose that WBP1 is an essential component of the oligosaccharyl transferase in yeast. PMID- 1600940 TI - A novel methyl transferase induced by osmotic stress in the facultative halophyte Mesembryanthemum crystallinum. AB - Molecular mechanisms of osmotic stress tolerance were studied in Mesembryanthemum crystallinum (ice plant), a facultative halophyte capable of adjusting to and surviving in highly saline conditions. We screened a subtracted cDNA library enriched for salt stress-induced mRNAs to identify transcripts involved in this plant's adaptation to salinity. One mRNA, Imt1, was found to be up-regulated in leaves and, transiently, in roots. Nuclear run-on assays indicated that this mRNA is transcriptionally regulated. Imt1 encoded a predicted polypeptide of M(r) 40,250 which exhibited sequence similarity to several hydroxymethyl transferases. Expression of the protein in Escherichia coli and subsequent activity assays identified the protein as a novel myoinositol O-methyl transferase which catalyzes the first step in the biosynthesis of the cyclic sugar alcohol pinitol. Pinitol accumulates in salt-stressed M.crystallinum and is abundant in a number of salt- and drought-tolerant plants. The presence of high levels of sugar alcohols correlates with osmotolerance in a diverse range of organisms, including bacteria, fungi and algae, as well as higher plants. The stress-initiated transcriptional induction of IMT1 expression in a facultative halophyte provides strong support for the importance of sugar alcohols in establishing tolerance to osmotic stress in higher plants. PMID- 1600941 TI - ARD1 and NAT1 proteins form a complex that has N-terminal acetyltransferase activity. AB - Two yeast genes, ARD1 and NAT1, are required for the expression of an N-terminal protein acetyltransferase. This activity is required for full repression of the silent mating type locus HML, for sporulation, and for entry into G0. While the NAT1 gene product is thought to be the catalytic subunit of the enzyme, the role of the ARD1 protein has remained unclear. We have used epitope tagged derivatives of ARD1 and NAT1 to provide biochemical evidence for the formation of an ARD1 NAT1 complex, and to show that both proteins are required for the N-terminal acetyltransferase activity. We also present evidence for the formation of ARD1 ARD1 homodimers. Deletion analysis suggests that the C-terminal region of ARD1 may be involved in the formation of both ARD1-ARD1 and ARD1-NAT1 complexes. PMID- 1600942 TI - Restin: a novel intermediate filament-associated protein highly expressed in the Reed-Sternberg cells of Hodgkin's disease. AB - We have identified a cDNA coding for a protein of 160 kDa which is expressed in in vitro cultured human peripheral blood monocytes. The predicted amino acid sequence contains an alpha-helical rod domain possessing features characteristic of intermediate filament proteins. However, the immunocytochemical staining pattern, abundance and solubility in Triton X-100/high salt buffers suggest that this protein is probably only associated with the intermediate filament network and represents a new type of intermediate filament associated protein. In a survey of normal, inflammatory and human tumour tissue samples, this protein, which we have named restin, was found to be highly expressed in Reed-Sternberg cells, the tumoral cells diagnostic for Hodgkin's disease. We suggest that restin overexpression may be a contributing factor in the progression of Hodgkin's disease. PMID- 1600943 TI - Enhanced binding of a 95 kDa protein to p53 in cells undergoing p53-mediated growth arrest. AB - To explore the biochemical functions of p53, we have initiated a search for cellular p53-binding proteins. Coprecipitation of three polypeptides was observed when cell lines overexpressing a temperature-sensitive (ts) p53 mutant were maintained at 32.5 degrees C (wild-type p53 activity, leading to growth arrest) but not at 37.5 degrees C (mutant p53 activity). One of these three proteins, designated p95 on the basis of its apparent molecular mass, was highly abundant in p53 immune complexes. We demonstrate herein that p95 is a p53-binding protein, which exhibits poor p53-binding in cells overproducing several distinct mutant p53 proteins. Yet, p95 associates equally well with both the wild-type (wt) and the mutant conformations of the ts p53 in transformed cells growth-arrested at 32.5 degrees C. On the basis of our findings we suggest that wt p53 activity increases p53-p95 complex formation and that such interaction may play a central role in p53 mediated tumour suppression. PMID- 1600944 TI - Dual functions of CDC6: a yeast protein required for DNA replication also inhibits nuclear division. AB - The Saccharomyces cerevisiae gene CDC6, whose protein product is required for DNA replication, is transcribed only in late G1 and S phases. We have discovered a critical reason why CDC6 expression is regulated in this fashion. Constitutive CDC6 transcription greatly delayed the initiation of M phase without effecting the G1-S transition or growth rate. This occurred in both fission and budding yeasts. The CDC6-induced M phase delay was dependent on the wee1/mik1 mitotic inhibitor kinases and was greatly accentuated in strains defective for the cdc25/MIH1 mitotic inducer phosphatases, indicating that CDC6 indirectly inhibits activation of the p34cdc2/CDC28 M phase kinase. Thus CDC6 appears to have an important and perhaps unique dual role in S phase, it is first required for the initiation of DNA replication and then actively participates in the suppression of nuclear division. PMID- 1600945 TI - Identification of a non-basic domain in the histone H4 N-terminus required for repression of the yeast silent mating loci. AB - We have shown previously that a stretch of four charged residues (16-19) at the histone H4 N-terminus is involved in repression of the yeast silent mating loci. One of these residues, Lys16, is a site for acetylation, which may prevent repression of the silent mating loci. In this paper we ask whether other sequences in histone H4, possibly in conjunction with H3 residues, are required for repression. We find that even in combination, the other seven acetylatable lysines in H3 and H4 do not function in repression. In contrast, we have found that an adjacent relatively uncharged domain (residues 21-29) is required for repression and that single amino acid insertions and deletions in this region are extremely detrimental. We propose that the basic and non-basic domains together form a DNA (or protein) induced amphipathic alpha-helix required in the formation of a repressive chromatin structure. PMID- 1600946 TI - The nucleolar transcription factor mUBF is phosphorylated by casein kinase II in the C-terminal hyperacidic tail which is essential for transactivation. AB - UBF is a DNA binding protein which interacts with both the promoter and the enhancer of various vertebrate ribosomal RNA genes and functions as a transcription initiation factor for RNA polymerase I (pol I). We have purified murine UBF to apparent molecular homogeneity and demonstrate that its transactivating potential, but not its DNA binding activity, is modulated in response to cell growth. In vivo labelling experiments demonstrate that UBF is a phosphoprotein and that the phosphorylation state is different in growing and quiescent cells. We show that UBF is phosphorylated in vitro by a cellular protein kinase which by several criteria closely resembles casein kinase II (CKII). A major modification involves serine phosphoesterifications in the carboxy terminal hyperacidic tail of UBF. Deletions of this C-terminal domain severely decreases the UBF directed activation of transcription. The data suggest that phosphorylation of UBF by CKII may play an important role in growth dependent control of rRNA synthesis. PMID- 1600948 TI - Gene inactivation of Pf11-1 of Plasmodium falciparum by chromosome breakage and healing: identification of a gametocyte-specific protein with a potential role in gametogenesis. AB - We report the identification of the product of the Plasmodium falciparum Pf11-1 gene and demonstrate that it is a gametocyte-specific protein that has a potential role in the rupture of the host erythrocyte and emergence of the gametes (gametogenesis). The Pf11-1 gene is a large locus (30 kb) whose sequence predicts a glutamic acid-rich polypeptide. Our identification of the Pf11-1 gene product as gametocyte specific was greatly facilitated by the isolation of a mutant parasite clone in which greater than 90% of the Pf11-1 gene was deleted. Molecular analysis of the mutant locus suggests that the underlying genetic mechanism is chromosome breakage and subsequent healing by the addition of telomere repeats. PCR-based analysis showed that similar DNA rearrangements occur commonly in small subpopulations of most laboratory strains, suggesting that the Pf11-1 locus represents a fragile chromosome region. Northern blot analysis demonstrates that a large Pf11-1 gene-specific transcript (much greater than 10 kb) is present in gametocytes but not in asexual blood stage parasites. The Pf11 1 protein was localized by electron microscopy to granules in the cytoplasm of gametocytes adjacent to the membrane of the parasitophorous vacuole. Following in vitro stimulation of gametogenesis, the Pf11-1 protein was found in the membrane of lysed erythrocytes, suggesting a role for Pf11-1 in erythrocyte rupture within the mosquito gut. PMID- 1600949 TI - Light regulatory sequences are located within the 5' portion of the Fed-1 message sequence. AB - We have previously shown that element(s) mediating a light-induced increase in the abundance of Fed-1 mRNA in the leaves of transgenic tobacco plants are located within the transcribed portion of the gene. As part of an effort to define the mechanism of this effect, we report here that cis-acting elements capable of mediating a 5-fold light-induced increase in the abundance of this mRNA are located within a region comprising the 5' leader and first third of the Fed-1 coding sequence. No activity was detected in the 3' untranslated region of the gene. In a gain-of-function assay, the 5' region was found to be capable of conferring light responsiveness on three different reporter sequences, although experiments with the gusA reporter were complicated by an apparent negative light effect on the stability of this mRNA. Deletion experiments show that at least one essential light regulatory element is located in the 5' untranslated region of Fed-1 between nucleotides +19 and +57. Additional Fed-1 sequences, including a portion of the protein coding region, are required to confer positive responsiveness on the gusA reporter. These additional sequences may include specific light regulatory elements or simply provide an environment in which the leader element can function normally. PMID- 1600947 TI - Differential splicing of the GHF1 primary transcript gives rise to two functionally distinct homeodomain proteins. AB - The POU domain protein GHF-1 has a critical role in generation, proliferation and phenotypic expression of three pituitary cell types. GHF-1 functions in part by binding to and transactivating the promoters of both the growth hormone (GH) and prolactin (PRL) genes and that of the GHF1 gene itself. We describe a naturally occurring isoform of GHF-1, GHF-2, in which an additional 26 amino acids are inserted into the activation domain of the protein as a result of alternative splicing. GHF-2 retains the DNA binding activity of GHF-1 and can activate the GH promoter but has lost the ability to activate the PRL and GHF1 promoters. These results suggest that GHF-2 may function in differential target gene activation during differentiation of the somatotrophic lineage. Both GHF-1 and GHF-2 transcripts are specifically expressed in the anterior pituitary. Analysis of the genomic GHF1 gene shows that most of the distinct functional domains of GHF-1 (and GHF-2) are encoded by separate exons. Gene segment duplication and exon shuffling may have contributed to the evolution of this cell type-specific transcriptional regulatory gene. PMID- 1600950 TI - Selective extracellular release of cholera toxin B subunit by Escherichia coli: dissection of Neisseria Iga beta-mediated outer membrane transport. AB - The C-terminal domain (Iga beta) of the Neisseria IgA protease precursor is involved in the transport of covalently attached proteins across the outer membrane of Gram-negative bacteria. We investigated outer membrane transport in Escherichia coli using fusion proteins consisting of an N-terminal signal sequence for inner membrane transport, the Vibrio cholerae toxin B subunit (CtxB) as a passenger and Iga beta. The process probably involves two distinct steps: (i) integration of Iga beta into the outer membrane and (ii) translocation of the passenger across the membrane. The outer membrane integrated part of Iga beta is the C-terminal 30 kDa core, which serves as a translocator for both the passenger and the linking region situated between the passenger and Iga beta core. The completeness of the translocation is demonstrated by the extracellular release of the passenger protein owing to the action of the E. coli outer membrane OmpT protease. Translocation of the CtxB moiety occurs efficiently under conditions preventing intramolecular disulphide bond formation. In contrast, if disulphide bond formation in the periplasm proceeds, then translocation halts after the export of the linking region. In this situation transmembrane intermediates are generated which give rise to characteristic fragments resulting from rapid proteolytic degradation of the periplasmically trapped portion. Based on the identification of translocation intermediates we propose that the polypeptide chain of the passenger passes in a linear fashion across the bacterial outer membrane. PMID- 1600951 TI - Hsp104 is required for tolerance to many forms of stress. AB - Heat-shock proteins (hsps) are induced by many types of stress. In Saccharomyces cerevisiae, a mutation in the HSP104 gene, a member of the highly conserved hsp100 gene family, reduces the ability of log-phase fermenting cells to withstand high temperatures after mild, conditioning pretreatments. Here, we examine the expression of hsp104 and its importance for survival under many different conditions. Hsp104 is expressed at a higher level in respiring cells than in fermenting cells and is required for the unusually high basal thermotolerance of respiring cells. Its expression in stationary phase cells and spores is crucial for the naturally high thermotolerance of these cell types and for their long-term viability at low temperatures. The protein is of critical importance in tolerance to ethanol and of moderate importance in tolerance to sodium arsenite. Thus, the hsp104 mutation establishes the validity of a long standing hypothesis in the heat-shock field, namely, that hsps have broadly protective functions. Further, that a single protein is responsible for tolerance to heat, ethanol, arsenite and long-term storage in the cold indicates that the underlying causes of lethality are similar in an extraordinary variety of circumstances. Finally, the protein is of little or no importance in tolerance to copper and cadmium, suggesting that the lethal lesions produced by these agents are fundamentally different from those produced by heat. PMID- 1600952 TI - Polymerase chain reaction-based comprehensive procedure for the analysis of the mutation spectrum at the hypoxanthine-guanine phosphoribosyltransferase locus in Chinese hamster cells. AB - We have established a comprehensive procedure based on the polymerase chain reaction (PCR) to analyze the molecular spectrum of mutations at the hypoxanthine guanine phosphoribosyltransferase (hprt) locus in Chinese hamster cells. The procedure includes direct sequencing of PCR-amplified hprt cDNA for locating point mutations in the expressed coding sequences, multiplex PCR amplification of the hprt exons for screening large deletions, and direct sequencing of PCR amplified hprt exons and their flanking regions for detecting intronic mutations resulting in mRNA splicing errors. Using this procedure, we have identified different types of mutations among a representative collection of spontaneous and induced HPRT-deficient Chinese hamster cell mutants. This procedure is simple, rapid, accurate, and practical for a comprehensive study of the mutation spectrum in a large number of HPRT-deficient Chinese hamster cell mutants. PMID- 1600953 TI - Factors influencing mutation at the hprt locus in T-lymphocytes: studies in normal women and women with benign and malignant breast masses. AB - A prospective, longitudinal study was performed to test the hypothesis that environmental factors (e.g., diet or cigarette smoking) modulate genetic damage caused by treatment for breast cancer and render these women more susceptible to developing second malignancies. A total of 107 women (49 with breast cancer, 52 with benign breast masses, and 6 normal women) were enrolled. This report describes initial studies at the time of enrollment and disease presentation. Mutant frequency at the hprt locus and cloning efficiency of peripheral blood lymphocytes did not differ significantly among the 3 groups. Mutant frequency increased with age, with a history of cigarette smoking, and with the number of years that current smokers used cigarettes. There was no correlation in women with benign masses between mutant frequency and the incidence of chromosome aberrations (28 women) or sister chromatid exchanges (23 women). A maternal history of breast cancer did not influence mutant frequency. There was no significant relationship between dietary intake of vitamins A, B12, C and E, folacin, selenium, calcium, caffeine, or multivitamin pills, and mutant frequency. Serum folate levels in the deficient range were associated (P = 0.02) with elevated mutant frequencies, whereas SCE rates inversely correlated with serum vitamin B12 levels. These results confirm the importance of age and, less so, cigarette smoking as factors that influence mutant frequency and suggest that a micronutrient, folic acid, may modify genetic damage at the hprt locus. To the extent that somatic mutation contributes to carcinogenesis, these environmental factors may enhance the risk of developing malignant transformation. PMID- 1600954 TI - In vitro mutagenesis of the yeast SUP4-o gene to identify all substitutions that can be detected in vivo with the SUP4-o system. AB - SUP4-o, a suppressor tRNA gene, is the target in a system for characterizing mutational specificity in the yeast Saccharomyces cerevisiae. To date, screening for loss of suppression has detected 172 of the 267 base-pair substitutions possible in the exons and intron of the SUP4-o gene. Although many of the remaining 95 changes might not be detected by this screen, some might occur spontaneously, or be induced, only at very low frequencies. For the purpose of analyzing mutational specificity, it would be valuable to determine which of these substitutions can be detected with the genetic screen employed in this system and which cannot. Thus we used in vitro mutagenesis to generate the 95 substitutions not yet detected in SUP4-o in vivo. Assessment of the phenotypes conferred by these 95 directed mutations revealed that 50 would completely escape detection and only 45 would pass through the first stage of the screen. Of these 45 substitutions, 2 are detectable but have not yet been found among more than 5,000 characterized SUP4-o mutations that arose in vivo. In addition, 4 others should be detected by slightly relaxing the current criteria for selection of SUP4-o mutants. The results indicate that with these modifications the system can detect 174/225 substitutions possible in the SUP4-o exons and 4/42 in the intron. PMID- 1600955 TI - Mutagenesis and DNA repair for alkylation damages in Escherichia coli K-12. AB - In this work we report on the isolation of an Escherichia coli K-12 mutation, which confers a high sensitivity to bacteria cells to mutagenesis by simple monofunctional alkylating agents. The mutation emerged spontaneously from a bacterial strain that already proved useful in various mutagenicity studies. By monitoring the influence of such a mutation on the frequency of induced mutation by ethylating (EMS, DES, ENU, ENNG) vs. methylating (MMS, DMS, MNU, MNNG) compounds, and on the in vivo repair capacity for different alkyl-DNA lesions (O6 alkG, N7-alkG, N3-meA), we conclude that the mutation should affect the gene (ogt) that encodes constitutive DNA repair alkyltransferase (ATase). Thus in the presence of ada, differences in mutagenicity were observed only with ethylating agents; the sensitization of cells to both the ethylating and methylating partners requiring, by contrast, the absence of the ada protein. These results support the reported in vitro substrate specificities for both ogt and ada ATases. The parental cells exhibited biphasic dose-response curves in accordance with the idea of low basal level saturation attributed to the uninducible ogt ATase. Deficient bacterial derivatives showed, by contrast, linear mutation induction responses. The in vivo removal of alkylated bases from DNA was measured in bacterial strains deficient in the excision repair pathway (delta uvrB) and unable to induce the adaptive response (ada::Tn10). The very low initial levels for O6-meG and O6-etG (1.1 and 0.2 molecules per cell, respectively) were readily repaired by the parental cells but remained unchanged in the hypermutable derivatives. This result suggests that in the absence of nucleotide excision repair and of the adaptive response, no alternative pathway, other than ogt, is available for the repair of the major mutagenic lesion, O6-alkG, at least during the first 4 hours after alkylation. Comparatively, no differences were found in the capacity to repair the major lethal adduct, N3-meA, in agreement with the fact that no effect on cell survival was detected. In conclusion, we propose that the biological significance of the ogt protein relies mainly on its ability to prevent mutagenesis by low levels of bulkier ethylation products (especially in the absence of uvr excision repair.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1600956 TI - Isolation by fluorescence-activated cell sorting of cells of a human lymphoblastoid cell strain containing mutations in the lambda immunoglobulin gene. AB - Fluorescence-activated cell sorting (FACS) was used to establish clonal populations of a human lymphoblastoid cell strain that contain spontaneously occurring and N-methyl-N'-nitro-N-nitrosoguanidine-induced mutations in the lambda immunoglobulin gene. Multiple rounds of FACS using a monoclonal antibody specific for the membrane-expressed human lambda immunoglobulin were used to enrich the population fraction of cells lacking a wild-type lambda immunoglobulin on the cell surface. Approximately 20% of the clonal populations established after five rounds of FACS-mediated enrichment did not express the lambda immunoglublin epitope recognized by the monoclonal antibody used for selection. However, evaluation of the FACS-selected mutant clonal populations with a polyclonal antilambda antibody, or a monoclonal antibody directed against a different epitope on the lambda immunoglobulin made by the T5-1 cells, indicated that the mutant clonal populations expressed lambda immunoglobulin on their cell surfaces. Additionally, the presence of lambda mRNA and of both secreted and cytoplasmic lambda protein confirmed the transcription and translation of the lambda immunoglobulin gene. These data suggest that FACS-mediated selection employing epitope-specific monoclonal antibodies provides a powerful technique for isolation of cell populations that express mutations within the coding region of the lambda immunoglobulin gene. PMID- 1600957 TI - Structure-activity relationship in the mutagenic effect of chiral or racemic 2 bromo-propanamides on Salmonella typhimurium. AB - Some 2-bromo-propanamides were prepared and tested for direct mutagenicity in Salmonella typhimurium TA 100. Results confirm the mutagenic activity of 2-bromo N-benzyl-propanamide and indicate that it is independent of enantiomeric configuration. A variation in the chemical structure, namely, the addition of a methyl group at the benzylic carbon, causes the four resulting diastereomers to be devoid of any activity. Conversely, some racemic ring-substituted methoxy and/or hydroxy derivatives of the parent compound displayed mutagenic properties, causing an increase in the number of his+ revertants up to 524 per milligram per plate. PMID- 1600958 TI - Some characteristics of oogenesis in the female Turkish hamster subjected to modified environments. AB - The hibernating female Turkish hamster (Mesocricetus brandti) was utilized for a study of possible in vivo effects of cold on oocyte maturation. Such a physiologic model offered an opportunity to analyze the ability of oocytes exposed to prolonged periods of reduced core temperature and/or light to subsequently mature to Metaphase II. Detailed observations of core temperatures, torpor/arousal, serum estradiol, and ovarian histology were made. An average incidence of 37.7% binuclearity was found in the germinal vesicle, metaphase I and II occytes of this species. Maturation to Metaphase II of total chromosome complements did not vary significantly in the experimental groups compared with the control, but aneuploidy was detected in the oocytes of animals exposed to reduced temperature or light. An effect of in vivo reduced core temperatures on oocyte chromosome complements validates many of the published in vitro studies with temperature reduction. The model presents an excellent physiologic system for perturbing and analyzing many aspects of mammalian oocyte development. PMID- 1600960 TI - Sister chromatid exchanges in chick embryos after treatment with the phenoxy herbicide MCPA. AB - The phenoxyherbicide and peroxisome proliferator 2-methyl-4-chlorophenoxyacetic acid (MCPA) was tested for its ability to induce sister-chromatid exchanges (SCE) in chick embryos. Erbitox E30 (a commercial formulation containing 28% MCPA sodium potassium salt as active ingredient) was injected into the air chamber in concentrations of MCPA of 0, 0.35, 0.7, 1.4, 2.8, or 5.6 mg/egg on day 0 of incubation. Pure MCPA sodium salt was tested at 2.8 mg/egg. Neutral red at 0.25 mg/egg was the mutagenic reference compound (positive control group). Eggs were then incubated for 4 days. MCPA induced a slight but significant increase in SCE frequency (about 1.3 times base line) at 2.8 mg/egg. The dose of 5.6 mg/egg was toxic. No difference in genetic activity between the commercial formulation and the pure compound was found. A cell cycle delaying effect of MCPA was evident at all the dose levels tested. The mitotic index remained unchanged. PMID- 1600959 TI - Clastogenic effect of fenfluramine in mice bone marrow cells in vivo. AB - Fenfluramine, an amphetamine derivative used in the treatment of obesity, has been evaluated in vivo in the bone marrow cells of Swiss albino mice using two cytogenetic endpoints for assessing its genotoxic and clastogenic potentials. Concentrations of 0.75, 1.5, 3.0, and 5.0 mg/kg b.w. were administered orally for the study of sister chromatid exchange frequencies and chromosome aberrations (CA). SCE frequencies showed a positive dose response; 1.5 mg/kg being the minimum effective concentration. Fen caused a prolongation of cell cycle at all concentrations. Except for the minimum therapeutic dose (0.75 mg), all other doses (1.5, 3.0, and 5.0 mg) showed a significant increase in the percentage of damaged cells over that of the vehicle control. The degree of clastogenicity was directly proportional to the dosage used and inversely related with the duration of treatment. A gradual reduction of the clastogenic potential was observed after 12 and 24 hr of exposure, indicating that the maximum effect occurs at the middle or late synthetic phase of the cell cycle. This study, probably the first detailed screening of the drug for its genotoxicity, shows that Fen is moderately clastogenic and a DNA damaging agent in vivo. PMID- 1600961 TI - Ozone is mutagenic in Salmonella. AB - Ozone is a highly reactive gas that has been tested for genotoxicity in a number of systems. Induced genetic damage resulting from ozone treatment may not be readily observed because of the high toxicity of the chemical and difficulties in generating and administering controlled concentrations. The mutagenicity of ozone was investigated in Salmonella typhimurium using a plate test protocol designed for reactive vapours and gases. Ozone, at two to three consecutive doses, induced weak, albeit statistically significant, mutagenic responses in tester strain TA102 with and without Aroclor-induced rat liver S9 (lowest effective mean concentration of 0.019 ppm; 35 min total exposure). However, dose-related responses were not always obtained. No mutagenicity was detected in strains TA98, TA100, or TA1535, with or without S9. In strain TA104, ozone induced a weak response only at a single dose with S9; this response was not reproducible. Mutagenicity was dependent on the ozone flow rate and total exposure time, with variations in the optimum dose-time regimen leading to toxicity or complete inactivity. The data show that ozone is a very weak bacterial mutagen and only when tested under narrowly prescribed, subtoxic dosing conditions. PMID- 1600963 TI - Perioperative experience with amrinone. AB - Amrinone is the only phosphodiesterase fraction III inhibitor currently available in the USA for the treatment of perioperative biventricular failure. Patients with chronic congestive heart failure (CHF) show down-regulation of the beta 1 adrenergic receptor with a decrease in receptor density and altered responses to catecholamines. Intravenous administration of amrinone can transiently restore beta 1-adrenergic responses in patients who have CHF. Amrinone's mechanism of vasodilatation, independent of the beta 1-adrenergic receptor, nitrates, and calcium entry blockers, proves an important therapeutic option for pulmonary hypertension. The elimination half-life of amrinone in volunteers is 2.6-4.1 h, and 3.5 h when administered into the cardiopulmonary bypass (CPB) circuit. Different loading and infusion doses have been reported for amrinone. Investigators have demonstrated that increases in cardiac output following amrinone administration are directly related to plasma concentration. In cardiac surgical patients, following a dose of 0.75 mg kg-1 administered into the CPB circuit, plasma concentrations are subtherapeutic after 10 min. We believe that, when using amrinone to facilitate separation from CPB, a bolus dose of 1.5 mg kg 1 or more should be administered. If therapeutic levels need to be maintained in patients with biventricular failure, an infusion should also be administered after the bolus dose. Additive effects have been demonstrated when catecholamines are administered concomitantly with amrinone and other PDE III inhibitors to increase cyclic AMP in cardiac muscle and improve contractility. The use of amrinone with catecholamines is also important clinically, because together they attenuate the vasoconstrictive effects of catecholamines alone, while the catecholamines support perfusion pressure. Amrinone represents a novel drug for managing biventricular dysfunction in cardiac surgical patients. PMID- 1600962 TI - Mutagenicity of beta-alkyl substituted acrolein congeners in the Salmonella typhimurium strain TA100 and genotoxicity testing in the SOS chromotest. AB - The beta-alkyl substituted acrolein congeners crotonaldehyde, trans-2-pentenal, trans-2-hexenal, 2,4-hexadienal, and trans-2-heptenal were clearly mutagenic in a slightly modified preincubation Ames test with Salmonella typhimurium TA100 with and without S9 mix using a threefold bacterial cell density and a 90-min preincubation time, whereas trans-cis-2,6-nonadienal did not show any mutagenic activity. The greatest impediment to adequate mutagenicity testing of these compounds is their toxicity toward bacteria. Within the congener family tested, toxicity increases as a function of both chain length and lipophilicity, and it becomes more and more difficult to demonstrate mutagenicity. Mutagenicity decreases with increasing chain length. This effect may be explained by increasing toxicity. The effect of S9 mix seems to be mostly nonenzymatic detoxication by nonspecific scavanger protection of bacterial cytotoxicity. No indication could be found that bioactivation plays a role in S9-mediated reduction of bacterial cytotoxicity. Although positive mutagenic outcomes could be obtained with the SOS chromotest for other alpha, beta-unsaturated carbonyl compounds, these acrolein congeners were not genotoxic in this test, most probably because they are toxic for the Escherichia coli bacteria PQ37 and PQ243. PMID- 1600964 TI - Milrinone in the treatment of low output states following cardiac surgery. AB - Milrinone is known to have beneficial haemodynamic and clinical effects in patients with congestive heart failure. An investigation into the safety and efficacy of milrinone in patients following heart surgery was undertaken by the European Milrinone Multicentre Trial Group. This paper reports the efficacy, the effects on left heart function, and the adverse events in the study. Ninety-nine adult patients, 61 coronary artery bypass grafting (CABG), 33 valve surgery (VS), and five CABG+VS were studied. Three dosage regimens were investigated sequentially. All patients received a loading dose of intravenous milrinone 50 micrograms kg-1 over 10 min, followed by an infusion of either 0.375 micrograms kg-1 min-1, 0.5 microgram kg-1 min-1, or 0.75 microgram kg-1 min-1 over 12 h. The groups were comparable for age, weight, and surface area; however, in the group receiving 0.5 microgram kg-1 min-1 there were more females and patients undergoing mitral valve surgery. Efficacy criteria of an increase in cardiac index of 30% and/or a decrease in mean pulmonary capillary wedge pressure of 25% were fulfilled by 77 patients at the 60-min measurement. Of the remaining 22 patients, 17 were clinically satisfactory and fulfilled efficacy criteria at some time during the study. At 15 min and 60 min there was a dose-related decrease in systolic and diastolic arterial pressure; however, there was no significant difference in the mean arterial pressure measurements. In all groups there was an improvement in cardiac index at 15 min following the start of milrinone, which was sustained during and up to 4 h after the infusion. This was closely associated with changes in stroke volume index and systemic vascular resistance, and not solely due to a change in heart rate. PMID- 1600965 TI - Milrinone and the pulmonary vascular system. AB - In a multicentre study of 99 adult patients undergoing cardiac surgery, if post operative cardiac failure was demonstrated (pulmonary capillary wedge pressure greater than 8 mmHg, cardiac index less than 2.5 litre min-1 m-2), then a bolus dose of milrinone (50 micrograms kg-1) was given, followed by an infusion at one of three rates (0.375, 0.5 or 0.75 microgram kg-1 min-1), and haemodynamic effects were assessed. Mean pulmonary artery pressures fell by 15% initially (P less than 0.001), and this significant reduction was maintained throughout the infusion period and reversed with the withdrawal of milrinone. Mean pulmonary vascular resistance fell progressively throughout the infusion period, the maximum change (30-40%) being evident at the 12 h point (P less than 0.05). Reversal of this effect after terminating the milrinone infusion was less marked than with pulmonary capillary wedge pressure or mean pulmonary artery pressure. A group of 39 of these patients from two centres were retrospectively divided into three groups: 1. Mitral valve replacement with high baseline pulmonary vascular resistance (greater than 200 dyne s cm-5) 2. Coronary revascularization with lower baseline pulmonary vascular resistance (100-200 dyne s cm-5) 3. Coronary revascularization with high baseline pulmonary vascular resistance (greater than 200 dyne s cm-5). There was a significant reduction in pulmonary vascular resistance and increase in cardiac index in all patients. At the 15 min point, there was significant between-group variation, the fall in pulmonary vascular resistance and increase in cardiac index being greater in Group 1 than in Groups 2 or 3. This difference between groups was not maintained during the infusion. PMID- 1600966 TI - Pathophysiology of the perioperative low output syndrome. AB - Surgery in high-risk cardiac patients is now possible due to improvements in medical techniques. These patients are, however, more likely to develop a low cardiac output syndrome in the perioperative period. The condition may be precipitated by surgery, especially in those with underlying ischaemic heart disease, the initial cardiac insult being followed by diminished contractility and compensatory changes in perfusion pressures due to the release of endogenous catecholamines. Catecholamine release induces myocardial irritability and there is a subsequent increase in heart rate and decrease in cardiac output. As a result, contractility may decrease even further, and the downward spiral worsens. This article reviews current progress in the understanding of the pathophysiology of the low cardiac output syndrome with reference to the various parameters used to assess cardiac function, and the effects of drug therapy on these parameters. PMID- 1600967 TI - Haemodynamic and biological effects of intravenous milrinone in patients with a low cardiac output syndrome following cardiac surgery: multicentre study. AB - The haemodynamic and biological effects of intravenous milrinone were studied in 24 adult patients with a low cardiac output syndrome following cardiac surgery. The patients received a milrinone bolus of 50 micrograms kg-1 over 10 min followed by a 0.375-0.750 micrograms kg-1 min-1 infusion over 48 h. After the first hour of treatment, an increase in cardiac index, systolic index and left ventricular stroke work index, and a decrease in right and left loading pressures, pulmonary artery pressure, systemic vascular resistance and pulmonary vascular resistance were observed while heart rate and systemic arterial pressure were not modified. These haemodynamic effects were maintained over the 48 h of treatment and persisted 3 h after discontinuation of treatment. Milrinone, which possesses inotropic and vasodilatory effects, increased cardiac performance and corrected the low cardiac output in all patients. PMID- 1600968 TI - Overview of the effects of intravenous milrinone in acute heart failure following surgery. AB - We have reviewed the current data evaluating the effects of intravenous milrinone in patients following cardiac surgery. Milrinone has been shown to be effective in the treatment of acute low output syndrome, and a loading bolus infusion of 50 micrograms kg-1 over 10 min causes an increase in cardiac index and a fall in pulmonary capillary wedge pressure. These effects are easily maintained by a continuous infusion regimen. Other haemodynamic effects are seen, including systemic and pulmonary vasodilatation and an increase in heart rate. These effects are not confined to one patient group, but the increase in cardiac index does appear to be more pronounced in those patients with poor haemodynamics prior to treatment. There is a low incidence of adverse events including arrhythmias and hypotension. Thus milrinone appears to be well tolerated in a broad group of adult patients recovering from cardiac surgery. PMID- 1600969 TI - Pharmacology of bipyridine phosphodiesterase III inhibitors. AB - The bipyridine phosphodiesterase III inhibitors amrinone and milrinone form a new class of positive inotropic vasodilator agents that are beneficial in the treatment of acute and chronic heart failure. These agents inhibit the intracellular hydrolysis of cyclic AMP, thereby promoting cyclic AMP-catalysed phosphorylation of sarcolemmal calcium channels and activating the calcium pump. They also have vasodilator and lusitropic actions and are devoid of the central stimulant actions that narrow the therapeutic index of theophylline and other methylxanthines. Receptor down-regulation, which curtails the inotropic efficacy of beta-adrenoceptor agonists, does not compromise the efficacy of phosphodiesterase inhibitors. The effectiveness of these new agents is, however, dependent upon some degree of basal adenylate cyclase activity. PMID- 1600970 TI - Inhalational agents--an update. PMID- 1600971 TI - Maintenance of anaesthesia with propofol--a comparative study of a stepdown infusion of propofol and a low dose infusion supplemented by incremental doses. AB - Forty-four patients, ASA Grade I or II, had anaesthesia induced with propofol at 100 mg min-1 followed by a maintenance rate of 6 mg kg-1 h-1 or a stepdown regimen of 10 mg kg-1 h-1 for 10 min, 8 mg kg-1 h-1 for the next 10 min and at 6 mg kg-1 h-1 thereafter. Anaesthesia was maintained with propofol infused using an Ohmeda 9000 pump supplemented by nitrous oxide and oxygen (2:1) in a Bain circuit with spontaneous ventilation. Incremental doses of 20 mg of propofol were given to both groups as clinically indicated to maintain anaesthesia. Both methods provided satisfactory maintenance of anaesthesia but significantly more incremental doses were required in the group receiving the steady rate infusion. However, a lower cumulative dose was required up to 30 min in this group but not by 40 min. A comparable fall in systolic and diastolic blood pressure and heart rate was seen in both groups. There was no difference in the recovery times between the groups and the total dose did not correlate with time to recovery. PMID- 1600972 TI - Effect of pre-operative metoprolol on cardiovascular and catecholamine response and bleeding during hysterectomy. AB - The effect of a pre-operative dose of metoprolol on the catecholamine and cardiovascular responses to tracheal intubation and surgery, cardiac complications and intra-operative blood loss, were studied in patients undergoing elective hysterectomy during general anaesthesia. The study was double-blind and placebo controlled. The patients received metoprolol 100 mg or placebo orally 1 25 h before anaesthesia. In patients given metoprolol, heart rate and mean arterial pressure were lower during the first 45 min of anaesthesia. Plasma adrenaline and noradrenaline concentrations increased in both groups in response to tracheal intubation and surgery, but were higher after metoprolol. The incidence of arrhythmias was less after metoprolol. The mean operative blood loss was greater in the placebo group (486 +/- 170 ml (SEM) compared to 231 +/- 43 ml (SEM) after metoprolol). We conclude that oral premedication with metoprolol attenuates the hypertensive response to tracheal intubation and reduces both arrhythmias and operative blood loss. PMID- 1600973 TI - The influence of tourniquet ischaemia on post-operative degranulation of polymorphonuclear granulocytes. AB - Degranulation of polymorphonuclear granulocytes following minor surgery and the contributory role of temporary tissue ischaemia in a limb were examined in 22 otherwise healthy patients undergoing elective arthroscopy under general anaesthesia with and without tourniquet. Apart from an increase in lactate levels following tourniquet release there was no difference in complement split product C3d, cortisol, leukocyte or creatinine kinase levels between the two groups. There was a post-operative increase in the plasma E alpha 1-proteinase inhibitor concentration, whereas lactoferrin values decreased 4 h following tourniquet deflation. Anaesthesia and minor surgery are followed by post-operative release of polymorphonuclear neutrophil elastase. This release is not related to complement activation and is apparently unaffected by 50 min of lower limb ischaemia. Anaesthesia and minor surgery do not cause lactoferrin release. PMID- 1600974 TI - Functional and metabolic effects of mexiletine in the rat heart-lung preparation. AB - The effects of mexiletine on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Mexiletine 1, 2, 4 or 8 micrograms ml-1 was administered 5 min after the start of perfusion. Heart rate decreased in the 2, 4 and 8 micrograms ml-1 groups significantly following the drug administration. The highest dose of mexiletine reduced cardiac output significantly, and this dose was associated with a higher incidence of dysrhythmias than the other groups. Although there was no significant difference in myocardial glycogen concentration among groups, ATP contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly less than in the control group. Lactate contents in the 4 micrograms ml-1 and 8 micrograms ml-1 groups were significantly higher than in the control group. Generally, the therapeutic plasma concentration of mexiletine is 0.5-2.0 micrograms ml-1. These results suggest that mexiletine may have a lesser margin of safety than lignocaine. PMID- 1600975 TI - Brachial plexus block using the transcoracobrachial approach. PMID- 1600976 TI - Recommended guidelines for uniform reporting of data from out-of-hospital cardiac arrest: the 'Utstein style'. European Resuscitation Council, American Heart Association, Heart and Stroke Foundation of Canada and Australian Resuscitation Council. PMID- 1600977 TI - Some ethical problems in medicine and cardiology. PMID- 1600978 TI - Influence of social support on cardiac event rate in men with ischaemic type ST segment depression during ambulatory 24-h long-term ECG recording. The prospective population study 'Men born in 1914', Malmo, Sweden. AB - Three-hundred and ninety-four 68-year-old men, representing 60.3% of a cohort of men born in 1914, were examined with ambulatory ECG during 24 h in 1982-83. Ninety-eight (24.8%) men had one or more episodes of ischaemic type ST segment depression (greater than or equal to 0.10 mV), 79 of whom had no history of previous ischaemic heart disease (IHD). During 63 months follow-up, 17 of the 98 suffered a cardiac event, i.e. fatal or non-fatal myocardial infarction (MI) or death due to chronic IHD. The objective of this study was to assess the influence of psychosocial factors, such as social network and social support, on cardiac event rate in men with ischaemic ST segment depression. A higher risk was found among men with little material and informational support (i.e. access to practical services and material resources and access to guidance, advice and information (crude relative risk 4.8; 95% CI; 1.6-14.8) and men with low availability of emotional support (i.e. opportunity for care, encouragement of personal value and feelings of confidence and trust) (crude relative risk 4.3; 95% CI: 1.4-13.3). This association was independent of history of IHD and other known risk factors for myocardial infarction (MI). PMID- 1600979 TI - Tobacco, physical exercise and lipid profile. AB - A group of 572 young cadets from the General Military Academy in Zaragoza (AGEMZA) with a mean age of 19.9 years was studied in two different situations: on admission to the AGEMZA, when physical activity was very intensive (A) and after 8 months, by which time they had all received identical diets and physical activity was considerably reduced (B). On both occasions they were asked about their smoking habits and their personal and family histories. Their height and weight were recorded and a sample of venous blood was taken to determine the lipid, biochemical and haematological profiles. We found that more smokers had a family history of sudden death or acute myocardial infarction than the non smokers. The smokers also showed a lower HDL cholesterol level (54.3 +/- 9.8 mg.dl-1 +/- SD) than the non-smokers (59.4 +/- 10.9) (P less than 0.0001) and a higher level of triglycerides (75.4 +/- 24.7 mg.dl-1) than the non-smokers (65.4 +/- 21.1 mg.dl-1). The smokers had a higher white cell count (8194 +/- 1981 vs 7332 +/- 1672 cells. 10mm-3) (P less than 0.001), a higher haemoglobin value (14.9 +/- 0.9 vs 14.6 +/- 0.9 g.dl-1) (P less than 0.004) and a higher haematocrit value (44.2 +/- 2.3 vs 43.6 +/- 2.7%) (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600980 TI - Clinical relevance of vegetation localization by transoesophageal echocardiography in infective endocarditis. AB - Infective endocarditis is associated with significant morbidity and mortality, with valvular destruction and congestive heart failure being more common in patients with echocardiographically discernible vegetations. The transoesophageal approach affords consistently high quality images with excellent structural resolution. Two-hundred and eighty-one patients with clinically suspected infective endocarditis were studied, to evaluate the prognostic value of ascertaining the site of vegetations. Among them were 118 patients with vegetations attached to the aortic or mitral valve. These patients were followed for a mean period of 14 months. Mitral valve vegetations were associated with a significantly higher incidence of embolic events than vegetations on aortic valves (25% vs 9.7%). The incidence of abscess formation was higher in aortic than in mitral valve endocarditis (6% vs 0%), as were the need for surgical intervention (11% vs 5.5%) and mortality (1.6% vs 0%) respectively). Bivalvular endocarditis was associated with an increased rate of complications: embolism (50%), abscess formation (15%), surgery (35%) and mortality (10%). By multivariate analysis, echocardiographically accessible risk factors for subsequent embolism were a vegetation size of more than 10 mm and mitral valve involvement. Risk factors associated with in-hospital fatality were embolism, a vegetation size of more than 10 mm, and Staphylococcus aureus infection. Our data suggest that the site influences both the rate and the type of complications. Precise echocardiographic visualization of vegetations helps to stratify patients into a high-risk sub-group, perhaps warranting early prophylactic surgical intervention. Transoesophageal echocardiography may play an important role in assessing the clinical outcome for these patients. PMID- 1600981 TI - Detection of sinus venosus atrial septal defect by two-dimensional echocardiography. AB - In a 4-year period, 10 patients (mean age, 3.6 years) with a superior type sinus venosus atrial septal defect were investigated by two-dimensional echocardiography. The defects were easily visualized in all patients using a long axis vena cava superior-inferior plane with a subcostal approach, while the atrial septum seemed to be intact in the coronal plane conventionally used for atrial septal defects of the primum or secundum type. Additional colour flow mapping, performed in two patients, demonstrated shunting across the depicted defect. In our experience, the modified plane is of great diagnostic value in cases with a sinus venosus defect. PMID- 1600982 TI - Characterization and long-term prognosis of patients with effort-induced silent myocardial ischaemia. AB - The aim of this study was to evaluate the anatomo-clinical correlations and the prognostic significance of silent myocardial ischaemia (SI) during exercise testing (ET). Four hundred and six patients with angiographically proven CAD and positive ET were studied. Patients were divided into two groups: 309 patients (Group A) with positive ET for both electrocardiographical findings and angina, and 97 patients (Group B) with positive ET for electrocardiographical findings but not for angina (SI). In Group A the following clinical characteristics differed significantly from Group B: incidence of diabetes mellitus (15.8% vs 27.8%, P less than 0.04); duration of disease (less than 1 month from its first manifestation) (30.4% vs 54.6%, P less than 0.001) and a positive ET at low work load (41.7% vs 50.5%, P less than 0.05). Mortality during follow-up (mean 72 +/- 11 months) was 8.6% in Group A and 8.2% in Group B (NS). Incidence of sudden death was similar in the two groups (2.9% vs 2.06%; NS). The multivariate analysis shown as independent variables, related significantly with a poor prognosis in both groups: left ventricular function (P less than 0.0001); prior myocardial infarction (P less than 0.0001); and multivessel disease (P less than 0.001). In conclusion, patients with a recent onset of symptoms, a positive ET at low workload and diabetes mellitus are more likely to present SI during ET. The long-term prognosis and the incidence of sudden death are similar in patients with painful and painless myocardial ischaemia during ET. PMID- 1600983 TI - The effect of atrio-ventricular delay programming in patients with DDDR pacemakers. AB - Modern DDDR (dual chamber universal, rate responsive) pacemakers are complex, hugely capable devices incorporating new features that theoretically should enhance haemodynamics and therefore quality of life. Ten patients (mean age 48 years) with chronotropic incompetence and high grade A-V block had activity sensing DDDR devices implanted and underwent a randomized double-blind crossover assessment of rate responsive and different fixed atrio-ventricular delay (AVD) settings during 2 weeks of out-of-hospital activity in DDDR mode. Subjective assessment showed improved 'general wellbeing' and preference for 175 ms rate responsive AVD (P less than 0.01) or 125 ms fixed AVD (P less than 0.05). The longest fixed AVD setting (250 ms) was least acceptable and had increased symptom prevalence (P less than 0.02). Perceived exercise capacity and exercise treadmill tolerance was not significantly different at any setting in DDDR mode but was less in DDD mode. Echocardiographically derived stroke distance was greater at 125 ms AVD than 250 ms at 100 b.min-1 (P less than 0.05) but did not differ at slower heart rates at any AVD. Colour Doppler assessed mitral and tricuspid regurgitation was greatest at 250 ms AVD at all heart rates but did not correlate with increased symptomatology. Stroke distance evaluated from the mitral inflow velocity profile allows improved AVD programming during DDDR pacing. Rate adaptive A-V delay is a useful feature during DDDR pacing. PMID- 1600984 TI - Lack of prognostic implications of spontaneously occurring or stimulation induced atrial tachyarrhythmias in patients with dilated cardiomyopathy. AB - A prospective study was undertaken in 102 patients with idiopathic dilated cardiomyopathy to assess the significance of spontaneous and inducible atrial tachyarrhythmias (ATA). Twenty-six patients were in chronic atrial fibrillation (group I) and 76 patients were in sinus rhythm (group II); 14 patients in group II had a clinical history of ATA or episodes of ATA during Holter monitoring. An electrophysiological study was systematically performed. Programmed atrial stimulation was carried out in group II, and used up to two atrial premature stimuli from the right atrium at 2 cycle lengths (sinus cycle length--10%, 600 ms) and then one atrial extrastimulus under infusion of 1 to 4 micrograms. min-1 of isoproterenol. Programmed ventricular stimulation was performed in groups I and II. Sustained atrial tachyarrhythmia (ATA) was induced in 33 patients in group II (42%); isoproterenol infusion facilitated the induction of ATA in only one other patient, who had exercise-related ATA. Eleven patients in group II with spontaneous ATA had inducible sustained ATA. The sensitivity of programmed atrial stimulation to reproduce an ATA was 78.5% and its specificity 64.5%. Inducible ATA was related to a shorter atrial effective refractory period (209 +/- 25 ms vs 228 +/- 32, P less than 0.02). Inducible and spontaneous ATAs were related to older age but not to the existence of spontaneous or inducible ventricular tachycardia; they did not have prognostic significance: the left ventricular ejection fraction and the prognosis were similar in patients with spontaneous or inducible ATA and those without ATA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600985 TI - Difficulties in the use of electrocardiographic criteria for the differential diagnosis of left bundle branch block pattern tachycardia in patients with a structurally normal heart. AB - In patients with left bundle branch block pattern tachycardia, electrocardiographic criteria, based on leads V1, V2 and V6, have been shown to be effective for the diagnosis of ventricular tachycardia in patients with a previous myocardial infarct. To test these criteria on a wider population, we studied 53 consecutive patients with left bundle branch block pattern tachycardia. Seventeen patients had supraventricular tachycardia and 36 had ventricular tachycardia, 18 with a previous myocardial infarction, two with cardiomyopathy, and 16 with a normal heart. The sensitivity for the diagnosis of ventricular tachycardia in patients with a previous myocardial infarct of the combined criteria was 100% but was only 50% for the other patients, which was not significantly different from the patients with supraventricular tachycardia (29%). Two other criteria, right axis shift in tachycardia and ventricular ectopics during sinus rhythm with the same morphology as the tachycardia, were only seen in patients with ventricular tachycardia, and combined with the other criteria allowed the correct identification of 35/36 patients with ventricular tachycardia. To conclude, the electrocardiographic criteria based on leads V1, V2 and V6 are not sensitive for the diagnosis of a ventricular origin of left bundle branch block pattern tachycardia in patients with a normal heart and additional criteria are required for the diagnosis in these patients. PMID- 1600986 TI - Thrombolysis significantly reduces transient myocardial ischaemia following first acute myocardial infarction. AB - In order to investigate whether thrombolysis affects residual myocardial ischaemia, we prospectively performed a predischarge maximal exercise test and early out-of-hospital ambulatory ST segment monitoring in 123 consecutive men surviving a first acute myocardial infarction (AMI). Seventy-four patients fulfilled our criteria for thrombolysis, but only the last 35 patients included received thrombolytic therapy. As thrombolysis was not available in our Department at the start of the study, the first 39 patients included were conservatively treated (controls). No significant differences in baseline clinical characteristics were found between the two groups. In-hospital atrial fibrillation and digoxin therapy was more prevalent in controls (P less than 0.05). During exercise, thrombolysed patients reached a higher maximal work capacity compared with controls: 160 +/- 41 vs 139 +/- 34 W (P less than 0.02). Thrombolysis resulted in a non-significant reduction in exercise-induced ST segment depression: prevalence 43% vs 62% in controls. However, during ambulatory monitoring the duration of transient myocardial ischaemia was significantly reduced in thrombolysed patients: 322 min vs 1144 min in controls (P less than 0.05). Thrombolysed patients reached a higher heart rate during transient ischaemic episodes: 114 +/- 17 vs 93 +/- 11 b.min-1 in controls (P less than 0.001). In conclusion, thrombolytic therapy administered for a first AMI significantly reduces the burden of transient myocardial ischaemia. This may explain the improvement in myocardial function during physical activities, which was also observed in this study. PMID- 1600987 TI - Evaluation of left-to-right shunts in adults with atrial septal defect using first-pass radionuclide cardiography. AB - Non-invasive determination of left-to-right shunts at the atrial level was performed by a new procedure using first-pass radionuclide measurement of cardiac output of the right and left ventricle. In 23 patients with coronary artery disease without shunt the mean difference between the cardiac outputs of the right and left ventricle was 0.04 l.min-1, the limits of agreement -0.80 to 0.88 l.min-1 and the 95% confidence interval for the bias -0.14 to 0.22 l.min-1. Right sided cardiac catheterization was performed to assess the severity of the arterio venous shunt by oximetry in 18 adult patients with atrial septal defects. The range of pulmonary-to-systemic flow ratios was 1.4 to 5.0 (mean 2.7) by oximetry and 1.3 to 4.4 (mean 2.5) by the radionuclide technique. The mean difference between flow ratios measured by the two methods was 0.25, the limits of agreement, -0.85 to 1.35 and the 95% confidence intervals for the bias -0.02 to 0.52. In two patients the difference in flow ratios was more than 1. In one of these the oximetric value was more than 2, and the radionuclide value less than 2. The limits of agreement between flow ratios determined by repeated measurements were -1.05 to 0.97, and by two independent observers -0.75 to 0.77. The present findings suggest that first-pass radionuclide determination of left to-right shunts through atrial septal defects is both reproducible and accurate when compared to the oximetric technique. PMID- 1600988 TI - Residual atrial septal defects following balloon mitral valvuloplasty using different techniques. A transthoracic and transoesophageal echocardiography study demonstrating an advantage of the Inoue balloon. AB - The incidence and severity of atrial septal defects following balloon mitral valvuloplasty have been assessed using transthoracic and transoesophageal echocardiography in 20 patients 3-36 months following the procedure. In eight patients (group A) the atrial septum was dilated with an 8 mm Olbert balloon and either a double or bifoil balloon used to dilate the mitral valve. In 12 patients (group B) the Inoue balloon, with a slimmer deflated profile, was used following dilatation of the interatrial septum with a 14 French vessel dilator. In group A, using transthoracic echocardiography, one atrial septal defect was imaged and transatrial flow detected by colour flow Doppler in five patients. In seven of the eight patients transoesophageal echocardiography clearly imaged an atrial septal defect and left-to-right shunting was demonstrated by colour flow Doppler. Valsalva contrast studies revealed residual transatrial flow in all eight patients. The mean width of the colour flow jet was 5.8 mm. In group B patients, using transthoracic echocardiography, only one patient had evidence of residual transatrial flow (demonstrated by Valsalva contrast). Using transoesophageal echocardiography Valsalva contrast studies, transatrial flow was seen in 11 of the 12 patients. However, no defects were imaged and colour flow Doppler indicated left-to-right shunting in only two patients. The mean width of the colour flow jet was 1.5 mm. Transoesophageal echocardiography with colour flow Doppler and Valsalva contrast studies therefore provides a sensitive method for the detection of residual atrial septal defects following balloon mitral valvuloplasty. Transatrial flow persists in the majority of these patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600989 TI - Late pulmonary haemodynamic changes in heart-lung transplantation. AB - As survival improves following heart-lung transplantation (HLT) the importance of obliterative bronchiolitis (OB) as a cause of late death increases. Whilst coronary occlusive disease (COD) may be less common in heart-lung transplant recipients than in patients receiving heart transplants, COD associated with OB can be lethal. We have studied 22 long-term survivors of heart-lung transplantation at an average of 25 months following transplantation during rest and at 50 W supine exercise and with prostacyclin induced vasodilation. Cardiac index increased less with exercise as the physiological measurement of OB using forced expiratory volume in one second (FEV1) fell (P = 0.018). Although resting pulmonary vascular resistance increased with falling FEV1, this increase was still within the normal range. We conclude that a fall in cardiac reserve on exercise accompanies the fall in FEV1 which characterizes OB and may reflect cardiac vascular disease. PMID- 1600990 TI - Valve replacement in octogenarians: increased early mortality but good long-term result. AB - Between January 1983 and December 1990, 20 patients aged 80 years or older underwent valvular surgery. The patients' ages varied from 80 to 87 years (mean, 82 +/- 1.5 years). The indication for operation was aortic stenosis in 19 patients, and mitral insufficiency after previous mitral valve replacement with a bioprosthesis in one. There were 15 elective, two urgent, and three emergency operations. Four of these patients had aortic valve replacement plus coronary artery bypass grafting. Six patients (30%) had an uneventful hospital stay, and the other 14 (70%) experienced several post-operative complications. The operative mortality rate was 15% (three patients). All patients before operation were in NYHA (New York Heart Association) class III and IV and all survivors remained in NYHA class I or II. The survivors have been followed from 6 to 70 months (mean 20 +/- 8 months). The actuarial survival rate at 1 and 5 years was 78.5% and 67%, respectively. Valvular replacement in octogenarians can be performed, despite the high rate of post-operative complications, with increased but acceptable mortality. Long-term results are good. PMID- 1600991 TI - Continuous ST- and QRS-vector changes and myoglobin release during streptokinase treated acute myocardial infarction. AB - Twenty-two consecutive patients with a first myocardial infarction treated with streptokinase (SK) were compared to a group of 33 consecutive patients who did not receive SK. Age, infarct localization, duration of symptoms and infarct size, as estimated by cumulative creatine kinase (CK) release, did not differ between the two groups. Myoglobin (MG) release stopped after 5.5 +/- 3.3 h in SK-treated patients, which was 11 h earlier than in the controls (P less than 0.0001). CK release ceased after 15 +/- 7.8 h, about 13 h earlier than in the controls (P less than 0.0001). ST and QRS vector changes, registered by continuous vectorcardiography, were completed after 2.9 +/- 2.0 and 4.4 +/- 2.5 h respectively, about 2 and 4 earlier than in the controls (P less than 0.005 and P less than 0.0001 respectively). With SK, the termination of ST and QRS vector changes occurred more uniformly than corresponding vector changes in the controls, in whom a longer time interval between the termination of ST and the end of QRS vector changes was observed. With SK, the difference between the end of ST and QRS vectors decreased by about 3 h to 1.6 +/- 1.5 h (P less than 0.0001). Temporal relations between MG release and ST and QRS vector changes were similar but more uniform than in those of the reference group. In conclusion, we found that SK resulted in an accelerated and more uniform development of the infarct process, ending about 10 h after onset of therapy, compared with 20-30 h in the reference group. PMID- 1600992 TI - Effects of mexiletine, propafenone and flecainide on signal-averaged electrocardiogram. AB - The effects of mexiletine, propafenone and flecainide on the parameters of signal averaged electrocardiogram in 40 subjects with symptomatic and repetitive ventricular arrhythmias were studied. Mexiletine (n = 16) suppressed ventricular arrhythmias in 10 patients and did not produce any significant changes in filtered QRS duration (fQRS), root mean square voltage of the final 40 ms of filtered QRS (RMS40) or low amplitude terminal component duration (LAS40). Acute (n = 8, 450 mg) and chronic (n = 16, 600-1200 mg.day-1) administration of propafenone determined a significant increase in fQRS (from 123 +/- 2.2 to 139 +/ 3 ms) and a reduction in RMS40 (from 54 +/- 8.8 to 34 +/- 6.7 microV); as a consequence the incidence of ventricular late potentials rose from 43 to 62%. The observed effects were independent of anti-arrhythmic efficacy, which was 86% for this drug. Acute (n = 8, 200 mg) and chronic (n = 13, 200-300 mg.day-1) administration of flecainide was associated with a marked prolongation in fQRS (from 123 +/- 2.8 to 138 +/- 4.1 ms) and a reduction in RMS40 (from 69 +/- 11.5 to 47 +/- 11 microV); thus determining an increase in the incidence of ventricular late potentials from 29 to 48%. Changes in signal-averaged electrocardiogram were not related to drug efficacy, which was 81%. These data indicate that 1c anti-arrhythmic drugs consistently modified the parameters of signal-averaged electrocardiogram; the observed changes might reflect an inhomogeneous slowing of intramyocardial impulse propagation. PMID- 1600993 TI - Efficacy and tolerability of gallopamil in coronary heart disease: a double blind cross-over comparison with nifedipine. AB - Anti-ischaemic properties and tolerability of the calcium antagonist gallopamil were compared with those of nifedipine in a double-blind cross-over study performed in 20 patients affected by effort or mixed angina. The patients were of both sexes and aged 43-66 years; coronary angiography performed on 18 of them revealed at least one-vessel disease (stenosis greater than 70%). After a one week wash-out period the patients received placebo for 2 weeks; thereafter 10 patients were treated orally with gallopamil 150 mg daily and 10 patients with nifedipine 60 mg daily for 4 weeks. Before crossing-over to the alternate therapy a 2-week placebo period was allowed. The patients underwent cycloergometric exercise tests after each phase of treatment; workload was increased by 25 W every 3 min and the test was stopped in the presence of a typical angina or ST segment depression or age-predicted maximal heart rate. The results show that both exercise time and maximal workload were significantly increased by gallopamil and by nifedipine in comparison with placebo; also the maximal ST segment depression was significantly reduced by the two drugs. The number of patients developing angina and/or segment depression during exercise test was significantly reduced by both drugs compared to placebo. Time to onset of angina and time to ST depression greater than or equal to 1 mm were increased, though not significantly, by both calcium antagonists. No side effects were recorded with gallopamil while with nifedipine six patients reported side effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600994 TI - Cyclosporine in heart transplant recipients: an exercise study of vasopressor effects. AB - The possible vasopressor effect of cyclosporine (CS) on both the systemic and pulmonary vascular beds has been investigated during bicycle exercise in 12 heart transplant recipients (mean age, 41 years) using pulmonary artery catheter measurements. Eight patients were taking cyclosporine and six azathioprine and prednisolone (AzS) as immunosuppressive therapy. With exercise, CS recipients show a significantly larger rise in systemic pressure than AzS recipients (P less than 0.001), with persistently higher pulmonary pressures (P less than 0.001). This suggests a generalized vasopressor effect of CS on the vasculature. PMID- 1600995 TI - The time sequence of electrical and mechanical activation during spontaneous beating and ectopic stimulation. AB - The relation between the sequence of electrical (E) and mechanical (M) activation was studied at the LV anterior wall of open-chest dogs (n = 11). M activation was defined as the onset of epicardial fibre shortening, as measured with a recently developed video technique. E activation was determined with a brush of extracellular electrodes. The delay between activation of basal and apical regions was consistently larger for M activation than for E activation: during spontaneous beating: 20.5 +/- 7.30 ms vs 8.8 +/- 3.31 ms, during right ventricular outflow tract pacing: 50.3 +/- 7.69 ms vs 39.0 +/- 5.31 ms and during left ventricular apex pacing 40.1 +/- 10.03 ms vs 25.4 +/- 9.30 ms, respectively (P less than 0.05 in all cases). The E-M time interval was consistently shorter in early than in late activated regions: 32 +/- 10 vs 41 +/- 8 ms during RV outflow tract pacing (P = 0.09) and 24 +/- 30 vs 40 +/- 24 ms during LV apex pacing (P less than 0.05). Electrical asynchronies larger than 40 ms resulted in decreases of systolic blood pressure and stroke volume. This study shows that the asynchrony of cardiac motion exceeds that of electrical activation because the time interval between electrical activation and onset of fibre shortening is larger the later a particular region is activated. Possible explanations for this phenomenon are discussed. PMID- 1600996 TI - Inhibition by trains of subthreshold high-frequency stimuli: an experimental study in spatial limitation. AB - The aim of this study was to determine whether the spatial limitation of the inhibitory effect of subthreshold conditioning stimuli trains (TSc) could be overcome by their simultaneous emission through several electrodes surrounding the area where the suprathreshold extrastimuli (S2) are delivered. In seven anesthaetized open chest dogs the effective ventricular refractory period was determined before and after the introduction of unipolar cathodal TSc, using epicardial electrodes. TSc pulse frequencies tested were 100 Hz, 200 Hz, 400 Hz, 600 Hz and 800 Hz, and train intensity was 10% lower than the train diastolic threshold for every pulse frequency. S2 and TSc were delivered: (a) by the same electrode; (b) by two different electrodes 3 mm apart; and (c) TSc through six peripheral electrodes surrounding the central electrode that delivered S2 (heptapolar electrode). Trains of 400 Hz showed the highest diastolic threshold, permitting the use of the highest train intensities. When TSc and S2 were delivered through the same electrode the ventricle remained unexcitable during the entire cardiac cycle in six of the seven dogs. In turn, when TSc and S2 were delivered by two different electrodes, the effective ventricular refractory period (EVRP) could only be increased by greater than or equal to 10 ms in three of the seven dogs (18 ms, 62 ms and 10 ms). When TSc was delivered simultaneously through six peripheral electrodes the increments were higher (118 ms, 88 ms and 75 ms) in these three dogs, and there was one additional dog with 12 ms increments of of EVRP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1600997 TI - The pathogenesis of atheroma and the rationale for its treatment. AB - Several theories have been proposed to explain the mechanism causing atheroma; these include endothelial cell injury, smooth muscle cell proliferation, lipid deposition and an abnormality of the vasa vasorum. Based on these hypotheses, new therapies aimed at causing regression or preventing the development of atheroma include heparin, calcium antagonists, beta-receptor antagonists, lipid lowering agents and drugs that manipulate platelets. PMID- 1600998 TI - Extreme underdevelopment of the left heart. The ultimate hypoplastic left heart syndrome. AB - We report a case of extreme underdevelopment of the left heart with a 12-day survival. At postmortem, neither a left atrium nor connecting pulmonary veins were identified. The left ventricle was only identified on histology. This was, effectively, a case of absence of the left heart. PMID- 1600999 TI - The myxoma syndrome: an unusual entity. A family study. PMID- 1601000 TI - Left posterior hemiblock related to an interventricular septum tumour. First case in the literature. AB - A 22-year-old man who engaged in intense and regular physical exercise complained of atypical chest pain. The only remarkable abnormality found in the routine clinical work-up was a left posterior hemiblock. The echocardiogram and the magnetic resonance imaging (MRI) study showed a tumour in the posterior and superior aspect of the interventricular septum where the posterior fascicle of the left bundle is located. It was interpreted that the left posterior hemiblock was produced by the tumour. PMID- 1601001 TI - Charles West (1816-1898). PMID- 1601002 TI - Medium-chain acyl-CoA dehydrogenase deficiency: molecular aspects. AB - Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an autosomal recessive disorder which is known to cause Reye-like syndrome in children and sudden infant death. A point mutation of lysine329-to-glutamic acid329 substitution in the MCAD gene was recently identified as the most common mutation in patients with MCAD deficiency. This mutation is responsible for about 90% of mutant MCAD alleles in Caucasians. Patients with this type of mutation have a variety of symptoms, indicating that the clinical heterogeneity of MCAD deficiency may not be caused entirely by genetic heterogeneity. Screening for the mutation among newborns in England, Australia, and United States of America indicates the prevalence of carriers to be 1 in 40-107, suggesting the high incidence of the mutation. Since presymptomatic diagnosis and appropriate dietary management are important in MCAD deficiency to prevent life-threatening complications, the relatively high incidence of this disorder may warrant population screening. The most common MCAD mutation can now be detected by DNA diagnostic methods using Guthrie cards. This makes it possible to screen a population efficiently for this potentially fatal disorder. PMID- 1601003 TI - Heart rate and oxygen uptake response to exercise in children with low peak exercise heart rate. AB - Normal children achieve the same increase of oxygen uptake (VO2) in response to exercise even though resting and submaximal exercise heart rates vary greatly as a function of age, body size and physical conditioning. To determine whether the VO2 response to exercise is altered when heart rate is significantly reduced by heart disease, we compared 78 children who achieved a peak exercise heart rate of less than or equal to 150 beats/min to 201 controls of similar body size and normal peak exercise heart rates of greater than or equal to 180 beats/min. All performed incremental (16.4 Watts/min) maximal cycle exercise. Separate analysis of males and females included heart rate, power (kg-m/min, Watts/kg), VO2 (ml/min, ml/min per kg), O2 pulse (VO2/heart beat), VE (l/min) and R (VCO2/VO2) at rest and during the 1st, 4th and last minute of exercise. Patients with low peak exercise heart rates had also lower resting submaximal exercise heart rates than controls. VO2 at comparable exercise levels did not differ from controls and consequently O2 pulse was greater in the patients than controls at rest and at all levels of exercise. A consistent gender difference was only found in controls where males achieved a higher VO2 and lower heart rates at comparable levels of exercise. The data show a normal exercise VO2 despite significantly lower heart rates. These findings cannot be explained by an increased arteriovenous difference alone and suggest that the patients retained the ability to effectively modulate stroke volume. PMID- 1601004 TI - Progressive high frequency hearing loss: an additional feature in the syndrome of congenital adrenal hypoplasia and gonadotrophin deficiency. AB - In an earlier report, we found that X-linked congenital adrenal hypoplasia may be associated with gonadotrophin deficiency. This combination has since been confirmed by many others. At the last examination, our patients were 22.4, 19.9 and 17.5 years old. They were doing well on replacement therapy with hydrocortisone, fluorohydrocortisone, and long-acting testosterone, but in all of them, a progressive hearing loss had appeared, starting at high frequencies at about 14 years of age. The loss progressed with age to lower frequencies, and the oldest patient had some remaining hearing capacity at 125-500 Hz only with a perceptive hearing loss of -95 dB at frequencies above 500 Hz. It is concluded that patients with this syndrome should be examined for hearing loss. X-linked adrenal hypoplasia may also be associated with glycerol kinase deficiency and myopathy. A molecular XP-deletion has suggested a locus for hypogonadotrophic hypogonadism distal to the glycerol kinase and adrenal hypoplasia loci. The observations in our patients suggest that the locus for at least this type of X linked deafness may be in the same area. PMID- 1601006 TI - Congenital hypopituitarism: results of pituitary stimulation tests and of magnetic resonance imaging in a newborn girl. AB - We report the case of a newborn girl in whom hypopituitarism was diagnosed in the neonatal period. Clinical, biological and radiological evidence suggested that hypopituitarism must have existed before delivery, yet MRI findings were similar to those described in older children with hypopituitarism of later onset. PMID- 1601005 TI - Corticosterone methyl oxidase type II deficiency: a cause of failure to thrive and recurrent dehydration in early infancy. AB - Corticosterone methyl oxidase type II (CMO II) deficiency is an uncommon cause of salt-wasting in infancy. We describe a boy who presented with recurrent dehydration and severe failure to thrive in the first 3 months of life, associated with mild hyponatraemia (serum Na+ 127-132 mEq/l) and hyperkalaemia (serum K+ 5.3-5.9 mEq/l). The diagnosis was suggested by an elevated plasma renin activity (PRA): serum aldosterone ratio, and subsequently confirmed by an elevated serum 18-hydroxycorticosterone: aldosterone ratio. Treatment with 9 alpha-fluorohydroxycortisone normalized growth parameters and PRA levels. CMO II deficiency should be considered in infants with recurrent dehydration and failure to thrive, even when serum sodium and potassium levels are not strikingly abnormal. PMID- 1601007 TI - Kawasaki-like disease in early course of acute monocytic leukaemia. AB - We report a rare occurrence of Kawasaki-like disease in an 11-year-old boy with acute monocytic leukaemia (AML). After 1 week of induction therapy with daunorubicin, etoposide, and cytosine arabinoside, the patient sequentially developed persistent fever, lymphadenopathy, conjunctival injection, exanthema, redness of the lips, and desquamation of the hands. Chest roentgenology showed cardiomegaly and an echocardiogram revealed a dilation of the left coronary artery. The patient was treated with high doses of gamma globulin and steroids. All symptoms except the coronary artery dilation improved. The symptoms did not recur on reinstatement of the original antileukaemia drugs. PMID- 1601008 TI - Transient IgG subclass deficiencies in newly diagnosed diabetic children. AB - In 27 children (15 males and 12 females) with insulin-dependent diabetes mellitus (IDDM), aged 1.2-13.5 years (mean 9.9 +/- 3.6 years) we investigated immunoglobulins (IgG, IgA, IgM), IgG subclass levels and islet-cell antibodies (ICA) at diagnosis and at 6 and 12 months after disease onset. At diagnosis, IgG levels were lower than -2SD in 7 patients (26%), IgA in 1 (3.7%), IgM in 1 (3.7%). IgG subclass levels were below the 3rd percentile in 13 patients (48.1%); in particular IgG1 in 7 (26%), IgG2 in 3 (11.1%), IgG3 in 2 and IgG4 undetectable in 1 case. In 3 out of the 13 patients combined IgG1-IgG3, IgG1-IgG2 and IgG1 IgG4-IgA deficiencies were observed. ICA were greater than 20 Juvenile Diabetes Foundation units in 17/27 patients. The HLA-DR2 frequency was higher in patients with IgG subclass deficiency than in patients with normal IgG subclass levels. During follow up, IgG levels normalized in 6 patients while IgA and IgM did not change. IgG1 normalized in 5 out of the 7 patients, IgG2 in all patients while IgG3 and IgG4 did not change. One year later ICA were still present in 8/27 patients. The hypogammaglobulinaemia and IgG subclass deficiencies observed in our patients could have either a genetic or an acquired basis. PMID- 1601009 TI - Antibodies to native type III collagen in the serum of patients with Kawasaki disease. AB - Pathological studies have revealed that the vasculitis in Kawasaki disease (KD) begins in the intima and the adventitia of blood vessels resulting in panvasculitis. In the present study we investigated the possibility that auto antibodies to types III and II collagen are involved in the vascular injury. Seven out of 38 patients (18%) with KD had elevated serum levels of IgG antibody to type III collagen. None had increased serum antibodies to type II collagen. Specificity of the antibody to type III collagen in patients with KD was 86%. Three out of seven KD patients (42.9%) with coronary complications had elevated serum levels of the antibody. It is conceivable that the more severe the inflammation of systemic blood vessels, the more frequently antibodies to type III collagen are detected and coronary complications develop. Accordingly, this antibody may be secondarily detected in the serum of KD when systemic blood vessels are severely damaged. Detection of antibodies to type III collagen might be a risk factor predicting coronary complications. PMID- 1601010 TI - Chronicity rate of hepatitis B virus infection in the families of 60 hepatitis B surface antigen positive chronic carrier children: role of horizontal transmission. AB - It is known that the 5%-10% of adults infected with hepatitis B virus (HBV) develop a chronic infection and that HBV infection acquired at birth by an hepatitis B surface antigen (HBsAg)/hepatitis B "e" antigen (HBeAg)-positive mother almost invariably leads to chronic infection. Little information is, however, available about the risk of HBV infection acquired in childhood becoming chronic. We have, therefore, studied the chronicity rate of HBV infection in the families of 60 consecutive HBsAg-positive chronic carrier children. Of parents 81.5% and 78.6% of children showed serological evidence of past or ongoing HBV infection. The chronicity rate was significantly higher among children (73.4%) than parents (35.6%). Such a high chronicity rate in these children was not correlated with vertical transmission, since this was reported in only 1.7% of them. It is noteworthy that the chronicity rate of HBV infection was not significantly different between children of HBsAg-positive mothers and those in whom infection must have been horizontally transmitted because their mothers were HBsAg-negative. Although the families studied represent a selected sample and the role of genetic factors could not be excluded, our results seem to show that the most important factor in determining the outcome of infection is the acquisition of hepatitis B during childhood. PMID- 1601011 TI - Combined deficiencies of the pyruvate dehydrogenase complex and enzymes of the respiratory chain in mitochondrial myopathies. AB - In six patients with mitochondrial (encephalo-) myopathy investigations of skeletal muscle revealed a defect of pyruvate dehydrogenase complex (PDHC) in combination with one or more respiratory chain complex deficiencies. A combination of defects of this kind has not been reported previously. Five of the six patients presented within the 1st year of life and had a severe clinical course. Intrafamilial variability of the clinical course in dizygotic twins both suffering from a cytochrome c oxidase deficiency and one of them also from a PDHC deficiency suggests an additional effect of PDHC deficiency on the clinical symptoms. Immunoblot studies of PDHC in five of the patients revealed no abnormalities in their subunit pattern, rendering a defect of mitochondrial protein import or assembly unlikely. The finding of a combined PDHC and respiratory chain deficiency has implications for the diagnostic approach, for therapy and genetic counselling. The exact pathogenetic mechanism of this combination of defects remains to be elucidated. PMID- 1601012 TI - Progressive cardiac failure following orthotopic liver transplantation for type IV glycogenosis. AB - Orthotopic liver transplantation (OLT) has been proposed to treat patients with type IV glycogenosis because of early progressive cirrhosis. Reports have shown absence of disease progression in other organs after OLT and even regression of cardiac amylopectin infiltration in one case. We describe a 15-month-old child in whom a liver transplant was performed for type IV glycogenosis. There were no clinical signs of extrahepatic disease before OLT. Nine months later, the patient developed progressive cardiac insufficiency and died from cardiac failure. Because of massive amylopectin deposits, decreased myofibrils in cardiac cells, and exclusion of other causes of cardiac failure, death was attributed to amylopectionosis. Our observation contrasts with the Pittsburgh experience and suggests that cardiac amylopectionosis may progress after OLT. PMID- 1601013 TI - Microscopic observations on tracheal aspirates from ventilated neonates. II. The onset of bronchopulmonary dysplasia and other changes. AB - A total of 450 undiluted and unprocessed tracheal aspirates from 120 intubated infants were examined microscopically for evidence of bronchopulmonary dysplasia and other changes. In 19 infants desquamated sheets of dysplastic epithelium in the fresh aspirate provided an early indication of developing bronchopulmonary dysplasia. Examination of unstained tracheal aspirates can provide, within minutes, information not only about the onset and development of bronchopulmonary dysplasia, but also provide evidence for milk or formula aspiration and for gastro-oesophageal reflux. PMID- 1601014 TI - Lack of temporal relation between acid reflux in the proximal oesophagus and cardiorespiratory events in sleeping infants. AB - We studied sleeping infants in order to investigate whether a temporal relation exists between acid reflux extending to the proximal portion of the oesophagus and cardiorespiratory events. One hundred infants with occasional regurgitations were studied: 50 infants admitted after an apparently life-threatening event (ALTE) that occurred during sleep and that remained unexplained despite medical investigation, and 50 asymptomatic infants (non-ALTE). The infants had a median age of 8 weeks (range 4-26 weeks); 54 were boys. In each child a pH probe was placed in the proximal portion of the thoracic oesophagus, under radiological control. Polygraphic monitoring of state of alertness, cardiorespiratory activity, and proximal oesophageal pH changes was conducted continuously during 1 night. The data were analysed blind. In 80 infants a total of 186 decreases in oesophageal pH below 4 units were seen; 37% occurred during wakefulness, and 40% during rapid eye movement (REM) sleep. A total of 7029 central and 61 obstructive apnoeas were monitored, mainly during REM sleep. Within 5 min before, and 5 min after the drops in pH, there was no difference in the number, or the duration of bradycardia, central, mixed, or obstructive apnoea. The infants with an ALTE could not be differentiated from the non-ALTE infants for any of the variables studied. It is concluded that spontaneous acid refluxes extending to the proximal portion of the oesophagus during sleep are usually not temporally related with the development of apnoeas or bradycardias. PMID- 1601015 TI - Immunosuppressive treatment for juvenile myasthenia gravis. AB - The result of immunosuppressive treatment in 20 cases of generalized myasthenia gravis with onset before age 16 were analysed. The patients age at the beginning of immunosuppressive treatment ranged from 10 to 22 years. Thirteen patients suffered from a severe form of myasthenia gravis with respiratory attacks, the remaining 7 demonstrated a moderately severe form with bulbar symptoms dominating the clinical picture. Indication for immunosuppressive treatment was lack of or only slight improvement after thymectomy. Prednisone was used in 17 cases, high dosage of methylprednisolone in 8 (in one case twice), azathioprine in 11 and cyclophosphamide in 10. Best results were obtained with cyclophosphamide since significant improvement was recorded in 14/20 of patients. Corticosteroids, i.e. prednisone and high-dose methylprednisolone proved to be of limited value. PMID- 1601016 TI - Nutritional vitamin B12 deficiency: two cases detected by routine newborn urinary screening. AB - We describe two asymptomatic newborns with nutritional vitamin B12 deficiency in whom increased urinary methylmalonic acid was detected by routine neonatal screening at 3 weeks of age. Both infants were exclusively breast-fed. One mother suffered from pernicious anaemia, and the other was a strict vegetarian. Both mothers had no clinical or haematological abnormality, aside from a borderline mean corpuscular volume for the vegetarian mother. This report illustrates the early appearance of functional vitamin B12 deficiency in breast-fed infants of vitamin B12-depleted mothers. It also demonstrates that urinary methylmalonic acid measurement is a sensitive indicator of tissue vitamin B12 deficiency. PMID- 1601017 TI - Neonatal theophylline intoxication: pharmacokinetics and clinical evaluation. AB - The pharmacokinetics of theophylline and its metabolites, caffeine, 1,3 dimethyluric acid, 1-methyluric acid and 3-methylxanthine were studied in a 5-day old 1.3 kg premature neonate who accidentally received 180 mg theophylline in 26 h during treatment for bradycardia. Tachycardia, hyperventilation, increased diuresis, central nervous system excitation, an increase in blood glucose concentrations followed by a prolonged decrease and hypercalcaemia were the predominant clinical and laboratory manifestations. The patient responded to supportive care and survived without sequelae. The concentration time course of theophylline and its metabolites in plasma and the pattern of urinary and gastric elimination were determined over 95 h. Theophylline showed, in contrast to its metabolites, a log linear decline in plasma. Elimination of theophylline and caffeine, calculated from their urinary excretion rates, were both exponential during the entire observation period. Urine flow dependence of renal clearance was obvious for theophylline and caffeine. Implications of theophylline disposition in neonates are discussed with special regard to theophylline poisoning. PMID- 1601018 TI - Cough and converting enzyme inhibitors. AB - Persisting cough developed in three children treated with converting enzyme inhibitors. The symptoms disappeared within 3-7 days after withdrawing medication. These observations in children complement previous reports in adults and indicate that cough may be induced by treatment with these agents. PMID- 1601019 TI - Adult respiratory distress syndrome associated with Mycoplasma pneumoniae infection. AB - A 13-year-old boy is described who developed severe adult respiratory distress syndrome (ARDS), biochemical pancreatitis and skin vasculitis after an acute respiratory infection due to Mycoplasma pneumoniae. The boy was mechanically ventilated for 17 days, but could be discharged in good clinical condition after 36 days of hospitalization. However, major disturbances of the lung function tests persisted, suggesting interstitial fibrosis. To the best of our knowledge, this is the first case of ARDS after M. pneumoniae infection in childhood. PMID- 1601020 TI - Standards of morphological evaluation and histological grading in experimental acute pancreatitis. AB - Acute pancreatitis is characterized morphologically by edema, hemorrhages, parenchymal necrosis and fat necrosis. The inflammation is accompanied by infiltration of polymorphonuclear leukocytes. According to the absence or presence of necrosis the disease can be divided into interstitial (or edematous) pancreatitis and hemorrhagic-necrotizing pancreatitis. The severity of disease can be graded in the histological sections either by giving scores to the different types of morphological alterations or by determining the proportion of necrotic tissue of the total lobular parenchyma. The former method is based on subjective assessment of histological slides and is suitable for the evaluation of both edematous and necrotizing pancreatitis. Histometric measurement of necrotic parenchyma can be used only in the necrotizing forms of experimental pancreatitis, e.g. in those induced by intraductal injection of bile, bile salts or digestive enzymes, and in the dietary ethionine-induced pancreatitis. Grading of the tissue damage is essential when the effects of different therapies are evaluated. PMID- 1601021 TI - The closed duodenal loop technique. AB - The closed duodenal loop (CDL) technique, one of the first experimental models producing experimental acute pancreatitis, is described in this article. Since this model was published first by Pfeffer in 1957, it has undergone several modifications. The CDL method is an easily practicable and reproducible model to investigate acute hemorrhagic pancreatitis. In view of other available experimental models, the CDL technique has lessened in popularity. PMID- 1601022 TI - Hormone-induced pancreatitis. AB - Intravenous infusion of the synthetic cholecystokinin analogue cerulein at a dose of 0.25 micrograms/kg/h causes maximal stimulation of pancreatic exocrine secretion. The infusion of supramaximal doses of cerulein (5 and 10 micrograms/kg/h) induces a significant increase in pancreatic enzymes in blood, and interstitial edema and inflammatory cell infiltration. This model of hormone induced pancreatitis works in rats, mice, dogs and hamsters. Besides intravenous infusion, repeated intraperitoneal injections can also be used for induction of pancreatitis. In the early phase of cerulein-induced pancreatitis, large autophagic vacuoles result from fusion of zymogen granules within the acinar cell. This is accompanied by an increase in lysosomal enzyme activity and activation of trypsinogen which finally leads to cellular necrosis. All animals survive the induction of pancreatitis. The pancreas completely regenerates within 6 days after induction of pancreatitis. This model of experimental pancreatitis favors the analysis of intracellular events in the early phase of pancreatitis. PMID- 1601023 TI - Acute experimental hemorrhagic-necrotizing pancreatitis induced by feeding a choline-deficient, ethionine-supplemented diet. Methodology and standards. AB - The present work evaluates the methodology and standards of acute hemorrhagic necrotizing pancreatitis induced by feeding a choline-deficient, ethionine supplemented (CDE) diet to mice. The diet model appears to be a good approximation of severe necrotizing human pancreatitis. Both the gross and histological appearance of the pancreatic and peripancreatic inflammation as well as the clinical and biochemical course of diet-induced pancreatitis resemble human disease. By limiting the period of feeding the diet, one can control the mortality at any desired level between 0 and 100%. Ascites, acidosis, hypoxia and hypovolemia occur in this model as well as in human pancreatitis. The time course of the morphological and biochemical alterations have extensively been studied and are, thus, well defined in this model. Despite the differences in pathogenesis of pancreatitis induced in this model versus human disease, the experimental pancreatitis and clinical pancreatitis share several pathophysiologic features. Therefore, the model is suitable to study pathophysiologic aspects of this disease. The diet model is particularly well suitable to study the potential for new therapeutic substances. The small size of the animals used, however, is a limitation for the evaluation of surgical procedures and of new diagnostic tools. Several pitfalls and problems have to be considered in order to obtain valuable data. The amount of injury produced by the CDE diet depends critically on sex, age and weight of the mice. Special care has to be taken to guarantee that the intake of the CDE diet is identical between different experimental groups. Therefore, each set of experiments needs to include a separate control group of mice which receive the CDE diet without any other special treatment. The potential benefit of an experimental therapy can be assessed by measuring survival, various biochemical and histological features, and alterations in hematocrit, pH and blood gases. PMID- 1601024 TI - The low-pressure duct perfusion model of acute pancreatitis. AB - The low-pressure duct perfusion model reliably produces acute pancreatitis in cats. The main pancreatic duct is made permeable in one of several ways: the perfusion of glycodeoxycholic acid along the main pancreatic duct, the administration of intragastric ethanol, the stimulation of pancreatic secretion into an obstructed duct, or the creation of acute hypercalcemia. Active pancreatic enzymes are then perfused through the main pancreatic duct via a catheter inserted into the duct in the tail of the gland, and acute edematous pancreatitis results. Simultaneous infusion of 16,16-dimethylprostaglandin E2 converts acute edematous into acute hemorrhagic pancreatitis. Histologically, the characteristic changes of human acute pancreatitis are manifest 24 h later: necrosis, polymorphonuclear leukocyte infiltrate, hemorrhage and edema. PMID- 1601025 TI - Vascular mechanisms to induce acute pancreatitis. AB - Vascular mechanisms are not standard tools to induce acute pancreatitis. They are used for special purposes to investigate the pathophysiologic significance of circulatory changes in acute pancreatitis. Because of the rich collateral network, occlusion of the main pancreatic arteries induces no pathological change. Complete occlusion of the venous outflow induces hemorrhagic necrosis of the pancreas, disturbances of the microcirculation, edema and focal parenchymal necrosis as in acute pancreatitis. In the last model, pancreatic and systemic alterations can be examined. PMID- 1601026 TI - Bile-induced pancreatitis. AB - The main bile-induced pancreatitis models are described with special attention to the duct injection models in dogs and the obstruction/reflux model in opossums. Practical problems of setup, study controls and monitoring are addressed. As for the opossum model, due to its clinical relevance the high variability of problems in the pathogenesis of pancreatitis that may be tackled by this model makes it a very useful, simple and not too expensive tool in the hands of a pancreatitis researcher. PMID- 1601027 TI - Role of oxygen radicals in experimental acute pancreatitis. AB - A growing body of evidence suggests that oxygen radicals are generated in all forms of experimental pancreatitis at an early stage of disease. Moreover, first indirect observations assume that also in human acute recurrent and chronic pancreatitis oxygen free radicals are generated and add to the damages seen. The source of the enhanced production of oxygen radicals remains still unclear. Experimentally, the efficiency of scavenger treatment varies between three different models, whereby these differences depend more on the design of the experimental models than on the form of pancreatitis which was induced. Antioxidant treatment with radical scavengers should therefore interrupt these deleterious pathomechanisms or at least mitigate the damages normally seen. Most studies, however, pretreated the experimental animals before inducing acute pancreatitis, which does not mirror the clinical reality. Patients, however, are admitted after onset of the disease. Therefore, well-defined, controlled clinical studies are needed to validate the involvement of oxygen radicals in acute and chronic pancreatitis and the effect of scavenger treatment in patients with pancreatitis. PMID- 1601028 TI - Clinical relevance of experimental acute pancreatitis. AB - There are several well-standardized models of experimental acute pancreatitis such as the closed duodenal loop technique, cholecystokinin or cerulein stimulation, duct injection and diet-induced acute experimental pancreatitis. With regard to human acute pancreatitis, experimental models in animals have a considerable high clinical relevance if the subject of investigation concerns pathogenetic, morphological and diagnostic approaches to the disease; as regards the treatment modalities and causative therapy of acute pancreatitis, experimental models in animals up to now seem to be far away from the clinical situation and therefore these protocols have low clinical relevance. The reasons for this discrepancy are outlined in this paper. PMID- 1601029 TI - Murine epidermal Langerhans cells are potent stimulators of an antigen-specific T cell response to Leishmania major, the cause of cutaneous leishmaniasis. AB - Cutaneous leishmaniasis is initiated by the bite of an infected sandfly and inoculation of Leishmania major parasites into the mammalian skin. Macrophages are known to play a central role in the course of infection because they are the prime host cells and function as antigen-presenting cells (APC) for induction of the cell-mediated immune response. However, in addition to macrophages in the dermis, the skin contains epidermal Langerhans cells (LC) which can present antigen (Ag) to T cells. Therefore, using a murine model of cutaneous leishmaniasis, we analyzed the ability of epidermal cells to induce a T cell response to L.major. The results demonstrated that freshly isolated LC, but not cultured LC, are highly active in presenting L.major Ag in vitro to T cells from primed mice and to a L.major-specific T cell clone. Furthermore, freshly isolated LC had the ability to retain L.major Ag in immunogenic form for at least 2 days. Their efficiency was much greater than that of irradiated spleen cells, a standard population of APC. LC stimulated both T cell proliferation and production of the lymphokines interleukin (IL)-2 and IL-4. The response was Ag specific and could be induced by lysate of L.major parasites and by live organisms. The data suggest that epidermal LC are important APC in cutaneous leishmaniasis. They may perform a critical function by capturing L.major Ag in the skin and presenting it either to quiescent T cells circulating through the draining lymph node or locally to T effector cells infiltrating the cutaneous lesion. PMID- 1601030 TI - Bee venom phospholipase A2-specific T cell clones from human allergic and non allergic individuals: cytokine patterns change in response to the antigen concentration. AB - Protein antigens with both allergenic and immunoprotective properties represent appropriate molecules to study IgE and IgG regulation. We have established a panel of T cell clones specific to bee venom phospholipase A2 (PLA) from human individuals allergic, hyposensitized or immune (protected) to bee sting. All clones obtained were CD3+, CD4+ and expressed alpha, beta T cell receptor. Depending on the T cell clone, maximal stimulation required 1 to 100 micrograms/ml of PLA, and the addition of interleukin (IL)-2 and/or IL-4 increased their antigen-dependent proliferation. Following antigen stimulation, the clones produced IL-4, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor. Most clones also produced tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor beta (TNF-beta), and some produced IL-5 and/or IL-2. Both absolute and relative amounts of secreted cytokines depended on the antigen concentration. At low antigen doses, IL-4 was produced but little or not IFN-gamma, whereas at higher PLA concentrations significant amounts of both IL-4 and IFN-gamma were obtained. Thus, these PLA-specific T cell clones could be classified according to the changes in the ratio of IL-4/IFN-gamma production in response to increasing antigen concentrations. Clones derived from allergic and hyposensitized individuals required higher critical amounts of antigen for IFN gamma induction, and expressed increasing IL-4/IFN-gamma ratios with increasing concentrations of PLA. Modulation of cytokine patterns by the dose of the antigen may be a driving force for IgE or IgG formation resulting in allergy or immunoprotection. PMID- 1601031 TI - Mycobacterial heat-shock proteins as carrier molecules. II: The use of the 70-kDa mycobacterial heat-shock protein as carrier for conjugated vaccines can circumvent the need for adjuvants and Bacillus Calmette Guerin priming. AB - In a recent work, we have shown that mycobacterial heat-shock proteins (hsp) of 65-kDa (GroEL-type) and 70-kDa (DnaK-type) acted as carrier molecules in mice, previously primed with Mycobacterium tuberculosis var. bovis (bacillus Calmette Guerin, BCG), for the induction of high and long-lasting titers of IgG against the repetitive malaria synthetic peptide (NANP)40. Anti-peptide antibodies were induced when the malaria peptide, conjugated to the mycobacterial hsp, was given in the absence of any adjuvants (Lussow et al., Eur. J. Immunol. 1991. 87:2960). In this report, we show that mice immunized with peptides or oligosaccharides conjugated to the 70-kDa hsp produced high titers of IgG antibodies in the absence of any previous priming with BCG. The anti-peptide antibody response persisted for at least 1 year. This adjuvant-free carrier effect of the 70-kDa hsp was T cell dependent, since no anti-peptide nor anti-70-kDa IgG antibodies were induced in athymic nu/nu mice. Previous immunization of mice with the 65-kDa or 70-kDa hsp did not have any negative effect on the induction of anti-peptide IgG antibodies after immunization with hsp-peptide conjugates in the absence of adjuvants. Furthermore, preimmunization with the 65-kDa hsp could substitute for BCG in providing an effective priming for the induction of anti-(NANP) antibodies. Finally, both the 65-kDa and 70-kDa hsp acted as carrier molecules for the induction of IgG antibodies to group C meningococcal oligosaccharides, in the absence of adjuvants. These findings strongly suggest that the use of hsp as carriers in conjugated constructs for the induction of anti-peptide and anti oligosaccharide antibodies could be of value in the design of new vaccines for eventual use in humans. PMID- 1601032 TI - Secretion of interleukin-8 following phagocytosis of Mycobacterium tuberculosis by human monocyte cell lines. AB - Tuberculosis is a major cause of mortality worldwide and incidence is increasing as a result of the AIDS epidemic. Cytokines such as tumor necrosis factor (TNF) are important in the host response to Mycobacterium tuberculosis. TNF is involved in both granuloma formation and has direct anti-mycobacterial activity. This study investigated the secretion of interleukin (IL)-8 following phagocytosis of M. tuberculosis by a human monocytic cell line and by a more phenotypically mature macrophage-like cell line. M. tuberculosis is shown to be a more potent inducer of IL-8 but not of TNF than bacterial lipopolysaccharide in vitro in both cell types. IL-8 production is partly a consequence of accumulation of mRNA coding for this cytokine. Secretion of IL-8 is not a simple consequence of the phagocytic process but due to the specific interaction M. tuberculosis and the monocyte. IL-8 production was independent of TNF and of virulence of the strain of M. tuberculosis. IL-8 secretion following phagocytosis of M. tuberculosis suggests that this cytokine may be involved in granuloma formation in vivo, possibly acting, in part, as a T cell chemoattractant. PMID- 1601033 TI - Cell surface display of rat invariant gamma chain: detection by monoclonal antibodies directed against a C-terminal gamma chain segment. AB - A series of 14 monoclonal antibodies (mAb) directed against the C-terminal part of the rat invariant gamma chain (amino acid 142-216) was generated using distinct fusion proteins that contain this gamma segment for immunization and hybridoma screening. Additional fusion protein were prepared carrying discrete regions of the gamma chain. Employing these reagents confirmed that the obtained mAb do indeed recognize the C-terminal portion of the invariant chain, as demonstrated by Western blot analysis. All mAb established recognize epitopes present on the native gamma chain, as revealed by immunoprecipitation analysis using nonionic detergent extracts of metabolically labeled Lewis rat splenocytes combined with two-dimensional gel electrophoresis. However, while the majority of the gamma chain-specific mAb precipitated gamma chain-containing polypeptide chain complexes in which immature, sialic acid-deficient and mature, terminally sialylated forms of the gamma chain were predominantly represented, a fraction of the antibodies preferentially precipitated the immature gamma forms. Cell surface binding of these two groups of mAb correlated with the immunoprecipitation data in that the former group of antibodies did bind to intact Lewis rat spleen cells, while essentially no binding was observed with the antibodies of the latter group. Double-fluorescence staining with the class II-specific fluorescein isothiocyanate-conjugated mAb OX3 and OX6, respectively, as well as a representative gamma chain-specific mAb visualized with phycoerythrin-coupled secondary antibody shows coexpression of class II determinants and the invariant chain at the cell surface. PMID- 1601034 TI - Interaction of C1q receptor with lung surfactant protein A. AB - Earlier we reported the purification of C1q receptor (C1qR) from U937 cells and human tonsil lymphocytes (Malhotra, R. and Sim, R. B., Biochem. J. 1989. 218: 625) and showed that C1qR interacts with the ligands C1q, mannose-binding protein, conglutinin and lung surfactant protein A (SP-A) (Malhotra, R., Thiel, S., Reid, K. B. M. and Sim, R. B., J. Exp. Med. 1990. 172: 955). C1qR was characterized as an acidic glycoprotein, which, when solubilized, exists as a dimer of Mr 115,000 under non-denaturing conditions. In this article we provide evidence for binding of radioiodinated SP-A to U937 cells and show that binding of radioiodinated SP-A to U937 cells is specific, saturable, salt dependent and is inhibited by purified C1qR and by C1q. The interaction of SP-A with U937 cells was found to up-regulate the surface expression of C1qR. Incubation of SP-A with U937 cells at 37 degrees C for 80 min was found to increase the receptor number per cell. Increase in receptor number was inhibited in the presence of sodium azide and monensin. Incubation of cells with calcium ionophore A23187 induced increased surface expression in the absence of SP-A. The results indicate that interaction of SP-A with U937 cells triggers the expression of an intracellular pool of C1qR. PMID- 1601035 TI - Cytokine enhancement of complement-dependent phagocytosis by macrophages: synergy of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor for phagocytosis of Cryptococcus neoformans. AB - We have examined the regulation of complement dependent phagocytosis by macrophage-activating cytokines. Tumor necrosis factor (TNF)-alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF), but not interferon gamma, interleukin-4 or macrophage-CSF, stimulated ingestion of the encapsulated fungal pathogen Cryptococcus neoformans by resident peritoneal macrophages in vitro. This was dependent upon opsonization of the yeasts with complement, 72 h of incubation with the cytokines for maximum effect, and the obligate involvement of the macrophage CR3 receptor. TNF-alpha and GM-CSF synergized at low concentrations, resulting in dramatic up-regulation of phagocytosis when compared to either cytokine alone. Supernatants from C. neoformans-specific T cells also increased macrophage phagocytic efficiency. Finally, the administration of neutralizing mAb specific for TNF-alpha and GM-CSF increased mortality in C. neoformans-infected mice, and induced the rapid progression of disease with involvement of the brain and meninges. We conclude that TNF-alpha and GM-CSF are potent regulators of complement-dependent phagocytosis by murine macrophages. Macrophage activation with these two cytokines can completely overcome the anti phagocytic properties of the virulent yeasts. Our results, therefore, implicate TNF-alpha and GM-CSF as important mediators of resistance to encapsulated pathogens such as C. neoformans where ingestion of the organism is a critical process in host resistance. PMID- 1601037 TI - Tissue-specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing. AB - CD46 (membrane cofactor protein) is a human cell surface glycoprotein with cofactor activity for factor I-mediated cleavage of complement components C3b and C4b. The CD46 protein from normal lymphocytes resolves on sodium dodecyl sulfate polyacrylamide gel electrophoresis as two major bands of 66 and 56 kDa. CD46 cDNA encodes four extracellular short consensus repeat domains, a Ser/Thr/Pro (STP) rich region, a transmembrane region and a cytoplasmic tail. We now show that exquisite control of mRNA splicing is responsible for the heterogeneous expression of CD46 isoforms. Differential splicing of 5 exons generates at least 14 CD46 mRNA variants whose expression is stringently regulated by allelic, tissue-specific and malignancy-related factors, as: (a) leukemic cells and Epstein-Barr virus-transformed B cells preferentially incorporate the first of three STP exons (exon 7) into mRNA, and produce a larger CD46 isoform of 74 kDa, (b) an allelic difference in the proportion of 66- and 56-kDa CD46 isoforms on lymphocytes corresponds to the preferential inclusion or exclusion of the second STP exon (exon 8), (c) the third STP exon (exon 9) is specifically deleted in some placentae, (d) spermatozoa delete both exons 12 and 13, encoding a shorter transmembrane region and a unique cytoplasmic tail and (e) all tissues tested differentially splice exon 13, resulting in two alternative cytoplasmic tails. The distribution of the 14 alternatively spliced RNA transcripts correlated with the presence of protein isoforms of the predicted size, indicating that alternative splicing leads to heterogeneity of CD46 glycoproteins. PMID- 1601036 TI - Immunity after treatment of human schistosomiasis: association between IgE antibodies to adult worm antigens and resistance to reinfection. AB - Previous studies in school children have demonstrated the slow development with age of resistance to reinfection after chemotherapy of Schistosoma mansoni infections, and have indicated that inappropriate ("blocking") antibody responses prevent the expression of immunity in young children. The present study was designed to investigate further the nature of the protective responses, by serological studies on a group of 151 S. mansoni-infected individuals resident in an endemic area in Machakos District, Kenya. Antibody levels against various antigens in blood samples before treatment were related to intensity of previous infections; antibodies in blood samples taken 6 months after treatment were related to cumulative reinfection rates over the following 30 months. IgE against an adult-worm antigen preparation correlated positively with age and negatively with reinfection. In contrast, IgE antibodies against other life-cycle stages showed either no relationship or the reverse correlation. Furthermore, antibodies of other isotypes against adult-worm antigens showed no correlations with reinfection. The correlation with IgE could be demonstrated for different preparations of adult worms, including a periodate-treated preparation presumptively depleted of carbohydrate epitopes. For both the intact and the periodate-treated preparations, multiple regression analysis of the results for children less than or equal to 16 years old demonstrated an IgE effect after allowing for age, although this effect was not observed in a previously studied group of school children. Western blot analysis of the adult-worm preparation revealed a limited set of antigens recognized by IgE, among which an antigen of 22 kDa was prominent. The qualitative presence of IgE against this antigen could also be shown to be related to a lack of subsequent reinfection. PMID- 1601038 TI - Antigen processing for presentation by class II major histocompatibility complex requires cleavage by cathepsin E. AB - Proteolytic degradation (processing) of antigen by antigen-presenting cells is a major regulatory step in the activation of a T lymphocyte immune response. However, the enzymes responsible for antigen processing remain largely undefined. In this study we show that cathepsin E, and not the ubiquitous lysosomal cathepsin D, is the major aspartic proteinase in a murine antigen-presenting cell line, A20. This enzyme is localized to a non-lysosomal compartment of the endosomal system in these cells. Functional studies using a highly specific inhibitor of cathepsin E show that this enzyme is essential for the processing of ovalbumin by this cell line. Thus, cathepsin E, whose function was hitherto unknown, may play a major role in antigen processing. PMID- 1601039 TI - T cell recognition of donor major histocompatibility complex class I peptides during allograft rejection. AB - LEW (RTI1) recipients of DA (RTIav1) skin and kidney allografts were tested for the capacity of their T lymphocytes to proliferate to three 22-24-amino acid peptides from the hypervariable regions of the RTI-Aav1 classical MHC class I molecule. Ten days after rejecting second-set DA kidney allografts, spleen cells (but interestingly not lymph node cells) from LEW recipients showed strong, LEW antigen-presenting cell-dependent, CD4+ T cell proliferation to peptide 1 (from the alpha helical region of the alpha 1 domain). CD8+ T cells showed no response to peptide 1. There was no response by the spleen cells to peptide 2 (from the beta sheet of the alpha 2 domain) or peptide 3 (from the alpha helical region of the alpha 2 domain). Immunization of LEW rats with pure RTI-Aav1 class I H chain in Freund's adjuvant gave responses identical to that seen after grafting, i.e. good CD4+ T cell proliferation to peptide 1, but none to peptides 2 and 3. However, immunization of LEW rats with peptides 1, 2 and 3 in Freund's adjuvant resulted in good CD4+ T cell proliferation responses to each of the peptides. These data demonstrate that indirect allorecognition can be stimulated by allograft rejection, and emphasize that the physiological processing of donor antigens will influence which peptides will be important in indirect allorecognition in transplantation. PMID- 1601040 TI - Soluble anti-mu monoclonal antibodies prime resting B cells to secrete immunoglobulins in response to interleukins-4 and -5. AB - Soluble anti-immunoglobulin (Ig) antibodies have been generally found to inhibit Ig secretion in B cells, via largely unknown mechanisms. To investigate this phenomenon further a two-step culture system was used in which B cells are primed for 24-72 h with various soluble monoclonal or polyclonal anti-Ig antibodies: after washing the cells were placed in readout cultures with a combination of interleukin (IL)-5 and IL-4. Using this protocol B cells primed with (mitogenic or nonmitogenic) anti-mu monoclonal antibodies differentiated into large numbers of IgM-secreting cells, comparable to responses to lipopolysaccharide. In contrast, priming with polyclonal rabbit anti-Ig or monoclonal anti-kappa antibodies, markedly inhibited Ig secretion induced by IL-4 + IL-5. In addition, anti-mu was markedly inhibitory if left in the readout cultures with the two lymphokines. These results, therefore, indicate that appropriate cross-linking of surface IgM receptors on B cells can prime the cells to secrete Ig when they are restimulated by T cell-derived lymphokines in the absence of anti-mu. In contrast co-ligation of both surface IgM and surface IgD receptors apparently results in powerful inhibition of Ig secretion, which is not reversed by stimulation with IL 4 plus IL-5. PMID- 1601041 TI - Characterization of two human monoclonal IgM antibodies that recognize nuclear lamins. AB - Using immunofluorescence and immunoblotting techniques, we have identified monoclonal IgM lambda from two patients that are specific for lamins A and C and lamin B, respectively. Lamins A, B, and C are peripheral membrane proteins of the nuclear envelope with structural similarities to cytoplasmic intermediate filament proteins. When studied by indirect immunofluorescence on rat tissues, the serum containing anti-lamin B IgM stained smooth and striated muscles in addition to nuclear envelopes. Lamin B antibodies affinity purified from this serum were able to label muscle cells, suggesting that lamin B shares an epitope(s) with an unidentified muscular component(s). Since in an enzyme-linked immunosorbent assay there was no reactivity with a panel of proteins which are frequent targets of "natural" antibodies, these monoclonal IgM appear to belong to the rare category of IgM that possess a restricted specificity. PMID- 1601042 TI - Ongoing V kappa-J kappa recombination after formation of a productive V kappa-J kappa coding joint. AB - V kappa genes of man can recombine with the J kappa gene segments either by an inversion or by a deletion mechanism. Back-to-back fusion products of the respective recombination signal sequences (signal joints) are retained on the chromosome after the formation of a V kappa-J kappa coding joint by an inversion. Our knowledge of the structure of the human kappa locus and the application of the polymerase chain reaction allowed us now to establish a direct relationship between different kappa recombination products in the lymphoid cell line JI. Two consecutive inversions fully explain the existence of two coding joints and two signal joints on the same chromosome of this cell line. Although the initially formed coding joint is productively rearranged and expressed, a second V kappa-J kappa rearrangement took place which leads to an aberrant joint. In this process a J kappa gene segment of the signal joint that had been created in the first V kappa-J kappa joining was used as the recombination target. The sequence of the two rearrangements is unequivocal since a product of the first (productive) reaction is a partner in the second (aberrant) one. PMID- 1601043 TI - The monoclonal antibody ER-BMDM1 recognizes a macrophage and dendritic cell differentiation antigen with aminopeptidase activity. AB - Here we describe the reactivity of monoclonal antibody (mAb) ER-BMDM1, directed against a 160-kDa cell membrane-associated antigen (Ag) with amino-peptidase activity. The aminopeptidase recognized by ER-BMDM1 is present on various mouse macrophage (M phi) and dendritic cell (DC) subpopulations as well as on microvillous epithelia. Analysis of ER-BMDM1 Ag expression in in vitro models of M phi maturation revealed that the Ag is expressed at increasing levels upon maturation of M phi. In vivo, high level expression of the ER-BMDM1 Ag occurs after the monocytic stage of maturation, since bone marrow cells and peripheral blood monocytes are essentially ER-BMDM1 negative. Analysis of isolated-resident and elicited M phi populations showed that ER-BMDM1 recognizes a specific subpopulation of mature M phi: only some resident peritoneal and alveolar M phi are ER-BMDM1 positive, whereas virtually all thioglycollate-elicited peritoneal exudate M phi bind the mAb. In lymphoid organs, a subpopulation of M phi is recognized as well as interdigitating cells (IDC) located in T cell areas. Phenotypic analysis of isolated DC--the in vitro equivalents of IDC--from spleen and lymph nodes confirmed that the majority of this important antigen-presenting cell population expresses the ER-BMDM1 aminopeptidase. The molecular characteristics of the ER-BMDM1 Ag suggest that it may represent the mouse homolog of human CD13. PMID- 1601044 TI - Non-random features of the repertoire expressed by the members of one V kappa gene family and of the V-J recombination. AB - The 5' and 3' flanking sequences of 14 members of the V kappa Ox (VK 4/5) gene family of BALB/c mice have been established. The family was unusual in the number of bases between the codon for Pro 95 and the heptamer sequence; most members contained four but there were also examples of none. A conserved leader sequence was used to amplify the genomic DNA of rearranged genes in order to analyze the spleen B cell repertoire of non-immunized animals. The library contained many members with virtually identical sequences to one or other of the already known members of the family. In addition, there were repeats of other sequences, allowing the definition of 12 hitherto undefined members of the family. Only 3 out of 96 could have originated by gene conversion, or as artefacts of the amplification procedure, and only 2 were putative somatic mutants. The frequency of expression of different members of the V kappa Ox gene family was not random, and some germ-line genes were unrepresented in the library. The high frequency of V kappa Ox1-J kappa 5 is in line with the dominance of this combination in the oxazolone response. An analysis of the junctional segment showed that although in most cases the diversity was due to trimming, there were exceptions indicating de novo additions (N or P bases). The average number of bases trimmed from the V kappa and the J kappa segments was not the same. There was no correlation in the number of bases trimmed from V kappa or J kappa in each recombination. The implications of asymmetric trimming in terms of the mechanism of recombination are discussed. PMID- 1601045 TI - Cytotoxic T lymphocytes against the antigen-processing-defective RMA-S tumor cell line. AB - RMA-S is an antigen processing-defective cell line, obtained from a Rauscher virus-induced tumor. The cells express only a low level of cell surface major histocompatibility complex (MHC) class I molecules, which are supposed to be devoid of internally derived antigenic peptides. We investigated Rauscher virus expression and Rauscher peptide presentation to virus-specific cytotoxic T lymphocytes (CTL) by this cell line. Viral proteins are expressed properly, both intracellularly and at the cell surface of RMA-S. Rauscher peptides are presented to virus-specific CTL in the groove of both the class I H-2Kb and Db molecules, but at a low level. Culture of RMA-S cells at room temperature increases their susceptibility to CTL. The RMA-S defect thus affects, but not totally abrogates, Rauscher peptide presentation by MHC class I molecules via the endogenous pathway. This indicates that the RMA-S antigen processing deficit is not absolute. PMID- 1601046 TI - A cross-species functional interaction between the murine major histocompatibility complex class I alpha 3 domain and human CD8 revealed by peptide-specific cytotoxic T lymphocytes. AB - The monomorphic cell surface glycoprotein CD8 acts as co-receptor in the recognition of peptide-major histocompatibility complex (MHC) class I complexes by cytotoxic lymphocytes (CTL) by binding to the monomorphic alpha 3 domain of the class I molecule. Positions 227 and 245 in the class I alpha 3 domain appear to be especially important for this interaction. Recent reports suggest there is no interspecies recognition between CD8 and MHC class I. In this study, hybrid genes from human class I HLA-A0201 and murine class I H-2Kb were transfected into human and mouse cells and tested in Cr-release assays using HLA-A0201-restricted influenza A matrix peptide-specific CTL as effectors. Transfected cells expressing chimeric genes comprising the alpha 1 and alpha 2 domains from HLA A0201 together with the H-2Kb alpha 3 domain were lysed as effectively as wild type HLA-A0201 and in both cases, killing was blocked by anti-CD8 antibody equally well. These results indicate that human CD8 can interact with the alpha 3 domain of murine class I to the same level as human class I. PMID- 1601047 TI - High frequency of cord blood lymphocytes against mycobacterial 65-kDa heat-shock protein. AB - A high frequency of nonadherent mononuclear cells in human cord blood proliferates in response to mycobacterial 65-kDa heat-shock protein. The frequency range in cord blood is not different from that in peripheral blood of Bacillus Calmette-Guerin vaccinated adults. In comparison we found 10 to 100 times lower frequencies to purified protein derivative in nonadherent cord blood mononuclear cells than in adult peripheral blood mononuclear cells. These findings may provide experimental support for Cohen's theory of the immunological homonculus. PMID- 1601048 TI - Functional role of intravascular coronary endothelial adenosine receptors. AB - The endothelium is relatively 'impermeable' to adenosine. In addition, infusion of adenosine deaminase and transient infusion of large size adenosine agonists (molecular weight 100 kD) which are confined to the intravascular space depress effects of endogenous adenosine and retain physiologic activity respectively. Accordingly, the concept that intravascular adenosine may exert some of its action on the capillary lumen was tested by coupling the agonists: N6 ([aminoethylamino]carbonyl)methylphenyladenosine (ADAC) and N6-octylamine adenosine (NOA) to carboxylated latex microspheres (0.07 microns diameter); thus, insuring their intravascular confinement. Our results demonstrated that sustained infusion of these particles into isolated saline perfused guinea pigs hearts caused a decrease in coronary vascular resistance, ventricular contraction, spontaneous ventricular rhythm, inhibition of auricular ventricular transmission and glycolytic flux. These effects were reversible and specific since microspheres without purines had no effect and the adenosine antagonist sulphophenyltheophylline blocked these responses. Furthermore, the effects were not the result that during the passage of the sphere-agonist complex through the heart the covalent bond hydrolyzed, releasing free agonist. Our data indicate that selective activation of intravascular coronary purine receptors may cause the release of endothelial bioactive messengers that regulate the function and metabolism of vascular and cardiac cells. PMID- 1601049 TI - Airway pharmacology of the potassium channel opener, HOE 234, in guinea pigs: in vitro and in vivo studies. AB - The smooth muscle relaxant effects of the novel potassium channel opener, HOE 234, were investigated in guinea pig airways and compared with those of lemakalim (BRL 38227). Both agents evoked concentration-related reduction in spontaneous tracheal tone or in the tone induced by histamine, prostaglandin E2 or carbachol. HOE 234 was more potent, particularly against carbachol, and was considerably longer acting than lemakalim in a wash-out experiment. On testing for preventive efficacy against histamine-induced bronchoconstriction in anaesthetized animals a dose-related decrease of pulmonary resistance (RL) was observed. HOE 234 given either intravenously (i.v.) or by inhalation was longer acting and 3 and 6 times more potent than lemakalim. Administration of 30 micrograms/kg i.v. HOE 234 during continuous bronchoconstriction maintained by infusion of histamine decreased RL for more than 20 min whereas the effect of 100 micrograms/kg i.v. lemakalin disappeared within 4 min. These results show that HOE 234 is effective against contractile response induced by asthma mediators in guinea pig airways and compares favourably with lemakalim. Moreover it acts on acute existing bronchospasm and therefore has the potential to act against asthma attacks. PMID- 1601050 TI - Protective effects of an alpha-tocopherol analogue against myocardial reperfusion injury in rats. AB - Free radicals may cause part of the irreversible injury which occurs during myocardial infarction and reperfusion. In the present study MDL 73404, an alpha tocopherol analogue which is a free radical scavenger has been evaluated for its effects on infarct size in an anaesthetised rat model of coronary artery ligation (60 min) and reperfusion (30 min). Intravenous infusion of the compound began 10 min before occlusion until the end of reperfusion. MDL 73404 (0.3-3 mg/kg per h) reduced infarct size, although not in a dose-related manner. Infusion of MDL 73404 (3 mg/kg per h) commencing 30 min before reperfusion until the end of reperfusion also induced a significant reduction in infarct size. In the isolated rat heart (Langendorff technique) subjected to 30 min no-flow global ischaemia, pretreatment with MDL 73404 (0.03 and 0.1 mM) in the perfusion buffer and during 30 min of reperfusion resulted in a significant increase in the maximal pressure development (+dP/dt max) and relaxation (-dP/dt max), left ventricular systolic pressure and heart rate during reperfusion, whereas left ventricular diastolic pressure was significantly reduced. In contrast, only one control heart out of five exhibited signs of recovery. Replacement, for 2 min, with a cardioplegic solution before the 30 min period of ischemia resulted in an increased heart rate and contractility during reperfusion compared to hearts that did not receive the cardioplegic solution. The presence of MDL 73404 (0.03 and 0.1 mM) in the perfusion fluid induced an additional increase in left ventricular systolic pressure to the pre-ischaemic levels. MDL 73404 may have potential for cardioprotective use in acute reperfusion of the myocardium following ischaemia. PMID- 1601051 TI - RP 59227, a novel PAF receptor antagonist: effects in guinea pig models of airway hyperreactivity. AB - The PAF antagonists RP 59227 and WEB 2086 (100 micrograms.kg-1 i.v., 10 min prior to platelet-activating factor (PAF) infusion) abolished or reduced (P less than 0.05) hyperreactivity to bombesin measured at 1 h. Similarly, RP 59227 and WEB 2086 (10 mg.kg-1 p.o., 1 h prior to PAF aerosol) abolished or reduced (P less than 0.01) hyperreactivity to bombesin measured at 24 h. Lower concentrations of RP 59227 and WEB 2086 (3 mg.kg-1 p.o.) were without effect. RP 59227 or WEB 2086 (3 or 10 mg.kg-1 p.o., 1 h prior to antigen aerosol) did not protect against antigen-induced hyperreactivity to histamine measured at 24 h. Antigen-(but not PAF)-induced hyperreactivity was accompanied by an increase in total cell number and, specifically, eosinophil number in bronchoalveolar lavage fluid. The PAF antagonists did not affect BALF cell populations. It is concluded that RP 59227 and WEB 2086 are potent PAF antagonists which inhibit PAF-but not antigen-induced airway hyperreactivity. These data suggest that endogenous PAF may not be involved in antigen-induced hyperreactivity in the guinea pig. PMID- 1601052 TI - Cloricromene, a coumarine derivative, protects against lethal endotoxin shock in rats. AB - Endotoxin shock was induced in male rats by an intravenous (i.v.) injection of Salmonella enteriditis lipopolysaccharide (LPS; 20 mg/kg i.v.). Survival rate, macrophage and serum tumor necrosis factor (TNF-alpha), mean arterial blood pressure (MAP) and white blood cell count were then evaluated. Furthermore the in vitro effect of cloricromene on peritoneal macrophage phagocytosis and TNF-alpha release by primed peritoneal macrophages was investigated. LPS administration caused animal death (0% survival 24 h after endotoxin challenge), hypotension, marked leukopenia and increased the levels of TNF-alpha in both serum and macrophage supernatants. Cloricromene administration (0.5, 1 and 2 mg/kg i.v. 15 min after endotoxin) protected against LPS-induced lethality (100% survival rate 24 h after endotoxin challenge), reverted LPS-induced hypotension and leukopenia, and decreased TNF-alpha in both serum and macrophage supernatants. Finally, cloricromene, added in vitro to peritoneal macrophages collected from endotoxin treated rats increased macrophage phagocytosis and reduced TNF-alpha formation by activated mononuclear phagocytes. Our data suggest that cloricromene increases survival rate in endotoxin shock through an inhibition of TNF-alpha production. PMID- 1601053 TI - Pharmacological characterization of a new highly potent B2 receptor antagonist (HOE 140: D-Arg-[Hyp3,Thi5,D-Tic7,Qic8]bradykinin). AB - HOE 140 (D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a new B2 antagonist, was compared to R-493 (D-Arg[Hyp3-D-Phe7,Leu8]bradykinin) with respect to inhibition of the responses of seven isolated smooth muscle preparations to bradykinin. R 493 was found to exert: (a) high antagonistic activity on the rabbit jugular vein (pA2 of 8.86), (b) moderate activity on the rabbit aorta, guinea-pig ileum, hamster urinary bladder and human urinary bladder (pA2 of 5.76, 6.77, 7.16 and 7.15, respectively) and (c) a stimulatory effect on the guinea-pig trachea. On the other hand, HOE 140 showed identical apparent affinities (8.36-9.12) on all preparations except the rabbit aorta where it was inactive and the guinea-pig trachea where the compound was an antagonist (pA2: 7.42) without agonistic effect. HOE 140 is specific and selective for B2 receptors since it was inactive against angiotensin II, substance P, neurokinin A, desArg9-bradykinin, noradrenaline or acetylcholine in the various preparations. R-493 inhibited the contractile effects of bradykinin competitively, while HOE 140 was not competitive even at low concentrations (7.7 x 10(-9) M). These results demonstrate that HOE 140 is a potent B2 antagonist with high affinity, specific for kinin receptors and selective for the B2 receptor type, but is non competitive. HOE 140 is the first bradykinin receptor antagonist that acts as such on the guinea-pig trachea without showing any agonistic activity. PMID- 1601054 TI - Cardiovascular responses elicited by intrathecal kinins in the conscious rat. AB - In the conscious, unrestrained rat, intrathecal (i.t.) injection of 0.81 pmol-81 nmol bradykinin (BK), kallidin (KD) and T-kinin at the T-9 spinal cord level produced transient (less than 10 min) increases in mean arterial pressure (MAP) and longer lasting decreases in heart rate (HR). These effects were dose dependent and similar with respect to intensity and time course for the three kinins. The des-Arg9-BK fragment, a selective agonist for B1 receptors, was active only at 81 nmol. The pressor response induced by BK was enhanced by propranolol and by transection of the cervical spinal cord but was converted to a vasodepressor effect by prazosin. The bradycardia was converted to tachycardia by prazosin, atropine, pentolinium, capsaicin and in spinal transected rats. However, the cardiovascular responses to BK remained unaffected by diphenhydramine plus cimetidine, morphine, indomethacin, adrenal medullectomy, i.t. idazoxan and after bulbospinal noradrenaline deafferentation with 6 hydroxydopamine. These results suggest that the increase in MAP induced by i.t. BK is mediated by the sympathoadrenal system while the decrease in HR is ascribable to a vagal reflex involving sensory C-fibers and a spinobulbar pathway. This pharmacological evidence therefore supports a role for kinins in cardiovascular regulation in the spinal cord. PMID- 1601055 TI - Protective effects of amiloride on the ischemic reperfused rat heart. Relation to mitochondrial function. AB - We examined the effect of amiloride on mechanical, electrical and mitochondrial function as well as ultrastructural integrity, in isolated rat hearts subjected to 30 min low-flow ischemia and 30 min reperfusion. In control hearts, ischemia produced a rapid loss of contractility and a concomitant elevation in resting tension which were associated with a 100% incidence in arrhythmic activity. Reperfusion produced a 22 and 54% recovery in force and rate of force (dF/dt) development, respectively. In control hearts the incidence of arrhythmias was 100% within 5 min of reperfusion which then declined to 50% by 30 min. Ultrastructural defects in these hearts were restricted primarily to mitochondrial damage. Amiloride significantly attenuated the elevation in resting tension at the end of ischemia. Postischemic recovery was significantly increased to 38 and 86% for force and dF/dt, respectively and the incidence of arrhythmias was reduced to 30%. No ultrastructural defects were ever observed in amiloride treated reperfused hearts. Both interfibrillar and subsarcolemmal mitochondria exhibited depressed respiratory function and adenine nucleotide translocase activity. Although virtually all parameters tended to be elevated in mitochondria isolated from amiloride-treated hearts, a significant increase was seen in only one case. Our results therefore demonstrate an ability of amiloride to enhance postischemic contractile recovery and reduce the incidence of arrhythmias, particularly during reperfusion, an effect associated with virtual total prevention of ultrastructural defects. Although the salutary effect was not significantly correlated to improved mitochondrial function, this dissociation may have been due to removal of damaged mitochondria during the isolation process, in view of diminished mitochondrial damage as viewed by transmission electron microscopy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601056 TI - Absence of 2-phenylethylamine binding after monoamine oxidase inhibition in rat brain. AB - Earlier work has suggested the existence of saturable and highly specific binding sites for [3H]2-phenylethylamine in rat forebrain membranes. Since monoamine oxidase (MAO) was not inhibited during the assay, the [3H]2-phenylethylamine binding may have been affected by an interaction between 2-phenylethylamine and the enzyme. This is an investigation of [3H]2-phenylethylamine binding to rat forebrain membranes in the presence of two MAO inhibitors, (-)-deprenyl and pargyline. The results show that the high affinity specific binding of [3H]2 phenylethylamine to rat forebrain membranes is inhibited by pretreatment of the membrane with the MAO inhibitors and in vivo injection of the MAO inhibitors in a concentration-dependent manner. In the presence of higher concentrations of MAO inhibitors, the specific binding of [3H]2-phenylethylamine is completely blocked, suggesting that the binding sites reported earlier represent binding to MAO-B. PMID- 1601057 TI - Possible involvement of cholinergic and glycinergic amacrine cells in the inhibition exerted by the ON retinal channel on the OFF retinal channel. AB - In the frog retina, the inhibition exerted by the ON channel on the OFF channel was evidenced by the increase in transient ganglion cell OFF responses, when the ON channel was blocked by 2-amino-4-phosphonobutyrate (APB). Intraocular administration of the neurotoxic choline analog ethylcholine mustard arizidinium ion (ECMA) also provoked an increase in the number of spikes of transient ganglion cell OFF responses, without suppressing the ON responses. APB, when administrated after ECMA, abolished the ON responses, but did not modify the OFF responses already increased by ECMA. Neurons located in the inner part of the inner nuclear layer were histologically altered by the toxin, and choline acetyltransferase activity was significantly depressed in ECMA-treated retinas. A double immunostaining experiment showed that amacrine cells containing glycine bear muscarinic binding sites. These results confirm the participation of cholinergic neurons in the inhibition exerted by the ON retinal channel on the OFF retinal channel, and suggest the involvement of a cholinergic/glycinergic loop of amacrine cells in this mechanism. PMID- 1601058 TI - 5-HT1A receptors activate a potassium conductance in rat ventromedial hypothalamic neurones. AB - The extracellularly recorded firing rate of rat ventromedial hypothalamic neurones in vitro was inhibited by 5-hydroxytryptamine (5-HT), 5 carboxamidotryptamine (5-CT), 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and buspirone, 2-methyl-5-HT was relatively ineffective. At 1 microM, spiperone and cyanopindolol antagonised the 5-CT induced inhibition, MDL 72222 (10 microM) and ketanserin (1 microM) did not. Intracellular recordings with voltage-clamp revealed that 5-HT and 5-CT evoked a tetrodotoxin-resistant outward current with a reversal potential of ca. -100 mV. 5-HT1A receptors likely activate a potassium conductance on these neurones. PMID- 1601059 TI - The gastric antisecretory action of lipopolysaccharide is blocked by indomethacin. AB - We have recently found that bacterial lipopolysaccharide (LPS) at minute doses inhibits the secretion of gastric acid and pepsin in rats. The present study was performed to examine the mechanism by which LPS exerts its antisecretory action. The i.p. injection of LPS resulted in a dose-dependent (40-4000 ng/kg) decrease in gastric acid output in pylorus-ligated rats. However, preinjection of indomethacin (2-10 mg/kg s.c.), an inhibitor of prostaglandin biosynthesis, prevented the LPS-induced inhibition of gastric secretion in a dose-related manner, while these concentrations of indomethacin by themselves did not affect gastric acid output. These results suggest that LPS requires an intact prostaglandin system to exhibit its inhibitory action on gastric secretion. PMID- 1601060 TI - Enhanced vasodilatory responses to bradykinin in stroke-prone spontaneously hypertensive rats. AB - Vasodilatory responses to bradykinin (BK) and acetylcholine (ACh) were compared in phenylephrine preconstricted perfused kidneys from 30-week-old male stroke prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Responses to ACh did not differ between kidneys from SHRSP and WHY. BK induced dilatation was greater in kidneys from SHRSP relative to WHY and was not affected by indomethacin or captopril. These results indicate that renal vasodilatory responsiveness to bradykinin is enhanced in SHRSP with established hypertension. PMID- 1601061 TI - Vascular protein kinase C in Wistar-Kyoto and spontaneously hypertensive rats. AB - Phorbol esters which activate protein kinase C (PKC) produced concentration related force development in aorta from spontaneously hypertensive rat (SHR) and Wistar-Kyoto rat (WKY); all were 2-7 x more potent in SHR. However, total PKC activity in aortas, as well as carotid, caudal and renal arteries, was not different, when SHR was compared with WKY. Binding of phorbol dibutyrate to particulate aortic PKC was similar in SHR and WKY (same apparent Kd and Bmax values), as was potency for displacement of phorbol dibutyrate by phorbol myristate acetate. Furthermore, there was no difference in potency with staurosporine, H-7, and calmidazolium in inhibiting SHR and WKY aortic PKC. These data demonstrate enhanced contractile sensitivity to PKC-activating phorbol esters in SHR aortic smooth muscle that is not related to activity, phorbol ester binding, or sensitivity to inhibitors when SHR PKC is compared with WKY PKC. Thus, signal transduction events distal to PKC activation may be responsible for enhanced vascular contractile sensitivity to phorbol esters in SHR. PMID- 1601062 TI - Effect of N omega-nitro-L-arginine methyl ester on arterial pressure and on vasodilator and vasoconstrictor responses: influence of initial vascular tone. AB - Intravenous N omega-nitro-L-arginine methyl ester (L-NAME) 0.3, 3 and 30 mg/kg produced a dose-dependent increase of blood pressure in urethane-anesthetized rats. Similar pressure responses occurred in rats after ganglionic or adrenergic blockade, hemorrhage or acetylcholine infusion. L-NAME potentiated the pressor response to phenylephrine in pentolinium-treated rats. L-NAME increased the depressor effect of acetylcholine and sodium nitroprusside and shortened the acetylcholine response. Phenylephrine potentiated the magnitude but not the duration of the acetylcholine response and had no effect on the duration or magnitude of sodium nitroprusside-induced hypotension. L-NAME potentiated the initial fall of blood pressure induced by a 5 min acetylcholine infusion but had no effect on the pressure drop at the end of infusion. These results suggest that basal production of nitric oxide (NO) is not related to vascular tone and do not support the view that acetylcholine releases NO from resistance vessels in vivo. PMID- 1601063 TI - Rotational behavior as a classically conditioned response to pentobarbital administration. AB - Pentobarbital stimulus control of rotational behavior was investigated in rats with unilateral 6-hydroxydopamine lesions of substantia nigra. In conditioning trials, lesioned rats were injected simultaneously with 10 mg/kg pentobarbital and 0.05 mg/kg apomorphine and their rotational (circling) behavior observed and counted. Subsequent to three consecutive daily conditioning sessions, animals were re-introduced to the rotation environment and tested with saline or pentobarbital. Pentobarbital, but not saline, administration was followed by a brief epoch of rapid contralateral rotation. After additional conditioning trials in which pentobarbital and apomorphine administration were paired, test sessions with 1 g/kg ethanol and with 10 mg/kg chlordiazepoxide were conducted. Most animals did not rotate in response to ethanol administration and most did rotate in response to chlordiazepoxide. Finally, in order to determine the persistence of the conditioned effect, animals were tested with pentobarbital 15 weeks after their last conditioning session and were found to rotate actively in response. PMID- 1601064 TI - Benzimidazolone derivatives act as 5-HT4 receptor ligands in rat oesophagus. AB - Three benzimidazolone derivatives have been evaluated in the tunica muscularis mucosae preparation of the rat oesophagus for activity at the 5-HT4 receptor. BIMU 1 (endo-N-(8-methyl-8-azabicyclo-[3.2.1]oct-3-yl)-2,3-dihydro-3-ethyl-2-ox o 1H-benzimidazole-1-carboxamide HCl) and BIMU 8 (endo-N-(8-methyl-8 azabicyclo[3.2.1]oct-3-yl)-2,3-dihydro-(1-methyl)eth yl- 2-oxo-1H-benzimidazole-1 carboxamide HCl) acted as potent but partial agonists relative to 5-HT whereas DAU 6215 (N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)2,3-dihydro-2-oxo-1H- benzimidazole-1-carboxamide HCl) behaved as a competitive antagonist with a pA2 of 6.5. The pEC50 values for BIMU 1 and BIMU 8 were 8.0 and 7.9, respectively, compared with 8.2 for 5-HT. Intrinsic activity values were 0.7 and 0.9, respectively. BIMU 1 and BIMU 8 are the most potent synthetic agonists so far tested in rat oesophagus, and DAU 6215 exhibits an equivalent affinity to ICS 205 930 at the 5-HT4 receptor. PMID- 1601065 TI - The calcium channel antagonist, flunarizine, protects against ventricular fibrillation. AB - Elevations in intracellular calcium during myocardial ischemia have been implicated in the development of lethal cardiac arrhythmias. The calcium antagonist, flunarizine, has been shown to suppress the accumulation of intracellular calcium and has been proposed to protect against triggered activity due to calcium overload. Using 13 mongrel dogs with healed myocardial infarctions, ventricular fibrillation (VF) was induced by a 2 min coronary occlusion during exercise. This exercise plus ischemia test consistently induced VF during control (C, vehicle) presentations. Pretreatment with flunarizine (2.5 mg/kg i.v.) completely suppressed VF in all the animals (P less than 0.001 Chi squared). Flunarizine (F) elicited significant (P less than 0.01 ANOVA) reductions in left ventricular (LV) systolic pressure (C 143.2 +/- 12.0 F 92.3 +/ 10.5 mm Hg), LVdP/dt max (C 4256 +/- 251.9, F 1784 +/- 297.2 mm Hg/s) and heart rate (C 118.8 +/- 7.4, F 104.7 +/- 9.0 beats/min). Since heart rate can contribute significantly to the development of VF, the exercise plus ischemia test was repeated with heart rate held constant with ventricular pacing (n = 3, 230.0 +/- 10 beats/min). Flunarizine pretreatment still prevented VF under these conditions. PMID- 1601066 TI - The selective 5-HT2 receptor antagonist amperozide attenuates 1-(2,5-dimethoxy-4 iodophenyl)-2-aminopropane-induced inhibition of male rat sexual behavior. AB - This study was aimed at exploring the role of 5-HT2/5-HT1C neurotransmission in male rat sexual behavior. The administration of the 5-HT2/5-HT1C agonist, 1-(2,5 dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (1 mg/kg), suppressed sexual activity in most of the animals. The suppressive effect of DOI was antagonized by treatment with amperozide, a selective 5-HT2 receptor antagonist, in doses which did not by themselves affect sexual activity. In addition, several other serotonin antagonists were tested with varying affinity profiles for 5-HT2/5-HT1C receptors, including ketanserin, ritanserin, and mesulergine. All these compounds antagonized the suppressive action of DOI. In contrast, no antagonizing effect was obtained by treatment with (-)-alprenolol, a 5-HT1A antagonist. The present findings suggest that 5-HT2/5-HT1C receptors might be involved in the neural control of male rat sexual behavior, presumably by exerting an inhibitory influence on the behavior. PMID- 1601067 TI - Ganglionic nicotinic receptor agonists exhibit anti-muscarinic effects in guinea pig olfactory cortical brain slices. AB - The action of some nicotinic acetylcholine receptor agonists was re-examined on the surface field potentials (N-waves) evoked by electrical stimulation of the lateral olfactory tract in guinea-pig olfactory cortical brain slices. Bath superfusion of nicotine or the nicotinic stimulants dimethylphenylpiperazinium (DMPP), lobeline, cytisine, tetramethylammonium or suberyldicholine (up to 100 microM) had little or no effect on the extracellular N-wave amplitude, or the membrane potential, input resistance or excitability of olfactory neurones recorded intracellularly. In contrast, the muscarinic agonists, carbachol or oxotremorine-M consistently depressed the field in a reversible dose-dependent manner. Interestingly, in the presence of the ganglionic stimulants DMPP (n = 6 slices) or lobeline (n = 5 slices) (10-50 microM), the effects of carbachol or oxotremorine-M were antagonized in a weak competitive-type manner (pA2 values = 5.58 and 5.63 respectively, estimated from Schild plots, constrained to unity slope). This anti-muscarinic action was unaffected by d-tubocurarine or hexamethonium. Nicotine, cytisine, tetramethylammonium and suberyldicholine showed much weaker and inconsistent carbachol-blocking effects. Combination of DMPP with atropine produced dose ratio shifts close to those predicted for a common-site interaction of two competitive antagonists. In conclusion, consistent pre- or postsynaptic nicotinic agonist actions could not be detected in olfactory cortex slices; however, some ganglionic nicotinic agonists were shown to exhibit significant anti-muscarinic effects on this preparation. We suggest this action might be due to a direct atropine-like mechanism. PMID- 1601068 TI - Propranolol reduces rat dopamine-beta-hydroxylase activity and catecholamine levels. AB - Propranolol treatment (1 mg/kg i.p. twice daily for 8 days) reduced atrial dopamine-beta-hydroxylase (D beta H) activity by 60.5% and lung D beta H activity by 53.5% but did not alter ventricle D beta H activity. Propranolol also significantly reduced atrial noradrenaline (NA) by 66.3%, adrenaline (A) by 40%, dopamine (DA) by 72.4% and lung NA by 46.6% but did not change plasma or cardiac ventricle catecholamines. The addition of propranolol (10(-6) M) to cardiac and lung tissue homogenates in vitro did not inhibit tissue D beta H activities. The results suggest that chronic propranolol treatment inhibits NA synthesis and support the hypothesis of a centrally induced inhibition of sympathetic activity caused by beta-adrenoceptor blockade. PMID- 1601069 TI - Interactions between ibogaine and cocaine in rats: in vivo microdialysis and motor behavior. AB - To investigate a possible basis for the proposed anti-addictive property of ibogaine, the effects of an ibogaine (40 mg/kg i.p.) pretreatment on in vivo neurochemical and motor effects induced by cocaine (20 mg/kg i.p.) were studied. Ibogaine, administered 19 h earlier, potentiated the increase in extracellular dopamine levels in striatum and nucleus accumbens as well as the stimulated motor activity induced by cocaine. Although high doses of cocaine can become aversive by producing an anxiogenic reaction, it is unknown whether the potentiation of cocaine's effects by ibogaine would also cause aversion and lead to a decrease in cocaine addiction. PMID- 1601070 TI - Felbamate reduces hypoxic-ischemic brain damage in vivo. AB - The neuroprotective effects of felbamate were tested in a model of incomplete cerebral ischemia and hypoxia in 7-day-old rat pups. Felbamate pretreatment (300 mg/kg) reduced the surface of infarcted cortex following bilateral carotid ligation, by 42-49% compared to saline and dimethylsulfoxide (DMSO) controls, respectively. The number of necrotic neurons in the dentate gyrus was reduced by 77% over both DMSO controls and saline controls. These results suggest that felbamate deserves further evaluation for its therapeutic potential in hypoxia ischemia. PMID- 1601071 TI - Role of 5-HT receptors in the effect of d-fenfluramine on feeding patterns in the rat. AB - The effect of d-fenfluramine, 1.5 mg/kg i.p., on meal patterns was studied in rats treated i.p. with 1 mg/kg metergoline or 0.5 mg/kg ritanserin or s.c. with 3 mg/kg (+/-)cyanopindolol. d-Fenfluramine significantly reduced eating rate, meal size and total intake in the first 4 h of testing and the effects were antagonized by metergoline. (+/-)Cyanopindolol reduced total intake and the effect of d-fenfluramine on this measure; the effect of d-fenfluramine on meal size (but not on eating rate) was also reduced by (+/-)cyanopindolol. Ritanserin only reduced the rate of eating and the effect of d-fenfluramine on this measure. The results suggest that 5-HT1 receptors, possibly of the 5-HT1B type, are involved in the ability of d-fenfluramine to cause satiety in freely feeding rats. PMID- 1601072 TI - Chronic cocaine alters limbic extracellular dopamine. Neurochemical basis for addiction. AB - The extracellular concentration of dopamine in the ventral striatum was measured daily by means of brain microdialysis. Chronic cocaine (10 mg/kg twice daily) altered the dopamine output compared to that in vehicle-injected rats, inducing a pronounced increase in the first 3 days followed by a clear-cut decrease. This reduction in the output of dopamine during chronic cocaine as well as during withdrawal may be neurochemical substrate for the addictive properties of cocaine. PMID- 1601073 TI - Persistence of contamination of hens' egg albumen in vitro with Salmonella serotypes. AB - A study was made of the persistence of different Salmonella serotypes in hens' egg albumin in vitro at 4, 20 and 30 degrees C. The majority of serotypes remained viable but did not increase in numbers at 20 and 30 degrees C for 42 days. At 4 degrees C many of the serotypes died out. The addition of ferric ammonium citrate on the 42nd day of incubation induced multiplication of organisms incubated at 20 and 30 degrees C, but not at 4 degrees C. The pH and glucose concentration of the albumen diminished only when heavy growth occurred. Salmonella enteritidis remained viable on the air cell membrane in vitro for 17 days at 4, 20 and 30 degrees C. Thirty percent of the organisms also remained motile in albumen for 42 days at 25 degrees C and up to 5% of the cells remained motile for up to 20 days at 4 degrees C. PMID- 1601074 TI - Legionellae isolated from clinical and environmental samples in Spain (1983-90): monoclonal typing of Legionella pneumophila serogroup 1 isolates. AB - Legionella isolates recovered in 21 different Spanish provinces over 8 years from both clinical (67 isolates) and environmental (181) samples, mostly from case associated buildings, are described; 92.5% of clinical isolates were L. pneumophila serogroup 1 (SG1), only five isolates belonging to other species or serogroups: two L. pneumophila SG6, two SG8 and one L. bozemanii SG1 not clearly related with clinical infection. L. pneumophila SG1 accounted for 53.6% of isolates from the environment, followed by SG8 (27.6%), SG3 (9.4%) and SG6 (7.2%). Three isolates were labelled as SG8/10. Subtyping of L. pneumophila SG1 by the standardized panel of monoclonal antibodies revealed 90.3% of clinical and 78.3% of environmental isolates as belonging to Pontiac subgroup. Pontiac isolates were further divided into 55.3% Philadelphia 1 or Allentown 1, 21.9% Benidorm 030E and 20.4% Knoxville 1. Characterization of samples from four outbreaks in which both clinical and environmental isolates had been recovered permitted the recognition of three Philadelphia 1 or Allentown 1 and one Knoxville 1 strains as the aetiological agents. PMID- 1601075 TI - Extended phage-typing scheme for Campylobacter jejuni and Campylobacter coli. AB - The extended phage-typing scheme described for Campylobacter jejuni and Campylobacter coli has established 46 different phage types using 19 typing phages. Altogether 754 campylobacter isolates, 672 C. jejuni and 82 C. coli, isolated from human and non-human sources received from 17 different countries were phage-typed. Overall, 80.6% of the total isolates were typable. Among typable strains, 9 phage types (3, 5, 10, 11, 18, 19, 23, 26 and 44) represented 57.0% of the strains, 21.3% of the strains belonged to another 37 phage types and the remaining 2.3% of isolates were designated atypical. The most common phage type 11 (140/754) was frequently observed among C. jejuni isolates from human (113/561) and non-human sources (18/111), whereas type 44 was frequent among C. coli isolates from human (22/59) and from non-human sources (8/23). A study of the animal host-associations of common phage types showed that contaminated cattle and poultry appear to be the most common sources of human infection. The greatest variety of phage types was observed in Canada (24 phage types), followed by Portugal (17 types) and the UK (14 types), reflecting the larger sample sizes from these countries. Phage type 11 was encountered in 12 different countries and prevalence of other phage types varied from one country to another. The number of isolates typable with the scheme varied from 93.2% (261/280) in Canada to 61% (47/77) in Thailand. However, the number and diversity of phage types makes phage typing the method of choice in epidemiological studies of campylobacter infections. PMID- 1601076 TI - Distribution and characteristics of verocytotoxigenic Escherichia coli isolated from Ontario dairy cattle. AB - Faecal swabs obtained from a random sample of 1131 cows and 659 calves on 100 southern Ontario dairy farms were examined for verocytotoxigenic Escherichia coli (VTEC) using a Vero cell assay. Five isolates from each positive culture were tested similarly. Positive colonies were examined with DNA probes for Shiga-like toxin I (SLT-I) and SLT-II sequences. Probe-negative colonies were tested for neutralization of verocytotoxicity using anti-SLT-I and anti-SLT-IIv antisera. Colonies showing no neutralization response were examined in a polymerase chain reaction procedure. Colonies positive by any test were confirmed to be E. coli biochemically, serotyped, biotyped and tested for antimicrobial resistance. Faecal culture supernatants which were positive in the Vero cell assay, but culture negative, were examined using the neutralization assay. Animals were classified positive by faecal culture supernatant or by positive VTEC isolate. The prevalence rates of VTEC infection in cows and calves were estimated to be 9.5 and 24.7%, respectively. The proportion of animals infected on each farm ranged from 0 to 60% for cows and 0 to 100% for calves. Of 206 VTEC isolates identified, few were of serotypes which have been isolated from humans and none were E. coli O 157.H7. PMID- 1601077 TI - Factors affecting carriage of Neisseria meningitidis among Greek military recruits. AB - Greek military recruits (993) were examined for carriage of meningococci during July 1990. Blood, saliva and throat swab specimens were obtained and each recruit answered a questionnaire providing information on age, education (a measure of socioeconomic level), place of residence, smoking habits and recent infections. The overall carriage rate was 25% but differed between the two camps: 79/432 (18%) in Camp A and 168/561 (30%) in Camp B (P less than 0.0005). In Camp B, there were significantly higher proportions of recruits who were non-secretors (P less than 0.0005), and/or heavy smokers (P less than 0.0005). They were also younger (less than 19 years old) (P less than 0.001), and on the whole had fewer years of education (P less than 0.0005). By univariate analysis, carriage was significantly associated with smoking. By multiple logistic regression analysis, carriage was associated with smoking (P less than 0.001), age (P less than 0.01) and the camp in which the recruits were based (P less than 0.01). Among recruits in Camp B, 15/38 (40%) of those with recent viral infections were carriers compared with 30% for the camp in general. PMID- 1601078 TI - Antibiotic sensitivities of Neisseria meningitidis isolates from patients and carriers in Greece. AB - Usage of antibiotics in southern Europe is less well regulated than in northern countries. The proportion (48%) of meningococci in Spain insensitive to pencillin (MIC greater than or equal to 0.1 mg/l) prompted this investigation of antibiotic sensitivities of isolates from Greek patients with meningitis (31) and carriers (47 school-children and 472 recruits). The agar dilution method was used to determine MIC to penicillin G (PN), sulphamethoxazole (SU), rifampicin (RF), cefaclor (CF) and ciprofloxacin (CP). The proportion of isolates insensitive to PN was 48% for isolates from patients, 19% from school-children and 36.6% from recruits. Resistance to SU (MIC greater than or equal to 16 mg/l) was found in 16% of those from patients, 10.6% from children and 40% from recruits. None of the isolates from patients was resistant to RF (greater than or equal to 1 mg/l) but 6% of those from carriers were. Resistance to CF (greater than or equal to 4 mg/l) was found in 9.2% of patient isolates, 6.4% from children and 23.7% from recruits. All isolates except one were sensitive to CP (MIC range less than 0.0015-0.125 mg/l). Resistances to PN, SU and RF were analysed by serogroup, serotype and subtype of the bacteria. The proportion of resistant isolates showed some variation between different areas of Greece, but it was not statistically significant. PMID- 1601079 TI - Seroepidemiology of Helicobacter pylori infection in vegans and meat-eaters. AB - An enzyme-linked immunosorbent assay has been used to diagnose serologically the prevalence of Helicobacter pylori infection in Asian life-long vegans. There was no difference in the seropositivity between these individuals and a group of age- and sex-matched Asian meat-eaters, indicating the meat consumption is not a risk factor for H. pylori infection. However, both Asian groups had a higher prevalence of infection than age- and sex-matched Caucasian meat-eaters. Additionally, the Asian individuals had a wider range of specific IgG antibody concentrations than the Caucasians. This did not appear to be due to antigenic cross-reactivity between H. pylori and Campylobacter jejuni. The significance of these observations to the establishment of cut-off levels for the serodiagnosis of certain ethnic groups is discussed. PMID- 1601080 TI - Analysis of some virulence factors of Vibrio vulnificus isolated from Rio de Janeiro, Brazil. AB - Twenty strains of V. vulnificus isolated from the environment were investigated for characteristics related to their infectivity such as colonial morphology, enzymatic activity and animal assays. The presence of DNase, chitinase, amylase, lecithinase and gelatinase was observed in 100% of the strains, haemolytic activity was absent, and variable results were obtained in elastase, collagenase and chondroitinase. In the animal assays, 70% of the strains were lethal to adult mice, while 45% caused fluid accumulation in suckling mice. Although all strains had opaque colonies, only 3 of the 20 had the three enzymes elastase, collagenase and gelatinase, and only one of these was virulent in animal assays. PMID- 1601081 TI - A new approach to morbidity risk assessment in hookworm endemic communities. AB - The relationship between paired hookworm prevalence and mean intensity of infection data from geographically defined communities was examined. The results show that, in spite of major socio-economic and environmental differences between communities, the relationship is consistent and non-linear. A generalized value of k (the exponent of the negative binomial distribution) for hookworms was estimated to be 0.34, which is consonant with previous estimates from cross sectional data. Maximum likelihood analysis indicates that the severity of hookworm aggregation in humans has an inverse relationship to mean worm burden which is less marked than for Ascaris lumbricoides. A simple model, based on published estimates of hookworm burdens associated with hookworm anaemia, was used to predict prevalence of morbidity from prevalence of infection data for Tanzania, Kenya and Zambia. Predictions correspond to the observation that hookworm anaemia is highly focal, and largely coastal, in distribution. These analyses suggest that locality-targeting of chemotherapy is particularly appropriate for the control of hookworm morbidity. PMID- 1601082 TI - Bancroftian filariasis in Pondicherry, south India--epidemiological impact of recovery of the vector population. AB - An Integrated Vector Management (IVM) strategy was implemented from 1981 to 1985 in one part of Pondicherry, South India, for the control of the bancroftian filariasis vector Culex quinquefasciatus (the IVM area). The rest of the town (the comparison area) received the conventional larvicidal input. After 1985 both the areas were managed conventionally. The switch to conventional strategy resulted in an increase of vector density in both areas. The microfilaraemia prevalence in humans showed a general decline (P less than 0.05) from 1986 to 1989 only in the IVM area whereas its intensity did not change significantly in either area. While the age-specific rate of gain of infection was generally unchanged in the IVM area, an increase in all age classes was observed after 1985 in the comparison area, where the Annual Transmission Index was high during the previous years. In both areas the rate of loss of infection increased during 1986 9 compared to 1981-6. The results suggest that 3 years is too short a period to relate the changes in entomological parameters to those in the microfilaraemia status of the population. PMID- 1601083 TI - Influenza deaths in Leicestershire during the 1989-90 epidemic: implications for prevention. AB - There is an association between excess winter mortality and epidemics of influenza and it has been suggested that annual influenza vaccination should be offered to all over 65 years old as in the United States. This paper identifies the number of people dying from influenza in Leicestershire UK during the 1989-90 epidemic and the factors associated with a fatal outcome. The findings show that deaths attributed to influenza occur predominantly in very elderly people with underlying ill-health. The risk of influenzal death is greater in residential patients and increases substantially with the number of underlying medical conditions. The estimated death rates in vaccinated and non-vaccinated groups were not significantly different, but there were trends towards protection in both residential and non-residential groups. Influenza vaccine is not reaching the principal target groups and improved methods of influenza control are required. PMID- 1601084 TI - Subacute sclerosing panencephalitis (SSPE) in Papua New Guinea: a high incidence in young children. AB - Eighty-seven cases of subacute sclerosing panencephalitis (SSPE) were diagnosed from September 1988 to April 1991 in Papua New Guinea (PNG), by demonstration of high-titre measles-specific antibodies in cerebrospinal fluid (CSF). For 1990 the annual incidence of SSPE, for the study provinces, was calculated to be 56 cases per million under 20 years of age and it is expected that this figure will be higher in 1991. The mean age of presentation was 4.9 years, with a male to female ratio of 1.8:1. An elevation in the ratio of immunoglobulin G as a percentage of total protein in CSF and an increase in the CSF:serum immunoglobulin G ratio was shown in SSPE patients. The dramatic appearance and high frequency of the disease in PNG might relate to the early age of measles infection encountered in children in this country. PMID- 1601086 TI - International Society for Experimental Hematology, XXIst annual meeting. Providence, Rhode Island, 26-30 July 1992. Abstracts. PMID- 1601085 TI - Isolation of an agent of the spotted fever group rickettsia from tick eggs in Madrid, Spain. AB - Ticks recovered from dogs in rural villages around Madrid (Spain) were processed to isolate rickettsiae. One sample containing mixtures of ticks and four containing eggs, in which rickettsiae had been detected by indirect immunofluorescence with a human serum highly reactive to Rickettsia conorii, were decontaminated, homogenized and inoculated onto Vero cells. Two egg samples yielded a cytopathic agent that reacted positively by immunofluorescence. One sample (14H) was successfully subcultured and identified as a member of the spotted fever group rickettsia. Tick eggs provide suitable material for isolation of rickettsia. PMID- 1601087 TI - Organization of the forelimb area in squirrel monkey motor cortex: representation of digit, wrist, and elbow muscles. AB - The EMG in 8 to 14 hand, forearm, and arm muscles evoked by intracortical electrical stimulation was recorded at 433 sites in layer V in the region of the forelimb area of the primary motor cortex (MI) of three squirrel monkeys during ketamine anesthesia. At each site, the EMG was recorded at movement threshold (T) and at 1.5T and 2T at each site (but less than or equal to 60 microA), and the threshold movement was noted. In the animals examined, the total MI forelimb area identified by movements or EMG occupied about 25 to 35 mm2. At most sites from which a forelimb movement was evoked, EMG activity was evoked in one or more of the recorded muscles. One group of sites located rostrolaterally to the main forelimb area was separated by an intervening zone largely related to the face. The average area from which digit, wrist, elbow, or shoulder movement was evoked at threshold was nearly the same, and their movement thresholds were not significantly different. Average movement thresholds across the anterior posterior extent of MI were also similar. All muscles recorded could be activated by cortical stimulation. Most commonly more than one muscle was activated from a single site. The highest individual EMG levels were produced at sites from which more than one muscle was activated. These results suggest that small regions of MI influence multiple muscles. Individual muscles were typically activated at multiple, spatially separated locations. For many muscles, increasing the stimulation intensity revealed additional separate areas of activation. Spatial locations of different muscles showed considerable interanimal variation. The size of most muscle representations was relatively large. The smallest representations always included the intrinsic hand muscles and the largest included the proximal muscles. Orderly topographic relationships among forelimb joints or muscles within the MI forelimb area were not apparent. Although distal muscle activation tended to be found posteriorly in the forelimb area and proximal muscles tended to be activated from anterior sites, both could be activated from broadly distributed and overlapping areas. The broad, overlapping nature of the muscle representation supports the concept that a small region of cortex is involved in controlling functional groups of muscles. The intermingling of muscle representations may provide a substrate for local cortical interactions among territories representing various muscle synergies or for changing associations of muscle groups. The representation plan derived from these mappings contains elements of all previously described summaries of MI organization.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1601088 TI - Calretinin immunoreactivity in chinchilla and guinea pig vestibular end organs characterizes the calyx unit subpopulation. AB - Immunohistochemical investigations with calretinin, a neuronal calcium binding protein, were made in the vestibular end organs of five guinea pigs and one chinchilla. A specific pattern of immunoreactivity of afferent nerve fibers was found. Immunostaining was restricted to thick fibers innervating the apex of the cristae or the striola of the utricular macula. A study of serial sections revealed that the stained afferents gave rise to calyx endings, but not to collaterals containing bouton endings. The results are consistent with the conclusion that, of the three classes of fibers defined by Fernandez et al. (1988, 1990), only calyx units are calretinin immunoreactive. A count of the number of labelled fibers in the chinchilla crista suggests that the entire population of calyx units is immunoreactive. The conclusion is surprising since the physiology of calyx units does not differ qualitatively from that of other afferents (Baird et al. 1988; Goldberg et al. 1990). The presence of this protein in the calyx neurons may be related to specific post-synaptic functions of this type of afferents. PMID- 1601089 TI - Calcium binding protein (calbindin D28k) immunoreactivity in the hamster superior colliculus: ultrastructure and lack of co-localization with GABA. AB - The expression of specific calcium binding proteins is being used increasingly as a potential neuroanatomical marker for neurons with similar functions. In this study, the distribution of calbindin D28k in the superior colliculus (SC) of adult hamsters was examined by light and electron microscopy. Calbindin immunoreactivity was prominent in specific regions and laminae of the SC throughout its rostrocaudal extent, and was found to label horizontal, vertical and stellate cell types. In addition, calbindin label highlighted "bridges" of neuronal processes in the intermediate layers. The most frequent calbindin immunoreactive profiles seen in the electron microscope were dendrites, some of which were post-synaptic to apparent retinal ganglion cell axon terminals. Labelled axons and axon terminals were less frequently encountered. There was considerable overlap between the size distribution of calbindin D28k immunoreactive neurons and that of GABA-immunoreactive or Nissl stained neurons in the SC. However, using a double fluorescent labelling technique, and examination of the tissue with confocal laser microscopy, no neurons were observed in the hamster SC that showed immunoreactivity for both calbindin and GABA. In this regard, the SC is similar to the mammalian lateral geniculate nucleus and the pretectum, but differs from the neocortex, where calbindin and GABA are colocalized. The demonstration in the SC, as well as other parts of the nervous system, of sub-populations of neurons that contain distinct calcium binding proteins suggests that these neurons have different functional properties. Correlative studies may clarify the relevance of these cytoplasmic components as cell markers, as well as their different patterns of association with neurotransmitters and peptides. PMID- 1601090 TI - Noradrenergic hyperactivity after partial fornix section: role in cholinergic dependent memory performance. AB - Rats with unilateral or bilateral partial section of the fornix were impaired on an eight arm radial maze task. Neurochemical analysis of hippocampal tissue four weeks after the lesions revealed a 50% reduction of choline acetyltransferase (ChAT) activity. The cholinergic marker was correlated negatively with the number of errors in the maze; the lower the ChAT activity, the higher the error score. The fornix lesion also induced a 50% reduction in norepinephrine (NE), but no change in the noradrenergic metabolite methylhydroxyphenylglycol (MHPG), suggesting a net increase in turnover of NE in these animals. Additional lesion of the noradrenergic system with the neurotoxin DSP4 reduced both MHPG and NE levels by more than 90%, compared to nonlesioned controls, and reversed the behavioral deficit. This treatment had no further effect on cholinergic markers. There was a significant negative correlation between ChAT activity and the index of NE turnover, suggesting that hyperactivity in the noradrenergic system after fornix section inhibits the spared cholinergic function and thus exacerbates the cognitive deficit. The pattern of neurochemical results bear a striking resemblance to those seen in some Alzheimer's patients and suggest that an equilibrium among neurotransmitters is important to cognitive function. PMID- 1601091 TI - Inhibitory modulation of the cardiovascular defence response by the ventrolateral periaqueductal grey matter in rats. AB - In rats anaesthetised with alphaxalone/alphadolone, electrical stimulation in the dorsal periaqueductal grey matter (PAG) evoked a pressor response with tachycardia, vasodilatation in the hindlimb and hyperpnoea: a pattern of response known as the defence reaction. Microinjection of the synaptic excitant, D,L homocysteic acid (DLH), but not saline, into the ventrolateral PAG at the level of the decussation of the superior cerebellar peduncle (approximately 7.3-8.3 mm caudal to bregma) produced a reduction in the size of the cardiovascular components of the defence reaction evoked by electrical stimulation in the dorsal PAG. Injections of DLH made outside this region had no effect on the defence response. Injection of DLH into the "defence inhibition area" had no effect on the pressor response evoked distally in the efferent pathway for the defence reaction, by electrical stimulation in the rostral ventrolateral medulla (RVLM). Activation of neurones in a restricted portion of the caudal ventrolateral PAG appears to modulate activity in the descending pathway for the defence response evoked from the dorsal PAG. It is argued that the inhibitory interaction probably occurs at the level of synapses in the RVLM. PMID- 1601092 TI - Short latency cutaneous reflex responses of gamma-efferents in the decerebrate cat. AB - The effect of single shock stimulation, up to 20 x threshold (T), of the sural nerve on the discharges of triceps surae gamma-efferents was investigated in decerebrate cats. Units were classified as static (12) or dynamic (7) on the basis of their resting discharge rates (Murphy et al. 1984). All neurones were excited at short latency by sural nerve stimulation and response size was graded with stimulus intensity. Short latency mixed or inhibitory responses were not evident. Although reflex effects first occurred at low stimulus strengths (less than or equal to 1.5T) in both types of efferent, most responses appeared at higher intensities (greater than 1.5T). The estimated central delays of the responses of static (3.0 +/- 1.1 ms, mean +/- SD) and dynamic (3.4 +/- 1.0 ms) gamma-motoneurones were not significantly different and are consistent with spinal oligosynaptic pathways. The present results differ from those of the only previous study (Johansson and Sojka 1985) of the short latency responses of triceps surae static and dynamic gamma-motoneurones to sural nerve stimulation, in which mixed and inhibitory effects were common in anaesthetised cats. Although differences in recording techniques and gamma sampling may account for the apparent disparity between these studies, it is also feasible that a difference in the setting of interneuronal pathways in the two types of preparation is responsible. The results are discussed in relation to the control of gamma motoneurones with particular reference to the "final common input" hypothesis (Johansson 1981; Appelberg et al. 1983). PMID- 1601093 TI - Coordination of the legs of a slow-walking cat. AB - On the basis of behavioural studies the influences that coordinate the movement of the legs of a slowly walking cat have been investigated. The recording method applied here allows for the measurement of forward and backward movement of the legs which are called swing and stance movements, respectively. Influences between contralateral legs, i.e. both front legs or both hind legs, are stronger than those occurring between ipsilateral legs, i.e. front and hind leg of the same side. Influences which coordinate the front legs seem to be of the same kind as those for the hind legs. These influences are symmetrical, which means that the same type of influence acts from right to left leg and in the reverse direction. Two types of influences are described for contralateral legs: 1. When the influencing leg performs a swing movement, the influenced leg is prevented from starting a swing movement. 2. When the influencing leg performs a stance movement, the probability that the influenced leg starts a swing movement increases as the influencing leg moves backwards during its stance movement. In contrast to contralateral coupling, the ipsilateral influences are symmetric, i.e. a different influence acts from front to hind leg than does in the reverse direction. The front leg is influenced to start a swing when both legs have approached each other to a given value. The hind leg is influenced to start a stance movement after the front leg has begun its swing. PMID- 1601094 TI - The effects of lighting conditions on responses of cells selective for face views in the macaque temporal cortex. AB - Neural mechanisms underlying recognition of objects must overcome the changes in an object's appearance caused by inconsistent viewing conditions, particularly those that occur with changes in lighting. In humans, lesions to the posterior visual association cortex can impair the ability to recognize objects and faces across different lighting conditions. Inferotemporal lesions in monkey have been shown to produce a similar difficulty in object matching tasks. Here we report on the extent to which cell responses selective for the face and other views of the head in monkey temporal cortex tolerate changes in lighting. For each cell studied the (preferred) head view eliciting maximal response was first established under normal lighting. Cells were then tested with the preferred head view lit from different directions (i.e. front, above, below or from the side). Responses of some cells failed to show complete generalization across all lighting conditions but together as a "population" they responded equally strongly under all four lighting conditions. Further tests on sub-groups of cells revealed that stimulus selectivity was maintained despite unusual lighting. The cells discriminated between head and control stimuli and between different views of the head independent of the lighting direction. The results indicate that constancy of recognition across different lighting conditions is apparent in the responses of single cells in the temporal cortex. Lighting constancy appears to be established by matching the retinal image to view-specific descriptions of objects (i.e. neurons which compute object structure from a limited range of perspective views). PMID- 1601095 TI - Feedforward stabilization in a bimanual unloading task. AB - When one hand removes a load from the other hand, feedforward motor commands stabilize the position of the unloaded hand. We studied the stabilization of the postural hand using a novel apparatus that allowed unloading at different rates, and unexpected uncoupling of the unloading force from the postural hand. Feedforward stabilization of hand position was observed in all subjects. This stabilization was achieved both by deactivation of postural agonist muscles and by activation of postural antagonist muscles. The neural feedforward command apparently increased with unloading rate. However, the command only partially canceled the interaction torque generated by removing the load, and stabilization became less effective as unloading rate increased. PMID- 1601096 TI - Somatosensory control of precision grip during unpredictable pulling loads. I. Changes in load force amplitude. AB - In manipulating 'passive' objects, for which the physical properties are stable and therefore predictable, information essential for the adaptation of the motor output to the properties of the current object is principally based on 'anticipatory parameter control' using sensorimotor memories, i.e., an internal representation of the object's properties based on previous manipulative experiences. Somatosensory afferent signals only intervene intermittently according to an 'event driven' control policy. The present study is the first in a series concerning the control of precision grip when manipulating 'active' objects that exert unpredictable forces which cannot be adequately represented in a sensorimotor memory. Consequently, the manipulation may be more reliant on a moment-to-moment sensory control. Subjects who were prevented from seeing the hand used the precision grip to restrain a manipulandum with two parallel grip surfaces attached to a force motor which produced distally directed (pulling) loads tangential to the finger tips. The trapezoidal load profiles consisted of a loading phase (4 N/s), plateau phase and an unloading phase (4 N/s) returning the load force to zero. Three force amplitudes were delivered in an unpredictable sequence; 1 N, 2 N and 4 N. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N), were superimposed on various background loads. The movement of the manipulandum, the load forces and grip forces (normal to the grip surfaces) were recorded at each finger. The grip force automatically changed with the load force during the loading and unloading phases. However, the grip responses were initiated after a brief delay. The response to the loading phase was characterized by an initial fast force increase termed the 'catch-up' response, which apparently compensated for the response delay--the grip force adequately matched the current load demands by the end of the catch-up response. In ramps with longer lasting loading phases (amplitude greater than or equal to 2 N) the catch-up response was followed by a 'tracking' response, during which the grip force increased in parallel with load force and maintained an approximately constant force ratio that prevented frictional slips. The grip force during the hold phase was linearly related to the load force, with an intercept close to the grip force used prior to the loading. Likewise, the grip force responses evoked by the fast loadings superimposed on existing loads followed the same linear relationship.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1601097 TI - Somatosensory control of precision grip during unpredictable pulling loads. II. Changes in load force rate. AB - In the previous paper regarding the somatosensory control of the human precision grip, we concluded that the elicited automatic grip force adjustments are graded by the amplitude of the imposed loads when restraining an 'active' object subjected to unpredictable pulling forces (Johansson et al. 1992a). Using the same subjects and apparatus, the present study examines the capacity to respond to imposed load forces applied at various rates. Grip and load forces (forces normal and tangential to the grip surfaces) and the position of the object in the pulling direction (distal) were recorded. Trapezoidal load force profiles with plateau amplitudes of 2 N were delivered at the following rates of loading and unloading in an unpredictable sequence: 2 N/s, 4 N/s or 8 N/s. In addition, trials with higher load rate (32 N/s) at a low amplitude (0.7 N) were intermingled. The latencies between the start of the loading and the onset of the grip force response increased with decreasing load force rate. They were 80 +/- 9 ms, 108 +/- 13 ms, 138 +/- 27 ms and 174 +/- 39 ms for the 32, 8, 4 and 2 N/s rates, respectively. These data suggested that the grip response was elicited after a given minimum latency once a load amplitude threshold was exceeded. The amplitude of the initial rapid increase of grip force (i.e., the 'catch-up' response) was scaled by the rate of the load force, whereas its time course was similar for all load rates. This response was thus elicited as a unit, but its amplitude was graded by afferent information about the load rate arising very early during the loading. The scaling of the catch-up response was purposeful since it facilitated a rapid reconciliation of the ratio between the grip and load force to prevent slips. In that sense it apparently also compensated for the varying delays between the loading phase and the resultant grip force responses. However, modification of the catch-up response may occur during its course when the loading rate is altered prior to the grip force response or very early during the catch-up response itself. Hence, afferent information may be utilized continuously in updating the response although its motor expression may be confined to certain time contingencies. Moreover, this updating may take place after an extremely short latency (45-50 ms).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1601098 TI - Somatosensory control of precision grip during unpredictable pulling loads. III. Impairments during digital anesthesia. AB - During manipulation involving restraint of 'active' (mechanically unpredictable) objects, it is presumed that the control of the grip and other reaction forces more regularly relies on somatosensory input than during manipulation of 'passive' (mechanically predictable) objects. In companion studies we have shown that grip forces are automatically adjusted to the amplitude and the rate of distal pulling loads imposed through an 'active' object held in a precision grip. In this study anesthesia of either one or both digits holding the manipulandum was used to examine whether the grip force regulation was dependent on afferent signals from the digits. Five types of trapezoidal load force profiles of various rate and amplitude combinations were given in an unpredictable sequence while the subject was prevented from seeing the hand. Grip forces, load forces and position of the manipulandum in the pulling direction were recorded. With both digits anesthetized the load amplitude changes yielded considerably less grip force modulation and in many trials obvious grip force responses were absent. Moreover, the latencies between the onset of the load changes and the observed grip force responses were much prolonged. However, there was pronounced inter-individual variation. Subjects exhibiting a lower stiffness in the pulling direction, probably due to more flexed fingers when holding the manipulandum, showed a higher force modulation, higher responsiveness to the load ramps and shorter latencies. Hence, under certain conditions afferent input from receptors proximal to the digits could be utilized to provide some grip regulation. The evoked grip force responses showed an initial response similar to the normally occurring 'catch-up' response, but it was not graded by the load force rate. Also, there was no 'tracking' response, suggesting that the latter was contingent upon a moment-to-moment control using afferent input from the digits. With only one digit anesthetized (thumb) the handicap was less severe. Thus, the grip force regulation was impaired under any condition of digital anesthesia, i.e., afferent input from both index finger and thumb was required for the adequate operation of the grip force regulation. PMID- 1601099 TI - Dead zone for express saccades. AB - The saccadic eye movements of three humans and one non-human primate (a male rhesus monkey) have been measured for target eccentricities between 0.3 and 15 deg. With a gap task (fixation point offset precedes target onset by 200 ms) and a target at 4 deg, all subjects produced reasonable amounts of express saccades as indicated by a clear peak in the distribution of their saccadic reaction times (SRT): about 100 ms in human subjects and 70 ms in the monkey. This peak disappeared with decreasing target eccentricity below 2 deg, but saccades of longer (regular) reaction times were still present. Thus it was found that there exists a dead zone for express saccades. In addition, small saccades have a much stronger tendency to overshoot the target and their velocity falls above the main sequence as defined by the least square fit of an exponential v = vo(1-exp( a/ao)) to the maximal velocity (v) versus amplitude (a) relationship (vo and ao are constants fitted). It is concluded that for small saccades the express way is blocked functionally or does not exist anatomically. PMID- 1601100 TI - The role of predictive visual temporal information in the coordination of muscle activity in catching. AB - This study addresses the question as to the nature of the information on which the preactivation of the appropriate muscles in the grasping of the ball in a one handed catching task is initiated and coordinated. High speed film and electromyograms were recorded while experiences subjects (N = 4) caught balls- projected towards them by a ball-machine at different speeds (11.9, 13.9 and 16.2 m/s--resulting in significantly different flight times of 508, 443 and 355 ms, respectively). Tau-margins (times to contact) values were calculated at the time of the initiation of the grasp movement for each subject at each speed. No significant differences were found between tau-margins at different speeds. Further, the onset of the muscle activity for the initiation of the grasp movement was shown to be independent of ball speed. These findings lend support to the contention that the initiation of the grasp movement in catching is controlled and coordinated by the optical variable tau which specifies (directly) this time-to-contact. Given that the muscle group selected includes both flexors and extensors, co-activation on the basis of tau information is evidenced. PMID- 1601101 TI - Regulation of bipedal stance: dependency on "load" receptors. AB - According to recent observations, influence of body load has to be taken into account for the neuronal control of upright stance in addition to the systems known to be involved in this regulation (e.g. afferent input from vestibular canals, visual and muscle stretch receptors). The modulation of compensatory leg muscle electromyographic (EMG) responses observed during horizontal body posture indicates the existence of a receptor system which responds to loading of the body against the supporting platform. This receptor should be located within the extensor muscles because a compensatory EMG response and a loading effect on this response was only present following translational, but not rotational impulses. As the EMG responses were identical to those obtained during upright stance, it is argued that these load receptors activate postural reflexes. According to recent observations in the spinal cat, this afferent input probably arises from Golgi tendon organs and represents a newly discovered function of these receptors in the regulation of stance and gait. PMID- 1601102 TI - Differential distribution of 68 Kd and 200 Kd neurofilament proteins in the gerbil hippocampus and their early distributional changes following transient forebrain ischemia. AB - The distribution of neurofilament (NF) proteins was studied immunohistochemically in the gerbil hippocampus with antibodies against NF68 (68 Kd molecular weight) and NF200 proteins, and changes in the distribution of NF proteins after transient ischemia were observed in order to investigate the temporal correlation between NF and delayed neuronal death. In the normal hippocampus, NF68-like immunoreactivity (NF68-LI) was densely distributed in nerve processes in CA2, CA3 and the hilus of the dentate gyrus but was less intense in CA1. In contrast, processes with NF200-LI appeared to be evenly distributed in CA1, CA2, CA3 and the dentate gyrus. Mongolian gerbils were subjected to transient ischemia for 5 min by bilateral carotid occlusion and subjected to immunohistochemistry 1, 2, 3 and 4 days after ischemia. Following transient ischemia, prior to neuronal cell death, the intensity of both NF68-LI and NF200-LI decreased in the whole hippocampal formation. This decrease was more obvious in the case of NF68-LI than NF200-LI. Four days after ischemia, when neuronal death of CA1 pyramidal cells had occurred, processes in CA1, particularly 68 Kd components, showed marked decreases in number and staining intensity, although processes in most layers of CA2, CA3 and the dentate gyrus appeared to be stained similarly to normal brain. Since NF68 protein is considered to be the major component of NF proteins and NF200 is an associated accessory protein, the current observations suggest that the poor distribution of NF68 in CA1 and the early loss of NF proteins may be closely related to selective vulnerability of CA1 pyramidal cells and delayed neuronal death. PMID- 1601103 TI - Ischemic penumbra in a model of reversible middle cerebral artery occlusion in the rat. AB - It has become increasingly clear that a stroke lesion usually consists of a densely ischemic focus and of perifocal areas with better upheld flow rates. At least in rats and cats, some of these perifocal ("penumbral") areas subsequently become recruited in the infarction process. The mechanisms may involve an aberrant cellular calcium metabolism and enhanced production of free radicals. In general, though, the metabolic perturbation in the penumbra requires better characterization. The objective of this article was to define flow distribution in a rat model of reversible middle cerebral artery (MCA) occlusion, so as to allow delineation of the metabolic aberrations responsible for the subsequent infarction. We modified the intraluminal filament occlusion model recently developed by Koizumi et al. (1986), and described in more detail by Nagasawa and Kogure (1989), adopting it for use in both spontaneously breathing and artificially ventilated rats. Successful occlusion of the MCA (achieved in about 9/10 rats) was judged by unilateral EEG depression in ventilated rats, and neurological deficits, such as circling, in spontaneously breathing ones. CBF in the ipsilateral hemisphere was reduced to nearly constant values after 20, 60, and 120 min of occlusion, flow rates in the focus being about 10% and in the perifocal ipsilateral areas about 15-20% of control (contralateral side). When the filament was left in place (permanent occlusion) 2,3,5-triphenyl tetrazolium chloride (TTC) staining and histopathology after 24 h showed a massive infarct on the occluded side, extending from caudoputamen and overlaying cortex to the occipital striate cortex. Animals recirculated after 60 min of MCA occlusion, and allowed to survive 7 days for histopathology, showed infarction of the caudoputamen (lateral part or whole nucleus) in 5/6 animals and selective neuronal necrosis in one animal. The neocortex showed either infarcts, selective neuronal necrosis, or no damage. There was some overlap between neocortical areas which were infarcted and those which were salvaged by reperfusion. In general, though, both the CBF data and the recovery studies with a histopathological endpoint define large parts of the neocortex as perifocal (penumbral) areas which lend themselves to studies of metabolic events leading to infarction. PMID- 1601104 TI - Cerebral blood flow and histopathological changes following permanent bilateral carotid artery ligation in Wistar rats. AB - Cerebral blood flow and histopathological changes after bilateral carotid artery ligation (BCAL) in Wistar rats were studied. Eight of the 38 rats (21%) died within one week. In the 30 survivors, the incidence of histopathological change was 90% in the caudate nucleus, 23% in the cortex, 30% in the hippocampus, and 0% in the other structures. Local cerebral blood flow (LCBF) was measured using the quantitative autoradiographic 14C-iodoantipyrine technique in 24 anatomically discrete regions of the brain. BCAL induced ischemia in the entire forebrain. The percent reduction of LCBF was between 25-94% of the control at 2.5 h after BCAL. LCBF tended to recover 1 week after BCAL except for the regions of neuronal damage. These results suggest that neuronal damage does not correlate with the flow rate. In the present study, selective neuronal damage was also observed in rats with chronic cerebral ischemia. PMID- 1601105 TI - Invertebrate neuropeptides: their localization, structure and function. PMID- 1601106 TI - Neuropeptides of the silkworm, Bombyx mori. AB - Six neuropeptides of the silkworm, Bombyx mori, have been isolated and chemically characterized during the past 10 years. They are bombyxin, prothoracicotropic hormone, pheromone-biosynthesis-activating neuropeptide/melanization-and-reddish coloration hormone, diapause hormone, eclosion hormone, and adipokinetic hormone. Recent progress in research on these neuropeptides is described. PMID- 1601107 TI - Adipokinetic hormones: cell and molecular biology. AB - Adipokinetic hormones AKH I (pGlu-Leu-Asn-Phe-Thr-Pro-Asn-Trp-Gly-Thr-NH2) and AKH II (pGlu-Leu-Asn-Phe-Ser-Trp-Gly-Thr-NH2) are synthesized by neurosecretory cells (NSC) of the corpora cardiaca (CC) in the locust, Schistocerca gregaria. These NSC constitute a homogeneous 'peptide factory' as each cell synthesizes both AKH I and AKH II. This homogeneity makes the CC an excellent system in which to study aspects of neuropeptide biosynthesis. This report summarizes recent findings on AKH inactivation and metabolism, as well as on AKH prohormone processing and biosynthesis. PMID- 1601108 TI - Crustacean neuropeptides: structures, functions and comparative aspects. AB - In this article, an attempt is made to review the presently known, completely identified crustacean neuropeptides with regard to structure, function and distribution. Probably the most important progress has been made in the elucidation of a novel family of large peptides from the X-organ-sinus gland system which includes crustacean hyperglycemic hormone (CHH), putative molt inhibiting hormone (MIH) and vitellogenesis (= gonad)-inhibiting hormone (VIH). These peptides have so far only been found in crustaceans. Renewed interest in the neurohemal pericardial organs has led to the identification of a number of cardioactive/myotropic neuropeptides, some of them unique to crustaceans. Important contributions have been made by immunocytochemical mapping of peptidergic neurons in the nervous system, which has provided evidence for a multiple role of several neuropeptides as neurohormones on the one hand and as local transmitters or modulators on the other. This has been corroborated by physiological studies. The long-known chromatophore-regulating hormones, red pigment concentrating hormone (RPCH) and pigment-dispending hormone (PDH), have been placed in a broader perspective by the demonstration of an additional role as local neuromodulators. The scope of crustacean neuropeptide research has thus been broadened considerably during the last years. PMID- 1601110 TI - Peptidergic co-transmission in Aplysia: functional implications for rhythmic behaviors. AB - Despite their ubiquitous presence in the central and peripheral nervous systems, the behavioral functions of peptide co-transmitters remain to be elucidated. The marine mollusc Aplysia, whose simple nervous system facilitates the study of the neural basis of behavior, was used to investigate the role of peptidergic co transmission in feeding behavior. Several novel modulatory neuropeptides were purified, and localized to identified cholinergic motorneurons. Physiological and biochemical studies demonstrated that these peptides are released when the motorneurons fire at frequencies that occur during normal behavior, and that the peptides modify the relationship between muscle contraction amplitude and relaxation rate so as to maintain optimal motor output when the intensity and frequency of feeding behavior change. PMID- 1601109 TI - Comparative aspects of structure and action of molluscan neuropeptides. AB - A number of neuropeptides were isolated from the ganglia and muscles of molluscs, and their actions were examined. Diverse neuropeptides, in addition to several classical neurotransmitters, were suggested to be involved in the regulation of the anterior byssus retractor muscle of Mytilus. A wide structural variety of members of the Mytilus inhibitory peptide family was observed in each of the genera Mytilus, Achatina and Helix. Gly-Trp-NH2, the C-terminal dipeptide fragment of the neuropeptide AGPWamide, showed a more potent action than the parent peptide in all of the muscles examined. Peptides related to some molluscan neuropeptides were found to be distributed interphyletically. Some neuropeptides containing a D-amino acid residue were found in Achatina and Mytilus. These aspects of molluscan neuropeptides are thought not to be exceptional. PMID- 1601112 TI - Antarctic fishes survive exposure to carbon monoxide. AB - The extensive in vivo conversion of haemoglobin to the carbon monoxide derivative has no discernible effect on the survival of the red-blooded Antarctic fish Pagothenia bernacchii. Analysis of caudally sampled blood of cannulated specimens revealed that reconversion of carbon-monoxy haemoglobin to oxyhaemoglobin was complete within 48 hours. Thus, under stress-free conditions, haemoglobin is not necessary for survival of P. bernacchii. Red-blooded Antarctic fishes can carry oxygen necessary for routine delivery dissolved in plasma, in a similar way to the haemoglobinless Channichthyidae, although they lack the morphological and physiological adaptations which allow the latter to prosper without any haemoglobin. PMID- 1601111 TI - The Light Green Cells of Lymnaea: a neuroendocrine model system for stimulus induced expression of multiple peptide genes in a single cell type. AB - We review recent experiments showing that the cerebral neuroendocrine Light Green Cells (LGCs) of the freshwater snail, Lymnaea stagnalis, express a family of distinct though related molluscan insulin-related peptide (MIP) genes. The LGCs are involved in the regulation of a wide range of interrelated life processes associated with growth, (energy) metabolism and reproduction. We consider the mechanism of generation of diversity among MIPs, and present evidence that conditions with distinct effects on growth, metabolism and reproduction also can induce distinct patterns of expression of the MIP and schistosomin genes. The stimulus-dependent expression of multiple neuropeptide genes enormously increases the adaptive potential of a peptidergic neuron. We suggest that this contributes significantly to the information-handling capacity of the brain. PMID- 1601113 TI - Abnormal lipid composition of microsomes from cirrhotic rat liver--does it contribute to decreased microsomal function? AB - We determined to what extent a change in the lipid composition of the smooth endoplasmic reticulum contributes to altered microsomal function in cirrhosis. Rats were rendered cirrhotic either by chronic exposure to phenobarbital/CCl4 (MCIR) or by bile duct ligation (BCIR). Microsomal function was tested in vivo by the aminopyrine breath test (ABT), then microsomes were prepared and their phospholipid and cholesterol composition analysed. ABT was reduced by 35 and 41% in BCIR and MCIR, respectively. Cholesterol in microsomes was increased in both cirrhotic groups. (BCIR + 154%, MCIR + 75%) while total phospholipid content was not affected. As shown in other membrane systems, the phospholipid/cholesterol (PL/XOL) ratio showed an excellent inverse correlation with fluorescence anisotropy determined by diphenylhexatriene fluorescence polarization (r = 0.896). The PL/XOL ratio was significantly correlated with aminopyrine N demethylation in vivo (r = 0.649). Alterations in the composition of phospholipid groups (an increase in sphingomyelin in both cirrhotic groups, and a decrease in phosphatidylcholine and an increase in phosphatidylethanolamine in BCIR) also contributed to increased membrane rigidity. We conclude that altered membrane fluidity contributes to diminished microsomal function but that other factors must also be involved since the PL/XOL ratio explained only 42% of the variance in aminopyrine N-demethylation. PMID- 1601114 TI - Preferential excretion of glycated albumin in C57BL-Ks-J mice: effects of diabetes. AB - Urinary excretion of glycated albumin was quantitated in genetically hyperglycemic mice (C57BL-Ks-J, db/db mice), a model for non-insulin-dependent diabetes mellitus, and compared with their non-diabetic littermates. The data indicated a preferential excretion of glycated albumin in non-diabetic mice. This phenomenon of 'editing' of glycated albumin is decreased significantly in diabetic mice. Quantitative measurements of overall excretion of glycated albumin suggested that the loss of editing in diabetic mice is due to the dilution of glycated albumin by the unmodified albumin which is excreted in large amounts in diabetic mice. Therefore, the loss of editing observed in this model resembled the one we characterized in insulin-dependent diabetic humans and a streptozotocin-diabetic rat model. PMID- 1601115 TI - Expression of alpha-cardiac myosin heavy chain in mammalian skeletal muscle. AB - We have investigated the reactivity of different human, rat and cat muscles to a monoclonal antibody directed against human alpha-cardiac myosin heavy chain. We have found that special fiber subpopulations of human masseter and extraocular muscles, as well as the bag fibers of human, rat and cat muscle spindles, were reactive to this antibody, indicating that these fibers expressed alpha-cardiac myosin heavy chain or a closely related isoform. This isomyosin was present in the spindle bag fibers at early fetal stages, whereas its expression in masseter and extraocular muscle fibers was not detected during the first 22 weeks of gestation. Our results add to the list of muscle proteins which are expressed in locations or at developmental stages other than those initially described, suggesting that a revision of the present nomenclature of the subgroups of myosin heavy chains might be considered in the future. PMID- 1601116 TI - An agglutinin with unique specificity for N-glycolyl sialic acid residues of thyroglobulin in the hemolymph of a marine crab Scylla serrata (Forskal). AB - A novel agglutinin with specificity for sialic acid sequence of sugars in thyroglobulin is identified in the hemolymph of Scylla serrata. The physico chemical characteristics of its binding affinity, such as pH and temperature optima, and cationic requirements are defined. N-glycolyl neuraminic acid (NeuGc) (at 0.6 mM), in contrast to N-acetyl neuraminic acid (NeuAc) (at greater than 5.0 mM), is the potent inhibitor of hemagglutination. Bovine and porcine thyroglobulins containing NeuGc, inhibited the agglutination. NeuGc-acid glycoprotein fraction (bovine) but not NeuAc-acid glycoprotein fraction (human) inhibited the hemagglutination. The inability of other NeuGc-glycoproteins (bovine submaxillary mucin) to inhibit the agglutination suggests that the agglutinin may also recognize glycosidic linkage associated with NeuGc. The potential of the agglutinin in identifying NeuGc containing human tumor associated antigens is discussed. PMID- 1601117 TI - Sister chromatid exchanges in lymphocytes of normal and alcoholic subjects. AB - The effects of alcohol consumption, cigarette smoking and age on sister chromatid exchange (SCE) frequency in human lymphocytes were assessed by means of multiple linear regression. An increase in SCE rates was associated with alcohol consumption (p = 0.0001), smoking (p = 0.0231), and, to a small extent (p = 0.057), age. These three confounding factors explain 48% of the inter-personal variation in SCE rates among subjects studied. PMID- 1601118 TI - Lipid droplets of neuroepithelial cells are a major calcium storage site during neural tube formation in chick and mouse embryos. AB - In situ precipitation of calcium (Ca2+) with fluoride and antimonate shows that Ca(2+)-specific precipitate is localized almost exclusively within lipid droplets of neuroepithelial cells during neural tube formation in chick and mouse embryos. The density of Ca2+ precipitate within lipid droplets is generally greater in the apical ends of cells situated in regions of the neuroepithelium that are actively engaged in bending. These findings suggest that lipid droplets, in addition to providing a source of metabolic fuel for developing neuroepithelial cells, also serve as Ca(2+)-storage and -releasing sites during neurulation. PMID- 1601119 TI - Does the moon influence the predatory activity of mites? AB - Periodicity in predatory activity was observed in overwintered females of Typhlodromus pyri Scheuten (Acari: Phytoseiidae). Chronobiometrical analysis revealed that an approximately circabiseptan (about-14-day) rhythm is statistically significant, with a striking depression around the full moon. PMID- 1601120 TI - Cortinarins in Cortinarius speciosissimus? A critical revision. PMID- 1601121 TI - Contraceptive failure rates based on the 1988 NSFG. AB - Analysis of data from the 1988 National Survey of Family Growth--corrected for the underreporting of abortion--reveals that contraceptive failure during the first year of use remains a serious problem in the United States, contributing substantially to unintended pregnancy. The pill continues to be the most effective reversible method for which data were available (8% of users accidentally became pregnant during the first year of use), followed by the condom (15%). Periodic abstinence is the method most likely to fail (26%), but accidental pregnancy is also relatively common among women using spermicides (25%). Failure rates vary more by user characteristics such as age, marital status and poverty status than by method, suggesting the extent to which failure results from improper and irregular use rather than from the inherent limitations of the method. PMID- 1601122 TI - Condom slippage and breakage rates. AB - A prospective study using two brands of condoms found that of 405 condoms used for intercourse, 7.9% either broke during intercourse or withdrawal or slipped off during intercourse; none of these events were related to condom brand, past condom use or use of additional lubricant. Of the remaining condoms, 7.2% slipped off during withdrawal; slippage was not related to condom brand or past use of condoms, but it was significantly higher when additional lubricant was used. PMID- 1601123 TI - Reconsidering the IUD. PMID- 1601124 TI - Peer support to keep teenagers alive and well. PMID- 1601125 TI - The terminology of HIV risk. PMID- 1601126 TI - Sexual abuse as a factor in adolescent pregnancy and child maltreatment. AB - Two-thirds of a sample of 535 young women from the state of Washington who became pregnant as adolescents had been sexually abused: Fifty-five percent had been molested, 42 percent had been victims of attempted rape and 44 percent had been raped. Compared with adolescent women who became pregnant but had not been abused, sexually victimized teenagers began intercourse a year earlier, were more likely to have used drugs and alcohol and were less likely to practice contraception. The abused adolescents were also more likely to have been hit, slapped or beaten by a partner and to have exchanged sex for money, drugs or a place to stay. Young women in the abused group were also more likely to report that their own children had been abused or had been taken from them by Child Protective Services. PMID- 1601127 TI - Interchain and intrachain crosslinking of actin thiols by a bifunctional thiol reagent. AB - From 1,9-nonylenedithiol and Ellman's Reagent the bifunctional asymmetric disulfide n-nonylene-1,9-bis-[5-dithio-(2-nitrobenzoic acid)] (NBDN) was prepared. By monovalent reaction with cysteine-374 the crosslinker could be introduced into monomeric actin, with release of one equivalent of yellow 2-nitro 5-thiobenzoate (NTB). From the monovalent actin derivative we prepared a crosslinked actin dimer (Cys-374-Cys-374') as well as a monomer with a crosslink between Cys-374 and Cys-10. Neither crosslinked actin species was able to polymerize the crosslinked monomer even in the presence of phalloidin. The crosslinked monomer polymerized on the addition of dithiothreitol, thus providing the first unpolymerizable actin species whose polymerizability can be restored under mild conditions. We suggest the use of NBDN as a thiol-specific crosslinker that reacts under spectrophotometric control and can be removed by the addition of thiols. PMID- 1601128 TI - Pregnancy hormones, estrogen and progesterone, prevent HIV-1 synthesis in monocytes but not in lymphocytes. AB - Increase in levels of estrogen and progesterone during pregnancy may affect intra uterine HIV-1 infection through their effect on maternal immunocompetent cells. These hormones were examined for containing HIV-1 production from ACH-2 lymphocytes and U1 monocytes. Neither of the hormones has an effect on ACH-2, but with U1, the physiological concentrations (0.1 microgram 0.1 ng) of progesterone and estrogen demonstrate significant inhibition of HIV-1 release. Except for the highest dose of 1 microgram/ml, the dose-response to progesterone and estrogen was not correlated with the negative influence on proliferation of both types of cells. The results suggest that in vivo low doses of female steroids may display specific antiviral activity in monocytes but not in lymphocytes. PMID- 1601129 TI - Phosphorylation sequences in h-caldesmon from phorbol ester-stimulated canine aortas. AB - The high molecular weight form of caldesmon (h-caldesmon) is phosphorylated in vascular smooth muscle. The stoichiometry of caldesmon phosphorylation increases in response to stimulation of the muscle by several contractile agonists; however, the responsible kinase has not been identified. In this study, we have sequenced the phosphopeptides prepared from h-caldesmon phosphorylated in vitro by protein kinase C (PKC) as well as the phosphopeptides prepared from caldesmon phosphorylated in intact canine aortas that were stimulated to contract with PDBu. PKC phosphorylated three sites located in the C terminus: GSS*LKIEE, AEFLNKS*VQK and NLWEKQS*VDK, while h-caldesmon from intact tissue was phosphorylated at two separate sites also in the C terminus: VTS*PTKV and S*PAPK. By comparison to known substrate consensus sequences for various protein kinases these data suggest that h-caldesmon is directly phosphorylated by a proline directed protein kinase and not by PKC. PMID- 1601130 TI - Interleukin-4 stimulates collagen gene expression in human fibroblast monolayer cultures. Potential role in fibrosis. AB - A role for the cytokines produced by tissue-infiltrated inflammatory cells (mainly T-lymphocytes and mast cells) in the pathophysiology of fibrosis has been suggested by several groups. Among the products of these cells, interleukin-4 (IL 4) might be one of the factors involved in the initiation of the fibrotic process. We studied the effects of recombinant human IL-4 on human fibroblast monolayer cultures. IL-4 (10 and 100 U/ml) induced a dose-dependent increase of collagen production. Non-collagen protein synthesis was not significantly altered. A concomitant increase of pro-alpha 1(I) collagen mRNAs was observed, showing that IL-4 acts at a pre-translational level. PMID- 1601131 TI - Truncation of recombinant vimentin by ompT. Identification of a short motif in the head domain necessary for assembly of type III intermediate filament proteins. AB - Recombinant vimentin expressed in E. coli JM 101 cells is cleaved after cell lysis between arginines 11 and 12. The truncated vimentin is assembly incompetent. Expression of the same cDNA construct in BL21 cells, which lack the protease ompT, provides intact and polymerization-competent vimentin. The ompT cleavage site is contained in a short sequence motif (YRRMF) shared by the head domains of type III and IV intermediate filament (IF) proteins. We propose that a related motif present in the N-terminal 32 residues of lambda CII accounts for the known IF formation of a fusion protein formed with a truncated GFAP. PMID- 1601132 TI - The haemoglobin-like protein (HMP) of Escherichia coli has ferrisiderophore reductase activity and its C-terminal domain shares homology with ferredoxin NADP+ reductases. AB - Three soluble ferrisiderophore reductases (FsrA, FsrB and FsrC) were detected in Escherichia coli. FsrB was purified and identified as the haemoglobin-like protein (HMP) by size and N-terminal sequence analyses. HMP was previously isolated as a dihydropteridine reductase and is now shown to have ferrisiderophore reductase activity. Database searches revealed that the C terminal region of HMP (FsrB) is homologous to members of a family of flavoprotein oxidoreductases which includes ferredoxin NADP+ reductase (FNR). The combination of FNR-like and haemoglobin-like regions in HMP (FsrB) represents a novel pairing of functionally and structurally distinct domains. Structure function properties of other FNR-like proteins, including LuxG and VanB, are also discussed. PMID- 1601133 TI - The polypeptide chain fold in tyrosine phenol-lyase, a pyridoxal-5'-phosphate dependent enzyme. AB - The tyrosine phenol lyase (EC 4.1.99.2) from Citrobacter intermedius has been crystallised in the apo form by vapour diffusion. The space group is P2(1)2(1)2. The unit cell has dimensions a = 76.0 A, b = 138.3 A, c = 93.5 A and it contains two subunits of the tetrameric molecule in the asymmetric unit. Diffraction data for the native enzyme and two heavy atom derivatives have been collected with synchrotron radiation and an image plate scanner. The structure has been solved at 2.7 A resolution by isomorphous replacement with subsequent modification of the phases by averaging the density around the non-crystallographic symmetry axis. The electron density maps clearly show the relative orientation of the subunits and most of the trace of the polypeptide chain. Each subunit consists of two domains. The topology of the large domain appears to be similar to that of the aminotransferases. PMID- 1601134 TI - Structural analysis of the putative regulatory region of the rat gene encoding poly(ADP-ribose) polymerase. AB - A lambda EMBL3 clone containing the first three exons along with part of the 4th exon of the rat poly(ADP-ribose) polymerase gene was isolated from a genomic DNA library. This clone also contains 6.6 kbp of upstream sequences. Nucleotide sequence analysis of the proximal 5' 670 nucleotides flanking the major RNA start site of the rat gene does not reveal significant global homology with the same region of the human gene, but a series of short sequences are identical. Among these sequences are found two putative Sp1 binding sites along with a decanucleotide sequence responsible for the attachment of the transcription factor AP-2. PMID- 1601135 TI - Evaluation of the expression of the cationic peptide gene in various types of leukocytes. AB - To understand the regulation of the production of antimicrobial cationic peptide (CP) in leukocytes, expression of the CP gene was evaluated in various types of leukocytes using guinea pig neutrophils, monocytes, macrophages, eosinophils, lymphocytes and bone marrow cells. Acid-urea PAGE and SDS-PAGE/immunoblot analyses showed that CP was present in neutrophils and bone marrow cells, but not in other leukocytes. Northern blot and transcription run-off analyses revealed that only bone marrow cells expressed CP mRNA and transcribed the CP gene. Interestingly, in situ hybridization analysis using bone marrow cells demonstrated that CP mRNA was expressed in the neutrophil precursor cells, such as promyelocytes and myelocytes, but was not detected in the mature neutrophils and other bone marrow cells. Moreover, immunocytochemical study indicated that CP was present in the neutrophil precursor cells and the mature neutrophils in the bone marrow. Thus, the CP gene appears to be expressed during a limited period of neutrophil maturation, and CP is likely synthesized by the neutrophil precursor cells in the bone marrow. PMID- 1601136 TI - Selective inhibition of membrane fusion events in echinoderm gametes and embryos by halenaquinol sulfate. AB - Halenaquinol sulfate, a hydroquinone sulfate obtained from the sponge Xestospongia sapra, prevented cell membrane fusion events of echinaderm gametes but did not affect early embryonic development of fertilized eggs up to the gastrula stage. However, halenaquinol sulfate inhibited secretion of hatching enzyme, resulting in the formation of gastrulae that were surrounded by the fertilization envelope. Therefore, the use of halenaquinol sulfate offers a unique opportunity to analyze the role of secretory events in complex populations of cells without affecting other cellular functions. PMID- 1601137 TI - Was the Dalkon Shield a safe and effective intrauterine device? The conflict between case-control and clinical trial study findings. AB - OBJECTIVE: To compare the findings of the case-control and cohort studies used to indict the Dalkon Shield (A.H. Robins Company, Inc., Richmond, VA) with the findings of the Dalkon Shield clinical trials. DATA IDENTIFICATION: All published reports on the Dalkon Shield were identified through MEDLARS system (United States National Library of Medicine) searches and by cross checking all references in these reports. The same approach was used to identify all case control and cohort studies of the purported relationship between intrauterine devices (IUDs) and pelvic inflammatory disease (PID). STUDY SELECTION: Only studies of interval patients that included 50 or more women and 6 or more months of follow up that computed standard IUD event rates (rates of pregnancy and expulsion and removal for pain and bleeding) were selected for this study. All case-control and cohort studies identified were included except two case-control studies that included women with sterile chronic salpingitis. RESULTS: The 16 case-control and 2 cohort studies found or suggested that the Dalkon Shield increased the risk of PID. The 71 clinical trials of the Dalkon Shield show that when this device is inserted by an experienced clinician it is a safe and effective contraceptive method, comparable with other IUDs used at the time. There was no evidence of an increased risk of PID found in these clinical trials. CONCLUSIONS: This study offers convincing evidence that the indictment of the Dalkon Shield was a mistake. Additionally, this study shows that physician skill and experience is far more important to successful IUD insertion than previously recognized, a finding with considerable implications for IUD study designs and for marketing strategies. PMID- 1601138 TI - Earth, motherhood, and the intrauterine device. PMID- 1601139 TI - Reproductive performance after conventional metroplasty: an evaluation of 102 cases. AB - OBJECTIVE: To evaluate the influence of conventional metroplasty on reproductive performance of symmetric uterine anomalies and determine the complications of these procedures. DESIGN: A retrospective clinical analysis of consequently operated 102 women. SETTING: Institutional. PATIENTS AND PARTICIPANTS: One hundred two patients with bicornuate and septate uterus and a history of late recurrent abortion and/or preterm delivery were included in this study. INTERVENTIONS: Jones, Strassman, and Tompkins procedures for metroplasty and McDonald operation for cervical cerclage. MAIN OUTCOME MEASURE: The fetal survival rate has increased from 3.7% before operation to 75.0% afterwards. In only two patients uterine rupture was observed. RESULTS: Conventional metroplasty improves the fetal survival rate in women with symmetric uterine anomalies. CONCLUSIONS: Our results confirm the view that conventional metroplasty seems to be an operation of choice in women with symmetric uterine anomalies and a history of recurrent late abortion and preterm delivery. However, uterine rupture and postoperative infertility may be potential complications. PMID- 1601140 TI - The development of cytotoxicity in peritoneal macrophages from women with endometriosis. AB - OBJECTIVE: To assess the activation status of peritoneal macrophages from women with endometriosis. DESIGN: Peritoneal macrophages from patients undergoing laparoscopy were tested for cytotoxic activity against a cultured hepatoma cell line. SETTING: Patients were tested at initial laparoscopy or at the completion of therapy. PATIENTS AND PARTICIPANTS: Fertile controls (n = 27), infertile controls (n = 20), untreated endometriosis (n = 43), danazol-treated endometriosis (n = 22), and gonadotropin-releasing hormone agonist (GnRH-a) treated endometriosis (n = 13) were tested. INTERVENTIONS: Danazol (800 mg/d) or GnRH-a therapy for 6 months. RESULTS: Cytotoxicity was elevated in stage I and II endometriosis (P less than 0.02) and in infertile controls (P less than 0.05) compared with fertile controls. Cytotoxicity in stage III and IV endometriosis was lower (P less than 0.02) than in stage I and II endometriosis. Indomethacin in vitro increased cytotoxicity (P less than 0.05) in stage III and IV endometriosis but not in the other groups tested. Cytotoxicity in danazol or GnRH a-treated patients was increased (P less than 0.05 or greater) compared with untreated patients with comparable stage of disease. CONCLUSIONS: Peritoneal macrophage cytotoxicity in women with endometriosis is affected by (1) the extent of endometriosis, (2) prostaglandin metabolism, and (3) treatment with danazol or GnRH-a. PMID- 1601141 TI - Endometrial effect of transdermal estradiol and progestin ST-1435 in postmenopausal women. AB - OBJECTIVE: To study the endometrial effect of the transdermal synthetic progestin ST-1435. DESIGN: Prospective. SETTING: City Maternity Hospital, Helsinki, Finland. PATIENTS: Eleven postmenopausal women used transdermal estradiol (E2) patches for 6 weeks immediately before a vaginal operation for prolapse. For the last 10 days, 1 mg of ST-1435 transdermally in a gel was combined to the treatment. MAIN OUTCOME MEASURES: Blood samples were taken to follow serum concentrations of E2, follicle-stimulating hormone, and ST-1435. Endometrial samples for histologic examination were collected during the operation to evaluate the effect of the progestin. RESULTS: Transdermal absorption of ST-1435 resulted in reasonably constant serum concentrations of ST-1435 in each subject. A progestin effect on the endometrium was seen in 9 of 10 samples obtained. One sample did not show any progestin effect in spite of adequate ST-1435 levels, but this patient's E2 concentrations were low. CONCLUSIONS: When the estrogen stimulation was adequate, the transdermal ST-1435 induced a progestin effect on the endometrium, i.e., it had an end-organ effect. PMID- 1601143 TI - Prospective assessment of early fetal loss using an immunoenzymometric screening assay for detection of urinary human chorionic gonadotropin. AB - OBJECTIVE: To develop an economical, nonradiometric immunoenzymometric assay (IEMA) for the detection of urinary human chorionic gonadotropin (hCG) in studies of early fetal loss. To be effective, the IEMA must have a sensitivity equal to the standard immunoradiometric assay (IRMA) and sufficient specificity to eliminate the need for screening most nonconceptive cycles with the expensive and labor-intensive IRMA. DESIGN: Two different assays were used to measure hCG in daily early morning urine samples from potential conceptive cycles. SETTING: Women undergoing donor artificial insemination (AI) were evaluated in a prospective study. PATIENTS, PARTICIPANTS: Ninety-two women volunteers were selected on the basis of apparent normal reproductive health. INTERVENTIONS: Artificial insemination with nonfrozen donor semen was performed by cervical cup twice each menstrual cycle at 48-hour intervals, and daily urine samples were self-collected throughout the menstrual cycle. MAIN OUTCOME MEASURES: An IEMA was developed to detect urinary hCG using the same antibodies as in the standard IRMA; a study was designed to determine whether this nonradiometric assay could successfully detect the early fetal loss that was detected by the IRMA. RESULTS: Of 224 menstrual cycles analyzed by both assays, a total of six early fetal losses were detected by the IRMA. When the tentative screening rule was set to allow all six of these losses and 95% of future losses to be detected by the IEMA, an additional 34 false-positive results were detected by the IEMA. The specificity of the IEMA with this rule was calculated to be 84%. CONCLUSION: An IEMA based on the same antibodies used for the standard IRMA can serve as an efficient screening assay for the detection of early fetal loss. When the IEMA is used in this manner, nearly 80% of screened menstrual cycles can be eliminated without further testing by the IRMA. PMID- 1601142 TI - Nonpregnant women with a history of habitual abortion have normal and luteal function independent production of prostacyclin and thromboxane A2. AB - OBJECTIVE: To see if changes in prostacyclin and thromboxane A2 (TXA2) production during early pregnancy in women with habitual abortion is a pregnancy-induced change, we compared the production of these prostanoids in habitual aborters and in healthy controls in nonpregnant state and related it to luteal function. DESIGN: Comparison between patients (n = 16) with a history of at least three consecutive miscarriages and healthy controls without a history of abortions (n = 11). SETTING: Departments I and II of Obstetrics and Gynecology, University Central Hospital of Helsinki, Helsinki, Finland. RESULTS: Habitual aborters and control women exhibited no change in the urinary output of the stable degradation products of prostacyclin and TXA2 when studied between 0 and 2 and 5 and 8 days after the luteinizing hormone peak. Habitual aborters as a whole, or when subgrouped to those with normal (10 cycles) or defective luteal function (12 cycles) did not differ from the control series with regard to prostacyclin and TXA2 production. CONCLUSIONS: Productions of prostacyclin and TXA2 are not relative to the luteal function and are normal in nonpregnant women with a history of habitual abortion. PMID- 1601144 TI - Detection of interleukin-6 in human follicular fluid. AB - OBJECTIVE: To determine if interleukin-6 (IL-6) is a normal constituent of human follicular fluid (FF) after ovarian hyperstimulation and to assess whether IL-6 levels differ in conditions associated with immunological causes of infertility. DESIGN: After ovarian hyperstimulation for an in vitro fertilization (IVF) treatment cycle, FF samples were obtained at the time of oocyte retrieval. SETTING: Referral center at a tertiary care hospital. PATIENTS: Thirty women referred for IVF, including 10 patients with significant titers (greater than 40%) of antisperm antibodies and 10 with pelvic endometriosis. Ten patients with tubal infertility without antisperm antibodies or endometriosis served as controls. MAIN OUTCOME MEASURES: Analysis of FF levels for IL-6 using both bioassay and immunoassay. RESULTS: Bioactive (range 0.32 to 32.2 U/mL) and immunoreactive (range 0.34 to 13.6 ng/mL) IL-6 levels were detected in FF of all subjects after ovarian hyperstimulation. Follicular fluid IL-6 levels were substantially higher (3 to 30-fold) than that reported in serum. There was no difference in the mean concentrations of IL-6 levels between patients with antisperm antibodies, endometriosis, or tubal infertility. CONCLUSIONS: Bioactive and immunoreactive IL-6 are present in human FF after ovarian hyperstimulation, supporting a potential autocrine or paracrine role within the follicular microenvironment. PMID- 1601146 TI - Is fertility-problem stress different? The dynamics of stress in fertile and infertile couples. AB - OBJECTIVE: To compare the dynamics of fertility-problem stress experienced by wives and husbands in infertile couples with the dynamics of stress from other sources experienced by members of couples presumed to be fertile. DESIGN: Relationships of stress to four marriage factors and four aspects of life quality (subjective well-being) are examined within a causal modeling framework using data from structured interviews. SETTING: Face-to-face interviews were conducted in study participants' homes. PARTICIPANTS: Wives and husbands from 157 couples with primary infertility and from 82 presumed-fertile couples were studied. MAIN OUTCOME MEASURES: Final outcome measures were four multi-item scales assessing life quality with regard to the marriage, own self-efficacy, own health and appearance, and life as a whole. Intervening outcome scales measured four marriage factors: marital conflict, sexual self-esteem, sexual dissatisfaction, and frequency of intercourse. RESULTS AND CONCLUSIONS: Higher levels of stress, regardless of whether that stress was from attempting to solve a fertility problem or another problem, were related to reduced marital functioning and decreased life quality. For husbands, the strengths of the linkages did not depend on the source of the stress. For wives, however, the causal model suggested that fertility-problem stress had stronger negative impacts on sense of sexual identity and self-efficacy than did stress from other problems (P less than 0.05). Stress from any source had more impact on the lives of wives than of husbands, more impact on satisfaction with self and general well-being than on satisfaction with the marriage or health, and affected life quality mostly indirectly through its impacts on the marriage factors. PMID- 1601145 TI - Enzyme immunoassay method for total alpha gonadotropin in human urine samples. AB - OBJECTIVE: To develop and validate an assay for urinary luteinizing hormone (LH) metabolite that can be used for frozen-thawed urine. DESIGN: The study is in two parts: (1) selected urine samples were evaluated to determine all components of urinary LH metabolism, and then (2) 26 complete menstrual cycles were evaluated using daily matched blood and urine samples. SETTING: Urinary and serum samples were collected for normal women undergoing artificial insemination because of the infertility of their partners. PATIENTS: Patients were selected to have normal ovarian function. INTERVENTION: None. MAIN OUTCOME: Serum LH and urinary LH metabolites were measured in daily samples from 25 ovulatory cycles. RESULTS: The midcycle serum LH peak was highly correlated to the measurement of urinary LH metabolites in frozen:thawed urine samples. CONCLUSION: A simple enzyme assay for LH/LH-alpha can be used to detect the midcycle LH surge on frozen-thawed urine samples. This method has practical application in a situation that involves self collected urine samples stored frozen and later analyzed to determine the day of ovulation. PMID- 1601147 TI - Gonadotropin-releasing hormone agonist versus human chorionic gonadotropin for triggering follicular maturation in in vitro fertilization. AB - OBJECTIVE: To compare the use of gonadotropin-releasing hormone agonist (GnRH-a) with human chorionic gonadotropin (hCG) for triggering the final stage of follicular maturation for in vitro fertilization (IVF). DESIGN: In vitro fertilization outcome was determined in a randomized, prospective study. SETTING: The University of Toronto IVF program at The Toronto Hospital, Toronto General Division. PATIENTS AND INTERVENTIONS: One hundred seventy-nine women in the IVF program were given a subcutaneous injection of leuprolide acetate (500 micrograms) or an intramuscular injection of hCG (5,000 IU) 34 to 36 hours before oocyte retrieval. Vaginal progesterone (P) suppositories (50 mg) were used two times a day for luteal phase support. A subgroup of 41 women had serum estradiol (E2) and P levels determined 2 and 7 days after embryo transfer (ET). MAIN OUTCOME MEASURES: Pregnancy rates and luteal phase E2 and P were compared. RESULTS: In the GnRH-a group, there were 18 pregnancies from 84 ETs (20%). In the hCG group, there were 19 pregnancies from 95 ETs (19%). Luteal phase E2 and P levels were significantly lower in the GnRH-a group compared with the hCG group, and 18% of the former group had an apparent short luteal phase. CONCLUSIONS: Gonadotropin-releasing hormone agonist appears to be an effective alternative to hCG for inducing follicular maturation in IVF. The lower luteal phase E2 concentrations may potentially be beneficial in preventing ovarian hyperstimulation and for enhancing implantation. Better luteal phase support or a different dose of GnRH-a is needed to prevent luteal phase deficiency. PMID- 1601148 TI - A prospective randomized study of the optimum timing of human chorionic gonadotropin administration after pituitary desensitization in in vitro fertilization. AB - OBJECTIVE: To determine if there is an optimum time for the administration of human chorionic gonadotropin (hCG) after pituitary desensitization with gonadotropin-releasing hormone agonists (GnRH-a) has been achieved before ovarian stimulation for in vitro fertilization (IVF). DESIGN: Prospective randomized study. PATIENTS: Two hundred forty-seven patients undergoing an IVF treatment cycle who were randomly divided into three groups. INTERVENTIONS: All patients were administered subcutaneously buserelin acetate 500 micrograms/d from day 1 of the menstrual cycle. After pituitary desensitization had been achieved at least 14 days later, ovarian stimulation with human menopausal gonadotropin was commenced. Ovarian stimulation, cycle monitoring, oocyte recovery, and IVF and embryo transfer (ET) techniques were identical in all three groups. Patients in group 1 (n = 79) had hCG administered when the mean diameter of the largest follicle had reached 18 mm, at least two other follicles were greater than 14 mm, and serum estradiol (E2) levels were consistent with the number of follicles observed on ultrasound. Patients in groups 2 (n = 84) and 3 (n = 84) had hCG administered 1 day and 2 days, respectively, after the above criteria had been reached. RESULTS: The mean day of hCG administration (P less than 0.01), maximum serum E2 concentration (P = 0.06), number of days of serum E2 rise (P = 0.03), and mean diameter of the largest follicle (P less than 0.0001) were significantly different. There were, however, no significant differences in the mean number of preovulatory and medium size follicles, number of oocytes recovered or embryos transferred. There were also no significant differences in the oocyte recovery, fertilization and cleavage rates, in the number of embryos frozen, or in the pregnancy rates per initiated cycle and per ET. CONCLUSIONS: There is no significant advantage in the precise timing of hCG administration after pituitary desensitization with GnRH-a. PMID- 1601149 TI - The outcome of in vitro fertilization and embryo transfer in women with polycystic ovary syndrome failing to conceive after ovulation induction with exogenous gonadotropins. AB - OBJECTIVE: To assess the outcome of in vitro fertilization and embryo transfer (IVF-ET) in women with refractory polycystic ovarian syndrome (PCOS). DESIGN: Retrospective case series with an age-matched control group. SETTING: Ovulation induction and IVF programs in a tertiary referral center. PATIENTS AND INTERVENTIONS: Nine patients with PCOS who failed standard ovulation induction treatment (clomiphene citrate plus greater than or equal to 6 ovulatory human menopausal gonadotropin [hMG] cycles) underwent 19 cycles of IVF-ET. Forty age matched tubal factor patients who completed 40 cycles of IVF-ET served as a control group. OUTCOME MEASURES: Demographic features and IVF-ET cycle characteristics were compared using Student's t-test and Fisher's exact test. RESULTS: Cycles of IVF-ET in patients with PCOS were associated with higher estradiol levels (5,222 versus 4,009 pmol/L), lower hMG requirements (15.8 versus 19.6 vials), greater numbers of oocytes (7.6 versus 5.6), and lower fertilization rates (56% versus 75%) compared with tubal factor cycles (P less than 0.05). However, the number of embryos transferred (3.9 versus 4.0) and the clinical pregnancy rate per embryo transfer (24% versus 25%) did not differ significantly between the two groups. CONCLUSION: These results suggest that conception failure after six or more ovulatory hMG cycles in patients with PCOS does not adversely affect subsequent IVF performance. PMID- 1601150 TI - The effect of baseline complex ovarian cysts on in vitro fertilization outcome. AB - STUDY OBJECTIVE: To determine the effect of baseline complex ovarian cysts on controlled ovarian hyperstimulation and in vitro fertilization (IVF) outcome. DESIGN: Retrospective analysis with stratification by stimulation regimen and the presence or absence of surgically documented endometriosis. PATIENTS: Two hundred sixty-one women undergoing IVF from May 1, 1989 to December 31, 1990. MAIN OUTCOME MEASURES: The outcome measures assessed were the maximum estradiol (E2) concentration on day of human chorionic gonadotropin (hCG) administration, number of follicles with maximum diameter greater than or equal to 15 mm, number of follicles with maximum diameter greater than or equal to 12 mm, number of days to hCG administration, number of ampules of human menopausal gonadotropin (hMG) used, number of oocytes retrieved and fertilized, number of embryos transferred, and pregnancy and cycle cancellation rates. RESULTS: There were no statistical differences between cyst and noncyst groups in any of the above parameters of IVF performance. In a single subgroup, patients with endometriosis stimulated with hMG and patients with cysts had significantly lower E2 concentrations than patients without cysts. CONCLUSION: The presence of a complex cyst on a baseline ultrasound does not appear to adversely affect IVF cycle outcomes. PMID- 1601151 TI - Subzonal sperm microinjection in cases of severe male factor infertility and repeated in vitro fertilization failure. AB - OBJECTIVE: To examine (1) fertilization rates obtained with subzonal sperm microinjection when different numbers of sperm are injected into the perivitelline space; (2) when subzonal sperm microinjection is combined with dilute insemination; and (3) the association of semen quality characteristics with fertilization. DESIGN: Subzonal sperm microinjection and subzonal sperm microinjection combined with dilute insemination was performed in 109 and 41 cycles on patients in two clinical trials in Melbourne, Australia, and Bologna, Italy, respectively. PATIENT PARTICIPANTS: Couples who have experienced repeated in vitro fertilization failure or in whom the husband has severe male factor infertility. PRIMARY OUTCOME MEASURES: The number of oocytes fertilized after injection of different numbers of sperm into the perivitelline space, the number of patients transferred, and pregnancy outcome. RESULTS: The injection of multiple numbers of sperm into the perivitelline space failed to improve monospermic fertilization rates but caused an increase in polyspermic fertilization. In patients with initial semen parameters exhibiting greater than 50% motility or greater than 50% normal morphology fertilization rates were improved when subzonal sperm microinjection-treated eggs were incubated in a dilute insemination medium. Six pregnancies were obtained, two of which have progressed to term. CONCLUSIONS: When applied to male factor patients, the subzonal sperm microinjection technique results in a 14% to 15% fertilization rate. However, of the 102 embryos transferred only three (2.9%) fetal heart beats were obtained. PMID- 1601152 TI - The influence of varicocele on parameters of fertility in a large group of men presenting to infertility clinics. World Health Organization. AB - OBJECTIVE: To assess the role of varicocele in male infertility. DESIGN: Data analysis of a large population of couples who were systematically investigated for infertility. SETTINGS: Couples were recruited in 34 World Health Organization collaborating centers in 24 countries. PATIENTS: Nine thousand thirty-four men presenting as partner of infertile couples. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Physical findings, semen characteristics, coincidental pathology, and spontaneous pregnancies. RESULTS: Varicocele was found in 25.4% of men with abnormal semen, compared with 11.7% of men with normal semen. It was accompanied by decreased testicular volume, impaired sperm quality, and decline of Leydig cell secretion. Spontaneous pregnancies were as frequent in couples in whom the men did or did not have varicocele. CONCLUSION: Varicocele is clearly associated with impairment of testicular function and infertility. PMID- 1601153 TI - Semen analysis in human immunodeficiency virus infection. AB - OBJECTIVE: To examine the effect of human immunodeficiency virus (HIV) infection on semen quality and to investigate the role of clinical stage of infection, mode of virus acquisition, and azidothymidine (AZT) treatment. DESIGN, PATIENTS, MAIN OUTCOME MEASURES: Ejaculates from 39 HIV-seropositive men and 51 seronegative controls were compared using conventional semen analysis parameters. Centers for Disease Control (Atlanta, GA) classification and peripheral blood CD4 lymphocyte count of seropositive men were recorded at the time of semen analysis. Five patients provided semen before and after AZT treatment. RESULTS: Semen from seropositive men contained significantly fewer motile sperm (48.8% versus 58.8%, P = 0.001), more round cells (62% versus 28% subjects with density greater than 1 x 10(6)/mL, P = 0.003), and was more viscous (1.3 versus 0.5 cm, P less than 0.05) than semen from seronegative controls. The proportion of motile sperm was correlated with absolute number (r = 0.49, P = 0.004) and percentage (r = 0.37, P = 0.03) of CD4-positive lymphocytes in peripheral blood. Total sperm output, however, was preserved and was not correlated with lymphocyte count or symptomatic disease. Administration of AZT had no deleterious effect on sperm output or other semen variables. CONCLUSION: Human immunodeficiency virus infection per se does not significantly reduce sperm production, regardless of clinical stage or mode of acquisition; however, HIV-seropositive men produce more viscous semen containing fewer motile sperm and more round cells. PMID- 1601154 TI - Comparison of mixed antiglobulin reaction and direct immunobead test for detection of sperm-bound antibodies in subfertile males. AB - OBJECTIVE: To compare two methods of detection of surface bound antibodies on spermatozoa from subfertile males. DESIGN: Prospective comparison of direct mixed antiglobulin reaction (MAR) for immunoglobulin (Ig)G with direct immunobead test (IgG and IgA) applied to spermatozoa from male partners of infertile couples. Circulating unbound antibody measured by tray agglutination test in serum and seminal plasma in a representative proportion. SETTING: Seminology laboratory. PATIENTS: One hundred nine male partners of infertile couples. RESULTS: Highly significant correlation between direct MAR (IgG) and direct immunobed test (IgG) and between both of these tests and serum unbound antibody measured by tray agglutination test. Highly significant correlation between direct immunobead test (IgA) and seminal plasma unbound antibody measured by tray agglutination test, but no correlation with MAR (IgG). CONCLUSIONS: Mixed antiglobulin reaction (IgG) is a cheap, quick, and sensitive screening test, but immunobead test (IgA) provides useful additional information on class of antibody on spermatozoa that may be clinically more important. PMID- 1601155 TI - Effects of antibodies to sperm surface fertilization antigen-1 on human sperm zona pellucida interaction. AB - OBJECTIVE: To investigate the effects of antibodies to well-defined sperm surface antigens (the fertilization antigen [FA-1] and germ-cell antigen [GA-1]) and nuclear antigen (protamine) on human sperm-zona interaction. DESIGN: Number of total and acrosome-reacted human sperm bound to the human zona pellucida and the sperm movement characteristics assessed by computer-aided sperm analysis were evaluated after incubation of sperm with the antibodies. SETTING: Academic research environment approved by the Institute Review Board. PATIENTS: Human oocytes were obtained from ovaries removed at surgery. Semen from fertile donors was used in all assays. INTERVENTIONS: Human oocytes were stored in salt solution at -80 degrees C until used. Spermatozoa were treated with the antibodies to various sperm antigens. MAIN OUTCOME MEASURES: Total and acrosome-reacted sperm bound to zona pellucida and sperm movement characteristics were evaluated after 3 to 5 hours of incubation of the antibodies with human sperm. RESULTS: Anti-FA-1 antibodies significantly reduced human sperm fusion with zona-free hamster oocytes and sperm binding to the human zona pellucida but did not affect binding of acrosome-reacted sperm and sperm movement characteristics. Anti-GA-1 and antiprotamine antibodies did not affect sperm-oocyte interaction, acrosomal reaction, or sperm motility. CONCLUSIONS: Antibodies to FA-1 but not to GA-1 and protamine inhibit human sperm-zona interaction. PMID- 1601157 TI - Development of a technique for monitoring the contamination of human semen samples with leukocytes. AB - OBJECTIVE: To determine whether receptors for the N-formyl chemotactic peptide, FMLP, exist on the surface of human spermatozoa and regulate reactive oxygen species generation by these cells. DESIGN: Chemiluminescent analysis of reactive oxygen species generation by suspensions of human spermatozoa before and after removal of leukocytes using a magnetic cell separation technique. SETTING: Academic Research Institute. PATIENTS: Unselected male volunteers. RESULTS: Human sperm suspensions responded to FMLP and phorbol ester (PMA) with a burst of reactive oxygen species production. Autoradiographic analyses employing 3H FMLP and chemiluminescence studies involving the selective removal of leucocytes with anti-CD 45-coated magnetic beads demonstrated that the FMLP responses were because of leukocyte contamination. In contrast, reactive oxygen species production in response to PMA appeared to reflect the oxidant-generating capacity of both leukocytes and spermatozoa. CONCLUSION: The only cells present in the human ejaculate possessing detectable receptors for FMLP and capable of generating reactive oxygen species in response to this reagent come from the leukocyte population. Luminol-dependent, FMLP-induced, chemiluminescence provides a rational basis for monitoring the presence of leukocytes in suspensions of human spermatozoa. PMID- 1601156 TI - Sperm acrosin activity and fluorescence microscopic assessment of proacrosin/acrosin in ejaculates of infertile and fertile men. AB - OBJECTIVE: To compare biochemically active with immunoreactive sperm acrosin in fertile and infertile men. SETTING: This study was conducted in a tertiary care center, the Andrology Clinic, Department of Internal Medicine, University of L'Aquila. PATIENTS: We evaluated the males in 40 infertile couples with no recognized cause of female infertility and 20 fertile men. INTERVENTIONS: Ejaculates were collected under standardized conditions of abstinence. MAIN OUTCOME MEASURES: Total sperm acrosin activity was measured on a spectrophotometer in washed sperm stored at -80 degrees C for 1 to 6 days. The percent of spermatozoa immunostained by an antiserum against proacrosin/acrosin by indirect immunofluorescence (IFL) was determined on methanol fixed sperm smears. RESULTS: Biochemically active acrosin was correlated to immunoreactive acrosin (P = 0.0028), and both were inversely correlated to the percent of spermatozoa with an abnormal head (P = 0.00024 for acrosin activity and P = 0.0013 for IFL). Biochemically active and immunoreactive acrosin were lower in infertile compared with fertile men (P = 0.0012 and P = 0.0009, respectively). Sixty-eight percent of ejaculates with an acrosin activity lower than the limit value observed in fertile men showed a normal sperm morphology and a normal immunoreactivity for acrosin. CONCLUSIONS: A low sperm acrosin activity in teratospermic ejaculates is because of a lack or a defect of the immunogenic and functional domains of the protein. A low sperm acrosin in infertile men with normal semen parameters results from a possible functional defect of the enzyme that is immunohistochemically detected in spermatozoa. PMID- 1601158 TI - Preparation of human frozen-thawed seminal specimens using the SpermPrep filtration method: improvements over the conventional swim-up method. AB - OBJECTIVE: To examine the qualitative and quantitative characteristics of frozen thawed spermatozoa recovered through the SpermPrep (ZBL, Inc., Lexington, KY) filtration method or the swim-up technique for the purpose of intrauterine insemination (IUI) or other techniques for assisted reproduction. DESIGN, SETTING, PATIENTS: Thirty pairs of frozen specimens purchased from three commercial semen suppliers were used in this study. Each pair consisted of two aliquots from the same semen specimen. MAIN OUTCOME MEASURES: Spermatozoa recovered via the SpermPrep filtration and swim-up processes were evaluated for sperm numbers recovered, sperm motility, grade of sperm motility, percentage of morphologically normal spermatozoa, the response of spermatozoa to a hypo-osmotic environment (hypo-osmotic swelling test), and the amount of debris present. RESULTS: Application of the SpermPrep filtration method resulted in recovery of significantly greater numbers of spermatozoa (P less than 0.01) than were recovered with the swim-up method (31.1 +/- 3.2 x 10(6) versus 10.2 +/- 1.8 x 10(6) spermatozoa, respectively). This represents a mean recovery of approximately one half (49%) of all spermatozoa applied to the filter, whereas for the swim-up method, it was only 15%. The overall quality of recovered spermatozoa was virtually identical between the two methods (P greater than 0.05). The percent motile sperm improved by a mean of 18% to 20%, the grade of motility improved by a mean of 0.4 points (scale 0 to 4), the percent of morphologically normal spermatozoa increased by a mean of approximately 10%, the percent of spermatozoa reactive to a hypo-osmotic medium test increased by a mean of approximately 9%, and the debris score decreased by a mean of 0.2 to 0.3 points (scale 0 to 4). Most importantly, the mean total number of motile, morphologically normal spermatozoa after filtration through the SpermPrep column was 20.2 +/- 1.1 x 10(6), representing a mean recovery of 73% of the normal spermatozoa originally applied to the column. This was 316% greater than the yield obtained with the swim-up method (6.4 +/- 0.8 x 10(6)), which was significantly greater (P less than 0.01) than that recovered via the swim-up method. Also, the time required to harvest sperm through SpermPrep filtration was 20 to 25 minutes versus 80 minutes required for the swim-up method (P less than 0.05). CONCLUSION: Considering that the effectiveness of frozen-thawed semen is already limited when compared with fresh semen, SpermPrep filtration is the method of choice over the swim-up technique of sperm selection because the former provides significantly greater numbers of high quality sperm. It should be considered as an adjunct in semen preparation for IUI or other forms of assisted reproduction. PMID- 1601159 TI - Laser micromanipulation in the mouse embryo: a novel approach to zona drilling. AB - OBJECTIVE: To introduce the use of excimer lasers for penetration of the zona pellucida for micromanipulation purposes. DESIGN: Cryopreserved two-cell mouse embryos were thawed and exposed to the 248-nm line of a krypton fluoride excimer laser (Lambda Physik EMG 202, Goettingen, Germany) creating a 2 to 4-micron opening in the zona pellucida. SETTING: The Laser Ablation Laboratory at DuPont and the in Vitro Fertilization Laboratory at The Medical Center. INTERVENTIONS: The embryos were exposed in either phosphate-buffered solution (PBS) or modified human tubal fluid (HTF) with the laser power varying from 1 to 2 J/cm2 and cultured in Ham's F-10 medium (GIBCO, Grand Island, NY) with 0.4% bovine serum albumin. MAIN OUTCOME MEASURES: The outcome of each experiment was measured by blastocyst formation of laser-exposed embryos as compared with a set of unexposed control embryos handled in a similar fashion. RESULTS: Successful laser penetration of the zona pellucida was achieved using the 248-nm line of a krypton fluoride excimer laser. A higher blastocyst formation was found for embryos exposed in PBS. The higher optical absorption of the modified HTF partially inhibited embryo development. The blastocyst statistics increased 2.5-fold times by reducing the exposure of the embryos to ablation by-products. CONCLUSIONS: The use of a krypton fluoride excimer laser was introduced as a new method to open the zona pellucida of two-cell mouse embryos without interrupting blastocyst formation. PMID- 1601160 TI - Effects of left varicocele ligation in subfertile males with absent or atrophic right testes. AB - Fifteen subfertile males with absent or atrophic right testes underwent ligation of left varicoceles. Sperm concentration rose significantly with correction of scrotal thermographic abnormality and nine wives (60%) became pregnant. PMID- 1601161 TI - Mumps orchitis among soldiers: frequency, effect on sperm quality, and sperm antibodies. AB - This study reports on 72 young soldiers who suffered from a recent epidemic of acute mumps, with special emphasis on 19 who suffered from mumps orchitis and whose spermograms were in the fertility range. The immunological work-up for antibodies in sera or seminal plasma gave normal results for the patients diagnosed with orchitis, as well as the controls. The only remarkable finding was an increased risk of borderline significance for orchitis in smokers. The present study has proven that the presence of antisperm antibodies does not play a role in the etiology of mumps orchitis. PMID- 1601162 TI - Sperm microinjection twins: deoxyribonucleic acid fingerprinting. AB - The twins described are clearly nonidentical. The DNA fingerprints obtained show that they are the children of the putative mother and father, indicating the success of the microinjection procedure. PMID- 1601163 TI - Hot flushes during breast feeding? AB - The initiation of breast-feeding was accompanied by an increase in skin conductance followed by increased skin temperature. The pattern was similar to that observed during a menopausal hot flush and differed from sympathetic arousal and simple heating. PMID- 1601164 TI - Preoperative dilatation to facilitate repair of the high transverse vaginal septum. AB - A difficult resection and anastomosis of the high transverse vaginal septum at puberty may result in long-term vaginal stenosis. In this report, we describe an alternative approach to the patient with a transverse vaginal septum to include the following: (1) US-directed needle aspiration with broad spectrum antibiotic prophylaxis to decompress the hematocolpos and relieve the acute pain; (2) continuous suppression of ovulation to prevent acute recurrence of the hematocolpos; and, most importantly, (3) vaginal dilatation before resection of the obstructing membrane to lengthen the lower vagina and ensure postoperative compliance with dilatation before vaginal anastomosis is attempted. Using this approach, we have obtained excellent results in three patients. Further study is necessary to validate this surgical modification. PMID- 1601165 TI - High initial values of beta-subunits of human chorionic gonadotropin in ovum donation pregnancies indicate better implantation. AB - Fifty-five patients were treated by ovum donation, and a control group of 165 patients underwent IVF. The number of pregnancies obtained were 28 and 25, respectively. The initial beta-hCG values, as well as the PRs and implantation rates, in the ovum donation series were significantly higher than those of the IVF series. The clinical significance and potential application of these observations are discussed. PMID- 1601167 TI - Is there any correlation between follicular fluid hormone concentrations, fertilizability, and cytogenetic analysis of human oocytes recovered for in vitro fertilization? AB - Constituents of FF have been suspected to influence fertilizability and cytogenetic constitution of human oocytes. We therefore analyzed the FF concentrations of E2, P, T, and PRL for 114 oocytes recovered for IVF. Forty-six of these oocytes were fertilized and transferred to the maternal uterus. Among the unfertilized gametes, 27 were not analyzable, 30 were normal haploid, and 11 were classified as abnormal. There was no significant difference between fertilized and unfertilized oocytes for FF concentrations of E2, P, T, and PRL and for the E2:P ratios. Similarly, we detected no significant difference between normal and abnormal oocytes for these parameters. PMID- 1601166 TI - The effect of intraovarian injection of oxytocin and vasopressin on ovulatory function and numbers of ovarian follicles. AB - Our findings support the clinical use of vasoconstrictor solution within the ovary to achieve hemostasis. This will allow the gynecologist to avoid the thermocoagulative injury to the ovary by replacing electrosurgery and laser surgery with sharp incision accompanied by vasoconstrictor injection. PMID- 1601168 TI - Biochemical pregnancies or heterophil antibodies? PMID- 1601169 TI - [The 65th general meeting of the Japan Endocrine Society. Tokushima-shi, May 28 30, 1992. Abstracts]. PMID- 1601170 TI - The role of interleukin-6 in development. AB - Interleukin-6 is a member of a class of hormone-like molecules termed cytokines. The actions of IL-6 are highly pleiotropic. In adults IL-6 functions as a major mediator of inflammatory responses as well as inducing the synthesis of acute phase proteins by the liver following infection or injury. Based on in vitro and in vivo studies IL-6 also has important functions in regulating the development of multiple lineages of hemopoietic cells. It may also be an inflammatory mediator in the central nervous system. Although IL-6 has been found in early mouse embryos, its function has not yet been determined. Its expression by placental trophoblasts and maternal decidua suggests that it has some role in fetal-maternal interactions. Finally, the response of fetal hemopoietic progenitor cells to IL-6 suggests that IL-6 may have a broader action on the expansion and maturation of fetal precursors. New approaches such as those involving the disruption of the IL-6 gene in mice will be needed for a more complete understanding of IL-6's role in embryonic development. PMID- 1601171 TI - Differentiation inhibiting activity (DIA/LIF) and mouse development. AB - Analysis of the differentiation in culture of murine embryonic stem (ES) cells has resulted in the identification and characterization of the regulatory factor differentiation inhibiting activity (DIA). DIA specifically suppresses differentiation of the pluripotential ES cells without compromise of their developmental potential. DIA is identical to the pleiotropic cytokine leukaemia inhibitory factor (LIF) which has a broad range of biological activities in vitro and in vivo. It is produced in both diffusible and matrix-localised forms whose expression is differentially regulated. The compartmentalization of DIA/LIF and the modulation of its expression during stem cell differentiation and by other cytokines may be significant elements in the control of early embryo development. These features may also indicate general principles of the regulatory networks which govern stem cell renewal and differentiation in later development. PMID- 1601172 TI - The biology of granulocyte-macrophage colony-stimulating factor: effects on hematopoietic and nonhematopoietic cells. AB - Granulocyte-macrophage colony-stimulating factor (GM-CSF) is one of a family of glycoprotein cytokines that have potent effects in stimulating the proliferation, maturation, and function of hematopoietic cells. Deriving its name from its ability to stimulate the formation of macroscopic colonies containing neutrophils, eosinophils, macrophages, or mixtures of these cell types, GM-CSF stimulates the proliferation and maturation of myeloid progenitors, as well as functionally activating mature neutrophils, eosinophils, and macrophages. As most of the effects observed using GM-CSF in vitro have been shown to occur in vivo either in animal models or in human subjects, it is important to consider that GM CSF may also exert some biological effects on nonhematopoietic cells. In response to immunologic stimuli, immunologic surveillance cells and cells of the microenvironment are capable of producing GM-CSF. In vitro experiments indicate that GM-CSF production is tightly regulated. In that regard, GM-CSF is not present in measurable quantities in normal serum, but little is known about the in vivo process of GM-CSF production and regulation. The biologic capabilities of GM-CSF have triggered its widespread clinical use in situations where hematopoiesis is compromised. GM-CSF can act as a potent growth factor in vivo, increasing the number and enhancing the function of hematopoietic progenitors and mature cells. However, the precise in vivo effect that GM-CSF may have on normal and neoplastic cells of nonhematopoietic origin remains undefined. The full range of GM-CSF bioactivity is mediated following binding to its receptor. The presence of specific receptors for GM-CSF has been demonstrated in all responsive cells of hematopoietic lineage, as well as in nonhematopoietic cells, both responsive and unresponsive. In conclusion, a large body of work from a number of laboratories has defined the biology of GM-CSF. Currently available reagents and technology will provide additional insights into the biology of this molecule, thereby expanding our present definition and allowing us to explore the mechanisms regulating hematopoiesis. PMID- 1601173 TI - SCI/MIP-1 alpha: a potent stem cell inhibitor with potential roles in development. AB - The hemopoietic system represents a complex adult developmental system which allows the study of mechanisms of stem cell proliferative control and differentiation commitment. It is likely that information obtained from this model system will have implications for control processes regulating other hierarchical systems in the developing embryo as well as in the adult animal. We have recently identified and isolated a potent inhibitor of hemopoietic stem cell proliferation which we have labeled SCI/MIP-1 alpha. This inhibitor is also active on clonogenic epidermal cells and may thus be a more general stem cell inhibitor than was previously believed. The biology of this peptide is outlined in more detail below and the potential roles for such a factor in the developing embryo are also discussed. PMID- 1601174 TI - Territorial expression of three different trans-genes in early sea urchin embryos detected by a whole-mount fluorescence procedure. AB - We have developed a new procedure for detection of the protein product of chloramphenicol acetyltransferase (CAT) reporter genes in whole mounted sea urchin embryos. The position of a commercially available anti-CAT antibody is visualized by video or confocal microscopy, and thus the spatial domains of exogenous reporter gene expression can be determined with regard to the intact three-dimensional structures of the embryo. We show that in pluteus stage embryos CAT protein expression patterns for SM50 . CAT or CyIIIa . CAT reporter genes are similar to those previously obtained by in situ hybridizations with radioactive probes. Taking advantage of the superior resolution of cellular CAT expression patterns using the antibody visualization method, we found for the first time that, in addition to the expression in aboral ectoderm, some cells in the ciliated band of the pluteus express CyIIIa . CAT. The expression of a new fusion construct, CyIIa . CAT, was also examined. As expected from the localization of endogenous CyIIa mRNA, CAT protein was expressed under control of the CyIIa promoter in gut and skeletogenic mesenchyme cells. PMID- 1601175 TI - Cell-cell communication in the embryo of Caenorhabditis elegans. AB - We have investigated the pattern of cell-cell communication in embryos of the free-living soil nematode Caenorhabditis elegans. For this, we have established a method for microinjection of tracer dyes into individual blastomeres. After iontophoresis of fluorescent dyes of different molecular weights (Lucifer yellow, LY, M(r) 457; rhodamine-labeled dextran, RD, M(r) 4000), we can visualize intercellular communication pathways. The dye-spread of LY, indicating communication via gap junctions, becomes first visible in the late 2-cell stage. From the 4-cell stage onward all cells appear to be well coupled by communication channels, which allow the free diffusion of LY. In contrast, RD remains restricted to the injected cell and its descendants. After the primordial germcell P4 has been generated in the 24-cell stage, dye-spread of LY into this cell and its somatic sister D is delayed. However, the restricted dye-coupling of D is only temporary. After a brief period it joins the somatic compartment. With the beginning of the morphogenesis phase the two existing germline cells (the daughters of P4) are completely uncoupled from the soma, while the latter still forms a single dye-coupling compartment. Only during the second half of embryogenesis different separate somatic communication compartments are established. We followed the pattern of intercellular communication in the alimentary tract and found a progressive restriction into smaller dye-coupling units. Our data are compared to those found in other systems and discussed with respect to cellular determination and differentiation. PMID- 1601176 TI - The juvenile hormone analogue, methoprene, inhibits ecdysterone induction of small heat shock protein gene expression. AB - The small heat shock protein (hsp) genes of Drosophila are expressed in cultured cells in response to the moulting hormone, ecdysterone. We show here that juvenile hormone (JHIII) and the juvenile hormone analogue, methoprene, inhibit that induction in a dose-dependent manner. Heat shock induction is not inhibited. In transient expression studies using S3 line cells transfected with EcRE-CAT constructs, methoprene inhibition was found to require a 2-hr pretreatment (before ecdysterone addition), and methoprene's continued presence was essential. Farnesol, farnesyl acetate, and retinoic acid did not cause inhibition. Several models of methoprene inhibition are discussed. PMID- 1601177 TI - Fractal geometry of mosaic pattern demonstrates liver regeneration is a self similar process. AB - Partial hepatectomy causes compensatory, nonneoplastic growth and regeneration in mammalian liver. Compensatory liver growth can be used to examine aspects of patterns of cell division in regenerating tissue. Chimeric animals provide markers of cell lineage which are independent of growth and can be used to follow cell division patterns. Previous experimental evidence suggests that compensatory liver growth is uniform, without focal centers of proliferation. In this study we have extended that observation to include genes important in regeneration and cell cycle control in order to establish that nascent growth centers are not present in regenerating liver. There is a uniform spatial distribution of expression of these genes which is not related to mosaic pattern in the chimeras. While these genes may help regulate hepatocyte proliferation they do not appear to regulate patch pattern in the chimeras. With this information confirming uniform growth it was possible to use fractal analysis to test various hypothesized patterns of regenerative growth in the liver. The results of this analysis indicate that mosaic pattern does not change substantially during the regenerative process. Patch area and perimeter (the area occupied by or perimeter around cells of like lineage) increase during compensatory liver growth in chimeric rats without alteration of the geometric complexity of patch boundaries (boundaries around cells of like lineage). These tissue findings are consistent with previously reported computer models of growth in which repetitive application of simple decisions assuming uniform growth created complex mosaic patterns. They support the notion that an iterating (repeating), self-similar (a pattern in which parts are representative of, but not identical to the whole) cell division program is sufficient for the regeneration of liver tissue following partial hepatectomy. Iterating, self-similar cell division programs are important because they suggest a way in which complex patterns (or morphogenesis) can be efficiently created from a small amount of stored information. PMID- 1601178 TI - Regional injury and the terminal differentiation of satellite cells in stretched avian slow tonic muscle. AB - In the avian stretch model, the application of a weight overload to the humerus induces enlargement of the anterior latissimus dorsi (ALD) muscle and an increase in muscle fiber number which is accompanied by satellite cell activation. Myofiber injury may be an important stimulus to muscle fiber hyperplasia; therefore, light and electron microscopic evaluation was undertaken to determine if myofiber injury occurs in the stretch-enlarged ALD muscle of the adult quail. Autoradiographic studies were used to determine the terminal differentiation of labeled myogenic cells. A weight equal to 10% of body mass was attached to one wing of 27 adult quail and 3 birds were euthanized at 9 intervals of stretch, from 1 to 30 days. Birds were injected with tritiated thymidine at intervals ranging from 1 hr to 3 days prior to euthanization. Labeled nuclei were detected by light microscopic examination and identified by electron microscopy of a serial section. Three regions of the muscle were examined for disorganization of contractile elements, presence of cytoplasmic vacuoles, and/or phagocytic cell infiltration. The percentage of fibers exhibiting one or more of these criterion was significantly greater in the stretched ALD by Days 5 and 7 and declined at Day 10, reaching near control values by Day 14. Myofiber necrosis and phagocytic cell infiltration were only observed in the middle and distal regions of the stretched ALD muscle. Traditional signs of regeneration and repair were observed, including clusters of labeled myoblast-like cells and myotube formation within an existing basal lamina. New myotube formation with labeled central nuclei was also noted in the interstitial space, outside of basal lamina of persisting fibers. Labeled myonuclei were observed in the stretched fibers. These results demonstrate that chronic stretch produces regional injury and fiber degeneration and resultant regeneration in the ALD muscle of the adult quail. This may be an important stimulus for new fiber formation in this model. PMID- 1601179 TI - Fibulin is localized at sites of epithelial-mesenchymal transitions in the early avian embryo. AB - Fibulin is a 100-kDa calcium-binding, extracellular matrix (ECM), and plasma glycoprotein (Argraves et al., Cell 58, pp. 623-629, 1989; Argraves et al., J. Cell Biol. 111, 3155-3164). Immunoprecipitation analysis showed that antibodies against human fibulin react with an avian isoform (M(r) 100,000). The spatial and temporal distribution of fibulin was examined in the early avian embryo using immunofluorescence microscopy. In stage 15-22 quail embryos fibulin is a constituent of most basement membranes. Areas undergoing epithelial-mesenchymal transitions such as the endocardial cushions, developing myotomes, and neural crest display especially prominent immunostaining. In the early heart fibulin expression was most pronounced in the cardiac jelly at sites where endocardial cushion cells begin the migrations that lead to the formation of valvular and septal primordia. Laser scanning confocal microscopy showed extensive extracellular accumulations of fibulin on the surface of endocardial mesenchyme cells that were motile at the time of fixation (stage 19). These data suggest that enhanced deposition of fibulin at sites of epithelial-mesenchymal transitions may influence cell behavior. PMID- 1601180 TI - A nuclear extract, prepared from mass-isolated germinal vesicles, retains a factor able to sustain a cytoplasmic cycle of starfish oocytes. AB - The germinal vesicle (GV) of starfish oocytes contains a factor which is required to drive the cytoplasmic cycle of the meiotic division. Biochemical investigation of this factor has been difficult due to the small quantities of obtainable GV materials. To overcome this, we have developed a mass-isolation procedure for the GVs of starfish oocytes, which depends on the softening of the cortex of the oocytes by cytochalasins to enable the GVs to pass through the cortex by centrifugation. From the isolated GVs, we have prepared a soluble fraction which retains the activity to induce the cytoplasmic cycle in the meiotic division of oocytes. The factor was sensitive to both heat and papain, suggesting that it is a protein. PMID- 1601181 TI - Sequence, biochemical characterization, and developmental expression of a new member of the TGF-beta superfamily in Drosophila melanogaster. AB - More than 20 members of the transforming growth factor-beta (TGF-beta) superfamily of growth and differentiation factors have been implicated in development. One member of the TGF-beta family has been previously reported from Drosophila, the decapentaplegic (dpp) gene which is involved in embryonic dorsal/ventral polarity, embryonic gut formation, and imaginal disk development. Using PCR methods, we have identified a second Drosophila gene in the TGF-beta family. It encodes a protein product that is more similar to the TGF-beta-related human bone morphogenetic proteins (BMPs) 5, 6, and 7 than it is to the Drosophila dpp gene product. Because of its localization on the polytene chromosome map, we refer to this gene as 60A. Expression of a 60A cDNA in Drosophila S2 cells was used to determine that 60A encodes a preproprotein that is processed to yield secreted amino- and carboxy-terminal polypeptides. The carboxy-terminal peptides are recovered as disulfide-linked homodimers. The 60A transcripts and protein are first detected at the onset of gastrulation, primarily in the mesoderm of the extending germ band. As the germ band retracts, and throughout later stages of embryonic development, the 60A transcript and protein are most readily detected in cells of the developing foregut and hindgut. PMID- 1601182 TI - Xenopus blastulae show regional differences in competence for mesoderm induction: correlation with endogenous basic fibroblast growth factor levels. AB - Single cells from the animal cap and marginal zone (MZ) of mid-blastula stage embryos can undergo mesodermal or ectodermal differentiation as small clones under defined conditions in culture. Here we report that cells treated with Xenopus basic fibroblast growth factor (XbFGF), a mesoderm-inducing factor, usually differentiated into muscle. MZ cells, which normally give rise to most of the mesoderm, responded to lower concentrations of XbFGF than animal pole (AP) presumptive ectoderm cells. This difference in sensitivity correlated with immunocytochemical staining patterns that showed much greater levels of endogenous bFGF within MZ than AP cells in early embryos. At the mid-late blastula stage, nuclei of MZ cells were strongly immunoreactive. Nuclear staining persisted during gastrula and neurula stages, and extracellular bFGF also became apparent. Subsequently in somites, immunoreactivity of nuclei declined while that of the extracellular matrix was retained during tailbud stages. Nuclear localization of bFGF appeared to be temporally correlated with new transcription of muscle-specific genes, and extracellular bFGF was present during morphological differentiation. The results suggest that a cell's competence for mesoderm induction is related to its position in the embryo. PMID- 1601183 TI - Microtubule organization during maturation of Xenopus oocytes: assembly and rotation of the meiotic spindles. AB - Assembly of the meiotic spindles during progesterone-induced maturation of Xenopus oocytes was examined by confocal fluorescence microscopy using anti tubulin antibodies and by time-lapse confocal microscopy of living oocytes microinjected with fluorescent tubulin. Assembly of a transient microtubule array from a disk-shaped MTOC was observed soon after germinal vesicle breakdown. This MTOC-TMA complex rapidly migrated toward the animal pole, in association with the condensing meiotic chromosomes. Four common stages were observed during the assembly of both M1 and M2 spindles: (1) formation of a compact aggregate of microtubules and chromosomes; (2) reorganization of this aggregate resulting in formation of a short bipolar spindle; (3) an anaphase-B-like elongation of the prometaphase spindle, transversely oriented with respect to the oocyte A-V axis; and (4) rotation of the spindle into alignment with the oocyte axis. The rate of spindle elongation observed in M1 (0.7 microns min-1) was slower than that observed in M2 (1.8 microns min-1). Examination of spindles by immunofluorescence with antitubulin revealed numerous interdigitating microtubules, suggesting that prometaphase elongation of meiotic spindles in Xenopus oocytes results from active sliding of antiparallel microtubules. A substantial number of maturing oocytes formed monopolar microtubule asters during M1, nucleated by hollow spherical MTOCs. These monasters were subsequently observed to develop into bipolar M1 spindles and proceed through meiosis. The results presented define a complex pathway for assembly and rotation of the meiotic spindles during maturation of Xenopus oocytes. PMID- 1601184 TI - Expression pattern of skeletal muscle troponin T isoforms is fixed in cell lineage. AB - The expression of fast-muscle-type troponin T isoforms in chicken skeletal muscles was studied by two-dimensional SDS-polyacrylamide gel electrophoresis and immunoblotting. According to the pattern of troponin T isoform expression, chicken fast muscle was classified into two groups: One group expressed breast fast-muscle-type troponin T in addition to leg-fast-muscle-type troponin T, the other expressed only leg-fast-muscle-type troponin T. To the former group belong breast and wing fast muscles and some of the back fast muscles, and to the latter group belong the fast muscles in leg, abdomen, and neck. Transplantation of breast muscle into leg was performed in order to change the physical environment and to investigate the mechanism of isoform expression. Histological observation of the transplant revealed severe degeneration of muscle cells, followed by differentiation of myoblasts in which breast-muscle-type troponin T was eventually expressed. The results showed that the pattern of troponin T isoform expression is primarily fixed in the cell lineage, although nerves modulate it. PMID- 1601185 TI - Localization and synthesis of hyaluronic acid in the cumulus cells and mural granulosa cells of the preovulatory follicle. AB - Mural and cumulus granulosa cells synthesize hyaluronic acid (HA) and expand in vitro in response to follicle-stimulating hormone and a soluble factor(s) produced by fully grown oocytes. In the present study we examined HA synthesis and extracellular matrix organization by the two cell populations in vivo during the preovulatory period. After injection of human chorionic gonadotropin into pregnant mares' serum gonadotropin-primed animals, a progressive increase in HA synthesis was observed by the cumulus cell-oocyte complex (COC), and by the mural granulosa cells adjacent to the antrum (antral granulosa cells). The outermost layers of mural granulosa cells (peripheral granulosa cells) did not synthesize HA. Net HA synthesis was approximately 4 pg/cell for COCs isolated after full expansion induced either in vivo or in vitro, whereas the total HA content and cell number in the ovulated COC (approximately 11 ng HA and approximately 3000 cells per COC) were about threefold higher than for COCs expanded in vitro (approximately 4 ng HA and approximately 1000 cells per COC). The increased cell content of ovulated COCs appears to be primarily the result of inclusion of proximal mural granulosa cells which synthesize HA in response to the oocyte factor(s) and become incorporated in the expanded COC extracellular matrix mass. Media conditioned by oocytes enclosed in the cumulus cell mass (intact COCs) contained only 10-20% of the HA-stimulatory activity of media conditioned by an equal number of isolated oocytes when tested on mural granulosa cell cultures. Further, HA-stimulatory activity of media conditioned by isolated oocytes was dramatically reduced (approximately 70%) by preincubation for 5 hr with cumulus cells compared to preincubation in the absence of cells. The results suggest that differences in HA synthesis between subregions of membrana granulosa depend on a diffusion gradient of the oocyte factor(s). PMID- 1601187 TI - Cell lineages, developmental timing, and spatial pattern formation in embryos of free-living soil nematodes. AB - From soils of various origins we have isolated a number of nematode strains and cultured them on agar plates. We have analyzed their anatomy, reproduction, and particularly their pattern of embryogenesis. With respect to early cleavage we can define six different classes. The basic scheme of embryogenesis is similar in all strains but considerable differences were observed in detail. Embryogenesis is more than five times longer in the slowest strain than in the fastest. The following general correlation was found: The slower embryogenesis proceeds in a strain, the relatively earlier the cleavage of germline cells occurs. In the fastest strain the primordial germ cell P4 is present at the 24-cell stage, while in the slowest strain it is already generated in the 5-cell stage. We hypothesize that germline cleavages have to occur within a certain time limit to preserve germline quality. The typical reversal of cleavage polarity in the division of the germline cell P2 is absent in the slowest, on other grounds apparently more primitive strain. This results in an unusual spatial arrangement of cells transiently. However, prior to gastrulation as a consequence of compensatory cell migrations (which may indicate the necessity for cell interactions), the pattern becomes very similar to that in the other strains. We propose that a standard cellular configuration is required at the beginning of gastrulation to ensure normal further development. Early cell interactions might be necessary to achieve this standard pattern. In about half of the analyzed strains cellular structures can be marked with an antibody raised against germline-specific granules of Caenorhabditis elegans. Our results do not support the notion that the staining pattern for P granules is a useful indicator for phylogenetic relationship. PMID- 1601186 TI - Expression and localization of villin, fimbrin, and myosin I in differentiating mouse F9 teratocarcinoma cells. AB - F9 embryonic carcinoma cells are a multipotent cell line which can be induced to differentiate into cells resembling the visceral endoderm, an extraembryonic absorptive epithelium characterized by apical microvilli. We have examined the role of villin, fimbrin, and myosin I, the major actin-binding proteins in the intestinal and visceral yolk sac microvilli, in the development of epithelial polarity and the assembly of the microvillus cytoskeleton in differentiating F9 cells. By immunoblot analysis villin was first detected at 4 days of differentiation. Confocal microscopy localized villin at Day 4 to the apical surface and by Day 6 to the basolateral surfaces as well. In comparison, fimbrin and myosin I were both present in undifferentiated F9 cells and became associated with the apical surface after villin during differentiation to visceral endoderm. The accumulation of villin, fimbrin, and myosin I at the apical surface in differentiating F9 cells correlated with the appearance of microvilli containing organized actin filament bundles. Two mouse villin cDNAs were isolated and characterized to examine villin expression during F9 differentiation. Mouse villin was encoded by two transcripts (3.8 and 3.4 kb) which differ in their 3' noncoding region. Both villin mRNAs were first detected by Day 4 of differentiation and their appearance coincided with expression of the visceral endoderm marker alpha-fetoprotein. The pattern of expression and order of accumulation of villin, fimbrin, and myosin I in differentiating F9 cells are common to developing gut and yolk sac epithelium. This suggests that microvillus assembly is directed by a sequence of temporally and spatially regulated localizations of these actin-binding proteins. PMID- 1601188 TI - Modifiers of bx1 alter the distribution of Ubx proteins in haltere imaginal discs of Drosophila. AB - The bithorax (bx) mutations in the Ultrabithorax (Ubx) gene of Drosophila melanogaster cause homeotic transformations of anterior third thoracic structures (T3a) toward anterior second thoracic structures (T2a) in the adult fly. A corresponding loss of Ubx protein expression in T3a of bx imaginal discs has been observed (White and Wilcox, 1985). We describe two genetic loci which modify the bx-induced transformation. A locus which we map very close to the pink peach (pp) gene suppresses the bx1 phenotype. In contrast, mutations in the suppressor of sable (su(s)) gene enhance the bx1 phenotype. A correlation was observed between patterns of Ubx protein expression and the phenotypic transformations observed. PMID- 1601190 TI - FM systems as primary amplification for children with profound hearing loss. AB - The use of FM systems as primary amplification for children with severe and profound hearing loss is discussed. The FM advantage for improving speech perception and for reducing the detrimental effects of distance, noise, and reverberation is described. Both hypothetical and actual cases are used to demonstrate the FM advantage. An evaluation method for selecting an appropriate FM system is described. PMID- 1601189 TI - Characterization of the epidermal growth factor receptor in preimplantation pig conceptuses. AB - Embryos recovered from sows on Days 9-13 of pregnancy (Day 0 = first day of estrus) exhibited saturable and time-dependent specific binding of 125I-epidermal growth factor (EGF). The specific binding (pg/mg protein) was greater (P less than 0.001) for Day 13 elongated conceptuses than for conceptuses of earlier stages. Scatchard analyses showed two classes of binding sites (Kd = 7.0 +/- 2.6 x 10(-11) M, Bmax = 6.2 +/- 1.4 fmol/mg protein and Kd = 3.4 +/- 0.2 x 10(-8) M, Bmax = 420 +/- 80 fmol/mg protein). The EGF receptor in Day 13 conceptus membranes is a 170-kDa protein and was phosphorylated in the presence of EGF and adenosine triphosphate. EGF stimulated protein tyrosine kinase activity about 1.6 fold over basal levels. The results show that the preimplantation pig conceptus possesses EGF-binding sites with the properties of functional EGF-receptors. PMID- 1601191 TI - Correlates of successful hearing aid use in older adults. AB - OBJECTIVE: To evaluate whether age, education, functional handicap, degree of hearing loss, amount of hearing and speech recognition gain achieved with hearing aid, locus of control, visual acuity, manual dexterity, number of comorbid diseases, and number of medications predict which elderly individuals with hearing loss are likely to benefit from hearing aids. DESIGN: A logistic regression prediction model for hearing aid benefit was developed on a training set of 89 individuals and verified in a test set of 87 individuals. Hearing aid success was assessed 4 mo after hearing aid adminstration. It was defined by assessing hearing aid satisfaction, functional handicap change post-hearing aid, and number of hours of weekly hearing aid use. SETTING: All patients were elderly male veterans from the Audie L. Murphy Memorial Veterans Hospital. There were no differences in demographic or clinical characteristics in training versus test set individuals. RESULTS: Several variables, including baseline perceived functional handicap, education, number of medications, and age correlated with individual success measures. However, no variables consistently correlated with all success measures. The accuracy of prediction rules for success utilizing the variables ranged from 75 to 88% in the training set, and 54 to 84% in the test set. CONCLUSION: Although certain baseline factors were statistically significantly related to individual measures of successful hearing aid use, no factors were good enough to consistently differentiate successful from unsuccessful hearing aid candidates. PMID- 1601192 TI - Noise reduction hearing aids: release from masking and release from distortion. AB - Automatic frequency response (AFR) hearing aids usually reduce their low frequency gain in the presence of noise; several investigators have reported improved recognition of high-frequency speech information in low-frequency band limited noise with AFR versus non-AFR hearing aids. In this work, masking patterns (masked threshold for frequency-modulated probe tones as a function of probe frequency) were obtained for a narrowband low-frequency noise. Speech recognition threshold for a set of high-frequency loaded monosyllables also was obtained in the presence of the same noise. Aided speech and masking pattern data for one normal and two hearing-impaired subjects wearing a master hearing aid incorporating a commercially available AFR circuit showed modest AFR effects. Moreover, masking noise spectra measured in ear canals of subjects wearing the master hearing aid showed evidence of substantial hearing aid-generated distortion products in the AFR-off condition. Results obtained from the normal subject listening with a low-distortion laboratory simulation of an AFR hearing aid showed greater release from masking for the same low-frequency attenuation as provided by the hearing aid. Improvements of speech recognition in noise observed with AFR hearing aids may result from some combination of release from upward spread of masking and reduction of distortion products generated by the hearing aid in the non-AFR setting. PMID- 1601193 TI - Allergic contact dermatitis from the earmolds of hearing aids. AB - Hearing aid users with longstanding and severe dermatitis in the ear canal were examined by a dermatologist and patch tested. In 6 of 22 (27%) patients, contact allergy to the earmold material was found. Four of the six had a positive test reaction to methyl methacrylate and two also to triethyleneglycol dimethacrylate and urethane dimethacrylate. Positive patch test reactions to substances used for topical treatment were found as well. Routines including liberal patch testing for this group of patients are suggested. PMID- 1601194 TI - Identification of middle ear dysfunction in young children: a comparison of tympanometric screening procedures. AB - Two acoustic immittance screening procedures were evaluated in conjunction with pneumatic otoscopy, performed by a pediatric otolaryngologist. The subjects were 204 3- and 4-yr-old children from a rural area in eastern North Carolina. Pass fail criteria were examined using two middle ear screening procedures: (1) a "traditional" procedure based on measures of tympanometric peak pressure and acoustic reflexes, and (2) the tympanometric measures contained within the American Speech-Language-Hearing Association's (ASHA) revised Guidelines for Screening for Hearing Impairment and Middle Ear Disorders. The traditional procedure resulted in low specificity but high sensitivity, whereas ASHA's immittance procedure resulted in high specificity but only moderate sensitivity. The negative predictive value was very high for both procedures; however, positive predictive value was low, especially for the traditional procedure. Advantages and disadvantages of the two procedures and future research needs are discussed. PMID- 1601196 TI - Monaural versus binaural hearing: ease of listening, word recognition, and attentional effort. AB - Forty-eight normal-hearing subjects performed ease of listening, word recognition, and attentional effort tasks for speech in noise under binaural and two simulated unilateral conductive hearing loss (monaural) conditions. The two monaural conditions differed as a function of unoccluded ear orientation to the primary signal (monaural-near and monaural-far). Ease of listening ratings and word recognition scores were significantly poorer during monaural listening and significantly affected by ear orientation to the speech signal. Attentional effort was not significantly affected by changing from binaural to monaural-near listening, but was significantly poorer in the monaural-far condition than in either of the other listening conditions. There was a significant correlation between ease of listening ratings and word recognition, but no correlation between attentional effort and either ease of listening or word recognition. PMID- 1601195 TI - Processing the telephone speech signal for the hearing impaired. AB - Speech intelligibility scores from 16 subjects with sensorineural hearing loss were evaluated using a digitized version of the California Consonant Test that was presented via headphones through a 300 to 3000 Hz bandpass filter to simulate the telephone band. Each subject was tested with an unprocessed signal that was frequency-equalized to compensate for the individual's hearing loss, and a signal that was equalized and compressed by the use of a compressor compression technique. Subjects were tested at three sound pressure levels above a pure-tone average threshold for frequencies 1 and 2 kHz. Two digital signal processing techniques designed to compensate for high-frequency hearing loss were examined: frequency domain processing and time domain processing. Frequency domain involved modification of the short-term spectrum obtained through a fast Fourier transform, whereas time domain processing involved passing the signal through a bank of finite impulse response filters. Both techniques showed significant intelligibility improvements (15-30%). In a second experiment, 16 additional subjects with high-frequency hearing loss compared an amplified telephone signal to three processed signals: (1) 6 dB per octave emphasis; (2) a signal frequency equalized for their hearing loss; and (3) a signal that was equalized for their hearing loss and was compressed according to their uncomfortable loudness levels. Most subjects preferred the signal with the 6 dB per octave emphasis. PMID- 1601197 TI - Frequency specificity of the auditory brain stem response to bone-conducted tones in infants and adults. AB - Auditory brain stem responses were obtained from normal-hearing infants and adults in response to bone-conducted 500 and 2000 Hz tones presented in quiet and high-pass noise masking. The tones were presented at 70 (500 and 2000 Hz) and 46 (2000 Hz) dB peak to peak equivalent (re: 1 dyne RMS). The high-pass noise-masked waveforms were subtracted in succession to obtain derived responses, providing estimates of the cochlear regions contributing to the nonmasked responses. Findings indicate that the auditory brain stem response to bone-conducted 500 Hz tones is frequency specific for both infants and adults. For 2000 Hz tones, the results show maximum amplitudes for cochlear regions representing the nominal frequency of the tone for adults. For infants, maximum response amplitudes for the derived responses to 2000 Hz, 70 dB tones were obtained within 1/2 octave of the nominal frequency (1410-2000 Hz). Wave V latencies of the derived responses are similar for both groups for 2000 Hz tones, but shorter for infants to 500 Hz tones, supporting the hypothesis that low-frequency bone-conducted stimuli are effectively more intense in infants than adults. PMID- 1601198 TI - Using the derived auditory brain stem response to estimate traveling wave velocity. AB - An estimate of the traveling wave velocity (TWV) was evaluated in 18 young adults to determine the technique's applicability as a possible tool in evaluating Meniere's disease. This TWV estimation uses a derived auditory brain stem response procedure requiring high-intensity masking. The results indicate that on average, TWVs were similar to those obtained via psychophysical measures or electrocochleography. However, instances of undermasking, due to subjects' intolerance, resulted in a number of subjects exhibiting faster than expected TWVs. PMID- 1601199 TI - An update on exposure and effects of lead. AB - Lead is perhaps the oldest of industrial toxins, dating back to Roman times. Despite the historic knowledge of lead, this metal remains a public health concern today. This is due both to the pervasiveness of lead in the environment and to the awareness of toxic effects of lead occurring at exposure levels lower than previously thought harmful. At the 1991 Annual Meeting in Dallas, Texas, the Society of Toxicology hosted the symposium: "An Update on Exposure and Effects of Lead." The goal of the symposium was to present an overview on critical issues associated with lead toxicity--ranging from fundamental mechanisms, such as the role of lead binding proteins, to assessment of the potential effectiveness of lead abatement measures, such as the impact on blood lead of home deleading. These issues are summarized in Fig. 1 using the four-stage paradigm of risk assessment as described by the National Academy of Science (NRC, 1977). Clearly, understanding potential impacts of lead in humans is interdisciplinary, involving the efforts of toxicologists, pathologists, epidemiologists, environmental chemists, and others. The following is a summary of each of the individual presentations. PMID- 1601200 TI - Reduction by pyridostigmine pretreatment of the efficacy of atropine and 2-PAM treatment of sarin and VX poisoning in rodents. AB - This study concerned the effect of pyridostigmine pretreatment on (a) the antidotal efficacy of atropine and 2-PAM in sarin, tabun, and VX poisoning in mice and guinea pigs and on (b) the oxime-induced reactivation of VX-inhibited whole blood acetylcholinesterase (AChE) of guinea pigs. One hour prior to organophosphate (OP) challenge with sarin, tabun, or VX, animals were given oral doses of pyridostigmine to induce approximately 30 and 60% inhibition of whole blood AChE; controls received vehicle. Mice were challenged im and guinea pigs sc with the OP compounds. Treatment with atropine (11.2 mg/kg to mice; 32 mg/kg to guinea pigs) plus 2-PAM (25 mg/kg) was given im at 10 sec postchallenge in mice and 1 min postchallenge in guinea pigs. In the reactivation experiments, pyridostigmine or saline was given im to guinea pigs 30 min prior to VX (8.24 micrograms/kg, sc), atropine (16 mg/kg) was given im at 1 min, and 2-PAM (25 mg/kg) at 16 min postchallenge. Pyridostigmine significantly enhanced the efficacy of atropine and 2-PAM against tabun in both species. In contrast, pyridostigmine reduced or did not increase the efficacy of atropine and 2-PAM against sarin or VX in both species. Recovery of VX-inhibited AChE by 2-PAM was decreased significantly in pyridostigmine pretreated animals. The results suggest that pyridostigmine pretreatment may adversely effect the efficacy of atropine and 2-PAM as antidotes for VX and sarin intoxication. PMID- 1601201 TI - The distribution, elimination, and in vivo biotransformation of aldicarb in the rainbow trout (Oncorhynchus mykiss). AB - The distribution and elimination of [14C]aldicarb, administered orally and by intraperitoneal (ip) injection, was examined in the rainbow trout (Oncorhynchus mykiss). Tissue residues were determined by monitoring radioactivity at various time periods up to 96 hr in trout administered [14C]aldicarb orally. Periodic water samples and a single tissue residue radioactivity level were obtained after 24 hr in free swimming and spinally transected fish which received [14C]aldicarb via intraperitoneal injection. Aldicarb appears to be absorbed rapidly (99% within 3 hr) and distributed to all tissues. Elimination profiles from both dosage groups demonstrate a rapid alpha phase (oral 24 hr; ip 3 hr) probably due to branchial excretion (96% after ip injection) followed by a slower beta phase (oral 107 hr; ip 28 hr) suggesting a deeper compartment such as muscle. [14C]Aldicarb and/or its metabolites were slowly being transported to the bile after 24 hr. The in vivo biotransformation of [14C]aldicarb was examined in spinally transected trout 24 hr after ip injection. The major metabolite found was aldicarb sulfoxide (7.6%) along with lesser amounts of aldicarb oxime (5.4%). PMID- 1601202 TI - Urothelial hyperplasia induced by carbonic anhydrase inhibitors (CAIs) in animals and its relationship to urinary Na and pH. AB - Investigations of MK-0927 and acetazolamide, both carbonic anhydrase inhibitors (CAIs), showed that urothelial hyperplasia develops in rats and mice, but not in rabbits, dogs, or monkeys. Rats given MK-0927 orally had a rapid onset of the change which regresses often completely despite continued treatment. Increased urinary pH and Na excretion, pharmacologic effects of CAIs, tended to be correlated with lesions. Rats given MK-0927 orally and fed either a 5% potassium phosphate meal or a 5% ammonium chloride meal had reduced urinary pH and/or urinary Na excretion and a reduced incidence of urothelial hyperplasia. Rats given MK-0927 orally and fed a low Na diet had very low urinary Na and essentially no urothelial hyperplasia. It was concluded that a clear relation exists between increased urinary Na excretion and pH, and urothelial hyperplasia induced by CAIs. These results in rats confirm the importance of increased Na and pH as stimuli for the development of urothelial hyperplasia. PMID- 1601203 TI - Calibration of respiratory gas exchange measurements in inhalation toxicology studies. AB - The use of simplifying assumptions for determining respiratory gas exchange is associated with substantial errors in the estimates of oxygen consumption (VO2) and carbon dioxide production (VCO2). Studies were done to estimate the magnitude of these errors under common exposure conditions, and a simple procedure that reveals these errors is described for calibrating an open flow respirometer. The errors associated with various simplifying assumptions ranged from -1 to -21% for VO2, 0.1 to 15% for VCO2, and 4 to 45% for the respiratory exchange ratio (R). The calibration was performed with a standard calibration gas elevated in CO2 and depressed in O2 relative to air and bled into the respirometer at a measured flow rate. Dilution of the gas into the respirometer airstream simulates the effect of respiratory gas exchange, and expected values of VO2, VCO2, and R compared to measured values provide a check of accuracy of flow and gas fraction measurements, a test for system leaks, and a test for the effects of any simplifying assumptions on the calculation of respiratory gas exchange. PMID- 1601204 TI - Dose-related effects of the hepatocarcinogen, Wy-14,643, on peroxisomes and cell replication. AB - The dose and time dependency of peroxisome proliferation and hepatocyte replication was evaluated in the liver of rats fed the peroxisome proliferator and hepatocarcinogen, Wy-14,643. Male F344 rats were fed NIH07 diet blended with Wy-14,643 at 0, 5, 10, 50, 100, or 1000 ppm for 1, 3, 6, or 13 weeks. Hepatomegaly was induced by Wy-14,643 at all doses and at all time points. Peroxisome proliferation was present in rats fed 5 ppm Wy-14,643 as early as 1 week, as determined by the peroxisome-specific NAD+ reduction of palmitoyl CoA (PCO) and the peroxisome-associated activity of carnitine acetyltransferase (CAT) (5- and 11-fold over control, respectively). The elevations of PCO and CAT were dose-dependent from 5 to 50 ppm and then plateaued from 50 to 1000 ppm throughout the treatment period. Hepatocellular replication, evaluated by nuclear histoautoradiography ([3H]thymidine labeling, 6-day infusion), was increased in all Wy-14,643 dose groups after 1 week of treatment (5 ppm, 4-fold; 10 ppm, 5 fold; 50 ppm, 13-fold; 100 ppm, 12-fold; and 1000 ppm, 13-fold over controls). However, in 5 and 10 ppm groups this cell replication returned to control levels by 3 weeks. In contrast, 50, 100, and 1000 ppm groups had sustained increases in cell replication up to 13 weeks (13 weeks: 6-, 7-, and 9-fold over controls, respectively). We have demonstrated that Wy-14,643 can induce peroxisome proliferation at 5 ppm, a dose 200 times lower than the dose shown to be highly hepatocarcinogenic in rats (100% incidence by 60 weeks).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601205 TI - Health effects of atmospheric acid aerosols: a model problem in inhalation toxicology and air pollution risk assessment. AB - A symposium entitled, Health Effects of Atmospheric Acid Aerosols: A Model Problem in Inhalation Toxicology and Air Pollution Risk Assessment, was held at the 30th Annual Meeting of the Society of Toxicology (SOT) in Dallas, Texas. The symposium was sponsored by the Inhalation Toxicology Specialty Section of SOT, and was organized to integrate evidence from various disciplines concerning health effects from acid aerosols in ambient air. PMID- 1601206 TI - Chronic toxicity carcinogenicity studies of triethanolamine in B6C3F1 mice. AB - The chronic toxicity and carcinogenic potential of triethanolamine was examined in B6C3F1 mice. Triethanolamine, dissolved in distilled water at levels of 0 (control), 1, and 2%, was given to groups of 50 males and 50 females ad libitum in drinking water for 82 weeks. Neoplasms developed in all groups, including the control group, but no dose-related increase of the incidence of any tumor was observed in treated groups of both sexes. There were no adverse effects as regards survival of the mice, organ weights, and specific incidence of neoplasms in the treated, compared to the control group. This chronic toxicity test provides no evidence of carcinogenic potential of triethanolamine in B6C3F1 mice. PMID- 1601207 TI - Dermal absorption of dilute aqueous chloroform, trichloroethylene, and tetrachloroethylene in hairless guinea pigs. AB - Percutaneous absorption was measured in female hairless guinea pigs dermally exposed for 70 min to very dilute (approximately 10 to 100 ppb) aqueous solutions of 14C-labeled chloroform (CF), trichloroethylene (TCE), or tetrachloroethylene (PCE) in an airtight glass chamber containing no headspace. Similar experiments were conducted using aqueous solutions of TCE at 100,000 ppb. Dermal uptake was estimated by comparing the rate of radiolabel loss from chamber water in systems with and without experimental animals. After each low-concentration dermal-uptake experiment, radiolabel in total urine and feces excreted postexposure was measured and expressed as a fraction of corresponding estimated dermal uptake. For each of the compounds studied, the mean value of these fractions did not differ significantly from that obtained using animals injected with a known dose of that compound, indicating that our experimental system yielded accurate dermal uptake estimates. The mean permeability coefficients obtained range from 0.13 cm/hr (CF) to 0.37 cm/hr (PCE); those obtained using low- vs high-concentration TCE are not significantly different. The value for CF is very close to one we calculate here from recently published data on CF uptake in human volunteers dermally exposed to aqueous CF while showering with normal tap water. Our results suggest that dermal absorption may be an important route of human exposure to chlorinated volatile organic compounds in domestic water supplies. PMID- 1601208 TI - Immunotoxicological characteristics of sodium methyldithiocarbamate. AB - This study was conducted to assess immunotoxicological effects and selected general toxicological effects of sodium methyldithiocarbamate (SMD). Initially, the compound was administered orally to female B6C3F1 mice at 300 mg/kg/day for 3, 5, 10, or 14 days. Body, liver, kidney, spleen, and thymus weights were measured. Selected hematological and bone marrow parameters were examined. Flow cytometric analysis was used to assess changes in lymphocyte subpopulations in the thymus and spleen, and production of antibody-forming cells in vitro was measured. Major effects included decreased thymus weight at all time points; increased spleen weight after 10 or 14 days of exposure, increased bone marrow cellularity after 10 or 14 days of exposure, significant decreases in mature lymphocyte subpopulations which were greater in the thymus than in the spleen, relatively selective depletion of the major subpopulation of thymocytes (CD4+CD8+), and decreased body weight. Overall patterns of changes were consistent with the conclusion that SMD rapidly depletes most CD4+CD8+ thymocytes, more slowly depletes a smaller number of mature lymphocytes in the thymus and spleen, and induces compensatory and/or detoxication mechanisms after 10-14 days of exposure. Subsequent experiments were done to assess selected immune function parameters. SMD at 50-300 mg/kg/day for 7 days caused substantial, dose-dependent suppression of NK cell activity. No suppression of antibody production in vivo or splenocyte responses to mitogens or allogeneic lymphocytes in vitro was detected. NK cell activity, thymus weight, and CD4+CD8+ thymocyte numbers were suppressed by dermal administration of SMD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601209 TI - Subchronic (13-week) toxicity studies of oral phenolphthalein in Fischer 344 rats and B6C3F1 mice. AB - Phenolphthalein is a cathartic agent that is widely used in over-the-counter laxatives. Thirteen-week toxicity studies of phenolphthalein were performed using F344/N rats and B6C3F1 mice. Rats and mice were fed ad libitum with a NIH 07 diet containing 0; 3000; 6000; 12,000; 25,000; or 50,000 ppm phenolphthalein. On a milligram per kilogram body weight basis, rats and mice fed 50,000 ppm phenolphthalein ingested more drug than would be expected during human laxative abuse. Phenolphthalein produced little evidence of toxicity in rats. There was slightly lower weight gain among the 25,000 and 50,000 ppm groups. Treated rats showed elevated relative kidney weights (males only) and elevated absolute and relative liver weights at 12,000-50,000 ppm phenolphthalein. Rat serum bile acids were depressed early (Days 5 and 6) by phenolphthalein treatment. Several treatment-related toxic effects, however, were identified in mice who received more phenolphthalein per unit body weight than rats. Although there were no effects on body weight gain, elevated liver weights were noted in female mice receiving 6000-50,000 ppm phenolphthalein. The primary treatment-related findings that occurred during the mouse studies involved the reproductive and hematopoietic systems. Reproductive changes including depressed testis and right epididymal weights and sperm density, an elevated production of abnormal sperm, and morphologic alterations in seminiferous tubules occurred at all levels of exposure (3000-50,000 ppm). Hematopoietic changes included bone marrow hypoplasia (12,000-50,000 ppm), increased splenic hematopoiesis (males only; 25,000 and 50,000 ppm), and an elevated incidence of micronucleated erythrocytes (6000 50,000 ppm). PMID- 1601210 TI - Reversible inhibition of intercellular communication among cardiac myocytes by halogenated hydrocarbons. AB - We examined the effect of 11 aliphatic halogenated hydrocarbons on the transfer of microinjected dye among cardiac myocytes from neonatal rats. Myocytes were suffused with increasing concentrations of halocarbon added as a 0.2% solution of dimethyl sulfoxide to M199 containing 1.8 mM Ca and 5% serum. Single cells were microinjected with the fluorescent probe Lucifer yellow (5% in 0.1 mM LiCl) and dye coupling to adjacent cells was monitored. All of the halocarbons tested exhibited a concentration-dependent inhibitory effect on intercellular communication that was reversible following washout of the compounds. Intercellular communication was blocked within 1 min of exposure to an effective concentration, and recovery of communication occurred even after 2 hr of exposure. Pretreatment of cells with SKF 525-A (25 microM) did not prevent the inhibition of intercellular communication by carbon tetrachloride suggesting an absence of P-450 involvement. EC50s were calculated for each chemical using probit analysis. A log-log comparison of the EC50s and the physicochemical properties of the chemicals demonstrated a high correlation (R2 = 0.933) between the EC50s and the octanol/water partition coefficients of the halocarbons. This suggests that incorporation of halocarbons in the membrane may block intercellular communication through modification of the immediate environment of the gap junctions. The results are in agreement with the hypothesis that inhibition of gap junctional communication is a factor in the arrhythmogenic effects of acute halocarbon exposure. PMID- 1601211 TI - Sex differences in monochloroacetate pretreatment effects on chloroform toxicity in rats. AB - Previous studies have shown that dichloroacetate and trichloroacetate increase the toxicity of CHCl3. The present experiments were designed to determine if monochloroacetate (MCA) similarly affects CHCl3 toxicity. There were occasional differences, but overall kidney function indices (urine volume, osmolality and electrolyte concentration, glucosuria, retention of urea nitrogen in plasma) were not affected differently at either 24 or 48 hr after CHCl3 in saline and MCA pretreated Sprague-Dawley rats of either sex. Males pretreated with MCA had 45 fold greater plasma alanine aminotransferase (ALT) compared to the saline pretreated group similarly dosed with CHCl3. ALT was increased threefold in female rats, a modest change that suggests hepatic damage, and BUN was nonsignificantly increased. Therefore hepatic and renal functions were assessed in females. MCA pretreatment did not alter the effects of CHCl3 on hepatic excretory function or glomerular or tubular function. Bile production and glomerular filtration were both decreased in the MCA group treated with peanut oil, suggesting that MCA impairs both liver and kidney function in female rats. MCA pretreatment increases CHCl3 hepatoxicity markedly in male rats and only slightly in female rats. This difference is likely due to the different effects, in males and females, of MCA on the cytochrome P450 isoforms that activate CHCl3. The effects of MCA on renal function in females would decrease CHCl3 delivery to kidney cells, suggesting that MCA may alter the distribution of CHCl3. PMID- 1601212 TI - Neuropathological effects of triphenyl phosphite on the central nervous system of the hen (Gallus domesticus). AB - The neurotoxic effects of single subcutaneous injections of 1000 mg triphenyl phosphite (TPP)/kg body weight were investigated in White Leghorn hens. At 7 days postexposure, birds began to show signs of mild to moderate ataxia that progressed to severe ataxia and paralysis at 21 days. Inhibition of whole brain neuropathy target esterase was 85% at 48 hr and 73% by 21 days postexposure. After postexposure periods of 7, 14, and 21 days, hens were killed and their brains and spinal cords were examined for degenerating axons and terminals using the Fink-Heimer silver impregnation method. A small amount of degeneration was noted at 7 days. By 21 days, dense degeneration was noted in the spinal gray matter and funiculi. Degeneration was also present in the granular cell layer of cerebellar folia I-VI and in nuclei and fiber tracts of the medulla. Moderate to dense degeneration was also seen in several forebrain and midbrain areas including the paleostriatum, ansa lenticularis, the dorso-intermediate thalamic nucleus, lateral spiriform, pedunculopontine tegmental, and lateral mesencephalic nuclei and in the deeper layers of the optic tectum. These results indicate that, in addition to affecting the spinal cord and brainstem, exposure to TPP also damages higher order centers responsible for processing and integrating sensorimotor, visual, and auditory information. PMID- 1601213 TI - A comparison of the acute toxicity, neuropathology, and electrophysiology of N,N diethyl-m-toluamide and N,N-dimethyl-2,2-diphenylacetamide in rats. AB - The insect repellent DEET and the structurally related herbicide diphenamid both cause ataxia associated with a spongiform myelinopathy largely confined to the cerebellar roof nuclei. This local myelinopathy was accompanied by the formation of neuronal cytoplasmic clefts and was produced by a single dose of 1 to 3 g/kg N,N-diethyl-m-toluamide (DEET). These dose levels also produced a severe and often fatal prostration and clear electrophysiological signs of prolonged suppressed seizure activity. Diphenamid produced an identical myelinopathy after doses of 0.8 to 1.5 g/kg but without the severe prostration, suppressed seizures, or neuronal clefts. The effects of diphenamid were shown to be reversible over 3 to 7 days by neuropathological, motor, and auditory evoked response indices. Both compounds caused characteristic changes in auditory evoked response which may be useful in clinical diagnosis. Six other alkyl amides, two of which produce signs of CNS excitation, failed to produce myelinopathy at the maximum tolerated doses. Our findings show close parallels with a number of human cases of DEET poisoning and indicate that other amides, like diphenamid, also pose a potential hazard. PMID- 1601214 TI - Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (OECD): familiarization using cyclophosphamide. AB - A familiarization study was conducted on the "Combined Repeat Dose and Reproductive/Developmental Toxicity Screening Test (ReproTox)" proposed by the OECD. Cyclophosphamide (CP) at doses of 6.7, 4.5, 3, 2, and 0 mg/kg body wt was given daily by gavage to groups of 12 male and 12 female Sprague-Dawley rats. As a result, anemia and leukopenia were evident in treated males. The absolute and relative thymus and spleen weights were decreased in treated rats. Histopathologically, atrophy of the thymus, spleen, and bone marrow was observed. With respect to the reproductive/developmental toxicity, dose-dependent increases in postimplantation loss of fetuses and postnatal death were found in dams given CP. The body weight of pups treated with CP was significantly lowered in a dose related manner. Thus the results demonstrated most of the known toxicological properties of CP, except the adverse effects on spermatogenesis and fertility. Therefore ReproTox can be considered as a useful screening test for assessing repeat dose and reproductive/developmental toxicity of existing chemicals of high production volume. PMID- 1601215 TI - Evaluation of teratogenic potential of N-formylpiperidine in rats. AB - The teratogenic potential of a versatile solvent, N-formylpiperidine (NFP), was evaluated in the rat. Three groups of 25 mated female Sprague-Dawley rats were given 110, 220, or 440 mg/kg/day NFP in distilled water by gavage on Days 6 through 20 of gestation. A control group of 25 animals received distilled water on a comparable regimen. Maternal animals were observed daily for signs of toxicity; body weights and food consumption were measured at regular intervals throughout the study. All animals were euthanized on Gestation Day 21 and the fetuses examined for cleft palate and external abnormalities. One-half of the fetuses in each litter were examined for visceral anomalies while the remaining fetuses were examined for skeletal malformations after appropriate staining. One female in the high dosage group died on Gestation Day 12. Clinical signs of toxicity, observed in 6 females in the high dosage group, included tremors, convulsive movements, and an apparent weakness of the legs. Maternal toxicity, in terms of significantly decreased body weight and food consumption, was observed in the mid and high dosage groups. Food consumption was also significantly depressed for the first 4 days of dosing in the low dosage group. There was a significant increase in number of resorptions in the high dosage group when compared to controls. No effects were observed on other reproductive parameters. Mean fetal body weight was significantly lower in the high dosage group when compared to controls. While the incidence of fetal malformations on a litter basis was higher in the high dosage group, this change was not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601216 TI - Assessment of exposure to pulmonary toxicants: use of biological markers. PMID- 1601217 TI - Time course of permeability changes and PMN flux in rat trachea following O3 exposure. AB - Changes in rat tracheal epithelial permeability and polymorphonuclear leukocyte (PMN) populations during a 24-hr time period following a 3-hr exposure to 0.8 ppm ozone (O3) were investigated. An increase in permeability to 99mTc-diethylene triaminepentaacetate (DTPA) occurred immediately after the exposure, peaked at the 8-hr time point and decreased to control level by 24 hr. For correlation with tracheal permeability, tracheal cross sections were stained with naphthol AS-D chloroacetate and PMNs were scored by their location as well as staining characteristics (positive or negative). The total PMN population remained at the control value at the 0-, 4-, and 8-hr time points, and increased at 12 hr, followed by a rapid decline to below the control value for the remaining time points. There was a shift at the 8-hr time point in the population location, from the vasculature to the interstitium, which returned to control values at 12 hr. The percentage stained PMNs increased significantly at 16 hr while remaining at control values for all other time points. The data reveal that there is a significant increase in tracheal epithelial permeability immediately after the exposure, but the overall increase in the PMN population is preceded by a lag phase. A decrease in the vascular pool of PMNs concomitant with an increase in the interstitial pool of PMNs suggests their migration from blood to the interstitium after ozone exposure. These data indicate that while PMNs may play a role in permeability changes of tracheal epithelium, the initiation is most likely due to other factors. PMID- 1601218 TI - Control of the nephrotoxicity of cisplatin by clinically used sulfur-containing compounds. AB - Several clinically used sulfur-containing compounds were examined as potential antagonists for the nephrotoxicity of cis-platin in Sprague-Dawley rats. The compounds studied were biotin, captopril, cefoxitin, cephalexin, the sodium salt of penicillin G, sulfathiazole, and thiamine hydrochloride. Biotin, captopril, cephalexin, and sulfathiazole were found to have a significant effect in reducing the nephrotoxicity of cisplatin when administered simultaneously with cisplatin via an intravenous route in the rat. Biotin was the most effective in providing renal protection and sulfathiazole the least effective, based upon BUN, serum creatinine values, and weight changes, though all four of these compounds provided a considerable measure of protection against the typical cisplatin induced nephrotoxicity. The effect of the simultaneous administration of cisplatin with biotin, cephalexin, and sulfathiazole was examined on the antitumor activity of cisplatin toward the L1210 murine leukemia in the DBA/2 mouse and the Walker 256 carcinosarcoma in the rat. With the L1210 murine leukemia no loss of antitumor activity was found for any of the compounds. With the Walker 256 carcinosarcoma some loss of antitumor activity was found with biotin. Both biotin and sulfathiazole are shown to be promising candidates for use in the suppression of the adverse effects of cisplatin, and other sulfur containing compounds currently in clinical use may have equivalent or superior properties in this respect. PMID- 1601219 TI - Acrylamide: dermal exposure produces genetic damage in male mouse germ cells. AB - Acrylamide is used extensively in sewage and wastewater treatment plants, in the paper and pulp industry, in treatment of potable water, and in research laboratories for chromatography, electrophoresis, and electron microscopy. Dermal contact is a major route of human exposure. It has been shown that acrylamide is highly effective in breaking chromosomes of germ cells of male mice and rats when administered intraperitoneally or orally, resulting both in the early death of conceptuses and in the transmission of reciprocal translocations to live-born progeny. It is now reported that acrylamide is absorbed through the skin of male mice, reaches the germ cells, and induces chromosomal damage. The magnitude of genetic damage appears to be proportional to the dose administered topically. PMID- 1601220 TI - Developmental toxicity of CI-921, an anilinoacridine antitumor agent. AB - CI-921, an anilinoacridine compound active against leukemic and solid tumors, was evaluated for potential developmental toxicity. Intravenous injections of CI-921 in dextrose were given to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg) on Gestation Days (GD) 6-15 and to female New Zealand White rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6-18. Appropriate vehicle and untreated controls were included. Maternal and fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Treatment of rats with 1.0 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain and food consumption during and after treatment. Reduced fetal body weight, an increased incidence of stunted fetuses, malformations of the axial and appendicular skeleton, microphthalmia, and an increased number of anatomical variations (including anomalies of the axial skeleton and apparent hydronephrosis) also occurred in rats at 1.0 mg/kg. Treatment of rabbits resulted in no apparent maternal toxicity. However, reduced fetal body weight, agenesis of the azygous lobe of the lung, and an increased incidence of variations of the axial skeleton occurred at 2.0 mg/kg in rabbits. These results indicate that CI-921, at the highest dose tested in each species, produced developmental toxicity in the presence of maternal toxicity in rats, but in the absence of maternal toxicity in rabbits. PMID- 1601221 TI - Comparative metabolism of methyl parathion in intact and subcellular fractions of isolated rat hepatocytes. AB - Metabolism of the widely used insecticide methyl parathion by isolated hepatocytes and various subcellular fractions was compared to determine the effects of cellular integrity on the metabolic profile observed. A reverse-phase ion-pair high-performance liquid chromatographic method was developed to separate and quantify methyl parathion and six of its hepatic biotransformation products: methyl paraoxon; desmethyl parathion; desmethyl paraoxon; p-nitrophenol; p nitrophenyl glucuronide; and p-nitrophenyl sulfate. Most compounds exhibited linear responses and limits of detection below 1 nmol. The chromatographic method was used to determine metabolic profiles of methyl parathion in isolated rat hepatocytes, sonicated hepatocytes, postmitochondrial fraction, microsomes, and cytosol. Isolated hepatocytes produced significantly more desmethyl parathion and p-nitrophenyl sulfate than the subcellular preparations, demonstrating that cellular integrity significantly affects the quantitative metabolic profile observed. PMID- 1601222 TI - Two-generation reproduction study of hydrotreated shale oil vapors. AB - Two generations of Sprague-Dawley rats were each exposed to vapors generated by countercurrent distillation (50 degrees C) at 0, 0.5, 2.5, and 5.0 mg/liter, for 6 hr/day, 5 days/week, for 124-126 days prior to mating. After mating, exposure was continuous except for the last day of gestation through lactation for F0 dams, and the last day of gestation through Day 6 of lactation for F1 dams. F1 pups were not exposed during lactation; F2 pups were exposed via nursing only. Body weights were recorded weekly before mating; organ and body weights were recorded on Days 1, 13, and 30 of gestation and on Days 1, 4, and 21 of lactation. Histopathology, reproductive performance, and certain sperm parameters were evaluated. The test material significantly (p less than 0.05) depressed body weights of F0 males and brain and lung weights of F1 weanling males at 5.0 mg/liter. Testicular weights of F1 weanling males were depressed at the 0.5 and 5.0 mg/liter concentrations. While a dose-related decrease in sperm count and sperm ATP levels and an increase in ATP/sperm ratios were observed in F0 males at 2.5 and 5.0 mg/liter, there was no adverse effect on overall reproductive performance. PMID- 1601223 TI - Reproductive toxicity evaluation of acetaminophen in Swiss CD-1 mice using a continuous breeding protocol. AB - Acetaminophen (APAP) was evaluated for reproductive toxicity in Swiss CD-1 mice using a continuous breeding protocol. APAP was administered in the diet at 0, 0.25, 0.5, and 1.0% (w/w), which represented average daily intakes of 0, 357, 715, and 1430 mg APAP/kg/day, respectively. Exposure of parental (P) breeding pairs to 1% APAP in the diet for 14 weeks during cohabitation significantly decreased the number of litters per pair, and reduced, although not significantly, the number of live pups per litter. Importantly, 6 of 19 high-dose P pairs failed to produce a fifth litter, and this fully accounted for the diminished number of litters in this group. In addition, the fifth litter that was produced by the 13 high-dose P pairs averaged only about 9 live pups per litter, which correspondingly reduced the overall group average for this parameter. In comparison, the control and two lower-dose P pairs produced 11 or 12 live pups per litter on average. Although the birth weights for F1 pups in the final litter were unaffected by prenatal APAP exposure, postnatal growth was adversely affected as evidenced by retarded weight gain as measured at 28 and 74 +/- 10 days of age for all three dietary levels. At 1% APAP this weight gain effect was more pronounced at Day 28 than at Day 74 +/- 10, suggesting that nursing pups may have been exposed to higher concentrations or may be more sensitive to APAP and/or an active metabolite than were the young adults.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601224 TI - 2,4,5-trichlorophenoxyacetic acid influence on 2,6-dinitrotoluene-induced urine genotoxicity in Fischer 344 rats: effect on gastrointestinal microflora and enzyme activity. AB - 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T) and 2,6-dinitrotoluene (2,6-DNT) are hazardous chemicals that have potential harmful effects. 2,6-DNT is recognized as a hepatotoxicant while 2,4,5-T, a component of Agent Orange, is also suspect. 2,6 DNT requires both oxidative and reductive metabolism to elicit genotoxic effects. To determine what effect 2,4,5-T had on 2,6-DNT metabolism, intestinal enzymes, microbial populations, and urine mutagenicity were examined during 2,4,5-T treatment. Weanling Fischer 344 male rats were treated daily with 54.4 mg/kg 2,4,5-T by gavage for 4 weeks. One, two, and four weeks after the initial 2,4,5-T dose, rats were administered (po) 2,6-DNT (75 mg/kg) and urine was collected for 24 hr in metabolism cages. Azo reductase, nitroreductase, beta-glucuronidase, dechlorinase, and dehydrochlorinase activities were examined concurrently. Treatment of rats for 1 week reduced the transformation of 2,6-DNT to mutagenic urinary metabolites. This was accompanied by a decrease in the fecal anaerobic microorganisms. The elimination of Lactobacillus fermentum from the small intestine and cecum of treated animals accompanied a significant increase in oxygen-tolerant lactobacilli and other unidentified aerobic microorganisms. However, there were no significant alterations in the intestinal enzyme activities examined. By 2 weeks of 2,4,5-T treatment, microbiota and urine genotoxicity returned to the levels observed in control animals. This trend continued for the duration of the experiment. After 2 weeks, while cecal nitroreductase and azo reductase activities increased, small intestinal beta glucuronidase activity decreased. By 4 weeks, treated and untreated animal intestinal enzyme activities were indistinguishable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601225 TI - Three-month effects of MDL 19,660 on the canine platelet and erythrocyte. AB - Nine male and nine female Beagle dogs were divided into three groups and administered orally 0, 15, or 30 mg/kg/day of the antidepressant compound MDL 19,660(5-(4-chlorophenyl)-2,4-dihydro-2,4-dimethyl-3H-1,2,4-triazole-3-t hione) for 3 months to determine the long-term effects on hemopoietic cells. Compared to a control platelet range of 353,000-452,000/microliters, a thrombocytopenia reached lowest mean levels of 135,000/microliters in the 15 mg/kg/day dogs after 2 weeks and 81,000/microliters in the 30 mg/kg/day dogs after 1 week. Subsequently, platelet numbers progressively increased and by the end of the study averaged 222,000/microliters and 203,000/microliters in dogs administered 15 and 30 mg/kg/day. Ultrastructural study of the platelet increase in the 30 mg/kg/day dogs revealed more smaller discoid platelets but no change in percentage platelets with vacuolar degeneration. Histologically, megakaryocyte hyperplasia was present in the sternal marrows and spleens of treated dogs. These observations suggest that increased thrombopoiesis rather than reduced destruction was involved in this partial recovery of platelet numbers during continuous treatment. Concurrently, cyclic formation of reticulocytes and Heinz bodies occurred in dogs given 30 mg/kg/day of MDL 19,660. These dogs had slightly lower erythrocyte counts, hemoglobin levels, and hematocrits in association with hemosiderosis (spleen, liver), extramedullary hematopoiesis (spleen), and bone marrow hypercellularity. These findings indicate that both destructive and regenerative processes followed MDL 19,660-induced Heinz body formation. PMID- 1601226 TI - Evaluation of the potential for developmental toxicity in rats and mice following inhalation exposure to tetrahydrofuran. AB - Sprague-Dawley rats and Swiss (CD-1) mice were exposed to 0, 600, 1800, or 5000 ppm THF (a four-carbon cyclic ether, widely used as an industrial solvent) vapors, 6 hr/day, 7 days/week (6-19 days of gestation (DG) for rats; 6-17 DG for mice). Body weights of pregnant rats in the 5000 ppm group were reduced at euthanization. There were no effects on the percentage of live rat fetuses/litter or on the fetal sex ratio. Fetal body weight was significantly reduced for the 5000 ppm group, but the incidence of abnormalities was not increased. Mice in the 1800 and 5000 ppm groups were sedated during exposure; approximately 27% of the mice in the 5000 ppm group died. Mean body and uterine weights of mice were reduced for the 1800 and 5000 ppm groups at euthanization (18 DG), but adjusted maternal weight gain was not affected at 1800 ppm. There was a reduction in the percentage of live fetuses/litter for the mice in 1800 and 5000 ppm groups (95% resorptions in the 5000 ppm group). Fetal weight and sex ratio in mice were not affected. An increase in the incidence of reduced sternebral ossifications was correlated to THF concentration, although differences between groups were not statistically significant. There were no increases in the incidences of other malformations or variations. These results suggest that THF may be embryotoxic in mice, but if the conceptus survives, development as assessed by this experimental design continues in a normal fashion. The no-observable-adverse-effect level (NOAEL) for maternal toxicity was 1800 ppm in both rats and mice. The NOAEL for developmental toxicity was 1800 ppm in rats and 600 ppm in mice. PMID- 1601227 TI - Developmental toxicity of boric acid in mice and rats. AB - Boric acid (BORA), an ingredient of many cosmetics, pharmaceuticals, and pesticides, was tested for developmental toxicity in timed-pregnant Swiss mice and Sprague-Dawley rats (n = 26-28/group). BORA (0, 0.1, 0.2, or 0.4% in feed) was provided throughout gestation to attain steady-state exposure as early as possible during prenatal development. Average doses (mg/kg/day) were 248, 452, or 1003 in mice, and 78, 163, or 330 in rats. To limit prenatal mortality, BORA (0.8% or 539 mg/kg/day) was provided to an additional group of rats on Gestational Days (GD) 6 to 15 only. On GD 17 (mice) or 20 (rats), fetuses were weighed and examined for malformations (external, visceral, skeletal). Mouse dams exhibited mild renal lesions (greater than or equal to 0.1%), increased water intake and relative kidney weight (0.4%), and decreased weight gain (0.4%) during treatment. There was a reduction of fetal body weight (greater than or equal to 0.2%) and an increased incidence of resorptions and malformed fetuses per litter (0.4%). Morphological changes included an increased incidence of short rib XIII (a malformation) and a decreased incidence of rudimentary or full rib(s) at lumbar I (an anatomical variation). Maternal rats exhibited increased liver and kidney weights at greater than or equal to 0.2%, altered water and/or food intake at greater than 0.2%, and decreased weight gain at greater than 0.4%. Average fetal body weight/litter was reduced at all doses. Prenatal mortality was increased only at 0.8%. The incidence of fetal malformations was significantly increased at greater than or equal to 0.2%. The most frequently observed malformations were enlarged lateral ventricles of the brain and agenesis or shortening of rib XIII. In rats, the no-observable-adverse-effect level (NOAEL) for maternal toxicity was 78 mg/kg (0.1%), while in mice the low dose of 248 mg/kg (0.1%) approached the maternal NOAEL with mild renal lesions in only 2 of 10 females. Embryo/fetal toxicity occurred in all groups of rats at greater than or equal to 78 mg/kg (greater than or equal to 0.1%) while the NOAEL for developmental toxicity in mice was 248 mg/kg (0.1%). Thus developmental toxicity occurred below maternally toxic levels in rats as well as in the presence of maternal toxicity in mice and rats. PMID- 1601228 TI - Sequential study of the chronic nephrotoxicity induced by dietary administration of ethoxyquin in Fischer 344 rats. AB - Groups of 3-week-old male and female Fischer 344 rats were administered 0.5% ethoxyquin-containing diet for varying periods of time, ranging from 4 weeks up to 18 months, to assess renal histopathology. The primary lesion observed was renal papillary necrosis in the male rat, commencing as interstitial degeneration of the papillary tip by 4 weeks exposure, and reaching a complete form of papillary necrosis by 24 weeks. The papillary necrosis in male rats was consistently accompanied by active pyelonephritis affecting the cortex, and urothelial hyperplasia in the renal pelvis. A marked sex difference was evident in that female rats developed papillary change at a later stage than males and the lesion never progressed beyond interstitial degeneration. A further sex difference associated with ethoxyquin treatment was the increasing cellular accumulation of lipofuscin-related pigment involving proximal tubules in female rats. Spontaneous chronic progressive nephropathy (CPN) was exacerbated by ethoxyquin in both males and females, but more so in the former. Proximal tubule hyperplasia was most frequently observed in ethoxyquin-treated males at the later sampling times. In all cases, such proliferative lesions were associated either with pyelonephritis or with the most advanced stages of CPN. Contrary to a previous report, there was no evidence that ethoxyquin directly induced preneoplastic renal tubule hyperplasia. PMID- 1601229 TI - Developmental effects of methyl benzimidazolecarbamate following exposure during early pregnancy. AB - Methyl 2-benzimidazolecarbamate (MBC) and its parent compound benomyl are used as agricultural fungicides. Both chemicals are embryotoxic if administered during organogenesis, and benomyl is teratogenic. Based on a previous study indicating a lack of maternal effects of MBC following exposure during early pregnancy, the current experiments were designed to evaluate the effect of exposure to MBC during early pregnancy on developmental parameters of offspring. Rats were administered MBC at 0, 100, 200, 400, or 600 mg/kg/day during Days 1-8 of pregnancy and killed on Day 11 or Day 20 of gestation. On Day 11, embryos were assessed for survival rate, growth parameters, and anomalies. On Day 20, standard developmental toxicity evaluations were performed. Doses of 200 to 600 mg/kg/day MBC reduced embryonic survival by Day 11; exposure to MBC at 100 to 600 mg/kg/day reduced the number of fetuses surviving on Day 20. Evidence of developmental delay was apparent on Day 11 at all doses, and fetal weight was reduced by Day 20. MBC produced a dose-dependent increase in developmental defects seen on Day 11 and in several malformations observed on Day 20. MBC exposure during the first week of pregnancy was shown to be embryotoxic, resulting in embryonic death, growth retardation, and developmental abnormalities when evaluated on Days 11 or 20 of gestation. PMID- 1601230 TI - Topical anesthetic-induced methemoglobinemia in sheep: a comparison of benzocaine and lidocaine. AB - Benzocaine induces methemoglobin (MHb) in several species, whereas lidocaine may increase MHb in cats and human. Elevated MHb (greater than 20%) in sheep after benzocaine exposure was recently recognized. MHb decreases blood oxygen-carrying capacity which can complicate interpretation of experimental data. Sheep are used in research which requires tracheal intubation and blood gas analysis. Since benzocaine and lidocaine are used to provide local anesthesia prior to intubation, we compared MHb production by sheep after exposure to these drugs. A dose-response relationship between benzocaine and MHb was investigated. Eight crossbred Dorset ewes were dosed intranasally with benzocaine for 2 sec or with 40 mg of lidocaine in a randomized crossover design. Sheep with elevated MHb after the 2-sec benzocaine dose were later dosed with benzocaine intranasally for 10 sec. MHb levels were measured periodically on a CO-Oximeter. A quantitative MHb response to an indirect MHb former, p-aminopropiophenone (PAPP), by each sheep was determined 15 min after PAPP (0.6 mg/kg iv). MHb levels remained at baseline (1-2%) after lidocaine exposure in all sheep, as well as in four sheep (nonresponders) after the 2-sec benzocaine dose. Four sheep (responders) demonstrated 16.5-26.4% MHb after the 2-sec benzocaine dose. The responders formed 38.2-50.5% MHb after the 10-sec benzocaine dose. All responders developed high MHb after PAPP, while nonresponders developed slightly elevated MHb after PAPP. An N-hydroxy metabolite of benzocaine is the likely active MHb-forming substance. Benzocaine should be replaced by lidocaine when local anesthesia of the nasal or oropharyngeal region in sheep is required. PMID- 1601231 TI - Pharmacokinetic analysis of protection by an organophosphorus insecticide, chlorfenvinphos, against the toxicity of its succeeding dosage in rats. AB - We have previously reported that the acute oral toxicity of chlorfenvinphos (CVP) is reduced by the oral pretreatment of rats with the same compound. In this report, the mechanism of this protection was clarified mainly through the physiologically based pharmacokinetic analysis. The CVP pretreatment (15 mg/kg, po, 24 hr before) reduced the lethality of po CVP greatly, and that of iv CVP to a lesser extent. Brain acetylcholinesterase inhibition by po and iv CVP was also decreased by the pretreatment. The magnitude of reduction of the inhibition caused by the po CVP was greater than that of the iv CVP. The ratio of CVP concentration between the brain and plasma was the same, regardless of the route of administration or the pretreatment. The pretreatment greatly reduced the plasma concentration and the area under the plasma concentration versus time curve (AUC) of the po CVP, but did not change appreciably that of the iv CVP. The unbound fraction of CVP in the blood or the liver was not changed by the pretreatment. According to physiologically based pharmacokinetic analysis, the decrease in AUC of the po CVP may be mainly caused by an increase in intrinsic clearance of the liver and a decrease in the partition coefficient of CVP between the emergent blood and the liver. The increase in the intrinsic clearance may be related to the metabolic induction observed in vitro. The pretreatment decreased the absorption rate constant of the po CVP. This change in combination with the above two factors which reduce AUC might be the reason for the decrease in the plasma concentration after the po CVP, and the protection against the CVP toxicity of the succeeding dosage. PMID- 1601232 TI - Respiratory and cardiovascular changes associated with toxic doses of a peptide antagonist of vasopressin in the rat. AB - SK&F 101926 is a synthetic octapeptide which was designed to promote free water excretion by antagonizing the action of antidiuretic hormone. The clinical and pathologic changes in rats resulting from lethal doses of SK&F 101926 have suggested that death is associated with respiratory failure and/or cardiovascular collapse. To define the relationships between respiratory failure, cardiovascular collapse, and death, respiratory and cardiovascular parameters were monitored in anesthetized rats following the intravenous administration of SK&F 101926 at a dosage (3 mg/kg) which resulted in 70% mortality. Within 5 min after receiving this dosage, mean arterial blood pressure was reduced to values between 30 and 40 mm Hg in all rats. This degree of hypotension was well tolerated by some rats and, consequently, was not considered to be the cause of death. Deaths occurred between 9 and 58 min after dosing and were preceded by respiratory depression involving marked reductions in respiratory rate and the lack of compensatory increases in tidal volume. At the time of respiratory arrest, heart rates remained above 200 beats/min, mean arterial blood pressure remained between 30 and 40 mm Hg, and there were no consistent changes in dynamic lung compliance or total pulmonary resistance. Pretreatment of rats with a mast cell stabilizing agent (disodium cromoglycate), a mast cell degranulating agent (compound 48/80), or a histamine/5-hydroxytryptamine blocking agent (cyproheptadine) prevented the reductions in respiratory rate and death caused by SK&F 101926. These pretreatments also reduced the effect of SK&F 101926 on blood pressure, but were not able to completely prevent the hypotension.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601233 TI - Further support for the nonrotational system. PMID- 1601234 TI - Guidelines for the diagnosis and management of asthma. PMID- 1601235 TI - Patient gender and cancer screening. PMID- 1601236 TI - Identifying and supporting battered women: if not now, when? PMID- 1601237 TI - Life's stories: her eyes and my glasses. PMID- 1601238 TI - Family physicians' approach to wife abuse: a study of Ontario, Canada, practices. AB - BACKGROUND: Approximately one in eight Canadian women is assaulted by a male partner during the course of their relationship. The objective of this research was to determine the perceptions of Ontario family physicians regarding their effectiveness in identifying and dealing with abused female patients. METHODS: A questionnaire was mailed to all family physicians in one urban and two rural Ontario communities. The questionnaire requested information about the physicians' perceptions regarding: 1) success in identifying wife abuse, 2) barriers to identifying wife abuse, and 3) the physician's role in management of abused patients. RESULTS: The response rate was 82%, yielding a sample of 505 physicians. Respondents estimated that 14% to 17% of their female patients had been victims of abuse, but more than 70% of respondents believed that they identified fewer than 50% of such patients in their practices. The most common reasons cited for failing to detect abused women were patient unresponsiveness, lack of physician initiative, and infrequent visits by the patient. Respondents indicated that the most important role of a family physician in managing abused patients was to provide emotional support, inform patients about community services, and arrange referrals for those services. CONCLUSION: Despite knowledge of its prevalence, physicians underdiagnose spouse abuse. This suggests a need for more physician education. PMID- 1601239 TI - Prevalence of domestic violence in community practice and rate of physician inquiry. AB - BACKGROUND: National surveys show that each year in the United States approximately 2 million women are battered by their husbands. Only a small percentage of these women are identified by physicians. The objective of this research was to determine the incidence and prevalence of spouse abuse among women seeking health care in a family practice clinic (or setting). METHODS: During a two-month period, all adult women seeking health care from a family practice clinic in a medium-sized Midwestern community were asked to complete an anonymous questionnaire about whether they had ever been physically assaulted by their partners. RESULTS: Of 476 consecutive women seen in practice, 394 (82.7%) agreed to participate. Of these, 22.7% had been physically assaulted by their partners within the last year. The lifetime rate of physical abuse was 38.8%. Only six women in the sample had ever been asked about abuse by their physician in a recent visit [corrected]. CONCLUSIONS: Although spouse abuse is common, physicians rarely ask about it. Physicians should be trained to detect and assess abuse among female patients. PMID- 1601240 TI - Teaching family-centered perinatal care in family medicine, Part I. AB - Pregnancy, childbirth, postpartum, and infant care are a continuum in the family life cycle for which the family physician is especially qualified to provide primary, comprehensive care. The purpose of this paper is to document and share the controversies, wisdom, and knowledge about caring for women and their families before, during, and after pregnancy. Family physicians can be leaders in developing an appropriate perinatal care system for the community. The level of care the family physician chooses to provide is discretionary. However, the family physician should be invested in ensuring that all families receive the greatest benefit from pregnancy, birth, and the newborn experience. Interest in perinatal care in family medicine is increasing, as reflected by the growing numbers participating in the Society of Teachers of Family Medicine Working Group on Family-Centered Perinatal Care. The authors of this article, who are active in this working group, hope that this information is useful in designing a balanced curriculum and delivery system for perinatal care in family medicine training programs. PMID- 1601241 TI - Creating a substance abuse network in family medicine: lessons learned. AB - Family practice was one of several primary care specialties awarded federal contracts in 1985 to survey substance abuse training needs. Family medicine has since excelled in creating a viable substance abuse network. Key events were the sponsorship of a fellowship program, the formation of the Society of Teachers of Family Medicine (STFM) Substance Abuse Working Group, and the working group's pursuit of externally funded projects. Tangible measures of the network's success include collective funding exceeding $7.3 million, an increase in the number of substance abuse activities at annual STFM conferences, and a nearly four-fold growth in the group's membership and collaborative publications. Key factors underlying the vitality of the network that may be generalizable include: 1) initial emphasis on training family physician faculty; 2) making optimal use of the existing administrative channels within STFM; 3) acquisition of external funding; 4) some continuity of core persons working together; 5) active networking within and outside family medicine; and 6) promotion of individual success. PMID- 1601242 TI - A cross-sectional analysis of family medicine publications in the indexed medical literature. AB - BACKGROUND: Publications are important to the academic development of the field of family medicine. Not all manuscripts written by family physicians or family medicine faculty are published in family medicine journals. The purpose of this study was to determine where manuscripts generated by US family medicine department faculty are being published. METHODS: A MEDLINE search was performed for all English language articles published in 1979 and 1989. The search technique involved identifying articles that included the words "family" and "medicine" or "family" and "practice" in the institution field of the MEDLINE index. All identified articles were then manually reviewed to confirm authorship by family medicine department faculty. Article types were classified according to previously published schemata. RESULTS: The research identified 178 articles from 1979 and 328 articles form 1989. In 1979, 52% of the articles had been published in family medicine journals. In 1989, the percentage was exactly 50%. Biomedical articles comprised the largest category (approximately half) of articles. Educational articles were the second most common type. CONCLUSIONS: The number of publications generated by family medicine faculty has grown, as has the number (but not the percentage) of articles published in non-family medicine journals. PMID- 1601243 TI - A comparison of initial and established patient encounters using the Davis Observation Code. AB - BACKGROUND: Previous research has evaluated how communication during medical visits affects patient outcomes such as compliance, recall, and satisfaction. These prior studies generally did not control for new versus established patient visits. The objective of the present research was to explore differences between new and established patient encounters. METHODS: This research studied 62 new patient and 58 established patient encounters to a university-based family practice clinic. The Davis Observation Code was used to code and evaluate the encounters. RESULTS: Established patient encounters were shorter and involved more chatting, counseling, discussions of treatment effects, compliance checking, and requests for specific patient behavior changes regarding health promotion. On the other hand, established patient encounters involved less structuring of the interaction with the patient, less history taking, and fewer discussions regarding family information, smoking, and substance abuse. CONCLUSIONS: The results indicate that what takes place during the medical interview is highly dependent on physician-patient familiarity. Future research on physician-patient interactions should consider whether the interactions represent new or established visits. PMID- 1601244 TI - A family practice model of health care for homeless people: collaboration with family nurse practitioners. AB - The growth of a large population of people without permanent housing in the United States has brought with it the necessity to address the unmet health needs of this group. As homelessness spreads, its demographic pattern has become more heterogeneous, with young vulnerable families now the major subgroup. This paper explores issues of homelessness in Westchester County, N.Y., which, despite being the 10th richest county in the United States, has the highest per capita homeless rate in the state. Children younger than age 18 represent the majority of this group. Barriers to the delivery of health care services are described, including fragmented life-styles, lack of insurance, insensitivity of care givers, distance from services, and inflexibility of traditional sources of health care. A model that has been developed for delivery of services is discussed. This model, the Outreach Health Care Unit, is run by nurse practitioners in collaboration with family physicians and is centered at the site of social service activities for homeless families and single men in Yonkers, N.Y. It is a collaborative endeavor of a nursing school, community hospital family practice residency program, and a network of social service agencies. The use of this model for education and research is also discussed since the goal is to provide both health services and training for health care providers. PMID- 1601245 TI - Voices from family medicine: Ian McWhinney. Interview by John J. Frey and William B. Ventres. AB - Ian McWhinney is one of the most widely respected philosophers and investigators in medicine. He has received numerous awards from academic societies--among them the Curtis Hames Award and the Certificate of Excellence from the Society of Teachers of Family Medicine--has been appointed a Member of the Institute of Medicine of the National Academy of Sciences in the United States, has been awarded an honorary MD by the University of Oslo, and has had a long career of publication and teaching in countries all over the world. In 1968, he became first the professor and chair of family medicine in Canada, at the University of Western Ontario. During his career, he has constantly explored the meaning of medical practice for both physicians and patients. His writing has influenced generations of scientists in family medicine and beyond. This transcript is an abridged and edited version of interviews with Dr. McWhinney in May 1991 and February 1992. PMID- 1601246 TI - GNA announces changes in continuing education. PMID- 1601247 TI - Towards a definition of community. PMID- 1601248 TI - Futurebound nurses: nursing as we know it will not survive in the next decade. Interview by Mary Ann Camann. PMID- 1601249 TI - Nicotine: this country's real drug epidemic. PMID- 1601250 TI - Morphometric analysis of small follicles in the ovary of the musk shrew (Suncus murinus L.) at different ages. AB - On the basis of morphological characteristics of granulosa cells surrounding the oocyte, the small follicles (Class 1) in the ovary of the musk shrew were classified into four groups: Type B (flattened cells), Type B/C (mixture of flattened and cuboidal cells), Type C (single layer of cuboidal cells), and Type D (more than one to two layers of cuboidal cells without epitheloid cells in the theca). The pattern of small follicular development was characterized by a short early dormant followed by a rapid growth phase. Initiation of follicular growth commenced at intermediate stage between large Type B and Type B/C follicles. Types B, B/C, and C were present in the ovary on Day 0 after birth, whereas Type D first appeared on Day 3 after birth. The total population of small follicles and the number of each type of follicle decreased with increasing age. In all age groups investigated, the total number of small follicles and the number of follicles of Types B, B/C, and C in the left ovary were significantly higher compared with those in the right ovary. The percentage of Type B follicles decreased with increasing age, while the percentages of Types B/C, C, and D increased. A positive correlation between the percentage of Type B and a negative correlation between the percentages of Types B/C, C, and D and the total small ovarian follicular population indicate the operation of an intraovarian regulation of some early steps of follicular growth. PMID- 1601251 TI - Identification and purification of a high-affinity thyroxine binding protein that is distinct from albumin and prealbumin in the blood of a turtle, Trachemys scripta. AB - Fractionation of plasma proteins in the turtle, Trachemys scripta, confirmed the presence of a high-affinity thyroxine (T4) binding protein (TBP) that was distinct from albumin (ALB) and prealbumin (PA). The TBP was isolated by adsorption on a T4-affinity column and a high degree of purification was achieved by gel filtration and preparative electrophoresis. Analysis by reversed-phase HPLC showed a single peak of protein with T4 binding activity. The electrophoretic mobility of the TBP, based on staining and binding to [125I]T4 on nondenaturing polyacrylamide gels (PAGE), corresponded to that of the major T4 binding activity previously identified in plasma (ca. 60 kDa). PA was fractionated as a complex with retinol binding protein (PA-RBP) based on retinol associated fluorescence using ion exchange chromatography on DEAE-Sephacel and gel filtration. This complex behaved as a larger and more highly charged molecule than TBP; it was partially dissociated in low ionic strength basic solution. SDS PAGE of the PA-RBP-enriched fraction revealed a major component of about 48 kDa (possibly free PA), with smaller components corresponding to those expected for free RBP (ca. 22 kDa) and subunits of PA (e.g., 14 and 28 kDa). ALB was purified by ion exchange chromatography on DEAE and gel filtration; it behaved as less basic than PA with MW approximately 67 kDa. TBP accounted for virtually all the T4 binding activity of whole plasma: TBP was about 100 times as active and PA and ALB were less than 1% as active as plasma. The binding affinity of purified TBP was similar to that of whole plasma from turtle and human (e.g., approx. 10(9) M 1 on Sephadex G-25). PMID- 1601252 TI - Characterization of 3,5,3'-triiodothyronine receptors in primary cultures of hepatocytes and neurons from chick embryo. AB - We have detected the presence of nuclear 3,5,3'-triiodothyronine (T3) receptors in primary cultures of chick embryo hepatocytes and neurons. Hepatocytes were isolated from livers of embryos of 12, 16 and 19 days by treatment with 0.2% collagenase and hyaluronidase. They were plated at a density of 3-4 x 10(5)/35-mm petri dish in Ham's F-10 medium containing fetal calf serum, tryptose phosphate, and antibiotics. Cells were used for the binding assay at Day 3 of culture. Neurons from 8-day-old embryo brains were cultured in a serum-free medium at a density of 1.2 x 10(6) cells/35-mm petri dish and used for the binding assay after 7 days of culture. Biological activity of hepatocytes was determined by measuring insulin binding, inositol phosphate formation, and 5'-monodeiodinase activity. Neurons or glial cells in culture were identified by immunostaining with anti-neurofilaments and anti-glial fibrillary acidic protein antisera. Binding assay was performed with isolated nuclei and 0.4 M NaCl nuclear extracts. With the latter preparation, the Scatchard analysis showed, in both cells, a single, high-affinity, low-capacity T3 receptor. In the hepatocytes of 12-, 16-, and 19-day-old embryos association constants (Ka) were, respectively, 0.93 +/- 0.02, 0.74 +/- 0.03, and 0.56 +/- 0.04 nM-1, whereas the maximal binding capacities (MBC) were 2.26 +/- 0.2, 2.72 +/- 0.33, and 1.83 +/- 0.19 fmol/microgram DNA (mean +/- SE, n = 3). In neurons Ka was 1.25 +/- 0.53 nM-1 and MBC 0.59 +/- 0.14 fmol/microgram DNA (n = 3). The receptor had a sedimentation coefficient of 3.4 S, an estimated Mr of 59 kDa, and the following relative affinity for thyroid hormone analogues: TRIAC greater than L-T3 greater than L T4. These data indicate that cultured hepatocytes and neurons of chick embryo contained T3 receptors with properties similar to those described in intact tissues from this and other species. Only the MBC of neurons was 50% lower than that observed in whole brain of embryo, but was comparable to values observed in cultured neurons from other species. PMID- 1601253 TI - Cuticular hydrocarbons of Calliphora vomitoria (Diptera): relation to age and sex. AB - Changes in epicuticular hydrocarbon content and composition were examined from 3 to 120 hr postemergence in both sexes of Calliphora vomitoria. n-Alkanes and mono and dimethylalkanes with 20 to 31 carbon atoms were the major hydrocarbons detected. Alkenes were only detected in the females. Males had fewer hydrocarbons (40 versus 49 for the females). In males this number remained constant from 3 to 120 hr, whereas in females the number increased progressively from 3 to 48 hr. The males had a greater total of hydrocarbons than the females (x6 versus x3.5). They had significantly more hydrocarbons by 48 hr, the time of sexual maturation, while in females, the hydrocarbon content increased between 6 and 24 hr postemergence, just before the onset of previtellogenesis. Hydrocarbon synthesis continued up to 120 hr in males, but remained constant in the females after 24 hr. Hydrocarbon composition differed in males and females and between the young (3 and 6 hr) and the older animals (24 to 120 hr). The young animals were characterized by the presence of monomethylalkanes with chain lengths over 25C and the older animals by monomethylalkanes with chain lengths less than 25C. Alkenes were found only in females. The males were characterized by the presence of di- and monomethylalkanes with 23, 24, and 26 carbon atoms. PMID- 1601254 TI - Properties of common carp gonadotropin I and gonadotropin II. AB - Two gonadotropins, GtH I and GtH II, were extracted with 35% ethanol-10% ammonium acetate, pH 6.1, from female common carp pituitary glands and purified by ion exchange chromatography on a DE-52 column followed by gel filtration on a Sephadex G-75 column. Molecular weights of GtH I and GtH II as determined by SDS PAGE were 45,000 and 35,000, respectively. Both GtHs dissociate into two subunits following reduction with beta-mercaptoethanol. These subunits contain different N terminal amino acids (Tyr and Gly for GtH I; Tyr and Ser for GtH II). GtH I was acid stable and did not dissociate into subunits following treatment with 0.1% trifluoroacetic acid; GtH II readily dissociated into subunits by this treatment. GtH I and GtH II have distinct elution profiles on reverse-phase HPLC. The N terminal amino acid sequence of the beta-subunit of GtH II was identical to that of common carp maturational GtH described by other workers suggesting that GtH I is a newly identified molecule. This was supported by radioimmunoassay analysis. GtH II and a common carp maturational GtH preparation (F11 cGtH; Peter et al., 1982, J. Interdiscipl. Cycle Res. 13, 229-239) had similar immunological activity in tests with antisera to the beta-subunit of maturational GtH whereas GtH I had low (less than 6%) cross-reactivity. GtH I, GtH II, and F11 cGtH were equipotent in tests with antisera to the alpha-subunit of maturational GtH suggesting these molecules contain a similar alpha-subunit. In vitro bioassays using goldfish revealed that GtH I and GtH II share the same spectrum of biological activities causing stimulation of ovarian and testicular steroidogenesis and induction of oocyte final maturation. The demonstration of two chemically distinct GtHs in common carp is similar to what has been described for chum and coho salmon. PMID- 1601255 TI - Reproductive endocrinology of macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins. I. Seasonal changes in plasma levels of gonadal steroids and LH in breeding adults. AB - Changes in plasma luteinizing hormone (LH), testosterone, oestradiol, and progesterone were measured throughout the breeding and molt cycle in free-living male and female macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins, at Bird Island, South Georgia (54 degrees S, 38 degrees W). These two species are sympatric but have a markedly different breeding cycle. In macaroni penguins plasma levels of all hormones, except LH in males, were significantly elevated at the time of arrival at the breeding colony. In both species and sexes plasma LH, testosterone (males), and estradiol (females) levels were highest during nest-building and postcopulation, coincident with the period of frequent agonistic interactions in males and egg-formation in females. Elevated testosterone levels occurred in females of both species during the postcopulation period and may be associated behaviourally with both sexes being involved in nest defence. Male birds also had elevated estradiol levels. Following copulation, plasma levels of LH, testosterone, and estradiol decreased to basal levels in both sexes and species and, except for a transient increase in testosterone in male macaroni penguins, remained low through to the end of molt. There was no associated rise in LH or testosterone during premolt and early molt despite a further period of agonistic and social interaction, suggesting that birds were in a photorefractory state at this time. Plasma progesterone showed a pattern of variation different from that of the other hormones. In both species and sexes, plasma levels were elevated between arrival and early chick-rearing and then decreased slowly to low levels during molt. PMID- 1601256 TI - Reproductive endocrinology of macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins. II. Plasma levels of gonadal steroids and LH in immature birds in relation to deferred sexual maturity. AB - Plasma levels of LH, testosterone, estradiol, and progesterone were measured, during the breeding season, in adult and immature macaroni (Eudyptes chrysolophus) and gentoo (Pygoscelis papua) penguins, at Bird Island, South Georgia (54 degrees S, 38 degrees W), in relation to deferred sexual maturity. Macaroni penguins do not breed until 6-8 years of age whereas gentoo penguins first breed at 2 years of age. Plasma LH was elevated in 3- to 5-year-old macaroni penguins, but not in 1- to 2-year-old birds nor 1-year-old gentoos. However, 1 year olds of both species responded to an injection of exogenous LH-RH by increasing LH secretion. Some individual 3-, 4-, and 5-year-old macaroni penguins had circulating testosterone levels within the range of peak values in adults, suggesting that in males, gonads were physiologically mature several years in advance of the age of first breeding. One year old macaroni penguins had elevated progesterone levels and basal estradiol levels, but in 2-4 year olds plasma levels of both progesterone and estradiol were low. This does not support the hypothesis that high progesterone levels "block" ovarian maturation in immature penguins. Immature gentoo penguins showed a different pattern of hormone secretion. Plasma testosterone was low in all breeding periods, but estradiol levels increased to a peak during the incubation period, 4 weeks later than peak values occurred in adults. In both species, therefore, deferred sexual maturity was associated with delayed and/or reduced secretion of LH and gonadal steroids. PMID- 1601257 TI - Protein production and the molting cycle in the crayfish Astacus leptodactylus (Nordmann, 1842). II. Hemocyanin and protein synthesis in the midgut gland. AB - The midgut gland from the crayfish Astacus leptodactylus synthesizes and secretes hemocyanin and proteins linearly for at least 24 hr in vitro. There are no sex specific differences in the rate of protein and hemocyanin synthesis. During a standard incubation of 5 hr, up to 64% of the newly synthesized protein represents hemocyanin, which is also the predominant secretory protein. There are pronounced changes in the rate of hemocyanin synthesis during the molting cycle which coincide with corresponding changes in total protein synthesis. The titer of protein and hemocyanin synthesis during an intermolt phase exhibits a biphasic profile with the highest values in intermolt stage C4 and in premolt stage D1. PMID- 1601258 TI - Serotonin and dopamine turnover in the female rainbow trout (Oncorhynchus mykiss) brain and pituitary: changes during the annual reproductive cycle. AB - Brain serotonin (5HT) and dopamine (DA) turnover were studied at various stages of the reproductive cycle of the female rainbow trout by simultaneous determination by HPLC of neurotransmitters and major related metabolites. An increase of 5HT turnover in telencephalon and hypothalamus and a decrease of DA turnover in pituitary and hypothalamus were observed during the periovulatory period. Some changes also occurred during vitellogenesis: decreased 5HT metabolite in telencephalon and preoptic area and increased DA content in preoptic area. These data suggest that physiological fluctuations of biogenic amines could be involved in both ovarian recrudescence and ovulation, with major effects on the hypothalamo-hypophysial complex during the periovulatory period. PMID- 1601260 TI - Role of the midgut gland in metabolism and excretion of ecdysteroids by lobsters, Homarus americanus. AB - The chromatographic profile of ecdysteroids (Ecds) from the midgut gland (MG) of juvenile female lobsters, Homarus americanus, was examined using high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA) over four stages of the molt cycle. Upon initial examination, highly polar Ecd conjugates appeared to be the principal metabolites found in all molt stages. HPLC fractions containing apolar Ecds initially exhibited low RIA activity. Upon hydrolysis with a Helix pomatia enzyme preparation and reanalysis, significant amounts of other Ecds were released. Amounts of apolar Ecd conjugates were estimated, at their highest levels, to be at least 50% of the total Ecds in MGs of molt stage D3 lobsters. Only the MG formed significant amounts of apolar Ecds upon in vitro culture with [3H]ecdysone ([3H]E). Epidermis and antennal gland significantly increased their rates of [3H]E metabolism in vitro between molt stages C4 and D1. This result further supports the idea that regulation of ecdysteroid metabolism, at least in selected tissues, may be important in the molt cycle regulation of hormone titers. Using gel filtration column chromatography and sucrose density gradient centrifugation analyses, evidence was found for association of apolar Ecds with a protein(s) from MG cytosol. The protein was estimated to have a molecular weight of 180,000-200,000 and specifically bound apolar Ecds. PMID- 1601259 TI - Changes in plasma thyroxine, estradiol-17 beta, and 17 alpha,20 beta-dihydroxy-4 pregnen-3-one during smoltification of coho salmon. AB - Circulating levels of plasma estradiol, 17 alpha,20 beta-dihydroxy-4-pregnen-3 one (17 alpha,20 beta PROG), and thyroxine were measured during smoltification of coho salmon in two successive years (1984 and 1985). Two elevations of thyroxine occurred in both years, the first occurred in April followed by a second increase in May. Estradiol levels were dynamic with variable changes particularly in postsmolts when estradiol levels were either depressed in 1984 or high in 1985. However, elevations of estradiol preceded the second elevation of thyroxine in May in both years when the salmon were undergoing the later stages of smoltification. There were no consistent changes of plasma 17 alpha,20B PROG during this period. Although, in 1984, there were significant elevations and depressions of 17 alpha,20B PROG, and in 1985, there was a major unexplained depression of 17 alpha,20B PROG on April 24. There were no sexual differences noted for plasma steroid levels in the juvenile fish. These data suggest that there are seasonal changes of estradiol coinciding with other developmental changes during smoltification. PMID- 1601261 TI - N-acetylation and C-terminal proteolysis of beta-endorphin in the anterior lobe of the horse pituitary. AB - beta-Endorphin is post-translationally processed to both N-acetylated and C terminally shortened derivatives in the anterior lobe of the horse pituitary, a processing pattern qualitatively different from that of the rat and virtually every other mammalian species. Thus, separation of the molecular forms of beta endorphin using gel filtration and ion exchange chromatography showed that the horse anterior lobe primarily contains beta-endorphin-1-31 and N-acetyl-beta endorphin-1-27 along with smaller amounts of beta-lipotropin, beta-endorphin-1 27, and N-acetyl-beta-endorphin-1-31 and -1-26, in contrast to the rat anterior lobe, which contains approximately equal amounts of beta-lipotropin and beta endorphin-1-31. Immunohistochemical experiments using an antiserum which specifically recognizes N-acetylated beta-endorphin peptides confirmed that N acetyl-beta-endorphin immunoreactivity is present in the anterior lobe of the horse, but not the rat. The intermediate lobe of both species primarily synthesizes N-acetylated, C-terminally shortened beta-endorphin peptides, and while distinct species differences do occur, they were relatively minor, consisting of quantitative differences in the relative proportion of each peptide. These results are consistent with earlier reports that beta-endorphin processing in the rat pituitary is tissue specific; the anterior and intermediate lobes produce entirely different sets of beta-endorphin peptides. In the equine pituitary, however, both pituitary lobes produce the same multiple beta-endorphin forms, possessing both opioid and nonopioid properties, although their relative amounts differ. PMID- 1601262 TI - The effect of anoxic submergence and recovery on circulating levels of catecholamines and corticosterone in the turtle, Chrysemys picta. AB - The ability of some freshwater turtles to tolerate prolonged anoxia is well known. The role of hormones in the regulation of the metabolic adjustments that occur during anoxia, however, is unknown. This study examined the changes in plasma glucose, lactate, catecholamine, and corticosterone levels during submergence anoxia and recovery at 22 degrees C in the painted turtle, Chrysemys picta. Plasma catecholamine levels increased greatly during anoxia, while corticosterone levels decreased. During recovery from anoxia, plasma catecholamine levels fell rapidly while corticosterone levels increased 10-fold over controls. The results are consistent with a role for the catecholamines and corticosterone in the regulation of glucose metabolism in the turtle during anoxia and recovery, respectively. We hypothesize that the catecholamines function to stimulate hepatic glycogenolysis during anoxia and thereby increase plasma glucose levels. Corticosterone may function in the recovery from anoxia by enhancing the resynthesis of liver glycogen from lactate. PMID- 1601263 TI - Metabolic actions of glucagon and dexamethasone in liver of the ureogenic teleost Opsanus beta. AB - Injection with pharmacological doses of dexamethasone (5 mg/kg) and/or bovine glucagon (1 mg/kg) exerts pronounced effects on toadfish liver compared with vehicle-treated control fish. Affected parameters include hepatic levels of glycogen and the activities of glutamate dehydrogenase, aspartate aminotransferase, malate dehydrogenase, and enzymes involved in NADPH generation as well as the kinetics of pyruvate kinase. Activities of tyrosine aminotransferase, however, a prime target for hormonal induction in mammals, remain unchanged in Opsanus. In subsequently isolated toadfish hepatocytes, metabolite concentrations and flux through gluconeogenesis are altered as are in vitro responses to epinephrine and catfish glucagon in previously injected fish. Contrary to existing mammalian models, short-term regulation of urea cycle activity can be ruled out for toadfish, since hormone treatments fail to influence the activity of two ornithine-urea cycle enzymes or the rate of hepatocyte-urea synthesis. Treatment-dependent increases in hepatic glutamine synthetase, the unique feeder enzyme for ammonia "nitrogen" in fish urea cycle, indicate a potentially pivotal role for this enzyme in longer-term regulation of ureogenesis. PMID- 1601264 TI - Plasma and follicular tissue steroid levels in the elasmobranch fish, Torpedo marmorata. AB - Steroid concentrations in plasma and follicular tissues (theca plus granulosa layers) were determined by radioimmunoassay in the aplacental viviparous ray, Torpedo marmorata, during various stages of the reproductive cycle. Steroids in the uterine fluid of pregnant animals and in preovulatory atretic follicles were also measured. In the follicular tissue of cyclic animals, levels of progesterone were always lower than those of estradiol-17 beta and androgens (testosterone plus 5 alpha-dihydrotestosterone). Estradiol-17 beta and androgen levels increased as the animals approached the ultimate maturational stage before ovulation. Androgens were not detectable in plasma, while estradiol-17 beta increased dramatically before ovulation. In pregnant animals, only small ovarian follicles (less than 5 mm in diameter) were observed, and these had hormone concentrations that were similar to those of the small follicles of cyclic animals. Progesterone was the only steroid detected in the uterine fluid of pregnant animals. In completely sclerotic atretic follicles of pregnant animals, steroids were not detected. Progesterone was the main hormone in atretic follicles undergoing yolk resorption. This suggests that the latter may contribute to the elevated plasma progesterone concentrations of pregnant animals. PMID- 1601266 TI - Pattern of the mantle adenylate cyclase activity during the reproductive cycle of the female Mytilus galloprovincialis. AB - In the mantle of the female sea mussel Mytilus galloprovincialis seasonal variations in the adenylate cyclase activity correlate with gonadal development. Two peaks of adenylate cyclase activity were found in spring and autumn, both periods of gonadal development. The lowest enzymatic activities were in summer, a gonadal resting period. PMID- 1601265 TI - Localization and quantification of angiotensin II (A II) binding sites in the kidney of Xenopus laevis--lack of A II receptors in the adrenal tissue. AB - The distribution and properties of angiotensin binding sites in the kidney of the clawed toad Xenopus laevis were studied using quantitative in vitro autoradiography. Specific binding sites for [125I]-[Val5]-angiotensin II (A II) were located in the glomeruli of the kidney but not in the adrenal tissue. [125I] [Val5]-A II binding was equilibrated after 45 min. Scatchard and Hill analyses of saturation experiments showed that [125I]-[Val5]-A II binds to a single class of binding sites with a dissociation constant (Kd) of 1.884 +/- 0.535 nM and a maximum binding capacity (Bmax) of 0.484 +/- 0.144 fmol/mm2 (n = 8). Various angiotensin analogues displaced [125I]-[Val5]-A II in the rank order [Sar1, Ile5] A II greater than human A II greater than [125I]-[Val5]-A II = [Val5]-A II = human A III much greater than human A I. Unrelated peptides did not alter the binding of [125I]-[Val5]-A II. Acclimation to 1.5% seawater increased [125I] [Val5]-A II binding in glomeruli after 12 hr but returned to control levels after 7 days. Steroidogenic and catecholaminergic actions of [Val5]-A II on the adrenal tissue were examined in vitro and in vivo. Compared with known interrenal stimulators [human ACTH(1-39) and AVT] minimal effects were obtained only in vitro with high doses of [Val5]-A II while catecholamine release was unaffected. In vivo a single injection of 3 nmol [Val5]-A II per 100 g body wt did not change serum levels of corticosterone, aldosterone, epinephrine, norepinephrine, or dopamine. PMID- 1601267 TI - Cortisol content of eggs and larvae of teleosts. AB - The whole-animal content of the cortisol was measured in embryos and larvae of tilapia (Oreochromis mossambicus), rainbow trout (Oncorhynchus mykiss), ayu (Plecoglossus altivelis), milkfish (Chanos chanos), and yellowfin bream (Acanthropagrus latus) by radioimmunoassay following the validation of an extraction method. The total cortisol content in tilapia was 50.3 +/- 19.1 pg immediately following fertilization, then decreased abruptly and maintained a lower level of 10-17 pg until larval hatching; after hatching the cortisol content increased to 47.2 +/- 11.9 pg by the seventh day. Newly hatched rainbow trout had 60.3 +/- 6.4 pg cortisol and then increased their cortisol level slowly to 83.0 +/- 7.2 pg by the fifth day after hatching. Ayu larvae contained 5.2 pg cortisol immediately following hatching. On the other hand, pelagic milkfish revealed a much lower cortisol level, being undetectable from hatching until the second day and ranging from 0.4 to 3.7 pg from the third to seventh day after hatching. Yellowfin bream, demonstrating a similarity to milkfish, were not found to have any detectable cortisol from hatching until the third day, but presented 1.6-7.7 pg from the fifth to seventh day after hatching. The presence and clearance of cortisol during early development of fertilized eggs of tilapia suggest a maternal origin of the hormone. The amount of cortisol deposited in the larval body of tilapia increased after hatching from 25% to nearly 100% of the total cortisol in whole larvae, while that in the larval yolk sac decreased to an undetectable level, implying that the increased cortisol may be produced or secreted by the larva. The possible role of cortisol in larval development is discussed. PMID- 1601268 TI - Immunocytochemical identification of growth hormone- and prolactin-producing cells in the hypophysis of the newt Triturus cristatus carnifex Laur. AB - Single indirect immunocytochemical methods (immunofluorescence, PAP, and ABC) and double sequential staining (ABC followed by immunofluorescence) were used to localize GH- and PRL-producing cells in the pituitary distal lobe from Triturus cristatus. The following antisera were employed: rabbit anti-ovine PRL, anti-Rana catesbeiana PRL, anti-ovine GH, anti-bovine GH, and monkey anti-rat GH. A cell population corresponding to type-2 acidophils localized in the dorsal and central region, under the intermediate lobe, immunoreacted with GH antisera. Both ovine and bullfrog PRL antisera labeled a large cell population, corresponding to type 1 acidophils, predominantly localized in the ventral anterior two-thirds of the gland. The pattern of localization shown by the two cell types, although consistent with the majority of data on adult amphibians, disproves the findings obtained on the same species by other authors. PMID- 1601269 TI - In vitro uterine contractions in the viviparous lizard Tiliqua rugosa: effects of gestation and steroid pretreatment in vivo. AB - Uterine contractility was investigated in the viviparous lizard Tiliqua rugosa. Arginine vasotocin (AVT) induces rhythmic contractions in vitro in strips of uterine tissue from ovariectomized female T. rugosa. The strength of these contractions was related to the dosage of AVT and reduced by pretreatment in vivo with both progesterone and estradiol-17 beta. The frequency of spontaneous and AVT-induced contractions was enhanced by estradiol-17 beta pretreatment. The strength of AVT-induced contractions in pregnant females was not significantly different from that recorded in nonpregnant females. Spontaneous rhythmic contractions were present only in pregnant females. Ovariectomy did not affect either spontaneous or AVT-induced contractions in pregnant females. The data indicate that ovarian steroids modulate uterine contractility in T. rugosa. It is suggested that, following a decline in plasma progesterone levels, estrogen may be involved in the onset of parturition. PMID- 1601270 TI - Tetrapod-like hypothalamo-hypophysial portal system in the teleost Megalops cyprinoides (Broussonet). AB - A tetrapod-like hypothalamo-hypophysial portal system and a persistent bucco hypophysial canal are present in Megalops cyprinoides. The complicated loops of the primary capillary plexus are seen on the ventral side of the infundibular floor and contact the perikarya of the nucleus lateralis tuberis and the preoptico-hypothalamo-neurohypophysial-neurosecretory tract. Although the pars intermedia receives part of its vascular supply from the pars distalis, the caudal hypophysial artery directly vascularizes the neurointermedia interface and forms the plexus intermedialis. The bucco-hypophysial canal is short and narrow in the fry and fingerlings but becomes long and tortuous as the fish grows. Megapopidae seem to be closer to the polypteriformids than to the teleosts. The possession of the pituitary portal system in megalopids may be a connecting link between the polypteriformids and other advanced teleosts. PMID- 1601272 TI - Insulin-like immunoreactivity and molting in Rhodnius prolixus. AB - Two prominent cells were observed when fifth stage Rhodnius female larval brains were stained with anti-insulin serum. The staining intensity of these cells varied during the instar, being lowest on Day 1 and Days 5 and 6 after feeding. Injection of anti-insulin serum into 5th stage larvae immediately after feeding and on Days 4 and 5 in females and on Days 5 and 6 in males prevented molting. Control antiserum had no effect on the molting process. Injections at other times during the instar had no effect unless serum was injected just prior to ecdysis. Control or anti-insulin serum injected at this time disrupted normal ecdysis. These results are discussed in terms of the control of the developmental program of the insect. PMID- 1601271 TI - Identification of an androgen receptor in the zonal testis of the salamander (Necturus maculosus). AB - The testis of the salamander, Necturus maculosus, is advantageous for studying biochemical changes during spermatogenesis because germ cells and associated Sertoli and Leydig cells are topographically separated by stage of development. Using extracts of staged tissue samples and [3H]testosterone (T) in a standard binding assay, followed by Sephadex LH-20 or DNA-cellulose chromatography to separate free and bound steroid, we have identified a T-binding protein having physicochemical characteristics of a classical androgen receptor (AR): high affinity (Kd = 10(-9) M), limited capacity (Bmax) = 10(-10) M or 350 fmol/g tissue) and androgen specificity (T = 5 alpha - dihydrotestosterone greater than progesterone = corticosterone greater than estradiol). AR was present in nuclear extracts, where greater than 80% of binding sites were occupied by endogenous ligand, but was not detectable in cytosol. On linear sucrose gradients, nuclear AR sedimented at 3-4 S in both low and high ionic-strength buffers and, by this and other criteria, was distinguishable from the nonreceptor androgen binding protein (ABP) of the same species. The diffuse distribution of AR in germinal and nongerminal (glandular) tissues at all developmental stages is consistent with a dual localization in Sertoli cells and Leydig cells, as previously reported in mammals, and further suggests a regulatory role of androgen throughout spermatogenesis. PMID- 1601273 TI - Seasonal variations in the daily rhythm of pineal gland and/or circulating melatonin and 5-methoxytryptophol concentrations in the European hamster, Cricetus cricetus. AB - Day-night variations in pineal and/or circulating melatonin and 5 methoxytryptophol (5-ML) concentrations were measured monthly throughout the year in female European hamsters, Cricetus cricetus, maintained under natural conditions. Pronounced seasonal variations in the day-night rhythm of both melatonin and 5-ML were observed. As previously reported for melatonin, the daily rhythm of both methoxyindoles disappeared in spring and early summer, while a clear day-night rhythm occurred in autumn, winter, and early spring. The amplitude of the day-night variations appeared to be maximum from October until January. An inverse relationship existed between the rhythms of melatonin and 5 ML. PMID- 1601274 TI - Metabolism of androstenedione and 11-ketotestosterone in the kidney of the three spined stickleback, Gasterosteus aculeatus. AB - Stickleback kidneys were incubated with tritiated androstenedione (A4) or 11 ketotestosterone (OT). After the A4 incubations the following steroids were found, testosterone (T), 5 beta-androstane-3,17-dione (5 beta Ad), etiocholanolone (Et), 5 beta-dihydrotestosterone (5 beta DHT), 5 beta-androstane 3 alpha,17 beta-diol (5 beta A3 alpha 17 beta diol), androsterone, 5 alpha androstane-3,17-dione, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha A3 alpha 17 beta diol), as well as glucuronides of T, Et, 5 beta DHT, 5 beta A3 alpha 17 beta diol, and 5 alpha A3 alpha 17 beta diol. The metabolites found in the largest amounts were usually T, 5 beta Ad, Et, and the glucuronides of T, Et, and especially of 5 beta A3 alpha 17 beta diol. These results suggest the main pathway to be A4-5 beta Ad-Et-5 beta A3 alpha 17 beta diol-5 beta A3 alpha 17 beta diol-glucuronide or Et-Et-glucuronide-5 beta A3 alpha 17 beta diol glucuronide. The formation of 5 beta-reduced compounds was larger in postbreeding males and females than in breeding males. The opposite was the case for 5 alpha reduced compounds. The total formation of glucuronides was lower in the breeding males than in the other groups. After the OT incubations 11-ketoandrostenedione, 17 beta-hydroxy-5 beta-androstane-3,11-dione (tentatively identified), and OT glucuronide were found. 17 beta-Hydroxy-5 alpha-androstane-3,11-dione was not present. PMID- 1601275 TI - Structure and expression of bombyxin-related peptide genes of the moth Samia cynthia ricini. AB - From the genomic DNA of the moth Samia cynthia ricini, we cloned and characterized six clustered genes that encode precursor molecules for peptides structurally related to bombyxin, a Bombyx mori brain secretory peptide that is structurally like insulin and functionally like the prothoracicotropic hormone. The precursor molecules deduced from these genes have the domain organization of signal peptide/B-chain/C-peptide/A-chain, as in preprobombyxins and preproinsulins. The Samia bombyxin-related peptide (SBRP) genes are classified into families A and B according to their sequence homology. Two genes belonging to different families are arranged close to each other to form a pair with opposite transcriptional orientations (A-1/B-1, A-2/B-2, and A-3/B-3). None of these genes have introns, and gene B-3 has an in-frame stop codon representing a pseudogene. Four genes, A-1, A-3, B-1, and B-2, are expressed in Samia brain. Genomic Southern hybridization suggests that the Samia genome contains many other SBRP genes. PMID- 1601276 TI - Calcitonin of the stingray: comparison of the hypocalcemic activity with other calcitonins. AB - Hypocalcemic potency of calcitonin isolated from the stingray (cartilaginous fish), Dasyatis akajei, was examined using the rat bioassay and compared with the activities of other calcitonins (human, pig, salmon, eel, and fowl). The potency of Dasyatis calcitonin (dCT) was estimated to be 1500-3800 IU/mg. However, when the duration of the hypocalcemic effect of dCT was taken into consideration, it was judged that dCT was approximately 2.4-6.2 times more potent than mammalian calcitonins, but about 2.3-3.5 times less active than other nonmammalian calcitonins. PMID- 1601277 TI - Impact of complete isletectomy on plasma glucose in the southern hemisphere lamprey Geotria australis. AB - The adult southern hemisphere lamprey Geotria australis is the only known vertebrate in which it is possible to remove all of the pancreatic islet tissue without damaging other organs. In the 24 hr after isletectomy, the plasma glucose of adult G. australis rose sharply from 5.0 to 11.6 mmol.liter-1 and remained at a similar elevated level throughout the subsequent 5 days of the experiment. The marked hyperglycemia that follows complete isletectomy parallels the results obtained after removal of the majority of the islet tissue from northern hemisphere lampreys and after pancreatectomy in mammals, but contrasts with observations recorded for some other groups of vertebrates. PMID- 1601278 TI - Seasonal variations of androgens and of several sexual parameters in male Meriones shawi in southern Morocco. AB - Seasonal changes of several parameters related to sexual activity were studied in the gerbil (Rodentia: Gerbillidae). The weight of the testes, seminal vesicles, and adrenals fluctuate throughout the year. Plasma androgen levels and histological aspect of the testes also vary throughout the year. Spermatogonial and steroid activities are synchronous and are maximal in winter and spring. The relationship between these activities and environmental climatic parameters is discussed: the beginning of sexual activity seems correlated with the first rains. PMID- 1601279 TI - Regulation of methyl farnesoate in the hemolymph and mandibular organ of the lobster, Homarus americanus. AB - Methyl farnesoate (MF) was measured in the hemolymph and mandibular organs (MO) of the lobster. Although a few animals had detectable MF levels in their hemolymph, this compound was undetectable (less than 0.4 ng/ml) in the hemolymph of most animals. One day after bilateral eyestalk ablation, MF was detected in the hemolymph of all animals, reaching variable levels (2.0-31.2 ng/ml) by the fourth day. Unilateral eyestalk ablation caused a smaller increase in hemolymph levels of MF. Similarly, the MF content of the MO, the only known site of MF synthesis, was low in intact lobsters (8.1 ng/gland) and was elevated in unilaterally and bilaterally eyestalk-ablated animals (54.1 and 106.9 ng/gland, respectively). When extracts of the sinus gland (SG), a source of neuropeptides in the eyestalk, were injected into bilaterally ablated lobsters, hemolymph levels of MF dropped to undetectable levels in 2 to 3 hr. The response to SG extract was dose dependent, and MF levels recovered by 12 to 24 hr after treatment. SG extract also lowered the MF content in the MO from 267.6 to 6.6 ng/gland after 4 hr. These results indicate that MF in the hemolymph and MO is negatively regulated by a factor(s) from the SG. PMID- 1601280 TI - A nonsteroidal follicular factor is involved in maturation process of Xenopus laevis oocytes. AB - Xenopus laevis postvitellogenic ovarian follicles release into conditioned medium nonsteroidal factor(s) that potentiate progesterone-induced oocyte maturation. The molecular weight of this factor is between 1000 and 10,000 Da. The potentiating activity is suppressed when follicles are incubated with cyanoketone to inhibit steroidogenesis, suggesting that the secretion of the potentiating factor can be modulated in vitro. These results indicate that the steroid independent pathway in vitro, previously reported in oocytes exposed to insulin or IGF-1 to induce meiotic resumption, may be of physiological importance. PMID- 1601281 TI - Properties of T4 5'-deiodinating systems in various tissues of the rainbow trout, Oncorhynchus mykiss. AB - L-Thyroxine (T4) 5'-monodeiodinase (5'D) activity was examined in the microsomal fractions of liver, kidney, gill, white skeletal muscle, and red blood cells (RBC) of fed rainbow trout held in freshwater at 12 degrees. Two distinct 5'D systems were established and were examined at low (0.08-1.3 nM) or high (1.6-25 nM) T4 substrate ranges. The low substrate 5'D occurred in liver, gill, and muscle, but not in kidney or RBC. The pH optimum was 7.0 and the optimum dithiothreitol (DTT) level ranged from 7 to 10 mM. The Km values (nM) were liver, 0.098; muscle, 0.198; and gill, 0.168. The Vmax values (pmol.hr-1.mg protein-1) were liver, 3.74; muscle, 0.79; and gill, 0.62. DTT affected both the Vmax and the Km, and propylthiouracil (PTU) inhibited the Vmax. These data suggest a ping pong type mechanism. In contrast, the high substrate 5'D occurred only in liver (pH 7 optimum, DTT optimum 15 mM) and in kidney (pH optima 6 and 8, DTT optimum 15 mM). The Km values (nM) were liver, 10.0; and kidney, 14.7; the Vmax values (pmol.hr-1.mg protein-1) were liver, 8.21; and kidney, 5.76. DTT affected the Vmax but not the Km and PTU did not inhibit, indicating a sequential type mechanism. In conclusion, in rainbow trout there are at least two types of 5'D which differ in their tissue distribution, T4 substrate affinity, and enzyme mechanism, and which do not resemble in their combined properties the 5'D forms established in higher vertebrate taxa. PMID- 1601282 TI - Seasonal and lactational effects on the prolactin response to a dopamine antagonist and TRH in the Bennett's wallaby (Macropus rufogriseus rufogriseus). AB - In the Bennett's wallaby prolactin is thought to maintain lactational and seasonal quiescence and is essential for early lactation. However, plasma prolactin concentrations determined in daily or weekly samples at these times are unchanged. In the present study, female Bennett's wallabies were blood sampled at 2-hr intervals over a 24-hr period during seasonal quiescence on either natural or artificial photoperiods to determine whether a diurnal rise of prolactin occurs at this time. Prolactin concentrations did not exhibit a diurnal change. Further experiments were aimed at determining whether there was an increase in the prolactin response to a dopamine antagonist or TRH during the transition to seasonal quiescence. Nonlactating and lactating female Bennett's wallabies were treated with saline, 0.5, 1, and 2 mg of the dopamine antagonist domperidone and 100 micrograms TRH in October, December, February, and April. In both groups there was a significant elevation in plasma prolactin concentration in response to domperidone with an increasing response at each successive month. In early (October and December) and peak (April) lactation the prolactin response was greater in lactating animals. There was no significant prolactin response to TRH in lactating animals. In nonlactating wallabies, the prolactin response to TRH was increased in February. At peak lactation (April), the response to 1 mg domperidone was blocked when the dose was administered 2 hr after temporary removal of pouch young (RPY). With either larger doses (20 mg) or a 1-mg dose injected 8 hr after RPY, a significant prolactin response was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601283 TI - Mapping of the PCK1 gene encoding phosphoenolpyruvate carboxykinase on chromosome XI of Saccharomyces cerevisiae. AB - The gene PCK1 encoding phosphoenolpyruvate carboxykinase of Saccharomyces cerevisiae has been mapped on the right arm of chromosome XI, 12.7 centimorgans proximal to MAL4 and 20.1 centimorgans distal to MET1. In order to map the gene, hybridization of PCK1 DNA with separated yeast chromosomes and tetrad analysis of diploids with adequate markers were carried out. PMID- 1601284 TI - Duplication of a DNA sequence homologous to genes for immunoglobulin receptors and M proteins in Streptococcus pyogenes. AB - The nucleotide sequence of an open reading frame of 355 amino acids downstream of the IgA-binding protein gene arp4 in Streptococcus pyogenes M-type 4 has been determined. Analysis of the deduced amino acid sequence for the open reading frame shows an extensive homology to streptococcal M proteins and immunoglobulin binding proteins. Expression of the open reading frame has not been detected and the function may be as a genetic reservoir in the generation of new immunoglobulin receptors and antigenic variants of M proteins. PMID- 1601285 TI - Characterization of the promoter region of the basidiomycete Lentinus edodes Le.ras gene. AB - An analysis of the 2.7-kb nucleotide sequence including the 5'-flanking region of the basidiomycete Lentinus edodes Le.ras-encoding gene revealed that the promoter region contains a CAAT box, a CACCC box, two consecutive TATAAA boxes, and a CT rich sequence element, in that order, from upstream to downstream. One major and two alternative transcriptional initiation sites are located 132 nucleotides and 85 and 90 nucleotides downstream from the downstream TATAAA box, and the major site is positioned just in the CT-rich sequence. PMID- 1601286 TI - Comparison of Vibrio parahaemolyticus hemolysin (Vp-TRH) produced by environmental and clinical isolates. AB - TDH-related hemolysin (Vp-TRH) produced by Kanagawa-phenomenon-negative (KP-) Vibrio parahaemolyticus has been demonstrated to be a possible virulence determinant. Though almost half of KP- isolates examined from diarrhoeal patients produced Vp-TRH, few reports mentioned the ability of environmental isolates to produce Vp-TRH. Considering the route of infection with V. parahaemolyticus, this toxin must be produced by the organisms in the sea or in sea food. To confirm that Vp-TRH produced by V. parahaemolyticus could be involved in sea-food-borne diarrhoeas, Vp-TRH-producing strains were isolated from the environment, identified and hemolysin purified from these strains was compared to hemolysin (Vp-TRH) isolated from diarrhoeal patients. The results showed that the hemolytic activity, antigenicity, reactivity in the rabbit ileal loop test and N-terminal amino acid sequence of Vp-TRH from environmental strains was indistinguishable from the toxin of clinical origin. PMID- 1601287 TI - Nucleotide sequence of a genomic and a cDNA clone encoding an extracellular alkaline protease of Aspergillus fumigatus. AB - An Aspergillus fumigatus extracellular alkaline protease (ALP) which is an enzyme of the subtilisin family is a potential virulent factor of the fungus. The gene encoding ALP was isolated from a genomic library made from DNA of an A. fumigatus isolate. The nucleotide sequence of this gene was compared to that of a cDNA encoding A. oryzae ALP and to that of a cDNA from A. fumigatus encoding the mature ALP protein. Mature A. fumigatus ALP contains 282 amino acids and is encoded by three exons. The pre-proenzyme has a leader sequence of 121 amino acids. PMID- 1601288 TI - Identification of putative multifunctional peptide synthetase genes using highly conserved oligonucleotide sequences derived from known synthetases. AB - Many peptide antibiotics in prokaryotes and lower eukaryotes are produced non ribosomally by multi-enzyme complexes. Analysis of gene-derived amino acid sequences of some peptide synthetases of bacterial and fungal origins revealed a high degree of conservation (35-50% identity). The genes encoding those peptide synthetases are clustered into large operons with repetitive domains (about 600 amino acids), in the case of synthetases activating more than one amino acid. We used two 35-mer oligonucleotides derived from two highly conserved regions of known peptide synthetases to identify the surfactin synthetase operon in Bacillus subtilis ATCC 21332, a strain not accessible to genetic manipulation. We show that the derived oligonucleotides can be used not only for the identification of unknown peptide synthetase genes by hybridization experiments but also in sequencing reactions as primers to identify internal domain sequences. Using this method, a 25.8-kb chromosomal DNA fragment bearing a part of the surfactin biosynthesis operon was cloned and partial sequences of two internal domains were obtained. PMID- 1601289 TI - Endoglucanase A from Cellulomonas fimi in which the hinge sequence of human IgA1 is substituted for the linker connecting its two domains is hydrolyzed by IgA proteases from Neisseria gonorrhoeae. AB - The hinge in IgA1 and the linker in endoglucanase A (CenA) are quite similar. The IgA1 hinge is 18 amino acids long and contains only proline, threonine and serine. The linker in CenA is 27 amino acids long and contains only proline, threonine and a single serine. IgA proteases from Neisseria gonorrhoeae cleave Pro-Ser and Pro-Thr bonds within the IgA1 hinge sequence, but they do not attack CenA. When the linker sequence of CenA is replaced with the hinge sequence of IgA1, the hybrid polypeptide is susceptible to the N. gonorrhoeae proteases. It is cleaved within the hinge sequence at the same sites as IgA1. PMID- 1601290 TI - Medicare's PPS implementation and increase in recording of psychotic depressive disorder: some thoughts on the reasons. PMID- 1601291 TI - Changes in diagnostic case mix in psychiatric care in general hospitals, 1980-85. AB - The Hospital Discharge Survey of 1980 and 1985 was used to assess changes in diagnostic case mix of psychiatric inpatient care in short-term, nonfederal general hospitals. Information regarding presence of psychiatric and chemical dependency units was added to both surveys, and information regarding exemption from Medicare's PPS system was noted for 1985. The largest increase was in ICD-9 code 296 (affective disorder), which more than doubled in frequency, along with a similar decrease in Diagnosis-Related Group 426, depressive neurosis. One explanation for this sizable shift was "gaming the system." One cannot conclusively, however, distinguish between gaming the system and the effects of changing professional views of depression during this time period. Other variables potentially contributing to the effect are described as well. PMID- 1601292 TI - Migraine visual auras. A medical update for the psychiatrist. AB - Auras of visual aberrations as well as other neurological disturbances including somatosensory and perceptual symptoms that precede a headache distinguish migraine with aura (classic migraine) from migraine without an aura (common migraine) and other varieties of headache. Visual auras that characterize migraine with aura can be classified and distinguished from other neurologic and psychiatric causes of visual aberrations. Examples of migraine visual auras, which are often described but rarely shown in the medical literature, are presented and their mechanism is discussed. PMID- 1601293 TI - Chronic mental illness and perinatal outcome. AB - A retrospective review of pregnant women admitted to a state psychiatric facility and to an acute university psychiatric unit compares various characteristics of the two populations. No major significant differences were noted in demographic, psychiatric, or obstetric characteristics. It was hypothesized that the patients from the state facility would have a better perinatal outcome secondary to an opportunity for closer prenatal follow-up. No differences were noted in perinatal outcomes between the two facilities. Significantly poorer perinatal outcomes were noted in the combined group of psychiatric patients when compared were noted in the combined group of psychiatric patients when compared with the state of Oregon's birth-outcome statistics. The importance of prenatal care in this high risk population is discussed, and specific recommendations are offered. PMID- 1601294 TI - Consultation-liaison psychiatry in Brazil. Psychiatric residency training. AB - A mailing survey assessed consultation-liaison (C-L) service delivery and training among all 23 approved psychiatric residency training programs throughout the country. Twenty questionnaires were returned. Outpatient, inpatient, emergency, and consultation services were present together in 35% of the academic hospitals where residency training took place. Consultation service was provided by 18 (90%) responding programs. Eleven of those reported C-L training as part of their general psychiatry rotation. Nevertheless, educational objectives, weekly case conferences, and didactic seminars were provided by only five of them. The training time varied from 40 to 560 hours, 190 hours on average. The same five programs offered an elective third-year residency training, including liaison with specific units. The results illustrate the migration of academic psychiatric departments from the psychiatric hospital to the general hospital as well as the beginning of C-L training programs in Brazil. PMID- 1601295 TI - Extrapyramidal side effects of antiemetics presenting as psychiatric illness. AB - Although extrapyramidal side effects of two commonly used antiemetics, metoclopramide and prochlorperazine, are well known, it may be difficult for even the experienced practitioner to distinguish some of these extrapyramidal reactions from such psychiatric symptoms as anxiety, depression, or catatonia. Certain patient groups have increased susceptibility to these extrapyramidal reactions, including patients under 30, those with AIDS, those with renal disease, oncology patients, and possibly women. Physicians should maintain a high index of suspicion for depression, anxiety, or catatonia if their patients are taking antiemetics. These symptoms may be extrapyramidal side effects of the antiemetic rather than indications of a primary mental disorder. PMID- 1601296 TI - Psychiatric morbidity in a general medical ward. Hong Kong's experience. AB - The psychiatric morbidity of a general hospital's male medical ward in Hong Kong was studied using a one-stage single-rater method. Medical diagnoses were made according to ICD-9 on 91.5% of patients and 24% were diagnosed with DSM-III. The most common mental disorders included substance use disorder, dementia, and delirium. Of all the patients, 8.5% were not medically diagnosable and 5.3% were given only psychiatric diagnoses, the majority of which were substance use disorders. PMID- 1601297 TI - Electrocardiographic evidence of myocardial injury in psychiatrically hospitalized cocaine abusers. AB - The electrocardiograms (ECG) of 99 cocaine-abusing patients were compared with the ECGs of 50 schizophrenic controls. Eleven of the cocaine abusers and none of the controls had ECG evidence of significant myocardial injury defined as myocardial infarction, ischemia, and bundle branch block. PMID- 1601298 TI - The woman who wanted electroconvulsive therapy and do-not-resuscitate status. Questions of competence on a medical-psychiatry unit. AB - A case involving an elderly woman suffering concurrently from serious psychiatric and medical illnesses is presented. Ethical considerations concerning her treatment on a medical-psychiatry unit are discussed with special attention to her requests for both electroconvulsive therapy (ECT) and do-not-resuscitate (DNR) status. The compatibility of simultaneous requests for ECT and DNR is examined on three levels. The effect of depression upon competence to request and refuse treatment is analyzed. This case illustrates a conflict between medical and psychiatric treatment goals and ethical traditions which will become more common as psychiatrists treat older and more medically ill patients. PMID- 1601299 TI - Secondary seizures from water intoxication in anorexia nervosa. PMID- 1601300 TI - Physical and genetic mapping of cloned ribosomal DNA from Toxoplasma gondii: primary and secondary structure of the 5S gene. AB - The ribosomal DNA (rDNA encoding rRNA) of the obligately intracellular protozoan parasite, Toxoplasma gondii, was identified, cloned, physically mapped, its copy number determined, and the 5S gene sequenced. Using total RNA as a probe, a collection of recombinant lambda phages containing copies of rDNA were isolated from a lambda 2001 tachyzoite genomic library. Northern gel hybridization confirmed specific homology of the 7.5-kb rDNA unit, subcloned into pTZ18R, to T. gondii rRNA. The mapped rDNA found in pTOX1 contained small ribosomal subunit (SS; 18S)- and large ribosomal subunit (LS; 26S)-encoding genes localized using intragenic heterologous probes from the conserved sequences of the SS (18S) and LS (28S) Xenopus laevis genes. the physical mapping data, together with partial digestion experiments and Southern gel hybridization, confirmed a 7.5-kb rDNA unit arranged in a simple head-to-tail fashion that is tandemly repeated. We estimated the rDNA repeat copy number in T. gondii to be 110 copies per haploid tachyzoite genome. Parts of the SS gene and the complete 5S gene were sequenced. The 5S gene was found to be within the rDNA locus, a rare occurrence found only in some fungi and protozoa. Secondary-structure analysis revealed an organization remarkably similar to the 5S RNA of eukaryotes. PMID- 1601301 TI - Isolation and sequence of a developmentally regulated putative novel gene, priA, from the basidiomycete Lentinus edodes. AB - Screening for gene(s) homologous to v-Ha-ras (Harvey rat sarcoma viral ras gene) in the basidiomycete, Lentinus edodes, resulted in the isolation of a novel gene (designated priA), in addition to a ras gene homologue [Hori et al., Gene 105 (1991) 91-96]. The priA gene has a coding capacity of 258 amino acids (aa) interrupted by two short putative introns. The 5'-upstream region of priA contains GGGCGG box, CCAAT box, TATAAA box and CT sequence elements in 5'----3' order. One transcription start point (tsp) was located 10 nucleotides upstream from a TATAAA box and another tsp just in a CT sequence. The deduced PRIA protein (26.7 kDa), rich in Ser (42 residues), Pro (29 residues) and Thr (27 residues), contained different types of putative zinc-binding motifs. It initiated with a hydrophobic aa sequence and terminated with the unique sequence, Cys-Aaa-Aaa-Xaa (where Aaa is aliphatic aa and Xaa is any aa), implying an association with the inner membrane surface via acylation of the Cys residue. The priA gene expression was found to be developmentally regulated with primordia/immature fruiting bodies having much higher levels of priA transcript. Preprimordial mycelia and mature fruiting bodies, however, contain very low levels of priA transcript. The priA gene may play a role during the beginning of fruiting. PMID- 1601302 TI - The rough (ro+) gene as a dominant P-element marker in germ line transformation of Drosophila melanogaster. AB - We describe a new vector for the P-element-mediated introduction of gene constructs into the germ line of Drosophila melanogaster. The P-element vector carries 6.8 kb of genomic DNA containing the rough gene (ro) from D. melanogaster and a polylinker (MCS) containing ten unique cloning sites. To demonstrate its utility, we have cloned into the MCS of this vector, the firefly luciferase (Luc) encoding gene (luc) under the control of the D. melanogaster hsp70 promoter and have transformed flies with the resultant P-element. Single insertions of this element, whether in the hemizygous or homozygous condition, completely rescued the ro- mutation and directed heat-inducible synthesis of Luc mRNA and enzyme. PMID- 1601303 TI - Methylation of CpG-island-containing genes in human sperm, fetal and adult tissues. AB - The methylation of three human genes containing CpG islands and a CpG-depleted gene were measured in sperm, fetal and adult tissues. The c-Ha-ras was methylated extensively in the 3' region in sperm with a methylation-free region extending from the promoter to the third exon. The extent of methylation in the 3' region decreased in fetal cells, however, de novo methylation of sites closer to the island and within exon 1 were apparent. These sites were more completely methylated in adult lymphocytes and kidney. Essentially similar results were obtained with the CpG-island-containing genes, c-myc and HPRT (encoding hypoxanthine phosphoribosyl transferase), which showed that unmethylated sites near the CpG islands in sperm became methylated in fetal and adult cells. The variations in methylation seen in the non-island regions of the c-Ha-ras gene were mirrored in the insulin-encoding gene which does not contain a CpG island. The results show similar variations in methylation of non-island regions of DNA which occur independent of expression, and show that regions of extensive methylation in sperm may move closer to CpG islands in fetal and adult somatic cells. PMID- 1601304 TI - Infectious in vitro transcripts from amplified cDNAs of the Y and Kin strains of cucumber mosaic virus. AB - Using a method based on the polymerase chain reaction (PCR) with primers that include the phi 10 promoter of bacteriophage T7, we obtained cDNA clones of the three RNA genomes of two different strains of cucumber mosaic virus (CMV; Kin and Y strains) from which infectious in vitro transcripts were generated, and demonstrated that the same primers could be used for amplification of at least two other strains of CMV (O and Py). This method is rapid and requires only limited nucleotide (nt) sequence data (16-18 nt) from the termini of the RNA species. Either viral RNA or unpurified RNA samples from infected plants can be used as template for first-strand cDNA synthesis. For cDNAs of RNA1 and RNA2 of the Y strain, the transcription efficiency was substantially lower than with the Kin strain, unless the primer sequence included transcribed G residues on the 5' side of the viral cDNA, so that the promoter for T7 RNA polymerase resembled more closely the canonical sequence from the bacteriophage T7 phi 10 promoter. The lower specific infectivity of transcripts of the modified cDNAs was more than compensated for by increased transcription efficiency. The possibility that the PCR process may introduce deleterious mutations into the viral cDNA was investigated by re-amplification of a functional cloned cDNA of RNA2: all six cDNA clones of the re-amplified cDNA produced transcripts as infectious as those from the progenitor cDNA. PMID- 1601305 TI - A vector for the removal of deletion mutants from antibody libraries. AB - To reduce the number of deletion mutants from antibody (Ab) libraries that had been amplified by PCR from peripheral blood lymphocytes, we constructed the Ab expression vector, pLAB, in which DNA coding for a single-chain Ab was inserted into the gene encoding beta-lactamase (Bla) at the 3'-terminus of its signal sequence. After transforming Escherichia coli with this vector, a fusion protein with a functional Bla domain was produced that was able to protect the bacteria from the action of ampicillin (Ap). Libraries can therefore be usefully propagated with this vector, since only those clones carrying inserts that are in frame with Bla will survive Ap selection, while others that carry out-of-frame deletions or internal stop codons are eliminated. PMID- 1601306 TI - A selectable bifunctional beta-galactosidase::phleomycin-resistance fusion protein as a potential marker for eukaryotic cells. AB - The Sh ble gene, conferring phleomycin resistance (PhR), was fused in frame to both the 3' and 5' ends of the Escherichia coli lacZ gene. The bifunctionality of the resulting 130-kDa hybrid proteins was demonstrated in E. coli and in the fungus, Tolypocladium geodes. PhR transformants of both organisms could be selected for. All transformants from E. coli and most from T. geodes displayed beta Gal activity. In the fungal host, higher transformation frequencies and greater levels of beta Gal activity were observed in clones harboring the lacZ::Sh ble fusion, as compared to the Sh ble::lacZ configuration. This system appears to be a potentially useful tool for the direct selection of transformants, and the evaluation of gene expression and regulation in a wide variety of prokaryotic and eukaryotic hosts. PMID- 1601307 TI - Structural organization of the gene encoding rat cystatin beta. AB - A genomic DNA clone encompassing the gene (cy beta) encoding rat cystatin beta (Cy beta) was isolated by screening with a rat cy beta cDNA as a probe. The gene spans about 2.6 kb and comprises three exons. The first intron is located between Lys22 and Val23 and the second between Lys56 and Val57 in the deduced amino acid sequence of Cy beta. The second exon contains the highly conserved QVVAG sequence which, unlike the sequence of other cystatin family members, is not split by an intron. In the 5'-upstream region, three SP-1-binding sites exist, but no typical TATA-box or CAAT-box sequences are found. The difference in the organization of the rat cy beta gene, encoding a family-1 cystatin, from that encoding members of the other cystatin families, suggests that cy beta diverged from a common ancestral gene earlier than the separation of genes encoding family-2 and family 3 cystatins. PMID- 1601308 TI - The rat peptidylarginine deiminase-encoding gene: structural analysis and the 5' flanking sequence. AB - Genomic clones of the rat peptidylarginine deiminase (PAD)-encoding gene (PAD) were isolated, and the gene organization was analyzed by restriction mapping and nucleotide sequencing. The PAD spans more than 50 kb and contains 16 exons and 15 introns. The lengths of the introns from 0.5 kb to more than 16.5 kb. A 1.7-kb sequence in the 5'-flanking region was determined. S1 nuclease mapping revealed two putative cap sites 79 and 81 bp upstream from the N-terminal ATG codon of PAD, which had been determined by amino acid sequence analysis. This ATG was confirmed to be the translation start site, since no other ATG codon was found in the open reading frame downstream from the cap sites. The 5'-flanking sequence contains four potential SP1-binding sites, a putative Pit-1/GHF-1-binding site, four short sequences either identical or homologous to the sequences in the promoter regions of rat or human growth hormone encoding genes, as well as a sequence similar to an estrogen-responsive element. However, neither a typical TATAA box, nor CCAAT box is present. These results provide important clues for elucidating the mechanism of female-specific and/or sex cycle-dependent gene expression. PMID- 1601309 TI - Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction. AB - A human interleukin 4 (hIL-4)-encoding cDNA (hIL4) probe was used to screen a bovine genomic library, and three clones containing sequences with homology to the human and mouse IL4 cDNAs were isolated. Sequence information obtained from one of these genomic clones was used to design an oligodeoxyribonucleotide primer corresponding to the transcription start point region for use in the polymerase chain reaction (PCR). The PCR-RACE protocol, designed for the rapid amplification of cDNA ends, was successfully used to generate a full-length bovine IL4 (bIL4) cDNA clone from polyadenylated RNA isolated from concanavalin A-stimulated bovine lymph node cells. The bIL4 cDNA is 570 bp in length and contains an open reading frame of 405 nucleotides (nt), coding for a 15.1-kDa precursor of 135 amino acids (aa), which should be reduced to 12.6 kDa for unglycosylated bIL4 after cleavage of a putative hydrophobic leader sequence of 24 aa. The aa sequence contains one possible Asn-linked glycosylation site. Bovine IL4 is shorter than mouse (mIL4) and hIL4, because of a 51-nt deletion in the coding region. Comparison of the overall nt and deduced aa sequences shows a greater homology of bIL4 with hIL4 than with mIL4. This homology is not evenly distributed, however, with the nt sequences 5' and 3' of the coding region showing a much greater homology between all three species than the coding sequence. PMID- 1601311 TI - Sequence of a cDNA encoding chicken high-mobility-group protein-2. AB - There are several members of the high-mobility-group (HMG) of DNA-binding proteins, including HMG-1, HMG-2, HMG-14 and HMG-17 [Johns: The HMG Chromosomal Proteins. Academic Press, London, 1982]. We report here sequences encoding the chicken HMG-2 protein of 207 amino acids (aa). This assignment is made on the basis of available data which indicate 89% homology of the chicken aa sequence to porcine HMG-2. This compares with 78-81% homology to the HMG-1 proteins of rat, hamster, human, porcine, and bovine origin. PMID- 1601310 TI - Overproduction and large-scale purification of the human poly(ADP-ribose) polymerase using a baculovirus expression system. AB - We have overproduced the full-length human poly(ADP-ribose) polymerase (PARP) in Spodoptera frugiperda (Sf9) cells using a baculovirus expression vector system. Approx. 20 mg of purified protein from 5 x 10(8) Sf9 cells were obtained by a simple three-step purification procedure including 3-aminobenzamide affinity chromatography. The recombinant protein (rePARP), which migrates as a unique 116 kDa band on SDS-polyacrylamide gels, was identified as PARP by Western blotting using either polyclonal or monoclonal antibodies raised against the purified human and calf thymus enzymes. Furthermore, rePARP is a functional protein, as demonstrated by its ability to specifically bind Zn2+ and DNA, and to recognize single-strand breaks in DNA. The purified enzyme has the same affinity for NAD+ and turnover number as the human placental PARP. Thus, rePARP produced in insect cells is biologically active and suitable for functional analysis. The reproducibility of the overproduction and the simplicity of the purification protocol, as well as the yield of the produced protein, should greatly facilitate physicochemical and structural studies. PMID- 1601312 TI - Cloning and sequencing of the cDNA encoding a mouse tissue inhibitor of metalloproteinase-2. AB - A mouse cDNA encoding a tissue inhibitor of metalloproteinases (mTIMP-2) was cloned and the 1695-bp sequence was determined. While high homology was observed with the sequences encoding the human (hTIMP-2) and bovine (bTIMP-2) genes, mTIMP 2 contained a long 3'-nontranslated region not observed in the hTIMP-2 or bTIMP-2 genes. PMID- 1601313 TI - [Course of pregnancy in patients with known infertility]. AB - Two hundred and ninety cases of pregnant patients with antecedents of sterility, were analyzed; 55.8% corresponded to primary sterility and 44.2% to secondary sterility. About cases 38.2% corresponded to endocrine-ovarian factor; 17.9% to tuboperitoneal; 7.4% to cervico-spermatic and 36.5% of undetermined cause. The main complications of pregnancy were: abortion, ectopic pregnancy, twin pregnancy, toxemia, pre-term delivery, placenta previa, and premature detachment of normoinserted placenta. The frequency of such complications, as well as the indexes of perinatal mortality and congenital malformations, were no higher than for general population. However, analyzing separetely the different groups, it was found a notable increase the abortion and twin pregnancy indexes in factor endocrine-ovarian (25.2% and 4.5%). In tuboperitoneal the ectopic pregnancy index was higher (7.5%), and one case of heterotopic pregnancy was found. The global index for cesarean section was 47.2%, increased due to frequent use of elective section (11.2%). It is concluded that currently and because the use of diagnostic technology and surveillance since early phases, the evolution and outcome of pregnancies in women previously sterile are similar to the ones for general population. PMID- 1601314 TI - [Heterotopic pregnancy in intrauterine insemination. Presentation of a case]. AB - The heterotopic (ectopic and orthotopic simultaneous) pregnancy shows a frequency of 1 to 15,000 to 1 to 30,000 gestations. The clinical diagnosis is difficult due to the lack of precise indicators, as to diagnose an intrauterine pregnancy eliminates the possibility of ectopic pregnancy. The methods of Assisted Reproduction seem to be factors that have influenced on the increment of this type of gestations. A case of a 32 year patient with primary sterility by pelvic adhesions process, that was surgically treated, as there was no pregnancy after surgery, she was given intrauterine insemination with her husband's semen (IU) pregnancy was obtained, determined at 15 days of menstrual lack by presence of subunit B of HCG in serum and vaginal ultrasound that confirmed gestational sac. One month after she presented at Urgencies with an acute abdominal condition; laparotomy was done and salpingectomy was carried out for ruptured tubal pregnancy confirmed by histopathology. The evolution on intrauterine pregnancy was normal culminating with cesarean section at week 35 by inminence of eclampsia/Mother and child in good conditions. PMID- 1601315 TI - [Presentation of a mathematics formula of duplicated times of estradiol predictive for ovular harvesting]. AB - 30 patients were studied, that were included in the IVF program of the INPer. The estradiol response was studied and was correlated with the number of retrieved oocytes. The previously known E2 values considered as indicative for cancellation did no were observed in this series, and there are proposed new ones, also prognostic criterion for oocyte retrieval are proposed. PMID- 1601316 TI - [Multifactorial analysis of the blood levels of LH, FSH and estradiol in relation to ovular harvesting rates, fertilization and segmentation in patients undergoing assisted reproduction (GIFT-FIVTE)]. AB - This study shows that there is certain tendency to asssign more value to the observation of follicular growth by ultrasound than to hormonal levels "per se". However, the appreciation of growth is only part of the phenomenon of development and ovarian maturity, for that, surveillance with hormonal monitor of ovarian response keeps with a most important role in Assisted Reproduction Clinica. The basal levels, mainly of FSH and in a less degree LH, inversely correlate with the amount of retrieved ovocytes. Estradiol values should be interpreted with a fixed point of reference, as the day of HCG administration, and a direct relation is seen between estradiol levels and captured ovocytes; however, is of highest usefulness to value the conduct of estradiol level, with the knowledge that the prognosis for good capture rates improves with ascending values and above 700 pg in the day of HCG administration. PMID- 1601317 TI - [The use of prostaglandins for labor conduction in its latent phase]. AB - We wanted to know enprostil efficacy, an E2 prostaglandin analogous as a labor conductor in it's latent phase in term pregnancies. 188 patients were included, 52% received intracervical enprostil and 48% were treated with oxytocin. The labor evolution, resolution and complications were watch over. 15 patients (15.6%) of the study group required labor conduction with oxytocin because it was inhibited after peridural anesthesia. The main pregnancy resolution was vaginal via; only 6.3% of the study group subjected cesarean section against 10.3% of the witness group and the most frecuent indication was stationary dilation (1 and 8 cases respectively). The time of the latent phase and total labor was lower statistically in the study group. The observed complications were post-labor hemorrhage (3.1%), polysystolia (4.1%) and vomiting (5.2%), without significant difference with the witness group. We conclude that intracervical enprostil help cervical mature. shortenning latent phase and total labor, disminish oxytocin requeriment and cesarean incidence by cervical alterations without compromise maternal-fetal morbi-mortality. PMID- 1601318 TI - [Glucose determination as prognosis index of intra-amniotic infection]. AB - Intraamniotic infection is a frequent problem in Obstetrics, and is related with an important maternal and fetal impact, being important pre-term delivery and premature rupture of membranes. The "golden" test for this entity is bacteriological culture. Its use is limited in function of time (more than two days) and disponibility. The rapid diagnosis of infection in vital to start antimicrobial management and evaluation of uterine evacuation. Low concentrations of glucose (G) have been used as prognostic of infection in different biological compartments. The objective of this study is to evaluate the usefulness of G as prognostic index of intraamniotic infection (PIIAI) as compared with Gram tincture (GT) and bacteriological culture. Sixty four patients were included. Group I (n = 33) with infection, and group II (n = 31) without infection. Average of G for group I was 19.96 +/- 07.61 ES and 114.46 +/- 20.09 ES for the group II, with p less than 0.001. The sensitivity (S), specificity (Sp), positive predictive value (+PV) and negative (-PV) for a concentration of G in amniotic fluid less than 15 mg/dl was 72, 77, 77 and 72% respectively. The S, Sp +PV and PV for G minor than 10 mg/dl was 69, 87, 85 and 73%. Gram tinction had a S, Sp +PV and -PV of 57, 83, 79, 65%. If both determinations are put together (G and GT), one sees and S of 88%, Sp 77% +PV 80% and -PV 85%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601319 TI - [Identification and initial characterization of a protease of immunoglobulin A associated with human spermatozoa]. AB - The factors that the human semen use to block the humoral immune response at the uterine cervix level are not known. This response is mainly represented by immunoglobulin A, secretory type (IgAs). A possible mechanism would be hydrolisis od IgAs in an analogue ways as it has been described for some pathogenous bacteria that colonized human epitheliums and hydrolize IgAs. The objective of this study was to search for the presence of a protease for IgAs in human semen, seminal plasma and espermatozoons, using immunoelectrophoresis in agarose and electrophoresis in polyachrilamide, doing after immunotransference in nitrocellulose membrane. It was possible to identify a protease in sepermatic fraction, that hydrolizes IgAs, producing two fragments, the first one with molecular weight 66 to 70 kD, the degrees C. It is a metaloprotease (inhibited by EDTA). Its acti-enzymatic activity was optimal at 24 hours, pH 7.5 at 37 C. It is a metaloprotease (inhibited by EDTA). Its activity was specific for IgAs, and do not affected other immunoglobulins (IgG and IgM). The enzymatic activity of spermatozoon demonstrated in this study, may be on of the necessary factors used for blocking humoral immune response in femenine genital tract, and to permit that spermatozoon achieve the fecundation of human ovocyte. PMID- 1601320 TI - [The distribution of adipose tissue is related to the levels of insulin in the obese woman]. AB - We studied 51 patients aged 20-35 years, with overweight or obesity evaluated by the body mass index (BMI = weight height2) when it was higher than 25 (normal 20 25), and a control group of six women with the same age and normal BMI. In all patients waist and hip circumferences were measured, to calculate the waist/hip ratio (WHR). Also serum insulin was measured in basal conditions and as response to 75 g oral glucose load, taking samples at 30, 60, 90, 120 and 180 minutes after. The test were performed 3 to 6 days following a spontaneous or induced genital bleeding with progestin. The WHR showed a normal distribution with the greatest frequency at 0.87. The patients were classified with predominance of adiposity in the upper body segment, when the WHR was equal or more than 0.85, and with adipose predominance in the lower body segment when it was equal or less than 0.84. The average insulin values in response to oral glucose load of patients with upper body segment obesity were significantly higher (Mann Whitney's U = 0, p less than 0.02) than the corresponding cases with lower body segment obesity. Besides, there was a significant correlation between WHR and serum insulin values at 30 minutes after the oral glucose load (Pearson's r = 0.331, p less than 0.02). These results suggest a relation between the distribution of adiposity and insulin values, which were higher in patients with adipose predominance in the upper body segment. PMID- 1601321 TI - [Impact of the maternal age variable on ovular harvesting, fertilization and segmentation in a program of assisted reproduction]. AB - The increased maternal age was found as responsible for the ovaric biological failure, that in turn, becomes an altered hormonal response, and a reduction in the amount of susceptible ovocytes, susceptible for capture; this diminution in the amount of ovocytes, and not an intrinsic alteration in its quality is at the moment the biological translation of ovarian aging. Therefore, maternal age variable, with its ovarian and endometrial repercussion, becomes the variable with the greatest impact in Assisted Reproduction programs. The variable age is statistically independent from other variables as procedure indication, sterility type, used ovarian stimulation. The patients age should be considered as a very important prognostic factor, when proposing the methods os Assisted Reproduction, independently of the greater risk of gestation problems. PMID- 1601322 TI - Are dioxetanes chemiluminescent intermediates in lipoperoxidation? AB - Ultraweak chemiluminescence arising from lipoperoxidation has been attributed by several authors to the radiative deactivation of singlet oxygen and triplet carbonyl products. The latter emitters have been suggested to come from annihilation of RO. and ROO. radicals as well as from the thermolysis of dioxetane intermediates formed by (2 + 2) cycloaddition of 1O2 to polyunsaturated fatty acids. This article questions possible dioxetane intermediacy in lipoperoxidation, as the literature clearly states that addition of 1O2 to alpha hydrogen-containing alyphatic olefins yields only the corresponding allylic hydroperoxides. These compounds may undergo dark thermal or Lewis acid-assisted decomposition to the same product obtained from dioxetane cleavage. Here, reexamining the chemiluminescence properties of dioxygenated tetramethylethylene and linoleic acid and comparing them with those of tetraethyldioxetane, a hindered dioxetane, we corroborate the literature information that only steric hindrance leads to dioxetane formation upon singlet oxygen addition to electron poor olefins, albeit in very low yields. Proton nuclear magnetic resonance (1H NMR) analysis, quenching by dioxygen and energy transfer studies to 9,10 dibromoanthracene, as well as gas chromatography (GC) analysis of triphenylphosphine-treated and untreated photo- and chemically dioxygenated olefins support our final conclusion that dioxetane formation during lipoperoxidation can be safely excluded on the basis of the data presently available. PMID- 1601323 TI - Maintenance of left ventricular function (90%) after twenty-four-hour heart preservation with deferoxamine. AB - During 24-h in vitro heart preservation and reperfusion, irreversible tissue damage occurs caused by reactive oxygen intermediates, such as superoxide radicals, singlet oxygen, hydrogen peroxide, hydroperoxyl, hydroxyl radicals, as well as the peroxynitrite radical. Reduction of the related oxidative damage of reperfused ischemic tissue by free radical scavengers and metal chelators is of primary importance in maintaining heart function. We assessed whether deferoxamine (DFR) added to a cardioplegia solution decreased free radical formation during 24-h cold (5 degrees C) heart preservation and normothermic reperfusion (37 degrees C) in the Langendorff isolated perfused rat heart. The deferoxamine treated hearts were significantly (p less than .001) better preserved than the control hearts after 24 h of preservation with regard to recovery of left ventricular diastolic pressure, contractility (+dP/dt), relaxation (-dP/dt), creatine kinase release, and lipid peroxidation. DFR preserved cell membrane integrity and maintained 93% of left ventricular contractility. The evidence suggests that DFR reduces lipid peroxidation damage by reducing free radical formation and thereby maintaining normal coronary perfusion flow and myocardial function. PMID- 1601324 TI - Kinetics and site specificity of hydroperoxide-induced oxidative damage in red blood cells. AB - To provide a detailed description of the time course and the site specificity of hydroperoxide-induced oxidative stress in red blood cells (RBCs), we have characterized the action of a membrane-soluble (cumene hydroperoxide [cumOOH]) and a water-soluble (hydrogen peroxide [H2O2]) oxidant. The fluorescent polyunsaturated fatty acid (PUFA) parinaric acid (PnA) was used to probe peroxidation processes in the membrane, and oxidation of hemoglobin (Hb) was measured spectrophotometrically as an indicator of cytosolic oxidative stress. The observed degradation patterns of PnA and Hb were clearly distinct for each oxidant. At comparable oxidant concentrations, the cumulative oxidative stress on the RBC membrane was always much higher with cumOOH, whereas much more Hb oxidation was measured with H2O2. The kinetics of Hb oxidation as well as the nature of the products formed were different for each oxidant. The main Hb oxidation product generated gradually by cumOOH was metHb, whereas H2O2 caused the rapid formation of ferrylHb. CumOOH caused more oxidation of endogenous PUFAs and of vitamin E, while the degradation pattern of vitamin E closely resembled that of PnA. At high oxidant concentrations, extensive cell lysis was observed after prolonged incubation. Butylated hydroxytoluene (BHT) completely prevented oxidation of endogenous PUFAs but did not completely prevent hemolysis, indicating that factors other than lipid peroxidation are also important in causing lysis of RBCs. The action of cumOOH is characterized by a gradual reaction with Hb, generating radicals that produce an oxidative stress primarily directed at the membrane, which increases in time to a maximum and then gradually decreases. In contrast, H2O2 crosses the RBC membrane and reacts rapidly with Hb, generating a very reactive radical species that has Hb, not the membrane, as a prime target. H2O2-induced oxidative stress is at a maximum immediately after addition of this oxidant and decreases rapidly to zero in a short time. These findings provide further insight into the mode of action of hydroperoxides and the mechanism of compartmentalization of RBC oxidative damage. PMID- 1601325 TI - Role of reactive oxygen species in intestinal diseases. AB - It is well known that reactive oxygen metabolites are generated during several pathologies, and that they are able to disturb many cellular processes and eventually lead to cellular injury. After intestinal ischemia, reactive oxygen species are produced when the ischemic tissue is reperfused. The enzyme xanthine oxidase is thought to play a key role in this process. As a result of this oxygen radical production, the permeability of the endothelium and the mucosa increases, allowing infiltration of inflammatory leukocytes into the ischemic area. Moreover, reactive oxygen species are also indirectly involved in leukocyte activation. In turn, these inflammatory cells respond with the production of oxygen radicals, which play an important role in the development of tissue injury. Thus, intestinal ischemia and reperfusion evokes an inflammatory response. Also during chronic intestinal inflammatory diseases, reactive oxygen metabolites are proposed to play an important role in the pathology. Scavenging of reactive oxygen species will thus be beneficial in these disorders. PMID- 1601326 TI - The role of oxygen radicals in experimental acute pancreatitis. AB - Oxygen-derived free radicals mediate an important step in the initiation of experimental acute pancreatitis. Thereby, it seems that these reactive oxygen metabolites are generated at an early stage of disease. The source of the enhanced production of oxygen radicals still remains unclear. Experimentally, the efficiency of scavenger treatment varied between different models, whereby these differences depended on the experimental model and not on the form of pancreatitis which was induced. Most studies pretreated the experimental animals before inducing acute pancreatitis. This does not mirror the clinical reality, since patients are admitted to the hospital after onset of the disease. It was shown in Cerulein pancreatitis, however, that scavenger treatment also mitigated the pancreatic tissue damages after induction of acute pancreatitis. Moreover, antioxidant treatment also attenuated the extrapancreatic complications, thus improving the final outcome of the disease. The first indirect observations also suggest that in human acute recurrent and chronic pancreatitis, oxygen free radicals are generated and add to the damages seen. Therefore, well-defined controlled clinical studies with patients suffering from acute pancreatitis are needed to validate the role of oxygen radicals in this disease. PMID- 1601327 TI - Protection of DNA damage by dietary restriction. AB - Dietary restriction is known to retard the aging processes and delay the onset of age-related neoplastic diseases. The mechanisms underlying these remarkable actions of nutritional intervention are not known in spite of recently intensified research efforts. However, the last couple of years' research on dietary restriction produced strong evidence indicating that its effective antiaging actions might be related to its ability to modulate free radical damage. In the present study, DNA damage and attenuation of the damage by dietary restriction were assessed by measuring 8-hydroxydeoxyguanosine 8-OH dG) in both nuclear DNA (nuDNA) and mitochondrial DNA (mitDNA) fractions. The data show that substantially more damage (approximately 15 times) occurred in mitDNA compared to nuDNA. More interestingly, the DNA damage was significantly attenuated in dietarily restricted rats. PMID- 1601328 TI - Microbial strategies to prevent oxygen-dependent killing by phagocytes. AB - Microorganisms which are taken up by professional phagocytic cells of a host organism (e.g., by macrophages and polymorphonuclear leukocytes) encounter a series of antimicrobial events including confrontation with toxic oxygen species, derived mainly from the superoxide radical produced by phagocytic NADPH oxidase after uptake of the microorganism. Many microbes are susceptible to the oxygen dependent phagocytic stress and are efficiently killed. The strategies of some microorganisms to bypass an encounter with the phagocytes' reactive oxygen species, and biochemical systems contributing to the microbes' resistance to killing by reactive oxygen species are outlined. PMID- 1601329 TI - Intraperitoneal salvage chemotherapy in ovarian cancer: who is left to treat? PMID- 1601330 TI - Inhibitory effect of quercetin on primary ovarian and endometrial cancers and synergistic activity with cis-diamminedichloroplatinum (II). PMID- 1601331 TI - Mineral fiber exposure and the development of ovarian cancer. PMID- 1601332 TI - Characteristics of patients with small-volume residual ovarian cancer unresponsive to cisplatin-based ip chemotherapy: lessons learned from a Gynecologic Oncology Group phase II trial of ip cisplatin and recombinant alpha interferon. AB - The Gynecologic Oncology Group conducted a phase II trial of intraperitoneal (ip) cisplatin plus recombinant human alpha-interferon in patients with small-volume persistent/recurrent ovarian cancer. This study was based on the known single agent activity of the drugs administered by the ip route and experimental evidence of cytotoxic synergy between the agents. In 18 evaluable patients, only 1 partial response was observed (5.5% response rate). In an effort to explain these disappointing findings, patients were retrospectively divided into two groups; those with favorable disease (documented response to systemic platinum and absence of surgical findings of diffuse carcinomatosis at laparotomy prior to initiation of ip therapy) or unfavorable disease (no evidence of response to systemic platinum and/or laparotomy findings of diffuse carcinomatosis before ip treatment). The favorable patient population would be predicted to have a far greater chance of responding to local therapy, but only 3 of the evaluable patients fell into this category. In the 15 unfavorable patients, only 1 partial response was observed (7% response rate). We conclude that patients who have failed to demonstrate a response to systemic cisplatin or carboplatin or who have diffuse carcinomatosis at second-look laparotomy are poor candidates for second line ip cisplatin-based therapy, even if they are considered to have small-volume residual disease (each individual tumor nodules less than 0.5-1 cm). Such patients should be considered for alternative therapeutic strategies. PMID- 1601333 TI - Deoxycytidine protects normal bone marrow progenitors against Ara-C and gemcitabine cytotoxicity without compromising their activity against cisplatin resistant human ovarian cancer cells. AB - The intracellular metabolism and cytotoxic effects of Ara-C and 2' difluorodeoxycytidine (dFdC or Gemcitabine) administered with or without deoxycytidine (dCyd) were examined in cisplatin-resistant (2008/C13) and sensitive (2008) human ovarian cystadenocarcinoma cells. Compared to 2008 cells, 2008/C13 cells possess 2.1-fold higher glutathione (GSH) levels, enhanced expressions of GSH S-transferase (GST)-pi mRNA and protein, and significantly greater activity of GST, GSH peroxidase, and GST reductase. Although 2008/C13 cells were slightly cross-resistant to 4-hydroperoxycyclophosphamide, the drug displayed a steep dose-response (colony growth inhibition) effect toward these cells. 2008/C13 cells expressed greater sensitivity toward Ara-C and Gemcitabine. This was associated with intracellular Ara-CTP and dFdCtriphosphate levels in 2008/C13 significantly higher than those in 2008 cells. Against bone marrow progenitor cells, the cytotoxic effects of submicromolar levels of Ara-C or dFdC, produced in plasma following intraperitoneal administration of the drugs, were significantly reversed by cotreatment with high levels of dCyd achieved in plasma following intravenous administration. In contrast, the metabolism and cytotoxic effects of Ara-C and dFdC in 2008 and 2008/C13 cells were not significantly altered by dCyd concentrations that are reached in the peritoneum following intravenous administration. These in vitro data suggest that systematically administered dCyd might protect bone marrow progenitor cells against Ara-C cytotoxicity without impairing antitumor activity of intraperitoneal Ara-C. PMID- 1601334 TI - Vulvar destruction by malignant lymphoma. AB - Two cases of vulvar and perineal destruction by malignant lymphoma are described. The first case was of an untreated 4-year-long vulvar destruction due to a kappa positive lymphoplasmacytic lymphoma that ultimately resulted in the death of the patient. The second patient had involvement of the vulva and perineum by an angiocentric small and large mixed-cell lymphoma. Aggressive chemotherapy induced regression and healing of the lesions in the second case. Delayed diagnosis and inappropriate management of lymphomas in the vulva may lead to widely destructive disease of the lower female genital tract. PMID- 1601335 TI - Lymphoma of ovary with stromal luteinization, presenting as secondary amenorrhea. AB - A case of primary lymphoma of the ovary with extensive stromal luteinization is presented. Immunohistochemical markers that work satisfactorily in fixed tissues allowed a diagnosis of B cell lymphoma to be made on formalin-fixed tissue sections. Immunohistochemical analysis of frozen tissue and genotypic analysis confirmed the diagnosis of B cell lymphoma. By electron microscopy two populations of cells, including large atypical lymphoid cells and luteinized stromal cells, were identified. Presentation with amenorrhea and resumption of menstrual periods after removal of the tumor suggested the possibility of functional activity in the luteinized stromal cells. Stromal luteinization has not been previously described in primary ovarian lymphoma. PMID- 1601336 TI - Abstracts presented for the twenty-third annual meeting of the Society of Gynecologic Oncologists. March 15-18, 1992. PMID- 1601337 TI - Metatarsocuneiform arthrodesis for management of hallux valgus and metatarsus primus varus. AB - Sixty-seven closing wedge arthrodesis procedures of the first metatarsocuneiform joint were performed in 41 females and 12 males. Follow-up averaged 28 months (range 16-49 months) and was performed in 51 of 53 patients with a questionnaire, clinical examination, and comparison of pre- and postoperative weightbearing radiographs. The average hallux valgus angle was 34.5 degrees (range 20 degrees 75 degrees) and was corrected to 13.0 degrees (range-10 degrees-22 degrees) postoperatively. The average intermetatarsal angle was 14.3 degrees (range 9.5 degrees-34 degrees) and was corrected to an average of 5.8 degrees (range 0 degrees-12 degrees) postoperatively. Complications included seven superficial pin tract infections, three symptomatic dorsal bunions, one of which required repeat surgery, seven nonunions, one of which was symptomatic, one hallux varus, and three neuromas of the deep peroneal nerve. The range of motion of the hallux metatarsophalangeal joint was 85% of normal postoperatively. A total of 77% of the patients were totally relieved, 15% partially relieved, and 8% not relieved with respect to pain, comfort, appearance of the foot, and shoewear following surgery. The specific indications for performing this operation are discussed. PMID- 1601338 TI - Surgical treatment of clubfoot: a comparison of two techniques. AB - Between 1977 and 1989, 28 clubfeet were operated on, with follow-up ranging from 2 to 13 1/2 years and averaging 79 months. Group I (16 feet; average follow-up 104 months) underwent a modified Turco's posteromedial release. The functional result in this group was satisfactory in general, but approximately one third of this group required a secondary procedure for persistent intoeing or residual metatarsus adductus. Group II (12 feet; average follow-up 45 months) underwent a modified, complete subtalar release of McKay and Simons utilizing the Cincinnati incision. No patient in this second group required a secondary procedure. In our experience, the more complete subtalar release procedure of McKay and Simons resulted in better correction than the Turco posteromedial release. Although follow-up in group II was much shorter than that in group I, we felt that 2 years of minimum follow-up in group II was meaningful, since most of the recurrence or residual deformities were noticed within 18 months after surgery. The Cincinnati incision allowed better exposure and a more complete release. Skin flap necrosis was not a problem in this series. PMID- 1601339 TI - Anterior tibiotalar spurs: a comparison of open versus arthroscopic debridement. AB - We compared the difference in operative time, hospitalization and recovery time in two groups of patients who underwent open or arthroscopic resection of anterior, tibiotalar, impinging spurs. The operative time was approximately the same, but the average length of hospitalization and time to recovery were shorter in the arthroscopic group. A classification system is proposed that grades the degree of spur formation and assists in predicting the length of recovery time and whether the patient is a candidate for open or arthroscopic spur resection. In this series, grade I spur patients recovered and resumed full activity at 5.0 weeks, grade II at 5.6 weeks, grade III at 6.4 weeks, and grade IV at 10.0 weeks postoperatively. Grade IV patients are not suitable candidates for an arthroscopic debridement. PMID- 1601340 TI - The stabilizing role of the lateral ligament complex around the ankle and subtalar joints. AB - The stabilizing role of various ligaments in the lateral side of the ankle and hindfoot was examined experimentally and sequentially using 10 fresh amputated lower limbs. The anterior talofibular ligament contributed to ankle stability in plantarflexion and the calcaneofibular, the fibulotalocalcaneal, and posterior talofibular ligament in all positions. The lateral root of the inferior extensor retinaculum contributed to subtalar stability in neutral and dorsiflexion. The calcaneofibular, fibulotalocalcaneal, and cervical ligaments and the ligament of the anterior capsule of the posterior talocalcaneal joint and the interosseous ligaments contributed to subtalar stability in all positions. The subtalar joint accounted for upward of 50% of ankle/hindfoot inversion after ligament division in the intermalleolar plane. PMID- 1601341 TI - Circulatory disturbance of the first metatarsal head after Chevron osteotomy as shown by bone scintigraphy. AB - Distal osteotomies, such as Chevron osteotomies, have a potentially high risk for circulatory disturbance, since they transect part of the circulatory apparatus. An increased risk of up to 40% of avascular necrosis diagnosed radiographically has been reported when the osteotomy is combined with adductor tenotomy. On the other hand, new circulatory studies indicate that the circulation does not go in direct proximity to the adductor tendon. In this prospective study, 38 consecutive patients (41 feet) were randomized to Chevron osteotomy alone or Chevron osteotomy with adductor tenotomy. They were investigated 2 to 9 days postoperatively with 99mTc-methylene diphosphonate scintigraphy as well as x-rays and clinical examination. The average follow up was 19 months (range 12-48 months). Three defects were found in those operated with Chevron osteotomy alone, and one defect was found in a patient operated with Chevron osteotomy and adductor tenotomy. None of the patients had symptoms attributable to reduced circulation of the metatarsal head. Repeat scans showed healing in all four cases. Radiographs failed to show any signs of necrosis. Thus, Chevron osteotomy is a safe method in the treatment of hallux valgus which can be combined with adductor tenotomy without increasing the risk for circulatory disturbance. PMID- 1601342 TI - The intraosseous blood supply of the fifth metatarsal: implications for proximal fracture healing. AB - Fractures of the proximal fifth metatarsal can be divided into two distinct groups based on anatomical location and clinical course. Fractures of the tuberosity often heal well with nonoperative treatment, whereas fractures occurring in the proximal diaphysis (up to 1.5 cm distal to the tuberosity) have significantly increased risk for delayed union or nonunion. It is the purpose of this paper to describe the intraosseous vascular anatomy of the fifth metatarsal, and the clinical implications for basilar fracture healing. Ten fresh-frozen amputation or cadaver specimens were studied following arterial injection with India ink or barium sulfate suspension. The intraosseous blood supply to the fifth metatarsal tuberosity arose from numerous metaphyseal vessels penetrating the nonarticular surfaces of the tuberosity in a random, radiate pattern. The blood supply to the proximal diaphysis was derived primarily from the nutrient artery, which gave rise to longitudinal intramedullary branches. The arterial supply to the tuberosity joined the supply of the proximal diaphysis in the area just distal to the tuberosity, corresponding to the region of poor prognosis for fracture healing. This suggests that a relative lack of blood supply following a proximal diaphyseal fracture may contribute to delayed union and nonunion. PMID- 1601343 TI - An anatomic basis for recurrence after Morton's neuroma excision. AB - Dissections of the common digital nerve and its branches were performed in the second and third web spaces in five fresh-frozen cadaveric feet. Plantarly directed nerve tetherings, which were histologically demonstrated to be nerve branches, were consistently present along the course of each common digital nerve. These plantarly directed nerve branches were found in highest concentration in the distal aspect of the common digital nerve proximal to the bifurcation into the proper digital branches. The presence of these nerve branches may contribute to the high incidence of Morton's neuroma recurrence either due to traumatic neuroma formation in the branches or to failure of proximal retraction of the more distally resected nerve stump. PMID- 1601344 TI - Minimum incision surgery. PMID- 1601345 TI - Report on the 1989 American Orthopaedic Foot and Ankle Society Fellow Scholarship. AB - In 1989, the American Orthopaedic Foot and Ankle Society, Inc., sponsored a scholarship for a member to return to training to do a fellowship in foot and ankle surgery. The following is the account of Arthur Manoli, II, M.D., who served 3 months with Sigvard T. Hansen, Jr., M.D., at the Harborview Medical Center, University of Washington, Seattle, Washington, and 9 months with Marion C. Harper, M.D., at Vanderbilt University, Nashville, Tennessee. PMID- 1601346 TI - Sex determination of forensic samples by dual PCR amplification of an X-Y homologous gene. AB - Sex determination by polymerase chain reaction (PCR) analysis of the X-Y homologous amelogenin gene is highly reliable since the detection of an X specific amplified fragment validates the procedure. Previously, we reported that 250 ng of template DNA are required for sex determination by this method. We report here a refinement of the technique to include dual PCR. Dual PCR using two sets of primers results in the detection of X- and Y-specific amplified fragments from as little as 0.005 ng of template DNA. This is a powerful technique for the analysis of trace forensic samples and its application is discussed. PMID- 1601347 TI - DNA typing of forensic material with mixed genotypes using allele-specific enzymatic amplification (polymerase chain reaction). AB - Biological material in forensic casework frequently contains a mixture of genotypes, with a predominance of material from the victim and only trace amounts from the person committing the crime. Physical separation of the two genotypes or preferential lysis of different cell types may sometimes be possible. However, it is often difficult to achieve complete separation due to the lysis of cells or lack of material. We have developed an enzymatic amplification system for the HLA DQA1 locus, that will allow the presence of individual alleles in a sample with mixed genotypes to be determined, independent of their initial proportion in the sample. This system permits the identification of an allele representing less than 10(-4) of the background genotype. Use of polymerase chain reaction (PCR) with general primers allows only alleles representing more than about 1% to be detected, while the allele-specific amplification represents up to a 1000-fold increase in sensitivity. This method was applied to a rape case and a combined rape and murder case; in both cases the biological evidential materials contained a mixture of alleles from the victim and the rapist. Allele-specific PCR revealed the presence of alleles identical to those of the suspect using DNA from a vaginal swab taken after a rape incident, whereas by using general primers in the PCR only trace amounts of alleles other than those of the victim were found. Similarly, allele-specific amplification of DNA from vaginal swabs from the murder case revealed the presence of alleles identical to those of the suspect, while standard PCR only indicated the presence of genetic material from the victim. PMID- 1601348 TI - Sudden cardiac death: a comparative study of morphological, histochemical and biochemical methods. AB - The study deals with the comparison of morphological, histochemical and biochemical methods applied to the detection of myocardial infarction in 150 medico-legal autopsies performed at the Institute of Forensic Pathology in Copenhagen. The study also included an NBT (formazan) test of cardiac cross sections, and light microscopy and fluorescence microscopy of acridine orange stained specimens from four different sites of the cardiac musculature. Specimens of myocardium from the same four sites and pericardial fluid were analysed biochemically at the Institute of Legal Medicine in Granada. The K+/Na+ ratio was determined in the myocardial tissue and total creatine phosphokinase activity, creatine phosphokinase isoenzymes (MM, MB and BB) and myoglobin were assayed in pericardial fluid. When the results from Copenhagen and Granada were compared, there was absolute concordance in 96 cases, discrepancy in 53 and one case was inconclusive. After studying the circumstances of death, the number of discrepancies were reduced to 20, so that concordance was reached in 86% of all the cases. The results show that the combination of different methods leads to a diagnosis of myocardial infarction in far more cases than with morphological or biochemical methods alone. PMID- 1601349 TI - The reliability of cardiac haemodilution as a diagnostic test of drowning. AB - The diagnosis of drowning is one of the most challenging problems in forensic pathology. The estimation cardiac haemodilution is a simple method, but its use is limited by its lack of specificity and sensitivity. We have studied the limitations of this method and have defined the circumstances in which such a technique can be used. PMID- 1601350 TI - Efficacy of cerebro-spinal fluid biochemistry in the diagnosis of brain insult. AB - Postmortem biochemical indices may provide a useful adjunct to morphological studies in the identification of antemortem brain insult. We studied 34 routine medico-legal cases categorising them into one of four diagnostic groups. There were 11 cases of head trauma, 7 of 'hypoxia' (3 hangings and 4 carbon monoxide or drug poisonings), 7 sudden cardiac deaths and 9 miscellaneous cases. Survival time and postmortem interval was known for each case. The degree of cranio cerebral trauma was graded. Cerebro-spinal fluid (CSF) and vitreous humour were analysed for calcium, glucose, total proteins, aldolase, aspartate transaminase (AST), alanine transaminase (ALT), gamma glutamyltransferase (GGT), lactate dehydrogenase (LDH), creatine kinase (CK) and creatine kinase BB isoenzyme (CK BB). CK-BB was also measured in superior vena cava serum. In CSF there was a significant correlation between the severity of cranio-cerebral trauma and levels of aldolase, CK-BB, AST, ALT and total proteins. CSF CK-BB, median units/l (range), for the groupings of head trauma, hypoxia, sudden cardiac death and miscellaneous were respectively 823 (2-3431); 96 (2-187); 4 (2-25); 5 (1-69). Corresponding serum CK-BB levels were 240 (28-322); 390 (26-411); 180 (20-482); 79 (18-530). PMID- 1601351 TI - Sudden death from secondary massive pulmonary embolism derived from marrow emboli trapped by Chiari's network. AB - We report a case of fatal massive pulmonary embolism in an 86-year-old woman. The embolus occurred as a result of embolic bone marrow particles from a fractured femur becoming trapped by a Chiari's network which then acted as a source for propagation of a large thrombus which detached and caused sudden death from massive pulmonary embolism. To our knowledge this is the first report of such a case. PMID- 1601352 TI - Vomit identification by a pepsin assay using a fibrin blue-agarose gel plate. AB - Reported is a simple and reliable method for identifying the presence of gastric fluid in forensic samples by an assay that reveals the pepsin activity. These samples are usually vomit found at the scene of a crime, either in fresh form or as a dried stain on clothing. The pepsin within the sample is assayed for its proteolytic activity which is revealed in a fibrin blue-agarose gel plate, as a result of an enzymatic reactivity that takes the form of a concentric, blue, translucent ring around the tested sample. Apart from being able to determine the pepsin content of fresh or recent forensic samples, this method has also achieved positive reactions in aged gastric fluid stains that were kept at room temperature. No body fluids other than the gastric fluid and no proteolytic enzymes other than pepsin show a positive reaction with the use of this method. This method has an additional advantage, in that the enzymatic activity seen on the gel plate can be photographed and the gel plate, on drying, can also be preserved as evidence. PMID- 1601354 TI - Chloral hydrate overdose: trichloroethanol detection by gas chromatography/mass spectrometry. AB - A case is presented where an individual ingested a fatal dose of chloral hydrate. Trichloroethanol (TCE), the metabolite of chloral hydrate, was initially identified by the Fujiwara reaction and quantified by gas chromatography/mass spectrometry in blood )127 mg/l), urine (128 mg/l) and stomach contents (25 mg total). PMID- 1601353 TI - Distribution of malathion in body tissues and fluids. AB - Six cases of suspected poisoning were studied. The various body tissues and fluids of all the cases were analysed and malathion was found positive. The quantitative analysis was performed using high performance liquid chromatography. The distribution of malathion was studied in lungs, liver, kidneys, spleen, brain, heart, blood, muscles, urine and gastric contents. PMID- 1601355 TI - [An error? Consent for an AIDS test was obtained afterward]. PMID- 1601356 TI - [Quality assurance in ambulatory care. Viewpoint of the forensic expert for concentrated action in public health]. AB - FUNDAMENTALS: Assuring the quality of medical care is a self-imposed obligation on the part of the profession and, at the same time, a legal obligation. MAIN TOPICS: On the way to implementing this requirement, the following points must be taken into account: the measurability of the quality of medical care, establishment of the quality of structure, treatment and results, aids for the determination and documentation, remuneration, and the motivation for implementing quality control. CONCLUSIONS: A further development of present day approaches to quality assurance resulting in returning to the physician more responsibility while putting on him the onus of proof, would be desirable. PMID- 1601357 TI - [Carpal tunnel syndrome. The most frequent pressure-induced peripheral nerve lesion]. AB - Carpal tunnel syndrome is the term given to compression neuropathy of the median nerve in the carpal tunnel. It is the most common pressure-induced peripheral nerve lesion. It is typically associated with numbness of the index, long and ring fingers, and nocturnal brachialgia. The diagnosis is supported by the typical clinical symptomatology and the positive Hoffmann-Tinel sign, and is confirmed by the electroneurographic examination (ENG) of the median nerve, which can also be used for follow-up monitoring. During surgery, careful inspection and palpation of the carpal tunnel must be performed to detect such conditions as synovitis, anatomical variants and tumors. PMID- 1601358 TI - [Structures of the knee joint in nuclear magnetic resonance tomography. Improved representation with 3D volume imaging]. AB - Despite 3D gradient echo technique has a better spacial resolution than spin echo sequences, 3D imaging is not well accepted for clinical routine. Because of the large amount of data evaluation cannot be done by single photo-documented slices. Postprocessing of the 3D data sets with an image analysis system is indispensable. A maximum of two different gradient echo sequences (FLASH, FISP) are necessary for imaging of the whole interesting volume with continuous slices. Time of examination is shorter (16 resp. 32 minutes) compared with conventional spin echo sequences. In our opinion 3D gradient echo-sequences are a reliable noninvasive technique for the evaluation of pathological changes of the knee joint which could replace diagnostic arthroscopy in the future. PMID- 1601359 TI - [Increased expression of growth factors following angioplasty. Restenosis by stimulation of vascular smooth muscle cells]. PMID- 1601360 TI - [New guidelines for fracture treatment. 3: The upper extremity]. PMID- 1601362 TI - [What does treatment of HIV infected patients cost?]. PMID- 1601361 TI - [Dyslipoproteinemia and diabetes mellitus in a metabolic syndrome]. AB - AIMS: Presentation of important aspects of the metabolic syndrome, taking diabetes mellitus and the metabolic status in advanced age as an example. MAIN TOPICS: The metabolic syndrome represents a combination of diabetes mellitus, dyslipoproteinemia, adiposity, hypertension, and hyperuricemia, together with the sequelae of atherosclerosis, fatty liver and gallstones. In industrialized countries it is considered the most common metabolic sequela of affluence. Owing to the complexity of the disorders presenting, treatment must not be limited to normalization of glucose metabolism. In addition to dietetic and physiotherapeutic measures and anti-diabetic agents, treatment with lipid lowering agents is also necessary. Since a main feature of disordered lipid metabolism, is hypertriglyceridemia, fibrates in particular are indicated. These lower not only the triglycerides, but also elevated fibrinogen levels, and, in the case of fenofibrate, uric acid levels. Glucose tolerance remains unaffected. PMID- 1601363 TI - [Fetal HIV test not currently possible]. PMID- 1601364 TI - [Trans-fatty acids and lipids]. AB - AIMS: Description of the effects of major cis and trans fatty acids on serum lipoproteins. MAIN POINTS DISCUSSED: Trans fatty acids are formed in particular during industrial hydrogenation of oils and fats. Elaidic acid, the most important of the trans fatty acids, has an unfavorable effect on lipid metabolism that results in a negative shift of the HDL/LDL quotient. Nevertheless, due to the low concentrations in a balanced diet, its effects are only slight, and fall within the biological range of fluctuation. CONCLUSIONS: The biological effect of fatty acids varies from one class to another (saturated, mono-unsaturated, poly unsaturated). A more accurate differentiation would be desirable. On the other hand, the overall effect of the trans isomers of fatty acids on the organism as a whole is small, so that it does not need to be discussed, for example, in dietary counseling. PMID- 1601365 TI - [Anus praeter--site, care and corrective possibilities]. AB - BASIC REMARKS: The main indication for an colostomy is a carcinoma low down in the rectum. Apart from this, tumors in any part of the bowel or neighboring organs, and complications of inflammatory disease may make a diversion of feces necessary. POINTS DISCUSSED: A stoma should be sited at a distance from skin folds, and bony protuberance, and should be readily visible for self-care. Temporary "continence" can be achieved with special stool regulatory measures (in particular irrigation), while the patient can make to with a stoma cap or a mini bag. Many complications of stoma, in particular necrosis, parastomal hernias, prolapse, too large a stoma, stenosis and stomal recurrent tumor can usually be eliminated by surgery. CONCLUSIONS: Today excellent possibilities of stomal care are available for a wide range of problems, which can be determined and applied in cooperation with the various specialists. PMID- 1601366 TI - [Computer expert system for diagnosis of joint pain. Differential diagnosis per computer anamnesis]. PMID- 1601367 TI - [Spectrum of indications for flexible bronchoscopy. Importance in a general hospital]. AB - Fiberbronchoscopy is an extremely safe procedure carrying only minimal risk to the patient. Diagnostic application may include a transbronchial biopsy, brushing, and bronchoalveolar lavage. The indications for therapeutic bronchoscopy are, in particular, targeted irrigation and aspiration, extraction of foreign bodies, and hemostasis. Diagnostic and therapeutic indications are demonstrated in a number of cases. PMID- 1601368 TI - [Stress fractures of adolescents in sports]. PMID- 1601369 TI - [New guidelines for treatment of fractures. 4: Lower extremity]. PMID- 1601370 TI - [Long-term antihypertensive therapy of diabetic patients with felodipine. Effects of treatment on blood pressure and kidney function parameters]. AB - AIMS: Detection of possible effects on renal function parameters of long-term antihypertensive treatment administered to patients with diabetes mellitus. STUDY DESIGN: Prolongation of an open trial, initially planned for one year, on the effect of felodipine 10 mg/day in diabetics (Fortschr. Med. 109 (1991), 53-56). Continued treatment of 7 hypertensive insulin-dependent diabetics (mean age 58 +/ 3 years, HbA1 8.2 +/- 0.3%) over a period of between 24 and 32 months. RESULTS: The lowered blood pressure (from 160/94 to 150/82 mmHg; p less than 0.05) persisted. In the first 6 months of treatment, urinary albumin excretion (UAE) remained constant. Thereafter it increased (p less than 0.05 as compared with the figure seen after 6 months' treatment) to a degree that varied from one patient to another; overall, the UAE figures showed a relatively large intra-individual fluctuation during long-term therapy. Metabolic parameters remained uninfluenced by felodipine. CONCLUSIONS: It cannot be excluded that progression of diabetic renal disease cannot be adequately prevented by long-term treatment with calcium antagonists such as felodipine. PMID- 1601371 TI - [Generalized tendomyopathy]. AB - Generalised tendomyopathy (fibromyalgia) is characterised by diffuse localized pain involving the locomotory system, tenderness in the regions of the tendon insertions and muscles, loss of muscular power, sleep disorders and other vegetative functional and psychological disorders. In many cases, the diagnosis is delayed, often being made only after comprehensive superfluous diagnostic procedures, sometimes invasive, and inappropriate treatment. Age at disease onset is about 35 years, and initially involves, usually localized, the cervical or lumbar region of the spine. The condition is usually progressive over years. Pathogenesis is multifactorial; for generalization and persistence of the disease, psychosocial factors and civilization-related phenomena appear to play a decisive role. Treatment of generalized tendomyopathy is, for the most part, symptomatic and, overall, unsatisfactory. By way of medical treatment, only antidepressants seem to have a certain positive effect in some of the patients. Of importance is a good doctor--patient relationship and successful motivation of the patient to undergo active physiotherapeutic--in some cases also psychotherapeutic--treatment. With an eye to instituting more successful therapeutic measures and avoiding unnecessary diagnostic and therapeutic procedures, and, last but not least, for socioeconomic reasons, early diagnosis is of great importance. PMID- 1601372 TI - [Holistic treatment of generalized tendomyopathy. Therapeutic task of naturopathy]. PMID- 1601373 TI - [Generalized tendomyopathy--often misdiagnosed in clinical practice]. PMID- 1601374 TI - [Short stature as a risk indicator for coronary patients]. AB - BACKGROUND: Short stature as an indicator of coronary disease in German men is described. PATIENTS AND METHODOLOGY: A total of 4,524 patients investigated by coronary angiography (history of myocardial infarction and at least one vessel greater than or equal to 75% stenotic or occluded on angiography and, in addition corresponding levocardiographic changes) and 722 age-matched test subjects with unremarkable coronary angiographic findings were admitted to the study. RESULTS: The patients with coronary heart disease were, on average, 1.9 cm shorter than those with unremarkable blood vessels. This difference in height was found in particular in the age group between 40 and 60 years old. The reason for this is not known. PMID- 1601375 TI - [Recurrent calculus ileus of the small bowel. A diagnostic problem]. AB - Occlusion of the lumen by gallstones must be considered a rare cause of small bowel ileus; diagnosis and clinical symptoms have only sporadically been reported. The present paper shows that, in addition to gallstones, coproliths may also cause small bowel ileus, giving rise to identical clinical symptoms. For this reason, pre-operative diagnostic work-up should differentiate concretions in gallbladder and small bowel with respect to size, shape, consistency and X-ray contrast. If the stone proves to be a coprolith, the stenotic segment of bowel should be resected to prevent recurrences, while in the case of a gallstone, its manual manipulation across Bauhin's valve into the colon suffices. PMID- 1601376 TI - [Pneumonia diagnosis in persons infected with HIV]. PMID- 1601377 TI - [Improved diagnosis of endometrial cancer]. AB - Over the last few decades, carcinoma of the endometrium, the most common genital carcinoma in women, has become more and more important. For a long time, intensive efforts to improve its early detection remained unsuccessful. Not until the introduction of vaginal ultrasonography was a decisive step forward achieved in the early detection of this carcinoma on the basis of an assessment of endometrial thickness. In clinical studies, measurement of endometrial thickness by intravaginal ultrasonography has proved an outstanding parameter for the early detection of endometrial neoplasia, even in asymptomatic postmenopausal women. PMID- 1601378 TI - [Fertility disorders in the male. Part 2: Therapeutic possibilities]. AB - In Part 1 of this paper, the various diagnostic procedures employed to establish the fertility status of the male are described. Apart from the important aspect of psychological counseling offered the couple, therapy includes surgical, including microsurgical procedures, and medicinal treatment. The possibilities of causal pharmacological treatment of disordered spermatogenesis are limited, while in the case of disturbances affecting the epididymis and other adnexa this approach is frequently successful. In the fertility clinic, endocrinological diseases are of only minor importance. PMID- 1601379 TI - [Duration of work incapacity before and after inpatient therapeutic procedures]. AB - An analysis has been made of days off work prior to and following a course of treatment in clinics for rehabilitation. A comparison of pre-treatment and after treatment three-year periods revealed a small decrease of 8 days (9.2%). The youngest age group had the most time off work and--measured in terms of days off work--also the greatest response to treatment. Also after post-hospital rehabilitative treatment clear, though not statistically significant, reductions in the number of days off work were observed. The most striking changes were seen when (only) total number of working days lost prior to the course of treatment was recorded: in the case of high pre-treatment figures for working days lost, a considerable decrease was subsequently observed, while in the case of low working days lost figures, a marked increase in days off occurred. With respect to some of the groups participating, the methodological approach we employed did not make it appear probable that (measured in terms of total working days lost) these groups were "more pathological". It must be pointed out that these results were obtained in relatively small groups; it was not possible to extend the investigation. PMID- 1601380 TI - [Risk of HIV transmission to health personnel is greatest before noon]. PMID- 1601381 TI - [New guidelines for fracture treatment. Part 1: Principles of surgical treatment of fractures]. PMID- 1601382 TI - [Encephalitis lethargica--a neuropsychiatric disease]. AB - Encephalitis lethargica is presented as an exemplaric neuropsychiatric illness. Its history, the symptoms and the diagnostics, as well as its pathology and therapy are illuminated. Finally, specific problems and questions with regard to encephalitis lethargica are discussed: the question of a viral genesis and of a probable reappearance of the apparently disappeared encephalitis lethargica, the problems concerning the account for the neurological and psychiatric symptoms, and the question of role and function of the basal ganglia. PMID- 1601383 TI - [Evaluation of psychiatric treatment by patients--a study of assessment and stability over time]. AB - The principal results and methodological problems of the Anglo-American research on patient's satisfaction with psychiatric treatment are summarised. This study aimed at investigating whether simple quantitative and qualitative methods to assess the patient's view of treatment yield similar results, and to which extent that view changes over time. 53 patients in a community care system were questioned on their view of treatment twice with a period of 20 months between the two interviews. Visual analogue scales and open questions were used for assessment. On the average, the patients' views of treatment as a whole and of different aspects were positive. There was no significant correlation between the patients' views at the two points of time. Patients' view was related to psychopathological symptoms and changed along with changes of symptoms over time; patients with more severe symptoms expressed a more negative view and wished more changes of treatment. Consequences of the findings for assessment of psychiatric treatment via the patients' view are discussed. PMID- 1601384 TI - [Function of oncogenes in neuroepithelial tumors]. AB - The human genome contains so-called protooncogenes which can be activated to oncogenes by mutations. Oncogenes contribute to the development of tumours of the nervous system. Some of the oncogenes are related to growth factors or to cytogenetic changes in tumours. A survey is given of current research on oncogene loci in neuroepithelial tumours by recombinant DNA techniques. In neuroblastomas the amplification of the oncogene N-myc is associated with a poorer prognosis. In neuroepithelial tumours the amplification of c-erbB, which is in part homologous to the epidermal growth factor receptor gene, is restricted to malignant neoplasias. An enhanced expression of the oncogene c-sis, which codes for the platelet-derived growth factor, is found in 85% of malignant gliomas. Many studies of relatively fewer cases suggest the influence of other, further oncogenes in the group of neuroepithelial tumours. PMID- 1601385 TI - [Importance of the hippocampus and parahippocampus with reference to normal and disordered memory function]. AB - For decades there have been differing, partly controversial ideas concerning the function of the hippocampus. They were newly stimulated by the discovery of the widespread neocortical connexions of the adjacent parahippocampus, which itself is closely interconnected via its anterior part with the hippocampus. All theories have in common that they conceive these areas to be sites for the integration of complex information. However, some of the observations regarding their role in various memory functions are very contradictory. The present article gives a survey of the current state of knowledge concerning anatomy, physiology and pathophysiology of these cerebral areas. It appears that hippocampus and parahippocampus play a significant part in the regulation of selective attention and expectation. Thus they might also influence the process of comparison and valuation which modulates the access to neocortical associative information stores. PMID- 1601386 TI - [CO2 test with transcranial Doppler sonography in cerebral ischemia]. AB - We evaluated the CO2-induced vasomotor reactivity of the cerebral vasculature in 48 patients with high degree stenosis or occlusion of the internal carotid artery by transcranial Doppler ultrasonography measuring changes of flow velocities in the middle cerebral artery. Further, the vasomotor reactivity of the basilar artery was measured in 48 patients with vertebro-basilar ischemia. These results were compared with the findings in normal individuals. The vasomotor reactivity was significantly reduced in patients with stenosis or occlusion of the internal carotid artery as compared to normal controls. In patients with high degree ICA stenoses, undergoing to carotid surgery, CO2-test showed a significant improvement of the pathological vasomotor reactivity 6 month after the operation. In the group of patients with vertebro-basilar ischemia, the vasomotor reactivity measured in the basilar artery, was significantly reduced in patients with completed brainstem infarctions but not in patients with transient brainstem ischemia or infarctions in the posterior cerebral artery territory. We conclude that evaluation of the cerebral vasomotor reactivity by transcranial Doppler ultrasound is able to identify an inadequate cerebral blood supply and may help to estimate the hemodynamic effect of stenosis or occlusion of the extracranial brain supplying arteries. PMID- 1601387 TI - Metabolic feedback in mammalian endocrine systems. AB - Information processing through feedback loops is an integral part of most endocrine systems, and ranges from simple negative loops to complex combinations of negative and positive loops. Moreover, feedback may occur at local (paracrine) or long-distance sites, and with multiple time-domains. Traditionally, feedback is visualized as one hormone stimulating release of a second hormone, which then circulates in the blood to carry out various biological activities, one of which is to inhibit further secretion of the first hormone. This represents a fail-safe mechanism to protect the organism against the potentially damaging effects of uncontrolled secretion of many of the common hormones, some of which are highly catabolic or anabolic. However, it is becoming increasingly apparent that the products of catabolism and anabolism may themselves participate in the feedback process in either a feed-forward or feedback manner. For example, free fatty acids are liberated by the action of growth hormone, and in turn are potent inhibitors of growth hormone secretion (feedback). On the other hand, stress activates adrenal cortical and medullary secretion, which also promotes lipolysis, but in this case the liberated free fatty acids may actually stimulate the system further (feed-forward). Similarly, glucose has been shown to directly inhibit the activity of several different endocrine pathways, and must now be considered an integral part of the overall regulatory mechanism involved in fine tuning secretion and possibly production of hormones. By constructing models of feedback of increasing complexity, it is possible to make predictions about previously unrecognized relationships between hormones and products of metabolism. PMID- 1601388 TI - Expression of c-myc and c-fos protooncogenes in the anterior pituitary gland of the rat. Effect of estrogen. AB - Thymidine incorporation into the DNA of the anterior pituitary gland is stimulated by estrogen. We studied the relationship between this effect and expression of the protooncogenes c-myc and c-fos. Within one hour after estrogen administration, the level of c-myc and c-fos mRNA increased in the anterior pituitary gland and remained high throughout the experimental period (16 to 22 hrs). Transcription of the prolactin gene, one of the targets of estrogen action, was stimulated at the same time intervals. There were no modifications in the growth hormone mRNA level. Thus, estrogen induced the expression of c-myc and c fos in the anterior pituitary gland in an early period. PMID- 1601389 TI - Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. AB - Studies were performed to obtain evidence for glyconeogenesis from pyruvate to the triose phosphates in pancreatic islets. Inability to show this evidence would be consistent with the fact that glyceraldehyde, but not pyruvate, is a potent insulin secretagogue. Synthesis of 14C-labelled glucose from 14C-labelled pyruvate could not be detected. Since this might have been due to lack of sensitivity required to measure 14C-glucose production in such a scarce tissue as islets, cDNA probes were used to estimate the relative expression of genes coding for gluconeogenic enzymes. Islets expressed pyruvate carboxylase mRNA, but even islets from rats which had been starved (a condition which induces phosphoenolpyruvate carboxykinase (PEPCK) in liver, kidney and adipose tissue) showed no PEPCK mRNA. This is consistent with our previous work showing the absence of PEPCK enzyme activity in islets. Therefore, islets can convert pyruvate to oxalacetate, but since they lack PEPCK, neither the beta nor alpha cell can convert oxalacetate to phosphoenolpyruvate and carry out glyconeogenesis. Pyruvate carboxylase mRNA was increased in islets that possessed the capacity for glucose-induced insulin release versus islets that lacked the capacity to respond to glucose, such as islets from fed rats (versus starved rats) and in islets cultured at a high concentration of glucose (versus at low glucose). Pyruvate carboxylase, therefore, must be involved in pyruvate metabolism and not glyconeogenesis in the pancreatic islet. PMID- 1601390 TI - The effects of fasting and refeeding on liver glycogen synthase and phosphorylase in obese and lean mice. AB - The responses of hepatic glycogen synthase and phosphorylase to fasting and refeeding were assessed as part of an investigation into possible sites of insulin resistance in gold thioglucose (GTG) obese mice. The active forms glycogen synthase and phosphorylase (synthase I and phosphorylase a) and the total activity of these enzymes were estimated in lean and GTG mice over 48 h of food deprivation, and for 120 min after glucose gavage (1 g/kg wt). In lean mice there was a maximal reduction in hepatic glycogen content after 12 h of starvation and the activity of phosphorylase a decreased from 23.8 +/- 1.9 to 6.8 +/- 0.7 mumol/g protein/min. These changes were accompanied by an increase in the activity of synthase I (from 0.14 +/- 0.01 to 0.46 +/- 0.04 mumol/g protein/min). In obese mice, similar changes in enzyme activity occurred after 48 h of starvation. These changes were accompanied by a significant reduction in the hyperinsulinemia and hyperglycemia of the GTG mice. After glucose gavage in both lean and obese mice, the activity of synthase I further increased over the first 30 min and declined thereafter. The activity of phosphorylase a increased progressively after refeeding. Results from this study suggest that despite increased hepatic glycogen deposition, the responses of glycogen synthase and phosphorylase, in livers of obese mice, to fasting and refeeding are similar to those of control mice even in the presence of insulin resistance. PMID- 1601391 TI - Life-long effect of a single neonatal treatment with estradiol or progesterone on rat uterine estrogen receptor binding capacity. AB - Rats treated with a single dose of 17 beta-estradiol or progesterone within 24 h of birth were subjected to ovariectomy at 8 weeks of age and were nine days later examined for the binding capacity of the uterine estradiol receptors by saturation and competition tests (with diethylstilbestrol used as competitor). The Bmax value of the neonatally estradiol-treated rats (6.78 x 10(-10) M) was significantly decreased relative to the control (1.99 x 10(-9) M). The competition analysis affirmed these results. Neonatal progesterone treatment also accounted for a significant decrease (1.25 x 10(-9) M) in receptor concentration relative to the control (1.66 x 10(-9) M). Considering the competition analysis the decrease was less than in the case of estradiol and not even significant by saturation analysis. The uterine mass did not differ between the experimental and control rats, but part of those treated with estradiol developed ovarian cysts. It follows that not only synthetic steroids (DES, allylestrenol), but also an excessive presence of the physiological steroid hormone during the critical period of receptor maturation can account for a decrease in uterine receptor concentration in adulthood. PMID- 1601392 TI - Plasma non-cholesterol sterols in patients with non-insulin dependent diabetes mellitus. AB - Plasma plant sterol concentrations (an index of cholesterol absorption efficiency) and plasma lathosterol concentration (an index of cholesterol synthesis rate) were measured in 52 patients with non-insulin dependent diabetes mellitus (NIDDM) and 36 non-diabetic controls. Plasma plant sterol concentrations were significantly (P less than 0.01) lower in diabetic patients (campesterol: men -36%, women -48%; betasitosterol: men -35%, women -42%). Fasting serum insulin levels were inversely correlated with plasma plant sterol concentrations in diabetic patients (campesterol: r = -0.347, P = 0.012; betasitosterol: r = 0.345, P = 0.012) and in non-diabetic men (campesterol: r = -0.578, P = 0.039; betasitosterol: r = -0.702, P = 0.008). Serum insulin levels were also correlated significantly with plasma lathosterol concentration in diabetic patients (r = 0.295, P = 0.034). The results of this study suggest that absorption of plant sterols and possibly cholesterol from the diet may be reduced in hyperinsulinemic diabetics. PMID- 1601393 TI - Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus. AB - Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/ 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601394 TI - Bioactive and immunoactive prolactin levels after TRH-stimulation in the sera of normal women. AB - The availability of an improved microbioassay for lactogenic hormone measurement has enabled comparison of basal and dynamic prolactin bioactivity (BA) and immunoactivity (IRMA) in normal human serum. Serum from 16 normal females aged 22 74 years was assayed and revealed a mean BA/IRMA prolactin ratio of 1.6 for basal and 1.8 for peak TRH-stimulated levels. Basal prolactin levels in postmenopausal women measured by bioassay were lower than in premenopausal women showing a relative and absolute decrease in prolactin bioactivity with age, but there was no significant difference in dynamic levels. There was also no significant difference in BA or IRMA levels following the stress of venepuncture. These findings indicate that, as previously described for basal levels, there is a good correlation between dynamic prolactin bioactivity and immunoactivity in human serum. PMID- 1601396 TI - Concentrations and adenine metabolic rates of adenine nucleotides in mononuclear cell populations of type I (insulin-dependent) diabetic individuals in different states of metabolic compensation. Preliminary results. PMID- 1601395 TI - Episodic thyrotropin (TSH) and prolactin (PRL) secretion during aging in postmenopausal women. AB - While aging is known to decrease episodic thyrotropin (TSH) secretion in men, no detailed information is available as to age-related alterations in the TSH and prolactin (PRL) release patterns in postmenopausal women (PMW). Accordingly, we compared the TSH and prolactin (PRL) secretory profiles of 6 euthyroid younger PMW (mean age: 53.0 years) with those of 7 euthyroid older PMW (mean age: 80.4 years). In all PMW, blood samples were obtained at 10 minute intervals for 10 hours for serial determinations of TSH and PRL by RIA. While thyroxine (T4) serum concentrations were not different in younger from older PMW, triiodothyronine (T3) levels markedly (p less than 0.05) decreased in older PMW. In both younger and older PMW, TSH and PRL were secreted episodically (by Cluster pulse algorithm), with considerable inter-individual variabilities in either study group. TSH and PRL pulse attributes (interpulse intervals, frequencies, amplitudes) were comparable in younger and older PMW, although a tendency of mean TSH to increase (p = 0.18) was noted for older PMW. Mean TSH and PRL serum concentrations were positively (r = 0.94, p less than 0.01) correlated in older, whereas not in younger PMW. These observations demonstrate that the pulse characteristics of episodic TSH and PRL secretion are preserved in PMW even of old age. However, in view of markedly decreased circulating T3 concentrations and of no substantial change in the TSH pulsatile secretion in older PMW, the negative feedback on the hypothalamic-pituitary unit may be impaired in elderly women. PMID- 1601397 TI - Effect of maintenance glucose concentration and length of culture on the glucose induced insulin response of isolated rat islets. PMID- 1601398 TI - Turf battles and the patients' best interests. PMID- 1601399 TI - A consumer-operated case management project. AB - The idea that patients and former patients might themselves be involved in service delivery has become increasingly popular in recent years. Once viewed as an expression of patient protest without clinical merit, self-help services are now, at least in some places, accepted and endorsed by mental health planning authorities. This month's guest columnists describe the philosophical underpinnings of a state-funded consumer-operated case management program in Oregon and discuss both the hope and some of the potential difficulties that such an experimental effort may generate. PMID- 1601400 TI - Therapy for an anxious patient who believes his symptoms are caused by a medical problem. PMID- 1601401 TI - Expressed emotion: conceptual, clinical, and social policy issues. AB - Research on schizophrenia has suggested an association between relapse of patients and high expressed emotion (EE), defined as criticism, hostility, or emotional overinvolvement of at least one family member. In international studies, however, the majority of families of persons with schizophrenia demonstrate low expressed emotion. These families are described as empathic, calm, and respectful by EE researchers, who also reject the idea of family schizophrenogenesis. The author discusses expressed emotion as a construct, its validity and stability over time, and the direction of the relationship between relatives' expressed emotion and patients' symptoms and behavior. She reviews studies indicating significant differences in levels of expressed emotion across cultures, examines the social policy implications of programming based on the construct, and suggests research on EE analogues in clinical and rehabilitative environments. PMID- 1601402 TI - Initial level of care and clinical status in a managed mental health program. AB - Data from 9,055 adult intakes performed over two and a half years of a managed mental health care demonstration project in a large U.S. city were used as indirect measures of quality of care. The level of care to which patients were initially assigned was examined in relation to the patients' clinical status as judged by both managed care case managers and treatment providers. During the period, assignment to inpatient care of patients in almost every clinical category decreased. The decrease seemed to reflect a policy decision to limit use of all inpatient services rather than a selective elimination of unnecessary hospitalization. Case managers rated a smaller proportion of patients severely disturbed, partial hospitalization was rarely used as an alternative to inpatient care, and detoxification services were increasingly used as an inpatient alternative. Although these data reinforce common beliefs about managed care, the quality of managed care programs can be accurately assessed only with data collected specifically for evaluation purposes. PMID- 1601403 TI - Are pretrial commitments for forensic evaluation used to control nuisance behavior? AB - The shift to dangerousness-oriented civil commitment criteria has led to speculation that mentally ill persons who do not meet those criteria are being hospitalized under criminal commitment statutes. Using data on patients' psychiatric symptoms at admission to a state hospital in Massachusetts, the authors retrospectively assessed whether patients charged with minor criminal offenses who were committed for evaluation of competence to stand trial would have met civil commitment criteria. The data suggest that most mentally ill patients who were criminally committed could have been civilly committed. However, a relatively greater proportion of persons with substance abuse, mental retardation, or other conditions who did not meet civil commitment criteria for mental illness were committed for pretrial evaluation. PMID- 1601404 TI - A mobile crisis program: collaboration between emergency psychiatric services and police. AB - An emergency psychiatry-mobile crisis program was established in 1987 in Charleston, South Carolina, linking professionals from the mental health center, the university, and the local police department. The program has two goals: to provide emergency psychiatric services to persons in the community and to train psychiatric residents in crisis intervention. Mental health staff act as consultants to the police in some situations, and in others the police provide security. The authors describe the development of the collaboration with police and important features of the program. Three cases illustrate how such collaboration can be of mutual benefit and can save lives. PMID- 1601405 TI - Emergency evaluation of adolescents. AB - Psychiatric emergencies faced by adolescents are often linked to developmental issues such as separating from parents, establishing attachments to peers, and developing autonomy. In a vulnerable adolescent, a stressful developmental event may trigger a pathological response--acute anxiety, depression with or without suicidal ideation or behavior, severe conduct disturbance, a first psychotic episode, or explosive or violent behavior--that requires emergency psychiatric treatment. The basic components of an emergency psychiatric evaluation of an adolescent include initial observation of the patient, taking a history, interviewing the patient and others accompanying the patient, conducting a mental status examination, making a diagnosis, and planning for disposition and further treatment. Such an evaluation may be the first contact with the mental health system for many adolescents, and the intervention of a sensitive clinician may help the adolescent be more comfortable seeking mental health care in the future. PMID- 1601406 TI - Management of the assaultive adolescent. AB - Evaluation and treatment of the assaultive adolescent is an important but difficult process. From a psychodynamic perspective, the author reviews factors associated with adolescent violence, including alcohol and substance use, depression and suicidality, overstimulation, sociocultural and family ambience, property damage, threats of violence, and alexythymia. Management and treatment issues are surveyed, such as the necessity to recognize that in some adolescents violence erupts not from narcissitic rage but from strong wishes for affectionate contact. Violent adolescents have little awareness of an inner psychological world, cannot name affects or differentiate one from another, and often confuse thought, feeling, and deed. In psychodynamic treatment, adolescents are helped to experience affect as part of themselves and to develop the capacity to manage affect and use it as a basis for communication and self-understanding. PMID- 1601407 TI - Family therapy in the treatment of adolescents. AB - A family with an adolescent must transform itself from a predominantly nurturant unit to one that can tolerate and encourage the adolescent's need to separate. When an adolescent presents with symptoms that disrupt the developmental process, the clinician who is familiar with several models of family therapy is better able to select a therapeutic and cost-effective intervention. For family assessments, the authors recommend a biopsychosocial approach, which has replaced the outdated view that families cause psychiatric problems and which acknowledges the family as a potential source of healing. The authors describe several models of family therapy--Satir's communication model, the structural model of Minuchin, Bowen's cross-generational model, and psycho-education--and examine features of these approaches useful for working with adolescents. Illustrative vignettes and some guiding principles for matching model and problem are offered. PMID- 1601408 TI - Building systems of care for youth with serious mental illness. AB - In 1990 the Robert Wood Johnson Foundation's Mental Health Services Program for Youth awarded grants to eight state-community partnerships to develop systems of care for mentally ill children and adolescents. The authors describe approaches to system building in the program's first two years of implementation. The evolving systems consist of government agencies in child welfare, mental health, public health, education, and juvenile justice, as well as private-sector health and mental health care providers. Basic system features include interagency steering committees and long-term intensive case management. Fundamental principles guiding system development are individualization of care to meet the needs of the specific child, organization of care to empower families to manage care over the long term, flexible financing of care, and normalization of care in family and community settings. PMID- 1601409 TI - The impact of divorce on adolescents. AB - A consensus that divorce constitutes a major disruption and disequilibrium in the lives of nearly all children is emerging. Reactions vary at different developmental stages. Divorce poses a very specific hazard to the normal adolescent process of emancipation from primary love objects. The author reviews recent research on the short-and long-term effects of parental divorce on adolescents, with special reference to adolescent developmental tasks. Treatment based on a psychoanalytic developmental perspective combined with a family systems approach is recommended. Careful attention should be paid to the gender of the therapist and the adolescent's developmental stage. Therapeutic modalities include individual and group therapy with the adolescent and conjoint therapy with the custodial parent, the single-parent family, and the noncustodial parent. The major goals of psychotherapeutic intervention with adolescents in divorced families are outlined. PMID- 1601410 TI - Mnemonics for eight DSM-III-R disorders. PMID- 1601411 TI - Recognition of alcohol abuse in psychiatric outpatients and its effect on treatment. PMID- 1601412 TI - Assessing competency. PMID- 1601413 TI - Assessing competency. PMID- 1601414 TI - Assessing competency. PMID- 1601415 TI - Assessing competency. PMID- 1601416 TI - Excessive documentation. PMID- 1601417 TI - Point mutations and polymorphisms in the human dystrophin gene identified in genomic DNA sequences amplified by multiplex PCR. AB - About one third of Duchenne muscular dystrophy (DMD) patients have no gross DNA rearrangements in the dystrophin gene detectable by Southern blot analysis or multiplex exon amplification. Presumably, in these cases, the deficiency is caused by minor structural lesions of the dystrophin gene. However, to date, only a single human DMD case has been described where a point mutation, producing a stop codon, accounts for the DMD phenotype. To screen for microheterogeneities in the dystrophin gene, we applied analysis by chemical mismatch cleavage to thirteen exons amplified in multiplex sets by the polymerase chain reaction. This analysis covers approximately 20% of the dystrophin-coding sequence. Sixty DMD patients without detectable deletions or duplications were investigated, leading to the identification of two point mutations and four polymorphisms with a frequency higher than 5%. Both point mutations are frameshift mutations in exons 12 and 48, respectively, and are closely followed by stop codons, thus explaining the functional deficiency of the dystrophin gene products in both patients. PMID- 1601418 TI - HLA haplotype segregation and ultrastructural study in familial immotile-cilia syndrome. AB - The immotile-cilia syndrome (ICS) is a congenital disorder characterized by dysmotility or even complete immotility of the cilia in the ciliated epithelia. The most frequent consequences include recurrent airway infections from early childhood. Neonatal asphyxia often occurs. Males are usually sterile, whereas females may be fertile or infertile. The disease is inherited as an autosomal recessive trait, but previous attempts to localize the ICS susceptibility gene have so far been unsuccessful. Here, we present the case of two sib pairs affected by ICS from two unrelated families. The electron microscopic investigation of nasal biopsies showed structural anomalies of the cilia, characterized by single microtubules or doublets, arranged randomly in the axoneme. Histocompatibility antigen (HLA)-genotyping of all family members revealed: 1) a significant association of ICS with the HLA-DR7; DQW2 haplotype, which is shared by all the affected sibs (P = 0.0099; RR = 25.94); 2) a possible linkage of the ICS susceptibility gene with HLA, both the affected sibs being HLA identical, the healthy brother in family B being HLA-different (sib-pair analysis: P less than 0.001). PMID- 1601419 TI - Pericentric inversion of chromosome 12; a three family study. AB - A pericentric inversion of chromosome 12 has been followed in three large independently ascertained Danish families. Out of a total number of 52 persons examined, 25 were found to carry the inversion. The breakpoints in all three families were localized to p13 and q13, resulting in more than one-third of the total length of the chromosomes being inverted. However, no chromosomal aberrations arising because of meiotic crossing-over inside the inverted area have been found among the offspring of the carriers. The percentage of spontaneous abortions among carriers is found to be high, viz. 33%. The segregation rate is calculated to be 0.58, which is not significantly different from an expected segregation rate of 0.5. In family 3, an additional inversion of a chromosome 9 has been found in 4 individuals. Our results are discussed in relation to previous findings and with respect to the genetic counselling of families with pericentric inversions. PMID- 1601420 TI - Missense mutations and the magnitude of functional deficit: the example of factor IX. AB - Some missense changes are compatible with normal protein function while others compromise essential aspects of protein maturation, specific activity, or stability. For those missense changes that alter function in the intact organism, how likely is it for the mutated protein to retain appreciable residual activity? By genetic analysis of patients with hemophilia B of known severity, this question can be addressed for missense mutations that reduce factor IX activity by fourfold or more below the average. We estimate that missense changes cause only 59% of moderate and severe disease, but these mutations are almost always (95%) of independent origin. In contrast, missense mutations are found in virtually all (97%) families with mild disease, but only a minority of these (41%) are of independent origin. From the aggregate data, we estimate that most (71%) of the independent deleterious missense mutations cause at least a 20-fold decrease in factor IX activity. PMID- 1601421 TI - Chromosomal findings in fetuses with prenatally diagnosed cysts of the choroid plexus. AB - Choroid plexus cysts were diagnosed in 25 out of 823 fetuses with prenatally diagnosed abnormalities (growth retardation/malformations). Among these, 5 revealed a chromosomal disorder (4 cases with trisomy 18 and one case with a translocation trisomy 21). Additional abnormalities, such as growth retardation, holoprosencephaly, hydrocephalus and club foot, were found in 6 out of the 20 fetuses with no chromosomal abnormality. All fetuses with a chromosomal disorder revealed further typical prenatally recognizable abnormalities. Our observation indicates that prenatally diagnosed choroid plexus cysts should be considered as an indication for prenatal chromosomal diagnosis, although the risk of there being an underlying chromosomal disorder is low in cases with no additional abnormalities. PMID- 1601423 TI - Direct estimate of the haemophilia B (factor IX deficiency) mutation rate and of the ratio of the sex-specific mutation rates in Sweden. AB - Mutation rates for X-linked recessive diseases have so far been estimated indirectly by postulating an equilibrium between the loss of defective genes caused by the low reproductive fitness of affected males and the gain resulting from new mutations. Here, for the first time, we directly estimate both the overall and sex-specific mutation rates for haemophilia B by detecting the gene defect of the families registered at the Malmo Haemophilia Centre. These represent a complete sample of the Swedish haemophilia B population (45 out of 77 pedigrees) and contain 23 families with a single affected male. Fifteen of these males had mothers available for study, and of these mothers, 13 had parents available for study. We show that 3 of the above patients and 10 of their mothers carry new mutations, and by extrapolation calculate that 8 males and 98 females should carry new haemophilia B mutations in the Swedish population (8.52 x 10(6) individuals). This leads to the following estimate of the mutation rates: overall mu = 4.1 x 10(-6); male specific nu = 2.1 x 10(-5); and female specific mu = 1.9 x 10(-6). The ratio of such male to female specific mutation rates is thus nu/mu = 11. PMID- 1601422 TI - Trisomy 8p: unusual origin detected by fluorescence in situ hybridization. AB - Chromosomal analysis of a neonate with brain and heart abnormalities revealed trisomy for 8p. The mother's karyotype showed 47 chromosomes with one chromosome 8 being represented as two separate chromosomes, an acrocentric 8p and a telocentric 8q. G-banding and silver staining revealed a satellite and nucleolus organizing region (NOR) on the 8p. Centromeric-specific probes to the centromeres of chromosomes 8, 15, 13/21, 22 and the acrocentric chromosomes revealed that only the 8q centromere was of chromosome-8 origin, while the 8p centromere was of chromosome-14 origin. PMID- 1601424 TI - Protease inhibitor (Pi) locus, fertility and twinning. AB - In a sample of 160 Dutch twin pairs and their parents, we found that mothers of dizygotic twins had frequencies of the S and Z alleles at the protease inhibitor (Pi) locus that were 3 times higher than a control sample. Mothers of identical twins also had a higher frequency of S than controls. The S allele may thus both increase ovulation rate and enhance the success of multiple pregnancies. There was also an increased frequency of the S allele in fathers of dizygotic twins; however, this may be a secondary effect of assortative mating for family size (indicating by the number of siblings of the parents), for which a correlation of 0.2 was observed. Parents of dizygotic twins came from larger families than parents of monozygotic twins, but no effect of Pi type on family size was seen. PMID- 1601425 TI - Mutation analysis of phenylketonuria in Spain: prevalence of two Mediterranean mutations. AB - We have screened seven Spanish phenylketonuric (PKU) families for the most prevalent Mediterranean and Caucasian mutations, and have subsequently found mutations P281L and IVS10. We have analyzed these two mutations in 23 of our patients. The frequencies found correspond to those of Mediterranean countries, such as Italy. This is the first report of a mutation analysis in the Spanish PKU population. PMID- 1601426 TI - The human gene (DSG3) coding for the pemphigus vulgaris antigen is, like the genes coding for the other two known desmogleins, assigned to chromosome 18. AB - Pemphigus vulgaris (PV) is a potentially lethal skin disease in which epidermal blisters occur as the result of the loss of cell-cell adhesion caused by the action of autoantibodies against a keratinocyte cell surface glycoprotein, the PV antigen (PVA). This latter protein is a member of the desmoglein subfamily of the cadherin superfamily of cell-cell adhesion molecules, present in the desmosome type of intercellular junction. The other two known desmogleins are DGI, which is a target antigen in another autoantibody-mediated blistering disease of the epidermis, pemphigus foliaceous, and HDGC, which is expressed in the basal layer of the epidermis and in the simple epithelium of, for example, the colon. Genes coding for DGI (DSG1) and HDGC (DSG2) have previously been assigned to human chromosome 18. We now present evidence, using a polymerase chain reaction assay, that DSG3, the gene coding for PVA, is assigned to the same chromosome. PMID- 1601427 TI - Gene frequencies of alcohol dehydrogenase2 and aldehyde dehydrogenase2 in Northwest Coast Amerindians. AB - The frequencies of the alleles encoding isozymes of alcohol dehydrogenase and aldehyde dehydrogenase were low in Northwest Coast Amerindians compared to Chinese subjects. PMID- 1601429 TI - Detection of a frequent polymorphism in exon 10 of the low-density lipoprotein receptor gene. AB - DNA sequencing of enzymatically-amplified exons of the low-density lipoprotein receptor gene from several individuals revealed a polymorphism in exon 10 of the gene. The codon for arginine 450 was converted from AGG to AGA in some alleles. PMID- 1601428 TI - Highly informative dinucleotide repeat polymorphism at the D11S29 locus on chromosome 11q23. AB - The informativeness of locus D11S29 as a genetic marker was improved by the identification of a highly polymorphic (GT)n repeat within the locus. Ten alleles were identified in parents of 40 Centre d'Etude du Polymorphisme Humain families and the polymorphism information content (PIC) was 0.77. The increased PIC value thus enables refinement of the linkage map of 11q23. PMID- 1601430 TI - DNA-fingerprinting: a further note on mutation rates. PMID- 1601431 TI - Strategy guidance and memory aiding in learning a problem-solving skill. AB - Guidance can help learners overcome the difficulties of getting started in a novel domain, but it is often ineffective in promoting learning and transfer. This article examines two aspects of guidance--communicating solution strategies for a problem domain and providing working memory support--in learning a novel problem-solving skill. Subjects in two experiments learned to troubleshoot simulated information networks. The learning environment varied in type of guidance provided--none, variable template, fixed template, and procedural instruction--and in availability of memory aiding. Variable-template guidance was effective when memory aiding was provided, and procedural instructions produced effective learning with or without memory aiding. However, fixed-template guidance was not effective, and there was no consistent effect of memory aiding in unguided, discovery learning conditions. The results have theoretical implications for the locus of guided-learning effects and suggest practical guidelines for the design of guided-learning environments. PMID- 1601432 TI - Retention of trained performance in consistent mapping search after extended delay. AB - We examined the retention of performance in memory, visual, and hybrid memory/visual search after subjects received extensive consistent mapping (CM) practice. In the first two experiments we examined retention of detection performance in memory scanning (Experiment 1) and in visual search (Experiment 2) approximately one month after training. In the third experiment we examined performance 1, 30, 90, 180, and 365 days following training on pure visual and hybrid memory/visual semantic-category search tasks. We examined retention at intervals up to one year after practice as a function of amount of CM practice. In addition, we assessed the degree of category activation (performance on untrained words from the trained categories) at each retention interval. Across experiments, we found no decay in CM trained memory search and minimal decay in pure visual search. Significant decline in CM performance was largely attributable to performance in the hybrid memory/visual search conditions. These data reconcile previously equivocal retention results for CM trained search performance. PMID- 1601433 TI - Temporal patterns of trunk muscle activity throughout a dynamic, asymmetric lifting motion. AB - This study examined the effects of trunk speed and exertion level on temporal aspects of trunk muscle activity patterns during dynamic, asymmetric lifting. Electromyographic (EMG) data from eight trunk muscles were collected along with trunk torque output, position, and velocity data during several repetitions of four speed/loading combination conditions. During analysis, each muscle's EMG record was reduced to three key events: a start, a peak, and an end point. For each subject, temporally ordered event lists were constructed for each test condition. Networks of events that consistently occurred regardless of loading or speed levels were constructed for each subject. Two event pairs occurred consistently for all subjects under all conditions, whereas some pairs occurred in association with specific speed or resistance levels. Temporal information related to muscle activity could be used in biomechanical models in order to predict changes in spinal loading during the course of workplace tasks. PMID- 1601434 TI - Coactivation of the trunk muscles during asymmetric loading of the torso. AB - Materials handling tasks in industry are rarely performed in the midsagittal plane. Often these tasks, labeled nonsagittally symmetric or asymmetric lifting tasks, can be expected to lead to an unequal distribution of forces between the left and right sides of the body. Because of the large number of muscles capable of resisting loads in the torso, researchers are forced to make simplifications when using biomechanical models to estimate mechanical loading of the spine during such tasks. Simplifications and assumptions regarding the coactivation of antagonistic muscles are frequently used because sufficient experimental data do not exist. The present study was designed to quantify coactivation of the trunk musculature in response to applied asymmetric loads. This load was varied in direction from an anterior midsagittal plane orientation to a posterior midsagittal plane orientation in 15-deg increments. The results showed little coactivation when the applied load directions were anterior and within 45 deg of the midsagittal orientation. When load directions were greater than 45 deg, coactivation was quantifiable in ipsilateral and posterior muscle groups. PMID- 1601435 TI - Multiple dipole modeling and localization from spatio-temporal MEG data. AB - An array of biomagnetometers may be used to measure the spatio-temporal neuromagnetic field or magnetoencephalogram (MEG) produced by neural activity in the brain. A popular model for the neural activity produced in response to a given sensory stimulus is a set of current dipoles, where each dipole represents the primary current associated with the combined activation of a large number of neurons located in a small volume of the brain. An important problem in the interpretation of MEG data from evoked response experiments is the localization of these neural current dipoles. We present here a linear algebraic framework for three common spatio-temporal dipole models: i) unconstrained dipoles, ii) dipoles with a fixed location, and iii) dipoles with a fixed orientation and location. In all cases, we assume that the location, orientation, and magnitude of the dipoles are unknown. With a common model, we show how the parameter estimation problem may be decomposed into the estimation of the time invariant parameters using nonlinear least-squares minimization, followed by linear estimation of the associated time varying parameters. A subspace formulation is presented and used to derive a suboptimal least-squares subspace scanning method. The resulting algorithm is a special case of the well-known MUltiple SIgnal Classification (MUSIC) method, in which the solution (multiple dipole locations) is found by scanning potential locations using a simple one dipole model. Principal components analysis (PCA) dipole fitting has also been used to individually fit single dipoles in a multiple dipole problem. Analysis is presented here to show why PCA dipole fitting will fail in general, whereas the subspace method presented here will generally succeed. Numerically efficient means of calculating the cost functions are presented, and problems of model order selection and missing moments are discussed. Results from a simulation and a somatosensory experiment are presented. PMID- 1601436 TI - Maximum-likelihood estimation of current-dipole parameters for data obtained using multichannel magnetometer. AB - A method is proposed to reduce the influence of external noise magnetic field on the accuracy of estimating current dipole parameters. It utilizes the spatial correlation of external noises, and is applied to data measured using a multichannel magnetometer. Computer simulation clearly demonstrates the effectiveness of the proposed method. PMID- 1601437 TI - Microwave radiometry in living tissue: what does it measure? AB - The sensitivity of microwave radiometry for detecting subcutaneous targets was studied both experimentally and theoretically. The radiometer used a dielectric loaded rectangular waveguide antenna in contact with a lossy dielectric medium. A cylindrical target with dielectric properties and/or temperature different from that of the surrounding medium was located beneath this surface. For most of the studies, the target and the surrounding medium were maintained at constant, but unequal, temperatures (i.e., heat conduction effects were insignificant). The received radiometric signal was calculated as the location and dielectric properties of the target were varied. Finally, the radiometer signal was calculated for the situation with the target maintained at constant temperature but with the surrounding medium modeled by the bioheat equation. Experimental studies were performed using a radiometer operating at 4.7 GHz. The target was a thin walled tube through which a temperature controlled liquid was circulated, located in a temperature controlled fluid tank. The results indicate that microwave radiometry (as used in this study) responds to the temperature averaged over the field pattern of the antenna with very strong weighting of regions near the surface. A simple quasi-static analysis provides a good indication of the sensitivity of the technique for detecting cylindrical targets whose dielectric properties are different from those of the surrounding medium. A simple estimate of thermal conduction around the target suggest that thermal effects greatly increase the apparent size of the target. PMID- 1601438 TI - Optimal power deposition with finite-sized, planar hyperthermia applicator arrays. AB - Improved hyperthermia applicator technology is allowing finer spatial power resolution within the heated tissue volume. Effective utilization of these planar applicator arrays requires an understanding of the interrelationships between the lateral dimensions of the tumor and the applicators, the power field produced by the applicators, the amount of surface cooling, the tumor tissue blood perfusion, and the normal tissue blood perfusion. These interrelationships are investigated using three-dimensional power patterns and temperature fields produced by optimizing the power amplitudes of the individual applicators located within an array of small, but finite, planar applicators. Five major conclusions are obtained. First, optimization works and is effective in determining optimal power fields. Second, for optimal treatments the lateral dimensions of a single superficial applicator need to extend beyond the tumor boundary. Third, surface cooling is needed to reduce the high normal tissue temperatures at shallow depths. Fourth, finer power resolution becomes more important as the tumor size decreases, but, little improvement in the temperature field is achieved beyond a 3 x 3 array configuration. Fifth, increasing the normal blood perfusion rate can decrease the temperature on the tumor boundary if direct power deposition on that boundary is unavailable. PMID- 1601439 TI - Microstrip-antenna design for hyperthermia treatment of superficial tumors. AB - Microstrip antennas have many different advantages over other RF/MW radiative applicators employed for superficial hyperthermia treatment. This is mainly due to their compact and body-conformable structure as well as to printed circuit board techniques, both of which allow a wide design flexibility for superficial tumor heating. Among the wide variety of radiator configurations, three microstrip antennas of increasing complexity with electromagnetic and heating characteristics potentially suitable as applicators for superficial hyperthermia have been designed, developed, and tested in different radiative conditions: a microstrip disk, a microstrip annular-slot, and a microstrip spiral. Electromagnetic design criteria are presented together with the determinations of the applicator return loss versus frequency and thermograms of the near-field heating pattern in muscle-like phantom. The results are in good agreement with theory and indicate that: i) the operating frequency is either single or multiple according to the applicator-mode, "resonant" or "traveling-wave," and can be chosen in the useful frequency range for hyperthermia (200-1000 MHz) according to the tumor cross-section and depth; ii) the heating pattern flexibility increases going from the simple geometry disk to the annular-slot and spiral applicators; iii) a distilled-water bolus is required; iv) the annular-slot applicator exhibits the highest efficiency, while the spiral applicator provides the best performance. PMID- 1601440 TI - Closed-loop class E transcutaneous power and data link for microimplants. AB - Magnetic transcutaneous coupling is frequently used for power and data transfer to implanted electronic devices. The proposed development of MicroImplants, small enough to be injected through a hypodermic needle suggest the need for a high efficiency magnetic transcutaneous link. This paper describes the use of a multifrequency transmitter coil driver based upon the Class E topology. The development of a "high-Q approximation" which simplifies the design procedure is presented. A closed-loop controller to compensate for transmitter and receiver variations, and a method of data modulation, using synchronous frequency shifting are described. The closed-loop Class E circuit shows great promise, especially for circuits with unusually low coefficients of coupling. Currents of several amperes, at radio frequencies, can easily and efficiently be obtained. PMID- 1601441 TI - Computerized transcutaneous control of a multichannel implantable urinary prosthesis. AB - In the present paper we describe a personal computer interface of a multichannel implantable urinary prosthesis. This system is composed of two main parts: the first one is internal and consists of an implant using a 4-microns CMOS gate array chip controlling a wide variety of waveforms via eight monopolar channels. The second, an external controller featuring a versatile software, a PCB card plugged in a portable microcomputer, and a radiofrequency-coupled technique. This device is used to transmit the power, the data and the synchronization clock to the implant by a simple binary signal modulating a 20 MHz carrier. We also report the features of implant encapsulation and electrode design and fabrication. In the experimental phase, we studied the effect of early electric stimulation of the bladder during the spinal shock phase in the dog. We present the operative techniques that enabled us to perform chronic electrostimulation of the sacral roots and discuss the results. PMID- 1601442 TI - Assessment of input-output properties and control of neuroprosthetic hand grasp. AB - Three tests have been developed to evaluate rapidly and quantitatively the input output properties and patient control of neuroprosthetic hand grasp. Each test utilizes a visual pursuit tracking task during which the subject controls the grasp force and grasp opening (position) of the hand. The first test characterizes the static input-output properties of the hand grasp, where the input is a slowly changing patient generated command signal and the outputs are grasp force and grasp opening. Nonlinearities and inappropriate slopes have been documented in these relationships, and in some instances the need for system returning has been indicated. For each subject larger grasp forces were produced when grasping larger objects, and for some subjects the shapes of the relationships also varied with object size. The second test quantifies the ability of the subject to control the hand grasp outputs while tracking steps and ramps. Neuroprosthesis users had rms errors two to three times larger when tracking steps versus ramps, and had rms errors four to five times larger than normals when tracking ramps. The third test provides an estimate of the frequency response of the hand grasp system dynamics, from input and output data collected during a random tracking task. Transfer functions were estimated by spectral analysis after removal of the static input-output nonlinearities measured in the first test. The dynamics had low-pass filter characteristics with 3 dB cutoff frequencies from 1.0 to 1.4 Hz. The tests developed in this study provide a rapid evaluation of both the system and the user. They provide information to 1) help interpret subject performance of functional tasks, 2) evaluate the efficacy of system features such as closed-loop control, and 3) screen the neuroprosthesis to indicate the need for retuning. PMID- 1601443 TI - The chronaxie for myocardium and motor nerve in the dog with chest-surface electrodes. AB - The chronaxie (i.e., the duration for a stimulating current having twice the rheobasic, or minimum, value) was determined for ventricular myocardium in 12 pentobarbital-anesthetized dogs. Current was applied transthoracically via chest surface electrodes located at the optimal axillary site for producing inspiration by stimulation of the phrenic nerve (electroventilation). In four dogs the chronaxie for motor-nerve was determined using electrodes at the same location. After using hand-held electrodes to identify the optimal stimulation site for electroventilation, 4.1 cm diameter electrodes were applied bilaterally to the optimal site on the thorax. In 12 dogs, the threshold current for producing ventricular ectopic beats was determined for single rectangular current pulses ranging from 0.1-10 ms in duration. From these data, strength-duration curves were determined and the average chronaxie for ventricular myocardium was found to be 1.82 ms. In four dogs the relationship between inspired volume and maximum stimulus intensity was determined using a 0.8 s burst of stimuli (60/s) with pulse durations ranging from 20-500 microseconds. From these data, strength duration curves for current were constructed and the average chronaxie for motor nerve was found to be 0.17 ms. The results of this study show that, because of the differing chronaxies, the current required to produce inspiration with short duration stimuli is much less than that required to evoke an ectopic heart beat. PMID- 1601444 TI - Optimal controller for intraaortic balloon pumping. AB - An optimal control algorithm was adapted to identify and track the optimal deflation time of the intraaortic balloon pump (IABP). Routines for handling physiologically imposed constraints were added to the algorithm which was implemented in a computer-controlled system. The system was designed to provide real time optimization for the clinical setting. The controller continuously maximizes a performance index while observing the constraints. The index is composed of clinically available hemodynamic variables which indicate changes in myocardial energy balance. Proper values for the algorithm parameters were determined and the system was tested in animal experiments. The results indicate that controlling deflation time relative to the R wave, which precedes the next ejection phase, reduces the time required for optimization when the heart rate varies. PMID- 1601445 TI - Factors influencing the biocompatibility of insertable silicon microshafts in cerebral cortex. AB - Insertable microelectrode arrays can be used to activate neurons or to sense neural signals for use in prosthetics. The relationship of the microelectrodes to the neurons is determined by random alignment and by biocompatibility. Issues that determine the biocompatibility of insertable microelectrode arrays were investigated. Arrays were implanted into the cortex of rabbit brain and fixed to the skull. Following six-month survival, neuron density as a function of distance from the shafts of the arrays was measured to assess destruction of neurons. Results from a limited number of tests indicated that there was minimal tissue response along the sides of the shafts when shafts were well sharpened, had sufficiently small tip angles, and were clean. Tissue was usually more reactive at the tips of the shafts. It was concluded that silicon microshafts of appropriate shaft and tip design were biocompatible along the sides of the shaft, but that relatively severe reactions could be anticipated at the tips. Recording or stimulation sites should be located away from the tips on the sides of the shafts for better coupling with individual neurons. Measurement of neuron density as a function of distance from the shafts was a sensitive and quantitative technique for assessing biocompatibility. Additional measures such as glial density as a function of distance from the shafts, and incidence of microhematoma formation were proposed. PMID- 1601447 TI - Adaptive cancellation technique in processing myoelectric activity of respiratory muscles. AB - Spectral analysis of myoelectric activity of the chest muscles is a promising diagnostic tool for respiratory diseases. Reduction of the corrupting cardiac activity from the recorded myoelectric activity of the chest muscles is essential because of the spectral overlap of both the signals. The adaptive noise cancellation technique was used to reduce the interfering cardiac activity from the recorded myoelectric activity. The adaptive noise canceller implemented in a transversal structure was found to successfully reduce the corrupting cardiac activity. This paper describes the cancellation of the corrupting cardiac activity from the recorded myoelectric activity using adaptive noise cancellation technique and the characteristic features of spectra of EMG signals. PMID- 1601446 TI - Confidence bounds on respiratory mechanical properties estimated from transfer versus input impedance in humans versus dogs. AB - Using parameters typical of a dog, we have shown that estimates for the parameters in the six-element model of Dubois et al. would be very unreliable if either input (Z(in)) or transfer (Ztr) data from only 2-32 Hz were fit. It has subsequently been shown that this model is not appropriate for human Z(in) from 2 320 Hz. However, several studies have continued to apply the model to human Ztr data from only 2-32 Hz. In this study a sensitivity analysis is used to determine whether and why the six-element model could be applicable to lower frequency (less than 64 Hz) Ztr data in humans, but not Z(in) data over any frequency range. We first predicted the joint parameter uncertainty bounds assuming a fit to either 2-32 Hz Z(in) or Ztr data created from literature based mean parameter values. Consistent with previous studies, we predicted that the estimates will be very unreliable if obtained from Z(in) data for humans or dogs, or from Ztr data from dogs. Surprisingly, however, the reliability of several parameter estimates from human Ztr data from only 2-32 Hz are reasonable. We next evaluated the variability in 2-64 Hz based Ztr parameter estimates by comparing experimental variability in two healthy human subjects (over 10 and 13 trials) to theoretical and Monte Carlo numerical predictions based on a single trial. Again, the Ztr parameters were reliable. A simulation study was used to describe the reasons for enhanced reliability when using human Ztr data. It is shown that this reliability is largely dependent on alveolar gas compressibility, Cg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601448 TI - A multimicroelectrode system composed of independent glass micropipettes with an eccentric tip structure for simultaneous intracellular recording. AB - A glass multimicroelectrode system for simultaneous intracellular recordings is described in which four pieces of micropipettes with rectangular cross section are arranged in a square compartment. Each tip position is shifted from the central axis of the electrode stem toward the crest line of its corner. Such micropipettes are mechanically bundled to one another so that the horizontal spacing among tips can be made shorter than the electrode diameter and components are independently penetrable. This paper offers techniques for fabricating such an eccentric micropipette. Finally, an example of simultaneous recordings of intracellular membrane potentials in the carp retina is demonstrated. This paper provides a technique which would allow researchers to record from three or four neurons simultaneously. PMID- 1601449 TI - The practice of empowerment and coercion by expert public health nurses. AB - This article describes the dialectic of public health nursing responsibility to empower families in self care as well as the nursing responsibility to evoke authority as needed to protect children from violence and neglect. Through qualitative study of expert home visiting public health nurses' anecdotes (N = 95), these apparently contradictory activities were discovered to co-exist in helping relationships. The synthesis of the apparent contradictions applies community rather than autonomy as the fundamental moral guide. PMID- 1601450 TI - The effects of gestational age and pregnancy planning status on obstetrical nurses' perceptions of giving emotional care to women experiencing miscarriage. AB - Obstetrical nurses (N = 292) were surveyed regarding the influence of gestational age and pregnancy planning on nurses' emotional care for women who had experienced miscarriage. Three measures of emotional care were used as the dependent variables: emotional seriousness, priority of care and emotional support. Both gestational age and whether the pregnancy was planned or unplanned had a significant effect on the nurses' perceptions of emotional seriousness and priority of care. Planning status was significant in the nurses' perception of emotional support. PMID- 1601451 TI - Eight homeless mothers' tales. AB - Families are the fastest growing subgroup of homeless people in the United States. In this qualitative study, interviews with eight homeless mothers were recorded and transcribed and themes were extracted telling of their struggles to overcome violation and find connection. PMID- 1601452 TI - Moving beyond: a generative philosophy of science. AB - Philosophies of science are perhaps the most covert yet significant forces influencing the direction of change within disciplines. Although the era of logical positivism has waned for many disciplines, newer philosophies may not be satisfactory, especially for the applied disciplines. This article describes an alternative philosophy of science with special significance for nursing. This philosophy was influenced by several of the major existing philosophies, but especially by the paradigmatic view espoused by Thomas Kuhn. The generative philosophy of science was named because of its focus on generating growth among the applied disciplines. Members of these disciplines study questions with social significance and human application. This article defines major concepts, describes relationships among concepts and discusses implications for the development of nursing science and the nursing discipline. PMID- 1601453 TI - The imposter phenomenon in the clinical nurse specialist role. AB - The imposter phenomenon describes individuals who at times feel as if they are imposters in their chosen profession. Individuals experiencing the phenomenon have a deep feeling that they are fooling everyone. The title of clinical nurse specialist (CNS) in itself may foster misinterpretations and false beliefs in oneself or others. The term "specialist" implies expertise in the five subroles of the CNS (educator, consultant, research, clinician and manager). Feelings of imposture within the CNS role can precipitate or exacerbate low self-esteem and lead to ineffective role implementation. The phenomenon must be recognized in the CNS and management strategies instituted. Management strategies include peer support, CNS mentoring and self-provided positive reinforcement. Further research is essential to document the existence of the phenomenon within the CNS role and the creation of effective management strategies to prevent or alleviate it. PMID- 1601454 TI - Family caring and caring in nursing. AB - Knowledge concerning family caring is developing within the caregiving literature while knowledge of caring is growing separately in the nursing literature. Both nurses (identified with caring) and family carers (identified with caregiving) experience a division of the affective and the instrumental dimensions of caring. Moreover, a historical perspective reveals that caring in nursing and family caring are faced with a common dilemma: caring in a society that undervalues caring. It is suggested that nurses, in the process of reconciling the dimensions of caring for their profession, consider family caring as a unified experience as well. PMID- 1601455 TI - Nurses who violate the Nurse Practice Act: transformation of professional identity. AB - The purpose of this interpretive research was to explore and describe the experiences of nurses who had been accused of violating the Nurse Practice Act. These nurses were investigated by the Florida Department of Professional Regulation (DPR); "probable cause" that a violation of the Nurse Practice Act occurred was found; the nurses participated in a hearing and were required to comply with the Board of Nursing's (BON) order. In-depth interviews with nurses, DPR and BON staff, participant observation at BON hearings and document analysis of BON files provided multiple slices of data. The grounded theory method was used for data analysis. These nurses experienced a transformation of professional identity. The transformation involved five phases - being confronted, assuming a stance, going through it, living the consequences and re-visioning. PMID- 1601456 TI - Simultaneous concept analysis of spiritual perspective, hope, acceptance and self transcendence. AB - This paper seeks to clarify four previously elusive concepts of concern to nurses: spiritual perspective, hope, acceptance and self-transcendence. Simultaneous concept analysis (SCA), a method developed by the authors, was used to generate a process model of antecedents, critical attributes and outcomes of all four concepts. This resulted in refined theoretical definitions for each concept. Interrelationships that became apparent among the concepts are discussed and implications of these interrelationships for theory and measurement are presented. PMID- 1601457 TI - Development of a measure of attitudes toward persons with AIDS. AB - This paper describes the development of a brief scale to measure attitudes toward persons with AIDS. Results from content validation, factor analysis, classical reliability estimation and generalizability analysis show the measure to have strong psychometric properties. PMID- 1601459 TI - Caring. PMID- 1601458 TI - Content and process in clinical decision-making by nurse practitioners. AB - Clinical decision-making is the process nurses use to gather information, evaluate it and make a judgment that results in the provision of patient care. This research sought to increase our understanding of clinical decision making by nurse practitioners. The sample consisted of 27 nurse practitioners; 6 OB/GYN nurse practitioners, 11 experienced family nurse practitioners and 10 inexperienced family nurse practitioners. All subjects cared for the same patient who was presented via computer and interactive video. Findings indicated that nurse practitioners use a process of clinical decision-making in which diagnostic hypotheses drive data acquisition. The OB/GYN nurse practitioners were more likely to develop lists of diagnostic hypotheses which reflected the patient's chief complaint, while both experienced and inexperienced family nurse practitioners were more likely to acquire subjective and objective data that did not appear to be hypothesis driven. PMID- 1601460 TI - DNR patients in intensive care. PMID- 1601461 TI - A thesis is born. PMID- 1601462 TI - Scientific misconduct. PMID- 1601463 TI - Linguistic methodologies in nursing research. PMID- 1601464 TI - Satisfying and stressful experiences of first-time federal grantees. PMID- 1601466 TI - On things strange... PMID- 1601465 TI - Decision-making patterns in adolescent mothers. PMID- 1601467 TI - Risk of hospitalization for chronic hemodialysis patients. AB - This study used primary data to analyze the incidence, causes and total days of hospitalization over a six-month period for a sample of chronic hemodialysis patients in one geographic area of the country. Patients were hospitalized most frequently for access-related and cardiovascular problems. Logistic regression analysis indicated that patients were more likely to be hospitalized if they had lower Karnofsky functional status scores, lower serum phosphate and protein levels, repeat access procedures, a negative hepatitis antigen, arthritis, psychiatric disorders, ischemic peripheral vascular disease or other cardiovascular conditions or were from larger households. Risk of hospitalization was not influenced by hemodialysis treatment characteristics. Recommendations for improved management of these high-cost patients were made, which could enhance quality of life and lower hospital-related costs. PMID- 1601468 TI - Spousal death, a threat to women's health: paid work as a "resistance resource". AB - This study examined the paid work role as a predictor of widows' health during conjugal bereavement. The sample of widows aged 55-75 bereaved for two years prior to the study (N = 157) was identified through recorded death certificates as the surviving spouses of deceased men. Work history and work attitude were statistically significant predictors of health during bereavement. PMID- 1601469 TI - Immune response to purified chick embryo cell culture rabies vaccine manufactured in India. AB - The immunogenic efficacy of the first batch of indigenous purified chick embryo cell culture grown (PCEC) rabies virus vaccine has been measured in ten subjects. All of them were immunologically naive to rabies virus, and were given 5 doses of the vaccine in the post-exposure regime of injections on days 0, 3, 7, 14 and 30. On day 7, four subjects had developed very low levels of rabies virus neutralizing antibody, as detected and measured in the suckling mouse neutralization test. On day 14, all subjects had protective levels of antibody, which were maintained or enhanced by day 30. With the limited data presented here, the immunogenic efficacy of this batch of vaccine appeared similar to that of a batch of imported PCEC vaccine investigated earlier. PMID- 1601470 TI - Metabolism of silicon as a probable pathogenicity factor for Mycobacterium & Nocardia spp. AB - The role of silicon (Si) in metabolism and growth of 22 strains of mycobacteria and 3 strains of nocardiae, which were mostly pathogenic, was studied on Kirchner's medium solidified with sodium metasilicate (KSM) and the C-free solidified metasilicate minimal medium (SMM) consisting of mineral salts only. On KSM, initial growth of mycobacteria appeared to be better, compared with that on Lowenstein-Jensen medium (LJM), although subsequent growth on the former was slower. On SMM lacking C, growth of mycobacteria and nocardiae could be achieved, only after repeated passages. These findings indicate that the mycobacteria and nocardiae are able to utilise Si at least to a limited extent, possibly as an alternative to C, with greater chances of survival. PMID- 1601471 TI - Plasmid mediated multidrug resistance in Salmonella typhi. AB - Between September 1989 and February 1991, strains of S. typhi showing multiple drug resistance were isolated from blood cultures of patients with typhoid fever. A total of 283 isolates were obtained over a period of 18 months. Forty four (11%) of these isolates were resistant to chloramphenicol, ampicillin, co trimoxazole and tetracycline, the first three being drugs currently used in treating typhoid fever. Forty of the 44 multi-resistant strains tested showed transfer of resistance 'en block' to recipient Escherichia coli K 12 (J62-2). All 44 multi-resistant strains were sensitive to ciprofloxacin and ofloxacin. Since the resistance is plasmid-mediated, the problem is likely to get aggravated. PMID- 1601472 TI - Multidrug resistant Salmonella typhi in Calicut, south India. AB - Eighty S. typhi strains isolated during the period of one year (July 1989 to June 1990) were tested for susceptibility to chloramphenicol, ampicillin, cotrimoxazole, gentamicin, kanamycin, cefazolin, furazolidone and ciprofloxacin. Determination of minimum inhibitory concentration (MIC) by tube dilution method showed that the multiply resistant S. typhi strains were resistant to chloramphenicol and ampicillin up to a concentration of 1000 micrograms/ml. MIC of sulphamethoxazole was found to be 800 micrograms/ml and trimethoprim 160 micrograms/ml. The presence of R plasmid was demonstrated by resistance transfer experiments using Esch. coli K12 (F-Lac+Nal-) as the recipient. On phage typing, most of the multiresistant S. typhi isolates were found to belong to phage type E1. PMID- 1601473 TI - Verocytopathic activity of Escherichia coli O157 & other 'O' serogroups isolated from patients of diarrhoea. AB - Twenty diarrhoeal isolates identified as Esch. coli O157 were screened for cytopathic activity on the continuous Vero cell line. Of these, seven strains (35%) showed cytopathic effect which was maximum on the 4th day after inoculation, with a maximum titre of 1 in 128. The total loss of cytopathic activity was observed in the positive filtrates subjected to a temperature of 100 degrees C for 15 min, while heating at 65 degrees C for 15 min, resulted in partial loss of this activity. All the verocytopathic strains were obtained from infants and children and were devoid of heat labile (LT) and heat stable (ST) toxins as well as enteroinvasive property. PMID- 1601474 TI - Detection of Chlamydia trachomatis antigen by enzyme immunoassay in patients with pelvic inflammatory disease. AB - In 27 out of the 60 women clinically suspected to have pelvic inflammatory disease (PID) studied, the C. trachomatis antigen titre was found to be higher than the cut-off value. Since the presence of C. trachomatis antigen was detected in 45 per cent of women, it is suggested that all the PID patients may be investigated by ELISA to confirm the role of C. trachomatis as the etiological agent. PMID- 1601475 TI - Incidence of hypoglycaemia in children with severe Plasmodium falciparum malaria around Rourkela, Orissa state. AB - To determine the incidence of hypoglycaemia in children suffering from severe falciparum malaria, 23 patients from Rourkela (Orissa), were investigated. Plasma glucose and immunoreactive insulin were estimated before and at hourly intervals during quinine infusion. No child had hypoglycaemia at the time of admission. Correlation between parasite count and prequinine plasma glucose was not significant. In the period of quinine infusion, 20 patients showed fall in plasma glucose during all the three hours (P less than 0.05, P less than 0.01, P less than 0.01 at the end of 1st, 2nd, and 3rd h respectively) but the decrease to hypoglycaemic level (plasma glucose less than or equal to 40 mg/dl) was observed in only one child. Concomitant increase in plasma insulin was noticed in 18 of these patients. Decrease in plasma glucose and increase in plasma insulin was found to correlate well (r-0.78, P less than 0.001). Hypoglycaemia was found to be an infrequent complication of severe falciparum malaria in children from the area studied. Though decrease in plasma glucose was observed after quinine infusion, it was less severe and did not reach the hypoglycaemic level. PMID- 1601477 TI - Sandfly fauna of domestic & para-domestic habitats in arid & semi-arid zones of Rajasthan. AB - Sandfly fauna of three districts of Rajasthan representing arid and semi-arid environments are described. A total of 2,042 sandflies belonging to two genera and seven species were collected. The arid district of Bikaner with irrigational development (by means of canal) showed considerably higher density of species Phlebotomus papatasi (16.5 PMH) as compared to Jodhpur district (1.0 PMH). The species encountered were Ph. papatasi, Ph. sergenti, Sergentomyia punjabensis, S. babu babu, S. clydei, S. bhagdadis and S. christophersi. PMID- 1601476 TI - Biochemical studies on mouse liver following Plasmodium berghei infection. AB - The lipid composition of mouse liver following infection with P. berghei was investigated. The liver lipid contents of infected animals were greatly increased mainly due to the accumulation of triacylglycerides. There was enhanced lipid concentration (85.29%). Significantly (23.7%) depleted liver cholesterol was also found in the mice. Similarly, phospholipid contents of liver were also decreased by 19.90 per cent. The liver from P. berghei infected mouse produced more lipid peroxide, as compared to control animals (314%). Significant depletion was also observed in carbohydrate, glycogen and glucose (79.1, 86.26 and 78.6% respectively) contents of liver at high parasitaemia. The lower contents of nucleic acid in the infected hosts observed in the study may be partly due to the absorption of nucleic acids by the parasites from the host cells. PMID- 1601478 TI - Transient nephrogenic diabetes insipidus in a neonate. PMID- 1601479 TI - Peripheral precocious puberty with hypertension. PMID- 1601480 TI - Hemolytic uremic syndrome: recent developments. PMID- 1601481 TI - Choledochal cyst in a neonate. PMID- 1601482 TI - Renal glycosuria in two siblings. PMID- 1601483 TI - Solitary thyroid nodule. PMID- 1601484 TI - Unusual complications in a multidrug resistant Salmonella typhi outbreak. PMID- 1601485 TI - Tuberculosis in children with reference to their immunization status: a hospital based study. PMID- 1601486 TI - Use of medicines in pediatric practice: tablets vs liquids. PMID- 1601487 TI - Agenesis of frontal bone. PMID- 1601488 TI - Fumigation of neonatal nursery: how effective in reducing the environmental pathogens? PMID- 1601489 TI - Complete covered anus in female neonates. PMID- 1601490 TI - Trace element research in pediatric practice. PMID- 1601491 TI - Epidemiological and clinical features of acute poliomyelitis children admitted in an urban hospital. AB - Six hundred and fourteen acute poliomyelitis children (57% boys) admitted to the Institute of Child Health, Madras, during January 1988 to September 1989 were studied. Diagnosis was based on clinical grounds. The age ranged from 2 months to 75 months. Residents of Madras city area were 31%, the rest being from neighbouring district (55%) and states (14%). Only 24% got protected water supply and 26% had access to safe disposal of excreta. Only a quarter (26.4%) had been immunized with 3 or more doses of oral polio vaccine. Intramuscular injection was given in 70% within one month of onset of paralysis. The commonest presentation was spinal form (80%) followed by spinobulbar (18%) and bulbar form (2%). Paralysis was severe in 72%, moderate in 6% and mild in 22%. Case fatality was 3.3%. The age at paralysis and clinical features in India have not changed over years. We conclude that the immunization programme should be effectively implemented to the maximum efficiency especially for the poor/illiterate community. Clinicians must be educated to avoid unwarranted intramuscular injections for any febrile illness. PMID- 1601492 TI - A survey of missed opportunity for immunization in Lucknow. AB - An exit interview of the women accompanying the children of 0-2 years visiting the three large urban hospitals and three randomly selected rural primary health centres of Lucknow district was undertaken to assess the magnitude of problem of missed opportunity for immunization at health facilities. The WHO suggested protocol for the study was followed. Observations reveal that in 59.1% children, the opportunity to vaccinate was missed. Only 3% children had a true contraindication for vaccination. Also 44.6% of women accompanying the children and in the reproductive age group could have been immunized against tetanus. A high level of acceptability of immunization in those with missed opportunity was noted. PMID- 1601493 TI - Impact of national immunization schedule on vaccine preventable diseases: a hospital based study. AB - An analysis of vaccine preventable diseases (VPD) in two block years, i.e., 1972 1975 and 1986-1989 showed an overall decline in morbidity and mortality. Improvement in morbidity was most noticeable in typhoid fever followed by polio and tetanus. However, in tuberculosis and measles with compilations, there was a significant increase in admission rates 3.8 vs 4.4% and 1.8 vs 2.2%, respectively. Mortality in vaccine preventable diseases except polio has declined significantly. PMID- 1601494 TI - BCG vaccination in malnourished child population. AB - The efficacy of BCG vaccination is still a subject of controversy. In the present study the protective role of BCG vaccination, the influence of nutritional status and justification for revaccination in children were investigated. Of the 504 preschool children suffering from tuberculosis who were registered for the study, 345 children did not receive BCG vaccine while the others had it during early infancy. Vaccinated children showed a significantly greater tendency to localise the tubercular lesions while most of the unvaccinated children suffered from progressive forms of the infection. Vaccination had similar effects even when there was associated malnutrition. Age did not seem to influence the severity of the disease in unvaccinated children while older children (greater than 3 yrs) had a greater tendency to localise the lesion in the vaccinated group. These data do not support the proposal of administering a booster dose of BCG to children who were vaccinated during early infancy. PMID- 1601495 TI - Clinical profile of measles--a prospective study of 150 hospital based children. AB - The clinical profile of 150 hospital based cases (6 months-7 yrs) of measles presenting between May 1986 to May 1987 was analyzed. Nearly a quarter (28%) were less than 1 yr; 60% belonged to 1-3 yrs age group, 8.6% were 3-5 yrs old and 2.6% were in the 5-7 yrs age group. The male:female ratio was 1.2:1. Nearly half (53.3%) were well nourished, 36.6% had Grades I-II PEM and 9.9% had Grades III-IV PEM. About half (47%) showed no complications; 53% had some complications of which 15% had more than one system involvement. Respiratory complications were seen in 50%, nutritional deterioration in 17.3%, gastrointestinal and neurological in 14.6% each and cardiac in 1.3%. The respiratory complications included pneumonia (16%), bronchitis (12.6%), activation of TB (10.66%), otitis (7.3%) and miliary tuberculosis (4%). CNS complications were encephalitis in 8%, meningitis in 3.3%, convulsions -2.6% and limb paresis in 0.6%. Children below 1 yr had a greater incidence of complications and multisystem involvement. Children between 3-5 yrs had respiratory and GI system involvement and children greater than 5 yrs showed respiratory system involvement only. No complications were seen in the well nourished group while early grades of PEM had mild complications. Severe degree of malnutrition had higher incidence and severity of complications. The need for large coverage of measles vaccine in our country especially amongst the malnourished group is obvious. PMID- 1601496 TI - Position of heart in relation to sternum and nipple line at various ages. AB - Frontal X-ray pictures of 210 healthy children from birth to twelve years of age with radio-opaque markers at sternal ends and both nipples were reviewed. The position of centre of cardiac silhouette was correlated with sternal areas and internipple line. The heart was found to descend with age, its centre lying beneath mid-sternum during first six months of life and beneath lower sternum after infancy (p less than 0.001). The position did not vary with age in relation to internipple line (p greater than 0.05). In 77.6% of all children, it was below the internipple line and in 22.4% above or at the internipple line. Because of the erratic relationship of cardiac centre with internipple line, the latter should not be considered a landmark for cardiac position. External cardiac massage should be applied in relation to sternum and at different locations according to the age. Sites for optimal compression have been suggested. No sexual dimorphism was observed. PMID- 1601497 TI - Measurement of ventricular size in term and preterm infants. AB - Real time ultrasonography was done in neonates to establish the norms for ventricular size and to see if there is a correlation between ventricle size and gestational age. A total of 153 normal infants admitted to our nursery after September, 1989 were taken up for the study. First ultrasound was performed within six days of birth. Sonography was done with 3.5 MHz transducer through anterior and lateral fontanelle. Results revealed that there is a significant difference in the mean value of falx to lateral wall of the cortex, ventricular index and ratio (VI/FC) of preterm and term infants. The ventricular size of small for gestational age infants is significantly different from appropriate gestational age infant of corresponding gestational ages. The percentile chart of VI for Indian infants is comparable to that of western infants. PMID- 1601498 TI - Multidrug resistant typhoid fever: study of an outbreak in Calcutta. AB - Of 103 cases of typhoid fever admitted to the Pediatric Wing of our hospital during the months of August 1989 to April 1990, 82.5% were resistant to chloramphenicol, ampicillin and co-trimoxozole. Nearly 87% children were in the age group of 3-10 years. Fever was present in all and splenomegaly in 90.2% cases. Urinary retention during the course of illness was present in 2 cases. The positivity rate of blood culture, bone marrow culture and Widal test was 83.7, 100 and 13.5%, respectively. Majority of the strains were of Phage 51-Type I. For the treatment of multidrug resistant cases gentamicin and furazolidine proved ineffective. Ciprofloxacin was tried in 85 cases and was found to be effective in all cases with no side effects. PMID- 1601499 TI - Nutritional beliefs amongst Anganwadi workers. AB - Knowledge about nutritive value of common foods, dietary beliefs during antenatal period, lactation, and during a few common diseases was assessed amongst 92 Anganwadi workers (AWW). All the workers were aware of the fact that during pregnancy, mothers require extra calories in order to meet the demand of fetus and 79.3% believed that simple multimix of cereals, pulses and oil prepared at home is much more nutritive than commercial weaning foods besides being cheaper. Nearly one fourth of the workers believed that both non-vegetarian foods as well as pulses should be avoided during the later half of pregnancy. Only 14.2% of AWW were not in favour of giving any food during episode of diarrhea while 27.2% believed that less food should be given to children suffering from pneumonia. It is suggested that there is need for updating the knowledge of AWW by continued in service health training. PMID- 1601500 TI - Strategies to sustain immunization coverage in India. PMID- 1601501 TI - Serological responses to hepatitis B virus infection in multi-transfused thalassemic children. AB - One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion. PMID- 1601502 TI - Congenital adrenal hyperplasia among peripubertal girls with hyperandrogenism. AB - Fifteen girls with severe hyperandrogenism were investigated by us during the last 6 years. Thirteen of these were cases of untreated congenital adrenal hyperplasia (CAH) and 2 were cases of tumoral (one sertoli leydig cell tumor of the ovary and one adrenal adenoma) hyperandrogenism. Here we present the clinical profile and laboratory data of those with congenital adrenal hyperplasia. All the girls had masculinization of genitalia (clitoromegaly alone 5, clitoromegaly with varying degree of posterior labial fusion 8). Eleven cases had hirsutism and 9 had short stature. Two patients underwent unilateral adrenelectomy with diagnosis of adrenal adenoma. Hormonal profile confirmed the diagnosis of CAH with 21 hydroxylase deficiency (elevated 17 OHP levels with exaggerated 17 OHP response to ACTH) in 12 cases and 3 beta hydroxy steroid dehydrogenase deficiency (elevated DHEAS and 17 pregnenelone levels and exaggerated DHEAS and 17 pregnenelone response to ACTH) in one case. PMID- 1601503 TI - Ketotifen. PMID- 1601504 TI - Practitioners' knowledge of prescribing costs of pediatric medications. PMID- 1601505 TI - Immunization awareness in mothers. PMID- 1601506 TI - Regression of precocious puberty in a child with hypothyroidism after thyroxine therapy. PMID- 1601507 TI - Congenital adrenal hyperplasia due to 11 beta-hydroxylase deficiency. PMID- 1601508 TI - Ethics in organ procurement in Turkey. PMID- 1601509 TI - Effect of subcutaneous administration of recombinant human erythropoietin on plasma protein C, protein S, and antithrombin III levels in patients on continuous ambulatory peritoneal dialysis. AB - The effect of subcutaneous administration of recombinant human erythropoietin (rHuEPO) on plasma natural coagulation inhibitors (protein C, protein S, and antithrombin III) was evaluated in 10 uremic patients on continuous ambulatory peritoneal dialysis (CAPD). These patients were commenced on a 16 week-course of twice weekly rHuEPO by the subcutaneous route. The hemoglobin increased significantly from 6.9 +/- 1.3 g/dl to 9.6 +/- 1.9 g/dl after subcutaneous rHuEPO treatment (p less than 0.01) at an average dose of 84 +/- 9 U/kg body wt/week. With rHuEPO therapy, a significant increase in platelet counts was observed, albeit within the normal range. A significant increase in the prothrombin time was demonstrated at 6 weeks after treatment and increased activated partial thromboplastin time was observed at 6 weeks and 16 weeks after rHuEPO administration although these measurements still remained in normal range. CAPD patients have comparable or even higher plasma levels of natural coagulation inhibitors compared with healthy controls supporting our previous findings that patients on CAPD have normal plasma levels due to an effective compensatory production despite peritoneal losses of these proteins with CAPD. No change in either the immunological or the functional activity of these natural coagulation inhibitors was demonstrated with rHuEPO therapy and clinical thrombosis was not observed during and after rHuEPO therapy. We conclude that there is no laboratory evidence of increased risk of thrombogenesis due to reduction of natural coagulation inhibitors with rHuEPO therapy. PMID- 1601510 TI - Hemostatic disturbances induced by two hollow-fiber hemodialysis membranes. AB - The effects on hemostasis of two high-flux membranes in hollow-fiber configuration, polyamide (PAM) and polyacrylonitrile (AN69), were analyzed in a cross-over study involving ten chronic hemodialyzed patients. Blood samples were obtained at arterial and venous sites of the extracorporeal circuit before dialysis and at 15, 30 and 180 min. Primary hemostasis: PAM induced an early significant drop in platelet counts, but at 180 min there was no longer any difference between membranes. Beta-thromboglobulin release by PAM was significantly higher at all time points. Coagulation: thrombin-antithrombin III complexes (TAT) and fibrinopeptide A increased significantly, the highest values being found with AN69. With both membranes the arterio-venous differences in TAT levels were negative throughout the sessions. Fibrinolysis: no significant differences were observed. In conclusion, both membranes induced hemostatic changes. Although these two hollow-fiber dialyzers look relatively similar, the changes observed were different, polyamide acting mainly on primary hemostasis and polyacrylonitrile on coagulation. PMID- 1601511 TI - Control of oral anticoagulation in patients using long-term internal jugular catheters for haemodialysis access. AB - Patients using long-term double-lumen silastic jugular catheters for haemodialysis access frequently require oral anticoagulants to maintain patency of the catheter. It may be difficult or impossible to obtain peripheral vein blood samples for PT measurements to regulate the oral anticoagulant dose. Our studies have shown that removal of 3 mls of blood from the catheter limb containing the heparin (to be discarded) followed by 10 mls as a heparin wash-out (to be returned to the patient) allows blood to be taken from the arterial limb of the catheter for PT measurement. The PT measurement obtained from the arterial limb after a 10 ml wash-out is nearly always identical with the PT measurement on blood obtained from a peripheral vein. If the simultaneously measured aPTT is normal the PT is predictably and consistently accurate. If the aPTT is raised due to traces of residual heparin then the PT may be inaccurate and should be repeated. This method is easy and reliable and can be recommended as an aid to regulation of the oral anticoagulant dose. PMID- 1601512 TI - Unusual case of anuria due to African bee stings. AB - We describe a case of multiple African bee stings in which the exceptionally high dose suggests a direct effect of hymenoptera venom on the renal tubules. The case does not follow the previously reported pattern of hypovolemic or anaphylactic shock, hemolysis and/or rhabdomyolysis, despite the potentially lethal amount of venom injected. PMID- 1601513 TI - Calcification modelling in artificial heart valves. AB - This study has examined a range of methods of studying the calcification process in bovine pericardial and polyurethane biomaterials. The calcification methods include static and dynamic, in vitro and in vivo tests. The analytical methods include measurement of depletion rates of calcium and phosphate from in vitro calcifying solutions, analysis of tissue contents of calcium, histological staining of tissue sections for calcium, X-ray elemental analysis, by scanning electron microscopy, of calcium and phosphorus distributions over valve leaflets calcified in vitro under dynamic conditions. Bovine pericardium, in all test settings, calcified to a much greater degree than polyurethane biomaterials. Polyurethane extracts calcified to a greater degree than bulk polyurethanes. The test protocol used allows progress through increasingly demanding calcification tests, with the possibility of eliminating unsuitable materials with tests of limited complexity and expense. PMID- 1601514 TI - Improved endothelialization of postfixation treated biological vascular grafts. AB - Preliminary in vitro and in vivo studies have shown that endothelialization is improved by a detoxifying postfixation treatment of glutaraldehyde (GA) fixed bovine pericardial patches and grafts. To test whether this is also true for GA tanned human vein (HUV) grafts, patches of commercially available HUV grafts (MHUV), postfixation treated HUV grafts (PTHUV) and GA fixed HUV granfts (GAHUV) were endothelialized in vitro. Eight pairs of MHUV and PTHUV grafts were implanted as femoropopliteal grafts in eight sheep. Endothelial cell adherence was significantly better on PTHUV (11910 +/- 4413 cells/cm2) than on MHUV (6545 +/- 2835 cells/mm2; p = 0.0007) and on GAHUV (3563 +/- 1638; p = 0.0001) one day after cell seeding. After eight days of culture significantly more cells spread on PTHUV material than on MHUV (p = 0.0002), but none of the cultures on GAHUV remained viable. Four PTHUV grafts occluded in the femoropopliteal position, mostly because of kinking, so that only in four pairs of grafts could the thrombus-free surface be compared by planimetry. Again PTHUV material was covered more by endothelial cells than was MHUV material. On PTHUV endothelial cells spread directly on the graft material while on MHUV these cells spread on a layer of fibrin and macrophages. Postfixation treatment of GA-fixed biological graft material by amino-acid solutions improves the biocompatibility of the material and enhances in vitro as well as spontaneous in vivo endothelialization. PMID- 1601515 TI - Near velocity field downstream prosthetic valves in aortic position. AB - Using a cardiovascular simulator to duplicate in vitro the flow conditions through valves in aortic position, bidimensional velocity maps very near the valve are reconstructed, from an ultrasonic 8 Mhz doppler system, in an elastic model of the ascending aortic arch. Three mechanical heart valves representative of the different types of commercial models (a tilting disc, a ball in cage and a two-leaflet valve) and a new bileaflet prototype were investigated. From examination of the velocity field, it is possible to define the main characteristics of the valve wake and to observe the development of negative velocities associated with regurgitant flows. From a comparison with tests in rigid tubes, the role played by the arch elasticity is analysed. PMID- 1601516 TI - Improved biocompatibility of heparin surface-coated ventricular assist devices. AB - Heparin surface coated ventricular assist devices (VADs) and cannulas were evaluated in comparison to uncoated VADs in 10 bovine experiments (body weight 77 +/- 6 kg). All systems were primed with cristalloid solution. No systemic heparin was given. Left ventricular assist was started with a blood flow of 4.2 +/- 0.4 l/min and maintained over 6 hours. Besides hemodynamic monitoring, blood samples were taken at regular intervals for blood gas, hematological, biochemical and coagulation studies. All animals in the study group (coated) were assisted for the scheduled 6 hours without device failure. In the control group, however, total occlusion occurred in 1 VAD after 1 hour of left ventricular assist whereas the other 4 VADs remained functional throughout the protocol. Mixed venous oxygens saturation was preassist 56 +/- 12% for coated versus 63 +/- 11% for uncoated and the final value at 60 minutes after weaning was 58 +/- 16% versus 59 +/- 5% (NS). Mean hematocrit dropped from a baseline value of 33 +/- 4% for coated versus 29 +/- 8% for uncoated to 29 +/- 7% versus 30 +/- 5% (NS) after 6 hours of assist. There was no significant difference between the baseline values (5.7 +/- 3.0 mumol/l for coated versus 4.6 +/- 3.1 mumol/l for uncoated) and the 6-hour values (3.8 +/- 3.7 mumol/l versus 7.6 +/- 6.4 mumol/l) for mean plasma hemoglobine. The normalized platelet levels dropped after 10 minutes of assist to 91 +/- 21% for coated versus 94 +/- 49% for uncoated (NS) and 89 +/- 29% versus 65 +/- 44 at 6 hours (NS).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601517 TI - The applicability of experimental experience with the total artificial heart to its clinical use. AB - Long-term experiments with the total artificial heart (TAH) are a source of valuable knowledge for later clinical application. Our observations result from 66 long-term experiments on calves and one goat ranging from 30 to 314 days, which have shown the main possible complications in the early period (one month) and later in the experiment. Problems until the second month of pumping concern the clinical pendant of the TAH as a bridge for transplantation, i.e. surgical problems, blood coagulation disorders, infection etc. Later problems are high venous pressure or arterial hypertension, infection with septic thromboembolization, mineralization of the driving diaphragm, etc., and are more closely comparable to the conditions of permanent clinical use of the TAH. Faultless surgery, device function and the regimen of pumping are essential factors in every long-term experiment, just as in clinical application. Infection is a threat throughout any experiment, as in clinical cases. The TNS-BRNO VII/clin/80 TAH has been implanted in six patients. PMID- 1601518 TI - Adsorption profile of commercially available adsorbents: an in vitro evaluation. AB - Adsorbents from four commercially available devices, Protein A-Sepharose (Immunosorba Protein A-62,5; Excorim KB, Lund Sweden), Tryptophan-PVA (Immusorba TR-350; Asahi Medical Co., Tokyo, Japan), Phenylalanine-PVA (Immusorba PH-350; Asahi Medical Co., Tokyo, Japan), and Dextran sulfate (Liposorber LA-15; Kanegafuchi Chemical Co. Ltd, Osaka, Japan) were tested under optimal in vitro conditions to determine their adsorption capability for several plasma constituents which are usually the target of plasma therapy. The parameters of interest were: double stranded DNA-antibodies (anti-dsDNA), antiglomerular basement membrane antibodies (anti-GBM), anti-acetylcholin receptor antibodies (AChRAb), circulating immune complexes (CIC), rheumatoid factor (RF), IgA, IgG, IgM, IgE, C3c, C4, LDL-cholesterol, total cholesterol, erythropoietin (EPO) and beta 2-microglobulin (beta 2M). The IgG auto antibodies, CIC and RF can be removed by Protein A-Sepharose, Try-PVA and Phe-PVA. IgG is best adsorbed by Protein A-Sepharose, while IgE can be removed efficiently by Try-PVA. Dextran sulfate is without doubt the best adsorbent for LDL-cholesterol. All four adsorbents bind also complement components C3c and C4. No significant adsorption was found for EPO and beta 2M. The four devices exhibit a quite different adsorption profile which can be used as a guide for the optimal selection of an adsorption column in clinical apheresis. PMID- 1601519 TI - Basement membrane collagen-IV synthesis in colorectal tumours. AB - Many studies suggest that increased proteolysis accounts for the epithelial basement membrane (EBM) breaks commonly seen in carcinomas. As failure to produce or maintain EBM may also be important, we chose to investigate synthesis of basement membrane collagen-IV in human colorectal carcinomas. First, to determine the cellular origin of EBM collagen-IV, species-specific antibodies were used to analyse caecal xenografts of 4 different human colorectal-carcinoma-derived cell lines. The results of this study suggest an exclusively stromal cell origin for EBM collagen-IV. Next, the distribution of periglandular myofibroblasts in carcinomas was examined, since in normal mucosa their location and ultrastructural features suggest that they play a role in EBM maintenance. They were generally abundant in normal mucosa and adenomas, but sparsely distributed in carcinomas, particularly at the invasive periphery where EBM collagen-IV immunostaining is most deficient. Finally, the in situ hybridization technique was used to define cell populations synthesizing collagen-IV. In normal mucosa, no collagen-IV mRNA was detected in any component, while in carcinomas, the mRNA was clearly detectable in vascular endothelial cells but not in any other cell type. Increased vascular collagen-IV production in carcinomas may be at least partly due to tumour-induced angiogenesis, since new blood-vessel formation requires the synthesis of new vascular basement membranes. PMID- 1601520 TI - DNA flow cytometry, nuclear morphometry, mitotic indices and steroid receptors as independent prognostic factors in female breast cancer. AB - Clinical features, 8 histological variables, 7 nuclear morphometric variables, 2 mitotic indices, oestrogen-receptor (ER) and progesterone-receptor content (PR), DNA ploidy and S-phase fraction (SPF) were entered in a Cox's model to assess their independent predictive value in 216 breast-cancer patients followed up for over 9 years. In the whole series, histological type (p = 0.007), volume corrected mitotic index (M/V index) (p = 0.01), axillary-lymph-node (pN) status (p = 0.024) and the year of treatment (p = 0.045) predicted independently the recurrence-free survival (RFS). In a sub-analysis including SPF (n = 148), the year of treatment (p = 0.003), tumour diameter (p = 0.004), SPF (p = 0.022) and nuclear pleomorphism (p = 0.056) independently predicted the RFS. In a Cox's analysis of the whole series, tumour diameter (p less than 0.001), pN status (p = 0.001), PR status (p = 0.002) and the year of treatment (p = 0.021) were independent predictors of survival. In a separate analysis including also SPF (n = 148), tumour diameter (p less than 0.001), SPF (p = 0.003), pN status (p = 0.008) and the year of treatment (p = 0.015) proved to be independent prognostic factors. The results show that tumour diameter, pN status, M/V-index, histological type, SPF and PR status comprise a sufficient combination of prognostic factors in female breast cancer. In pN patients, age and SDPE may be of additional prognostic significance. The prognostic scores combining the independent prognostic variables reflecting both the proliferative rate and metastatic potential of the tumours are accurate predictors of the RFS and overall survival. PMID- 1601521 TI - Expression of mRNA for cytokines in tumor-infiltrating mononuclear cells in ovarian adenocarcinoma and invasive breast cancer. AB - Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor--ovarian adenocarcinoma and invasive breast cancer--was examined by in situ hybridization with 35S-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense c-DNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF alpha), interferon gamma (IFN gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF alpha, IL2 or IFN gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF alpha, IFN gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL. PMID- 1601522 TI - High HTLV-I proviral DNA level associated with abnormal lymphocytes in peripheral blood from asymptomatic carriers. AB - The level of proviral DNA in peripheral blood mononuclear cells from a representative group of asymptomatic HTLV-I carriers in Miyazaki district, an HTLV-I endemic area in Japan, was determined by a single-cycle polymerase chain reaction method (PCR). Of 217 subjects, 26% had a high level of proviral DNA, 43% a medium level, 18% a low level, and 13% an undetectable level. In the high-DNA group, 60% had at least 0.6% abnormal lymphocytes on peripheral blood smears, significantly higher than in those with low DNA levels (19%). This association was present for men of all ages and for women under 55. Men were more than twice as likely to have abnormal lymphocytes as well as high levels of proviral DNA. These differences may reflect different host responses to the virus by sex or by the time or route of infection. This study supports the utility of PCR for molecular screening in epidemiologic studies of the natural history of HTLV-I, and may lead to the identification of those carriers who are at greatest risk of developing HTLV-I-induced malignancy. PMID- 1601523 TI - Unusual expression and localization of heat-shock proteins in human tumor cells. AB - It has been suggested that members of HSP families represent the surface target of immune responses leading to tumor rejection in mice. Here we report that tumor cells, compared with normal cells, constitutively expressed 2- to 10-fold higher levels of intracellular HSP90. Moreover, in the absence of environmental stress, 2 lines (out of 6) expressed the "inducible" HSP72, which was also detectable in fresh tumor cells. HSP72 expression was not regulated during the cell cycle, in contrast with what has been observed with normal cells. Both HSP90 and HSP72 proteins exhibited a heterogeneous pattern of intracellular distribution in most cells, HSP72 being confined mainly to the nuclear compartment. Finally, we could detect both HSP90 and, to a lesser extent, HSP72 (that are generally believed to be located intracellularly) at the surface of some tumor cell lines. We conclude that tumor cells differ from normal cells in their pattern of HSP expression; this might imply a role of HSPs in eliciting an immune response against cancer. PMID- 1601525 TI - Overexpression of a synthetic phosphotyrosine protein phosphatase gene inhibits normal and transformed cell growth. AB - We studied the level of the cytosolic phosphotyrosine protein phosphatase (PTPase) (originally termed low-M(r) acid phosphatase) in normal NIH/3T3 and in v erbB-transformed fibroblasts. The level of the enzyme, assayed by ELISA, was inversely related to cell proliferation, normally growing cells had less enzyme than their contact-inhibited counterparts and v-erbB transformants had less enzyme than normal NIH/3T3. In order to overexpress the enzyme and study its effects in normal and transformed cells, we transfected a synthetic gene coding for the PTPase in control NIH/3T3 and v-erbB transformants. The overexpressed enzyme was recognized by antibodies raised against the native enzyme and, in cells overexpressing the PTPase, we observed a marked dephosphorylation of tyrosyl residues of cellular proteins. Cell proliferation, in both normal and v erbB transformants overexpressing the PTPase, was measured. We observed that PTPase overexpression was accompanied by significantly reduced thymidine incorporation in both cell types, either serum-starved or serum-stimulated. The ability of transformed v-erbB cells to grow in soft agar was also markedly decreased by overexpression of the enzyme. Taken together, our results indicate that overexpression of PTPase might interfere with mitogenic signalling pathways in both normal and transformed cells, and propose a role for PTPase in the control of cell proliferation. PMID- 1601524 TI - Regulation of surface-differentiation molecules by epidermal growth factor, transforming growth factor alpha, and hydrocortisone in human mammary epithelial cells transformed by an activated c-Ha-ras proto-oncogene. AB - Spontaneously immortalized human mammary epithelial cells MCF-10A were transfected with an activated c-Ha-ras oncogene. Transfected cells (MCF-10T) acquire a malignant phenotype, as already reported. Studies of 125I-2' deoxyuridine incorporation in cultures given graded doses of hydrocortisone (HC), cholera toxin (CT), epidermal growth factor (EGF), and transforming growth factor alpha (TGF-alpha) showed that though MCF-10T had become almost independent on exogenous EGF and TGF-alpha, they continued to respond to the synergistic effect of HC and CT plus EGF. Both lines were phenotypically characterized with an immunoradiometric assay in live cells. Expression of MHC class-I molecules, human milk-fat-globule-I antigen, and EGF receptor was reduced in ras-transfected cells, although other differentiation markers were unchanged. Exogenous EGF down regulated the expression of functional EGF-R, selectively in transformed cells. TGF-alpha failed to modulate EGF-R. In contrast, HC strongly stimulated the expression of EGF-R while depressing MHC class-I molecules. Thus, it appears that in vivo HC may co-operate with TGF-alpha and EGF in promoting the growth of transformed mammary cells. This hormone might also favor the escape from immune surveillance by reducing the expression of surface differentiation markers. PMID- 1601526 TI - The growth rate of two transplantable murine tumors, 3LL lung carcinoma and B16F10 melanoma, is influenced by Hyal-1, a locus determining hyaluronidase levels and polymorphism. AB - The effect of 2 different levels of serum hyaluronidase on tumor development was studied by comparing the development of 2 transplantable tumors, the 3LL lung carcinoma and the B16F10 melanoma, in mice of the C57BL/6 and the congenic HW23 strains. The reasoning behind the study was that, in vitro, removal by hyaluronidase of the hyaluronan present in the extracellular matrix of tumor cells renders the latter more accessible to effector T cells. In the mouse, the levels and molecular forms of circulating hyaluronidase are under the influence of different alleles at the Hyal-1 locus on chromosome 9. C57BL/6 mice which have the Hyal-1b allele have only a 60,000-kDa form of hyaluronidase in the circulation, whereas the congenic HW23 strain has, on a C57BL/6 background, the BALB/c-derived Hyal-1a allele, characterized by the presence of the 60-, 120- and 140-kDa forms and of 3 times as much enzyme activity as the C57BL/6 strain. These 2 mouse strains that are genetically almost identical can therefore be used to compare the effect of different levels of circulating hyaluronidase on tumor development. Two different tumors were studied: the 3LL lung carcinoma and the B16F10 melanoma. After intrafootpad inoculation, both tumors developed more slowly in the congenic Hyal-1a HW23 strain, as measured by a slower rate of increase in local tumor size and by a prolonged survival time. These results are in favor of the hypothesis that the Hyal-1a allele, determining higher hyaluronidase levels, enhances resistance to tumor development. PMID- 1601527 TI - Quantitative study of the growth of experimental hepatic tumors in rats by using magnetic resonance imaging. AB - Precise estimation of the volume and growth rate of hepatic metastases would represent an important step forward not only in clinical oncology but also for the evaluation of experimental treatments in animal models. In the present study, an original method of volumetry of hepatic metastatic tumors in vivo has been tested in rats using magnetic resonance imaging (MRI). Three different hepatic tumor models mimicking liver metastases were established in syngeneic BDIX rats by injection of DHD/K12 rat colon cancer cells either directly under the liver capsule or via the portal system. The liver tumor volumes were estimated in vivo by using MR imaging of the liver and summing the individual tumor volumes in the sequential MR liver sections. The values of the tumor volumes measured by MRI were compared with those determined by a classical method of water displacement in vitro after killing the animals and excising the tumors. At 3 weeks after tumor implantation, liver tumors as small as 1 mm in diameter could be detected by MRI. The difference between the tumor volumes estimated by MRI in vivo and those measured by water displacement in vitro was 9% for single liver tumors and 16% for multiple liver tumors. Close correlation between the values of the tumor volumes measured by MRI and those determined by water displacement was observed in solitary liver tumors (r = 0.985, p less than 0.01) as well as in multiple liver tumors (r = 0.985, p less than 0.01), indicating the high accuracy of MRI volumetry for liver tumors. Estimation of the liver tumor volumes by MRI in the same animals at successive time intervals made it possible to construct tumor growth curves and to calculate tumor growth parameters. These data suggest that MRI volumetry represents an effective means of evaluating the efficacy of experimental treatments in small animals and may have potentially important applications in clinical patients. PMID- 1601528 TI - Striving for standards in bioequivalence assessment: a review. PMID- 1601529 TI - Bioequivalence studies: single vs multiple dose. AB - Bioequivalence of different preparations of the same drug substance has gained considerable importance over the last few years due to increasing generic substitution. The procedure that the manufacturer of the generic test preparation has to show bioequivalence with an appropriate reference preparation is scientifically accepted and laid down in international regulations. However, the necessity of single- vs multiple-dose bioequivalence studies has not been discussed in detail with the exception of the Dutch and US guidelines on sustained-release theophylline formulations, where multiple-dose studies are specifically required. This paper compares the conclusions drawn from single- and multiple-dose studies in the same subjects and recommends appropriate pharmacokinetic characteristics. PMID- 1601530 TI - A distribution-free procedure for the statistical analysis of bioequivalence studies. AB - In bioequivalence assessment, the consumer risk of erroneously accepting bioequivalence is of primary concern. In order to control the consumer risk, the decision problem is formulated with bioinequivalence as hypothesis and bioequivalence as alternative. In the parametric approach, a split into two one sided test problems and application of two-sample t-tests have been suggested. Rejection of both hypotheses at nominal alpha-level is equivalent to the inclusion of the classical (shortest) (1-2 alpha) 100%-confidence interval in the bioequivalence range. This paper demonstrates that the rejection of the two one sided hypotheses at nominal alpha-level by means of nonparametric Mann-Whitney Wilcoxon tests is equivalent to the inclusion of the corresponding distribution free (1-2 alpha) 100%-confidence interval in the bioequivalence range. This distribution-free (nonparametric) approach needs weaker model assumptions and hence presents an alternative to the parametric approach. PMID- 1601531 TI - Update on the statistical analysis of bioequivalence studies. AB - Statistical methods to assess bioequivalence of a test and a reference formulation are reviewed with emphasis on the distribution of bioequivalence characteristics and the consumer risk of erroneously accepting bioequivalence. Among the procedures not exceeding a nominal consumer risk of 5%, the one with an acceptably small producer risk of erroneously rejecting bioequivalence is selected. With the exception of tmax, the following strategy is recommended: a decision in favour of bioequivalence is made if the shortest 90%-confidence interval for the ratio of the expected medians is in the bioequivalence range for the chosen characteristics of rate and extent of absorption. If the assumption of a logarithmic normal distribution is not valid, the analogous nonparametric (distribution-free) 90%-confidence interval, which is also based on the two sample approach for the sequences reference/test and test/reference, is the procedure of choice. The issue of a modification of the bioequivalence range of 80-120% to other values for bioequivalence characteristics other than AUC (e.g. Cmax) is also addressed. Finally, a decision rule for tmax is presented. PMID- 1601532 TI - Sample size determination for bioequivalence assessment by means of confidence intervals. AB - The statistical analysis of bioequivalence assessment has been consolidated in recent years through the work of Schuirmann [1987], Westlake [1988] and Hauschke et al. [1990], and this has been reflected in the CPMP Note for Guidance on Bioavailability and Bioequivalence and in the joint recommendations of the APV (International Association for Pharmaceutical Technology) and ZL (Central Laboratories of German Pharmacists) during a recent workshop in support of EC Guidelines [Blume et al. 1990]. Since the decision procedure based on the inclusion of the shortest 90%-confidence interval in the bioequivalence range is the procedure of choice, and as this is equivalent to the two one-sided tests procedure, the sample size determination is based on the power of the latter. Following the approach of Phillips [1990] for the additive model, corresponding nomograms for the more relevant multiplicative model are given in this paper for various ratios of the expected means for test and reference and various coefficients of variation. PMID- 1601533 TI - Sample size determination: extended tables for the multiplicative model and bioequivalence ranges of 0.9 to 1.11 and 0.7 to 1.43. AB - For the two-period crossover design and a multiplicative model (logarithmic normal distribution) the decision procedure of choice is based on the inclusion of the shortest 90%-confidence interval for the ratio of expected medians for test and reference in the equivalence range. This inclusion rule is equivalent to the two one-sided tests procedure. Sample sizes based on the power of the latter have been given by Diletti et al. [1991] for an equivalence range of 0.8 to 1.25. Corresponding tables for the tighter equivalence range of 0.9 to 1.11 as well as for the wider range of 0.7 to 1.43 are given in this amendment. PMID- 1601534 TI - Lack of pharmacokinetic interaction as an equivalence problem. AB - The demonstration that concomitant administration of drug B does not affect the pharmacokinetics of drug A can be adequately handled as an equivalence problem. Administration of drug A alone serves as reference and simultaneous administration of drugs A and B as test situation. The range of clinically acceptable variation in the pharmacokinetic characteristics of drug A defines the equivalence range. This will usually correspond to the bioequivalence range accepted for the comparison of different formulations of drug A. Equivalence, i.e. lack of pharmacokinetic interaction, is concluded if the 90%-confidence interval for the ratio (difference) of the expected medians for test and reference is entirely within the equivalence range. This decision procedure ensures that the consumer risk of incorrectly concluding "lack of interaction" is limited to 5%. Moreover, the producer risk of incorrectly concluding "interaction" can be controlled by appropriate sample sizes. PMID- 1601535 TI - Presentation of results from bioequivalence studies. AB - Based on general guidelines and requirements for the design and analysis of bioequivalence studies, specific recommendations are made for the presentation of results, both in tabular and graphical form. This is done by means of two examples, one of a single-dose study and one of a multiple-dose study. The recommendations in this paper are twofold. Firstly, a complete and rather detailed presentation of results is given, which practically corresponds to the standard of research reports. Secondly, a subset of this is suggested for publication. It gives the essential results for bioequivalence assessment in a standardized form. From an editorial point of view, it would be highly appreciated if the papers submitted for publication were always accompanied by a complete presentation including the individual concentration/time data and the various steps of calculation. This would speed up peer review and ultimately improve and harmonize the standard of bioequivalence publications. PMID- 1601536 TI - Partner support, psychological treatment, and nicotine gum in smoking treatment: an incremental study. AB - Smokers (N = 99) were randomly assigned to one of three conditions: nicotine gum (NG), nicotine gum plus psychological treatment (NG-PT), and nicotine gum plus psychological treatment and partner support (NG-PT-PS). Data were collected at Weeks 0, 4, 12, 26, and 52 from study start. Contrary to expectations, NG-PT-PS and NG-PT failed to increase abstinence rates. Subjects who were closer to their support partners had significantly lower abstinence rates with NG-PT-PS than with the other conditions, although not significantly at Weeks 26 and 52. Treatments without partner participation (NG-PT and NG) were significantly more effective for subjects who had an extremely close support partner outside the treatment setting than for those who did not at all weeks. The role of social support in smoking treatment is discussed. PMID- 1601537 TI - Occupational role and perceptions of substance misuse in Australia. AB - This study examined ways in which people from different occupational backgrounds in South Australia perceived issues relevant to the misuse of substances. Questionnaires were completed by representatives from eight occupational groups, namely, Doctors, Nurses, Ambulance Officers, Social Workers, Youth Workers, Teachers, the Police, and Probation and Parole Officers (in total, N = 276). Significant differences were found between occupational groups in their judgments of the relative incidence of substance misuse in the community, the comparative harmfulness of alcohol and marijuana, the attribution of alcohol misuse to personal inadequacy, and the efficacy of treatment of alcohol misuse. PMID- 1601538 TI - Academic stream and tobacco, alcohol, and cannabis use among Ontario high school students. AB - This paper examines the relationship between academic stream and cigarette, alcohol, and cannabis use among 2,543 high school students as part of the Ontario Student Drug Survey (1987). Students in basic and general academic streams were found to have significantly higher levels of cigarette, alcohol, and cannabis use compared to advanced level students. The effects of academic stream remain significant (except for alcohol use) when gender, grade average, drug education lessons, and pressure to use these substances are included in multiple regression analysis. The findings indicate that the process of academic streaming needs to be further examined as a possible precipitating factor in drug use. PMID- 1601539 TI - Preventing fetal alcohol exposure: a cognitive behavioral approach. AB - Fetal alcohol exposure is a serious social and public health problem. However, most prevention programs in this area are solely informational. Important gaps in both understanding processes which underlie alcohol consumption during pregnancy and in the design of interventions to prevent fetal alcohol exposure are discussed. We argue that an important group missed by current interventions are women for whom abstinence is difficult, but who are not physically addicted. Cognitive behavioral interventions are proposed as appropriate for this target group. Recommendations for future directions in the area of fetal alcohol exposure are discussed. PMID- 1601540 TI - Behavioral relapse prevention strategies in smoking cessation. AB - The study deals with the efficiency of various relapse prevention strategies in smoking cessation therapy. It is designed to examine the efficiency of cognitive and behavioral relapse prevention strategies in conjunction with transdermal nicotine substitution and booster sessions. The results show that application of the relapse prevention strategies in this study provided no significant increase in the long-term effectiveness of smoking cessation therapy. The abstinence rates of the five therapy groups, which were roughly equal on completion of the therapy, showed a more marked decrease in all test groups than in the control group in the 6- and 12-month follow-up. PMID- 1601541 TI - Private insurance reform in the 1990s: can it solve the health care crisis? AB - A number of health insurance reform proposals have surfaced at the state governmental level in the United States. These include Medicaid expansion for the below-poverty or near-poverty uninsured, state subsidy to individuals and/or businesses for the purchases of health insurance, risk pools for the medically uninsurable, insurance industry-initiated reforms within the small group market, the promotion of "stripped down" insurance plans that reduce premium cost, and state mandating of employer-sponsored health insurance for the employed uninsured. All of these insurance reform proposals have serious limitations: (1) they fail to address the inequities of the underwriting principle by which older and sicker people pay more for health insurance than the young and healthy population; (2) they extend the illogical linkage of employment and health insurance; and (3) they do not slow the rate of health cost inflation nor do they contain a mechanism to finance broader health coverage through savings within the health sector. An alternative to insurance reform is the establishment of a social insurance program that brings the entire population into a single risk pool. PMID- 1601542 TI - International comparisons of physicians' salaries. AB - Data from recent international publications are used to analyze physician incomes across countries. U.S. incomes are the highest among 14 countries, even after adjusting for the average standard of living within each country. PMID- 1601543 TI - The politics of hunger: when science and ideology clash. AB - In recent years the WIC program, a federal nutrition program for poor mothers and babies, has become a major playing field for ideological forces hoping to shape public opinion and Congressional action on matters of domestic social policy. WIC's highly positive benefits have been distorted, research results from its scientific evaluation altered by high-level federal officials, and its public support undermined by an academic spokesman with ties to the White House and a stated desire to kill the program. While strong bipartisan support on Capitol Hill makes it likely that WIC will survive and even grow, distortion of its record provides insight into how ideological forces contaminate the well of reasoned discourse for their preconceived ends. PMID- 1601544 TI - Double exposure: the combined impact of the home and work environments on psychosomatic strain in Swedish women and men. AB - This study investigates the relative distribution of home responsibilities and psychosocial work environment characteristics and their associations with psychosomatic strain in a random sample of the female and male working population of Sweden (N = 12,772). Occupational variables investigated were psychological and physical demands, job control, social support, and job hazards. Home characteristics included measures of household work, number and age of children, and child care resources. A sex-pooled logistic regression analysis was performed to detect sex differences in the effects of the variables upon strain. Gender was no longer associated with psychosomatic strain after adjusting for work and home characteristics and their interactions, and while there were some similarities between the sexes with respect to the main effects of the home and work characteristics, in 52 of 60 combined effect comparisons women had a greater combined odds ratio for strain than men. PMID- 1601545 TI - Unemployment and mental well-being: elaboration of the relationship. AB - The relationship between unemployment and mental well-being was studied in 703 Finnish women and men who were originally employed in industry (manufacturing). A population survey with a follow-up measurement was carried out in 1983 and 1984. Mental well-being was measured by a 12-item version of the General Health Questionnaire. The association between unemployment and mental ill-health proved to be a strong one. Cross-sectional analyses and analyses on the improvement of mental well-being were made. The impact of employment status on mental ill health, as well as its improvement, was controlled for by means of logistic regression analysis (GLIM). Several variables included in the design did not alter the main result, apart from the fact that the impact of unemployment was stronger among men than among women. The impact of unemployment proved to be independent and direct. The author compares these results with other studies that have used a similar approach, and discusses the significance of paid work in developed capitalist societies in an understanding of the adverse impacts of unemployment. PMID- 1601546 TI - Neonatal mortality and the economy revisited. AB - The association between economic contraction and neonatal mortality previously reported in this Journal is retested using methods and data that respond to criticisms of aggregate time-series work. Results suggest that the risk of neonatal mortality among birth cohorts of black males in the Los Angeles County and Orange County metropolitan areas is increased by unexpectedly low levels of employment in the second trimester. The argument is made that the strength of the effect is probably not sufficient to make the case for stimulating regional economies more compelling. PMID- 1601547 TI - Community participation in Quebec's health system: a strategy to curtail community empowerment? AB - Since the beginning of the 1970s, the province of Quebec has undergone a major reform of its health and social services system. Following this reform, the state has become a major protagonist, and the participation of the population is a built-in element in the system, guaranteed by law. Now, about 20 years later, there is a major effort to reorganize health services, in the wake of a "dewelfarization" mood that has reached Canada and Quebec. This article reviews the successes and pitfalls of public participation in Quebec's health system, presents the way in which participation is dealt with in current reform proposals, and draws lessons for people in many countries who have recently been encouraged to jump onto the bandwagon of participation as a strategy to promote the health of populations. PMID- 1601548 TI - Community organizing among the elderly poor in the United States: a case study. AB - This case study demonstrates the role of community organizing as a vehicle for enhancing individual and community-level empowerment. Building on social support theory, Freire's "education for critical consciousness," and the principles and strategies of community organization practice, the 12-year-old Tenderloin Senior Organizing Project reflects the World Health Organization definition of health promotion as a means of helping individuals and communities to take increasing control over the factors influencing their health. Through the Project, low income elders have successfully identified and addressed shared problems in such areas as crime and safety, undernutrition, and tenants rights. They further have developed ongoing tenants' associations and other community-based organizations that have provided continuity over time and contributed to the development of a "competent community." Problems in areas such as funding, evaluation, and volunteer burnout are discussed, as are the potentials for project replication in other settings. PMID- 1601549 TI - Local advocacy for the medically indigent: strategies and accomplishments in one county. AB - Access to health care for the medically indigent has emerged as a major policy issue throughout the United States. Because no national health program assures entitlement to basic services, practitioners and patients must cope with barriers to access on the local level. The authors report several separate but integrated strategies that a community-based coalition has used to achieve improvements in indigent care within a single county. Research strategies have involved short term investigations of barriers to needed services, so that local awareness of the problem would increase rapidly. Political strategies have attempted to improve the county government's administrative procedures and financial support of services for the poor, to modify the practices of local health care institutions, and to influence statewide and national policies affecting local conditions. Legal strategies have involved the participation of attorneys who represent clients unable to receive care and who could initiate litigation as appropriate. Each of these strategies contains weaknesses as well as strengths. Although such advocacy efforts do not achieve a coherent system guaranteeing access, they can substantially improve the availability of local services. PMID- 1601550 TI - The Free Trade Agreement and the Mexican health sector. AB - This article presents a discussion of the probable implications for the Mexican health sector of the Free Trade Agreement (FTA) between the United States, Canada, and Mexico. The authors argue that the FTA should be seen as part of neoliberal policies adopted by the Mexican government in 1983 that are based on large-scale privatization and deregulation of labor relations. In this general context the health sector, which traditionally has been dominated by public institutions, is undergoing a deep restructuring. The main trends are the decapitalization of the public sector and a selective process of privatization that tends to constitute the private health sector in a field of capital accumulation. The FTA is likely to force a change in Mexican health legislation, which includes health services in the public social security system and recognizes the right to health, and to accelerate selective privatization. The U.S. insurance industry and hospital corporations are interested in promoting these changes in order to gain access to the Mexican market, estimated at 20 to 25 million persons. This would lead to further deterioration of the public institutions, increasing inequalities in health and strengthening the private sector. The historical trend toward the integration of a National Health Service in Mexico would be interrupted in favor of formation of a dual private-public system. PMID- 1601551 TI - Viewing primary mental health care at a time of social transition in South Africa. AB - As South Africa shifts from a social structure based on the principles of apartheid to a democratic society, social policies must be developed that are consonant with the ideals of the "new" society. These must, however, take into account the current realities of the South African context. This article suggests that the application of the principles of primary mental health care is the approach most likely to meet mental health needs in the future South Africa, but that difficulties are likely to arise in the transition to this approach. These difficulties must be identified and dealt with. The authors discuss the problems in providing competent curative care to all and in shifting emphasis to prevention and promotion in mental health care. The discussion covers both practical and political complications. The authors conclude that though the process to primary mental health care will be a long one, the problems are unlikely to be insurmountable. PMID- 1601552 TI - From chronic emergency to development: an analysis of the health of the urban poor in Luanda, Angola. AB - There is a dearth of published literature on health care systems in Angola. Like many sub-Saharan African countries, Angola is experiencing rapid urbanization. The authors provide an analysis of the health status, environmental health conditions, and health-related behavior of the urban poor in Luanda, Angola. Although data are patchy and rarely disaggregated to reveal severe conditions in the shanty towns, a grave picture emerges. An average infant mortality rate of 104/1,000, with malaria and intestinal infections the main causes of death in children under 1 year old, reflects the poor environmental conditions, which are worsening as urbanization continues at a rapid rate. Use of health services is limited; for example, 50 percent of women give birth at home, mainly unassisted, and only 28 percent of children are covered by measles immunization (as validated by card). A discussion of existing health strategies, programs, and their constraints is set in the context of the future possibilities of the ending of the 15-year war and the introduction of structural adjustment policies. PMID- 1601553 TI - Violence and health: preliminary elements for thought and action. AB - Violence is one of the most serious problems that society, and the public health sector in particular, has to deal with today. This article begins with a discussion of the concept of violence itself, bringing out its historical and cultural dimensions and emphasizing its essential relationship to the exercise of force in the interest of power under conditions of inequality. Violence must be seen as a process that includes its origins, the conditions that allow it to happen, its different forms of expression, and its individual and collective consequences. The violence-health relationship is seen as having different levels: violence threatens or denies not only health but the entire vital human process. The author analyzes the different forms of violence: violence that impairs health (torture, disappearances, rape, child abuse, elderly abuse) and violence that kills (suicide, homicide, war). Recent data show that the problem is on the increase and pervades everyday life. The author then examines the mechanisms by which violence impinges on health care institutions, especially the health services, training institutions, and agencies responsible for orienting and financing the sector. Finally, the health sector is revealed as not only a victim or patient of violence, but, unfortunately, sometimes an agent of violence, which means that changes are needed in approaches, attitudes, and behavior. PMID- 1601554 TI - Plasma hormones and physical exercise. AB - The analysis of published data allowed us to establish main traits of blood hormone responses to exercises: There are stable changes in hormone levels that are common to all persons, as well as changes which are characterized by a polyphasic pattern and exhibiting inter-individual variability. By the response rate it is possible to discriminate fast responses, responses of a modest rate and delayed responses. Accordingly, mechanisms for a rapid and for a delayed activation exist. The changes mediated through the mechanism for a rapid activation depend on the intensity of exercise, revealing the threshold intensity for endocrine response. When a certain amount of exercise is done, the hormonal responses are triggered despite the under-threshold intensity of exercise. Consequently, a threshold duration of exercise also exists. Through training the threshold intensity of exercise increases and the functional capacities of the endocrine systems augment. The former results in the disappearance of hormonal responses during exercise intensity which was previously above the threshold. The latter makes it possible to achieve especially pronounced and long-lasting hormonal changes during extreme exercises. Emotional states as well as environmental conditions, and carbohydrate supply modulate the hormonal changes in exercise. PMID- 1601555 TI - Plasma lipid levels in active and sedentary premenopausal females. AB - Cross-sectional data on 19 long-distance runners (LD), 17 aerobic dancers (AD), 19 recreational joggers (RJ), and 15 inactive controls (IC) were examined for cardiovascular endurance and determination of plasma lipoproteins. Subjects included premenopausal eumenorrheic females who were non-smokers and presently not using oral contraceptives. Results indicated that all groups were similar in age, height and weight. Only the AD group had a significantly lower percent body fat (p less than .001) than the other groups. The LD, AD and RJ groups had a significantly higher VO2max than the IC group (p less than .05), and the LD and AD groups had a significantly higher VO2max than the RJ group (p less than .05). Analysis of a one-day food log indicated that the only difference in diet among the groups was a significantly lower intake of total and monounsaturated fat in the AD group (p less than .05) and a significantly lower intake of carbohydrates in the IC group than the AD group (p less than .05). Analysis of plasma lipids revealed no significant differences in any lipid variables among the groups. These findings indicate that healthy premenopausal eumenorrheic females with similar physical characteristics also have similar plasma lipid profiles regardless of their physical activity level. PMID- 1601556 TI - Reliability of the serial sampling technique for determination of gastric emptying. AB - The purpose of this study was to determine if gastric emptying data obtained in one trial (using the intubation and aspiration method) is representative of that obtained in subsequent trials or on repeated days. Nine healthy adults consumed a volume of water (5.5 ml/kg body weight) which contained a nonabsorbable marker. Following a fifteen-minute rest period, the stomach contents were aspirated using a 50 ml syringe. This procedure was repeated three additional times on the same day with a fifteen minute interval separating each trial. On two other days the identical procedures were performed. A significant daily variation was found for residue volume, gastric secretion, and percent of original drink emptied. However, no significant difference between trials within a day was found for the residue volume, gastric secretion, and percent of original drink emptied. Generalizability coefficients, which are "reliability-like" coefficients, were also calculated. These coefficients indicate that a combination of at least 2 days with at least 2 trials/day should be used in order to obtain reliable gastric emptying data. PMID- 1601557 TI - Relationships between cardiac dimensions, anthropometric characteristics and maximal aerobic power (VO2max) in young men. AB - Echocardiographic dimensions, anthropometric data and maximal oxygen uptake (VO2max) were studied in 26 healthy sedentary male controls (mean age, 22.0 yrs) and 15 male endurance athletes (mean age, 20.3 yrs). Athletes displayed significantly greater mean values for left ventricular internal dimension at end diastole (LVIDd), end-diastolic volume (LVEDV) and left ventricular mass (LVM). Statistically significant positive correlations were observed within the sedentary control group between left ventricular end-diastolic dimensions (LVIDd, mm and/or LVEDV, cm3) and body height (cm), body weight (kg), chest circumference (cm) and body surface area (m2). Left ventricular mass (LVM, g) correlated significantly with lean body mass (kg). Ectomorphic somatotype rating (Ecto) correlated negatively with LVEDV and LVM. Finally, VO2max (l/min) correlated significantly with LVIDd, LVEDV and LVM. Multiple linear regression analysis indicated that the degree of endomorphy (Endo), LVIDd (mm/m2) and chest circumference accounted for 89% of the variance in VO2max (ml/kg/min) within the athlete group. Endo, Ecto and LVIDd (mm/m2) accounted for 86% of the variance in VO2max (ml/kg/min) in the control group. This study supports the hypothesis that maximal aerobic power can be predicted from cardiac and anthropometric measurements. PMID- 1601558 TI - Effects of exercise training on insulin response to intravenous glucose in pubertal rats. AB - This study was undertaken to evaluate the effects of exercise training on glucose tolerance and glucose-stimulated insulin response (GSIR) in 55- and 90-day-old peripubertal female rats. Intravenous glucose tolerance tests (0.5 g/kg) were done in: 1) 90-day-old rats exercised in swimming sessions for either 5 or 10 weeks and evaluated 48 h after the last exercise bout; 2) 55-day-old rats exercised for 5 weeks and evaluated either 24 h or 48 h after the last exercise bout and; 3) unexercised 55- and 90-day-old rats. The total area under the GSIR curve was suppressed in 55- and 90-day-old rats exercised since the age of 21 days. However, this decrease was observed 48 and only 24 h after the last exercise bout in the 90- and 55-day-old rats respectively. Exercise did not affect the GSIR curve for the 90-day-old rats subjected to 5 weeks of exercise training (started at 55 days of age) when evaluated 48 h after the last exercise bout. Nor did one single bout of swimming exercise (2 h) in the last 24 h affect the GSIR in unexercised 55-day-old rats. These results suggest that the shorter duration of the residual effects of exercise in the younger rats (55 days) was related to the shorter length of the training programme. Body weight was not significantly reduced with exercise in 55-day-old rats, whereas the same amount of exercise in 90-day-old rats caused body weight reduction of approximately 35 g (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601559 TI - Decreased nocturnal catecholamine excretion: parameter for an overtraining syndrome in athletes? AB - The effectiveness of high performance training should be examined at short intervals in order to recognize overtraining promptly. Field or laboratory tests can usually not be performed with such frequency. Easy-to-measure biological, training-relevant parameters are being sought to use in their place. Since the importance of the sympathetic nervous system for adaptation of stress and the relationship between physical training and the activity of the sympathetic nervous system are well accepted, and since an impairment of the sympathetic nervous system is assumed in an overtraining syndrome, we examined the relevance of nocturnal "basal" urinary excretion of free catecholamines with respect to its practical application: 1. during a pilot study (training of road and track cyclists before the 1988 Olympic Games in Seoul), 2. through a 4-week prospective, experimental study in 1989 and 1990 (middle- and long-distance runners), 3. during the competitive season and winter break of a soccer team between August 1990 and April 1991. The following hypothesis was made: An overtraining or exhaustion syndrome in athletes may usually be accompanied by at least a 50% decrease in basal dopamine, noradrenaline and adrenaline excretion. When training is effective or the athletes are not exhausted, the decrease of the excretion rate--with the exception of dopamine--is more likely to be lower (noradrenaline, adrenaline). Generalization of these results requires further expansion of the experimental basis. PMID- 1601560 TI - Maximal and functional aerobic capacity as assessed by two graduated field methods in comparison to laboratory exercise testing in moderately trained subjects. AB - This study was undertaken to determine which of the two commonly used field tests, the 20-meter shuttle run test (20-MST) or the University of Montreal track test (UM-TT), provides the most accurate assessment of maximal and functional aerobic capacity in moderately trained athletes. Eleven male subjects aged from 18 to 30 years were studied in triple incremental and continuous running tests carried out until exhaustion both in laboratory and field conditions. They underwent a laboratory treadmill test and completed the outdoor 20-MST and UM-TT. During the three randomly assigned tests, maximal velocity (Vmax), maximal oxygen uptake (VO2max), maximal heart rate (HRmax), and post-exercise peak blood lactate (P[La]) measurements were made. The results indicate a significant difference in the mean Vmax (F = 9.26, p less than 0.001). Vmax determined by the 20-MST revealed a lower value than by treadmill (16.3%) and the UM-TT (19.3%). In contrast, there was no difference with regard to VO2max (F = 2.95, p = 0.06), HRmax (F = 2.72, p = 0.08), and P[La] (F = 2.79, p = 0.07). These results confirm that the UM-TT is a valid field test of maximal and functional aerobic capacity in moderately trained subjects and suggest that it can be additionally used for exercise prescription. PMID- 1601561 TI - Normality, variability and predictability of work, power and torque acceleration energy with respect to peak torque in isokinetic muscle testing. AB - This study evaluated at two different test sessions the normality and variability of the isokinetic peak torque (PT), peak work (PW), peak power (PP) and peak torque acceleration energy (PTAE) data outputs in healthy adult males (n = 10) and females (n = 10). The hamstring and quadriceps muscles were tested at the angular velocities of 60 deg/s (a slow speed test) and 240 deg/s (a high speed test). The predictability of the PW, PP and PTAE from the PT was also assessed. The results showed that the consistency of the PW and PP measurements were equal with that of the PT. This was due to equal (almost normal) data distribution, equal variability of the outputs (the coefficient of variation (cv) ranged from 14 to 29% in the PWs and PPs versus 16 to 29% in the PTs), and excellent predictability of the PW and PP from the PT (PTs accounted on an average 85% for the variation seen in the PWs and PPs). In addition, in the regression analyses the standard errors of the estimates (SEEs) were low (less than 10%) and the residuals were distributed nonsystematically. In the PTAE measurements, the results were much more inconsistent, especially during the slow speed of the dynamometer. Compared with PT, PW and PP, the PTAE data distribution differed more frequently from normal distribution and the PTAE outputs showed higher variability. In addition, the PTAE outputs could not be acceptably predicted from the PT. In conclusion, the isokinetic PW and PP measurements can be recommended for clinical use, while the PTAE measurements should not be used routinely. PMID- 1601562 TI - Exercise training at and above the lactate threshold in previously untrained women. AB - We examined the effects of training at and above the lactate threshold in previously untrained women. Twenty-four untrained eumenorrheic women (age = 31.3 +/- 4.0 yrs, wt = 66.2 +/- 7.6 kg, ht = 166.4 +/- 5.8 cm) were assessed at baseline [during days 1-3 of the menstrual cycle (MC)] and every 4 MC after that (for 1 year) for VO2 and velocity (V) at LT, fixed blood lactate concentrations (FBLC) of 2.0, 2.5, and 4.0 mM, and Max. Subjects were assigned to control (C, n = 7), at LT/LT, trained 6 days/week at the velocity associated with LT, (n = 9) or above LT (greater than LT, trained 3 days/week at the velocity midway between V LT and V Max and 3 days/week at V LT, n = 8) groups. Exercise prescriptions were adjusted after each assessment and each group progressed similarly in weekly mileage. No between group differences were observed before training. After training the greater than LT group had significantly higher values than the C and /LT groups for LT (p less than 0.05). For FBLC of 2.0, 2.5, and 4.0 mM and Max, the greater than LT group values were greater than the C group (p less than 0.05). No differences were observed after training between the /LT and C groups. Although the greater than LT group had higher VO2 and V Max values than the /LT group after training, these differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601563 TI - Efficiency of trained cyclists using circular and noncircular chainrings. AB - The purpose of this study was to determine oxygen consumption (VO2), heart rate (HR) response, and rating of perceived exertion (RPE) of trained cyclists using noncircular and circular chainrings over a range of gears and pedal cadences. The subjects included 7 male cyclists (6 USCF licensed riders, 1 national qualifying triathlete). Each subject rode his own bicycle mounted on a wind-trainer at gears of 5.92 and 7.33 meters with noncircular and circular chainrings at pedal cadences of 50, 70, and 90 rpm. VO2, HR, RPE, and respiratory exchange ratio (RER) measurements were made during each of the 12 rides. Mean percent VO2max for each condition ranged from 28.7 +/- 2.1% with the 5.92 meter gear at 50 rpm to 83.4 +/- 4.3% using the 7.33 meter gear at 90 rpm. The results indicate no significant difference in any of the parameters measured between the two chainrings for any of the experimental conditions. The data indicate that the noncircular chainrings used in this study were not more efficient than the standard circular chainring for trained cyclists. PMID- 1601564 TI - Biathlon shooting performance after exercise of different intensities. AB - Biathletes commonly reduce their skiing intensity as they approach the firing line. However, it is not clear how the intensity of the previous exercise affects their shooting results. The purpose of this investigation was to assess shooting performance among elite American biathletes immediately after exercise of various intensities. Shooting performance was assessed from measures of shooting accuracy, shooting precision, and stability of hold. It was found that exercise intensity had minimal effect on shooting accuracy and precision for prone shooting, but did affect these measures for shooting in the standing position. In addition, stability of hold was affected more by exercise intensity for shooting in the standing position compared with prone shooting. If these results can be transferred to competitive biathlon, it is suggested that the intensity of exertion immediately prior to biathlon shooting has minimal influence on prone shooting performance, but does affect shooting in the standing position by altering the stability of the hold. PMID- 1601565 TI - Nifedipine diminishes exercise-induced muscle damage in mouse. AB - The purpose of this study was to evaluate the effects of a calcium channel blocker (nifedipine) on the severity of muscle damage induced by intensive exercise. Male Charles River mice were assigned to four groups (8 mice/group): normal control (C), nifedipine (N), nifedipine and exercise (N + E) and exercise (E). The animals of the C group were not submitted to any exercise nor to drug administration. The animals of the N group received 1 mg.kg-1 per day of nifedipine (Adalat 10 mg, Bayer AG), per os, during 3 days. The mice of the N + E group were submitted to a treadmill run (0 degree slope) at 1000 m.h-1 (80% of their maximal speed) for 1 hour. In this group, the administration of the drug was under the same conditions as for the N group. The administration started 24 h before the run. The E group was submitted to the same exercise protocol as the animals of N + E group. The soleus muscle was excised for light and electron microscopic evaluation using routine histological techniques. In the C and N groups no morphological alterations were detected. In the E group the number of alterations of striated pattern was twice that in the N + E group. The number of fibres with central nuclei was 35% in the E group but only 8% in the N + E group. The total number of damaged fibres was significantly higher in the E group. The results suggest that nifedipine may give protection to exercise-induced skeletal muscle damage in mouse, probably because the blocking of channels impaired Ca2+ influx; and the results of this study therefore confirm earlier contentions about the possible role of calcium ions in producing muscle damage after work. PMID- 1601566 TI - Ethnography as narrative discourse: community integration of people with developmental disabilities. AB - Quality of life is recognized as a critical variable in community integration of people with developmental disabilities. A major concern expressed in the literature is to establish a measure of congruence between the perception and experiences of these people and their social environment. In response to this concern, this study presents a framework of analysis based on ethnography as narrative of the old and the new. The old narrative is that of segregation, leading to confined form of space and time. The new narrative is that of interdependence achieved through cyclical form of space and time. It is argued that community integration of people with developmental disabilities has taken place in relation to linear form of time and space, perpetuating the old narrative of isolation and segregation. The new narrative of interdependence requires the accommodation of differences by the non-disabled. The quality of life for people with disabilities is then a function of accommodation of differences. PMID- 1601567 TI - Influences of a hand positioning device on upper-extremity control of children with cerebral palsy. AB - The aim of this study was to investigate the effects of a hand positioning device on aspects of upper-extremity movement control and muscular activity during a reaching task, and on visual-motor performance in a group of ten children with cerebral palsy. A three-dimensional (3D) motion analysis tracking system was used to monitor hand movement. The 3D path length, movement latency, movement time, average velocity, and the number of accelerations and decelerations (movement units) were measured. Muscle onset latencies of the anterior deltoid, triceps, brachioradialis, extensor carpi radialis, and flexor carpi ulnaris muscles were recorded by electromyography (EMG). A pencil-paper test specifically designed for this study was used to evaluate visual-motor function. Each subject was tested under two conditions (device on and device off). No significant results were found by comparing any parameter between conditions for all subjects combined, however, individual subject data revealed a trend towards an increased number of movement units, slower movement times, and decreased average velocity during the 'on' condition as compared to the 'off' condition. The average onset latencies for the EMG activity of the arm muscles showed differences between the on and off conditions, showing a more normalized muscle activation pattern for the 'on' condition. Furthermore, individual data inspection showed improved performance in the test of visual-motor function during the 'on' as compared to 'off' condition for most subjects. The potential clinical impact of the use of the device for some children with cerebral palsy, as well as directions for future research, are discussed. PMID- 1601568 TI - Respiratory problems in patients with high lesion quadriplegia. PMID- 1601569 TI - Arm amputation statistics for England 1958-88: an exploratory statistical analysis. PMID- 1601570 TI - Impact of rehabilitation on psychological distress: gender differences. PMID- 1601571 TI - Training parents of autistic children in Singapore. PMID- 1601573 TI - Heritability of growth curve parameters and heritability of final size: a simulation study. AB - Simulations of nestling growth in Great Tits (Parus major) were used to show the consequences genetic variation in the parameters of growth curves could have on the amount of genetic variation in final body weight. This was done for the case of good environmental conditions (i.e. adequate food supply), and for poor environmental conditions (food limitation). A three-parameter process-error growth model based on the Richards curve (Brisbin et al., 1986) was used. The three parameters were the asymptote, the shape, and the time to complete approximately 95% of growth. In simulations, where only the asymptotic value was heritable, genetic variation in final weight was larger under good conditions than under poor conditions. Food limitations decreased the amount of genetic variation and the heritability estimate of final size. Similarly, sib competition, (based on body size differences of nestlings within broods) combined with food limitations lowered heritabilities. Sib competition under good conditions had no effect on heritabilities. In contrast, when the time to complete approximately 95% of growth was heritable, heritabilities for final size were not lower under poor conditions either without or in the presence of sib competition. This model suggests that different amounts of genetic variation in final size under good and poor conditions could be linked to the amount of genetic variation present in the growth curve parameters. The results agreed with an empirical study on body weight in a passerine bird, the Great Tit, where only the asymptote displayed heritable variation and more genetic variance was expressed under good conditions. PMID- 1601572 TI - Survival and reproduction in Peromyscus leucopus in the laboratory: viable model for aging studies. AB - White-footed mice Peromyscus leucopus reared in our laboratory from wild-caught parents lived at least to 5.5 years. Once past weaning, over 80% of the mice lived at least until two years. Females maintained a constant weight whereas the weight of males increased until four years and decreased thereafter. At four years of age both sexes bred successfully with mates of the same age, but had lower success with younger mice. Some males and females reproduced at five years of age. PMID- 1601574 TI - Ontogenetic body form changes in three ecological morphotypes of anuran tadpoles. AB - Metamorphic vertebrate species are of particular interest in ecological and evolutionary studies because the decoupling of larval and adult growth patterns potentially allows adaptive diversifications of the separate stages. Larval and adult growth might be much more constrained if allometric patterns were constant throughout ontogeny. To better understand how differential growth patterns might contribute to tadpole diversification, we have analyzed growth allometries in relation to interspecific morphometric differences in Gastrophryne carolinensis, Acris gryllus, and Hyla gratiosa. Growth patterns in all species are significantly allometric and moderately concordant, despite many differences in detail. The species can be completely discriminated in even the smallest post hatching tadpoles. However, the differences that distinguish the species do not seem to be a function of differential growth patterns at the tadpole stage. Rather, morphological differences ostensibly originate during embryonic development and are well established by the time the tadpoles become free swimming. PMID- 1601575 TI - Morphometric studies in inbred and hybrid house mice. VIII. Effects of litter size on brain size and body size. AB - Litter size, brain size, and body size were examined in inbred and hybrid house mice of three different ages in order to test whether litter size exhibits a positive genetic, but negative environmental association with both brain and body size. As estimated from among-line covariation, litter size showed a positive, but non-significant genetical association with brain and body size. It also showed a significant, negative environmental association with brain and body size, as hypothesized. Over all inbreds and hybrids, litter size explained 8% and 14%, respectively, of the within-strain (environmental) variation in brain and body size. It was concluded that the negative phenotypic association of litter size with brain size and especially body size is the reflection of a well-known negative maternal environmental effect whereby mice with large body sizes tend to produce larger litters of mice with smaller body sizes. PMID- 1601576 TI - Age and sex-independent comparisons of morphological measurements. AB - A method is proposed for the comparison of morphological parameters that compensates for sex and age effects. An index is calculated for individual animals, from which percentage differences in size that are independent of age sex classes can be postulated for specific environmental effects. The method is appropriate for any data set that has a sufficiently broad age range to enable an accurate fitting of a growth curve, and thus overcomes the problem of using only fully mature animals for environmental comparisons. Besides detecting general size effects, the technique enables interpretation of changes at specific phases of the growth curve when more elaborate techniques for doing this are not appropriate. An hypothesised difference in size is confirmed between two fallow deer populations, living at different densities with different preferred food availability. The method is seen as being generally applicable, its appropriateness for any particular data set can be easily gauged, and the method itself is simple to apply. PMID- 1601578 TI - Assessing the technology of physical therapy. PMID- 1601577 TI - Growth allometry of organs, muscles and bones in mice from lines divergently selected on the basis of plasma insulin-like growth factor-I. AB - Growth allometry was examined over the range 6 to 112 days of age in male and female mice from lines selected for low (L) or high (H) plasma concentrations of insulin-like growth factor-I (IGF-I). Plasma IGF-I concentrations were greater in the H line than in L line mice from 28 days of age. H line mice also had greater liveweights and weights of the heart, kidneys, pancreas, lungs, liver, brain and testes from 21-28 days of age. Changes in weights of these organs reflected the general pattern of body growth, there being no consistent effects of selection line on allometric growth coefficients. Ovarian weights were not different between the lines. For muscle weights, (gastrocnemius, quadriceps femoris), the weights or lengths of bones (tibia, femur) and the nose-anus and anus-tail lengths, allometric growth coefficients were generally higher (P less than .05) in L line females than in L line males or H line mice of either sex. The allometric growth coefficient for spleen was significantly (P less than .05) greater in H line mice than in L line mice with the result that spleen weights were 30% higher in H line mice from 28 days of age. This is consistent with results from mice treated with, or transgenic for, IGF-I and suggests a specific effect of this hormone on growth of the spleen. Thymus weights were also greater in H line than in L line mice and developmental patterns of thymus weight closely paralleled those of circulating IGF-I. PMID- 1601579 TI - Correlates of physician utilization of physical therapy. AB - A survey of 200 physicians explored the relationship between their beliefs in the efficacy of physical therapy (PT) and their use of PT for their patients with cerebral palsy (CP). Results show that utilization of PT is related to physicians' use of PT in general and is inversely related to the percentage of CP in physicians' patient loads, but is not related to their opinions of the value of PT services. PMID- 1601580 TI - The relationship of technology assessment and utilization. Electromyographic feedback instrumentation as a model. AB - Biofeedback instrumentation has been a growing part of physical therapy practice for 20 years, and physical therapists have contributed to researching its efficacy in treating varying conditions. The application of biofeedback to the treatment of stroke was marked by some early difficulties with the quality of the electronics, but sophisticated contemporary equipment can do much more than was originally envisioned. The importance of relating quantified movement-based data to functional measures is projected as a high priority if appropriate reimbursement for physical therapy services with biofeedback is to continue in the future. PMID- 1601581 TI - Making information accessible and useful to practicing clinicians. Problem knowledge coupling. AB - Assessments of health care technology will lead to improvements in patient services only if this information is actually used by clinicians. Traditional methods of planning treatment that rely solely on memory limit the clinician's access to and use of the full available body of knowledge in the field. An alternative approach using a computer-assisted methodology is presented as a way to overcome traditional limitations and promote the development and diffusion of knowledge. PMID- 1601582 TI - Assessing the technology of developing health occupations: obstacles, risks, and strategies for future work. AB - Efforts to expand technology assessment in developing fields, such as physical therapy, face major obstacles. These impediments include scarcity of assessment tools, weak organizational structure for research, and clinicians' reluctance to assess economic factors. Risks that could accompany future work and strategies for reducing problems are discussed. PMID- 1601583 TI - Translating technology assessment into policy. Conceptual issues and tough choices. AB - Conceptual issues arise in translating the results of technology assessment into policy. A 3 x 3 typology suggests that tough decisions occur when interventions promise increased benefit for increased cost or less benefit for less cost. These decisions are value based; technology assessment alone cannot determine who should receive an intervention and under what circumstances. PMID- 1601584 TI - Medical equipment in the People's Republic of China. A survey of medical equipment procurement, utilization, and maintenance in university-affiliated hospitals between 1976 and 1987. AB - We report results of a survey of medical equipment purchasing, utilization, and maintenance practices in 12 Chinese tertiary-care hospitals. A dramatic increase in expenditures on medical equipment was found to have occurred after 1979, mainly resulting from purchases of imported equipment. Based on survey results and on personal observations, recommendations are given for reducing equipment related costs through the development of clinical engineering services. PMID- 1601585 TI - Technology assessment in a user perspective--experiences with drug technology. AB - Drugs have a central place among medical technologies, and medical technology assessment can learn from the established regulation of drug technology. This article outlines how users' experiences are not part of the basis on which decisions are made today, although this knowledge is imperative for identifying the problems that are not uncovered or foreseen by today's drug assessments. Further, users' interests might not be part of assessments that are based on the controlled clinical trial. A framework for drug technology assessments based on a user perspective is suggested. PMID- 1601586 TI - Treatment of symptomatic cholelithiasis in France. A decision analysis comparing cholecystectomy and biliary lithotripsy. AB - To determine the potential role of extracorporeal shock wave lithotripsy (ESWL) in the treatment of symptomatic gallstone patients in France, a simulation model evaluated the health and economic effects of three different treatment strategies. Decision analysis of conventional cholecystectomy alone and either of two strategies using a combination of biliary lithotripsy and conventional cholecystectomy reveals that a strategy employing biliary ESWL results in a significant number of successfully treated patients, thus avoiding the risks and costs of abdominal surgery. Moreover, cost analysis shows that expanding the use of lithotripsy to all patients for whom the procedure is indicated increases the average cost per successfully treated patient, but, more importantly, decreases the overall costs incurred by the cohort. From a societal viewpoint, a policy using biliary ESWL in appropriate patients is superior to one of cholecystectomy alone, from both clinical and economic perspectives. PMID- 1601587 TI - Clinical decision analysis as a means of technology assessment. The effectiveness of intraoperative cholangiography. AB - Three strategies for timely detection of common duct stones are examined by decision analysis: the use of intraoperative cholangiography (IOC) in ALL, NONE, or in SOME of the cases that are selected by the estimated probability of a common duct stone. Selective use of IOC is the most cost-effective option and offers a slightly lower mortality risk. PMID- 1601588 TI - The potential for medical informatics in the Eastern Mediterranean Region. AB - This article assesses the potential value of an integrated medical/ hospital information system (IMIS) for the members of the Eastern Mediterranean Region of the World Health Organization, and describes the preliminary results of a feasibility study questionnaire done in December 1989 at Salmaniya Medical Center (SMC) in the state of Bahrain. PMID- 1601589 TI - Crucial questions for physiotherapy in Finland. AB - When planning for health services, questions of production and distribution as well as cost and quality are key issues for health planners and decision makers. The lack of available objective data often makes this work difficult. This paper presents recent efforts in Finland to improve the collection of information needed for planning in the field of physiotherapy. PMID- 1601590 TI - Whom to treat first, and how much is enough? Ethical dilemmas that physical therapists confront as they compare individual patients' needs for treatment. AB - When there is a scarcity of resources (therapists, modalities), the physical therapist must make decisions about whom to treat and why. This paper discusses ethical dilemmas confronting the therapist and addresses solutions based on approaches of procedural justice and distributive justice. PMID- 1601591 TI - The Canadian Physiotherapy Quality of Care Project. Analysis of a derailed project. AB - The Physiotherapy Quality of Care Project was a project of the Canadian Physiotherapy Association, sponsored by the Canadian government to ensure the quality of physiotherapy. A consensus committee of physiotherapy educators and managers developed and tested an instrument to measure changes in patients' functional status during physiotherapy. Despite scientific development and wide distribution, this technology was not adopted. Alternative methods, which were heavily marketed, gained nationwide use instead. PMID- 1601592 TI - The history and present scope of physical therapy. PMID- 1601593 TI - Benesh Movement Notation. A tool to record observational assessment. AB - This article describes the introduction into physiotherapy practice of Benesh Movement Notation, a method for recording observations of patients' posture and movement sequences. Assessments of the technique show it to be a reliable and practical tool for clinical use. PMID- 1601594 TI - Describing patterns of recovery as a basis for evaluating progress. AB - Collecting descriptive data on patterns of recovery from a disabling condition could provide a baseline for assessing treatment methods and for monitoring the progress of individual patients. An illustrative study of patients recovering from stroke is presented and the strengths and weaknesses of such studies are discussed. PMID- 1601595 TI - Analyzing errors in practice. A vehicle for assessing and enhancing the quality of care. AB - Failures are inevitable in health care. When failure occurs as a result of practitioner error, quality in patient care may be compromised. This article proposes that analyzing clinical errors may contribute to quality assurance. Examples from physical therapy illustrate how information gained from analyzing errors can enhance patient care. PMID- 1601596 TI - Outcome assessment in cardiac rehabilitation. AB - Cardiac rehabilitation outcome assessment has reflected the isolated concerns of different professionals, each addressing different factors of the problems of patients. Physical, medical, psychosocial, and epidemiological approaches have been taken. Discrepancies in findings may relate more to problems with assessment than to the technology itself, and can undermine the usefulness of the intervention. PMID- 1601597 TI - Development of a program for the treatment of chronic pain and anxiety. A learning process leading from unsound to sound assessment. AB - The development and assessment, over a 10-year period, of a technology for group treatment of patients with chronic pain and anxiety is described. Positive results, such as a decrease of symptoms and improved self-confidence, have stimulated diffusion of the technology to colleagues and have increased our own involvement in the organization of services. PMID- 1601598 TI - Hospital care versus home care for rehabilitation after hip replacement. AB - A pilot study was done to assess the feasibility of reducing the hospital stays of patients with total hip replacement (THR). The length of hospital stay for these patients depends largely on how rehabilitation, mostly physical therapy, is organized. This study shows that not more than a half hour per postoperative day was devoted to care services and rehabilitation activities. It is feasible and less expensive to reduce substantially hospital stay by planned physical therapy in the patient's home. These results have prompted a randomized controlled clinical trial to assess hospital versus home rehabilitation. PMID- 1601599 TI - Fostering research by radiologists: recommendations of the 1991 Summit meeting. PMID- 1601600 TI - Ultrasonic detection of osteomyelitis. Pathologic correlation in an animal model. AB - The authors correlated sonographic findings with histologic findings in a rabbit model of osteomyelitis. Staphylococcus aureus osteomyelitis was induced in the femora of 11 New Zealand white rabbits. The opposite leg was used as a control. Sonographic findings showed fluid adjacent to the bone in 11 cases. The fluid was believed to be an inflammatory exudate, and its presence suggested osteomyelitis. Pathologic analysis showed extraperiosteal purulent fluid adjacent to the cortex as well as histopathologic changes of osteomyelitis in the 11 rabbits. There was one false-positive sonographic diagnosis of osteomyelitis in a rabbit that had a soft tissue abscess adjacent to the cortex. PMID- 1601601 TI - Contrast media-induced renal tubular vacuolization after dehydration. A light and electron microscopic study in rats. AB - Morphologic studies on the effect of dehydration on contrast media (CM)-induced renal changes were done. Sixty-six healthy Wistar rats were deprived of water for 24 hours before the intravenous (i.v.) injection of 1.0 or 3.0 g iodine (I)/kg of high-osmolal diatrizoate, low-osmolal iopromide or iohexol, iso-osmolal iotrolan, or 0.2 or 0.6 g/kg of high-osmolal magnetic contrast agent, gadolinium-DTPA (Gd DTPA). Control animals received physiologic saline. After 2 hours, the kidneys were fixed by perfusion for light and electron microscopy, and the morphologic changes were semi-quantitatively reviewed by two independent observers blinded to the treatment. The smaller dose of iohexol or iotrolan and the larger dose of all the CM induced in the proximal convoluted tubule (PCT) cells a statistically highly significant (P less than .001) or significant (Gd-DTPA; P less than .01) cytoplasmic vacuolization. The changes were most prominent (P less than .001) after treatment with iohexol and iotrolan. The results might be related to the higher urinary CM concentration after low- and iso-osmolal agents. Dehydration further potentiates higher CM concentration. The morphologic injury, when compared with the author's earlier findings on normal rats, was clearly intensified by dehydration. PMID- 1601602 TI - Posterior beam-stop method for scatter fraction measurement in digital radiography. AB - The authors presented a new posterior beam-stop (PBS) technique for measuring the ratio of scattered to total-detected photon flux (scatter fraction) in a radiographic examination while preserving the diagnostic quality of the image. The scatter measurement was made using a standard imaging geometry with both beam stops and an additional x-ray detector placed behind the standard imaging detector. This PBS geometry differs from the standard beam-stop (SBS) technique for scatter measurement. With SBS, a beam-stop shadow appears on the image. To evaluate the PBS technique, scatter fraction measurements were performed on an anatomic phantom using both the PBS and SBS techniques. When compared with the standard technique, PBS provided accurate estimation of scatter fractions. Since the measurement can be performed without degrading a standard clinical radiographic examination, the PBS technique allows simultaneous acquisition of scatter measurements from human patients in combination with a standard radiographic examination. PMID- 1601604 TI - Human pharmacokinetics of iodixanol. AB - The pharmacokinetic properties of the x-ray contrast medium, iodixanol, a new nonionic dimer, were investigated in a phase I study including 40 healthy male volunteers. Iodixanol (300 mg I/mL) was administered intravenously (i.v.) at four dose levels--0.3, 0.6, 0.9, and 1.2 g iodine (I)/kg body weight--and saline was given as a control. 51Cr-EDTA was given concomitantly with iodixanol at all dose levels to study renal excretion of iodixanol. Mean half-lives were 26 and 131 minutes in the distribution and elimination phase, respectively. Apparent volume of distribution was 0.28 1/kg body weight, indicating distribution to extracellular fluid only. Within 24 hours after injection, 97% of the dose was excreted unmetabolized in the urine via glomerular filtration. The excretion in feces was 1.2% of the dose. The parameters calculated were independent of the given dose. The pharmacokinetics of iodixanol are comparable with those reported for other intravascular contrast media. PMID- 1601603 TI - Computerized scheme for the detection of pulmonary nodules. A nonlinear filtering technique. AB - To aid radiologists in the detection of lung cancer, the authors are developing a computer-aided diagnosis system that locates areas suspicious for nodules in digital chest radiographs. The system involves a difference-image approach and various feature-extraction techniques. The authors describe nonlinear filters used in the difference-image approach. A morphological open operation and a ring shaped median filter are applied in the difference-image step for signal enhancement and signal suppression, respectively. Using 60 clinical chest radiographs, the nonlinear filtering method detected approximately 63% of actual nodules with approximately 19 false-positive results per image. The locations of the false-positive detections, however, usually did not coincide with those from the linear filtering method. Thus, by using a combination of the detections from the two methods, the false-positive rate was reduced to two to three per image at a sensitivity of 60%. PMID- 1601605 TI - The acceleration of gallstone destruction with synchronous biliary lithotripsy and contact dissolution in vitro using three cholesterol-solubilizing solvent. AB - In the first-known application of its kind, shockwave lithotripsy and contact solvent dissolution of large, calcified gallstone burdens were performed simultaneously with three chemical solvents, each tested separately in an in vitro model, with the combined effects on gallstone eradication examined. Two solvents, ethyl propionate and isopropyl acetate, were chosen for their solubilizing ability and potentially high level of patient safety. The third solvent, a 70%:30% mixture of methyl tert-butyl ether (MTBE) and dimethyl sulfoxide (DMSO), was chosen for its known ability to accelerate the dissolution of calcium-containing gallstones. All stones were matched for size, weight, and number. Gallstone lithotripsy performed in ethyl propionate was significantly more effective (P less than .02) in the production of fragments less than 2 mm when compared with bile; lithotripsy with isopropyl acetate and the MTBE/DMSO mixture showed no statistically significant effect. Biliary lithotripsy performed in an ethyl propionate medium may enhance gallstone dissolution and the production of small fragments (diameter less than 2 mm). PMID- 1601606 TI - Preservation of high-energy phosphate reserves in a cat model of post-ischemic myocardial dysfunction. AB - Brief episodes of myocardial ischemia are known to cause reversible depression of regional myocardial contraction after reperfusion. One of the mechanisms of this persistent regional dysfunction has been proposed to be depletion of high-energy phosphate compounds. Eight cats were prepared with a reversible snare occluder around the left anterior descending artery (LAD); a surface coil sutured to the epicardial surface over the LAD territory for measurement of 31-phosphorus (31P) magnetic resonance spectroscopy (MRS) spectra; and a pair of ultrasonic crystals implanted in the mid-myocardium for measurement of regional segment length shortening. The baseline value of percent segment length shortening (%SS) was 12.8 +/- 1.4%. Increased afterload did not significantly alter high-energy phosphate levels or %SS. All animals exhibited passive systolic bulging during occlusion (-8.4 +/- 3.6% systolic shortening) as well as reduced phosphocreatine (PRc, 30 +/- 3% of control) and increased inorganic phosphorus (Pi) (239 +/- 18%), but there was no change in adenosine triphosphate (ATP). During reflow, %SS did not completely recover (4.0 +/- 2.9%, P less than .05 versus baseline). PCr and Pi returned to control levels during the first 30 minutes of reperfusion. Increased afterload had no significant effect on high-energy phosphates or %SS in stunned hearts. These findings indicate a lack of correlation between recovery of high-energy phosphate stores and regional myocardial contractility in stunned myocardium. High-energy phosphate reserves are preserved in stunned myocardium and are unlikely to be a direct cause of myocardial dysfunction. PMID- 1601607 TI - Renal tolerance of gadolinium-DTPA/dimeglumine in patients with chronic renal failure. AB - Safety data for renal tolerance of gadolinium-DTPA(Gd-DTPA)/dimeglumine were evaluated in 21 patients (age: mean +/- standard deviation [SD], 58 +/- 12 years) with impaired renal function. The mean +/- SD serum creatinine level at baseline was 213 +/- 101 mumol/L (range, 89.2-551 mumol/L). Creatinine clearance at baseline averaged 34.5 +/- 19.2 mL/minute (range, 7.2-70 mL/minute). Gd-DTPA was injected at a dose of 0.1 mmol/kg body weight. Serum parameters (creatinine, sodium, and potassium) were determined before and 6, 24, 48, and 120 hours after administration of Gd-DTPA. Urinary parameters (N-acetyl-beta-D-glucosaminidase [beta-NAG], protein, and albumin) were determined before (spot urine sample) and after treatment for collection periods 0 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 48 hours. A final spot urine sample was taken at 120 hours. There was no significant statistical change of serum creatinine level within the observation period, and there was no single patient matching the criteria of acute renal failure (increase of serum creatinine level of 88.4 mumol/L [1 mg/dL] or more within 48 hours after injection). Serum values of sodium and potassium levels remained unchanged. Beta-NAG was slightly increased 0 to 3 hours after injection, but returned to baseline values during the collection periods up to 120 hours. There was no increase of protein or albumin excretion. These preliminary results suggest Gd-DTPA has good renal tolerance in patients with pre-existing chronic renal failure. PMID- 1601608 TI - A probe for specimen magnetic resonance microscopy. AB - One of the primary limits to spatial resolution in magnetic resonance (MR) microscopy is the limited signal. The purpose of this study is to build a radiofrequency (rf) probe for MR microscopy of fixed specimens at 300 MHz. The design criteria for the probe were (1) high sensitivity; (2) good rf homogeneity; (3) minimization of BO variations. All probes were Helmholtz pairs operating at 300 MHz. Coils were constructed from copper/Teflon/copper microwave substrate which eliminated susceptibility problems from solder and discrete capacitors. Signal-to-noise ratio (SNR) was compared with a conventional solenoid. Phantoms of agar gels and saline-filled tubes were used to characterize the SNR and homogeneity. SNR measurements of the coil pairs showed a marked improvement (up to 60%) over that of the reference solenoid. The region of homogeneity was defined as a 10% variation in signal intensity. This correlated with the coil's inner diameter. Graphs of SNR versus diameter, separation, and copper foil width allowed for optimization of the structure. Using this coil, MR microscopy is now possible on small, fixed specimens with pixels as small as 20 x 20 x 30 microns. Work is currently under way exploiting the SNR and homogeneity provided by this probe to determine the degree to which MR microscopy might add to the pathologists' diagnostic tools. PMID- 1601609 TI - Positron emission tomography as a diagnostic tool. A reassessment based on literature review. AB - Currently used clinical diagnostic imaging modalities, such as magnetic resonance imaging (MRI) and x-ray computed tomography (CT) provide predominantly anatomic information. CT images reflect x-ray attenuation distribution in the body, whereas MRI signals depend primarily on proton density and tissue relaxivity. In contrast to these predominantly anatomic modalities, positron emission tomography (PET) reflects tissue physiology and metabolism. Although PET has been used predominantly as a research tool, the clinical use of this technique for the detection, noninvasive characterization, and treatment planning of selected disease processes has been extensively studied in oncology, cardiology, and neurology. The author examined currently available literature to reassess the potential role of PET as a diagnostic tool in the following specific clinical situations: (1) the differentiation of radiation necrosis from tumor recurrence; (2) the characterization of the physiologic significance of coronary stenosis and the evaluation of the myocardial viability; and (3) the localization of the epileptogenic foci. PMID- 1601610 TI - The use of continuous and discrete confidence judgments in receiver operating characteristic studies of diagnostic imaging techniques. AB - Virtually all receiver operating characteristic (ROC) studies of medical imaging methods have involved data collected on a discrete confidence-rating scale, though in principle ROC studies can be conducted with either discrete or continuous scales. Continuous scales provide potential advantages in medical applications of ROC analysis, but the possible dependence of ROC results on the kind of scale used in an observer-performance experiment has not been investigated empirically. The authors conducted a multi-observer ROC study in which radiologists read abdominal computed tomography (CT) examination results displayed on a workstation with a high-resolution video monitor. Ninety-five examinations were evaluated by five radiologists who reported their confidence concerning the presence of abdominal masses on a conventional five-category discrete scale and, in a separate reading session, on a continuous subjective probability scale. ROC analysis showed no statistically significant difference between the detection accuracies (Az) achieved with the two scales by any reader. Accuracies averaged over all readers were identical with the two scales. The results of this study suggest that discrete or continuous scales often can be used interchangeably in image-evaluation studies. However, the authors recommend continuous scales for routine use in radiologic ROC studies because of their potential advantages in some situations. PMID- 1601611 TI - First-year medical students' attitudes toward radiology. AB - To explore the perspectives of entering medical students, a questionnaire was completed anonymously by 171 students in September of their first year of medical school. The authors investigated their attitudes toward radiology relative to other specialties and their perspective concerning which factors would influence their eventual choice of a specialty. Upon entering medical school, 33.3% of the students indicated that they had chosen a specialty, and 7.4% of these students had selected radiology. Radiology was perceived as a well-paid specialty with a pleasant lifestyle. These are factors that were perceived as very important regarding influence on eventual choice of specialty. However, radiology was believed to have an undesirably low level of patient contact and was perceived as not being intellectually exciting. We plan to follow this group of students prospectively through medical school to see whether their attitudes change toward radiology as a career. PMID- 1601612 TI - Post-angiographic blindness in a patient with sickle cell disease. AB - This article described a 19-year-old woman with homozygous sickle disease in whom multiple cerebral infarcts developed after a technically uncomplicated cardiac angiogram. The article highlighted the risks of hyperosmolar solutions in patients with sickle cell disease and emphasized that only low osmolar contrast media, nonionic or ionic, should be used. PMID- 1601613 TI - A statistically significant difference between glass and plastic syringes, with risk of clotting greater in glass than in plastic. PMID- 1601614 TI - Radiology resident education: instilling an appreciation of the medical literature. PMID- 1601615 TI - Administration: an appropriate training subject? PMID- 1601616 TI - Evaluation of marrow perfusion in the femoral head by dynamic magnetic resonance imaging. Effect of venous occlusion in a dog model. AB - RATIONALE AND OBJECTIVES: There is a continuing need for a greater sensitivity of magnetic resonance imaging (MRI) in the diagnosis of avascular necrosis (AVN). Previously, it was demonstrated that a dynamic MRI method, with gadolinium-DTPA (Gd-DTPA) enhancement, can detect acute changes not seen on spin-echo images after arterial occlusion in a dog model. Because venous congestion appears to be a more directly relevant hemodynamic abnormality in a majority of clinical AVN cases, the authors extended the dynamic MRI technique to study changes in venous occlusion. METHODS: Dynamic MRI of the proximal femur was performed in five adult dogs before and after unilateral ligation of common iliac and lateral circumflex veins. Sixteen sequential gradient-recalled pulse sequence (GRASS) images (time resolution = 45 mseconds, echo time = 9 mseconds, flip angle = 65 degrees) were obtained immediately after a bolus intravenous injection of 0.2 mmol/kg of Gd DTPA. Simultaneous measurements of regional blood flow were made using the radioactive microsphere method. RESULTS: After venous ligation, there was a 25% to 45% decrease in the degree of enhancement compared with preligation values on the ligated side. The decrease in cumulative enhancement (integrated over the entire time course) was statistically significant. The occlusion technique was verified by confirming a statistically significant decrease in blood flow determined by the microsphere method. CONCLUSIONS: Dynamic Gd-DTPA-enhanced fast MRI technique can detect acute changes in bone marrow perfusion due to venous occlusion. This technique may have applications in the early detection of nontraumatic AVN. PMID- 1601617 TI - Lactate mapping in ischemic rat kidneys using 1H spectroscopic imaging. AB - RATIONALE AND OBJECTIVES: Biochemical studies have shown that during renal ischemia, lactate is built up predominantly in the medulla and less in the cortex. The authors intend to confirm such a difference in lactate concentration between these two zones of the kidney by means 1H magnetic resonance (MR) spectroscopy. METHODS: In 10 rats, the authors used four-dimensional (n = 4) and three-dimensional (n = 6) spectroscopic imaging to investigate the left kidney after occlusion of the renal artery. RESULTS: By this technique, a map of the intrarenal lactate distribution was obtained during ischemia. It was determined that lactate concentration is indeed higher in the medulla than in the cortex, as verified by chemical analysis (17 +/- 4 versus 9 +/- 4 mumol/g). CONCLUSIONS: By correlating biochemical and morphologic information, localized MR spectroscopy combined with imaging is a powerful tool for investigating pathophysiologic mechanisms. PMID- 1601618 TI - Magnetic resonance perfusion/diffusion imaging of the excised dog kidney. AB - RATIONALE AND OBJECTIVES: The authors developed a model of tissue capillary beds applicable to perfusion/diffusion imaging with magnetic resonance imaging (MRI). The model consists of a formalin-fixed excised dog kidney attached to a variable speed pump. With this system, it is possible to perfuse the kidney at selected rates. METHODS: Using the intravoxel incoherent motion model (IVIM), the apparent diffusion coefficient (ADC), diffusion coefficient (D), and perfusion fraction (f) were computed for a region of interest (ROI) in the renal cortex and in the medulla of seven kidneys, one of which was injected with a vasodilator before fixation. ADC and D values were computed for both cortex and medulla. These values were normalized to zero flow and plotted against renal perfusion. The perfusion fraction f was expressed in percent and was not normalized to zero flow. RESULTS: Normalized ADC and f were correlated with tissue perfusion rates using the Spearman rank-sum test (n = 18, rs greater than 0.5, P less than or equal to .02 for the standard preparation in both cortex and medulla), whereas normalized D (rs much less than 0.5) was uncorrelated for both preparations in cortex and medulla. CONCLUSIONS: The isolated perfused dog kidney is a useful model of tissue capillary beds for perfusion imaging technique development. The perfusion/diffusion-related parameters ADC and f increase as flow increases in the tissues, whereas D does not. PMID- 1601619 TI - Lymphatic imaging in experimental filariasis using magnetic resonance. AB - RATIONALE AND OBJECTIVES: To evaluate acquired lymphatic abnormalities caused by filariasis, the authors examined the peripheral lymphatic system in normal ferrets and those chronically infected with Brugia malayi using magnetic resonance imaging (MRI). The findings were compared with previously obtained lymphangioscintigraphic (LAS) images in ferrets both with and without experimental filariasis. METHODS: Fifteen ferrets (11 infected with B. malayi and four noninfected controls) underwent whole body coronal MRI using a quadrature transmission-receive head coil at 0.5 Tesla operating at a resonant frequency of 21.5 mHz for protons with a 25-cm field of view. RESULTS: In contrast to normal animals, infected ferrets showed dilated hindlimb dermal lymphatic collaterals, enlarged high-signal intensity groin lymph nodes with punctate low-signal intensity centers and separate low-signal intensity spots with irregular thin channels, suggestive of nests of viable adult nematodes within tortuous lymphatics and nodes. MRI correlated with the LAS findings, and the interpretations were supported by light, scanning electron, and video microscopy. CONCLUSIONS: T2-weighted MRI in conjunction with LAS accurately depicts the peripheral lymphatic system in filarial-infected ferrets. These two modalities are useful complementary techniques to examine disorders characterized by lymphatic insufficiency. PMID- 1601620 TI - Evaluation of the integrity of the blood-brain barrier after meningeal trauma. AB - RATIONALE AND OBJECTIVES: The authors used magnetic resonance imaging (MRI) techniques to examine the effect of meningeal trauma produced by cisterna magna puncture on the integrity of the blood-cerebrospinal fluid barrier (BCB) in a rat model. METHODS: Intravenous gadolinium-DTPA (Gd-DTPA), a relaxation rate modifier which normally does not cross the BCB, was used as a probe to follow leakage of fluid across the BCB. After Gd-DTPA injection, cerebrospinal fluid (CSF) serial samples were obtained through the needle used to create the experimental trauma. These samples were subsequently examined in vitro by MRI to obtain their T1 relaxation rates and assayed by mass spectrometry for gadolinium and elemental iron concentrations. RESULTS: The iron levels reflected the severity of puncture related subarachnoid hemorrhage. Rats with ongoing meningeal damage showed significantly higher CSF levels of gadolinium and significantly higher CSF T1 relaxation rates than controls at all samples times over 1 hour after the puncture. Blood in the CSF could not explain these changes because the CSF iron levels did not significantly differ from control levels. CONCLUSIONS: Intravenously administered Gd-DTPA can gain access to the subarachnoid space through minor defects in the BCB and cause significant increases in CSF T1 relaxation rates. PMID- 1601621 TI - Myocardial volume perfused by coronary artery branches. A three-dimensional X-ray computed tomographic evaluation in pigs. AB - RATIONALE AND OBJECTIVES: The authors tested the hypothesis that the cumulative length of arterial branches is related to the volume of tissue they perfuse. This experiment investigates the potential value of this approach for assessing the volume of myocardium at risk in cases of coronary occlusion. METHODS: The volume of myocardium perfused by coronary arterial branches and the cumulative length of the main feeder branches perfusing that volume were measured in vivo in pig hearts from multislice computed tomographic (CT) images of the heart, recorded during an aortic root injection of nonionic contrast agent. RESULTS: The relationship between the volume (V, in milliliters) of perfused myocardium and the length (L, in millimeters) of the left anterior descending artery was V = 42.4 x 10(-0.011L) (r = -0.892); for the right coronary artery, V = 37.0 x 10( 0.008L) (r = -0.888); and for the left circumflex coronary artery, V = 27.7 x 10( 0.011L) (r = -0.883). CONCLUSIONS: These results suggest that the maximum volume of myocardium at risk of infarction due to blockage along a coronary artery could possibly be estimated from the three-dimensional geometry of the epicardial coronary arterial tree. PMID- 1601622 TI - Screening test for detection of metallic foreign objects in the orbit before magnetic resonance imaging. AB - RATIONALE AND OBJECTIVES: A study was designed to determine whether plain films, used as a screening modality for magnetic resonance imaging (MRI), could reliably detect intraorbital metallic foreign objects. METHODS: In the first experiment, 20 metal particles were placed in five human cadaver orbits. Routine orbital plain film series and computed tomography (CT) were obtained, randomized, and interpreted blinded by three experienced radiologists. RESULTS: The threshold size of particle detection for CT (0.07 mm3) was lower than for plain films (0.12 mm3). Placing metal particles in artificial and true vitreous demonstrated that all particles moved under a magnetic field at 1.5 T. When human globes were exposed to industrial tools (grinder, bandsaw, air hose, etc.), no metal objects penetrated the sclera. CONCLUSIONS: Plain films can be used as a low-cost, low radiation screening procedure for high-risk patients with occupations involving metal work. CT should be used for patients with a history of eye trauma from other causes. PMID- 1601623 TI - Noninvasive liver-iron quantification by computed tomography in iron-overloaded rats. AB - RATIONALE AND OBJECTIVES: The benefit of computed tomography (CT) for the noninvasive determination of liver-iron concentration in human iron-overload diseases is a controversy in the literature. To study the sensitivity of CT for liver-iron quantification under experimental conditions, the authors measured single- and dual-energy CT numbers in vivo in the livers of iron-overloaded rats. METHODS: Thirty-five rats were subjected to an iron-rich diet for various periods, from 1 to 20 weeks, then scanned by single- and dual-energy CT. CT absorption was correlated to liver-iron content, which was determined by wet ashing and spectrophotometry. RESULTS: Whereas a good correlation (r = 0.99 at 96 kV; r = 0.95 at 125 kV) between CT numbers and liver-iron concentration was found, CT was insensitive to low concentrations of iron. Dual-energy CT scanning results showed greater scattering in liver-iron quantification compared with single-energy CT. CONCLUSIONS: In rats, the sensitivity of single- and dual energy CT is too low to quantify liver iron in the diagnostically most relevant region of mild liver siderosis (1-3 mg iron/g wet weight [w.wt]). PMID- 1601624 TI - Thick-section, single breath-hold magnetic resonance pulmonary angiography. AB - RATIONALE AND OBJECTIVES: Approaches to performing magnetic resonance angiography (MRA) of the pulmonary vasculature are described using very fast (repetition time [TR] less than 13 mseconds) radiofrequency (rf)-spoiled, gradient-recalled pulse sequences and the standard quadrature body imaging coil of a commercial 1.5-T MR imaging system. METHODS AND RESULTS: Signal-to-noise (SNR) is improved by signal averaging (Nex greater than or equal to 4) in a two-dimensional, single thick section approach and by volume acquisition (Nex = 1) in a three-dimensional approach. Blood signal loss is minimized by using short, asymmetric echoes (echo time [TE] less than or equal to 2.7 mseconds). Respiratory motion is eliminated by keeping the scan time short enough (approximately 15 seconds) for image acquisition within a single breath-hold. Cardiac motion artifacts are reduced with section orientations that avoid intersecting the heart and/or use of small flip angle (alpha less than or equal to 25 degrees). CONCLUSIONS: Images of healthy volunteers showed that while single thick sections have superior SNR, the three-dimensional approach appears to produce better visualization of the peripheral vascular segments and offers improved ability to process the images to remove overlapping structures. PMID- 1601625 TI - Inexpensive technique for performing magnetic resonance-pathologic correlation in cadavers. PMID- 1601626 TI - The operating room of the future. Report of the National Cancer Institute Workshop, "Imaging-Guided Stereotactic Tumor Diagnosis and Treatment". PMID- 1601627 TI - Breast masses in two women with steatocystoma multiplex. PMID- 1601628 TI - Chest radiography: comparison of high-resolution digital displays with conventional and digital film. PMID- 1601629 TI - Epidemiological survey of multiple sclerosis in Catania city. AB - The findings of an epidemiological survey of multiple sclerosis (MS) in the urban area of Catania reveal a new and in some respects original pattern of MS cases recorded on 31 December 1989 (prevalence day). They explain why special attention should be paid to patients residing in that area, which shows a remarkable upward trend of the MS prevalence rates calling for further study and for more targeted intervention in the fields of prevention, treatment and rehabilitation. PMID- 1601630 TI - Follow-up of nerve conduction in chronic uremic patients during hemodialysis. AB - We studied to evolution of nerve conduction during hemodialysis following 21 patients with chronic renal failure. Mean motor nerve conduction velocity (MCV) was significantly different at hemodialysis onset and 3 years later for both common peroneal nerve (44.5 and 41.0 m./sec.) and ulnar nerve (52.5 and 47.1 m./sec.). MCV decreased more in patients with low Kt/V (a depuration index) than in those with high Kt/V. PMID- 1601631 TI - Mini-Mental State Examination (MMSE): sensitivity in an Italian sample of patients with dementia. AB - The sensitivity of the Mini-Mental State Examination (MMSE) was assessed in a sample of patients with dementia of the Alzheimer type or vascular dementia. The MMSE identified the majority of pts with diffuse cognitive impairment but did not discriminate between the two types of dementia. If failed to detect mild deterioration or forms in which only some cognitive functions were impaired. The test is therefore not sufficient for distinguishing deteriorated from non deteriorated pts, although it is still useful in mass screening or for a quick assessment of deterioration in the course of clinical neurological examination. PMID- 1601632 TI - Tension type headache: a neuropsychological and neurophysiological study. AB - Characteristic personality profiles of patients suffering from either migraine headache (MH) or tension type headache (TTH) have been described in the light of Minnesota Multiphasic Personality Inventory (MMPI). In the present study we evaluated personality profile changes following modifications of the painful symptoms after treatment, through the administration of the MMPI to MH and TTH patients. In TTH patients with no clinical improvement the depression scale scores were higher after 6 months of treatment, whereas in MH patients similar scores were observed before and after therapy, thus suggesting a primary role of depression in the onset of pain in the latter patients. Computerized EMG recording of the neck muscle activity showed different patterns of muscle contraction in resting condition and during stress or maximal muscular activity in patients suffering from TTH as compared to MH patients and normal subjects. PMID- 1601633 TI - The short latency muscle reflex in the diagnosis of disc disease affecting roots L4 and L5. AB - A segmental monosynaptic reflex that can be evoked by using voluntary muscle contraction to facilitate it is of use in diagnosis. In a group of 15 healthy volunteers the reflex response from tibialis anterior proved to be 31.08 +/- 2.48 msec with a side difference of 0.41 +/- 0.36 msec and from peroneus longus 29.90 +/- 2.20 msec with a side difference of 0.38 +/- 0.25 msec. Of 21 patients with radiologically proven disc herniation (of root L4 in 5 and of root L5 in 16) 16 showed a delay of more than 2.5 SD of the side difference or no response at all. It is hope that this simple and speedy method will be routinely adopted as complement to standard electromyography. PMID- 1601634 TI - Solitary plasmacytoma: a case report. AB - We report a case of solitary vertebral plasmacytoma that was peculiar in mode of onset and neurological course. The clinical and radiological evidence pointed to a generic diagnosis of epidural osteolytic process while electroimmunophoresis of blood narrowed the diagnosis to spinal plasmacytoma, confirmed at operation. PMID- 1601635 TI - Kleine-Levin syndrome in an 82 year old man. PMID- 1601636 TI - Acute intermittent porphyria. A perplexing case. AB - We report the case of a 58-year-old woman affected by polyneuropathy, vegetative disturbances and abdominal pain. A provisional diagnosis of acute intermittent porphyria was made and was confirmed by the increased levels of urinary delta aminolevulinic acid (ALA) and porphobilinogen (PBG). PMID- 1601637 TI - Late onset unilateral asterixis secondary to posterior cerebral artery infarction. AB - Unilateral asterixis developed in a 56 year old man, 5 months after an infarct in the posterior cerebral artery territory, involving the posterolateral nuclear complex of the thalamus, documented by CT-scan and MRI. Unilateral asterixis in rarely reported in association with thalamic lesions and usually develops as an immediate postictal phenomenon. We discuss possible physiopathological mechanisms explaining the occurrence and the delayed onset of these involuntary movements. PMID- 1601638 TI - Elsberg syndrome: radiculomyelopathy and acute urinary retention in patient with genital herpes. AB - We describe a case of a sexually active woman who presented acute urinary retention associated with herpes genitalis infection and with few other neurological signs. The outcome of the disease was positive. We stress the utility of a careful CSF examination. PMID- 1601639 TI - Immunomodulation of proteoglycan-induced progressive polyarthritis by leflunomide. AB - Proteoglycan-induced arthritis is a mouse model displaying many similarities to human rheumatoid arthritis and ankylosing spondylitis which has been documented by clinical and histopathological studies. The development of the disease in genetically susceptible BALB/c mice is dependent upon the expression of both cell mediated and humoral immunity to host mouse cartilage proteoglycan. Since both development and regression of acute inflammatory processes in joints correlate directly with the serum antibody level to mouse cartilage proteoglycan, it is believed that these autoreactive antibodies may play a key role in the pathological mechanism of proteoglycan-induced arthritis. The treatment of arthritic animals with an immunomodulating agent (leflunomide) suppressed acute inflammatory events, protected animals from new inflammatory episodes or acute exacerbations in chronically inflamed joints and blocked pathological processes in arthritic joints, which otherwise led to progressive deformities, ankylosis and the loss of articular cartilage. We conclude that the suppressive effect of leflunomide (HWA 486) in proteoglycan-induced arthritis primarily is due to the suppression of autoantibody formation and that the drug may be a potential agent in human therapy as well. Further, we feel that this novel model of murine polyarthritis will extend further the pharmacological repertoire necessary to discover innovative antirheumatic drugs. PMID- 1601640 TI - Distinction between the in vitro and in vivo inhibitory effects of morphine on lymphocyte proliferation based on agonist sensitivity and naltrexone reversibility. AB - We have previously reported that administration of a single dose of morphine (25 mg/kg) to rats results in a naltrexone-sensitive suppression of mitogen stimulated lymphocyte proliferation. To further delineate the site of action of this inhibitory effect, the in vitro and in vivo effects of morphine on mitogen stimulated lymphocyte proliferation were examined. In vitro, concentrations of morphine exceeding 0.1 mM exhibited a dose-dependent inhibition of Concanavalin A induced proliferation of both whole blood and splenic lymphocytes. This inhibitory effect of morphine on lymphocyte proliferation was not attenuated by co-incubation with the opioid antagonist naltrexone (0.25 mM). These data indicate that the in vitro inhibitory effects of morphine occur at only high concentrations and are not opioid receptor mediated. In vivo, a dose-dependent inhibition of blood lymphocyte proliferation was also observed 2 h following the subcutaneous injection of morphine. In contrast to these effects, proliferation of splenic lymphocyte cultures was not significantly inhibited by morphine at doses of up to 40 mg/kg. However, following morphine administration, a greater than 90% inhibition of proliferation was obtained in cultures containing either whole blood or Ficoll-separated lymphocytes, indicating that plasma was not a contributory factor in the differential sensitivity of blood and splenic lymphocyte responses to morphine. Moreover, in these experiments, significant inhibition of lymphocyte proliferation occurred at plasma concentrations that were two orders of magnitude less than those required to produce inhibition in vitro. The in vivo inhibition of lymphocyte proliferation by morphine (10 mg/kg) was completely antagonized by pretreatment with naltrexone (5 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601641 TI - Effect of testosterone on the eosinophil response of C57BL/6 mice to infection with Brugia pahangi. AB - The kinetics of peripheral and bone marrow eosinophil responses of C57BL/6 mice against Brugia pahangi infection were compared between both sexes, and the effects of testosterone on these eosinophil responses were examined. At the early phase of infection (7 to 10 days), female mice showed significantly higher peripheral eosinophil response than did males, and on day 5, 7 and 10 postinfection bone marrow eosinophil responses were also high in females. Live infective larvae but not dead ones could induce these differential responses of eosinophils between sexes. Castration of male mice increased the peripheral and bone marrow eosinophil responses to the levels of female mice, whereas castration of female mice did not affect these responses. Furthermore, testosterone treatment at a pharmacological dose in female mice suppressed peripheral and bone marrow eosinophil responses at the early phase of infection. These results suggest that the male sex hormone, testosterone, but not the female sex hormone has a role in the down-regulation of the systemic eosinophil responses of C57BL/6 mice to infection with B. pahangi. PMID- 1601642 TI - Tiopronin (2-mercaptopropionylglycine) has chemokinetic and chemotactic properties for polymorphonuclear leukocytes. AB - Tiopronin enhances migration of polymorphonuclear leukocytes (PMNs). The enhancing effect consists partly of a chemokinetic, and partly of a chemotactic effect. Intact sulfhydryl groups on the outer surface of the PMN plasma membrane are required for the enhanced locomotion: pretreatment of cells with the non penetrating sulfhydryl reagent (5,5'-dithiobis(2-nitrobenzoic acid) completely abolishes the activating effect of tiopronin, but has only a moderate effect on activation by fMet-Leu-Phe. Pretreatment of PMNs with pertussis toxin inhibits tiopronin-induced enhancement of migration, suggesting that a pertussis toxin sensitive G-protein is involved in the enhancing effect of tiopronin on PMN migration. PMID- 1601643 TI - Interleukin-6 can prime THP-1 macrophages for enhanced production of tumor necrosis factor-alpha in response to LPS. AB - Although interferon-gamma has been shown to effectively prime macrophages for enhanced production of tumor necrosis factor-alpha (TNF alpha), it is reasonable to assume that other cytokines present in the extracellular environment may likewise facilitate cytokine biosynthesis. For example, interleukin-6 (IL-6) is synthesized by synovial lining macrophages and fibroblasts, and has been detected (along with TNF alpha) in rheumatoid synovial effusions. Therefore, the purpose of the present study was to determine whether IL-6 influences the production of IL-1 beta and/or TNF alpha by THP-1 macrophages. Although IL-6 treatment alone resulted in only a slight increase in TNF alpha levels, administration of IL-6 followed by Sal. minnesota LPS resulted in a synergistic potentiation of TNF alpha production by THP-1 macrophages. The priming effect of IL-6 could be reversed by boiling, or by the addition of a neutralizing polyclonal antibody against IL-6. Notably, IL-6 only weakly enhanced interleukin-1 beta production. In summary, the ability of IL-6 to potentiate TNF alpha production by THP-1 macrophages may provide insight into the regulation of the cytokine network in inflammatory diseases, such as rheumatoid arthritis. PMID- 1601644 TI - Massive pulmonary embolism presenting as disseminated intravascular coagulation. AB - Disseminated intravascular coagulation (DIC) can be defined as evidence of activation of the coagulation mechanism resulting in proteolysis of fibrinogen by thrombin and plasmin and an acute thrombocytopenia. The association of pulmonary embolism (PE) with DIC has recently been reported but in reviewing recent textbooks of hematology, there is no mention of PE as a cause of DIC. Clinicians need to be made aware of this association since it affects the patient who is thought to be autoanticoagulated as well as the patient who has DIC of unknown cause. PE needs to be included in the differential diagnosis of an autoanticoagulated state and in DIC of unknown etiology. In both instances the recommended treatment is full-dose intravenous heparin therapy. PMID- 1601645 TI - Pectoralis major myocutaneous flap: analysis of complications in a VA population. AB - Forty-five cases of head and neck reconstruction with pectoralis major myocutaneous flaps (PMMF) between 1985 and 1990 were analyzed retrospectively for complications. Thirty-two cases were done at the VA Medical Center and 13 at Albany Medical Center, a private university hospital. Total complication rate was 58%. In the VA population, complication rate was 59% as compared to 54% at the Albany Medical Center, which appears statistically not significant. It has been suggested that VA populations tend to have poorer health and socioeconomic status and are more likely to have higher complication rates. This conjecture is not borne out by this study. Complications are described and compared. PMID- 1601646 TI - Recent results of oral cancer research in Kerala, India. AB - Findings from a research program in oral cancer at Regional Cancer Centre, Trivandrum, Kerala, India are reviewed. There is evidence of immune impairment in oral cancer patients. Plant lectins are being investigated for specific binding characteristics in various oral precancers and different histological subtypes of oral cancer. Tobacco and alcohol have been identified as the major risk factors for oral cancer. The chemopreventive potential of carotenoids and retinoids have been evaluated in oral leucoplakias. Beta-carotene and vitamin A in heavier doses induced remission of oral leukoplakias in 25%-50% of trial participants who continued with their tobacco and alcohol habits during the trial. The remission could be maintained with lower doses. Less than 20% of our patients with oral cancer were initially seen in localized stages. Various community-oriented programs for prevention of primary and secondary oral cancers are being evaluated. These include antitobacco health education, oral self-examination, and oral examination by trained volunteers. The results of radical radiotherapy and surgical salvage of radiation failure are also discussed. The 5-year disease-free survival rate of 34% is a reflection of the advanced stages of the disease when initially seen. Salvage rates with surgery for radiation failures were encouraging. PMID- 1601647 TI - Metastatic papillary cancer of the neck: a diagnostic dilemma. AB - The finding of papillary carcinoma in a neck mass usually leads to the presumptive diagnosis of metastatic thyroid carcinoma, with total thyroidectomy revealing the primary tumor. We report five cases of metastatic papillary carcinoma of the neck. The primary tumor in three of the cases was found to be nonthyroidal; two being discovered only after thyroidectomy failed to reveal a primary cancer. In the two thyroidal neoplasms, pathologic examination of the thyroid demonstrated only minimal tumor in one case and no detectable tumor in the other. These cases illustrate the pitfalls of diagnosis and treatment of these tumors and the utility of antithyroglobulin immunostaining in such cases. PMID- 1601648 TI - Histomorphometric analysis of intraoral split-thickness skin grafts. AB - Transposition of split-thickness skin grafts from the anterior thigh to the oral cavity is an ideal method for reconstruction of selected defects following major oncologic ablative surgery. This alternative potentially allows for tongue mobility, deglutition, and articulation superior to that obtained with bulky adynamic myocutaneous flaps. We have examined the adaptive responses of split thickness skin grafts to the intraoral environment with biopsies from 10 patients 11 to 90 months following oral cavity reconstruction. Histologic examination of intraoral skin grafts shows preservation of the cytoarchitecture of the epidermis, an absence or atrophy of skin appendages, and a statistically significant thinning of the keratin layer. A "junctional zone" between the normal oral cavity mucosa and the skin graft was identified. This zone is characterized by an abrupt transition from keratinized stratified squamous epithelium with a prominent granular layer, to nonkeratinized stratified squamous epithelium lacking a granular layer. This study clearly demonstrates that split-thickness skin, when transposed to the oral cavity, maintains the epidermal phenotype and does not assume the histologic characteristics of mucosa. PMID- 1601649 TI - Computed tomography of primary subglottic cancer: clinical importance of typical spread pattern. AB - The spread pattern of 14 cases of primary subglottic cancer, as seen on computed tomography (CT), is analyzed. Cricoid cartilage invasion was present in nine cases. Tracheal invasion was definite in four cases and questionable in three. Extralaryngeal soft tissue spread was present in nine cases; all but one had cartilage destruction. The patterns of spread seen accurately reflect reports in previous whole-organ section studies, and suggest that the elastic cone has a primary role in directing the spread of tumor. Anticipating spread to areas described above with CT and/or magnetic resonance imaging (MRI) can be used to try to improve treatment planning and perhaps outcome by: (1) avoiding placement of urgent tracheostomies close to the tumor; (2) helping to modify standard surgical approaches by suggesting lower-than-usual tracheostomies, or more extensive-than-usual thyroid gland resection; and (3) avoiding delay in diagnosis by strongly suggesting rebiopsy when imaging indicates a tumor is present, and initial endoscopy and biopsy cannot confirm the imaging findings. PMID- 1601650 TI - Resection of advanced cervical metastasis prior to definitive radiotherapy for primary squamous carcinomas of the upper aerodigestive tract. AB - Thirty-five previously untreated patients with stage IV squamous cell carcinoma of the upper aerodigestive tract with advanced neck disease (mass greater than 3 cm) but with primary lesions thought to be locally controllable with radiotherapy were selected between 1972 and 1988 for treatment by neck dissection followed by radiotherapy; postoperative to the neck and definitive to the primary. Limited neck dissections spared muscles, nerves, and vasculature structures unless clinically involved with cancer. All patients received at least 50 Gy, postoperatively, to the entire neck with doses of up to 75 Gy being delivered to the primary treatment portals. Regional (neck) failure occurred in 11% (4 of 35) patients. Overall, 5-year survival from cancer was 55%. Multiple levels of neck involvement were associated with poorer survival than a single large node; however, the difference was not statistically significant. Delay in the institution of radiotherapy following surgery adversely affected survival (p = 0.01). This study demonstrates that in selected patients it is possible to resect advanced nodal metastasis prior to treating the primary with radiotherapy without compromising cancer control. PMID- 1601651 TI - Branchio-oto-renal dysplasia associated with tetralogy of Fallot. AB - Branchio-oto-renal dysplasia in its full expression consists of external ear malformations, cervical fistulas or cysts, preauricular pits, hearing loss of conductive sensorineural or mixed type, and renal anomalies. The syndrome is inherited in an autosomal dominant mode. We present a sporadic case of BOR dysplasia associated with tetralogy of Fallot in a 30-month-old girl. The clinical aspects of the disease are discussed briefly. PMID- 1601652 TI - Streptococcal gangrene of the head and neck: a case report and review of the literature. AB - Necrotizing bacterial infections that occur in the head and neck are exceedingly rare and are often associated with a group A beta-hemolytic streptococcus (Streptococcus pyogenes). The disease is associated with soft tissue necrosis and vascular thrombosis. There appears to be an increasing incidence of hyperaggressive beta hemolytic streptococcal infections associated with high mortality rates. We report the survival of an otherwise healthy patient who developed a flu-like illness followed by a rapidly progressive toxic systemic illness associated with subtotal facial soft tissue necrosis down to bone. The recent literature related to this necrotizing bacterial infection is reviewed. Otolaryngologists must be aware of this entity since survival depends upon aggressive early wound management and high-dose intravenous antibiotics. PMID- 1601653 TI - Leiomyoblastoma of the larynx: report of a case. AB - Leiomyomas or benign tumors of smooth muscle origin are extremely rare in the larynx. A review of the literature revealed only 15 confirmed cases of leiomyoma, eight leiomyosarcomas, and no cases of leiomyoblastoma. An unusual case of "bizarre" laryngeal leiomyoma arising from the vocal cord, which is believed to be the first reported case in the literature is presented herein. PMID- 1601654 TI - Anatomy of the lateral pharyngotomy approach. AB - The pace of progress in head and neck surgery is rapid and can be bewildering to practitioners and students alike. As education is one of the major missions of Head & Neck, this new series is devoted to a comprehensive discussion of basic anatomical concepts manifested in the diagnosis, treatment, and care of patients with diseases of the head and neck. Although the anatomy of the head and neck region as related to surgical procedures will certainly be discussed, this will by no means be the only subject addressed. Other topics include the anatomic basis for specific pain syndromes encountered in patients with cancer of the head and neck, structural and lymphatic anatomy demonstrating patterns of disease spread, and constraints to standard surgical procedures because of anatomic "barriers." As medical illustration is an extremely important aspect of anatomy education, a concerted effort will be made to present material with illustrations that are understandable, clear, and concise. It is hoped that these subjects will not only educate but will also engender other topics of interest to readers. I welcome your suggestions for appropriate topics, as well as original contributions in keeping with the series guidelines. PMID- 1601655 TI - Pediatric functional endonasal sinus surgery: review of 210 cases. AB - Functional endonasal sinus surgery (FESS) is an effective treatment for chronic or recurrent sinusitis in children, most of whom have failed more conservative medical treatment. The endoscopes used in FESS allow direct visualization of the diseased tissue and restoration of physiologic mucociliary clearance, enabling the sinus mucosa to return to its normal condition after the procedure. For a period of 3 to 36 months, we followed the recovery of 210 children who underwent FESS between 1986 and 1989. The age range of the children at the time of the procedure was 14 months to 16 years. Eighty percent of these patients had improvement of their sinusitis. There were no major complications. Eight percent of the 210 children needed revision surgery. Pediatric FESS is a two-stage operation requiring follow-up nasal cleaning under general anesthesia. The most common findings during the second-stage endoscopy were adhesions and granulation formation. PMID- 1601656 TI - Carcinoma of the uvula and midline soft palate: indication for neck treatment. AB - According to common classification and staging systems, tumors of the uvula and soft palate are included in the group of oropharyngeal cancers. As such, the same staging systems apply and therapeutic decisions are made accordingly. Our experience with small tumors of the uvula and midline soft palate has shown that these common rules may not apply in these anatomical sites. A multicenter retrospective study was performed to examine the aspects of presentation and clinical course of tumors of the uvula. Only patients with small tumors, less than 2.0 cm in diameter, were included. Twenty-three cases were reviewed. Eleven (47.8%) patients had clinical or radiologic evidence of neck disease on presentation. Five of 12 (41.7%) patients who presented with negative neck were found eventually to have neck disease. Eight patients had cervical recurrence. Only one patient had local recurrence. We suggest that attention may need to be directed to the treatment of the neck of all tumors of the uvula and midline soft palate, regardless of size. PMID- 1601657 TI - A model for understanding benefit segmentation in preventive health care. AB - The marketing of traditional health care services, such as hospital and physician services, has matured with the integration of research from the medical sociology discipline and the marketing literature. In this article, we present a model to illustrate how an understanding of predispositions to health care behavior, integrated with benefit segmentation analysis, can contribute to more focused and effective marketing strategies for health-related products and services. PMID- 1601658 TI - Determinants of HMO success: the case of Complete Health. AB - The health maintenance organization (HMO) industry has experienced a variety of difficulties and criticisms in recent years. Various hybrid models have been proposed to alleviate these problems. This article presents an in-depth case study of factors associated with the success of one such hybrid: an individual practice association (IPA)-model HMO affiliated with an academic health center. The major success factors identified include the plan design/structure, the strategic orientation/practices, and the stakeholder management orientation practices. PMID- 1601659 TI - A cost-savings analysis of the use of a predictive instrument for coronary-care unit admission decisions. AB - The predictive instrument for acute ischemic heart disease is one of several clinical decision aids developed to reduce unnecessary coronary-care-unit (CCU) admissions. Previous cost analyses of such decision aids have been based on hospital charges; however, estimates based on hospital charges significantly overstate true cost savings to hospitals. The actual savings for a hospital that wants to implement the predictive instrument depend on the hospital's cost structure, the competitiveness of its medical care, and its payor mix. PMID- 1601660 TI - Multiple productivity measurement approaches for management. AB - Managers may desire an approach to combining multiple productivity measurements into one score. This article demonstrates two approaches to aggregating multiple measurements, data envelope analysis (DEA) and the Multicriteria Performance/Productivity Measurement Technique (MCP/PMT). These methods are applied to actual hospital materials management data and do not result in significantly different results. The productivity analysis must then be tempered according to managerial judgement. PMID- 1601661 TI - The Resource Management Initiative in the English National Health Service. AB - The Resource Management Initiative (RMI) is a policy thrust designed to more effectively utilize current expenditures in the United Kingdom's National Health Service by (1) integrating clinicians into management through a "clinical directorate," (2) establishing a closer external audit of the medical profession, and (3) implementing information systems. This article reviews the results from the first RMI sites and suggests a fit between the RMI effort and current programs in total quality management and continuous quality improvement. PMID- 1601662 TI - Developing interorganizational relationships in the health sector: a multicase study. AB - Because of the wide diversity among health care organizations, interorganizational relationships (IORs) among them are difficult to manage. This article describes three case studies that, taken together, suggest that IOR performance is related to IOR development processes. Specifically, IOR performance is related to the way managers process information to manage uncertainty and ambiguity. PMID- 1601663 TI - The urgency of care need and patient satisfaction at a hospital emergency department. AB - Satisfaction with the treatment and service at a hospital emergency department (ED) in a Swedish suburban area was generally high according to a questionnaire carried out among 758 patients with a 75 percent response rate. Satisfaction with the ED, however, was significantly lower among patients who were triaged nonurgent than among the immediate and urgent triage patients. This was especially true for younger patients. PMID- 1601664 TI - HCMR interview: Carolyn C. Roberts. Interview by Barbara P. McCool. AB - Carolyn C. Roberts--researcher, health care administrator, American Hospital Association board member--is a role model for women health care executives. As president of Copley Hospital in Morrisville, Vermont, Carolyn has provided national leadership on health care reform and the management of small and rural hospitals. Her creative and positive approach to life coupled with her sensitivity to serving patients and the community with quality service provides inspiration to many health administrators, physicians, and community leaders. The following interview is a tribute to a dear friend and a great lady. PMID- 1601665 TI - Missing roll pin from Beckman Spinchron centrifuge rotor. PMID- 1601666 TI - Use of Physio-Control Lifepak 8 defibrillator/monitors with optional QUIK-PACE pacing cassette. PMID- 1601667 TI - Comparison of neutral and cationic myocardial perfusion agents: characteristics of accumulation in cultured cells. AB - Uptake and washout kinetics of two new neutral lipophilic technetium-99m-labeled boronic acid adducts of technetium tris(dioxime) (BATO complexes) were studied in monolayers of contractile chick heart cells and compared to the cationic myocardial perfusion agents, 99mTc(CNCH2C(CH3)2OCH3)6+ (Tc-MIBI) and 201Tl+. 99mTcCl(CDOH)2(CDO)(BCH3), where CDO = cyclohexanedione dioxime (CDO-MeB), had a 7-fold greater net accumulation than Tc-MIBI and the most rapid unidirectional washout with a fast initial phase and a slower secondary component. Incubation with cationic membrane transport inhibitors or metabolic inhibitors had little or modest influence, respectively, on uptake of these BATO complexes. Studies with NIH 3T3 fibroblasts indicated that the neutral complexes did not show myocyte specific accumulation. PMID- 1601668 TI - Production of 6-[18F]fluoro-L-dopa and its metabolism in vivo--a critical review. AB - This report critically appraises methods for the synthesis of 6-[18F]fluoro-L-3,4 dihydroxyphenylalanine (6-FDOPA) that are based on labelling by non regioselective electrophilic fluorination, regioselective fluorodemetalation or nucleophilic substitution. Recommendations for the standardization of labelling procedures, the optimization of radiochemical yield and the assurance of product quality and safety are given. Studies of the metabolism of 6-FDOPA in vivo are also reviewed to emphasize the importance of the biochemical component of the development of this tracer for positron emission tomography (PET). PMID- 1601669 TI - The distribution of radioactivity in brains of rats given [N-methyl-11C]PK 11195 in vivo after induction of a cortical ischaemic lesion. AB - PK 11195 is a selective ligand for the peripheral-type benzodiazepine binding site (PTBBS). There are few such sites in normal brain but their number increases in association with tissue necrosis. The time-course of appearance of PTBBS around a focally induced ischaemic lesion in frontal cortex of rat brain was established by autoradiography using [N-methyl-3H]PK 11195. Using this information and the same experimental model of ischaemia, the distribution of radioactivity after injection of carbon-11 (t1/2 = 20.3 min, beta+ = 99.8%) labelled PK 11195 was studied. The purpose was to synthesize [N-methyl-11C]PK 11195 and to test its suitability as a tracer for depicting the presence of PTBBS in ischaemic lesions. The time-profiles of distribution of radioactivity in brain regions after intravenous injection of tracer and the ratio of radioactivity in lesioned compared with unlesioned cortex were determined. Data for the temporal (days after lesion induction) and for the regional retention of radioactivity were consistent with independent evidence (autoradiographic and immunohistochemical) for the occurrence of increased numbers of PTBBS, predominantly in association with macrophages, in areas undergoing necrosis. PMID- 1601670 TI - Synthesis, tissue distribution in rats and PET studies in baboon brain of no carrier-added [18F]RU 52461: in vivo evaluation as a brain glucocorticoid receptor radioligand. AB - 11,17 beta-Dihydroxy-6-methyl-17 alpha-(3-[18F]fluoro-prop-1- ynyl)androsta-1,4,6 trien-3-one [( 18F]RU 52461), an 18F-analog of RU 28362, was synthesized by bromide displacement with [18F]fluoride in 12-30% overall radiochemical yield (decay-corrected) within 140 min from end of bombardment (EOB). The specific activity was 900-1500 mCi/mumol (33.3-55.5 GBq/mumol) at the end of synthesis (EOS). Biodistribution studies indicated high adrenal and pituitary retention, and uniformly low uptake of [18F]RU 52461 in all other brain regions of the rat. Except for the pituitary, no specific receptor-mediated uptake of [18F]RU 52461 could be demonstrated using saturating doses of unlabeled RU 52461 in rat brain. While no change was observed throughout the brain areas in adrenalectomized rats and in animals coinjected with dexamethasone, when compared to controls. PET studies revealed extremely low levels of radioactivity in baboon brain. Therefore, [18F]RU 52461 does not appear to cross the blood-brain barrier, suggesting that this radiopharmaceutical is not suitable to visualize the brain glucocorticoid binding sites by PET. PMID- 1601671 TI - The use of 2-[18F]fluoro-2-deoxy-D-glucose as a potential in vitro agent for labelling human granulocytes for clinical studies by positron emission tomography. AB - In this study, 2-[18F]fluoro-2-deoxy-D-glucose, [( 18F]FDG) was used to radiolabel human granulocytes in vitro for possible clinical use by positron emission tomography (PET). Uptake of [18F]FDG was dependent on the amount of glucose in the labelling medium, e.g. when 1 x 10(7) granulocytes were incubated with [18F]FDG containing 15 micrograms/mL glucose 80% of [18F]FDG was incorporated within 30 min, but in the presence of 1 mg/mL of glucose it was reduced to 2%. Increasing the cell concentration and activating the granulocytes with Streptococcus pneumoniae, opsonized zymosan or phorbol myristate acetate all increased the uptake of [18F]FDG. Retention of the [18F]FDG by the cells as [18F]FDG-6-phosphate was also dependent on the extracellular glucose concentration, 9% was released within 60 min in the absence of glucose, but 27% in the presence of 1 mg/mL glucose. PMID- 1601672 TI - Synthesis of 18F-labeled fluconazole and positron emission tomography studies in rabbits. AB - [4-18F] 2-(2,4-difluorophenyl)-1,3-bis(1H-1,2,4-triazol-l-yl)-2-propanol [( 4 18F] fluconazole) was synthesized from its amino precursor. Fieldel-Crafts acylation of 3-fluoroacetanilide with chloroacetyl chloride produced 2'-fluoro-4' acteamido-2-(1H-1,2,4-triazole-1-yl) acetophenone in 12% yield. Sequential reaction with (1) dimethylsulphoxonium methylide and (2) 1,2,4-triazole followed by in situ hydrolysis resulted in 2-(2-fluoro-4-aminophenyl)-1,3-bis(1H-1,2,4 triazol-1-yl)-2-propan ol in 19% yield. A modified Schiemann reaction on this product resulted in [4-18F]fluconazole with a radiochemical yield of 1.0-2.0% (EOS) within 2 h. [4-18F]Fluconazole was used to measure the pharmacokinetics of fluconazole in rats by measurement of radioactivity in excised tissues and in rabbits by PET. In both species, there was rapid equilibration of [4 18F]fluconazole to a relatively uniform distribution of radioactivity in most organs. PMID- 1601673 TI - Simultaneous study of the biodistribution of radio-yttrium complexed with EDTMP and citrate ligands in tumour-bearing rats. AB - The influence of the ligands ethylenediaminetetramethylene phosphonic acid (EDTMP) and citrate (CIT) on the biodistribution of radio-yttrium in rats bearing a DS-carcinosarcoma was compared. 88Y-EDTMP and 87Y-CIT were i.v. injected into the same animals. Faster blood clearance and higher renal excretion were observed for the EDTMP-ligand. Of high practical interest is the reduced liver uptake of radio-yttrium (by one order of magnitude) with the EDTMP complex. Since bone and tumour accumulation is only weakly influenced, high tumour-to-liver ratios (up to 14) were observed. We propose to use EDTMP or similar complex ligands for liver blocking when radionuclides like 90Y, 169Yb, 225Ac or other group 3 elements are to be applied in endoradionuclide therapy technique. PMID- 1601674 TI - The evaluation of 186Re-labeled antibodies using N2S4 chelate in vitro and in vivo using tumor-bearing nude mice. AB - We have recently described a method for radiolabeling monoclonal antibodies, with metallic radionuclides using a new chelating agent N2S3. Using this chelate the monoclonal antibodies Lym-1 and B72.3 were labeled with 186Re and their biological integrity was evaluated in vitro and in vivo. 186Re-labeled antibodies using N2S4 methodology were found to be stable in human serum and retained their immunoreactivity. Intravenous administration of 0.5 mCi 186Re-labeled antibodies resulted in partial or complete regression of tumor tissue in mice. PMID- 1601675 TI - Amino acids for the measurement of protein synthesis in vivo by PET. AB - In principle, PET in combination with amino acids labelled with positron-emitting radionuclides and kinetic metabolic models, can quantify local protein synthesis rates in tissue in vivo. These PET measurements have clinical potential in, for example, oncology, neurology and psychiatry. An optimal positron-emitting amino acid for the measurement of PSR has a high protein incorporation, can easily be prepared by automated equipment and has minimal non-protein radioactive metabolites. Presently L-[methyl-11C]methionine, L-[1-11C]leucine, L-[1 11C]tyrosine, L-[1-11C]phenylalanine, L-[1-11C]methionine and L-[2 18F]fluorotyrosine are under evaluation in normal volunteers and/or in patients. Several other amino acids are suggested. No comparison of the clinical usefulness of the different amino acids in man is yet available. Because of the longer half life of 18F compared to 11C, [18F]fluoro amino acids may have advantages over [11C]amino acids for the investigation of tissue with relative slow protein synthesis, such as brain, and for application in institutions with an off site, but nearby cyclotron. The half life of [13N]amino acids is considered to be too short for flexible clinical application. As yet no metabolic compartmental model has been investigated for [13N]amino acids. For routine application reliable preparation of the radiopharmaceutical is essential. Of all the amino acids under evaluation, a reliable, high yield, easy to automate production procedure is available for L-[methyl-11C]methionine only. It is however unlikely that this tracer can accurately measure PSR because of its non-protein metabolism. For the other amino acids the main problems in production are associated with complex multistep syntheses and/or low radiochemical yields, complex purification methods and the need to isolate the L-enantiomer. The kinetic metabolic models under investigation, consist of 4 or 5 compartments depending on the necessity to compensate for labelled metabolites. The metabolic profile of the amino acids is mainly extracted from animal experiments. Because of the number and amount of labelled metabolites in plasma, [11C]carboxylic labelled amino acids are preferred to amino acids with carbon-11 in another position. As yet no recommendation can be given on the optimal labelled amino acid(s) for PSR measurement in vivo nor on the methods to prepare the amino acids reported for this purpose. PMID- 1601676 TI - Investigations of N-linked macrocycles for 111In and 90Y labeling of proteins. AB - To simplify the synthesis of macrocyclic chelators, commercially available macrocyclic amines were condensed with halogenated acetic acid to prepare the five chelators 12N4 (DOTA), 14N4 (TETA), 15N4, 9N3 and 12N3. Only 12N4 and 9N3 showed efficient labeling of the free chelator with 111In and 90Y. Serum stability studies at 37 degrees C with In-labeled DTPA, 12N4 and 9N3 showed no loss of label over 2 days whereas, with 90Y, only 12N4 showed stabilities comparable to DTPA. The 12N4 chelator was derivatized by attaching biotin on one N-acetate group to stimulate the attachment to protein. The serum stability for both 111In and 90Y was identical to that of biotin derivatized DTPA and lower than that of the free chelators. Biodistribution studies in normal mice of a model protein (avidin) labeled with 90Y via biotinylated 12N4 and biotinylated DTPA showed identical distribution at 1 day except in bone where the %ID/g for the macrocyclic-conjugated protein (3.4 +/- 0.5, N = 8) was significantly (P less than 0.001) lower than that of the DTPA-conjugated protein (9.4 +/- 0.9, N = 7). In conclusion, macrocycles may be readily synthesized from the macrocyclic amines and several show useful stabilities with In and Y. When N-linked to a protein, the Y biodistribution was found to be superior to that of the corresponding DTPA coupled protein. PMID- 1601677 TI - In vivo quantification of cholesterol content in human carotid arteries by quantitative gamma-camera imaging after injection of autologous low density lipoproteins (LDL). AB - Low density lipoproteins (LDL) were isolated by immunoaffinity chromatography from 18 patients (31-70 years) suffering from primary hypercholesterolemia with angiographically proven atherosclerosis of either one or both carotid arteries. LDL were labeled with 123I (1 mCi/mg LDL) by the iodine monochloride method followed by purification with dialysis and immediately reinjected thereafter. Gamma-camera serial controls over carotid regions allowed visual detection of uptake of the radiocompound uptake in 12 out of the 18 patients. The lipid entry ratio (LER; counts over the vascular region/pixel as compared to the contralateral side after background subtraction) confirmed the visual findings. Whole body images performed until 20 h after reinjection showed 3 different kinetic types of LDL-influx into the vessel wall: decreasing (type I), increasing and then decreasing (type II) and continuously increasing (type III) with time. Four patients underwent endarterectomy within 2-7 weeks after gamma-camera imaging. Histological control revealed an extensive amount of "foam cells" in tissue samples derived during surgery and an absence of endothelial lining in samples belonging to patients with type II kinetics. PMID- 1601678 TI - [Changes in transitory evoked otoacoustic emissions in chemotherapy with cisplatin and 5FU]. AB - The aim of this study was to detect changes of transient evoked otoacoustic emissions (TEOAE) during chemotherapy with cisplatin and fluorouracil (5FU). A review of the literature reveals that the incidence of cisplatin ototoxicity varies from 9% to 50%; this variation is due to differences in doses, duration of administration, to the criteria for ototoxicity and on audiological methods. Three cycles of chemotherapy (1000 mg/m2 5FU from day 1 to 5 and 100 mg/m2 cisplatin on day 1) were given to 12 patients; the OAE were measured before chemotherapy and after each administration. In 86% of the ears measured we found changes in the TEOAE; the mean values for the amplitude of the TEOAE decreased about 13% after the end of the chemotherapy. Pure tone thresholds were reduced in almost 50% of the measured ears. The decrease of amplitude of TEOAE is an early sign of an ototoxic secondary effect, probably due to damage to the outer hair cells. TEOAE is a sensitive method for detecting ototoxicity in cisplatin-treated patients and more reliable than pure-tone audiometry or evoked acoustic potentials. PMID- 1601679 TI - [Follow-up of sound pressure level at the tympanic membrane at varying impedance of the tympanic membrane-ossicular system]. AB - We investigated the influence of varying compliance of the tympanic membrane on the sound pressure level of the human ear canal using a model with adjustable compliance. Decrease of compliance augments the sound pressure close to the tympanic membrane due to the increase of reflected sound pressure. This augmentation occurs in a narrow frequency area near the maximum resonance frequency and reaches 6 dB (SPL). These experimental data correlate well with clinical investigations in patients with middle ear effusion before and after operation and in patients performing the Valsalva manoeuvre. PMID- 1601680 TI - [Intraoperative monitoring with transtympanic electrocochleography]. AB - Transtympanic electrocochleography (ECoG) enables auditory evoked potentials to be recorded directly from the peripheral organ, and ECoG recordings can be used as a routine during operations. Examples of cochlear and eighth nerve monitoring in middle ear, inner ear, and cerebellopontine angle surgery are given. This monitoring tool provides a continuous feedback to the surgeon of the effects of the operation on the cochlea and the auditory pathway. PMID- 1601681 TI - [Value of Papanicolaou exfoliative cytology in diagnosis of cancers of the upper aerodigestive tract]. AB - Exfoliative cytology of the pharynx and larynx is a valid tool in the diagnosis of tumours. It is useful in the follow-up of chronic epithelial lesions of these regions and after tumour therapy. Cytological findings in group "Pap III" demand careful follow-up possibly with biopsy. For all other groups a biopsy is only indicated if there is a strong clinical suspicion of a tumour in the individual case. The simple technique of exfoliative cytology makes it an important part of aftercare of patients with malignancy, especially squamous cell carcinoma of the pharynx and larynx. The validity of the method depends on the care with which the specimen is taken and on the experience of the investigator. PMID- 1601682 TI - [Examination technique in ultrasound calculus detection in the submandibular gland]. AB - Techniques such as orthopantomography and ultrasound are usually employed for examination for submandibular calculi, but we have found transverse scanning of the submandibular gland by ultrasound to be safe and rapid. As the mandible and hyoid bone present a shadow there is a margin for possible error, but this technique enables these areas to be seen and thus checked: a submandibular calculus may be seen as a third shadow between the other two. Comparison showed ultrasound to be superior to orthopantomography. If the ultrasound is negative and there is a strong clinical suspicion of a submandibular calculus orthopantomography is the next step to be employed. PMID- 1601683 TI - [Differential diagnosis of an ear canal polyp]. AB - Aural polyps or granulation tissue, though usually due to infection, may represent a neoplasm, the most frequent malignant tumour in childhood being rhabdomyosarcoma. We report a 9-year-old boy from whom an aural polyp was removed 4 years ago, with the histological diagnosis of a botryoid (alveolar type) rhabdomyosarcoma. Surgery and chemotherapy with cyclophosphamide, vincristine, adriamycin and actinomycin D were followed by a local recurrence 2 years later. This was treated by chemotherapy and irradiation with 50 Gy; the child has now been free of disease for 2 years. Rhabdomyosarcoma of the ear has a considerably improved cure rate with newer treatments if the diagnosis is made early by biopsy. PMID- 1601684 TI - 'Loopholes' weaken hospital accreditation policy. PMID- 1601685 TI - AIDS cases surpass 200,000. PMID- 1601686 TI - HIV infection soars in DC women. PMID- 1601687 TI - 'Ad Diction Ary' of drug users' terms. AB - Physicians obtain information by verbally communicating with patients. But communication is frequently impaired for varied reasons. Often, physicians and patients speak different languages, even when both use English as their vernacular. Intravenous drug users have their own way of referring to their lifestyle and habits. Without understanding the terms they use, the physician will have difficulty appreciating the course of events leading up to a disease. Terms unique to the drug culture, or terms that have a different meaning to drug users than they do to the general public are defined herein. This special lexicon is the culmination of the author's 5-year file-card collection of terms. PMID- 1601688 TI - Office diagnosis of lower extremity venous insufficiency and treatment with the use of nonprescription support hose. AB - A two-part crossover study assessed the efficacy of nonprescription support pantyhose by evaluating the relative performance of sheer- versus firm-support types in 30 women with lower extremity complaints. In this clinical trial, 23 women wore nonprescription firm-support pantyhose and seven wore sheer-support pantyhose during the initial 4-week treatment period. Next, treatment was discontinued for 2 weeks, after which a 4-week crossover trial was started. During the crossover, the 23 women who had worn the firm-support hose during the initial trial wore the sheer-support hose, and the seven who had worn the sheer support hose switched to wearing the firm-support hose. The 2-week washout period did not prove sufficient to allow measured values to return to baseline, thus invalidating the crossover comparisons between the sheer- and firm-support pantyhose. However, the direct comparison of results showed that patients generally experienced an improvement in venous circulation by using either firm- or sheer-support hose as evaluated by venous index measurements and a corresponding decrease in subjective complaints. One year after this study was completed, the patients were recalled. Of the 25 who were seen at this follow-up, 91% continued to use support hose, either when they had symptoms or on a regular daily basis. Venous circulation, as evaluated by noninvasive Doppler ultrasound and photoplethysmography, remained improved. PMID- 1601689 TI - Laterally transposed pelvis: a new and proper name for an old problem. AB - There is need for specific terminology for osteopathic findings, including the findings in postural examination. A static test for laterally transposed pelvis is sometimes critical to the establishment of a diagnosis of postural imbalance, particularly in the minor forms of this important clinical entity. There is need for a word or phrase that identifies this clinical finding and nothing else. The phrase laterally transposed pelvis is nominated to indicate a specific finding in the static evaluation of pelvic position in the frontal (coronal) plane in relation to the vertical extension of the midheel line (sagittal plane). The definition of laterally transposed pelvis is: With the patient standing, knees fully extended bilaterally and the feet together on a flat horizontal surface, the median (midsagittal) plane of the pelvis is observed to lie laterally to the vertically extended midheel line (median/midsagittal plane). PMID- 1601690 TI - Patient's rights and doctor's rights: HIV-infected physicians and dentists on the cut edge. AB - Media, professional associations, public health agencies, legislators, and courts have focused attention to the problem of HIV-infected healthcare professionals. Practitioners should become aware of recently revised ethical guidelines, the doctrine of informed consent, court decisions, and legislation because of the effects these events have on practice and because patients will pose questions on these issues. PMID- 1601691 TI - Human immunodeficiency virus testing: update. AB - Human immunodeficiency virus (HIV) types 1 and 2 have been associated with the acquired immunodeficiency syndrome (AIDS). The detection of HIV infections is based on the screening of serum samples for the presence of antibodies to HIV proteins. Serum samples that test positive on screening must be assayed by a confirmatory test to provide a definitive report on the presence of HIV infection. This article reviews the currently available screening and confirmatory testing procedures and their limitations. PMID- 1601692 TI - Simple guidelines for HIV testing in the physician's practice. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1601693 TI - Intern orientation: obstacle or opportunity? AB - Orientation programs for medical interns generally bombard new physicians with a barrage of information from the hospital director of medical education, the chief executive officer, and other hospital personnel, as well as from a number of outside speakers. Advanced cardiac life-support training and social events round out the orientation program, which typically lasts 3 to 4 days. The authors propose a three-phase orientation program that begins even before the intern reports for duty and continues for an estimated 6-month period thereafter. This seemingly long-term time investment will foster good relations between employer and employee, thereby helping to encourage the intern to stay on as a resident and staff physician. Such commitment can only enhance the growth of the osteopathic medical education programs. PMID- 1601695 TI - New strategies for the acquired immunodeficiency syndrome (AIDS) PMID- 1601694 TI - Spinal-anesthesia-induced hypotension study challenged. PMID- 1601696 TI - Parietal bone mobility in the anesthetized cat. AB - To quantify parietal bone motion in reference to the medial sagittal suture, a newly developed instrument was attached to the surgically exposed skull of anesthetized adult cats. The instrument differentiated between lateral and rotational parietal bone movements around the fulcrum of the suture. Bone movement was produced by external forces applied to the skull and by changes in intracranial pressure associated with induced hypercapnia, intravenous injections of norepinephrine, and controlled injections of artificial cerebrospinal fluid into the lateral cerebral ventricle. Responses varied considerably among test animals. Generally, lateral head compression caused sagittal suture closure, small inward rotation of the parietal bones, increased intraventricular pressure, transient apnea, and unstable systemic arterial blood pressure. Graded increases in intracranial volume produced stepped increases in pressure, lateral expansion at the sagittal suture, and outward rotation of the parietal bones. We attribute variations in animal response largely to differences in intracranial and suture compliance among them. Cranial suture compliance may be an important factor in defining total cranial compliance. PMID- 1601698 TI - The varied clinical presentations of meningococcal infection. AB - The clinical presentation of Neisseria meningitidis may include bacteremia, septic shock, or meningitis. The polysaccharide capsule of the organism appears to be the major determinant and is necessary for specific immunity. Colonization of the nasopharynx is required for invasion, and persons with complement component deficiencies are particularly at risk of infection. The organism can be detected by culture of blood or spinal fluid, or by antigen detection in spinal fluid. Prompt therapy with penicillin G is necessary for a good outcome. The occurrence of secondary cases requires that prophylactic therapy be administered to close contacts of index cases. The cases presented herein illustrate a variety of manifestations of meningococcal infection, and all of the patients initially were seen in primary care settings. It is important for physicians to be vigilant for these infections so that appropriate therapy may be instituted rapidly. PMID- 1601697 TI - Physiologic role and clinical significance of reverse cholesterol transport. AB - Low levels of high-density lipoproteins have been consistently shown to be a major risk factor for coronary heart disease. However, the precise role of HDL in the prevention or reversal of atherosclerosis (or both) is unknown. It has been proposed that HDL functions jointly with the enzyme lecithin:cholesterol acyltransferase and the cholesteryl ester transfer protein to facilitate the movement of cholesterol from tissues to the liver. This mechanism--referred to as reverse cholesterol transport--has been shown to be an important physiologic mechanism. However, its clinical significance, though intriguing, is unclear. This article reviews recent advances concerning the components of reverse cholesterol transport and evaluates their potential significance in the early diagnosis and treatment of atherosclerosis. PMID- 1601699 TI - Autologous blood transfusion: standard of care for the 1990s. AB - The risks of transmission of devastating and sometimes fatal viral infections from homologous blood transfusion have caused concern among patients undergoing elective major surgical procedures. Autologous blood transfusions eliminate the potential risk posed by these viruses. A well-informed primary care physician can help patients undergoing elective surgical procedures to determine whether autologous blood transfusion is an appropriate therapeutic alternative. A well equipped and certified blood bank will allow patients to donate autologous units while keeping patient risk at a minimum. PMID- 1601701 TI - Training osteopathic medical students in behavioral medicine and psychiatry. AB - Medical students need more comprehensive training in behavioral sciences to cope with the increasing acuity of patients seen in an ambulatory-care setting. Present-day psychiatry teaching and clinical rotations emphasize severe psychopathologic disorders and inpatient care. Colleges of osteopathic medicine should integrate behavioral sciences into the preclinical curriculum and clinical training. Clinical psychiatry training should prepare students to care for patients with the kinds of behavioral difficulties seen in primary care settings in an integrated manner. PMID- 1601700 TI - Helping patients to reduce their risk of acquiring sexually transmitted disease. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1601702 TI - Recruiting interns and residents to an osteopathic medical training program. AB - As more graduates of colleges of osteopathic medicine enroll in allopathic training programs and specialty programs, medical directors of osteopathic medical institutions are faced with the challenge of maintaining a well-trained housestaff. More important, perhaps, this exodus threatens the very core of osteopathic medicine, namely, its ability to produce well-trained primary care physicians. A recruitment plan used at the Chicago College of Osteopathic Medicine and its affiliates is presented here. The plan emphasizes the importance of trainee involvement in their own education as well as the use of residents in recruiting interns and specialty residents. PMID- 1601703 TI - A large accumulation of metallic foreign bodies in the stomach. AB - A routine x-ray examination showed a fishhook lodged in the esophagus of an asymptomatic 68-year-old man. Further examination revealed multiple foreign objects in his stomach. In all, 82 metallic objects were removed endoscopically. The authors believe that this is the largest accumulation of foreign objects to be removed by this procedure and that endoscopy, properly performed, is a safe and effective alternative to laparotomy. However, surgery remains a safer procedure in some situations. PMID- 1601705 TI - Comments on modified tracking curricula. PMID- 1601706 TI - Under the influence. Students search for sobering solution to substance abuse. PMID- 1601704 TI - Splenic cyst. AB - The authors describe a patient who had a benign, secondary splenic cyst definitively diagnosed preoperatively by use of a computed tomography scan. Because it was not possible to distinguish between a primary and secondary nonparasitic cyst preoperatively, the treatment of choice was elective splenectomy. This procedure allows confirmation of the clinical diagnosis and involves low morbidity and mortality. PMID- 1601707 TI - Food safety paramount in '90s. PMID- 1601708 TI - Hammer time--veterinary profession no longer on defense concerning food safety. PMID- 1601709 TI - Konyha receives Presidential Rank Award. PMID- 1601710 TI - From Boston to the Los Angeles County milk shed. PMID- 1601711 TI - Who regulates the practice of veterinary medicine? PMID- 1601712 TI - Prevalence of the 14/20 centric fusion chromosomal aberration in US Simmental cattle. AB - Cytogenetic evaluation was made on 353 Simmental cattle (166 male, 187 female) from 113 herds in 26 states. One hundred thirty-eight (39%) were found to be heterozygous-positive for the 14/20 centric fusion chromosomal translocation, including 41 (25%) males and 97 (52%) females. One submitted heparinized blood sample from a Simbrah bull was found to be positive for 14/20 and 1/29 centric fusions. Sampling, which was based on requests, was highly selective. Thus, the 39% prevalence found was not representative of 14/20 centric fusion in the national Simmental breed. On the basis of our findings, cytogenetic evaluation of breeding stock was consistent with modern management practice. PMID- 1601713 TI - ECG of the month. PMID- 1601714 TI - Evaluation of selected plants for their toxic effects in canaries. AB - Leaves or fruit from 14 plants considered to be toxic to pet birds were administered by gavage to 15 pairs of canaries (Serinus canaria). Each bird was given 0.12 to 0.70 g of plant material. One pair served as a control and was given distilled water. The plant materials were flash-frozen in liquid nitrogen, pulverized, and resuspended in deionized water for administration. Of the plants tested, 5 (oleander, lupine, foxglove, yew leaves, and dieffenbachia) were considered highly toxic and were associated with acute death of birds. The remaining plant samples caused no, or only transient, clinical illness. PMID- 1601715 TI - Effects of antibiotic prophylaxis on postoperative complications after rumenotomy in cattle. AB - A single preoperative dose of antibiotic proved as effective as a preoperative and 7-day postoperative course in reducing complications following rumenotomy in cattle. Exploratory rumenotomy was performed on 29 healthy Angus steers, which were allotted to the following treatment groups: (1) no antibiotic therapy, (2) single-dose, preoperative, antibiotic prophylaxis, using potassium penicillin G, and (3) preoperative potassium penicillin G prophylaxis, followed by a 7-day postoperative course of procaine penicillin G. Steers receiving antibiotics had significantly greater postoperative feed intake, lower rectal temperatures, and fewer abscesses at the surgical site than those receiving no antibiotics. There was no significant difference between animals receiving a single preoperative dose of antibiotic and those treated for an additional 7 days after surgery. In human medicine, it is generally agreed that a single preoperative dose of antibiotic offers effective prophylaxis. There are few published reports on antimicrobial prophylaxis in the veterinary literature, particularly in regard to large animals. Considering USDA requirements for milk withholding times and withdrawal times prior to slaughter for food animals receiving antibiotics, the findings of this study have medical as well as economic value. PMID- 1601716 TI - Comparison of endometrium before and after repair of third-degree rectovestibular lacerations in mares. AB - The endometrial response of mares to repair of third-degree rectovestibular lacerations was evaluated. Endometrial biopsy specimens from 8 mares with third degree rectovestibular laceration were obtained immediately before surgery and from 9 to 15 days after repair. Presurgical endometrial biopsy specimens were classified as category I for 2 mares; category II, attributable to slight endometritis, for 5 mares; and category III, attributable to moderate-to-severe endometritis, for 1 mare. Within 15 days after rectovestibular repair, all endometrial biopsy specimens were classified as category I. Results indicated that mares with third-degree rectovestibular injuries are candidates for breeding by artificial insemination by 2 weeks after repair of the injury. PMID- 1601718 TI - Hypoprothrombinemia secondary to administration of sulfaquinoxaline to dogs in a kennel setting. AB - Sulfaquinoxaline, a coccidiostat readily available to the public, was mixed in the drinking water for this purpose by the owner. Secondary to its use, a bleeding disorder attributable to hypoprothrombinemia developed in several dogs. Clinical signs of bleeding ceased 24 hours after institution of vitamin K1 and discontinuation of sulfaquinoxaline in the drinking water. This report should remind veterinarians that drugs and medications readily available to the public may have adverse effects in animals, and such problems should be investigated whenever multiple dogs in a common setting are affected with the same clinical problem. PMID- 1601717 TI - Relation between pharmacokinetics of amikacin sulfate and sepsis score in clinically normal and hospitalized neonatal foals. AB - Pharmacokinetic values after IV administration of amikacin sulfate were determined for clinically normal and hospitalized foals during the first week of life. The relations between drug disposition and sepsis score and serum creatinine concentration also were studied. In clinically normal foals, differences in sepsis score, serum creatinine concentration, and pharmacokinetic variables of amikacin were not found between foals 1 to 3 and 4 to 7 days old. In hospitalized foals, sepsis score, serum creatinine concentration, area under the curve, area under the moment curve, and mean residence time were greater, and total clearance was decreased, compared with values in clinically normal foals. Sepsis score and serum creatinine concentration were inversely correlated to amikacin clearance and appeared to be useful indicators of altered drug disposition. PMID- 1601719 TI - Bone marrow hypoplasia in a feminized dog with an interstitial cell tumor. AB - Bone marrow hypoplasia and feminization developed in a 10-year-old male German Shepherd Dog with interstitial cell tumor. Clinical abnormalities included pyrexia, pale mucous membranes, signs of abdominal pain, large left testis, atrophied right testis, and feminization. Abnormal laboratory findings included pancytopenia, bacteremia, bacteriuria, and pyuria. Results of cytologic examination of a bone marrow aspirate were consistent with aplastic anemia. Serum estradiol concentration was high, and serum testosterone concentration was low, compared with normal values for male dogs. The left testicular mass was identified as an interstitial cell tumor. Other causes of the aplastic anemia or feminization were not found. PMID- 1601720 TI - Rectal hemorrhage associated with vascular ectasia in a young dog. AB - Rectal bleeding in a 7-month-old 13-kg sexually intact female mixed-breed dog was determined to be associated with vascular ectasia of the small intestine, descending colon, rectum, and anus. Microscopically, the telangiectasia was associated with lymphangiectasia and focal ulceration. Surgical intervention resulted in incomplete resection of the lesion and only temporary amelioration of clinical signs. The dog's age was compatible with a congenital origin for the defect, but an acquired cause could not be excluded. PMID- 1601721 TI - Results of continuous ambulatory electrocardiography in a cat with hypertrophic cardiomyopathy. AB - An 8-year-old neutered male cat with a history of intermittent collapse and dyspnea was evaluated. Hypertrophic cardiomyopathy was diagnosed on the basis of findings from physical examination, radiography, and echocardiography. Cardiac arrhythmias were not recorded during routine electrocardiography. Continuous ambulatory electrocardiography documented severe ventricular arrhythmias (ventricular premature complexes, ventricular bigeminy, and paroxysmal ventricular tachycardia). Continuous ambulatory electrocardiography can detect intermittent and potentially life-threatening cardiac arrhythmias. PMID- 1601722 TI - Ventricular septal defects in bovine twins. AB - Ventricular septal defects were diagnosed in twin cows. One of the cows was slaughtered, and the other died of complications associated with the defect. This and other reports may provide evidence to determine the basis of ventricular septal defects in cattle. PMID- 1601723 TI - Manually assisted ejaculation in a stallion with erectile dysfunction subsequent to paraphimosis. AB - A Thoroughbred stallion with erectile dysfunction following paraphimosis was managed to allow consistent ejaculation. Ejaculation was elicited in this stallion by applying manual stimulation to the base of the penis. This technique allowed consistent ejaculation, and the stallion was able to return to natural service. Historically, stallions with this degree of penile dysfunction have been considered incapable of ejaculation and unable to continue as breeding animals. PMID- 1601724 TI - Pulsed spectral Doppler evaluation of a peripheral arteriovenous fistula in a horse. AB - Pulsed spectral Doppler ultrasonography was used to characterize the vascular involvement and anatomic boundaries of a peripheral arteriovenous fistula on the hemithorax of a horse. This information facilitated surgical removal of the fistula. Pulsed spectral Doppler evaluation of suspected peripheral vascular anomalies should be considered for the diagnosis of similar lesions, in which contrast angiography is not possible. PMID- 1601725 TI - Gastric leiomyosarcoma in a horse. AB - Gastric leiomyosarcoma was diagnosed in a 12-year-old Thoroughbred gelding. The horse was examined because of anorexia, weight loss, and intermittent fever of 1.5 months' duration. Antemortem diagnostic testing was extensive, but a definitive diagnosis could not be reached with noninvasive methods. Exploratory celiotomy confirmed an intra-abdominal mass, and the horse was euthanatized. Necropsy revealed a firm mass associated with the distal portion of the esophagus, cranial two thirds of the stomach, and visceral surface of the liver. The histopathologic diagnosis was leiomyosarcoma. PMID- 1601726 TI - Loop colostomy for management of rectal tears and small-colon injuries in horses: 10 cases (1976-1989). AB - Loop colostomy was performed in 10 horses as treatment for grade-III rectal tears (n = 6 horses), small-colon infarction (n = 2 horses), perirectal abscess and stenosis (n = 1 horse), and small-colon stricture (n = 1 horse). In 7 horses, the colostomy was constructed through a single incision low in the left flank, with closure of the incision around the stoma (single-incision technique). In 3 horses, 2 of which had colostomy performed as a standing procedure, the selected segment of small colon was placed from a flank incision into a separate, small incision low in the left flank (double-incision technique). Five horses underwent colostomy reversal (at 18 to 63 days) and 2 of these horses, both with grade-III rectal tears, recovered completely. Of 8 horses that did not survive, 6 died from the primary disease or associated complications. Technical problems associated with colostomy accounted for death of 2 horses. One horse had gastric rupture attributable to suture occlusion of the small intestine after colostomy reversal, and another horse had complications of incisional infection after repair of a peristomal hernia. Small-colon prolapse through the stoma necessitated premature reversal of the colostomy in a horse that was euthanatized because of worsening laminitis. Minor complications of the colostomy procedure were partial stomal dehiscence (n = 4 horses), partial dehiscence of the flank wound after colostomy reversal (n = 2 horses), and small ventral midline hernia after colostomy reversal (n = 1 horse). Loop colostomy may be of benefit to horses with rectal tears, provided it is done soon after the tear occurs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601727 TI - Intramedullary pinning of femoral diaphyseal fractures in neonatal calves: 12 cases (1980-1990). AB - Medical records of 12 calves less than or equal to 1 month old, with fracture of the femoral diaphysis, were reviewed. Ten calves were within 1 week of birth at the time of diagnosis. Open reduction was accomplished by use of a lateral approach. Retrograde intramedullary pinning was accomplished in all calves, using 2 (n = 4 calves) or 3 (n = 8 calves) pins. Cerclage wire was used to supplement fixation in 7 calves. A closed continuous suction drain was placed along the lateral aspect of the femur in every calf. Postsurgical complications included seroma formation over the middle gluteal musculature (n = 5 calves), pin migration (n = 6 calves), and osteomyelitis (n = 1 calf). Pin migration was observed in 4 calves that had been treated with nonthreaded trochar point pins. Fractures in 10 of 12 calves (83%) were considered to have healed satisfactorily. One calf was euthanatized because of septic osteomyelitis of the femur. One calf was euthanatized because of persistent lameness and pin migration. Pins were removed in 8 of 12 calves (67%) between the 13th and 90th postoperative days. Results of this study indicate that application of intramedullary pins may be a useful solution for management of femoral diaphyseal fracture in young calves. PMID- 1601728 TI - Plasma cell stomatitis-pharyngitis in cats: 40 cases (1973-1991). AB - Clinical signs, laboratory findings, and treatment results of 40 cats with the histologic diagnosis of plasma cell stomatitis-pharyngitis are discussed. Median age was 7.1 years, with no discernable sex predilection. Anorexia and difficulty prehending food were the most common clinical signs. Hyperproteinemia with associated hyperglobulinemia was the most common laboratory finding. Of various treatments, administration of corticosteroids or injectable gold (aurothioglucose) proved most effective in controlling the clinical signs. PMID- 1601729 TI - Complications associated with the use of iohexol for myelography of the cervical vertebral column in dogs: 66 cases (1988-1990). AB - Medical records of 66 dogs that had undergone myelography, using iohexol (240 mg of iodine/ml, 0.3 to 0.5 ml/kg of body weight) during a 2-year period, were reviewed. In 3 dogs, myelography was performed twice during different anesthetic procedures. Neurologic abnormalities were more pronounced the day after myelography in dogs with caudal cervical spondylomyelopathy (P less than 0.01), meningitis (P less than 0.01), or extradural tumors (P less than 0.05). Neither anesthetic regimen nor duration of anesthesia significantly affected the frequency of complications. Seizures occurred after myelography in 6 dogs, and 1 dog had seizures after each of 2 myelographic procedures. The frequency of seizures was significantly greater in male Doberman Pinschers afflicted with caudal cervical spondylomyelopathy. Male dogs (P less than 0.01) and Doberman Pinschers (P less than 0.001) had higher prevalence of seizures. Caudal cervical spondylomyelopathy was associated with higher prevalence of seizures, compared with all other diagnoses (P less than 0.001). Seizures were significantly more prevalent when body weight was greater than or equal to 29 kg (P less than 0.001), when greater than or equal to 2 injections of contrast medium were administered (P less than 0.016), or when 2 injections of contrast medium were given at the cisterna magna (P less than 0.015). The 10% prevalence of seizures after myelography with iohexol in the study reported here is greater than in previous reports, but is lower than that reported after myelography using metrizamide. PMID- 1601730 TI - Arboviral encephalomyelitides of livestock in the western hemisphere. PMID- 1601731 TI - What is your diagnosis? Left-sided heart failure attributable to chronic vegetative endocarditis of the mitral and aortic valves. PMID- 1601732 TI - Rethinking the promotion and tenure process: a response to Hiller and Ritvo. PMID- 1601733 TI - The 1991 Mary E. Switzer Lecture: racing ahead of her time--the legacy of Mary E. Switzer. PMID- 1601734 TI - Perspectives on quality service management in health care. PMID- 1601735 TI - The federal role in allied health workforce data. PMID- 1601736 TI - Unification of academic and clinical departments in academic health sciences centers. PMID- 1601737 TI - Unification of academic and clinical departments in academic health sciences centers: an alternative view. PMID- 1601738 TI - 24th annual Presidential Address to the Association of Schools of Allied Health Professions. PMID- 1601739 TI - Computer tracking of germ cells in the cycle of the seminiferous epithelium and prediction of changes in cycle duration in animals commonly used in reproductive biology and toxicology. AB - A computer program called Stages was written to aid the tracking of germ cells and stages forward and backward through time in the cycle of the seminiferous epithelium. The program incorporates the basic kinetics of spermatogenesis in the rat, mouse, hamster, guinea pig, dog, rabbit, bull, stallion, ram, boar, quail, monkey, and man. The program is flexible and permits the user to alter the cycle duration time and the frequency of each stage. Compiled for use on personal computers and available on floppy disks free of charge, Stages is menu-driven and requires no knowledge of programming. The program was tested using published data of testicular toxicity and vitamin A synchronization of stages. In general, predicted cell types were similar to those observed; discrepancies between observed and predicted data are discussed. When cycle duration time was changed, predicted data for stage synchronization coincided with the observed data. This program will improve the speed and accuracy of studying factors that affect spermatogenesis. By using Stages, it is possible to predict the target cell types in a toxicity study and to track affected cells over long periods of time. Predicted cell types may also indicate which cells to examine biochemically as well as morphologically in subsequent experiments. The program will also be useful to beginning students learning the complex patterns of cellular associations and the progression of germ cells in the cycle of the seminiferous epithelium. PMID- 1601740 TI - The effect of ketoconazole on endocrine and reproductive parameters in male mice and rats. AB - Ketoconazole has been shown to reduce steroidogenesis by inhibiting the cytochrome P-450 enzymes in these pathways. This finding, along with the observation that the compound reduces sperm motility, led us to study the effectiveness of ketoconazole as a male contraceptive agent administered in acute and chronic studies of both rats and mice. Four hours after a single administration, male rats showed significant reductions in both serum testosterone and corticosterone levels that completely recovered (testosterone) or nearly recovered (corticosterone) 24 hours after administration. Chronic administration of ketoconazole to male rats and mice resulted in steroid levels comparable with those of control animals. Epididymal sperm motility was only slightly reduced in male mice 4 hours after administration of the drug. No effect on sperm motility was noted after chronic administration in either species studied. In vitro exposure of epididymal sperm to ketoconazole resulted in a significant reduction of sperm motility. Breeding trials after ketoconazole administration resulted in normal fertility and fecundity even at the highest dosage studied. The lack of correlation between steroid levels and sperm immobilization, along with rapid in vivo and in vitro effects on sperm motility, suggests that the reduction in sperm motility is not related to a decrease in steroid levels. From these data, the authors conclude that ketoconazole is probably not a viable approach to the development of a male contraceptive. PMID- 1601741 TI - An investigation of the requirement for increased LH secretion during the compensatory response in androgen secretion after unilateral castration of the adult rat. AB - The endocrine mechanisms underlying the response to unilateral castration were examined by determining systemic androgen and luteinizing hormone (LH) concentrations, as well as testicular vein androgen at 3, 6, 12, and 24 hours after sham surgery and castration. Systemic androgen was significantly depressed 3 hours after unilateral castration, but had recovered to concentrations observed in sham operated rats at 6, 12, and 24 hours. The recovery of serum androgen after castration was apparently due to increased testicular secretion of androgen, seen as a significant increase in testicular vein androgen. Systemic concentrations of bioactive and immunoactive LH were significantly increased only at 6 hours after castration. The authors next examined whether the increase in LH was necessary for the compensatory secretion of androgen seen after castration. This was accomplished by examining the response to castration when circulating LH was prevented from changing by suppressing endogenous LH secretion with subcutaneous steroid implants and maintaining circulating LH with subcutaneous osmotic pumps containing ovine LH. The compensatory increase in testicular vein androgen was observed 1 and 7 days after castration in rats bearing sham implants. When circulating LH was prevented from changing by using the combination of steroids and LH, however, compensatory secretion of androgen did not occur 1 and 7 days after castration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601742 TI - Evidence for increased lipid peroxidative damage and loss of superoxide dismutase activity as a mode of sublethal cryodamage to human sperm during cryopreservation. AB - Cryopreservation of human sperm, now generally required in donor insemination programs, adversely affects the sperm in terms of standard sperm evaluation parameters and fertilizing ability. The freeze-thaw process appears to produce sublethal damage that appears only after a delay. The authors hypothesized that cryopreservation enhanced peroxidation of sperm membrane lipids, based on previous studies of sperm lipid peroxidation, which showed that the effects of peroxidative damage became evident only after a delay, depending on the peroxidation rate. The effect of cryopreservation on the phospholipid content, the composition of the acyl moieties of the phospholipids, and the activities of the peroxidation protective enzymes, superoxide dismutase (SOD) and glutathione peroxidase plus reductase, in human sperm were examined to test the hypothesis. Parallel determinations were made of the percent motility, the average path velocity of the motile cells, and the time to loss of motility under specified aerobic incubation conditions, which gives a good estimate of the lipid peroxidation rate. The phospholipid content decreases after cryopreservation, with loss of phosphatidylcholine and phosphatidylethanolamine being the more pronounced. Polyunsaturated acyl moieties were also preferentially lost. This loss pattern is observed also from lipid peroxidation. The activities of glutathione peroxidase plus reductase remained unchanged. The sperm SOD activities varied widely between samples before cryopreservation. In all samples there was a decline in SOD activity after freeze-thaw, but the extent of the decline was also widely variable. The time to loss of motility declined in parallel with SOD activity, and a strong correlation (R2 greater than 0.9) between SOD activity and time to loss of motility was found for all samples, before and after freeze-thaw. The authors conclude that cryopreservation does enhance lipid peroxidation in human sperm, as hypothesized, and that this enhancement is mediated at least in part by the loss of SOD activity occurring during the process. PMID- 1601744 TI - The lack of effect of tumor necrosis factor-alpha, interleukin-1-alpha, and interferon-gamma on human sperm motility in vitro. AB - Whether cytokines present in human peritoneal fluid reduce sperm motility, and thus contribute to infertility, is investigated. The human recombinant cytokines, tumor necrosis factor-alpha, interleukin-1-alpha, and interferon-gamma, were incubated with motile human sperm obtained from fertile men and separated by the swim-up technique. These cytokines, alone or in combination, in higher doses than those observed in vivo (greater than or equal to 25,000 U/ml), did not alter the percentage of motile sperm after 90 minutes, 24 hours, and 48 hours under standard culture conditions. Similarly, penetration of a column of bovine cervical mucus was unchanged after preincubation of the sperm with individual cytokines or combinations of several cytokines for 24 hours. In contrast to those given in previous reports, these dta do not support a direct effect of tumor necrosis factor-alpha, interleukin-1-alpha, or interferon-gamma on sperm motility, and suggest that other soluble factors are responsible for the observed effects of peritoneal fluid on sperm motility in vitro. PMID- 1601743 TI - Binding of methyltrienolone to androgen receptors in human skin fibroblasts is enhanced by insulin. AB - Previous reports have suggested a relationship between hyperinsulinemia and increased androgen secretion leading to female virilization, but no report has been made of the effects of insulin on androgen receptors. The authors tested the in vitro effect of insulin on the binding of methyltrienolone (R1881) to androgen receptors of cultured genital skin fibroblasts preincubated with serum-free medium in the absence and presence of insulin (100 ng/mL, ie, 2600 microU/mL) for 18 hours at 37 degrees C. Insulin increased specific binding of R1881 by 35% (range, 13% to 75%). Scatchard analysis of androgen receptor binding demonstrated a similar increase in the number of binding sites, whereas binding affinity remained unchanged. The increase in androgen receptors was dose dependent (maximum effect at 25 ng insulin/mL) and time dependent (maximum effect occurring after 12 hours). DNA measurements indicated that insulin increased binding sites per cell rather than altering the cell number. Insulin increased total protein concentration to an extent similar to that observed for the increase in androgen receptor binding sites. Cycloheximide, but no actinomycin D, inhibited the effect of insulin on androgen receptor binding. The authors' data suggest that insulin induces an increase in the number of androgen receptors per cell as part of a general anabolic effect on cellular protein content. PMID- 1601745 TI - Human interleukin-1 alpha crosses the blood-testis barriers of the mouse. AB - Interleukin-1 alpha (IL-1 alpha) has been shown to have direct effects on the gonads, affecting steroidal secretion, DNA synthesis by spermatogonia, and the immune function of the testes. It is unclear, however, how IL-1 alpha exerts these effects because the testis is partitioned into basal and adluminal compartments by both a vascular and a Sertoli cell barrier. The authors used a highly sensitive method to quantify the unidirectional flux rates (Ki) into the testis of technetium pertechnetate-labeled human albumin (T-alb), a compound that does not readily cross the vascular barrier, and human IL-1 alpha radioactively labeled with 125I (I-IL). The entry rate (Ki) was almost six times greater for I IL than for T-alb. Part of the enhanced entry of I-IL was due to a saturable transport system. Nearly 0.2% of the total injection had entered the testes 60 minutes after intravenous administration, and more than 75% of that amount was not accounted for by the albumin space. Collection of testicular interstitial fluid from the basal compartment and seminiferous tubule fluid from the adluminal compartment showed preferential entry of I-IL into these compartments. Analysis by high-pressure liquid chromatography or radioactivity recovered from the testis showed that intact I-IL was entering the testis. The leakiness of the blood testis barrier was measured by the rate of entry for T-alb, which was not altered by injection of unlabeled human IL-1 alpha in doses of up to 50 micrograms/kg (5 x 10(6) U/kg), and by the wet weight of the testes. The results show that circulating IL-1 alpha can have direct access to the testis, supporting previous studies suggesting a direct effect of IL-1 alpha on gonadal function. PMID- 1601746 TI - Effect of dilauroylphosphatidylcholine on human spermatozoa. AB - To achieve higher rates of acrosomal loss for in vitro studies of human sperm function, the effect of liposomes prepared from the phospholipid, dilauroylphosphatidylcholine (PC12), on human spermatozoa was investigated. In general, acrosome loss was induced with PC12 with an associated decline in the percentage of motile spermatozoa. Reduction of bovine serum albumin concentration in the incubation medium from 12 mg/mL to 3 mg/mL resulted in a more pronounced effect of PC12, with a significant reduction (P less than 0.001) in the percentage of motile spermatozoa within 1 hour of incubation with PC12. The percentage of spermatozoa observed to be acrosome-free under staining with fluorescein-conjugated Concanavalin A lectin was significantly reduced (P less than 0.05) when spermatozoa were incubated with PC12 (260 mumol/L) in the absence of calcium. The percentage of motile spermatozoa was not different during PC12 incubations when Ca2+ concentration (0, 2.5, and 5 mmol/L) was altered. An active motility pattern was restored in PC12-treated human spermatozoa by subsequent incubation in a defined medium containing 7.5 mmol/L adenosine 5'-triphosphate and 20 mumol/L cyclic adenosine 3', 5'-monophosphate. It was demonstrated that PC12-treated human spermatozoa were capable of binding to the zona pellucida of salt-stored human oocytes once an active motility pattern had been restored. PMID- 1601747 TI - Testicular regulation of epididymal protein secretion. AB - The effects of different androgen and testicular fluid levels on the protein synthesis and secretion of the epididymis of mice and rats were examined. In mice, the in vitro protein synthesis and secretion of five epididymal segments were measured from 3 days up to 8 weeks after efferent duct ligation. During the entire period, alterations in the rate of protein secretion per milligram tissue were small. At 8 weeks, the mean rate of protein synthesis per milligram ligated epididymal tissue was 80% of that of the control side. As a consequence of the weight loss of the ligated epididymis, however, the protein secretion per organ can be estimated to be reduced by 50%. Changes in the protein profile were only found in the proximal segment, where a 40-kd protein appeared and a 29-kd protein disappeared. In rats, the effects of efferent duct ligation were studied in vivo for up to 8 months. Structural changes were present both in the proximal and in the distal epididymis. The most conspicuous change in the protein profile of secretory proteins was the disappearance of a 27-kd protein from the proximal segment. In the distal epididymis, a 32-kd protein was no longer secreted. In mice, the effects of castration on the profile of secreted proteins demonstrated that, without androgen stimulation, some proteins are still secreted 6 weeks after castration. Administering low or high doses of testosterone propionate to castrated mice resulted in almost similar profiles of secretory proteins. However one protein secreted in the proximal epididymis was preferentially stimulated by the high dose of testosterone propionate. PMID- 1601748 TI - Heterogeneity of adult mouse Leydig cells with different buoyant densities. AB - The authors investigated the morphologic characteristics and human chorionic gonadotrophin (hCG)-stimulated testosterone production of adult mouse Leydig cells in vitro, which have different buoyant densities. Leydig cells from five testes of Swiss outbred male mice (15 weeks old) were isolated and purified by mechanical dispersion followed by density gradient centrifugation using Percoll. Two groups of Leydig cells were obtained with different buoyant densities: group 1 had densities of 1.0667 to 1.0515 g/cm3 and group 2 had densities of 1.0514 to 1.0366 g/cm3. In vitro testosterone production of these Leydig cells, in response to different doses of hCG (0, 5, 25, 125, 625, and 3125 pg/mL), was determined by radioimmunoassay. Leydig cells were fixed and processed for electron microscopic stereology to quantify the organelles by volumes and surface area. In Leydig cells of Group 1, testosterone production per cell in vitro in response to 0 and 5 pg/mL hCG was not significantly different (P greater than 0.05). Increases in the dose up to 25 pg/mL produced a significant increase (P less than 0.05) in testosterone production, although hCG doses of 125 and 625 pg/mL did not produce further increases in testosterone levels. However, 3125 pg/mL hCG further elevated the testosterone production by those Leydig cells with high buoyant density. In Leydig cells in group 2, the patterns of testosterone production in response to hCG doses of 0, 5, and 25 pg/mL were similar to those of Leydig cells in group 1. Those Leydig cells with low buoyant density, however, were unable to stimulate further testosterone production by an hCG dose of 3125 pg/mL.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601749 TI - Cryopreservation of human semen. Comparison of cryopreservatives, sources of variability, and prediction of post-thaw survival. AB - Human semen was cryopreserved using Human Sperm Preservation Medium, TEST-Yolk buffer, or glycerol alone. Sperm characteristics for each specimen were measured before and after freezing to determine which cryopreservative resulted in better cryosurvival and recovery of motile sperm. Sperm frozen in Human Sperm Preservation Medium had a significantly better recovery of all semen parameters (motility, velocity, and recovery) than either TEST-Yolk or glycerol alone. Statistical analyses also were done to examine the variability between and within donor semen specimens. Differences between donors, between specimens, and measurements within donors all contributed to variability of sperm characteristics. Specimen-to-specimen variability for a given donor represented 12% to 47% of the total variability, whereas processing and measurement variability represented 12% to 41%. Donors also varied in the ability of their sperm to tolerate freezing. There was a relationship between motile count after dilution with cryopreservative and post-thaw motile count. This relationship allows the prediction of poor-thaw survival before freezing a specimen. PMID- 1601750 TI - The taurine and hypotaurine content of human semen. AB - Taurine and hypotaurine levels were measured in human sperm and seminal fluid. Sperm taurine ranged from 17 nmol/mg DNA to 348 nmol/mg DNA, and hypotaurine from 0 nmol/mg DNA to 251 nmol/mg DNA. Seminal fluid contained 319 mumol/L to 1590 mumol/L of taurine, but no detectable hypotaurine. The coefficient of variation in multiple ejaculates from a single man for these components ranged from 12% for hypotaurine to 24% for seminal fluid taurine, indicating a relative constancy in their concentrations. Sperm hypotaurine content was significantly correlated with sperm morphology, sperm relative forward progression, the percentage of motile sperm, and the total number of sperm in the ejaculate. By contrast, sperm taurine content was negatively correlated with these parameters. The mean hypotaurine content of sperm from 8 fertile men was 149 +/- 92 nmol/mg DNA, four times higher than that of sperm from 9 infertile men, which was 35 +/- 19 nmol/mg DNA (P = 0.011). In contrast, the mean sperm taurine content of the fertile men was lower than that of the infertile men (83 +/- 33 nmol/mg DNA versus 168 +/- 119 nmol/mg DNA, respectively; P = 0.07). Seminal fluid taurine concentrations, however, were similar for both groups. Hypotaurine, an antioxidant, may play an important role in protecting sperm from reactive oxygen species. Higher concentrations of taurine in the sperm of infertile men suggest that accelerated oxidation of hypotaurine to taurine may accompany the observed decline in other sperm parameters. PMID- 1601751 TI - Factors involved in the enhanced efficacy against gram-negative bacteria of fourth generation cephalosporins. AB - The fourth generation cephalosporins, cefpirome and cefepime, demonstrate better activity against strains of Enterobacter cloacae with derepressed beta-lactamase than the third generation compounds cefotaxime and ceftriaxone. Several methodological refinements were used to measure the parameters, predicted by the Zimmermann-Rosselet equation to be important in the efficacy of beta-lactams. Outer membrane permeability was measured by a novel HPLC method. The kinetics of interaction of purified beta-lactamase with beta-lactams were estimated to calculate the inhibition and catalytic constants. The periplasmic concentration of beta-lactams leading to growth inhibition of cells was determined by substituting the above parameters into the Zimmermann-Rosselet equation. Consideration of these three factors allowed accurate prediction of MICs in isogenic E. cloacae strains with differing porin or beta-lactamase contents. The fourth generation cephalosporins had markedly reduced affinity for beta-lactamase and increased outer membrane permeability when compared to the third generation cephalosporins. Such advantages were only partly offset by a lower stability of complexes with beta-lactamase and reduced affinity for their targets. PMID- 1601752 TI - Predominant pathogens in hospital infections. AB - To determine the distribution of pathogens causing nosocomial infections in United States hospitals, we analysed data from the National Nosocomial Infections Surveillance (NNIS) System. From October 1986 to December 1990, amongst hospitals conducting hospital-wide surveillance, the five most commonly reported pathogens were Escherichia coli (13.7%), Staphylococcus aureus (11.2%), enterococci (10.7%), Pseudomonas aeruginosa (10.1%), and coagulase-negative staphylococci (9.7%). The commonest pathogens reported by site included, bloodstream: coagulase negative staphylococci, S. aureus, enterococci, E. coli, and Candida spp.; lower respiratory tract infection: S. aureus, P. aeruginosa and Enterobacter spp.; surgical wound infection: S. aureus, enterococci and coagulase-negative staphylococci; and urinary tract infection: E. coli, enterococci, and P. aeruginosa. Among hospitals conducting intensive care unit (ICU) surveillance, the commonest pathogens were P. aeruginosa (12.4%), S. aureus (12.3%), coagulase negative staphylococci (10.2%), Candida spp. (10.1%), Enterobacter spp. and enterococci (8.6% each). In the ICUs, the commonest pathogens found in the bloodstream were coagulase-negative staphylococci, S. aureus, and enterococci; in lower respiratory tract infections P. aeruginosa, S. aureus, and enterococci; in surgical wound infections enterococci, coagulase-negative staphylococci, and Enterobacter spp. and in urinary tract infections Candida spp., E. coli, enterococci, P. aeruginosa, and Enterobacter spp. These data show that S. aureus, E. coli and P. aeruginosa remain important nosocomial pathogens, that coagulase negative staphylococci, enterococci and C. albicans are pathogens of increasing importance, and that the distribution of pathogens differs by site and hospital location. PMID- 1601753 TI - The in-vitro antibacterial activity of a combination of cefpirome or cefoperazone with vancomycin against enterococci and Staphylococcus aureus. AB - Cefpirome, cefoperazone and ceftazidime were tested for their in-vitro activity against Enterococcus faecalis and methicillin-resistant Staphylococcus aureus (MRSA) isolates. Cefpirome was the most active cephalosporin followed by cefoperazone. Ceftazidime had only very limited activity against these strains. In experiments with cefpirome/vancomycin and cefoperazone/vancomycin combinations, synergy was detected against most MRSA strains and some enterococci. Antagonism did not occur. PMID- 1601754 TI - Pharmacokinetics of cefpirome administered intravenously or intramuscularly to rats and dogs. AB - The pharmacokinetic profile of cefpirome was evaluated in rats and dogs after a single intravenous or intramuscular dose. A two-compartment open model was used for the calculation of the pharmacokinetic parameters for both routes of administration. The elimination half-lives after intravenous and intramuscular administration of 20 mg/kg cefpirome did not differ significantly and ranged from 0.4 h in rats to 1.1 h in dogs. Cefpirome was mainly excreted via the kidneys. After iv or im dosing of the compound, between 80% (dogs) and 90% (rats) was recovered in urine within 24 h. The bioavailability of cefpirome in rats and dogs after both routes of administration was almost identical when calculated either by the AUC or the urinary recovery rates. PMID- 1601755 TI - Animal models as predictors of outcome of therapy with broad spectrum cephalosporins. AB - Broad spectrum cephalosporins have been studied extensively in animal models of experimental infections. There is generally good correlation between the results of therapy of experimental infections and clinical trials in humans. However, the results of animal model studies are better predictors of the failure than of the success of a chemotherapeutic regimen. Cefotaxime and the new 'fourth' generation agent, cefpirome, were comparable in the treatment of experimental meningitis caused by Streptococcus pneumoniae. Cefpirome was the most effective cephalosporin as therapy for methicillin-susceptible Staphylococcus aureus experimental endocarditis. The most effective broad spectrum cephalosporins for the treatment of Gram-negative experimental pneumonia were cefpirome, cefotaxime and cefodizime. Cefpirome was equivalent to ceftazidime or cefazolin as treatment for Pseudomonas aeruginosa or methicillin-susceptible S. aureus experimental osteomyelitis. Because of its potent activity in vitro and in animal models of experimental infections caused by methicillin-susceptible S. aureus and Gram negative bacilli, cefpirome may offer a therapeutic advantage over currently available broad spectrum cephalosporins. PMID- 1601756 TI - Lack of interaction between cefpirome and alcohol. AB - An observer-blind randomized, placebo-controlled, crossover study was conducted in 22 healthy male subjects. They received 2 g cefpirome or placebo intravenously following an overnight fast. One hour later they consumed a single 0.5 g/kg dose of alcohol. The treatments were reversed after a seven-day 'washout' period. Subjects were evaluated for any adverse events or 'disulfiram-like' symptoms. The effects of cefpirome on the pharmacokinetics of alcohol were also studied. There were no statistically significant differences in mean values for the various pharmacokinetic parameters for plasma alcohol between the cefpirome and placebo treatment groups. There were no side effects or 'disulfiram-like' reactions following consumption of alcohol in either group. A single iv dose of 2 g cefpirome was well-tolerated in healthy males and, moreover, pre-treatment with cefpirome did not adversely affect the metabolism of alcohol in these subjects. PMID- 1601757 TI - Cerebrospinal fluid penetration of cefpirome in patients with non-inflamed meninges. AB - Twenty patients (mean age 52 +/- 12 years, mean weight 75 +/- 15 kg) scheduled for elective myelogram or spinal anaesthesia were enrolled to determine the cerebrospinal fluid (CSF) penetration of a new expanded spectrum cephalosporin antibiotic, cefpirome (HR-810). A single 2 g intravenous dose of cefpirome was administered as a bolus between 1 and 8 h before lumbar puncture. Blood samples were collected at 15 pre-determined times and a single CSF sample was obtained at the time of lumbar puncture. Serum and CSF cefpirome concentrations were determined by high performance liquid chromatography. The mean maximal serum concentration of cefpirome was 264 +/- 76 mg/L. A mean steady-state volume of distribution of 20 +/- 4 L, clearance of 7.4 +/- 1.3 L/h, and half-life of 2.5 +/ 0.5 h were determined. Mean CSF concentrations were 0.50 +/- 0.11 mg/L at 1-2 h post dose (n = 4), 0.57 +/- 0.13 mg/L at 2-4 h post dose (n = 4), 0.76 +/- 0.34 mg/L at 4-6 h post dose (n = 7), and 0.83 +/- 0.29 mg/L at 6-8.3 h post dose (n = 5). Blood:brain barrier permeability to cefpirome may not be a limiting factor as CSF concentrations were rapidly attained. Further studies are required to determine the mechanism of cefpirome transport between plasma and CSF. PMID- 1601758 TI - Diffusion of cefpirome into the cerebrospinal fluid of patients with purulent meningitis. AB - We evaluated the diffusion of cefpirome into the cerebrospinal fluid (CSF) of 25 patients with bacterial meningitis or ventriculitis who were receiving conventional antibiotic treatment. A single cefpirome dose of 2 g was infused at day 2-3 after the onset of therapy. Concentrations of cefpirome in serum and CSF obtained at 2, 4, 8 or 12 h after the infusion were determined by high performance liquid chromatography. The mean (+/- S.E.M.) concentrations of cefpirome in CSF ranged from 2.26 +/- 1.16 to 4.17 +/- 0.83 mg/L. These concentrations were higher than the MBCs for the pathogens usually responsible for bacterial meningitis. PMID- 1601759 TI - Safety, tolerance and pharmacokinetics of cefpirome administered intramuscularly to healthy subjects. AB - The pharmacokinetics of cefpirome were studied in healthy male subjects following single (0.5, 1.0 and 2.0 g) and multiple (1.0 g every 12 h for 3.5 days) intramuscular injections. High pressure liquid chromatography was used to determine cefpirome concentrations in plasma and urine. Cefpirome was absorbed rapidly, mean peak times were 1.6-2.3 h. Pharmacokinetics were linear over the 0.5 to 2.0 g range with mean total body clearance ranging from 148 to 154 mL/min. The peak plasma concentration and area under the curve increased in a dose proportional manner. The terminal half-life (2 h) was not influenced by dose or duration of dosing. There was no drug accumulation after multiple in administrations. About 70-80% of an administered dose was excreted in the urine as unchanged cefpirome. Cefpirome was well tolerated, slight to moderate pain being reported in less than 30% of the injections. PMID- 1601760 TI - In-vitro activity of cefpirome against isolates from patients with urinary tract, lower respiratory tract and wound infections. AB - The in-vitro activity of cefpirome, a new injectable cephalosporin, was compared with that of several other antibiotics against bacterial isolates from hospitalized patients with lower respiratory tract infections, urinary tract infections and wound infections. Minimum inhibitory concentrations were determined for 874 strains against 16 antibiotics using a microtitration technique. Cefpirome showed a very broad spectrum of activity against most pathogens tested. The spectrum included organisms such as Staphylococcus spp., enterococci, Enterobacter spp., and Pseudomonas spp. which are frequently resistant to third generation cephalosporins. PMID- 1601761 TI - Toxicity of cefpirome: an overview. AB - Cefpirome is a new cephalosporin antibiotic with a broad antimicrobial spectrum in vitro. This includes strains which are frequently resistant to other cephalosporins (Seibert et al., 1983). This report gives a summary of the toxicological investigations on cefpirome. PMID- 1601762 TI - Comparison of clinical response to cefpirome treatment and minimum inhibitory concentration of causative isolates. Microbiological and Clinical Study Groups. AB - Three hundred and forty-five clinical isolates from patients treated with cefpirome were studied using an MIC methodology to develop tentative breakpoints for cefpirome, and to correlate clinical success with in-vitro susceptibility. No relationship between elimination, persistence and MIC of potential pathogens was found. There was, however, a close relationship between clinical cure and improvement and eradication of causative organisms. Based on the data, tentative breakpoints of less than 4 mg/L for sensitive and greater than 16 mg/L for resistance, at a cefpirome dose of 2.0 g bid or 1.0 g bid for urinary tract infection, are suggested. PMID- 1601763 TI - Influence of cefpirome on pharyngeal and faecal flora after single and multiple intravenous administrations of cefpirome to healthy volunteers. AB - The effect of single and multiple 2 g doses of i.v. cefpirome on pharyngeal and faecal flora was studied in ten male volunteers. There was no effect on pharyngeal flora. After a single dose, cefpirome had no effect on faecal flora but numbers of Escherichia coli were reduced below the detection limit during multiple dose treatment. No strains of Clostridium difficile were selected in this study and only a slight increase in the numbers of Candida spp. were found. Cefpirome, therefore, has little, if any, effect on faecal or pharyngeal flora. PMID- 1601764 TI - Prospective randomized phase II study of intravenous cefpirome 1g or 2g bd in the treatment of hospitalized patients with different infections. Cefpirome Study Group. AB - Two hundred and seventy-six hospitalized patients with severe infection (complicated UTI, pneumonia, skin and soft tissue infection or septicaemia) were randomly allocated to receive either 1g or 2g cefpirome bd. Two hundred and seventy-four patients were evaluable for tolerance, 210 for bacteriological efficacy. The two groups were similar in terms of underlying disease, age, sex, and general condition on admission. The overall clinical and bacteriological response rates were 97/103 (94%) and 68/76 (90%) respectively in the 1g group, compared with 102/107 (95%) and 67/71 (94%) in the 2g group. There was no significant difference between the treatment groups. Eighteen adverse events, possibly or probably drug related, were reported (7 in the 1g group, 11 in the 2g group). This resulted in discontinuation of therapy in four cases (two in each group). Fourteen of the adverse events were local (five receiving 1g, nine receiving 2g), mainly phlebitis or pain at the injection site. Thirteen patients died during the study period (up to 14 days after the last dose) but in no case was death attributed to cefpirome. A review of routine laboratory parameters revealed no abnormalities which could definitely be attributed to cefpirome although in four cases a relationship was considered possible; these included two increases in serum creatinine, one increase in SGPT, and one episode of neutropenia. Cefpirome administered as 1 or 2g twice daily was a well tolerated, effective agent for the treatment of severe sepsis in hospitalized patients. PMID- 1601765 TI - Cefpirome versus ceftazidime in the treatment of urinary tract infections. AB - In an open, randomized multiclinic trial, hospitalized patients with upper or complicated lower urinary tract infections requiring treatment with a parenteral antibiotic were randomized to receive 1 g doses of cefpirome (594 patients) or ceftazidime (303 patients) 12 hourly for at least five days. Cefpirome was considerably more active in vitro than ceftazidime against Gram-positive pathogens isolated from the urine samples. At the early follow-up, 2-15 days after treatment, clinical cure was achieved in 86% and 82% of the patients in the cefpirome and ceftazidime groups respectively. Elimination of the causative pathogen without recurrence or early reinfection was achieved in 87% of the patients in both groups. Drug related adverse events occurred in 8.9% of cefpirome treated patients and in 4.6% of those receiving ceftazidime. No specific type of adverse reaction accounted for this difference. Treatment was discontinued because of adverse events in 2.5% and 1.7% of the patients respectively. Cefpirome was found to be safe and at least as effective as ceftazidime for the treatment of urinary tract infections in hospitalized patients. PMID- 1601766 TI - Life in space. PMID- 1601767 TI - Neurobiology of muscle fatigue. AB - Muscle fatigue encompasses a class of acute effects that impair motor performance. The mechanisms that can produce fatigue involve all elements of the motor system, from a failure of the formulation of the descending drive provided by suprasegmental centers to a reduction in the activity of the contractile proteins. We propose four themes that provide a basis for the systematic evaluation of the neural and neuromuscular fatigue mechanisms: 1) task dependency to identify the conditions that activate the various mechanisms; 2) force fatigability relationship to explore the interaction between the mechanisms that results in a hyperbolic relationship between force and endurance time; 3) muscle wisdom to examine the association among a concurrent decline in force, relaxation rate, and motor neuron discharge that results in an optimization of force; and 4) sense of effort to determine the role of effort in the impairment of performance. On the basis of this perspective with an emphasis on neural mechanisms, we suggest a number of experiments to advance our understanding of the neurobiology of muscle fatigue. PMID- 1601768 TI - Effects of training on lactate production and removal during progressive exercise in humans. AB - To determine whether the reduced blood lactate concentrations [La] during submaximal exercise in humans after endurance training result from a decreased rate of lactate appearance (Ra) or an increased rate of lactate metabolic clearance (MCR), interrelationships among blood [La], lactate Ra, and lactate MCR were investigated in eight untrained men during progressive exercise before and after a 9-wk endurance training program. Radioisotope dilution measurements of L [U-14C]lactate revealed that the slower rise in blood [La] with increasing O2 uptake (VO2) after training was due to a reduced lactate Ra at the lower work rates [VO2 less than 2.27 l/min, less than 60% maximum VO2 (VO2max); P less than 0.01]. At power outputs closer to maximum, peak lactate Ra values before (215 +/- 28 mumol.min-1.kg-1) and after training (244 +/- 12 mumol.min-1.kg-1) became similar. In contrast, submaximal (less than 75% VO2max) and peak lactate MCR values were higher after than before training (40 +/- 3 vs. 31 +/- 4 ml.min-1.kg 1, P less than 0.05). Thus the lower blood [La] values during exercise after training in this study were caused by a diminished lactate Ra at low absolute and relative work rates and an elevated MCR at higher absolute and all relative work rates during exercise. PMID- 1601769 TI - VA/Q distribution during heavy exercise and recovery in humans: implications for pulmonary edema. AB - Ventilation-perfusion (VA/Q) inequality has been shown to increase with exercise. Potential mechanisms for this increase include nonuniform pulmonary vasoconstriction, ventilatory time constant inequality, reduced large airway gas mixing, and development of interstitial pulmonary edema. We hypothesized that persistence of VA/Q mismatch after ventilation and cardiac output subside during recovery would be consistent with edema; however, rapid resolution would suggest mechanisms related to changes in ventilation and blood flow per se. Thirteen healthy males performed near-maximal cycle ergometry at an inspiratory PO2 of 91 Torr (because hypoxia accentuates VA/Q mismatch on exercise). Cardiorespiratory variables and inert gas elimination patterns were measured at rest, during exercise, and between 2 and 30 min of recovery. Two profiles of VA/Q distribution behavior emerged during heavy exercise: in group 1 an increase in VA/Q mismatch (log SDQ of 0.35 +/- 0.02 at rest and 0.44 +/- 0.02 at exercise; P less than 0.05, n = 7) and in group 2 no change in VA/Q mismatch (n = 6). There were no differences in anthropometric data, work rate, O2 uptake, or ventilation during heavy exercise between groups. Group 1 demonstrated significantly greater VA/Q inequality, lower vital capacity, and higher forced expiratory flow at 25-75% of forced vital capacity for the first 20 min during recovery than group 2. Cardiac index was higher in group 1 both during heavy exercise and 4 and 6 min postexercise. However, both ventilation and cardiac output returned toward baseline values more rapidly than did VA/Q relationships. Arterial pH was lower in group 1 during exercise and recovery. We conclude that greater VA/Q inequality in group 1 and its persistence during recovery are consistent with the hypothesis that edema occurs and contributes to the increase in VA/Q inequality during exercise. This is supported by observation of greater blood flows and acidosis and, presumably therefore, higher pulmonary vascular pressures in such subjects. PMID- 1601770 TI - Calf blood flow and posture: Doppler ultrasound calibrated by plethysmography. AB - A procedure was developed that enables measurement of rapid variations in calf blood flow during voluntary rhythmic contraction of the calf muscles in supine, sitting, and standing positions. During the exercise, maximum blood velocity is measured by Doppler ultrasound equipment in the popliteal artery. The Doppler signals are calibrated by plethysmography to enable calculation of blood flow during exercise in ml.100 ml-1.min-1. Knowledge of the cross-sectional area of the vessel and the angle of insonation is not required in this procedure. Evaluation of the calibration method with 10 healthy volunteers showed that for each subject a new calibration was necessary after a change in posture; the relationship between the blood flow and the maximum Doppler frequency averaged over one heart cycle was linear for each calibration. PMID- 1601771 TI - Calf blood flow and posture: Doppler ultrasound measurements during and after exercise. AB - To investigate the joint effects of body posture and calf muscle pump, the calf blood flow of eight healthy volunteers was measured with pulsed Doppler equipment during and after 3 min of rhythmic exercise on a calf ergometer in the supine, sitting, and standing postures. Muscle contractions seriously impeded calf blood flow. Consequently, blood flow occurred mainly between contractions and reached a plateau that lasted at least the final 100 s of each exercise series. After exercise the blood flow decreased much faster in the sitting and standing postures than in the supine posture. There was no difference in blood flow between various postures during the same submaximal exercise. However, subjects in the standing posture were able to perform exercise with a higher load than in the supine posture, and blood flow in the standing posture could become twice as high as in the supine posture. We conclude that calf blood flow is regulated according to needs; available perfusion pressure determined maximal blood flow and exercise; and compared with the supine posture, the standing posture and calf muscle pump increase the perfusion pressure. PMID- 1601772 TI - Microvascular and macrovascular endothelial cells produce different constrictor substances. AB - The media from cultured microvascular and macrovascular endothelial cells (conditioned media, CM) were collected and tested for constrictor activity in sheep coronary artery rings and tracheal smooth muscle strips in vitro (isometric force), expressed as percentage of contraction produced by 80 mM KCl. Both microvascular (micro) and macrovascular (macro) CM caused a sustained slow-onset contraction (P less than 0.05) of the coronary artery rings by 71 +/- 10% (micro; n = 7) and 67 +/- 8% (macro; n = 6) and tracheal smooth muscle strips by 33 +/- 14% (micro; n = 6) and 34 +/- 6% (macro; n = 11); the calcium antagonist gallopamil (10(-7) M) attenuated these effects by 25-55%. Unconditioned medium and medium conditioned by cultured tracheal smooth muscle cells had no constrictor activity on coronary artery rings or tracheal smooth muscle strips. Synthetic endothelin (ET-1) also produced contraction of coronary artery rings and tracheal smooth muscle strips. The mean levels of ET-1 measured by radioimmunoassay were 1,200 pg/ml in the macro CM and 33 pg/ml in the micro CM. Depleting macro CM of ET-1 by affinity columns constructed with protein A agarose and anti-ET-1 antibody removed the contractile activity for coronary artery rings and tracheal smooth muscle strips. Thus ET-1 did not appear to be the contractile substance in the micro CM. Preliminary characterization of the contractile substance in micro CM revealed that it was heat stable, had a molecular weight of less than 10,000, was inactivated by trypsin, and retained its activity after two cycles of freeze-thawing.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601773 TI - Differential metabolic responses of periarticular ligaments and tendon to joint immobilization. AB - Parameters of collagen metabolic behavior were analyzed in the periarticular connective tissues, i.e., medial collateral ligament (MCL), anterior cruciate ligament (ACL), and patellar tendon (PT), of control and immobilized rabbit knees. Two periods of immobilization were studied: 9 and 12 wk. Collagen turnover and collagen cross-links were quantitatively assessed in the three tissues. The results showed that after 9 wk both synthesis and degradation were significantly increased in the MCL and ACL, whereas the PT showed lesser effects. After 12 wk all three tissues experienced significant losses of collagen mass, which resulted in tissue atrophy. The concentrations of the reducible collagen cross-links dihydroxylysinonorleucine and hydroxylysinonorleucine in the immobilized MCL and ACL were greater than their respective controls, indicating an increase in collagen synthesis, whereas concentrations of the nonreducible cross-link hydroxypyridinoline were observed to be decreased in these tissues. Of the reducible cross-links in the PT, only hydroxylysinonorleucine was found to be increased over control, whereas hydroxypyridinoline was slightly less concentrated. These results taken together have demonstrated that the ligamentous tissues are more susceptible to the effects of stress deprivation secondary to joint immobilization than the PT, and, in particular, the ACL of the three tissues studied appears to be most vulnerable. PMID- 1601774 TI - Mechanical alteration of blood flow in smoked and unsmoked lung areas after inhalation injury. AB - The degree of pulmonary perfusion may have an important role in the pathogenesis of inhalation injury. We studied this in sheep that had only one lung exposed to smoke. The right lung and upper airway of 12 chronically instrumented sheep were insufflated with cotton smoke. In six animals, the left pulmonary artery was occluded between 4 and 10 h after smoke insufflation. All animals were studied for 24 h and then killed, and lung tissue was harvested. The smoked as well as the air-insufflated lung of all animals showed an increase in wet-to-dry weight ratio and tissue conjugated dienes (products of lipid peroxidation). Neither the intermittent blood flow increase to the smoked lung nor the simultaneous blood flow reduction with a concomitant polymorphonuclear neutrophil entrapment in the air-insufflated lung significantly affected the histopathological outcome of the respective lung. We conclude that tissue damage after inhalation injury cannot be diminished by increasing the flow to smoked areas. Ischemia-reperfusion injury does not have a major role in the lung damage seen with inhalation injury. PMID- 1601775 TI - Systemic blood flow to the lung after bronchial artery occlusion in anesthetized sheep. AB - To compare the effectiveness of different embolizing agents in reducing or redistributing bronchial arterial blood flow, we measured systemic blood flow to the right lung and trachea in anesthetized sheep by use of the radioactive microsphere method before and 1 h after occlusion of the bronchoesophageal artery (BEA) as follows: injection of 4 ml ethanol (ETOH) into BEA (group 1, n = 5), injection of approximately 0.5 g polyvinyl alcohol particles (PVA) into BEA (group 2, n = 5), or ligation of BEA (group 3, n = 5). After occlusion, angiography showed complete obstruction of the bronchial vessels. There were no changes in tracheal blood flow in any of the groups. Injection of ETOH produced a 75 +/- 14% (SD) reduction in flow to the middle lobe (P less than 0.02) and a 75 +/- 13% reduction to the caudal lobe (P less than 0.01), whereas injection of PVA produced a smaller reduction in flow to these two lobes (41 +/- 66 and 51 +/- 54%, respectively). After BEA ligation there was a 52 +/- 29% reduction in flow to the middle lobe and a 53 +/- 38% reduction to the caudal lobe (P less than 0.05). This study has significant implications both clinically and experimentally; it illustrates the importance of airway collateral circulation, in that apparently complete radiological obstruction of the BEA does not necessarily mean complete obstruction of systemic blood flow. We also conclude that, in experimental studies in which the role of the bronchial circulation in airway pathophysiology is examined, ETOH is the agent of choice. PMID- 1601776 TI - Inhibition of pulmonary surfactant by oleic acid: mechanisms and characteristics. AB - The inhibitory effects of oleic acid (OA) on the surface activity of pulmonary surfactant were characterized by use of the oscillating bubble surfactometer, the Wilhelmy balance, and excised rat lungs. Oscillating bubble studies showed that OA prevented lavaged calf surfactant [0.5 mM phospholipid (PL)] from lowering surface tension below 15 mN/m at or above a molar ratio of OA/PL = 0.5. In contrast to inhibition of surfactant by plasma proteins, increasing the surfactant concentration did not eliminate inhibition by oleic acid, which occurred at OA/PL greater than 0.67 on the oscillating bubble even at surfactant concentrations of 1.5 and 12 mM PL. Studies of surfactant adsorption showed that preformed films of OA had little effect on the adsorption of pulmonary surfactant. Wilhelmy balance studies showed that OA did interfere with the ability of spread films of surfactant to reach low surface tensions during dynamic compression. Further balance experiments with binary films of OA and dipalmitoyl phosphatidylcholine showed that these compounds were miscible in surface films. Together these findings suggested that OA inhibited pulmonary surfactant activity by disrupting the rigid interfacial film responsible for the generation of very low surface tension during dynamic compression. Mechanical studies in excised rat lungs showed that instillation of OA gave altered deflation pressure-volume characteristics with decreased quasi-static compliance, indicating disruption of pulmonary surfactant function in situ. This alteration of mechanics occurred without major changes in the composition of lavaged PLs or in the tissue compliance of the lungs defined by mechanical measurements during inflation-deflation with saline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601777 TI - Ventilatory effects of acetazolamide in cats during hypoxemia. AB - In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg 1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601778 TI - Mechanisms of extracellular reactive oxygen species injury to the pulmonary microvasculature. AB - We investigated the effect of xanthine (X) plus xanthine oxidase (XO) on pulmonary microvascular endothelial permeability in isolated rabbit lungs perfused with Krebs buffer containing bovine serum albumin (5 g/100 ml). Addition of five mU/ml XO and 500 microM X to the perfusate caused a twofold increase in the pulmonary capillary filtration coefficient (Kf,c) 30 min later without increasing the pulmonary capillary pressure. This increase was prevented by allopurinol or catalase but not by superoxide dismutase or dimethyl sulfoxide. Because these data implicated hydrogen peroxide (H2O2) as the injurious agent, we measured its concentration in the perfusate after the addition of X and XO for a 60-min interval. In the absence of lung tissue and albumin, H2O2 increased with time, reaching a concentration of approximately 250 microM by 60 min. If albumin (5 g/100 ml) was added to the perfusate, or in the presence of lung tissue, the corresponding values were 100 microM and less than 10 microM, respectively. To understand the mechanisms of H2O2 scavenging by lung tissue, we added a 250 microM bolus of H2O2 to the lung perfusate. We found that H2O2 was removed rapidly, with a half-life of 0.31 +/- 0.04 (SE) min. This variable was not increased significantly by inhibition of lung catalase activity with sodium azide or inhibition of the lung glutathione redox cycle with 1-chloro-2,4 dinitrobenzene. However, inhibition of both enzymatic systems increased the half life of H2O2 removal to 0.71 +/- 0.09 (SE) min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601779 TI - Endothelin-1-induced pulmonary arterial dilation is reduced by N omega-nitro-L arginine in fetal lambs. AB - Endothelin-1 (ET-1) is a pulmonary vasodilator in the unventilated fetal lamb. The site and mechanism of this vasodilator response were investigated in isolated blood-perfused lungs from nine fetal lambs delivered at 127-140 days gestation. The vascular occlusion technique was used to partition the total pulmonary pressure gradient into pressure gradients across large and small arteries (delta PLA and delta PSA, respectively) and veins (delta PV). Injection of ET-1 (74 ng/kg) into the pulmonary artery significantly decreased delta PLA from 12.4 +/- 2.1 to 5.2 +/- 1.1 mmHg and delta PSA from 49.2 +/- 2.7 to 31.3 +/- 4.9 mmHg. The pressure measured by double occlusion, an estimate of pulmonary capillary pressure, was not altered by ET-1 (15.5 +/- 1.0 vs. 14.8 +/- 1.0 mmHg), indicating that ET-1 had no effect on pulmonary veins. Addition of N omega-nitro L-arginine (estimated perfusate concentration 2-6 mM), an analogue of L-arginine that inhibits the production of endothelium-derived relaxing factor (EDRF), significantly attenuated the dilator responses to acetylcholine (10 micrograms) and ET-1 (74 ng/kg) by 35 and 56%, respectively. These results in unventilated fetal lungs indicate that 1) ET-1 dilates both large and small pulmonary arteries with no effect on pulmonary veins, and 2) this effect is mediated in part through the action of the EDRF pathway. PMID- 1601780 TI - Ca2+ movements in sarcoplasmic reticulum of rat soleus fibers after hindlimb suspension. AB - The functional capacity of skeletal muscle sarcoplasmic reticulum (SR) was examined in the slow soleus of rats submitted to 15 days of disuse produced by hindlimb suspension (HS). By using caffeine-induced contractions of single skinned fibers, Ca2+ uptake, Ca2+ release, and passive Ca2+ leakage through the SR membrane were investigated. In the SR of atrophied muscles, the amounts of Ca2+ uptake and Ca2+ release were significantly higher than in the control muscles and were close to those found for a fast muscle, the plantaris. Moreover, the study of the Ca2+ leakage showed that the time required to empty the SR previously loaded with Ca2+ was reduced by a factor of two after HS. Such disturbances of the Ca2+ movements in the SR suggested that alterations of the SR membrane occurred after HS. The results supported the idea that after hindlimb unweighting the slow soleus muscle acquired SR properties that were very much like those of a faster muscle. PMID- 1601781 TI - Increased energy intake minimizes weight loss in men at high altitude. AB - The hypothesis that high-altitude weight loss can be prevented by increasing energy intake to meet energy requirement was tested in seven men, 23.7 +/- 4.3 (SD) yr, taken to 4,300 m for 21 days. Energy intake required to maintain body weight at sea level was found to be 3,118 +/- 300 kcal/day, as confirmed by nitrogen balance. Basal metabolic rate (BMR), determined by indirect calorimetry, increased 27% on day 2 at altitude and then decreased and reached a plateau at 17% above the sea level BMR by day 10. Energy expended during strenuous activities was 37% lower at altitude than at sea level. Fecal excretion of energy, nitrogen, total fiber, and total volatile fatty acids was not significantly affected by altitude. Energy intake at altitude was adjusted after 1 wk, on the basis of the increased BMR, to 3,452 +/- 452 kcal/day. Mean nitrogen balance at altitude was negative (-0.25 +/- 0.71 g/day) before energy intake was adjusted but rose significantly thereafter (0.20 +/- 0.71 and 0.44 +/- 0.66 g/day during weeks 2 and 3). Mean body weight decreased 2.1 +/- 1.0 kg over the 3 wk of the study, but the rate of weight loss was significantly diminished after the increase in energy intake (201 +/- 75 vs. 72 +/- 48 g/day). Individual regression lines drawn through 7-day segments of body weight showed that in four of seven subjects the slopes of body weight were not significantly different from zero after the 2nd wk. Thus weight loss ceased in four of seven men in whom increased BMR at altitude was compensated with increased energy intake.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601782 TI - Vagal function impairment after exercise training. AB - The present investigation was undertaken to evaluate the vagal function of trained (T) and sedentary (S) rats by use of different approaches in the same animal. After 13 wk of exercise training (treadmill for 1 h 5 times/wk at 26.8 m/min and 15% grade), T rats had a resting heart rate (HR) slightly but significantly lower than S rats (299 +/- 3 vs. 308 +/- 3 beats/min). T rats had marked reduction of the intrinsic HR (329 +/- 4 vs. 369 +/- 5 beats/min) after blockade by methylatropine and propranolol. They also exhibited depressed vagal and sympathetic tonus. Baroreflex bradycardia (phenylephrine injections) was reduced, bradycardic responses produced by electrical stimulation of the vagus were depressed, and responses to methacholine injection were decreased in T rats. Therefore several evidences of vagal function impairment were observed in T rats. The resting bradycardia after exercise training is more likely to be dependent on alterations of the pacemaker cells, inasmuch as the intrinsic HR was markedly reduced. PMID- 1601783 TI - Effects of exercise mode and intensity on postprandial thermogenesis in lean and obese men. AB - To characterize further the impact of exercise before a meal on thermogenesis, the effects of exercise intensity and mode and the duration of the effect of exercise on the thermic effect (TEF) of a 720-kcal mixed meal were compared in 10 lean and 10 obese men (16 +/- 1 vs. 34 +/- 2% fat). In study A, TEF (kcal/3 h) was significantly greater for the lean than the obese men during rest and immediately after 1 h of cycling at 50 and 100 W. TEF was significantly greater after both exercise intensities than during rest for the obese men, but exercise had no effect on TEF in the lean men. In study B, TEF was significantly greater for the lean than the obese men during rest and immediately after 1 h of leg cycling at an O2 consumption of 1.09 l/min but only marginally different after 1 h of arm exercise at the same O2 consumption (P = 0.15). For the obese men, TEF was greater after arm than leg cycling and greater after leg cycling than at rest (P less than 0.01), but TEF was not different among the three conditions for the lean men. In study C, TEF was compared at rest and immediately and 24 h after 1 h of cycling at 100 W. TEF was greater for the lean than the obese men under all conditions (P less than 0.05). For the obese but not the lean men, TEF was greater both immediately after and on the day after exercise than at rest (P less than 0.01). Thus, acute exercise improves but does not normalize the blunted TEF in obesity; a minimally intense bout of exercise is needed to improve TEF; exercise mode alters thermogenesis in the obese men, even at a fixed intensity; and TEF in the obese men is enhanced for as long as 24 h after exercise. PMID- 1601784 TI - Kinetics of CO uptake and diffusing capacity in transition from rest to steady state exercise. AB - In the transition from rest to steady-state exercise, O2 uptake from the lungs (VO2) depends on the product of pulmonary blood flow and pulmonary arteriovenous O2 content difference. The kinetics of pulmonary blood flow are believed to be somewhat faster than changes in pulmonary arteriovenous O2 content difference. We hypothesized that during CO breathing, the kinetics of CO uptake (VCO) and diffusing capacity for CO (DLCO) should be faster than VO2 because changes in pulmonary arteriovenous CO content difference should be relatively small. Six subjects went abruptly from rest to constant exercise (inspired CO fraction = 0.0005) at 40, 60, and 80% of their peak VO2, measured with an incremental test (VO2peak). At all exercise levels, DLCO and VCO rose faster than VO2 (P less than 0.001), and DLCO rose faster than VCO (P less than 0.001). For example, at 40% VO2peak, the time constant (tau) for DLCO in phase 2 was 19 +/- 5 (SD), 24 +/- 5 s for VCO, and 33 +/- 5 s for VO2. Both VCO and DLCO increased with exercise intensity but to a lesser degree than VO2 at all exercise intensities (P less than 0.001). In addition, no significant rise in DLCO was observed between 60 and 80% VO2peak. We conclude that the kinetics of VCO and DLCO are faster than VO2, suggesting that VCO and DLCO kinetics reflect, to a greater extent, changes in pulmonary blood flow and thus recruitment of alveolar-capillary surface area. However, other factors, such as the time course of ventilation, may also be involved.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601785 TI - Effect of deficient muscular glycogenolysis on extramuscular fuel production in exercise. AB - Hormonal, metabolic, and cardiovascular responses to 21 min of cycling in three saline- or glucose-infused men with McArdle's disease were compared with those of matched controls to elucidate whether mobilization of extramuscular fuel is enhanced to compensate for the lack of intramuscular glycogenolysis in patients with McArdle's disease. During exercise, all saline-infused patients compared with controls working at both the same absolute and at similar relative work rates had higher glucose production (31 +/- 7 vs. 19 +/- 5 and 26 +/- 4 mumol.min 1.kg-1) and utilization (34 +/- 8 vs. 22 +/- 2 and 28 +/- 4 mumol.min-1.kg-1); higher plasma glycerol (155 +/- 19 vs. 75 +/- 20 and 90 +/- 22 mumol/l), free fatty acids (487 +/- 175 vs. 295 +/- 47 and 202 +/- 52 mumol/l), growth hormone (7.7 +/- 2.8 vs. 2.6 +/- 1.1 and 3.6 +/- 3.4 mU/l), and cortisol (530 +/- 168 vs. 268 +/- 8 and 367 +/- 80 nmol/l), greater decrease in insulin (delta 57 +/- 4 vs. delta 11 +/- 8 and delta 11 +/- 23 pmol/l), and similar glucose concentrations. Furthermore, norepinephrine, epinephrine, and adrenocorticotropic hormone levels were higher and heart rate and cardiac output were higher during exercise in all patients than in controls at the same absolute work rate. Glucose infusion induced hyperglycemia and hyperinsulinemia in patients and inhibited the exercise induced increases in glucose production, glycerol, free fatty acids, catecholamines, growth hormone, cortisol, and heart rate. In conclusion, feedback from metabolism in contracting muscle enhances hormonal responses and extramuscular substrate mobilization during exercise in McArdle's disease. PMID- 1601786 TI - Skeletal muscle adaptations to endurance training in 60- to 70-yr-old men and women. AB - Previous studies of endurance exercise training in older men and women generally have found only minimal skeletal muscle adaptations to training. To evaluate the possibility that this may have been due to an inadequate training stimulus, we studied 23 healthy older (64 +/- 3 yr) men and women before and after they had trained by walking/jogging at 80% of maximal heart rate for 45 min/day 4 days/wk for 9-12 mo. This training program resulted in a 23% increase in maximal O2 consumption. Needle biopsy samples of the lateral gastrocnemius muscle were obtained before and after training and analyzed for selected histochemical and enzymatic characteristics. The percentage of type I muscle fibers did not change with training. The percentage of type IIb fibers, however, decreased from 19.1 +/ 9.1 to 15.1 +/- 8.1% (P less than 0.001), whereas the percentage of type IIa fibers increased from 22.1 +/- 7.7 to 29.6 +/- 9.1% (P less than 0.05). Training also induced increases in the cross-sectional area of both type I (12%; P less than 0.001) and type IIa fibers (10%; P less than 0.05). Capillary density increased from 257 +/- 43 capillaries/mm2 before training to 310 +/- 48 capillaries/mm2 after training (P less than 0.001) because of increases in the capillary-to-fiber ratio and in the number of capillaries in contact with each fiber. Lactate dehydrogenase activity decreased by 21% (P less than 0.001), whereas the activities of the mitochondrial enzymes succinate dehydrogenase, citrate synthase, and beta-hydroxyacyl-CoA dehydrogenase increased by 24-55% in response to training (P less than 0.001-0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601787 TI - Effects of acid-base status on acute hypoxic pulmonary vasoconstriction and gas exchange. AB - To investigate the relationship between hypoxic pulmonary vasoconstriction and respiratory and metabolic acidosis and respiratory alkalosis, the pulmonary gas exchange and pulmonary hemodynamic responses were measured in anesthetized, paralyzed, and mechanically ventilated dogs in two sets of experiments (series A, n = 6; series B, n = 10). The animals were treated with acute hypoxia, CO2 inhalation, hyperventilation, and dinitrophenol in various combinations. Multiple regression analysis indicated that mean pulmonary arterial pressure (Ppa) was significantly correlated with end-tidal PO2, mixed venous PO2, and the mean pulmonary capillary pH (average of arterial and mixed venous pH) as independent variables [series A: r = +0.999, standard error of estimate (SEE) = 0.4 mmHg; series B: r = +0.98, SEE = 1.4 mmHg]. Similar analyses of mean values published by other authors from an acute study on humans with exercise at sea level and simulated altitudes of 10,000 and 15,000 ft also indicated a good relationship (n = 14, r = +0.98, SEE = 2.1 mmHg). The mean data (n = 19) obtained in Operation Everest II at various exercise loads and simulated altitudes gave a correlation of r = +0.87, SEE = 6.1 mmHg. These empirical analyses suggest that variations in the rise of Ppa with hypoxia can be accounted for in vivo by the superimposed acid-base status. Furthermore, ventilation-perfusion inhomogeneity, as estimated in the dogs from end-tidal and arterial O2 and CO2 differences and assuming no true shunt or diffusion impairment, was highly correlated with Ppa and mean pulmonary capillary pH (r = +0.999 in series A, r = +0.77 in series B). The human data from the above studies also showed significant correlations between Ppa and directly measured ventilation-perfusion (standard deviation of perfusion obtained from inert gas measurements). These observations indicate that the beneficial effects of hyperventilation during hypoxia may be related to the marked alkalosis that serves to reduce Ppa and improve pulmonary gas exchange efficiency. PMID- 1601788 TI - Effect of nocturnal atrial demand cardiac pacing on diurnal hemodynamic patterns. AB - Heart rate (HR), stroke volume (SV), intra-arterial blood pressure, and central venous pressure were recorded on a beat-to-beat basis, 18 h/day (1800-1200 h the following day), for approximately 2 mo in four monkeys (Macaca mulatta). Cardiac output, left ventricular work, and total peripheral resistance were derived from these primary measurements. During the 1st mo we measured these parameters under control conditions, and during the 2nd mo the animals were studied while HR was paced by atrial demand pacing sufficient to prevent the normal nocturnal fall in HR (approximately 10 beats/min above the fastest hourly average rate recorded during the control condition). The main hypothesis of this study was that when HR is prevented from falling, SV, which normally does not fall overnight, would fall; this hypothesis was confirmed. In addition, we observed that, during the period of pacing, relative to the control period, SV was approximately 14% greater during the early evening and 4% lower during the early morning; total peripheral resistance was similar during the early evening but was 13% higher by morning. Throughout the night, systolic pressure was approximately 4% greater, diastolic pressure was 17% higher, central venous pressure was 43% greater, and left ventricular work was 27% higher. These findings show that when HR is prevented from falling overnight by atrial demand pacing, even to a relatively modest degree, there can be very significant sustained changes in cardiovascular function. PMID- 1601789 TI - Systematic nocturnal atrial demand pacing results in high-output heart failure. AB - Beat-to-beat parameters of heart rate (HR), intra-arterial blood pressure (BP), central venous pressure, and derived indexes of cardiac output and total peripheral resistance were recorded 18 h/day (from 1800 to 1200 h the following day) in four monkeys (Macaca mulatta) during 20 control days followed by 20 days of atrial demand pacing. The pacing rate was set at approximately 10 beats/min above the fastest hourly average HR recorded during the control period, i.e., sufficient to prevent the normal nocturnal fall in HR. Nocturnal pacing resulted in progressive weekly increases in central venous BP and arterial BP. Analyses of levels and diurnal trends in hemodynamic parameters and cardiac function curves across consecutive 5-day periods of nocturnal pacing revealed a hemodynamic pattern characteristic of high-output heart failure, which progressively increased (week by week) during the early morning hours (0500-0700). Sustained elevated left ventricular work resulting from the prevention of a nocturnal fall in HR may have been responsible for the reduction in cardiac function seen in this experimental model. PMID- 1601790 TI - Oxygen cost of exercise hyperpnea: measurement. AB - To quantitate the O2 cost of maximal exercise hyperpnea, we required eight healthy adult subjects to mimic, at rest, the important mechanical components of submaximal and maximal exercise hyperpnea. Expired minute ventilation (VE), transpulmonary and transdiaphragmatic (Pdi) pressures, and end-expiratory lung volume (EELV) were measured during exercise at 70 and 100% of maximal O2 uptake. At rest, subjects were given visual feedback of their exercise transpulmonary pressure-tidal volume loop (WV), breathing frequency, and EELV, which they mimicked repeatedly for 5 min per trial over several trials, while hypocapnia was prevented. The change in total body O2 uptake (VO2) was measured and presumed to represent the O2 cost of the hyperpnea. In 61 mimicking trials with VE of 115-167 l/min and WV of 124-544 J/min, VE, WV, duty cycle of the breath, and expiratory gastric pressure (Pga) integrated with respect to time (integral of Pga.dt/min) were not different from those observed during maximum exercise. integral of Pdi.dt/min was 14% less and EELV was 6% greater during maximum exercise than during mimicking. The O2 cost measurements within a subject were reproducible over 3-12 trials (coefficient of variation +/- 10% range 5-16%). The O2 costs of hyperpnea correlated highly and positively with VE and WV and less, but significantly, with integral of Pdi.dt and integral of Pga.dt. The O2 cost of VE rose out of proportion to the increasing hyperpnea, so that between 70 and 100% of maximal VO2 delta VO2/delta VE increased 40-60% (1.8 +/- 0.2 to 2.9 +/- 0.1 ml O2/l VE) as VE doubled.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601791 TI - Oxygen cost of exercise hyperpnea: implications for performance. AB - We addressed two questions concerned with the metabolic cost and performance of respiratory muscles in healthy young subjects during exercise: 1) does exercise hyperpnea ever attain a "critical useful level"? and 2) is the work of breathing (WV) at maximum O2 uptake (VO2max) fatiguing to the respiratory muscles? During progressive exercise to maximum, we measured tidal expiratory flow-volume and transpulmonary pressure- (Ptp) volume loops. At rest, subjects mimicked their maximum and moderate exercise Ptp-volume loops, and we measured the O2 cost of the hyperpnea (VO2RM) and the length of time subjects could maintain reproduction of their maximum exercise loop. At maximum exercise, the O2 cost of ventilation (VE) averaged 10 +/- 0.7% of the VO2max. In subjects who used most of their maximum reserve for expiratory flow and for inspiratory muscle pressure development during maximum exercise, the VO2RM required 13-15% of VO2max. The O2 cost of increasing VE from one work rate to the next rose from 8% of the increase in total body VO2 (VO2T) during moderate exercise to 39 +/- 10% in the transition from heavy to maximum exercise; but in only one case of extreme hyperventilation, combined with a plateauing of the VO2T, did the increase in VO2RM equal the increase in VO2T. All subjects were able to voluntarily mimic maximum exercise WV for 3-10 times longer than the duration of the maximum exercise. We conclude that the O2 cost of exercise hyperpnea is a significant fraction of the total VO2max but is not sufficient to cause a critical level of "useful" hyperpnea to be achieved in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601792 TI - Effect of blood flow on net lactate uptake during steady-level contractions in canine skeletal muscle. AB - The purpose of this study was to determine the effect of blood flow on net lactate uptake (L) at constant elevated blood lactate concentration and metabolic rate in the in situ dog gastrocnemius-plantaris (GP) muscle. In all experiments, an infusion of lactate/lactic acid at a pH of 3.8 established a blood lactate concentration of 10-13 mM while maintaining normal blood gas/pH status as the GP was stimulated to contract with twitches at 1 Hz. In series 1 (n = 14), blood flow (ml.kg-1.min-1) was controlled by a pump at either 1) the spontaneous level for 1-Hz contractions (control flow = 332 +/- 23) or 2) a level estimated to be approximately 65% greater (high flow = 543 +/- 42). In series 2 (n = 7), perfusion pressure was varied during 1-Hz contractions. Four different perfusion pressures (80, 120, 155, and 180 Torr) were presented to each GP preparation, resulting in mean flow rates of 308 +/- 34, 419 +/- 30, 492 +/- 37, and 646 +/- 30 ml.kg-1.min-1. Increasing blood flow had no significant effect on net L in series 1. Similarly, there was no significant change in net L across the first three perfusion pressures/flow rates in series 2. However, net L (mmol.kg-1.min 1) was significantly increased in the highest perfusion pressure/flow rate period (from 0.335 +/- 0.029 at 80 Torr to 0.431 +/- 0.034 at 180 Torr). This study suggests that blood flow may have an independent effect on net L at the upper extreme of the normal blood flow range during contractions but very little effect over a fairly wide low-to-middle range of flow rates. PMID- 1601793 TI - Capillary perfusion patterns in single alveolar walls. AB - We studied capillary perfusion patterns in single alveolar walls through a transparent thoracic window implanted in pentobarbital-anesthetized dogs. The capillaries were maximally opened by brief inflation of a balloon in the left atrium to raise pressure. After the balloon was deflated and pulmonary hemodynamics returned to zone 2 baseline conditions, the capillaries that remained perfused in the observed field were videotaped with the use of in vivo microscopy. The cycle of elevated pressure and baseline observation was repeated three times. Perfusion of different capillaries during each of the observations would imply that the capillaries had characteristics that permitted flow to switch between segments. Perfusion of a specific set of pathways through the network each time would demonstrate that flowing blood sought a unique and repeatable combination of segments, presumably with the least total pathway resistance. We found that the same capillary segments were perfused 79% of the time, a strong indication that a reproducible combination of individual segmental resistances determined the predominant pattern of pulmonary capillary perfusion. PMID- 1601794 TI - Carbohydrate-protein complex increases the rate of muscle glycogen storage after exercise. AB - Carbohydrate, protein, and carbohydrate-protein supplements were compared to determine their effects on muscle glycogen storage during recovery from prolonged exhaustive exercise. Nine male subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after each exercise bout, they ingested 112.0 g carbohydrate (CHO), 40.7 g protein (PRO), or 112.0 g carbohydrate and 40.7 g protein (CHO-PRO). Blood samples were drawn before exercise, immediately after exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately and 4 h after exercise. During recovery the plasma glucose response of the CHO treatment was significantly greater than that of the CHO-PRO treatment, but the plasma insulin response of the CHO-PRO treatment was significantly greater than that of the CHO treatment. Both the CHO and CHO-PRO treatments produced plasma glucose and insulin responses that were greater than those produced by the PRO treatment (P less than 0.05). The rate of muscle glycogen storage during the CHO-PRO treatment [35.5 +/- 3.3 (SE) mumol.g protein-1.h-1] was significantly faster than during the CHO treatment (25.6 +/- 2.3 mumol.g protein-1.h-1), which was significantly faster than during the PRO treatment (7.6 +/- 1.4 mumol.g protein-1.h-1). The results suggest that postexercise muscle glycogen storage can be enhanced with a carbohydrate-protein supplement as a result of the interaction of carbohydrate and protein on insulin secretion. PMID- 1601795 TI - Is flow in subpleural region typical of the rest of the lung? A study using laser Doppler flowmetry. AB - The microcirculation in the subpleural region of the lung is thought to be physiologically typical of the entire vasculature. To investigate this issue, an in situ blood-perfused dog lung lobe (500 ml/min) was prepared and the blood flow in the subpleural region (Qs) was monitored with laser-Doppler flowmetry (LDF). The flow rates into and out of the lobe were monitored with in-line flow probes, and the arterial and venous pressures were recorded from side ports in the cannulas. The LDF signal measures flow in arbitrary units over a region less than 2 mm deep and 1 mm2. The LDF signal was independent of site of measurement and was linearly proportional to total flow rate (r2 greater than 0.9), suggesting that during baseline conditions Qs behaves similarly to, although not necessarily the same as, blood flow in the rest of the lung. However, if the vasculature is constricted by serotonin (arterial constriction) or by histamine (venous constriction), Qs decreases significantly relative to total flow. In fact, in some cases Qs approached zero during vasoconstriction, despite the fact that total flow was maintained constant and the pulmonary arterial pressure became elevated. Reduction in Qs most likely reflects a redistribution from the subpleural to the central regions of the lung. The results of this study suggest that LDF is a useful tool for monitoring flow in the subpleural region of the lung.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601796 TI - Effect of leg exercise training on vascular volumes during 30 days of 6 degrees head-down bed rest. AB - Plasma and red cell volumes, body density, and water balance were measured in 19 men (32-42 yr) confined to bed rest (BR). One group (n = 5) had no exercise training (NOE), another near-maximal variable-intensity isotonic exercise for 60 min/day (ITE; n = 7), and the third near-maximal intermittent isokinetic exercise for 60 min/day (IKE; n = 7). Caloric intake was 2,678-2,840 kcal/day; mean body weight (n = 19) decreased by 0.58 +/- 0.35 (SE) kg during BR due to a negative fluid balance (diuresis) on day 1. Mean energy costs for the NOE, and IKE, and ITE regimens were 83 (3.6 +/- 0.2 ml O2.min-1.kg-1), 214 (8.9 +/- 0.5 ml.min-1.kg 1), and 446 kcal/h (18.8 +/- 1.6 ml.min-1.kg-1), respectively. Body densities within groups and mean urine volumes (1,752-1,846 ml/day) between groups were unchanged during BR. Resting changes in plasma volume (ml/kg) after BR were -1.5 +/- 2.3% (NS) in ITE, -14.7 +/- 2.8% (P less than 0.05) in NOE, and -16.8 +/- 2.9% (P less than 0.05) in IKE, and mean water balances during BR were +295, 106, and +169 ml/24 h, respectively. Changes in red cell volume followed changes in plasma volume. The significant chronic decreases in plasma volume in the IKE and NOE groups and its maintenance in the ITE group could not be accounted for by water balance or by responses of the plasma osmotic, protein, vasopressin, or aldosterone concentrations or plasma renin activity. There was close coupling between resting plasma volume and plasma protein and osmotic content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601797 TI - Role of tissue hypoxia as the mechanism of lactic acidosis during E. coli endotoxemia. AB - We compared the hemodynamic and metabolic alterations produced in rabbits by similar decreases in cardiac output created by inflating a balloon placed in the right ventricle (n = 6) with those produced by an intravenous bolus of Escherichia coli lipopolysaccharide (LPS; SEP group; n = 6). We measured O2 consumption (VO2), O2 transport (TO2), and O2 extraction ratio (ERO2) for the whole animal and also for the left hindlimb. Both groups experienced similar decreases in cardiac output, systemic TO2, and VO2 and similar increases in ERO2. For the hindlimb, TO2 was similar, but VO2 and ERO2 were lower for the SEP group 30 min after LPS administration (P less than 0.05); however, this difference disappeared during the remainder of the experiment. Arterial lactate concentration was greater (P less than 0.05) for the SEP group. There were no differences in skeletal muscle PO2, measured with a multiwire surface electrode, or in cardiac and skeletal muscle concentrations of high-energy phosphates. We hypothesize that a direct effect of LPS on cellular metabolism may have resulted in greater arterial lactate concentration for the SEP group. PMID- 1601798 TI - Role of tumor necrosis factor in oxygen toxicity. AB - mRNA from lungs of mice exposed to high-dose oxygen (greater than 95%) for 3 days demonstrated increased expression of the genes for tumor necrosis factor (TNF), interleukin-1, and interleukin-6 compared with mRNA from lungs of mice exposed to room air. Daily treatment of mice exposed to high-dose oxygen with an antibody to TNF improved survival compared with mice receiving a similar dose of control immunoglobulin G. Pretreatment of mice with repetitive sublethal intraperitoneal doses of recombinant human TNF for 3 days or a single intravenous dose followed by exposure to high-dose oxygen afforded a significant survival advantage compared with high-dose oxygen-exposed mice pretreated with vehicle or interleukin-1. The repetitive intraperitoneal TNF pretreatment reduced the development of interstitial pneumonitis, pulmonary edema, and lung weight gain associated with oxygen toxicity and enhanced expression of the gene for the free radical protective enzyme manganous superoxide dismutase in lung tissue, a gene that is augmented as mice are exposed to high-dose oxygen. Furthermore a single intravenous dose of TNF 24 h after oxygen exposure was still protective. The results suggest that the toxicity of oxygen therapy can be partially ameliorated by either treatment with anti-TNF antibody or pretreatment and early treatment with TNF. These findings are consistent with the hypothesis that oxygen exposure induces TNF, which causes part of the toxicity of high-dose oxygen, and that pretreatment or early treatment with TNF induces the gene for an enzyme that recently has been shown to be very effective in protecting mice from the toxicity of oxygen. PMID- 1601799 TI - Muscle sounds during voluntary and stimulated contractions of the human adductor pollicis muscle. AB - The relationships between force, electromyography (EMG), and muscle sounds recorded by acoustic myography (AMG) were investigated for both voluntary and stimulated isometric contractions in the adductor pollicis muscle. Voluntary activity was performed at 10, 25, 50, 75, 85, and 100% of maximal voluntary contraction (MVC) force. Stimulated contractions were produced by supramaximal electrical stimulation of the ulnar nerve at the wrist at frequencies of 10, 20, 30, 50, 70, and 100 Hz. Contractions lasted for 4 s each, and were performed in random order with a 3-min rest between each. The voluntary and stimulation studies were performed in random order between subjects. Simultaneous recordings were obtained for force, force oscillation (from the differentiated force signal), and raw and integrated AMG (IAMG) and EMG (IEMG). During voluntary contractions, IAMG increased with force up to MVC (r2 = 0.99, P less than 0.001) in a curvilinear fashion and a similar relationship was seen between force and IEMG (r2 = 0.99, P less than 0.001). Conversely, during stimulated contractions as stimulation frequency increased, IAMG decreased in a fashion mirroring the frequency-force curve. The frequency of the AMG signal matched stimulation frequency and declines in total IAMG were due to reductions in amplitude of the AMG signal. The stimulation frequency-oscillation of force relationship was identical to that seen for stimulation frequency and IAMG. Integrated EMG increased linearly with stimulation frequency (r = 0.99). The stimulation results suggest that muscle sounds reflect oscillation of muscle fibers and that AMG signal characteristics are determined by motor control mechanisms rather than intrinsic contractile processes. PMID- 1601800 TI - alpha-Difluoromethylornithine attenuates monocrotaline-induced airway/lung dysfunction. AB - On the basis of the previous findings that alpha-difluoromethylornithine (DFMO, an inhibitor of ornithine decarboxylase, which is the rate-limiting enzyme in polyamine biosynthesis) treatment prevents monocrotaline-(MCT) induced pulmonary hypertension and that ventilatory dysfunction precedes pulmonary hypertension in MCT-treated rats, we hypothesize that MCT-induced changes in airway/lung function are polyamine dependent. To evaluate this hypothesis, in phase 1, 48 young Sprague-Dawley rats were evenly divided into four groups: control, DFMO, MCT, and DFMO + MCT. Each DFMO rat received DFMO in its drinking water (2%) for 11 days, with additional injections (400 mg/kg sc) on the 5th day. Each MCT rat received a single injection of MCT (60 mg/kg sc) 1 wk before the functional study. Each DFMO + MCT rat received the same DFMO and MCT treatments as above, and MCT was administered on the 5th day of the DFMO treatment. In the MCT group, there were marked rightward shifts in pressure-volume and maximal flow-static recoil (MFSR) curves and significant decreases in dynamic and quasi-static compliance, the maximal expiratory flow, slope of the MFSR curve, and the carbon monoxide diffusing capacity, as well as a significant increase in alveolar wall thickness. However, in rats treated with DFMO + MCT, most of MCT-induced changes were significantly attenuated. To evaluate whether MCT causes bronchoconstriction, a bronchodilator, terbutaline (0.2 mg/kg i.v.), was administered to control (n = 7) and MCT (n = 11) rats in phase 2. Terbutaline significantly reversed MCT-induced decreases in maximal expiratory flow and slope of the MFSR curve, whereas it did not alter these parameters in controls.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601801 TI - Locomotion in men has no appreciable mechanical effect on breathing. AB - It has been suggested that the act of taking a stride produces substantial respiratory volume displacement and that this assists the respiratory muscles during locomotion. We measured the flow at the mouth associated with stride in walking and running humans and found it to be 1-2% of respiratory tidal volume, which is too small to make an appreciable contribution to pulmonary ventilation. PMID- 1601803 TI - Intercostal muscles are used during rotation of the thorax in humans. AB - To test the idea that the lateral intercostal muscles may be more suited to aid in rotational than respiratory movements of the thorax, we inserted bipolar fine wire electrodes in external and internal intercostal muscles in the right midaxillary line in nine sitting subjects and examined the pattern of contraction of these muscles during voluntary axial rotations of the thorax (30-35 degrees), resting breathing, and CO2-induced hyperpnea. The right external intercostal muscles were strongly recruited in rotations to the left but were not active in rotations to the right. In contrast, the right internal intercostal muscles were active in rotations to the right but not in rotations to the left. Rotations completed in 1 or 2 s were associated with an early burst of electromyographic activity, followed by a low plateau that persisted while the rotation was held. Rotations made very gradually over 5-10 s were associated with gradually rising electromyographic activity. The amplitude of activity recorded during 30-35 degrees rotations was equivalent to that measured when minute ventilation was increased by CO2 to 50 l/min. We conclude that the lateral intercostal muscles have a major role in producing axial rotations of the thorax. PMID- 1601802 TI - Aerosolized Pseudomonas elastase and lung fluid balance in anesthetized sheep. AB - The role of the lung epithelium in lung fluid balance was studied by ventilating anesthetized sheep with an aerosol of 20 mg of elastase from Pseudomonas aeruginosa (Ps. elastase) to increase lung epithelial permeability without affecting lung endothelial permeability or lung vascular pressures. Ps. elastase had no effect on the lung vascular pressures, the alveolar-arterial PO2 gradient (A-aPO2), the flow or protein concentration of the lung lymph, or the postmortem water volume of the lungs. The morphological alveolar flooding score in these sheep was 2.5 times the control level, but this was only marginally significant. Elevation of the left atrial pressure by 20 cmH2O alone increased the postmortem lung water volume but had no effect on A-aPO2, the alveolar flooding score, or the lung epithelial permeability assessed by the clearance of 99mTc-labeled human serum albumin. Addition of aerosolized Ps. elastase to these sheep had no effect on the total lung water volume, but it caused a redistribution of water into the air spaces, as evidenced by significant increases in the alveolar flooding score and A-aPO2 (P less than 0.01). Elevation of the left atrial pressure by 40 cmH2O without elastase caused the same response as elevation of the left atrial pressure by 20 cmH2O with elastase, except the higher pressure caused a greater increase in the total lung water volume. We conclude that alteration of the integrity of the lung epithelium with aerosolized Ps. elastase causes a redistribution of lung water into the alveoli without affecting the total lung water volume.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601804 TI - Effects of haloperidol and domperidone on ventilatory roll off during sustained hypoxia in cats. AB - In a previous work, we showed that the adult cat demonstrates a ventilatory decline during sustained hypoxia (the "roll off" phenomenon) and that the mechanism responsible for this secondary decrease in ventilation lies within the central nervous system (J. Appl. Physiol. 63: 1658-1664, 1987). In this study, we sought to determine whether central dopaminergic mechanisms could have a role in the roll off. We studied the effects of haloperidol, a peripheral and centrally acting dopamine receptor antagonist, on the ventilatory response to sustained isocapnic hypoxia (end-tidal PO2 40-50 Torr, 20-25 min) in awake cats. In vehicle control cats (n = 5), sustained hypoxia elicited a biphasic respiratory response, during which an initial ventilatory stimulation is followed by a 24 +/- 6% (P less than 0.01) reduction. In contrast, in haloperidol- (0.1 mg/kg) treated cats (n = 5) the ventilatory roll off was virtually abolished (-1 +/- 1%; P = NS). We also measured ventilatory, carotid sinus nerve (CSN) and phrenic nerve (PhN) responses to sustained isocapnic hypoxia in anesthetized animals (n = 6) to explore the influence of haloperidol on peripheral and central response during the roll off. Control responses to hypoxia showed an initial increase in ventilation, PhN, and CSN activity, followed by a subsequent decline in ventilation and PhN activity of 17 +/- 3 and 17 +/- 5%, respectively (P less than 0.05). In contrast, CSN activity remained unchanged during the roll off. Administration of haloperidol (1 mg/kg) reduced the initial increment in ventilation, while the initial increase in CSN activity was augmented.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601806 TI - Aging and physical activity determine cardiac structure and function in the older athlete. AB - To evaluate the effects of age and physical activity on cardiac structure and function, 45 ultra-endurance athletes were compared with 24 sedentary control subjects. Two-dimensionally guided M-mode echocardiograms and pulsed Doppler studies of left ventricular inflow velocity were obtained. Both older and younger athletes differed from age-similar sedentary control subjects in having lower heart rates (56 vs. 72 beats/min, younger; 53 vs. 74 beats/min, older), larger left ventricular cavities at end diastole (5.4 vs. 4.9 cm younger; 5.4 vs. 4.9 cm older), and higher ratios of early to atrial inflow velocities (2.14 vs. 1.37, younger; 1.32 vs. 0.83, older; all P less than 0.05). Older athletes differed from younger athletes in having higher systolic and diastolic blood pressures (131/79 vs. 122/71 mmHg), greater posterior wall thickness (1.1 vs. 0.9 cm), lower rapid filling velocity (52 vs. 70 cm/s), higher atrial systolic velocity (41 vs. 34 cm/s), and lower early-to-atrial inflow velocity ratios (1.32 vs. 2.14, all P less than 0.05). Thus the aging heart manifests structural and functional changes in response to physical activity that are similar but not identical to those seen in younger subjects. The expected pattern of cardiac alterations normally seen in response to age is modified in the older athlete, suggesting that exercise training, as well as aging, is an effective stimulus in shaping left ventricular structure and function in the older heart. PMID- 1601805 TI - New perfluorocarbon emulsion improves tissue oxygenation in cat retina. AB - We have studied the conditions under which a perfluorocarbon emulsion of perfluorooctyl bromide (PFOB; Alliance Pharmaceutical, San Diego, CA) enhances tissue O2 delivery. Measurements of retinal tissue O2 tension (PO2) were made in anesthetized, artificially respirated, dark-adapted, normovolemic cats before, during, and after the infusion of three successive doses of 1 g PFOB/kg body wt each. There was little immediate effect of the infusion on the tissue PO2 when the cats were breathing room air, but the mean increase in tissue PO2 during 100% O2 breathing was 60 +/- 9% (SE; n = 8 cats) greater after infusion of 1 g PFOB/kg and approximately 136% greater after 3 g PFOB/kg. Similar infusions of the emulsifying medium alone had negligible effects on tissue PO2. These results suggest that PFOB emulsion may be clinically useful in treating tissue hypoxia in normovolemic patients breathing O2-enriched air. PMID- 1601807 TI - Finger-specific flexor recruitment in humans: depiction by exercise-enhanced MRI. AB - To evaluate the spatial distribution of human forearm musculature stressed by finger-specific exercise, magnetic resonance imaging was performed in conjunction with exercise protocols designed to separately stress the flexor digitorum superficialis and flexor digitorum profundus. These muscles were shown to consist of subvolumes selectively recruited by flexion of the individual fingers. Knowledge of the finger-specific regions of muscle recruitment during finger flexion could improve sampling accuracy in electromyography, biopsy, magnetic resonance spectroscopy, and invasive vascular sampling studies of hand exercise. PMID- 1601809 TI - Effects of longitudinal laparotomy on respiratory system, lung, and chest wall mechanics. AB - In six sedated, anesthetized, paralyzed, and mechanically ventilated guinea pigs, total respiratory system (RT,rs), lung, and chest wall resistances and respiratory system (Est,rs), lung, and chest wall (Est,w) elastances were determined before and after longitudinal laparotomy. Furthermore the resistances were also split into their initial and difference components, with the former reflecting the Newtonian resistances and the latter representing the viscoelastic/inhomogeneous pressure dissipations in the system. For such purpose the end-inflation occlusion during constant inspiratory flow method was used. During laparotomy, a statistically significant increase in respiratory system difference resistance (from 0.086 to 0.101 cmH2O.ml-1.s) significantly augmented RT,rs (from 0.157 to 0.167 cmH2O.ml-1.s). The former was entirely secondary to a significant increase in chest wall difference resistance (0.019 to 0.034 cmH2O.ml 1.s), which naturally raised chest wall total resistance (from 0.030 to 0.047 cmH2O.ml-1.s). Est,rs and Est,w also increased (14.7 and 13.1%, respectively) after abdominal incision. It can be concluded that the midline xiphipubic laparotomy accompanied by the bilateral ventrodorsal infracostal incision increases RT,rs as a consequence of augmented chest wall difference resistance and Est,rs as a result of higher Est,w. PMID- 1601808 TI - Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea. AB - We have described a rat model that responds to repetitive episodic hypoxia (12-s infusions of nitrogen into daytime sleeping chambers every 30 s, 7 h/day for 35 days) with an increase in diurnal systemic blood pressure. We hypothesized that afferent information from the peripheral chemoreceptors may be necessary to produce diurnal blood pressure elevation in this hypoxia model. Carotid body denervation (CBD) was accomplished by severing both carotid sinus nerves in two groups of male Wistar rats (250-375 g). Group 4 CBD rats were subjected to intermittent hypoxia for 35 days (3-5% nadir ambient O2) as described above, whereas group 5 CBD rats remained unhandled in their usual cages. Additional sham operated controls included group 2 sham-"hypoxia" rats, which were housed in chambers identical to the hypoxia rats but supplied with compressed air instead of nitrogen, group 1 (not denervated) rats, which remained unhandled in their usual cages, and group 3 sham-operated rats, which were subjected to 35 days of intermittent hypoxia identical to group 4 CBD rats. Femoral arterial baseline and end-of-study blood pressures were measured in conscious rats. The group 3 rats exposed to episodic hypoxia displayed a 13-mmHg increase in mean blood pressure, whereas the other groups showed no significant change from baseline. Left ventricular hypertrophy was evident in all rats exposed to episodic hypoxia, but right ventricular hypertrophy was evident only in the group 4 rats. All CBD rats developed increased hematocrit and hemoglobin, while the group 3 rats (non-CBD, episodic hypoxia) did not. The baroreceptor reflex at baseline was not depressed in the CBD rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601810 TI - Insulin-induced hypoglycemia in fed and fasted exercising rats. AB - To determine running performance and hormonal and metabolic responses during insulin-induced hypoglycemia, fed and fasted male rats (315 +/- 3 g) were infused with insulin (100 mU/ml, 1.5 ml/h) or saline (1.5 ml/h) for 60 min and then killed at rest or after running on the treadmill (21 m/min, 15% grade). Insulin infused fed rats ran poorly during the second 10 min of a 20-min exercise test. They were capable of running a total of 43 +/- 5 min, compared with 138 +/- 6 min for saline-infused fed rats. Fasted insulin-infused rats were able to run only 12.8 +/- 0.8 min, compared with 122 +/- 15 min for fasted saline-infused rats. In fasted rats, blood glucose was 1.6 +/- 0.1 mM after 60 min of insulin infusion and 1.2 +/- 0.1 mM after running to exhaustion. Artificial increase of plasma free fatty acids had no effect on performance. Intravenous infusion of glucose at the time of fatigue produced an immediate recovery, allowing the formerly fatigued rats to run 20 min without development of fatigue. These results provide evidence that severe hypoglycemia can be a significant cause of fatigue, even if it occurs early in the course of an exercise bout. PMID- 1601811 TI - Time course of glycogen accumulation after eccentric exercise. AB - This study examined the time course of glycogen accumulation in skeletal muscle depleted by concentric work and subsequently subjected to eccentric exercise. Eight men exercised to exhaustion on a cycle ergometer [70% of maximal O2 consumption (VO2max)] and were placed on a carbohydrate-restricted diet. Approximately 12 h later they exercised one leg to subjective failure by repeated eccentric action of the knee extensors against a resistance equal to 120% of their one-repetition maximum concentric knee extension force (ECC leg). The contralateral leg was not exercised and served as a control (CON leg). During the 72-h recovery period, subjects consumed 7 g carbohydrate.kg body wt-1.day-1. Moderate soreness was experienced in the ECC leg 24-72 h after eccentric exercise. Muscle biopsies from the vastus lateralis of the ECC and CON legs revealed similar glycogen levels immediately after eccentric exercise (40.2 +/- 5.2 and 47.6 +/- 6.4 mmol/kg wet wt, respectively; P greater than 0.05). There was no difference in the glycogen content of ECC and CON legs after 6 h of recovery (77.7 +/- 7.9 and 85.1 +/- 4.9 mmol/kg wet wt, respectively; P greater than 0.05), but 18 h later, the ECC leg contained 15% less glycogen than the CON leg (90.2 +/- 8.2 vs. 105.8 +/- 8.9 mmol/kg wet wt; P less than 0.05). After 72 h of recovery, this difference had increased to 24% (115.8 +/- 8.0 vs. 153.0 +/- 12.2 mmol/kg wet wt; P less than 0.05). These data confirm that glycogen accumulation is impaired in eccentrically exercised muscle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601812 TI - Optimization character of inspiratory neural drive. AB - A previous optimal chemical-mechanical model (C.-S. Poon. J. Appl. Physiol. 62: 2447-2459, 1987) suggested that the normal ventilatory responses to CO2 and exercise inputs and mechanical loading can be predicted by the minimization of a controller objective function consisting of the total chemical and mechanical costs of breathing. In this study the model was generalized to include a description of the inspiratory neuromuscular drive as the control output. With a mechanical work rate index for both inspiration and expiration, the general optimization model accurately reproduced the observed responses in the waveshape of inspiratory drive, breathing pattern, and total ventilation under differing conditions of CO2 inhalation, exercise, and inspiratory/expiratory mechanical loads. The simulation results are in general agreement with a wide range of respiratory phenomena, including exercise hyperpnea, CO2 chemoreflex, and post inspiratory (postinflow) inspiratory activity, as well as respiratory neural compensations for mechanical loading, respiratory muscle fatigue, and muscle weakness. PMID- 1601813 TI - Rapid onset of hypoxic vasoconstriction in isolated lungs. AB - A fast-response O2 analyzer that samples air at low flow rates allows the quasi instantaneous measurement of O2 concentration change in the airways of isolated blood-perfused rat lungs. This instrument and an oximeter were used to measure the stimulus-response delay time of hypoxic pulmonary vasoconstriction when the lungs were challenged with 10, 5, or 3% O2. The estimate for the shortest delay time between accomplished fall in airway O2 concentration and the onset of hypoxia-induced vasoconstriction was approximately 7 s. We found that the slope of pressure rise, but not the stimulus-response delay time, correlated with the magnitude of hypoxic vasoconstriction. Oscillations in pulmonary arterial pressure were observed when the lungs were challenged with 10% O2 but not when the challenge was 12, 5, or 3%, indicating perhaps that these oscillations were a threshold phenomenon. Established hypoxic vasoconstriction was sensitive to brief changes in airway O2 concentration. Vasodilation occurred when the gas mixture was switched from 3 to 21% O2 for two to five breaths, and vasoconstriction occurred when the gas was changed during a single breath from 5 to 3% O2. PMID- 1601814 TI - Predictability of ventilatory muscle optimal length based on excised dimensions. AB - The purpose of the present study was to assess the relationship between excised length (unstressed length of excised muscle; Lex) and optimal force-generating length (Lo) in a variety of respiratory muscles, with the goal of establishing a reliable method whereby Lo could be rapidly and easily estimated with a high level of accuracy. Experiments were conducted on 111 muscle bundles obtained from 18 mongrel dogs. Segments of costal diaphragm, parasternal intercostal, scalene, sternomastoid, triangularis sterni, rectus abdominis, external oblique, and transversus abdominis muscles were studied. We noted a linear relationship between the distance measured between two fixed points in excised bundles (Lex) and at the muscles' Lo. Correlation coefficients ranged from 0.83 (P less than 0.01) for the transversus abdominis to 0.92 (P less than 0.01) for the triangularis sterni and external oblique muscles. Pooled Lex for all muscles averaged 61.4 +/- 6.3% (SD) Lo, with specific values ranging from 55.5 +/- 3.9% Lo for triangularis sterni bundles to 63.0 +/- 5.1% Lo for external oblique bundles. In three additional dogs, we verified the usefulness of this relationship and prospectively estimated Lo from excised length in 10 costal diaphragm bundles and 10 transversus abdominis bundles and then measured Lo directly. Predicted Lo averaged 100.0 +/- 6.0% Lo for diaphragm and 97.6 +/- 5.9% Lo for transversus abdominis muscle. We conclude that Lo can be conveniently and accurately estimated from excised dimensions. This rapid estimation technique should prove valuable for future studies in respiratory muscle physiology. PMID- 1601815 TI - Simple computer measurement of pulmonary VCO2 per breath. AB - Measurements of the volume of CO2 exhaled per breath (VCO2/br) are preferable to end-tidal PCO2, when the exhaled flow and CO2 waveforms may be changing during unsteady states, such as during alterations in positive end-expiratory pressure or alterations in cardiac output. We describe computer algorithms that determine VCO2/br from digital measurements of exhaled flow (including discontinuous signals common in anesthesia circuits) and CO2 concentration at the airway opening. Fractional concentration of CO2 is normally corrected for dynamic response and transport delay (TD), measured in a separate procedure. Instead, we determine an on-line adjusted TD during baseline ventilation. In six anesthetized dogs, we compared the determination of VCO2/br with a value measured in a simultaneous collection of expired gas. Over a wide range of tidal volume (180 700 ml), respiratory rate (3-30 min-1), and positive end-expiratory pressure (0 14 cmH2O), VCO2/br was more accurate with use of the adjusted TD than the measured TD (P less than 0.05). PMID- 1601816 TI - Effects of left atrial pressure on the pulmonary vascular response to hypoxic ventilation. PMID- 1601817 TI - Dynamic performance of a load-moving skeletal muscle. PMID- 1601818 TI - Disseminated intravascular coagulation syndromes. AB - Current concepts of the etiology, pathophysiology, diagnosis, and management of fulminant as well as low-grade disseminated intravascular coagulation have been presented. Considerable attention has been devoted to interrelationships within the hemostasis system. Only by clearly understanding these pathophysiological interrelationships can the clinician and laboratory scientists appreciate the divergent and wide spectrum of often confusing clinical and laboratory findings in patients with disseminated intravascular coagulation. Many therapeutic decisions to be made in these patients are controversial and will remain so until more series of patients are published concerning specific therapeutic modalities and survival patterns. In addition, therapy must be highly individualized depending upon the nature of DIC, age, etiology of DIC, site and severity of hemorrhage or thrombosis and hemodynamic and other clinical parameters. Many syndromes which are organ specific share common pathophysiology with disseminated intravascular coagulation but are typically identified as an independent disease entity, such as hemolytic uremic syndrome, adult shock lung syndrome, eclampsia, and many other isolated "organ-specific" disorders. PMID- 1601819 TI - Chromosome observations of acute promyelocytic leukemia treated with all-trans retinoic acid. AB - Chromosome changes were observed in 8 patients with acute promyelocytic leukemia during the all-trans retinoic acid-induced differentiation course. Karyotype of patient bone marrow specimens after short-term incubation were analyzed using Giemsa-R banding. Analyses showed all 8 patients had the abnormal translocation between chromosomes 15 and 17, but when those patients were treated with all trans retinoic acid and were in remission, the characteristic t(15;17) chromosomal abnormality disappeared. However, this aberration of chromosomes detected in 3 patients persisted during the early period of RA induction, although the patients could still achieve complete remission. However, it was found that the percentage of abnormal karyotypes declined during this early period. This phenomenon may be an important indicator for clinical remission. When one case relapsed, the t(15;17) reappeared. Thus the chromosome t(15;17) was not only useful in diagnosis, but also helpful in observing prognosis in acute promyelocytic leukemia. PMID- 1601820 TI - Laboratory evidence in support of the currently recommended therapeutic ratio for oral anticoagulant therapy. PMID- 1601821 TI - Reactivity of monoclonal antibody B-ly7 with a subset of activated T cells and T cell lymphomas. AB - Antibody B-ly7 is reactive with hairy cell leukemia and a small subpopulation of normal lymphocytes. The B-ly7 antigen can also be induced on normal peripheral blood lymphocytes by phorbol ester stimulation. Recently it has been found that the reactivity pattern of B-ly7 is similar to that of HML-1, an antibody reactive with mucosal T lymphocytes and so called enteropathy associated T-cell lymphomas. Reactivity of B-ly7 with 6/61 peripheral T-cell lymphomas, including two intestinal and four extraintestinal cases, is described. The intestinal cases were CD8 and CD7 positive, whereas the extraintestinal cases were CD4 positive and CD7 negative. Activation of purified peripheral blood T cells resulted in approximately 20% B-ly7+ T cells at Day 3. Approximately 75% of the B-ly7+ cells were CD8+, whereas the remainder were CD4+. The results indicate that B-ly7 as well as HML-1 recognize an activation-associated antigen that is expressed on small normal T-cell and B-cell populations and can be induced on a relatively high proportion of T and B cells in vitro. PMID- 1601823 TI - Employee substance use and on-the-job behaviors. AB - Substance use and job behaviors were assessed in a sample of municipal employees from a large city in the southwestern United States. Job behaviors included psychological and physical withdrawal, positive work behaviors, and antagonistic work behaviors. Employees who reported substance use at or away from work were found to more frequently engage in withdrawal activities and antagonistic work behaviors than did nonusers, although users and nonusers did not differ on positive work behaviors. We tested hierarchical regression models to determine whether substance use contributed unique variance to the prediction of job behaviors after we controlled for variance associated with personal and job background domains. Substance use added unique variance to the prediction of psychological and physical withdrawal behaviors but not to positive or antagonistic work behaviors. PMID- 1601822 TI - AML-associated cytogenetic abnormalities (inv (16), del (16), t(8;21)) in patients with myelodysplastic syndromes. AB - Evidence suggests that prognosis in patients with myelodysplastic syndromes (MDS) or acute myelogenous leukemia (AML) depends more on karyotype than on formal classification as either MDS or AML according to the French-American-British (FAB) system. We provide further evidence of overlap between these two entities, reporting 4 patients who presented with either inv(16) (p13q22), del(16) (q22), or t(8;21) despite an FAB diagnosis of MDS rather than the diagnosis of AML with which these abnormalities are generally associated. In 3 patients, disease was relatively long-standing (3-10 months) prior to diagnosis, suggesting that the association between MDS and these cytogenetic abnormalities may not merely reflect a transient phenomenon. Two patients with inv(16) and the MDS subtype refractory anemia with excess blasts in transformation (RAEB-t) received AML-type chemotherapy as did a patient with t(8;21) and RAEB-t. All entered CR paralleling the high CR rate seen in patients with AML and these abnormalities. Our data support the concept that MDS and AML may be different manifestations of the same disease. PMID- 1601824 TI - Dispositional affect and work-related stress. AB - Trait negative affectivity (NA) has been asserted to be a factor that spuriously inflates relationships between self-reported stressors and self-reported strain outcomes. We tested this hypothesis with conventional work stress instrument responses and physiological assessments obtained from 311 fire and police department employees. Confirmatory factor analyses indicated that NA did not measure a factor in common with measures of subjective strain. Latent-variable structural equations analyses, however, found that estimating the effects of NA on strain significantly attenuated the effects of work stressors. NA had no correlation with physiological stress outcomes. Trait positive affectivity did not attenuate relationships between work stressors and either subjective or objective stress outcomes. Implications for work stress research methodology and recommendations are discussed. PMID- 1601825 TI - Moderated regression analysis and Likert scales: too coarse for comfort. AB - One of the most commonly accepted models of relationships among three variables in applied industrial and organizational psychology is the simple moderator effect. However, many authors have expressed concern over the general lack of empirical support for interaction effects reported in the literature. We demonstrate in the current sample that use of a continuous, dependent-response scale instead of a discrete, Likert-type scale, causes moderated regression analysis effect sizes to increase an average of 93%. We suggest that use of relatively coarse Likert scales to measure fine dependent responses causes information loss that, although varying widely across subjects, greatly reduces the probability of detecting true interaction effects. Specific recommendations for alternate research strategies are made. PMID- 1601826 TI - Inaccurate reporting and inappropriate variables: a reply to Vecchio's (1990) examination of cognitive resource theory. AB - In an article in the Journal of Applied Psychology, Vecchio (1990) purported to test cognitive resource theory (Fiedler, 1986; Fiedler & Garcia, 1987). We present evidence that Vecchio's article seriously misrepresented previous work on cognitive resource theory and also contained several flaws in methodology that call into question his conclusions regarding the validity of cognitive resource theory. PMID- 1601827 TI - 70% by '92. PMID- 1601828 TI - Involvement of Arkansas hospitals in promotion of car restraint device use among young children. AB - Child restraint devices are a proven means of reducing automobile-related deaths and injuries among infants and toddlers. To determine the role that Arkansas hospitals play in promoting use of these devices, a survey similar to one conducted previously in Tennessee was performed of hospitals providing newborn and/or pediatric services. Hospital policies relating to discharge of patients in car restraints were more likely to pertain to newborns than to older children. Nearly all the facilities having such policies claimed that these were strictly enforced. Hospitals are encouraged to establish discharge policies and to expand educational efforts and loaner programs. PMID- 1601829 TI - Phenomenological approach to the correct diagnosis of Parkinson's disease. AB - When dealing with movement disorders, it is helpful to first decide what phenomenon one is observing. Tremors can be differentiated from most other movement disorders and are further classified according to their frequency, and whether they are present at rest or with action. The parkinsonian syndrome can thus be identified correctly in most cases, and the etiology can usually be determined clinically. Correct diagnosis is the first step in correct treatment. PMID- 1601831 TI - Walking for fitness and fun. PMID- 1601830 TI - CHAR proposal makes state less fertile ground to recruit young smokers. PMID- 1601832 TI - Differences between medical decisions and moral judgments can injure patients and -sometimes lead to legal hassles. PMID- 1601833 TI - Radiological case of the month. What is the percent stenosis? PMID- 1601834 TI - Airway mucosal inflammation. PMID- 1601835 TI - Clinical relevance of lipid mediators in asthma. PMID- 1601837 TI - The effect of immunotherapy on interleukin-1 and tumor necrosis factor production of monocytes in asthmatic children. AB - A longitudinal study was conducted to determine the pathogenesis and effect of immunotherapy (IT) on monocyte function. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes in 31 asthmatic children before and one year after IT was compared. Twenty-two children completed the treatment course, and 13 age-matched healthy children served as controls. Adherent monocytes were isolated and stimulated with either crude mite extract of Dermatophagoid farinae (Df) for 7 days or lipopolysaccharide (LPS) for 3 days. The amount of TNF and IL-1 in culture supernatant was quantified by TNF and IL-1 enzyme-linked immunosorbent assay (ELISA) kits, respectively. The LPS-stimulated TNF production in patients was not different before or after IT (245.8 +/- 110.9 vs. 213.3 +/- 161.6 pg/0.1 ml, p +/- 0.202), but was significantly higher than the control (66.7 +/- 42.7 pg/0.1 ml; p less than 0.0001). The LPS-stimulated IL 1 production was similar among the three groups. When stimulated with Df antigen, monocytes from asthmatic patients produced a greater amount of TNF and IL-1 than did those from the control (p less than 0.001). Furthermore, although the production of TNF decreased after successful IT (360.2 +/- 181.6 vs 243.9 +/- 189.1 pg/0.1 ml, p less than 0.05), the production of IL-1 did not change (679.9 +/- 254.1 vs. 534.8 +/- 257.6 pg/0.1 ml, p greater than 0.05). Thus, repeated long-term administration of allergen (IT) was able to suppress specifically the TNF, but not IL-1 production of monocytes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601836 TI - Asthma: cells and cytokines. AB - The pathology of bronchial asthma demonstrates a multicellular process. In an attempt to elucidate the cellular biology of airways inflammation, it becomes important to understand not only the biology of each individual cell type but also the interaction between different cells. This review focuses on a documentation of some of the biological effects of the constituent cells in the airway mucosa and a discussion of their potential interactions through the release and action of different cytokines. It seems likely that future research will address the in vivo release of different cytokine molecules in the asthmatic process using techniques of molecular biology. There likely will be increasing information available about the regulation and the actions of these molecules on target cells and tissues. Elucidation of some of the complex interactions between different cells and the role of different cytokine molecules may provide a novel approach to the therapy of bronchial asthma. PMID- 1601838 TI - Quality of self-care of patients with asthma. AB - In order to assess the quality of self-care of asthmatic patients in family practice, 150 patients were asked what they did when they felt an attack of asthma coming on. Twenty-four percent said they took no medication. Of the remaining 114 patients, only 49 took appropriate medication. Of these, however, most were not able to demonstrate correct use of their inhaler. This poor quality of self-care may contribute to the undertreatment of asthma in family practice. To improve the quality of care of asthmatic patients, comprehensive treatment is recommended, with the emphasis on improving self-care skills. PMID- 1601839 TI - Three cases of adolescent near-fatal asthma: what do they have in common? AB - Three adolescent asthmatics are described, who suffered from near fatal asthmatic attacks. The events occurred suddenly and required intubation and ventilation. However, the bronchial obstruction was fully reversible within less than 24 hours and the recovery complete. The similarities are discussed and a hypothesis for the differentiation to other well-known severe asthma attacks is introduced. Our three cases might be representative of a certain risk group of asthmatics. PMID- 1601840 TI - Expression and regulation of the human GLUT4/muscle-fat facilitative glucose transporter gene in transgenic mice. AB - To study the molecular basis of tissue-specific expression of the GLUT4/muscle fat facilitative glucose transporter gene, we generated lines of transgenic mice carrying 2.4 kilobases of the 5'-flanking region of the human GLUT4 gene fused to a chloramphenicol acetyltransferase (CAT) reporter gene (hGLUT4[2.4]-CAT). This reporter gene construct was specifically expressed in tissues that normally express GLUT4 mRNA, which include both brown and white adipose tissues as well as cardiac, skeletal, and smooth muscle. In contrast, CAT reporter activity was not detected in brain or liver, two tissues that do not express the GLUT4 gene. In addition, the relative levels of CAT mRNA driven by the human GLUT4 promoter in various tissues of these transgenic animals mirrored those of the endogenous mouse GLUT4 mRNA. Since previous studies have observed alterations in GLUT4 mRNA levels induced by fasting and refeeding (Sivitz, W. I., DeSautel, S. L., Kayano, T., Bell, G. I., and Pessin, J. E. (1989) Nature 340, 72-74), the regulated expression the hGLUT4[2.4]-CAT transgene was also assessed in these animals. Fasting was observed to decrease CAT activity in white adipose tissue which was super-induced upon refeeding. These alterations in CAT expression occurred in parallel to the changes in endogenous mouse GLUT4 mRNA levels. Although CAT expression in skeletal muscle and brown adipose tissue was unaffected, the endogenous mouse GLUT4 mRNA was also refractory to the effects of fasting/refeeding in these tissues. These data demonstrate that 2.4 kilobases of the 5'-flanking region of the human GLUT4 gene contain all the necessary sequence elements to confer tissue-specific expression and at least some of the sequence elements controlling the hormonal/metabolic regulation of this gene. PMID- 1601841 TI - ADP-ribosylation of the ras-related, GTP-binding protein RhoA inhibits lymphocyte mediated cytotoxicity. AB - The Rho proteins are identified as a subgroup of the Ras superfamily of low molecular weight GTP-binding proteins. We have studied the expression of these proteins in human cytotoxic natural killer cells and found that RhoA is the most abundantly expressed member of the Rho family. The Rho proteins are specific substrates for ADP-ribosylation catalyzed by the C3 exoenzyme from Clostridium botulinum. We report here that introduction of recombinant C3 in electropermeabilized natural killer cells or in cytotoxic T lymphocytes resulted in a dose-dependent inhibition of their cytolytic function. Furthermore, a single substrate is efficiently ADP-ribosylated by C3 in extracts from cytotoxic cells. Biochemical analyses indicate that this substrate is RhoA, and subcellular fractionation experiments demonstrate that it is essentially present in the cytosol of the cells. Western blot analysis, however, revealed that a small proportion of the Rho protein can be found associated with the cell membrane as well as with the cytotoxic granules. These results indicate that the low molecular weight GTP-binding protein RhoA is present in cytotoxic lymphocytes and plays a critical role in cell-mediated cytotoxicity. PMID- 1601842 TI - Members of the VAMP family of synaptic vesicle proteins are components of glucose transporter-containing vesicles from rat adipocytes. AB - Existing data support the hypothesis that insulin triggers the exocytosis of small vesicles containing the GluT4 isoform of the glucose transporter. The data also suggest that these vesicles reform through endocytosis of GluT4. These processes resemble those described for synaptic vesicles after depolarization of nerve cells. To determine whether GluT4 vesicles are related to synaptic vesicles, rat adipocyte low density microsomes (LDM), which are rich in GluT4 vesicles, were screened for the synaptic vesicle proteins synaptotagmin, synaptophysin, SV2, p29, rab3, and VAMP (synaptobrevin) by immunoblotting. Two polypeptides that reacted with antibodies against the VAMPs were identified, one with the same apparent size as the two isoforms of VAMP in the brain (18 kDa) and one that was slightly smaller (17 kDa). These members of the VAMP family were highly enriched in GluT4 vesicles isolated by immunoadsorption and translocated from the LDM to the plasma membrane in response to insulin. With the exception of rab3, which was observed in the LDM but was not localized in the GluT4 vesicles, the other synaptic vesicle proteins were not detected. The presence of the VAMPs in both GluT4 and synaptic vesicles suggests that the genesis and/or exocytosis of these two types of vesicles involve shared processes. PMID- 1601843 TI - A specific binding site for K+ channel openers in rat aorta. AB - The K+ channel openers, including cromakalim, pinacidil, minoxidil sulfate, diazoxide, and nicorandil, form a chemically heterogeneous group of compounds, which relax smooth muscle by opening plasmalemmal K+ channels. At present it is not known whether these drugs elicit their effects by binding to the same target, presumably the K+ channel. In order to address this question, a binding assay for K+ channel openers has been developed in vascular smooth muscle. The novel tritiated K+ channel opener, [3H]P1075, an analogue of pinacidil, binds with high affinity (KD = 6 +/- 1 nM) to endothelium-denuded rings of rat aorta. Inhibition studies indicate that the different families of K+ channel openers bind to a common target. Evidence is presented to suggest that the binding site for the sulfonylurea, glibenclamide, the major blocker of the K+ channel openers, is coupled in a negative allosteric manner to the binding site(s) for the openers. The binding assay described here may open the way to the biochemical characterization of the drug receptor for the K+ channel openers. PMID- 1601844 TI - Identification of a conformationally distinct form of plasminogen activator inhibitor-1, acting as a noninhibitory substrate for tissue-type plasminogen activator. AB - Plasminogen activator inhibitor-1 (PAI-1), the primary physiological inhibitor of tissue-type plasminogen activator (t-PA) in plasma, is a serine proteinase inhibitor (serpin) that forms a 1:1 stoichiometric complex with its target proteinase leading to the formation of a stable inactive complex. The active, inhibitory form of PAI-1 spontaneously converts to a latent form that can be reactivated by protein denaturants. In the present study we have isolated another molecular form of intact PAI-1 that, in contrast with active PAI-1, does not form stable complexes with t-PA but is cleaved at the P1-P1' bond (Arg346-Met347). Other serine proteinases, e.g. urokinase-type plasminogen activator and thrombin, also cleaved this "substrate" form of PAI-1. Fluorescence spectroscopy revealed conformational differences between the latent, active, and substrate forms of PAI 1. This observation confirms our hypothesis that the three functionally different forms of PAI-1 are the consequence of conformational transitions. Thus PAI-1 may occur in three interconvertible conformations: latent, inhibitor, and substrate PAI-1. The identification of two distinct conformations of PAI-1 which interact with their target protease either as an inhibitor or as a substrate is a previously unrecognized phenomenon among the serpins. Conversion of substrate PAI 1 to its inactive degradation product may constitute a pathway for the physiological regulation of PAI-1 activity. PMID- 1601845 TI - The high affinity calcium-binding site involved in protein C activation is outside the first epidermal growth factor homology domain. AB - Binding Ca2+ to a high affinity site in protein C and 4-carboxyglutamic acid (Gla)-domainless protein C results in a conformational change that is required for activation by the thrombin-thrombomodulin complex, the natural activator of protein C. It has been hypothesized that this high affinity Ca(2+)-binding site is located in the NH2-terminal epidermal growth factor (EGF) homology region of protein C. We have expressed in human 293 cells a deletion mutant of protein C (E2-PD) which lacks the entire Gla region as well as the NH2-terminal EGF homology region of protein C. Ca2+ inhibits activation of E2-PD or Gla-domainless protein C by thrombin with half-maximal inhibition occurring at Ca2+ concentrations of 103 +/- 11 and 70 +/- 7 microM, respectively, but is required for both E2-PD and Gla-domainless protein C activation by the thrombin thrombomodulin complex with half-maximal acceleration occurring at Ca2+ concentrations of 87 +/- 8 and 89 +/- 8 microM, respectively. Both E2-PD and Gla domainless protein C exhibit a reversible, Ca(2+)- but not Mg(2+)-dependent decrease (6 +/- 1%) in fluorescence emission intensity with Kd = 38 +/- 3 microM Ca2+. We conclude that the high affinity Ca(2+)-binding site important for the activation of protein C is located outside of the NH2-terminal EGF homology region and that the metal-binding site in the NH2-terminal EGF homology region may not be a high affinity site in intact protein C. PMID- 1601846 TI - Squalestatin 1, a potent inhibitor of squalene synthase, which lowers serum cholesterol in vivo. AB - Squalestatin 1 is a member of a novel family of fermentation products isolated from a previously unknown Phoma species (Coelomycetes). Squalestatin 1 is a potent, selective inhibitor of squalene synthase, a key enzyme in cholesterol biosynthesis; in vitro, 50% inhibition of enzyme activity is observed at a concentration of 12 +/- 5 nM (range of 4-22 nM). Squalestatin 1 inhibits cholesterol biosynthesis from [14C]acetate by isolated rat hepatocytes (50% inhibition at 39 nM) and by rat liver in vivo. In marmosets, a species with a lipoprotein profile similar to that of man, squalestatin 1 lowers serum cholesterol by up to 75%. This compound will allow further investigation of the control of the sterol biosynthesis pathway and could also lead to the development of new therapies for elevated serum cholesterol. PMID- 1601847 TI - An essential histidine residue for the activity of UDPglucose 4-epimerase from Kluyveromyces fragilis. AB - UDPglucose 4-epimerase from Kluyveromyces fragilis was completely inactivated by diethylpyrocarbonate following pseudo-first order reaction kinetics. The pH profile of diethylpyrocarbonate inhibition and reversal of inhibition by hydroxylamine suggested specific modification of histidyl residues. Statistical analysis of the residual enzyme activity and the extent of modification indicated modification of 1 essential histidine residue to be responsible for loss in catalytic activity of yeast epimerase. No major structural change in the quarternary structure was observed in the modified enzyme as shown by the identical elution pattern on a calibrated Sephacryl 200 column and association of coenzyme NAD to the apoenzyme. Failure of the substrates to afford any protection against diethylpyrocarbonate inactivation indicated the absence of the essential histidyl residue at the substrate binding region of the active site. Unlike the case of native enzyme, sodium borohydride failed to reduce the pyridine moiety of the coenzyme in the diethylpyrocarbonate-modified enzyme. This indicated the presence of the essential histidyl residue in close proximity to the coenzyme binding region of the active site. The abolition of energy transfer phenomenon between the tryptophan and coenzyme fluorophore on complete inactivation by diethylpyrocarbonate without any loss of protein or coenzyme fluorescence are also added evidences in this direction. PMID- 1601848 TI - Distinct functional roles of two active site thiols in UDPglucose 4-epimerase from Kluyveromyces fragilis. AB - UDPglucose 4-epimerase from Kluyveromyces fragilis was earlier shown to have two conformationally vicinal thiols at the active site. Upon treatment with diamide, these thiols form a disulfide linkage across the subunits that results in coordinated loss of catalytic activity and coenzyme fluorescence (Ray, M., and Bhaduri, A. (1980) J. Biol. Chem. 255, 10777-10786). Employing a number of thiol specific reagents, we now suggest discriminatory and nonidentical roles for these two thiols. Kinetic and statistical analysis of 5,5'-dithiobis-(2-nitrobenzoic acid) and N-ethylmaleimide modification reaction of epimerase show that only one thiol is essential for activity. Consecutive modification experiments clearly show that the same active thiol is modified in both cases. However, significant differences are observed when the reactivity of these reagents is monitored in terms of coenzyme fluorescence. Treatment with N-ethylmaleimide leads to a form of inactive enzyme that fully retains its fluorescent properties whereas modification with 5,5'-dithiobis-(2-nitrobenzoic acid), on the other hand, results in the loss of both activity and fluorescence. The closely spaced nonessential second thiol, which is not modified by N-ethylmaleimide is therefore involved in generating and maintaining the coenzyme fluorescence. Modification studies with a series of spin-labeled maleimide shows that only 3 (maleimidomethyl)proxyl causes partial quenching of coenzyme fluorescence. This suggests that the active thiol is situated at a distance of 4.5 A approximately from the coenzyme fluorophore. PMID- 1601849 TI - A highly specific D-hydroxyisovalerate dehydrogenase from the enniatin producer Fusarium sambucinum. AB - A highly specific D-hydroxyisovalerate (D-HIV) dehydrogenase, which is a key enzyme in depsipeptide synthesis, was purified to near homogeneity from the enniatin-producing fungus Fusarium sambucinum. The enzyme catalyzes the reversible reaction of 2-ketoisovalerate (2-KIV) to D-HIV. It is strictly dependent on NADPH and exhibits a high substrate specificity with respect to 2 KIV. NADH was not accepted by the enzyme. Km values for 2-KIV and NADPH were found to be 200 and 333 microM, respectively. D-HIV dehydrogenase consists of a single polypeptide chain with a molecular mass of about 53 kDa. Optimum temperature for the reduction of 2-KIV was 35 degrees C and for the oxidation reaction was 45 degrees C. The optimum pH was found to be 7 for the reduction and 8-9 for the oxidation reaction. PMID- 1601850 TI - Reversible cryoactivation of recombinant human prorenin. AB - Cleavage of prorenin's prosegment causes irreversible formation of renin. In contrast, renin activity is reversibly exposed when prorenin is acidified to pH 3.3. Nonetheless, acidification of plasma results in irreversible activation of prorenin, because endogenous proteases cleave the prosegment of acid-activated prorenin. Chilling of plasma results in irreversible cryoactivation of prorenin. In this study we investigated whether cryoactivation of purified prorenin is reversible. The intrinsic renin activity of recombinant human prorenin was measured by an enzyme kinetic assay using partially purified human angiotensinogen as substrate. Results are expressed as a percent (mean +/- S.E.) of the maximal activity exposed after limited proteolysis by trypsin. The intrinsic renin activity of two pools (0.3 and 0.06 Goldblatt units/ml) was 1.5% +/- 0.3 and 1.2% +/- 0.6 at 37 degrees C. Activity increased to 19% +/- 0.3 and 26% +/- 0.5 after incubation at 0 degrees C and to 5.4% +/- 0.5 and 2.1% +/- 1.2 at room temperature. Cryoactivation did not occur in buffers containing more than 1 M NaCl. It took 8 min at 37 degrees C or 180 min at room temperature for cryoactivated prorenin to lose half of its intrinsic renin activity. It took 48 and 26 h, respectively, at 0 degree C for the two pools of prorenin at 37 degrees C to regain half of their maximum intrinsic activity at 0 degrees C. A direct immunoradiometric assay that detects active renin but not prorenin was able to detect cryoactivated prorenin. These results show that human prorenin can be reversibly cryoactivated in buffers of low ionic strength and has greater intrinsic activity at room temperature than at 37 degrees C. PMID- 1601851 TI - Polyglycosylceramides with branched N-acetyllactosamine sequences are synthesized by the human pancreatic carcinoma cell line PANC-1. AB - We have metabolically labeled the human pancreatic tumor cell line PANC-1 with high specific activity tritiated sugar precursors to study the expression of glycosphingolipids by this cell type. We have used a combination of detergent solubilization, exhaustive protease digestion, ceramide glycanase digestion, and reverse-phase chromatography to isolate glycosphingolipid-derived oligosaccharides specifically labeled in their component sugars. A significant proportion of the oligosaccharides derived from polar glycosphingolipids were of high molecular mass (greater than 2000 Da). The results of compositional studies, lectin affinity chromatography, and methylation analysis suggested that this high molecular weight fraction consists of lactosaminoglycan type oligosaccharides derived from polyglycosylceramides. There are on average three beta 1-6 linked N acetyllactosamine branches attached to the polylactosamine backbone in this type of glycosphingolipid-derived oligosaccharide. The majority of the oligosaccharides also contain 1-2 mol of sialic acid that are linked alpha 2-3 to penultimate galactose. The results indicate that PANC-1 cells, like human colorectal tumor cells, express highly extended neolacto type glycosphingolipids. However, the lactosaminoglycan sequences are highly branched, unlike those associated with colorectal tumor cells. PMID- 1601852 TI - Quantitation of rat tissue thyroid hormone binding receptor isoforms by immunoprecipitation of nuclear triiodothyronine binding capacity. AB - A panel of anti-thyroid hormone receptor (TR) antisera were generated to allow direct assay of the concentrations of the alpha 1 and beta 1 receptor isoforms in nuclear extracts from adult rat liver, kidney, brain and heart, and fetal brain. An antiserum, immunoglobulin G (IgG)-beta 1, raised against amino acid sequence 62-92 of the rat TR-beta 1 specifically precipitated only TR-beta 1 in vitro translation products. A second antiserum, IgG-alpha 1/beta, generated against a sequence that is identical in the ligand binding region of rat TR-alpha 1 and TR beta isoforms immunoprecipitated both TR-alpha 1 and -beta 1 translation products. These IgG preparations were used to specifically immunoprecipitate thyroid hormone receptor binding activity from nuclear extracts. IgG-beta 1 cleared almost 80%, and the IgG-alpha 1/beta immunoprecipitated nearly all binding from hepatic nuclear extracts. This distribution of TR protein, 80% beta 1 and 20% alpha 1, is the same as previously reported for their respective mRNAs in liver. In heart, kidney, and brain IgG-beta 1 cleared 45, 43, and 28% of total binding, respectively, and IgG-alpha 1/beta cleared all T3 binding activity from these tissues. In agreement with an earlier study, marked variations in specific protein/mRNA ratios were noted among these tissues. Consistent with our earlier report of the presence of only very low levels of TR-beta 1 mRNA in fetal brain, IgG-beta 1 cleared just 5% of binding in this tissue. Studies using an antiserum (IgG-ch) generated against homologous segments of the hinge region in both TR alpha 1 and -beta 1 yielded results which contrasted sharply with those of IgG alpha 1/beta. Whereas IgG-ch could also immunoprecipitate virtually all binding from hepatic extracts it cleared only 40-50% of binding from the other tissues, including fetal brain in which TR-alpha 1 accounts for greater than 90% of binding protein. The data suggest the presence of posttranslational modification of the TR-alpha 1 protein in the hinge region, consistent with the presence in this segment of potential phosphorylation sites. PMID- 1601853 TI - Human meconium gangliosides. Characterization of a novel I-type ganglioside with the NeuAc alpha 2-6Gal structure. AB - Three monosialogangliosides containing the NeuAc alpha 2-6Gal structure have been detected in human meconium by immunological analysis using a monoclonal antibody, MSG-15, and purified by repeated silica beads column chromatography. One was previously shown to be NeuAc alpha 2-6Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc beta 1-1Cer. The remaining two were characterized by proton NMR, fast atom bombardment mass spectrometry, methylation analysis by gas chromatography-mass spectrometry, and immunological studies, and their structures were concluded to be as follows. [formula: see text] The second ganglioside has the same structure that was isolated from bovine buttermilk (Takamizawa, K., Iwamori, M., Mutai, M., and Nagai, Y. (1986) J. Biol. Chem. 261, 5625-5630), and this is the first description of the occurrence of the ganglioside with the branched structure with two N-acetyllactosamines linked to lactosylceramide via beta 1-6 and beta 1-3 in human linked to lactosylceramide via beta 1-6 and beta 1-3 in human tissues. The third ganglioside is a novel ganglioside with blood group I-type and a NeuAc alpha 2-6Gal structure. PMID- 1601854 TI - Truncated phenylalanine ammonia-lyase expression in tomato (Lycopersicon esculentum). AB - Southern blot analyses of genomic DNA fragments suggest there are five different classes of phenylalanine ammonia-lyase (PAL, EC 4.3.1.5) genomic sequence in tomato (Lycopersicon esculentum). Isolation and subsequent sequence analysis of three examples from genomic libraries reveal highly homologous coding sequences but also a surprisingly high frequency of single point mutations which would truncate protein synthesis. The nucleotide sequence for one of the genes (PAL5) encodes a normal polypeptide of 721 amino acids, interrupted by a 710-base pair intron in the codon for amino acid 139. In contrast, premature stop codons, 363 triplets from the end in PAL1 and 304 triplets from the end in PAL3 would result in substantially (51-43%) shorter polypeptides that are consistent with the protein polymorphism, recently reported in alfalfa (Jorrin, J., and Dixon, R. A. (1990) Plant Physiol. 92, 447-445) but ascribed to protein degradation. S1 mapping of the mRNA termini and polymerase chain reaction analysis of cDNA transcripts indicate that at least one of these truncated coding sequences is expressed, strongly suggesting that at least some of the shorter polypeptides constitute original gene products with a potentially important function. PMID- 1601855 TI - Regulation of the Ca2+ dependence of smooth muscle contraction. AB - Cellular mechanisms for the regulation of Ca(2+)-dependent myosin light chain phosphorylation were investigated in bovine tracheal smooth muscle. Increases in the free intracellular Ca2+ concentration ([Ca2+]i), light chain phosphorylation, and force were proportional to carbachol concentration. KCaM, the concentration of Ca2+/calmodulin required for half-maximal activation of myosin light chain kinase, also increased proportionally, presumably due to Ca(2+)-dependent phosphorylation of the kinase. Isoproterenol treatment inhibited agonist-induced contraction by decreasing [Ca2+]i and thereby light chain phosphorylation. Depolarization by increasing concentrations of KCl also resulted in proportional increases in [Ca2+]i, KCaM, light chain phosphorylation, and force. However, the [Ca2+]i required to obtain a given value of either light chain phosphorylation or KCaM was greater in KCl-depolarized tissues compared to carbachol-treated tissues. In muscles contracted with KCl, isoproterenol treatment resulted in diminished light chain phosphorylation and force without alterations in [Ca2+]i or KCaM. Thus, isoproterenol inhibition of KCl-induced contraction results from a cellular mechanism different from that found in agonist-induced contraction. In neither case does isoproterenol produce relaxation by altering the calmodulin activation properties of myosin light chain kinase. PMID- 1601856 TI - Mapping Z-DNA in the human genome. Computer-aided mapping reveals a nonrandom distribution of potential Z-DNA-forming sequences in human genes. AB - In this work, we have predicted and mapped the potential Z-DNA-forming sequences in over one million base pairs of human DNA, containing 137 complete genes. The computer program (Z-Hunt-II) developed for this study uses a rigorous thermodynamic search strategy to map the occurrence of left-handed Z-DNA in genomic sequences. The search algorithm has been optimized to search large sequences for the potential occurrence of Z-DNA, taking into account sequence type, length, and cooperativity for a given stretch of potential Z-DNA-forming nucleotides. In this extensive data set we have identified 329 potential Z-DNA forming sequences. The exact locations of the potential Z-DNA-forming sequences in the data set have been mapped with respect to the location of structural features of the genes. This analysis reveals a distinctly nonrandom distribution of potential Z-DNA-forming sequences across human genes and, most notably, that strong Z-DNA-forming sequences are more commonly found near the 5' ends of genes. We find that 35% of the Z-DNA-forming sequences are located upstream of the first expressed exon, while only 3% of the sequences are located downstream of the last expressed exon. The remaining 62% of the Z-DNA-forming sequences, which are located either in introns (47.1%) or exons (14.9%), are also nonrandomly distributed, with a strong bias toward locations near the site of transcription initiation. We interpret this distribution of potential Z-DNA-forming sequences toward the 5' end of human genes in terms of the well established "twin-domain model" of transcription-induced supercoiling and the effect of this topological strain on Z-DNA formation in eukaryotic cells. PMID- 1601857 TI - The primary structure of the flavoprotein D-aspartate oxidase from beef kidney. AB - The complete primary structure of the peroxisomal flavoenzyme D-aspartate oxidase from beef kidney has been determined by analyses of the peptides obtained through fragmentation of the carboxymethylated protein with trypsin, CNBr, heptafluorobutyric acid/CNBr and Staphylococcus aureus V8 protease. The protein consists of a single polypeptide of 338 residues, accounting for a M(r) of 37,305 for the apoprotein. A form of the enzyme lacking Lys-338 and therefore ending with Pro-337 has been detected. The N-terminal residue is blocked. Seven cysteines and no disulfide bridges are present. Residue 228 can be either Ile or Val. Thus, D-aspartate oxidase presents two types of heterogeneity in the polypeptide chain in addition to the one already described concerning the possible content of FAD or 6-hydroxyflavin adenine dinucleotide. Comparison of the primary structure of D-aspartate oxidase with other known sequences reveals that D-aspartate oxidase is homologous with D-amino acid oxidase (another flavo oxidase) and does not present significant sequence similarities with any other protein, including flavoenzymes. PMID- 1601858 TI - Regio- and enantioselectivity of soybean fatty acid epoxide hydrolase. AB - Soluble epoxide hydrolase purified from soybean catalyzes trans-addition of water across the oxirane ring of cis-9,10-epoxystearic acid with inversion of configuration at the attacked carbon, yielding threo-9,10-dihydroxystearic acid. Kinetic analyses of the progress curves, obtained at low substrate concentrations (i.e. [S] much less than Km), and determination of the enantiomeric excess of the residual substrate by chiral-phase high-performance liquid chromatography at different reaction times, indicate that the epoxide hydrolase hydrates preferentially cis-9R, 10S-epoxystearic acid (V/Km ratio, approximately 20). Interestingly, this enantiomer is obtained by epoxidation of oleic acid catalyzed by peroxygenase, a hydroperoxide-dependent oxidase, we have previously described in soybean (Blee, E., and Schuber, F. (1990) J.Biol. Chem. 265, 12887-12894). For the epoxide hydrolase to show high enantioselectivity there must be a free carboxylic acid functionality on the substrate which probably influences its positioning within the active site. This selectivity, which in principle can be used for kinetic resolution of the cis-9,10-epoxystearic acid enantiomers, is much reduced with methyl cis-9,10-epoxystearate. 18O-Labeling experiments indicate that water attacks both cis-9,10-epoxystearic acid enantiomers on the oxirane carbon which has the S-chirality. Results show that soybean epoxide hydrolase produces exclusively threo-9R,10R-dihydroxystearic acid, i.e. a naturally occurring metabolite in higher plants. cis-9,10-Epoxy-18-hydroxystearic acid, a cutin monomer, was a poorer substrate of the epoxide hydrolase than 9,10 epoxystearic acid (V/Km ratio for the preferred enantiomers, approximately 19). From a physiological point of view, peroxygenase and this newly described epoxide hydrolase could be responsible, in vivo, for the biosynthesis of a class of oxygenated fatty acid compounds known to be involved in cutin monomers production and in plant defense mechanisms. PMID- 1601859 TI - An insight into domain structures and thermal stability of gamma-crystallins. AB - The thermal behavior of gamma II, gamma IIIA, gamma IIIB, and gamma IVA crystallin, from calorimetric and spectral studies, has been analyzed in terms of selective unfolding of domains, interdomain interactions, conformational stability, and the existence of intermediates in the order-disorder transition equilibrium. The major endothermic transition (Tm) observed calorimetrically for all four fractions occurs between 67 and 78 degrees C, with enthalpy change (delta H) from 80 to 150 kcal/mol, values that agree reasonably well with those from spectroscopic measurements. gamma II and gamma IIIB show a second thermal event at T less than Tm whereas gamma IIIA and gamma IVA showed no additional transition. Urea-induced equilibrium unfolding of gamma II at acidic pH, unlike gamma IVA, is biphasic as monitored by CD and fluorescence, indicating the existence of an intermediate. The absence of a cooperative transition in gamma IVA in acidic urea and the appearance of a single endotherm in differential scanning calorimetry at low pH have been attributed to a structured intermediate that melts at low temperature. The difference in the folding/unfolding of gamma II and gamma IVA has been explained by subtle differences in the packing arrangement of their two domains and interactions between them. Thermal aggregation of gamma-crystallins could be prevented either by preincubation with ionic detergents or at low pH or in the presence of chemical denaturant, indicating that the protein surface charge and solvent polarity influence their stability. An increase in the 8-anilino-1-naphthalenesulfonate-bound fluorescence during heat denaturation also suggests that the thermal aggregation is governed by hydrophobic interactions. PMID- 1601860 TI - Peroxides of vanadate induce activation of phospholipase D in HL-60 cells. Role of tyrosine phosphorylation. AB - To determine the role of protein tyrosine phosphorylation in the activation of phospholipase D (PLD), electropermeabilized HL-60 cells labeled in [3H]alkyl phosphatidylcholine were treated with vanadate derivatives. Micromolar concentrations of vanadyl hydroperoxide (V(4+)-OOH) induced accumulation of tyrosine-phosphorylated proteins. Concomitantly, V(4+)-OOH or a combination of vanadate and NADPH elicited a concentration- and time-dependent accumulation of phosphatidic acid (PtdOH). In the presence of ethanol a sustained formation of phosphatidylethanol was observed, indicating that a type D phospholipase was activated. A good correlation was found to exist between the accumulation of tyrosine-phosphorylated proteins and activation of PLD. The V(4+)-OOH concentration dependence of the two responses was nearly identical, and the time course of activation was similar, with tyrosine phosphorylation preceding PLD activation by approximately 1 min. The ability of V(4+)-OOH to induce both responses was found to be strictly dependent on the presence of ATP and/or Mg2+, suggesting that PLD activation involves phosphotransferase reactions. Accordingly, ST638, a tyrosine kinase inhibitor, reduced concomitantly tyrosine phosphorylation and PLD activation elicited by V(4+)-OOH. The mechanism of action of V(4+)-OOH was investigated. The diacylglycerol kinase inhibitors, dioctanoylethylene glycol and R59022 potentiated PLD stimulation by exogenous diacylglycerol but not by V(4+)-OOH. Moreover, stimulation by V(4+)-OOH and by phorbol esters was synergystic. Therefore, diacylglycerol-induced activation of protein kinase C is unlikely to mediate the effects of V(4+)-OOH. The response of PLD to V(4+)-OOH was larger than that to guanosine 5'-(gamma-thio)triphosphate. Moreover, the effects of GTP gamma S and V(4+)-OOH were additive. Hence, activation of G proteins cannot account for the stimulation of PLD by V(4+)-OOH. V(4+)-OOH also triggers a burst of O2 consumption by the NADPH oxidase. Inhibition of PtdOH accumulation by addition of ethanol or by ST638 abolished this respiratory burst. Together, the results establish a strong correlation between tyrosine phosphorylation, PLD activation, and stimulation of the NADPH oxidase in HL-60 cells, suggesting a causal relationship. PMID- 1601861 TI - Cell surface and intracellular functions for ricin galactose binding. AB - The role of the two galactose binding sites of ricin B chain in ricin toxicity was evaluated by studying a series of ricin point mutants. Wild-type (WT) ricin and three ricin B chain point mutants having mutations in either 1) the first galactose binding domain (site 1 mutant, Met in place of Lys-40 and Gly in place of Asn-46), 2) the second galactose binding domain (site 2 mutant, Gly in place of Asn-255), or 3) both galactose binding domains (double site mutant containing all three amino acid replacements formerly stated) were expressed in Xenopus oocytes and then reassociated with recombinant ricin A chain. The different ricin B chains were mannosylated to the same extent. Cytotoxicity of these toxins was evaluated when cell entry was mediated either by galactose-containing receptors or through an alternate receptor, the mannose receptor of macrophages. WT ricin and each of the single domain mutants was able to kill Vero cells following uptake by galactose containing receptors. Lactose blocked the toxicity of each of these ricins. Site 1 and 2 mutants were 20-40 times less potent than WT ricin, and the double site mutant had no detectable cytotoxicity. WT ricin, the site 1 mutant, and the site 2 mutant also inhibited protein synthesis of mannose receptor-containing cells. Ricin can enter these cells through either a cell surface galactose-containing receptor or through the mannose receptor. By including lactose in the cell medium, galactose-containing receptor-mediated uptake is blocked and cytotoxicity occurs solely via the mannose receptor. WT ricin, site 1, and site 2 mutants were cytotoxic to macrophages in the presence of lactose with the relative potency, WT greater than site 2 mutant greater than site 1 mutant. The double site mutant lacked cytotoxicity either in the absence or presence of lactose. Thus, even for mannose receptor-mediated toxicity of ricin, at least one galactose binding site remains necessary for cytotoxicity and two galactose binding sites further increases potency. These results are consistent with the model that the ricin B chain galactose binding activity plays a role not only in cell surface binding but also intracellularly for ricin cytotoxicity. PMID- 1601862 TI - Identification of cell-surface heparin/heparan sulfate-binding proteins of a human uterine epithelial cell line (RL95). AB - The interaction of heparin (HP) with the cell-surface components of a human uterine epithelial carcinoma cell line (RL95) was studied. Binding of [3H]HP to cell surfaces was saturable in a dose- and time-dependent manner. HP and certain forms of heparan sulfate (HS) efficiently compete for [3H]HP binding. In contrast, other glycosaminoglycans, such as chondroitin sulfate, keratan sulfate, hyaluronic acid, and dermatan sulfate, do not compete for binding to these sites. Scatchard analysis revealed that [3H]HP bound to these sites with an apparent KD of 0.7-0.9 microM and a binding capacity of 9 x 10(6) sites/cell to attached cells. EDTA-detached cells displayed a similar apparent KD, but an approximately 2-fold increase in binding capacity. Protease digestion of cells on ice markedly reduced [3H]HP binding, indicating that these binding sites were associated with proteins. In contrast, heparinase treatment of cells stimulated binding by approximately 2-fold, indicating that a large fraction of these binding sites were occupied with endogenous ligand. We examined the structural features of HP/HS required for HP/HS binding. O-Sulfation, substitution of amino groups, and, to a lesser extent, the presence of carboxyl groups were important recognition features of HP/HS by cell-surface HP/HS-binding sites. N-Sulfation was not required. Photoaffinity labeling with 125I-sulfosuccinimidyl 2-(p azidosalicylamido)-ethyl-1, 3-dithiopropionate-HP was used to identify HP/HS binding proteins on RL95 cell surfaces. Proteins with M(r) values of 14,000 18,500 and 31,000 were photolabeled at the surfaces of attached cells. Photolabeling was blocked by the addition of excess HP, but not chondroitin sulfate. Additional proteins with M(r) values greater than 31,000 were photolabeled specifically on EDTA-detached cells. Moreover, the M(r) 14,000 18,500 and 31,000 proteins were retained on the EDTA-detached cells. These observations indicated that certain cell-surface HP/HS-binding proteins were not exposed when cells were attached to substrata. Proteins of similar M(r) values as the photolabeled components as well as many additional proteins were identified by heparin-agarose chromatographic selection of extracts of cells labeled metabolically with [35S]methionine or vectorially with Na125I at the cell surface. Fragments of cell-surface HP/HS-binding proteins were released from intact RL95 and mouse uterine epithelial cells by mild trypsinization and isolated by heparin-agarose affinity chromatography. Three peptides with M(r) values between 6000 and 14,000 required greater than 0.5 M salt for elution from heparin-agarose, retained HP binding activity in a 125I-HP gel overlay assay, and selectively bound [3H]HP in a solid-phase binding assay.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1601863 TI - Enzymatic deglycosylation of human Band 3, the anion transport protein of the erythrocyte membrane. Effect on protein structure and transport properties. AB - The structural and functional roles of the single asparagine (N)-linked oligosaccharide chain of Band 3 (AE1), the anion transport protein of the human erythrocyte membrane, were examined. Purified Band 3 (M(r) = 95,000) in 0.1% octaethylene glycol mono n-dodecyl ether (C12E8) detergent solution was deglycosylated using N-glycosidase F. This treatment sharpened the protein band on sodium dodecyl sulfate gel electrophoresis and decreased its apparent molecular weight by 5,000. The purified membrane domain could be deglycosylated under similar conditions, causing a shift from a broad band centered at 55 kDa to a sharp 46-kDa band. Band 3 was shown to bind tomato lectin, and loss of lectin binding on blots provided a sensitive assay for deglycosylation. Carbohydrate analysis revealed that greater than 80% of the oligosaccharide could be removed from Band 3 by N-glycosidase F digestion. The deglycosylated protein maintained its dimeric structure and level of detergent binding but had a smaller Stokes radius (RS = 72 A) than native Band 3 (RS = 75 A). The Stokes radius of the membrane domain (RS = 60 A) also decreased upon deglycosylation (RS = 58 A). Circular dichroism studies showed that deglycosylation did not change the secondary structure of Band 3 or the membrane domain. The sensitivity of Band 3 or the membrane domain to proteolytic digestion by trypsin or proteinase K was also unaffected by deglycosylation. The deglycosylated protein aggregated more rapidly and was much more readily precipitable by ammonium sulfate. The deglycosylated protein bound the anion transport inhibitor 4-benzamido-4'-amino stilbene-2,2'-disulfonate with the same affinity (Kd = 1 microM) as the native protein. Transport studies using reconstituted Band 3 and resealed ghosts showed that deglycosylated Band 3 retained its ability to transport anions. We conclude that removal of the oligosaccharide chain from Band 3 and any resultant structural changes had no effect on the transport function of this protein. PMID- 1601864 TI - A receptor binding domain of mouse interleukin-4 defined by a solid-phase binding assay and in vitro mutagenesis. AB - Interleukin 4 (IL-4) is a potent, pleiotropic lymphokine that affects a variety of cells, especially those of hematopoietic origin. Although murine and human IL 4 are homologous proteins, they display a species specificity in which murine IL 4 acts only upon mouse cells, and human IL-4 only upon human cells. We have used a mutagenesis strategy to define both the structural determinants of this specificity and a receptor binding domain of murine IL-4. To do this, we developed convenient solid-phase binding assays for mouse and for human IL-4, each utilizing receptor-immunoglobulin fusion proteins and alkaline phosphatase tagged ligands. These were employed to assess the receptor binding activities of wild type and mutant forms of IL-4. In a separate biological assay, we measured the ability of each version of IL-4 to induce proliferation of a cultured mouse T cell line. By replacing regions of mouse IL-4 with homologous segments of human IL-4, we found that the amino-terminal 16 residues and the carboxyl-terminal 20 residues of murine IL-4 are required for species-specific receptor binding as well as for T-cell proliferation. A major portion of the amino acid sequence between these regions can be substituted between mouse and human without loss of receptor binding or biological activity. Further, alanine-scanning mutagenesis revealed specific residues in the amino- and carboxyl-terminal regions (Glu-12, Ile-14, Leu-104, Asp-106, Phe-107, and Leu-111) that bear side chains critical for function. An analysis of the carboxyl-terminal region of murine IL-4 and its comparison with carboxyl-terminal regions of other related cytokines suggest an evolutionary conservation of structural and functional features. PMID- 1601865 TI - The presence of uracil-DNA glycosylase in insects is dependent upon developmental complexity. AB - The metamorphosis of insects can, in a general way, be divided between those organisms that undergo pupation accompanied by cellular histolysis and those that gradually develop into adults without an intervening pupal stage of development. In the former case, the death of a cell population is an integral part of development that is tightly associated with massive DNA degradation during pupation. In that regard, it has been suggested that uracil-containing DNA acts as a target for the nucleolytic breakdown of DNA during histolysis in insects (Deutsch, W. A. (1987) Mutat. Res. 184, 209-215), thus placing into question how compatible the existence of uracil-DNA glycosylases would be for this form of developmental signal. As a result, we tested for the presence of a uracil-DNA glycosylase in insects representative of those having an intervening pupal stage of development and those that do not. We show here that a nonpupating insect contains a uracil-DNA glycosylase activity. Conversely, crude extracts of Drosophila melanogaster, as well as of three other insect populations that undergo pupation similar to that found in Drosophila, do not contain detectable levels of this DNA repair activity. Thus, there appears to be a consistent correlation between cellular destruction during development and the absence of a uracil-DNA glycosylase, which supports the possibility that uracil-containing DNA may play an important role in those cells targeted for death. PMID- 1601866 TI - Leukocyte chemotactic activity of cyclophilin. AB - During the purification of eosinophil chemotactic factors synthesized by the uterus in response to estrogen we isolated a protein having an N-terminal (15 amino acids) sequence identical to that of rat cyclophilin. Our data demonstrate that cyclophilin, a cytosolic protein isolated from bovine thymocytes, which specifically binds the immunosuppressive drug cyclosporin A, as well as recombinant human cyclophilin, displays eosinophil chemotactic activity. In addition to its chemotactic activity, cyclophilin stimulated the release of peroxidase activity from eosinophils. Maximal chemotactic activity of cyclophilin was achieved at a concentration of approximately 10 nM. At similar concentrations cyclophilin was also able to stimulate the migration of neutrophils. This chemotactic activity could be prevented by the addition of cyclosporin A, but not by a nonimmunosuppressive analog (1-fur-furyl-cyclosporin A) at similar concentrations. This chemotactic activity may represent an additional mechanism by which immunosuppressive drugs function to prevent tissue rejection. PMID- 1601867 TI - Hyperprocessing of tRNA by the catalytic RNA of RNase P. Cleavage of a natural tRNA within the mature tRNA sequence and evidence for an altered conformation of the substrate tRNA. AB - In the transposon copia-related retrovirus-like particles of Drosophila, a 39 nucleotide-long fragment from the 5'-region of Drosophila initiator methionine tRNA (tRNA(iMet)) is used as the primer for copia minus-strand reverse transcription. This primer tRNA(iMet) fragment is thought to be produced by cleavage within the mature tRNA(iMet) sequence. We call this cleavage hyperprocessing. We have previously reported that catalytic RNA of RNase P from Escherichia coli (M1RNA) cleaves the synthetic tRNA(iMet) precursor in vitro at several sites within the mature tRNA sequence. Based on this result, we proposed a model for formation of the primer tRNA fragment involving RNase P. Here we show that natural tRNA(iMet) prepared from Drosophila adult flies can be cleaved by M1RNA. Using mutant tRNA(iMet) substrates, we also show that these cleavages are dependent on the occurrence of an altered conformation of the tRNA substrate. This is evidence that a tRNA can exist in aqueous solution at least in part in an altered conformation. PMID- 1601868 TI - Ligand binding by the chlorocruorin from Eudistylia vancouverii. AB - Carbon monoxide chlorocruorin from Eudistylia vancouverii shows three distinct first-order relaxations with rates of 2.9 x 10(9) s-1, 6.5 x 10(7) s-1, and 3.2 x 10(6) s-1 (geminate reactions) and three second-order relaxations with rates of 4.7 x 10(6) M-1 s-1, 7 x 10(5) M-1 s-1, and 7 x 10(4) M-1 s-1, when studied by flash photolysis. The amplitudes of the second-order reactions depend on the extent of photolysis. This may be due to relaxation from the liganded (R) to the unliganded (T) conformation following photolysis and suggests that the combination rates contribute to cooperativity. In a stopped-flow experiment only the slowest phase with a rate of 7 x 10(4) M-1 s-1 is observed. It is assigned to binding to the T-state protein. Fragments of the native protein containing 12 and 4 hemes react like the holoprotein suggesting that the tetramer is a major cooperative unit. Oxygen binding shows three geminate relaxations with rates of 2.5 x 10(10) s-1, 3.5 x 10(7) s-1, and 4.5 x 10(6) s-1, and two second-order rates of 1.5 x 10(7) M-1 s-1 and 1 x 10(6) M-1 s-1. The amplitudes of the second order phases do not correlate with the extent of photolysis. The results with the two ligands are consistent with an allosteric transition fast enough to compete with a rebinding rate of 500 s-1 in the R to T direction (CO rebinding) but not fast enough to compete with oxygen rebinding. There is significant heterogeneity in the R-state kinetics, but the T-state reaction is homogeneous. PMID- 1601869 TI - Positive and negative cis-acting regulatory elements mediate expression of the mouse vascular smooth muscle alpha-actin gene. AB - Segments of the 5'-flanking region of the mouse vascular smooth muscle alpha actin gene were assayed for promoter activity in transfected mouse BC3H1 myogenic cells and AKR-2B embryonic fibroblasts. The region between -150 and -191 that functions as a positive transcriptional element in myogenic and fibroblastic cells contains a mammalian-specific inverted CC(A/T)6GG-type consensus sequence. Expression was restricted to fully differentiated myogenic cells when an additional sequence spanning -191 to -224 was included in reporter gene constructs. This 33-base pair (bp) negative regulatory element is 70% conserved between the mouse and human genes and contains a 10-bp motif at its 3' end that only partially resembles a CC(A/T)6GG element. Retention of a GGGA motif at the 3' boundary of the 33-bp region is sufficient to maintain full transcriptional repression in fibroblasts and is partly responsible for repression in undifferentiated myoblasts. Complete muscle tissue-restrictive expression requires an additional 8 bp from the CC(A/T)6GG-like element immediately 5' to the GGGA motif, since replacement of this region with an unrelated 10-bp sequence completely eliminated restrictive transcriptional behavior in undifferentiated myoblasts. The distal portion of the 5'-flanking region between -224 and -1074 contains six E-box motifs (CANNTG) and mediates high level transcription only in postconfluent BC3H1 myoblasts. Analysis of reporter gene constructs including either the proximal E-box at -240 or all six E-boxes indicate that the five distal E-boxes are not required for high level transcription. A 724-bp segment of the 5'-flanking region consisting of the proximal E-box flanked upstream by a mammalian-specific 352-bp region was sufficient for maximal transcriptional activation in postconfluent BC3H1 myoblasts. Deletion of the 352-bp region restricts the early transcriptional response to high cell density in temporal studies of promoter activity during BC3H1 myogenic cell differentiation. PMID- 1601870 TI - Splicing of two alternative exon pairs in beta-tropomyosin pre-mRNA is independently controlled during myogenesis. AB - Two known tissue-specific tropomyosin (TM) isoforms are produced from the rodent beta-TM gene. Skeletal muscle beta-TM uses the alternative exons 6b and 9a and the exon 9a-associated poly(A) site. Fibroblast and smooth muscle TM-1 use exons 6a and 9b and the exon-9b associated poly(A) site. We have identified a new skeletal muscle beta-TM isoform, beta-TM2. beta-TM2 contains exon 6b (muscle) and exon 9b (nonmuscle). Full-length beta-TM2 cDNA clones were isolated from a cDNA library of mouse muscle BC3H1 cells. Its mRNA was also found in mouse skeletal muscle tissue but not in other tissues. beta-TM2 mRNA level and protein synthesis are differentiation-dependent, with a transient high level in the early stages of myogenesis both in BC3H1 cells and in mouse embryo limbs. Trace amounts of beta TM3 mRNA, the other hybrid form (exons 6a + 9a), were found in less differentiated BC3H1 cells, mouse uterus, heart, and 3T3 fibroblasts but not skeletal muscle tissue. Thus, the selection of the two alternative exons appears to be controlled independently. Furthermore, during myogenesis, there is a sequential switch in the internal alternative exon, the terminal exon, and the poly(A) site from the nonmuscle to the muscle type. PMID- 1601871 TI - Endogenous glycosphingolipids move to the cell surface at a rate consistent with bulk flow estimates. AB - The bulk flow model of intracellular trafficking predicts that forward transport from the ER through the Golgi to the plasma membrane proceeds by default without a special signal being required (Wieland, F.T., Gleason, M. L., Serafini, T. A., and Rothman, J. E. (1987) Cell 50, 289-300). We tested a crucial prediction of this model, which is that the endogenous lipid components of the transport vesicles would reach the plasma membrane at the rapid rate of bulk flow. The rate at which endogenous glycosphingolipids moved from the ER through the Golgi to the plasma membrane was determined in Chinese hamster ovary cells using metabolic labeling with tritiated palmitate and oxidation of cell surface ganglioside NeuAc alpha 2----3Gal beta 1----4Glc beta 1----4Cer (GM3) with periodate. Whereas radioactive precursor became incorporated into ceramide and glucosyl ceramide without a detectable lag, synthesis of labeled lactosyl ceramide and ganglioside GM3 did not begin until 5-6 min and 11-12 min, respectively, after addition of labeled precursor. Labeled GM3 reached the plasma membrane 5-6 min following its synthesis. Overall, approximately 18 min transpired from the time that the ceramide precursor was synthesized in the ER until labeled GM3 reached the plasma membrane. These results indicate that lipid transport vesicles move rapidly to the plasma membrane at a rate consistent with bulk flow estimates. PMID- 1601872 TI - Biochemical fractionation and characterization of proteins from Golgi-enriched membranes. AB - Fractions enriched in Golgi membranes were prepared from rat liver by sucrose gradient ultracentrifugation. These enriched membranes were further subfractionated on the basis of their solubilities in EGTA, 150 mM sodium carbonate, pH 11.5, sodium deoxycholate, Triton X-100, or sodium dodecyl sulfate. This led to isolation of peripheral, luminal, and integral membrane proteins of the Golgi-enriched membranes. Luminal and membrane proteins were further purified by wheat germ agglutinin and concanavalin A lectin affinity chromatographies. Some proteins from these lectin columns were resolved by preparative gel electrophoresis and microsequenced. Subsequently, antibodies were produced for two proteins by immunization of either mice or rabbits. Immunofluorescence microscopy suggests that these proteins are confined to Golgi apparatus-like structures. The protocol described is well suited for the study of organelle structure and function. PMID- 1601873 TI - Ligand-dependent secretion of rat retinol-binding protein expressed in HeLa cells. AB - A minigene encoding rat retinol-binding protein (RBP) was transfected into HeLa cells, which do not express endogenous RBP, transthyretin, or cellular retinol binding protein. The HeLa cells manufactured and secreted the transfected gene product, demonstrating that RBP-transthyretin assembly is not a requirement for the secretion of RBP. When HeLa cells were grown under vitamin A-deficient conditions, RBP accumulated in the endoplasmic reticulum. Both serum and retinol stimulated secretion of RBP in a concentration-dependent manner. The retinol regulated secretion occurred also after protein synthesis had been blocked by cycloheximide. Addition of holo-RBP or retinal, but not retinoic acid, stimulated secretion of RBP. Thus, an in vitro model system that resembles the rat hepatocyte in vivo with regard to the known regulation of RBP secretion has been established in a human cell line of extrahepatic origin. It can be concluded that cellular retinol-binding protein is not required for the transfer of retinol to RBP and that the mechanism whereby retinol controls the intracellular transport of RBP is neither specific for tissues synthesizing RBP nor species-specific. To investigate the structural properties responsible for the endoplasmic reticulum retention of RBP in the absence of its ligand, a cDNA encoding chicken purpurin, a protein that is 50% identical to RBP and that binds retinol, was expressed in HeLa cells. In contrast to RBP, purpurin was not retained in vitamin A-deficient HeLa cells. PMID- 1601874 TI - Sequence and characterization of Bacillus subtilis CheW. AB - A Bacillus subtilis open reading frame (ORF) encoding a predicted polypeptide of 156 amino acids was subcloned and sequenced. The polypeptide was found to be homologous to CheW of Escherichia coli, sharing 28.6% amino acid identity. The ORF was verified by using a bacteriophage T7 expression system in E. coli. The gene was inactivated by insertion of a nonpolor chloramphenicol acetyltransferase cassette in its N-terminal region. In the absence of chemoeffectors, the mutant displayed a smooth swimming bias, with some tumbling. The CheW- mutant was defective on swarm plates but was complemented by a plasmid that expressed wild type CheW. Addition of attractant or repellent to the CheW- mutant resulted in transient smooth swimming or tumbling, respectively. However, capillary assays revealed that chemotaxis was substantially impaired in the mutant strain. PMID- 1601875 TI - Stable binding of the eukaryotic acidic phosphoproteins to the ribosome is not an absolute requirement for in vivo protein synthesis. AB - The genes encoding the four acidic ribosomal phosphoproteins have been inactivated in Saccharomyces cerevisae by recombination with truncated genes carrying different genetic markers. By crossing single haploid disruptants, strains harboring two simultaneously inactivated acidic protein genes were constructed. None of the six possible double disruptions was lethal, but the simultaneous inactivation of either YP1 alpha and YP1 beta(L44') or YP2 alpha(L44) and YP2 beta(L45) caused an important decrease in the cell growth rate. Ribosomes isolated from these slow-growing strains did not contain acidic proteins, not even the two polypeptides whose genes were still intact, although these proteins were present in the cell extracts and they seem to be able to form high-molecular weight protein complexes. Transformation of a slow-growing double transformant with a plasmid containing one of the disrupted genes restored the presence of the acidic proteins in the ribosomes and normal growth rates. The particles of the slow-growing strains were active in an in vitro amino acid polymerizing system, although their activity could be stimulated by the exogenous addition of the missing proteins. These results indicate that in the absence of either YP1 alpha and YP1 beta(L44') or YP2 alpha (L44) and YP2 beta(L45), the remaining acidic proteins are unable to interact with the ribosome in a stable manner, but that a strong interaction of these ribosomal components with the particle is not an absolute requirement for in vivo and in vitro protein synthesis. PMID- 1601876 TI - A soybean vacuolar protein (P34) related to thiol proteases is synthesized as a glycoprotein precursor during seed maturation. AB - We have examined the synthesis, posttranslational processing, and localization of soybean P34, a member of the papain superfamily. P34 has been identified as a constituent of oil storage organelles or oil bodies isolated from seed lysates and has been assumed to be one of the oil body proteins. Electron microscopic immunocytochemistry with a monoclonal antibody demonstrated that P34 is localized in the protein storage vacuoles but not in the oil bodies. Immunocytochemical observations of partially disrupted seed cells showed that the association of P34 with oil bodies appears to occur as a consequence of cell lysis. In vitro synthesis of P34 results in the formation of a 46-kDa polypeptide that increases to 47 kDa due to core glycosylation by canine microsomes. In vivo synthesis studies in the presence and absence of tunicamycin, an inhibitor of N-linked glycosylation, indicate that pro-P34 is 47 kDa. Since the cDNA sequence of prepro P34 contains a single putative glycosylation site in the precursor domain, we conclude that P34, like a few other vacuolar proteins, is synthesized as a glycoprotein precursor. Pulse-chase experiments showed that the processing of pro P34 to mature P34 occurs in a single step and that this posttranslational cleavage occurs on the carboxyl side of an Asn, which is typical of seed vacuolar proteins. Pro-P34 (47 kDa) is detected in immunoblots of maturing seeds. Analysis of RNA indicates that the P34 genes are expressed only during seed maturation and that the P34 mRNA is related to other thiol protease mRNAs detectable in other organs and plants. Unlike other seed thiol proteases that are synthesized only after seed germination, P34 accumulates during seed maturation. PMID- 1601877 TI - Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. AB - GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids expressed in some normal tissues such as brain and in various tumors such as neuroblastomas, astrocytomas, and malignant melanomas. We used a eukaryotic cell transient expression system to isolate cDNA clones that determine GM2 expression. We developed a new cell line from murine melanoma line B16 by transfecting with the polyoma T antigen gene that was suitable for this purpose. Two cDNA clones, both of which have a continuous open reading frame of 1683 base pairs, were isolated. Although the cloned cDNAs had no primary sequence similarity to reported glycosyltransferases, the deduced amino acid sequence predicted a type II transmembrane protein with an overall structure similar to other glycosyltransferases. The cDNA clones, when stably transfected, determined the expression of GM2 in B16 cells and GM2 and GD2 in the human melanoma line MeWo. Northern blot analysis revealed two transcripts in all cells that expressed either GM2 or GD2 or both. These findings indicate that the cDNAs catalyze the transfer of GalNAc onto GM3 and GD3 by a beta 1,4 linkage, resulting in the synthesis of GM2 and GD2, respectively. Namely they suggest that these cDNAs derive from the UDP-GalNAc: GM3/GD3 beta 1,4 N-acetylgalactosaminyltransferase (EC 2.4.1.92) gene. PMID- 1601878 TI - The yeast SEC17 gene product is functionally equivalent to mammalian alpha-SNAP protein. AB - The SEC17 gene of Saccharomyces cerevisiae is required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus. Here we report that the product of the SEC17 gene has the exact biochemical properties expected for a yeast homologue of the mammalian transport factor, alpha-SNAP. The DNA sequence of SEC17 codes for a protein of predicted molecular mass of 33 kDa. Immunoblotting indicates that Sec17p fractionates as a peripheral membrane protein and is mostly soluble when overexpressed, suggesting the presence of a saturable membrane receptor for Sec17p. Sec17p was purified from yeast cytosol using a SNAP-dependent in vitro mammalian Golgi transport assay. Kinetic analysis using this assay shows Sec17p acts temporally close to the fusion of transport vesicles with the medial Golgi compartment. In yeast extracts, Sec17p binds to Sec18p with a 1:1 stoichiometry. The interaction between Sec17p and Sec18p requires an activity provided by yeast membranes, and this putative membrane receptor activity is not extracted by high salt treatment of membranes. PMID- 1601879 TI - COOH-terminal methylation of lamin B and inhibition of methylation by farnesylated peptides corresponding to lamin B and other CAAX motif proteins. AB - Previous reports from this laboratory have demonstrated that lamin B is reversibly methylesterified in a cell cycle-dependent manner. The site of this methylation, however, was not identified. In this report, we describe a single major methylated product obtained following reversed-phase high-performance liquid chromatographic analysis of peptides generated by proteolytic digestion of lamin B from rat liver nuclear envelopes. This peptide was retained on a lamin B COOH-terminal-specific antibody-affinity column, and COOH-terminal localization was confirmed by amino acid sequencing. Two other COOH-terminal peptides were found but were not methylated and differed in sequence by at least a single residue from the methylated peptide, indicating the existence of two lamin B gene products. Tetrapeptides, representing the putative mature COOH termini of lamin B, K-ras-2A, and unprocessed lamin A, were synthesized with or without farnesyl modification of the COOH-terminal cysteines. All three farnesylated peptides served as substrates for the partially purified lamin B methyltransferase with apparent Km values of 4.5, 0.69, and 21 microM, respectively. Nonfarnesylated peptides were not substrates for the enzyme. The three farnesylated peptides were also effective to varying degrees at inhibiting the methylation of lamin B and other cellular proteins in cell lysates. PMID- 1601880 TI - Initiation of methyl-directed mismatch repair. AB - Escherichia coli MutH possesses an extremely weak d(GATC) endonuclease that responds to the state of methylation of the sequence (Welsh, K. M., Lu, A.-L., Clark, S., and Modrich, P. (1987) J. Biol. Chem. 262, 15624-15629). MutH endonuclease is activated in a reaction that requires MutS, MutL, ATP, and Mg2+ and depends upon the presence of a mismatch within the DNA. The degree of activation correlates with the efficiency with which a particular mismatch is subject to methyl-directed repair (G-T greater than G-G greater than A-C greater than C-C), and activated MutH responds to the state of DNA adenine methylation. Incision of an unmethylated strand occurs immediately 5' to a d(GATC) sequence, leaving 5' phosphate and 3' hydroxy termini (pN decreases pGpAp-TpC). Unmethylated d(GATC) sites are subject to double strand cleavage by activated MutH, an effect that may account for the killing of dam- mutants by 2 aminopurine. The mechanism of activation apparently requires ATP hydrolysis since adenosine-5'-O-(3-thiotriphosphate) not only fails to support the reaction but also inhibits activation promoted by ATP. The process has no obligate polarity as d(GATC) site incision by the activated nuclease can occur either 3' or 5' to the mismatch on an unmethylated strand. However, activation is sensitive to DNA topology. Circular heteroduplexes are better substrates than linear molecules, and activity of DNAs of the latter class depends on placement of the mismatch and d(GATC) site within the molecule. MutH activation is supported by a 6-kilobase linear heteroduplex in which the mismatch and d(GATC) site are centrally located and separated by 1 kilobase, but a related molecule, in which the two sites are located near opposite ends of the DNA, is essentially inactive as substrate. We conclude that MutH activation represents the initiation stage of methyl-directed repair and suggest that interaction of a mismatch and a d(GATC) site is provoked by MutS binding to a mispair, with subsequent ATP-dependent translocation of one or more Mut proteins along the helix leading to cleavage at a d(GATC) sequence on either side of the mismatch. PMID- 1601881 TI - Two immunologically and developmentally distinct chondroitin sulfate proteolglycans in embryonic chick brain. AB - Two different chondroitin sulfate proteoglycans (CSPG) in embryonic chick brain were distinguished by immunoreactivity either with S103L, a rat monoclonal antibody which reacts specifically with an 11-amino-acid region in the chondroitin sulfate domain of the core protein of chick cartilage CSPG (Krueger, R. C., Jr., Fields, T. A., Mensch, J. R., and Schwartz, N. B. (1990) J. Biol. Chem. 265, 12088-12097), or with HNK-1, a mouse monoclonal antibody which reacts with a 3-sulfoglucuronic acid residue on neural glycolipids and glycoproteins (Chou, D. K. H., Ilyas, A., Evans, J. E. Costello, C., Quarles, R. H., and Jungawala, F. B. (1986) J. Biol. Chem. 261, 11717-11725) but not with both antibodies. This specific immunoreactivity was used to separate the two CSPGs for further characterization. The S103L reactive brain proteoglycan had a core protein of similar size to cartilage CSPG (370 kDa) but exhibited a smaller hydrodynamic size (K(av) of 0.308). It was substituted predominantly with chondroitin sulfate chains and virtually no keratan sulfate chains. The HNK-1 reactive CSPG had a smaller core protein (340 kDa), an even smaller hydrodynamic size (K(av) of 0.564), and was substituted with both chondroitin sulfate and keratan sulfate chains. Glycosidase digestion patterns with endo-beta galactosidase, N-glycosidase F, neuraminidase, and O-glycosidase, and reactivity with an antibody to the hyaluronate binding region also showed significant differences between the two brain CSPGs. Expression of the S103L reactive brain CSPG was developmentally regulated from embryonic day 7 through 19 with a peak in core protein on day 13, and in mRNA expression at day 10. In contrast the HNK-1 reactive brain CSPG was constitutively present from day 7 through hatching. These data suggest that these two distinct core proteins are immunologically and biochemically unique translation products of two different CSPG genes. PMID- 1601882 TI - Phosphatidylinositol glycan (PI-G) anchored membrane proteins. Amino acid requirements adjacent to the site of cleavage and PI-G attachment in the COOH terminal signal peptide. AB - Secreted proteins are processed from a nascent form that contains an NH2-terminal signal peptide. During processing, the latter is cleaved by a specific NH2 terminal signal peptidase. The nascent form of phosphatidylinositol glycan (PI-G) tailed proteins contain both an NH2- and a COOH-terminal signal peptide. The two signal peptides have much in common, such as size and hydrophobicity. The COOH terminal peptide is also cleaved during processing. We propose that the amino acid in a nascent protein that ultimately combines with the PI-G moiety be designated the omega site. Amino acids adjacent and COOH-terminal to the omega site would then be omega + 1, omega + 2, etc. In previous studies, we showed that allowable substitutions at the omega site of an engineered form of placental alkaline phosphatase (miniPLAP) are limited to 6 small amino acids. In the present study, mutations were made at the omega + 1 and omega + 2 sites. At the omega + 1 site, processing to varying degrees was observed with 8 of the 9 amino acids substituted for alanine, the normal constituent. Only the proline mutant showed no processing. By contrast, the only substituents permitted at the omega + 2 site were glycine and alanine, with only trace activity observed with serine and cysteine. Thus, just as there is a -1, -3 rule for predicting cleavage by NH2 terminal signal peptidase, there appears to be a comparable omega, omega + 2 rule for predicting cleavage/PI-G addition by COOH-terminal signal transamidase. PMID- 1601883 TI - The Bof protein of bacteriophage P1 exerts its modulating function by formation of a ternary complex with operator DNA and C1 repressor. AB - Bacteriophage P1 encodes several regulatory elements for the lytic or lysogenic response, which are located in the immC, immI, and immT regions. Their products are the C1 repressor of lytic functions with the C1 inactivator protein Coi, the C4 repressor of antirepressor synthesis and the modulator protein Bof, respectively. We have studied in vitro the interaction of the components of the immC and immT regions with C1-controlled operators using highly purified Bof, C1, and Coi proteins. Bof protein (M(r) = 9,800) does not interact with C1 repressor alone, but as shown by DNA mobility shift experiments, in the presence of C1 repressor Bof binds to all operators tested by forming a C1.Bof-operator DNA ternary complex. The effect of this complex formation was studied in more detail with the operator of the c1 gene. Here, Bof only marginally alters the C1 repressor footprint at Op99a,b, but nevertheless considerably influences the repressibility of the operator.promoter element: (i) the autoregulated c1 mRNA synthesis is further down-regulated and (ii) the ability of Coi protein to dissociate the C1.operator DNA complex is strongly inhibited. We suggest that Bof protein functions by modulating C1 repression of many widely dispersed operators on the prophage genome. PMID- 1601884 TI - Mutational analysis of the structure and function of the xeroderma pigmentosum group A complementing protein. Identification of essential domains for nuclear localization and DNA excision repair. AB - We showed previously that the xeroderma pigmentosum group A complementing (XPAC) protein involved in the DNA excision repair pathway contains a zinc-finger motif and is localized in the nucleus of normal human cells. For detailed structural and functional analyses of the XPAC protein, we constructed various XPAC cDNAs by site-directed mutagenesis and isolated permanent cell lines expressing mutant proteins. Immunofluorescent analysis of these lines indicated that the nuclear localization signal is located in the region encoded by Exon 1, especially centered at amino acids 30-42. A UV survival study showed that regions from Exons 2 through 6 were essential for DNA repair function, but that Exon 1 was not. Interestingly, deletion of the glutamic acid cluster in the region encoded by Exon 2 resulted in a dramatic loss of DNA repair activity. Furthermore, replacements of each of the 4 cysteines supposed to form a zinc-finger structure in the region encoded by Exon 3 by serine or glycine resulted in similar levels of loss of repair activity. These results suggest that all 4 cysteines forming a zinc-finger structure and also the glutamic acid cluster are important for DNA repair function. PMID- 1601885 TI - Molecular structure and function of the porcine arachidonate 12-lipoxygenase gene. AB - The gene encoding arachidonate 12-lipoxygenase was cloned from a porcine EMBL3 genomic library using a cDNA probe of the enzyme, and its nucleotide sequence was determined. The gene consists of 14 exons with 13 introns, and spans approximately 8 kilobases. Analysis of splice junctions indicated that all of the splice donor and acceptor sites conformed to the GT/AG rule. An approximately 1 kilobase region upstream of the coding sequence contains nine GC-boxes for potential Sp1-binding sites at positions -77, -135, -145, -165, -214, -636, -643, -684, and -813. There are two sets of AP-2 binding sequence at positions -234 and -402. Neither typical TATA box nor CCAAT box is found in this region. The transcriptional start site was determined by primer extension analysis, and was tentatively identified as a cytidine residue located 19 bases upstream from initiation codon. Southern blot analysis revealed the presence of one copy of 12 lipoxygenase gene per haploid genome. We found striking similarities in genomic organization as well as the promoter sequences between the porcine 12 lipoxygenase and the rabbit 15-lipoxygenase genes, suggesting that these genes are evolutionarily related. PMID- 1601886 TI - Thrombospondin 3 (Thbs3), a new member of the thrombospondin gene family. AB - A third member of the thrombospondin gene family (Thbs3) has been partially characterized in the mouse. In both the mouse and humans, the Thbs3/THBS3 gene is located immediately upstream from the Muc1/MUC1 (episialin) gene; less than 3 kilobases separate the polyadenylation signal of one gene from the start of transcription of the other. The available coding sequence in Thbs3 shows a high degree of amino acid sequence identity to Thbs1 and Thbs2 (58 and 59%, respectively, in exons 15 and 16), but the exon/intron organization of Thbs3 appears to be more disparate than that of the two previously described members of the family. The shorter length of the Thbs3 mRNA (3.5 kilobases) can be attributed largely to a shorter 3'-untranslated region. The Thbs3 gene is expressed in a distinctive pattern in mouse tissues, with the highest level of expression in lung. This pattern suggests a unique function for the translation product of the Thbs3 gene. PMID- 1601887 TI - Regulatory sequences and protein-binding sites involved in the expression of the rat plasminogen activator inhibitor-1 gene. AB - Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor that inhibits both tissue-type and urokinase-type plasminogen activators. Expression of PAI-1 is regulated by growth factors, cytokines, and hormones. To determine the molecular mechanisms involved in the basal expression of the rat PAI-1 gene, we have analyzed the cis-acting sequences and the trans-acting factors involved in the transcription of this gene in the HTC rat hepatoma cell line. DNase I protection analyses revealed eight regions within the first 764 base pairs of 5' flanking sequence that interact specifically with HTC cell nuclear proteins. The proteins that bind to five of the eight footprinted sites were identified as PEA3 , Sp1-, and CTF/NF-1-like proteins using competition electrophoretic mobility shift assays. The expression of fusion genes containing progressive 5' deletions of the rat PAI-1 promoter linked to the chloramphenicol acetyltransferase reporter gene were analyzed in transient transfection experiments in HTC cells. These studies demonstrated the Sp1 and CTF/NF-1 sites to be important for transcriptional activation. Two of the footprinted sites contain the sequence 5' TTTGn(n)TCAAT-3' and were shown in competition electrophoretic mobility shift assays to bind the same or related protein(s). Sequences containing these sites, from -764 to -628 base pairs, and from -266 to -188 base pairs, were identified in functional studies as repressor elements of transcription. PMID- 1601888 TI - Monensin and brefeldin A differentially affect the phosphorylation and sulfation of secretory proteins. AB - Chromogranin B and secretogranin II, two members of the granin family, are known to be post-translationally modified by the addition of O-linked carbohydrates to serine and/or threonine, phosphate to serine and threonine, and sulfate to carbohydrate and tyrosine residues. In the present study, chromogranin B and secretogranin II were used as model proteins to investigate in which subcompartment of the Golgi complex secretory proteins become phosphorylated. Monensin, a drug known to block the transport from the medial to the trans cisternae of the Golgi stack, inhibited the phosphorylation of the granins, indicating that this modification occurred distal to the medial Golgi. Monensin also blocked the addition of galactose to O-linked carbohydrates and the sulfation of the granins, confirming previous data that these modifications take place in the trans Golgi. To distinguish, within the trans Golgi, between the trans cisternae of the Golgi stack and the trans Golgi network, we made use of the previous observation that brefeldin A results in the redistribution to the endoplasmic reticulum of membrane-bound enzymes of the trans cisternae of the Golgi stack, but not of the trans Golgi network. Brefeldin A treatment abolished granin sulfation but resulted in the accumulation of phosphorylated and galactosylated granins. Differential effects of brefeldin A on membranes of the Golgi stack versus the trans Golgi network were also observed by immunofluorescence analysis of marker proteins specific for either compartment. Our results suggest that the phosphorylation of secretory proteins, like their galactosylation, largely occurs in the trans cisternae of the Golgi stack, whereas the sulfation of secretory proteins on both carbohydrate and tyrosine residues takes place selectively in the trans Golgi network. PMID- 1601889 TI - Biophysical characterization of involucrin reveals a molecule ideally suited to function as an intermolecular cross-bridge of the keratinocyte cornified envelope. AB - Involucrin is a 68-kDa precursor of the keratinocyte cornified envelope. During keratinocyte terminal differentiation glutamine residues of involucrin become covalently cross-linked to other envelope precursors via covalent epsilon-(gamma glutamyl)lysine bonds. In the present study we examine the secondary and tertiary structure of human involucrin using computer algorithms, circular dichroism, and electron microscopy. Our results indicate that involucrin is an extended, flexible, rod-shaped molecule that has a length of 460 A, an axial ratio of 30:1 and possesses between 50 and 75% alpha-helical content. Glutamine residues are circumferentially distributed along the length of the alpha-helical segments of the molecule, a distribution that is conserved in all species. We hypothesize that this distribution of glutamine residues together with the elongated shape of the molecule permits optimal interaction of involucrin glutamyl side chains with the lysine residues of other para-membranous proteins during transglutaminase mediated cross-linking. Moreover, its long length allows involucrin to cross-link molecules that are separated by substantial distances in the cornified envelope. These properties allow a single involucrin molecule to form multiple cross-links, in multiple spatial planes, with other envelope precursors. Thus, the structure of involucrin is that of an ideal intermolecular cross-bridge. PMID- 1601890 TI - Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) bind to a multi-SNAP receptor complex in Golgi membranes. AB - Soluble N-ethylmaleimide-sensitive fusion attachment proteins (SNAPs) are required for the binding of N-ethylmaleimide-sensitive fusion protein (NSF) to Golgi membranes and are, therefore, required for intra-Golgi transport. We report the existence of distinct alpha/beta-SNAP and gamma-SNAP-binding sites in Golgi membranes that appear to be part of the same receptor complex. Cross-linking studies with alpha-SNAP demonstrate that an integral membrane protein of between 30-40 kDa is the alpha-SNAP binding component of the multi-SNAP receptor complex. These data suggest that SNAPs function by independently binding to a multi-SNAP membrane-receptor complex, thereby activating them to serve as adaptors for the targeting of NSF. PMID- 1601891 TI - The binding specificity of normal and variant rat Kupffer cell (lectin) receptors expressed in COS cells. AB - A receptor uniquely found on the surface of rat Kupffer cells was shown previously to bind oligosaccharides terminating in galactose, N acetylgalactosamine, and fucose. To analyze further the binding specificity of the receptor, receptor-mediated adhesion of transfected COS cells to immobilized glycolipids of known structure was measured. The glycolipid Gb4Cer (GalNAc beta 1 3Gal alpha 1-4Gal beta 1-4Glc beta 1Cer) was the best ligand. Gb5Cer (GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc beta 1Cer) and LacCer (Gal beta 1-4Glc beta 1Cer) bound more weakly (five times less than Gb4Cer) and Gb3Cer (Gal alpha 1-4Gal beta 1-4Glc beta 1Cer), and g3Cer(GalNAc beta 1-4Gal beta 1 4Glc beta 1Cer) bound even more weakly (60 times less than Gb4Cer). Gangliosides did not support adhesion of transfected cells. The adhesion of COS cells transfected with plasmids encoding variants of the receptor was also examined. In each variant, either tryptophan 498 or 523, which are conserved in most C-type lectins, was replaced by one of several amino acids. Variants that retained binding activity had the same specificity as the normal receptor. Differences between variants were noted, however, in maximal levels of adhesion and these differences correlated with altered expression of the receptor variants in COS cells. PMID- 1601892 TI - A new alpha-helical coiled coil protein encoded by the Salmonella typhimurium virulence plasmid. AB - A new protein of Salmonella typhimurium was identified and characterized. The gene (tlpA) encoding this protein (TlpA) was isolated from the large virulence associated plasmid of S. typhimurium and sequenced in order to predict the primary structure of TlpA. tlpA encodes a 371-amino acid soluble protein with a calculated M(r) of 41600 and pI of 4.63. Secondary structure predictions and sequence statistics of TlpA indicated a predominant alpha-helical configuration and presence of heptapeptide repeat motifs characteristic of coiled coil proteins. Purified TlpA was shown to have biochemical properties similar to those of coiled coil proteins, including adoption of an alpha-helical configuration and a tendency to form homodimers. Furthermore, TlpA possessed heat resistance, evidence for a chain register and altered mobility in urea/sodium dodecyl sulfate polyacrylamide gel electrophoresis gels which are characteristics of tropomyosins. TlpA shows 32% overall sequence similarity with rat cardiac myosin and 36% similarity with horse platelet beta-tropomyosin over 226 residues, whereas selected regions possessed significant sequence identities with myosins, tropomyosins, and alpha-helical surface proteins of Streptococcus pyogenes. Our results indicate that TlpA represents a new member of prokaryotic coiled coil proteins. PMID- 1601893 TI - The unprocessed C-terminal dipeptide of recombinant beta-nerve growth factor determines three stable forms with distinct biological activities. AB - The processing of polypeptide neurotrophins in the nervous system is poorly understood. In this paper, we provide information on the effects of C-terminal processing of nerve growth factor. Three forms of recombinant mouse beta-nerve growth factor (rNGF) were produced and isolated from insect cells infected with a recombinant baculovirus. The three purified forms of rNGF exhibited distinct biological activities and differed in their abilities to compete with high affinity binding of mouse beta-nerve growth factor (mNGF). However, they were chemically and structurally indistinguishable from each other. All three forms of rNGF differed from mature mNGF from mouse submaxillary gland in that the C terminal Arg-Gly dipeptide had not been proteolytically removed. Removal of the C terminal dipeptide by gamma-NGF peptidase treatment converted the three forms into a single form identical with mature mNGF. The above results demonstrate that a single polypeptide of rNGF, due to the presence of a C-terminal dipeptide, exhibits three stable dimeric protein conformations with distinct biological activities. The apparent lack of gamma-NGF peptidase in the nervous system raises the possibility that the biologically significant form of NGF may differ from mature mNGF; such a difference may be of physiological relevance. PMID- 1601894 TI - Modulation of the physical state of cellular cholesteryl esters by 4,4' (isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol). AB - The effect of 4,4'-(isopropylidenedithio)bis(2,6-di-t-butylphenol) (probucol) on cholesteryl ester physical state was examined in dry mixtures, phospholipid containing dispersions, and cells. Probucol has little effect on the solid to isotropic transition of cholesteryl oleate, but broadens and decreases the enthalpy of the liquid-crystalline transitions at concentrations as low as 1-2 mol %. A probucol transition is only observed at concentrations greater than 20 mol %. The mesomorphic phases of the cholesteryl oleate/probucol mixtures were identified by visual inspection and polarized light microscopy. Mixtures are liquid at probucol concentrations in excess of 5 mol % at 37 degrees C. Probucol also dramatically reduces the enthalpy of the liquid-crystalline transitions of the cholesteryl oleate core of dispersions of the ester with phospholipids at a concentration of 10 mol %, reducing the enthalpy by greater than 80% and the transition temperatures by approximately 2 degrees C. The phase state of cholesteryl esters in Fu5AH rat hepatoma cells was examined after incubation with cholesterol/phospholipid dispersions that caused the accumulation of anisotropic cholesteryl ester droplets. Differential scanning calorimetry scans of cells incubated with cholesterol-rich phospholipid dispersions indicated a phase transition near 48 degrees C, which was abolished when the cells were co incubated with 50-100 micrograms/ml of probucol in the loading medium. Subsequent to the formation of isotropic cholesteryl ester droplets in the presence of probucol, the rate of efflux of cholesterol from the cells to phosphatidylcholine containing acceptors in the medium was increased. These data show that probucol is relatively soluble in cholesteryl esters and that probucol changes the phase state of cholesteryl ester droplets in cells to a more fluid phase in which the cholesteryl esters are more readily mobilized. PMID- 1601895 TI - A 35-kDa protein binding to a cytosine-rich strand of hypervariable minisatellite DNA. AB - A minisatellite-binding protein, Msbp-4, with a molecular mass of 35 kDa has been purified from mouse tumor cells that binds to hypervariable Pc-1 and Pc-2 minisatellites. The binding is much more efficient than that to genetically stable minisatellite homologues. As assayed by Southwestern analysis, Msbp-4 favors multiple copies of the Pc-2 repeat sequence GGCAGGA and requires the cytosine-rich single strand for the binding. The activity is also present in extracts from mouse testis but not from liver. The phosphatase treatment revealed that Msbp-4 is phosphorylated and may have a regulatory function, because dephosphorylation affects the activity and specificity of the binding. Sequence preference is demonstrated by a competition experiment using single-base substitution mutants. Thus, the binding properties of Msbp-4 observed here lead to an implication that the protein-DNA complexes result in formation of a single stranded DNA loop of the G-rich strand in the minisatellite which may enhance the ability of the minisatellite to undergo recombination. PMID- 1601896 TI - Molecular recognition sites on factor Xa which participate in the prothrombinase complex. AB - Coagulation factor X, when activated to factor Xa by proteolytic cleavage, itself becomes an active serine protease which participates as a component of the macromolecular prothrombinase complex along with factor Va, phospholipid, and calcium ions. To identify specific structural regions on factor Xa responsible for mediating its function in activating prothrombin, we used 21 synthetic peptides corresponding to 65% of the primary structure of factor X as potential inhibitors of prothrombin activation. Using purified components, thrombin formation was inhibited by seven peptides in a dose-dependent noncompetitive manner. Antibodies to selected inhibitory peptides affinity purified on a factor Xa-agarose column inhibited thrombin formation in a dose-dependent manner, indicating that the corresponding regions on factor Xa are surface-exposed. Kinetic analyses varying the order of reagent addition suggested that peptides 211-222, 254-269, and 263-274 were highly effective in preventing the factor Xa factor Va interaction. Peptides 275-287 and 415-425 were considered to derive from a distal region involved in substrate binding, based upon mixed inhibition kinetic analyses and assuming that inhibitory peptides not inhibitory in factor Va binding are related to a specific region of substrate interaction. Cross linking studies confirmed that peptides 263-274 and 263-276 could bind specifically to the light chain of factor V/Va. These findings provide the basis for further pursuing the precise definition of interactive sites on factor Xa using site-directed mutagenesis and molecular modeling. PMID- 1601897 TI - Prostaglandin endoperoxide synthase. The aspirin acetylation region. AB - Aspirin selectively acetylates Ser-530 of prostaglandin endoperoxide (PGH) synthase-1. This causes inactivation of the cyclooxygenase activity of the enzyme, but does not appreciably affect its peroxidase activity. Although the aspirin-acetylated enzyme is inactive, we found that PGH synthase-1 in which Ser 530 had been replaced with an alanine was catalytically active; accordingly, we proposed that aspirin inhibits cyclooxygenase activity by placing a larger than normal side chain at position 530 thereby interfering with arachidonate binding (DeWitt, D.L., El-Harith, E. A., Kraemer, S. A., Andrews, M. J., Yao, E. F., Armstrong, R. L., and Smith, W. L. (1990) J. Biol. Chem. 265, 5192-5198). As a further test of this hypothesis we have used site-directed mutagenesis and transient expression in cos-1 cells to prepare and characterize five additional substitutions of Ser-530. Consistent with our proposal, the presence of amino acids with bulky side chains at position 530 inhibited cyclooxygenase activity and decreased the apparent affinity of the enzyme for arachidonate. In related work, we characterized a series of mutant PGH synthases-1 having substitutions at residues adjoining Ser-530, including Phe-529, Leu-531, Lys-532, and Gly-533, in order to evaluate the contributions of each residue to cyclooxygenase catalysis. The most significant conclusion of this part of the study is that residues 529 533 all are important for the peroxidase activity as well as the cyclooxygenase activity of PGH synthase-1. Phe-529, in particular, was found to be critical for PGH synthase-1 structure and catalysis; some substitutions at this position led to the production of proteins lacking about 100 amino acids from their COOH termini. PMID- 1601898 TI - Glow discharge plasma deposition of tetraethylene glycol dimethyl ether for fouling-resistant biomaterial surfaces. AB - The glow discharge plasma deposition (GDPD) of tetraethylene glycol dimethyl ether is introduced as a novel method for obtaining surfaces that are resistant to protein adsorption and cellular attachment. Analysis of films by x-ray photoelectron spectroscopy and several biological assays indicate the formation of a fouling-resistant, PEO-like surface on several substrata (e.g., glass, polytetrafluoroethylene, polyethylene). Adsorption of 125I-radiolabelled proteins (fibrinogen, albumin and IgG) from buffer and plasma was very low (typically less than 20 ng/cm2) when compared to the untreated substrata, which exhibited much higher levels of protein adsorption. Not all coated substrata adsorbed equal amounts of protein (e.g., coated glass samples typically adsorbed more protein than coated polyethylene or coated polytetrafluoroethylene samples), suggesting that the substratum used may affect the amount of protein adsorbed. Measurement of dynamic platelet adhesion, using epifluorescent video microscopy, and endothelial cell attachment further demonstrates the short-term nonadhesiveness of these surfaces. PMID- 1601899 TI - Protein adsorption of biomedical polymers influences activated monocytes to produce fibroblast stimulating factors. AB - The studies presented in this manuscript were based upon the hypothesis that monocytes/macrophages selectively produce cytokines and growth factors due to their interactions with polymers and proteins which are adsorbed to their surfaces. These factors in turn selectively influence the ability of fibroblasts to proliferate. The factors which influence fibroblast proliferation were released from monocytes incubated with polymers: Biomer, polydimethylsiloxane (PDMS), polyethylene (PE), expanded polytetrafluoroethylene (ePTFE), Dacron, and control polystyrene with and without preadsorption with physiological concentrations of IgG, fibrinogen, fibronectin, hemoglobin, or albumin. No simple correlation was found between adsorbed protein, biomedical polymer, and the ability of monocytes to produce growth factors and cytokines which influence fibroblast proliferation. This is evidence for selective protein-polymer interactions which in turn selectively activate monocytes to produce variable cell cycle competence and progression factors controlling fibroblast growth. PMID- 1601900 TI - Preparation of poly (D,L) lactide microspheres by emulsion-solvent evaporation, and their clinical applications as a convenient embolic material. AB - The aim of preoperative embolization is to facilitate surgical removal by reducing tumor volume and vascularity, thereby decreasing blood loss during surgery. In a search for a better embolic material, compared to heterogeneous commercial products, we describe here in detail the preparation of poly (D,L) lactide microspheres by an emulsion-solvent evaporation process. The size distribution of the microparticles and their aggregation state--critical parameters in view of such application--have been investigated. Their effectiveness, as an embolic material, has been evaluated by some preliminary experiments undertaken on humans. The results were assessed on clinical and histological grounds. PMID- 1601901 TI - Mechanical properties of fibrin adhesives for blood vessel anastomosis. AB - Various methods have been used for anastomosing, or attaching, two ends of a severed blood vessel together. The most common method, suturing, is tedious, can be time-consuming, and requires special training in microvascular surgery. Other methods, such as mechanical devices and lasers, have some problems as well. The use of fibrin adhesives for blood vessel anastomosis might eliminate some of the current problems by allowing a quicker, simpler, and more reliable method of attachment. Although mechanical studies have been conducted to determine fibrin glue properties in shear, tensile, and burst tests; most of these studies have used skin or intestinal tissue. Therefore, to evaluate the feasibility of using fibrin glue as an adhesive for blood vessel anastomosis, the mechanical properties of blood vessels joined with fibrin glue were examined using tensile and burst tests. High and low fibrinogen concentrations were tested after 5- or 45-min time periods. In addition, three clinical methods of attachment were compared: end-to-end anastomosis, vessel overlapping, and suturing. In this study, because the adhesive strength was not found to increase significantly after 5 min, setting times for fibrin glue may be short enough to make it a clinical option when compared to suturing. In addition, the higher fibrinogen concentration did not result in a significantly higher adhesive strength, indicating that the lower concentration fibrin adhesives may be of comparable strength to the higher concentrations for clinical applications. PMID- 1601903 TI - Human gingival tissue response to HTR polymer. AB - Biopsies secured during reentry surgical evaluation of previously treated periodontal osseous defects were examined for gingival tissue response to HTR polymer. Eleven patients provided biopsies of HTR grafted sites 6-7 months after initial implantation. Minimal inflammation and infrequent foreign body giant cells were found. Bone was present in about half of the samples and osteogenesis associated with the HTR graft material was seen in about 20% of the biopsies. Serendipitously, biopsies of other graft materials or debridement only sites from 6-30 months post-treatment were also available for analysis and comparison, and showed similar tissue response. The results of this study suggest that HTR polymer (and other graft materials) is very biocompatible and elicits no untoward gingival tissue responses when placed in periodontal osseous defects. PMID- 1601902 TI - The role of connective tissue in inhibiting epithelial downgrowth on titanium coated percutaneous implants. AB - Ideally, the surface of epithelium-penetrating implants should impede apical epithelial migration. Previous studies have shown that micromachined grooved surfaces can produce connective-tissue ingrowth, which inhibits epithelial downgrowth on percutaneous implants [Chehroudi et al., J. Biomed. Mater. Res., 24, 9, (1990)]. However, in those studies, connective tissue and epithelium interacted with the same surface so that the effects of the surfaces on each population could not be determined separately. The objectives of this study were (a) to examine cell behavior on implants in which connective tissue contacted surfaces of various topographies and epithelium encountered only a smooth surface, and (b) to compare one-stage and two-stage surgical techniques. Implants had a base component (BC) which was either smooth or had a surface with 19-micron or 30-micron-deep grooves or 120-micron-deep tapered pits, and a skin penetrating component (SPC) which was smooth. In the two-stage technique, the BC was implanted subcutaneously for 8 weeks, which permitted the healing of the peri implant connective tissue. In the second stage the SPC was connected to the BC. For one-stage implants, BC & SPC were connected and implanted percutaneously. Implants (BC & SPC) were removed 1, 2, or 3 weeks after percutaneous implantation and histological sections were measured for recession, connective tissue and epithelial attachment as well as capsule thickness. Light microscopy indicated that both grooved and tapered pitted surfaces encouraged connective tissue ingrowth. On the grooved surfaces, the orientation of fibroblasts changed from an oblique to a more complex pattern which included cells having round nuclei within the grooves, as well as cells oriented oblique or perpendicular to the grooves. In the tapered pits a hammock-like arrangement of fibroblasts was observed. In some cases, foci of mineralization and formation of bonelike tissue were found on the grooved and pitted surfaces. The apical migration of the epithelium was significantly (p less than 0.05) inhibited by those micromachined surfaces which produced connective tissue ingrowth to the BC. This study found that placing the implants in two stages improved the performance of percutaneous devices, and that a further improvement was achieved if the implant had a surface promoting connective tissue ingrowth. PMID- 1601904 TI - High-voltage electron microscopy and conventional transmission electron microscopy of the interface zone between bone and endosteal dental implants. AB - The interface between mandibular bone and endosteal dental implants was examined with an in vivo dog model. Undecalcified mandibular implant samples were observed with both conventional transmission electron microscopy and high-voltage transmission electron microscopy (HVEM). Results demonstrated the variable nature of the interfacial support tissues. Mineralized bone was often found within 50 nm of the implant surface, separated from that surface only by an electron dense deposit. Osteocytes were observed close to the interface encased within lacunae extending numerous cellular processes through canaliculi. An osteoblast was also observed directly at the interface within a developing lacuna. Other interfacial areas exhibited a finely fibrillar and more electron lucent morphology. Furthermore, other areas were shown to be composed of wider zones of extracellular products containing collagen fibrils, ground substance, and calcified inclusions. Because bone is an actively growing and remodeling tissue, these different morphological zones around the entire area of the implants would appear to confirm the dynamic tissue response to endosteal dental implants. Further, HVEM stereology was shown to be an exciting research tool to investigate this tissue response. PMID- 1601905 TI - Biotinylation of implantable collagen for drug delivery. PMID- 1601906 TI - Aortic valve replacement in children under 16 years of age with congenital or rheumatic valvular disease. A study of 64 cases. AB - Sixty-four children have had a single aortic valve replacement under 16 years of age, 50 for rheumatic disease (47) or bacterial endocarditis (3) (group I) and 14 for a congenital aortic valve lesion (group II), 38 were disk prostheses and 26 were ball prostheses. Associated procedures had to be performed 31 times, with widening of a small aortic annulus by a patch in 7 patients. The early mortality was 12.5%. Of 56 survivors, 55 were followed postoperatively for a mean period of 7 years (group I: 44, group II: 11). Forty of the 55 patients were anticoagulated (correctly maintained in only 24 patients), 15 were not anticoagulated. A high rate of late complications was observed. Thrombo-embolic accidents in 5 patients with inefficient anticoagulant treatment, 2 haemorrhagic episodes, 7 prosthetic leaks; specific problems related to this group of young patients were: recurrence of rheumatic fever with increasing severity of mitral valve disease requiring mitral valve replacement in 5 patients and outgrowth of the prosthesis, which affected 7 patients; this complication is the result of either fibrous deposit around the valve annulus or such a small annulus that the surgeon could only implant a small prosthesis. Ten patients required 11 reoperations for various reasons. The main reason for reoperation was mitral valve replacement for worsening of mitral valve disease caused by recurrence of rheumatic fever. A high late mortality 10/55 (18%) was noted. The main cause of death was a perivalvular leak (5); 1 late death was caused by a stenotic number 17 Bjork-Shiley valve.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601907 TI - Dissecting aneurysms of the ascending aorta occurring late after aortic valve replacement. AB - In 4 patients who had undergone aortic valve replacement, a dissection of the ascending aorta appeared between 7 and 16 years later (mean 12 years). This is a rare complication, occurring in less than one percent of cases. Three cases of aortic regurgitation and one of aortic stenosis developed, and 3 of the cases had dilatation of the ascending aorta and hypertension. The symptoms of dissection were accompanied by signs of either the superior vena caval syndrome or compression of the pulmonary artery. The diagnosis was confirmed by echography and by CT scan. Despite the advances made in the surgery of dissection the prognosis was serious, and 2 of the 4 patients died. Avoidance of this complication depends on replacement of the ascending aorta (composite tube or supracoronary graft according to the involvement of the sinuses of Valsalva) as soon as the diameter of aorta exceeds 55 mm. In cases of moderate dilatation (45 50 mm), systemic reinforcement with Dacron mesh has been shown to have long-term effectiveness. PMID- 1601908 TI - Early extubation after coronary artery bypass surgery: effects on oxygen flux and haemodynamic variables. AB - The effect of extubation within the first postoperative hour was evaluated in 13 patients (mean +/- SD age 59 +/- 6 years) undergoing elective coronary artery bypass surgery without active systemic hypothermia. The mean cardiopulmonary bypass time was 50 +/- 14 minutes. Postoperative improvements in cardiac index and oxygen uptake (from 2.0 +/- 0.4 l/min/m2 and 144 +/- 26 ml/min postinduction to 2.88 +/- 0.76 l/min/m2 and 229 +/- 104 ml/min, p less than 0.01) were maintained following extubation. Lower postoperative systemic and pulmonary vascular resistances (p less than 0.01) did not change to a significant extent following extubation. Despite a two-fold rise in the intrapulmonary shunt (Qs/Qt) following surgery (18.5 +/- 9.7% vs 9.6 +/- 3.2% before surgery) the immediate post-extubation value was similar (18.8 +/- 8.2%) and all patients were discharged from the cardiac recovery area within 16 hours without complication. Extubation within the first postoperative hour is a safe procedure following elective coronary artery surgery with short bypass times where sustained hypothermia less than 32 degrees C is avoided. PMID- 1601909 TI - Results of coronary artery surgery in young adults. AB - To study the results of bypass surgery in young adults, 221 patients undergoing myocardial revascularisation aged 40 or less (1979-1989) were reviewed. The study included 200 men and 21 women. Mean age was 36.2 years. Risk factors were essentially cigarette smoking (69.6%) and hyperlipidaemia (52%). One-hundred and eighteen patients (53.4%) had a history of previous myocardial infarction (MI) and 16 were operated on after an episode of preinfarction angina. One-hundred and twenty-nine patients had three-vessel disease, 59 had double-vessel disease and 33 single-vessel disease. Twenty-three had left main stem coronary artery lesions. Four-hundred and forty-six saphenous vein grafts and 79 internal mammary artery grafts were performed, an average of 2.3 grafts per patient. Operative mortality was 2.7% (6 patients). Deaths were caused in 4 cases by MI. Twelve patients (5.5%) had a non fatal perioperative MI. One-hundred and ninety-nine patients were followed up for a mean of 7.4 years (4838 patients-years). Seventeen late deaths occurred. Six were from cardiac causes. Overall survival was 84% at 9 years. Five patients underwent cardiac reoperation at a mean interval of 6.4 years after the primary procedure. Eighty-five% of patients were free of angina and 11.5% were in an improved condition. In conclusion, coronary revascularisation can be performed at a reduced risk in younger patients. Long term prognosis seems similar to that of the overall group of patients undergoing bypass surgery. PMID- 1601910 TI - Pulmonary valve endocarditis during puerperal sepsis. AB - A case of pulmonary valve endocarditis caused by Staphylococcus aureus during puerperal sepsis in a female patient is reported. The M-mode and two dimensional echocardiographic finding are described. A review of the literature shows that this entity is rare. A large vegetation in the leaflet of the pulmonary valve was excised and the patient recovered after a full course of antibiotics. PMID- 1601911 TI - Limited acute dissections of the abdominal aorta. Report of five cases. AB - Within a two year period, the diagnosis of acute dissection of a segment of the abdominal aorta was made in five cases without aneurysmal dilation or leakage and with virtually no ischaemia. All patients presented with an atypical painful abdominal syndrome and the diagnosis was made by computed tomography. Only one patient, suffering persistent pain was treated by resection and graft interposition of the infrarenal aorta. All the others were treated conservatively and kept under close follow-up. Two of them died from intercurrent disease. The remaining three patients are doing well after 30 and 42 months conservative treatment and 43 months after surgery respectively. A non-complicated dissection of the abdominal aorta must be considered in the differential diagnosis of atypical painful abdominal syndromes. In cases of persistent pain, progression, ischaemia, aneurysmal dilatation or leakage, surgical treatment is mandatory. In uncomplicated cases conservative treatment is recommended, similar to the principles of management for dissections of the descending thoracic aorta. PMID- 1601912 TI - Intermittent obstruction of the Omnicarbon-valve prosthesis in the mitral position due to interference by papillary muscle. Diagnostic and surgical considerations. AB - The frequency of prosthetic heart valve malfunction caused by intrinsic factors has been markedly decreased by refinements of prosthetic design and by improved quality of the prosthetic material. Nevertheless, a variety of extrinsic factors, i.e. thrombus formation, bacterial endocarditis, inadequate suture technique and papillary muscle entrapment, are known to be responsible for mechanical malfunctions of prosthetic heart valves, occasionally leading to sudden cardiac death. In this report, a case of intermittent entrapment of papillary muscle in the Omnicarbon valve is presented; diagnostic and surgical aspects are discussed. PMID- 1601913 TI - Carotid bifurcationplasty: an alternative to patching. AB - Patching of carotid endarterectomies has been advocated as a means of both facilitating secure closure and minimizing recurrent stenosis. Most vascular surgeons occasionally, if not always, patch selected carotid arteries. However, patching requires the surgeon to utilize either prosthetic material (Dacron or PTFE), which is relatively thrombogenic, or autogenous vein, which requires a second operative field and available saphenous vein at the ankle. Bifurcationplasty, otherwise known as bifurcation advancement, has been used as an alternative to patching at our institution over the past four years. This technique, which involves the use of the opened, endarterectomized external carotid artery as an autogenous in-continuity patch for the internal carotid artery, obviates the need for prosthetic materials and saphenous vein alike. This procedure has been performed 30 times over a 4-year period (1987-91). During this time, 280 carotid endarterectomies were performed. A vein patch or Dacron was used in four cases early in this series. Bifurcationplasty was also the procedure of choice for repeat carotid endarterectomy, and was performed in five cases of recurrent stenosis after direct closure. In a follow-up period averaging 22 months (range 1-48), there were no instances of symptomatic restenosis. We feel that bifurcationplasty is an easily performed autogenous alternative to conventional patch closure of the carotid artery. PMID- 1601914 TI - Carotid endarterectomy under hypothermic extracorporeal circulation: a method of brain protection for special patients. AB - This study was undertaken to evaluate the efficacy of hypothermic extracorporeal circulation for cerebral protection in 17 patients having simultaneous carotid endarterectomy and cardiac operations. The cardiopulmonary by-pass (CPB) was conducted using total hemodilution. The body temperature was cooled to 25 degrees C and the heart was arrested with cardioplegic solution. The carotid endarterectomy was performed first followed by the cardiac operation. No neurological or cardiac complications occurred. These results support the reliability of hypothermic cardiopulmonary bypass as a method of providing cerebral protection during simultaneous cardiac and carotid surgical procedures. PMID- 1601915 TI - External carotid artery revascularization: indications, operative techniques and results. AB - The external carotid artery (ECA) is an important collateral pathway in patients with ipsilateral internal carotid artery (ICA) occlusion and recurrent symptoms. An ipsilateral ECA revascularization can improve cerebral perfusion or eliminate an embolic source. In the past 11 years 11 patients underwent operation, 6 times for amaurosis fugax and 5 times for transient ischaemic attacks. Eight times ECA endarterectomy was performed for stenosis and/or ulceration. Eight times closure or separation of the ICA stump with thrombus was carried out. There were no perioperative neurological deficits or deaths, with the exception of 3 patients who already had a long-standing deficit due to the ICA occlusion. All patients were relieved of their ocular or hemispheric symptoms in a follow-up period of 8 years. Two late strokes occurred after 1 1/4 and 4 years. Ipsilateral ECA revascularization is an effective and safe operation and has good long-term results. PMID- 1601916 TI - Atherosclerotic disease of the innominate artery: current management and results. AB - Arterial repair through a sternotomy has long been considered the procedure of choice for innominate artery atherosclerotic disease. Of 22 patients presenting with 21 occlusive lesions and one aneurysm, 17 patients underwent a bypass procedure, and two, an endarterectomy through a sternotomy, whereas three patients underwent cervical procedures. Their postoperative course was uneventful. Early and late results were satisfactory. We conclude that in patients with innominate artery atherosclerotic disease, the procedure employed depends on both the type of lesion and the clinical status of the patient. In most cases, a bypass graft via a sternotomy is the best option, since endarterectomy is not always possible and risks an aortic tear or dissection. In selected cases, balloon angioplasty performed either percutaneously, combined with cerebral protection by an occlusive balloon in the carotid artery or through a carotid arteriotomy in order to flush out embolic material may be sufficient. A by-pass graft from the right to the left common carotid artery is the best procedure in patients with neurological symptoms when angioplasty seems inappropriate, and when sternotomy is contraindicated for either reasons of poor health or a prior mediastinal operation. PMID- 1601917 TI - Juxtarenal abdominal aneurysmectomy. AB - The term juxtarenal abdominal aneurysm is used to describe an aneurysm whose neck is level or adjacent to the origin of one or both renal arteries. Misinterpretation of these appearances could result in the operation being abandoned with the erroneous diagnosis of suprarenal aneurysm. We report 38 patients with a median age of 66 who underwent juxtarenal aneurysm repair, 18 of whom had been diagnosed as having an abdominal aneurysm extending above the renal arteries. Computed tomography, duplex scanning and selective aortography in 7 cases, failed to reveal the true nature of the aneurysm owing to the upper part of the sac lying over the origin of the renal arteries, resulting in aortic tortuosity at this point. The true extent of the aneurysm was best demonstrated by aortography performed in the lateral position. The operations were undertaken through a long midline incision. The aorta is cross-clamped at the supra-renal level and the proximal anastomosis is performed from inside the aneurysm at the level of the renal arteries. The occluding clamp is subsequently re-positioned over the graft ensuring restoration of renal flow and the distal anastomosis is completed in a routine manner. Associated renal artery disease in three hypertensive patients was simultaneously reconstructed. Unfavourable anatomical conditions led to re-implantation of the renal artery in one case and transection with interposition of a vein graft in another. 95% of the patients survived to leave hospital. PMID- 1601918 TI - Parietal inflammatory infiltrate in peripheral aneurysms of atherosclerotic origin. AB - Clinical and histological analyses were made of 18 consecutive cases of peripheral artery atherosclerotic aneurysms (PAAA) (common, deep femoral and popliteal arteries) and compared to a group of 10 specimens obtained from the atherosclerotic, non aneurysmal femoral arteries of 10 cadavers with similar characteristics to the 18 patients. Although neither the clinical nor the macroscopic morphological data indicated the presence of an inflammatory process in the PAAA, the histological examination revealed the presence of a considerable infiltrate (greater than 11 inflammatory cells/2116 microns2) in a surprisingly high percentage of cases (4 cases, 22.8%). In 5 other cases (27.7%) the presence of lymphomonoplasmonocytic cells, although less pronounced, was greater than normally seen in atherosclerotic arterial walls (greater than 4 and less than 11 inflammatory cells/2116 microns2). The median number of inflammatory cells present in the media and adventitia varied from 2.2 +/- 0.3 to 13.2 +/- 0.3 per 2116 microns2. These values are significantly different compared to the results of atherosclerotic arteries at the same level (P less than 0.001 Mann-Whitney's U test). These findings of lymphomonoplasmocytic infiltrates in the absence of other pathology, together with an analysis of the data in the literature, makes it possible to presume that the inflammation present is associated with atherosclerosis and is more common in aneurysmal rather than stenotic forms. The pathogenesis may be determined by immune reaction phenomena. PMID- 1601919 TI - The impact of angiodynography on infrainguinal bypass graft surveillance. AB - We have followed 64 lower extremity in situ grafts and 56 selected vein or prosthetic grafts with serial angiodynography since 1988 (Quantum Color-flow Duplex) and ankle/brachial indices (ABI). Each graft can be scanned in 20 minutes. Scan results affected clinical decision making in 26 cases. There were ten graft stenoses, 10 distal stenoses, 5 large arteriovenous fistulas (AFV), and one limb with a stenosis and AFV. Four other limbs had incompressible vessels and normal angiodynograms. There were no false positives. Twenty-eight graft revisions were performed in 24 patients. Seven stenoses detected by angiodynogram were not accompanied by changes in ABI. Cumulative patency of revised grafts were 61% at 3 years. The detection of graft or distal arterial stenoses by color flow changes is accurate and rapid. Scanning is recommended for all lower extremity bypass grafts. ABI alone is not sufficient. Scanning helps in planning the surgical incision and may obviate arteriography in selected cases. PMID- 1601920 TI - Limb salvage surgery in end stage renal disease: is it worthwhile? AB - The role of limb salvage surgery in patients with end stage renal disease (ESRD) is controversial. In view of this debate, we reviewed our experience with 54 primary and 15 secondary revascularizations for limb salvage in patients with ESRD over the past decade. Thirty-seven patients required dialysis and 10 had functioning renal transplants. Severe limb threatening ischemia was the indication for all revascularizations. The 2-year cumulative secondary graft patency rate was 56.2% with an associated limb salvage rate of 71.4%. There was no significant difference in graft patency or limb salvage rates between patients requiring dialysis and those with functioning renal allografts (p = 0.5). The 30 day operative mortality for the 99 surgical procedures (69 arterial bypasses and 30 additional operations) was 13% and the 2-year patient survival was 45.6%. Six of the 15 amputations were performed despite a patent graft on limbs which had extensive infection and gangrene. We conclude that limb salvage surgery should only be undertaken with recognition of these risks in patients with ESRD or functioning renal transplants. Surgery should be performed before gangrene and infection become extensive. Patients with unrelenting infection or mid-forefoot gangrene should be considered for primary amputation. PMID- 1601921 TI - Management strategy of vascular injuries associated with pelvic fractures. AB - To establish the frequency of major vascular trauma, facilitate recognition of potential injury based on fracture pattern, and formulate a systematic approach to evaluation and management, we studied 429 consecutive patients with acute blunt pelvic fracture. Fracture patterns were grouped as non-ring brakes (n = 43), anterior pelvic ring (n = 197), posterior pelvic ring (n = 104), or acetabular (n = 85) involvement. Mean age was 31 (range 2 to 90); 55% were male. Injuries resulted primarily from motor vehicle accidents (31%), pedestrian injuries (26%), and motorcycle accidents (19%). The fracture pattern was correlated with the occurrence of documented vascular injury, modality of management, transfusion greater than or equal to 10 units in the first day, associated injuries, and outcome. Laparotomy was performed in 22 patients (5%), but helpful only if associated visceral injuries were encountered. There were no instances of iliac or femoral vascular injuries. Hemodynamically unstable patients (BP less than 90) with major pelvic fractures and no other documented source of bleeding underwent pelvic angiography. Posterior ring disruption was associated with vascular injury requiring intervention (p less than 0.001). The occurrence of associated injuries (p less than 0.001), need of greater than 10 units of blood transfusion in the first 24 hours (p less than 0.005), and death (p less than 0.01) were consequences of posterior ring disruption. Based on this experience we conclude that: (1) aortoiliac and femoral arterial as well as iliofemoral venous injuries are a very rare consequence of pelvic fracture; (2) pelvic fracture with posterior ring disruption has a higher incidence of vascular injury necessitating intervention, associated injury, major transfusion requirement, and death; (3) early interventional radiology is efficacious in the control of arterial disruption caused by pelvic fracture; and (4) a tailored management strategy using the expertise of the vascular and orthopedic surgeon as well as the radiologist is required for recalcitrant hemorrhage. PMID- 1601922 TI - Development and long-term fate of a cellular lining in fibrous polyurethane vascular prostheses implanted in the dog carotid and femoral artery. A scanning and light microscopical study up to 53 months after implantation. AB - The development and long-term fate of the inner cellular lining in 72 small caliber (3 mm inner diameter) fibrous polyurethane vascular prostheses explanted from dog carotid and/or femoral arteries at times ranging from 1.5 weeks up to 53 months after implantation were studied by scanning electron and light microscopy. A continuous cellular ingrowth from the vascular stumps into the 3 cm long prostheses was observed, which eventually resulted in a complete cellular lining 6 months after implantation. No other ways of endothelialization were noted. In fully endothelialized prostheses, the cellular ingrowth extended approximately 8 mm into the prostheses and consisted of several layers of fibroblasts and smooth muscle cells, covered by a very thin endothelioid cell layer. The newly developed lining was firmly anchored onto the inner prosthetic surface by means of cellular protrusions extended into the fibrous texture of the prosthetic wall. It was concluded that under experimental conditions in the dog complete endothelialization can be obtained in fibrous polyurethane vascular prostheses and that the lining remained thin and stable throughout the observation period of 53 months after implantation. PMID- 1601923 TI - Thermal laser arterial injury and prostacyclin administration in dogs: thrombotic and hyperplastic consequences. AB - Angioplasty is considered as an alternative to surgical reconstruction of arteriosclerotic vessels especially since lasers and atherectomy devices have become clinically available. However, the resulting arterial injury may lead to acute thrombotic occlusion and chronic restenosis because of hyperplastic vascular repair. The purpose of this experimental study was to evaluate the consequences of thermal laser arterial injury on platelet deposition and myointimal hyperplasia in dog femoral arteries. An intraarterial, short-term prostacyclin (PGI2) infusion was given to evaluate the antithrombotic and antiproliferative effects of this drug. Severe arterial necrosis, partly carbonized and vacuolized, extending to the adventitia was induced by a transluminal heated laser probe motion. The platelet deposition after one hour was 33.62 +/- 6.56 (x 10(6)/cm2.) (mean +/- SEM) without prostacyclin, after 40 ng/kg/min prostacyclin (PGI2) 24.70 +/- 5.45 and after 400 ng/kg/min 9.3 +/- 2.26 (p less than 0.005 no PGI2 vs 400 ng/kg/min PGI2). Myointimal hyperplasia was present eight weeks after thermal laser vascular injury independent of the initially administered prostacyclin. In conclusion, acutely thrombotic and chronically hyperplastic femoral arteries were found following transluminal thermal arterial injury in dogs. Prostacyclin administration could be clinically beneficial in reducing acute vascular thrombosis following thermal angioplasty. Short-term use of this substance, however, may not prevent a hyperplastic response to angioplasty. PMID- 1601924 TI - Traumatic aneurysms of the internal carotid artery at the base of the skull. Two cases treated surgically. AB - Internal carotid aneurysms at the base of the skull after blunt trauma are infrequent but their management is difficult, leading many surgeons to only attempt ligation. We report 2 cases presenting with high traumatic aneurysms, following motorcycle accidents. The 2 aneurysms underwent repair by a venous graft. The petrous portion of the carotid artery was approached and controlled by an ENT surgeon. This "infratemporal" approach was used exposing the facial nerve, combined with temporary anterior sub-luxation of the temporomaxillary joint to expose the lower part of the carotid canal which was opened up with a drill in order to control the carotid artery in the petrous canal. Both patients developed facial nerve palsies which improved within 3 months. Postoperative angiography showed patent vein grafts and the patients were doing well, without any symptoms 18 and 24 months later. PMID- 1601925 TI - Repair of internal carotid aneurysm under local anaesthesia. Case report. AB - Aneurysms of the extracranial carotid arteries are unusual events but cause death or a cerebrovascular accident in the majority of cases (50-70%). This report describes a true internal carotid artery aneurysm that developed within six weeks. The aneurysm was resected and the artery repaired by the use of a graft from the internal jugular vein. Carotid cross-clamping time was 93 minutes. The operation was performed under local anaesthesia, with continuous clinical monitoring of the ipsilateral cerebral hemisphere function. PMID- 1601926 TI - Severe facial ischaemia caused by ergotism. AB - A case of ergotamine induced severe face ischaemia mimicking acute arteritis is presented. The unique clinical picture was due to bilateral involvement of both external carotid arteries. No case of ergotism with such a localization has been previously described in the literature. PMID- 1601927 TI - [Spontaneous rupture of a mucinous cystadenoma of the pancreas and suppuration in the abdomen]. AB - The spontaneous rupture and the suppuration of a mucinous cystadenoma of the pancreas remain exceptional. The authors report about one case. The help provided by ultrasound and computed tomography for the diagnosis is indisputable. The condition is most often mistaken with a pseudocyst of the pancreas. This case is used as a basis to study the mechanism of suppuration and discuss the merits of an emergent histological diagnosis to choose an appropriate therapy. PMID- 1601928 TI - [Skin expansion. A new weapon in the therapeutic arsenal of plastic surgeons]. AB - Skin expansion is a revolutionary technique for plastic surgery. Its principle is based on the observation of clinical facts, such as pregnancy, in which the skin can readily become distended. The technique consists in implanting a silicon prosthesis, connected to a filling valve through a tube, under the skin. The inflation of this prosthesis takes 3 months. At the end of this time, good quality skin with the same features as normal skin (color, hairs, sensation) is available. There are many indications for this technique, including substance losses, removal of congenital tumors and of scars, breast reconstruction or scalp surgery. PMID- 1601929 TI - [Is enterolithiasis a disease occurring more frequently in desert climate? Apropos of 8 cases]. AB - This work is a report about 8 cases of enterolithiasis treated in our University Hospital between 1980 and 1990. We emphasize the rarity of this condition. We also note its relative frequency (5 of 8 cases) in the Bedouin population of our mostly desertic area, and question the possible impact of a diet rich in goat's milk and/or of tuberculosis, which is still endemic in some tribes. We then discuss the difficulties of diagnosis and the essential contribution of small bowel radiographs. The etiologies of enterolithiasis are reviewed, as well as the various modalities of treatment. PMID- 1601930 TI - [Apparently primary site of a melanosarcoma in the small intestine. Apropos of a case]. PMID- 1601931 TI - [Sigmoido-uterine fistula of diverticular origin]. PMID- 1601932 TI - [Another failure in the attempt of definition of the indications to the resection of liver metastases of colorectal origin]. AB - Many discordances can be found in the literature of the last ten years, about the definition of the main prognostic factors after resection of LM from colorectal cancers. Indications of liver resections depend on these prognostic factors. We prospectively enregistred the parameters of 97 patients which had undergone 119 hepatectomies from 1983 to 1990, and we have done a prognostic study. The mean number of resected LM was 2.3, nineteen patients had at least four LM, 22 patients had extrahepatic localization, and 16 had a 0-1 mm free margin. Only one patient died during the postoperative course. The overall five years survival was 33 +/- 8% and the disease free survival was 26 +/- 7%. Unfortunately none prognostic factor significantly influenced the survey in this series, and notably nor the staging of the primitive tumor, nor the synchronous or metachronous happening, nor the number of LM, nor the extrahepatic localizations, nor the free margin. We conclude that: 1) a greater number of patients and a more important follow-up could permit to define clinical or paraclinical prognosis factors but they will be only secondary prognosis factors; 2) it is necessary to prospectively study some new biologic, histologic and immunologic parameters in order to discover the fundamental prognosis factors. PMID- 1601933 TI - [Adrenal gland pheochromocytomas. Apropos of 35 operated patients]. AB - Thirty-five patients (20 female and 15 male, mean age = 47 years) operated on for an adrenal pheochromocytoma were reviewed. Catecholamine excessive production was symptomatic in 33 patients (94%). Urinary excretion of vanyl-mandelic acid, catecholamines and metanephrine was abnormal in 84%, 75% and 90% of cases, respectively. Tumor was presumed benign (no metastasis) in 31 cases. Sensitivity of CT scan (n = 35) and magnetic resonance imaging (n = 13) was 100%. Meta-iodo benzylguanidine scan (n = 19) always recognized the main tumor, but did not visualize 1 second tumor in 1 patient and 1 metastasis in 1 other patient. An anterior intraperitoneal approach was performed in all cases. Operative mortality rate was 5.7%. In the last 15 patients, systematic preoperative treatment by prazosine did not lead to fall in rates of peroperative arrythmia and hemodynamic disorders. Twenty-two of 25 (88%) hypertensive patients remained normotensive without medication postoperatively. The risk of undiagnosed pheochromocytoma and problems in resection of large right-sided tumors are discussed. PMID- 1601934 TI - [Jejuno-ileal diverticula (Meckel excluded). Apropos of 10 cases]. AB - The authors report ten cases of small bowel diverticulosis revealed by a complication in four cases. Aetiologic, pathological, clinical and therapeutic characteristics of this rare disease are reviewed. Main complications are perforations, intestinal obstruction and hemorrhage. The treatment was the resection of the segment of small intestine involved by complicated diverticula. Resection was followed by anastomosis or temporary enterostomy if there was an acute peritonitis. Uncomplicated diverticulae must be respected and left in place. PMID- 1601935 TI - [Lymphangioma of the mesentery. A rare cause of acute abdominal pain syndrome in adults]. AB - We report about one case of cystic lymphangioma of the jejunum in a 27-year-old woman admitted to hospital for abdominal pain. The study of this case and the review of the literature enabled us to bring out the main characteristics of the lesion: rarity in adults, benignancy, mode of occurrence--most often painful--, radiological--and particularly CT--features, diagnosis based on histological findings only, and lastly, treatment with surgical exeresis that must be complete to prevent recurrence. PMID- 1601936 TI - [Asymptomatic giant thoracic dumbbell neurinoma. Apropos of a case]. AB - Giant thoracic dumbbell neurinomas are usually revealed by neurological or mediastinal signs. The case we are reporting was discovered accidentally and allow us to add some accuracy to the current diagnostic criteria for these tumors. MRI provides the most interesting information. The surgical exeresis of these tumors must use a double approach: first laminectomy then thoracotomy. PMID- 1601937 TI - [Abdominal injuries in children. Diagnosis and treatment of renal lesions. Apropos of 26 cases]. AB - During the past ten years, we have treated 26 children with closed renal injuries. Hematuria appeared in 19 cases, but was not detected in 7 other cases, 6 of which corresponded to severe, especially pedicular, lesions. The diagnostic means for the lesion included IVP in 24 cases, ultrasonography in 23, angiography in 8 and computed tomography in 7. The treatment was medical for 18 children and surgical for 8. Observation revealed 4 cases of renal atrophy, including 1 of general atrophy without residual arterial hypertension. On the basis of this series and of a review of the literature, we study the evolution of the diagnosis and treatment of this condition with the development of new medical imaging techniques, especially of CT. PMID- 1601938 TI - [In situ carcinoma and condylomata acuminata of the anus. A plea for an exclusive surgical treatment]. AB - Although the association of in situ carcinoma and pointed condylomas of the anus is unfrequent, their etiopathogenetic similarities require the same diagnostic and therapeutic procedures. The treatment is based on surgical exeresis, the only technique that provides reliable histological findings, ensures healing and does not interfere with subsequent surveillance. PMID- 1601939 TI - [Closed trauma of the tendon of the brachial triceps. Review of the literature. Apropos of 2 cases]. AB - Triceps tendon closed trauma remains a rare injury. A palpable gap with impossible elbow extension against gravity is an important physical finding, and a positive "flake sign" or small avulsion fracture from the olecranon is found in the majority of patients. Trans-osseous suture gives excellent results. Partial lesions must be treated conservatively. PMID- 1601940 TI - Child health promotion, screening and surveillance. AB - After the Second World War, as the incidence of infectious and nutritional disorders declined, professionals and parents began to seek more precise diagnosis and more effective therapy for children with cerebral palsy, mental handicap and related disorders. Although a handful of exceptional men and women had shown what could be accomplished (Shonkoff & Meisels, 1990), the prevailing view was that little could be done and indeed parents of these children were not infrequently advised to "put them in an institution". In the 1950s and 60s, new ideas began to create a more optimistic climate of opinion. It was thought that much, perhaps most, disability was caused by perinatal complications and was therefore potentially preventable; and that early intervention (e.g. physiotherapy for cerebral palsy) might lead to cure or at least substantial improvement. Research in child psychology offered a more scientific basis for the assessment and management of developmental disorders. A sense of urgency was created by the prevalent belief that the child's developing nervous system and psychological functioning were far more amenable to intervention in the first few months or years of life than subsequently (Anastasiow, 1990), and that if suitable therapy was not provided then, the opportunity would be lost for ever. This notion of a "critical period" in development, together with optimism regarding the possibility of intervention, led to a sense of urgency which was responsible for a gradual change in the provision of child health services. Previously, the paediatric health professional had simply waited for the parent to seek advice--the "passive" or "reactive" approach.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1601941 TI - An observational study of the affective concomitants of mastery in infants. AB - The hypothesis that attempts at motor mastery were accompanied by positive affective responses was tested in an observational study of 9-11-month old infants in a daycare setting. Five infants were observed as they attempted three age-appropriate motor tasks--pulling to stand, standing with support, and taking steps with support. Positive affective responses included smiling, babbling, and laughing. The five infants were observed for a total of 82 hours. The proportion of positive affective behaviors associated with practicing new motor tasks was compared to the proportion associated with well-practiced tasks. The hypothesis that more positive affective behaviors would be associated with attempts at mastering the new motor tasks was confirmed. There was no diminution in the association between the new motor tasks and positive affect as the infants continued to practice and master the three motor tasks. The results are discussed in terms of individual differences in mastery motivation and the often suggested continuity between early mastery motivation and later competencies. PMID- 1601942 TI - Young children's views about conflict with peers: a comparison of the daughters and sons of depressed and well women. AB - Forty five-year-olds were interviewed about conflict with peers, based on a simulated dispute between two glove puppets. Recommendations about tactics to be used in resolving conflicts were affected by the child's gender and experience of being cared for by a depressed mother. In particular, the daughters of depressed women were less likely than other children to recommend aggressive solutions to peer conflict; in contrast, the sons of depressed women were more likely than others to advocate aggression. Girls in general recommended more socialized tactics than boys did. PMID- 1601943 TI - The effects of a social support group on depression, maternal attitudes and behavior in new mothers. AB - The present study examined the effects of a postpartum Social Support Group intervention on mood state, attitudes and behavior of new mothers. Intervention conditions consisted of an eight session Social Support intervention (n = 44), a no intervention condition (n = 83) and a Group-by-Mail intervention (n = 15). Attitudinal and behavioral assessments were made before and after the interventions at 6 and 20 weeks postpartum, respectively. The primary results indicate that regardless of intervention condition mothers undergo an improvement in mood from 2 weeks to 5 months postpartum. Although the Social Support intervention did not alleviate maternal depression and, in fact, may be detrimental to depressed mothers' self-confidence, it did increase mothers' proximal attention to their infants. PMID- 1601944 TI - Family stress and functioning in children: the moderating effects of children's beliefs about their control over parental conflict. AB - While factors such as gender and SES have been studied as moderators of stress for children, their perceptions of control have received little attention. In the current study, children's domain-specific perceptions of their control during marital conflict were investigated as potential moderators of the impact of family stress on children's behavior problems, and perceptions of competence. Ninety-four children aged 6-12 years and mothers from families ranging in level of parental conflict from nondiscordant to discordant to physically violent were interviewed. Multiple regression analyses revealed that higher levels of conflict control beliefs acted as compensatory moderators of stress, being associated with lower levels of problem behaviors across stress levels. However, higher conflict control beliefs acted as vulnerability moderators with regard to children's perceptions of competence. PMID- 1601945 TI - Prediction of children's referral to mental health and special education services from earlier adjustment. AB - The 4-year stability in problem behaviors assessed with the Child Behavior Checklist (CBCL), and their predictive validity with regard to poor outcome variables was studied in 1052 4-12-year old children from a general population sample. Irrespective of sex and age, the scores on the CBCL of some 44% of the children remained above the 90th percentile over the 4-year time interval. Externalizing problem behavior tended to show somewhat greater stability than internalizing problem behavior. High initial levels of both internalizing and externalizing problems, and persistence of problems were predictive of referral to mental health services. Referral to special education was higher for younger boys with high initial attention problems and school problems. Police contacts occurred more often in older boys with high initial aggression scores. PMID- 1601946 TI - Abnormal psychosocial situations and ICD-10 diagnoses in children and adolescents attending a psychiatric service. AB - Two recent WHO drafts for ICD-10 diagnoses and the assessment of abnormal psychosocial situations were used in a large cohort of patients attending a child and adolescent psychiatric service. In addition to revealing frequency distributions of psychosocial features, it was shown that a total score of abnormal psychosocial features was mainly dependent on socioeconomic status and was to a lesser extent dependent on age. Sex was not found to be significant. In addition, there was a significant association between IQ and some main categories of the list of psychosocial features. Among diagnoses, the strongest correlations with psychosocial conditions exist for conduct disorders and mixed disorders of conduct and emotions. A high symptom load is associated with higher frequencies of abnormal psychosocial situations. PMID- 1601947 TI - Reliability of a handedness performance test in right and left handed children: a research note. AB - A 25-item handedness performance test was administered twice, at a one-month interval, to 85 elementary school children (60 right handers and 25 left handers in two different age groups). The laterality quotient distribution for right handers was more skewed and significantly different in central tendency and shape than the left handers' distribution. Mean point-biserial item-test correlation was 0.85. The test-retest correlation coefficient for the whole group was 0.79. PMID- 1601948 TI - Psychosocial adjustment in siblings of children with chronic life-threatening illness: a research note. AB - The psychosocial functioning of 10 siblings of children with chronic life threatening illness and their parents was compared with 10 healthy matched controls. The main differences found were in family relationships, with the index siblings expressing more negative emotion in relation to their fathers than controls, index mothers being less involved in social activities and index fathers being less involved with the extended family. No significant differences were found in any of the measures of depression, anxiety and self concept. Index siblings expressed a number of other concerns such as a fear of the break up of their family after the sick child died. The need for increased awareness of the welfare of healthy siblings as well as closer involvement of the fathers is discussed. PMID- 1601949 TI - Psychological adjustment of Yoruba adolescents as influenced by family type: a research note. AB - This research examines the influence of family type on the psychological adjustment of Yoruba adolescents. Using a sample of 116 adolescents, 69 males and 47 females, with mean age of 17.8 years of age (S.D. = 1.72), the results reveal that male adolescents from monogamous families experience better psychological adjustment than their polygynous counterparts, whereas no such difference exists in the levels of psychological adjustment of female adolescents from both family types. These findings suggest that (i) sex-role prescription influences psychological adjustment of adolescents in Yoruba societies, and (ii) female children enjoy more protective upbringing in polygynous families than their male counterparts. PMID- 1601950 TI - Routine screening and quantitation of urinary corticosteroids using bench-top gas chromatography-mass-selective detection. AB - A method was developed for the routine screening, confirmation and quantitation of corticosteroids in human urine using bench top capillary gas chromatography (GC)-mass-selective detection. The free and conjugated corticosteroid fractions were isolated by liquid-liquid partition. After evaporation to dryness under vacuum the corticosteroid residues were derivatized to form the methyloxime trimethylsilyl ether derivatives. Both GC retention data and characteristic spectral data based on authentic reference standards were used for the identification and quantitation of cortisol, cortisone, tetrahydrocortisol and tetrahydrocortisone in the ppb (ng/ml) concentration range. The method is simpler and more efficient than the other GC-mass spectrometric (MS) techniques. It is also more sensitive than the liquid chromatographic-MS method. PMID- 1601951 TI - Liquid membrane work-up of blood plasma samples applied to gas chromatographic determination of aliphatic amines. AB - A technique for sample work-up and enrichment using a supported liquid membrane in an automated flow system, connected to a gas chromatograph, was used for the determination of aliphatic amines in human blood plasma. The amines studied were N,N-dimethylethylamine, triethylamine, N-methylmorpholine, cyclohexylamine and N,N-dimethylcyclohexylamine. An efficient clean-up of the complex plasma matrix was achieved, resulting in identical blank chromatograms for plasma samples and aqueous solutions. Different parameters influencing the efficiency and selectivity of the extraction procedure were experimentally studied and theoretically explained. The detection limit depends on the extraction flow-rate and the available sample volume. With 1 ml of sample and a flow-rate giving an extraction time of 16 min, the detection limit was ca. 5 ppb (5 micrograms/l); with 4 ml of sample and a lower flow-rate, sub-ppb detection limits could be reached in ca. 3 h. Linear calibration curves up to 500 ppb were obtained. Blood plasma samples from volunteers exposed to N,N-dimethylethylamine in air were analysed, and the results compared favourably with independent measurements by another method. PMID- 1601952 TI - Effect of glycation on the heterogeneity of human serum albumin analysed by reversed-phase high-performance liquid chromatography in a solvent containing formic acid. AB - Non-enzymic glycation of human serum albumin (HSA) induces a change in its charge heterogeneity that may account for its particular renal clearance in patients with early diabetic nephropathy. A new high-performance liquid chromatographic analysis for the study of HSA heterogeneity is described based on a high content of formic acid in the mobile phase combined with a concave gradient of isopropanol. Under these conditions, native HSA was separated into three individual components (I, II and III). When glycated HSA was analysed, it was found that although the present method is not suitable for the separation of glycated from non-glycated HSA, it shows the effect of glycation in producing changes in HSA heterogeneity that are different from those reported on surface change. This finding suggests an additional factor (probably conformational changes) that is contributing to the heterogeneity of glycated HSA. PMID- 1601953 TI - Application of solid-phase extraction on anion-exchange cartridges to quantify 5' nucleotidase activity. AB - The enzyme 5'-nucleotidase (5'-ribonucleotide phosphohydrolase, EC 3.1.3.5) catalyzes a critical reaction in intermediary metabolism, the phosphohydrolysis of nucleoside 5'-monophosphates to their corresponding nucleosides. We have evaluated solid-phase extraction on pre-packed anion-exchange cartridges as a chromatographic technique with which 5'-nucleotidase activity may be detected and quantified. Chromatographic conditions were established whereby substrate nucleotide was rapidly and completely separated from its corresponding nucleoside by solid-phase extraction. Both analytes were recovered quantitatively, without loss or degradation. This chromatographic system was integrated into a discontinuous radiochemical assay for 5'-nucleotidase which enabled both substrate utilization and product formation to be assessed simultaneously. Enzyme reaction samples could be analyzed directly for 5'-nucleotidase activity without any pre-chromatography preparation. The high capacity of the solid-phase cartridges and the inability of 5'-nucleotidase to enter the packing bed during analyte elution facilitated termination of the enzyme reaction by applying the entire reaction mixture to the cartridge. Loaded cartridges could then be stored at 4 degrees C prior to chromatography and subsequently batch-eluted. The excellent resolution between substrate and product in solid-phase extraction and the sensitivity of radioisotopic counting enabled detection/quantification of low tissue levels of 5'-nucleotidase in conjunction with ancillary assays for secondary enzyme reactions with the potential to elicit the artifactual loss of 5'-nucleotidase substrate/product when crude biological preparations are examined for 5'-nucleotidase activity. Our results demonstrate that solid-phase extraction on anion-exchange cartridges with elution solvents of appropriate pH offers several unique advantages for 5'-nucleotidase determination. PMID- 1601954 TI - Identification of alpha- and beta-species of calcitonin gene-related peptide in the rat amygdala after separation with capillary zone electrophoresis. AB - Calcitonin gene-related peptide (CGRP) may be present in two forms in nervous tissue. Reversed-phase high-performance liquid chromatography has previously been found to be insufficient to clearly separate alpha-CGRP and beta-CGRP. A method for the separation of CGRPs by capillary zone electrophoresis has been developed. Separation of human or rat alpha-CGRP and beta-CGRP was achieved at pH values between 3.5 and 4.5 and a potential of 20 kV in a fused-silica capillary. Electrophoresis of an extract of rat amygdala in a micropreparative way, with subsequent radioimmunoassay, revealed for the first time the presence of alpha CGRP and beta-CGRP in this brain area. The method may thus be used for separation of CGRPs, to reveal the distribution of alpha-CGRP and beta-CGRP, and for purity control. PMID- 1601955 TI - Determination of hydrazine in biofluids by capillary gas chromatography with nitrogen-sensitive or mass spectrometric detection. AB - Plasma and liver levels of hydrazine were determined at 10, 30, 90 and 270 min in rats given 0.09, 0.27, 0.84 and 2.53 mmol of hydrazine per kg body weight orally by capillary gas chromatography-mass spectrometry of its pentafluorobenzaldehyde adduct (DFBA, m/z 388) using selected ion monitoring with 15N2-labelled hydrazine as the internal standard (adduct, m/z 390). The mean half-life for hydrazine in the plasma was approximately 2 h but varied with dose. Urinary excretion (0-24 h) of hydrazine and its metabolite acetylhydrazine were determined employing nitrogen-phosphorus detection of the adducts utilising a novel internal standard, pentafluorophenylhydrazine, the adduct of which structurally resembles DFBA. The fraction of the original dose excreted as hydrazine (and acetylhydrazine) declined with increasing dose. PMID- 1601956 TI - Simultaneous determination of mexiletine and four hydroxylated metabolites in human serum by high-performance liquid chromatography and its application to pharmacokinetic studies. AB - A high-performance liquid chromatographic method has been developed for the simultaneous determination of mexiletine and its four hydroxylated metabolites in human serum. The method involves a single-step extraction of mexiletine, hydroxymethylmexiletine, p-hydroxymexiletine and their corresponding alcohols with diisopropyl ether-dichloromethane-propan-2-ol (2.5:1.5:0.5, v/v). Separation of the compounds on a deactivated Supelcosil LC8-DB column is accomplished by high-performance liquid chromatography with ultraviolet detection at 203 nm. Overall the recovery of each compound is reproducible and greater than 75%. The lower limit of detection is 2 ng/ml for mexiletine and its metabolites. The application of the method is shown by measuring the concentrations in serum of mexiletine and its metabolites over 24 h in a healthy volunteer after a single intravenous injection of the drug and by monitoring serum concentrations in patients receiving long-term treatment by mouth of the drug. PMID- 1601957 TI - Determination of hydroxychloroquine and its major metabolites in plasma using sequential achiral-chiral high-performance liquid chromatography. AB - A sequential achiral-chiral high-performance liquid chromatographic system has been developed for the determination of the enantiomers of hydroxychloroquine, (+)-HCQ and (-)-HCQ, and the enantiomers of its three major metabolites, bisdesethylchloroquine, desethylhydroxychloroquine and desethylchloroquine, in plasma. The HCQ was separated from the metabolites and interfering components in the plasma and quantified on a cyano-bonded phase, and the enantiomeric composition determined using a Chiral-AGP chiral stationary phase. The assay was validated and applied to the analysis of a pilot study of the pharmacokinetics of (+)- and (-)-HCQ in rabbits. PMID- 1601958 TI - Enantioselective determination of R- and S-(alpha-bromoisovaleryl)urea in plasma using high-performance liquid chromatography after solid-phase extraction. AB - A stereoselective method has been developed for the determination of R- and S (alpha-bromoisovaleryl)urea in plasma and saliva after oral administration. The chiral separation was carried out on Chiralcel OJ or OD columns with hexane--2 propanol as the mobile phase. The poor detection properties of the analyte required the development of an effective sample pretreatment procedure to enable ultraviolet detection at 210 nm. Solid-phase extraction using hydrophobic Amberlite XAD-2 in combination with washing steps at alkaline and acidic pH completely removed interfering components of the biological matrix and allowed the detection of the optical isomers at concentrations down to 10 ng/ml (0.05 microM). The method was validated by determining the recovery, linearity, accuracy and within-day and between-day repeatability at 50, 200 and 2000 ng/ml. Application to the analysis of plasma and saliva samples is demonstrated. PMID- 1601959 TI - Determination of four carboxylic acid metabolites of felodipine in plasma by high performance liquid chromatography. AB - A reversed-phase high-performance liquid chromatography method with ultraviolet detection at 220 nm was developed to determine four carboxylic acid metabolites in plasma following therapeutic doses of the calcium antagonist felodipine. After the addition of an internal standard the analytes were isolated by liquid-liquid and solid-phase extraction. The metabolites were applied to a C2 cartridge in their free acid form, but they were transformed and retained as ion pairs with tetrabutylammonium during a wash with phosphate buffer (pH 7), prior to automated elution and injection by the Varian AASP system onto the analytical C18 column. Using a sample volume of 1 ml of plasma, the lower limit of determination for the metabolites was about 20 nmol/l. The influence of the pH of the mobile phase on the retention time of the metabolites and the structural requirements for the internal standard were studied. The method was applied to plasma samples from four dogs collected after an oral dose of felodipine. The plasma concentration time profiles of the metabolites gave useful information about the mechanisms by which they were formed and eliminated. PMID- 1601960 TI - Determination of heptylphysostigmine in plasma by high-performance liquid chromatography with electrochemical detection. AB - An analytical method was developed with sensitivity to detect clinically significant concentrations of heptylphysostigmine (HP), a new physostigmine derivative with potent and long-lasting inhibitory activity on cholinesterase. HP, an experimental drug for Alzheimer disease, was measured in human plasma by high-performance liquid chromatography with electrochemical detection with use of a normal-phase column and acetonitrile buffer containing tetrahydrofuran and sodium acetate, pH 4.6. The limit of detection of the method was 0.125 ng/ml using a 2-ml sample of plasma. Analytical recovery of HP was 53.04 +/- 7.75% for plasma in the range 0.25-2.5 ng/ml. Stability studies conducted at 37 degrees C indicated that the drug was stable in 1 M hydrochloric acid, 1 M hydrogen peroxide and sodium acetate-buffered solution at pH 4 for at least 6 h but at pH 7 it degraded slightly to 79% at 6 h and was unstable in 1 M sodium hydroxide with only 9% of the parent compound remaining at 30 s. HP was stable when exposed to ultraviolet light at 22 degrees C or 100% relative humidity at 37 degrees C, with almost 80 and 75% of the parent compound remaining after 4 and 28 days, respectively. HP was stable in plasma at 4 degrees C for 0.25 h, and it slowly degraded to 56 and 28% of the original concentration by 1 and 2 h, respectively. HP was highly unstable in plasma at higher temperatures; at 22 and 37 degrees C it degraded immediately to 48 and 36% of the original concentration and was not detected after 0.5 and 0.25 h, respectively. PMID- 1601961 TI - Column-switching high-performance liquid chromatographic detection of pholcodine and its metabolites in urine with fluorescence and electrochemical detection. AB - A sensitive and selective method for the detection of pholcodine and its metabolite morphine in urine using high-performance liquid chromatography is described. It involves on-line clean-up of urine on a trace enrichment column packed with a polymeric strong cation-exchange material. Pholcodine and its metabolites were separated on two analytical columns with different selectivities. Pholcodine was detected by a fluorescence detector and morphine was detected electrochemically. One system, based on reversed-phase chromatography, applied a polystyrene-divinylbenzene column and gradient elution. The other system was based on normal-phase chromatography with a silica column and isocratic elution. Morphine was confirmed to be a metabolite of pholcodine by reversed-phase chromatography and electrochemical detection. Two unidentified metabolites of pholcodine were separated from pholcodine by normal-phase chromatography and detected by fluorescence detection. PMID- 1601962 TI - Determination of ofloxacin in human serum by high-performance liquid chromatography with column switching. AB - The chromatographic behaviour of ofloxacin on various sorbents, including ODS, C8, C1, nitril, phenyl and tert,-butyl, as stationary phases was investigated and a high-performance liquid chromatography (HPLC) assay was developed for the determination of ofloxacin in serum. The serum samples were directly introduced onto an HPLC column after filtering through a Morcut II membrane filter to remove proteins. The filtrate was concentrated on a pre-column using a phenyl stationary phase and was then introduced to an analytical column with an ODS stationary phase by column switching. Ofloxacin and enoxacin as an internal standard were detected by ultraviolet absorbance at 300 nm. Determination was possible for ofloxacin over the concentration range 50-2000 ng/ml; the limit of detection was 20 ng/ml. The recovery of ofloxacin added to serum was 88.8-101.7% with a coefficient of variation of less than 5.2%. This method is applicable to pharmacokinetic studies of patients after treatment with ofloxacin. PMID- 1601963 TI - Simultaneous determination of a novel angiotensin II receptor blocking agent, losartan, and its metabolite in human plasma and urine by high-performance liquid chromatography. AB - A sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of a new angiotensin II receptor blocking agent, losartan (DuP 753, MK-954, I), and its active metabolite, EXP3174 (II), in human plasma or urine is described. The two analytes and internal standard are extracted from plasma and urine at pH 2.5 by liquid-liquid extraction and analyzed on a cyano column with ultraviolet detection at 254 nm. The mobile phase is composed of acetonitrile and phosphate buffer at pH 2.5. The limit of quantification for both compounds in plasma is 5 ng/ml. The limit in urine is 20 and 10 ng/ml for I and II, respectively. The assay described has been successfully applied to samples from pharmacokinetic studies. PMID- 1601964 TI - High-performance liquid chromatographic procedure for specificity testing of radioimmunoassays: rolipram. AB - A high-performance liquid chromatographic (HPLC) procedure for testing the specificity of radioimmunoassays (RIA) was developed using the same method of extraction as in the RIA, followed by fractionation of the extract by HPLC and subsequent measurement of cross-reactions in all the fractions according to the normal RIA procedure. The RIA of rolipram, an antidepressant drug, was checked in plasma samples obtained from pharmacokinetic studies in rats, rabbits, cynomolgus monkeys and humans. The antibody was shown to be specific in the plasma samples from the laboratory animals, but not in human plasma. This was because in human plasma a metabolite occurred with a structure similar to that used for the hapten in the immunization process. This metabolite was not found in the plasma of the animal species investigated. The test procedure described is generally applicable, making the time-consuming development of an alternative method such as gas chromatography-mass spectrometry unnecessary. PMID- 1601965 TI - Identification by high-performance liquid chromatography of tyrosine ammonia lyase activity in purified fractions of Phaseolus vulgaris phenylalanine ammonia lyase. AB - Activities of phenylalanine ammonia-lyase (PAL) and tyrosine ammonia-lyase (TAL) were assessed at each stage of a three-step purification of PAL. Assays were performed by high-performance liquid chromatographic (HPLC) separation and ultraviolet detection of reaction products. Use of HPLC permitted assay of low activities of PAL and TAL for periods up to approximately four and two days, respectively. HPLC also facilitated the accurate quantitation of the product of the TAL reaction, trans-p-coumaric acid, which was observed to isomerize readily under experimental conditions. PAL and TAL were associated throughout the purification procedure, with TAL activity at 0.6-1.3% of PAL activity. It was concluded that, contrary to previous reports, TAL and PAL activities are mediated by the same enzyme, or else by chromatographically very similar enzymes. PMID- 1601966 TI - Electron-capture gas chromatographic procedure for simultaneous determination of amphetamine and N-methylamphetamine. AB - An electron-capture gas chromatographic procedure for the simultaneous determination of amphetamine and N-methylamphetamine in biological samples is described. The method employs extraction with the ion-pairing reagent bis(2 ethylhexyl)phosphoric acid, and back-extraction with 0.5 M hydrochloric acid. The hydrochloric acid phase is basified, and the amphetamines and the internal standard benzylamine are derivatized with pentafluorobenzenesulfonyl chloride prior to analysis on a gas chromatograph equipped with a capillary column. Levels of amphetamine and N-methylamphetamine have been determined in the urine and liver of rats treated chronically with (-)-deprenyl. PMID- 1601967 TI - Simultaneous high-performance liquid chromatographic determination of urinary metabolites of benzene, nitrobenzene, toluene, xylene and styrene. AB - A high-performance liquid chromatographic method is described for the simultaneous determination of six urinary metabolites of several aromatic chemicals: phenol (from benzene), hippuric acid (from toluene), 3-methylhippuric acid (from xylene), mandelic and phenylglyoxylic acid (from styrene) and 4 nitrophenol (from nitrobenzene). Reversed-phase liquid chromatography was performed in an isocratic mode at 1 ml/min on a 5-microns C18 column using two mobile phases: (A) acetonitrile-1% phosphoric acid (10:90); (B) acetonitrile-1% phosphoric acid (30:70). Phase A separates the six metabolites well, but phase B allows to a more rapid and reproducible simultaneous determination of phenolic compounds than phase A. For these compounds a prior enzymic hydrolysis step using Helix pomatia juice is performed to hydrolyse their sulphate and glucuronate conjugates. The reproducibility and the specificity are both excellent. Furthermore, the method is rapid, economical and easily automated. The proposed method appears very suitable for the routine monitoring of workers exposed to these chemicals on the basis of the biological threshold limit values. PMID- 1601968 TI - Determination of apovincaminic acid in serum by means of high-performance liquid chromatography. AB - A high-performance liquid chromatographic method for the determination of low concentrations in serum of apovincaminic acid, the main metabolite of vinpocetine, is reported. The assay includes a two-step ion-pair extraction with tetrabutylammonium as counter ion. Recovery is ca. 40%. Separation is performed on a narrow-range 5 microns particle size octadecylsilane modified silica packing. Heptanesulphonic acid is the pairing ion in the eluent, and the ultraviolet detection wavelength is 224 nm. Yohimbine serves as the internal standard. The assay is fast, accurate and sensitive quantifying at least 5 ng/ml apovincaminic acid in serum. The method was applied to the analysis of serum samples from aged subjects, treated with a 20-mg dose of vinpocetine. PMID- 1601969 TI - Bio-analysis of vinorelbine by high-performance liquid chromatography with fluorescence detection. AB - A simple and selective procedure for the determination of vinorelbine, a new semi synthetic vinca alkaloid, is presented. The method is based on ion-exchange high performance liquid chromatography on normal-phase silica with fluorescence detection, combined with liquid-liquid extraction using diethyl ether for sample clean-up. The absence of endogenous interferences and the excellent chromatographic behaviour of vinca alkaloids provides accurate results even at low concentrations. The limit of determination in plasma is 1.5 micrograms/l (500 microliters sample). Reproducible recoveries in urine were obtained if 10-50 microliters of sample were processed supplemented with 500 microliters of blank plasma. PMID- 1601970 TI - Determination of oxytetracycline in blood serum by high-performance liquid chromatography with direct injection. AB - A direct injection analysis by high-performance liquid chromatography has been developed for oxytetracycline in serum of animals and fish. A Hisep shielded hydrophobic phase column (15 cm x 4.6 mm I.D.) and a mobile phase of methanol-0.2 M oxalic acid (10:90, v/v, pH 7.0) with ultraviolet detection at 360 nm were used. The standard calibration curves in serum of chicken, hog, cattle and rainbow trout were linear over the range 0.1-20 micrograms/ml. The recoveries of oxytetracycline from all serum samples determined at two different concentrations (0.5 and 2.0 micrograms/ml) were 88-103%. The detection limit was 0.05 micrograms/ml for every serum sample. PMID- 1601971 TI - Determination of nadolol in serum by high-performance liquid chromatography with fluorimetric detection. AB - A sensitive high-performance liquid chromatographic method for a routine assay of nadolol in serum is described. Serum samples spiked with atenolol (internal standard) were extracted with diethyl ether. After centrifugation, the organic layer was evaporated to dryness. The residue was redissolved in the mobile phase and injected onto an octadecyl silica column (150 mm x 4.6 mm I.D.). The mobile phase was 0.05 M ammonium acetate (pH 4.5)-acetonitrile (85:15, v/v). Fluorometric detection (excitation 230 nm, emission 300 nm) was used. The minimum detectable level of nadolol in serum was 1 ng/ml. PMID- 1601972 TI - Determination of bisaramil and its metabolite in plasma using high-performance liquid chromatography with electrochemical detection. AB - A column liquid chromatographic method using electrochemical detection has been developed for determination of an antiarrhythmic agent, bisaramil, and its metabolite in plasma. The plasma was fractionated by extraction with chloroform and chloroform-ethanol, and each fraction was dried and dissolved in ethyl acetate. After back-extraction into an acidic buffer, bisaramil was chromatographed on a reversed-phase column, and the metabolite, which has a higher polarity, was analysed by ion-pairing chromatography. Calibration curves were linear over the concentration range 2-200 ng/ml with coefficients of variation, within-day or day-to-day, not exceeding 5% at any level. The limits of detection of bisaramil and its metabolite were 0.5 and 1 ng/ml, respectively, using 0.5 ml of plasma. The dual-electrode detector was operated in the screening mode of oxidation (electrode 1, +0.55 V; electrode 2, +0.8 V), providing a greater specificity and reducing the background noise. This procedure was applied to a large number of samples in a pharmacokinetic study at the therapeutic dose. PMID- 1601973 TI - Application of preparative liquid chromatography to the isolation of enantiomers of a benzodiazepinone derivative. AB - The isolation of milligram amounts of the enantiomers of a benzodiazepinone derivative was performed on an analytical cellulose tribenzoate-based column by multiple repetitive injections. An enantiomeric purity greater than 98% was required. First, an analytical method was developed to maximize the resolution by adjusting the mobile phase composition, flow-rate and most importantly the column temperature. Then the preparative separation was optimized by adjusting the sample size and detecting the sample where its UV absorbance was low. The locations of the cut points were determined by use of detector response levels. The method development, preparative separations and analytical assays of the fractions obtained were all performed on analytical columns. PMID- 1601974 TI - Purification of erucic acid by preparative high-performance liquid chromatography and crystallization. AB - Erucic acid (C22:l fatty acid) has been found to be useful in the treatment of adrenoleukodystrophy (ALD). It appears to work by reducing the blood levels of very-long-chain fatty acids (VLCFAs) which destroy the myelin sheaths of the nerves. Erucic acid was purified by reversed-phase high-performance liquid chromatography (HPLC) on columns packed with YMC C18 (10-20 microns, 120 A). Using ethanol-water as the mobile phase, the recovery of erucic acid was 69% and the purity was more than 97% as measured by gas chromatography. The amount of saturated VLCFAs was found to be within the limits specified for ALD treatment. The production rate (yield per 8 h shift) was low, however. Using methanol-water instead of ethanol-water as the mobile phase, a ninefold increase in the production rate was achieved. The recovery of erucic acid was 65% and the purity of erucic acid was 98%. All other purity specifications were met. By performing a low-temperature crystallization after the preparative HPLC step, the production rate was increased a further 142%. This represents a 22-fold increase in production rate over the ethanol-water method. The crystalline erucic acid was found to be 99% pure. All other purity requirements were met. The yield for the combined process (HPLC plus crystallization) decreased to 55%, however. PMID- 1601975 TI - Preparative high-performance liquid chromatographic separation and isolation of bacitracin components and their relationship to microbiological activity. AB - Bacitracin, a polypeptide antibiotic, is one of the most commonly used antibiotics in the world. The approved method of analysis for bacitracin is microbial. To correlate the microbiological method with a high-performance liquid chromatographic (HPLC) method, bacitracin was chromatographed using HPLC with ultraviolet detection and a YMC basic column. Adequate separation of the isomers was obtained to scale up this procedure to preparative HPLC using a Prep HPLC system and a 250 x 21 mm YMC basic column. The various fractions were separated, isolated and examined for microbial activity. The individual fractions could be precipitated by adding zinc or methylene disalicylic acid and lowering the pH. The crude fractions were recycled to ensure chromatographic purity. The chromatograms can accurately predict (in minutes) the microbiologically determined potency which usually takes 16-24 h to develop. The chromatographic procedure also provides information on the amounts of isomers and degradation products present in the sample, whereas the microbiological assay only provides activities or potencies of the antibiotic. The reported HPLC method also possesses some advantages over some other published HPLC methods in terms of accuracy and time of analysis. PMID- 1601976 TI - Preparative isolation of vitamin D2 from previtamin D2 by recycle high performance liquid chromatography. AB - A preparative high-performance liquid chromatographic method, based on recycle chromatography, to separate vitamin D2 (ergocalciferol) from previtamin D is described. The method provides efficient separation by means of a mixture of methanol, acetonitrile and hexane as eluent on a reversed-phase C18 column. Scale up to a 2-in. diameter column resulted in the collection of 100% pure fractions based on UV detection at 265 nm. The total throughput and the economics of the purification were also optimized. PMID- 1601977 TI - Economic considerations important in the scale-up of an ovalbumin separation from hen egg-white on the anion-exchange cellulose DE92. AB - The scale-up of the separation of hen egg-white proteins has been investigated using Whatman DE92 anion-exchange cellulose. Having developed suitable chromatographic conditions, a maximum binding capacity of 100 mg protein/ml packed DE92 was determined in a 25-ml column. The process was scaled up 1000-fold and the influence of batch and column techniques on the chromatographic step assessed. Data indicate column processes to be more efficient than batch in the adsorptive stage. PMID- 1601978 TI - High-performance membrane chromatography of serum and plasma membrane proteins. AB - Porous discs made of poly(glycidyl methacrylate) were used for high-performance membrane chromatography (HPMC) of proteins. In model experiments, separations of standard proteins by anion-exchange HPMC using a DEAE disc were carried out. The influences of sample distribution and disc diameter and thickness on separation performance were studied. The separation disc allowed a scaling-up from analytical (diameter 10 mm) to semi-preparative (diameter 50 mm) dimensions. In an application study, separations with anion-exchange and affinity HPMC were carried out using different complex samples such as rat serum and plasma membrane proteins. In all experiments the results on poly(glycidyl methacrylate) discs were comparable to those achieved on adequate high-performance liquid chromatographic (HPLC) columns. However, the separations on HPMC discs could be carried out faster than corresponding separations on HPLC columns. The pressure drop on the discs was low even at high flow-rates. The experiments show that the poly(glycidyl methacrylate) discs used are especially suitable for the isolation of proteins and other biopolymers which occur in a diluted state in complex mixtures. PMID- 1601979 TI - Influence of gangliosides on experimental allergic neuritis. AB - The development of myelin-induced experimental allergic neuritis (EAN) in Lewis rats can be depressed and delayed by adding a ganglioside mixture (GM1, GD1a, GD1b, GT1b) to the immunization compound; however, gangliosides may enhance the induction of adjuvant arthritis. Antibodies against multiple gangliosides are produced in rats after immunization with gangliosides after addition of myelin, but only low titers can be detected in animals immunized with myelin and complete Freund's adjuvant alone. We conclude that this antibody production is not the result of peripheral nerve inflammation but depends rather from external applied gangliosides. PMID- 1601980 TI - Interferon-gamma regulation of C3 gene expression in human astroglioma cells. AB - In this report, we show that the human astroglioma cell line, D54-MG, constitutively expresses C3 mRNA and secretes antigenically detectable C3 protein. The cytokine interferon-gamma (IFN-gamma) enhances C3 mRNA and protein expression by D54-MG cells in a dose- and time-dependent manner. C3 mRNA from both D54-MG cells and primary human adult astrocytes has the same apparent size (5.1-5.2 kb) as C3 mRNA from hepatocyte and monocyte cell lines. Constitutive C3 mRNA levels in D54-MG cells and primary human astrocytes are comparable. Primary rat astrocytes also constitutively express C3 mRNA, which is enhanced upon exposure to IFN-gamma. These data are novel since expression of C3 in other cell types is refractory to IFN-gamma. In the central nervous system (CNS), endogenous complement production by astrocytes, and enhancement by the cytokine IFN-gamma, may contribute to the pathogenesis of inflammatory demyelinating diseases such as multiple sclerosis (MS). PMID- 1601981 TI - Mucosal infection with Neisseria gonorrhoeae. Bacterial adaptation and mucosal defenses. PMID- 1601982 TI - Blocking of lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) inhibits murine melanoma lung metastasis. AB - The 90-kD lung endothelial cell adhesion molecule-1 (Lu-ECAM-1) selectively promotes Ca(2+)-dependent adhesion of lung-metastatic B16 melanoma cells. Corresponding with their metastatic performance, high lung-metastatic B16-F10 melanoma cells bind in significantly higher numbers to Lu-ECAM-1 than their intermediate and low lung-metastatic counterparts B16-L8-F10 and B16-F0, respectively. Maximum attachment is observed at a density of approximately 2.4 x 10(2) Lu-ECAM-1 sites/microns2 of plastic surface. B16 melanoma cell binding to Lu-ECAM-1 is blocked by mAb 6D3 and is competitively inhibited by soluble Lu-ECAM 1. C57B1/6 mice passively immunized with anti-Lu-ECAM-1 mAb 6D3 or actively immunized with purified Lu-ECAM-1 exhibit an anti-Lu-ECAM-1 antibody titer dependent reduction in the number of B16 experimental metastases. Lu-ECAM-1 promotes neither binding nor metastasis of other lung-metastatic tumor cells (e.g., KLN205). Our data indicate that an "antiadhesion" therapy directed at interfering with the adherence of blood-borne tumor cells to organ-specific vascular endothelium is efficient in the control of metastasis formation in selective organ sites. PMID- 1601983 TI - Investigation of human giardiasis by karyotype analysis. AB - The patterns of transmission of Giardia lamblia and the potential contribution of strain differences to pathogenicity of infection is poorly understood. We used pulsed field gradient gel electrophoresis (PFGE) to separate chromosome-sized DNA molecules of 22 stocks of G. lamblia isolated from 13 individuals (6 symptomatic, 7 asymptomatic) living in Jerusalem. PGFE gels run under a variety of conditions revealed up to nine ethidium bromide-stained bands per isolate ranging in size from 0.7 to greater than 3 megabasepairs. Relative staining intensities indicated that some bands contained multiple chromosomes. Major differences in the number, size, and intensity of bands allowed a clear differentiation of the karyotypes of isolates from each of the different individuals. This is in contrast to previous studies where the karyotype of different isolates have been strikingly homogeneous. Hybridization of Southern blots with surface antigen, beta-tubulin, and ribosomal RNA genes revealed that these gene families were distributed to different sized chromosomes amongst the different isolates. PFGE thus revealed major differences in the karyotypes of different G. lamblia isolates that were obtained over a short period of time from a relatively confined geographic area. In contrast, karyotypes of isolates established either by direct cultivation of duodenal trophozoites or by excystation of stool cysts from the same individuals were almost identical. Also, isolates from the same individuals obtained over a prolonged period of time revealed only minor differences in their karyotype, suggesting that recurrent infection can be caused by genetically similar organisms. We conclude that chronic giardiasis can result from recurrence of occult infection or reinfection from a common source. PMID- 1601984 TI - Dynamics of the cellular and humoral components of the inflammatory response elicited in skin blisters in humans. AB - Skin blisters induced by suction on the forearm of normal volunteers provide a convenient model to study the inflammatory response in vivo in man. In our study, after removal of the roof of the blister, i.e., the epidermis, the exposed floor of the blister (dermal-epidermal interface) was bathed with 70% autologous serum using a multiwell skin chamber. Migration of leukocytes (90-95% neutrophils) into the chamber fluid was detectable within 3 h, and appeared to plateau at 16-24 h. Sampling of the dermal-epidermal interface revealed primarily mononuclear cells during the first 8 h of the inflammatory response; however, their prevalence at 24 h was greatly diminished due to neutrophil infiltration. Accompanying the cellular immune response was the accumulation of inflammatory mediators in the bathing medium. The accumulation of IFN-gamma reached a plateau within 3 h; significant accumulations of the complement fragment, C5a, and of leukotriene B4 were also detected at 3 h. The accumulation of C5a did not peak until 5 h, whereas leukotriene B4 continued to accumulate through 24 h. IL-6 and IL-8 concentrations were minimal at 3-8 h but dramatic by 24 h while IL-1 beta, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor were undetectable within 3-8 h, but markedly elevated by 24 h. There was little accumulation of IL-4 and no accumulation of IL-1 alpha or IL-2 during the 24-h period. The sequential appearance of mediators at an inflammatory focus suggests that a carefully regulated dynamic system is responsible for controlling the evolution of the inflammatory response. PMID- 1601986 TI - Effects of hemipancreatectomy on pancreatic alpha and beta cell function in healthy human donors. AB - To assess the metabolic consequences of hemipancreatectomy in humans, we determined pancreatic beta and alpha cell function in healthy donors. Donors examined cross-sectionally were found to have significantly decreased glucose induced phasic insulin secretion and arginine-induced insulin and glucagon secretion as compared to age, sex, and body index-matched controls. However, their fasting glucose and insulin values were not different from controls. Similar observations were found in the prospective evaluation of eight donors before and 15 +/- 2 mo after hemipancreatectomy. Beta cell reserve, as measured by glucose potentiation of arginine-induced insulin secretion, was significantly decreased in donors (maximal acute insulin response [AIRmax]: donors = 666 +/- 84 pM vs controls = 1,772 +/- 234 pM) while the PG50 (the glucose value at which the half-maximal response was observed) was the same in the two groups. Donors and controls responded to 60-min continuous intravenous infusions of glucose by reaching identical serum glucose values, despite significantly lower insulin secretory responses in donors. We conclude that hemipancreatectomy in human donors is associated with decreased pancreatic alpha and beta cell function. Since donors generally maintain normoglycemia after hemipancreatectomy despite diminished insulin secretion, our data suggest that healthy humans may compensate for hemipancreatectomy by increasing glucose disposal. PMID- 1601985 TI - Albumin gene expression is down-regulated by albumin or macromolecule infusion in the rat. AB - A novel feedback regulatory mechanism operating on transcription of the albumin gene is described in the rat. In 1946, it was proposed that circulating colloids, including serum albumin, may affect the synthesis and/or secretion of albumin in the liver. The molecular basis for this proposed regulation has now been investigated by adding oncotically active macromolecules to the circulation of normal or genetically albumin-deficient Nagase analbuminemic rats (NAR) and analyzing the hepatic expression of genes, including albumin after 24 h. The transcription rate of the albumin gene was higher in NAR than in normal rats and was dramatically reduced by raising serum albumin to 1.6 g/dl. Intravenous infusion of albumin into normal rats also decreased transcriptional activity of the albumin gene by 50-60%, and this decrease correlated with changes in serum colloid osmotic pressure after albumin infusion. Inhibition of albumin gene transcription was also observed upon intravenous infusion of other protein or nonprotein macromolecules, such as gamma-globulin and dextran. This down regulation appears to control the steady-state level of albumin mRNA in the liver. Aside from a concomitant decrease in apo E gene transcription after albumin or macromolecule infusion, there was no change in the transcription rate of other genes, including those exhibiting liver-preferred or -specific expression (e.g., tyrosine amino-transferase, cytochrome P-450, alpha 1 antitrypsin, apolipoproteins A-I and B, and transferrin) or general cellular expression (e.g., alpha-tubulin, pro alpha 2 collagen, and beta-actin). Feedback regulation of albumin gene expression by serum colloids may serve as a specific homeostatic mechanism to maintain the steady-state level of total protein in the circulation. PMID- 1601987 TI - Glucose-free fatty acid cycle operates in human heart and skeletal muscle in vivo. AB - Positron emission tomography permits noninvasive measurement of regional glucose uptake in vivo in humans. We employed this technique to determine the effect of FFA on glucose uptake in leg, arm, and heart muscles. Six normal men were studied twice under euglycemic hyperinsulinemic (serum insulin approximately 500 pmol/liter) conditions, once during elevation of serum FFA by infusions of heparin and Intralipid (serum FFA 2.0 +/- 0.4 mmol/liter), and once during infusion of saline (serum FFA 0.1 +/- 0.01 mmol/liter). Regional glucose uptake rates were measured using positron emission tomography-derived 18F-fluoro-2-deoxy D-glucose kinetics and the three-compartment model described by Sokoloff (Sokoloff, L., M. Reivich, C. Kennedy, M. C. Des Rosiers, C. S. Patlak, K. D. Pettigrew, O. Sakurada, and M. Shinohara. 1977. J. Neurochem. 28: 897-916). Elevation of plasma FFA decreased whole body glucose uptake by 31 +/- 2% (1,960 +/- 130 vs. 2,860 +/- 250 mumol/min, P less than 0.01, FFA vs. saline study). This decrease was due to inhibition of glucose uptake in the heart by 30 +/- 8% (150 +/- 33 vs. 200 +/- 28 mumol/min, P less than 0.02), and in skeletal muscles; both when measured in femoral (1,594 +/- 261 vs. 2,272 +/- 328 mumol/min, 25 +/- 13%) and arm muscles (1,617 +/- 411 to 2,305 +/- 517 mumol/min, P less than 0.02, 31 +/- 6%). Whole body glucose uptake correlated with glucose uptake in femoral (r = 0.75, P less than 0.005), and arm muscles (r = 0.69, P less than 0.05) but not with glucose uptake in the heart (r = 0.04, NS). These data demonstrate that the glucose-FFA cycle operates in vivo in both heart and skeletal muscles in humans. PMID- 1601988 TI - Human autoantibodies against desmoplakins in paraneoplastic pemphigus. AB - Recently, a previously unrecognized autoantibody mediated blistering disease, paraneoplastic pemphigus has been described. Paraneoplastic pemphigus is associated with lymphoid malignancies, thymomas, and poorly differentiated sarcomas. Serum of affected patients contain pathogenic autoantibodies that immunoprecipitate from normal keratinocytes a characteristic complex of four polypeptides with M(r) of 250, 230, 210, and 190 kD. As our preliminary studies indicated that the 250-kD and the 210-kD antigens comigrated with desmoplakins I and II, we investigated the possibility that autoantibodies against the desmoplakins were a component of this autoimmune syndrome. 11 sera from affected patients were tested by indirect immunofluorescence against desmosome containing tissues, immunoprecipitation of metabolically labeled keratinocytes, and Western immunoblotting of desmoplakins I and II that had been purified to homogeneity from pig tongue epithelium. By indirect immunofluorescence, 9 of 11 sera showed strong binding to epithelial and nonepithelial desmosomes, and 2 were weakly reactive. All 11 immunoprecipitated 250- and 210-kD bands of variable intensity that comigrated with bands identified by a murine monoclonal antidesmoplakin antibody, and immunoblotting confirmed binding of the serum autoantibodies to purified desmoplakins. This demonstrates that paraneoplastic pemphigus is the first human autoimmune syndrome in which autoantibodies against the desmoplakins are a prominent component of the humoral autoimmune response. PMID- 1601989 TI - Polymorphism in the human apolipoprotein A-I gene promoter region. Association of the minor allele with decreased production rate in vivo and promoter activity in vitro. AB - We investigated a common polymorphism in the human apolipoprotein A-I gene promoter at a position 76 bp upstream of the transcriptional start site. 54 human subjects, whose apoAI production rates had been determined by apoAI turnover studies, were genotyped at this polymorphic position by a novel technique using polymerase chain reaction followed by primer extension. 35 subjects were homozygous for a guanosine (G) at this locus and 19 were heterozygous with a guanosine and adenosine (A). The apoAI production rates were significantly lower (by 11%) in the G/A heterozygotes than in the G homozygotes (P = 0.025). In spite of the apparent effect of this apoAI gene promoter polymorphism on the apoAI production rate, there was no effect on HDL cholesterol or apoAI levels. To investigate whether the observed difference in apoAI production rates was related to differential gene expression of the two alleles, promoters containing either allele were linked to the reporter gene chloramphenicol acetyltransferase, and relative promoter efficiencies were determined after transfection into the human HepG2 hepatoma cell line. The A allele expressed only 68% +/- 5% as well as the G allele, a result consistent with the in vivo apoAI production rate data. PMID- 1601990 TI - First-pass gastric mucosal metabolism of ethanol is negligible in the rat. AB - Ethanol metabolism by gastric alcohol dehydrogenase (ADH) is thought to be an important determinant of peripheral ethanol time-concentration curves (AUCs) in rats and humans. We quantitated this metabolism in rats by measuring the gastric absorption of oral ethanol (0.25 g/kg) and the gastric venous-arterial (V-A) difference of ethanol versus ethanol metabolites (acetate, acetaldehyde, and bicarbonate). Over 1 h, approximately 20% of the ethanol was absorbed from the stomach and 70% was emptied into the duodenum. The gastric V-A difference of ethanol metabolites was less than 4% of that of ethanol. Thus, gastric metabolism accounted for less than 1% (less than 4% of 20% absorbed) of the dose. This negligible metabolism was predictable from the low affinity of gastric ADH for ethanol. In contrast, gastric ADH has a high affinity for octanol, and 66% of this compound was metabolized during gastric absorption. Evidence supporting gastric metabolism of ethanol largely derives from the lower AUCs observed after oral than after intravenous administration; however, we observed increasingly higher AUCs with increasingly rapid portal vein infusions of identical ethanol doses. We conclude that gastric metabolism of ethanol is negligible in the rat, and differences in AUCs ascribed to gastric metabolism may reflect differences in ethanol absorption. PMID- 1601991 TI - Retroviral gene transfer to primitive normal and leukemic hematopoietic cells using clinically applicable procedures. AB - Clinical uses of gene transfer to bone marrow transplants require the establishment of a reproducible method for infecting large numbers of very primitive hematopoietic cells at high efficiency using cell-free retrovirus containing media. In this study we report the results of experiments with preparations of a high-titer (2-5 x 10(7)/ml) helper-free recombinant neo(r) retrovirus that indicate this goal can now be achieved based on measurements of gene transfer efficiencies to cells referred to as long-term culture initiating cells (LTC-IC) because they give rise to clonogenic cells after greater than or equal to 5 wk in long-term culture (LTC). Intermittent, repeated exposure of normal human marrow mononuclear cells to virus-containing supernatant over a 3-d period of cell maintenance on an IL-3/granulocyte colony-stimulating factor (G CSF) producing stromal layer resulted in gene transfer efficiencies to LTC-IC of 41%; a level previously obtainable only using co-cultivation infection techniques. Marrow cells enriched greater than or equal to 500-fold for LTC-IC (1 2% pure) by flow cytometry showed gene transfer efficiencies of 27% when infected in a similar fashion over a shorter period (24 h), but in the presence of added soluble IL-3 and G-CSF without stromal feeders, and this increased to 61% when Steel factor was also present during the infection period. By using a less highly enriched population of LTC-IC obtained by a bulk immunoselection technique applicable to large-scale clinical marrow harvests, gene transfer efficiencies to LTC-IC of 40% were achieved and this was increased to 60% by short-term preselection in G418. Southern analysis of DNA from the nonadherent cells produced by these LTC over a 6-wk period provided evidence of clonal evolution of LTC-IC in vitro. Leukemic chronic myelogenous leukemia LTC-IC were also infected at high efficiency using the same supernatant infection strategy with growth factor supplementation. These data demonstrate the feasibility of using cell-free virus preparations for infecting clinical marrow samples suitable for transplantation, as well as for further analysis of human marrow stem cell dynamics in vitro. PMID- 1601992 TI - Alterations in left ventricular diastolic function in conscious dogs with pacing induced heart failure. AB - We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327 +/- 105 mmHg/s and ejection fraction by -22 +/- 2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., tau increased by +14.0 +/- 2.8 ms and the myocardial stiffness constant by +6.5 +/- 1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV end-systolic (+28.6 +/- 5.7 g/cm2) and LV end-diastolic stresses (+40.4 +/- 5.3 g/cm2). When stresses and heart rate were matched at the same levels in the control and failure states, the increases in tau and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition. PMID- 1601993 TI - Potentiation of tubuloglomerular feedback in the rat by thromboxane mimetic. Role of macula densa. AB - Because endogenous thromboxane A2 (TXA2) potentiates the tubuloglomerular feedback response (TGF), we studied the mechanism of action of TXA2 by using a stable TXA2/prostaglandin (PG) H2 mimetic, U-46,619. Intravenous infusion of U 46,619 at 100 ng.kg-1.min-1 reduced the GFR and the single-nephron (SN)GFR measured from the distal tubule (macula densa function intact), whereas the SNGFR measured from the proximal tubule (macula densa function interrupted) was not changed consistently. 10-100-fold higher rates of infusion of U-46,619 were required to raise blood pressure or femoral vascular resistance. The regulation of glomerular capillary pressure (PGC) by TGF was assessed in anesthetized rats from changes in proximal stop flow pressure (PSF) and/or SNGFR during perfusion of the loop of Henle (LH) with artificial tubular fluid (ATF). Orthograde loop perfusion and retrograde perfusion of U-46,619 into the macula densa segment reduced PSF. Responses to luminal U-46,619 were blunted by a TXA2-PGH2 receptor antagonist. Orthograde loop perfusions with luminal U-46,619 increased net Cl absorption, whereas coperfusion with furosemide (10(-4) M) blunted the response to U-46,619 by 68%. These data indicated that the luminal U-46,619 might increase the signal for TGF activation by increasing Cl reabsorption in macula densa cells. However, since 80 +/- 4% of [3H]U-46,619 perfused via the LH was reabsorbed peritubular capillaries (PTC) were perfused with U-46,619 to test additional extra-luminal actions. PTC perfusion with U-46,619 again increased TGF by reducing PSF selectively only while macula densa function was intact during perfusion of the LH with ATF. CONCLUSIONS: (a) TGF is potentiated by U-46,619 given systematically, via the lumen of the LH by orthograde or retrograde perfusions or via the PTC; (b) at the lower doses tested, reduction of PGC and SNGFR by U-46,619 depends on tubular fluid delivery and reabsorption by the macula densa; (c) potentiation of TGF by U-46,619 entails preglomerular vasoconstriction which may be elicited in part by an increased signal due to increased net chloride reabsorption in the LH and presumably macula densa cells and by an increased sensitivity of the arteriole to macula densa-derived signals; (d) activation of TGF may contribute to the selective vasoconstriction of the renal vascular bed by low doses of U-46,619. PMID- 1601994 TI - Production of the Pseudomonas aeruginosa neuraminidase is increased under hyperosmolar conditions and is regulated by genes involved in alginate expression. AB - The pathogenesis of Pseudomonas aeruginosa infection in cystic fibrosis (CF) is a complex process attributed to specific characteristics of both the host and the infecting organism. In this study, the properties of the PAO1 neuraminidase were examined to determine its potential role in facilitating Pseudomonas colonization of the respiratory epithelium. The PAO1 neuraminidase was 1000-fold more active than the Clostridium perfringens enzyme in releasing sialic acid from respiratory epithelial cells. This effect correlated with increased adherence of PAO1 to epithelial cells after exposure to PAO1 neuraminidase and was consistent with in vitro studies demonstrating Pseudomonas adherence to asialoganglioside receptors. The regulation of the neuraminidase gene nanA was examined in Pseudomonas and as cloned and expressed in Escherichia coli. In hyperosmolar conditions neuraminidase expression was increased by 50% (P less than 0.0004), an effect which was OmpR dependent in E. coli. In Pseudomonas the osmotic regulation of neuraminidase production was dependent upon algR1 and algR2, genes involved in the transcriptional activation of algD, which is responsible for the mucoid phenotype of Pseudomonas and pathognomonic for chronic infection in CF. Under the hyperosmolar conditions postulated to exist in the CF lung, nanA is likely to be expressed to facilitate the initial adherence of Pseudomonas to the respiratory tract. PMID- 1601995 TI - Low density lipoprotein is protected from oxidation and the progression of atherosclerosis is slowed in cholesterol-fed rabbits by the antioxidant N,N' diphenyl-phenylenediamine. AB - The oxidative modification of low density lipoprotein (LDL) may play an important role in atherosclerosis. We found that the antioxidant N,N'-diphenyl-1,4 phenylenediamine (DPPD) inhibits in vitro LDL oxidation at concentrations much lower than other reported antioxidants. To test whether DPPD could prevent atherosclerosis, New Zealand White rabbits were fed either a diet containing 0.5% cholesterol and 10% corn oil (control group) or the same diet also containing 1% DPPD (DPPD-fed group) for 10 wk. Plasma total cholesterol levels were not different between the two groups, but DPPD feeding increased the levels of triglyceride (73%, P = 0.007) and HDL cholesterol (26%, P = 0.045). Lipoproteins from DPPD-fed rabbits contained DPPD and were much more resistant to oxidation than control lipoproteins. After 10 wk, the DPPD-fed animals had less severe atherosclerosis than did the control animals: thoracic aorta lesion area was decreased by 71% (P = 0.0007), and aortic cholesterol content was decreased by 51% (P = 0.007). Although DPPD cannot be given to humans because it is a mutagen, our results indicate that orally active antioxidants can have antiatherosclerotic activity. This strongly supports the theory that oxidized LDL plays an important role in the pathogenesis of atherosclerosis. PMID- 1601996 TI - Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. AB - We have examined integrin expression during the remodeling of the epidermis that takes place during wound healing, using a suction blister model in which the epidermis is detached from the dermis, leaving the basement membrane intact. By immunofluorescence microscopy, we found that the same integrin subunits were expressed during wound healing as in normal epidermis with very little change in the relative intensity or distribution of staining at the leading edge of the migrating epidermis. However, at the time of wound closure, when the epidermis is still hyperproliferative, alpha 2, alpha 3, alpha 6, and beta 1 were no longer confined to the basal layer, as in normal epidermis, but were also found in all the living suprabasal cell layers, coexpressed with the terminal differentiation markers involucrin, keratin 10, and keratin 16. Strong suprabasal staining for alpha v was also found in one specimen. beta 4, which normally forms a heterodimer with alpha 6, and alpha 5 remained predominantly basal. Three of the integrin ligands, fibronectin, type IV collagen, and laminin, remained largely confined to the basement membrane zone and dermis. By 14 d after wounding, the integrins were once more restricted to the basal layer. Suprabasal integrin expression was also observed in involved psoriatic lesions. Thus, in two situations in which the epidermis is hyperproliferative, there is a failure to downregulate integrin expression on initiation of terminal differentiation. The functional consequences of this aberrant integrin expression remain to be explored. PMID- 1601997 TI - A novel point mutation in the human insulin gene giving rise to hyperproinsulinemia (proinsulin Kyoto). AB - We have identified a 65-yr-old nonobese Japanese man with diabetes mellitus, fasting hyperinsulinemia (150-300 pM), and a reduced fasting C-peptide/insulin molar ratio of 2.5-3.0. Fasting hyperinsulinemia was also found in his son and daughter. Analysis of insulin isolated from the serum of the proband and his son by reverse-phase high performance liquid chromatography revealed a minor peak coeluting with human insulin and a major peak of proinsulin-like materials. The insulin gene of the patient was amplified by the polymerase chain reaction and the products were sequenced. A novel point mutation was identified in which guanine was replaced by thymine. The substitution gives rise to a new HindIII recognition site and results in the amino acid replacement of leucine for arginine at position 65. These results indicate that the amino-acid replacement prevents recognition of the C-peptide-A chain dibasic protease and results in an elevation of proinsulin-like materials in the circulation. Furthermore, in this family the proinsulin-like materials is due to a biosynthetic defect, inherited as an autosomal dominant trait. Rapid detection of this mutation can be accomplished by HindIII restriction enzyme mapping of polymerase chain reaction generated DNA, which enables us to facilitate the diagnosis and screening. PMID- 1601998 TI - Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. AB - Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia. PMID- 1601999 TI - Vertical transmission of human immunodeficiency virus (HIV) infection. Reactivity of maternal sera with glycoprotein 120 and 41 peptides from HIV type 1. AB - The observation that approximately 70% of HIV-infected pregnant women do not transmit infection vertically suggests that antibody therapy may be effective in the prevention of transmission of HIV infection from mother to child. Currently, there is an incomplete understanding of the processes involved in vertical transmission of HIV infection. The elucidation of the serological basis of maternal immunity as it relates to protection from vertical transmission is the goal of this study. We have screened 20 maternal sera from HIV+ individuals of known vertical transmission status for reactivity with 31 peptides spanning the entire envelope glycoprotein of HIV-1. Of interest was reactivity to regions outside of the V3 loop of gp120. The findings have been examined in relationship to transmission status, as well as to in vitro anti-HIV-1 biological activity. Our results indicate that lack of vertical transmission is correlated with high viral neutralization activity, but not with antisyncytial activity nor with binding to the V3 peptides examined in this study. Also, the transmission group bound to fewer gp41 peptides when compared with the nontransmission group, suggesting that immune responses to gp41 may be important in preventing transmission. These findings may provide insights into the design of passive immunotherapies. PMID- 1602000 TI - Lipoproteins containing the truncated apolipoprotein, Apo B-89, are cleared from human plasma more rapidly than Apo B-100-containing lipoproteins in vivo. AB - We have reported previously on two truncations of apolipoprotein B (apo B-40 and apo B-89) in a kindred with hypobetalipoproteinemia. Premature stop codons were found to be responsible for both apo B-40 and apo B-89, but the physiologic mechanisms accounting for the reduced plasma concentrations of these proteins have not been determined in vivo. This study investigates the metabolism of apo B 89 in two subjects heterozygous for apo B-89/apo B-100 and in one apo B-40/apo B 89 compound heterozygote. In both heterozygotes total apo B concentration is approximately 30% of normal and apo B-89 is present in lower concentrations in plasma than apo B-100. After the administration of [1-13C]leucine as a primed constant infusion over 8 h, 13C enrichments of plasma leucine as well as enrichments of VLDL-, IDL-, and LDL-apo B-89 leucine and VLDL-, IDL-, and LDL-apo B-100 leucine were measured over 110 h. Enrichment values were subsequently converted to tracer/tracee ratios and a multicompartmental model was used to estimate metabolic parameters. In both apo B-89/apo B-100 heterozygotes apo B-89 and apo B-100 were produced at similar rates. Respective transport rates of apo B 89 and apo B-100 for subject 1 were 2.13 +/- 0.18 and 2.56 +/- 0.13 mg.kg-1.d-1, and for subject 2, 6.59 +/- 0.18 and 8.23 +/- 0.39 mg.kg-1.d-1. However, fractional catabolic rates of VLDL, IDL, and LDL particles containing apo B-89 were 1.4-3 times higher than the rates for corresponding apo B-100-containing particles. Metabolic parameters of apo B-89 in the apo B-40/apo B-89 compound heterozygote compared favorably with those established for apo B-89 in apo B 89/apo B-100 heterozygotes. Thus, the enhanced catabolism of VLDL, IDL, and LDL particles containing the truncated apolipoprotein is responsible for the relatively low levels of apo B-89 seen in these subjects. PMID- 1602001 TI - Cl- secretion in a model intestinal epithelium induced by a neutrophil-derived secretagogue. AB - A secreted product of activated neutrophils, NDS (neutrophil-derived secretagogue), elicits a short circuit current (Isc) in epithelial monolayers derived from the human intestinal cell line T84 (J. Clin. Invest. 1991. 87:1474 1477). Here, we identify and characterize the source of this Isc and examine associated signaling pathways. 125I efflux studies suggested that NDS activates an anion conductive channel. Bidirectional 22Na 36Cl flux studies showed that electrogenic Cl- secretion fully accounts for the NDS-induced Isc response. NDS behaved in many respects as a cAMP-mediated secretagogue: NDS did not further increase maximal cAMP-induced Cl- secretion; NDS potentiated Ca(2+)-mediated Cl secretion; and NDS elicited measurable 125I but not 86Rb effluxes. However, NDS did not elicit a detectable rise in intracellular cAMP. Such data suggest that NDS may elicit Cl- secretion by effecting distal events in the cAMP-mediated pathway. Data derived from cell volume assays of isolated guinea pig intestinal crypt cells indicated that NDS also directly elicits Cl- secretion from natural intestinal epithelia. Additionally, since NDS activity is released from PMN by stimuli normally present in the colonic lumen, since NDS is active when applied apically to this model intestinal epithelium, and since the NDS-elicited Isc response is indicative of electrogenic chloride secretion, we speculate NDS may contribute to the secretory diarrhea encountered in many patients with inflammatory intestinal disease. PMID- 1602002 TI - Serological cross-reactivity between a human Ro/SS-A autoantigen (calreticulin) and the lambda Ral-1 antigen of Onchocerca volvulus. AB - We have cloned and sequenced a 46-kD Ro/SS-A autoantigen gene that is the human homologue of the calcium-binding protein, calreticulin. The sequence of this 46 kD Ro/SS-A protein (calreticulin) has significant homology to lambda Ral-1, a recombinant cDNA clone corresponding to a major antigen of the nematode, Onchocerca volvulus, the infectious agent of onchocerciasis. We therefore sought to determine whether antibodies produced by onchocerciasis patients might crossreact with the human 46-kD Ro/SS-A autoantigen (calreticulin). 20 of 22 sera from Liberian onchocerciasis patients who had no known evidence of autoimmune disease were found to contain antibodies that reacted with the 46-kD Ro/SS-A (calreticulin) by immunoblot analysis. Characteristic of sera reactive with Ro/SS A antigens, some onchocerciasis sera also immunoprecipitated the Ro/SS-A associated hY RNAs. In addition, a monoclonal antibody raised against O. volvulus organisms reacted to purified human WiL-2 cell 46 kD Ro/SS-A antigen (calreticulin) by ELISA. These results strongly suggest that onchocerciasis patients produce antibodies that crossreact with the 46-kD human Ro/SS-A autoantigen (calreticulin) and raise the possibility that infectious organisms such as O. volvulus might play a triggering or exacerbating role in the human Ro/SS-A autoimmune response. PMID- 1602003 TI - Alkaline phosphatase induces the mineralization of sheets of collagen implanted subcutaneously in the rat. AB - To determine whether alkaline phosphatase (ALP) can cause the mineralization of collagenous matrices in vivo, bovine intestinal ALP was covalently bound to slices of guanidine-extracted demineralized bovine dentin (DDS). The preparations were implanted subcutaneously over the right half of the rat skull. Control slices not treated with the enzyme were implanted over the left half of the skull of the same animals. Specimens were harvested after periods varying from 1 to 4 wk. It was shown that ALP-coupled DDS rapidly accumulated hydroxyapatite crystals. 4 wk after implantation, the content of calcium and phosphate per microgram of hydroxyproline amounted up to 80 and 60%, respectively, of that found in normal bovine dentin. Our observations present direct evidence that ALP may play a crucial role in the induction of hydroxyapatite deposition in collagenous matrices in vivo. PMID- 1602004 TI - Bile acid N-acetylglucosaminidation. In vivo and in vitro evidence for a selective conjugation reaction of 7 beta-hydroxylated bile acids in humans. AB - The aim of this study was to define whether N-acetylglucosaminidation is a selective conjugation pathway of structurally related bile acids in humans. The following bile acids released enzymatically from N-acetylglucosaminides were identified: 3 alpha,7 beta-dihydroxy-5 beta-cholanoic (ursodeoxycholic), 3 beta, 7 beta-dihydroxy-5 beta-cholanoic (isoursodeoxycholic), 3 beta,7 beta-dihydroxy-5 alpha-cholanoic (alloisoursodeoxycholic), 3 beta,7 beta-dihydroxy-5-cholenoic, 3 alpha,7 beta,12 alpha-trihydroxy-5 beta-cholanoic, and 3 alpha,6 alpha,7 beta trihydroxy-5 beta-cholanoic acids. The selectivity of conjugation was studied by administration of 0.5 g ursodeoxycholic (UDCA) or hyodeoxycholic (HDCA) acids, labeled with 13C, to patients with extrahepatic cholestasis, and of 0.5 g of 13C labeled chenodeoxycholic acid (CDCA) to patients with extra- or intrahepatic cholestasis. After administration of [24-13C]-CDCA, labeled glucosides, and the glucuronide of CDCA were excreted in similar amounts. Labeled N acetylglucosaminides of UDCA and isoUDCA were also formed. When [24-13C]-UDCA was given, 13C-label was detected in the N-acetylglucosaminide, the glucosides, and the glucuronide of UDCA, and in the N-acetylglucosaminide of isoUDCA. In the patient studied, 32% of the total UDCA excreted in urine was conjugated with N acetylglucosamine. In contrast, 96% of the excreted amount of [24-13C]HDCA was glucuronidated, and 13C-labeled glucosides but no N-acetylglucosaminide were detected. The selectivity of N-acetylglucosaminidation towards bile acids containing a 7 beta-hydroxyl group was confirmed in vitro using human liver and kidney microsomes and uridine diphosphate glucose (UDP)-N-acetylglucosamine. These studies show that N-acetylglucosaminidation is a selective conjugation pathway for 7 beta-hydroxylated bile acids. PMID- 1602005 TI - Magnesium relaxes arterial smooth muscle by decreasing intracellular Ca2+ without changing intracellular Mg2+. AB - Elevations in extracellular [Mg2+] ([Mg2+]o) relax vascular smooth muscle. We tested the hypothesis that elevated [Mg2+]o induces relaxation through reductions in myoplasmic [Ca2+] and myosin light chain phosphorylation without changing intracellular [Mg2+] ([Mg2+]i). Histamine stimulation of endothelium-free swine carotid medial tissues was associated with increases in both Fura 2- and aequorin estimated myoplasmic [Ca2+], myosin phosphorylation, and force. Elevated [Mg2+]o decreased myoplasmic [Ca2+] and force to near resting values. However, elevated [Mg2+]o only transiently decreased myosin phosphorylation values: sustained [Mg2+]o-induced decreases in myoplasmic [Ca2+] and force were associated with inappropriately high myosin phosphorylation values. The elevated myosin phosphorylation during [Mg2+]o-induced relaxation was entirely on serine 19, the Ca2+/calmodulin-dependent myosin light chain kinase substrate. Myoplasmic [Mg2+] (estimated with Mag-Fura 2) did not significantly increase with elevated [Mg2+]o. These results are consistent with the hypothesis that increased [Mg2+]o induces relaxation by decreasing myoplasmic [Ca2+] without changing [Mg2+]i. These data also demonstrate dissociation of myosin phosphorylation from myoplasmic [Ca2+] and force during Mg(2+)-induced relaxation. This finding suggests the presence of a phosphorylation-independent (yet potentially Ca(2+)-dependent) mechanism for regulation of force in vascular smooth muscle. PMID- 1602006 TI - A new variant of Glanzmann's thrombasthenia (Strasbourg I). Platelets with functionally defective glycoprotein IIb-IIIa complexes and a glycoprotein IIIa 214Arg----214Trp mutation. AB - We describe a new variant of Glanzmann's thrombasthenia (variant Strasbourg I). The patient (M.S.) showed an absence of platelet aggregation to ADP, thrombin, and collagen, and a decreased clot retraction. Platelet fibrinogen was approximately 20% of normal levels. ADP-stimulated platelets bound markedly reduced amounts of soluble fibrinogen and platelet adhesion to surface-bound fibrinogen was defective. Normal to subnormal amounts of glycoprotein (GP) IIb IIIa (alpha IIb beta 3) complexes, the platelet fibrinogen receptor, were revealed by SDS-PAGE, crossed immunoelectrophoresis, and antibody binding. However, the complexes were unusually sensitive to dissociation with EDTA at room temperature. Furthermore, flow cytometry showed that the platelets failed to bind the activation-dependent monoclonal antibody, PAC-1, after stimulation. In contrast, an RGDS-containing peptide induced significant binding of the anti ligand-induced binding site antibody, D3GP3, suggesting the presence of a functional RGD binding domain on the patient's GPIIb-IIIa complex. Sequence analysis was performed after polymerase chain reaction amplification of selected patient's GPIIIa exons, and of the patient's platelet GPIIb and GPIIIa mRNAs. A point mutation (C to T) was localized in exon D (iv) of GPIIIa that resulted in an 214Arg to 214Trp amino acid substitution. The defect has been inherited from the parents who are heterozygous for the same mutation. This substitution points to an essential amino acid in a region of GPIIIa involved in the binding of fibrinogen and influencing the Ca(2+)-dependent stability of the GPIIb-IIIa complex. PMID- 1602008 TI - Renal permeability alteration precedes hypertension and involves bradykinin in the spontaneously hypertensive rat. AB - Vascular permeability disorders have been described in experimental models, as well as in human hypertension. We recently described the fact that vascular permeability to albumin is heterogeneous in the normal rat. In the present study, we examine the contents of Evans blue dye (EB) bound to albumin in selected organs of unanesthetized Wistar Kyoto (WKY) and in spontaneously hypertensive rats (SHR) at various stages of development of hypertension. EB was injected in the caudal vein of paired 4, 8, 12, and 16-wk-old WKY and SHR. Rats were killed 10 min after EB injection and extraction of the marker was measured in selected tissues. In additional 4 and 16-wk-old animals, bradykinin B1 and B2 receptor antagonists (BKA) were also injected with EB. Renal contents of EB bound to albumin were higher in the SHR than in the WKY: 196 +/- 9, 202 +/- 10, 182 +/- 7, and 196 +/- 9, compared with 158 +/- 8, 155 +/- 7, 138 +/- 7, and 118 +/- 6 micrograms/g dry tissue, in the 4, 8, 12, and 16-wk-old rats, respectively. In the 4-wk-old SHR and WKY, blood pressure values were normal and comparable, yet the alteration in EB permeability was already present in the SHR. Both BKA failed to alter the renal EB extravasation in the WKY, but the B2-BKA restored the renal permeability to control levels in the SHR. We conclude that a selective defect in the renal vascular permeability to EB developed in the SHR. Since this finding precedes hypertension and is corrected by a selective B2-BKA, it is suggested that bradykinin is involved at an early stage of the disease in the SHR. PMID- 1602007 TI - Adrenergic mechanisms contribute to the late phase of hypoglycemic glucose counterregulation in humans by stimulating lipolysis. AB - Three studies were performed on nine normal volunteers to assess whether catecholamine-mediated lipolysis contributes to counterregulation to hypoglycemia. In these three studies, insulin was intravenously infused for 8 h (0.30 mU.kg-1.min-1 from 0 to 180 min, and 0.40 mU.kg-1.min-1 until 480 min). In study I (control study), only insulin was infused; in study II (direct + indirect effects of catecholamines), propranolol and phentolamine were superimposed to insulin and exogenous glucose was infused to reproduce the same plasma glucose (PG) concentration of study I. Study III (indirect effect of catecholamines) was the same as study II, except heparin (0.2 U.kg-1.min-1 after 80 min), 10% Intralipid (1 ml.min-1 after 160 min) and variable glucose to match PG of study II, were also infused. Glucose production (HGO), glucose utilization (Rd) [3 3H]glucose, and glucose oxidation and lipid oxidation (LO) (indirect calorimetry) were determined. In all three studies, PG decreased from approximately 4.8 to approximately 2.9 mmol/liter (P = NS between studies), and plasma glycerol and FFA decreased to a nadir at 120 min. Afterwards, in study I plasma glycerol and FFA increased by approximately 75% at 480 min, but in study II they remained approximately 40% lower than in study I, whereas in study III they rebounded as in study I (P = NS). In study II, LO was lower than in study I (1.69 +/- 0.13 vs. 3.53 +/- 0.19 mumol.kg-1.min-1, P less than 0.05); HGO was also lower between 60 and 480 min (7.48 +/- 0.57 vs. 11.6 +/- 0.35 mumol.kg-1.min-1, P less than 0.05), whereas Rd was greater between 210 and 480 min (19 +/- 0.38 vs. 11.4 +/- 0.34 mumol.kg-1.min-1, respectively, P less than 0.05). In study III, LO increased to the values of study I; between 4 and 8 h, HGO increased by approximately 2.5 mumol.kg-1.min-1, and Rd decreased by approximately 7 mumol.kg-1.min-1 vs. study II. We conclude that, in a late phase of hypoglycemia, the indirect effects of catecholamines (lipolysis mediated) account for at least approximately 50% of the adrenergic contribution to increased HGO, and approximately 85% of suppressed Rd. PMID- 1602009 TI - Homozygosity for the HLA-DRB1 allele selects for extraarticular manifestations in rheumatoid arthritis. AB - Seropositive rheumatoid arthritis is genetically linked to a group of HLA-DRB1 alleles sharing a sequence motif within the third hypervariable region. Controversy exists over the role of the distinct allelic variants in affecting not only the risk to develop disease, but also in modifying the expression of the disease. We have stratified 81 patients according to their patterns of disease manifestations and identified the HLA-DRB1 alleles by polymerase chain reaction amplification and subsequent oligonucleotide hybridization. To identify precisely the allelic combinations at the HLA-DRB1 locus, homozygosity was confirmed by locus-specific cDNA amplification and subsequent sequencing. Our study demonstrated a high correlation of allelic combinations of disease-associated HLA DRB1 alleles with the clinical manifestations. Characteristic genotypes were identified for patients who had progressed toward nodular disease and patients who had developed major organ involvement. Rheumatoid nodules were highly associated with a heterozygosity for two disease associated HLA-DRB1 alleles. Homozygosity for the HLA-DRB1*0401 allele was a characteristic finding for RA patients with major organ involvement. Our data suggest a role of the disease associated sequence motif in determining severity of the disease. The finding of a codominant function of HLA-DRB1 alleles suggests that the biological function of HLA-DR molecules in thymic selection might be important in the pathogenesis of RA. PMID- 1602010 TI - Germ line transcription of the immunoglobulin heavy chain locus directs production of mu chain without VDJ. AB - Immunoglobulin VDJ recombination is associated with transcriptional activation of the Ig variable region elements. We have previously described a novel Ig mu chain protein and mRNA produced by pre-B cell hybrids from normal and X-linked agammaglobulinemic bone marrow. We have now characterized the mRNA encoding this protein and find that it is composed of a 5' leader sequence spliced to C mu (LS C mu), lacking the variable (V), diversity (D), and joining (J) gene sequences. The leader sequence is encoded by a novel exon 16 kb upstream of the JH locus. Transcription of the germ line heavy chain locus from this LS exon results in transcriptional activation of the JH locus, apparently the initial step in commitment to B lymphoid development. Polymerase chain reaction amplification of normal bone marrow shows that these germ line LS-C mu transcripts are a product of bone marrow pre-B cells. Production of LS-C mu commences a sequential process of transcriptional activation, with concordant translation of Ig rearrangement intermediates, in the process of creating a productive VDJ rearrangement. PMID- 1602011 TI - Evidence for failure of V(D)J recombination in bone marrow pre-B cells from X linked agammaglobulinemia. AB - X-linked agammaglobulinemia (XLA) results from a failure of B lymphoid development. We have previously examined pre-B cell hybrids from three patients with XLA and found them to be limited to production of a novel germ line transcript of the Ig H chain locus composed of a leader sequence (LS) spliced to the constant region of mu chain (C mu) as mRNA and polypeptide. These transcripts result from transcriptional activation of the germ line heavy chain locus from an LS exon upstream of the embryonic JH locus. Germ line LS-C mu transcripts are produced by pre-B cells from normal bone marrow and fetal liver, indicating that they are products of normal pre-B cell development, as part of the process of transcriptional activation to provide access for the recombinase. Bone marrow from three patients with XLA has been examined directly by polymerase chain reaction amplification to determine whether the exclusive production of LS-C mu by XLA pre-B cell hybrids is representative of XLA pre-B cells. I report that LS C mu is the predominant Ig molecule produced by XLA pre-B cells, with limited production of the D mu product of DJH intermediate stage of V(D)J recombination. Mature VHDJH recombinations were not detected with a variety of primers that amplify VH sequences. I conclude that XLA is associated with a limitation in V(D)J recombination that may cause the failure of pre-B cell development. PMID- 1602012 TI - Intracellular calcium and ventricular function. Effects of nisoldipine on global ischemia in the isovolumic, coronary-perfused heart. AB - Ischemia-induced ventricular dysfunction has been shown to be associated with increased diastolic and systolic intracellular concentrations of free, ionized calcium ([Ca2+]i). The present study was designed to determine the effects of the Ca2+ antagonist nisoldipine on the relationship between [Ca2+]i and left ventricular contraction and relaxation during ischemia and reperfusion on a beat to-beat basis. Nine isovolumic coronary-perfused ferret hearts were made globally ischemic for 3 min and reperfused for 10 min. Ischemia and reperfusion were repeated during perfusion with a buffer containing 10(-8) M nisoldipine. From left ventricular developed pressure, time to peak pressure and time to 50% pressure decline were obtained. [Ca2+]i was determined with the bioluminescent protein aequorin. Global ischemia caused a rapid decline in contractile function and a significant increase in diastolic [Ca2+]i, from 0.35 to 0.81 microM, and in systolic [Ca2+]i, from 0.61 to 0.96 microM. During reperfusion, [Ca2+]i returned to baseline while ventricular function was still impaired. Relaxation was more affected than systolic contractile function. Nisoldipine significantly reduced the ischemia-induced rise in diastolic [Ca2+]i to 0.62 microM, and in systolic [Ca2+]i to 0.77 microM, and lessened the decrease in contractile function. Nisoldipine significantly accelerated the decline in [Ca2+]i during reperfusion and improved recovery of contractility and relaxation. These effects were associated with a significant diminution in ischemic lactate production. Taken together, our results provide direct quantitative evidence on a beat-to-beat basis that the calcium antagonist nisoldipine can ameliorate ischemia-induced abnormalities in [Ca2+]i handling, an effect that was associated with improved myocardial function during early reperfusion. PMID- 1602013 TI - Alternatively spliced variants of the insulin receptor protein. Expression in normal and diabetic human tissues. AB - Two insulin receptor mRNA transcripts resulting from alternative splicing of exon 11 in the receptor gene are expressed in a highly regulated tissue-specific fashion. To date, there is no information about the relative abundance of the protein isoforms encoded by these mRNAs in tissues of normal or diabetic subjects. We employed an antibody raised against the peptide sequence encoded by exon 11 to develop a specific immunoprecipitation assay that is capable of determining the fraction of receptors that include this amino acid sequence. The assay is based on the relative ability of the exon 11 specific monoclonal antibody (alpha IR alpha) compared to a nonspecific anti-receptor antiserum (B-2) to immunoprecipitate solubilized receptors that are first labeled with 125I insulin. The assay was validated using standard curves generated with samples composed of known ratios of the two receptor isoforms. Our results in general confirm observations regarding the relative abundance of the two mRNA species in human tissues, with marked predominance of the exon 11+ isoform in liver, and the exon 11- isoform in leukocytes. Similar amounts of both variants are present in placenta, skeletal muscle, and adipose tissue. In studies with this assay using skeletal muscle extracts from control and noninsulin-dependent diabetes mellitus (NIDDM) subjects, as well as in studies of the two mRNAs in control versus NIDDM muscle using a quantitative polymerase chain reaction assay, we could find no significant difference between control and diabetic subjects. This data contradicts a recent report claiming that normal individuals have only the exon 11- mRNA transcript in their skeletal muscle, whereas NIDDM subjects have similar expression of both mRNAs. Given the emerging evidence that functional differences exist between the two receptor isoforms, these studies are relevant to our understanding of insulin receptor function in health and disease. PMID- 1602016 TI - Bulimic women's perceptions of their family relationships. AB - This study examined the relationship between bulimia and family variables. Eight hundred twenty female college students completed a personal history questionnaire, the Bulimia Test, and the Eating Disorders Inventory. Twenty-four subjects who met the DSM-III-R criteria for bulimia were compared with 24 subclinical bulimics and 24 symptom-free subjects on demographic and family variables, including subscales from the Family Environment Scale and the Parental Bonding Instrument. Significant group differences indicated that the families of bulimics differ from other families. However, in contrast to the findings of research done in treatment settings, bulimics in this nonclinical setting did not report more family conflict or less caring from their parents than did symptom free subjects. PMID- 1602015 TI - Premilitary antecedents of post-traumatic stress disorder in an Oregon cohort. AB - The role of premilitary factors in the development of combat-related post traumatic stress disorder is unclear. A longitudinal survey of 52 Vietnam veterans, 48 Vietnam Era veterans (who served in the military, but not in Vietnam), and 51 nonveterans from an Oregon cohort suggests that while post traumatic stress disorder symptoms are associated with exposure to combat, level of combat is related to premilitary factors such as family SES and high school experience. Respondents from lower-social-class backgrounds were more likely to fail in school, and those who failed in school were more likely to enlist in the military and be sent to Vietnam. Those who experienced high levels of combat are more likely to have PTSD symptoms as long as 10 years after their return. PMID- 1602014 TI - The ATP-sensitive K+ channel mediates hypotension in endotoxemia and hypoxic lactic acidosis in dog. AB - Endotoxemia causes hypotension characterized by vasodilation and resistance to vasopressor agents. The molecular mechanisms responsible for these changes are unclear. The ATP-regulated K+ (K+ATP) channel has recently been found to be an important modulator of vascular smooth muscle tone which may transduce local metabolic changes into alterations of vascular flow. We report here that in endotoxic hypotension, the sulfonylurea glyburide, a specific inhibitor for the K+ATP channel, caused vasoconstriction and restoration of blood pressure. Glyburide also induced vasoconstriction and restoration of blood pressure in the vasodilatory hypotension caused by hypoxic lactic acidosis, while it was ineffective in the hypotension induced by sodium nitroprusside. Thus, vasodilation and hypotension in septic shock are, at least in part, due to activation of the K+ATP channel in vascular smooth muscle, and anaerobic metabolism with acidosis is a sufficient stimulus for channel activation. Because anaerobic metabolism and acidosis are common features in shock of any etiology, sulfonylureas may be effective therapeutic agents in the treatment of shock. PMID- 1602017 TI - Behavior patterns in nonreferred children: replication of the factor structure of the Missouri Children's Behavior Checklist. AB - This study provided normative data with regard to the behavior classification system based on the Missouri Children's Behavior Checklist (MCBC) with a sample of 120 nonreferred children. The factor structure of the MCBC replicated with a high degree of congruence. Application of the MCBC behavior classification system provided information on the frequency of problem patterns and problem-free patterns by nonreferred children. Variability in MCBC factor scores and behavior patterns was examined as a function of demographic parameters of gender, race, age, and socioeconomic status. PMID- 1602018 TI - Delinquent and criminal behavior as assessed by the revised California Psychological Inventory. AB - The revised California Psychological Inventory was studied in samples of 272 delinquent or criminal men vs. 1,088 controls, and 400 delinquent or criminal women vs. 2,266 controls, which gave delinquency base rates of 20% for men and 15% for women. Of the 27 scales evaluated, significant (p less than or equal to .01) mean differences were found on 25 for men and 26 for women. The best differentiator was So (Socialization), with point-biserial correlations of .54 for men and .58 for women. The new CPI theoretical model of personality structure also revealed significant differences. Persons in the Gamma and Delta lifestyle categories manifested higher rates of delinquency than did those in the Alpha and Beta. Low levels of ego integration were associated with greater incidence of delinquency in all four lifestyles. PMID- 1602019 TI - Psychometric properties of the Interpersonal Style Inventory. AB - This study investigated the reliabilities and conjectured factor structure of the subscales comprised by Lorr and DeJong's (1986) abbreviated form of the Interpersonal Style Inventory (ISI). The results suggest that internal consistency reliabilities of the subscales are presently inadequate for clinical or research purposes. The five-factor structure described by Lorr (1986) appeared to conform well to the empirical grouping in the data set. Only one scale, Approval Seeking, appeared incorrectly placed according to the a priori description. Another weakness in the a priori structure was that the Rule-Free subscale had only a minor role in identifying its conjectured factor. These results were based on ISI protocols from 268 adults. Overall's (1974) marker variable factor analysis was implemented to assess the adequacy of the a priori factor structure. PMID- 1602020 TI - Mexican-Americans' performance on the Psychological Screening Inventory as a function of acculturation level. AB - The present study investigated 261 Mexican-American college students' performance on the Psychological Screening Inventory (PSI), a brief personality instrument designed to detect persons who might benefit from more extensive evaluations in mental health settings. In addition to providing PSI results against which other Hispanic-American populations can be compared, this study examined the relationship between the acculturation level of the subjects and their PSI performance. Only one of the five PSI subscales (Alienation) correlated significantly with acculturation, which suggests that increases in acculturation are associated with fewer feelings of alienation. PMID- 1602021 TI - MCMI-II personality disorders in recent-onset bipolar disorders. AB - This study investigated the personality disorders of 21 recent-onset Bipolar Disorder patients using the revised Million Clinical Multiaxial Inventory (MCMI II; Millon, 1987). Personality disorder assessments, conducted after patients' clinical symptoms had settled, indicated that 17 patients received at least one MCMI-II personality disorder diagnosis with a trend toward multiple diagnoses. Narcissistic, Antisocial, and Histrionic personality disorders were diagnosed most frequently and were the scales most elevated. Schizoid and Compulsive personality disorders were the scales least elevated. Diagnostic concordance between the MCMI-II and the Structured Interview for DSM-III Personality (SIDP; Pfohl, Stangl, & Zimmerman, 1983) was poor; the MCMI-II made more multiple diagnoses. Implications of the discrepancies between these instruments and suggestions for future research are discussed. PMID- 1602022 TI - MMPI-2: reliability with college students. AB - This study examined the temporal stability and internal consistency of the MMPI-2 in a sample of 128 college students. Mean score comparisons revealed significant differences across a number of scales, but in each case mean differences were slight and viewed as clinically insignificant. Moderate to high stability coefficients were obtained, from .60 to .90 (median of .74). Alpha coefficients ranged from .39 to .91 (median of .62). Analysis of individual difference scores revealed that for each scale approximately 20% of the sample had discrepancy scores that reached or exceeded 10 T-score points (i.e., one standard deviation). Findings are discussed relative to the reliability of the MMPI-2 in clinical assessment. PMID- 1602023 TI - Reliability and validity of the Turkish version of the Automatic Thoughts Questionnaire. AB - The present study investigated the reliability and validity of the ATQ in the Turkish cultural context. It is hoped that with this type of cross-cultural information, the universality of the proposed cognitive constructs can be advocated more reliably. The subjects were 345 university students; the split half reliability of the ATQ was found to be r = .91 and Cronbach's alpha was .93; and item/total correlations ranged between .36 and .69. The Turkish ATQ correlated well with the BDI (r = .75), and it discriminated successfully between the symptomatic and asymptomatic groups. Factor analysis revealed five factors that were similar to those found in American samples. Nevertheless, some differences were noticed in the relative strength of the factors and in the distribution of items into factor clusters. PMID- 1602024 TI - Recall of clustered and unclustered word lists in elderly adults. AB - We present descriptive data for alternate forms of clustered and unclustered word list recall in 102 healthy elderly adults and test results for 11 patients with Parkinson's disease. The word list test provided a relatively stable measure of verbal memory. Alternate forms were equivalent except for a tendency of the unclustered list of Form 1 to be easier than those of the other three forms. Verbal intelligence, total word recall, and the ability to cluster related words at recall were related significantly. There were modest effects of education on word recall; female subjects tended to recall more words than males. PMID- 1602025 TI - Comparison of two methods for converting the WAIS to the WAIS-R. AB - Two methods for converting WAIS scores to WAIS-R scores were investigated. One method subtracted the mean differences between the WAIS and WAIS-R IQs and subtests means from the WAIS scores. The other method converted the WAIS and WAIS R scores to T scores. Theoretically, the two methods should produce equivalent results. Because the SDs for the WAIS and WAIS-R were quite similar, the only components that remained to produce the difference were the means. Using 52 pairs of WAIS and WAIS-R scores, matched by age and education, both methods were compared. There was no statistically significant difference between the methods. Two new norming methods were discussed in terms of these results. PMID- 1602026 TI - The relationship between intellectual ability and adult performance on the Trail Making Test and the Symbol Digit Modalities Test. AB - Subjects between the ages of 18 and 30 were divided in groups based on their Satz Mogel Wechsler Adult Intelligence Scale-Revised Full Scale IQs: (a) Borderline (70 to 79); (b) Low Average (80 to 89); (c) Average (90 to 109); (d) High Average (110 to 119); (e) Superior (120 to 129). Each subject was administered the Trail Making Test (Forms A and B) and the written version of the Symbol Digit Modalities Test. A significant effect for IQ emerged. The low ability subjects were, in the main, significantly different from the higher ability subjects. No gender differences were found. PMID- 1602027 TI - Validity of two short forms of the WISC-R in children with traumatic brain injury. AB - The validities of Kaufman's (1976) four-subtest short form and Kennedy and Elder's (1982) five-subtest short form for the WISC-R were evaluated in 98 children with traumatic brain injury. Both forms correlated highly with actual WISC-R FSIQ, and both forms had acceptable relationships to measures of injury severity. However, the Kaufman method had a larger standard error of measurement than did the Kennedy and Elder method, and the Kaufman method tended to overestimate actual FSIQ. It was concluded that the Kennedy and Elder short form for the WISC-R may be a relatively more accurate predictor of actual FSIQ in children with traumatic brain injury. PMID- 1602028 TI - Learning styles of LD and NLD ADHD children. AB - Attention Deficit Hyperactive Disorder (ADHD) children (N = 26) with a learning disability (LD) and without (NLD) were compared on measures of information processing using the Learning Efficiency Test (LET). Method of presentation (visual vs. auditory), order of recall (ordered vs. non-ordered), and memory processes (immediate, short-term, and long-term) were assessed. While both groups showed more difficulty with short-term and long-term memory processes than with immediate memory processes, the ADHD-LD subjects demonstrated more difficulty processing information effectively. Ordered recall was significantly more difficult for both short-term and long-term memory processes than was unordered recall. While both groups demonstrated difficulty with auditory ordered recall under short-term and long-term conditions, the ADHD-LD subjects lost the most information under auditory conditions. PMID- 1602029 TI - Posttreatment adjustment of clients who drop out early vs. late in treatment. AB - Symptom improvement from intake until 4 months later was assessed for 33 adult and 35 child psychotherapy drop-outs. Client ratings, therapist ratings, and symptom checklist changes were used as measures. Early drop-outs (one or two visits) were less well adjusted than late drop-outs (three or more visits) for both adults and children, though the difference was stronger for adults. Few differences were found between late drop-outs and completers. It was concluded that outcome researchers should use routinely the same procedures for assessing drop-outs' and completers' outcomes and that improvement of early and late drop outs should be distinguished. PMID- 1602030 TI - Relaxation therapy as an adjunct in radiation oncology. AB - Stress, anxiety, and depression in patients who are undergoing treatment of cancer significantly compromise the quality of their lives. The impact of stress reduction by relaxation training and imagery was studied in 82 out-patients who were undergoing curative (73 patients) or palliative (9 patients) radiotherapy. Fifty-two females and 30 males were assigned randomly to a relaxation training condition (34 patients) as an adjunct to radiation or a control condition (29 patients), which entailed education and counseling along with the RT. Using pre- and posttests of the Profile of Mood States, significant (p less than .01) reductions were noted in the treatment group in tension, depression, anger, and fatigue. The results suggest that relaxation training substantially improves several psychological parameters associated with quality of life in ambulatory patients who are undergoing radiation therapy. PMID- 1602031 TI - The Rorschach and the DSM-III-R antisocial personality: a tribute to Robert Lindner. AB - This study utilized the Rorschach as a psychometric measure for understanding Antisocial Personality Disorder (American Psychiatric Association, 1987). Comprehensive System (Exner, 1986) Rorschach data for a sample of 60 ADP subjects and Rorschach object relations and defensive operations for 22 psychopathic APD (P-APD) and 21 nonpsychopathic APD (NP-APD) subjects are presented and discussed. The data support the absence of anxiety and attachment and the presence of pathological narcissism and borderline personality organization in P-APDs. The Rorschach's ability to differentiate antisocial groups based on level of psychopathy (Hare, 1980, 1985) strongly supports the need to use psychopathy as an independent measure when one is studying APD. PMID- 1602032 TI - The differential effects of parental alcoholism and mental illness on their adult children. AB - Growing up in a household with alcoholic or mentally ill parents is more likely to produce lower self-esteem, greater dysphoria, and more anxiety in adulthood. To test this hypothesis, 139 undergraduate and graduate students completed measures of anxiety, depression, social avoidance, self-esteem, and social support. Results showed that adult children of alcoholics, adult children of mentally ill, and adult children of substance-abusing mentally ill had lower self esteem and were more socially anxious than normal controls. Adult children of mentally ill parents were more depressed and showed greater trait anxiety than did adult children of alcoholics and controls. The impact of parental pathology is diminished when the adult child has a large and/or satisfactory social support network. PMID- 1602033 TI - The Children of Alcoholics Screening Test: reliability and relationship to family environment, adjustment, and alcohol-related stressors of adolescent offspring of alcoholics. AB - The Children of Alcoholics Screening Test (CAST) had acceptably high internal consistency (.88 and .90) and test-retest reliabilities (.88) when administered to adolescents from intact alcoholic families. CAST scores were unrelated to measures of adolescent adjustment or indices that reflect general family environment. However, CAST scores did correlate positively with a measure of the more specific family environment related to alcohol abuse. The study suggested that CAST scores are best suited for screening respondents and not as a dependent variable because the relationships that one is likely to identify between CAST scores and any other variable would be primarily reflective of group differences between offspring of alcoholics and nonalcoholics. PMID- 1602035 TI - The immediate- and medium-term effects of Meswak on the composition of mixed saliva. AB - Chewing sticks or Meswaks are used for teeth cleaning in many parts of the world. They contain substances that may reduce caries and periodontal disease. The present study consisted of 2 parts. In a short-term experiment, volunteers chewed on an inert eliciting agent (pyrogen-free rubber) and then a piece of Meswak, each for 5 min. For the medium-term experiment, volunteers brushed with either Meswak or a conventional toothbrush 5 x a day for 2 weeks. Saliva produced immediately after chewing Meswak showed statistically significant increases in calcium and chloride, but decreases in phosphate and pH as compared with controls. In the medium-term experiment, saliva samples collected 4 h after the last use of Meswak or toothbrush showed no significant differences in any of the components examined (calcium, magnesium, chloride, phosphate, IgA, IgG, lactate dehydrogenase and aspartate transaminase). Gingival and plaque indices, however, were significantly lower after brushing with Meswak. Salivary calcium promotes mineralization of tooth enamel and chloride inhibits calculus formation. Our results thus indicate that Meswak releases substances into saliva that could improve oral health. Calcium and chloride values were similar to those of controls after 4 h and thus frequent use of Meswak may be necessary to maintain a favorable salivary environment. PMID- 1602034 TI - Metronidazole in periodontitis: reduced need for surgery. AB - A considerable amount of circumstantial evidence indicates that most forms of periodontitis are due to the presence or dominance of a finite number of bacterial species in the subgingival plaque. Almost all of the putative pathogens are anaerobic species, indicating that most forms of periodontitis could be diagnosed as anaerobic infections. In this double-blind investigation, patients with elevated proportions or levels of spirochetes in 2 or more plaque samples, i.e., 60% spirochetes, were randomly assigned to receive either metronidazole, 250 mg 3 x a day for 1 week, or placebo (positive-control) after the completion of all debridement procedures. When the patients were re-examined 4 to 6 weeks later, the patients in the metronidazole group (n = 15) exhibited a highly significant (p less than 0.01) reduction in probing depth and apparent gain in attachment levels relative to the patients (n = 18) in the positive-control group about those teeth that initially had probing depths of 4 to 6 mm. This pattern was also observed about teeth that initially had probing depths greater than or equal to 7 mm. This reduction in probing depths and apparent gain in attachment was associated with a significant reduction in the need for periodontal surgery in the metronidazole-treated patients (difference 8.4 teeth per patient) compared to the positive-control patients (2.6 teeth per patient). These clinical improvements in the metronidazole group were associated with significantly lower proportions of spirochetes, selenomonads, motile rods, and P. intermedius, and a significantly higher proportion of cocci in the plaques. These findings indicate that systemic metronidazole, when given after all the root surface debridement is completed, leads to additional treatment benefits, including a reduced need for surgery, beyond that which can be achieved by debridement alone. PMID- 1602036 TI - Periodontal aspects of osseointegrated fixtures supporting a partial bridge. An up to 6-years retrospective study. AB - The present paper reports on the use of osseointegrated titanium fixtures (Branemark) in partially edentulous patients. The tissue reactions around 509 implants in 97 upper and 71 lower jaws of 146 consecutive patients, rehabilitated by means of partial bridges--supported by implants only (60%) or by the combination of teeth and implants (40%)--were observed longitudinally. The mean number of implants per bridge was 2.40 (range 1-5) for the upper jaw and 2.06 (range 1-5) for the lower jaw respectively. Before loading, a total of 23 fixtures were lost, 15 in the upper and 8 in the lower jaw. This loss could partially be correlated to per- and post-operative complications and to fixture characteristics (length, self-tapping or not). After a loading time of 30 months (range 2 to 77 months), 6 implants, 2 in the upper and 4 in the lower jaw, showed symptoms of non-integration. The cumulative failure rate for the individual fixtures after a 6-year period reached 5.7 and 6.5% for the upper and lower jaw, respectively. The mean annual marginal bone loss, scored on standardized radiographs, was 0.9 mm during the 1st year and 0.1 mm the following years. This loss in marginal bone height was equal in the upper and lower jaws and not related to the type of occlusal material of the bridges. The present data showed that the cumulative failure rate for Branemark implants supporting partial bridges can be limited to 6% after a 6-year period, and that the radiographic bone loss is comparable with that found around fixtures supporting full bridges. PMID- 1602037 TI - The effects of antimicrobial acrylic strips on the subgingival microflora in chronic periodontitis. AB - This study investigated the effects of root planing and/or the placement of acrylic strips containing chlorhexidine, metronidazole or tetracycline on the composition and antimicrobial susceptibility of the subgingival flora in chronic periodontitis. 101 periodontal pockets from 73 patients were entered into 6 treatment groups which were, chlorhexidine, metronidazole or tetracycline strips, root planing, root planing followed by metronidazole strips and a control, no treatment group. Total anaerobic counts and anaerobe/aerobe ratios were estimated from samples taken before treatment and 1, 2, 4, 8 and 12 weeks after treatment. In addition, a more detailed analysis of the effects of the treatments on the subgingival flora was carried out on 12 pockets in 12 patients. Tetracycline strips, metronidazole strips and root planing and metronidazole strips were more effective than chlorhexidine strips in causing reductions in total anaerobic count and anaerobe/aerobe ratio. However, the changes in microbial parameters rebounded to approach baseline levels 4 weeks after treatment. Chlorhexidine caused no detectable changes in the composition of the subgingival microflora, while metronidazole had a variable effect. Tetracycline appeared to effect major shifts in the composition of the microflora of treated pockets but caused a marked selection of tetracycline-resistant organisms. PMID- 1602038 TI - Resolution of cyclosporin A (CsA)-induced gingival enlargement following reduction in CsA dosage. AB - Gingival enlargement due to the immunosuppressive drug, cyclosporin A (CsA), will resolve following discontinuation of drug therapy or extraction of adjacent teeth. This report presents a clinical observation on a patient in whom CsA induced gingival enlargement failed to resolve with improved plaque control and scaling, but resolved quickly following reduction in the daily dosage of CsA. Despite less than optimal plaque control, the CsA-induced gingival enlargement did not recur on the reduced drug dosage over a 2-year observation period. This finding raises the possibility that reduction of CsA dosage below a certain critical level may lead to resolution of CsA-induced gingival enlargement. PMID- 1602039 TI - The effect of a combination of chlorhexidine diacetate, sodium fluoride and xylitol on plaque wet weight and periodontal index scores in military academy cadets refraining from mechanical tooth cleaning for 7-day experimental periods. AB - 45 subjects participated in a double-blind cross-over mouthwash study where a new tablet-form combination of chlorhexidine, fluoride and xylitol (XYLIHEX) was studied together with solutions of chlorhexidine (CHX) and sodium fluoride (NaF). The preparation XYLIHEX was developed as a dental chemotherapeutic that could easily be added to the soldiers' kit to be used under circumstances where practising normal oral hygiene habits is restricted. For comparative purposes, XYLIHEX was prediluted in this study to make a solution. Before starting, professional prophylaxis was given to the subjects to bring their gingivitis index scores as close to 0 as possible. The subjects refrained from mechanical tooth cleaning for three 7-day test periods. Plaque wet weight and periodontal index scores were recorded before and after the test periods. The results showed that the preparations XYLIHEX and CHX did not statistically differ from each other in reducing plaque wet weight values and the recorded periodontal index scores. Both these preparations were statistically highly significantly more effective antiplaque agents than NaF, as expected. PMID- 1602040 TI - Predictive power of various models for longitudinal attachment level change. AB - Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naive mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future. PMID- 1602041 TI - Clinical diagnosis of trauma from occlusion and its relation with severity of periodontitis. AB - The purpose of the present study was to determine the reliability of several selected signs of trauma from occlusion and their relations with severity of periodontitis. 32 moderate to advanced chronic periodontitis patients participated in the study. All teeth present were evaluated for various abnormal occlusal contacts, signs of trauma from occlusion, and the severity of periodontitis. Standardized periapical radiographs were also taken for each tooth. The results demonstrated that: (1) no significant difference occurred in probing pocket depth (PD), clinical attachment loss (AL), or percentage of alveolar bone height (BH) between teeth with and without various abnormal occlusal contacts, i.e., premature contacts in centric relation occlusion, non working contacts in lateral excursions, premature contacts of anterior teeth or posterior protrusive tooth contacts; (2) teeth with either significant mobility, functional mobility, or radiographically widened periodontal ligament space (PDLS) had deeper PD, more AL and lower BH than teeth without these signs, while teeth with pronounced wear or radiographically thickened lamina dura had less AL than teeth without these findings; (3) 2 combined indices, i.e., the trauma from occlusion index (TOI) and the adaptability index (AI), were proposed for the identification of occlusal trauma and the response of periodontium to excessive biting forces in heavy function, respectively; TOI-positive teeth exhibit deeper PD, more AL and less osseous support than TOI-negative teeth; however, AI positive teeth had less AL and more osseous support than AI-negative teeth; (4) with identical attachment level, TOI-positive teeth had less osseous support than TOI-negative teeth while the magnitude of difference became greater with an increase of attachment loss. PMID- 1602042 TI - Home accidents in Al-Khobar city, eastern province, Saudi Arabia: a case-control socioeconomic study. AB - A one-month prospective case-control study was conducted in two sectors of Al Khobar City (Saudi population of 65,070) with the objective of identifying the socioeconomic factors that are related to home accidents among Saudis. All accidents reported to 20 health facilities during the period were recorded and for the home accidents a questionnaire was completed at the Emergency Rooms (ERs) and the subjects were subsequently interviewed at their homes. Of the 1,104 Saudis who reported to the ERs of these health facilities 209 (18.9 percent) had home accidents. 206 were interviewed at home together with 448 families (controls) randomly drawn from the family folders at the primary health care centers in the two sectors. In the event 25 more home accidents were identified and the number of control families was accordingly reduced to 423 while the accidents increased to 231. The overall incidence rate was 355/100,000 Saudis per month, being lower (327.6/100,000) for the first sector (Al-Thougba) with a population of a relatively lower socioeconomic status than the second (Al-Khobar) sector (399.5/100,000). The number of home accidents was related to family size and was also larger in families living in villas and flats compared to single story and portable buildings. Families with home accidents had significantly more members than the controls. It is recommended that extensive community-oriented research be conducted to identify, evaluate, and subsequently control the environmental and human factors that contribute to the incidence and outcome of home accidents in Saudi Arabia. PMID- 1602043 TI - Dietitians' perceptions about and personal nutrition practices for cancer risk reduction. AB - This study was undertaken to examine the beliefs and practices of dietitians in relation to cancer risk reduction through nutrition. Respondents to the national survey (N = 384, 70 percent) were similar in demographic, educational, and professional characteristics to the American Dietetic Association census data. They reported a strong preventive health orientation: mean performance on 10 preventive health behaviors was 77.5 on a 100 point scale. Half (53 percent) believed cancer would be serious if they developed it, 47 percent believed it was not likely that they would. About 20 percent of the respondents felt that the role of nutrition in cancer etiology was unclear. Dietitians believed strong research support existed for increasing whole grains, fruits and vegetables, and fiber to reduce cancer risk but that little evidence supported use of dietary supplements. Dietitians regularly practiced 75 percent of nutrition recommendations they believed to be effective in reducing cancer risk. Beliefs about the effectiveness of a recommendation accounted for the largest percentage of variance on nutritional practices. While dietitians reported many preventive health practices, including following nutrition recommendations, they seemed to be doing so for reasons other than preventing cancer. PMID- 1602044 TI - Syphilis, AIDS and crack cocaine. PMID- 1602045 TI - Exchanging sex for crack-cocaine: a comparison of women from rural and urban communities. AB - Studies of the HIV risks of crack-cocaine using women have focused on those living in the inner city, urban areas of the country. However, reports indicate that the rates of syphilis and HIV infection have shown greater increases in rural areas than in urban ones. This paper reports the findings of a comparative study of 60 female crack-cocaine users, 25 from rural southeast Georgia and 35 from Miami, Florida, to determine their drug using and sexual practices, as well as their knowledge about AIDS and HIV transmission. Their patterns of initial and continuous drug use were similar, as were their sexual practices. However, the Miami women were more likely to have had a greater number of sexual partners than the Georgia women. Both groups were knowledgeable about AIDS and the transmission of HIV, yet all participated in activities that put them at high risk for HIV infection and transmission. Some 12 percent of the 60 respondents reported testing positive for HIV. The study suggests that at least within these populations, there are few differences between rural and urban crack using women in terms of their crack use, sexual practices, and potential for HIV infection and transmission. PMID- 1602046 TI - A Community Health Education System to meet the health needs of Indo-Chinese women. AB - This paper presents a Community Health Education System which is cost-effective, sustainable, strongly community-based, and directed at improving the health status of rural women in Indo-china (Kampuchea, Laos and Vietnam). The system is developed through a series of steps which are concerned with the education of Community Health Education Units (in national ministries of health) and, at the village level, among community health workers, women's groups, and other women. The ultimate aim is the establishment of a community health education program in Indochinese villages. PMID- 1602047 TI - Age and Pap smear history as a basis for intervention strategy. AB - As a means of developing effective intervention strategies for promoting Pap smear screening, we analyzed data from a population-based women's health survey (N = 603) in a 36-county area in southeastern Kentucky. The cervical cancer mortality rate for white women in this area is one of the highest in the United States. By using selected sociodemographic, health-care utilization, health knowledge, and health behavior variables in age-specific logistic regression models, we discriminated between women who had had a Pap smear within 3.5 years and those who had not. Several variables predicted Pap screening status regardless of the woman's age. Women of all age groups who had not been recently screened had encounters with the medical-care system. A key variable that affected use of screening services was ever use of birth control pills. The main differences between the three age groups were as follows: the 18-44 age group was less likely to see a private physician and less likely to seek medical care of any type, except for care related to pregnancy; only the 45-59 age group believed that cost of medical care was a problem; and only for the 60 or older age group were socioeconomic variables associated with not having recently had a Pap test. PMID- 1602048 TI - 5B4-CAM expression parallels neurite outgrowth and synaptogenesis in the developing rat brain. AB - In order to study whether 5B4-CAM expression parallels neurite outgrowth and synaptogenesis, a monoclonal antibody, 5B4, was used, which recognizes both fetal (185-250 kD) and adult (140 kD, 180 kD) forms of the neural cell adhesion molecule (N-CAM), to identify and localize the antigen in rat tissue during developmental ages P1 through P31 and in adults between P60 and 2 years of age. A ubiquitous pattern of intense immunolabelling was detected during the earliest stages of development. 5B4-CAM expression paralleled process outgrowth and the early stages of synaptogenesis in the cerebral cortex, hippocampal formation, and cerebellum. In the adult, immunoreactivity was generally less intense, but the cerebral cortex and hippocampal and cerebellar molecular layers, all areas implicated in learning-associated plasticity, retained substantial immunoreactivity. The inner one-third of the dentate gyrus molecular layer, an area implicated in axonal sprouting and reactive synaptogenesis, was particularly intensely labelled. Evidence from this work suggests that 5B4-CAM expression may be useful in monitoring neurite outgrowth and the early stages of synapse formation during development and possibly axonal sprouting and reactive synaptogenesis in the adult. PMID- 1602049 TI - GABAergic and non-GABAergic projections of accessory optic nuclei, including the visual tegmental relay zone, to the nucleus of the optic tract and dorsal terminal accessory optic nucleus in rat. AB - This study examines the non-gamma-amino butyric acid (GABA)ergic (group I neurons) and GABAergic neurons (group II neurons) of the accessory optic system projecting to the nucleus of the optic tract (NOT)/dorsal terminal nucleus (DTN) of the accessory optic system in rat. These nuclei include the dorsal (MTNd) and ventral (MTNv) divisions of the medial terminal nucleus, the lateral terminal nucleus, the interstitial nucleus of the superior fasciculus, the posterior fibers, and the visual tegmental relay zone. GABAergic neurons of these nuclei that do not target the NOT/DTN (group III neurons) have also been observed. The fluorescent retrograde tracer fluoro-gold was injected into the pretectum, targeting the NOT/DTN and the tissue prepared immunocytochemically to reveal neurons containing the neurotransmitter GABA. Three groups of neurons (groups I, II, and III neurons) were examined in terms of their distribution, density, and percentage present. Group I neurons are single-labeled with fluoro-gold and represent non-GABAergic neurons projecting to the NOT/DTN. These neurons are of the highest density in the lateral terminal nucleus (204 neurons/mm2). Their densities are also substantial in the MTNv (120 neurons/mm2), interstitial nucleus of the superior fasciculus, posterior fibers (96 neurons/mm2), and visual tegmental relay zone (93 neurons/mm2). Group II neurons are double-labeled with fluoro-gold and GABA. They form a system of GABAergic neurons projecting to the NOT/DTN, which are exceedingly dense in the MTNd (78 neurons/mm2) but are also dense in both the visual tegmental relay zone (49 neurons/mm2) and MTNv (33 neurons/mm2). Group III neurons are GABAergic neurons that do not target the NOT/DTN but must project to other brain nuclei and/or be interneurons. These are of extremely high concentration in the visual tegmental relay zone (316 neurons/mm2) and are also of substantial densities in the MTNd (77 neurons/mm2), lateral terminal nucleus (72 neurons/mm2), and MTNv (44 neurons/mm2). The MTNd has the highest percentage of GABAergic neurons projecting to the NOT/DTN (72%). GABAergic neurons also form significant percentages of the projections to the NOT/DTN from the visual tegmental relay zone (34%) and MTNv (21%). The percentage of the total GABAergic neurons that project to the NOT/DTN is the highest in the MTNd (50%) and MTNv (42%). The described GABAergic afferents to the NOT/DTN may function to process information concerned with the compensation for retinal slip. PMID- 1602050 TI - Distribution of neuropeptide Y-like immunoreactivity in the brain of the lizard Gallotia galloti. AB - The distribution of neuropeptide Y (NPY)-like immunoreactivity was studied in the brain of the lizard Gallotia galloti, in order to gain insight into the comparative topography of this peptide. Antisera against both NPY and its C terminal flanking peptide (C-PON) were used, demonstrating a general coexistence of both peptides, as described in other vertebrates. Most NPY-like immunoreactive (NPY-LI) cell bodies were observed in the telencephalon, specifically in various olfactory structures, all cortices, septum, basal ganglia (except for the globus pallidus), the nucleus of the diagonal band of Broca, the amygdaloid complex, and the bed nucleus of the anterior commissure. NPY-LI cells were also seen in the preoptic and hypothalamic regions and the dorsal thalamus (mainly in the perirotundal belt), as well as in the mesencephalic tegmentum (in the ventral tegmental area, the substantia nigra, and the retrorubral area). NPY-LI fibers and terminals were widely distributed in the brain. All visual and auditory neuropiles were densely innervated. Specially dense plexuses were seen in the nucleus accumbens, the ventral pallidum, the suprachiasmatic and ventromedial hypothalamic nuclei, the nucleus medialis thalami, the left habenula, and the central nucleus of the torus semicircularis. Our analysis shows that the distribution of NPY-like immunoreactivity in the forebrain of Gallotia largely resembles that of other vertebrates, whereas differences are mainly observed in the brainstem. The widespread distribution of NPY in the lizard brain suggests several modulatory functional roles, either in local-circuit systems of the forebrain, or in various limbic, neuroendocrine, and sensory pathways. PMID- 1602051 TI - Structural changes of the soleus and the tibialis anterior motoneuron pool during development in the rat. AB - The morphological development of motoneuron pools of two hindlimb muscles of the rat, soleus (SOL) and tibialis anterior (TA), was studied in rats ranging in age between 8 and 30 postnatal days (P8-P30). Motoneurons were retrogradely labelled by injecting a cholera toxin B subunit solution directly into the muscles. This resulted in extensive labelling of motoneurons as well as their dendritic trees. The distribution of cross sectional areas of neuronal somata was determined for both muscles at various ages. Somal size increased considerably between P8 and P12, whereas growth was moderate between P12 and P20. The size distribution of SOL motoneurons was bimodal from P20, whereas the size distribution of TA motoneurons remained largely unimodal. The morphological development of the dendritic tree was studied qualitatively. The development of dendritic arborization within the SOL and the TA motoneuron pool showed major differences. The arborization pattern of dendrites of TA motoneurons was basically multipolar at all ages. In contrast, dendrites of SOL neurons tended to line up with the rostro-caudal axis and became organized in longitudinal bundles from P16 onwards. The relatively late appearance of dendrite bundles in the soleus motoneuron pool suggests that they might be related to the fine-tuning of neuronal activity rather than patterning of motor activity. The occurrence of dendrite bundles in SOL and not in TA motoneuron pools suggests that they may be related to the different afferent organization of this postural muscle or to its tonic activation pattern. PMID- 1602052 TI - Embryonic development of a population of spiking local interneurones in the locust (Schistocerca gregaria). AB - We examined the embryonic development of an identified group of thoracic spiking local interneurones in the locust. These interneurones are primary integrators of mechanosensory information from the legs and make inhibitory output connections with motor neurones, nonspiking local interneurones, and intersegmental interneurones. Using intracellular dye injection, we traced the origins of these interneurones and described their morphological development. All of the interneurones in this population are produced by neuroblast NB4-1. The interneurones are produced during the latter stages of the neuroblast lineage and could not be identified before 55% development. Their growth could be divided into three distinct phases: first, a period of initial outgrowth (55-70%) during which the basic skeleton of major neurites is formed; second, a shorter period of rapid growth (70-80%) during which the basic skeleton is elaborated by the addition of many side branches; and third, a period of maturation (80-95%) during which the branches formed during earlier growth appear to be pruned. The possible implications of these results for neural development and synaptogenesis are discussed. PMID- 1602053 TI - The localization of nerve growth factor-like immunoreactivity in the adult rat basal forebrain and hippocampal formation. AB - The role of nerve growth factor (NGF) as a target derived neurotrophic agent for specific cell populations in the peripheral nervous system has been well documented and much evidence suggests that NGF may serve a similar neurotrophic role in the CNS supporting the cholinergic neurons of the basal forebrain. Previous attempts to localize NGF by immunocytochemical methods, however, have not yielded evidence confirming the regional distribution expected based upon reported levels of extractable NGF. In the present study, affinity purified polyclonal antibodies to beta-NGF and a modified immunohistochemical protocol were used to demonstrate specific NGF-like immunoreactivity in the adult rat hippocampal formation and basal forebrain. In the hippocampal formation, NGF-like immunoreactivity was localized primarily within the hilus of the dentate gyrus and within stratum lucidum of the CA3 and CA2 hippocampal subfields. Staining appeared to be associated with cell processes and was similar to the reported distribution of mossy fibers suggesting that granule cells may either serve as a primary source of hippocampal NGF or that mossy fibers selectively accumulate NGF produced by other cell populations. In the basal forebrain, NGF-like immunoreactivity was localized within neuronal cell bodies of the medial septum, diagonal band, and nucleus basalis of Meynert and was further demonstrated to colocalize exclusively with LNGF-R positive neurons. These findings demonstrate the presence of an NGF-like antigen in association with cholinergic neurons of the basal forebrain and strongly support the hypothesis that NGF may serve as an endogenous trophic factor for this adult neuronal population. PMID- 1602054 TI - Pathology of the mucous coat of trout skin during an erosive bacterial dermatitis: a technical advance in mucous coat stabilization for ultrastructural examination. AB - A fixation regime which combined cryopreservation, freeze drying and vapour fixation with osmium tetroxide, was found to preserve the mucous coat of trout skin for ambient temperature scanning electron microscopy. The regime was used to study changes to the mucous coat of trout skin during a spontaneous outbreak of "columnaris" disease--a common dermatitis of commercial salmonids associated with the bacterial pathogen Cytophaga columnaris. Infected and damaged regions of skin were covered by a mucous coat which differed from that which covered adjacent unaffected areas. In unaffected areas, the mucous coat topography was smooth and relatively featureless. In contrast, the mucous coat which covered damaged areas was fissured, cratered and contained exfoliated epithelial cells. Nevertheless, this study showed that even sites of extensive dermal ulceration, in which mucous cells had been destroyed, retained a partial mucous coat. This suggests that mucus, after secretion, flows over the skin surface, rather than functioning only near the site of production. Because of the various protective functions attributed to the mucous coat, its partial presence over areas of skin damage would contribute to defence against secondary pathogens and to the prevention of excess movement of ions and water at these sites. The technical development in mucous stabilization, described in this paper, will provide a means for examining morphological changes to the mucous coat of fish skin in response to a range of stimuli in future studies. PMID- 1602055 TI - Immunohistochemical identification of ferritin, lactoferrin and transferrin in leprosy lesions of human skin biopsies. AB - Granulomatous lesions of human leprosy contained ferritin and lactoferrin but little or no transferrin, as demonstrated by the avidin-biotin complex immunoperoxidase method. Lactoferrin was found in the neutrophils. These results suggested that the cells of the host mononuclear phagocyte system in leprosy granulomas provide an adequate nutritional environment for iron acquisition by M. leprae. A possible role of iron binding proteins in the granulomas is discussed in relation to previous data on bovine paratuberculous granulomas. PMID- 1602056 TI - The effect of inoculation of Pasteurella haemolytica into the lactating mammary gland of mice, rats, rabbits, sows and cows. AB - An isolate of Pasteurella haemolytica (A9), which consistently produced severe mastitis in ewes, was inoculated into the lactating mammary glands of a variety of species. Mastitis did not develop after the inoculation of log-phase bacteria into the mammary gland of lactating mice, rats, rabbits or sows but did so in the mammary gland of two cows. Another A9 isolate from a ewe with mastitis and an A1 isolate from a bovine pneumonic lung also induced mastitis in cows. Thus, in this study, P. haemolytica produced mastitis only in ruminant animals. PMID- 1602057 TI - Development and immunophenotyping of the pharyngeal tonsil (adenoid) in cattle. AB - Immunoperoxidase staining and electron and light microscopy were used to characterize the development of the pharyngeal tonsil in 98 cattle aged between 30 days of gestation and 12 years. The rugae of the pharyngeal tonsil were poorly formed before 95 days of gestation. Microvillous (M) cells associated with intra epithelial leucocytes (lympho-epithelium) were scattered among ciliated and goblet cells covering most of the surface in post-natal animals. Intra-epithelial leucocytes were rare in fetuses, but ciliated and M cells could be distinguished. Leucocytes of the lamina propria started to accumulate at approximately 120 days of gestation. A loose accumulation of mononuclear cells progressed into a B-cell rich upper and T-cell rich lower layer, with typical lymphoid tissue organization in post-natal animals and lymphoid involution in aged cattle. Primary lymphoid follicles formed at 5 months of gestation, but germinal centres did not form until 2 to 4 weeks after birth. Except for null cells, the relative number of cells staining for each leucocyte phenotype or MHC class II antigen increased with age, especially during the neonatal period. The early development, strategic location and specialized structure of the pharyngeal tonsil suggest an important role in modulating inhaled antigens in cattle. Fetal and neonatal calves had minimal lymphoid tissue priming, as indicated by lack of secondary follicles, low MHC class II expression and few intra-epithelial leucocytes. The phenotypic differences may be relevant to the increased susceptibility of calves to infectious diseases shortly after birth. PMID- 1602058 TI - Bovine herpesvirus-1-induced pharyngeal tonsil lesions in neonatal and weanling calves. AB - The potential involvement of the pharyngeal tonsil in the pathogenesis of bovine herpesvirus-1 (BHV-1) infection was examined in neonatal and weanling calves infected by intranasal aerosol. Calves were monitored from days 1 to 5, and on day 6 (neonates) or 8 (weanlings) and, in a second trial at day 4.5, by histology, electron microscopy, immunocytochemistry and virus isolation. Mucosal lesions of neonates were similar to, but less extensive than, those of weanling calves. Loss of microvilli and goblet cells, with minimal epithelial erosions as early as day 1, progressed to necrosis of epithelium and adjacent lymphoid tissue, and leucocyte exudation. Lesions and clinical disease were progressive up to and including day 6 in neonates, but resolving in weanlings on days 5 and 8. By transmission electron microscopy, the physical characteristics of the phagocytic cells appeared similar in both age groups, and viral replication was not identified in leucocytes. Virus was isolated from, or found by immunocytochemistry in, the pharyngeal tonsil of all calves examined, except for two weanlings on days 1 and 8. Virus as detected by immunocytochemistry was restricted to epithelium and superficial lymphoid tissue in neonates, but was found in deep lymphoid tissue around germinal centres in weanlings. The study showed that the pharyngeal tonsil is readily infected with BHV-1 and may be an important lymphoid tissue for early anti-viral responses. The delayed inflammatory response and reduced viral clearance may contribute to the increased susceptibility of neonatal calves to fatal BHV-1 infections. PMID- 1602059 TI - Responses of mucus-producing cells in gill disease of rainbow trout (Oncorhynchus mykiss). AB - This paper documents the responses of mucus-producing cells in the gills of rainbow trout (Oncorhynchus mykiss) throughout a naturally occurring outbreak of bacterial gill disease (BGD) and following exposure to experimentally induced high concentrations of ammonia and suspended solids. The responses were examined at three sites on the gill filament with three histochemical stains selected to identify the main types of mucous glycoproteins; these were periodic acid-Schiff (PAS), alcian blue pH 2.5 (AB2) and alcian blue pH 1.0 (AB1). In the BGD-infected fish, there was an increase in the numbers of PAS-positive and AB2-positive mucous cells and a corresponding decrease in AB1-positive cells. The greatest increase in mucus-producing cells occurred at the tips of the filaments, but the greatest relative change occurred at the mid-filamental (inter-lamellar) position. Fish exposed to high ammonia concentrations also had elevated numbers of mucus-producing cells, but there was no statistically significant change in fish exposed to high amounts of kaolin. The possible implications of these findings are discussed. PMID- 1602060 TI - Sulphide-induced polioencephalomalacia in lambs. AB - Polioencephalomalacia (PEM) was induced in four of 10 lambs by the administration of a sulphide solution into the oesophagus at 20 min intervals for a period of 40 to 120 min. Signs of neurological dysfunction occurred in all 10 lambs during that time and included stupor, visual impairment and seizures. Gross autofluorescent and microscopic lesions in cerebrocortical grey matter were present as soon as 20 h after sulphide administration and were indistinguishable from lesions in naturally occurring disease. These findings, when considered together with an earlier study that revealed an association between high ruminal concentrations of sulphide and PEM, indicate that this disease can result from sulphide toxicosis, independent of the metabolic status of thiamine. PMID- 1602061 TI - Inter- and intraspecific placentae in sheep, goats and sheep-goat chimaeras. AB - These studies compared inter- and intraspecific placentae during implantation and at full-term in sheep, goats and interspecific sheep-goat chimaeras. Histological sections prepared from intra- and interspecific day-26, 32 and 36 placentae in ewes and does indicated an altered ability of the trophoblast to invade the maternal caruncle in interspecific pregnancies. Two sheep-in-goat pregnancies were less, and two goat-in-sheep pregnancies were more, invasive than homologous pregnancies. Caprine pregnancies in chimaeras generally terminated before timed samples could be obtained, but biopsy samples collected at laparotomy between days 42 and 48 demonstrated both normal and abnormal placentation in chimaeras after breedings to rams. In six of 11 full-term fetal placentae from ovine pregnancies in chimaeras, there was abnormal retention of maternal caruncular tissue to the extent that macroscopic lesions were visible on the surface of the fetal cotyledons. Histological observations indicated that proliferation of maternal septa and hyalinization of maternal vessels had occurred at the expense of the fetal villi. Overall, the results suggested that the physiological events that regulate implantation are different in the two species, despite anatomical similarities between the ovine and caprine placenta. The caprine conceptus is likely to be rejected in the ovine or chimaeric uterus because of its over invasiveness in the early stages of implantation, whereas the ovine conceptus can survive in the potentially chimaeric uterus. PMID- 1602062 TI - Pathology of experimental Trypanosoma evansi infection in rabbits. AB - Histopathological examination of tissue sections from the organs of rabbits experimentally infected with Trypanosoma evansi revealed evidence of a vigorous immunological response. Changes in the spleen, lymph nodes, vulva, eyelids and ears indicated a protective immune response, but changes in the kidneys, lungs and heart were destructive in nature and capable of causing sudden death of the host. Hepatic damage capable of interfering with the host's immune response was also observed. The presence of many parasites in the vulval tissue calls for further investigation into the possibility of sexual transmission of T. evansi. PMID- 1602063 TI - Malignant schwannoma arising from the trigeminal nerve in a rat. PMID- 1602064 TI - Cytogenetic studies in a canine malignant melanoma. AB - In a 13-year-old, male rough-haired Dachshund with a malignant melanoma, cytogenetic evaluation of tumour cells showed hyperdiploidy (79 to 81 chromosomes) in 50 per cent of the metaphases. Several bi-armed chromosomes (centric fusions, one isochromosome and two unidentified markers) were observed. PMID- 1602065 TI - Authority, leadership and management in nursing. PMID- 1602066 TI - Compliance of young diabetics with health regimens. AB - The compliance of young patients with diabetes regimens is explored by means of a questionnaire filled in by both the patients and their nurses and compared with the patients' glycosylated haemoglobin (HBA1) levels. The structured questionnaire was completed by 47 diabetics aged between 15 and 17 years. The adolescents had very similar views to the specialist nurse on their compliance with health regimens, and these assessments were also in line with the HBA1 values. One-third of the young patients showed a high degree of compliance with diabetes regimens, while just under a half showed average compliance; the remainder failed to comply adequately. Compliance was highest in the case of insulin treatment, self-care and co-operation with the nursing staff, and poorest in following dietary and home monitoring instructions. PMID- 1602067 TI - The family, crisis and chronic illness: an evolutionary model. AB - While chronic illness has a profound impact upon the individual, an immense burden is imposed upon the family. When the competing demands of an illness and the family escalate exponentially, there may be a crisis. Traditionally, crisis theory has been applied to acute care contexts such as emergency, intensive care and mental health nursing. Yet, clinical experience with families and chronic illness supports the notion of periodic crises from the prediagnostic phase to the long-haul of the illness. Moreover, the authors hypothesize that the family's perception of the event determines whether the crisis is perceived as a threat or a challenge. This paper thus addresses the perception of crisis within the framework of chronic illness from a biological and family systems nursing perspective. First, the theory of Humberto Maturana, a Chilean biologist, is explored and applied to clinical observations regarding family, crisis and chronic illness. Second, an evolutionary model for conceptualizing crisis and chronic illness is presented. Third, the role of beliefs in the family perceptions of crisis and chronic illness is discussed. PMID- 1602068 TI - A behavioural modelling approach to curriculum development and evaluation of health promotion for nurses. AB - This paper outlines the way in which two behavioural science models may be used in the processes of curriculum development and course evaluation. The models are the stress-coping paradigm associated with the work of Lazarus and the theory of self and identity developed from the work of Mead. It is suggested that a clear articulation of the underlying behavioural processes is fundamental in course design and appraisal. PMID- 1602069 TI - Staff anxieties about death in residential settings for elderly people. AB - This study examined the relationship between death anxiety, the anxiety surrounding dealing practically with dying, and the level of experience of care assistants in residential settings for the elderly. It also examined the perception of the officer in charge of the establishment of the care assistants' level of anxiety. Age was the best predictor of both death anxiety and practical anxiety, the two being correlated. There was also a difference in perception of staff anxiety as a consequence of ethnic-group membership. The implications of this for training and practice are discussed. PMID- 1602070 TI - Non-attendance at out-patient clinics: a case study. AB - Non-attendance at out-patient clinics is a persistent, worldwide problem. In contrast with previous research, a qualitative approach was used in this study to examine reasons for non-attendance at out-patient clinics in one Belfast hospital, by exploring perspectives of general practitioners (GPs), hospital staff and defaulters. Findings revealed conflicts of opinion between GPs and hospital staff on appropriate management of certain medical and postnatal patients. Patients' reasons for defaulting were wide-ranging; however, 32% of those interviewed did not attend, or were recorded as non-attenders, for reasons relating to inefficient hospital administration. It is concluded that the causes of non-attendance were multifactorial, and non-attenders could not be stereotyped as irresponsible. Suggested measures to alleviate the problem include discussion between groups of professionals on responsibility for care of medical and postnatal patients, increased negotiation between patients and physicians in order to develop agreed programmes of care, and, where possible, a shifting of the onus of responsibility for making and cancelling appointments onto patients. PMID- 1602071 TI - Assessing the outcomes of nursing care. AB - There are many dimensions to outcome measurement for patient care and this study focuses on one aspect of outcome, namely that which is most concerned with the immediate effects of nursing care. Traditionally, outcome studies have been almost exclusively concerned with measuring the clinical outcomes of care with very little attempt being made to assess the effect of the nurses' contributions to that care. One of this study's purposes has been to redress this imbalance. As part of a research project on skill mix and the effectiveness of nursing care, a number of patient-focused standards related to the outcome of nursing care were designed. These were tested, in a case study situation, on 15 wards at seven acute hospitals. Initial testing indicates that these outcome measures show promise as a valid and reliable evaluation instrument with the utility for easy application in the clinical setting. They are being presented as a possible way forward to assessing the outcomes of nursing care. PMID- 1602072 TI - AIDS, nursing and occupational risk: an ethical analysis. AB - This paper examines the notion of risk assessment in relation to nursing patients with HIV infection or AIDS. Risk assessment consists in examining three features of a given hazard; its magnitude, its probability, and its acceptability. In relation to the last of these, an 'acceptability threshold' can be identified. If contact with HIV-infected patients is perceived to pass this threshold, nurses may seek to abrogate the usual 'duty to treat'. Rather than endeavour to pinpoint this threshold, the paper explores some of the factors which may either raise or lower it, and their ethical implications. In particular, the consequences of setting a high threshold, and thereby limiting or avoiding contact with patients infected with HIV, are examined. In this debate, the burden of proof is seen as resting firmly on nurses themselves, not on the patients at risk of being deprived of care. PMID- 1602073 TI - The telephone survey: a methodological strategy for obtaining information. AB - Studies have shown that students and the general population have little knowledge about nursing schools and the nursing profession. This study investigates the extent to which a sample of the population of Brazil is aware of the existence of nursing schools, and how they have obtained this information. Data were collected by telephone interviews. The sample consisted of 326 subjects whose telephone numbers were taken from the telephone book. Analysis showed that 73% of the subjects were aware of the existence of two nursing schools in the city; however, 65.03% did not know the names of these schools. Direct communication with friends and family, as well as indirect communication by television and advertising, were the sources of information mentioned by those questioned. PMID- 1602074 TI - Consequences of the division of nursing labour for elderly patients in a continuing care setting. AB - Detailed analysis of nursing activity has suggested that unqualified nursing auxiliaries provide most of the direct patient care and one-to-one contact for elderly patients requiring continuing care. In order to investigate the effects of this division of labour on the quality of care received, a comparison of the content of nurses' verbal interaction with patients was made between qualified and unqualified staff. Content analysis of tape-recorded nurse-patient interaction revealed recurring types of nurse verbal behaviour and a framework for examining similarities/differences between qualified and unqualified staff was developed. Frequency counts for individual verbal behaviour types suggest some differences between staff grades, particularly in relation to verbal behaviours which attempt to increase the patients' control over their activities and environment. The difficulty of assessing the implications of the differential use of particular verbal strategies is discussed in relation to the absence of evidence to confirm patient outcomes in relation to different verbal techniques. Further research in this area is required. PMID- 1602075 TI - Developing Flanagan's critical incident technique to elicit indicators of high and low quality nursing care from patients and their nurses. AB - This paper discusses a development of Flanagan's critical incident technique (CIT) to elicit indicators of high and low quality nursing from patients and their nurses on medical, surgical and elderly care wards. Stages in undertaking the CIT are identified and presuppositions held by most researchers about the nature of the technique are identified. The paper describes how the authors moved to a different set of presuppositions during the course of the study. Preliminary analysis of interview transcripts revealed that critical incidents need not always be demarcated scenes with a clear beginning and end, but may arise from respondents summarizing their overall experience within their description of one incident. Characteristically respondents were unable to give a detailed account of such incidents but validity may be established by the fact that respondents appear to recount what actually happened as they saw it, and what they said was clearly important to them. The researchers found that the most appropriate basic unit of analysis was not the incident itself but 'happenings' revealed by incidents that are 'critical' by virtue of being important to respondents with respect to the quality of nursing care. The importance of CIT researchers achieving an understanding of the 'meaning' of critical happenings to respondents is emphasized. Analysis of the interview transcripts is facilitated by the use of INGRES, a relational database computer program which should enable a 'personal theory' of quality nursing for each respondent, both patients and nurses, to be described. The study suggests that the CIT is a flexible technique which may be adapted to meet the demands of nursing research. If carefully applied, the CIT seems capable of capitalizing on respondents' own stories and avoids the loss of information which occurs when complex narratives are reduced to simple descriptive categories. Patients and nurses have unique perspectives on nursing and their views are of primary importance in understanding what quality means with respect to the interpersonal processes that are integral to nursing care. This paper discusses the identification of indicators of quality nursing from interviews with patients and nurses using the authors' development of Flanagan's critical incident technique. PMID- 1602076 TI - King and Neuman: in search of the nursing paradigm. AB - There is a wellspring of support within the nursing profession for the development of a true nursing paradigm, based on a unified theory to support practice, to advance the professional status of nursing in a changing health care environment. In this, the preparadigm stage of nursing, there are at least 125 theories, many of them viable. Prominent among them are those of King and Neuman. The King theory is rooted in the effectiveness of human interaction between nurse and patient to set and achieve health goals. The Neuman theory is a stress oriented system espousing the development of patient defences and resistance. The similarities outnumber the differences between the two. Both seek a conceptual foundation upon which the profession may be structured to achieve its highest ideals. PMID- 1602077 TI - Using repertory grid research methodology in nurse education and practice: a critique. AB - This paper defines and describes the repertory grid technique and critically evaluates its potential as an effective research tool in nurse education and practice. Discussion includes a focus on both the merits and limitations of the technique, and suggestions for curriculum development in nurse education are put forward. PMID- 1602078 TI - Empowerment in nursing education: concept analysis and application to philosophy, learning and instruction. AB - The Walker & Avant strategy is used to complete a concept analysis of empowerment. Empowerment is defined as the interpersonal process of providing the proper tools, resources and environment to build, develop and increase the ability and effectiveness of others to set and reach goals for individual and social ends. Empowerment occurs between two or more people: the person who empowers and the person(s) who is (are) empowered. The Murrell-Armstrong Empowerment matrix, with six categories of empowering behaviours, provides the theoretical framework. References from organizational, nursing, educational and sociological literature provide support for the defining attributes, antecedents and consequences of empowerment. A conceptual map depicts these relationships and demonstration cases serve to make the ideas more apparent. The concept of empowerment is applied to philosophy, learning and instruction. Pragmatism reflects the ideas presented on empowerment because both embrace individual and social goals, the student is active in the learning process, learning is lifelong, and the appropriate environment, tools and resources for learning must be present. Kolb's experimental learning model corresponds with empowerment and pragmatism. The works of Dewey, Lewin, Piaget, Rogers and Freire are used as the basis for the model. Kolb describes learning as a four-step process that includes concrete experience, reflective observation, abstract conceptualization and active experimentation. Transformative instruction is based on Freire's critical pedagogy, Belenky et al.'s connected teaching, Schon's reflection-in-action, and activities that allow students to complete the experimental learning cycle. Several strategies that promote transformative instruction are discussed. PMID- 1602079 TI - The quality of nurse education in the 1980s. AB - This paper describes a research project which attempted to evaluate the preregistration preparation of nurses as an educational pursuit. It argues that two major learning paradigms exist, education and training. These paradigms can be differentiated on the basis of three critical aspects of the curriculum which also indicate the key areas for quality assurance. These aspects are; the purposes of learning, the extant forms of knowledge and the nature of teacher student relationships. The paper describes a structural analysis of previous research on nurse education in the United Kingdom, and a student nurse opinion survey which aimed to identify those aspects of their course which were of most significance to student nurses. It was concluded that the preregistration preparation of nurses subsumed under a training paradigm and that the major determinant of this was the practice setting. There was also some indication that the nursing curriculum was not patient-centred and that the training paradigm did not encourage personal development in critical thinking, self-reliance and problem solving. The final part of the paper describes an experiment which attempted to demonstrate a link between practice teacher-student relationships and practitioner competence utilizing video presentation of 'teacher' behaviours and a patient-centredness measuring instrument. The experiment supported this link. In conclusion, it is argued that if UKCC Project 2000 is to avoid a replication of the past then educational development must be focused on the practicum and not just on forging links with higher education if a professional nurse education is to be achieved. PMID- 1602080 TI - Impact of nursing learning environments on adaptive competency development in baccalaureate nursing students. AB - Kolb's experiential learning theory (ELT) was used as a framework to study 179 generic baccalaureate students' perceptions of the contributions of different types of nursing learning environments to development of adaptive competencies described in the theory. In addition, students in each of the 4 years of the program were asked to describe their perceptions of the importance of Kolb's adaptive competencies for successful functioning in nursing settings as well as to rate their personal levels of skill on each competency. Nursing learning environments were thought to contribute most to divergent and convergent competencies, reflecting the importance of both people-oriented and scientific skills in nursing. Clinical experiences and the senior preceptorship experience contributed significantly more to the development of these competencies than typical nursing classes and nonnursing classes. Students considered assimilative competencies--such as testing theories--and ideas and accommodative competencies- such as leading and influencing others--relatively unimportant to successful functioning in nursing learning environments. Implications for nursing education are discussed. PMID- 1602081 TI - Experiences of nurse-researchers in gaining access to subjects for clinical nursing research. AB - This study investigated the experiences of nurse researchers in gaining access to potential research subjects within health care agencies. Responders were nurse researchers who were primary authors of clinical nursing research studies that had been published in nursing research journals between the years 1985 and 1989. A survey was mailed to 211 responders and returned by 99 (47 per cent). Eighty six were employed primarily by educational institutions. Responses to the survey indicated that these nurse researchers experienced political and procedural obstacles in gaining access to potential research subjects within health care agencies. PMID- 1602082 TI - Nurses and smoking: review and implications. AB - An analysis of smoking behavior among nurses shows unacceptably high levels of smoking, despite some evidence of a downward trend. In this article, the nature of tobacco dependence is examined, and an extensive review of demographic and causative factors associated with the smoking behavior of nurses is presented. The impact of smoking on the practice of nurses, particularly related to their ability to serve as health educators and role models, is critically examined. Areas for potential research and inquiry, along with some overall strategies for intervention, are identified. PMID- 1602083 TI - Beliefs of a nurse academician. PMID- 1602084 TI - Why cross-training won't work. PMID- 1602085 TI - Areas of outcome research for nursing. PMID- 1602086 TI - Total quality management--a new culture. PMID- 1602087 TI - Retrospective analysis of guardians' perceptions of cognitively impaired elderly. AB - The increased number of elderly persons who will become cognitively impaired in the near future is a cause for concern to all in the health care professions. Even though the final determination of incapacity and incompetency is a legal decision, input from health care professionals is weighed heavily by courts. Health professionals can have influence at the clinical level and also at the level of influencing social policy. Nurses rely on input from the assessments of informal caregivers. This research was conducted to determine guardians' perceptions of important criteria on the Incompetency Assessment Scale. Eleven guardians, a majority of whom were daughters of the elderly wards, perceived 9 of the 22 criteria on the IAS as important or very important to the question of incompetency. All nine criteria are found in Minnesota's statutory definition of incompetency, and also appear in the first two levels of the Maslow hierarchy of needs. Further research is recommended to develop a weighting or clustering of criteria to more accurately ascertain the way that incompetency judgments are made by guardians and other caregivers. PMID- 1602088 TI - Nursing competence in adolescent health: anticipating the future needs of youth. AB - The health problems of youth have dramatically shifted in the last 30 years from biological to social causes of morbidity and mortality. To assess the adequacy of nurses' knowledge and skills in adolescent health, a national survey of 445 nurses, including members of the American Public Health Association, the American School Health Association, and the National Association of Pediatric Nurse Associates and Practitioners, was undertaken in 1985. Results indicated that even among nurses who work with young people the most, areas of greatest knowledge and skill deficiencies included common social morbidities of adolescents. In addition to self-assessed inadequacies in knowledge and skills, nurses identified excessive time demands as a primary obstacle to the provision of health services to adolescents. To assure adequate preparation of nurses, it is recommended that accreditation criteria for baccalaureate and graduate programs specify essential adolescent health content for curricula compared to current accreditation criteria that generalizes "across the life span." Focusing on the enhancement of educational opportunities in adolescent health, nurses identified strategies for further education that would bridge the gap between the health needs of youth and nurse's self-perceived competencies in providing these services. PMID- 1602089 TI - Professionalism versus general critical thinking abilities of senior nursing students in four types of nursing curricula. AB - This descriptive study was undertaken to investigate the relationship between professionalism and critical thinking abilities of senior nursing students in four types of nursing educational programs: generic baccalaureate, associate, and diploma--the basic registered nurse (RN) programs--along with the upper division baccalaureate, specifically RN completion, program. Fifty students from each type of program were conveniently selected during the same spring semester before graduation. Professionalism was measured by the Health Care Professional Attitude Inventory; general critical thinking abilities, by the Watson-Glaser Critical Thinking Appraisal. For individual programs, low to moderate correlations ranging from r = 0.263 (diploma) to 0.516 (upper division) were found between critical thinking and professionalism. This culminated in a significant, low positive correlation (r = 0.447) between critical thinking and professionalism across all programs. Upper division seniors showed significant low to moderate positive correlations for age with critical thinking (r = 0.487) and professionalism (r = 0.327) that were not observed in the other programs. Comparisons of professionalism scores among programs showed that upper division seniors scored highest. The measure of professionalism for seniors from 4-year generic programs was not significantly different from associate degree seniors. Diploma program seniors showed the lowest level of professionalism. When critical thinking abilities were compared, seniors from generic and upper division baccalaureate programs showed significantly higher levels than those from associate and diploma programs. PMID- 1602090 TI - Faculty work load formulas in nursing education: a critical theory perspective. AB - The purpose of this article is to increase faculty awareness and understanding of the constraints and contradictions that are embedded within faculty work load formulas. An overview of critical social theory is presented and serves as a framework for the analysis of work load formulas within the context of their historical development and current usage. The ideologies, constraints, and interests of such formulas are identified and explored. Challenges exist to beliefs that faculty work load formulas are a just and equitable way to determine faculty responsibilities; that faculty worth can be objectified, categorized, quantified, and measured; and that the institutional norms and values of higher education are right for nursing. The feminist PEACE (praxis, empowerment, awareness, consensus, and evolvement) process, as developed by Wheeler and Chinn, is discussed and serves as a framework for the development of alternative methods to create autonomy, responsibility, and greater communication in establishing faculty work loads. The authors believe that only through awareness, reflection, understanding, and action can the tensions that create conflict and perpetuate dominance and authority be changed. PMID- 1602091 TI - Getting the story straight: evaluating the test-retest reliability of a university health history questionnaire. AB - This study was designed to establish the reliability of a health history questionnaire used as a screening tool for incoming university students. The authors used a test-retest design, with a test interval of 6 months, on a sample of medical and nursing students. The analysis focused on overall reliability of the questionnaire and reproducibility of specific items, based on question format. Questionnaire items of specific interest were those with dichotomous yes/no response options versus open-ended format questions, those using the words frequently or recently, or those that asked multiple questions. Demographic characteristics of the subjects were considered in the evaluation of reliability. Overall reliability of the questionnaire (93.6%) was above the anticipated level of 90%, and subject sex or program of study did not show any significant differences in reproducibility of responses. Although wording of questions did not affect item reliability, dichotomous format questions demonstrated a higher degree of reliability (96.4%) than the overall reliability of the questionnaire. Recommendations for enhancing the reliability of the questionnaire are based on item analysis and information gathered from interviews with subjects. PMID- 1602092 TI - Predictors of safer sex on the college campus: a social cognitive theory analysis. AB - In April and May 1989, the authors surveyed a sample of students enrolled on four college campuses in New Jersey (N = 923) concerning their HIV transmission related behavior, knowledge, and a variety of conceptual variables taken primarily from social cognitive theory that were thought to be potentially predictive of safer sexual behavior. Analyses of sexually active, unmarried students' responses indicated that men expected more negative outcomes of condom use and were more likely to have sexual intercourse while under the influence of alcohol or other drugs, whereas women reported higher perceived self-efficacy to practice safer sex. Regression analyses indicated that, among the factors assessed, stronger perceptions of self-efficacy to engage in safer behavior, expecting fewer negative outcomes of condom use, and less frequency of sex in conjunction with alcohol or other drug use significantly predicted safer sexual behavior. Enhanced self-efficacy to discuss personal history with a new partner was associated with a greater number of risky encounters. Implications of these findings for intervention efforts with students are discussed. PMID- 1602093 TI - Relationship marketing and service quality. AB - The delivery of services in college health centers is improved through the use of relationship marketing and service quality advancement. Relationship marketing works to attract, maintain, and enhance customer or client relationships with the healthcare provider. The facets of relationship marketing are explored, with the greatest emphasis placed on internal marketing. Higher quality health services come from continuous improvement, a focus on process, and intensive staff development and participation, which build a service culture. PMID- 1602094 TI - Screening college students for hypercholesterolemia. AB - Selective screening for children and mass screening for adults are the two strategies for detecting hypercholesterolemia and identifying individuals at risk for early heart attacks that have been recommended by the American Academy of Pediatrics and the American Medical Association. The interval marking the end of childhood and the beginning of adulthood is a time of transition without an unwavering demarcation line. It is a time when many adult disorders that demand attention and detection begin. Because of the close relationship of elevated cholesterol levels in youth to subsequent cardiovascular disease, a small liberal arts university began mandatory mass cholesterol screening for all full- or part time students who matriculated in September 1977. More than thirty 18- and 19 year-old first-year students with unknown hypercholesterolemia were detected each year. The mean cost per case identified is estimated to have been $212. The author concluded that mass screening of students entering college can identify, at a reasonable cost, students who have high levels of cholesterol. PMID- 1602095 TI - Cholesterol screening--what should we be doing? PMID- 1602096 TI - One university's use of volunteer mental health professionals. AB - The Homewood campus of The Johns Hopkins University in Baltimore has been served by volunteer mental health professionals--psychiatric residents, psychologists, social workers, psychiatric nurses, and counselors--over a 17-year period. The nonsalaried associates have donated an estimated $3 million in professional services (based on prevailing rates for therapy) and served a yearly caseload varying from 293 in 1973 to more than 500 in the years since 1978. The author offers suggestions for others who would like to beat the financial crunch by using trained volunteers. PMID- 1602098 TI - College health 2050. AB - On May 31, 2040, Kunta Kinte Sanchez O'Shaunessey-Chan, MOND, president of the North American College Health Association (NACHA), gave the keynote address at the opening session of the annual meeting held in the Marriott Conference Center, Saskatoon, Saskatchewan. He recounted important events of the past 50 years that have shaped the college health field of today, and he predicted important trends for the next decade. Although his speech was given in Spanish, it was simultaneously translated into English, French, and 15 other languages requested by attendees. The English version follows. PMID- 1602097 TI - Liquid nitrogen treatment of hand and plantar warts. AB - The author reports on a study of the liquid nitrogen treatment of warts at the Rutgers University Student Health Center. He demonstrates that liquid nitrogen therapy is a safe, effective treatment method, appropriate for use by nurses and other primary providers in a college health setting. PMID- 1602099 TI - College health services should promote good Samaritan rules as part of university alcohol policies. AB - When a student or organization assists an intoxicated individual in procuring Safety and Security, local or state police, and/or professional medical assistance, neither the intoxicated individual, if a Dartmouth student, nor the individual or group who assists will be subject to formal College disciplinary action for (1) being intoxicated, or (2) having provided that person alcohol. This refers to isolated incidents only and does not excuse or protect those who flagrantly or repeatedly violate the College Alcohol Policy. PMID- 1602101 TI - [Leber's optic neuropathy: new diagnostic prospects]. AB - The diagnosis of Leber's hereditary optic neuropathy, essentially based on a family history of a similar illness, becomes difficult in sporadic cases. In this disease, mitochondrial DNA mutations have been recently discovered and detected by digestion with restriction enzyme after amplification by the Polymerase Chain Reaction. We present two patients in whom these molecular biological techniques confirmed the diagnosis of Leber's hereditary optic neuropathy in the absence of a convincing family history. These new molecular biological methods, providing a precious diagnostic test, would certainly play a greater part in genetic counselling and would probably be a prerequisite for the development of new forms of therapy. PMID- 1602100 TI - [Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study]. AB - A multicentre study of a new preparation of povidone iodine (5% betadine) was carried out on 150 patients undergoing cataract surgery. Pre-operatively the eye was prepared by daubing the peri-ocular skin and a two-minute instillation into the conjunctival fornices. No other antiseptic was applied. Tolerance to the product was evaluated in all the patients: clinical evaluation postoperatively and during a 60-day follow-up period confirmed that the preparation was harmless to the eye. Microbiological investigations (comprising conjunctival swabbing, bacterial culture and count of the bacterial species isolated, before and after application of the product) performed on 60 patients showed a significant fall in the number of colonies after treatment. PMID- 1602102 TI - [Canalicular stenoses complicating the insertion of lacrimal plugs. Incidence and mechanisms]. AB - Changes in canalicular permeability following the insertion of punctum plugs was studied. This occlusive method was used to treat dry eye syndrome in 43 patients over a period of 32 months. All had normal canalicular patency, confirmed on the day of implantation. One hundred and five large plugs were used (2.4 plugs per patient). Twenty seven (25.7%) impassable acquired canalicular stenoses were seen in 15 patients. The canalicular site of the 27 stenoses was the same: junction between the vertical and horizontal portions. Among the 27 stenoses: 4 plugs had disappeared at an unknown time, with follow-up probing taking place after a mean interval of 7.5 (months range: 1 to 15 months); 17 plugs had been expelled after being in place for an average of 5 months (range: 1 to 12 months; standard deviation 3.47), with follow-up examination taking place on average 12 months after insertion (range: 6 to 17 months; standard deviation 3.4); and 6 plugs were still in place after a mean of 7 months (range: 2 to 15 months; standard deviation 4.73) and the stenosis was discovered when they were removed. They were intact. These 6 Cases eliminate any possibility of intra-canalicular migration of the prosthesis--of all or part--of the prosthesis. Stenoses appeared to develop rapidly: 45% of cases were discovered during the first 3 months. 16/27 (59%) of stenoses were investigated a second time, 6 months later on average (range: 2 to 12 months): these 16 canaliculi all remained impassable. PMID- 1602103 TI - [An uncommon case of central retinal artery occlusion]. PMID- 1602104 TI - [Diagnosis by Doppler color echography of dural carotid-cavernous fistula of ophthalmological manifestation]. AB - The case reported here, concerns a spontaneous low-flow fistula between the external carotid arterial network and the cavernous sinus, with ophthalmological symptoms (exophthalmos, red eye) in an old woman with cardiac failure. The shunt was diagnosed by color-Doppler-imaging, which showed a flow reversal with a systolic component in the superior and inferior enlarged ophthalmic veins. This finding led the authors to extend the arterial filling sequence since the shunt was not detectable on standard arterial views. Embolization was performed during angiography which remains necessary to localize the shunt and to treat the fistula. The clinical symptoms progressively returned to normal and the correction of the hemodynamic disturbances could be followed by color-Doppler imaging, a non-invasive technique which can be easily repeated. PMID- 1602105 TI - [Malignant glaucoma (glaucoma caused by ciliary block)]. PMID- 1602106 TI - [Prevention of peroperative miosis: comparison between prostaglandin inhibitors. Sodium diclofenac and indomethacin in local application]. AB - Diclofenac sodium 0.1% (Voltaren) prevents surgically induced miosis during extracapsular cataract extraction in a more long lasting way than indomethacin 1% (Indocid). Just before the IOL-implantation, in eyes treated with diclofenac sodium eye drops, the apparent mean pupil size was constricted by approximately 1 mm less than in the control group (p.01). At the same critical moment, 50% of the pupils treated with diclofenac sodium and only 20% of the pupils in the control and indomethacin groups were larger than 6 mm. PMID- 1602107 TI - [Bilateral actinic keratosis of the corneal limbus. Apropos of a case]. AB - Keratinised tumors of the conjunctiva are not uncommon lesions. However, different pathological lesions may have a similar clinical. Actinic keratosis is one of these, it is an epithelial pre-cancerous lesion of the conjunctiva, which may become, if untreated, an invasive carcinoma. A case of bilateral lesions of this type is reported in a 61-year-old male patient who used to work outdoors, and the clinical diagnosis was followed by bilateral surgical removal of the two lesions. Histological examination study showed that the acquired modifications of the epithelium were typical of conjunctival actinic keratosis. PMID- 1602108 TI - [Capsulorhexis]. PMID- 1602109 TI - [Retinal detachment in pseudophakia. Analysis of 164 cases]. AB - The authors present a study of 164 pseudophakic retinal detachments followed up at least six months after surgery. All the parameters were statistically evaluated. It shows that preoperative general patterns are similar to those described previously. This study was mainly concerned with finding factors which might influence anatomical success. Only proliferative vitreo-retinopathy was statistically correlated with the quality of the results. In contrast, the demonstration and localisation of retinal tears, IOL design and even vitreous loss do not influence the prognosis. PMID- 1602110 TI - Clinical research with community-based older women. AB - Subjects for research with community-based elderly women are best obtained by first establishing rapport with the manager of the retirement home or apartment complex for the elderly. The site for group research should be comfortable, private, and free of distractions; it should also be centrally located and easily accessible for subjects with impaired mobility. Verbal instructions and printed questionnaires must be appropriate for the elderly subject's hearing, visual acuity, and reading level. It is important to ensure that subjects are using functional hearing aids and glasses, to allow extra time to repeat or explain questions, and to plan sessions that are not lengthy or tiring. PMID- 1602111 TI - Elder beliefs: blocks to pain management. AB - Elderly patients have beliefs that, if not incorporated into the pain assessment, can block pain management by interfering with the patient's willingness to acknowledge pain and provide complete and accurate information about the pain experience. Patient beliefs that can block pain management include beliefs about self-concept and the aging process; the patient role; health professionals; pain; and consequences of treatment, including addiction, xerostomia, falls, constipation, and sexual and personality problems. Optimal pain management in the elderly is based on a complete assessment of pain, which may take several patient nurse visits. Patients tend to reveal more information about health problems with succeeding visits, even if the patient is seen by a different person each time. PMID- 1602112 TI - Health and social support of elderly families in developed countries. Nurses must adapt a global perspective. AB - Although the majority of the elderly retain functions until later years, it is estimated that for each good functional year that is added to life, 3.5 compromised years are also added. The single most important thing that can be done to assist older persons and their families is education of the elder, the family, and the formal caregiver. Although nurses support including the patient in the decision making process, this is often not done when it comes to the individual practice situation. There is a need for more research in this area. The challenge for the nursing staff is to publish innovative programs so others can share in their experiences. Most often these novel interventions are lost because they are not published; they will have to be rediscovered. PMID- 1602113 TI - Gerontological nursing. The concept of comfort in an environmental framework. AB - The Facilitative Environment Framework organizes a holistic gerontological practice. Comfort describes the state of patients when their excess physiological and psychological needs have been met. Patients must be in a state of comfort before they can perform the tasks of optimum function. The Facilitative Environment Framework was applied to a dementia setting, but it is suitable for other gerontological settings as well. PMID- 1602115 TI - Confessions of a geriatric nurse researcher. PMID- 1602114 TI - Urinary incontinence: two viewpoints. PMID- 1602116 TI - Clinical considerations. Surrogate decision making for hospitalized elders. AB - Nurses are increasingly caring for older persons who have become decisionally incapacitated due to acute or chronic illnesses. A nurse may be called on to share in the decision-making process for the elderly patient or to assist in bringing about a surrogate decision involving the patient's relatives and the medical team. PMID- 1602117 TI - Practice parameters: how should we view them? PMID- 1602118 TI - Preventing bicycle deaths. PMID- 1602119 TI - Baby bottle tooth decay. PMID- 1602120 TI - Health commissioner concerned about access to care. Interview by Bob Carlson. PMID- 1602121 TI - Indiana chosen for pilot project in risk management. PMID- 1602122 TI - Medical teams praised for rescue efforts. PMID- 1602123 TI - Ethical issues in withholding and withdrawing life-sustaining treatment. PMID- 1602124 TI - Valuing a practice for purchase or sale. PMID- 1602125 TI - ISMA successful during 1992 legislative session. PMID- 1602126 TI - Delayed posttraumatic diaphragmatic hernia: case report and literature review. AB - The case of a 36-year-old man with an unsuspected delayed posttraumatic diaphragmatic hernia is described. This entity often presents with vague clinical symptoms and non-specific radiographic findings long after the initiating trauma has been forgotten. Therefore, the preoperative diagnosis of this entity is notoriously difficult, but failure to make this diagnosis carries a high mortality rate. A high index of suspicion must be maintained. PMID- 1602127 TI - Peptide and beta 2-microglobulin regulation of cell surface MHC class I conformation and expression. AB - We have examined the roles of peptide and beta 2-microglobulin (beta 2m) in regulating the conformation and expression level of class I molecules on the cell surface. Using a cell line synthesizing H-2Dd H chain and mouse beta 2m but defective in endogenous peptide loading, we demonstrate the ability of either exogenous peptide or beta 2m alone to increase surface H-2Dd expression at both 25 degrees C and 37 degrees C. Peptide and beta 2m show marked synergy in their abilities to increase surface class I expression, with minimal increases promoted by peptide in the absence of free beta 2m. Low temperature-induced molecules have indistinguishable rates of loss of beta 2m and alpha 1/alpha 2 domain conformational epitopes during culture at 37 degrees C. However, the rate of alpha 3 epitope loss is much slower, indicating a minimum of two steps in class I loss from the cell surface: 1) loss of beta 2m binding to H chain and unfolding of the alpha 1/alpha 2 region; then 2) denaturation, degradation, or internalization of the free H chains possessing alpha 3 epitopes. These data show for the first time that free H chains survive for a finite time on the membrane in a form capable of refolding into alpha 1/alpha 2 epitope positive molecules upon addition of beta 2m and peptide. This refolding in the presence of beta 2m and peptide can explain the reported requirement for both components in sensitizing cells for class I-dependent CTL lysis. It also indicates that such conformational changes in class I molecules are not strictly dependent on either newly synthesized H chains or on intracellular chaperons. The study of H chain peptide-beta 2m interaction on the cell surface may be relevant to understanding intracellular peptide loading events. PMID- 1602128 TI - A murine model of allergic bronchopulmonary aspergillosis with elevated eosinophils and IgE. AB - A model of allergic bronchopulmonary aspergillosis was developed by exposing BALB/c mice to Aspergillus fumigatus (AF) Ag. Animals immunized intranasally (i.n.) with soluble AF Ag produced low levels of serum IgE compared to animals given alum precipitated AF Ag i.p. The latter treatment also produced higher levels of serum IgG1 and AF-specific IgG1 than soluble AF given i.p. or i.n.. Blood and lung eosinophilia was detected in mice repeatedly exposed to AF by i.n. but not in the groups injected i.p. Particulate AF Ag-induced striking blood and lung eosinophilia and elevated levels of serum IgE in mice preexposed to AF Ag. The results indicate that route of inoculation and physical nature of Ag determine the immune response and can be manipulated to obtain enhanced IgE, eosinophils, or both in the animal model. PMID- 1602129 TI - Immunologic and hematologic effects of neuroendocrine hormones. Studies on DW/J dwarf mice. AB - DW/J dwarf mice lack acidophilic anterior pituitary cells and are deficient in growth hormone and other neuroendocrine mediators. These mice were examined to determine the effects of these deficiencies on hematopoietic and immune system development. Previous studies have suggested that these mice had immunologic defects primarily involving T cell development. However, we have found that these mice exhibit decreased peripheral blood cell counts affecting all lineages (erythrocytic, leukocytic, and platelets). Examination of lymphoid tissues of dwarf mice indicated that their spleens were hypoplastic. Treatment of these mice with recombinant human growth hormone resulted in a significant improvement of peripheral blood counts and spleen cell number. Analysis of the bone marrow indicated a profound deficiency of B cell progenitors in the dwarf mice. However, in untreated dwarf mice, mature B cells and T cells were observed in the spleens. Although treatment with recombinant human growth hormone could correct the hematopoietic deficiencies in these mice, it did not restore the B cell progenitor populations, suggesting that an absence of growth hormone is not solely responsible for this deficiency. Thus, these mice display significant myeloid and lymphoid deficiencies that have been previously undetected. PMID- 1602130 TI - In vivo deposition of myosin-specific autoantibodies in the hearts of mice with experimental autoimmune myocarditis. AB - Experimental autoimmune myocarditis (EAM) is elicited in certain strains of mice by immunizing with mouse cardiac myosin. Concomitant with the onset of myocardial inflammation is the induction of circulating IgG antibodies to myosin. To further examine the role of myosin in disease, both EAM-susceptible (A/J) and EAM resistant (B10.A) mice were immunized with myosin emulsified in CFA and examined for myocardial inflammation and IgG deposition. Myocarditis was common in susceptible, but not resistant strain mice. IgG deposition was extensive in A/J mice, but modest in B10.A mice, when compared to controls given adjuvant alone. Localization was independent of inflammatory or necrotic lesions. A spot ELISA indicated that antimyosin IgG antibody-secreting cells were present in the myocardial infiltrate and likely contributed to antibody localization. Antibody was eluted from the hearts of immunized animals and found to react strongly with normal heart tissue by indirect immunohistochemistry. This reactivity was not completely absorbed by skeletal muscle, indicating that some of the antibody was heart-specific. Western immunostaining demonstrated that eluates from immunized A/J and B10.A mice possessed anti-myosin antibody activity; similar reactivity was not observed in eluates from control mice of either strain. Comparison of heart reactivity with syngeneic and allogeneic tissue suggests that although myosin immunization elicits homologous antibody in both strains, each may recognize distinct epitopes. These findings strongly suggest that cardiac myosin or a myosin-like determinant is expressed on the surface of normal mouse myocytes. PMID- 1602131 TI - Effect of transforming growth factor (TGF)-beta 1 on IgA isotype expression. TGF beta 1 induces a small increase in sIgA+ B cells regardless of the method of B cell activation. AB - Transforming growth factor-beta (TGF-beta) has been reported to play an important role in IgA isotype expression when B cells are stimulated with LPS. The goal of the present study was to determine whether TGF-beta has similar effects on IgA isotype expression under more physiologic conditions utilizing a variety of B cell activation systems. As previously reported, in the LPS system TGF-beta caused a small, but significant, absolute increase in surface IgA (sIgA) expression and a very definite increase in IgA secretion; these effects were enhanced by IL-2 and IL-5. In the case of B cell stimulation with another B cell stimulant, the thymus-independent type II mitogen, anti-IgD-dextran, TGF-beta led to a similar small increase in sIgA expression, but caused suppression of IgA secretion. Using the Th2 cell clones CDC35 and D10 to stimulate resting B cells in a cognate and non-cognate T cell-dependent fashion, respectively, TGF-beta again increased sIgA expression to a similar small extent. TGF-beta at low doses (0.1 ng/ml) did not increase IgA secretion significantly and, at higher doses (1.0 ng/ml) caused significant suppression of IgA secretion. Addition of various cytokines (IL-2, -4, -5, D10sup) other than TGF-beta to stimulated B cells did not increase sIgA expression, but did give rise to increased amounts of IgA secretion, especially when activated D10 T cells were used as the B cell stimulant. Finally, the addition of an antibody against TGF-beta to cultures containing TGF-beta on day 2 led to partial or complete reversal of the inhibitory effects of TGF-beta on IgA secretion. In conclusion, TGF-beta causes a consistent, but small increase in sIgA+ B cells, in cultures of B cells stimulated by a variety of T cell-dependent or independent stimuli. In contrast, TGF-beta either promotes or inhibits B cell survival and IgA secretion, depending on the method of B cell activation. These results are most consistent with the view that TGF-beta provides only a partial or incomplete IgA switch signal but that additional factors are involved in IgA isotype switching and differentiation. PMID- 1602132 TI - Local T cell responses induce widespread MHC expression. Evidence that IFN-gamma induces its own expression in remote sites. AB - Local inflammation induces increased expression of MHC and other genes in the affected tissue because of the paracrine effects of cytokines such as IFN-gamma. We previously reported that one such process--local allograft rejection--was accompanied by increased expression of MHC in a remote tissue, namely kidney. To explore how local inflammation affects gene expression in remote tissues, we studied MHC, beta 2-microglobulin, and IFN-gamma expression in mice undergoing either of two T cell-dependent localized inflammatory processes: rejection of an ascites tumor allograft, and skin sensitization by oxazalone. As assessed by binding of radiolabeled mAb and by immunohistology, each stimulus increased MHC expression in many remote tissues, including liver, heart, pancreas, and kidney. This was associated with increases in steady state mRNA for class I, class II, and beta 2-microglobulin. MHC induction was inhibited by the in vivo administration of cyclosporine or anti-IFN-gamma mAb and did not occur in nude mice, confirming the key role of IFN-gamma released from T cells. When we examined tissues of mice with these localized inflammatory lesions for IFN-gamma mRNA levels by polymerase chain reaction, we found that IFN-gamma steady state mRNA levels were increased in the spleen and, more surprisingly, in the kidney, and in uninvolved skin. Moreover, anti-IFN-gamma inhibited the induction of IFN gamma mRNA in the kidney, suggesting that IFN-gamma expression was induced by IFN gamma in an autoregulatory fashion. Thus the systemic MHC induction accompanying local T cell-mediated inflammation reflects the release of IFN-gamma from the site of inflammation, but may be amplified by the ability of IFN-gamma to induce its own expression in remote tissues. This self-amplification of IFN-gamma may contribute to the ability of local inflammation to induce extensive systemic effects. PMID- 1602133 TI - Immunomodulatory effects of transforming growth factor-beta on T lymphocytes. Induction of CD8 expression in the CTLL-2 cell line and in normal thymocytes. AB - We investigated the role of transforming growth factor-beta 1 (TGF-beta) in regulation of T cell growth and differentiation. Treatment of CTLL-2 cells with TGF-beta inhibited IL-2-dependent proliferation and caused morphologic changes as well as increased adherence. A major change of phenotype in TGF-beta-treated cells was the de novo expression of CD8 alpha chain in 35% of cells, which required the continuous presence of TGF-beta. Of the CD8 alpha+ cells, 20 to 30% co-expressed CD8 beta chain. Increased CD8 expression occurred even in the total absence of cell growth, was not a consequence of growth inhibition, and was not a result of selective growth or survival of CD8+ cells. New RNA synthesis was required for TGF beta-induced CD8 alpha surface expression, inasmuch as this was prevented by treatment with actinomycin D. Northern blot analysis demonstrated that cells treated with IL-2 + TGF-beta rapidly accumulated mRNA encoding both chains of the CD8 dimer, to a level fourfold greater than control by 6 to 12 h. In contrast, the IL-2-dependent increases in IL-2R alpha, IL-2R beta, and Granzyme B mRNA levels in these cultures were profoundly inhibited by TGF-beta. When unfractionated murine thymocytes were stimulated with phorbol dibutyrate plus ionomycin and cultured with IL-2 + TGF-beta, an increase in CD8 alpha mRNA was seen and greater numbers of CD8+ cells with higher levels of CD8 alpha and CD8 beta surface expression resulted, as compared to controls treated with IL-2 alone. Furthermore, similar treatment of CD4-CD8-(double negative) thymocytes with TGF-beta induced de novo CD8 alpha expression by a substantial number of cells, and the majority of these CD8+ cells lacked TCR/CD3. These data suggest that TGF-beta has both positive and negative regulatory effects on the expression of gene products important for T lymphocyte differentiation and function. PMID- 1602134 TI - Strain-dependent restricted VH and VL usage by anti-bacterial levan monoclonal antibodies. AB - The immune response to polysaccharides is highly regulated and has several distinguishing features, including restricted clonotype and isotype expression. The basis for this highly restricted response is not fully understood. To address these questions in a systematic manner, we have generated a panel of 102 mAb from CBA/CaHN (CBA/Ca) and BALB/cAnN (BALB/c) mice after one and two injections of bacterial levan (BL), a beta(2----6)-linked polyfructosan with beta(2----1) linked fructose branch points (inulin determinant, In). This panel of mAb was examined for isotype, fine specificity, VH and VL region gene family usage and relationships between these parameters. After one or two injections of BL in both strains, mAb were IgM and IgG3. Fine specificity and VH/VL gene family usage differed markedly, however, between the two strains. Only 4% (2/51) of CBA/Ca mAb recognized the In determinant, whereas 77% (40/51) of BALB/c mAb recognized this epitope. In both strains, VH usage was restricted and certain families were overrepresented. In CBA/Ca mice, the overall response to BL was dominated by VHJ558 (45%, 23/51), the largest VH family, but VH36-60 (27%, 14/51) and VHJ606 (25%, 13/51) were also highly utilized and overrepresented. In BALB/c mice, the overall response to BL was dominated by VHJ606 (79%, 39/49 designated), a relatively small VH family. More importantly, after a single immunization with BL one particular VH/VL pair (VHJ606/ kappa 11) was used by 88% (36/41) of BALB/c mAb and was associated with In reactivity. In summary, BALB/c and CBA/Ca responses to BL differ in fine specificity and VH/VL usage. PMID- 1602135 TI - Heterogeneity of anticardiolipin antibodies defined by the anticardiolipin cofactor. AB - Anticardiolipin antibodies (aCL) found in sera from patients with SLE react with cardiolipin (CL) in the presence of a 50-kDa serum cofactor. The cofactor, which was identified to be beta 2-glycoprotein I by sequencing the N-terminal amino acids, not only enhances CL binding by antibodies in SLE but also depresses it by antibodies associated with syphilis. Cofactor-dependent binding of aCL in SLE to solid phase CL was competitively inhibited by the simultaneous addition of fluid phase CL but was unaffected by either prior or simultaneous addition of a high excess of the cofactor. Binding of aCL in syphilis to solid phase CL was competitively inhibited by either addition of the cofactor or fluid phase CL. aCL in SLE reacted with CL, PS, and PA in the presence of cofactor. In contrast, biotinyl-cofactor bound directly to these anionic phospholipids (PL) and also to PG. These results show that the cofactor-CL complex bears an epitope that confers recognition specificity for aCL in SLE, in contrast with direct CL recognition by syphilitic aCL. The direct binding of the cofactor to PL suggests that the cofactor dependence of aCL binding to PL is due to recognition by aCL of a unique epitope generated upon the formation of the cofactor-CL complex. PMID- 1602136 TI - Adhesion of B lymphoid (MPC-11) cells to type I collagen is mediated by integral membrane proteoglycan, syndecan. AB - Differentiating B lymphocytes undergo changes in cell-cell and cell-matrix adhesion that control their movement through a series of distinct microenvironments. The integral membrane proteoglycan, syndecan, is a candidate for mediating B lymphocyte-matrix interactions because it is expressed on B lymphocytes only at times when they associate with matrix, and because syndecan is known to behave as a matrix receptor on simple epithelia. However, syndecan from B lymphocytes is significantly smaller in molecular mass than syndecan from simple epithelia (85 vs 160 kDa) suggesting that syndecan may have distinct functions on these two cell types. Our study was undertaken to determine if syndecan mediates adhesion of B lineage cells to extracellular matrix. The murine myeloma cell line MPC-11 was used because syndecan is the only major heparan sulfate proteoglycan detected on these cells and because they express a form of syndecan almost identical to that found on normal B lymphocytes. Cell binding assays demonstrate that syndecan binds MPC-11 cells to type I collagen. Binding is inhibited by heparin, by pretreatment of cells with heparitinase or by growth of cells before the assay in chlorate, an inhibitor of sulfation. Solid phase assays show that syndecan purified from MPC-11 cells binds to type I collagen but not type IV collagen, laminin, or fibronectin. The interaction of MPC-11-derived syndecan with type I collagen is of relatively high affinity (Kd app = 143 nM) as measured by affinity coelectrophoresis. However, the 160-kDa form of syndecan isolated from epithelial cells has a greater than fourfold higher affinity for type I collagen (Kd app = 31 nM) than does the MPC-11 syndecan, suggesting that different molecular forms of syndecan have distinct ligand binding properties. These results demonstrate that syndecan can mediate B lymphocyte interactions with matrix and suggest that changes in syndecan expression during B cell differentiation are a mechanism for controlling B cell localization within specific microenvironments. PMID- 1602137 TI - Identification and characterization of the effector region within human C5a responsible for stimulation of IL-6 synthesis. AB - Human C fragment C5a is known to be a proinflammatory mediator and more recently shown to be a potent modulator of both humoral and cell-mediated immunity. We recently reported that natural and recombinant C5a induces the synthesis of IL-6 specific mRNA and secreted protein from human monocytes. Our studies using analogue peptides that are homologous to the carboxyl-terminal sequence of human C5a, indicate that the "effector" site for inducing IL-6 synthesis resides within the C-terminal region (C5a (70-74)) of the C5a molecule. C5a peptides containing the exact sequence of the natural factor were found to retain full agonist activity but exhibited low potency (0.01-0.1% of intact C5a). It was also shown that amino acid substitutions in the C5a peptides by aromatic/hydrophobic residues, outside the immediate effector site, resulted in analogue peptides with a substantial increase in potency relative to the most active natural peptide (C5a (56-74)). Moreover, these peptides approach the potency of natural C5a for induction of IL-6. Taken together, these results suggest that the inflammatory and immunoregulatory activities associated with C5a may, in part, be due to the synthesis of IL-6. PMID- 1602138 TI - Apoptosis is induced in cells with cytolytic potential by L-leucyl-L-leucine methyl ester. AB - Previous studies have demonstrated that the selective toxicity of leucyl-leucine methyl ester (Leu-Leu-OMe) for cytotoxic lymphocytes and myeloid cells is dependent on intracellular conversion to membranolytic metabolites by the acyl transferase activity of the granule enzyme dipeptidyl peptidase I (DPPI) that is enriched in these cells. The mechanism of cell death remained unclear, however, and was the subject of the experiments reported here. When human U937, HL60, or THP-1 myeloid tumor cell lines or murine CTLL-2 cells were treated with Leu-Leu OMe, early release of both cytosolic 51Cr and soluble [3H]TdR labeled DNA fragments was observed, whereas antibody + C treatment of these cells caused only 51Cr release. Killing of U937 or THP-1 cells by incubation with the lysosomotropic amino acid methyl ester, Phe-OMe also induced only 51Cr release without evidence of DNA fragmentation. Preincubation with Zn2+, a known inhibitor of endonuclease activity prevented Leu-Leu-OMe-induced 51Cr or [3H]TdR release from these cell lines, but had no effect on antibody + C or Phe-OMe-induced 51Cr release. Zn2+ also prevented Leu-Leu-OMe-mediated killing of normal human CD16+ NK cells. Zn2+ had no inhibitory effect on Leu-Leu-OMe uptake or intracellular conversion to (Leu-Leu)n-OMe metabolites by these cell lines. Moreover, Zn2+ did not inhibit 51Cr release from nonnucleated E or nucleated U937 targets induced by extracellular production of DPPI-generated metabolites of Leu-Leu-OMe. Thus, killing of cytotoxic lymphocytes and myeloid cells by Leu-Leu-OMe appears to be dependent on generation of metabolites with membranolytic properties, but cell death induced by this process does not involve simple lysis of the plasma membrane. Rather, intracellular production of DPPI generated (Leu-Leu)n-OMe metabolites appears to trigger, an additional Zn(2+)-sensitive process that is associated with induction of apoptosis in cells with cytolytic potential. PMID- 1602139 TI - Effect of glucocorticoids on C3 gene expression by the A549 human pulmonary epithelial cell line. AB - The third component of C, C3, is the key opsonin of the C cascade and is produced locally within the lung by pulmonary epithelial cells, macrophages, and fibroblasts. Because glucocorticoids regulate the maturation and expression of several physiologically important genes in pulmonary epithelial cells, we examined the effects of glucocorticoids on C3 mRNA expression and C3 synthesis by the human pulmonary epithelial cell line, A549. Treatment with dexamethasone enhanced C3 production in a time- and dose-dependent fashion such that concentrations of dexamethasone greater than or equal to 0.001 microM significantly increased C3 production on day 3 of culture. Natural glucocorticoids, corticosterone, cortisol, and 11-deoxycortisol also increased C3 concentrations in A549 supernatants. Both cycloheximide and the glucocorticoid receptor antagonist, RU486, individually inhibited the effect of dexamethasone on C3 production. Northern analysis demonstrated that the steady state 5.2-kb C3 message increased in A549 cells within 10 h of treatment with dexamethasone. RU486 inhibited the effect of dexamethasone on C3 mRNA expression. The integrity of the C3 thiolester bond, as measured by [3H]iodoacetic acid titration and hemolytic assay, was not disrupted by dexamethasone. We conclude that glucocorticoids such as dexamethasone enhance the expression of C3 mRNA and increase the production of functionally active C3 by A549 cells by a mechanism that is mediated by the intracellular glucocorticoid receptor. PMID- 1602140 TI - Administration of anti-IL-4 monoclonal antibody 11B11 increases the resistance of mice to Listeria monocytogenes infection. AB - The role of endogenous IL-4 in resistance to Listeria monocytogenes infection was investigated by in vivo administration of an anti-IL-4 mAb (11B11). Mice treated with 0.01 to 0.4 mg of anti-IL-4 mAb before L. monocytogenes challenge demonstrated a significantly reduced peak bacterial burden in their livers and spleens and accelerated bacterial clearance from these organs. In addition, histopathologic damage to the liver was reduced. Maximal protection was achieved by i.p. injection of 0.1 mg of anti-IL-4 mAb 2 or 24 h before L. monocytogenes challenge; treatment with anti-IL-4 mAb after injection of L. monocytogenes had no effect on antilisterial resistance. Anti-IL-4 mAb-treated and control Listeria infected mice exhibited similar patterns of IFN-gamma, IL-2, and IL-4 mRNA, as determined by polymerase chain reaction amplification of RNA extracted from spleen cells. In both anti-IL-4 mAb-treated and control mice, IFN-gamma, IL-2, and IL-4 mRNA were produced within 4 h after challenge. Cytokine mRNA levels were similar for anti-IL-4 mAb-treated and control mice, except for the greater amount of IFN-gamma mRNA in the anti-IL-4 mAb-treated mice at 4 h after L. monocytogenes challenge. IFN-gamma and IL-2 mRNA levels were sustained for at least 5 days, whereas IL-4 mRNA was undetectable by 3 days after challenge. There were no significant differences in the amounts of IL-4 and IFN-gamma detected in culture supernatants of spleen cells from anti-IL-4 mAb-treated and control Listeria infected mice. These results suggest that endogenous IL-4, a cytokine thought to be produced principally by Th2 cells, has a deleterious effect on host defense against the facultative intracellular pathogen L. monocytogenes. Administration of an anti-IL-4 mAb increases antilisterial resistance without causing a detectable shift to a Th1 type of cytokine response. PMID- 1602141 TI - Tumor necrosis factor induces genes involved in inflammation, cellular and tissue repair, and metabolism in murine fibroblasts. AB - TNF-alpha is a primary mediator of the inflammatory response and has been ascribed a wide range of biologic activities including the cytolysis of some but not all transformed cell lines in vitro. Since most cells, normal and transformed, will also be lysed if they are concurrently treated with inhibitors of transcription or translation, the ability to resist TNF lysis depends on the de novo induction of specific gene products. To identify genes that might be involved in the ability to resist TNF-mediated cytolysis, cDNA libraries enriched for TNF-induced genes were constructed and screened. Twenty-one genes that are induced by TNF were isolated. Ten of the cDNA clones were identified by DNA sequence analysis and function in inflammatory responses, tissue or cellular repair, or cellular metabolism. Seven genes were not identified and are novel. The remaining four genes are encoded in the mitochondrial genome. Interestingly, not all the mitochondrial transcripts are induced. This may reflect a fine tuning of certain components of mitochondria that may be necessary for survival after TNF treatment. PMID- 1602142 TI - HLA-J, a second inactivated class I HLA gene related to HLA-G and HLA-A. Implications for the evolution of the HLA-A-related genes. AB - Ragoussis and co-workers (Genomics 4:301) previously described a class I HLA gene (now designated HLA-J) that maps to within 50 kb of HLA-A. The nucleotide sequences of three HLA-J alleles are reported here. Comparison of the nucleotide sequences of HLA-J alleles shows this gene is more related to HLA-G, A, and H than to HLA-B, C, E, and F. All four alleles of HLA-J are pseudogenes because of deleterious mutations that produce translation termination either in exon 2 or exon 4. Apart from these mutations, the predicted proteins have structures similar to those of HLA-A, B, and C molecules. There is, however, little polymorphism at HLA-J and none at functional positions of the Ag-recognition site. The polymorphism is less than found for HLA-H another HLA-A-related pseudogene. HLA-J appears, like HLA-H, to be an inactivated gene that result from duplication of an Ag-presenting locus related to HLA-A. Nucleotide sequence comparisons show that the HLA-A, H, J, and G genes form a well defined group of "HLA-A-related" loci. Evolutionary relationships as assessed by construction of trees suggest the four modern loci: HLA-A, G, H, and J were formed by successive duplications from a common ancestral gene. In this scheme one intermediate locus gave rise to HLA-A and H, the other to HLA-G and J. PMID- 1602143 TI - Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. AB - The IL-6R system comprises two functionally different chains: a ligand binding chain (IL-6R) and a non-ligand-binding but signal-transducing chain (gp130). gp130 associates with the IL-6-IL-6R complex, resulting in the formation of high affinity IL-6 binding sites, and transduces the signal. A cDNA for murine gp130 has been cloned from the cDNA library of murine macrophages by using a human gp130 cDNA as a probe. The overall homology with human gp130 was 76.8% at the protein level. The extracellular region of murine gp130, as observed in human gp130, comprises 6 U of a fibronectin type III module and part of this region of approximately 200 amino acids has typical features of a cytokine receptor family. Cloned murine gp130 could transduce the growth signal in a murine IL-3-dependent cell line in response to a complex of IL-6 and soluble IL-6R. Two species of murine gp130 mRNA (7 and 10 kb) were expressed in almost all the cell lines. These transcripts were also ubiquitously expressed in murine tissues, embryonic stem cells, and embryos as early as day 6 of gestation. Administration of IL-6 in mouse caused up-regulation of the gp130 mRNA levels in several tissues. Both gp130 and IL-6R mRNA in liver were up-regulated in vivo by IL-6. PMID- 1602144 TI - Enterotoxins in acute infective diarrhoea. PMID- 1602145 TI - Bacteraemic pneumococcal pneumonia: a continuously evolving disease. AB - During an 8 year prospective study of community-acquired pneumonia (CAP) requiring hospitalisation we found that 47 of 1118 (4.2%) patients had Streptococcus pneumoniae bacteraemia. Females outnumbered males 27:20. The mean age was 63.4 years and 25% of our patients were admitted from a nursing home. A comparison with the 1071 other patients with CAP showed that patients with bacteraemic pneumococcal pneumonia (BPP) were more likely to be female and to have alcoholism, diabetes mellitus, and chronic obstructive pulmonary disease as co-morbidities. The mortality rate of 19% in BPP was not significantly lower than the 22% rate for the remaining patients with CAP. Four of the nine (44%) patients with BPP who died, did so within 24 h of admission, compared with 29 of 236 (12.3%) (P less than 0.02) who died of CAP. A notable clinical feature was the absence of cough in 19% while overall in only 66% was the cough productive. Most of the patients had a non-specific clinical presentation. Fifty-three per cent had an uncomplicated stay in hospital. We conclude that bacteraemic pneumococcal pneumonia is a continuously evolving disease and for the first time may now be more common in women. PMID- 1602146 TI - Improved detection of infection by Escherichia coli O157 in patients with haemolytic uraemic syndrome by means of IgA antibodies to lipopolysaccharide. AB - Samples of serum from 125 patients with haemolytic uraemic syndrome, were screened for antibodies of the IgA and IgM classes to the lipopolysaccharide (LPS) of Escherichia coli O157:H7. By means of the techniques of ELISA and immunoblotting, 48 samples were shown to contain antibodies of the IgM class to E. coli O157 LPS, while 42 samples contained IgA antibodies to this O-antigen. Thirteen patients produced IgM but not IgA antibodies to the LPS of E. coli O157:H7. Of 42 patients with IgA antibodies to the E. coli O157 LPS, seven did not produce antibodies of the IgM class. From this study, screening patients' serum for antibodies to E. coli O157 LPS of the IgA class, in addition to those of the IgM class, a total of 55 patients were shown to be seropositive. This constituted an increase is in the sensitivity of obtaining evidence of infection by this organism by 12%. PMID- 1602147 TI - Adherence of Helicobacter pylori to HEp-2 cells. AB - The adherence of 25 strains of Helicobacter pylori was evaluated in HEp-2 cells. These bacterial isolates, obtained from Chilean patients with gastric disorders, were also tested for haemagglutination of human red blood cells. Adherence of HEp 2 cells was expressed as a common property of all strains, irrespective of whether the cultures were grown on semi-solid or in liquid media. Previous reports that haemagglutinating activity was present in cells grown only on semi solid media were confirmed. Adherence to HEp-2 cells was suppressed when bacterial cells were pretreated with homologous or heterologous whole human serum, containing specific antibodies of H. pylori. Adherence remained unaltered when bacterial cells were similarly treated with normal serum lacking specific antibodies. These observations imply that adhesions are expressed in vivo and suggest that an adherence mechanism, not depending on the expression of specific haemagglutinin antigen, operates for H. pylori. PMID- 1602148 TI - Helicobacter pyrlori in Malawi, central Africa. AB - A total of 160 adult Malawians with epigastric pain for longer than 2 weeks was investigated by endoscopy and serologically for evidence of infection with Helicobacter pylori. The organism was demonstrated histologically and/or by culture in 141 (88%) patients. With histological means and/or culture as the 'gold standard', the histological technique was 100% sensitive while culture was only 81% sensitive. All isolates tested were sensitive to amoxycillin and tetracycline; 74% were resistant to metronidazole. Endoscopic findings were normal in 104 (65%) patients (86.5% H. pylori positive). Evidence of duodenal ulcer was found in 41 (25%) patients (95% H. pylori positive). Histologically, gastritis was common, severe gastritis being associated with increased colonisation by H. pylori. Two kinds of urease test were found to be 100% specific for the presence of H. pylori. The sensitivity of the serological test (Helico-G test) was 98% but its specificity was only 27%. These results provide important background information for planned therapeutic studies in patients with upper gastro-intestinal disease in Malawi. PMID- 1602149 TI - Feto-maternal listeriosis in Denmark 1981-1988. AB - We collected clinical information about 30 cases of Listeria monocytogenes infections in pregnancy, which occurred in Denmark between 1981 and 1988. The incidence of feto-maternal listeriosis was approximately one case per 100,000 live births in the early 1980s but increased to 25.3 cases per 100,000 live births in 1986. Listeriosis in Denmark occurred in two different patterns: endemic, in which the feto-maternal cases were a small proportion of the total, and epidemic: cases due to strains which were indistinguishable by phage-typing, and having a higher proportion of feto-maternal cases, as was seen in the outbreak of 1985-1987. The study group comprised 11 cases of intra-uterine death, three of maternal septicaemia without infection of the fetus and 16 cases of neonatal infection. Most neonates were ill at birth or became so within the first 24 h. The overall mortality rate among liveborn infants was 10.5% (2/19). PMID- 1602150 TI - Humoral antibody response in Leishmania tropica infection. AB - A small epidemic of Leishmania tropica infection was detected in Rajasthan, India. Most cases were in the 21-25 years age group and were possibly related to outdoor activity. Nearly one third of the patients had more than five lesions, the maximum number of lesions being confined to the face, neck and extremities. As determined by ELISA, 90% cases had leishmania antibodies with an OD range of 0.8-1.1. The serum of 60% of patients was positive by CIEP against L. tropica promastigote soluble antigen. By immunofluorescence, 96% persons were positive when L. tropica promastigotes were used as the substrate. The prevalence of infection with L. tropica appears to be much higher than that reported earlier. PMID- 1602151 TI - Treatment of Haemophilus aphrophilus endocarditis with ciprofloxacin. AB - A patient with Haemophilus aphrophilus endocarditis was successfully treated with ciprofloxacin. The response to treatment with cefotaxime and netilmicin for 12 days was poor but was satisfactory to a 6 weeks' course of ciprofloxacin. PMID- 1602152 TI - Fusobacterium nucleatum bacteraemia with multiple liver abscesses in an HIV-I antibody positive man with IgG2 deficiency. AB - Liver abscess formation due to Fusobacterium nucleatum is rare. We describe an HIV-I antibody positive man, with normal surrogate markers of cell-mediated immunity, who presented with F. nucleatum bacteraemia and liver abscess formation. He was found to have IgG2 subclass deficiency. This case illustrates the clinical importance of altered B-cell function in patients who are at an early stage of HIV disease. PMID- 1602153 TI - Treatment of ringworm: old remedy vs. new. PMID- 1602154 TI - Rapid diagnosis of tuberculous meningitis. PMID- 1602155 TI - Staphylococcus lugdunensis endocarditis. PMID- 1602156 TI - The rare sialadenoma papilliferum. Report of a case and review of the literature. AB - Sialadenoma papilliferum is a rare benign tumor of salivary gland origin. A case is described of a 46-year-old man with an exophytic lesion at the junction of the hard and soft palate. The literature is briefly discussed. PMID- 1602157 TI - New indirect method for estimating the birth prevalence of the Apert syndrome. AB - An indirect method for estimating the birth prevalence of the Apert syndrome is presented. The fraction of Apert syndrome patients in large clinical surveys of all cases of craniosynostosis is calculated and the fractional component obtained is multiplied by the known birth prevalence of craniosynostosis in general. Apert syndrome makes up approximately 4% of all cases of craniosynostosis. Using a weighted average estimate, birth prevalence was calculated to be 13.7/1,000,000. The results of the indirect method compare favorably with those obtained by the direct method. Nevertheless, because the indirect method is based on a number of assumptions that are easily violated, we cannot recommend its general use except under special conditions. PMID- 1602158 TI - Melkersson-Rosenthal syndrome. Review of literature and case report. AB - A case of Melkersson-Rosenthal syndrome with the classic triad of symptoms is presented. The literature is reviewed with respect to clinical presentation, differential diagnosis, pathogenesis, and management of this syndrome. PMID- 1602159 TI - Distraction osteogenesis of the mandible. An experimental study on sheep. AB - Distraction bone healing has been studied in long bones but there are only few experiments reported in relation to the mandible. The histological pattern of the healing process after mandibular distraction is described. After osteotomy the mandibles of 17 growing sheep were lengthened by gradual distraction using an external fixation device. The follow-up varied from 0 to 52 weeks. The results indicate that bone healing in mandibles is principally the same as in long bones. Four phases can be observed during the repair process: 1) formation of collagen aligned in the direction of distraction, 2) bone formation over the collagen template, 3) bone union across the distraction gap, and 4) remodelling of the lengthened segment. Some increased osteoblast activity was also seen in the control side. PMID- 1602160 TI - Efficacy of oral midazolam prior to intravenous sedation for the removal of third molars. PMID- 1602161 TI - Rigid internal fixation of mandibular fractures. An analysis of 270 fractures treated using the AO/ASIF method. AB - The results are reported on 214 patients treated for 270 mandibular fractures, using rigid internal fixation. Of these, 172 fractures (63.7%) in 131 patients had been re-evaluated at final follow-up in connection with plate and screw removal, on average 15.2 months, postoperatively. Although one-third of the patients had a history of alcohol abuse, and 86% were treated with a delay of more than 24 h (mean 3.2 days), good primary bone healing was observed in 93.9% of the patients. Infections, seen in 6.1% of the patients, were related exclusively to inadequate stability of the fracture. Malocclusion, observed in 18.2% of 159 dentate patients, was caused by incorrect plate bending and insufficient fracture reduction. Immediate postoperative dysfunction of the inferior alveolar nerve in 58.1% of the cases, and of the mandibular branch of the facial nerve in 12.7%, was followed by almost total recovery 1 year after operation. It is concluded that rigid internal fixation is a reliable method of treatment, especially indicated for patients with reduced healing capacity and poor co-operation. PMID- 1602162 TI - Long-term follow-up of subcondylar fractures in children by electronic computer assisted recording of condylar movements. AB - Twenty-eight patients have been followed up for an average of 15.1 years after uni- or bilateral subcondylar fractures sustained during their growth period. The conservative treatment, using orovestibular plates, has been evaluated with special reference to clinical, radiographic and functional parameters. TMJ function was tested using an electronic computer-assisted recording system. Condylar remodelling occurred in only about half of the individuals. Nevertheless, because of the good esthetic and functional results there seems to be no indication for operative reduction of the displaced condyle during the growth period. PMID- 1602164 TI - Endotracheal tube damage during orthognathic surgery. PMID- 1602163 TI - Incidence of facial fractures resulting in hospitalisation in New Zealand from 1979 to 1988. AB - The incidence and aetiology of facial fractures resulting in admission to public hospitals in New Zealand in 1987 were investigated retrospectively from data collected by the Health Statistical Services. Data were analysed by the age group, ethnic origin and gender of those affected. During 1987 the overall incidence of facial fractures was 47.9/100,000 of the population. The highest incidence was for Maori males at 152/100,000. A comparison with data for the period 1979 to 1988 showed a decrease for the population as a whole but an increase for those who declared themselves to be Maori. Assault was the most common cause of facial fractures resulting in hospitalisation for both males and females. Sport was the second most common cause of facial fractures with rugby football contributing two-thirds of these. These results indicate where future preventive measures should be targeted. PMID- 1602165 TI - Autogenous maxillary bone grafts in conjunction with placement of I.T.I. endosseous implants. A preliminary report. AB - Small bone defects due to atrophic, traumatic or periodontal bone loss can be grafted with autologous bone grafts taken from the maxillary tuberosity. This study presents a 1-3 years follow-up of 22 patients who were treated according to this technique. Thirty-two implants were placed 6 months after bone grafting. All implants were functioning well at the time of investigation. PMID- 1602166 TI - Stereographic assessment of mandibular canal in relation to the roots of impacted lower third molar using multiprojection narrow beam radiography. AB - The position of the mandibular canal in relation to the superimposed roots of 173 impacted lower 3rd molars was evaluated radiologically. A multiprojection narrow beam radiography (MNBR) technique recently developed for oral radiography was applied in this study. This method enables stereoscopic examination of the area of interest. The mandibular canal was located bucally to the roots of 105 (61%) teeth, lingually to the roots of 57 (33%) teeth, and between the roots of 6 (3%) teeth. The relationship of canal to roots of 5 (3%) teeth was not possible to determine. Disagreement between radiological assessment and clinical observation was found in 4 (5%) of 80 operated teeth. The canal was visible at operation in 23 (29%) cases, which was predicted at stereographic examination in 21 (91%) cases. The MNBR stereographic technique is a useful method with high sensitivity (0.83) for evaluating the bucco-lingual relationship of the mandibular canal to the roots of a 3rd molar. PMID- 1602167 TI - Intraoperative histological evaluation of tumor resection borders without prolonging surgery. AB - Frozen sections permit an intraoperative check for margin clearance during tumor surgery. However, much time is usually lost while waiting for the evaluation of the specimens, especially if they are many. In 24 patients with oral cancer, biopsies were taken from the regions of the intended resection borders before beginning with the lymphadenectomy. While histological evaluation was being performed by the pathologist, the surgical team proceeded to remove the regional lymphatic drainage. This procedure offers the advantage of being able to evaluate a large number of frozen sections without substantially prolonging the operation. PMID- 1602168 TI - Combined latissimus dorsi-serratus anterior/rib composite free flap in mandibular reconstruction. AB - The serratus anterior/rib composite flap can be used alone or in combination with a latissimus dorsi myocutaneous flap in mandibular reconstruction. The combined flap is particularly useful in reconstructing large anterior mandibular defects, and 4 cases are described which illustrate its use both as a pedicled flap and as a free tissue transfer. PMID- 1602169 TI - Hemangiopericytoma of the head and neck region. A clinical and morphological study of three cases. AB - Whereas the morphological picture allows classification of malignant hemangiopericytomas with great accuracy, classification of hemangiopericytomas exhibiting a histologically and cytologically benign picture can be difficult. Three hemangiopericytomas of the head could be studied in detail both clinically and morphologically. Inspite of light, scanning and transmission electron microscopic, immunohistochemical and electron microscopic studies no reliable histological criteria indicative of the biological pattern of so-called "benign" hemangiopericytoma could be found. Thus, it appears appropriate to consider all hemangiopericytomas as potentially malignant. PMID- 1602171 TI - Caring is a gift of the heart. PMID- 1602170 TI - Fever after traumatic brain injury. AB - Fever or pyrexia is a common clinical phenomenon. Among survivors of traumatic brain injury, it may appear immediately after injury, signal the presence of infection or reflect dysfunction of the thermoregulatory system. Management of pyrexia must be distinguished from measures that seek to identify and remove the putative cause of fever. Guidelines for decision making regarding the nursing management of patients with fever are presented. Given the potential benefit of fever, the ability of most patients to tolerate temperature elevations and the adverse effects, costs and discomforts associated with therapy, our habit of automatically reducing temperature should be examined. PMID- 1602172 TI - Development of an acute stroke unit. PMID- 1602173 TI - New thoughts on reflex sympathetic dystrophy syndrome. PMID- 1602174 TI - Cardioembolic stroke. AB - Approximately 15% of ischemic strokes are the result of an embolism from a cardiac source. Patients with nonvalvular atrial fibrillation, acute myocardial infarction, ventricular aneurysm, rheumatic heart disease, prosthetic heart valves and other less common cardiac disorders are at an increased risk for cardioembolic stroke. Clinicians must distinguish cardioembolic from atherosclerotic strokes to provide unique management for each patient. The nurse plays a dynamic role in diagnosis, education and treatment of patients at risk or who have had a stroke from a cardiac source. Knowledge of the pathophysiologic mechanisms and treatment options is essential for the nurse to adequately manage patient care. PMID- 1602175 TI - Understanding external ventricular drainage. AB - An understanding of the ventricular system and cerebrospinal fluid production is essential to providing appropriate care to the patient undergoing external ventricular drainage. A brief operative procedure introducing an external ventricular drain is a valuable treatment for increased intracranial pressure; however, its value must not obscure the associated risk of infection. Critical nursing care associated with successful patient outcomes includes both comprehensive neurological assessments and appropriate external ventricular drainage system maintenance. PMID- 1602176 TI - Prognosticators of outcome after major head injury in the elderly. AB - In 195 elderly head-injured patients, Glasgow Coma Scale (GCS) scores (admission and 72 hours) and intracranial pressure (ICP) 0-12 days after injury were compared to 6 month Glasgow Outcome Scores. All patients remaining comatose at least 72 hours after injury died within 6 months. The mortality rate among patients with ICP greater than 20 mm Hg was higher both at 72 hours and at 6 months after injury. The 6 month mortality rate was 75% overall and 90% among patients with elevated ICP. This increased mortality in elderly patients with initially elevated ICP indicates that nurses and other health professionals should consider ICP as well as level of consciousness when counseling patients and families regarding the likely outcome after major head injuries. PMID- 1602177 TI - Clinical referents for nursing diagnoses. AB - Validation of nursing diagnoses is an essential step in developing knowledge for nursing practice and should be a major goal of the discipline. Nursing diagnoses must have clinical referents, that is, defining characteristics which appear in patient populations exhibiting specific nursing diagnoses. Selecting nursing diagnoses for patient populations, developing a list of defining characteristics and operational definitions for a nursing diagnosis, selecting a standard to discriminate among subjects and constructing an instrument to document the occurrence of defining characteristics in selected patient populations are preliminary steps in identifying clinical referents. Methodological concerns addressed in establishing clinical referents for nursing diagnoses included controlling confounding factors, determining sample size, conducting a pilot study, determining interrater reliability, selecting appropriate statistical tests, and identifying critical defining characteristics for a nursing diagnosis. PMID- 1602178 TI - Effects of a nursing education intervention on parents' knowledge of hydrocephalus and shunts. AB - The purpose of this nursing intervention study, which used a pre- and posttest design, was to determine the effect of an education program on parents' knowledge of hydrocephalus and shunt dynamics in a sample of parents of children with hydrocephalus. Study participants were parents of hydrocephalic children treated with an initial shunt or a shunt revision. The convenience sample of 41 subjects was divided into two groups (A or B). Group A participants were parents whose child received an initial shunt. Group B participants were parents whose child was admitted for a shunt revision. The shunt education intervention had three components: a shunt handbook, a preoperative teaching session with the clinical nurse specialist and a subsequent reinforcement teaching session. The pre- and posttest were the same seven multiple choice questions on hydrocephalus and shunts. In both groups, the pretest was given before the shunt education intervention. The posttest was given 2-3 weeks after the patient's surgery. There was a statistically significant change in the scores from the pre- and posttests for Group A (p = 0.0092). The nursing education appeared to have a positive effect upon this group's knowledge of hydrocephalus and shunts. PMID- 1602179 TI - Modulation of T cell responses with MHC-derived peptides. AB - T cells are activated by an interaction of their TCRs with a complex made up of antigenic peptide bound to the interhelical groove of MHC molecules. The helices lining the antigen binding groove of MHC molecules are felt to contribute several contact residues for TCR binding. Peptides derived from the amino acid sequences of these helices may be capable of modulating immune responses and aiding in the dissection of immune recognition. These studies address the effects of a peptide derived from the sequence of amino acids 68-83 of the IAk beta 1 domain (IAk 68 83) predicted to represent a portion of an antigen-binding helix on the IAk molecule. The IAk 68-83 peptide is bound by a monoclonal anti-IAk antibody and inhibits its binding to IAk-bearing cells. The IAk 68-83 peptide inhibits antigen dependent activation of the IAk+con-albumin restricted T cell clone D10.G4, and this effect is more pronounced at lower doses of antigen-presenting cells. The free peptide has a small effect in limiting binding of anticlonotypic antibodies to D10.G4, and a multivalent form bound to BSA has a more pronounced effect in this regard. The BSA-peptide conjugate, when fluoresceinated, specifically stained D10.G4 cells, and this was specifically competed by unfluoresceinated IAk 68-83 peptide-BSA conjugate, as well as by anticlonotype. These results suggest that peptides derived from the predicted helical region of MHC class II molecules may have a direct interaction with T cell receptors. Such peptides may be capable of modulating immune responses in a physiologically significant manner. PMID- 1602181 TI - Functional capacity of a tumor-infiltrating B-cell line: lymphokine secretion. PMID- 1602180 TI - Graft versus leukemia. PMID- 1602182 TI - Immunotherapy through the IL-2 receptor. PMID- 1602183 TI - Autoantibodies to brain and polynucleotides in patients with schizophrenia: a puzzle. PMID- 1602184 TI - In vivo cocaine administration influences lymphokine production and humoral immune response. AB - The effect of in vivo cocaine administration on in vitro mitogen-induced lymphokine production was examined. Splenocyte cultures from BALB/c mice treated with an acute (1 mg/kg) or daily cocaine administration (1 mg/kg/day for 7 consecutive days) were less responsive to induction of IFN-gamma, IL-2 and IL-4 production by mitogen stimuli. We also evaluated the humoral immune response to both a T-dependent (HEL) and a T-independent antigen (rHBcAg). It was found that cocaine inhibits T-dependent antibody production only. This inhibition was greatest when cocaine was given during immunization. The results suggest that T cell-mediated responses may be more affected by cocaine use/abuse. PMID- 1602185 TI - Assessment of the diagnostic value of the native PGLTB1, its synthetic neoglycoconjugate PGLTB0 and the sulfolipid IV antigens for the serodiagnosis of tuberculosis. AB - A major phenolic glycolipid (PGLTB1) from Mycobacterium tuberculosis, that resembles the phenolic glycolipid-I (PGL-I) from M. leprae, and its synthetic terminal diglycosyl conjugate (PGLTB0) were reported and raised the prospects of a specific serodiagnostic test for tuberculosis (TB). The diagnostic use of a sulfolipid, namely the SLIV, was also reported. The objective of this investigation was to assess the relative sensitivity, specificity, and predictive values of three ELISAs using the PGLTB1, the PGLTB0, and the SLIV as antigens for the serodiagnosis of TB. Similarly to leprosy patients for the PGL-I antigen, the TB patients responded preferentially in IgM against the phenolic glycolipid. We screened the sera from 191 active tuberculous patients, 29 healthy subjects living in France, 102 healthy Polynesian blood donors, 82 contacts of new TB patients, and 20 leprosy patients before treatment for IgG anti-SLIV, and for IgM anti-PGLTB1 and IgM anti-PGLTB0. TB patients showed significantly higher activity than did healthy Polynesians when tested against SLIV and PGLTB0, and the smear positive group gave higher activity than did the smear-negative but culture positive group, especially for IgG anti-SLIV. The leprosy patients did not show higher activity than the Polynesian controls. Respectively, for SLIV, PGLTB1 and PGLTB0 antigens, the specificities were of 95%, 85%, and 89%; the sensitivities of 36%, 16% and 15%; the efficiencies of 58%, 40% and 39%; the predictive values for a positive result, assuming a prevalence of 15% among patients with respiratory symptoms, were of 30%, 16% and 19%. PMID- 1602186 TI - Subgroups among lepromatous leprosy--a viewpoint. PMID- 1602187 TI - Immunology of a burnt-out lepromatous leprosy patient. PMID- 1602188 TI - Water-soluble complexes of palmitic acid and palmitates for metabolic studies and cultivation trials of Mycobacterium leprae. PMID- 1602189 TI - Multidrug therapy in multibacillary leprosy; experience in an urban leprosy center. AB - The article records the experience of treating multibacillary (BB, BL and LL) leprosy with multidrug therapy (MDT) in an urban leprosy center. The problem of leprosy is to be properly assessed throughout the Indian subcontinent because most of the epidemiological data from the areas labeled low-endemic have to be updated. The regularity of therapy must be ensured and monitored constantly, but in spite of our efforts to do so some factors were beyond our control, such as providing a means of livelihood for the migrants from other places. In addition, the intake of drugs also has to be periodically checked from the history and discoloration of skin and, most importantly, confirmed by performing random spot tests for dapsone in the urine. The main problems discussed are the difficulty in demonstrating acid-fast bacilli in slit-skin smears from the macular form of borderline leprosy (also called dimorphous macular) and, secondly, whether the duration of multibacillary therapy was adequate since only approximately 50% of our patients achieved smear negativity after taking MDT for the stipulated period of 24 months. Experiences from other centers have suggested that the duration of MDT should be prolonged in multibacillary patients to achieve smear-negative status. Yet another group notes that smear negativity is gradually achieved during the period of surveillance following stoppage of MDT after 24 months. These questions await more information from good centers with controlled field studies. PMID- 1602190 TI - Use of synthetic peptides corresponding to sequences of Mycobacterium leprae proteins to study delayed-type hypersensitivity response in sensitized guinea pigs. AB - In this work we report the synthesis of 10 peptides (P1-P10) corresponding to one or several segments of the amino acid sequence of proteins from Mycobacterium leprae: 65 kDa, 28 kDa, 18 kDa, and 28 kDa superoxide dismutase, recently renamed antigens 2L, 9L, 12L, and 14L, respectively. They were assayed in the guinea pig model for the induction of a delayed-type hypersensitivity response in M. leprae and BCG-sensitized animals. To sensitize the animals two schemes were used: either a single dose of 5 x 10(9) irradiated or autoclaved whole bacilli, or four weekly intramuscular injections each containing 500 micrograms of soluble extract of M. leprae (MLSE) in incomplete Freund's adjuvant. Because the second scheme used far too much antigen, we decided to use the first scheme for the experiments we report here. DTH reactions of sensitized animals were induced after 30 days with intradermal injections of 5 micrograms of MLSE and with each of the 10 peptides at three different concentrations: 250 micrograms, 100 micrograms, and 0.05 micrograms. All M. leprae-sensitized guinea pigs gave indurations of 10 mm or more with MLSE, which indicates that the animals were sensitized. None of them gave DTH indurations with 250 micrograms or 100 micrograms, but some of them had positive DTH reactions with the 0.05 micrograms doses of the synthetic peptides. This is most likely due to the fact that we have used an outbred strain of guinea pigs. The peptides were also tested at 0.05 micrograms in animals sensitized with BCG. P7 and P10 seem to be nonspecific peptides; the remaining peptides only induced DTH in the M. leprae-sensitized guinea pigs. P3 (segments 65-85 of the 65 kDa protein) induced a positive DTH in 58% of the tested animals. In other experiments, guinea pigs were sensitized with a single injection (500 micrograms) of each of the synthetic peptides. All animals, except those sensitized with P4 and P8, had positive DTH responses when the homologous peptide was used. Those sensitized with P2, P4, P5, P7, and P8 were able to produce indurations when MLSE was used for the induction of the DTH reaction. PMID- 1602191 TI - Histopathological monitoring of an immunotherapeutic trial with Mycobacterium w. AB - Immunotherapeutic trials with Mycobacterium w (M. w.) on multibacillary patients are in progress at two large hospitals in New Delhi. A total of 380 patients so far have been inducted into the trial. The histopathological profile of the initial 87 patients (52 in the vaccine group, 35 in the control group) who have now completed 2 years of treatment are presented in this report. The vaccine group received multidrug therapy (MDT) and eight intradermal injections of M. w. every 3 months; the control group had MDT with starch injections as a placebo. Skin biopsies were taken at induction and thereafter at every 6 months. The results show a significantly higher proportion of biopsies with histopathological upgrading and/or clearance of dermal granuloma among the vaccinated cases. The number of patients becoming bacteriologically negative was higher in the vaccine group. There was no increase in the degree of neural inflammation in the biopsies showing upgrading. The lepromin site biopsy in patients who converted to positivity after vaccination showed epithelioid cell granulomas as did the biopsies from the nodules developing at the vaccination sites. The histopathological observations confirm the additional immunotherapeutic effect of M. w. used along with standard MDT therapy. PMID- 1602192 TI - Cellular immune responses to mycobacterial heat shock proteins in Nepali leprosy patients and controls. AB - Sixty-three leprosy patients, representing the entire leprosy spectrum from tuberculoid to lepromatous disease, and 17 healthy Nepali subjects were tested for their T-cell responses to the purified p65 and p70 protein antigens of Mycobacterium bovis BCG using a lymphocyte proliferative assay. There was strong correlation between the responses to BCG and M. leprae and the responses to the two antigens. Patients and controls lacking a response to either of the whole cell preparations failed to respond to the purified antigens, while BCG responders at the lepromatous pole of the disease did mount a response to both antigens. Significant differences in the magnitude of the responses to these antigens were obtained between controls and the disease groups. In individual subjects, responses to the two antigens were significantly correlated to each other. PMID- 1602193 TI - T-cell responses of leprosy patients and healthy contacts toward separated protein antigens of Mycobacterium leprae. AB - Sonicated extracts of Mycobacterium leprae were separated by two-dimensional gel electrophoresis and electroeluted into 400 distinct soluble fractions. These fractions were probed with T lymphocytes from leprosy patients of different disease types, healthy contacts, and unexposed healthy individuals. Proliferative responses were visualized using three-dimensional stimulation profiles. T cells from many patients and contacts responded to a multitude of antigen fractions of different molecular masses and isoelectric points. T cells from unexposed individuals gave significant responses to lysates or whole organisms of M. leprae, but no or only marginal responses to separated antigen fractions. T cells of polar tuberculoid (TT) and the majority of polar lepromatous (LL) leprosy patients responded only to separated antigen fractions but not to lysates or whole organisms of M. leprae. The remaining LL patients were totally unresponsive and even failed to respond to separated M. leprae fractions. Thus, in some leprosy patients unresponsiveness to M. leprae seems to be caused by distinct components and can be broken by using separated antigen fractions; whereas in others, anergy remains. T cells of borderline tuberculoid (BT) patients, who were under chemotherapy, responded to separated antigen fractions as well as to lysates of M. leprae organisms. In contrast, BT patients who were untreated failed to react with any of the M. leprae preparations. Similarly, T cells of the majority of LL patients responding to separated fractions were under chemotherapy; whereas T cells from untreated LL patients gave no or only marginal responses to any of the M. leprae antigen preparations. These findings suggest some linkage between the degree of T-cell responsiveness and antileprosy drug treatment. PMID- 1602195 TI - Reflections on the elimination of leprosy. PMID- 1602194 TI - Effect of skin test with M. leprae soluble antigen on reaction to a subsequent test with the same antigen. AB - Soluble skin-test antigens (STA), produced from armadillo-derived Mycobacterium leprae by Drs. Rees and Convit, were expected to meet the long-felt need of a test for leprosy infection and also to serve as tests for measuring postvaccination sensitization induced by vaccine preparations against leprosy. The present paper reports results from two studies examining the influence, if any, of skin testing with Rees' STA on reaction to a subsequent test with the same antigen. In the first study, 2168 persons from households of leprosy patients and from neighboring households were skin tested with Rees' STA twice at an interval of 6 months. In the second study, 1700 persons, free from leprosy, received either Rees' STA or normal saline by random allocation. A random subset of 850 persons was tested with Rees' STA after 3 months. The remaining 850 persons were tested with Rees' STA after 6 months. In addition, 242 leprosy patients were given Rees' STA or normal saline by random allocation, and all of these patients were tested with Rees' STA after 6 months. The results of the two studies showed that among persons reacting with a small size of reaction to Rees' STA, the size of the reaction to the repeat test was significantly larger. However, from the results of the second study, which included a control group, it was clearly seen that the quantum of boosting or sensitizing effect of the first test as well as that of new sensitization was small over a period of 3-6 months.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602196 TI - Resolution of type 1 reaction in multibacillary Hansen's disease as a result of treatment with cyclosporine. AB - Type 1 Hansen's disease reaction (reversal reaction) is believed to result from a change in the immune response in patients with borderline Hansen's disease. The only effective therapy for significant type 1 reactions has been systemic corticosteroid therapy. Cyclosporine is an immunosuppressive drug which has been widely used in organ transplantation. We report a case of type 1 reaction complicating borderline lepromatous Hansen's disease. Cyclosporine therapy resulted in prompt and sustained resolution of the reaction. The possible mechanism of action of cyclosporine and the implications regarding the immunopathogenesis of type 1 reaction are discussed. PMID- 1602197 TI - How effective is monthly rifampin? PMID- 1602198 TI - Intralesional variation in histology. PMID- 1602199 TI - Evaluation of MLPA test for the serodiagnosis of leprosy. PMID- 1602200 TI - Does previous BCG vaccination interfere with the serodiagnosis of tuberculosis using Mycobacterium tuberculosis-specific glycolipid antigens? PMID- 1602201 TI - Subcorneal pustular dermatosis in type 2 lepra reaction. PMID- 1602202 TI - The leprosy game; a health education tool. PMID- 1602203 TI - Reactive oxygen intermediates in the phagocytes from leprosy patients: correlation with reactional states and variation during treatment. PMID- 1602204 TI - Can sandflies be the vector for leprosy? PMID- 1602205 TI - Comparison of PGL-I level with AFB numbers in foot pad suspension. PMID- 1602206 TI - Long-term follow up of lepromatous leprosy patients receiving intralesional recombinant gamma-interferon. PMID- 1602207 TI - Comparison of junctional diversity in the neonatal and adult immunoglobulin repertoires. AB - Junctional diversity in immunoglobulin (Ig) from an adult mouse contributes significantly to the size of the final Ig repertoire. In adult pre-B cells, N region addition and deletion of nucleotides form coding regions produces very heterogenous CDR3 sequences. In contrast, Ig from fetal and newborn mice show very restricted junctional diversity. The reasons for this are: (a) the lack of N regions; and (b) the predominance of certain junctional sequences. These common junctional sequences all appear to occur by targeted rearrangement to short stretches of sequence homology near the ends of the segments to be joined. Targeted rearrangement may play a role in the overexpression of certain Vh genes early in ontogeny. These non-random junctional sequences in the neonate will reproducibly create certain Ig, for example, the dominant T15 anti-PC antibodies. Thus the immune system first creates a small repertoire of predictable Ig sequences. To the extent that these Ig are expressed in long-lived B cells, these early Ig sequences may persist in the adult. Superimposed upon this early repertoire is an enormously diverse adult Ig repertoire. PMID- 1602208 TI - Organization and expression of the pseudo-light chain genes in human B-cell ontogeny. AB - In pre-B cells, the mu chain is expressed at the cell surface in association with a "light chain surrogate" encoded by the V pre-B and the lambda-like genes. This mu-psi-L complex presumably triggers early steps of the B cell differentiation, possibly by controlling the Ig gene rearrangements. In the humans, the lambda like complex contains 3 genes, located in the 22q11.2-q12.3 band, telomeric to the IGCL locus, with which they share a similar organization, pointing to a common genetic origin. Only one lambda-like gene, 14.1, is functional and specifically expressed with V pre-B in pre-B cells. This expression starts in cells which still have the IGH locus in germline configuration (pro-B stage) and ceases as soon as the IGL loci rearrange. These pre-B specific transcripts provide useful markers of cells of the B lineage in both physiological and pathological situations. PMID- 1602209 TI - The human VH repertoire: a restricted set of VH genes may be the target of immune regulation. AB - During the development of the immune system, a restricted set of VH gene segments provides the bulk of the immunoglobulin heavy chain repertoire. Most of these VH genes have been found later in life encoding autospecificities either in normals or in patients with autoimmune diseases. Additionally, there is considerable evidence that the fetal/neonatal B-cell repertoire is autoreactive and idiotypically connected. In the course of sequencing the heavy chain of a panel of human autoantibodies mainly derived from patients with autoimmune diseases, we found that one of the VH families, and more specifically one single VH gene contributes to a large extent to the adult autoimmune repertoire in restricted as well as unrestricted responses. This VH gene segment is not particularly overexpressed in the fetus. Since the only common element to these autoreactive responses is the region encoded by the VH gene itself, these observations may provide an important insight into B-cell regulation. PMID- 1602210 TI - Interrelating B cell subpopulations and environmental regulation with the expression of three tiers of repertoire diversity. AB - The B cell repertoire consists of three tiers of clonotype diversity. One tier, which is the product of H chain V region rearrangements in the absence of N additions, is of limited diversity (less than 10(8) clonotypes) so that clonotypes of this tier would be expected to recur within and among B cells of individuals of an inbred strain. These clonotypes, therefore, could be subjected to, and conserved by, evolutionary selective pressures such as those imposed by ubiquitous bacterial pathogens. The second tier of clonotypes is created by H chain V region rearrangements that include N additions, and is, therefore, exceedingly diverse. Clonotypes of this tier would be unlikely to recur; however, by providing maximal diversity they would ensure protection against a wide spectrum of pathogens. The third tier of diversity is that which is generated by the superimposition of somatic mutations on clonotypes of the other two tiers. This tier of clonotypes is reflective of the refinement of specificities that are destined for expression in memory B cells. B cells exists as three distinct subpopulations, Ly-1 B cells, conventional primary B cells and memory B cells. These subpopulations differ functionally, developmentally, and by the extent to which they are impacted by immunoregulatory processes. Furthermore, B cells of these subpopulations differentially express the three tiers of clonotype diversity. PMID- 1602211 TI - Expression and selection of murine antibody repertoires. PMID- 1602212 TI - Developmental origins, specificities and immunoglobulin gene biases of murine Ly 1 B cells. AB - Ly-1 B cells in mouse show numerous phenotypic and functional features that distinguish them from the bulk of IgDhigh/Ly-1- B cells. Their association with autoantibody production and the presence of Ly-1 on a group of murine B lymphomas that also exhibit certain specificities enriched in the normal population has stimulated continuing interest in this population. We have taken two approaches in our investigations of these cells: 1) defining the origins of Ly-1 B cells (the "lineage question"); and 2) studying the expression of particular specificities and associated immunoglobulin V genes enriched in this population. In this review we present the experimental background that supports our current understanding of Ly-1 B cells as the remnant of a fetal B cell differentiation pathway and suggest that the selection of cells from this fetal/neonatal population into the adult long-lived pool results in the over-expression of certain germline-encoded autoreactivities, such as antibody to bromelain-treated mouse red blood cells and intact thymocytes. PMID- 1602213 TI - Ontogeny of the immune system and the invisible frontier to immune regulation. AB - The data presented focus on three topics: 1) Self-reactivity of early B cells as a constitutive feature of the immune system; 2) Self-reactive V regions and their possible involvement in immune regulation; and 3) Autoantibodies directed at T cell surface molecules as a new form of direct regulation of the B cell repertoire on the T cell compartment. Evidence is provided for lack of substantial difference in the reactivity of neonatal hybridomas from normal and autoimmune mice, and the proposal is made that the immune systems of normal and autoimmune neonatal mice start with similar characteristics implying that avoidance of autoimmune disease is matter of active regulation through a process learned in ontogeny. Two general possibilities for immune regulation are discussed. One is based on the V regions of self-reactive antibodies and their antigenic determinants. The other is through natural autoantibodies able to interfere with the state of activation of T cells. It is concluded that the role of highly conserved structures like self antigens is to maintain immunoglobulin genes and favor their expression in the incipient immune system so that simple patterns of regulation can be set in motion and made available. PMID- 1602214 TI - Cytokines and Ly-1 (B1) B cells. AB - In an attempt to elucidate the possible role of cytokines in autocrine growth of Ly-1+B cells, and the role of this subset of B cells in immune regulation, both in normal and diseased hosts, we have performed a systematic analysis of cytokine production by a series of mouse Ly-1+B lymphomas, as well as normal peritoneal Ly 1+ and conventional B cells. The lymphomas all express TGF-beta, and some express IL-3 and IL-4. We observed that both the lymphomas and the peritoneal cells produce TNF-alpha, TNF-beta and IL-6. Another cytokine, IL-10, is produced predominantly by peritoneal Ly-1+B cells from healthy mice and by Ly-1+ B lymphomas, but not by conventional B cells. As IL-10 regulates the production of monokines and a subset of T-cell derived cytokines, our results suggest a broad immunoregulatory role for Ly-1 B cells. To complement these studies we have also examined the responses of Ly-1 B cells to mitogens and cytokines previously shown to stimulate conventional B cells. In summary, Ly-1 B cells, in contrast to conventional B cells do not respond to anti-Ig antibodies, even in the presence of IL-4. They do respond to LPS, and this response is preferentially enhanced by IL-5, and marginally enhanced by IL-3. Surprisingly LPS-induced proliferation of peritoneal B cells is inhibited by IL-6 and to a greater extent by IL-10. Whether this inhibition is a result of differentiation into Ig secreting cells is currently being evaluated. We discuss our findings in terms of the potential of Ly-1 B cells to regulate their own development and the immunocompetence of other cells. PMID- 1602215 TI - B cell subsets, idiotype selection: positive selection for some B lymphocytes? PMID- 1602216 TI - B cell ontogeny and repertoire expression. PMID- 1602217 TI - Expression of V gene families during ontogeny and establishment of B cell repertoire. PMID- 1602218 TI - Comparative expression of adult and fetal V gene repertoires. AB - A hallmark of the immune system is the extraordinary diversity associated with antibodies. This is made possible by a series of genetic rearrangements involving variable region gene segments. Considerable detail is known about these genetic mechanisms except for the enzymatic machinery involved. An important question in studies of the generation of diversity is whether V genes are selected for rearrangement mainly in a random manner or selected by particular developmental rules. Past studies have indicated that the acquisition of fetal and neonatal specificity repertoires is a nonrandom process. In this report, we review our studies that directly compare the adult and fetal/neonatal V gene repertoires. The evidence suggests that the adult repertoire is more diverse with indications of a random use of VH gene families. However, whether V genes are indeed randomly used in the adult remains to be clarified at the VH gene member level. The fetal repertoire, on the other hand, appears nonrandom in V gene usage. In addition, the fetal repertoire is mostly germline encoded with little evidence of junctional diversity. Taken together, the results indicate different rules for generation of the adult and fetal repertoires, findings most likely explain by distinct B cell subsets and B cell progenitors at early stages in ontogeny. PMID- 1602219 TI - Replies to Silver. PMID- 1602221 TI - From Israel: request for information. PMID- 1602220 TI - Replies to Silver. PMID- 1602222 TI - On cognitive process-based instruction: an introduction. PMID- 1602223 TI - Writing instruction from a sociocultural perspective: the holistic, dialogic, and social enterprise of writing. AB - This article considers the sociocultural perspective as a framework for writing instruction. Four assumptions of the perspective are examined and illustrated: Writing is a holistic cognitive activity; cognitive processes are learned in dialogic interactions with others; cognitive development occurs in students' zones of proximal development; and knowledge construction is a social and cultural phenomenon. PMID- 1602224 TI - Volleyball and other analogies: a response to Englert. AB - Englert and her colleagues have contributed much to our knowledge about effective writing instruction. They have demonstrated that interventions that make explicit the writing process and text structures are successful with students with learning disabilities as well as those without. Englert attributes this success to the holistic, social, and interactive nature of the instruction. However, one must keep in mind that CSIW was a package approach that included other validated instructional components. CSIW teachers presented conceptual models, used examples and nonexamples to illustrate text structure concepts, modeled thinking overtly while demonstrating the process, provided guided practice by prompting the process through dialogue and think-sheets, faded prompts as students took over more of the responsibility for the process, and taught for generalization by addressing more than one text structure and promoting student talk about the process. As Englert reported, most teachers seldom do these things, even when they claim to teach the writing process. Englert allows for the possibility that all students with learning disabilities may not be ready for cognitive strategy instruction as it is described in her article, and professionals must acknowledge that different techniques may be more effective for students of different ages and abilities. Swanson (1990) emphasized that there must be a match between strategy and learner characteristics and that strategies must be considered in relation to a student's knowledge and capacity. Strategic teaching requires that the teacher have a repertoire of approaches along a continuum that encompasses coaching students to use their own mental resources at one end and basic skill instruction at the other.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602225 TI - A developmental index using the Wechsler Intelligence Scale for Children: implications for the diagnosis and nature of ADHD. AB - The possible utility of Wechsler's Deterioration Index (WDI) in analyzing children's Wechsler Intelligence Scale for Children-Revised (WISC-R) results was explored in this study. Clinical records of children with learning disabilities (LD) and children with attention deficit-hyperactivity disorder (ADHD) were reviewed to determine if the WDI predicted the presence or severity of the disorders. The ages of the children ranged from 6 to 14. In two independent samples of children with LD (n = 35 and n = 26), the WDI did not predict LD status or severity. The LD samples were mostly male--85% and 57%, respectively. However, the WDI scores did significantly distinguish children with ADHD (n = 10) from nondisabled children (n = 10). The results were cross-validated on an independent sample of children with ADHD (n = 17) when compared to non-ADHD children (n = 22) who experienced significant behavioral difficulties. The ADHD samples were also mostly male--90% and 89%, respectively. The WDI classified only 59% of the children with ADHD and 86% of the non-ADHD children correctly. It is recommended that the WDI be considered a developmental index rather than a deterioration index in children. It is also recommended that significant WDI elevation (greater than .20) be considered to raise the question of ADHD, rather than simply yielding a diagnosis of ADHD. PMID- 1602226 TI - Computer-based reading and spelling practice for children with learning disabilities. AB - To examine the effects of computer-based reading and spelling practice on the development of reading and spelling skills, a pretest-training-posttest experiment was conducted in The Netherlands. Eleven girls and 17 boys with written language disorders (on the average, 9 years, 7 months old and performing 2 grades below age expectancy) practiced hard-to-read words under three conditions: reading from the computer screen, copying from the screen, and writing from memory after presentation on the screen. For all words, whole-word sound was available on call during practice. To assess learning effects, both a dictation and a read-aloud task were administered in which nonpracticed control words were also presented. During training, the computer kept record of several aspects of the pupils' learning behavior. It was found that copying words from the screen resulted in significantly fewer spelling errors on the posttest than writing words from memory, and that both forms of spelling practice led to fewer spelling errors than only reading words during practice. All three forms of practice improved to the same degree both the accuracy and fluency of reading the practiced words aloud. The way in which spelling and reading practice, in combination with speech feedback, support the development of phonological skills in children with written language disorders is highlighted in the discussion. PMID- 1602227 TI - Lexical and nonlexical routes: a comparison between normally achieving and poor readers. AB - This study investigated qualitative differences in poor readers relative to normally achieving readers of the same reading level. Thirty-eight 9-year-old poor readers and forty 7- and 8-year-old reading-age-matched normally achieving readers from the United Kingdom were matched in phonemic processing and then given tests of memory span and visual discrimination of letter-like characters, were required to read different word types (regular, exception, and pseudoword), and were asked to complete a homophonic pseudoword test. The poor readers were worse at reading pseudowords compared to the controls, but this difference was unrelated to phonemic length of number of letters, or to the ease of producing analogies for the pseudowords. The results suggest that although there are no differences with reading-age controls in phonological processing, poor readers have worse grapheme-phoneme conversion skills and greater reluctance to relinquish the lexical route when appropriate. The results also showed that poor readers were slightly better at visual discrimination but had poorer memory spans. PMID- 1602228 TI - An international perspective on learning disabilities: introduction to the special series. PMID- 1602229 TI - A Canadian perspective on learning disabilities. AB - Canadian practice and research with children and adults with learning disabilities are described and analyzed. After an examination of the historical basis for current practice, the societal and cultural factors affecting education of children with learning disabilities, services for adults, and research are discussed. It was found that policy and legislation regarding special education vary considerably from province to province, and identification practices and service delivery models vary even within provinces. The fact that Canada has two official languages (English and French), a large multicultural community, and a Native population with special needs often arising from poverty has an impact on the education of children with learning disabilities and on sample description in research. Although school-age children are relatively well served, services for preschool children and adults with learning disabilities are minimal. The positive features of Canadian service delivery are that most programs are publicly funded, decision making tends to be nonadversarial and collaborative, and the needs of the whole child are typically considered. PMID- 1602230 TI - A German perspective on learning disabilities. AB - German practices in the field of learning disabilities beyond preschool level are described in the context of their historical formation. In a historical perspective it becomes obvious that the German notion of Lernbehinderung, although being just a translation of "learning disabilities," differs markedly from the American definition. Definitional problems, educational practices, and emerging trends in the German field of "learning disabilities" are discussed. PMID- 1602231 TI - Learning disabilities in New Zealand: where kiwis and kids with LD can't fly. AB - Learning disabilities (LD) has never been officially recognized as a category of special education in New Zealand. This article discusses the main reasons for the rejection of the LD category. The education system in New Zealand is described, and the nature of special education is outlined to provide a context for considering LD. Attempts by the parent group SPELD (New Zealand Federation of Specific Learning Disabilities Associations) to have "specific learning disabilities" (SLD) recognized in legislation are discussed, along with reasons for the rejection of these attempts by state education officials. It is concluded that LD/SLD will never be recognized as such in New Zealand. The needs of students with LD may potentially be met by new policies for "high incidence" special needs. But teachers' lack of skills and strategies for working with a range of learning difficulties is seen as an impediment to students with LD being adequately helped in the foreseeable future. PMID- 1602232 TI - William Butler Yeats: dyslexic? PMID- 1602233 TI - A follow-along study of postsecondary outcomes for graduates and dropouts with mild disabilities in a rural setting. AB - Eighty-six students with mild disabilities living in a rural area who had graduated (n = 52) or dropped out of (n = 34) high school were interviewed at two points in time (7 months apart) about their employment, residential status, and participation in postsecondary education and training programs. Information was also collected on students' high school experiences (educational, vocational, and work) and the reasons they dropped out of school. Of the students who had graduated (Caucasian = 26, black = 25, and other = 1), 31 were male and 21 were female. Of the students who had dropped out (Caucasian = 18, black = 15, and other = 1), 22 were male and 12 female. It was found that the majority of graduates and dropouts were employed full-time at both interviews, and held jobs that paid above minimum wage and provided employee benefits, as well. Nevertheless, by the time of the terminal interview, graduates had worked proportionally more time since high school than dropouts and had been employed in their current job more than twice as long. Neither group of former special education students was particularly active in pursuing postsecondary education or training programs. Finally, these former students had participated in a limited range of educational and vocational experiences during high school, both in terms of diploma tracks and vocational education programs. The implications of the findings for long-term employment and community adjustment are discussed. PMID- 1602234 TI - The MMPI-2 profile of adults with learning disabilities in university and rehabilitation settings. AB - The primary purpose of this study was to compare the personality profiles of adults with learning disabilities attending a large state university (8 females, 8 males) to those participating in training programs in a rehabilitation setting (8 females, 18 males), in an attempt to identify affective variables that should be considered in transitional and postsecondary program planning. A secondary purpose of the study was to compare the performance of two groups of adults with learning disabilities (i.e., university and rehabilitation) to a normative group of college students. The mean age for all subjects was between 20 and 23 years. Findings from the study indicated that the personality profiles of individuals with learning disabilities in either a rehabilitation setting or seeking a university degree are significantly different from those of the normative population of normally achieving college students. The rehabilitation group in this study demonstrated feelings of social isolation, poor self-concept, self doubt, and extreme restlessness. Somewhat different profiles were seen with the university group as they indicated feelings of fear, obsessive thoughts, lack of self-confidence, self-doubt, and extreme self-criticism. Both groups demonstrated profiles of individuals under extreme short- and long-term stress leading to anxiety. The study also reviewed the relevance and appropriateness of using the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) that will have direct application for the assessment and intervention of adults with learning disabilities either in a rehabilitation setting or seeking a university degree. PMID- 1602235 TI - The relationship between phonological codes on memory and spelling tasks for students with and without learning disabilities. AB - The purpose of the study was to determine the degree to which 31 (23 boys and 8 girls) 13-year-old children with learning disabilities from Grades 7, 8, and 9 were comparable to younger (9-year-old) reading- and spelling-matched controls in (a) phonological similarity effects, (b) phonetically based misspellings, and (c) relationships between memory and spelling performance. Children with reading disabilities and reading-recognition-matched controls, subgrouped by spelling ability, were compared on their memory for phonetically similar and dissimilar word lists and types of spelling errors. The results indicate that children with reading disabilities who are matched to younger children on both reading recognition and spelling ability exhibit normal phonological effects on memory and spelling measures. Within each reading group, low spellers produced more semiphonetic errors than high spellers, and high spellers produced more phonetic errors than low spellers. Significant correlations between memory and spelling error measures were more frequent for children with reading disabilities when compared to controls matched on reading and spelling ability. It was concluded that the phonological performance of reading/spelling-matched children with reading disabilities is characterized by an overreliance on phonological codes, whereas their counterparts' performance reflects independent and less generalizable use of phonological substrates across tasks. PMID- 1602236 TI - Recognition of Histoplasma capsulatum yeast-cell antigens by human lymphocytes and human T-cell clones. AB - We have prepared a detergent extract from the cell wall and cell membrane of Histoplasma capsulatum yeast cells that is recognized by T cells from mice immunized with viable organisms or with the extract. A 62-kd antigen from this extract has been isolated and has been shown to be antigenic and to confer protective immunity in mice. In this study, we examined the in vitro proliferative response by human lymphocytes and human T-cell clones to both the extract from the cell wall and cell membrane and the 62-kd antigen, termed HIS 62. Seven healthy individuals were identified whose peripheral blood mononuclear cells responded to the cell wall and cell membrane extract from H. capsulatum yeast cells. Mononuclear cells from all seven individuals recognized histoplasmin. T-cell clones were generated from peripheral blood mononuclear cells from a single person using the extract from cell wall and cell membrane as the antigenic preparation. Nineteen clones were propagated; all expressed the surface phenotype CD3+, CD4+, T-cell receptor alpha/beta +. The clones were antigen-specific. Of 17 clones studied, none responded to extracts from Blastomyces dermatitidis or Coccidioides immitis or to tetanus toxoid. Sixteen of 19 clones recognized HIS-62 in vitro. Additional analysis revealed that cells from each of the seven individuals who responded to the extract mounted a proliferative response to HIS-62. Thus, the extract from the cell wall and cell membrane and HIS-62 are targets of the human cell-mediated immune response to H. capsulatum. Moreover, HIS-62 appears to be an immunodominant antigen. PMID- 1602237 TI - A wave of elevated intracellular free calcium spreads through human neutrophils during phagocytosis of zymosan. AB - The cytosolic concentration of free calcium ([Ca2+]i) plays an important role in the control of many neutrophil functions. In this study, we characterize the early rapid subcellular changes in [Ca2+]i that occur in adherent neutrophils during phagocytosis of zymosan particles, using both dual- and single-excitation wavelength Fura-2 ratio imaging. We observed a wave of elevated cytosolic calcium that began shortly after zymosan contact and propagated from the region of neutrophil contact with the zymosan throughout the cell at a rate of approximately 17 microns/s at 31 degrees C. The wave was initiated by both opsonized and unopsonized zymosan and occurred independently of extracellular calcium. Multiple characteristics of the [Ca2+]i signal (including the absolute and regional [Ca2+]i and wave properties such as amplitude, frequency, duration, and topography) may be responsible for the differential regulation of cellular functions in the neutrophil. PMID- 1602238 TI - Ontogenetic development, differentiation, and phenotypic expression of macrophages in fetal rat lungs. AB - Development, differentiation, and distribution of macrophages in fetal rat lungs were investigated immunohistochemically using anti-rat macrophage monoclonal antibodies. In the lung buds, RM-1+ macrophages were first detected on fetal day 13, and some showed reactivity for TRPM-2. They populated in the peribronchial mesenchyme of the lung buds, proliferated in loco, and showed no peroxidase activity in any intracellular organelles. Their immunophenotypic and ultrastructural features were consistent with those of primitive/fetal macrophages. By fetal day 16, some of them expressed ED1, but ED1+ cells were a minor subpopulation throughout the fetal period. On fetal day 18, ED2+ macrophages developed; some also were positive for RM-1, but the others were negative. Both the RM-1+ and ED2+ macrophages were major macrophage subpopulations and expressed Ki-M2R and/or TRPM-3; ED2+ and/or Ki-M2R+ cells are regarded as pulmonary interstitial resident macrophages. In organ culture, a similar expression of differentiation antigens by macrophages was confirmed. None of these macrophages cytochemically showed any peroxidase activity in vivo or in vitro. In the fetal stage, both RM-1+ and ED2+ macrophage subpopulations showed proliferative potential, suggesting their ability to proliferate and survive in vivo. PMID- 1602239 TI - Platelet activating factor enhancement of lipopolysaccharide-induced tissue factor activity in monocytes: requirement of platelets and granulocytes. AB - Incubation of platelet activating factor (PAF) with heparinized blood caused no induction of tissue factor activity in monocytes. However, when PAF was added in addition to weak lipopolysaccharide (LPS), it amplified the LPS effect by 80%. By using separated fresh cell populations resuspended in plasma, PAF was shown to have no enhancing effect when added to mononuclear cells incubated with platelet rich plasma in the presence of LPS. In contrast, when granulocytes also were included, PAF caused an almost 3-fold increase in LPS-induced tissue factor activity. A PAF antagonist blocked this effect and also reduced LPS-induced tissue factor activity of monocytes in whole blood in a dose-dependent manner. In the recombined cell incubation system, the maximal inhibition by the antagonist was observed in the presence of granulocytes. These data provide evidence for an effect of PAF on granulocytes that probably generates a product that, together with platelets, enhances LPS-induced tissue factor activity in monocytes. PMID- 1602240 TI - Carcinoembryonic antigen binding proteins on elicited peritoneal macrophages. AB - Carcinoembryonic antigen (CEA), a member of the immunoglobulin supergene family, is recognized by a specific 80-kd receptor on Kupffer cells and alveolar macrophages. Peritoneal macrophages were harvested from male Sprague-Dawley rats 72 h after intraperitoneal injection with thioglycolate broth and from unstimulated animals. The elicited peritoneal macrophages had a much greater capacity to endocytosed CEA than the cells isolated from unstimulated animals. They took up CEA in a concentration- and time-dependent manner. Cellular uptake was temperature and colchicine sensitive indicating internalization of CEA. The process was saturable and could be specifically inhibited by CEA and nonspecific crossreacting antigen (NCA), a member of the CEA supergene family. Two binding proteins of approximately 35 and 80 kd were isolated from the surface of the peritoneal macrophages by affinity chromatography on a CEA-Sepharose column. Using CEA coupled to sulfo-succininidyl-2-[p-azidosalicyl amide]-1,3' dithiopropionate (SASD), a photoactivatable crosslinker, two binding proteins of 55 and 80 kd were identified on the surface of live peritoneal macrophages. The specificity of CEA endocytosis and binding proteins exhibited by the elicited peritoneal cells are similar to that previously reported for Kupffer cells and alveolar macrophages. PMID- 1602241 TI - Stimulation of human monocyte and polymorphonuclear cell iodination and interleukin-1 production by epigallocatechin gallate. AB - (-)Epigallocatechin gallate (EGCg) stimulated iodination of human peripheral blood monocytes, polymorphonuclear cells (PMN), and human promyelocytic leukemic HL-60 cells, dependent on time, dose, and temperature. However, EGCg did not affect iodination of nonadherent peripheral blood mononuclear cells, red blood cells, or 11 other cultured cell lines. Although various immunoregulators such as lipopolysaccharide (LPS), opsonized zymosan, 12-O-tetradecanoylphorbol-13-acetate (TPA) and tumor necrosis factor stimulated PMN iodination to varying degrees, their ability to stimulate monocyte iodination was much lower than that of EGCg. Washout experiments demonstrated that contact with EGCg for less than 60 min irreversibly stimulated PMN and monocyte iodination. EGCg also potently stimulated the production of interleukin-1-like factor by monocytes. The data suggest that EGCg is a strong in vitro stimulant of human phagocytes. PMID- 1602243 TI - [Classification of varices and venous insufficiency]. AB - The problem of the classification of varicose veins is as old as phlebology itself. A number of attempts have been made to define and assess this anatomical entity, which is progressively better investigated and better treated. Chronic venous insufficiency is a more recent pathophysiological concept, which covers both superficial venous lesions and deep lesions, regardless of their cause and their expression, especially trophic, unequivocal and dominant. A brief review of the principal classifications clearly demonstrates the difficulty of reaching a consensus. The precise definition of varicose veins and chronic venous insufficiency suggests the proposal of a simple clinical classification into five stages of chronic venous insufficiency. Beyond stage II of symptomatic varicose veins, treatment is required and complementary investigations, especially functional, are justified. PMID- 1602242 TI - Flow cytometric analysis of nitric oxide production in human neutrophils using dichlorofluorescein diacetate in the presence of a calmodulin inhibitor. AB - Dichlorofluorescein (DCFH) oxidation assay measures hydrogen peroxide (H2O2), which is a derivative of superoxide anion. We found that a calmodulin antagonist, W-13, which is known to inhibit superoxide anion generation enhanced the capacity of human neutrophils to oxidize DCFH. To investigate this discrepancy we studied the role of nitric oxide (NO) in DCFH oxidation. Pure NO was capable of oxidizing DCFH, and the product formed had spectral properties identical to oxidized DCFH produced by H2O2. The arginine analog, NG-monomethyl-L-arginine (NMMA), which inhibits NO production, in combination with W-13 completely inhibited the stimulus-induced increase in DCFH oxidation. We conclude that the oxidation of DCFH in human neutrophils can occur by either H2O2 or NO. PMID- 1602244 TI - [Significance of venous endoscopy in the exploration and the treatment of venous insufficiency of the legs]. AB - From a pathophysiological standpoint, the analysis of superficial valve lesions provides arguments in favour of the existence of early reflux and widens the role of valves beyond a simple antireflux system. All valves are not the same. Study of their topography in relation to collaterals and perforators enables definition of their role and of the origin of preferential hemodynamic circuits. Therapeutically, the first indications of venous endoscopy were in the visual control of deep venous thrombectomy, then in the preparation of saphenous bypasses in situ. It enables confirmation of the devalvulation of a segment of long saphenous and obstruction of afferent collaterals without an incision, by the endoscopic insertion of "micro-umbrellas". In addition, endoscopy can be used to identify incompetent deep valves suitable for valvuloplasty. In the superficial venous system, endoscopy offers a third dimension in the identification of varicosities in complex zones, such as the popliteal fossa. Furthermore, the development of a system for the endoscopic obliteration of superficial veins (ligatures, laser, umbrellas, chemical glue) could simplify the treatment of varicose veins. PMID- 1602245 TI - [Endoscopic study of reflux of the saphenous valve]. AB - Saphenous venous endoscopy, invasive and non-physiological, enables the in vivo and in situ observation of the valve system. A saphenous vein has a preferential flattening axis parallel to the outside of the skin with two walls, internal and external, and two borders. A valve is inserted on one vein wall, with the valve horns being on the borders. The free borders of a bivalve are parallel with the surface of the skin. The valve system has an antireflux function. There are three main causes of reflux in the saphenous veins: 1. Transitory functional incompetence affecting valves of normal appearance. This incompetence results from valve inertia, flattening of the valve against the sinus wall and loss of co adaptation. Do active factors producing closure of the valve cup exist against such transitory incompetence? 2. Incongruity between the vein wall and valves. The intercorneal or commissural space allows reflux on the border of the vein. This is the commonest cause of reflux in varicose disease of the vein wall. 3. Actual valve lesions. A distinction is drawn between lesions due to thinning, elongation, stretching, splitting or tearing and those due to thickening, retraction or adhesion. Endoscopy has enabled us to discover cases of varicose disease with predominantly valvular lesions in young individuales in whom early lesions of the valve cup cannot be explained by venous wall disease and has led us to complete the classification of varicose disorders. PMID- 1602246 TI - [Significance of photoplethysmography in the diagnosis of deep venous insufficiency]. AB - In chronic venous insufficiency, photoplethysmography, in addition to the clinical and Doppler examinations, offers important informations in the differential diagnosis between deep and superficial venous insufficiency. It is a simple, reproductible, non invasive test with data similar to venous pressure measurements. Photoplethysmography permits to set up quantitative criteria of venous insufficiency. It establishes the role of reflux in the dysfunction of the leg venous pump, and makes it possible to adjust for prescription of additional explorations, in particular popliteal or femoral dynamic phlebography. Furthermore, photoplethysmography offers a solid criterion to differentiate between various therapeutic surgeries: surgery of the superficial network, surgery of collateral veins, surgery to restore the deep venous network. Moreover, photoplethysmography is a useful tool to quantitatively appreciate the results of the venous insufficiency treatment. In conclusion, photoplethysmography appears as an additional examination necessary for functional exploration in chronic venous insufficiency. Its use in practical angiology is going to develop in view of its interesting results and its reasonable cost. PMID- 1602247 TI - [Modified Vigoni's operation for the treatment of sclerotic hypodermatitis]. AB - Despite the new mechanical technologies help, particularly mercury pressotherapy, some lipodermatosclerosis are not easily treated and their prognosis is bad owing to their evolutive liability to sheathe the lower limb. For 2 years, we have been proposing to our patients the little practised in France Vigoni operation: one piece hypodermis plaque resection removing perforating and collateral veins and the fascia. PMID- 1602248 TI - [Endovascular echography]. AB - The author reports data obtained by endoluminal pre and post-therapeutical ultrasound imaging of the wall architecture and lumen morphology of the arteries and varicose veins. In these studies, 20 and 25 MHz probes were used. These probes were covered with a 1 to 1.6 mm diameter flexible catheter and were introduced into the lumen of the vessels. Then, the probe was mechanically oriented in order to give, in cross-sectional section and real time, 360 degrees 2D images. The anatomical elements of the vessel wall and lumen, visualized with this technique, were described. The intima and adventitia appeared as echogenic structures while the media appeared as a non echogenic structure. The characteristics of endoluminal reactions such as atheromatous plaque, stenosis, thrombogenic and sclerogenic reactions were described. In conclusion, endovascular ultrasound imaging shows, accurate images of the morphology and dynamics of the arterial and venous vessel lumen and wall. This new technology can be used helpfully before, during and after vessel medical or surgical treatment. PMID- 1602249 TI - [Raynaud's phenomena with trophic disorders]. AB - Among patients with Raynaud's phenomenon, the occurrence of digital necrosis constitutes a specific circumstance for at least five reasons: 1. Raynaud's disease seems unlikely, 2. a basic mechanism involving an organic vascular impairment, as opposed to a vasospastic mechanism, is highly probable, 3. extensive evaluation is necessary until the underlying disease is discovered, 4. these patients are at risk of amputation, and 5. conservative treatment is not sufficient and other treatments including hemodilution, epidural stimulation and prostacyclin must be envisaged. Careful specialized digital nursing is also necessary. When possible, a causative treatment might be considered. For all the above reasons patients with Raynaud's phenomenon combined with tip necrosis should be referred to physicians specialized in Vascular Medicine. PMID- 1602250 TI - [Raynaud's phenomenon and blood viscosity]. AB - Raynaud's phenomenon is mainly linked with cold provoked vasomotor perturbations, but also with rheological alterations since blood viscosity is enhanced by lowering temperature. Several methods are available for studying distal vascularization: peri-ungual capillaroscopy, digital plethysmography and laser Doppler. Digital arteriography must be reserved to serious ischemia regarding the general anesthesia needed to avoid spasm. All these methods explore especially the vessel wall. Conservely, blood viscosity which has been developed for 25 years investigates the content of the vessel. Since 1965, numerous hemorheological studies pointed out the rheological disorders, especially those concerning plasma and blood viscosity. The most usual viscometry abnormalities revealed erythrocyte hyperaggregation, red cell hypodeformability, blood and plasmatic hyperviscosity. In a comparative study, 46 patients with Raynaud's phenomenon were studied: we performed peri-ungual capillaroscopy, plethysmography and viscosity measurements. The results demonstrated a link between capillaroscopy and thixotropy. Both investigations are never normal at the same time in connectivites and never abnormal at the same time in Raynaud's disease (primary Raynaud's phenomenon). In conclusion hemorheological studies showed nearly normal rheological parameters in Raynaud's disease, but abnormal rheological parameters in secondary Raynaud's phenomenon. PMID- 1602251 TI - [Post-thrombotic venous disease of the legs. Current data]. AB - The post-thrombotic syndrome (PTS) is the first cause of the severe chronic venous insufficiency (CVI) of which the total cost is very high. The lack of precise definitions, the long latency time between the deep vein thrombosis (DVT) and the trophic changes, the difficulties in treating the post-thrombotic ulcers, are partly responsible for the difficulties in analysing the problem of the PTS (epidemiology, pathophysiology, exploration) and consequently for the lack of interest in this disease. The recent data show that: 1) trophic venous changes are not all of PTS origin, 2) calf DVT are not to be neglected concerning the PTS risk, 3) the calf deep valvular destruction and the calf perforating veins reflux play the first part in the PTS evolution, 4) we should take into consideration the whole venous hemodynamic function of the lower limbs (macro and microcirculation) when analysing the long term clinical and hemodynamical consequences of a DVT. Today, the best treatment of a PTS is still its prevention not only by a better diagnosis and treatment of DVT but also by a long term ambulatory elastic stocking therapy with the aim of prolonging the disease-free interval. PMID- 1602252 TI - [Traveller's thromboembolic disease. The economy-class syndrome]. AB - Economy class syndrome refers to a thrombo-embolic disease occurring generally after a long air flight, but it may follow long car trips or even simply abnormally long or uncomfortable sitting position such as in war shelters. So the term traveller thrombo-embolic disease would preferably be used. On the basis of 12 personal cases and literature review, it appears that the disease often begins on disembarkation, that pulmonary embolus is frequently the only and first sign, that the victims tend to be over 40 years, and that more than 50% of the patients present a risk factor such as previous venous thrombosis, cardiac insufficiency, hemostasis abnormality ... Although exact frequency of the disease is unknown, our patients should be aware of respecting some preventive rules. Frequent feet flexion-extension motions and correct hydratation are recommended. Elastic contention must be proposed to patients with history of venous stasis. Finally patients with previous thromboembolism must be anticoagulated with preventive heparin dose. PMID- 1602253 TI - Upper extremity venous duplex imaging. AB - Over 500 upper extremities have been imaged with the Duplex Scanner at the John J. Cranley Vascular laboratory. Venous anatomy and imaging techniques are presented. Reference points and zones for localizing abnormal findings are demonstrated. Abnormal venous pathology including case presentations of acute radial, basilic, cephalic, and axillary vein thrombosis are presented. Complications of subclavian and internal jugular vein catheterization are demonstrated. Soft tissue pathology including edema, lymphadenopathy, hematomas, cysts, and abscesses are visualized and differentiated. Duplex use for evaluation of aneurysm, pseudo aneurysm and graft surveillance has been increasing in frequency. Examples are demonstrated. PMID- 1602254 TI - [Significance of the determination of D-dimers in venous thrombo-embolic disease]. AB - Plasma measurement of D-dimers (DD) with the Elisa technique is very useful in the diagnostic approach of venous thromboembolic diseases: a low level of plasma D-dimers (500 micrograms/l when using the Elisa from Stago) allows to exclude the diagnosis of deep venous thrombosis or pulmonary embolism with predictive values of 94% and 98%, respectively. Such a diagnostic potential is particularly useful in the group of patients with inconclusive perfusion-ventilation scintigraphy (low or indeterminate probability of pulmonary embolism) which represent more than 50% of the patients with suspected pulmonary embolism. Presence of pulmonary embolism is suggested by levels above 4.000 micrograms/l in the collective of outpatients who are urgently referred because of clinical suspicion of embolism. PMID- 1602255 TI - Rheology of the post-thrombotic syndrome. AB - Due to its non-Newtonian behaviour, blood rheology should matter most in those parts of the circulation where the shear stresses are low, i.e. on the venous side of the vascular tree. Yet we know little about haemorheology in the venous system or in venous diseases. According to previous results, there is a significant rheological deficit in the presence of a venous thrombosis or its risk factors. This trial was designed to determine the flow properties of blood in post-thrombotic (PTS) syndrome. Patients suffering from PTS are compared to controls in terms of ex vivo rheological measurements to quantify the rheological behaviour of blood: blood and plasma viscosity, haematocrit, red cell aggregation, red cell filterability, erythrocyte sedimentation rate (ESR), plasma fibrinogen. The comparison shows that plasma viscosity, red cell filterability, ESR and fibrinogen differ significantly between patients and controls indicating a lack of blood fluidity in PTS. It is suggested that the rheological deficit and the venous pathology contribute to a disturbed microcirculation in the affected limb. The combination of both abnormalities might be crucial in causing the typical symptoms of post-thrombotic syndrome. PMID- 1602256 TI - [Erythrocyte aggregation and clinical course stages of venous insufficiency of the legs]. AB - A double vicious circle at the venule and capillary level had already been pointed out by J. Dormandy and G. Nash as a pathophysiologic mechanism of rheological disorders associated with venous insufficiency of the lower limbs. Afterwards, such disorders were found by many authors when ex vivo analysis were performed on venous insufficient patients. However the time of their onset and their evolution in the course of the disease remain unknown. We studied red cell aggregation and plasma fibrinogen in 67 patients depending on the evolutive stage: 1st stage: isolated functional disorders, 2nd stage: trunk varicose vein linked to ostial incompetence, 3rd stage: trunk varicose vein linked to ostial incompetence with chronic trophic skin changes. The results showed that red cell aggregation and fibrinogen values are increased with the severity of the diseases. The rheological parameters increase when compared to controls from the first stage. Within the studied population, we avoided skewed results due to age and fibrinogen level by covariance analysis. Therefore recorded differences were practically linked with erythrocyte aggregability. Thus, red cell aggregation appears to be both an aggravating factor and a severity marker of the disease, proving the relevance of a rheological treatment in the lower limb insufficiency. PMID- 1602257 TI - Nontuberculous mycobacterial infection of the lung in a chest hospital in Thailand. AB - In a continuing study on the occurrence of nontuberculous mycobacterial lung disease by screening sputum cultures and from clinical judgement, from 1979 to 1987, a second series of 42 patients were suspected of having pulmonary infection caused by nontuberculous mycobacteria. As identified by the WHO Collaborating Center for Mycobacteria in Prague, Mycobacterium avium complex was isolated from the greatest number of patients (21 or 50%); M. scrofulaceum from seven; M. kansasii from six, and M. gorgonae from four. The remaining four patients yielded one strain each of M. fortuitum, M. asiaticum, M. szulgai, and one with suspected M. simiae. However, clinical significance was confirmed in only 30 patients, 20 of whom had M. avium complex; three had M. scrofulaceum; three had M. kansasii, and one each had M. gordonae, M. asiaticum, M. szulgai, and suspected M. simiae. Retrospective analysis revealed that 24 of the 30 patients had pre-existing disease, including 20 who had tuberculosis. Blood examinations of 10 patients recalled so far proved negative for HIV infection. Diseases caused by nontuberculous mycobacteria is still rare in Thailand. PMID- 1602258 TI - Patients with prosthetic cardiac valves followed in southern Thailand. AB - Prospective follow-up of 174 post-prosthetic cardiac valves have been done at Prince of Songkla University and Hat Yai Regional hospitals since 1985. The total follow-up time was 549 patient-years (pt-yr). Thirty per cent had been followed for 1 year or less. Eighty-two per cent of the patients had their mitral valves replaced either singly or as part of a multiple replacement. Thirty per cent of the time, the prothrombin time was below therapeutic range. Major events did not appear to be different from other reports: 2.7 embolic events per 100 pt-yr, 3.2 major bleeds and 3.2 deaths which may eventually be as high as 4.4 if a portion of the lost patients was assumed to have died. Events related to prosthetic valves and anticoagulation seemed to occur predominantly 1-2 years after surgery. PMID- 1602259 TI - Endomyocardial biopsy: its diagnostic usefulness. AB - In order to assess the diagnostic usefulness of EMB in patients with clinically suspected myocardial diseases, with and without heart failure or dysrhythmias, a prospective study was carried out in 84 consecutive patients. With EMB, the histological diagnosis was considered specific in 33 patients (39.3%), confirmative in 12 patients (14.3%) and negative in 39 patients (46.4%). It was found particularly useful in patients with unexplained heart failure and idiopathic dysrhythmias and in the differentiation between restrictive cardiomyopathy and constrictive pericarditis. The procedure can be safely performed with minimal morbidity and there was no mortality in the present study. PMID- 1602260 TI - Nosocomial pneumonias-a comparison among normal and compromised hosts in Thailand. AB - In order to compare the etiology, clinical manifestation, and prognosis of patients acquiring nosocomial pneumonia, we studied and compared twenty normal hosts who acquired nosocomial pneumonia from Jan 1, 1989 to Dec 31, 1989 (group 1) with fifty-four immunocompromised patients with nosocomial pneumonia who were admitted between 1984 and 1990 (group 2). Both groups were similar in some patterns such as: gram-negative bacilli were common (75%, 60%), the chest roentgenogram showed initial localized lesions (75%, 73%), there was a history of prolonged hospitalization (27, 33 days) and a high mortality rate (60%, 50%). The differing findings were that the first group acquired pneumonia more often during the first 7 days after admission; transbronchial aspiration was believed to be the route of entry and most of the patients had productive cough. Blood cultures rarely yielded the organisms (5%). The second group had pneumonia at a mean of 33 days after admission, hematogenous spread to the lungs was common and blood cultures yielded the etiologic organisms more often (40.7%). PMID- 1602261 TI - Conservative management of degenerative knee: an experience with 508 cases at Ramathibodi Hospital. AB - An analysis of the physical management of degenerative joint disease (1,016 knees) conducted at Ramathibodi Hospital, Bangkok, during the period 1985-1989 indicates that degenerative knee occurs mostly among those in the middle and older age groups (41-70 years, mostly among those 51-60 years of age). Physical therapy is suitable for treatment because of its ease, low cost and safety. Long term follow-up showed that only 7.66 per cent required surgery. PMID- 1602262 TI - Prevalence and risk factors of protein energy malnutrition (PEM) in preschool children of Klong-Toey Slum, Bangkok, Thailand. PMID- 1602263 TI - Gastric emptying pattern in Thai infants. AB - Gastric emptying of milk from the stomach of Thai infants shows a biphasic pattern. At 40 minutes the amount of stomach contents is more than at 20 minutes. At 100 minutes, only 16 per cent of the initial amount was recovered. The results of our study can be used as a standard reference for further study in infants with other diseases. PMID- 1602265 TI - Case report with review of Aeromonas infection. AB - A 31-year-old woman with A. sobria infection and septicemia was reported. The patient was a known case of ANLL,M4 with incomplete remission following successive courses of chemotherapy. There were abscesses in the subcutaneous tissue of right knee and the liver at necropsy. Leukemic cell infiltration in various organs as well as the aforementioned organs were observed. Reported cases of Aeromonas infection with or without diarrhea were also reviewed. According to our knowledge the present case is the first reported case with A. sobria infection with liver abscess in Thailand. PMID- 1602264 TI - Transthoracic and transesophageal echocardiographic diagnosis of cor triatriatum: operation without catheterization in an adult patient. AB - Cor triatriatum presenting in adulthood is extremely rare. An 18-year-old female patient presented with a clinical picture masquerading mitral valvular heart disease. Both transthoracic and transesophageal echocardiography demonstrated a membrane in the left atrium with no other cardiac anomaly. The patient was successfully operated on without the need for catheterization. PMID- 1602266 TI - Pelvic actinomycosis in pregnancy: a case report and review of the literature. AB - The first reported case in Thailand of pelvic actinomycosis during pregnancy is presented. It occurred in a 38-year-old Thai female with a history of IUD wearing for 2 years until the symptoms of intermittent lower abdominal pain. She had a history of postcoital bleeding at 16 weeks' pregnancy and bleeding per vagina during labor at 40 weeks' pregnancy. Speculum examination showed an irregular, friable, easily bleeding mass (3-4 cm in diameter). The specimens of the mass at the posterior fornix were obtained for culture and pathological examination. Right tubo-ovarian complex measured 10 x 4 x 4 centimeters in diameter, extending through the cul-de-sac to the vaginal canal at the posterior fornix, was identified during exploratory laparotomy. Low transverse cesarean section was performed. The pathological diagnosis was actinomycosis of right fallopian tube and ovary. The patient was treated with tetracycline. PMID- 1602267 TI - Dynamics in the fine structure of schedule-controlled behavior. AB - The variability in the behavioral equilibrium established by six basic schedules was characterized. The measures were the pause preceding the first response in each interreinforcement interval; the mean rate of responding in each interreinforcement interval; and the relative frequency of each interresponse time. The temporal windows ranged across the 780-session exposure, across a session, and across the interreinforcement interval. A display of individual interresponse times as a function of time in the interreinforcement interval indicated clear recurrent responding at somewhat less than 3 Hz in every bird, even after extended exposure to a schedule and regardless of the contingency. No strong sequential dependencies in the interresponse-time distributions were identified. A simulator, based on a simple recurrent pulser, was presented that produced output similar to the obtained data. An archival data base of the behavior chronically maintained by the simple schedules was also generated. PMID- 1602268 TI - Computational behavior dynamics: an alternative description of Nevin (1969). AB - A computational processing behavior-dynamic model was instantiated in the form of a computer program that "behaved" on the task developed by Nevin (1969). In this classic discrete-trials experiment, the relative frequency of choosing a response alternative matched the relative frequency of reinforcement for that alternative, the local structure of responding was opposite that predicted by momentary maximizing (i.e., the probability of a changeover decreased with run length), and absolute and relative response rates varied independently. The behavior-dynamic model developed here qualitatively reproduced these three results (but not in quantitative and specific detail) and also generated some interesting, as-yet untested predictions about performance in Nevin's task. The model was discussed as an example of a stochastic behavior-dynamic alternative to algebraic behavior theory. PMID- 1602269 TI - An integrative model for the study of behavioral momentum. AB - Behavioral momentum is the product of response rate and resistance to change. The data on relative resistance to change are summarized for pigeons responding on single-key two-component multiple schedules, in the initial links of two-key multiple chained schedules, and in equivalent components of two-key serial schedules. For single-key procedures, the ratio of resistance to change in two schedule components is shown to depend on the ratio of reinforcer rates obtained in the presence of the component stimuli. For two-key procedures, the ratio of resistance to change in equivalent components is shown to depend on the ratio of reinforcer rates correlated with key locations. A model based on stimulus reinforcer contingencies that combines the reinforcer rates in schedule components summed over key locations and reinforcer rates correlated with key locations summed over components, each expressed relative to the session average reinforcer rate, gives a good account of the data. An extension of the relative law of effect for multiple schedules fails to provide a complete account of resistance to change, but both approaches are needed for a comprehensive understanding of behavioral momentum. PMID- 1602270 TI - Comparison of variance and covariance patterns in parallel and serial theories of timing. AB - Parallel and serial timing processes are analyzed for their account of the dynamics of intertrial responding in the peak procedure. A strictly serial model, such as the behavioral theory of timing (Killeen & Fetterman, 1988), does not fit the dynamic correlation pattern in the location and duration of the middle high rate responding portion of peak trials. In contrast, the parallel scalar expectancy theory model, with a sample for memory and threshold, does fit this pattern. A modification of the serial model is presented that also accommodates the within-trial covariance pattern. The modification, which is formally equivalent to a model for human tapping (Wing & Kristofferson, 1973), entails the addition of concurrent processes operating in parallel with serial timing. PMID- 1602271 TI - Diminishing marginal value as delay discounting. AB - The fundamental law underlying economic demand and exchange is the tendency for value of marginal units to diminish with increasing amounts of a commodity. The present paper demonstrates that this law follows from three still-more-basic psychological assumptions: (a) limited consumption rate, (b) delay discounting, and (c) choice of highest valued alternative. Cases of diminishing marginal value apparently due to pure intensity of reward may plausibly be attributed to the above three factors. The further assumption that maximum consumption rate may vary within and across individuals implies that some substances may be unusually addictive and that some individual animals may be unusually susceptible to addiction. PMID- 1602273 TI - Integrating metabolic pathways in post-exercise recovery of white muscle. AB - Purine nucleotides (ATP, ADP, AMP, IMP), creatine, phosphocreatine, lactate, pyruvate and glycogen were measured in rainbow trout (Oncorhynchus mykiss) white muscle following exercise to exhaustion. Estimates of intracellular pH permitted calculation of free concentrations of nucleotides ([nucleotide]f) required for most models of control of energy metabolism. Creatine charge, [PCr]/([PCr]+[Cr]), fell from 0.49 +/- 0.05 (mean +/- S.E.M.) to 0.08 +/- 0.02 with exercise but recovered completely by the first sample (2 h). Although [ATP] declined to 24% of resting levels and recovered very slowly, RATP, [ATP]/([ATP]+[ADP]f+[AMP]f), and energy charge, EC, ([ATP]+0.5[ADP]f)/([ATP]+[ADP]f+[AMP]f), recovered as quickly as creatine charge. Changes in [IMP] mirrored those in [ATP], suggesting that AMP deaminase is responsible for maintaining RATP and EC. Recovery of carbon status was much slower than recovery of energy status. Lactate increased from 4 mumol g 1 at rest to 40 mumol g-1 at exhaustion and did not recover for more than 8 h. Glycogen depletion and resynthesis followed a similar time course. During the early stages of recovery, calculated [ADP]f declined by more than 10-fold relative to the resting values. The resulting high [ATP]/[ADP]f ratios may limit the rate at which white muscle mitochondria can produce ATP to fuel glycogenesis in situ. It is postulated that the high [ATP]/[ADP]f ratios are required to drive pyruvate kinase in the reverse direction for glyconeogenesis in recovery. PMID- 1602272 TI - Mechanics of the animate. AB - Behavior is treated as basic physics. Dimensions are identified and their transformations from physical specification to axes in behavioral space are suggested. Responses are treated as action patterns arrayed along a continuum of activation energy. Behavior is seen as movement along a trajectory through this behavior space. Incentives or reinforcers are attractors in behavior space, at the centers of basins of lowered potential. Trajectories impinging on such basins may be captured; repeated capture will warp the trajectory toward a geodesic, a process called conditioning. Conditioning is enhanced by contiguity, the proximity between the measured behavior and the incentive at the end of the trajectory, and by contingency, the depth of the trajectory below the average level of the potential energy landscape. Motivation is seen as the potential of an organism for motion under the forces impinging on it. Degree of motivation is characterized by the depth of the potential field, with low motivation corresponding to a flat field and a flat gradient of activation energy. Drives are the forces of incentives propagated through behavior space. Different laws for the attenuation of drive with behavioral distance are discussed, as is the dynamics of action. The basic postulate of behavior mechanics is incentive tracking in behavior space, the energy for which is provided by decreases in potential. The relation of temporal gradients to response differentiation and temporal discrimination is analyzed. Various two-body problems are sketched to illustrate the application of these ideas to association, choice, scalar timing, self-control, and freedom. PMID- 1602274 TI - The synchronization of ventilation and locomotion in horses (Equus caballus). AB - Cine film and synchronized records of respiratory flow were obtained from Thoroughbred racehorses cantering on a treadmill at speeds of 9 and 11 m s-1. Horses and some other galloping and hopping mammals link their breathing and locomotion, taking exactly one breath per stride. Three theoretical mechanisms by which the movements of locomotion might drive ventilation are considered. (i) Flexion of the lumbosacral joint and the resulting forward sweep of the pelvis pushes the viscera against the diaphragm. However, back flexion lags behind ventilation at 11 m s-1 and could not exclusively drive ventilation at this speed. (ii) Loading of the thorax by the impact of the forelimbs with the ground might force air out of the lungs. If the respiratory system were damped sufficiently to perform as this mechanism requires, the work of driving ventilation would make up approximately 15% of the total work of running. In comparison with other estimates of the work of ventilation this seems improbably high. (iii) The observed phase relationship between displacements of the viscera, caused by the accelerations of the body during running, and respiratory airflow is not consistent with a tuned visceral piston mechanism driving breathing. Thus, it would seem likely that back flexion is likely to contribute towards driving ventilation but loading of the thorax and the visceral piston mechanism do not. PMID- 1602275 TI - Conditional inhibition of screening-pigment aggregation by lidocaine in crayfish photoreceptors and frog retinal pigment epithelium. AB - Lidocaine, at concentrations equal to or lower than those that inhibit fast axoplasmic transport, was found to interfere with the dark-adapting migration of the screening pigments along crayfish photoreceptors and within the cells of the frog retinal pigment epithelium (RPE). The effects of the anesthetic on pigment movements were studied in isolated eyes incubated under light or dark conditions in media of different ionic compositions. Treatment of crayfish eyes with 25 mmol l-1 lidocaine in normal Van Harreveld's saline arrested pigment migration to the dark-adapted position or caused migration towards the light-adapted position in the dark. Similar results were obtained with frog eyecups exposed to 5 mmol l-1 lidocaine in Ringer's solution. In each case, the inhibition of dark adaptation was reversible and dependent on the levels of Na+ and Ca2+ in the incubation medium. A dark-adapted position of both pigments was compatible with lidocaine treatment provided that low-Na+, or high-Ca2+ or Co(2+)-containing solutions were used. These results indicate that light-adapted and dark-adapted pigment positions in both types of retinal cells can occur in the absence of local nervous input. Further, the data suggest a direct effect of lidocaine upon the photoreceptors or RPE cells. The inhibition of pigment aggregation is interpreted to be a consequence of an anesthetic-induced increase in the permeability of the plasma membrane, which in turn affects the intracellular ionic balance that controls pigment position. PMID- 1602276 TI - Fura-2 measurement of cytosolic free Ca2+ concentration in corpus allatum cells of larval Manduca sexta. AB - Cytosolic free Ca2+ has been implicated in the regulation of the larval corpus allatum (CA) of the tobacco hornworm Manduca sexta since agents presumed to cause changes in intracellular Ca2+ concentrations affect both basal and neuropeptide modulated synthesis/release of the juvenile hormones. To determine whether differences in cytosolic free [Ca2+] in CA cells were associated with different levels of gland activity, methods were developed for dissociating CA cells with the retention of biosynthetic activity and for uptake by the dissociated cells of the fluorescent Ca2+ indicator Fura-2. Digitized fluorescence microscopy of the Fura-2-loaded cells enabled measurement of intracellular Ca2+ levels in individual cells. Intracellular free Ca2+ levels were measured in CA cells from selected days during the fifth larval stadium and were found to be highest when the CA were biosynthetically active. Treatment of CA cells from day 6 with the Ca2+ ionophore ionomycin elevated the intracellular Ca2+ level, corroborating the involvement of elevated intracellular [Ca2+] in ionophore effects on juvenile hormone (JH) and JH acid synthesis. The results of the study are considered in relation to our knowledge of the role of Ca2+ in the function of endocrine gland cells. PMID- 1602277 TI - Blood flow distribution in submerged and surface-swimming ducks. AB - Observations that the response of the avian heart rate to submergence varies under different circumstances have led to speculation about variability of blood flow distribution during voluntary dives. We used a radiological imaging technique to examine the patterns of circulating blood flow in captive redhead ducks (Aythya americana) during rest, swimming, escape dives, forced dives and trapped escape dives and have shown that blood flow distribution in escape dives was the same as that in ducks swimming at the water surface. The response during trapped escape dives, however, was highly variable. Blood pressure was unchanged from the resting value during all activities. Predictions made about blood flow distribution during unrestrained dives on the basis of heart rate and other indirect data were confirmed in this study. However, the trapped escape dive responses indicated that heart rate alone is not always a reliable indicator of tissue blood flow in exercising ducks. PMID- 1602278 TI - Calcium transport by isolated skin of rainbow trout. AB - The skin overlying the cleithrum bone of freshwater-acclimated rainbow trout contains numerous mitochondria-rich (MR) cells, as detected by DASPEI fluorescence. This tissue was mounted in vitro in an Ussing-style chamber with fresh water on the mucosal surface and saline supplemented with bovine serum albumin on the serosal surface. The preparation developed a high transepithelial resistance and a small transepithelial potential (Vt), positive on the serosal side. Radioisotopic flux measurements indicated that the preparation actively transported Ca2+ from the mucosal to the serosal surface, as assessed by the Ussing flux ratio criterion. Ca2+ transport was positively correlated with MR cell density. Cortisol pretreatment in vivo reduced MR cell density and increased Vt but did not significantly alter Ca2+ fluxes. Ca2+ transport was unaffected by adrenergic agonists (10(-5) mol l-1 adrenaline, clonidine, isoprenaline) or cyclic AMP stimulants (10(-3) mol l-1 dibutyryl cyclic adenosine monophosphate, db-cAMP, plus 10(-4) mol l-1 isobutylmethylxanthine, IBMX) applied to the serosal surface. The Ca2+ ionophore ionomycin (1 x 10(-6)-3.2 x 10(-6) mol l-1 on the mucosal surface) increased both unidirectional Ca2+ fluxes and caused Ca2+ to accumulate within the epithelium. Lanthanum (10(-4) mol l-1) did not inhibit unidirectional Ca2+ fluxes, but apparently displaced Ca2+ from binding sites on the mucosal surface. Unlike Ca2+, movements of Na+ and Cl- across the epithelium were passive, as assessed by the flux ratio criterion, and neither adrenaline nor db-cAMP plus IBMX had any effect on Na+ or Cl- fluxes or electrical properties. These results indicate that ion transport across the skin mediated by MR cells ('chloride cells') contributes to Ca2+ but not to NaCl balance in freshwater trout. PMID- 1602279 TI - Dimensional analysis of the ventricle of an in situ perfused trout heart using echocardiography. AB - The linear dimensions of the ventricle of an in situ perfused trout heart were measured with an ultrasound scanner. Using a pyramidal model, linear dimensions taken from real-time, two-dimensional, echotomographic images of the ventricle were used to calculate ventricular end-diastolic and end-systolic volumes and, by the difference between them, stroke volumes for various filling and output pressures. Stroke volumes calculated from the ultrasound measurements were significantly correlated with actual stroke volumes determined from cardiac output and heart rate and had a regression line slope close to one. Increases in stroke volume with greater filling pressures resulted from increased ventricular end-diastolic volume with constant end-systolic volume; end-systolic volumes were negligible. Maintenance of stroke volume with increasing output pressure was by increases in both end-diastolic and end-systolic volumes. Decreases in stroke volume with very high output pressures may result from convergence of end systolic and end-diastolic volumes. PMID- 1602280 TI - Transbranchial ammonia gradients and acid-base responses to high external ammonia concentration in rainbow trout (Oncorhynchus mykiss) acclimated to different salinities. AB - Transbranchial ammonia gradients and blood acid-base status have been examined in rainbow trout acclimated to fresh water (FW), 33% sea water (33% SW) and sea water (SW) and exposed to 1.0 mmol l-1 total ammonia (TAmm) at pH 7.9 for 24 h. At all three salinities trout maintained large negative (inwardly directed) NH3 and NH4+ gradients throughout the exposure, presumably by active excretion of NH4+ to counteract the passive inward diffusion of ammonia. Analysis of blood non respiratory acid-base status (delta H+m) revealed an acid load in FW trout and a base load in SW trout following 24 h of exposure. This indicates that active NH4+/H+ exchange predominates in FW whereas NH4+/Na+ is the principal exchange utilised in SW under these experimental conditions. The plasma TAmm load incurred during ammonia exposure increased with salinity. Compared to FW trout, plasma TAmm values were 34 and 73% higher in the 33% SW and SW trout, respectively, after 24 h. This cannot be explained by differences in the prevailing transbranchial PNH3 gradient because ambient PNH3 was substantially lower at the higher salinities (due to higher pK' and solubility values). We interpret the difference between FW and SW trout as an increased permeability to NH4+ in fish acclimated to the higher-salinity environments. Transbranchial diffusion of NH4+ is, therefore, probably more important as a route for ammonia excretion in SW than in FW trout, especially considering the favourable transepithelial potentials normally found in SW teleosts. In addition, increased NH4+ permeability implies that the toxicity of ammonia will be greater in seawater than in freshwater teleosts and should not simply be measured as a function of the unionised ammonia concentration when considering seawater-adapted species. PMID- 1602281 TI - Multiple myeloma--a curable disease? PMID- 1602282 TI - New aspects of asthma. AB - It has now become apparent that asthma, even in its mildest clinical manifestation, is a chronic inflammatory condition of the airways. There have been important advances in understanding the special features of inflammation in asthmatic airways and the role of critical inflammatory cells such as mast cells (important in the acute inflammatory response) and eosinophils, macrophages and T lymphocytes (involved in the chronic inflammatory response). Many inflammatory mediators have been implicated in asthma, and the development of mediator antagonists suggests that sulphidopeptide leukotrienes may play an important role in bronchoconstrictor responses. Cytokines released from many different cells in the airways are likely to be important in orchestrating and perpetuating the chronic inflammatory response. Chronic inflammation has effects on airway vessels, mucus secretion, smooth muscle and nerves, with evidence to suggest that there are structural changes which may lead to persistent airway abnormalities. The therapeutic implication of these new discoveries is that much earlier use of anti-inflammatory treatments (such as inhaled steroids) is preferable to reliance on bronchodilators which do not control the underlying inflammatory process. PMID- 1602283 TI - The role of zinc in acquired immunodeficiency syndrome. PMID- 1602284 TI - Cognitive function, insulin-dependent diabetes and hypoglycaemia. AB - A series of seven psychometric tests, to evaluate mental concentration and the ability to retain selective attention, lexical fluency, wordlist memorizing and psychomotor speed, was performed on 25 non-diabetic control subjects and 55 insulin-dependent diabetes (IDD) patients of similar social background and professional status. When tested, none of the diabetics was hypoglycaemic and these patients were divided into two groups: Group I: 30 IDD patients unaware of hypoglycaemia, and experiencing frequent and severe episodes of hypoglycaemia. Group II: 25 IDD patients aware of hypoglycaemia. Groups I and II had experienced the disease for the same period of time (17 +/- 13 vs. 14 +/- 11 years, respectively) and they had similar HbA1c levels (7.14 +/- 1.25% vs. 8.6 +/- 1.88%, respectively) and degenerative complications. Compared with the scores of the controls, the Group I scores were lower in four tests: trail-making part A (psychomotor speed; P less than 0.001) and part B (retaining selective attention; P less than 0.01), lexical fluency (P less than 0.01) and Rey auditory-verbal learning test (wordlist learning; P less than 0.05). Group II scores were lower in two tests: trail-making part A (P less than 0.01) and part B (P less than 0.05). In word memorizing, the performance of Group I was inferior to that of Group II (P less than 0.05). In general, these psychometric tests showed that IDD scores were lower than those of the controls, with an average of 67% for Group II and 80% for Group I. Chronic hyperglycaemia and severe hypoglycaemia may have a deleterious effect on cognitive performance. In particular, several severe episodes of hypoglycaemia could be responsible for permanent memory impairment. PMID- 1602285 TI - Ischaemic heart disease incidence by social class and form of smoking: the Copenhagen Male Study--17 years' follow-up. AB - The Copenhagen Male Study is a prospective, cardiovascular cohort study initiated in 1970 and consisting of 5249 employed men aged 40-59 years. A total of 4710 men, who had reported their smoking habits and were free of ischaemic heart disease, had their mortality recorded over a 17-year period: 585 men suffered a first incident of ischaemic heart disease (IHD), and 248 cases were fatal. There was a strong social gradient in the risk of IHD (Kendall's Tau B = 0.12, P less than 0.001). Adjusting for age, blood pressure, physical activity, body mass index and alcohol consumption in a multiple logistic regression equation, men in the lowest social class had a relative risk (95% confidence interval) of IHD of 3.6 (2.5-5.3) compared to men in the highest social class. We determined whether differences in smoking habits could explain at least some of this large increase in risk. Adjustment for the above factors and also inclusion of the form of tobacco smoked, the amount of tobacco smoked and presence or absence of inhalation, had very little effect on the estimate: the relative risk was 3.5 (2.4-5.2). There was no social gradient in age at the start of smoking. According to smoking habits, comparing social class V with social class I, the relative risk was 7.7 (2.6-22.4) in cigarette smokers, 6.0 (1.1-32.1) in pipe smokers, 3.5 (1.7-7.1) in mixed smokers, 2.25 (0.4-12.9) in cheroot smokers, 3.8 (2.4-5.9) in all smokers, 1.95 (0.8-4.6) in ex-smokers, and 4.7 (1.01-22.2) in non-smokers. In the upper social classes, 50-75% of IHD events could be ascribed to smoking, and in the lowest classes only about 20%. We conclude that the substantial social inequalities in risk of ischaemic heart disease are not accounted for by differences in smoking habits. PMID- 1602286 TI - Serum hyaluronan and aminoterminal propeptide of type III procollagen in primary biliary cirrhosis: relation to clinical symptoms, liver histopathology and outcome. AB - Hyaluronan (HA) and aminoterminal propeptide of type III procollagen (PIIINP), two biochemical connective tissue markers, were determined in 76 patients with primary biliary cirrhosis (PBC). The HA and PIIINP concentrations were significantly increased compared with controls (P less than 0.001). Both HA and PIIINP levels correlated significantly with conventional liver-function tests. All patients with stage IV PBC showed increased concentrations of both these variables. However, HA was a better marker with regard to prediction of development of cirrhosis as well as prediction of symptoms. Furthermore, HA also showed a negative correlation with time of survival (P less than 0.05). The present data indicate that HA is a more sensitive marker of liver damage in PBC than PIIINP. PMID- 1602287 TI - Neurocirculatory asthenia revisited: elevated arterial pressure at presentation is a marker for subsequent hypertension. AB - Neurocirculatory asthenia (NCA) is a fairly common functional disorder often encountered among military recruits. Symptoms in NCA tend to appear in waves, and are believed to disappear completely with the passage of time. Elevated arterial pressure is known to occur as part of the various haemodynamic manifestations of NCA. However, the exact prevalence of hypertension, as well as its long-term prognosis, is still unknown. The present case-control study was designed to address these two issues. The target population consisted of 370 patients with NCA representing two separate cohorts: patients diagnosed in 1979, 10 years prior to this study, and patients diagnosed in 1983-84, 5 years prior to the study. An overall 20% prevalence rate of mild hypertension at diagnosis was calculated for the entire study population. In total, 100 patients representing equal numbers of hypertensive and matched normotensive subjects from each cohort were re evaluated. At follow-up, hypertension was present in 27% (1979 cohort) and 30% (1983-84 cohort) of patients originally considered to be hypertensive. Hypertension was either non-existent (1979 cohort) or limited to a single case (1983-84 cohort) among originally normotensive individuals. In parallel, resting heart rate was higher in the hypertensive subjects of the 1979 cohort both at presentation (85.5 +/- 3.2 vs. 73.7 +/- 2.4 beats min-1; P less than 0.005) and at follow-up (79.6 +/- 3.2 vs. 70.0 +/- 2.5 beats min-1; P less than 0.01). These results indicate that hypertension complicates the diagnosis of NCA in 20% of patients and that, contrary to common belief, it cannot be regarded as another transient manifestation of this condition. Thus hypertension in this context is, as in the younger members of the population in general, a major risk factor for lifelong hypertension, rather than an inconsequential phenomenon. PMID- 1602288 TI - Geographical variation and time trends in the attack rate of coronary heart disease in five Swedish cities. AB - Based upon community myocardial infarction (MI) records in five Swedish cities, geographical variation and time trends in the attack rate of fatal and non-fatal MI have been evaluated. During the study period 1975-1982, a total of 7699 events were registered among men and 1823 events among women. The mean annual mortality was highest in the north, and a declining gradient in mortality was observed from the northern to the southern part of the country. The out-of-hospital death rate was highest in the north, while no difference in in-hospital mortality was observed. However, the geographical variation in the morbidity of MI was less consistent. Changes over time generally followed the same pattern in all cities. The attack rate of fatal and non-fatal MI tended to decline among women and men aged 60-64 years. The pattern was less consistent among younger men. Among women aged 50-59 years the mortality remained unchanged, but the attack rate of non fatal MI increased in all cities. This increase was not explained by inclusion of less severe infarctions. A considerable proportion, about 85%, were recorded as primary events, emphasizing the possible role of primary prevention in obtaining a decrease in the incidence of the disease. The results of this study support previous findings of an important regional difference in the mortality of MI in Sweden. However, the magnitude of the regional variation in the incidence of coronary heart disease might be overestimated if only the mortality pattern is studied. PMID- 1602289 TI - Acute and chronic liver disease associated with Yersinia enterocolitica infection: a Norwegian 10-year follow-up study of 458 hospitalized patients. AB - During the period 1974-1983, Yersinia enterocolitica infection was diagnosed in 458 hospitalized patients by antibody response or isolation of the micro organism. A total of 54 (11.9%) patients had acute liver infection, with significantly elevated serum levels (greater than or equal to 2-fold) of bilirubin and/or enzyme levels. Serious liver disease with cellular necrosis was observed in biopsy specimens from two of 12 patients examined; six had unspecific changes. The patients were followed up for 4-14 years (until 1987). A total of 22 (4.9%) patients were readmitted with chronic liver disease; in one case non specific microscopic changes developed into granulomatous hepatitis over a period of 3 years. In both the acute and chronic stages of disease, liver involvement was associated with involvement of other organ systems, and some patients developed multi-organ disease. Chronic liver disease was associated with positive tests for antinuclear antibody and rheumatoid factor, and with a high mortality. PMID- 1602290 TI - Acute and chronic pancreatic disease associated with Yersinia enterocolitica infection: a Norwegian 10-year follow-up study of 458 hospitalized patients. AB - During the period 1974-1983, Yersinia enterocolitica infection was diagnosed in 458 hospitalized patients by antibody response or isolation of the micro organism. Eight (1.75%) patients showed signs of acute pancreatitis with elevated serum or urine levels of amylase; two patients had acute insulin-dependent diabetes. The patients were followed up for 4-14 years (until 1987). Four patients were readmitted with chronic pancreatitis, and one with acute pancreatitis. Diabetes developed in two males and nine females; in seven cases this was associated with chronic conditions of possible autoimmune aetiology. In 1987 a significantly higher than expected prevalence of diabetes was demonstrated among female subjects aged 30-54 years. Yersinia enterocolitica infection constitutes a differential diagnosis in acute pancreatitis, and might be related to the development of chronic pancreatitis and diabetes. PMID- 1602291 TI - Aspirin to prevent growth of vegetations and cerebral emboli in infective endocarditis. AB - The incidence of stroke on cranial computed tomography (CT) and change in echocardiographic vegetation area was prospectively compared in a preliminary observational study involving nine patients with infective endocarditis randomized to either low-dose aspirin (75 mg d-1, Group I, n = 4) or no aspirin (Group II, n = 5). Two symptomatic cerebral infarcts and one myocardial infarct occurred in the controls, compared to no events in patients on aspirin during a total observation period of 343 d (range 28-49 d). The mean vegetation area decreased in the aspirin group (mean change = -0.24 cm2), compared to an increase in controls (mean change = +0.35 cm2). The platelet half-life (normal range 5-6 d), which was measured using Indium-111 radiolabelling, tended to be lower in Group II (4.6 +/- 0.2 vs. 3.9 +/- 0.5 d). No side-effects or complications attributable to aspirin were observed. A possible role for adjunctive aspirin therapy in the prevention of embolic complications in infective endocarditis is suggested, and warrants further study. PMID- 1602292 TI - Elevated serum transcobalamin levels in anaemia of rheumatoid arthritis: correlation with disease activity but not with serum tumour necrosis factor alpha and interleukin 6. AB - Transcobalamin (TCII) and haptocorrins (TCI and III), tumour necrosis factor alpha (TNF), interleukin-6 (IL6) and parameters of disease activity were assessed in 20 rheumatoid arthritis (RA) patients without anaemia and 19 subjects with anaemia of chronic disease (ACD) in order to determine if there was a possible correlation between these parameters. TCII, TNF and IL6 correlated positively with RA disease activity parameters, whereas their serum levels were higher in the ACD patients. TC levels were not correlated with cytokine levels. Vitamin B12 serum levels were lower in ACD. We conclude that in RA, elevated serum TCII levels are possibly mediated by increased RA disease activity, but probably not by actions of TNF or IL6. Increased TCII levels found in ACD may be explained by the higher degree of RA activity in these patients, and could also be viewed as a compensatory reaction to anaemia or reduced vitamin B12 levels. However, these preliminary findings require further confirmation. PMID- 1602293 TI - Ketoprofen and ergotamine in acute migraine. AB - The objectives of this study were to evaluate and compare the efficacy and tolerability of ketoprofen and ergotamine in the treatment of acute migraine attacks without aura. The study design was a single-centre, double-blind, placebo controlled, cross-over comparison of a single dose of ketoprofen (100 mg) and ergotamine (2 mg) suppositories in the treatment of acute migraine attacks. Fifty patients were included in the statistical evaluation. Ketoprofen was found to be more efficient than ergotamine and placebo in reducing the severity of pain. Ketoprofen was found to be more satisfactory than ergotamine and placebo with regard to influence on working ability, and better than placebo in global assessment. We conclude that ketoprofen (100 mg suppository) is superior to ergotamine (2 mg suppository) and placebo in the symptomatic treatment of acute migraine attacks, and has better tolerability. PMID- 1602294 TI - Ketotifen--a therapeutic agent of eosinophilic fasciitis? AB - A 30-year-old male with eosinophilic fasciitis (EF) associated with morphoea and vitiligo is described. The patient showed a partial response to prednisone, but did not respond to hydroxychloroquine, D-penicillamine and cimetidine. In the light of reports of increased plasma histamine levels, and a putative role of mast cells in the pathogenesis of EF, ketotifen (a mast cell stabilizer) was prescribed. This non-toxic drug has allowed the patient to continue hard physical labour without further relapses and without corticosteroid therapy. PMID- 1602295 TI - Protracted cholestasis probably induced by oral contraceptive. AB - The case of a patient with intrahepatic cholestasis, probably induced by an oral contraceptive agent, is reported. Initially, early primary biliary cirrhosis was suspected, but this diagnosis could not be verified either clinically or by immunological tests. Re-examination and re-evaluation of the liver biopsy revealed some eosinophilia and sinusoidal dilatation, changes indicative of drug induced liver injury. The cholestasis gradually disappeared as indicated both biochemically and histologically, but the elevation of serum alkaline phosphatase levels persisted for some 10 years after termination of drug therapy. Oral contraceptive agent-induced jaundice or cholestasis is generally reported to disappear when the drug is stopped, and we are unaware of similar cases in the literature with a protracted course such as that described here. Still, the circumstances of this patient suggest that a correlation between the oral contraceptive agent and the hepatic reaction is most likely, and we consider it important that colleagues pay attention to this possibility. PMID- 1602296 TI - Hepatotoxicity due to repeated intake of low doses of paracetamol. AB - The cases of two patients with fulminant hepatic failure after intake of therapeutic doses (4-8 g) of paracetamol, and who were admitted to hospital for assessment for liver transplantation, are described. In both patients starvation, due to abdominal pain, nausea and vomiting or diarrhoea, was probably contributing to the toxic effect of the drug. One of the patients also had an excessive alcohol intake. Paracetamol should not be prescribed for patients with alcoholism or with low food intake. PMID- 1602297 TI - Copper coordination chemistry: bioinorganic perspectives. A symposium. August 3 7, 1992, Baltimore, MD. Abstracts. PMID- 1602298 TI - Isolation, purification, and cytotoxicity of 5-methoxypodophyllotoxin, a lignan from a root culture of Linum flavum. AB - A method has been developed for the large scale isolation of 5 methoxypodophyllotoxin [1] from a high-producing root culture derived from Linum flavum. A closely related lignan, 5'-demethoxy-5-methoxypodophyllotoxin [2], was also present in the root culture and was the cause of the main isolation difficulties. Essential steps in the isolation procedure are CH2Cl2 and XAD-4 extraction and XAD-8 cc followed by Si gel chromatography, using two different mobile phases. The isolated 5-methoxypodophyllotoxin [1] was very pure (greater than 99%) and possessed the desired stereochemical configuration, namely (-)-5 methoxypodophyllotoxin [1]. The in vitro cytotoxicity of 5-methoxypodophyllotoxin [1] against EAT and HeLa cells was determined and compared with those of podophyllotoxin [3], etoposide (VP-16-213) [4], teniposide (VM-26) [5], and 5 methoxypodophyllotoxin-4-beta-D-glucoside [6]. It appeared that 5 methoxypodophyllotoxin [1] has about the same cytotoxic potency as podophyllotoxin [3]. PMID- 1602299 TI - Westiellamide, a bistratamide-related cyclic peptide from the blue-green alga Westiellopsis prolifica. AB - The isolation and structural elucidation of westiellamide [1] from the terrestrial blue-green alga Westiellopsis prolifica is described. This moderately cytotoxic cyclic peptide appears to be identical with a bistratamide-type marine natural product from the aplouso-branch ascidian Lissoclinum bistratum. PMID- 1602300 TI - Studies on iridoids of tissue cultures of Penstemon serrulatus: isolation and their antiproliferative properties. AB - Penstemide and serrulatoloside as well as penstemide aglycone and serrulatoloside aglycone were isolated and identified in the calli and suspension cultures of Penstemon serrulatus. The influence of serrulatoloside, penstemide, and its aglycone on the spontaneous proliferation of mouse spleen lymphocytes or hepatoma cells in the Syrian hamster has been estimated in vitro. It has been found that these compounds produce a dose-dependent inhibition of [3H]-thymidine incorporation into the DNA of the examined cells. PMID- 1602301 TI - Biologically active gamma-lactones and methylketoalkenes from Lindera benzoin. AB - Brine shrimp lethality-directed fractionation of the 95% EtOH extract of ripe berries from Lindera benzoin led to the isolation of three new C21 alkane-alkene gamma-lactones designated isolinderanolide, isolinderenolide, and linderanolide as well as the known series of C17 and C19 obtusilactones (isoobtusilactone A, obtusilactone A, isoobtusilactone, and obtusilactone) previously isolated from Lindera obtusiloba. The novel (6Z,9Z,12Z)-pentadecatrien-2-one, the known (6Z,9Z) pentadecadien-2-one, and the known (+)-(Z)-nerolidol were also isolated as bioactive compounds. The structural elucidation and biological activities of these compounds are reported. PMID- 1602302 TI - Anti-AIDS agents, 4. Tripterifordin, a novel anti-HIV principle from Tripterygium wilfordii: isolation and structural elucidation. AB - A new kaurane-type diterpene lactone, tripterifordin [1], has been isolated from the roots of Tripterygium wilfordii. The structure of 1 was elucidated by spectroscopic methods, including the concerted application of a number of 2D nmr techniques that involved the 1H-1H COSY, heteronucleus-detected variants of the heteronuclear chemical shift correlation (HETCOR), phase-sensitive NOESY, and long-range HETCOR. Compound 1 shows anti-HIV replication activity in H9 lymphocyte cells with an EC50 of 1 microgram/ml. PMID- 1602303 TI - Novel sulfated oligosaccharides from the sea cucumber Cucumaria frondosa. AB - The structures of a novel sulfated saponin, frondoside B (C59H92O31S2M2) [5], and frondecaside (C58H92O63S6M6) [6], a unique hexasulfated decasaccharide, have been deduced by nmr (500 MHz) methods. Based on 1H COSY, relay COSY, NOESY, and 13C nmr data, frondoside B was shown to have the structure 3 beta-O-(3-O-methyl-beta D-glucopyranosyl-(1----3)-O-beta-D-6- sulfonatoglucopyranosyl-(1----4)-O-[beta-D xylopyranosyl-(1----2)] -O-beta- D-quinovopyranosyl-(1----2)-O-beta-D-4 sulfonatoxylopyranosyl++ +)-holost-7-ene sodium (or potassium) salt. From 1H COSY, relay COSY, 13C-nmr data, T1 measurements, and comparison with nmr spectra of frondoside B, the structure of frondecaside was established as 3-O-methyl-6 sulfonato-beta-D-glucopyranosyl-(1----3)-O-beta-D-6- sulfonatoglucopyranosyl-(1-- -4)-O-[beta-D-xylopyranosyl-(1----2)] -O-beta- D-quinovopyranosyl-(1----2)-O-beta D-4-sulfonatoxylopyranosyl++ +-(1----1)-3-O- methyl-6-sulfonato-beta-D glucopyranosyl-(1----3)-O-beta-D-6- sulfonatoglucopyranosyl-(1----4)-O-[beta-D xylopyranosyl-(1----2)] -O-beta- D-quinovopyranosyl-(1----2)-O-beta-D-4 sulfonatoxylopyranoside+ ++ sodium (or potassium) salt. PMID- 1602304 TI - Multiple sclerosis and vitamin B12 metabolism. PMID- 1602305 TI - The natural history of multiple sclerosis: a regional study with some longitudinal data. AB - A regional survey of multiple sclerosis (MS) patients in Wellington, New Zealand in 1983 identified 245 patients, giving a prevalence (all categories included) of 72 per 100,000. Retrospective review of the history and medical records identified a poorer prognosis for disability where there was progressive onset of symptoms, secondary progression after a remitting phase, older age of onset (40 years or more), or a motor syndrome involving the limbs at presentation. In 1983 follow up data were obtained on 96 patients who were seen during a previous survey in 1968. For those with definite or probable MS, progression to severe disability (Kurtzke disability status scale (DSS) 6-9) or death (DSS 10) was seen in 26/34 with moderate disability (DSS 3-5) in 1968 and in only 5/29 with mild disability (DSS 0-2). When the analysis is confined to those with symptoms for at least five years in 1968, severe disability or death from MS occurred in 22/30 with moderate and 4/19 with mild disability (chi 2 = 10.8, p = 0.001). It is concluded that the patient's established disability level after five years of illness is a useful, but not infallible, prognostic indicator. From the follow up of the 1968 patients, the probability of MS-related mortality for a given disease duration was calculated. Using this survival distribution to adjust the disability ratings in the 1983 population, it was found that the proportion with mild disability decreased steadily with increasing disease duration, reaching 14% when the disease duration was more than 25 years. PMID- 1602306 TI - Predicting the outcome of acute stroke: prospective evaluation of five multivariate models and comparison with simple methods. AB - Five multivariate models designed to predict the outcome of stroke were tested prospectively on 102 consecutive stroke patients admitted to a district general hospital. The results were compared with predictions made using two simple clinical variables (the conscious level on admission and the state of urinary continence at four weeks). Of the three models (developed in Belfast, Guy's Hospital and Uppsala) intended for use in the acute stages of stroke the last two were slightly more accurate in their prediction of death (75%) than was the admission conscious level alone (65%), whereas the Belfast model had an accuracy of only 50% in this situation. At a later stage, the state of urinary continence predicted good and poor outcomes with similar accuracy to that of a multivariate model from Edinburgh. A model developed in Bristol performed poorly. When tested prospectively, these multivariate models proved considerably less accurate than when they were first described. Only the Uppsala model showed any advantage over simple clinical methods. This might be of value in defining prognostic strata for clinical studies, but not in the management of individual patients. Simple clinical variables thus offer as much to clinicians as complex multivariate models. PMID- 1602307 TI - Spasticity and white matter abnormalities in adult phenylketonuria. AB - A 19 year old male with phenylketonuria (PKU) developed a spastic paparesis 8 months after stopping his restricted phenylalanine diet. CT and MRI showed abnormalities of the deep cerebral white matter, and visual evoked response latencies were prolonged. The spasticity gradually improved over several months after resuming the PKU diet. A repeat MRI scan was unchanged. His brother also had PKU and ceased dietary restrictions, but his only neurological abnormality was a slight increase in the deep tendon reflexes of the lower limbs. CT and MRI of his brain was normal. DNA analysis showed that both brothers were homozygous for the same PKU mutation. These patients demonstrate that reversible neurological signs may develop in patients with classic PKU after ceasing dietary restrictions and that these may be associated with abnormalities seen on neuro imaging. PMID- 1602308 TI - Cerebral correlates of disturbed executive function and memory in survivors of severe closed head injury: a SPECT study. AB - Thirty six patients in the chronic stage after severe closed head injury were examined with tests of executive function, memory, intelligence, and functional capacities in daily living. Correlations were sought between test results and Tc 99m-HMPAO uptake of frontal, temporal, and thalamic regions assessed by SPECT. Neither the number of significant correlation coefficients between memory tests and regional uptake nor that between temporal uptake and tests exceeded chance. For the remaining tests, correlations to thalamic regions were stronger than those to the frontal regions, and those to right brain regions stronger than those to homologous left brain regions. Relationships of thalamic isotope uptake to neuropsychological performance may reflect the impact of diffuse brain damage and particularly of diffuse axonal injury on mental capacities. PMID- 1602309 TI - A new variant of blepharospasm. AB - Ten patients who were unable to initiate or sustain eye opening in the absence of overt spasm of the orbicularis oculi, were investigated. In five, the problem was isolated. Three had Parkinson's disease and two progressive supra-nuclear palsy for between one to six years before the eye opening difficulty developed. The clinical features and electrophysiological investigation suggested that the disorder is a variant of blepharospasm due to abnormal contraction in the pre tarsal orbicularis oculi. PMID- 1602310 TI - Assessment of quality of life in patients treated for low-grade glioma: a preliminary report. AB - In this pilot study quality of life was assessed in fourteen adult patients who were treated for a low-grade glioma with surgery and radiotherapy at least one year previously. Apart from widely used parameters, such as the neurological and functional status, the patients' cognitive functioning and actual affective status were determined. In addition the patients were interviewed to evaluate various aspects of quality of life. Generally no serious focal neurological deficits were found, although psychological examination showed serious cognitive and affective disturbances in most cases. Self report measures concerning cognitive functioning were not in all cases in accordance with objective test results. When the results of treatment in glioma patients are evaluated assessment of quality of life, including neuropsychological functioning, should be performed, especially as new therapeutic strategies are being developed. PMID- 1602311 TI - A prospective longitudinal study of depression, cognitive decline, and physical impairments in patients with Parkinson's disease. AB - A consecutive series of 105 patients with Parkinson's disease were examined for the presence of affective disorders, cognitive deficits, and impairments in activities of daily living (ADLs); 92 received the same evaluation 12 months after the initial examination. On the basis of the initial psychiatric findings, patients were divided into major, minor, and non-depressed groups. Patients with major depression showed a significantly greater cognitive decline, deterioration in ADLs, and further advance through the Hoehn and Yahr stages than patients with either minor depression or no depression. PMID- 1602312 TI - Psychiatric morbidity in patients with peripheral vestibular disorder: a clinical and neuro-otological study. AB - This study reports the psychiatric morbidity in 54 patients with objective evidence of peripheral vestibular disorder seen three to five years after their original referral. A third of the patients were free from vestibular symptoms at follow up and a further third had experienced some improvement. Two thirds of the patients had experienced psychiatric symptoms during this period, although only 50% were rated above the cut off point for significant psychiatric disturbance when interviewed. Panic disorder with or without agoraphobia and major depression were the commonest psychiatric diagnoses. Patients with classical "labyrinthine" symptoms had a more severe canal paresis than the rest, but the degree of the abnormalities in the neuro-otological tests was unrelated to outcome or to psychiatric morbidity. On the other hand, there was a significant correlation between the presence of vestibular symptoms and psychiatric morbidity, which in turn correlated with measures of anxiety, perceived stress and previous psychiatric illness. PMID- 1602313 TI - A case of neurofibromatosis 2 presenting with a mononeuritis multiplex. AB - A patient with neurofibromatosis 2 had an asymmetrical peripheral neuropathy. A nerve biopsy specimen revealed neurofibromatous changes, and the neuropathy may have been a direct consequence of neurofibromatosis. An apparent clinical response to immunosuppressive treatment and plasma exchange is also reported. PMID- 1602314 TI - Uncoupling between CBF and oxygen metabolism in a patient with chronic subdural haematoma: case report. AB - The regional cerebral blood flow (rCBF) and oxygen metabolism of a patient with a chronic subdural haematoma were examined quantitatively, using positron emission tomography (PET). Before operation, the rCBF was decreased slightly throughout the brain, whereas the regional oxygen extraction fraction (rOEF) was increased throughout the brain, with values ranging from 0.36 to 0.60. One month after operation, the rCBF had recovered remarkably in almost all regions and rOEF had decreased to within the normal range. PMID- 1602315 TI - Congenital oculo-bulbar palsy. AB - A girl developed progressive weakness of bulbar and ocular muscles starting before the age of two years. Electromyography revealed a widespread subclinical myopathy. An intercostal muscle biopsy showed complex abnormalities including occasional neurofilamentous accumulations and honeycomb-like membranous material in terminal axons. Endplates were small and some secondary synaptic clefts were abnormally deep. Acetylcholine receptors extended unusually deeply into the clefts of the junctional folds. Muscle fibres showed subsarcolemmal vacuolation at some places. This form of congenital oculo-bulbar palsy does not appear to have been described previously. PMID- 1602316 TI - McArdle's disease with late-onset symptoms: case report and review of the literature. AB - McArdle's disease with late-onset symptoms is an unusual cause for muscle disease in older patients. The case of a patient with McArdle's disease whose symptoms began at 60 years of age is presented, and seven previous cases of late-onset McArdle's disease reported since 1963 are discussed. In five of the eight patients, the clinical presentation was similar to the early onset disorder with exercise intolerance, cramps, and myoglobinuria. In contrast, the remaining three patients presented with fixed proximal limb and bulbar weakness. Electromyography confirmed a myopathic process in four of four patients. Results of the forearm ischaemic exercise test were positive in seven of seven patients with complete myophosphorylase deficiency; results of muscle biopsies were diagnostic in all patients. McArdle's disease with late-onset symptoms is rare and clinically more variable than the early onset disorder. PMID- 1602317 TI - Occipital neuralgia: another benign cause of "thunderclap headache". PMID- 1602318 TI - Pure sensory Guillain-Barre syndrome. PMID- 1602319 TI - Cerebral venous thrombosis in paroxysmal nocturnal haemoglobinuria. PMID- 1602320 TI - Toxic reaction following the combined administration of fluoxetine and phenytoin: two case reports. PMID- 1602321 TI - Gamma vinyl GABA in the treatment of levodopa-induced dyskinesias in Parkinson's disease. PMID- 1602322 TI - Hypochromia iridis in acquired Horner's syndrome. PMID- 1602323 TI - Acute dystonia due to amitriptyline. PMID- 1602324 TI - Paradoxical akinetic response to apomorphine in parkinsonism. PMID- 1602325 TI - Proceedings of the Association of British Neurologists and the Liaison Psychiatry Group, Royal College of Psychiatrists. April 2-3, 1992. Abstracts. PMID- 1602326 TI - The legislative status of nurse-midwifery. Trends and future implications. PMID- 1602327 TI - Ernestine Wiedenbach. Her professional legacy. AB - A descriptive, historical research study of the life and career path of Ernestine Wiedenbach was conducted. A productive career spanning five decades included accomplishments in prepared childbirth education, family-centered maternity care, nurse-midwifery education, and nursing theory. Wiedenbach's prescriptive theory of nursing with its focus on "clarity of central purpose" stands out as an important early professional achievement of this practitioner, educator, author, and theorist. It represents one of Wiedenbach's many pioneer contributions to nursing as well as to the foundation of the philosophy and goals of nurse midwifery practice and education. PMID- 1602328 TI - The genesis of the ACNM 1971 Statement on Abortion. AB - In 1971, the Board of Directors of the American College of Nurse-Midwives approved a statement that prohibited certified nurse-midwives (CNMs) from performing abortions. In 1990, the statement was superseded by a second "Statement on Abortion," which essentially reworded the 1971 statement with no substantive change. In 1991, 20 years after the first statement was adopted, a resolution was approved at the Annual Meeting recommending that the Board of Directors rescind the statement, thereby allowing individual CNMs to utilize the guidelines for the incorporation of new procedures into nurse-midwifery practice if she/he decides to provide abortions. This article describes the historical basis for the initial 1971 statement in the hope that an understanding of that history will assist nurse-midwives as they reconsider the statement. PMID- 1602329 TI - Nurse-midwifery today. A legislative update. Part II. PMID- 1602330 TI - Chlamydia infection in a nurse-midwifery caseload. AB - The purpose of this study was to determine whether antepartum treatment of chlamydia infection resulted in a change in incidence of maternal infection in the intrapartum and postpartum periods as indicated by the incidence of maternal febrile morbidity or antibiotic therapy. In June of 1986, an inner-city tertiary care center nurse-midwifery service began including diagnosis and treatment of chlamydia infection in routine antepartum care. In this retrospective chart review, the incidence of intrapartum and postpartum infection among women who delivered in this caseload between May 1985 and May 1986 (the last year prior to the routine chlamydia diagnosis and treatment) was compared with that of women who delivered between July 1986 and July 1987 (the first year after initiation of the testing). No significant differences were found. Implications for the development of research projects within nurse-midwifery clinical services are discussed, along with methodologic problems that may ensue when attempting to study changes in outcome in ones' own service. PMID- 1602331 TI - Vena caval filter use in orthopaedic trauma patients with recognized preoperative venous thromboembolic disease. AB - This study comprises a series of 35 patients with pelvic or lower extremity fractures requiring surgery who also had a documented significant acute deep venous thrombosis (DVT). The authors treated these with low-dose Coumadin and 36 vena caval filters, which were used prophylactically prior to surgery. The patients received low-dose warfarin after placement of the vena caval filters and were maintained at 1.3-1.5 times the prothrombin control value for 6 weeks to 3 months. In this group of patients, there were no fatal pulmonary emboli and no clinically significant complications from filter placement. There were nine asymptomatic filter complications demonstrated radiographically in eight patients. Additionally, one patient with a tilted vena caval filter required placement of another filter. The combination of vena caval filters and low-dose warfarin appears to be a successful and relatively safe method of managing those patients who have acute DVT and require surgery for their pelvic or lower extremity fractures. PMID- 1602332 TI - Greenfield filter prophylaxis of pulmonary embolism in patients undergoing surgery for acetabular fracture. AB - Pulmonary embolism is a potentially lethal complication among patients with acetabular fractures requiring surgery. The reliability, safety, and extent of efficacy of pharmacologic as well as existing nonpharmacologic anticoagulation prophylaxis in this patient group has not been determined. A careful analysis of the myriad factors acting on these patients who have had major trauma and have undergone a major surgical procedure about the hip prompted a change in our approach to prophylaxis in this patient group. In the period from March 1984 through October 1987, 51 patients having 52 acetabular fractures underwent osteosynthesis at the Wake Forest University Medical Center. Twenty-four patients had two or more identifiable risk factors and underwent insertion of a Greenfield filter for prevention of pulmonary emboli. Filters were inserted at the time of acetabular surgery with C-arm guidance via the internal jugular vein approach. The average time for insertion was 57 min. Placements were verified by plain roentgenograms. There were no complications during filter insertion. Four patients with filters (17%) developed leg edema; in three the edema was minor, and in one the filter trapped what could have been a fatal embolus but caused lower extremity venous stasis severe enough to result in peripheral lower extremity tissue loss. There were no pulmonary emboli (by clinical criteria). The remaining 27 patients had routine medical prophylaxis and no filters. In this group, two patients had a clinically evident pulmonary embolus (7%), and one of these patients died. Two other patients (7%) had minor chronic leg edema. In one of them, a proximal deep venous thrombosis in the lower extremity was documented with venography, requiring rehospitalization and anticoagulant therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602333 TI - Danger zone of the acetabulum. AB - The danger zone of the acetabulum is defined by Marvin Tile as that part of the posterior wall and column at the mid-acetabulum lying above the ischial spine. Screws inserted in the danger zone are at risk of violating the hip joint. Unfortunately, this zone is frequently used in the fixation of posterior wall and column fractures. Cadaveric studies were performed analyzing 1-cm cross-sections through the acetabulum for the purpose of studying the anatomical configuration of the danger zone. The plane of the cross-section was perpendicular to the posterior column. Each cross-section had the medial boundary of the acetabulum projected onto the posterior column. The cross-sections were then assembled to form the original acetabulum. By analyzing the projections on the posterior column, the exact configuration of the danger zone was determined. Screws placed at the margin of the danger zone and directed perpendicular to the posterior column violated the hip joint. Through analysis of the cross-sections, safe anatomic pathways were developed for screw placement. Cortical screws (4.5 mm), placed at entry points of 2 cm and 3 cm medial to the lateral acetabular margin and angled medially 45 degrees and 15 degrees, respectively, did not violate the hip joint. The angulation was respective to the perpendicular to the posterior column. In this study, the average width of the posterior column at the mid acetabular level was 4.8 cm. Computed tomography scan of the acetabulum yielded valuable information regarding screw placement in the posterior column.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602334 TI - Factors influencing postoperative movement in displaced femoral neck fractures: evaluation by conventional radiography and stereoradiography. AB - Postoperative movement in 46 displaced femoral neck fractures was studied using roentgen stereophotogrammetric analysis (RSA). Thirty-four fractures became stable, all within 1 year. Measurements on pre- and postreduction radiographs and scintimetry were performed to evaluate factors of importance in healing, redisplacement, and nonunion. Thirty-three fractures were treated with two hook pins with (7 cases) or without (26 cases) a plate, and 13 were treated with two cancellous screws. Presence of intermediate fracture fragments and fixation with two screws implied increased movement of the femoral head center during the postoperative period. Remaining ad latus displacement on the anteroposterior or lateral view after reduction of more than 1 mm and low scintimetric uptake implied increased risk of redisplacement or pseudarthrosis. Increased displacement of the femoral head center during the first postoperative month was recorded in fractures that did not heal. The magnitude of the femoral head rotations did not differ between the implants, but smaller screw axis rotations were noted in fractures that subsequently healed. In most hips fixated with screws, the instant center of femoral head rotation went through the femoral head or neck, whereas hook-pin fixation more commonly was associated with screw axis position within or close to the trochanteric region, suggesting a more durable fixation in the femoral head of this device. PMID- 1602335 TI - Ipsilateral fractures of the femoral neck and shaft. AB - Thirty-three patients with ipsilateral intracapsular femoral neck and shaft fractures were treated with antegrade reamed intramedullary (IM) nails and cancellous screw fixation of the femoral neck. The shaft fractures were fixed prior to definitive neck stabilization. A "reversed" nail construct was used in 13 patients, a conventional interlocked nail was used in 6, and a reconstruction nail was used in the remaining 14. Thirty-one (94%) of the femoral shaft fractures healed primarily. In two patients, the shaft fracture failed to unite and was bone grafted and plated, respectively; the fractures subsequently healed. However, only 27 (82%) of the femoral neck fractures healed after initial fixation. In six patients (18%), a symptomatic varus nonunion developed, requiring a valgus osteotomy. Five of the six femoral neck non-unions and all of the osteotomy sites united; however, two of these patients later developed osteonecrosis of their femoral heads. Closed reamed antegrade IM nailing with supplemental screw fixation of ipsilateral femoral neck and shaft fractures did not produce uniformly successful results because of high rates of varus nonunion of the femoral neck fracture. PMID- 1602336 TI - Patterns and complications of femur fractures below the hip in patients over 65 years of age. AB - This study is a retrospective review of 105 femur fractures below the hip in 99 patients over 65 years of age treated between 1970 and 1986. Problems in medical management and a high complication rate prompted this study, which focused on the fracture patterns and complications associated with these injuries. There were 25 subtrochanteric, 47 shaft, and 33 supracondylar fractures. These were isolated injuries in 89 of the patients. The overall complication rate was 45%; the orthopaedic complication rate was 15%. The mortality rate was 10% within 60 days of injury. Thirty-nine patients (39%) returned to their preinjury functional status or were able to walk with ambulatory assistive devices. Changes in mental status before fracture were associated with an increased rate of complications. Age, sex, preinjury functional status, number of preexisting medical problems, timing of surgery, type of anesthesia, and operative versus nonoperative treatment were not significantly different between survivor and nonsurvivor groups. The development of a new, postinjury medical problem in the acute treatment period was the most significant factor leading to a poor result and death. Successful management of this fracture requires aggressive medical management in the elderly. PMID- 1602337 TI - Blood loss and transfusion in patients with isolated femur fractures. AB - A retrospective study of 53 patients with isolated femur fractures was performed to evaluate blood loss and transfusion incidence. Patients with other long bone fractures, abdominal, chest, mediastinal, and vascular injuries were excluded. Twenty-one patients required transfusion during the initial hospitalization averaging 2.5 units PRBCs. Admission hematocrit, preoperative and total EBL were found to be significant variables in determining transfusion. Fracture patterns, classified as high or low energy, were not found to correlate with pre- or intraoperative blood loss, incidence of transfusion, delay to surgery or duration of hospital stay. The estimated blood loss in the study group averaged 1,276 cc, stressing the significance of long bone fractures in trauma patients. Preoperative hemorrhage determined transfusion need in contrast to intraoperative blood loss. PMID- 1602338 TI - Major vascular lesions associated with orthopaedic injuries. AB - Seventeen patients, aged 11-67 years (mean, 32.6), with major vascular injuries associated with traumatic orthopaedic injuries, were treated operatively in the authors' institution over a 4-year period. The most common mechanism of trauma was a high-energy injury (70.8%), and the rate of open injuries was 88.2%; 64.9% of the injuries were located in the lower extremities. The treatment protocol consisted of aggressive resuscitation; Doppler imaging and, when necessary, angiography; stable bone fixation with subsequent vascular repair; and extended wound debridement. The vascular repair for arterial lacerations consisted of (a) end-to-end anastomosis (47.2%); (b) interpositional homologous vein graft (23.6%); (c) vascular decompression through fracture distraction in one patient (5.9%); (d) xenograft interposition (in one patient; 5.9%); (e) venous repair (in three patients; 17.7%); and (f) embolectomy (in all patients). Three vascular reoperations (17.7%) were necessary because of rupture of the anastomosis. The authors' preferred bone stabilization method was external fixation, which was used in 47.2% of cases. Amputation was performed in three cases (17.7%) as a salvage operation. Although six patients (35.4%) were admitted with delayed shock (mean duration, 73.6 +/- 27.8 min), this led to a lethal outcome due to shock lung in only one patient. Another patient developed massive lung embolism 3 months postoperatively and died. The authors believe that this well-organized approach, based on a specific treatment protocol, for patients with severe orthopaedic trauma and concomitant vascular injury, not only improves outcome but gives good to excellent functional results in the majority of patients. PMID- 1602339 TI - Soda pop vending machine injuries: an update. AB - Soda pop vending machine tipping continues to be a dangerous behavior that can result in lethal or crippling injuries. This study analyzes 64 cases of injuries secondary to crushing by a soda machine. All were male victims except one. The average age was 19.8 years with a range of 5-39 years. Thirteen victims sustained multiple trauma. Fifteen victims were killed. Increased public awareness coupled with support by the government and private industry has contributed to a sharp reduction in incidence of accidents and improved public safety. PMID- 1602340 TI - An investigation of the contribution of the extraosseous tissues to the diaphyseal fracture callus using a rabbit tibial fracture model and in situ immunocytochemical localisation of osteocalcin. AB - The extraosseous tissue contribution to diaphyseal fracture callus has been investigated using a rabbit tibial fracture model and osteocalcin immunocytochemistry. The extraosseous tissues were isolated for study by reaming and nailing an osteotomy and excising 2 cm of periosteum on either side of the osteotomy. Specimens obtained from the healing fractures at 1 and 2 weeks after operation, respectively, were decalcified and stained for osteocalcin, a bone specific protein, using an indirect immunoperoxidase method. The positively stained osteogenic cells appeared to be derived exclusively from the remnant of the periosteum. PMID- 1602341 TI - Complications encountered in the treatment of pilon fractures. AB - A total of 52 tibial plafond (pilon) fractures in 51 patients were retrospectively reviewed from the years 1985-1990 to define the rate of complications encountered during their management. All fractures were managed under faculty supervision at a level I trauma center and its two affiliated institutions. The follow-up period was scrutinized to determine whether or not a complicating event occurred. Major local complications, termed events, were defined as those requiring unplanned surgery due to infection, wound breakdown with subsequent flap coverage, and failure of fixation or fracture healing. Reduction accuracy and final clinical results were not specifically examined. There were 14 (27%) type I, 17 (33%) type II, and 21 (40%) type III Ruedi Allgower fracture types. The majority (79%) of the fractures were closed and 89% were treated by open reduction and internal fixation. The overall local complication rate was 54%. A total of 21 (40%) pilon fractures (six type I, six type II, and nine type III) had major local complicating events requiring 77 additional operations. Patient follow-up time ranged from 1 week (the occurrence of a major local complication) to 200 weeks (no complication), with a mean of 67 weeks. Kaplan-Meier survivorship (K-M) analysis was utilized to statistically estimate the complication rate in this patient population accounting for the occurrence of censored events. The K-M-determined event rate was 42 +/- 7%. Ten (of 21) pilon fractures had events by 3 weeks, while only two occurred beyond 40 weeks. PMID- 1602342 TI - The salvage of open grade IIIB ankle and talus fractures. AB - Between 1983 and 1989, 11 open grade IIIB ankle or talus fractures were treated according to protocol including debridement, temporary placement of antibiotic beads, soft tissue coverage (including seven free vascular tissue transfers), intravenous antibiotics and fusion using an anterior plate, and bone graft. All patients had a minimum of three separate hospitalizations. Each had at least five operative procedures performed with an average of 8.2/patient (range: 5-12). The total in-patient hospital stay averaged 61.6 days (20-107 days) and in patient costs averaged $62,174.43/patient (range: $33,535.06-$143,847.45). Overall hospital cost averaged $1,009.32/day. Follow-up averaged 47.8 months (range 32-85 months), with an average time to union of 4.4 months. Fusion rate and muscle flap success was 100%. Although fusion and eradication of infection in this specific group of patients was possible, significant functional and psychosocial disability remained. Eight of eleven patients had significant pain, difficulty with stairs, and limited ambulation. All changed jobs or were unemployed. Patients with open grade IIIB tibiotalar injuries with significant bone loss may therefore benefit from early amputation. A multicenter randomized clinical outcome study is needed. PMID- 1602343 TI - Solitary paralysis of the triceps muscle due to trauma. AB - We report a rare solitary paralysis of the triceps muscle. The patient, an 18 year-old man who had had a work-related accident, sustained a severe contusion of the proximal posterolateral arm after being struck by a piece of lumber. This injury produced an extraordinary amount of soft-tissue swelling in the region of the trauma. After the accident it was noted that active flexion of the elbow was preserved, but active extension was absent. Three months after injury, surgical exploration of the radial nerve and its rami musculares to the three heads of the triceps muscle was undertaken. Dense adhesions were found fixing the rami musculares to the surfaces of the triceps muscle. Neurolysis of the rami musculares was performed, leading to complete recovery of the triceps muscle. The etiology of this isolated paralysis of the triceps muscle was determined to be dense adhesions compressing and compromising the function of the rami musculares to the three heads of the triceps muscle. These adhesions formed because of severe posttraumatic bleeding into the potential posterior humeral space, where the rami musculares are found. PMID- 1602344 TI - Postoperative radial nerve paralysis caused by fracture callus. AB - This is a case of late-onset (6 weeks) radial nerve paralysis following open reduction and internal fixation of a comminuted distal humerus fracture. A transected radial nerve within the callus was found at reoperation. The mechanism of transection was thought to be repetitive motion of the nerve across an edge of new bone. The nerve was repaired and tendon transfers done subsequently with less than full functional recovery at 16 months. No such case has been previously reported. PMID- 1602345 TI - Capacitively coupled electrical field in the treatment of a leg fracture after total knee replacement. AB - Electrical stimulation has been used as treatment for nonunions of fractures since the early 1950s, with a reported success rate of 80-85%. We report a case of nonunion of a tibial fracture below a revised total knee prosthesis treated with a capacitively coupled electrical field. After 3 months of treatment, consolidation of this difficult fracture was evident with abundant callus formation. PMID- 1602346 TI - Prophylactic intramedullary fixation of the tibia for stress fracture in a professional athlete. AB - Prophylactic intramedullary nailing of the tibia for stress fracture was performed successfully in a professional football player, enabling him to resume his career. No similar case has been reported previously. PMID- 1602347 TI - Liquefaction and calcification of a chronic compartment syndrome of the lower limb. AB - We present an uncommon late sequela of a compartment syndrome of the leg that presented as liquefaction and calcification. Our experience with this clinical situation, along with the available literature review, suggests an approach to this diagnostic and therapeutic problem. We recommend that repeated needle aspiration be performed to lessen the risk of secondary infection, chronic sinus formation, and amputation, which may occur after debridement and drainage of the lesion. PMID- 1602348 TI - Fracture of the neck of the talus associated with a trimalleolar ankle fracture and ruptured tibialis posterior tendon. AB - A rare case of a fracture through the neck of the talus with a trimalleolar ankle fracture and ruptured tibialis posterior tendon is presented and the literature reviewed. Management consisted of open-reduction internal fixation of the fractures and repair of the tibialis posterior tendon. At 40 months after injury, the patient had tibiotalar range of motion at 5 degrees of dorsiflexion and 38 degrees of plantar flexion. While avascular necrosis of the talus did not occur, significant degenerative arthritis of the ankle was noted. PMID- 1602349 TI - Intra-articular fractures of the calcaneus: present state of the art. PMID- 1602350 TI - [The 93rd general meeting of the Japanese Society of Otolaryngology. Nagoya, May 15-17, 1992]. PMID- 1602351 TI - [Inner ear decompression sickness following a scuba dive]. AB - Inner ear decompression sickness (IEDCS) is one form of Type II decompression sickness. Most cases of IEDCS have been associated with saturation dives, so there are very few reports of occurrence following shallow scuba dives. We present here the case of a diver who suffered from IEDCS following a shallow scuba dive (30m), and was successfully treated by the protocol outlined in U.S. Navy treatment table 6. This case suggests that there is the possibility of occurrence of IEDCS, even following a shallow scuba dive, if proper decompression procedures are not adhered to. In addition, detailed analysis of diving profiles should be used to distinguish the inner ear dysfunction seen in some divers from inner ear barotrauma which may be attributable to IEDCS. PMID- 1602352 TI - [Three dimensional analysis of caloric nystagmus using computerized image recognition]. AB - Three-component analysis of caloric nystagmus, focusing on horizontal, vertical, and torsional directions, using a newly developed computerized eye movement analysis system was carried out in ten normal human subjects. The caloric response was induced by cold stimulation to the right ear while the subjects were in supine and prone positions. The directions of the three components of nystagmus, were left in ten subjects (10), upward (8) or downward (2), and clockwise (10) in the supine position. In the prone position, on the other hand, the three components were directed toward the right (10), downward (5), upward (3), and counterclockwise (10) or were not present (2). These findings indicate that caloric stimulation activates the three semicircular canals simultaneously. In addition the changes in the direction of nystagmus in the supine and prone positions could not be explained in detail by the convection theory of caloric response alone. PMID- 1602353 TI - [Effect of the rate of speech flow on speech intelligibility in normal and hearing-impaired subjects]. AB - The relationship between the rate of speech flow and speech intelligibility was investigated in normal and hearing-impaired subjects. It is usually observed that a slowly and clearly delivered speech is easier for hearing-impaired patients to understand. The purpose of paper is to analyze this phenomenon clinically and to present useful data for developing new hearing aids. Four or 5 syllabic words lists were prepared for this experiment and speech stimuli were chosen from these lists. The subjects consisted of 15 normal subjects and 79 hearing-impaired patients (57 with inner ear hearing loss and 22 with retrocochlear hearing loss). Hearing tests were performed using a tape recorder with various speech control systems in a soundproof room. Speech samples were presented at three speaking rates, that is, a conversational speech rate, a rate one and a half times as fast as the conversational speech rate and a rate twice as fast as that rate. The results obtained in the normal subjects confirmed that the faster the speaking rate was, the more the word intelligibility was reduced. According to the results in the hearing-impaired subjects, both the correlation coefficient and regression parameter between the word intelligibility in this experiment and speech discrimination scores measured by 57S-monosyllabic lists were low at the conversational speaking rate, but the higher the speaking rate was, the closer the relation between the both factors was. It was estimated by analyzing the data of inner ear hearing loss and retrocochler hearing loss separately that the subjects with retrocochler hearing loss had more difficulty in speech-mediated communication than the subjects with inner ear hearing loss. PMID- 1602354 TI - [Magnified tomography for identification of ceramic prostheses]. AB - Recently, ceramic prostheses for ossicular replacement have become very popular in middle ear surgery. These prostheses have a good affinity with the surrounding tissue. But, it is difficult to identify the position of these prostheses postoperatively. We used magnified tomography in order to identify the implanted ceramic prostheses, and to determine whether these prostheses were in the appropriate position. In the case of patients without stapes, we usually use Apaceram type T, which restores ossicular continuity to the inner ear. When the shaft of the ceramic prosthesis is placed on the oval window niche, the overhanging Fallopian canal obstructs the tip of the prosthetic shaft to obtain the appropriate place in the oval window. The angle of the shaft should be slightly tilted inferiorly against the medial wall of the middle ear cavity. PMID- 1602355 TI - [Immunological study of the HLA class II antigen associated with birch pollen allergy]. AB - Pollinosis is known as a hereditary disease. Recently, association of HLA antigens and pollinosis caused by several pollen allergens has been reported. Furthermore, HLA antigens are considered to have a very important role in the development of pollinosis. We performed an HLA population study and tested the lymphocyte proliferative response (LPR) to birch pollen allergens with birch pollen allergic patients and healthy control subjects. The results of the HLA population study indicated that HLA-DR9 and HLA-DQw3 correlated with the development of birth pollinosis (relative risk [R. R] = 6.37 for DR9 and R. R = 7.92 for DQw3). DNA typing revealed that serotype DQw3 in patients were DQw9 specific. Two sources of birch pollen allergens, betula pendula and betula platyla var. japonica, were used in LPR. Lymphocytes from the patients, but not from the healthy control subjects, proliferated in response to these two allergens. Anti-HLA-DR antibody, but not anti-HLA-DQ antibodies, inhibited the patients' LPR. These results suggest that the HLA-DR molecules are responsible to present the pollen specific antigen to T lymphocytes inducing LPR in the patients. Furthermore, in some of the healthy control subjects, anti HLA-DQ antibodies enhanced this LPR almost to the same level as that of the patients'. This result indicates that HLA-DQ molecules might be associated with the suppression of T cell proliferation. PMID- 1602356 TI - [Biopsy of head and neck lesions with a Biopty biopsy instrument]. AB - Recently, "Biopty-Gun" technique has been introduced as a new biopsy technique specially in urological field. We applied it to obtain histopathological specimens of head and neck lesions. 25 specimens were taken with 18-gauge needle, using ultrasonic guidance in cases where the targets were very close to arteries or very small or cystic lesions. All these 25 specimens could be obtained without any complication such as crushing of tissue and they were all sufficiently clear and high-quality specimens. In 23 of these 25 specimens, exact histopathological diagnosis could be made. "Biopty-Gun" minimizing possible movement of tissue which may often occur with the conventional biopsy technique, permitted obtaining tissue specimens without crushing or damaging cells of tissue to be sampled, and it was concluded to be a highly safe and useful biopsy procedure. PMID- 1602357 TI - [Susceptibility of organ of Corti with or without melanin to acoustic overstimulation]. AB - Albino and pigmented guinea pigs were compared in terms of susceptibility to acoustic trauma. The animals were exposed to a 4 kHz pure tone of 120 dB for 60 min. N1 thresholds of CAP were measured before and after the acoustic exposure. Changes in the outer hair cell and stria vascularis were studied using SEM and TEM. After acoustic trauma, N1 thresholds were more elevated in the albino than in the pigmented guinea pigs. Also, pathological changes in the outer hair cell and stria vascularis were more severe in the albino animals. A noteworthy finding in the stria vascularis was that the melanin in intermediate cells had moved into marginal cells. This melanin migration may be possibly involved in mechanisms underlying prevention of acoustic trauma. PMID- 1602358 TI - [Electron microscopic observations of the porcine middle ear--normal cases]. AB - Pigs are frequently used in basic studies of the middle ear because they have a middle ear air cell system which resembles the human mastoid air cell system. However, the morphology of epithelial cells of the middle ear of pigs has not been thoroughly studied. In this study, the morphological features of the mucosal epithelium of the normal porcine middle ear from juveniles to adults were investigated by scanning and transmission electron microscopy. The features were compared with the mucosal epithelium of the human middle ear. Macroscopic observation of the resected middle ears showed all normal. The mucoepithelial cells of the normal porcine middle ear consisted of ciliated cells, non-ciliated cells, secretory cells and basal cells. Ciliated cells were distributed most densely in the Eustachian tube and tube orifice of the middle ear cleft, decreasing in number towards the air cell system, where no ciliated cells were found. The distribution of secretory cells was similar to that of ciliated cells, while non-ciliated cells distributed conversely. Ciliated cells of juvenile pigs had 40 to 100 cilia 5 to 6 mu in length and 0.2 to 0.3 mu in thickness and microvilli on the cell surface. On the other hand, pigs 4 weeks old or older, had ciliated cells with 80 to 100 cilia 5 to 8 mu in length and 0.3 to 0.4 mu in thickness. Younger pigs had a smaller range of ciliated cell distribution. The range increased with growth, and rapidly expanded by 2 weeks after birth; then the expansion slowed down to 4 weeks, when the distribution was similar that in maturity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602359 TI - [Electron microscopic observations of the porcine middle ear--inflammatory changes]. AB - In previous studies, the morphology of the mucoepithelial cells of the middle ear of normal pigs has been found to be similar to that of humans. In this study, otitis media was induced in 18 ears by transcanal injection of glycerin into the middle ear cleft and morphological changes were investigated by scanning and transmission electron microscopy. The mucoepithelial cells of the inflamed porcine middle ear consisted of ciliated cells, non-ciliated cells, secretory cells and basal cells, and the distribution of these cells was similar to that of normal cases. In the inflamed Eustachian tube and middle ear cleft, the epithelial cells were detached, the intracellular junctions ruptured and there was subepithelial thickening in some places. In addition, the cilia were detached or deformed irregularly. On the other hand, ciliated cells, bulging non-ciliated cells, secretory cells and columnar cells were increased in numbers. These features suggested that the muco-ciliary system of the inflamed ears had been stimulated. In the air cell system, however, there were signs of mucoepithelial cell injury, but no evidence suggesting that the muco-ciliary system had been stimulated as in the Eustachian tube or middle ear cleft. The inflammatory changes in the mucoepithelial cells in the Eustachian tube and middle ear cleft gradually returned to normal but in the air cell system, the changes were persistent. Moreover, the signs of mucoepithelial cell injury remained longer when inflammation occurred at a younger age.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602360 TI - [Study on the origin of vestibular neurons projecting to the spinal cord using retrograde labelling technique of horseradish peroxidase]. AB - In spite of a large number of electrophysiological studies into the vestibulospinal (VS) effects on the spinal cord, there are far fewer anatomical studies on the VS projections. The present study was undertaken to determine the origins and descending pathways of VS neurons in the cat, using a retrograde labelling technique of horseradish peroxidase (HRP) combined with a lesion in the lower brainstem. HRP was applied unilaterally into the cervical or lumbar spinal cord and either the medial longitudinal fasciculus (MLF) or the lower medulla oblongata, sparing the MLF, was dissected. In all cases, HRP-labelled neurons were located in two distinct areas of the vestibular nuclear complex, the rostral and caudal areas. In the rostral area, HRP-labelled neurons after dissection of the MLF appeared in the ipsilateral lateral (LN), medial (MN) and descending nuclei (DN), on the same side as HRP insertion into the spinal cord, but somatotopical arrangement was not seen in the present study. Labelled neurons in the rostral part after impairment of a wide area of the lower medulla, though sparing the MLF, were seen bilaterally in the areas bordering the LN, MN, DN and superior nuclei. In the caudal area, HRP-labelled neurons were seen bilaterally in the caudal thirds of the MN and DN, and these projected to the lumbar spinal cord. Therefore the origins and descending pathways of the VS tracts were considered to be different from those shown in previous anatomical studies. PMID- 1602361 TI - Treatment of acyclovir-resistant herpes simplex virus infections in patients with AIDS. AB - Resistance to acyclovir in vitro in herpes simplex virus (HSV) isolates has been associated with failure of acyclovir therapy in immunosuppressed patients, and the frequency of reports of clinical resistance in patients with human immunodeficiency virus (HIV) infection is increasing. The primary mechanism of clinical resistance is mutation, producing deficiency in the virus-specified thymidine kinase. A number of case reports and patient series have suggested the efficacy of foscarnet in the treatment of acyclovir-resistant HSV infection in HIV-infected patients. In a recent AIDS Clinical Trials Group study comparing the efficacy of vidarabine and foscarnet in this indication, foscarnet therapy was found to be associated with statistically significant reductions in time to complete healing of lesions, cessation of viral shedding, and 50% reduction in pain, and all patients randomized to receive foscarnet had complete re epithelialization of lesions. The majority of initial recurrences of herpetic lesions in patients in this study were susceptible to acyclovir; however, all patients ultimately experienced a recurrence due to acyclovir-resistant HSV. A trial comparing acyclovir suppression, foscarnet maintenance therapy, and no chronic antiviral therapy after successful initial treatment of acyclovir resistant HSV infection would be useful in defining the optimal management of recurrent disease. PMID- 1602362 TI - Mental health care rights of adolescents: what mental health nurses need to know. AB - Adolescents have certain rights regarding mental health care. There is a need for healthcare professionals, including nurses, to become more aware and knowledgeable of these rights. This article reviews the medical/legal rights of adolescents and their parents, and presents a history of relevant changes that have occurred in the parent-child relationship. It discusses also current issues pertinent to the mental health care of adolescents and identifies researchable questions. PMID- 1602363 TI - Informed consent with children and adolescents. AB - Nurses are becoming increasingly responsible for obtaining consent from children and adolescents for psychiatric treatment. The current practice of obtaining consent for participation in research is discussed. Consent from minors has implications for clinical treatment. This article examines power and powerlessness, and restrictiveness of the treatment setting in relation to nurses obtaining consent from children and adolescents. PMID- 1602364 TI - Children's concepts of the mentally ill. AB - One hundred sixty-eight children in grades three through six were asked to read vignettes describing the problematic behaviors of mentally ill children and adults. The schoolchildren then labeled the characters, attributed causes and motivations to their behaviors, and suggested possible treatments. Although only 27% of the children labeled vignette characters as mentally ill and 11% recommended psychiatric interventions, all the children recommended some kind of intervention. While slightly fewer than one-third (29%) of the children suggested that an adult intervene in some nonpsychiatric manner, 60% recommended some kind of child-initiated activity as an intervention. A developmental trend was evident in children's attribution of mental illness labels and recommendations for both psychiatric and adult nonpsychiatric interventions. PMID- 1602365 TI - The challenge of ritualistic child abuse. AB - Survivors of ritual abuse have endured physical and psychosexual trauma typically compounded by mind-altering drugs. Some abused children have never known a trustworthy adult to protect them from harm. Children often cope with the anxiety and terror of abuse through psychological defenses such as denial, self-hypnosis, and dissociation, but more extreme responses such as self-mutilation or multiple personalities may occur. Reports of ritual abuse of children are so shocking and bizarre that professionals initially respond with confusion and disbelief (Cozolino, 1989). Nurses need to assess clues and detect symbols of abuse in drawings or flashbacks, to build trust, and to monitor their attitudes and countertransference. Nurses are in a critical position to detect and begin healing wounds of ritual abuse. PMID- 1602366 TI - Child maltreatment, stressful life events, and behavior problems in school-aged children in residential treatment. AB - This study examined the prevalence of child maltreatment, stressful life events, and behavior problems in school-aged children in residential treatment. The sample included 44 children, ages 5-13 years; 61% were male and 39% female. Results indicated that the entire sample had experienced one or more types of maltreatment, with physical abuse being more prevalent. Seventy-four percent of subjects scored in the clinical range on the Child Behavior Checklist (Achenbach & Edelbrock, 1983). Proportionally more physically abused children scored in the clinical range when compared to nonphysically abused children. The number of stressful life events experienced after admission to the treatment facility was found to be related to increased behavior problems. PMID- 1602367 TI - Supersensitization of the oral response to SKF 38393 in neonatal 6-OHDA-lesioned rats is mediated through a serotonin system. AB - To study possible interactions between dopamine (DA) and serotonin (5-HT) neurochemical systems in the D-1 supersensitized induction of oral activity in neonatal 6-hydroxydopamine (6-OHDA) lesioned rats, the effects of a series of 5 HT agonists and antagonists were determined. At 3 days after birth rats were treated with desipramine HCl (20 mg/kg i.p., base form, 1 hr) and 6-OHDA HBr (100 micrograms, salt form, in each lateral ventricle). Rats were observed individually as adults, once a minute every 10 min over a 1-hr period after challenge with a DA or 5-HT receptor agonist. The respective 5-HT1A and 5-HT1B agonists, (+/-)-8-hydroxydipropylaminotetralin (0.50 mg/kg s.c.) and CGS 12066B maleate (7-trifluoromethyl-4(4-methyl-1-piperazinyl)-pyrrolo[1, 2-alquinoxaline], 1:2 maleate salt; 3.0 mg/kg i.p.), did not increase oral activity. The mixed 5 HT1C and 5-HT2 receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a slight increase in oral activity in control rats and a marked increase in oral activity in 6-OHDA-lesioned rats. In the 6-OHDA group the peak effect of 76.5 +/- 4.1 oral movements occurred with an m-CPP 2-HCl dose of 4.0 mg/kg. Pindolol (1.0 mg/kg i.p.), ketanserin tartrate (5 mg/kg i.p.) and MDL-72222 (3-tropanyl-3,5 dichlorobenzoate; 10 mg/kg s.c.), antagonists with high affinity for 5-HT1A,1B, 5 HT2 and 5-HT3 receptors, respectively, did not attenuate m-CPP actions. However, mianserin HCl (1.0 mg/kg s.c.), an antagonist with high affinity for 5-HT1C and 5 HT2 receptors, attenuated the oral response to m-CPP.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602368 TI - Time course of the distribution of morphine in brain regions and spinal cord after intravenous injection to spontaneously hypertensive and normotensive Wistar Kyoto rats. AB - Previous studies from this laboratory have demonstrated that the analgesic and hyperthermic effects of morphine were found to be greater in spontaneously hypertensive (SHR) rats than in normotensive Wistar-Kyoto (WKY) rats. The enhanced response to morphine could not be explained on the basis of any of the pharmacokinetic parameters of morphine in the serum. In order to determine the possible contribution of altered distribution of morphine in the central nervous system in the differences in the pharmacological response to morphine in the two strains, the time course of the distribution of morphine was determined in brain regions and spinal cord after its i.v. administration. SHR and WKY rats were injected with morphine (10 mg/kg). At various times (5, 30, 60, 120 and 360 min) after the injection of morphine, brain regions (hypothalamus, cortex, hippocampus, midbrain, pons and medulla, striatum and amygdala) and spinal cord were collected. The level of morphine in the tissues was determined by using a highly sensitive and specific radioimmunoassay method. Five minutes after morphine injection, the concentration of morphine was the highest in the spinal cord. Among the brain regions, the highest concentration of morphine was in the hypothalamus and the lowest in the amygdala. In all the brain regions and spinal cord, the concentration of morphine was significantly higher in the SHR than in the WKY rats. Similar effects were observed at 30, 60 and 120 min after morphine injection. At 360 min, the hypothalamus, cortex and spinal cord of the SHR rats had higher concentrations of morphine than the WKY rats, but the other regions did not show differences in the morphine levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602369 TI - Homeostasis of sulfate and 3'-phosphoadenosine 5'-phosphosulfate in rats after acetaminophen administration. AB - Acetaminophen (AA) is a drug whose biotransformation by sulfation is easily saturated. We have previously demonstrated in rats that its dose-dependent kinetics appear to be due to depletion of 3'-phosphoadenosine 5'-phosphosulfate (PAPS). In order to determine if the depletion of PAPS might be due to a lack of inorganic sulfate, we characterized the effect of AA not only on the homeostasis of PAPS but also on its precursor, sulfate. The maximum excretion of AA-sulfate was observed after 75 mg/kg of AA, i.p., and higher dosages did not increase its excretion. AA dosages between 150 to 600 mg/kg, i.p., 2 hr after dosing depleted 60 to 80% of hepatic PAPS. Hepatic PAPS levels returned to control values 16 to 20 hr after dosing with 600 mg/kg of AA. AA decreased serum sulfate to a similar degree (80%) and duration (16 hr) as did hepatic PAPS. AA also lowered sulfate concentrations in liver, but to a somewhat lesser extent (65%) than in serum. Hepatic sulfate levels returned to control values at 16 to 24 hr after dosing with AA. Even though AA did not alter renal PAPS concentrations, it did produce a 65% decrease in the renal sulfate levels. In summary, these studies demonstrate that AA markedly depletes PAPS concentrations in liver, but not in kidney, and drastically decreases serum and tissue sulfate concentrations. Our findings indicate that the capacity-limited sulfation of AA is due to the limited availability of hepatic PAPS, which in turn is limited by the availability of sulfate in liver. PMID- 1602370 TI - Impaired biliary excretion of acetaminophen glucuronide in the isolated perfused rat liver after acute phenobarbital treatment and in vivo phenobarbital pretreatment. AB - The influence of phenobarbital (PB) on the hepatobiliary disposition of acetaminophen (APAP), acetaminophen glucuronide (AG) and acetaminophen sulfate (AS) was examined in the recirculating isolated perfused rat liver (IPL). PB was administered as a 5-mumol bolus to the IPL (acute) or in vivo (75 mg/kg/day, i.p., x 5 days), followed by a 48-hr washout, before addition of an APAP (66 mumol) bolus to the IPL. Acute PB administration to the IPL did not affect the total hepatic clearance of APAP or the formation clearance to AG and AS. The rate constant for the biliary excretion of AG and the percentage of the dose recovered in bile as AG were decreased significantly after the acute PB dose. In vivo PB pretreatment induced significantly the UDP-glucuronyltransferases (i.e., an increase in APAP clearance, the formation clearance to AG and in the estimate of the AG formation rate constant). The estimate of the AG sinusoidal egress rate constant after in vivo PB pretreatment also was increased significantly. The AG biliary excretion rate constant and the percentage of the dose recovered in bile as AG were decreased approximately 5-fold after in vivo PB pretreatment, similar to values obtained after acute PB administration. PB was detected only after acute PB administration, whereas unconjugated p-hydroxyphenobarbital was not detected after either treatment. These data indicate that neither PB itself nor an induction effect related to in vivo PB pretreatment are required directly to impair hepatobiliary disposition. PMID- 1602371 TI - In vitro pharmacology of a nonpeptidic angiotensin II receptor antagonist, SC 51316. AB - The properties of a novel nonpeptidic angiotensin II (AII) receptor antagonist, 2,5-dibutyl-2,4-dihydro-4-([2-(1H-tetrazol-5-yl)(1,1'-biphenyl) -4'-yl]methyl)-3H 1,2,4-triazol-3-one (SC-51316), are described. SC-51316 inhibited [125I]AII binding selectively to the AT1 receptor with IC50 values of 3.6 and 5.1 nM in rat adrenal cortical and rat uterine membrane preparations, respectively. The compound was a competitive and reversible antagonist of AII-mediated contraction of rabbit aortic rings with a pA2 of 8.86. In addition, SC-51316 inhibited AII induced aldosterone release from rat adrenal zona glomerulosa cells and blocked inhibition of renin release by AII from rat kidney slices with pA2 values of 8.62 and 8.9, respectively. The agent (0.1 mM) did not inhibit angiotensin-converting enzyme or plasma renin activity. These data demonstrate that SC-51316 is a potent AII receptor antagonist which may prove to be useful as a pharmacologic tool for studying the role of the renin-angiotensin system in cardiovascular diseases. PMID- 1602372 TI - Evidence for two cholecystokinin receptors mediating the contraction of the guinea pig isolated ileum longitudinal muscle myenteric plexus. AB - In guinea pig isolated ileum longitudinal muscle myenteric plexus, cholecystokinin octapeptide (CCK-8S) produced a rapid (phasic) contraction followed by a slower tonic phase. The tetrapeptide derivative CCK-4 and pentagastrin elicited only the phasic response up to 10(-6) M, whereas the tonic phase was also apparent at higher concentrations. The rank order of potency for the effect of agonists on the tonic and phasic responses were CCK-8S much greater than gastrin greater than CCK-8US congruent to pentagastrin greater than CCK-4 and CCK-8S greater than gastrin congruent to pentagastrin greater than CCK-4 greater than CCK-8US, respectively. Phasic responses of CCK-8S and CCK-4 were sensitive to atropine, whereas the tonic response could be completely abolished with the neurokinin-1 antagonist GR82334. The CCK-A receptor antagonist L-364,718 up to 10(-7) M had little effect on the phasic contracture of CCK-4. The CCK B/gastrin receptor antagonist L-365,260 had no effect on the CCK-8S phasic response up to 10(-7) M, but antagonized the phasic response induced by low concentrations of CCK-4 in a competitive manner with an estimated pKB of 8.51. This value is close to that of 8.53 found in a guinea pig cortical binding assay. Both the second phase of the CCK-4 phasic concentration response curve (CRC) and the tonic contraction were insensitive to L-365,260.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602373 TI - Platelet-activating factor reduces spinal cord blood flow and causes behavioral deficits after intrathecal administration in rats through a specific receptor mechanism. AB - Platelet-activating factor (PAF) is a phospholipid that has been implicated in the pathophysiology of delayed tissue damage after various forms of brain injury including ischemia, hypoxia and trauma. To examine its effects in the spinal cord, PAF was administered intrathecally to rats. PAF caused dose-dependent (30 100 nmol) decreases in spinal cord blood flow, in motor function or in survival. These actions were not reproduced by the biologically inactive precursor lyso-PAF or the enantiomer of this alkyl-phospholipid, which is not active at PAF receptors. PAF-induced changes were blocked completely by the selective receptor antagonist WEB 2170. Together, these findings demonstrate that PAF can alter spinal cord blood flow and motor function through a specific receptor mechanism, suggesting that this phospholipid may play a role in secondary tissue damage after spinal cord injury. PMID- 1602374 TI - Nonionic diffusion of salicylic acid through MDCK cell monolayers. AB - MDCK-I cells, grown on collagen-coated filters, were used as a model of the distal nephron to study the nonionic diffusion of salicylic acid. The apparent transcellular permeability (PSal, centimeters per second) and intracellular content (ContSal, picomoles) of [14C]salicylic acid (ionized and nonionized) were measured from both apical-to-basolateral and basolateral-to-apical unidirectional fluxes. During the measurement of apical-to-basolateral fluxes at 21 degrees C, both PSal and ContSal correlated directly with the proportion of nonionized salicylic acid in the apical medium over the pH range 6.0-7.4. This indicated that the observed permeability was due to pure nonionic diffusion. However, in the basolateral-to-apical direction, the correlation was less evident and ContSal was 10 to 20 times higher, although PSal was of the same magnitude. These observations could not be explained by facilitated transport of anionic salicylic acid, at 21 degrees C, because 1 mM probenecid, 1 mM p-aminohippurate and 1 mM cold salicylic acid did not abolish the higher intracellular content obtained during basolateral-to-apical fluxes. Raising the temperature produced only a gradual increase of PSal measured in the basolateral-to-apical direction and an unexpected decrease of ContSal. Because basolateral-to-apical facilitated transport does not play a significant role, the most plausible reason for the higher ContSal during basolateral-to-apical fluxes is that the apical membrane possesses a much lower (10- to 20-fold less) salicylic acid permeability than the basolateral membrane and constitutes the rate-limiting step for transcellular salicylic acid flux. PMID- 1602375 TI - Beneficial effect of MCI-154, a cardiotonic agent, on ischemic contractile failure and myocardial acidosis of dog hearts: comparison with dobutamine, milrinone and pimobendan. AB - The effects of MCI-154, a cardiotonic agent with Ca++ sensitizing actions, on the ischemic contractile failure and myocardial acidosis were studied in the dog heart, in which the left anterior descending coronary artery (LAD) was partially occluded for 90 min, and compared with those of dobutamine, milrinone, pimobendan and isosorbide dinitrate (ISDN). Partial occlusion of LAD decreased segment shortening (measured by sonomicrometry) and myocardial pH (assessed by a micro glass pH electrode) in the ischemic myocardium. MCI-154, when administered i.v. 30 min after ischemia, improved the segment shortening in the ischemic zone, whereas dobutamine, milrinone and pimobendan failed to improve it when the drugs increased peak positive left ventricular dP/dt. Among the cardiotonic agents tested only MCI-154 attenuated myocardial acidosis during ischemia. The degree of the attenuation of acidosis by MCI-154 was equivalent with that by ISDN. However, the improvement of the ischemic zone segment shortening by MCI-154 was more pronounced than that by ISDN. These results suggest that in addition to the attenuation of myocardial acidosis the positive inotropic action of MCI-154, presumably increasing the responses of myofilaments to Ca++, may be possibly responsible for the improvement of regional contractile function in the ischemic myocardium. Thus, MCI-154 may be useful in the management of ischemic heart failure. PMID- 1602376 TI - Homocysteine remethylation during nitrous oxide exposure of cells cultured in media containing various concentrations of folates. AB - Nitrous oxide irreversibly inactivates cob(I)alamin, which serves as a cofactor of the enzyme methionine synthase catalyzing the remethylation of homocysteine to methionine. In patients exposed to nitrous oxide, increase in plasma homocysteine is a responsive indicator of cob(I)alamin inactivation. In the present work, we measured the inactivation of methionine synthase and the concurrent homocysteine export rate of two murine and four human cell lines during nitrous oxide exposure. When cultured in a standard medium with high content (2.3 microM) of folic acid, the methionine synthase of all cell types was inactivated at an initial rate of 0.05 to 0.14 h-1. The inactivation curves leveled off, and a residual activity of 15 to 45% was observed after 48 h of nitrous oxide exposure. The rate and extent of the nitrous oxide-induced inactivation were markedly reduced when the cells were transferred and cultured (greater than 10 days) in a medium containing low concentration (10 nM) of 5-methyltetrahydrofolate. The methionine synthase inactivation increased in a dose-dependent manner when the 5 methyltetrahydrofolate content of the medium was increased from 3 nM to 2.3 microM. The inactivation of methionine synthase was associated with a marked enhancement of homocysteine export rate of murine fibroblasts and a moderate increase in export from two human glioma cell lines. In contrast, in three leukemic cell lines (murine T-lymphoma R 1.1 cells, human promyelocytic leukemia HL-60 cells and human acute myelogenous leukemia KG-1a cells), the homocysteine export rates were not increased during nitrous oxide exposure. In the responsive murine fibroblasts and the glioma cells, the homocysteine export rate varied inversely to the changes in methionine synthase activity induced by nitrous oxide exposure at different concentrations of folate in the medium. The enhancement of homocysteine export rate of some cell types during nitrous oxide exposure probably reflects inhibition of homocysteine remethylation in intact cells, and highlights the utility of extracellular homocysteine as an indicator of metabolic flux through the methionine synthase pathway. No enhancement of homocysteine export despite inactivation of methionine synthase in three leukemic cell lines questions the functional state of the enzyme in these cells. PMID- 1602378 TI - Pharmacologic characterization of the muscularis mucosae in three regions of the rabbit colon. AB - The aim of the present in vitro study was to provide information on the pharmacologic properties of the muscularis mucosae in three regions of the rabbit colon. Proximal muscularis mucosae exhibited spontaneous contractions whose frequency was independent of endogenous acetylcholine. In the mid and distal colon, spontaneous contractile frequencies were depressed by atropine and enhanced by eserine. Muscularis mucosae from all regions responded to acetylcholine, ADP, AMP, ATP, bradykinin, histamine, methoxamine, substance P, vasoactive intestinal polypeptide but not cholecystokinin octapeptide or gamma aminobutyric acid. Low concentrations of norepinephrine caused propranolol sensitive relaxations of proximal colonic muscularis mucosae whereas high concentrations evoked phentolamine-sensitive contractions. In the mid and distal colon, norepinephrine caused relaxations which were poorly antagonized by propranolol. Proximal colonic muscularis mucosae responded to electrical stimulation with an atropine- and tetrodotoxin-sensitive "on contraction." Responses from the mid and distal colon were tetrodotoxin-sensitive and consisted of an atropine-sensitive "duration contraction" followed by a propranolol insensitive "off relaxation" which was not mediated by prostaglandin synthesis, a purine, or vasoactive intestinal polypeptide. These data suggest that the rabbit colonic muscularis mucosae possesses alpha-1 adrenoceptors, histamine H1, muscarinic, P2 purinoceptors and beta adrenoceptors. However, their relative importance and the nature of the intrinsic innervation suggests considerable specialization of this muscle layer in different regions of the rabbit colon. PMID- 1602377 TI - N-methyl-D-aspartate increases acetylcholine release from rat striatum and cortex: its effect is augmented by choline. AB - We examined the effects of N-methyl-D-aspartate (NMDA), a glutamate agonist, and of glutamate itself, on acetylcholine (ACh) release from superfused rat striatal slices. In a Mg(++)-free medium, NMDA (32-1000 microM) as well as glutamate (1 mM) increased basal ACh release by 35 to 100% (all indicated differences, P less than .05), without altering tissue ACh or choline contents. This augmentation was blocked by Mg++ (1.2 mM) or by MK-801 (10 microM). Electrical stimulation (15 Hz, 75 mA) increased ACh release 9-fold (from 400 to 3660 pmol/mg of protein): this was enhanced (to 4850 pmol/mg of protein) by NMDA (100 microM). ACh levels in stimulated slices fell by 50 or 65% depending on the absence or presence of NMDA. The addition of choline (40 microM) increased ACh release both basally (570 pmol/mg of protein) and with electrical stimulation (6900 pmol/mg of protein). In stimulated slices choline acted synergistically with NMDA, raising ACh release to 10,520 pmol/mg of protein. The presence of choline also blocked the fall in tissue ACh. No treatment affected tissue phospholipid or protein levels. NMDA (32 320 microM) also augmented basal ACh release from cortical but not hippocampal slices. Choline efflux from striatal and cortical (but not hippocampal) slices decreased by 34 to 50% in Mg(++)-free medium. These data indicate that NMDA-like drugs may be useful, particularly in combination with choline, to enhance striatal and cortical cholinergic activity. ACh release from rat hippocampus apparently is not affected by NMDA receptors. PMID- 1602379 TI - Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. AB - Isomers (alpha- and beta-) of boswellic acids (BAs), 11-keto-beta-BA and their acetyl derivatives were isolated from the gum resin of Boswellia serrata. BA and derivatives concentration dependently decreased the formation of leukotriene B4 from endogenous arachidonic acid in rat peritoneal neutrophils. Among the BAs, acetyl-11-keto-beta-BA induced the most pronounced inhibition of 5-lipoxygenase (5-LO) product formation with an IC50 of 1.5 microM. In contrast to the redox type 5-LO inhibitor nordihydroguaiaretic acid, BA in concentrations up to 400 microM did not impair the cyclooxygenase and 12-lipoxygenase in isolated human platelets and the peroxidation of arachidonic acid by Fe-ascorbate. The data strongly suggest that BAs are specific, nonreducing-type inhibitors of the 5-LO product formation either interacting directly with the 5-LO or blocking its translocation. PMID- 1602380 TI - Effects of d-myo-inositol-1,2,6-trisphosphate on neuropeptide Y-induced potentiation of various vasoconstrictor agents in the rat. AB - The adrenergic cotransmitter neuropeptide Y (NPY) induces vascular smooth muscle contraction by occupying postsynaptic Y1 receptors and by enhancing the vasoconstriction induced by a series of other pressor agents. In particular, NPY modulates the blood pressure response to alpha-1 adrenergic agonists and angiotensin II. The inositol phosphate derivative, d-myo-inositol-1,2,6 trisphosphate (PP56), is a novel NPY antagonist which within a defined dose range selectively blocks the effects of exogenously administered NPY in vivo. In the pithed animal as well as in the freely moving Sprague-Dawley rat, an i.v. bolus administration of PP56 (2 mg/kg) followed by an infusion (20 mg/kg/hr for 30 min) inhibited the approximate 50% increase in mean arterial blood pressure induced by a continuous infusion of NPY (2 micrograms/kg/min for 10 min). Furthermore, PP56 treatment completely inhibited the enhancement induced by NPY (0.1 microgram/min for 50 min or 2 micrograms/kg/min for 10 min) of the pressor responses to preganglionic sympathetic nerve stimulation (in the pithed rat) and to i.v. bolus injections of noradrenaline (20 ng), the indirect sympathomimetic tyramine (40 micrograms) as well as to angiotensin II (10 ng). These results show that PP56, representing a new class of synthetic nonpeptide drugs, is capable of antagonizing the vascular smooth muscle contractile as well as the potentiating effects of NPY in vivo in the pithed as well as the conscious rat. PMID- 1602381 TI - Electromechanical effects of the putative potassium channel activator celikalim (WAY-120,491) on feline atrial and ventricular muscle. AB - Celikalim (WAY-120,491) is a putative potassium channel activator that has been shown to lower blood pressure in animal models and humans. In the present study, we have examined the effects of celikalim on contractility and ionic currents in feline cardiac muscle. Celikalim was found to decrease contractility in electrically stimulated (2 Hz frequency) left atrial and right ventricular papillary muscle preparations with IC50 values of 0.95 +/- 0.12 microM (n = 6) and 0.29 +/- 0.07 microM (n = 5), respectively. Glyburide (1 microM) reversed the celikalim-induced negative inotropy (left atrial halves). Celikalim was also shown to activate a glyburide-sensitive current in voltage-clamped isolated ventricular myocytes that reversed close to the calculated value of the potassium equilibrium potential (n = 4 cells). In addition, celikalim was found to inhibit voltage-activated calcium current (L-type) in isolated ventricular myocytes (51 +/- 2% inhibition at 1 microM; n = 4 cells). We conclude that celikalim is a potassium channel activator and hypothesize that both the negative inotropy and the glyburide-sensitive current evoked by this drug are mediated by ATP-regulated potassium channels. Inhibition of voltage-activated calcium channels by celikalim may also contribute to the negative inotropy induced by this drug. PMID- 1602382 TI - Transport of recombinant CD4 through the rat blood-brain barrier in vivo. AB - One class of potential acquired immunodeficiency syndrome therapeutics are derivatives of recombinant CD4 (rCD4). Therefore, the present investigations use in vivo techniques to measure the rate at which [3H]rCD4 is transported through the blood-brain barrier (BBB). In addition, the binding of labeled rCD4 to isolated human and bovine brain capillaries is measured. These studies show that [3H]CD4 is removed rapidly from the bloodstream with a half-time of 12.6 +/- 0.9 min. The volume of distribution (Vd) of the protein in brain increases with time and reaches a Vd that is 11.1 +/- 1.1-fold greater than the brain Vd of plasma marker, native rat serum albumin. In addition, [3H]rCD4 is extracted rapidly by the kidney and the ratio of rCD4 Vd to native rat serum albumin Vd in the rat kidney reaches 99 +/- 5 at 60 min after i.v. injection. rCD4 is shown to undergo transcytosis through the BBB using an internal carotid artery perfusion/capillary depletion method coupled with gel filtration fast protein liquid chromatography. In conclusion, these studies report the unexpected finding that rCD4 is transportable through the BBB. rCD4 is a cationic protein and the mechanism of rCD4 transport through the BBB may be analogous to the absorptive-mediated transcytosis of other polycationic proteins. PMID- 1602383 TI - Age and gender influence the stereoselective pharmacokinetics of propranolol. AB - The effect of age and gender on the stereoselective pharmacokinetics of propranolol was studied in 12 young (25 to 33 years old) and 12 elderly (62 to 79 years old) healthy nonsmoking volunteers, half of whom were female. Racemic propranolol was administered (80 mg p.o.) each 8 hr for seven doses. Serum was obtained just before (0 time) and at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after the final dose and analyzed for propranolol enantiomers. The serum concentration of alpha-1 acid glycoprotein was determined before propranolol administration. The binding of each enantiomer to serum proteins was determined in samples obtained before propranolol administration and two hr after the final dose of propranolol. We found that the intrinsic hepatic clearance of S-propranolol was about 30% smaller in the elderly than in the young, whether it was calculated for total or unbound drug. Additionally, the elimination half-lives of both enantiomers were 2- to 3-fold prolonged in the elderly compared with the young. In all subjects regardless of age or sex the intrinsic hepatic clearance of the total (bound plus free) S-isomer was smaller than that of the R-isomer. There was no age-related difference in alpha-1 acid glycoprotein concentration or protein binding of either enantiomer of propranolol. However, there was a gender-related difference with the females having significantly greater binding of the S enantiomer than the males.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602384 TI - Inhibition of dihydropyridine metabolism in rat and human liver microsomes by flavonoids found in grapefruit juice. AB - The effects of naringenin, quercetin and kaempferol, flavonoids found in grapefruit as glycosides, on the metabolism of nifedipine and the enantiomers of felodipine were studied in microsomes from rat and human liver. Flavonoid concentrations of 10, 50 and 100 mumol/l were added to rat liver microsomes. The metabolism of nifedipine, (R)- and (S)-felodipine was inhibited to a similar extent, and the inhibition was dependent on the chemical structure and the concentration of flavonoid. Naringenin had lower inhibitory potency than quercetin and kaempferol. These flavonoids exhibited the same order of inhibitory potency in human liver microsomes. No inhibition of naringenin was found, however, until higher concentrations, 300 and 500 mumol/l, were added. A likely mechanism is inhibition of cytochrome P-450 IIIA4, the isoenzyme that catalyzes the oxidation of the dihydropyridine ring to form the corresponding pharmacologically inactive pyridine metabolite. This is a predominant metabolic step that determines the extent of first-pass extraction of dihydropyridines. Grapefruit juice has been shown recently to increase the p.o. bioavailability of the dihydropyridine calcium antagonists nifedipine and felodipine. The interaction may be explained by an inhibition of the first-pass metabolism by flavonoids in grapefruit juice. Furthermore, the results indicate that the rat may be used for in vivo studies of interactions between flavonoids and dihydropyridines or other drugs that are metabolized by cytochrome P-450 IIIA4. PMID- 1602385 TI - Surface binding and intracellular uptake of gentamicin in the cultured kidney epithelial cell line (LLC-PK1). AB - Aminoglycoside antibiotics such as gentamicin are taken up by renal proximal tubular cells, yet little is known regarding the biochemical characteristics of the transport process at the cellular level. In this report, cellular handling of gentamicin was studied in the cultured kidney epithelial cell line LLC-PK1. After 2 days of incubation of the cells with gentamicin, cell-associated gentamicin decreased rapidly during the first 30 min when the cells were incubated in gentamicin-free medium, then decreased slowly. The apparent half-life of the latter phase, which should represent release from the intracellular compartment, was about 2.0 days. The rapid release of gentamicin should consist of two components, one is a release from the cell surface membrane and the other from domes. Cell surface binding of gentamicin was dependent on the ambient ionic strength. The intracellular uptake was inhibited by low temperature, neomycin, metabolic inhibitors and reagents which interact with the cytoskeleton. On the other hand, the uptake was not affected by d-glucose, organic cations and an organic anion. Thus, by estimating the intracellular gentamicin separately from the drug localized in other compartments, it is concluded that gentamicin is taken up by LLC-PK1 cells via an adsorptive endocytosis. The endocytosis of gentamicin should be dependent on metabolic energy and cytoskeletal function. PMID- 1602386 TI - Reduction of aspirin-induced gastric damage in rats by interleukin-1 beta: possible involvement of endogenous corticosteroids. AB - Administration of interleukin-1 (IL-1; 0.01-3 microgram/kg) by either i.p. or intragastric routes to rats reduced aspirin-induced gastric damage. These effects of IL-1 were not subject to desensitization by its pretreatment and were obtained without modification of the acute anti-inflammatory efficacy of aspirin. Gastroprotection could be effected without major modification of gastric tissue to form prostaglandins I2 or E2. A dose-related decrease of the acidic gastric fluid secretion induced by aspirin was observed with i.p. administered IL-1 was found to reduce gastric fluid volume only at the highest dose tested, although this was not associated with increased gastroprotection. By using adrenalectomized rats the gastric damage induced by aspirin was increased approximately 3-fold. IL-1 treatment, albeit with higher dosage, again reduced lesion formation. Treatment of adrenalectomized rats with dexamethasone and IL-1 synergistically reduced the gastric damage caused by aspirin. In normal rats these treatments caused only an additive reduction of lesion formation although the presence of endogenous glucocorticoid in these animals may mask any effects of the exogenously administered dexamethasone. The glucocorticoid-receptor antagonist, RU 38486, also potentiated aspirin-induced gastric damage and reduced the gastroprotective efficacy of IL-1 without modifying its effect on gastric fluid volume. The data indicate that gastroprotective actions of IL-1 are unlikely to be related upon effects on prostaglandin synthesis or gastric secretion. Endogenous glucocorticoids appear to have a modulatory role in controlling the severity of gastric damage evoked by aspirin and may potentiate the protective actions of IL-1. PMID- 1602387 TI - Nephrotoxicity of the glutathione and cysteine conjugates of 2-bromo-2-chloro-1,1 difluoroethene. AB - The mercapturate S-(2-bromo-2-chloro-1,1-difluoroethyl)-N-acetyl-L-cysteine, which is apparently derived from the halothane degradation product 2-bromo-2 chloro-1,1-difluoroethene, is excreted in urine. S-(2-Bromo-2-chloro-1,1 difluoroethyl)glutathione (BCDFG) and S-(2-bromo-2-chloro-1,1-difluoroethyl)-L cysteine (BCDFC) are putative intermediates in the metabolism of 2-bromo-2-chloro 1,1-difluoroethene and are analogs of nephrotoxic and cytotoxic S-haloalkyl glutathione and cysteine conjugates. The objective of the research was to study the nephrotoxicity and cytotoxicity of 2-bromo-2-chloro-1,1-difluoroethene derived S-conjugates. BCDFG and BCDFC were nephrotoxic in Fischer 344 rats and caused diuresis, increases in urine glucose and protein concentrations, in blood urea nitrogen concentrations, in kidney/body weight percentages and in serum glutamate-pyruvate transaminase activities. Both S-conjugates also produced severe morphological changes in the kidneys, especially in the proximal tubules. Morphological changes indicative of hepatotoxicity were seen in some animals given BCDFG and BCDFC. Both BCDFG and BCDFC were cytotoxic to LLC-PK1 cells, as shown by lactate dehydrogenase release into the medium. The cytotoxicity of BCDFG was blocked by the gamma-glutamyltransferase inhibitor acivicin, and the cytotoxicity of both BCDFG and BCDFC was blocked by the cysteine conjugate beta lyase inhibitor aminooxyacetic acid. Also, S-(2-bromo-2-chloro-1,1-difluoroethyl) DL-alpha-methylcysteine, which can not be metabolized by beta-lyase, was not toxic to LLC-PK1 cells. These in vivo and in vitro data provide evidence that BCDFG and BCDFC are nephrotoxic and that their toxicity is dependent on renal bioactivation by cysteine conjugate beta-lyase. PMID- 1602388 TI - Self-administration of cocaine by humans: choice between smoked and intravenous cocaine. AB - Ten healthy adult male research volunteers reporting smoked and i.v. cocaine use resided on a Clinical Research Center for 2 weeks and participated in nine daily sessions. A session consisted of seven choice trials. The first two trials were sampling trials in which subjects received one dose each of i.v. cocaine hydrochloride (0, 16 and 32 mg) and smoked cocaine base (0, 25 and 50 mg). Each of the remaining five trials was a choice trial in which subjects could choose to self-administer either of the doses from the initial two trials. Subjects 1) reliably chose active doses of cocaine compared to placebo, 2) chose to self administer the low-smoked cocaine dose about as often as either the low or high i.v. cocaine doses and 3) reliably chose the high-smoked cocaine dose when compared to either active i.v. dose. With few exceptions, both low doses and high doses produced similar subjective and cardiovascular effects after the initial dose, regardless of the route of administration. This suggests that initial effects were not predictive of subsequent choice. Cumulative doses of smoked cocaine increased scores on a number of subjective-effects measures that were not similarly increased by cumulative doses of i.v. cocaine. These differences were predictive of smoked cocaine self-administration. After session ratings of drug "Liking" and "Quality" differentiated smoked from i.v. cocaine, reflecting route choice. However, there were no significant differences between these ratings for low and high doses. These results provide information about the relationship between subjective drug effects and drug self-administration, and demonstrate the utility of a choice procedure in analyzing these relationships. PMID- 1602389 TI - Comparison of the serotonin receptors that mediate smooth muscle contraction in canine and porcine coronary artery. AB - Serotonin (5-HT) is one important mediator of the coronary vasospasm and occlusion associated with thrombosis and atherosclerosis. 5-HT concentration dependently contracted both canine and porcine coronary artery rings in vitro. In the dog, 5-HT-induced contraction was not blocked by either LY53857 (1 microM) or ketanserin (1 microM), but was blocked by the nonselective 5-HT receptor antagonist 1-naphthylpiperazine (1-NP) (100 nM), indicating 5-HT receptor involvement. Unlike the dog, both LY53857 (1 microM) and ketanserin (30 nM) antagonized 5-HT-induced contraction in pig arteries. Dissociation constants for LY53857 and ketanserin in porcine arteries were compared with those in rat jugular vein, a tissue possessing a well characterized 5-HT2 receptor. Both LY53857 (3 nM) and ketanserin (3 nM) antagonized 5-HT-induced contraction in rat jugular vein; however, the affinities of LY53857 and ketanserin in the rat jugular vein were significantly higher than those in the pig coronary. The rank order contractile potency for 5-HT, (alpha Me-5-HT) and sumatriptan in porcine coronary artery was consistent with that established for a 5-HT2 receptor, whereas the rank order potency in canine coronary artery indicated non-5-HT2 receptor involvement. Sumatriptan, a 5-HT1D receptor-selective agonist, was equieffective to 5-HT in contracting the canine coronary artery, a response inhibited by 1-NP (100 nM). Sumatriptan failed to contract either the pig coronary or rat jugular vein. In summary, significant differences exist in the 5 HT receptors that mediate contraction between the canine and porcine coronary artery.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602390 TI - Sex-, age- and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver in relation to the regulation of cytochrome P450IIE1 and P450IIC11 content. AB - Sex-, age- and pregnancy-induced changes in the metabolism of toluene and trichloroethylene in rat liver were investigated in relation to the regulation of cytochrome P450IIE1 and P450IIC11 content using monoclonal antibodies. Immature male rats had a higher level of microsomal protein than females, and this increased with development; however, no difference by sex was found at puberty. No difference in cytochrome P450 content was seen between immature male and female rats; the content increased with development only in males, so that a sex difference in cytochrome P450 content occurred at puberty. Pregnancy decreased the cytochrome P450 content but not that of the microsomal protein. The rate of formation of benzyl alcohol from toluene was 4 times higher in mature than in immature male rats at a high concentration of toluene, but no difference was seen at a low toluene concentration. In contrast, the rate was lower in mature female rats than in immature ones at a low toluene level and no difference was seen at the high concentration. A sex difference was thus found in benzyl alcohol formation at puberty at both concentrations of toluene. The levels of o- and p cresol formation in liver were similar in males and females but the rate decreased during development of females. The rate of metabolism of trichloroethylene was higher in immature than in mature male and female rats, especially at a low substrate level, and no sex difference in metabolism was seen with either age or concentration of trichloroethylene. Pregnancy decreased the metabolism of both toluene and trichloroethylene.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602391 TI - Effect of N-substituted arginine compounds on blood pressure in anesthetized rats. AB - Inhibition of endothelium-dependent relaxation by NG-monomethyl L-arginine (L NMMA) and its reversal by excess L- but not D-arginine is used to support the hypothesis that the endothelium-derived relaxing factor (EDRF) is generated exclusively from the metabolism of L-arginine. However, in freshly isolated vascular tissues, L-arginine is a poor vasodilator when compared to the N substituted arginine compound, N alpha-benzoyl L-arginine ethyl ester (BAEE). Here, we show that such N-substituted compounds are potent hypotensive agents in anesthetized rats. In contrast, L-arginine elicits hypotensive effect only at higher concentrations (greater than 100 mg/kg). This effect of L-arginine is not antagonized by L-NMMA. Furthermore, D-arginine, L-homoarginine and L-lysine also have hypotensive effects at these concentrations. Indomethacin treatment partially attenuates the hypotensive effects of the basic amino acids. In contrast, the hypotensive effect of BAEE is antagonized by L-NMMA in a dose dependent manner and by methylene blue, which is an inhibitor of soluble guanylate cyclase. In addition, substitution at the arginine moiety determines the hypotensive effect. When the amino acid glycine is inserted between the benzoyl group and arginine as in benzoyl-glycine-arginine, significant attenuation of the hypotensive effect is observed. These data demonstrate that compounds such as BAEE generate an EDRF-like agent in vivo and basic amino acids such as L-arginine elicit hypotension at concentrations above 100 mg/kg by mechanisms other than the generation of EDRF. PMID- 1602392 TI - Calcium antagonists block angiotensin II-mediated vasoconstriction in humans: comparison with their effect on phenylephrine-induced vasoconstriction. AB - Calcium antagonists are known to decrease peripheral vascular resistance in vivo in humans. The mechanism of this vascular relaxation has not been clearly elucidated. Vascular tone is maintained by several endogenous neurohumoral systems including sympathetic nervous system activity and angiotensin II. We compared and contrasted the capacity of calcium antagonist drugs to prevent angiotensin II and phenylephrine-induced alpha-1 adrenergic vasoconstriction using brachial artery infusion and measurement of forearm blood flow by strain gauge plethysmography. In a dose-dependent manner, calcium antagonists blocked angiotensin II-induced vasoconstriction. The rank order of this blockade was nifedipine greater than verapamil greater than diltiazem. Nifedipine and verapamil, but not diltiazem blocked alpha-1 adrenergic (phenylephrine-induced) vasoconstriction. At 7.64 and 19.1 micrograms/min infusion rates for nifedipine and verapamil, respectively, they abolished the angiotensin II effect; however, the phenylephrine effect was incompletely blocked. Calcium antagonist-induced vascular relaxation in vivo in humans is in part explained by their capacity to block angiotensin II-mediated vasoconstriction. In addition, two calcium antagonists (nifedipine and verapamil) may inhibit alpha-1 adrenergic vasoconstriction. PMID- 1602393 TI - Caffeine drug discrimination in humans: acquisition, specificity and correlation with self-reports. AB - This study evaluated the discriminative stimulus effects of caffeine in humans. Nine normal male and female volunteers (ages 18-28) were trained to discriminate between the methylxanthine central nervous system stimulant caffeine (320 mg/70 kg, p.o.) and placebo. Monetary reinforcers were earned for identifying correctly the letter code associated with each substance. After four training sessions, the ability to discriminate between the two training conditions was tested for 20 sessions (test-of-acquisition). In subjects who met the criterion for discrimination (i.e., greater than or equal to 85% correct responding on greater than or equal to 4 consecutive sessions during the last 10 test-of-acquisition sessions) dose-effect curves for caffeine (0, 56, 100, 180, 240 and 320 mg/70 kg) and for the benzodiazepine triazolam (0, 0.10, 0.32 and 0.56 mg/70 kg) were determined. Seven of the nine subjects learned the caffeine-placebo discrimination and their performance improved across the 20 test-of-acquisition sessions. The training dose of caffeine (320 mg/70 kg) produced stimulant-like self-reports that differed from placebo when the letter codes were identified correctly, but not when the letter codes were identified incorrectly. Novel caffeine doses produced dose-related increases in caffeine-appropriate responding (N = 4), whereas triazolam produced predominantly placebo-appropriate responding (N = 3) and self-reports that differed from both caffeine and placebo. Throughout dose-effect curve determinations, the training dose of caffeine and placebo continued to be identified correctly (range: 84-100% correct responding). These results suggest that a caffeine (320 mg/70 kg)-placebo discrimination 1) can be acquired and maintained, 2) is related to self-reported drug effects if the training conditions are correctly identified and 3) has some pharmacological specificity. PMID- 1602394 TI - Comparative antithrombotic effects of heparin, recombinant hirudin and argatroban in a hamster femoral vein platelet-rich mural thrombosis model. AB - The antithrombotic properties of bolus i.v. injections of heparin, of recombinant hirudin (r-hirudin) or of the synthetic competitive thrombin inhibitor Argatroban were investigated in a quantitative hamster femoral vein platelet-rich mural thrombosis model. Heparin at a dose of 100 U/kg prolonged the activated partial thromboplastin time from 26 +/- 15 to 177 +/- 45 sec (P = .001), but did not significantly inhibit platelet-rich thrombus formation (7 +/- 44% inhibition, P = NS vs. placebo). However, 400 U/kg of heparin produced total inhibition of thrombus formation (101 +/- 14+, P less than .06 vs. control). R-hirudin and argatroban inhibited thrombus formation in a dose-dependent manner: 50% inhibition was obtained with 1.4 mg/kg for r-hirudin and with 2.0 mg/kg for Argatroban. A linear correlation was observed between the percentage of inhibition of thrombus formation vs. Activated partial thromboplastin time (r = 0.57, P = .003 for r-hirudin and r = 0.66, P = .002 for Argatroban). These results suggest that thrombin plays a pivotal role in platelet-rich mural thrombus formation, that this small animal model may be useful for investigation of the pharmacodynamics of synthetic thrombin inhibitors and that platelet-rich thrombus formation is inhibited effectively by heparin, r-hirudin and Argatroban. However, r-hirudin and Argatroban cause less profound changes in the coagulant function at doses that inhibit platelet-rich thrombus formation than heparin. PMID- 1602395 TI - Plasma dopa responses during stress: dependence on sympathoneural activity and tyrosine hydroxylation. AB - Dihydroxyphenylalanine (dopa), the precursor of all the endogenous catecholamines, circulates in plasma at a concentration higher than that of the sympathetic neurotransmitter, norepinephrine (NE). Sources of dopa in plasma and the meaning of plasma dopa levels in terms of sympathoneural function have been unclear. Plasma concentrations of dopa, the catecholamines NE, epinephrine and dopamine, the deaminated catechol metabolites dihydroxyphenylglycol and dihydroxyphenylacetic acid, and the O-methylated metabolites methoxyhydroxyphenylglycol and homovanillic acid were measured during immobilization stress in conscious rats. Animals were pretreated with chlorisondamine to block ganglionic neurotransmission or with alpha-methyl-para tyrosine to inhibit tyrosine hydroxylation. Immobilization produced rapid, sustained increases in plasma levels of dopa, catecholamines and catecholamine metabolites. Chlorisondamine decreased base-line plasma dopa and NE levels and abolished the increases in plasma dopa and NE levels during immobilization. alpha Methyl-para-tyrosine administration produced sustained decreases in plasma dopa levels and markedly attenuated immobilization-induced increases in plasma dopa levels. Bilateral adrenalectomy augmented base-line plasma levels of dopa and NE and augmented dopa and NE responses during immobilization. The results indicate that during immobilization stress, increased postganglionic sympathoneural outflow stimulates the synthesis of dopa in sympathetic neurones and enhances release of dopa into the circulation. The data generally support the view that changes in plasma dopa levels during stress reflect in vivo changes in the rate of catecholamine biosynthesis in sympathetic nerve terminals. PMID- 1602396 TI - Pharmacokinetics of cimetidine during lactation: species differences in cimetidine transport into rat and rabbit milk. AB - The disposition of cimetidine, including transfer into milk, was characterized in the rabbits and rats. Nursing rabbits and suckling offspring exhibited similar pharmacokinetics with a mean systemic disease (CL) in the adults and pups of 22.0 +/- 5.2 and 30.4 +/- 8.9 ml/min/kg, respectively. Cimetidine exhibited a distributional time lag and a prolonged T 1/2 in milk compared to serum (70 +/- 15 vs. 33 +/- 5 min), resulting in a time-dependent milk to serum (M/S) drug concentration ratio. The ratio of the area under the time curve of cimetidine in serum and milk was 1.49 +/- 0.37 and was comparable to a diffusional model predicted M/S ratio of 1.16 +/- 0.11. Unbound CL after a high cimetidine infusion regimen (16.6 +/- 7.3 ml/min/kg) was significantly less than that after two lower infusion rates (26.2 +/- 4.9 and 29.4 +/- 12.3 ml/min/kg, respectively). M/S determined at increasing steady-state serum concentrations were 1.03, 1.08 and 1.08, respectively, which agreed well with the corresponding predicted M/S (1.06, 1.14 and 1.13, respectively). Cimetidine was also administered to lactating rats and resulted in a concentration-dependent decrease in CL (11.2 +/- 1.5, 10.8 +/- 2.7 and 7.30 +/- 1.0 ml/min, respectively) after three increasing infusion rates. The steady-state M/S ratio decreased slightly from 31.9 +/- 9.0 to 26.5 +/- 9.5 and 24.6 +/- 6.4 with the increasing infusion rate. Steady-state M/S values were 6-fold higher than the predicted M/S value (4.19). Hence, cimetidine transport into rabbit milk appears to be governed by diffusion, whereas cimetidine transfer into rat milk may involve active transport. PMID- 1602397 TI - Chronic epinephrine treatment fails to alter prejunctional adrenoceptor modulation of sympathetic neurotransmission in the rat mesentery. AB - Rats were treated chronically with epinephrine (EPI-T; 100 micrograms/kg/hr, s.c.) for 6 days. On day 6 of treatment, the rats were anesthetized and the mesenteric vascular bed was isolated and perfused with Krebs' bicarbonate buffer containing cocaine (10 microM) and corticosterone (40 microM). Stimulus-induced (2 Hz, 120 pulses) overflow of neurotransmitter and its modulation by prejunctional adrenoceptors was studied. After chronic exposure to EPI, 50% of the mesenteric catecholamine stores consisted of EPI with no increase in total catecholamine content as compared to the control group (C). Absolute and fractional overflows of catecholamines upon periarterial nerve stimulation (2 Hz, 1 min) were not significantly different in the two groups. Beta adrenoceptor blockade by propranolol (10(-10) to 10(-6) M) did not alter the overflow of catecholamines. Alpha adrenoceptor blockade by phentolamine (10(-5) M) increased neurotransmitter overflow in both EPI-T and C groups. However, there was no significant difference in total catecholamine overflows between the two groups. Moreover, in the presence of phentolamine, propranolol (10(-6) M) remained without effect on overflow in both groups. These data suggest that EPI-T did not significantly increase the stimulus-induced overflow of catecholamines in the rat mesentery, nor did EPI-T result in prejunctional beta adrenoceptor modulation of neurotransmitter release in the mesenteric vascular bed. PMID- 1602398 TI - Cardiac angiotensin receptors: effects of selective angiotensin II receptor antagonists, DUP 753 and PD 121981, in rabbit heart. AB - Angiotensin II (AII) elicits a positive inotropic response in cardiac muscle preparations from several species including humans. The purpose of this study was to characterize the AII binding sites and inotropic responses in rabbit ventricle using the selective AII receptor antagonists/ligands, DuP 753 (AT1) and PD 121981 (AT2). Biphasic displacement of specific 125I-Sar1,Ile8-AII binding was observed with both DuP 753 and PD 121981, suggesting the presence of two AII binding sites. The high affinity site for DuP 753 (29 nM) was a low affinity site for PD 121981 (91 microM), and the high affinity site for PD 121981 (78 nM) was a low affinity site for DuP 753 (81 microM). Of the specific AII binding, 70% was DuP 753 (AT1)-sensitive sites. Positive inotropic responses to AII in isolated papillary muscles from rabbit heart were antagonized competitively by both DuP 753 and PD 121981. The potencies of DuP 753 (pA2 = 7.99) and PD 121981 (pA2 = 4.28) to antagonize AII inotropic responses were similar to their potencies to displace 125I-Sar1,Ile8-AII from AT1 sites. There was no apparent functional consequence of AII interaction with AT2 site. Inotropic responses to isoproterenol were unaffected by DuP 753 and PD 121981. Therefore, there are two binding sites for AII in rabbit ventricle; however, only one site, AT1, participates in the inotropic response to AII. The roles of these receptor subtypes in other cardiac responses to AII have yet to be determined. Also, DuP 753 and PD 121981 are useful tools to study these two AII binding sites in cardiac preparations. PMID- 1602399 TI - Fourphit: a selective probe for the methylphenidate binding site on the dopamine transporter. AB - Fourphit, a phencyclidine derivative containing an isothiocyanate substitution at the 4-position of the piperidine ring, inhibits the binding of the radiolabeled psychomotor stimulant, [3H]methylphenidate, to sites on the dopamine transport complex in membranes prepared from the crude synaptosomal fraction of rat striatal tissue with an IC50 of 7.1 microM. The inhibition caused by Fourphit is irreversible and is associated with a decrease in the Bmax, but not the KD, of [3H]methylphenidate binding. Pretreatment with saturating concentrations of unlabeled methylphenidate effected a modest (but statistically significant) protection of the stimulant binding site from inactivation by Fourphit, indicating that the acylating phencyclidine derivative may act directly at this site. Preincubation with Fourphit rather than vehicle did not alter the dissociation rate of [3H]methylphenidate when measured in the presence of excess amfonelic acid, nor was any difference detected in the off-rate of [3H]methylphenidate when excess Fourphit was substituted for excess unlabeled methylphenidate as the displacing agent. This lack of effect on the dissociation kinetics of [3H]methylphenidate provides further evidence that Fourphit does not act allosterically at the methylphenidate binding site. Unlike Metaphit (an isomer of Fourphit containing the isothiocyanate moiety at the meta position of the aromatic ring), Fourphit can discriminate between the methylphenidate binding site and the phencyclidine binding site associated with the N-methyl-D-aspartate receptor: Metaphit irreversibly inactivates both binding sites, whereas Fourphit binds reversibly to the phencyclidine binding site. The data suggest that Fourphit may be useful as a relatively selective affinity label for the site on the dopamine transport complex recognized by methylphenidate and other psychomotor stimulants. PMID- 1602400 TI - Two models of peripheral sympathetic autoregulation: role of neuronal histamine. AB - We have studied the influence of a peripheral histamine-containing neuronal system on the sympathetic activity of the rat vas deferens. Chronic surgical interruptions of the sympathetic structures involving the adjacent histamine containing neuronal system cause changes of sympathetic activity, as measured by the rate of disappearance of norepinephrine after reserpine administration to the awake rat. Sympathetic ganglionectomy performed on either side causes an enhancement of the sympathetic activity in the contralateral vas deferens. When the decussation of histamine-containing pathways is surgically interrupted (interganglionic section), a bilateral enhancement of sympathetic activity occurs. The histamine-containing neuronal system seems to exert a contralateral reciprocal inhibitory modulation of sympathetic activity at the vas deferens. This modulation is evoked by nervous impulses traveling in the preganglionic fiber because enhancement of sympathetic activity due to contralateral ganglionectomy is suppressed by ipsilateral decentralization. No compensatory reflexes of central origin are observed. Sympathetic enhancement due to interruption of histamine-containing nervous pathways is reversed by i.v. infusion of histamine. An H-1 or H-2 histamine receptor antagonist does not have any effect on the vas deferens sympathetic activity of the intact rat. In the heart of the deafferentated dog, removal of the left stellate sympathetic ganglion causes facilitation of the chronotropic responses induced by stimulation of the right sympathetic postganglionic nerve, also suggesting a peripheral contralateral inhibitory modulation of sympathetic activity at the heart. It appears from all these findings that a peripheral inhibitory reflex is evoked when sympathetic activity is enhanced, thus contributing to maintaining homeostasis. PMID- 1602401 TI - Regional differences in the effects of septic shock on vascular reactivity in the rabbit. AB - Experiments were performed to investigate the vascular reactivity in both large and resistance artery preparations from an animal model of septic shock. New Zealand White rabbits were injected with a priming dose of Escherichia coli lipopolysaccharide (LPS), 15 micrograms/kg i.v., 18 hr before an i.v. dose of 200 to 2000 micrograms/kg under pentobarbital anesthesia. The second LPS challenge dropped mean blood pressure from 79 +/- 4 to 27 +/- 5 mm Hg in approximately 1 hr. At this time animals were sacrificed with the central ear arteries and kidneys being isolated for alignment in a Krebs-bicarbonate buffer perfusion apparatus to monitor perfusion pressure under constant flow conditions. Individual dose-response curves (DRCs) for norepinephrine (NE) and histamine were performed to assess contractile function. For examining vascular relaxant function, DRCs for methacholine (MC) and nitroprusside (NP) were conducted during a submaximal infusion of NE. The DRCs to NE and histamine were shifted to the right by 2- and 2.7-fold, respectively, in isolated ear artery preparations from LPS-treated vs. vehicle-treated animals. There was no difference in contractile function (using NE) in the two groups of perfused kidneys. The relaxation DRCs to MC were similar in the ear artery preparations from the two treatment groups whereas, in isolated kidneys, the relaxation to MC was significantly attenuated, by an average of 26 +/- 2% at each of six doses, in preparations from LPS-treated animals. The relaxation to NP was similar between the LPS- and vehicle-treated animals in the ear artery and kidney preparations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602402 TI - Endotoxin-induced activation of cerebral catecholamine and serotonin metabolism: comparison with interleukin-1. AB - Administration of either endotoxin (lipopolysaccharide, LPS) or interleukin-1 (IL 1) activates the hypothalamic-pituitary-adrenal axis and cerebral catecholamine systems. Because LPS can stimulate IL-1 production in vivo, it is possible that the effects of LPS are mediated by IL-1. This hypothesis was evaluated by comparing the neurochemical and corticosterone responses to i.p. LPS and IL-1. In addition, the possibility that LPS acts by penetrating the brain was examined by comparing the neurochemical responses to i.p. and i.c.v. administration. Intraperitoneal injection of LPS increased mouse brain concentrations of the norepinephrine catabolite, 3-methoxy,4-hydroxyphenylethyleneglycol (MHPG), the dopamine catabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), and the 5 hydroxytryptamine catabolite, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan in all brain regions examined. By contrast, i.p. IL-1 alpha and IL-1 beta increased cerebral concentrations of MHPG, 5-HIAA and tryptophan, but not DOPAC. The MHPG responses to IL-1 were substantially greater in hypothalamus than in other brain regions, whereas those to LPS were less regionally specific. The minimum effective doses of LPS and IL-1 were around 1 microgram and 10 ng, respectively. After i.p. LPS, plasma concentrations of corticosterone, DOPAC and MHPG peaked around 2 hr, whereas peak concentrations of tryptophan and 5-HIAA occurred around 8 hr. Intracerebroventricular LPS also elevated plasma corticosterone and cerebral concentrations of MHPG and 5-HIAA, but DOPAC was unchanged. LPS was not substantially more potent i.c.v. than i.p.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602403 TI - Developmental differences in erythropoietin pharmacokinetics: increased clearance and distribution in fetal and neonatal sheep. AB - Although erythropoietin (Ep) is considered the primary hormone responsible for erythrocyte production throughout development, the administration of recombinant human Ep (rhEp) to premature human neonates has, thus far, been ineffective in the prevention and treatment of their anemia. To determine if developmental pharmacokinetic differences might in part be responsible for this lack of efficacy, Ep pharmacokinetic studies were carried out in four groups of sheep: late gestation fetal, neonatal, adult and pregnant. After i.v. bolus injection of tracer amounts of the biologically active [125I]rhEp, plasma [125I]rhEp was measured using a sensitive and specific Ep immunoprecipitation assay. Pharmacokinetic parameters were derived using noncompartmental system analysis. Significantly greater clearances, shorter half-lives, shorter residence times, greater distribution volumes and greater Ep production rates were found in the fetal and neonatal groups compared to pregnant and nonpregnant adults (P less than .01). These developmental differences likely reflect more rapid metabolism and greater distribution of Ep in less mature individuals. As such, they could result in a reduction in Ep's erythropoietic effect similar to that reported in premature infants. We speculate that treatment of anemic premature neonates using rhEp doses shown to be effective in adults may be inadequate. PMID- 1602404 TI - Sympathoadrenal stimulation, not endothelin, plays a role in acute pressor response to cyclosporine in anesthetized rats. AB - The possible role of sympathoadrenal stimulation and endothelin release in cyclosporine (CS)-induced hypertension was ascertained in intact and pithed rats. CS (20 and 40 mg/kg), administered by i.v. infusion over 10 min, produced a dose dependent increase in blood pressure: 19 +/- 5 and 31 +/- 2 mm Hg in intact rats and 13 +/- 4 and 18 +/- 2 mm Hg in pithed rats. In intact rats, pretreatment with reserpine (5 mg/kg, i.p.) or hexamethonium (10 mg/kg, i.v.) greatly blunted the pressor responses to CS (40 mg/kg) (7 +/- 3 and 11 +/- 2 mm Hg, respectively). In pithed rats, the blood pressure responses to CS (40 mg/kg) were significantly impaired, but were not further modified by phenoxybenzamine (3 mg/kg, i.v.), whereas adrenalectomy completely abolished the CS-induced pressor responses (0 +/ 1 mm Hg). CS (40 mg/kg) did not potentiate pressor responses to sympathetic nerve stimulation (0.1 and 0.3 Hz) or vasoconstrictors, including angiotensin II (0.03 microgram/kg, i.v.), phenylephrine (1 microgram/kg, i.v.) and arginine vasopressin (0.075 microgram/kg) in pithed rats. In addition, CS (40 mg/kg, i.v.) did not cause elevation of plasma immunoreactive endothelin-1 and -3. Furthermore, phosphoramidon (0.25 mg/kg/min x 30) abolished pressor response to big endothelin-1 (5 micrograms/kg, i.v.) but failed to affect CS-induced hypertension. It is concluded that the acute blood pressure response to CS manifests great dependence on sympathetic nervous system but appears independent of endothelin release. PMID- 1602405 TI - The origins of the human immunodeficiency viruses: an update. AB - In 1981 a new acquired immunodeficiency syndrome was first described. The disease has a 100% mortality rate and over 359,000 cases have been reported to the WHO from 162 countries. The WHO estimates that the cumulative global total of AIDS cases as of early 1991 is more than 1.5 million. The dental profession, in line with other health care professions, is involved with guiding rational efforts to stop transmission and with developing effective means of treatment and prevention. This paper reviews the nature of the virus, its possible origins, and the implications of such origins for treatment and prevention of the disease. PMID- 1602406 TI - Alveolar bone remodeling after tooth extraction in normal and osteopetrotic (ia) rats. AB - One of the osteopetrotic mutations in the rat, incisors-absent (ia), exhibits generalized skeletal sclerosis and failure or delay of tooth eruption, characteristics of other osteopetrotic mutations. Osteopetrosis in ia rats is known to be due to a reduction in bone resorption, the result of the inability of ia osteoclasts to elaborate a ruffled border. During healing of extraction wounds, especially the initial period, osteoclastic resorption of alveolar bone is considered to be a significant feature, followed by new bone formation. We have studied extraction wound healing in osteopetrotic (ia) rats histologically in order to determine if their systemic reduction in bone resorption changes the sequence or rate of alveolar bone healing within and outside the socket after tooth extraction, In ia rats, the healing process was delayed in comparison to that of normal rats. Many osteoclasts were observed on the surface of alveolar bone, but there was little evidence of resorption. Bone formation in the socket following bone resorption was reduced and the newly formed trabeculae were irregular. In contrast, the quantity of resorption-independent (periosteal) new bone formation outside the socket was exaggerated compared to normal animals. These data indicate that the disturbance of new bone formation in the socket is probably related to the reduction in osteoclastic bone resorption. PMID- 1602407 TI - Ectomesenchyme of ameloblastic fibroma reveals a characteristic distribution of extracellular matrix proteins. AB - The distribution of collagens type I, IV and VI, procollagen type III and of undulin was studied in four cases of ameloblastic fibroma (AF). The ectomesenchyme of AF revealed an as yet unobserved organization of these extracellular matrix proteins with collagen type VI clearly predominating over collagen type I, procollagen type III and undulin, that showed a weak and amorphous distribution throughout the tumor stroma. Undulin, a glycoprotein that is associated with mature collagen fibrils and with differentiated tissues, was not detectable in the tumor stroma of AF except for a slow expression around capillaries and in areas with a high cellularity. We could demonstrate that the characteristics of extracellular matrix composition allowed a clear distinction between the ectomesenchyme of AF and the adjacent normal mesenchymal stroma. Due to the specific staining patterns it was possible to detect epithelial tumor islands outside the typical ectomesenchymal stroma. Our findings furthermore indicate that epithelial cells of AF invade the adjacent normal mesenchyme possibly inducing de novo formation of ectomesenchymal tumor stroma. PMID- 1602408 TI - Histopathologic and ultrastructural studies of oral mucosa with Candida infection. AB - Eighteen oral mucosal biopsies with Candida infection were studied with light and electron microscopy. Under light microscopy, candidal infected oral mucosa was classified with epithelial hyperplasia, 15 cases and epithelial dysplasia, three cases. Four of 15 epithelial hyperplasias showed marked parakeratosis, and high grade acanthosis with many eosinophilic cells in the spinous cell layers. Epithelial dysplasia was characterized by atrophy of the spinous cell layers and increased nucleocytoplasmic ratio in the basal cell layers. Ultrastructurally, candidal infected oral mucosa showed numerous small desmosomes and the interdigitation of cytoplasmic membranes between spinous cells in both epithelial hyperplasia and epithelial dysplasia. Moreover, eosinophilic spinous cells, observed predominantly in epithelial hyperplasia showed intricate arrangement of dense tonofibrils. These ultrastructural findings seemed to give rise to mechanical strength between spinous cells in oral mucous epithelium with Candida infection. Results in this study suggest that excessive hyperplasia of candidal infected oral mucosa might be a protective reaction to the invasion of candidal pseudohyphae, but not associated with precancerous conditions. PMID- 1602409 TI - T-lymphocyte subsets in oral mucosa of patients with recurrent aphthous ulceration. AB - In the present study, the proportion of mononuclear cells and percentages of CD4+ (OKT4+) and CD8+ (OKT8+) were determined in clinically healthy buccal mucosa in patients with recurrent minor aphthous ulceration (RAU) (n = 43) during active and inactive disease as compared with RAU-free controls (n = 15). In lamina propria, the total number of mononuclear cells and subset percentages were determined histologically and immunohistochemically. Mononuclear cell counts in patient specimens were significantly lower than in the control group. CD4+ percentages were not significantly different between controls and patients. CD8+ percentages of the patients were significantly increased during active RAU, but not during inactive RAU as compared with controls. In proportion to the total number of mononuclear cells, CD4+ and CD8+ cell counts per 0.25 mm2 were significantly lower in the patients during both active and inactive disease as compared with controls. Thus, RAU seems characterized by reduced numbers of mononuclear cells, including T-lymphocytopenia in the oral mucosa as such, features that appear more pronounced during active disease than during quiescence. PMID- 1602410 TI - Cyclosporin-A increases type I procollagen production and mRNA level in human gingival fibroblasts in vitro. AB - In order to study the pathogenesis of gingival overgrowth induced by the immunosuppressive drug cyclosporine-A (CyA), we investigated its effect on 3H thymidine incorporation and on collagen production and mRNA levels in fibroblast cultures obtained from normal human gingiva. At concentrations of 100, 500 and 1000 ng/ml, CyA did not modify thymidine incorporation after 24 and 72 h of incubation. However, after 24 h it significantly increased the level of 3H proline-containing proteins in the medium. In addition, CyA increased alpha procollagen chains by up to three times. This CyA-induced change was related to a rise in the level of type I procollagen. The CyA effect on fibroblasts was markedly reduced by cycloheximide, an inhibitor of protein synthesis, and it correlated well with an increase of type I procollagen mRNA. Overall, our data indicate a direct stimulatory action of CyA on collagen synthesis, but not on DNA synthesis, in human gingival fibroblasts. PMID- 1602411 TI - Scanning electron microscopic study of primary teeth in X-linked amelogenesis imperfecta. AB - Exfoliated primary teeth from a boy and a girl from a family with X-linked amelogenesis imperfecta (XAI) were studied by scanning electron microscopy. Teeth from the boy featured multiple shallow depressions on the enamel surface interspersed with deeper tubular voids. Shallow depressions and similar tubular defects were also apparent in control teeth from an unaffected individual but these were less frequent, irregularly distributed and less marked. Teeth from the heterozygous girl had broad furrows running longitudinally from the cusp(s) of the tooth cervically. These furrows were formed by a series of saucerized depressions which merged together in some areas. The bases of these depressions featured tubular voids extending into the enamel. These similar voids in teeth from both boy and girl probably represent enamel prism spaces vacant because of defective enamel protein synthesis and/or mineralization. Although the scanning electron microscopic features of teeth from females observed in this and previous studies of XAI differ, the enamel appears to be more similar in males with differing clinical XAI phenotypes. PMID- 1602412 TI - [A quantitative approach to understand the ultramicro-structure responsible for input mechanism in excitation-contraction (E-C) coupling, on the basis of physio morphological observations]. AB - Our morphophysiological studies using concanavalin A-ferritin (Con A-F) have indicated that: (1) an out- and up-ward movement of a movable structure at the luminal surface-portion of the T-tubular membrane opposite the feet initiates contraction; (2) the grade of the movement depends on that of depolarization; (3) the movable structure is essentially a 'moving arm', which is fixed in wall of T tubules at its fixed end and is able to be bound to the Con A-moiety of Con A-F particle about at its free end. Calculation based on molecular morphology and behaviour of Con A-F particle revealed following points: If (a) the origin of coordinate be the intersection of longitudinal center line of foot and the surface of T-tubular membrane in the transverse section of the tubules, (b) the fixed point of the arm is exactly on the surface of T-tubular membrane, and (c) the movement takes place in the transverse direction to the longitudinal axis of T-tubules, (1) the location of the center point of the movement of the moving arm is at 5.4 nm in the outside direction from the origin, (2) the arm is about 4 nm in length and moves by about 2.4 nm up- and out-ward at its free end upon about complete depolarization. PMID- 1602413 TI - Student voice. PMID- 1602414 TI - Diabetes in the elderly. Techniques in management and basic care. AB - The diabetic patient in general faces tremendous challenges: self-medication, diet changes, exercise regime, and blood glucose monitoring. In addition, the elderly patient with diabetes has other unique needs. With education, encouragement and support, the diabetic today can lead lives as actively as persons without the disease. PMID- 1602415 TI - Interferon not recommended for treatment of HIV infections. PMID- 1602416 TI - Intervention in falls among the elderly. PMID- 1602417 TI - How to make the most of your charting. PMID- 1602418 TI - Bedside nursing. Where treasures abound. PMID- 1602419 TI - ADN program offers accelerated course for licensed practical nurses. PMID- 1602420 TI - Pneumocystis carinii in AIDS patients. PMID- 1602421 TI - Continuing nursing education. PMID- 1602422 TI - Computerized adaptive testing for NCLEX-PN. PMID- 1602423 TI - Valuing our "customers". PMID- 1602424 TI - Advance directives provide answers for tough questions. AB - Will advance directives provide an effective means of assuring that previously written decisions will be honored by health care providers if the patient becomes incompetent or terminally ill? This and other questions are posed in the following article. The Patient Self-Determination Act of 1990 mandates that all health care providers receiving federal reimbursement for services provide information to each patient and offer the option of executing an advance directive for health care decisions. The author presents an overview of two studies about advance directives as reported in the New England Journal of Medicine. PMID- 1602425 TI - Violence: amending a social norm. PMID- 1602426 TI - Effects of two treatment techniques on delay and vigilance tasks with attention deficit hyperactive disorder (ADHD) children. AB - In this study, we examined the effects of two treatment techniques under on medication and off-medication conditions on the hyperactive behavior patterns of children. Three groups of subjects were compared: a control group, a behavior modification group, and a cognitive training group. The Gordon Diagnostic System (Gordon, McClure, & Post, 1986) was used to assess the subjects at the initial screening, during treatment without medication, and during treatment with medication. The two medication conditions were counterbalanced during the second and third testing sessions. Results showed that when the cognitive intervention was combined with medication, there was a significant improvement in the subjects' ability to delay impulsive responding. However, no significant effects were seen for sustained vigilance for either the behavioral or cognitive groups. Parents rated children in the cognitive group significantly higher than those in the control group. PMID- 1602427 TI - How to deal with sexual acting-out on the child psychiatric inpatient ward. AB - 1. Although the management of sexually abused children is not new, a comprehensive approach is often lacking, especially as it pertains to dealing with sexually acting-out children. 2. In addition to the usual social work measures of child protection, a program of developmentally and psychoeducationally based interventions supplemented by behavioral techniques were found to be most effective. 3. Acting-out children often provoke reactions of rage, betrayal, and impotence among the staff. Discussions of interventions must take into account the staff's own philosophy about how sexuality should be taught to these children. 4. The treatment team leader must decide whether the sexual acting-out among children is due to active solicitation from sexually abused children, delinquent acting-out, or age-appropriate exploration. PMID- 1602428 TI - Psychiatric mental health consultation and nursing in the United Arab Emirates. AB - 1. Our "mission" was preparing psychiatric services for the anticipated high number of allied casualties; providing clinical, educational, and developmental support to the host nation; and maintaining diplomatic relations within the hospital and surrounding community. 2. Because of cultural differences, the hospital staff were uneasy about some of the inservice classes. US staff were taught the importance of refusing to succumb to "the illusion of color blindness." 3. With the support of the host, we took leadership in receiving and training the casualties of the war. Psychiatric services were provided to allied troops as well as the citizens of Dubai. PMID- 1602430 TI - Transition from the hospital to the community: small group program. AB - 1. Clients in a psychiatric hospital often experience loss of control over their lives and dissatisfaction with their quality of living. A small group rehabilitation program can counteract the effects of institutionalization and restore a sense of mastery to chronic psychiatric clients. 2. The therapeutic nurse-client relationship provides consistency and stability for clients who must cope with the stress of the mental health system and the transition to a community setting. 3. The program strives to restore individuals' self-confidence and dignity, improve their quality of life, and decrease the frequency and length of hospitalization. PMID- 1602429 TI - Postpartum affective disorders: incidence and treatment. AB - 1. Postpartum depression is a culture-bound syndrome found in Western societies. The lack of supportive rites and rituals for postpartum women shape depressive symptoms. 2. Postpartum depression is a term used for three distinct syndromes: postpartum "blues," postpartum psychosis, and postpartum depression. 3. Treatment issues surrounding each postpartum affective disorder are different and require education and support of family members as well as postpartum women. PMID- 1602431 TI - APNA semantics. PMID- 1602432 TI - Waking from the nightmare of schizophrenia. PMID- 1602433 TI - A peer supervision group: put countertransference to work. AB - 1. As the nurse-patient relationship evolves through a series of ongoing interactions, both participants become "known" and stir in each other a range of positive and negative emotional reactions. 2. When working with severely psychologically disturbed patients, the nurse's affective and behavioral response can be valuable clues to understanding the patient's early experiences that contribute to the pattern of relatedness and to the formulation of change, enhancing therapeutic interactions. 3. The goals of the countertransference peer supervision group were to recognize unconscious countertransference reactions; unravel the origin and meaning of those countertransference reactions; and collaboratively develop therapeutic nursing interventions. PMID- 1602434 TI - The art of therapeutic drawing. Helping chronic trauma survivors. AB - 1. Survivors of chronic trauma, who may have survived hundreds of episodes of battering and abuse, have no gauge of what is normal and continue to live in the same emotional climate. 2. The coping patterns that are a result of chronic trauma are below the level of awareness and prevent healthy adaptation. 3. The inclusion of expressive techniques, such as therapeutic drawing, can be used to facilitate the emotional work of chronic trauma issues. PMID- 1602435 TI - [Stereotaxy, MRI and independent computer. 85 punctures]. AB - After 150 stereotactic biopsy with CT, the team of Val-de-Grace has made these ones with MRI and simulation of the complete procedure with an independent computer. The result of 85 biopsies is reported. This one imply the acquisition of 3DFT millimetrics slices, the transfer by Ethernet network on a computer where a specific software treat the data and allow to establish the better course for the needle biopsy. The constraints of quality are very important and some test must be executed. The diagnosis are established, avoiding an unless trepanation. PMID- 1602436 TI - [MRI of malformative syringomyelia. Descriptive and developmental aspect]. AB - 132 cases of malformative syringomyelia have been studied at the C.I.E.R.M. (Interdepartmental Magnetic Resonance Center) of Bicetre Hospital. The authors describe their technique for the exploration on the cord in case of suspected intramedullary cavitation, and emphasize the morphological and evolutive aspects of these abnormalities, whether they have been operated or not. PMID- 1602437 TI - [Pseudo-aneurysm of the internal carotid artery]. AB - The authors recall the anatomy of the deep neck spaces and report the case of a 3 year-old girl with a parapharyngeal abscess followed by a pseudo-aneurism of the carotide artery. Ultrasonography, CT scan and angiography findings are described. This case puts in mind of the seriousness of neck abscesses. Each specific anatomical location must be definite for a better therapeutic approach on account of hemorrhagic risks of parapharyngeal abscesses. PMID- 1602438 TI - [Amebic abscess of the caudate lobe. An uncommon topographic form]. AB - Amebic liver abscess is the most common extraintestinal complication of invasive amebiasis. Amebic abscess is most often located in the right lobe of the liver which is affected four times as often as the left lobe. Location in the caudate lobe is exceptional. We report herein a case of amebic abscess located in the caudate lobe. PMID- 1602439 TI - [Radiological study of firearm projectiles. 2. Projectiles of smooth-bore guns]. PMID- 1602440 TI - [National survey on urinary incontinence]. PMID- 1602441 TI - [How to make a conference]. PMID- 1602442 TI - [Nephropathy caused by iodinated contrast media and diabetes]. PMID- 1602443 TI - [Iodinated contrast media and diabetes mellitus]. PMID- 1602444 TI - [The American College of Radiology]. PMID- 1602445 TI - [X-ray computed tomographic study of the ethmoid bone and middle meatus. III. Application to chronic infectious sinus pathology]. AB - As nasal endoscopy, high resolution CT is a part of the chronic rhinosinusitis pre-operative assessment. It shows, thanks to a precise and anatomical study of the ethmoid and sinusal draining, the extension of the diseases and the local morphological variations which predispose to chronic diseases. The main aspects of chronic sinusitis, nasal polyposis and fungal maxillary sinus diseases are reported. The frequency of individual morphological variations and the mucosal changes due to a nasal cycle require a great care in the interpretation of the diseases. PMID- 1602446 TI - [Protecting research workers in a specialty providing services. A model for radiological science]. PMID- 1602447 TI - [Towards another diagnostic approach of peripheral pulmonary masses. Ultrasound guided puncture]. AB - In a series of 50 patients with lung lesions touching the thoracic wall, percutaneous ultrasonically guided needle aspiration yielded a pathological diagnosis in 44 cases (sensitivity: 88%). The histological diagnosis of malignant lesion could be confirmed in 41 of these 44 patients. In this group of patients with neoplasia the diagnosis obtained by extemporaneous cytology was compared with that obtained by lung biopsy: the diagnostic sensitivity of cytology proved to be higher than that of biopsy (86.36% and 65.90% respectively). Using the two methods concomitantly increased sensitivity up to 93.18%. A pathological diagnosis could be obtained in 3 out of the 6 patients in this series who had benign lesions. PMID- 1602448 TI - [Scintigraphy of the lacrimal ducts. Value of the lateral incidence in postoperative period]. AB - Lacrimal scintillography, a simple, non traumatic, and physiological method, has been for a long time an useful exploration in the study excretory pathology. It allows an accurate diagnosis especially in the case of functional stenosis and, due to its ability to indicate the exact seat of obstruction, this technique is able to determine the surgical treatment required. This study underlines the contribution of lacrimal scintillography in the control of surgical anastomosis permeability, because of a modification in the initial technique: the use of scintillography in employing the lateral view rather than the front view, usually used, permits a better visualisation of the new surgically created excretory passage, particularly in the posterior area of nasal fossae. PMID- 1602449 TI - [Imaging of cervical and thoracic chordoma. Apropos of 2 cases]. AB - Chordoma is a rare tumor in spine. Two cases, exceptional in adolescents, are reported. The clinical evolution is slow and progressive. CT shows a lobulated tumor, precises the degree of vertebral osteolysis and detects intra-tumoral calcifications. MRI is useful to determine especially in high in soft tissues and the vertebral canal. Arteriography is realised in pre-operative time and permits an embolization when the tumor is hypervascularised. PMID- 1602450 TI - [Thrombosis of the cerebral veins. X-ray computed tomography and MRI imaging. 11 cases]. AB - 11 cases of cerebral venous thrombosis in adults are reported. Main clinical signs are: intracranial hypertension (headache, nausea, papilledema in 7 cases, loss of consciousness in 6 cases, neurological deficit in 6 cases, seizure in 4 cases. 1 patient is dead, who did not receive heparin treatment. Delay before diagnosis is between 2 and 20 days, and is shortened when arteriography or MRI are available and prescribed. At least one (or several) CT examination was performed in 10 patients. Direct signs of thrombosis are uneasily detected without contrast injection, seen here in 4 cases. Empty delta sign is observed in 7 patients, lately in 4 cases, and once only afterwards. Cerebral infarction is visualized in 7 cases over 10. Its features frequently seem evocative for cerebral venous thrombosis: triangularin 4 cases or nodular shape in 3 cases with hemorragic infarct in 7 cases, with bilateral topography in 6 cases, in frontal or central areas in 7 cases. 6 patients had a MRI examination. All cerebral infarctions appeared haemorragical, even at early stages. During subacute period, venous thrombosis is constantly and easily detected by the mean of methemoglobin high signal intensity on T1 weighted images. The prediagnosis delay is short, without necessity of arteriography. MRI should take the place of CT and arteriography in investigation of a clinically suspected cerebral venous thrombosis. PMID- 1602451 TI - [Aseptic osteonecrosis of the knee induced by corticoids. MRI aspects]. AB - Authors report the results of a series of 29 knees examined by magnetic resonance imaging in 16 patients subjected to a long-term corticosteroid therapy (6 systemic lupus erythematosus and 10 kidney transplanted people). Abnormal signals of condyles or tibial plateaus were observed in 12 patients (19 knees). Lesions, which were asymptomatic in 37% of the cases studied, mostly showed (12/24 condyles) a fatty signal area marked out by a hypointense signal strip in T1 edged with a hyperintense signal in T2. Some developed lesions were hypointense whichever the sequence. Our study confirmed the frequency of the lateral condyle involvement (60%) and the bilateral aspect of the lesions (50%) in osteonecrosis of the condyles following the corticosteroid therapy. The associated lesions of articular surfaces (3 cases) could be well assessed through magnetic resonance imaging on T2 or T2* weighted images. In two cases, the abnormal signals of the condyles suggesting a medullary edema (hypointense signal in T1 and hyperintense signal in T2) spontaneously disappeared 6 and 9 months after their discovery. Abnormal signals related to medullary infarcts (10 knees) were always associated with abnormal condyles. Most time their aspect in magnetic resonance imaging, except old calcified lesions, was characteristic: serpiginous hypointense signal isolating areas of fatty signal edged with a hyperintense signal strip in T2. In risk patients, magnetic resonance imaging allows early detecting knee necroses, precising the extent of epiphyseal and metaphyso-diaphyseal lesions and their impact on articular surfaces. PMID- 1602452 TI - [Radiologic diagnosis of renal cortical necrosis. Apropos of a case and review of the literature]. AB - One case of renal cortical necrosis is reported. The results of ultrasound and angiographic imaging and the relevant literature are reviewed. The examinations, particularly selective angiography, are of great interest in the diagnostic and in the etiology of this disease. PMID- 1602454 TI - [Is the hybridization of French medical language inevitable?]. PMID- 1602453 TI - [Use of a constant-flow 2-phase injector for abdominal scanners in 60 patients]. AB - The intravenous injection of a contrast medium is carried out in more than 80% of all the patients undergoing abdominal CT. The use of a constant-flow two-phase injector has several advantages in practice: possibility to vary the injections, safety, easy use, reproducibility, overall quality of the results and possibility to reduce the dose of contrast medium. The routine use of such equipment seems to be indispensable at present. PMID- 1602455 TI - Establishment and characterization of Macaca fascicularis lymphoblastoid cell lines. AB - A panel of cynomolgus macaque lymphoblastoid cell lines (LCL) was established by transforming peripheral blood mononuclear cells (PBMC) with Herpesvirus papio (HVP), and selected lines were examined by flow cytometry. Results indicate that HVP-transformed macaque LCL are phenotypically heterogeneous and resemble human Epstein-Barr virus (EBV)-transformed LCL in the abundant expression of major histocompatibility complex (MHC) class I and class II molecules. At least some lines are of B cell origin. PMID- 1602456 TI - Survey of Saguinus mortality in a zoo colony. AB - Six years of necropsy records from a zoo colony of four tamarin species (Saguinus oedipus, S. geoffroyi, S. imperator, and S. mystax) were examined. Mean age at death was 4.0 years, average length in the colony at time of death was 3.4 years. Annual mortality rate varied between 9 and 30%. Gross necropsy findings, histopathologic, and bacteriological results indicate primary cause of death as follows: peritonitis (26%), septicemia (14%), nephritis (5%), hepatitis (5%), pneumonia (2%), and others. PMID- 1602457 TI - A prospective analysis of endometrial cycle changes by ultrasound in the female cynomolgus monkey. AB - Endometrial cycle changes in adule female cynomolgus monkeys with normal ovulatory cycles were examined prospectively by real-time ultrasound. Endometrial thickness, as measured by ultrasound, was correlated with cycle day and serum estradiol (E2) and progesterone (P4) levels. We conclude that ultrasound is a reliable method of diagnosis of endometrial cycle stage. PMID- 1602458 TI - Mortality causes of the moustached tamarin (Saguinus mystax) in captivity. AB - From January 1987 to November 1990, 125 adult Saguinus mystax died at the CRCP. Enteritis/colitis (26%), hypoglycemia/cachexia (19%), and parasitic enteritis (13%) were the most common causes of death. Less common were purulent peritonitis (9%), lobular pneumonia (8%), and hemorrhagic gastroenterocolitis (6%). These results confirm the high frequency of gastroenteric lesions reported in Callitrichidae in captivity. PMID- 1602459 TI - Spontaneous seminoma in an owl monkey in captivity. AB - An adult male Aotus nancymae maintained for breeding purposes was submitted for surgery and the left testicle was removed. The surgically removed mass was about two to three times the size of a normal adult owl monkey testicle. Grossly, on cut surface, the mass was soft, white to pale gray, and bulged above the adjacent tissue. Microscopically, the morphology of the tumor cells was consistent with a seminoma. PMID- 1602460 TI - Torsion of the colon in vervet monkeys: association with an atherogenic Western type of diet. AB - The risk of torsion of the colon in adult male vervet monkeys (Cercopithecus aethipos) increased when they were fed with an atherogenic Western-type of diet. No cases occurred in females and rapid diagnosis is necessary to prevent lethal consequences. PMID- 1602461 TI - Assessment of semen quality in a baboon (Papio anubis) breeding colony. PMID- 1602462 TI - Bacteriology of middle ear effusions. PMID- 1602463 TI - Health access Mississippi. PMID- 1602464 TI - Adjuvant therapy in primary breast cancer: defining the role of systemic therapy and radiotherapy. PMID- 1602465 TI - Homelessness and chronic mental illness in Mississippi. PMID- 1602466 TI - Diagnosis and management of sinusitis in children. PMID- 1602467 TI - AMA addresses Medicare reform issues. PMID- 1602468 TI - Breast conservation surgery "BCS" for breast cancer. PMID- 1602470 TI - Opinions on practice matters. PMID- 1602469 TI - Health access in Mississippi. PMID- 1602471 TI - Effect of active site residues in barnase on activity and stability. AB - We have mutated residues in the active site of the ribonuclease, barnase, in order to determine their effects on both enzyme activity and protein stability. Mutation of several of the positively charged residues that interact with the negatively charged RNA substrate (Lys27----Ala, Arg59----Ala and His102----Ala) causes large decreases in activity. This is accompanied, however, by an increase in stability. There is presumably electrostatic strain in the active site where positively charged side-chains are clustered. Mutation of several residues that make hydrogen bonds (Ser57----Ala, Asn58----Asp and Tyr103----Phe) causes smaller decreases in activity, but increases or has no effect on stability. Deletion of hydrogen bonding groups elsewhere in proteins has been found previously to decrease stability by 0.5 to 1.5 kcal mol-1. Conversely, we find that two mutations (Asp54----Asn and Gln104----Ala) decrease stability and increase activity. Another mutation (Glu73----Ala) decreases both activity and stability. It is clear that many residues in the active site do not contribute to stability and that for some, but not all, of the residues there is a compromise between activity and stability. This suggests that certain types of local instability may be necessary for substrate binding and catalysis by barnase. This has implications for the understanding of enzyme activity and the design of enzymes. PMID- 1602472 TI - DNA supercoiling response of the sigma 54-dependent Klebsiella pneumoniae nifL promoter in vitro. AB - Transcription from the sigma 54-dependent Klebsiella pneumoniae nifL and glnAp2 promoters is activated by the general nitrogen regulatory protein NTRC. Unlike the glnAp2 promoter, which is relatively insensitive to changes in DNA supercoiling, transcription from nifL in vitro in a chloride-based buffer is supercoiling-dependent at physiological salt concentrations. The replacement of chloride with an acetate-based buffer decreases the stringency of the nifL supercoiling response, but open complexes formed on linear nifL promoter DNA under these conditions are unstable and less extensive than those found on supercoiled (form I) DNA. We have introduced mutations in particular elements of the nifL promoter that increase its homology to glnAp2. At the wild-type nifL promoter, sigma 54-RNA polymerase makes only limited contacts with the promoter in the absence of NTRC. However, a G to T change at -26 (nifL74) allows the formation of a stable closed complex with sigma 54-holoenzyme on both linear and form I templates in the absence of the activator. The combination of C to T mutations at -3 and -1 (nifL18) increases the A+T rich nature of the melted region and stabilizes open complexes formed on linear DNA. Open complex formation as a function of superhelical density was assessed at each promoter. Formation of open complexes at glnAp2 peaks at -0.024 and declines at higher superhelical densities, whereas at the wild-type nifL promoter, open complex formation peaks at -0.067 and is not detectable at superhelical densities less than -0.032. Both the nifL74 and nifL18 mutations altered the supercoiling response, increasing the ability to form open complexes at low superhelical densities. The presence of the nifL74 and nifL18 mutations in combination further altered the response of the promoter to DNA supercoiling. These observations suggest that the promoter as a whole, and not any one promoter element, mediates the transcriptional response to DNA supercoiling. PMID- 1602473 TI - Isolation and characterization of LexA mutant repressors with enhanced DNA binding affinity. AB - The LexA repressor from Escherichia coli is a sequence-specific DNA binding protein that shows no pronounced sequence homology with any of the known structural motifs involved in DNA binding. Since little is known about how this protein interacts with DNA, we have selected and characterized a great number of intragenic, second-site mutations which restored at least partially the activity of LexA mutant repressors deficient in DNA binding. In 47 cases, the suppressor effect of these mutations was due to an Ind- phenotype leading presumably to a stabilization of the mutant protein. With one exception, these second-site mutations are all found in a small cluster (amino acid residues 80 to 85) including the LexA cleavage site between amino acid residues 84 and 85 and include both already known Ind- mutations as well as new variants like GN80, GS80, VL82 and AV84. The remaining 26 independently isolated second-site suppressor mutations all mapped within the amino-terminal DNA binding domain of LexA, at positions 22 (situated in the turn between helix 1 and helix 2) and positions 57, 59, 62, 71 and 73. These latter amino acid residues are all found beyond helix 3, in a region where we have previously identified a cluster of LexA (Def) mutant repressors. In several cases the parental LexA (Def) mutation has been removed by subcloning or site-directed mutagenesis. With one exception, these LexA variants show tighter in vivo repression than the LexA wild-type repressor. The most strongly improved variant (LexA EK71, i.e. Glu71----Lys) that shows an about threefold increased repression rate in vivo, was purified and its binding to a short consensus operator DNA fragment studied using a modified nitrocellulose filter binding assay. As expected from the in vivo data, LexA EK71 interacts more tightly with both operator and (more dramatically) with non operator DNA. A determination of the equilibrium association constants of LexA EK71 and LexA wild-type as a function of monovalent salt concentration suggests that LexA EK71 might form an additional ionic interaction with operator DNA as compared to the LexA wild-type repressor. A comparison of the binding of LexA to a non-operator DNA fragment further shows that LexA interacts with the consensus operator very selectively with a specificity factor of Ks/Kns of 1.4 x 10(6) under near-physiological salt conditions. PMID- 1602474 TI - Half-site recombinations mediated by yeast site-specific recombinases Flp and R. AB - The Flp recombinase of Saccharomyces cerevisae and the related R recombinase of Zygosaccharomyces rouxii can efficiently catalyze strand cleavage and strand exchange reactions in half recombination sites. A half-site consists of one recombinase binding element, a recombinase cleavage site on one strand and a 5' spacer hydroxyl group on the other that can initiate the strand exchange reaction. We have studied the various types of strand exchanges that half-sites can participate in. Reaction between a left half-site and a right half-site generates a full recombination site. Strand transfer between two left half-sites or between two right half-sites produces pseudo-full-sites. Strand transfer within a half-site results in a stem-loop or hairpin product. The half-site strand transfer reaction is fairly indifferent to the spacer sequence of the substrate per se and is less sensitive to variations in spacer lengths than a full-site recombination reaction. The optimal spacer length of eight to ten nucleotides observed for the Flp half-site reaction likely permits the most productive catalytic interactions between two Flp monomers bound to each of two partner half-sites. When reacted with a full-site, the half-site can give rise to a normal or reverse recombinant, corresponding to homologous or non-homologous alignments of the spacer sequences during substrate synapsis. The contrary recombination (resulting from non-homologous spacer alignment), whose level is low relative to normal recombination, is partly suppressed when the half-site spacer ends in a 5'-phosphate rather than a 5'-hydroxyl group. Thus, the early steps of recombination, namely synapsis and initial stand transfer, are not dependent on complete spacer homology between the two recombining substrates. The selection of properly aligned substrate partners must occur at the homology dependent branch migration step. In reactions containing a mixture of Flp and R half-sites, Flp and R catalyze strand transfer, almost exclusively, within or between their respective cognate substrates. However, under conditions where self crosses are inhibited, strand exchange between a Flp half-site and an R half-site appears to be stimulated by a combination of R and Flp. PMID- 1602475 TI - Half-site strand transfer by step-arrest mutants of yeast site-specific recombinase Flp. AB - The Flp recombinase of Saccharomyces cerevisae can mediate strand transfer within a half-site, between two half-sites and between a half-site and a full-site. The ability of "step-arrest" mutants of Flp to partake in half-site reactions has been examined. Arg308 variants of Flp, which show little or no strand cleavage in reactions with normal full-sites, execute significant levels of strand transfer in half-site reactions. On the other hand, His305 variants of Flp, which normally accumulate the strand cleavage product from full-sites but do not complete strand transfer, yield only minute amounts of strand transfer products from half-sites. As would be predicted, the step-arrest mutants are unable to produce "normal" or "reverse" recombinants between a half-site and a full-site. The Flp protein is able to form higher-order complexes in association with a half-site. The step arrest mutants of Flp show specific defects in forming these complexes. PMID- 1602476 TI - kfrA gene of broad host range plasmid RK2 encodes a novel DNA-binding protein. AB - The korABF operon of broad host range IncP plasmid RK2 encodes proteins that coordinate expression of many other operons and that aid plasmid stability by providing at least part of a partitioning apparatus. The kfrA gene lies downstream from this operon and its transcription is repressed by all except one of the proteins encoded by this operon (KorA, KorFI, KorFII and KorB). We report here that transcription from the kfrA promoter is autoregulated by the kfrA gene product. We have purified KfrA, which is an acidic polypeptide of 308 amino acid residues, and show that it is a site-specific DNA-binding protein whose operator overlaps the primary kfrA promoter. Deletion analysis suggests that this activity is critically dependent on the N-terminal section of KfrA, which appears to contain an alpha-helix-beta-turn-alpha-helix motif. Circular dichroism confirmed the structural prediction that KfrA is almost entirely alpha-helical. The position of predicted turns suggests that, while amino acid residues 1 to 80 may form a globular domain of four or five helices, residues 80 to 280 of KfrA may adopt an extended coiled-coil domain containing a heptad repeat segment, which is probably responsible for formation of the multimers detected by crosslinking. The possibility that this unusual structure serves a second function, for example in providing a bridge to host structures required for plasmid partitioning, is discussed. PMID- 1602477 TI - A high degree of macronuclear chromosome polymorphism is generated by variable DNA rearrangements in Paramecium primaurelia during macronuclear differentiation. AB - DNA rearrangements in Paramecium lead to the formation of macronuclear chromosomes, the sizes of which range from 50 and 800 kb (1 kb is 10(3) base pairs). This process does not appear to be a simple size reduction of the micronuclear chromosomes by specific and reproducible DNA sequence elimination and chromosomal breakage followed by chromosomal amplification. On the contrary, this process generates a variety of different, but sequence-related, macronuclear chromosomes from a unique set of micronuclear chromosomes. This paper describes an attempt to understand the nature of the diversity of the macronuclear chromosomes and the mechanisms of their production. The structure of three macronuclear chromosomes, 480, 250 and 230 kb in size, have been determined utilizing chromosome-jumping and YAC-cloning techniques. The two smallest chromosomes correspond roughly to the two halves of the longest chromosome. The main contribution to the diversity arises from the chromosomal ends and is due to variable positions of the telomere addition sites and/or to variable rearrangements of DNA sequences. The 480 kb chromosome contains a region of variable length, which is likely to be due to a variable deletion, located at the position of telomerization seen in the two small chromosomes. A model of chromosomal breakage is proposed to rationalize this result where micronuclear DNA is first amplified, broken and degraded to various extent from the newly formed ends, which subsequently are either telomerized or religated. Potential implications of these processes for gene expression is discussed. Known phenotypes that have a macronuclear determinism could be explained by this type of process. PMID- 1602478 TI - Predicting protein secondary structure content. A tandem neural network approach. AB - A priori knowledge of secondary structure content can be of great use in theoretical and experimental determination of protein structure. We present a method that uses two computer-simulated neural networks placed in "tandem" to predict the secondary structure content of water-soluble, globular proteins. The first of the two networks, NET1, predicts a protein's helix and strand content given information about the protein's amino acid composition, molecular weight and heme presence. Because NET1 contained more adjustable parameters (network weights) than learning examples, this network experienced problems with memorization, which is the inability to generalize onto new, never-seen-before examples. To overcome this problem, we designed a second network, NET2, which learned to determine when NET1 was in a state of generalization. Together, these two networks produce prediction errors as low as 5.0% and 5.6% for helix and strand content, respectively, on a set of protein crystal structures bearing little homology to those used in network training. A comparison between three other methods including a multiple linear regression analysis, a non-hidden-node network analysis and a secondary structure assignment analysis reveals that our tandem neural network scheme is, indeed, the best method for predicting secondary structure content. The results of our analysis suggest that the knowledge of sequence information is not necessary for highly accurate predictions of protein secondary structure content. PMID- 1602479 TI - DNA curvature does not require bifurcated hydrogen bonds or pyrimidine methyl groups. AB - Short tracts of the homopolymer dA.dT confer intrinsic curvature on the axis of the DNA double helix. This phenomenon is assumed to be a consequence of such tracts adopting a stable B'-DNA conformation that is distinct from B-form structure normally assumed by other DNA sequences. The more stable B' structure of dA.dT tracts has been attributed to several possible stabilizing factors: (1) optimal base stacking interactions consequent upon the high propeller twist, (2) bifurcated hydrogen bonds between adjacent dA.dT base-pairs, (3) stacking interactions involving the dT methyl groups, and finally (4) a putative spine of ordered water molecules in the minor groove. DNA oligodeoxynucleotides have been synthesized that enable these hypotheses to be tested; of particular interest is the combination of effects due to bifurcation (2) and methylation of the pyrimidines nucleotides (3). The data indicate that neither bifurcated hydrogen bonds nor pyrimidine methyl groups nor both are essential for DNA curvature. The data further suggest that the influence of the minor groove spine of hydration on the B'-formation is small. The experiments favor the hypothesis that base stacking interactions are the dominant force in stabilizing the B'-form structure. PMID- 1602480 TI - Refined crystal structure of a recombinant immunoglobulin domain and a complementarity-determining region 1-grafted mutant. AB - We report the solution of the crystal structure of a mutant of the immunoglobulin VL domain of the antibody McPC603, in which the complementarity-determining region 1 segment is replaced with that of a different antibody. The wild-type and mutant crystal structures have been refined to a crystallographic R-factor of 14.9% at a nominal resolution of 1.97 A. A detailed description of the structures is given. Crystal packing results in a dimeric association of domains, in a fashion closely resembling that of an Fv fragment. The comparison of this VL domain with the same domain in the Fab fragment of McPC603 shows that the structure of an immunoglobulin VL domain is largely independent of its mode of association, even in places where the inter-subunit contacts are not conserved between VL and VH. In all three complementarity-determining regions we observe conformations that would not have been predicted by the canonical structure hypothesis. Significant differences between the VL domain dimer and the Fab fragment in the third complementarity-determining region show that knowledge of the structure of the dimerization partner and its exact mode of association may be needed to predict the precise conformation of antigen-binding loops. PMID- 1602481 TI - Crystal structure of oxidized flavodoxin from a red alga Chondrus crispus refined at 1.8 A resolution. Description of the flavin mononucleotide binding site. AB - In order to describe the detailed conformation of the oxidized flavodoxin from a eukaryotic red alga, Chondrus crispus, the crystal structure has been refined by a restrained least-squares method. The crystallographic R factor is 0.168 for 13,899 reflections with F greater than 2 sigma F between 6.0 and 1.8 A resolution. The refined model includes 173 amino acid residues, flavin mononucleotide (FMN) and 110 water molecules. The root-mean-square deviation in bond lengths from ideal values is 0.015 A, and the mean co-ordinate error is estimated to be 0.2 A. The FMN is located at the periphery of the molecule. The orientation of the isoalloxazine ring is such that the C-7 and C-8 methyl groups are exposed to solvent and the pyrimidine moiety is buried in the protein. Three peptide segments, T8-T13, T55-T58 and D94-C103, are involved in FMN binding. The first segment of T8-T13 enfolds the phosphate group of the FMN. The three oxygen atoms in the phosphate group form extensive hydrogen bonds with amide groups of the main chain and the O gamma atoms of the side-chains in this segment. T55 O and W56 N epsilon 1 in the second segment form hydrogen bonds with O-2 in the ribityl moiety and one of the oxygen atoms in the phosphate group, respectively. The O gamma H of T58 forms a hydrogen bond with the N-5 atom in the isoalloxazine ring, which is expected to be protonated in the semiquinone form. The third segment is in contact with the isoalloxazine ring. It appears that the hydrogen bond acceptor of the NH of Asp94 in the third segment is O-2 rather than N-1 in the isoalloxazine ring. The isoalloxazine ring is flanked by the side-chains of Trp56 and Tyr98; it forms an angle of 38 degrees with the indole ring of Trp56 and is almost parallel to the benzene ring of Tyr98. The environment of the phosphate group is conserved as in other flavodoxins whereas that of the isoalloxazine ring differs. The relationship between the hydrogen bond to the N-5 in the ring and the redox potential for the oxidized/semiquinone couple is discussed. PMID- 1602482 TI - Crystal structure of yeast Cu,Zn superoxide dismutase. Crystallographic refinement at 2.5 A resolution. AB - The structure of Cu,Zn yeast superoxide dismutase has been determined to 2.5 A resolution. The enzyme crystallizes in the P2(1)2(1)2 space group with two dimeric enzyme molecules per asymmetric unit. The structure has been solved by molecular replacement techniques using the dimer of the bovine enzyme as the search model, and refined by molecular dynamics with crystallographic pseudo energy terms, followed by conventional crystallographic restrained refinement. The R-factor for 32,088 unique reflections in the 10.0 to 2.5 A resolution range (98.2% of all possible reflections) is 0.158 for a model comprising two protein dimers and 516 bound solvent molecules, with a root-mean-square deviation of 0.016 A from the ideal bond lengths, and an average B-factor value of 29.9 A2. A dimeric molecule of the enzyme is composed of two identical subunits related by a non-crystallographic 2-fold axis. Each subunit (153 amino acid residues) has as its structural scaffolding a flattened antiparallel eight-stranded beta-barrel, plus three external loops. The overall three-dimensional structure is quite similar to the phylogenetically distant bovine superoxide dismutase (55% amino acid homology), the largest deviations can be observed in the regions of amino acid insertions. The major insertion site hosting residues Ser25A and Gly25B, occurs in the 2,3 beta-turn between strands 2b and 3c, resulting in the structural perturbations of the two neighbouring strands. The second insertion site, at the end of the 3c beta-strand in the wide Greek-key loop, hosts the Asn35A residue, having an evident effect on the structure of the loop and possibly on the neighbouring 5,4 beta-turn. The salt bridge Arg77-Asp99 and the disulphide bridge Cys55-Cys144 stabilize the loop regions containing the metal ligands. The stereochemistry of the two metal centres is conserved, with respect to the bovine enzyme. The Cu2+ ligands show an uneven distortion from a square plane, while Zn2+ co-ordination geometry is distorted tetrahedral. The imidazole ring of the His61 residue forms a bridge between Cu and Zn ions. A solvent peak compatible with a fifth ligand is observed 2.0 A away from the copper in the active site channel, which is filled by ordered water molecules that possibly contribute to the stability and function of the enzyme. The charged residues responsible for the electrostatic guidance of the substrate to the active site (Glu130, Glu131, Lys134 and Arg141) are fairly conserved in their positions, some of them showing different interactions in the four chains due to the intermolecular contacts between the dimers.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1602483 TI - X-ray solution scattering reveals conformational changes upon iron uptake in lactoferrin, serum and ovo-transferrins. AB - X-ray solution scattering has been used for studying the structural changes that take place upon uptake and release of iron from serum and chicken ovo-transferrin and human lactoferrin. In the case of chicken ovo-transferrin, data have been obtained for both the intact protein and the isolated N and C-lobes with and without iron. These studies reveal that both lobes undergo a change that is consistent with an opening of the inter-domain cleft when iron is removed from the protein. We suggest that the conformational change of the protein increases the specificity of receptor binding and that the closed configuration of the iron loaded protein is one, or perhaps the, decisive step in the mechanism for receptor-mediated endocytosis. PMID- 1602484 TI - Solution structure of the fibrin binding finger domain of tissue-type plasminogen activator determined by 1H nuclear magnetic resonance. AB - The amino acid sequence of the first domain of tissue-type plasminogen activator (t-PA) includes eight residues that are highly conserved in the type 1 finger domains found in human fibronectin. A construct comprising 50 residues from this finger domain of t-PA has been expressed and its solution structure has been determined by two-dimensional nuclear magnetic resonance spectroscopy. A total of 782 experimental restraints consisting of 723 interproton distances derived from nuclear Overhauser effect measurements, 43 torsion angles, and 16 hydrogen bond restraints were used as the input for dynamical simulated annealing structure calculations. Twenty-eight structures were obtained that satisfied the experimental data with no single distance violation greater than 0.3 A. The average atomic root-mean-square distribution for the backbone atoms of the final structures was 0.41 (+/- 0.13) A for the well defined part of the structure (residues 4 to 47). The overall fold of the t-PA finger domain shows a striking similarity to that of the seventh type 1 repeat of human fibronectin with the side-chains of conserved residues lying in similar conformations. One significant difference between the two molecules is that hydrophobic residues cover the exposed surface of the principal beta-sheet region in the t-PA finger domain. It is suggested that one face of this region may interact with parts of the complete t-PA protein. PMID- 1602485 TI - Energetics of the strand separation transition in superhelical DNA. AB - In this paper the values of three free energy parameters governing the superhelical strand separation transition are determined by analysis of available experimental data. These are the free energy, a, needed to initiate a run of separation, the torsional stiffness, C, associated with interstrand winding of the two single strands comprising a separated site and the coefficient, K, of the quadratic free energy associated to residual linking. The experimental data used in this analysis are the locations and relative amounts of strand separation occurring in the pBR322 DNA molecule and the measured residual linking, both evaluated over a range of negative linking differences. The analytic method used treats strand separation as a heteropolymeric, co-operative, two-state transition to a torsionally deformable alternative conformation, which takes place in a circular DNA molecule constrained by the constancy of its linking number. The values determined for these parameters under the experimental conditions (T = 310 K, pH = 7.0, monovalent cation concentration = 0.01 M) are a = 10.84(+/- 0.2) kcal/mol, C = 2.5(+/- 0.3) x 10(-13) erg/rad2 and K = 2350(+/- 80) RT/N, where N is the molecular length in base-pairs. In order to assess the accuracy of the author's theoretical methods, these free energy parameters are incorporated into the analysis of superhelical strand separation in different molecules and under other conditions than those used in their evaluation. First, the temperature dependence of transition is treated, then superhelical strand separation is analyzed in a series of DNA molecules having systematic sequence modifications, and the results of these theoretical analyses are compared with those from experiments. In all molecules, transition is predicted in the range of linking differences where it is seen experimentally. Moreover, it occurs at the specific sequence locations that the analysis predicts, and with approximately the predicted relative amounts of transition at each location. The known sensitivities of this transition to changes of temperature and to small sequence modifications are predicted in a quantitatively precise manner by the theoretical results. The demonstrated high-level precision of these theoretical methods provides a tool for the screening of DNA sequences for sites susceptible to superhelical strand separation, some of which may have regulatory or other biological significance. PMID- 1602486 TI - Docking by least-squares fitting of molecular surface patterns. AB - Molecular surfaces are fitted to each other by a new solution to the problem of docking a ligand into the active site of a protein molecule. The procedure constructs patterns of points on the surfaces and superimposes them upon each other using a least-squares best-fit algorithm. This brings the surfaces into contact and provides a direct measure of their local complementarity. The search over the ligand surface produces a large number of dockings, of which a small fraction having the best complementarity and the least steric hindrance are evaluated for electrostatic interaction energy. When applied to molecules taken from crystallographically observed complexes, this procedure consistently assigns the lowest electrostatic energies to correct dockings. On independently determined structures, the ability of the method to discern correct dockings depends on how much conformational difference there is between the free and complexed forms of the molecules. The procedure is found to be fast enough on contemporary workstation computers to permit many conformations to be considered, and tolerant enough to make rather coarse bond dihedral sampling a practicable way to overcome the problem of structural flexibility. PMID- 1602487 TI - Identification of a protein-binding surface by differential amide hydrogen exchange measurements. Application to Bowman-Birk serine-protease inhibitor. AB - The binding surface of soybean trypsin/chymotrypsin Bowman-Birk inhibitor in contact with alpha-chymotrypsin has been identified by measurement of the change in amide hydrogen-exchange rates between free and chymotrypsin-bound inhibitor. Exchange measurements were made for the enzyme-bound form of the inhibitor at pH 7.3, 25 degrees C using fast-flow affinity chromatography and direct measurement of exchange rates in the protein complex from one-dimensional and two-dimensional nuclear magnetic resonance spectra. The interface is characterized by a broad surface of contact involving residues 39 through 48 of the anti-chymotryptic domain beta-hairpin as well as residues 32, 33 and 37 in the anti-chymotryptic domain loop of the inhibitor. A number of residues in the anti-tryptic domain of the protein also have an altered exchange rate, suggesting that there are changes in the protein conformation upon binding to chymotrypsin. These changes in amide exchange behavior are discussed in light of a model of the complex based on the X ray crystallographic structure of turkey ovomucoid inhibitor third domain bound to a alpha-chymotrypsin, and the structure of free Bowman-Birk inhibitor determined in solution by two-dimensional nuclear magnetic resonance spectroscopy. The chymotrypsin-binding loop of Bowman-Birk inhibitor in the model is remarkably similar to the binding loop conformation in crystal structures of enzyme-bound polypeptide chymotrypsin inhibitor-I from potatoes, turkey ovomucoid inhibitor third domain, and chymotrypsin inhibitor-II from barley seeds. PMID- 1602488 TI - Mutation of asparagine 111 of rubisco from Rhodospirillum rubrum alters the carboxylase/oxygenase specificity. AB - The conserved asparagine 111 of ribulose-1,5-bisphosphate carboxylase/oxygenase from the photosynthetic bacteria Rhodospirillum rubrum was identified as a candidate for a side-chain that might be involved in the carboxylase/oxygenase specificity. It was replaced by site-directed mutagenesis with aspartic acid, leucine, glutamine or glycine residues. The mutant enzymes exhibit a very low carboxylase activity compared with the wild-type enzyme. The values of Km(RuBP) and kcat for Asn111----Gly, the most active mutant, are 420 microM and 0.034 s-1, compared with 13 microM and 3.0 s-1 for wild-type. The mutation of Asn111----Gly causes a more than tenfold decrease in the CO2/O2 specificity factor, tau, tau Asn111----Gly = 0.56 and tau wild-type = 6.7. This is the first reported change in rubisco specificity by a single site-directed mutation alone and suggests a target for future protein engineering studies. PMID- 1602489 TI - Binding of the yeast tRNA(Met) anticodon by the cognate methionyl-tRNA synthetase involves at least two independent peptide regions. AB - As for Escherichia coli methionine tRNAs, the anticodon triplet of yeast tRNA(Met) plays an important role in the recognition by the yeast methionyl-tRNA synthetase (MetRS), indicating that this determinant for methionine identity is conserved in yeast. Efficient aminoacylation of the E. coli tRNA(Met) transcript by the heterologous yeast methionine enzyme also suggests conservation of the protein determinants that interact with the CAU anticodon sequence. We have analysed by site-directed mutagenesis the peptide region 655 to 663 of the yeast MetRS that is equivalent to the anticodon binding region of the E. coli methionine enzyme. Only one change, converting Leu658 into Ala significantly reduced tRNA aminoacylation. Semi-conservative substitutions of L658 allow a correlation to be drawn between side-chain volume of the hydrophobic residue at this site and activity. The analysis of the L658A mutant shows that Km is mainly affected. This suggests that the peptide region 655 to 663 contributes partially to the binding of the anticodon, since separate mutational analysis of the anticodon bases shows that kcat is the most critical parameter in the recognition of tRNA(Met) by the yeast synthetase. We have analysed the role of peptide region (583-GNLVNR-588) that is spatially close to the region 655 to 663. Replacements of residues N584 and R588 reduces significantly the kcat of aminoacylation. The peptide region 583-GNLVNR-588 is highly conserved in all MetRS so far sequenced. We therefore propose that the hydrogen donor/acceptor amino acid residues within this region are the most critical protein determinants for the positive selection of the methionine tRNAs. PMID- 1602490 TI - Crystallization and preliminary diffraction studies of hydroxypyruvate reductase (D-glycerate dehydrogenase) from Hyphomicrobium methylovorum. AB - Two crystal forms of hydroxypyruvate reductase (D-glycerate dehydrogenase) from the methylotrophic bacterium Hyphomicrobium methylovorum have been grown from ammonium sulphate solutions. One crystal form is triclinic, with unit cell parameters a = 60.4 A, b = 60.5 A, c = 66.3 A, alpha = 102.3 degrees, beta = 113.7 degrees and gamma = 102.7 degrees, suggesting that a dimer (monomer M(r) 38,000) occupies the unit cell. This crystal form diffracts to beyond 2.4 A resolution and is suitable for crystallographic structure analysis. PMID- 1602491 TI - Preliminary crystallographic analysis of murine macrophage inflammatory protein 2. AB - Macrophage inflammatory protein 2 (MIP-2) has been crystallized by vapor diffusion of an 11 mg/ml protein solution in 100 mM-ammonium acetate against 30 to 40% polyethylene glycol (average molecular mass of 3350 Da). The crystals belong to space group P2(1)2(1)2(1) and have unit cell dimensions of a = 42.7 A, b = 59.3 A, and c = 100.3 A. The molecular mass of the protein and volume of the unit cell suggest that there are four monomers in the asymmetric unit. A data set to 2.3 A has been collected, and the self-rotation function identifies the presence of a non-crystallographic 2-fold axis. PMID- 1602492 TI - A phylogenetic analysis based on the gene encoding phosphoglycerate kinase. AB - We have determined the nucleotide sequence of both genomic and complementary DNA (cDNA) for the gene encoding the glycolytic enzyme phosphoglycerate kinase from the ciliated protozoan Tetrahymena thermophila. The amino acid sequence for the enzyme has also been derived from the cDNA sequence. The gene contains an open reading frame of 1260 nucleotides encoding 420 amino acids. Coding sequence in genomic DNA is interrupted by two introns at positions corresponding to introns 3 and 4 in mammalian phosphoglycerate kinase genes. The derived amino acid sequence was used to prepare a phylogeny by aligning the Tetrahymena sequence with 25 other phosphoglycerate kinase amino acid sequences. The Tetrahymena sequence is a typical eukaryotic sequence. There is recognizable and clear homology across species that cover nearly the complete range of life forms. The phylogenetic reconstruction of these sequences generally supports the conclusions that have been reached using rRNA sequences. PMID- 1602493 TI - Early evolutionary relationships among known life forms inferred from elongation factor EF-2/EF-G sequences: phylogenetic coherence and structure of the archaeal domain. AB - Phylogenies were inferred from both the gene and the protein sequences of the translational elongation factor termed EF-2 (for Archaea and Eukarya) and EF-G (for Bacteria). All treeing methods used (distance-matrix, maximum likelihood, and parsimony), including evolutionary parsimony, support the archaeal tree and disprove the "eocyte tree" (i.e., the polyphyly and paraphyly of the Archaea). Distance-matrix trees derived from both the amino acid and the DNA sequence alignments (first and second codon positions) showed the Archaea to be a monophyletic-holophyletic grouping whose deepest bifurcation divides a Sulfolobus branch from a branch comprising Methanococcus, Halobacterium, and Thermoplasma. Bootstrapped distance-matrix treeing confirmed the monophyly-holophyly of Archaea in 100% of the samples and supported the bifurcation of Archaea into a Sulfolobus branch and a methanogen-halophile branch in 97% of the samples. Similar phylogenies were inferred by maximum likelihood and by maximum (protein and DNA) parsimony. DNA parsimony trees essentially identical to those inferred from first and second codon positions were derived from alternative DNA data sets comprising either the first or the second position of each codon. Bootstrapped DNA parsimony supported the monophyly-holophyly of Archaea in 100% of the bootstrap samples and confirmed the division of Archaea into a Sulfolobus branch and a methanogen halophile branch in 93% of the bootstrap samples. Distance-matrix and maximum likelihood treeing under the constraint that branch lengths must be consistent with a molecular clock placed the root of the universal tree between the Bacteria and the bifurcation of Archaea and Eukarya. The results support the division of Archaea into the kingdoms Crenarchaeota (corresponding to the Sulfolobus branch and Euryarchaeota). This division was not confirmed by evolutionary parsimony, which identified Halobacterium rather than Sulfolobus as the deepest offspring within the Archaea. PMID- 1602497 TI - On healing. PMID- 1602494 TI - Insect muscle actins differ distinctly from invertebrate and vertebrate cytoplasmic actins. AB - Invertebrate actins resemble vertebrate cytoplasmic actins, and the distinction between muscle and cytoplasmic actins in invertebrates is not well established as for vertebrate actins. However, Bombyx and Drosophila have actin genes specifically expressed in muscles. To investigate if the distinction between muscle and cytoplasmic actins evidenced by gene expression analysis is related to the sequence of corresponding genes, we compare the sequences of actin genes of these two insect species and of other Metazoa. We find that insect muscle actins form a family of related proteins characterized by about 10 muscle-specific amino acids. Insect muscle actins have clearly diverged from cytoplasmic actins and form a monophyletic group emerging from a cluster of closely related proteins including insect and vertebrate cytoplasmic actins and actins of mollusc, cestode, and nematode. We propose that muscle-specific actin genes have appeared independently at least twice during the evolution of animals: insect muscle actin genes have emerged from an ancestral cytoplasmic actin gene within the arthropod phylum, whereas vertebrate muscle actin genes evolved within the chordate lineage as previously described. PMID- 1602496 TI - On the evolution of the bacterial major sigma factors. AB - The existence of internal sequence homologies between the N-terminal halves of the gram-negative bacterial major sigma factors and their C-terminal halves, which correspond to minor factors, is reported. In the case of Escherichia Salmonella sigma-70, an apparent homology was even found between the C-terminal helix-turn-helix DNA-binding motif and the corresponding region of the peptide N half, which, however, is not directly engaged in promoter recognition. It is proposed that major sigma factors may have originated by duplication and fusion of a DNA unit related to the ancestral gene for the whole sigma family. Coevolution of major sigma structures and complex promoters is suggested. PMID- 1602498 TI - Health insurance legislative update. PMID- 1602495 TI - Evolution of EF-hand calcium-modulated proteins. II. Domains of several subfamilies have diverse evolutionary histories. AB - In the first report in this series we described the relationships and evolution of 152 individual proteins of the EF-hand subfamilies. Here we add 66 additional proteins and define eight (CDC, TPNV, CLNB, LPS, DGK, 1F8, VIS, TCBP) new subfamilies and seven (CAL, SQUD, CDPK, EFH5, TPP, LAV, CRGP) new unique proteins, which we assume represent new subfamilies. The main focus of this study is the classification of individual EF-hand domains. Five subfamilies- calmodulin, troponin C, essential light chain, regulatory light chain, CDC31/caltractin--and three uniques--call, squidulin, and calcium-dependent protein kinase--are congruent in that all evolved from a common four-domain precursor. In contrast calpain and sarcoplasmic calcium-binding protein (SARC) each evolved from its own one-domain precursor. The remaining 19 subfamilies and uniques appear to have evolved by translocation and splicing of genes encoding the EF-hand domains that were precursors to the congruent eight and to calpain and to SARC. The rates of evolution of the EF-hand domains are slower following formation of the subfamilies and establishment of their functions. Subfamilies are not readily classified by patterns of calcium coordination, interdomain linker stability, and glycine and proline distribution. There are many homoplasies indicating that similar variants of the EF-hand evolved by independent pathways. PMID- 1602499 TI - Studies on lead exposure in patients of a neighborhood health center: Part II. A comparison of women of childbearing age and children. AB - The second part of this study deals with blood lead (PbB) levels in 541 pregnant women and 351 nonpregnant women of childbearing age residing in the health center's catchment area. Each blood sample was analyzed for erythroprotoporphyrin (EP) and PbB. Comparisons of these data were made with national data on women of childbearing age and with children in our catchment area, as well as with children nationally. Mean PbB and prevalence rates at greater than or equal to 10 and greater than or equal to 15 micrograms/dL were higher in the nonpregnant women of the catchment area than in the pregnant women. For comparison with women nationally, the data on these two groups were combined because national data did not clearly distinguish between pregnant and nonpregnant women. The women in the catchment area showed mean PbB and prevalence rates at the two ranges noted above that were not only higher than in white women but also generally higher than in black women nationally. Thus, this rank order was similar to that reported earlier for children. The comparisons between women and children living in the same environment showed that the children have significantly higher mean PbBs and prevalence rates at the two ranges than the women. The physiological and environmental bases for these differences are discussed. As in the study on children, the EP is also not adequate as a screening procedure for identifying women with PbB levels greater than or equal to 25 and greater than or equal to 15 micrograms/dL. PMID- 1602500 TI - Black health professional families: assessment of strengths and stability. AB - Despite pernicious racism, most black health professionals achieve professional success and most have stable marriages. A 19-item questionnaire was designed to assess this hypothesis following a lecture on the strengths and weaknesses of black health professional families to physicians, dentists, and their spouses (n = 38) at the 1990 annual meeting of the combined Old North State Medical and Dental Societies of North Carolina. Surprisingly, these families seemed eager to disclose feelings about themselves, their professions, and their marriages. Major preliminary findings were that these health professionals were more prone to indicate unhappiness than their spouses and less likely to see racism as an impediment to careers, and more willing to acknowledge that they would like to correct something in their lives. PMID- 1602501 TI - Patterns of coal workers' pneumoconiosis in Appalachian former coal miners. AB - To aid in diagnostic chest film interpretation of coal workers' pneumoconiosis, a composite profile of common radiologic patterns was developed in 98 Appalachian former coal miners who were diagnosed as having coal miner's pneumoconiosis and who applied for black lung benefits. The mean age was 61 years, with a lifetime coal mine dust exposure of 18.7 years. Results showed that chest radiographs of coal workers' simple pneumoconiosis contained small irregular linear opacities more frequently (47%) than small rounded opacities. Sparse profusion of all small opacities was the rule. Small opacities involved two out of six lung zones simultaneously 39% of the time while other combinations occurred less frequently. Lower zones were involved more frequently than upper ones. Thickened pleura occurred in 18% of radiographs. Other frequent radiographic abnormalities were parenchymal calcifications (19%), marked emphysema (12%), and inactive tuberculosis (12%). Calcification of the aortic knob, a degenerative process reflecting age, occurred in 9%. Only one instance of complicated coal workers' pneumoconiosis (progressive massive fibrosis) was encountered (0.7%). Many of the descriptive features of coal workers' pneumoconiosis noted in the literature were not observed in this study. Only one instance of complicated pneumoconiosis was encountered. PMID- 1602502 TI - Do African-American men and women differ in their knowledge about AIDS, attitudes about condoms, and sexual behaviors? AB - This study identified a sample of young African-American men and women classified as having multiple sex partners or one sex partner. Of the 149 men, 71 (47%) were classified as having multiple sex partners and 78 (53%) as having one sex partner. Of the 165 women, 29 (19%) were classified as having multiple sex partners and 126 (81%) as having one sex partner. Results indicated that the groups did not differ in their knowledge about acquired immunodeficiency syndrome (AIDS). However, attitudes about condom use differed significantly by gender (P less than .01) and by multiple sex status (P less than .001). Angry reactions regarding the negotiation of condom use occurred more with men than with women (P less than .05). Men and members of the multiple sex partners group tended to engage in more risky sexual behavior. These two groups also had a significantly (P less than .001) higher incidence of gonorrhea. While the multiple sex partners group had significantly more smokers (P less than .01), drinkers (P less than .01), and crack users (P less than .05), men were significantly higher consumers of marijuana (P less than .001) and alcohol (P less than .01). Overall, the results indicate that African Americans are knowledgeable about AIDS, but there appears to be a gap between knowledge and risky sexual behaviors. Prospective studies are needed to clarify the factors that determine the relationship (or lack of) between knowledge and risky sexual behaviors. Without such studies, a major part of the foundation that is needed for the development of sensitive and effective AIDS prevention programs for African Americans will be missing. PMID- 1602503 TI - The pattern of isolated sleep paralysis among Nigerian nursing students. AB - In a cross-sectional study of the pattern of isolated sleep paralysis among the entire population of nursing students at the Neuropsychiatric Hospital in Abeokuta, Nigeria (consisting of 58 males and 37 females), 44% admitted having experienced this phenomenon. The findings largely supported the results of a similar study of Nigerian medical students, except that there was a slight male preponderance among those who had the experience. Visual hallucination was the most common perceptual problem associated with the episodes, and all the affected subjects were most distressed by the experience. Whereas sleep paralysis in this country has not been found to be significantly associated with psychosocial distress or differences in personality profile, the popular view in Africa and the United States is that it is caused by witchcraft. PMID- 1602504 TI - Treatment of urinary infections in pregnancy using single versus 10-day dosing. AB - Pregnant patients with symptomatic and asymptomatic urinary tract infections were treated with a long and a short antibiotic regimen. Two hundred two patients were randomized prospectively to a single oral dose of 3.5 g ampicillin plus 1 g probenecid (98 patients) versus 500 mg ampicillin orally four times a day for 10 days (104 patients). The multiple-dose cure rate was statistically significantly better than that of the single-dose regimen (67.3% versus 57.1%, respectively). Interestingly, for resistant organisms, the cure rate for the long and short regimens was similar (48% versus 43%, respectively). In vitro susceptibility testing does not appear to be a good predictor of cure, at least for the single dose group. Single-dose therapy with ampicillin and probenecid does not provide an optimal cure rate or prevent reinfection during pregnancy. Possible reasons for these findings are discussed. PMID- 1602505 TI - Clinical apnea as an early manifestation of Pneumocystis carinii pneumonia in an infant with perinatal HIV-1 infection. AB - This article describes the first case of Pneumocystis carinii pneumonia in a human immunodeficiency virus (HIV) seropositive infant in whom apnea was the earliest presenting clinical finding. Pediatricians treating infants with HIV infection need to be aware of this unusual clinical presentation of P carinii pneumonia to avoid a delay in diagnosis and management of this disease. PMID- 1602506 TI - Neonatal bone infarction following cord sepsis: case report. AB - An unusual case of infarction of the tibia in a neonate who presented with sepsis following poor cord management at birth is reported. He was managed as for necrotizing enterocolitis and had limited debridement of infarcted limb because the parents refused amputation of the limb. This patient was a diagnostic problem. Necrotizing fasciitis and in retrospect purpura fulminans are considered as possible diagnoses and are discussed briefly. PMID- 1602507 TI - Patient dumping--new style. PMID- 1602508 TI - Black dentistry in the 21st century. PMID- 1602509 TI - AIDS and racism in America. AB - Institutionalized racism affects general health care as well as acquired immunodeficiency syndrome (AIDS) health intervention and services in minority communities. The overrepresentation of minorities in various disease categories, including AIDS, is partially related to racism. The national response to the AIDS epidemic in minority communities has been slow, showing an insensitivity to ethnic diversity in prevention efforts and AIDS health services. PMID- 1602510 TI - A prospective study of insulin-dependent diabetic Nigerian Africans. AB - Newly diagnosed insulin-dependent diabetic Nigerian Africans were studied prospectively over a 6-year period and were analyzed for sex, age at diagnosis, and month of onset of symptoms. Insulin-dependent diabetes mellitus (IDDM) rarely occurred in patients younger than the age of 10. A female preponderance occurred in those aged 20 and younger, and a male preponderance occurred in those aged 20 and older. The onset of symptoms occurred predominantly in the dry months of the year (October to March), peaking in February. The educational level and current employment status of the patients were compared with age- and sex-matched controls. The diabetics were found to have significantly less education, and approximately one third (34.9%) were unemployed compared with 10% of the controls. Control of the disease was found to be poor in three fourths of the patients. Various factors that prevent young diabetics in developing countries from living a full life are discussed. PMID- 1602511 TI - Primary tumors of the liver. AB - Primary tumors of the liver that are of clinical significance are rare. Ninety five percent of such lesions when encountered will be malignant and only 5% will be benign. Malignant primary hepatic lesions represent 2% to 3% of primary cancers encountered in the United States. Hepatocellular carcinoma constitutes 90% of malignant liver primaries in the adult. Seventy-five percent of cases are associated with cirrhosis of the liver and patients with hepatitis B infection have a 33- to 200-fold excess risk for this malignancy. Cholangiocarcinoma represents 5% to 10% of hepatic primary malignancies while hepatoblastoma is distinctly uncommon in adults. Treatment is primarily surgical, and resectability is limited by the presence of cirrhosis and spread of the tumor within and outside of the liver. Of the benign liver tumors, the liver cell adenoma seem to be associated with oral contraception and have a proclivity for intraperitoneal hemorrhage, especially during pregnancy. Focal nodular hyperplasia is a tumor like condition that also may be associated with oral contraception. This article describes five cases, two of which had quite unique presentations. PMID- 1602512 TI - Stereotactic external beam irradiation system. AB - Stereotactic localization is of vital importance in treating small intracranial lesions either with interstitial or external beam irradiation. This article describes a simple, fast, accurate, and verifiable system that can be used with a standard computerized axial tomography (CAT) scanner and linear accelerator for stereotactic external beam irradiation. PMID- 1602513 TI - The role of surgery in treating pleuropulmonary suppurative disease--review of 77 cases managed at Queens Hospital Center between 1986 and 1989. AB - Despite the generally salutary experience in recent years of managing suppurative pleuropulmonary disease, empyemas and lung abscesses have persisted and increased in incidence in hospitals such as Queens Hospital Center that serve large numbers of the socioeconomically disadvantaged. This study documents the etiology, clinical presentation, treatment, and treatment results of suppurative pleuropulmonary disease at Queens Hospital Center, which serves a large segment of the urban poor, many of whom are black. Results indicate that contributory or antecedent etiologic factors include a history of prior disease (specifically pneumonia, lung abscess, obstructive lung disease, pulmonary neoplasia, and tuberculosis); a predisposition to constitutional or immunologic deficiencies (specifically, alcoholism, anemia/malnutrition, drug abuse, and acquired immunodeficiency syndrome [AIDS]); conditions contributing to tracheobronchial aspiration (specifically, alcoholism and seizure disorders); and a miscellaneous group such as prior surgery, cardiovascular disease, and sepsis syndrome. The patients in this study were young with maximal incidence occurring in the third to fifth decades of life. Patients were predominantly male (75%) and black (66%). There were 18 deaths (23%), with sepsis being the cause in 10 (56%). Most surgical interventions were conservative, ie, bronchoscopies (48), thoracenteses (43), and tube thoracotomies (39). Thirty-one open thoracotomies were performed for drainage, decortication, or pulmonary resection. The surgical mortality was three cases or 5% of the patients who underwent surgery. The designated incidence of proven AIDS in this series (29%) was low, undoubtedly because many patients refused testing, and the multiple gram-positive and gram-negative infections that were seen did not conform to the Centers for Disease Control criteria for diagnosis and case reporting for AIDS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602514 TI - The endocrinology and pathophysiology of alcoholic cirrhosis and functional renal failure--a review. AB - The pathophysiology and characteristics of decompensated alcoholic cirrhosis and functional renal failure are reviewed. The review will be restricted to alcoholic cirrhosis, because most cases of functional renal failure in the United States occur in the setting of alcoholic cirrhosis, which is also the most common cause of ascites in North America and Europe. Moreover, hepatorenal syndrome may complicate other forms of liver disease besides alcoholic cirrhosis, but the pathogenesis in such circumstances may not be the same as in the cirrhotic state. PMID- 1602515 TI - Common emergencies in cancer medicine: hematologic and gastrointestinal syndromes. AB - A myriad of both primary and secondary hematologic and gastrointestinal system related clinical problems may exist in the cancer patient. This review outlines a standard approach to the prompt diagnosis and therapeutic intervention for these clinical issues. PMID- 1602516 TI - The injured duodenum. AB - Duodenal injuries are relatively infrequent. A high index of suspicion is required because the retroperitoneal location of the duodenum makes the diagnosis of injuries difficult. Physical findings may be subtle and nonspecific. Contrast studies are often required to make the diagnosis. Options for operative management are outlined. Morbidity and mortality are related to associated injuries and delay in diagnosis. PMID- 1602517 TI - The operative approach to pancreatic injury. AB - Major pancreatic trauma is uncommon and often challenging even for the most experienced trauma surgeon. An organized, well-rehearsed operative approach to these injuries represents the surgeon's best defense. This article highlights operative decision-making. Operative assessment is reliable. The integrity of the main pancreatic duct is the major discriminating variable in the management of pancreatic injury. Pancreaticoduodenectomy can be done safely for devitalizing injuries to the head of the pancreas associated with major duodenal and common bile duct injury. For selected cases, distal pancreatectomy with splenic preservation is realistic. The surgeon must have a wide array of procedures from which to select for major complicated pancreatic trauma. PMID- 1602518 TI - Isolated ascending colon ulceration in a patient with chronic renal insufficiency. AB - Chronic renal hemodialysis or transplantation may be accompanied by a myriad of gastrointestinal problems. Ischemic bowel disease, spontaneous perforation diverticulitis, appendicitis, fistulae, and angiodysplasia have all been reported in the literature. Isolated colonic ulcerations have been described as a cause of both massive hemorrhage and spontaneous perforation. The exact predisposing factors are unknown. Ischemia, immunosuppression, and cytomegalovirus may play important roles in pathogenesis. This article describes a case of both hemorrhage and spontaneous colonic perforation accompanying end-stage renal disease in a patient who was not undergoing long-term dialysis or posttransplantation immunosuppression. PMID- 1602519 TI - An American health dilemma: a history of blacks in the health system. AB - The present black health crisis is a continuum. After 346 years of neglect, flawed efforts were made to admit black Americans to the "mainstream" health system. Gains were significant from 1965 to 1975; however, since then black health status has eroded. Since colonial times, the racial dilemma that affected America's liberal democratic system also distorted medical relationships and institutions. There are clear connections between campaigns to defeat bills that would improve the health of blacks and other disadvantaged groups and acquiescence with the present reassignment of them to the underfunded, overcrowded, inferior, public health-care sector. Physician leadership helped to establish the slaveocracy, create the racial inferiority myths, and build the segregated health subsystem for blacks and the poor. Clearly, if the history based health disparities are to be resolved, black physician leadership will be necessary. Without justice and equity in health care, the dream of Martin Luther King will never become a reality for African Americans. PMID- 1602520 TI - Dietary modification of drug-metabolizing enzyme activities: dose-response effect of flavonoids. AB - The induction of drug-metabolizing enzymes for different dietary flavonoids has been shown previously. The purpose of this study was to determine the threshold effect of these components. Rats were fed diets containing flavone, flavanone, or tangeretin at different levels (20, 50, 200, 500, and 200 ppm). Flavone induced ethoxyresorufin and pentoxyresorufin dealkylase activities at 500 ppm and arylhydrocarbon hydroxylase at 200 ppm. Epoxide hydrolase and glutathion transferase were increased at 200 ppm. UDP-glucuronyl transferases were enhanced at 20 ppm. Flavanone induced pentoxyresorufin dealkylase and arylhydrocarbon hydroxylase at the greatest level. In contrast, epoxide hydrolase and conjugating enzymes were increased at the lowest dose. Significant induction was seen only for ethoxyresorufin deethylase and UDP-glucuronyl transferase with diets containing 2000 ppm tangeretin. We conclude that the threshold effect depends on the chemical structure of the flavonoid and the enzyme activity. Low threshold doses for conjugating enzymes may be important for the anticarcinogenicity properties of these compounds. PMID- 1602521 TI - Metabolism and disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring-necked pheasant hens, chicks, and eggs. AB - The T 1/2 for whole-body elimination of [3H]-2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) derived radioactivity in ring-necked pheasant hatchlings was 13 d, whereas in adult hen pheasants that were not producing eggs it was 378 d. All TCDD derived radioactivity in hen tissues was from the parent compound. The oral bioavailability of TCDD in the adult hen pheasant varied with the environmental matrix, with 30% of the dose absorbed from a suspension of earthworms, 33% absorbed from a soil suspension, 41% absorbed from a suspension of paper mill sludge, and 58% absorbed from a suspension of crickets. A cumulative dose of 1.0 micrograms TCDD/kg body weight, administered as weekly doses of 0.1 micrograms/kg for 10 wk, did not adversely affect hen condition or egg production. Under these exposure conditions, hens translocated about 1% of their cumulative TCDD dose to each of the first 15 eggs laid. All of the TCDD-derived radioactivity in the eggs was the parent compound and was confined entirely to the yolk; no TCDD was detected in egg albumin. We conclude that TCDD was more persistent in pheasant hens than in chicks and that egg laying was an important route of elimination in the hen. PMID- 1602522 TI - Airway hyperresponsiveness in guinea pigs exposed to acid-coated ultrafine particles. AB - Although several epidemiological studies have provided evidence that airborne sulfate particles can produce adverse health effects in susceptible individuals, there is only limited data demonstrating respiratory effects in human volunteers and experimental animals at near ambient concentrations. We have demonstrated previously that the mixing of metal oxide particles with SO2 under humid conditions produces acid-coated particles that are significantly more potent in causing pulmonary function changes than pure acid droplets. The present study examined the nonspecific airway responsiveness to acetylcholine in guinea pigs exposed to acid-coated zinc oxide particles. One and a half hours after a 1-h exposure to the aerosols or a control atmosphere, pulmonary resistance (RL) was measured in awake, spontaneously breathing animals before and during a challenge with increasing doses of iv acetylcholine (Ach). The provocative infusion rate of Ach that resulted in a 100% increase in RL (PR100) was significantly decreased (p less than .05) in animals exposed to sulfuric acid-coated metal oxide particles (approximately 30 micrograms/m3 sulfate) compared to control animals exposed to furnace gases (79.6 +/- 19.4 vs. 179.6 +/- 16.2 micrograms/kg/min, mean +/- SE, respectively). The PR100 of animals exposed to SO2 (109.1 +/- 45.4) or metal oxide particles (106.7 +/- 38.1) alone was not significantly different from that of furnace gas control animals, indicating that the acid coating on the metal oxide particles and not the particles themselves or the SO2 was responsible for the decrease in the PR100. Moreover, a 10-fold greater amount of total sulfate as a pure aqueous sulfuric acid aerosol was necessary to produce a decrease in PR100 (88.6 +/- 11.0 micrograms/kg/min) equivalent to that produced by coated particles. These results suggest that acute exposure to near-ambient concentrations of sulfuric acid under conditions that promote the formation of acid as a surface coating in respirable particles can induce a nonspecific airway hyperresponsiveness. In a similar manner, a dose-dependent significant decrease in PR100 was also produced in animals exposed to sodium sulfite droplets. Thus a single exposure to different forms of sulfur oxide aerosols can induce an alteration in the responsiveness of airway smooth muscle in the guinea pig. PMID- 1602523 TI - Toxicity and reproductive effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin in ring necked pheasant hens. AB - Hen pheasants (Phasianus colchicus) injected with graded single doses of TCDD (6.25, 25, or 100 micrograms/kg) exhibited delayed-onset body weight loss and mortality--classic signs of the wasting syndrome. The lowest single dose of TCDD to produce this effect was 25 micrograms/kg. When hen pheasants were treated weekly with far lower doses of TCDD (0.01-1.0 microgram/kg/wk) for 10 wk, signs of the wasting syndrome and mortality were also produced. The lowest cumulative TCDD dose required to produce the response, using a weekly dosing regimen, was 10 micrograms/kg. Furthermore, using this dosing regimen, egg production by hens treated with a cumulative TCDD dose of 10 micrograms/kg was reduced, as was hatchability of their eggs. We conclude that hen pheasants are responsive to the overt toxic effects of TCDD and that the lowest cumulative dose of TCDD that produces overt signs of toxicity, 10 micrograms/kg, also reduces egg production and egg hatchability. PMID- 1602524 TI - Crossing disciplinary boundaries. PMID- 1602525 TI - Changes in force production, blood lactate and EMG activity in the 400-m sprint. AB - The neural activation (iEMG) and selected stride characteristics of six male sprinters were studied for 100-, 200-, 300- and 400-m experimental sprints, which were run according to the velocity in the 400 m. Blood lactate (BLa) was analysed and drop jumps were performed with EMG registration at rest and after each sprint. Running velocity (P less than 0.001) and stride length (P less than 0.05) decreased and contact time increased (P less than 0.01) during the 400-m sprint. The increase in contact time was greatest immediately after runs of 100 and 300 m. The peak BLa increased and the rate of BLa accumulation decreased with running distance (P less than 0.001). The height of rise of the centre of mass in the drop jumps was smaller immediately after the 300 m (P less than 0.05) and the 400 m (P less than 0.01) than at rest, and it correlated negatively with peak BLa (r = -0.77, P less than 0.001). The EMG and EMG:running velocity ratio increased with running distance. It was concluded that force generation of the leg muscles had already begun to decrease during the first quarter of the 400-m sprint. The deteriorating force production was compensated for until about 200-300 m. Thereafter, it was impossible to compensate for fatigue and the speed of running dropped. According to this study, fatigue in the 400-m sprint among trained athletes is mainly due to processes within skeletal muscle rather than the central nervous system. PMID- 1602526 TI - A test for the measurement of pulmonary diffusion capacity during high-intensity exercise. AB - The most commonly used technique for the measurement of pulmonary diffusing capacity (DL) is the single-breath hold technique requiring a 10-s breath-hold after the maximal inspiration of carbon monoxide (0.3% CO) and helium (10% He). To measure pulmonary diffusing capacity in our experiments, we had the added advantage of the use of the Gould Pulmonary Function Laboratory that automates the collection and recording of data and the calibration of equipment for each test. However, this technique, DL(CO), is difficult to use during exercise of moderate or elevated intensity because of the lengthy breath-hold. Thus, the purpose of the present study was to compare DL(CO) with 3-s and 5-s breath-holds to a 10-s breath-hold at rest and during moderate and intense exercise in 14 subjects. As expected, an increase in the DL(CO) was observed during moderate and intense exercise when compared to resting values (45.7 +/- 10.0 and 53.0 +/- 7.6 vs 32.1 +/- 7.7 ml CO min-1 mmHg-1). No difference was observed between values for DL(CO) measured at varying breath-hold times at rest (3 s: 32.9 +/- 7.4; 5 s: 32.0 +/- 7.5; 10 s: 31.4 +/- 8.2 ml CO min-1 mmHg-1) or during moderate exercise (3 s: 45.9 +/- 10.1; 5 s: 45.9 +/- 10.6; 10 s: 45.2 +/- 10.4 ml CO min-1 mmHg-1) or intense exercise (3 s: 52.1 +/- 8.3; 5 s: 54.3 +/- 9.3; 10 s: 52.6 +/- 5.2 ml CO min-1 mmHg-1). Reliability coefficients indicated that the use of a 3-s breath hold was appropriate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602527 TI - Assessment of predispositions for endurance running from field tests. AB - Field tests of speed and endurance may be used to evaluate the probability of success and to create efficient training strategies for sports. Currently, both invasive and non-invasive methods are used for this purpose. While invasive methods cause some discomfort to subjects, non-invasive methods may employ practices associated with the sport itself. One such method employs the linear relationship between exercise intensity or running speed and distance covered running at that speed represented on a semi-logarithmic scale. The separation of endurance runners into three different groups can be confirmed by different values for the slope coefficient (b) of this linear relation. According to findings among top Czechoslovak endurance runners, supplemented by the data of other authors, the values of coefficient b in middle-distance runners are in the range -2.166 to -1.700, in long-distance runners -1.520 to -1.050 and in marathon runners -0.836 to -0.436. Similarly, a separation of young endurance runners into groups of middle-distance and long-distance runners must be within the range 2.158 to -1.800 and for young long-distance runners -1.700 to -1.300. Based on these findings, the optimum competitive distance for adult athletes can be established in relation to current training status. In young athletes, it is possible to select gifted runners with predispositions for middle-distance and long-distance running. For both groups of athletes, more efficient training methods can be selected to optimize their predispositions for maximal performance. PMID- 1602528 TI - Individual differences in visual information processing rate and the prediction of performance differences in team sports: a preliminary investigation. AB - This study used a backward-masking paradigm to examine individual differences in rate of visual information processing among university basketball, ice hockey and Canadian football players. Displays containing four letters were presented for stimulus durations ranging from 25 to 300 ms. Following stimulus offset, a masking stimulus was presented for 200 ms. The subjects were instructed to write down as many letters as possible from the briefly presented stimulus display on a specially prepared response grid. The results indicated consistent individual differences in rate of visual information processing. More importantly, it was found that rate of visual information processing as indexed by the backward masking technique, has promising validity for predicting general performance excellence in university ice hockey and basketball players. Individual differences in rate of visual information processing were interpreted as reflecting the operation of attentional factors. PMID- 1602529 TI - Calculating upper limb inertial parameters. AB - In the kinematic and kinetic analysis of human movement, an accurate assessment of the inertial properties of the body segments under investigation is often essential. Statistical and geometric models of the segments of the upper limb were examined to determine their ability to predict the moments of inertia of these segments. The cadaver data of Chandler et al. (1975) were used as the criteria with which computed values were compared. The regression equations of Hinrichs (1985) gave the most accurate results; the geometric models appeared to offer the greatest flexibility. PMID- 1602530 TI - Analysis of the physical demands of international rugby union. AB - The aim of this study was to investigate the physical demands of international rugby union. Five games in the 1989-90 Five Nations Championship were analysed using video-recordings of live television transmissions. When the ball was in open play, the average running pace of players central to the action ranged from 5 to 8 m s-1. This together with scrum, lineout, ruck and maul was classified as high-intensity exercise. The density of work was measured by timing the work:rest ratios (W:RRs) throughout each game. The mean duration of the work periods was 19 s and the most frequent W:RRs were in the range of 1:1 to 1:1.9. On average, a scrum, lineout, ruck or maul occurred every 33 s. The ball was in play for an average of 29 min during a scheduled time of play of 80 min. To complement the time-motion analysis, blood samples were taken from six players throughout a first-class game. The highest measured blood lactate (BLa) concentrations for each individual ranged from 5.8 to 9.8 mM. Running speed, duration, BLa levels, physical confrontation and, most particularly, the density of work as illustrated by the W:RRs indicate that the game places greater demands on anaerobic glycolysis than previously reported. This has implications for the physical conditioning of rugby union players. PMID- 1602531 TI - Expression and characterization of genetically engineered human immunodeficiency virus-like particles containing modified envelope glycoproteins: implications for development of a cross-protective AIDS vaccine. AB - Noninfectious human immunodeficiency virus type 1 (HIV-1) viruslike particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. We engineered four expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment at two different locations within the conserved region 2 (C2) of gp120, either 173 or 242 residues away from the N terminus of the mature subunit, resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. However, insertion of the V3(MN) loop segment into other regions of gp120 led to the production of envelope-deficient viruslike particles. Immunization with HIV like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1LAI and HIV-1MN isolates. This study, therefore, demonstrates the feasibility of genetically engineering optimized HIV-like particles capable of eliciting cross-neutralizing antibodies. PMID- 1602533 TI - Human immunodeficiency virus type 1 Tat-mediated trans activation correlates with the phosphorylation state of a cellular TAR RNA stem-binding factor. AB - Protein kinase C (PKC) is involved in the mitogenic stimulation of cell proliferation and has recently been reported to be essential for Tat-mediated trans activation. We have determined that RNA binding of a cellular factor which specifically interacts with the trans-activation response region (TAR) is blocked in cells depleted of PKC activity by chronic phorbol myristate acetate stimulation. We also show that nuclear extracts can be depleted of the cellular TAR-binding factor by in vitro treatment with purified protein phosphatase 2A. Furthermore, TAR RNA-binding activity can be partially restored to depleted nuclear extracts in vitro by addition of PKC. Chimeric constructs in which the Tat protein is artificially tethered to viral RNA show PKC independence for Tat mediated trans activation. Specific mutations in the TAR RNA stem region which cause reduced binding of host cell factor in vitro also cause reduced Tat mediated trans activation in vivo. Together, these results suggest that phosphorylation-dependent binding of a cellular cofactor to TAR RNA is an essential step in Tat-mediated trans activation. Deciphering the regulation of Tat-mediated trans activation by phosphorylation will be critical in fully understanding the regulation of human immunodeficiency virus type 1 activation. PMID- 1602532 TI - Structural basis of C3b binding by glycoprotein C of herpes simplex virus. AB - Glycoproteins C (gC) from herpes simplex virus type 1 (HSV-1) and HSV-2, gC-1 and gC-2, bind the human complement fragment C3b, although the two glycoproteins differ in their abilities to act as C3b receptors on infected cells and in their effects on the alternative complement pathway. Previously, we identified three regions of gC-2 (I, II, and III) which are important for C3b binding. In this study, our goal was to identify C3b-binding sites on gC-1 and to continue our analysis of gC-2. We constructed a large panel of mutants by using the cloned gC 1 and gC-2 genes. Most of the mutant proteins were transported to the surface of transiently transfected L cells and reacted with one or more monoclonal antibodies to discontinuous epitopes. By using 31 linker insertion mutants spread across the coding region of gC-1, we identified four regions in the ectodomain of gC-1 which are important for C3b binding, three of which are similar in position to C3b-binding regions I, II, and III of gC-2. Region III shares some similarities with the short consensus repeat found in CR1, the human complement receptor. These were, in part, the targets for construction of 20 single amino acid changes in region III of gC-1 and gC-2. These mutants identified similarities and differences in the C3b-binding properties of gC-1 and gC-2 and suggest that the amino half of region III is more important for C3b binding. However, our results do not support the concept of a structural relationship between the short consensus repeat of CR1 and gC, since mutations of some of the conserved residues, including three of four cysteines in region III, had no effect on C3b binding. Finally, we constructed four deletion mutants of gC-1, including one which lacked residues 33 to 123, as well as residues 367 to 449. This severely truncated molecule, lacking four cysteines and five potential N linked glycosylation sites, was transported to the cell surface and retained its ability to bind monoclonal antibodies as well as C3b. Thus, the four distinct C3b binding regions of gC-1 and several epitopes within two different antigenic sites are localized within residues 124 to 366. PMID- 1602534 TI - Transcriptional regulation of precore and pregenomic RNAs of hepatitis B virus. AB - Hepatitis B virus (HBV) infection, either acute or chronic, has been one of the leading health problems in the world. To understand the HBV life cycle and disease process, we set out to study the regulation of viral gene expression. In this paper, we report the characterization of the HBV core promoter: two 3.5-kb transcripts, precore and pregenomic, are made from it. The latter is itself a template for viral genome replication and also encodes viral proteins essential for both viral replication and virion assembly. We identify a short sequence (from nucleotides [nt] 1744 to 1851, referred to as the basic core promoter [BCP]) that is sufficient to direct correct initiation of both precore and pregenomic messages. In addition, the two appear to be regulated in a coordinate manner. Sequences upstream of the BCP (from nt 1636 to 1744, referred to as the core upstream regulatory sequence [CURS]), have a strong stimulating effect on the BCP. Addition of the CURS to the BCP leads to a dramatic increase in both the transcription of two 3.5-kb messages and the production of 42-nm virions from transiently transfected hepatoma cells. The CURS stimulates the BCP in a position and orientation-dependent manner. Therefore, it is unlikely that the effect is mediated through enhancer II, which has been localized to the same sequence. Deletion analysis of the CURS suggests that it contains multiple regulatory elements that control the BCP in an interactive manner. In accord with this hypothesis, the CURS is found to be bound with many distinct protein factors in footprinting experiments. Among these elements, box alpha (from nt 1646 to 1668) and box gamma delta (from nt 1671 to 1703) are two regulatory elements which individually stimulate promoter activity more than 100-fold. PMID- 1602535 TI - The arginine-rich domain of the hepatitis B virus core protein is required for pregenome encapsidation and productive viral positive-strand DNA synthesis but not for virus assembly. AB - Assembly of replication-competent hepatitis B virus (HBV) nucleocapsids requires the interaction of the core protein, the P protein, and the RNA pregenome. The core protein contains an arginine-rich C-terminal domain which is dispensable for particle formation in heterologous expression systems. Using transient expression in HuH7 cells of a series of C-terminally truncated core proteins, I examined the functional role of this basic region in the context of a complete HBV genome. All variants containing at least the 144 N-terminal amino acids were assembly competent, but efficient pregenome encapsidation was observed only with variants consisting of 164 or more amino acids. These data indicate that one function of the arginine-rich region is to provide the interactions between core protein and RNA pregenome. However, in cores from the variant ending with amino acid 164, the production of complete positive-strand DNA was drastically reduced. Moreover, almost all positive-strand DNA originated from in situ priming, whereas in wild type particles, this type of priming not supporting the formation of relaxed circular DNA (RC-DNA) accounted for about one half of the positive strands. Further C-terminal residues to position 173 restored RC-DNA formation, and the corresponding variant did not differ from the full-length core protein in all assays used. The observation that RNA encapsidation and formation of RC-DNA can be genetically separated suggests that the core protein, via its basic C-terminal region, also acts as an essential auxiliary component in HBV replication, possibly like a histone, or like a single-stranded-DNA-binding protein. In contrast to their importance for HBV replication, sequences beyond amino acid 164 were not required for the formation of enveloped virions. Since particles from variant 164 did not contain mature DNA genomes, a genome maturation signal is apparently not required for HBV nucleocapsid envelopment. PMID- 1602536 TI - The transmembrane glycoprotein of human immunodeficiency virus type 1 induces syncytium formation in the absence of the receptor binding glycoprotein. AB - To study the intracellular transport and biological properties of the human immunodeficiency virus type 1 (HIV-1) transmembrane glycoprotein (TM; gp41), we constructed a truncated envelope gene in which the majority of the coding sequences for the surface glycoprotein (SU; gp120) were deleted. Transient expression of this truncated env gene in primate cells resulted in the biosynthesis of two proteins with M(r)s of 52,000 and 41,000, respectively. Immunofluorescence studies with antibodies to the HIV-1 TM protein indicated that the intracellular and surface localization of these proteins were indistinguishable from those of the native HIV-1 gp120-gp41 complex. These results indicate that the oligosaccharide processing and cell surface transport of the HIV-1 TM protein were not dependent on the presence of the receptor binding subunit, gp120. Syncytium formation was readily detected upon expression of the deleted HIV-1 env gene into COS and CD4+ HeLa cell lines, suggesting that in the absence of gp120, the TM protein retained biological activity. This observation was confirmed by infection of primate and mouse cell lines with a recombinant vaccinia virus (vvgp41) expressing the truncated HIV-1 env gene. These results strongly suggest that (i) the two biological activities of the HIV 1 envelope glycoprotein can occur independently and (ii) the association of the two glycoprotein subunits may restrict the fusion activity of the transmembrane component to CD4+ cells. PMID- 1602537 TI - The human immunodeficiency virus type 1 packaging signal and major splice donor region have a conserved stable secondary structure. AB - Interaction of cis-acting RNA sequences with nucleocapsid proteins is one of the critical events leading to retroviral genomic RNA packaging. We have derived a potentially stable secondary structure for the packaging signal region of human immunodeficiency virus strain IIIB, using a combination of biochemical analysis and computer modelling. This region encompasses the major splice donor (SD), which is found in a highly structured conserved stem-loop. Comparison with other published human immunodeficiency virus type 1 sequences shows almost absolute nucleotide conservation in base-paired regions required to maintain this structure. Presently and previously described packaging-defective mutants would disrupt the structure. The structure depends on base pairing between nucleotide sequences 5' of the major SD which are common to both genomic and subgenomic RNAs and sequences 3' of SD which are unique to the unspliced RNA. This may explain how in retroviruses such as Rous sarcoma virus, mutations in regions common to genomic and subgenomic RNA might prevent packaging of the unspliced mRNA by disrupting a signal structure which can exist only in the genomic RNA species. PMID- 1602538 TI - Overexpression of the influenza virus polymerase can titrate out inhibition by the murine Mx1 protein. AB - The murine Mx1 protein is an interferon-inducible protein which confers selective resistance to influenza virus infection both in vitro and in vivo. The precise mechanism by which the murine Mx1 specifically inhibits replication of influenza virus is not known. Previously, sensitive replication systems for influenza virus ribonucleoprotein, in which a synthetic influenza virus-like ribonucleoprotein is replicated and transcribed by influenza virus proteins provided in trans, have been developed. With these systems, the antiviral activity of the murine Mx1 protein was examined. It was found that continued expression of influenza polymerase polypeptides via vaccinia virus vectors can titrate out the inhibitory action of the murine Mx1 protein. This titration of inhibitory activity also occurs when the viral PB2 protein alone is overexpressed, suggesting that an antiviral target for the murine Mx1 polypeptide is the viral PB2 protein. PMID- 1602540 TI - Role of cell-associated enveloped vaccinia virus in cell-to-cell spread. AB - The roles of intracellular naked (INV), cell-associated enveloped (CEV), and extracellular enveloped (EEV) forms of vaccinia virus in cell-to-cell and longer range spread were investigated by using two closely related strains of vaccinia virus, WR and IHD-J. We confirmed previous results that WR and IHD-J produced similar amounts of INV and formed similar-size primary plaques but that IHD-J produced 10 to 40 times more EEV and spread to distant cells much more efficiently than did WR. Nevertheless, cells infected with WR and IHD-J had similar amounts of CEV, indicating that wrapping and transport of WR virions were unimpaired. A WR mutant with a deletion in VP37, the major outer envelope protein, formed normal amounts of INV; however, the generation of CEV was blocked and plaque formation was inhibited. These results suggested that CEV is the form of virus that mediates cell-to-cell spread. Marker rescue experiments indicated that the differences in EEV production by WR and IHD-J were not due to sequence differences in VP37. The low amount of WR EEV could be attributed to retention of CEV on the cell membrane. In support of this hypothesis, mild treatment with trypsin released as much or more infectious virus from cells infected with WR as it did with cells infected with IHD-J. Most of the virus released by trypsin sedimented with the buoyant density of EEV. Also, addition of trypsin to cells following inoculation with WR led to a comet-shaped distribution of secondary plaques characteristic of IHD-J. These results demonstrated that the release of CEV from the cell surface was limiting for extracellular virus formation and affirmed the role of EEV in long-range spread. PMID- 1602539 TI - Intracellular processing of the paramyxovirus F protein: critical role of the predicted amphipathic alpha helix adjacent to the fusion domain. AB - At a nonpermissive temperature, the group D temperature-sensitive mutants of Newcastle disease virus strain Australia-Victoria (AV) are defective in plaque formation, in inducing infected cells to fuse, and in incorporating the cleaved fusion glycoprotein, F1 + F2, into virus particles. In this study, the F protein of AV, expressed in chicken embryo cells, was able to complement these mutants in a plaque assay, identifying the F gene as the gene containing the group D temperature-sensitive lesions. The F genes of mutants D1, D2, and D3 were found to contain single mutations relative to the AV sequence, clustered within a predicted amphipathic alpha helix (AAH) adjacent to the hydrophobic amino terminus of F1. These mutant F proteins were inefficiently processed at the permissive temperature, a problem that was exacerbated at the nonpermissive temperature. Surprisingly, the AV F protein was also found to be partially temperature sensitive in processing. Its AAH is predicted to contain a break in the helix close to the D mutation sites, which are themselves predicted to further weaken the helix at this point. Interestingly, six revertants of the group D mutants were found to have an additional lesion in the AAH, repairing both the AV and mutant helices, resulting in a predicted perfect helix. The F protein of these revertants had overcome both the processing defects of the mutants and the temperature sensitivity of AV, indicating that the AAH region is critical for F protein processing. The lesions of a second group of revertants were localized within F2, suggesting an interaction with the F1 AAH region containing the original lesion. PMID- 1602541 TI - Morphogenesis of Sindbis virus in three subclones of Aedes albopictus (mosquito) cells. AB - The morphogenesis of Sindbis virus in three Aedes albopictus subcloned cell lines was examined. Each line was distinguishable with respect to morphology, cytopathic response to infection, and progeny yield. C7-10 cells, which produced the highest titers of virus and exhibited the most severe cytopathic response, were characterized ultrastructurally by the presence of budding particles at the cell surface and at the membranes of internal vesicles. C6/36 cells, which displayed a moderate cytotoxic response, manifested similar features in response to Sindbis virus infection. Both cell types also produced a structure composed of an electron-dense matrix in which nucleocapsids were embedded. Internally matured virions were released by exocytosis from these cells. In addition to a lack of cytopathic effect, u4.4 cells also failed to exhibit obvious morphogenetic changes upon infection. Virus particles were occasionally seen within vesicles, but budding at the cell surface was not detected. The mechanism of release of internally matured virions was not apparent. These studies provide further evidence that these three subcloned mosquito cell lines represent different tissues in the larval or adult insect. PMID- 1602542 TI - Effect of retroviral proteinase inhibitors on Mason-Pfizer monkey virus maturation and transmembrane glycoprotein cleavage. AB - Mason-Pfizer monkey virus (M-PMV) is the prototype type D retrovirus which preassembles immature intracytoplasmic type A particles within the infected cell cytoplasm. Intracytoplasmic type A particles are composed of uncleaved polyprotein precursors which upon release are cleaved by the viral proteinase to their constituent mature proteins. This results in a morphological change in the virion described as maturation. We have investigated the role of the viral proteinase in virus maturation and infectivity by inhibiting the function of the enzyme through mutagenesis of the proteinase gene and by using peptide inhibitors originally designed to block human immunodeficiency virus type 1 proteinase activity. Mutation of the active-site aspartic acid, Asp-26, to asparagine abrogated the activity of the M-PMV proteinase but did not affect the assembly of noninfectious, immature virus particles. In mutant virions, the transmembrane glycoprotein (TM) of M-PMV, initially synthesized as a cell-associated gp22, is not cleaved to gp20, as is observed with wild-type virions. This demonstrates that the viral proteinase is responsible for this cleavage event. Hydroxyethylene isostere human immunodeficiency virus type 1 proteinase inhibitors were shown to block M-PMV proteinase cleavage of the TM glycoprotein and Gag-containing precursors in a dose-dependent manner. The TM cleavage event was more sensitive than cleavage of the Gag precursors to inhibition. The infectivity of treated particles was reduced significantly, but experiments showed that inhibition of precursor and TM cleavage may be at least partially reversible. These results demonstrate that the M-PMV aspartyl proteinase is activated in released virions and that the hydroxyethylene isostere proteinase inhibitors used in this study exhibit a broad spectrum of antiretroviral activity. PMID- 1602543 TI - Transcellular activation of the human immunodeficiency virus type 1 long terminal repeat in cocultured lymphocytes. AB - One of the unexplained aspects of the progression of AIDS is that immunological abnormalities are detectable before CD4+ T-helper cell depletion occurs (A.R. Gruters, F.G. Terpstra, R. De Jong, C.J.M. Van Noesel, R.A.W. Van Lier, and F. Miedema, Eur. J. Immunol. 20:1039-1044, 1990; F. Miedema, A.J. Chantal-Petit, F.G. Terpstra, J.K.M.E. Schattenkerk, F. de Wolf, B.J.M. Al, M. Roos, J.M.A. Lang, S.A. Danner, J. Goudsmit, and P.T.A. Schellekens, J. Clin. Invest. 82:1908 1914, 1988; G.M. Shearer, D.C. Bernstein, K.S. Tung, C.S. Via, R. Redfield, S.Z. Salahuddin, and R.C. Gallo, J. Immunol. 137:2514-2521, 1986). In this report, we describe a mechanism by which human immunodeficiency virus type 1 (HIV-1) infected cells can influence neighboring HIV-1-infected T lymphocytes and uninfected T cells as well. We have examined the interaction of T-cell and macrophage cell lines that are transfected with HIV-1 DNA by using cocultured lymphocytes. The HIV-1 constructs we used lack a functional pol gene and therefore do not produce infectious virus. Cocultivation results in the transcellular activation of the HIV long terminal repeat in the cocultured T cells. This transcellular activation is evident in as little as 3 h of cocultivation, at ratios of HIV-expressing cells to target cells as low as 1:1,000, and is dependent on the Tat-responsive element. The demonstration that a small number of HIV-expressing cells can affect a large number of uninfected bystander cells in a short period of time suggests a mechanism by which global immune dysfunction can precede the high prevalence of infected cells. PMID- 1602544 TI - Inhibition of virus production in peripheral blood mononuclear cells from human immunodeficiency virus (HIV) type 1-seropositive donors by treatment with recombinant HIV-like particles. AB - We have previously reported on the assembly of recombinant human immunodeficiency virus (HIV)-like particles that contain gag structural proteins and present env glycoproteins gp120 and gp41 on their surfaces (O. Haffar,. J. Garriques, B. Travis, P. Moran, J. Zarling, and S.-L. Hu, J. Virol. 64:2653-2659, 1990). On the basis of their structures, we hypothesized that the recombinant particles would interfere with virus infection and tested our hypothesis in vitro by using peripheral blood mononuclear cells (PBMC) from HIV type 1-seropositive donors. Addition of the recombinant particles to PBMC concomitant with stimulation by anti-CD3 inhibited virus production, as determined by reduced levels of p24 in the culture supernatants. This inhibition of p24 production correlated with lower levels of cell-associated viral DNA. Several lines of evidence suggested that the recombinant particles exerted their antiviral effects primarily by inhibiting virus production from latently infected cells and not by inhibiting subsequent virus spread. Importantly, CD4+ T-cell stimulation by specific antigen or by anti CD3 was not inhibited by treatment with the recombinant particles. This apparent selective inhibition of virus replication in infected PBMC represents a novel property of the recombinant HIV-like particles. PMID- 1602545 TI - Comparative analysis of Rev function in human immunodeficiency virus types 1 and 2. AB - The Rev proteins of the related but distinct human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) display incomplete functional reciprocity. One possible explanation for this observation is that HIV-2 Rev is unable to interact with the HIV-1 Rev-response element (RRE1). However, an analysis of the biological activity of chimeric proteins derived from HIV-1 and HIV-2 Rev reveals that this target specificity does not map to the Rev RNA binding domain but is instead primarily determined by sequences known to mediate Rev multimerization. Both HIV 1 and HIV-2 Rev are shown to bind the RRE1 in vitro with identical RNA sequence specificity. The observation that HIV-2 Rev can inhibit RRE1-dependent HIV-1 Rev function in trans indicates that the direct interaction of HIV-2 Rev with the RRE1 also occurs in vivo. These data suggest that HIV-2 Rev forms a protein-RNA complex with the RRE1 that leads to only minimal Rev activity. It is hypothesized that this low level of Rev function results from the incomplete and/or aberrant multimerization of HIV-2 Rev on this heterologous RNA target sequence. PMID- 1602547 TI - Mutational analysis of the promoter required for influenza virus virion RNA synthesis. AB - An in vitro RNA synthesis system was established in which the influenza virus virion (minus-sense) RNA was made from the synthetic plus-sense RNA (cRNA) template by the purified viral polymerase complex. The cRNA promoter was studied by mutational analysis using the in vitro system, and on the basis of these experiments, the first 11 nucleotides of the 3' noncoding sequence were found to contain the minimum promoter required for virion RNA synthesis. The addition of extra nucleotides at the 3' end decreased the promoter activity of the templates, indicating that the viral polymerase does not recognize an internal promoter efficiently. The wild-type and mutated RNA templates were also tested in vivo by using the ribonucleoprotein transfection system. In contrast to the in vitro system, it was found that the majority of mutations at the 3'-terminal sequence significantly decreased or abolished chloramphenicol acetyltransferase (CAT) expression. These results suggest that the cRNA promoter overlaps other essential cis elements required for chloramphenicol acetyltransferase expression in vivo. PMID- 1602546 TI - Phosphorylation regulates RNA binding by the human T-cell leukemia virus Rex protein. AB - The Rex protein of human T-cell leukemia virus types I (HTLV-I) and II (HTLV-II) regulates the expression of the viral structural genes and is critical for viral replication. Rex acts by specifically binding to RNAs containing sequences of the R region of the 5' long terminal repeat. Two forms of Rex detected in HTLV-II infected cells, p26rex and p24rex, differ in the extent of serine phosphorylation. Two-dimensional phosphopeptide analysis indicates that p26rex is extensively phosphorylated at multiple sites. Using a sensitive immunobinding assay, we show that the phosphorylation state of Rex determines the efficiency of binding of Rex to HTLV-II target RNAs. Thus, the phosphorylation state of Rex in the infected cell may be a switch that determines whether virus exists in a latent or productive state. These studies also suggest that phosphorylation of RNA-binding regulatory proteins is a more general mechanism of gene regulation. PMID- 1602548 TI - Generation and analysis of defective genomes of Autographa californica nuclear polyhedrosis virus. AB - We have generated defective genomes of Autographa californica nuclear polyhedrosis virus (AcNPV) by serial, undiluted passage in IPLB-SF-21 cell culture in an attempt to identify potential cis-acting sequences important for AcNPV DNA replication. Viral DNA isolated from some of the 81 serial passages was analyzed by pulsed-field gel electrophoresis, restriction endonuclease analysis, and Southern blot hybridization. AcNPV-defective genomes appeared to be generated through a series of successively smaller and transiently stable intermediates. Although the defective genomes at passages later than passage 65 (P65) were somewhat heterogeneous in size, those of the majority of the population had a mean size estimated to be 50 kb, or 40% of that of standard virus. Defective genomic DNA at P81 hybridized strongly only to a 2.8-kb region mapping within 85.0 to 87.2 map units of AcNPV DNA (most of HindIII-K and a small part of HindIII-B), suggesting that the majority of P81-defective genomes were missing most of the 128-kb wild-type DNA sequence, except for this small 2.8-kb fragment. Furthermore, our results indicated that the defective genomes of P81 were composed largely of reiterations of this sequence. We suggest that the 2.8-kb DNA segment retained by the defective AcNPV genomes of P81 contains an important cis acting element(s) sufficient for viral DNA replication in AcNPV-infected cells. PMID- 1602549 TI - Two distinct serum mannose-binding lectins function as beta inhibitors of influenza virus: identification of bovine serum beta inhibitor as conglutinin. AB - Normal bovine and mouse sera contain a component, termed beta inhibitor, that inhibits the infectivity and hemagglutinating activity of influenza A viruses of the H1 and H3 subtypes. We have previously shown these beta inhibitors to be mannose-binding lectins that apparently act by binding to carbohydrate on the viral hemagglutinin, blocking access of the receptor-binding site to receptors on host cells (E. M. Anders, C. A. Hartley, and D. C. Jackson, Proc. Natl. Acad. Sci. USA 87:4485-4489, 1990). For the H3-subtype virus A/Memphis/1/71 x A/Bel/42 (H3N1), sensitivity to beta inhibitors is determined by the oligosaccharide at residue 165 of the hemagglutinin, this glycosylation site being lost in a resistant mutant selected by growth in the presence of bovine serum. In the present study, we sequenced the hemagglutinin genes of additional bovine serum resistant mutants derived from influenza viruses A/Philippines/2/82 (H3N2) and A/Brazil/11/78 (H1N1). The results confirm the importance of carbohydrate at residue 165 for inhibitor sensitivity of H3 viruses and implicate carbohydrate at residue 87 (94a in the H3 numbering system) as an important determinant in the sensitivity of H1-subtype viruses to the bovine inhibitor. Unlike the two H3 mutants, which had also gained resistance to hemagglutination inhibition by mouse serum, the H1 bovine serum-resistant mutant remained sensitive to the mouse beta inhibitor, suggesting that inhibition by the two types of sera is mediated by distinct mannose-binding lectins. In support of this hypothesis, the beta inhibitors in bovine and mouse sera were shown to differ in their pattern of inhibition by monosaccharides and in their sensitivity to 2-mercaptoethanol. In these and other properties, the bovine inhibitor closely resembled conglutinin, a Ca(2+)-dependent N-acetylglucosamine- and mannose-binding lectin present in bovine serum but absent from the serum of other species. Furthermore, polyclonal and monoclonal anticonglutinin antibodies abrogated the hemagglutination inhibiting activity of bovine serum. Direct binding of conglutinin to the parent viruses and reduced binding to their respective mutants were confirmed by radioimmunoassay. PMID- 1602550 TI - Conservation of RNA-protein interactions among picornaviruses. AB - Picornavirus genomes encode unique 5' noncoding regions (5' NCRs) which are approximately 600 to 1,300 nucleotides in length, contain multiple upstream AUG codons, and display the ability to form extensive secondary structures. A number of recent reports have shown that picornavirus 5' NCRs are able to facilitate cap independent internal initiation of translation. This mechanism of translation occurs in the absence of viral gene products, suggesting that the host cell contains the necessary components for the cap-independent internal initiation of translation of picornavirus RNAs as well as cellular mRNAs. In an attempt to identify some of the perhaps novel cellular proteins involved in this newly discovered mechanism of translation, we utilized RNA mobility shifts assays to identify and characterize interactions that occur between the 5'NCR of poliovirus type 1 (PV1) and cellular proteins. In this report, we describe two separate interactions between RNA structures from the 5' NCR of PV1 and proteins present in extracts from HeLa cells as well as other cell types. We describe the interaction between nucleotides 186 to 220 (stem-loop D) and a cellular protein(s) present in HeLa cell extracts. Mutational analysis of this stem-loop structure suggests that maintenance of a base-paired structure in the lower stem is necessary to present the sequences which directly interact with the protein(s). We also describe the interaction between nucleotides 220 to 460 (stem loop E) and a cellular protein present in HeLa cell extracts. This RNA binding activity fractionates to a specific ammonium sulfate fraction (A cut) of a ribosomal salt wash. Mutational analysis of the stem-loop E structure suggests that the preservation of an extensive RNA structure is necessary for a strong interaction with the cellular protein(s), although smaller RNAs derived from this region of the 5' NCR can interact to lesser extents. Finally, we show that both of these RNA-protein interactions are conserved among the closely related enteroviruses PV1 and coxsackievirus type B3, human rhinovirus type 14, and the more distantly related cardiovirus Theiler's murine encephalomyelitis virus, suggesting that such RNA-protein interactions serve basic functions which are conserved and utilized by each of these picornaviruses. PMID- 1602551 TI - Vaccinia virus B1 kinase: phenotypic analysis of temperature-sensitive mutants and enzymatic characterization of recombinant proteins. AB - The vaccinia virus B1 gene encodes a 34-kDa protein with homology to protein kinases. In L cells infected nonpermissively with mutants containing lesions in the B1 gene (ts2 and ts25), the infectious cycle arrests prior to DNA replication. In this report, we demonstrate that DNA synthesis ceases when cultures infected with these mutants at 32 degrees C are shifted to the nonpermissive temperature (39.5 degrees C) in the midst of DNA replication. We also show that B1 protein is synthesized transiently during the early phase of infection, even when the progression to later stages of gene expression is prevented. Although wild-type (wt) B1 is stable, the ts B1 proteins are markedly labile in both L and BSC40 cells at both permissive and nonpermissive temperatures. These results suggest that the ts phenotype of the mutants is complex and may in part reflect a temperature-dependent requirement for kinase activity, an induction of temperature sensitivity in B1 substrates under nonpermissive conditions, and/or ts complementation by host factors. To facilitate biochemical analyses, recombinant wt B1, ts2 B1, and ts25 B1 were produced in Escherichia coli. The wt protein was able to phosphorylate serine and threonine residues on several exogenous substrates in vitro. The activity of ts25 B1 was 3% that of the wt enzyme, and no detectable kinase activity was associated with ts2 B1. In light of the inactivity of the ts2 B1 protein in vitro and its extreme lability in vivo, we attempted to isolate a vaccinia virus B1 null mutant by targeted interruption of the B1 gene at 32 degrees C. No null mutants were isolated. These results indicate that the B1 protein kinase provides a vital function which cannot be supplied by the host or circumvented by incubation at 32 degrees C. PMID- 1602553 TI - Effect of gamma radiation on retroviral recombination. AB - To elucidate the mechanism(s) of retroviral recombination, we exposed virions to gamma radiation prior to infecting target cells. By using previously described spleen necrosis virus-based vectors containing multiple markers, recombinant proviruses were studied after a single round of retrovirus replication. The current models of retroviral recombination predict that breaking virion RNA should promote minus-strand recombination (forced copy-choice model), decrease or not affect plus-strand recombination (strand displacement/assimilation model), and shift plus-strand recombination towards the 3' end of the genome. However, we found that while gamma irradiation of virions reduced the amount of recoverable viral RNA, it did not primarily cause breaks. Thus, the frequency of selected recombinants was not significantly altered with greater doses of radiation. In spite of this, the irradiation did decrease the number of recombinants with only one internal template switch. As a result, the average number of additional internal template switches in the recombinant proviruses increased from 0.7 to 1.4 as infectivity decreased to 6%. The unselected internal template switches tended to be 5' of the selected crossover even in the recombinants from irradiated viruses, inconsistent with a plus-strand recombination mechanism. PMID- 1602552 TI - Changes in both gp120 and gp41 can account for increased growth potential and expanded host range of human immunodeficiency virus type 1. AB - Virus derived from an infectious molecular clone of the ELI strain of human immunodeficiency virus type 1 (HIV-1) replicates well in peripheral blood mononuclear cells and in some CD4-positive cell lines but exhibits a delayed time course of infection in CEM and H9 cells and fails to infect SupT1 and U937 cells. If the virus that emerges from infected H9 cells is used to infect CEM and H9 cells, the time course of infection is accelerated and the virus is able to infect U937 and SupT1 cells. In this study, we used the technique of polymerase chain reaction-single-strand conformation polymorphism to localize changes in both the extracellular gp120 and the transmembrane gp41 components of the envelope gene associated with adaptation to growth in tissue culture cell lines. Specifically, mutations were identified both in a region of gp120 implicated in CD4 binding and in the amino-terminal portion of gp41 adjacent to the region involved in fusion. No changes were found in the V3 loop of gp120, a region previously shown to be involved in viral tropism. When these mutations were introduced into the original molecular clone, they conferred an enhanced replicative capacity on ELI. These results demonstrate that two additional determinants in the HIV-1 envelope protein influence viral tropism and growth in vitro. They also may have important implications for the generation of viruses with increased growth potential and expanded host range seen in the late stages of HIV disease. PMID- 1602554 TI - Neutralization of multiple laboratory and clinical isolates of human immunodeficiency virus type 1 (HIV-1) by antisera raised against gp120 from the MN isolate of HIV-1. AB - Vaccines prepared from the envelope glycoprotein, gp120, of the common laboratory isolate of human immunodeficiency virus type 1 (HIV-1) (IIIB/LAV-1) elicit antibodies that neutralize the homologous virus but show little if any cross neutralizing activity. This may be because the principal neutralizing determinant (PND) of gp120 is highly unusual in the IIIB/LAV-1 strain and is not representative of those found in the majority of field isolates. We have now examined the immunogenicity of recombinant gp120 prepared from the MN strain of HIV-1 (MN-rgp120), whose PND is thought to be representative of approximately 60% of the isolates in North America. Our results show that MN-rgp120 is a potent immunogen and elicits anti-gp120 titers comparable to those found in HIV-1 infected individuals. While both MN-rgp120 and IIIB-rgp120 induced antibodies able to block gp120 binding to CD4, strain-specific and type-common blocking antibodies were detected. Finally, antibodies to MN-rgp120 but not to IIIB-rgp120 were effective in neutralizing a broad range of laboratory and clinical isolates of HIV-1. These studies demonstrate that susceptibility or resistance to neutralization by antibodies to gp120 correlates with the PND sequence and suggest that the problem of antigenic variation may not be insurmountable in the development of an effective AIDS vaccine. PMID- 1602555 TI - Premature termination and processing of human immunodeficiency virus type 1 promoted transcripts. AB - We have used transient expression assays to study transcription directed by the human immunodeficiency virus (HIV) type 1 promoter. A plasmid containing an HIV reporter gene fusion and a simian virus 40 origin of DNA replication was transfected into COS-1 cells in the presence or absence of a Tat expression vector. HIV-promoted RNA was analyzed by in vivo labeling, by RNase protection mapping, and in run-on transcription assays. As observed previously, two populations of HIV RNA accumulate in vivo: short, attenuated transcripts and long, polyadenylated mRNA. The short transcripts labeled in vivo were longer and more heterogeneous than expected from RNase protection assays. Moreover, comparison of transcripts labeled in vivo with run-on transcription products revealed that similar, if not identical, short RNAs accumulate in vitro. Utilizing the run-on assay, we show that following transcriptional termination, the attenuated transcripts undergo processing to generate one species of RNA. We also provide evidence that Tat does not act as an antiterminator to relieve a discrete elongation block but instead modifies transcriptional complexes, enabling them to overcome putative pause sites and continue transcription of the template. PMID- 1602557 TI - Localization to the Golgi complex of Uukuniemi virus glycoproteins G1 and G2 expressed from cloned cDNAs. AB - The membrane glycoproteins G1 and G2 of Uukuniemi virus, a bunyavirus, accumulate in the Golgi complex (GC) during virus infection. These proteins have therefore been considered to be good models for studying the intracellular transport to and retention in the GC. In this study, I have used indirect immunofluorescence to localize in COS cells the Uukuniemi virus glycoproteins G1 and G2 expressed together or separately from cloned cDNAs with use of simian virus 40-based vectors. When expressed together from the full-length cDNA, G1 and G2 were correctly translocated, processed, and targeted to the GC, indicating that the information for GC targeting resides in the proteins. When the proteins were expressed separately, G1 was transported to the GC and retained there. In contrast, G2 could not be detected in the GC but was most probably retained and finally degraded in the endoplasmic reticulum. However, in cells cotransfected with G1 and G2 cDNAs, the proteins could both again be found in the GC. These results suggest that G1 is a responsible for targeting to and retention of the Uukuniemi virus glycoproteins in the GC. G2 would thus accumulate in the GC by virtue of its binding to G1. PMID- 1602556 TI - Influence of Theiler's murine encephalomyelitis virus 5' untranslated region on translation and neurovirulence. AB - The DA strain of Theiler's murine encephalomyelitis virus (TMEV), a picornavirus, causes a persistent, restricted infection and demyelinating disease in mice. In contrast, the GDVII strain causes an acute, fatal, neuronal disease and is highly neurovirulent. To investigate the role of the TMEV 5' untranslated region (UTR) in translational efficiency and the TMEV subgroup differences, we tested the translational efficiency of transcripts in vitro derived from plasmids containing DA, GDVII, or DA/GDVII chimeric 5' UTRs preceding a reporter gene or the rest of the TMEV genome. We demonstrated that GDVII RNA translates more efficiently in rabbit reticulocyte lysate than DA RNA and that this enhanced translation is mediated by multiple domains in the GDVII 5' UTR as well as a region of the genome outside of the 5' UTR. We also identified a region within DA nucleotides 14 to 395 which inhibits translation of DA RNA and could contribute to the persistent, restricted DA central nervous system infection; the predicted secondary structure of the 5' UTR demonstrates a remarkable stem-loop structure within this region that is relatively unique among picornaviruses. Data from experiments involving DA/GDVII chimeric 5' UTR full-length infectious cDNA clones suggested that sequences in the 5' UTR can affect the neurovirulence phenotype but that translational efficiency is necessary but not sufficient for neurovirulence. These studies emphasize the multigenic nature of neurovirulence and the importance of translation in the regulation of picornaviral gene expression. PMID- 1602558 TI - Role of the fusogenic peptide sequence in syncytium induction and infectivity of human immunodeficiency virus type 2. AB - Syncytium induction is a characteristic feature of infection by human immunodeficiency virus (HIV) in vitro. The hydrophobic amino terminus of the transmembrane glycoprotein of HIV type 1 is an essential determinant of virus entry into the target cell population and the formation of syncytia in cell culture. To define the role of the HIV type 2 fusion peptide during infection and syncytium formation, we introduced 8 amino acid substitutions into the hydrophobic amino terminus of gp41, changing either the hydrophobicity, the charge, or the polarity of the amino acid. Viruses containing the envelope mutations were analyzed for their syncytium-inducing capacities, levels of infectivity, and envelope processing and expression. Mutations that increased the hydrophobic nature of the fusion peptide increased syncytium formation, whereas mutations which increased the charge and the polarity and/or decreased the hydrophobicity of the fusion domain severely reduced the capacity of the virus to induce syncytia. However, viruses severely compromised for syncytium formation exhibit only slightly lower levels of infectivity. PMID- 1602559 TI - Dominant-negative mutants are clustered in a domain of the human T-cell leukemia virus type I Rex protein: implications for trans dominance. AB - The 27-kDa Rex trans-acting protein appears to be essential for replication of human T-cell leukemia virus type I. Mutations introduced outside of the Rex RNA binding domain-nucleolar localization signal display either wild-type activity or, conversely, yield dominant-negative proteins. We generated missense mutations in a particular domain of the Rex protein (amino acid residues 54 to 69) which is characterized by a cluster of dominant-negative mutants. Our results indicate that amino acids 57 to 67 are critically important for Rex function mediated through the RxRE cis-acting RNA sequence. Within this domain, only amino acids 61 to 63 could be mutated without loss of function. All other missense and deletion mutants yielded dominant-negative proteins. In vitro RNA-binding studies performed with glutathione S-transferase-Rex fusion proteins demonstrated that all of the mutant Rex proteins interacted specifically with RxRE RNA. Analysis of chimeric Rex-Rev proteins suggests that this Rex domain is important for oligomerization. PMID- 1602560 TI - In vivo genetic variability of the human immunodeficiency virus type 2 V3 region. AB - The principal neutralizing epitope of the human immunodeficiency virus type 1 (HIV-1) lies between two invariant cysteines in the third variable region (V3) of the viral envelope (gp120), and its amino acid sequence varies among different HIV-1 isolates. HIV-2 carries an analogous amino acid sequence between two cysteines of the V3 regions, but its functional similarity with the HIV-1 principal neutralizing epitope is uncertain. We studied the degree of genetic variation of the HIV-2 V3 region in fresh blood samples from 12 HIV-2 seropositive individuals from Guinea-Bissau. Polymerase chain reaction was used to amplify viral fragments of 465 bp containing the V3 region from cellular DNA. Nucleotide sequence analysis of the entire envelope fragment from each patient revealed that the degree of variation among field isolates of HIV-2 is comparable to that observed in the analogous region of HIV-1. Most of the HIV-2 isolates studied were highly related, suggesting the existence of a limited number of different viral strains in the cohort studied. Thus, the HIV-2 and HIV-1 V3 regions vary to a similar degree and may also have analogous functions. PMID- 1602561 TI - Biological activity of paramyxovirus fusion proteins: factors influencing formation of syncytia. AB - The fusion (F) and hemagglutinin-neuraminidase (HN) glycoproteins of the paramyxovirus simian virus 5 (SV5) were expressed individually or coexpressed in CV-1 cells by using SV40-based vectors and recombinant vaccinia viruses. The extent of detectable fusion in a syncytium formation assay was found to be affected by the expression system used. In addition, when HN was coexpressed with F, it was found that the expression vector system influenced the contribution of HN in forming syncytia. The abilities of the SV5, human parainfluenza virus type 3, and Newcastle disease virus F glycoproteins to cause fusion, when expressed alone or coexpressed with HN, were directly compared by using the SV40-based vector system in CV-1 cells. The F proteins exhibited various degrees of fusion activity independent of HN expression, but the formation of syncytia could be enhanced to different extents by the coexpression of the homotypic HN protein. PMID- 1602562 TI - Lymphocyte-facilitated infection of epithelia by human T-cell lymphotropic virus type I. AB - After the addition of human T-cell lymphotropic virus type I (HTLV-I)-infected lymphocytes to enterocyte monolayers, the lymphocytes adhered via microvilli from both cell types and shed virus onto the enterocyte surface. Virus fused with the epithelial membrane and infected these cells as confirmed by electron microscopic immunocytochemistry, in situ hybridization, and amplification by polymerase chain reaction. PMID- 1602563 TI - Human chromosome 12 is required for optimal interactions between Tat and TAR of human immunodeficiency virus type 1 in rodent cells. AB - Levels of trans activation of the human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) by the virally encoded transactivator Tat show marked species-specific differences. For example, levels of transactivation observed in Chinese hamster ovary (CHO) rodent cells are 10-fold lower than those in human cells or in CHO cells that contain the human chromosome 12. Thus, the human chromosome 12 codes for a protein or proteins that are required for optimal Tat activity. Here, the function of these cellular proteins was analyzed by using a number of modified HIV-1 LTRs and Tats. Neither DNA-binding proteins that bind to the HIV-1 LTR nor proteins that interact with the activation domain of Tat could be implicated in this defect. However, since species-specific differences were no longer observed with hybrid proteins that contain the activation domain of Tat fused to heterologous RNA-binding proteins, optimal interactions between Tat and the trans-acting responsive RNA (TAR) must depend on this factor(s). PMID- 1602564 TI - Evolution of the V3 envelope domain in proviral sequences and isolates of human immunodeficiency virus type 1 during transition of the viral biological phenotype. AB - The third variable domain (V3) of the envelope gene of human immunodeficiency virus type 1 contains a major neutralization epitope and determinants of syncytium-inducing (SI) capacity and replication rate (reviewed by J. P. Moore and P. L. Nara, AIDS Suppl. 2:S21-S33, 1991). Sequences were generated from DNA of samples taken 3 months apart over a period of 24 and 30 months from peripheral blood mononuclear cells (PBMC) of two individuals, both before and after cocultivation with uninfected donor PBMC. The isolated virus shifted from the non syncytium-inducing (NSI) phenotype to the SI phenotype during the study period. This shift was associated with distinct changes in the V3 domain in both patients. The association of the phenotype shift with the V3 sequence changes was confirmed by construction of viruses with chimeric V3 loops. The shift from NSI- to SI-associated V3 variants was also seen in the uncultured PBMC of both patients, but not until 3 and 9 months after the detection of SI virus in culture. In the samples of uncultured PBMC DNA, several subgroups of sequences were found, indicating that the process of evolution may not be gradual and that several distinct populations can coexist. The paucity of intermediate sequences indicated that strong selection pressure was exerted on this part of the envelope. The early emergence of disease-associated SI variants in cultured material indicates that virus culture may have relevance for the in vivo situation. PMID- 1602565 TI - Paratuberculosis in saiga antelope (Saiga tatarica) and experimental transmission to domestic sheep. AB - Mycobacterium paratuberculosis was isolated in low numbers from the small intestine and associated mesenteric lymph nodes of a saiga antelope (Saiga tatarica) using routine culture techniques in spite of histologic evidence of high numbers of acid-fast bacteria in these tissues. Two newborn domestic sheep were fed the ground intestinal tissue containing acid-fast bacteria and the progression of the experimental disease was followed by fecal culture, immunodiffusion (AGID) and lymphocyte stimulation (LST) tests. One experimentally infected sheep developed progressive clinical illness 1 yr postinoculation. Few M. paratuberculosis were isolated from feces or tissues although an extensive granulomatous mycobacterial enteritis, lymphadenitis and lymphangitis were observed containing large numbers of typical acid-fast organisms. No clinical illness was observed in the second inoculated sheep after 18 mo of observation, although infection was demonstrated at necropsy. Both sheep developed AGID and LST reactions indicative of paratuberculosis. This study demonstrated that a difficult to culture isolate of M. paratuberculosis was responsible for paratuberculosis in captive wild ruminants and was transmissible to domestic sheep. Diagnosis of paratuberculosis in four of eight of the imported saiga antelope and in eleven of their 18 offspring indicates the importance of this disease in management of captive wild ruminants and the ease with which this organism can be transmitted. PMID- 1602566 TI - Chlamydial-caused infectious keratoconjunctivitis in bighorn sheep of Yellowstone National Park. AB - An epizootic of infectious keratoconjunctivitis occurred in bighorn sheep (Ovis canadensis) in Yellowstone National Park during the winter of 1981-82. The causative organism was identified as Chlamydia sp. Mortality related to the epizootic was approximately 60% of an estimated 500 bighorn sheep in the northern range population. The infection probably affected all sex and age classes, but field surveys of live animals and mortality suggested that mature rams died disproportionately. Limited field observations the following winter on individuals having both normal and cloudy-appearing eyes suggested that half of the bighorns then present on the core units of winter range had contracted the disease and survived. By 1988, there were about 300 bighorn sheep in the population. PMID- 1602567 TI - Seroprevalence of Lyme disease in gray wolves from Minnesota and Wisconsin. AB - To determine the seroprevalence of Lyme disease in gray wolves (Canis lupus) from various counties of Minnesota and Wisconsin (USA), 589 serum samples were collected from 528 wolves from 1972 to 1989. An indirect fluorescent antibody (IFA) test was used to detect the presence of antibodies against Borrelia burgdorferi. Titers of greater than or equal to 1:100 were considered positive. Results were confirmed by testing a few selected sera by Western blotting. Of the 589 sera tested, 15 (3%) had IFA titers of greater than or equal to 1:100. Three of the positive samples were collected from Douglas County in Wisconsin and twelve were from Minnesota counties. This study indicates that wolves are exposed to B. burgdorferi and are susceptible to Lyme disease. PMID- 1602568 TI - Experimental Fascioloides magna infections of mule deer (Odocoileus hemionus hemionus). AB - Six mule deer (Odocoileus hemionus hemionus) and one white-tailed deer (Odocoileus virginianus), approximately 5-mo-old, each were inoculated orally with 500 metacercariae of Fascioloides magna. All mule deer died from liver fluke infection between 69 and 134 days (mean = 114, SE = 9.9) after inoculation. Between 38 and 326 immature F. magna (mean = 102, SE = 45.5) were recovered from each deer at necropsy. Flukes were present in livers, lungs, and free in pleural and peritoneal spaces. Infection was characterized by necrotizing hepatitis, fibrosing peritonitis and pleuritis, and hematin pigment accumulation in liver, lung, and many other internal organs. Eggs of F. magna first were detected in feces of the white-tailed deer 28 wk after inoculation, and weekly thereafter until the healthy deer was euthanized at 31 wk. At necropsy, 205 F. magna, including 12 encapsulated mature and 193 nonencapsulated immature flukes were recovered from liver, lungs, and free in abdominal and thoracic spaces of the white-tailed deer. Based on these results, F. magna may be fatal to mule deer within 5 mo of infection. Like domestic sheep and goats, mule deer may be highly susceptible to infection, and it is unlikely mule deer can survive infection with large numbers of F. magna. PMID- 1602569 TI - Tick infestation of baboons (Papio ursinus) in the Namib Desert. AB - Chacma baboons (Papio ursinus) living in an arid environment in Namibia were heavily infested with ticks of the genus Rhipicephalus. A survey to assess tick numbers and identity was undertaken in the baboons' habitat. It appears that there is a strong correlation between the number of ticks and the amount of time the baboons spend in an area. It is speculated that tick infestations were responsible for more than half (n = 18) of recorded infant deaths amongst these baboons. PMID- 1602570 TI - Spatial and seasonal distribution of potential vectors of hemorrhagic disease viruses to peninsular bighorn sheep in the Santa Rosa Mountains of southern California. AB - Blood-feeding midges (Culicoides sp. and Leptoconops sp.) were sampled in the Santa Rosa Mountains, Riverside County, California (USA), to determine which species might be involved in the transmission of bluetongue and epizootic hemorrhagic disease viruses to peninsular bighorn sheep (Ovis canadensis cremnobates). Host-seeking midges were sampled with CO2-baited suction traps over a period of 30 mo. Nineteen species of Culicoides and seven of Leptoconops were collected. Five of the Culicoides sp. recovered are previously undescribed. The most abundant and widely distributed Culicoides sp. during spring (presumed virus transmission period to lambs) were C. (Selfia) brookmani, C. variipennis, C. (Avaritia) sp. (a new species near C. pusillus), and C. lahontan. Of these, C. brookmani (all elevations) and C. (Avaritia) sp. (elevations greater than 750 m) were common in the mountainous terrain inhabited by bighorn sheep. Culicoides variipennis, a vector of bluetongue virus in agricultural settings, and C. lahontan were numerous in sandy washes but were much less common in the mountains themselves. Leptoconops belkini and L. foulki were occasionally common in upper Deep Canyon in spring (April-June), while L. torrens was very abundant in the same area for 2 wk following heavy summer rains. Parity (an indicator of longevity and success in finding hosts and oviposition sites) in mountain areas was very low in C. variipennis (5%), low-moderate in C. (Avaritia) sp. (13%) and C. lahontan (21%), and relatively high in C. brookmani (40%). Vectorial capacity of Culicoides spp. for these hemorrhagic disease viruses is discussed, and it is suggested that species in addition to C. variipennis be considered as potential vectors of hemorrhagic disease viruses to desert bighorn sheep. PMID- 1602571 TI - Was disease involved in the decimation of Guam's avifauna? AB - Between 1982 and 1986, 402 (290 live, 112 dead) exotic, migrant or native resident birds on Guam were surveyed for disease-causing agents to determine the role of disease in the decline of native forest bird populations on Guam. Traumatic injury, primarily from collisions with motor vehicles and predation, was the most prevalent (46%) cause of death. Thirty-eight percent of the carcasses examined were in poor body condition largely as a result of inadequate nutrition in captive native birds and poultry and adipose exhaustion in errant migrants. A variety of commensal or opportunistic bacteria, including Salmonella spp., were cultured from 220 birds, and nothing remarkable was found in 15 fecal samples. Lastly, no haematozoans, the suspected cause for the decline of the Hawaiian avifauna, were observed in blood slides examined from 260 birds. Based on the results of the survey and other lines of evidence presented in the discussion, we concluded there were no data implicating disease in the decline of Guam's avifauna. PMID- 1602573 TI - Chemical restraint of Weddell seals (Leptonychotes weddellii) with a combination of tiletamine and zolazepam. AB - A 1:1 combination by weight of tiletamine hydrochloride and zolazepam hydrochloride was administered to 30 adult Weddell seals (Leptonychotes weddellii) in doses varying from 100 to 300 mg. Full immobilization was achieved in 16 seals, moderate sedation in seven and light sedation in seven. Three animals died; two were fully immobilized and one was moderately sedated prior to death. The drug combination was considered satisfactory, although its usefulness was limited by the lack of chemical antagonists when complications were encountered in immobilized animals. PMID- 1602572 TI - Starvation, staphylococcosis, and vitamin A deficiency among mallards overwintering in Saskatchewan. AB - During January to March 1991, 38 mallards (Anas platyrhynchos) found dead from a group of approximately 600 overwintering on the South Saskatchewan River were examined. Thirty birds died from starvation, four had disseminated Staphylococcus aureus infection, and the cause of death of four birds was not determined. All six birds from which the esophagus was examined microscopically, including the four birds with staphylococcosis, had squamous metaplasia of the submucosal glands, a lesion pathognomonic for vitamin A deficiency. Vitamin A deficiency may occur in mallards and other waterfowl that overwinter north of traditional wintering areas and rely on grains deficient in carotenoids. PMID- 1602574 TI - R51163 as a sedative for handling and transporting plains bison and wapiti. AB - Forty captive wapiti (Cervus elaphus) and thirty-two bison (Bison bison bison) were tested in April and October 1988, respectively, for their response to the sedative R51163. Treatment animals were injected with either 0.1, 0.2, or 0.3 mg of R51163/kg and then observed for 72 hr. Behavior was significantly altered by the drug. Hyperactive, aggressive, and milling behavior was characteristic of treated wapiti and they were extremely dangerous and reared when hind quarters were touched. Although treated plains bison displayed some milling behavior, they were generally more calm than wapiti. There was a marked difference between sexes in plains bison for all behavioral categories. Male bison were more ataxic, often observed in sternal or lateral recumbency, less conscious, and were slower to respond than females or controls. Respiratory rate increased in treated wapiti and plains bison, and heart rates of treated wapiti increased. Because of the powerful sedative effect on large, male bison, R51163 may be useful for handling unmanageable or dangerous animals and warrants further studies. PMID- 1602575 TI - Blood chemistry and endoparasites of the mountain hare (Lepus timidus L.) in high and low density populations. AB - In order to study the effect of high population density on the condition, blood characteristics and helminth parasitism of mountain hares (Lepus timidus), 12 specimens were shot in December 1982 and 12 more in February 1983 on the west coast of central Finland (group 1, dense population). In addition 14 hares were shot in December 1982 about 100 km from group 1 (group 2, dense population). Group 3 consists of 15 hares from stable, rather low density populations shot in southern Finland during three previous winters. The hares in group 1 were the lightest, had the least fat and were the most seriously infected with Protostrongylus pulmonalis and Trichostrongylus retortaeformis, while those in group 2 were the heaviest and had the highest Ca, Mg, alkaline phosphatase and creatinine values. The group 3 hares had the most fat. The group 1 animals shot in February 1983 had higher Ca, Mg, triglyceride and cholesterol values than those shot in December 1982. It seems that high population density combined with a lack of suitable food leads to poor condition and high endoparasite abundances. The differences in Ca and Mg are probably due to diet. The higher creatinine values in group 2 and in the hares with little or no T. retortaeformis infection may be due to the greater muscle mass. PMID- 1602576 TI - Blood gas and catecholamine levels in capture stressed desert bighorn sheep. AB - Forty-seven bighorn sheep (Ovis canadensis nelsoni) were captured within a 3-day period in December, 1989 as part of a California Department of Fish and Game effort to repopulate historic ranges in California. They were captured on the Mojave Desert in the Kelso Mountains near Old Dad Peak, San Bernardino County, California. Venous blood gases measured at the site of capture demonstrated a severe metabolic acidosis (base deficit, 23 mEq/liter), with no evidence of respiratory acidosis. There were moderately elevated plasma epinephrine (1.25 ng/ml), norepinephrine (2.60 ng/ml), and dopamine (114 pg/ml) levels. These data appear to reflect animals that have been moderately stressed. These acid-base catecholamine values differ from values in resting domestic sheep, and are similar to those reported in greyhounds after brief strenuous exercise. PMID- 1602577 TI - Hormonal contraception of feral mares with Silastic rods. AB - Homogeneous Silastic rods containing ethinylestradiol (EE) (1.5 or 4 g), estradiol-17 beta (E) (4 g) or progesterone (P) (6 g) were implanted into feral mares (Equus caballus) between 4- and 10-yr-old. Six treatment groups (greater than or equal to 10 mares/group) of non-pregnant mares received 36 g P and 12 g E (P+E), 36 g P and 8 g EE (P+HEE), 1.5 g EE (LEE), 3 g EE (MEE, 8 g EE (HEE) or control-implanted mares (CI). CI received implants containing no steroid. Two groups of pregnant mares received P+HEE or HEE. Stallions were placed with the mares 15 to 26 mo after implanting. Blood was collected biweekly for up to 28 mo after implanting and serum analyzed for P by radioimmunoassay. A single P value greater than or equal to 2.5 ng/ml indicated ovulation and 2 consecutive values greater than or equal to 2.5 ng/ml indicated pregnancy. Serum from blood collected before and at 4, 12, 24, 50, 64 and 89 wk after implanting was analyzed for EE concentrations. All animals pregnant at the time of contraceptive placement delivered normal foals. Contraceptive efficacy for groups LEE, MEE, HEE and P+HEE were 75, 75, 100, and 100%, respectively after two breeding seasons. Suppression of ovulation appeared to be inversely related to the concentration of EE used in the implant. The percent of animals ovulating after 2 yr of contraception in each group was 100, 100, 88, 62, 20, and 12 for groups CI, P+E, LEE, MEE, HEE and P+HEE, respectively. The pregnancy rate for the same groups was 100, 78, 25, 25, 0 and 0%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602578 TI - American wigeon mortality associated with turf application of diazinon AG500. AB - Nine fairways of a golf course located in Bellingham, Washington were treated with diazinon AG500 at a target application rate of 2.2 kg active ingredient (AI) per ha. The chemical application with a "boomless" sprayer resulted in a variable distribution of diazinon residues on the turf (associated with a deep thatch layer) that ranged from 1.0 to 6.2 kg AI/ha. The diazinon-treated turf was irrigated with 1.3 cm of water immediately following application. The post irrigation diazinon residue levels ranged from 100 to 333 ppm (mean = 209; SD = 88; n = 8). These residue levels were higher than expected based on results of turf studies in other regions of the United States. Eighty-five American wigeon (Anas americana) died after grazing on one treated fairway on the day of application following irrigation. The brains of all 85 wigeon were analyzed for acetylcholinesterase (AChE) activity. Wigeon that died on the study area (n = 85) showed 44% to 87% depression of AChE (mean = 76%; SD = 7.1%) when compared to control wigeon (n = 3; AChE Activity = 1.86) AChE levels. Upper GI tract contents of 15 of the 85 dead wigeon contained 0.96 to 18.1 ppm diazinon. Extensive carcass searches revealed no other avian mortality attributable to diazinon toxicity on the treated study area. Although initial post-irrigation diazinon residues in grass samples were higher than expected, diazinon levels in grass samples on day seven post-application had declined to an average of 29 ppm. American wigeon appear to be vulnerable to exposure to diazinon.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602579 TI - Traumatic, degenerative, and developmental lesions in wolves and coyotes from Saskatchewan. AB - A retrospective review was done of traumatic and osseous lesions in 241 wolves (Canis lupus) and 316 coyotes (Canis latrans) necropsied at the University of Saskatchewan between 1971 and 1990. Most lesions were the result of interspecific conflict. The most frequently occurring lesion in wolves was fracture of one or more bones, primarily ribs. Lesions were healed in most cases and appeared to be compatible with injuries caused by prey animals. One wolf, found dead, died as a result of thoracic trauma. Limb and skull fractures were less common. Fractures were uncommon in coyotes. The most frequent injuries in coyotes were related to gunshot wounds. Four coyotes had been killed but not eaten by wolves. One wolf had been killed and another attacked by wolves. Porcupine (Erethizon dorsatum) quills contributed to the death of a wolf and two coyotes. Degenerative joint disease, involving the spinal column and limb joints, was found in a few individuals of both species. A coyote had severe anomalies of the spinal column and a wolf had anomalous external genitalia. PMID- 1602580 TI - Microflora of the pouch of the koala (Phascolarctos cinereus). AB - Microflora of the pouch epithelium of 17 female koalas (Phascolarctos cinereus) were examined in relation to their current reproductive status and recent reproductive history. No microbial growth was observed in pouch swabs from 13 of 17 (76%) koalas, including four females without young, seven with pouch young and two with back young (i.e. permanently emerged from the pouch). Growth of bacteria or yeasts was observed in pouch swabs from four koalas, each of which had experienced mortality of its pouch young during the current breeding season. Seven species of microorganisms were isolated, including Pseudomonas aeruginosa, Serratia marcescens and Enterococcus faecalis. Based on the absence of microflora in the majority of females examined, we propose that the pouch epithelium normally provides a hostile environment for microbial colonization. PMID- 1602581 TI - Isolation of Borrelia burgdorferi from Peromyscus leucopus in Oklahoma. AB - Borrelia burgdorferi was isolated from a field-caught Peromyscus leucopus from central Oklahoma (USA). The strain was identified as B. burgdorferi by reaction with monoclonal antibody H5332 specific for the outer surface protein OspA of B. burgdorferi. This represents the first isolation of B. burgdorferi from a wild mouse outside of the normal range of the known vectors Ixodes dammini and I. pacificus. PMID- 1602582 TI - Chlamydiosis in a red-tailed hawk (Buteo jamaicensis). AB - A red-tailed hawk (Buteo jamaicensis) with signs of respiratory distress and diarrhea was captured in the Manchac Wildlife Management Area, Louisiana (USA) and died the following day. At necropsy, the carcass was emaciated and there were splenomegaly, and fibrinous pericarditis, airsacculitis, and perihepatitis. Microscopically, there were fibrinous pericarditis and airsacculitis, myocardial necrosis, necrotizing hepatitis, splenic necrosis with reticuloendothelial cell hyperplasia, interstitial pneumonia and focal pancreatic necrosis. Intracytoplasmic chlamydial inclusion bodies were noticed in macrophages in the fibrinous exudate covering air sac and pericardium, and in spleen, liver, heart, lung, and pancreas. Schizonts compatible with a Sarcocystis sp.-like protozoon were present in the walls of air capillaries in the lung. A Chlamydia sp.-like organism was isolated in embryonating chicken eggs and cell culture and identified as C. psittaci with immunofluorescent staining. PMID- 1602583 TI - Mycoplasma gallopavonis in eastern wild turkeys. AB - Serum samples and tracheal cultures were collected from eastern wild turkeys (Meleagris gallopavo sylvestris) trapped for relocation in South Carolina (USA) during 1985 to 1990. Sera were tested for Mycoplasma gallisepticum and M. synoviae by the rapid plate agglutination and hemagglutination inhibition tests and were found to be negative. Tracheal cultures were negative for all pathogenic Mycoplasma spp., including M. gallisepticum, M. synoviae, M. meleagridis, and M. iowae. However, M. gallopavonis was isolated from every group of wild turkeys tested in 1986 to 1990. These data suggest that M. gallopavonis, which is generally considered nonpathogenic, may be a common microorganism in eastern wild turkeys. PMID- 1602584 TI - Seasonal reproduction of vampire bats and its relation to seasonality of bovine rabies. AB - Studies of pregnancy and lactation in vampire bats (Desmodus rotundus) in northern Argentina over a 4 yr period showed an inverse relationship between prevalence of pregnancy and lactation, the consequence of birth and onset of lactation, which was correlated with the wet season. The seasonal influx of young susceptibles into the vampire population in the wet season coincided with the well known increase in vampire transmitted rabies in that season. PMID- 1602585 TI - Capripoxvirus disease in an Arabian oryx (Oryx leucoryx) from Saudi Arabia. AB - Lumpy skin disease caused by a capripoxvirus was observed in a captive-bred female Arabian oryx (Oryx leucoryx) at the National Wildlife Research Center, Taif, Saudi Arabia. Clinical signs included severe general depression with fever, anorexia, greater than 1,000 nodular cutaneous lesions and gradual recovery over 2 mo. The virus was found by electron microscopy and paired sera showed an increasing virus neutralization antibody titer against capripoxvirus. A serologic survey of the herd of 90 oryx showed a low prevalence (2%) of this infection. This report describes the first case of lumpy skin disease in an Arabian oryx. PMID- 1602586 TI - An epizootic of malignant catarrhal fever in a large captive herd of white-tailed deer (Odocoileus virginianus). AB - Over a 4-mo period 23 of 28 white-tailed deer kept at a small zoo in New Jersey (USA) died. Clinical signs prior to death were minimal and consisted of depression, central nervous system disorders, and watery diarrhea in a few animals only. Histopathology revealed widespread acute vascular lesions, ranging from modest accumulations of blast-like mononuclear cells and edema in the adventitia through to disruption of the tunica media and thrombosis. These vascular lesions were seen in a variety of organs but were most prominent in lung, heart, liver and intestine. Severe vascular changes were associated with necrosis. Lymphoreticular hyperplasia was evident in the lymphoid tissue of all animals. PMID- 1602587 TI - A search for Parelaphostrongylus andersoni in white-tailed deer from Maine. AB - Longissimus dorsi muscles from 42 white-tailed deer (Odocoileus virginianus) from Maine (USA) were examined for the Parelaphostrongylus andersoni. No adult nematodes were found. Prevalence based on the Poisson approximation of a binomial distribution could have been between 0 and 9% (95% C.I.). However, based on prevalence documented elsewhere (10 to 18%), it is unlikely that P. andersoni occurs in white-tailed deer in central Maine. PMID- 1602588 TI - Gastrointestinal helminths of the cetaceans Phocoena spinipinnis (Burmeister, 1865) and Cephalorhynchus eutropia (Gray, 1846) from the southern coast of Chile. AB - Gastrointestinal helminths of the cetaceans Cephalorhynchus eutropia and Phocoena spinipinnis accidentally entangled in gillnets off the coast of Queule, Chile, were identified from 1989 to 1990. Pseudoterranova sp., Polymorphus (Polymorphus) cetaceum and Synthesium tursionis occurred in both cetaceans. Additionally, Anisakis sp. and Braunina cordiformis were found in C. eutropia, and Anisakis simplex was identified from P. spinipinnis. The species with the highest prevalence and mean intensity of infection in P. spinipinnis and C. eutropia were P. (P.) cetaceum and B. cordiformis, respectively. The diet of both cetaceans consists mainly of fishes. PMID- 1602589 TI - Helminth parasites of wild boar, Sus scrofa, in Iran. AB - Fifty-seven wild boars (Sus scrofa) from protected regions of Iran were examined for helminths. Sixteen species of helminths were collected; there were ten nematodes, one acanthocephalan, two trematodes and three larval cestodes. New host and distribution records were established for all helminths except of Taenia solium cysticerci. Wild boar shared nine of these helminths with domestic pigs, six with ruminants and three with human beings in Iran. Metastrongylus pudendotectus and M. salmi are reported for the first time from Iran. PMID- 1602590 TI - Lymphangiomyomatosis in the Atlantic bottlenose dolphin (Tursiops truncatus). AB - The first case of lymphangiomyomatosis in a marine mammal is reported from a stranded male Atlantic bottlenose dolphin (Tursiops truncatus). This progressive proliferative disease involved the lungs and the mediastinal and probably mesenteric lymph nodes. An extraordinarily low level of testosterone may have been pathologically significant since all reported cases of this disease in humans occur in females. PMID- 1602591 TI - Testicular myxosporidiasis in the flat-backed toad, Bufo maculatus (Amphibia: Bufonidae), from Cameroon, Africa. AB - Macroscopic cysts measuring less than or equal to 860 x 500 microns were found in the testes of a flat-backed toad, Bufo maculatus, collected in Cameroon, West Africa. On histologic examination, the cysts contained numerous spores of a Myxobolus sp. (Myxozoa: Myxobolidae). Spores in fixed tissues measured 9.2 microns long, 8.9 microns wide, and 4.0 microns thick; the range of values for length, width, and thickness were 8.8 to 9.6 microns, 8.6 to 9.4 microns, 3.6 to 4.4 microns, respectively (n = 20). The shape index (length/width) was 1.03, and ranged from 1.00 to 1.09. Pathology was limited to a slight constriction of adjacent seminiferous tubules by the cysts. No host inflammatory response was noted. This myxozoan is distinct from all other members of the genus infecting anurans and is assigned the name Myxobolus bufonis sp. n. PMID- 1602592 TI - Cranial asymmetry in a Dall sheep ram (Ovis dalli dalli). AB - The horns of a 13-yr-old Dall sheep ram (Ovis dalli dalli) from the Sheep Mountain herd in Kluane National Park (Yukon, Canada) had unique characteristics. The right horn was 1,127 mm long, while the left horn was only 861 mm long and compressed and distorted at its base. The reduced growth of the left horn was due to chronic epidermitis and osteomyelitis of the cornual process, which began when the ram was 5 yr of age. PMID- 1602593 TI - Preventive effect of exercise training on recurrent stenosis after percutaneous transluminal coronary angioplasty (PTCA). AB - The purpose of this study is to evaluate whether exercise training for 12 weeks prevents the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA). Symptom-limited treadmill exercise with thallium-201 myocardial single photon emission computed tomography (SPECT) was performed one and 13 weeks after PTCA in 18 patients with exercise training and in 20 patients without. For quantitative analysis, the average count of region of interest in the hypoperfused area on the polar map was calculated. A percentage T1 uptake was determined by dividing average count of the hypoperfused area by that of a normal reference area at an initial image (%IU) and a delayed image (%DU). A percentage redistribution (%RD) was obtained by subtracting %IU from %DU as the parameter of residual ischemia in the hypoperfused area. Total treadmill exercise duration and maximal pressure rate product 13 weeks after PTCA increased significantly (p less than 0.01) in the trained group, whereas there was no significant change in the untrained group. %DU increased significantly (p less than 0.01) in the trained group, whereas there was no significant change in the untrained group. %RD decreased significantly (p less than 0.01) in the trained group, whereas there was no significant changes in the untrained group. The restenosis rates at the third month after PTCA was 17% (3/18) in the trained group and 40% (8/20) in the untrained group. These findings suggest that in patients with coronary artery disease exercise training improves myocardial perfusion by preventing the progression of coronary artery stenosis after PTCA. PMID- 1602594 TI - Time course of pulmonary vascular response to an acutely repetitive pulmonary microembolism in dogs--an analysis using pulmonary vascular impedance. AB - To understand the mechanism leading to progressive pulmonary hypertension, we investigated the time course of vascular response to an acutely repetitive pulmonary microembolism in dogs by using pulmonary vascular impedance. In a normal state, the mean pulmonary arterial pressure (mPAP) was transiently increased by emboli, and the impedance moduli of 0 Hz (= Rin), 1.5 Hz and 3 Hz were slightly increased. A four-element electrical vascular model showed the transient increase in peripheral pulmonary vascular resistance (R2) and inertia, and reduction in compliance (C). In contrast, in a state of a slight pulmonary hypertension, mPAP was continuously increased by the same amount of emboli, and the impedance moduli of both 0 Hz and 3 Hz were significantly increased. By a four-element model, a severe increase in R2 and reduction in C were observed, and these changes continued. Therefore, although the vascular response to pulmonary microembolism basically depends on the degree of mechanical obstruction, this response is thought to be modulated by the responsiveness of pulmonary vessels at that time, which is involved in the alteration in the local characteristics of pulmonary vessels, and/or the recruitment of a new blood flow. PMID- 1602595 TI - Echo/Doppler diagnosis of tetralogy of Fallot, ventricular septal defect, pulmonary valve dysplasia, and hypertrophic cardiomyopathy in WKY/NCrj rats. AB - We examined the hearts of 97 WKY/NCrj rats, a strain which spontaneously develops congenital cardiac malformations, by means of echocardiography with a pulsed Doppler ultrasound, and compared the results with those of 20 WKY/Ta rats and 30 normal Wistar rats. Dissection of these WKY/NCrj rats revealed a ventricular septal defect (VSD) in 20 and pulmonary valve dysplasia (PVD) in 41, both VSD and PVD occurring together in 18. VSD was readily diagnosed in vivo by the jet flow signal derived from the left-to-right shunt near the membranous portion, with a sensitivity of 85% and a specificity of 99%. Ultrasound imaging revealed overriding of the aorta and right ventricular (RV) hypertrophy in 18 of the 20 rats with VSD. Of the 20 rats with VSD, 10 had a systolic high-velocity jet across the RV outflow indicating an infundibular stenosis. PVD was commonly accompanied by a pulmonary regurgitation signal, with severe cases showing intensified echo and low excursion of the cusps. The regurgitation signal showed a good diagnostic value for PVD with a sensitivity of 82% and a specificity of 85%. In the remaining 54 WKY/NCrj rats without VSD or PVD, the ratio of mean left ventricular (LV) wall thickness to cavity dimension, the fractional shortening of the LV dimension, and the septal to LV free wall thickness ratio were all abnormally high, and the motion of the ventricular septum was reduced in most of the cases compared with that of the other two strains. All these features resemble the hypertrophic cardiomyopathy seen in humans, which further promises that the rats should be a useful model for the controversial disease. PMID- 1602596 TI - Compensatory mechanisms and their limitations in heart failure. PMID- 1602597 TI - Norepinephrine disrupts cytoskeletal framework of microtubules in rat hearts. AB - Sympathetic activations may deteriorate myocardial failure due to progression of myocardial cell injury. In the present study, to test whether microtubules, calcium ion (Ca2+) sensitive cytoskeletons, are disrupted by norepinephrine (NE) and whether beta-adrenoceptor antagonist could attenuate the disruption of microtubules, structures of microtubules are studied in rat hearts with continuous subcutaneous infusions of norepinephrine. In the sham operated rats the microtubules stained by immunohistochemical technique showed normal network structures. A low dose of NE infusion (2 micrograms/kg/h) for 6 h resulted in a minimal change in microtubule structures. However, infusion for 24 h of NE (2 micrograms/kg/h) and a large dose of NE infusion (20 micrograms/kg/h) for 6h caused disruptions of microtubules in small patchy lesions (8 +/- 3%, 12 +/- 4% of area, respectively). A large dose of NE infusion for 24 h increased systolic blood pressure from 116 +/- 6 to 152 +/- 4 mmHg and increased plasma NE concentration from 430 +/- 40 to 17100 +/- 3700 pg/ml and further disrupted the network of microtubules in 40 +/- 6% of the total area. Propranolol (500 micrograms/kg/h) markedly attenuated NE-induced disruptions of microtubules. Disruptions of microtubules may be one of the underlying mechanism of deterioration of myocardial failure in chronic heart failure in which sympathetic activity is markedly activated. PMID- 1602598 TI - The distribution of the blood flow during exercise in chronic heart failure- compensatory mechanism to the decreased cardiac output. AB - To evaluate the blood flow distribution during exercise, 51 patients with chronic heart failure underwent ergometer exercise testing measuring cardiac output and leg blood flow. At the given workrate (10 watts and 25 watts) cardiac index (L/min/m2) was significantly lower in NYHA class III patients than class I patients (at 10 watts, 4.08 +/- 1.05 in class I, 4.01 +/- 1.29 in class II and 3.00 +/- 0.89 in class III, p less than 0.05; I vs III), while leg blood flow (L/min/m2) was similar among 3 groups (at 10 watts, 1.19 +/- 0.32, 1.29 +/- 0.25 and 1.16 +/- 0.29, ns). Consequently, residual blood flow (L/min/m2) was significantly lower in class III than class I (at 10 watts, 2.89 +/- .92 and 2.78 +/- 1.27 and 1.84 +/- 0.71, p less than 0.05: I vs III). The results at 25 watts were similar. Serum noradrenaline was significantly higher in class III patients than class I patients at both 10 and 25 watts. We concluded that in severe heart failure, agreater blood flow is distributed to the working leg muscle as compared with less severe heart failure. And such an increased distribution of blood flow to working leg plays a role to compensate an insufficient cardiac output response in patients with severe heart failure. PMID- 1602599 TI - Changes in oxygen uptake-work rate relationship as a compensatory mechanism in patients with heart failure. AB - To assess the compensatory change in oxygen uptake (VO2) kinetics during exercise in patients with heart failure, we performed cardiopulmonary exercise testing using a cycle ergometer in 29 cardiac patients and 18 normal subjects. The work rate increased linearly (1w/6sec) after a 4 min, 20w warm-up. The ratio of increase in VO2 to increase in work rate (delta VO2/delta WR) was determined by linear regression of VO2 plots. Cardiac output by dye dilution method and plasma norepinephrine concentration (NE) were measured at rest and 20w warm-up. VO2 at rest and at 20w warm-up and delta VO2/delta WR decreased significantly with increasing severity in NYHA functional classification. delta VO2/delta WR showed significant negative correlation to the difference in NE levels at rest and at 20w (r = -0.69, p less than 0.001). The delta values of arteriovenous O2 content difference, calculated using Fick's principle, and cardiac index from rest to 20w warm-up failed to show significant relationship to delta VO2/delta WR. These results suggest that the decrease in VO2 requirement in heart failure patients is due probably to blood redistribution during exercise as a compensatory mechanism for exercise intolerance. PMID- 1602600 TI - Role of left atrial booster pump function in a worsening course of congestive heart failure. AB - We evaluated changes in left ventricular (LV) preload and the Doppler-derived transmitral late to early diastolic peak velocity ratio (A/E ratio) during the exercise in 27 patients with ischemic heart disease. After the exercise, A/E ratio decreased in 16 patients with a remarkable elevation in LV preload, and increased in 11 with a mild elevation. Further, Doppler transmitral flow in conjunction with pulmonary venous flow and hemodynamic parameters were analyzed in 11 dogs during a worsening course of heart failure induced by dextran infusion. The relationship of A/E ratio to LV end-diastolic pressure showed a quadratic curve concave to the pressure axis. A/E ratio, an index expressing left atrial (LA) contribution to LV filling, returned to that seen before volume loading under the condition of cardiac dysfunction. Pulmonary venous reflux fraction determined as the ratio of peak velocity of pulmonary venous reflux during LA systole to the sum of systolic and diastolic peak velocities of pulmonary venous antegrade flow, did not increase here. In this situation, blood could not be ejected from the left atrium into the left ventricle and even into the pulmonary veins during LA contraction. Finally, LV filling was not compensated by the left atrium, and LA booster pump function itself was deteriorated. PMID- 1602601 TI - Effects of secondary organ failure on compensation of acute heart failure in patients with myocardial infarct and dilated cardiomyopathy. AB - Compensation for heart failure can be influenced by cardiac loads due to organ failure. This investigation studied the effect of secondary organ failure on the hemodynamics of acute heart failure. Of 106 patients with acute heart failure due to myocardial infarction or dilated cardiomyopathy, 49 (46%) patients had secondary organ failure, either kidney, liver, brain or blood. Their acute heart failure was sustained for significantly longer than that of 57 patients without organ failure. A transient but severe decompensation induced secondary organ failure, although the left ventricular ejection fraction was not different from that of the control without heart failure. Hypervolemia in cases of renal failure, bradycardia in loss of consciousness, hyperdynamic state in anemia and low blood pressure in liver dysfunction caused the sustained acute heart failure. These results suggested that secondary organ failure might occur in 46% of patients with acute heart failure, and might disrupt compensation by different kinds of hemodynamic loads in low cardiac function. PMID- 1602602 TI - [Monitoring of cyclosporin A concentration in whole blood with fluorescence polarization immunoassay after bone marrow transplantation]. AB - Cyclosporin A, a strong immunosuppressive agent, has been used to prevent rejection or graft-versus-host disease (GVHD) after organ transplantations including bone marrow transplantations. Monitoring of cyclosporin A concentration in whole blood is necessary for its high frequency of side effects. The authors to measured its concentration by means of radioimmunoassay (RIA) as well as fluorescence polarization Immunoassay (FPIA) a cases after bone marrow transplantation. There was a good correlation between these two methods. FPIA is less specific for cyclosporin A than RIA, but it is an easier method. It is important to measure the concentration of cyclosporin with FPIA because there are metabolites of cyclosporin A which cannot be measured with RIA. Thus FPIA can be applied to the routine monitoring of cyclosporin. PMID- 1602603 TI - [Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in blood diseases]. AB - In patients with malignant blood disease, infection is the most serious complication. The prompt differential diagnosis of tuberculosis leads to an appropriate treatment. A method based on DNA amplification and hybridization for the rapid detection of Mycobacterium tuberculosis was used to test 10 clinical specimens (sputum, gastric aspirate and pleural effusion) from blood disease patients in whom tuberculosis was suspected. Mycobacterium tuberculosis DNA was detected in 3 specimens, including one which was negative on standard microbiological criteria (microscopy and/or culture). The other 7 specimens with fever or abnormal shadow on a chest X-ray were negative by both our method and the Standard microbiological criteria. Rapid diagnosis of tuberculosis by amplification of mycobacterial DNA in cases of blood disease in clinically useful. PMID- 1602604 TI - [Magnetic resonance imaging of the bone marrow in patients with aplastic anemia and myelodysplastic syndrome]. AB - Magnetic resonance imaging (MRI) of bone marrow was performed in 16 patients with aplastic anemia (AA) and myelodysplastic syndrome (MDS). Sagittal images from the lower thoracic and lumbar vertebral marrow were evaluated on short TI IR sequences (STIR, IR 2000/160/20). Four distinct patterns of signal intensity (SI) of the STIR images corresponding with active red marrow were classified as follows: pattern I, homogeneously low SI (4 cases); II, marginally high SI (2 cases); III, heterogeneously high SI (8 cases); IV, homogeneously high SI (2 cases). The SI distribution of STIR images strongly correlated with the cellularity of clot specimens of aspirates from sternum using the Wiebel test plate. In all three patients with AA, the STIR images revealed pattern I. In 8 of 13 cases of MDS patients, the STIR images were classified into pattern III. In one patient with hypoplastic MDS, the STIR image showed low SI. The STIR images of two AA patients at clinical remission after treatment showed marginally high SI similar to those of normal marrow. MRI of bone marrow can be a useful technique for the diagnosis of AA and MDS and for monitoring therapeutic effects. PMID- 1602605 TI - [Flow cytometric analysis of platelets in patients with variant thrombasthenia]. AB - Three cases of suspected variant thrombasthenia patients (out of 10 cases of Glanzmann's thrombasthenia), who had significant amounts of platelet GPIIbIIIa, underwent flow cytometry to analyse the binding capacity of monoclonal antibodies against GPIIbIIIa to platelets. The monoclonal antibodies used in this study were as follows: PLT-1 and AP-2 recognizing the IIbIIIa complex; TP 80, P2 and AP-4 recognizing IIb:;AP-5 recognizing IIIa;OP-G2, which binds an epitope near the RGD binding site and 3F11. OP-G2 also recognizes conformational changes of activated platelets by increased binding. Case 1 platelets showed a binding capacity of 28 63% of that of normal platelets for TP80, AP-2, AP-4, and 3F11, but no binding to OP-G2. Case 2 platelets also showed 16-44% binding with TP80, AP-2, AP-4, AP-5, and 3F11, but no binding to OP-G2. These findings indicated the presence of structural abnormalities of the functional site of platelet GPIIbIIIa in cases 1 and 2. Case 3 platelets bound with all monoclonal antibodies normally, but normal increase in the binding of OP-G2 to platelets activated by thrombin or ADP was not seen, indicating a lack of activation of the fibrinogen binding site of platelet GPIIbIIIa. PMID- 1602606 TI - [Molecular analysis of bcr/abl mRNA in chronic myelogenous leukemia after bone marrow transplantation by using RT-PCR method]. AB - Thirty three patients with chronic myelogenous leukemia (CML) treated by allogeneic bone marrow transplantation (BMT) were evaluated for bcr/abl mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR). The bcr/abl mRNA was detected in 22 out of 33 patients in clinical complete remission after BMT. The bcr/abl mRNA was present only transiently in 6 patients. It was speculated that leukemia cells were not eradicated by conditioning therapy of BMT, but patients maintained clinical complete remission due to GVL (graft versus leukemia) effect. Further study is necessary to estimate the clinical value of this technique to predict the outcome in CML patients. PMID- 1602607 TI - [A successful allogeneic bone marrow transplantation for acute promyelocytic leukemia with anthracycline-induced cardiomyopathy at relapse]. AB - A 14-year-old girl with acute promyelocytic leukemia (APL) developed cardiomyopathy following chemotherapy for remission induction and subsequent consolidation consisting of cumulative doses of 644 mg/m2 of daunorubicin and 31 mg/m2 of mitoxantrone. Six months after the first complete remission, when relapse of APL was recognized an allogeneic bone marrow transplantation (BMT) from her HLA-identical brother was performed. A preconditioning regimen, consisting of cytarabine (Ara-C, 2 g/m2/day x 3 days and 4 g/m2/day x 3 days), total body irradiation (TBI, 1200 cGy) and etoposide (VP-16, 50 mg/kg) caused moderate gastrointestinal symptoms and transient hemorrhagic cystitis, but did not worsen her cardiac function. Both continuous intravenous administration of heparin to control DIC and continuous low dose dopamine infusion to prevent cardiac failure achieved their purpose. The patient is leukemia-free and has no symptoms related to cardiomyopathy at the eight month after BMT. A preconditioning regimen (Ara-C, TBI and VP-16) appeared to be suitable for BMT to a patient with anthracycline-induced cardiomyopathy. PMID- 1602608 TI - [Efficacy of leukocyte-depleted platelet concentrates for prevention of HLA alloimmunization in patients with frequent platelet transfusions: a prospective multi-institutional study using a polyester platelet filter]. AB - A prospective multi-institutional study was conducted to assess the efficacy of leukocyte-depleted platelet concentrates, prepared by a method using a newly developed polyester filter, in the prevention of HLA-alloimmunization in patients with hematological disorders. Patients who were expected frequent platelet transfusions, were assigned into two groups, receiving either standard platelet concentrates (control group) or leukocyte-depleted platelet concentrates prepared through a polyester platelet filter, Sepacell-PL (filtered group). All patients received leukocyte-depleted red cell products. Of III patients enrolled, 72 were evaluable, 23 in the control and 49 in the filtered group. Both groups were comparable according to age, sex ratio, underlying disorders, previous exposure to alloantigens by transfusion and/or pregnancy. There was no statistically significant difference in the number and duration of transfusion in the two groups. There were significant differences in HLA-alloimmunization rate (9 cases out of 23, 39% in the control group versus 4 cases out of 49, 8% in the filtered group; p less than 0.01) and refractoriness to platelet transfusion from random donors (6 cases out of 23, 26% in the control group versus 2 cases out of 49, 4% in the filtered group; p less than 0.05). These results indicated that leukocyte depleted platelet concentrates prepared through the polyester platelet filter are beneficial to reduce HLA-alloimmunization in patients with frequent platelet transfusions. PMID- 1602609 TI - [Atypical leukemia accompanied by vitamin B12 deficiency]. AB - A 76 year old female with atypical leukemia complicated by vitamin B12 deficiency demonstrated marked fluctuation in blast percentage and hemopoiesis over 8 month period. She underwent surgical removal of pancreas head cancer 5.5 years ago. In January 1989 severe pancytopenia and mild increase of bone marrow blast were found. Blood transfusions and inadvertent administration of Vitamin B12 resulted in alleviation of pancytopenia and decrease in blast percentage. Several months later her bone marrow blast exceeded 30%, when serum B12 concentration was below 90 pg/ml. B12 injection and blood transfusion resulted in significant improvement in her hematological condition, but shortly thereafter she died of fulminant hepatitis. Her bone marrow cells showed a polyclonal constitution, as assessed by the RFLP-methylation technique using the PGK gene as a probe. The coexistence of leukemic- and normal clones under Vitamin B12 deficiency conditions and the differing behavior of such clones to B12 supplementation may explain the unusual clinical course observed in this patient. PMID- 1602611 TI - [Five cases of hematological disorders associated with acute myocardial infarction in thrombocytopenia]. AB - Case of hematological disorders associated with acute myocardial infarction had been found in five of forty five autopsy cases which had hematological disorders during the past seven years. The five cases of hematological disorders consisted of two cases of myelodysplastic syndrome, a case of aplastic anemia, a case of primary myelofibrosis in blast transformation, and a case of acute myelogenous leukemia. All the patients were over 60 years old. Four patients had coronary artery stenosis and extensive myocardial infarction. Fibrinogen degradation products were elevated in four patients. DIC was recognized in two and suspected in two others. In all cases, platelet counts markedly decreased to less than 2.5 x 10(10)/L. Since no chest pain was noted by any patient, it was difficult to diagnose acute myocardial infarction without autopsy, except in one case. It is important to recognize the possibility of severe cardiac dysfunction due to myocardial infarction in thrombocytopenia, especially in the aged with DIC. PMID- 1602610 TI - [A case report of AML M0:CD7, 33 (+) AML M0 case initially presented with cervical lymphadenopathy]. AB - A 59-year-old man was admitted because of generalized lymphadenopathy with fever and vomiting. His peripheral blood showed leukocytosis with a WBC of 93,500/microliters, and the bone marrow picture revealed a predominance of blast cells. The blasts were negative for peroxidase, alpha-naphthyl butyrate esterase and PAS, and had the phenotype of CD 7, 13 and 33 positive. A diagnosis of AML M0 was made, based on the criteria of the NCI-sponsored workshop in 1988. His initial status had been compromised by acute renal failure which necessitated hemodialysis. He responded partially to chemotherapy consisting of daunorubicin, cytarabine and prednisolone. However leukemia recurred and the patient suffered from various episodes of infection and died six months after admission. The Southern blotting showed the germ line configuration for TCR-beta chain and immunoglobulin heavy chain genes. No messenger RNA was detected for myeloperoxidase, c-myc and c-jun, while c-fms, c-fos and c-myb were expressed on Northern blotting. It is intriguing to detect c-fms and c-fos expression in these poorly differentiated leukemic cells. PMID- 1602612 TI - [Munchhausen syndrome with severe iron deficiency anemia]. AB - A patient with Munchhausen syndrome who had severe iron deficiency anemia (IDA) is reported. A 31 year-old female presented with irregular genital bleeding. However, gynecological examination disclosed no evidence of specific disorders causing bleeding. Tests for bleeding tendency and hemolysis were all negative. Although massive bleeding was absent, she had three episodes of a rapid fall in Hb level associated with marked fatigue and weakness, and subsequently rapidly developed serious IDA afterwards. Factitious bleeding was strongly suspected. Blood transfusion performed when the patient was not being watched failed to increase Hb, while transfusions given while the patient was watched were effective. She was not cooperative throughout the hospital course and was discharged on her own request. In outpatient clinic, the diagnosis was confirmed by the evidence that she diluted her own blood samples. PMID- 1602613 TI - [Successful low-dose etoposide therapy for a case of myelofibrosis with chronic myelogenous leukemia megakaryocytic predominance type]. AB - A 38-year-old woman presented with ear pain and vertigo. No hepatosplenomegaly or lymphadenopathy were found, but her platelet counts markedly rose to 414 x 10(4)/microliters with an increase of megakaryocytes in the bone marrow (859/microliters). Cytogenetic assay revealed positive Ph1 chromosome and rearrangement of the break point cluster region (bcr). Although platelet counts remained under 100 x 10(4)/microliters after the administration of carboquone, a high fever and pancytopenia appeared 31 months later. Bone marrow biopsy showed marked myelofibrosis which was improved by low dose etoposide. This case was thought to be Ph1 positive ET, but it was more compatible with CML megakaryocytic predominance type according to the newly proposed "Hannover criteria for myeloproliferative disorders" and cytogenetic assay. PMID- 1602614 TI - [Acute myelogenous leukemia transformed from myelodysplastic syndrome with tetraploid chromosome constitution]. AB - A 57-year-old female presented with general fatigue. She had neither lymphadenopathy nor hepatosplenomegaly. Laboratory data revealed anemia and leukopenia (1,500/microliters) with a differential count of 4.5% leukemic cells. The myelogram revealed 34.4% leukemic cells, of which diameter ranged from 20 to 28 microns. The diagnosis was acute myelogenous leukemia (FAB: M2) with myelodysplasia. Cytogenetic analysis revealed that the leukemic cells had chromosome abnormalities involving both diploidy and tetraploidy with structural rearrangement. Structural rearrangement included del(5) (q22q33), del(15) (q22q24), and t(3; 12) (q25;p13). Small dose aclacinomycin-A treatment was effective in reducing the number of leukemic cells in bone marrow, and both anemia and leukocytopenia were improved. PMID- 1602615 TI - [Megakaryoblastic transformation associated with disseminated intravascular coagulation in the course of polycythemia vera: a case report]. AB - A 57-year-old male who had suffered from polycythemia vera (PV) and had been treated with pipobroman, carbazilquinon and busulfan for ten years presented with fever. CBC revealed anemia and thrombocytopenia without an increase of leukemic blasts (WBC, 7,700/microliters, RBC 294 x 10(4)/microliters, Hb 9.1 g/dl, Plt 1.5 x 10(4)/microliters). Bone marrow aspiration resulted in dry tap. Bone marrow biopsy showed hyperplastic marrow with fibrosis and no increase in leukemic blasts. Eleven days later the patient became leukemic and he died of DIC. Blast cells showed a high nucleo-cytoplasmic ratio, basophilic cytoplasm and cytoplasmic blebs. Cytochemical and immunophenotype analysis of the blast cells showed the following results; myeloperoxidase (-), chloroacetate esterase (-), Sudan black (-), acid phosphatase (+), acetate esterase (+), PAS (+), HLA-DR (+) and GPIIb/IIIa (+). Platelet peroxidase reaction on electron microscopy was positive in perinuclear spaces and endoplasmic reticulum. A diagnosis of megakaryoblastic transformation of PV was made. Although acute myelogenous leukemia has been shown to develop occasionally in the course of PV, acute megakaryoblastic leukemia with DIC following PV is a very rare condition. PMID- 1602616 TI - [Lymphomatoid granulomatosis (LYG) occurring in a patient with follicular lymphoma during remission]. AB - A 49 years-old man presented with dry cough, low grade fever, and abnormal shadow on a chest X-ray. He had suffered from follicular lymphoma of the liver 5 years previously. He received irradiation therapy in combination with chemotherapy for approximately three years and had been in complete remission. Physical and radiological examination revealed pleural effusion and softly dense masses in the right lung. The laboratory data were within normal limits. He was diagnosed as having lymphomatoid granulomatosis (LYG) by open lung biopsy. The lung lesion was mainly infiltrated with T cells. The patient received prednisolone and the lung lesions disappeared. However, when a lung mass was noted two months later, he started to receive combination chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisolone every three months. He has not shown relapse of LYG so far. To investigate the association between the preceding follicular lymphoma and subsequent LYG at this time, DNA analysis using the PCR technique was carried out. The LYG lesion did not show a rearranged band for the JH probe, while the paraffin-embedded specimen of the preceding follicular lymphoma had shown rearranged band for the JH band. Southern blot analysis of the LYG lesion, showed no rearrangement for TCR beta, gamma or JH probe. These findings indicate that the LYG was different from the preceding follicular lymphoma in terms of origin. LYG is considered to be induced in the immunosuppressive state due to lymphoma. PMID- 1602617 TI - [Acute lymphocytic leukemia (L1) preceded by hypercalcemia]. AB - A 37-year-old female with hypercalcemia presented with lumbago, nausea and vomiting. Peripheral blood (PB) and bone marrow (BM) smears revealed no lymphoblasts on the first admission. The value of parathyroid hormone related protein (PTHrP) was increased and osteoporosis was found in the lumbar vertebrae. After 5 months, diagnosis of acute lymphocytic leukemia (ALL) was made on the evidence that lymphoblasts were found in PB (1%) and in BM (98%). Treatment with vincristine, daunorubicin, prednisolone and L-asparaginase achieved complete remission (CR) and the serum calcium level returned to the normal range. She has maintained CR, and is currently treated with consolidation therapy by cyclophosphamide and methotrexate. Acute leukemia is known to be rarely accompanied with hypercalcemia. This rare case was accompanied with hypercalcemia in acute leukemia. Hypercalcemia appeared to be attributable to the increased bone absorption by PTHrP derived from tumor cells. This important case will help understanding the etiology of hypercalcemia associated with ALL. PMID- 1602618 TI - [Essential thrombocythemia that transformed to myelofibrosis after three years]. AB - A 66-year-old man was presented with thrombocytosis in February, 1988. Laboratory examinations on admission revealed a white blood cell count of 17,700/microliters and a platelet count of 274.4 x 10(4)/microliters. Bone marrow aspirates showed an increase of megakaryocytes (1,294/microliters). There was no fibrosis or Ph1 chromosome. He was diagnosed as having essential thrombocythemia and was treated with thrombopheresis, carboquone and ranimustine (MCNU). Subsequently his platelet count was well controlled approximately for three years. He was readmitted because of pyrexia and left hypochondralgia in February 1991. Physical examination revealed hepatosplenomegaly. Peripheral blood revealed leukoerythroblastosis associated with the occurrence of tear drop cells. Bone marrow aspiration resulted in a dry tap and the biopsy specimen showed reticulin fibrosis. This is a fairly rare case of essential thrombocythemia that transformed to myelofibrosis. PMID- 1602619 TI - [Two cases of unclassified chronic myeloproliferative disorders]. AB - Two cases of unclassified chronic myeloproliferative disorders (UCMPD), diagnosed by hematological, cytogenetic and DNA analyses, are described. Case 1: a 63 year old female was admitted because of leukocytosis (96,800/microliters) and splenomegaly. Hematological examinations revealed an increase of the granulocytes in the peripheral blood and bone marrow. The neutrophil alkaline phosphatase (NAP) score was 121. The patient developed blast crisis after 12 months of the chronic phase. Case 2: a 48 year old male was presented with fever and leukocytosis (20,000/microliters). Hematological examinations revealed an increase of granulocytes in the peripheral blood and bone marrow. The NAP score was 33. Maturation-arrest in granulocytic series and morphological abnormalities of marrow cells were not observed in the two cases. Cytogenetic analysis of bone marrow cells disclosed 46, XX, i (17 q) in case 1 and 47, XY, +8 in case 2. Southern blot analysis using 3' bcr probe and TransProbe-1 showed no bcr rearrangement. These cases are thought to be valuable in order to clarify the relationship between UCMPD and CMPD such as Ph1 negative chronic myelocytic leukemia and myelodysplastic syndromes. PMID- 1602620 TI - [Sick sinus syndrome caused by amyloidosis associated with multiple myeloma]. AB - A 65-year-old man, who had been treated for multiple myeloma (MM) since 1986, was admitted because of loss of consciousness in September 1989. An electrocardiogram taken just before admission showed a sinus arrest, junctional escaped rhythm, and marked bradycardia. The diagnosis of sick sinus syndrome (SSS) was made. Soon a temporary pacemaker was inserted, and the dyspnea ameliorated. However on the second day in the hospital, he had a high fever and Staphylococcus aureus was detected in the cultured blood. A diagnosis of septicemia was made, and the pacemaker was removed. He was then treated with beta-stimulants, but died in November 1989. Necropsy revealed cardiomegaly and microscopic examination showed amyloid deposits in the sinoatrial node, and the walls of the ventricles and coronary arteries. Although amyloidosis is often a complication of MM and the heart is frequently affected, SSS caused by amyloidosis associated with MM is quite unusual. In such patients, the use of a pacemaker is controversial, because amyloid deposits are occasionally accelerated by insertion of a pacemaker and for patients with hematological disorders, septicemia associated with pacemaker insertion may prove fatal. PMID- 1602621 TI - [Burkitt's lymphoma with granulocytosis and a high level of C-reactive protein]. AB - A case of Burkitt's lymphoma with granulocytosis including immature cells and a high level of C-reactive protein (CRP) is reported. The activity of interleukin-1 alpha (IL-1 alpha) was detected in the sera, although its activity was not detected in the supernate of the cultured lymphoblasts. The lymphoblasts stimulated production of IL-1 alpha from human umbilical endothelial cells. Therefore, the lymphoblasts infiltrating bone marrow may have stimulated production of IL-1 alpha from bone marrow stroma cells, and IL-1 alpha may have induced granulocytosis and a high level of CRP. PMID- 1602623 TI - [Regional meetings of local subsections of the Japanese Society of Gastroenterology. Abstracts]. PMID- 1602622 TI - [Markedly elevated serum neopterin levels in patients with hemophagocytic histiocytosis]. AB - The authors measured serum neopterin by HPLC in 3 patients with hemophagocytic histiocytosis (HH) with DIC which occurred during the clinical course of T cell malignant lymphoma (T-ML). Extremely high levels of serum neopterin (754.3 +/- SD 467.3 pmol/ml) were found in the patients, about 200, 13 and 10 times higher than that of normal subjects, non-HH DIC patients and non-HH/DIC T-ML patients. Moreover their serum soluble interleukin-2 receptor levels were markedly elevated. These results indicate that markedly raised serum neopterin would be a sensitive parameter for activation of the mononuclear phagocyte system closely associated with T-cell activation and may serve as a useful diagnostic marker for HH. PMID- 1602624 TI - [The 62nd general meeting of the Japanese Society for Hygiene, Matsuyama, March 25-27, 1992. Abstracts]. PMID- 1602625 TI - [Workload in software development work. A consideration based on work characteristics and analysis on workload factors of each working group]. AB - To clarify workload factors in software developing work, we designed questionnaires composed of questions of work-content based on the interview survey. For the analysis of workload, Cumulative Fatigue Symptom Index (CFSI) and the stress-rating-method by 7-likert-scale were used. With the cooperation of the Japanese Software Engineers' Association (SEA) responses were obtained from 270 out of 1,100 members and from 553 non-member software engineers in 18 companies in Japan. The CFSI score obtained was higher than those of other groups of other industries obtained in our previous studies. The stress-rating showed that "time pressure," "too much amount of work, and "ambiguity in job specification" were the highest stressors. The work groups were categorized by the results of CFSI profile into 4 types. The results of stress-ratings were significantly different between the 4 type groups. Based on the multiple comparison analysis, the workload factors of each group could be specified. Out of the foregoing 4 types, the work groups which showed the deviation in F1B (depression) in CFSI and the work groups which showed high scores in every category in CFSI were higher in "ambiguity of specification" in stress-ratings. This result indicates that "ambiguity in specification" is a significant stressor in software engineers. This stressor is caused by the complicated communication process between users and engineers and by the shortage of tools or rules in this process. This stressor is considered to be the most typical workload which characterizes the software developing work. PMID- 1602626 TI - [Amounts of urinary metabolites of p-chloroaniline and their half lives in a patient with acute poisoning]. AB - The aim of this study was to elucidate the time courses of amounts of urinary p chloroaniline (p-CA) metabolites during acute poisoning and to establish a suitable method for biological monitoring of exposure to p-CA. Urinary p-CA metabolites which were previously identified in a patient with acute p-CA poisoning were determined quantitatively over time during admission of a patient by high-performance liquid chromatography (HPLC) and by the colorimetric method of diazo-positive metabolites (DPM). The data of urinary excretion of each p-CA metabolite were fitted to two-compartment model of pharmacokinetics. Major urinary metabolites of p-CA were conjugated p-CA and conjugated 2-amino-5 chlorophenol (2-A-5-CP), and the detected amounts of 2,4-dichloroaniline (2,4 DCA) and free p-CA were small. During the rapid phase for the disappearance of each metabolite, half lives of p-CA, 2-A-5-CP and 2,4-DCA were 2.4, 1.7 and 1.7 h, respectively, and during the slow phase, they were 4.5, 3.3 and 3.8 h, respectively. Urinary p-CA occupied about 62% of the total metabolites detected in the urine, 2-A-5-CP about 36%, and 2,4-DCA about 1%. 2-A-5-CP and p-CA were detected in the urine of the patient obtained on days 3 and 4, respectively, after the poisoning, but the amount of DPM after the second day of the poisoning was in the range of that of non-exposed persons.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602627 TI - Factor structure of self-rating depression scale by Zung and prevalence of depressive state of night shift workers. AB - The Zung self-rating depression scale (SDS) was applied to Japanese night shift workers of a railway company in order to assess the prevalence of depressive state and clarify the structural characteristics of the SDS questionnaire. Out of 2,394 employees, 1,931 male workers were engaged in night shift work and 1,274 men (66.0%) completely answered the questionnaire. The control group was selected from daytime workers. The average age of the subjects was 39.4. Cronbach's alpha coefficient of the night shift workers was 0.835 and that of the control was 0.848. SDS index decreased with age. The mild, moderate, and severe depressive state of night shift workers evaluated by SDS were 13.7%, 2.1%, and 0.6%, respectively. A two-way analysis of variance on SDS index examined age and shift work. Age influenced SDS index, but there was no interaction between the factors. Two factors were extracted by factor analysis. Factor 1 consisted of 8 positive items, accounting for 16.7%. Factor 2 consisted of 8 depressive items, accounting for 15.6%. The residual four items consisted of somatic or behavioral features. Mean value of SDS index by age, distribution of SDS index, and factor structure of SDS questions of the night shift workers were similar to those of the control group. PMID- 1602628 TI - [Content of benzo[a]pyrene residue in the human lung]. PMID- 1602629 TI - Effects of glass fiber exposure on rat lungs. PMID- 1602630 TI - [Nondestructive synchrotron radiation X-ray fluorescence imaging of trace elements in human kidney (I)]. PMID- 1602631 TI - [Present condition on how to select organic solvents on checkup]. PMID- 1602632 TI - [Maximum limits of sleep deprivation time estimated by continuous polygraphic recordings: from two cases of 72 h sleep deprivation]. PMID- 1602633 TI - A newly developed device to measure objective amplitude of accommodation and pupillary response in both binocular and natural viewing conditions. PMID- 1602634 TI - [Two cases of occupational asthma probably caused by pyromellitic anhydride]. PMID- 1602635 TI - [Implementation rate of periodic health checkup at manufacturing factories in Kawasaki]. AB - A questionnaire survey on periodic health checkup was conducted on 4,432 manufacturing factories in Kawasaki and the following results were obtained. 1) Implementation rate of periodic health checkup was 100% in factories with 100 workers or more. In smaller factories employing less than 100 workers, the implementation rate decreased with decrease in their total work force. The rate was 47.5% and 37.7% in factories with 9-4 and 3-1 workers, respectively. 2) The proportion of workers less than 30 years of age decreased and that of 60 or more years of age increased with decreasing size of the total work force. Distribution of both age groups was 12.6% and 12.9%, respectively in factories with less than 10 workers. The proportion of female workers increased from about 10% in factories with 300 workers or more to 26.8% in factories with less than 10 workers. 3) In large factories with 500 workers or more periodic health checkups were implemented mostly at their own or related medical facilities and in factories with 499-10 workers, almost 50% were implemented in independent health service facilities. In factories with less than 10 workers periodic health checkup were implemented mainly at health centers (33.1%) and at hospitals or clinics (26.9%). 4) The main reasons why small factories could not implement periodic health checkup were: (1) they could not afford the time for the implementation (50.0%) and (2) ignorance of the law of mandatory periodic health checkup for workers (23.6%). PMID- 1602636 TI - [A review on assessment techniques for workers' physical and mental conditions by physiological measurements]. AB - It was only a several decades ago that physiological measurements were recognized as effective indicators of human physical and mental conditions in occupational health or ergonomics. The recent rapid progress in sensor and signal processing techniques, however, made these available for practical evaluation techniques. This paper is an overview of the accumulated techniques in several fields including experimental psychology, physiology, medical sciences, and ergonomics. The major topics described herein are as follows: 1) properties and merits of physiological measurements compared with the other techniques, 2) applicability of various physiological indicators evaluated from noninvasive, ambulatory and continuous monitoring techniques, 3) practical physiological measurements and signal processing systems which can be applied at actual workplaces and environment, 4) effective and useful evaluation techniques of physiological indicators such as ECG, blood pressure, respiratory parameters, EEG, EBP, EMG, body movements, body temperature, perspiration, eye movements, CFF and electrodermal activities. Our review of 235 published papers has shown that physiological measurements have made a significant contribution to the assessment of physical and mental workload, CNS (central nervous system) activity level and work performance. However, further studies should be made on detail mechanisms and individual variations. PMID- 1602637 TI - [Phase 3 study of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid, a myocardial imaging agent for evaluating fatty acid metabolism--a multi-center trial]. AB - A multi-center trial of beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I BMIPP) was performed to assess its clinical usefulness in the evaluation of myocardial fatty acid metabolism in 587 patients with various heart diseases. 123I-BMIPP showed relatively decreased uptake compared with 201Tl in the myocardial lesions of 62% of patients with ischemic heart disease (IHD), 39% of those with cardiomyopathy and 32% of those with other heart diseases. In case of myocardial infarction, less uptake of 123I-BMIPP (Type B) than 201Tl was more frequently seen in patients with successful recanalization than in those without recanalization. The patients with matched distribution of the two tracers (Type E) increased in the direct proportion to the interval between the onset of myocardial infarction and the radionuclide studies. The uptake of 123I-BMIPP correlated well with myocardial viability evaluated by 201Tl exercise redistribution studies. Type B was frequently seen in the areas with 201Tl redistribution, while Type E was seen in the fixed defect areas. In the other heart diseases studied, Type E was observed in approximately 60% of patients with dilated or secondary cardiomyopathies. Type B was seen in about 45% of patients with valvular heart diseases and myocarditis. Various types of mismatch between the two tracers were demonstrated in hypertrophic cardiomyopathy and hypertensive heart disease. It is concluded that 123I-BMIPP is a safe and useful agent for the diagnosis of various heart diseases, since it reflects myocardial fatty acid metabolism. PMID- 1602638 TI - [Myocardial perfusion in patients with left bundle branch block and without coronary artery disease]. AB - For the evaluation of myocardial perfusion in patients with left bundle branch block (LBBB), we performed exercise stress (Ex)-redistribution (RD) myocardial tomography with thallium-201 (201Tl) in 23 patients with LBBB and without coronary artery disease (CAD). Myocardial images in patients with LBBB were compared with those of 9 patients with CAD who showed Ex induced transient septal defect. Bull'-eye maps (201Tl distribution maps at Ex and RD and 201Tl washout rate [WOR] map) were made from myocardial tomograms. In 23 patients with LBBB, 15 patients (65%) developed myocardial perfusion abnormality. In 10 (67%) of these 15 patients, transient perfusion defect appeared in the entire septum (diffuse type). On the other hand in 5 patients (33%), localized fixed perfusion defect developed at the boundary between septum and anterior wall (focal type). In focal type, every patient had other disease such as hypertension, aortic stenosis or sick sinus syndrome. While in patients with diffuse type, other diseases were observed in 30% (p less than 0.05) and they were limited to hypertension or diabetes mellitus. These facts suggested that mechanisms of perfusion abnormalities might be different between these two groups. We compared the perfusion abnormality between LBBB diffuse type and CAD. The extent of the defects was not different between two groups. Although apex was included within the defect in 89% of CAD population, apical defect was observed in only 20% of diffuse type (p less than 0.05). Minimal 201Tl WOR and 201Tl uptake ratio of septum to lateral wall indicated that exercise induced septal defect was slighter in diffuse type than CAD.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602639 TI - [Experimental study on 123I-IMP kinetics in irradiated lung of rabbit]. AB - Radiation-induced alteration of intra-pulmonary kinetics of 123I-IMP was investigated in 11 rabbits received a 50 Gy dose of radiation to the hemithorax. In all of these rabbits examined during 3-17 weeks following the irradiation, an abnormal accumulation was seen in the irradiated lung on the delayed image obtained 60 minutes after the injection of 123I-IMP. The time-activity curves in the irradiated lung following the injection had shallower downslopes of both the initial fast phase and the following slow phase than those of non-irradiated lung, and finally 123I-IMP uptake of the irradiated lung exceeded that of the normal lung. Chest radiographies all of 11 rabbits showed no abnormal shadow and histological studies in 6 of them revealed a relatively slight change or injury of the irradiated lung during 3-17 weeks. These results indicate that this agent may be useful for detecting and assessing relatively early and slight lung injury induced by irradiation. PMID- 1602640 TI - [Clinical study on myocardial imaging with beta-methyl-p-(123I)-iodophenyl pentadecanoic acid in patients with mitochondrial myopathy]. AB - Myocardial imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid (123I BMIPP), a new radiopharmaceutical designed to evaluate myocardial fatty acid metabolism, was performed in 7 patients with mitochondrial myopathy to detect their myocardial damages in comparison with 201Tl myocardial imaging. These patients were divided into 4 chronic progressive external ophthalmoplegia (CPEO) cases, 2 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) cases and 1 myoclonus epilepsy with ragged-red fibers (MERRF). In visual assessment, we observed more myocardial segments with decreased uptake of 123I-BMIPP compared to 201Tl in MELAS cases than in CPEO cases. The mean myocardial uptake of 123I-BMIPP was higher than that of 201Tl in CPEO cases. On the other hand, in MELAS and MERRF cases, the mean myocardial uptake of 123I BMIPP was lower than that of 201Tl. Abnormal findings suggesting myocardial damages were observed in echocardiogram and/or in electrocardiogram in MELAS and MERRF cases, while no such abnormal findings were observed in CPEO cases. Along with the previously reported experimental result that the impairment of rat myocardial mitochondria decreased myocardial uptake of 125I-BMIPP, these results suggest that 123I-BMIPP may be useful to detect myocardial damages in patients with mitochondrial myopathy. PMID- 1602641 TI - [Reassessment of radionuclide-venography for deep vein thrombosis in the lower extremities and pelvic cavity using 99mTc-MAA]. AB - We performed radioisotope (RI)-venography in 31 patients suspected of deep vein thrombosis (DVT), and 18 patients of them (58.1%) had abnormal findings. Out of the 18 patients, 14 satisfied the diagnostic criteria for DVT, that were interruption in the venous flow with the presence of collateral circulation. Sensitivity, specificity and accuracy of RI-venography for DVT were 100%, 76%, 87%, respectively. In all of the patients with chief complaints of edema and pain in the unilateral extremity DVT was found by RI-venography. Lung scan revealed multiple pulmonary perfusion defects in 4 (33.3%) of 12 patients with DVT. Out of the 4 patients, 3 (75%) had silent pulmonary thromboembolism. 99mTc-MAA accumulation was seen in the left lobe of the liver in a patient with occlusion of the IVC and common iliac veins. We are convinced that patients with PTE and/or edema and pain in the unilateral lower extremity should undergo routine RI venography. In conclusion, RI-venography using 99mTc-MAA was reassessed and we obtained the result that it is useful for screening and monitoring DVT and pulmonary thromboembolism. PMID- 1602642 TI - [The value and limitation of resting 201Tl reinjection after stress redistribution imaging for the assessment of myocardial viability: comparison with wall motion improvement by revascularization]. AB - Clinical value and limitation of resting reinjection of small dose of thallium (37 MBq) for the assessment of myocardial viability were evaluated. The results were compared with the degree of wall motion improvement by revascularization to infarcted myocardium supplied by chronic total vessels in 12 patients with old myocardial infarction. Thallium uptake was visually scored and judged as normal, reversible defect (Group 1), new fill in after reinjection (Group 2A), and no fill in even after reinjection (Group 2B). Among 53 segments with initial perfusion abnormality, 21 segments reverted to almost normal, while 32 segments remained abnormal on redistribution images. New fill in after reinjection was observed in 11 segments of 32 segments showing persisting defect on stress and delayed image (37%). Wall motion score index of Group 2A improved significantly higher than Group 2B (p less than 0.01) and almost equal to Group 1, suggesting the utility of reinjection for the assessment of tissue viability which may be underestimated by conventional imaging. But significant wall motion improvement (greater than or equal to 0.6 mean SD/chords) was observed in 6 segments (29%) of 21 segments showing neither redistribution nor fill in after reinjection. These data indicate that small dose of thallium reinjection may enhance detection of viable but jeopardized myocardium, although some underestimation of viability remained to be resolved. PMID- 1602643 TI - [Myocardial perfusion and clearance of 99mTc teboroxime assessed by SPECT]. AB - 99mTc teboroxime is a new myocardial imaging agent that has characteristics of high accumulation in the heart and rapid clearance. We performed tomographic teboroxime study and compared the findings with that of 201Tl. Myocardial teboroxime clearance was calculated by dynamic single photon emission computed tomography (SPECT) using continuous repetitive rotation acquisition method. Teboroxime SPECT image was reconstructed by the three-minute data started from 4 minutes after injection. In 45 myocardial regions (15 patients), complete agreement between 201Tl and 99mTc teboroxime was obtained in 33 regions (73%), when the findings were classified as normal, ischemia and infarction. Significant delay in clearance was seen in the region of coronary stenosis (greater than or equal to 75%) compared with that in the control region (p = 0.0087 at rest, and p = 0.0385 at peak exercise by paired T test). Septum-to-lateral ratios of the clearance and myocardial initial count showed positive correlation (r = 0.743). Further clinical application of this radiopharmaceutical is expected as a new myocardial imaging agent. PMID- 1602644 TI - [Bone scintigraphy in two cases with cough related stress fractures of rib]. AB - Two patients of unusual cough related stress fractures of the ribs are presented. Both patients complained of cough and chest pain with respiratory infection, and the initial chest radiographs showed only an infiltrative shadow due to bronchopneumonia in the lung field, however, failed to reveal any definite osseous abnormality of the ribs. Follow up chest radiographs revealed a callus formation in the fracture sites. In both patients, fracture sites were multiple and located at the axillary line, and radionuclide bone scan disclosed focal abnormal concentrations of activity in these characteristic locations of the lesions. Moreover, there were abnormal accumulation sites in the adjacent above and below ribs, and this finding also seemed to be characteristic of cough related stress fractures of the ribs. PMID- 1602645 TI - [Two cases of hepatobiliary scintigraphy of liver transplantation in rejection]. AB - We reported two patients with liver transplantation who are performed hepatobiliary scintigraphy in rejection. In one patient hepatobiliary scintigraphy shows dilatation of bile duct but it shows good clearance from liver. In another patient hepatobiliary scintigraphy shows delayed clearance from liver. Both patients recovered from rejection. There are four main complications- vascular and biliary abnormality, infection, rejection--after liver transplantation. Hepatobiliary scintigraphy shows almost same findings except biliary complication, so it is difficult to distinguish between infection and rejection. But hepatobiliary scintigraphy may be useful to evaluate transplanted liver function in rejection. PMID- 1602646 TI - [Evaluation of infantile ventricular tachycardia by 201Tl myocardial SPECT]. AB - 201Tl myocardial SPECT findings in infantile ventricular tachycardia (VT) were examined. The subjects were 4 cases of infantile VT subjected exercise-loading 201Tl scintigraphy in 1990. These cases (3 males and 1 female) were aged 11-14 years, being persistent and non-persistent type VT (2 cases each). Echocardiography revealed no abnormal findings in these 4 cases. Exercise-loading was performed by means of sitting ergometer. ECG revealed sinus arrhythmia except for one case which throughout its course of treatment, had already been presenting ventricular extrasystole from before the exercise-loading. Myocardial SPECT revealed persistent defects (anteroseptal wall defects in three case). The above suggests that 201Tl myocardial SPECT enables us to search for etiology of VT, prognosis and the like. PMID- 1602647 TI - [Automatic system design of radioimmunoassay (RIA) laboratory in Yamagata University Hospital]. AB - An originally designed full automatic system for radioimmunoassay (RIA) examination was developed. The system was constructed with mini computer (DOMAIN 3500, Appolo), touch panel controlled personal computer (PC-9801 VM, NEC), printout device (LASER SHOT, Canon) and well-type gamma counter (COBRA, PACKARD). The mini computer was connected with hospital host computer system (FACOM M-760, Fujitsu) to get some patient's information (name, sex, date of birth, department and out-or inpatient). This on-line connection made it possible to simplify the sample registration. Then only the patient's ID-code and examination item were required for sample registration. Sample label, worksheet, report, statistics and register file were able to be printed full automatically. Our new developed system was very useful in search of some patient's previous result. PMID- 1602648 TI - [A guideline for handling radiopharmaceuticals in hospitals]. PMID- 1602649 TI - [Effect of aging on control of breathing]. AB - In an attempt of elucidate the effect of aging on control of breathing, we measured hypercapnic ventilatory responses (HCVR) under three different conditions in 14 elderly volunteers (mean age: 69 yrs) and in young control subjects (29 yrs). There was no significant difference in the slope value (S) of HCVR between the two groups when the test was conducted under hyperoxic conditions. However, under hypoxic conditions, the "S" was significantly increased only in the young subjects, but not so in the elderly. When an resistive load (17 cmH2O/L-sec) was added to an inspiratory line, the "S" was not changed as a result of augmented P0.1 response in the young subjects, while the "S" was significantly decreased without any increase in P0.1 response in the elderly. The dyspnea score at the end-tidal PCO2 of 50 Torr, which was evaluated by visual analogue scale, was consistently higher in the elderly than in the young under any conditions. These results suggest that hypoxic-hypercapnic interaction on ventilation and load compensation reflex to inspiratory resistive loading are impired in the elderly subjects and that these are not associated with bluntness of respiratory sensation. PMID- 1602650 TI - [The mechanism of age-related change in lung elastic recoil pressure]. AB - To investigate the mechanism of age-related change in lung elastic recoil, golden syrian hamsters were divided into three age groups (11-wk group, n = 20; 24-wk group, n = 25; 60-wk group, n = 15). Pressure-volume curves in isolated lungs, length-tension properties of alveolar wall, surface tensions by modified Wilhelmy balance, and collagen and elastin concentrations in the lung tissue were measured. Light and electron micrographs and morphometry were studied. Age related change was not observed in lung elastic recoil in hamsters. However, old hamsters significantly increased a mean linear intercept and the elasticity constant of alveolar wall. On one hand, a surface tension was increased in old hamsters, associating with the decrease in the number of lamellar body of alveolar type 2 cells. These findings suggested that the reduction in lung elastic recoil which should be caused by both the increase in air space and the decrease in extensibility of alveolar wall would be compensated by the increase in surface tension in old hamsters, which may account for the no age-related change in elastic recoil in hamster lungs. PMID- 1602651 TI - [The effect of ageing on airway responsiveness]. AB - In order to evaluate the significance of airway responsiveness in the elderly: 1. Airway responsiveness in the healthy elderly was evaluated and compared with that of the healthy young adults. Methacholine dose response curve was constructed by measuring total respiratory resistance using the modified partial airway occlusion method which provides a simple, convenient, and non-invasive assessment of the resistance of the total respiratory system. Although the responders were fewer and the average threshold values were higher in the elderly, there was no significant differences in the methacholine dose response curve. 2. In vivo and in vitro methacholine dose response relationship was measured in the old guinea pigs (20 to 25 months old) and was compared with that of the young adult guinea pigs. Although no significant differences in the threshold values was observed, the in vivo airway response to the methacholine dose of 1 mg/ml was significantly lower in the old guinea pigs than in the young. The old guinea pig showed small but significant right side shift in the in vitro methacholine dose response relationship. 3. The intra-tracheal instillation of hydrochloric acid to the guinea pig was used as an animal model of aspiration pneumonia. The airway responsiveness was evaluated before and after the instillation. The acid instillation caused the acute and transient bronchoconstriction and the airway responsiveness was markedly increased one hour after the instillation. We conclude that the airway responsiveness may be unchanged or somewhat decreased in the elderly and that the increased airway responsiveness may play a role in the phathologic state such as an aspiration pneumonia. PMID- 1602652 TI - [The characteristic changes of immune function with aging--analysis of the mechanisms]. AB - The most prominent immunological abnormalities in the aged were reduced immune response against foreign antigens and increased auto-antibody production against intrinsic antigen. To explain these immunological abnormalities, we examined the various functions of human lymphocytes from aged and young groups at cellular, molecular and genetic levels. The results indicate: The first, T cells from the aged showed significantly reduced proliferative response not only to specific antigen TAP but also to mitogen PHA or combined stimulation of PMA and ionomycin. The second, the number of IL-2 receptor, particularly high affinity ones, on aged T cells were significantly reduced in the aged after TAP and PHA stimulation. The third, the ability to express Tac (p55) and p70/75 of IL-2R and to internalize the rIL-2 bound to the receptor were reduced in aged T cells. The fourth, although the ability to proliferate in response to SAC stimulation was two folds less in the aged B cells than that in the young ones, the capacity to differentiate into IgG and IgA class ISC after the combined stimulation with SAC and partially purified BCDF were rather increased on the basis of the number of viable cells recovered. The fifth, the amount of IL-2 activity produced by aged T cells was ten fold less than that by young ones, but the amount of BCDF activity produced by aged T cells was three folds higher than that by young ones after PHA stimulation. An inverse correlation between IL-2 activity and BCDF activity was found when the both activities were determined in the same sample.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602653 TI - [Bacterial adherence to the alveolar and respiratory tract system]. AB - Bacterial adherence to the alveolar and respiratory tract system was broadly divided into specific and non-specific adhesion, and effects such as aging were investigated. In specific adhesion, various types of lectin that specifically bind to oligosaccarids as bacterial receptors were used, and lectin specific sugers map of the alveolar and respiratory system were prepared. However, no quantitative difference in oligosaccarids distribution was noted between elderly and young subjects. Meanwhile, in nonspecific adhesion, a study on K. pneumonia infection in mice revealed a pattern of glycocalyx production by the bacteria and their adhesion to the alveolar wall. Clinically, in cases of chronic respiratory infection, a pattern of production of and assembly around glycocalices by P. aeruginosa was observed (biofilm). In vitro tests showed that bacteria in the biofilm are resistant to antibacterial drugs. In the elderly, many factors match the conditions that facilitate the production of glycocalices by bacteria, and many infections of the respiratory organs in the elderly are attributed to nonspecific bacteria adhesion. Infections are thought to become intractable once they extend into biofilm. PMID- 1602654 TI - [Host factors which influence the outcome of pneumonia in the elderly]. AB - We examined 135 elderly patients with pneumonia to clarify the factors predicting on the outcomes of the elderly pneumonic patients. In the fatal cases respiratory symptoms such as cough and sputum, except for dyspnea were less frequent but pulmonary infiltrations on chest roentgenograms were more massive as compared with those in the survived cases. Thus, it was suggested that in the fatal cases the more advanced pneumonia had developed at the time when the diagnosis of pneumonia was made. The fatal cases showed hypoalbuminemia, hypocholesterolemia and hyponatlemia more frequently as compared with survived cases. Among these laboratory values, the decreased serum albumin concentration seemed to be most closely correlated with the fatal outcome of the elderly pneumonic patients. There were significant differences in the outcomes among three groups of the patients, those who were the prolonged bed-ridden, those with severe underlying diseases such as cancer and those treated as out-patients. The out patients showed the most favorable outcome and the prolonged bed-ridden patients the worst outcome. Approximately, 39% of the fatal cases were complicated with multiple organ failure. These results suggest that more important factors which affect the outcomes of pneumonia in the elderly may be not merely aging but the conditions of the host at onset of the disease. PMID- 1602655 TI - [Development and factors related to the appearance of diaphragmatic pleural calcifications--follow up study of employees in an asbestos plant]. AB - Seventy-eight subjects who had continuously worked for more than 25 years until 1985 in an asbestos plant were investigated for diaphragmatic pleural lesions (mainly calcifications) on chest roentgenograms. Diaphragmatic pleural lesions were found in 21 cases (32 sites). Among these cases, calcifications were found in 18 cases (26 sites) and bilateral calcifications in 8 cases. In retrospective observation, 19 sites initially showed diaphragmatic protuberant shadows, and of these, 13 sites subsequently showed calcification in the same positions. The duration between first exposure and appearance of calcification ranged from 15 years to 31 years. The duration of exposure was significantly correlated to the appearance of diaphragmatic pleural calcification, whereas age, smoking habit, and exposure level showed no significant correlation. PMID- 1602656 TI - [Nonadrenergic noncholinergic inhibitory nervous system in guinea pig airway]. AB - It has been reported that tracheal smooth muscle of guinea pig is innervated by both the adrenergic and nonadrenergic noncholinergic (NANC) inhibitory nervous system. However, NANC inhibitory nerve supply to the lower airway of guinea pig has not yet been demonstrated in in vivo experiments. We performed the present study to evaluate the physiological role of NANC inhibitory nerves in tracheal smooth muscle of guinea pig in vitro, and in anesthetized guinea pigs in vivo. Innervation of NANC inhibitory nerves to tracheal smooth muscle was much greater than that of adrenergic nerves (77.8 +/- 3.8%, 22.2 +/- 3.8%, respectively, p less than 0.01). Neither decrease in RL nor increase in CL, however, was observed with vagal stimulation during serotonin infusion after the administration of propranolol. The role of NANC inhibitory nerves in histamine-induced bronchoconstriction (HIB) was investigated. HIB was enhanced by vagotomy in guinea pig pretreated with propranolol (p less than 0.01). These results suggest the role of the NANC inhibitory nervous system in the attenuation of HIB in vivo in the guinea pig. PMID- 1602657 TI - [Evaluation of interstitial shadows by thin slice computed tomography]. AB - We developed a method for evaluation of interstitial shadows by thin slice computed tomography (CT). We studied thirty-seven cases with interstitial shadows confirmed by thin slice CT, and 13 normal cases. Thin slice CT was scanned on 3 levels: 1) at the aortic arch, 2) about 2 cm below the carina, and 3) about 1 cm above the right diaphragm. Each level was scanned bilaterally to produce 6 regions of interest (ROI); CT numbers were recorded from each ROI. CT numbers ranging from -1000 to 100 Hounsfield units (H.U.) were classified into 4 different bands, -1000 - (-900) H.U. (low band), -900 - (-750) H.U. (medium low band), -750 - (-500) H.U. (medium high band), and -500 - 100 H.U. (high band), for cases with interstitial shadows and for normal cases. We calculated the prevalence of CT numbers in each band for both normals and subjects with interstitial shadows. Compared to the normals, subjects with interstitial shadows showed fewer pixels in the medium low band and more pixels in the medium high and high bands. Furthermore, the prevalence of CT numbers in each band correlated with %TLC, %VC, and pulmonary diffusing capacity. We conclude that thin slice CT is a useful method for evaluation of the extent and characteristics of interstitial shadows. PMID- 1602658 TI - [Therapy and clinical symptoms in patients with obstructive sleep apnea in Japan]. AB - To investigate the long-term outcome of therapy and clinical symptoms of patients with OSAS (obstructive sleep apnea syndrome) in Japan, we studied 34 patients with OSAS who had been diagnosed by standard polysomnography more than one years (36.0 +/- 19.7 months: mean +/- SD) previously. They were 53.8 +/- 10.5 years old, body mass index was 27.8 +/- 5.2 kg/m2, and AHI (apnea & hypopnea index) was 50.0 +/- 24.2/h. The subjects had achieved weight loss (p less than 0.01), but had regained their initial weight at our follow-up. Eleven patients with OSAS were initially candidates for NCPAP (nasal continuous positive airway pressure), but only 5 patients used it for a prolonged time. The other 6 patients with OSAS could not use NCPAP because they did not wish to purchase a NCPAP instrument. One of 5 patients who used NCPAP for a long time died from lung cancer; thus, 4 patients used NCPAP continuously. Ten patients were commenced on ACZ (acetazolamide); however, only 5 patients took it continuously. ACZ resulted in some improvements in the sleep parameters (AHI index, desaturation time below SaO2 90%), but apnea & hypopnea duration and the difference in transcutaneous PCO2 between wake and sleep were not significantly improved by ACZ administration. ACZ was not as effective as NCPAP. Almost 60% of patients with OSAS had excessive daytime sleepiness. Hypertension was detected in about 60% of patients. Nine of 25 patients who had an automobile license had had more than one automobile accident. Nine patients who had had more than one automobile accident showed AHI greater than or equal to 30 in our study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602659 TI - [Experimental study of the pathogenesis of radiation pneumonitis]. AB - Radiation pneumonitis is a well-recognized complication of therapeutic thoracic irradiation that is occasionally fatal. However, its pathogenesis remains unclear. In this report, to define the mechanism of radiation pneumonitis, bronchoalveolar lavage findings and nitroblue tetrazolium reduction of alveolar macrophages were studied and compared with histopathological findings following 40 Gy X-ray irradiation to the right hemithorax of rats. The total number of cells was significantly increased and the percentage of alveolar macrophages was significantly decreased at 28 days after irradiation. At that time, the percentages of lymphocytes and neutrophils were increased and acute inflammatory changes had appeared histopathologically. Nitroblue tetrazolium reduction of alveolar macrophages was significantly increased at 21 days after irradiation. This shows that activation of alveolar macrophages occurs before the completion of radiation pneumonitis, and it is suggested that these activated alveolar macrophages play a major role in the pathogenesis of radiation pneumonitis. PMID- 1602661 TI - [Bronchial hyperresponsiveness to histamine induced by intravenous administration of leukotriene C4 (LTC4) and LTD4 in guinea pigs]. AB - Leukotriene (LT) has been suggested to play an important role in the pathogenesis of bronchial asthma. In the present study, the effects of intravenous administration of LTC4 and LTD4 on bronchial smooth muscle in guinea pigs were investigated by measurement of dynamic compliance and dynamic respiratory resistance using a formula that excludes the effect of differences in airway wall thickness. With this formula, the ratio of bronchial smooth muscle constriction by histamine can be estimated as an index of bronchial hyperresponsiveness. Administration of LTC4 and LTD4 induced airway wall edema. The ratio of bronchial smooth muscle constriction by histamine was significantly enhanced by the administration of LTC4 and LTD4. Moreover, the LT antagonist ONO-1078 inhibited the effect of LTC4 and LTD4 administration. These results suggest that LTC4 and LTD4 can be important mediators affecting bronchial hyperresponsiveness. PMID- 1602660 TI - [Clinico-pathological study of collagen-related pulmonary lesions in cases of open lung biopsy]. AB - We studied the clinico-pathological correlation of collagen disease-related pulmonary lesions to examine the pathological and radiological features of collagen lung, and the effect of steroid therapy. Ten open lung biopsy cases were examined; 4 male, and 6 female. The mean age was 55 years old. Seven cases developed pulmonary shadows after the diagnosis of collagen disease, and 3 cases showed pulmonary shadow prior to diagnosis. Pathologically, 6 cases proved to be bronchiolitis obliterans organizing pneumonia (BOOP), 3 cases were chronic interstitial pneumonia (UIP), and 1 case was acute interstitial pneumonia. All cases had inflammatory thickening of the interstitium involving the pleura, bronchial wall, and perivascular connective tissue. Half of the cases had bronchiolar inflammatory lesions. Radiologically BOOP cases showed either localized ground glass shadows, or diffuse reticulonodular shadows predominantly in the lower lung fields with shrinkage of affected areas. UIP cases showed reticulonodular shadows, and active UIP cases showed overlapping ground glass shadows. Steroids were administered in cases of BOOP and active UIP, and all cases showed improvement. We consider that open lung biopsy is of use in the diagnosis of some cases and in assessing whether steroid therapy is indicated. PMID- 1602662 TI - [A case of lung cancer in a patient with von Recklinghausen's disease]. AB - A 57-year-old man was admitted to our hospital for further investigation of an abnormal shadow in his chest X-ray. He had cafe-au-lait spots and multiple subcutaneous neurofibromas and was diagnosed as having von Recklinghausen's disease. Bronchofiberscopy was performed, but an adequate specimen was not obtained. Therefore, percutaneous needle biopsy was performed, and the specimen showed poorly-differentiated adenocarcinoma. The left subclavian artery was deviated on aortography, therefore, neoadjuvant chemotherapy with CDDP & VDS was performed. He subsequently underwent left upper lobectomy. Pathologically, the tumor cell showed necrosis and scarring. Including this case, there have been 11 reports of von Recklinghausen's disease associated with lung cancer in the Japanese literature. Adenocarcinoma was observed in 72.9% of cases, and poorly differentiated tumor was observed in 7 out of 8 patients with distinct tumor differentiation. PMID- 1602663 TI - [Minocycline-induced pneumonia and pleurisy--a case report]. AB - A 24-year-old woman had been treated with minocycline (MINO) for acute upper airway infection. Two days after the start of MINO therapy, she developed fever, cough, dyspnea, and bloody sputum. Her chest X-ray film revealed bilateral pleural effusions and butterfly shadow, and chest computed tomography revealed markedly increased density of pulmonary tissue in the central lung fields. Arterial blood gas analysis demonstrated severe hypoxemia. The characteristics of the pleural effusion were exudative. Based on the history of her illness and the chest X-ray findings, in addition to the laboratory findings of leukocytosis with eosinophilia and increased serum IgE, drug-induced pneumonia was suspected. Once the treatment with MINO was discontinued, her symptoms, laboratory data, and chest X-ray findings improved rapidly. Microscopic examination of a transbronchial lung biopsy specimen showed increased alveolar septal thickness with formation of Masson's bodies. Although the result of a lymphocyte stimulation test was negative for MINO, the skin test was positive for immediate response. Because of her clinical course, the possibility of induction by other drugs was excluded. This patient was therefore diagnosed to have MINO-induced pneumonia. To date, ten cases of MINO-induced pneumonia have been reported, but no previous case was associated with pleurisy. PMID- 1602664 TI - [A resuscitated case of sleep apnea syndrome with cardiac arrest]. AB - A 71-year-old man was noted to habitually snore loudly at night and have a predisposition to somnolence during the daytime. While dozing during the day, he developed cardiac arrest at the time when snoring stopped, and was resuscitated. By means of a respiration monitor, he was diagnosed as having sleep apnea syndrome (SAS) with a combination of obstructive, central, and mixed type. However, neither respiratory insufficiency nor cardiac insufficiency was observed, and there were no abnormal findings on laboratory tests and bronchoscopy. SAS complicated by cardiac arrest is usually seen in cases with concomitant symptoms such as excessive obesity, hypertension, arrhythmia, right heart insufficiency, secondary polycythemia, or mental disorder. The present case abruptly developed cardiac arrest in the absence of such symptoms. This case therefore suggests the importance of screening tests using a respiration monitor during sleep in subjects who have a loud snore or a predisposition to somnolence during the daytime. Although treatment with UPPP alone had no noticeable effect, UPPP treatment combined with sleeping in the lateral position was effective in the present case. The efficacy rate of UPPP has been reported to be 50 to 60%. The early establishment of a method for precise evaluation of the site of obstruction as well as criteria for appropriate application of UPPP are urgently required. PMID- 1602665 TI - [A case of malignant pleural mesothelioma with osseous and cartilaginous formation]. AB - A 85-year-old man was admitted to our unit on November 17, 1989 with bloody sputum and abnormal shadow on chest X-ray film. Chest X-ray and CT on admission showed a large tumor mass approximately 9 cm in diameter in the right middle and lower lung field. Microscopic examination of the needle biopsy specimen from the tumor revealed biphasic malignant pleural mesothelioma. After admission, thoracentesis was performed, because of rapidly increasing right-sided pleural effusion. One of the two trochar catheter was inadvertently inserted in the tumor. Tumor tissue obtained through the catheter showed malignant mesothelioma with osseous and cartilaginous formation. Only isolated reports by Goldstein and Yousem have reported osseous and catilaginous differentiation in malignant mesothelioma. To our knowledge, this is the first reported case in Japan. PMID- 1602666 TI - [Pulmonary infection caused by Mycobacterium gordonae (M. gordonae) in a healthy middle-aged male]. AB - A 51-year-old man was admitted to our hospital in July 1989 because of an abnormality in his chest radiograph. On his yearly health check-up, an abnormality of his chest radiography was first noted in June 1988. At that time, examinations including bronchoscopy were performed but no specific diagnosis was made. On admission, his chest radiograph revealed new infiltrates at the apex of the right lung which were not present in June 1988. Three out of 5 consecutive sputum specimens after admission produced a pure growth of 100 colonies to 1+ of acid-fast bacilli (AFB). This AFB was scotochromogenic, and hydrolysis of Tween 80 at 5 days was positive. It did not reduce nitrate, and niacin test was negative. It was sensitive to ethambutol at a concentration of 5 micrograms/ml, and was not tolerant to 0.2% picric acid. We thus identified this AFB to be M. gordonae. The patient was treated with rifampicin (450 mg/day), isoniazid (400 mg/day), and ethambutol (1000 mg/day) for 9 months. After 2 months of treatment the sputum cultures became negative, and the chest radiograph showed improvement of the infiltrates. M. gordonae is considered to be one of the least pathogenic AFB to man. Most recent reports of M. gordonae infection have been in immunocompromized hosts or patients with a history of pulmonary tuberculosis. The present case is a very rare example of this organism affecting a healthy male, and thus yields new information on the pathogenesis of M. gordonae in man. PMID- 1602667 TI - [A successful treatment of patient with paraquat poisoning]. AB - A 60-year-old man was admitted 1 hour after ingesting approximately 40 ml of Gramoxon (paraquat) in an attempt to commit suicide. Gastrointestinal lavage, compulsory urination, and direct hemoperfusion (DHP) were immediately performed to remove the paraquat. He was then administered Vitamin E and high dose methylprednisolone therapy to prevent lung injury. Chest roentgenogram on the 3rd day showed ground glass appearance in the outer zone of bilateral lung fields. Chest CT scans on the 9th day revealed a faint high density area in the same area, suggesting interstitial change. The shadows gradually improved and had disappeared on the 35th day after admission. Serum superoxide dismutase (SOD) activity, measured by electron spin resonance spectroscopy, was undetectably low until the 22nd day, and then increased into the normal range. It was suggested that SOD was consumed to neutralize the paraquat toxicity. Serum SOD activity changed according to the paraquat activity, and was a useful indicator of paraquat toxic activity. He was discharged without any symptoms 50 days after admission. PMID- 1602668 TI - [A case of allergic bronchopulmonary candidiasis treated with amphotericin B inhalation]. AB - A 77-year-old man underwent emergency admission for nocturnal asthmatic attack. Although his asthmatic attack improved within a few days with treatment including systemic corticosteroid, bilateral recurrent infiltrative shadows developed in his chest roentgenogram in association with a further exacerbation of dyspnea. Various antibiotic agents were given; however, the pulmonary infiltration did not improve. He was transferred to our department with the diagnosis of intractable pneumonia. C. albicans was detected in the sputum, and both IgE antibody and precipitating antibody specific for C. albicans were positive. Immediate cutaneous reactivity to C. albicans was positive even with a million-fold dilution of antigen extract C. albicans was also detected in bronchoalveolar lavage fluid. A diagnosis of allergic bronchopulmonary candidiasis was made. Chest roentgenographic findings as well as clinical symptoms improved with inhalation of 50 mg of amphotericin B. PMID- 1602670 TI - [The 32nd general meeting of the Japan Society of Chest Diseases. Hokkaido, May 12-14, 1992. Abstracts]. PMID- 1602669 TI - [Application of nasal intermittent positive pressure ventilation to a case of limb-girdle muscular dystrophy]. AB - We applied nocturnal ventilation (NV) with nasal intermittent positive pressure ventilation with custom molded mask (NIPPV-C Mclermott, 1989), as well as NV with tracheostomy intermittent positive pressure ventilation (TIPPV) to a male patient with limb-girdle muscular dystrophy who had developed chronic respiratory failure at the age of 47. NV with both methods successfully corrected nocturnal hypoxemia, improved daytime arterial blood gas values, and achieved a stable clinical course without marked deterioration for four years. Daytime PaO2 higher than 60 Torr and PaCO2 lower than 70 Torr while breathing room air were maintained with both methods, whereas PaO2 was lower than 50 Torr and PaCO2 higher than 70 Torr before the implementation of NV. TIPPV was safely suspended repeatedly for as long as two weeks, maintaining daytime PaO2 higher than 50 Torr. NIPPV-C was also repeatedly suspended for two weeks. Occasionally PaO2 dropped as low as 40 Torr after periods without NV; however, it was restored to higher than 60 Torr after one or two nights' NIPPV-C. These facts suggest that NV had a restorative effect on respiratory muscle fatigue in the present case. While on NIPPV-C, nighttime SaO2 was higher than 90% for 94% of the total time, and between 80% and 90% for the remaining 6% of the time. Desaturation for short periods was thought to be due to oral air leakage, which made the method slightly less effective than TIPPV. However, the overall clinical effectiveness of NIPPV-C was comparable to that of TIPPV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602671 TI - [Surgical repair of coarctation of the aorta during infancy]. AB - Fourty-six infants less than 1 year of age underwent repair of coarctation of the aorta in our institution between 1972 and 1991. Pathologic types and numbers of patients were simple coarctation (Group 1) in 7 patients, with ventricular septal defects (Group 2) in 22 patients and with complex cardiac anomalies (Group 3) with 17 patients. A patent ductus arteriosus was present in 43 of these patients. Operative technique used were resection and end-to-end anastomosis (RETE) in 30 patients, subclavian flap angioplasty (SFA) in 15 and Blalock-Park operation in one patient. RETE procedures were employed from 1972 until 1980 and SFA procedures were employed between 1981 and 1985. After 1986 RETE procedures were employed again. The operative mortality rates were 0% (0/7) in Group 1, 9.1% (2/22) in Group 2 and 82.3% (14/17) in Group 3. The high mortality rate in Group 3 are thought to be related to severe associated cardiac anomalies. There were no significant differences in the operative mortality and recurrent coarctation rates between RETE and SFA procedures in Group 1 and 2. In patient with a large associated intracardiac shunt (Group 2 and 3) banding of the main pulmonary artery (PAB) was performed with coarctectomy simultaneously. In Group 2 VSD closure and debanding could be done a few months later with excellent results, but in Group 3 primary repair of cardiac anomalies may be worth to try since results of coarctectomy with palliative procedures in these group of patients were poor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602672 TI - [Complications of Nd-YAG laser treatment on tracheobronchial lesions]. AB - Neodymium-yttrium-aluminum-garnet (Nd-YAG) laser was clinically introduced to the treatment of tracheobronchial lesions 10 years ago. Since then, the apparatus of the laser therapy and the flexible bronchoscopy have been improved, and the indication for its treatment has been established. Nd-YAG laser is useful at the field of the treatment of the tracheobronchial stenotic or obstructed lesions. But various complications occur, because of the lesions occupying in the narrow tracheo and bronchial lumen. In our institute, 83 cases have been treated in 196 sessions (from one to fifteen sessions per patient) for the past ten years. The stenotic or obstructed lesions were divided into three etiologies, 64 cases with malignant lesion, 8 cases with post operative granulation at the suture line and 11 cases with benign lesion. All procedures were performed under local anesthesia by using flexible bronchoscope. Among them, complications were noticed in eleven cases. They involved hemorrhage (6 cases) and respiratory disturbances (2 cases) during operative period, and massive hemorrhage (2 cases) and edema of the tumor (1 case) in the adjacent period of laser treatments. PMID- 1602674 TI - [A holder for right-angled metal cannula (Pacifico's venous cannula) for direct superior vena caval cannulation]. AB - In pediatric open heart surgery, a right-angled metal cannula (Pacifico's venous cannula) for direct superior vena caval cannulation is frequently used. But it is often difficult to be inserted into superior vena cava due to "right-angled" shape especially in small babies. We developed a new holder which can make straight line from the metal tip to flexible plastic end of the cannula. It is easy and safe even in cases of small babies. PMID- 1602673 TI - [Assessment of Blalock-Taussig shunts in children with complex cardiac anomalies associated with reduced pulmonary blood flow and total anomalous pulmonary venous drainage]. AB - Eleven patients with syndromes of asplenia and polysplenia associated with total anomalous pulmonary venous drainage (TAPVD) were underwent Blalock-Taussig (B-T) shunt operation for reduction of pulmonary blood flow. The age of patients at operation were 6 days to 5 years (average 19.5 +/- 18.7 month). There were seven patients in supracardiac type and four in cardiac type of TAPVD. All patients didn't present obstruction to pulmonary venous return (PVO) before B-T shunt operation. There were one early (9%) and two late deaths (20%) after surgery. Although the hospital death was related to perioperative errors. Two late deaths were not due to the PVO. One of infants had moderately pulmonary congestion and cardiac failure after shunt procedure. Two patients were measured pressure gradient (3 to 4 mmHg) between common pulmonary vein to atrium chamber before shunt procedure. Repeated catheterization revealed that 6 of them could be measured pressure gradient, 3 to 7 mmHg, and no patients had clinical sign of the PVO. Our results demonstrated that B-T shunt operation could be satisfactory for syndromes of asplenia and polysplenia associated with reduced pulmonary blood flow and TAPVD. PMID- 1602676 TI - [Biventricular heart assist using centrifugal pump and roller pump in profound ventricular failure after open heart surgery: a case report]. AB - A forty-seven-year-old female with profound biventricular heart failure probably caused by coronary artery spasm after open mitral commissurotomy was successfully survived by mechanical circulatory support. Centrifugal and roller pumps were applied to left and right side circulatory assist respectively. Recovery of cardiac function was evaluated by transesophageal echocardiography and hemodynamic parameters during intentional low flow assist. Finally, she was weaned from assist after 136 hours. No systemic thromboembolism was recognized after pump removal. Combination of centrifugal and roller pumps could be applicable to biventricular heart assist without crucial complication. PMID- 1602675 TI - [Clinical report of cimetidine therapy for the prevention of the gastro-duodenal bleeding after the open heart surgery]. AB - The efficacy of cimetidine administration after the open heart surgery was studied using the cimetidine concentration examination in the twenty five consecutive cases. Cimetidine was administered intravenously. The cases were divided into five groups for the infusion period. There was no case which developed the gastro-duodenal bleeding after the surgery. The concentration of cimetidine has showed more than 0.5 microgram/ml in each group. It was concluded that the administration of 800 mg cimetidine infused more than three hours, repeated every twelve hours was the possible treatment for the prevention of the gastro-duodenal bleeding after the open heart surgery. PMID- 1602677 TI - [A case of subglottic tracheal stenosis following tracheostomy successfully treated with laryngo-tracheal anastomosis]. AB - A 77-year-old male patient underwent laryngo-tracheal anastomosis for subglottic tracheal stenosis. He developed exertional dyspnea 10 month after tracheostomy. Anterior and lateral wall of the cricoid cartilage and the first two tracheal cartilages were resected, preserving the recurrent laryngeal nerves. The distal trachea was anastomosed to the thyroid cartilage primarily and tracheostomy was made at 6th tracheal ring. Postoperatively, anterior flexion of the neck was maintained for a week. Oral intake was started on the 2nd postoperative day. The patient showed smooth recovery. The important points of this operation are: 1) preoperative evaluation of the residual subglottic space, 2) intraoperative care for preservation of the recurrent nerves, especially at the lateral sides of the crycoid cartilage, and 3) postoperative maintenance of the cervical anterior flexion. PMID- 1602678 TI - [Pseudoaneurysm of the left ventricle following mitral valve replacement]. AB - This report describes a false aneurysm of atrioventricular groove in the patients who underwent the reoperation of the mitral valve replacement (MVR). Patient 1 underwent reMVR with a SJM prosthesis because of the malfunction of the previous prosthetic valve. A large hematoma was observed in the posterior atrioventricular groove with bleeding at weaning from cardiopulmonary bypass. Ventricular rupture was repaired under the cardioplegic arrest successfully from the epicardial surface with a woven Dacron felt. The postoperative left ventriculogram revealed the false ventricular aneurysm along the atrioventricular groove. Patient 2 underwent reMVR with Carpentier-Edwards prosthesis because of the malfunction of the previous Carpentier-Edwards prosthesis. Cardiopulmonary bypass was discontinued uneventfully, and there were no clinical symptoms suspicious of the formation of the false left ventricular aneurysm. The left ventriculogram at the discharge showed the false left ventricular aneurysm along the atrioventricular groove. Although both patients are in good condition without significant complications, we should involve in the postoperative care of the patients on a regular outpatient basis. PMID- 1602679 TI - [Carpentier's procedure for Ebstein's anomaly: successful and failed cases]. AB - Two adult cases of Ebstein's anomaly underwent Carpentier's procedure. In the first case longitudinal plication limited to free wall of atrialized ventricle was performed and postoperative course was uneventful. In the second case preoperative echocardiography showed apparently restricted movement of anterior leaflet of the tricuspid valve which was compatible with intraoperative findings. That is, inferior edge of anterior leaflet was partly adherent to ventricular wall and systolic bulging of leaflet was significantly impaired which was left untouched but should be repaired by additional procedure. Six days after operation the tricuspid valve replacement was required for persistent right heart failure due to residual tricuspid regurgitation. In the same case longitudinal plication of atrialized ventricle reported by Carpentier and colleagues resulted in excessively small annulus. Therefore we had to reduce the plication and did not perform following atrial plication to avoid direct injury to conduction system or disturbing coronary venous return. In conclusion exact preoperative evaluation of anterior leaflet of the tricuspid valve especially subvalvular anatomy is essential to Carpentier's procedure, as Carpentier and colleagues emphasized, and conservative longitudinal plication of the atrialized ventricle limited to free wall is favorable when excessively small annulus might be concerned. PMID- 1602681 TI - [Bicuspid aortic valve with sudden onset of aortic insufficiency due to rare causes: report of two cases]. AB - This report describes two cases of aortic valve replacement which was warranted by the suddenly developed aortic regurgitation due to a congenitally bicuspid aortic valve. Aortic insufficiency was caused by the rupture of the strand which lifted a larger cusp to the aortic wall in one, and by the perforation of valvular aneurysm in another. Reviewing the literature these types of aortic insufficiency are rarely reported. PMID- 1602680 TI - [Four cases of spontaneous pneumothorax with no reexpansion of collapsed lung despite chest tube drainage]. AB - We report four cases of spontaneous pneumothorax with no reexpansion of the collapsed lung despite chest tube placement and adequate suction. The cause of absence of reexpansion was endobronchial obstruction by bronchogenic carcinoma in one patient and by sputum plug in another. In the other two patients, the collapsed lung had pulmonary fibrosis and did not reexpand at all because of reduced pulmonary compliance. PMID- 1602682 TI - [A resected case of thymolipoma]. AB - We reported a resected case of thymolipoma, which has been hardly experienced. The patient was 21-year-old female and consulted a doctor for general fatigue. Chest roentgenogram revealed a mass-like shadow at the right lower mediastinum, which was suspected mediastinal tumor. The mass of right anteroinferior mediastinum, which was clearly shown by chest CT scan and MRI, was continued to the right lobe of the thymus. Under a diagnosis of anterior mediastinal tumor, operation was carried out. The tumor, which was 10 x 8 x 7 cm in diameter and 160 g in weight, was removed together with right lobe of the thymus. Histological diagnosis of thymolipoma was obtained from the resected specimen. PMID- 1602683 TI - [A case of straddling tricuspid valve associated with VSD]. AB - A case of straddling tricuspid valve associated with VSD was presented, who was diagnosed as VSD with pulmonary hypertension but not diagnosed as straddling in preoperative state. Two-dimensional echocardiography did not demonstrate a small right ventricle and overriding of tricuspid valve to the ventricular septum. Operative findings were as follows; the VSD was common A-V canal type and anomalous chordae of septal leaflet of tricuspid valve crossed through the VSD and attached to the contralateral side of the ventricular septum. We tried to preserve the anomalous chordae to prevent tricuspid regurgitation, so that we carried out patch closure of VSD. To avoid injury conduction system stitches were placed from upper margin of the VSD, and to keep away tricuspid regurgitation we plicated a depression of septal leaflet which caused by anomalous chordae in VSD patch closure. In postoperative state, A-V block did not arise and tricuspid regurgitation was shown a little as well as preoperative state. PMID- 1602686 TI - [Intravascular hemolysis due to residual shunt after patch closure of VSD: a case report]. AB - A patient with intravascular hemolysis due to residual shunt after patch closure of VSD was presented. The patient was 31-day-old female. She underwent VSD closure with Dacron patch 2 weeks after the initial operation (subclavian flap method) for coarctation concomitant with VSD. Soon after the operation, severe intravascular hemolysis and hemolytic anemia appeared. Conservative therapies were not effective, and her general condition got worse gradually. Forty days after closure of VSD, she underwent reoperation and the shunt was closed. Hemolysis disappeared dramatically. It was suggested that early reoperation was necessarily when severe intravascular hemolysis due to residual shunt after patch closure of VSD had persisted. PMID- 1602685 TI - [An adult case of anomalous origin of the left coronary artery from the pulmonary artery]. AB - An adult case of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) was presented. A 37-year-old male was admitted for ventricular arrhythmia and chest pain. The catheterization, left ventriculography and coronary arteriography revealed ALCAPA with anterolateral ventricular aneurysm and mild mitral regurgitation. An operation using Takeuchi procedure was performed. The postoperative course was uneventful and the results of the catheterization, left ventriculography and coronary arteriography performed immediately and five years after the operation were excellent except mild supravalvular pulmonary stenosis. Six years later, the patient is asymptomatic and well. PMID- 1602684 TI - [A case report of a massive pulmonary tumor embolism occurring during surgery for renal cell carcinoma]. AB - A 59-year-old man, who suffered a massive pulmonary tumor embolism during surgery for renal cell carcinoma with vena caval invasion, was treated by emergency pulmonary embolectomy using cardiopulmonary bypass. Renal cell carcinoma occasionally extends into the inferior vena cava (IVC) as a tumor thrombus. In such patients, removal of the tumor thrombus from the IVC has to be performed in addition to radical nephrectomy. However, the massive pulmonary tumor embolism is a major potential hazard during radical surgical resection. To prevent intraoperative pulmonary embolisms from occurring, scheduled use of cardiopulmonary bypass with the cooperation of cardiovascular surgeons is recommended. PMID- 1602687 TI - [A case of post infarction true left ventricular aneurysm which showed pseudoaneurysm-like shape in left ventriculography]. AB - A 69-year-old man who had a post-infarction left ventricular aneurysm underwent surgical repair. Preoperative left ventriculography showed a small aneurysm, 3.0 x 3.0 x 2.5 cm in size, with a narrow neck at the inferior wall suggesting a typical "false" aneurysm. But intraoperative and pathological examination revealed that this was a "true" aneurysm which contains coronary artery and myocardial cells in its wall. Left ventriculography is not necessarily the definite standard to differentiate between true and false left ventricular aneurysm. PMID- 1602689 TI - [An operated case of traumatic intrapulmonary foreign body persisting for 45 years]. AB - A case with a bronchial foreign body which had an uncommon way of entry through a wound in the chest wall was described. A 70-year-old man was admitted to our hospital because of productive cough and weight loss. He had been injured by a fragment of a hand grenade which penetrated his anterior chest wall at the front in China 45 years ago. A chest x-ray film revealed a metallic foreign body, measuring 1.3 by 0.9 cm, in the upper lobe of the right lung. Computed tomography of the chest and bronchoscopy demonstrated a steel fragment lodging beside and in the right upper lobe bronchus. Right upper lobectomy was performed, and the patient remains well without any thoracic symptoms one and a half years after the operation. Problems in the treatment of traumatic intrapulmonary foreign bodies were discussed. PMID- 1602688 TI - [A case of postpneumonectomy empyema cured by open drainage thoracotomy and thoracoplasty with pectoral myoplasty]. AB - The patient was a 57-year-old male with lung adenocarcinoma arising in right upper lobe. Because the tumor invaded to the trunchus intermedius and B6, right upper lobe, middle lobe and S6 was resected with bronchial plasty which was performed between the main bronchus and basal bronchus. Because the bronchial fistula appeared after 12 days of operation, completion pneumonectomy was performed, and the stump of the main bronchus was covered with intercostal muscle. Although fistula of the bronchial stump did not appear, open drainage thoracotomy was performed because of deterioration of empyema due to methicillin resistant staphylococcus aureus (MRSA). After 10 weeks of open drainage, although MRSA did not disappear, the thoracoplasty with interthoracic transposition of the major and minor pectoral muscles was performed. Empyema was cured, and the patient left the hospital 2 weeks after thoracoplasty. Thoracoplasty with pectoral myoplasty was useful for single-staged closure of post-pneumonectomy empyema. PMID- 1602690 TI - [Superior posterior mediastinal neurinoma with extrathoracic extension]. AB - We have encountered a case of superior mediastinal neurinoma which grows through the intercostal space and advances into the erector spinal muscles. Neurinoma which shows such a growth pattern is rare. MRI is useful in making preoperative evaluation. For operation, non-open chest extrapleural extirpation was successfully performed by the supraclavicular and posterior approach. This type of operation has the following advantages: surgical stress is less; postsurgical pain is mild, etc. PMID- 1602691 TI - [Successful operation for atrial septal defect in a patient with Gilbert's syndrome]. AB - We report a rare case of atrial septal defect (ASD) with Gilbert's syndrome. The patient was a 34-year-old man, who underwent successfully patch closure for ASD, and annuloplasty for tricuspid valve regurgitation by DeVega's method. Gilbert's syndrome is a disorder characterised by a unconjugated hyperbilirubinemia without other hepatic dysfunction. In our case, there was no evidence of hepatic damage related to hyperbilirubinemia postoperatively. Open heart surgery for patient with Gilbert's syndrome is supposed to be performed rather safely. PMID- 1602692 TI - [A successful surgical case of thoracoabdominal aortic aneurysm ruptured into the right pleural cavity]. AB - A 55-year-old man was transferred to our cardiovascular center because of right hemothorax and hemorrhagic shock. Emergency CT scan revealed a thoracoabdominal aortic aneurysm (Crawford's type I-A) ruptured into the right thorax. The aneurysm was exposed by Stoney's spiral opening approach. A 24 mm Cooley Dacron graft was implanted in end-to-end fashion between the descending thoracic aorta and the abdominal aorta just above the celiac artery. The use of aortic artery cannula, femoral artery cannula and flexible polyvinyl tube provided safe and simple means as a temporary bypass during this graft replacement. Postoperative course was uneventful. PMID- 1602693 TI - Computer systems: answers to your prayers. PMID- 1602694 TI - Creating the future: collaborative practice between emergency and critical care nurses. PMID- 1602695 TI - Is the sale of Board of Registration in Nursing mailing lists potentially dangerous? PMID- 1602697 TI - Stand together and be recognized: use only one academic degree and one professional designation after a nurse's name. PMID- 1602696 TI - Standards not the answer to difficult flight nursing decisions. PMID- 1602698 TI - Steroid dosage in spinal cord injury clarified. PMID- 1602699 TI - American versus Canadian patients' dissatisfaction with ED waits. PMID- 1602700 TI - Efficacy and safety of povidone-iodine underscored. PMID- 1602701 TI - Waiting room bulletin board educates ED patients and families. PMID- 1602702 TI - ED nurse transport of cardiac patients questioned. PMID- 1602703 TI - Tachycardia can be indicator of shock in children. PMID- 1602704 TI - A 22-month-old victim of near drowning. PMID- 1602705 TI - Medical and forensic examination by a sexual assault nurse examiner of a 7-year old victim of sexual assault. PMID- 1602706 TI - Trauma scoring and pediatric patients: issues and controversies. AB - In summary, controversy exists as to the use of trauma scoring in pediatrics. No one currently available trauma score is ideal for use with all patients. To address these issues, the impact of major trauma on children must be more clearly defined in relation to the impact of trauma on adults. Areas for ongoing research include analysis of the clinical implications of pediatric differences in response to trauma, comparison of prehospital and ED trauma scoring, and further studies using large samples of reliability and validity of various trauma scores. A trauma score is an adjunct to--not a substitute for--a full and ongoing clinical assessment. When using adult scoring systems with children, it is important to remember that normal values for an adult are not necessarily normal for a child. Recognizing the differences between adults and children is an essential first step in assessing and managing the effects of injury in children. PMID- 1602707 TI - Sources of stress for emergency nurses in four urban Canadian emergency departments. AB - The results of this study indicate that emergency nurses experience work-related stress originating from a variety of sources. Although the study included a group of emergency nurses committed to achieving a high standard of patient care, many of the key stressors they confront hinder their sense of achievement. Repeatedly, nurses described inadequate staffing and resources, too many nonnursing tasks, changing trends in ED use, and patient transfer problems as having considerable impact on their ability to provide quality patient care. Nurses were also stressed by continual confrontation with patients and families who exhibited crisis or problematic behavior. In addition to strategies dealing directly with these stressors, the creation of a workplace that fosters more support and recognition of nurses and promotes professional growth may also help to reduce the impact of work stress for emergency nurses. PMID- 1602708 TI - The sexual assault nurse clinician: a fifteen-year experience in Minneapolis. PMID- 1602709 TI - The sexual assault examination: overview and lessons learned in one program. PMID- 1602710 TI - Workplace fear of acquired immunodeficiency syndrome. PMID- 1602711 TI - Implementation of a one-hour fast-track service: one hospital's experience. PMID- 1602712 TI - An open letter to emergency nurses from an overdose patient. PMID- 1602713 TI - Trauma nursing record. PMID- 1602714 TI - Emergency department patient follow-up. PMID- 1602715 TI - Patients who leave without being seen. PMID- 1602717 TI - Intussusception in pediatric patients. PMID- 1602718 TI - Blood and breath alcohol testing. PMID- 1602716 TI - Interpreting your, er ... blood gases. PMID- 1602719 TI - The pregnant trauma patient: special considerations in emergency department care. PMID- 1602720 TI - A 31-year-old man with fever, sore throat, and difficulty swallowing. PMID- 1602721 TI - Profile of an English emergency nursing leader. Interview by Marlene Jezierski. PMID- 1602722 TI - Kennestone Hospital Emergency Center, Marietta, Georgia. PMID- 1602723 TI - View from the stretcher. PMID- 1602724 TI - [Clinical feature of the diabetic patients with recurrent pulmonary tuberculosis]. AB - We investigated the clinical feature of 22 diabetic patients diagnosed as having recurrent pulmonary tuberculosis. More than half of the patients relapsed within five years after discharge from the hospital. The mean serum albumin concentration of those patients who experienced relapses within three years was significantly lower than that of the patients who experienced relapses a period of time greater than three years. We recognized a significant negative correlation between the recurrent period and body mass index or fasting plasma glucose values. Among these patients, 50% of them ceased treatment for diabetes mellitus personally or had not been diagnosed as having diabetes mellitus before the relapse. All of the patients who ceased treatment for diabetes mellitus before readmission were able to obtain good plasma glucose control only through diet therapy during their first hospital admission for pulmonary tuberculosis. From this study, We concluded that strict plasma glucose control is important for the prevention of a relapse of the mycobacterial infection in patients with diabetes mellitus. PMID- 1602725 TI - [Surveillance of tuberculosis epidemics in Aichi Prefecture]. AB - A survey was done on the conditions of the tuberculosis surveillance system used for extraordinary examination in high tuberculosis prevalence areas in Aichi Prefecture during the period from 1981 to 1989. The results were as follows: 1) A total of 25 health centers provided information to 456 cases in specific groups known as "danger groups" and 227 cases within a furniture company. Information was most frequently provided when the index cases had been diagnosed bacillary positive. 2) Extraordinary examinations were performed on 222 cases for nine years, one case a year per each health center. The frequency of extraordinary examination was never high. A total of five epidemic cases (2.3%) and 30 microepidemic cases (13.5%) were discovered. 3) Coordination among health centers to make examinations was required in 81 cases (36.5%). 4) In index cases in which extraordinary examinations were performed, 43 preventable cases (19.4%) were found. It is therefore important to thoroughly enforce family-contact examinations. In order to complete extraordinary examinations, the importance of not only the systematic collection of information and the action of examination about specific groups but also the establishment of a surveillance system for extraordinary examinations is vital. PMID- 1602726 TI - [Analysis of chronic excretors of Mycobacterium bacilli in Aichi Prefecture]. AB - Among the patients diagnosed as having pulmonary tuberculosis who were newly admitted to six major tuberculosis centers in Aichi Prefecture during the period from January 1, 1982 to December 31, 1986, 73 patients were chronic excretors of Mycobacterium bacilli (chronics), whose sputum cultures tested positive at both 11 and 12 months after admission. In this study, those 73 patients were analyzed in March 1988. If the patient was still hospitalized at that time, the patient was re-evaluated six months later. The life table method was used for analysis of clinical procedures. For the analysis of risk factors for chronics, 37 patients who were treated after 1971 when RFP was available for treatment were used. The results in this study are as follows: 1. A total of 49.3% of the patients were determined chronics (those who had initial chemotherapy before 1970 when RFP was not available). This result suggests that the use of RFP may contribute to the reduction of chronics. 2. Patient delay in diagnosis, as well as irregular chemotherapy, was one of the factors for the development of chronics. 3. In the chronics, many patients showed severe findings in their chest X-rays, high bacillary counts in the sputum, and low drug-sensitivity bacilli when treated with the major anti-tuberculosis drugs. 4. The rate of chronics from newly admitted patients with positive sputum cultures following the initial chemotherapy treatment was 1.3%. This rate could increase following longer observation periods. 5. Chronics were more prevalent in patients with Type I (extensive cavitary type) findings in the chest X-rays, and positive sputum smears for Mycobacterium bacilli in the clinical findings when compared with all newly registered active tuberculosis patients during the same period in Aichi Prefecture. 6. Concerning the outcome, 55 patients were discharged (17 improved; 13 personally released; 25 deceased) while 18 remain hospitalized. Among those discharged patients, 17 patients were released as a result in improved health while 25 died. These results indicate poor prognosis. Using the life table method, the estimated mortality rate is 49.7%, and the negative sputum rate is 30.5% five years later. 7. Using a multivariate analysis on the prognosis, the risk factor was greatest for poor prognosis for those patients who had Type I findings in their chest X-rays, initial chemotherapy before 1970, complications, and that were male. 8. The patients with improved health, were more sensitive to the drugs applied when compared to the fatal patients. 9. Careful chemotherapy during the first two years may contribute to the reduction of chronics. PMID- 1602727 TI - [So-called "open healing" of chronic calcified pleural empyema--a study on the etiological and clinical problems]. AB - Surgery performed on a 70 year-old male revealed a case of chronic calcified pleural empyema open healing that was induced through an effective bronchiolar drainage mechanism. The patient had previously received anti-tuberculosis medication, including INH and RFP, 7 years prior for positive sputum cultures and symptoms of fistulation observed in an x-ray finding of right lung pleural calcification. The four cardinal signs of chronic calcified pleural empyema open healing are as follows: 1. Failure to isolate tubercle bacilli, 2. Inability to locate necrotic coagulation or specific inflammatory granulation tissue on the cavitary wall, 3. Calcified pleural plaque detached from the cavitary wall, and 4. Microscopic recognition of many drainage bronchiolar openings to the empyema and the inner surface of the empyema covered with stratified squamous epithelium, which possibly penetrated via the entering bronchioles. PMID- 1602728 TI - [New classification of endobronchial tuberculosis and balloon dilatation of bronchial stenosis]. AB - Endobronchial tuberculosis frequently leaves bronchial stenosis as the complication despite of modern efficacious chemotherapy, and it may be misdiagnosed as bronchial asthma or bronchogenic carcinoma. When bronchial stenosis involves major airway, its treatment needs such special measures as steroid therapy, surgical intervention and/or laser therapy, but the therapeutic result is often disappointing. We have introduced a new classification of endobronchial tuberculosis, analyzing bronchoscopic findings in 166 cases of endobronchial tuberculoses. Namely, endobronchial tuberculosis was classified into seven subtypes as stenotic type with fibrosis, stenotic type without fibrosis, actively caseating type, tumorous type, ulcerative type, granular type, and nonspecific bronchitic type. Actively caseating type (48 cases: 28.9%), stenotic type without fibrosis (44 cases: 26.5%), nonspecific bronchitic type (31 cases: 18.7%) and stenotic type with fibrosis (30 cases: 18.1%) were predominant in the order of frequency, but tumorous type (9 cases: 5.4%), ulcerative type (2 cases: 1.2%) and granular type (2 cases: 1.2%) were relatively uncommon. Stenotic type with or without fibrosis, actively caseating type and tumorous type of endobronchial tuberculosis were closely related to bronchial stenosis. In these cases, it is necessary to apply specific measures for preventing or minimizing bronchial stenosis. To consider the therapeutic effect of steroid on the alleviation of bronchial stenosis in endobronchial tuberculosis, it may be very effective when the interval between symptom-onset and treatment with steroid is less than 6 months. To exploit a new treatment modality for bronchial stenosis, balloon dilatation was also carried out in 12 patients with endobronchial tuberculosis. Under local anesthesia, 4F-Fogarty balloon was inserted via bronchofiberscope in ten cases and 10F-Gruentzig balloon was introduced under fluoroscopic guide in two others.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602729 TI - Communicable disease: the cycle continues. PMID- 1602730 TI - AIDS in Kansas. PMID- 1602731 TI - Tuberculosis in Kansas. PMID- 1602732 TI - Immunizations the most cost effective means of disease prevention: a state-local cooperative. PMID- 1602733 TI - AIDS dilemma: risk vs. responsibility in nursing care. PMID- 1602735 TI - [98th meeting of the German Society of Internal Medicine, Wiesbaden, 26-29 April 1992. Abstracts]. PMID- 1602734 TI - Rabies in Kansas, 1982-1991. PMID- 1602736 TI - Lipids, liposomes, and rational drug design. PMID- 1602737 TI - Efficacy of liposome-encapsulated indomethacin in response against metastatic 3LL and B16F1 tumor cells. AB - The ability of large liposomes to be taken up by tissue phagocytic cells, e.g., macrophages, has made it possible to increase the efficacy of several drugs as immunomodulating agents. In the present work, we have evaluated the effect of indomethacin, a prostaglandin synthesis inhibitor, both free and encapsulated in liposomes, on the spontaneous metastatic potential of 3LL and B16F1 tumor cells. Liposomes containing either carboxyfluorescein, indomethacin, or carboxyfluorescein plus indomethacin, were made in order to evaluate their in vitro plasma stability and in vivo clearance from the blood. The liposomes showed a high stability after 6 hours of plasma incubation and they were rapidly cleared in vivo. Liposomes encapsulating propidium iodide, a fluorescent DNA binding dye, were mainly taken up in vivo by hepatic and spleen macrophages 1 hour after intravenous injection, but not by lung macrophages. When C57BL/6 mice were intravenously inoculated with 10(5) 3LL or B16F1 tumor cells previously incubated with indomethacin (10(-7) M) for 48 hours, the number of experimental lung metastatic foci was increased with respect to their respective control groups. Also, in 3LL or B16F1 tumor-bearing mice, treatment with indomethacin (0.5 mg/kg weight/day) for 10 days enhanced the number of lung metastases, but not significantly. However, when mice received indomethacin encapsulated in liposomes, the number of metastases was significantly reduced. In addition, encapsulated indomethacin (0.5 mg/kg weight/day) inhibits prostaglandin E2 production by peritoneal and spleen macrophages, whereas no significant inhibitory effect was observed with control-liposomes or equivalent doses of free indomethacin. We conclude that intravenous administration of liposome encapsulated indomethacin has an antimetastatic effect on tumor-bearing mice. Use of indomethacin in liposomes may avoid the stimulation of metastases observed when the drug is administered alone. PMID- 1602738 TI - Localization of matrix metalloproteinase 3 (stromelysin) in osteoarthritic cartilage and synovium. AB - Degradation of proteoglycans is an initial change in osteoarthritic cartilage. Matrix metalloproteinase-3 (MMP-3; stromelysin) capable of degrading cartilage proteoglycans and type IX collagen was immunolocalized in osteoarthritic and normal cartilage. Immunohistochemical studies showed MMP-3 in chondrocytes of the superficial and transition zones in approximately 90% of osteoarthritic cartilage (60 of 67 samples) and in 31% of those of the superficial zone in some normal cartilage (4 of 13 samples). MMP-3 staining correlated directly with the histological histochemical scores of Mankin and with proteoglycan depletion, up to a certain grade of severity. Chondrocytes in the deep radial zone, clusters, and osteophytes were immunostained only when proteoglycan depletion and fissures affected them. Culture media from osteoarthritic cartilage contained significantly higher levels of metalloproteinase activity that was identified as MMP-3 by immunoblotting and lower amounts of tissue inhibitor of metalloproteinases compared with those in the control samples. MMP-3 was also immunolocalized in the lining cells of most osteoarthritic synovium (20 of 23 specimens, 87%) with a direct correlation with scores of inflammatory cell infiltration in the synovium, but it was not detected in the normal synovium. Light and electron microscopic studies demonstrated that MMP-3 digests proteoglycan aggregates in human articular cartilage. Treatment of normal and osteoarthritic cartilage slices with tumor necrosis factor-alpha and/or interleukin-1 alpha increased the number of MMP-3-immunoreactive chondrocytes and the intensity of the staining. These data suggest that MMP-3 produced by the chondrocytes and synovial lining cells under stimulation with these cytokines may be important in proteoglycan degradation in human ostoearthritic cartilage. PMID- 1602739 TI - Cysteine proteinase inhibitor in cultured human medullary thyroid carcinoma cells. AB - The TT cell line of human medullary thyroid carcinoma, that retains some of the differentiated functions of thyroid C cells including the synthesis and secretion of calcitonin, was found to contain and release into the culture medium cysteine proteinase inhibitor(s), cystatin(s). The major inhibitor, which is similar to, if not identical with, cystatin C, is constitutively released, or secreted, by TT cells. The rate of secretion of cystatin, quantified by titration of inhibition of papain, was stimulated by dibutyryladenosine 3':5'-cyclic monophosphate, forskolin, the calcium ionophore A 23187, and by the tumor promoter, 12-O tetradecanoylphorbol-13-acetate (TPA). Neither forskolin nor TPA had, however, an effect on the level of the inhibitor in TT cells. Treatment with n-butyrate strongly inhibited the proliferation of TT cells, and led, in 4 to 7 days, to a doubling of the intracellular concentration of cystatins. Northern blot hybridizations to a 32P-labeled riboprobe complementary to human cystatin C cDNA indicated that cAMP, forskolin, and TPA had no effect on the steady-state levels of cystatin C mRNA. These data indicate that release of cystatin(s) from TT cells is regulated by cAMP-calcium-protein kinase C mechanisms that appear to be similar to those that regulate the secretion of calcitonin from these cells. However, in contrast to the calcitonin gene, the expression of the cystatin C gene in these cells is not regulated by cAMP or TPA. By a combination of acetone fractionation, affinity chromatography on Cm-papain-Sepharose, and gel exclusion chromatography a protein of approximately 14 kilodaltons was isolated from TT cells that reacted with antibodies against human cystatin C, and strongly inhibited papain. Cystain secreted by TT cells also had a molecular weight of 14 kilodaltons, and reacted with anti-human cystatin C antibodies. The physiologic and pathologic roles of cystatins in different cell types remain to be established. The TT cells provide a suitable cell type to study the regulation of the expression of the cystatin gene and the mechanism of cystatin release. PMID- 1602740 TI - Human umbilical vein endothelial cell killing by activated neutrophils. Loss of sensitivity to injury is accompanied by decreased iron content during in vitro culture and is restored with exogenous iron. AB - First passage human umbilical vein endothelial cells (HUVECs) were sensitive to killing by activated neutrophils and reagent hydrogen peroxide (H2O2). Catalase and deferoxamine prevented killing whereas soybean trypsin inhibitor and superoxide dismutase did not. In these regards, HUVECs are similar to previously characterized endothelial cells from bovine and rat. Although first passage HUVECs were killed by activated neutrophils, sensitivity fell off rapidly as the cells were maintained in culture. At passage 2 (four population doublings), and beyond, HUVECs were highly resistant. The cells also became resistant to killing by reagent H2O2. The acquisition of resistance to killing was not accompanied by a failure to up-regulate neutrophil adhesion molecules or to support neutrophil adhesion. Levels of intracellular anti-oxidants (total thiols, though not glutathione, glutathione peroxidase or catalase activity) increased as a function of passage in culture. However, levels of glutathione and total thiols in late passage (resistant) HUVECs were similar to levels in late passage rat pulmonary artery endothelial cells, that were sensitive to killing by activated neutrophils. Cell-associated iron in HUVECs fell as a function of time in culture. By passage 2, the amount of total iron measurable with the Ferrozine reagent was only about 30% of the amount recovered from first passage HUVECs. The loss of iron from the cells may underlie much of the concomitant resistance to killing because when the cells were pretreated with iron under conditions in which it could be taken up, sensitivity to killing by activated neutrophils and by H2O2 was restored. PMID- 1602741 TI - Interferon-beta. A potential autocrine regulator of human vascular smooth muscle cell growth. AB - Positive and negative signals regulate the proliferation in vitro of vascular smooth muscle cells (SMC), a principle cell type in the blood vessel wall. Immune interferon (IFN-gamma, a type II IFN) retards the growth of human SMC, but the effect of type I IFN (IFN-alpha or beta) is unknown. Furthermore, the capacity of SMC to produce IFN is uncharacterized. If type I IFN alters SMC growth and is produced by this cell type, an autocrine inhibitory loop could operate in vascular growth control. To test this possibility, we compared the effects of IFN alpha, beta, and gamma on the growth of SMC stimulated by platelet-derived growth factor, interleukin-1 or tumor necrosis factor alpha. IFN-beta and IFN-gamma, but not IFN-alpha, consistently retarded growth of SMC cultures (measured by net DNA accumulation and cell number). We investigated whether SMC could produce IFN beta, a mediator characteristically produced by fibroblasts. Vascular SMC treated with poly(I):poly(C) or tumor necrosis factor-alpha expressed IFN-beta mRNA. SMC treated with poly(I):poly(C) or Newcastle Disease virus elaborated biologically active IFN-beta as well. Our results establish that IFN-beta inhibits human vascular SMC growth and that these cells can express the IFN-beta gene. These findings show that human vascular SMC have the capacity of producing a potential autocrine growth regulator. PMID- 1602742 TI - Centrosomes, microtubules, and microfilaments in the reendothelialization and remodeling of double-sided in vitro wounds. AB - The maintenance of endothelial monolayer integrity is an important function of aortic endothelial cells. Our study was designed to test two hypotheses related to the repair of the wounded endothelial monolayer. First, that the reappearance of the highly ordered cobblestone monolayer after wound closure is associated with specific sequential changes in the cytoskeletal system. Second, that there are different patterns of reendothelialization depending on whether microfilaments or microtubules are disrupted. One and a half millimeter wide wounds were created down the middle of confluent endothelial monolayers so that there were two wound edges facing each other. During the initiation of repair, the centrosomes of the cells on both sides of the wound reorientated to the front of the cell. The dense peripheral band of actin microfilaments disappeared, the cells elongated and migrated as a uniform sheet with wound closure occurring within 60 hours. The rate of closure remained constant until the migrating fronts met. The cytoskeletal changes observed and the rate of closure were similar to those we reported in a single edge wound. At closure, however, there was a transient piling up of cells which disappeared after 24 to 36 hours. Within 36 to 48 hours after closure, the centrosomes became randomly distributed around the nucleus. By 40 to 48 hours, the dense peripheral band started to reappear and the cells returned to a cobblestone appearance 72 to 96 hours after closure. Thus, the remodeling of the confluent monolayer after wound closure occurs in association with a specific series of cytoskeletal changes. When the microfilaments were disrupted with cytochalasin B, cell migration still occurred but it took up to four times longer for closure. These cells were initially flatter than normal and contained only a few microfilament fibers; however, the microtubule system was intact and centrosome reorientation occurred, but at a slower rate. However, when the microtubules were disrupted with colchicine, either at the onset of wounding or during repair, neither centrosome reorientation nor cell migration occurred. Thus wound closure of small-sized wounds require the presence of intact microtubules, whereas the additional presence of microfilaments results in a more rapid and efficient system of reendothelialzation. PMID- 1602743 TI - Defective expression of neurofilament protein subunits in hereditary hypotrophic axonopathy of quail. AB - Hereditary hypotrophic axonopathy is an inherited, neuronal cytoskeletal disease of the "quiver" mutant quail (Quv). Nerve tissue pathology is characterized by axonal hypotrophy associated with neurofilament (NF) deficiency in the central and peripheral nervous system. To elucidate the biochemical mechanism of this disease, we examined the in vivo expression of NF triplet protein subunits and the assembly state thereof in neuronal cell bodies in adult Quv and controls. Gel electrophoresis and Western blot analysis indicated that low, middle and high molecular mass NF subunits were markedly deficient in the brain, cervical spinal cord and sciatic nerve of Quv. Immunohistochemically, the spinal cord of Quv had no immunoreactive products corresponding to low molecular mass NF. However, middle and high molecular mass NF antisera stained few axons in the white matter and bound to ventral horn cell bodies, which in the controls were not labeled. Furthermore, a 130-kDa subunit likely to be a non- or hypophosphorylated form of middle molecular mass NF was localized in neuronal cell bodies with considerably stronger intensity than those in the controls. Ultrastructurally, intermediate filaments were not seen in such neurons; instead amorphous matrix was increased between clusters of granular endoplasmic reticulum and in the peripheral cytoplasmic areas. Degenerative changes of the neurons were very rare. We hypothesize that the deficiency of NFs in Quv results from an alteration of filament assembly caused by defective expression of low molecular mass NF. This mutant presents direct evidence for the importance of NFs in achieving and/or maintaining normal axon caliber and provides a novel system for further studies on NF expression, metabolism and function. PMID- 1602744 TI - Acute simian varicella infection. Clinical, laboratory, pathologic, and virologic features. AB - Five African green monkeys inoculated intratracheally with 7.5 x 10(3) to 1.4 x 10(5) plaque-forming units of simian varicella virus (SVV) were subjected to clinical, laboratory, pathologic, and virologic analyses to study the pathogenesis of acute varicella. All animals developed viremia and rash and were sacrificed 8 to 11 days post-infection. No serum was available for postmortem serologic studies. Examination of multiple organs for pathologic changes and for SVV-specific antigen and nucleic acid revealed inflammation, hemorrhagic necrosis, and intranuclear Cowdry A inclusions in liver, lung, lymph node, and spleen; mild inflammation without necrosis in adrenal gland, kidney, and bone marrow, and SVV-specific antigen and nucleic acids in all viscera examined. No pathologic changes, SVV antigen or nucleic acids were detected in the spinal cord or in the brain from any of the monkeys. Ganglia revealed mild inflammation but no necrosis, and intranuclear inclusion bodies in non-neuronal cells of one trigeminal ganglion; SVV antigen and nucleic acids were detected in both non neuronal and neuronal cells in ganglia. The pathologic and virologic findings in viscera are consistent with those described in viscera of humans with disseminated zoster, but the mild inflammatory changes in ganglia during acute simian varicella infection contrast with the extensive hemorrhagic necrosis and intranuclear inclusion bodies seen in human ganglia after disseminated varicella or zoster. Nevertheless, these studies show that ganglia become infected with varicella virus during primary infection, although the route of primary ganglionic infection remains to be determined, and indicate the possible usefulness of the SVV model to study varicella pathogenesis in humans. PMID- 1602746 TI - Special issue: medical and surgical management of epilepsy. PMID- 1602745 TI - Serum amyloid A changes high density lipoprotein's cellular affinity. A clue to serum amyloid A's principal function. AB - The affinity of high density lipoproteins (HDL), or HDL carrying serum amyloid A (HDL/SAA), for hepatocytes or peritoneal macrophages was examined, as part of an investigation exploring the principal function of SAA and how this may be related to amyloidogenesis. The binding results in conjunction with SAA's existence primarily on HDL during inflammation, and HDL's known "reverse cholesterol transport" function suggest a clear role for SAA in the afferent arm of the reverse cholesterol transport pathway during the process of inflammation. The presence of SAA reduced HDL's affinity for normal hepatocytes by a factor of 2. In contrast, HDL/SAA had a 3- to 4-fold higher affinity for macrophages than HDL alone. Furthermore, the number of binding sites for HDL/SAA increased on macrophages during inflammation, while decreasing on hepatocytes. The net effect was a significant shift in HDL cholesterol carrying capacity towards the macrophage. Competition experiments demonstrated that HDL/SAA is only half as effective as HDL in inhibiting radiolabeled HDL binding to macrophages. This is in keeping with the reduced apolipoprotein A-1 content in HDL/SAA. Strikingly, although HDL contains twice as much apolipoprotein A-1 as HDL/SAA, it is only one tenth as effective as HDL/SAA in inhibiting radiolabeled HDL/SAA binding to macrophages. The latter results suggest that there is a specific SAA binding site on macrophages. PMID- 1602747 TI - Classification of the epilepsies. PMID- 1602748 TI - Current strategies in the medical management of epilepsy. AB - Epilepsy is a fascinating disorder reflective of ongoing brain activity which at times is disordered. There have been significant advances in the understanding of the pharmacology of antiepileptic drugs such that effective treatment is feasible. Understanding the epilepsies and the phenomena of epileptic seizures will permit one to successfully deal with the major issues around these syndromes and lead to a very rewarding outcome. PMID- 1602749 TI - Intensive neurodiagnostic monitoring. AB - Intensive neurodiagnostic monitoring is useful in the diagnosis and classification of epileptic seizures and other paroxysmal disorders. The correlation of clinical/behavioral data, EEG events, and serum prolactin levels may clarify the type(s) of epileptic seizures and may distinguish epileptic seizures from non-epileptic events. Serial determinations of AED's may assist in the detection of problems with AED compliance and with drug interactions which complicate the patient's management. PMID- 1602750 TI - Surgical management of epilepsy: invasive monitoring and temporal lobectomy. PMID- 1602751 TI - Hemispherectomy, callostomy, and frontal lobectomy for seizures. PMID- 1602753 TI - Surgery for epilepsy in children. PMID- 1602752 TI - Childhood epilepsy: an overview. PMID- 1602754 TI - The patient with epilepsy--a nursing perspective. PMID- 1602755 TI - Fits and starts: diagnostic dilemmas in epilepsy. PMID- 1602756 TI - A report of cerebral surgery and its curative effect in a case of traumatic epilepsy by W.H. Nardin, M.D. PMID- 1602757 TI - Finite element stress analysis of a push-out test. Part II: Free interface with nonlinear friction properties. AB - In this second part of a two-part paper, nonlinear frictional properties measured at the bone/porous-surfaced metal interface are used to perform the stress analysis of a push-out test assuming free interface. In this case, the friction at the interface is the only mechanism to resist the externally applied load. Similar to the part I, the model is axisymmetric and consists of two cylinders in contact with each other through the interface. Various relative material properties and boundary conditions are simulated in order to examine their effects on the interface stresses and overall push-out resistance. The role of the force-fit and the load direction (push-out versus pull-out) on the results is also investigated. The computed radial and shear stresses are found to markedly vary both with location along the interface and with the testing configuration. The ultimate push-out resistance is also found to significantly alter as the material arrangement and boundary conditions change. The predicted push-out load augments with an increase in the force-fit and diminishes to nil in the absence of a press-fit. For the cases studied here, there is a relative difference of as large as 13 percent between the push-out response and the pull-out response so far as the interface stresses and the maximum resistance are concerned. Therefore, any comparison between the results of push-out (or pull-out) tests performed with different design configurations appears to be invalid. PMID- 1602758 TI - The isometric action of the forearm muscles. AB - The isometric forces and moments generated at the hand segment by thirteen of the forearm muscles were measured on three test subjects. Small bipolar surface electrodes were used to activate each muscle separately. The direction of the force vector generated at the fingertips and the percentage torque generated about the longitudinal axis of the hand segment were measured and were modeled for one subject as a parabolic function of the position of the wrist and radioulnar joints in their ranges of motion. The results exhibited a high standard deviation. It is proposed that a significant component of this standard deviation is inherent in the biomechanics of the musculo-skeletal system. Variations in the test protocol were used to test this hypothesis. The standard deviation was found to be significantly larger in the flexor muscles than the extensors. It was concluded that the stability and elasticity of the soft tissue structures in the region of the wrist joint may significantly influence the direction of the generated joint moment vector. PMID- 1602760 TI - Cracks emanating from slipping inclusions near a bone-implant interface. AB - It has been hypothesized that mechanical fracture at the bone-cement-implant interface is the initial cause for loosening of orthopedic implants. Previous investigators have observed cracks to emanate from methacrylate beads, apparently acting as inclusions within the cement. It is believed that the bond between these inclusions and the surrounding matrix breaks prior to emanation of radial cracks from the inclusion. An analytical model is developed for radial cracks emanating from circular inclusions that allow slip along their interface. The solution to the interaction of a single dislocation and a slipping inclusion is used as a Green's Function to model the crack. The Mode I stress intensity factors are calculated for arbitrary orientations of the crack and for varying relative stiffness of the matrix and the inclusion to test feasibility of crack growth. PMID- 1602759 TI - Theoretical analysis of an implantable force transducer for tendon and ligament structures. AB - A mathematical model was developed for an implantable force transducer to be inserted within the midsubstance of a ligament or tendon. The model was generated by performing both equilibrium and strain-displacement analyses on a metallic, curved beam structure placed within a parallel-fibered tissue. The analysis permitted the transverse pressure acting between the device and fibers to be calculated along with peak device strain and sensitivity (ratio of strain output to axial tissue force). Transducer pressure and transducer strain were expressed in terms of nondimensionalized design factors. A parametric analysis of the key design factors was then performed. The transverse pressure was shown to vary little for large changes in these factors whereas device strain changed markedly. The analysis was verified by a bench test on an example device. Such a model permits a proposed design to be evaluated without having to conduct costly experiments. PMID- 1602761 TI - Characterization of collagen fiber architecture in the canine diaphragmatic central tendon. AB - The diaphragmatic central tendon (DCT), a collagenous soft tissue membrane, acts as a mechanical buffer between the costal and crural muscles. Its direction of mechanical anisotropy has been shown to correspond to the collagen fiber preferred directions. These preferred directions were determined by gross histological examination, and were thus qualitative. In this work we quantified the collagen fiber architecture throughout the DCT using small angle light scattering (SALS). Helium-Neon laser light was passed through tendon specimens and the resultant scattered light distribution, which characterized the local collagen fiber architecture, was recorded with a linear array of five photodiodes. Throughout the DCT two distinct collagen fiber populations were consistently found. For each population three parameters were determined: 1) the preferred directions of collagen fibers, 2) the volume fraction (Vf) of fibers, 3) OI, an orientation index, which ranges from 0 percent for a random network to 100 percent for a perfectly oriented network. Vector maps were used to display results from 1) and 2), and showed a primary group (G1) going from the crural to costal muscles and a secondary one (G2) running perpendicular to G1. Comparisons of Vf between G1 and G2 showed that G1 contained about three times as many fibers as G2, a ratio similar to that found for the degree of mechanical anisotropy. OI were found to be about 60 percent, indicating a high degree of orientation, with no significant regional or population differences (p less than 0.05). These quantitative results suggest that throughout the DCT the degree of mechanical anisotropy is controlled exclusively by Vf. PMID- 1602762 TI - A finite element analysis of the indentation stress-relaxation response of linear biphasic articular cartilage. AB - The indentation problem of a thin layer of hydrated soft tissue such as cartilage or meniscus by a circular plane-ended indenter is investigated. The tissue is represented by a biphasic continuum model consisting of a solid phase (collagen and proteoglycan) and a fluid phase (interstitial water). A finite element formulation of the linear biphasic continuum equations is used to solve an axisymmetric approximation of the indentation problem. We consider stress relaxation problems for which analytic solution is intractable; where the indenter is impermeable (solid) and/or when the interface between the indenter and tissue is perfectly adhesive. Thicknesses corresponding to a thin and thick specimen are considered to examine the effects of tissue thickness. The different flow, pressure, stress and strain fields which are predicted within the tissue, over time periods typically used in the mechanical testing of soft tissues, will be presented. Results are compared with the case of a porous free-draining indenter with a perfectly lubricated tissue-indenter interface, for which an analytic solution is available, to show the effects of friction at the tissue indenter interface, and the effects of an impermeable indenter. While these effects are present for both thin and thick tissues, they are shown to be more significant for the thin tissue. We also examine the effects of the stiffness of the subchondral bone on the response of the soft tissue and demonstrate that the subchondral bone substrate can be modeled as a rigid, impermeable boundary. The effects of a curved tissue-subchondral bone interface, and the early time response are also studied. For physiologically reasonable levels of curvature, we will show that the curved tissue-subchrondal bone interface has negligible influence on the tissue response away from the interface. In addition, the short time stress-relaxation responses of the tissue (e.g., at times less than 1s) demonstrate the essential role of the fluid phase in supporting the load applied to the tissue, and by extrapolation to shorter times characteristics of normal joint motion, suggest the essential role of a biphasic model in representing soft tissue behavior in joint response. PMID- 1602763 TI - Strip extensiometry for comparison of the mechanical response of bovine, rabbit, and human corneas. AB - Specimens of bovine, rabbit, and human corneas were systematically tested in uniaxial tension to experimentally determine their effective nonlinear stress strain relations, and hysteresis. Cyclic tensile tests were performed over the physiologic load range of the cornea, up to a maximum of 10 percent strain beyond slack strain. Dimensional changes to corneal test specimens, due to varying laboratory environmental conditions, were also assessed. The measured stress strain data was found to closely fit exponential power function relations typical of collagenous tissues when appropriate account was taken of specimen slack strain. These constitutive relations are very similar for rabbit, human and bovine corneas; there was no significant difference between the species after preconditioning by one cycle. The uniaxial stress strain curves for all species behave similarly in that their tangent moduli increase at high loads and decrease at low loads as a function of cycling. In the bovine and rabbit data, there is a general trend towards more elastic behavior from the first to second cycles, but there is little variation in these parameters from the second to third cycles. In comparison, the human data demonstrates relatively little change between cycles. Increases in width of corneal test specimens, up to a maximum of 2 percent were found to occur under 95 percent relative humidity test conditions over 10 minutes elapsed time test periods, while specimens which were exposed to normal laboratory conditions (45 percent RH) were found to shrink in width up to a maximum of 9.5 percent over the same elapsed time period. The thickness of the test specimens were observed to decrease by 3 percent in 95 percent relative humidity and by 12 percent in 45 percent relative humidity over the same elapsed time period. PMID- 1602764 TI - Influence of bifurcations on forced oscillations in an airway model. AB - Forced oscillations is a technique to determine respiratory input impedance from small amplitude sinusoidal pressure excursions introduced at the airway opening. Models used to predict respiratory input impedance typically ignore the direct effect of bifurcations on the flow, and treat airway branches as individual straight tubes placed appropriately in parallel and series. The flow within the individual tubes is assumed equivalent to that which would occur in infinitely long tubes. In this study we examined the influence of bifurcations on impedance for conditions of the forced oscillatory technique. We measured input impedance using forced oscillations in straight tubes and in an anatomically-relevant, four generation physical model of a human airway network. The input impedance measured experimentally compared well to that obtained theoretically using model predictions. The predictive scheme was based on appropriate parallel and series combinations of theoretically computed individual tube impedances, which were computed from solutions to oscillatory flow of a compressible gas in an infinitely long rigid tube. The agreement between experimental measurements and predictions indicates that bifurcations play a relatively minor direct role on the flow impedance for conditions of the forced oscillations technique. These results are explained in terms of the small tidal volumes used, whereby the axial distance traveled by a fluid particle during an oscillation cycle is appreciably smaller than branch segment lengths. Accordingly, only a small fraction of fluid particles travel through the bifurcation region, and the remainder experience an environment approaching flow in an infinite straight tube. The relevance of the study to the prediction of impedances in the human lung during forced oscillations is discussed. PMID- 1602765 TI - A lumped parameter mathematical model of the splanchnic circulation. AB - A lumped parameter mathematical model to describe the propulsion of blood in the splanchnic circulation was developed by integrating the principles of mechanics and physiology. A set of governing equations by derived by specifically considering the contractility of the portal vein, hepatic vein, liver sinusoids, and of the draining lymphatics. These equations were then simulated on a computer. The present simulation results substantiate previous experimental observations that hepatic venous pressure leads to portal hypertension and increased liver interstitial fluid volume. PMID- 1602766 TI - Analysis of oxygen exchange between arterioles and surrounding capillary-perfused tissue. AB - A theoretical model is used to analyze oxygen transport in a three-dimensional tissue region containing an arteriole surrounded by an array of capillaries in planes perpendicular to the arteriole. Convective removal of oxygen from the vicinity of the arteriole by nearby capillaries is shown to increase diffusive oxygen loss from the arteriole. This effect depends on the locations of the capillaries, particularly those nearest to the arteriole. The arteriolar oxygen efflux is comparable to that predicted by a previous model which used a continuum approach, but the efflux does not increase with increasing perfusion as rapidly as predicted by the continuum model. Even a small capillary flow rate strongly influences the oxygen field surrounding the arteriole. PMID- 1602767 TI - Flow measurements in a highly curved atherosclerotic coronary artery cast of man. AB - Flow visualization and wall pressure measurements were made in a polyurethane cast of a cadaver coronary artery with a significant "s" shaped reverse curvature. A sucrose solution was used to simulate the kinematic viscosity of blood, with flow rates in the physiologic range. Flow visualization demonstrated significant secondary flow patterns in the wall vicinity, which increased with increasing Reynolds number. Random dye dispersion was observed at a Reynolds number of about 400, but not at 200. Dye filament patterns in the transition between the first and second curved region were predominantly influenced by the second curved region at lower Reynolds numbers, and by the first curved region at higher Re. Local wall pressure measurements demonstrated a significant centrifugal effect with large radial pressure differences across the casting. Flow resistances for the casting were considerably greater than reference Poiseuille flow values, and increased further with pulsatile flow. PMID- 1602768 TI - Thermal injury kinetics in electrical trauma. AB - The distribution of electrical current and the resultant Joule heating in tissues of the human upper extremity for a worst-case hand-to-hand high-voltage electrical shock was modelled by solving the Bioheat equation using the finite element method. The model of the upper extremity included skin, fat, skeletal muscle, and bone. The parameter sets for these tissues included specific thermal and electrical properties and their respective tissue blood flow rates. The extent of heat mediated cellular injury was estimated by using a damage rate equation based on a single energy barrier chemical reaction model. No cellular injury was assumed to occur for temperatures less than 42 degrees C. This model was solved for the duration of Joule heating required to produce membrane damage in cells, termed the lethal time (of contact) for injury. LT's were determined for contact voltages ranging from 5 to 20 kV. For a 10,000 volt electrical shock LT's for skeletal muscle are predicted to be: 0.5 second in the distal forearm, 1.1 second in the mid-forearm, 1.2 second in the proximal elbow, and 2.0 seconds in the mid-arm. This analysis of the electrical shock provides useful insight into the mechanisms of resultant tissue damage and provides important performance guidelines for the development of safety devices. PMID- 1602769 TI - Thermal modeling of polymerizing polymethylmethacrylate, considering temperature dependent heat generation. AB - A methodology for the modeling of unsteady heat conduction in polymethylmethacrylate (PMMA) during its exothermic polymerization is presented. The emphasis is on the formulation of a model for the volumetric rate of heat generation, including its temperature-dependent characteristics. Three parameters appear in the proposed model. The empirical determination of these parameters using Differential Scanning Calorimetry is demonstrated. The incorporation of the proposed model into finite volume methods is also demonstrated, in the context of unsteady, one-dimensional, radial heat conduction in cylindrical coordinates. In addition, the application of the proposed model to two test problems is presented and discussed. The results are encouraging, and the proposed methodology appears to be applicable to the thermal modeling of exothermic polymerization processes in general. PMID- 1602770 TI - Errors in simulated vertebral motions using Cardan Euler angles with a least squares method. PMID- 1602771 TI - Hemodynamic aspects of obliterative processes in peripheral blood vessel--rigid and soft narrowing. AB - Hemodynamic aspects of obliterative processes in peripheral blood vessels were studied on a mechanical model built of distensible tubing, with a fixed peripheral resistance, through which citrated blood was circulated by pulsatile flow. Hemodynamics of progressive focal stenosis, elongated soft stenosis, and elongated rigid stenosis were assessed. By the use of a hydrodynamic model and a series of in vitro experiments, we have measured the pressure and flow characteristics, and calculated the pressure and energy losses for the various stenotic sites. The critical stricture was found to be larger for a rigid stenosis than a soft stenosis. The length of the stenosis was also an important factor. Increasing the length of a rigid stenosis, for example, by 50 percent resulted in an increase of 25 percent in the flow through the stenosis. The energy dissipation was determined as a preferred indication for several parameters such as: pressure drop, pulsed flow, pulse rate, and the geometry and mechanical properties of the stenosis. PMID- 1602772 TI - Sensitivity of muscle force estimations to changes in muscle input parameters using nonlinear optimization approaches. AB - The purpose of this study was to analyze the sensitivity of muscle force calculations to changes in muscle input parameters. Force sharing between two synergistic muscles was derived analytically for a one-degree-of-freedom system using three nonlinear optimization approaches. Changes in input parameters that are within normal anatomical variations often caused changes in muscular forces exceeding 100 percent. These results indicate that errors in muscle force calculations may depend as much on inadequate muscle input parameters as they may on the choice of the objective and constraint functions of the optimization approach. PMID- 1602773 TI - Steroid/Thyroid Receptor Gene Super Family. Keystone Symposia on Molecular and Cellular Biology. February 21-27, 1992. Abstracts. PMID- 1602774 TI - Cell Biology of Virus Entry, Replication and Pathogenesis. Keystone Symposia on Molecular and Cellular Biology. February 28-March 5, 1992. Abstracts. PMID- 1602775 TI - Recognition of Endotoxin in Biologic Systems. Keystone Symposia on Molecular and Cellular Biology. March 1-7, 1992. Abstracts. PMID- 1602776 TI - Hematopoiesis. Keystone Symposia on Molecular and Cellular Biology. February 27 March 5, 1992. Abstracts. PMID- 1602777 TI - Charting the chart--an exercise in interpretation(s). PMID- 1602778 TI - To build a case: medical histories as traditions in conflict. PMID- 1602779 TI - "A case of amyotrophic lateral sclerosis": a reprise and reply. PMID- 1602780 TI - The politics of narrative form. PMID- 1602781 TI - Remaking the case. PMID- 1602783 TI - "Is there a person in this case?". PMID- 1602784 TI - Development of the physician's narrative voice in the medical case history. PMID- 1602785 TI - Winged words and chief complaints: medical case histories and the Parry-Lord oral formulaic tradition. PMID- 1602786 TI - Dek-can rearrangement in translocation (6;9)(p23;q34). AB - The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated and diagnosis at the DNA-level became an additional option. Both the dek gene on chromosome 6 and the can gene on chromosome 9 contain one specific intron where breakpoints of t(6;9) patients were found to cluster. The translocation results in a consistent chimeric dek-can mRNA which is generated from the 6p- derivative. Five centers participated in a study to estimate the incidence of t(6;9) in leukemic patients using conventional Southern blot analysis. Patients (n = 320) with either acute undifferentiated leukemia (AUL), AML, MDS or acute lymphoblastic leukemia (ALL) were screened for rearrangement of the genes involved in this translocation. Four of these 320 patients showed rearrangement of the can gene on chromosome 9, of which one also had a rearranged dek gene on chromosome 6. A further 20 patients were studied with karyotypic aberrations in which either the short arm of chromosome 6 or the long arm of chromosome 9 were specifically involved. Both conventional Southern blot analysis and contour-clamped homogeneous electric field (CHEF) analysis failed to show dek-can rearrangement in any of these patients. The results of our study indicate that the incidence of the t(6;9) is a low as reported based on cytogenetic data and that rearrangement of the dek and can genes is mainly restricted to this specific translocation. PMID- 1602787 TI - Monitoring of residual disease in chronic myelogenous leukemia by quantitative polymerase chain reaction. AB - The polymerase chain reaction (PCR) has become a standard method for highly sensitive detection of the bcr/abl rearrangement in patients with chronic myelogenous leukemia (CML) or acute lymphoblastic leukemia (ALL). The exquisite sensitivity of the PCR facilitates the detection of residual leukemic cells after chemotherapy or after bone marrow transplantation. However, the detection of minimal residual disease does not yield any information on the malignant potential of the bcr/abl-rearranged cells. Qualitative PCR is therefore of limited prognostic value in the monitoring of residual leukemia. We have adapted the PCR for quantitative evaluation of cells carrying the bcr/abl rearrangement and by means of two exemplary cases of CML patients after bone marrow transplantation and under treatment with alpha-interferon, respectively, we show that this new technique is suitable for the long term follow-up of the activity of the residual bcr/abl rearranged clone. Longitudinal monitoring of residual disease by the technique presented provides a novel tool for detection of incipient relapse at a very early stage. PMID- 1602788 TI - Cytogenetics for detection of minimal residual disease in acute myeloblastic leukemia. AB - Bone marrow samples collected from acute myeloblastic leukemia (AML) patients in complete clinical and hematological remission were studied for the persistence of cytogenetic abnormalities. AML patients from the three favorable cytogenetic categories [inv 16, t(8;21) and t(15;17)] and patients from the unfavorable cytogenetic categories (+8, -5, -7 and Philadelphia-positive) were studied. Seventy-one patients had evaluable metaphase spreads in remission marrows and 20 (28%) had one or more abnormal metaphases identical to that present in the pretreatment marrow. All 20 of these patients relapsed within 78 weeks, thus there were no false positive studies. Fifty-one patients had only diploid metaphases in their complete remission marrow, 25 relapsed, and 21 remained in continuous complete remission. Thus there was a 49% false negative rate of this study. These data indicate that the failure to detect residual chromosomally abnormal cells in the bone marrow does not guarantee continuous complete remission. Cytogenetic study was most useful in the favorable cytogenetic groups and least useful in the unfavorable groups. The persistence of normal metaphases in pretreatment marrows did not affect outcome or risk of recurrence. Twenty-five of 34 evaluable patients who relapsed after remission had either the identical cytogenetic abnormality present in the pretreatment marrow or showed the identical abnormality with additional chromosomal changes. Thus study indicates that cytogenetic examinations of complete remission bone marrow samples in patients with AML provides an objective method for detecting residual leukemia, and identifies patients with a potential for prolonged disease-free survival. PMID- 1602789 TI - Minimal residual disease status in transplanted chronic myelogenous leukemia patients: low incidence of polymerase chain reaction positive cases among 48 long disease-free subjects who received unmanipulated allogeneic bone marrow transplants. AB - Forty-eight long-term disease-free chronic myelogenous leukemia (CML) patients, who had received unmanipulated allogeneic bone marrow transplants (BMT) for eradication of the Philadelphia (Ph1)-positive clone were studied by polymerase chain reaction (PCR), using a very sensitive PCR procedure and very stringent criteria for preventing and revealing contamination. Nine patients (18%) were positive at the first PCR examination, but only one patient remained PCR positive four years after. However, a second PCR analysis performed on new bone marrow samples obtained at a median interval of 14 months (range 6-16) after the first specimen collection from six of nine originally positive cases, and from 16 of 39 originally negative cases, showed that only one of the six positive cases remained positive, whereas negativity was confirmed in all the originally negative patients. These data are evidence that the Ph1-positive clone is apparently completely eradicated in the majority of CML patients who survive disease-free long-term after an unmanipulated allogeneic BMT and that only sporadic cases remain PCR-positive four years post-BMT. The data also show that at least two sequential bone marrow samples for each patient must be analyzed before drawing conclusions regarding the stable persistence of BCR/ABL transcripts and the minimal residual disease status. PMID- 1602790 TI - Translocation t(9;11)(p21;q23) in pediatric de novo and secondary acute myeloblastic leukemia. AB - The t(9;11)(p21;q23) has been associated with characteristic clinical features and a superior treatment outcome in previously untreated pediatric acute myeloblastic leukemia (AML), but has not been well studied in children with secondary AML. This translocation was detected in 6.7% of de novo and 46% of secondary AML patients treated at St Jude Children's Research Hospital over an 11 year period. Clinical, immunophenotypic, and morphologic characteristics were examined for the cases of t(9;11) secondary AML (n = 12) and compared with findings for children with t(9;11) de novo AML (n = 12). Patients with t(9;11) secondary AML were older at diagnosis, had higher hemoglobin levels, and central nervous system leukemia or hepatosplenomegaly was less frequent. These differences probably reflect survival of the first malignancy and close clinical scrutiny during post-treatment follow-up. Whereas the t(9;11)(p21;q23) occurred exclusively in the French-American-British (FAB) M5 subtype in de novo AML, the FAB M0 and M4 subtypes were also represented in secondary cases. The complete remission rate was somewhat higher for the de novo AML group (91 vs 58%; p = 0.16); their event-free survival was clearly superior to that for children with t(9;11) secondary AML (p = 0.003). Host differences related to the previous malignancy or its treatment could explain the poorer clinical outcome for patients with t(9;11) secondary AML. Alternatively, there could be critical differences at the translocation site or additional, hidden molecular events, that explain the different outcomes. PMID- 1602791 TI - Hexamethylene bisacetamide in myelodysplastic syndrome: effect of five-day exposure to maximal therapeutic concentrations. AB - The efficacy of hexamethylene bisacetamide (HMBA), a potent polar-planar solvent which is capable of differentiating leukemias and solid tumors in vitro at clinically achievable concentrations, was studied in 16 patients with severe myelodysplastic syndromes (MDS). An adaptive control dosing algorithm was used to maintain HMBA steady-state concentrations (Css) within a narrow therapeutic window (1-2 mM) for five days every four weeks. Despite achieving the target HMBA Css during at least two courses in each of 15 patients, HMBA did not produce clinically relevant improvements in blood cell counts nor in other functional indices. Instead, HMBA induced cytopenias in the majority of these patients, most of whom had preexisting cytopenias and limited hematopoietic reserves. These disappointing results correlated with concurrent in vitro bone marrow studies from these patients in which both the HMBA concentrations that were optimal for differentiation in vitro (2-5 mM) and the HMBA Css that were achieved in this study (1-2 mM) substantially inhibited the growth of granulocyte-macrophage colony-forming units and erythroid burst-forming units. Although the mechanism responsible for the anti-proliferative effects of HMBA on hematopoietic progenitors (cytotoxicity versus terminal differentiation) could not be determined, the induction of cytopenias and lack of significant clinical improvements suggest that HMBA is cytotoxic and will not be useful alone as a differentiating agent on this schedule of administration in the treatment of MDS. PMID- 1602792 TI - Childhood acute lymphoblastic leukemia with both t(1;19) and t(9;22). AB - The chromosomal rearrangements t(1;19)(q23;p13.3) and t(9;22) (q34;q11.2) are independent abnormalities commonly observed in the blast cells of children with acute lymphoblastic leukemia (ALL). We report three children whose leukemic cells contained both translocations at diagnosis. The patients, two males aged 3 and 8 years and a female aged 14 years, all presented with central nervous system involvement. One patient exhibited a pre-B leukemic phenotype (cytoplasmic immunoglobulin, cIg, positive), while two had an early pre-B phenotype (cIg negative). All three patients received radiotherapy and multiagent chemotherapy which included an epipodophyllotoxin in two patients. Two patients suffered relapses of ALL, in both cases with disappearance of t(1;19)-containing clones but persistence of t(9;22). The two patients who received an epipodophyllotoxin as part of their chemotherapeutic regimen both developed secondary myeloid leukemia with entirely new cytogenetic findings, including abnormalities of chromosome band 11q23. These patients are the first to be described with this unusual combination of cytogenetic abnormalities. PMID- 1602793 TI - Different patterns of relapse associated with three intensive treatment regimens for pediatric E-rosette positive T-cell leukemia: a Pediatric Oncology Group study. AB - One hundred and ninety-three children with T-cell acute lymphocytic leukemia (T ALL) whose leukemia cells were E-rosette positive were treated on a Pediatric Oncology Group study (1979-1986) designed specifically for patients with T-ALL. The results of modified LSA2L2 therapy with or without intensified intrathecal chemotherapy and cranial irradiation (radiotherapy) were compared with those obtained using a simpler multi-agent protocol which included radiotherapy (T-cell 2). The complete remission (approximately 90%) and 3-year event-free survival rates (approximately 40%) were similar in the three treatment groups. However, the pattern of extramedullary relapse varied according to specific treatment regimen. Patients who received LSA2L2 therapy with less intensive intrathecal chemotherapy and no radiotherapy had a central nervous system (CNS) relapse rate (i.e. isolated CNS +/- other site) of over 20%, compared to only 10% for patients receiving the same systemic chemotherapy with intensified intrathecal therapy and radiotherapy, and less than 5% for those receiving T-cell 2 therapy. In contrast, males receiving T-cell 2 therapy had a testicular relapse rate of greater than 20% compared to less than 10% for patients receiving either regimen (i.e. +/- intensified intrathecal chemotherapy and radiotherapy) of modified LSA2L2 therapy. We conclude that, in the context of these therapies, central nervous system irradiation plus intensive triple (hydrocortisone, methotrexate, cytarabine) intrathecal chemotherapy is more effective than CNS preventative therapy comprised of intrathecal low-dose methotrexate only, and that the more complex multi-agent chemotherapy used in the modified LSA2L2 regimens appeared to be more effective in prevention of testicular leukemia, indicating that the effectiveness of sanctuary site treatment was therapy-specific. PMID- 1602794 TI - Rearrangement of BCR genes in malignant lymphoma. AB - The Philadelphia chromosome, originally thought to be associated solely with chronic myelogenous leukemia (CML), has since been identified in acute leukemias and in some cases of lymphoma. The Philadelphia chromosome results from reciprocal translocation of genetic material between chromosome 9 and 22 involving the c-abl and BCR genes respectively. Southern blot analysis of the BCR genes was carried out on biopsy specimens from 49 patients presenting with malignant lymphoma without a previously documented CML phase. In two patients, BCR gene rearrangements were detected in the malignant lymph nodes but not in the bone marrow samples. A third patient showed BCR gene rearrangements in the bone marrow but not in the lymph node. From this limited study, it seems that the overall incidence of BCR gene rearrangement in malignant lymphoma is similar to that observed in adult AML. PMID- 1602795 TI - Intracellular cytosine arabinoside accumulation and cytosine arabinoside triphosphate formation in leukemic blast cells is inhibited by etoposide and teniposide. AB - Cytosine arabinoside (ara-C) is one of the most active compounds in the treatment of acute leukemias. In the majority of current protocols ara-C is combined with other cytotoxic agents in an attempt to increase antileukemic activity. The present study investigated the impact of etoposide, teniposide, amsacrine, mitoxantrone, anthracyclines, and asparaginase on the cellular accumulation of ara-C and its intracellular metabolism in order to provide a better rationale for combination therapy. Intracellular accumulation and phosphorylation of ara-C were determined in peripheral blast cells from twenty patients with acute leukemias after exposure to 1 and 10 mumol/l ara-C alone and after preincubation with 1 and 10 micrograms/ml etoposide, 10 and 100 micrograms/ml teniposide, 10 mumol/l amsacrine, 500 ng/ml mitoxantrone (or daunorubicin or doxorubicin) or 10 mumol/l asparaginase. Ara-C accumulation at 10 mumol/l was decreased by 1 microgram/ml etoposide (67 +/- 18% of control), 10 micrograms/ml etoposide (30 +/- 22%), 10 micrograms/ml teniposide (12 +/- 23%), 100 micrograms/ml teniposide (10 +/- 18%), and amsacrine (51 +/- 21%). Intracellular ara-CTP formation was determined at an extracellular concentration of 10 mumol/l and preincubation with these drugs. The intracellular formation of ara-CTP was decreased by 1 microgram/ml etoposide (77 +/- 15% of control), 10 micrograms/ml etoposide (32 +/- 22%), 10 micrograms/ml teniposide (10 +/- 9%), 100 micrograms/ml teniposide (0 +/- 0%), but not by amsacrine. These data indicate that prior exposure to etoposide and teniposide influence ara-C metabolism and possibly cytotoxicity, and thus should not immediately precede ara-C administration in clinical trials. PMID- 1602796 TI - Acute megakaryoblastic leukemia: establishment of a new cell line (MKPL-1) in vitro and in vivo. AB - A megakaryoblastic cell line (MKPL-1) was newly established from the bone marrow of an adult patient with acute megakaryoblastic leukemia. This cell line grew in single cell suspension with a doubling time of 30 h and consisted of large primitive blasts with persistent development of giant cells carrying multilobed nuclei. MKPL-1 cells were positive for platelet GPIIb/IIIa (CD41) and GPIIIa (CD61), and expressed OKM5 (CD36), MY7 (CD13), and MY9 (CD33) antigens in the absence of erythroid and lymphoid markers. The cytochemical and morphologic characteristics of MKPL-1 were also consistent with those of megakaryoblasts. The cells did not, however, express ultrastructural platelet peroxidase which is considered to be another marker of the megakaryocytic lineage. Cytogenetic analysis of MKPL-1 revealed a model chromosome number of 92 with abnormal chromosomes including those found in the patient's bone marrow cells. Furthermore, MKPL-1 cells were serially transplanted into nude mice for nine passages with production of lethal tumors and leukemic manifestation. Thus, our megakaryoblastic cell line which can be maintained both in vitro and in vivo would be useful for further studies of the biology of megakaryopoiesis and megakaryoblastic leukemia. PMID- 1602797 TI - Complete cytogenetic conversion in chronic myelocytic leukemia patients undergoing interferon alpha therapy: follow-up with reverse polymerase chain reaction. AB - Fifteen chronic myelocytic leukemia patients in durable complete cytogenetic conversion (CCC) under interferon therapy, were monitored every three to six months by bone marrow (BM) karyotypes and/or reverse-transcription polymerase chain reaction (RT-PCR) on peripheral blood (PB) leukocytes (by a nested primer approach using two rounds of amplification, 30 cycles each). Special care was taken to minimize the risk of contamination. The median time of follow-up after first CCC was 12 months (range, 6-30). Thirty five BM karyotypes were performed. Only three patients demonstrated the transient reappearance of a few Philadelphia positive metaphases, while other patients remained in CCC. Forty five PB samples were studied by RT-PCR. In two patients, no BCR/ABL transcript could be detected in three consecutive samples. In the 13 other cases, RT-PCR was intermittently negative, indicating a level of residual leukemic cells close to the threshold of sensitivity of the technique. PMID- 1602798 TI - Correlation of endogenous acetyl-ser-asp-lys-pro plasma levels in mice and the kinetics of pluripotent hemopoietic stem cells entry into the cycle after cytosine arabinoside treatment: fundamental and clinical aspects. AB - A decrease of endogenous acetyl-ser-asp-lys-pro (AcSDKP) levels in murine plasma was observed after Ara-C treatment. This decrease preceded the entry of pluripotent hemopoietic stem cells (CFU-S) into the cell cycle. This suggests a correlation between CFU-S kinetics and levels of endogenous AcSDKP. The subsequent increase of AcSDKP levels seem to indicate a feedback mechanism which should permit the reestablishment of homeostasis in the stem cells. Therefore, the expulsion of the physiological brake may be the response to a signal (stimulatory factors) to start dividing and the retention of the physiological brake may the mechanism for a return to normal values of cell proliferation. PMID- 1602799 TI - Interphase detection of trisomy 12 in B-cell chronic lymphocytic leukemia by fluorescence hybridization in situ. AB - Fluorescence hybridization in situ with a probe specific for the alphoid sequence of the centromeric region of chromosome 12 was used to evaluate seven cases of B cell chronic lymphocytic leukemia (B-CLL). Trisomy 12 was detected in interphase cells from one case which did not produce analyzable metaphases. Four out of the seven cases studied showed clear evidence of trisomy 12 in interphase nuclei. In situ hybridization provides an important supplement to classic cytogenetic studies of B-CLL and may help refine our understanding of the clinical correlations of chromosome abnormalities. PMID- 1602800 TI - Pulmonary leukostasis secondary to all-trans retinoic acid in the treatment of acute promyelocytic leukemia in first relapse. AB - All-trans retinoic acid has recently been shown to induce differentiation of acute promyelocytic leukemia cells in vitro and in vivo. Clinical trials of patients treated de novo, in first relapse, and with resistant disease have achieved a high rate of complete remission (CR). The overall toxicity is substantially less than standard induction chemotherapy, with the notable exception of deaths attributed to the development of pulmonary leukostasis coinciding with a rapid increase in the number of mature neutrophils. This report describes a patient who developed pulmonary leukostasis in the absence of significant leukocytosis. The patient survived pulmonary leukostasis, resumed therapy, and achieved a CR. The case demonstrates features of leukostasis which are peculiar to the 'retinoic acid syndrome'. PMID- 1602801 TI - Divergent patterns of leukemic cell growth in relation to normal hemopoietic precursors in long-term bone marrow culture. PMID- 1602802 TI - XVth Symposium of the International Association for Comparative Research on Leukemia and Related Diseases. Padova, Venice, Italy, October 6-11, 1992. PMID- 1602803 TI - A historical perspective of the International Association for Comparative Research on Leukemia and Related Diseases. PMID- 1602804 TI - HTLV-I infections in French Guiana as monitored by western-blot, dot-blot and PCR techniques. PMID- 1602805 TI - Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group. AB - Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers. PMID- 1602806 TI - Interleukin 2 (IL2) in the management of acute myeloid leukemia: clinical and biological findings. AB - In this paper we review some of the preclinical findings which have led us to believe that immunotherapy with interleukin 2 (IL2)/lymphokine activated killer (LAK) cells may be a feasible approach in the management of acute myeloid leukemia. The main clinical and biological results so far obtained with IL2 treatment, and the currently ongoing protocols and strategies are discussed. PMID- 1602807 TI - Multiphase process involved in radiation induced murine AML. AB - Exposure of 3 month old SJL/J mice to a single dose of 300 r yielded 15-30% acute myelomonocytic leukemia (AML) development at a mean latency of 1 year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence to 50%. All tumors were characterized by a partial deletion of one allele of chromosome 2 and the same deletion was detected in bone marrow and spleen cells of most irradiated mice, irrespective of the development of the disease. The presence of potential leukemic cells (PLC) in mice 4 months after the leukemogenic treatment was confirmed by transplantation studies. In these experiments PLC transition into overt AML seemed to be dependent on their transfer into irradiated recipients. Thus, exposure to 300 r results in the initiation of potential leukemic cells. Experiments were conducted in order to explore the possible role of radiation, cytokines and different hemopoietic growth factors on PLC promotion to overt leukemia. Exposure to 300 r, beside PLC initiation, was found to trigger the production of IL-6 and CSF-1; the additional administration of dexamethasone further increased CSF-1 levels. In vivo administration of CSF-1 into mice carrying radiation-induced PLC was most effective in PLC promotion to overt AML development. PMID- 1602808 TI - Mechanisms for the transformation of myeloid and erythroid cells by the nuclear oncogene V-myb. PMID- 1602809 TI - Detection of proviral DNA and viral RNA in various tissues early after avian leukosis virus infection. AB - Using molecular biological techniques, a study was made of the tissue tropism of avian leukosis virus (ALV) early after infection. Two strains of chickens, one with and the other without endogenous viral genes, were infected with ALV of subgroup A immediately after hatching; specimens of nine tissues and blood samples were analyzed at various times thereafter. A polymerase chain reaction (PCR), specific to ALV subgroup A, was used to detect proviral DNA and viral RNA. In situ hybridization was used to confirm the presence of proviral DNA in tissue samples and to calibrate the PCR. The pattern of detection of proviral DNA and of ALV-RNA in the various tissues was similar for both chicken strains. At 2 weeks of age, ALV-RNA was demonstrated in all tissues tested: bursa of Fabricius, thymus, bone marrow, proventriculus, liver, spleen, kidney, muscle, gonads, and blood samples, and at 4 weeks of age all tissues contained proviral DNA. No tropism for a specific tissue was observed early after an ALV infection. PMID- 1602810 TI - Essential thrombocythemia--clinical features, therapy and follow-up of 12 cases. AB - The authors analyzed twelve patients with symptomatic essential throthrombocythemia (E.T.) diagnosed from 1983 to 1991. Haemorrhagic and thrombotic phenomena were the main presenting features. Treatment consisted mostly of alpha-interferon (IFN-alpha 2b) subcutaneously in dosage ranging from 3 to 5 MU/m2 and hydroxyurea (HU) in conventional dosage. A clinical response was seen in seven patients treated with IFN-alpha 2b (4 CR and 2 PR), and in four patients treated with HU (3 CR and 1 PR). No significant side effects were observed. Our findings indicate that IFN-alpha 2b offers a non-leukaemogenic and very promising therapeutic alternative for E.T. PMID- 1602811 TI - Growth restraint and differentiation by LPS/TNF-alpha/IFN-gamma reorganization of the microtubule network in human leukemia cell lines. AB - The microtubule (MT) network of the cytoskeleton has been implicated as a mediator of cellular signal transduction; disorganization of this network may allow for mitogenesis. In previous work, loss of MT network organization in human MOLT4 and HUT78 T-cell leukemias was demonstrated in contrast to an organized "spoke-wheel-like arrangement" in normal human T-lymphocytes. In this study, loss of MT network organization was shown in several representative acute myeloid leukemia (AML) cell lines: KG1 myeloblastic, HL60 promyelocytic, and U937 myelomonocytic cells. Re-organization of the MT network was observed in HL60 and U937 AML cells treated with combined lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). This re-organization paralleled earlier work which showed this combination was effective in inducing monocytic pathway differentiation and growth restraint in HL60 cells, and growth restraint in U937 cells. In contrast, KG1 cells exhibited growth restraint, but did not re-organize with LPS/TNF-alpha/IFN-gamma treatment. These results are consistent with a role for the MT network in mitogenesis. Loss of MT network organization appeared to parallel the neoplastic phenotype in three AML cell lines, whereas MT network re-organization accompanied recovery of growth control in 2 of 3 AML cell lines. PMID- 1602812 TI - Cellular and molecular mechanisms in early hematopoietic differentiation. AB - Recently developed methodology allows virtually complete purification and abundant recovery of hematopoietic progenitors from human adult peripheral blood (PB) (1). We have recently utilized the population of stringently purified progenitors to investigate cellular and molecular mechanisms underlying the early steps of hematopoietic differentiation. Three aspects of these studies are briefly reported here. PMID- 1602813 TI - The current position of poikilotherms. AB - The major research themes in poikilotherm leukaemias, and their progress over the past two years are reviewed. Despite the fact that poikilotherms represent 99% of the animal world including man, background knowledge on most poikilotherm species is sparse. Furthermore, haemic systems in many poikilotherms have functions different to those of homeotherms. Most progress is being made in relation to lethal blood mutant neoplasms in Drosophila, leukaemias of farmed salmonids among the fishes, and among shellfish, the hemic sarcomas of bivalves. The hypothesis that epizootic neoplasia in fish and shellfish populations could be indicative of environmental pollution is being refined in the light of recent studies; environmental xenobiotics are no longer considered to play a primary aetiological role in either lymphomas and leukaemias of fish or haemic sarcomas of bivalves, although xenobiotics may have a primary role in other poikilotherm neoplasms. PMID- 1602814 TI - Application of a PCR-mismatch technique to the BCL-2 gene: detection of point mutations in BCL-2 genes of malignancies with A t(14,18). AB - The ability to conveniently detect single-base mutations in the DNA of clinical material without prior knowledge of the mutant sequence remains a diagnostic challenge. Most techniques suffer from a lack of general applicability to all DNA sequences, poor sensitivity, requirement for RNA samples rather than DNA, or necessity for performing DNA sequencing to uncover unknown point mutations. Recently, Montandon, et al. (8) described a novel method whereby segments of DNA amplified by the Polymerase Chain Reaction (PCR) can be rapidly screened for mutations through their formation of heteroduplexes with an end-labeled reference DNA followed by site-specific chemical cleavage at mispaired bases. Here we have applied this PCR-mismatch technique to a portion of the BCL-2 gene, using DNA samples derived from the biopsy specimens of patients with lymphomas or lymphocytic leukemias. The BCL-2 gene becomes activated through a t(14;18) chromosomal translocation in the majority of non-Hodgkin's lymphomas. Somatic point mutations were detected in the BCL-2 genes of 3 of 5 patient samples that contained a t(14;18). No mutations were observed for lymphomas lacking a t(14;18), nor in the DNA of over 20 normal persons. Further analysis excluded the possibility that the detected mutations represented hereditary polymorphisms or PCR-artifacts. Based on comparisons with direct DNA sequencing, the PCR-mismatch technique appeared to be both highly specific and sensitive. The possible mechanisms responsible for these somatic mutations in translocated BCL-2 genes and their functional significance are discussed. PMID- 1602815 TI - Murine leukemia virus induced central nervous system diseases. AB - The ts1 mutant of Moloney murine leukemia virus TB (MoMuLV-TB) causes a degenerative neurologic and immunologic disease in mice characterized by development of spongiform encephalomyelopathy that results in hind-limb paralysis, marked thymic atrophy associated with immunodeficiency, and generalized body wasting. T cells, particularly CD4+ helper T cells, play a key role in the pathogenesis of the disease induced by ts1. Therefore, ts1 is unique among the described murine retroviruses in its ability to afflict both the central nervous system (CNS) and the T-cell compartment of the immune system in the same host. This particular ability to cause degenerative diseases involving both the CNS and immune system is shared by the lentiviruses responsible for development of the acquired immunodeficiency syndromes of humans and macaques. Our goal has been to elucidate the specific cellular and molecular mechanisms that underlie this neuro- and immunopathogenicity of ts1. We have previously reported that the primary neuropathogenic determinant of ts1 maps to a single amino acid substitution, Val-25-Ile, in the precursor envelope protein gPr80env. Further, at the restrictive temperature, the Val-25-Ile substitution did not prevent oligomerization of the gPr80env proteins; however, the structure of the oligomer was incompetent for transport from the ER to the Golgi. These findings suggest that the cytopathic effect of ts1 in neural cells might be due to accumulation of the gPr80env oligomers in the ER. Since glial cells are targets of ts1 infection in vivo, primary astrocytic cultures were established and the cytopathic effect of ts1 and MoMuLV-TB on these cells assessed. Both viruses replicate well in astrocytes and their replication is cytopathic, albeit to different degrees. The ts1 mutant appears to produce greater cell killing than the wild-type virus. Furthermore, it was found that the rate of processing of gPr80env of ts1 in astrocytes is slower than that of MoMuLV-TB. Therefore, the inefficient transport and processing of gPr80env of ts1 appears to correlate with its cytopathic effect in these cells. Electron microscopic studies of the ts1 infected astrocytes revealed large numbers of aberrant particles in the ER. The in vitro cytopathic effect of ts1 on astrocytes may reflect what happens in vivo. An indirect mechanism of neuronal-cell killing by ts1 is proposed. PMID- 1602816 TI - The in vivo role of leukocyte function-associated antigen-1 in cytotoxic cell activity against tumors induced by Moloney-murine sarcoma/leukemia retroviral complex. AB - The in vivo role of LFA-1 molecule in the immune reaction to a murine retrovirus induced tumor was investigated. Local and systemic treatment with high doses of anti-LFA-1 monoclonal antibody led to tumor progression by blocking CTL interaction with tumor cells without interfering with CTL generation and localization in the tumor mass. PMID- 1602817 TI - Overproduction of metalloproteinases by v-mos-transformed rat kidney (6m2) cells. AB - Using monoclonal antibodies, we previously detected two forms of transformation associated proteins (TAPs), P64 and P68, in the rat kidney (6m2) cells transformed by the temperature-sensitive 110-murine sarcoma virus-Moloney-mutant. TAPs were secreted as glycoproteins by 6m2 cells grown at 33 degrees C, but not by 6m2 cells grown at 39 degrees C. The identity and functions of TAPs were previously unknown. By molecular cloning techniques and immunoscreening, we have isolated two different cDNA clones (34A and 79B3) that were found by Western blot analysis to code for an anti-TAP monoclonal antibody-reactive polypeptide of approximately 58,000 daltons. The nucleotide sequence of 34A cDNA was determined and found to be identical to that of rat transin-2. The deduced amino acid sequence of 34A shares 71% sequence identity with rat transin and 41% to 76% identity with three human metalloproteinases. Partial nucleotide sequencing data indicated that 79B3 may be the rat transin gene. When either 34A cDNA or 79B3 cDNA was used as a probe in Northern blot analysis, one mRNA band of approximately 1.9 kb was detected in 6m2 cells at the permissive temperature of 33 degrees C. Similar RNA was either not detected or detected at very low level in 6m2 cells grown at the non-permissive 39 degrees C. These results suggest that at the non-permissive 39 degrees C, these two genes were not transcribed at the same level as that at 33 degrees C. Zymogram further confirmed that P64 and P68 have metalloproteinase activities. Apparently, the two proteins which we formerly designated TAPs are members of the rat transin gene family. Therefore, within v mos transformed 6m2 cells, the absence of TAPs (metalloproteinases) at the non permissive temperature was due to the very poor transcription of the two rat transin genes. This article presents a review of the biochemical properties of TAPs and their eventual identification as rat transin-2 and transin. PMID- 1602818 TI - Gene therapy model for stromal precursor cells of hematopoietic microenvironment. AB - Marker bacterial Neor gene was transduced by retroviral gene transfer into stromal precursor cells making up the hematopoietic microenvironment in murine long-term bone marrow cultures (LTBMC). Cultures were infected six times during the first 3 weeks of cultivation. At 4 weeks, the adherent cell layers (ACLs) were implanted under the renal capsule of syngeneic unirradiated and irradiated mice. Cells from newly formed ectopic foci were explanted into secondary LTBMC. ACLs containing the marker gene were detected by polymerase chain reaction. About 74% of stromal cells in ACLs contained Neor gene. The possibility of stable gene transduction into stromal precursor cells competent to transfer the hematopoietic microenvironment was established. PMID- 1602819 TI - Structure, regulation and oncogenic mechanisms of HTLV-I and HTLV-II. PMID- 1602820 TI - The oncogenicity of Jun. AB - A mutational analysis of the delta region of the Jun protein shows an inverse correlation between transforming and transactivation potential of the mutant proteins if both properties are measured in chicken embryo fibroblasts. The possibility that Jun acquires oncogenicity not by gain but by loss of function is also suggested by the down regulation of the differentiation control element MyoD by Jun and by the low transactivating potential of highly transforming chimeric proteins of Jun and JunD and Jun and herpes simplex VP16. These observations raise questions concerning the relative importance of positive and negative transcriptional control signals imitated by Jun. PMID- 1602821 TI - Role of hemopoietic growth factors in the development and suppression of myeloid leukemia. AB - Myeloid leukemia development requires the acquisition by a cell of two abnormalities: an abnormal capacity for self-replication; and a capacity for autocrine stimulation, usually involving the known growth factors for granulocyte macrophage cells. Curiously, in human leukemia, this does not usually result in autonomous growth when assessed in clonal in vitro cultures. Depending on gene programming, in particular in human or murine myeloid leukemias, the hemopoietic growth factors can also suppress the leukemic population by inhibiting the capacity of the leukemic stem cells for self-generation. The regulator showing the highest suppressive activity varies from leukemia to leukemia, with G-CSF. GM CSF, IL-6, or leukemia-inhibitory factor (LIF) all having high activity on appropriate target cells. Combinations of these regulators are more effective than single agents alone. Analyses of human HL60, U937 and murine M1 leukemic models indicate that the development of morphological maturation in the leukemic cells is not a necessary feature of stem-cell suppression. LIF has an anomalous action on stem-cell self-generation, being highly effective in the suppression of certain myeloid leukemic cell lines, but being necessary to maintain self generation in normal embryonic cells. This suggests the existence of a common control medium governing self-generation decisions in cells of different lineages, but that the outcome of the decision is determined by the differentiation program operating in different cells. The colony-stimulating factors are being used in combination with chemotherapy in the treatment of patients with acute myeloid leukemia, but the above principles require caution in certain situations. PMID- 1602822 TI - Mitogenic activity of high molecular polysaccharide fractions isolated from the cuppressaceae Thuja occidentalis L. enhanced cytokine-production by thyapolysaccharide, g-fraction (TPSg). AB - Thuja polysaccharide g fraction (TPSg) was shown to be an inducer of the CD4+ fraction of the human peripheral blood T-cell subset (1,2). Furthermore, it could be demonstrated that TPSg is a potent inhibitor of the expression of HIV-1 specific antigens and of the HIV-1-specific reverse transcriptase (3). This report deals with the cytokine pattern induced by TPSg in human peripheral blood lymphocyte (PBL) and purified monocyte/macrophage cultures. In addition, a further characterization of the CD4+ T-cell fraction stimulated by TPSg was performed by FACS analysis. TPSg is induces IL-1 beta, IL-2, IL-3, IL-6, gamma IFN, G-CSF, GM-CSF, and TNF-beta production in PBL cultures; and IL-1 beta and IL 6 in monocyte/macrophage cultures. Enzyme-linked immunosorbent assays (ELISAs) demonstrated that no IL-4 was produced by PBL cultures under TPSg influence. PMID- 1602823 TI - Generation of nucleoside-resistant variants of HIV-1 by in vitro selection in the presence of AZT or DDI but no by combinations. AB - Several laboratories have shown that AZT-resistant variants of HIV-1 can be isolated from patients who have received prolonged therapy with this drug. Our laboratory has now been able to generate HIV-1 variants resistant to both AZT and ddI, in tissue culture, by using step-wise increases in the concentrations of each of these compounds over a 10-week period. This work has been performed by culturing wild-type clinical strains of HIV-1 as well as the HIV-3b laboratory strain of this virus under such conditions. The ID50 values obtained for the resistant viruses thus generated vary between 50-100 times above those of the parental wild-type strains in each case. Furthermore, we have identified several new mutation sites in the HIV-1 pol gene that are responsible for the observed resistance to AZT and ddI. We have not succeeded, however, in generating drug resistant strains of HIV-1, under conditions in which several compounds or anti viral agents were simultaneously present during the in vitro selection process. Combinations of drugs which failed to yield drug-resistant variants included AZT plus ddI, AZT plus alpha-interferon, and ddI plus alpha-interferon. These findings indicate that HIV drug resistance is less likely to occur in tissue culture when combinations of drugs are used, and provide rationale for the development of combination clinical trials for treatment of HIV-associated disease. PMID- 1602824 TI - Transfection of chronic lymphocytic leukemic cells with myc and ras. AB - Thirty samples of cells from twenty-one cases of chronic lymphocytic leukemia (CLL) were transfected with myc and/or ras. Transformation, as assessed by growth in liquid culture and change in morphology, occurred in only one case. Colony culture in semi-solid media, however, does not occur with these cells. It would appear that the neoplastic genotype of CLL cells does not predispose the cells to readily transform, even with transfection with these two oncogenes. PMID- 1602825 TI - Why are there so many leukemia viruses? PMID- 1602827 TI - Viral expressions in Reed-Sternberg cells. AB - In the murine system natural hybridoma formation was observed first in 1968-9. In the #620 to 818 system a mouse leukemia virus-(MLV-) producer diploid lymphoma cell fused with an immune plasma cell. The tetraploid fusion product cells grew in suspension cultures and as ascites tumors in mice and continued the production of MLV particles and MLV-neutralizing antibodies. Analogy between the #620 to 818 system and the origin of RS cells is proposed. Indirect evidence suggests retroviral infection of the mononuclear HD cell which presumably is an interdigitating reticulum (IR) cell. Reactive B and T cells interact in an abnormal manner and fuse with the retrovirally infected IR cell. The fusion product cells display hyperdiploidy and a disarray of markers as IR markers are lost due to dedifferentiation (and regained upon differentiation induction) and B and/or T cell markers are gained. Conventional theories for the origin of RS cells fail to explain the great heterogeneity of their markers. Derivation of RS cells from IR cells and B and/or T lymphocytes as natural hybridomas offers plausible explanation for all the features of RS cells. PMID- 1602826 TI - Differentiation and activation antigens on blood mononuclear cells in lymphocytic leukemia before and during IFN-alpha 2B therapy. AB - Expression of differentiation and activation antigens on peripheral blood mononuclear cells of four chronic lymphocytic leukaemia (CLL) patients was studied before and during interferon-alpha 2b therapy. Patients had clinical stage B(II) disease, a lymphocyte count of over 60 G/l and a lymphocyte doubling time shorter than 12 months. One of the patients unresponsive to previous chemotherapy experienced a substantial decrease of the lymphocyte count during interferon-alpha 2b (IFN-alpha 2b) therapy, with a nadir at one fifth of the initial value while on this therapy. The lymphocyte count decreased slightly in a further patient, while it increased in two patients. Treatment with IFN-alpha 2b left the phenotype of CLL lymphocytes essentially unchanged. The elevated serum beta-2 microglobulin values increased further during treatment with the exception of the CLL patient responsive to IFN-alpha 2b therapy. The clinical stage of the disease did not change in any of the patients when evaluated according to the criteria of the International Workshop on CLL. Further studies are necessary to determine which of the CLL patients benefit from therapy with interferon-alpha 2b. PMID- 1602828 TI - Human T-cell leukemia virus type I as agent inducing genetic changes in infected human lymphocytes. AB - Sera and DNA samples, including cord blood, were examined from six members of a three-generation family suspected of being carriers of HTLV-I. Serum antibodies to HTLV-I were detected by Western blot analysis more clearly in adults than in children. DNA sequences related to HTLV-I-gag and -tax, but not -pol genes were detected more clearly in specific PCR products of DNA of adults than those of children, and of the cord blood by Southern hybridization analysis. HTLV-I related DNA sequences were also detected in some HTLV-I-seropositive as well as seronegative patients with T-cell dyscrasia and with other diseases, including carcinoma. Frequencies of chromosome abnormalities were found to be significantly higher in lymphocytes of HTLV-I-seropositive persons than in those of HTLV-I seronegative persons. Immortalization of cultured lymphocytes following infection with HTLV-I was found to be accompanied by chromosome and gene rearrangements. Transformation of these cells following treatment with carcinogens was found to be accompanied by additional chromosome rearrangements. These results suggest that some persons may be born with HTLV-I-related sequences that are repressed in childhood. Repeated expression of their products may result not only in the host antibody response but also in increased chromosomal instability and in increased risk for further genetic changes of carrier cells when exposed to environmental carcinogens. PMID- 1602829 TI - Studies on the mechanisms of HTLV-I leukemogenesis. AB - The factors that regulate low viral expression and long latency after HTLV-I infection are poorly understood. To study the possible mechanisms involved in the regulation of gene expression and cell transformation, we studied whether (1) methylation could play a role in viral transcription, and (2) tax product could favor chromosomal instability. The results indicate that methylation of HTLV-I LTRs blocks their transcriptional activity and that tax protein triggers DNA damage. PMID- 1602830 TI - cDNA sequencing confirms HTLV-I expression in adult T-cell leukemia/lymphoma and different sequence variations in vivo and in vitro. AB - Human T-lymphotropic virus type I (HTLV-I) is the etiological agent of adult T cell leukemia/lymphoma (ATL) and of tropical spastic paraparesis/HTLV-I associated myelopathy (TSP/HAM). In both diseases, expression of viral message can generally only be demonstrated by the reverse transcriptase-polymerase chain reaction (RT-PCR) technique. We have previously reported on the the expression of at least four types of alternatively spliced pX mRNAs in vitro and in vivo (1). The sequence variation between HTLV-I pX cDNAs cloned from two different HTLV-I infected cell lines and from uncultured primary peripheral blood mononuclear cells (PBMC) from two ATL patients was examined. None of the cDNA clones from one of the ATL samples was completely identical to any of the previously cloned cell line messages, establishing that the demonstration of HTLV-I mRNA in ATL is not the result of PCR contamination. Sequence analysis showed that differences between samples can be clustered according to their geographic origin. Cell line cDNAs showed a more marked sequence drift than ATL cDNAs, especially in the long terminal repeat (LTR), demonstrating association of intrastrain variability with culture in vitro. Intrastrain cDNA variability in vivo also suggests ongoing viral replication in infected individuals. A premature stop codon in the pX-II open reading frame (orf) was a common finding, suggesting that the complete putative pX-II protein is not essential for T-cell immortalization or HTLV-I replication. PMID- 1602831 TI - Expression and biological significance of human endogenous retroviral sequences. AB - The human genome contains a variety of elements resembling mammalian retroviruses. Most of these sequences have been found to be related to primate and murine C-type viruses (BaEV, SSAV/GaLV, MuLV), murine B-type viruses and A type particles (MMTV, IAP), or human T-cell lymphotropic viruses (HTLV). Altogether, human endogenous retroviruses and retroviral elements are estimated to comprise at least 0.1 to 0.6% of the human genome. Like other transposable elements they may contribute in shaping the eukaryotic genome by intracellular transposition events or by generating hot spots of recombination. Human retroviral sequences have been shown to be transcriptionally active, especially in human placenta and embryonic tissue and in human tumor cell lines. Some elements that are coexpressed with cellular sequences are supposed to play a role in regulation of gene expression. Furthermore, expression of human endogenous retroviral sequences may have a protective function against superinfection by related exogenous retroviruses. On the other hand, endogenous retroviruses and retroviral elements represent a cellular reservoir of possibly pathogenic retroviral genes. They may be involved in chromosomal aberrations by acting as sites for recombination events between different chromosomes. Furthermore, they can act as insertion mutagens and activate or inactivate cellular genes. Retroviral gene products themselves may also be pathogenic as has been shown for the immunosuppressive effects of p15E envelope proteins. Therefore, the role of human endogenous retroviruses and retroviral sequences in biological processes is currently a subject of great interest. PMID- 1602832 TI - Virulence in lymphomagenesis is modulated by alterations in proteins binding to CORE and GRE-LVa elements of the MoMuLV enhancer. AB - Changing nucleotide 3 of the CORE consensus from T to C has no effect on the binding of a 42 kDa protein, which has little affinity for the CCAAT binding site. Changing nucleotide 6 of the CORE consensus from T to C significantly reduces binding of the 42 kDa protein. Studies on the pathology induced by various MoMuLV mutants with CORE mutations showed that the CORE elements are important in modulating virulence in T-cell lymphomagenesis in BALB/c mice. However, disease specificity appears to be influenced as much by the host as it is by the virus. LVa is preferentially bound to the GRE-LVa sites. Deletion of nucleotide 9 and changing nucleotides 10 and 11 from GG to AA in the GRE-LVa element does not disrupt binding of LVa. Changing nucleotide 10 from G to A and nucleotide 13 from A to T in the GRE-LVa element does not disrupt binding of GR but allows binding of a novel protein which displaces or abolishes binding of LVa. These five nucleotide changes alone do not alter disease specificity and had a minimal effect on virulence in T-cell lymphomagenesis in BALB/c mice. Additionally, changing nucleotide 3 in CORE(a) and nucleotide 6 in CORE(b) does not alter disease specificity but has a small additional effect on virulence in T cell lymphomagenesis. PMID- 1602833 TI - TNF-alpha and radiation-induced thymic lymphomas. PMID- 1602834 TI - Role of the p53 tumor suppressor gene in the pathogenesis and in the suppression of acute lymphoblastic T-cell leukemia. AB - The tumor suppressor gene p53 has been shown to be mutated in 50% of acute lymphoblastic T-cell-leukemia (T-ALL) cell lines, all of which were established from T-ALL cases in relapse. In these lines both alleles of the p53 gene were independently affected by point mutation. In contrast, in human solid tumors possessing a mutated p53 allele, the second wild-type p53 suppressor allele is often lost by deletion rather than altered by mutation. This suggests that in T ALL cell lines, the product encoded by the second mutated allele provides the cells with an additional oncogenic stimulus, beyond the loss of suppressive activity. While different p53 mutations have been shown to possess differential oncogenic potential in the p53 plus ras cotransformation assay, in T-ALL cells different mutations may in addition possess distinct functions, further contributing to the tumorigenic phenotype. PMID- 1602835 TI - Interaction of large granular lymphocytes with susceptible target does not induce second messenger and cytolytic granule exocytosis. AB - We studied the activation signals of LGL, from LDGL patients, following incubation with susceptible K562 target cells. The findings showed that LGL lysis is independent of [Ca2+]i rise and cytolytic granule exocytosis, and most likely involves alternative, as yet unidentified, mechanisms. PMID- 1602836 TI - Regulation of SRC-family protein tyrosine kinases by interleukins, IL-2, and IL 3. AB - Unlike many other growth factor receptors, the known subunits of the receptors for the Interleukins IL-2 and IL-3 lack intrinsic tyrosine kinase activity, and yet increases in the phosphorylation of proteins on tyrosines is a rapid event in hematolymphoid cells following stimulation with these lymphokines. Here we show that IL-2 and IL-3 regulate the activity of specific members of the SRC-family of non-receptor protein tyrosine kinases (PTKs). In IL-2-dependent T-cell lines, IL 2 induced rapid and transient increases in the activity of the p56-LCK kinase without influencing the activities of other SRC-like PTKs (p59-FYN, p62-YES) in these T-lymphocytes. In contrast to IL-2's effects on p56-LCK in T-cells, studies of an IL-2-responsive cell line of the B-cell lineage that lacks p56-LCK revealed that IL-2 specifically regulates the activity of the p53/56-LYN kinase. Thus, some flexibility exists in the ability of various SRC-like PTKs to functionally couple to IL-2 signalling pathways. In several IL-3-dependent myeloid-committed leukemic cell lines, IL-3 was found to specifically regulate the activity of the p53/56-LYN kinase without affecting the activities of other SRC-like PTKs (p59/64 HCK, p59-FYN, p62-YES) in these hematopoietic cells. This finding that p53/56-LYN can be regulated by both IL-2 in B-lineage cells and IL-3 in myeloid-committed cells demonstrates that the same SRC-family PTK can participate in signal transduction events mediated via two independent receptor systems. Taken together, our findings imply that the specific combinations of lymphokine receptors and SRC-like PTKs available for coupling with those receptors are coordinately controlled during the differentiation of hematopoietic cells. PMID- 1602837 TI - Cytosolic free calcium in lymphoblasts from young, aged and Alzheimer subjects. AB - Altered cellular calcium homeostasis may be important in the pathophysiology of aging and Alzheimer's disease. Calcium transport by freshly isolated lymphocytes declines with Alzheimer's disease compared with age-matched controls. To determine if these changes occur in the absence of complications due to drugs, diet or any of the other variables that are dependent upon the state of the patients, cytosolic free calcium ([Ca2+]i) was determined in cultured lymphoblasts from young and aged control subjects, as well as from Alzheimer patients. Lymphoblast [Ca2+]i was determined with the fluorescent probe fura-2 in either the presence or absence of serum. In cells that were grown in serum free medium, neither growth rates nor [Ca2+]i varied between groups. Growing cells in serum containing medium doubled growth rates and [Ca2+]i. However, [Ca2+]i from young, aged and Alzheimer groups were still similar. Thus, an age- or Alzheimer related alteration in [Ca2+]i does not occur in cultured lymphoblasts. PMID- 1602838 TI - Insulin resistance in Werner's syndrome. AB - Insulin resistance in Werner's syndrome (WS) was studied using the glucose clamp technique, and compared with physiologically aged and young subjects. Fasting immuno-reactive insulin (IRI) was increased in patients with Werner's syndrome compared with aged and young subjects. Metabolic clearance rate (MCR) of glucose was decreased in the aged and WS. A rightward shift of the dose-response curves of insulin and MCR of glucose was observed in the aged and WS with a more pronounced shift in the latter. MCR of insulin was also decreased in WS. [125I]insulin binding to erythrocytes was similar in the three groups. These results suggest that insulin resistance associated with WS is due to a post binding defect manifested by a rightward shift of the dose-response curve of insulin-induced glucose disposal and a decrease in insulin clearance rate. PMID- 1602839 TI - Modulation of age-related alterations in membrane composition and receptor associated immune functions by food restriction in Fischer 344 rats. AB - Food restriction is known to modulate aging and age-associated immune functions in rodents. In an attempt to understand the mechanism(s) through which food restriction delays age-associated loss of certain immune functions, lipid composition of spleen cells as well as binding of spleen cells to interleukin-2 (IL-2) and insulin were analyzed in four month-old and 19-month-old ad libitum fed (AL) and food-restricted (FR) Fischer-344 male rats. The results revealed that although AL-fed rats did not show a difference in age-related changes for IL 2 and insulin binding, the number of binding sites were significantly increased in the spleen cells of 19-month-old FR animals when compared with those of the 19 month-old AL group. When spleen cell phospholipid fractions were analyzed for fatty acid composition, the spleen cells from FR animals consistently revealed higher linoleic acid (18:2) levels and significantly lower arachidonic acid (20:4) and long chain fatty acid, docosatetraenoic acid (22:4) levels in the phosphatidylcholine and phosphatidylethanolamine fractions than the spleen cells of the AL rats. Further, spleen cell plasma membranes of FR rats also exhibited similar changes showing higher 18:2 and lower 20:4 and 22:4 levels than the AL animals. Finally, spleen cells obtained from 19-month-old FR animals produced higher levels of IL-2 and lesser prostaglandin E2 when compared to 19-month-old AL animals. The above observations suggest that one of the mechanisms through which food restriction may delay the loss of age-associated immune functions is through modulation of the fatty acyl composition of phospholipid fractions of spleen cell membranes. This modification may facilitate binding of IL-2 and insulin to their receptors and thus may improve T cell proliferation and prevent or delay age-related loss in immune functions. PMID- 1602840 TI - Effects of ageing and exercise on soleus and extensor digitorum longus muscles of female rats. AB - The effects of ageing and of exercise on muscle mass, fiber cross-sectional area, and fiber type composition of a weight-bearing muscle, the soleus and a non weight-bearing muscle, the extensor digitorum longus (EDL) were investigated in female Long-Evans rats. The animals were exercised by means of voluntary wheel running beginning at 4 months. Runners and sedentary controls were studied at 9 months and 27 months of age. In sedentary rats, the soleus muscle weighed 26% less, and the EDL weighed 19% less at age 27 months, than at 9 months. This decline in muscle mass was accounted for by a similar decrease in muscle fiber cross-sectional area. The wheel running resulted in significant hypertrophy of the soleus in both 9- and 27-month-old rats; as a consequence the 27-month-old runners had larger soleus muscles than the 9-month-old sedentary rats. The running did not prevent atrophy of the EDL in the old rats, but did increase the proportion of type IIa fibers. The exercise also increased the number of capillaries per fiber in the soleus muscles of both young and old rats. In conclusion, the finding that wheel running prevented atrophy with ageing of the weight-bearing soleus but not of the non-weight-bearing EDL emphasizes the specificity of exercise, and shows that exercise-induced muscle hypertrophy can be maintained in old age by appropriate exercise. PMID- 1602841 TI - Decrease of phosphorylating oxidation and increase of heat producing NADH oxidation in rat liver mitochondria during life-span prolongation of rats by calorie-restricted diet. AB - The influence of calorie-restricted diet, initiated at weaning, on some of the oxidative processes in liver homogenates and isolated mitochondria of 2-, 3-, 4-, 24-, 35- and 45-month-old male Wistar rats was studied in comparison with control ad libitum-fed 1-2 day-old rats and 0.5-, 1-, 2-, 3-, 4- and 24-month-old rats. It was shown that a calorie-restricted diet (at 37% of the ad libitum calorific level) did not change the rate of succinate oxidation coupled with oxidative phosphorylation in homogenates, but resulted in a decrease of succinate, glutamate plus malate and beta-hydroxybutyrate oxidation and cytochrome c-oxidase activity in isolated mitochondria without any uncoupling of oxidative phosphorylation or change in cytochrome content in the mitochondria. On the other hand, a significant increase in mitochondrial rotenone-insensitive NADH oxidation and a higher liver mass/body mass ratio in rats under the calorie-restricted diet was established. It may be considered that the activation of a heat-producing mechanism is a very important physiological function in such a condition. PMID- 1602842 TI - Longitudinal Gompertzian analysis of cervical cancer mortality in the US, 1962 1987: a method of quantitatively demonstrating changing environmental influences upon deterministic mortality dynamics. AB - Age-specific mortality rates for cervical cancer (CC) in the United States from 1962 through 1987 were subjected to longitudinal Gompertzian analysis. Age specific CC mortality rate distributions for women display two distinct Gompertzian slopes, one between age 20 and 35 years and the other between age 40 and 85 years. These two distinct Gompertzian regions suggest that CC may be clinically and biologically classified into pre- and postmenopausal varieties, similar to breast cancer. Between 1962 and 1987, the annual crude CC mortality rate declined 60.0%. The basis for the decline of CC mortality is shown to be that aggregate environmental (etiopathogenic) influences upon premenopausal CC age-specific mortality rate distributions decreased 57.8%, and upon postmenopausal CC, decreased 28.0%. PMID- 1602844 TI - (-)deprenyl and (-)parafluorodeprenyl-treatment prevents age-related pigment changes in the substantia nigra. A TV-image analysis of neuromelanin. AB - With the aid of TV-image analysis the number, the area and the density features of melanin granules in neurocytes of the substantia nigra in a group of 3-month old naive male rats and in a 21-month-old group of male rats treated for 18 months with saline, (-)deprenyl and (-)parafluorodeprenyl, respectively, were determined. According to the Kolmogorov 2-sample test the two drug-treated groups do not differ significantly from each other in the number, total area and area of one pigment granule. In the aged saline-treated group the number of melanin granules decreased significantly and the area of the melanin granules increased in comparison to young controls as well as to the drug-treated groups. PMID- 1602843 TI - Effect of neurotensin on contractile activity and [3H]acetylcholine release in cat terminal ileum during different postnatal periods. AB - The effect of neurotensin (NT) on the contractile activity of circular and longitudinal strips from the terminal ileum of 15-, 30-, 60-day-old and adult cats as well as on the resting and electrically-evoked release of [3H]acetylcholine (ACh) was studied. Radioactivity was measured by liquid scintillation spectrometry and the effect of NT was evaluated by the S2/S1 ratio. In the circular muscle strips NT (1-100 nM) inhibited spontaneous contractions in all age groups. In the longitudinal strips the effect of NT was concentration- and age-dependent. NT at a concentration of 1 nM had no effect on the spontaneous activity in 15-day-old cats, but in the other age groups in 70-80% of the cats it inhibited spontaneous contractions. The response to 10 and 100 nM NT was either biphasic (relaxation followed by contraction) or inhibitory: in 15-day-old cats the response was biphasic only and with increasing age the percentage of strips responding with inhibition of the contractions increased. Neither substances affecting adrenergic and cholinergic transmission nor TTX changed the inhibitory response to NT. The contractile component of the biphasic response was TTX resistant in all age groups and was significantly decreased by scopolamine in 60 day-old and adult cats. NT increased both resting and electrically-evoked release of [3H]ACh which was not changed by TTX. In the presence of the peptide the S2/S1 ratio increased as NT-induced [3H]ACh release in the strips of adult cats was higher than that in young cats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602845 TI - Enhanced unscheduled DNA synthesis by secondary cultures of lung cells established from calorically restricted aged rats. AB - Unscheduled DNA synthesis (UDS) induced by two exposure levels of ultraviolet light (UV) or two concentrations of methyl methane sulfonate (MMS) was evaluated in secondary cultures of lung fibroblasts established from weanling, 11-month-old and 31-month-old female Fischer 344 rats fed ad libitum (AL) or calorically restricted (CR) diets. [3H]Thymidine incorporation as a function of UDS was highest for weanling-derived cells treated with either UV or MMS, declining consistently with increased age between cells from weanling, 11-month-old and 31 month-old animals. [3H]Thymidine incorporation as a function of UDS in cells from 11-month-old AL vs. CR rats differed only at the highest UV exposure level. In contrast, cells derived from 31-month-old CR rats exhibited UDS levels which were at least twice as high at each UV treatment level as UDS levels of cells derived from the same age AL rats. Cells from both old AL and old CR rats were shown to initiate DNA excision repair at about the same rate. Cells from CR rats, however, repaired DNA damage at an accelerated rate and completed excision repair while repair in cells from AL animals was slower and apparently did not proceed to completion. Data from this study indicate that cells from young and old AL and CR animals initiate excision repair, but demonstrate an age-related loss of UV- or MMS-stimulated [3H]thymidine incorporation in cells derived from AL animals. Cells derived from CR animals did not exhibit that age-related loss of UDS activity; rather, they showed an enhanced UDS response to DNA damage and appeared to complete ligation as the final step in excision repair. The data suggest that caloric restriction of a cell donor animal not only delays the age-associated decrease in in vitro DNA excision repair capacity in cells from that animal, but may actually enhance repair capacity. PMID- 1602847 TI - Immune control of mammalian aging: a T-cell model. AB - A competent immune response appears to play an important role in retarding aging. On the other hand, the aged immune system is assumed to accelerate the general aging process. In order to approach the underlying mechanism of this paradoxical immune response, the process of clonal deletion in the thymus is addressed under the aspect of aging. It is assumed that T-cell deletion in the thymus brings about a control of cell differentiation in the organism. For proper functioning, this control is suggested to be directed, in the sense of a feedback mechanism, primarily to thymic stromal cells involved in the process of clonal deletion. At the expense of a thymus atrophy, the control system can retard aging up into the reproductive period of life. With the progress of thymic involution, however, the control is predetermined to undergo a breakdown and, in consequence, through loss of self-tolerance it speeds up the whole aging process. PMID- 1602846 TI - Histochemical characterization of the aging microvasculature in the human and other mammalian and non-mammalian vertebrates by the periodic acid-Schiff reaction. AB - Prior histochemical studies with the periodic acid-Schiff (PAS) reaction have shown altered biochemical composition in a limited part of the microvasculature (MV) in aging in two species of laboratory animals. We therefore studied, with the PAS reaction, all the components of the MV in multiple tissues from various immature, adult and aged mammals, including human, and immature and aged nonmammalian vertebrates. We now demonstrate that there is an altered biochemical composition of capillaries, arterioles and venules in various tissues with aging. These are first detectable somewhat beyond half the life-span in man (greater than 45 years), marmoset (5 years) and dog (8 years) and seen in old fish, reptiles and birds. The capillary wall is increasingly PAS+; in arterioles there are focal PAS+ areas in the media which increase in size and number with age and become hyalinized masses. The non-muscular venules are increasingly PAS+ apparently due to a polysaccharide staining of connective tissue elements. These histochemical changes in the MV with aging are in the extracellular matrix and appear to be a specific manifestation of aging in vertebrates. The consequences of such changes in MV aging may be important physiologically. PMID- 1602848 TI - A procedure for measuring neuromelanin in neurocytes by a TV-image analyser. AB - With the aid of a Robotron A6471 type TV-image analyser the number, total area, area of one granule and density features (sum, average of gray values and average gray value of one pigment granule) of melanin granules in neurocytes of the substantia nigra in 3-month-old and 3-year-old male rats were determined. The number of cells in sections of identical areas was similar in the young and old rats. A statistically non-significant difference between the two age cohorts in the proportion of neurocytes with and without melanin was found; 773 (48.1%) and 853 (51.8%), in the young rats and 1219 (65.1%) and 652 (34.8%) in the old ones. Within the melanin containing neurocytes, however, statistically conspicuous, age related differences in the number, area and density features of melanin granules were discovered. The majority of the neurocytes in young rats contained numerous, small sized neuromelanin granules, whereas in the majority of the neurocytes of old rats smaller numbers of large sized, neuromelanin granules were detected. PMID- 1602849 TI - [Infective endocarditis in heroin addicts in the province of Cadiz. A multicenter study of 150 cases]. AB - BACKGROUND: Given the progressive increase in infectious endocarditis (IE) in intravenous drug addicts (IVDA) in the province of Cadiz the present study was designed with the aim of studying the epidemiologic and clinical characteristics of this disease in our environment. METHODS: One hundred fifty episodes of IE occurring in 133 IVDA admitted to 6 hospitals in the province of Cadiz were studied in an open, multicentric study with a protocol of gathering of common data. Well known diagnostic criteria were used for this process and a univariant technique was employed in the analysis of prognostic factors. RESULTS: Fifty three percent of the episodes occurred in the county of Campo de Gibraltar and 32% in the area of the Bay of Cadiz. The increase of the disease has been progressive since 1984 and marked over the last two years. All the patients presented fever, abnormal chest radiography in 90% and the process was produced by Staphylococcus aureus in 88%. Echography was abnormal in 85% of the episodes and vegetation was identified in 75%. The IE was located as right in 90%, mixed in 5% and left in 5%. Surgical treatment was required in 4 patients. Mortality was of 9%. Mixed or left location (p = 0.00003) and the development of the respiratory distress syndrome of the adult (p = 0.00001) were significantly associated with greater mortality. CONCLUSIONS: Infectious endocarditis in intravenous drug addicts maintains a well defined pattern of clinical expressivity and presents identifiable factors of prognostic influence. The increase in its prevalence in the province of Cadiz is probably due to a parallel increase in the addiction to intravenous heroin in this area. PMID- 1602850 TI - [Septic arthritis induced by pyogenic germs in patients without parenteral drug addiction. Analysis of 44 cases]. AB - BACKGROUND: The aim of this study was to evaluate the clinical-microbiological characteristics presented in the area of influence of the Hospital de Bellvitge Princeps d'Espanya, of articular infection induced by pyogenic germs in patients without intravenous drug addiction. METHODS: All the cases of microbiologically confirmed articular infection in patients without intravenous drug addiction diagnosed during the period of 1981-1990 were evaluated by protocol. RESULTS: Five cases (11%) with gonococcal arthritis and 39 cases (89%) of non gonococcal arthritis were observed with Staphylococcus aureus being the causal germ in 27 cases. Sixty percent of the patients presented one or more predisposing factors for the appearance of infectious arthritis. Monoarticular involvement was seen in 84% of the cases. At the time of diagnosis fourteen patients presented radiological signs compatible with septic involvement, with the isotopic study with 99mTc being positive in the 27 cases in which it was carried out. Delay in diagnosis was of 20 +/- 25 days. Functional results were considered as satisfactory in 57% of the cases. CONCLUSION: In the area of influence of the Hospital de Bellvitge-Princeps d'Espanya, the prevalence of gonococcal arthritis is low. Gram positive germ are the most frequent causal agents in all the age groups studied. Gammagraphy with 99mTc presented high profitability in the diagnosis of articular infections. The functional results observed were not optimal and improvement of the same probably requires a shortening in the time of delay in diagnosis. PMID- 1602851 TI - [Logistic model for predicting the prognosis in patients with intra-abdominal infection based on the APACHE II index]. AB - BACKGROUND: The APACHE II method has been widely used to classify patients according to disease severity. The high mortality and the lack of reliable prognostic parameters justify the study and application of indexes of severity (IS) and prognostic indexes (PI) in patients with intraabdominal sepsis. METHODS: A prospective study is presented concerning 100 patients with intraabdominal sepsis in whom a prognostic index derived from the APACHE II method by means of a logistic regression model was applied. In this model the APACHE II score is used as the only independent variable with the aim of predicting the outcome (mortality or survival) at the time of hospital admission. RESULTS: The predictive values obtained, with a 70% probability of mortality taken as the cut off point, were: sensitivity 100%, specificity 87.7% and total predictive capacity 91%. CONCLUSIONS: It was concluded that the logistic prediction model of prognosis shows a high correlation with patient outcome and the application of the APACHE II score is useful in patients with intraabdominal infection. PMID- 1602852 TI - [Cholera again]. PMID- 1602853 TI - [Heroin and infection]. PMID- 1602854 TI - [Lymphomatoid granulomatosis: clinicopathologic analysis of 7 cases]. AB - The aim of the present was to study the possible clinical histological correlations in the cases of lymphomatoid granulomatosis (LG) diagnosed in the last 10 years. Clinic evolutive data were collected in 7 patients diagnosed LG. The histological samples related to the same were revised and an immunohistochemical study was carried out with the oxidase/antiperoxidase technique. Seven patients (5 females and 2 men) with a mean age of 47 years (limit 23-47) were studied. The form of presentation was alteration of the general state in 5 cases accompanied by respiratory symptoms in 4. In 2 cases lung involvement was not found. In 7 biopsies performed at the initiation of the disease, 3 presented characteristics of lymphoma. Three patients are presently alive with a mean follow up time of 31 months and 4 have died (mean survival 17 months). Immunohistochemistry demonstrated T lymphocyte predominance in most of the cases (5 out of 6). The first case of LG in a patient simultaneously infected with the HIV and HTLV-1 is presented. Lymphomatoid granulomatosis possesses a symptomatology which is very inspecific and has histological features which may be superposed to other lymphoproliferative disorders, specially those of the T strain. Given the known relation between HTLV-1 and T lymphomas the role of HTLV 1 in the genesis of LG should be studied in these patients specially in those with the HIV. PMID- 1602856 TI - [Attitudes towards active euthanasia and its legislation in Spain]. AB - BACKGROUND: The present forms of carrying out public health care have lead to probably more effective medicine but which at the same time has led to greater risks in violating patients' rights and welfare. At present, a series of arguments are been debated for soliciting the legalization of euthanasia as a form of avoiding possible abuses. Thus, the opinions and attitudes concerning legislation for active euthanasia in terminally ill patients were herein investigated. METHODS: An anonymous survey was elaborated in which 1,109 subjects from three sectors of the population participated: a) hospital personnel (doctors n = 346 and nurses n = 346) of the University Hospital San Carlos in Madrid, b) students (n = 261) of the University Complutense of Madrid, and c) retired people (n = 156) in an old age residence in the province of Madrid (Pinto). The sample was made up of a total of 446 males and 657 females with ages of between 20 and 90 years. RESULTS: Most of those surveyed were in agreement in determined circumstances or totally in agreement with legislation for active euthanasia in terminally ill patients (63%). With respect to acceptation to the practice of legislation for active euthanasia 63% were in agreement in determined circumstances or totally in agreement. Significant differences were found (p less than 0.05) in relation to age, sex, marital status, religion and political ideology of the subjects. CONCLUSIONS: Although the results found in this study concerning the opinions and attitudes on legislation for active euthanasia in terminally ill patients coincided when compared with other existing studies with respect to acceptation for legislation, a less favorable tendency to the same was evident. PMID- 1602855 TI - [Tuberculous meningitis with atypical presentation in a patient with human immunodeficiency virus infection]. AB - A 32 years old male patient is described with infection by the human immunodeficiency virus (HIV) on stage IV C1 and with positive Ag p24 who developed tuberculous meningitis of atypical presentation. A persistent liquoral neutrophilia and low adenosindeaminase values were observed in cerebrospinal fluid of purulent appearance. The patient responded badly to tuberculostatic treatment and died. In the antibiogram carried out resistance to Mycobacterium tuberculosis was observed to rifampicine and isoniazide, two of the five drugs the patient had received. The peculiarities of the clinical form of presentation similar to purulent bacterian meningitis are discussed, and the possible influence of HIV infection and the antibiotic multiresistance observed in the bad evolution of the tuberculous meningitis which the patient developed. PMID- 1602857 TI - [Dysfunction of the Oddi's sphincter]. PMID- 1602858 TI - [Quo vadis, public health?]. PMID- 1602859 TI - [Colitis and Hafnia alvei]. PMID- 1602860 TI - [Schwannomatosis, an entity different from neurofibromatosis?]. PMID- 1602861 TI - [Arterial aneurysm and myositis secondary to Salmonella typhimurium bacteremia in patient with human immunodeficiency virus infection]. PMID- 1602862 TI - [A case of acute amitriptyline poisoning]. PMID- 1602863 TI - [Inefficacy of hemoperfusion in acute poisoning with tricyclic antidepressives]. PMID- 1602864 TI - [Syncope as presentation form of pulmonary thromboembolism. Study of 15 cases]. AB - BACKGROUND: To evaluate the prevalence of syncope as a form of presentation of pulmonary thromboembolism (PTE) in the emergency department of a general hospital. METHODS: All the cases of PTE having gone to the emergency department between May 1983 and July 1989 were collected. A radiography of the thorax, arterial gasometry, an electrocardiogram and a pulmonary perfusion scintigraphy were performed in each patient. Ventilation scintigraphy and/or pulmonary DIVAS were also carried out when necessary. RESULTS: Of a total of 63 patients, 15 (24%) had a syncope as a primary manifestation. No significant differences were observed in regards to predisposing factors between the syncope group (S) and the non-syncope group (NS) with there being a predominance of women in the S group (p less than 0.05). Furthermore, the S group had a greater prevalence of tachycardia, hypotension, electrocardiographic changes, pleural effusion and perfusion defect greater than 50% in the pulmonary scintigraphy. CONCLUSIONS: PTE should be discarded in any patient with a clinical picture of syncope with hypotension and tachycardia, especially if female. When PTE is presented as a syncope it is generally a massive embolism. PMID- 1602865 TI - [Main errors in the discharge report and in the registry book of a hospital]. AB - BACKGROUND: The registration book for admission and discharge of patients was the basis of a survey of hospital morbidity and the main source of information concerning the diseases attended in the hospitals in Spain. The aim of this study was to evaluate the quality of this information from the data of a hospital with a computerized patient registration system. METHODS: The sample collected from the registration book in 1985 by the National Institute of Statistics studied three types of errors: the main error being selection of diagnosis, coding and transcription of the principal diagnosis, and comparison of data contained in the patient discharge form. RESULTS: In the 896 releases studied an error oscillating between 1 and 2% was found in transcription. The principal diagnosis had been erroneously selected in 26% of the reports with more than one diagnosis. Important coding errors were found in 11%. Transfer between different hospital wards or death were variables found to increase the probability of error. CONCLUSIONS: Hospital registers should be submitted to quality control processes in which the physicians facilitating the data should participate. PMID- 1602867 TI - [Consistency of the histologic diagnosis of Lauren's classification of gastric cancer]. AB - BACKGROUND: Lauren's classification of gastric cancer is usually followed in epidemiological studies thus requiring evaluation of its reproducibility. This classification defines 2 principal histological types: intestinal and diffuse with different proportions in high and low risk areas possibly being associated to different causal factors. METHODS: The concordance diagnosis in an aleatory sample of 81 gastric carcinomas stratified according to the participation of 14 hospitals in an epidemiological study of 354 cases and 354 controls was analyzed. The initial diagnosis carried out was compared by more than 20 pathologists with the reclassification diagnosis by consensus of 2 pathologists by the proportion of agreement or concordance observed in the kappa index. Keeping the final reclassification by consensus as a reference, sensitivity, specificity and predictive values were also calculated. RESULTS: The proportion of concordance observed was of 78% for the intestinal and 90% for the diffuse with a kappa index of 0.55 and 0.74, respectively. Sensitivity for the intestinal type was of 88% and for the diffuse 81% with specificity being of 67% in the intestinal and 93% in the diffuse. CONCLUSIONS: Subjectivity in the interpretation of certain parameters necessary for histological diagnosis may be reduced by the elaboration of protocols in which the principal histological criteria to follow are detailed. Nonetheless, the distinction made between the two principal types, intestinal and diffuse, is valid enough to be used in multicenter epidemiological studies and in comparative studies. PMID- 1602866 TI - [Prevalence of lipid disorders and their course after blood pressure control in essential arterial hypertension]. AB - BACKGROUND: Arterial hypertension and hyperlipidemia are the principal factors of cardiovascular risk with an association which appears to obey common pathogenic bonds. In the present study the initial prevalence of hypercholesterolemia and hypertriglyceridemia was determined in a sample of essential hypertensives and the long term effect of different antihypertensive treatments on lipid metabolism has been analyzed. METHODS: Total cholesterol, its LDL and HDL fractions and plasmatic triglycerides were determined in a sample of 158 hypertensive patients prior to the initiation of antihypertensive treatment and following one year of normotension. RESULTS: The initial prevalence of lipid disturbances was of 47% (isolated hypercholesterolemia 17%, isolated hypertriglyceridemia 14% and mixed anomalies 16%). After one year of tension control the initial prevalence was not modified. In the patients controlled with a low sodium diet a decrease in total cholesterol and an increase in cholesterol-HDL were observed in those treated with atenolol, and a decrease in cholesterol-LDL was seen in those receiving captopril. The group treated with nifedipin presented no significant variations of the lipid profile. CONCLUSIONS: The prevalence of lipid disturbances is greater among the hypertensive patient than in the general population. The rational treatment of a hypertensive patient must not only regard blood pressure figures but also control the other risk factors since the drugs commonly used in the treatment of arterial hypertension generally demonstrate a neutral effect on lipid metabolism. PMID- 1602868 TI - [Treatment of pain in the patient with arthrosis]. PMID- 1602869 TI - [Ambulatory surgery. A solution?]. PMID- 1602870 TI - [Renal vasculitis without hematuria in senile patients]. AB - Systemic vasculitis is a disease whose prognosis has improved considerably with steroid and immunosuppressive treatment, which points up the importance of early diagnosis. In elderly, diagnosis is made more difficult because the frequent onset in the form of a febrile syndrome with non-specific disturbances in general condition. In these patients it is not uncommon that a kidney involvement is what leads to diagnosis of the disease. Hematuria is almost a constant in vasculitis nephropathy. In their absence, acute renal failure in elderly is usually attributed to hemodynamic causes and the frequent presence of iatrogenic tubular factors. This is a report on the case of three elderly patients who presented a febrile syndrome with asthenia, anorexia and weight loss. The three cases progressed to acute renal failure with no disorders in urinary sediment. In two cases was a history of administration of gentamycin, indomethacin and iodated contrast. The clinical diagnosis was toxic and ischemic tubulopathy and, when dialysis became necessary, a renal biopsy was done which showed granulomatous vasculitis, intersticial nephritis and in two cases, necrotizing glomerulitis and crescent formation. Treatment with steroids and cyclophosphamide was started which improved general condition and renal function in one case. Early renal biopsy is advisable in senile patients with non specific systemic symptoms and progressive acute renal failure of unclear origin, even when hematuria is lacking. In this setting, the appearance of underdiagnosed renal vasculitis is possible, and consequent immunosuppressive treatment is a factor for consideration. PMID- 1602871 TI - [Assessment of the functional capacity in patients with chronic heart insufficiency]. PMID- 1602872 TI - [Neurobiologic perspectives of attention deficit disorder with hyperactivity]. PMID- 1602873 TI - [Liver abscess caused by Salmonella typhi associated with splenic ischemic necrosis and renal vein thrombosis]. PMID- 1602874 TI - [Hepatitis C in hemodialyzed patients and with renal transplantation]. PMID- 1602875 TI - [Lactobacillus and tuberculous empyema]. PMID- 1602876 TI - [Adverse reactions to parenterally administered iodinated contrast media]. PMID- 1602877 TI - [Renal embolism caused by cholesterol crystals: late onset of renal insufficiency]. PMID- 1602878 TI - [Acute organophosphate insecticide poisonings in the province of Almeria. A study of 187 cases]. AB - BACKGROUND: The aim of the present study was to analyze the epidemiological and clinical characteristics of poisoning by organophosphorus insecticides in the province of Almeria. METHODS: One hundred eighty-seven patients diagnosed with organophosphorus insecticide poisoning were included from 1981-1986. In all the cases a previously established clinic and therapeutic protocol was applied. RESULTS: Eighty-six percent of the patients were males with a mean age of 31 years. The poisoning was accidental in 62% of the cases and attempted suicide in 38%. The via of absorption was cutaneous-respiratory in 57% and digestive in 43% of the patients. All the patients presented florid initial cholinergic symptomatology. The presence of bronchorrhea, tremor-fasciculations, respiratory depression and diminution in the level of conscience was associated with severe intoxication. The quantification of acetylcolinesterase was useful as a diagnostic parameter. Global mortality was 4%. Ten percent of the patients developed delayed signs of neurotoxicity. CONCLUSIONS: The high hospital demand for poisoning by organophosphorus insecticide is of note. Hospital mortality is low. The severity of intoxication is related with attempts of autolysis, digestive absorption, appearance of respiratory manifestations and of the central nervous system and the development of complications. PMID- 1602879 TI - [Echocardiography with intravenous dipyridamole infusion in the assessment of ischemic cardiopathy. A comparison with the stress test]. AB - BACKGROUND: Diagnosis of ischemic cardiomyopathy by noninvasive methods is a challenge for the clinician. Echocardiography with intravenous administration of dipyridamole has been proposed as an alternative to exercise stress test in this setting. METHODS: Intravenous administration of dipyridamole (0.84 mg/kg in 6 minutes) with two-dimensional echocardiography and 12-lead electrocardiographic monitoring was performed in 50 patients. The test was considered positive when contractility of any of the left ventricular segments decreased, at least, one grade. In that moment, dipyridamole administration was stopped and aminophylline (40-240 mg over 1 to 3 minutes) was given. All patients underwent exercise stress test and coronary angiography. RESULTS: Significant coronary artery disease (70% stenosis in, at least, one of the major vessels) was demonstrated in 32 patients. Twenty of these had a positive dipyridamole echocardiography test (62%) and 23 had a positive exercise stress test (71%). None of the patients without significant coronary artery disease had a positive dipyridamole echocardiography test and 5 patients (23%) has a positive exercise stress test. Dipyridamole echocardiography test had and overall sensitivity of 60% and a specificity of 100%. Exercise stress test had an overall sensitivity of 75% (NS) and a specificity of 67% (p less than 0.01). Dipyridamole echocardiography test was well tolerated: there were no complications during the test. One patient had a transitory type I second-degree AV block. CONCLUSIONS: Dipyridamole echocardiography is a high specificity test for coronary artery disease and has a similar sensitivity than exercise stress test. It is well tolerated and in the authors' experience there were no complications. PMID- 1602880 TI - [The use of the potential years of life between the ages of 1 and 64 as an indicator of premature mortality in Aragon during 1987]. AB - BACKGROUND: Years of potential life lost (YPLL) are a health indicator which allows to discriminate the main causes of premature mortality weighting up the deaths according to the age of dead person. METHODS: Premature mortality in Aragon during 1987 is analysed by means of the indicator YPLL between the ages 1 and 64 years. The information given by this indicator along with that supplied by the mortality rates is used to obtain a more complete information of the role and relative importance of each one of the main groups of diseases of the International Classification of Diseases (ICD-9th revision) within the mortality in Aragon during that whole year. RESULTS: The biggest rates of YPLL by one thousand population were due to tumours (9.87), traumatisms and poisonings (8.84), vascular diseases (5.65) and digestive diseases (1.96). Mortality and YPLL rates were higher for males than for females and statistically significant differences were also observed when comparing the provinces of Zaragoza and Huesca with the province of Teruel (higher rates in the first ones) and when comparing rural with urban areas (higher rates in the second case). CONCLUSIONS: According to this indicator the preventive programs in Aragon should lead to the prevention of tumors, traumatisms, vascular diseases and digestive diseases, without forgetting that these illnesses have a bigger effect on male population and on urban areas. PMID- 1602882 TI - [Has the strategy in the early detection of colorectal cancer changed?]. PMID- 1602881 TI - [Respiratory insufficiency in acute pancreatitis]. AB - BACKGROUND: Acute respiratory failure (ARF) is one of the systemic complications of acute pancreatitis (AP). The severity of AP may be objectified by the Ranson index and the radiologic alterations showed by abdominal computerized tomography (CT). The aim of the present was to study the relation between both problems. METHODS: Two hundred ninety-five cases of AP attended between November 1983 and August 1987 were revised. Ranson criteria were used to qualify the 295 AP and the abdominal CT in 85 cases. ARF was defined as PaO2 less than 60 mmHg breathing air at room temperature. The severity of ARF was classified by the respiratory index (RI: PaO2/FIO2) with ARF being considered as severe when less than 200. In 100 cases of AP the thoracic radiologic alterations were objectified and evaluated in order to know their relation with ARF. RESULTS: ARF was the most frequent complication (28%) of AP, being severe in 8%. Pleural effusion was the radiologic alteration most frequently observed (23 patients). In 28% there was no correlation between the radiology and the presence of ARF. The correction of ARF was achieved in 85% of the patients with a mask of O2 less than 40%. Mean ARF was 227. A correlation was found between ARF and the severity of the episode of AP and the changes observed in the abdominal CT. CONCLUSIONS: Acute respiratory failure is the most frequent complication of acute pancreatitis and correlates with the severity of the episode of the latter; classification of the episode of acute respiratory failure by respiratory index is of use. PMID- 1602883 TI - [Organophosphate poisoning: the current focus of this clinical entity]. PMID- 1602884 TI - [The epidemiology of colorectal cancer]. PMID- 1602885 TI - [Pulmonary mucormycosis with cutaneous metastasis]. PMID- 1602887 TI - [Liver abscesses due to Ascaris lumbricoides]. PMID- 1602886 TI - [Hypothermia associated with erythromycin]. PMID- 1602888 TI - [Thyroiditis of probable tubercular etiology and the recurrence of Graves-Basedow disease]. PMID- 1602889 TI - [Interleukin-6 and multiple myeloma]. PMID- 1602890 TI - [The association of acute gouty arthritis and arthritis due to penicillin resistant gonococcus]. PMID- 1602891 TI - [Serum aminoterminal procollagen type-III peptide in the diagnosis of chronic hepatopathies]. AB - BACKGROUND: The aims of the present study were to 1) compare the serum levels of the aminoterminal peptide of procollagen type III (PIIIP) in patients with different chronic liver diseases, 2) correlate their concentrations with histologic features in liver biopsy and 3) evaluate their use in the diagnosis of liver diseases and in recognition of fibrosis. METHODS: With these aims PIIIP was determined in 57 patients with different chronic liver diseases and in 50 healthy donors. RESULTS: PIIIP was significantly elevated in patients with chronic active hepatitis (18.3 +/- 5.5 ng/ml; p less than 0.01) and with liver cirrhosis (27.8 +/- 11.7 ng/ml; p less than 0.001). The serum levels of this peptide related significantly with the severity of liver disease (p less than 0.001) in addition to the degree of morphometric liver fibrosis (Rs: 0.736; p less than 0.001) and with the degree of histologic activity (Rs: 0.78; p less than 0.001). The correlation between PIIIP and fibrosis was due to the relation between the same and inflammation. The levels of this peptide which were higher than 15 ng/ml were a sensitive test for the diagnosis of active liver disease (0.80) and cirrhosis (0.87) permitting differentiation between chronic and persistent active hepatitis. The differentiation between chronic active hepatitis and cirrhosis was only possible when 24 ng/ml were taken as a discriminative level. CONCLUSIONS: The comparison of serum levels of the aminoterminal peptide of procollagen type III (PIIIP) in patients with different chronic liver diseases can predict moderate or high degrees of inflammatory activity when PIIIP are higher than 15 ng/ml. This test is of use for evaluating chronic hepatopathies although the levels reflect the activity of inflammation better than the degree of hepatic fibrosis. PMID- 1602892 TI - [Brucellosis after treatment: the diagnosis of recurrences]. AB - BACKGROUND: Given the frequency of relapse following treatment of brucellosis as well as the persistence of symptoms the authors attempted to discover a recommendable position for surveillance of patients once treatment has been completed. METHODS: A series of 105 patients treated for brucellosis was prospectively analyzed, 11 of whom had relapse. Post treatment symptoms, serology titers and the results of the cultures between the cured patients and those with relapse were compared. RESULTS: Hemocultures (sensitivity 0.73) and "specific" symptoms (prolonged fever, spondylitis, arthritis, orchitis and others) were the most useful data for diagnosis of relapse. The presence of vague symptoms following treatment was of slight value specially in the first months. Elevation of serology titers following treatment offered little aid in diagnosis (likelihood ratio 1.7). The persistence of high titers of serology several months following completion of treatment offered high likelihood ratios which may aid in therapeutic decision making. CONCLUSIONS: It is recommended that no tests be made on asymptomatic patients following treatment of brucellosis and to treat those patients with "specific" symptoms. Hemocultures are recommended for patients with vague symptoms and if several months have passed serology should be carried out from which the probability of relapse may be calculated. PMID- 1602893 TI - [The computerization of the clinical history in an internal medicine service]. AB - BACKGROUND: The following objectives were studied in the implementation of computerization in the registration of clinical histories: gather all the information obtainable from the patient, be able to up-date the information once introduced, use of the information by health care personnel, automatic carrying out of all routine reports, elaboration of hospital indexes, follow the conventional model of clinical history as much as possible and reasonable price. METHODS: The study was carried out in a 40-bed department of internal medicine in a county hospital. A mixed system of partial coding was used combined with free texts, the latter being with no limit of space. The clinical histories were structured in 9 groups which covered from personal data to complementary explorations. A personal computer compatible "AT" was employed. The program was designed and analyzed by internal medicine doctors using CLIPPER and language "C". RESULTS: The thousand one hundred histories were opened with the space occupied in the disc being of 7 Megabytes. Following the premise of: "write all data only once", the obtaining of all type of documents, indexes and listed was automatized facilitating the knowledge of the working of the department directly. Adaptation by medical personnel was good. CONCLUSIONS: The model presented achieved the previously mentioned aims of information gathering and up-dating, use of the information by hospital personnel, automatization of routine reports and indexes, the following of conventional models and economic feasibility. Computerization should not be imposed, must not represent more work and advantages should be obtained by its use. PMID- 1602894 TI - [The significance of aminoterminal procollagen type-III peptide in chronic hepatopathies]. PMID- 1602895 TI - [Chronic granulomatous disease, 1992]. PMID- 1602896 TI - [Chronic granulomatous disease and pulmonary nocardiosis]. AB - A 19-years-old male was admitted for left bilobar pneumonia. All microbiologic studies in blood and in several samples obtained by bronchoscopy were negative. The patient worsened progressively despite antibiotherapy of a wide spectrum. A fine needle transparietal puncture was performed. The cultures of the sample were positive for Nocardia asteroides, a positive catalase germ. Immunologic studies initiated after this time showed negative tetrazolium nitroblue test, the results of which led to the diagnosis of chronic granulomatous disease. This disease is very infrequent and the polymorphonuclear leukocytes are genetically incapable of producing peroxides whose absence impedes lysis of the positive phagocytic catalase germs with which a histologic reaction is produced in the form of granulomas from which the name of the disease is derived. PMID- 1602897 TI - [Monoclonal antibodies and differentiation antigen groups: study methods and their applications to diagnostic use]. PMID- 1602898 TI - [Uterine leiomyoma: a benign neoplasm with pulmonary metastases]. PMID- 1602899 TI - [Raynaud's phenomenon and pulmonary adenocarcinoma]. PMID- 1602900 TI - [Septic arthritis in cirrhotic patients]. PMID- 1602901 TI - [The intradiscal injection of triamcinolone hexacetonide: from alternative to abandonment]. PMID- 1602903 TI - [Arterial hypertension. The standardization of the diagnostic criteria]. PMID- 1602902 TI - [Thyroid lymphoma. A medical emergency]. PMID- 1602904 TI - [The prevalence of tetanus antibodies in the adult population of Catalonia]. AB - BACKGROUND: The aim of this study was to know the immune state of the adult population of Catalonia (Spain) versus tetanus. METHODS: The prevalence of antitetanic antibodies was determined in a representative sample (n = 604) of this population group (greater than or equal to 15 years). The technique used as that of passive hemagglutination reaction. The field work was carried out during 1989. RESULTS: 37.7% of the males and 15.7% of the females (p less than 0.001) presented titres of protector antibodies (greater than or equal to 0.01 Ul/ml) versus tetanus. The prevalence of antibodies was higher in youths of either sex and progressively descended with age. No statistically significant association was found upon performance of multivariate analysis between the sociodemographic variables (place of birth, level of education, residence, social class) and the prevalence of antibodies. CONCLUSIONS: The results of this study demonstrate that antitetanic vaccination currently being undertaken is not sufficient to insure adequate protection during adult life thus potentiating the need for the vaccination of adults in Catalonia. PMID- 1602905 TI - [Spanish scientific production in food and nutrition from 1987 to 1990]. AB - BACKGROUND: The aims of this study were: to quantify the Spanish scientific production with international repercussion, to determine the degree of world diffusion and the participation of the different autonomic communities and the organisms implicated with reference to the area of sciences of alimentation and nutrition between 1987 to 1990. METHODS: Articles published during this period of time were selected by the Medline system, delimiting Spanish production. The articles selected were classified according to autonomic communities and institutions and in relation to the subsection of the area in question. The impact factor obtained from the Science Citation Index was used as an indicator of scientific diffusion. The autonomic communities of Catalonia and Madrid made up almost 50% of the scientific production between 1987 and 1989 with greater participation being observed from the other communities in 1990. The institutions of greatest scientific contribution were the medical and science schools. Thirty percent of the articles referred to experimental nutrition and toxicology of alimentation. CONCLUSIONS: a) Spanish participation in the diffusion of scientific studies on nutrition is similar to global participation in medical sciences, b) in 1990 an attenuation was detected in the differences existing in the degree of participation by the autonomic communities in the national scientific production; c) the schools of Medicine make up the institutions with greater relevance in scientific production while this activity is not reflected within the hospitals. PMID- 1602906 TI - Pulmonary sequelae of intraparenchymal bismuth subgallate. AB - Bismuth subgallate (BSG) is a heavy metal compound which is effective in lowering the incidence of hemorrhage after adenotonsillectomy and has been demonstrated to activate Factor XII. In a minority of children, the paste has been suctioned from the cuffless oral endotracheal tube after adenotonsillectomy. No pulmonary sequelae have been noted in these patients. To assess the effect of BSG aspiration, 75 rats were divided into groups receiving either intratracheal BSG or saline. Early and late parenchymal effects were documented at 5 and 30 days following administration. Although there were no differences in the general well being, activity level, or weight in these rats, acute pneumonia followed by a histiocytic, foreign-body response was noted in a significant number of rats in the BSG group. Although no clinical pulmonary sequelae of BSG use have been noted in our patients, this information should alert clinicians to the risks of BSG use in the pulmonary-compromised patient, and encourage them to either employ all methods of preventing aspiration in such patients when using BSG, or to use another hemostatic modality for the utmost safety. PMID- 1602907 TI - Pediatric temporal bone fractures. AB - Twenty-seven temporal bone fractures in 25 pediatric patients were evaluated over a 6-year period. The diagnosis was confirmed with otoscopy and high-resolution computed tomography scans (HRCT). Three-dimensional reconstruction of high resolution computed tomography scans were used to aid in the diagnosis. The most common fracture was an oblique fracture which is oriented in an axial or horizontal plane with the temporal bone. Facial nerve paralysis was found in 6 of our patients, which is less than the expected incidence when compared to adults. Hearing loss was found in 24 patients, the most common of which was conductive hearing loss, which had a higher incidence than expected when compared with adults. PMID- 1602908 TI - Uvulopalatopharyngoplasty for obstructive sleep apnea: a community's experience. AB - Uvulopalatopharyngoplasty (UPPP) has become an accepted method for treating obstructive sleep apnea (OSA), with a reported success rate as high as 77%, depending upon inclusionary and outcome criteria. The authors reviewed the records of 90 patients with moderately severe OSA (apnea plus hypopnea index [AHI] greater than 20) who underwent UPPP at either a private community or an academic hospital. Forty percent of patients experienced more than a 50% reduction in their AHI with UPPP. Only 22 (24%) of the patients had a postoperative AHI less than 50% of the preoperative AHI and less than 20, i.e., met the authors' criteria for surgical success. The success rate for community otolaryngologists was no different than that achieved in the academic institution. When data from previously published reports were analyzed using these criteria for success, similar results were observed. This study suggests that the effectiveness of UPPP performed by the general otolaryngologic community is equivalent to that reported in the literature. However, more rigorous criteria must be applied to UPPP when evaluating its results and in counseling potential candidates for this procedure. PMID- 1602909 TI - Tympanic electrocochleography for evaluation of endolymphatic hydrops. AB - There has been increased interest in electrocochleography for the diagnosis and intraoperative monitoring of patients with endolymphatic hydrops. Attention has been focused on the determination of the summating potential:action potential (SP:AP) ratio from alternating polarity clicks. Review of this technique at the University of Minnesota led to a reevaluation of the usual interpretation of these recordings. Separate examination of the rarefaction and condensation click recordings provides insight into abnormal response patterns. Cases are presented to illustrate a variety of normal and abnormal patterns including abnormal differences in the latency of condensation and rarefaction-click-generated action potentials, increased summating potential, uncanceled cochlear microphonic, and reduced action potential and summating potential amplitudes. These response categories may be useful in understanding the pathophysiology of Meniere's disease. PMID- 1602910 TI - Complementary use of computed tomography and magnetic resonance imaging in assessing skull base lesions. AB - Twenty-six patients underwent computed tomography (CT) and magnetic resonance imaging (MRI) of skull base lesions at the Cleveland Clinic Foundation. CT provided improved bone detail, documenting invasion of the lamina papyracea, orbital floor, fovea ethmoidalis, cribriform plate, pterygoid plates, hard palate, and skull base. MRI defined invasion of the orbit, dura, brain, and cavernous sinus. Improved soft-tissue-tumor interface was evident on MRI. MRI was superior to CT in determining carotid artery involvement. MRI distinguished between tumor and retained secretions in the paranasal sinuses. Combining radiographic tumor staging reliably predicted surgical findings; however, MRI consistently yielded sufficient diagnostic information and the additional expense of performing two imaging procedures may not be justified. PMID- 1602911 TI - Concomitant chemoradiotherapy with cisplatin, 5-fluorouracil and hydroxyurea in poor-prognosis head and neck cancer. AB - Based on encouraging results with 5-fluorouracil (5-FU), hydroxyurea, and concomitant radiotherapy in patients with advanced or recurrent head and neck cancer, an attempt was made to modulate the regimen by the addition of cisplatin as a third active agent. A cohort of 26 patients with head and neck cancer of all histologies were entered into a broad phase I study investigating simultaneous radiation therapy, 5-FU (with or without leucovorin), HU, and infusional cisplatin administered on an alternate-week schedule. Eleven patients (group 1) had failed prior curative local therapy and 15 patients (group 2) were considered to have a poor prognosis with standard therapy. The median follow-up was 30 months. The response rate for all evaluable patients was 82% (14/17), and the complete response rate was 65% (11/17). Patients in group 1 demonstrated a high failure rate (9/11), while few group 2 patients failed after treatment (2/15). The median time to progression was 4.4 months in group 1 and has not been reached in group 2. Patients in group 1 failed locally (7/11), while no local failures were observed in group 2. Acute and cumulative hematologic toxicity was encountered at all dose levels and schedules tested and prevented escalation of the cisplatin dose beyond the desired level of 100 mg/m2 per months. Mucositis was a second significant toxicity in patients with head and neck cancer and was more pronounced during cycles containing leucovorin. A detailed analysis of survival, time to progression, and site of failure is presented. PMID- 1602912 TI - The suprahyoid approach for squamous cell carcinoma of the base of the tongue. AB - The suprahyoid pharyngotomy is a well-recognized surgical approach to the base of the tongue. However, its use has been widely criticized for squamous cell carcinomas. Some surgeons believe this approach offers limited exposure and that violating the preepiglottic space increases the risk of recurrence. A retrospective study of squamous cell carcinoma of the base of tongue was carried out to address these surgical concerns. Nineteen patients presented with T1 or T2 lesions, 13 of whom underwent suprahyoid pharyngotomy with neck dissection. Those with nodal disease underwent adjunctive irradiation therapy and those with extracapsular spread also received subsequent adjuvant chemotherapy. At present, all patients are disease free. The suprahyoid pharyngotomy is an ideal surgical approach in the management of T1 or T2 squamous cell carcinoma of the base of tongue. PMID- 1602913 TI - Noise-induced hearing loss in children. AB - Occupational noise exposure remains the most commonly identified cause of noise induced hearing loss (NIHL), but potentially hazardous noise can be encountered during leisure-time activities. NIHL in the pediatric population has received scant attention. This study focuses on 114 children and adolescents (ages 19 and under: 90.3% males) who were diagnosed as having probable NIHL on the basis of history and audiometric configuration. In 42 children the loss was unilateral, while the remaining 72 had sensorineural losses of varying configurations in the contralateral ear. The mean age of referral for evaluation was 12.7 years (range 1.2 to 19.8, SD 4.21), although 26% of these losses were diagnosed in children aged 10 years and younger. Such irreversible, but potentially preventable losses, should be given high priority on the public health agenda. Comprehensive, age appropriate educational programs must be developed for elementary and secondary students and their parents to acquaint them with potentially hazardous noise sources in their environment. PMID- 1602914 TI - Intracranial complications of mucormycosis: an experimental model and clinical review. AB - The clinical course of patients with mucormycosis of the paranasal sinuses can be unpredictable and is often determined by intrinsic host factors. The degree to and mechanism(s) by which these factors influence a patient's ability to survive the disease are poorly understood. Extensions to orbital and intracranial structures occur in some patients with paranasal sinus mucormycosis despite aggressive treatment. Controversies persist over adequate antifungal regimen, the precise role of hyperbaric oxygenation, and the appropriate extent of surgical debridement. We have developed an alloxan-induced immunocompromised murine model of mucormycosis in mice. Deferoxamine iron chelation produced rhinocerebral mucormycosis in these animals when challenged intraethmoidally with Rhizopus spores. The implications of our experimental studies in the content of our clinical experience in managing patients with intracranial extensions of paranasal sinus mucormycosis are discussed. PMID- 1602915 TI - The early stages of polyp formation. AB - The purpose of this study is to describe polyp formation in the mucosa of the middle ear as a possible model for the pathogenesis of nasal polyps. In 65 Wistar rats, the eustachian tube was occluded on the left side for up to 20 months; 60 right-sided, nonoccluded ears served as controls. Following occlusion, the middle ear mucosa was examined for signs of polyps. Signs of polyp formation or fully developed polyps were seen in 14 (22%) of the middle ears, and were only seen in middle ears with signs of actual or previous infection. It was established that the first stages of polyp formation include epithelial rupture, proliferation of fibrous tissue through the epithelial defect, and epithelialization of the prolapsed fibrous tissue by proliferation and migration of epithelial cells from the surrounding epithelium until there is full epithelial covering of the polyp. This report discusses whether the described middle ear model may form basis for the explanation of the pathogenesis of nasal polyps. PMID- 1602916 TI - Hearing prognosis and intraoperative guidance of brainstem auditory evoked potential in microvascular decompression. AB - Intraoperative monitoring of brainstem auditory evoked potential (BAEP) was done in 34 patients submitted to microvascular decompression (MVD). Seventeen of these patients had trigeminal neuralgia, and 17 had hemifacial spasm. Transitory postoperative hearing loss was observed in 6 (18%) of the patients, and permanent hearing loss was observed in 2 (6%) of the patients. Wave I-V interpeak latency (IPL) was calculated during each step of the MVD procedure in order to identify the dangerous steps of the surgery. Wave I-V IPL abnormalities occurred more frequently during cerebellar retraction. Of the 6 patients who had total loss of BAEP lasting throughout the surgery, 1 (17%) had definitive deafness. Ten of the 34 patients had an absence or partial diminution of BAEP without total normalization before the end of surgery. Among these 10 patients, 2 had transitory hearing loss and 1 had permanent hearing loss. PMID- 1602917 TI - Effects of bacterial endotoxin applied to the guinea pig cochlea. AB - The ototoxic potential of bacterial endotoxin present in middle ear effusions was evaluated by inoculating endotoxin solutions of 10 micrograms/mL or 1000 micrograms/mL directly into the scala tympani of the guinea pig cochlea. Median auditory brainstem response threshold shifts of 12.5 and 20 dB were observed in the experimental ears exposed to the higher dose at days 2 and 4, respectively, with gradual improvement to near baseline by day 28. Histologic examination revealed inflammatory infiltrates in the scala tympani and scala vestibuli of several of these cochleas. The lower concentration, closer to that found in human effusions, elicited no significant loss of hearing and a milder inflammatory response. It is concluded that brief exposure of the cochlea to endotoxin from middle ear effusions is insufficient to cause hearing loss. Under chronic conditions, however, persistent inflammation within the cochlea may result in a sensorineural deficit. PMID- 1602918 TI - Drill-generated sensorineural hearing loss following mastoid surgery. AB - Drilling during mastoid surgery may result in temporary noise-induced hearing loss. This has practical implications for both the patient and surgeon. In a prospective study of 40 patients, audiometric testing was done both preoperatively and postoperatively to try to detect any significant hearing loss in the immediate postoperative period. The data were analyzed using the Student's paired t test. No statistically significant difference was found. A sensorineural hearing loss soon after mastoid surgery is not due to the noise generated by the drill. In the event of any hearing loss during this period, other causes should be sought. PMID- 1602919 TI - Neural regeneration in the noise-damaged chinchilla cochlea. AB - Recent studies in the bird ear have shown that degenerated hair cells are sometimes replaced by regenerated receptor cells. The present study evaluated the adult mammalian cochlea for evidence of hair-cell and nerve-fiber regeneration. Eighty-eight noise-damaged chinchilla cochleas were examined as plastic-embedded whole mounts by phase-contrast and bright-field microscopy. No signs of hair-cell regeneration were found. However, 32 (70%) of 46 cochleas damaged by high intensity noise and 20 (48%) of 42 cochleas damaged by moderate-intensity noise contained a variable number of nerve fibers which appeared to be regenerated. These fibers, which were located in severely damaged areas of organ of Corti, differed from residual fibers with respect to their diameters, the degree and pattern of myelination, and by the abnormal paths they followed within the osseous spiral lamina and on the basilar membrane. The number of regenerated fibers varied with type of exposure and length of recovery. The strongest response was found in ears exposed to a high-intensity, low-frequency noise. The results described here indicate that a potential exists for the biological restoration of the mammalian inner ear. PMID- 1602920 TI - Predictive value of objective esophageal insufflation testing for acquisition of tracheoesophageal speech. AB - This prospective study was undertaken to assess the predictive value of esophageal insufflation on the acquisition of tracheoesophageal (TE) speech. Fourteen total laryngectomy patients were evaluated prior to tracheoesophageal puncture (TEP) using objective esophageal pressure measurements. These patients then were followed prospectively for 6 to 13 months. Speech was assessed at the time of prosthesis fitting, at 1 month, at less than 6 months, and at greater than 6 months post-TEP. No patient underwent pharyngeal myotomy. Pre-TEP esophageal insufflation pressure was associated (P = .065) with successful TE speech at the time of prosthesis fitting, but was not associated with successful TE speech acquisition after 6 months. This study's results suggest that patients with poor pre-TEP esophageal insufflation test results will usually obtain successful TE speech given adequate time and training, even without pharyngeal myotomy. PMID- 1602922 TI - Endoscopic treatment of frontal sinusitis. PMID- 1602921 TI - Combined approach middle meatal antrostomy. PMID- 1602923 TI - False vocal cord reconstruction of the glottis following vertical partial laryngectomy: a preliminary analysis. PMID- 1602924 TI - Cochlear nucleus stimulation. PMID- 1602925 TI - Microvascular oromandibular reconstruction. PMID- 1602926 TI - Complications of operative and endoscopic gastrostomies. AB - In a retrospective study of fifty cases of gastrostomy insertion performed operatively (OG) or using a percutaneous endoscopic approach (PEG), complication rates were 74 percent (nineteen adults) and 76 percent (seventeen children) in the OG group, and 86 percent (fourteen adults) in the PEG group. While most complications were minor, major ones were usually related to the underlying disease and the general condition of the patient. PMID- 1602927 TI - Strategies to reduce the high cost of patient noncompliance. AB - The documented low rate of compliance can result from ineffective communication by the pharmaceutical and medical profession, and poor comprehension of prescription instructions by the public. Presented are several examples of how pharmacists can assist physicians in improving and monitoring their patients' compliance behavior. Strategies to enhance communication through the written prescription are offered. PMID- 1602928 TI - Community hospital implementation of intraaortic balloon pump therapy for complicated myocardial infarction. AB - The intraaortic balloon pump may be employed in the community hospital setting to stabilize complicated acute myocardial infarction, even in the presence of thrombolytic therapy. PMID- 1602929 TI - Hypertriglyceridemia: severe type V hyperlipidemia in a young woman. AB - We present a patient with the typical clinical and biochemical features of severe Type V hyperlipidemia associated with alcohol consumption and estrogen use. Prompt medical intervention resulted in normalization of her lipid profile. We review the lipoprotein composition, the role of lipoproteins in lipid transport with special emphasis on triglycerides, and the clinical features, pathogenesis, and management of Type V hyperlipidemia. PMID- 1602930 TI - Gastrointestinal surgery for severe obesity: a response. PMID- 1602931 TI - Gestational diabetes mellitus. PMID- 1602932 TI - Imaging case of the month. Arnold-Chiari I malformation with syringomyelia. PMID- 1602933 TI - Cancer prevention. PMID- 1602934 TI - Epidemiology & Disease Control Program. OSHA final rule on occupational exposure to bloodborne pathogens. March, 1992. PMID- 1602935 TI - The blood pressure response to exercise in anabolic steroid users. AB - We measured blood pressure at rest and during exercise in nine weight lifters using anabolic steroids, 10 weight lifters not using these drugs, and 10 sedentary controls. BP was measured using standard sphygmomanometry and an appropriately sized cuff. Maximal treadmill tests and leg press exercise were conducted in random order on separate days. Systolic blood pressure in the anabolic steroid users was higher at rest and during both forms of exercise. Diastolic blood pressure during exercise was also higher in the anabolic steroid users than in the other two groups. The maximal systolic and diastolic blood pressure change from rest to exercise was not different among the groups, suggesting that the higher exercise pressure in the drug users was primarily due to higher resting values. Body weight and biceps circumference were greatest in the anabolic steroid users. Adjusting rest and exercise blood pressure for body weight or biceps size eliminated statistically significant differences between groups, but had little impact on the absolute group differences. We conclude that the higher rest and exercise blood pressure values noted in anabolic steroid users may be related to their larger body mass or may be an artifact of the larger arm circumference in these subjects. Other factors may also be operative, however, because blood pressure remained nonsignificantly higher even after body weight and biceps size were adjusted for statistically. PMID- 1602936 TI - Current concepts concerning thirst, dehydration, and fluid replacement: overview. AB - For healthy endurance athletes, two potentially life-threatening medical emergencies are dehydration-mediated heat injuries and hyponatremia. Likewise, dehydration reduces exercise performance via thermoregulatory and cardiovascular impairment as well as electrolyte imbalances. Authors of this symposium integrate new research findings with established concepts concerning the development of dehydration (body water deficit), the physiological and medical consequences of fluid imbalance, and fluid (volume and composition) replacement strategies that minimize the risk of medical emergencies and optimize exercise performance. The following papers provide the readers with an appreciation of the historical development of current concepts and offer an informed opinion concerning fluid replacement strategies for a variety of work performance athletic events. PMID- 1602937 TI - Problem: thirst, drinking behavior, and involuntary dehydration. AB - The phenomenon of involuntary dehydration, the delay in full restoration of a body water deficit by drinking, has been described extensively but relatively little is known about its physiological mechanism. It occurs primarily in humans when they are exposed to various stresses including exercise, environmental heat and cold, altitude, water immersion, dehydration, and perhaps microgravity, singly and in various combinations. The level of involuntary dehydration is approximately proportional to the degree of total stress imposed on the body. Involuntary dehydration appears to be controlled by more than one factor including social customs that influence what is consumed, the capacity and rate of fluid absorption from the gastrointestinal system, the level of cellular hydration involving the osmotic-vasopressin interaction with sensitive cells or structures in the central nervous system, and, to a lesser extent, hypovolemic angiotensin II stimuli. Since humans drink when there is no apparent physiological stimulus, the psychological component should always be considered when investigating the total mechanisms for drinking. PMID- 1602938 TI - Physiological consequences of hypohydration: exercise performance and thermoregulation. AB - During exercise in the heat, sweat output often exceeds water intake, which results in a body water deficit or hypohydration. This water deficit occurs from both the intracellular and extracellular fluid compartments, and causes a hypertonic-hypovolemia of the blood. Aerobic exercise tasks are likely to be adversely affected by hypohydration; and the warmer the environment the greater the potential for performance decrements. Hypohydration causes greater heat storage and reduces one's ability to tolerate heat strain. The greater heat storage is mediated by reduced sweating rate (evaporative heat loss) and reduced skin blood flow (dry heat loss) for a given core temperature. Reductions of sweating rate and skin blood flow are most tightly coupled to blood hypertonicity and hypovolemia, respectively. In addition, hypovolemia and the displacement of blood to the skin make it difficult to maintain central venous pressure and thus an adequate cardiac output to simultaneously support metabolism and thermoregulation during exercise-heat stress. PMID- 1602939 TI - Carbohydrate and fluid ingestion during exercise: are there trade-offs? AB - Intense exercise (i.e.; above 60% VO2max) can be maintained for prolonged periods provided sufficient carbohydrate is available for energy and the heat generated from muscle metabolism does not cause excessive hyperthermia and/or dehydration due to sweating. It is clear that people should ingest carbohydrate during prolonged exercise (i.e.; longer than 1-2 h), which causes fatigue because of an inadequate supply of blood glucose and that fluids should also be ingested in an attempt to offset dehydration and reduce hyperthermia. Ingestion of approximately 30-60 g of carbohydrate (i.e.; glucose, sucrose, or starch) during each hour of exercise will generally be sufficient to maintain blood glucose oxidation late in exercise and delay fatigue. Since the average rates of gastric emptying and intestinal absorption can reach 1 l.h-1 for water and solutions containing up to 8% carbohydrate, exercising people can be supplemented with both carbohydrate and fluids at relatively high rates (over 60 g.h-1 of carbohydrate and 1 l.h-1 of fluid). Therefore, when sweat rate is not high (i.e.; less than 1 l.h-1), the addition of carbohydrate to fluids, and vice versa, does not prevent adequate supplementation of each, especially if large volumes are consumed to keep the stomach somewhat full and thus increase gastric emptying. Therefore, in most situations there are no trade-offs between fluid and carbohydrate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602940 TI - Guidelines for optimal replacement beverages for different athletic events. AB - During exercise, especially endurance exercise in the heat, vital body fluids and essential ions are lost in sweat, and the body may deplete its glycogen stores. Unless essential body fluids are restored, these conditions can produce hypovolemia, hypoglycemia, hyponatremia, hyperthermia, and dehydration. Performance may also be reduced. This paper briefly reviews pertinent aspects of gastric emptying and intestinal absorption and proposes the formulation of beverages for ingestion both pre-event and during exercise. For events lasting less than 1 h, 300-500 ml of a 6-10% CHO beverage is recommended pre-event (0-15 min), and cool (5-15 degrees C) water in a volume approximately half the subjects sweat rate is recommended during exercise. For events between 1-3 h long, 300-500 ml of water is recommended pre-event, and 800-1600 ml.h-1 of a 6-8% CHO solution with 10-20 mEq Na+ is recommended during exercise. For events longer than 3 h, 300-500 ml of water is recommended pre-event, and 500-1000 ml.h-1 of a 6-8% CHO beverage with 20-30 mEq Na+ is recommended during exercise. In recovery, a beverage containing 5-10% CHO with 30-40 mEq Na+ should be ingested to achieve euhydration. A minimum of 50 g.h-1 of CHO should be ingested in the first 2 h to maximize glycogen repletion. Guidelines to follow in formulating these beverages are reviewed and the rationale for each formulation is provided. PMID- 1602941 TI - Thermoregulatory responses of pre-, mid-, and late-pubertal boys to exercise in dry heat. AB - During exercise in a hot climate, children have been reported to have a less effective temperature regulation capability, compared with adults. It is likely that the transition from a child-like to an adult-like response occurs during puberty. To assess the association between the thermoregulatory response and physical maturation, three groups of circum-pubertal boys cycled at 50% VO2max (three 20-min bouts with 10-min rests), in a climatic chamber (42 degrees C, 20% relative humidity). Based on Tanner staging (pubic hair), 10 were classified as prepubertal (PP), 13 as midpubertal (MP), and eight as late pubertal (LP). Measurements included rectal and skin temperatures (Tre, Tsk), heart rate (HR), sweating rate (SR), oxygen consumption (VO2), and forearm blood flow (FBF). Tre, Tsk, and HR increased with time, with no significant difference among groups. Relative VO2 (ml O2.kg-1) was similar among groups. FBF was consistently higher in PP compared with LP. In spite of the higher SR (PP = 4.9 +/- 0.2, MP = 5.7 +/- 0.3, LP = 6.6 +/- 0.4 ml.min-1.m-2) (mean +/- SEM) among LP compared with PP, the rate of heat storage (PP = 5.5 +/- 0.4, MP = 5.3 +/- 0.4, LP = 6.8 +/- 0.3, kJ.h 1.kg-1) was also significantly higher among those in the LP group. Three of eight LP did not complete the session due to high Tre, while two of the 10 PP were unable to complete the session even though the physiologic heat strain was not high. The results suggest that the transition from a child-like to an adult-like thermoregulatory effectiveness in a hot, dry climate may occur at a somewhat later stage, but not during puberty. PMID- 1602942 TI - The movement of the heel within a running shoe. AB - Most running shoe investigations have used the same standard procedure for the evaluation of the shoes: the runners are filmed from behind and a film analysis is carried out digitizing markers at the heel counter of the shoe and on the lower leg. The angular displacement of these markers relative to the horizontal or the vertical is assumed to be an indicator for various sports injuries. The goal of this investigation was to measure the movement of the heel counter as well as the movement of the heel inside the shoe. First, the influence of the size of different heel counter windows was controlled and found negligible for the test conditions of this study. Second, 15 subjects performed the following procedure: running (a) barefoot, (b) with shoes with windows, and (c) without windows. Overall, the heel was found to move similarly but not identically to the heel counter. The maximum change of pronation was (a) 13.7 +/- 3.7 degrees, barefoot; (b) 14.1 +/- 3.8 degrees for the shoe with windows and 12.1 +/- 3.7 degrees for the heel inside these shoes; and 14.9 +/- 4.2 degrees for the shoes with no windows. To achieve a general impression of a shoe in the sense of a qualitative description, the previous method without heel counter windows still seems adequate. However, for a detailed analysis of quantitative nature, it is important to use the method with heel counter windows. PMID- 1602943 TI - Voluntary and electromyostimulation forces in trained and untrained men. AB - Electromyostimulation (EMS) evoked responses of lower extremity muscles of sedentary or disabled subjects have been extensively studied to improve muscular strength and delay atrophy. However, it is not apparent whether EMS can serve a similar function in upper extremity muscles and in athletes. We compared the forces of maximal voluntary isometric contraction (MVC), percutaneous EMS-evoked tetanus, and EMS superimposed on MVC of the elbow flexors in six strength-trained and six untrained healthy men. Stimulation consisted of a 2.5-kHz alternating current sine wave modulated at 50 bursts.s-1 with a 50% duty cycle. Reliability of the criterion measures was assessed over 4 d and ranged from R = 0.746 to R = 0.948. Strength-trained men had 29% higher MVC than untrained controls (P less than 0.001). Untrained men tolerated 21.9 mA and trained men 31.3 mA of EMS current (P less than 0.021), yet tetanic forces were similar: 92.5 N vs 96.0 N (P greater than 0.196). These tetanic forces corresponded to 32% (untrained) and 24% (trained) of MVC (P less than 0.047). When EMS was superimposed on MVC, compared with MVC alone, force was significantly (P less than 0.048) lower by 10% (31 N, untrained) and 13% (55 N, trained). These data suggest that, independent of training status, percutaneous EMS reduces maximal voluntary elbow flexion forces and that tetanic forces may not be sufficiently high for purposes of muscular strength development or prevention of atrophy. PMID- 1602944 TI - No effects of glycogen depleting exercise and altered diet composition on mood states. AB - To investigate the effects of glycogen depleting exercise and dietary composition on mood, 14 males completed the Profile of Mood States (POMS) questionnaire under four conditions. A control condition (CON) of ad libitum diet preceded any experimental manipulation. Subsequently, three treatments were administered randomly in a counterbalanced design: a) following a glycogen-depletion protocol and 3 d on a high-carbohydrate diet (93% of total caloric intake as carbohydrate [CHO]), b) following a glycogen-depletion protocol and 3 d on a low-CHO diet (23% of total caloric intake as CHO), and c) following 3 d of recorded ad libitum dietary consumption. Conditions a and b simulated phases of popular glycogen loading protocols, and condition c served as a second control condition confirmed by records of dietary intake. The POMS measured tension-anxiety, depression dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion bewilderment. A composite score of total mood disturbance (TMD) was computed by summing the subscale scores (weighting vigor-activity negatively). Dietary composition (fat, protein, and CHO content) differed significantly (P less than 0.001) among the three treatments, but total caloric intake was not different. No significant differences were found among the treatment and control conditions for TMD or any POMS subscale score. We find no evidence that the 3-d glycogen loading protocol we employed with healthy, moderately fit, young males can be expected to confound performance measures by altering mood. PMID- 1602945 TI - Psychobiologic responses to exercise at different times of day. AB - The primary purpose of this investigation was to determine whether selected psychobiologic responses to running exercise vary as a function of the time of day at which exercise is performed. Twelve adult males completed four bouts of randomly assigned, submaximal exercise (20-min runs at 70% VO2max) at 0800, 1200, 1600 and 2000 h. Since selected personality traits have previously been shown to influence circadian rhythms, personality assessments (i.e., Eysenck Personality Questionnaire, EPQ; Morningness-Eveningness Questionnaire, MEQ; Spielberger's State-Trait Anger Expression Inventory, STAIX; and State-Trait Anxiety Inventory, STAI) were made during the initial testing session. The group studied scored within the normal range on the traits assessed by the EPQ, STAIX, and STAI. Also, subjects were not able to be classified as either "morning" or "evening" types based on MEQ scores. Ten minutes before as well as 10 and 20 min following the exercise bouts, state anxiety, state anger, blood pressure, and heart rate were assessed. Multivariate ANOVAs (four time of day conditions x three trials) revealed significant main effects for the trial factor for state anxiety, state anger, heart rate, and systolic blood pressure. State anxiety, state anger, and systolic blood pressure were found to be reduced at both the 10 and 20 min post exercise assessment periods when compared with pre-exercise levels. ANOVAs performed on the difference scores showed that the mood improvements and cardiovascular changes were independent of the time of day that exercise was performed, and these findings were confirmed by ANCOVAs, which adjusted for differences in initial values across the four time of day conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602946 TI - Effect of oxygen breathing following submaximal and maximal exercise on recovery and performance. AB - To determine whether supplemental oxygen following exercise hastens recovery or enhances subsequent performance we evaluated its effectiveness in 13 male athletes. The exercise periods consisted of two 5-min submaximal efforts on a treadmill ergometer followed by a single bout to exhaustion. Intervals of exercise were separated by a 4-min recovery period during which the subject breathed either 1) room air, 2) 100% oxygen, or 3) 2 min of 100% oxygen followed by 2 min of room air on three nonconsecutive days. We found that breathing 100% oxygen produced no significant difference on the recovery kinetics of minute ventilation or heart rate, or improvement in subsequent performance as measured by duration of exercise (3.33 +/- 0.04 min, air vs 3.46 +/- 0.03, oxygen) and peak VO2 (59.9 +/- 2.2 ml.kg-1.min-1, air vs 54.5 +/- 2.2, oxygen). In addition, the perceived magnitude of exertion estimated by the Borg scale was no different during oxygen breathing. These findings offer no support for the use of supplemental oxygen in athletic events requiring short intervals of submaximal or maximal exertion. PMID- 1602947 TI - Chronic multivitamin-mineral supplementation does not enhance physical performance. AB - The effects on physical performance of 90 d of supplementation with a high potency multivitamin-mineral supplement were studied in a double-blind, placebo controlled design. Twenty-two healthy, physically active men were randomly assigned to a supplement (S) or placebo (P) group; both groups had similar physical characteristics. Performance was assessed from maximal aerobic capacity, endurance capacity, and isokinetic tests. Supplementation did not affect maximal aerobic capacity: pre and after approximately 12 wk of supplementation values for maximal oxygen consumption (48.5 +/- 1.3 vs 46.2 +/- 1.1 ml.kg-1.min-1), maximal heart rate (186 +/- 2 vs 187 +/- 2 beats.min-1) or treadmill time (19.96 +/- 0.48 vs 19.99 +/- 0.37 min) did not differ in the S group; similar findings were noted in the P group. Performance during the 90-min endurance run, as assessed from heart rates, rectal temperatures, and plasma glucose, lactate and adrenocorticotropin values, was not affected by treatment. Similarly, muscle strength and endurance were not affected. Thus, supplementation did not affect physical performance in well-nourished men who maintained their physical activity. PMID- 1602948 TI - Attenuation of contraction-induced skeletal muscle injury by bromelain. PMID- 1602949 TI - [Thyroid epitheliomas in French Polynesia]. AB - The authors reviewed 34 cases of thyroid epithelioma registered in French Polynesia from 1985 to 1990. Annual incidence classifies French Polynesia as a region with low endemicity. The patients were 31 females and 3 males. In 18 cases, carcinoma was discovered within a multiheteronodular goitre (MHNG) and in 16 cases within an isolated nodule. In each of these sub-groups, 4 micropapilliform cancers discovered at the occasion of a histopathological test. The mean age of the patients carrying a noduliferous cancer is 36.5 years and the one of multiheteronodular goitre is 50. No particular risk factor was discovered. Mean age of the disease is 2.8 years as far as noduliferous cancers are concerned, and 8.5 years for multiheteronodular goitre. The anatomical and echographic characters are discussed. What demanded a surgery intervention is reviewed. Mortality during intervention is zero. Morbidity recorded 17% of unilateral recurrent paralysis and 50% of transitory parathyroid insufficiency. Extemporaneous anatomopathological test was contributing in 25% of the cases; definitive test revealed 25 (74%) papilliform cancers (of which 8 micropapilliforms) and 9 vesicular cancers (26%). No canceration anaplasia was discovered. Evolutive stage is precised: 7 local invasions (isthm and/or capsule), 4 bifocal localizations, 8 cancers with adenoid metastasis, 4 with osseous and/or pulmonary metastasis. The way to select a therapy is reported and discussed. Cost evaluation is suggested in order to discuss the possibility to acquire for the Territory an equipment for isotopic exams. PMID- 1602950 TI - [Leptospirosis in French Polynesia: 120 case reports]. AB - Because of its clinical polymorphism and the difficulties to made a bacteriological and/or serological diagnosis, leptospirosis is an affection always non-detected. Nevertheless it is daily met affection in French Polynesia. Based on a homogenous series of 120 observations gathered from 1984 to 1990, all of them bacteriologically and/or serologically confirmed, we studied the different clinical and evolutive features of that disease. Fever is present in 91.6 p.c., cephalgia in 79.16 p.c. and myalgia in 70.83 p.c. Admission was necessary once out of four times. The four syndromes we observed in Tahiti are: infections syndrome, meningeal syndrome (30 p.c.) associated to an hyperproteinic grade in the C.S.F. (40 p.c.) and a lymphocytic reaction (60 p.c.). Liver syndrome, with hepatalgia (58.33 p.c.) and pain at the mass motion of liver (65 p.c.), that is an important sign in the local context; jaundice (28.33 p.c.) on the presence of which we must not based a diagnosis of leptospirosis: Biological renal syndrome displayed by transitory renal insufficiency with proteinuria, hematuria and leucocyturia. Neurological complications are mainly of encephalitic manifestations (5.8 p.c.). Hemorrhagic syndrome is expressed in digestive hemorrhage (8.33 p.c.) epistaxis (6.66 p.c.) and hemoptysis (6.66 p.c.). Cardiovascular manifestations are expressed in collapsus in 5.83 of the cases. Pulmonary abnormalities are frequent: cough (26.66 p.c.) and non specific X Ray image (19.16 p.c.). All patients are treated by Penicillin G (10 to 20 millions per day) by parenteral route with enteral alternative for an average of 10 days. Recovery was fast (7 to 10 days). In 65.8 p.c., slower in 15 p.c. (15 to 20 days); failure at first stage was observed in 10 p.c. of the cases, and relapse at medium or long term occurred under treatment in 8 cases (6.66 p.c.). Three dead were deplored (mortality 2.5 p.c.). PMID- 1602951 TI - [Hepatic amebiasis in French Polynesia. Study of 42 cases ]. AB - The authors aimed at describing and analysing retrospectively the clinical, serological, anatomical and evolutive aspects of 42 cases of hepatic amoebiasis treated and followed up in Papeete (French Polynesia) from 1984 to 1990. Painful hepatomegalia with fever, was a revealing sign once out of two. Complications started at initial stage only twice. Amoebic serology (by immunofluorescence or hemagglutination) was always positive, while pathogenic amoeba was absent in 95.2 p.c. of the cases. Hepatic amoebiasis always produces an intra-hepatic collection of pus: to that point of view, superiority of echotomography on other methods of investigation is evident, particularly to diagnose multiple collections (45.25 p.c. in this series). Recovery was always got, in most of the cases by only a medical treatment (39 cases) or in association with a puncture (2 cases). Nitro imidazol compounds are the preferred treatment. They were efficient in all cases but one, and were always followed by a systematic colic parasiticidal treatment with a contact amoebicide. PMID- 1602952 TI - [The non-insulin-dependent diabetic (type II) in Tahiti]. AB - The authors report on the monitoring in the Diabetology Service of the Territorial Hospital Center of Papeete (French Polynesia) of 51 Polynesians, diabetics non insulin-dependent over periods of 12 to 30 months (average 26.5 months) from July 1988 to December 1991. 31 males and 20 females (sex-ratio 1.5). Mean age: 55.9 (extremes: 22 and 76 old years). Non insulin-dependent diabetes risk factors: heredity (43%), obesity (67%), new-born babies with a weight more than 4 kg (10%). Revealing factors of diabetes: systematic check-up (37%), clinical complications (36%), cardinal signs (20%). Recorded complications are: 1. microangiopathy: nephropathy (25%) including 7 renal insufficiency and 2 patients under dialysis; retinopathy (29%); 2. macroangiopathy: cardiovascular accident 1 case; angor 4 cases; obliterative arteritis of inferior limbs 5 cases; 3. neuropathy 9 cases (17%); 4. high arterial tension 55%; 5. metabolic complications (20%): 4 acidocetosis; 2 hyperosmolar coma; 4 severe hypoglycemia; 6. 16 diabetic feet (32%) among them 8 amputations; 7. 45 infectious complications in 27 patients are reviewed. Review of the complications according to diseases ancientness; before 10 years of evolution, each patient suffered of at least one complication, after 10 years, each patient got an average of 2 complications. Review of diabetic balance: 80% of the patients present a mean glycemia greater than 1.50; 54% present a postprandial glycemia greater than 2 gr. and 34% a A1 C Hb greater than 9%. The possible treatments are reviewed. During this monitoring, mortality was one case; 35 patients were admitted totaling 881 days of hospitalization. PMID- 1602953 TI - [Cerebral vascular accidents in French Polynesia]. AB - The authors report on the results of a survey on cardiovascular accidents hospitalized between 01 April 1990 and 31 January 1991 carried out in the Services of Medicine and Cardiology in the Territorial Hospital Center of Papeete. This survey was: 56 cardiovascular accidents: 1/4 (hemorrhagic and 3/4 (42) ischemic. Mean age 59 (extremes 23-86). 36 males (64%); 20 females (36%). 50 Polynesians; 6 Chinese people. Among the risk factors recorded, 38 (68%) were hypertensed patients; 17 (30%) were due to tabagism and 15 (25%) to diabetes; 3 (5%) are known to be carriers of a hypercholesterolemia. 59% of the patients had no case history; 25% the cardiovascular accidents have been observed in patients with cardiopathy; 12.5% are recurrent cardiovascular accidents. Clinically, 5 transient ischemic accidents (12%) out of 42 cardiovascular ischemic accidents. High arterial tension was recognized in 12/14 (86%) of hemorrhagic cardiovascular accidents and in 26/42 (62%) of ischemic cardiovascular accidents. In 42 ischemic cardiovascular accidents, 31 patients suffered from cardiopathy (74%) of which 15 (36%) presented an embolic cardiopathy. Interest of echography and electrocardiogram are discussed. Ultrasonic exam of carotid vessels was found abnormal in almost half of the cases when utilized (12/26). Finally, etiological diagnosis was certain in 17 cases, of presumption in 16 cases, and in 9 cases, it was not possible to precise any cardiovascular etiology. Tomodensitometric tests are discussed. 86% of the ischemic cardiovascular accident were treated with anticoagulants/thrombocyte antiagglutination. 24% of the patients died, 50% recovered incompletely and 26% completely. PMID- 1602954 TI - [Goiter in Tahiti]. AB - The authors report on a prospective study about goitre in French Polynesia carried out in 1989, dealing with epidemiology and disease characterization in 39 patients. 1. Epidemiology of goitre in Tahiti; In schools: 517 children (236 boys and 281 girls) aged from 10 to 15. Prevalence rate is 1.55 p.c. (8/517); Adults: 226 adults (112 males and 114 females) aged from 50 to 65. Prevalence rate is 4.42 p.c. (10/226). 2. Case study on 39 Polynesian patients (38 females and 1 male) living in Tahiti (mean age: 35.6 years old) showing euthyroidic goitre, detected from 1989 April 1st and October 31; Goitre did not present in Tahiti any particularity. It is a pathology mainly feminine, at low evolution and late local consequences; In 3/4 of the cases, goitre is visible and more it is voluminous more modules are present; There is no iodine deficiency, and the mean value of iodine excretion (536 mcg/24 h) is very high in comparison with what is described in the literature; Presence of a high thiocyanatemia (greater than 100 mmol/l) is found in 1/4 of the patients; There is no correlation between consumption of foods well-known as cyanogenical ones and the level of thiocyanatemia; There is a correlation between the rate of thiocyanatemia and tabagism. PMID- 1602955 TI - [Study of hyperuricemia in Tahiti. 31 cases hospitalized at the Territorial Hospital Center in Papeete (Tahiti)]. AB - Frequency of gout in French Polynesia has induced us to define a type of "hyperuricemia Polynesian" from a population of patients admitted in a general Medicine Ward. Each admitted patient gets immediately a blood check-up. A figure higher than 70 mg/l in male and 60 mg/l in female is considered as pathological. In such a case, uricemia and uraturia are tested every 24 h for three days and we consider the mean value of these three tests. On the other side, some admitted patients non-hyperuricemic, are examined according to the same protocol. So, we have two groups: 31 hyperuricemics and 20 non-hyperuricemics, secondarily grouped according to age, sex, ethnic. We did not consider some secondary causes of hyperuricemia (chronic renal insufficiency diuretic treatment, psoriasis etc.). 1. Within the hyperuricemic population, mean uricemia is 85.35 mg/l versus 52.65 mg/l in the second sample. In the hyperuricemic group (21 males and 10 females) 48% are gouty and 13% of them are females. Articular manifestations are acute arthritis, affecting mainly inferior limbs, ankles, knees). We did not notice any significant divergence between uricemia and uraturia of gouty and non gouty people. Within the group of gouty people, percentage of individual hyper excretion is 53% (uraturia greater than 600 mg/24 h) with no significant divergence with the non-gouty group: Nephrolithiasis is rare (3%). There is no significant divergence between urinary pH of gouty and non-gouty people. Associated metabolic troubles are: diabetes (26%) high triglyceridemia (43%) three syndromes associated together (hyperuricemia + diabetes + hypertriglyceridemia) in 19.5%, total cholesterol is normal (2.07 g/l) but a low cholesterol (0.30 g/l).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602957 TI - [Upper femoral epiphysiolysis in French Polynesia. Hip pain with serious consequences]. AB - High femoral epiphysiolysis is a frequent disability in French Polynesia, occurring more in obese young people that being a morphotype quite frequent in this geographical area. It is often at the stage of acute epiphysiolysis or fixed coxa vara these patients are examined. At such stage, sequellae are major and evolving to precocious coxarthrosis. It is at a stage of progressive coxarthrosis at the beginning that treatment and recovery are possible without sequellae. Any practitioner has to think about it when confronted to any pain in a hip of teenager, so a surgical treatment, in good conditions could be performed. PMID- 1602956 TI - [Evaluation of the efficacy of mannitol in the treatment of ciguatera in French Polynesia]. AB - Up till now, in the French Polynesia and in New Caledonia, people showing ciguatera intoxication receive a standard treatment: calcium + vitamins B6 and C by intravenous way and in addition, some drugs arriving to cure some symptomatic manifestations. In 1988, an investigation carried out in Majuro, Marshall Islands concluded that intravenous mannitol is efficient in the treatment of serious intoxications with suspecting cerebral oedema. Since, such a treatment has been utilized with success in several endemic areas. Our therapeutic evaluation was arrived to determine whether mannitol's efficiency is higher than the standard treatment in the ciguatera intoxications of mean seriousness. This investigation was carried out on two randomized groups: The first one receiving mannitol (250 cc intravenous at 20% injected in 1 h) the second one receiving the standard treatment (intravenous perfusion glucose serum 250 cc with 1 g of vitamins C, 250 mg of vitamin B6 and 1 g of calcium gluconate injected in 1 h). Seriousness of clinical status was evaluated according to a scale of score from 0 to 50, based on the importance of the clinical manifestations paresthesia, aches, asthenia, cardiovascular and digestive signs. Only patients getting a score at least 20 were included in this investigation. Clinical status of each patient was evaluated before any treatment (initial score) at the end of perfusion and at the 24th hour. Efficiency of each treatment respectively was evaluated according to the differences between these three different scores. CHI 2 and U Mann's and Whitney's tests were utilized for the statistical analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602958 TI - [Liver abscess. Imaging and interventional radiology in French Polynesia]. AB - 23 cases of liver abscess are reported (13 pyogenous, 10 amoebic). Clinical feature is rather uniform and evocative; thanks to picture technics, diagnosis was easy in 22 cases but hesitating in one case. Semeiology revealed by scanner or echography is detailed. Both techniques are fairly equivalent considering accuracy but not really specific. The interventional radiology at the stage of diagnosis, consists in puncture (14 out of 23 cases), at the stage of therapy, in transcutaneous drainage (6/23 cases). They are performed with the assistance of scanner, echoscopy and/or radioscopy. Therapy has been medical in 13 cases/23, associated with transcutaneous drainage 6 times, surgical in 4 cases. A procedure is proposed, including early puncture to diagnose, drainage of pyogenous abscesses, only medical treatment against amoebiasis exceptionally help of surgery and controlled by echography. PMID- 1602959 TI - [French polynesia]. PMID- 1602960 TI - [Psychological follow-up of 52 patients in an internal medicine service at the Territorial Hospital Center of Papeete (Tahiti)]. AB - This prospective study of a duration of 7 months was made on 52 patients admitted in a International Medicine Service and watched over psychological aspect. The sample was composed mainly of Polynesians, two third of them being females. On the somatic aspect, the complaint more frequently recorded is a painful condition. Diagnosis of depressive status is made about almost half of the patients. The most obvious point is that Polynesian depressive patients are young and they expressed their profound discomfort not only by a suicidal attitude but also by a symptomatology in which body, body surface are the privileged significants. PMID- 1602961 TI - What is known about the structure and function of the Escherichia coli protein FirA? AB - The firA gene is essential for growth of Escherichia coli growth and lies in the 4-minute region of the genome. firA encodes the FirA protein which contains 341 amino acids and has an apparent molecular mass of 36 kDa. Genetic evidence suggests that FirA plays a role in transcription since certain firA alleles confer temperature sensitivity for growth and RNA synthesis as well as reversing the rifampin resistance of rifampin-resistant rpoB mutants ('fir' effect). FirA co-immunoprecipitates with RNA polymerase holoenzyme, implying a physical association with the transcriptional machinery, possibly with the beta subunit of RNA polymerase. FirA contains a previously undescribed isoleucine/valine-rich six amino-acid repeat occurring 14 times within the N-terminal and 12 more times within the C-terminal half of the protein. This repeat can be formulated as [HXXXhZ]n with 'H' representing a large non-polar residue (usually isoleucine), 'h' representing a smaller non-polar residue, 'Z' representing either charged/polar or aromatic residues, XXX representing residues typical of beta turns, and 'n' being equal to the repeat number. We refer to this repeat as an isoleucine patch. Proteins encoded by three E. coli acyltransferases also contain this motif which is roughly positioned in each case, within the amino- and carboxyl termini, as in FirA. When the sequences of these proteins are aligned, a region of poor similarity separates the isoleucine patches. The significance of these repeats remains unknown although we speculate that they play an important structural role in the organization and function of FirA (and other proteins containing isoleucine patches), possibly by acting as homo- or hetero dimerization interfaces.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602962 TI - The suicidal DNA repair methyltransferases of microbes. AB - Virtually every organism so far tested has been found to possess an extremely efficient DNA repair mechanism to ensure that certain alkylated oxygens do not accumulate in the genome. The repair is executed by DNA methyltransferases (MTases) which repair DNA O6-methylguanine (O6MeG), O4-methylthymine (O4MeT) and methylphosphotriesters (MePT). The mechanism is rather extravagant because an entire protein molecule is expended for the repair of just one, or sometimes two, O-alkyl DNA adduct(s). Cells profit from such an expensive transaction by earning protection against death and mutation by alkylating agents. This review considers the structure, function and biological roles of a number of well-characterized microbial DNA repair MTases. PMID- 1602963 TI - Phosphorylation of IcsA by cAMP-dependent protein kinase and its effect on intracellular spread of Shigella flexneri. AB - Shigella flexneri, a Gram-negative bacillus belonging to the family Enterobacteriaceae, causes bacillary dysentery in humans by invading colonic epithelial cells. Processes by which epithelial cells, which are not professional phagocytes, may limit the spread of the invading microorganisms are poorly understood. This paper shows that IcsA (VirG), a 120 kDa bacterial outer membrane protein responsible for intracellular and cell-to-cell spread through polymerization of actin, is a major substrate for phosphorylation by cyclic dependent protein kinases. Site-directed mutagenesis of a sequence encoding phosphorylation consensus motif SSRRASS, located at residues 754-760, almost completely abolished the ability of this protein to be phosphorylated by protein kinase A. Such mutants expressed a 'super lcs' phenotype, characterized by an increased capacity to spread from cell-to-cell during the first three hours of infection in the HeLa cell infection assay. These data suggest that host-cell phosphorylation of key virulence proteins located on the bacterial surface may represent a significant host defence mechanism during the invasion process. PMID- 1602964 TI - Rhizobium leguminosarum has two glucosamine synthases, GlmS and NodM, required for nodulation and development of nitrogen-fixing nodules. AB - The Rhizobium leguminosarum nodM gene product shows strong homology to the Escherichia coli glmS gene product that catalyses the formation of glucosamine 6 P from fructose 6-P and glutamine. DNA hybridization with nodM indicated that, in addition to nodM on the symbiotic plasmid, another homologous gene was present elsewhere in the R. leguminosarum genome. A glucosamine-requiring mutant was isolated and its auxotrophy could be corrected by two different genetic loci. It could grow without glucosamine when the nodM gene on the symbiotic plasmid was induced or if the cloned nodM gene was expressed from a vector promoter. Alternatively, it could be complemented by a second fragment of R. leguminosarum DNA that carries a region homologous to E. coli glmS. Biochemical assays of glucosamine 6-P formation confirmed that the two R. leguminosarum genes nodM and glmS have interchangeable functions. No nodulation of peas or vetch was observed with a double nodM glmS mutant, and this block occurred at a very early stage since no root-hair deformation or infection threads were seen. Nodulation and root-hair deformation did occur with either the nodM or the glmS mutant, showing that the gene products of either of these genes can be involved in the formation of the lipo-oligosaccharide nodulation signal. However, the glmS mutant formed nodules that had greatly reduced nitrogen fixation. Constitutive expression of nodM restored nitrogen fixation to the glmS mutant. Therefore the reduced nitrogen fixation probably occurs because glmS is absent and nodM is not normally expressed in nodules and, in the absence of glucosamine precursors, normal bacteroid maturation is blocked. PMID- 1602965 TI - Molecular basis of host epithelial cell recognition by Trichomonas vaginalis. AB - Parasitism of host epithelial cells by Trichomonas vaginalis is a highly specific event. Four trichomonad surface proteins (adhesins) with molecular masses of 65,000 daltons (65 kDa; AP65), 51 kDa (AP51), 33 kDa (AP33), and 23 kDa (AP23) mediate the interaction of T. vaginalis with epithelial cells. Fresh isolates, when compared with long-term-grown isolates, had greater amounts of adhesins, which corresponded with increased levels of cytoadherence. Anti-adhesin antibodies reacted by immunoblot only with the respective protein and detected, by indirect immunofluorescence, each adhesion on the parasite surface. These antibodies inhibited the binding of live parasites to epithelial cells and protected epithelial cells from contact-dependent cytotoxicity. The pretreatment of epithelial cells with a preparation of purified adhesions also blocked trichomonal cytoadherence. Moreover, HeLa cells possessed molecules which recognized and bound to adhesins on nitrocellulose blots. PMID- 1602966 TI - Osmoprotectants and phosphate regulate expression of phospholipase C in Pseudomonas aeruginosa. AB - Phospholipase C has been increasingly recognized as a significant virulence determinant in the pathogenesis of Gram-negative and Gram-positive infections. Pseudomonas aeruginosa carries two, non-tandem genes encoding phospholipase C (PLC) activity. One PLC (PLC-H) haemolyses human and sheep erythrocytes while the other is not haemolytic for these kinds of red blood cells. It was previously determined that the synthesis of both PLCs is regulated by inorganic phosphate (Pi), but little else was known regarding the regulation of these potentially important virulence determinants of P. aeruginosa. In this report, data are presented demonstrating that both PLC genes are regulated at the transcriptional level by Pi and by a P. aeruginosa homologue of the positive regulator of genes in the Pi regulon of Escherichia coli, i.e. PhoB. In addition to Pi, it is also shown in this report that the synthesis of both PLC-H and PLC-N is induced by compounds which are not only derived from the substrate product of both enzymes, i.e. phosphorylcholine, but are also known osmoprotectants in eukaryotic and prokaryotic cells. The osmoprotective derivatives of phosphorylcholine which induce the synthesis of PLC in P. aeruginosa include choline, glycine betaine, and dimethylglycine, but not sarcosine (monomethylglycine) or glycine. By constructing mutants which are deficient in the production of each separate PLC and in the production of PhoB it was determined that induction of PLC-H by the osmoprotective compounds is independent of Pi concentration and PhoB, while induction of PLC-N by these compounds requires Pi-deficient conditions and PhoB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602967 TI - Cloning, sequencing and distribution of the Salmonella typhimurium LT2 sialidase gene, nanH, provides evidence for interspecies gene transfer. AB - The Salmonella typhimurium LT2 sialidase (neuraminidase, EC 3.2.1.18) structural gene, nanH, has been cloned and sialidase overproduced from multicopy plasmids in Escherichia coli. Sialidase expression was regulated positively by cAMP. In contrast, certain Tn1000 insertions located upstream of nanH coding sequences reduced sialidase activity. A nanH chromosomal insertion mutation constructed by marker exchange demonstrated a single sialidase gene copy in S. typhimurium LT2. The complete nucleotide sequence of nanH, encoding a 41,300 dalton polypeptide, was determined and the derived primary structure was similar to sialidases from Clostridium perfringens, Clostridium sordellii, Bacteroides fragilis, and Trypanosoma cruzi. Comparative sequence analysis, including codon usage and secondary structure predictions, indicated that the S. typhimurium and clostridial sialidases are homologous, strongly suggestive of an interspecies gene transfer event. At least two primary sequence motifs of the bacterial enzymes were detected in influenza A virus sialidases. The predicted secondary structure of the bacterial enzymes was strikingly similar to viral sialidase. From the population distribution of nanH detected within a collection of salmonellae, it was apparent that S. typhimurium obtained its nanH copy most recently from Salmonella arizonae. S. typhimurium LT2 is thus a genetic mosaic that differs from other strains of even the same serotype by nanH plus potentially additional characters linked to nanH. These results have relevance to the evolution and function of sialidases in pathogenic microbes, and to the origin of the sialic acids. PMID- 1602968 TI - Analysis of an Escherichia coli mutant strain resistant to the cell-killing function encoded by the gef gene family. AB - The chromosomal genes gef and relF from Escherichia coli and the plasmid-encoded genes hok, flmA, srnB, and pndA constitute the gef gene family, which encodes a cell-killing function. In order to investigate the mechanism of cell killing we have isolated an E. coli mutant strain that is resistant to the overexpression of the toxic proteins encoded by the gef gene family. This phenotype requires at least two mutations, one of which has been mapped to 55.2 minutes. This mutation was sequenced and shown to represent a single base substitution in an open reading frame (ORF178) encoding a putative membrane protein having a molecular mass of 20.1 kDa. ORF178 and an upstream frame, ORF190, probably constitute an operon. PMID- 1602969 TI - The D1 protein of the photosystem II reaction-centre complex accumulates in the absence of D2: analysis of a mutant of the cyanobacterium Synechocystis sp. PCC 6803 lacking cytochrome b559. AB - The reaction center core of photosystem II, a multiprotein membrane bound complex, is composed of a heterodimer of two proteins, D1 and D2. A random mutagenesis technique was used to isolate a photosystem II deficient mutant, CP6t16, of the unicellular cyanobacterium, Synechocystis sp. PCC 6803. Nucleotide sequence analysis showed that the primary lesion in CP6t16 is an ochre mutation introducing a translational stop codon in the psbE gene, encoding the alpha subunit of cytochrome b559, an integral component of the PSII complex. Analysis of the protein composition of CP6t16 thylakoid membranes isolated in the presence of serine protease inhibitors revealed that, in the absence of cytochrome b559, the D2 protein is also absent. However, the D1 protein is stably incorporated in these membranes, suggesting that the synthesis and integration of D1 are independent of those of D2 and cytochrome b559. PMID- 1602970 TI - Alternatives to Aroclor 1254-induced S9 in in vitro genotoxicity assays. AB - A working party was set up by the UK Environmental Mutagen Society to consider alternatives to Aroclor 1254 (Aroclor)-induced S9 in in vitro genotoxicity assays, with the aims of considering whether a replacement for Aroclor in its role in general screening assays could be readily identified. The working party concluded that there was sufficient support in the literature to justify the use of an appropriate phenobarbital/beta-naphthoflavone regime as an acceptable alternative to Aroclor. PMID- 1602971 TI - Development of assays for the detection of photomutagenicity of chemicals during exposure to UV light. II. Results of testing three sunscreen ingredients. AB - Three sunscreen ingredients, derivatives of benzylidene camphor, were tested for photomutagenic potential. These were benzenesulfonic acid, 4-[(4,7,7,-trimethyl-3 oxo-bicyclo [2.2.1] hept-2-ylidene) methyl] (Mexoryl SL), 4-(2-oxo 3 bornylidenemethyl) phenyl trimethylammonium methyl sulphate (Mexoryl SO) and 3,3' (1,4-phenylenedimethylidyne) bis [7,7-dimethyl-2-oxo-bicyclo [2.2.1] heptane-1 methanesulfonic acid] (Mexoryl SX). Two complementary assay systems were used, one involving the induction of reverse mutations in Escherichia coli strain WP2, the other measuring the induction of chromosome damage in Chinese hamster ovary (CHO) cells. Irradiation with UVA and/or UVB was provided by an Osram Ultra Vitalux sunlamp. None of the three sunscreens, tested either to the limit of solubility or toxicity, gave any indication of photomutagenicity in either assay, under conditions in which the positive control compound, 8-methoxypsoralen, was extremely photomutagenic. It is concluded that Mexoryls SL, SO and SX can be exposed to UV light without producing photomutagenicity measurable using a bacterial reverse mutation or a mammalian chromosome aberration assay. PMID- 1602972 TI - Differences in genotoxic activity of alpha-Ni3S2 on human lymphocytes from nickel hypersensitized and nickel-unsensitized donors. AB - The genotoxic activity of alpha-Ni3S2 was assessed on human lymphocytes from nickel-hypersensitized (SSL) and nickel-unsensitized (USL) subjects. Three genotoxicity tests were performed: the sister chromatid exchange (SCE) test, the metaphase analysis test and the micronucleus test. (i) The SCE test (3-100 micrograms/ml) showed a weak but statistically significant increase in the number of SCE in both lymphocyte types with respect to controls, USL presenting a slightly higher SCE incidence but only at one concentration. (ii) The metaphase analysis test demonstrated a high dose-dependent clastogenic activity of alpha Ni3S2 in both lymphocyte types. The frequency of chromosomal anomalies was significantly higher in USL than in SSL for all concentrations applied. (iii) The micronucleus test confirmed the dose-dependent clastogenic activity of alpha Ni3S2 and the differences already observed between USL and SSL, i.e. the number of cells with micronuclei was statistically higher in USL. Finally, the incorporation study with alpha-63Ni3S2 showed a higher uptake of its solubilized fraction by USL. This allows an explanation of the different genotoxic action of nickel on the two cell types. In this study we demonstrated that hypersensitivity has an influence on the incorporation of alpha-Ni3S2 and subsequently on the different induction of chromosomal aberrations in human lymphocytes. PMID- 1602973 TI - Micronucleus induction by camptothecin and amsacrine in bone marrow of male and female CD-1 mice. AB - Camptothecin (CPT) and amsacrine (m-AMSA), specific inhibitors of topoisomerase I and II, were tested for micronucleus inducing potential in bone marrow of male and female CD-1 mice. CPT was given as intraperitoneal (i.p.) injections at 0 h in doses of 1, 2 and 4 mg/kg, and at 0 + 24 h in doses of 0.5, 1 and 2 mg/kg. Bone marrow samples were taken 30 and 48 h post 0 h dosing in both the single and split dose studies. The same i.p. regimens were used to evaluate m-AMSA at doses of 1.5, 3 and 6 in the single, and 0.75, 1.5 and 3 mg/kg in the split dose study. Both compounds were tested in two consecutive experiments using identical study designs to confirm findings or trends. The CPT experiment showed that more micronuclei (MN) were induced at 30 h than at 48 h following both 0 h and 0 + 24 h treatment, and that dose interaction occurred as two divided doses of CPT induced as much or more micronuclei than the same total single dose in both sexes. No overall sex differences were found in the 0 h dose study at 30 or 48 h. However, females had significantly more MN than males at 30 h following 0 + 24 h dosing, indicating an inducible female G2 mitotic effect in proliferating bone marrow blast cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1602974 TI - Identification of kinetochore-containing (CREST+) micronuclei in mouse bone marrow erythrocytes. AB - A methodology for the characterization of kinetochore-containing (CREST+) micronuclei (MN), based on the use of antikinetochore antibodies (derived from CREST patients) and indirect immunofluorescence, was applied to mouse bone marrow erythrocytes. The proposed protocol allows us to obtain fluorescent signals of good quality and highly reproducible data. The clastogenic agent mitomycin C (MMC; 1 mg/kg body wt) and the two aneugenic compounds chloral hydrate (CH; 200 mg/kg body wt) and colchicine (COL; 1 mg/kg body wt) were used to verify the sensitivity of this approach to chemicals with different mechanisms of action. These compounds were tested at a 20 h time interval from treatment and all of them were able to significantly increase (P less than 0.001) the frequency of MN in polychromatic erythrocytes. Of the MN observed in preparations from control animals, 45% were CREST+ and this percentage increased significantly (P less than 0.001) after treatment with CH or COL. On the contrary, only 22% CREST+ MN were found after treatment with MMC (statistical comparison with the control value: P less than 0.001). The CREST characterization of MN induced in vivo in mouse bone marrow allows us to infer the origin of MN formation, thus contributing to the identification of aneugenic agents. PMID- 1602975 TI - Skin carcinomas and micronucleus induction in epidermal keratinocytes following 12-O-tetradecanoylphorbol-13-acetate and mezerein treatment. AB - Phorbol esters are chemical compounds which have the ability to promote carcinogenesis in the skin of mice. In the HRA/Skh mouse strain, an initiation promotion assay substantiated evidence that mezerein acts as a complete promoter. Complete promotion with 9.0 nmol mezerein induced a total of 53 papillomas in 28 mice within 40 weeks, while 1.5 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA), using the same application regime, resulted in a total of 298 papillomas in 58 mice. However, 7.6% of the papillomas in the mezerein group progressed to carcinomas, compared with 0.7% in the TPA group. Approximately the same molar concentrations of TPA and mezerein induced a dose-dependent and reproducible increase in micronuclei in supra-basal cells derived from the epidermis of treated mice. In contrast, the latter compound was less toxic to these cells and induced higher numbers of micronuclei at the higher concentrations. PMID- 1602976 TI - Morphological transformation of an established Syrian hamster dermal cell with the anti-tussive agent noscapine. AB - Following exposure to the alkaloid noscapine hydrochloride over a concentration range of 10-120 micrograms/ml immortal cultures of Syrian hamster dermal fibroblasts were shown to undergo morphological transformation. The resultant transformed foci produced cultures which were anchorage independent as confirmed by soft agar tests. Karyotype analysis of a noscapine transformed colony demonstrated an increase in chromosome number compared to the immortal culture and the non-random duplication of a translocated chromosome 9 previously identified in the immortal culture. These data indicate that noscapine, which has previously been shown to be a spindle inhibitor and inducer of polyploidy in cultured cells, is capable of inducing in vitro cell transformation. Such data indicate a carcinogenic potential for this widely used cough suppressant. PMID- 1602977 TI - Structural basis of the genotoxicity of polycyclic aromatic hydrocarbons. AB - The Computer Automated Structure Evaluation (CASE) system has been applied to investigate the structural basis of the genotoxicity of 37 polycyclic aromatic hydrocarbons examined with the Escherichia coli PQ37 genotoxicity assay (SOS chromotest). CASE identified eight activating and one inactivating structural fragments responsible, for the probability and three activating and one inactivating fragment responsible for the potency of the activity (P less than or equal to 0.15). The present analysis indicate that the main activating fragments identified by CASE were similar to the descriptor for the bay (or modified bay) and K region of PAHs. Using these fragments the computer correctly predicted the probability of genotoxicity of 93.6% of the known genotoxicants and nongenotoxicants in the database. Moreover, the concordance between prediction and experimental results for molecules not in the learning set is greater than 78%. PMID- 1602978 TI - Somatic and germline mutagenesis assayed by the unstable zeste-white test in Drosophila melanogaster. AB - This investigation is an attempt to compare mutation rates in germinal and somatic cells by the use of the unstable zeste-white assay in Drosophila melanogaster. In this system it is possible to use the same genetic end point to measure both somatic mutations (aberrantly pigmented spots in the eyes of adult flies) and germinal mutations (males with aberrantly pigmented eyes). We used two mutagens, formaldehyde and methylmethane sulphonate (MMS), to induce mutations and two different routes of mutagen administration, larval feeding and adult feeding, and scored mutations in somatic as well as germinal cells. Both types of tissues were susceptible to MMS mutagenesis, showing elevated frequencies of both germline mutations and eye spots. Formaldehyde, however, gave no increase in the germinal mutation rate but caused somatic mutations. These were found after larval exposure, but also among the offspring of exposed males, as formation of delayed somatic mutations. The results show that somatic cells are much more sensitive in monitoring induced mutations than germinal cells in this system. We also found that spontaneous mutation rate among germinal cells is 200 times higher than that in somatic cells, which presumably is due to the involvement of a mobile element. PMID- 1602979 TI - Uptake of the restriction endonuclease AluI by Chinese hamster ovary cells measured by frequencies of induced chromosomal aberrations: effect of hypertonic concentrations of glycerol and sorbitol. AB - Chinese hamster ovary cells were exposed to the restriction endonuclease AluI in the presence of 2.2 M glycerol or 0.9 M sorbitol using different treatment regimens. Induced chromosomal aberrations were taken as indication for cellular uptake of AluI. The results indicate that cellular uptake of AluI is mediated by vesicles formed during transition of hypertonic to isotonic conditions. Addition of medium leads to breakdown of these vesicles and to liberation of AluI molecules which eventually may reach the chromatin. PMID- 1602980 TI - Industrial genotoxicology group. PMID- 1602981 TI - Involvement of membrane carbohydrates of HeLa cells in the E. coli HB101 (pRI203) invasive pathway. AB - The recombinant plasmid pRI203 carries a Yersinia pseudotuberculosis chromosomal gene that makes E. coli K-12 HB101 strain able to synthetize an outer membrane protein, invasin, which interacts with integrin receptors of eukaryotic cells, enabling this microorganism to penetrate human cultured animal cells. In this study we evaluated the involvement of HeLa cell membrane structural components in the early phases of the invasive pathway of E. coli HB101 (pRI203). When HeLa cell monolayers were treated with several enzymes we showed that trypsin-, proteinase K- and neuraminidase-sensitive components are required for bacterial invasion. Comparison of the ability of simple and complex carbohydrates to inhibit bacterial invasion indicated that N-acetyl neuraminic acid, N-acetyl glucosamine and mucin were the most effective competitive inhibitors. Among glycolipids, gangliosides enhanced bacterial entry in HeLa cells. The results obtained suggest that N-acetyl neuraminic acid and N-acetyl glucosamine containing glycoproteins and/or glycolipids participate as putative HeLa cell binding sites for the penetration process of E. coli HB101 (pRI203). PMID- 1602982 TI - Entry of pyelonephritogenic Escherichia coli into HEp-2 cells due to actin polymerization. AB - This study provides evidence that pyelonephritogenic strains of Escherichia coli, which do not produce soluble hemolysin and possess mannose-resistant hemagglutinating activity, are able to adhere and penetrate to HEp-2 cells. Invasion and intracellular survival were analyzed by transmission electron microscopy and by viable counts after killing of extracellular bacteria by gentamicin. Cytochalasin D, which blocks polymerization of G-actin, markedly reduced the entry of E. coli into the cells and inhibited intracellular mobility of the bacteria. By using indirect fluorescent staining with anti-actin rabbit serum, direct evidence was obtained that interaction with the cytoskeleton of HEp 2 cells is necessary for invasion. PMID- 1602983 TI - Production of toxic shock syndrome toxin-1 (TSST-1) by Staphylococcus aureus strains isolated from humans, animals and foods in Nigeria. AB - The production frequency of toxic shock syndrome toxin-1 (TSST-1) amongst Staphylococcus aureus strains isolated from humans, animals and foods in Nigeria was investigated. Of 1015 strains tested, 120 (11.8%) were positive for TSST-1. Thirty one (16.0%) of 194 strains from human diarrhoea and wounds were positive compared to 47 (7.1%) of 666 isolates from eight animal species. Goat strains were most often positive for this toxin (17.0%). A total of 42 (27.1%) of 155 strains from foods were positive for TSST-1. Regardless of source, phage non typable strains (48.3%) were most common amongst TSST-1 producers followed by strains sensitive to phages in several groups (mixed), 18.3%, and phage group III strains (17.5%). Only 6 were phage group I strains (5.0%). TSST-1 producing strains were mostly resistant to penicillin. Eighty-four (70.0%) TSST-1 producers were also enterotoxigenic with staphylococcal enterotoxin C (SEC) most frequently elaborated as 46 (38.9%) strains were positive. However, 42 (35.5%) and 39 (32.5%) strains producing TSST-1 were also positive for SEA and SEB, respectively. It was concluded that TSST-1 producing strains of S. aureus are widespread in humans, animals and foods in Nigeria and such distribution may play some role in the epidemiology of toxic shock syndrome, the prevalence of which is currently unknown in the environment. PMID- 1602984 TI - Antibiotic susceptibility patterns surveillance and clinical distribution of Enterobacteriaceae. AB - 3700 strains of Enterobacteriaceae clinical isolates were tested by automated devices for susceptibility to several antimicrobial agents widely used in clinical practice. Amikacin demonstrated the greatest in vitro activity whereas ampicillin and mezlocillin were the least active. Finally gentamicin and nalidixic acid had a similar activity to recently introduced cephalosporins. The bacterial species widely isolated were grouped in three clusters according to the clinical body site of isolates: several discrepancies emerged from the study of antibiotic susceptibilities of strains obtained from different body site sources. Source could be correlated with bacterial pattern of resistance. PMID- 1602985 TI - Effect of medium salinity on some chemical constituents of two halophilic Bacillus spp. from Saudi Arabia. AB - The cell envelope amino acids of two moderately halophilic Bacillus isolates (BST and BSF) varied according to medium salinity. Cystine and proline were mostly effected. In both isolates growing in the presence of 6 and 18% NaCl there were more dicarboxylic amino acids than basic amino acids which makes the cell envelope proteins quite acidic. The concentrations of the cell-associated cations (Na+, K+, and Mg2+) were high in both isolates, and varied according to the NaCl concentration. The two isolates contained glucosamine and muramic acid in their cell walls. The amounts of these two sugar derivatives, however, varied with the NaCl concentration. Thin-layer chromatography of phospholipids revealed the presence of cardiolipins, phosphatidylglycerols and phosphatidylethanolamines in the two isolates irrespective of medium salinity. Phosphatidylglycerols and the phosphatidylethanolamines increased on increasing the NaCl concentration of the growth medium. Lysophosphatidylglycerols were detected only in the 6% grown BST cells. Unidentified phospholipids designated X1 (in isolates BSF and BST), X2 (in isolate BST) and X3 (in isolate BSF) were also detected; the concentrations of X1 and X3 were salinity dependent. PMID- 1602986 TI - Phenoloxidase production and vanillic acid metabolism by Zygomycetes. AB - The ability of 23 strains of Zygomycetes to produce extracellular phenoloxidases was examined on solid media by using 10 different reagents. The results varied depending on the reagent and indicated that most of the strains were devoid of phenoloxidase activity. The production of inducible phenoloxidases was demonstrated by the Bavendamm reaction. The study of the biotransformation of vanillic acid in synthetic medium indicated that the reaction most often obtained was the reduction of vanillic acid to vanillyl alcohol. Helicostylum piriforme and Rhizopus microsporus var. chinensis completely metabolized vanillic acid while good transformation was obtained with Absidia spinosa, Cunninghamella bainieri, Mucor bacilliformis, Mucor plumbeus, Rhizopus arrhizus, Rhizopus stolonifer, Syncephalastrum racemosum and Zygorhynchus moelleri. Other strains did not degrade or poorly degraded vanillic acid. Decarboxylation and demethoxylation of this compound was independent of the production of phenoloxidases as in the case of white-rot fungi. Other enzymatic systems might be implicated in this phenomenon. PMID- 1602987 TI - Mice infection with HIV-1: a new mouse model for HIV-1 in vivo research. AB - In mice experimentally infected with 1 x 10(5) UI/mouse of HTLV-IIIB IgM antibodies were detected 10-12 days after the infection, reaching peak values two weeks later; the IgM seratiter progressively decreased thereafter and was negative at ten-eleven weeks. HIV p24 antigen was detected ten-fifteen days after infection and reached peak values five-six weeks later. Antigenemia subsequently decreased and showed an oscillating course with a progressive decrease which persisted throughout the observation period. Two weeks after infection we detected IgG antibodies to the major core protein p24; reactivity to gp41 was observed as early as reactivity to p24 and persisted throughout observation period. The IgG antibodies to all HIV epitopes peaked two-three weeks after infection; the time course showed a decrease after ten weeks, progressively decreasing thereafter. After sixty-five weeks of infection the IgG seratiter value was lower but remained positive. Viruses indistinguishable from HIV were isolated from the peripheral blood mononuclear cells of infected mice 30, 60, 180 days after infection. These seroimmunological and virological data confirm that the immunocompetent mouse may serve as a low-cost reproducible model for HIV-1 in vivo research. PMID- 1602988 TI - Antibiotic resistance and plasmids of some human nasal isolates of Staphylococcus aureus. AB - The Staphylococcus aureus isolates were all susceptible to vancomycin. More than 90% of the isolates were susceptible to rifampicin, ampiclox, methicillin, erythromycin and clindamycin. The isolates were highly resistant to the beta lactamase-sensitive penicillins, that is 91, 93.2 and 70.4% of the isolates were resistant to penicillin, ampicillin and carbinicillin. Twelve plasmids were found in the isolates, the 35 and 11 Mdal plasmids coded for aminoglycosides and tetracycline resistances, respectively. PMID- 1602989 TI - Survival of bifidobacteria from human habitat in acidified milk. AB - Some industrial preparations from milk, such as yogurt, contain bifidobacteria as an additional probiotic element. The acidic environment of these products affects the viability of the bifidobacteria. The survival in acidic environment of one hundred and ten bifidobacterial strains from human habitat was tested. PMID- 1602990 TI - Development of Arthrinium species on several nitrogen sources. AB - The aim of this study was to determine the growth aspects of Arthrinium strains in the presence of several nitrogen sources. The addition of tryptone, peptone or soybean peptone to the culture medium stimulated larger colony diameters in most of the isolates. PMID- 1602991 TI - Effect of storage upon the toxicity of synfuel process waters to bacteria. AB - Storage of synfuel process waters at 4 degrees C for 8 years appeared to reduce the toxicity of these waters to indicator bacteria. When these waters were mixed in the amount of 10 percent process waters to 90 percent sewage, heterotrophic bacteria grew which indicate that storage or aeration may improve the treatability of these waters. PMID- 1602992 TI - Incidence of rabies virus complement-fixing antibodies in unvaccinated dogs, humans and livestock in Anambra State of Nigeria. AB - A total of 376 serum samples from dogs, humans and livestock were examined for complement-fixing (CF) antibodies against rabies virus. High CF antibody titres (up to 1:1024) were detected among unvaccinated dogs aged 3 months and above as in vaccinated ones, thus establishing endemicity of the virus in the area. An antibody titre of 1:128 was detected in the serum of a puppy aged below 3 months and is unlikely to be due to residual maternal antibodies. It rather provides evidence for seroconversion at that age and further establishes endemicity of the virus. Moderate to high CF antibody titres (greater than or equal to 1:64) were detected in 44.9% of the unvaccinated dogs, 6.3% of the cattle and 2.8% of the humans. These antibody titres indicate either exposure to rabies virus or inapparent infection by rabies-related viruses. PMID- 1602993 TI - Isolation of Borrelia burgdorferi from a Lyme seronegative patient in northern Italy: expression of OspB immunodominant proteins on the isolated strain. AB - This paper describes the antigenic characteristics of a strain of Borrelia burgdorferi isolated from a patient seronegative for Lyme borreliosis, in the early stage of the illness. The strain was not recognized by a late serum sample from the patient; the isolate reacted in immunoblotting with some of the monoclonal antibodies directed against the immunodominant antigens of Borrelia burgdorferi. In addition to the OspA antigen this strain carries also the epitopes of OspB proteins, unlike the majority of European Borrelia burgdorferi strains. PMID- 1602995 TI - MNA's position: medical malpractice tort reform. PMID- 1602994 TI - Differential cleavage of surface proteins of Borrelia burgdorferi by proteases. AB - The differential cleavage of surface proteins of Borrelia burgdorferi IRS strains by several proteases was examined. Proteinase K, trypsin, chymotrypsin and thermolysin all cleaved the outer surface protein B (OspB) to undetectable levels by Coomassie Brilliant Blue staining, whereas some residual protein was detected by immunoblotting with polyclonal and monoclonal antibodies. Not even antigenic fragments were detectable by immunoblotting with 1A8 monoclonal antibody reactive with OspB. Less effective or ineffective was the cleavage of OspB by V8 protease and proteinase A, respectively. The outer surface protein A was cleaved only by proteinase K. The effect of trypsin on borreliae viability and adhesion to cultured cells was also studied. The trypsin treatment of borreliae did not impair the viability of organisms which continued to synthesize the cleaved OspB. The attachment of B. burgdorferi to HEp-2 cells was reduced by 41% after treatment with trypsin, whereas preincubation of borreliae with monoclonal antibody 1A8 and guinea pig immune serum reduced the adhesion of borreliae to the cells by 32% and 87%, respectively. PMID- 1602996 TI - A question of individual rights. PMID- 1602997 TI - Cloning and whole nucleotide sequence of the gene for the light chain component of botulinum type E toxin from Clostridium butyricum strain BL6340 and Clostridium botulinum type E strain Mashike. AB - Chromosomal DNAs were extracted from Clostridium butyricum strain BL6340 and Clostridium botulinum type E strain Mashike. The 6.0 Kbp fragment coding for the entire light chain (L) component and the N-terminus of heavy chain (H) component of botulinum type E toxin was obtained from each extracted DNAs after digestion with HindIII. The entire nucleotide sequences for the light chain components of these cloned genes were determined, and the derived amino acid sequences were compared to each other, and with those of botulinum type A, C1, D, and tetanus toxins reported previously. The cleavage site of L and H components of type E toxin was presumed to be Arg-422. In a total of 422 amino acid residues of L component, 17 residues were different between butyricum and type E toxins, and all these differences were found within 200 residues of N-terminus of L component. On the contrary, five regions showing highly homologous sequences were found in L components among these six toxins, and one more region between botulinum type E and tetanus toxins. PMID- 1602998 TI - Studies on osmotic stability of liposomes prepared with bacterial membrane lipids by carboxyfluorescein release. AB - The authors measured the osmotic stability of liposomes prepared with membrane lipids of bacteria, using the osmotic-shock release of entrapped carboxyfluorescein as an indicator. The sub-second physical changes of liposomes suspended in a solution of low osmotic pressure were examined by stopped flow spectrophotometry. The entrapped carboxyfluorescein was released when the liposomes burst on inflow of excess water. Liposomes prepared with the lipids of a stable Staphylococcus aureus L-form strain were more resistant to low osmotic pressure than those prepared from the wild strain of S. aureus, and liposomes prepared from Mycoplasma orale were even more resistant. Cardiolipin enhanced the lipid membrane stability in S. aureus and cholesterol in M. orale. The stability of lipid membranes to low osmotic pressure could be precisely determined by the present method. PMID- 1602999 TI - Heterogeneity of S-layer proteins of Lactobacillus acidophilus strains. AB - An S-layer (surface regular array) was found in the cell wall from six out of ten strains of Lactobacillus acidophilus examined by electron microscopic observations. All of the six strains which were shown to carry the S-layers belonged to the deoxyribonucleic acid (DNA) homology group A, but not to B, which had been classified by Johnson et al (Int. J. Syst. Bacteriol. 30: 53-68, 1980). On the other hand, the other four strains which possessed no S-layers were in the homology group B. The apparent molecular weights of the S-layer proteins ranged from 41 to 49 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Of the S-layer proteins from the six strains, three were susceptible to chemical cleavage with N-chlorosuccinimide, giving different peptide maps. All of the six S-layer proteins were fragmented by limited proteolysis with Staphylococcus aureus V8 protease, and gave markedly different peptide patterns by the subsequent peptide mapping analysis, except that the peptide maps of the S-layer proteins from the two strains which were in the same subgroup were identical. PMID- 1603000 TI - Interferon induction in murine peritoneal macrophage by stimulation with Lactobacillus acidophilus. AB - Induction of interferon for a kind of dairy lactic acid bacteria, Lactobacillus acidophilus (L. acidophilus), was investigated in murine peritoneal macrophage (M phi) cultures. Lactobacillus acidophilus JCM 1034, 1132T, 1229 and 2125 induced IFN (12-34 I.U./ml) in M phi cultures in vitro. Strain 1132T- and 2125-induced IFNs were characterized as IFN alpha/beta by treatment with anti-IFNs serum. The results indicate that the inducing activity of IFNs may be one of the available biological parameters for designating the dairy products containing L. acidophilus as "physiologically functional foods." PMID- 1603001 TI - Gelatin particle agglutination test for early serodiagnosis of Japanese spotted fever. AB - A gelatin particle agglutination (PA) test for Japanese spotted fever has been developed. Gelatin particles were sensitized with a sonicated causative rickettsia and used as antigens. The antibodies by PA test were detected as early as days 4-7 after the onset, whereas those by indirect immunoperoxidase (IP) test were detected after days 8-11. In addition, PA titers were higher than IP titers before days 20-23. The agglutinins detected by PA test were proven to be IgM because they were all sensitive to dithiothreitol. PA test was, however, less specific than IP test, giving a little nonspecific reaction to the sera from patients with scrub typhus and from individuals unrelated to those two rickettsioses. Nevertheless, PA test, which is simple, rapid, and easy to interpret the results, is useful for the early serodiagnosis of Japanese spotted fever. PMID- 1603002 TI - Rational therapeutics: the way ahead. PMID- 1603003 TI - Rubella reinfection--what risk to the fetus? PMID- 1603004 TI - Active and passive smoking. PMID- 1603005 TI - Asthma morbidity in Australia: an epidemiological study. AB - OBJECTIVE: To examine the prevalence and management of asthma in adults and children in a population sample in eastern Australia. SETTING: A random sample of children from 33 primary schools in Sydney, Melbourne, Brisbane, and the Upper Hunter Valley (New South Wales), and their parents. DESIGN: A cross-sectional analytic survey of 8753 primary school children aged between 5 and 12 years, and their parents (n = 13,945 adults). Asthma prevalence and management practices were determined by parental responses to a questionnaire, and spirometry was performed in children with "probable asthma". RESULTS: Of 8753 children whose parents responded, the prevalence of current wheeze was 19.5% and diagnosed asthma was 17.1%. Of the children with "probable asthma", 30% had their lung function measured in the previous year, and 6% possessed both a peak flow meter and an action plan for their asthma. Undertreatment was likely, as preventive asthma medications (inhaled corticosteroids or sodium cromoglycate) were used regularly by only 25.5% of these children and by 44.3% of children who had asthma symptoms more than twice per week. Children with the diagnosis of asthma reported higher rates of preventive medication use and ventilatory function measurement than children with frequent symptoms without the diagnosis. In the 13,945 adults, the reported prevalence of asthma was 7%, of whom 39% were using preventive medications, 34% had their ventilatory function assessed in the previous year, and 7% had both a peak flow meter and an asthma action plan. CONCLUSIONS: The study illustrated the gap between the current level of asthma management in the community and the standards set by the Thoracic Society of Australia and New Zealand. Undertreatment and suboptimal management of asthma remain important problems in Australia. PMID- 1603006 TI - Prevalence of asthma in regional Victorian schoolchildren. AB - OBJECTIVE: To determine whether the high prevalence of reported asthma in Melbourne schoolchildren is seen in rural Victoria. DESIGN: A questionnaire on respiratory symptoms was distributed to children to be completed by parents and returned to the school. Results were compared with a previous Melbourne study. SETTING: Two hundred and twenty-seven government and non-government primary schools in five rural regions of Victoria: coast, wheatbelt, riverland, highland and Latrobe valley. SUBJECTS: All children enrolled in grade 2 were invited to join the study. Parents completed questionnaires for 4661 children after 4886 questionnaires were distributed (response rate, 95%). MAIN OUTCOME MEASURE: History of wheeze in the past 12 months. RESULTS: The overall prevalence of wheeze in the last 12 months was 23.6%. There was a significant difference overall in this rate across the five rural areas and Melbourne, with the Latrobe Valley (26.2%) and highland areas (25.0%) having the highest rate, and the wheatbelt the lowest (19.6%). The spectrum of severity of asthma was similarly distributed across rural regions, although severe episodes were significantly more frequently reported by parents from rural areas than by parents in Melbourne. The reported use of bronchodilators and diagnosis of asthma showed a similar pattern of variation to that of the 12-month prevalence of wheeze. CONCLUSION: The prevalence of asthma in 7-year-old children is similar for rural Victoria as a whole compared with Melbourne, but there is variability in asthma prevalence in individual rural areas which is difficult to account for in terms of known environmental precipitants. PMID- 1603007 TI - Two consecutive thunderstorm associated epidemics of asthma in the city of Melbourne. The possible role of rye grass pollen. AB - OBJECTIVE: To document the clinical impact and identify the meteorological and environmental circumstances surrounding two epidemics of asthma exacerbations associated with thunderstorms in the city of Melbourne and to find a possible aetiology for these events. DESIGN: Collection of meteorological and environmental data from the Victorian Bureau of Meteorology and the Environment Protection Authority; collection of clinical data from metropolitan emergency departments and the Victorian Ambulance Service; and study of a cohort of affected patients with asthma and a control group of asthmatics who were not affected by the storms. SETTING: Tertiary institution. PATIENTS: Twelve storm affected patients with asthma and 16 asthmatics not affected by the storms. INTERVENTION: Administration of a questionnaire, medical interview, pulmonary function tests and skin prick tests with common allergens. MAIN OUTCOME AND RESULTS: Both epidemics caused a major increase in the number of hospital attendances and admissions because of asthma exacerbation (five to ten fold rise). These events could not be related to atmospheric pollution or specific meteorological features of the storms. Patients affected by the second storm were significantly more likely to suffer from hay fever (P less than 0.05), rye grass pollen allergy (P less than 0.05) and allergy to rainfall released rye grass starch granules (P less than 0.025). CONCLUSIONS: Late spring thunderstorms in the city of Melbourne can trigger epidemics of asthma attacks. The seasonal nature of the phenomenon and the pattern of allergic responses found in affected patients suggest a possible aetiological role for rye grass pollen. PMID- 1603008 TI - Are children with asthma affected by smog? AB - OBJECTIVE: To assess the relationship between atmospheric smog and emergency department attendances in children with asthma. DESIGN: The number of child attendances with acute asthma was calculated retrospectively for each day of the 1989 calendar year. Daily smog data for 1989 were then obtained from the Environment Protection Authority of Victoria, and were related statistically to asthma attendances. SETTING: The Emergency Department of the Royal Children's Hospital, Melbourne, which provides primary, secondary and tertiary level health care to the children of Victoria. PATIENTS: All children over two years of age with acute asthma. MAIN OUTCOME MEASURE: The number of attendances with asthma each day for the 1989 calendar year. RESULTS: Smog alerts (smog days predicted by the Environment Protection Authority) and smog episodes (actual smog days of all types) were not significantly related to asthma attendances. A significant relationship was noted, however, between asthma attendances and days when the airborne particulate index was above the acceptable threshold. No relationship was found between asthma attendances and ozone levels (a marker of photo-oxidant smog), or between any smog index and days of unusually high asthma attendance (asthma epidemic days). All smog variables combined explained only 2.3% of the variance in asthma attendance. CONCLUSIONS: Although the overall contribution of smog to asthma attendances in children is small, the correlation between asthma attacks and airborne particles is a hitherto unreported finding in Australia and is potentially of public health importance. PMID- 1603009 TI - Air quality and respiratory disease in Newcastle, New South Wales. AB - OBJECTIVE: To investigate respiratory illnesses in the Newcastle region, their change over time, and their geographic relationship to industrialised areas. DESIGN: We analysed admissions to public hospitals by postcode area in the Newcastle region, for all causes and for all the various respiratory causes, for the years 1979-1988. Comparisons were made between the State of New South Wales and the Newcastle area, and between geographic areas within Newcastle. Changes over the 10-year period were noted. RESULTS: For both all causes and respiratory causes, admission rates to Newcastle hospitals, 1979-1988, were significantly lower than those for the rest of New South Wales in 1986. There was a correlation between living in the industrial part of the city and hospital admission for all causes and respiratory causes. There was also a correlation between mean disposable family income and hospital admissions, with those areas with the higher incomes having lower admission rates. Over the 10 years studied there was a statistically significant decline in admissions for respiratory causes, both in absolute terms and after controlling for changes in admissions for all causes. In children aged 0-14 years a significant increase in admissions for asthma occurred between 1979 and 1988, which could not be explained by diagnostic shift. CONCLUSIONS: On the basis of hospital statistics, the members of the Newcastle population seem little different from those in the remainder of New South Wales. From 1979-1988, the efforts by industry, with the support of the community, to reduce industrial pollution have been accompanied by a reduction in hospital admission rates for respiratory diseases in general and for chronic obstructive lung disease in older people. Other contributing factors include reduced smoking rates and improved medical management. Correlations between geographic location and respiratory admission rates may be a manifestation of social class rather than poor air quality, although a contribution from the latter cannot be discounted. A concomitant rise in asthma admission rates in children aged 0-14 is likely to be unrelated to any change in air quality. PMID- 1603010 TI - Skin disorders in Indo-Chinese immigrants. AB - OBJECTIVE: To define and assess the relative frequency of the skin disorders which were seen in Indo-Chinese immigrants, and to describe in detail some of the interesting cases encountered. DESIGN: Retrospective review of case records of Indo-Chinese immigrants referred to the Lidcombe Hospital Dermatology Centre between October 1987 and March 1991. SETTING: Lidcombe Hospital. PATIENTS: Indo Chinese immigrants assessed at the Lidcombe Hospital Dermatology Centre. RESULTS: One hundred and ninety patients were identified. The most common categories of skin disorders were disorders of pigmentation, disorders of sebaceous glands, and dermatitides. Disorders not often seen in the non-Indo-Chinese population (e.g., naevus of Ota, cutaneous tuberculosis and primary skin-limited amyloidoses) were also identified. No cutaneous malignant conditions were encountered. CONCLUSIONS: Chloasma and acne vulgaris are common dermatological disorders in Indo-Chinese immigrants. Cutaneous malignant diseases do not appear to be common in this population, in contrast to their common occurrence in Caucasian patients. PMID- 1603011 TI - Arthritis in general practice. PMID- 1603012 TI - Accuracy of asthma statistics from death certificates in South Australia. AB - OBJECTIVE: To assess the accuracy of asthma statistics from death certificates in South Australia. DESIGN: Comparison of death certificate coding with expert panel assessments of causes of death after interviews with certifying doctors, regular medical practitioners and close acquaintances of the deceased. SUBJECTS: 261 subjects for whom the term "asthma", "asthmatic" or "asthmaticus" was recorded in Part I or Part II of death certificates lodged in the 24-month period from May 1988. MAIN OUTCOME MEASURES: Sensitivity, specificity and predictive value of death certificate coding, with expert panel assessments as the reference standard. RESULTS: About 95% of deaths assessed as definitely due to asthma were so coded from death certificates, but only 69% of deaths assessed by the panel as not due to asthma were coded to a "non-asthmatic" cause. Of the 129 deaths coded to asthma, the percentage assessed as definitely or likely to be due to asthma was 56%. For ages under 65 years, this figure was 84% compared with only 38% for older subjects. CONCLUSION: The accuracy of death certificate data on asthma for the age group 65 years and over would be too low at present for most epidemiological purposes. PMID- 1603014 TI - Casemix classification and Australian doctors. Risks and opportunities. AB - "Casemix" is an information tool--a set of patient care classifications and ideas about their use. It is useful only if it promotes understanding, and leads to better performance of the health system. Here we discuss some uses of casemix classifications, including payment of hospitals on a per case basis. Clinicians need to be concerned about both the design of casemix classifications themselves, and the ways in which they are used. PMID- 1603013 TI - A casemix of patients undergoing abdominal surgery. AB - OBJECTIVE: To construct a casemix for patients undergoing abdominal surgery. DESIGN: A prospective longitudinal study. Wound infection was chosen as the target adverse event. A cluster analysis identified seven risk factors, which were then incorporated into a Boolean cluster (the casemix). SETTING: Royal Perth Hospital. PATIENTS: 1238 adults. MAIN OUTCOME MEASURES: Wound infection, recurrent intraperitoneal sepsis, hospital stay, admission to the intensive care unit, and death. RESULTS: Measures of the severity of illness and the extent of co-morbidity were more important in determining the risk of a poor outcome than was the identity of the diseased organ. CONCLUSIONS: Estimates of severity of illness and extent of co-morbidity should be included in any casemix based system for patients undergoing abdominal surgery. PMID- 1603015 TI - A potential new technique for awake fibreoptic bronchoscopy--use of the laryngeal mask airway. AB - OBJECTIVE: To assess the potential use of the laryngeal mask airway (LMA) for awake diagnostic fibreoptic bronchoscopy. DESIGN: A prospective study of 50 patients presenting for awake diagnostic bronchoscopy. All patients were premedicated with pethidine and atropine. The LMA was inserted under topical anaesthesia with sedation and the quality of the subsequent laryngoscopy and bronchoscopy was assessed for both patient and bronchoscopist. SETTING AND PATIENTS: All patients over the age of 18 years who presented to Cairns Base Hospital for diagnostic bronchoscopy were asked to participate in the study. MAIN OUTCOME MEASURES: The main factors determining the suitability of the technique were insertion rate, ease of the laryngoscopy and bronchoscopy, oxygen saturation and patient acceptance. RESULTS: The LMA was inserted successfully in all patients and the bronchoscopy subsequently performed. The first time insertion rate was 72%. The mean oxygen saturation during the procedure was 98% and patients tolerated the technique. CONCLUSIONS: The potential advantages of the LMA are that it is simple to insert, avoids nasal trauma and facilitates direct laryngoscopy. It allows respiration to be monitored and oxygen to be administered. The technique may have a role to play in patients whose respiratory function is in a critical condition, but confirmation of this awaits comparative trials. A period of training is recommended in anaesthetised patients before the LMA is used for awake diagnostic bronchoscopy. PMID- 1603016 TI - Congenital rubella after previous maternal vaccination. PMID- 1603017 TI - Fenoterol and death from asthma. PMID- 1603018 TI - Mefloquine resistant P. vivax malaria in PNG. PMID- 1603019 TI - Proguanil combined with dapsone chemoprophylaxis for malaria. PMID- 1603020 TI - Continuous subcutaneous apomorphine infusion in Parkinson's disease. PMID- 1603021 TI - Deterioration in renal function in patients taking lithium and a diuretic. PMID- 1603022 TI - Glue ear and grommets. PMID- 1603023 TI - Tuberculosis in Australia. PMID- 1603024 TI - Tuberculosis in Australia. PMID- 1603025 TI - Tuberculosis in Australia. PMID- 1603026 TI - Diaphragm fibre types in the sudden infant death syndrome. PMID- 1603027 TI - Change "DNR" to "GPC". PMID- 1603028 TI - In search of the pathogenesis of refractory cervicobrachial pain syndrome. PMID- 1603029 TI - [The foundation, birth and first steps of the Clinica del Lavoro of Milan. Its historical and social contexts]. AB - After recalling the precursors of social and occupational medicine and the political and social background at the beginning of the century, the author dedicates his attention to Luigi Devoto, lecturer, researcher and organizer. An account is given of his work, his friends (and opponents) and his divulgatory activity, whereby he was able to stimulate the interest of politicians and administrators in the problems of safeguarding the health of the workers and their workplaces. Thanks to the enthusiastic commitment of Luigi Devoto, and with the support of other eminent physicians such as Luigi Mangiagalli, in 1902 the municipal council of Milan voted, by a very large majority, the concession of municipal land to build the first Clinic for the study and treatment of occupational diseases. Building began in 1907 and 3 years later the Clinic was inaugurated. The Directorship was assigned to Luigi Devoto who described the organization, activity and staff of the Clinic in a wealth of detail in the first report drawn up just 3 years later. PMID- 1603030 TI - [The history and recollections of the 80 years of existence of the Clinica del Lavoro of Milan]. AB - In recalling the most significant events in the history of the Clinica del Lavoro from its inauguration in 1910, the author dedicates special attention to the work of the Clinic in the 35 years of his own Directorship. He summarizes the principal research projects carried out, recalls the social and political events in which the Clinic was directly involved, and explains what he believes were the reasons for its success or what may have curbed its development. Mention is made of all those who, in various capacities and with various commitments, collaborated with the author in managing the different departments of the Clinic. Also mentioned are the pupils who succeeded in university, hospital or private enterprise careers. PMID- 1603031 TI - The death of Prof. Enrico Vigliani. PMID- 1603032 TI - [Medicina del Lavoro. 90 years of a publishing history]. AB - The following piece is meant to widen general knowledge about La Medicina del Lavoro. This is not an analytical history with interpretations and conclusions; it is simply a narration of facts, anecdotes, and details that are often overlooked, and which taken on importance only in retrospect. It is also a pleasurable satisfaction of the author's curiosity, and above all, a tribute to those who ideated and created the journal, people, associations, and printers, thanks to whom the journal, especially during the difficult first years, was able to grow and develop into a specialized tool with a privileged position both in the history of Occupational Medicine in Italy and in the international scientific community. Perhaps the reader will find some imprecise or partial information in this piece, still it has the virtue (at least, such it is deemed) of being based only on what was written in the volumes of the journal; as a matter of choice, no other source was consulted. One needs also to add that the piece dwells prevalently upon the early years of La Medicina del Lavoro, either because they were rich in events or because so many of our current readers are well informed about the recent history of the journal. Finally, since the complete collection of 82 volumes is available to only a few (in particular there is a scarcity of the first few volumes), we have made an enclosure to integrate the bibliographical references with reproductions of some of the more relevant documents. PMID- 1603033 TI - Correlation between decreased collagen production in diabetic animals and in cells exposed to diabetic serum: response to insulin. AB - Collagen production has been shown to be decreased in costal cartilage from nondiabetic animals after incubation with diabetic rat serum. Since collagen was decreased to a similar degree in tissues from diabetic animals, we questioned whether altered collagen production in vivo could be related to altered production induced in vitro. Collagen and noncollagen protein production in articular cartilage from diabetic animals (production in vivo) was compared to protein production in dermal fibroblasts from non-diabetic rats exposed to serum from the same diabetic rats (production in vitro). Diabetes was induced by intravenous administration of 90 mg/kg of streptozotocin into male Sprague-Dawley rats. Cartilage was removed and incubated with [3H]-proline for 2 hours at 37 degrees C (in vivo), while fibroblasts were exposed to experimental serum from individual animals for 24 hours with addition of 5 microCi of [5-3H]-proline for the final 6 hours (in vitro). Collagen and noncollagen protein production were quantitated using purified bacterial collagenase. Collagen production in cartilage decreased to 46% (p less than .01) and noncollagen to 68% (p less than .05) of levels in control animals. Fibroblasts exposed to 2.5% diabetic serum decreased collagen and noncollagen protein production to levels of 30% (p less than .01) and 54% (p less than .05) of production in cells incubated in 2.5% normal rat serum. Correlation between defective collagen production in cartilage from individual rats and the effects of their own serum on collagen production in fibroblasts was significant (r = 0.84, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603034 TI - Synthesis and turnover of proteoglycans by human and bovine adult articular chondrocytes cultured in alginate beads. AB - Human and bovine adult articular chondrocytes cultured in alginate beads or agarose gel retain their spherical shape and typical chondrocytic appearance for at least 5 weeks. Aggrecan is always the major population of proteoglycans (PGs) synthesized; its size varies depending upon the age of the cartilage from which the cells are derived but it is not influenced by the culture system used. Studies of human chondrocytes cultured in alginate showed that the majority of the newly-synthesized aggrecan molecules are rapidly incorporated into aggregates which can be extracted from the gel in their native form. About one-third of the aggregates formed during a 4-hour period of incubation in the presence of [35S] sulfate are packed at high concentration in the cell-associated matrix; the remainder is present in areas of the gel further removed from the cells. Aggrecan appears to be turned over more slowly by human than by bovine cells in both culture systems; in both species, the rate of turnover is slower in alginate than in agarose. Decorin is also synthesized in small amounts but it is rapidly lost from the agarose or alginate gel. PMID- 1603035 TI - Catabolism of hyaluronan in the knee joint of the rabbit. AB - Catabolism of hyaluronan was studied by injecting hyaluronan labelled with [125I] tyramine cellobiose ([125I]-TC) into knee joints of rabbits. After endocytosis [125I]-TC remains intracellularly allowing localization of the site of catabolism. At 6 hours after injection 63% could be recovered in and around the joint, while at 48 hours 32% remained locally. Chromatography showed that 12% of the injected tracer was degraded in joint tissues at 6 hours, increasing to 33% at 24 hours. There was no apparent degradation within the joint fluid. No tracer was found in the regional lymph glands, but 16% of the injected tracer was detected in the liver at 24 hours. This investigation demonstrates that hyaluronan in the joint can be degraded both locally and in the liver. PMID- 1603036 TI - Changes in proteoglycan turnover in experimental canine osteoarthritic cartilage. AB - The metabolism of newly-synthesised and total ("resident") proteoglycans was examined in control and osteoarthritic cartilage explants obtained from an experimental model (Pond and Nuki, 1973) of canine osteoarthritis. The following findings were obtained: (i) Non-labelled proteoglycans extracted from normal cartilage with 4 M guanidine HCl showed two bands visualised by staining with toluidine blue. The electrophoretic mobilities of proteoglycans from osteoarthritic cartilage were unchanged but the relative abundance of the slower migrating band increased with time after surgery. (ii) There were qualitative differences in the proteoglycan breakdown products released into the medium of explant cultures of osteoarthritic compared with control cartilage. This was apparent for both labelled and total unlabelled proteoglycans. (iii) There were similarities in the electrophoretic mobilities of the major labelled and non labelled proteoglycan breakdown products suggesting that total ("resident") proteoglycans and newly-formed proteoglycans were degraded by similar mechanisms. There were however some differences in the labelled and non-labelled proteoglycans, suggesting that the mechanisms of breakdown were not identical. (iv) Immunoblotting techniques showed differences in the distribution of various glycosaminoglycans in proteoglycan breakdown products from control compared with osteoarthritic cartilage explant cultures. (v) Monoclonal antibodies 7-D-4 and 3 B-3 (which recognise unusual native chondroitin sulphate epitopes) showed greatly increased expression on proteoglycans from osteoarthritic cartilage compared with controls. PMID- 1603037 TI - A comparison of the high buoyant density proteoglycans isolated from the intervertebral discs of chondrodystrophoid and non-chondrodystrophoid dogs. AB - Groups of purebred beagles and greyhounds of similar ages (1.5-2.5 years) were used for the study. Intervertebral disc proteoglycans (PGs) were radiolabelled in vivo (with [35SO4(2-)], 24 hours and 60 days prior to euthanasia, when lumbar discs were dissected into nucleus pulposus (NP) and annulus fibrosus (AF). Aliquots of each disc region were separately analysed for total PG content as hexuronate. The remaining tissue was subjected to extraction with 4.0 M GuHCl. High buoyant density PGs were isolated from these extracts by CsCl density gradient ultracentrifugation. The hydrodynamic size and aggregatability of the 24 hour, 60-day-old, and resident PG populations were determined by Sepharose CL2B chromatography in the presence or absence of excess hyaluronic acid. While the hydrodynamic sizes of the newly synthesized (24-hour) disc PG preparations appeared to be similar, the 60-day-old greyhound disc PGs were found to be larger than the corresponding beagle disc PG populations. However, the keratan sulphate core protein complexes prepared by chondroitinase ABC digestion of the newly synthesized (24 hour) disc PGs showed that the greyhound disc preparations were also larger than those from beagle discs. Approximately 80% of the newly synthesized PGs from beagle and greyhound discs were capable of aggregating with hyaluronic acid, however, this was reduced to 55% for the 60 day-old PGs in NP and AF and even less for the resident PG populations (as determined by hexuronate analysis). Significantly, PG aggregation was lower in the greyhound NP and AF preparations than in the corresponding PGs isolated from the beagle disc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603038 TI - Cellular expression of tropoelastin mRNA splice variants. AB - The primary transcript of tropoelastin is alternatively spliced into multiple mRNAs. The pattern and frequency of exon splicing is developmentally regulated, but the cellular profile of isoform expression within and among elastic tissues is not known. We used splice-variant specific antisense oligomeric deoxyribonucleotide probes in an in situ hybridization assay to assess the distribution of cells undergoing specific alternative splicing of tropoelastin pre-mRNA in developing bovine elastic tissues. Antisense oligomers were synthesized to exon sequences that are not alternatively spliced (exon 36) and to sequences that become abutted after high frequency (exon 33) and low frequency (exons 13 and 14) alternative splicing. The specificity of these probes for tropoelastin splice variants was verified by Southern hybridization to tropoelastin cDNAs with known exon deletions, and their specificity for tropoelastin mRNA was demonstrated by Northern hybridization. In situ hybridization with [35S]-labeled oligomers on sections of bovine lobar pulmonary artery and other elastic tissues showed that all elastogenic cells produce multiple forms of tropoelastin mRNA. These observations suggest that the production of tropoelastin isoforms is common to all cells within an elastin tissue and that this multiplicity may not be involved in regional differences in elastic tissue architecture. PMID- 1603039 TI - Alterations of tropoelastin biosynthesis by elastase damage to smooth muscle cell matrices. AB - The effect of porcine pancreatic elastase (PPE)-induced proteolysis of the extracellular matrix on elastin biosynthesis in neonatal rat aortic smooth muscle cell cultures (NRSMC) was examined. The quantity of insoluble elastin remaining in the damaged cultures decreased with increasing amounts of enzyme used, however no significant cell damage was demonstrated. The accumulation of soluble elastin (tropoelastin) was examined in enzyme injured and control cultures by radiolabelling with [3H]-valine for 4 hours. The tropoelastin content of both the cell layer and media were less in injured cultures on the day of injury and up to one week later when compared to control cultures. In addition, experiments in which cultures were radiolabelled for 15 minutes demonstrated that the biosynthesis of tropoelastin was decreased in the enzyme treated cultures. Moreover, the incorporation of radiolabelled elastin into the insoluble matrix also decreased. Steady-state levels of elastin mRNA showed no differences between injured and control cultures, which suggested that elastin synthesis is affected at a translational or post-translational level. PMID- 1603040 TI - Three new polymorphisms at the COL1A2 locus. PMID- 1603041 TI - Abnormalities in the biosynthesis of type III procollagen in cultured skin fibroblasts from two patients with multiple aneurysms. AB - We examined the synthesis of collagenous proteins by cultured skin fibroblasts taken from 14 patients with an abdominal aortic aneurysm and either an aneurysm at a second site (8 patients) or a first order relative with an abdominal aortic aneurysm (6 patients). Fibroblasts were labeled with [3H] proline and, following pepsin digestion of media proteins, the ratio of type I/III collagen was examined by denaturing polyacrylamide gel electrophoresis (SDS-PAGE). With the exception of two patients, the ratio of type I/III collagen in the media of fibroblasts from aneurysm patients was similar to control values (6 controls). In two of the patients, the type I/III collagen ratio was greater than 3 standard deviations from the mean of both control ratios and those of other aneurysm patients. mRNA levels coding for type III procollagen, however, were normal in both patients. Patient #1 (ME) showed reduced type III procollagen on SDS-PAGE analysis of intracellular proteins. Intracellular and media type III procollagen levels were normal in patient #2 (HR), but media type III collagen was reduced by over 50% after digestion with a combination of trypsin and alpha-chymotrypsin for 5 minutes at 36 degrees C. Control type III collagen was only reduced after digestion at 39 degrees C. These data suggest an altered thermal stability of the type III collagen trimer synthesized by this patient, probably due to a mutation in the amino acid sequence. The data presented in this paper suggest that some forms of common abdominal aortic aneurysms may be caused by mutations in the gene coding for type III procollagen. PMID- 1603043 TI - [A study of perforin appearing in human lymphokine-activated killer (LAK) cells derived from spleen and peripheral blood mononuclear cells]. AB - Perforin is regarded as one of the main cytotoxic factors in such cells. We succeeded in cloning human perforin cDNA and recently used it to assess perforin appearing in LAK cells. To derive the LAK cells, mononuclear cells separated from a human spleen were mixed with recombinant interleukin-2 and cultured. Almost no perforin mRNA appeared on day 0 but definitely accelerated on day 1 and tended to decrease on and after day 2. Peak of perforin mRNA observed on day 1 was found to precede cytotoxic activity on K562 and Daudi cells by one day. Similar results were found in LAK cells derived from peripheral blood mononuclear cells. Regarding the expression of perforin mRNA on day 0 as 1, the values on day 1 and 2 were calculated as 3.6 and 1.8, respectively. Immunological staining using an antiperforin antibody revealed perforin in the cytoplasm of large cells formed blasts, this also confirmed derivation of perforin on the protein level. Flow cytometry indicated that cells containing perforin included most CD16+ NK cells and some CD8+ T lymphocytes. The fact that TNF and IFN were simultaneously derived together with perforin suggested that the collective joint effect of these substances results in cytotoxic activity. PMID- 1603042 TI - [Metabolic effects of GFX+BCAA solution in the old aged rats after operation]. AB - Effects of total parenteral nutrition (TPN) on the perioperative metabolism in old aged rats were evaluated. Extremely old rats (over 100 weeks old) and young rats undergoing laparotomy were treated with TPN (200 ml/kg/days, 182 cal/kg/day, 148 nonprotein cal/N ratio) consisting of carbohydrate mixtures (combination of glucose, fructose, and xylitol, 4:2:1 GFX solution) and 10% amino acids solution with 30% of branched chain amino acids (BCAA). Blood, liver, and urine samples were analyzed on 1, 3 postoperative days. Increased body weight, positive balance in daily nitrogen excretion, and decreased water content of the liver were observed in old rats. Protein, glycogen, and triglyceride contents of the liver tissue increased in old rats. However the young rats showed negative nitrogen balance and stronger catabolic effect than the old rats. It suggested negative nutritional balance in young rats with this decreased dosage of GFX+BCAA solution suitable for the old rats. In conclusion, decreased amounts of GFX+BCAA solution improved perioperative metabolism in the extremely old. PMID- 1603044 TI - [Pattern of lymphatic spreading in cancer of the thoracic esophagus--analysis in cases undergoing cervical dissection]. AB - The distribution of involved nodes was analyzed in 110 patients with cancer of the thoracic esophagus undergoing systematic dissection of lymph nodes including cervical nodes. Nodal involvement was found in 75% of cases. The distribution pattern of involved nodes suggested that the esophagus is directly drained by various lymph nodes. Cancer metastasis was commonly found across a considerable longitudinal distance; even across two thirds of the esophagus. Longitudinal metastasis to lymph nodes along the recurrent laryngeal nerves (RLNs): upward metastasis, or the perigastric nodes: downward metastasis, was quite frequent. Especially, the right RLN nodes and cardiac nodes were involved in 40% of cases, respectively. In cases with a solitary involved node or with superficial cancer, such upward or downward metastasis was much more prominent than other metastasis. Surgical results varied with the number of positive nodes and the involved site. Cases with no or one positive node showed similar late results; significantly better than the result in other cases (p less than 0.05). Most of three year survivors with nodal involvement had only upward and/or downward metastasis. Perigastric involvement had less influence on the result than mediastinal involvement. Though the pattern of lymphatic extension in esophageal cancer is apparently quite singular, it seemed to be derived from the fact that the esophagus is directly drained by many widely distributed lymphatic channels which have different clinical meanings. PMID- 1603045 TI - [Proliferative activity in gastric cancer with Ki-67 and propidium iodide: analysis by flow cytometry]. AB - Growth fractions in the cell cycle were demonstrated by flow cytometry with monoclonal antibody Ki-67 for gastric cancer. By setting the cut off line at the lowest channel number of S-phase, the Ki-67 labeling rate was calculated by Ki DNA dual fluorescence analysis. In addition to 32 gastric cancers, we examined three cell lines (Colo 320, NUGC4 and MKN28) and compared the result with the BrdUrd labeling rate. The G0G1 ratio obtained with BrdUrd was generally correlated with the G0 + G1 ratio obtained with Ki-67. The S-phase fractions obtained with Ki-67, however were a little different from those obtained with BrdUrd because of the existence of S0. The mean Ki-67 labeling rate of gastric cancer was 45.1% (16.2-66.3%). Fifteen cases received Ki-67 immunohistochemical study in the same samples. The results of flow cytometric analysis were parallel to those of microscopic study, and a correlation line: y = 0.626x + 15.9145, r = 0.8031, (p less than 0.001) was obtained. Ki-67 antibodies may provide useful information on cell kinetics. PMID- 1603046 TI - [Recurrent peptic ulcer after surgery in Japan--a nationwide questionnaire survey of 57 institutions]. AB - Patients with recurrent peptic ulcer undergoing surgery were reviewed at 57 institutions by the 18th meeting of the Japanese Research Society of Gastric Surgery. The factors involved in recurrence was analyzed in patients fulfilling the following criteria: the minimum follow-up period was over 5 years, the age was over 15 years, tetragastrin-stimulated acid secretion was measured before surgery, and the recurrence was confirmed by endoscopy or upper gastrointestinal radiography. In 632 patients, the recurrence rate of duodenal ulcer was significantly higher than that of gastric ulcer. However, the duodenal ulcer patients undergoing selective vagotomy and antrectomy did not develop recurrence. A significant difference in the recurrence rate was observed between selective vagotomy and antrectomy and the wide gastrectomy or selective proximal vagotomy. By analysis using the Cox proportional hazard model, the risk factors for recurrence of duodenal ulcer were the ulcer stage, the operative procedure, the location of the ulcer, and the age of the patient. Especially, recurrences in patients receiving selective proximal vagotomy depended on the location of the ulcer and the age, but the risk factors for patients undergoing wide gastrectomy were uncertain. PMID- 1603047 TI - [A comparative analysis of interval breast cancer with breast cancer detected by mass screening or in outpatient clinics]. AB - To investigate the characteristics and the prognosis of interval breast cancer, 21 interval cases were reviewed and compared with a total of 87 patients with breast cancer detected by mass screening and 266 found in outpatient clinics on the basis of the clinicopathological features. The postoperative cumulative 7 year disease-free rates were 61.1%, 81.4% and 69.0% in the interval cases, mass screening cases and outpatient clinic cases, respectively. The percentage of cases showing frequent mitoses in cancer cells was statistically higher for interval cancer than for the other breast cancers. The average tumor size of the interval cases calculated from the speculated tumor doubling times, was 1.51 cm. It is surmised that interval breast cancer is characterized by a marked proliferation of tumor cells and has a poorer prognosis than the other breast cancers. This might be due to the marked proliferation of interval breast cancer rather than under-counting because there were no malignant findings at the time of the last screening. PMID- 1603048 TI - [Development of a method to prevent degenerative changes of the vein graft for arterial reconstruction]. AB - Autologous vein graft is frequently used for arterial reconstruction in vascular surgery. Its' long-term patency rate, however, is low because of the degenerative changes of the vein wall. Of the basis of our hypothesis that the degenerative changes are mainly caused by an over-distension of vein wall in arterial system, in this study, autologous vein grafts of rabbit (N = 56) were implanted in the carotid arteries. To prevent overdistension, some of the grafts were covered with prosthesis which was made of microporous, compliant biodegradable polyurethane and were compared with those without prosthesis. The integrity of the architecture of the vein wall covered with prosthesis was well preserved at 6 weeks after implantation, where the biodegradation of prosthesis induced an optimal arterialization of the vein grafts. The results indicate that this method may prevent the degenerative changes of vein wall such as fibrosis and intimal hyperplasia, which would cause poor long-term patency of vein graft used for arterial reconstruction. PMID- 1603049 TI - [Hyperbaric oxygenation therapy for chronic occlusive arterial diseases of the extremities]. AB - Therapeutic effects of hyperbaric oxygen therapy (HBO) in 50 patients with chronic occlusive arterial diseases were studied with determination of the transcutaneous oxygen pressure (TcPO2), plasma lipid peroxide level, and plasma superoxide dismutase (SOD) level. Necrosis or ulceration was present in 30 patients, rest pain without tissue loss in 6, infection and necrosis in 2, infection of the amputated stump in 2, delayed healing of the amputated stump wound in 8, and delayed union of bone fractures in 2. HBOs were carried out in 2 3 absolute atmospheres for 60 min for 3-40 times (mean, 12.7 times). In combination with HBO, sympathetic denervation was performed in 41 patients, and PGE1 infusions were administered in 46. Of patients with necrosis or ulceration, 16 were healed, 13 were improved, and one was unchanged. Of patients with rest pain, 5 had relief and one was unchanged. All patients with infection were cured. Of patients with delayed healing of amputation wounds, 7 were healed and one required reamputation. All patients with bone fractures obtained bone union. The TcPO2 markedly increased during HBO and remained at a high level for some time after HBO. The lipid peroxide and SOD levels were not changed significantly by HBO. PMID- 1603050 TI - [A cases of antithrombin III (ATIII) deficiency associated with extrahepatic portal occlusion undergoing operation for esophgogastric varices]. AB - A 23-year-old woman developed thrombosis of the superior mesenteric vein and underwent an extensive enterectomy. She was diagnosed to have ATIII deficiency with extrahepatic portal vein thrombosis and esophagogastric varices. She was admitted to our department and underwent esophageal mucosal transection and splenectomy. Her activities of ATIII were 46%, but ATIII activities of her family were over 90%. ATIII activities during perioperative period were kept more than 70% following administration of ATIII drug. After splenectomy thrombocythemia which was over 300 x 10(4)/mm3 appeared with severe headache and slight pain of hands. She was discharged on 76th postoperative day with no complications and collapse of esophageal varices. PMID- 1603051 TI - [Lobular carcinoma of the male breast--a case report]. AB - Lobular carcinoma of the male breast is very rare, because lobules do not exist in the male mammary gland. Seven cases of lobular carcinoma of the male breast have been reported in Europe and U.S.A., although no case in Japan. We encountered a very rare case of the lobular carcinoma of 74-year-old male breast. Histopathological examinations of both primary tumor and recurrent tumors of the skin led to the diagnosis of lobular carcinoma. PMID- 1603052 TI - [A case report of true palmar aneurysm]. AB - True palmar aneurysm is a rare disease of the hand. Only 12 cases of true palmar aneurysm have been reported in Japan. This occurs commonly in the hypothenar region. We experienced a 12-year-old boy who had a aneurysm of the left palmar hand successfully treated by surgery. The clinical diagnosis was established by ultra sound. Vascular reconstruction by end to end anastomosis was performed after excision of aneurysm. Pathology revealed this was true aneurysm. PMID- 1603054 TI - The identification of the Bs breakpoint and of two possible Bar genes. AB - Two coding regions were identified within a 110 kb region which includes all mapped Bar breakpoints. Both lie proximal to the identified Bar breakpoints. The first coding region, designated BarA, is 5 kb from the most proximal Bar mutation, B581, and 66 kb from the Bs breakpoint. It encodes a 1.3 kb transcript, which is found in late third instar larvae but is absent in 1-3-day-old pupae. Bi, R(B)hd3, B85c15, and Bs result in overproduction of this transcript in late third instar larvae. A second coding region, which was previously identified as BarH1, maps 18 kb from B581 and 79 kb from the Bs breakpoint. In third instar larvae, the abundance of the BarH1 transcript is very low in both wild type and various Bar mutatants, with the exception of R(B)hd3. In 1-3-day-old pupae, the level of the BarH1 transcript is higher. BarH1 was previously identified as the Bar gene. However, this report raises the possibility that BarA rather than BarH1 is the Bar gene or that more than one gene may be involved in Bar position effects. PMID- 1603053 TI - Surrogate transformation of perennial ryegrass, Lolium perenne, using genetically modified Acremonium endophyte. AB - Conditions have been developed for transforming protoplasts of the perennial ryegrass endophyte Acremonium strain 187BB. Unlike most other ryegrass endophytes, this strain does not produce the lolitrem B neurotoxin and is therefore suitable as a host for surrogate introduction of foreign genes into grasses. Transformation frequencies of 700-800 transformants/micrograms DNA were obtained for both linear and circular forms of pAN7-1, a hygromycin (hph) resistant plasmid. Up to 80% of the linear transformants were stable on further culturing but only 25% of the circular transformants retained hygromycin resistance. Integration of pAN7-1 into the genome was confirmed by Southern blotting and probing of genomic digests of transformant DNA. Both single and tandemly repeated copies of the plasmid were found in the genome and both the number and sites of integration varied among the transformants. At least 13 chromosomes were identified in 187BB using contour-clamped homogeneous electric field (CHEF) gel electrophoresis. Probing of Southern blots of these gels confirmed that pAN7-1 had integrated into different chromosomes. The beta glucuronidase (GUS) gene, uidA, was also introduced into 187BB by co transformation of pNOM-2 with pAN7-1. GUS activity was detected by growing the transformants on plates containing 5-bromo-4-chloro-3-indolyl beta-D-glucuronic acid and by enzyme assays of mycelial extracts. Several hph- and uidA-containing transformants were reintroduced into ryegrass seedlings and expression of GUS visualized in vivo, demonstrating that 187BB can be used as a surrogate host to introduce foreign genes into perennial ryegrass.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603055 TI - Selection and analysis of non-interactive mutants in the Escherichia coli tryptophan synthase alpha subunit. AB - The inherent infidelity of Taq DNA polymerase in the polymerase chain reaction was exploited to produce random mutations in the trp A gene. Screening of the resulting clones allowed selection of non-interactive mutant alpha subunits retaining their intrinsic catalytic activity. Two single changes responsible for this phenotype were identified by DNA sequencing as: alpha 126 valine (GTG)--- glutamic acid (GAG) and alpha 128 valine (GTT)----aspartic acid (GAT). Three single changes giving a non-interactive phenotype with an impaired intrinsic catalytic activity were identified by DNA sequencing as alpha 66 asparagine (AAC) ---aspartic acid (GAC); alpha 109 lysine (AAA)----arginine (AGA); alpha 118 cysteine (TGC)----arginine (CGC). Where possible, we individually assessed the importance of these residues in alpha beta interaction in light of structural information from X-ray crystallography and by intergeneric protein sequence comparison. PMID- 1603056 TI - The NAM8 gene in Saccharomyces cerevisiae encodes a protein with putative RNA binding motifs and acts as a suppressor of mitochondrial splicing deficiencies when overexpressed. AB - We have characterized the nuclear gene NAM8 in Saccharomyces cerevisiae. It acts as a suppressor of mitochondrial splicing deficiencies when present on a multicopy plasmid. The suppressed mutations affect RNA folding and are located in both group I and group II introns. The gene is weakly transcribed in wild-type strains, its overexpression is a prerequisite for the suppressor action. Inactivation of the NAM8 gene does not affect cell viability, mitochondrial function or mitochondrial genome stability. The NAM8 gene encodes a protein of 523 amino acids which includes two conserved (RNP) motifs common to RNA-binding proteins from widely different organisms. This homology with RNA-binding proteins, together with the intronic location of the suppressed mitochondrial mutations, suggests that the NAM8 protein could be a non-essential component of the mitochondrial splicing machinery and, when present in increased amounts, it could convert a deficient intron RNA folding pattern into a productive one. PMID- 1603057 TI - Pollen-derived rice calli that have large deletions in plastid DNA do not require protein synthesis in plastids for growth. AB - Albino rice plants derived from pollen contain plastid genomes that have suffered large-scale deletions. From the roots of albino plants, we obtained several calli containing homogeneous plastid DNA differing in the size and position of the deletion. DNA differing in the size and position of the deletion. Southern blotting and pulsed field gel electrophoresis experiments revealed that the DNAs were linear molecules having a hairpin structure at both termini, existing as monomers (19 kb) or dimers, trimers and tetramers linked to form head-to-head and tail-to-tail multimers. This characteristic form is similar to that of the vaccinia virus, in which the replication origin is thought to lie at or near the hairpin termini. Furthermore, polymerase chain reaction experiments revealed complete loss of the ribosomal RNA genes of the plastid DNA. The results suggest that plant cells can grow without translation occurring in plastids. All of the deleted plastid DNAs commonly retained the region containing the tRNA(Glu) gene (trnE), which is essential for biosynthesis of porphyrin. As porphyrin is the precursor of heme for mitochondria and other organelles, it is considered that trnE on the remnant plastid genome may be transcribed by an RNA polymerase encoded on nuclear DNA. PMID- 1603058 TI - Active transcription from a promoter positioned within the coding region of a divergently oriented gene: the tobacco chloroplast rpl32 gene. AB - A new transcription unit has been identified and characterized in the small single-copy region of tobacco chloroplast DNA. A primary transcript (1550 nucleotides) spanning the entire transcription unit contains no significant open reading frames (ORFs), other than ORF55, recently identified as the gene encoding the ribosomal protein CL32 (rpl32). The leader sequence extends 1101 nucleotides from the rpl32 initiation codon. Primer extension and in vitro capping experiments in combination with ribonuclease protection assays, revealed a promoter situated more than 322 bp inside the coding region of ndhF, which is divergently oriented with respect to rpl32. A canonical Pribnow-box is found just upstream of the transcription start site, but a typical -35 motif was not detected. This is the first internal divergent promoter to be characterized in the chloroplast genome. PMID- 1603059 TI - Identification of new sex pheromone plasmids in Enterococcus faecalis. AB - We describe the identification of the following new sex pheromone plasmids in Enterococcus faecalis: a haemolysin-bacteriocin plasmid, pIP964; three R plasmids, pIP1017, pIP1438 and pIP1440; and two cryptic conjugative plasmids, pIP1141 and pMV120. The identification was based on the formation of cell aggregates on filter membranes during conjugation, on efficient transfer in broth matings, and on a positive clumping reaction of cells carrying these plasmids. In addition these plasmids hybridized with DNA probes specific for sex pheromone induced structural genes encoding surface proteins required for conjugative transfer of the plasmids. PMID- 1603060 TI - Sex pheromone plasmid pAD1-encoded surface exclusion protein of Enterococcus faecalis. AB - During conjugative transfer of sex pheromone plasmids of Enterococcus faecalis a so-called surface exclusion protein reduces the frequency with which these plasmids are transferred to cells already possessing the same plasmid. We report here the DNA sequence of a 3.8 kb fragment of the sex pheromone plasmid pAD1 containing the structural gene sea1 for surface exclusion protein and a small open reading frame (ORF) upstream of sea1. Surface exclusion protein Sea1 was found to be highly homologous to the surface exclusion protein Sec10 encoded by the sex pheromone plasmid pCF10. Hybridization studies with DNA probes derived from the structural gene sea1 demonstrated that, with the exception of pAM373, all known sex pheromone plasmids carry a homologous gene. These studies also indicated that the genetic organization is similar in these plasmids, with the structural gene for surface exclusion protein being located 5' to that for aggregation substance. PMID- 1603062 TI - Expression of variant nuclear Arabidopsis tRNA(Ser) genes and pre-tRNA maturation differ in HeLa, yeast and wheat germ extracts. AB - We have recently identified a tRNA gene cluster in the Arabidopsis nuclear genome. One tRNA(Ser) (AGA) gene and two tRNA(Tyr) (GTA) genes occur in tandem arrangement on a 1.5 kb unit that is amplified about 20-fold at a single chromosomal site. Here we have studied the in vitro expression of seven individually cloned tRNA(Ser) genes (pAtS1 to pAtS7) derived from this cluster. Five out of the seven tRNA(Ser) genes contain point mutations in the coding region which have in part adverse effects on the expression of these genes in different cell-free systems: (i) C10 and A62 in plant tRNA(Ser) genes, which correspond to G10 and C62, respectively, in all known vertebrate tRNA genes, result in a reduced transcription efficiency in HeLa but not in yeast extract. This indicates that yeast RNA polymerase III tolerates nucleotide substitutions at positions 10 [5' internal control region (ICR)] and 62 (3' ICR), whereas the vertebrate RNA polymerase III requires a more stringent consensus sequence. (ii) Processing of a pre-tRNA(Ser) with a mismatch in the aminoacyl stem is impaired in HeLa, yeast and wheat germ extracts, however, a mismatch in the anticodon stem is deleterious for HeLa and wheat germ but not for yeast processing enzymes. The unexpectedly high number of potential tRNA(Ser) pseudogenes in the cluster - quite in contrast to the tRNA(Ser) genes which mainly code for functional tRNAs - suggested that tRNA(Ser) (AGA) genes also occur elsewhere in the genome. We present evidence that single copies of tRNA(Ser) (AGA) genes do indeed exist outside the tRNA gene cluster. PMID- 1603061 TI - Characterization of the cea gene of the ColE7 plasmid. AB - The complete nucleotide sequence (1731 nucleotides) of the gene encoding colicin E7 (cea) of plasmid ColE7-K317 was determined. This sequence encoded a deduced polypeptide of 576 amino acids of molecular weight 61349 Da. Comparison of the nucleotide and amino acid sequences of cea E7 with those of other E-group colicins revealed that colicin E7 was closely related to colicin E2, both in gene sequence and in predicted secondary structure of the deduced protein. Judging from the results of cross-immunity tests, we postulated that ColE7 is probably a proximate ancestor of ColE2 and ColE8. Based on results from colicin production tests on cells harboring a 5' end deleted form of the cea E7 gene, we propose that a previously unknown, non-inducible promoter may be involved in regulation of the constitutive expression of the cea E7 gene. PMID- 1603063 TI - Methanococcus voltae harbors four gene clusters potentially encoding two [NiFe] and two [NiFeSe] hydrogenases, each of the cofactor F420-reducing or F420-non reducing types. AB - Four gene clusters were identified in Methanococcus voltae which probably all encode hydrogenases of the [NiFe] type. One of these contains four genes, including those for the three subunits of the known [NiFeSe] hydrogenase capable of reducing the natural deazaflavin cofactor F420. In a second homologous cluster, the gene encoding the subunit corresponding to that which contains selenium in the known enzyme has a cysteine codon in the relevant position. In addition, two more gene clusters were detected which are very similar both in gene order and sequence to one which encodes a hydrogenase that reduces viologens in Methanobacterium thermoautotrophicum, but whose natural electron acceptor is as yet unknown. Again, in one of these clusters, one of the structural genes, which codes for a hydrogenase subunit containing the putative Ni-binding site, contains a selenocysteine codon. The homologous gene in the other clusters again shows a cysteine codon in the corresponding location. The four gene clusters are closely linked. Those encoding the two selenium-free enzymes are arranged in opposite polarities with a relatively short intergenic region. This arrangement is discussed in terms of a possible joint transcriptional regulation. PMID- 1603064 TI - Identification of a new EF-hand superfamily member from Trypanosoma brucei. AB - We identified several open reading frames between the regions encoding calmodulin and ubiquitin-EP52/1 in the genome of Trypanosoma brucei. One of these, EFH5, encodes a protein 192 amino acids long. The EFH5 transcript is present in poly(A)+ mRNA and is present at similar levels in the mammalian bloodstream form and the insect procyclic form. EFH5 contains four EF-hand homolog domains, two of which are inferred to bind Ca2+ ions. We expressed EFH5 as a fusion protein in Escherichia coli and demonstrated calcium-binding activity of the fusion protein using the 45Ca-overlay technique. The function of EFH5 remains unknown; however, as the fourth EF-hand homolog identified in trypanosomes, it attests to the broad range of functions assumed by calcium functioning as a second messenger. EFH5, which is most closely related to LAV1-2 from Physarum, represents a distinct subfamily among the EF-hand-containing proteins. PMID- 1603065 TI - Functional analysis of the expression of the 3'-phosphoglycerate kinase pgk gene in Aspergillus nidulans. AB - A functional analysis of the Aspergillus nidulans 3-phosphoglycerate kinase pgk promoter was undertaken using gene fusions to the lacZ gene of Escherichia coli, and introducing these into a beta-galactosidase-deficient strain of A. nidulans. Expression of a particular gene fusion in transformed strains depends upon the site of integration of the vector into the genome, and when specifically targeted to the catabolic quinate dehydrogenase qutE (selective marker) locus is directly proportional to its copy number. The analysis of transformed strains with single copies of pgk promoter deletion--lacZ fusions at the qutE locus identified three constitutive, positively acting sequence elements in the pgk gene. Sequence located between -161 and -120 nucleotides relative to the transcript start site +1, and including an element with a seven-out-of-eight nucleotide match (AAGCAAAT; -131 to -124) to the consensus eukaryotic octamer sequence ATGCAAAT, is essential for expression, and deletion of the complete 41-nucleotide sequence abolishes transcription. Sequence encompassing codons 14 to 183 and including the two introns of pgk contributes approximately one-third of the total activity, and far upstream sequence 5' to position -638 contributes approximately a further one third total activity. In addition, sequence located -638 to -488 nucleotides, which includes an apparent consensus feature of A. nidulans glycolytic genes, affects carbon source-dependent regulation of expression. This region is required for an approximately 50% increase in pgk expression when A. nidulans is grown on gluconeogenic compared with glycolytic carbon sources. PMID- 1603066 TI - Genetic and molecular analysis of the dpy-14 region in Caenorhabditis elegans. AB - Essential genes have been identified in the 1.5 map unit (m.u.) dpy-14-unc-29 region of chromosome 1 in Caenorhabditis elegans. Previous work defined nine genes with visible mutant phenotypes and nine genes with lethal mutant phenotypes. In this study, we have identified an additional 28 essential genes with 97 lethal mutations. The mutations were mapped using eleven duplication breakpoints, eight deficiencies and three-factor recombination experiments. Genes required for the early stages of development were common, with 24 of the 37 essential genes having mutant phenotypes arresting at an early larval stage. Most mutants of a gene have the same time of arrest; only four of the 20 essential genes with multiple alleles have alleles with different phenotypes. From the analysis of complementing alleles of let-389, alleles with the same time-of arrest phenotype were classified as either hypomorphic or amorphic. Mutants of let-605, let-534 and unc-37 have both uncoordinated and lethal phenotypes, suggesting that these genes are required for the coordination of movement and for viability. The physical and genetic maps in the dpy-14 region were linked by positioning two N2/BO polymorphisms with respect to duplications in the region, and by localizing the right breakpoint of the deficiency hDf8 on the physical map. Using cross-species hybridization to C. briggsae, ten regions of homology have been identified, eight of which are known to be coding regions, based on Northern analysis and/or the isolation of cDNA clones. PMID- 1603067 TI - Different mechanisms generating sequence variability are revealed in distinct regions of the hydroxyproline-rich glycoprotein gene from maize and related species. AB - The sequences of the genes coding for a hydroxyproline-rich glycoprotein from two varieties of maize (Zea mays, Ac1503 and W22), a teosinte (Zea diploperennis) and sorghum (Sorghum vulgare) have been obtained and compared. Distinct patterns of variability have been observed along their sequences. The 500 bp region immediately upstream of the TATA box is highly conserved in the Zea species and contains stretches of sequences also found in the sorghum gene. Further upstream, significant rearrangements are observed, even between the two maize varieties. These observations allow definition of a 5' region, which is common to the four genes and is probably essential for their expression. The 3' end shows variability, mostly due to small duplications and single nucleotide substitutions. There is an intron present in this region showing a high degree of sequence conservation among the four genes analyzed. The coding region is the most divergent, but variability arises from duplications of fragments coding for similar protein blocks and from single nucleotide substitutions. These results indicate that a number of distinct mechanisms (probably point mutation, transposon insertion and excision, homologous recombination and unequal crossing over) are active in the production of sequence variability in maize and related species. They are revealed in different parts of the gene, probably as the result of the different types of functional constraints acting on them, and of the specific nature of the sequence in each region. PMID- 1603068 TI - Comparative sequence analysis of the Clostridium difficile toxins A and B. AB - The six clones pTB112, pTB324, pTBs12, pCd122, pCd14 and pCd13 cover the tox locus of Clostridium difficile VPI 10463. This region of 19 kb of chromosomal DNA contains four open reading frames including the complete toxB and toxA genes. The two toxins show 63% amino acid (aa) homology, a relatedness that had been predicted by the cross-reactivity of some monoclonal antibodies (mAb) but that is in contrast to the toxin specificity of polyclonal antisera. A special feature of ToxA and ToxB is their repetitive C-termini. We define herein 19 individual CROPs (combined repetitive oligopeptides of 20-50 aa length) in the ToxB C-terminus, which are separable into five homologous groups. Comparison of the aa sequences of the N-terminal two-thirds of ToxA and ToxB revealed three marked structures, a cluster of 172 hydrophobic, highly conserved aa in the centre of both toxins, a sequence of 120 residues with an accumulation of highly conserved arginine, cysteine, histidine, methionine, and tryptophan residues, and a stretch of 248 less conserved aa. The probable function of these domains is discussed. Structural and functional homologies of ToxA and ToxB indicate that both genes have a common ancestor and may have evolved by gene duplication, with subsequent recombination and mutation, as has been reported for streptococcal glucosyltransferases (Gtf). PMID- 1603069 TI - DNA sequence and transcription of an endoglucanase gene from Prevotella (Bacteroides) ruminicola AR20. AB - The endoglucanase gene was sequenced from Prevotella ruminicola AR20, isolated as clone pJW4. The endoglucanase (BrEND) is encoded by an open reading frame (ORF1) of 501 codons, corresponding to a protein of calculated molecular weight 55.7 kDa. Analysis of proteins on SDS-PAGE revealed a protein corresponding to the calculated molecular weight of the processed BrEND. The protein showed substantial homology to members of the A4 sub-family cellulases. Primer extension studies revealed that transcription of celA is initiated at different sites in Escherichia coli and Prevotella ruminicola. E. coli sigma 70 recognition sequences were identified, which were located upstream from the transcription initiation site (TIS) functional in E. coli. A longer extension product was identified using RNA from P. ruminicola, indicating that the gene may normally be transcribed as part of a polycistronic message. The end of the primer extension product corresponded to a site beyond the 5' boundary of the cloned fragment, thus preventing identification of native promoter sequences. A second ORF of 110 codons (ORF2) was identified on the antisense strand, and primer extension indicated that transcription through ORF2 was initiated at an identical site in both E. coli and P. ruminicola. E. coli-like consensus sequences were located at positions -10 and -35 upstream from this site, suggesting that some promoter sequences in P. ruminicola are similar to E. coli consensus sequences, although others recognized by E. coli are non-functional in P. ruminicola.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603070 TI - Characterization of two circular plasmids from the marine diatom Cylindrotheca fusiformis: plasmids hybridize to chloroplast and nuclear DNA. AB - This paper reports the discovery and initial characterization of two small plasmids, pCf1 and pCf2, in the marine diatom Cylindrotheca fusiformis. Extracted diatom DNA separates into two bands in CsCl-Hoechst 33258 dye gradients. Upon agarose gel electrophoresis of a sample of the upper band of the gradient we observed, in addition to high molecular weight (genomic) chloroplast and mitochondrial DNA, pairs of lower molecular weight bands. These bands contained two species of circular plasmid DNA molecules, as shown by electron microscopy. The nucleotide composition of the plasmids, and chloroplast and mitochondrial DNAs is similar, as indicated by their co-banding in the gradients. They were cloned, and their restriction maps determined, showing that pCf1 is 4.27 and pCf2 4.08 kb in size. By hybridization analysis, we showed that pCf1 and pCf2 share regions of similarity, but not identity. Neither plasmid hybridizes with mitochondrial DNA. Both plasmids hybridize with chloroplast DNA, and pCf2 also hybridizes with nuclear DNA. PMID- 1603071 TI - Identification of a nodD-like gene in Frankia by direct complementation of a Rhizobium nodD-mutant. AB - Clones from a Frankia At4 gene bank were pooled into groups and mass conjugated into a nodD mutant of Rhizobium leguminosarum bv. viciae by triparental matings. When peas were inoculated with the pooled transconjugants, nodulation was observed. A plasmid, pAt2GX containing Frankia DNA, was isolated from bacteria recovered from these nodules. This plasmid was shown to complement a nodD mutant of R. leguminosarum bv. viciae. Thus pAt2GX contains a Frankia gene that is functionally equivalent to nodD of R. leguminosarum bv. viciae. PMID- 1603072 TI - The yeast RNA1 protein, necessary for RNA processing, is homologous to the human ribonuclease/angiogenin inhibitor (RAI). AB - Mutations in the RNA1 gene of Saccharomyces cerevisiae, which encodes an essential cytosolic protein, affect the production and processing of all major classes of RNA. The mechanisms underlying these effects are not at all understood. Detailed comparative sequence analyses revealed that the RNA1 protein belongs to a superfamily, the members of which contain repetitive "leucine-rich motifs" (LRM). Within this superfamily RNA1 is most closely related to the ribonuclease/angiogenin inhibitor (RAI), which is a tightly binding inhibitor of ribonucleolytic activities in mammals. These results not only provide important clues to the structure, function and evolution of the RNA1 protein, but also have intriguing implications for possible novel functions of RAI. PMID- 1603073 TI - Activation and quantitative estimation of bacteriophage T4 late regulatory signal in cis- and transconditions. AB - Activation of the bacteriophage T4 late gene 22 carried on the phage genome (ciscondition) or borne on a plasmid (transcondition) was quantitatively analyzed after phage infection using a lacZ reporter gene. Transcription from the late promoter was activated postreplicatively by concomitantly infecting T4 phage. A truncated T4-lacZ gene including only 15 bp of sequence upstream of the late promoter consensus of gene 22 TATAAATA, was fully activated in the ciscondition but induced to a reduced extent in the transcondition. A possible mechanism for trans-activation is discussed. PMID- 1603074 TI - The Saccharomyces cerevisiae GAM2/SIN3 protein plays a role in both activation and repression of transcription. AB - We have cloned GAM2, which is required for transcription of STA1, a gene encoding an extracellular glucoamylase in Saccharomyces cerevisiae var. diastaticus. DNA sequence analysis revealed that GAM2 is the same gene as SIN3, known to be a general negative regulator of yeast genes. RNA blot analysis indicated that GAM2/SIN3 also acts as a positive regulator of GAM3/ADR6, which in turn is required for transcription of STA1 and ADH2. These results suggest that GAM2 regulates STA1 expression through transcriptional activation of GAM3 and indicate that GAM2/SIN3 protein is a transcriptional regulator that can play a role in both activation and repression of transcription. PMID- 1603075 TI - Functional analysis of the cysteine motifs in the ferredoxin-like protein FdxN of Rhizobium meliloti involved in symbiotic nitrogen fixation. AB - The Rhizobium meliloti fdxN gene, which is part of the nifA-nifB-fdxN operon, is absolutely required for symbiotic nitrogen fixation. The deduced sequence of the FdxN protein is characterized by two cysteine motifs typical of bacterial-type ferredoxins. The Fix-phenotype of an R. meliloti fdxN::[Tc] mutant could be rescued by the R. leguminosarum fdxN gene, whereas no complementation was observed with nif-associated genes encoding ferredoxins from Bradyrhizobium japonicum, Azotobacter vinelandii, A. chroococcum and Rhodobacter capsulatus. In addition to these heterologous genes, several R. meliloti fdxN mutant genes constructed by site-directed mutagenesis were analyzed. Not only a cysteine residue within the second cysteine motif (position 42), which is known to coordinate the Fe-S cluster in homologous proteins, but also a cysteine located down-stream of this motif (position 61), was found to be essential for the activity of the R. meliloti FdxN protein. Changing the amino acid residue proline in position 56 into methionine resulted in a FdxN mutant protein with decreased activity, whereas changes in positions 35 (Asp35Glu) and 45 (Gly45Glu) had no significant effect on the function of the FdxN mutant proteins. In contrast to bacterial-type ferredoxins, which contain two identical cysteine motifs of the form C-X2-C-X2-C-X3-C, nif-associated ferredoxins, including R. meliloti FdxN, are characterized by two different cysteine motifs. Six "additional" amino acids separate the second (Cys42) and the third cysteine (Cys51) in the C-terminal motif (C-X2-C-X8-C-X3-C).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603076 TI - Processing by OmpT of fusion proteins carrying the HlyA transport signal during secretion by the Escherichia coli hemolysin transport system. AB - A fusion gene (ces-hlyAs) was constructed by ligating the genetic information for the C-terminal 60 amino acids (hlyAs) of Escherichia coli hemolysin (HlyA) to the ces gene for a cholesterol esterase/lipase (CE) from a Pseudomonas species. Part (about 30%) of the expressed fusion protein CE-HlyAs was secreted in E. coli carrying hlyB and hlyD genes. Following the insertion between the reporter gene and hlyAs of a linker sequence that contains the information for potential cleavage sites for the outer membrane protease OmpT, two different fusion proteins (PhoA-HlyAs and CE-HlyAs) were shown to be cleaved by OmpT between the two parts during HlyB/HlyD-mediated secretion. Processed PhoA and CE accumulated in the supernatant. The efficiency of cleavage by OmpT was considerably improved by increased ompT gene dose. It was further shown that OmpT preferentially recognizes potential cleavage sites within the linker sequence. PMID- 1603077 TI - Mutations in the DnaA binding sites of the replication origin of Escherichia coli. AB - Mutations (base changes) were introduced into the four DnaA binding sites (DnaA boxes) of the Escherichia coli replication origin, oriC. Mutations in a single DnaA box did not impair the ability of these origins to replicate in vivo and in vitro. A combination of mutations in two DnaA boxes, R1 and R4, resulted in slower growth of the oriC plasmid-bearing host cells. DnaA protein interaction with mutant and wild-type DnaA boxes was analyzed by DNase I footprinting. Binding of DnaA protein to a mutated DnaA box R1 was not affected by a mutation in DnaA box R4 and vice versa. Mutations in DnaA boxes R1 and R4 did not modify the ability of the DnaA protein to bind to other DnaA boxes in oriC. PMID- 1603078 TI - Glucose transport in the yeast Kluyveromyces lactis. I. Properties of an inducible low-affinity glucose transporter gene. AB - In most strains of Kluyveromyces lactis, respiratory function is not required for growth on glucose. However, some natural variant strains are unable to grow when respiration is blocked by specific inhibitors (Rag- phenotype). This phenotype is due to an allelic variation of the chromosomal gene RAG1. The sensitive variants have a recessive allele rag1. The RAG1 gene has been cloned by complementation of a rag1 strain from a genomic bank derived from a Rag+ strain. The nucleotide sequence of the cloned gene indicated that the RAG1 product was a sugar transporter protein. The amino acid sequence deduced from the gene structure contained the 12 hydrophobic segments typical of a transmembrane protein, and showed a high degree of homology with the GAL2 (galactose permease) and HXT2 (a high-affinity glucose transporter) proteins of Saccharomyces cerevisiae. In a rag1 null mutant, as in the natural rag1 variant, uptake of glucose at high external glucose concentrations was impaired. The RAG1 protein appears to correspond to a low-affinity glucose transporter. Transcription of the RAG1 gene, which was undetectable when cells were grown in glycerol, was induced by glucose. It is concluded that respiration-dependent growth on glucose of the Rag- variant strains is due to a defect in this inducible glucose transport system. PMID- 1603079 TI - Glucose transport in the yeast Kluyveromyces lactis. II. Transcriptional regulation of the glucose transporter gene RAG1. AB - The RAG1 gene encodes a membrane protein involved in the low-affinity glucose/fructose transport system of the yeast Kluyveromyces lactis. Analysis of steady-state mRNA levels analysis and quantitation of expression by beta galactosidase from RAG1-lacZ fusions assays revealed that the RAG1 gene was poorly expressed in cells grown under gluconeogenesis conditions, but was induced more than ten-fold when they were grown on various sugars. These sugars included glucose, fructose, mannose, sucrose, raffinose, as well as galactose. Nucleotide sequence and deletion analysis of the 5' flanking region of the RAG1 gene showed that an essential cis-acting element required for induced transcription of the RAG1 gene resided between -615 and -750 from the coding sequence. This region contained a 22 bp purine stretch, and a pair of 11 bp direct repeat sequences. The 11 bp repeats harbor a CCAAT motif, a consensus sequence for binding of the yeast and mammalian HAP2/3/4-type protein complex. The transcription of the RAG1 gene was dramatically affected by three unlinked mutations, rag4, rag5 and rag8. We discuss the possible roles of RAG4, RAG5 and RAG8 gene products in the expression of the RAG1 gene, as well as the importance of the inducible RAG1 gene in the fermentative growth of K. lactis. PMID- 1603080 TI - Characterization of the binding of transforming growth factor-beta 1, -beta 2, and -beta 3 to recombinant beta 1-latency-associated peptide. AB - Preprotransforming growth factor-beta 1 (TGF beta 1) is a 390-amino acid precursor polypeptide that undergoes a number of processing steps to yield mature TGF beta 1 (amino acid residues 279-390) and a pro portion (residues 30-278) termed beta 1-latency-associated peptide (beta 1LAP). The dimeric form of beta 1LAP has been shown to associate noncovalently with the mature growth factor, resulting in inactivation of biological activity. To further characterize this interaction, the mature TGF beta 1 was radioiodinated and used to determine dissociation constants. A cross-linking method using the bifunctional covalent cross-linker bis-(sulfosuccinimidyl)suberate was found to be the best approach for measuring the amount of bound growth factor. The efficiency of cross-linking was constant within each experiment and varied between 45-55%. Saturation plots and their associated Scatchard analyses indicate apparent Kd values between 1.1 1.8 nM. Competition of TGF beta 1 binding to beta 1LAP by TGF beta 2 and TGF beta 3 (two closely related growth factors) revealed that the latter also bind beta 1LAP tightly, with apparent Kd values of 1.9 and 0.4 nM, respectively. PMID- 1603081 TI - Pituitary-specific transcriptional initiation sites of the rat carboxypeptidase-H gene and the influence of thyroid hormone status. AB - Carboxypeptidase-H (CPH) is a metallocarboxypeptidase implicated in the processing of peptide hormones. Consistent with such a role, the gene for CPH is expressed in cells that secrete regulatory peptides, such as those of the brain and endocrine tissues. In the rat brain, CPH is transcribed from a single transcriptional start site associated with the initiator-type element first described in the gene encoding lymphocyte-specific terminal deoxynucleotidyltransferase. We have used a combination of Northern blot analysis and S1 nuclease protection mapping to describe the expression and transcription initiation pattern of the gene for CPH in the peripheral tissues and brain regions of the normal rat. The single transcriptional start site is used in all tissues examined, except the pituitary, where two additional specific initiation sites are found. The expression of the CPH gene is up-regulated in the anterior pituitary gland as a consequence of systemic thyroid hormone depletion, and this increase is associated with a preferential utilization of the novel upstream transcriptional initiation sites. Thus, the use of different major transcriptional initiation sites of the CPH gene in the pituitary gland is subject to differential direct or indirect thyroid hormone regulation. PMID- 1603082 TI - Tissue-specific expression of the rat insulin receptor-related receptor gene. AB - Characterization of genomic DNA encoding the insulin receptor-related receptor (IRR) previously revealed that the predicted IRR protein is closely related to the insulin and insulin-like growth factor-I receptor protein-tyrosine kinases. Using rat IRR genomic DNA as probe, IRR transcripts were detected by Northern blot analysis in RNA from rat kidney, stomach, and thymus, but not in RNA from other tissues, including skeletal muscle, brain, intestine, and uterus. Primer extension analysis using RNA from stomach revealed a single transcriptional start site 29 basepairs down-stream from a putative TATA box and 544 basepairs up stream of the initiator methionine codon. Amplification of IRR cDNA by polymerase chain reaction and isolation of partial IRR cDNA clones confirmed that the IRR gene is an expressed gene. PMID- 1603083 TI - Conditional transformation mediated via a pertussis toxin-sensitive receptor signalling pathway. AB - To determine whether a cloned receptor coupled to pertussis toxin (PTx)-sensitive G-proteins can induce cell proliferation and oncogenic transformation, as observed for receptors that elicit PTx-insensitive enhancement of phosphatidyl inositol (PI)-specific phospholipase-C (PLC) activity, nontransformed murine BALB/c-3T3 cells were transfected with the rat serotonin-1A (5-HT1A) receptor. The 5-HT1A receptor is coupled to PTx-sensitive G-proteins to induce a cell specific activation of PLC. While 1 microM 5-HT induced no change in PI turnover or cytosolic free calcium levels ([Ca2+]i) in receptor-negative nontransfected 3T3 cells, 5-HT induced a 2-fold increase in inositol trisphosphate accumulation and a 2.5-fold increase in [Ca2+]i in the 3T3-ZD8 clone, which expressed 0.6 +/- 0.2 pmol/mg protein of specific 5-HT1A binding sites. The stimulatory actions of 5-HT on PI turnover and [Ca2+]i in 3T3ZD8 cells displayed the pharmacology of the 5-HT1A receptor and were abolished by pretreatment with PTx. Thus, BALB/c-3T3 fibroblast cells express the PLC-linked pathway of the 5-HT1A receptor. Overnight treatment with 5-HT (1 microM) enhanced incorporation of [3H]thymidine into DNA extracted from serum-starved 3T3ZD-8 cells, an action that was also blocked by pretreatment with pertussis toxin. Long term (1-2 weeks) exposure to 5-HT in the medium led to phenotypic transformation of the cells, including the formation of foci with 1 microM 5-HT. These actions of 5-HT were not observed in untransformed 3T3 cells. We conclude that the PTx-sensitive PLC-linked pathway of the 5-HT1A receptor expressed in nontransformed BALB/c-3T3 cells, in concert with other serum-derived factors, predisposes the cells to enhanced proliferation and transformation. PMID- 1603084 TI - Activation of protein kinase-C differentially regulates insulin-like growth factor-I and basic fibroblast growth factor messenger RNA levels. AB - Fibroblasts represent one of the in vivo sites of insulin-like growth factor-I (IGF-I) production. In this study rat dermal fibroblasts in culture were used as a model system to assess the effect of activation of protein kinase-C on the levels of the mRNAs encoding IGF-I and another growth factor, basic fibroblast growth factor (bFGF). IGF-I and bFGF mRNA levels were determined using a solution hybridization/RNase protection assay. Treatment of cells in serum-free medium containing 0.25% BSA (MEM + BSA) with the tumor-promoting phorbol ester phorbol 12-myristate 13-acetate (PMA) decreased IGF-I and increased bFGF mRNA levels in a time- and dose-dependent fashion. The peak effect of 100 nM PMA on IGF-I mRNA levels occurred at 9 h, whereas the peak effect on bFGF mRNA levels occurred after 3 h of incubation. In dose-response studies, half-maximal inhibition of IGF I mRNA levels was achieved with approximately 0.08 nM PMA, while half-maximal stimulation of bFGF mRNA levels was achieved with approximately 3 nM PMA. Inhibition of protein synthesis with cycloheximide abrogated the effect of PMA on bFGF mRNA levels, but only partially inhibited the effect of PMA on IGF-I mRNA levels. Studies employing sphingosine or staurosporine to inhibit protein kinase C or preincubation in high doses of PMA to down-regulate protein kinase-C suggested that the effect of PMA on IGF-I and bFGF mRNA levels was mediated by activation of protein kinase-C, although both staurosporine and sphingosine had independent effects on the levels of these mRNAs and down-regulation of protein kinase-C had a sustained effect on IGF-I mRNA levels. Ligands known to activate protein kinase-C were then tested. Treatment of cells with 100 micrograms/ml of the synthetic diacylglycerol 1-oleoyl-2-acetyl-sn-glycerol decreased IGF-I mRNA levels to 25% and increased bFGF mRNA levels to 520% of the level present in cells maintained in MEM + BSA. Treatment of cells with thrombin or bradykinin also decreased IGF-I mRNA levels and increased bFGF mRNA levels, but whereas the effect of thrombin on IGF-I mRNA levels was marked, the effect of bradykinin was minimal, and whereas the effect of thrombin on bFGF mRNA levels was sustained, the effect of bradykinin was transient.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1603085 TI - Adrenergic regulation of the mitochondrial uncoupling protein gene in brown fat tumor cells. AB - A tumor appeared on the back of a transgenic mouse carrying the SV40 T-antigen under control of a mouse major urinary protein promoter. High levels of mRNA for the mitochondrial uncoupling protein (UCP) indicated that the tumor was a hibernoma. The tumor has been established as a transplantable tumor line in nude (nu/nu) mice and used as a source of cells to develop a tissue culture system for analyzing brown fat development and differentiation. Ucp expression in tumor cells cultured in Dulbecco's modified Eagle's medium and 10% fetal calf serum was virtually undetectable. Addition of 10(-7) M norepinephrine resulted in approximately a 30-fold induction of Ucp mRNA within 4 h. The induction by norepinephrine was independent of cell density and also independent of thyroid hormone and insulin during the first 5 days in culture. However, in order to maintain the inducibility of Ucp during prolonged culture periods, it was necessary to supplement the medium with insulin. In contrast to Ucp, the expression of Gdc-1, which encodes the cytoplasmic glycerol-3-phosphate dehydrogenase and which is also induced in brown fat by cold exposure, was repressed by norepinephrine and induced by the addition of insulin. Characterization of the adrenergic receptors required for Ucp induction with agonists and antagonists indicated that beta 1 receptors are predominantly utilized; there is no evidence for utilization of beta 3 and alpha 1 receptors for Ucp induction. PMID- 1603086 TI - Characterization of estrogen receptor variant mRNAs from human breast cancers. AB - The cDNAs for variant estrogen receptor (ER) mRNAs previously identified in human breast cancer biopsy samples have been cloned and characterized. Some of these cDNAs are unique to a tumor sample (e.g. clones 24 and 5), while others are present in multiple breast tumor samples (e.g. clone 4). The 5' ends of the variant cDNAs are essentially identical to sequences present in exons 1, 2, and 3 of the normal ER mRNA. However, at points which mark either the exon 2/intron or exon 3/intron boundaries, the variant cDNA sequences diverge and are unrelated to the normal ER mRNA. The unique sequences of clones 24 and 5 are unknown, and the unique sequence of clone 4 is related to the long interspersed repetitive LINE-1 sequences. The variant mRNAs contain open reading frames which could encode proteins containing known functional domains of the normal ER but missing others. In particular, the hormone binding domain of the normal ER is always missing. Furthermore, some of the variant transcripts may encode other unique proteins. In transient expression assays the proteins encoded by the variant ER mRNAs are unable to activate transcription of an estrogen-responsive reporter gene; neither are they able to modulate the ability of normal ER proteins to activate transcription. PMID- 1603087 TI - Extinction of prolactin gene expression in somatic cell hybrids is correlated with the repression of the pituitary-specific trans-activator GHF-1/Pit-1. AB - The tissue-specific expression of the PRL and GH genes is dependent on the presence of a pituitary-specific trans-activator, GHF-1/Pit-1. Previous studies indicate that somatic cell hybridization of rat pituitary GH3 cells with LB82 mouse fibroblasts frequently results in the extinction of GH and PRL expression. The extinction of the GH gene occurs at the transcriptional level, and is accompanied by repression of GHF-1/Pit-1 synthesis. To elucidate the mechanism of PRL extinction we further characterized these same somatic cell hybrid lines as well as the parental GH3 and LB82 cells. The pattern of PRL extinction and reexpression paralleled that of GH in the three hybrid lines that were examined. Two of these lines extinguished both GH and PRL synthesis, while a third displayed reexpression of both genes, apparently due to the loss of mouse chromosomal material. These studies revealed that the extinction of PRL expression in these hybrid lines occurs at the level of mRNA accumulation and is strongly correlated with the loss of GHF-1/Pit-1 mRNA and protein synthesis. These data suggest that in pituitary x fibroblast hybrids repression of the trans activator GHF-1/Pit-1 is a primary mechanism for the extinction of PRL and GH gene expression. PMID- 1603088 TI - Thyroid hormone receptor mediates transcriptional activation and repression of different promoters in vitro. AB - The thyroid hormone receptor (TR) has the dual ability to activate or repress transcription of specific genes. A cell-free transcription system was used to study the effects of TR on transcription by positively (TREpMLP) and negatively (TSH alpha) regulated promoters. Receptor-deficient HeLa cell extracts were complemented with baculovirus-produced TR. TR stimulated transcription from the TREpMLP promoter by 3-fold, and trans-activation did not require hormone. Transcriptional stimulation by TR required the presence of the TRE sequence and was diminished by the addition of competitor TRE binding sites. Baculovirus produced TR repressed transcription in vitro from the TSH alpha promoter by 30 50%, also in a hormone-independent manner. Transcription from a control adenovirus 2 major late promoter was unaffected by added TR. Receptor-specific antisera and competition with TRE binding sites impaired TR-mediated repression of the TSH alpha promoter. Unlike transcriptional stimulation, which was optimal when TR and HeLa extracts were added concomitantly, transcriptional repression by the TR was most effective when the receptor was preincubated with the alpha promoter, suggesting that receptor binding to the promoter may block access of other proteins to cause transcriptional repression. These results indicate that baculovirus-expressed TR mediates transcriptional activation and repression in a promoter-specific manner in vitro. This system provides a valuable model for examining transcriptional control by the TR. PMID- 1603089 TI - Internuclear migration of chicken progesterone receptor, but not simian virus-40 large tumor antigen, in transient heterokaryons. AB - The chicken progesterone receptor (PR) is a transcriptional regulatory protein that localizes predominantly within the nucleus of hormone-treated and untreated cells. Transient heterokaryons were generated between PR-expressing Cos-1 cells and PR-negative NIH3T3 cells to examine whether PRs are confined to the nucleus or are capable of bidirectionally traversing the nuclear envelope. Migration of PR from Cos-1 to NIH3T3 nuclei was observed in both the presence and absence of hormone. Since de novo PR synthesis was inhibited in heterokaryons with cycloheximide treatment, PRs that localize within NIH3T3 nuclei of heterokaryons must derive from preexisting receptors that were exported from Cos-1 nuclei. Thus, PR, like some nucleolar and heat shock proteins, appears to be capable of shuttling between the nuclear and cytoplasmic compartments. Not all proteins that enter the nucleus exhibit this trait, since simian virus-40 large tumor antigen, endogenously expressed in Cos-1 cells, does not efficiently translocate to NIH3T3 nuclei of heterokaryons, which support internuclear migration of PR. Thus, proteins that may use analogous or identical mechanisms for nuclear import may differentially interact with the nuclear export machinery. Furthermore, the fact that PR and simian virus-40 large tumor antigen localization within nuclei is not identical, as revealed by laser scanning confocal microscopy, supports the notion that nuclear export may be influenced by subnuclear compartmentalization. PMID- 1603090 TI - Biphasic and synergistic activation of p44mapk (ERK1) by growth factors: correlation between late phase activation and mitogenicity. AB - We have examined the phosphorylation and protein kinase activity of p44 mitogen activated protein kinase (p44mapk) in growth factor-stimulated hamster fibroblasts using a specific antiserum. The activity of p44mapk was stimulated both by receptor tyrosine kinases and G protein-coupled receptors. Detailed kinetics revealed that alpha-thrombin induces a biphasic activation of p44mapk in CCL39 cells: a rapid phase appearing at 5-10 min was followed by a late and sustained phase still elevated after 4 h. Inactivation of alpha-thrombin with hirudin after 30 sec, which prevented DNA synthesis, did not alter the early p44mapk response but completely abolished the late phase. Pretreatment of the cells with pertussis toxin, which inhibits by more than 95% alpha-thrombin induced mitogenicity, resulted in the complete loss of late phase activity, while the early peak was partially attenuated. Treatment of CCL39 cells with basic fibroblast growth factor also induced a strong activation of p44mapk. Serotonin, which is not a mitogen by its own, had no effect on late phase p44mapk activity, but synergized with basic fibroblast growth factor to induce late kinase response and DNA synthesis. Both early and late phase activation of p44mapk were accompanied by tyrosine phosphorylation of the enzyme. Together, the results indicate that there is a very close correlation between the ability of a growth factor to induce late and sustained p44mapk activation and its mitogenic potential. Therefore, we propose that sustained p44mapk activation is an obligatory event for growth factor-induced cell cycle progression. PMID- 1603091 TI - PCR based cloning and sequencing of isogenes encoding the tree pollen major allergen Car b I from Carpinus betulus, hornbeam. AB - Cloning of the gene encoding the major allergen, Car b I, from Carpinus betulus (hornbeam) pollen was performed using the Polymerase Chain Reaction (PCR) to specifically amplify the gene of interest using single stranded cDNA as template. Specific primers, deduced from the aminoterminal sequence of the purified protein, were tailored to facilitate direct expression of plasmic clones, and the large fraction of positive clones obtained, revealed the presence of isogenic variation. Three clones were characterized in detail by antibody based assays and nucleotide sequencing. The recombinant allergens were shown by crossed immunoelectrophoresis (CIE) to precipitate with monospecific polyclonal rabbit antibodies raised against purified Bet v I, by crossed radioimmunoelectrophoresis (CRIE) to bind tree pollen allergic patient serum IgE, and by immunoblotting to bind murine monoclonal antibodies, raised against purified Car b I from pollen. Car b I is encoded by a 159-triplets open reading frame. The molecular masses (M(r) = 17272, 17355 and 17217 Da, respectively), the amino acid composition, and the aminoterminal sequence of the predicted polypeptides agree well with data obtained by analysis of the protein purified from pollen. The deduced amino acid sequences show pronounced homology (73, 75 and 74% identities respectively) to Bet v I, the major allergen from Betula verrucosa (white birch) pollen. Soluble recombinant Car b I, without a fusion partner, was produced in Escherichia coli with an immunochemical reactivity closely resembling that of the native pollen allergen. The tree pollen major allergens therefore constitute an ideal system for the study of allergenic epitopes. PMID- 1603092 TI - Sulfonyl fluoride serine protease inhibitors inactivate RNK-16 lymphocyte granule proteases and reduce lysis by granule extracts and perforin. AB - Cytolytic granules purified from natural killer lymphocytes (NK) contain a pore forming protein (perforin) and a number of serine proteases. When these proteases are inhibited by serine protease-specific isocoumarin reagents the serine proteases are inactivated and the cytolytic activity of the granules is decreased. Paradoxically, it has been found that the general serine protease inhibitor phenylmethylsulfonyl fluoride (PMSF) frequently cannot block killing even though it inhibits many of the serine proteases. At the same time it has been reported that "purified" perforin alone can lyze cells. To address these inconsistencies we first compared the ability of PMSF and four new sulfonyl fluoride serine protease inhibitors to inhibit proteases and cell lysis. We determined the effects on lysis and the second order inhibition rate constants for five granule protease activities: ly-tryptase, ly-chymase, Met-ase (methionine cleaving), Ser-ase (serine cleaving) and Asp-ase (aspartic acid cleaving). One compound, 2-(Z-NH(CH2)2CONH)C6SO2F, was a potent inhibitor of Met ase activity (k(obsd)/[I] = 162 M-1 s-1), ly-chymase activity (k(obsd)/[I] = 147 M-1 s-1), and granule-mediated as well as perforin-mediated lysis. PMSF was a poor inhibitor of granule proteases (k(obsd)/[I]'s less than 7 M-1 s-1 for four activities and no inhibition of Ser-ase); the lack of reactivity is consistent with the failure of PMSF to block granule lytic activity. We also prepared enriched perforin by anion exchange chromatography and showed that a ly-chymase and a Met-ase associated with perforin. By inhibiting these proteases we also inhibited lytic activity. PMID- 1603094 TI - Microheterogeneity of a purified IgG1 due to asymmetric Fab glycosylation. AB - A murine monoclonal anti-granulocyte IgG1, IMMU-MN3, was seen to exhibit heterogeneity. On reduced SDS-PAGE, the purified antibody appeared as two heavy chain bands of unequal intensity, and only one light-chain band. Hydrophobic interaction chromatography (HIC) also resolved two populations of the IMMU-MN3 antibody. Based on Concanavalin A affinity chromatography, enzymatic digestion with Endoglycosidase F and carbohydrate analysis, it was found that the heterogeneity detected by SDS-PAGE and HIC was due to differences in glycosylation. Furthermore, sequential gel analysis (non-reduced/reduced) demonstrated that the upper heavy-chain band was asymmetrically glycosylated. PMID- 1603093 TI - Characterization of a new subgroup of human Ig V lambda cDNA clone and its expression. AB - From a human bone marrow cDNA library, we have cloned and sequenced a gene which cross-hybridized with murine pre-B cell-specific gene 8HS-20 cDNA under the low stringent condition. Sequence analysis predicted that this gene (YM-1) encoded 240 amino acids which had the basic structure of immunoglobulin lambda light chain. The 3' half of the YM-1 sequence was identical to the J lambda 2 C lambda 2 region except for four nucleotides. The 5' part of the gene had 87.6% sequence homology with the reported V lambda gene called T1. Comparison of the deduced amino acid sequences with representative members of the seven other V lambda subgroups showed considerable structural homology, but the maximum homology with these chains was 44%. Therefore, we conclude that YM-1 belongs to a new V lambda subgroup. Interestingly YM-1 showed higher homology with VpreB1 (56%) than with any of the other V lambda subgroups. By Southern blot analysis four to six cross hybridizing V lambda bands were detected at high stringency. Expression of the V lambda gene was observed in immature as well as mature B cell lines without accompanying V-JC gene joining, suggesting that V lambda of the YM-1 locus is activated at the early stage of maturation. PMID- 1603095 TI - Complement membrane attack complexes induce in human leukemic cells rapid expression of large proteins (L-CIP). AB - The effect of sublytic doses of the complement membrane attack complexes (MAC) on protein synthesis in human leukemic cells was examined. As shown herein, rapid protein synthesis is evident in K562 erythroleukemic cells upon exposure to sublytic complement doses. Analysis of cell extracts by SDS-PAGE revealed high molecular weight proteins which appeared in the cells already after 15 min treatment with complement at 37 degrees C, reaching a maximal level after 40-50 min. These large complement-induced proteins (L-CIP) were clearly observed in gels stained by Coomassie blue and in autoradiograms following [35S]-Met or [3H] Leu incorporation. Rabbit antibodies prepared against L-CIP were reactive in immunoassays with extracts of MAC-treated cells but not of non treated cells. They also bound to the surface of intact K562 cells (as determined by immunofluorescence), but only after treatment of the cells with complement. Both heterologous (rabbit and guinea pig) and homologous (human) sera induced L-CIP synthesis. The induction of L-CIP was indeed mediated by the complement MAC since L-CIP could not be detected in K562 cells exposed to heat-inactivated human serum or C6-deficient rabbit serum. Similarly, C7- or C8-deficient human sera could not induce L-CIP production unless they were reconstituted with purified human C7 or C8, respectively. The synthesis of L-CIP was largely inhibited by the protein synthesis inhibitors cycloheximide and puromycin and partially inhibited by the RNA synthesis inhibitor actinomycin D. L-CIP was similarly induced in two other human leukemic cell lines, U937 and HL-60, but not in K562/S, a subline of K562 which is highly sensitive to complement damage. These results are discussed with respect to the resistance of leukemic cells, and nucleated cells in general, to complement-mediated immune damage. PMID- 1603096 TI - Analysis of antigenicity and immunogenicity of five different chemically defined constructs of a peptide. AB - The aim of this study was to compare the antigenicity and the immunogenicity of five constructs of a peptide, including the peptide in single copy, a tandem repeat containing three copies, a copolymer with glutaraldehyde and two constructs based on the MAP (Multiple Antigenic Peptide) model, one containing two copies (MAP-2) and the other, eight copies of the peptide (MAP-8). The peptide used in this test was the 115-131 sequence derived from the rSm28-GST antigen of Schistosoma mansoni. All constructs were recognized by rSm28-GST specific antibodies in solid phase immunoassays. However, the binding was higher when the MAP-8 was used as antigen at least partly because of its better coating on the microtiter plates. In vitro lymphoproliferative assays showed that polymer was mitogenic, repeat and MAP-2 did not stimulate rSm28-GST specific T cells while MAP-8 induced a slight response. The injection of MAP-8 to rats led to important antibody and T cell responses higher than those obtained with the other constructs. The IgG2a (cytotoxic antibody in schistosomiasis)/IgG2c (blocking antibody) ratio was independent of the immunogen. Taken together these results demonstrate that both the antigenicity and the immunogenicity of a peptide containing T and B cell epitope(s) are strongly related to the molecular form whereby it is presented and that the MAP-8 construct can be useful in serodiagnosis or in vaccination trials using synthetic peptides. PMID- 1603097 TI - A defect in the humoral immune response to protein antigens and haptens in immunoglobulin mu heavy-chain transgenic mice. AB - We have examined the antibody response in mice expressing a functionally rearranged mu Ig heavy chain derived from a hybridoma antibody with specificity for the hapten 4-hydroxy-3-nitrophenyl (NP). Transgenic mice and their normal littermates were immunized with the antigens NP-OVA, the synthetic polypeptide (Tyr,Glu)-Ala-Lys ((T,G)-A-L), or saline. The presence of serum antibodies to NP BSA, OVA, (T,G)-A-L, and BSA was examined by ELISA. Sera were evaluated prior to immunization and at periods of up to 4 months following immunization. Prior to immunization, transgenic mice had high levels of IgM anti-NP antibody but no detectable antibody to the other antigens. Both the primary and secondary antibody responses of transgenic mice to NP, OVA, and (T,G)-A-L were depressed when compared with the response of non-transgenic mice. Because of reports that these transgenic mice have increased proportions of CD5 + B-cells, a subpopulation associated with the production of autoantibodies, we examined these mice for the production of both IgG and IgM rheumatoid factors and anti-DNA antibodies. Transgenic mice had a modest increase in the spontaneous production of IgM anti-DNA. These data demonstrate a functional defect in the humoral immune response of mu transgenic mice. PMID- 1603098 TI - [Allergic rhinoconjunctivitis--past and present aspects]. AB - Allergic rhinoconjunctivitis can be divided into two forms: a seasonal one (pollen-induced) and a perennial one (e.g. provoked by house dust mites). There is still a tendency for underdiagnosing the disease, especially concerning the perennial form. Besides the typical diagnostic procedures, measurement of mediators in the nasal lavage are used for scientific research as well as for clinical reasons nowadays. The clinical picture is described with the terms "sneezer", "blower" and "blocker". During an acute phase of the disease the patients feel generally sick--due to the immunological inflammation. The new nonsedating oral antihistamines are the first choice for the saisonal form, whereas topical steroids are the "gold standard" for the perennial form. Guidelines for therapy are discussed. PMID- 1603099 TI - [Hinman syndrome. Pronounced renal failure as a sequela of pseudo-neurogenic disorder of bladder emptying]. AB - The case of an eight year old girl is presented who was seen because of secondary enuresis and recurrent urinary tract infection. Detailed examinations revealed urinary retention and sustained renal insufficiency (Creatinine clearance: 11 ml/min x 1.73 m2) due to a pseudo-neurogenic bladder. After improvement of renal function by continuous bladder drainage, bladder dysfunction was successfully treated by medication (Phenoxybenzamine, Baclofen), conventional physical therapy and biofeedback. PMID- 1603101 TI - [Martin-Bell syndrome. Improved possibilities for molecular genetic diagnosis]. AB - In a former molecular segregation analysis of fra x mental retardation in 27 families at risk we had used marker gene probes with a relatively high recombination fraction. Thus, the resulting risk for a false diagnosis was comparatively high. To diminish this risk, all families were reanalyzed with the newly invented and more closely linked gene probes RN1A, VK23B, VK21C and U6.2. Using these probes as molecular markers we performed Southern hybridization experiments. The remaining diagnostic risk due to recombination events could be reduced to 2% up to 20% compared to preanalysis. The portion of informative families (91%) is in good agreement with the expected cumulative heterozygosis frequency of 93.4% for all 4 markers investigated. This high frequency and the very low remaining risk for a false diagnosis therefore enable a far more precise molecular diagnostic of the Martin-Bell-syndrome. PMID- 1603100 TI - [Unilateral renal artery stenosis. Color-coded Doppler sonography and captopril scintigraphy in a 13-year-old patient]. AB - Modern noninvasive techniques, such as doppler sonography or color-encoded doppler sonography, have only rarely been used for diagnosis of renovascular hypertension in children. In the following case report, we describe the successful diagnosis of renovascular hypertension in a 13-year-old girl by using color-encoded doppler sonography and Captopril renal scintigraphy. The patient was admitted with hypertension of 180/130 mmHg. Laboratory findings showed elevated plasma renin and aldosterone concentrations. No abnormalities were found by abdominal sonography, isotope renography, intravenous pyelography, or in venous digital subtraction angiography. However, subsequent color-encoded doppler sonography clearly showed evidence of an artery stenosis of the right kidney. Furthermore, isotope renography one hour after oral administration of captopril revealed an almost complete loss of glomerular filtration rate of the right kidney. Based on these findings, arterial digital subtraction angiography, including transluminal angioplasty, was performed. During this treatment procedure, the right renal artery stenosis could be confirmed and was subsequently dilated without complication. In the following twelve months the patient remained normotensive and required no further antihypertensive drug treatment. PMID- 1603103 TI - [Protective clothing and face masks in the pediatric clinic: necessary or a ritual?]. PMID- 1603102 TI - [Physiologic blood coagulation studies in idiopathic arterial thrombosis]. AB - QUESTIONING: The prevalence of inherited thrombotic syndromes in the general population appears to be higher than that of inherited bleeding disorders. However, the most important candidates for screening are patients with unexplained thromboembolism at ages of less than 40 years: In 19 children suffering from "idiopathic" arterial thrombosis laboratory screening has been performed. METHODS: PT, PTT, TT, platelet count, spontaneous platelet aggregation, von Willebrand-factor, fibrinogen, plasminogen, antithrombin III, protein C, C1-inactivator, alpha-1-antitrypsin, alpha-1-antichymotrypsin, alpha-2 antiplasmin and alpha-2-macroglobulin have been investigated. RESULTS: Compared to an age matched healthy control group we could demonstrate in children with arterial thrombosis in vitro platelet activation with significant enhanced platelet aggregation, elevated levels of von Willebrand-factor and alpha-1 antichymotrypsin at the onset of disease. Protein C and alpha-2-antiplasmin were significantly decreased. These changes turned back to normal in the following 6 to 9 months. PT, PTT, TT, platelet count, plasminogen, alpha-1-antitrypsin, c1 inactivator and alpha-2-macroglobulin showed no alterations compared to controls. CONCLUSIONS: Platelet activation and alteration of platelet function have been shown in vivo and in vitro to initiate thrombosis. The von Willebrand's VIII molecule is involved in this step. The lowering of protein C levels at the onset of thrombotic diseases is discussed to be due to an increased turnover, whereas the decreased levels of alpha-2-antiplasmin might be a counter-regulation to the thrombotic event, showing an "activated" fibrinolytic system. PMID- 1603104 TI - [The oneiroid experience. On the presentation and psychopathology of the experience of fictional realities]. PMID- 1603105 TI - Modern management of malignant melanoma. PMID- 1603106 TI - Differential diagnosis of pigmented lesions of the skin. PMID- 1603107 TI - Histopathologic features of malignant melanoma and other pigmented lesions of the skin. PMID- 1603108 TI - The practitioner's approach to management of an atypical mole. PMID- 1603109 TI - Monoclonal antibody immunoconjugates in the diagnosis and treatment of advanced melanoma. AB - It appears that monoclonal antibody immunoconjugates may have a role in the radioimmunodiagnosis of melanoma. The precise method of administering the immunoconjugate still remains to be defined. Also evident is the possibility of treating patients with metastatic melanoma with repeated doses of a monoclonal antibody ricin A-chain immunotoxin, but appropriate dosing schedules of the immunotoxin need to be explored further. The agents selected for suppressing the immune response need further study. PMID- 1603110 TI - Radiological considerations in diagnosis of metastatic melanoma. PMID- 1603111 TI - Surgical treatment of melanoma: what is controversial and what is not? PMID- 1603112 TI - Role of radiotherapy in malignant melanoma. PMID- 1603113 TI - Humoral antimelanoma immunity: induction by mouse antiidiotypic mAb, MK2-23 and association with survival of patients with advanced melanoma. AB - This study has shown that a mouse antiidiotypic mAb bearing a mirror image of HMW MAA can break tolerance to a well-defined self HMW-MAA and can induce humoral anti HMW-MAA immunity in patients with melanoma. Furthermore, the induction of an immune response to a well-defined melanoma-associated antigen has been shown to be associated with a favorable clinical response. If this association reflects a cause-effect relationship between the two parameters, the anti HMW-MAA immunity induced by mouse antiidiotypic mAb MK2-23 may effect immune destruction of melanoma cells and may interfere with the metastatic potential of those cells because of the suggested role of HMW-MAA in this phenomenon. PMID- 1603114 TI - Immunotherapy of metastatic melanoma with interleukin-2. PMID- 1603115 TI - Primary care for patients with HIV. AB - AIDS will soon emerge as one of the top five causes of death in the United States. By 1995 it is going to be roughly equivalent to stroke in this regard: about 200,000 deaths annually. By that year between 400,000 and 500,000 AIDS cases will have been reported in this country. Right now our health care system, which is so sophisticated but which can be so inadequate, is effectively addressing AIDS in some areas of the country but is not effectively addressing the HIV epidemic. In order to identify HIV infection early, we all have to be involved. As internists we have to routinely offer screening. We have to make it easily accessible to our patients. There should be no more thought of ignoring the question of HIV infection than of ignoring smoking. There is no other answer to this major public health dilemma, and despite all the AIDS centers that are developing and the funding for in-patient and out-patient facilities, I think they are all going to be overwhelmed eventually, particularly in New York City, if we do not develop a more broad-based approach to the problem. PMID- 1603116 TI - Pulmonary complications of HIV infection. PMID- 1603117 TI - HIV infection: the dominant new face of tuberculosis. PMID- 1603118 TI - Endothelial dysfunction in pulmonary hypertension. PMID- 1603119 TI - Calcium intake and peak bone mass. PMID- 1603120 TI - Hand-washing and nosocomial infections. PMID- 1603121 TI - The polygraph test--a flawed diagnostic method. PMID- 1603122 TI - Anesthesia in neonatal cardiac surgery. PMID- 1603123 TI - Anesthesia in neonatal cardiac surgery. PMID- 1603124 TI - Anesthesia in neonatal cardiac surgery. PMID- 1603125 TI - Anesthesia in neonatal cardiac surgery. PMID- 1603126 TI - Anesthesia in neonatal cardiac surgery. PMID- 1603127 TI - Sinusitis in children. PMID- 1603128 TI - Ulcerated plaques in the aortic arch in patients with stroke. PMID- 1603129 TI - New light on secretory-component deficiency. PMID- 1603130 TI - Syncytial giant-cell hepatitis. PMID- 1603131 TI - Communicating with patients about their medications. PMID- 1603132 TI - Communicating with patients about their medications. PMID- 1603133 TI - Cigarette advertising in magazines and coverage of smoking hazards. PMID- 1603134 TI - Communicating with patients about their medications. PMID- 1603135 TI - Cigarette advertising in magazines and coverage of smoking hazards. PMID- 1603136 TI - One blue man with mucositis. PMID- 1603137 TI - Diagnosis and staging of colonic tumors by conventional abdominal sonography as compared with hydrocolonic sonography. AB - BACKGROUND: Ultrasonic examination has become increasingly important in the diagnosis of diseases of the gastrointestinal tract. In neoplastic diseases of the large intestine, however, the diagnostic value of conventional transabdominal sonography is limited. The purpose of this investigation was to determine whether the evaluation and staging of colonic tumors would be improved by the retrograde instillation of water into the colon in a procedure called hydrocolonic sonography. METHODS: Three hundred patients were examined in a prospective study in which both conventional transabdominal sonography and transabdominal hydrocolonic sonography were performed before the diagnosis was verified by colonoscopy. The indication for the examinations was abdominal pain, diarrhea, weight loss, or the presence of occult blood in a stool specimen. RESULTS: With the instillation of water into the colon, it was possible to display the colon sonographically from the rectosigmoid transition to the cecum in 97 percent of the patients examined. In addition to permitting the evaluation of the colonic lumen, the procedure allowed the five layers of the colonic wall and the connective tissue surrounding the colon to be examined in detail. Only 9 of 29 carcinomas were diagnosed by conventional abdominal sonography (31 percent), whereas hydrocolonic sonography permitted the diagnosis of 28 (97 percent). No polyps could be detected by conventional abdominal sonography, whereas hydrocolonic sonography permitted the diagnosis of 38 of 42 polyps greater than or equal to 7 mm (91 percent) and 3 of 12 polyps less than 7 mm (25 percent). In addition, detailed evaluation of the structure of the bowel wall with hydrocolonic sonography permitted a more precise staging of colonic tumors. CONCLUSIONS: Hydrocolonic sonography, a new diagnostic procedure, can facilitate the diagnosis and staging of colonic tumors. PMID- 1603138 TI - An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. AB - BACKGROUND: Constriction of small pulmonary arteries and arterioles and focal vascular injury are features of pulmonary hypertension. Because thromboxane A2 is both a vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of pulmonary hypertension. Its effects are antagonized by prostacyclin, which is released by vascular endothelial cells. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in pulmonary hypertension, reflecting platelet activation and an abnormal response of the pulmonary vascular endothelium. METHODS: We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 20 patients with primary pulmonary hypertension, 14 with secondary pulmonary hypertension, 9 with severe chronic obstructive pulmonary disease (COPD) but no clinical evidence of pulmonary hypertension, and 23 normal controls. RESULTS: The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in patients with primary pulmonary hypertension and patients with secondary pulmonary hypertension, as compared with normal controls (3224 +/- 482, 5392 +/- 1640, and 1145 +/- 221 pg per milligram of creatinine, respectively; P less than 0.05), whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased (369 +/- 106, 304 +/ 76, and 644 +/- 124 pg per milligram of creatinine, respectively; P less than 0.05). The rate of excretion of all metabolites in the patients with COPD but no clinical evidence of pulmonary hypertension was similar to that in the normal controls. CONCLUSIONS: An increase in the release of the vasoconstrictor thromboxane A2, suggesting the activation of platelets, occurs in both the primary and secondary forms of pulmonary hypertension. By contrast, the release of prostacyclin is depressed in these patients. Whether the imbalance in the release of these mediators is a cause or a result of pulmonary hypertension is unknown, but it may play a part in the development and maintenance of both forms of the disorder. PMID- 1603139 TI - The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. AB - BACKGROUND: Primary pulmonary hypertension is a progressive, fatal disease of unknown cause. Vasodilator drugs have been used as a treatment, but their efficacy is uncertain. METHODS: We treated 64 patients with primary pulmonary hypertension with high doses of calcium-channel blockers. Patients who responded to treatment (defined as those whose pulmonary-artery pressure and pulmonary vascular resistance immediately fell by more than 20 percent after challenge) were treated for up to five years. Their survival was compared with that of the patients who did not respond and with patients enrolled in the National Institutes of Health (NIH) Registry on Primary Pulmonary Hypertension. Warfarin was given to 55 percent of the patients as concurrent therapy, on the basis of a lung scan showing nonuniformity of pulmonary blood flow (47 percent of patients who responded and 57 percent of those who did not respond). RESULTS: Seventeen patients (26 percent) responded to treatment, as indicated by a 39 percent fall in pulmonary-artery pressure and a 53 percent fall in the pulmonary-vascular resistance index (P less than 0.001). Nifedipine (mean [+/- SD] daily dose, 172 +/- 41 mg) was given to 13 patients, and diltiazem (mean daily dose, 720 +/- 208 mg) was given to 4 patients. After five years, 94 percent of the patients who responded (16 of 17) were alive, as compared with 55 percent of the patients who did not respond (26 of 47, P = 0.003). The survival of the patients who responded was also significantly better than that of the NIH registry cohort (P = 0.002) and patients from the NIH registry who were treated at the University of Illinois (P = 0.001). The use of warfarin was associated with improved survival (P = 0.025), particularly in the patients who did not respond. CONCLUSIONS: This study suggests that high doses of calcium-channel blockers in patients with primary pulmonary hypertension who respond with reductions in pulmonary-artery pressure and pulmonary vascular resistance may improve survival over a five-year period. PMID- 1603140 TI - Calcium supplementation and increases in bone mineral density in children. AB - BACKGROUND: Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. METHODS: We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). RESULTS: The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. CONCLUSIONS: In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced. PMID- 1603141 TI - Thyrotoxicosis and the heart. AB - Many patients with thyrotoxicosis have clinical features that reflect the effects of excess thyroid hormone on the cardiovascular system. Thyrotoxicosis can aggravate preexisting cardiac disease and can also lead to atrial fibrillation, congestive heart failure, or worsening of angina pectoris. In elderly patients, these cardiac manifestations may dominate the clinical picture and warrant the measurement of the serum thyrotropin concentration. In the absence of preexisting cardiac disease, treatment of thyrotoxicosis usually results in a return of normal cardiac function. PMID- 1603142 TI - [Skin cancer following long-term photochemotherapy]. PMID- 1603143 TI - [Contraception in young subjects]. PMID- 1603144 TI - [Endothelins]. PMID- 1603145 TI - [Experiences in the treatment of intestinal invagination in children]. AB - Intussusception is one of the more common causes of an acute abdomen in infancy. There is discussion about the appropriate method of treatment, and especially about the criteria for hydrostatic reduction. To evaluate the effectiveness of treatment of patients with intussusception presenting at the Paediatric Surgical Centre in Amsterdam, a retrospective study was carried out. 84 Cases were seen between 1980-1990. Three quarters of the children were operated, one-third without prior barium enema. In half the cases an attempt at hydrostatic reduction was made, and this succeeded in only 43%. Ultrasound was only rarely used diagnostically. The literature shows that the use of air to attempt reduction is more likely to be effective and less likely to cause complications than barium. PMID- 1603146 TI - [Simple ligation superior to inversion of the appendiceal stump; a prospective randomized study]. AB - OBJECTIVE: To compare two methods of treatment of the appendix stump after appendectomy for acute appendicitis. DESIGN: A prospective randomised trial of 134 consecutive appendectomies in which the appendix stump was either simply ligated or ligated and doubly invaginated. SETTING: Department of General Surgery, St Joseph Hospital, Veldhoven, the Netherlands. PATIENTS AND METHODS: During a period of 15 months all patients in whom an appendectomy for acute appendicitis was performed were allocated at random to the two groups. The following data were recorded: age, sex, histological diagnosis, hospital stay and occurrence of complications. All patients were followed until 6 months after the operation. The data were analysed statistically with the chi-square-test and the Mann-Whitney test. P less than 0.05 was considered significant. RESULTS: The appendix stump was ligated in 79 patients and invaginated in 55. Both groups were similar with respect to age, sex, degree of appendiceal inflammation, antibiotic treatment and hospital stay. There were significantly more wound infections in the 'invagination' group (p = 0.017). The other complications showed no statistical intergroup difference. CONCLUSION: Simple ligation facilitates and shortens appendectomy. It is a safe procedure, preventing deformation of the caecal wall and possibly reducing the risk of postoperative ileus due to adhesions. We therefore recommend simple ligation as the standard procedure at appendectomy. PMID- 1603147 TI - [The importance of HDL-cholesterol level determination in the classification of persons at increased risk of coronary heart disease]. AB - The evidence is growing that not only total cholesterol, but also HDL cholesterol is an important predictor of coronary heart disease. In the Framingham Study, the total cholesterol/HDL cholesterol ratio gave the best prediction for the coronary heart disease risk. With data of the Netherlands Monitoring Risk Factor Project it was investigated to what extent persons with a high ratio (greater than or equal to 7) were identified when the criteria of the Netherlands Cholesterol Consensus were applied. Between 1987 and 1989 total and HDL cholesterol were determined in about 22,000 men and women aged 20-59. Twenty per cent of the men had hypercholesterolaemia (total cholesterol greater than or equal to 6.5 mmol/l). Of the hypercholesterolaemic men, 60 per cent did not have a high total/HDL cholesterol ratio. Eighteen per cent of the women were hypercholesterolaemic. Of all hypercholesterolaemic women, 80 per cent did not have a high total/HDL cholesterol ratio. Therefore, it is important that after a first screening on total cholesterol, HDL cholesterol is measured at the second cholesterol determination. Subsequently, a decision about treatment should be made, based on the total/HDL cholesterol ratio and the presence of other risk factors (hypertension, smoking, obesity, diabetes and a family history of cardiovascular disease. PMID- 1603148 TI - [Blunt thoracic trauma with lesions of the heart and large vessels]. AB - A man aged 26 was admitted after a traffic accident. The chest X-ray showed widening of the mediastinum without rib or sternal fractures. Therefore an aortogram was made which showed an avulsion of the aortic valve and a rupture of the left common carotid artery. The aortic valve was repaired by suturing and the carotid artery reimplanted into the left subclavian artery. Blunt chest trauma is becoming more common. If there is widening of the mediastinum on the chest X-ray an aortogram should be made. In this way the diagnosis, rupture of the thoracic aorta or of one of the aortic arch branches, and traumatic valve rupture can be made. Early diagnosis can be life saving. PMID- 1603149 TI - [2 complications of primary pulmonary tuberculosis in children]. PMID- 1603150 TI - [2 complications of primary pulmonary tuberculosis in children]. PMID- 1603151 TI - [2 complications of primary pulmonary tuberculosis in children]. PMID- 1603152 TI - [2 complications of primary pulmonary tuberculosis in children]. PMID- 1603153 TI - [Cytokines as immunotherapy in cancer]. PMID- 1603154 TI - [Medical activities under adverse conditions. The Directorate-General International Cooperation]. PMID- 1603155 TI - [Surgical treatment of cicatricial alopecia of the hairy scalp using tissue expansion]. PMID- 1603156 TI - [Carcinoid tumors; current viewpoints of biochemical and endocrine aspects, diagnosis and treatment]. PMID- 1603157 TI - [Aortic valve stenosis as cause of cardiac decompensation]. PMID- 1603158 TI - [Morbidity and mortality among Turkish subjects in The Netherlands]. PMID- 1603159 TI - [Immunotherapy in sepsis syndrome]. PMID- 1603160 TI - [Team work among physicians in resumption of work]. PMID- 1603161 TI - [Effectiveness of physiotherapy; a summary of 9 meta-analyses]. PMID- 1603162 TI - [A health survey and a survey of family physician house calls among Turkish and Dutch residents of Rotterdam]. AB - This paper reports the results of a study of the health situation of Turkish and autochthonous citizens of Rotterdam (Holland). A health interview survey was held with a random sample of 250 Turkish citizens (age 19-69) and a matched group of 250 autochthonous citizens. With ten percent of the respondents a second, in depth interview was held. With regard to (reported) presence of chronic diseases and to diseases in the two weeks preceding the interview no differences were found between Turkish and Dutch respondents. Turkish respondents answered less positively on questions that refer to subjective aspects of health. Turkish respondents consulted their general practitioner more frequently (RR = 2.62) and the dentist less frequently (RR = 0.61) than Dutch respondents. Little differences existed in frequency of visits to the medical specialist or in frequency of hospital admissions. With some caution, it may be concluded that the frequent visits to the general practitioner by Turkish respondents do not follow from differences in physical problems, but from cultural differences in the attitude towards the general practitioner. PMID- 1603163 TI - [9-year experience with continuous ambulatory peritoneal dialysis in one center]. AB - The experience gained with CAPD in a group of 101 patients with terminal renal failure and a subgroup of 19 patients with diabetes mellitus was analysed. The actuarial patient survival was 81% after two years and 50% after five years. The combined patient-technique survival after two years was 48.8%. The most important reasons for drop-out were transplantation (25%) and death (24%). Death was method related in 4 patients and caused by peritonitis in 2 of them. More often peritonitis was the cause of morbidity and temporary interruption (10 x) or of permanent abandoning of the method (11 x ). The peritonitis frequency during the whole period of nine years was 1 : 11.3 months. Use of the Y-connector Twinbag system and a U.V.-light system reduced the incidence substantially. However, faecal peritonitis remains a dangerous situation which cannot be prevented in this way. The mortality in patients with diabetes mellitus is high but not method related. The incidence of peritonitis is not significantly different from that among patients without diabetes mellitus. PMID- 1603164 TI - [Post-asphyctic encephalopathy of the neonate following administration of nalbuphine during childbirth]. AB - After an intramuscular injection of nalbuphine during parturition a foetal bradycardia of 30-40 beats/minute developed, which normalised after an intravenous maternal injection of naloxone. Because the cardiotocography did not show variability after the event, a caesarean section was performed. Six months later the child still had a severe neurological disorder which was attributed to intrauterine asphyxia. Several authors published reports in which no relevant clinical problems were described after nalbuphine given during labour. Recently, however, four children have been described with bradycardia and respiratory depression after maternal intravenous and/or intramuscular injection of nalbuphine. Apparently, the use of nalbuphine during labour can cause foetal bradycardia, both after intravenous and after intramuscular administration. Great reserve is advised regarding use of nalbuphine for this indication. The antidote naloxone should be within reach. PMID- 1603166 TI - [Clinical data and diagnosis of Yersinia enterocolitica infections; a retrospective study in Friesland]. PMID- 1603165 TI - [Morbidity and results of 100 radical hysterectomies performed in a oncological center]. PMID- 1603167 TI - [Eve's risk]. PMID- 1603168 TI - [Lead poisoning]. PMID- 1603169 TI - [Bladder carcinoma]. PMID- 1603170 TI - [Consultation between family physicians and specialists about the hospital admission of patients]. AB - Consultation between GPs and specialists about patients' in-hospital treatment is to be expected from the claim of Dutch GPs that they are responsible for continuous care for the patients on their lists. Data were gathered in the Dutch National Survey of General Practice: registration concerning all patients hospitalized during a three-month period (n = 7815) by 161 GPs. GPs consult specialists most frequently about the decision to admit patients (15% of all admissions). Consultation during patient's stay in hospital (5%) and about the discharge decision and possible aftercare (4%) is less usual. Consultation results from practical circumstances, such as the GP's initiative in the admission and a contact between patient and GP about the admission. The results leave GPs to answer the question whether the little actual consultation about the patient's stay in hospital, discharge and aftercare accords with their task to provide continuous care. PMID- 1603171 TI - [Agreement between specialists' care and family practitioner's intention in patient referral]. AB - The interaction between the general practitioner (GP) and the medical specialist during the referral process was studied in 309 referrals by GPs to medical specialists in eight hospitals in the north of the Netherlands, notably the extent of agreement between the specialist care and the intention of the GP. Furthermore the influence of two factors on the referral process was investigated: 'the clarity of the question in the referral letter' and 'the view of each other's professional tasks'. In most of the cases the GPs allowed the specialists a free hand. In the few cases the GP wanted a restricted consultation the specialist did more than the GP wanted him to do. In one of five referrals the GP or the specialist thought that the specialist had not done what the GP had asked. In most of these cases this impression was not confirmed by the objective evaluation by independent doctors. According to these the referral question was ambiguous. The GP's would like to have more influence on specialist care than the specialists were prepared to allow. The two factors each had an influence on several moments in the referral process. The main conclusion of the study is: the behaviour of the GP does not fit his attitude. PMID- 1603172 TI - [Estimate of the number of HIV-infected intravenous drug users in Amsterdam]. AB - By combining data collected through a cohort study among injecting drug users (IDUs), which started December 1985, with data on the number of notified cases of AIDS, the cumulative number of HIV-infected IDUs residing in Amsterdam was estimated. The estimated cumulative incidence of HIV-infection among IDUs in Amsterdam on 1 July 1991 was about 1050. By 1 July 1991 90 of these cases had been diagnosed with AIDS, while an estimated 150-200 cases died before AIDS had been diagnosed. The prevalence of IDUs residing in Amsterdam who were still alive and free of AIDS on 1 July 1991 was estimated to be about 750-800. Because of untimely deaths, only a limited number of these HIV-infected IDUs can be expected to be diagnosed with AIDS in the future. The prevalence on 1 July 1991 of HIV infected IDUs being alive and free of (diagnosed) AIDS and living elsewhere in the Netherlands is estimated at about 500. PMID- 1603173 TI - [Repeat estimate of the number of HIV-seropositive subjects in The Netherlands]. PMID- 1603174 TI - [Medical activities under adverse conditions. Working with the World Health Organization. Interview by J.M. Spanjer]. PMID- 1603175 TI - [Sterilization and legal proceedings]. PMID- 1603176 TI - [Which alternative material can be used in hypersensitivity reactions to (meth)acrylates?]. PMID- 1603177 TI - [Does rapid rising following coitus affect fertility?]. PMID- 1603178 TI - [Collusion ('neurotic zipper'); a special form of disturbed partner relationship]. PMID- 1603179 TI - What are you doing to prevent osteoporosis? PMID- 1603180 TI - NNA Nursing Shortage Task Force Report. PMID- 1603181 TI - Focus on ethics. The Patient Self Determination Act and Nebraska state law in practice. PMID- 1603182 TI - Breast health survey results. PMID- 1603183 TI - ANA Board of Directors adopts position statements on issues pertinent to HIV infection/AIDS. PMID- 1603184 TI - [Wilhelm Griesinger and community care]. AB - In Germany, the concept of community-based care with the aim of a far-reaching integration of mentally ill and disabled into society was already established by W. Griesinger in the last century. He proposed asylums, located in the cities and linked to general hospitals, for short-term treatment of the acute mentally ill. He pointed out that a short-term inpatient stay can only be achieved when hospital and natural support systems cooperate closely. He never assumed that all kinds of mental illnesses can be cured, but thought that most inpatients could be discharged from hospital even though some would be in need of sheltered living conditions. Today, W. Griesinger's proposals are accepted worldwide. In 1975, a German expert commission submitted a report utilizing Griesinger's ideas as indispensable components of a modern psychiatric care system. PMID- 1603185 TI - [Positive and negative symptoms of schizophrenia]. AB - Aim of the present study is to draw conclusions from published research regarding the positive-negative schizophrenia concept, and to try to present the opinion of supporters and critics of the concept in a balanced way. The historical background of the concept, from Reynolds and Jackson during the last century until today, is reviewed. After giving the definitions and presenting various instruments of evaluation, the question is discussed, how stable "negative" und "positive" psychopathological constellations are. Consideration of the results of research on the long-term time course of schizophrenia, as well as in genetics, biology und psychopharmacology, leads one to conclude, on the one hand that the positive-negative concept is relevant for clinical practice and research, but on the other hand that many of the present studies were not able to confirm a clear cut positive-negative dichotomy. PMID- 1603186 TI - [Duration of inpatient treatment of various psychiatric disease categories. A follow-up study]. AB - The frequency and duration of in-patient treatment in psychiatric and general hospitals was observed over an average 14-year period for 328 patients with different psychiatric diseases. Schizophrenics were more frequently admitted and spent longer in psychiatric institutions than all other diagnostic groups, but were admitted less frequently and for shorter periods to general hospitals. Patients suffering from organic mental illness and those with neurotic disorders had more frequent and longer periods of general hospital care. Drug dependent and neurotic patients were hospitalised more frequently and longer for psychiatric rather than for medical reasons in general hospitals. The total frequency and duration of psychiatric in-patient treatment was distinctly less frequent and of shorter duration for neurotic disorders as compared with schizophrenic or affective psychoses. PMID- 1603187 TI - [Transitional objects as regression phenomena in demented patients]. AB - Two demented patients, one with primary degenerative dementia and one with multi infarct dementia, each showed attachment to a soft toy animal, which fulfilled the criteria of a transitional object as described by Winnicott. This could be regarded as a regression phenomenon, according to the basic pathogenetic concept that cerebral disease causes a dissolution of the highest central nervous functions. PMID- 1603188 TI - [Psychogenic pain conditions. Defense structure and taxonomic subgroups]. AB - According to the results of the prospective Grant-Study the maturity of the individually available defence mechanisms has an essential influence on both physical and psychic well-being. Psychogenic pain patients are characterized by a "turning against self": an immature defense mechanism. By means of a cluster analysis, three taxonomic subgroups (types A, B, C) were defined. Type A is characterized by immature defense mechanisms (projection, turning against self and against object) and type C by neurotic defances (reaction formation and intellectualization), whereas type B manifests both intellectualization and a turning against self. Raised scores for anxiety, abnormal illness behaviour, depressive self-image, depressive mood and suicidal ideas are additional features which distinguish types A and B from type C. In contrast to type B, type A shows a negative social resonance, "doctor shopping" and drug abuse. The diagnostic differentiation of types A, B and C could be the basis of a differential indication to the different psychotherapeutic treatment approaches to chronic pain patients. PMID- 1603190 TI - [Biosocial relations as contact points in the social network. A contribution to the theoretical discussion in psychosomatic medicine]. AB - Psychosomatic medicine needs a theoretical model for clinical tasks and for research. To start from Freud's psychoanalytic theory (conversion and anxiety neurosis) and Alexander's model of the "vegative neurosis" a system theory concept of the bio-psychosocial model (Lipowski) is presented and discussed critically. Instead of further investigation on the problem of "unity", or on monistic or dualistic views of the mind-body problem, we propose a new theoretical approach. If we focus our interest on nodal points of the bio psychosocial network we can learn more about somatic-psychosocial interaction and can develop practical consequences for research and clinical issues. PMID- 1603189 TI - [Therapeutic approach to a case of simulated disorder with psychiatric symptoms]. AB - The case of a 38-year-old female inpatient with the diagnosis of factitious disorder with psychological symptoms--a presentation rarely reported in the psychiatric literature--is presented with special respect to her personality traits. On the basis of her biographical history a therapeutic approach was possible which tried to understand the symbolic value of the histrionic patient's symptoms. We regarded the manifestation of psychological symptoms as an attempt to express conflicts verbally and as an offer of a more mature form of communication in comparison to the former, autodestructive physical syndromes. PMID- 1603191 TI - [Psychotic episode caused by prevention of malaria with mefloquine. A case report]. AB - We report on a 41 year old woman, who after 750 mg mefloquine, a newer antimalarial agent, developed a psychosis with dizziness, confusion and delusions. The symptoms were more intensive and remained longer than hitherto reported in the literature. A total of 23 patients are known to have had psychiatric adverse effects under mefloquine. Psychotic episodes are undoubtedly though rarely associated with the intake of mefloquine. PMID- 1603192 TI - [Mianserin agranulocytosis followed by oxitriptan eosinophilia]. AB - A patient suffering from endogenous depression was treated with mianserin and developed agranulocytosis. After recovering from this, and with the depression in remission, the patient was given L-tryptophan. When this medication was removed from the market, due to the newly described eosinophilia-myalgia syndrome, a change was made to oxitriptan, which then caused a serious asymptomatic eosinophilia. No similar cases have yet been reported. Following withdrawal of oxitriptan, the eosinophilia disappeared. Evidence for any other cause of the condition was not found. Causes and physiopathology of drug-induced agranulocytosis and eosinophilia and the circumstances of such complications following use of mianserin and oxitriptan are discussed. PMID- 1603193 TI - [Electroconvulsive therapy in treatment of acute life threatening catatonia in toxic epidermal necrolysis (Lyell syndrome)]. AB - Toxic epidermal necrolysis (Lyell syndrome) developed in a 43-year woman treated with carbamazepine, perazine, and sulpiride for recurrent manic bipolar disorder. Five days after withdrawal of all psychotropic medication her psychiatric illness was exacerbated and a syndrome of lethal catatonia developed which was promptly treated with unilateral electroconvulsive therapy (ECT). Rapid remission of lethal catatonia after the first ECT treatment and of her affective disorder within days was achieved. According to clinical observations of the preneuroleptic era, early improvement of lethal catatonia following ECT may have been supported by concurrent high dose corticosteroid therapy for toxic epidermal necrolysis. PMID- 1603194 TI - [The bridge between basic research and clinical aspects. Comments on the contribution by H. Rommelspacher et al. Pathobiochemistry pharmacotherapy of alcohol withdrawal syndrome]. PMID- 1603195 TI - [Comments on the contribution by B. Funke, H. Reinecker and A. Commichau: Limits of cognitive training methods in long-term schizophrenic patients]. PMID- 1603197 TI - Special issue on Sjogren's syndrome. PMID- 1603196 TI - [Therapy in the borderline of psychiatry and neurology. Limassol, 21-23 February 1992]. PMID- 1603198 TI - Sjogren's syndrome in relation to other autoimmune diseases. AB - Autoimmune diseases can be divided into primary autoimmune diseases, in which the immune system is over-reactive, leading to an oligoclonal B cell stimulation, and secondary autoimmune diseases, in which the immune system is completely normal but some autoantigens are slightly altered, and are thus considered to be foreign. Sjogren's syndrome probably has characteristics of both types of autoimmune disease. The primary autoimmune diseases can be divided into organ specific autoimmune diseases like thyroiditis, gastritis and adrenalitis, and generalised autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis. Sjogren's syndrome has characteristics of both types of primary autoimmune disease, and therefore occupies a central position among the other autoimmune diseases. The focal position of the disease in the present issue of The Netherlands Journal of Medicine is because of the symposium organized for the occasion of the fifth anniversary of the "Dutch Association of Patients with Sjogren's Syndrome", of which this issue is the report. PMID- 1603199 TI - Morbus Sjogren, more than a dry syndrome. PMID- 1603200 TI - The diagnostic power of the tests for tear gland related keratoconjunctivitis sicca. AB - Laboratory tear function tests, such as the lactoferrin and the lysozyme test, reflect the level of tear gland deficiency and are, therefore, very useful for the clinician in the diagnosis of keratoconjunctivitis sicca (KCS). Although these tests do have an excellent discriminatory ability, they should be used in addition to clinical tests, such as the Schirmer-1 test, the tear film break-up time (BUT) and the Rose bengal (Rb) staining test. Schirmer's test, the most commonly used clinical test, measures tear fluid production. The tear film BUT, on the other hand, is the only test which establishes tear film instability. The Rose bengal score is strongly related to secondary damage of the superficial epithelium of the cornea and conjunctiva in patients with KCS. Thus, combining the results of these various tests facilitates the diagnosis of KCS and also the differentiation between Sjogren's KCS and non-Sjogren's KCS. PMID- 1603201 TI - Management of the oral features of Sjogren's syndrome. AB - In this paper the basis of the oral features of Sjogren's syndrome is described and guidelines for proper management of these features are given. The most pronounced oral symptoms are a dry sensation in the mouth and difficulties with swallowing and speech. Furthermore, these patients do not sleep well and may complain about burning mucous membranes, rampant caries and candidosis. Rampant caries can be prevented by optimal oral hygiene and frequent applications of a fluoride gel. Prophylaxis of candidosis can be achieved by meticulous oral hygiene and removal of predisposing factors (e.g. poorly fitting dentures). It is only possible to treat the other oral signs of Sjogren's syndrome symptomatically, because damage of salivary-gland parenchyma is progressive and irreversible. In the early stages of Sjogren's syndrome, good results can be obtained by gustatory or pharmacological stimulation of the salivary secretion. In the more advanced stages, the patient has to resort to oral rinses and saliva substitutes, the majority of which are not satisfactory. Promising results have been obtained with mucin-containing lozenges. PMID- 1603202 TI - Primary Sjogren's syndrome: clinical spectrum and mode of presentation based on an analysis of 50 patients selected from a department of rheumatology. AB - In this study we report on the clinical characteristics at the time of referral and during follow-up of 50 patients with primary Sjogren's syndrome (SS) in a rheumatological practice. The mean age of the patients at the time of diagnosis was 51.5 years. Four of them were men and 46 women. During a mean follow-up period of 9.1 yr (1-21 yr) from symptom onset the most common signs and symptoms were arthralgia (94%), complaints of dryness of the eyes (90%), mouth (82%) and skin (56%), weariness (64%), exanthema (48%), Raynaud's phenomenon (42%) and arthritis (42%). An elevated erythrocyte sedimentation rate (72%), elevated serum gammaglobulin (49%) and leucocytopenia (42%) were the most frequently encountered abnormalities of routine laboratory tests. After the initial hospital evaluation the diagnosis primary SS was made in only 10 (20%) of the patients. The diagnostic delay was on average 3.1 yr. Knowledge of the considerable heterogeneity of the disease may prevent extensive evaluations and provide better clinical care for patients with primary SS. PMID- 1603203 TI - Neuro-musculo-skeletal manifestations in primary Sjogren's syndrome. AB - Primary Sjogren's syndrome is a systemic autoimmune disorder whose main characteristics are dryness of the eyes and mouth, caused by lymphocytic infiltration of the exocrine glands. Patients may also show signs of extraglandular involvement of lung, liver, kidney and vessel walls, as well as of the central and peripheral nervous systems, muscles and joints. This article presents a review of the literature on extraglandular involvement of the peripheral and central nervous systems, muscles and joints. Several data support the hypothesis that vasculitis is the underlying mechanism. The need for an extended inventory of the extraglandular manifestations, preferentially linked to immunoserological and -histological investigations to gain more insight into the aetiology and pathogenesis is stressed. As far as the clinical picture is concerned, myalgia and arthralgia are often reported, but myositis and arthritis are rare. Data about the prevalence of peripheral and central nervous system involvement are conflicting: factors contributing to these differences are discussed. As insight into prognosis and therapy will strongly depend on the diagnostic criteria used, the need for international agreement on these is emphasized. PMID- 1603204 TI - Autoantibodies and their target antigens in Sjogren's syndrome. AB - The subject of this review is the humoral autoimmune response in Sjogren's syndrome. Autoantibodies in this disease are primarily directed against the Ro/SS A and La/SS-B autoantigens and against IgG (rheumatoid factor). The Ro/SS-A and La/SS-B autoantigens consist of a number of antigenic proteins coupled to small RNA molecules. These RNA-protein particles are present in all human cells and are strongly conserved throughout various species. Anti-Ro/SS-A and anti-La/SS-B autoantibodies can be detected using counter-immunoelectrophoresis, immunoblotting technique, ELISA or RNA precipitation assays. The preferred method of screening for anti-Ro/SS-A antibodies in human sera is counter immunoelectrophoresis; anti-La/SS-B antibodies are best detected with the immunoblotting technique. Anti-Ro/SS-A antibodies are found in 60% of patients with Sjogren's syndrome, but are not specific markers for this disease. Anti La/SS-B antibodies are present in approximately 40% of patients with Sjogren's syndrome; the only other disease where the antibody has been detected is systemic lupus erythematosus (15% positive). The origin and possible pathogenetic role of autoantibodies in Sjogren's syndrome is still unclear. Our view is that the current evidence supports a mechanism whereby autoantibodies are the product of an oligoclonal B-cell proliferation. The only instance where autoantibodies probably play a direct pathogenetic role is the occurrence of congenital heart block in the offspring of anti-Ro/SS-A and anti-La/SS-B positive mothers. PMID- 1603205 TI - Labial salivary gland biopsy in Sjogren's syndrome. AB - Labial salivary gland histopathology has long been considered to be the most disease-specific single test for diagnosis of Sjogren's syndrome. However, the diagnostic yield of widely used grading systems of focal lymphocytic sialoadenitis is rather low. Determination of the percentages IgA-, IgG-, IgM-, kappa-, and lambda-containing plasma cells in minor salivary glands obtained from a lower lip biopsy has recently been shown to be extremely valuable in Sjogren's syndrome, not only for diagnosis, but also for prognosis with regard to the development of systemic monoclonal lymphoproliferative disease. This technique greatly improves the value of labial salivary gland biopsy in Sjogren's syndrome. PMID- 1603206 TI - Ambulatory blood pressure recordings: quo vadis? PMID- 1603207 TI - Viable thoughts on viability. PMID- 1603208 TI - Experience with noninvasive ambulatory 24-hour blood pressure recording in a community hospital. AB - In 40 subjects (23 treated with antihypertensive medication), 24-h ambulatory blood pressure was measured with an oscillometric blood pressure monitor (Spacelabs model 90202). We studied applicability in the out-patient department with regard to patient tolerance, correlation with mercury manometer measurements, 24-h blood pressure variability and the use in detecting "white coat" hypertension. The measurements were tolerated quite well except for complaints of sleep disturbance and local irritation from the cuff. The average percentage of missed measuring points was 9.2%. Correlation between blood pressure with the mercury manometer and the Spacelabs monitor (averages of three consecutive readings) was: systolic 0.87 and diastolic 0.73 (P less than 0.001). No evidence for systematic error between the two methods was found. Diurnal blood pressure variation was significant with an average night-time drop of 12 +/- 15 mmHg systolic and 12 +/- 11 mmHg diastolic. "Office" blood pressure measured with the Spacelabs monitor was in the hypertensive range for 28 patients (systolic greater than or equal to 160 and/or diastolic greater than or equal to 95 mmHg). Only 15 of these subjects still met the hypertension criteria on the basis of mean daytime ambulatory blood pressure values. When ambulatory blood pressures during arbitrary 3-h periods of the daytime were studied, the number of patients with established hypertension did not change. The patients with this "office" or "white-coat" hypertensive response could not be distinguished on the basis of variability in daytime blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603209 TI - Estimation of survival probability in cirrhotics. Evaluation of a computer model applicable for decision-making. AB - In 25 randomly selected, non-alcohol-induced cirrhotics, a simple mathematical model originally designed as the "Mayo-model" for the prediction of prognosis and survival in patients with primary biliary cirrhosis, was applied using a newly developed computer program. The calculated risk scores were 4.91 for surviving patients compared to 7.65 for those who died (P less than 0.001). The survival probability at the end of the follow-up period was 88% vs 47% (P less than 0.001) for these two groups. In 12 patients of the total of 25, multiple values were calculated at yearly intervals. Usually these R values increased except in one patient with chronic active hepatitis treated effectively with corticosteroids, and for 2 others during the correction of vitamin K deficiency. Our data suggest that this model, originally designed for and validated in patients with primary biliary cirrhosis, may also be applied to predict survival in other non-alcohol induced cirrhotics and therefore may be applicable in prospective controlled trials in cirrhotics or in evaluating the need for and the timing of liver transplantation in the (near) future in these patients. PMID- 1603210 TI - A rare case of Riedel's thyroiditis, 6 years after retroperitoneal fibrosis: two diseases with one pathogenesis? AB - We describe a 70-yr-old female patient in whom both a retroperitoneal fibrosis and 6 years later a Riedel's thyroiditis were diagnosed. Both diseases belong to the group of fibrotic diseases called "multifocal fibrosis". Retroperitoneal fibrosis is now known to be an auto-allergic reaction to lipid components of the atherosclerotic process in the abdominal aorta, resulting in a fibrotic reaction around it. We hypothesize that similarly Riedel's thyroiditis is in fact a periarteritis of the carotid artery, resulting in cervical fibrosis, secondarily involving the thyroid. This hypothesis would account for the occurrence of these two rare diseases in one patient. PMID- 1603211 TI - Fatal septicaemia due to Listeria monocytogenes in a patient with systemic lupus erythematosus receiving cyclosporin and high prednisone doses. AB - Cyclosporin A is widely used in organ transplantation, preventing the rejection of multiple types of organ allografts. It is also being increasingly used as an immunosuppressive agent to treat various autoimmune diseases in patients refractory to more commonly used immunosuppressive therapy. Several trials are currently evaluating the utility of this drug associated with corticosteroids in the treatment of systemic lupus erythematosus. This case, describing a lethal septicaemia caused by Listeria monocytogenes in a patient receiving this treatment, seems to indicate that the use of these "cocktails" of immunosuppressive drugs should be particularly cautious to prevent fatal infectious complications. PMID- 1603212 TI - A case of labetalol-induced hepatitis. PMID- 1603213 TI - The importance of cytogenetic and molecular biologic abnormalities in understanding the pathogenesis of malignant diseases: an overview. PMID- 1603214 TI - Antifibrotic therapy of liver cirrhosis, with special reference to primary biliary cirrhosis: promises and limitations. PMID- 1603215 TI - Human monoclonal antibodies in sepsis. PMID- 1603216 TI - Surgical indications for intracranial arachnoid cysts. AB - Diagnostic work-up and management of intracranial arachnoid cysts are still controversial. The authors have standardized a therapeutic protocol based on the information derived from CSF contrast flow studies. The report concerns 16 cases of intracranial arachnoid cysts treated according to their protocol. PMID- 1603217 TI - Traumatic posterior fossa extradural hematomas. AB - 17 cases of operated Posterior Fossa Epidural Hematomas (PFEDH) of traumatic origin are reported. Clinical and neuroradiological findings are presented and discussed. Authors emphasize the importance of CT scan in determining a more precise diagnosis and the related improvement in the morbidity (13%) and mortality (12%) rates. PMID- 1603218 TI - Trigeminal neuralgia treated by percutaneous thermocoagulation. Comparative analysis of percutaneous thermocoagulation and other surgical procedures. AB - The authors analyze the results they obtained by percutaneous radiofrequency technique for trigeminal neuralgia. The clinical material consists of 605 cases observed from 1977 to 1986 at their Institute. There was a female preponderance (62%) and an average age of 65 years. Idiopathic, atypical and symptomatic trigeminal neuralgia has been diagnosed respectively in 568, 21 and 16 cases. From 1977 to 1980 the working temperature was above 65 C, thereafter a lower temperature has been employed to coagulate the Gasserian ganglion. The rate of pain relief was 97% for idiopathic trigeminal neuralgia, 75% for symptomatic and 21% for atypical. The loss of facial sensation accounts for 80% of side effects of this procedure in their series. The recurrence of pain was observed in 16% of cases with a follow-up ranging from 2 to 10 years. It is noteworthy that there is a correlation between the coagulation temperature and the rate of recurrence, the higher the former, the lower the latter. The authors compare their results (rate of pain relief, morbidity, mortality, rate of recurrence) with those of major reports in the literature concerning either percutaneous or other surgical procedures (mircosurgical decompression of the trigeminal nerve, glycerol injection into the trigeminal cistern and percutaneous microcompression). PMID- 1603219 TI - Cerebral vasospasm with elevated creatine phosphokinase following surgery of unruptured arteriovenous malformation. AB - Delayed cerebral vasospasm associated with marked elevation of serum creatine phosphokinase (CPK) is reported. A 21-year-old man with unruptured arteriovenous malformation (AVM) in the left temporal lobe developed postoperative symptomatic vasospasm lasting for 2 weeks. A postoperative computerized tomography scan showed intraventricular hematoma without subarachnoid hemorrhage in the basal cistern. On day 5 after surgery, the patient developed motor aphasia due to marked vasospasm around the bifurcation of internal carotid artery. On day 7 and 8, serum CPK was elevated as high as 1175 and 1376 IU/l, respectively. On day 35 when he had completely recovered from cerebral vasospasm both clinically and angiographically, the level of CPK was normalized. The causative factors of symptomatic cerebral vasospasm following surgery of unruptured AVM associated with CPK elevation are discussed. PMID- 1603220 TI - Vascular injury related to lumbar disk surgery. AB - The authors report a case of left common iliac artery injury, as a complication of diskectomy, in a 57 year-old male patient, with herniated disk at L4-L5. A review shows that L4-L5 disk space is the most common site for this rare complication of lumbar disk surgery. PMID- 1603221 TI - Intracerebral chloroma complicating acute monocytic leukemia. AB - We present the case of a 21-year-old woman with an acute monocytic leukemia. When she was in complete hematological remission, she developed rapid progressive hemiparesis on the right caused by a left frontoparietal chloroma as confirmed by surgery and histological examination. Postoperatively, the patient recovered completely, and x-ray therapy followed. Since intracerebral myeloblastic tumors are extremely rare and since the neurosurgeon may be involved in treatment of these lesions, we are encouraged to present our findings. PMID- 1603222 TI - Primary intraventricular oligodendroglioma. AB - Oligodendroglioma, usually found in the cerebral hemispheres may invade the ventricles, however primary intraventricular oligodendroglioma is quite uncommon with only a limited number of cases reported in the literature. A 39-year-old woman harbouring a primary oligodendroglioma of the left lateral ventricle was treated by subtotal removal of the tumour through a left frontal transcortical transventricular approach. The clinical, radiological and surgical details of the case are presented in correlation with the current data on oligodendrogliomas. Benefits of postoperative irradiation are stressed. PMID- 1603223 TI - Effect of naloxone on focal cerebral ischemia in cats. AB - We have examined the effects of a single injection of naloxone (5 mg/kg, i.v.) in cats with cerebral ischemia produced by transorbital occlusion of the middle cerebral artery (MCA). Cerebral blood flow (CBF) was measured and the cerebral metabolic rate of oxygen consumption (CMRO2) was estimated based on measurements of arteriovenous (A-V) oxygen difference. Six cats were treated with naloxone 30 minutes after occlusion and 8 were treated 2 hours after occlusion. In 6 control animals, naloxone produced a 10-15% increase in mean arterial blood pressure (MABP), CBF and CMRO2 lasting 30 minutes. MCA occlusion reduced CBF by 70-75% in the ipsilateral MCA territory and by 15% in the contralateral hemisphere. Naloxone increased CBF by 3.5-6% in the ischemic region and 10-22% in the contralateral hemisphere in both treatment groups to the same extent as seen in control animals. There was no significant change in A-V oxygen difference and the estimated increase in CMRO2 of non-ischemic regions of both treatment groups was similar to that of control animals. These effects were transient and lasted 15-60 minutes. We have concluded that naloxone caused a transient increase in cerebral metabolism which equals or exceeds the corresponding increase in CBF. Therefore, naloxone would not be beneficial, and may be detrimental in the treatment of cerebral ischemia. PMID- 1603224 TI - Cerebral blood flow in patients with a subarachnoid haemorrhage during treatment with tranexamic acid. AB - Many clinicians currently use antifibrinolytic therapy (AFT) routinely in the management of subarachnoid haemorrhage (SAH). Many others do not, either because they remain unconvinced that AFT reduces the risk of rebleeding, or that the medication itself causes serious complications and in particular cerebral ischaemia. Nineteen randomly selected patients were studied, 9 receiving tranexamic acid (9 g a day) and the remaining 10 placebo, with SAH confirmed by CT scanning and by lumbar puncture. There was no difference between the active and placebo group regarding the age, sex, clinical grade, CT scan and angiographic appearance. The intravenous Xe133 technique was used for serial determinations of hemispheral cerebral blood flow. The cerebral blood flow remained stable during the first week following subarachnoid haemorrhage, and then fell progressively, reaching its bottom level by the end of the second week. The cerebral blood flow levelled out during the third week at the end of which a sharp elevation, well above the first week's post-subarachnoid haemorrhage level, was noted. This rebound rise of cerebral blood flow was observed for both cerebral hemispheres. Cerebral flow was greatest in the contralateral (to side of ruptured aneurysm) brain hemisphere save for the peak observed during the first week post-subarachnoid haemorrhage. The difference between the ipsi- and contralateral hemispheres was most pronounced in patients receiving active treatment. Analysis of variance showed that cerebral blood flow was reduced by the active treatment and especially more so on the ipsilateral side with the ruptured aneurysm. The usefulness of AFT should therefore be reconsidered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603225 TI - [Follow-up of spondylodiscitis following intervertebral disk operation--on the etiology, therapy and prevention]. AB - Operations on lumbar disc prolapses are the most frequent operations in German neurosurgery divisions. After such operations, spondylodiscitis is a dreaded complication which is sometimes difficult to diagnose. Treatment of spondylodiscitis is always protracted and a burden for doctors and patients. Hence, it appears worthwhile to present a further report on discitis and spondylodiscitis, infections of the intervertebral space and the surrounding tissues after disk operations. Various clinical pictures are described: septic progress forms with neurological disorders and the necessity of open wound treatment as well as clinical pictures without septic signs with good recovery after immobilisation and antibiotic treatment. In two cases, CT-guided puncture of purulent suppuration with identification of the causative organisms and specific antibiotic treatment was possible. All patients had a relatively good result: pareses and/or bladder/rectal disorders disappeared completely in every case. The causes of discitis are discussed. The condition arises when nosocomial microorganisms, or very frequently even harmless skin bacteria, enter the wound. A large number of operations are carried out under pressure of time and under hectic conditions, as well as in a confined space in operation theatres which are too warm; these factors increase the susceptibility to infection. However, the resistance of the patient to infection is also weakened after longterm prior antiinflammatory treatment and a stay in hospital before the operation. Besides appropria to treatment of the infection (immobilisation, wound treatment, antibiotic therapy), psychological management of the patient is an important component of therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603226 TI - [Percutaneous lumbar thermal sympathectomy: method, indications and results]. AB - Thermal lumbar sympathectomy has been the method of choice since the 'eighties in the treatment of reflex dystrophy. We are using this method since January 1990. First results are presented and critically analysed. 15 patients who underwent thermal lumbar sympathectomy were examined and interviewed 1 year after treatment. 7 patients reported persisting pain relief, while the remaining 8 did not. PMID- 1603227 TI - Neurinoma of the facial nerve. AB - A case of facial neurinoma is reported. There was a progredient facial palsy persisting for one year. While X-ray examination as well as CT and MR did not show a pathological finding, classical topodiagnosis resulted in mastoidectomy, during which a neurinoma of 0.5 x 0.8 cm could be removed. The defect was reconstructed by an auricular nerve graft, with satisfactory functional results. PMID- 1603229 TI - Multiple intracranial meningiomas. PMID- 1603228 TI - Simultaneous multiple intracranial and spinal meningiomas. AB - We report on the case of a 50-year old woman with two intracranial meningiomas and two spinal ones. All were diagnosed at the same time and there were no signs of neurofibromatosis. Multiple meningiomas in different neural spaces are extremely rare, and even rarer is the simultaneous diagnosis of separate coincident lesions. The literature in this regard is reviewed. PMID- 1603230 TI - [Transient Korsakoff's syndrome after intraventricular hemorrhage]. AB - A 42 year-old man with intraventricular haemorrhage developed a transient Korsakoff's syndrome. A small arteriovenous malformation was identified on the inner side of the left parietal lobe. Cognitive disorders are very frequent after surgery on anterior communicating artery aneurysms, more rarely when the haemorrhage interest the axial anatomic loci implicating in the process of amnesic syndromes. This case illustrates well the possibility of transient Korsakoff's syndrome after pure intraventricular haemorrhage. PMID- 1603231 TI - [Spontaneous sphenoidal rhinorrhea]. AB - We describe the case of a woman, who presents a spontaneous rhinorrhea. The metrizamid computerized tomographic cisternography proves the precise anatomic location of the dural osseous defect, in the left sphenoidal sinus. Transsphenoidal approach terminated the leakage in a single procedure, without shunt. PMID- 1603232 TI - [Cisternal cysticercosis of the cerebellopontine angle. A surgically-treated case and review of the literature]. AB - Most neurocysticercosis (N.C.C.) cases reported occur in undeveloped countries where contaminated food by Taenia solium gives rise to human infection. People of developed countries are exposed by migrations and travels. We report a case of a 36 years old french woman living at La Reunion. Her symptomatology consisted of left unilateral hypoacusis progressing over a two years period accompagnied by intermittent headaches. CT scan showed a hypodense mass with a ring enhancement in the left cerebello pontine angle (C.P.A.). M.R.I. showed multicystic arrangement of vesicles in a racemous fashion that spread out to peduncular and carotid cisterns. Parenchymatous or ventricular involvement was not observed. A lateral suboccipital craniectomy was carried up in the sitting position. After division of a thickened arachnoid in the C.P.A., the vesicles were dissected an pulled out easily because the membranes had not any adhesions. Progressive improvement of hearing was observed in the next week. Primary cisternal involvement of N.C.C. is rare and, in literature, there is not any other reported case in the C.P.A. Different mechanisms of invasion to the C.N.S. are discussed. PMID- 1603233 TI - [Immunotherapy of tumors of the central nervous system]. AB - Malignant brain tumors are rapidly fatal and adjunction of chemo- and radio therapy to surgical treatment has little changed their poor prognosis. The development of basic and clinical research in immunology of brain tumors has lead to new therapeutic strategies: 1) Humoral factors: Monoclonal antibodies (MAbs): alone or conjugated (to toxins, radionucleides or chemotherapeutic agents), MAbs can theoretically recognize antigens expressed by tumor cells and reach this target with high specificity. Large amounts of tumoricidal agents could be given to the tumor with low toxic effects to normal tissues. 2) Cellular factors: LAK cells: (lymphokine-activated-killer-cells) and activated TILs (tumor-infiltrating lymphocytes) are autologous cytotoxic cells which can be produced by ex-vivo culture techniques and infused to the patient. These are very potent tumor-killer cells in vitro, however their in vivo effect is far less dramatic at the moment. 3) Cytokines: interferons, interleukins and other biological modifiers can act either directly on the tumor cells (cytotoxic effect) or indirectly through the modulation of the host-to-tumor response. 4) Combination of humoral and cellular factors: bispecific monoclonal antibodies are hybrid-molecules built from two different MAbs which can recognize two different targets, usually a tumor antigen on one hand and the T-cell-receptor (T 3) on the other hand. This combination of humoral and cellular effectors can theoretically lead to a preferential binding of effector cells to the tumor. All these new techniques are extensively studied in research laboratories and clinical trials without clear therapeutical benefit for the moment. PMID- 1603234 TI - [Medulloblastoma in children. Prognostic incidence of vascular hyperplasia, coagulation necrosis and postoperative clinical state on survival]. AB - Fifty consecutive children with cerebellar medulloblastoma were operated on May, 1971 to December, 1988. At 5 and 10-years, actuarial survival rates were respectively 46% & 42%. To determine prognostic factors, various clinical and histological features were analysed: multivariate analysis showed that increased vascularity, coagulative necrosis, and postoperative clinical status have a significant influence survival. When necrosis and/or increased vascularity were present (H+), the 5-year survival rate was 17%, whereas it was 70% when absent (H ) (p less than 0.0001). Postoperative clinical status was described as poor when neurological symptoms such as vigilance or vegetative disorders, akinesia, hypotonia, apragmatism, mutism and emaciation were associated; the 5-year survival rate was 10% in the presence of such deficits (C+) and 55% in their absence (C-) (p = 0.0002). From these results, 2 distinct groups were identified: Group 1: 23 patients without pejorative factors (H- and C-); 5 and 10-year survival rates were 80%. Group 2: 27 patients with one or two pejorative factors (H+ and/or C+); 5 and 10-year survival rates were respectively 18% and 12% (p. less than 0.0001). From our experience, it appears that histology and postoperative clinical status can be early predictors of patient outcome, since neurosurgical and radiation therapy techniques have been largely optimized. These factors could be the basis for developing adapted treatment protocols. PMID- 1603235 TI - [Cerebral metastases. A study of a surgical series of 81 cases]. AB - In this retrospective study, 81 patients operated by craniotomy for a brain metastasis are reviewed. Mean age is 56.3 years and most of the patients are male (71.6%). Clinically, 79% of the patients present a focal semiology, most frequently with neuropsychologic disturbances (43%); epilepsy is found in 31% of the cases. Symptoms related to intracranial hypertension (vomiting and headache) are present in 43% of the patients. On C.T.-scan, there is a solitary metastasis in 89% and the most common intracranial location is the frontal lobe (33.3%). The most frequent primary neoplasms are: bronchial adenocarcinoma in 19%, squamous carcinoma of the lung in 11%, melanoma in 12% and unknown origin in 18%. The surgical removal (as judged by the surgeon) is total in 70%, subtotal in 19% and partial in 11%. Standard operative mortality (30 days after craniotomy) is 7.4%. The postoperative course (till the patients leave our department) is excellent in 58% (complete neurologic recovery), steady in 20% (stability of symptoms and neurologic examination) and bad in 22%, with worsening of the neurological deficits. Most of the patients (84% of the patients who survive more than 30 days after the craniotomy) had postoperative whole brain radiotherapy with a hypofractionned schedule (total doses of 15 to 40 Gy with fractions of 200 to 650 cGy). Ten patients had surgery alone. Mean survival is 10.2 months with a follow up of 12 months to 10 years. Ten patients survived over 18 months and one is still alive almost 4 years after his craniotomy. In this study, the survival is not modified by the primary lesion's histology.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603236 TI - Malignant mesenchymoma of the brain. A case report. AB - A case of malignant mesenchymoma of the brain, containing rhabdomyosarcomatous, osteoid and cartilaginous components is presented. The patient received surgery and irradiation for his tumor, but died 10 months after the operation. Previous reports of malignant mesenchymoma of the brain are exceptional. The neurobiological behavior of this tumor is yet to be determined. PMID- 1603237 TI - European studies on the incidence of dementing diseases. EURODEM Incidence Conferences. Bordeaux, France, 1989 and Cambridge, UK, 1990. PMID- 1603238 TI - Neuropathological diagnoses in epidemiologic studies. AB - This paper discusses the potential interest of including neuropathological examination in epidemiologic studies of Alzheimer's disease (AD). Neuropathological studies could provide estimates of both false-positive and false-negative error rates of clinical diagnosis in prevalence or incidence studies on AD. To reach this objective, large and representative autopsy samples are required. Another objective could be to analyse distributions of the various modifications of the brain tissue according to age. The validity of the neuropathological examination, and particularly the level of inter- and intra observer agreement, must be further assessed before undertaking large autopsy studies in a population. PMID- 1603239 TI - Risk factors for Alzheimer's disease: the EURODEM collaborative re-analysis of case-control studies. AB - Case-control studies of risk factors for Alzheimer's disease have been hampered by low statistical power. Here, we present a collaborative analysis of 11 case control studies of Alzheimer's disease. The original data of these studies were pooled and re-analyzed. The risk factors considered in this analysis were family history of dementia and related disorders, maternal age at index birth, head trauma, medical and psychiatric history and environmental exposures. This paper gives a brief overview of the findings of the re-analysis. PMID- 1603240 TI - Epidemiologic approach to the study of dementing diseases: a nested case-control study in European incidence studies of dementia. AB - In 1994 several European studies will have available risk factor information on incident cases of dementia collected in prospective community-based studies. These centers will collaborate in a nested-case control study based on the pooled cases and a sample of the non-diseased respondents. This paper describes the general design and the risk factors to be studied in a European nested case control study of Alzheimer's disease and vascular dementia. PMID- 1603241 TI - The Paquid epidemiological program on brain ageing. AB - Paquid is an epidemiological study designed to gather and follow-up a cohort of 3,777 elderly subjects (65 years and older) living at home. In order to study normal and pathological brain ageing, these subjects were randomly chosen in the general population of 75 communities of Gironde and Dordogne, two administrative areas of South-Western France. The subjects were interviewed at home by trained psychologists and followed-up with the same procedure at 1, 3 and 5 years after the initial data collection. The identification of the demented cases is made with a two-stage design: the first stage is a systematic screening by the psychologists with application of the DSM-IIIR criteria and the second stage consists in a confirmation of the diagnosis by a neurologist according to the NINCDS-ADRDA criteria. Paquid is complemented by the study of a random sample of 357 subjects living in institutions in Gironde. PMID- 1603242 TI - Italian Longitudinal Study on Ageing: incidence study of dementia. AB - The Italian Longitudinal Study on Ageing (ILSA) is a population-based, multicentre study focusing on normal ageing and ageing pathology. Prevalence, incidence and risk factors for specific age-associated diseases, such as dementias will be investigated. A sample of 5,056 subjects 64 + resident in the field areas will be selected. The incidence rates will be estimated by using two subsequent prevalence surveys. In the first prevalence survey, each sampled subject will undergo the Mini-Mental-State examination as screening. Those who have been screened positive, will undergo an extensive diagnostic workup to identify dementia cases and to classify them as Alzheimer's disease, vascular dementia or other dementias, according to the DSM-IIIR, ICD-10R and NINCDS-ADRDA criteria. Subjects identified as non-cases will be re-assessed 3 years later by using the same procedure, instruments and criteria to estimate incident cases. Finally, genetic and environmental risk factors for Alzheimer's disease and vascular dementia will be assessed by means of case-control studies, one on prevalent and one on incident cases, and of the cohort study. The project started in January 1991. PMID- 1603243 TI - Overview of incidence studies of dementia conducted in Europe. AB - In the next 10 years findings will become available from various incidence studies on dementing diseases conducted throughout Europe. Comparisons across studies will greatly enhance our understanding of the disease process. Preliminary to these comparisons we conducted a survey of the methodology used in these studies, which is described in this report. PMID- 1603244 TI - A community-based study of dementia: the Rotterdam Elderly Study. AB - The Rotterdam Elderly Study is designed as a community-based prospective follow up study. The study population consists of almost 12,000 individuals aged 55 years and over who are living in an urban area in Rotterdam, the Netherlands. The objective of the study is to investigate the prevalence, incidence and determinants of neurogeriatric disorders, cardiovascular diseases, locomotor diseases and ophthalmologic diseases. In this paper we give a general outline of the Rotterdam Elderly Study, and a detailed description of the case finding and diagnostic procedures for the study of dementia. The risk factors for dementia that are assessed in the study are summarized. PMID- 1603245 TI - Occurrence of dementia in advanced age: the study design of the Kungsholmen Project. AB - The Kungsholmen Project is a study on elderly people living in a parish of Stockholm, Sweden. The study uses a longitudinal approach with the principal purpose of determining the natural history of Alzheimer's disease and other dementias. The study population consists of all 2,368 inhabitants of the Kungsholmen area in Stockholm, aged 75 years and above in October, 1987. The study design consists of three phases. Phase I consists of a screening test used in order to identify the 'possible' dementia cases; phase II is a complete clinical examination carried out in order to reach a final diagnosis of dementia; in phase III the whole population is reexamined in order to ascertain new cases of dementia. DSM-IIIR criteria for dementia and different types of dementia are used. The final diagnosis is based on a consensus using two preliminary diagnoses, made separately by different physicians. PMID- 1603246 TI - The MRC Multicentre Study of Cognitive Function and Ageing: a EURODEM incidence study in progress. AB - The purpose of this paper is to describe the design and methodology of this multicentre study of cognitive function and ageing, which is currently funded by the Medical Research Council (MRC) and the Department of Health for a period of 5 years. The study is designed to estimate and compare the prevalence and incidence of dementia in five centres in the United Kingdom, to examine the natural history of cognitive decline and dementia in the population and to evaluate the degree of disability associated with any decline. This will be achieved by the examination, twice, of the cognitive function of individuals aged 65 and over, with an interval of 2 years between the examinations. A 20% subsample, taken across the full range of cognitive function will be reviewed annually in more detail to chart the level of cognitive function and to ascertain a diagnosis of dementia. This represents the first systematic examination of different populations using a common methodology in the United Kingdom. PMID- 1603247 TI - Alpha: the Liverpool MRC Study of the incidence of dementia and cognitive decline. AB - The design and methods of this longitudinal study of dementia which is underway are described. An age- and sex-stratified random sample of 6,000 elderly community subjects are being re-assessed after a 2-year interval using the GMS AGECAT package. Alpha forms part of the MRC funded UK multicentre incidence study and an international network of collaborative studies using comparable measures. PMID- 1603248 TI - Epidemiology research on dementia in Antwerp, Belgium. AB - Epidemiological research on dementia in Belgium started in 1990 with a prevalence study. In the first phase of the MMSE was used for screening a random sample, stratified by age, of 1,800 aged people. In the second phase the diagnostic work was done by a psychiatrist using the CAMDEX. An incidence study will start after 2 years. Potential risk factors will be examined in a case-control study. PMID- 1603249 TI - Incidence of dementia and other psychiatric conditions in the elderly: Zaragoza Study. AB - A prevalence study of dementia and other psychiatric disturbances in the geriatric population of Zaragoza, Spain, has been completed. Our group is now planning an incidence study. The design comprises a baseline study (cross sectional study of prevalence) and a follow-up 2 years later of the cohort of non demented elderly. Both studies have two phases: the first one for screening, and the second one for the clinical diagnosis. We use the Spanish versions of the Geriatric Mental State GMS-AGECAT package, the History and Aetiology Schedule (HAS) and the Mini-Mental Status Examination (MMSE) as screening instruments. For the final diagnosis, a full protocol will be used, and the demented cases will be diagnosed according to DSM-IIIR, ICD-10 and Project Criteria. A case-control study of incident cases of dementia will be incorporated into the follow-up. Other methodological issues are analyzed. PMID- 1603250 TI - Incidence of dementia in Melton Mowbray: a proposed study and its problems. AB - This paper describes a proposed study to investigate the incidence of dementia in a population of over 75 year olds in Melton Mowbray, Leicestershire, England. The study population (n = 438) underwent a detailed psychiatric assessment using the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX) as the second stage of a survey of the physical and mental health of the elderly begun in 1988. The CAMDEX assessment and the initial screening interview included information on the majority of potential risk factors for Alzheimer's disease and vascular dementias. Together with measures of incidence and risk factors, the proposed study aims to assess the effect of the decline in mental function of the elderly, on carers, family and health services and to suggest where improvements in planning and delivery of services might be made. A number of problems arise, particularly relevant for studies of the elderly, due to the frequent follow-ups necessary for incidence studies and these are discussed. PMID- 1603251 TI - Incidence of dementia in the Lundby Study. AB - The incidences of senile dementia of Alzheimer type (SDAT) and multi-infarction dementia (MID) were studied in a total Swedish population, the Lundby project. The study is prospective and covers a 25-year period. The incidence rates per year of contracting SDAT or MID and the probability in each 10-year age interval of contracting dementia in the elderly were calculated, as well as the cumulative risk up to a certain age. The lifetime risk of contracting SDAT was for men 25.5% and for women 31.9%. The corresponding figures for MID were 29.8 and 25.1%. PMID- 1603252 TI - A longitudinal study in progress: a five-year follow-up of women aged 70-79 years living in a rural community. AB - The study in progress is a 5-year follow-up of an epidemiological investigation of the indices of dementia in women aged 70-79. From the original sample of 365 women approximately 78 had died at 5 years. Of those remaining all are being reapproached for the purpose of reassessment using the same tools as the original study and informants of both surviving and decreased participants are likewise being contacted. Observations will be made with respect to cognitive change over time. PMID- 1603254 TI - The Gospel Oak Study: the prevalence and incidence of dementia in an inner city area of London. AB - An inner city population of people over 65 years of age was screened using Short CARE in 1987. Eight percent were identified as having possible cognitive impairment and 4.7% as probable pervasive dementia, from the scores on two scales of this interview. A detailed clinical reassessment of these subjects identified by screening, suggested a rate of clinical dementia at 6.1%, 3.1% meeting the criteria for probable Alzheimer's disease. Two and a half years later, 72% have been rescreened using Short CARE. Fifteen percent of the population had died, 7% moved away and 6% were not available for interview. Thirty-five (5.9%) of the subjects rescreened appeared, from their scores on the two scales, to be new cases of dementia, giving a possible annual incidence rate of 2.6%. The annual incidence rate of probable pervasive dementia was 1.4%. These subjects are now in the process of having a detailed clinical diagnostic assessment. The medical records of those who had died between the two screens are being checked for evidence of dementia, so that more precise incidence rates can be calculated. PMID- 1603253 TI - The Cambridge Project for Later Life: design and preliminary results. AB - The Cambridge Project for Later Life is the follow-up at 2.4 years of the Hughes Hall Project for Later Life, a prevalence study of dementia in Cambridge city in which 40% of the population aged 75 and over were screened for dementia. In the follow-up, 1,173 people were screened a second time, and using Mini-Mental Scale Examination scores were selected for a more intensive interview with CAMDEX. This was followed by detailed neuropsychological testing and magnetic resonance imaging in a smaller proportion of individuals. PMID- 1603255 TI - Incidence of dementia: preliminary findings from the Nottingham Longitudinal Study of Activity and Ageing. AB - In a 4-year follow-up of 1,042 randomly sampled elderly people (aged 65+), levels of dementia were assessed using a two-phase case finding procedure (screening followed by clinical interview) among survivors. Clinical information on those not re-interviewed was provided by death certificates, hospital case notes or postal questionnaires. The unweighted 4-year cumulative incidence of dementia was 4.3%, with age-specific rates of 0.9, 2.8, 5.2, 9.0 and 8.7% for the age groups 65-69, 70-74, 75-79, 80-84, and 85-89, respectively. PMID- 1603256 TI - Geriatric Mental State-AGECAT: prevalence, incidence and long-term outcome of dementia and organic disorders in the Liverpool study of continuing health in the community. AB - The GMS-AGECAT package was used in the initial assessment and 3-year follow-up of a random sample of 1,070 elderly people living in the community. A prevalence of 4.3% is found for dementia after confirmation of diagnoses by outcome at year 3. The overall incidence of dementia was 9.2/1,000 per year after partial adjustments for outcome of year 6. Incidence per year for sub-types of dementia were AD 6.3/1,000, vascular 1.9/1,000, and alcohol-related 1.0/1,000. PMID- 1603257 TI - Methodological issues in screening for dementia. AB - Screening for dementia in populations presents particular difficulties for researchers. In the absence of gold standards for diagnosis, the methods used must be determined by the purposes of the study. In two-stage epidemiological study the screening wave and the diagnostic instrument should be considered together in relation to a third proxy gold standard such as progression of the disorder to moderate and greater severity and neuropathological diagnosis. This provides a measure of the predictive performance of the original screening method and its diagnostic phase. To reduce the variance of estimates of prevalence and incidence it is suggested that the screening interview be a subset of the diagnostic interview. PMID- 1603258 TI - Methodological problems with diagnosis of dementia in community surveys: the choice of items to study higher functions. AB - The 'global' character of dementia distinguishes it from other organic syndromes but in community surveys memory impairment is the predominant early symptom and the aphasia, apraxia and agnosia triad characteristic of dementia of Alzheimer type disease (DAT) may be hard to demonstrate. Both the Mini-Mental State (MMS) and CAMDEX contain appropriate items but information about how elderly persons in general perform on these tests is limited. This paper examines the relative difficulty of the items in a general practice sample and compares their sensitivity and specificity taking AGECAT organic diagnosis as criterion. PMID- 1603259 TI - Retardation of fetal brain cell growth during maternal starvation: circulating factors versus altered cellular response. AB - Maternal starvation inhibits fetal brain development during late gestation in the rat. To determine whether intrinsic or extrinsic factors might be the principal contributor to altered growth, brain cells from 20 day fetuses were cultured in a 96 well plate with MEM and 10% adult rat serum. Tissue growth was monitored by spectrophotometric measurement of the mitochondrial reduction of a chromagen 3 (4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT). After 1, 4 or 6 days incubation, MTT activity in non confluent cultures was shown to be directly related to tissue mass. When fetal brain cell cultures were incubated with 1% and 10% concentrations of adult rat serum, an 11-fold increase in MTT activity paralleled a 15-fold increase in tritiated thymidine incorporation. The impact of maternal starvation on fetal brain cell growth was examined by measuring MTT activity in fetal brain cells from fed and starved mothers. When cultures were incubated for 6 days with graded concentrations of fed adult serum (1.25-10%), the MTT response was slightly but consistently lower in cells from starved when compared with cells from fed mothers. By contrast, a marked difference in MTT activity which was paralleled by a lower DNA content became apparent when fetal rat brain cells were incubated with starved adult serum. Fetal serum and adult male serum were found to support growth equally well, while incubation of fetal brain cells with maternal sera resulted in lower MTT values than with the corresponding fetal sera. When cells were incubated with fetal sera pooled from starved mothers, MTT activity was decreased by 42 to 45%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603260 TI - Parameters not influenced by vesamicol: membrane potential, calcium uptake, and internal calcium concentration of synaptosomes. AB - In our previous study vesamicol, an inhibitor of the acetylcholine transporter of the cholinergic vesicles, inhibited veratridine-evoked external Ca(2+)-dependent acetylcholine release from striatal slices but did not influence acetylcholine release observed in Ca(2+)-free medium (4). Here we examined if the effect of veratridine on membrane potential, Ca(2+)-uptake, and intracellular Ca2+ concentration of synaptosomes was altered by vesamicol in parallel with the inhibition of acetylcholine release. The depolarizing effect of 10 microM veratridine (from 67 +/- 2.3 mV resting membrane potential to 50.7 +/- 2.5 mV) was not significantly influenced by vesamicol (1-20 microM). Vesamicol (1-20 microM) had no effect on either the overall curve of the veratridine-evoked 45Ca2+ uptake or the amount of Ca2+ taken up by synaptosomes. Veratridine caused a rise in intrasynaptosomal Ca2+ concentration as measured by Fura2 fluorescence, and the same increase both in characteristics and in magnitude was observed in the presence of vesamicol (20 microM). The K(+)-evoked (40 mM) increase of Ca2+ uptake and of intracellular calcium concentration were also unaltered by vesamicol. In high concentration (50 microM) vesamicol inhibited both the fall in membrane potential and the elevated Ca2+ uptake by veratridine, indicating a possible nonspecific effect on potential-dependent Na+ channels at this concentration. Vesamicol, in lower concentration (20 microM) when neither of the above parameters was changed, completely prevented veratridine-evoked increase of [14C]acetylcholine release. This was observed only when vesamicol was present in the media throughout the experiment after loading the preparation with [14C]choline.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603261 TI - Different effects of hypothermia on amino acid incorporation and on amino acid uptake in the brain in vivo. AB - The temperature dependence of the incorporation of amino acids into cerebral proteins and that of the transport of amino acids through the blood-brain barrier were studied. We measured the protein synthesis rate in vivo over a wide temperature range (14 degrees C-38 degrees C) in male Sprague-Dawley rats using a flooding dose of labeled valine. There was a linear dependence of the protein synthesis rate on temperature. The temperature quotient expressed as per cent decrease per 1 degree C was somewhat lower at the lower temperatures, a decrease from 7.8% in the 37.7-32.5 degrees C range to 6.7% in the 25.5-14 degrees C range. The transport of the three amino acids phenylalanine, lysine, and alanine, representing three transport systems, through the blood-brain barrier showed no temperature dependence in vivo. The results show that in hypothermia cerebral metabolic rates are lowered to a great extent, while some aspects of metabolic transport are not affected. PMID- 1603262 TI - Distribution of constitutive- and hyperthermia-inducible heat shock mRNA species (hsp70) in the Purkinje layer of the rabbit cerebellum. AB - In previous studies we have analyzed the effect of hyperthermia on the expression of hsp70 genes in the rabbit cerebellum using an hsp70 riboprobe which hydridized to both constitutively expressed and stress-inducible transcripts. These studies have now been extended utilizing riboprobes which are able to discriminate hyperthermia-inducible hsp70 mRNA of size 2.7 kb and constitutively expressed mRNA of size 2.5 kb. In situ hybridization with the inducible specific riboprobe revealed a prominent induction of the 2.7 kb species 1 hr after a 2-3 degrees C increase in body temperature in the following cerebellar cell types: i) Bergmann glial cells in the Purkinje layer, ii) glial cells in deep white matter fiber tracts and iii) granule neurons. The inducible transcript was not detected in the cerebellum of control animals. The constitutive specific riboprobe detected the 2.5 kb transcript in several neuronal cell types of the cerebellum such as Purkinje and granule neurons with little increase in signal in hyperthermic animals compared to controls. PMID- 1603263 TI - Effect of oxygen on ascorbic acid uptake and concentration in embryonic chick brain. AB - The effects of oxygen on ascorbic acid concentration and transport were studied in chick embryo (Gallus gallus domesticus). During normoxic incubations, plasma ascorbic acid concentration peaked on fetal day 12 and then fell, before increasing again on day 20 when pulmonary respiration began. In contrast, cerebral ascorbic acid concentration rose after day 6, was maintained at a relatively high level during days 8-18, and then fell significantly by day 20. Exposure of day 16 embryos for 48 h to 42% ambient O2 concentration decreased ascorbic acid concentration by four-fifths in plasma and by one-half in brain, compared to values in normoxic (21% O2) or hypoxic (15% O2) controls. Hyperoxic preincubation of embryos also inhibited ascorbic acid transport, as evidenced by decreased initial rates of saturable and Na(+)-dependent [14C]ascorbic acid uptake into isolated brain cells. It may be concluded that changes in ascorbic acid concentration occur in response to oxidative stress, consistent with a role for the vitamin in the detoxification of oxygen radicals in fetal tissues. However, changing O2 levels have less effect on ascorbic acid concentration in brain than in plasma, indicating regulation of the vitamin by brain cells. Furthermore, the effect of hyperoxia on cerebral vitamin C may result, in part, from inhibition of cellular ascorbic acid transport. PMID- 1603264 TI - Inhibition of transporter mediated gamma-aminobutyric acid (GABA) release by SKF 89976-A, a GABA uptake inhibitor, studied in a primary neuronal culture from chicken. AB - The effect of SKF 89976-A, a lipophilic non-substrate inhibitor of the gamma aminobutyric acid (GABA) transporter, on the release of radioactive GABA and D aspartate has been studied. Neuronal cultures from 8 day old chick embryos, grown for six days, served as a model. The cultures were incubated with [3H] D aspartate and [14C] GABA with the subsequent addition of high or low concentrations of SKF 89976-A. Finally the cultures were exposed to differently composed media for either 30 or 300 seconds. The release was quantified, using liquid scintillation counting. The efflux of [3H] D-aspartate and [14C] GABA was increased by [K+] and time, and a minimum value was obtained at [Ca2+] 1.05 mM. The release of both [3H] D-aspartate and [14C] GABA was inhibited by SKF 89976-A. The obtained results indicate that transporter mediated processes are the major mechanisms of transmitter release in the investigated model. PMID- 1603265 TI - BC200 RNA in normal human neocortex, non-Alzheimer dementia (NAD), and senile dementia of the Alzheimer type (AD). AB - BC200 RNA is a polyadenylated 200 nucleotide primate brain-specific transcript with 80% homology to the left monomer of the human Alu family of repetitive elements. Whether this transcription product contributes anything to normal brain gene function or is a residue of post transcriptional processing of brain heterogeneous nuclear RNA (hnRNA) is uncertain. However, the high abundance, tissue-specific expression and nucleotide sequence characteristics of BC200 RNA suggests that the generation of this small RNA is associated with some brain cell function. Sustained levels of the BC200 RNA transcript may be indicative of a genetically competent and normally functioning cerebral neocortex. In this investigation, we have measured the abundance of the BC200 RNA transcript in total RNA isolated from 18 temporal neocortices (Brodman area 22) of brains with no pathology and those affected with neurodegenerative disease. Neocortices were examined from 3 neurologically normal brains, 5 non-Alzheimer demented [NAD; 3 Huntington's chorea (HC), 1 amyotrophic lateral sclerosis (ALS) and 1 dementia unclassified] and 10 Alzheimer disease (AD) affected brains. Our results indicate a strong BC200 presence in both the normal brains and NAD affected neocortices, but a 70 per cent reduction in BC200 signal strength in AD afflicted brains. These results may be related to the observation that Alzheimer brains exhibit marked deficits in the abundance of neuron-specific DNA transcripts; these deficits are consistent with the idea that AD is characterized by an impairment in the primary generation of brain gene transcription products. PMID- 1603267 TI - Abstracts of communications of the Japanese Society for Neurochemistry. 34th annual meeting. Tokyo, October 14-16, 1991. PMID- 1603266 TI - Lipid peroxidation and antioxidant enzymatic systems in rat retina as a function of age. AB - In the present study, we have assayed the enzymatic activity of Cu,Zn-SOD, Mn SOD, GSH-Px, GSH-Red, Cat, and G6PD in rat retina as a function of age. Conjugated diene levels and MDA formation were also determined. The conjugated diene levels in rat retina were found to increase significantly with age, accompanied by a marked decrease in GSH-Px and Cat activities. No age-related change in MDA levels and in GSH-Red and G6PD activity was found, whereas a significant increase in SOD activity was observed between 1 and 4 months. Decreased GSH-Px and Cat activity is related to increased lipid peroxidation with age. PMID- 1603268 TI - [Histological diagnosis of brain tumors: (22). Arachnoid cyst and Rathke's cleft cyst]. PMID- 1603269 TI - [Operative techniques for lipomyelomeningocele]. PMID- 1603270 TI - [Intraoperative use of real-time ultrasonography in neurosurgery: with special reference to head injury and intracerebral hemorrhage]. AB - We used B mode ultrasonography during 61 craniotomies performed in the acute stage after head injury, intracerebral hemorrhage, ruptured cerebral aneurysm and so on. We examined intracerebral lesions, new hemorrhages near the operative field, and contralateral hemorrhages appearing simultaneously intraoperatively. The resolution with ultrasonography was similar to that of CT and had few obstructing artifacts. It was easy to use and very useful for diagnosing abnormal intracranial mass lesions during craniotomy, mainly for the acute stage of head injury or intracerebral hemorrhage. PMID- 1603271 TI - [Management of elderly patients with aneurysmal subarachnoid hemorrhage]. AB - Clinical features of 61 elderly patients aged over 70 years with ruptured intracranial aneurysms were compared with those of 328 younger patients aged under 70 years. According to a policy of early operation, elderly patients with Hunt and Kosnik's grade I, II and younger patients with grade I, II, III were operated on in the acute stage. In elderly patients with grade III, IV and younger patients with grade IV, the indication for surgery was determined case by case. Surgery was performed on 29 patients (48%) in the elderly group and 277 patients (86%) in the younger group. Our conclusions are as follows: 1. Regarding cases of grade I, II and III of Hunt and Kosnik's classification, the rate of good outcome in the elderly group was similar to that in the younger group, following early surgery and meticulous post-operative care. 2. In the elderly group, no patient in cases of grade IV obtained good surgical outcome. 3. Symptomatic vasospasm was less frequent in elderly patients (18.8%) than in younger cases (37%). 4. Delayed operation was planned for some patients in the elderly group, but none of them underwent surgery because of rerupture of aneurysms and deterioration of general condition. PMID- 1603272 TI - [Evaluation of the surgical results of the interhemispheric approach in comparison with the pterional approach for anterior communicating artery aneurysms]. AB - From 1986 to 1990, 77 cases of ruptured anterior communicating artery (Aco) aneurysms have been operated on through an interhemispheric approach or a pterional approach. In this study, we mainly investigated the following factors: surgical outcome, surgical complications, degree of evacuation of subarachnoid clot, and frequency of symptomatic vasospasm. The difference of outcome between the two surgical groups was not statistically significant. Each operating method had characteristic surgical complications. Pterional approach had a tendency to complicate premature rupture, sacrifice small vessels around the aneurysm, and to result in Korsakoff syndrome and inadequate clipping. Interhemispheric approach was apt to complicate cerebral contusion, bilateral olfactory nerve injury and hemorrhagic infarction due to sacrifice of the bridging veins. The pterional approach could evacuate more of the subarachnoid clot than could the interhemispheric approach, but there was no significant difference in frequency of symptomatic vasospasm depending on which method was used. PMID- 1603273 TI - [Treatment of metastatic brain tumors: effect of surgery of multiple metastatic brain tumors and systemic metastasis with special reference to quality of life]. AB - To assess the efficacy of surgical resection of brain metastases from patients with multiple brain metastases or/and with other systemic metastases, the authors analysed treatment results of 90 cases of metastatic brain tumors. The patients were divided into three groups. Group A (nine cases): Patients with single brain tumor and their primary cancers were well controlled. Their brain tumors were removed surgically and followed by radiation. Their mean survival time was 17.0 months, and 14.6 months were independent (Karnofsky score greater than or equal to 70) in cases of lung cancer. Five patients (55.6%) improved by treatment. Group B (21 cases): Patients with multiple brain metastases or/and with systemic metastases. Their brain tumor(s) which gave rise to neurological symptoms were surgically removed in order to improve their quality of life. In cases of lung cancer, mean survival time was 9.5 months and 7.1 months were independent. 11 patients (52.3%) improved by treatment. Group C (60 cases): Patients treated conservatively. Their mean survival time was 4.9 months and 2.7 months were independent in cases of lung cancer. Only 13 patients (21.7%) improved by treatment. However 23 (38.3%) deteriorated in their quality of life during treatment. Two patients of this group had single brain tumor and their primary cancers were controlled well. They refused surgery. Their mean survival time was 13.0 months, and 7.0 months were independent. These times were statistically shorter than group A. Seven patients had similar systemic and neurological states as those in group B. Their mean survival time was 5.0 months and 3.0 months were independent. These times were also statistically shorter than those in group B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603274 TI - [Ventriculoperitoneal shunt using a continuously variable-resistance valve for management of hydrocephalus, especially for cases mimicking simple brain atrophy]. AB - Twenty-two hydrocephalic patients with a ventriculoperitoneal shunt using a continuously variable flow resistance valve (Orbis-Sigma valve system; Cordis Corporation, USA) were reviewed to discuss usefulness of the shunt system. We divided the cases into two groups according to the demonstration of the cortical sulci in computed tomography (CT) as follows; A: progressive hydrocephalic cases mimicking simple brain atrophy, B: acute or subacute hydrocephalic cases with evidence of increased intracranial pressure. Patients in Group A had begun to present slowly progressive loss of activity, dementia and gait disturbance of various degrees after a long quiescent period following primary central nervous system injury. CT findings of these cases showed they were mimicking simple brain atrophy. Although the period of their deterioration was very long, ranging from 1 month to nine years, clinical signs improved in all cases after the shunt. None showed complications. Group B cases consisted of those with signs of increased intracranial pressure such as consciousness disturbance, nausea and vomiting. These cases showed poor demonstration of the cortical sulci in CT. Eleven out of thirteen cases showed satisfactory clinical improvement, though the size of the ventricle showed a slight decrease following shunt procedure. Only one case showed unilateral subdural effusion. In conclusion, this shunt system is useful for the management of ventricular enlarged cases mimicking simple brain atrophy as well as acute hydrocephalic cases. Troublesome consequences such as subdural effusion and hemorrhage rarely occur even in cases with low cerebrospinal pressure. PMID- 1603275 TI - [One-year follow-up study of patients with severe head injury; comparison of outcomes for focal and diffuse brain injuries]. AB - Forty patients with severe head injury were classified on the basis of initial CT findings into 2 groups of focal injury (n = 20, mean age = 55.2 years), and diffuse injury (n = 20, mean age = 45.0 years). Glasgow Outcome Scale (GOS) status at 2 post-injury intervals (at discharge and 1 year after injury) of the 2 groups were compared and prognostic factors examined. At discharge (less than 3 months after injury), there were slight differences between the 2 groups in GOS score distribution, with nearly half of the patients in each group being independent. One year after injury, mean GOS score of the focal injury group was relatively more favorable, with about 60% of patients being independent, while no significant improvement was observed in the diffuse injury group. With the exception of brainstem signs, in both groups, the parameters of type of lesion detected on initial CT, modality of treatment, patient age, and operative timing all proved of little prognostic value. Brainstem injury due to intracranial mass lesions or postoperative brain edema was presumably a critical factor affecting prognosis in the focal injury group, while both primary and secondary brainstem injuries could have been major factors affecting prognosis in the diffuse injury group. In the prognosis of patients with severe head injuries, not only the parameter of initial CT findings but also time course of changes in brainstem signs, serial CT findings, MRI, and electrophysiological analyses such as motor evoked response should be considered. PMID- 1603276 TI - [Peripheral aneurysms of the posterior inferior cerebellar artery; analysis of 15 cases]. AB - Peripheral aneurysms of the posterior inferior cerebellar artery (PICA) are rare. The authors report 15 cases of peripheral PICA aneurysms. Twelve of the aneurysms were discovered after their rupture and two were discovered after rupture of concomitant AVM, and one was detected incidentally. As to the location of aneurysms, more than half of the aneurysms arose at the telovelotonsillar segment. One patient had 2 aneurysms on the same peripheral PICA, which were not obvious on preoperative angiography because the ruptured one was partially thrombosed. Another rare case with aneurysm located at the internal auditory meatus is also reported. The findings of CT were characteristic, namely hemorrhage in the fourth ventricle without obvious hemorrhage in the basal cisterns, or only within the cerebellar vermian cistern. This phenomenon strongly suggested the possibility of rupture of peripheral PICA aneurysms. As to the surgical results, 10 patients (71%) of the 14 patients had a good recovery, and 1 patient (7%) with nonrupture aneurysm had a fair result due to pre-existing pontine hemorrhage. Three patients (21%) died. Rebleeding occurred in 3 patients, but cerebral vasospasm occurred in only 1 patient. Consequently, as peripheral PICA aneurysms are likely to be missed, and rebleeding is an unfavorable factor, one should try to demonstrate aneurysms with angiography, by using various methods such as subtraction or magnification. PMID- 1603277 TI - [Intraparenchymal granulocytic sarcoma in acute monocytic leukemia; case report]. AB - Granulocytic sarcoma of the parenchyma of the brain present in a patient with acute monocytic leukemia, and its unusual course during treatment, is described. Four years after diagnosis of acute monocytic leukemia, a 24-year-old man developed severe headache during its remission period. The CT scan showed large intraparencymal mass in the right frontal lobe, which was partially removed and diagnosed as granulocytic sarcoma. Following the operation, radiation in total dose of 35.5 Gy was given to the whole brain, and there was also left intraventricular administration of methotrexate (MTX) and cytosine arabinoside (ara-C). The treatment resulted in the complete disappearance of the intraparenchymal mass apart from small calcifications. Five months later, the patient redeveloped severe headache with consciousness disturbance. CT scan revealed marked swelling in the left cerebral hemisphere with irregular contrast enhanced areas. The patient died of brain herniation in spite of conservative therapy. Photomicroscopic findings of the left cerebral hemisphere proved the presence of "disseminated leukoencephalopathy" and the absence of tumor cells. On the other hand, the right frontal lesion consisted of no tumor cells but scar tissues. This unusual feature of the CT scan in the terminal stage might be caused by combination with the effect of highly concentrated MTX in the left cerebral hemisphere because of the increased permeability of the ependym and the relatively high radiosensitivity in the non-affected left cerebral hemisphere. PMID- 1603278 TI - [A rare case of delayed traumatic Millard-Gubler syndrome]. AB - We reported a rare case of traumatic Millard-Gubler syndrome exhibiting right peripheral facial palsy and right abducens palsy plus left hemiparesis. A 60-year old male patient was admitted to our department due to tetraparesis. He fell down and struck his neck and shoulder. Several hours later he was aware of muscle weakness in all extremities. On admission neurological examination revealed right peripheral facial palsy, right abducens palsy and left hemiparesis suggesting Millard-Gubler syndrome. CT demonstrated a high density mass in the prepontine cistern. MRI showed an iso intensity mass compressing the right ventral surface of the pons at T1 weighted and low intensity at T2 weighted image. The presence of a subarachnoid hematoma in acute stage was suggested. This is the third case report of traumatic Millard-Gubler syndrome in literature. Its etiology and the mechanism are discussed here. We tend to conclude that, in addition to direct damage, its mechanism can be attributed to vasostenosis of the perforators from the basilar artery compressed by the prepontine subarachnoid hematoma. PMID- 1603279 TI - [Interhemispheric arachnoid cyst; report of three cases]. AB - Three operated cases of the interhemispheric arachnoid cyst were reported. Case 1: a 58-year-old female suffering from progressive right hemi-rigidity and gait disturbance for the past two years. Case 2: a 66-year-old female was admitted with chronic headache. MRI demonstrated a large interhemispheric cyst in these two patients. Case 3: a 6-month-old male had frequent episodes of tonic seizure. MRI demonstrated interhemispheric cyst and agenesis of the anterior part of corpus callosum. The resection of the cystic wall via the interhemispheric approach was performed for all cases. General convulsive seizure developed in the early stage following operation in case 1 and case 2, in spite of routine administration of prophylactic anticonvulsant. The seizures were well controlled thereafter. In all cases, the cyst disappeared on the follow up CT. Simple resection of cyst wall is effective in the surgical treatment of interhemispheric arachnoid cysts. PMID- 1603280 TI - [Disproportionately large, communicating fourth ventricle; report of 4 cases]. AB - Although both "Isolated Fourth Ventricle" (IFV) and "Disproportionately Large, Communicating Fourth Ventricle" (DLCFV) are the clinical-radiologic entities characterized by a dilatation of the fourth ventricle, DLCFV must be separated from IFV because of its apparent patency of the aqueduct. In some Japanese literature, however, there was some confusion concerning DLCFV and so-called "reversible DLCFV" or IFV with "one way aqueduct". In this paper, comparing DLCFV with IFV, a reasonable pathogenesis of DLCFV was discussed on the basis of clinico-radiological analysis of four cases of DLCFV. Our tentative conclusion is as follows: 1) Whether there is radiologic aqueductal patency or not, the term of DLCFV should not be primarily reserved for patients who have had shunting of the lateral ventricle for previous hydrocephalus." 2) It was strongly suggested that a mechanism involved in the development of DLCFV was the formation "membranous occlusion" in/or near the foramen Magendie. PMID- 1603281 TI - [A case of dural sarcoidosis]. AB - A 26 year-old man, who was treated for meningitis in our hospital previously, was rehospitalized 1 year later because he developed disturbance of consciousness, gait disturbance and urinary incontinence. Blood examination revealed accelerated ESR, elevated GPT, slight elevation of serum Ca, strong positive CRP, and a decrease in PHA and Con A. ACE was within normal range and tuberculin reaction was negative. Lumbar puncture revealed that the initial pressure was 310 mmH2O, cells were 152/3, and protein was 343 mg/dl. Bilateral hilar lymphadenopathy was absent in chest X ray film. Head CT revealed enlarged lateral ventricles and irregularly enhancing nodular lesions in the anterior half of the falx cerebri, and abnormally strong enhancement of the choroid plexus. Ventriculoperitoneal shunt was performed. As a diagnosis was difficult to obtain from the clinical data, biopsy of the nodular lesions was performed. The histopathologic diagnosis was sarcoidosis. Steroid hormone was administered thereafter, and the nodular lesions of the falx disappeared in the follow-up. In the literature, only 8 cases of sarcoidosis of the dura mater have been reported. Since intracranial sarcoidosis is a part of systemic sarcoidosis, its diagnosis is not difficult in most cases. However, in cases difficult to diagnose as in our case, biopsy may be necessary. When nodular lesion occurs in the dura mater, sarcoidosis must be included as a possibility in the differential diagnosis in addition to the usual meningioma, lymphoma, and metastatic brain tumor. PMID- 1603282 TI - [A case of bilateral panophthalmoplegia caused by paranasal malignant lymphoma extending into the skull base]. AB - A case of bilateral panophthalmoplegia developed after paranasal malignant lymphoma is described, and previously reported cases are reviewed. A 74-year-old female was hospitalized with the chief complaints of bilateral ptosis and bilateral deep orbital pain that had developed over a 10-day period. Neurological examination revealed bilateral dilated pupils, panophthalmoplegia, and hypalgesia in the area of the ophthalmic nerve on both sides. Laboratory studies and endocrinological examination were free from abnormal findings. Skull X-ray films showed a soft tissue lesion in the sphenoidal and ethmoidal sinus and this was associated with bony structure destruction in the surrounding area. Computed tomography demonstrated a heterogeneously enhanced mass lesion in the paranasal sinus extending into the intrasellar region and bilateral cavernous sinus. Meticulous investigation has so far revealed no distant lesions either in the thoracic or abdominal lesions. Subtotal tumor resection was undergone via the transsphenoidal route at which time tumor extension into the nasal cavity and sellar floor destruction were confirmed. Diffuse and mixed B-cell type malignant lymphoma was the pathological diagnosis. Postoperatively, improvement of abnormalities of pupils, panophthalmoplegia, and ptosis was achieved but this was only transient. Despite focal radiation therapy and repeated chemotherapy, the patient died 14-months after the diagnosis was made. On reviewing the literature, it is shown that the incidence of bilateral panophthalmoplegia among patients who develop disturbance of ocular movement is extremely low (0.4%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603283 TI - Development and perinatal risk factors of very low-birth-weight infants. Small versus appropriate for gestational age. AB - 371 long-term surviving very low-birth-weight (VLBW) infants born between July 1983 and June 1986 with a birthweight under 1501 g were followed-up. This sample amounted to 91% of such infants of six neonatal intensive care units in Hamburg (Germany). A neurological examination and a developmental evaluation using the Griffith Developmental Scale were carried out at the age of 18 to 20 months, corrected for gestational age. Ninety-six of the 371 infants were small for gestational age (SGA), 275 appropriate for gestational age (AGA). Striking differences between these two groups were found concerning perinatal risk factors and neurological outcome. Maternal risk factors associated with intrauterine growth retardation such as maternal toxemia and signs of fetal stress were found in a high percentage of the mothers of SGA-children, factors associated with premature labor and chorioamnionitis in mothers of AGA-children. Cerebral palsy was detected in only 7% of the SGA-children but 17.5% of the AGA-children. The difference in the development of cerebral palsy was attributed mainly to different postconceptual ages of the SGA- and AGA-children. In general, minor neurological abnormalities were detected in as many as 30% of SGA- and only 15.3% of AGA-children. None of the SGA-children over 33 weeks of gestational age developed cerebral palsy, but 25% minor neurological abnormalities. As to cerebral palsy the prognosis of SGA-infants with a very low birthweight is not different from AGA-infants with a similar gestational age. Regarding the development of minor neurological abnormalities, however, intrauterine growth retardation seems to be a risk factor independent from gestational age. PMID- 1603285 TI - N-acetylaspartic aciduria in young age. PMID- 1603284 TI - Extramedullary hematopoiesis of the cranial dura and anhidrotic ectodermal dysplasia. AB - A 2-year-old amerasian male with anhidrotic ectodermal dysplasia (Christ-Siemens Touraine Syndrome) was admitted for status epilepticus and Mycobacteria avium intracellulare infection. A computed tomography scan of the head revealed a mass thought to be a subdural hematoma. The patient died following overwhelming Mycobacteria avium-intracellular and Pseudomonas aeruginosa sepsis. Autopsy revealed extensive extramedullary hematopoiesis of the dura forming a tumor-like thickening with focal subdural hemorrhage. To our knowledge, this is the first report of extramedullary hematopoiesis of the cranial dura associated with anhidrotic ectodermal dysplasia. PMID- 1603286 TI - A comparison of neurological assessment scores from two cohorts of low birthweight children evaluated at age four years: Dublin and Copenhagen. AB - We compared the neurological condition and functions at age 4 years for two cohorts of children initially treated in the neonatal intensive care units in two countries: Denmark (10) and Ireland (2). The comparisons were made in two ways: first, the more usual comparison between frequencies of cerebral palsy, mental retardation, hydrocephalus, visual and hearing loss. A second comparison was based on the items, subscales, and total scores on a neurological battery developed from the Danish data. Comparisons were made among three different birthweight groups within each country as well as between countries using analysis of variance (ANOVA). In both cohorts, significant differences were shown between two subgroups: those with birthweights less than 2300 gms and those with birthweights over 2500 gms for all subscales except the neurological ones in the Irish cohort. In the Danish cohort, significant differences were shown on all subscales among three birthweight groups: less than 1501 gms; 1501-2300 gms; and over 2500 gms. Significant differences were shown between countries for easy drawing, neurology "b", and fine motor testing. PMID- 1603287 TI - Assessment of brain maturation by T2-weighted MRI. AB - MRI is a noninvasive method to assess the maturation of the brain. T2 values decrease after birth in proportion to histologically ascertained maturational changes of cortical and subcortical structures. T2 values of 8 anatomical brain structures were sampled in 5 healthy children aged 8 years, four healthy children aged 10 years and 8 healthy adults aged 24 or 25 years. The results of the study indicated that T2 values decrease after the first decade of life, consistent with maturational changes of the CNS persisting into the 2nd and 3rd decades of life. PMID- 1603288 TI - Polygraphy after discharge in preterm infants with and without apnea in the nursery. AB - Nine of nineteen infants in this study exhibited two or more central apnea greater than or equal to 20 seconds when they were older than one week and between 32-36 weeks postconceptional age (PCA). We focused on the sequelae of these apneas. Apnea was separated from other morbidity associated with immaturity by the selection of consistently healthy infants. Following discharge, polygraphic tracings were obtained at 40, 44 and 52 weeks PCA in these non-apneic and previously apneic infants. Sleep states, minute by minute values for heart and respiratory rate, skin temperature and transcutaneous O2 (PtcO2) and CO2 (PtcCO2), apnea and transient decreases in PtcO2 were determined. Polygraphic measurements did not differentiate preterm infants with late apnea in the nursery from non-apneic ones. However, the apneic group exhibited a transient decrease in awakenings at 44 weeks PCA. PMID- 1603289 TI - Maturation of set-modulation of lower extremity EMG responses to postural perturbations. AB - To analyse the influence of different "postural sets" on stance stabilizing EMG responses in children, EMG responses to toe-up tilt perturbations were recorded in 70 children between the age of 9 months and 10 years, as well as in a control group of 10 adults under different postural set conditions, using either bilateral destabilization with eyes opened, eyes closed, or introducing additional minute upper extremity support. Recordings were also made with the children seated in front of the platform with the ankle joint angle being identical to that in the standing condition. Also recordings were made after unilateral destabilization in bilateral lower leg muscles, to determine if there is a generalization of EMG response patterns to the mechanically not disturbed side. Across all age-groups the principal modulation of EMG response changes according to postural conditions was identical. Long latency (LL) EMG responses were down-regulated when additional upper extremity support was provided. LL responses were abolished in the sitting condition. With unilateral destabilizations throughout all age-groups short latency responses were restricted to the perturbed side, whereas long latency responses could be obtained symmetrically. The proximal to distal gradient of recruitment of muscle groups, remained identical across all age-groups. The data indicate that the basic organizational principle of stance stabilizing EMG responses and their modification by postural sets remains invariant across development. This indicates that the involved organizational principles are present as soon as a child is able to stand upright and are not subject to further shaping by motor learning. PMID- 1603290 TI - Relationships between psychomotor retardation and EEG power spectrum in major depression. AB - In 63 depressed patients, the associations between severity of depression, psychomotor retardation, assessed by the Bech-Rafaelsen Melancholia Scale, and EEG spectral analysis were examined. Slow EEG activity (theta 2/alpha 1 bands) was positively and fast activity (alpha 3/beta bands) negatively correlated with the observed retardation. Out of the four retardation subitems (motor, verbal, intellectual and emotional), motor retardation was closest correlated with slow EEG activity. PMID- 1603291 TI - Clinical studies with oxiracetam in patients with dementia of Alzheimer type and multi-infarct dementia of mild to moderate degree. AB - The cognitive and behavioral effects and the safety of oxiracetam therapy during a placebo-controlled trial and the relevant follow-up up to 1 year in patients with senile dementia of Alzheimer type (SDAT) and multi-infarct dementia (MID) of mild to moderate degree were studied. Sixty male and female outpatients participated in the double-blind, placebo-controlled, parallel-group, randomized trial, comparing the effects of oxiracetam 800 mg b.i.d. and placebo during 90 days of treatment. At the end of therapy, statistical analysis evidenced significant improvements in the group receiving oxiracetam in respect to the placebo group on Mini Mental State Examination, Auditory Continuous Performance Test, Rey's 15 Words Test, Block Tapping Test, Mattis Word Fluency, Luria Alternating Series and Instrumental Activities of Daily Living. Afterwards, 29 of the 30 patients who received oxiracetam, participated in the open follow-up study, receiving 800 mg b.i.d. oxiracetam for a total standard period of 1 year. Statistical improvements in comparison to baseline were again found on the same tests of the first 90 days (except for Rey's 15 Words Test) and on the Memory item of the Inventory of Psychic and Somatic Complaints Elderly. During the late phase of the follow-up, statistically significant worsenings in comparison to baseline were observed on Digit Span Backward, Gibson's Spiral and some non memory items of IPSC-E. Neither severe adverse events were observed during the whole study, nor changes in routine laboratory examinations. In conclusion, in the present population of patients with mild to moderate degree dementia, the safety of 1,600 mg/day of oxiracetam also up to 1 year of treatment was confirmed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603292 TI - Cigarette smoking and nicotine gum (0, 2 and 4 mg): effects upon four visual attention tasks. AB - Sixteen regular smokers, abstinent for 12 h prior to testing, were assessed on a battery of four visual attention tasks: rapid visual information processing (RVIP), letter cancellation, Stroop, and width of attention. Each subject was assessed under four conditions: placebo gum, 2 mg nicotine gum, 4 mg nicotine gum, and cigarette smoking (own brand), with the order of drug administration determined by latin square. Pre-post drug difference scores for letter cancellation response time demonstrated a significant monotonic dose-response function, with significantly faster performance following cigarette than placebo. RVIP response time and target detection were also affected by nicotine. One RVIP task parameter demonstrated a significant monotonic dose-response function, with highest performance under smoking. Other RVIP measures demonstrated curvilinear dose-response functions, with highest performance under nicotine gum, and broadly similar performance after placebo gum and cigarette smoking. Monotonic and inverted-U arousal/performance functions similar to these have been demonstrated in previous research with nicotine. In contrast to the significant changes in sustained attention, neither width of attention nor Stroop task performance (an index of distractability) was affected by nicotine. Resting heart rate and subjective 'need for a cigarette' showed the predicted monotonic dose-response functions following nicotine. There were no significant changes in any Profile of Mood State factor. PMID- 1603293 TI - Behavioral restraint and symptoms of attention deficit disorder in alcoholics and pathological gamblers. AB - Adult alcoholics as well as pathological gamblers reported that, as children, they had higher than control levels of attention deficit disorder-related behaviors. On the other hand, alcoholics and only a subset of gamblers showed deficits in a test of behavioral restraint. PMID- 1603294 TI - Imipramine-induced jitteriness and decreased serum iron levels. AB - Jitteriness appears to be a specific side effect of tricyclic antidepressant treatment in panic disorder patients. In addition, the patients with jitteriness have lower serum iron levels compared to those that do not develop jitteriness (p = 0.01). PMID- 1603295 TI - Semantic memory impairment in Alzheimer's disease: failure of access or degraded knowledge? AB - A battery of neuropsychological tests designed to assess semantic knowledge about the same items both within and across different modalities was administered to a group of 22 patients with dementia of the Alzheimer type (DAT) and 26 matched controls. The DAT patients were impaired on tests of category fluency, picture naming, spoken word-picture matching, picture sorting and generation of verbal definitions. A relative preservation of superordinate knowledge on the sorting and definition tests, as well as a disproportionate reduction in the generation of exemplars from lower order categories was noted. Analysis of the errors made by each patient across the different tests, revealed a significant correspondence between the individual items. These findings offer compelling evidence that the semantic breakdown in DAT is caused by storage degradation. PMID- 1603296 TI - Contribution of the cerebellum to neuropsychological functioning: evidence from a case of cerebellar degenerative disorder. AB - A detailed neuropsychological evaluation was performed on a patient with an idiopathic cerebellar degenerative disorder. Significant deficits were found in verbal and nonverbal intelligence, verbal associative learning, and visuospatial skills. These deficits were not readily explained by motor control difficulties. In contrast to the patient's moderately impaired language abilities, he was severely impaired on a test of verbal fluency and demonstrated mild naming deficits. Severe cerebellar parenchymal volume loss was demonstrated by magnetic resonance examination. Supratentorial structures showed only minimal posterior parietal and occipital sulcal prominence. On neurological examination, this patient had signs of severe involvement of the cerebellar systems and mild-to moderate dysfunction of the corticospinal tract. As is characteristic of patients with cerebellar degeneration, there was neurophysiological evidence of subclinical involvement of auditory and somatosensory pathways at the level of the brain stem. Since relatively little cerebral cortical atrophy was noted in this patient, these findings suggest that an intact cerebellum is important for normal cognitive functions. PMID- 1603297 TI - Lateralized deficits in visual attention in males with developmental dopamine depletion. AB - Children with early treated phenylketonuria (ETPKU), a disorder associated with developmental dopamine depletion, were tested with a visual orienting paradigm to determine the existence of lateralized deficits in specific attentional operations. Male ETPKU subjects showed a right visual field impairment in disengaging attention, indicating left hemisphere dysfunction, and overall slowed reaction times. Female ETPKU and normal subjects did not differ. The results suggest that for males, dopamine depletion disrupts left hemisphere function. This finding has important implications for disorders with suspected developmental dopamine abnormalities, and may also illustrate how sex differences in functional lateralization develop in the normal brain. PMID- 1603298 TI - Sex differences in interhemispheric reorganization of speech. AB - Ninety-four epileptic patients who had undergone the carotid amytal test were evaluated in order to determine whether sex affects the pattern of hemispheric reorganization following cerebral injury. Our data suggest that the period during which hemispheric reorganization for speech can occur differs between the sexes. Females have a relatively short window, with reorganization most likely during the first year of life. The length of this window is more difficult to define for males but may extend until puberty. The period during which a shift to left handedness can occur does not appear to be affected by gender. Here, both males and females seem to show a relatively short window. PMID- 1603299 TI - The effects of Kanji attributes on visual field differences: examination with lexical decision, naming and semantic classification tasks. AB - Using three experimental tasks (lexical decision, naming and semantic classification), the relative contribution of various Kanji attributes in left and right visual field recognition was examined. The results showed that first, factors contributing to the left visual field processing of Kanji differed depending on the level of processing; second, in an early stage of processing, perceptual attributes such as the number of strokes was a strong contributing factor; and third, in a later stage both perceptual- and imagery-related attributes contributed strongly to left visual field or right hemisphere processing. PMID- 1603300 TI - Cluster analysis reveals at least three, and possibly five distinct handedness groups. AB - Multivariate techniques have used data from hand preference questionnaires to group hand preference items, but no attempt has been made to date to use multivariate analyses to group individuals in terms of handedness groups. This study analyzed the responses of 645 subjects on the Waterloo 60-item handedness questionnaire with a cluster analysis (BMDP) in order to determine the grouping of individuals in terms of hand preference patterns. Five distinct handedness groups were recognized by this procedure and a Discriminant Function Analysis revealed a very high accuracy of assigning individuals to the five groups. A cluster analysis of a shorter 14-item questionnaire suggested three distinct handedness groups, and the degree of accuracy of assigning individuals to these groups was also very high. As is the case with all multivariate techniques in neuropsychology, the question of whether the clusters form meaningful groupings awaits an answer in terms of their different neuropsychological properties. PMID- 1603301 TI - Another look at categorical priming in the cerebral hemispheres. AB - This study investigated the effect of exemplar dominance on semantic priming in the left and right visual fields for words that are members of the same category, but not strongly associated. A low proportion of related primes was employed in lexical decision and word pronunciation tasks to assess the automatic activation of word meanings in each cerebral hemisphere. Priming was reliably obtained only in the LVF/right hemisphere. In addition, this effect did not vary with category dominance of the prime:equivalent LVF priming was observed for ROBIN-CROW (high dominant) and DUCK-CROW (low dominant) pairs. These findings support the view that a broader range of related meanings is activated during word recognition in the right, than in the left, hemisphere. PMID- 1603302 TI - Perception of moving and stationary gratings in brain damaged patients with unilateral spatial neglect. AB - Contrast sensitivity for stationary and drifting sinusoidal gratings of different spatial frequencies was measured in 17 brain damaged patients (five left-brain damaged and 12 right-brain damaged patients, six of whom showed symptoms of spatial hemi-neglect). Twenty-nine combinations of spatio-temporal stimuli were considered in the drifting condition. No specific deficit for the group of patients with neglect symptom in the perception of moving and stationary gratings was observed. Also, no systematic deficit for perceiving the direction of motion- toward the neglect hemispace or away from it--was apparent. A small, selective impairment in the detection of stationary or very slow drifting gratings of low spatial frequency was observed in the presence of unilateral cortical damage, independently from its side (left or right) and from the presence of neglect. Some difficulty to detect the direction of motion was observed in a few individual patients. PMID- 1603303 TI - Atypical presentation of Lhermitte-Duclos disease: preoperative diagnosis with MRI. PMID- 1603304 TI - MRI of syphilitic myelitis. AB - MR imaging was performed on a patient with syphilitic myelitis. T2-weighted images showed high intensity areas in the thoracic spinal cord. On T1-weighted images after gadolinium-DTPA injection, heterogeneous enhancement was observed in the superficial portion of the spinal cord. The intramedullary high intensity areas on T2-weighted images disappeared after antibiotic therapy. PMID- 1603305 TI - Neurofibromatosis with dural ectasia and bilateral symmetrical pedicular clefts: report of two cases. AB - We present two cases of bilateral, symmetrical pedicular clefts associated with dural ectasia in von Recklinghausen's disease (neurofibromatosis). In one case the pedicular cleft was at the T12 level, while in the other it was at L4, and was responsible for spondylolisthesis. Two hypotheses are advanced to explain the cleft: (1) a congenital, dysplastic osseous defect and (2) bilateral stress fractures related to thinning of the pedicle caused by dural ectasia. PMID- 1603306 TI - Multiple occult vascular malformations of the brain and spinal cord: MRI diagnosis. AB - We report a patient with multiple angiographically occult vascular malformations in the brain and spine. Magnetic resonance imaging showed multiple lesions in brain and spine with hypointense areas on both T1 and T2-weighted images. These hypointense areas are usually secondary to hemosiderin deposits consistent with remote bleeding in the lesions. We conclude that when magnetic resonance reveals an intraspinal lesion with signal intensity characteristics consistent with a vascular malformation, an examination of the brain should be performed to rule out associated intracranial lesions. The finding of multiple lesions in the brain with identical signal intensity characteristics reinforces the diagnosis of vascular malformation. PMID- 1603307 TI - Pediatric craniocervical spiral CT. AB - Spiral CT, which consists of rapid volumetric data acquisition and planar image display, was performed on 100 children undergoing examinations of the brain and head and neck for a variety of clinical indications. The technique was evaluated for image quality and impact on clinical practice. Images of the brain were generally of diagnostic quality in infants and young children but not in older children, due to their larger heads and present X-ray tube current limitations. The lower contrast resolution demands in imaging head and neck structures permitted acquisition of high quality images in all age groups. The rapidity of the technique allowed vascular phase imaging with one-sixth to one quarter the amount of contrast medium injected routinely, reduced the number of artifacts related to patient motion and occasionally permitted scanning of young patients without sedation. As a consequence, the spiral technique appears to have the potential for improving the efficiency and safety of diagnostic CT in investigation of the brain, head and neck in children. PMID- 1603308 TI - Cranial CT and MRI in diseases with DNA repair defects. AB - The CT and MRI appearances of 5 patients with Cockayne's syndrome, 5 with ataxia telangiectasia and 1 with Fanconi's anaemia are reported. These conditions, together with Bloom's syndrome and xeroderma pigmentosum are regarded as disorders of DNA repair. Characteristic CT and MRI features of Cockayne's syndrome include generalised atrophy, calcification in basal ganglia and dentate nuclei and white matter low density. Neuroradiological findings in the other DNA repair disorders are nonspecific. PMID- 1603309 TI - Diagnostic role of gadolinium-DTPA in pediatric neuroradiology. A retrospective review of 655 cases. AB - We retrospectively reviewed the findings in 655 consecutive young patients who underwent contrast-enhanced MR examinations (1.5T) of the head or spine. Their ages ranged from 4 months to 20 years (mean 10 years). There was a 1.7% incidence of minor adverse reactions to gadolinium (Gd)-DTPA, none of which required treatment; no serious adverse reactions were encountered. Based on the radiologic diagnosis the patients were divided into three groups: (1) normal, (2) CNS neoplasm, (3) abnormal but not neoplasm. There were 178 patients thought to have CNS neoplasms and of these 156 (88%) enhanced. Of 124 histologically confirmed neoplasms 115 (93%) showed enhancement after Gd-DTPA. Eight children had histologically confirmed spinal neoplasms; 5 of 6 neurofibromas and 2 ependymomas enhanced. In the 216 patients with abnormalities thought not to be neoplastic, the enhancement rate was 11%; most of the enhancing lesions were vascular malformations. There were very few examples of inflammatory disease, acute trauma or stroke among our patients. PMID- 1603310 TI - Patterns of lesions of corpus callosum in inner cerebral trauma visualized by computed tomography. AB - Computed tomographic analysis of lesions of the corpus callosum in 13 patients with "inner cerebral trauma" showed significant congruence of linear translation of acceleration and the topographic distribution of such lesions. This congruence permits computed tomography to be used to reconstruct the course of linear translation and the site of the main blow, which can be important for forensic use. The findings of even a small lesion in the corpus callosum indicates the need for further investigation of other structures which are usually involved in inner cerebral trauma, such as the hippocampus and brain stem. PMID- 1603311 TI - Metastases to the pituitary--hypothalamic axis. An MR study of 7 symptomatic patients. AB - Seven patients with metastatic tumour in the pituitary-hypothalamic axis were investigated by MRI. The main clinical problems were diabetes insipidus (5 cases) and general pituitary dysfunction (2 cases). No patient had visual or oculomotor symptoms. In 6 of the 7 patients the primary malignant tumour was known, but no patient had symptoms from the primary tumour; 1 had symptoms from metastases in locations other than the pituitary gland. In one patient no primary tumour was known. MR detection of a second, clinically silent, 5 mm lesion in the posterior cranial fossa initiated the search for primary tumour. MRI showed purely suprasellar tumours in 3 patients and intra- and suprasellar tumours in 4. The latter were dumbbell lesions with only a small bridge of tissue connecting the intra- und suprasellar portions. Six of the 7 suprasellar tumours seemed to be in the infundibular recess of the third ventricle; in 5 the infundibulum was visible as an enhancing linear structure at the postero-inferior border of the tumour. The pituitary fossa was normal in all cases. PMID- 1603312 TI - Experimental focal cerebral ischaemia assessed with IVIM*-MRI in the acute phase at 0.5 tesla. AB - Intravoxel incoherent motion (IVIM*)-MRI has been performed on a clinical system at 0.5 tesla with a b gradient factor of 100 s/mm2, in a feline focal model of cerebral ischaemia. Images were obtained in 26 cats from less than 1 hour and up to 7-12 hours after stroke. The apparent diffusion coefficient (ADC) was decreased at the site of injury when compared to the contralateral normal side, by 30% in the first, 33% in 1-2 h and 27% in 2-4 h; it increased at 7-12 h, when vasogenic oedema occurred. IVIM*-MRI demonstrated early changes, due to cytotoxic oedema, during the acute phase of cerebral ischaemia to which conventional T2 weighted spin-echo imaging was not sensitive. PMID- 1603313 TI - Transient global amnesia after cerebral angiography with iohexol. AB - We describe a patient without a previous history of migraine or epilepsy and with no known vascular risk factors, who suffered subarachnoid haemorrhage. During vertebral angiography using nonionic contrast medium (iohexol), spasm of the basilar artery was seen. The patient suffered transient global amnesia. Angiography 3 months later with the same contrast medium was normal and produced no further deficit. This case lends support to the supposed ischaemic aetiology of transient global amnesia; in patients without other evidence of cerebrovascular disease, arterial spasm may be responsible. PMID- 1603314 TI - Magnetic resonance imaging of acoustic neuromas: pitfalls and differential diagnosis. AB - A total of 162 patients with suspected acoustic neuromas underwent MR imaging at 1.5 T. All patients were injected with Gd DTPA or DOTA. In 72 patients, uni- or bilateral acoustic neuromas were detected. 18 cases were equivocal: In 9 cases, contrast enhancement was due to other tumors (5 meningiomas, 2 metastases, 1 hemangioma). In 1 case, misinterpretation resulted from partial volume effects with the petrous bone marrow. In one patient, previously operated on, increased signal was due to postoperative fat graft. Four hypersignals were due to intracanalicular venous or meningeal enhancement. Three cases are still equivocal. Most of the diagnostic problems may be obviated by precontrast MR imaging, multidimensional 3-mm sections, and fast imaging. PMID- 1603315 TI - Multiple sclerosis masquerading as a mass lesion. AB - Six patients presenting with new neurological deficits underwent magnetic resonance imaging (MRI) that displayed mass lesions leading to diagnoses of tumor or abscess. Biopsy revealed demyelinating lesions. PMID- 1603316 TI - Lethal midline granuloma: impact of imaging studies on the investigation and management of destructive mid facial disease in 13 patients. AB - In 13 patients presenting as lethal midline granuloma (LMG), computed tomography proved essential for determining the extent of the disease, guiding biopsy and planning radiotherapy. Magnetic resonance imaging (MRI) was also helpful for the latter, because it could distinguish fluid retained within the paranasal sinuses from solid masses and tumour from granulation tissue; it was of little value for detecting bone lysis. Eight of the 13 patients proved to have T-cell lymphoma, two had Crohn's disease, in one the lesion was factitious and two had granulomas without diagnostic histological features. PMID- 1603317 TI - MRI changes in embolized meningiomas. AB - Study of the MRI changes that occur after superselective embolization of hypervascular meningiomas with Gelfoam powder (5 cases) and polyvinyl alcohol (PVA) particles 150-250 microns in size (4 cases) has indicated that, after embolization, meningiomas showed loss of the signal void, decrease in gadolinium DTPA contrast enhancement, and prolonged T1 and T2. Shortening of T1 and T2 was seen in two patients with Gelfoam-embolized meningiomas in whom CT showed pooling of iodinated contrast medium in the tissue. In vitro experimental data demonstrated that the shortening of T1 and T2 was due to the iodinated contrast medium. PMID- 1603318 TI - The first description and introduction into clinical use of air encephalography. PMID- 1603319 TI - Acute traumatic central cord syndrome: MRI-pathological correlations. AB - The acute traumatic central cord syndrome (ATCCS) is commonly stated to result from an injury which affects primarily the center of the spinal cord and is frequently hemorrhagic. To test the validity of this widely disseminated hypothesis, the magnetic resonance images [MRI] of 11 consecutive cases of ATCCS caused by closed injury to the spine were analyzed and correlated with the gross pathological and histological features of 3 cervical spinal cords obtained at post mortem from patients with ATCCS, including 2 of patients studied by MRI. The MRI studies were performed acutely (18 h to 2 days after injury) in 7 patients and subacutely (3-10 days after injury) in 4. Ten of the 11 patients had pre existing spondylosis and/or canal stenosis. The 11th suffered a cervical fracture. All patients exhibited hyperintense signal within the parenchyma of the cervical spinal cord on gradient echo MRI. None showed MRI features characteristic of hemorrhage on T1-weighted spin echo or T2-weighted gradient echo studies. Gross and histological examination of the necropsy specimens showed no evidence of blood or blood products within the cord parenchyma: the primary finding was diffuse disruption of axons, especially within the lateral columns of the cervical cord in the region occupied by the corticospinal tracts. The central gray matter was intact. In patients with ATCCS, the predominant loss of motor function in the distal muscles of the upper limbs may reflect the importance of the corticospinal tract for hand and finger function in the primate. In this study, the MRI and pathological observations indicate that ATCCS is predominantly a white matter injury and that intramedullary hemorrhage is not a necessary feature of the syndrome; indeed, it is probably an uncommon event in ATCCS. We suggest that the most common mechanism of injury in ATCCS may be direct compression of the cervical spinal cord by buckling of the ligamenta flava into an already narrowed cervical spinal canal; this would explain the predominance of axonal injury in the white matter of the lateral columns. PMID- 1603320 TI - MRI of spontaneous spinal cord infarction: serial changes in gadolinium-DTPA enhancement. AB - Spinal cord infarcts are rare. We report serial MRI studies of a patient with a clinically diagnosed spontaneous spinal cord infarct. The usefulness of gadolinium diethylenetriaminepentaacetic acid-dimeglumine (Gd-DTPA) enhancement is also discussed. Serial MRI with Gd-DTPA is useful to diagnose the spinal cord infarction. PMID- 1603321 TI - Signal intensity correlation of MRI with pathological findings in spinal neurinomas. AB - MR signal intensities at 0.282 T were correlated with the pathological findings in 23 cases of spinal neurinoma. With T2-weighted images (SE-T2WI or RARE-T2WI), all the tumors displayed high signal intensities similar to that of cerebrospinal fluid, indicating long T2 values. It is shown that the long T2 values of neurinomas are caused not only by intratumoral cystic formation, as reported by other authors, but also by intratumoral Antoni B structure, intratumoral micronecrosis and intratumoral vascular malformation. On SE-T1WI, the majority of neurinomas (73.9%) were isointense to spinal cord while the minority (26.1%) were hypointense. The similarity of the T1 values of neurinomas to that of the spinal cord may be related to the abundance of Schwann cells within the tumors, but tumors hypointense to cord and tumors isointense to cord on T1WI showed no significant difference in their gross and microscopic pathology. PMID- 1603322 TI - Why run parallel fibers parallel? Teleostean Purkinje cells as possible coincidence detectors, in a timing device subserving spatial coding of temporal differences. AB - The present paper explores the possible functional significance of the parallel orientation of parallel fibers in teleostean cerebellar and cerebelloid molecular layers, taking advantage of the restricted width of these molecular layers compared with mammalian ones and several specific configurations of granule cells. These configurations include: (i) a unilateral location, i.e. at only one (lateral) side of the molecular layer, giving rise to parallel fibers without bifurcation in a unidirectional molecular layer, where all parallel fibers conduct signals in the same direction; (ii) a bilateral location at both sides of the molecular layer giving rise to a bidirectional molecular layer where parallel fibers conduct signals in two opposite directions originating from two discrete sources; and (iii) a basal (or sometimes apical) location underneath (or opposite to) the layer of Purkinje cells, giving rise to a bidirectional molecular layer where parallel fibers conduct signals in two opposite directions originating from a continuous range of sources. It is argued that molecular layers with a bilateral location of granule cells, exemplified by the mormyrid lobus transitorius, represent an optimal configuration for the analysis of small temporal differences (up to 4 ms) between inputs to the right and left granule cell mass, by means of detection of the site of coincidence of parallel fiber activity running from left to right and vice versa. Morphological aspects that probably optimize such a function include not only the parallel course and bilateral origin of parallel fibers, but also their small diameter, large number and co-extensive location, as well as the sagittal orientation and the presence of many spines of Purkinje cell dendrites and the presence of stellate and other inhibitory interneurons. The only assumption underlying the present coincidence detection hypothesis is that Purkinje cells are supposed to be maximally stimulated by parallel fiber input when all spines are activated in such a way that their excitatory postsynaptic potentials reach the axon hillock simultaneously. For molecular layers with a unilateral location of granule cells, exemplified by the teleostean torus longitudinalis-tectal marginal parallel fiber system, a similar coincidence detecting mechanism is proposed on the basis of the presence of two populations of parallel fibers with slightly different conduction velocities. Such a system might be suitable to adapt the location of coincidence peaks to topographic maps present in deeper layers of nervous tissue. Molecular layers with basally (or apically) located granule cells as encountered in the teleostean corpus cerebelli, are probably involved in the analysis of specific spatio-temporal input waves directed centripetally towards different Purkinje cells.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1603323 TI - Induction of immediate early gene encoded proteins in the rat hippocampus after bicuculline-induced seizures: differential expression of KROX-24, FOS and JUN proteins. AB - Immunocytochemistry with specific antisera was used to assess regional levels of six immediate early gene encoded proteins (KROX-24, c-FOS, FOS B, c-JUN, JUN B and JUN D) in the rat hippocampus after 15 min of bicuculline-induced seizures. Serial sections of the dorsal hippocampus were examined at various postictal recovery periods up to 24 h. The results demonstrate a complex temporal and spatial pattern of immediate early gene synthesis and accumulation. Three major categories of immediate early gene products could best be distinguished in the dentate gyrus: KROX-24 and c-FOS showed a concurrent rapid rise with peak levels at 2 h and a return to baseline levels within 8 h after seizure termination. FOS B, c-JUN and JUN B levels increased more gradually with peak intensities in the dentate gyrus reached at 4 h. These immediate early gene products showed above normal levels in various hippocampal subpopulations up to 24 h. JUN D exhibited the most delayed onset combined with a prolonged increase of seizure-induced immunoreactivity. Irrespective of this differential temporal expression profile of individual transcription factors, the sequence of induction in the hippocampal subpopulations was identical for all immediate early gene-encoded proteins examined: first in the dentate gyrus granule cells followed by CA1 and CA3 neurons, respectively. Our data indicate an asynchronous synthesis of several immediate early gene-encoded proteins in the brain after status epilepticus. FOS and JUN proteins act via homo- or heterodimer complexes at the AP-1 and other DNA binding sites. The different time-courses for individual immediate early gene products strongly suggest, that at different time-points after status epilepticus, different AP-1 complexes are effective. In vitro studies have shown that different AP-1 complexes possess different DNA binding affinities as well as different transcriptional regulatory effects. Our results suggest that these molecular mechanisms are also effective in vivo. PMID- 1603324 TI - Arousal-dependent properties of medial septal neurons in the unanesthetized rat. AB - We have performed a qualitative and quantitative analysis of the electrophysiological properties of medial septal neurons in the unanesthetized rat. The rat's head was held in a stereotaxic apparatus by a painless head restrained system that was implanted seven days prior to the recording sessions. Extracellular recordings were made in a mixed population of antidromically identified septohippocampal neurons and unidentified medial septal neurons in different states of arousal and in response to peripheral and reticular stimulations. The spontaneous activity as well as the percentage of rhythmically bursting septal neurons varied significantly according to the state of arousal. Higher values were noted in paradoxical sleep (28 imp/s and 94% of bursting neurons) as compared with wakefulness with hippocampal theta rhythm (17.4 imp/s and 64.2% of bursting neurons) and slow wave sleep (12.3 imp/s and 8% of bursting neurons). The frequency of the bursts was significantly higher during paradoxical sleep. In individual medial septal neurons, arousing stimuli and paradoxical sleep could induce rhythmic bursting activity in previously non-bursting neurons provided that they were fast-firing neurons. No differences were noted in the functional characteristics of neurons in the medial septal nucleus as compared with the diagonal band of Broca. When the unanesthetized rats were compared with a group of urethane-anesthetized rats, the spontaneous activity was higher and more irregular in the absence of anesthesia. The percentage of the bursting neurons was significantly lower in the unanesthetized rats (32.3% vs 43.3%). However, the frequency of the bursts was higher (5.9 +/- 0.1 Hz vs 3.5 +/- 0.1 Hz). Since the patterns of activity of medial septal neurons fluctuate in different physiologically relevant states, previous classifications of these neurons made by ourselves and other authors, in urethane-anesthetized rats, may not be appropriate. PMID- 1603325 TI - Turnover of resident microglia in the normal adult mouse brain. AB - We undertook this study to determine whether the microglia, the resident macrophages of the central nervous system, turn over in the steady-state. The turnover of brain macrophages would lend support to the "Trojan Horse" hypothesis of central nervous system infection, since one origin of replacement cells is the circulating monocyte pool. We combined the immunohistochemical detection of F4/80, a specific macrophage marker, with [3H]thymidine incorporation and autoradiography in normal adult mice. We could detect double-labelled cells in the brains of mice perfused 60 min after isotope administration. Such cells were few in number, randomly scattered throughout the brain and had the morphology of typical resident cells. The labelling index at this survival time was 0.052 +/- 0.003%. Thus resident microglia can synthesise DNA in situ. After longer survival times, we detected larger numbers of double-labelled cells. F4/80+ cells with resident morphology, mitotic figures, pairs of closely apposed (daughter) cells and cells with rounded macrophage-like morphology, all exhibited silver labelling. Twenty-four hours after isotope administration the labelling index was 0.192 +/- 0.052%. From morphologic evidence and comparison of labelling indices at different survival times, we concluded that: (i) resident microglia can synthesise DNA and go on to divide in situ; (ii) cells are recruited from the circulating monocyte pool through an intact blood-brain barrier and rapidly differentiate into resident microglia. We estimate that the two processes contribute almost equally to the steady-state turnover of resident microglia. PMID- 1603326 TI - Autoradiographic determination of glucose content and estimation of the lumped constant in intracerebral neuronal tissue transplants. AB - The quasi-steady-state distribution volume of brain glucose was measured using 3 O-[14C]methylglucose quantitative autoradiography in a group of rats (n = 5) which 12-15 weeks previously had undergone unilateral ibotenic acid-induced lesion of the nucleus basalis magnocellularis, followed by implantation into ipsilateral neocortex of primordial basal forebrain cell suspensions. The effects of the lesion and the presence of transplanted tissue in neocortex were visualized by acetylcholinesterase histochemistry. The 3-O-[14C]methylglucose tracer was distributed homogeneously throughout the host brain areas analysed, with no side-to-side differences, despite a marked unilateral depletion of acetylcholinesterase activity ipsilateral to the lesion site. Whilst the transplants were indistinguishable from the homogeneity of surrounding host frontal cortex, there was a 70% increase in the apparent distribution volume of methylglucose localized around the ibotenate injection site and associated needle tract. Brain glucose content is an important experimental variable affecting the lumped constant of the 2-deoxyglucose technique. There was no evidence of any significant difference in the lumped constant between transplant and host tissue which might compromise the validity of the 2-deoxyglucose technique when used together with intracerebral implantation of fetal neuronal cell suspensions. PMID- 1603327 TI - Sub-populations of pars compacta neurons in the substantia nigra: the significance of qualitatively and quantitatively distinct conductances. AB - In the substantia nigra pars compacta neurons can be classified in two sub populations. In this study the distinguishing criteria have been the presence of four distinct calcium-dependent potentials, two each generated selectively and exclusively in each cell type. One class of cells, found in the more caudal pars compacta, displays calcium-mediated, slow oscillatory potentials which occur spontaneously and generate long-duration afterhyperpolarizations. A second, much faster calcium spike can be evoked after the blockade of sodium and potassium channels. This spike has a high generation threshold and is followed by a fast afterhyperpolarization. The other group of neurons is distributed principally in the rostral substantia nigra, at the level of the mammilary bodies. In these cells, a low-threshold calcium spike is generated that (i) inactivates at depolarized potentials, (ii) has no active negative phase, and (iii) causes burst firing action potentials. In all these three respects, this transient differs from the slow oscillatory potential in the more caudal group of neurons. In addition, a short-duration calcium-dependent potential can be evoked at a high threshold. Both the low- and high-threshold spikes of the rostral cells are attenuated in experiments where dendrites have been sectioned prior to the recording. The membrane properties of the caudal cell group, including the fast calcium spike, are unaffected by dendritic sectioning. It is suggested that in the guinea-pig the calcium conductances in the caudal neurons operate in or near the cell body and might play a large (though not necessarily exclusive) role in regulating autorhythmicity. In the more rostral cells, the characteristics of their particular calcium conductances which seem to be located more distally would prompt a mediating function in the secretion, and subsequent action, of neuroactive substances from dendrites. PMID- 1603328 TI - Amphetamine regulation of acetylcholine and gamma-aminobutyric acid in nucleus accumbens. AB - In situ hybridization histochemistry and in vivo microdialysis were combined to study the effect of amphetamine on the expression of choline acetyltransferase and glutamate decarboxylase67 mRNA and in vivo release of acetylcholine and GABA in rat medial nucleus accumbens. Differential effects on acetylcholine and GABA neurons by a single challenge injection of amphetamine (1.5 mg/kg, s.c.) were apparent in saline-pretreated and amphetamine-pretreated (same dose, twice daily for the previous seven days) rats. Extracellular acetylcholine levels were increased up to 50% over a prolonged period following both single and repeated amphetamine. In contrast, extracellular concentrations of GABA were gradually decreased to half the control values, but only in rats receiving repeated amphetamine. Although the increase of acetylcholine release was not associated with any change in choline acetyltransferase mRNA levels, the number of neurons expressing high levels of glutamate decarboxylase67 mRNA was decreased (28%) following repeated injections. Thus we suggest that amphetamine decreases extracellular GABA levels by a slow mechanism, associated with the decreased expression of glutamate decarboxylase67 mRNA in a subpopulation of densely labeled neurons in the medial nucleus accumbens. The delayed response by GABA to amphetamine may reflect supersensitivity in the activity of postsynaptic gamma aminobutyric acid-containing neurons in nucleus accumbens as a consequence of the repeated amphetamine treatment. PMID- 1603329 TI - Calcitonin gene-related peptide in rat spinal cord motoneurons: subcellular distribution and changes induced by axotomy. AB - Using light and electron microscopy, a study has been made of the changes of calcitonin gene-related peptide-like immunoreactivity in rat lumbar spinal cord motoneurons during cell body response to sciatic nerve injury. At light microscopy level, calcitonin gene-related peptide-like immunoreactivity was evaluated using an indirect immunofluorescence technique combined with Fast Blue retrograde tracing and a peroxidase-antiperoxidase procedure. The calcitonin gene related peptide changes to sciatic nerve transection and crushing were compared. Calcitonin gene-related peptide-like immunoreactivity was transiently increased after the peripheral nerve lesion, but the response was sustained for a longer period when the peripheral nerve was transected and nerve regeneration prevented. The first changes in calcitonin gene-related peptide-like immunoreactivity were detected four days after nerve crush or transection. In animal spinal cords to which nerve crush had been applied, the maximal enhancement of immunoreactivity was found 11 days after lesion. This was followed by a gradual decline, normal levels being attained 45 days after nerve crushing. When the nerve was transected, the response was similar, but the maximal calcitonin gene-related peptide-like immunoreactivity was maintained over a period of between 11 and 30 days. As with crushing, an important decrease was observed after 45 days. The ultrastructural compartmentation of calcitonin gene-related peptide-like immunoreactivity was studied using either peroxidase-antiperoxidase method or immunogold labelling. Calcitonin gene-related peptide-like immuno-reactivity was located in restricted sacs of the Golgi complex, multivesicular bodies, small vesicles and tubulo-vesicular structures. Large, strongly labelled vesicles resembling secretory granules were also observed in neuronal bodies. Our results reveal that the increase of calcitonin gene-related peptide in motoneurons is a relevant change the cell body undergoes in response to peripheral injury. The ultrastructural location of the peptide distribution suggests specific compartmentation on tubulo-vesicular structures connected with the Golgi complex which form a network in the neuronal cytoplasm. The distribution pattern observed may be related to the sorting and delivery of calcitonin gene-related peptide to secretory vesicles. PMID- 1603330 TI - Gene expression and localization of opioid peptides in immune cells of inflamed tissue: functional role in antinociception. AB - Our previous studies indicate that endogenous opioids (primarily beta-endorphin) released during stressful stimuli can interact with peripheral opioid receptors to inhibit nociception in inflamed tissue of rats. This study sought to localize opioid precursor mRNAs and opioid peptides deriving therefrom in inflamed tissue, identify opioid containing cells and demonstrate their functional significance in the inhibition of nociception. In rats with Freund's adjuvant-induced unilateral hindpaw inflammation we show that: (i) pro-opiomelanocortin and proenkephalin mRNAs (but not prodynorphin mRNA) are abundant in cells of inflamed, but absent in non-inflamed tissue; (ii) numerous cells infiltrating the inflamed subcutaneous tissue are stained intensely with beta-endorphin and [Met]enkephalin (but only few scattered cells with dynorphin) antibodies; (iii) beta-endorphin is present in T- and B-lymphocytes, monocytes and macrophages; and (iv) whole-body irradiation suppresses stress-induced antinociception in the inflamed paw. Taken together, these data suggest that endogenous opioid peptides are synthesized and processed within various types of immune cells at the site of inflammation. Immunosuppression abolishes the intrinsic antinociception in inflammatory tissue confirming the functional significance of these cells. PMID- 1603331 TI - Potentiated expression of FOS protein in the rat spinal cord following bilateral noxious cutaneous stimulation. AB - A noxious mechanical or chemical stimulus to the ventral skin of one hindpaw induced the expression of FOS proteins ipsilaterally in the spinal dorsal horn neurons in the rat. The number of FOS-labelled cells reached a maximum at 2-3 h, and decayed to basal levels within 6 h after the stimulus. When a first noxious stimulus was applied to the contralateral hindpaw 1-1.5 h prior to this stimulus, the number of FOS-labelled cells increased, over all laminae, to 153% (mechanical) and 164% (chemical) compared to the number produced by a single stimulus. This effect of a prior stimulus in increasing the number of FOS labelled cells produced by a contralateral stimulus persisted for several hours after the first stimulus. The results are interpreted as a sensitization of dorsal horn neurons induced by peripheral noxious stimuli, which is manifest at the molecular biological level. PMID- 1603332 TI - Direct and indirect actions of morphine on medullary neurons that modulate nociception. AB - The rostral ventromedial medulla is part of a neural network through which systemically administered morphine produces antinociception. Two physiologically characterized classes of presumed nociceptive modulating neurons that respond differentially to systemically administered morphine have been identified in this region: the firing of "on-cells" is depressed, whereas "off-cells" become continuously active. On-cells have been proposed to permit or facilitate, and off cells to inhibit, nociceptive transmission. Because local application of morphine in the rostral ventromedial medulla itself is sufficient to produce antinociception, it is important to determine whether systemically administered morphine exerts its effects on neurons in this region by a direct action. Thus, activity of physiologically characterized neurons was studied before, during and after ionotophoretic administration of morphine. As with systemic administration, iontophoretic application of morphine depresses the activity of on-cells, an effect that is reversed by iontophoretic as well as by systemic administration of naloxone. In contrast, no reliable changes in the firing of off-cells are produced by iontophoretic administration of morphine. Cells of a third class, "neutral cells", are not affected by systemic morphine administration, nor do they respond to iontophoretic application of the drug. The present experiments demonstrate that direct opioid responsiveness in the rostral ventromedial medulla is limited to a single physiologically characterized class of presumed nociceptive modulatory neuron, the on-cell. This implies that the antinociceptive effect exerted by systemically administered morphine involves at least two components within the rostral ventromedial medulla: a direct inhibition of on cells, and an indirect activation of off-cells. Each of these actions is likely to have a net hypoalgesic effect. PMID- 1603333 TI - Cocaine-induced conditioned locomotion: absence of associated increases in dopamine release. AB - The potent reinforcing effects of cocaine can readily become associated with salient environmental stimuli that acquire secondary reinforcing properties. This phenomenon is of considerable significance as intense craving can be evoked by stimuli previously associated with the effects of cocaine. It has been proposed that the reinforcing properties of these conditional stimuli are due to their ability to elicit neural events that are similar to those produced by the drug itself. Given the large body of evidence that implicates the mesolimbic dopaminergic projection in the unconditioned behavioural properties of cocaine, the present study used in vivo microdialysis to determine whether stimuli paired with cocaine elicit increases in interstitial dopamine in the nucleus accumbens that are similar to the unconditioned effects of this drug. When administered acutely, cocaine (10 mg/kg, i.p.) produced a potent unconditioned increase in interstitial dopamine concentrations (300% of basal values) in the nucleus accumbens. The results from two separate experiments indicate that the administration of cocaine (10 mg/kg for seven days) in association with a specific environment produced significant locomotion in that environment. Compared to subjects that received saline in both settings, rats that received cocaine in their home cage (pseudoconditioned group) did not exhibit increased locomotion on the test day. Although repeated pairing of cocaine with a specific environment produced conditioned locomotion, there was no concomitant conditional increase in dopamine release. Specifically, the modest increase in dopamine (10 15% above basal values) observed after exposure to the conditional environment was equal in the conditioned and pseudoconditioned groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603334 TI - Thymopoietin, a polypeptide ligand for the alpha-bungarotoxin binding site in brain: an autoradiographic study. AB - Thymopoietin, a 48-49-amino acid polypeptide present in the thymus gland, was investigated as a potential ligand for the neuronal nicotinic alpha-bungarotoxin binding site in rat brain. Binding of [125I]alpha-bungarotoxin to whole rat brain sections was inhibited by thymopoietin in a concentration-dependent manner with an IC50 of 30.0 +/- 8.2 nM as compared to 1.1 +/- 0.3 nM for alpha-bungarotoxin. However, at concentrations of thymopoietin of up to 1 microM, [3H]nicotine binding to high affinity sites was not inhibited. Thysplenin, a polypeptide with considerable homology to thymopoietin did not affect [125I]alpha-bungarotoxin binding. These results suggest that thymopoietin selectively interacts with the nicotinic alpha-bungarotoxin binding site labelled by [125I]alpha-bungarotoxin rather than the neuronal nicotinic receptor(s) labelled by [3H]nicotine. Autoradiographic studies revealed that 1 microM thymopoietin almost completely inhibited [125I]alpha-bungarotoxin binding in all brain regions. Computer assisted image analysis of displacement curves was performed on various brain areas rich in alpha-bungarotoxin binding, such as the dorsal endopiriform nucleus, fields 1 and 2 of Ammon's horn, the polymorph cell layer of the dentate gyrus and cortical layers 4 and 5. Thymopoietin inhibited [125I]alpha bungarotoxin binding with similar potency in all these regions, suggesting that it interacted at the same site in the different brain areas. The IC50 values averaged over the six regions were 24.6 +/- 2.8 nM for thymopoietin and 1.2 +/- 0.2 nM for alpha-bungarotoxin. These results show that thymopoietin specifically interacted with the alpha-bungarotoxin site with a similar potency in different brain regions. It is suggested that thymopoietin represents a selective ligand for alpha-bungarotoxin binding sites in brain. PMID- 1603335 TI - Morphological response of endoplasmic reticulum in cerebellar Purkinje cells to calcium deprivation. AB - Mobilisable intracellular Ca2+ stores are highly enriched in the cerebellum, particularly in Purkinje cells. We have detected, by light and electron microscopy, striking morphological changes in the presumed Ca2+ stores of Purkinje cells when slices of eight-day-old rat cerebellum were incubated in Ca(2+)-deficient media. After 30 min under these conditions, the endoplasmic reticulum became thinned and elongated. By 2 h, it was transformed into multilamellar, whorl-like inclusions with electron-dense cores. These changes were reversed on reintroduction of Ca2+. Analogous changes in other neurons were not observed. The results suggest that Ca2+ storage sites within Purkinje cells are capable of dramatic morphological change depending on the availability of Ca2+. The transformations may reflect, initially, depletion of Ca2+ from the stores and then homeostatic alterations in their capacity. PMID- 1603336 TI - Cholecystokinin: critical role in mediating olfactory influences on reproduction. AB - Our electrophysiological studies in female mice have demonstrated that electrical stimulation of the accessory olfactory bulb excites tuberoinfundibular dopaminergic arcuate neurons via the amygdala-stria terminalis route. This study shows that the medial preoptic area is identified as an additional relay for the excitatory transmission by examining the effectiveness of locally infused lignocaine anaesthetic in blocking the transmission and that of electrical stimulation in evoking a shorter latency response. Based on the known immunohistochemical findings, further attention is focused on a transmitter mediating synaptic transmission in the medial preoptic area. The cholecystokinin B type receptor antagonist L-365,260 (0.3, 0.6, 0.9 pmol), but not the A type receptor antagonist L-364,718 (0.9 pmol), infused into the medial preoptic area, blocked the excitation of tuberoinfundibular arcuate neurons in a dose-dependent manner. Conversely, cholecystokinin octapeptide (0.6 pmol) increased firing activity in such neurons. The antagonizing effect of L-365,260 was reproduced in the context of the olfactory block to pregnancy: bilateral infusions of this drug into the medical preoptic area of recently mated females immediately before exposures to strange males' pheromones prevented them from inducing pregnancy block. These findings implicate cholecystokinin acting on cholecystokinin-B receptors in the medial preoptic area as a mediator of olfactory influences on reproductive physiology. PMID- 1603337 TI - Participation of capsaicin-sensitive afferent neurons in gastric motor inhibition caused by laparotomy and intraperitoneal acid. AB - Stimulation of somatic or visceral nociceptors causes changes in gastrointestinal motor activity and blood pressure. The present study examined the possible participation of capsaicin-sensitive afferent and noradrenergic efferent neurons in the blood pressure and gastric motor responses to laparotomy and intraperitoneal injection of capsaicin or hydrochloric acid in the rat. Gastric motor activity was measured by recording the intragastric pressure of phenobarbital-anaesthetized rats via an oesophageal catheter. Laparotomy as well as intraperitoneal injection of capsaicin (33 and 330 microM) or hydrochloric acid (30 mM) caused a transient reduction of gastric motor activity stimulated by intravenous infusion of bombesin (200 pmol/min) and a brief fall of blood pressure (depressor effect). The depressor effect of laparotomy was followed by prolonged hypertension. Defunctionalization of capsaicin-sensitive afferent neurons by systemic pretreatment of rats with capsaicin (0.4 mmol/kg) prevented the depressor effect and gastric motor inhibition elicited by laparotomy, intraperitoneal capsaicin (33 microM) or intraperitoneal hydrochloric acid (30 mM). However, the effects of 330 microM capsaicin on blood pressure and gastric motility were only partially reduced by capsaicin pretreatment. Blockade of noradrenergic sympathetic neurons by pretreating rats with guanethidine (0.225 mmol/kg) prevented the gastric motor inhibition and depressor effects of laparotomy and intraperitoneal injection of hydrochloric acid (30 mM). The inhibition of gastric motility caused by capsaicin (33 and 330 microM) was only partially reduced by guanethidine pretreatment. The secondary hypertension following the depressor effect of intraperitoneal capsaicin or hydrochloric acid was enhanced in guanethidine-pretreated rats whereas the prolonged hypertension induced by laparotomy was left unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603338 TI - Calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity in endothelial cells after long-term stimulation of perivascular nerves. AB - Since both perivascular nerves and the endothelium are involved in the control of the tone of smooth muscle in the wall of blood vessels, we decided to test whether electrical stimulation of perivascular nerves might lead to structural and immunocytochemical changes in the vascular endothelium. Long-term electrical stimulation in vivo of perivascular nerves of the rabbit central ear artery was applied. The results indicate that chronic stimulation of perivascular nerves for 10 days induced structural changes and the appearance of calcitonin gene-related peptide- and neuropeptide Y-like immunoreactivity in a subpopulation of endothelial cells. PMID- 1603339 TI - What features improve the accuracy of clinical diagnosis in Parkinson's disease: a clinicopathologic study. AB - Many authorities have drawn attention to the difficulties in clinically distinguishing Parkinson's disease (PD) from other parkinsonian syndromes. We assessed the clinical features of 100 patients diagnosed prospectively by a group of consultant neurologists as having idiopathic PD according to their pathologic findings. Seventy-six percent of these cases were confirmed to have PD. By using selected criteria (asymmetrical onset, no atypical features, and no possible etiology for another parkinsonian syndrome) the proportion of true PD cases identified was increased to 93%, but 32% of pathologically confirmed cases were rejected on this basis. These observations suggest that studies based on consultant diagnosis of PD, using standard diagnostic criteria, will include cases other than PD, thus distorting results from clinical trials and epidemiologic studies. The strict use of additional criteria can reduce misdiagnosis but at the cost of excluding genuine PD cases. PMID- 1603340 TI - Therapeutic bioequivalency study of brand name versus generic carbamazepine. AB - We performed a randomized double-blind crossover therapeutic bioequivalency study of a generic (Epitol) versus a brand name (Tegretol) carbamazepine product under steady-state conditions in 40 epileptic patients. Each patient received 90-day supplies of Epitol or Tegretol and placebo, which replaced the usual dosage of the alternate product. Group A consisted of 20 seizure-free (from 5 months to 2 years) patients and group B of 20 patients with seizures refractory to drug therapy. In group A, four patients had seizures, two on both Epitol and Tegretol and two on Tegretol. In group B, the average seizure frequencies were 0.25 seizures per day on Epitol and 0.22 seizures per day on Tegretol. Average seizure frequencies were statistically the same (at a 20% difference, p less than 0.05). Areas under the curve were statistically the same (at a 20% difference, p = 0.05). Average peak heights were statistically the same (at a 20% difference, p less than 0.05). Average time to peak was earlier with Epitol. Epitol and Tegretol performed equally well in clinical efficacy and bioequivalency. PMID- 1603341 TI - Chronic limb-girdle myasthenia gravis. AB - The existence of chronic "limb-girdle" form of myasthenia gravis (MG) has been questioned. We report here 12 such patients (10 women and two men) who constituted 3.8% of 314 MG patients in our study. The duration of disease ranged from 4 months to 7 years before the diagnosis. In almost all cases, the initial diagnosis was other than MG. None of the patients had any oculobulbar weakness. Acetylcholine receptor antibody was positive in five cases, although not all in the first assay. Repetitive nerve stimulation test was positive in all cases, although not necessarily the first time. Single-fiber EMG was positive in 11 cases. All patients responded to acetylcholinesterase inhibitors, and two thirds underwent immunotherapy. Diagnosis of limb-girdle MG requires a strong index of suspicion. PMID- 1603342 TI - Chronic inflammatory demyelinating polyradiculoneuropathy: comparison of patients with and without an associated monoclonal gammopathy. AB - We reviewed our data from patients with the clinical diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Seventy patients had no demonstrable underlying disease to account for their polyneuropathy and were classified as idiopathic CIDP (CIDP-I). We detected a monoclonal gammopathy of uncertain significance (MGUS) in 30 patients who were classified as CIDP-MGUS; 17 had an IgG gammopathy, 12 an IgM gammopathy, and one an IgA gammopathy. Compared with CIDP-I patients, CIDP-MGUS patients were older and slightly more likely to be males. When compared with patients with an MGUS but without polyneuropathy reported in the literature, CIDP-MGUS patients had similar distributions of age, sex, and immunoglobulin class. There were no significant differences in motor and sensory nerve conduction measures between CIDP-I and CIDP-MGUS patients, nor between CIDP-MGUS patients with IgM and those with IgG or IgA gammopathy. Strict electrodiagnostic criteria for primary demyelination were fulfilled by 54% of CIDP-I patients and 40% of CIDP-MGUS patients, but these were not significantly different. Our study suggests that (1) the demographic features and immunoglobulin class distribution of CIDP-MGUS patients largely reflect those of patients with an MGUS, but without polyneuropathy, (2) CIDP-MGUS patients as a group cannot be distinguished from CIDP-I patients on the basis of nerve conduction studies, and (3) IgM CIDP-MGUS patients cannot be distinguished from those with other immunoglobulin classes. PMID- 1603343 TI - The Rochester Diabetic Neuropathy Study: reassessment of tests and criteria for diagnosis and staged severity. AB - We evaluated the initial assessments of the 380 diabetic patients with and without polyneuropathy in the Rochester Diabetic Neuropathy Study for (1) associations among neuropathy test results, (2) usefulness of different tests for diagnosing and staging polyneuropathy, (3) appropriateness of different minimal criteria for the diagnosis of polyneuropathy, and (4) significant differences in test results with increasing stage of polyneuropathy. Nerve conduction ([NC]; abnormality in two or more nerves) and quantitative autonomic examination ([QAE]; decreased heart-beat response to deep breathing [DB] or the Valsalva maneuver [VAL]) were the most sensitive and objective and were especially suitable for detection of subclinical neuropathy. We propose the following minimal criteria for the diagnosis of diabetic polyneuropathy: greater than or equal to 2 abnormal evaluations (from among neuropathic symptoms, neuropathic deficits, NC, quantitative sensory examination [QSE], and QAE) with one of the two being abnormality of NC or QAE (DB or VAL). Neuropathy Symptom Score, Neuropathy Disability Score, QSE (vibratory or cooling detection threshold), and summated compound muscle action potential of ulnar, peroneal, and tibial nerves were best for judging severity. Inability to walk on heels provided a discrete separation of diabetic patients into those with mild and those with more severe neuropathy- a separation helpful in staging. PMID- 1603344 TI - A human visual disorder resembling area V4 dysfunction in the monkey. AB - We surveyed a broad range of visual functions in a man who complained of abnormal color experience and inability to recognize faces following bilateral damage in the visual cortex. A lesion in his right visual cortex caused complete left visual field loss. A lesion in his left visual cortex, located entirely below the calcarine fissure, affected the vision in his remaining hemifield, the right one. Psychophysical testing showed severely defective color vision and pattern processing, but relatively normal luminance contrast detection thresholds. The finding of normal spatial contrast sensitivity and static stereopsis did not resemble a parvocellular defect of the type described in the monkey. The abilities to detect global coherent motion among noise, structure from motion and dynamic stereopsis, and to pursue moving targets showed normal motion processing at several levels. Together with normal flicker perception, these results excluded magnocellular or MT-like defects. Altogether, the findings mimic area V4 dysfunction. PMID- 1603345 TI - Numb chin syndrome in cancer patients: etiology, response to treatment, and prognostic significance. AB - We retrospectively evaluated 42 consecutive cancer patients with numb chin syndrome (NCS). Breast cancer comprised 64% of the primary tumors, and lymphoproliferative neoplasms comprised 14%. A standard workup (including imaging of the brain, base of skull, and mandible, and CSF analysis) led to the diagnosis of a metastatic etiology in 89% of the patients. Fifty percent of the patients had mandibular metastases, 14% base-of-skull bone lesions, and 22% leptomeningeal seeding. NCS was a late manifestation of malignancy, associated with disease progression in 67% of the patients or heralding a relapse, which was often confined to the leptomeninges, in 31%. Although various therapeutic strategies led to resolution of NCS, median survival after its diagnosis was 5 months when due to bone metastases and 12 months if associated with leptomeningeal seeding. PMID- 1603346 TI - Dementia after stroke: baseline frequency, risks, and clinical features in a hospitalized cohort. AB - We determined the frequency of dementia in a cohort of 251 patients aged greater than or equal to 60 years hospitalized with acute ischemic stroke, based on examinations performed 3 months after stroke onset. Using modified DSM-III-R criteria, we found dementia in 66 patients (26.3%). Diagnostic agreement among raters was excellent (kappa = 0.96). In a control sample of 249 stroke-free subjects recruited from the community and matched by age, we found dementia in eight subjects (3.2%). Using a logistic regression model to estimate the risk of dementia associated with stroke in the combined samples, the odds ratio (OR) for stroke patients compared with control subjects was 9.4 (p less than 0.001). Advancing age and fewer years of education were significant, independent correlates of dementia, with a trend evident for race (non-white versus white). Confining the analysis to subjects residing in the Washington Heights-Inwood community of northern Manhattan, the OR was 10.3 (p less than 0.001) with significant age and race effects. We conclude that ischemic stroke significantly increases the risk of dementia, with independent contributions by age, education, and race. PMID- 1603347 TI - Vasodepressor carotid sinus syncope associated with a neck mass. AB - We present the hemodynamic and autonomic features of recurrent purely vasodepressor syncope episodes in a patient with left-sided malignant cervical adenopathy involving the carotid sinus. Extreme hypotension lasting 10 to 30 minutes, without change in heart rate, occurred spontaneously and 20 seconds after head-turning. The baseline respiratory sinus arrhythmia, heart rate response to standing and Valsalva's maneuver, and cold-induced blood pressure elevation were normal, indicating normal baroreceptor function between episodes. The episodes abated after 1 week of bedrest but reappeared within 1 day of discharge from the hospital. Syncope no longer occurred after intracranial section of the left glossopharyngeal nerve and upper rootlets of the left vagus. Autonomic testing remained normal postoperatively. A review of the literature indicates that purely vasodepressor syncope has been more common with left carotid sinus lesions. PMID- 1603348 TI - 31P NMR spectroscopy and ergometer exercise test as evidence for muscle oxidative performance improvement with coenzyme Q in mitochondrial myopathies. AB - Two patients with mitochondrial encephalomyopathy due to complexes I and IV deficiencies received 150 mg/d of coenzyme Q10 (CoQ). We studied them with a bicycle ergometer exercise test and 31P NMR spectroscopy before and after 10 months of treatment. Before treatment, we observed a low phosphocreatine/inorganic phosphate (PCr/P(i)) resting value along with abnormally high resting lactate concentration. During exercise, there was a pronounced acidosis with delayed kinetics of postexercise recovery for blood lactate, pH, PCr, and PCr/P(i) ratio. Oxygen uptake during exercise was reduced while the lowering of the ventilatory threshold indicated an early activation of glycolysis. After treatment, the bicycle ergometer exercise test indicated a significant improvement with a decrease in resting blood lactate level, an increase in oxygen consumption during exercise, and an increase in the kinetics of lactate disappearance during the recovery period. A shift of the ventilatory threshold to higher workload was present. 31P NMR spectroscopy confirmed the improvement, showing a significant increase in the PCr/P(i) ratio at rest and in the kinetics of recovery for pH, PCr, and PCr/P(i) ratio following exercise in patient 1. For patient 2, we observed a less pronounced acidosis correlated with a lesser amount of Pi produced during exercise. These observations indicate an improvement of mitochondrial function and a shift from high to low glycolytic activity in both patients consequent to CoQ treatment. PMID- 1603349 TI - Abnormal brain and muscle energy metabolism shown by 31P magnetic resonance spectroscopy in patients affected by migraine with aura. AB - We studied brain and muscle energy metabolism by phosphorus 31 magnetic resonance spectroscopy (31P-MRS) in 12 patients affected by migraine with aura (classic migraine) in interictal periods. Brain 31P-MRS disclosed a low phosphocreatine content in all patients, accompanied by high adenosine diphosphate concentration, a high percentage of V/Vmax (adenosine triphosphate), and a low phosphorylation potential--features showing an unstable state of metabolism in classic migraine. Abnormal muscle mitochondrial function, in the absence of clinical signs of muscle impairment, was present in nine of the 12 patients examined. PMID- 1603350 TI - Wolfram syndrome: evidence of a diffuse neurodegenerative disease by magnetic resonance imaging. AB - Wolfram syndrome is an autosomal recessive disorder beginning in childhood that consists of four cardinal features: optic atrophy, diabetes mellitus, diabetes insipidus, and neurosensory hearing loss. Aside from these features, the clinical picture is highly variable and may include other neurologic abnormalities such as ataxia, nystagmus, mental retardation, and seizures. We present two unrelated patients with Wolfram syndrome, both of whom had the four cardinal features and several other neurologic abnormalities. MRIs showed widespread atrophic changes throughout the brain, some of which correlated with the major neurologic features of the syndrome. PMID- 1603351 TI - Symptomatic and nonsymptomatic headaches in a general population. AB - We assessed the lifetime prevalences of headache disorders in a cross-sectional epidemiologic survey of a representative 25- to 64-year-old general population. We classified the headaches on the basis of a clinical interview and a physical and neurologic examination using the operational diagnostic criteria of the International Headache Society. Lifetime prevalence of idiopathic stabbing headache was 2%, of external compression headache 4%, and of cold stimulus headache 15%. Benign cough headache, benign exertional headache, and headache associated with sexual activity each occurred in 1%. Lifetime prevalence of hangover headache was 72%, of fever headache 63%, and of headache associated with disorders of nose or sinuses 15%. Headaches associated with severe structural lesions were rare. External compression headache, fever headache, headache associated with metabolic disorders, and headache associated with disorders of nose or sinuses all showed significant female preponderance. The symptomatic headaches and headaches unassociated with structural lesions were more prevalent among migraineurs. In subjects with tension-type headache, only hangover headache was overrepresented. There was no association between the headache disorders and abnormal routine blood chemistry or arterial hypertension. In women with migraine, however, diastolic blood pressure was significantly higher than in women without migraine. PMID- 1603352 TI - Comparison of cisternal and lumbar CSF examination in leptomeningeal metastasis. AB - We compared cisternal and lumbar CSF examination in 14 patients suspected of having leptomeningeal metastasis from cancer. Malignant cells were present in 12 patients--in both cisternal and lumbar CSF in nine patients and only in cisternal CSF in three. Cisternal CSF cytologic examination should be considered in patients suspected of having leptomeningeal metastasis if lumbar CSF is nondiagnostic. PMID- 1603353 TI - Oligoclonal immunoglobulin D in the cerebrospinal fluid of neurologic patients. AB - Oligoclonal immunoglobulin D (IgD) bands were observed in 20 of 110 CSF samples investigated by our method for isoelectric focusing (IEF) of IgD in unconcentrated CSF. These were mostly from demyelinating disorders, viral CNS infections, and CNS tumors. The patterns of expression of IgD were similar to that of IgG, except in cases with tumors where oligoclonal IgD may occur independently of IgG. The study shows for the first time the presence of oligoclonal IgD in CSF from neurologic patients. PMID- 1603354 TI - CIDP masquerading as uremic polyneuropathy. PMID- 1603355 TI - Spinal epidural lipomatosis in Cushing's syndrome secondary to an adrenal tumor. PMID- 1603356 TI - Zidovudine myopathy. PMID- 1603357 TI - Fetal akinesia deformation. PMID- 1603358 TI - Sinus thrombosis. PMID- 1603359 TI - Homocystinuria. PMID- 1603360 TI - Complex I and movement disorders. PMID- 1603361 TI - Cluster headache in twins. PMID- 1603362 TI - Complications of venous catheterization. PMID- 1603363 TI - Closing USUHS. PMID- 1603364 TI - Who should handle triage? PMID- 1603365 TI - Who should handle triage? PMID- 1603366 TI - Invasive pressure monitoring in combat medical facilities: a plea for sophistication. PMID- 1603367 TI - Epidemic keratoconjunctivitis. PMID- 1603368 TI - Endocervical cell recovery. AB - Three thousand six hundred fourteen Papanicolaou smear reports were evaluated for endocervical cells and characteristics of the patients at the time the slide was taken. Differences were found related to the age of the patient, pregnancy/postpartum status, and cytology. The use of hormones when the smear was taken did not appear to affect the presence of endocervical cells. Many clinicians, believing that not obtaining endocervical cells results from failure to sample the endocervical canal, repeat those smears. This study is consistent with previous ones in finding that other factors, including patient characteristics, have a definite effect on the results. Repeating smears solely for lack of endocervical cells does not appear to be warranted for either the patient or the provider. PMID- 1603369 TI - Prehospital care and the military. AB - Significant evolution has occurred in prehospital care over the past decade. Civilian emergency medical service (EMS) systems have become progressively sophisticated. Military systems have tended to maintain a wartime philosophy toward prehospital care, and thus its peacetime ambulance service, at times, is not prepared to provide the same standard of care given by the civilian community. This article reviews the current status of civilian and military EMS and attempts to put in perspective the directions that the military could go to improve on the prehospital care it provides. PMID- 1603370 TI - Photographic cockpit model for prescribing multifocals. AB - Recent interest in the relevancy of near vision tests for presbyopic aircrew members has led to the development of a photographic cockpit model. This model is used to prescribe more accurately for flying personnel. Prescriptions can be evaluated by use of trial lenses. This allows the aircrew members to experience the effect of viewing instruments in the cockpit of a C-130 aircraft. PMID- 1603371 TI - The incidence of permanent upper and lower extremity profiles in active duty Army officers. AB - The records of 89,955 active duty Army officers were reviewed to determine their incidence of permanent upper and lower extremity profiles. Only 1,706 officers (1.897%) have permanent upper or lower extremity profiles. However, the incidence of such profiles varies with respect to rank, branch, and sex. Some officer groups have an incidence as high as 37%. Although the overall incidence of such profiles is quite low, the dramatically increased incidence in some officer groups demands scrutiny. PMID- 1603372 TI - Case study: the implementation of total quality management at the Charleston VA Medical Center's Dental Service. AB - Total Quality Management (TQM) is an evolving management philosophy which has recently been introduced to the health care industry. TQM requires the use of a continuous process improvement methodology for delivered services. It was implemented at Charleston VAMC's Dental Service as a study to determine its effectiveness at the grassroots level. A modified Quality Circle was established within the clinical service under the guidance of Dr. Edward Deming's 14 principles. Top management support was not present. Many lessons were learned as process improvements were made. The overall success was limited due to the inability to address interdepartment process problems. PMID- 1603373 TI - An assessment of pre- and post-fitness measures in two remedial conditioning programs. AB - The purpose of this study was to determine if taking part in a command-organized remedial physical condition program based on the OPNAVINST 6110.1 Basic Exercise Program (BEP) is effective in reducing body fat, improving failure-specific performance on components of the Physical Readiness Test (PRT), and improving overall physical fitness level. Pre- and post-program PRT results collected for participants in two BEP-based remedial programs showed trends toward improvement in performance on the curl-ups, push-ups, and run/walk tests as well as a positive change in overall classification scores and percent of participants passing the follow-up PRT. A substantive impact on body fat reduction was not demonstrated. PMID- 1603374 TI - Utilization of an oral pathology service: a professional responsibility. AB - The role of oral pathologists as members of the comprehensive health care team is reviewed. The importance of utilizing an Oral Pathology Service in the everyday practice of dentistry and medicine and the inherent medicolegal considerations are discussed. Standards of care for submission of surgically removed oral tissues is an issue that warrants further delineation. PMID- 1603375 TI - Factors influencing confirmed drug positives for Navy and Marine Corps recruits. AB - Confirmed use of marijuana and cocaine in Navy and Marine Corps recruit populations was examined in terms of age, month of enlistment, recruit class size, education level, and Armed Forces Qualifications Test (AFQT) scores. Between 1982 and 1989, confirmed use of the drugs showed a seasonal variation, with the highest levels in the fall and winter. The rate for marijuana and cocaine was inversely related to the size of the recruit class (r = -0.80) and completion of high school (r = -0.82). The recruit class is larger and younger in the summer. AFQT scores were directly related to age. Education level appears to be one major determinant in addressing drug use. PMID- 1603376 TI - Report on Gardnerella vaginitis. AB - Gardnerella vaginitis is one of the most common diagnoses in our outpatient clinic. From January 1, 1989 through July 30, 1989 we had 230 positive cultures for G. vaginitis. Eighty-three compliant patients in this group had unabated symptoms with documented positive cultures for Gardnerella after treatment with metronidazole. This led to the use of alternative regimens of ceftriaxone or clindamycin. A survey of antibiotic choice and post-treatment culture obtained 103 entries from 34 active duty women soldiers and 60 women dependents. This paper presents the results of the survey after an introduction beginning with a 1953 article in U.S. Armed Forces Medical Journal. PMID- 1603377 TI - Treatment of malaria acquired in Southeast Asia. PMID- 1603378 TI - The Department of Defense Civilian External Peer Review Program: an interim report. AB - During a 2-year period (December 1987-December 1989), 165 Department of Defense (DoD) military hospitals world-wide provided 71,800 cases with 83,197 reviews for quality of care evaluations by the Civilian External Peer Review Program (CEPRP). The majority (78,246 of 79,896) of completed peer review determinations (97.9%) generated agreement with care and documentation. It is concluded that health care in military treatment facilities is of high quality, meeting and generally exceeding accepted standards of care. It is also concluded that the DoD CEPRP offers conceptual and practical experience to guide the further evolution and integration of clinical peer review and quality improvement activities. PMID- 1603379 TI - Medication refusal by psychiatric inpatients in the military. AB - Military psychiatrists must occasionally treat mentally ill active duty patients who refuse medications. Unlike their civilian counterparts, military psychiatrists have no established procedure to allow for involuntary treatment under non-emergency conditions. The following case and discussion is presented to illustrate how existing guidelines do not allow for optimal care of some of these patients. PMID- 1603380 TI - Podiatric utilization referral patterns at an Army medical center. AB - Presented is the first descriptive data on a large military Podiatry Clinic supporting largely combat troops. Data consist of initial podiatric problems of soldiers and other beneficiaries of podiatric care. Demographic, physician referral patterns, and other pertinent summarized survey information of outpatient utilization at the Podiatry Clinic, Madigan Army Medical Center, Fort Lewis, Washington, are examined. Findings are based on new and initial consult referrals from the month of November 1988. The results indicated that some clinics needed inservices and further education concerning podiatric care. This study has led to the implementation of changes which have resulted in better and more timely patient care. PMID- 1603381 TI - Defense Health Agency. PMID- 1603382 TI - Who should command? PMID- 1603383 TI - Gross hematuria as a presenting symptom of disseminated gonorrhea. AB - I report a case of disseminated gonorrhea which presented with macrohematuria, a heretofore unreported occurrence. Because of associated symptoms, this patient was at first thought to be suffering from a nephrotic syndrome. PMID- 1603384 TI - A complicated case of exertional heat stroke in a military setting with persistent elevation of creatine phosphokinase. AB - A case is presented of exertional heat stroke in a military setting with numerous complications that have been previously described. In addition, the complication of late rhabdomyolysis with profound elevation of creatine phosphokinase (CPK) is here described for the first time. This rare condition responded to systemic steroids on this occasion. Late elevation of CPK is a rare complication of exertional heat stroke that appears to respond to systemic steroids. PMID- 1603385 TI - Treatment of gas mask phobia. AB - Many soldiers develop feelings of claustrophobia when wearing a protective mask. In the battlefield environment of today, it is essential that soldiers be able to tolerate gas masks. This article briefly reviews the historical use of gas masks in the U.S. Army. Two cases of treatment of gas mask phobia are described. Behavioral therapy techniques useful for treatment are summarized. PMID- 1603386 TI - Effects of varying doses of smokeless tobacco at rest and during brief, high intensity exercise. AB - To determine the influence of varying doses of smokeless tobacco (moist snuff) on resting heart rate and blood pressure and the performance of brief, high intensity exercise, 12 snuff users were examined at rest and while performing Wingate Anaerobic Tests after taking six different doses of snuff. Snuff caused an increase in heart rate; the larger the dose, the larger the response. Increases in systolic and diastolic blood pressure also occurred but were similar at all doses. Performance of brief, high-intensity exercise was unaffected, so that there was no benefit for such activities (e.g., sprinting bases in base ball). PMID- 1603387 TI - Norfloxacin compared to trimethoprim/sulfamethoxazole for the treatment of travelers' diarrhea among U.S. military personnel deployed to South America and West Africa. AB - A randomized treatment trial of travelers' diarrhea was carried out among U.S. military personnel participating in routine exercises in several port cities in South America and West Africa. A 5-day, twice daily course of either norfloxacin (400 mg) or trimethoprim/sulfamethoxazole (TMP/SMX, 160/800 mg) was given to 142 volunteers. At the end of 5 days of treatment, diarrhea had resolved in 100% of 73 patients receiving norfloxacin and 97.1% (67/69) receiving TMP/SMX. A probable bacterial pathogen was determined in 44% of 142 subjects: 49% of the norfloxacin group and 39% of the TMP/SMX group. The most common pathogens detected were enterotoxigenic Escherichia coli in 20% of cases and rotavirus in 15%. Resistance to TMP/SMX was present in 20 (27%) bacterial isolates, while no resistance to norfloxacin was found. Eight of 10 patients in the TMP/SMX treatment group who had TMP/SMX-resistant bacterial enteropathogens improved clinically. Both norfloxacin and TMP/SMX were clinically effective in the treatment of travelers' diarrhea in this military population. PMID- 1603388 TI - Injuries associated with strenuous road marching. AB - Injuries were recorded during and up to 12 days after a maximal effort road march. Light infantry soldiers (N = 335) carried a total load of 46 kg over a 20 km course. Twenty-four percent of the soldiers suffered one or more injuries, resulting in 44 days of limited duty. All injuries involved the lower extremities and/or the back. Foot blisters and back problems were the most common complaints (35% and 23%, respectively, of the total injuries). These data indicate that units without recent road marching training can expect a high incidence of injuries as a result of a single demanding road march. PMID- 1603389 TI - An evaluation of the impact of "helicopter ride therapy" for in-patient Vietnam veterans with war-related PTSD. AB - An evaluation study is reported about an unprecedented in vivo activity: Huey helicopter rides in the inpatient treatment of post-traumatic stress disorder among Vietnam veterans. A pre- and post-ride attitude survey (N = 45) and clinical observations revealed a series of salient outcomes, including the provocation of pre-existing traumatic memories and pre-flight concerns, profound in-flight reactions, post-flight triggering of intrusive, painful memories, the enhancement of peer group bonding and remembrance of positive war associations, and the desensitization to helicopters and other military stimuli. Theoretical and clinical implications are elaborated. PMID- 1603390 TI - The Special Forces medic: unique training for a unique mission. AB - The U.S. Army Special Forces Medic, Military Occupational Specialty 18D, is a unique, enlisted, medical asset. The training of the 18D is demanding, lengthy, and selective. The 18D is trained to independently assess, and provide acute and long-term medical care for, a variety of medical conditions in support of the Special Forces mission. This article briefly discusses the general missions of U.S. Army Special Operations and Special Forces. This is followed by an in-depth discussion of the 55-week selection and training program of the 18D. PMID- 1603391 TI - Family separations in the military. AB - Family separations are an intrinsic part of military life. The temporary loss of a family member through deployment brings unique stresses to a family in three different stages: predeployment, survival, and reunion. Most families adapt to these stresses well. In families without adequate coping skills, however, these stresses can lead to problems which the family presents to the health care system. Health care providers must be aware of these stresses, the high-risk families, their clinical manifestations, and techniques for preventing and treating them. This article provides some help for health care providers dealing with these issues. PMID- 1603392 TI - A brief review of the epidemiology of HIV in the U.S. Army. AB - The Department of Defense has conducted extensive HIV testing for over 5 years. We summarize the epidemiology of the HIV infection in the total Army. While screening of civilian applicants effectively ensures seronegativity of enlistees, there are approximately 220 new HIV infections each year among active duty soldiers. High-risk demographic groups in the Army include single soldiers, males, those age 25-35, blacks, and Hispanics (including black and Hispanic females). While preventive efforts in the Army should reflect the higher risk experienced by these groups, all soldiers should be made aware of their susceptibility as the epidemic evolves to include more women and heterosexual men. PMID- 1603393 TI - Interventions with medical and psychiatric evacuees and their families: from Vietnam through the Gulf War. AB - Clinical, milieu, and patient management psycho-social interventions are identified and discussed concerning medical and psychiatric evacuees from a war zone. The acute psychological state of evacuees, specific areas of inquiry from the onset of becoming a casualty through initial hospitalization stateside, and interventions to address psychological aspects of being wounded or a psychiatric evacuee are highlighted. Issues and dynamics to address with the families, to include clinical experiences with families of Vietnam, Panama, and Gulf War military returnees are described, as well as specific risk factors for Operation Desert Storm families and personnel. Distinctive stressors faced by women, national guard and reserves, and ethnic minority personnel in Operation Desert Storm are identified. Finally, complications and recommendations concerning the appropriate diagnoses for psychiatric evacuees, and the stressors faced by the health care provider, are presented. Specific recommendations by veterans who themselves were evacuated from Vietnam are described in the veterans' own words. PMID- 1603394 TI - Meckel's stone ileus. AB - Meckel's diverticulum is the most common congenital abnormality of the small bowel; it occurs in approximately 2% of the population. Complications of Meckel's diverticulum include hemorrhage, usually associated with heterotopic tissue within the diverticulum, intussusception, development of benign or malignant neoplasms, and inflammation. Formation of one or more enteroliths within a diverticulum is rare. An extremely rare complication is mechanical small bowel obstruction secondary to extrusion of an enterolith from a Meckel's diverticulum (Meckel's stone ileus). A case of Meckel's stone ileus is described herein, with a review of the literature of this extremely rare complication. PMID- 1603395 TI - Epidemiological characteristics of U.S. fatalities during Desert Storm. PMID- 1603396 TI - A mobile acute trauma battalion aid station: practical application during the Persian Gulf War. PMID- 1603397 TI - Bone healing by induction: clinical perspectives. AB - Treatment of osseous defects by induced bone regeneration has yielded promising results in laboratory animals and in preliminary human trials. Two inducing agents, demineralized bone powder and bone morphogenetic protein, are being used clinically to treat some bony defects without the need for an autogenous bone harvesting procedure. Such off-the-shelf bone-inducing agents may someday become a significant addition to the armamentarium of the military orthopedic surgeon for dealing with the numerous skeletal injuries which occur in today's service environment. PMID- 1603398 TI - Simulator sickness in the U.S. Army UH-60A Blackhawk flight simulator. AB - Realistic training in aviation now includes the use of sophisticated flight simulators which can provide near total perception of aircraft flight. Reports of simulator sickness seem to be increasing in simulators with multi-directional motion, computer-generated imagery, and infinity optics. A voluntary, subjective, symptom-oriented questionnaire was completed by 141 pilots after training in the UH-60A 2B38 Blackhawk flight simulator. Thirty-six percent reported positive symptoms of motion sickness. Pilots may be at risk if they fly too soon after simulator training and a mandatory grounding time is advised. PMID- 1603399 TI - Effect of povidone-iodine irrigation on the preoperative chemical preparation of the eye. AB - Preoperative eyes which had been treated with gentamicin for one-half day were subjected to one of two povidone-iodine (PI) preparations. The control eye was prepared using a previously described 5% PI one-drop technique, while the paired eye was irrigated with a 0.02% PI solution. Aerobic and anaerobic bacterial cultures were taken of each eye before and after PI applications. Statistical analysis of the data indicates that both techniques were equally effective in reducing surface colonization of the anaerobic cocci and bacilli, the viridans streptococci and micrococci. Both methods were also equally ineffective in reducing the numbers of coagulase-negative staphylococci from the surface of the eye. With the apparent emergence of gentamicin-resistant coagulase-negative staphylococci the potential for staphylococcal endophthalmitis is increasing. PMID- 1603400 TI - World War II military led the way in screening chest radiography. AB - World War I recruits were screened for tuberculosis almost exclusively with a history and physical exam. Radiography was unavailable on a large scale and expensive. New techniques developed in Brazil and elsewhere in the 1930s made mass radiographic screening practical. During World War II, the U.S. Army and Navy took advantage of this new technology to screen an estimated 10 million personnel. This ambitious and successful case-finding program inspired, in part, continuing radiographic screening efforts among the civilian population following the war, including mass screening of asymptomatic individuals and routine hospital admission chest films. PMID- 1603401 TI - A study of organizational commitment and job satisfaction among Air Force occupational therapy officers. AB - The purpose of this study is to describe the levels of organizational commitment and job satisfaction found in Air Force occupational therapy officers assigned to the Biomedical Sciences Corps. A questionnaire was mailed to 27 eligible active duty Air Force occupational therapy officers. Of the 23 surveys returned, 22 were usable, an 82% response rate. The occupational therapy officer's demographic characteristics are detailed for all officers and then by company and field grade respondents. Results indicate that these officers have moderately high levels of organizational commitment and job satisfaction. Analyses of the results suggest that field grade officers express more organizational commitment than company grade officers. Both company grade and field grade officers display the same level of job satisfaction. Upon closer scrutiny, though, company grade officers are found to be more satisfied with promotions and rewards gained from their jobs. Field grade officers express higher levels of satisfaction with pay, supervision, and relationship with coworkers. PMID- 1603402 TI - Effect of an experimental antiplaque preparation on salivary microbial counts in military academy cadets refraining from mechanical cleaning of the teeth. AB - Dental emergencies in the army are mostly due to infections of the teeth, caused by dental plaque micro-organisms. Because practicing normal oral hygiene is restricted during terrain maneuvers, for example, we developed a new antiseptic tablet preparation which can be used to make an antiplaque solution or even chewed and thus mixed with saliva to rinse the mouth. The preparation contains chlorhexidine, fluoride, and xylitol (XYLIHEX) and can be added to the soldier's kit. The efficiency of the preparation on selected oral micro-organisms was tested against mouthwash solutions containing plain chlorhexidine (CHX) and sodium fluoride (F) in 45 military cadets who volunteered to participate in this double-blind cross-over study. The results showed a significant decrease in salivary mutants streptococci after rinsing periods with XYLIHEX and CHX when compared with F (p less than 0.001). Lactobacilli and yeast counts were not affected. The new preparation appeared promising as a new means for improving soldiers' oral hygiene. PMID- 1603403 TI - Analyses of battle casualties by weapon type aboard U.S. Navy warships. AB - The number of casualties was determined for 513 incidents involving U.S. Navy warships sunk or damaged during World War II. Ship type and weapon were significant factors in determining the numbers of wounded and killed. Multiple weapon attacks and kamikazes yielded more wounded in action than other weapon types. Multiple weapons and torpedos resulted in a higher incidence of killed in action than other weapons. Penetrating wounds and burns were the most prominent injury types. Kamikaze attacks yielded significantly more burns than incidents involving bombs, gunfire, torpedos, mines, and multiple weapons. Mine explosions were responsible for more strains, sprains, and dislocations than the other weapon types. PMID- 1603404 TI - Therapies for radiation injuries: research perspectives. AB - Exposure to radiation damages the immune, hematopoietic, and gastrointestinal components of the host defense system. This may lead to serious endogenous or exogenous infections. When radiation injury is combined with other physical trauma, e.g., burn or wound, the resulting damage to these systems is synergistic, and treatment for infection requires multiple approaches. This paper reviews successful single and combined therapeutic modalities for infections in irradiated mice and irradiated mice inflicted with trauma that are currently conducted at the Armed Forces Radiobiology Research Institute. The models of endogenous and exogenous infection and combined injury are described. The management of wounds infected with bacteria, exogenous systemic infection due to gram-negative enteric bacteria, and the chemoprophylaxis of enteric-derived systemic infection with quinolones is described. Infections can be treated successfully with proper antimicrobial therapy. In gamma- and neutron-irradiated mice, the immunomodulator trehalose dimycolate (TDM) was effective in treating endogenous infection. TDM with the antimicrobial ceftriaxone was effective in treating exogenous infection due to Klebsiella pneumoniae. Improvement in managing infection in irradiated and injured hosts will require further research using these diagnostic and therapeutic modalities. Accurate biological dosimetry is critical in determining if victims are at risk of developing infection. We found that radiation induced changes in plasma diamine oxidase activity; monitoring these changes was a useful indicator of the severity of radiation injury. PMID- 1603405 TI - Role of the independent duty corpsman on the USNS Comfort (T-AH 20): the Operation Desert Shield/Desert Storm experience. AB - Independent duty corpsmen (IDCs) have a significant role in providing health care on the USNS Comfort (T-AH 20). The IDCs are responsible for staffing sick call, emergency response teams, and resuscitation/stabilization teams. IDCs are trained in advanced patient care and in medical administrative and logistical duties. During peacetime, their function often focuses on primary care to the decrement of skills necessary to perform in medical emergencies. The Operation Desert Shield/Desert Storm mobilization has emphasized the need for Navy medicine to continue its support of IDC training so that they are kept in a state of preparedness to competently deliver the full spectrum of care that is expected of them. PMID- 1603406 TI - Prediction of suicide in military medical facilities. AB - The scope of the suicide problem is briefly reviewed and the distinction between actuarial and clinical prediction is discussed. Three approaches to the process of clinical prediction are (1) use of multiple predictors; (2) use of objective rating scales, and (3) psychodynamic formulation of risk. These are discussed and specific suggestions are offered for incremental implementation in military medical facilities depending on availability of psychiatric resources. The major warning signs of suicidal behavior are outlined and recommendations offered for training of ward personnel. PMID- 1603407 TI - The mandibular third molar position as a predictive criteria for risk for pericoronitis: a retrospective study. AB - During the 6-month period from mid February 1988 to mid August 1988, 148 patients presented with 154 diagnosed cases of mandibular third molar pericoronitis. All patients were members of the recruit population stationed at the Recruit Training Command, Great Lakes, Illinois. Selected clinical parameters relating to the orientation and eruption status of these third molars were collected and analyzed. The goal was to obtain a predictive clinical profile of the impacted mandibular third molar (MTM) at greatest risk for pericoronitis in the young naval and Marine Corps personnel. The majority of pericoronitis cases, 120 of 148 or 81.0%, involved vertically oriented MTMs; of this total, 79.1% were erupted to the approximate height of the occlusal plane of the arch. The remaining 20.9% were at or below the height of contour of the adjacent tooth. Mesioangular impacted MTMs accounted for only 11.2% of pericoronitis cases. The remaining cases comprised distoangular and horizontally impacted MTMs (3.4% and 3.8%, respectively). Involvement by impinging maxillary dentition was observed in 39.7% of the vertically oriented MTMs, 56.2% of the mesioangular oriented MTMs, 40.0% of the distoangular MTMs, and 14.0% of the horizontally impacted MTMs. The mean value for occlusal coverage by a soft tissue operculum observed for all MTMs in this study was 49%. In the population studied, risk for pericoronitis appears to increase with greater vertical orientation and height of eruption. The absence of impinging maxillary dentition did not eliminate the risk of mandibular third molar pericoronitis. These data have implications for targeting treatment needs of naval and Marine Corps personnel who may be without dental support for extended periods of time. PMID- 1603408 TI - A method for shipboard treatment of multiple heat casualties. AB - A method is presented for the treatment aboard ship of multiple patients afflicted with life-threatening heat illness, using an inflatable life raft cooling system. The potential benefits of this method include: (1) the utilization of readily available materials aboard U.S. Naval vessels; (2) the provision for rapid patient cooling by evaporation while maintaining patient safety and comfort; (3) the ability to treat many patients simultaneously with minimal attendant personnel; and (4) the maintenance of patient access allowing for monitoring and the administration of additional supportive measures. PMID- 1603409 TI - The feasibility of an ambulatory surgery service for military personnel. AB - In the past, ambulatory surgery has been considered unsuitable for military personnel. In this pilot study, 69 members of the Israel Defense Forces underwent a variety of surgical procedures on an ambulatory basis in a central, university affiliated general hospital. The waiting time for surgery was considerably reduced. The patients, the army, and the hospital staff were satisfied with the service. Although further study is needed, ambulatory surgery appears to be a suitable and advantageous modality for military personnel. PMID- 1603410 TI - After the Storm: medical officer recruiting and retention. AB - During Operation Desert Shield/Storm, it was necessary to activate and deploy a large number of U.S. Army Reserve and National Guard medical units to augment the active Army health care treatment capability. In addition, a significant number of active Army physicians, nurses, dentists, and other health care providers were ordered from their stateside and European installations to fill positions in field medical units deploying to Southwest Asia. Individual reservists, both from Troop Program Units and from other Selected Reserve programs, were used to backfill active officers and to augment units other than those to which they were normally assigned. The subject of the most often asked questions following the successful conclusion of the war concerns the effect this conflict had on recruitment of health care professionals for the active and reserve forces. This article, while written before many of the medical units returned to their home stations, and while a large number of reservists remain on active duty, will provide an analysis of the war's impact on recruiting in the medical field and identify some incentives that may be needed to ensure the Army Medical Department's capability to meet its mission. PMID- 1603411 TI - Exertional compartment syndrome in a Marine grunt. AB - Exercise-induced exertional compartment syndrome was first described by Vogt in 1945 as "march gangrene." The authors report a case of a 20-year-old United States Marine presenting with the florid findings of acute crural compartment syndrome. The patient's history of prior episodes of crural pain following long hikes led the authors to conclude that this patient had a chronic exertional compartment syndrome. PMID- 1603412 TI - Reflections of a reservist on medical care delivery in an active duty installation. PMID- 1603413 TI - [Aneurysms of the abdominal aorta. Technical aspects]. PMID- 1603414 TI - [Inflammatory aneurysms of the aorta]. PMID- 1603415 TI - [New trends in the surgical treatment of dissecting aneurysm of the ascending aorta]. PMID- 1603416 TI - [Risk factors in gallbladder carcinoma]. PMID- 1603417 TI - [Epidemiology and clinical aspects of gallbladder cancer]. PMID- 1603418 TI - [Diagnosis of gallbladder carcinoma]. PMID- 1603419 TI - [Staging of gallbladder carcinoma in therapeutic management]. PMID- 1603420 TI - [Cancer of the rectum: preoperative staging with endorectal ETG]. PMID- 1603421 TI - [Principles of radical surgery in rectal cancer: the problem of local recurrence]. PMID- 1603422 TI - [Possible use of octreotide in gastrointestinal pathology and in diabetes mellitus]. PMID- 1603424 TI - [Suture materials in microsurgery]. PMID- 1603423 TI - [Complications and results of surgical therapy in Crohn disease]. PMID- 1603425 TI - [Morphofunctional analysis of mucins and endocrine cells in the gallbladder epithelium in uncomplicated cholelithiasis]. PMID- 1603426 TI - [Carcinoma of the thyroid gland with biphasic clinical course and evolution into medullary carcinoma, follicular variant. A case report and immunocytochemical demonstration of the simultaneous presence of calcitonin and thyroglobulin in neoplastic cells]. PMID- 1603427 TI - [An unusual case of ureteral obstruction after kidney transplantation]. PMID- 1603428 TI - [Bladder diverticulosis appearing after kidney transplantation]. PMID- 1603429 TI - [Spigelian hernia: a rare or unrecognized disease?]. PMID- 1603430 TI - [Intraoperative ultrasonography in primary hepatic lesions and metastasis of colonic carcinoma]. PMID- 1603432 TI - [Reoperation in malfunctioning of valve bioprostheses: surgical technique]. PMID- 1603431 TI - [Heart transplantation: the role of histocompatibility]. PMID- 1603433 TI - Gonadotropin-releasing hormone agonist in a GIFT program. AB - The authors describe their experience with the gamete intrafallopian transfer (GIFT) procedure in the treatment of infertility. Utilization of a gonadotropin releasing hormone agonist resulted in a 51.9 percent clinical pregnancy rate and a low cancellation rate. PMID- 1603434 TI - Small fenestra stapedotomy: technique and results. AB - Small fenestra stapedotomy can improve hearing, improve speech discrimination, and reduce the associated risks of conventional stapedectomy. The authors discuss the advantages and disadvantages of small fenestra, as well as the results of their own stapedotomies. PMID- 1603435 TI - Eosinophilia-myalgia syndrome not associated with L-tryptophan. AB - The author reports a case of eosinophilia-myalgia syndrome (EMS), not associated with the use of tryptophan. Other nutritional supplements should be considered as possible etiologic agents in EMS. Further research in this area is needed. PMID- 1603436 TI - Results of surgery and radiotherapy for early breast cancer. AB - Primary radiotherapy for 127 early breast cancers produced five-year local control of 96.1 percent and NED results of 81.1 percent. Results from a large community cancer center in New Jersey are comparable to results of major university cancer centers. PMID- 1603437 TI - New Jersey's 15-year experiment in altered physician-patient relations. AB - New Jersey has served as a "social laboratory" by initiating innovations affecting physician-patient relations. Some of these changes include use of ethics committees, influence of the Bioethics Commission, and government review of nursing home decision making. PMID- 1603438 TI - Compliance with new OSHA bloodborne standard. AB - New Jersey physicians who have office staff giving injections, performing venipuncture, analyzing body fluids, or assisting with minor surgical procedures must comply with OSHA's bloodborne Standard. The Standard became effective on March 6, 1992. PMID- 1603439 TI - Endoscopic diagnosis of anorectal melanoma. AB - Symptoms of anorectal melanoma commonly are attributed to hemorrhoids. The authors believe recognition of the sigmoidoscopic appearance will allow the physician to distinguish this condition from the more common anorectal disorders. PMID- 1603440 TI - Depression may be overlooked as a progesterone side effect. PMID- 1603441 TI - The epidemiology, clinical manifestations and health-maintenance needs of women infected with HIV. AB - The growing epidemic of HIV infection poses a serious threat to women's health in the United States and abroad. In the United States, HIV disproportionately affects African-American and Hispanic-American woman. Primary care providers will be faced with an increasing need to provide counseling and clinical services to these women. It is not yet clear whether gender affects the natural history of HIV infection; differences in survival rates may reflect lack of access to care rather than true biologic differences. Opportunistic infections among women with HIV infection are similar to those found among men with AIDS who use injection drugs. Unique expressions of HIV disease associated with women's reproductive tracts include persistent vaginal candidiasis, human papillomavirus infections and cervical dysplasia. Women with HIV infection should receive thorough gynecologic screening, including Pap smears, every six months. Women who know they are HIV positive may choose to become pregnant; these clients require extensive prenatal care and state-of-the-art HIV management. PMID- 1603442 TI - Congenital hip dislocation: the importance of early detection and comprehensive treatment. AB - Hip dislocation is the musculoskeletal condition most commonly missed during neonatal examinations. Failure to diagnose the condition can lead to long-term disability and is a common target in pediatric legal suits concerning damage to the musculoskeletal system. Early neonatal assessment for hip dislocation includes an examination using the Barlow and Ortolani tests. Later examinations include assessment of gluteal folds, knee height and the degree of hip abduction. The preferred treatment is use of the Pavlik harness, an outpatient treatment regime that provides effective reduction in 90 percent of the cases. The harness uses flexion and free abduction to direct the femoral head into the acetabulum; it uses time, gravity and motion to position the hip in a reduced position. The harness requires three to six months of continuous wear for the hip to become radiographically stable. Health care providers are instrumental in diagnosing congenital hip dislocation and teaching families how to promote the infant's physical and psychosocial well-being. If this condition is not detected until after the infant is 6 weeks old, or the harness is ineffective after three weeks, skin traction, closed reduction and spica-cast application may be needed. Open reduction and recasting are also options. In rare cases, total hip replacement is necessary in later life. PMID- 1603443 TI - Effective treatment of Chlamydia trachomatis infection during pregnancy to prevent perinatal and infant complications. AB - Chlamydia trachomatis is the most prevalent cause of sexually transmitted disease in the United States today. Prenatal health care providers must learn to recognize and effectively treat chlamydial infection in order to help prevent serious consequences in the pregnant woman and in the neonate. This article discusses the diagnosis and treatment of chlamydial infection during pregnancy and during the neonatal period. Patient education of women infected during pregnancy should include guidelines for helping parents and care providers monitor the neonate for signs of conjunctivitis and pneumonia. PMID- 1603444 TI - Restructuring the American health care system: an analysis of Nursing's Agenda for Health Care Reform. AB - Equal access to health care for all citizens is a hotly debated issue of the American health care system. Different plans for reform that would allow equal access to health care have been proposed, but few include nurses as key health care providers. To correct this oversight, a coalition of more than 60 national nursing and health care organizations has created Nursing's Agenda for Health Care Reform, a blueprint for restructuring the health care system. This article reviews the agenda within the framework of the ethical theory of distributive justice. Distributive justice allows for the allocation of health care resources in a manner that is fair but not necessarily equal for all. The agenda addresses the basic level of health care needed by all Americans and supports the provision of primary care by nurse practitioners. Nurse practitioners need to be aware of plans to reform the health care system and should be supportive of those plans that enhance nurse participation in the health care system. Nursing's Agenda for Health Care Reform is a plan that encourages the health care consumer's participation and promotes nursing care as the link between the consumer and the health care system. PMID- 1603445 TI - Acyclovir approved for childhood chickenpox. PMID- 1603446 TI - Cefixime offers effective oral therapy for gonorrhea. PMID- 1603447 TI - Cimetidine and ranitidine affect blood-alcohol levels. PMID- 1603449 TI - A new threat to public health: organochlorines and food. AB - Ambient levels of persistent toxic chemicals, chemicals that persist for decades in the environment, have reached levels high enough to affect the health of children. The organochlorines (PCBs, DDT and the dioxin family) accumulate in human adipose tissue. Pregnant women pass the contamination to their fetuses. The developing nervous system is the most vulnerable. Neurobehavioral deficits, including short-term memory loss, are detected in children born to mothers at the high end of the distribution curve of organochlorines. Humans are not alone in their susceptibility to these subtle effects. Wildlife exposed to the same spectrum of organochlorines as humans suffer a variety of behavioral changes. Rats and Rhesus monkeys fed diets containing the organochlorines under laboratory conditions exhibit behavioral changes that persist into adulthood. For humans, food provides 80 percent of organochlorine contamination. Meat, fish, dairy and commercial fruit are the main sources. A vegetarian diet including unsprayed fruit minimizes contamination. The ultimate solution to this public health problem is elimination of the organochlorines from the environment. PMID- 1603448 TI - Incorporating explanatory models in planning nutrition education programmes in Thailand. AB - An intersectoral child development services project is being undertaken in Thailand to develop a model process for providing age appropriate care and education to rural children through an integrated programme of nutrition, health and educational services designed to meet community needs and perceptions. Using behavioral analysis and explanatory models, project results show that the effectiveness of nutrition education can be facilitated by (1) recognizing the family as the unit of service, (2) focusing on solutions rather than problems, (3) using a two-stage promotional message strategy to encourage better child caretaking, and (4) viewing potential new practices as behavioral processes, rather than single entities aimed at a specific outcome. Program planning should also include the successive construction and analysis of community-based explanatory models which justify people's nutrition and health behaviors. The ultimate aim is to identify differences between explanatory models held by community members and health/nutrition educators, negotiate this conflict, and thereafter develop more practical and realistic methods for modifying behavior. PMID- 1603450 TI - Dialysis liability. PMID- 1603451 TI - Nursing kaleidoscope: clinicians as teachers. PMID- 1603452 TI - The issue of reimbursement. PMID- 1603453 TI - Technology and advanced nursing practice. PMID- 1603454 TI - Mergers: from three nursing departments to one nursing system. PMID- 1603455 TI - Merging two nursing units: no time for turmoil. PMID- 1603456 TI - Hospital merger: three weeks to M-day. PMID- 1603457 TI - Mergers: from two obstetrical departments to one. PMID- 1603458 TI - Product evaluation: air-fluidized beds in an operational setting. PMID- 1603459 TI - Role competencies of first-line managers. PMID- 1603460 TI - How much are nurses worth? Nurses evaluate themselves. PMID- 1603461 TI - Lifelong learning: putting reading first. PMID- 1603462 TI - Advancing staff education. PMID- 1603463 TI - Improving nursing satisfaction. PMID- 1603464 TI - Technology assessment: the road to appropriate equipment & care. PMID- 1603465 TI - Redesigning work: the cardiac intervention nurse liaison. PMID- 1603466 TI - Career scope--Northeast. PMID- 1603467 TI - For sale to the highest bidder? PMID- 1603468 TI - Ventilation perfusion imaging--again. PMID- 1603469 TI - User requirements for information systems in nuclear medicine. AB - In the field of COST cooperation (COST = European Cooperation in the Field of Scientific and Technical Research) a project B2 for Quality Assurance in Nuclear Medicine Software has been established. In a memorandum of understanding setting up this project, user requirements were to be defined for the hardware and software used for data acquisition, processing and presentation. A subgroup of the management committee of COST B2 were interested in the Advanced Informatics in Medicine, AIM, task T-734 'Quality Assurance of Medical Software', and the AIM Project 'A 1034', coordinated by Dr K. Britton, was initiated. The initial drafts of this document were written in Helsinki during 1988-1990, and submitted for comment by the members of the management committee of COST B2. These comments were integrated in the text and this document was finalized by the UK group so as to make it available for international discussion. It is anticipated that, after appropriate international discussion, these User Requirements for Information Systems in Nuclear Medicine will be adopted by the management committee of COST B2 as a COST document. Towards these ends, a working group chaired by Dr Britton, including the British and Finnish teams and Ulrich Noelpp from Switzerland, was appointed by the management committee of COST B2 in April 1990. While writing it we have had the pleasure of working with referees from different European hospitals in many countries. We are happy to thank all of them for their valuable contributions. PMID- 1603470 TI - Spontaneous variability of left ventricular ejection fraction assessed with the Cardioscint. AB - A miniature, non-imaging caesium iodide nuclear probe optically coupled to a photodiode (the 'Cardioscint') has been developed which, in conjunction with a modified personal computer, is capable of continuous on-line monitoring of left ventricular function and ST-segment level at the bedside. The purpose of this study was to assess the variability in ejection fraction over periods of time and to compare this variability with that of equilibrium gamma camera radionuclide ventriculography. Ten normal volunteers (nine male) of mean (S.D.) age 49 (10) years underwent semisupine radionuclide ventriculography using both gamma camera and Cardioscint in randomized order. The gamma camera recorded four consecutive acquisitions (mean of 7.2 min each) and the Cardioscint, using a 20 s acquisition time, recorded left ventricular function over 35 min per subject. The mean ejection fraction of the group by gamma camera was 52 (7)% and by Cardioscint was 54 (5)%. When the variability in ejection fraction by gamma camera was compared with the Cardioscint averaged over corresponding time periods (i.e. an average of 7.2 min), the mean coefficient of variation of the camera was 5.0% versus 2.9% for the probe system. Individual 20-s probe acquisitions over the total study duration (reflecting the short-term variability of the system) had a coefficient of variation of 5.1%. Thus the Cardioscint provides a stable continuous recording of ejection fraction. These volunteer data provide a basis for interpretation of data acquired in the clinical situation. PMID- 1603471 TI - 153Sm-EDTMP and melphalan chemoradiotherapy regimen for bone marrow ablation prior to marrow transplantation: an experimental model in the rat. AB - Chemoradiotherapy with melphalan and 153Sm-ethylenediaminetetramethylene phosphonate (EDTMP) was used to ablate bone marrow in WAG rats which were subsequently rescued by marrow transplantation. Internal irradiation of bone marrow with high doses of up to 3.5 GBq kg-1 153Sm-EDTMP alone produced profound, but self-limiting, myelosuppression and all animals recovered spontaneously. Melphalan alone in doses of 9.5 mg kg-1 also caused transient myelosuppression without mortality. However, the combination of 9.5 mg kg-1 melphalan and 555 MBq kg-1 153Sm-EDTMP caused marrow ablation and death in 80% of animals. The mortality of this chemoradiotherapy regimen was reduced to 7% by sequential administration of 153Sm-EDTMP on day 0 and melphalan on day 5 followed by marrow transfusion of 7.5 x 10(7) cells on day 6. These results were comparable to those obtained following bone marrow transplantation 24 h after lethal total body external beam irradiation. In the inbred WAG rat experimental model the sequential chemoradiotherapeutic regimen of internal irradiation with 153Sm-EDTMP followed by chemotherapy with melphalan was demonstrated to ablate bone marrow effectively whilst preserving the capacity for recovery following marrow transplantation. PMID- 1603472 TI - 99Tcm-labelled IgG scanning does not predict the distribution of intestinal inflammation in patients with inflammatory bowel disease. AB - In order to assess the value of 99Tcm-labelled-immunoglobulin G(99Tcm-IgG) in the assessment of the activity and distribution of intestinal inflammation in patients with inflammatory bowel disease (IBD), 99Tcm-IgG scans were performed in 18 patients. Patients were divided clinically into two groups, those with (ten patients) and those without (eight patients), intestinal inflammation. Disease activity and distribution were assessed by 111In-oxine granulocyte scanning and/or histological extent of inflammation at endoscopy or surgery in all patients with IBD and most of those without intestinal inflammation. In the assessment of the presence or absence of inflammation, a sensitivity of 80% and specificity of 87% were achieved. However, when the localization of intestinal inflammation was evaluated, only five of eight true positive scans were concordant with the distribution of intestinal inflammation as determined by other methods. Thus, significant areas of inflammation were missed in five of ten patients with IBD (two false negative, three incorrect localization of inflammation). Although 99Tcm-IgG scanning appears to have moderate sensitivity and acceptable specificity in the detection of intestinal inflammation, it performs poorly in assessing the distribution of inflammation and is, therefore, of little value in the assessment of patients with suspected or proven IBD. PMID- 1603473 TI - Analysis of immunoradiological properties of radiolabelled monoclonal antibody for tumour localization. AB - This investigation demonstrates the effect of 131I incorporation on antibody function and radionuclide delivery to target antigens by radiolabelled antibody. For our antihepatoma monoclonal antibody with affinity constant K = 1.12 x 10(8) M-1 and maximum binding capacity of 1.66 x 10(6) sites on each hepatoma cell, a linear decrease in K was observed with the increase in specific activity from 1.90 to 97.12 microCi microgram-1. Radioiodination also inactivated nearly half of the immunoreactive molecules. Most interestingly, when magnitudes of antibody mass and radioactivity which bound target cells were compared for preparations of different specific activities, each contained similar nanomolar of antibody molecules. We recognized the slight gain in nanogram bound opposing to the great loss in bound counts per minute (cpm) as consequences of decreasing levels of 131I incorporation from 97.12 and 26.64 to 1.90 microCi microgram-1. Our findings suggest that the quality of radiolabelled antibody should be assessed in both its immunological function and radioactive transfer capability. PMID- 1603474 TI - Transport of 67Ga and 111In across a membrane. Role of plasma binding and concentration gradients. AB - If i.v. injected radiogallium does not firmly bind to circulating transferrin in plasma, the transvascular transport of the radionuclide may be affected by diffusion of unbound radionuclide and interstitial transferrin, and may therefore not be specific for transferrin transport. Using equilibrium dialysis, the avidity of 67Ga and 111In to bind to plasma transferrin was compared by evaluating transport of unbound radionuclide across a semipermeable membrane, as a function of the plasma (transferrin) concentration gradient. One chamber of a dialysis cell was filled with human plasma and 67Ga or 111In, and the other, separated by the membrane, with increasing concentrations of plasma in normal saline. The half-time (mean +/- S.D.) for reaching equilibrium between the chambers decreased (P less than 0.05) for 67Ga from 13.1 +/- 3.3 to 4.9 +/- 1.6, 3.7 +/- 1.2 and 3.0 +/- 0.5 h, at plasma concentrations of 0, 25, 50 and 100%, respectively. The equilibrium half-time for 111In did not fall at increasing plasma concentrations and was higher (P less than 0.005) than for 67Ga at 25 to 100% plasma. Hence, 67Ga is not as avidly bound to plasma transferrin as 111In, since, in contrast to 111In, dissociation of the 67Ga-transferrin complex and transmembrane diffusion of unbound 67Ga increases when the plasma transferrin concentration gradient decreases. In vivo, the transvascular transport of 67Ga may be influenced by diffusion of unbound radionuclide, depending on the interstitial transferrin concentration, and may not be a specific indicator of transvascular protein transport. PMID- 1603475 TI - Altered regional clearance of 99Tcm-DTPA in radiation pneumonitis. AB - 99Tcm-diethylene triaminepenta-acetic acid (99Tcm-DTPA) lung scintigrams were investigated in 11 patients with radiation pneumonitis to assess the alteration of clearance of this small solute. Thirty minutes after the injection of 99Tcm DTPA, all 11 patients showed abnormal accumulation. This uptake was seen in the areas with reduced 99Tcm-macroaggregated albumin activity. The curves of the lung/heart ratios obtained after 1 min after injection of 99Tcm-DTPA in areas showing abnormal accumulation were of three types. Comparison of the slope for the initial 5 min of the lung/heart curves between the abnormal accumulation sites and the contralateral non-irradiated lung revealed a significant difference. The uptake ratio (the mean counts of the last frame divided by initial peak count) was related to the degree of abnormal accumulation in the radiation pneumonitis. Moreover, study of rabbits with radiation pneumonitis revealed similar behaviour by 99Tcm-DTPA as observed clinically. This simple and rapid method may be useful in detecting and monitoring the altered regional kinetics of 99Tcm-DTPA in radiation pneumonitis. PMID- 1603476 TI - Invasive cancer of the cervix in British Columbia: a review of the demography and screening histories of 437 cases seen from 1985-1988. AB - The charts of 437 patients with newly diagnosed invasive cervical cancer seen in British Columbia during 1985-1988 were reviewed to determine the age at diagnosis, stage of disease, and histology of the lesions. The patient's immigration status and country of birth were also examined. Two hundred forty-two patients (55%) were age 50 or over and 149 (34%) had preclinical stage IB disease. One hundred seventy of these patients (39%) had never had a cytologic examination before presenting with clinical symptoms, and 45 additional patients had not had cytology for 5 or more years before presenting with invasive disease; thus, a total of 215 cases (49%) fell into the category of "no cytology or cytology longer than 5 years ago." All negative smears were reviewed and in 39 patients (15%) having previous cytology, abnormal cells had been missed or undercalled. Native Indian women made up 10% of the cases of invasive carcinoma, a disproportionately large number as they represent only 2% of the British Columbian population. Of the 27 Native Indian patients in this series, 16 (59%) had never had a cytologic examination. Eighty-five (30%) of 276 women born in Canada had never had a cytologic examination, compared with 34 (71%) of 48 immigrants resident in the country for fewer than 10 years. Twenty-four patients were over the age of 60 with a history of negative Papanicolaou smears. We conclude that, if further gains are to be made in the reduction of death rates from invasive cervical carcinoma, new means must be found to encourage women to participate in Papanicolaou smear screening programs. In particular, special efforts must be made to attract specific groups, such as the Native Indian population and older recent immigrants. PMID- 1603477 TI - Biophysical profile as a predictor of amniotic fluid culture results. AB - The biophysical profile has been proposed as a noninvasive method of detecting fetal infection in patients with preterm premature rupture of membranes (PROM). The purpose of this study was to evaluate the biophysical profile as a rapid predictor of amniotic fluid (AF) culture results in women with PROM. Amniocentesis was performed on 111 patients with PROM at or before 34 weeks' estimated gestational age. Aerobic, anaerobic, Ureaplasma, and Mycoplasma cultures were performed on the AF. A biophysical profile was performed just before the amniocentesis. Women with positive AF cultures had a significantly lower total biophysical profile score, as well as significantly lower scores for nonstress test, fetal breathing movements, fetal movements, and AF volume, than those with negative AF cultures. However, neither the total biophysical profile score nor any of the individual components had sufficient sensitivity, specificity, or positive or negative predictive value to be useful clinically in predicting culture results. Although the incidence of positive AF cultures was inversely related to the biophysical profile score, 48% of patients with a score of 8 and 27% of those with a score of 10 had positive AF cultures. The results of this study do not support use of the biophysical profile as an early predictor of AF culture results in patients with PROM. PMID- 1603478 TI - The biophysical profile and the nonstress test: poor predictors of chorioamnionitis and fetal infection in prolonged preterm premature rupture of membranes. AB - Sixty-eight women admitted with the diagnosis of preterm premature rupture of membranes (PROM) and a latency period of at least 48 hours were followed expectantly. Fetal surveillance consisted of daily kick counts, daily nonstress test (NST), and fetal biophysical profile every 48-72 hours. Patients were delivered as a result of spontaneous labor, clinical chorioamnionitis, fetal distress, or attainment of 37 weeks' gestation. No corticosteroids, tocolytics, or prophylactic antibiotics were used. The last biophysical profile and the last NST before delivery were evaluated for each patient. There was no statistically significant association between chorioamnionitis or fetal infection and the following: 1) a low biophysical profile (score of 6 or lower), 2) a low biophysical profile that included a nonreactive NST and absent fetal breathing movements, or 3) a nonreactive NST. We conclude that the biophysical profile and the NST are poor predictors of perinatal infectious complications. PMID- 1603479 TI - High- versus low-dose oxytocin for labor stimulation. AB - The number of cesarean births for dystocia has increased dramatically in the United States. Central to the management of dystocia is correction of ineffective labor by oxytocin administration, and contemporary obstetric practice is to stimulate labor with a low-dose oxytocin regimen. We prospectively compared a low dose oxytocin regimen (1-mU/minute dosage increments) with a high-dose regimen (6 mU/minute dosage increments) in 2788 consecutive singleton cephalic pregnancies. The low-dose regimen was used first for 5 months in 1251 pregnancies, and the high-dose regimen in 1537 pregnancies during the subsequent 5 months. Indications for oxytocin stimulation were divided into augmentation (N = 1676) and induction (N = 1112). Labor stimulation was more than 3 hours shorter (P less than .0001) with the high-dose oxytocin regimen and associated with a reduction in neonatal sepsis (0.2 versus 1.3%; P less than .01). Uterine hyperstimulation was more common (55 versus 42%; P less than .0001) with the high-dose regimen, but no adverse fetal effects were observed. High-dose augmentation resulted in significantly fewer forceps deliveries (12 versus 16%; P = .03) and fewer cesareans for dystocia (9 versus 12%; P = .04). Similarly, failed induction was less frequent with high-dose compared with low-dose oxytocin (14 versus 19%; P = .05). Although the high-dose induction regimen was associated with a significantly increased cesarean incidence for fetal distress (6 versus 3%; P = .05), the incidence of umbilical artery cord blood acidemia was not increased in this subset. Induction of labor with high-dose oxytocin is problematic because of risk-benefit considerations. Although induction failed less frequently with the high-dose regimen, cesarean for fetal distress was performed more frequently. In contrast, high-dose oxytocin to augment ineffective spontaneous labor minimized the number of cesareans done for dystocia. PMID- 1603480 TI - Predictors of antibiotic prophylactic failure in post-cesarean endometritis. AB - Despite the use of prophylactic antibiotics, endometritis occurs in 1-31% of patients after cesarean delivery. We sought to identify predictors of prophylactic antibiotic failure. In a retrospective review of 1800 cesarean deliveries, 766 patients had either ampicillin or cefazolin prophylaxis; 240 (31.3%) developed endometritis. Stepwise logistic regression identified the number of vaginal examinations (P less than .001), nulliparity (P = .001), low gestational age (P = .033), and cefazolin use (P = .002) as predictors of endometritis. One in two women with six or more vaginal examinations before cesarean delivery will have prophylactic failure. In preterm gestations (N = 177), the number of vaginal examinations was the single predictor of prophylactic antibiotic failure (P = .002). The number of vaginal examinations can be used to design new strategies to prevent a high rate of prophylactic failure. PMID- 1603481 TI - Life span of erythrocytes in late pregnancy. AB - OBJECTIVE: Based on previous studies that demonstrated lighter and larger erythrocytes in late pregnancy, we hypothesized that the life span of erythrocytes in late pregnancy is shorter than in nonpregnant women. METHODS: We used the density distribution of cells to evaluate the age distribution of erythrocytes in pregnant versus nonpregnant women and rats. The life span of erythrocytes was compared between pregnant rats and nonpregnant syngeneic rats of the same age using 51Cr for labeling erythrocytes. RESULTS: Based on the density distribution of cells, a similar shift to lighter erythrocytes was found comparing pregnant to nonpregnant women and rats. The pregnant rat erythrocytes had a shorter life span by 9.2% (33.6 versus 36.9 days; P = .0010). CONCLUSIONS: The life span of erythrocytes in pregnant rats is shorter than in nonpregnant ones. A similar shift in the age distribution of pregnant rat and pregnant human erythrocytes is probably associated with a similar life span of pregnant rat and pregnant human erythrocytes. The shorter life span of erythrocytes in late pregnancy may be attributed to higher erythropoietin levels in pregnancy, which induce "emergency hematopoiesis" resulting in younger reticulocytes and macrocytic erythrocytes, which are known to have a shorter life span. PMID- 1603482 TI - Recombinant human erythropoietin in the treatment of postpartum anemia. AB - Postpartum maternal anemia (hemoglobin concentration below 10 g/dL) is a common problem in obstetrics. Human recombinant erythropoietin, which has been shown to correct the anemia of end-stage renal disease and eliminate the need for transfusions, was used in a comparative study of women with postpartum hemoglobin concentrations below 10 g/dL. Five daily doses of 4000 IU were given. Hematologic and clinical data were compared on days 5, 14, and 42 after therapy in the treated women and in untreated women. Both groups received the same iron and folic acid supplements. Significantly greater increases in reticulocytes, hemoglobin, and hematocrit were seen by day 5 for the treated subjects compared with controls. Ferritin levels were significantly lower in the therapy group than in controls. No differences were seen between the groups in the platelet counts or clinical characteristics. No negative side effects were observed. As in other studies in populations without renal disease, recombinant human erythropoietin enhanced endogenous erythropoiesis over and above the normal physiologic recovery rate. PMID- 1603483 TI - Hospital hazards. PMID- 1603484 TI - Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. AB - Detection of ovarian cancer at an early stage should reduce the mortality associated with this disease. Through the Stockholm Population Registry, 5550 apparently healthy women were enrolled in a study designed in part to define the use of the CA 125 radioimmunoassay (RIA) as an initial test for early detection of ovarian cancer. Women whose CA 125 levels were elevated and an equal number of age-matched controls with normal levels were followed by means of pelvic examinations, transabdominal sonography, and serial CA 125 determinations. Of the 175 women with high CA 125 levels, six were found to have ovarian cancer: two each in stages IA, IIB, and IIIC. Of those with normal-range CA 125 levels, three had ovarian cancer as identified through the Swedish Cancer Registry; all three were under 50 years of age. Ovarian cancer was diagnosed on laparotomy in six of the women age 50 or over. Using thresholds of 30 and 35 U/mL, the rates of specificity for the CA 125 RIA were 97 and 98.5%, respectively, for women age 50 or older, and 91 and 94.5%, respectively, for those younger than 50 years of age. Thus, the specificity of the CA 125 RIA is adequate in postmenopausal women to undertake a larger study to determine whether screening using CA 125 influences survival of patients with ovarian cancer. PMID- 1603485 TI - Indications, techniques, and advantages of partial laser vaginectomy. AB - Partial vaginectomy is seldom used diagnostically to evaluate vaginal neoplasia because of its technical difficulty, the possible need for grafting, and postoperative vaginal agglutination or stenosis. We found that use of the carbon dioxide laser simplified vaginectomy in ten subjects, producing a low rate of complications, an excellent diagnostic specimen, and superior healing. PMID- 1603486 TI - Outpatient vaginal hysterectomy: a pilot study. AB - To determine the feasibility and safety of outpatient vaginal hysterectomy, we conducted a prospective study of 35 patients. Inclusion criteria required that the patient: 1) had no medical problems requiring hospitalization, 2) had a working telephone and a support person during the first 48 postoperative hours, 3) signed an informed consent document and understood the postoperative instructions, 4) required no concomitant surgical procedure such as anterior or posterior colporrhaphy, 5) required no additional antibiotic therapy for valvular heart disease, and 6) sustained no intraoperative injury requiring hospital monitoring. A physician contacted the patient by telephone on the evening of surgery and on postoperative days 1 and 2, and a nurse saw each patient in her home on postoperative days 1 and 2. Total hospital stay from admission to discharge from the ambulatory surgery unit was 9.4 +/- 0.81 hours (range 7.8 10.6). The mean preoperative hematocrit was 37.0 +/- 3.5% (range 29.3-43.5), with a mean discharge hematocrit of 32.5 +/- 4.2% (range 27-39). Follow-up hematocrit measurements at 24 hours, 48 hours, and 1 week were unchanged (P greater than .05) from that at hospital discharge. Two patients required hospital readmission, one on postoperative day 7 for a vaginal cuff abscess and another on postoperative day 3 for a spinal headache. On a 13-item questionnaire, most subjects rated the entire outpatient experience positively. These data suggest that outpatient vaginal hysterectomy can be a safe procedure and is well-accepted by selected patients. Based on these preliminary findings, an expanded clinical trial is warranted. PMID- 1603488 TI - Differentiating malignant from benign ovarian tumors with transvaginal color flow imaging. PMID- 1603487 TI - Fetal cells in the maternal circulation: detection of Y-sequence by gene amplification. AB - Detection of a Y-specific sequence in the maternal circulation has clinical importance because it would be useful in determining fetal gender in mothers with severe X-linked disorders. The method described in this paper has the advantage of requiring only small amounts of maternal blood. Numerous attempts have been made to identify XY cells in the blood of mothers bearing male fetuses; however, the results have been controversial. In this study, a member of the DYZ1 family and the XY homologous region of the amelogenin gene were used as targets for polymerase chain reaction detection of the Y chromosome. The subjects in this study were a group of 100 pregnant women at 17-20 weeks' gestation and 30 puerperal women who had given birth 2-5 days previously. All of the former underwent amniocentesis, with venous blood samples drawn before the procedure. Forty-five fetuses were confirmed as male by karyotyping amniocytes, and 30 of these were positive for the Y sequence in the DYZ1 region (sensitivity 66.7%). However, ten of the 55 cases diagnosed as female were also positive, giving a specificity of only 81.8%. Thus, the positive and negative predictive values were each 75%. In the amelogenin gene study, a positive Y signal was not detected in any of the cases examined. This study demonstrates the usefulness of polymerase chain reaction detection of Y-specific sequences in the maternal circulation. However, further investigation is necessary to increase the reliability for clinical application, because the method does produce false-positive results. PMID- 1603489 TI - Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. PMID- 1603490 TI - Changing obstetric practice and 2-year outcome of the fetus of birth weight under 1000 g. PMID- 1603491 TI - Perineal exposure to talc and ovarian cancer risk. AB - OBJECTIVE: We sought to determine whether the use of talc in genital hygiene increases the risk for epithelial ovarian cancer. METHODS: We interviewed 235 white women diagnosed with epithelial ovarian cancer between 1984-1987 at ten Boston metropolitan area hospitals and 239 population-based controls of similar race, age, and residence. RESULTS: Overall, 49% of cases and 39% of controls reported exposure to talc, via direct application to the perineum or to undergarments, sanitary napkins, or diaphragms, which yielded a 1.5 odds ratio (OR) for ovarian cancer (95% confidence interval [CI] 1.0-2.1). Among women with perineal exposure to talc, the risk was significantly elevated in the subgroups of women who applied it: 1) directly as a body powder (OR 1.7, 95% CI 1.1-2.7), 2) on a daily basis (OR 1.8, 95% CI 1.1-3.0), and 3) for more than 10 years (OR 1.6, 95% CI 1.0-2.7). The greatest ovarian cancer risk associated with perineal talc use was observed in the subgroup of women estimated to have made more than 10,000 applications during years when they were ovulating and had an intact genital tract (OR 2.8, 95% CI 1.4-5.4); however, this exposure was found in only 14% of the women with ovarian cancer. CONCLUSIONS: These data support the concept that a life-time pattern of perineal talc use may increase the risk for epithelial ovarian cancer but is unlikely to be the etiology for the majority of epithelial ovarian cancers. PMID- 1603492 TI - Peritoneal fluid inhibin during the menstrual cycle. AB - Serum and peritoneal fluid inhibin levels were measured by radioimmunoassay throughout the menstrual cycle in 14 women with endometriosis and in 16 controls. In controls, serum values (+/- standard error of the mean) increased from the early follicular phase (49.8 +/- 6.5 microLEq/mL) to the late follicular phase (178 +/- 37.8 microLEq/mL) and the luteal phase (346 +/- 98.3 microLEq/mL). Peritoneal fluid inhibin levels were several-fold higher than those in serum and reached a maximum value during the late follicular phase (early follicular: 2404 +/- 85 microLEq/mL, late follicular: 22,922 +/- 7145 microLEq/mL, luteal: 5195 +/ 1959 microLEq/mL). There was no difference in peritoneal fluid or serum inhibin concentrations between patients with and without endometriosis. These findings suggest that human gametes in the fallopian tube may be exposed to a very high concentration of inhibin. The lack of difference in inhibin concentrations between patients with and without endometriosis suggests that this hormone does not play a role in endometriosis-related infertility. PMID- 1603493 TI - Estrogen use and depressive symptoms in postmenopausal women. AB - The potential antidepressant effects of estrogen replacement therapy were examined cross-sectionally in a population of 1190 women 50 years and older living in Rancho Bernardo, California. Of the total, 294 (24.7%) were currently using estrogen. Among women aged 50-59 years, those currently using noncontraceptive estrogen had a significantly higher rate of Beck Depression Inventory scores of 13 or higher than all untreated women of the same age and higher mean depressive symptom scores than women who had never used estrogen. However, after age 60, mean depressive symptom scores and rates of categorical depression increased significantly in the untreated women but not in the treated women. A similar pattern was found when depressive symptom measures of treated and untreated women were stratified by the number of years since last menstrual period. Greater depressive symptoms in currently treated versus untreated women aged 50-59 years may reflect treatment selection bias, as a higher proportion of symptomatic depressed climacteric women seek treatment. The decreased risk of depressive symptoms after age 60 may reflect a long-term benefit of estrogen replacement or the selective discontinuation of estrogen by depressed women. In this cohort, reports of hot flushes, moods, and insomnia as the reason for estrogen use fell in parallel with a decline in depressive symptoms with increasing age, suggesting that hormone replacement therapy provided relief of physical symptoms, ie, possible causes of psychological distress. Clinical trials are needed to confirm these observations and postulated explanations. PMID- 1603494 TI - Minimal endometriosis and intrauterine insemination: does controlled ovarian hyperstimulation improve pregnancy rates? AB - Fifty normally menstruating women staged laparoscopically as having minimal endometriosis were given an option to be treated with intrauterine insemination with or without ovarian stimulation. Twenty-five patients had unmedicated natural cycles (ie, no medication for follicular stimulation), and 25 underwent controlled ovarian hyperstimulation. All subjects received hCG to time ovulation, followed 36 hours later with intrauterine insemination. Sixteen pregnancies, eight in each group, resulted from a total of 132 cycles. The cumulative probabilities of conception for the first, second, and third cycles were 0.13, 0.26, and 0.38 in the natural-cycles group and 0.12, 0.25, and 0.34 in the medicated-cycles group, respectively (P greater than .05). Monthly fecundity was 0.14 for the natural-cycles group and 0.13 for the medicated-cycles group (P greater than .05). We conclude that there is no difference in pregnancy rates or monthly fecundity over a 3-month period with controlled ovarian hyperstimulation as opposed to natural cycles combined with intrauterine insemination. PMID- 1603495 TI - Clitoral size in normal women. AB - OBJECTIVE: We sought to determine clitoral size in normal women and the possible effect of age, height, weight, parity, and oral contraceptive (OC) use. METHODS: Prospective measurement was made of clitoral dimensions in 200 consecutive normal women at routine gynecologic examination in an office setting. RESULTS: The mean (+/- standard deviation) transverse diameter of the glans clitoris was 3.4 +/- 1.0 mm. The longitudinal diameter of the glans was 5.1 +/- 1.4 mm. Total clitoral length including glans and body was 16.0 +/- 4.3 mm. The mean clitoral index was 18.5 mm2. Measurements of all diameters were normally distributed. Age, height, weight, or current use of OCs did not influence clitoral size, but parous women had significantly larger measurements. CONCLUSIONS: It is possible to obtain useful clitoral measurements in the office setting. Parity influences clitoral size, but age, height, weight, and OC use do not. PMID- 1603496 TI - Clinical usefulness of computerized colposcopy: image analysis and conservative management of mild dysplasia. AB - OBJECTIVES: The purposes of this study were to evaluate the clinical usefulness of computerized colposcopy and image analysis, to investigate the correlation between lesion size and grade of dysplasia, and to examine and record the colposcopic changes associated with progression or regression of cervical dysplasia. METHODS: Sixty-eight patients with a fully visualized squamocolumnar junction and a histopathologic diagnosis of mild dysplasia were serially monitored for a period of 1 year using computerized colposcopy and image analysis. All patients had baseline computer-assisted measurements of their cervical lesions and repeat measurements at 3-month intervals. RESULTS: The mean age of the patients was 31 years, and the mean size of the colposcopically visualized lesions was 58 mm2. During the 12-month observation, 5.9% of the lesions increased in size, 32.4% decreased in size, 13.2% remained unchanged, 20.6% disappeared, and 27.9% completely changed location. In patients with an increase in lesion size (N = 4), a repeat biopsy was performed, revealing a progression to moderate dysplasia. Treatment was withheld from patients whose lesions disappeared (N = 14), decreased in size (N = 22), or remained unchanged (N = 9). Active therapy was unnecessary in 66% of cases and repeat biopsy was avoided in 94.1%. CONCLUSIONS: Computerized colposcopy provides objective information and may be an adjunct to cytology and histopathology in some cases. Computerized colposcopy replaces subjective colposcopic evaluation with objective computer assessment and may hold promise for conservative management of cervical dysplasia. PMID- 1603497 TI - Determinants of parental decision to abort or continue after non-aneuploid ultrasound-detected fetal abnormalities. AB - OBJECTIVE: This study evaluated factors influencing the decision to abort after abnormalities in the karyotypically normal fetus were found through ultrasonography. METHODS: We reviewed all pregnancies complicated by ultrasound detected abnormalities managed on our service from April 1990 through August 1991 (N = 262). Cases with associated karyotypic abnormalities were excluded (N = 35), as were cases diagnosed after the legal gestational age limit for abortion (N = 68). The remaining 159 cases were stratified into prognosis groups of "severe," "uncertain," and "mild." RESULTS: The prognostic severity of the ultrasound abnormality strongly correlated with the decision to abort (P less than .0001). Rates of termination were 0, 12, and 66% in the "mild," "uncertain," and "severe" groups, respectively. The patients' age, gravidity, and parity, and the fetal gestational age at diagnosis did not differ significantly between the groups. CONCLUSIONS: 1) In non-aneuploid pregnancies with an ultrasound diagnosis of fetal abnormality, the major predictor of the decision to abort was the severity of fetal prognosis. 2) The gestational age at diagnosis was not an important variable in the decision to abort for fetal structural abnormalities. 3) Parents who had fetuses with abnormalities associated with uncertain prognoses usually opted to continue the pregnancy. This appeared to be particularly true for defects that were potentially correctable in utero or by neonatal intervention (even if investigational). PMID- 1603498 TI - Mortality and morbidity after intrapartum asphyxia in the preterm fetus. AB - This matched cohort study examined the significance of intrapartum fetal asphyxia determined biochemically in the preterm newborn in regard to outcome during the first year. Thirty preterm newborns with metabolic acidosis at delivery were compared with 60 preterm newborns, matched for birth weight, with normal blood gas measures. Deaths during the first year were reviewed. Assessment of the surviving children at 1 year corrected age included neurologic examination, Bayley scales, and Uzgiris and Hunt scale to define motor and cognitive development. Seven asphyxiated infants (23%) died during the first year compared with two nonasphyxiated infants (3%), a statistically significant difference (P less than .006). Among the surviving children, the incidence of minor motor and/or cognitive deficits was the same in the two groups. The incidence of major motor and/or cognitive deficits in the group with asphyxia (eight of 30) was significantly greater than in the control group (eight of 60) (P less than .03). These results indicate that intrapartum fetal asphyxia in the preterm newborn is a contributing factor to the mortality and morbidity observed in these children. PMID- 1603499 TI - Coupling of fetal movement and fetal heart rate accelerations as an indicator of fetal health. AB - OBJECTIVE: The purpose of this study was to determine the clinical value of identified coupling of fetal heart rate (FHR) accelerations (more than five beats per minute for any duration) with objectively detected fetal movements. METHODS: One hundred sixty-six patients underwent routine fetal testing using a Doppler device that recognized both FHR and fetal movements. The coupling index was determined to be the percentage of fetal movements associated with FHR accelerations, and various coupling indices were compared with nonstress test (NST) results. RESULTS: A coupling index above 25% and below 75% compared well with the traditional NST by standard epidemiologic criteria and by the kappa statistic. CONCLUSION: Coupling of even small FHR accelerations and fetal movements could substitute for or replace the NST in antenatal screening. PMID- 1603500 TI - Antenatal treatment of alloimmune thrombocytopenia. AB - OBJECTIVE: Neonatal alloimmune thrombocytopenia is caused by platelet antigen incompatibility between the mother and fetus. Affected fetuses may have severe thrombocytopenia leading to intracranial hemorrhage before or at birth. We sought to treat this condition in utero to prevent these hemorrhages. METHODS: Eighteen women who had previously delivered infants with severe alloimmune thrombocytopenia were treated with weekly infusions of intravenous gamma globulin from the diagnosis of fetal thrombocytopenia until birth; nine were also treated with corticosteroids. RESULTS: There were no intracranial hemorrhages in the treated fetuses, compared with ten cases among the 21 untreated siblings (48%). Only three treated fetuses, compared with 16 of 20 untreated siblings, had platelet counts of less than 30,000/microL, with no bleeding complications. CONCLUSION: Antenatal treatment of alloimmune thrombocytopenia with weekly gamma globulin effectively improves the fetal platelet count and prevents intracranial hemorrhage. PMID- 1603501 TI - Endothelin in maternal and umbilical cord blood in spontaneous labor and at elective cesarean delivery. AB - We measured endothelin-1, a potent vasoconstrictor peptide released by the vascular endothelium, in maternal, umbilical cord, and retroplacental blood plasma in cases of spontaneous and elective cesarean delivery. Mean (+/- standard error) endothelin-1 in the maternal plasma increased with advancing pregnancy, from 1.2 +/- 0.13 pmol/L at 32-34 weeks to 2.4 +/- 0.2 pmol/L at 38-41 weeks (P less than .01) and 3.4 +/- 0.3 pmol/L (P less than .02) during labor. Concentrations were significantly higher in umbilical cord plasma than in maternal venous plasma, and higher in the cord venous plasma after vaginal delivery (52.9 +/- 11.4 pmol/L) than after cesarean performed before the onset of labor (9.0 +/- 1.1 pmol/L) (P less than .001). In spontaneous labor, concentrations in the retroplacental blood plasma (23.3 +/- 4.5 pmol/L) were approximately ten times higher than those in the maternal peripheral blood. Levels in the umbilical cord and retroplacental blood plasma were the highest found so far in any physiologic condition, suggesting that an increased intrauterine release of endothelin-1 at delivery may promote constriction of the blood vessels in the umbilical cord and placental bed. PMID- 1603502 TI - A retrospective review of the efficacy and safety of prostaglandin E2 with premature rupture of the membranes at term. AB - OBJECTIVE: The purpose of this study was to assess rates of endometritis, clinical chorioamnionitis, cesarean delivery, and neonatal sepsis from the records of patients with premature rupture of the membranes (PROM) and an unfavorable cervix treated with vaginal prostaglandin (PG) E2 in comparison with those in the literature. METHODS: Using a computer data base at Denver General Hospital, we identified 146 women with PROM and cervical dilatation of 2 cm or less at term who were treated with PGE2 gel or suppositories. The records were reviewed to identify rates of maternal and neonatal infection and complications, as well as cesarean delivery. RESULTS: The cesarean rate was 12%. Chorioamnionitis developed in 6.8% of the study group and endometritis in 2%. Neonatal complications were limited to two with low Apgar scores (less than 7 at 5 minutes), one with microbiologically confirmed sepsis, and two with positive urine counterimmunoelectrophoresis for group B streptococcus. The only instance of neonatal sepsis occurred in a patient with rupture of membranes longer than 24 hours. CONCLUSIONS: The use of vaginal PGE2 suppositories for induction of labor and cervical ripening in term patients with PROM was accompanied by a high rate of vaginal delivery and a low rate of maternal and neonatal complications in a city hospital setting. PMID- 1603503 TI - High frequency of cytogenetic abnormalities in fetuses with cystic hygroma diagnosed in the first trimester. AB - OBJECTIVE: The purpose of this study was to evaluate the association between fetal cystic hygroma detected in the first trimester and fetal cytogenetic abnormalities. METHODS: Visualization of a prominent (2.5 mm or larger) anechoic or hypoechoic separation of the fetal skin line from the posterior body wall led to the diagnosis of fetal cystic hygroma; presence or absence of septations within the cystic hygroma was documented in each patient. Fetuses with additional structural defects were excluded from this study. All eligible women were offered prenatal cytogenetic studies (ie, chorionic villus sampling, amniocentesis). RESULTS: Cytogenetic studies were performed on all 32 affected fetuses. Fifteen of 32 fetuses (46.9%) had abnormal complements. Septations within the cystic hygroma were demonstrated in 18 fetuses; nine of these had abnormal karyotypes. Of the 12 women carrying fetuses with normal chromosome complements who elected to continue their pregnancies, 11 delivered infants with no evidence of cystic hygroma. CONCLUSIONS: Prenatal cytogenetic analysis should be offered to women with fetal cystic hygroma diagnosed in the first trimester. Normal outcome is likely in those showing no chromosome abnormalities. PMID- 1603504 TI - The association between unexplained second-trimester maternal serum hCG elevation and pregnancy complications. AB - OBJECTIVE: We conducted this cohort analytic study to determine whether women with unexplained elevations of maternal serum hCG at 16-20 weeks' gestation are at increased risk for pregnancy complications and adverse perinatal outcomes. METHODS: The inclusion criteria were a singleton gestation, a confirmed gestational age, and an hCG level greater than 2.5 multiples of the median (MOM). The exclusion criteria were fetal anomalies, an abnormal karyotype, and a maternal serum alpha-fetoprotein (MSAFP) level greater than 2.5 MOM. A group of randomly selected women with normal hCG and MSAFP levels served as controls. RESULTS: Of the 6011 women screened, 284 (4.7%) had an unexplained elevated hCG level. Patients with elevated levels of hCG had a significantly higher risk for hypertension (odds ratio 4.4; 95% confidence interval [CI] 1.9-10) and fetal growth restriction (odds ratio 2.8; 95% CI 1-7). Women with hCG levels greater than 4 MOM also had an increased risk of preterm delivery (odds ratio 3.3; 95% CI 1.3-8.2). CONCLUSION: Pregnancies with unexplained elevated hCG levels should be regarded as high-risk pregnancies and managed accordingly. PMID- 1603505 TI - Ascites: a portent of cardiopulmonary complications in the preeclamptic patient with the syndrome of hemolysis, elevated liver enzymes, and low platelets. AB - OBJECTIVE: Maternal ascites is frequently found at cesarean delivery in patients with severe preeclampsia or eclampsia expressed as hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome). We attempted to determine whether large-volume maternal ascites present at cesarean delivery in HELLP syndrome patients is correlated with disease severity or with any specific form of increased maternal morbidity. METHODS: For this retrospective case series, we reviewed the medical records of 190 patients and noted the presence or absence of large-volume maternal ascites, peripartum complications, laboratory data, and specific operative techniques. RESULTS: The incidence of large-volume ascites in patients with HELLP syndrome who underwent abdominal delivery was approximately 10% in classes 1, 2, and 3. Compared with HELLP syndrome patients without ascites, those with HELLP-associated ascites at surgery had a significant sixfold increase in the incidence of congestive heart failure and a ninefold increase in the incidence of adult respiratory distress syndrome, both of which usually became clinically apparent within 24 hours postpartum. Those HELLP syndrome patients without ascites at surgery developed congestive heart failure or adult respiratory distress syndrome infrequently, and more than 24 hours postoperatively. CONCLUSION: Cautious fluid administration and observation for cardiopulmonary deterioration are crucial in management of the critically ill, high-risk group of HELLP syndrome patients with large-volume ascites. PMID- 1603506 TI - Anticardiolipin antibodies and pregnancy outcome in women with human immunodeficiency virus infection. AB - Abnormal anticardiolipin antibodies are associated with adverse pregnancy outcome in the general obstetric population. We studied 55 pregnancies in women infected with human immunodeficiency virus type 1 (HIV-1) to examine two hypotheses: that a substantial proportion of these women would have raised anticardiolipin antibodies, and that the affected pregnancies would be more likely to be complicated by preterm delivery and intrauterine growth retardation. Blood was taken at the initial antenatal visit, and was also taken from 15 HIV-seronegative intravenous (IV) drug users and 20 controls with no drug history. The reference for immunoglobulin G class antibodies to cardiolipin was calculated from 50 healthy young adults, and the upper limit of normal was defined as 4 standard deviations above the mean for this reference series. Twenty-four percent of the infected women, but none of the HIV-seronegative IV drug users and none of the control group, had raised anticardiolipin antibodies. There was no statistically significant relationship with birth weight, standardized birth weight, length, gestation, occipitofrontal circumference, or adverse pregnancy outcome. No women gave a history of thromboembolism or recurrent abortion, and in no pregnancy was there clinically apparent thromboembolism. We conclude that abnormal anticardiolipin antibodies provoked by HIV infection are common, but probably have a narrow specificity for cardiolipin, are unrelated to phospholipid antibody syndrome, and cannot explain adverse pregnancy outcome in HIV-infected women. PMID- 1603508 TI - Bloodborne-pathogen rule assailed. PMID- 1603507 TI - The effect of minor degrees of glucose intolerance on the incidence of neonatal macrosomia. AB - The incidence of neonatal macrosomia in infants of mothers who have only one abnormal value in a 3-hour glucose tolerance test (GTT) is greater than normal. Often, corrections for gestational age have not been used in the analysis, and in the few studies in which corrections were made, the results conflicted. In this study, the birth weights of infants from 157 patients who had only one abnormal GTT value were compared with the birth weights of infants from normal mothers, with and without correction for gestational age. Analysis using three different GTT criteria revealed that the incidence of birth weight greater than 4000 g was 20% or greater in the infants of mothers who had only one abnormal GTT value and only 12.4% in controls. However, when adjusted for gestational age, there were no differences in the birth weights and percentage of large for gestational age (LGA) infants in the study groups versus controls. The mean and gestational age adjusted birth weights of the greater-than-4000-g neonates born to women with one abnormal GTT value were no different than those of controls. However, at delivery, the gestational ages of patients with one abnormal GTT value tended to be slightly greater than those of controls by 0.1-0.6 weeks, suggesting that minor degrees of abnormal glucose metabolism may prolong pregnancy in some patients. When compared with the literature, the findings of this study suggest that the National Diabetes Data Group criteria may be too high as a screen for LGA infants. PMID- 1603509 TI - 'Value' becomes important measure in judging employee healthcare costs. PMID- 1603510 TI - Meaningful AIDS education helps allay fears of working with infected employee. PMID- 1603511 TI - Guidelines to consider when buying generic drugs for worksite dispensing. United States Food and Drug Administration. PMID- 1603512 TI - Information age brings better health management. PMID- 1603513 TI - Controlling healthcare costs through a coalition cost-awareness program. PMID- 1603514 TI - Chain-of-custody errors can quickly undermine the case in court. PMID- 1603515 TI - Information a critical resource in fight against substance abuse. PMID- 1603516 TI - Managing the high cost of back injury. PMID- 1603517 TI - Safety and health director must be creative and tenacious at workplace. PMID- 1603518 TI - Spirometry, vision tests support worker health. PMID- 1603519 TI - EOHSI program is state of the art in environmental health research. PMID- 1603520 TI - Minority health issues: Hispanic Americans. PMID- 1603521 TI - What is the registered nurse's responsibility in accepting telephone orders? PMID- 1603522 TI - Get ready for mandatory continuing education. PMID- 1603523 TI - The use and abuse of nursing students. PMID- 1603524 TI - Postnatal development of the corticotectal projection from the visual cortex of the mouse. AB - The postnatal development of the corticotectal projection was investigated by injecting the axon tracer DiI into the visual cortex of mouse pups. It was found that DiI-labeled axons arrive at the ipsilateral superior colliculus and enter the optic nerve layer of this structure on postnatal days 3 and 4 (P3-P4). These corticotectal axons extend into the caudal end of the superior colliculus on P4 and give off small collateral branches that ascend vertically to the superficial gray layer. During the first two postnatal weeks, the collateral branches do not form a demarcated terminal zone, but rather diffusely spread within the superficial gray layer of the superior colliculus. These collateral branches continue to dichotomize and form a bright terminal zone within the superficial gray layer on P11. The terminal zone decreases in size during the second and third postnatal weeks, and appears to be of the same size when compared with the adult counterpart by P19. The terminal zone of the corticotectal axons from the visual cortex is established by P19. In parallel with the maturation of the terminal zone of the corticotectal projection, the distal segment of the corticotectal axons is lost during the second postnatal week. We conclude that the growing tips of the corticotectal axons do not strictly project to their future terminal zone within the superior colliculus, and 'misdirected' axons are eliminated during the early postnatal period. PMID- 1603525 TI - An additional discovery of salamanders, Salamandrella keyserlingii Dybowski, with no blood vessels in the brain parenchyma except in the olfactory bulb. AB - The brain parenchyma of Salamandrella keyserlingii Dybowski (SKD) is not vascularized except in the olfactory bulb. In the brains of SKD, neuronal and glial perikarya are seen densely aggregated at the periventricular regions and no blood vessels enter the brain parenchyma from the meningeal vessels. Former investigators have discovered no blood vessels in the brains of nine species of salamanders in the Hynobiidae, all of which inhabit Japan. This report adds one more avascular species of salamander which is found in Hokkaido, Japan. The reasons why the brain of Hynobiid salamanders is not vascularized and why only the olfactory bulbs are vascularized cannot be speculated on at the present time. PMID- 1603526 TI - Effects of starvation on the water-clear cell in the golden hamster parathyroid gland. AB - Changes of the water-clear cells of the parathyroid glands in adult and senile golden hamsters 2 and 5 days after starvation were investigated. The ultrastructure of the water-clear cells of the parathyroid glands in the starved adult and senile animals almost resembled that of the control adult and senile animals. However, lipid droplets were very numerous in the water-clear cells in the adult and senile animals after starvation. It is considered that starvation affects functional activity in the water-clear cells of the parathyroid gland. PMID- 1603527 TI - Gross anatomical observations on two cases of right-sided arch of the aorta with the left subclavian artery as its last branch. AB - Two cases of Adachi-Williams-Nakagawa type N (Krause's type II-2-B) right-sided arch of the aorta were observed gross anatomically. We discovered the first in a 67-year-old female corpse during dissection practice. The second was found in an old male patient through radiography. After his death at 87 years, angiography revealed the anomaly to be of type N. Case 2 (and case 1 after the discovery of the anomaly) were dissected outside of regular dissection practice. Neither belonged to the "circumflexus" type and in each case the ligamentum arteriosum was located on the left, forming a vascular ring. However, only case 1 exhibited marked constriction of the esophagus, explaining the dysphagia that she had suffered. This deviation was evidently caused by projection of the aortic diverticulum of case 1 in front of the vertebral column (since the origin of the descending aorta was located at a more antero-medial position in case 1 than in case 2) and narrowness of the vascular ring of case 1. On both sides in both cases, the second posterior intercostal arteries were branches of the thoracic aorta. This indicated that the high position of the arch of the aorta in both cases (the uppermost point was at the level between Th1 and Th2) is an anomaly, being not limited only to the arch of the aorta. All bronchial arteries originated from the thoracic aorta. These have not been described in association with examples of right-sided arch of the aorta, and were therefore compared against a mirror image of the normal aorta described by Kasai. However, some discrepancies were still noted. Among the veins, the left brachiocephalic vein of case 2 was partially occluded, forming collateral circulation behind the ascending aorta. In both cases, the thoracic duct ascended on the left of the thoracic aorta, passed behind and then above the left subclavian artery, and joined the left angulus venosus. In addition, the azygos vein, recurrent laryngeal nerve, and cardiac nerves are described. PMID- 1603528 TI - Branches of the internal thoracic artery of rats supplying the heart, the sinus regions and the brachiocephalic veins. AB - Branches of the internal thoracic artery (ITA) of rats which supply the heart, the sinus regions (see Terminology 1) and the brachiocephalic veins, were macroscopically studied. Two major branches of the ITA, the pericardiacophrenic artery and the descending ramus of the bronchoesophageal artery, were found supplying branches to these central portions of the cardiovascular system (see Table 1). They constituted, together with the ordinal coronary arteries, a system of dual blood supply to the heart as reported by Grant & Regnier (1926), Halpern et al. (1953, 1954) and Hebel & Stromberg (1986). This finding also supports a proposal of Grant & Regnier (1926) that the rat ITA emits cardiac branches which should be classified on the vertebrate scale to the caudal or extracoronary artery. Branches of the ITA to the heart, the sinus regions and to the brachicephalic veins were found to be classified into 2 major groups depending on their choice of entrance--arterial portal and venous porta; the latter was further divided into 3 subgroups depending on their selection of the (lateral or pulmonary or esophageal) mesocardium for traveling to the venous porta (see Table 2). PMID- 1603529 TI - Ten-year follow up comparing anterior and posterior chamber intraocular lens implants. AB - Results achieved in eyes following a single surgeon's first 200 procedures consisting of intracapsular cataract extraction and implantation of a Choyce Tennant anterior chamber lens (AC-IOL) (1977 to 1980) are compared with those achieved following the same surgeon's first 200 procedures consisting of extracapsular cataract extraction and implantation of a posterior chamber intraocular lens (PC-IOL) (1980 to 1982). For the AC-IOL eyes, follow up ranged from 11.1 to 14.2 years (mean, 12.0 years); for the PC-IOL eyes, from 9.5 to 10.8 years (mean, 10.0 years). The AC-IOL eyes had many early problems: pupillary block (7%), iritis (15%), and secondary glaucoma (8%). Four percent developed corneal edema, 1.5% vitritis, and 2% localized iris holes under the lens. Ectropion uveae appeared in 8.5%, indicating some ongoing inflammation. One and one-half percent of these lenses were removed or exchanged. Seventy-nine and one half percent of these eyes had 20/40 or better vision at 10 years; 4% had visual loss along with corneal edema or vitritis, apparently related to the AC-IOLs. The PC-IOL eyes had comparatively few lens-related complications: 1% corneal edema, 1.5% iritis, 1% vitritis, and 2% secondary glaucoma. Some localized trapping of the pupil occurred in 8%. One percent of the PC-IOLs were removed, and 1% decentered, requiring McCannell sutures. Final visual acuity at 10 years was 20/40 or better in 77.5%. None of the PC-IOL eyes had decreased vision related to the lens implant. PMID- 1603530 TI - Peripheral anterior synechiae formation with anterior chamber intraocular lenses. AB - In a cross-sectional study, 88 eyes with anterior chamber intraocular lenses (AC IOLs) were evaluated by goniophotography by one masked observer for the presence of peripheral anterior synechiae (PAS) and by another masked observer for the length of the AC-IOL. Sixty-eight of the 88 lenses had PAS which were strongly correlated with the lens being oversized (P less than .001). However, differences in haptic style or lens rigidity were not associated with the presence of PAS. PMID- 1603531 TI - Transsclerally-fixated posterior chamber intraocular implants without capsular support in penetrating keratoplasty. AB - The results of 36 patients who underwent penetrating keratoplasty with transscleral fixation of a posterior chamber intraocular lens are reviewed. A 13.75-millimeter "Revlens," which has the configuration of an open-loop anterior chamber lens, was used in all of the cases and gave good stability in the ciliary sulcus. The 10-0 Prolene sutures used to secure the implants were burrowed through the sclera and exited sufficiently far from the limbus to be adequately covered by Tenon's capsule and conjunctiva. No sutures eroded through the conjunctiva or needed to be removed. Two grafts became opaque, one from rejection and the other from uncontrolled glaucoma. No vitreous hemorrhage or retinal detachment occurred. Ten patients (27.8%) had cystoid macular edema diagnosed either before or after surgery; three had age-related macular degeneration; and two had traumatic macular scars. Sixteen eyes (44.4%) had final visual acuities of 20/40 or better and 25 (69.4%) saw 20/200 or better. Mean follow up was 16.8 months (range, 9 to 36 months). PMID- 1603532 TI - Disruption of the blood-aqueous barrier by residual lens epithelial cells after intraocular lens implantation. AB - We performed a clinical study to confirm whether and how residual lens epithelial cells (LECs) participate in postoperative pseudophakic inflammation, including fibrin reaction. Twenty-six eyes of 13 patients with bilateral cataracts were treated by phacoemulsification and posterior chamber intraocular lens (PC-IOL) implantation. In the eye from which LECs had not been removed, the aqueous flare was measured with a laser flare-cell meter. Flare decreased from an initial peak, increasing again to form a flare spike when LECs came into contact with the PC IOL and began to undergo fibrous proliferation at 6 to 14 days after surgery. The spike was evidence that the blood-aqueous barrier had been disrupted again. Fibrin reaction developed in two eyes. In the other eye of each pair, from which LECs had been removed by ultrasound aspiration, neither a flare spike nor fibrous proliferation was noted. We conclude that residual LECs break down the blood aqueous barrier as they proliferate and are involved in postoperative pseudophakic inflammation. PMID- 1603533 TI - Complications of secondary surgical capsulotomy in pseudophakic and aphakic eyes. AB - A retrospective study was conducted to analyze the complications of surgical capsulotomy in 587 eyes--51 aphakic and 536 pseudophakic. Transient or permanent complications occurred in 20 (3.4%). One eye was seriously damaged by perforation during retrobulbar anesthesia, and another eye was lost due to endophthalmitis. Endophthalmitis developed in two other eyes, but it readily resolved with medication. Two eyes had markedly elevated intraocular pressure (IOP) (greater than 35 mm Hg), which was associated with the presence viscoelastic material in one eye; in the other eye, elevated IOP was the result of vitreous blocking of the pupillary aperture. Retinal detachments developed in nine patients (eight of whom, a significant number [P = .006], were males). Apart from the eyes in which endophthalmitis developed, all were markedly quiet after the procedure, and pressure elevation was not significant. PMID- 1603534 TI - A surgical method to repair leaking filtering blebs. AB - Surgical revision of a chronically-thinned filtering bleb with a leak at the limbus is described. After surgical excision of the scarred cystic conjunctiva and Tenon's fascia surrounding the leaking bleb, relatively uninvolved conjunctiva and Tenon's fascia are mobilized with the help of a large relaxing incision in the superior fornix and sutured over the area of filtration. We have used this technique successfully in five cases to provide fresh tissue to repair the bleb leak and restore adequate filtration. PMID- 1603535 TI - Encapsulated filtering bleb and subconjunctival 5-fluorouracil. AB - Filtering bleb encapsulation (BE) involves fibroblast proliferation and collagen synthesis. We analyzed the effect of 5-fluorouracil (5-FU) on the inhibition of BE. Forty-one patients with primary open-angle glaucoma underwent trabeculectomy in one eye as an initial surgery. Twenty-one of these eyes, randomly chosen, were treated postoperatively with four to six 5-FU subconjunctival injections over 10 days to inhibit bleb scarring; the remaining 20 eyes did not receive 5-FU. After 12 to 24 months, the surgical success rate was significantly higher in the treated eyes (P less than .05). However, the incidence of BE was similar: two eyes (9.5% and 10%, respectively) in each group. The difference between the effect of 5-FU in the inhibition of BE and bleb scarring suggests that the characteristics of the two fibroblast populations are heterogeneous. PMID- 1603536 TI - Correlation of full-thickness corneal wound length with endothelial cell loss. AB - We studied 12 patients who had sustained penetrating corneal lacerations with corneal wound lengths ranging from 1 to 9 mm to determine whether wound size was directly proportional to endothelial cell loss 3 or more months after injury. Endothelial cell counts in the uninjured eye averaged 2973 +/- 330 cells/mm2 (range, 2500 to 3700). In the injured eye, near the wound (less than 2 mm from the wound), the cell counts averaged 1260 +/- 590 cells/mm2 (range, 575 to 2500); away from the wound, where cells appeared healthiest, counts averaged 1619 +/- 544 cells/mm2 (range, 850 to 2750). The average total cell loss near the wound was 1713 +/- 622 cells/mm2 (range, 500 to 2575), vs 1354 +/- 582 cells/mm2 (range, 250 to 2150) away from the wound, compared with the uninjured eye. Cell loss near the wound was not significantly different from that away from the wound. There was a positive correlation between wound length and total cell loss measured both near the wound (r = 0.830) and away from the wound (r = 0.755). Pars plana lensectomy was not associated with detectable additional cell loss. Our results suggest that patients with corneal lacerations sustain significant endothelial cell loss, which correlates closely with wound length, and that patients with larger wounds may be at greater risk for developing corneal decompensation with additional procedures or trauma. PMID- 1603537 TI - Electron microscopic appearances of human corneal endothelium following Nd:YAG laser iridotomy. AB - We looked at the electron microscopic appearances of the corneal endothelium following neodymium:YAG (Nd:YAG) laser iridotomy in a patient with a shallow anterior chamber. An area of denuded endothelial cells approximately 500 microns in diameter was produced when no contact lens was used. The area of cell loss was reduced by approximately 50% when an Abraham YAG goniolens was used. We conclude that the use of a positive plus contact lens can help minimize cell loss following Nd:YAG laser iridotomy. PMID- 1603538 TI - Transcanalicular THC:YAG dacryocystorhinostomy. AB - Chromium-sensitized and thulium- and holmium-doped YAG lasers (THC:YAG laser) were used to create a nasal bony ostium in the area of the lacrimal sac fossa in four fresh frozen bisected human cadaver heads. The lasers-long pulsed (300 milliseconds), compact, self-contained, and solid state--operate in the near infrared (2.1 microns). The opening was created by passing the 320-micrometer laser fiber across the canalicular system. Pulse energies of 250 to 900 mJ were used with a repetition rate of 5 to 15 pulses per second. Energy levels ranging from 1.25 to 9 W produced a full-thickness bony ostium approximately 3 to 4 mm in diameter. Silicone tubing was then threaded through the superior and inferior canaliculus system in the standard fashion. This technique may simplify conventional dacryocystorhinostomy as well as endonasal laser dacryocystorhinostomy procedures. PMID- 1603540 TI - Oblique orientation of incisions in four-incision radial keratotomy. PMID- 1603539 TI - Prediction of visual acuity recovery in cystoid macular edema. AB - Three consecutive patients participated in a prospective evaluation of pseudophakic cystoid macular edema. The duration of the macular edema ranged from 6 to 8 months. On the initial visit, the best corrected acuity with spectacles was determined and a potential acuity meter reading was obtained; this test suggested potential for visual recovery in two of the three patients. Sub-tenon's injections of methylprednisolone acetate (20 mg) were administered along with topical 1% prednisolone acetate and 1% atropine. One month later, visual acuity was improved by more than 2 Snellen lines in all three of the patients. A visual acuity measurement with the potential acuity meter that is better than the best corrected acuity with spectacles may reflect the presence of intact, but dysfunctional photoreceptors that are capable of restoring visual acuity upon resolution of the edema. PMID- 1603541 TI - Incidence of inadvertent perforation in strabismus surgery. AB - We conducted a prospective study for over 2 years to determine the incidence of perforations following strabismus surgery. All eyes were examined by indirect ophthalmoscopy and indentation immediately after surgery in an attempt to identify perforation sites. No cryotherapy or treatment was done. None of the 10 perforations identified was associated with retinal detachment or endophthalmitis. The incidence of perforations was 2.8% on a per-case basis and under 1% on a per-muscle basis. PMID- 1603542 TI - Tissue plasminogen activator irrigation to facilitate removal of subretinal hemorrhage during vitrectomy. AB - I report removing a large submacular hemorrhage by means of vitrectomy combined with use of tissue plasminogen activator (tPA) to facilitate clot removal. Four months postoperatively, the vision was 20/100 and the retina was flat, with a very thin layer of residual hemorrhage and pigmentary alteration in the macula. Although the long-term prognosis is guarded, this case does suggest that tPA may be a useful adjunct in managing selected cases of subretinal hemorrhage associated with macular degeneration. PMID- 1603543 TI - Probe orientation in contact Nd:YAG laser cyclophotocoagulation. AB - We investigated the effect of the angle orientation of the probe during Nd:YAG transscleral cyclophotocoagulation. We found, based on histologic evaluation of the ciliary processes and surrounding structures, that the angle at which the probe was placed on the eye was critical. A probe angulation as little as 15 degrees off the perpendicular destroyed sites less than optimal for achieving the goal of decreasing aqueous humor production. PMID- 1603544 TI - Corticosteroid vehicle toxicity. PMID- 1603545 TI - Tarsal strip procedure. PMID- 1603546 TI - Corneal traction suture vs mattress-type episcleral suture. PMID- 1603547 TI - Bacillus endophthalmitis. PMID- 1603548 TI - Reproducibility of data from a hand-held digital pulp tester used on teeth and oral soft tissue. AB - Controlled studies of the reproducibility of data from electronic pulp testing instruments are limited and contain few statistical analyses. The reproducibility of these readings is important if the instrument is to be used for determining differences in sensitivity. Twenty human subjects (16 male) were used in this study. One incisor, one premolar, one molar tooth with small or no restorations, and two gingival soft tissue positions from each upper and lower arch of each subject were stimulated with the Analytic Technology vitality scanner. This procedure was repeated twice with a 5-minute rest between each trial, for a total of three trials. Each subject was then seen again after a period of at least 3 days, at which time the trials were repeated. The collected data were grouped by trial, tooth position, and day. Paired t test analysis of both the absolute difference between any two trials on the same day and the average of the absolute differences between corresponding trials on days 1 and 2 showed no statistically significant differences (p greater than 0.05). Accommodation to the stimulus was evaluated by examining differences in the mean values between the three same-day trials. The Analytic Technology vitality scanner was found to be reproducible both for consecutive same-day trials and for corresponding trials on different days. No same-day trends in meter readings were noted. PMID- 1603549 TI - Oral radiographs in the detection of early signs of osteoporosis. AB - A study was conducted to determine whether radiographic changes could be detected in the mandible of patients with mild-to-moderate postmenopausal osteoporosis and whether these changes could be used as a diagnostic tool to differentiate normal from osteoporotic patients. Subjects were classified as either osteoporotic (21) or normal (14) on the basis of bone density measurements of the lumbar spine and femoral neck, as determined by dual-photon absorptiometry. Mandibular bone density measurements were made on panoramic and periapical radiographs and expressed in terms of millimeters of aluminum equivalent. Thickness of the cortex at the angle of the mandible, sinus floor, and lamina dura of the tooth socket was also measured. There were no significant differences in any of the mandibular measurements between the normal and osteoporotic subjects. Whereas the skeletal bone measurements were correlated with each other, there was no correlation between skeletal and mandibular bone measurements. Women with mild-to-moderate osteoporosis could not be distinguished from women with normal bone density with the method described in this article. PMID- 1603550 TI - Prevalence of osseous changes in the temporomandibular joint of asymptomatic persons without internal derangement. AB - There is a controversy in the literature regarding the prevalence of osseous changes in the temporomandibular joint (TMJ) of asymptomatic persons. Using cephalometrically corrected tomograms, we assessed one TMJ of each of 34 asymptomatic persons who had no arthrographic or magnetic resonance imaging evidence of internal derangement. Minimal flattening of the condyle or articular eminence was seen in 12 joints (35%). More advanced osseous changes such as erosion, osteophytosis, or sclerosis were not seen in any joint. The findings suggest that generally no osseous changes occur in the TMJ in asymptomatic persons without internal derangement. When osseous changes occur, they are confined to minimal flattenings. Minimal flattening is probably of no clinical significance because the persons were asymptomatic, and arthrography and magnetic resonance imaging showed no evidence of abnormalities in the soft tissues. PMID- 1603551 TI - Idiopathic bone cavity on the posterior buccal surface of the mandible. AB - A cavity on the posterior buccal surface of four dry mandibles (n = 8282) is reported. The shape, size, unilaterality, and sex distribution of this phenomenon are similar to anterior and posterior idiopathic bone cavities (i.e., defects) on the lingual cortex. Posterior buccal mandibular defects differ from posterior lingual cavities in their unilateral occurrence and age distribution. The differential diagnosis for posterior buccal mandibular defects includes an anatomic variant, an aneurysmal erosion, erosion by a lymphoid nodule, and a neural neoplasm. PMID- 1603552 TI - Multiple supernumeraries of different tooth generations. PMID- 1603553 TI - Parotid duct swelling: calculated to confuse. PMID- 1603554 TI - Shedding of a permanent tooth. PMID- 1603555 TI - Detached root apexogenesis. PMID- 1603556 TI - The modified superiorly based pharyngeal flap. Part IV. Position of the base of the flap. AB - The modified superiorly based pharyngeal flap surgical technique developed by Epker et al. was performed on 13 patients with moderate to severe hypernasality. The flap base was attached close to the level of the palatal plane and was found to maintain a consistent longitudinal relationship to the level of the atlas. This technique corrected hypernasality in a range of patients with velopharyngeal incompetence, as predicted. PMID- 1603557 TI - Double condyles. PMID- 1603558 TI - Fused supernumerary microdont. PMID- 1603559 TI - Bizarre egg-shaped shadow of parapharyngeal space. PMID- 1603560 TI - Anatomic placement of fixation devices in genioplasty. AB - The form of the anterior mandible in 45 patients was assessed before, immediately after, and 1 year after genioplasty. A specific, consistent pattern of bone apposition and resorption was observed after advancement genioplasty. A consistent but inverse apposition-resorption pattern was observed after reduction genioplasty. In view of the observed pattern of bony change, it is recommended that fixation devices for genioplasty be placed in areas of future bone deposition. PMID- 1603561 TI - Gaucher's disease: case report of mandibular trauma. AB - Gaucher's disease is a disturbance of lipid storage that results in the accumulation of histiocytes filled with glucosyl ceramide in various organs and bones. Clinical features include history of epistaxis, hemoptysis, and spontaneous gingival hemorrhage. This article reviews Gaucher's disease with reference to its importance to dental practitioners and a case involving mandibular trauma is presented. PMID- 1603562 TI - Myositis ossificans of medial pterygoid muscle. A cause for temporomandibular joint ankylosis. AB - An unusual case of myositis ossificans of the medial pterygoid muscle has been discussed. It is important to know the exact cause of the temporomandibular joint ankylosis, for successful treatment. Computed tomographic scan and panoramic radiographs are essential diagnostic aids for evaluating conditions such as myositis ossificans. Myositis ossificans can be one of the causes of extra articular temporomandibular joint ankylosis. PMID- 1603563 TI - Prevalence of predisposing factors for endocarditis among an elderly institutionalized population. AB - The charts of 100 nursing home patients in a Veterans Affairs skilled nursing facility were reviewed to identify the need for endocarditis prevention prior to dental procedures. Forty-two (42%) had identifiable needs. Systolic murmurs, documented in 38% of the residents, were the most prevalent abnormality. Five patients had other indications for antibiotic coverage (history of rheumatic heart disease, previous endocarditis, artificial heart valve), which added four unique patients (those not already identified by murmurs) to the total. The dental implications of these findings are discussed. PMID- 1603564 TI - Efficacy of etretinate (Tigason) in symptomatic oral lichen planus. AB - This study evaluated the maximum permitted dosage of etretinate (75 mg/day) as the first mode of systemic treatment of patients with symptomatic oral lichen planus. Six patients were treated and examined objectively and subjectively every 2 weeks for 2 months. At the end of the study 50% of patients reached an asymptomatic stage; improvement of clinical signs and symptoms was noted in all patients. However, on reevaluation 2 months after treatment was discontinued some clinical signs of recurrence were seen in all patients. Further follow-up for more than a year showed that the patients had reverted to the same frequency of recurrence as before the systemic use of etretinate. PMID- 1603565 TI - Oriental sore: a case report. AB - We report a typical case of an oriental sore (cutaneous leishmaniasis) in a 28 year-old patient. The lesion was located on the upper lip, causing macrocheilia and an esthetic problem to the patient, who required urgent treatment. N Methylglucamine antimonate proved to be an effective, well-tolerated drug. PMID- 1603566 TI - Lipoma of the floor of the mouth. AB - A case of lipoma of the floor of the mouth presenting as an acute swelling in a 72-year-old man is reported. The clinical presentation and differential diagnosis are discussed. PMID- 1603567 TI - Central odontogenic fibroma, WHO type. A report of three cases with an unusual associated giant cell reaction. AB - Three cases of central odontogenic fibroma, WHO type, that exhibited a prominent giant cell granuloma-like histopathologic component are described in this report. All three lesions occurred in women, and all were located in the mandibular premolar-molar region. One lesion recurred after conservative excision, and the recurrence displayed the two histologically distinct tissues of the original lesion. The authors think that this pathologic process does not represent a "collision lesion" but, instead, is a unique presentation of a central odontogenic fibroma, WHO type. PMID- 1603568 TI - Evaluation of epidermal growth factor receptor in squamous cell carcinoma of the oral cavity. AB - Forty-seven cases of oral squamous cell carcinoma were examined immunohistochemically by the avidin-biotin peroxidase complex method with anti epidermal growth factor (EGF) receptor mouse monoclonal antibody, and 24 cases (51%) were shown to have EGF receptor-positive cells. Correlation was strong between presence of EGF receptors and differentiation; the EGF receptor-positive cells were differentiated, whereas poorly differentiated tumors exhibited less intense staining. EGF receptor gene and c-erb B-1 by Southern blot analysis disclosed that one of 25 cases of squamous cell carcinoma exhibited a fourfold amplification of the gene. PMID- 1603569 TI - Palisaded encapsulated neuroma of oral mucosa. AB - The palisaded encapsulated neuroma is a solitary, small peripheral nerve lesion that occurs primarily on the facial skin of middle-aged adults. We report a series of 13 cases of palisaded encapsulated neuroma occurring on oral mucosa. The lesions presented as solitary, firm, sessile, partly or completely encapsulated, 2 to 3 mm nodules in adults with a mean age of 51 years (median 55 years). Nine of the neuromas occurred on the hard palate; the remainder were found on the soft palate, lower lip mucosa, upper lip mucosa, and maxillary anterior alveolar ridge. None of the cases was associated with neurofibromatosis or multiple endocrine neoplasia syndrome type III. Microscopically, the tumors were characterized by a moderately cellular, fascicular proliferation of spindle cells that showed some areas of nuclear palisading, suggestive of schwannoma. Immunohistochemical stains revealed that the lesions were composed largely of S 100 protein-positive Schwann cells and variable numbers of peripheral nerve axons, which were identified by their positive neurofilament staining. The fibrous capsule of the lesions showed positive staining for epithelial membrane antigen, indicative of perineurium. PMID- 1603570 TI - Trabecular and solid-cribriform types of basal cell adenoma. A morphologic study of two cases of an unusual variant of monomorphic adenoma. AB - Monomorphic adenomas are a morphologically complex group of salivary gland tumors. Two unusual examples, one a trabecular and the other a solid form of basal cell adenoma, reveal the development of a cribriform growth pattern focally in the former example and diffusely in the latter. They illustrate the potential for cellular differentiation within this subgroup, organization of synthetic products by the tumor cells, and the histologic criteria useful for the distinction of basal cell adenoma from adenoid cystic carcinoma. PMID- 1603571 TI - Solitary infantile myofibromatosis of the mandible. Report of three cases. AB - Infantile myofibromatosis (IMF) is a benign localized (solitary) or generalized (multicentric) proliferation of fibroblastic tissue occurring exclusively in infants and children. Three cases of solitary IMF involving the posterior region of the mandible of young children are reported. These lesions manifested clinically as asymptomatic bony expansion and roentgenographically as circumscribed lytic areas. Microscopically these tumors showed a distinct zoning phenomenon of curving bundles or intertwining fascicles of plump, spindle-shaped cells at the periphery and solid sheets of less differentiated round cells in the center. Positive immunostaining for vimentin and actin, with the lack of desmin and S-100 protein reactivity, confirmed their myofibroblastic nature of these cells and supported the diagnosis of IMF. All three lesions were treated by curettage and the follow-up showed no incidence of recurrence or any other complications. As we demonstrate in these case reports, IMF should be included in the differential diagnosis of spindle cell neoplastic processes in children. PMID- 1603572 TI - Disk derangement and inflammatory changes in the posterior disk attachment of the temporomandibular joint. A histologic study. AB - Temporomandibular joint disk derangements were investigated in 42 patients (47 joints) with respect to occurrence and degree of histologic inflammation in the posterior disk attachment and compared with reference material obtained at autopsy. Sensitivity and specificity for arthroscopy versus macroscopic observation at arthrotomy in regard to inflammation were also investigated. On histologic examination, inflammation was found in 1 joint (5.5%) in the reference material and 30 joints (64%) in the patients where pronounced inflammation was found in 6 joints (20%). Arthroscopy revealed inflammation more accurately (sensitivity 0.94%, specificity 0.86%) than macroscopic observation at arthrotomy (sensitivity 0.58%; specificity 0.90%). PMID- 1603573 TI - Resistance to fracture of endodontically treated roots. AB - The root canals of 48 single-canal canine teeth were prepared by four different methods. The coronal lingual wall and root canal space were lowered to 2 mm below the buccal wall of the roots. The prepared root was placed into acrylic resin so that 12 mm of buccal root was exposed. A slowly increasing force was applied at the junction of the buccal wall and root canal space until fracture occurred. The force of fracture of the buccal root wall of each root was recorded and the results in each group were compared. All teeth fractured at the buccal wall/acrylic resin junction. Instrumentation of the root canals significantly weakened the roots. Obturation of the canals in conjunction with Roth's 801 sealer did not strengthen the roots. Obturation of the canals in conjunction with a glass ionomer sealer significantly strengthened the roots as compared with roots instrumented but not obturated and those obturated with gutta-percha and Roth's 801 Sealer. PMID- 1603574 TI - National Demonstration Project and Joint Commission forums celebrate successes and address future needs in quality improvement, II: Joint Commission's fourth annual National Forum on Health Care Quality Improvement. PMID- 1603575 TI - A roundtable discussion: hospital leaders discuss QI implementation issues. AB - To address critical questions regarding the practical application of quality improvement (QI) concepts within health care, the Joint Commission visited six hospitals that have been implementing QI for several years. After the site visits, the leaders of these hospitals participated in a roundtable discussion of QI issues. The discussion centered around nuts-and-bolts topics, such as leadership, implementing QI, barriers/resistances, medical staff involvement, cultural change, institutionalizing QI, and external environment. The roundtable discussion is excerpted in full from a new book, Striving Toward Improvement: Six Hospitals in Search of Quality, which tells the stories of the six hospitals and their transitions to QI. PMID- 1603576 TI - A protocol for evaluation of lumbar diskectomy: a second study. PMID- 1603577 TI - Geographic variation in lumbar diskectomy: a protocol for evaluation. AB - In 1989 the Maryland Hospital Association (MHA) began developing a protocol related to lumbar diskectomy, a procedure with widely reported geographic variation in its use. The MHA's Laminectomy Advisory Committee drafted three criteria for performance of lumbar diskectomy and also developed a data collection instrument with which the eight hospitals participating in a pilot study could abstract the necessary data from medical records. Both individual hospital and aggregate results showed wide variation in compliance with the criteria. These findings suggest research and development activities such as refinement of the data-collection instrument, use of the protocol for bench marking, further investigation of clinical and other determinants of rate variation, and study of the effect of new diagnostic technology on utilization rates for this procedure. PMID- 1603578 TI - [A strategy for the diagnosis of thyroid function]. AB - The characteristics of thyroid function tests are analysed. The author stress the importance of the right strategy for investigating thyroid function in the view of expenses, labor and time consuming tests. The guidelines of American Thyroid Association for use of laboratory tests are presented. Finally there is published another investigating protocol, which can be applied for our domestic situations. PMID- 1603579 TI - [Coronary surgery at the Cardiovascular Surgical Clinic (1976-1990)]. AB - In the Cardiovascular Surgical Clinic of the Semmelweis Medical University of Budapest the first coronary artery bypass grafting (CABG) procedure was performed in 1975. Since that time coronary artery surgery has become a routine everyday practice representing more than half of the total workload of adult cardiac surgery. The analysis of 1347 operations performed between 1976-1990 on patients with coronary heart disease showed the followings: the first few years--so called learning curve of CABG operations is characterised by high mortality. With passing time the number of cases performed each year increased rapidly and the surgical technique has improved too. At the same time the operative mortality figures showed decreasing tendency--it was 2.1% for the last 609 cases. All observed parameters showed some progress: in 1990 the average number of grafts per patient was 3.09, internal mammary artery usage 15 percent and the mean aortic cross clamp time per anastomosis 24.5 minutes. Complete myocardial revascularisation is the key point of coronary artery surgery. In order to achieve this target in all operated cases further technical improvement is necessary. PMID- 1603580 TI - [Glycosylated proteins, blood sugar levels and postnatal growth in very low birth weight (less than 1500 g) neonates]. AB - The concentration of HbA1c, glycosilated serum proteins and blood glucose were followed up during the first eight postnatal weeks in 10 preterm babies of mean (+/- SD) birthweight and gestational age of 1259 +/- 140 g and 30.2 +/- 2.0 weeks, respectively. Both blood glucose and the glucosilation of proteins remained unchanged over the study period. No relationship was found either between growth rate and blood glucose level, or the latter and HbA1c concentration. Statistically significant correlationship could be observed between carbohydrate and total calorie intake and growth rate, but only during the first four postnatal weeks. PMID- 1603581 TI - [Diagnostic value of CA 19-9 and CEA in gastrointestinal pathology]. AB - The diagnostic values of CA 19-9 and CEA were evaluated in 187 cases (including 31 gastric, 41 colorectal, 12 pancreatic, 7 hepatobiliar and 5 hepatocellular carcinomas). These tumor markers were compared to the other laboratory parameters [hemoglobin, erythrocyte sedimentation rate, serum bilirubin, ASAT (aspartate amino transferase), ALAT (alanine amino transferase) GGT (gamma glutamil transpeptidase), ALP (alkaline phosphatase)]. The specificity of CA 19-9 was 89.5%, while the sensitivity of this tumor markers was 91.7% in pancreatic carcinoma, 54.8% in gastric carcinoma and 43.9% in colorectal carcinoma. The sensitivity of CEA only in colorectal patients was higher than that of CA 19-9 (specificity 73.9%, sensitivity 64.5%). Although the CA 19-9 and CEA are not known to give any cross-reaction with each other, simultaneous measurement and evaluation of these two tumor antigens did not result in a better diagnostic sensitivity. After undergoing a gastrointestinal carcinoma operation, CA 19-9 indicated the appearance of tumor recidiva with a 62% sensitivity. Calculated together with CEA the sensitivity elevated to 88.9%. In most of the patient with benign cholostasis, the CA 19-9 and CEA values were out of the normal range (53.3% and 36.4% respectively), so these tumor markers are not suitable to differentiate between benign and malign cholostasis. According to the authors, CA 19-9 is the most useful diagnostic tool to differentiate between pancreatic carcinoma and pancreatitis chronica (both group without cholostasis), as well as for monitoring the patients after surgery of a gastrointestinal cancer. PMID- 1603582 TI - [Actinomycosis with abdominal manifestation]. AB - During the last 4 years the authors observed 3 actinomycotic cases with abdominal localization. The disease was found in all the three cases to be localized to those parts of the intestinal tract where stasis of fecal contents may occur, i. e. to the appendix, to Meckel's diverticle and to the left colonic flexure. The relatively rare incidence and preoperative diagnostic difficulties make publication of these cases worthwhile. Based on own experience and literary data they describe natural history, clinical picture, histology and treatment of the disease, respectively. PMID- 1603583 TI - [Cytokine production in systemic lupus erythematosus]. PMID- 1603584 TI - [How should retired authors publish?]. PMID- 1603585 TI - [Treatment of postmenopausal osteoporosis with low doses of calcitonin and a calcitonin-anabolic combination]. AB - Menopausal osteoporotic women (age: 49-69, mean: 59.5 years) with crush fractures of the spine were treated with low doses of calcitonin (Miacalcic, 350 U/month), or with calcitonin + anabolic steroid (Retabolil, 50 mg/month). Efficacy of the therapy was controlled by single foton absorptiometry of midshaft and distal radius, by X-ray morphometry and by registering new crush fractures of the spine. Calcitonin monotherapy stopped further bone loss for two years, but at the end of the third year both absorptiometric values, as well as the radiomorphometrical index of the lumbar spine decreased significantly. In patients on calcitonin+anabolic steroid the decrease was just significant and only at radius midshaft, while at the other measured sites it was not. Two new crush fractures per 1396 patient-months occurred. Intermittent administration of low-dose calcitonin, especially together with an anabolic steroid seems to be a safe and effective therapy in established osteoporosis. PMID- 1603586 TI - [Results of extended resection of tumors of the colon and rectum]. AB - The postoperative lethality and 5 year survival of elective extended colon resections in 59 locally advanced colorectal tumour cases has been evaluated. The operation has been extended for one adjacent organ in 47 (Groups I.) and for two or more organs in 12 cases (Groups. II.). The postoperative lethality was 47/1 and 12/2 respectively (P less than 0.01). However the 5 year survival proved to be similar--42% and 40% respectively in both patients group. The 5 year survival of patients group I. and II. was not significantly different comparing to the "simple" elective colorectal resections on the patients in Dukes C stadium operated on in the same period of time. Significantly better 5 year survival has been observed in the patients groups. I. and II. comparing to the outcome of the elective palliative (anus prae and ileo- or colo-colostomies) colorectal operations. The results certify the value of the radical surgical procedures in the locally advanced tumor cases. PMID- 1603587 TI - [Prenatal diagnosis of cystic fibrosis by mutational analysis]. AB - The authors give a review about the latest method of the prenatal diagnosis of cystic fibrosis. Examples were chosen from their own cases to illustrate the possibilities of the prenatal diagnosis based on the mutation analysis of the CFTR gene. Using both mutation and haplotype analysis, 10 prenatal diagnosis were performed from chorionic villus samples taken in the early stage of the pregnancy (10-12 weeks). There were 5 healthy and 5 affected fetuses found. The advantage of this method, that in certain cases, diagnosis is available for families having no live affected child. PMID- 1603588 TI - [Percutaneous transluminal angioplasty in atypical aortic coarctation in an adult patient]. AB - In the reported case, coarctation of the aortic arch (Coa) was the cause of hypertonia. Coa diminishes the expected lifetime, and operative treatment is required. PTA is contradictory in the treatment of coarctation. In the reported case coarctation was located on the aortic arch, and because of the risk of the operation PTA was performed. The dilatation was successful, hypertension resolved, and there was no significant difference in the blood pressure on the extremities. 16 months after the dilatation the patient is symptomless. The result of this case indicates that PTA of the Coa of the aorta is feasible. More experience is needed to establish its role. PMID- 1603589 TI - First public report for physicians due this summer. AB - Public reporting of physician-specific information by the Pennsylvania Health Care Cost Containment Council begins this summer with the release of a report of physician-specific surgical data. Physicians should be aware that the release of such information may have a significant impact on decisions made by patients or potential patients. PMID- 1603590 TI - Health views from the Senate. Interview by Maria T. Montesano. AB - The state legislature is comprised of a mixture of personalities and viewpoints. In this first of a series of three interviews with members of the general assembly, Senators John Peterson and J. Doyle Corman talk about life in rural Pennsylvania, what physicians can do to be more involved in the political process, and a number of other issues. PMID- 1603591 TI - Lobbying: the best kind can be self-taught. AB - The Pennsylvania Medical Society pays professional staff to lobby for its members, as do almost all specialty groups in each state and in Washington, DC. Paid lobbyists have specific legislative responsibilities, but their efforts cannot be the only ones put forth on behalf of physician interests. PMID- 1603592 TI - Understanding CLIA '88. AB - New regulations under the Clinical Laboratory Improvement Act of 1988 have been finalized, but not without objection from the State Society. This article outlines the regulations, compares them to those originally proposed in May 1990, presents a compliance timeline, and touches upon Society concerns. PMID- 1603593 TI - Season for Salmonella precautions continues. PMID- 1603594 TI - Computer technology, patients, and modern medicine. PMID- 1603595 TI - Computers can ease management functions. PMID- 1603596 TI - Physician-specific outcome data: good or bad medicine? PMID- 1603597 TI - New OSHA rules prompt return to crisis mode. PMID- 1603598 TI - [Improvement in the mother-child health record in pediatric health care]. AB - The recommended program of Child Health Care in Austria needs some additions: The first routine visit should be done between the 3rd and 5th week of life because of the insecurity of the young mother. The orthopedic examination must comprise the ultrasonographic examination of the hip. At 7-9 months of age the urinary screening for neuroblastoma must be incorporated into the existing program. The vaccination against haemophilus influenzae Type B must be added to the existing vaccination recommendations. During school age three additional examinations are recommended at 6, 10 and 15 years respectively. PMID- 1603599 TI - [Ultrasound diagnosis of hip dysplasia--current status and future perspectives]. AB - Hip sonography provides a safe pathoanatomical assessment of a newborn hip joint at the earliest possible moment. Based on this safe diagnosis an adequate biomechanical treatment can be started instantly. The mean age of healing even of originally decentered hip joints is 7.5 months, if earliest sonographic diagnosis and adequate biomechanical treatment are performed correctly. Secondary hip surgery can be reduced to a minimum. Cost-benefit-analysis, too, supports the institution of a general sonographic screening of all newborn hip joints. PMID- 1603600 TI - [The Nutrition Commission of the Austrian Society of Pediatrics. 3. Nutrition of premature infants. Vitamins, electrolytes, trace elements]. PMID- 1603601 TI - [Clinical medicine versus homeopathy]. AB - Due to the advance of alternative medicine a critical synopsis by means of the comparison between scientific medicine (clinical medicine) and homeopathy is warranted. The review of studies carried out according to current scientific criteria revealed--at best--a placebo effect of homeopathy. Until now there is no proven mechanism for the mode of action of homeopathy. Sometimes so-called "alternative medicine" prevents effective curative measures. In spite of the justified criticism concerning the technical over-estimation of classical medicine, scientific research should remain the basis of clinical work. PMID- 1603602 TI - [Value of serum sialic acid determination in children]. AB - In order to find out whether sialic acid (SA) is suitable as a tumor marker this compound was determined in the sera of 48 healthy and of 168 sick children. In healthy children under six months of age lower concentrations of SA were found (x = 41 +/- 5 mg/dl) than in subjects aged six months to 18 years (x = 68 +/- 8 mg/dl). Inflammatory diseases of various etiologies lead to a significant increase in both age groups (x = 93 +/- 28 mg/dl), the same could be observed in subjects up to 14 days after surgery. In children with malignant disorders the concentration of SA was significantly higher (x = 83 +/- 27 mg/dl) than in the healthy subjects, but not higher than in patients with inflammatory diseases. We conclude that SA might play a role in the follow up protocol of patients with malignant tumors. PMID- 1603603 TI - Button sequestrum of the tibia and pheochromocytoma. AB - A 16-year-old boy suffers from headaches. A bilateral adrenal pheochromocytoma is diagnosed and removed. After surgery, the image of bone sequestrum has disappeared. Osseous microthrombi secondary to hemoconcentration are responsible for the image of button sequestrum. PMID- 1603604 TI - Persistence of a single pulmonary vein in a child. AB - Persistence of a single pulmonary vein with normal pulmonary venous return is a rape and unusual radiographic finding. We report such a case with the venous opacity partially visible on the right border of the heart on a plain frontal chest film. MRI showed beautifully the pulmonary vein and can now replace angiocardiography. PMID- 1603605 TI - Oxaprozin: a new NSAID. AB - Oxaprozin, a propionic acid derivative, is a non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its spectrum of anti inflammatory activity has been demonstrated in both in vitro and in vivo models.1 The majority of published clinical trials have focused on the use of oxaprozin (from Searle) in the treatment of osteoarthritis and rheumatoid arthritis. PMID- 1603606 TI - Current concepts regarding the anterior cruciate ligament. AB - In an athlete, the torn anterior cruciate ligament (ACL) is best managed by surgical reconstruction. The failure to recognize an acutely torn ACL and the resulting inappropriate treatment can result in additional irreversible damage to the athlete's knee. Yet, as recently as 1983, a report documented that physicians failed to diagnose acutely torn ACLs in 93% of 103 patients who were subsequently seen with symptomatically unstable knees. Persistent instability is manifested by paroxysmal anterior shifts of the tibia on the femur during pivotal maneuvers, which may cause further irreparable damage. The injury has commonly gone unrecognized despite the fact that knowledge of the ACL's function, mechanism of its injury, and clinical presentation when torn can often lead to a strong suspicion of a torn ACL through history-taking alone. Documentation of hemarthrosis and a poor end point to passive tibial anterior displacement on the femur while the knee is between 10 degrees and 30 degrees of flexion confirms the diagnosis. Arthroscopically aided intra-articular reconstruction has emerged as the favored technique over extra-articular and combined intra-articular/extra articular procedures. The bone-one-third patella tendon-bone autogenous graft remains the standard to which other graft materials are compared in reconstructing the ligament. Allograft reconstruction offers similar results with less postoperative morbidity and is reasonably safe; the spread of human immunodeficiency virus from donor to patient remains a remote possibility. PMID- 1603607 TI - Tobramycin-impregnated cement in total hip replacements. AB - The clinical effect of adding 1.2 g of tobramycin powder to each 40-g pack of powdered polymethylmethacrylate used in hip replacement surgery was investigated. Fifteen patients underwent total hip replacement in which a cemented femoral prosthesis and a cementless acetabular prosthesis were used. Postoperatively, the tobramycin levels in the blood and in the wound drainage fluid were measured. The serum tobramycin concentrations were low, whereas the wound drainage fluid contained highly effective antibacterial concentrations. There was no evidence of reaction or toxicity to the antibiotic-impregnated bone cement. PMID- 1603608 TI - Surgical management of chronic ulnar collateral ligament insufficiency of the thumb metacarpophalangeal joint. AB - We studied 33 patients with "gamekeeper's thumb" who underwent surgical treatment comprising ulnar collateral ligament (UCL) advancement in 14, arthrodesis in 11, reconstruction in 6, and primary repair in 2. Results were satisfactory in 76% of the cases and unsatisfactory in 24%. From our study and review of the literature, we concluded that the best results are obtained after surgical treatment in the acute stage, because results are inconsistent and poorer after treatment of chronic lesions; reconstructive procedures based on the surgical pathology are recommended over UCL advancement and late primary repairs; and arthrodesis is a reliable salvage procedure. PMID- 1603609 TI - Results of conservative treatment for recalcitrant anterior knee pain in active young adults. AB - The purpose of this study was to determine the success rate of a standard rehabilitation protocol in the treatment of recalcitrant anterior knee pain in active young adults. All patients were active military duty personnel. Patients with a diagnosis of recalcitrant anterior knee pain were enrolled in a standard supervised program of physical therapy. Between 1986 and 1989, 139 patients met the criteria for inclusion in the study. The average age was 25.5 years, and the average time in military service was 67 months. There were 123 men and 16 women. The average duration of supervised treatment was 5.3 months. Only 34% (47 patients) were successfully returned to duty. The remainder received medical discharges. Statistically significant factors associated with successful return to full duty included older age (27.4 vs 24.5 years) and longer duration in service (98 vs 51 months). In addition, patients who returned to duty did so after an average of only 3 months of supervised rehabilitation, whereas treatment failures averaged 7.5 months of therapy. PMID- 1603610 TI - Pasteurella infection in a total knee arthroplasty. AB - Hematogenous infection of a total joint arthroplasty is a serious complication that has well-known etiologies. One of the most unusual inciting events is a bite wound. Pasteurella multocida is an anaerobic organism found in the mouths of mammals that has rarely been found to infect total knee arthroplasties. Prompt recognition of such an infection and prophylactic treatment with a penicillinase resistant penicillin should maximize the patient's opportunity to eradicate such an infection. PMID- 1603611 TI - Knee dislocations with intact PCL. AB - Complete knee dislocations are infrequent but serious injuries resulting from a wide spectrum of traumatic events. Significant soft tissue and ligamentous damage usually result. Previous experience and several reports in the literature had led us to believe that complete dislocations were associated with both ACL and PCL rupture. Three cases of documented complete knee dislocation in which the PCL is preserved intact are presented. PMID- 1603612 TI - Tarsal tunnel syndrome secondary to neurilemmoma. AB - Neurilemmoma is an uncommon cause of tarsal tunnel syndrome, and no other cases of this disorder secondary to a lesion at the bifurcation of the medial and lateral plantar nerves have been described. In this case, a 2 x 0.5 x 1-cm mass was palpable on physical examination, and, after failed conservative treatment, surgical excision brought prompt relief of symptoms. PMID- 1603613 TI - Imaging rounds. Synovial chondromatosis. AB - The following case is presented to illustrate the roentgenographic and clinical findings of a condition of interest to the orthopaedic surgeon. Initial history, physical findings, and roentgenograms are found on the first two pages. The following pages present the final clinical and roentgenographic differential diagnosis. PMID- 1603614 TI - Customized plating techniques for juxta-articular fractures and osteotomies. AB - Juxta-articular fractures and osteotomies must be reduced and maintained in satisfactory position to allow for normal joint function at both the involved joint and the adjacent ones. Internal fixation of these fractures is often difficult because of the proximity of the fracture site to the articular cartilage. Modification of currently available bone plates by customization can increase the orthopaedist's armamentarium and allow rigid fixation with early motion. This will help attain early functional recovery and good long-term results. PMID- 1603615 TI - Hereditary spastic paraplegia. AB - Hereditary spastic paraplegia (HSP) is a genetically determined condition that is often confused with, and misdiagnosed as, spastic diplegic cerebral palsy. Both autosomal dominant and recessive forms have been reported. We present three index patients in a single family with this disease. The pedigree of three generations strongly supports the genetic basis of an autosomal dominant condition. Awareness of this entity may help in genetic counseling and possibly avoiding some medical litigation related to cerebral palsy patients. PMID- 1603616 TI - Three traction knots for the orthopaedic surgeon. AB - This article reviews the technique of tying three knots that are used by orthopaedic surgeons when treating a patient in skeletal traction--the traction knot, the bowline, and the cow hitch. The advantages of the bowline and the cow hitch over the traction knot are also discussed. PMID- 1603618 TI - Patient guide. Fractures. PMID- 1603617 TI - The Thurstan-Holland fragment. AB - The Thurstan-Holland fragment, a small triangular piece of metaphyseal bone, may provide the only roentgenographic evidence of a prior epiphyseal separation that subsequently resolved. PMID- 1603619 TI - Endotoxin and hypoxia-induced intestinal necrosis in rats: the role of platelet activating factor. AB - We have previously shown that intravascular platelet activating factor (PAF) causes ischemic bowel necrosis in rats morphologically similar to neonatal necrotizing enterocolitis (NEC). Because endotoxin (LPS) and hypoxia are risk factors for NEC, we studied their effect on PAF metabolism and the development of intestinal injury. Young male Sprague-Dawley rats were anesthetized with pentobarbital and divided into six experimental groups: 1) control, 2) LPS alone (2 mg/kg), 3) hypoxia alone (5% O2), 4) LPS+hypoxia, 5) WEB 2086 (PAF antagonist)+LPS+hypoxia, and 6) SRI 63-441 (PAF antagonist)+LPS+hypoxia. Evaluations included blood pressure recording, superior mesenteric artery blood flow, arterial blood gas, white blood cell count, hematocrit, plasma PAF, plasma acetylhydrolase, plasma tumor necrosis factor, intestinal perfusion, and intestinal injury at 3 h. We found that LPS+hypoxia synergistically contributed to hypotension (mean blood pressure 27 +/- 5.6% baseline versus 101 +/- 3.9% control), metabolic acidosis (pH 7.05, base deficit 24 mEq/L), hemoconcentration, decreased superior mesenteric artery blood flow (2.2 +/- 0.3 mL/min versus 5.8 +/ 0.2 mL/min control), and intestinal injury. The morbidities resulting from LPS+hypoxia were partially or completely prevented by PAF antagonists. In addition, animals treated with LPS+hypoxia had neutropenia, elevated plasma acetylhydrolase, and elevated plasma TNF. These results suggest that endogenous PAF may contribute to LPS+hypoxia-induced intestinal hypoperfusion and necrosis. PMID- 1603620 TI - The effect of hyperoxic exposure on antioxidant enzyme activities of alveolar type II cells in neonatal and adult rats. AB - Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate. PMID- 1603621 TI - Short-term distribution kinetics of intratracheally administered exogenous lung surfactant. AB - The short-term distribution kinetics of exogenous surfactant distribution after intratracheal instillation was investigated in surfactant-deficient neonatal piglets during assisted conventional mechanical ventilation and by high-frequency jet ventilation using exogenous calf lung surfactant extract (CLSE) labeled with 99mTc. Surfactant deficiency was induced by repeated bronchoalveolar lavage in piglets (1.2 +/- 0.4 kg, 1.4 +/- 0.7 d of age), and the short-term distribution kinetics of instilled, labeled CLSE were followed by gamma radioscintigraphy. Animals ventilated by either conventional mechanical ventilation or high frequency jet ventilation showed similar improvement in arterial/alveolar oxygen ratios after surfactant replacement therapy (0.47 +/- 0.03 prelavage, 0.09 +/- 0.01 postlavage, 0.36 +/- 0.06 postsurfactant). This correlated directly with dynamic radioscintigraphic results showing that instilled CLSE began to distribute to the lungs within 5 s, and was present in substantial amounts in standardized symmetrical lung fields (central, right, and left; upper and lower) within 20 s of tracheal instillation. Subsequent measurements over 30 min showed continued presence of radiolabeled CLSE in all five areas of the lung, with no significant difference between conventional mechanical ventilation and high frequency jet ventilation animals. Static (5-min) analyses at the end of this period showed that surfactant had distributed relatively symmetrically with 30% of the CLSE located in central regions, 40% in the upper lobes, and 30% in the lower lobes. In contrast, piglets receiving 99mTc in saline showed nonuniform distribution with multiple filling defects noted throughout the lungs. The rapid kinetics and ventilation independence of CLSE distribution suggest that surfactant spreading phenomena after tracheal instillation may facilitate the delivery of exogenous surfactant into aerated lungs in therapeutic applications. PMID- 1603622 TI - Adenosine triphosphate and adenosine increase the pulmonary blood flow to postnatal levels in fetal lambs. AB - We investigated the hypothesis that purine nucleotides may mediate the pulmonary vasodilation that occurs at birth in fetal lambs. We studied nine fetal lambs 3 d after placement of intravascular catheters, a flow transducer around the left pulmonary artery, and an inflatable vascular occluder around the ductus arteriosus. The pressure-flow relationship of left lung during a brief occlusion of the ductus arteriosus was studied as an index of pulmonary vascular resistance. We investigated the pulmonary vascular effects of adenosine, ATP, or saline (control) in doses of 0.01-2.50 mumol/kg/min infused into the right atrial line, and measured blood adenosine and ATP levels in samples from the pulmonary artery and left atrium. We also investigated the mechanism of pulmonary vascular effects of adenosine and ATP. Adenosine and ATP caused significant decreases in pulmonary vascular resistance and increases in pulmonary blood flow in doses of 0.08-2.5 mumol/kg/min. The pulmonary blood flow increased to levels seen in postnatal lambs at doses of 1.2 and 2.5 mumol/kg/min of adenosine and ATP. The baseline blood adenosine and ATP levels in fetus were 8 and 70% of levels in postnatal lambs. ATP concentrations increased to postnatal levels and adenosine levels increased to 20% of postnatal levels at infusion rates of 1.2 and 2.5 mumol/kg/min. The pulmonary vasodilation caused by adenosine and ATP was attenuated by 8-phenyltheophylline and cibacron blue, respectively, but not by indomethacin. We conclude that adenosine and ATP are pulmonary vasodilators and increase the fetal pulmonary flow to postnatal levels in doses that increase their blood concentrations to less than or equal to postnatal levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603623 TI - Age-related changes in pulmonary venous epinephrine concentration, and pulmonary vascular response after intratracheal epinephrine. AB - Using an isolated salt-perfused lung model in rabbits from 1 to 21 d of age, we measured the concentration of epinephrine in the pulmonary venous drainage and the pulmonary vascular response after a single dose of intratracheal epinephrine (0.1 microgram/g body weight). Lungs from 30 rabbits were isolated, ventilated, and perfused at one of four age groups (n = 7-8 per group). After ventilation/perfusion was judged to be stable, saline control was injected into the trachea, changes in pulmonary pressure were recorded, and perfusate was collected for 45 s. After restabilization, epinephrine was injected into the trachea, changes in pulmonary vascular pressure were recorded, and perfusate was collected for 45 s x two aliquots. Perfusate epinephrine concentrations were determined by HPLC. Little epinephrine was detected in the perfusate after control over all age groups, and little vascular response was noted. There was a significant age-related increase in perfusate epinephrine concentration as well as an age-related increase in vascular response (increased PAP), with the maximum epinephrine concentration and change in PAP noted at 14-21 d [group 4 = (1.72 +/- 0.42) x 10(4) pmol/L]. Also, in rabbits less than 6 d of age, deposition of epinephrine into the pulmonary venous drainage was delayed. In the rabbit model, the concentration of epinephrine reaching the heart via pulmonary circulation after intratracheal injection is, at birth, very low, and the pulmonary vascular response is diminished. Both increase as a function of age until 14-21 d of age. These findings may have clinical importance in human neonatal resuscitation endeavors. PMID- 1603624 TI - Relationship between cardiac cycle length and ventricular relaxation rate in the chick embryo. AB - We hypothesized that during chick embryo cardiac development, cycle length decrease (heart rate increase) may be associated with developmental changes in the ventricular relaxation rate constant, tau, which can be estimated from ventricular pressure decrease by the function P(t) = P0e-t/tau, where P0 = pressure at the time of minimum time derivative of ventricular pressure and t = time. Natural logarithm conversion results in a linear relation between In P(t) and t with slope of -1/tau. We determined tau in Hamburger-Hamilton stage 17-27 (d 3-5) embryos (n = 35) at intrinsic cycle length and in stage 24 embryos (n = 5) during cardiac cycle length perturbations with the hot-cold probe technique. Regression analysis of In P(t) from the minimum dP/dt until t = 30 ms was used to estimate tau. Intrinsic cycle length decreased during development from stage 17 to 27 and tau decreased linearly as cycle length decreased (r = 0.39, p less than 0.005). Thus, during early development, both tau and cycle length decrease (relaxation rate and heart rate increase). In stage 24 embryos, cycle length perturbation yielded a nonlinear cycle length-dependent relation with tau, with a plateau at cycle lengths less than intrinsic, i.e. tau decreased with cycle length decrease to intrinsic cycle length, then tau plateaued with further cycle length decrease. These findings demonstrate that ventricular relaxation rate is both maturation and cycle length dependent. The plateau effect of the tau-cycle length relationship may be due to developmental limitations of the calcium transport system. PMID- 1603625 TI - Cerebral histologic and electrocorticographic changes after asphyxia in fetal sheep. AB - Asphyxia can cause neurologic damage in the fetus, but there are few data relating severity or duration of asphyxia to the degree of cerebral damage. We report cerebral histologic and electrophysiologic changes after asphyxia in chronically instrumented late-gestation fetal sheep. We reduced uterine blood flow to produce an ascending aortic blood oxygen content less than 1.5 mM for either 30 or 60 min (n = 13). In a subsequent protocol (n = 6), if full occlusion of the common uterine artery for 15 min did not reduce the EEG voltage to less than 20% of baseline, supplementary maternal hypoxia was added for a maximum of 120 min. Histologic outcome was assessed 3 d postinsult. Uterine artery occlusion resulted in severe hypoxemia, hypercarbia, acidosis, and an initial hypertension and bradycardia. Eight of 14 surviving fetuses showed neuronal damage, with greatest loss in the parasagittal cortex, striatum, and the CA1/2 region of the hippocampus. Neuronal damage was strongly associated with the percentage of decrease in blood pressure during the insult (r = 0.75, p less than 0.005) but not with the degree of hypoxia. No other factor was independently predictive, but, when considered separately, pH (r = 0.54; p less than 0.05) and loss of intensity of the EEG (r = 0.61, p less than 0.02) at the end of asphyxia were also correlated with outcome. The pH fell to less than 7.0 in six of eight fetuses with damage, whereas it remained greater than 7.0 in five of six without damage (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603626 TI - Fetal alcohol syndrome and fatty acid ethyl esters. AB - Fetal alcohol syndrome is the leading known cause of mental retardation. The syndrome, defined as growth retardation, midface hypoplasia, and neurologic dysfunction, represents only part of the spectrum of fetal alcohol effects. The biochemical mechanism of teratogenesis is unknown. In adults, metabolites of ethanol, FAEE, are known to accumulate in major organs. The formation of FAEE is catalyzed by a family of enzymes, FAEE synthases. Our hypothesis is that accumulation of FAEE in the embryo results in fetal alcohol syndrome. We have developed assays for FAEE and FAEE synthase activity using mg of tissue. Using these assays, we have shown the following: Human placenta, mouse placenta, heart, and liver are active in catalyzing the formation of FAEE. One h after maternal ethanol administration on gestational d 14, mouse placenta and fetuses accumulated significant quantities of FAEE. The fatty acid incorporated into FAEE was tissue dependent. Tissues from pregnant animals given ethanol on gestational d 7 showed persistence of FAEE on gestational d 14. We conclude that: 1) human and mouse placentas have significant FAEE synthase activity, 2) mouse heart, liver, placenta, and fetal tissues accumulate significant amounts of FAEE after maternal ethanol exposure, 3) there is tissue specificity for the fatty acid incorporated into FAEE, and 4) FAEE may persist for 7 d in placentas. These results provide a basis for further research into the role of FAEE in the development of fetal alcohol syndrome. PMID- 1603627 TI - Enzyme augmentation in moderate to life-threatening Gaucher disease. AB - Gaucher disease type 1 (GD type 1) is the most prevalent lysosomal storage disease and has its highest frequency in the Ashkenazi Jewish population. Deficiency of the enzyme, acid beta-glucosidase, results in the deposition of glucocerebroside primarily in macrophages. The accumulation of such "Gaucher cells" leads to visceromegaly, hepatic and bone marrow dysfunction, hypersplenism, and bony disease. Eleven GD type 1 patients, ages 4-52 y, with moderate to life-threatening manifestations, received 6-12 mo of enzyme augmentation with a macrophage-targeted acid beta-glucosidase preparation. Within 6 mo, substantial increases in Hb levels (mean = +30%) and platelet counts (mean = +39%) were observed. Hepatic and splenic volumes decreased by approximately 20% (range = 3-35%) and approximately 35% (20-52%), respectively. Hematologic and hepatic volume improvements were similar in the splenectomized (n = 4) and nonsplenectomized (n = 7) patient groups. In this patient population, no major differences were observed in the hematologic and visceral improvements with enzyme doses of 30, 50, or 60 IU/kg administered every 2 wk. Normal levels of acid beta-glucosidase activity were present in hepatic autopsy samples from one patient 11 d after enzyme infusion. In comparison, exogenous activity was absent from brain and lung specimens of the same patient. High levels (approximately 10 fold normal) were present in bone marrow samples from two patients obtained at 1 and 11 d after infusions. These studies demonstrate biochemical and clinical improvements by targeted enzyme augmentation in GD type 1, even in far advanced, life-threatening involvement.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603628 TI - Allogenic bone marrow transplantation in severe Gaucher disease. AB - Gaucher disease is the most prevalent lysosomal storage disease. This autosomal recessive disease is caused by the defective activity of the enzyme acid beta glucosidase and the resultant accumulation of glucosylceramide primarily within cells of the reticuloendothelial system. Because the primary manifestations of Gaucher disease are due to involvement of monocyte/macrophage-derived cells, this disease is thought to be an excellent candidate for curative intervention via bone marrow transplantation (BMT). A Hispanic female with subacute neuronopathic Gaucher disease and rapidly progressing visceral manifestations underwent BMT at 23 mo of age using her histocompatible normal brother as the donor. Cytogenetic analyses demonstrated complete, stable engraftment by 1 mo post-BMT. During the subsequent 24 mo, clinical, biochemical, enzymatic, and histologic studies demonstrated nearly complete correction in the viscera. Her neuropathic manifestations did not progress. Complete reconstitution of enzymatic activity in peripheral blood leukocytes was achieved by 1 mo. Cytogenetic analyses demonstrated complete engraftment by d 79 and nearly complete loss of bone marrow Gaucher cells was observed by 8 mo. Plasma glucosylceramide levels normalized by 8-12 mo. Nearly coincident improvements in hepatic size, enzyme levels, and histology were found by 12-24 mo post-BMT. Fatal sepsis occurred at 24 mo post BMT. Autopsy revealed sparse Gaucher cells in clusters in the liver, lymph nodes, and lungs as well as the lack of periadventitial Gaucher cells surrounding brain vessels. The findings provide the time course and rationale for studies directed to gene therapy via BMT for this disease after introduction of acid beta glucosidase gene constructs into autologous pluripotent stem cells of selected Gaucher disease patients. PMID- 1603629 TI - Abnormal galactosylation of complex carbohydrates in cultured fibroblasts from patients with galactose-1-phosphate uridyltransferase deficiency. AB - An abnormality in galactosylation of complex carbohydrates may be important in the pathogenesis of the long-term complications of classic (galactose-1-phosphate uridyltransferase-deficient) galactosemia. The ability of nine galactosemic fibroblast preparations to be galactosylated with a purified galactosyltransferase was measured as an indicator of vacant sites where galactose would normally reside. The amount of galactose transferred to cell protein from galactosemic patients was significantly higher than that transferred to a group of seven controls (p less than 0.005). Galactosyltransferase activity of the galactosemic cell preparation toward N-acetylglucosamine was also significantly higher than normal (p less than 0.01), and there was a linear relationship between these two parameters in galactosemic but not normal cells. These findings suggest that there is defective galactosylation of galactosemic cell complex carbohydrates and that such cells increase their galactosyltransferase levels in an attempt to compensate for the defect. Defective galactosylation may be implicated as an etiologic factor in complications observed in galactosemic patients even when treated with galactose restricted diets. PMID- 1603630 TI - Regional activity of galactose-1-phosphate uridyltransferase in rat brain. AB - The sp act of galactose-1-phosphate uridyltransferase has been measured in individual regions of adult rat brain to see if site-specific differences in enzyme activity can aid in the understanding of brain abnormalities observed in well-treated galactosemic patients. The sp act in the cerebellum, brain stem, and midbrain were higher than in the cortex, hippocampus, and striatum. Activity in the cerebellum was 2-fold greater than that found in the cortex. Steady state levels of mRNA of the enzyme in the cerebellum were twice that of the cortex corresponding to the ratio of enzyme sp act in the two regions. Measurement of the kinetic parameters in tissue from the cerebellum and cortex revealed that the regional specificity in enzyme activity observed in the brain represents differences in the Vmax. Inhibition of the enzyme by uridine and uridine triphosphate was essentially the same for all regions and was not influenced by the 2-fold differences observed in the levels of enzyme. Inhibition by uridine was significantly greater than that for uridine triphosphate. PMID- 1603631 TI - Genetic heterogeneity in patients with X-linked recessive chronic granulomatous disease. AB - Genetic heterogeneity in 12 patients from 11 different families with X-linked recessive chronic granulomatous disease was studied by Southern blot analysis using cytochrome b heavy-chain cDNA as a probe. We found the abnormal restriction length fragment patterns of the cytochrome b heavy-chain gene in three families, which were not observed in healthy controls. DNA from one patient showed the abnormal patterns after digestion with several restriction enzymes. The DNA of two other patients showed the abnormality only with TaqI and PstI. Analysis of the same family members indicated that these abnormal patterns cosegregated with the disease. The other nine patients from eight families did not have any abnormalities detectable by Southern blot analysis. Although further experimentation should be done to study the molecular genetic heterogeneity in most X-linked chronic granulomatous disease families (eight of 11), we were able to demonstrate at least three different types of mutations in the cytochrome b heavy-chain gene responsible for the disease. PMID- 1603632 TI - The nutritional regulation of circulating placental lactogen in fetal sheep. AB - Maternal and fetal plasma ovine placental lactogen (oPL), insulin, and IGF-I levels were measured in response to the starvation and refeeding of pregnant sheep on two defined planes of nutrition. Chronically catheterized pregnant ewes were placed on either a high plane (n = 5) or low plane (n = 5) of nutrition at least 1 wk before the experiment. At 125 to 135 d gestation, the ewes were starved for 72 h and then an i.v. infusion of 10% glucose was administered over 4 h, followed by refeeding at the designated nutritional plane. Plasma oPL levels of fetuses whose mothers had been on a high plane of nutrition were significantly higher during starvation (p less than 0.05) than those of fetuses whose mothers had been on a low plane (high + 0.54 +/- 0.17 and low -0.02 +/- 0.17 nmol/L from mean control levels). Intravenous glucose infusion to the ewes at the end of starvation caused a marked rise in fetal plasma oPL levels in both groups (increments of 2.61 +/- 1.4 nmol/L in the high group and 2.81 +/- 1.16 nmol/L in the low group). Maternal oPL levels did not differ significantly between the two nutritional groups during starvation and did not change during glucose infusion. Fetal and maternal plasma IGF-I levels both fell during starvation. Maternal IGF I levels fell faster in the high group (-17.9 +/- 4.5 at 24 h versus -4.7 +/- 7.2 nmol/L in the low group), but the groups were not different at the end of starvation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603633 TI - Bioavailability in man of iron in human milk and cow's milk in relation to their calcium contents. AB - Iron absorption from human milk and cow's milk was compared in the same subjects using two radio-iron tracers and extrinsic labeling of the iron. Previously observed higher iron absorption from human milk was confirmed as 19.5 +/- 17.3% (mean +/- SD) in cow's milk versus 48.0 +/- 25.5% in human milk; mean individual absorption ratio was 0.39 +/- 0.18 (p less than 0.0001). Cow's milk has a several times higher content of calcium, recently established to be a potent inhibitor of iron absorption. Adding calcium chloride to human milk in amounts to equate the calcium content of cow's milk significantly reduced iron absorption [39.1 +/- 17.8% (mean +/- SD) versus 21.3 +/- 10.6%]; mean individual absorption ratio with or without added calcium was 0.58 +/- 0.12 (mean +/- SD) (p less than 0.0001). Differences in calcium content could explain at least 70% of the difference in iron bioavailability between milks. It is suggested that the remaining 30% difference may mainly be an artifact related to inhomogeneous radioiron-labeling of milk iron compounds, especially in human milk, and that the main difference in true iron absorption between human and cow's milk is related to their different calcium contents. The rather high fractional iron absorption from human milk can be explained by its low iron content. There is nothing to indicate that human milk contains any enhancer of iron absorption. The marked inhibiting effect of calcium on iron absorption should be considered in the design of infant formulas to achieve an optimal balance in the contents of calcium and iron. PMID- 1603634 TI - Growth hormone secretory capacity of individual somatotropes in rats with chronic renal insufficiency. AB - Growth failure is a common consequence of chronic renal insufficiency (CRI) in children and may be due to a number of factors. With regard to growth hormone (GH), regulation is often abnormal in CRI patients. The present study investigated the effect of CRI on the GH secretory responsiveness to GH-releasing hormone in individual rat pituitary somatotropes. Male Sprague-Dawley rats underwent a 5/6 nephrectomy to produce CRI. Control rats (SHAM) received sham operations, which included kidney decapsulation but not removal. Two wk later, during a period of stable uremia, serum creatinine [CRI: 1.1 +/- 0.08 mg/dL (97 +/- 7 mumol/L); SHAM: 0.4 +/- 0.04 mg/dL (35 +/- 4 mumol/L)] and serum urea nitrogen [CRI: 60.7 +/- 8.3 mg/dL (21.7 +/- 3.0 mmol/L); SHAM: 15.8 +/- 1.2 mg/dL (5.6 +/- 0.4 mmol/L)] were significantly elevated in the CRI rats (p less than 0.0005). Weight gain (p less than 0.0005), length gain (p less than 0.0005), food intake (p less than 0.0005), and food efficiency (p less than 0.005) were all significantly lower in the CRI rats. The GH secretory capacity of individual somatotropes was determined using the reverse hemolytic plaque assay technique. Plaque areas were measured to assess relative amounts of GH secreted. The total number of pituitary cells per rat, the percentage of somatotropes, and the mean plaque areas were similar for the two groups. These findings compare favorably with our in vitro study of GH responsiveness in perifused rat pituitary cells under conditions of mild uremia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603635 TI - Prevalence of human growth hormone-1 gene deletions among patients with isolated growth hormone deficiency from different populations. AB - Familial isolated growth hormone deficiency type IA results from homozygosity for either a 6.7-kb or a 7.6-kb hGH-1 gene deletion. Genomic DNA was extracted from circulating lymphocytes of 78 subjects with severe isolated growth hormone deficiency (height less than -4.5 SD score) and studied by polymerase chain amplification and by restriction endonuclease analysis looking for gene deletions within the hGH-gene cluster. The individuals analyzed were broadly grouped into three different populations (North-European, n = 32; Mediterranean, n = 22; and Turkish, n = 24). Ten out of 78 patients studied presented with an hGH-1 gene deletion; eight out of these 10 showed a 6.7-kb gene deletion, the remaining two a 7.6-kb hGH-1 gene deletion. Five of the 10 subjects developed anti-hGH antibodies to hGH replacement followed by a stunted growth response. Family studies of the affected patients were performed, revealing consanguinity in all the families, and the corresponding heterozygosity for the deletion was present in each of the parents. The results of our study revealed a prevalence for an hGH 1 gene deletion in three out of 32 North-European, three out of 22 Mediterranean, and four out of 24 Turkish patients with growth hormone deficiency (height less than 4.5 SD score). These data are important for prenatal diagnosis of at-risk pregnancies and for families at risk for recurrence and underline clearly the fact that the hGH-I gene deletion represents a common cause for growth hormone deficiency associated with severe growth retardation (height less than -4.5 SD score). PMID- 1603636 TI - Comparison between spontaneous gonadotropin concentration profiles and gonadotropin response to low-dose gonadotropin-releasing hormone in prepubertal and early pubertal boys and patients with hypogonadotropic hypogonadism: assessment by using ultrasensitive, time-resolved immunofluorometric assay. AB - To assess whether nocturnal gonadotropin concentration profiles in children could be predicted by measurement of peak gonadotropin levels after gonadotropin releasing hormone (GnRH) administration, we measured spontaneous gonadotropin levels every 20 min and the gonadotropin responses to low-dose GnRH using an ultrasensitive, time-resolved immunofluorometric assay in 61 boys with short stature and/or delayed puberty. Spontaneous nocturnal LH pulses were observed in 58 out of 61 patients. After GnRH administration in a dose of 25 ng/kg, all of the 61 patients had significant LH and FSH responses, and GnRH-stimulated peak LH and FSH levels were highly correlated with maximal spontaneous nocturnal LH and FSH levels, respectively (r = 0.83 for LH and r = 0.91 for FSH; p less than 0.00001). Analysis of individual subjects revealed that GnRH-stimulated peak LH levels were almost identical to maximal nocturnal LH levels in the subjects whose GnRH-stimulated peak LH levels were between 5 and 10 IU/L, whereas GnRH stimulated peak LH levels tended to be higher than maximal nocturnal levels in the subjects whose GnRH-stimulated peak LH levels were 5 IU/L or lower. To determine if there were any parameters in the gonadotropin response to GnRH that might be useful in distinguishing early pubertal boys from prepubertal boys, we evaluated the gonadotropin response to GnRH in 44 prepubertal and 10 early pubertal normal short boys. Although maximal nocturnal LH levels did not overlap between prepubertal and pubertal groups, GnRH-stimulated LH peak levels overlapped considerably between the two groups. Even the GnRH-stimulated peak LH to peak FSH ratio overlapped between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603638 TI - Saul Krugman Festschrift. PMID- 1603637 TI - Perinatal human immunodeficiency virus infection: ruminations on mechanisms of transmission and methods of intervention. AB - Perinatal human immunodeficiency virus (HIV) infection is undoubtedly a multifactorial process. Neither the quantity of viremia nor the level of neutralizing antibody in the infected mother is alone predictive of HIV transmission to her offspring. Additional cofactors may include the ability of maternal immunity to control the host cell range and rate of viral replication. The placenta probably constitutes an effective barrier to viral transmission unless disrupted by processes such as syphilis. Prevention of such breaks in the trophoblast barrier and efforts to stimulate maternal and newborn HIV-specific immunity may further decrease the perinatal transmission rate. PMID- 1603639 TI - Serious respiratory tract disease caused by respiratory syncytial virus: prospects for improved therapy and effective immunization. PMID- 1603640 TI - Past, present, and future of measles, mumps, and rubella virus vaccines. PMID- 1603641 TI - The battered child at thirty: what can be learned from Saul Krugman at eighty? PMID- 1603642 TI - Sexual abuse and corporal punishment during childhood: a pilot retrospective survey of university students in Costa Rica. AB - A sample of 497 students at the University of Costa Rica completed a survey on perceptions and experiences with various forms of punishment and experiences with sexual abuse during childhood. Spanking was shown to be the most widely accepted and most common form of discipline. The majority of the students considered most types of punishment forms of abuse. This study lacks a comparison group and cannot be generalized to the entire Costa Rican population. The section on sexual abuse demonstrated that 32% of the women and 13% of the men experienced some type of sexual abuse during childhood. The abuse mainly occurred between the ages of 5 and 10, and men were most often perpetrators. PMID- 1603643 TI - The introduction of human immunodeficiency virus into the North Carolina pediatric population. AB - The authors reviewed the means by which human immunodeficiency virus (HIV) seropositivity was acquired for the 134 seropositive children seen at Duke University Medical Center prior to September 1990. Perinatal transmission occurred in 111 (83%) and blood product transmission in 15 (11%). Of the 108 mothers (there were three sets of siblings) responsible for perinatal transmission, 44 (41%) had acquired their infection while residing in North Carolina. Intravenous (IV) drug use by the mother or her sexual partner was the significant risk factor for maternal infection in 91 (84%) of the total cases and in 38 (86%) of the 44 women infected in North Carolina. The proportion of women who acquired their HIV infection from a sexual partner who was an IV drug user was significantly greater for mothers who were resident in North Carolina when infected compared with mothers infected elsewhere (P less than .001). On the basis of admission to drug treatment programs during the 1990 fiscal year, cocaine is the predominant IV drug used in North Carolina. Admissions to cocaine abuse programs occurred throughout the state, and mothers who acquired HIV infection from IV drug use were more likely to live in counties with a higher frequency of cocaine abuse treatment. PMID- 1603644 TI - Absence of compensation and reasoning-like processes in the perception of orientation in depth. AB - When errors are present in the perceived depth between the parts of a physically stationary object, the object appears to rotate as the head is moved laterally (Gogel, 1980). This illusory rotation has been attributed either to compensation (Wallach, 1985, 1987) or to inferential-like processes (Rock, 1983). Alternatively, the perceived distances of and directions to the parts of the object are sufficient to explain the illusory perceived orientations and perceived rotations of the stimulus. This was examined in three experiments. In Experiment 1, a perceived illusory orientation of a stimulus object extended in depth was produced by misleading binocular disparity and was measured at two different lateral positions of the head under two conditions. In the static condition, the head was stationary at different times at each of the two measurement positions of the head. In the dynamic condition, continuous motion of the head occurred between these two positions. In Experiment 2, static and dynamic conditions of illusory stimulus orientation were observed with the head stationary. In Experiment 3, a perspective illusion instead of binocular disparity produced the errors in perceived depth. In no experiment did the perceived orientation of the object differ for the static and dynamic conditions. In the absence of head motion, neither compensatory nor inferential-like processes were available. It is concluded that these processes are not needed to explain either illusory or nonillusory perceptions of the orientation or rotation of stimuli viewed with a laterally moving head. PMID- 1603645 TI - A generalized visual latency explanation of the Pulfrich phenomenon. AB - The classical visual latency explanation of the Pulfrich phenomenon is generalized to allow for the possibility that the visual system uses velocity information from motion detectors to compensate for spatial lag due to time lag, in identifying the instantaneous position of a moving object. The results of the reported experiment verify one consequence of the generalized version: the elliptical apparent path is skewed away from the filtered eye. The results suggest also that the extrapolation factor increases with visual latency and that there is a different extrapolation factor for each eye when the eyes are illuminated unequally. PMID- 1603646 TI - Amplitude rise time and the perception of the voiceless affricate/fricative distinction. AB - Variation of amplitude envelope at stimulus onset has been considered to be of primary importance for distinguishing voiceless affricates from fricatives (e.g., [symbol: see text]). In earlier perceptual experiments, however, variation in amplitude rise time was confounded with variation in frication duration. In two experiments, these variables were independently manipulated, and their individual and combined effects for perception of magnitude of [symbol: see text] were examined. Variation in amplitude rise time alone was not sufficient to signal the voiceless affricate/fricative contrast in these experiments, but variation in frication duration alone was sufficient. PMID- 1603647 TI - Filtering versus parallel processing in RSVP tasks. AB - An experiment of McLean, D. E. Broadbent, and M. H. P. Broadbent (1983) using rapid serial visual presentation (RSVP) was replicated. A series of letters in one of 5 colors was presented, and the subject was asked to identify the letter that appeared in a designated color. There were several innovations in our procedure, the most important of which was the use of a response menu. After each trial, the subject was presented with 7 candidate letters from which to choose his/her response. In three experimental conditions, the target, the letter following the target, and all letters other than the target were, respectively, eliminated from the menu. In other conditions, the stimulus list was manipulated by repeating items in the series, repeating the color of successive items, or even eliminating the target color. By means of these manipulations, we were able to determine more precisely the information that subjects had obtained from the presentation of the stimulus series. Although we replicated the results of McLean et al. (1983), the more extensive information that our procedure produced was incompatible with the serial filter model that McLean et al. had used to describe their data. Overall, our results were more compatible with a parallel-processing account. Furthermore, intrusion errors are apparently not only a perceptual phenomenon but a memory problem as well. PMID- 1603648 TI - The role of instructions and familiar size in absolute judgments of size and distance. AB - The effects of familiar size and instructions (apparent, objective) on direct reports of size and distance were evaluated. Subjects estimated the size and distance of two different-sized playing cards or two unfamiliar stimuli under either apparent or objective instructions. The stimuli were presented successively at a distance of 5.48 m under reduced-cue conditions. The form of the instructions selectively influenced the effect of familiar size on absolute judgments of size and distance, with apparent instructions minimizing, and objective instructions promoting, familiar-size effects. The ratio of the distance judgments of the first to the second presented stimuli approximated the relative retinal sizes of the two objects under both apparent and objective instructions, while the ratio of size judgments tended to be either influenced by or independent of the object's relative retinal sizes under apparent and objective instructions, respectively. These results are consistent with Gogel's theory of off-size perception and, in particular, with the claim that, in comparison with apparent instructions, objective instructions are more likely to direct observers to base their judgments on cognitive, as opposed to perceptual, sources of spatial information. PMID- 1603649 TI - Audiovisual integration in perception of real words. AB - Three experiments follow up on Easton and Basala's (1982) report that the "McGurk effect" (an influence of a visibly mouthed utterance on a dubbed acoustic one) does not occur when utterances are real words rather than nonsense syllables. In contrast, with real-word stimuli, Easton and Basala report a strong reverse effect whereby a dubbed soundtrack strongly affects identification of lipread words. In Experiment 1, we showed that a strong McGurk effect does obtain when dubbed real words are discrepant with observed words in consonantal place of articulation. A second experiment obtained only a weak reverse effect of dubbed words on judgments of lipread words. A final experiment was designed to provide a sensitive test of effects of lipread words on judgments of heard words and of heard words on judgments of lipread words. The findings reinforced those of the first two experiments that both effects occur, but, with place-of-articulation information discrepant across the modalities, the McGurk effect is strong and the reverse effect weak. PMID- 1603650 TI - Single-parameter power law psychophysics of auditory numerosity and the psychological moment hypothesis. AB - In the present study, numerosity estimation was investigated. A two-parameter Stevens power law analysis was performed on a total of 944 subjects in six experiments. Two pulse ranges (2-17 or 17-253 pulses) and six pulse rates (either constant or randomly varied within trial blocks) were used, variously, in an unsuccessful attempt to find evidence for a psychological moment, under the supposition that the exponent (or, possibly, the measure constant) would become smaller as increasing numbers of pulses fell within the interval determined by each psychological moment. A single-parameter reanalysis of these six experiments under the initial value condition that a (standard) stimulus of one pulse be assigned a theoretical response (modulus) of one yielded single-parameter equations whose exponents were reliably less varied than those for conventional two-parameter equations in Experiments 1-4 (with randomly varying pulse rates from trial to trial) but not less varied in Experiments 5 and 6 (in which pulse rates were constant within trial blocks). It was concluded that the variable pulse rate condition, with its reduced exponent variability and presumed reduced temporal confounding, provides a more valid estimate of the single-parameter power law exponent for numerosity, which was found to be 0.80. PMID- 1603651 TI - A table of d' for M-alternative odd-man-out forced-choice procedures. AB - There is a class of multiple-alternative forced-choice psychophysical procedures in which the subject is required to identify which one of a number of stimuli differs from the remaining stimuli, without having to consider the direction or sign of the difference. A table giving values of the discrimination index d' as a function of the proportion of correct responses in such odd-man-out procedures was generated by numerical simulation. The table covers experiments with 3 to 32 alternative stimuli. PMID- 1603652 TI - The detection of surface curvatures defined by optical motion. AB - The detectability of surface curvatures defined by optical motion was evaluated in three experiments. Observers accurately detected very small amounts of curvature in a direction perpendicular to the direction of rotation, but they were less sensitive to curvatures along the direction of rotation. Variations in either the number of points (between 91 and 9) or the number of views (from 15 to 2) had little or no effect on discrimination accuracy. The results of this study demonstrate impressive visual sensitivity to surface curvature. Several characteristics of this sensitivity to curvature are inconsistent with many computational models for deriving three-dimensional structure from motion. PMID- 1603654 TI - Another look at attentive fields: comments on Pollack and Jaeger. PMID- 1603653 TI - Three-space inference from two-space stimulation. AB - Oblique contours sloping at 30 degrees with respect to the horizontal were presented alone, in combination to form chevrons, or with a vertical line to form arrowhead or Y patterns; they were projected onto a screen in the frontal parallel plane and viewed from positions that gave viewing angles of 90 degrees (normal to the screen's surface), 53 degrees, or 34 degrees. The perceived orientation of the contours, as assessed by a movable arm that the subjects set to be parallel to the obliques, changed monotonically as a function of viewing angle. The change was as great for single obliques as for combinations of obliques within the chevron, arrowhead, and Y patterns. The results of Experiment 1 were extended in Experiment 2, in which obliques at 30 degrees and 50 degrees with respect to the horizontal were presented singly or in combination as chevron patterns. It is argued that the results of both experiments indicate that single two-space oblique lines are immediately interpreted as lying in three-space and that the changes in perceived orientation are a consequence of this perceptual inference. PMID- 1603655 TI - Society of Certified Clinical Specialists in Psychiatric Nursing to create the NJ Center for Psychiatric Nursing. PMID- 1603656 TI - Preparing future nurses to function in a maternity setting. PMID- 1603657 TI - Review teams for continuing education. PMID- 1603658 TI - Cost of treating HIV may surpass $10 billion by 1994. PMID- 1603660 TI - A day in the life of a school nurse. PMID- 1603659 TI - Development of substance abuse policies in health care settings. PMID- 1603661 TI - [Abuse and violence--what can physicians do?]. PMID- 1603662 TI - [Crisis center--a safe hiding-place]. PMID- 1603663 TI - [The reality behind the bruises--clinical picture and documentation in abuse of women]. AB - Most battered women consult for their injuries at the community health centre or the emergency room--often without disclosing the fact that they are the victims of battery. Beyond venturing to inquire, lending a sympathetic ear and being supportive, with a view to any future criminal proceedings it is particularly important that the attending physician meticulously documents all injuries manifested by a battered woman--even if at that juncture she does not intend to bring charges. If necessary the forensic pathologist can assist the clinician in drawing up a report of the injuries and in assessing their origin. PMID- 1603664 TI - [Legal protection for abused Finnish women]. AB - Many women with injuries resulting from criminal assault are examined by physicians at community health centres in Finland, without any differentiation being made between such injuries and injuries and trauma in general. Most of the victims do not seek medical treatment, and only a few of the 5,000 patients examined annually at forensic medicine departments are related to assault or incest. This suggests that the victims are usually cared for in some other way without a report being made to the police or contact with a physician. PMID- 1603665 TI - [Physician's role in the assessment of criminal assault]. AB - In cases of criminal assault, the medical report should be exhaustive and detailed enough to provide the basis for classification by legal authorities. However, the examining physician should make it explicitly clear to the victim that the examination is entirely voluntary. The Council of Medical Jurisprudence, the highest medicolegal authority, provides public authorities with scientific forensic expertise in cases involving individual legal rights. PMID- 1603666 TI - [Psychological sequelae of rape--can they be reduced?]. PMID- 1603667 TI - [Society must denounce violence against women]. AB - In Iceland there is no established procedure for the care of adult victims of criminal assault (mainly women). There is no statutory obligation to make a report, such as is mandatory in the case of children. Most victims of assault do not figure in statistics. The establishment of an official facility for the care of adult victims is an urgent need. PMID- 1603668 TI - [Morbidity and social class in Finland, Sweden and Norway]. AB - Investigations of living standards in Norway, Sweden and Finland in 1986-1987 yielded new comparative data on public health and disease as related to social class. Long-term troublesome illness was less common in Sweden than in Finland and Norway. In all three countries the jobless category and skilled working women accounted for the highest morbidity. Among men, morbidity was greatest for agricultural workers in Finland and Norway, and lowest for Swedes of social class 1--i.e., highly placed and highly educated white collar workers. PMID- 1603669 TI - [Can the chronically ill become the chronically healthy?]. AB - Sick leave from work is on the increase throughout the Western world, despite improvements in welfare and the continual mechanization of heavy industry. By means of early, active rehabilitation measures in cases of musculoskeletal disorders, the duration of sick certification can be reduced and extended absence from work prevented. This has been demonstrated in a successful cooperative project involving the health and social services where, after two years in operation, the saving in costs to the community is calculated to have been SEK 4.5 millions. A brief outline of the project is given in the article. PMID- 1603670 TI - Drug interaction with food. PMID- 1603671 TI - [HIV and AIDS in Scandinavia]. PMID- 1603672 TI - It's not easy being green. PMID- 1603673 TI - Reader responds to a recent editorial. PMID- 1603674 TI - Enhancing adaptation to breast cancer: the addition of coaching to support groups. AB - This article describes a framework for research involving a modification of traditional cancer support groups (CSGs) that includes the presence of a caring partner who acts as a coach to facilitate the woman's adaptation to the diagnosis and treatment of breast cancer. The modified CSG and relevant response variables were derived from the Roy Adaptation Model of Nursing. Using the successful models of childbirth and diabetes education, the concept of coaching was introduced to breast CSGs. A review of the literature provides support for reduced symptom distress, reduced emotional distress, greater functional status, and higher quality of interpersonal relations as appropriate outcomes of participation in CSGs with coaching. The results of a pilot study of support groups with coaching are reported, and the goals of a currently ongoing experimental study testing the intervention have been identified. PMID- 1603675 TI - A change in flushing protocols of central venous catheters. AB - Oncology nurses working with hematology patients at the Tom Baker Cancer Centre questioned the need for twice daily flushings of central venous catheters. The nurses speculated that weekly flushings would be more convenient for patients, maintain patency, reduce risk of infections, and save the costs of supplies and nursing time. In 1986, the nurses, in collaboration with physicians, introduced a weekly flushing protocol for outpatients attending the clinic. The staff noted that no difference in rates of infection or patency appeared to result from this change in protocol. In an effort to provide empirical data in support of this fundamental shift in nursing protocols, the nurses initiated a study to examine infection rates and patency related to weekly flushing procedures. The study involved 82 patients with 89 catheter insertions. Overall infection rates were 19.1% or 0.15 per 100 catheter days. These rates were 0.25 per 100 catheter days for patients undergoing bone marrow transplant (BMT) and 0.07 per 100 catheter days in patients not undergoing BMT. Reduced patency occurred in only 13.5% of catheters studied, requiring a change in flushing protocol. When compared with published complication rates, these findings support the use of a weekly flushing protocol. As a result, staff and patients continue to use the weekly flushing protocol with greater confidence. PMID- 1603676 TI - Implementing the staff educator component of the oncology clinical nurse specialist role. AB - This article provides a brief overview of cancer nursing education, the oncology clinical nurse specialist's (OCNS's) responsibilities as staff educator, the current literature on OCNS teaching strategies, and how to choose a teaching method. A variety of creative teaching methods that facilitate effective and creative staff education are described. PMID- 1603677 TI - Gastric cancer in the Korean-American: cultural implications. AB - Although the overall incidence of gastric cancer in the United States is decreasing, Korean-Americans are increasingly at risk of developing this type of cancer. The epidemiology of gastric cancer in the Korean population is associated with environmental and genetic factors. Current treatment modalities include surgery, chemotherapy, and radiation. A case study is presented of a Korean patient who elected to participate in an investigational research protocol at the University of Southern California/Kenneth Norris Jr. Cancer Hospital. The paper also contains a discussion of transcultural nursing focusing on the background, values, and healthcare practices of Korean-Americans and the associated nursing implications. PMID- 1603679 TI - Controlling gingival bleeding with tea bags. PMID- 1603678 TI - An exploration of the variables involved when instituting a do-not-resuscitate order for patients undergoing bone marrow transplantation. AB - Written do-not-resuscitate (DNR) orders can facilitate the transition from aggressive care to supportive care in patients undergoing bone marrow transplantation who are critically ill. The DNR decision often is complicated by clinical and ethical problems. To assist nurses in analyzing these complex situations, a retrospective review was conducted on medical records of 40 patients who died on an eight-bed bone marrow transplant unit in which a formal DNR policy was in place. A review of specific variables for patients designated DNR and non-DNR showed that the groups did not vary in age, diagnosis, disease, or type of transplant. The non-DNR group developed life-threatening complications earlier in their transplant course, whereas multisystem failure was the common factor among the patients with DNR designation. The few ethical problems documented in the medical records did not appear to reflect the complexity of the DNR decision. PMID- 1603680 TI - Managing bleeding in ulcerating breast lesions. PMID- 1603681 TI - Preventing cervical bleeding with Monsel's solution. PMID- 1603682 TI - Variables predicting the need for a pediatric critical care transport team. AB - To determine when a pediatric critical care transport team is required to transport a patient to a referral center, this cross-sectional study evaluated 369 consecutive pediatric transports by stepwise multiple logistic regression analysis of six variables: age, vital signs, seizure activity, current endotracheal intubation, respiratory distress, and respiratory diagnosis. Models were developed for three outcome variables: 1) Major procedures were required in 8.9% of cases. The predicted probability of needing a major procedure was increased for intubated patients (probability of 12.9%), patients less than 1 year of age with unstable vital signs (12.9%), and patients meeting both these criteria (23.2%). 2) A posttransport assessment of need for a physician on the team was positive in 43% of cases. The probability of needing a physician was increased for intubated patients (probability of 68.8%), patients less than 1 year of age with unstable vital signs (58.7%), and patients meeting both these criteria (79.9%). 3) Category 1 drugs, ie, medications requiring ICU monitoring, were used in 19% of transports. The probability of this occurring was increased for intubated patients with stable vital signs (probability of 24.7%) and for intubated patients with unstable vital signs (41.4%). None of the other pretransport variables, alone or in pairs, was a significant predictor of any of the three outcome variables. The data indicate that intubation, age, and vital sign status can be used in predicting whether a transport team is needed. PMID- 1603683 TI - Emergency department laboratory evaluation of children with seizures: dogma or dilemma? AB - Seizure is a common problem evaluated in pediatric emergency departments. Serum chemistry analysis is often performed as a routine part of the diagnostic evaluation of children who arrive in the ED with seizure. From this retrospective study, we sought to determine 1) how often serum electrolytes (Na, K, Cl, CO2), total calcium, magnesium, ammonia, and glucose chemistries were performed, 2) the frequency of abnormalities detected, and 3) whether abnormalities resulted in a change in patient care. Three hundred eight ED charts from 12 consecutive months were reviewed. Data collected included age, sex, ED diagnosis, medical history, and physical examination. Charts were also reviewed for diagnostic tests ordered and patient management. Children were classified as having febrile (FS) or nonfebrile seizures (NFS) to establish diagnostic evaluation practices for each group as well as to determine rates of laboratory abnormalities. Three hundred eight children were enrolled, 108 (35%) FS and 200 (65%) NFS. The mean ages of FS and NFS patients were 2.1 and 5.7 years, respectively (P less than 0.05, t-test). One hundred twenty-four of 308 (40%) children had at least one test performed; no abnormal test was thought to have caused seizure; none was treated. One hundred five of 308 (34%) were experiencing their first seizure. There was no difference in the likelihood of having a test ordered for children with a first seizure, regardless of seizure category. We concluded that 1) abnormal serum electrolytes, total calcium, magnesium, and glucose rarely cause seizure in children and 2) routine use of these tests in the ED is costly and does not contribute to seizure therapy. PMID- 1603684 TI - A one-year series of pediatric emergency department wheezing visits: the Hawaii EMS-C project. AB - During a 12-month period ending on November 30, 1988, data were collected on 2468 pediatric patients with wheezing who visited a pediatric ED. Cohort characteristics included: sex (64% male, 36% female), history of prematurity (12%), evidence of concurrent infection (82%), taking theophylline (35%), taking beta adrenergics (60%), taking cromolyn (6%), and taking corticosteroids (4%). The hospitalization rate was 10.5%. Seasonal variations, weather, air quality, and infections appeared to have significant effects on the daily variation of wheezing exacerbations. Initial oxygen saturation (OSAT) correlated with disease severity as measured by hospitalization risk and the number of bronchodilator treatments required in the ED. A suggestion for categorizing the treatment of asthma based on past history is proposed. Using this system in conjunction with pulse oximetry, wheezing severity and appropriate therapy can be more objectively determined. PMID- 1603685 TI - Silver nitrate burns following treatment for umbilical granuloma. AB - Three infants treated for umbilical granuloma with silver nitrate suffered chemical burns to the periumbilical area which prompted visits to the emergency department. Treatment was conservative, and the outcome was good in all cases. We recommend caution when applying silver nitrate to the umbilicus, careful drying of the umbilical exudate to prevent spillage, and discussion with parents that burns may occur but apparently are not serious. The possibility of secondary infection is discussed. PMID- 1603686 TI - Occult supraorbital and frontal fracture. AB - The frontal region is the most common site of maxillofacial trauma in the pediatric population. Forces of enough magnitude to burst skin may also cause supraorbital and frontal bone injury. Undiagnosed skull fractures can result in grave sequelae. In cases involving blunt frontal trauma, it is important to suspect possible underlying injuries to avoid these complications. A case of a late-diagnosed, depressed supraorbital and frontal bone fracture is presented. PMID- 1603687 TI - Intravascular hemolysis associated with hydrocarbon poisoning. AB - Hydrocarbon ingestion may result in serious complications such as adult respiratory distress syndrome, encephalopathy, and seizures. Hematologic disorders have appeared to be rare complications of hydrocarbon toxicity. After encountering a case complicated by severe intravascular hemolysis, we reviewed the hospital records of all patients admitted to our pediatric intensive care unit (PICU) because of complicated hydrocarbon poisoning. Three of the 12 PICU patients identified developed intravascular hemolysis, and one developed disseminated intravascular coagulation. One patient required transfusion, but all recovered without sequelae. Intravascular hemolysis may be a more frequent complication of hydrocarbon poisoning than previously recognized. PMID- 1603688 TI - Group B streptococcus occult bacteremia. PMID- 1603689 TI - An update on the evaluation and management of plantar puncture wounds and Pseudomonas osteomyelitis. AB - The management of children who present to the ED with plantar puncture wounds is dependent upon the nature of the injury, the examination of the puncture site, and the potential risk of a retained foreign body. Not all patients will require wound enlargement and a search for a retained foreign body. Close follow-up of all children who are being treated as outpatients is of vital importance in detecting an early development of an infectious complication. Pseudomonas osteomyelitis should be suspected in all patients who present with foot pain, swelling, and a decreased ability to bear weight after sustaining a nail puncture through a sneaker. The current consensus favors open surgical debridement followed by a course of intravenous antibiotics. The exact duration of the postoperative antibiotic course is still being debated. PMID- 1603690 TI - Pediatric EMS transport: are we treating children in a system designed for adults only? AB - Unlike adults, small children and infants do not require stretchers or ambulances for transport from a prehospital scene to the emergency department (ED). This study was designed to determine the importance of this difference in patient transport needs. A Macintosh Classic computer was programmed to compare the time to intubation (TTI) of a child with impending respiratory arrest treated in a standard paramedic/ambulance transport system versus that of a child treated in a system in which a patrolling police car transports the child directly to an ED. The dependent variable TTI was determined, with travel times from the scene to the ED and paramedic intubation success rates as the independent variables. Utilizing this model, police transports demonstrate shorter TTIs for brief scene to-ED travel times or limited paramedic success rates, while paramedic intubations produced shorter TTIs for long scene-to-ED transports. These results suggest that nonambulance transport of pediatric patients be considered in the development of urban or suburban pediatric Emergency Medical Services. PMID- 1603691 TI - Abdominal pain and anorexia. PMID- 1603692 TI - Abdominal pain. PMID- 1603693 TI - Acute testicular pain: Henoch-Schonlein purpura versus testicular torsion. AB - A skilled examiner may not be able to exclude testicular torsion by physical examination maneuvers in a patient who presents with acute scrotal pain. Diagnostic adjunctive studies may be of assistance. However, if a diagnosis cannot be established with certainty, surgical exploration is warranted. Patients with Henoch-Schonlein purpura who present with a vascular eruption on the scrotum, lack a rash elsewhere, and have no arthritis or hematuria are likely to be explored. PMID- 1603694 TI - Infrared ear thermometry. AB - Many hospitals are considering using infrared (IR) ear thermometers (also called tympanic membrane thermometers) as an alternative to traditional temperature measurement devices. IR technology allows users to quickly and noninvasively measure body temperature by inserting a directional probe into the ear canal. For infection control, ear thermometers offer the advantages of not contacting mucous membranes and eliminating the need for special handling procedures. For use on unconscious patients or those who are otherwise unwilling or unable to cooperate with traditional techniques, IR ear thermometers offer a more comfortable and less stressful method of temperature taking for both patients and nurses, especially where rectal temperatures are used. The recent entry into this market by major companies and distributors and the release of several new IR ear thermometers have helped to further stimulate interest in this technology. However, a complete transition to IR ear thermometers throughout the hospital may not be necessary and should be made only after these devices have been successfully used in selected clinical locations, such as emergency departments, critical care areas, recovery areas, and labor and delivery rooms. Clinical users must be familiar with the technique needed for temperature measurement with these instruments and understand the differences between temperatures taken in the ear canal and those obtained from traditional sites. In the following article, we first present an overview of clinical thermometry, describing traditional temperature-measurement sites and devices. We then discuss the advantages and disadvantages of using the ear canal, including the tympanic membrane (TM), as a site for temperature measurement. In addition, we guide readers in determining the usefulness of IR ear thermometers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603695 TI - A 15 year old with palpitations and dizziness. PMID- 1603696 TI - Tympanic membrane thermometer in the measurement of temperature in children. PMID- 1603697 TI - Ondine's curse and sudden infant death syndrome. PMID- 1603698 TI - The prehospital treatment of pediatric trauma. AB - Prehospital pediatric trauma care is an important part of the EMS system. Review of 458 pediatric ALS trauma responses over two years treated in an urban, tiered ALS system revealed a male predominance. Violence (gunshot, stab, or assault) accounted for 46% of injuries, followed by vehicular accidents (occupant or pedestrian), with 35%. Important ALS resuscitation interventions were commonly performed en route, with a high degree of success (IVs = 93%, intubation = 79%), and did not greatly prolong field times (9 min BLS vs 11.7 min ALS). ALS procedure success rates and field times reported here are lower than previously described. Benchmark standards for the prehospital care of pediatric trauma are proposed. PMID- 1603699 TI - Painless limp. PMID- 1603700 TI - The wheezer that wasn't. AB - The expression of cardiac dysfunction in pediatric patients with myocarditis may not be conspicuous. While older children with myocarditis may abruptly present with pleuritic or angina-like pain, infants and toddlers with fulminant disease are unable to verbalize such complaints. Cardiac compromise in preverbal children may only be inferred from variable examination findings that include gallop rhythm, tachycardia, malignant dysrhythmias, murmur, rub, and signs of congestive heart failure. The emergency physician is likely to overlook a cardiac origin for wheezing in a child with a past medical history of asthma. Therapeutic modalities chosen for reactive airway disease may adversely influence the outcome of a patient with myocarditis. PMID- 1603701 TI - Cribs. PMID- 1603702 TI - Absence of serum chemistry abnormalities in pediatric patients presenting with seizures. AB - To determine the utility of the routine practice of obtaining serum chemistry values on children presenting after a seizure, we reviewed the emergency department records of 241 episodes of seizures in pediatric patients. One hundred fifty-five nonfebrile (49 initial, 106 recurrent) and 86 febrile (53 initial, 33 recurrent) convulsive episodes were analyzed. At least one serum chemistry value was obtained in 149 (64%) patients. Clinically significant abnormalities were found in 0/149 serum sodium, 0/148 glucose and blood urea nitrogen, 0/86 calcium, and 0/61 magnesium studies. We concluded that routine determination of serum chemistry values in pediatric patients presenting with a seizure is unnecessary unless specific clinical data strongly suggest otherwise. PMID- 1603703 TI - Seizures associated with meningitis. AB - The records of 187 patients with bacterial meningitis were reviewed. Seizures were a presenting manifestation in 25 (13%). Seven (28%) of the patients with a presenting seizure had been taking antibiotics prior to the diagnosis. Four of seven pretreated patients did not have additional signs or symptoms with the seizure, while all 18 patients without treatment had additional findings (P less than 0.01). Patients developing seizures while hospitalized had a poorer outcome than those without seizures. Patients with bacterial meningitis may present with only a seizure if they have been taking oral antibiotics; therefore, all patients taking antibiotics who develop a seizure require a lumbar puncture to exclude meningitis. PMID- 1603704 TI - The Hawaii EMS-C project data: I. Reducing pediatric emergency morbidity and mortality; II. Statewide pediatric emergency registry to monitor morbidity and morality. AB - During a 12-month period ending on 11/30/88, data were collected on 16,010 pediatric patients who visited a pediatric emergency department (ED). These ED patients prospectively fell into one of the target areas for further study, including wheezing (15%), trauma (excluding burns; 29%), burns (1%), water related injuries (1%), ingestions and toxic substance exposures (2%), child abuse (3%), handicapping conditions (5%), preventable incidents (33%), and ambulance arrivals (7%). Handicapped patients were more likely to require an ambulance. Younger patients, males, and patients with handicaps, wheezing, and Medicaid insurance were more likely to visit the ED on multiple occasions. Primary care physicians could be identified in 77% of the cohort. Large-scale interventions to reduce preventable pediatric morbidity and mortality have suffered from difficulties in documenting their effect in a population-based sample. A statewide pediatric emergency encounter registry is proposed. PMID- 1603705 TI - Pediatric intramuscular injections: do you know the procedure and complications? AB - The practice of outpatient intramuscular antibiotic therapy for infants and children at risk for serious bacterial infections is an attractive alternative to hospitalization. The use of this alternative is likely to increase. Pediatric emergency physicians and pediatric residents at our institution were surveyed to determine their knowledge of intramuscular injection techniques. The dorsogluteal site is contraindicated in infants and children, but it was selected for 14 (21%) of the patients presented in the survey. One-inch needles are recommended for children 0 to 24 months of age, but 1 1/2-inch needles were preferred for 13 (30%) of these younger children. A volume of 1 ml to be injected at one site was exceeded 10 (47%) times. Such practices increase the risk for infectious complications and neurovascular and muscle injuries. To avoid these complications, guidelines for pediatric intramuscular injections are presented. PMID- 1603706 TI - Cocaine toxicity in an infant following intranasal instillation of a four percent cocaine solution. AB - An 11-week-old infant experienced toxicity following the intranasal instillation of a four percent cocaine solution in preparation for an examination to rule out choanal stenosis. The child recovered fully but required the use of anticonvulsants and admission to the hospital. To our knowledge, this is the first case report where cocaine toxicity was experienced following this routine practice. We present our case and a review of the literature involving other instances where there have been complications with the use of topical cocaine. This report should alert the medical community to the potential complications of using topical cocaine for its anesthetic properties. PMID- 1603707 TI - Spinal epidural abscess in children: two illustrative cases. AB - The diagnosis of spinal epidural abscess is often delayed until the onset of rapidly deteriorating neurologic function. To illustrate the variability of presenting symptoms with this disease, two contrasting cases are presented. The pathogenesis of the disorder, bacterial etiologies, diagnostic modalities, and treatment alternatives are discussed. PMID- 1603708 TI - Elevated lead levels in a patient with sickle cell disease and inappropriate secretion of antidiuretic hormone. AB - A five-year-old girl with known sickle cell disease presented with severe hyponatremia and findings compatible with syndrome of inappropriate secretion of antidiuretic hormone (SIADH). She was found to have lead levels in the Class III category. By exclusion, we postulated that the SIADH was in some way related to the high lead levels, since this was the only abnormality the patient exhibited. The toxic lead levels and the elevated vasopressin levels rapidly responded to dimercaprol and calcium EDTA chelation therapy. PMID- 1603709 TI - Popsicle panniculitis. PMID- 1603710 TI - Endotracheal drug delivery. PMID- 1603711 TI - The role of the emergency department in primary care. PMID- 1603712 TI - Effects of respiration on right ventricular size and function: an echocardiographic study. AB - The effects of quiet respiration and body position on right ventricular (RV) size and function were assessed by two-dimensional (2DE) and M-mode echocardiography in 15 healthy children. All end-diastolic echocardiographic dimensions, areas, and volumes increased slightly but significantly with inspiration. At end-systole similar changes were found. RV ejection fractions were significantly higher during inspiration, as were stroke volume indices. RV dimensions also increased from supine to left lateral decubitus position. Thus, our results indicate a need for standardization of 2DE and M-mode measurements not only for body position, but also for respiratory phase when used to assess RV size and function. PMID- 1603713 TI - Left ventricular performance in neonates on extracorporeal membrane oxygenation. AB - The evaluation of left ventricular systolic performance in infants undergoing extracorporeal membrane oxygenation (ECMO) using traditional ejection-phase indices is hampered by significant alterations in preload and afterload. Therefore, a load-independent index, which relates heart-rate-corrected mean velocity of circumferential fiber shortening (VCFc) to afterload, measured as end systolic wall stress (ESS), was used to assess left ventricular function in 18 term neonates undergoing ECMO. The mean age at the onset of ECMO was 75.5 h and the duration of therapy was 171 +/- 106 h. Left ventricular performance was highest before the onset of ECMO (VCFc = 1.65 +/- 0.49 circ/s) and decreased toward normal during (1.38 +/- 0.33 circ/s) and following ECMO (1.29 +/- 0.16 circ/s). Initially, nine of 17 (53%) patients had enhanced performance for the degree of afterload but in only 16 of 48 (33%) studies during ECMO and none following ECMO was VCFc elevated beyond the normal range predicted for ESS. These changes in left ventricular performance may be the result of variations in exogenous, as well as endogenous, catecholamines rather than intrinsic alterations in myocardial contractility. It is concluded that the VCFc/ESS relation permits a meaningful assessment of ventricular performance in critically ill neonates undergoing ECMO. PMID- 1603714 TI - Effect of increase in heart rate on interatrial shunt in atrial septal defect. AB - The effect of increases in heart rate by atrial pacing was investigated in 20 children [mean 9 +/- 4 (SD) years] with atrial septal defect. Systemic blood flow increased by 13 +/- 10 and 27 +/- 22% with a 25 and 50% increase in heart rate, respectively. Pulmonary blood flow, however, remained unaltered. Thus, rapid pacing decreased the pulmonary to systemic blood flow ratio significantly (-15 +/ 10 and -22 +/- 13%, respectively). This hemodynamic alteration was attributed to the difference in diastolic distensibility (compliance) between the left and right ventricles, and the ratio of right ventricular to left ventricular compliance (defined by dV/dP) near the end-diastolic pressure was estimated to be 6.5 +/- 4.2. It is suspected that the increase in heart rate may contribute to the lowering of pulmonary to systemic flow ratio during exercise in children with atrial septal defect. PMID- 1603715 TI - Children with congenital heart disease: probability of natural survival. AB - The age distribution of death in all children with congenital heart disease (CHD), who died in a 27-year period in Central Bohemia (population of 1.2 million), and the data on the incidence of CHD in children born in Bohemia (population of 6.3 million) in 1980 were used to calculate the probability of survival of a child born with CHD. Eighty-six percent of these children survived to the first month of life--mostly those with pulmonary stenosis (PS, 99%), aortic stenosis (AS, 95%), ventricular septal defect (VSD, 92%), and atrioventricular septal defect (AVSD, 91%). Seventy-one percent of patients survived the first year of life--mostly those with PS (97%), AS (91%), atrial septal defect (ASD, 89%), VSD (80%), and persistent ductus arteriosus (PDA, 78%). In total, 67% of CHD patients can be expected to survive childhood. The highest survival rates were found in PS (94%), AS and ASD (84%), VSD and PDA (70-80%), and coarctation of the aorta (COA, 68%). The survival rate for the remaining forms of CHD was less than 50%. The highest mortality rate (10% of all children born with CHD) can be expected in the first postnatal week. The lowest survival in the first week was found among those with hypoplastic left heart (HLHS, 39%), double-outlet right ventricle (DORV, 50%), truncus arteriosus (TrA, 57%), pulmonary atresia (PA, 70%), and transposition of the great arteries (TGA, 83%). In addition, total anomalous pulmonary venous connection (TAPVC) and single ventricle had the highest risk of death in the first year of life. PMID- 1603716 TI - Association of distal displacement of the left subclavian artery and coarctation of the aorta. AB - Previously noted but undocumented observation of distal displacement of the left subclavian artery in patients with discrete coarctation of the aorta was verified by an objective two-dimensional echocardiographic method in 28 patients with aortic coarctation and in 43 control subjects. Relative position of brachiocephalic arteries to one another was evaluated by the ratio of the distance between the left common carotid and the left subclavian artery to the distance between the innominate and the left common carotid artery. Large distance between the left common carotid and the left subclavian artery was reflected by high value of the derived ratio. In neonates with aortic coarctation, the ratio was 1.69, SD +/- 0.66, compared to 1.04, SD +/- 0.40 in the control group. In older children this ratio was less discriminatory. We also observed that the left subclavian artery formed an acute angle (less than 90 degrees) with the proximal (upstream) segment of the aortic arch in infants with aortic coarctation. In all control infants, this angle was equal to or greater than 90 degrees. A corresponding necropsy study confirmed the echocardiographic findings. We conclude that distal displacement of the left subclavian artery is associated with coarctation of the aorta. It can be accurately visualized and objectively assessed by the two-dimensional echocardiographic technique proposed. PMID- 1603717 TI - Supravalvar aortic stenosis: discordance in monozygotic twins and reduction in severity of obstruction during childhood. AB - A monozygotic twin boy with supravalvar aortic stenosis had reduction in the degree of obstruction with body growth. His twin brother had normal cardiac anatomy. To our knowledge, this is the first report of improvement without intervention in a patient with supravalvar aortic stenosis and of discordance of supravalvar aortic stenosis in monozygotic twins. PMID- 1603718 TI - Development of a left atrial ball thrombus in a woman with complex congenital heart disease including congenital mitral valve stenosis. AB - A 20-year-old woman with complex cyanotic congenital heart disease, including severe congenital mitral stenosis and intact atrial septum, who developed a left atrial ball thrombus and an embolic phenomenon, is presented. Increased vigilance in this unique setting is necessary for the antemortem detection of this rare complication. PMID- 1603719 TI - Transient complete heart block following percutaneous balloon pulmonary valvuloplasty: treatment with systemic corticosteroids. AB - Balloon pulmonary valvuloplasty is a safe and effective treatment for congenital pulmonic valve stenosis. This report describes a child who developed complete atrioventricular (AV) block following balloon pulmonary valvuloplasty. The child was treated with a 10-day course of systemic corticosteroids. The heart block gradually resolved during the first week following the procedure and has not recurred. Heart block is a known complication of right heart catheterization and has been described following balloon pulmonary valvuloplasty. Systemic corticosteroids have been used to treat AV block of various etiologies and may have contributed to the child's recovery in this case. PMID- 1603720 TI - Transient third-degree atrioventricular block in a 4-year-old child with familial dysautonomia. AB - The case of a transient third degree atrioventricular block in a 4-year-old patient with familial dysautonomia is reported. A review of the literature follows with analysis of the significance of arrhythmias in the natural history of the patient with familial dysautonomia. PMID- 1603721 TI - Total anomalous pulmonary venous connection: persistence and atresia of the common pulmonary vein. PMID- 1603722 TI - Spontaneous closure of ventricular septal defects. PMID- 1603723 TI - The interface of psychiatry and neurology. PMID- 1603725 TI - The simulation of neurologic disease. AB - Conversion symptoms are defined as symptoms that suggest neurologic disease but have no explanation after appropriate evaluation including physical examination, laboratory studies, and appropriate radiographic and other imaging studies. Conversion symptoms are more common in young women as compared with other groups. Conversion symptoms may be seen in essentially all psychiatric illness categories and are especially common in Briquet's syndrome and antisocial personality disorder. They are also seen in patients with neurologic disorders, including seizure disorder, central nervous system tumor, head injury, and multiple sclerosis. Family members of patients with conversion symptoms have a heterogeneous mixture of psychiatric illnesses parallel to the heterogeneous conditions seen in the probands. Psychosocial stressors and compensation factors, including monetary and legal aspects, appear to play important roles in many cases of conversion symptoms. Most individual conversion symptoms resolve, but the individual patient may experience other conversion symptoms as well as experience difficulty as a result of comorbid psychiatric illness. PMID- 1603724 TI - Neuropsychological assessment. AB - The aging population of the United States and many other countries guarantees that disorders common in elderly persons will continue to become more prevalent. In the past decade or so, we already have witnessed the beginning of this trend, with the rapid rise in the number of patients with degenerative dementia, especially Alzheimer's disease. On another track, sophisticated and timely medical and surgical interventions have produced a growing number of patients who survive serious head injury. These patients are typically young, and may live for many decades after their brain injury. In both examples, a core feature of the condition is impaired cognition and behavior; that is, defects in higher-level capacities such as memory, intellectual function, language, and decision-making. Neuropsychological assessment cannot be viewed as a luxury in cases such as these but rather, as a vital component of the neurodiagnostic evaluation. The neuropsychologist uses a set of standardized instruments to measure cognition and behavior in a comprehensive and precise manner, yielding rich information that may assist in accurate diagnosis, prudent management, and optimal rehabilitation. The neuropsychological examination may provide the only means with which to detect alterations in brain function, as in cases of mild head injury or low level toxic exposure, which may not be revealed through other procedures. Finally, neuropsychological assessment will continue to play a key role in the scientific programs that are dedicated to advancing our understanding of the neural substrates of complex behavior. PMID- 1603726 TI - Neurologic conditions presenting as psychiatric disorders. AB - Neurologic disease can present as a psychiatric disorder. Understanding underlying neuroanatomic function helps physicians to localize defects and search for treatable neurologic conditions. Neurologic conditions such as Huntington's chorea, Wilson's disease, Gille de la Tourette syndrome, brain tumors, encephalitis and meningitis, neurodegenerative conditions and metabolic or toxic conditions can have psychiatric manifestations. PMID- 1603727 TI - Update on delirium. AB - Delirium is a common syndrome in hospitalized medical and surgical patients and in those seen in emergency departments. It is particularly common in the demented elderly patients. To prevent it, for example by avoiding polypharmacy in the elderly, is important. It is most important to diagnose delirium early and to search for its cause without delay as this may be life-saving in some patients and may help avoid injury in others. This syndrome, long neglected by investigators, calls for vigorous research to establish its epidemiology, pathogenesis, and long-term outcome. PMID- 1603728 TI - Visual, somatosensory, olfactory, and gustatory hallucinations. AB - Hallucinations that involve any of the sensory modalities may accompany a number of functional and organic conditions. Although characteristics of the hallucinations are not specific, they are characteristic and suggestive of specific disorders. Appropriate evaluation and treatment require consideration of the past psychiatric, neurologic, and medical history; assessment of accompanying psychiatric and neurologic signs and symptoms; and degree of response to conventional therapy. Any patient with hallucinations of recent onset or presenting a significant change in the nature of prior hallucinations, particularly when the patient does not respond to conventional therapy, deserves an evaluation to rule out treatable organic factors. PMID- 1603729 TI - Neurologic complications of alcoholism. AB - Alcohol is still the most abused drug today and may affect the peripheral, central, and autonomic nervous system in many ways. There are several pathophysiologic mechanisms that include direct effects through intoxication, withdrawal effects, secondary effects from nutritional problems and systemic diseases, and, of course, syndromes of unknown etiology. The alcoholic is also susceptible to trauma to both the central and peripheral nervous system. In many of the clinical entities, multiple factors play a role. PMID- 1603730 TI - Complex partial seizures. Clinical features and differential diagnosis. AB - Complex partial seizures are the most common seizure type in patients with partial epilepsy. Most complex partial seizures emanate from the temporal lobe; however, the seizures also may be extratemporal in origin. The clinical phenomenology may distinguish complex partial seizures from nonepileptic paroxysmal disorders and other seizure types. Physiologic and psychological disorders need to be considered in the differential diagnosis of seizure activity. Long-term EEG monitoring may be necessary for select patients to confirm the diagnosis of epilepsy and to classify appropriately seizure type. Carbamazepine and phenytoin are the antiepileptic drugs of choice in the management of complex partial seizures. Polypharmacy and use of cognitively impairing antiepileptic drugs may reduce patient compliance and further impair the quality of life of the patient with epilepsy. Finally, epilepsy surgery is an important alternative for the patient with intractable partial seizures. PMID- 1603731 TI - Neuropsychological aspects of epilepsy. AB - Brain dysfunction between seizures is common in epilepsy and a systematic assessment of it assists in planning directed programs of remediation. A battery of well-validated neuropsychological tests formulated with the needs of persons with epilepsy in mind can be of particular help in this regard. Increasing impairment in brain functions is shown to be associated with increasing emotional problems. Medical variables pertaining to seizure history include seizure type, cause, age at onset of seizures, duration of disorder, and seizure frequency. An exploration of relationships between these variables and measures of abilities and adjustment reveals a number of findings, some of which are complex. A review of the cognitive effects of antiepileptic drugs shows that the barbiturates have at least slightly greater adverse cognitive and behavioral effects than other drugs including carbamazepine, phenytoin, and sodium valproate. Whether cognitive differences exist among these latter medications is currently in question. Carbamazepine has the best-established favorable psychiatric effect. PMID- 1603732 TI - Neuropsychiatric sequelae of head injuries. AB - Based on the above review several general points can be highlighted: Head injuries are extremely common, affecting probably close to 2,000,000 people in this country each year. The most common are nonmissile, closed-head injuries, the majority of which occur in association with motor vehicle accidents. Virtually all studies of head injury suggest a peak incidence in the 15 to 24 years of age group. Coarse measures of outcome suggest that the very young and the elderly have poorer outcomes. Because of improved acute care, however, a large number of young, otherwise healthy patients are surviving head injuries with a variety of profound neuropsychiatric sequelae. Because of the mechanics of brain injury in acceleration-deceleration injuries, certain brain injury profiles are common including orbitofrontal, anterior and inferior temporal contusions, and diffuse axonal injury. The latter particularly affects the corpus callosum, superior cerebellar peduncle, basal ganglia, and periventricular white matter. The neuropsychiatric sequelae follow from the above injury profiles. Cognitive impairment is often diffuse with more prominent deficits in rate of information processing, attention, memory, cognitive flexibility, and problem solving. Prominent impulsivity, affective instability, and disinhibition are seen frequently, secondary to injury to frontal, temporal, and limbic areas. In association with the typical cognitive deficits, these sequelae characterize the frequently noted "personality changes" in TBI patients. In addition, these changes can exacerbate premorbid problems with impulse control. Marked difficulties with substance use, sexual expression, and aggression often result. The constellation of symptoms, which make up the postconcussive syndrome, are seen across the whole spectrum of brain injury severity. Even in so-called mild or minor head injury, these symptoms are likely to have an underlying neuropathologic, neurochemical, or neurophysiologic cause. Higher than expected rates of certain psychopathologic disorders occur in the TBI population, including psychotic syndromes and depressive syndromes. Manic syndromes also are associated with TBI; however, the incidence has not been established. Assessment and treatment of the neuropsychiatric sequelae is a complex and challenging process. The mixture of diffuse and focal injuries, the combination of cognitive, language, somatic, and behavioral difficulties do not fit easily into current diagnostic categories. PMID- 1603733 TI - Behavioral neurology and stroke. AB - The role that stroke patients have played in the history of behavioral neurology was illustrated by describing some contributions made by Broca, Dejerine, Wilbrand, Liepman, and Geschwind. The recent work on the anatomic basis of recovery or lack of recovery in aphasia was discussed and the network of structures important in attention were reviewed. The study of stroke patients with amnestic syndromes (particularly those with basal forebrain and diencephalic lesions) was discussed as well. Starting with Liepman's classic contribution, and then looking at more recent studies, the left hemisphere's role in limb praxis was analyzed. The different syndromes that result when the superior and inferior visual association cortices are damaged were described and illustrated. A summary of neurobehavioral syndromes related to stroke that may present to the psychiatrist because the patient does not have an hemiparesis was given. The relationship of stroke to dementia and depression was reviewed. PMID- 1603734 TI - Behavioral manifestations associated with multiple sclerosis. AB - The behavioral manifestations associated with MS include both cognitive and emotional disturbances. Overall intellect is slightly affected in about half of patients, and 20% to 33% demonstrate more severe impairments. Memory disturbances are particularly common, and retrieval function is especially affected. Difficulties with concept formation and other executive functions can be subtle yet have significant impact on daily living. Depression is frequent in MS, sometimes despite an outward euphoria that is more prevalent with advancing disease. Psychosis occurs rarely, but bipolar disorder is more frequent than in the general population. MS may be associated with a variety of personality changes, but it is impossible to generalize about this or to identify an "MS personality." Disturbances of emotional control are relatively frequent. Comprehensive management of these problems uses multiple modalities including good neurologic care, cognitive rehabilitation, counseling and support groups, and pharmacotherapy. PMID- 1603735 TI - Systemic lupus erythematosus with central nervous system involvement. AB - Real or suspected brain involvement occurs in the majority of patients with systemic lupus erythematosus. The clinical manifestations are myriad and are accounted for by diverse pathogenic mechanisms. Purely psychological disturbances and psychiatric syndromes with organic components account for the majority of cases. Metabolic disturbances, drug effects, and infections may masquerade for immune-related brain dysfunction. In the absence of reliable and specific indicators of lupus brain activity, successful management requires the combined skills and clinical judgment of the rheumatologist, neurologist, and psychiatrist. PMID- 1603736 TI - Update on disorders of sleep and the sleep--wake cycle. AB - Wakefulness and sleep are antagonistic states competing for the domain of brain activity. Non-REM sleep and REM sleep are different states of being, sustained by activity in brainstem nuclei, hypothalamus, basal forebrain, and thalamus. Such complex phenomenology is subject to many alterations grouped in the new International Classification of Sleep Disorders. The insomnias are the result of interacting psychosocial, psychophysiologic, neurodevelopmental, and medical factors. Proper perspective of each factor provides the clinical strategies to approach medically the symptom-complex of insomnia. The most common cause of daytime hypersomnia is chronic sleep deprivation. Obstructive sleep apnea responds to nasal CPAP, but the failure rate approaches 30%. In intolerant patients BiPAP and surgical remedies should be considered. Motor and behavioral abnormalities of sleep may be linked to REM sleep as in the REM sleep behavior disorder. Paroxysmal nocturnal dystonia and nocturnal wanderings may be associated with epilepsy. Intrusions of one state of being (wakefulness, non-REM sleep, and REM sleep) into another result in mixed, poorly defined, or only partially developed states. Dissociation of states may be responsible for confusional arousals, hallucinations, and cateplexy. Senile degeneration of the suprachiasmatic nuclei may underlie the circadian rhythm changes in old age and the "sundown" syndrome in demented patients. Misalignment of the hypothalamic pacemaker causes dysregulation of sleep-related physiologic and behavioral variables. Exposure to bright light retrains the pacemaker in night-shift workers, transmeridian travelers, and in patients with seasonal affective syndrome. Benzodiazepine compounds are very effective hypnotics, but should be used sparingly in the elderly to avoid falls, memory lapses, and aggravation of a preexisting sleep apnea syndrome. Sleep laboratory evaluations are indicated in patients with hypersomnia, suspected sleep apnea syndrome, motor-behavioral disorders of sleep, and in many individuals complaining of insomnia. PMID- 1603737 TI - Mental retardation. AB - Mental retardation is defined using two criteria: intelligence quotient and adaptive functioning. Subclassification based on IQ is helpful in predicting outcome and determining educational program. Advances continue to be made in identifying specific medical causes of intellectual deficits. As the natural history of conditions such as fragile-X becomes better understood, treatment approaches based on medical diagnosis will likely evolve. Clinicians working with mentally retarded patients should pursue vigorously medical diagnosis because of its implications for genetic counseling, family management, and full recognition of other handicapping conditions which may affect the patient. Psychopathology in the mentally retarded resembles that in nonretarded individuals, but occurs more frequently. Treatment of psychiatric disorders must be individualized. Mildly and some moderately retarded persons can benefit from psychotherapy. Behavioral approaches, particularly applied behavior analysis, are the most effective treatment for specific aberrant behaviors. Pharmacotherapy should be based on psychiatric diagnosis. Medications may be used, together with behavioral interventions, to treat specific destructive behaviors, but the scientific support for such use is new and somewhat limited. PMID- 1603738 TI - Infantile condylomata of the oral cavity. AB - A child had condylomata acuminata localized to the oral cavity. Main points of interest were this exclusive localization, the extremely high number of papillary lesions, not reported in the literature until now, and the excellent response to interferon and local applications of podophyllin. Histologic, ultrastructural, and in situ molecular hybridization techniques were performed to make a correct diagnosis. Transmission of the etiologic agent and therapeutic approaches are discussed. PMID- 1603739 TI - Unusual physiologic melanin pigmentation of the tongue. AB - A patient had extensive congenital oral hyperpigmentation of the tongue. The clinical and histologic features set this case apart from any well-delineated disease. Clinically, the congenital onset, the appearance of large black-brownish lesions, the lack of associated systemic abnormalities, and the histologic findings of prominent deposition of melanin in the basal layer support the diagnosis of physiologic melanosis. The macular lesions of the tongue represent discrete depositions of melanin and exemplify soft tissue pigmentation of developmental origin. PMID- 1603740 TI - EMLA cream: an improved local anesthetic. Review of current literature. PMID- 1603741 TI - Anesthesia and/or sedation for pulsed dye laser therapy. PMID- 1603742 TI - Segmental eruption in an 8-year-old girl. PMID- 1603743 TI - Erythema toxicum present at birth. PMID- 1603744 TI - Blue rubber bleb nevus syndrome: laser photocoagulation of colonic hemangiomas in a child with microcytic anemia. AB - This is a case report and review of the literature on the blue rubber bleb nevus syndrome. The clinical features of the syndrome are discussed, with emphasis on chronic gastrointestinal bleeding and resulting anemia. A new therapeutic modality, colonoscopy with laser photocoagulation, is recommended as a safe, effective, and less invasive method of controlling bleeding from colonic hemangiomas than surgical resection and repeated transfusions. This technique is less helpful for patients with prominent involvement of the small intestine. PMID- 1603745 TI - Self-healing collodion baby: evidence for autosomal recessive inheritance. AB - Five spontaneously healing collodion babies were recorded in a large Swiss kindred. They all had consanguineous parents. Their distribution in the family indicates autosomal recessive inheritance. At birth they had the typical features of collodion babies. The collodion-like membrane was shed within the first month, leaving a slightly scaly skin for a few weeks. Thereafter the skin remained normal without any evidence of a disorder of cornification. PMID- 1603746 TI - Current therapy for HIV infection and its infectious complications. A practical summary for primary care physicians. AB - Primary care physicians can play a crucial role in the care of patients with HIV infection. Treatment often requires orchestration of many complex drug regimens. In addition, the patient must make informed decisions about a broad range of care related issues. Steps in the care of such patients include (1) staging of HIV infection, (2) instituting antiretroviral therapy, and (3) preventing opportunistic infections plus treating opportunistic infections when present. A wide range of established and investigational agents are available for these purposes, and new ones are continually being discovered. PMID- 1603747 TI - Preventing HIV transmission. Strategies to protect clinicians and patients. AB - Human immunodeficiency virus (HIV) transmission to healthcare workers arises primarily from percutaneous injury by sharp devices recently contaminated with infected blood. The danger is small but real, and substantial effort to reduce this risk is justified. The risk of transmission to patients from HIV-infected healthcare workers is much smaller. Attempts to accommodate measures to control this risk in standard protocols has engendered considerable debate. The discrimination and loss of insurability attendant to HIV infection also complicate the application of control measures. Where possible, procedures appropriate in cases involving known HIV infection should be applied in all situations. Acquiring tuberculosis from HIV-infected patients probably presents a greater hazard to healthcare workers than becoming infected with HIV itself. PMID- 1603748 TI - Evaluation of chest pain. Back to the basics of history taking and physical examination. AB - Although careful history taking and physical examination seem to have been supplanted in some parts of modern medicine by expensive and high-tech laboratory tests, evaluation of chest pain is an exception. It still depends on careful attention to the basics of a directed line of history taking and physical examination. Careful correlation of the details elicited with the pathophysiology of myocardial ischemia leads the astute clinician through the maze of various causes of chest pain to the proper final diagnosis. PMID- 1603749 TI - 'Designer drugs'. Recognizing and managing their toxic effects. AB - "Adam," "Eve," "ecstasy," "China white." Illicit street drugs such as these are called designer drugs because they are designed to elicit certain effects and to bypass legal classification. Unfortunately, use and abuse of such substances can lead to serious medical problems and even death. Drs Sternbach and Varon describe the best-known compounds and discuss clinical characteristics and management of designer drug intoxication. PMID- 1603750 TI - Diabetic diarrhea. An underdiagnosed complication? AB - Diarrhea is a common gastrointestinal problem in diabetes, and its prevalence has been underestimated. The cause of diabetic diarrhea is unknown, but it is probably related to gastrointestinal motility disturbances secondary to diabetic autonomic neuropathy. Other causes (especially primary malabsorption syndromes and islet cell tumors) must be excluded. Treatment of diabetic diarrhea is largely symptomatic and only moderately effective. Antidiarrheal agents may ameliorate acute episodes. Broad-spectrum antibiotics and clonidine hydrochloride (Catapres) have had some success in long-term control. Most recently, subcutaneous administration of somatostatin analogues has been shown to be helpful, the main side effects being drowsiness and vomiting. PMID- 1603751 TI - Over-the-counter medications. Do you know what your patients are taking? AB - The pharmacopeia of over-the-counter (OTC) drugs is ever expanding, and many of these nonprescription agents cause a variety of adverse drug-drug and drug patient interactions. It is therefore essential that physicians be aware of the more than 700 active ingredients available in OTC drugs at the local store and make a concerted effort to identify which ones their patients are taking. Healthcare providers also need to educate patients about the potential effects of OTC drugs and encourage them to consult either their physician or their pharmacist before attempting self-medication. PMID- 1603752 TI - 'Play-or-pay'. A slippery slope to an all-government healthcare system. PMID- 1603753 TI - A new era in hypertension therapy. Protecting patients from premature cardiovascular disease. AB - Although the cause of hypertension in most patients is unknown, many patients have coexisting risk factors that may contribute to the disease. According to Dr Kaplan, the key to effective treatment is an individualized approach that maximizes blood pressure control by addressing each patient's profile of risk factors. In this article, he discusses various coronary risk factors and recommends appropriate drug and nondrug therapies. PMID- 1603754 TI - Preventing falls in the elderly. A practical approach to a common problem. AB - Considerable morbidity and mortality occur among the elderly every year in the United States as a result of falls. Assessing the risk of falling with use of thorough history taking, physical examination, and special tests of balance and gait allows physicians to make specific safety recommendations. PMID- 1603755 TI - Gallstone obstruction of the colon. Thorough treatment prevents serious complications. AB - Formation of a fistula between the gallbladder and bowel may allow a gallstone to enter the intestinal tract. In the two cases described here, the colon was involved. The authors describe diagnosis and management of these cases and make treatment recommendations based on their experience. PMID- 1603756 TI - Predicting outcome in brain-injured patients. Using the Glasgow Coma Scale in primary care practice. AB - The Glasgow Coma Scale provides a quick and simple way to assess the level of consciousness of a brain-injured patient and to predict that patient's social outcome. The information provided by such prediction of prognosis can help primary care physicians choose the appropriate therapeutic regimen and also allows investigators to compare alternative regimens. PMID- 1603757 TI - Otosclerosis. Treating progressive hearing loss in young adults. AB - When a patient presents with bilateral progressive hearing loss and has a family history of hearing loss, otosclerosis should be placed high on the list of possible causes. Primary care physicians should determined whether the hearing loss is conductive or sensorineural with otologic examination and tuning-fork evaluation. Unless there is an obvious reversible cause for the progressive hearing loss, the patient should be referred to an otolaryngologist for more intensive otologic and audiologic examination. The patient's principal concern is the ability to hear and comprehend the spoken word in normal circumstances. Fortunately, most patients can be rehabilitated with surgery or a hearing aid. Fluoride treatment may have a significant role in preventing further hearing loss from otosclerosis. PMID- 1603758 TI - Hematopoietic growth factors. A promising future for use in bone marrow dysfunction. AB - The clinical future of hematopoietic growth factors appears promising. They will probably achieve broad clinical application in a wide variety of hematologic disorders. Their use in infectious diseases associated with granulocytopenia and in cancer-treatment regimens as adjuvant agents against myelosuppression and perhaps as stimulants of the natural anti-cancer effects of host cells also seems appropriate. PMID- 1603759 TI - Cavitary lung disease. How to read the radiographic patterns. AB - Many disorders and abnormalities are accompanied by cavitary lesions of the lung, including various diseases that may destroy or replace lung tissue. The most common causes of cavitary lung disease are primary and metastatic neoplasms, granulomas, and necrotizing pulmonary infections. These diseases often have radiographic patterns, clinical signs, and symptoms that are characteristic and may suggest a diagnosis. PMID- 1603760 TI - Reasons for the rise in healthcare costs. PMID- 1603761 TI - Free-market healthcare system. PMID- 1603762 TI - Clarification. Drug therapy for hyperlipidemia: when reducing cardiovascular risk is a priority. PMID- 1603763 TI - Introduction. HIV and AIDS. Challenges and rewards for primary care physicians. PMID- 1603764 TI - Essential HIV/AIDS facts. What you need to know in 1992. AB - The fast pace of HIV/AIDS research and the wide spectrum of issues involved can be intimidating for busy primary care physicians who see HIV-infected patients infrequently. The information covered in this article is intended to form a core that should be a part of all physicians' medical knowledge today. PMID- 1603765 TI - HIV worldwide. What has happened? What has changed? AB - The human immunodeficiency virus (HIV) has resulted in a worldwide pandemic of infection. By 1991 more than 350,000 AIDS cases had been reported to the World Health Organization, but it is estimated that there are now more than 10 million people infected worldwide. HIV can rapidly spread in new populations: The pandemic is composed of multiple smaller epidemics. In the United States, it is estimated that over a million people are infected with HIV. Methods of estimating this number include extrapolation from the number of reported cases of AIDS, use of mathematical modeling and back-calculation, and seroprevalence surveys. Minorities continue to be overrepresented among those infected, and the prevalence of HIV in women is increasing. In serosurveys, it has been found that as HIV prevalence rates rise, the ratio of infected males to infected females approaches 1:1, suggesting an increased proportion of hetero-sexual transmission. HIV is now variably present but widespread across the United States. The epidemiology of HIV-related illnesses is also changing, as can be seen with current patterns of tuberculosis. HIV continues to be an increasingly complex and dangerous global burden. PMID- 1603766 TI - [Marital disharmony of the parents and child development in infancy and early childhood]. AB - As part of a prospective study currently being conducted in the Mannheim Heidelberg region of Germany on the neuropsychiatric development of 362 children born at varying degrees of organic and psychosocial risk, the effect of marital discord on the cognitive and social-emotional development of 315 children born into two-parent households was investigated. Both the children and the quality of the parental relationship were evaluated when the children were 3 months and two years of age. Assessment of the children included performance on the Bayley Scales of Infant Development, observed and reported temperament characteristics and measures of infant and child psychopathology. Evaluation of the relationship was based on pertinent information provided by the parents about their marriage within a standardized interviews as well as on the basis of a questionnaire. Results show that marital discord at 3 months does not effect child performance at 3 months, nor at 24 months. Marital discord at 2 years does affect the emotional well-being of the two-year-old i.e. is accompanied by a significant rise in psychopathological symptoms. When the effect of the stability of marital strife from the first assessment to the second was studied a significant increase in behavior problems and decrease in Bayley performance was found in the group of children whose parents' marital situation had deteriorated and failed in the meantime but surprisingly not in the group with chronic discordant relationships. Conversely, poor child performance and emotional adjustment improved with a positive change in the parental relationships. An increase, although not significant, was also found among the children whose parents' marriage had deteriorated but had not lead to separation. PMID- 1603767 TI - [Ego disturbances in mentally retarded children--beginnings of an understanding]. AB - The disturbed person has a structured, subjective logical inner-world, but we fail in understanding, because our mentality structures the world in a way, which is not analogue with that of the disturbed. It's required therefore first the reflexion of our own limitation and second the search for sense in the disturbedness of the other. This new and enhanced form of understanding is a joint starting-point of all workers in psychology and will remove the bounds between theory and practice and between theory and lack of understanding. PMID- 1603768 TI - [Psychosocial aspects of premature birth of a child--a status assessment]. AB - This article describes psychosocial dimensions of premature birth. This review follows the course of pregnancy, birth and perinatal period in hospital and at home in characteristic features. Being in neonatal intensive care units, the baby's sensomotoric and interaction skills have to be trained by medical and nursing staff. The staff assists and instructs parents in special care and handling procedures. There are in the literature numerous differentiated empirical reports, but usually these are focused on child, or family or staff. The authors emphasize that there is a lack of research considering process and interactions between the different groups. Psychosocial data concerning "new" specific subgroups among premature infants resulting from medical and technological advances in the last years are lacking. PMID- 1603769 TI - [Development of communicative competence in infancy]. AB - An introductory review about developmental psychological issues of the process of infant language acquisition in the first year of life is presented with a short discussion on its relation with child psychopathology. Instead of a discontinuity a continuity seems to exist from the infant initial communicative signals, such as gesture, facial expression and preverbal vocalizations, to the best known milestones of the infant language development. The particular aspects concerning the origin of a symbolic code--the origin of language--are briefly presented. PMID- 1603770 TI - [Granulomatous hypophysitis. Report of three cases and review of the literature]. PMID- 1603771 TI - [Sarcoid granulomatosis after many years of exposure to zirconium, "zirconium lung"]. PMID- 1603772 TI - [Esthesioneurogenic tumor in a dog]. PMID- 1603773 TI - [Mesonephroid hyperplasia of the uterine cervix]. PMID- 1603774 TI - [The value of immunohistochemistry in routine histologic diagnosis of metastases of unknown primary tumors]. PMID- 1603775 TI - [Analysis of congenital angiocardiopathies in an autopsy sample of the Pathologic Institute of the Saarland University 1947-1986]. PMID- 1603776 TI - [Hermansky-Pudlak syndrome with pulmonary fibrosis in two brothers]. PMID- 1603777 TI - [Differential diagnostic problems in fibrosing mediastinitis]. PMID- 1603778 TI - [HEA125 and BerEP4 in neuro-oncologic differential diagnosis]. PMID- 1603779 TI - [Arteriovenous differences in the state of the hemostasis system of patients with pulmonary tuberculosis]. AB - The process of intravascular hemocoagulation in patients with active pulmonary tuberculosis proved to occur both in the microcirculatory bed of systemic circulation and within the organs, in the microvasculature of the affected lung. Enhanced antithrombin III uptake during intravascular hemocoagulation occurring within the organs in the patients and its insufficient reproduction in the vascular bed of the pulmonary circulation are the most important mechanisms responsible for imbalance in the hemostatic system. It has been concluded that the effective influence on the main focus of a specific lesion during the preoperative management of patients and the improvement of liver function will increase the effectiveness of prevention of thrombohemorrhagic complications in the surgical treatment of pulmonary tuberculosis. PMID- 1603780 TI - [Effectiveness of a liposomal form of rifampicin in the treatment of experimental tuberculosis in mice]. AB - The therapeutic effectiveness of rifampicin as a free form and a component of multilamellar phosphatidylcholine cholesterol liposomes was studied on a model of generalized tuberculosis in BALB/c mice. Rifampicin as a liposomal form was found to have no advantages over its free form. Possible mechanisms of the phenomenon and prospects for using liposomes in the chemotherapy of tuberculosis are discussed. PMID- 1603781 TI - [BCG revaccination of school children in circumstances of low incidence of tuberculosis]. AB - The results of study of a tuberculosis infection course in different conditions and its association with BCG revaccination are presented. The Moscow region was tentatively divided into 3 groups of regions. Children of Group 1 were not given revaccination at 7 and 12 years, those of Group 2 at 12 years and those of group 3 received revaccination according to the routine techniques at 7, 12 and 17 years. BCG revaccination withdrawal caused no increase in tuberculosis morbidity and tuberculin sensitivity. Tuberculosis detections were unassociated with the frequency of previous BCG revaccination. PMID- 1603782 TI - [Revaccination of schoolchildren with BCG-M vaccine and use of a new model of BI 19 jet injector]. AB - A comparative analysis of the effectiveness of revaccination of 1595 schoolchildren with the BCG and BCG-M vaccine is given in relation to the method of vaccine administration and revaccination frequency (1st revaccination was given in the 1st and 2nd in the ninth form). Both vaccines were found to be equally effective both in the development of a postvaccination skin sign and postvaccination allergy. The method of BCG vaccine administration (with a jet injector and needle syringe) had no essential influence on the revaccination effect. The advantage of a new BI-19 jet injector used for tuberculin diagnosis consisted in that there was no need to adjust the results of tuberculin diagnosis as was the case with a previous BI-IM jet injector. PMID- 1603783 TI - [Formation of dispensary contingents of adults with cured pulmonary tuberculosis and their follow-up]. AB - The case histories of 5394 subjects who were registered in a number of Moscow. Tuberculosis Dispensaries during 1976-1988 were studied. These subjects belonged to groups III-VII and were earlier struck off the register. In Formation of groups III-VII of dispensary registry, there is an early establishment of the clinical recovery of pulmonary tuberculosis, therefore the patients with an uncured or progressive process are included in these groups. Reactivation of actually cured tuberculosis was found only in 70.7% of the subjects and the rest had an active process which has been misinterpreted as cured or as hyperdiagnosed reactivation. The main causes of the early establishment of clinical recovery, failure to establish the onset of reactivation and its hyperdiagnosis were the inadequate examination of X-ray positive subjects before their enrollment in III VII groups, during follow-ups and striking-off, as well as errors in dispensary tactics, i. e. inadequate pre-enrollment in the O-group and diagnostic treatment. Tests for M. tuberculosis by repeated inoculation and tomography should be used in all cases in establishing clinical cure, forming Groups III-VII, following up the patients, and striking off. PMID- 1603784 TI - [State of nonpulmonary tuberculosis care in West Siberia]. AB - Basic epidemiologic parameters in relation to extrapulmonary tuberculosis were analysed in 6 regions of West Siberia as well as the state of the material technical base of extrapulmonary service in these areas. Despite a general reduction of the revealed incidence and morbidity of extrapulmonary tuberculosis, the true incidence persists at a high level with predominance of advanced forms of the process. One of the causes of this situation is insufficient material technical support of extrapulmonary tuberculosis service in West Siberia. PMID- 1603785 TI - [New surgical tactics in the treatment of patients with complicated tuberculosis of the lungs and pleura]. AB - Stepwise surgical tactics by using transsternal transepicardial preocclusion of the main bronchus and lung root vessels, opening of the empyema cavity and pneumotomy has been proposed to treat patients with progressive fibrocavernous tuberculosis complicated by pneumothorax and pleural empyema and extended into the thoracic wall. After 1.5-2 months the main stage of the operation, pleuropulmonectomy, is performed. Among the 25 patients operated on, the clinical effect was achieved in 15, 5 patients continued to take treatment, 5 patients died. The first results show that active care may be delivered to patients with complicated pulmonary and pleural tuberculosis who have recently had no hope to be recovered and the process be steady. PMID- 1603786 TI - [Magnetic resonance tomography in the diagnosis of tuberculous spondylitis]. AB - The examination included 35 patients with clinical and X-ray signs of tuberculous spondylitis. Magnetic resonance tomography (MRT) was performed on a Maganview apparatus (Finland). MRT helped to diagnose an active process in 5 patients. The most manifested changes were found on T2-suspended tomograms to indicate an inflammatory reaction of the bone marrow. MRT was effective in detecting bone marrow compression, its early atrophy, hydromyelia and postoperative changes. MRT can obviously fully replace pneumomyelography and myelography with contrast substances. PMID- 1603787 TI - [Precise resection of the lung using neodymium YAG laser]. AB - Radiation of the neodymium YAG laser in the noncontact and contact regimens with a sapphire tips was employed for maximally sparing removal of different pathological formations from the lung. The laser was used for dissection and coagulation of lung tissue to obtain reliable air- and hemostasis of the wound surface of the lung. A total of 29 patients were operated on. A noncontact photocoagulation regimen produces a strong coagulation layer that sustains the intrapulmonary pressure up to 40 cm H2O. Preliminary ligation of large bronchial branches in the resection zone is obligatory. The postoperative period showed a rapid restoration of lung tissue structure at the site of intervention. PMID- 1603788 TI - [Mechanical properties of the lungs and capillary blood flow in patients with cavernous tuberculosis before and after partial resection]. AB - The results of the study of pulmonary ventilation function, respiratory biomechanics and capillary blood flow in 16 patients with cavernous tuberculosis before and after partial resections are given. An obstructive component due to the inflammatory changes in the bronchial tree was found to underlie moderate impairments in pulmonary mechanical properties. The capillary blood flow depends on the magnitude of secondary changes in lung tissue. Partial resections lead to deterioration of elastic properties of the lungs in combination with reduced capillary network. Recovered functional parameters in the long-term period of the follow-up confirms that it is expedient to use partial resection in the early stage of a combined treatment of patients with cavernous pulmonary tuberculosis. PMID- 1603789 TI - [Cytograms of bronchoalveolar lavage fluid in disseminated lung processes and their correlation with cytomorphological pattern of biopsy specimens]. AB - Examination included the findings of 141 patients with various granulomatous pulmonary diseases: tuberculosis (26), sarcoidosis (100) and exogenous-allergic alveolitis (15). The biopsy specimens were divided into 3 groups depending on the nature of changes: (1) the presence of epithelioid-cellular granulomas (EG) (80); (2) fibrous changes (47); (3) caseous detritus (14). Patients with EG in the biopsy specimens had mean lymphocytosis of 41.3 +/- 6% in bronchoalveolar washings (BAW) in all granulomatous diseases. Correlation between the cellular BAW composition and cytomorphologic pattern of the biopsy specimens has revealed more stable links between the presence of EG in biopsy specimens and lymphocytosis in BAW in tuberculosis, sarcoidosis and endogenous-allergic alveolitis. Tuberculosis patients, in addition to lymphocytosis in BAW, have increased neutrophils which depended on the degree of exudative-necrotic reactions that accompanied the formation of tuberculous granulomas. Patients with fibrous changes in the biopsy specimens had varying increases in neutrophil counts in BAW (11.7 +/- 2.3%). The lymphocyte count in BAW in the presence of caseous detritus in the biopsy specimens in tuberculosis in the absence of granulomas decreased (47.8 +/- 7.5 and 12.5 +/- 3.3%) and the neutrophil count increased (20.6 +/- 6.3 and 24.9 +/- 6.9%). PMID- 1603790 TI - [Chemoprophylaxis of tuberculosis (lecture)]. PMID- 1603791 TI - [Use of the mathematical method in prognostication of effectiveness of the treatment of recurrences in pulmonary tuberculosis]. PMID- 1603792 TI - [Prognostication of the dynamics of metatuberculous pulmonary sclerosis]. PMID- 1603793 TI - [Development of laboratory investigation methods in phthisio-pulmonology (summary of activities of the Central Research Institute of Tuberculosis, USSR Ministry of Health, during the twelfth 5-year plan of the laboratory section of the All-Union program 0.69.08)]. AB - Comprehensive laboratory studies were performed to develop and introduce new techniques for examining patients with respiratory tuberculosis and some other pulmonary diseases. The techniques should improve and develop the immunologic and bacteriological diagnosis of tuberculosis, sarcoidosis, various exogenous allergic alveolitis and nonspecific inflammatory (microbial and mycotic) pulmonary diseases. Some of the methods were elaborated for morphological verification of sarcoidosis, alveolitis and rare pulmonary diseases. Radioimmuno , enzyme immuno-, and other assays for the activity of various enzymes, as well as biochemical methods for assessing the superficial properties of individual cellular elements have found application in performing biochemical studies in pulmonary tuberculosis and non-specific diseases. Immunologic, bacteriological, cytologic and biochemical methods of study have been adjusted to examine the amount of bronchoalveolar washings in patients with different pulmonary diseases. PMID- 1603794 TI - [Effects of low-intensity garnet laser irradiation on microorganisms and wounds]. AB - The influence of low-intensity garnet laser radiation a wavelength of 0.53 microns (green spectrum) on Mycobacterium tuberculosis (MT), nonspecific microflora and regeneration of aseptic and purulent wounds has been studied experimentally for the first time. Irradiation of MT and nonspecific microflora inoculations has shown that this type of laser radiation fails to stimulate growth of MT and nonspecific microflora and has an inhibiting action on MT manifested by delayed MT growth, a lower number of dimensions of the growth colonies as compared to those of the control inoculations and has a bacteriostatic action on micrococci and Neisseria organisms. Influence of this type of laser on the aseptic and purulent wounds in 50 guinea pigs has revealed a more rapid regeneration of aseptic wounds (by 3-4 days) as compared to the control. PMID- 1603795 TI - [Carcinomatous angiitis of the lungs simulating disseminated tuberculosis in occult gastric cancer]. PMID- 1603796 TI - [Associated localization of Kaposi's sarcoma in a patient with AIDS]. PMID- 1603797 TI - [Biochemical mechanisms of neurotoxic reactions to antibacterial preparations in patients with pulmonary tuberculosis]. AB - Examination comprising the electrophysiologic method and study of the biochemical parameters of the antioxidant/lipid peroxidation system and metabolism of biologic amines in 163 patients with infiltrative pulmonary tuberculosis has revealed a clear interaction existing between the functional changes of the CNS state, the state of antioxidative defense (alpha-tocopherol) and serotonin. This allows an assumption that the antioxidant/lipid peroxidation system and serotoninergic system actively participate in the pathogenesis of development of neurotoxic reactions to antibacterial preparations in the clinical picture of tuberculosis. PMID- 1603798 TI - Redesigning the DNA-binding specificity of a zinc finger protein: a data base guided approach. AB - A peptide corresponding to the three zinc finger domains of the human transcription factor Sp1 has been expressed and found to bind a consensus Sp1 binding site with the sequence 5'-GGGGCGGGG-3'. Examination of the amino acid distributions within a large zinc finger sequence data base and chemical arguments suggested that a particular Arg to Gln sequence change might convert binding specificity to 5'-GGGGCAGGG-3'. Experimental tests of this hypothesis revealed that such a change could be induced only when two other sequence changes, deduced from examination of sequence correlations, were made as well. These results provide the most direct information to date about how zinc finger proteins might recognize adenine-containing binding sites and bear on the existence and nature of any code between zinc finger protein and binding site sequences. PMID- 1603799 TI - Protein design on computers. Five new proteins: Shpilka, Grendel, Fingerclasp, Leather, and Aida. AB - What is the current state of the art in protein design? This question was approached in a recent two-week protein design workshop sponsored by EMBO and held at the EMBL in Heidelberg. The goals were to test available design tools and to explore new design strategies. Five novel proteins were designed: Shpilka, a sandwich of two four-stranded beta-sheets, a scaffold on which to explore variations in loop topology; Grendel, a four-helical membrane anchor, ready for fusion to water-soluble functional domains; Finger-clasp, a dimer of interdigitating beta-beta-alpha units, the simplest variant of the "handshake" structural class; Aida, an antibody binding surface intended to be specific for flavodoxin; Leather--a minimal NAD binding domain, extracted from a larger protein. Each design is available as a set of three-dimensional coordinates, the corresponding amino acid sequence and a set of analytical results. The designs are placed in the public domain for scrutiny, improvement, and possible experimental verification. PMID- 1603800 TI - Conformational analysis of a 12-residue analogue of mastoparan and of mastoparan X. AB - We have investigated the conformational properties of a truncated analogue of mastoparan and of mastoparan X, both peptides from wasp venom. The electrostatically driven Monte Carlo method was used to explore the conformational space of these short peptides. The initial conformations used in this study, mainly random ones, led to alpha-helical conformations. The alpha helical conformations thus found exhibit an amphipathic character. These results are in accord with experimental data from NMR and CD spectroscopy. PMID- 1603801 TI - Electrostatic fields at the active site of ribulose-1,5-bisphosphate carboxylase. AB - A macroscopic approach has been employed to calculate the electrostatic potential field of nonactivated ribulose-1,5-bisphosphate carboxylase and of some complexes of the enzyme with activator and substrate. The overall electrostatic field of the L2-type enzyme from the photosynthetic bacterium Rhodospirillum rubrum shows that the core of the dimer, consisting of the two C-terminal domains, has a predominantly positive potential. These domains provide the binding sites for the negatively charged phosphate groups of the substrate. The two N-terminal domains have mainly negative potential. At the active site situated between the C terminal domain of one subunit and the N-terminal domain of the second subunit, a large potential gradient at the substrate binding site is found. This might be important for polarization of chemical bonds of the substrate and the movement of protons during catalysis. The immediate surroundings of the activator lysine, K191, provide a positive potential area which might cause the pK value for this residue to be lowered. This observation suggests that the electrostatic field at the active site is responsible for the specific carbamylation of the epsilon amino group of this lysine side chain during activation. Activation causes a shift in the electrostatic potential at the position of K166 to more positive values, which is reflected in the unusually low pK of K166 in the activated enzyme species. The overall shape of the electrostatic potential field in the L2 building block of the L8S8-type Rubisco from spinach is, despite only 30% amino acid homology for the L-chains, strikingly similar to that of the L2-type Rubisco from Rhodospirillum rubrum. A significant difference between the two species is that the potential is in general more positive in the higher plant Rubisco. In particular, the second phosphate binding site has a considerably more positive potential, which might be responsible for the higher affinity for the substrate of L8S8-type enzymes. The higher potential at this site might be due to two remote histidine residues, which are conserved in the plant enzymes. PMID- 1603802 TI - Characterization of a putative calcium-binding site in tobacco mosaic virus. AB - Lead has been used as a substitute for calcium binding to tobacco mosaic virus (TMV). The high atomic number of lead has allowed us to use difference maps from X-ray fiber diffraction data to characterize a calcium-binding site in the virus. The metal ligands are slightly different from those previously believed to bind calcium to TMV, although the binding site is very close to one previously described. Two acetate groups are also bound to the lead atom. There is no significant backbone conformational change in the protein as a result of metal binding; the binding is accomplished by means of relatively small movements in amino acid side chains. PMID- 1603803 TI - Crystal structure of the binary complex of pig muscle phosphoglycerate kinase and its substrate 3-phospho-D-glycerate. AB - Pig muscle phosphoglycerate kinase has been crystallized from polyethyleneglycol in the presence of its substrate 3-phospho-D-glycerate (3-PG) and the structure has been determined at 2.0 A resolution. The structure was solved using the known structure of the substrate-free horse muscle enzyme and has been refined to a crystallographic R-factor of 21.5%. 3-Phospho-D-glycerate is bound to the N domain of the enzyme through a network of hydrogen bonds to a cluster of basic amino acid residues and by electrostatic interactions between the negatively charged phosphate and these basic protein side chains. This binding site is in good agreement with earlier proposals [Banks et al., Nature (London) 279:773-777, 1979]. The phosphate oxygen atoms are hydrogen bonded to His-62, Arg-65, Arg-122, and Arg-170. The 2-hydroxyl group, which defines the D-isomer of 3PG, is hydrogen bonded to Asp-23 and Asn-25. The carboxyl group of 3-PG points away from the N domain towards the C-domain and is hydrogen bonded via a water molecule to main chain nitrogen atoms of helix-14. The present structure of the 3-PG-bound pig muscle enzyme is compared with the structure of the substrate-free horse enzyme. Major changes include an ordering of helix-13 and a domain movement, which brings the N-domain closer to the ATP-binding C-domain. This domain movement consists of a 7.7 degree rotation, which is less than previously estimated for the ternary complex. Local changes close to the 3-PG binding site include an ordering of Arg 65 and a shift of helix-5. PMID- 1603804 TI - Correlations of atomic movements in lysozyme crystals. AB - Diffuse scattering data have been collected on two crystal forms of lysozyme, tetragonal and triclinic, using synchrotron radiation. The observed diffraction patterns were simulated using an exact theory for simple model crystals which relates the diffuse scattering intensity distribution to the amplitudes and correlations of atomic movements. Although the mean square displacements in the tetragonal form are twice that in the triclinic crystal, the predominant component of atomic movement in both crystals is accounted for by short-range coupled motions where displacement correlations decay exponentially as a function of atomic separation, with a relaxation distance of approximately 6 A. Lattice coupled movements with a correlation distance approximately 50 A account for only about 5-10% of the total atomic mean square displacements in the protein crystals. The results contradict various presumptions that the disorder in protein crystals can be modeled predominantly by elastic vibrations or rigid body movements. PMID- 1603805 TI - Domain flexibility in aspartic proteinases. AB - Comparison of the three-dimensional structures of native endothiapepsin (EC 3.4.23.6) and 15 endothiapepsin oligopeptide inhibitor complexes defined at high resolution by X-ray crystallography shows that endothiapepsin exists in two forms differing in the relative orientation of a domain comprising residues 190-302. There are relatively few interactions between the two parts of the enzyme; consequently, they can move as separate rigid bodies. A translational, librational, and screw analysis of the thermal parameters of endothiapepsin also supports a model in which the two parts can move relative to each other. In the comparison of different aspartic proteinases, the rms values are reduced by up to 47% when the two parts of the structure are superposed independently. This justifies description of the differences, including those between pepsinogen and pepsin (EC 3.4.34.1), as a rigid movement of one part relative to another although considerable distortions within the domains also occur. The consequence of the rigid body movement is a change in the shape of the active site cleft that is largest around the S3 pocket. This is associated with a different position and conformation of the inhibitors that are bound to the two endothiapepsin forms. The relevance of these observations to a model of the hydrolysis by aspartic proteinases is briefly discussed. PMID- 1603806 TI - Folding of RNase T1 is decelerated by a specific tertiary contact in a folding intermediate. AB - The replacement of tryptophan 59 of ribonuclease T1 by a tyrosine residue does not change the stability of the protein. However, it leads to a strong acceleration of a major, proline-limited reaction that is unusually slow in the refolding of the wild-type protein. The distribution of fast- and slow-folding species and the kinetic mechanism of slow folding are not changed by the mutation. Trp-59 is in close contact to Pro-39 in native RNase T1 and probably also in an intermediate that forms rapidly during folding. We suggest that this specific interaction interferes with the trans----cis reisomerization of the Tyr 38-Pro-39 bond at the stage of a native-like folding intermediate. The steric hindrance is abolished either by changing Trp-59 to a less bulky residue, such as tyrosine, or, by a destabilization of folding intermediates at increased concentrations of denaturant. Under such conditions folding of the wild-type protein and of the W59Y variant no longer differ. These results provide strong support for the proposal that trans----cis isomerization of Pro-39 is responsible for the major, very slow refolding reaction of RNase T1. They also indicate that specific tertiary interactions in folding intermediates do exist, but do not necessarily facilitate folding. They can have adverse effects and decelerate rate limiting steps by trapping partially folded structures. PMID- 1603807 TI - Integrity of refolded and reoxidized gelatin-binding fragments of fibronectin. AB - The gelatin-binding region of fibronectin is easily isolated as a stable and functional 42-kDa fragment (42-kDa GBF) containing four type I "finger" modules and two type II "kringle-like" modules arranged in the order I6-II1-II2-I7-I8-I9, where the numbers designate the order of these modules in each of the two polypeptide chains. Each module forms an independently folded domain stabilized by two disulfide bonds. Reduction of disulfides caused large changes in the intrinsic fluorescence and abolished the gelatin-binding activity of 42-kDa GBF and two nonoverlapping gelatin-binding subfragments, 30-kDa GBF (I6-II1-II2-I7) and 21-kDa GBF (I8-I9). However, high yields of active material could be regenerated, without diluting the protein, by dialysis into GdmCl followed by slow overnight removal of GdmCl while maintaining the redox potential with a mixture of oxidized and reduced glutathione. Fluorescence spectroscopic analysis indicated that the tertiary structure and thermodynamic stability of the refolded fragments were similar to those of the originals. The refolded fragments were quantitatively indistinguishable from the originals with respect to their dissociation constants for binding to a fluorescent-labeled collagen fragment. The results suggest that all or most of the cystines, a total of 24 in 42-kDa GBF, are correctly paired in the refolded products and that the tertiary structure was completely recovered. The fact that the 30- and 21-kDa fragments bind with a similar affinity proves the existence of at least two nonoverlapping sites in 42-kDa GBF that recognize gelatin. PMID- 1603808 TI - Molecular dynamics of HIV-1 protease. AB - Molecular dynamics simulations have been carried out based on the GROMOS force field on the aspartyl protease (PR) of the human immunodeficiency virus HIV-1. The principal simulation treats the HIV-1 PR dimer and 6990 water molecules in a hexagonal prism cell under periodic boundary conditions and was carried out for a trajectory of 100 psec. Corresponding in vacuo simulations, i.e., treating the isolated protein without solvent, were carried out to study the influence of solvent on the simulation. The results indicate that including waters explicitly in the simulation results in a model considerably closer to the crystal structure than when solvent is neglected. Detailed conformational and helicoidal analysis was performed on the solvated form to determine the exact nature of the dynamical model and the exact points of agreement and disagreement with the crystal structure. The calculated dynamical model was further elucidated by means of studies of the time evolution of the cross-correlation coefficients for atomic displacements of the atoms comprising the protein backbone. The cross-correlation analysis revealed significant aspects of structure originating uniquely in the dynamical motions of the molecule. In particular, an unanticipated through-space, domain-domain correlation was found between the mobile flap region covering the active site and a remote regions of the structure, which collectively act somewhat like a molecular cantilever. The significance of these results is discussed with respect to the inactivation of the protease by site-specific mutagenesis, and in the design of inhibitors. PMID- 1603809 TI - Structures of complexes of rhizopuspepsin with pepstatin and other statine containing inhibitors. AB - The three-dimensional structures of the complexes of the aspartic proteinase from Rhizopus chinensis (Rhizopuspepsin, EC 3.4.23.6) with pepstatin and two pepstatin like peptide inhibitors of renin have been determined by X-ray diffraction methods and refined by restrained least-squares procedures. The inhibitors adopt an extended conformation and lie in the deep groove located between the two domains of the enzyme. Inhibitor binding is accompanied by a conformational change at the "flap," a beta-hairpin loop region, that projects over the binding cleft and closes down over the inhibitor, excluding water molecules from the vicinity of the scissile bond. The hydroxyl group of the central statyl residue of the inhibitors replaces the water molecule found between the two active aspartates, Asp-35 and Asp-218, in the native structure. The refined structures provide additional data to define the specific subsites of the enzyme and also show a system of hydrogen bonding to the inhibitor backbone similar to that observed for a reduced inhibitor. PMID- 1603810 TI - A multiple-start Monte Carlo docking method. AB - We present a method to search for possible binding modes of molecular fragments at a specific site of a potential drug target of known structure. Our method is based on a Monte Carlo (MC) algorithm applied to the translational and rotational degrees of freedom of the probe fragment. Starting from a randomly generated initial configuration, favorable binding modes are generated using a two-step process. An MC run is first performed in which the energy in the Metropolis algorithm is substituted by a score function that measures the average distance of the probe to the target surface. This has the effect of making buried probes move toward the target surface and also allows enhanced sampling of deep pockets. In a second MC run, a pairwise atom potential function is used, and the temperature parameter is slowly lowered during the run (Simulated Annealing). We repeat this procedure starting from a large number of different randomly generated initial configurations in order to find all energetically favorable docking modes in a specified region around the target. We test this method using two inhibitor-receptor systems: Streptomyces griseus proteinase B in complex with the third domain of the ovomucoid inhibitor from turkey, and dihydrofolate reductase from E. coli in complex with methotrexate. The method could consistently reproduce the complex found in the crystal structure searching from random initial positions in cubes ranging from 25 A to 50 A about the binding site. In the case of SGPB, we were also successful in docking to the native structure. In addition, we were successful in docking small probes in a search that included the entire protein surface. PMID- 1603811 TI - Monte Carlo docking of oligopeptides to proteins. AB - A new two-step procedure has been developed for the docking of flexible oligopeptide chains of unknown conformation to static proteins of known structure. In the first step positions and conformations are sampled and the association energy minimized starting from an approximate preselected docking position. The resulting conformations are further optimized in the second step by a Metropolis Monte Carlo minimization, which optimizes each of these structures. The method has been tested on the HIV-1 aspartic proteinase complex with an inhibitor, whose crystallographic structure is known at 2.3 A resolution. Furthermore, the application of this method to the docking of the hendecapeptide 58-68 of the influenza A virus matrix protein to the HLA-A2 molecule produced results which are in agreement with experimental observations in identifying side chains critical for T cell recognition and residues responsible of MHC protein binding. PMID- 1603812 TI - Common features of the conformations of antigen-binding loops in immunoglobulins and application to modeling loop conformations. AB - Using database screening techniques we have examined the relationship between antigen-binding loops in immunoglobulins, and regions of similar conformation in other protein families. The conformations of most antigen-binding loops are not unique to immunoglobulins. But in many cases, the geometrical relationship between the loop and the peptides flanking it differs between the immunoglobulins and other structures with the same loop. We assess model building by data base screening, compared with that based on canonical structures. PMID- 1603813 TI - Molecular modeling of the amphipathic helices of the plasma apolipoproteins. AB - In this paper we propose a classification of the amphipathic helical repeats occurring in the plasma apolipoprotein sequences. It is based upon the calculation of the molecular hydrophobicity potential around the helical segments. The repeats were identified using a new autocorrelation matrix, based upon similarities of hydrophobic and hydrophilic properties of the amino acid residues within the apolipoprotein sequences. The helices were constructed by molecular modeling, the molecular hydrophobicity potential was calculated, and isopotential contour lines drawn around the helices yielded a three-dimensional visualization of the hydrophobicity potential. Two classes of apolipoproteins could be differentiated by comparing the hydrophobic angles obtained by projection of the isopotential contour lines on a plane perpendicular to the long axis of the helix. The isopotential contour lines around apo AI, AIV, and E are more hydrophilic than hydrophobic, whereas they are of similar intensity for apo AII, CI, and CIII. In both cases discoidal lipid-protein complexes are generated, with the amphipathic helices around the edge of the lipid core. The long axis of the helices is oriented parallel to the phospholipid acyl chains and the hydrophilic side of the helix toward the aqueous phase. As a result of the differences in hydrophobicity potential, the contact between the hydrophobic side of the helices and the phospholipid acyl chains is larger for apo AII, CI, and CIII than for the other apolipoproteins. This might account for the greater stability of the discoidal complexes generated between phospholipids and these apoproteins. PMID- 1603814 TI - Detection of native-like models for amino acid sequences of unknown three dimensional structure in a data base of known protein conformations. AB - We present an approach which can be used to identify native-like folds in a data base of protein conformations in the absence of any sequence homology to proteins in the data base. The method is based on a knowledge-based force field derived from a set of known protein conformations. A given sequence is mounted on all conformations in the data base and the associated energies are calculated. Using several conformations and sequences from the globin family we show that the native conformation is identified correctly. In fact the resolution of the force field is high enough to discriminate between a native fold and several closely related conformations. We then apply the procedure to several globins of known sequence but unknown three dimensional structure. The homology of these sequences to globins of known structures in the data base ranges from 49 to 17%. With one exception we find that for all globin sequences one of the known globin folds is identified as the most favorable conformation. These results are obtained using a force field derived from a data base devoid of globins of known structure. We briefly discuss useful applications in protein structural research and future development of our approach. PMID- 1603815 TI - Monthly prostaglandin bibliography prepared by the University of Sheffield Biomedical Information Service. PMID- 1603816 TI - Potential role of prostaglandins and leukotrienes in multiple sclerosis and experimental allergic encephalomyelitis. PMID- 1603817 TI - Characterization of monoclonal antibodies against human leukocyte 5-lipoxygenase. AB - Four mouse monoclonal IgG1 antibody-producing cell lines (5LO-1, 5LO-2, 5LO-3, 5LO-4), produced against highly purified human leukocyte 5-lipoxygenase have been characterized. The monoclonal antibodies produced by these cell lines exhibited differential reactivity against 5-lipoxygenase as determined by ELISA and immunoprecipitation analyses. Monoclonal antibodies 5LO-2 and 5LO-3 inhibited the activity of recombinant human leukocyte 5-lipoxygenase in a dose-dependent manner. This inhibition was selective for 5-lipoxygenase activity since these monoclonal antibodies did not inhibit human leukocyte 15-lipoxygenase or porcine leukocyte 12-lipoxygenase. PMID- 1603818 TI - Misoprostol therapy following trinitrobenzene sulfonic acid-induced colitis accelerates healing. AB - Prostaglandins have been demonstrated to have a mucosal protective effect when administered prior to the experimental induction of colitis in animals. We here determined whether prostaglandins would have a beneficial therapeutic effect when administered after colitis had been established. Diffuse, chronic, trinitrobenzene sulfonic acid-induced colitis was established in rats, and misoprostol was administered daily for up to 10 days following the induction of colitis. The effects of misoprostol therapy were compared to those obtained by treatment with 5-aminosalicylic acid and betamethasone. Misoprostol therapy following trinitrobenzene sulfonic acid-induced colitis accelerated colonic healing, as measured in terms of macroscopic ulceration area and fluid absorption, whereas 5-aminosalicylic acid and betamethasone therapy did not. Ileal fluid absorption impairment was repaired by betamethasone but not by misoprostol or 5-aminosalicylic acid therapy. PMID- 1603819 TI - Essential fatty acids are not required for wound healing. AB - Rats with essential fatty acid deficiency (EFAD) exhibit mild body growth retardation, diminished leukocyte influx in certain models of inflammation, and skin lesions characterized by ulceration, thinning and decreased pigmentation. In the present study we examined the role of EFAD in cutaneous wound healing, a process in which the inflammatory response and the macrophage play a central role. We reproduced the EFAD condition in Lewis rats (n = 35), and examined its effects in wound healing using the paired rat surgical incision model. Rats were compared with weight-matched controls, receiving standard chow diet. Skin samples harvested at days 5, 7, 14 and 21 post-wounding were evaluated for tensiometry and histology. EFAD rats exhibited all the characteristics of this condition, and the typical alteration of liver lipids. Skin samples harvested at different days post-wounding did not show difference in maximal breaking strength when compared to weight-matched controls. Histological evaluation of skin samples showed no difference in the cellular inflammatory infiltration in either EFAD rats or in weight-matched controls. Immunohistochemical studies revealed no difference in the influx of macrophages in the different groups of rats. Fatty acid supplementation of EFAD rats (n = 7), successfully reversed the EFAD state as assessed by the macroscopic skin and liver changes and liver fatty acid content, without modifying either tensile strength or cellular inflammatory infiltration. Our results suggest that EFAD does not alter the normal course of the cutaneous wound repair in rats, despite all the cutaneous alterations produced by this condition. We conclude that essential fatty acids (EFAs) are not essential for cutaneous wound repair. PMID- 1603820 TI - Inhibition of platelet activation and endothelial cell injury by polyphenolic compounds isolated from Lonicera japonica Thunb. AB - Effects of the polyphenolic compounds isolated from Lonicera japonica Thunb on platelet aggregation, platelet thromboxane biosynthesis and hydrogen peroxide induced endothelial cell injury were studied. With regard to the inhibitory effect on human platelet aggregation, methyl caffeate, 3,4-di-O-caffeoylquinic acid and methyl 3,4-di-O-caffeoylquinate had a strong effect. They significantly inhibited the second wave of platelet aggregation induced by ADP. Concerning thromboxane biosynthesis triggered by calcium ionophore A23187 in platelets, methyl caffeate and methyl 3,4-di-O-caffeoylquinate had the most potent inhibitory effect. Methyl 3,4-di-O-caffeoylquinate directly inhibited the conversion of arachidonic acid to thromboxane by platelet microsomes, while methyl caffeate did not have any significant effect on thromboxane biosynthesis in platelet microsomes. In the prevention of hydrogen peroxide-induced endothelial cell injury in culture, protocatechuic acid, methyl caffeate, methyl chlorogenic acid and luteolin were significantly effective. The inhibitory effect on platelet activation and the cytoprotective effect on hydrogen peroxide-induced cell injury may explain the possible role of polyphenolic compounds isolated from Lonicera japonica Thunb in maintaining vascular homeostasis. PMID- 1603821 TI - Eicosanoids production in endometriosis. AB - In order to investigate the production of eicosanoids in human endometrium, myometrium, leiomyoma, adenomyosis, normal ovary, non-endometrial cyst and endometrial cyst, slices of each tissue were incubated. 6-Keto-prostaglandin (PG) F1 alpha, thromboxane (TX) B2, PGF2 alpha and PGE2 concentrations in the incubation medium were measured by direct RIA. 6-Keto-PGF1 alpha production of adenomyosis was significantly higher than that of endometrium, myometrium and leiomyoma, especially in the menstrual phase. The production of eicosanoids in endometrial cyst was significantly higher than that of non-endometrial cyst and normal ovary. These results suggest that endometriosis is associated with increased eicosanoid production in vivo. PMID- 1603822 TI - Eicosanoids in breast cancer patients before and after mastectomy. AB - In 19 patients with a malignant breast tumor, tumor tissue and blood were taken to determine the eicosanoid profile and platelet aggregation. Values were compared with those of patients with benign tumors (n = 4), or undergoing a mammary reduction (n = 7). Postoperatively, blood was taken as well in order to compare pre- and postoperative values. Eicosanoids were measured in peripheral blood monocytes and mammary tissue by means of HPLC; furthermore, TXA2, 6-keto PGF1 alpha, and PGE2 were determined by RIA. Differences in pre- and postoperative values of cancer patients were seen in plasma RIA values: PGE2 and 6-k-PGF1 alpha were significantly higher preoperatively when compared with postoperatively, however, such differences were seen in the control groups as well. Compared to benign tumor or mammary reduction test material the eicosanoid profile of tissue obtained from malignant mammary tumors showed important differences. Except for PGF2 alpha, HHT and 15-HETE no detectable quantities of eicosanoids were found in the non-tumor material, whereas in the malignant tumor material substantial quantities of a number of eicosanoid metabolites were present. Statistically significant correlations could be established between patient/histopathology data and the results of the platelet aggregation assays, e.g. between menopausal status and ADP aggregation; oestrogen receptor (+/-) and collagen and arachidonic acid aggregation, inflammatory cell infiltration score and arachidonic acid aggregation and fibrosis score and ADP aggregation. The results show that eicosanoid synthesis in material from mammary cancer patients is different from that in benign mammary tissue. The implications, in particular, in relation to future prognosis of the patient, remain obscure. PMID- 1603823 TI - Hydrocortisone has a biphasic effect on rat gastric mucosal prostaglandin generation in vivo: inhibition at low doses, stimulation at high doses. AB - To determine the effect of different doses of hydrocortisone sodium succinate (HC) on rat gastric mucosal prostaglandin synthesis, two experiments were performed. In the first experiment, 20 male Lewis rats were divided into 4 groups of 5 rats each and gavaged either with 2 ml of water (control) or different concentrations of HC (10 mg/ml, 100 mg/ml and 500 mg/ml). In the second experiment in a similar design, lower doses of HC were used (water, 0.1 mg/ml, 0.50 mg/ml and 5.0 mg/ml). The rats were killed after 1 h and three 3 x 3 mm pieces of gastric tissue were removed from each rat and incubated for the determination of prostaglandin E2 and 6-keto-prostaglandin F1 alpha accumulation in the medium measured by radioimmunoassay. At low doses HC inhibits rat gastric mucosal prostaglandin synthesis whereas at higher doses HC stimulates it. This biphasic effect of HC on gastric mucosal prostaglandin synthesis may help explain its role in ulcerogenesis. PMID- 1603824 TI - The role of National Board examinations in medical education. PMID- 1603825 TI - The physician in contemporary opera: three divergent approaches to the doctor patient relationship. PMID- 1603826 TI - A history of life expectancy in two developed countries. PMID- 1603827 TI - Malaise in the medical schools. PMID- 1603828 TI - Medical science as magic and metaphor: Thomas Mann's The Magic Mountain. PMID- 1603829 TI - A problem in academic internal medicine: we have taken the teaching out of the teaching hospital. PMID- 1603830 TI - Adventurism in biomedical science: Washington University-Monsanto program in biotechnology. AB - The Washington University-Monsanto relationship has supported innovation in the biological sciences. It has done so in part by making the fence between an industrial and an academic institution more transparent and more easy to cross. A unique means of promoting intellectual adventurism may be lost, however, if this type of relationship is not structured to maximize the likelihood of obtaining products or if products are the only financial benefit that the industrial partner can derive from such interactions (for example other benefits could include governmental R&D tax credits for those relationships that satisfy some minimal criteria for size and/or length of commitment). I hope that this and other forms of industrial-university relationships that encourage discovery by providing institutional support for new ideas will flourish. Whatever their fate, the responsibility for promoting dreams must be shared by all of us: by those who are privileged to have students in their labs, by academic institutions as they seek to define their roles in the next century, by peer review boards, by national science policymakers, and perhaps by industry. I have presented the Washington University-Monsanto collaboration not as a complete answer to the question of how to promote intellectual adventurism in the biomedical sciences but rather as a concrete response to a problem that must be clearly articulated, thoroughly examined, and creatively addressed. PMID- 1603831 TI - Abandoning the lecture: curriculum reform in the introduction to clinical medicine. PMID- 1603832 TI - Scientific writing and four contributors. PMID- 1603833 TI - Medical education and the National Boards. PMID- 1603834 TI - Regarding antigay bias. PMID- 1603835 TI - Regarding antigay bias. PMID- 1603836 TI - Revisiting coronary care. PMID- 1603837 TI - Past and present. The family doctor. PMID- 1603838 TI - Western Norwegian medicine: from Hansen to Haukeland. PMID- 1603839 TI - Information for Mandarin tones in the amplitude contour and in brief segments. AB - While the tones of Mandarin are conveyed mainly by the F0 contour, they also differ consistently in duration and in amplitude contour. The contribution of these factors was examined by using signal-correlated noise stimuli, in which natural speech is manipulated so that it has no F0 or formant structure but retains its original amplitude contour and duration. Tones 2, 3 and 4 were perceptible from just the amplitude contour, even when duration was not also a cue. In two further experiments, the location of the critical information for the tones during the course of the syllable was examined by extracting small segments from each part of the original syllable. Tones 2 and 3 were often confused with each other, and segments which did not have much F0 change were most often heard as Tone 1. There were, though, also cases in which a low, unchanging pitch was heard as Tone 3, indicating a partial effect of register even in Mandarin. F0 was positively correlated with amplitude, even when both were computed on a pitch period basis. Taken together, the results show that Mandarin tones are realized in more than just the F0 pattern, that amplitude contours can be used by listeners as cues for tone identification, and that not every portion of the F0 pattern unambiguously indicates the original tone. PMID- 1603840 TI - Declination of supralaryngeal gestures in spoken Italian. AB - Two experiments investigate a weakening of supralaryngeal gestures in an utterance, analogous in some ways to declination of fundamental frequency and amplitude. In one experiment, acoustic measures revealed progressive centralization of stressed /i/, /a/ and /u/ left to right in trisyllabic utterances read by Tuscan subjects. A second experiment, using speakers of a different (Northern) variety of Standard Italian, found reduction in jaw opening for stressed /a/ left to right, but generally failed to replicate a centralization of /i/. This experiment further suggested that the progressive weakening of supralaryngeal gestures is largely a phrase level rather than a word level phenomenon. Both experiments found a different, V-shaped, pattern of opening to be generally characteristic of unstressed syllables. PMID- 1603842 TI - Alternative measures of photosystem II electron transfer inhibition in anthraquinone-treated chloroplasts. AB - We have previously used chlorophyll fluorescence measurements at Fmax conditions (i.e. with Photosystem II electron acceptor QA reduced) to monitor the action of 9,10-anthraquinones on photosynthetic electron transport in plant chloroplasts. The present investigation employs two additional techniques to characterize the extent of electron transport inhibition induced by the addition of substituted anthraquinones to the suspending medium of spinach chloroplasts. Results are presented for spectrophotometric assays of the rate of electron transfer to an exogenous electron acceptor, 2,6-dichloroindophenol (DCIP) and for electrochemical determinations of the rate of oxygen evolution in anthraquinone treated chloroplasts. In general, amino-substituted anthraquinones are ineffective inhibitors, maintaining electron transfer rates to DCIP at levels ranging from 50 to 90% of normal rates and yielding rates of O2 evolution averaging at 70% of the rate in untreated chloroplasts. In contrast, hydroxy substituted anthraquinones efficiently block Photosystem II electron transport, resulting in low rates of DCIP photoreduction ranging from 0 to 20% of normal values and reducing O2 evolution rates to an average of 30% of the rate observed for untreated chloroplasts. Relative rates of DCIP photoreduction for anthraquinone-treated chloroplasts show a strong linear correlation with the reported relative Fmax chlorophyll fluorescence intensities. Relative O2 evolution rates are observed to correlate with the Stern-Volmer fluorescence quenching parameter Ksv. We suggest that slight differences in the extent of inhibitory activity of an anthraquinone as measured by the three techniques are consistent with certain known Photosystem II heterogeneities. The similarities in relative rankings of inhibitory effects for the 9, 10-anthraquinones, however, demonstrate that the three techniques employed (measurements of Fmax chlorophyll fluorescence, DCIP photoreduction rates, and O2 evolution rates) are alternative assays of anthraquinone-induced Photosystem II electron transport inhibition. PMID- 1603841 TI - Inactivation of wild-type and rad mutant Caenorhabditis elegans by 8 methoxypsoralen and near ultraviolet radiation. AB - Survival of wild-type and four radiation-sensitive (rad) mutants of the nematode Caenorhabditis elegans was determined after near-UV irradiation in the presence of 8-methoxypsoralen (8-MOP). Three sets of inactivation profiles were generated for each strain by irradiating synchronous populations of either early embryos, late embryos or first-stage larvae (L1s). Late embryos were consistently the most sensitive. Curiously, none of the four rad mutants were even moderately hypersensitive. Split-dose experiments indicated that DNA-DNA crosslinks were primarily responsible for lethality. Crosslink induction and repair were determined using two different assays. In both cases, little if any repair was observed in wild-type. This lack of repair thus explains why the rad mutants were not hypersensitive to 8-MOP photoinactivation. Since early embryos undergo extensive cell cycling, their resistance to 8-MOP photoinactivation suggests that replication is highly refractory to both monoadducts and crosslinks, as has been demonstrated previously for UV radiation-induced photoproducts (Hartman et al., 1991, Mutat. Res., 255, pp. 163-173). PMID- 1603844 TI - The mechanism of photosensitization in photodynamic therapy: chemiluminescence caused by photosensitization of porphyrins in saline containing human serum albumin. AB - Chemiluminescence (CL) caused by photosensitization of porphyrins in phosphate buffered saline (PBS) solution containing 3% human serum albumin (HSA) was observed for the first time. Irrespective of porphyrins concerned, CL shows a spectrum ranging from 380 to 520 nm with a peak near 450 nm and decays almost single-exponentially with a lifetime of about 15 s. The intensity of CL depends on concentrations of porphyrins and HSA in PBS solution. We have examined a number of porphyrins and observed CL for the compounds with triplet lifetimes longer than 0.1 ms. The appearance and quenching of CL by photosensitization of porphyrin-HSA systems indicate that type II reaction by singlet oxygen occurs significantly in photodynamic therapy resulting in hypoxic regions in environments surrounding the sensitizer. PMID- 1603843 TI - Observations on the synthesis and in vivo photodynamic activity of some benzochlorins. AB - An improved synthesis of benzochlorins is reported. Demetallation of the meso hydroxymethylvinyl derivative of octaethylporphyrin, followed by treatment with sulfuric acid results in cyclization to generate the corresponding octaethylbenzochlorin in high yield. Prolonged treatment with acid generates the sulfonated derivative. These sensitizers were shown to be efficient photodynamic agents in vivo. Animals bearing a transplanted N-[4-(5-nitro-2-furyl)-2 thiazoly]formamide induced urothelial tumor were treated with either the benzochlorin or its sulfonated derivative. Irradiation of tumors 24 h later resulted in a significant tumoricidal effect in a short term assay. We conclude that benzochlorins warrant further examination as potential agents for use in photodynamic therapy. PMID- 1603845 TI - Discrepancies in the measurement of spectral sources. AB - Comparison of spectroradiometric and meter measurements of a series of ultraviolet radiation sources indicates that a wide divergence between readings can occur. We found that with a xenon arc filtered as a solar simulator producing UV-A (320-400 nm) and UV-B (290-320 nm) radiation, the meter can either over- or underestimate the emission of the source when different cut-off filters are used. The most severe the UV-B meter reading, although the UV-A reading can also reading can reading can also be problematic. Meters should be calibrated used to measure. PMID- 1603846 TI - How does photodynamic therapy work? PMID- 1603847 TI - Synthesis and evaluation of 2-diazo-3,3,3-trifluopropanoyl derivatives of colchicine and podophyllotoxin as photoaffinity labels: reactivity, photochemistry, and tubulin binding. AB - Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2-diazo-3,3,3-trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, and N-DTFP-deacetylthiocolchicine was shown to competitively inhibit tubulin-colchicine binding with a Ki of 4-5 microM. The tubulin off-rate of this analog was similar to that of podophyllotoxin, rather than to the relatively irreversibly bound colchicine. Photochemical solvent insertion reactions of the labels were investigated. Radioactive samples of the two most active labels were prepared and used in initial protein-labeling experiments, during which the fractional occupancy of tubulin and extent of covalent incorporation were determined. A rearrangement of DTFP amides was encountered which is relevant to the utility of this moiety for use in synthesis of photoaffinity labels. PMID- 1603848 TI - Fluorescence studies with human epidermal growth factor. AB - Steady-state and time-resolved fluorescence studies have been performed with human epidermal growth factor, a small globular protein having two adjacent tryptophan residues near its C-terminus. Based on the relatively red fluorescence and accessibility to solute quenchers, the two tryptophan residues are found to be exposed to solvent. Anisotropy decay measurements show the dominant depolarizing process to have a sub-nanosecond rotational correlation time indicating the existence of rapid segmental motion of the fluorescing tryptophan residues. From an analysis of the low-temperature excitation anisotropy spectrum of the protein (and in comparison with that of tryptophan, the peptide melittin, and the dipeptide trp-trp), it is concluded that homo-energy transfer and/or exciton interaction occurs between the adjacent tryptophan residues. A thermal transition in the structure of the protein, which is observed by circular dichroism measurements, is not sensed by the steady-state fluorescence of the protein. This result, in conjunction with the anisotropy decay results, indicates that the two tryptophan residues are in a highly flexible C-terminus segment, which is not an integral part of the three-dimensional structure of the protein. Fluorescence measurements with three site-directed mutants also show very little variation. PMID- 1603849 TI - Phototoxic and photochemical properties of sanguinarine. AB - Sanguinarine, a commercial drug exhibiting antimicrobial and antitumor properties, was studied with respect to its basic photochemical characteristics and also with regard to its phototoxicity to mosquito larvae (Aedes atropalpus). Sanguinarine proved to be clearly phototoxic to larvae, with an LD50 of 0.096 mg/mL with near UV exposure as compared with 23.3 mg/mL without. Flash photolysis experiments enabled the study of the triplet state of sanguinarine to be undertaken. Quenching by oxygen occurs with a rate constant of 6 x 10(9) M-1s-1 and time-resolved emission studies indicate that sanguinarine produces a significant amount of singlet oxygen (phi delta = 0.16) as does the isoquinoline alkaloid, berberine (phi delta = 0.25). These values represent the first direct quantitative measurements of photosensitization parameters of these compounds. Additionally, sanguinarine exhibits efficient electron donation properties, undergoing reaction with methyl viologen with a rate constant greater than 10(10) M-1s-1, but is a poor electron acceptor. Phototoxicity of sanguinarine can thus be explained in terms of its photosensitization properties. PMID- 1603850 TI - Photoactivation of hypericin generates singlet oxygen in mitochondria and inhibits succinoxidase. AB - Photosensitized inhibition of mitochondrial succinoxidase by hypericin was measured in vitro and found to be drug-dose, light-dose, and wavelength dependent. Singlet oxygen generation, monitored using the singlet oxygen trap tetramethylethylene, and oxygen consumption in isolated mitochondria sensitized by hypericin were also light-dose and wavelength dependent. Unequivocal evidence for the generation of singlet oxygen was obtained using kinetic isotope ratios of products from the reaction between singlet oxygen and geminally deuterated tetramethylethylene. An action spectrum for the inhibition of succinoxidase was measured at wavelengths between 400 and 700 nm and found to parallel the recorded visible absorption spectrum of hypericin in isolated mitochondria. The greatest singlet oxygen generation, oxygen consumption, and succinoxidase inhibition occurred with white light or 600 nm irradiation. These data are consistent with a type II singlet-oxygen-mediated mechanism for hypericin induced photosensitized inhibition of mitochondrial succinoxidase. PMID- 1603851 TI - Photosensitization by 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol: damage to erythrocyte membranes, Escherichia coli, and DNA. AB - The natural product 2-chloro-3,11-tridecadiene-5,7,9-triyn-1-ol (1) photosensitized the inactivation of Escherichia coli in the presence of near ultraviolet light (320-400 nm; NUV) under both aerobic and anaerobic conditions. A series of E. coli strains differing in DNA repair capabilities and catalase proficiency exhibited indistinguishable inactivation kinetics following treatment with the chemical plus NUV. The presence of carotenoids did afford some protection to E. coli against inactivation under aerobic conditions, consistent with the involvement of singlet oxygen. The photosensitized hemolysis of human erythrocytes occurred more rapidly in the absence than in the presence of oxygen. Aerobically, the onset of hemolysis was partially inhibited by NaN3 and by 2,6-di t-butyl-4-methylphenol (BHT) but not by superoxide dismutase (SOD). The aerobic lipid peroxidation observed in the membranes of erythrocyte ghosts was completely inhibited by BHT, and partially by NaN3, but not by SOD. These results suggest that either lipid peroxidation of the membrane is not the main cause of photohemolysis or that BHT has insufficient access to intact erythrocyte lipids to protect them. Aerobically, crosslinking of membrane proteins was also observed; it was not affected by SOD, but was partially inhibited by BHT and NaN3. The anaerobic photosensitized hemolysis of erythrocytes was more rapid; a radical mechanism was suggested since BHT inhibited the hemolysis to a greater extent than under aerobic conditions. Neither lipid peroxidation nor protein crosslinking was observed under conditions believed to be anaerobic. A light dependent electron transfer to cytochrome c was obtained under argon but not under oxygen. Although induced mutations were not observed in the experiments with E. coli, 1 was capable of damaging both supercoiled pBR322 and Haemophilus influenzae transforming DNA in a manner that seemed to be equivalent under aerobic and anaerobic conditions. In conclusion, 1 can behave as typical photodynamic molecule under aerobic conditions but, in contrast to most photodynamic molecules, it is also phototoxic under anaerobic conditions. The extent to which the radical reactions detected under anaerobic reactions compete with the photodynamic processes when oxygen is present is not known. PMID- 1603852 TI - A test of the singlet oxygen mechanism of cationic dye photosensitization of mitochondrial damage. AB - Aromatic cationic dyes have a potential as photo-chemotherapeutic agents because they are selectively concentrated into the mitochondria of cancerous cells. The mechanism of cytophototoxicity has been proposed to be primarily due to dye sensitized photogeneration of highly toxic singlet oxygen (1O2) at the mitochondria. We tested this hypothesis by measuring the relative phototoxicity of a collection of aromatic cationic dyes towards respiring rat-liver mitochondria (RLM), upon addition of 514 nm laser light. Effectiveness of dye photosensitization towards destruction of RLM function was assayed by its effect on the RLM membrane potential. Three physical parameters of dye phototoxicity were independently measured and a relative phototoxicity calculated assuming adherence of mechanism to the 1O2 hypothesis. Quantum yields of dye sensitized 1O2 production were estimated, either from time-resolved luminescence measurements of photosensitized 1O2 formed, or by comparing rates of photobleaching of 1O2 trap; the relative partition of dye into mitochondrial lipid was determined gravimetrically; and the optical density of dye was determined in a lipid like Triton X-100 micellar environment. Under the assumption of the 1O2 hypothesis, these parameters were used to predict a relative phototoxicity which was compared with that observed. For 12 of the 14 dyes investigated, the observed and predicted phototoxicities were linearly correlated (r = 0.85) suggesting support of the 1O2 hypothesis. Carbocyanines DiOC2(3) and DiSC2(3) did not correlate and were found to be 10 and 1000 times more potent than predicted, suggesting an additional factor at play in their phototoxicity. PMID- 1603853 TI - Acrylamide quenching of the fluorescence of glyceraldehyde-3-phosphate dehydrogenase: reversible and irreversible effects. AB - The acrylamide quenching of the tryptophan fluorescence of apo and holo glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was studied. In the case of apo GAPDH, the steady state fluorescence quenching cannot be described by the classical Stern-Volmer equation: strong cooperative quenching is observed. In the presence of Pi and/or cofactor NAD+, an inaccessible fraction appears. Cooperative quenching is partially suppressed in the presence of Pi and fully absent in the presence of NAD+. The measurements of the fluorescence lifetimes of the holo-enzyme by phasefluorometry allow the resolution of two lifetimes. The long-lived component is quenched by acrylamide, the short-lived component is not. Quenching induces a red shift of the steady state emission peak. The quenching parameters from the lifetime measurements allow the quantitative description of the steady state fluorescence quenching data. In agreement with the observations of Orstan and Gafni (Photochemistry and Photobiology, (1990) 31, 725-731), we find that acrylamide causes a slow, irreversible loss of activity and a reduction of titratable thiol groups when it acts on the apo-enzyme. This inactivation is strongly reduced in the presence of NAD+. We show that this inactivation is also slowed down by the presence of Pi, and that it is accompanied by a loss of the NAD+ binding site. Blocking the thiol groups with 5,5'-dithio-bis-(2-nitrobenzoic acid) does not lead to a protection against the irreversible inactivation by acrylamide, showing that reactions other than thiol modifications are involved in the irreversible effect. A fraction of the inactivation can be reversed by treatment with mercapto-ethanol. PMID- 1603854 TI - Enhancement of photorepair of ultraviolet-induced pyrimidine dimers by preillumination with fluorescent light in the goldfish cell line. The relationship between survival and yield of pyrimidine dimers. AB - The enhancement of photorepair of UV-induced pyrimidine dimers by preillumination with fluorescent light, previously reported with RBCF-1 cells derived from caudal fin of a goldfish, was studied in terms of clonogenic ability and yields of dimers. In the logarithmic growth phase, the ability of photorepair increased with the time after preillumination, reached a maximum at 8 h, and gradually declined. At 8 h, the dose decrement with the photorepair-treatment for 20 min at 7.5 J/m2 UV increased by preillumination for 1 h from 1.6 to 3.1 J/m2 in terms of restoration of survival and from 1.2 to 4.3 J/m2 in terms of the disappearance of dimers. Incubation of the preilluminated cells in the medium containing cycloheximide (0.5 microgram/mL) after preillumination until UV-irradiation diminished their enhancement of photorepair. In the density-inhibited state, the ability of photorepair was higher than in the log phase, and it was hardly enhanced by preillumination. PMID- 1603855 TI - Odds of being funded by NIH. Understanding percentile ranking and success rates. PMID- 1603856 TI - On the relations between law and quality improvement practice. PMID- 1603857 TI - Managing care and the risk for managing quality. AB - The purpose of this paper is to outline the potential liability of managed care organizations. Specifically, the paper enumerates the various types of liability of health maintenance organizations for the negligent acts of its contracting physicians. The recent cases discussed below demonstrate both the extent to which courts are willing to stretch the liability of HMOs and also the limits that courts place on that liability. PMID- 1603858 TI - Quality assurance implications of federal peer review laws. The Health Care Quality Improvement Act and the National Practitioner Data Bank. AB - Patrick v. Burget, the landmark peer review case holding physicians liable under federal antitrust law for substantial damages caused by bad faith peer review, gave rise to the Health Care Quality Improvement Act. As shown in the recent decision in Austin v. McNamara, the Act's conditional immunities may promote peer review. However, the Act also created the National Practitioner Data Bank, which may have a chilling effect on peer review. The quality assurance implications of each of these federal legal developments is analyzed. PMID- 1603859 TI - Compensation and accountability: the way to improve peer review. PMID- 1603860 TI - A physician's exposure to defamation. AB - The article defines defamation, discusses how to avoid a defamation action, and suggests defenses against a defamation action. Several examples are given that demonstrate common situations where liability exists and how a physician should respond. The article explains that at times we have a duty to speak and differentiates between our legal, moral, and ethical duty. Defamation should not be a concern for those involved in the peer review process, as long as they are truthful or act in a good faith belief that what they are saying is true. The article should enhance peer review by encouraging physicians to participate without fear of a retaliatory law suit. PMID- 1603861 TI - American Medical Association policy positions. PMID- 1603862 TI - American Hospital Association policy positions. PMID- 1603864 TI - [Psychiatric borderline states: theoretical-methodological considerations with reference to Siberian life conditions and the need to development broad public awareness]. AB - With detailed reference to specific conditions of work and every day life in Siberia the authors give insight into methodological, preventive, and rehabilitative efforts to cope with significantly high chronification of patients with borderline symptoms. Special focus is on a complex analysis of ecological, social, psychological, and biological-endogenic factors involved in prevalence, prevention, and rehabilitation. PMID- 1603863 TI - [The dynamics of psychological maladjustment states of chronic stress in inhabitants of areas involved in the Czernobyl nuclear accident]. AB - The authors summarize findings from a 1990 study with 300 inhabitants from areas with various degrees of contamination on psychological, psychiatric, and somatic consequences of the Chernobyl disaster. With critical reference to previous studies and their endogenic interpretation the specific situational and environmental complexity is seen as pathogenetic. The authors discuss the APA DSM III-R 309-89 posttraumatic syndrome and give specifications of this kind of over all, and long term stress. PMID- 1603865 TI - [The importance of Islam religious philosophy for psychiatric practice]. AB - Experience has shown that Muslim patients in psychiatry cause special problems. The article outlines the Islamic religion and demonstrates that Islam embraces all spheres of its follower's life. This causes many kinds of special behaviours and attitudes that have considerable consequences for psychiatric therapy. The consequences in the most important areas of therapy are illustrated, and this should enable the therapist to gain an adequate understanding of the world of his patients. However, if he works often with Muslim patients it will be essential for him to acquire a comprehensive knowledge of the religion on Islam. PMID- 1603866 TI - [Waldheim--a finished topic?]. PMID- 1603867 TI - [Psychiatric family care in the Tapiau/East Prussia Asylum (1907-1940)]. AB - At the end of the so-called "Weimar Republic" in German between the two world wars, and during the time of the Nazi regime, the psychiatric hospital and asylum in Tapiau near Konigsberg/Kaliningrad had the highest incidence of psychiatric patients being looked after on an out-patient basis by host families. Data on this type of psychiatric care by external families were repeatedly published in detail between 1930 and 1937 by Karl Knapp, a psychiatrist who was actively engaged there for many years. After sterilisation of mentally diseased patients had been legally enforced and finances were restricted, family care stagnated, promoting instead a type of family care that was independent of psychiatric hospitals and was carried out on a "district" basis. After 1940, when in the course of enforcement of euthanasia almost all the inmates of psychiatric hospitals and asylums in East Prussia were murdered, the traces of patients entrusted to host family care faded out. PMID- 1603868 TI - Marriage: the whole and its parts. PMID- 1603869 TI - Trouble in paradise: marital crises of midlife. AB - The middle years are said to be the prime of life, a time of anticipated stability and serenity. Middle-aged people describe themselves as "the powerful age group vis-a-vis other age groups"; they say that "they are the norm-bearers and the decision-makers; and they live in a society which, while it may be oriented toward youth, is controlled by the middle-aged" (Neugarten 1968, p. 93). Yet there is trouble in paradise. A large number of couples appear in the therapist's office at midlife, some from long-troubled marriages, but others from marriages that by many standards seemed highly successful. Ironically, they come in large numbers at a time when they seem to be under less strain in many areas of their lives. They may be more financially secure, more established professionally and socially, less controlled by the demands of young children. This reveals something of the internal paradox of marriage, a relationship marked by continual change in the partners and thus continually becoming different from the relationship to which a lifelong commitment was made. Change is most obvious when marked by external shifts in roles due to things such as the birth of a child or a career change. But change is the reality; people do not simply live happily ever after. I will argue that midlife is a key time of change and that the heightened reflection characterizing that period offers unusual opportunities for personal and interpersonal growth at the same time that it confronts people with the changes time has wrought. PMID- 1603870 TI - Quality of marital relationship: a clinical rating scale. AB - Clinical research requires the measurement of complex variables in a manner that is as simple as possible while still being precise. This paper presents a clinical rating scale that was developed as a global measure of the quality of couples' relationships. These couples participated in a study that investigated asthma onset in children at genetic risk for developing this illness. The ratings of marital quality at the prenatal point were significantly related to the number of behavior problems the children were reported to have at 2 years of age. The use of the scale is outlined, together with descriptive data for this group. Reliability data and evidence for predictive and construct validity are presented. PMID- 1603871 TI - The self you seek is the self you find: recent works on the empty, satiated, and/or transformed self. AB - In the past two decades, theorists from a variety of disciplines have written and spoken volumes about what they call "the self." Psychoanalytic theorists, drawing on British object relations, American ego psychology, and Kohut's self psychology have elaborated various sets of schemas of the development of both the healthy and the pathological self and its relations to others; postmodern theorists, drawing on Lacan and Derrida, have elaborated quite different schemas. Feminist theorists, using the lens of gender to focus on the self, have discovered still other possible schemas, even as they acknowledge a debt either to the postmodern or to the object relations tradition. The authors under review here all take as their topic current problems in selfhood and how they affect our relations to others. Most have discovered that contemporary psychoanalytic theory illuminates in new ways our vision of other fields of human activity, such as our relation to the sacred and our relation to literary texts. PMID- 1603872 TI - Mourning the loss of "self as father": a longitudinal study of fatherhood among the Druze. AB - It is within the context of the parent-child relationship--through the processes of attachment, loss, separation and individuation--that we grow and develop interpersonally and intrapsychically (Bowlby 1969, 1980; Mahler et al. 1975; Pollock, 1989). Most developmentalists agree that changes in the parent-child relationship continue to influence both parents and children throughout the life cycle (Cohen et al. 1984; Colarusso and Nemiroff 1982). While there is a vast body of literature devoted to discussing changes that occur in the parent-child relationship during the "formative years," little has been written about what happens to that relationship after the children leave home to start families of their own. Moreover, most researchers investigate the processes of attachment, loss, separation and individuation in terms of the child's development. Little is known about how the child's quest for independence affects the psychological development of his/her parents. Those writers who have addressed the issue of individuation in later life tend to focus on the adult child's continuing struggle to separate and individuate from his/her real or imagined parents (Levinson, 1978). PMID- 1603873 TI - Torture: psychiatric sequelae and phenomenology. AB - Torture has been defined by the United Nations (declaration of December 9, 1975) as "every act by which a public functionary (or another person at his instigation) intentionally inflicts on another person serious pain or suffering, ...physical or mental, with the object of obtaining information or of punishing him...or of intimidating that person or others." In Chile, from the 1973 military coup d'Etat up to the 1988 plebiscite, torture was practiced in a systematic way, as a method of interrogation and as a means of intimidation of detainees and, indirectly, of the population at large. In the beginning, torture was applied in military station units and in police stations, in the facilities of sport fields and prisoners' camps; but above all, in clandestine detention centers and prisons belonging to the secret police (Amnesty International 1977, 1983; CODEPU 1984, 1985, 1986; Lira and Weinstein 1987; Munoz 1986; Rodriguez de Ruiz-Tagle 1978). In spite of the bloodshed of the 1973 coup d'Etat, the phenomenon of torture came as a total surprise for the detainees, who had very often voluntarily surrendered themselves to the new authorities, and who, given the civil traditions of the country, expected treatment in accordance with a society subject to the law. The military government regularly denied having undertaken the practice of torture. According to Lira and Weinstein (20), this denial of such an extreme experience or horror made it even more difficult to overcome the trauma and fostered the development of chronic psychiatric pathology. PMID- 1603874 TI - Psychological and behavioral differences among females classified as bulimic, obligatory exerciser and normal control. AB - The compulsion to maintain a lean body shape while living in a society obsessed with food may encourage the use of dieting, binge eating and purging behaviors in young women. The body of literature on bulimia nervosa (Boskind-Lodahl and Sirlin 1977; Fairburn and Cooper 1984; Katzman and Wolchik 1984; Scott 1988) clearly establishes its relationship to the current American fashion for thinness and the value placed on physical attractiveness for self-esteem. This notion promotes a multitude of weight control strategies ranging from self-starvation (Humphrey 1983; Brownell and Foreyth 1986) to cigarette smoking (Klesges and Klesges 1988), many of which may have a profound influence on maintenance of good health. Similar to weight control, exercise behavior could be viewed as falling on a continuum from reasonable efforts to maintain physical fitness to a preoccupation with exercise that is far out of proportion to the expected benefits of a 30 minute, three to five day a week routine. Characteristics of obligatory exercise have been described by several researchers and include maintaining a rigid schedule of intense exercise; resisting temptation to lapse into nonexercising; feelings of guilt and anxiety when the exercise schedule is violated; compensatory increase in exercise to make up for lapses; pushing oneself even when tired, ill, or injured; mental preoccupation with exercise; and detailed recordkeeping on exercise (Yates et al. 1983; Blumenthal et al. 1984; Nudelman et al. 1988). In a competitive society, obsessive exercise behaviors may be linked to the development of rigid dietary guidelines while one strives toward the "optimal" lean-fat ratio of body composition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1603875 TI - Life structure revitalization: an adult developmental approach to psychodynamic psychotherapy. AB - In this paper we, first, briefly review existing efforts to integrate adult development theory into psychodynamic psychotherapy. Next, we examine the concept of life structure and discuss its evolution across the eras and periods of the adult years. We explore the added concepts of the core self, the vital life structure, and life structure management skills. In so doing, we provide a context for proposing a new definition of the primary task of treatment: to help patients develop life structures that ensure a good fit between internal aspects of the self and the roles, relationships, and activities that comprise their lives. The creation of a life structure that is as fully expressive of the core self as reality permits increases patients' sense of vitality and well-being. PMID- 1603876 TI - Helping chronic psychiatric patients adjust to sociopolitical changes in Poland. AB - According to the stress-diathesis model, persons with serious mental disorders, such as schizophrenia, have cognitive and psychophysiological vulnerabilities that under conditions of stress, lead to psychotic symptoms and diminished interpersonal functioning (Nuechterlein and Dawson 1984; Zubin and Spring 1977). Pharmacological and psychosocial treatments provide buffers to disease vulnerabilities by compensating for neurotransmitter abnormalities, directly reducing the experience of stress, teaching a range of social and instrumental skills that help patients cope with life problems, and dispersing patients' stress through a well-functioning support network (Liberman et al. 1984). To conduct psychosocial treatments well, clinicians must have knowledge regarding the community stressors that impact upon the patient, the range of skills necessary to navigate the hurdles of everyday life (Goldfried and D'Zurilla 1969), and the interpersonal factors that facilitate formation and maintenance of support systems (Tolsdorf 1976). Clinicians can develop individual rehabilitation plans that reflect patients' strengths and weaknesses in each of these areas. PMID- 1603877 TI - Pursuit eye movement dysfunction in obsessive-compulsive disorder. AB - Disturbances in neural circuitry including the basal ganglia and prefrontal cortex have been hypothesized to be a cause of obsessive-compulsive disorder (OCD). Because eye movements are often impaired in neurologic diseases affecting these brain areas, oculomotor functioning was assessed in 17 unmedicated patients with OCD and in 25 normal controls. As compared with control subjects, patients with OCD demonstrated low-gain (slow) pursuit eye movements and an increased frequency of square wave jerk intrusions, but no increase in anticipatory saccades. In addition, several OCD patients showed an unusual pattern of intrusive, brief epochs of high-gain (fast) pursuit lasting on the order of 50 to 130 msec. These epochs of fast pursuit moved the eyes ahead of the target being tracked, and were terminated by corrective reversal saccades. Studies of eye movement abnormalities may provide an informative neurophysiologic approach for studying disturbances in basal ganglia and frontal cortical function that have been observed in functional neuroimaging and neuropsychological studies of OCD. PMID- 1603878 TI - Electroencephalographic sleep studies in depressed outpatients treated with interpersonal psychotherapy: I. Baseline studies in responders and nonresponders. AB - Electroencephalographic (EEG) sleep measures have been examined as predictors of therapeutic response in patients with major depression. Although some studies have reported that EEG sleep measures are predictive of a favorable outcome with medications, two recent studies found no differences in the baseline sleep characteristics of responders and nonresponders to psychotherapy. To clarify this issue, we compared baseline EEG sleep in a group of patients with recurrent depression who responded to interpersonal psychotherapy (n = 19) and a comparable group who did not respond (n = 18). Baseline ratings of depression severity did not differ in the groups, but some differences in baseline sleep were noted. Psychotherapy nonresponders had longer sleep latencies, lower sleep efficiency, and increased automated measures of phasic rapid eye movement (REM) activity. In addition, the two groups had different EEG sleep adaptation patterns for REM latency and phasic REM density measures across the two study nights. These preliminary results suggest that baseline EEG sleep patterns, as well as the pattern of laboratory adaptation, may differ for depressed patients who respond to psychotherapy and those who do not. PMID- 1603879 TI - Electroencephalographic sleep studies in depressed outpatients treated with interpersonal psychotherapy: II. Longitudinal studies at baseline and recovery. AB - Electroencephalographic (EEG) sleep studies may help to identify persistent versus episodic biological characteristics of major depressive disorder. This report examines longitudinal EEG sleep studies in depressed patients treated with psychotherapy alone. Nineteen patients were studied during a symptomatic baseline period and again during early remission after treatment with interpersonal psychotherapy (IPT). EEG sleep findings at baseline were not markedly abnormal, but they were similar to those in other published studies of young adult outpatients. No changes were found in visually scored EEG sleep measures between depression and early remission. Automated measures of delta sleep and rapid eye movement (REM) activity showed small state-related changes, with delta activity increasing from baseline to remission, and automated REM measures decreasing. Strong baseline-remission correlations were noted for most sleep measures, including slow wave sleep, phasic REM activity, and automated delta EEG counts; measures of sleep continuity and tonic REM sleep were not strongly correlated. Consistent adaptation effects across nights were observed for sleep continuity and REM measures during each clinical phase. These findings support the hypothesis that most visually scored EEG sleep measures, as well as the sleep adaptation process, are stable through the acute episode of depression, at least into early symptomatic remission. They also suggest that finer-grained automated analyses of delta and REM activity may provide more sensitive tools for examining state-related changes. PMID- 1603880 TI - Peripheral markers of serotonin and dopamine function in obsessive-compulsive disorder. AB - In an attempt to clarify the possible role of a serotonergic and dopaminergic dysfunction in obsessive-compulsive disorder (OCD), we measured platelet 3H imipramine (3H-IMI) binding, serotonin uptake, and platelet sulfotransferase activity in 17 drug-free OCD patients and an equal number of healthy controls. Serotonin uptake and 3H-IMI binding sites in platelets have been shown to constitute peripheral markers of those present in presynaptic serotonergic neurons. Sulfotransferase, an enzyme involved in the catabolism of phenolic compounds and of cathecholamines such as dopamine, has similar kinetic characteristics in brain and platelets. Our results showed a lower number of 3H IMI binding sites and a higher level of sulfotransferase activity in OCD patients compared with those in controls. These preliminary results suggest involvement of both the serotonin and dopamine systems in OCD. PMID- 1603881 TI - CSF chromogranin A-like immunoreactivity in schizophrenia: relationships with REM latency and slow wave sleep. AB - Chromogranin A (CgA) is a calcium binding protein and a precursor of modulatory peptides in the brain. We measured CgA-like immunoreactivity (CgA-LI) in cerebrospinal fluid (CSF) in 15 male schizophrenic patients (diagnosed by DSM-III R criteria) after 3 nights of polysomnography. Patients had been drug free for at least 33 days. Our earlier report that CSF CgA-LI in schizophrenic patients correlated significantly with negative symptoms and ventricle-brain ratios, which have been related to slow wave sleep, raised the possibility that CgA-LI might relate to slow wave sleep. CSF CgA-LI was significantly correlated with stage 4 sleep and rapid eye movement latency. Whether these positive relationships between CSF CgA-LI and electroencephalographic sleep measures are specific for schizophrenia awaits further study. PMID- 1603882 TI - Test-retest reliability of the prolactin and cortisol responses to D,L fenfluramine challenge in disruptive behavior disorders. AB - We examined the intraindividual stability of plasma prolactin (PRL) and cortisol responses to D,L-fenfluramine challenges (1.0 mg/kg, p.o.), at a 1-week interval, in boys with disruptive behavior disorders. Two acute administrations of fenfluramine produced consistent and predictable effects on net prolactin responses (peak delta PRL, area under the curve delta PRL), but variable and unpredictable effects on net cortisol responses. The time course and magnitude of fenfluramine blood levels, not nor-fenfluramine, paralleled net PRL responses to fenfluramine. These data indicate that the PRL response to fenfluramine shows continuity within individuals over the course of 1 week, providing a reliable index to reflect the overall function of the serotonin system in the limbic hypothalamus. PMID- 1603883 TI - The thyroid and melancholia. AB - Several studies that have examined heterogeneous groups of patients suggest that altered thyroid function may distinguish melancholic from nonmelancholic depression. We therefore measured basal thyroid hormone levels in 90 unipolar depressed patients who were divided into melancholic and nonmelancholic subgroups according to three definitions. Levels of thyroxine, triiodothyronine, and thyrotropin, obtained using an ultrasensitive assay, did not distinguish the subtypes of depression. However, severity of depression contributed significantly to the difference between these subtypes according to DSM-III and Research Diagnostic Criteria. PMID- 1603884 TI - Fenfluramine stimulation of prolactin in obsessive-compulsive disorder. AB - The success of serotonergic reuptake inhibitors in the treatment of obsessive compulsive disorder (OCD) has suggested that serotonergic neurotransmission may play a role in the pathogenisis of this disorder. Prolactin responses to a 60-mg oral dose of fenfluramine in 26 medication-free patients with a DSM-III-R diagnosis of OCD were compared with those of 20 controls subjects. Fenfluramine produced a significant elevation of prolactin levels in both OCD patients and controls. Prolactin responses were significantly blunted in OCD patients compared with responses in control subjects. Female subjects in both groups showed greater prolactin responses to fenfluramine than did their male counterparts. There was a significant interaction between sex and the presence of OCD such that female patients had lower prolactin responses than their controls, while the difference between male patients and controls was not significant. Prolactin responses were not correlated with age, weight, drug level, depression, anxiety, or degree of OCD symptoms. The results are consistent with a relative reduction in serotonergic efficacy in the setting of OCD. PMID- 1603885 TI - Prevalence of personality disorders in patients with major depression and dysthymia. AB - The authors administered the Structured Clinical Interview for DSM-III-R Axis I (SCID-P) and Axis II (SCID-II) Disorders to 197 patients with major depression, 63 patients with dysthymia, and 32 patients with both major depression and dysthymia ("double depression"). Fifty percent of major depressive patients, 52% of dysthymic patients, and 69% of patients with double depression were diagnosed as having at least one personality disorder. Patients with a personality disorder had higher scores on the Beck Anxiety and Depression Inventories. The most commonly diagnosed personality disorders were from the anxious/fearful cluster, most notably avoidant and dependent personality disorders. PMID- 1603886 TI - Error in chess: the apperception-restructuring view. AB - Five protocol-analysis experiments with tactical, endgame, and strategic positions were conducted to study cognitive errors in chess players' thinking. It will be argued that chess players' errors can be only partially explained in terms of unspecified working-memory overload, because the working-memory loads caused by the solution paths are usually small. It is therefore necessary to consider apperceptive mechanisms also, as these control information intake. Subjects fail either because they are not able to see the right prototypical problem space at all, or because they fail to close them as a result of missing some crucial task-relevant cue. This makes chess players lose their "belief in the idea" and restructure, after which the apperceptive information-selection mechanisms make the finding of the solution still more unlikely. PMID- 1603887 TI - Learned helplessness in chess players: the importance of task similarity and the role of skill. AB - The effects of noncontingency between subjects' responses and outcomes were examined with respect to treatment-and-posttest similarity and skill in the task. The experimental design consisted of three groups. The first group had to solve chess problems with objective solutions and received veridical feedback; each member of the second group faced problems with no objective solutions, and received the same feedback as the member of the first group he was yoked with, but without any control on it; the control group received a waiting task. It was found at the end of the experiment that the group with unsolvable problems was more depressed than the two other groups. The mid-strength players were the most sensitive to the manipulation, and the weakest players showed little effect of learned helplessness. It was also found that the effects were proportional to the degree of similarity between the treatment and the posttest. The results limit the domain of applicability of the learned-helplessness model. PMID- 1603888 TI - Children and chess expertise: the role of calibration. AB - Three studies of calibration are reported. Calibration refers to the accuracy with which one can predict one's own performance. In the first study child chess players, non-chess playing parents, and statistics students were asked to predict chances of winning chess games against hypothetical opponents. These subjective probabilities were compared to the actual probabilities, based on the Elo rating system. Better players' predictions were better calibrated. Confidence and ratings are negatively correlated, indicating that with lower ratings, players re overconfident. Skilled child players' predictions were better calibrated than any of the adults'. In the second study subjects were asked to estimate chances of winning in conjunctive situations, e.g., winning all the rounds in a tournament. Again, better child players were more accurate in their predictions and more accurate than adults. In the third study, child players were asked to predict their chances of winning in a non-chess domain after hearing a hypothetical win/loss history. Higher-rated players' predictions were again better calibrated, even though the domain was outside their expertise. The motivational and cognitive implications of calibration are discussed. PMID- 1603891 TI - Effects of oral BMY 21502 on Morris water task performance in 16-18 month old F 344 rats. AB - In the present study we have examined the effects of oral administration of BMY 21502, a potential cognition enhancing drug, on the impaired Morris water task performance of 16-18 month old F-344 rats. BMY 21502 did not affect swim speeds or performance on the first trial of each day, but it did increase the rate of acquisition and initial retention, resulting in decreased swim distances on the second trial of each day. This increased rate of acquisition was dose-dependent, increasing to a peak at 5.0 mg/kg; the effect was decreased at 10 mg/kg, but still above control values. These results suggest that BMY 21502 is orally active over a broad range of doses, and lend further support for its potential as a therapeutic agent for the treatment of dementia. PMID- 1603890 TI - Rebound insomnia and hypnotic self administration. AB - Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine whether or not rebound insomnia would increase the likelihood of self administering a benzodiazepine (triazolam 0.25 mg) hypnotic. The groups compared were patients with insomnia and disturbed sleep, insomnia and normal sleep, and healthy normals. Rebound insomnia, by both subjective and polysomnographic assessment, was induced. The experience of rebound insomnia did not increase the likelihood of self administering a benzodiazepine hypnotic in any of the groups. There were clear group differences in pill self administration with normals rarely and insomnia patients frequently, but not differentially (placebo versus active drug) self administering pills. PMID- 1603889 TI - Behavioral screening for cognition enhancers: from indiscriminate to valid testing: Part II. PMID- 1603892 TI - Early dyskinesia--vulnerability. AB - Relative vulnerability to dyskinesia in terms of exposure to antipsychotic drugs prior to onset of dyskinesia was studied in a sample of 100 psychiatric patients with dyskinesia onset generally within a year or less of the point of study entry. Unipolar and bipolar patients were more vulnerable to dyskinesia than other diagnostic groups. In the total sample, lithium exposure did not appear to delay development of dyskinesia. Longer exposure to antiparkinson drugs was associated with delayed onset of dyskinesia. Past exposure to electroconvulsive therapy was related to decreased vulnerability to dyskinesia. PMID- 1603893 TI - Acute and chronic ethanol tolerance: operant behaviour in naive and ethanol tolerant rats. AB - The relationship between tolerance to ethanol and acute tolerance to ethanol was examined. One group of rats was given 1.8 g/kg ethanol, and another group was administered 18 ml/kg saline for 26 days after sessions. Animals responded under a fixed ratio ten (FR-10) schedule of food reinforcement. Thereafter, various doses of ethanol (1.3-2.5 g/kg) were examined to assess the influence of the ethanol treatment on the expression of acute tolerance. Acute tolerance was assessed by comparing the performance at equal concentrations of ethanol on the ascending and the descending limbs of the ethanol concentration curve. This was achieved by varying the time between behavioural tests since ethanol administration. Ethanol concentrations were estimated using a rebreathed air procedure. Equal concentrations of ethanol were achieved with doses of i) 1.3 g/kg (10 min post-injection, PI), and 1.8 g/kg (60 min PI), as well as with doses of ii) 2.0 g/kg (10 min PI), and 2.5 g/kg (60 min PI). Acute tolerance was demonstrated for the initially ethanol naive animals. For the animals given ethanol chronically, only doses of ethanol higher than the chronically administered dose produced evidence for acute tolerance. When the chronically dosed animals had been off ethanol for 67 days, there was evidence for acute tolerance. The present data add to the generality of the acute ethanol tolerance phenomenon, and emphasize both the appearance as well as the loss of tolerance for this effect. PMID- 1603894 TI - Conditioned morphine withdrawal in the hamster. AB - Conditioned withdrawal among golden Syrian hamsters was studied in two experiments. In experiment 1, morphine-pelleted (75 mg) hamsters were observed for signs of withdrawal (wet-dog shakes, etc.) before and after a naloxone (1 mg/kg) injection that was administered in a distinctive environment. Withdrawal signs that occurred in the distinctive environment before the naloxone injection were defined as anticipatory conditioned withdrawal responses. Two, 9, and 30 days following pellet removal, retention of conditioned withdrawal responding was assessed in the distinctive environment before and after a saline injection. Results indicated that: a) withdrawal intensity was a direct function of the number of implanted pellets; b) conditioned withdrawal occurred among animals withdrawn in the distinctive environment, but not among those withdrawn in the home cage; c) conditioned withdrawal was a nonmonotonic function of precipitated withdrawal intensity; d) conditioned withdrawal was evident up to 30 days after pellet removal. In experiment 2, conditioned withdrawal was extinguished by repeated exposure to the distinctive environment in the absence of precipitated withdrawal. It was concluded that environmental stimuli associated with the absence of morphine (i.e., precipitated withdrawal) elicit conditioned withdrawal. The results are compared to similar findings in rats and humans. PMID- 1603895 TI - Conditioned responses to cocaine-related stimuli in cocaine abuse patients. AB - Subjects with a history of free-basing and smoking cocaine but no history of opiate injections were exposed to three sets of stimuli. They received cocaine related stimuli in one session, opiate-related stimuli in a second session, and non-drug stimuli on a third occasion. Compared to the opiate and non-drug cues, the cocaine-related events caused reliable decreases in skin temperature and skin resistance, and reliable increases in heart rate, self-reported cocaine craving, and self-reported cocaine withdrawal. Furthermore, control subjects lacking a history of cocaine or opiate use failed to show such differential responding. These results suggest that cocaine-related stimuli evoke Pavlovian conditioned responses in cocaine abuse patients. Such findings encourage continuing efforts to develop drug treatment strategies based on conditioning principles. PMID- 1603896 TI - Effects of systemic and intracerebroventricular administration of mecamylamine, a nicotinic cholinergic antagonist, on spatial memory in rats. AB - The effects of both systemic and intracerebroventricular administration of mecamylamine, a nicotinic antagonist, were tested on the Morris water maze performance of rats. In experiment 1, mecamylamine (0, 3, and 10 mg/kg, IP) was administered before daily training sessions on the Morris water maze, a task in which rats use environmental cues to learn the location of an invisible escape platform in a large pool of water. The escape latencies of rats given the higher dose of mecamylamine were significantly longer than the latencies of rats given either saline or the peripherally-acting nicotinic antagonist hexamethonium (10 mg/kg). Analysis of search patterns during a free swim trial conducted in the absence of an escape platform confirmed the disruptive effects of the higher dose of mecamylamine. Similar drug effects were not observed when these rats were trained to a visible platform, and mecamylamine did not affect the retrieval of spatial information in well-trained rats. In experiment 2, similar effects were observed with ICV administration of mecamylamine (0, 10, 30, and 100 micrograms). The two higher doses increased escape latencies during the last day of place training and all three doses significantly impaired performance on a free swim. No significant effects were noted on subsequent training to a visible platform, and only the highest dose marginally impaired the retrieval of spatial information in well-trained animals. Thus, mecamylamine appears to impair the acquisition of spatial information in the Morris water maze but does not affect retrieval of previously acquired spatial information at comparable doses. PMID- 1603897 TI - Effects of alprazolam and imipramine on parasympathetic cardiac control in patients with generalized anxiety disorder. AB - A noninvasive measure was used to assess the effects of alprazolam, imipramine and placebo on parasympathetic (vagal) cardiac control following 6-weeks of medication in patients with generalized anxiety disorder. Flexible dosage at therapeutic levels resulted in increased heart rate and blood pressure and in decreased cardiac vagal control in patients receiving imipramine but not alprazolam or placebo. About 50% of the variance in heart rate changes and changes in mean arterial blood pressure following treatment with imipramine could be accounted for by changes in cardiac vagal control. Decreased cardiac vagal control can now be added to the list of cardiovascular changes seen following several weeks of treatment with imipramine. PMID- 1603898 TI - Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms. AB - The behavioral effects of GABAergic manipulation of the basal forebrain were investigated using two behavioral tasks, which previous studies have shown to yield dissociable effects following quisqualate-induced lesions of the basal forebrain: a five-choice serial reaction time task, involving approaching the location of a brief visual stimulus that is associated with reward; and a conditional visual discrimination task, requiring retrieval of information about a discriminative stimulus that stays constant over time. Following acquisition of the tasks, chronic guide cannulae were stereotaxically implanted into the basal forebrain. Those animals trained on the conditional visual discrimination task showed a dose-dependent reduction in choice accuracy and a lengthening of latency to respond correctly to the visual stimulus following administration of the GABA A agonist, muscimol (1, 2, 3 ng/microliters/hem). While certain of these deficits, for example response latency, could be restored to control levels by co administration of the GABA-A antagonist, bicuculline, none of the behavioural impairments could be significantly attenuated by systemic by systemic co administration of the cholinesterase inhibitor, physostigmine (0.05, 0.1, 0.2 mg/kg, IP). Similarly, a dose dependent effect of muscimol (1, 1.5, 2 ng/microliters/hem) on choice accuracy and correct response latency was observed on performance of the five-choice attentional task. However, in contrast to the conditional task, significant attenuation of the impairment in choice accuracy was obtained following administration of physostigmine (0.05 and 0.1 mg/kg). Attenuation of muscimol-induced deficits by administration of bicuculline was also observed. It is therefore evident that although manipulation of GABAergic activity in the region of the basal forebrain produces profound deficits in different tasks of cognitive function, only some of these may be due to modulation of the magnocellular cholinergic projection to the neocortex. PMID- 1603899 TI - Alcohol and "bursts" of aggressive behavior: ethological analysis of individual differences in rats. AB - A quantitative ethological analysis of rodent aggression was performed in order to characterize the aggression-heightening effects of alcohol in certain individuals. In dyadic confrontations, a resident rat pursues, threatens and attacks an intruder, who reacts with defensive, flight and submissive behaviors. The behavioral data from five series of experiments conducted from 1984 through 1989 were subjected to a lag sequential analysis that identified highly predictable sequences of aggressive behavior, and to interval analysis that delineated a burst pattern of aggressive behavior. These analyses revealed a distinct behavioral sequence of pursuit----sideways threat----attack bite--- aggressive posture that occurs in bursts with an inter-event interval of less than 6.6 s. In the total population, alcohol heightened attack behavior at low acute doses (0.1, 0.3, 1.0 g/kg) in 47% of the animals (n = 44), suppressed reliably attack behavior in another 25% (0.1-3.0 g/kg; n = 23) and had unreliable effects in the remaining 28% (n = 24). The peak enhancement of aggressive behavior was seen over more than a log cycle of alcohol doses (0.1, 0.3 or 1.0 g/kg) in different individuals. In an additional group of rats (n = 20), individuals were identified according to whether or not acute low alcohol doses enhanced or suppressed the frequency of attack bites. In the subgroup of five rats who doubled their attack frequency upon acute alcohol challenge, this aggression-heightening effect was confirmed on repeated occasions. The aggression heightening effects of alcohol were seen during the high-rate interactions in the initial phase of the confrontation and particularly during the lower level of fighting later on. Regardless of alcohol dose and subgroup, the highly predictable sequence of pursuit----sideways threat----attack bite----aggressive posture remained intact as long as the individual was able to fight. The present analysis identifies those individuals in whom low alcohol doses increase the frequency of attack behavior, the number of aggressive elements in bursts and particularly the "time in burst". Alcohol produces these changes without altering the latency to initiate aggressive behavior, the rate of aggressive behavior within a burst or the number of bursts in an encounter. Alcohol may lengthen aggressive bursts by preventing termination of longer aggressive sequences rather than by altering the initiation of this behavior. PMID- 1603900 TI - Differences in response to the aversive properties and activity effects of low dose ethanol in LAS and HAS selectively bred rats. AB - Rats selectively bred for high alcohol sleep times (HAS) and those that are less affected (LAS) by hypnotic doses (3.0-3.6 g/kg) of ethanol were tested for differential responses to the aversive effects of 1.0 g/kg ethanol in a conditioned place preference task. Likewise, the effects of 0.3-1.0 g/kg ethanol on spontaneous locomotor activity over a 30-min period, as well as the loss of righting reflex with a higher ethanol dose (3.0 g/kg), were determined in these animals. The LAS rats reacted more aversively to 1.0 g/kg during conditioned place aversion testing than the HAS animals and also had a shorter mean sleeping time following 3.0 g/kg ethanol. Furthermore, dose-related depression of spontaneous motor activity was seen in the HAS animals and not in the LAS animals over a 30-min period using doses of 0.3, 0.6, or 1.0 g/kg (10% w/v) ethanol. Taken together, the results indicate that the intoxicating sequelae of high ethanol doses, such as ataxia and sedation, may not be correlated with the aversive effects of low ethanol doses. PMID- 1603901 TI - Effects of trazodone on EEG sleep and clinical state in major depression. AB - The effects of the antidepressant trazodone on clinical state and on EEG sleep in eight outpatients with a major depressive disorder were investigated in a single blind study. A medication period of 5 weeks was preceded and followed by one week placebo treatment. Five subjects showed a positive treatment response. Trazodone did not influence sleep continuity and slow wave sleep, but did suppress REM sleep significantly. A significant increase of REM sleep latency was also found. These results are in contrast with earlier reports on trazodone's effects on EEG sleep but are in accordance with the general finding that antidepressants influence REM sleep characteristics without necessarily affecting sleep continuity. PMID- 1603902 TI - Clonidine and yohimbine modulate the effects of naloxone on novelty-induced hypoalgesia. AB - Previous research has shown that repeated daily pretreatment with the opiate receptor blocker naloxone retards the development of habituation to novelty induced hypoalgesia. The present experiments were conducted in order to determine whether noradrenergic substrates mediates this effect. Animals in the NAL condition were administered 10 mg/kg naloxone prior to assessment of pain sensitivity on a 48.5 degrees C hot plate. Control animals (SAL condition) were administered saline prior to pain assessment, and naloxone 2-4 h later. Paw lick latencies declined over repeated tests in SAL animals, suggesting the habituation of novelty hypoalgesia. Naloxone pretreatment attenuated this decline. The longer paw lick latencies observed in NAL condition animals were reduced by administration of 2 microgram/kg clonidine, a specific noradrenergic alpha-2 receptor agonist, and enhanced in a dose dependent (0.5-4.0 mg/kg) fashion by the alpha-2 antagonist yohimbine. Clonidine and yohimbine either failed to alter pain reactivity in control animals, or produced less marked effects than those observed in naloxone-exposed animals. These results suggest that noradrenergic substrates mediate naloxone's effects on novelty hypoalgesia. PMID- 1603904 TI - Reduction of sexual activities in females taking antiepileptic drugs. AB - Studies of male or sexually unspecified populations have revealed loss of libido and decreased sexual function in patients with epilepsy taking antiepileptic drugs. The relative contributions of antiepileptic drugs, seizures, brain injury, and social factors have not been clearly delineated. We studied sexual activity in a group of females taking antiepileptic drugs, and defined a subgroup with pronounced hyposexuality. PMID- 1603903 TI - Morphine, D-Pen2, D-Pen5 enkephalin and U50,488H differentially affect the locomotor activity and behaviours induced by quinpirole in guinea-pigs. AB - The effects of morphine D-Pen2, D-Pen5 enkephalin (DPDPE) and U50,488H on the behavioural syndrome elicited by the dopamine (DA) D-2 agonist quinpirole, were investigated. Morphine (1, 5 and 15 mg/kg SC) and morphine administered intracerebroventricularly (ICV) (2 x 5 microliters, 10(-3) M; total dose = 10 nmol) produced piloerection and sedation. DPDPE-ICV (2 x 5 microliters and 2 x 10 microliters, 10(-3) M; total doses = 10 and 20 nmol) produced piloerection and sedation similar to morphine. U50,488H (1 mg/kg SC) induced locomotor activity and some stereotyped behaviour, whereas U50,488H (5 and 10 mg/kg SC) induced muscle rigidity and dystonic-like movements. The locomotor and behavioural response elicited by quinpirole (3 mg/kg IP) was attenuated in guinea-pigs pretreated with morphine (1, 5 and 15 mg/kg SC), morphine-ICV (2 x 5 microliters, 10(-3) M), and DPDPE-ICV (2 x 5 microliters and 2 x 10 microliters, 10(-3) M). These effects were reversed by naloxone (15 mg/kg SC). U50,488H (1 mg/kg SC) increased the quinpirole-induced locomotor activity, whereas U50,488H (5 and 10 mg/kg SC) decreased the locomotor activity and stereotyped behaviours produced by quinpirole. These results indicate that the gross behavioural effects of mu, delta and kappa opioids differ in guinea-pigs compared to other rodent species, and suggest differential involvement of these opioid receptor subtypes with DA D 2 receptor-mediated activity. PMID- 1603905 TI - Age at onset, precipitating events, sex distribution, and co-occurrence of anxiety disorders. AB - 178 outpatients were administered to a structured interview evaluating diagnostic, illness history, and sociodemographic data of DSM-III-R anxiety disorders. Patients with panic disorder with agoraphobia were a more severely ill subgroup than patients with panic disorder without agoraphobia. Simple and social phobia had the earliest age at onset, panic disorder the latest age at onset. Conjugal stress was the most frequent event preceding the onset of the anxiety disorders. Female patients showed more severe impairment suffering more frequently from concomitant phobic avoidance, generalized anxiety, and depression compared to male patients. PMID- 1603906 TI - Psychotic symptoms and age of onset in affective disorders. AB - Prevalence of hallucinations and delusions was studied in 1,763 patients with unipolar major depression, bipolar affective disorder, and schizoaffective disorder. The authors found that the presence of psychotic features was negatively associated with age of onset for the group as a whole, and bipolar affective disorder (manic or mixed type) specifically. The clinical implications of the findings are discussed. PMID- 1603907 TI - Alterations of drive in differential diagnosis of mild depressive disorders- evidence for the spectrum concept of endogenomorphic affective psychosis. AB - Specific alterations of drive have been cited in the literature to separate mild depressive disorders belonging to the bipolar or endogenomorphic spectrum from depressive disorders of other origin. To test this hypothesis 44 patients with mild depressive disorder were studied longitudinally. Presence of inhibition of drive or thought predicted outcome in mania or melancholia. The data are interpreted as evidence for the spectrum concept of affective psychosis. PMID- 1603908 TI - Use of the speed accuracy trade-off to characterize information processing in schizophrenics and normals. AB - Subjects performed a signal discrimination task under four conditions: normal pace, accuracy, speed, and SATO (equal effort to speed and accuracy). Characteristically, schizophrenics demonstrated decreased accuracy, poorer compliance, increased total response time, and increased simple reaction time. Surprisingly, central processing time (decision time) was equivalent. Analysis of processing resource allocation identified significant group differences only under the SATO condition. Here, controls balanced attentional resources but patients worked almost exclusively for speed. Under conjoint performance conditions, patients apparently minimize categorical processing time at the expense of accuracy. These data are interesting as they identify specific circumstances under which schizophrenics manifest an attentional deficit. PMID- 1603909 TI - The 'diagnostic history' of schizophrenia. A retrospective study of 84 Swedish inpatients. AB - Since few studies have focused on the diagnostic process foregoing a case record diagnosis of schizophrenia, the present study was undertaken with the aims to examine the time interval between the onset of the illness, the first admission as inpatient, and the timepoint of a case record diagnosis of schizophrenia. Further, the study aimed at analyzing the influence of demographic and clinical variables on an 'early' or 'late' diagnosis of schizophrenia. The records of 84 inpatients treated during the calendar year 1986, were retrospectively analyzed. Only 21.4% of the patients had received a case record diagnosis of schizophrenia at their first admission into hospital, and additionally 16.7% after two admissions. Those patients with 'early' diagnosis differ significantly from patients with 'late' diagnosis, being more frequently men, having longer admission latency, higher frequency of Schneiderian first-rank and negative symptoms, a longer stay at hospital at their first admission, and lower levels of working capacity at the onset of the illness. The data suggest a propensity to include course and social functioning aspects of poor outcome in the diagnostic process. Confining the diagnosis of schizophrenia to the severe cases indicates a conservative, perhaps tautological, approach to this diagnosis. PMID- 1603911 TI - Leading for health. PMID- 1603910 TI - Psychotic symptom patterns and the diagnosis of schizophrenia. AB - In comparing 101 psychotic patients subtyped by DSM-III criteria into paranoia, schizophrenia, schizoaffective, and affective disorders, we failed to distinguish them on the basis of delusional and hallucinatory experiences. These 'productive', 'positive' or 'irritative' symptoms--which the literature tends to link with temporolimbic dysfunction--did not appear specifically linked to schizophrenia. By contrast, 'negative' or 'deficit' symptoms--which the literature tends to relate to frontal lobe dysfunction--appeared more specific- especially for the disorganized subtype of schizophrenia. Although these data tend to support Bleulerian over Schneiderian conceptualization of schizophrenia, the heterogeneity of neuropsychological deficits implied in the negative symptom complexes limits the nosologic utility of the rubric of schizophrenia so defined. PMID- 1603912 TI - Time trends of haemoglobin levels and anaemia prevalence in infancy in a total community. AB - In order to determine the trends in haemoglobin (Hb) levels and the prevalence of anaemia in infancy in an entire community, 3,147 infants aged 9-11 months attending the Mother and Child Health Clinics of the teaching and research Health Center in Kiryat Hayovel, Jerusalem, were examined. From 1971 to 1979 infants diagnosed as anaemic were given treatment. From 1980 to 1988 supplement was given to all infants from the age of 3 to 12 months. There was a mean increase of 0.6 g/dlHb between the two periods, with a larger increase in the Hb levels in 1980 88 as compared to 1971-79 (P = .0001). The prevalence of anaemia less than 11 g/dlHb decreased from 36% in 1971 to 27% in 1979 and to 19% in 1988. The prevalence of anaemia less than 10 g/dlHb decreased from 13.7% in 1971 to 8.7% in 1979 and to 3.6% in 1988. The time trend is probably due to changes in the socio demographic characteristics of the population, an overall change in infant feeding practices in relation to iron source and the supplementation programme. PMID- 1603913 TI - Coping with an upper limb fracture? A study of the elderly. AB - Upper limb fractures in the elderly, usually managed by immobilisation of the arm, limit activities to an unknown extent. Fifty-one patients in Middlesbrough, aged over 60 years and who had upper limb fractures, were interviewed in the fracture clinic. Most patients had difficulty in performing various activities of daily living (ADL) following their injury. Difficulties with ADL were significantly associated with shoulder immobilisation (P = 0.03) and age (P = 0.01) but not with life satisfaction (P = 0.18) or existing poor health (P = 0.39). Relatives and friends provided most of the necessary help, the contribution of the health and social services being relatively small. Patients received more help with activities like shopping, laundry and housework than personal activities such as bathing, using the toilet and dressing. The injury increased demands on the GPs, meals on wheels, home help, nursing and warden services. Unmet demand was mostly for chiropodists, bath attendants and physiotherapists. Most patients (95%) were satisfied with the help they received from their relatives and friends. Despite difficulty with the activities of daily living most patients coped well with support following their fracture. Demographic changes and the increasing incidence of fractures mean that the burden on both carers and health and social services will increase. PMID- 1603914 TI - Confidence intervals and interval cancers ... needles and haystacks? AB - The measurement of interval cancer rates will be critical to the successful evaluation of the breast cancer screening programme. The number of interval cancers expected in a district will depend on the population size, the test sensitivity and the background incidence of breast cancer. The present study was undertaken to measure the incidence of breast cancer in Northern Ireland, and to assess the practical problems that might be encountered in ascertaining interval cancers. Given a local yearly incidence of 182/100,000, only 14 interval cancers per year might be expected in Northern Ireland (population 1.5 million). The completeness of the local cancer register would not ensure reliable detection of this relatively small number of tumours. To give larger samples sizes and thus narrow the confidence intervals of measured rates, the results from several smaller regions could be aggregated. Different regions may have different mechanisms of ascertainment and this may make the interpretation of these rates more difficult. PMID- 1603915 TI - Spanish toxic oil syndrome: ten years after the disaster. AB - Toxic oil syndrome (TOS), a previously undescribed disease that occurred in Spain in epidemic form in 1981, has been associated with ingestion of a reprocessed denatured rapeseed oil illegally marketed. However, the association between the syndrome and the adulterated rapeseed oil rests exclusively on epidemiological data because of the absence of toxicologic confirmation and the inability to reproduce the disease in animals. An analysis of the epidemiological evidence available on TOS is carried out in this paper, in an attempt to elucidate the aetiological role of the purported toxic oil. The adulterated oil was found to be highly statistically associated with the syndrome, such an association being extremely unlikely to be due to the effects of bias and/or confounders. The association is very strong, as the estimated relative risk shows (odds ratio = 30), and a dose-response relationship was found. Likewise, the specificity of the association is very high. The temporal sequence of events, although not entirely clear, also helps to support the hypothesis of causality. No other criterion was met, but none of these unmet criteria stands against this hypothesis. From these findings, the adulterated rapeseed oil can be considered a necessary cause for the syndrome to have occurred. Further toxicologic investigations are required to elucidate the precise toxic agent. PMID- 1603916 TI - The Finnish Family Competence Study: fathers of young families as users of health care services. AB - STUDY OBJECT: Fathers of young families as users of health care services. DESIGN: Randomized cluster sampling and confidential questionnaires. SETTING: Maternity health care clinics (MHCCs). PARTICIPANTS: The first phase of the Finnish Family Competence Study included a total of 1,414 fathers of young families expecting their first baby. Of these, 1,279 responded to the questionnaire, the drop-out rate being 9.5%. The third phase included a total of 1,279 fathers of young families after their first baby's birth. Of these, 1,161 responded to the questionnaire, the drop-out rate now being 9.2%. VARIABLES: Basic educational level, age and occupation were used as demographic variables. Socio-economic factors were also studied. The use of health services was examined with questions related to the quality and the frequency of use of these services. The study also dealt with the use of medicines and health food products. RESULTS: The frequency of use of health services was related to the respondent's occupation: industrial and primary production employees were the most frequent users and professionals and services sector employees the least frequent users. So-called soft medicines (vitamins, micronutrients, etc.) were most frequently used by the respondents with the highest level of education. In the use of other medicines no differences occurred between education groups. PMID- 1603917 TI - Can family violence be prevented? A psychosocial study of male batterers and battered wives. AB - This study is based on interviews with 18 male wife-beaters and 49 battered wives. It was designed to establish the importance of such social background factors as violence and alcoholism in the family of origin for the eruption of similar problems in the next generation. The study concludes that battered wives and male batterers have a similar social background and that a vast majority of them have experienced violence in childhood and that half of them came from homes where the father was a heavy consumer of alcohol. As adults, the boys repeat the behaviour of their fathers and the girls repeat the behaviour of their mothers. To prevent wife abuse we must extend the scope from the battered wife to the whole family. Only by focusing on the conditions under which the children of the battered wife grow up can family violence be prevented in the future. PMID- 1603918 TI - A review of data on measles cases from sentinel surveillance sites in north western Nigeria. AB - This review was carried out to evaluate the impact of the revised Expanded Programme on Immunisation (EPI) against measles in the six north-western states of Nigeria through the sentinel surveillance system. The revised EPI was launched in all states by 1985, with a strategy of phased acceleration to reach all local government areas by 1987, and to achieve 80% vaccine coverage of children under two years, with 50% reduction in EPI disease morbidity by 1990. Results of the review showed a dramatic decrease in measles cases in each state: 70% overall from 1985 to 1988. Of 918 cases with known measles vaccination status, 90.6% were unvaccinated and 9.4% had documented immunisation. One concern is that 19% of cases occur in unimmunised infants under nine months. Although a suitable vaccine for children under nine months is available, it is not yet in use in Nigeria and these cases are therefore not preventable. At present, our best strategy is to increase coverage through a vigorous EPI campaign, concentrating on underserviced and hard-to-reach areas, and to strengthen surveillance so that measles outbreaks are identified early and action taken. PMID- 1603920 TI - Public health versus public policy? An appraisal of British urban transport policy. PMID- 1603919 TI - The human environment, occupation, and possible water-borne transmission of the human hookworm, Necator americanus, in endemic coastal communities of the Niger Delta, Nigeria. AB - A 15-month longitudinal study was carried out in four riverine communities of the Niger Delta to ascertain the impact of the environment and occupation on the transmission and infection pattern of the human hookworm Necator americanus. A total of 925 (50.10%) individuals were found to be infected. Male and female infection rates were 54.26% and 47.96% respectively. The difference was statistically significant (P less than 0.05). The prevalence of infection, the egg counts, and the seasonal incidence were related to the occupations and mode of transmission. The highest occupation prevalence of 60.92% occurred among the fishermen through water-borne transmission, while prevalence rates of 52.96% and 52.4% were recorded respectively through soil transmission. The difference between fishermen's prevalence and farmers' prevalence was statistically significant (P less than 0.01). Farmers' egg counts varied from 1,500 eggs per gram (epg) in the dry season to 7,500 epg in the rainy season. Fishermen's egg counts ranged from 3,000 epg in the rainy season to 8,000 epg in the dry season. The difference was not significant (P greater than 0.05). Among farmers the highest monthly incidence of 25% occurred in June, while the highest incidence of 35% occurred in fishermen in April. Incidence of infection among fishermen remained significantly higher (P less than 0.05) than in other occupation groups during the dry season months. Water-borne transmission of hookworm probably increases the incidence and egg counts among fishermen during the dry season. PMID- 1603921 TI - Are the elderly being short-changed by the NHS? PMID- 1603922 TI - Medical ethics and the public health. AB - The development of preventive medicine is reviewed from an historical perspective. In its third and current stage of development preventive medicine has become involved in the life cycle of individual diseases and this presents a number of ethical difficulties for doctors and not least those concerned with the public health. Some proposed responses are considered and rejected. It is concluded that participants should be given more detailed information about screening tests and that doctors are under an ethical obligation to consider with the utmost care any contra-indications to a particular vaccination or a screening procedure in an individual patient. Serious reservations are expressed about the ethics and scientific justification of some government preventive medicine programmes currently in operation or projected. PMID- 1603923 TI - The problems of monitoring tuberculosis in an inner-city health district: integrated information is required. AB - This paper discusses the difficulties in monitoring tuberculosis in an inner-city district health authority. Tuberculosis incidence was reviewed between 1981 and 1989 using several data sources: statutory notifications, hospital activity analysis, death certificates and chest clinic records. The overall notification rate declined but remained higher than national rates; the age-sex distribution was similar to national studies. However, interpretation was limited by the problems of small numbers, the difficulty in obtaining reliable numerator and denominator estimates of ethnic groups, the limited data available about sub groups of concern such as the homeless, and finally by the incompleteness of the data. Improved methods of data linkage are required to facilitate more complete ascertainment and validation of the diagnosis. PMID- 1603924 TI - Outbreak of food poisoning due to Salmonella typhimurium DT4 in mayonnaise. AB - In July 1989 a large outbreak of food poisoning (68 cases) occurred at a private club in Teddington (London Borough of Richmond-upon-Thames). Initial enquiries indicated that the peak of the outbreak occurred between 20th and 26th July. An epidemiological investigation (using self-completed questionnaires) was set up to determine the probable source of infection. Two groups among those exposed were selected: club staff (129), and cricket teams playing in a club tournament (105). Response rates were 89% and 64% respectively. Overall 50% (89) had gastrointestinal symptoms, including two hospital admissions. A highly significant association was found between illness and eating sandwiches containing mayonnaise. Microbiological investigations found Salmonella typhimurium DT4 in 36 of 68 faecal samples taken. This organism is not usually associated with food poisoning outbreaks. The probable source was identified as a flock of one of the egg suppliers. PMID- 1603925 TI - Organizing a project with community-based health agents recruited from prostitutes in Rio de Janeiro. PMID- 1603926 TI - Deaths from injury and poisoning of children in Liverpool: a ten-year survey 1978 1987. AB - Deaths of children in Liverpool under 16 years of age from injury and poisoning were examined for the period 1978-1987: 174 deaths occurred during the 10-year period. The commonest causes of death were road traffic accidents: 103 cases (60%). Of these 87 were of pedestrians struck by vehicles. Many of these children were very young and were unsupervised, or poorly supervised by other children. Drivers of vehicles were largely responsible for the accidents in 20 cases. The ability of children to cope in various traffic situations is discussed and responsibilities of parents and drivers are considered in relation to matters of accident prevention. PMID- 1603927 TI - The role of pharmacists in patients' education on medication. AB - The pharmacist, as the last health professional to come into contact with the patient, plays a vital role in patient education on drug use. The objective of this study was to assess the extent of pharmacists' involvement in the education of patients on drug use. Five hundred patients were interviewed. The findings indicated that both physicians and pharmacists explained the use of medication; however, pharmacists (20%) were much clearer in their instructions than physicians (11%). Ninety percent of patients who needed more information on their medicines, besides its frequency of use, did not receive it. Patients were not told about drug adverse reactions (100%), storage conditions (93%), important precautions (91%), drug-food interaction (90%) and preparation of suspensions (64%). Fifty-one respondents had in the past made mistakes in the use of their medications, and in 16% this resulted in serious consequences. Ninety-three prescriptions contained drug-drug interactions, and 97% of these were dispensed unnoticed. Of the patients interviewed, 72% were satisfied with the role of pharmacists in disseminating drug information, 67% would get a refill from them without going to their physicians, and 52% had consulted them for OTC medications. It is concluded that, although there are some deficiencies, pharmacists are providing information on drug usage and patients have confidence in them. They should, therefore, acquire the proper training and communication skills to enable them to provide this service more effectively. PMID- 1603928 TI - The prevalence of Toxocara canis ova in soil samples from parks and gardens in the London area. PMID- 1603929 TI - Prevalence of alcohol and drug use in a medical sciences campus freshman class. AB - A survey of alcohol and drug use in the freshman class of 1989-90 of the U.P.R. Medical Sciences Campus was conducted by means of a 55 item questionnaire. The instrument was completed by 73% of the enrolled freshman class (403 respondents). The data reflected that 64% of the surveyed subjects use alcohol; 47.4% being classified as occasional, 9.9% as moderate and 6.7% as heavy drinkers. Alcohol consumption by gender was 87.1% in males and 58.3% in females. Drug use was reported by 14.6% of all subjects. No gender difference was found in the distribution of drug users. Results were grouped by professional schools, analyzed and differences in use noted. Motivations for this alcohol and drug consumption were investigated, finding that approximately 50% did not fall under the usual categories like tension reduction and social approval. The desirability of further strengthening institutional prevention and educational efforts concerning the risk of alcohol and drug misuse by students is emphasized. PMID- 1603930 TI - Hepatic actinomycosis presenting as liver mass: case report and review of the literature. AB - Primary hepatic actinomycosis is an uncommon entity. We report the case of a young man with past history of an appendectomy who presented with fever, weight loss and a liver mass that was initially suspected to be neoplastic. Percutaneous liver biopsy revealed actinomyces-like organisms. The patient was treated with intravenous and oral penicillin with good therapeutic response. Review of the literature and correlation between hepatic actinomycosis and previous appendectomy are considered. PMID- 1603932 TI - The strange beginnings of diagnostic and therapeutic bronchoalveolar lavage. AB - Bronchoalveolar lavage was originally developed as a method for the diagnosis and treatment of pulmonary alveolar proteinosis. The first technique devised, "segmental flooding", was cumbersome but effective. Samples obtained provided information about the alveolar cellular response and alveolar protein dynamics. Most importantly, "segmental flooding" showed that living lung parenchyma was not damaged by repeated irrigation with isotonic saline as some had proposed. The therapeutic success and limitations of this first method of bronchoalveolar irrigation provided the intellectual stimulus which lead to the development of therapeutic whole-lung lavage. Serial whole-lung lavages, coupled with well-timed lung biopsies, offered the first opportunity to demonstrate in man the alveolar cellular response in a disease process, the dynamics of the production and dissipation of pulmonary lipids and the functioning of the surfactant system. The new and complex studies of the lungs' cellular reactions and metabolism may be better understood in the historical context of the first observations made possible by the development of bronchoalveolar lavage. PMID- 1603931 TI - Exogenous ochronosis. AB - Exogenous ochronosis is a condition characterized by hyperpigmentation of the face secondary to the use of hydroquinone-containing bleaching creams. Histopathologically, it presents a collection of yellowish-brown (ochronotic) globules in the papillary dermis. Two cases of exogenous ochronosis are reported, followed by a review of the literature. PMID- 1603933 TI - Activities of daily functioning and community adjustment of veterans in the VA residential care program. AB - This study was designed to identify the level of function in Activities of Daily Living (ADL) of veterans placed in the Personal Care Home Program (PCH) of the Department of Veterans Affairs Medical Center in Puerto Rico. At the same time, we explored how community adjustment was related to the veterans ADL functioning. It was an exploratory, descriptive, cross-sectional study of a random sample of 60 veterans placed in (32) Personal Care Homes. The Functional Independence Measure (FIM) was used to evaluate the veteran and determined his level of independence in ADL. The Community Adjustment Scale was used to assess adjustment behavior patterns of veterans at the personal care homes. Findings indicate the majority of veterans in the PCH program were elderly with a mean age of 64 years. They were functioning in a modified dependence level in ADL. They had made good to excellent community adjustment. No relationship between ADL level of functioning and community adjustment was found. PMID- 1603935 TI - [Advancements in computerized tomography. 2nd European Scientific User Conference. Berlin, 13-14 March 1992]. PMID- 1603934 TI - [XXXII Bailey K. Ashford Memorial Conference. Tropical sprue--revisited]. PMID- 1603936 TI - Can doctors rely on nurses' sponge counts? Case in point: Van Hook v. Anderson (824 P. 2d 509--WA (1992)). PMID- 1603937 TI - "Substantial evidence" criteria needed to uphold verdict on appeal. Case in point: Silvis through Silvis v. Hobbs (824 P 2d. 1013--MT (1992)). PMID- 1603938 TI - Biophysical aspects of neutron scattering from vibrational modes of proteins. AB - This review describes a major portion of the published work on neutron scattering experiments aimed at measuring large scale motions in proteins. The importance of these motions for enzyme function and oxygen transport is indicated. The theory applicable to each type of neuron scattering measurement is given and results are discussed with a view to biological relevance. New experiments are suggested and a comparison of neutron scattering data is made with results from other techniques such as raman scattering, infrared absorption, photolysis and molecular dynamics simulations. PMID- 1603939 TI - The voltage-activation of contraction in skeletal muscle. PMID- 1603940 TI - [Insect neuropeptides involved in its molt and metamorphosis]. PMID- 1603941 TI - [Protein translocation into isolated microbodies]. PMID- 1603942 TI - [Application of DNA fingerprint analysis to individual identification]. PMID- 1603943 TI - [Nuclear genome and polyploidy in wheat]. PMID- 1603944 TI - [Nuclear genome organization in Arabidopsis thaliana]. PMID- 1603945 TI - [Nuclear genome configuration of rice]. PMID- 1603946 TI - [Rearrangement of the nuclear genome]. PMID- 1603947 TI - [Mechanism of T-DNA integration into plant genomes and trial of plant gene targeting]. PMID- 1603948 TI - [Chloroplast genes and genome organization: their evolutional aspect]. PMID- 1603949 TI - [Transcription map of the chloroplast genome]. PMID- 1603950 TI - [Replication of chloroplast genome]. PMID- 1603951 TI - [Mitochondrial genomes in higher plants]. PMID- 1603952 TI - [Gene organization of mitochondrial genome from bryophte]. PMID- 1603953 TI - [The mitochondrial genome of green algae]. PMID- 1603954 TI - [Organization of the fungal mitochondrial genomes]. PMID- 1603955 TI - [Mitochondrial plasmids]. PMID- 1603956 TI - [Molecular basis of cytoplasmic male sterility in higher plants]. PMID- 1603957 TI - [Transcription machinery and its regulatory mechanism in plants]. PMID- 1603958 TI - [Transcriptional regulation of plant histone genes]. PMID- 1603959 TI - [Post-transcriptional regulation in plant gene expression-chloroplast RNA-binding protein]. PMID- 1603960 TI - [Molecular mechanisms for the sorting of proteins to the vacuoles]. PMID- 1603961 TI - [Photoregulation of gene expression]. PMID- 1603962 TI - [Regulation of the expression for the genes encoding heat-shock proteins]. PMID- 1603963 TI - [Regulation of plant gene expression by sugars]. PMID- 1603964 TI - [Nitrogen-dependent regulation of gene expression in plants]. PMID- 1603965 TI - [Regulation of plant defense gene expression]. PMID- 1603966 TI - [Regulated expression of the genes of pathogenesis-related proteins]. PMID- 1603967 TI - [Germination-genes induced by gibberellins]. PMID- 1603968 TI - [Gene expression during somatic embryogenesis]. PMID- 1603969 TI - [Molecular regulation of somatic embryogenesis]. PMID- 1603970 TI - [Auxin-regulated genes from tobacco mesophyll protoplasts]. PMID- 1603971 TI - [The genes involved in ethylene biosynthesis and their expression]. PMID- 1603972 TI - [Analysis of gene expression in cereal species]. PMID- 1603973 TI - [Molecular aspects of plant lipid metabolism]. PMID- 1603975 TI - [Gene expression during reproductive cell formation]. PMID- 1603974 TI - [Genetic regulatory systems of floral bud development]. PMID- 1603977 TI - [Gene regulation at the wx locus]. PMID- 1603976 TI - [Molecular mechanism of self-incompatibility in cruciferous plants]. PMID- 1603978 TI - [Regulation of genes in secondary metabolism]. PMID- 1603979 TI - [Regulation of seed storage protein gene expression]. PMID- 1603980 TI - [Clock genes of plants]. PMID- 1603981 TI - [Molecular mechanism of plant senescence]. PMID- 1603982 TI - [Determination of soluble interleukin-2 receptor in patients with American Trypanosomiasis in Panama]. AB - The quantitative determination of Inter leukin-2 Receptor (sIL-2R) in the serum of patients with acute or chronic Chagas disease is compared with values found in normal individuals. The mean value of soluble IL-2R in patients with acute Chagas' disease was found to be 3,282 +/- 171 U/ml. The mean value of sIL-2R in serum samples from chronic chagasic patients was 511 +/- 207 U/ml, while in the control or "normal" group of persons the mean value for sIL-2R was 366 +/- 108 U/ml. In patients with early or acute infections with T. cruzi, the serum levels of sIL-2R was usually above 1000 U/ml. However, the correlation with anti-T. cruzi antibodies and levels of sIL-2R was not always directly proportional. Specific antibodies anti-T. cruzi in serum from chronic chagasic patients, shown at low or high levels, did not reveal a proportional correlation with serum levels of sIL-2R which tend to be significantly lower than in early or acute infections. It is considered that high values for sIL-2R are related with the parasite activity and its pathologic interaction with the host. It is possible that high levels of sIL-2R could serve as an indicator of early or acute Chagas' disease and be useful in assessment of disease conditions and response to therapy. PMID- 1603983 TI - [Prevalence of deficiency of thyroxine-binding globulin (TBG)]. AB - During 3 years 1632 newborns from Gorgas Army hospital had their cord blood screened for congenital hypothyroidism by determining serum thyroxine levels (T4). Fifty-five had serum levels below 7 mcg/dl and 80% of them went into a confirmatory evaluation for hypothyroidism. Three of those (1.8/1000 live birth) had a familiar deficiency of thyroid binding globulin (TBG). All of them were male newborns born at 38 weeks of gestation. The average T4 from the umbilical cord was 2.4 +/- 1.3 mcg/dl. This value was significantly lower than the values from those with an initial T4 below 7 mcg/dl who did not have TBG deficiency. The prevalence of TBG deficiency in this study was about 10 times higher than the prevalence reported by other authors for both the general population and the male population. PMID- 1603984 TI - [Pulmonary hypertension in generalized lupus erythematosus]. AB - Two young women with systemic lupus erythematosus and pulmonary hypertension are reported. Both patients had Raynaud phenomenon and antibodies to cardiolipin. They seem to be potentially associated in the pathogenesis. Also, laboratory and hemodynamic findings were discussed. Although the treatment, the prognosis still bad. PMID- 1603985 TI - [Myocardial bridging as a cause of coronary insufficiency]. AB - The authors studied the clinical and angiographic findings in two patients who had a myocardial bridge (MB) in the right anterior descending coronary artery and did not have any arteriosclerotic lesions in the coronary arteries. The two patients were men, 57 and 58 years old. Both had a history of arterial hypertension (for 19 years and 6 months, respectively) and angina pectoris (for 7 years and 6 months, respectively). The resting EKG showed subepicardial ischemia in one and was normal in the other. The stress test was positive in both. Coronary artery angiography showed an MB in the right anterior descending coronary artery which caused a systolic constriction of 90% and 80%, 3 and 2 cm. long. Both patients had left ventricular hypertrophy. The authors conclude that MB is a frequent cause of coronary insufficiency and that the appearance of symptoms and their severity depends on the degree of systolic constriction, greater than 75%, and on the presence of left ventricular hypertrophy. The majority of patients are controlled with medical treatment and only a small number require surgical therapy. PMID- 1603986 TI - [Hepatic polycystic hydatidosis. Clinical and histopathologic report of the second native case of echinococcosis in the Republic of Panama]. AB - The second autochthonous case of hepatic hydatidosos by Echinococcus vogelli is reported for the Republic of Panama. The patient was a 8 year old female living in the Province of Colon (Maria Chiquita). She claimed never to have traveled outside panamanian territory. The multichambered cysts with fertile, numerous protoscolices were identified from biopsied material obtained after exploratory laparotomy at Manuel Amador Hospital in Colon (Republic of Panama). The cyst appeared multiloculated mostly affecting the left lobe of the liver, beside a cystic lesion on the right lobe. The large rostellar hooks, in a count of 100 protoscolices, had a total length of handles and blades which average 41 microns in diameter, which coincide with those of E. vogeli, the most prevalent hydatid disease in man in South and Central America. PMID- 1603987 TI - [Identification of emotional disturbances in the diabetic patient]. AB - The Emotional Adjustment Scale for Diabetics (EAD) and the Brown Scale (SB) were used to evaluate 60 diabetic patients. The aim of the study was to compare the clinicians' ability to diagnose the emotional maladjustment with the results of a standardized instrument. A battery of psychosocial tests was also applied. The results showed that SB has low sensibility, specificity and positive predictive value which suggests that clinicians has less ability to diagnose emotional maladjustment than a standardized instrument. The analysis of tests results helped to identify predictive variables for the results of SB (personality factors) and the results of EAD (locus of control of behavior, age, escolarity and scales D and F of the Minimult). The findings are discussed in the light of the relevant literature. PMID- 1603988 TI - [Breast cancer in a male. Report of a case]. AB - The authors studied the clinical history of a male patient, 51 years old, from Puerto Armeulles, Chiriqui, with the diagnosis of breast carcinoma, III A, who was treated with simple mastectomy and systemic cytotoxic therapy, with 5 FU, Adriamycin and Cyclophosphamide at three weeks intervals, completing six cycles, followed by radiotherapy to the tumor site and the areas of lymphatic drainage, and hormonal therapy with Tamoxifen. The patient is now in good health and without clinical, radiographic or enzymatic evidence of tumoral activity, twelve months after the diagnosis. PMID- 1603989 TI - [The first case of in vitro fertilization and embryo transfer in the Republic of Panama and Central America]. PMID- 1603990 TI - [The role of the radiologist in extracorporeal lithotripsy]. PMID- 1603991 TI - [Artifacts in echo-Doppler and color-Doppler]. AB - It is well known that artifacts can be observed during US examinations; the same is true also for Doppler and color-Doppler images of blood flow. Recognizing these artifacts is important to avoid image misinterpretations and, when possible, to overcome them by modifying either techniques or unit settings, or both. This work was aimed at presenting the several artifacts which can be observed during Doppler investigations, at classifying them, and trying to understand the physical and/or technical principles underlying their origin. Doppler and color-Doppler artifacts can be divided into four large groups: 1) artifacts regarding evaluation of the presence of flow; 2) artifacts regarding evaluation of the direction of flow; 3) artifacts regarding determination of the velocity of flow; 4) artifacts affecting spatial location, on the screen, of the examined vessel. Each of the above can cause severe diagnostic misinterpretations, if not correctly recognized and interpreted. It must be kept in mind that an accurate analysis of unit settings during scanning, and the meticulous evaluation of the obtained color images are of the utmost importance for the proper use of this valuable but difficult diagnostic technique. PMID- 1603992 TI - [Magnetic resonance angiography in the study of abdominal neoplasms. Preliminary experience]. AB - This study was designed to evaluate MRA imaging as a potential non-invasive method to study vascular infiltration in patients with abdominal neoplasms. Forty three patients with abdominal tumors proven by CT and/or MRI were examined with MRA and subsequently with angiography. Of 15 cases of liver tumor, MRA allowed poor intratumoral vascularization to be demonstrated in 1 patient only, but it always provided a characteristic sign--i.e., the complete absence of flow in the hepatic segments infiltrated by the tumor and the evidence of pericapsular neovascularization. In 8 cases portal vein involvement was observed (4 cases of compression/dislocation, 2 cases of infiltration and 2 of thrombosis). In all cases MRA allowed the relationship between tumor and venous structures to be evaluated. It also demonstrated collateral vessel formations in 8 patients with cancrocirrhosis. Two cases of thrombosis and 3 infiltrations of the vena cava were demonstrated. Neither hepatic artery nor intrahepatic arterial vascularization could be correctly evaluated. Of 10 cases of renal tumors and in 3 of adrenal tumors, renal vein infiltration was seen in 4 cases and compression in 3, with only 1 false-positive finding. In these patients and in those with retroperitoneal masses, MRA provided valuable information on the relationship between tumor and vascular structures and was useful in detecting collateral vessels. In our experience, MRA is to be considered as a complementary technique to be performed after CT or MRI when additional information is needed as to the relationship between tumor and vascular structures. In the preoperative evaluation of abdominal neoplasm, angiography remains the gold standard, in spite of its invasiveness. PMID- 1603993 TI - [Computed tomography and tumor markers as diagnostic alternatives to second-look surgery in the treatment of malignant ovarian tumors]. AB - Advanced malignant ovarian cancers are treated, after initial surgery, with first choice mono/polychemotherapy, the response to which is evaluated by means of second-look laparotomy. The poor prognostic value of second-look results, the incidence of false negatives, the lack of valuable second-choice therapies, and the high incidence of complications after repeated interventions, lead to the testing of diagnostic imaging modalities--especially CT and tumor markers (Ca 125 and Ca 15-3). To define their actual clinical value, CT and serum assays of Ca 125 and Ca 15-3 have been performed on 32 treated patients affected with ovarian cancers (stages II-IV), who were clinically free of disease. The results have been compared with second-look pathology, but especially with patient follow-up (min. 24 months). Second-look laparotomy yielded a high number of false negatives (9/22 = 41%); moreover, many important/severe complications were observed. Thus, its value appears to be questionable. CT exhibited high positive predictive value (76.9% over the 24-month follow-up); high for both Ca 125 and Ca 15-3 (100% respectively, at 24-month follow-up) thus, few false positives were observed. Moreover CT, having higher sensitivity (55.5%) than Ca 125 (11.5%) and Ca 15-3 (27.7%), has greater diagnostic capabilities, especially when the lesion is in extraperitoneal location. PMID- 1603994 TI - [Nonpalpable breast lesions. General considerations and a review of the literature in the light of the authors' own experience with 344 cases located preoperatively]. AB - The widespread use of mammography in breast cancer screening has increased the number of non-palpable breast lesions being detected in which the differential diagnosis between benign and malignant cases requires surgical biopsy. In order to remove these mammographically identified lesions the surgeon must be guided, which is why the techniques guiding the surgeon during lesions ablation have become most important. Accurate preoperative lesion localization must be done so that the excision can be complete and with the best cosmetic result. In this report we discuss localization methods, from the simplest to the most complicated ones. The commonest method has the advantage of employing no special instruments, and it is very simple, safe and fast. It requires a skilled hand and a little training. Instrumental methods are then discussed, from the simple dedicated compressor to the stereotactic techniques and, finally, the role of ultrasonography both in preoperative localization and in cytologic biopsy. The importance of mammographic examination of the surgical specimen is also stressed. PMID- 1603995 TI - [Echography of the operated breast]. AB - Aim of the present study is to evaluate the results of quadrantectomy by means of mammography and sonography (US). A hundred and thirty-five quadrantectomized patients bearing a carcinoma were investigated; 97 of them are now undergoing TCT. Mammographic examinations were performed with last-generation units; US studies employed high-frequency probes greater than or equal to 7.5 MHz. Ten relapses (7.4%) were observed, all of them around the scar: clinical examination correctly detected 3 cases, mammography 8, and US 6; the latter technique identified in 1 further case a pathologic finding which had not been previously assessed as a neoplastic lesion. Our results suggest that clinical examination has poor diagnostic value, while mammography has high value (8/10 cases), especially in detecting neoplastic microcalcifications (3/10 cases). The structural opacity of the breast caused 2/10 mammographic false negatives; US correctly detected 6/10 relapses, but failed to identify 3 microcalcifications. The combined use of the two techniques allowed the respective mistakes to be amended. US has proven to be especially useful not only to integrate mammography in the diagnosis of tumor recurrences, but also to study postoperative fluid collections, which are usually missed by mammography. PMID- 1603996 TI - [Echotomography in the diagnosis of bone tumors. Work in progress]. AB - Fifteen patients with positive conventional radiographs for morpho-structural neoplastic involvement of bone, were systematically submitted to US with a high frequency probe (7.5 MHz). US evaluation was aimed at testing, relative to conventional radiography, the sensitivity of the former technique in recognizing the main elementary signs of bone involvement--e.g., cortical interruption, periosteal reaction, and extraosseous spread. In 13 cases where conventional radiography had shown cortical bone involvement, US always confirmed the radiographic findings, showing cortical interruption in all cases and allowing a preliminary evaluation of lesion size in 10 cases. Morphological and structural alterations of bone profile--i.e., interruption or evident thinning of the hyperechoic line corresponding to the cortical profile--were the main and preliminary signs of pathologic skeletal involvement. US is suggested as a complementary and integrative technique to conventional radiology, because it allows elementary signs of morpho-structural alterations of the cortical bone to be identified, and a preliminary evaluation of tumor size to be made. PMID- 1603997 TI - [The direct and computed radiographic assessment of vertebral locations in children with acute lymphatic leukemia]. AB - The children affected with acute lymphoblastic leukemia (ALL) often exhibit secondary lesions of the spine. The diagnosis of spinal involvement is currently made by means of conventional radiography in postero-anterior and lateral views. The osteolytic lesions of the vertebral body present with collapse of the vertebral plates in a wide range of severity. Body evaluation is usually made by comparison with the adjacent vertebrae. Since leukemia is a systemic disease, several vertebrae are possibly involved in each case. In the attempt to develop a more sensitive method, which is less dependent on observers' evaluation, a quantitative and comparative analysis of vertebral bodies was performed. The radiographs in lateral view of the dorsal and lumbar spine of 14 children with ALL were analyzed: previous radiological reports suggested the lesion of one or more vertebral bodies. The area of each vertebral body was measured and digitalized by means of a backlighted graphic table and of a software developed to this purpose. The criteria to define the collapse of a vertebral body were the ratio between areas of adjacent vertebral bodies, in conformity to the anatomic and radiographic principle that, in the dorsal and lumbar spine, the body of a normal vertebra is equal to or bigger than that of the upper one. The data obtained by quantitative analysis were compared with conventional radiologic reports. A hundred and fifty-five vertebrae were analyzed by computerized analysis; 17 (10.9%) vertebrae, undetected at conventional analysis, were collapsed. This method allows a more precise diagnosis of collapsed vertebral lesions; its accuracy can be improved with further development of digital technology. PMID- 1603998 TI - [Echography in the study of the neonatal hip: the diagnostic-therapeutic implications of type-IIa (borderline) findings]. AB - Sonography (US) is a useful method in the early diagnosis of congenital hip dislocation; X-ray examination exhibits limitations due to high false-positive and false-negative rates. The advantages of US include: non-invasiveness, direct visualization of muscle and cartilage, dynamic demonstration of anatomical structures, and possible diagnosis in neonatal age. Therefore, US can be used as a screening or targeted diagnostic technique in selected newborns with clinical suspicion and/or risk factors. In this paper the authors report their experience in 1271 patients (721 females, 550 males), aged 1 day to 7 months, who were examined with US for the diagnosis of congenital hip dislocation. The newborns were divided into two groups at first examination: a) the screening group included 524 consecutive newborns (F = 266, M = 258) from S. Chiara Regional Hospital in Trento, and b) a selected group of 747 newborns (F = 455, M = 292) with clinical suspicion and/or risk factors, who had been selected in the Trento area. According to Graf's classification, the results of US in 2542 neonatal hips, were: 2346 (92.3%) normal hips, 171 (6.1%) type IIa hips, and 24 (1.6%) pathological hips. In the selected group (1494 hips) we observed: 1351 (90.4%) normal, 119 (8%) type IIa, and 24 (1.6%) pathological hips (IIb, IIc, D, III). In the screening group (1048 hips) we detected: 995 (95%) normal hips (Ia/Ib), 52 (4.9%) type IIa, and 1 (0.1%) pathological hips (D). Our experience suggests that US is a useful method in selected newborns with clinical suspicion of congenital hip dislocation and/or risk factors. US limitations consists in the dispersion of type IIa hips. Moreover, the need emerged for complete cooperation between pediatrician, radiologist, and orthopedist to optimize the cost/benefit ratio. PMID- 1603999 TI - [The magnetic resonance characteristics of rounded atelectasis]. AB - Rounded atelectasis is a peculiar form of lung collapse which is well known by radiologists. Its appearance on conventional radiographs and CT is by now well recognized and widely reported. Even though these two techniques usually allow a diagnosis to be made, the MR appearance of rounded atelectasis is worth mentioning as well. This diagnostic imaging technique is widely employed, and our experience suggests that, in some cases, MR Imaging can give an important contribution to the study of this condition. We report our experience with 6 cases of rounded atelectasis in 5 patients (one patient had bilateral lesions). Five signs characteristic of rounded atelectasis were observed: some of them are seen on both conventional radiographs and CT scans, others are typical of the latter technique. All cases showed peripheral location of the lesions and the "comet tail" sign--i.e., vascular structures gently curving into the mass. These two signs are also observed on conventional radiographs and CT scans. Typical of MR imaging are the extant 3 signs: low signal in T1 and high signal in T2 weighted images in the whole of our cases; no signal from pleural thickening next to the mass in T2-weighted images, and, finally, the "kidney-like" pattern--i.e., hypointense lines converging toward the center of the mass. All these signs, which were always observed in our series, support the current etiopathogenetic hypothesis of pleural effusion as an early sign, which is reported to be followed by fibrous pleural involution which wraps atelectatic parenchyma up. On the basis of these typical MR features a correct diagnosis can usually be made even in those cases in which conventional radiography and CT do not allow a definite diagnosis. PMID- 1604000 TI - [Intestinal transit studied with radiopaque markers in patients with multiple sclerosis]. AB - The patients affected with multiple sclerosis (MS) often complain of constipation. This symptom is little tolerated by the patient; its etiology is still unknown. MS patients often have their movements impaired by disease progress, so that they have to sit down for a long time, or else they exhibit severe problems walking or moving. MS patients also present low intraabdominal pressure during voluntary contraction of abdominal wall muscles. In these patients, the authors suggest to study intestinal transit time by means of radiopaque markers. To this purpose, the radiological follow-up contributes to the setting of colorectal MS dysfunctions by daily controls of the progress of per os radiopaque markers, focusing on colonic transit time and temporary deposit areas. The results show high incidence of anorectal constipation. Thus, the examination can be considered a useful tool in the study of MS dysfunctions and an effective alternative to anorectal manometry. PMID- 1604001 TI - [Tubal catheterization with selective salpingography in the diagnosis and therapy of fallopian tube obstruction]. AB - Fallopian tube catheterization with selective ostial [correction of osteal] salpingography is a new technique for the diagnosis of tubal factors of infertility and also for the treatment of proximal tubal occlusion (PTO). In this study, 246 women were considered, 20-42 years old, with primary or secondary infertility, who presented a unilateral or bilateral PTO at hysterosalpingography (HSG). Catheterization and selective salpingography have been successful in 93.9% of the cases. Failures (5.6%) have been ascribed to obstructive organic diseases, where it was impossible to overcome the stenosis with the catheter or the guide wire. Twenty-six spontaneous pregnancies were obtained (15 full-term deliveries) and 17 patients became pregnant after GIFT (13 full-term deliveries). At follow up, after 12 months 4 of 10 patients had normal tubes, while 6 patients presented a new unilateral or bilateral PTO. No major complications occurred; nevertheless, ectopic pregnancy is a possible event, because of the mechanically re-established patency in a nonfunctioning tube. PMID- 1604002 TI - [The "in situ" treatment of ureteral calculi with extracorporeal lithotripsy]. AB - The authors report on 80 cases of ureteral calculi treated with in situ extracorporeal shock wave (ESWL), with no retrograde or antegrade maneuvers. Success rate was high (97.5%). Forty-two calculi were located in the proximal ureter above the sacroiliac joint; 10 were in the pre-sacral ureter, and 28 in the pelvic ureter, below the inferior border of the sacroiliac joint. After ESWL, double-J stents were positioned in 5 patients and nephrostomy was performed in 4 cases with positioning of 7-F pig-tail catheters; 8 patients (10%) underwent additional post-lithotripsy urologic and radiologic examinations. Lithotripsy having failed in 2 patients (2.5%), surgery with ureterolithotomy was performed. In situ ESWL of ureteral calculi emerges from this trial as the treatment of choice and not as an alternative to urologic maneuvers or open surgery with ureterolithotomy: the latter methods are necessary only after ESWL failure. PMID- 1604003 TI - [Bone marrow transplantation with T-cell depletion and hyperfractionated whole body irradiation. The radiobiological and clinical correlations]. AB - Total body irradiation (TBI) and cyclophosphamide (Cy) is the conventional conditioning regimen for the patients who are to receive bone marrow transplantation (BMT). It is one of the most effective treatments for acute and chronic leukemias. In this paper we discuss the clinical and radiobiological features relative to TBI methods and to the kind of BMT. Graft-versus-host disease (GvHD) incidence is decreased by the depletion of T-lymphocytes from donor's bone marrow which causes high rates of rejection and relapses. Thus, more aggressive conditioning regimens are necessary than unmanipulated BMT. The results are also examined of different experimental and clinical trials on the immunohematological features of T-depleted BMT and the radiobiological behavior of normal and pathological target tissues due to different methods of TBI. We report the experience of the Perugia Bone Marrow Transplantation Unit and Radiation Oncology Service. We treated 54 patients suffering from acute leukemia (AL) and 34 cases with chronic myeloid leukemia (CML) with T-depleted allogeneic HLA-identical BMT. Three different conditioning regimens were employed in an effort to enhance cytoreduction and immunosuppression without significantly increasing extramedullary toxicity. TBI was administered according to a hyperfractionated scheme of 3 fractions a day for 4 days. The third conditioning regimen, including also thiothepa (TT), gave the best results in terms of stable uptake and leukemic cells eradication. Disease-free survival (DFS) is 55.5% in the patients with AL at a median follow-up of 40 months; in the patients with CML who were not treated with TT, DFS is 10% at a median follow-up of 60 months, while it is 66.6% at a median follow-up of 12 for the group of patients who received also TT. The conditioning regimen with hyperfractionated TBI, Cy and TT was effective and well tolerated; 12.5% of patients developed interstitial pneumonia. PMID- 1604004 TI - [Prostatic carcinoma: the importance of echographic monitoring of gland volume after radiotherapy]. AB - Prostatic volume modifications were retrospectively analyzed by means of serial endorectal US in 50 patients affected with prostatic adenocarcinoma previously submitted to external radiotherapy. A progressive reduction in glandular volume (of low, medium, and high grade) was observed in 48/50 patients respectively within 3 months, between 3 and 6 months, and 6-9 months after treatment. After 9 months only lesser modifications were observed. A statistically significant correlation (p less than 0.05) was found between volume decrease percentage and histologic grading of the tumor, but not with its stage. Within the groups of patients affected with similar-grade neoplasms, a statistically significant difference (p less than 0.05) was observed, relative to the decrease rate of prostatic volume, between the patients with complete response and those with partial or no response. US monitoring of prostatic volume after radiotherapy, if correlated with histologic grading, can yield early predictive elements as to treatment outcome, thus contributing to select non-responsive patients to submit to biopsy and, if necessary, to therapeutic alternatives or combinations. Longer term studies are needed to prove its effectiveness, to prognostic purposes, in the single patient. PMID- 1604005 TI - [Left ventricular systolic and diastolic asynchronism in patients with ischemic cardiopathy: its effects on ventricular filling]. AB - To assess whether left ventricular asynchrony would influence filling in coronary artery disease, 27 patients with coronary artery disease and 39 normal subjects were studied by rest radionuclide angiography. Lower ejection fraction and peak filling rate were found in the coronary artery disease group (56% +/- 17% versus 65% +/- 6%, p less than 0.05; 1.8 +/- 0.7 versus 2.9 +/- 1.4 end-diastolic volumes/s, p less than 0.05). Moreover, the patients with coronary artery disease had a prolonged isovolumic relaxation period (114 +/- 86 ms versus 70 +/- 43 ms, p less than 0.05). Two indices of left ventricular asynchrony were evaluated: the coefficient of variation of regional time to end-systole, and the coefficient of variation of regional time to peak filling rate. The coefficient of variation of regional time to peak filling rate was higher in the coronary artery disease group (10.1% +/- 10%) than in the normal subjects (6.2% +/- 3.7%, p less than 0.05). Both these parameters were inversely related to global peak filling rate in the coronary artery disease group. These findings suggest that in patients with coronary artery disease left ventricular systolic and diastolic asynchrony plays a role in determining left ventricular diastolic properties. PMID- 1604006 TI - [Scurvy: a disease that has not yet disappeared. Apropos a case]. PMID- 1604007 TI - [The echo-Doppler diagnosis and embolization treatment of a dural arteriovenous malformation]. PMID- 1604008 TI - [Neuroblastoma metastasis to the falx cerebri. A case report]. PMID- 1604009 TI - [The mandibular location of an osteoid osteoma. A case report]. PMID- 1604010 TI - [The CT findings in a case of nonobstructive multifocal mucoid impaction]. PMID- 1604011 TI - [The polysplenia syndrome. A report of a case in an adult]. PMID- 1604012 TI - [A rare form of neoplasm of the stomach wall: neurofibroma. A case report]. PMID- 1604013 TI - [Unusual clinical and radiological findings in drug-induced hepatopathy]. PMID- 1604014 TI - [Malignant pelvic schwannoma. Its diagnosis by US-guided transrectal needle biopsy]. PMID- 1604015 TI - [The importance of the correct assessment of artifacts in echotomography]. PMID- 1604016 TI - [Fractures of the humeral shaft: role of fasciculated nailing using Hackethal's method. Apropos of 129 cases]. AB - This retrospective study was based on 141 diaphyseal fractures of the humerus, treated by Hackethal fasciculated pinning, among 371 fractures followed up during 10 years in our department. There were six preoperative radial paralyses. The mean consolidation delay was 65 days. Six fractures did not unite and there was no sepsis. The only immediate neurological postoperative complication was a regressive cubital paralysis. 72 fractures could be followed-up with a mean of 4 years, to establish a functional result chart. 94.4 per cent of the results were good and very good, 2 shoulder stiffness and only one elbow stiffness. The displaced fractures of the humeral diaphysis on D2 to D5 zones, as well as pathological fractures are good indications for Hackethal fasciculated pinning. PMID- 1604017 TI - [Recent fractures of the humeral shaft in adults. Role of surgical treatment using screwed plates. Apropos of 35 cases surgically treated]. AB - Thirty five cases of recent fractures of the adult humeral shaft were treated by using A0 plating technics. Most of the results were satisfactory (91 per cent of good and excellent results). A few post-operative complications were observed: two deep infections, one radial nerve palsy, no pseudarthrosis. Once indicated, internal fixation using plating is the best surgical technic for the authors of the present study. PMID- 1604018 TI - [Value of puncture-arthrography in the diagnosis of infection of total hip arthroplasty]. AB - Arthrography with hip aspiration was performed in 143 patients with hip arthroplasties to determine its effectiveness as a technique for diagnosing infection. Thirty-three cases of infection were found. On 26 occasions the germ responsible was isolated in the joint fluid. In six other cases infection was revealed from cytologic or arthrographic findings, or from both. Only once was a diagnosis of infection not arrived at. In this series of patients, except in cases of evolutive inflammatory rheumatism, cytologic examination of the joint fluid was a discriminative factor in diagnosis. Hip aspiration arthrography had a sensitivity of 79 per cent for the diagnosis of infection in arthroplasty with isolation of the germ and a specificity of 100 per cent. The sensitivity of the diagnosis rose to 91% when any one of the following features was observed: leucocytosis of the joint fluid higher than 10,000 elements/mm3; presence of a fistula or of fistulization on arthrography; isolation of the germ in the joint fluid or the rinsing liquid. PMID- 1604019 TI - [Long-term outcome of pectus excavatum surgically treated in children]. AB - The authors have studied the result of 34 pectus excavatum, corrected by two surgical methods, followed up between 3 and 20 years: half of cases were treated by Judet's procedure, making turn over of anterior wall chest, with 35 per cent of good result. The other cases were treated by sternochondroplasty and internal fixation, with 88 per cent of good result. Early failures related to sternal non union and to infection, occurred in 53 per cent of Judet's procedure; eight of the 13 failures were managed by sternochondroplasty (7 cases) and Judet's procedure (1 case); followed by good results. Failure at further time was related to the young age of the patients at treatment, to the deficiency of fixation and early removal of material. Consequently, durable correction at long term was obtained, when treatment was performed by sternochondroplasty procedure, over 14 years of age, when many pins were used for fixing the correction, left in place for more than one year. In such cases, we didn't observe regression of result. When small residual deformities subsisted they were often masked by the development of the muscles in man, and breast in woman, providing acceptable aspect of chest. PMID- 1604020 TI - [Fracture of the femoral neck complicating algodystrophy of the hip during pregnancy. Apropos of 2 cases]. AB - The authors report 2 cases of fracture of the femoral neck in pregnant women. This is a serious complication of a poorly understood disease, algodystrophy of the hip during pregnancy (transient osteoporosis of the hip of pregnancy, as referred by Anglo-saxon practitioners), whose main clinical, paraclinical and course characteristics are reported. The risk of subcapital fracture is maximal during the period of term, justifying recumbency in painful forms. In spite of the phantom appearance of the femoral head and neck, this type of fractures should not be confused with tumoral osteolysis, since they always unite within usual intervals. PMID- 1604021 TI - [Treatment of old or recurrent ruptures of the patellar ligament by contralateral autograft]. AB - Patellar ligament ruptures are difficult to treat, and require transfer of good quality tissues for an effective reconstruction. In this study the contralateral patellar ligament was chosen in preference to other types of graft. A graft was taken from the opposite knee (length 16 cm, width 8 mm) composed of a block of tibial bone, middle third of patellar ligament, block of patella, and quadriceps tendon. The bone blocks were embedded in slots made on the anterior surface of the patella and the tibia. The method of fixation allowed exact positioning as regards the patella height, and was sufficiently strong to allow immediate mobilisation and full weight-bearing. A series of 13 knees was operated on between October 1988 and July 1990, with a mean post-operative follow-up of 8.6 months. The technique was used twice following total patellectomy and once following total knee arthroplasty. This operation, without any complications from the donor site, produced a stable knee, corrected the extensor lag, and resulted in a mean post-operative flexion of 91 degrees. PMID- 1604022 TI - [Ambulatory orthopedic surgery. A retrospective study apropos of 2338 cases]. AB - A retrospective study of 2,338 outpatient surgical procedures performed at the Centre Hospitalier de l'Universite Laval was undertaken. There were 1,308 men and 1,030 women, with a mean age of 40.7 years. General anaesthesia was used in 91.5 per cent of the cases. After surgery, the patients were discharged according to the criteria described by Wetchler and Kortilla. The unanticipated hospital admission rate was 6.1 per cent and the complication rate was 1.3 per cent with no life threatening conditions. Proper selection and preparation of the patient, severe criteria for safe discharge after Day Surgery are mandatory for the patient's safety and satisfaction. PMID- 1604023 TI - [Roger Sohier 1903-1991]. PMID- 1604024 TI - Determinants of perinatal and infant mortality in Italy. AB - Determinants of stillbirths, perinatal and infant mortality in Italy have been analyzed using information collected routinely by the Italian Central Institute of Statistics on more than 2,400,000 births and 33,000 infant deaths in the period 1980-1983. Individual records included data on maternal (i.e. age, education, obstetric history) and fetal characteristics (sex, birth weight, gestational week at birth). The Italian stillbirth, perinatal and infant (1st 365th day of life) mortality rates in the period considered were respectively 7.7/1000 births, 16.4/1000 births and 13.5/1000 livebirths. Perinatal and infant mortality was extremely elevated in the very-low-birth-weight category. About 90% of liverbirths weighing less than 1000 g died within the first year of life, but this fell to about 45% in babies weighing 1000-1499 g. Among other factors, stillbirth, perinatal and infant mortality rates were elevated among males, born to older women and in higher birth rank and multiple pregnancies. These findings persisted, although less markedly, after adjustment for weight. Mortality rates were about 50-70% higher in less educated women. This finding was not markedly changed after adjustment for birth weight and maternal age, suggesting that socio economic factors are per se important determinants of perinatal and infant mortality in Italy. PMID- 1604025 TI - [Epidemiological surveillance of nursery school children in the Herault for the evaluation of maternal and infant health and welfare services]. AB - A random sample of 4-5 years old children born in the same year was taken from the infant schools of the Herault (France) and examined by pediatricians during a systematic check carried out by the Mother and Child Protection Department of the Health Service. This gave and estimation of the prevalence of the most widespread health problems: language, motricity, eyesight, hearing, obesity and asthma. Differences according to social and familial factors were found for language and motricity problems, as well as for access to preventive care. PMID- 1604026 TI - [Statistic modeling of geographic and epidemiologic variations]. AB - In epidemiology, studies of the geographical variations of mortality or incidence rates for some chronic diseases have often given rise to etiological clues concerning those diseases. In this framework the variables concerned have a spatially autocorrelated structure which has to be taken into account in the statistical analysis. The statistical techniques used to study in the first place the spatial variations of mortality rates and then the joint geographical variations of mortality and exposure indices are reviewed. Emphasis is placed on the importance played by the geographical scale of the analysed data in the modelling process as well as on the interpretation problems of geographical correlation studies. PMID- 1604027 TI - [Value of utility measures: recurrent respiratory infections]. AB - Medical decisions have to integrate not only the clinical dimension of a disorder, but also all the repercussions of the therapeutic strategy on the patient's life. Various techniques may be used to identify the preferences of a subject, by estimating the relative utility associated with different states of health. One of these techniques, the "standard gamble", enabled us to determine the utility that patients with recurrent respiratory infections associate with the results of various therapies. The findings show that this utility is not a linear function of therapeutic results. They also show that when the number of years of lost life is calculated, the loss due to alteration of the quality of life linked to the frequency of acute episodes is not obstructive pulmonary disease. PMID- 1604028 TI - [The exact costs of studies in a hospital nuclear medicine department]. AB - Objective data about the costs of nuclear medicine examinations are scarce and rather conflicting. Authors describe a method quantitating the costs of nuclear medicine investigations. These calculations were applied to a medium-sized nuclear medicine center set up in a teaching hospital. Calculations were as a tarification and followed the rules of monographic studies. They rely on exhaustive evaluation of each expense and precise analysis of their repartition. Average cost of the examination was 1,016 FF but the study reveals that costs varied from 664 to 6,746 FF. It appears that, but the more common investigations, exact costs are poorly related with nomenclature codification and that radiopharmaceutical costs have to be separately dealt with. This method allows to simulate costs-effects of any structure modification before being applied. One of the major feature of such a study is that it depicts a given center at a given time. Although it is to be hoped that the method should be spread, it should be hazardous to generalize its results. PMID- 1604029 TI - Height and the prevalence of chronic disease. AB - The relationship of stature with the prevalence of 18 chronic diseases or groups of diseases was analysed using data from the 1983 Italian National Health Survey, based on a sample of 63,859 individuals aged 20 or over randomly selected within strata of geographical area, size of the place of residence and of the household in order to be representative of the Italian population. Rate ratios (RR) were computed using multiple logistic regression, including terms for sex, age, geographical area, education and smoking. For 15 out of 18 diseases or groups of diseases the RR was below unity in the highest quartiles of height, and the inverse trends with stature were significant for 11 (diabetes, RR 0.90 for highest vs lowest quartile; heart disease, RR 0.92; chronic bronchitis and emphysema, RR 0.84; bronchial asthma, RR 0.70; anaemias, RR 0.70; liver cirrhosis, RR 0.62; urolithiasis, RR 0.76; renal insufficiency, RR 0.71; arthritis, RR 0.89; psychiatric and neurological disorders, RR 0.82). None of the diseases considered showed significant direct trends with height, but hypertension (RR 1.09 for the highest vs lowest quartile), haemorrhoids or varices (RR 1.09) and cancers (RR 1.22) tended to be elevated in the highest quartile of height. The generalised inverse relationship between height and prevalence of chronic disease suggests that poorer nutrition in childhood and adolescence is an unfavourable indicator for the subsequent occurrence of several diseases. Major exceptions were hypertension and varices, two conditions highly dependent on the pattern of health care utilization, and cancer. PMID- 1604030 TI - [The principal statistical software useful in biomedical research with microcomputers]. AB - The authors describe pragmatic aspects of the use of the main statistical software packages for biomedical research with microcomputers. Data analysis and management facilities and some technical and commercial features are comparatively indicated. PMID- 1604031 TI - Dissonant smoking in the European Community. PMID- 1604032 TI - [The cardiology consultation in a health-service area hospital. The clinical aspects and the demand for diagnostic procedures]. AB - Four consecutive years (1987-1990) outpatients attendance at a cardiology clinic was recorded in a district hospital with a catchment area of 200,000 inhabitants. The aim being to identify and evaluate the demand for cardiology consultations. A system for recording diagnoses was developed, based on the WONCA. The total number of consultations was 26,273, 27% being new patients, 78% of whom were referred by family doctors and health centers. Of the total, 57% were male. The most common age groups being from 60 to 69 (25%) and from 50 to 59 (23%); 22% were over 69. In 13.7% of the consultations, the find diagnosis was of "healthy hearts", in 16.7% valvular heart disease, in 31.5% ischaemic heart disease, in 15.1% arrhythmias, in 8.4% hypertension, and the remainder were other diseases. We carried out 4,406 echocardiograms, 1,408 exercise tests and 511 Holter monitoring traces. There were 322 direct hospital admissions, and 6,094 discharges in the four years period. We consider this type of records to be useful organizing cardiology outpatients clinics, analyzing the demand, and planning the use of health care resources, as well as estimating future needs and assessing quality of care. PMID- 1604033 TI - [The performance of transesophageal echocardiography in clinical cardiovascular practice]. AB - The usefulness of transesophageal echocardiography (TEE) in cardiovascular clinical practice is assessed. Seven hundred transesophageal studies were performed between November 1989 and October 1991. One hundred and seventeen studies carried out during the follow-up of treated non-acute pathologies were excluded. The study could not be made in 6 patients. The most frequent indications of TEE were aortic pathology study, 120 (21%), infective endocarditis, 72 (13%), origin of systemic embolisms, 66 (11%), and mitral pre valvuloplasty and intensive care, 64 (11%). The incidence of pathologic findings on TEE not diagnosed by conventional echocardiography was 32% (182/577). The incidence of pathologic findings with therapeutic implications was 15% (85/577). Indications showing a greater incidence of pathologic findings with therapeutic implications were: 1) thoracic aorta pathology, 42 (35%); 2) mitral prostheses disfunction, 8 (19%), and 3) mitral pre-valvuloplasty, 10 (16%). Infective endocarditis, intensive care studies and congenital cardiopathies had an incidence of 12%. TEE findings in the study of intracardiac masses, the origin of peripheral embolisms and mitral insufficiency had little influence (less than 5%) on the management of the patient. PMID- 1604034 TI - [Transluminal percutaneous coronary angioplasty of the left coronary artery]. AB - This paper describes our preliminary experience with left main coronary angioplasty in 8 patients (9 procedures). In 6 patients the left main coronary artery was "protected" either by previous by-pass surgery (4 patients) or by collateral vessels from the right coronary artery (2 patients). Three patients had a total occlusion of the left main coronary artery and 2 of them had a recent or acute myocardial infarction and the coronary angiogram suggested a thrombotic occlusion of the infarct-related artery. Three patients were not considered surgical candidates and an additional patient, who was in cardiogenic shock, required an emergency coronary angioplasty as "rescue" procedure. A successful dilatation was achieved in 6 patients (including a patient with successful deployment of a Palmaz-Schatz stent) but, unfortunately, one them eventually died 7 days later from a femoral sepsis related to the procedure. However in the 2 remaining patients--with a total occlusion of the left main coronary artery in relation with a myocardial infarction--the dilatation procedures were unsuccessful. One patient underwent a successful repeat coronary angioplasty for restenosis of left main coronary artery. Our preliminary experience confirms previous reports suggesting the value of coronary angioplasty in patients with left main coronary artery disease providing a careful selection of possible candidates is performed prior to the procedure. PMID- 1604035 TI - [Angioplasty of the left main coronary artery. Has something changed?]. PMID- 1604036 TI - [Rupture of the middle left ventricle after a mitral valve replacement. A report on 27 autopsy cases]. AB - Left ventricular rupture is a serious complication of mitral valve replacement. The prevalence ranged from 0.5 to 14%, and is the principal cause of early postoperative death following mitral valve replacement. In this report we described certain morphologic observations and some clinical and epidemiological data of a series of 27 necropsy patients with midventricular rupture (type III). This complication was predominantly present in females (88.9%) with an average age of 44 +/- 11.4 years. The predominant valvular lesion was stenosis (70.4%). In all cases we found small-sized left ventricles and the ventricular wall hypertrophied. Perforation was observed in the 18.5% of the cases. In 59.2% of the patients high profile prostheses were used. Seventy-eight percent of patients died before 24 hours with refractory ventricular failure and only in the 25.9% of cases the clinical diagnoses was suspected and rupture unsuccessfully repaired. Our results suggested that age, sex, type of mitral lesion, ventricular size and type of prostheses are not risk factors for this complication. The mortality is high and the diagnosis was not suspected frequently. Midventricular rupture of the left ventricle is a lethal complication and is necessary to know all its characteristics to implement better methods of prevention and management. PMID- 1604038 TI - [Chronic heart failure (IX). Dilated myocardiopathy and the problem of diagnosing myocarditis. A proposal for settling the debate]. PMID- 1604037 TI - [The 2-chambered right ventricle with an anomalous muscle bundle]. AB - The clinical picture, course, electrocardiogram and chest X-Ray of 30 patients with the angiocardiographic diagnosis of double-chambered right ventricle, along with the echocardiogram in 18 and surgical results in 26 are analyzed. A ventricular septal defect was associated in most of the patients, that had spontaneous closure in some of them. The clinical picture and serial catheterization in some cases suggested progressive obstruction of the right ventricular outflow tract. In this, as in most of the reported series, the history, physical examination, ECG and roentgenogram were inconclusive for diagnosis of this entity. Two-dimensional echocardiography was the most reliable non invasive method to assess this malformation, even superior to catheterization in some aspects. The angiocardiographic findings are quite distinctive, allowing differentiation of other types of subpulmonary stenosis. In order to achieve a good surgical result is essential a precise diagnosis of this malformation and of the associated anomalies. The long-term prognosis was good as in most of the reported series. PMID- 1604039 TI - [Macro CK type 2 as a cause of a false increase in CK-MB]. AB - A case of CK-MB falsely elevated activity due to the presence of a macro CK is reported. The MB quantification showed inferior levels to the pre-established cut off. The CK isoenzymes electrophoresis showed a type 2 macro CK. We suggest carrying out CK isoenzyme electrophoresis of CK-MB quantification in those cases in which the clinical course or ECG changes do not correlate with the CK-MB values, and in cases presenting low whole CK activity values along with high CK MB values. PMID- 1604040 TI - [Spontaneous remission in a patient with long-term idiopathic dilated myocardiopathy]. AB - The case of a patient with long-term idiopathic dilated cardiomyopathy, functional class IV, very depressed left ventricular ejection fraction (13%) and history of severe dyspnea for more than four years, who experienced an spontaneous clinical and hemodynamic recovery (functional class I, left ventricular ejection fraction 51%) while being on waiting list for heart transplantation is reported. The patient remains in good clinical condition after a follow-up of two years. PMID- 1604041 TI - [Spontaneous calcific embolization in calcified aortic valve stenosis. A case report]. AB - Calcific embolism from an aortic stenosis is an uncommon event that can be seen after cardiac surgery or left heart catheterization but extremely rare in a spontaneous way. We report a case of a patient with calcified aortic stenosis presenting a spontaneous calcareous embolism in the retinal artery. We review the literature about this problem as well. PMID- 1604042 TI - Effects of dopamine on renal receptors for arginine vasopressin. AB - To determine whether dopamine would affect the arginine vasopressin (AVP) receptors in the kidney, and if so, which source of dopamine would predominantly affect them, changes in the AVP receptors of the rat kidney were measured under the conditions of chronic renal denervation and the chronic infusion of dopamine using the radiolabeled receptor assay (RRA) of [3H]-AVP. Denervation was performed by stripping the nerves from the renal artery and coating them with 10% phenol. Chronic denervation had no significant effect on either the affinity or maximum binding capacity of the renal AVP receptors, although diuresis was observed. The chronic infusion of dopamine using an osmotic minipump produced a decrease in the affinity of the AVP receptors. These observations indicate that dopamine may regulate the AVP receptors in rat kidney via circulating dopamine. PMID- 1604043 TI - Bioavailability of ibuprofen from oral and suppository preparations in rats. AB - Bioavailability of ibuprofen (15 mgkg-1) from oral and suppository dosage forms was investigated. Three different combinations of PEG 4000 and 1000 and theobroma oil were used as suppository bases. Oral administration gave higher values for mean residence time (MRT) and absolute bioavailability (F) compared to suppository dosage forms. The theobroma oil base was associated with lower maximum plasma concentration (cpmax), area under the concentration time curve (AUC) and F values compared to the other bases but differences were not significant (P greater than 0.05). Ibuprofen appears to be strongly retained by the lipophilic base, thereby limiting its diffusion through the rectal mucosal membrane. The absorption profile was slightly improved for the three PEG combination bases but were inferior to oral dosing. It is suggested that the relatively smaller size of the rectal mucosal membrane compared to the small intestine was primarily responsible for limiting the rate/extent of ibuprofen absorption. The absorption profile from the suppository preparations may be enhanced by the appropriate selection of the bases and their additives. PMID- 1604044 TI - Effects of chloral, chloralose and pentobarbitone on monoamine and (neuropeptide Y) NPY levels in various tissues in the rat. AB - Sampling of blood or tissues in experimental animals need frequently a general anesthesia. Some anesthetic agents are known to modify plasma levels of catecholamines; moreover NPY is co-released with noradrenaline or adrenaline under certain conditions. Thus, we investigated the effect of three general anesthetic agents, chloral, chloralose and pentobarbital (pentobarbitone) on the levels of monoamines and NPY in rat hypothalamus, medulla, atria and adrenals. Monoamines were analysed by high pressure liquid chromatography using an electrochemical detection and NPY was measured by radioimmunoassay (immunoradiometric assay, IRMA). Chloralose or pentobarbitone did not affect monoamine tissue levels. In contrast, chloral increased 5-hydroxyindolacetic acid and to a lesser extent serotonin levels in the hypothalamus. NPY tissue levels did not change whatever the anesthetic used. These results must be taken into account in pharmacological or toxicological studies which need the use of a general anesthesia. PMID- 1604046 TI - Depression of hepatic drug metabolism in endotoxin-treated and sarcoma-bearing mice. AB - The effect of a single dose of bacterial endotoxin (lipopolysaccharide, LPS) was compared with that of tumor implantation in mice on the activity of several hepatic cytochrome P-450-dependent monooxygenases. These included ethoxycoumarin O-deethylase, p-nitrophenol hydroxylase, aminopyrine N-demethylase, pentoxyresorufin O-depentylase, ethoxyresorufin O-deethylase and testosterone hydroxylase. For this purpose, mice were treated i.p. with 5 micrograms of LPS or implanted in the right paw with S 180 sarcoma. A comparable depression (30-50%) of total microsomal P-450 content as well as of the different P-450 monooxygenase activities tested was observed in LPS-treated mice (24 h after LPS) and in tumor bearing mice (12 days after implantation). The lack of differences in the pattern of depression of microsomal enzymes between LPS-treated and tumor-bearing mice suggests that a common mechanisms might be involved in the depression of P-450 by LPS or S-180 implantation. PMID- 1604045 TI - Toxic response to repeated oral administration of 2-chloroethyl linoleate in rats. AB - In the present study, we investigated the toxic response to repeated oral administration of 2-chloroethyl linoleate (2-CEL) in male rats at 250 mg/kg body weight for 2 weeks on alternate days (total 7 doses). Control rats received an equal volume of mineral oil. The five animals from each group were sacrificed on days 1, 7 and 28 following the last dose. No significant changes were observed in body weight, as well as organ-to-body weight ratios due to 2-CEL treatment. The red blood cell counts increased significantly in 2-CEL treated animals at day 28 as compared to the controls. Elevated counts of platelets, monocytes and eosinophils and low counts of basophils and large unstained cells were also observed at some time points in 2-CEL treated rats. Significantly reduced activities of total serum lactate dehydrogenase (LDH), aspartate aminotransferase and alanine aminotransferase were found at most of the time points except for LDH at day 28. Adenosine triphosphatase activity was also significantly reduced in liver mitochondrial fraction at all time points. Histopathological studies showed consistent centrilobular lesions (incidence 4/4) in the liver consisting of hepatocyte vacuolar degeneration and focal necrosis at day 28. A few centrilobular lesions were also observed (incidence 2/4) at day 7, while no changes were observed at day 1. These results indicate that 2-CEL is a hepatotoxin, however, the observed decrease in serum enzyme levels in relation to hepatotoxicity of 2-CEL, needs to be elucidated. PMID- 1604047 TI - Copper metabolism in new mutant Long-Evans cinnamon (LEC) rats causing hereditary hepatitis: gastrointestinal absorption and distribution of radioisotopic copper (64Cu). AB - Long-Evans cinnamon (LEC) rats 60 days old showed a concentration of 127.7 +/- 10.9 micrograms/g of Cu in the liver, compared to 1.6 +/- 0.1 micrograms/g in Fischer rats 60 days old. At 2 hr after an oral injection of 64Cu, total retention of 64Cu in the whole blood, liver and kidneys was 16.8 +/- 3.4% of the dose in LEC rats, compared to 13.1 +/- 1.3% in Fischer rats. The recovery rates of retained-64Cu in the livers in LEC and Fischer rats were 82% and 59%, respectively. More than 90% and about 60% of hepatic 64Cu existed in the cytosol fraction in LEC and Fischer rats, respectively. Furthermore, more than 90% of the cytosolic 64Cu was found as MT in LEC rats. In Fischer rats, this proportion was about 60%. In the duodenum mucosal cytosol fraction from LEC rats, about 50% of 64Cu was bound to metallothionein (MT) protein. In Fischer rats, this proportion was less than 20%. When a 64Cu compound was intraperitoneally injected, 70% and only 15% were recovered in the liver 20 hr after the injection in LEC and Fischer rats, respectively. Furthermore, LEC rats showed very low 64Cu activity in the serum, and their duodenal activities were slightly low compared to Fischer rats. These results suggest that the gross accumulation of hepatic Cu is mainly due to deficient excretion of Cu from the liver. PMID- 1604048 TI - Sustained release of 5-fluorouracil from oil/water emulsions. AB - Release profile of 5-fluorouracil (5-FU) from O/W emulsion and bone marrow toxicity of 5-FU to mice were compared with those of an aqueous solution of 5-FU. 5-FU emulsion had lower bone marrow toxicity and a slower drug release rate than the 5-FU aqueous solution which exhibited high bone marrow toxicity and fast drug release rate. A correlation between the rate of drug release and bone marrow toxicity was suggested. PMID- 1604049 TI - Early endotoxin tolerance in suckling rats. AB - Early endotoxin tolerance has not been well investigated in the newborn. This study demonstrated that a sublethal dose of Salmonella enteritidis lipopolysaccharide (S. ent-LPS) or rough mutant Salmonella minnesota LPS (Re-LPS) induced early endotoxin tolerance in suckling rats, showing blunted hypoglycemia and decreased mortality. The mortality of endotoxic shock was lower in S. ent-LPS pretreated group than Re-LPS pretreated group. A sublethal dose of S. ent-LPS caused lactacidemia but Re-LPS did not. Therefore, early endotoxin tolerance appeared to be related to physiologic responses to the initial LPS exposure. PMID- 1604051 TI - Special issue in honor of Professor Pierre Dejours. PMID- 1604050 TI - Effect of repeated administration of chelating agents on distribution, excretion, and renal toxicity of gold sodium thiomalate in rats. AB - The effects of the repeated administration of D-penicillamine, 2,3 dimercaptosuccinic acid, 2,3-dimercaptopropane sulphonate, and N-(2-mercapto-2 methylpropanoyl)-L-cysteine 24 h after gold sodium thiomalate (AuTM) injection on the distribution, excretion, and renal toxicity of gold in rats were investigated. Three i.p. injections of these chelating agents (1.2 mmol/kg) at 1, 3, and 5 days after AuTM injection (0.026 mmol/kg) removed gold from kidney and liver through urinary and fecal excretion, and protected against the renal damage induced by AuTM. These findings indicate that these compounds are useful antidotes for gold toxicity. PMID- 1604052 TI - Funding biomedical research: a common ground for concern? AB - Despite record levels of support, concerns over the ability of individual investigators to obtain funding for their research have been growing within the biomedical research community. The concerns have been focused almost exclusively upon the outcomes of funding decisions, and have ignored the pressures that produce them. Yet, it is those pressures that constitute our 'common ground for concern'. Resources committed in response to the pressures from special interest groups are unavailable for general competition based upon scientific merit. We in the biomedical research community must recognize that such self-interested efforts to dedicate resources undermine the integrity of the existing processes for making funding decisions. As a community, we should instead attempt to ensure that adequate resources are available to support the best quality research. PMID- 1604053 TI - Personnalite ventilatoire--an overview. AB - An infinite number of possible combinations of tidal volume and breathing frequency, as well as pattern of airflow, can achieve the alveolar ventilation required for normal gas exchange. Individuals appear to select one particular pattern. This paper summarises our work relating to differences in the pattern of breathing between individuals when at rest and discusses the possible determinants of such individuality. PMID- 1604054 TI - Analyses of human respiratory flow patterns. AB - Respiratory drives follow various afferent pathways to the respiratory centres; nevertheless, steady-state breathing patterns described in terms of tidal volumes and phase durations are largely independent of the nature of the respiratory stimulus. Flow has now been recorded during steady states from six subjects in rest and hyperpnoea induced by exercise, and hypercapnia in euoxia and in hypoxia (asphyxia). Flow patterns from different stimuli were compared isopnoeically. Quantitative methods allowed the patterns to be described in terms of several variables. The consistent small differences in isopnoeic flow patterns were: In asphyxia, the initial inspiratory acceleration was greater than in hypercapnia, and the peak flow was reached earlier. In exercise the peak flow occurred later in inspiration, and the expiratory flow was maintained high until nearer the end of the phase than with the chemical drives so that the flow pattern was less angular in shape. Stimulus-dependent effects, obvious during transient changes, are greatly attenuated rather than absent in steady states. PMID- 1604056 TI - Variations in function and design: testing symmorphosis in the respiratory system. AB - We explore the question of whether and to what extent the large variation in energy requirements observed among mammals is related to variations in the design of the respiratory system, from the lung to the mitochondria in muscle cells. Resting metabolic rate is determined by body size (allometric variation). Maximal rates of O2 consumption (VO2 max) also vary in a regular manner with body size, but adaptive variation allows some species to achieve much higher values than others of the same body size. We, therefore, consider adaptive variation as modulation of structures and functions above those determined by allometric variation. A model is presented that separates functional and design parameters at four steps of the respiratory cascade: the pulmonary gas exchanger, heart and blood, microvasculature, and mitochondria. The variations observed in these parameters are analyzed with respect to those in energy demand and are discussed in relation to the hypothesis of symmorphosis. We conclude that the design of the internal steps of the respiratory system (mitochondria, capillaries, blood, and heart) is matched to functional demand, whereas the lung maintains a variable excess of morphometric diffusing capacity which may be related to the facts that the lung has limited malleability and that it forms the interface with the environment. PMID- 1604055 TI - Control of metabolic and ventilatory responses to cold in anesthetized cats. AB - Interactions between the control of thermogenesis and ventilation were studied during normoxia, hyperoxia, and ambient or CO hypoxia in adult anesthetized intact or carotid-denervated cats. Shivering, metabolic and ventilatory responses to cold stress were studied. In addition, the effects of transient pharmacological stimulation (NaCN) or inhibition (Dopamine) of arterial chemoreceptor activity were studied under different levels of oxygenation. In intact animals, cold exposure provoked increases in VO2 and ventilation which were directly proportional to the intensity of shivering. During ambient or CO hypoxia, VO2 was less than in normoxia for all values of shivering intensity, suggesting that a non-shivering thermogenesis component may also be inhibited by hypoxia. The decrease in VO2 was associated with a smaller decrease in ventilation in ambient than in CO hypoxia because of the presence of the chemoreflex drive during ambient hypoxia. Pharmacological changes in chemoreceptor activity induced transient and opposite changes in ventilation and shivering intensity, confirming their role in the control of thermogenesis. After carotid denervation, when the drug effects were inconsistent or absent, changes in levels of oxygenation were still followed by changes in shivering activity and associated changes in VO2 and ventilation. We conclude that control of thermogenesis and ventilation and their interaction may be mediated by chemoreceptors as well as by direct effects upon central, possibly diencephalic structures. PMID- 1604057 TI - Diffusion-perfusion inhomogeneity and alveolar-arterial O2 diffusion limitation: theory. AB - Unequal distribution of pulmonary O2 diffusing capacity (D) to pulmonary blood flow (Q) (D/Q heterogeneity) leads to decreased alveolar O2 exchange efficacy. It is shown on simple models that the effect increases with increasing amount of inequality and with increasing value of the equilibration index, D/(Q beta) (beta, increment in blood O2 content per partial pressure increment). This inhomogeneity effect, if not taken into account, leads to spurious increases of D in hypoxia and with elevated O2 uptake. PMID- 1604059 TI - Chemoreceptor control of the airways. AB - The peripheral chemoreceptors act reflexly not only on respiration, but also on many motor systems in the respiratory tract. They cause a reflex bronchoconstriction, although this may be modified or even reversed by secondary dilator reflexes such as that from pulmonary stretch receptors. They promote a reflex secretion of mucus from submucosal glands in the trachea, and possibly other parts of the airways. They cause systemic reflex vasoconstriction both in nose (with reduction in airflow resistance) and trachea, and probably in the bronchi. There is also a reflex pulmonary vasoconstriction, although the strength of this has not been determined. The larynx dilates during peripheral chemoreceptor stimulation, as does the oropharynx. All these changes affect airway calibre, most components increasing it but some having the opposite effect. In turn these airway responses will affect lung ventilation and blood-gas tensions. The whole respiratory tract seems to be an important target organ for reflexes from the peripheral chemoreceptors. PMID- 1604058 TI - Pulmonary hypoxic vasoconstriction: how strong? How fast? AB - We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state. PMID- 1604060 TI - Effects of the thromboxane A2 mimetic, U46,619, on pulmonary vagal afferents in the cat. AB - Release of thromboxane A2 (TxA2) or infusion of the TxA2 mimetic U46,619 in the cat elicits pulmonary hypertension and rapid shallow breathing (Shams et al., Respir. Physiol. 71: 169-183, 1988). The vagus nerve mediates the observed respiratory, but not the circulatory, effects (Shams and Scheid, J. Appl. Physiol. 68: 2042-2046, 1990). To identify the type of lung vagal afferent fibers involved in this respiratory response to TxA2, we have recorded the functional single-unit activity and its response to infusion of U46,619 in fine strands of the vagus nerve in the artificially ventilated cat and rabbit. The fibers were classified as originating from slowly adapting (SAR) or rapidly adapting (RAR) stretch receptors by their response to sustained pulmonary inflation (intrapulmonary pressure of 20-25 cmH2O) or as C-fibers, by their response to a bolus injection of phenylbiguanide. C-fibers responded variably to lung inflation. U46,619 infusion caused only a small increase in SAR or RAR activity along with increases in end-inspiratory tracheal airway pressure (Paw), but evoked a marked increase in the firing rate of C-fibers, independent of their response to lung inflation. This increase in C-fiber activity was unrelated to the increase in Paw, which accompanied the infusion of U46,619. Since these responses remained the same after indomethacin they appear to be due to a direct action of U46,619, and not to be mediated by prostanoids that might be released by U46,619. These data suggest that C-fibers are indeed involved in the respiratory effects of TxA2. Since the effects exerted on C-fibers by U46,619 were unrelated to increased Paw, TxA2 is likely to stimulate the nerve endings directly, rather than via smooth muscle contraction. On the other hand, the small stimulating effect of U46,619 on SAR and RAR may be mediated by bronchoconstriction. PMID- 1604061 TI - Water balance and lung fluids in rats at high altitude. AB - A disturbed water and electrolyte homeostasis is not generally held to be a primary mechanism in the pathogenesis of acute mountain sickness (AMS) and high altitude pulmonary edema (HAPE), but the association of oliguria and weight gain with AMS and HAPE has led to the hypothesis that water retention may be a facilitative mechanism, possibly caused by an effect of hypoxia to release antidiuretic hormone (ADH). To examine the problem, normal Long-Evans rats (N) and the strain with congenital diabetes insipidus (DI) were exposed to hypobaric hypoxia (0.5 atm) for 4 days, and fluid balance in the whole animals and in their lungs was studied. Both strains reduced water intake and were oliguric on acute exposure, but the N rats gained body weight and increased lung water, while the DI rats increased neither body weight nor lung water. Neither strain increased lung blood at high altitude. The oliguria in the DI rats could not have been due to a release of antidiuretic hormone, and was attributed to the diminished water intake in both strains. The protection against HAPE in the DI rats was probably due to their more severe dehydration that exists already in normoxia, and its further increase in hypoxia, compared with N rats. PMID- 1604062 TI - Nest ventilation explains gas composition in the nest-chamber of the European bee eater. AB - The European bee-eater Merops apiaster builds a nest in soil banks comprising a horizontal corridor (159 cm) leading to a 3.4 L nest chamber. An adult and six eggs and/or nestlings occupy this nest for 60 d. Incubation and development are asynchronous. In order to evaluate the gas exchange pattern of the occupied nest, we measured the O2 diffusive conductance of the nest with the ambient environment (GNO2), its internal O2 and CO2 pressures (PNO2 and PNCO2), temperature (TN) and observed the sequences of development and the frequency of parental visits. We also measured the rate of O2 uptake (MO2) of the eggs, nestlings and adults. The GNO2 was 10.9 ml[STPD]/(h.Torr). The PNO2 dropped and the PNCO2 increased during incubation and growth to a maximal change of 24 and 23 Torr, respectively. Maximal MO2 of an egg and a nestling were 5.4 and 146 ml[STPD]/h, respectively. The MO2 of an adult at rest and at TN (27 degrees C) was 90.5 ml[STPD]/h. From clutch size, sequence of nest events, and the above values we have estimated a maximal nest chamber ventilation (VN) of 0.8 L/min necessary to prevent lowering PNO2 to 74 Torr below ambient PO2. This convection is achieved chiefly by the parental feeding visits (up to 40/h). Thus, movement along the corridor convects 1.2 L per visit. PMID- 1604063 TI - Acid-base changes on transfer between sea- and freshwater in the Chinese crab, Eriocheir sinensis. AB - The time course of changes in hemolymph pH, PCO2 and bicarbonate concentration were followed in euryhaline Chinese crabs, Eriocheir sinensis, after transfer from seawater (SW) to freshwater (FW) and vice versa. In order to correlate these changes with the animal's ionic status, hemolymph osmolarity and Na+ and Cl- concentrations as well as net exchanges of acid-base equivalents with the external water were also measured. Transfer from SW to FW induced a metabolic alkalosis which peaked after 3 days and declined thereafter but remained significant by 29 days. Hemolymph PCO2 was markedly elevated in FW, thus moderating the increase in hemolymph pH. Osmolarity and Na+ and Cl- concentrations reached a new steady state at lowered values by 24-48 h and a significant outflux of acidic equivalents was measured only during the first 2 days. Transfer from FW to SW conversely induced a metabolic acidosis which was almost fully compensated by a marked hypocapnia. It is concluded that external acid-base exchanges coupled to ionic readjustments following a salinity transition cannot solely explain the associated acid-base disturbances, the metabolic component of which must also rely on tissular processes probably linked to cell volume regulation. PMID- 1604064 TI - Seawater salinity and blood acid-base balance in the lugworm, Arenicola marina (L.). AB - The kinetics of variations in the blood acid base balance (ABB) were investigated in a moderately euryhaline osmoconformer, the lugworm Arenicola marina (L.), exposed to natural and experimental hypo- or hyperosmotic shocks. In natural as well as in experimental conditions, a hyposmotic shock induced a transient and essentially metabolic acidosis, probably linked to the ionic readjustments following the shock, which was rapidly overridden by a metabolic alkalosis. In field conditions, a new ABB equilibrium was then attained, the metabolic alkalosis being neutralized by the respiratory and metabolic acidosis occurring normally in the lugworm during low tide. Conversely, in the normoxic conditions of our laboratory experiments, a new ABB equilibrium was never reached. Under experimental conditions, a hyperosmotic shock always induced a respiratory and metabolic acidosis. In the field, this phenomenon must occur at the beginning of high tide and must help to restore normal blood ABB in lugworms submitted to a moderate hyposmotic shock during low tide. All the observed blood ABB variations reveal the complex intracellular processes through which the lugworm submitted to moderate osmotic shocks tentatively regulates, sometimes without any real success, its osmoticity and volume. Obviously, complementary physical, physiological and behavioral mechanisms allow the lugworm to live in sediments washed by almost fresh water during a 7-8 h 'low tide'. PMID- 1604065 TI - Planned versus attained design in phase II clinical trials. AB - The standard phase II trial problem is to decide whether or not to continue the testing of a new agent (or combination). Typically, one tests the null hypothesis HO: p = pO against the alternative HA: p = pA, where p is the probability of response. There is available a variety of two-stage phase II designs, including optimal designs according to various criteria. Practical considerations in the conduct of multicentre trials, however, make it difficult to follow designs precisely. We investigate several approaches to adapting stopping rules when the attained sample size is not the planned size. We find that a simple approach of testing HA: p = pA at the 0.02 level at the first stage and HO: p = pO at the 0.055 level at the second stage works well across a variety of powers, pOs and pAs. PMID- 1604066 TI - k-ratio t tests for multiple comparisons involving several treatments and a control. AB - We consider the problem of simultaneously comparing several treatment means with a control mean and also with one another. Following an elementary decision theoretic Bayesian approach requiring the choice of a type-I to type-II error seriousness ratio k, a posteriori t tests are derived for testing both treatment versus control (TvC) and treatment versus treatment (TvT) differences. These k ratio t tests are strictly comparisonwise in nature. That is, the test applied to any TvC or TvT difference d, depends in no way at all on whether the other differences are being tested. The test for d, however, does depend on the sizes of the other differences through tG, the standardized average of the observed TvC differences, and through FT, the observed between-treatments F ratio. From these adaptive dependences on tG and FT, the critical t values can be large or small, thus avoiding the intuitive objections of under- or over-conservatism in classical comparisonwise or experimentwise level testing rules. PMID- 1604067 TI - A comment on replication, p-values and evidence. AB - It is conventionally thought that a small p-value confers high credibility on the observed alternative hypothesis, and that a repetition of the same experiment will have a high probability of resulting again in statistical significance. It is shown that if the observed difference is the true one, the probability of repeating a statistically significant result, the 'replication probability', is substantially lower than expected. The reason for this is a mistake that generates other seeming paradoxes: the interpretation of the post-trial p-value in the same way as the pre-trial alpha error. The replication probability can be used as a frequentist counterpart of Bayesian and likelihood methods to show that p-values overstate the evidence against the null hypothesis. PMID- 1604068 TI - Estimation of direct formulation effect under log-normal distribution in bioavailability/bioequivalence studies. AB - This paper considers estimation of a measure of relative bioavailability of a test formulation to a reference formulation, on the original scale, under the assumption of a log-normal distribution for the data from a 2 x 2 crossover bioavailability/bioequivalence study. We propose the minimum variance unbiased estimator which is equal to the maximum likelihood estimator adjusted for bias by a correction factor. We also derive the variance of the minimum variance unbiased estimator and its unbiased estimator. We derive the biases and mean square errors of the maximum likelihood estimator, the ratio of the least square means, and the least squares mean of individual subject ratios, with respect to this measure, and compare them in a simulation study. Both theoretical and empirical results strongly suggest that one always consider the minimum variance unbiased estimator. A numerical example illustrates the proposed estimation procedure. PMID- 1604069 TI - Estimation, reference ranges and goodness of fit for the three-parameter log normal distribution. AB - The three-parameter log-normal distribution (3PL) is an appropriate model for many of the continuous variables encountered in medicine. It is shown how to obtain different types of estimate and approximate (sometimes conservative) confidence intervals for the parameters of the 3PL and for certain functions of them, particularly in the calculation of reference ranges of clinical measurements. A simple non-iterative estimate of the shift parameter is described. The Shapiro-Wilk test of non-normality is modified to allow it to be used for testing for departure from the 3PL. Its power is compared with that of other well-known tests. The methods are illustrated using several data sets. PMID- 1604070 TI - Exact unconditional tables for significance testing in the 2 x 2 multinomial trial. AB - This paper presents tables analogous to T-tables for use in the 2 x 2 multinomial trial, where the continuity corrected Z-statistic is used to make exact unconditional inference. This is the first solution of a discrete exact unconditional inference problem involving a multivariate nuisance parameter for which no ancillary statistic exists. PMID- 1604071 TI - On the computation of likelihood ratio and score test based confidence intervals in generalized linear models. AB - Numerical procedures for calculating likelihood ratio test and score test based confidence intervals in generalized linear models are considered. Newton's method appears to have better convergence properties than the secant method in the likelihood ratio test case. However, the secant method may be easier to program for models with link functions that are not natural. Similarly, the secant method is easier to implement for the computation of score test based intervals. The practical implementation of the procedures in GLIM is illustrated. PMID- 1604072 TI - Parametric versus non-parametric methods for estimating cure rates based on censored survival data. AB - If a patient's failure time is incorrectly recorded as being too early, the correction will lower the plateau of the Kaplan-Meier curve and, hence, the associated estimated cure rate. Implications of this counter-intuitive observation are discussed. In addition, a parametric approach, based on the Gompertz distribution, to the problem of cure rate estimation is presented. PMID- 1604073 TI - Bias in relative odds estimation owing to imprecise measurement of correlated exposures. AB - A series of graphs is presented that show the estimated degree of bias in logistic coefficient estimates for two correlated continuous exposures measured with imprecision. These graphs indicate that even when the correlation coefficient between the exposure of interest and a correlated exposure is as low as 0.2, imprecision in the measurement of the latter exposure can result in at least as serious bias in the logistic coefficient estimate for the exposure of interest as measurement imprecision in the exposure of interest itself. The implications for the design and interpretation of epidemiological studies are discussed. PMID- 1604075 TI - [Severe hyperthyroidism induced by iodine: a medicosurgical emergency]. PMID- 1604074 TI - [Hormonal contraception]. PMID- 1604076 TI - [Psychiatric emergencies: a thorny daily problem]. PMID- 1604077 TI - [What is your diagnosis? Ruptured Baker's cyst]. PMID- 1604078 TI - [The clinical diagnosis of heart failure]. AB - Clinical diagnosis is easily established at bedside or in the doctor's cabinet. Four clinical symptoms have to be considered: 1) functional impairment of the left ventricle, 2) intolerance to physical stress, 3) congestion and 4) ventricular arrhythmia (not covered in this paper). History provides the keys for 1, 2 and 3, physical examination for 1 and 3, electrocardiography under exercise for 2 and chest X-ray for 3. PMID- 1604079 TI - [What does echocardiography contribute to heart failure?]. AB - When examining patients with heart failure, it is often impossible to assess the underlying cardiac disease only on the basis of clinical examination, electrocardiogram and chest X-ray. As an additional noninvasive method, echocardiography provides a high level of diagnostic accuracy for heart diseases. Different cardiologic ultrasound methods and procedures, applied in patients with heart failure during a modern echocardiographic routine examination, are shown. Despite an increasing availability of this imaging technology, inappropriate use without clear indication must be avoided. Criteria of indication are discussed, followed by an illustrating case report. PMID- 1604080 TI - [Therapy of chronic heart failure]. AB - Symptoms of chronic cardiac failure depend on four determinants: The initial event concerns a decrease in contractility. The resulting complex neurohumoral regulatory mechanisms are essentially sympathicomimetic and stimulate the renin angiotensin system. Accordingly, pre- and afterload will increase and symptoms may become aggravated by dys- or arrhythmias. Symptomatic pharmacotherapy of cardiac failure is directed to these four determinants. The actual rationale for its use is presented, putting emphasis on the renewed controversy on digitalis and on the importance of vasodilators, in particular ACE inhibitors. The relevance of diagnostic evaluation before and during treatment is indicated. The adaptation of treatment according to different causative disorders leading to cardiac failure is outlined. Finally, open questions and unsolved problems are brought up. PMID- 1604081 TI - [What is your diagnosis? Hairspray sniffer]. PMID- 1604082 TI - [Modern nuclear medicine--indications for general practice]. AB - For the general practitioner scintigraphic investigation of the skeleton and the lung and the isotope techniques for evaluation of diseases of the thyroid are important. Scintigraphy of the skeleton and the lung, the latter consisting of ventilation and perfusion tests, are briefly described. Examples are used to outline the most important indications for these studies. Investigations of the thyroid comprises basic procedures such as chemical tests, sonography, scintigraphy, eventually complemented by fine-needle aspiration, as well as treatments with radioactive iodine isotopes. Finally, the recently introduced densitometry of bones is briefly discussed. PMID- 1604083 TI - [Clarification of a political assassination in 1839: statesman Johannes Hegetschweiler shot during civil unrest in Zurich]. AB - The death by violence of the scientist and statesman Johannes Hegetschweiler (1789-1839), M.D., constituted a double tragedy: just previously, at the instigation of his friends, he had withdrawn an already submitted petition to be relieved of all his public functions. And from the outset he declared himself an opponent to the appointment of the theologian Friedrich David Strauss to the Zurich Professorship for Dogmatics, an appointment leading to political unrest ('Zuriputsch'). On September 6, 1839, Hegetschweiler dashed, as a member of the Cantonal Government, between the militia of the Government and the advancing insurrectionists with instructions to effect a cease-fire. While doing so, he was wounded in the head by a deliberately aimed discharge of a shot, succumbing after three days of suffering. The general turbulence occasioned by the Zuriputsch, the unprecedented animosity among the political misdemeanors and felonies rendered any legal prosecution impossible. It is here proven that one of the insurrectionists from the Zurich Oberland is the only person who can be considered as the murderer of Hegetschweiler. PMID- 1604084 TI - [Complex disorders of radius and ulna in childhood]. AB - Treatment of congenital or acquired disturbances of the radius or ulna always requires recognition of the complex biomechanics of the forearm. In particular trauma, seemingly restricted to one of the bones, should caution against concomitant lesions to the other bone. The typical example is unfortunately the often missed dislocation of the capitulum radii in Monteggia-type lesions. Additional examples are deranged growth of the distal epiphysis of the radius after a fracture of the ulna, in association with multiple osteochondromas and of the proximal epiphysis of the radius in presumptively congenital dislocation of the capitum radii. Lesions encountered in children have to be analyzed carefully with respect to dynamics of maldevelopment. Corrections that have implications for neighbouring articulations should be undertaken with the intent to fully exploit the potential for remodelling by forthcoming growth processes. PMID- 1604085 TI - [Fibrocystic changes of an upper lung lobe--an unusual late complication in ankylosing spondylitis]. AB - Alterations of pulmonary parenchyma are complications of ankylosing spondylitis. A 60-year-old man presented with extended fibrocystic changes in the right upper pulmonary lobe in the course of ankylosing spondylitis of many years duration. Pneumonia refractory to treatment and hemoptysis developed as complications necessitating pneumonectomy. PMID- 1604087 TI - [What is your diagnosis? Urticaria in acute hepatitis B]. PMID- 1604086 TI - [A case from practice (244). Polyradiculitis, Guillain-Barre type, in the framework of an HIV-infection]. PMID- 1604088 TI - [Possibilities and limitations of surgical therapy in acute and chronic heart failure]. AB - Five out of the many scenarios for surgical interventions in manifest or imminent heart failure that are of special importance for the practitioner as well as the attending physician are covered. In the context of acute heart failure, mechanical complications of infarction and acute aortic insufficiency in the course of infectious endocarditis are discussed. In a second part, heart failure in chronic regurgitation of the aortic valve and chronic ischemic heart disease are treated. Main attention is given to medical indication for surgical intervention. PMID- 1604089 TI - [Rational assessment procedure in hypertension]. AB - Diagnosis of hypertension is based on a classification of blood-pressure values, determined by multiple blood-pressure measurements over a period of several weeks or months. However, possibility of a so-called 'white coat effect' has to be considered, i.e. a marked increase of blood-pressure values in the presence of medical persons. Multiple control-measurements by the patient himself or an ambulatory day profile may clarify the situation in suspicious cases. In the case of pure 'white coat' hypertension, no further investigation is necessary, since cardiovascular complications only correlate with the 'usual' ambulatory blood pressure. Persons with borderline (141-159/91-94 mmHg and intermittently lower, according to the WHO) or established hypertension usually present with further cardiovascular risk factors, like lack of physical exercise, smoking, hypercholesterolemia (elevated total cholesterol/HDL-cholesterol), alone or accompanied by hypertriglyceridemia, disturbed tolerance of glucose or diabetes mellitus, or hypertrophy of the left ventricle. Therefore, in borderline as well as in established hypertension these additional risk factors have to be evaluated. Considering left ventricular hypertrophy electrocardiogram and chest X ray are insensitive with regard to diagnosis and prognosis of this important and serious risk factor. Echocardiography that can meet both these criteria is for capacity reasons still limited to selected cases. In contrast to the investigation of the risk profile, only few patients will profit from an investigation of etiology of hypertension. It should be tailored to individual features and after thorough evaluation of all consequences, such as costs for the patient, chances for a positive result and possible therapeutical consequences. Usually, careful history taking, clinical investigation and routine laboratory provide an appropriate basis for further rational investigative procedures. Hypertension is a common and important risk factor. The challenge for the public health is great because prognosis can markedly be influenced by early diagnosis and therapy. Insufficient distinction between efficient diagnostic and therapeutical efforts and those that may be superfluous may not only influence psyche and somatic well-being of the patient but also socio-economic balance. PMID- 1604090 TI - [Ambulatory long-term blood pressure determination: technique and ways of risk identification]. AB - Traditional noninvasive measurement of blood pressure with the sphygmomanometer has as a punctual method been considerably expanded by the development of methods for recording blood pressure repeatedly under normal daily activity. Such procedures have contributed much to understanding of circadian regulation of blood pressure. Normo- and hypertensive patients experience a physiologic drop in systolic and diastolic blood pressure during night hours. Ambulatory blood pressure recordings are suitable to increase treatment compliance by patients. They allow qualitative evaluation of antihypertensive treatments and elimination of overshooting reactions to the measuring process by the physician (white-coat effect). This method has the potential for better definition of cardiovascular risk factors through recording of circulatory stress by blood pressure. No accepted guidelines exist, however, to date for definition of normal values for such measurements. The upper limits of normality for averaged blood pressure appear to be 140/90 mmHg during the day and 120/80 mmHg at night. PMID- 1604091 TI - [Acceptance of 24-hour blood pressure determination]. AB - In interviews with 247 patients acceptance and behaviour during 24-hour ambulatory blood-pressure recording were studied. In contrast to previous assumptions it was shown that the blood-pressure profile was not recorded during normal activities for a great part of patients. Very often the patients reduced their activity over the day. Our results show that for wider distribution and applications of this procedure the measuring devices have to be improved. A substantial part of patients experienced the ambulatory blood-pressure recording as an comfortable, such that one of eight patients declined a further recording and 20% of the patients complained about disturbed sleep. PMID- 1604092 TI - [A case from practice (245). Acute altitude sickness with suspicion of altitude induced pulmonary edema]. PMID- 1604093 TI - [What is your diagnosis? Butterfly glioma originating from the corpus callosum]. PMID- 1604094 TI - [Hepatitis A to E: current diagnosis]. AB - Diagnosis of viral hepatitis is based on epidemiologic data (information about travels, blood transfusions, contacts with persons suffering from hepatitis, etc.) and on results of physical examination and laboratory investigations. Usually, serologic and genomic analysis lead to the specific proof of the viral etiology: HAV, HBV/HDV, HCV and HEV. If these infections are not detected, nonviral causes of hepatopathy should be investigated (i.e. toxic, pharmaco toxic, metabolic, immunologic, etc.). PMID- 1604095 TI - [Hepatitis A to E: symptoms, clinical aspects, prognosis]. AB - Symptoms of acute viral hepatitis during the prodromal period are non-diagnostic. Icteric periods are rare in acute hepatitis C, but frequent in patients with hepatitis A and E. Clinically, the liver is palpable in 70 to 90%, whereas the spleen is rarely augmented (5 to 10%). The various forms of acute hepatitis can not be distinguished clinically. The prognosis depends on the type of the virus (mutant?) and the immune reaction of the organism. Cases of chronic hepatitis are unknown following acute hepatitis A and E. However, 40 to 70% of patients with sporadic or posttransfusion hepatitis C develop chronic hepatitis. The chronicity rate of acute hepatitis B depends markedly on the age of patient at the time of infection. About 3 to 5% of the patients develop chronic hepatitis when infected in adult life. The chronicity rates increase markedly if patients are infected with the delta-virus (HDV-superinfection). A fulminant course of hepatitis A and E is a very rare event, except in the case of pregnancy in acute hepatitis E. Infection with HBV-mutants and HCV-infection both are associated with a higher frequency of fulminant courses. Patients with presumed fulminant hepatic failure due to sporadic HCV-infection contribute significantly to the numbers of cases of fulminant hepatitis. PMID- 1604096 TI - [Immunological diagnosis in non-viral liver diseases]. AB - The demonstration of defined autoantibody specificities in autoimmune liver diseases allows the differentiation between chronic inflammatory processes affecting mainly the parenchyma (autoimmune chronic active hepatitis) or the bile ducts (primary biliary cirrhosis, primary sclerosing cholangitis). Furthermore, overlap syndromes between the different autoimmune liver diseases as well as with other disorders including collagen disorders can be observed. The determination of antibody-profiles--especially in PBC--is helpful to evaluate the prognosis of the disease even in early stages. PMID- 1604097 TI - [Therapy of alcoholic hepatitis]. AB - The basic therapeutic principle in alcoholic liver diseases in general and in alcoholic hepatitis in particular is the consequent withdrawal of alcohol intake. Basic therapy of more complicated causes includes well balanced nutrition and symptomatic treatment according to the known principles of hepatology and intensive care medicine. Infusions with glucose-glucagon-insulin, or the administration of silymarin, and in individual cases of glucocorticoids seems to be justified as additional treatment. The therapy with S-adenosyl-L-methionine is promising, but clear evidence of the therapeutic effect has to be supplied by clinical studies. Liver transplantation should be taken into consideration in prognostically infaust cases. PMID- 1604098 TI - [Acute liver failure: current hepatological-surgical therapy results]. AB - For fulminant hepatic failure the prognosis is depending on the onset of severe encephalopathy (coma grade III to IV), cerebral oedema, renal and respiratory failure. Treatment strategies must be devoted to limit these complications and proceed with an urgent liver transplantation. Overall 1-year survival rates after hepatic transplantation in fulminant liver failure are as high as 80%. PMID- 1604099 TI - [Definition and classification of vascular acro-syndromes]. PMID- 1604100 TI - [Raynaud's phenomenon and systemic diseases: immunological viewpoint]. PMID- 1604101 TI - [Peri-ungual capillaroscopy]. PMID- 1604102 TI - [Hematological aspects of acro-syndromes]. PMID- 1604103 TI - [Treatment of acro-syndromes]. PMID- 1604104 TI - [Febrile status in a chronic alcoholic]. PMID- 1604105 TI - [Cancer of the eye in children: a reality and a challenge]. PMID- 1604106 TI - [Pulmonary transplantation]. PMID- 1604107 TI - [Problems in bioethics. How to sensitize the young generation to bioethical problems--a task of actively approaching on various levels of education]. PMID- 1604108 TI - [General medicine and prevention: utilization of computers]. PMID- 1604109 TI - [Neuronal cytoskeleton: structural, functional and dynamic aspects]. AB - The cytoskeleton of practically every type of cell is constituted by 3 types of filaments: microfilaments, microtubules and intermediate filaments. The latter are cell-type specific and are represented in neurons by neurofilaments accompanied by other intermediate filaments, which have recently been described and whose nature depends on the period of development and on the neuronal type. Numerous studies demonstrate that many proteins are associated with microfilaments and microtubules and that they are responsible not only for the structure of the lattices but also for their function and dynamics. Moreover, these proteins can link one type of filament to another, and the network thus constituted, to the plasmic membrane and probably also to the nuclear membrane. The neuronal cytoskeleton is not static; it has, of course, a very important role in the maintenance of the structural integrity of the neuron, but it is also the promoter of axonal growth, the substratum against which many organelles move and thus has an essential role in axonal transport. In a few neuropathies chosen as examples for a disturbed axonal transport, abnormal bundles of filaments are observed; they are probably the end product of a primary disorder which has still to be analyzed. PMID- 1604110 TI - [Idiopathic cranial polyneuropathies]. AB - A series of 43 cases with multiple cranial nerve deficits was collected between 1972 and 1990. No diagnosis was established in 15 cases. The facial and the trigeminal nerves were most frequently affected. In 10 cases, a monophasic course was observed usually with recovery. Recurrence was present in 5 cases. An inflammatory mechanism was likely in 10 cases. Nosological relations between these cases and either Bell's palsy (idiopathic facial paralysis) or Tolosa Hunt's syndrome are discussed. PMID- 1604111 TI - [Neurobiochemistry of experimental lesions of the basal nucleus of Meynert]. AB - Lesions of the nucleus basalis magnocellularis (of Meynert) in rats induce severe cognitive impairments, in both mnesic and attentional functions. During the last 10 years, many studies tended to establish some relationships between the behavioral and biochemical effects of such lesions. Recent data show that the activity of some peptidergic and glutamaterigic neurons in target areas is modified by cholinergic deafferentation. A new physiological interpretation may be proposed for the associated cognitive deficits. PMID- 1604112 TI - [Familial parkinsonian syndrome with athymhormia and hypoventilation]. AB - Five cases of parkinsonism with athymhormia observed in a single family are reported. Death caused by central respiratory disorders occurred after 6 to 8 years of progressive course. In 2 cases with autopsy, there was a severe neuronal loss predominant in the substantia nigra. Other brain stem nuclei (locus coeruleus, dorsal motor nucleus of the vagus nerve, nucleus of the tractus solitarius) were involved, as well as the striatum, pallidum and frontal cortex. No Lewy body was seen. In the surviving patient, positron emission tomography demonstrated, 4 years after the onset, a bilateral frontal hypometabolism. This disease is a rare variety of familial parkinsonism of dominant inheritance, already reported in 2 Canadian families by Perry et al. (1975) and Purdy et al. (1978) and in a family of West Virginia by Roy et al. (1988). The respiratory disorders can be explained by the involvement of the dorsal medullary nuclei. The peculiar neuropsychological disorder and motor slowing are best accounted for by the functional impairment of both motor and limbic striato-pallido-thalamo frontal loops. PMID- 1604113 TI - [Typical and atypical forms of neuralgic amyotrophy of the shoulder: 86 cases]. AB - Eighty-six cases of neuralgic shoulder amyotrophy are reported. Among these, 67 cases were concordant with the usual semeiological description. The other cases were atypical in their anatomical distribution (extensive or restricted to peripheral nerve rami), in their course (chronic or recurrent or alternating from one side to the other) and in their cause, notably familial forms. The continuum existing between these variants is most probably due to an immuno-allergic mechanism. PMID- 1604114 TI - [Myelitis caused by toxocara canis (larva migrans)]. AB - A young woman presented with recurrent myelitis associated with persistent eosinophilia in blood and CSF. Specific serological procedures in blood and CSF led to the diagnosis of visceral larva migrans. The patient recovered after 21 days of treatment with diethylcarbamazine. To our knowledge, this is the second report of myelitis in the course of visceral larva migrans. PMID- 1604115 TI - [Malignant degeneration of epidermal cyst of the posterior cranial fossa. Diagnostic value of magnetic resonance imaging]. AB - A 72 year-old woman presented with a rapidly evolving left cerebellopontine angle syndrome secondary to a squamous cell carcinoma developed in an epidermoid cyst. The value and the results of magnetic resonance imaging are discussed. PMID- 1604116 TI - [Selective sensitivity of cysts to praziquantel and albendazole in a case of cerebral cysticercosis]. AB - A case of neurocysticercosis in a Zairian patient with clinical and neuro radiological follow-up is reported. Treatment with praziquantel resulted in the regression of only some of the cysts. Subsequent treatment with albendazole was effective, eliminating most of the remaining lesions. This case illustrates a selective sensitivity of cysts to praziquantel and albendazole in a single patient. PMID- 1604117 TI - [Facial paralysis and chicken-pox]. AB - Ten days after chicken-pox, a 24-year old man presented with a right facial palsy without meningitis. Albumino-cytologic dissociation in CSF--not observed in two other published cases--suggests an immune-mediated process. The patient was treated by prednisone and aciclovir. The upper facial muscles remained paretic 2 months after onset. PMID- 1604118 TI - [Conference at Salpetriere Hospital. January 1990. Progressive motor incoordination in a man with late partial epilepsy]. PMID- 1604119 TI - [Multiple sclerosis and suicide]. PMID- 1604120 TI - [Total deafness after multiple pontine infarctions. Dolichoectasia of the basilar trunk]. PMID- 1604121 TI - [Neuropsychological evaluation before and after thalamic stimulation in 9 patients with Parkinson disease]. AB - Chronic thalamic-VIM stimulation was performed in 9 parkinsonian patients with disabling tremor and poor response to drugs. Neuropsychological assessment was performed before and after deep brain electrode implantation and stimulation. Mild cognitive disorders were observed prior to thalamic implantation. Neuropsychological testing failed to show intellectual function worsening after implantation and stimulation. We conclude that thalamic stimulation could be an appropriate treatment of untractable tremor as this could provide less neuropsychological side-effects than thalamotomy, especially in Parkinson's disease. PMID- 1604122 TI - [Diffuse cerebral gliomatosis. An anatomoclinical case]. AB - A 52-year old man had a generalized seizure followed by progressive memory disturbances, affective changes, right hemiplegia and aphasia. He died 4 years later after a period of coma. Neuropathological findings included slight cortical atrophy, pallor of the centrum ovale, and infiltration of the cortex and subcortical white matter by neoplastic glial cells, with neither major neuronal loss nor spongiosis. Microglial rod cells were observed. The gliomatosis extended within the thalamus and subthalamic area on both sides, whereas the brain stem was much less involved. The spinal cord and peripheral nerves were not examined. Abnormal glial cells were stained by the glial fibrillary acid protein, which confirms the astrocytic differentiation of the tumoral cells. PMID- 1604123 TI - [Bilateral deafness, an initial manifestation of meningeal carcinomatosis]. AB - Three cases of bilateral deafness with cytologically-demonstrated meningeal carcinomatosis are reported. The first patient, a 64-year old man, presented with bilateral deafness, gait disturbances, and bilateral facial paresis. The second patient, a 78-year-old man, had bilateral deafness, unsteady gait and fluctuations in consciousness. The last patient, a 69-year-old man, complained of bilateral deafness and severe headache, and presented with right facial paresis and left laterodeviation while walking. All three patients had abnormal cochleo vestibular findings and brainstem auditory evoked responses (BAER) that suggested peripheral lesions with absent or very delayed I waves. The brain CT scans with an without contrast enhancement were entirely normal, and the diagnosis was established by lumbar puncture. From our own cases and a review of the literature, deafness in meningeal carcinomatosis may start unilaterally but becomes bilateral in less than a week. Vestibular disturbances may not be apparent, but they can be demonstrated in almost all cases. Facial paresis or plegia is also a very frequent finding. The destruction of the eighth and seventh cranial nerves is probably due to direct infiltration by neoplastic cells as well as to ischemia through compression of the nerve supplying vessels. The 3 cases presented here emphasize once again the important fact that meningeal carcinomatosis remains a cytological diagnosis, several lumbar punctures being sometimes necessary, and that cerebrospinal fluid studies cannot yet be supplanted by other diagnostic techniques like contrast-enhanced CT or MRI with gadolinium. PMID- 1604124 TI - [Cerebral phlebitis and Crohn disease]. AB - A 17 year-old man with a one-year history of Crohn's disease presented with superior sagittal sinus thrombosis in spite of an apparent remission of the inflammatory bowel disease. Under treatment, the neurological disorders rapidly improved. Hematological studies showed mild thrombocytosis, spontaneous platelet aggregation, and an increase of the fibrinogen level, plasmatic viscosity and red blood cells aggregability. Mild hypofibrinolysis and antiphospholipid antibodies were also noted. Nine fully documented cases of cerebral venous thrombosis associated with an inflammatory bowel disease are reviewed. The possible prothrombotic role of thrombocytosis and other hematological disorders is discussed. PMID- 1604125 TI - [Juvenile arteriosclerotic leukoencephalopathy: anatomoclinical study of a case]. AB - A 34-year old right-handed man was suffering from recurrent cerebro-vascular insults. CT-scans revealed several subcortical lacunar infarcts, and leukoaraiosis. Arteriography of the left and the right carotid arteries was performed respectively on the 4th and the 9th year of the disease, and did not elicit significant extracranial and intracranial vascular lesions. There were no arguments in favor of infectious, inflammatory, or auto-immune vascular diseases. The patient had tardive hypertension and dementia, and died at the age of 44. Pathological findings, limited to the brain and cervical spinal cord, revealed numerous ischemic lacunar infarcts. Histological lesions were consistent with the diagnosis of arteriosclerotic leukoencephalopathy. There were oedema, palor, and loss of myelin in the white matter, and nonspecific diffuse arteriosclerotic lesions that were particularly pronounced in the intimal part of the arterial wall. No inflammatory process nor amyloid deposits were found. Despite the onset of the disease in a young adult and the late occurrence of hypertension, our case report shares most of the pathological features of the Binswanger's type of arteriosclerotic encephalopathy. PMID- 1604126 TI - [Arachnoid cyst of the temporal fossa. Subdural hematoma. Contribution of MRI]. AB - A 20-year old man presented with an arachnoid cyst of the middle fossa and a subdural hematoma (SDH). An intra-cystic hemorrhage masked the presence of the SDH on CT. MRI demonstrated a communication between cyst and SDH. The mechanism of SDH formation is discussed. PMID- 1604127 TI - [Cavernous angioma of the cervical spinal cord]. AB - A 34-year old man gradually developed a paraparesis which spontaneously regressed within a few months. One year later, the patient suffered from acute torticollis immediately followed by flaccid tetraparesis with pyramidal signs, dissociated sensory deficit and acute retention of urine. Magnetic resonance imaging (MRI) showed, in the cervical cord, a vascular malformation that was not opacified at angiography. The lesion, a cavernous angioma, was surgically removed, leading to recovery. So far, thirty five cases of spinal cord angioma have been published, most of them since the advent of MRI which makes it possible to determine the exact incidence of this lesion, as well as its signs, symptoms and course. PMID- 1604128 TI - [Conference in Salpetriere Hospital. March 1990. Otalgia and hemicrania with rapidly progressive contralateral hemiparesis]. PMID- 1604129 TI - [Genetic counseling in neurology]. AB - Recent advances in biological techniques have resulted in an ever increasing number of neurogenetic diseases being characterized at molecular level or mapped by polymorphic markers which provide the diagnosis. Thus, side by side with the management of the patients, a genetic management extended to the family is progressively taking shape. This familial care is not without technical and ethical problems. PMID- 1604130 TI - [Intracranial cavernous angioma]. AB - Cavernous angiomas are vascular malformations that belong to the group of hamartomas. Evidence to support the hypothesis that some intracranial cavernous angiomas are benign vascular tumors is lacking. As they are angiographically occult, cavernous angiomas were largely overlooked and were considered rare before CT scan and MRI became available. Both of these techniques provide a quick and accurate diagnosis in cases of epilepsy, brain hemorrhage or intracranial hypertension. Most of the hemispheric cavernous angiomas are situated subcortically, in the neighborhood of the rolandic fissure. In the brain stem, they can be found mostly in the pons. Cerebellum and spinal cord are seldom involved. Cavernous angiomas may occur in children, as well as in familial forms, or in association with other visceral locations. It is important to know that some cavernous angiomas are able to grow, owing to a variety of mechanisms, which may result in rupture and cerebral hemorrhage. The improvement of both imaging and surgical techniques have reduced the risks of death or heavy sequelae. Some deeply located cavernous angiomas, however, are still inaccessible to surgery. PMID- 1604131 TI - [Spasmodic dysphonia. Investigation and therapeutic methods]. AB - We report the successful treatment of three patients with adduction spasmodic dysphonia by direct injection of botulinum toxin into the vocal cord(s). This was achieved under electromyographic control, and this and other otolaryngeal techniques were used to monitor treatment and study this often puzzling condition. PMID- 1604132 TI - [Memory and language disorders in Alzheimer's dementia]. AB - Memory dysfunction is the most notable feature of dementia of the Alzheimer type and is virtually mandatory for this diagnosis. The disruption of language ability is also a prominent clinical feature of this disease. Recent advances in cognitive neuropsychology suggest that Alzheimer type dementia in the early stages of the disease can be characterized by abnormalities but also by sparing of other cognitive mechanisms, particularly in memory and language. Nevertheless, many studies indicate an heterogeneity in cognitive profiles. This existence of subgroups of patients with Alzheimer type dementia would have important implications for therapeutic studies as well as investigations concerned with etiology. PMID- 1604133 TI - [Mixed pre- and postsynaptic neuromuscular block]. AB - We report a new case of neuromuscular block overlap between Myasthenia Gravis and Eaton-Lambert syndrome. A 64-year-old man with a 4-months history of gait disturbance was admitted for ophthalmoplegia worsening during exercise and decreasing at rest. Clinical examination after exercise, revealed limbs weakness and areflexia, palsy of the left eye abduction and a left ptosis. The level of anti-acetylcholin-receptor antibodies was high. Electrophysiological explorations revealed a decrement at 3 Hz and a increment at 30 Hz, with a reduction in amplitude of the initial motor potential. This patient improved under a combination of guanidine and anticholinesterase drugs. From this case and 9 previously reported cases, we propose 4 criteria for the diagnosis of such neuromuscular blocks: 1) exercising symptoms and signs, including areflexia, 2) presence of anti-acetylcholin-receptor antibodies, 3) reduction of the amplitude of the initial motor potential, with a decrement at 3 Hz, and an increment at 30 Hz, and 4) clinical and electrophysiological improvement under guanidine and anticholinesterasic drugs therapy. PMID- 1604134 TI - [Non hypertrophic amyloid myopathy with muscular inflammation in plasma cell dyscrasia]. AB - The case of a 41 year old woman with amyloid myopathy is reported. Clinical involvement consisted of limb girdle muscle weakness, mild scapular muscle atrophy and dysphagia. In contrast with the published cases, abnormal firmness, pseudohypertrophy of the musculature and macroglossia were absent. Muscle biopsy showed endo- and perimysial amyloid deposits but also inflammatory infiltrates. Inflammatory cells typing was studied by immunocytochemical methods and revealed a predominant T-helper cell infiltration. Free kappa light chains were present in serum and urine. Serum immunoglobulin levels were reduced. Bone marrow examination revealed mild plasmocytosis without abnormal cells. Immunofluorescence and immunoperoxidase techniques for identification of the type of amyloid fibrils showed positivity with antisera to kappa light chains. A 4 year follow-up revealed a progressive worsening of muscle weakness despite immunosuppressive treatment. No malignant plasmocytosis occurred. The unusual inflammatory muscle infiltration observed in this case may suggest an associated polymyositis. PMID- 1604135 TI - [Neuromuscular complications of D-penicillamine in rheumatoid arthritis]. AB - Between 1979 and 1990 we have seen 8 patients (7 females) with rheumatoid arthritis (RA) who developed a neuro-muscular involvement while on D penicillamine (D.P.). Five of them had a drug-induced myasthenia. D.P. withdrawal led to a complete recovery in 1.5 to 5 months. Another patient presented with a myopathy which led to the diagnosis of Grave's disease. She was treated with D.P. for 4 months. D.P. was reintroduced and 5 months later a myasthenic syndrome developed. A thymoma was discovered 1 year later. In the last 2 patients D.P. induced polymyositis which, in one, was associated with features of systemic lupus erythematosus. In the other patient, the evolution was fatal in spite of D.P. withdrawal, high dose steroids and plasma exchanges. A literature survey has shown 150 D.P. induced myasthenia and 38 D.P. induced polymyositis cases. PMID- 1604136 TI - [Treatment of spasticity with botulinum toxin]. AB - Spasticity following upper motor neuron lesion can be alleviated by few treatments such as physiotherapy, drugs and neurosurgery. However, they all have side effects, limitations or lack of selectivity. We tentatively used the paralyzing effects of botulinum toxin. Since the late 1970's the use of this toxin has increased and it has been extended to numerous muscles and diseases of various causes. In this pilot and open study we use botulinum toxin in spasticity. Eight patients (7 stroke, 1 head injury) with longstanding severe spasticity (minimum: 12 months, maximum: 15 years) were included. Spasticity greatly interfered with their activity in daily life and was resistant to oral antispastic medications. Six patients suffered from pain and 4 had cutaneous lesions especially maceration of the palm of the hand. A-botulinum toxin was injected with a 30-gauged needle. The sites chosen for injection were the following muscles: biceps brachii, brachioradialis, flexor digitorum, flexor carpi, tibialis anterior, flexor digitorum longus. Altogether 41 injections were performed. There were no side effects. Spasticity was improved in all patients. Five patients reported significant pain relief on a visual analogical scale. Most of them reported a benefit in their limb tone and referred to subjective improvement in the activity of daily life and nursing. The beneficial effects of one injection lasted more than 5 months. Seven patients received a second course of treatment. A double-blind study of botulinum toxin in spasticity is to be undertaken to assess its effectiveness and safety when prescribed in the required dose to treat this condition. PMID- 1604137 TI - [Multiple cerebral embolism in acute alcoholic intoxication. A pathological case]. AB - A 37 year-old man sustained 2 ischemic strokes during acute alcohol intoxication. One month after the onset of strokes, a spontaneous atrial flutter occurred. Autopsy revealed an embolic rostral occlusion of the basilar artery. Cardiac verification did not show myocardiopathy or coronary disease. The relations between acute alcoholic intoxication and paroxystic cardiac rhythm disorders are discussed. PMID- 1604138 TI - [Multiple cerebral hemorrhage and amyloid angiopathy of the white matter in a case of Alzheimer's disease]. AB - Amyloid angiopathy is a common pathological finding in Alzheimer's disease. It usually involves leptomeningeal and cortical vessels but spares the white matter. It may cause lobar cerebral hemorrhages at a late stage of the disease. We report a case of Alzheimer's disease at an early stage with diffuse lesions of amyloid angiopathy including some within the white matter, apparently responsible for 2 deep and 1 superficial cerebral hemorrhages. PMID- 1604139 TI - [Eclampsia in the late postpartum. Contribution of x-ray computed tomography and magnetic resonance imaging]. AB - A 28-year-old woman developed late post-partum eclampsia. CT scan showed focal cortical hypodensities and diffuse and bilateral hypodensity of the hemispheric white matter. These lesions were hypointense on T1-weighted sequences and hyperintense on T2-weighted sequences. The CT and MRI abnormalities resolved completely within a few weeks. These changes are similar to those which occur with the more common prepartum eclampsia. PMID- 1604140 TI - [Paralysis of the common oculomotor nerve and contralateral cerebellar syndrome (Claude's syndrome). 2 cases caused by mesencephalic infarction]. AB - Two cases of Claude's syndrome due to a mesencephalic infarction in the territory of the interpedoncular fossa arteries are reported. The first case had pupillary sparing while ptosis was lacking in the second case. Partial impairment of the oculomotor nerve suggests an intra-axial fascicular organization. However, the precise intra-axial pattern of the nerve is unknown in humans. PMID- 1604141 TI - [Activation of deficient right cerebral blood flow by language after global aphasia]. AB - A 39-year old patient abruptly presented with global aphasia. Six years later a mild deficit of articulation and sentence comprehension persisted. A cerebral blood flow study showed that a) during verbal activations, the blood flow increased in the right hemisphere and decreased around the lesion in the left hemisphere; b) the activation was globally higher than in the control group. These data suggest that the right hemisphere plays a significant role in the recovery from aphasia in patients with severe left hemispheric lesions. PMID- 1604142 TI - [Unilateral hydrocephalus caused by abscess of the choroid plexus]. AB - A case of unilateral hydrocephalus due to an abscess in the ipsilateral choroid plexuses, and revealed by intracranial hypertension is reported. Treatment with ceftriaxone, metronidazol and thiophenicol was clinically and radiographically successful, without surgery 3 weeks later. Management and mechanisms are discussed. PMID- 1604143 TI - [Recurrent Neisseria meningitidis meningitis associated with homozygote complement C7 fraction deficiency]. AB - A 20-year old man had three episodes of meningococcal meningitis. Complement assays showed a complete deficiency of the seventh component of the complement system. This case emphasizes the need to perform complement assays in young patients with recurrent bacterial meningitis. PMID- 1604144 TI - [Diseases of the diaphragmatic area. Difficulties of the radiological diagnosis]. AB - Following a reminder of anatomy, the semiology of standard radiology and modern imaging methods is described. The authors then deal with the phrenic-supraphrenic thoracic pathologies (air and liquid effusions, neighbourhood atelectasis, etc.) and with the phrenic-infraphrenic pathologies (transdiaphragmatic hernias, hepatic pathology, subphrenic abscess and pleural effusions). In each of these chapters, the often complex elements of standard radiology and modern imaging methods are detailed. PMID- 1604145 TI - [Tumors of the mediastinal nerves. Diagnosis and possibilities of conservative surgery. Apropos of 2 cases]. AB - Two new cases of tumour of nerves running in the mediastinum are reported; one was a schwannoma of the right phrenic nerve, the other a schwannoma of the vagus nerve. In both cases the diagnosis was suspected on the basis of computed tomography scans. Treatment consisted of nerve-sparing tumour enucleation. The result was incomplete in the first patient, with partial paralysis of the diaphragm, and complete in the second patient, with no disturbance of pharyngeal motility. The authors discuss the diagnosis of these tumours and the validity of nerve-sparing surgery. PMID- 1604146 TI - [Bronchoesophageal cyst in adults. Apropos of a case]. AB - The authors report the case of a 61-year old woman who was operated upon for a paraoesophageal cyst of the bronchogenic type. Having reviewed the French literature on the latest cases, they underline the scarcity of these congenital formations which present as mediastinal cystic tumours with benign expression and course. Computed tomography suggests the diagnosis and reveals the intraparietal site of the cyst. A return to the histogenesis of these cysts makes it possible to understand the nosological distinction with the true bronchogenic cysts and to evaluate the recent classifications. PMID- 1604147 TI - [Mucoepidermoid bronchial carcinoma. Review of the literature apropos of a new case]. AB - Muco-epidermoid bronchial tumours are rare and characterized by the coexistence of epidermoid, mucus-secreting and intermediate cells. The authors report the case of a 22-year old unmarried woman hospitalized for exploration of a febrile dyspnoea related to a right superior lobar atelectasis. Endoscopy showed a smooth, pediculate tumour arising from the right superior lobar bronchus where bronchial biopsy was negative. Right superior lobectomy was performed through thoracotomy and established the diagnosis of muco-epidermoid bronchial tumour. Surgery was followed by radiotherapy of the chest. Over a 5-year follow-up period there was no local or extrathoracic recurrence, and the patient is in good condition. PMID- 1604148 TI - [Endoscopic case: endotracheal hair!]. PMID- 1604149 TI - [Respiration through nasal masks and cutaneous lesions of the nose]. PMID- 1604150 TI - [A case of enalapril maleate intolerance in a negroid patient]. PMID- 1604151 TI - A retrospective on transformation, growth control, and some peculiarities of lipid metabolism. PMID- 1604152 TI - Phospholipases C and D in mitogenic signal transduction. PMID- 1604153 TI - DNA damage-induced gene expression: signal transduction and relation to growth factor signaling. PMID- 1604154 TI - Transcription factor encoding oncogenes. PMID- 1604155 TI - Lysophosphatidic acid: a bioactive phospholipid with growth factor-like properties. PMID- 1604156 TI - Calcium signals in growth factor signal transduction. AB - There is a substantial amount of information which has been obtained concerning the effects of growth factors on [Ca2+]i in proliferating cells. A number of different mitogens are known to induce elevations in [Ca2+]i and some characterization of the Ca2+ response to different classes of mitogens has been obtained. In addition, much is known about whether the Ca2+ response to a particular growth factor occurs as the result of an influx of external Ca2+ or a mobilization of internal Ca2+ stores. In addition, a considerable amount of information is available on the mechanism by which the Ins(1,4,5)P3-sensitive internal Ca2+ store takes up and releases Ca2+. However, there is still a large deficiency in our information concerning other Ca2+ stores in proliferating cells as well as in our knowledge of the mechanisms for regulating Ca2+ entry pathways. Much more data addressing these issues exists for other types of agonist stimulated cells, and we have discussed much of it in this review article. While the wealth of data in nonproliferating cells provides some indications of what mechanisms might be involved in the growth factor-induced changes in [Ca2+]i, it is clear that much work must be done in proliferating cells to fully understand how external factors such as growth factors control [Ca2+]i. In addition, much work remains to be done in identifying the mechanisms for the internal control of [Ca2+]i as cells move through the cell cycle and in identifying the role that these changes in [Ca2+]i may play throughout the cell cycle. PMID- 1604157 TI - [Natriuretic factors]. AB - Atrial natriuretic factor is the main natriuretic hormone. It is a peptide secreted by the atria in response to an increase of the central blood volume. Its effects are opposed to those of the renin angiotensin system and all result in the decrease of volemia. The main of them are an increase in renal sodium excretion, decrease in vascular resistance, increase in capillary permeability, and inhibition of renin and aldosterone secretions. ANF stimulates, via its B receptors, the production of cyclic GMP which is its second messenger. ANF is catabolized by clearance receptors which internalize it and ectoenzymes, mainly neutral endoproteinase. Plasma ANF increases in various conditions for three essential reasons: increase of its secretion from the usual sources, increase of its secretion from supplementary sites, decrease of its catabolism. Since ANF is implied in the maintenance of homeostasis in several diseases, treatment by neutral endoproteinase inhibitors which increases plasma ANF has been considered. Another natriuretic factor structurally close to digitalin and inhibiting Na(+) K+ ATPase has been described but not identified. PMID- 1604158 TI - [Renal functional reserve]. AB - The term "renal functional reserve" (RFR) refers commonly to the reserve of glomerular filtration rate (GFR) and renal blood flow. RFR can be elicited by an oral protein load or by infusion of aminoacids, glucagon, or dopamine. The increase in GFR which follows aminoacid administration results from a cascade of events including at least pancreatic release of glucagon, involvement of an hepatic step yet unidentified, and renal synthesis of vasodilatory prostaglandins. RFR represents a constant fraction of baseline GRF as long as the latter is above 40-50 l/min. It has been suggested tha permanent challenge of RFR, which occurs in protein-rich diet or during the hyperfiltration phase of diabetic nephropathy, might lead to and accelerate impairment of renal function. The relevance of RFR measurement as a tool to predict the evolution of renal function in various types of renal diseases remains to be evaluated. PMID- 1604159 TI - [Kidneys and lipids]. AB - Nephrotic syndrome causes hypercholesterolemia. Chronic renal failure results in hypertriglyceridemia, low HDL cholesterol and, more often, apolipoprotein abnormalities. This dyslipidemia is not corrected by hemodialysis. Transplantation corrects it but leads to other kinds of lipid abnormalities. Whether the treatment of these potentially atherogenetic abnormalities is beneficial of not remains unproved. There is some evidence of lipid contribution to the constitution of glomerulosclerosis in animals but it remains hypothetical in man. PMID- 1604160 TI - [Chronic kidney failure in the elderly]. AB - Ageing does not spare the kidneys but, remarkably, renal impairment is virtually asymptomatic as homaeostasis remains ensured. Nevertheless, in routine practice physicians must take into account the "physiological" renal insufficiency of the elderly. In old people with chronic renal impairment the diagnostic and therapeutic approaches are special, owing to the age-related risks attached to both paraclinical examinations and treatments. Yet in certain subjects treatment can be remarkably effective and prevent the progression to terminal uraemia, and this justifies the detection and exploration of renal insufficiency in elderly patients. In the last few years, iterative dialysis programmes have been made available to third or even fourth age patients who had reached the so-called end stage renal failure. The results are encouraging, but there are still purely medical questions concerning the measures to be taken in priority and the numerous organization problems to be solved for optimal management of these patients. PMID- 1604161 TI - [The heart in chronic kidney failure patients]. AB - Risk factors for heart disease in patients with chronic renal failure (CRF) are the same as in general population; moreover CRF and renal replacement therapies (dialysis, immunosuppressive drugs for kidney transplantation) induce further specific cardiac risks. In practice, the commonest heart diseases associated with CRF are coronary artery diseases, myocardiopathies from various aetiologies, valve diseases and arrhythmias. Uremic pericarditis are quite unusual nowadays. Advances in therapy authorize easier control of congestive heart failure, the major complication of heart disease in CRF patients. Furthermore, it was observed that correction of anemia with erythropoietin therapy or kidney transplantation can ameliorate or reverse partially some cardiac diseases. PMID- 1604162 TI - [Recombinant human erythropoietin in uremic patients in substitute treatment]. AB - The recent availability of Recombinant Human Erythropoietin (EPO) has radically stirred-up diagnosis and therapeutical approach of anemia in dialysis patients. By correcting anemia in a dose related manner in virtually all dialysis patients, clinical use of EPO has confirmed its remarkable efficiency. Correction of anemia marked by a rapid improvement in "well being" of patients is also objectively associated with the correction of most of the debilatating multiple organs dysfunction due to the uremic state. Hypertension is one of the more frequent and worrying complication associated with EPO therapy. Optimal use of EPO, integrating administration route and frequency of injections, will reduce the EPO doses needed and minimize cost and side-effects incidence. EPO represents a major advance in the treatment of chronic uremia. EPO opens a new therapeutic era offering for the first time a substitute to a kidney endocrine failure. PMID- 1604163 TI - [Optimization of renal transplantation]. AB - In 1990, 1,949 renal transplantations were performed in France, with a graft survival rate of 89% at one year and 70% at five years. To improve on these results it would be necessary to pursue a dynamic policy in all fields of transplantation: in view of the ever growing number of patients on the transplantation list, more kidneys should be collected; hyperimmunized recipients should undergo reinforced exchanges to have compatible kidneys; immunosuppression must be optimized: just a using cyclosporin and monoclonal antibodies has resulted in a significant advance, so should the discovery of new drugs, such as FK 506, or of more specific monoclonal antibodies, be a source of progress; the complications of immunosuppression must be controlled: prevention protocols and antiviral treatments have considerably reduced the incidence of viral infections. The emergence of malignant tumours directly related to the degree of immunosuppression can be prevented by a rational use of immunosuppressants and by systematic detection. All these advances make it possible to extend the indications of renal transplantation to subjects at risk, notably patients more than 60 years old, and diabetic patients who can successfully benefit from a dual kidney-pancreas transplantation. PMID- 1604164 TI - [Reflux nephropathy]. AB - Reflux nephropathy is characterized by the presence at radiological examination of one or several segmental scars in the renal parenchyma, associated with vesico ureteral reflux. Histology displays a variety of lesions, among which chronic and atrophic pyelonephritis, segmental hypoplasia and renal dysplasia can be individualized. Most of these renal lesions can be prevented by early detection of the reflux which encourages the development and recurrence of urinary tract infection and its diffusion to the upper urinary tract and the kidneys. The finding of a vesico-ureteral reflux with renal lesions, even after spontaneous or surgical regression of this reflux, requires prolonged surveillance in view of the long-term risk of arterial hypertension and renal failure. PMID- 1604165 TI - [Endobronchial prostheses. Therapeutical endoscopy increased their indications]. PMID- 1604166 TI - [Magnetic cortical stimulation. A new means of exploration of the nervous system]. PMID- 1604167 TI - [Screening for breast cancer. Is mass screening possible in France?]. PMID- 1604168 TI - [Respiratory complications of massive obesity]. AB - Massive obesity may lead to serious, and sometimes fatal, respiratory complications. Alterations of ventilatory mechanics and function are well known; they include a decrease in respiratory compliance, an increase in ventilatory work and a restrictive pulmonary disease. Hypoxemia is rather due to an impaired ventilation/perfusion ratio than to alveolar hypoventilation. Sleep Apnea Syndrome (SAS) is very frequent in excessively obese patients. These subjects with daytime hypersomnolence should be systematically screened for SAS before the occurrence of life-threatening complications. Continuous positive airway pressure ventilation through a nasal mask is the treatment of choice of SAS especially since the results of body weight reduction and ENT surgery are inconstant and variable in these patients. PMID- 1604169 TI - [Critical reading of medical papers. VI. Application field and limits]. PMID- 1604170 TI - [The French Pancreas Club]. PMID- 1604171 TI - [AIDS and adoption]. PMID- 1604172 TI - [Inflammation. Morphology and physiopathology]. PMID- 1604173 TI - [Salivary lithiasis. Diagnosis, principles of the treatment]. PMID- 1604174 TI - [Atrial fibrillation and flutter. Etiology, physiopathology, diagnosis, development, prognosis, principles of the treatment]. PMID- 1604175 TI - [Purulent meningitis. Meningitis excluding immunodeficiency pathology: epidemiology, etiology, diagnosis, development, prognosis, prevention, principles of the treatment]. PMID- 1604177 TI - [Hyperkalemia. Etiology, physiopathology, diagnosis, principles of the treatment]. PMID- 1604176 TI - [Influenza. Epidemiology, etiology, physiopathology, diagnosis, treatment, prevention]. PMID- 1604178 TI - [Angiotensin-converting enzyme inhibitors. Principles and rules for their use]. PMID- 1604179 TI - [Enlarged kidney in children. Diagnostic orientation]. PMID- 1604180 TI - [Anemia in children. Diagnostic orientation]. PMID- 1604181 TI - [Clinical diagnosis of sciatica]. AB - Sciatica is diagnosed on purely clinical grounds. The initial clinical examination provides the main elements for an aetiological diagnosis. It makes it possible in certain cases to take urgent decisions: to prescribe imaging methods or specific treatments. When examining patients suffering from sciatica, the clinician must aim at gathering elements of answers to the following questions: Is the diagnosis of sciatica ascertained? Is it a common vertebral disc sciatica? Is surgery urgently required? What is the personal and medico-social context? PMID- 1604182 TI - [Imaging in sciatica]. AB - Sciatica being a benign disease its outcome is usually favourable, and paraclinical examinations should hold a modest role in its exploration, notably in the first painful episode. In reality, for multiple social, occupational and economic reasons imaging often intervenes at a very early stage of the condition. The role of standard radiography is to exclude non-discal diseases, and it should not need to be repeated in young adults. Computed tomography should be used only after a well-conducted treatment of six to eight weeks duration to demonstrate the responsible discal herniation and its morphological features in order to guide the therapeutic approach. Radiculography should no longer be performed as a first-line examination, but in about one out of ten cases it may be interesting to confirm an uncertain nerve root compression and, above all, to visualize in a standing up patient a container-contained maladjustment such as, for example, a vertebral canal stenosis. Magnetic resonance imaging, a rational, accurate and non-invasive method, unfortunately cannot be used as first-line examination due to its reduced accessibility in France. PMID- 1604183 TI - [Narrow lumbar canal]. AB - The diagnosis of spinal stenosis can be strongly suspected when the following symptoms are present: limbs neuralgias with a poorly defined location, paresthesias in several dermatomas neurogenic intermittent claudication. Myelography coupled with scan yields the best information about morphology, levels of stenosis and narrowing factors, bone bridges ligaments and discal structures. If surgery is decided after failure of medical treatment to improve the patient's condition, the choice will be best guided by the myeloscan analysis. PMID- 1604184 TI - [Surgical treatment of radicular sciatica]. AB - The surgical treatment of radicular sciaticas has to be fitted to the patient's mainly functional problem. In every case but the obviously surgical sciaticas due to tumor, surgery and percutaneous techniques must be discussed with regard to the anatomical factors participating in the root compression and the patient tolerance to his pain. The surgical approach is now limited but the disc removal must be extensive. Complications are very rare, especially infectious ones. Failures account for less than 10% in case of good indications and are related to recurrence of disc herniation and to so-called fibrosis. The operative results are to a large extent related to the patient's psychological profile and his active involvement in the treatment. PMID- 1604185 TI - [Recurrences and pseudo-recurrences]. PMID- 1604186 TI - [Apomorphine and Parkinson's disease. A major therapeutical progress]. PMID- 1604187 TI - [Hormones and sleep. Each hormone at its own rhythm!]. PMID- 1604188 TI - [Numerical systems in conventional radiology. Value in pediatrics]. PMID- 1604189 TI - [Circulating anticoagulants, antiphospholipids and thrombosis]. AB - Antiphospholipids are auto-antibodies which can be detected both by immunological assays and by prolongation of coagulation test times. The latter has lead them to be called "lupus anticoagulant". They act preferentially on anionic phospholipids. Their presence increases the risk of thrombosis, especially in LED. They can appear at all ages, spontaneously, in autoimmune, infectious, or neoplastic pathologies, or after the intake of certain drugs. When these antibodies are associated with thrombosis or repeated fetal loss, the "antiphospholipid syndrome" is evoked. No causal relationship between the presence of these antibodies and thrombosis has yet been demonstrated. Standardization of laboratory diagnosis is not easy, particularly for weak positive samples. Because of their heterogeneity, an association of several tests is required for detection. PMID- 1604190 TI - [Leprosy. Developmental modalities]. AB - The very broad clinical spectrum of the Mycobacterium leprae infection is due to the diversity of the underlying immunological and genetic factors. The evolutive modalities of leprosy are mainly determined by a dual pathogenesis: An infectious disease due to a bacillus of low virulence which, even when dead, persists in the body for several years, independently of the antibiotic therapy prescribed. A dysimmune disease maintained by a chronic discharge of antigens. Neuropathies and leprous reactions are still the most troublesome episodes in the course of the disease. They constitute the principal prognostic factor in both pauci- and multibacillary forms of leprosy. PMID- 1604191 TI - [Memories of the infectious diseases "pavillons" of the Public Assistance in Paris between the two wars]. PMID- 1604192 TI - [Hepatitis B. Epidemiology, etiology, diagnosis, development, prognosis, principles of treatment]. PMID- 1604193 TI - [Urogenital Gonococcus and Chlamydia infections (except Nicolas-Favredisease). Epidemiology, diagnosis, clinical course, principles of treatment]. PMID- 1604194 TI - [Polycythemia vera. Diagnostic orientation]. PMID- 1604195 TI - [Acute renal failure. Etiology, physiopathology, diagnosis, principles of the treatment]. PMID- 1604196 TI - [Monitoring of patients in plaster casts]. PMID- 1604197 TI - [Neurotic syndromes: phobic neurosis. Diagnosis, principles of the treatment]. PMID- 1604198 TI - [Prenatal protection. Regulation. Perinatal mortality. Epidemiology]. PMID- 1604199 TI - [Asthma in children. Physiopathology, diagnosis, clinical course, prognosis, principles of the treatment]. PMID- 1604200 TI - [Genetic predisposition to cancer]. AB - Epidemiological studies indicate that environmental factors are more important for cancer development than inherited factors. However, clinical observations such as familial cancer clustering, constitute compelling evidence to the existence of inherited susceptibility to cancer. Few cancer-predisposing genes have been identified so far, by hard laboratory work and with the help of molecular biology tools. The predisposing genes that have been cloned can be used for DNA-based diagnosis. Genes inherited in altered form in familial cancers are the same genes that are altered in somatic cells of individuals with sporadic cancers. Identification of cancer genes through the study of rare families in which susceptibility to cancer is inherited, could have important consequences for diagnosis and treatment of common cancers. PMID- 1604201 TI - [Osteosarcoma]. AB - Osteosarcoma is the most frequent malignant tumor of bones. The peak incidence is in the second decade and the metaphyseal part of long bones is the site of predilection. This tumor is spontaneously rapidly fatal but recent progresses in chemotherapy and surgery have improved its prognosis (for example initial chemotherapy with high dose methotrexate and postoperative chemotherapy adapted to the histological response of the resected tumor to preoperative treatment). PMID- 1604202 TI - [Ewing's tumor]. AB - Ewing's tumour is an undifferentiated round-cell sarcoma of children and adolescents arising from the skeleton. The translocation (11; 22) (q24; q12) is specific and could serve as a diagnostic marker. It has also enabled this tumour to be classified in the group of primary neuro-ectodermal tumours. Concerning treatment, intensive chemotherapy alternating with local therapy has improved the prognosis of localized Ewing's sarcoma of the limbs and, to a lesser degree, of the axial skeleton. PMID- 1604203 TI - [Neuroendocrine tumors]. AB - The original classification of neuroendocrine tumours proposed by Pearse was based on a common embryologic origin in the neuroectoderm. This is being replaced by other classifications based on results of modern techniques: secretory granules shown by electron microscopy, neuroendocrine tumour markers (NSE, chromogranin A, NPY ... ) shown by immunocytochemistry and blood measurements. Most endocrine tumours are single and sporadic, but in some patients they are multiple and/or occur as a familial disease such a multiple endocrine neoplasia or other disease, the transmission of which is autosomal dominant. This permits a more reliable classification of tumors, that can be used to determine their prognosis and response to therapy. PMID- 1604204 TI - [Unremitting otitis, subacute mastoiditis. Diagnostic difficulties, importance of the course of the treatment]. PMID- 1604205 TI - [Contrast agents in magnetic resonance. From gadolinum complexes to superparamagnetic spinels]. PMID- 1604206 TI - [Crohn's disease. When is surgery indicated?]. PMID- 1604207 TI - [Drug therapy of diabetic retinopathy. The beginning of hope?]. PMID- 1604208 TI - [Angioplasty of coronary arteries in chronic coronary insufficiency]. AB - During the past five years transluminal angioplasty of the coronary arteries has considerably developed due to the improvement of the technology. Beside one vessel lesions, its indications have been extended to multiple vessel pathology, chronic obturation and lesions found in patients who had previously undergone aorto-coronary bypass, as well as in those who had unstable angina, or in the elderly. Despite the quality of the initial results and the relatively low accident rate, this method has raised numerous problems: (I) unintentional optimization of the results, (II) unexplained postangioplastic incidents, (III) high rate of early restenosis, (IV) encouraging long-term results but marked by numerous coronary "events", (V) increasing cost of the procedure, (VI) disappointing resumption of work and, above all, (VII) lack of good randomized trials to establish the exact indications of angioplasty in the treatment of chronic heart failure. The new techniques of cardiocirculatory assistance or excision of atheroma have only started to be evaluated. PMID- 1604209 TI - [Sterility and medically assisted fertilization]. AB - In vitro fertilization is now part of the treatment of infertility. Since 12 years, indication have been extended to male or female infertility factors. The successes have also been increased and the actual pregnancy rate is about 18% pregnancies by retrieval. Different methods are available such as GIFT, ZIFT, TET and progresses will certainly come from new techniques such as micro manipulation, oocyte freezing and genetic procedures applied to assisted reproduction technologies. PMID- 1604210 TI - [Topographical distribution of the adipose tissue and its pathological impacts]. PMID- 1604211 TI - [The sad death of the good doctor Budin]. PMID- 1604212 TI - [Mitral valve stenosis. Etiology, physiopathology, diagnosis, clinical course]. PMID- 1604213 TI - [Whitlow and phlegmon of the tendon sheaths. Diagnosis, clinical course, prognosis, principles of treatment]. PMID- 1604214 TI - [Hyperthyroidism. Etiology, physiopathology, diagnosis, clinical course, prognosis, principles of treatment]. PMID- 1604215 TI - [Myeloma. Physiopathology, diagnosis, principles of treatment]. PMID- 1604216 TI - [Myelocytosis in adults. Diagnostic orientation]. PMID- 1604217 TI - [Deafness. Diagnostic orientation]. PMID- 1604218 TI - [Blunt injuries of the thorax. Physiopathology, diagnosis, principles of treatment]. PMID- 1604219 TI - [Manic syndrome. Diagnostic orientation and principles of treatment]. PMID- 1604220 TI - [Pressure sore. Etiology, physiopathology, prevention]. PMID- 1604221 TI - [Comparative effects of sodium fluoride and hormonal replacement therapy on bone metabolism in osteoporotic women with high fracture risk. Results of monitoring for 2 years]. AB - Thirty seven postmenopausal women aged under 65 with densitometric osteoporosis defined by a bone density value below the 80th percentile of the osteoporotic population but without identifiable crush fractures, were treated and monitored for two years using clinical, laboratory and densitometric parameters. Sixteen of them were given hormonal replacement therapy combining percutaneous or transdermal 17 beta estradiol with a progestogen and the other 21 sodium fluoride at the dose of 50 mg/d combined with calcium and vitamin D. There was a significant increase in vertebral bone density in both groups: 6.3 +/- 0.9 per cent for hormone treatment and 7.1 +/- 1.5% for fluoride after 2 years, while it fell in a control group. The increase was linear with fluoride, while 2/3 of the gain was acquired by the end of the first year of hormonal therapy. Nine of the 16 patients on hormonal therapy and 9 of the 21 taking fluoride showed a significant vertebral gain at 2 years (greater than or equal to 0.043 g/cm2). There was no parameter which enabled the identification of "responders" before treatment. There was no difference in changes in femoral bone density between patients treated with fluoride and controls. From a laboratory standpoint, hormonal therapy caused a significant fall at 12 months in the urinary calcium/urinary creatinine ratio, and a non-significant fall in osteocalcin at 2 years. With fluoride, there was a marked rise in osteocalcin and a more moderate rise in alkaline phosphatase, reflecting stimulation of bone formation without any variation in resorption. In conclusion, this study shows the ability of both these types of treatment of increasing, by different mechanisms, the vertebral bone density of osteoporotic women. However, it does not indicate the extent to which this gain in bone density might have a positive influence on fracture risk. PMID- 1604222 TI - [Complete and dissociated forms of Poland's syndrome (5 cases)]. AB - The authors report 5 cases of aplasia of pectoralis major including 2 associated with a malformation of the hand falling within the context of Poland syndrome, which is a relatively common congenital malformation consisting of an association in varying degrees of hypoplasia of pectoralis major and a complex malformation of the homolateral hand. The pathogenesis of this malformation is gradually emerging and while familial cases have been reported, the majority of Poland syndromes are sporadic. The hypothesis involving interruption of the embryonic blood supply of the subclavian arteries during a critical period of embryonic development at about the 46th day is the most attractive. This hypothesis also enables extension of the manifestations seen to other congenital malformation syndromes. However, it could be disproved in one of our cases and the notion of early embryonic damage was more plausible. PMID- 1604223 TI - [Alpha-1-antitrypsin deficiency in chronic inflammatory rheumatism and mechanical arthropathies. Preliminary results]. AB - Alpha-1-antitrypsine (AAT) plasmatic level is higher (p less than 0.01) in 85 chronic inflammatory arthropathies than in 238 non inflammatory arthropathies (2.5+/0.7 versus 2.1+/0.4 g/l). Among 15 rheumatoid arthritis (RA) with evaluated phenotype, alleles M2 are less frequent and M3 more frequent than in 22 non inflammatory arthropathies (p less than 0.02). Some abnormal phenotype are observed: M2Z (AAT = 1.7) without pulmonary involvement (1 RA); M3S in 2 seronegative spondylarthropathies (1 pulmonary involvement without tobacco intoxication: DLCO/VA: 69% of theoric value; AAT = 1.4); ZZ in a systemic lupus erythematosus with panlobular emphysema and hepatic cirrhosis (AAT = 0.4). An AAT deficiency could explain some pulmonary involvements in chronic inflammatory arthropathies. PMID- 1604224 TI - [Vertebral hydatidosis. Complications, contribution of modern imaging]. AB - Vertebral hydatidosis is the commonest skeletal manifestation of echinococcosis. It is also the most serious: among 6 patients followed-up for a mean period of 10 years, all had neurological complications and only one is free of neurological sequelae at the present time (at the price of multiple spinal operations). While current medical treatment remains essential, it does not always control this skeletal parasite infestation which requires careful monitoring (CT scan, NMR) in order to detect and treat all possible recurrences. PMID- 1604225 TI - [Cranial vault meningioma. Apropos of 3 cases]. AB - The authors report three different types of cranial bone lesions due to a meningioma of the convexity. This rare tumour is most often benign, with variable radiological appearances. The diagnosis is often suggested by tangential views of the cranial vault and CT scan but meningioma remains a histological diagnosis, notably in its primary intra-osseous form without actual meningeal involvement. The prognosis is good and the risk purely local, by vascular or cerebral compression. Treatment is surgical, sometimes complicated by recurrence. PMID- 1604226 TI - [Osteonecrosis, metastases and bronchial carcinoid]. AB - The authors report the case of a 35-year-old woman undergoing surgery in 1976 for a bronchial carcinoid tumour, considered to be benign. Twelve years later, diagnostic evaluation of liver metastases led to the discovery of an asymptomatic lesion of D10, the CT scan and NMR appearances of which were suggestive of osteonecrosis, a diagnosis confirmed histologically. Investigations were repeated 2 years later because of spinal pain. While NMR and CT scan remained compatible with bone necrosis, biopsy on this occasion confirmed the presence of carcinoid tumour. These rare tumours metastasise little. Secondary bone deposits, essentially axial, are of an osteoblastic nature. The lesion seen in our patient was closer to idiopathic bone infarcts or those associated with Gaucher's or sickle cell diseases than to classical vertebral osteonecrosis. The relationship between vertebral necrosis and metastasis remains obscure. PMID- 1604227 TI - [Giant synovial cyst of the shoulder. Apropos of a case]. AB - Synovial cysts of the shoulder are rare. The case described illustrates the particular problems encountered at this site. As at other joints, these cysts appear during arthropathies of various types: degenerative or inflammatory (rheumatoid arthritis). They are often associated with rupture of the rotator cuff. Their essential characteristic is an expansive and recurrent tendency which leads to striking giant swellings, capable of causing vascular compression. Treatment involves surgical excision. This suffices when the cyst does not communicate with the joint cavity. In contrast, when there is a breach in the capsule through which the cyst derives its synovial fluid supply, repair is necessary to prevent recurrence. PMID- 1604228 TI - [Primary Nocardia asteroides deltoid abscess in treated Horton disease]. AB - In a patient treated with high doses of corticosteroids for giant cell arteritis, a renewed rise in sedimentation rate accompanied by painful limitation of mobility of the shoulder led to the discovery of an intra-deltoid fluid collection. Aspiration yielded pus, culture showing the presence of Nocardia asteroides (NA). No portal of entry nor extramuscular sites of infection were found, justifying a diagnosis of primary nocardial muscle abscess. To the best of our knowledge, this is the first reported case. The opportunity is taken to review the epidemiological and clinical characteristics of NA infections as well as new management approaches. PMID- 1604229 TI - [Polymyalgia rheumatica and pulmonary cancer: paraneoplastic syndrome]. AB - An 83-year-old lady was admitted for bilateral pain and weakness of the shoulder and hip girdles. These symptoms suggested a Polymyalgia rheumatica (PMR) but there was no response to corticosteroids. A pulmonary adenocarcinoma without any metastasis was then diagnosed. The excision of this tumor was followed by prompt and complete recovery. The erythrocyte sedimentation rate became normal within a few days, also. Such an issue seems to prove that PMR may occasionally be associated with neoplasia. This association appears anecdotal in the literature and remains without clear explanation. PMID- 1604230 TI - [Coexistence of monoclonal IgM and ankylosing spondylitis. Apropos of 2 cases]. AB - Two cases of the association of monoclonal IgM and ankylosing spondylitis are reported. Their presentations are in accordance with local epidemiological data (monoclonal IgM, both kappa, one of them malignant, discovered in 71 and 79 year old men). Ankylosing spondylitis does not appear as either favouring the incidence of monoclonal immunoglobulins or, in our opinion, having a major influence on their isotype. Conversely, while each member of this association could have its own story, the possible role of the coexistence of HLA B27 together with ankylosing spondylitis should be considered. PMID- 1604231 TI - [Fracture caused by bone insufficiency of the sternum simulating myocardial infarction]. PMID- 1604232 TI - [Value of pulse methylprednisolone in polyarticular forms of psoriatic rheumatism]. PMID- 1604233 TI - [3 cases of Achilles tendinitis caused by pefloxacin, 2 of them with tendon rupture]. PMID- 1604234 TI - [Stop intra-disk injections of corticosteroids]. PMID- 1604235 TI - [Lower limb arteriopathy and male osteoporosis]. AB - There are close links between bone metabolism and bone circulation. Osteoblasts are derived from the walls of the venous sinuses. As shown by Burkardt, osteoporosis is accompanied by a decrease in the number of intra-osseous capillaries, and intra-osseous arterioles may be the site of arteriosclerosis lesions. In order to determine the existence of a possible link between arteriosclerosis and male osteoporosis, the etiology of which is often poorly defined, the authors studied phosphorus-calcium balance, X-rays of the spine, and bone density of the spine and the femoral neck in 17 male arterial disease sufferers with a mean age of 61 and at Leriche stage 2, 3 or 4. These 17 patients were compared with 15 age-paired controls. Wedge fractures, absent in the control group, were seen in 9 of the 17 patients. Bone mineral content in the femoral neck was significantly reduced in the arterial disease group. PMID- 1604236 TI - Lymphocyte recirculation: the need for site-specific receptors to dictate T lymphocyte localization into different tissue sites. AB - This paper addresses the need for receptors involved in recirculation of T lymphocytes both during development and during an immune response or inflammation. Some known receptors present on T lymphocytes which are important in maintaining normal T-cell localization and function, i.e. the integrins, LECAMs, LPAM-1 and H-CAM (CD44) are considered in terms of the specificity which they confer on lymphocyte recirculation. A clear understanding of lymphocyte trafficking patterns and of the receptors involved may provide, for example, novel therapies for treatment of malignant cancer, alleviation of damage caused by lymphocytes during inflammatory responses, and targeting of cells to sites of infection. PMID- 1604237 TI - Secretion of macrophage fusion factor (MFF) by schistosome egg granulomas maintained in vitro. AB - The schistosome granuloma cultured in vitro under antigenic specific and unspecific stimulation releases macrophage fusion factor (MFF) into the medium, adjusting the production dynamics to the spontaneous modulation model already described. These findings demonstrate the feasibility of studying granulomatous response in mammalian schistosomiasis utilizing an in vitro model of lymphokine granuloma secretion. PMID- 1604238 TI - Soluble interleukin-2 receptor levels and immune activation in patients with schistosomiasis and carcinoma of the urinary bladder. AB - Soluble interleukin-2 receptor (sIL-2R) level in serum is a marker of immune regulation and lymphocyte activation. Highly elevated levels of sIL-2R in serum were observed in patients of schistosomiasis with carcinoma of the bladder (SCB) and carcinoma of the bladder without schistosomiasis (CB) compared with patients with carcinoma of the prostate with or without schistosomiasis and normal healthy controls. Patients with SCB, who had an elevated percentage of cells expressing CD38+ activation antigen and CD71+ transferrin receptors in circulation, also had elevated levels of sIL-2R in serum. There were few interleukin-2 receptor (CD25+) positive cells in circulation in some patients with SCB. Despite this, the sIL-2R levels were extremely elevated. Our data suggest that in SCB, CD38+ and CD71+ cells may be the source of secretion of sIL-2R in serum. This relationship was confirmed by phenotypic characterizations of mononuclear cells and sIL-2R levels in individual patients. Measurements of sIL-2R levels in serum may provide a sensitive method of immune activation in patients with SCB. PMID- 1604239 TI - Complete amino acid sequence of the variable regions of two highly related heavy and light chains of human IgG (SFL) and IgM (RIV) rheumatoid factors. AB - The complete amino acid structure of the variable regions of two monoclonal human rheumatoid factors (RF), antibodies that bind to the Fc portion of IgG, is presented. Although these RFs are of different isotypes, IgG (SFL) and IgM (RIV), they are highly related. They probably derive from the same KIII light chain variable region used, but the heavy chains are derived from genes of the VHIII family that are probably evolutionarily related. An analysis of the level of somatic mutation reveals that antigen selection was probably involved in the maturation of these clones. These antibodies, although highly related, are not merely IgM to IgG switch variants which occurred independently in different individuals. Little is currently known about the structure of IgG RFs and this study indicates that the level of somatic mutation of SFL is similar to other autoantibodies or antiviral antibodies of the IgG isotype. PMID- 1604240 TI - Histamine modulates the interleukin-6-regulated acute phase protein synthesis in cultured murine hepatocytes. AB - Murine hepatocytes cultured in the presence of human recombinant interleukin-6 (IL-6) show increased synthesis of fibrinogen and complement component C3 by the addition of histamine. No similar effect was achieved when murine hepatocytes were treated with histamine alone or with histamine and interleukin-1 alpha together. Using histamine-1 (H1) and H2 receptor antagonists a prevalence of histamine H1 receptor in the enhancement of IL-6-induced effect is suggested. PMID- 1604241 TI - The effect of non-immune IgG on antigen-antibody complexation. AB - Two preparations of human IgG, one acylated with beta-propiolactone (acylated IgG) and one treated at pH 4 with traces of pepsin (pH 4-IgG), were used to study the effect of non-immune IgG on antigen-antibody interactions in the antigen excess zone. Employing two immunological methods together with size-exclusion chromatography, we found that the formation of human albumin-rabbit anti-human albumin complexes was inhibited in the presence of human IgG. In addition, IgG seemed to promote the aggregation of already formed complexes. Thus, non-immune IgG may modulate immune complexation by direct molecular interactions. The effect was dependent on the size and composition of the immune complexes as well as on the conformation of the IgG molecules with respect to their shape, isotype, charge, and other surface properties. Some possible mechanisms for the reactions are discussed. PMID- 1604242 TI - M. tuberculosis-complex specific T-cell stimulation and DTH reactions induced with a peptide from the 38-kDa protein. AB - An immunodominant T-cell-stimulatory epitope located near the carboxy terminus of the 38-kDa antigen from M. tuberculosis (38.G, residues 350-369) was found to be M. tuberculosis-complex specific. This was demonstrated by the presence of proliferative and delayed type hypersensitivity (DTH) responses in mice immunized with Mycobacterium tuberculosis and Mycobacterium bovis BCG, whereas mice immunized with M. avium or other non-tuberculous species of mycobacteria showed no such responses. Peptide 38.G stimulated the proliferation of peripheral blood lymphocytes from healthy purified protein derivative (PPD)-positive individuals but not from PPD-negative individuals. It also elicited DTH responses in M. tuberculosis sensitized mice and in PPD-positive healthy human volunteers. Peptide 38.G could therefore prove to be an important component in any new molecularly defined reagent used in the immunodiagnosis of tuberculous infection. PMID- 1604243 TI - Immunoglobulin levels during follow-up of children with selective IgA deficiency. AB - Longitudinal serum immunoglobulin levels were studied in 36 children with selective IgA deficiency during a median follow-up period of 5 years. Twenty-five children were 'sporadic' cases, and 11 were 'familial'. Serum and saliva IgA levels in 23 children remained below 2 mg/l. Eight children with IgA levels above 2 mg/l showed considerable intra-individual variance in serum IgA, but remained IgA deficient. Five children at various ages developed IgA levels above 50 mg/l with detectable secretory IgA in saliva. In most of the children IgG subclass levels were found to be rather high, including at younger ages. There were no obvious differences between 'sporadic' and 'familial' cases except an association between IgD deficiency and serum IgA levels below 2 mg/l, and between serum levels of IgD above 1 IU/ml and of IgA above 2 mg/l, which was found to be significant in the 'sporadic' group but not in the 'familial' group. PMID- 1604244 TI - Immune events in skin. I. Spontaneous cluster formation of dendritic (veiled) cells and lymphocytes from skin lymph. AB - To investigate the mechanism of spontaneous attachment of afferent lymph lymphocytes to dendritic cells, cells from canine skin lymph were used. There were 3.3 +/- 2.8% of veiled cells in clusters found in lymph flowing from the cannulated lymph vessel. The number of clusters forming ex vivo in the collected lymph samples increased as a function of time and was temperature dependent. Incubation of cells with proteolytic enzymes or monosaccharides did not alter cell interactions. The ability of veiled cells to bind lymphocytes was independent of divalent cations but reduced by xylocaine and retinoic acid. Among steroids only methylprednisolone showed an inhibitory effect on cluster formation. Indomethacin and acetylsalicylic acid had no blocking activity on cell binding. Also, no effect was seen after treatment with cyclosporine A and azathioprine. An enhanced cluster formation after desialation with neuraminidase was observed. The desialated cells were cultured in order to study their stimulatory and accessory cell functions. No enhancement of autologous mixed leucocyte reaction was seen, but a significantly higher responsiveness to a suboptimal dose of phytohaemagglutinin was observed. The N-ase-mediated non specific cell attachment could be abrogated by cell washing or treatment with EDTA or xylocaine. This study indicates that cluster formation by skin lymph veiled cells and lymphocytes is a spontaneous process which cannot be controlled by means usually effective in regulating the in vitro induced clustering of antigen-stimulated cells. PMID- 1604245 TI - Western blot analysis of human IgG reactive with the collagenous portion of C1q: evidence of distinct binding specificities. AB - An enzyme-linked immunosorbent assay (ELISA) with purified collagenous C1q fragments in the solid phase was used for detection of C1q-specific immunoglobulins in the sera of twelve patients with systemic lupus erythematosus (SLE) or the SLE-like disease hypocomplementemic urticarial vasculitis syndrome (HUVS). By clinical criteria, four patients had SLE, and three HUVS. Five patients had overlap syndromes. All patients demonstrated high concentrations of C1q-specific IgG and markedly low concentrations of circulating C1q. Detection of C1q-specific IgG in SLE sera was facilitated by employment of saturating concentrations of collagenous C1q fragments in the solid-phase ELISA. When added to SLE serum, immune complex-fixed C1q inhibited binding of IgG to the C1q fragments, whereas addition of C1q alone had limited inhibitory effects. Under similar conditions, using approximately equimolar amounts of C1q relative to solid-phase C1q fragments, no ELISA inhibition was obtained after addition of C1q or immune complex-fixed C1q to a HUVS serum. Even in large excess, purified C1q did not inhibit binding of HUVS-IgG to solid-phase C1q fragments. Thus, possible interactions between HUVS-IgG and native Clq are probably of low affinity. By Western blot analysis, IgG reactive with the B and C chains of C1q was found in the eight patients with evidence of HUVS, five of whom also showed IgG binding to C'-C' and A'-B' dimers of collagenous C1q fragments. Sera from SLE patients were negative by Western blot analysis. It seems likely that C1q-specific IgG in SLE primarily recognizes assembled C1q molecules or collagenous C1q fragments expressing conformational epitopes of bound C1q. Interestingly, patients with evidence of HUVS fairly consistently had zymogen (C1r-C1s)2 complexes in their serum, while patients with SLE showed high concentrations of complexes containing Cl inhibitor, C1r and C1s. Different binding specificities of C1q-reactive IgG could be of importance with regard to pathogenetic mechanisms in SLE and HUVS. There was no correlation between findings of C1q-specific IgG and a variety of autoantibodies associated with SLE and SLE-like disease. PMID- 1604246 TI - Human germinal centre B cells inhibit mitogen-induced proliferation of mantle zone B cells. AB - Lymphoid follicles are the main B-cell areas in peripheral lymphoid tissues. These structures commonly consist of germinal centre (GC) and mantle zone (MZ) regions. In the present work, human tonsillar B cells belonging to these two compartments were purified by a combination of density centrifugation and separation techniques involving the recognition by monoclonal antibodies of specific surface molecules followed by panning and magnetic bead selection. These purified populations were identified as GC and MZ cells by three different criteria: (1) GC cells showed the phenotype IgD- CD20+bright CD38+ CD44- and peanut agglutinin (PNA)+, and MZ cells were IgD+ CD20+dim CD38- CD44+ and PNA-; (2) morphologically, MZ cells appeared as small resting lymphocytes whereas GC cells consisted of large blastic cells of the germinal centre; (3) functionally, most GC, but not MZ, cells underwent apoptosis early in culture. The isolation of GC and MZ cells allowed the study of their proliferative response. As a result of these studies, GC cells were demonstrated to inhibit the proliferation of MZ cells in response to B-cell mitogens (Staphylococcus aureus Cowan I and anti-mu plus BCGF) in a concentration-dependent way; 50% inhibition was reached at a GC/MZ cell ratio of 1/2. This effect did not require GC-cell DNA synthesis since similar results were obtained with irradiated GC cells. Neither was it due to a non-specific toxic effect since GC cells did not alter the proliferative response of autologous T cells to mitogens (phytohaemagglutin and anti-CD3). The inhibition required cellular contact between GC and MZ cells, and was not restricted by histocompatibility barriers. These data suggest the possible existence of a new regulatory pathway within peripheral B-cell areas. PMID- 1604247 TI - Molecular mimicry, ankylosing spondylitis and reactive arthritis--something missing? PMID- 1604248 TI - A monoclonal antibody recognizing Golgi apparatus produced using affinity purified material from a patient with connective tissue disease. AB - Serum antibodies recognizing the Golgi apparatus have been reported in patients with connective tissue diseases, but little is known of their significance. Serum from a systemic lupus erythematosus patient with polymyositis was found to have high titers of anti-Golgi apparatus antibody. This serum recognized a 64 kD polypeptide in immunoblotting with HEp-2 cells. To verify that the 64 kD polypeptide was associated with the Golgi apparatus and to characterize which Golgi component was recognized, a monoclonal antibody was produced. IgG, isolated from this serum, was used in affinity chromatography to produce purified material which was used to generate a mouse monoclonal antibody. The monoclonal antibody had an indirect immunofluorescent pattern identical to that produced by the patient's serum, and similarly recognized a 64kD polypeptide in immunoblotting. A 59 kD polypeptide was also recognized by the monoclonal antibody, suggesting that the antigens recognized by the monoclonal and serum antibodies may be only partially identical. The antigen appears to be a glycoprotein and an integral component of the Golgi cisternae membranes. PMID- 1604249 TI - Lupus anticoagulant: interference with in vivo prostaglandin production and with platelet sensitivity to prostacyclin. AB - The hypothesis has been made that inhibition of prostacyclin (PG12) production may play a role in the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), but so far no evidence of reduced PG12 levels in vivo has been produced. We have tested the plasma levels of PG12 and thromboxane A2 (TXA2) and the platelet sensitivity to PG12 in 14 patients with and without LA and in 14 healthy controls. No significant difference in the prostanoid basal levels was detected among the groups; however, in some patients PG12 increments seemed to parallel the clinical course of the disease. Platelet sensitivity to exogenous PG12 was significantly enhanced in the LA + patients and correlated with PG12 values. We suggest that in these subjects additional factors, other than reduced PG12, may predispose to thrombosis. PMID- 1604250 TI - A five day course of high dose corticosteroids has no effect on the clearance of soluble aggregates of human immunoglobulin G in healthy volunteers. AB - It is thought that glucocorticosteroids impair the clearance of immune complexes by the mononuclear phagocyte system (MPS). We studied the effect of a five day course of prednisone (1 mg/kg body weight per day) on MPS function in 10 healthy volunteers, using soluble radiolabeled aggregates of human immunoglobulin G as a probe. MPS function was assessed before steroid treatment, and again 24 hours after the last dose of prednisone. Elimination kinetics and the uptake of the immunoglobulin aggregates by liver and spleen did not change after prednisone treatment. This suggests that, in contrast to general belief, high doses of glucocorticosteroids have no direct, acute effect on MPS function. PMID- 1604251 TI - Intravenous methylprednisolone pulse therapy in ankylosing spondylitis. AB - The aim of this double-blind study was to compare the effect of high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy administered intravenously once daily for three consecutive days, in active ankylosing spondylitis. Seventeen patients with active ankylosing spondylitis were randomly allocated to high-dose (8 patients) or low-dose (9 patients) regimen. Although there was no placebo group in this study, it is our impression that in patients with active ankylosing spondylitis, both high-dose (1000 mg) and low-dose (375 mg) methylprednisolone pulse therapy given on three consecutive days, is effective as regards pain relief and improvement in spinal mobility. There were no statistically significant differences between the two groups, though there was a trend towards the high dose yielding a greater and longer lasting improvement. No serious adverse reactions were observed. PMID- 1604252 TI - Low level laser therapy for myofascial pain in the neck and shoulder girdle. A double-blind, cross-over study. AB - In a controlled, cross-over study the effect of low level laser therapy (LLLT) was evaluated. During a five weeks period forty-seven female laboratory technicians received six laser and six placebo treatments to tender points in the neck and shoulder girdle. Subjects rated the placebo treatment significantly more beneficial than LLLT (p = .04). There was no reduction in consumption of analgesics associated with either laser or placebo treatment. The results indicate no beneficial effect of LLLT for myofascial pain. PMID- 1604253 TI - Predictors of mortality in non-post-operative patients with septic arthritis. PMID- 1604254 TI - Sensitivity of radiographic changes of hand and foot joints as a diagnostic criterion in patients with rheumatoid arthritis. PMID- 1604255 TI - Magnetic resonance imaging of the brain in patients with primary Sjogren's syndrome. PMID- 1604256 TI - The concomitant occurrence of Sjogren's syndrome and polymyositis. AB - A patient with both Sjogren's syndrome and polymyositis is described. The literature on the concomitant occurrence of these disorders is reviewed. PMID- 1604257 TI - The effect of shoulder muscle training in patients with recurrent shoulder dislocations. AB - Thirty-three shoulders in 29 patients with recurrent shoulder dislocations, of both traumatic and nontraumatic type, have been studied. The patients suffered from muscle weakness, and had also a hypotrophy of the supra- and infraspinatus muscles. A special training program using an isokinetic pulley-weight apparatus, for muscle strength, coordination and endurance training of the rotator-cuff muscles and the deltoid were given all patients. Shoulder flexors, internal and external rotator muscles were trained three times a week, during a period of 8 weeks. At follow-up one year after completion of the specific training program all shoulders except five were improved. Five shoulders had remaining instability. Four of these patients had generalized joint laxity and a much decreased humeral head retroversion, and were later on stabilized with a rotational osteotomy of the proximal humerus. One of the shoulders with remaining instability was of traumatic type with normal skeletal anatomy. This patient was later on stabilized with a Putti-Platt procedure. We conclude that most of the patients were relieved from pain, and had decrease or cessation of their dislocations. Factors indicating a less good result of training were an abnormal skeletal anatomy, and/or a multidirectional type of instability. PMID- 1604258 TI - A computerized wheelchair ergometer. Results of a comparison study. AB - To determine the validity of propulsion simulation on a stationary wheelchair ergometer, nine male able-bodied subjects performed submaximal exercise tests on the ergometer and on a motor driven treadmill (MDT). Oxygen uptake, ventilation and stroke parameters were equal for both devices, but heart rate was lower and trunk movement was less for the ergometer test. Analysis of forces and power output on the ergometer indicated that power output was equal for both wheels. The ratio between applied forces and the effectively directed force component was approximately 80%. Also a small torque was applied by the hand onto the handrim surface which contributed to the total propulsion torque around the axle. It is concluded that the ergometer is capable of simulation of wheelchair propulsion, although the different trunk motion may necessitate sufficient wheelchair propulsion experience. Force analysis results are discussed. PMID- 1604259 TI - Age related changes in surface myoelectric signals. AB - The initial values and the time course of muscle fiber conduction velocity and of surface myoelectric signal spectral variables were studied during voluntary or electrically elicited contractions of the tibialis anterior muscle of 15 healthy elderly human subjects. Age ranged from 65 to 84 years. Isometric voluntary contractions were performed at 20% MVC (Maximal Voluntary Contraction) and 80% MVC for 20 s. Tetanic electrical stimulation was then applied to the main muscle motor point for 20 s with surface electrodes. Two stimulation rates (20 Hz and 40 Hz) and two stimulation amplitudes were used to induce different degrees of fatigue. One stimulation amplitude was supramaximal, the second was adjusted to induce a response (M-wave) about 30% of the maximal. Results were compared with those reported in previous work on healthy adults (age range 18 to 43 years). The main findings of this work are: (a) when voluntary contraction level is increased from 20% MVC to 80% MVC conduction velocity and spectral variables increase; this increase is significantly smaller in elderly subjects, (b) during sustained contractions at 80% MVC the decrease of conduction velocity and spectral variables is significantly smaller in elderly subjects, (c) during contractions induced by supramaximal stimulation at 40 Hz the decrease of conduction velocity and spectral variables is not significantly different in the two age groups. It is concluded that points a and b reflect the age related decrease of number and size of fast twitch fibers indicated by histological data. Point c is discussed and possible explanations are suggested. PMID- 1604260 TI - Low level laser versus placebo in the treatment of tennis elbow. AB - The effect of low level laser (GaAs) on lateral epicondylitis was investigated in a double-blind, randomized, controlled study. Thirty patients were assigned equally to a laser (n = 15) or a placebo laser (n = 15) group. All patients received eight treatments and were evaluated subjectively and objectively before, at the end of, and four weeks after treatment. Patients also completed a follow up questionnaire on an average of five to six months after treatment. A significant improvement in the laser compared to the placebo group was found on visual analog scale (p = 0.02) and grip strength (p = 0.03) tests four weeks after treatment. In this study low level laser therapy was shown to have an effect over placebo; however, as a sole treatment for lateral epicondylitis it is of limited value. Further studies are needed to evaluate the reliability of our findings and to compare laser to other established treatment methods. PMID- 1604261 TI - Post-polio lung function. AB - Post-polio patients sometimes complain about the occurrence of breathing difficulties decades after the polio infection. We have examined 40 post-polio patients who have had respiratory or non-respiratory poliomyelitis for at least 30 years in an attempt to elucidate whether hypoventilation is common and to what extent certain symptoms and simple lung function tests are related to hypoventilation or incipient hypoventilation. We measured arterial blood gases, vital capacity (VC), maximal expiratory and inspiratory pressures (MEP, MIP) and CO2 rebreathing response. Symptoms were assessed by a yes/no questionnaire. Six patients required respiratory assistance at the onset of the disease. At present, two require nocturnal assisted ventilation. Two patients showed manifest hypoventilation; one of which required night-time ventilator, whereas the other patient had not required ventilatory assistance even at the onset of the disease. Significant correlation (p less than 0.05) was found between arterial carbon dioxide tension (a-PCO2) and VC, MEP and ventilation increase during CO2 rebreathing. A significantly higher a-PCO2 was found among those who required respiratory assistance at the onset of the disease, who admitted headache and who felt the cough ineffective. Low VC and low ventilatory increase during CO2 rebreathing and the presence of headache explained 45% of the variation in a-PCO2 in a multiple regression analysis. We conclude that manifest hypoventilation is rare in this unselected material of post-polio patients and that a vital capacity below 45-50% of predicted normal and the presence of frequent headaches indicate an increased risk to develop hypoventilation. PMID- 1604262 TI - Low energy high frequency pulsed electromagnetic therapy for acute whiplash injuries. A double blind randomized controlled study. AB - The standard treatment of acute whiplash injuries (soft collar and analgesia) is frequently unsuccessful. Pulsed electromagnetic therapy PEMT (as pulsed 27 MHz) has been shown to have pro-healing and anti-inflammatory effects. This study examines the effect of PEMT on the acute whiplash syndrome. One half of the 40 patients entering the study received active PEMT collars: the other half facsimile (placebo). All patients were given instructions to wear the collar for eight hours a day at home and advised to mobilise their necks. At 2 and 4 weeks the actively treated group had significantly improved (p less than 0.05) in terms of pain (visual analogue scale). By chance movement scores for the PEMT group were significantly worse at entry to the study than the control group (p less than 0.05). At 12 weeks they had become significantly better (p less than 0.05). PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury. PMID- 1604263 TI - Mucus clearance at rest and during exercise in patients with bronchial hypersecretion. AB - The purpose of this study was to measure the effects on mucus clearance after physical exercise. We measured mucociliary clearance at rest and during exercise in eleven patients with mild or moderate bronchial hypersecretion. The subjects inhaled an aerosol containing 99mTc-labelled albumin millimicrospheres. Four sets of scintigraphic images were obtained with 15 minute intervals. The lung retention of radioactivity was quantified using a gamma camera and the clearance of particles from the lungs were calculated for each 15 min period. The first image was obtained directly after inhalation, the second after a period of 15 min rest, the third after a period of exercise on a bicycle ergometer and the final fourth image after another period of rest. We found no differences in the clearance rate at rest and after exercise. PMID- 1604264 TI - Body weight-bearing while rising and sitting down in patients with stroke. AB - Distribution of body weight on the two legs while rising and sitting down was examined in 42 subacute stroke patients and 16 healthy adults during both spontaneous movement and following instruction directed at even weight distribution. Vertical floor reaction forces were measured by two force plates. There was a difference between patients and controls in the tested motor tasks- the patients favoured their nonparetic leg. However, body weight distribution was less asymmetric when patients tried to rise and sit down evenly compared to spontaneous rising/sitting down (p less than 0.001). Patients' own estimation of distribution of body weight documented on a visual analogue scale, correlated with actual body weight distribution while rising (rs = 0.36) but not while sitting down. To motivate stroke patients to pay attention to their ability to distribute body weight evenly while rising and sitting down and to create and use adequate self-reports seems a necessary commitment in a rehabilitation programme in order to avoid the learned nonuse syndrome. PMID- 1604265 TI - Diagnostic blocks of the tibial nerve in spastic hemiparesis. Effects on clinical, electrophysiological and gait parameters. AB - The value of a diagnostic block (DB) of the tibial nerve in 17 hemiparetic patients with gait disturbances was investigated. The purpose of this study was to find instruments that help to select patients who will benefit from a long lasting peripheral nerve block. The manually elicited ankle clonus and its abolition after injection of a local anaesthetic appeared to be a useful clinical test for the efficacy of DB. Electrophysiological tests proved valuable when DB failed to produce clinical effects. With a substantial number of blocked nerve fibres walking velocity did not deteriorate. Transient disturbances in sensation can be regarded as unwanted side effects that might adversely affect the walking ability. From the different aspects of gait an improved heelcontact demonstrated the functional gain in patients with a dynamic equinus foot. To differentiate between a dynamic equinus foot and fixed contractures, we recommend the use of a fast acting local anaesthetic for diagnostic nerve blocks. PMID- 1604266 TI - Postural reorganization following lower limb amputation. Possible motor and sensory determinants of recovery. AB - Postural control was assessed in persons with a unilateral lower limb amputation before and after their rehabilitation. The centre-of-pressure fluctuations during quiet upright standing on a dual-plate force platform were registered with and without visual information in order to identify relevant determinants of balance restoration. In addition, static (weight distribution) as well as dynamic (control activity) asymmetry characteristics were examined. Besides a small improvement in balance control with full visual information (fore-aft sway, p less than 0.06; lateral sway, p less than 0.05), there was a major decrease in visual dependency (fore-aft and lateral sway, p less than 0.05) indicating a somatosensory re-integration process. Postural asymmetry in comparison with matched control subjects was most apparent and only significant in dynamic terms and remained constant across rehabilitation. It is concluded that after a lower limb amputation a central reorganization of postural control takes place, in which sensory determinants of motor recovery may play a critical role. PMID- 1604267 TI - Muscle training in chronic anterior cruciate ligament insufficiency--a comparative study. AB - The aim of the investigation was to study and compare the effect of two basically different training methods on muscle strength and knee function on a consecutive and prospective series of 26 conservatively treated patients with chronic anterior cruciate ligament injury. The two training models were: model Q directed towards specific training of knee extensor muscle strength and model F aiming at training of the lower extremity and trunk muscles in functional weightbearing patterns. The parameters evaluated were: isometric and isokinetic muscle strength, a performance test (one-leg hop test), and a functional score. The results after a three-month training period showed in both groups a significant increase of muscle strength in both knee extensors and knee flexors. No significant difference of isokinetic strength values between the two groups was observed. The isometric gain of knee extension was significantly higher in the Q group. The one-leg hop test value and the functional score were also significantly increased in both groups. However, the hop test indicated a more favourable result in the group who were trained functionally. PMID- 1604268 TI - Algometry. Measuring pain threshold, method and characteristics in healthy subjects. AB - A pressure algometer was tested using a specially designed protocol in 28 healthy adult males and females. Two observers examined the pressure threshold (PT) of local tenderness at the joints of the wrists, elbows, knees, ankles, and at the paravertebral tissues. Several characteristics of the instrument were found. There were no significant differences in PT's between the same points on either side of the body (r = 0.738-0.934). A large source of variance was the measurement of one area within short time intervals. No significant differences in means were found between the two observers for the paravertebral points, while significant differences were found at the peripheral joints. Male subjects had significantly higher PT's than females. The PT's of the paravertebral tissues decreased in a cranial direction, while PT's of the peripheral joints showed similar levels. There was no significant influence on observing PT's on different dates or in a different order. PMID- 1604269 TI - Effect of occupational exposure to cobalt blue dyes on the thyroid volume and function of female plate painters. AB - It has previously been shown that long-term oral exposure to cobalt can cause goiter and myxedema. The effect of industrial cobalt exposure on thyroid volume and function was determined for 61 female plate painters exposed to cobalt blue dyes in two Danish porcelain factories and 48 unexposed referents. Thyroid volume was determined by ultrasonography. The cobalt blue dyes were used in one of two forms, cobalt aluminate (insoluble) and cobalt-zinc silicate (semisoluble). Only the subjects exposed to semisoluble cobalt had a significantly increased urinary cobalt content (1.17 micrograms.mmol-1 versus 0.13 micrograms.mmol-1, P less than 0.0001). These subjects also had increased levels of serum thyroxine (T4) and free thyroxine (FT4I) (P = 0.0001 and 0.0029, respectively), unaltered serum thyroid stimulating hormone (TSH), and marginally reduced 3,5,3'-triiodothyronine (T3), whereas thyroid volume tended to be lower (P = 0.14). The group exposed to insoluble cobalt did not differ significantly in any thyroid-related parameters. No correlation between urinary cobalt and FT4I or thyroid volume was found. The study demonstrates an effect of cobalt on thyroid hormone metabolism. PMID- 1604270 TI - Magnitude of misclassification bias when using a job-exposure matrix. AB - A job-exposure matrix constructed in Southampton, the United Kingdom, was assessed with the use of 1205 occupational histories collected for a case referent study on primary liver cancer in Finland. The odds ratios calculated on the basis of the matrix and an assessment by occupational hygienists were compared. The ability of the matrix to detect excess risk was generally satisfactory for chemical and physical agents to which about 10% or more of the studied population was exposed. If only probable exposure at a high level was assigned to the category of the exposed, an excess risk was usually detectable also when the prevalence of exposure was below 10%. This assessment indicates that the British job-exposure matrix is an acceptably valid screening tool also outside the United Kingdom, provided that the misclassification characteristics of the matrix and the significant differences in exposure between the countries are taken into account. PMID- 1604271 TI - Chelated lead and bone lead. AB - In this study a close correlation [correlation coefficient (r) = 0.86, P less than 0.001] was found between the blood lead level of 20 lead workers and their urinary excretion of lead for 24 h after intravenous infusion with 1 g of the chelating agent calcium disodium edetate. In addition, there were significant associations between lead levels in different bones (tibia/calcaneus: r = 0.93, P less than 0.001; tibia/phalanx: r = 0.67, P less than 0.002; calcaneus/phalanx: r = 0.80, P less than 0.001), as measured by in vivo X-ray fluorescence. Chelation produced no significant change in the lead level in either tibia or calcaneus. There was a significant correlation between chelated lead and bone lead (eg, for calcaneus, r = 0.62) in currently exposed workers. However, there was no significant relationship when a retired worker and an inactive worker were included (r = 0.14). It was concluded that chelatable lead mainly reflects the blood and soft-tissue lead pool, which is only partly dependent upon the skeletal lead content that comprises the biggest share of the total body burden. PMID- 1604272 TI - Carcinogens in rubber production in the Soviet Union. AB - In a preliminary phase of a broad research project on cancer among workers in a rubber footwear plant in Moscow, exposure to several known or potential carcinogens was assessed. There were high dust contents bearing both toxic substances and carcinogens. The highest concentrations of benzo[a]pyrene (500 14,400 micrograms) were found on the soot used as a filler, and the maximum N dimethylnitrosamine (DMNA) level was measured in thiram (150-23,868 micrograms.kg 1). Air samples from the vulcanization process and the pressing of rubber goods showed BaP levels of up to 1.43 micrograms.m-3. In the work area where polyvinyl chloride was used, the mean vinyl chloride concentration was 0.21 (SE 0.06) mg.m 3. The mean value of the acrylonitrile concentrations in the workroom area was 0.19 (SE 0.07) mg.m-3. Very high levels of DMNA and N-diethylnitrosamine were measured in the preparatory shop in the winter. PMID- 1604273 TI - Sympathetic nerve activity in the skin in relation to vibration-induced white finger. AB - With a microneurographic method, sympathetic nerve activity in the skin was recorded from median nerve fascicles of six patients with vibration-induced white finger and four age- and gender-matched normal subjects. At an ambient temperature of 15 degrees C the sympathetic nerve activity was greater in the patients than in the normal subjects. The burst activity was increased in all of the subjects during the water immersion test of the contralateral hand, but neither the increase in the mean burst number nor the mean area under the neurogram showed statistically significant group differences. Thus, although vasoconstrictive tone is greater in patients with vibration-induced white finger than in healthy subjects, no support could be found for the hypothesis that increased vascular tone is of prime importance for attacks of white finger in vibration-exposed subjects. PMID- 1604274 TI - Antibodies against Yersinia among farmers and slaughterhouse workers. AB - Antibodies to immunoglobulins (Ig) M, G, and A against Yersinia enterocolitica serotypes O:3, O:5, O:8, and O:9 and Yersinia pseudotuberculosis serotypes I and III were analyzed by enzyme immunoassay of the serum samples of 161 slaughterhouse workers, 147 pig farmers, and 114 grain or berry farmers. The crude risk ratios for elevated serum antibody concentrations were calculated with the use of the grain and berry farmers as the reference population. The risk for an elevated Y enterocolitica O:3 Ig G concentration was 3.0 (95% confidence interval (95% CI) 1.3-7.1) for the pig farmers and 1.8 (95% CI 0.7-4.4) for the slaughterhouse workers and the respective risks for elevated Y enterocolitica O:9 Ig G were 2.4 (95% CI 1.1-5.5) and 1.7 (95% CI 0.7-4.0). Since these two serotypes are commonly associated with swine, the increased number of subjects with elevated antibody levels could be causally related to occupational contact with this animal. PMID- 1604275 TI - Cancer mortality and incidence in mastic asphalt workers. PMID- 1604276 TI - Relationship of ergonomic stressors to birthweight and gestational age. AB - Women in many occupations are exposed to ergonomic stressors (eg, prolonged standing, physical exertion, and long work weeks). After a consideration of the major methodological problems encountered in studying effects of ergonomic stressors on birthweight and gestational age, epidemiologic studies that have addressed this issue are reviewed. No individual ergonomic stressor has been consistently associated with effects on gestational age. However, most studies which have attempted to look at the cumulative effect of several stressors report that women in the highest exposure category are at higher risk of giving birth prematurely. In contrast, data regarding an association with birthweight are more variable, and firm conclusions cannot be drawn. While future studies that assess exposure to ergonomic stressors with a more comprehensive and quantitative approach are needed, current evidence is sufficient to suggest that clinicians should take ergonomic stressors into account in the assessment of their patients' risk for preterm delivery. PMID- 1604277 TI - Cluster of brain cancers spuriously suggesting occupational risk among glassworkers. AB - Indications of an increased risk of brain cancer in some, but not all, epidemiologic studies on glassworkers inspired further investigations in a geographically restricted region where the Swedish glass industry is located. Only a small and insignificant excess of brain cancer death was found among glassworkers when compared with the rest of the population in the area. However, when the brain cancer mortality of the glassworkers was compared with that of the whole Swedish population, a rather high risk was found, but an equally high risk was also seen for the rest of the population in this region when compared with national figures. Besides glassworkers, especially farmers, but also other occupational groups had an increased risk of brain cancer that suggested the possibility of an environmental factor affecting the whole population in the region. Hence particular worker groups may sometimes take on a regional mortality pattern that simulates an occupational risk. PMID- 1604278 TI - Mortality study of ethanol and isopropanol production workers at two facilities. AB - The mortality experience of alcohol process workers (N = 1031) from two chemical plants was followed from the early 1940s to 1983. Reported associations of the production of ethanol and isopropanol by the strong-acid process with upper respiratory tract cancers, heart disease, and lympho- and reticulosarcoma were tested with both external and internal comparisons. Excesses of cancers of the larynx, buccal cavity, and pharynx, based on very small numbers, were observed. There was one death due to sinus cancer. It could not be concluded that there were work-related effects on mortality due to heart disease or lympho- or reticulosarcoma. Workers assigned to the production of isopropanol by the weak acid method showed no evidence of excess cancer mortality (0 observed, 1.9 expected cancer deaths). The absence of major risks among strong-acid workers can be explained by the initiation of engineering controls and health monitoring that took place after the original medical observations. PMID- 1604279 TI - Does long-term concrete work cause silicosis? AB - The machining of cast concrete often produces heavy exposure to respirable silica dust. Work with concrete in general results in considerably less exposure, however, and only a few cases of silicosis due to work with concrete have been reported. Telephone interviews with detailed questions on occupational history were made with 271 construction workers specializing in concrete work for more than 20 years, and exposure data were evaluated for different work tasks. The mean cumulative exposure of subjects to silica was estimated to be 2.4 mg.years.m 3. Chest radiographs were classified according to the International Labour Office classification. There was no suspicion of silicosis for any of the workers. The risk of contracting silicosis from work with concrete in the Swedish construction industry in recent decades is considered to be slight and does not justify general, periodic chest radiographic screening. PMID- 1604280 TI - Stress failure of pulmonary capillaries in the intensive care setting. AB - Recent work shows that when the pressure in pulmonary capillaries is raised to high levels, ultrastructural changes occur in their walls including disruption of the capillary endothelium, alveolar epithelium, or sometimes all layers. Since the calculated wall stresses are extremely high, this condition is referred to as stress failure, and it results in a high permeability type of pulmonary edema, or even frank hemorrhage. Stress failure is believed to play a part in diseases where the capillary pressure is abnormally high, such as neurogenic pulmonary edema, high altitude pulmonary edema, exercise-induced pulmonary hemorrhage in racehorses, and perhaps some cases of the adult respiratory distress syndrome. Stress failure also occurs if the blood-gas barrier is weakened as in Goodpasture's syndrome. Another important cause is overinflation of the lung as may occur with mechanical ventilation and high inflation pressures. Stress failure of pulmonary capillaries is a hitherto overlooked and potentially important factor in the intensive care setting. PMID- 1604281 TI - [Sepsis: confusion of terms]. AB - Recent developments in the pathophysiology and treatment of sepsis have clearly shown the confusion produced by the imprecise terminology used to define the various facets of the sepsis process. The criteria required to diagnose bacteremia, sepsis, sepsis syndrome or septic shock vary from one author to the other. This inaccuracy accounts for the inability to compare the results of therapeutic investigation from different groups. The aim of this article is to point out the necessity of standardized terminology and to propose definitions which might be appropriate. PMID- 1604282 TI - [Septic syndrome: cardiocirculatory assessment]. AB - Severe sepsis is characterized by increased oxygen demand, alteration of oxygen extraction, and a diminution of myocardial contractility. The importance of each of these three factors is directly related to the severity of the sepsis. The combination of these factors may lead to tissue hypoxia, which is the shortest route to development of multiple organ failure (MOF). The presence of tissue hypoxia should be suspected in the presence of lactic acidosis. The phenomenon of dependence on oxygen consumption (VO2) in relation to oxygen transport (DO2) is detectable where there is a rise in DO2 induced by perfusion of liquids or administration of vasoactive agents. Study of the relationship between cardiac flow and oxygen extraction is a simple means of studying the relations between VO2 and DO2 at the patient's bedside. PMID- 1604283 TI - [Sepsis syndrome: progress and therapeutic perspectives]. AB - To reduce the very high mortality rate due to septic shock, a new clinical entity has been defined: sepsis syndrome. The aggressive treatment of any sepsis syndrome should prevent the evolution towards a state of shock and thus reduce the risk of a fatal outcome. It consists in broad spectrum antibiotic therapy associated with hemodynamic support (volume resuscitation, vasopressors and inotropic agents) at the first signs of cardiocirculatory failure. Several pharmacological or immunological interventions--antagonists directed at mediators and multiple cytokines involved in the pathogenesis and perpetuation of sepsis syndrome and septic shock--have been successful experimentally. However, new therapies, such as those using monoclonal antibodies against endotoxins of TNF, cannot yet be considered established. PMID- 1604284 TI - Oxygen transport in septic shock. AB - Septic shock is an acute impairment of tissue perfusion, characterized by hypotension, low systemic vascular resistance and increased blood levels of lactate. Myocardial dysfunction is common despite hyperdynamic circulation, and may limit the patient's ability to respond to increased tissue oxygen demand. The treatment of hypotension necessitates the use of sympathomimetic drugs, which may compromise regional tissue perfusion despite overall stabilization of hemodynamics. The disproportionately high splanchnic oxygen demand in sepsis makes the splanchnic region susceptible to tissue hypoxia, which may contribute to the development of multiple organ failure in septic shock. Since the changes in regional oxygen transport do not necessarily parallel changes in systemic oxygen transport, the effects of vasoactive drugs on regional blood flow in sepsis should be studied in more detail. PMID- 1604285 TI - [Pathogenetic and clinical significance of peripheral activated T-lymphocyte subsets in Basedow's disease]. AB - The peripheral activated T-cell subsets which express concurrently DR and CD antigens were determined in 22 patients with Graves' disease using the fluorescence-rosette double labelling technique. In the active phase of the disease a decrease in the percentage of CD8+ cells, an increase in the CD4+/CD8+ ratio and an elevation of various DR+CD+T-lymphocytes was found. A concurrent marked increase in DR+CD4+ cells accounts for an abnormality in the equilibrium of activated T-lymphocyte subsets and an increase in DR+CD4+/DR+CD8+ ratios. In comparison with the active phase the DR+CD3+ and DR+CD4+ cells decreased in remission, but DR+CD8+ cells remained unchanged. The decrease in the ratio of CD4+/CD8+ cells was less marked than that of the DR+CD4+/DR+CD8+ cells, which fell into the normal range. Our results suggest an excessive activation of T helper cells as well as a deficiency in T-suppressor cells which may play an important role in the pathogenesis of Graves' disease. PMID- 1604286 TI - [Effect of halving the dosage of atenolol in essential hypertension]. AB - In the present study the effect of halving the dose of atenolol in 41 essential hypertensives was analyzed. Prereduction dosage of atenolol was 100 mg in 26 and 50 mg in 15 patients. In 16 cases the beta-blocker was administered as monotherapy and in the remaining patients atenolol was combined with a calcium antagonist and/or a diuretic. Dosage of these drugs was constant throughout the whole study. During an observation period of 12 weeks after halving atenolol from a mean dose of 82 mg to 41 mg, no significant changes in systolic and diastolic blood pressure or in response rate (defined as a diastolic blood pressure of 95 mm Hg or less) were observed. In view of our results and those of other authors, it is recommended that in patients with mild hypertension whose blood pressure has been kept below 140/85 mm Hg by treatment for at least one year, betablockers may be reduced in a step-wise fashion. PMID- 1604288 TI - [Functional gait disorders]. AB - The spectrum of hysterical or functional gait disorders in 47 patients is discussed. Some patients experience a single episode or a transient monoparesis of one leg, but there are patients who are left with a chronic paraplegia. To characterize neurological symptoms for which no organic origin can be demonstrated, we prefer the term "functional". The reasons for using this term are discussed. PMID- 1604287 TI - [Acute fatty liver of pregnancy--differential diagnosis and supportive therapy]. AB - A case of clinically diagnosed acute fatty liver of pregnancy (AFLP) is reported. Hypoglycemia and coagulopathy were predominant in the clinical course. Serial studies on blood chemistry, especially blood glucose and coagulation parameters, in association with virus serology and ultrasound, can rule out common causes of jaundice in pregnancy. This contributes to reliability of the clinical diagnosis of AFLP in the absence of liver biopsy, and ensures adequate management of the patient. PMID- 1604289 TI - [Arthropathy due to hemochromatosis: often inaugural manifestation of the disease]. AB - Idiopathic hemochromatosis is a recessive autosomal disorder of iron metabolism manifested by a tissue overload affecting many organs, including the liver, the heart, the endocrine glands and the joints. Of 53 patients we studied, 66% had articular symptoms (mainly arthralgias of the metacarpophalangeal joints) and 49% had radiological lesions such as chondrocalcinosis and structural joint damage. The radiological signs were slightly more frequent in women (56.3%) than men (45.9%). Mean age at diagnosis was moderately higher in the group with arthropathy (52 years) than in the group without (44 years). Analysis of clinical, radiological and biological data, including parathormone values, did not reveal other parameters differentiating the two groups. A family study does not support the hypothesis of double heredity for hemochromatosis and arthropathy. In 20% of the patients the arthropathy was the inaugural feature of the hemochromatosis. The interval between first symptoms and diagnosis for these patients (5.3 years on average) is unfortunately long. Determination of transferrin saturation allows early diagnosis. PMID- 1604290 TI - [Endoscopic Doppler ultrasonography in lower intestinal bleeding:vascular diagnosis and monitoring of therapy]. AB - Endoscopic Doppler sonography is a relatively new method for evaluating the sources of intestinal bleeding. For the most part our experiences derived from cases of gastroduodenal ulcer bleedings, in which Doppler sonography permits the identification of arterial vessels relevant for recurrent ulcer bleedings as well as follow-up of therapy after sclerosing. In the lower intestinal tract endoscopic Doppler has, however, only rarely been used, e.g. for diagnosing vascular malformations. This method is of theoretical interest for evaluating colorectal sources of bleeding but is nonetheless of some practical importance, as our investigations of angiodysplasias, ulcers of the rectum and polyps demonstrate. PMID- 1604291 TI - [Secondary oxalosis following small bowel resection with kidney insufficiency and oxalate vasculopathy]. AB - A 58-year-old female patient admitted to hospital for advanced renal failure had a 40 years' history of Crohn's disease and had undergone ileocecal resection. Nevertheless, chronic diarrhea persisted. Subsequently calcium oxalate stones in the urine were repeatedly observed. Progressive renal failure developed. The investigation of the patient showed severe steatorrhea and pronounced hyperoxaluria, and renal biopsy showed severe chronic interstitial nephritis with calcium oxalate crystals. The skin biopsy revealed severe calcium oxalate vasculitis. The pathophysiology and therapy of secondary hyperoxaluria due to small bowel resection are discussed. PMID- 1604292 TI - [Bicavitary cardiac stimulation. Re-assessment and results]. AB - In each indication for cardiac stimulation, dual chamber pacing must be considered if stimulation or sensing in the atrium is possible. It is of particular importance in patients with diastolic ventricular dysfunction. The Heart rate is the most important parameter in stress-adaptation; for this reason we propose to use exclusively the VVIR or DDDR stimulation mode in physically active patients. Complications of dual chamber pacing are rare. During follow-up it is important to limit the energy of impulses and so to enhance the longevity of the generator, and to verify other parameters such as adaptation of the rate adaptation sensor and the AV delay intervals for sensed and paced atrial events. Modern technology allows us to reach the two most important goals of cardiac stimulation: avoid syncopes due to excessive bradycardia or asystole and optimize the quality of life of our patients. PMID- 1604293 TI - [Aneurysma spurium following arterial catheterization: diagnosis and follow-up]. AB - Pseudoaneurysm (PA) formation is one possible complication after intra-arterial catheterisation. Due to danger of rupture PA must be clearly differentiated from haematoma. PA is an arterially perfused cavity near the puncture site with direct communication with the femoral artery. Its clinical diagnosis is unreliable. We systematically reviewed 628 patients who had undergone femoral catheterisation (for angiography, PTA, local thrombolysis or aspiration) over a period of 1 year. Duplex scanning was performed within 1 to 3 days after puncture in the cases with the slightest suspicion of PA. In 7 patients (1.1%) PA could be confirmed (2 after angiography, 3 after PTA and 2 after local lysis). On the ultrasound B-mode image PA appears as a low or anechoic structure which can be precisely measured. With pulsed (colour) Doppler, flow can be detected within a PA, allowing easy differentiation from thrombosed PA or from haematoma. The velocity of the systolic inflow-jet as well as of the diastolic outflow can be determined. The velocity of the inflow-jet will usually be much higher than the blood flow velocity in the femoral artery. Duplex-scanning allows repeated non-invasive follow-up examinations for better determination of indications for surgery. Of the 7 diagnosed PA, 2 needed prompt operation (1 because of rupture, 1 because of intense local pain). One patient required operation during follow-up because of increase in size of PA. In the remaining 4 patients, spontaneous thrombosis was observed with repeated duplex examinations. PMID- 1604295 TI - [Saphenous vein bypass stenoses, early diagnosis with color coded Doppler sonography]. AB - In a prospective study 54 patients with 62 saphenous vein arterial bypass grafts were examined by colour-coded Doppler sonography and angiography. Five cases of graft occlusion were diagnosed by colour-coded Doppler sonography and confirmed by angiography. In comparison with angiography, colour-coded Doppler sonography showed a sensitivity of 92% and a specificity of 100% in the detection of focal graft stenosis. Only two stenoses in the region of the distal anastomosis could not be detected by colour-coded Doppler sonography. In 28 cases a marked dilatation of the proximal anastomosis was found corresponding to the surgically used patch angioplasty. Within this dilated bypass segment, turbulence and flow reversal zones were demonstrated, which might be predisposing factors for graft stenosis. Colour-coded Doppler sonography can accurately detect saphenous vein arterial bypass graft stenoses and should be routinely used in postoperative screening. PMID- 1604294 TI - [Color coded Doppler sonography of the vertebral arteries. Comparison with conventional duplex sonography]. AB - In 60 patients the vertebral arteries were investigated to determine whether color Doppler imaging has advantages over conventional duplex ultrasonography. The vertebral artery was easily identified in the midcervical course (V1-V2 segment) with both methods. Visualization at the atlas loop (V3 segment) was rarely successful with duplex scanning, however, color Doppler imaging enabled good documentation of vertebral artery flow in 87% on the right and in 85% on the left side. Color Doppler imaging provided better evaluation of the vertebral origin (V0 segment). Although visualization of the ostium with duplex scanning was more difficult and time consuming, it was possible in 80% on the right and in 65% on the left side. Color Doppler imaging allowed more rapid identification of the origin in 88% on the right and in 73% on the left side. The special problems of visualization of vertebral arteries with both methods and characteristic color coded Doppler sonographic features of pathological findings are discussed. PMID- 1604296 TI - [Instruments and treatment principle of ultrasound osteotomy in mouth, jaw and facial surgery]. AB - Ultrasonic instruments, technical principles and characteristics of ultrasonic osteotomy are presented. The clinical value is assessed. A software for 3D reconstruction of tomographic pictures on personal computers is used for better planning of surgical operations. PMID- 1604297 TI - [A Doppler ultrasound device for determining blood volume flow]. AB - A novel ultrasonic quantitative Doppler procedure has been developed which allows for the measurement of real-time volume flow in large blood vessels. It makes use of a 2D array transducer, which enables parallel sampling of a measuring slice placed in normal position to the sound beam. With this arrangement, volume flow can be computed without measuring the angle of incidence. Moreover, the 2D velocity distribution can be assessed within intervals of 10 to 30 ms. PMID- 1604298 TI - [Hormonal and ultrasound monitoring of early pregnancy--differential diagnosis of extrauterine pregnancy and multiple pregnancy]. AB - In this study sonographical and hormonal findings in 63 patients with intrauterine singleton pregnancy were compared with 18 patients with multiple pregnancies and 28 patients with ectopic pregnancy. The earliest detection of the intrauterine gestational sac was obtained with a HCG level of 659 mlU/ml. The sonographical development correlated well with HCG values. There was no statistically significant correlation between gestational age and HCG. In multiple pregnancies with sonographical findings comparable to the development in singletons HCG values were remarkably elevated. A discrimination between multiple and ectopic pregnancies by sonographical and hormonal criteria cannot be performed sufficiently in a HCG zone of 1500 mlU/ml. Close sonographical and hormonal follow-up until diagnosis of the intrauterine pregnancy is necessary. PMID- 1604299 TI - [Radiation sparing assessment of a child]. AB - In a seven-year old girl who had swallowed a big coin, the position of the foreign body in the stomach was demonstrated sonographically by means of the technique of the fluid filled stomach. Endoscopic removal after 48 hours was arranged without x-ray examination. PMID- 1604300 TI - [Potentials dangers in the diagnostic use of ultrasound]. PMID- 1604301 TI - Stress echocardiography. AB - Stress echocardiography is a relatively new imaging modality that is rapidly becoming the preferred technique to evaluate patients for and with coronary artery disease. This article will review how the procedure is performed, its diagnostic accuracy, its clinical role, and its advantages and disadvantages as compared to other imaging modalities. PMID- 1604302 TI - Freedom of choice in medicine--"it makes me feel better". PMID- 1604303 TI - Neuropsychiatric manifestations of vitamin B12 deficiency in the absence of anemia or macrocytosis: a case report. AB - We describe an atypical case of a young adult who had the acute onset of neuropsychiatric symptoms consistent with vitamin B12 deficiency despite a normal hematocrit, a normal MCV, a normal peripheral blood smear, a normal bone marrow biopsy, a normal Schilling test but abnormally low serum vitamin B12 levels. The patient responded quickly to parenteral vitamin B12 therapy but had mild residual symptoms at the time of his last clinic visit. PMID- 1604304 TI - Radiocesium in muscle tissue of reindeer and pike from northern Sweden before and after the Chernobyl accident. A retrospective study on tissue samples from the Swedish Environmental Specimen Bank. AB - After the Chernobyl accident in April 1986, considerable deposition of radionuclides occurred regionally in eastern, central and northwestern Sweden. Locally, the fallout of radiocesium exceeded the remainder from atmospheric nuclear weapons tests by several magnitudes. Since the end of the 1960s samples of organs from various plant and animal species, annually collected at different localities, have been preserved in the Swedish Environmental Specimen Bank (ESB). In this work samples from the ESB have been used for retrospective studies of radioactive pollution. The activities of Cs-134 and Cs-137 in muscle tissues from reindeer, Rangifer tarandus, and pike, Esox lucius, preserved in the ESB, were measured. The samples were collected annually; the reindeer at three localities in northern Sweden and the pike at one of them. In material collected prior to the Chernobyl accident, the levels of Cs-137 were 57-180 Bq/kg in reindeer and 14 24 Bq/kg in pike, fresh weight basis. These levels relate to earlier nuclear bomb tests. A significant decrease was found in pike during the pre-Chernobyl period (1971-86). In post-Chernobyl samples the burden of Cs-137 varied from amounts equal to the former levels in the northernmost locality and up to 80 times higher for the maximum values in the southernmost locality. The highest value recorded was 18,425 Bq/kg in reindeer. The geographic variations in reindeer from Chernobyl fallout were in accordance with the pattern of deposition estimated by aircraft surveys performed in May 1986. The ratio between 'new' and 'old' radiocesium burdens in pike, caught in 1987, approached the corresponding ratio for reindeer grazing in the precipitation area of the lake; 33 and 19, respectively. PMID- 1604305 TI - Vanadium levels in hair and blood of normal and exposed persons. AB - Vanadium was determined by both instrumental neutron activation analysis (INAA) and NAA with radiochemical separation (RNAA) in hair of normal children and of children potentially exposed by accidental drinking of vanadium contaminated water (long-term, low-dose exposure). Vanadium hair levels in the two groups did not differ significantly and were in the range 46-313 micrograms/kg (median 98 micrograms/kg) and 24-235 micrograms/kg (median 88 micrograms/kg for the normal and exposed groups, respectively. Using RNAA with proven reliability at the ultratrace level, vanadium was determined in whole blood of the exposed and normal children, normal adults and workers professionally exposed to vanadium in a factory producing vanadium pentoxide. Significantly increased vanadium concentrations were found in blood of exposed children (range 0.018-0.239 micrograms/l, median 0.078 micrograms/l) compared to normal children (range 0.024 0.226 micrograms/l, median 0.042 micrograms/l), while no differences could be detected between blood vanadium levels of normal children and normal adults (range 0.032-0.095 micrograms/l, median 0.056 micrograms/l). Preliminary results for vanadium in blood of occupationally highly exposed persons showed values 2-4 orders of magnitude higher than in normal adults. PMID- 1604306 TI - Contributions of risk factors to elevated blood and dentine lead levels in preschool children. AB - The relationship between blood lead level (PbB) and an array of socio demographic, behavioral, caregiving and environmental risk factors was investigated in a cohort of socioeconomically disadvantaged urban children at ages 2, 3 and 4 years and 10 months. The risk factors were also related to dentine lead level (PbD) from shed deciduous teeth. Strong persistent pairwise relationships with PbB and PbD were observed for maternal IQ, parental education, examiner ratings of the condition and cleanliness of the physical environment, and the HOME scale, which assesses the quality of the caretaking environment. The association between dirt pica and PbB was strong at 2 years (r = 0.30), but was less pronounced in subsequent assessments as the prevalence of pica decreased. Insignificant or weak relationships were found for maternal assessments of paint and-plaster peeling in the home and non-dirt pica. The HOME scale and the ratings of the condition of the physical environment were significantly related to PbB and PbD even after adjustment for socio-demographic factors. These two measures were also strongly related to an array of developmental outcomes. The results indicate that statistical adjustment specifically for the quality of the caretaking environment can lead to substantial reductions in estimates of adverse lead effects. PMID- 1604307 TI - Economic impact report. PMID- 1604308 TI - NIH leaks. PMID- 1604309 TI - Furor at Lyme disease conference. PMID- 1604310 TI - Errant HIV strain renders test virus stock useless. PMID- 1604311 TI - Panel clears Needleman of misconduct. PMID- 1604312 TI - Gallo wins one--and loses one. PMID- 1604313 TI - On the other hand... PMID- 1604314 TI - Human organ transplantation: background and consequences. AB - The story of the renal transplant program of the Peter Bent Brigham Hospital (now the Brigham and Women's Hospital) in Boston weaves together three distinct threads: the study of renal disease, the phenomenon of skin grafting in twins, and the development of surgical procedures ultimately leading to the use of chemical immunosuppression. The common leitmotiv is one of a single event or report proving to be decisive. Unanticipated consequences of successful human organ transplantation include the reorganization of clinical and nonclinical disciplines, national and international cooperation in organ preservation and distribution, tissue-typing as a marker for disease, redefinition of death in terms of brain function, better understanding of disease processes, and new health care quandaries that result from the scarcity of organ donors. PMID- 1604315 TI - Unusual resistance of peptidyl transferase to protein extraction procedures. AB - Peptidyl transferase, the ribosomal activity responsible for catalysis of peptide bond formation, is resistant to vigorous procedures that are conventionally employed to remove proteins from protein-nucleic acid complexes. When the "fragment reaction" was used as a model assay for peptide bond formation, Escherichia coli ribosomes or 50S subunits retained 20 to 40 percent activity after extensive treatment with proteinase K and SDS, but lost activity after extraction with phenol or exposure to EDTA. Ribosomes from the thermophilic eubacterium Thermus aquaticus remained more than 80 percent active after treatment with proteinase K and SDS, which was followed by vigorous extraction with phenol. This activity is attributable to peptidyl transferase, as judged by specific inhibition by the peptidyl transferase-specific antibiotics chloramphenicol and carbomycin. In contrast, activity is abolished by treatment with ribonuclease T1. These findings support the possibility that 23S ribosomal RNA participates in the peptidyl transferase function. PMID- 1604316 TI - Aminoacyl esterase activity of the Tetrahymena ribozyme. AB - Several classes of ribozymes (catalytic RNA's) catalyze reactions at phosphorus centers, but apparently no reaction at a carbon center has been demonstrated. The active site of the Tetrahymena ribozyme was engineered to bind an oligonucleotide derived from the 3' end of N-formyl-methionyl-tRNA(fMet). This ribozyme catalyzes the hydrolysis of the aminoacyl ester bond to a modest extent, 5 to 15 times greater than the uncatalyzed rate. Catalysis involves binding of the oligonucleotide to the internal guide sequence of the ribozyme and requires Mg2+ and sequence elements of the catalytic core. The ability of RNA to catalyze reactions with aminoacyl esters expands the catalytic versatility of RNA and suggests that the first aminoacyl tRNA synthetase could have been an RNA molecule. PMID- 1604317 TI - Sexually antagonistic genes: experimental evidence. AB - When selection differs between the sexes, a mutation beneficial to one sex may be harmful to the other (sexually antagonistic). Because the sexes share a common gene pool, selection in one sex can interfere with the other's adaptive evolution. Theory predicts that sexually antagonistic mutations should accumulate in tight linkage with a new sex-determining gene, even when the harm to benefit ratio is high. Genetic markers and artificial selection were used to make a pair of autosomal genes segregate like a new pair of sex-determining genes in a Drosophila melanogaster model system. A 29-generation study provides experimental evidence that sexually antagonistic genes may be common in nature and will accumulate in response to a new sex-determining gene. PMID- 1604318 TI - Lyme disease in California: a novel enzootic transmission cycle of Borrelia burgdorferi. AB - Knowledge of zoonotic transmission cycles is essential for the development of effective strategies for disease prevention. The enzootiology of Lyme disease in California differs fundamentally from that reported from the eastern United States. Woodrats, not mice, serve as reservoir hosts, and Ixodes neotomae, a nonhuman-biting tick, maintains the agent of Lyme disease, Borrelia burgdorferi, in enzootic cycles. The western black-legged tick, Ixodes pacificus, is the primary vector to humans, but it appears to be an inefficient maintenance vector. Isolates of B. burgdorferi from California exhibit considerable antigenic heterogeneity, and some isolates differ strikingly from isolates recovered from this and other geographic regions. PMID- 1604319 TI - Exhaustive matching of the entire protein sequence database. AB - The entire protein sequence database has been exhaustively matched. Definitive mutation matrices and models for scoring gaps were obtained from the matching and used to organize the sequence database as sets of evolutionarily connected components. The methods developed are general and can be used to manage sequence data generated by major genome sequencing projects. The alignments made possible by the exhaustive matching are the starting point for successful de novo prediction of the folded structures of proteins, for reconstructing sequences of ancient proteins and metabolisms in ancient organisms, and for obtaining new perspectives in structural biochemistry. PMID- 1604320 TI - Total chemical synthesis of a D-enzyme: the enantiomers of HIV-1 protease show reciprocal chiral substrate specificity [corrected]. AB - The D and L forms of the enzyme HIV-1 protease have been prepared by total chemical synthesis. The two proteins had identical covalent structures. However, the folded protein-enzyme enantiomers showed reciprocal chiral specificity on peptide substrates. That is, each enzyme enantiomer cut only the corresponding substrate enantiomer. Reciprocal chiral specificity was also evident in the effect of enantiomeric inhibitors. These data imply that the folded forms of the chemically synthesized D- and L-enzyme molecules are mirror images of one another in all elements of the three-dimensional structure. Enantiomeric proteins are expected to display reciprocal chiral specificity in all aspects of their biochemical interactions. PMID- 1604321 TI - Lymphoid development in mice congenitally lacking T cell receptor alpha beta expressing cells. AB - Vertebrate T cells express either an alpha beta or gamma delta T cell receptor (TCR). The developmental relatedness of the two cell types is unresolved. alpha beta + T cells respond to specific pathogens by collaborating with immunoglobulin producing B cells in distinct lymphoid organs such as the spleen and Peyer's patches. The precise influence of alpha beta + T cells on B cell development is poorly understood. To investigate the developmental effects of alpha beta + T cells on B cells and gamma delta + T cells, mice homozygous for a disrupted TCR alpha gene were generated. The homozygotes showed elimination of alpha beta + T cells and the loss of thymic medullae. Despite this, gamma delta + T cells developed in normal numbers, and there was an increase in splenic B cells. PMID- 1604322 TI - NF-kappa B subunit regulation in nontransformed CD4+ T lymphocytes. AB - Regulation of interleukin-2 (IL-2) gene expression by the p50 and p65 subunits of the DNA binding protein NF-kappa B was studied in nontransformed CD4+ T lymphocyte clones. A homodimeric complex of the NF-kappa B p50 subunit was found in resting T cells. The amount of p50-p50 complex decreased after full antigenic stimulation, whereas the amount of the NF-kappa B p50-p65 heterodimer was increased. Increased expression of the IL-2 gene and activity of the IL-2 kappa B DNA binding site correlated with a decrease in the p50-p50 complex. Overexpression of p50 repressed IL-2 promoter expression. The switch from p50-p50 to p50-p65 complexes depended on a protein that caused sequestration of the p50 p50 complex in the nucleus. PMID- 1604323 TI - Nerve growth factor stimulation of the Ras-guanine nucleotide exchange factor and GAP activities. AB - The biological activity of Ras proteins is thought to be controlled by the guanine nucleotide exchange factor and the guanosine triphosphatase activating protein (GAP). Treatment of rat pheochromocytoma PC-12 cells with nerve growth factor (NGF) increased the amount of active Ras guanosine triphosphate complex and stimulated the activities of both the guanine nucleotide exchange factor and GAP. In PC-12 cells that overexpressed the tyrosine kinase encoded by the trk proto-oncogene (a component of the high-affinity NGF receptor), the NGF-induced activation of the regulatory proteins was potentiated. These results suggest that the NGF receptor system enhances the activities of both the guanine nucleotide exchange factor and GAP and that the activation of Ras might be controlled by the balance in activity between these two regulatory proteins. PMID- 1604324 TI - Preliminary classification criteria for the antiphospholipid syndrome within systemic lupus erythematosus. AB - Ten percent of 667 consecutive systemic lupus erythematosus (SLE) patients were considered to have definite antiphospholipid syndrome (aPLS) because they had two or more antiphospholipid (aPL)-related clinical manifestations and aPL titers more than 5 SD above the mean of normal controls. Another 14% had either one aPL related manifestation but high titers of the antibody or two manifestations and low aPL titers (probable aPLS). One fourth of the patients had no manifestations but high titers, one manifestation and low titers, or two or more manifestations and negative aPL titers ("doubtful" aPLS); the other half were considered negative for aPLS. In patients with high-titer aPL, the number of aPL-related manifestations was influenced by disease duration and number of pregnancies, indicating potential mobility of category with time or with risk of recurrent pregnancy loss. Patients with two or more manifestations but variable aPL levels differed in immunosuppressive treatment and in the number of times they had been tested, indicating potential mobility of category with lower treatment and/or further aPL testing. Patients with definite aPLS had increased risk of cutaneous vasculitis, peripheral neuropathy, seizures, psychosis, transient ischemic attacks, and leukopenia. In 11 of 52 SLE patients with definite aPLS the initial manifestation was related to aPL, and in 16 it concurred with an unrelated one. Only two patients fulfilled criteria for aPLS before having other evidence of SLE. The authors conclude that aPLS occurring within SLE is part of the disease rather than an associated condition and propose the use of definite and probable classification categories. These criteria, with appropriate follow-up and clinical and serological exclusion clauses for potential primary conditions, could also be applied to primary aPLS. PMID- 1604325 TI - The impact of endpoint measures in rheumatoid arthritis clinical trials. AB - In clinical trials on the effectiveness of disease-modifying antirheumatic drugs (DMARDs) in patients with rheumatoid arthritis (RA), it is common to apply a large number of endpoint measures. This practice has several disadvantages. To determine which endpoint measures are most valuable, reports of 32 clinical trials on six DMARDs were reviewed. The frequency with which each endpoint measure was used is described and discussed, as well as the frequency with which the values of each endpoint were significantly different in statistical comparisons within or between groups, thus showing ability to discriminate between drugs not equally effective. The results of this review are discussed and compared with other reports in the literature on the choice of endpoint measures in RA clinical trials. The authors conclude that it is still common practice to evaluate multiple outcome measures. The number of measures could be reduced by using only those that are generally considered important, are sensitive to change, and are able to differentiate between drugs in clinical trials. A joint count, assessment of pain, a questionnaire on functional status, and measurement of erythrocyte sedimentation rate are sufficient. PMID- 1604326 TI - Spondyloarthropathy as an Old World phenomenon. AB - The presence of spine and sacroiliac involvement and the nature and distribution of erosive lesions allowed definitive diagnosis of spondyloarthropathy in the great apes (Gorilla and Pan [chimpanzee]), the lesser ape (Hylobates), and Old World monkeys (Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Erythrocebus). Analysis of lesional character, distribution, radiological appearance, and sex ratios showed a picture indistinguishable from human spondyloarthropathy. This contrasts with orangutans (Pongo), who lack reactive bone or sacroiliac involvement. A different pathophysiology, as yet undefined, is implied for their erosive arthritis. Limited individual susceptibility to spondyloarthropathy in humans (1% to 4%), Old World monkeys (2.4%), and lesser apes (2.4%) contrasts with the high frequency of disease in the great apes (20% to 28%). The wide geographic distribution of this phenomenon suggests an African and perhaps Asian "panendemic." This natural disease state provides a unique model for in-depth analysis of the contribution of genetic and environmental factors to disease pathophysiology. PMID- 1604327 TI - Regulation of the expression of adhesion molecules by human synoviocytes. AB - The capacity of synoviocytes to participate in inflammatory responses may be altered by the cytokine-enhanced expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1). To examine this possibility, the ability of selected cytokines to enhance ICAM-1 expression was examined. The data indicated that each of these cytokines (interleukin-1 beta greater than tumor necrosis factor-alpha, interferon-gamma much greater than interleukin-6) can up regulate synoviocyte ICAM-1 expression. This can potentially increase the ability of these cells to interact with infiltrating inflammatory cells, thereby propagating immunologically mediated inflammation such as occurs in rheumatoid synovitis. PMID- 1604328 TI - Synovium-like tissue from loose joint replacement prosthesis: comparison of human material with a canine model. AB - The formation of synovium-like tissue is a biological response to a loose joint replacement prosthesis. Histological examination of this tissue has shown a synovial lining with a predominance of fibroblasts and macrophages, some multinucleated giant cells, and dispersed particles from the implant. Previous studies have reported elevated interleukin 1 (IL-1), prostaglandin E2 (PGE2), and collagenase in this tissue. We developed a canine model for the loose cemented femoral stem. Tissue harvested from the canine model was compared with human tissue retrieved at revision arthroplasty. Histology showed synovium, similar to that observed around loose human prostheses, adjacent to the canine cement sheath. Cells were isolated from this tissue and incubated in culture medium with or without naproxen for 3 days. Aliquots of the conditioned media were tested in the thymocyte proliferation assay to determine IL-1-like activity. IL-1 beta levels in human cell-conditioned media were analyzed by enzyme-linked immunosorbent assay, and PGE2 levels were measured by radioimmunoassay (RIA) using a PGE2 RIA kit (New England Nuclear). Human tissue contained levels of IL-1 beta in the range of 150 to 7,040 pg/mL and PGE2 levels of 82 to 952 ng/mL. The canine specimens contained IL-1-like activity and significant amounts of PGE2 (76 to 1,720 ng/mL). Naproxen decreased PGE2 levels in vitro. This animal model provides the means to investigate the in vivo and in vitro activity of the synovial cells around loose total joint prostheses. PMID- 1604329 TI - [Instability of the atlantodental joint as a trauma sequela]. AB - In the region of the upper cervical spine a wide variety of morphological and functional positions is possible. This makes diagnosis and expert evaluation of whiplash injuries to the cervical spine very difficult. The problem is discussed with reference to a case report of a so-called whiplash injury. The upper cervical spine must be investigated in flexion and extension by means of MRT and/or CT as soon as possible. PMID- 1604330 TI - [Distal intra-articular humerus fractures in adults. Results of surgical treatment]. AB - Intra-articular fractures of the distal end of the humerus are severe injuries because stable anatomic reduction is difficult to achieve even operatively. They are often accompanied by nerve lesions and often lead to heterotopic para articular ossifications. Functional recovery is only rarely complete. Follow-up of 54 cases of operatively treated fractures of this kind showed 56% excellent and good late results. In immediate operations we observed fewer infections, less ossification, and better functional results than after delayed operative treatment. We therefore recommend careful examination for nervous deficits, immediate stable internal fixation of the fractures displaying the ulnar nerve, and handling the soft tissue as gently as possible to avoid additional damage. Postoperative physiotherapy should also be started immediately. PMID- 1604331 TI - [Hemi-arthroplasty of the hip joint: concentric or positive eccentric (self centering) dual head prosthesis? A retrospective comparison]. AB - In femoral neck fractures in the elderly, the least traumatic operative treatment is hemiarthroplasty. In our Trauma Unit, from August 1986 to December 1986 we implanted 22 concentric bipolar cups. During follow-up this cup proved to be associated with an unjustifiably high failure rate: system-caused interprosthetic dislocation in 4 patients (18%), and extraprosthetic dislocation in a further 3 (13%). In one of the latter, interprosthetic disconnection occurred during closed reduction. In all of these, i.e., in 31% out of the 22 patients, conversion to a total hip arthroplasty became necessary. Since March 1987 we have used a positive eccentric, self-centering bipolar head. Up to September 1990 322 such prostheses were implanted. Bearing in mind the reduced general physical condition of the patients, the complication rate is considered to be low (dislocations 3.4%, conversion to total hip arthroplasty 0.9%, deep wound infections 3.1%). PMID- 1604332 TI - ["Erlangen Model" titanium socket. Study of the biomechanics of the "Erlangen Mode" titanium socket with and without supporting ring]. AB - A multitude of prostheses are available for the reconstruction of severely arthrotic hip joints--especially for revising total arthroplasty. In order to find out more about the biomechanical efficiency of these special implants, we carried out computerized analyses on how the distribution of stress within the pelvis changes when employing the titanium socket component "Erlanger Modell" [TiAl 5 Fe 2.5], which can be used with a supporting ring in order to transfer the stress on the hip joint to the iliac bone and to the pubic bone in case the acetabulum should not be able to provide the stability needed by the socket. In a procedure described by Herzog, strain gauges are attached to the pelvis of freshly slaughtered cattle at the following sites, transmitting the relative bone expansion and torsion to a multipoint measuring instrument (Linseis L2100) and on line to a computer: (1) superior ramus of the pubic bone; (2) front edge of the socket at the iliopubic eminence; (3) iliac bone on the outside of the pelvis; (4) socket roof, pars ossis ilei in the small pelvis; (5) socket roof, pars ossis ischii in the small pelvis. The quality of the implantation was monitored by the non-delayed force transmission from the femur through the hip arthroplasty onto the pelvis. With stress varying from 0 to 500 N in steps of 125 N we carried out four complete readings in order to ensure the reproducibility of the measurements.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1604333 TI - [Implantation technique of tumor and crutch prostheses]. AB - Using anatomic specimens from 58 fixed femurs, we analyzed the point of insertion and junctional variations of the gluteus medius, minimus and vastus lateralis over the greater trochanter. On six specimens the physiological muscle cross section Q was determined for the muscles inserting at the greater trochanter. The results showed that the gluteus medius and minimus, as well as the vastus lateralis generally insert at the lateral and ventral surfaces of the greater trochanter. In 59.6% of all cases these muscles form a joint tendon junction. In 21.1% the gluteus medius inserts autonomously and with 13.5% the gluteus minimus inserts independently. In 5.8% of all specimens all three muscles insert autonomously. The average physiological muscle cross-section of the gluteus medius and minimus added up to 37.83 cm2 and that of the vastus lateralis and the fibrously connected vastus intermedius came to 36.14 cm2. Accordingly the extensor muscles of the knee, together with the counteracting gluteus medius und minimus, form a muscle sling that puts a pressure load on the greater trochanter from the lateral cranial direction. An operating technique for the implantation of tumor prostheses using this muscle sling is introduced. Hereby the greater trochanter and inserted musculature remain intact and are placed hoodlike on the implanted tumor prosthesis. Postoperatively, the procedure results in good muscle function with early exercise tolerance. PMID- 1604334 TI - [Bilateral femoral fracture at the site of bilateral hip prostheses. A case report]. AB - Fracture of the femoral shaft after hip arthroplasty is a serious problem. In most cases, minimal trauma is responsible for the fracture. Predisposing factors include severe osteoporosis, loosening of the prosthetic stem and perforations of the cortex. The incidence in our patient material in 2.3% after total hip arthroplasty and 2.9% after revision. Operative treatment may consist in osteosynthesis with compression plates, screws, or cerclage wires with or without revision of the arthroplasty. We give a case report covering treatment and 2-year follow-up for a bilateral proximal femoral fracture in a 72-year-old farmer with bilateral total hip replacements. Both fractures were treated similarly, with replacement of the femoral components by a cementless Wagner revision stem prosthesis and cerclage wiring of the fragments. No classic osteosynthesis was required to manage the fractures. PMID- 1604335 TI - [Injury of the inguinal blood vessels in implantation of hip joint prosthesis]. AB - Vascular injuries during or after total hip replacements have often been reported. In 2257 artificial hip joint replacements, we observed 8 cases of vascular injuries requiring reconstruction (3 cases), suturing (2 cases), end-to end anastomosis (1 case), or ligature (2 cases) performed by a vascular surgeon. A separate skin incision for vascular repair was necessary in all patients. Most of the injuries occurred as a result of technical errors through lack of caution when using bone hooks or rough handling, resulting in dislocation of the hip joint. The latter occurs mainly in revision procedures. Six patients recovered fully, but two died, one of hemorrhagic shock and the other of cardiac decompensation. PMID- 1604336 TI - [Early and late results of 200 DHS osteosyntheses in the reconstruction of pertrochanteric femoral fractures]. AB - We have treated more than 600 cases of trochanteric fractures by internal fixation with the dynamic hip screw. Between 1986 and 1988 we treated exactly 200 patients in this way, who were subsequently observed over follow-up times averaging 24 months. In 1% of this group we performed early revision osteosynthesis because of incorrect positioning of the lag screw; deep infections occurred in 2.5%; and in 6% revision interventions were necessary because of local hematomas. Late complications were necrosis of the femoral head (1%) and pseudarthrosis after head necrosis (0.5%). No reinterventions were necessary because of implant failure. PMID- 1604337 TI - [A cellular quantitative immune deficiency in chronic post-traumatic osteomyelitis]. AB - The specific cellular host defence in patients with chronic post-traumatic bone infection was analyzed in a prospective study. The study included 120 patients with chronic post-traumatic osteomyelitis and 60 healthy volunteers. The number of CD-5, CD-4, CD-8, natural killer cells and the CD-4/CD-8 ratio were significantly decreased. The immunodeficiency seems to be trauma-induced and reinflammation seems to be due to other immunodeficient factors. The potential key role of a defect in cytokines is discussed. PMID- 1604338 TI - [Antibiotic-containing collagen sponge in therapy of osteitis]. AB - In 1988, we treated 47 patients with acute or chronic osteitis by means of a new industrial collagenous sponge containing gentamicin (Sulmycin Implant) as an adjuvant measure. The local surgical management was standard: total excision of all avascular or infected soft tissue and bone, stabilization of pseudarthrosis, the improvement of local circulation and the condition of the soft tissue by means of local or free flaps before autologous bone grafting and antibiotics administered according to the test results. In cases of instability AO external fixation was used. One or two Sulmycin Implants (10 x 10 cm) containing 130 or 260 mg gentamicin were placed in the remaining small cavities or in the transplanted autologous spongy bone. Gentamicin was measured in the wound exsudate for 3-5 days; during this time we found bactericidal concentration in these exsudates. The wounds healed in 44 patients, but we had a persistent fistula in 3 patients (6.3%). We see collagen-gentamicin sponges as being very useful in the treatment of osteitis. It seems to reduce delayed bone transplantation in infected areas. PMID- 1604339 TI - Posttraumatic calcification of the annular ligament of the radius. AB - Eight cases of calcification following anterior dislocation of the head of the radius are described. It was demonstrated as early as 2 weeks after injury and in 7 cases appeared in the form of a shell on the volar aspect of the head. The other type exhibits a cuff of calcification related to the radial neck. Parallel cases are drawn from a literature review, and the distinction is made between calcification in the disrupted annular ligament/capsule or oblique cord and myositis ossificans. Regression in several cases may be a consequence of open reduction. PMID- 1604340 TI - Radiological appearances following limb replantation: a report of 5 cases. AB - Plain radiographs of the limbs were reviewed after replantation procedures following traumatic amputation in 5 patients at the wrist (2), mid-forearm (2) and knee (1). Following upper limb replantation, rapid development of osteopaenia was initially noted in the juxta-articular regions and metaphyses of the tubular bones of the hand. These changes were followed by diaphyseal cortical bone loss with evidence of subperiosteal, intracortical and endosteal bone resorption. Juxta-articular erosions developed at the margins of the small joints in the hand in all cases. Gradual resolution of bone changes was noted in 3 of the 4 cases where follow-up exceeded 5 years. Following lower limb replantation, there was no evidence of bone loss; however, severe neuropathic joint disease developed within 18 months and progressed over the following 9 years. We suggest that the radiographic changes observed after upper limb replantation reflect regional hyperaemia secondary to neurovascular damage, whilst the changes in the lower limb reflect a similar process in a limb subjected to weight bearing. PMID- 1604341 TI - Bone excrescence at the medial base of the distal phalanx of the first toe: normal variant, reactive change, or neoplasia? AB - In a review of 157 anteroposterior (AP) foot radiographs in 117 adult and pediatric patients, we observed a medial excrescence on the plantar aspect of the terminal phalanx of the hallux in 88.5% of the feet. Histologic analysis documented the presence of reactive bone. The bony outgrowth appears after closure of the adjacent physeal plate and is rarely symptomatic. Its high prevalence indirectly implies that it is not specific to any particular type of foot. Although certain types of foot may contribute to its development, we believe that repetitive forces occurring during ambulation induce this reactive bone formation. PMID- 1604342 TI - Aneurysmal bone cysts treated by superselective embolization. AB - A series of 7 cases of aneurysmal bone cysts (ABC), all but 1 located in the pelvic bones, which were treated by transcatheter embolization is presented. Five embolizations were performed for primary treatment, while in 2 patients they were performed preoperatively. In all patients a definite histological diagnosis was established by open biopsy, and plain radiographs as well as computerized tomography (CT) were applied for evaluation of the results. The embolizing materials were tissue adhesive for permanent, and Gelfoam for preoperative vessel occlusions. Of 5 lesions treated for the purpose of definitive embolization, 3 (all located in the superior pubic ramus) showed complete ossification; in one, partial remineralization and progression occurred. In a further patient with a secondary ABC, partial reconstitution was recorded. Both preoperative embolizations resulted in successful en bloc resection with minimal blood loss. Transcatheter embolization is the treatment of choice for the highly vascular ABC in unfavorable anatomical locations. PMID- 1604343 TI - Femoral stress fractures in children. AB - Stress fractures reported in the medical literature almost exclusively affect young athletes, military recruits and patients with metabolic bone disease. The classification of stress-induced bone injury is somewhat confused and includes "fatigue" stress fractures which occur in previously normal bones and "insufficiency" stress fractures which occur in bones weakened by various causes. Femoral stress fractures in children are extremely rare, and we report 5 cases in young patients who sustained their injuries during the course of normal play activities. It is well-known that these lesions can simulate malignant lesions; however, we believe that careful review of the radiographs in the context of the clinical history can in many cases lead to the correct diagnosis being made and obviate the need for further intervention. PMID- 1604344 TI - Osteoma of soft parts. AB - Osteomas of soft tissue are rare tumors. All previously reported cases occurred in the head, usually in the posterior tongue. We present two patients with soft tissue osteomas in the thigh. Both masses were densely ossified and consisted of mature trabecular bone on computed tomography and magnetic resonance examination. Increased uptake of bone-seeking radiopharmaceutical was found on scintigraphy. Histologically, mature lamellar bone was seen with small amounts of cartilage seen in the periphery. Symptoms of mass effect which resolved following surgery were noted. We believe that this previously unrecognized soft-tissue appendicular neoplasm lies at the end of a spectrum of post-traumatic ossifying lesions which includes soft-tissue chondromas and osteochondromas, as well as myositis ossificans. PMID- 1604345 TI - Case report 705. Osteosclerotic sarcoidosis. AB - In summary, Sarcoidosis is a rare but well-recognized cause of diffuse osteosclerosis. The differential diagnosis of osteosclerosis is limited and includes osteoblastic metastases, sclerotic myeloma, myelofibrosis, and less common infiltrative bone marrow processes such as mastocytosis and sarcoidosis. In all of these entities the sclerosis is found most often in the axial (red marrow) skeleton. In this regard, it is interesting that cases of osseous sarcoid are usually lytic and located in the peripheral skeleton. In patients with osteosclerotic sarcoidosis, the diagnosis may be suggested by a past history of the disease or ancillary signs such as hilar node enlargement and subtle skin involvement. However, the specific diagnosis usually requires bone marrow biopsy with the demonstration of extensive, noncaseating granulomas. PMID- 1604346 TI - Case report 722. Osteosarcomatosis in a skeletally immature girl. AB - We report a case of a clinically and radiographically dominant osteosarcoma of the proximal end of the tibia, in which the second skeletal focus of osteosarcoma was apparent on MRI, after having escaped detection on routine radiographs and scintigraphy. Detection of the second lesion significantly altered the subsequent treatment and prognosis. The improved sensitivity of MRI may increase the accuracy of the diagnosis of osteosarcomatosis. Although further study is needed, MRI study of long bones, especially T1-weighted images in the coronal plane, may be considered as a screening procedure to exclude occult skeletal involvement in patients with osteosarcoma and negative standard metastatic evaluation. PMID- 1604347 TI - Case report 723. Popliteal artery aneurysm. AB - An unusually large, noncalcified popliteal artery aneurysm causing cortical erosion was erroneously diagnosed as a soft-tissue sarcoma. The case stresses the importance of excluding a vascular cause of a mass whenever biopsy is considered. We review the clinical and radiological features of popliteal artery aneurysm and describe the appearance of the aneurysm on MR. PMID- 1604348 TI - Case report 724. Yaws. AB - A 15-year-old girl presented with the typical clinical, serological, and pathological lesions of yaws. The patient was a native of Sumatra. The important diagnostic criteria and the relationship to venereal syphilis were discussed. PMID- 1604349 TI - Case report 725. Posterior displacement of proximal end of the right radius and capitulum with supracondylar fracture causing a displaced fracture rather than a fracture dislocation. AB - An 11-month-old boy with a swollen, painful right elbow demonstrated a supracondylar fracture on plain film radiographic studies. Sonography was subsequently performed to exclude dislocation of the elbow and demonstrated the supracondylar fracture as well as a normal relationship of the capitulum and radius, signifying a displaced fracture without associated dislocation. A bone dislocation would generally require dosed reduction alone, whereas distal humeral epiphyseal separation usually requires open reduction or percutaneous (pin) fixation. This case demonstrates the utility of ultrasound in the evaluation of physeal disruption and dislocation in the elbow prior to ossification of the secondary centers of ossification. PMID- 1604350 TI - Case report 726. Enchondromatosis of the left femur and hemipelvis (Ollier's disease). AB - A case of Ollier's disease is demonstrated. Large osteolytic lesions in the left femur and hemipelvis visible on the roentgenograms represent enchondromas. On CT and MRI studies numerous fine translucencies are demonstrated in the surrounding bone, corresponding to multiple cartilaginous foci. These findings may be considered pathognomonic for enchondromatosis (Ollier's disease). In addition, the nature of Ollier's disease and its predilection for malignant transformation are considered. The major differential diagnostic entity in this case was probably fibrous dysplasia. PMID- 1604351 TI - Case report 727. Juxtacortical adamantinoma of humerus (simulating Ewing tumor). AB - A case of adamantinoma of the humerus with Ewing-like pathological features has been reported. In addition to the unusual pathological features, the apparently juxtacortical location of the lesion is of great interest--also a highly unusual feature for an adamantinoma. PMID- 1604352 TI - Allocating medical resources in rural America: alternative perceptions of justice. AB - In national debates concerning the allocation of medical resources rural America is a neglected topic, and the voices of rural health professionals are seldom heard. This paper highlights the special problems encountered in allocating medical resources within the rural setting and indicates the strategies that rural residents compose for dealing with them. Our findings are based on a study consisting of in-depth open-ended interviews with family physicians in the rural northwest United States. We contrast the approach to justice expressed by these rural physicians with the conception of justice that dominates Western philosophy and bioethics. In the course of our discussion, the diversity within Western culture becomes apparent. We discuss strategies for incorporating different perspectives into local and national allocation debates, clarify the reasons why a more encompassing approach to justice is necessary, and review the implications of our work for future research. PMID- 1604353 TI - AIDS: conceptual and methodological issues in researching sexual behaviour in sub Saharan Africa. AB - This paper describes some of the conceptual and methodological issues encountered in the course of a study of mainly anthropological secondary source materials on sexual behaviour in sub-Saharan Africa. Its aim was to survey and review existing literature and other secondary sources available both outside and within Anglophone sub-Saharan Africa and to evaluate their usefulness to AIDS research and prevention. The review cautioned against the uncritical use of anthropological sources without due regard for their conceptual and methodological status. At the same time it demonstrated important ways in which anthropological insights can inform AIDS research. PMID- 1604354 TI - Cultural change and the reproductive cycle. AB - What we regard as 'normal' or 'natural' with respect to human female reproductive physiology differs greatly from the reproductive cycle experienced during most of human existence. Frequent ovulatory menstrual cycles really represent repeated abortive reproductive cycles and are unphysiological. A number of medical conditions, some of great importance, are the result of this change in the character of the reproductive cycle. Suppression of the menstrual cycle offers a means of decreasing the incidence and severity of these medical conditions. PMID- 1604355 TI - Why do the O'Sheas consult so often? An exploration of complex family illness behaviour. AB - Complex illness behaviour can be seen as a product of dysfunctional communication between doctors and patients. A methodology to understand such behaviour is described: it uses case record analysis and meetings with patients and health teams to create a set of family trees and graphs of consultation patterns; these are the basis on which to generate and test hypotheses. This model is used to explore the consultation rates of a family between the 1940s and 1988. Illness behaviours increased rapidly during the 1980s at a time when both the family and their general practitioners were undergoing rapid changes and losing significant members. Mutually unacknowledged depression may have been a key factor. Strategies for change are suggested. PMID- 1604356 TI - Identity, ideology and medicine: health attitudes and behavior among Hindu religious renunciates. AB - In-depth interviews and participant observation was conducted with 14 Hindu religious renunciates, 70 years or older. Despite having taken vows renouncing concern for physical pain or comfort, respondents differed markedly in their attitudes toward pain and their rationale for utilizing medical treatment. They differed still further in their use of Ayurvedic and allopathic medicine, with the most culturally conservative accepting only Ayurvedic medicine. Rejection of allopathic medicine tended to be associated with a highly systematized religious world-view. The results are discussed in terms of both the ideological conflict between religious world-view and medical usage, and the need for sophisticated distinction of religious world-view if research on the religious factor of health care utilization is to prove fruitful. PMID- 1604357 TI - Patient non-compliance: deviance or reasoned decision-making? AB - A large quantity of research concerning issues of patient compliance with medications has been produced in recent years. The assumption in much of this work is that patients have little option but to comply with the advice and instructions they receive. Studies have shown, however, that between one third and one half of all patients are non-compliant, but different authors cite different reasons for this high level of non-compliance. In this paper, the concept of compliance is questioned. It is shown to be largely irrelevant to patients who carry out a 'cost-benefit' analysis of each treatment, weighing up the costs/risks of each treatment against the benefits as they perceive them. Their perceptions and the personal and social circumstances within which they live are shown to be crucial to their decision-making. Thus an apparently irrational act of non-compliance (from the doctor's point of view) may be a very rational action when seen from the patient's point of view. The solution to the waste of resources inherent in non-compliance lies not in attempting to increase patient compliance per se, but in the development of more open, co-operative doctor-patient relationships. PMID- 1604358 TI - An appraisal of the current status of communication skills training in British medical schools. AB - The present study surveyed medical schools in Britain to critically evaluate the current status of communication skills training in medical education. Results indicate that though all respondents provide some form of communication skills training for students, relatively few are committed to formal instruction, assessment, and evaluation of the subject within the medical curriculum. The methods and objectives of training are considered in terms of effective learning and skills acquisition, with reference to training and learning literature. The findings are discussed within the wider issue of social science in medicine; it is argued that there is a real need for critical assessment which should be linked to professional advancement. PMID- 1604359 TI - Competing explanations for associations between marital status and health. AB - This paper is based on baseline data from a survey of 1042 fifty-five year olds living in the Central Clydeside Conurbation, who constitute the eldest cohort of the 'West of Scotland Twenty-07 Study'--a longitudinal study of health and everyday life. The relationship between marital status and a number of measures of health and illness is explored. The paper examines which of four 'social causation' explanations--that married people have better health because they have more material resources, less stress, indulge in less risky health behaviour and have more social support--can actually account for the observed patterning. It finds that more risky health behaviour (measured by smoking and drinking), and 'objective' levels of social support, cannot account for very much of the effect of marital status on health measures; but that material resources, stress and perceived quality of social support could do so. However, elucidation of the direction of the relationships between these explanations and health measures, and indeed of the effect of health 'selection' into and out of marriage must await future sweeps of this longitudinal study. PMID- 1604360 TI - Guatemalan Indian children and the sociocultural effects of government-sponsored terrorism. AB - The effects of government-sponsored terrorism, characteristic of the contemporary Central American civil wars, are particularly devastating to children. In Guatemala, the Mayan population felt the worst of a systematic and brutal counterinsurgency, where over 400 rural villages were destroyed between 1981 and 1983. This research is intended to elucidate selected characteristics of the psychosocial trauma of civil war as experienced by Guatemalan Mayan children, to describe some of the sociocultural effects of civil war on the children's Mayan ethnic identity and to identify those factors that helped them to survive severe trauma and loss. Specifically, during the summer of 1988, 32 children in Guatemala and 36 exiled in Mexico, between the ages of 8 and 16, participated in research designed to compare the negative effects of civil war and the adaptive capabilities of children who have experienced the trauma of the loss of immediate family members, the witnessing of violent crimes and the displacement from their homes. In addition to a semi-structure, open-ended interview and taped personal story/testimonies, several traditional psychological instruments were used to facilitate our understanding of the overall well-being of these children who have been affected by systematic violence. The long-term effects of this trauma cannot be fully anticipated, but the results suggest that these children suffer an abiding fear and face many uncertainties. The children in the orphanages in Guatemala have few expectations for the future and those in refugee camps in Mexico see a bleak future with few opportunities besides survival. The training and preparation of community mental health workers is a realistic possibility with positive effects for the psychic health of the children. PMID- 1604361 TI - Does the current use of junior doctors in the United Kingdom affect the quality of medical care? AB - Current proposals in the U.K. envisage a reduction in both junior staff numbers and the hours which they work. The proponents of change argue that this will improve patient care, although there are also opposing arguments, based mainly on the need to maintain continuity of care and ensure juniors gain sufficient clinical experience. By means of a literature review and interviews with junior doctors, this paper examines the effect of the existing system of hospital medical staffing on quality of care. There is evidence that the existing system reduces the quality of care, principally through mistakes associated with inadequate supervision, and lowered humanity of care due to tiredness. The training value of night-time and weekend work is low, and many doctors find it unsatisfying. In contrast, many doctors value providing continuity of care and a few appreciate the opportunity to gain unsupervised experience. Overall, the disadvantages of the existing system outweight the advantages, and change is required to improve the quality of care. There are, however, several obstacles to change, and there are doubts about the extent to which the current proposals will be implemented. PMID- 1604362 TI - Methods for quality adjustment of life years. AB - Several valuation techniques are in use for quality adjusting life years in cost utility analysis. The paper gives an overview of the variability in results. A close inspection of a number of instruments with respect to their theme, instructions, decision framing and the phrasing of questions make many of the observed differences in results understandable. When judging the validity of the different techniques, three points should be kept in mind. One is that statements about validity should be made with respect to concrete versions rather than broad categories like 'the rating scale', 'time trade-off' etc. Another point is that a valuation technique that is valid in clinical decision analysis may not be valid in health program evaluation, and vice versa. The third point is that quality weights for life years are empirically more meaningful, in the sense that they are more amenable to empirical testing, if they are interpreted simply as preference weights rather than measures of amounts of well life in the utilitarian tradition. Time trade-off with a moderate time horizon is recommended in clinical decision analysis, while a combination of time trade-off and a variant of person trade-off is recommended in health program evaluation. PMID- 1604363 TI - Going public as an AIDS family caregiver. AB - Images of AIDS invoke fears of contagion, disability and formidable death, and moral overtones directed toward drug use, sexuality and sexual identity and freedom. Responses to these images are both private and public, and have profound consequences for individuals whose lives have been touched by the disease, both the person with AIDS and the family caregiver. The purpose of this paper is to analyze in detail 'going public,' one category of a substantive theory of AIDS family caregiving. This category was developed from a grounded theory study of 53 AIDS family members who were asked to describe their experiences as an AIDS family caregiver during an indepth interview. Data were content analyzed using constant comparative analysis. Going public referred to how AIDS family caregivers let others known that they were caring for a PWA. Specifically, going public entailed selecting appropriate persons and audiences to tell, formulating approaches to communicating information, and considering the risks and benefits of the possible choices. The description of going public as an AIDS family caregiver details the assertiveness involved in political action and social change, contrasted with the isolation and secrecy involved in maintaining relationships with others under the condition of a stigmatizing illness. Data revealed a particular emphasis on the phenomenon of 'guilt by association'. Because of their close relationship to a person with AIDS, caregivers were obligated to share the stigma of AIDS and were likewise discredited. Findings from our study emphasize the tremendous personal suffering experienced by caregivers which was associated with AIDS stigma in the form of rejection, loss of friends and harassment. Data also revealed the strong commitment of many caregivers to social activism which ranged from participating in educational efforts to marching in demonstrations. The rationale for the apparent increased activism among AIDS family caregivers compared to other groups of caregivers is explored. Going public highlights both the personal suffering and social manifestations of AIDS, significant issues to consider in planning health services for the second decade of the AIDS epidemic. PMID- 1604364 TI - Constructing a canon? PMID- 1604365 TI - Ethical, methodological, and political issues of AIDS research in Central Africa. PMID- 1604366 TI - Militarism and world health. AB - Militarism is a rapidly growing factor in that complex network of social, political and economic causes of ill health among the world's poor. This complex of causes is driving a spiral of class inequality, political instability, and military repression in many less developed nations. These nations share a uniform security doctrine, which has major health impacts. Here five impacts are noted: diversion of resources, suppression of dissent, military classism, environment damage, and crime and terrorism. The demand stimulated by the recent Persian Gulf War for expensive, high-technology weapons may deepen Third World debt and fuel the cycle of poverty, ill health, social unrest, and military oppression. International health workers need to take account of the causes and effects of militarism in their studies of health problems. Their work could be aided by organizations that promote disarmament and environment preservation. PMID- 1604367 TI - Time prices and the demand for GP services. AB - This paper analyzes the effects of time prices on the demand for general practitioner (GP) services. Where data on earnings per unit of time was not available, an alternative method was used to impute the value of time. Separate elasticities were estimated using interactive dummy variables for individual employment status. Furthermore, a distinction was made between patient-initiated and physician-initiated visits to a GP. The results show that the probability of a patient-initiated visit is negatively influenced by the time required, for 4 of the 6 employment status categories defined. For a subsample, time was valued on the basis of earnings per time unit. The resulting time price was found to have a significant negative impact on the probability of a patient-initiated visit to a GP. However neither time nor time prices have any effect on the probability of a physician-initiated visit. It can therefore be concluded that time prices are a relevant factor in the determination of demand for GP services, particularly if it is the patient who is making the decision. Ignoring time prices could result in the mis-specification of demand equations, obtaining biased results from statistical analyses and wrongly assessing policy implications. PMID- 1604368 TI - Work-health relationships in middle-aged and elderly residents of a Jerusalem community. AB - Work-health relationships were examined cross-sectionally in 1886 men and women aged greater than or equal to 50 years in Jerusalem in 1985-1987, in the third round of a multipurpose longitudinal community health study. The main occupational variables were employment status, reasons for not working, and satisfaction with work. Sex and age were controlled in all comparisons. Workers were clearly healthier than nonworkers with respect to general, physical and emotional health, and people who had given up work were less healthy than those still working, whether they had stopped for health reasons, only because of their age, or only for extrinsic reasons (retrenchment or dismissal). Workers who expressed satisfaction with their work were healthier than others, the odds ratio in favour of good general health being 2.4 at 50-64 and 2.5 at greater than or equal to 65 years of age. The associations between job satisfaction and health remained apparent when education and origin were controlled. Multivariate analyses suggested that the associations were not spurious ones attributable to proneness to report both dissatisfaction and ill-health. Job dissatisfaction was not significantly associated with angina pectoris, possible myocardial infarction, or hypertension. Taken at their face value, the findings support the impact of job satisfaction or its determinants on the health of middle-aged and elderly men and women. The associations will be re-appraised in the longitudinal analysis of the study data. PMID- 1604369 TI - Status incongruence and serum cholesterol in an English general practice. AB - The relationship between status incongruence and serum cholesterol was examined in a case-control study carried out in an English general practice population. Patients (n = 54) with elevated serum cholesterols (greater than or equal to 7.0 mmol/l) were compared to age and sex matched controls (n = 54). A specific type of status incongruence--lifestyle incongruity--was measured as the degree to which style of life (material consumption and status-enhancing behaviors) exceeded occupational status. Lifestyle incongruity was associated with higher serum cholesterol and an increased odds of being a case. This association was independent of age, sex, the body mass index, family history of cardiovascular disease, alcohol use, and, for women, menopausal status. Implications of these results for research on social inequality and the risk of cardiovascular disease are discussed. PMID- 1604370 TI - Life events and daily hassles and uplifts as predictors of hospitalization and outpatient visitation. AB - Increased occurrence of major life events and daily "hassles" and "uplifts" have been shown to be associated with several measures of health status and health care utilization. In order to test for such an association with hospital admission, a prospective study was designed. Navajo Indians presenting for either inpatient or outpatient health care at a U.S. Indian Health Service facility were questioned regarding the occurrence of major life events in the preceding six months and of hassles and uplifts in the preceding week. Two years later the subsequent numbers of outpatient visits and of hospital admissions were determined for each subject. An increased number of either major life events (relative risk 1.66) or daily hassles and uplifts (relative risk 1.87) was found to be associated with an increased risk of hospital admission. The effects of major and daily life events were additive on the risk of admission. In addition, hassles were predictive of subsequent outpatient utilization. While further demonstrating the influence of major and daily life occurrences on health care utilization, this study also shows their importance in an additional cultural setting. PMID- 1604371 TI - Distance and risk measures for the analysis of spatial data: a study of childhood cancers. AB - Three statistical approaches, used to detect spatial clusters of disease associated with a point source exposure, are applied to childhood cancer data for the city of San Francisco (1973-88). The distributions of incident cases of leukemia (51 cases), brain cancer (35 cases), and lymphatic cancer (37 cases) among individuals less than 21 years of age are described using three measures of clustering: distance on a geopolitical map, distance on a density equalized transformed map, and relative risk. The point source of exposure investigated is a large microwave tower located southwest of the center of the city (Sutro Tower). The three analytic approaches indicate that the patterns of the major childhood cancers are essentially random with respect to the point source. These results and a statistical model for spatial clustering are used to explore distance and risk measures in the analysis of spatial data. Both types of measures of spatial clustering are shown to perform similarly when a specific area of exposure can be defined. PMID- 1604372 TI - Social relationships and health: the relative roles of family functioning and social support. AB - The associations between social relationships and health have been examined using two major research traditions. Using a social epidemiological approach, much research has shown the beneficial effect of social supports on health and health behaviors. Family interaction research, which has grown out of a more clinical tradition, has shown the complex effects of family functioning on health, particularly mental health. No studies have examined the relative power of these two approaches in explicating the connections between social relationships and health. We hypothesized that social relationships (social support and family functioning) would exert direct and indirect (through depressive symptoms) effects on health behaviors. We also hypothesized that the effects of social relationships on health would be more powerfully explicated by family functioning than by social support. We mailed a pilot survey to a random sample of patients attending a family practice center, including questions on depressive symptoms, cardiovascular health behaviors, demographics, social support using the ISEL scale, and family functioning using the FEICS scale. FEICS is a self-report questionnaire designed to assess family emotional involvement and criticism, the media elements of family expressed emotion. Eighty-three useable responses were obtained. Regression analyses and structural modelling showed both direct and indirect statistically significant paths from social relationships to health behaviors. Family criticism was directly associated (standardized coefficient = 0.29) with depressive symptoms, and family emotional involvement was directly associated with both depressive symptoms (coefficient = 0.35) and healthy cardiovascular behaviors (coefficient = 0.32). The results support the primacy of family functioning factors in understanding the associations among social relationships, mental health, and health behaviors. The contrasting relationships between emotional involvement and depressive symptoms on the one hand and emotional involvement and health behaviors on the other suggest the need for a more complex model to understand the connections between social relationships and health. PMID- 1604373 TI - Female labour participation in agricultural production and the implications for nutrition and health in rural Africa. AB - The broad objectives of this paper are: firstly, to examine the initial impact of colonialism on food production by women, by considering their role and activity patterns within the household in terms of rights, obligations, exchanges, allocation of resources and responsibilities and the division of labour in the selected African Societies of the Luo, Kikuyu and Luhya (Kenya), Ewe and Kusasi (Ghana), Mandinka (The Gambia), Yoruba (Nigeria) and Azande (Sudan). These ethnic groups used as examples were mainly selected on the basis of their predominance and availability of data in these countries lying in the Sub-Saharan Africa having similar historical roots of the British colonial policies. Secondly, some of the possible social, economic and biological effects or implications on the changes in rural women's work in the chosen case studies in Africa are elucidated. It has been hypothesized that the development process in rural Africa has marginalized women (with varying degrees) in the subsistence sector, reducing their productivity and control over resources; and that women's total work burden has relatively increased, a phenomenon which can be understood as an integral process of capital penetration and accumulation. These changes may have significant implications for nutrition and health affecting the overall levels of food production. Although the selected illustrations do not represent the full range of possibilities in Sub-Saharan Africa, the data on the gender roles and workpatterns and the different changing ways do indicate that the women's role in food production has profound implications for socio-economic development in general and nutrition and health in particular with much wider applicability. In fact no such cross-sectional study has been conducted in rural Africa. It is generally concluded that any consideration of women's agricultural production should not neglect the structural bases of their inequality, and the policies can be inadequate if they overlook the relationship between the subsistence and commercial sectors and the women's role in each. In effect, the relative and absolute losses in women's food production and incomes bear immediately on the food crisis of many of the Sub-Saharan African countries, and that the current policies for the food crisis are likely to fail unless there is an improvement of the data base in women's and men's specific food production activities, processing and marketing for use in policy formulation and implementation. Indeed, the integration of women into the development process should be sensitive to and cognizant of their needs, contributions and potentials in Sub-Saharan Africa. PMID- 1604374 TI - Household decisions among the Gogo people of Tanzania: determining the roles of men, women and the community in implementing a trachoma prevention program. AB - An epidemiological survey in rural Tanzania indicated that the rate of trachoma was elevated in children whose faces were unclean. To aid in designing a health education program to increase face washing, a descriptive village study was done to determine water use patterns, attitudes towards face washing, responsibility for child hygiene, and decision making processes in the household and community. The study found that mothers were responsible for both water use and the health and cleanliness of the children. However, health education could not be directed at the women alone because the decision to change behavior had to be sanctioned by the husband in the household, and the community as a whole. The final health campaign was designed to be compatible with the accepted patterns of decision making. This case study, as well as others which focus on women's groups as change agents, suggests several factors such as male migration and local authority structures which health planners may need to assess when designing health programs. PMID- 1604375 TI - More resources better health? A cross-national perspective. AB - This study is an attempt to examine the relative importance of health care resources in predicting infant mortality within industrialized, developing, and underdeveloped countries. The analyses were based on the data of 117 countries. Findings from this study suggest that health resources as a whole do not make a significant contribution to accounting for the variance of infant mortality rates over and above the variance accounted for by socioeconomic resources only. The contribution of health resources to the health of the population as a whole is really rather small in comparison to the role of socioeconomic resources. PMID- 1604376 TI - Behavioral risk factors for sexually transmitted diseases in American households. AB - The analysis of a representative survey of households (n = 968) in a San Francisco Bay Area county provides strong evidence for the role of problem drinking as a risk factor for sexually transmitted diseases independent of drinking patterns and drug use. Among women, age, race, early age at first intercourse, history of multiple partners, drinking patterns, as well as current symptoms of problem drinking were all associated with reported STD rates. Stepwise logistic regression analysis showed, however, that female problem drinkers are nearly four and a half times more likely (adjusted O.R. = 4.65, 95% C.I. = 1.30, 16.70) than other women to have had STDs independent of all these potential risk factors. Problem drinking puts women at a greater risk for STDs than a history of multiple sex partners (adjusted O.R. = 2.75, 95% C.I. = 0.98, 7.75). This finding is also observed among men, among whom STDs were associated with a history of multiple sex partners (adjusted O.R. = 4.12, 95% C.I. = 1.90, 8.94) and the lifetime prevalence of drinking problems (adjusted O.R. = 4.95, 95% C.I. = 2.13, 11.50). Frequent bar-going, drunkenness episodes, high volume drinking, feeling disinhibited while drinking and drug use increase the risk for STDs via their effects on the rate of sex partner change. Problem drinking determines STD rates independent of these factors. The implications of these findings for future research and health policy are discussed. PMID- 1604377 TI - Yellow fever epidemics and mortality in the United States, 1693-1905. AB - Yellow fever epidemics struck the United States repeatedly in the 18th and 19th centuries. The disease was not indigenous; epidemics were imported by ship from the Caribbean. Prior to 1822, yellow fever attacked cities as far north as Boston, but after 1822 it was restricted to the south. Port cities were the primary targets, but the disease occasionally spread up the Mississippi River system in the 1800s. New Orleans, Mobile, Savannah, and Charleston were major targets; Memphis suffered terribly in 1878. Yellow fever epidemics caused terror, economic disruption, and some 100,000-150,000 deaths. Recent white immigrants to southern port cities were the most vulnerable; local whites and blacks enjoyed considerable resistance. PMID- 1604378 TI - Shades of blue: the negotiation of limited codes by medical residents. AB - One of the most difficult decisions facing physicians in contemporary medical practice is whether to initiate or withhold cardiopulmonary resuscitation (CPR) for patients who are critically ill. Because of the problems surrounding these decisions, hospital guidelines have recently been developed for the appropriate use of do-not-resuscitate (DNR) orders. Despite the establishment of these guidelines, problems with the application of DNR orders remain. This study examines one strategy used by internal medicine resident physicians to cope with the problematic nature of decisions regarding resuscitation--the use of partial or slow resuscitation attempts, known as 'limited codes.' It analyzes how these code efforts play a role within the context of resident work by enabling residents to circumvent ethical and practical dilemmas created by the circumstances of their clinical practice. PMID- 1604379 TI - Maternal education in relation to early and late child health outcomes: findings from a Brazilian cohort study. AB - In a population-based cohort of approximately 6000 Brazilian children, the associations between maternal education and a number of child health outcomes were studied while controlling for potentially confounding variables such as family income and education of the husband. In the crude analyses, maternal education was associated with perinatal and infant mortality, hospital admissions in the first 20 months of life and the three nutritional indicators (length-for age, weight-for-age and weight-for-length) at mean age 20 months. After adjustment for confounding, the apparent associations with outcomes in early infancy--birthweight and perinatal mortality--were no longer present, while that with infant mortality persisted despite being reduced. Strong associations remained with later outcomes including hospital admissions, length-for-age and weight-for-age at mean age 20 months. Among infants born to women with little or no schooling, deaths due to diarrhoea, pneumonia and other infectious diseases were particularly common. These findings support the hypothesis that maternal education has an effect on child health which is partly independent from that of other socioeconomic factors; they also suggest that maternal care is more important than the biological characteristics of the mothers since stronger effects were observed for the late (postneonatal mortality, hospital admissions and nutritional status) than for the early (birthweight, perinatal mortality) outcomes. PMID- 1604380 TI - Gender, marital status and the social control of health behavior. AB - Mortality rates are lower for married individuals than they are for unmarried individuals, and marriage seems to be even more beneficial to men than women in this regard. A theoretical model of social integration and social control is developed to explain why this may occur. Drawing from this model, I hypothesize that marriage may be beneficial to health because many spouses monitor and attempt to control their spouse's health behaviors. Furthermore, the provision, receipt, and consequences of these social control efforts may vary for men and women. These hypotheses are considered with analysis of a national panel survey conducted in 1986 (N = 3617) and 1989 (N = 2867). Results show that: (1) marriage is associated with receipt of substantially more efforts to control health for men than women, (2) those who attempt to control the health of others are more likely to be female than male, (3) there is some support for the social control and health behavior hypothesis among the married, and (4) the transition from married to unmarried status is associated with an increase in negative health behavior while the transition from unmarried to married status seems to have little effect on health behavior. A theoretical explanation is developed to explain these marital status differences. PMID- 1604381 TI - A comparison of social support variables between women who intend to breast or bottle feed. AB - Social support has been identified as an important element for encouragement and success of lactation. The sources, types and amounts of perceived social support were determined for women during their third trimester of pregnancy and at four weeks of postpartum breastfeeding. Differences in social support were reported for women who stated an intention to breastfeed and those who planned to bottle feed. The tangible, emotional and informational functions of social support were measured as aggregate values across support sources. Tangible and emotional support were not significantly different between intended breast or bottle feeders. However, informational support was higher for women who intended to breastfeed compared to those who intended to bottle feed. Mean scores were then analyzed for specific individuals who might provide support. The baby's father was a more important source of tangible support for intended breastfeeders. Intended breastfeeders also indicated they received more emotional and informational support from the baby's father and prenatal classes. Tangible, emotional and information support did not change pre- and postnatally for women who breastfed. However, certain sources did provide more support postnatally. Finally, predictors such as level of education, a belief that breastfeeding was better for health and emotional closeness, fewer children, moderate tangible and emotional support and more informational support were identified for women who intended to breastfeed. PMID- 1604382 TI - Correlates of hysterectomy in Australia. AB - With around one in five women undergoing hysterectomy by the age of 50, the prevalence of hysterectomy in Australia is greater than in Europe but less than in the United States. In this paper, data from a nationally representative sample survey of 2547 Australian women aged 20-59 years are employed to identify correlates of hysterectomy and tubal sterilization over the last 30 years. Physiological, socio-economic and supply-side factors all influence the propensity to undergo hysterectomy, and a comparison with the correlates of tubal sterilization reveals parallels and contrasts between the determinants of the two operations. Age and parity are important predictors of hysterectomy. In addition, use of oral contraceptives for at least five years reduces the risk of hysterectomy, as do tubal sterilization, tertiary education and birthplace in Southern Europe. Conversely, risk increases after experiencing side effects with the IUD or repeated foetal losses, or after bearing a third child before the age of 25. PMID- 1604383 TI - AIDS: the widening circle. PMID- 1604384 TI - Comparison of AIDS in women in rural and urban Georgia. AB - Through 1990, 308 cases of AIDS had been reported in female residents of Georgia (aged 13 years and older); 77 (25%) were white and 228 (75%) black. The mean age of the white women (43.8 years) was greater than that of the black women (34.5 years). One hundred sixty-six women were from Atlanta (metro Atl), the major metropolitan center in Georgia, and 142 (46%) from other regions of the state (other areas). Blacks represented 74% and 76% of all cases in women in metro Atl and other areas respectively. Of the 308 cases, 178 (58%) were related to intravenous (IV) drug use (99 metro Atl, 79 other areas), including 104 (58%) women who were IV drug users and 74 who were sexual partners of IV drug users. These proportions were similar in the two regions. Among cases related to IV drug use, 85 (86%) women in metro Atl and 69 (87%) women elsewhere in the state were black. The cumulative rate of AIDS in women in metro Atl (14.4/100,000) was twice that of women in the rest of the state (6.7/100,000). The rate for AIDS cases related to IV drug use in black women (27.8/100,000 population) was 19 times that in white women (1.5/100,000). The median survival of all women was significantly greater in metro Atl than in other areas (400 and 296 days respectively), with a difference also in those reported only with Pneumocystis carinii pneumonia (466 and 373 days respectively). PMID- 1604385 TI - Summertime respiratory syncytial virus infection: epidemiology and clinical manifestations. AB - Respiratory syncytial virus (RSV) is a common serious pathogen known to produce annual winter epidemics in young children. A 2-year study of children with significant respiratory disease during the summer revealed a 21% incidence of RSV infection. Respiratory secretions collected from ill children in the LSUMC outpatient clinics, from children seen by private physicians, and from children hospitalized with respiratory tract disease were assayed for RSV antigens. Approximately 39% of those surveyed in 1987 and 13% of those studied in 1988 were positive. As this prevalence was significant, we compared RSV-induced disease in 20 patients hospitalized in summer and 20 hospitalized in winter (1989). The patients were matched by age, weight, sex, and race. Comparisons included subjective severity of disease, presenting symptoms, physical findings, chest roentgenograms, treatment, and average length of hospital stay. No significant differences in disease severity and/or clinical presentation were found. Our findings show that RSV induces disease in the summertime more frequently than generally recognized, and severe disease requiring hospitalization is not infrequent. Physicians should consider RSV in children with serious respiratory disease throughout the year. PMID- 1604386 TI - Tuberculosis in the 1990's: resurgence, regimens, and resources. AB - Physicians in the United States must maintain vigilance for the 25,000 annual new cases of tuberculosis, concentrated in the elderly, in immigrants, in migrant and minority populations, and in immunosuppressed patients. Tuberculosis rates in the South remain above the national average. Physicians diagnosing tuberculosis may also treat the disease, working with health departments, which can assist with drugs, follow-up tests, and contact investigation. Powerful short-course regimens have been standard treatments since 1986. The preferred combination is isoniazid, rifampin, and pyrazinamide daily for 2 months, followed by isoniazid and rifampin for 4 more months. A 9-month regimen of isoniazid and rifampin is equally effective. Supplementation or extension of these regimens is mandatory when drug resistance or immunosuppression, respectively, is likely. Isoniazid prophylaxis for 6 to 12 months continues to be a vital but often neglected preventive measure for those infected with Mycobacterium tuberculosis, but without active disease. PMID- 1604388 TI - Heart disease, cancer, and stroke in Maryland. AB - Maryland has higher mortality rates from heart disease, cancer, and stroke (HCS) than the United States as a whole. More than 50% of deaths from HCS are premature, occurring before age 75. The health care and indirect costs from these three diseases total approximately $4.4 billion annually, placing a major economic burden on the state. A large body of scientific literature has shown the potential for the prevention of HCS. Currently, Maryland, like virtually all states, lacks the type of systematic, well-coordinated, comprehensive intervention campaign needed to lower morbidity, mortality, and health care costs from these three diseases. Such a campaign has now been planned by the University of Maryland at Baltimore. Similar campaigns are needed throughout much of the United States. PMID- 1604387 TI - Screening for hepatitis B among pregnant patients in a rural population. AB - From February 1988 to April 1990, we collected blood for hepatitis B surface antigen (HBsAg) from all women coming to the Texas Tech University Health Science Center in Lubbock for prenatal care. These patients were from rural western Texas and eastern New Mexico. They were also screened for hepatitis B risk factors, as outlined by the Centers for Disease Control. We reviewed the prenatal records of all HBsAg-positive women. Six of 4452 women (0.13%) had a positive HBsAg test. Four of the six women had identifiable risk factors and two did not; two were non Hispanic caucasian (Anglo), two were Hispanic, and two were black. Anglos comprised 49.5% of the rural population, Hispanics 34.9%, blacks 12.8%, and Asians 2.8%. No Asian women were positive for HBsAg. The prevalence of HBsAg positivity was lower in this rural population than in previously reported urban populations. While the prevalence in the studied blacks and Hispanics was similar to that in previous reports, the prevalence in the rural Anglos was lower. PMID- 1604389 TI - Development of the Virginia Congenital Anomalies Reporting and Education System (VaCARES): two pilot projects. AB - In 1986 legislation established the Virginia Congenital Anomalies Reporting and Education System (VaCARES). The system has three goals: to collect data that can be used to evaluate possible causes of congenital anomalies, to improve diagnosis and treatment, and to let parents and physicians know what resources are available to aid children born with anomalies. All children (from birth to age 2) with congenital anomalies admitted to Virginia hospitals after January 1, 1987, are being reported to VaCARES; VaCARES then contacts their families and physicians. Before the system was implemented statewide, its procedures were thoroughly tested through two pilot projects in selected hospitals. During the pilots, it was concluded that birth certificates alone are inadequate for case ascertainment. According to hospital reports, the incidence of all congenital anomalies during Pilot II was 562 out of 10,034 births (5.6%); birth certificates showed an incidence of only 83 out of 10,034 births (0.8%). During Pilot I, 3,466 (73.8%) of the diagnoses reported were perinatal conditions; the list of reportable conditions was accordingly altered, reducing perinatal conditions reported in Pilot II to 5 diagnoses (0.4%). It was estimated that there will be about 5000 to 7000 reports submitted to VaCARES each year. It was also shown that parents should be sent general rather than specific information about their child's birth defect and that quality control and close contact with reporting hospitals are essential to maintain the integrity of the registry data. PMID- 1604390 TI - Asbestos-related lung disease. AB - Asbestos is a versatile fibrous mineral that can cause lung disease and death. Asbestosis, benign pleural disease, lung cancer, and mesothelioma can all result from inhaling asbestos. The history of disease and exposure risks are discussed. The difficult assessment of risk and the long latency period for development of disease demand evaluation and regular surveillance of asbestos-exposed workers. PMID- 1604391 TI - New directions in asthma management. AB - Asthma affects people of all ages, and the mortality rate associated with the disease is increasing. The proper understanding of the pathogenic mechanisms, including airway inflammation and bronchoconstriction, can lead to a more logical treatment approach. Recognition of the important role of allergic triggers in influencing the sensitivity of the airways can help direct therapy toward prevention. Avoidance of irritants will help patients maintain normal airway function with fewer medications. Appropriate monitoring by the patient or the parent can help the medical team recognize worsening asthma before emergency treatment or hospitalization is required. The proper management of asthma necessitates understanding of the disease, medications, and goals by both the physician and the patient. PMID- 1604392 TI - American Indian medicine. PMID- 1604393 TI - Unto the least of these: the Howard Association and yellow fever. AB - Epidemics of yellow fever in mid-19th century America caused, in the port cities of the South, devastation and death almost unequalled in this country's history. In response to this horror, a benevolent organization of young men was formed to minister to the unfortunate victims through visitations, nursing care, supplies, and compassion. The group adopted the name Howard Association in honor of the British philanthropist and reformer, John Howard. This paper is an attempt to introduce this little-known society to 20th century readers by taking a brief look at some of the records of Howard Associations in several southern cities: New Orleans, Memphis, Norfolk, and Charleston. PMID- 1604394 TI - Pyogenic hepatic abscess and septic pulmonary emboli associated with Klebsiella ozaenae bacteremia. AB - We have reported a case of cryptogenic liver abscess with bacteremia and septic pulmonary emboli due to Klebsiella ozaenae. This organism has not previously been reported as a cause of intra-abdominal infection and this is only the eighth reported case of bacteremia. K ozaenae is generally considered an opportunist of low virulence and a respiratory tract colonizer implicated in ozena (atrophic rhinitis). More information is required to understand the epidemiology and pathogenicity of human disease caused by K ozaenae. PMID- 1604395 TI - Crohn's disease with associated bone marrow granulomas. PMID- 1604396 TI - Transmesosigmoid hernia during pregnancy. AB - We have presented a case of internal herniation of small bowel through the sigmoid mesocolon in a pregnant woman. In patients with symptoms suggestive of bowel obstruction, even without a history of previous abdominal surgery, internal hernia must be included in the differential diagnosis. PMID- 1604397 TI - The improbable intravesical foreign body. AB - Foreign objects in the urinary bladder can occasionally pose perplexing diagnostic problems, especially in the face of a seemingly incredible history. This case illustrates the importance of investigating such claims. Occasionally, alternate diagnostic methods such as fluoroscopy or ultrasonography may assist in noninvasive diagnosis and management. PMID- 1604398 TI - Simultaneous occurrence of postpartum hypopituitarism (Sheehan's syndrome) and transient resolving thyrotoxicosis due to postpartum painless thyroiditis. PMID- 1604399 TI - Polymorphous ventricular tachycardia in a newborn with the long QT interval. AB - We have reported a case of long QT syndrome in a neonate who had ventricular tachycardia 30 minutes after birth. On the third day, while being weaned from lidocaine, the patient had ventricular flutter and required cardioversion. Treatment with propranolol (5 mg/kg/day) maintained normal sinus rhythm. We believe this may be the first reported case of long QT syndrome and normal AV conduction in a neonate who had multiple episodes of ventricular tachycardia despite medical treatment. PMID- 1604400 TI - Traumatic false aneurysms of peripheral arteries in children. PMID- 1604401 TI - Giant leiomyoma of the small intestine with free perforation into the peritoneal cavity. AB - Leiomyomas involving the small bowel are rare benign tumors comprising 0.2% to 1.8% of all gastrointestinal tumors. We have presented a case with the rare complication of a free perforation between the tumor and the peritoneal cavity, causing an acute abdomen. PMID- 1604402 TI - Chondroblastoma. PMID- 1604403 TI - Deep venous thrombosis in umpires. AB - I have reported the case of an umpire who had deep venous thrombosis. Specialized clothing may have been an etiologic factor. PMID- 1604404 TI - Childhood sexual abuse and adult obesity. PMID- 1604405 TI - Other threats to health in the Persian Gulf region. PMID- 1604406 TI - Self-mutilation. PMID- 1604407 TI - [The digitalized sialo- and dacryocystogram]. PMID- 1604408 TI - [Perfusion characteristics of intrathoracic intestinal interpositions in i.a. DSA]. PMID- 1604409 TI - [The appearance of the joint split width in the x-ray picture following intertrochanteric displacement osteotomy of the hip]. PMID- 1604410 TI - [The general practitioner and general hospital in the follow-up of advanced tumors]. PMID- 1604411 TI - [Non-steroidal anti-inflammatory agent, phase I clinical trial with CN-100- single and repeated oral administration study]. AB - In vivo pharmacokinetics and safety of CN-100, a propionic acid derivative non steroidal anti-inflammatory drug (NSAID), were investigated in 12 healthy male volunteers with single oral administration at a dose of 150 or 300 mg, or repetitive oral administrations at a daily dose of 300 mg. The plasma concentration of CN-100 reached maximum approximately 1.5 hrs. after the administration and disappeared from the body with a half-life of about seven hrs. No cumulative effect was confirmed by the repetitive administration. The in vivo pharmacokinetics of CN-100 were not affected by a meal one hr. prior to the administration. In clinical examinations, slight elevations of GOT and GPT were observed in one case, and slight increase of number of leucocyte was observed in two cases but no other notable subjective symptoms or objective findings were found. Thus, the pharmacokinetic and safety studies of CN-100 concluded that the drug is evaluable in phase II test under thorough examination and control. PMID- 1604412 TI - [Detection of intracranial lesions of rheumatoid vasculitis with magnetic resonance imaging (MRI)]. AB - Vasculitis in malignant courses of rheumatoid arthritis is found in many systems, but rarely in the central nervous system. It has been reported that magnetic resonance imaging (MRI) is capable of depicting minute infarctions and/or lesions of demyelination more clearly than does X-ray computed tomography (CT). In the present study, we compared MRI and/or CT of the brain in 3 cases with rheumatoid vasculitis to gauge their relative usefulness for detecting cerebrovascular damages in such patients. In one case with focal neurological symptoms (case 1), MRI depicted lesions responsible for the symptoms more clearly than did CT. In the other two cases (cases 2 and 3), which had no neurological nor psychiatric symptoms, MRI detected multiple microinfarcts in each brain; CT revealed no such lesions. These results indicate that MRI may be more useful than CT to detect brain lesions in patients with rheumatoid vasculitis, and that patients with rheumatoid vasculitis who show no CNS symptoms may in fact still have cerebrovascular lesions. Further studies with MRI in more patients with rheumatoid vasculitis should establish the incidence of cerebrovascular involvement such patients; it is probably much higher than has been previously reported. PMID- 1604413 TI - [Studies on clinical subsets and severity of systemic lupus erythematosus based on a 1987 questionnaire conducted in Japan--clinical analysis of the outcome and treatments in clinical subsets]. AB - A 1987 questionnaire sponsored by the Health and Welfare Ministry concerning the clinical subsets and severity of systemic lupus erythematosus (SLE) was distributed to 93 medial facilities. A clinical analysis of the outcome and treatments was accomplished on one thousand six hundred and fourteen SLE patients fulfilling ARA criteria. The outcome was evaluated into 6 categories, namely; complete remission, incomplete remission, no change, gradual worsening, rapid worsening and unknown. Treatments included (1) anti-inflammatory drugs, (2) initial dose of prednisolone (PSL) below 29 mg/day, (3) initial dose of PSL from 30 to 59 mg/day, (4) initial dose of PSL above 60 mg/day, (5) pulse therapy, (6) immunosuppressants, (7) plasmapheresis, and (8) hemodialysis. Statistical significances were determined with ridit analysis. The severity of the disease for 1,614 SLE patients was evaluated by the judgement of each medical facility independently, separating it into 3 grades. As a result, 16.8% was evaluated as severe, 54.6% was evaluated as moderate, and 28.6% was evaluated as mild. Clinical subsets were divided into 3 categories according to the outcome; (1) those with high complete remission rates (serositis, convulsion, oral ulcers, unconsciousness, hemolytic anemia and so on), (2) those with high incomplete remission rates (lupus nephritis, digital gangrene, hypertension, peripheral neuropathy, erythema, Raynaud's phenomenon and so on), and (3) those with high rates of no change or worsening (aseptic bone necrosis, pulmonary hypertension, pneumonitis, chronic renal failure and so on). SLE patients with persistent proteinuria below 3.4 g/day, pulmonary hypertension, or pneumonitis treated with large doses of PSL such as an initial dose of PSL above 60 mg/day and/or pulse therapy had a significantly higher remission rate than those treated with small dosages of PSL. Hereafter, the establishment of modes of treatments for increasing the remission rates of intractable clinical subsets in highly desired. PMID- 1604414 TI - [The treatment of rheumatoid arthritis with low dose pulse methotrexate- comparative study with other disease modifying antirheumatic drugs]. AB - Low dose pulse methotrexate (MTX, 5-7.5mg/week) was administered to fifty one patients with severe and active rheumatoid arthritis (RA) who did not respond to the various disease modifying antirheumatic drugs (DMARDs). The follow-up period ranged from 2 to 30 months. As to efficacy rate and probability of patients continuing therapy, the results of MTX were compared with those of the other DMARDs (131 cases of bucillamine (BU), 163 of D-penicillamine (DP), 98 of salazopyrin (SASP), 126 of auranofin (AF), 55 of lobenzarit (CCA)). The patients treated with MTX showed remarkable improvement within 1 or 2 months in Lansbury's index items, CRP, immunoglobulin levels and rheumatoid factor values. But OKT4/8 ratio remained unchanged throughout the study period. As to the adverse reactions due to MTX an elevation of serum transaminase occurred most frequently (41.2%). MTX treatment was, however, tolerable to the most cases with its transient discontinuance or its dose reduction. The efficacy rate of MTX (71.4%) was the best among above mentioned DMARDs at the end of 6 months treatment. After treatment of 24 months, the probability of still taking MTX (70.1%) proved to be about the same with that of DP and better than that of BU, SASP, AF and CCA. In conclusion low dose pulse MTX turned out to be effective in the treatment of severe and active rheumatoid arthritis. PMID- 1604415 TI - [Clinical significance of anti-nucleolar antibodies detected by immunoprecipitation method in patients with systemic sclerosis]. AB - We have characterized a clinical significance of anti-U3RNP, anti-7-2RNP, anti RNA polymerase I and anti-PM-Scl antibody, autoantibodies to nucleolar proteins detected by immunoprecipitation method in patients with systemic sclerosis (SSc). In 248 patients with SSc, anti-U3RNP antibody was positive in 9 (3.6%), anti-7 2RNP antibody was positive in 7 (2.8%) and anti-RNA polymerase I antibody was positive in 3 (1.2%). But none of 248 patients was positive for anti-PM-Scl antibody. Anti-U3RNP antibody positive SSc patients showed significantly lower frequency of joint and lung involvements, compared with anti-U3RNP antibody negative SSc patients. Anti-7-2RNP antibody was found only in patients with limited scleroderma. The anti-7-2RNP antibody could be detected before appearance of skin thickening, so this indicate the usefulness of detecting anti-7-2RNP antibody in the early stage of SSc. Two of 3 anti-RNA polymerase I antibody positive patients were classified as diffuse scleroderma. All anti-RNA polymerase I antibody positive patients had high incidence of internal organ involvements including lung, heart and kidney, so two of these patients died of heart failure. These data showed the close clinical association of antigenic specificities of anti-nucleolar antibodies analysed by immunoprecipitation method, and indicated the usefulness of detecting these anti-nucleolar antibodies in subgrouping of patients with SSc. PMID- 1604416 TI - [Studies on clinical remission of rheumatoid arthritis]. AB - Clinical remission was observed in 19 out of 276 patients with rheumatoid arthritis. Remission rate was higher in male patients. In order to determine the clinical characteristics of remission cases, comparative study was performed. Although the time between initiation of treatment and clinical remission varied from case to case, the remission was related to early diagnosis and use of immunomodulating drug. No exacerbation was observed in our 19 patients with remission for the periods of 17 observation months. However, serial X-ray examination of hands disclosed that the erosive changes developed even after clinical remission. PMID- 1604417 TI - [A case of limited form of Wegener's granulomatosis associated with persistent high titer of serum antineutrophil cytoplasmic antibodies]. AB - A thirty-six year-old male was admitted to our hospital because of a two year history of orbital mass. He had experienced inflammatory tumor of right lung six years before admission. Both the lung tumor and orbital mass were revealed as chronic panarteritis with diffuse necrotizing lesions. He was treated with low dose prednisolone, but the orbital mass gradually enlarged. We detected fluorescent cytoplasmic pattern of antineutrophil cytoplasma antibodies (ANCA) by the indirect immunofluorescence method (IF). We ascertained this case to be a limited form of Wegener's granulomatosis (WG) by histopathological finding and positive ANCA. The value of ANCA, estimated by enzyme linked immunosorbent assay (ELISA) was rather higher than that of generalized form of WG in other reports. There was no reduction of the size of orbital mass and the value of ANCA despite strong immunosuppressive therapy. In this case, the value of ANCA didn't represented disease activity. The presence of histopathological findings such as those observed in the present patient, i.e., abnormally high ANCA levels not associated with disease severity or progression, which are not in accordance with those conventionally reported, was considered very interesting in terms of the prevailing beliefs concerning involvement of ANCA in the mechanism of onset of WG. PMID- 1604418 TI - [A case of systemic lupus erythematosus (SLE) developing pan-dysautonomia]. AB - A 43-year-old woman who had been diagnosed as primary Sjogren's syndrome since 1986 developed severe constipation, urinary retention, dizziness at standing and polyarthralgia in February, 1990. Laboratory tests revealed proteinuria, hypocomplementemia and high titer of anti-DNA antibody. Diagnosis of SLE was made and she was admitted to our hospital on April 2, 1990. Physical examination on admission showed that she also had asymmetric pupils, impairment of sweating, orthostatic hypotension, neurogenic bladder, gastro-intestinal dysmotility and the diminution of R-R interval variability during deep breathing on the electrocardiogram. These findings suggested that she had pan-dysautonomia but there were no signs of motor and sensory disturbance. Because other diseases such as diabetes mellitus and amyloidosis which induced dysautonomia could be ruled out, her pan-dysautonomia seemed to be due to SLE. After the treatment with steroid pulse therapy, most of her dysautonomia improved rapidly. However, some of the disturbance had persisted for a long time. Pan-dysautonomia has been rarely reported as a complication of SLE, and high dose of steroid therapy at the early stage should be considered. PMID- 1604419 TI - [Systemic lupus erythematosus associated with benign intracranial hypertension: a case report]. AB - A case of systemic lupus erythematosus (SLE) with benign intracranial hypertension (BIH) is reported. A 41-year-old male with a history of SLE starting in 1982 was admitted to our hospital in December 1989 because of headache and vertigo. Laboratory examinations on admission showed proteinuria, mild anemia, and positive antinuclear and anti-Sm antibodies. No abnormal findings except high pressure of 350 mmH2O were observed in his cerebrospinal fluid (CSF). Fundoscopic examinations showed marked bilateral papilledema and retinal bleeding. Brain CT, MRI and angiography revealed diffuse brain edema without space occupying lesion and cerebrovascular diseases. Because there were no diseases such as endocrinological disorders, severe anemia, and no history of the administration of drugs which might cause intracranial hypertension, the diagnosis of BIH was made. Subsequently, he was treated with intravenous methylprednisolone therapy and osmotic diuretics and his clinical symptoms and pressure of CSF gradually improved. The decrease of CSF adsorption was observed with RI cisternography in our case. Psychosis, seizures and meningitis are common CNS manifestations in SLE patients. But BIH is very rare and its cause is unclear. Only 17 cases of SLE with BIH have been reported. The pathogenesis and treatment of BIH in SLE patients were discussed in this paper. PMID- 1604420 TI - [Spontaneous remission of dermatomyositis which developed one month after normal delivery]. AB - A case of dermatomyositis which developed one month after normal delivery and subsided spontaneously was reported. A 29-year-old woman gave birth to a healthy child. One month later, she noticed muscular pain and weakness of the upper extremities. On admission, there were diffuse edema of upper eyelids with heliotrope rash. The reddish skin rashes were observed on the extensor surfaces of the PIP and MP joints of fingers. Erythrocyte sedimentation rate was 29 mm/hr. The lactic dehydrogenase (LDH), SGOT, CK levels were 470 (normal 150 to 320 IU/l), 43 (normal 6 to 25 IU/l) and 317 (normal 21 to 110 IU/l) respectively. Autoantibodies to nuclear and cytoplasmic antigens were negative. Rheumatoid factor and anti-DNA antibody were negative. Thyroid function was normal. An electromyogram (EMG) demonstrated small amplitude short-duration polyphasic motor unit potentials. The muscle biopsy specimen from left upper arm showed degenerating muscle fibers and infiltration of inflammatory cells surrounding blood vessels. The skin biopsy revealed the presence of edema and perivascular infiltration of lymphocytes. Based on these clinical features and results of various diagnostic tests, a diagnosis of dermatomyositis was established. After the admission, muscle strength has improved dramatically and the CK returned to normal level without specific drug therapy. She has since been seen as an out patient, and complete remission lasted for two years up to date. Review of the literature disclosed that 13 cases of PM/DM which developed during pregnancy or postpartum have been reported including the present case. Detailed analysis showed that these patients were characterized by mild muscular diseases, rare occurrence of internal organ involvements and good response to steroid therapy. As our case, a spontaneous remission was also observed. Although the mechanism involved in occurrence of inflammatory myositis associated with pregnancy or delivery are not clarified, these patient indicated a presence of subset of PM/DM which do not require intensive drug therapy. PMID- 1604421 TI - [Clinics and prognosis of collagen diseases in childhood]. PMID- 1604422 TI - Regional distribution and kinetics of haloperidol binding in human brain: a PET study with [18F]haloperidol. AB - The regional distribution and the kinetics of haloperidol uptake in human brain were examined using [18F]haloperidol and PET in 9 controls and 5 schizophrenics while on haloperidol medication and after haloperidol washout. The regional distribution of [18F]N-methylspiroperidol, a tracer for D2 receptors, was measured in 1 normal subject for comparison. The uptake of [18F]haloperidol in the whole brain in normals was high (6.6% of the injected dose at 2 hr), and regional distribution was much more extensive than could be accounted for by the distribution of dopamine D2 receptors. In normals, the cerebellum, basal ganglia, and thalamus showed a greater concentration than the cortex, and there was minimal clearance of 18F from the brain during the 10-hr period of the study. Medicated schizophrenics showed a total brain uptake of 4.0% and had a significant clearance of [18F]haloperidol from brain and a higher concentration of [18F]haloperidol in plasma. After withdrawal from medication, [18F]haloperidol clearance from brain became slower than while on medication. These results are discussed in terms of the pharmacokinetics of haloperidol in the human brain and its binding to dopamine D2 receptors and to sigma receptors. PMID- 1604423 TI - Within-subject sensitization of striatal dopamine release after a single injection of cocaine: an in vivo microdialysis study. AB - Repeated microdialysis measurements, conducted 1 week apart at the same tissue site, were used to investigate the changes in basal and cocaine-stimulated extracellular dopamine (DA) levels after a single prior exposure to either saline or cocaine. Dialysis probes were placed into rats previously implanted with guide cannulas and basal levels of dopamine (DA), and its metabolites (DOPAC and HVA) were estimated in 20-min fractions of the dialysate. Basal levels in the extracellular fluid (ECF), estimated from pre-implantation calibration of the probes, were 7.9 +/- 0.7 nM DA, 4.9 +/- 0.8 microM DOPAC, and 3.6 +/- 0.6 microM HVA. After a stable baseline was obtained saline (1 ml/kg, i.p.) or cocaine (20 mg/kg, i.p.) was injected. Saline produced no significant changes in any of the neurochemical markers. A cocaine injection produced a sixfold increase in DA, while DOPAC and HVA were unchanged. One week later the same procedure was repeated except this time both groups received cocaine. In rats that had received cocaine 1 week earlier, basal DA levels in the ECF were doubled, whereas they were unchanged in rats that received saline a week earlier. Furthermore, the dopamine release in response to acute cocaine during the second week was elevated in animals which had been previously exposed to cocaine. Rotation was also measured during both weeks and, while a tendency toward behavioral sensitization was observed, it did not reach significance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1604424 TI - Synaptic organization of the serotoninergic input to the superficial gray layer of the hamster's superior colliculus. AB - Immunocytochemistry with an antibody directed against a serotonin (5-HT)-bovine serum albumin (BSA) conjugate was combined with electron microscopy and serial section analysis to examine the synaptic organization of the serotoninergic projection to the stratum griseum superficiale (SGS) of the hamster's superior colliculus (SC). Most of the 5-HT-immunoreactive swellings in the hamster's SC did not make conventional synaptic contacts. Examination of 250 such swellings in single thin sections revealed only 11 synapses. Assessment of an additional 50 swellings followed through serial sections showed that only 6% (N = 3) of these varicosities made conventional synaptic contacts. All the synapses made by serotoninergic axons were with the dendrites of SC neurons. These results demonstrate that the inhibitory effects of 5-HT on SC neurons in hamster are mainly mediated by the nonsynaptic release of this indoleamine. PMID- 1604425 TI - Feedback inhibition of met-enkephalin release from the rat spinal cord in vivo. AB - The possible existence of a feedback control by endogenous opioids of the spinal release of met-enkephalin-like material was assessed in vivo, in halothane anesthetized rats whose intrathecal space was continuously perfused with an artificial cerebrospinal fluid supplemented with various opioid-related drugs. Both the intrathecal perfusion of the mu agonist D-Ala2-D-MePhe4-Gly-ol5 enkephalin (DAGO) (10 microM) and the delta agonist Tyr-D-Thr-Gly-Phe-Leu-Thr (DTLET) (10 microM) produced a significant inhibition of the spinal outflow of met-enkephalin-like material. The effect of DAGO, but not that of DTLET, could be prevented by naloxone (10 microM), and, conversely, the effect of DLTET, but not that of DAGO, was no longer observed in the presence of naltrindole (10 microM). Therefore naloxone and naltrindole acted as potent and selective mu and delta antagonists, respectively, when perfused at 10 microM in the intrathecal space of halothane-anesthetized rats. As expected from the lack of a tonic opioid control of spinal enkephalinergic neurones, neither naloxone nor naltrindole alone affected the spontaneous outflow of met-enkephalin-like material. However, naltrindole, but not naloxone, markedly increased the spinal overflow of met enkephalin-like material due to intrathecal administration of either porcine calcitonin (10 microM) or the peptidase inhibitors thiorphan (10 microM) plus bestatin (20 microM). These data suggest that delta, but not mu, receptors are involved in a phasic opioid inhibitory control of the release of met-enkephalin like material in the rat spinal cord.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1604426 TI - Dynamics of cytonuclear disequilibria in finite populations and comparison with a two-locus nuclear system. AB - We study the behavior of cytonuclear disequilibria in a finite monoecious population due to (1) random drift alone, (2) random drift and mutation, and (3) random drift and migration, using exact results on the RUZ (Random Union of Zygotes) model and diffusion approximations. We also show that the RUG (Random Union of Gametes) model is not suitable for a cytonuclear system. The study is also accompanied by a comparison with a two-locus nuclear system. We show that in a finite population of size N without mutation, the rate of decrease of the cytonuclear allelic disequilibrium is the same as that in the corresponding unlinked two-locus nuclear system. The principal rate of decrease of variance in allelic disequilibrium in a cytonuclear system is slightly faster than that in the corresponding nuclear system. However, the expected value of the variance in cytonuclear disequilibria is larger than that in a two-locus nuclear system for at least the first N generations. With mutation, the expected value of steady state variances of both systems are about the same; however, the normalized variance in linkage disequilibrium sigma 2d of the cytonuclear system is about twice as large as that for the corresponding nuclear system. For the migration process, two sets of steady state solutions are provided, one for the variables before migration and the other for the variables after migration. Diffusion approximations for both the principal rate of decay and steady state solutions in both systems are found to be satisfactory. A more accurate backward diffusion equation for a two-locus nuclear system is provided when the recombination fraction R is large. PMID- 1604427 TI - Survival of small populations under demographic stochasticity. AB - We estimate the mean time to extinction of small populations in an environment with constant carrying capacity but under stochastic demography. In particular, we investigate the interaction of stochastic variation in fecundity and sex ratio under several different schemes of density dependent population growth regimes. The methods used include Markov chain theory, Monte Carlo simulations, and numerical simulations based on Markov chain theory. We find a strongly enhanced extinction risk if stochasticity in sex ratio and fluctuating population size act simultaneously as compared to the case where each mechanism acts alone. The distribution of extinction times deviates slightly from a geometric one, in particular for short extinction times. We also find that whether maximization of intrinsic growth rate decreases the risk of extinction or not depends strongly on the population regulation mechanism. If the population growth regime reduces populations above the carrying capacity to a size below the carrying capacity for large r (overshooting) then the extinction risk increases if the growth rate deviates from an optimal r-value. PMID- 1604428 TI - Secondary theorem of natural selection in biocultural populations. AB - The "Secondary Theorem of Natural Selection," an extension of Fisher's fundamental theorem, states that the rate of change in the mean of an arbitrary character in response to selection is proportional to the additive genetic covariance between the character and fitness. Here I derive an expression for the change in the mean value of a trait subject to both genetic and cultural transmission. I start with the one-locus case under generalized mating and cultural transmission from parents to offspring, then proceed to the two-locus case. My results support previous work on the effects of nongenetic inheritance by showing that (i) cultural transmission introduces a timelag in the population response to selection; (ii) with cultural transmission the effects of selection persist even after selection is relaxed; and (iii) cultural transmission can either enhance or retard phenotypic evolution relative to that obtained under purely genetic transmission. PMID- 1604429 TI - Reflections of a reluctant clinical ethicist: ethics consultation and the collapse of critical distance. AB - The obvious appeal and growing momentum of clinical ethics in academic medical centers should not blind us to a potential danger: the collapse of critical distance. The very integration into the clinical milieu and the processes of clinical decision making, that clinical ethics claims as its greatest success, carries the seeds of a dilution of ethics' critical stance toward medicine and medical education. The purpose of this paper is to suggest how this might occur, and what potential contributions of ethics to medicine might be sacrificed as a result. Medical sociology will be used for comparison. Sociologists have found that they may function either as students and critics of established medical practices and educational philosophies, or as collaborative participants in them- but rarely both. It may be that professional ethics is most effective when it plays the role of 'stranger' rather than insider, and is continually able to question the most basic assumptions and values of the enterprise with which it is associated. As with medical sociology, ethics and humanities must ask to what extent their desire for acceptance in the clinic requires their acceptance of the clinic: specifically, acceptance of basic assumptions about optimal ways of organizing medical education, socializing physicians-in-training, providing care, and even of defining medical ethics itself. The paper concludes by recommending that ethics reassert its 'strangeness' in the medical milieu even as it assumes a more prominent role within the medical center. PMID- 1604430 TI - Which opinion should a clinical ethicist give: personal viewpoint or professional consensus? AB - When clinical ethicists are called upon to give a recommendation regarding patient care, they may be faced with a dilemma of their own. If their own personal opinion is not widely shared, the ethicist will have three options. These include: (1) giving their own opinion; (2) giving the widely shared opinion; and (3) giving both opinions, leaving the physician to select which opinion to accept. The intentions of this article are to evaluate strengths and weaknesses of these three alternatives and to suggest that ethics consultants recognize and deal with this issue. Two cases are presented to explore the limitations of each option. The author suggests that when the views of ethics consultants differ from the consensus view, the consultant should give the consensus view, their own dissenting view and the arguments in support of each position. PMID- 1604431 TI - Political and interpersonal aspects of ethics consultation. AB - Previous papers on ethics consultation in medicine have taken a positivistic approach and lack critical scrutiny of the psychosocial, political, and moral contexts in which consultations occur. This paper discusses some of the contextual factors that require more careful research. We need to know more about what prompts and inhibits consultation, especially what factors effectively prevent house officers and nonphysicians from requesting consultation despite perceived moral conflict in cases. The attitudes and institutional power of attending medical staff seem important, especially where innovative interventions raise ethical questions. Ethics consultants also need to address the thorny problems of the origin(s) of the consultant's authority, whistleblowing, conflicts of interest that affect the consultant, persistently poor communications in hospitals, systemic inequity in the availability or quality of services for some, and the standing of the consultant's recommendations, including their appearance in the patient's medical record. PMID- 1604432 TI - Do physicians make too much money? AB - The average net income of physicians in the USA is more than four times the average net income of people working in all domestic industries in the USA. When critics suggest that physicians make too much money, defenders typically appeal to the following four prominent principles of economic justice: Aristotle's Income Principle, the Free Market Principle, the Utilitarian Income Principle, and Rawls' Difference Principle. I shall show that no matter which of these four principles is assumed, the present high incomes of physicians cannot be defended. PMID- 1604433 TI - The design and use of the bioethics consultation form. AB - The emergence of the ethics consultation as a means to resolve moral crises in clinical medicine has revealed the need for a worksheet that would facilitate intake and analysis. The author developed the "Bioethics Consultation Form" as an attempt to remedy this need. The form is arranged in an outline format and is a useful asset to ethics committee discussions and record keeping. The first section covers basic intake data concerning the patient's medical and personal information, advance directives, and values, as well as the values of the physician and family. After the intake section is completed with the above data, the ethics consultant then turns to the analysis section. This second section allows for (1) the discussion of conflicting values, (2) the identification of priorities, and (3) the elucidation of ethical norms relevant to the case. The Bioethics Consultation Form was adopted by the Patient Care Advisory committee of the Franklin Square Hospital Center in Baltimore, Maryland in 1986. The methodology in the use of the form will be discussed. Further, the potential spectrum of consultative cases that can be analyzed using the form will be highlighted. PMID- 1604434 TI - Does the philosophy of medicine exist? AB - There has been a great deal of discussion, in this journal and others, about obstacles hindering the evolution of the philosophy of medicine. Such discussions presuppose that there is widespread agreement about what it is that constitutes the philosophy of medicine. Despite the fact that there is, and has been for decades, a great deal of literature, teaching and professional activity carried out explicitly in the name of the "philosophy of medicine", this is not enough to establish that consensus exists as to the definition of the field. And even if consensus can be obtained as to what constitutes the philosophy of medicine, this does not mean that it exists as a field. In order to constitute a field, an inquiry must be well-integrated with other cognate inquiries and disciplines, have an established canon of key books, textbooks, anthologies and articles, and a set of distinctive and defining problems. The philosophy of medicine as it currently exists fails to satisfy these criteria and, thus, fails to exist as a field of inquiry. The non-existence of the philosophy of medicine is unfortunate. Medicine and philosophy would both benefit from the development of the philosophy of medicine as a field. The philosophy of medicine is an essential foundation for bioethics, it should provide insights into some of the key problems of the philosophy of science such as the nature of explanation and theoretical evolution, and, ought help to shape the goals as well as the methods used in both experimentation and research in medicine and the health sciences. PMID- 1604435 TI - Philosophy of medicine--from a medical perspective. AB - In this commentary on the article by Arthur L. Caplan [1] the philosophy of medicine is viewed from a medical perspective. Philosophical studies have a long tradition in medicine, especially during periods of paradigmatic unrest, and they serve the same goal as other medical activities: the prevention and treatment of disease. The medical profession needs the help of professional philosophers in much the same way as it needs the cooperation of basic scientists. Philosophy of medicine may not deserve the status of a philosophical subspecialty or field, but is so closely linked to the main trends of contemporary medical thinking that it must be regarded as an emerging (or reemerging) medical subdiscipline. PMID- 1604436 TI - Dose-response aggregometry--contribution to the precise platelet function evaluation. AB - A method for the determination of blood platelet aggregability as the function of ADP concentration is described. Individual platelet aggregability was characterised by means of parameters of the sigmoidal relationship between the dose of the aggregating reagent and the aggregation curve amplitude. The method was applied to establish ADP-induced aggregability of various mammalian species. The aggregation curves of rabbit and rat platelets reached significantly lower maximum amplitudes than those of human and dog platelets. The eman concentration of ADP was significantly higher in dog platelets and the slope of the dose response curve was significantly steeper in rat platelets compared to the other species studied. Some of the causes of individual intra-species ADP-induced aggregation variability revealed by means of dose-response aggregometry are discussed. PMID- 1604437 TI - Activation of human factor VII by the prothrombin activator from the venom of Oxyuranus scutellatus (Taipan snake). AB - The crude venom of Oxyuranus scutellatus (Taipan snake) was found to cleave single-chain human factor VII to yield a two-chain molecule indistinguishable from authentic factor VIIa by SDS-polyacrylamide gel electrophoresis. A protease that activates factor VII was purified from this venom by a combination of gel permeation and ion-exchange chromatography. Characterization of the venom factor VII activator revealed its apparent identity with the Oxyuranus scutellatus prothrombin activator. The purified venom prothrombin activator was observed to activate factor VII by limited proteolysis in a reaction that was greatly potentiated by calcium and phospholipids (75% phosphatidyl choline/25% phosphatidylserine). Treatment of the venom protease with 0.8 M NaSCN weakly inhibited its ability to activate factor VII indicating that, in contrast to prothrombin activation, the factor Va-like component of this oligomeric enzyme complex was not essential for the activation of factor VII. PMID- 1604438 TI - A useful restriction analysis for the determination of human antithrombin III variants with mutations from Ala 382 to Ala 384. PMID- 1604439 TI - Defibrotide has antiischemic activity in perfused rabbit hearts, preventing tissue Ca++ overloading. AB - Defibrotide (D), a polydeoxyribonucleotide obtained from mammalian lungs, reduced the ischemic contracture due to low perfusion (0.2 ml/min) of the isovolumic left heart of the rabbit and abolished the irregularity of the rhythm of the heart, thereby restoring the cardiomechanical activity upon reperfusion (20 ml/min). D stimulated the release of PG-like material. Indomethacin infusion completely prevented both the antiischemic activity of D and its ability to increase the generation of prostaglandins in the rabbit heart. Measurement by atomic absorption spectroscopy of calcium content in ischemic heart tissue and its mitochondrial fraction indicated that the ischemic procedure significantly increased tissue calcium content in both. D, Prostacyclin (PGI2) and Nifedipine protected the heart from ischemic ventricular contracture and prevented accumulation of calcium in the heart. The effect of D on preventing Ca++ overload was completely abolished by indomethacin infusion. The results indicate that the beneficial effects of Defibrotide in experimental ischemia are primarily due to a release of Prostaglandin E2 (PGE2) and PGI2, which in turn may inhibit the detrimental effects of calcium overload in myocytes and mitochondria. PMID- 1604440 TI - Effects of exercise test on plasma markers of an activation of coagulation and/or fibrinolysis in patients with symptomatic or silent myocardial ischemia. AB - It has been suggested that unstable angina at rest, like acute myocardial infarction, might be associated with a thrombotic process. In order to study the hypothesis that myocardial ischemia during exercise could also be associated with an activation of blood coagulation and/or fibrinolysis, we investigated the presence of plasma markers of a prethrombotic or thrombotic state (thrombin antithrombin III complexes TAT, prothrombin fragment F1 + 2, and D-dimers DD) in 100 consecutive patients with confirmed or suspected coronary artery disease during ergometric test with myocardial thallium-201 scintigraphy. Symptoms and scintigrams allowed to define three groups of patients: those showing no ischemia (n = 79) and those with symptomatic (n = 8) or silent myocardial ischemia (n = 13). Before exercise, DD and TAT levels were not significantly different among the three groups. On the other hand, the F1 + 2 levels were slightly albeit significantly higher in the patients without ischemia than in the patients with symptomatic or silent ischemia. After exercise, no significant difference was found between the three groups. Exercise induced a significant and parallel increase in both the TAT and the F1 + 2 levels (but not of the DD levels) in the three groups. Thus, our study does not support the hypothesis that myocardial ischemia, silent or symptomatic, is associated with an activation of plasma coagulation and fibrinolysis that can be distinguished from the exercise-induced thrombin generation. PMID- 1604441 TI - In vitro platelets/endothelial cells interactions in presence of acetylsalicylic acid at various dosages. AB - Venous endothelium is able to release in vitro substances which modifies platelet aggregation. A vascular fragment incubated in Michaelis buffer (pH 7.30), aliquoted and tested on platelet-rich-plasma partially inhibits the aggregometry parameters. Addition of acetylsalicylic acid (ASA) at ultra low dose (0.1 nM final solution in the incubation tube) presents a reversed effect on this inhibition. To explain this phenomenon, 6-keto-PGF1 alpha and von Willebrand factor were dosed in the incubation media. After determination of an active level of 6-keto-PGF1 alpha (200 pg/100 microliters), 2 series were made: series 1 included the values below 200 pg/100 microliters incubation media, series 2, the values above 200 pg/100 microliters incubation media. When the vascular fragment was incubated as described above, the results of aggregometry ratio for series 1 were: test A (without ASA): 0.84 +/- 0.18, test B1 (with 0.1 nM of ASA): 0.87 +/- 0.13. For series 2, they became: test A: 0.75 +/- 0.27, test B1: 0.93 +/- 0.16. Control was always: 1.00 +/- 0.00. For the same groups, 6-keto-PGF1 alpha values were: for series 1, test A: 81 +/- 57, test B1: 81 +/- 60 pg/100 microliters incubation medium, for series 2, test A: 596 +/- 495, test B1: 383 +/- 263 pg/100 microliters incubation medium. Analyses were also performed with 2 high doses of ASA (B2: 10(5) nM and B3: 10(6) nM final solution) in the same experimental conditions. In these groups, aggregation parameters were decreased (0.86 +/- 0.14 for 10(5) nM, 0.84 +/- 0.15 for 10(6) nM) as well as 6-keto-PGF1 alpha production (189 +/- 199 for 10(5) nM, 152 +/- 182 for 10(6) nM). For these two last ASA treatments, comparison of the results in groups set up according to the sensitive 6-keto-PGF1 alpha value (200 pg/100 microliters solution) showed no modification. So it seems that a certain reactive state, specific of ultra low dose treatment is necessary for the vascular endothelium to be sensitive at such treatment. PMID- 1604442 TI - The role of essential vitamins in the development of thrombosis and hemorrhage- an experimental study. AB - To evaluate the action of essential vitamins on hemorrhage, coagulation and thrombosis, a multivitaminized solution was daily administered at three different doses for two weeks to male Wistar rats. Two experimental models were carried out: a venous thrombosis and an induced-hemorrhage model. Results indicate a low thrombogenic effect, a large and dose-dependent decrease of hemorrhage and no effect on coagulation. The observed effects on thrombosis and hemorrhage were not connected with an overdose of vitamins involving many secondary effects, since no blood viscosity parameters were modified. Three main hypotheses are envisaged to explain these results: a direct effect on platelet functions, an action on the leukocytic population, and a possible modification of the vessel wall response. However, further investigations are needed to specify the mechanisms involved. PMID- 1604443 TI - TFC-612, a prostaglandin E1 derivative, enhances fibrinolytic activity in rats. AB - TFC-612 inhibited thrombus formation on wire coils inserted into the lumen of the inferior vena cava of rats after 5 oral doses of 1.0 and 3.2 mg/kg and subcutaneous doses of 1.0 and 3.2 micrograms/rat/hr. This compound showed slight inhibition of platelet aggregation induced by collagen at 1.0 and 3.2 mg/kg (po) and significant inhibition at 10 mg/kg. TFC-612 had no effect on the plasma coagulation system at 3.2 mg/kg. Conversely, oral doses of 0.32-3.2 mg/kg dose- dependently enhanced fibrinolytic activity as measured by euglobulin clot lysis time and lysis area on fibrin plates by euglobulin fraction. TFC-612 did not enhance fibrinolytic activity in vitro. These results suggest that the enhancement of fibrinolytic activity by TFC-612, which may be due to an increase in tissue plasminogen activator release or reduction of plasminogen activator inhibitors release, contributes to its inhibition of thrombus formation. PMID- 1604444 TI - The effects of saturated fatty acids on endothelial cells. AB - The present study reports on the effects of myristic(14:0), palmitic(16:0) and stearic(18:0) acids separately and combined with linoleic(18:2n-6), arachidonic(20:4n-6) and eicosapentaenoic(20:5n-3) acids on cultured human endothelial cell monolayers(ECM). The cell viability determined by trypan blue exclusion study, the release of lactate dehydrogenase(LDH) and 6-keto-PGF1 alpha into the medium from ECM incubated with albumin bound fatty acids(FA) were measured. The cell viability was reduced and the release of LDH from ECM was enhanced by 18:0(0.2mM, ratio 1, 2 and 4) and 16:0(0.4mM, ratio 2), but not by 14:0, or the unsaturated FA. The reduced cell viability induced by 18:0 was completely inhibited by polyunsaturated FA, 18:2n-6, 20:4n-6 and 20:5n-3. The release of 6-keto-PGF1 alpha was increased by 18:0, but not by 14:0 and 16:0. All three saturated FA potentiated 6-keto-PGF1 alpha production induced by 20:4n-6. Combined with 18:2n-6 or 20:5n-3, they also stimulated 6-keto-PGF1 alpha production. This study indicates that the three main dietary SFA, 18:0, 16:0 and 14:0 do not have the same effects on ECM. The damaging effect on endothelial cells induced by 18:0 and 16:0 may be of significance for the thrombogenic effects related to these saturated fatty acids. PMID- 1604445 TI - Effects of ticlopidine on monoclonal anti-CD9 antibody-induced platelet aggregation and microparticle generation. AB - We analyzed the effects of ticlopidine on platelet aggregation and on microparticle (MP) formation when platelets were exposed to a monoclonal anti-CD9 antibody (NNKY1-19) in vitro. Even when NNKY1-19-induced platelet aggregation was completely inhibited by preincubation with anti-GPIIb/IIIa antibody or Arg-Gly Asp-Ser, or by using washed platelets from a Glanzmann's thrombasthenia patient, the formation of MP was still observed. Prostaglandin E1 and protein kinase C antagonists (H-7 and staurosporine) inhibited both NNKY1-19-induced aggregation and MP formation. Ticlopidine or aspirin plus apyrase scarcely affected NNKY1-19 induced platelet aggregation, except to prolong the lag time. However, ticlopidine significantly inhibited MP formation (p less than 0.01). These results suggest that ticlopidine inhibits NNKY1-19-induced MP formation by a different mechanism to that of the other antagonists, and that this mechanism is unrelated to the inhibition of platelet aggregation. PMID- 1604446 TI - [Aspects of meat inspection in the framework of a system of Integrated Quality Control for slaughtering pigs]. AB - This article evaluates different aspects of meat inspection that are important in an integrated quality control system for slaughter pigs. The meat inspection service registers post-mortem abnormalities. However, to achieve a reliable registration, it is necessary to be able to identify individual animals on the slaughter-line. The information about post-mortem abnormalities can be used by the meat inspection service. Percentages of abnormalities in a shipment of pigs were included in meat inspection indices. It was not possible to predict the percentages of abnormalities in shipment of pigs from individual pig suppliers, but it was possible to classify fattening herds according to the meat inspection index. Information about the pigs delivered from a fattening herd was provided in two ways: by delivering relevant information on a quality control card, and by preselecting (done by the pig supplier) pigs according to the presence or absence of abnormalities. With both methods it was possible to divide pigs into a group with and a group without post-mortem abnormalities. It is necessary that the information supplied is accurate. Information can be checked by screening a number of animals for drug residues (and zoonoses) at the slaughterhouse, and by checking the information registered by the pig supplier in logbooks kept on the farm. From a comparison of results obtained with a meat inspection method based on visual inspection (no incisions, no palpitation) of the carcass with those obtained with the regular meat inspection method, it can be concluded that many abnormalities are detected equally well with both methods. Some recommendations for further research are given. PMID- 1604447 TI - [Ascaris suum infection as a cause of clinical problems in cattle?]. AB - A sudden decrease in milk yield, increased respiratory rate and occasional coughing were observed in dairy cows on two farms in spring 1991. Pigs were also kept on these farms, and pastures grazed by the cattle had been fertilised with pig slurry. Laboratory investigations of some of the cattle showed eosinophilia and high ELISA titres of antibodies against Ascaris suum. On one farm the clinical symptoms disappeared after the animals had been treated with oxfendazole and on the other farm the symptoms disappeared spontaneously with time. PMID- 1604448 TI - [Therapy, prognosis in a vomiting male cocker spaniel]. PMID- 1604449 TI - [Blood, sweat and....]. PMID- 1604450 TI - [War-time memories (2)]. PMID- 1604451 TI - [Veterinary dentistry (5). Instruments for extractions in pets]. AB - The increasing dental care of companion animals requires good instruments. The instruments needed to perform extractions well are described in this article. Research into the use of the most appropriate (used in humans) instruments has led to the establishment of a set of instruments for use for simple and complicated extractions in dogs and cats. PMID- 1604452 TI - [Threshed English ryegrass (Lolium perenne) as a cause of ryegrass 'staggers' in stabled heifers]. PMID- 1604453 TI - [Vitamin A deficiency in the turtle]. PMID- 1604454 TI - [Government policy on biotechnology in animals. Minister of Agriculture, Nature Conservation and Fishery]. PMID- 1604455 TI - ['Cows with swollen anus and vulva'; a similar case in pigs]. PMID- 1604456 TI - [A suspected iron poisoning in fallow deer]. PMID- 1604458 TI - Improving the quality of service delivery in Nigeria. AB - This study evaluates the effect of a nurse training program in family planning counseling skills on the quality of service delivery at the clinic level, as well as its impact on client compliance with prearranged appointments. The study used a quasi-experimental design to compare certified nurses who received six weeks of family planning technical training with certified nurses who, in addition to the technical training course, received a three-day course in counseling skills. Data were collected through client exit interviews, expert observation, and inspection of medical record abstracts. Trained nurses performed better than their untrained counterparts in the quality-of-care areas investigated--interpersonal relations, information giving, counseling, and mechanisms for encouraging continuity. The likelihood that clients will attend follow-up visits was also found to improve when they were attended by trained professionals. Short-term counseling training can significantly improve the quality of care provided by family planning workers, as well as client compliance with follow-up appointments. PMID- 1604457 TI - Impact of social marketing on contraceptive prevalence and cost in Honduras. AB - In 1984, the Honduran Family Planning Association launched a contraceptive social marketing program by introducing the oral contraceptive, Perla. This report examines the impact of the program on overall oral contraceptive use, use by particular subgroups, source of supply, and costs. Although use of oral contraceptives increased only slightly over the period 1984-87 (from 12.7 percent to 13.4 percent among women in union aged 15-44), the social marketing program significantly increased its share of the oral contraceptive market (from 7 percent in 1984 to 15 percent in 1987, and from 20 percent to 40 percent of sales at pharmacies). For the Honduran Family Planning Association to have realized cost savings as a result of clients switching from community-based distribution programs and commercial supply sources to contraceptive social marketing programs, the association would have had to reallocate its resources. Instead, the number of distributors in the community-based distribution program increased, while the amount of couple-years of protection from oral contraceptives decreased. PMID- 1604459 TI - Premarital sexual activity and contraceptive use in Santiago, Chile. AB - The Santiago Young Adult Reproductive Health Survey was conducted in 1988 to examine the sexual behavior of and contraceptive use among young adults in Chile. The survey was based on multistage household probability samples of 865 women and 800 men aged 15-24 who were living in Santiago in 1988. Findings show that 35 percent of females and 65 percent of males had had premarital intercourse. Among those who had done so, the median age at first experience was 18.4 years for women and 16.4 years for men. Only 20 percent of females and 19 percent of males used contraceptives at first premarital intercourse. Use of contraceptives increased with age at the time of that event. Fertility data reveal that 70 percent of first births were premaritally conceived, and more than one-third of these were born prior to union. The high rates of premarital and unintended pregnancy among young women and the low prevalence of effective contraceptive use indicate a need for greater emphasis on sex education and family planning services directed at adolescents and unmarried young adults in Santiago. PMID- 1604460 TI - Paraguay 1990: results from the Demographic and Health Survey. PMID- 1604461 TI - The quality of family planning services in rural China. AB - This article provides a preliminary analysis of three aspects of service quality in four rural counties in China--the availability of contraceptive methods, information given to users, and provider knowledge about methods. Contraceptive choice and characteristics of contraceptive use by women in the study areas are also examined. The data are derived from a survey carried out by the authors during 1987, under the auspices of China's State Family Planning Commission. The survey was conducted in four rural counties located in Fujian and Heilongjiang provinces. A total of 318 married women of reproductive age were randomly selected and interviewed. All family planning service sites serving the women were visited and a sample of service providers was interviewed. No shortage of contraceptives existed in any of the counties, but variations in community wealth and local procurement practices have resulted in the acquisition of an IUD with high failure rates. Although providers believe they inform women about method choices and side effects, women were poorly informed about the methods they selected. Not all providers who insert IUDs and distribute pills were knowledgeable about contraindications and side effects of the methods. Ever-use of contraception was nearly 100 percent, but most women, especially in Heilongjiang, have only used one method: the IUD or sterilization. Improvements in quality, especially in method mix, providers' level of knowledge, and the quality and quantity of information provided to users will likely improve contraceptive continuation, client satisfaction, and women's health. PMID- 1604463 TI - Employment in family planning and women's status in Bangladesh. AB - This study investigates how employment in family planning affects the status of community workers. The focus is on three critical variables: prestige, professional status, and social influence. The data are derived from a focus group study conducted in 1987-88 in the Maternal and Child Health and Family Planning Project in Matlab, Bangladesh. Focus-group sessions were held with community workers, their husbands, community leaders, and community women. Results show that although community workers initially faced intense hostility in the community, they succeeded in maintaining the prestige that is traditionally accorded to women in their conservative, rural society. Moreover, they established themselves as valued health and family planning professionals in a social context where professional roles for women have been extremely circumscribed. Finally, they gained social influence by performing a range of functions in the community that exceed formally prescribed job responsibilities. The professional and social leadership roles that community workers now assume imply a degree of status that seemed inconceivable a decade ago. That such change could result from a well-designed and appropriately managed family planning project deserves careful attention. PMID- 1604462 TI - Impact of sustainability policies on sterilization services in Latin America. AB - The Association for Voluntary Surgical Contraception retrospectively examined the impact of funding decreases on access to sterilization services at 20 nongovernmental family planning clinics in Mexico, the Dominican Republic, and Brazil. Clinic staff were asked questions about client fees, caseloads, availability of comparable low-cost or free services nearby, cost-recovery activities, and the socioeconomic profile of clients before, during the time, and after subsidies were lowered or eliminated. Funding reductions were followed by decreased caseloads at 14 of the 20 sites studied. Of the six others, four experienced an increase in caseloads, one saw no perceptible change, and one experienced a decrease only as a result of management policy to cut the caseload to improve quality. The most common response to the decrease in funding (shared by 17 sites) was an increase in client fees. In all but three of the 17 clinics, the increase in fees was met with a decline in caseloads. Moreover, at nine of these 17 sites, the fee increase effected a change in client mix; anecdotal evidence suggests that more middle-income and fewer lower-income clients were using sterilization services. Four lessons can be drawn from this study: Donors need to plan funding phase-outs carefully, in conjunction with grantees; grantees need to assess the costs of the procedure realistically, and assign fees accordingly; management needs to seek alternative funding sources in lieu of, or in addition to, increasing fees; and caseloads can be increased and costs recovered by diversifying services. PMID- 1604464 TI - The emergence of medical malpractice in America. PMID- 1604465 TI - Revolt against quarantine: community responses to the 1916 polio epidemic, Oyster Bay, New York. PMID- 1604466 TI - A tale of pursuing health deception. PMID- 1604467 TI - James W. Kennedy, M.D., and the Joseph Price Memorial Hospital: recollections. PMID- 1604468 TI - An indescribable feeling of wretchedness: letters to Samuel Jackson on epilepsy. PMID- 1604469 TI - Chronic vascular rejection of the heart and the kidney--have rational treatment options emerged? PMID- 1604470 TI - Xenografts of rat islets into diabetic mice. An evaluation of new smaller capsules. AB - Healthy rat islets were encapsulated in alginate-polylysine-alginate capsules measuring 0.25-0.35 mm in diameter using a modified encapsulation technique. The encapsulated islets were transplanted intraperitoneally in nonimmunosuppressed streptozotocin-induced diabetic BALB/c mice. The diabetic condition of the experimental animals was reversed within two days following the transplantation and the animals remained normoglycemic for up to 308 days, with a mean xenograft survival of 219.8 +/- 46.2 days. Four and six months posttransplant the capsules were removed from two recipients. This resulted in regression to a hyperglycemic state. After a second transplant of encapsulated islets, the animals returned to normoglycemia. In control mice that received free unencapsulated islets, the xenografts remained functional for no more than 12 days. Our study clearly demonstrates that the encapsulation of islets in the new smaller capsules can effectively prolong xenograft survival without immunosuppression. PMID- 1604471 TI - Recovery and hypersecretion of insulin and reversal of insulin resistance after withdrawal of short-term cyclosporine treatment. AB - We have previously demonstrated decreased insulin release and insulin resistance in dogs treated with cyclosporine (20 mg/kg/day). In this study we examine the changes caused by a lower CsA dose and evaluate the reversal of these changes. Six animals were treated for 2 weeks with oral CsA (15 mg/kg/day), after which CsA was discontinued. Glucagon stimulation tests (GST) and euglycemic clamp studies (ECS) were used to evaluate changes in insulin release and insulin resistance. GST were performed before CsA, after 2 weeks of CsA, and 3, 9, and 15 days after discontinuing CsA. ECS were performed before CsA, after 2 weeks of CsA, and 2, 4, 8, and 14 days after discontinuing CsA. The mean serum CsA level after 2 weeks of treatment was 188 +/- 28 ng/ml. GST demonstrated decreased insulin release during CsA with recovery and hypersecretion after CsA withdrawal. ECS showed peripheral insulin resistance during CsA with a rapid recovery and a temporary increase in insulin sensitivity after CsA withdrawal. Comparisons were made with our previous study group given 20 mg/kg/day of CsA. In summary, CsA induces a dose-dependent impairment of glucose homeostasis due to inhibition of insulin release and development of peripheral insulin resistance. Withdrawal of short-term CsA at commonly used therapeutic doses results in reversal of and temporary overcompensation for these changes. CsA withdrawal after long-term treatment results in a slower normalization of the insulin response as compared with after short-term treatment. The hypersecretory reaction of the beta cell may be of help in further investigations of mechanisms of CsA- and FK506-induced inhibition of insulin release. PMID- 1604472 TI - Biliary interleukin 6 levels as indicators of hepatic allograft rejection in rats. AB - Interleukin 6 has recently been noted to be present during the rejection response to grafted organs. In this study, we investigated biliary and serum interleukin 6 levels following liver transplantation in rats. IL-6 levels in bile and serum of naive rats were below 0.6 U/ml and 0.5 +/- 0.2 U/ml (mean +/- SD), respectively. Both biliary and serum IL-6 levels showed high values (greater than 10.0 U/ml and greater than 1.6 U/ml, respectively) on the day after transplantation, which seemed to reflect the inflammatory status caused by the surgical stress. Later samplings showed that the kinetics of serum IL-6 differed among the animals without any definite feature related to graft rejection. In contrast, biliary IL 6 levels correlated well with the severity of the rejection response as determined histologically. Biliary IL-6 levels started to rise at the onset of the rejection response (6.6 +/- 0.6 U/ml), increased further with its progression (19.3 +/- 7.8 U/ml), and then finally fell in the terminal stage (less than 2.0 U/ml). Elevation of biliary IL-6 was observed at an early stage when abnormalities could be detected histologically but not in liver function tests and bile flow. Therefore, biliary IL-6 levels may be of value for the early diagnosis of rejection following liver transplantation. PMID- 1604473 TI - Evaluation of UW solution for preservation of small intestinal transplants in the rat. AB - Simple cold preservation was evaluated in the rat model of small intestinal transplantation. Lewis rats received a syngeneic heterotopic graft of the jejunum either immediately (SI) or after preservation for 24 hr in Euro-Collins (SPE24), for 48 hr in EC (SPE48), for 24 hr in University Wisconsin solution (SPW24), or for 48 hr in UW (SPW48). The survival rates of SI, SPE24, SPE48, SPW24, and SPW48 were 100%, 78%, 0%, 100%, and 33%, respectively. Physiologic and pharmacologic properties of the grafts and native intestine were evaluated in vitro between 8 and 12 days after transplantation. Smooth muscle in all specimens contracted in response to cholinergic agonists, phenylephrine, and substance P, and was relaxed by isoproterenol. Excitatory innervation was present in 100%, 100%, 100%, and 67% of SI, SPE24, SPW24, and SPW48, respectively, while inhibitory innervation in each group was 50%, 29%, 60%, and 0%. Thus, smooth muscle function was preserved in all groups, but neural activity was impaired by some of the storage conditions. Preservation was best in SPW24, which had physiologic responses similar to those of SI. The rat jejunum can, therefore, be preserved in good condition for up to 24 hr before transplantation using simple cold storage in UW solution. PMID- 1604474 TI - An examination of the effects of solutions containing histidine and lactobionate for heart, pancreas, and liver preservation in the rat. AB - Fifty-five rat pancreas transplants, 18 rat heart transplants, and 41 rat liver transplants were performed using standard UW solution, the new HL solution (HL I), or a modified HL solution (HL-II). Storage times of 18 hr were used in the heart preservation experiments, 24 hr in the liver preservation experiments, and 48 or 72 hr in the pancreas preservation experiments. HL-I solution was superior to both HL-II and UW solution for heart preservation (1-week graft survival rates of 100% [7/7], 0% [0/5], and 50% [3/6], respectively). HL-I and HL-II were superior to UW for 24 hr liver preservation (1-week graft survival rates of 78% [11/14], 80% [8/10], and 29% [5/17], respectively). In contrast, HL-II was superior to both HL-I and UW solutions for pancreas preservation following both 48-hr preservation and 72-hr preservation. Satisfactory graft function was achieved in 100% (7/7), 40% (6/15), and 44.4% (4/9) of pancreases transplanted after 48 hr using HL-II, HL-I, and UW solutions, respectively, and in 50% (4/8), 0% (0/8), and 0% (0/8) following 72-hr preservation. Histidine- and lactobionate containing solutions thus represent a further improvement in organ preservation by simple cold storage. PMID- 1604475 TI - Breakdown of hepatic tight junctions during reoxygenation injury. AB - We investigated whether reoxygenation following anoxia increased biliary permeability and whether or not allopurinol had a protective effect. Isolated rat livers were perfused for 30 min in a one-pass system with buffer equilibrated with 100% nitrogen after stabilization, and then for 60 min with the oxygenated buffer. Hepatic tight junction permeability was assessed by quantifying the early appearance in the bile of horseradish peroxidase (HRP) injected with the perfusate. This early peak represents paracellular passage of HRP, whereas a later second peak results from transcellular passage. In the control livers, 7% of the total HRP passage (93 +/- 50 pg/g liver) was paracellular and 93% was transcellular. After 30 min of reoxygenation following anoxia, however, 516 +/- 20 pg/g liver of HRP passed paracellularly. Addition of allopurinol (5 micrograms/ml) to the perfusate from the start of perfusion reduced paracellular passage of HRP to 219 +/- 49 pg/g liver after anoxia and reperfusion (P less than 0.01). Allopurinol also reduced the cumulative lactate dehydrogenase (LDH) release during the first 30 min of reoxygenation from 2.1 +/- 0.3 x 10(4) to 1.4 +/- 0.4 x 10(4) units/g liver (P less than 0.01). Reduction of the anoxic period from 30 min to 25 min significantly reduced the change in tight junction permeability and the extent of cellular injury: Paracellular passage of HRP was 336 +/- 20 pg/g and LDH release was 0.7 +/- 0.1 x 10(4) units/g liver, both significantly lower than those at 30 min (P less than 0.01). No significant difference in hepatic ATP levels after 60 min of reoxygenation was noted among the experimental groups, but all had lower levels than the control group. The protective effect of allopurinol suggests that the mechanism of biliary reoxygenation injury involves free radical generation. Susceptibility of tight junctions suggests a pattern of injury similar to that involved in anoxic damage of the vascular endothelium. PMID- 1604476 TI - Myocardial energy metabolism in asphyxiated canine hearts preserved for 24 hours. AB - Myocardial energy metabolism in asphyxiated cadaver hearts preserved in UW solution (UWS; group 1, n = 6) or modified Collins' solution (MCS; group 2, n = 6) was compared with that in cardioplegic arrested hearts immersed in ice-cold MCS with (group 3, n = 6) or without myoprotective drugs (group 4, n = 5). All hearts were stored for 24 hr. The hearts in groups 1 and 2 were pretreated with prostacyclin, verapamil, and propranolol; asphyxiated for 10 min, reversed by coronary perfusion with warm blood cardioplegia (WBCP); perfused with ice-cold crystalloid cardioplegia for 2 hr; excised and immersed in cold storage solution for 22 hr; and perfused again with WBCP before reperfusion. ATP contents were measured in biopsy specimens by HPLC. Myocardial ATP level decreased significantly from 23.7 +/- 1.7 to 15.9 +/- 2.5 mumol/g dry wt. (P less than 0.0001) by asphyxia, but recovered to within normal limits by WBCP in group 1. The ATP level again decreased to 15.8 +/- 2.4 mumol/g dry wt. during 24-hr storage, but finally rose to 22.4 +/- 3.5 mumol/g dry wt. by terminal WBCP. The ATP metabolism in group 2 was similar to that in group 1. The ATP content in group 4 was significantly lower than that in other groups (P less than 0.01) after 24-hr preservation. The study shows that damage to cadaver hearts can be reversed and the hearts maintained satisfactorily viable for 24 hr. PMID- 1604477 TI - Variable effects of steroid withdrawal on blood pressure reduction in cyclosporine-treated renal transplant recipients. AB - The effects of complete withdrawal of steroid therapy on blood pressure and other clinical variables were studied in 58 renal transplant recipients subsequently maintained on azathioprine and cyclosporine; 76% of the patients were hypertensive prior to withdrawal of steroids. Cessation of steroids was accompanied by a significant decrease in mean arterial blood pressure and by a reduction in the number of required antihypertensive medications; however, changes in blood pressure were variable among individual patients. Previously normotensive patients exhibited little further decline in blood pressure. Multivariate analysis of the entire cohort of patients showed that the reduction in blood pressure accompanying steroid withdrawal was directly related to the prior severity of hypertension and inversely related to the dose of cyclosporine. We conclude that steroids play an important role in the pathogenesis of posttransplant hypertension in the majority of renal transplant recipients. Withdrawal of steroids generally is accompanied by reduction in blood pressure, but the benefit is greatest in previously hypertensive patients receiving relatively low doses of cyclosporine. PMID- 1604478 TI - Analyzing the number of "rejection episodes" in renal transplant studies. AB - Transplantation has become the treatment of choice for many chronic and debilitating diseases. Generally, the primary endpoints in evaluating therapy are graft and patient survival time. However, an important secondary outcome is the number of "rejection episodes" experienced by study patients. This response has a distinctive statistical character. That is, it is a categorical variable since it assumes only a small number of integer values, but it is measured on a ratio level scale since the ratio of any two values is scientifically meaningful. Historical methods for analyzing this endpoint, for example, t tests, logistic regression and Kaplan-Meier analysis, have failed to take these characteristics into account. In this study, we investigated statistical procedures for analyzing the number of rejection episodes arising during the first three months posttransplant. Data compiled by the Multiple Organ Retrieval and Exchange (MORE) of the Province of Ontario were used for this purpose. It was found that assumptions underlying normal distributional techniques were not satisfied by these data. An alternative model based on Poisson regression models was considered and was shown to provide an adequate fit. PMID- 1604479 TI - Coronary venous intimal thickening in explanted cardiac allografts. Evidence demonstrating that transplant coronary artery disease is a manifestation of a diffuse allograft vasculopathy. AB - The accelerated coronary artery disease occurring in cardiac allografts is thought to be a form of chronic rejection directed against allogeneic vascular endothelium. If this hypothesis is correct, one would anticipate disease not only in the arteries but in venous structures as well. Accordingly, the degree of myointimal proliferation of both coronary arteries and coronary veins was assessed in 22 explanted or autopsied cardiac allografts by light microscopy. Other factors assessed included clinical cause of death/retransplantation, time posttransplantation, underlying cardiac disease, donor and recipient age, and ischemic time. Thirteen of the 22 hearts had either moderate or severe arterial myointimal thickening. Of these, 10 hearts had associated coronary venous thickening. Of the 9 remaining hearts with either mild or no arterial myointimal thickening, none had venous involvement. The overall correlation between the presence and degree of allograft coronary artery and allograft coronary vein thickening was high (r = 0.80, P = 0.0014). Of the other demographic factors investigated, only length of time posttransplant had a weak correlation with arterial or venous myointimal thickening (r = 0.46, P = 0.045 and r = 0.48, P = 0.039, respectively. These data demonstrate that the usually termed "accelerated transplant atherosclerosis" in the cardiac allograft is a true vasculopathy and involves both the arterial and venous systems. PMID- 1604480 TI - The prevalence, course, and characteristics of chronic anemia after heart and lung transplantation. AB - A retrospective study of the 99 surviving heart and lung transplant (HLT) recipients at one center showed that 31% had significant anemia (hemoglobin less than 100g/L) six months after transplantation. Chronic anemia persisted in 18% of HLT recipients two years posttransplantation. A similar study of 100 heart transplant recipients showed no unexplained anemic patients. The prevalence of anemia after HLT was unrelated to the original diagnosis, immunosuppression, or acute rejection. All HLT recipients appeared to be unduly sensitive to the myelosuppressive effects of azathioprine. Detailed studies in 16 representative patients showed a normochromic, anisocytotic anemia with normal reticulocyte counts, B12 and folate levels, and haptoglobin levels and appropriate erythropoietin levels--but increased ESRs, low/normal iron levels and low/normal total iron binding capacity, normal or raised ferritin levels, and autoantibodies in 4 (25%). Bone marrow aspirates in 10 patients showed dyshemopoiesis out of proportion to the degree of anemia and colonies of activated lymphoid cells. The cause for this anemia appears to be a combination of anemia of chronic disease and dyshemopoiesis, both of uncertain etiology. PMID- 1604481 TI - Diminished anticoagulant and fibrinolytic activity following liver transplantation. AB - This study analyzed the coagulation changes in twenty patients after orthotopic liver transplantation. The procoagulant, anticoagulant, and fibrinolytic systems were studied during the first two postoperative weeks. Within the first postoperative day all extrinsic and intrinsic pathway factors became normal except factors IX, VII, and X, which recovered within the next 24 hr. Of interest are the changes in factor VIII, which reached a high concentration with an increase in its antigenic fraction during the study. However, coagulation inhibitors showed a different pattern. In fact, antithrombin III (AT-III) and protein C (PC) needed from 7 to 14 days to reach normal values. Total protein S (TPS) and free protein S (FPS) did not recover until day 7, whereas heparin cofactor II (HC-II) remained at subnormal levels throughout the study. Thrombin antithrombin III complex (TAT) values were strikingly elevated in the immediate postoperative period. Fibrinolysis parameters showed plasminogen (PL) levels in the normal range until day 4. Antiplasmin (AP) followed a curve parallel to that of plasminogen but its levels were higher during this observation period. Similarly the initial elevation in plasminogen activator inhibitor 1 endothelial type (PAI-1) levels remained high until days 4 and 7. In summary, it can be concluded that during the postoperative phase after OLT a hypercoagulable state is developed as a result of diminished anticoagulant and fibrinolytic activity. This coagulation might be a nontechnical factor contributing to the thrombotic vascular complications of some liver recipients. PMID- 1604482 TI - Prostacyclin accumulation during orthotopic liver transplantation in man. AB - Significant hypotension commonly occurs upon reperfusion of the donor liver. In this study we tried to determine if there is accumulation of prostacyclin in the portal system. Blood samples for prostacyclin in twelve patients undergoing orthotopic liver transplantation were studied. Samples were collected at the beginning and end of portal vein anastomosis. Hemodynamic measurements were determined 1 min before and 3 min after portal revascularization. The results show an increase of prostacyclin from 524 +/- 134 pg/ml (n less than 72 pg/ml) to 1132 +/- 264 pg/ml. Eight patients had a decrease in systolic blood pressure from 98 +/- 5 mmHg to 61 +/- mmHg with concomitant significant increase in cardiac output (6.0) from 6.9 +/- 0.7 to 9.9 +/- 1.05 L/mm and significant decrease in systemic vascular resistance (SVR) from 724 +/- 130 dynes/sec/cm to 309 +/- 98. In conclusion, 60% of patients undergoing OLT accumulate prostacyclin in the portal vein, which could be one of the causes of hypotension seen at reperfusion of the donor liver. PMID- 1604483 TI - Differential response of kidney and pancreas rejection to cyclosporine immunosuppression. AB - Immunological interferences between kidney and pancreas transplants were investigated in a genetically defined rat model of combined kidney and pancreas transplantation. Kidney and whole-pancreas grafts were transplanted microsurgically either as individual grafts or in a combined technique. Whole pancreas grafts were grafted into streptozotocin diabetic recipients (55 mg/kg bodyweight i.v.) three days after induction of diabetes. The exocrine secretion was suppressed by duct ligation. Rejection of the grafts was defined by recurrence of diabetes in pancreas-grafted recipients and renal failure after kidney transplantation. There were marked differences in the efficacy of identical short-term cyclosporine immunosuppression (15 mg/kg intramuscularly for 14 days): DA kidneys survived indefinitely in LEW rats (MST greater than 100 days), while DA pancreas allografts underwent prolonged but not permanent survival (P less than 0.01) either as individual grafts (MST 27.3 +/- 1,9 days) or when transplanted simultaneously together with the kidney (44 +/- 16 days) (P less than 0.01). LEW rats carrying a DA kidney for 100 days also rejected a subsequent donor-specific pancreas transplant within 30 days. The histological alterations in the kidney were more pronounced than after cyclosporine-induced DA kidney long-term survival alone. By contrast to the rejecting subsequently transferred pancreas, a metachronous second DA kidney was permanently accepted (greater than 100 days) without further immunosuppression after removal of the first graft, while unrelated LEW. 1U kidneys were acutely rejected. In summary, the results indicate that there are not only quantitative differences of kidney and pancreas allograft survival but also differences concerning the state of immunological unresponsiveness induced by identical cyclosporine immunosuppression. While CsA induces donor-specific immunological unresponsiveness after kidney transplantation, pancreas transplants are all eventually rejected after some differential prolongation of survival. Further investigations on the effects of different MHC and minor alloantigens may provide more insight into the complex immunological situation of individual and combined kidney and pancreas transplantation. PMID- 1604484 TI - Pharmacodynamic studies of cyclosporine in marrow transplant recipients. A comparison of three assay methods. AB - We investigated the correlation between trough cyclosporine concentration in plasma measured by polyclonal fluorescence polarization immunoassay (FPIA) and polyclonal radioimmunoassay (RIA) or in whole blood measured by high-performance liquid chromatography (HPLC) and the risk of renal dysfunction or acute graft versus-host disease in 29 patients undergoing allogeneic bone marrow transplantation for leukemia. The FPIA and RIA values were highly correlated (r = 0.93) and on the average CsA concentrations measured by FPIA were 1.56 times higher than those measured by RIA. Ten patients developed renal dysfunction and 10 developed grades II-IV acute GVHD. Although univariate analysis showed that plasma CsA concentrations measured by either FPIA or RIA were significantly correlated with renal dysfunction, the association was stronger with FPIA. Plasma CsA concentrations measured by FPIA but not RIA remained a significant risk factor for renal dysfunction in a multivariate relative risk model. Amphotericin therapy was significantly associated with renal dysfunction in the univariate analysis but not in the multivariate analysis. No significant associations were found between whole blood CsA or CsA M1 concentration, patients' age, gender, or CsA dose and the risk of renal dysfunction. None of the covariates analyzed significantly correlated with the development of acute GVHD. These data suggest that plasma CsA concentrations measured by nonspecific assays may more accurately correlate with renal dysfunction than whole-blood CsA concentrations measured by HPLC in marrow transplant recipients. PMID- 1604485 TI - Blocking of mononuclear cell accumulation, cytokine production, and endothelial activation within rat cardiac allografts by CD4 monoclonal antibody therapy. AB - CD4 monoclonal antibody therapy prolongs allograft survival in a variety of experimental models and is currently undergoing clinical trials, though surprisingly little is known about the effects of CD4 mAb therapy on intragraft effector mechanisms that mediate rejection. We previously reported the significantly improved survival of (LEWxBN)F1 cardiac allografts in LEW rats treated for 10 days with the new CD4 mAb, BWH-4, at a dose of 700 micrograms/day, i.v., starting at the time of engraftment. Thus, CD4-treated rats showed prolongation of allograft survival to a median of 37 days (range 22 to greater than 100 days) post-Tx, compared with rejection at 7 days in untreated controls. We now report the results of detailed immunohistologic studies of allografts collected from these rats. Comparison of acutely rejecting allografts in untreated rats with well-functioning allografts collected at day 7 post-Tx from CD4-treated rats showed that CD4 mAb: (1) significantly reduced mononuclear cell infiltration, interstitial edema, hemorrhage formation and vascular and extravascular thrombosis; (2) inhibited mononuclear cell induction of receptors for IL-2 and transferrin, and upregulation of class II antigens and ICAM-1 on leukocytes and endothelial cells; (3) suppressed intragraft mononuclear cell and/or endothelial production of the cytokines IL-1, IL-2, IL-6, IFN-gamma, and TNF; and (4) blocked upregulation of endothelial tissue factor and downregulation of thrombomodulin, and consequently inhibited fibrin deposition. Studies of allografts from CD4-treated rats collected at day 30 post-Tx, prior to clinical rejection, showed a resurgence of CD4+ cells within allografts and a dense cellular immune response. We conclude that short-term CD4 mAb therapy has potent and extensive inhibitory effects on cytokine-related mononuclear cell and endothelial activation in vivo, blocking multiple afferent and efferent steps of the alloresponse. PMID- 1604486 TI - Detection of donor-reactive alloantibody in the early posttransplant period. Elimination of therapeutic ALG as a complicating factor. AB - We have developed an immunoabsorbent reagent that can differentially remove ALG from human serum samples in vitro--i.e., goat antihorse IgG covalently linked to Sepharose beads. When used according to protocol, this immunoabsorbent can effectively remove up to 0.78 mg/ml of ALG from human serum mixtures. To demonstrate that immunoabsorption is selective, an HLA-B7-specific alloserum was mixed with a known amount of ALG and absorbed with antibody-conjugated Sepharose beads. The addition of ALG to the serum sample caused high degrees of nonspecific lympholysis in standard microcytotoxicity assays. When this serum/ALG mixture was immunoabsorbed detectable ALG activity was lost but the original HLA alloantibody titer (1:2) against specific target lymphocytes was retained. PMID- 1604487 TI - Development and characterization of monoclonal antibodies to lymphocyte cell surface antigens of the rhesus monkey. AB - Three monoclonal antibodies directed against rhesus lymphocyte cell surface antigens are described. A pan-T mAb, T64, and a T suppressor mAb, T35, showed phenotypic and functional specificity for both human and rhesus cells. In contrast, a third mAb, N42, identifying natural killer cells in rhesus peripheral blood leukocytes, was not crossreactive with the corresponding homologous human cells. N42 reacted with the same cells identified by Leu 11a and Leu 11b in rhesus PBL and in a functional assay decreased NK activity by 80%. N42 precipitated a 50KD protein from rhesus PBL lysates and was reactive with the Fc receptor domain of the NK cell. The T-S functional activity of cells reactive with mAb T35 was demonstrated in a pokeweed-mitogen-driven system for Ig synthesis: removal of the T35 positive cells by complement-mediated lysis led to an enhanced production of Ig by rhesus PBL, and the addition of T35 positive cells to a culture of T helper and B cells resulted in a reduction of this response. T35 was determined to be an IgG2a immunoglobulin and precipitated a 34KD protein from rhesus cell lysates. An IgM immunoglobulin, mAb T64 delineated all T lymphocytes, inhibited E-rosette formation, interfered with the proliferation of cells stimulated with mitogens, and precipitated a 52KD membrane protein. The potential utilization of these mAbs in vivo for organ or tissue transplantation in the rhesus monkey is discussed. PMID- 1604488 TI - The effectiveness of pretreatment with soluble or membrane-bound donor class I major histocompatibility complex antigens in the induction of unresponsiveness to a subsequent rat renal allograft. AB - We have examined the ability of two physical forms of RT1.A class I molecules to induce immunologic unresponsiveness to renal allografts in the rat. Both preparations of class I MHC antigen were derived from rat liver. Class I MHC antigen was presented either as purified membrane-bound molecules incorporated into protein micelles or as a water-soluble preparation containing soluble RT1.A class I molecules. The amount of RT1.A class I contained in each preparation was compared with the amount of class I antigen expressed by whole viable liver cells by quantitative absorption analysis using F16.4.4.11 mAb. The results demonstrated that DA recipients pretreated with a single dose of 1.75 x 10(10) cellular equivalents or multiple doses of 5 x 10(9) cellular equivalents of purified LEW membrane-bound class I molecules, delivered in aggregated micelle form, accepted their LEW renal allografts indefinitely (MST greater than 100 days). In contrast, no prolongation of graft survival was observed using the liver cell cytosol preparation containing soluble RT1.A class I molecules (MST 10 days) at the concentrations tested (10(8) -3 x 10(8) cell equivalents). However, when preoperative treatment with single (greater than or equal to 5 x 10(7) cellular equivalents of soluble class I MHC antigen) or multiple doses (greater than or equal to 10(7) cellular equivalents per dose) of the liver cell cytosol preparation was combined with a subtherapeutic dose of CsA given postoperatively (day +2, 10 mg/kg), suppression of renal allograft rejection was achieved with long-term survival (MST greater than 100 days). The immunologic unresponsiveness observed in both cases was donor specific. PMID- 1604489 TI - The role of leucyl-leucine methyl ester-sensitive cytotoxic cells in skin allograft rejection. AB - Treatment of murine spleen cells (SpC) with L-leucyl-L-leucine methyl ester (Leu Leu-OMe) depletes L3T4(+) and Lyt2(+) cytotoxic T lymphocyte precursors and the capacity to generate lethal graft-versus-host disease in semiallogeneic class I + II MHC and multiple non-MHC-disparate recipient mice, whereas T helper cell function is preserved. In the present studies the role of Leu-Leu-OMe-sensitive CTL in skin graft rejection was examined. C57BL/6J (B6) mice were serially thymectomized, lethally irradiated, reconstituted with T cell-depleted bone marrow, and treated with intraperitoneal injections of anti-L3T4 and anti-Lyt2 monoclonal antibodies. These adult thymectomized, bone marrow-reconstituted, T cell-depleted (ATXBM, TCD) mice were unable to reject B6xDBA/2F1 (B6D2F1) skin grafts. When such ATXBM, TCD mice were reconstituted with 7 x 10(7) control B6 SpC, acute rejection of B6D2F1 skin was observed. When B6 donor SpC were Leu-Leu OMe-treated prior to transfer to ATXBM, TCD mice, uniform rejection of B6D2F1 skin grafts was still observed, although a significant delay in the time to rejection was observed. More rigorous T cell depletion of ATXBM, TCD host mice by infusion of antithymocyte globulin did not prevent delayed rejection of B6D2F1 skin initiated by transfer of Leu-Leu-OMe-treated B6 SpC. Despite the lack of complete prevention of skin allograft rejection, Leu-Leu-OMe treatment of B6 donor cells prevented lethal GVHD even in thymectomized B6D2F1 recipients. Precursors of anti-B6D2F1-specific CTL were greatly reduced or undetectable in unreconstituted ATXBM, TCD mice or in irradiated B6D2F1 recipients of Leu-Leu-OMe treated B6 SpC. By contrast, ATXBM, TCD recipients of Leu-Leu-OMe-treated B6 SpC were found to contain a population of anti-class I MHC-specific CTL precursors of host origin within 28 days of reconstitution. These findings have indicated a number of features of the cells involved in skin graft rejection. First, Leu-Leu OMe-sensitive CTL play a major role in acute rejection of class I + II MHC and multiple non-MHC antigen-disparate skin grafts. Moreover, the thymus-independent expansion of host-derived CTL precursors in ATXBM, TCD mice reconstituted with syngeneic Leu-Leu-OMe-resistant T helper cells also appears to play a role in mediating rejection of allogeneic skin grafts. PMID- 1604490 TI - Reconstitution of (BALB/c x B6)F1 normal mice with stem cells and thymus from nonobese diabetic mice results in autoimmune insulitis of the normal hosts' pancreases. AB - The NOD mouse develops immune-mediated diabetes mellitus characterized by T cell infiltration and destruction of pancreatic islet tissue. We wished to determine whether one contributing factor was an abnormality of the NOD pancreas that caused it to elicit an attack by NOD T cells. Therefore we constructed mice that had an NOD immune system and a non-NOD host pancreas. We found that these animals with only an NOD immune system developed both insulitis and diabetes in their non NOD pancreas. We conclude that the NOD pancreas is not unique in its ability to elicit an autoimmune attack from NOD T cells. PMID- 1604491 TI - Specificity of lymphocytotoxic antibodies formed after cardiac transplantation and correlation with rejection episodes. AB - Eighty-two patients have been studied to determine the class and specificity of lymphocytotoxic antibodies produced during the 6 months following cardiac transplantation. Weekly serum samples were monitored for panel-reactive lymphocytotoxic antibodies (PRA) and donor reactive lymphocytotoxic antibodies using dithiothreitol to determine immunoglobulin class. Sera containing donor reactive antibodies were further analyzed in a cytotoxic inhibition assay to determine whether the antibodies were directed against HLA or non-HLA determinants. A total of 67 (82%) of the patients produced detectable PRA following transplantation, no correlation was found between PRA and the incidence and severity of rejection. In 33 cases where an HLA specificity was defined, the antibody was not directed against the donor HLA phenotype. In contrast, the 32 (53%) recipients who had formed donor-reactive antibodies within 6 months of operation had required significantly more antirejection therapy (methylprednisolone) than the crossmatch-negative recipients (P less than 0.01). This was the case for both IgG and IgM responses. Of 24 positive donor responses, 18 were found to be specific for HLA antigens. These were both IgM (6 cases) and IgG (12 cases) HLA-specific antibodies, and their occurrence was strongly correlated with rejection (P less than 0.001). PMID- 1604492 TI - Prolongation of rat heart allograft survival using cyclosporine and enisoprost, a prostaglandin E1 analog. PMID- 1604493 TI - Prevention of contamination of isolated porcine islets of Langerhans. PMID- 1604494 TI - Aortic valve endocarditis in a liver transplant recipient--successful management by aortic valve replacement. PMID- 1604495 TI - The blood perfusion of transplanted pancreatic islets--evidence of a maturation of the blood-flow response to D-glucose with time after implantation. PMID- 1604496 TI - Colchicine-induced myoneuropathy in a renal transplant patient. PMID- 1604497 TI - Early recurrence of hemolytic uremic syndrome in a renal transplant recipient during prophylactic OKT3 therapy. PMID- 1604498 TI - Backtable angioscopy to evaluate the renal artery. PMID- 1604499 TI - The Chacma baboon as an organ donor for man. PMID- 1604500 TI - The influence of HLA-A2 subtype mismatch on renal allograft survival. PMID- 1604501 TI - Microbial contamination of solid-organ donor transport fluids leading to systemic infection. PMID- 1604502 TI - Successful cryopreservation of porcine pancreatic islets. PMID- 1604504 TI - Experimental models for organ preservation: isologous rat pancreatic islets compared with autologous dog kidneys. PMID- 1604503 TI - In vitro quality control of porcine pancreatic islets correlated with in vivo function following intrasplenic autotransplantation. PMID- 1604506 TI - Reinnervation of transplanted pancreatic islets: a comparison between islets implanted into the kidney, spleen, or liver. PMID- 1604505 TI - Cold storage preservation with University of Wisconsin solution of the pancreatic gland combined with islets in a dog model. PMID- 1604507 TI - Human islet preparations and the expression of MHC antigens. PMID- 1604508 TI - An in vitro assessment of human fetal pancreatic islets of Langerhans in culture. PMID- 1604509 TI - Abrogation of islet immunogenicity using an anti-MHC class I monoclonal antibody. PMID- 1604510 TI - Extended functional survival of murine islet allografts with 15-deoxyspergualin. PMID- 1604511 TI - Detrimental effect of prednisone on canine islet autograft function. PMID- 1604512 TI - Long-term parenteral nutrition in children: liver and gallbladder disease. PMID- 1604513 TI - 263 patient-years of home parenteral nutrition in children. PMID- 1604514 TI - Which patients need small bowel transplantation for neonatal short bowel syndrome? PMID- 1604515 TI - Potential small bowel transplant recipients in the United Kingdom. PMID- 1604516 TI - Progress with small bowel enterocyte culture and transplantation. PMID- 1604517 TI - Surgical technique for combined liver/intestine transplantation in the rat. PMID- 1604518 TI - Graft morphology and serum chemistry profile during chronic rejection of intestinal allografts in the rat. PMID- 1604519 TI - High-frequency ultrasound detects abnormal bowel wall after porcine small bowel transplantation. PMID- 1604520 TI - Long-term survival of portoportal venous drainage in rats with small bowel transplantation. PMID- 1604521 TI - The effect of bowel content on ischemia injury of the small intestine. PMID- 1604523 TI - Colonoscopy to monitor small bowel transplants in the rat. PMID- 1604522 TI - Duodenal gross and microscopic findings after spleno-duodeno-pancreatic allotransplantation in the pig. PMID- 1604524 TI - Short segmental intestinal transplantation in rats--functional comparison of jejunal and ileal grafts. PMID- 1604525 TI - A miniature swine model for intestinal transplantation. PMID- 1604526 TI - Small bowel preservation: evolution of methods and ideas, and current concepts. PMID- 1604527 TI - Viability testing of cold stored small bowel using the "everted sac" technique. PMID- 1604528 TI - Morphologic and histologic alterations after small-bowel transplantation--a comparison of different perfusion solutions. PMID- 1604529 TI - Use of tissue blood flow and high energy phosphate content to predict small bowel graft survival. PMID- 1604530 TI - The protective effect of administered CoQ10 against small intestinal damage caused by ischemia reperfusion. PMID- 1604531 TI - Improved small intestinal preservation with additional use of superoxide dismutase to University of Wisconsin solution. PMID- 1604533 TI - Ischemia and long-term reperfusion injury in a one-stage orthotopic rat small bowel transplantation model: when and where to biopsy? PMID- 1604532 TI - Small intestine energy metabolism during hypothermic storage using different protecting solutions. PMID- 1604534 TI - Intestinal distribution and leakage of hyaluronan in small bowel allografting in the rat. PMID- 1604535 TI - Alterations in intestinal flora following small bowel transplantation. PMID- 1604536 TI - Rapid translocation of bacteria in small bowel transplantation. PMID- 1604537 TI - Glutamine prevents mucosal injury after small bowel transplantation. PMID- 1604538 TI - The long-term function of canine jejunoileal autotransplants--insights into allograft physiology. PMID- 1604539 TI - Endotoxemia after small bowel transplantation. PMID- 1604540 TI - Patterns of enteric nervous distribution after small bowel transplantation. PMID- 1604541 TI - Changes in motility, transit time, and absorption following surgical transection of the jejunum. PMID- 1604542 TI - Successful lymphangiographic investigation of mesenteric lymphatic regeneration after orthotopic intestinal transplantation in rat. PMID- 1604543 TI - Glucagon responses to oral glucose in jejunoileal allotransplanted dogs. PMID- 1604544 TI - Diminished functional capacity and compromised mucosal integrity in acute rejecting DLA-matched and mismatched canine small bowel allografts. PMID- 1604546 TI - Intestinal permeability after small intestinal transplantation and cyclosporine treatment. PMID- 1604545 TI - Studies on bioavailability of vitamin A--uptake in rats with acute graft rejection following small bowel transplantation and in rats with short bowel syndrome. PMID- 1604547 TI - Digestive and absorptive function of orthotopic small intestinal transplantation in the rat. PMID- 1604548 TI - Migrating myoelectric complexes in rat ileal isografts are reduced in the fasted but not the fed state. PMID- 1604549 TI - Changes in intestinal mucosal protective function after small bowel transplantation. PMID- 1604551 TI - An immunosuppressive regimen that reduces graft cell emigration following small bowel transplantation. PMID- 1604550 TI - Host vs graft and graft vs host reactions after allogeneic heterotopic small bowel transplantation in the rat. PMID- 1604552 TI - The role of passenger leukocytes in the immunogenicity of intestinal and cardiac allografts in the rat. PMID- 1604553 TI - Comparison of functional activity in host and graft mesenteric lymphoid tissue of rats receiving syngeneic heterotopic small bowel allografts with portal or systemic drainage. AB - With the accompanying paper these studies provide further evidence that functionally important lymphoid cell trafficking takes place in mesenteric tissue under the apparent control of factor(s) filtered by hepatic tissue. The role that these regulatory mechanisms have to play on survival of vascular allografts with venous drainage into either the portal or systemic circulation remains to be elucidated. PMID- 1604554 TI - Natural killer activity is down-regulated following allogeneic small bowel transplantation. PMID- 1604556 TI - Lethal graft-vs-host disease after cyclosporine therapy in recipients of sensitized small bowel allografts. PMID- 1604555 TI - Immunoreactivity of T lymphocytes propagated from biopsies of human cadaveric small intestine allografts: a serial study of four patients. PMID- 1604557 TI - Priming the recipient abrogates the inhibitory effect of cyclosporine on specific sIgA production against cholera toxin in small bowel transplantation. PMID- 1604558 TI - Successful canine small bowel transplantation using major histocompatibility complex matched segmental ileal allografts. PMID- 1604559 TI - Comparison of the small intestine after multivisceral transplantation with the small intestines transplanted with portal or caval drainage. PMID- 1604560 TI - Emigration of graft cells to the host in small bowel transplantation. PMID- 1604561 TI - Altered cell trafficking in mesenteric lymphoid tissue following syngeneic heterotopic small bowel transplantation in rodents. AB - These data indicate that in rat heterotopic syngeneic SBT, the venous drainage system of the graft has profound effects on cell recovery in the gut-associated lymphoid tissue of both graft and host. Depending on the functional status of the same lymphoid tissue (Gorezynski, personal communication, 1992) one could thus anticipate significant perturbation of host-antigraft (and GVH) reactivity in allogeneic situations according to the venous drainage used. The mechanism(s) responsible for these effects have not been investigated. However, one testable hypothesis is that (a) factor(s) from the gut can control lymphoid recirculation within the mesenteric lymphoid tissue, and that this (these) factor(s) are absorbed under normal circumstances by hepatic tissue. PMID- 1604562 TI - Serum NO2-/NO3- from oxidative L-arginine metabolism: a possible marker for small bowel allograft rejection. PMID- 1604563 TI - Rat intestinal epithelial cells as accessory cells in alloimmune responses. PMID- 1604564 TI - Genetic aspects of graft-vs-host reaction after small bowel transplantation with and without mesenteric lymphadenectomy. PMID- 1604565 TI - Serum levels of interleukin-6, tumor necrosis factor-alpha, and interleukin-2 in rejecting human small bowel allografts. PMID- 1604566 TI - Cyclosporine inhibits specific sIgA production against cholera toxin but not trinitrophenyl-lipopolysaccharide in small bowel transplantation. PMID- 1604567 TI - The effect of rapamycin on orthotopic small bowel transplantation in the rat. PMID- 1604568 TI - Small bowel transplantation in rats using RS-61443: effect on GVHD and rejection. PMID- 1604569 TI - Mechanism of graft-versus-host disease and inhibition with deoxyspergualin on small bowel transplantation in rats. PMID- 1604571 TI - Small bowel transplantation in the rat: the effect of donor-specific transfusion 24 hours pretransplant and cyclosporine. PMID- 1604570 TI - The effects of 16,16-dimethyl prostaglandin E2 therapy alone and in combination with low-dose cyclosporine on rat small intestinal transplantation. PMID- 1604572 TI - The effect of ultraviolet B-irradiated leukocyte transfusions in intestinal transplantation. PMID- 1604573 TI - Orthotopic porcine small bowel transplantation using low-dose cyclosporine in triple immunosuppressive therapy. PMID- 1604574 TI - Total orthotopic small bowel transplantation with cyclosporine: morphology and function in a swine model. PMID- 1604575 TI - Rapamycin suppression of host-versus-graft and graft-versus-host disease in MHC mismatched rats. PMID- 1604576 TI - The interaction of gamma irradiation of the allograft and recipient administration of cyclosporine in rat small bowel transplantation. PMID- 1604577 TI - Donor pretreatment with rapamycin delays rejection following intestinal allotransplantation. PMID- 1604578 TI - Effect of polyethylene glycol on rat small bowel rejection. PMID- 1604579 TI - Failure of donor irradiation to prolong allograft survival in small bowel transplantation in rats. PMID- 1604580 TI - The effect of blood transfusions on graft-versus-host disease in small intestine transplantation in rats. PMID- 1604581 TI - RS-61443 prevents graft-versus-host disease but not rejection in allogeneic rat small bowel transplants. PMID- 1604582 TI - Amelioration of graft-versus-host disease following bowel transplantation with recipient specific leukocyte transfusion. PMID- 1604583 TI - Changes in small intestinal microflora following small bowel transplantation in the rat and bacterial translocation in rejection and graft-versus-host disease. PMID- 1604584 TI - Immunohistochemical assessment of mucosal biopsies following human intestinal transplantation. PMID- 1604585 TI - Lymphocyte trafficking using in situ hybridization and physioanatomy of the intestinal immune system after human small bowel transplantation. PMID- 1604586 TI - Histologic monitoring of human small bowel allografts with clinical correlation. PMID- 1604587 TI - Grading system for histologic changes in rat small bowel transplants. PMID- 1604588 TI - Liver transplantation regulates a graft-versus-host reaction in the rat. PMID- 1604589 TI - The effect of donor-recipient strain combinations in combined liver/intestine transplantation in the rat. PMID- 1604590 TI - Long-term small bowel graft survival induced by spontaneously tolerated liver allografts in inbred rat strains. PMID- 1604591 TI - Multivisceral upper-abdominal allotransplantation in the pig. PMID- 1604592 TI - Multivisceral abdominal allotransplantation in pigs: small bowel aspects. PMID- 1604594 TI - Multivisceral and intestinal transplantation. PMID- 1604593 TI - Pattern of rejection after multivisceral transplantation in stomach, small bowel, and pancreas. PMID- 1604595 TI - Two and one-half-year follow-up after isolated cadaveric small bowel transplantation in an infant. PMID- 1604596 TI - Successful multivisceral transplantation. PMID- 1604597 TI - Liver-intestinal transplantation: report of a case. PMID- 1604598 TI - Extreme short bowel syndrome in neonates: an indication for small bowel transplantation? PMID- 1604599 TI - Successful small intestine transplantation. PMID- 1604600 TI - Clinical intestinal transplantation: focus on complications. PMID- 1604601 TI - The coming of age of small bowel transplantation: a historical perspective. PMID- 1604602 TI - Developmental issues in childhood small bowel transplantation: eating and elimination. PMID- 1604603 TI - Role of duodenal biopsy in bladder-drained pancreas transplants. PMID- 1604604 TI - Infectious complications after human small bowel transplantation. PMID- 1604605 TI - Psychiatric psychosocial and ethical aspects of small bowel transplantation. PMID- 1604606 TI - Pancreatic transplantation: state of the art. PMID- 1604607 TI - Hyperinsulinemia and macroangiopathy: the epidemiological perspective. PMID- 1604608 TI - Pancreas transplantation: the choice of the best technique. PMID- 1604609 TI - Pancreatic transplantation with enteric exocrine diversion: experience with 120 cases. PMID- 1604610 TI - Metabolic complications in combined kidney/pancreas transplantation. PMID- 1604611 TI - Pancreas transplantation with portal venous drainage and enteric exocrine diversion: a new technique. PMID- 1604612 TI - How large is the demand for simultaneous pancreas and kidney transplantation? PMID- 1604613 TI - Pancreas transplants in nonuremic and posturemic diabetic patients. PMID- 1604614 TI - Segmental versus total duodenopancreatic grafts: a 2-year randomized study. PMID- 1604615 TI - Low incidence of urinary tract infection after combined kidney and segmental pancreas transplantation with bladder drainage. PMID- 1604616 TI - Prevention and management of hematuria in combined pancreas-kidney transplant recipients with pancreaticoduodenocystostomy. PMID- 1604617 TI - A novel approach to pancreas preservation: does the gaseous milieu matter? PMID- 1604618 TI - Role of oxygen radicals and synergistic effect of superoxide dismutase and catalase on ischemia-reperfusion injury of the rat pancreas. PMID- 1604619 TI - Pancreas endocrine function in pigs after segmental pancreas autotransplantation with either systemic or portal venous drainage. PMID- 1604620 TI - Morphological changes of B cells in canine autotransplanted pancreas. PMID- 1604621 TI - Surgical experience with 50 consecutive extraperitoneal duct-occluded segmental pancreatic allografts: critical review of the procedure and postoperative complications. PMID- 1604622 TI - Reconstruction of the vascular pedicle of the pancreatic graft after combined harvesting with liver: comparison among different surgical options. PMID- 1604623 TI - Converting exocrine drainage from bladder to bowel in recipients of whole pancreaticoduodenal transplants. PMID- 1604625 TI - Duct-enterostomy as a treatment of pancreatic fistula in a bladder-drained pancreas transplant. AB - A case of combined pancreaticoduodeno-renal transplant with good graft function was complicated by recurrent episodes of graft pancreatitis treated by vesical catheter drainage. Four months after transplantation, a fistula from the pancreatic body associated with ascitis was identified. Anastomosis between pancreatic fistula and an individualized jejunal loop was performed. The duodenocystostomy was not disconnected. A splint placed inside the wirsung was exteriorized percutaneously through the jejunal loop and removed 30 days after the operation. Both kidney and pancreas grafts are functioning normally 2 years after transplantation. PMID- 1604624 TI - Urologic complications in diabetic recipients of combined kidney/pancreas grafts versus kidney grafts alone. PMID- 1604626 TI - Early postoperative surgical complications: comparison of segmental duct-injected versus whole bladder-drained pancreas transplantation. PMID- 1604627 TI - Pancreatic graft outcome after combined whole pancreas and liver retrieval. PMID- 1604628 TI - Morphological and functional comparisons of autotransplanted pancreas after 72- and 96-hour cold storage preservation in the canine. PMID- 1604629 TI - Insulin insensitivity and glucose effectiveness in type I diabetic allograft pancreas recipients. PMID- 1604630 TI - Systemic (nonurinary tract) sepsis in 102 consecutive whole-organ pancreas transplants. PMID- 1604631 TI - Quality of metabolic control at 2 to 12 years after a pancreas transplant. PMID- 1604632 TI - Metabolic results at 6 and 12 months after pancreas transplantation. PMID- 1604633 TI - Lipoprotein level improvements with pancreas-kidney transplantation. PMID- 1604634 TI - Lipid metabolism following heterotopic pancreas transplantation with special reference to steroid therapy. PMID- 1604635 TI - Long-term lipid metabolism in recipients of whole-organ pancreas transplants with normal glucose tolerance. PMID- 1604636 TI - Serum lipids after pancreas and kidney transplantation. PMID- 1604637 TI - Dietary advice and lipid metabolism in insulin-dependent diabetes mellitus kidney and pancreas-transplanted patients. PMID- 1604638 TI - Life quality of pancreatic transplant recipients: a comparison. PMID- 1604639 TI - Experience with single pancreatic transplantation in preuremic diabetic recipients in Stockholm. PMID- 1604640 TI - The influence of combined kidney-pancreas transplantation on advanced diabetic retinopathy. PMID- 1604641 TI - Gastric emptying improvement after simultaneous segmental pancreas and kidney transplantation. PMID- 1604642 TI - Diabetic neuropathy four years after pancreas transplantation. PMID- 1604643 TI - The point of no return in rat diabetic nephropathy: effects of pancreatic transplantation. PMID- 1604644 TI - Effect of pancreas transplants on secondary complications of diabetes: review of observations at a single institution. PMID- 1604645 TI - Role of heterotopically transplanted segmental pancreas in physical performance in humans. PMID- 1604646 TI - Mortality risk for technically successful vs technically failed bladder drained pancreas transplants and causes of death. PMID- 1604648 TI - Electrophysiologic evolution of diabetic polyneuropathy after combined pancreas and renal transplantation. PMID- 1604647 TI - Morbidity following simultaneous pancreas-kidney transplants vs kidney transplants alone in diabetic patients. PMID- 1604649 TI - Quality of life in diabetic patients prior to or after pancreas transplantation in relation to organ function. PMID- 1604650 TI - Ophthalmologic follow-up of type I diabetic patients after kidney and pancreas transplantation. PMID- 1604651 TI - Evolution of diabetic neuropathy after kidney-pancreas transplantation. PMID- 1604652 TI - Whole pancreatic and islet blood flow after syngeneic pancreaticoduodenal transplantation in the rat. PMID- 1604653 TI - Impaired B-cell function after lobe-specific hemipancreatectomy. PMID- 1604654 TI - Long-term glucose homeostasis and insulin secretion following segmental heterotopic pancreas transplantation. PMID- 1604655 TI - Long-term pancreatic and pancreaticoduodenal isografts maintain normal insulin secretory function in Lewis rats. PMID- 1604656 TI - Long-term glucose control after pancreatic transplantation with enteric exocrine diversion. PMID- 1604657 TI - Importance of cyclosporine dosage and blood levels in simultaneous pancreas and kidney transplant success. PMID- 1604658 TI - Synergistic effect of rapamycin and cyclosporine in pancreaticoduodenal transplantation in the rat. PMID- 1604659 TI - Effect of triple drug immunosuppressive therapy in pigs grafted with highly purified islets. PMID- 1604660 TI - Cyclosporine therapy concomitant with renal allotransplantation induces tolerance to subsequent donor MHC-identical islet grafts. PMID- 1604661 TI - Exocrine dysfunction evaluation of bladder-drained pancreaticoduodenal transplants using a transcystoscopic biopsy technique. PMID- 1604662 TI - Urine cytologic monitoring for rejection after vascularized pancreas transplantation. PMID- 1604663 TI - Pancreatic juice neopterin excretion--a reliable marker of pancreas allograft rejection. PMID- 1604664 TI - Is HLA matching worthwhile in pancreatic transplantation? PMID- 1604665 TI - Randomized trial of induction immunosuppression with anti-IL2-R monoclonal antibody 33B3.1 and rabbit antithymocyte globulin following simultaneous pancreas and kidney transplantation. PMID- 1604666 TI - Pancreas induces graft-vs-host disease when transplanted en bloc with liver and small bowel. PMID- 1604667 TI - Immunologic aspects of pancreas grafting in multivisceral transplantation. PMID- 1604668 TI - Pancreatic juice cytology can diagnose both rejection and pancreatitis. PMID- 1604669 TI - Infections in simultaneous pancreas transplantation duct: occlusion vs bladder drainage. PMID- 1604670 TI - Histologic classification of pancreatic allograft rejection in the rat. PMID- 1604671 TI - Allograft of microencapsulated islets in agarose gel in streptozotocin-induced and nonobese diabetic mice. PMID- 1604672 TI - Intravascular transplantation of microencapsulated islets in diabetic dogs. PMID- 1604673 TI - Barium-alginate beads for immunoisolated transplantation of islets of Langerhans. PMID- 1604674 TI - Long-term treatment of type I diabetes in 28 patients using two different implantable programmable pumps. PMID- 1604675 TI - Implantation of a hybrid artificial pancreas in diabetic dogs. PMID- 1604676 TI - Influence of abdominal location of the catheter on the efficacy of intraperitoneal insulin infusion using implantable and programmable pumps in type I diabetes. PMID- 1604677 TI - Short-term treatment by implantable pump does not impair lipoprotein pattern in IDDM patients. PMID- 1604678 TI - Comparison of intraperitoneal insulin infusion (using implantable pump) and subcutaneous insulin administration: preliminary results of a crossover study. PMID- 1604680 TI - Agarose microcapsule applied in islet xenografts (hamster to mouse). PMID- 1604679 TI - In vitro testing of rat and porcine islets microencapsulated in barium alginate beads. PMID- 1604681 TI - Diffusion properties of an artificial membrane used for Langerhans islets encapsulation: interest of an in vitro test. PMID- 1604682 TI - Toward a new device for islet cell immunoisolation in pancreatic transplantation. PMID- 1604683 TI - The effect of capsule composition on the viability and biocompatibility of sodium alginate/poly-L-lysine encapsulated islets. PMID- 1604684 TI - Bovine pancreas as a source of islets for xenotransplantation. PMID- 1604685 TI - Intraportal islet allografts in type I diabetes mellitus. PMID- 1604686 TI - Human islet allotransplantation in 18 diabetic patients. PMID- 1604687 TI - Regional cytokine changes following OKT3 induction for islet cell transplantation in humans: early increase in portal and systemic levels of interleukin-6 and tumor necrosis factors. PMID- 1604688 TI - Allotransplantation of fresh islets in four type I diabetic patients. PMID- 1604690 TI - Long-term function of islet autotransplants. PMID- 1604689 TI - Human islet cotransplantation with liver or kidney. PMID- 1604691 TI - Evidence of xenograft function in a diabetic patient grafted with porcine fetal pancreas. PMID- 1604692 TI - The bioburden of 590 consecutive human pancreata for islet transplant research. PMID- 1604693 TI - Histologic finding of pancreatic islet tissue following intraportal human islet allotransplantation. PMID- 1604694 TI - Xenografts of human fetal pancreas regulate blood glucose to human levels. PMID- 1604695 TI - Cellular composition of islet cell suspensions for transplantation. PMID- 1604696 TI - Porcine islet function: effects of arginine, leucine, and butyrate. PMID- 1604697 TI - Engraftment of isolated islets after syngeneic transplantation into normal and diabetic mice. PMID- 1604698 TI - Long-term survival of donor-specific pancreatic islet xenografts in fully xenogeneic chimeras. PMID- 1604699 TI - Survival of human hepatocellular aggregates in athymic mice. PMID- 1604700 TI - Comparison of the potency of fetal pig pancreatic proislets and fragments to reverse diabetes. PMID- 1604701 TI - The impact of T cells in nonspecific destruction of beta cells in mice. PMID- 1604702 TI - Endocrine function of long-term surviving dogs with nonisolated pancreatic islet fragment autotransplantation. PMID- 1604703 TI - Longitudinal metabolic effects of islet isografts. PMID- 1604704 TI - Islet rest protects against exhaustion of insulin production in transplanted islets. PMID- 1604705 TI - Allograft of microencapsulated islets in agarose gel in streptozotocin-induced and nonobese diabetic mice. PMID- 1604706 TI - Abdominal testis transplantation prevents rejection of islet isografts in low dose streptozocin-induced diabetes. PMID- 1604707 TI - Recurrence of diabetes after islet transplantation in the BB rat. PMID- 1604708 TI - Neurobiological perspectives on drugs of abuse. PMID- 1604709 TI - Drugs of abuse: behavioural principles, methods and terms. AB - Current understanding of drug abuse has been greatly influenced by the emphasis on drug-seeking behaviour as the common element. The three main attributes of drugs that maintain, direct and regulate drug-seeking behaviour are their positively reinforcing and discriminative and aversive stimulus properties. Each process may be analysed in terms of underlying behavioural and neural mechanisms that are mutually complementary and interactive. Environmental stimuli conditioned to the effects of the drugs also play a key role in eliciting and maintaining drug-seeking behaviour. Both the behavioural and the neural mechanisms are subject to modulating variables such as social, environmental and genetic factors, including the previous behavioural and pharmacological history of the individual. Thus, the behavioural approach to addiction does not preclude important roles for other factors, but rather seeks to integrate them into a comprehensive theoretical framework strongly linked to empirical data. PMID- 1604710 TI - Drugs of abuse: anatomy, pharmacology and function of reward pathways. AB - Drugs of abuse are very powerful reinforcers, and even in conditions of limited access (where the organism is not dependent) these drugs will motivate high rates of operant responding. This presumed hedonic property and the drugs' neuropharmacological specificity provide a means of studying the neuropharmacology and neuroanatomy of brain reward. Three major brain systems appear to be involved in drug reward--dopamine, opioid and GABA. Evidence suggests a midbrain-forebrain-extrapyramidal circuit with its focus in the nucleus accumbens. Data implicating dopamine and opioid systems in indirect sympathomimetic and opiate reward include critical elements in both the nucleus accumbens and ventral tegmental areas. Ethanol reward appears to depend on an interaction with the GABAA receptor complex but may also involve common elements such as dopamine and opioid peptides in this midbrain-forebrain-extrapyramidal circuit. These results suggest that brain reward systems have a multidetermined neuropharmacological basis that may involve some common neuroanatomical elements. PMID- 1604711 TI - Neurobiology of opiate abuse. AB - Opiates interact with cell surface receptors on neurons involved in the transmission of information along neural pathways that are related to behaviours essential for the life of the self and of the species. Opiates are provided with powerful and multifaceted rewarding properties that are fundamental for the acquisition, maintenance and relapse of opiate addiction. Gaetano Di Chiara and Alan North argue that both dopaminergic and non-dopaminergic systems are involved in opiate reward, and that opiate addiction results from adaptive and learning processes involving both positive reinforcing mechanisms related to the rewarding properties of opiates and negative reinforcing mechanisms related to the aversive properties of withdrawal in dependent subjects. PMID- 1604712 TI - Neurobiology of cocaine abuse. AB - The recent escalation of cocaine abuse has increased awareness of the need to understand the behavioral effects of cocaine and the determinants of those effects. Cocaine alters both conditioned and unconditioned behavior, and has prominent reinforcing and subjective effects that are particularly relevant to its abuse. An increase in CNS dopamine neurotransmission, resulting from a competitive blockade of high-affinity dopamine uptake mediated by both D1 and D2 dopamine receptors, is a primary determinant of the behavioral effects of cocaine. Either tolerance or sensitization may develop with repeated administration of cocaine. Dependence also develops, although the behavioral changes associated with cocaine withdrawal are subtle. Although numerous CNS changes have been associated with repeated administration of cocaine, the neuropharmacological mechanisms that underlie the behavioral changes that occur with repeated administration remain to be firmly established. Bill Woolverton and Ken Johnson stress that continued collaboration between behavioral pharmacologists and neuroscientists is critical for a complete understanding of the effects of cocaine. PMID- 1604713 TI - Neurobiology of marijuana abuse. AB - Marijuana has a long history of abuse yet, as described here by Mary Abood and Billy Martin, there is little evidence that animals will self-administer the primary psychoactive constituent, tetrahydrocannabinol, or that marijuana stimulates brain reward pathways. While marked tolerance develops to marijuana, it has been difficult to demonstrate physical dependence, and until recently the mechanisms by which cannabinoids produced their behavioral effects were poorly defined. The development of new synthetic analogs played a critical role in the characterization and cloning of the cannabinoid receptor. Insight into cannabinoid receptors may lead to a better understanding of marijuana abuse in humans and provide new therapeutic strategies for several disorders. PMID- 1604714 TI - Genetic approaches to drug dependence. AB - Pharmacogenetic studies with drugs of abuse are proliferating. Many genetic animal models are now available for studies of the mechanisms of action of a variety of drugs. These models provide unique, genetically defined populations of extremely sensitive and insensitive animals for neuropharmacological analyses. John Crabbe and John Belknap describe how molecular biological methods are being applied to these models in combination with more traditional genetic mapping strategies to identify single genes of importance to drug effects. Pharmacogenetic approaches offer the hope of establishing commonalities of mechanisms among abused drugs. PMID- 1604715 TI - Reducing the perinatal mortality rate in developing countries. PMID- 1604716 TI - Oxygen concentrators for the smaller hospital--a review. PMID- 1604717 TI - Herpes zoster as an indicator of HIV infection in Africa. AB - In areas where resources for health information are limited, the incidence of herpes zoster can usefully be monitored as an indicator of HIV infection. A sudden parallel rise of the number of symptomatic HIV cases and herpes zoster cases was observed in a northern district of Zimbabwe. Herpes zoster was made locally reportable. Three years later the incidence of herpes zoster and HIV in the hospital and of herpes zoster in the surrounding rural health centres was analysed. The herpes zoster attack rate and the HIV seropositivity rate of herpes zoster patients resembled those elsewhere in Africa. The distribution of cases of zoster was comparable with that of HIV infection. PMID- 1604718 TI - Emergency symphysiotomy for the trapped head in breech delivery: indications, limitations and method. AB - Careful case selection can avoid most obstetrical emergencies. However, even with optimum management of breech labour, the fetal head may become trapped. Since doctors in developing nations must be prepared for this dire situation, this article reviews breech case selection and outlines the steps in breech delivery, illustrating symphysiotomy for the entrapped head. The limitations and precautions associated with symphysiotomy are stressed. PMID- 1604719 TI - Illegal induced abortion: a study of 74 cases in Ile-Ife, Nigeria. AB - Seventy-four women with complications of induced abortion were studied prospectively at the Obafemi Awolowo University, Nigeria. Twenty of the women were interviewed privately to elicit confidential information and also to determine their attitudes to contraception and to the Nigerian national abortion law. The results showed that abortion is prevalent in all classes of women and in married as well as unmarried women. There were 13 maternal deaths, accounting for 35% of the maternal mortality in the hospital during the period. Sepsis was the most common cause of death, and most of the abortions complicated by sepsis had been performed by medical practitioners. Interviews with the women revealed that most of them had knowledge of contraception but were unwilling to use it because of wrong information. Most women did not know that abortion is illegal in Nigeria, but felt that it should be. Measures that could be of value in reducing abortion-associated maternal mortality in Nigeria include training and retraining of physicians in the management of abortion and of abortion complications, family planning education of all fertile women, provision of confidential family planning services and liberalization of the abortion law. PMID- 1604720 TI - Autologous transfusion for elective surgery and caesarean section in Uganda. PMID- 1604721 TI - Improving drug utilization at local level--an opinion. PMID- 1604722 TI - Perinatal mortality in a district general hospital, upper east region, Ghana. PMID- 1604723 TI - Rats, fever and sudden deafness in Sierra Leone. PMID- 1604724 TI - Atrophic rhinitis: a familial disease? PMID- 1604725 TI - Control of plague. PMID- 1604726 TI - A new look at typhoid. PMID- 1604727 TI - Helicobacter pylori and non-ulcer dyspepsia in Zambia. PMID- 1604728 TI - Rheumatology and Africa. PMID- 1604729 TI - Heterotopic triplets. PMID- 1604730 TI - Diagnosing tuberculosis in malnourished children. PMID- 1604731 TI - Tuberculosis and malnourished children. PMID- 1604732 TI - Intravenous drips. PMID- 1604733 TI - Tuberculosis and malnourished children. PMID- 1604734 TI - Empyema thoracis--open or closed drainage? PMID- 1604735 TI - Handwashing on the wards. PMID- 1604736 TI - Neuroleptic malignant syndrome complicating tetanus treated with chlorpromazine. PMID- 1604737 TI - Chronic scarring dermatoses: remember porphyria cutanea tarda. PMID- 1604738 TI - Subacute sclerosing panencephalitis presenting as cortical blindness. PMID- 1604739 TI - [Atopic dermatitis--many causes and therapeutic possibilities]. PMID- 1604740 TI - [Quality assessment, quality assurance and quality improvement in health care. Concepts and terminology]. AB - At present the topic "quality of health care" takes up a central position in the Danish debate, both among health professionals and politicians. In the present review the terms quality, quality assessment, and quality assurance are attempted defined and described. To assess the quality of health care deliveries it is necessary to establish indicators, criteria and standards. Indicators are defined variables which reflect deviations in quality. Criteria are established determinants of the optimal level of care while standards represent the degree of fulfillment of these. The relationship between indicators, criteria, and standards are illustrated. Quality assurance is a continuous process based on identifying quality problems for a given health delivery, and determining criteria and standards in relation to this. Quality assessment is the data collection and analysis through which the degree of conformity to predetermined standards and criteria are exemplified. If the quality, through this process is found to be unsatisfactory, attempts are made to discover the reason for this. On the basis of this, remedial actions are instituted and the quality reevaluated after a suitable time period. This stepwise process makes quality assurance a dynamic activity where criteria and standards are revised continuously with the overall purpose of improving the quality of health care services. Quality assessment and assurance should be incorporated as routine activities for health professionals. However, development, testing, and validation of the tools and methodologies for this new discipline are research activities. PMID- 1604741 TI - [Capnometry]. AB - Technological advances during recent years and developments in anaesthesiology and intensive care have increased the interest in capnometry (measuring the CO2 content in the respiratory air). The physiological background and the principles of the method are presented. The applicability in clinical work and the limits of the method are presented and discussed. PMID- 1604742 TI - [Complications in patients who underwent appendectomy for mistakenly diagnosed acute appendicitis]. AB - A retrospective investigation was undertaken concerning 552 patients who were submitted to appendectomy on account of suspected acute appendicitis during the period January 1 1983-December 31 1987. The diagnostic certainty was found to be 69%. A total of 14.3% (79/552) developed postoperative complications, including 20 patients in whom normal appendices were removed. Some of the complications were possibly attributable to the cause of the symptoms of acute appendicitis but this was not possible to determine by review of the case records. No differences were found in the frequencies of complications in whom normal appendices were removed as compared with those in whom inflamed appendices were removed. The frequency of perforation was 17.2% (95/552) which is in agreement with the findings in previous investigations. It may thus be concluded that the incidence of complications associated with removal of a normal appendix is no greater than after removal of an inflamed appendix. Removal of a normal appendix is, however, not a harmless procedure. The incidence of "negative appendectomy" must be reduced by meticulous observation and repeated reassessment of the patient and employment of other diagnostic aids e.g. ultrasonic scanning or laparoscopy in order to confirm or refute the diagnosis prior to possible operation. PMID- 1604743 TI - [Endoluminal ultrasonography of the anal canal]. PMID- 1604744 TI - [Anesthesiologic aspects of multiorgan donation]. AB - As of July 1990 brain death was legally recognized in Denmark thereby rendering transplantation of heart, liver and lung possible. Brain death donors are usually treated in neurosurgical or anaesthetic intensive care units. The staff of these units influence the number of donors and also the quality of organs donated. Physiological factors pertinent to brain death donors and pre- and peroperative donor therapy in relation to multiorgan procurement are discussed from the viewpoint of the anaesthetist. Symptomatic therapy aimed at optimizing and maintaining organ function is employed; thus continuing intensive care. Sympathetic and somatic reflex responses to surgical stimulation are to be anticipated, often necessitating analgesics to blunt haemodynamic responses and neuromuscular blocking agents to inhibit movements and/or rigidity. PMID- 1604745 TI - [Incapacitating angina pectoris treated with electric stimulation of the spinal cord]. AB - Thirty patients who had severe incapacitating angina pectoris which had not reacted to the conventional therapeutic measures and which required massive daily opioid consumption were treated with electrical spinal cord stimulation (SCS) by means of a completely implantable stimulation system. The therapeutic effect was good in 87% of the patients who experienced considerably reduced frequency of attacks and markedly reduced opioid consumption (p less than 0.00005). Nine of the patients could reduce opioid consumption and 14 out of 27 could cease their otherwise daily opioid consumption. In four patients, the therapeutic effect was unsatisfactory. In the first 22 patients in whom a unipolar electrode was introduced, displacement of the electrode and subsequent reoperation was a frequent problem. This problem disappeared after change to multipolar electrodes as slight changes in placing of the electrode could easily be compensated for via the external programming equipment. This investigation reveals that SCS is a good therapeutic alternative for this selected patient category. PMID- 1604746 TI - [Cost-benefit analysis of electric stimulation of the spinal cord in the treatment of angina pectoris]. AB - Since August 1988, in Odense Hospital, electric spinal cord stimulation (SCS) has been employed for the treatment of pain in patients with confirmed ischaemic heart disease who suffer from incapacitating angina pectoris despite maximal medical/surgical treatment. The object of the present investigation was to assess not only the social economic consequences of SCS treatment (cost-utility analysis) but also altered quality of life in SCS patients (perception of pain, mobility, function in daily life and physical activity). Sixteen consecutive SCS patients all of whom were resident in the County of Funen and who were submitted to implantation of an SCS system during the period August 1988 to December 1989, participated in this investigation. The results are based on data from the year prior to SCS implantation compared with the subsequent time with SCS treatment. Saving was found at hospital level (reduction in number of admissions) og 40,200 Danish crowns/annum/patient (approximately IJ 3,000) (1989 prices), and for non hospital related expenses a corresponding saving of 16,289 Danish crowns/annum/patient (approximately IJ 1,600) was found mainly on account of reduction in the amount of home nursing required. The total saving was found to constitute 56,489 Danish crowns/annum/patient (approximately IJ 5,600). In addition, improvements were registered in all respects which constituted assessment of the quality of life of the patients. PMID- 1604747 TI - [The roles of primary and secondary health services in the production and utilization of clinical chemical blood analyses. A 5-year survey in the county of Frederiksborg]. AB - The number of clinical chemical analyses performed on blood in the County of Frederiksborg in 1990 was 3.7 per inhabitant. The number of analyses requested increased by only 2.5% since 1986. Approximately 1/3 of the analyses were requested from primary care and about 1/5 of these analyses were performed in the doctors' offices. Approximately 100 different kinds of analyses were requested, but the 10 (20) most frequent analyses requested in 1990 account for 62 (80%) of the analyses requested from the hospitals and 73 (89%) of the analyses requested from primary care. Approximately 50% of the analyses requested for B-hemoglobin and B-sedimentation rate and about 70% of the analyses requested for B-glucose was performed in the doctors' office in 1990. Only the number of analyses requested for B-glucose has increased (50%) since 1986. The three analyses account for more than 90% of the clinical chemical analyses performed on blood in the doctors' offices. The pattern of analyses for the ten most frequent analyses requested from primary care differs from the pattern of analyses requested from the hospitals. As compared with the number of analyses requested for P creatinine, the analyses P-aspartate aminotransferase, P-alkaline phosphatase, B sedimentation rate and B-differential counts were requested more than twice as frequently from primary care as from the hospitals. The pattern of analyses requested for a number of the 20 most frequently requested analyses shows considerably variation from hospital to hospital. This is especially pronounced for B-sedimentation rate and B-leucocyte counts. PMID- 1604748 TI - [Epiphyseal dysplasia of the femoral head in monozygotic twins]. AB - We present monozygotic twin girls with bilateral epiphyseal dysplasia of the femoral head (DECF). DECF is a rare condition reported mainly in boys before the age of five years. It consists of a state of non-ossification characterized by flattening and fragmentation of the femoral head. It is invariably followed by 100% healing. The differential diagnosis is primarily from Legg-Calve-Perthes' disease (LCPD), which, however, occurs mainly after the fifth year followed by aggravation of the symptoms during the following 18 months. This condition leads to secondary degenerative changes in several hips. Although DECF and LCPD may be two entities of the same disease it is necessary to distinguish clinically between them, as the prognosis and the treatment are different. PMID- 1604749 TI - [Inguinal hernias with bladder herniation]. AB - Two cases of inguinal scrotal bladder herniation are reported. Both patients were operated upon with repositioning of the bladder and fascial repair. Herniation of the urinary bladder should be suspected in men aged over 50 years with scrotal herniation and symptoms of bladder outlet obstruction. PMID- 1604750 TI - [How is the medical librarianship functioning?]. PMID- 1604751 TI - [Deliveries in Ireland--travel report about a visit to the National Maternity Hospital in Dublin]. PMID- 1604752 TI - [Nevus and nicotinic acid]. PMID- 1604753 TI - Phase aberration correction using echo signals from moving targets. II: Experimental system and results. AB - A method for correcting errors due to near-field tissue inhomogeneities in phased array ultrasound images is evaluated experimentally. The method uses the brightness of a moving speckle-generating target, such as blood, as a quality factor to correct for unknown phase aberrations. A real time experimental system utilizing the technique has been constructed and is described. Initial results from in vitro studies using a flow phantom are compared to theoretical predictions. The results indicate that the technique can provide significant improvements in image quality when imaging through aberrating media, and may find application in clinical imaging through skull and fatty layers. PMID- 1604754 TI - Microscopic mechanism of attenuation of compressional ultrasonic waves in tissue mimicking phantom materials. AB - An investigation was performed to determine whether the sound-attenuation insuspensions theory of Allegra and Hawley can be used to explain the compressional (longitudinal wave) attenuation of ultrasonically tissue-mimicking materials commonly used in phantoms for testing the performance of medical ultrasound systems. These materials are composed of microscopic graphite particles suspended in a gel. The theory was first tested using materials containing spherical glass beads instead of graphite particles because these materials more closely fit the geometric conditions assumed in the theory. For the glass bead type materials as well as the graphite particle type materials, the attenuation coefficients predicted using the Allegra and Hawley model agreed rather well with experimental measurements over the diagnostic frequency range. PMID- 1604755 TI - Simulated capillary blood flow measurement using a nonlinear ultrasonic contrast agent. AB - This paper proposes a system for measuring slow, small volume blood flow, such as that found in the capillary beds. The method relies on the injection of a strongly nonlinear echocardiographic contrast agent, whose echoes are then analyzed by a modified Doppler process. The contrast agent is necessary to increase the signal-to-clutter ratio from the small blood volume, and to distinguish the blood movement from other moving structures, such as vessel walls or surrounding tissue. The nonlinear properties of this saccharide-based contrast agent are described, as evidenced by experimental evaluation. The contrast agent and signal processing modality are then tested in a blood flow simulator, at velocities as low as 1.5 mm/s, with good results. In addition, an analysis for applying this technique in vivo is presented, accounting for the dynamic and acoustic parameters of the physiological environment. Finally, some specific applications for this method are discussed, including its limitations. PMID- 1604756 TI - Segmenting ultrasound images of the prostate using neural networks. AB - This paper describes a method for segmenting transrectal ultrasound images of the prostate using feedforward neural networks. Segmenting two-dimensional images of the prostate into prostate and nonprostate regions is required when forming a three-dimensional image of the prostate from a set of parallel two-dimensional images. Three neural network architectures are presented as examples and discussed. Each of these networks was trained using a small portion of a training image segmented by an expert sonographer. The results of applying the trained networks to the entire training image and to adjacent images in the two dimensional image set are presented and discussed. The final network architecture was also trained with additional data from two other images in the set. The results of applying this retrained network to each of the images in the set are presented and discussed. PMID- 1604757 TI - Phase aberration correction using echo signals from moving targets. I: Description and theory. AB - Inhomogeneous acoustic velocity in human tissue introduces phase aberration in ultrasonic imaging systems and degrades image quality. A novel technique that employs echo signals from moving diffuse targets, such as flowing blood, as an image quality factor to compensate for phase aberration is described. Such signals can be obtained by subtracting the images of two consecutive target interrogations. The fundamental statistics of the quality factor and other related parameters are developed to provide a theoretical basis for the technique. PMID- 1604758 TI - [Do we need--once again--a new health definition?]. PMID- 1604759 TI - [Do we need an autopsy law?]. AB - The clinical autopsy serves the purpose of identifying the underlying disease as well as the immediate cause of death. It is the major instrument of quality control in the field of medical diagnosis and treatment. In addition, autopsies are of great importance with regard to the epidemiology of diseases, to the identification of hitherto unknown disease entities and to modified clinical courses of well-known disorders. Moreover, clinical autopsies have a significant impact on the medical education of students as well as of physicians. The description of the conditions permitting autopsies in the Federal Republic of Germany is followed by a review of the rules governing autopsy practice in the european countries. It is emphasized that the clinical autopsy and its practice should be regulated by a codified law. This law, however, should ensure that the autopsy's objectives may be realized and may indeed contribute to the well-being of the population, to the expansion of scientific knowledge and to the further development of the health care system. PMID- 1604760 TI - [Role of the physician as expert witness]. AB - To work as a medical expert, is also a medical task, although this task produces uneasiness in many physicians. Some reasons are named. The presuppositions for the work as a medical expert are exposed. Proposals are made to improve the qualification of the experts and the quality of the expertises. PMID- 1604761 TI - [Psychiatric-psychologic evaluation of neurotic disorders in the pension process based on a structural-social illness concept]. AB - The psychiatric-psychological judging neurotic disorders is presented under following aspects: the diagnostical guidelines considering international classification systems and the definition of disease given by the jurisdiction. In order to judge the degree of severity of a neurotic disorder with regard to professional fitness this paper proposes Raschs structural social conception of disease. PMID- 1604762 TI - [Somatoform pain and work capacity]. AB - In DSM-III-(R) functional syndromes are introduced, which are partly important for the earning capacity of the afflicted patients. In this paper the somatoform pain disorder is discussed exemplary. According to the DSM-III-R patients with somatoform pain disorder gets typically incapacitated for working. Problems of examination of these patients are reflected in regard of the social insurance pension for patients with traditional neurosis. The construct of the somatoform pain disorder implies not a well-differentiated concept as it existed in the neurosis. Finding out the correct diagnosis depends mainly on the patients self description. Because of this, there are problems to distinguish this disorder from malingering. The estimation of the earning capacity depends mainly on the severity of the disorder, which can be determined analogous to the neurosis. Important social medical aspects (e.g. early recognition) are pointed out. PMID- 1604763 TI - [Does obesity increase mortality? An empirical evaluation of German hospital data]. AB - The vast majority of investigations on the relationship between BMI (body mass index) and mortality results in a U-shaped relationship. Using a randomly selected number of more than 32,000 patients of German acute hospitals the U shaped relationship is confirmed for mortality from cardiovascular diseases. BMI and mortality are not related over wide ranges of BMI for mortality from all causes. Only at the very extremes (heavy overweight and underweight) the number of deaths per number of patients in a certain BMI-class are increased. PMID- 1604764 TI - [Clinical aspects, pathophysiology, therapy and expert evaluation of splenectomy]. AB - Splenectomy increases on principle and for life the risk to die of a foudroyant postsplenectomy infection, the so called OPSI-syndrome. The main factors determining the frequency of the OPSI-syndrome are the age at time of operation and the indication for splenectomy. Postsplenectomy infection is mostly caused by pneumococci. In general the important pathophysiological factors are a lack of filtration capacity, a decreased opsonisation activity and a deficiency of early immunoglobulin production. The increased risk of children is probably caused by a physiologically reduced immune response and a cumulation of primary infections. In the foudroyant course of postsplenectomy infection therapy is mostly taken not in time, and mortality ranges between 50 and 80%. For this reason it is necessary to stress prophylaxis as: antibiotics, vaccination, autotransplantation and preserving surgery. The effectivity and application of these prophylactic measurements are clearly limited. Therefore it is very important to inform all patients and their parents about the low, but lifelong risk of infection following splenectomy in order to begin the antibiotic therapy as soon as possible even in cases of banal infections. In expert opinion about the loss of spleen the real situation of the splenectomized individual has to be regarded in making very precise analysis of the course of disease. This has to be done in considering the branch of insurance ordering the opinion (legal accident insurance, legal pensions insurance, social compensation law, private accident or life insurance). If infections or other illness often appear after splenectomy, these have to recognized as resulting impairment, provided that other causes have been excluded. In uncomplicated course it is not justified to suppose disability only by immanent risk. PMID- 1604765 TI - [Early diagnosis saves human lives--on the status of colorectal tumors]. AB - Colorectal cancers are on rang 3 of the malignant tumors in men and in women in incidence as well as in mortality. The only method to save more patients with these tumors is the early detection. It is to realize at its best by combination of digital rectal examination (DRE), testing for blood in feces and sigmoidoscopy. About DRE nothing is to discuss. The lack of a method without a high percentage of false negative and false positive results is the main problem of testing blood in feces. But the existing methods have to be used until more effective ones will be developed. Method no 3 is the sigmoidoscopy with the new generation of flexible instruments. Doctors have to prefer them because their use is easier, more informative and better tolerable for patients as the old rigid rectoscops. An additional method to evaluate the tumor expansion during surgical treatment is the endoscopic ultrasound examination. It enables the surgeon to look through the colorectal wall for evaluation of the tumor-spreading. There is no doubt, that the surgical treatment is the most effective. It can save around 90% of tumor patients if the tumor is detected in an early stage. The results of chemotherapy are not convincing at all. 5-fluorouracil (5-FU) seems to be the most effective but not curing drug, possibly in combination with immunemodulators. IN CONCLUSION: Colorectal cancer, early detection is the key. If the patient, the practicien and the surgeon will have this in mind, 50,000 pats with colorectal cancer more could be saved this year in the USA. Similar results should be possible in our country also. PMID- 1604766 TI - [Maternity insurance]. PMID- 1604768 TI - Canine hip dysplasia. PMID- 1604769 TI - Biomechanics of the normal and abnormal hip joint. AB - Static analysis of the canine hip has given some insight to the nature and trend of the force and subsequent stress that is normally applied to the joint. Using the static model, the magnitude and direction of force and stress worsens in the hip with the anatomic and stability changes associated with CHD. More sophisticated dynamic models that take into account unbalanced forces and moments with the resultant motion are needed to better understand the mechanics of the hip joint. PMID- 1604767 TI - The pathogenesis of canine hip dysplasia. AB - Dogs with CHD are born with normal hips that subsequently undergo varying degrees of subluxation of the coxofemoral joint. Although the etiology of CHD is multifactorial, the pathogenesis or stages of change within the affected coxofemoral joint(s) are similar regardless of cause. With the onset of the disease, there are progressive structural changes including joint laxity and femoral head subluxation; swelling, stretching, fraying, and eventual rupture of the teres ligament; a shallow, flattened acetabulum, deformity of the head; erosion of articular cartilage, eburnation of subchondral bone, DJD; and periarticular osteophyte formation. PMID- 1604770 TI - The role of nutrition in canine hip dysplasia. AB - The role of nutrition in canine hip dysplasia is a multifactorial as the disease itself. Large and giant breeds primarily are at risk for the disease. Rate of growth, feeding methods, feed consumption, specific nutrients, and electrolyte balances within the diet have all been shown to influence hip dysplasia. Known nutritional risk factors are rapid weight gain and excessive calcium supplementation. Nutritional factors with less secure roles in their influence on the disease process are vitamin C, protein, and carbohydrates. There exists a need to identify further and control the various nutritional factors in the diet that influence canine hip dysplasia. PMID- 1604771 TI - The pathology of canine hip dysplasia. AB - Although the complete pathogenesis of cartilage damage in canine hip dysplasia has not been completely worked out, it appears that joint laxity with resultant excessive stresses upon articular cartilage is the initiating factor. Grossly, this damage is characterized by cartilage thinning with potential exposure of subchondral bone, osteophyte formation, and pannus formation. Microscopically, there is a marked variation in chondrocyte cellularity, with focal regions of hypocellularity and chondrocyte clusters and synovial lining cell hyperplasia and hypertrophy as well as a decrease in proteoglycan content. This latter change has been substantiated biomechanically. Ultrastructural studies indicate that there is extensive alteration of collagen organization within the cartilage. PMID- 1604772 TI - Canine hip dysplasia: clinical signs and physical diagnosis. AB - Clinical signs of hip dysplasia include lameness, gait abnormalities, reluctance to exercise, and pelvic limb muscle atrophy with compensatory shoulder muscle hypertrophy. Because these clinical signs are not pathognomonic for CHD, a thorough orthopedic and neurologic examination is recommended for all patients with suspected CHD. Specific maneuvers, including the Barlow, Ortolani, and Barden's signs are useful to characterize the degree of coxofemoral laxity, both as screening tools in young puppies and as diagnostic aids in clinically lame dogs. None of the signs are definitive diagnostic tests for CHD, but they should be performed as sequential maneuvers in the veterinarian's workup for suspected CHD. Pelvic radiography is mandatory to definitively diagnose CHD but should not be the first step in the workup, because other diagnoses may be missed or concurrent conditions may coexist with dysplasia. PMID- 1604773 TI - Radiographic development of canine hip dysplasia. AB - The radiographic changes observed in the development of CHD in the dog are complex and not fully understood despite years of research. Moderate to severe CHD is relatively easy to diagnose using standard radiographic views and evaluation techniques. However, early detection of mild or borderline CHD continues to be difficult to reliably detect radiographically. Efforts continue to be made to develop new views, techniques, and evaluation methods that will improve the radiographic evaluation of CHD. Until better methods are proven, the standard ventrodorsal leg extended view, evaluated by an experienced reviewer, will remain the method of choice for radiographic detection of CHD. PMID- 1604774 TI - Role of the Orthopedic Foundation for Animals in the control of canine hip dysplasia. AB - The objectives of the Dysplasia Control Registry, the procedure for submitting radiographs, and the radiographic evaluation process are described. The results from the radiographic evaluation of 321,183 dogs are reported by hip phenotypic ratings and breed frequency of canine hip dysplasia. Breeds at risk are documented. Comparison of dogs born between 1981 and 1988 with those born between 1972 and 1980 demonstrated that the frequency of canine hip dysplasia was reduced in 79% of breeds, and the frequency of excellent hips was increased in 88% of the breeds. Reliability of preliminary hip evaluations of dogs under 24 months of age is reported to vary by breed, and the results of 9,161 preliminary evaluations are documented. PMID- 1604775 TI - Conservative and medical management of hip dysplasia. AB - Hip dysplasia has been managed conservatively and medically since the initial description of this disease in 1935. However, little factual information is known about the benefits of the various forms of conservative and medical management. Nonsteroidal anti-inflammatory drugs have been a mainstay of treatment, with the only real debate being which NSAID to use. Only with the recent anecdotal reports of polysulfated glycosaminoglycan has there been any change in medical management of CHD, and this method of treatment warrants further investigation. Conservative and medical management definitely have a role in the treatment of CHD. It must be remembered, however that CHD is primarily a disease of biomechanical alterations and joint laxity, with the cartilage effects being secondary. With a great enough degree of laxity, coxofemoral incongruency, articular damage, or osteoarthritic change, conservative and medical management will not be effective. At that stage, surgical management must be considered. PMID- 1604776 TI - Pectineus tendon surgery for the management of canine hip dysplasia. AB - Pectineus tendonectomy is a useful procedure for relieving pain and rehabilitating the dysplastic dog in select cases. Relief of pain is believed to come from a combination of releasing tension on the hip joint capsule and providing a better loading contact surface on the articular cartilage owing to the increased abduction of the hind legs after surgery. Some pain relief also may come from the release of tension on the pectineus muscle. The modified procedure described in this article results in less seroma formation and less reattachment of the severed ends of the pectineus tendon of origin than the procedure originally described by the author. PMID- 1604777 TI - Three-plane intertrochanteric osteotomy for treatment of early stage hip dysplasia. AB - Indications, preoperative planning, and surgical procedure for the three-plane intertrochanteric osteotomy are described. The goal of this procedure is to decrease the biomechanical stress in the coxofemoral joint, thereby relieving pain associated with early stage canine hip dysplasia. Clinical signs of pain are alleviated for many years. PMID- 1604778 TI - Pelvic osteotomy for axial rotation of the acetabular segment in dogs with hip dysplasia. AB - Pelvic osteotomy has provided normal function and activity to dogs with hip dysplasia. Physical and radiographic examination and palpation under anesthesia permit evaluation of the degenerative process and provide the specific amount of axial rotation of the pelvis necessary for each dog. The technique consists of an osteotomy of the pubis, ischium, and ilium to reestablish acetabular support of the femoral head. PMID- 1604779 TI - Sertl shelf arthroplasty (BOP procedure) in the treatment of canine hip dysplasia. AB - The BOP/Sertl shelf arthroplasty procedure is not difficult or lengthy. It uses minimal metallic fixation. It is quite physiological with minimal morbidity because there is no change in the bony anatomic pelvis except to create an extension of the lateral rim of the acetabulum. The animal is able to walk the day after surgery. The procedure can be performed bilaterally the same day, thus creating good bony stability and decreasing stretching of the joint capsule, which in turn prevents further subluxation and pain in the hip joint. The aim of this procedure is to return the animal to a satisfactory lifestyle through an effective but less complicated surgical procedure as compared to other available options. This procedure is straightforward and can be done by a surgeon who is familiar with orthopedic surgical techniques and has been trained in this procedure. To date, more than 150 veterinarians have had hands-on training to perform this operation. We are not claiming that this procedure is a cure for CHD; rather, it is a procedure that dramatically slows down the progress of this malady and allows the dog to lead a more normal lifestyle and avoids euthanasia. After 51 months, our study of 200 hips has had a success rate of 99% on the animals available for follow-up as evidenced by returning those animals to a satisfactory lifestyle with stable hips. PMID- 1604780 TI - Total hip arthroplasty for treatment of canine hip dysplasia. AB - Cemented THA is an established procedure for treating arthropathies of the hip in large, healthy mature dogs. CHD with secondary osteoarthritis is the most common indication. Although comparative studies between THA and excision arthroplasty have not been reported, our experience with both procedures and studies in the literature support THA as the best available treatment for crippling degenerative joint disease secondary to CHD in large, mature dogs. Negative aspects of the procedure include high cost, the potential of significant complications, and the sophisticated surgical technique required. Improvements in patient selection, design of implants, surgical technique, and postoperative care have decreased the incidence of complications and improved the success rate to over 90%. However, concerns in human applications about cement disease and the desire to increase the functional life of the prosthesis have renewed interest in cementless systems. Advantages of cementless THA are fixation via bony ingrowth and avoidance of problems associated with PMMA. Important technical aspects of cementless THA relate to optimal fit and fill so that the prosthesis is stable, bone ingrowth is promoted, and weight-bearing forces are transferred to the proximal femur physiologically. Problems recognized with cementless systems include fissure fracture, bone resorption, and excessive motion between the implant and bone. Currently, investigations are being conducted to develop prosthetic materials that more closely match the stiffness of bone, stem designs that provide optimal fit and maintain normal strain patterns in the bone, and coating materials that promote permanent fixation by bone ingrowth. Early clinical results in humans and research results in dogs have been encouraging but have not withstood the test of time. Results of cementless techniques must be compared to the standards set by cemented THA over the last 20 years in humans and the last 10 years in dogs. PMID- 1604781 TI - Femoral head and neck excision in the management of canine hip dysplasia. AB - Degenerative joint disease as a sequela to pathology of the coxofemoral joint can cause considerable pain. In dogs weighing less than 20 km, excision of the femoral head and neck is sufficient to control this pain. A pseudoarthrosis functions effectively as a salvage hip joint. In dogs weighing more than 20 km, additional surgery is required to ensure painfree use of the hip. Postoperatively, the weight of these larger animals appears to cause striking of the proximally excised femoral shaft with the pelvis during exercise. This contact causes pain that limits the use of the joint. The inclusion of a biceps femoris muscle sling to prevent this striking and the resultant pain is outlined. PMID- 1604782 TI - Canine hip dysplasia and the breeder. A layman's point of view. AB - Many, though certainly not all, breeders are becoming fairly knowledgeable about CHD and other joint problems. The veterinarian should encourage prevention through selective breeding and lead the client to further understanding of the disorders. Breeders need help in separating scientific evidence from insufficiently tested hypotheses based on testimonials. "Quick-and-easy" cures can be exposed and discounted with just a little search of the literature. The veterinarian's job is similar to that of the teacher in the old one-room country school: some client may have to be taught the basics, whereas those in other stages of progress receive different help. Breeders perhaps need more assistance than do pet owners, because they will affect future generations of dogs. The veterinarian who concentrates on building a trust relationship based on shared facts and a sincere desire to contribute to the well-being of his clients (and his patients) will enjoy a most rewarding relationship with them. PMID- 1604783 TI - Scrapie-like encephalopathy in a greater kudu (Tragelaphus strepsiceros) which had not been fed ruminant-derived protein. AB - A 19-month-old greater kudu (Tragelaphus strepsiceros), whose dam had died 15 months earlier with spongiform encephalopathy, required euthanasia after developing severe ataxia and depression with an apparently sudden onset. No macroscopic abnormalities were detected on post mortem examination but a scrapie like spongiform encephalomyelopathy was apparent on histopathological examination of brain and segments of spinal cord. Negative stain electron microscopy of proteinase K-treated detergent extracts of tissue from the brain stem revealed the presence of scrapie associated fibrils, and a 25 to 28 kDa band comparable with that identified as abnormal PrP (prion protein) from the brains of domestic cattle with spongiform encephalopathy was detected using rabbit antiserum raised against mouse PrP. The animal was born nine months after the statutory ban on the inclusion of ruminant-derived protein in ruminant feeds and, as no other possible sources of the disease were apparent, it appears likely that the infection was acquired from the dam. PMID- 1604784 TI - Acute eosinophilic interstitial pulmonary disease in a pony. AB - An outdoor pony which developed severe respiratory distress in February was shown to have acute interstitial pulmonary disease (alveolitis), which was characterised by a massive exudation of eosinophil rich fluid into the airways. While antibiotic treatment before referral was ineffective, the condition rapidly responded to corticosteroid therapy. No evidence of lungworm was present and it appears that this interstitial pulmonary disease had an immune-mediated aetiology. Bronchoalveolar lavage cytology was of great value in the diagnosis and monitoring of this case. PMID- 1604785 TI - Inheritance of 'overshot' malocclusion in German shorthaired pointers. AB - An abnormality of jaw development in the German shorthaired pointer which results in severe overshot is described. Its frequency of occurrence in a kennel where only phenotypically normal breeding stock were used was six/100 pups alive at three weeks. The abnormality was inherited in a manner consistent with the influence of a single autosomal recessive gene. The penetrance of the gene could possibly be masked in populations in which undershot jaw occurs. PMID- 1604786 TI - Scrapie: a clinical assessment. PMID- 1604787 TI - Streptococcus suis infections in horses and cats. PMID- 1604788 TI - Transport of food animals. PMID- 1604790 TI - Erosion of veterinary influence. PMID- 1604789 TI - Availability of medicines. PMID- 1604792 TI - Treatment of 'watery mouth'. PMID- 1604793 TI - Stabilization of Salmonella-specific dialyzable leukocyte extracts. AB - Activity of Salmonella-specific dialyzable leukocyte extracts (DLE) prepared from mesenteric lymphatic nodes of calves and stabilized with bovine albumin was studied in this work. The effect of ambient temperature and storage period on the activity of DLE was evaluated. Testing for DLE activity by means of capillary leukocyte migration inhibition (LMI) assay showed that DLE stabilized with albumin retained 60% of its activity for 12 months of storage at 4 degrees C. This level of activity was retained in the native DLE (without albumin) kept at 20 degrees C. DLE stabilized with albumin and stored for 12 months at 4 degrees C inhibited the penetration of salmonellae into the liver and spleen, and their colonization in the gastrointestinal tract was significantly reduced. PMID- 1604794 TI - Dialyzable leukocyte extract used in the prevention of Salmonella infection in calves. AB - The protective effect of dialyzable leukocyte extract (DLE) was investigated in the experimental model of Salmonella infection in calves. DLE was obtained from the lymphatic nodes and spleens of fattening bulls immunized with whole-cell Salmonella vaccine (designated DLEs-im), from the same organs of calves immunized and subsequently infected with Salmonella typhimurium (DLEs-inf), and from non immunized fattening bulls (DLEn). Three doses of DLEs-inf and DLEs-im applied intravenously at 3-day intervals induced protection in all calves against infection. There were statistically significant differences in the immunological, clinical and microbiological parameters. Three doses of DLEs-inf injected intramuscularly at 3-day intervals provided a protective effect; however, one calf died. The intravenous application of DLEn induced low protection against experimental Salmonella infection and two calves died. The results indicate that the preparation of antigen-specific DLE may be possible via immunization of fattening bulls. PMID- 1604795 TI - The intestinal and serum humoral immune response of mice to systemically and orally administered antigens in liposomes: I. The response to liposome-entrapped soluble proteins. AB - The development of oral vaccines is of great importance in veterinary medicine and new adjuvants and carriers are essential to this aim. Liposomes are effective systemic adjuvants but the relatively little data on their potential as oral adjuvants is inconclusive. Liposomes containing ovalbumin (OA) were effective adjuvants when administered intraperitoneally to mice. Feeding mice with OA or keyhole limpet haemocyanin in liposomes in a series of priming and boosting regimes failed to elicit any significant increase in serum or intestinal antibody response compared with feeding the free antigen. Oral tolerance induction to systemic challenge was also unaffected by OA entrapment in liposomes. In vitro liposome stability assays at 37 degrees C demonstrated a substantial resistance to disruption in the presence of acidic stomach contents. However, the addition of bile caused a rapid and profound release of protein marker from the liposomes. The rate and degree of disruption was influenced by the type of phospholipid used. These results suggest that liposomes may be useful as carriers for orally administered compounds but they are ineffective as adjuvants for the non particulate, naturally weak immunogens used in this study. PMID- 1604796 TI - MHC class II expression in the bovine mammary gland. AB - The distribution of major histocompatibility complex (MHC) class II positive cells within the connective tissue and the epithelium of the involuted bovine mammary gland has been determined. The effect of intramammary administration of the antigens ovalbumin and formalin killed Streptococcus uberis on the distribution pattern has also been investigated. Infusion of formalin killed S. uberis increased cellular expression of class II antigens when compared with quarters either infused with ovalbumin, not infused at all, or from which minor pathogens had been isolated. The increased expression occurred particularly in the area of the gland cistern-secretory tissue junction. PMID- 1604797 TI - The intestinal and serum humoral immune response of mice to orally administered antigens in liposomes: II. The response to liposome-entrapped bacterial proteins. AB - Effective oral adjuvants are needed to improve the intestinal immune responses to oral vaccines that are based on relatively low molecular weight antigens refined from veterinary pathogens. Liposomes prepared by different methods and composed of phospholipids of varying transition temperature were used to entrap cholera toxin (CT) and fed to mice. No significant increase in the intestinal antibody nor the serum IgA antibody response was detected but levels of serum IgG anti-CT antibody were significantly elevated in the group fed CT in phosphatidylcholine based liposomes. Levels of antibody were significantly reduced in the groups fed CT in dipalmitoylphosphatidylcholine liposomes. Escherichia coli wall extract (ECWE) entrapped in certain liposome types and fed to mice elicited significantly increased serum anti-ECWE antibody responses but intestinal antibody responses were insignificantly different from the controls. These results suggest that orally administered liposomes fail to act as potent intestinal adjuvants for the entrapped antigens of bacterial origin used in this study. PMID- 1604799 TI - A comparison of total and specific immunoglobulin levels in healthy Atlantic salmon (Salmo salar L.) and in salmon naturally infected with Aeromonas salmonicida subsp. achromogenes. AB - Healthy Atlantic salmon and salmon with a history of chronic natural Aeromonas salmonicida subsp. achromogenes infection were compared with respect to total serum protein and the concentration and specificity of serum immunoglobulin. The immunoglobulin level was measured using competitive ELISA and the specific antibody activity against Aeromonas salmonicida subsp. achromogenes was measured using double sandwich ELISA. Significant elevation of serum protein and immunoglobulin concentration was observed in the infected salmon compared with the healthy fish. This was accompanied by weak anti-A. salmonicida activity in the infected fish which seemed to contribute to the raised immunoglobulin level to only a limited degree. PMID- 1604798 TI - Mitogen-induced proliferation of trout kidney leucocytes by one-step culture in fibrin clots. AB - This work describes a trout kidney leucocyte mitogen-stimulation assay using fibrinogen/thrombin. Cloning was obtained by only one step instead of by two steps, as required by the agar method described to date. Cultures were stimulated not only with phytohemagglutinin (PHA) and Escherichia coli lipopolysaccharides (LPS) but also with Concanavalin A (Con A) and six LPS from aquatic pathogenic bacteria. The number of colony-forming cells detected, and their morphological type depended on the mitogen, the time of incubation and the trout. PHA was the best inducer of trout kidney leucocyte colony formation followed by Con A, giving rise to four different homogeneous types of colonies formed by large-nucleated cells, cells with eccentric nuclei, multinucleated cells and lymphocytes. PMID- 1604800 TI - Induction of lymphokine-activated killer cells of equine origin: specificity for equine target cells. AB - The in vitro stimulation of peripheral blood mononuclear cells (PBMC) with interleukin 2 (IL-2) results in the development of potent cytotoxic effector cells, referred to as lymphokine-activated killer (LAK) cells. LAK cells are capable of lysing a wide variety of autologous, allogeneic and xenogeneic tumor cells. The exact mechanism of target cell recognition by LAK cells remains unknown. LAK cell activity has been reported for a variety of domesticated species except the horse. We report here that IL-2-stimulated equine PBMC, which fail to lyse either human or murine tumor cell lines, exhibit potent cytolytic activity against an equine tumor cell line, EqT8888. Cytolytic activity against the EqT8888 cells required 3 days of incubation with IL-2, was mediated primarily by T-cells, and was not restricted by major histocompatibility complex antigens. Though LAK activity could only be demonstrated using equine-derived target cells, xenogeneic targets could be lysed in a lectin-mediated cytotoxicity assay. The xenogeneic targets also failed to block LAK cell-killing of the EqT8888 cells in a cold-target competition assay. These results indicate that LAK cells in the horse appear to utilize a species-specific recognition mechanism during target cell lysis. PMID- 1604801 TI - Evidence of immunosuppression by Demodex canis. AB - Three clinically normal beagles, 3 beagles with localized demodectic mange (LDM), and 3 beagles with generalized demodectic mange (GDM) were investigated simultaneously 1-3 and 4-6 weeks from the appearance of the clinical signs. Blood clinical examination and reactivity of peripheral lymphocytes to Con A and PHA were investigated in the first instance, and reactivity to Con A, PHA, and LPS in the second. Eight aliquots were used in each blastogenesis assay for each dog. All dogs were negative for rheumatoid factor. The results of blastogenesis showed that many observations were distributed non-normally, and that not all dogs in each group responded homogeneously. Comparison of blastogenesis results between dogs demands careful statistical analysis. Responses to mitogens were normal in all dogs at 1-3 weeks except for the LDM dogs that showed an increased response to PHA. Only the response to Con A was moderately inhibited in the LDM dogs at 4 6 weeks. All responses were severely depressed in the GDM dogs at 4-6 weeks. This means that immunosuppression follows rather than precedes the clinical manifestations of GDM, and implies that the phenomenon is induced by the parasite or the host's reaction to it. PMID- 1604802 TI - Induction of tissue eosinophilia by platelet-activating factor in Merino sheep. AB - A study was undertaken on the capacity of platelet-activating factor (PAF) to induce eosinophil accumulation in the mammary glands of non-lactating sheep. Platelet-activating factor induced dose-dependent accumulation of eosinophils in mammary exudates 24 h after infusion. Infection, by intraruminal injection of 20,000 infective Trichostrongylus colubriformis larvae, did not modify the responsiveness of outbred sheep to intramammary infusion of PAF. Mature ewes from high and low responder lines of a flock of sheep, selected on the basis of their responses to vaccination and experimental challenge with T. colubriformis as lambs, did not differ in the magnitude of the eosinophil responses to doses of PAF from 5 x 10(-13) to 5 x 10(-7) mol per gland. Intramammary infusion of an extract from third stage larvae of Haemonchus contortus elicited inflammatory exudates containing five- to ten-fold more eosinophils than that elicited by the highest dose of PAF tested. The experiments indicate that the eosinophil chemotactic agonist PAF can induce tissue eosinophilia in sheep and thus may play a role in directing the accumulation of eosinophils in tissues during disease states such as gastrointestinal parasitism. PMID- 1604803 TI - Equine glomerulonephritis and renal failure associated with complexes of group-C streptococcal antigen and IgG antibody. AB - A 12-year-old thoroughbred gelding died from diffuse global glomerulonephritis, 3 months after a lower respiratory infection from which Streptococcus zooepidemicus was isolated. Immunopathological studies (immunofluorescence, immunodiffusion, immunoperoxidase testing and immunoblotting) indicated the presence of an immune reactant renal disease associated with IgG antibody and streptococcal antigens. PMID- 1604804 TI - LTR sequence and phylogenetic analyses of a newly discovered variant of HTLV-I isolated from the Hagahai of Papua New Guinea. AB - A 631-bp region of the long terminal repeat (LTR) of a variant of human T-cell lymphoma/leukemia virus type I (HTLV-I), isolated from a healthy member of a remote, recently contacted group (Hagahai) in Papua New Guinea, was sequenced and compared to LTR sequences of other members of the primate T-cell lymphoma virus group (PTLV), including HTLV-I, simian T-cell lymphoma virus (STLV-I) and HTLV II. Sequence analysis of the LTR of this New Guinean isolate, designated as HTLV I(PNG-1), indicated a sequence divergence of 8.4% to 10.4% from prototype Japanese HTLV-I(ATK) and other HTLV-I and STLV-I isolates and 48.6% diversity from HTLV-II. Few mutations were found in the core elements of the transcriptional enhancer regions, the TATA box promoter, and the polyadenylation signal and site. Further, the observed changes did not significantly alter the inferred stability of the Rex response element, a stem loop structure critical for polyadenylation and Rex protein binding. Dendograms based on LTR sequences indicated that the strain of virus that evolved into HTLV-I(PNG-1) diverged from the other PTLV in the distant past, just after the progenitors of STLV-I from Asia, but before the ancestors of STLV-I from Africa. By contrast, other HTLV-I isolates were found to represent strains of virus that have diverged more recently and clustered primarily according to their geographical origin. These data confirm that HTLV-I(PNG-1) is a new and distinct variant of the PTLV group. Also, our analyses suggest that both HTLV-I and STLV-I may have originated in the Indo-Malay region and eventually spread to Africa and then to the New World and Japan with horizontal transmission between man and nonhuman primates possibly occurring over thousands of years. PMID- 1604805 TI - Rat cellular mutants for expression of mRNA from the long terminal repeat of murine retrovirus. AB - Previously we isolated revertants from a rat cell line transformed by recombinant murine retrovirus containing the v-src gene. These mutant cell lines, R78 and R107, showed low src-kinase activity, but retained wild-type transforming retrovirus, suggesting that a cellular gene involved in viral gene expression was mutated. Southern and Northern hybridization analyses showed that the expression of viral mRNAs from the integrated proviral DNA was reduced in these mutant cells. DNA transfection experiments with various transforming genes and promoters revealed that the mutant cell lines were resistant to transformation by transforming genes expressed under the long terminal repeat (LTR) of Moloney murine leukemia virus (Mo-MuLV). In contrast, these cell lines could be efficiently transformed by the same transforming genes with human metallothionein promoter, polyomavirus promoter-enhancer, and c-H-ras promoter. Transient expression assays using plasmids containing the CAT gene under the LTR of Mo-MuLV also showed that CAT activity expressed under the LTR in these mutant cells was lower than that in the parental cell line, No. 7. These results suggest that cellular mutations of R78 and R107 cells affect specific transcription from the LTR of Mo-MuLV. Studies using various constructs of the LTR CAT indicated that the region responsible for the repression was located in a fragment (-328 to 150) of the LTR containing the 72-bp repeat enhancer. Somatic cell hybridization experiments showed that the mutant phenotype of these mutant cell lines is dominant to that of the parental cell line. PMID- 1604806 TI - Pathways of viral gene expression during acute neuronal infection with HSV-1. AB - Pathways of viral gene expression were investigated during the acute phase of sensory ganglionic infection with HSV-1. To facilitate these studies we constructed KOS/62-3, an HSV-1 vector in which the Escherichia coli lac-Z gene was inserted behind both copies of the promoter for the viral latency-associated transcripts. Following footpad inoculation of mice with the virus, acutely infected dorsal root ganglion (DRG) neurons were assayed by dual immunofluorescence for the presence of beta-galactosidase and HSV viral antigens. Most infected neurons stained for either beta-galactosidase or viral antigens. Less than 0.2% of neurons staining for viral antigens also expressed beta galactosidase, and less than 10% of neurons expressing beta-galactosidase also stained for viral antigen. As a consequence of these findings, we propose that there are essentially two populations of HSV-infected neurons during the acute phase of ganglionic infection. In one population of neurons there is abundant viral protein synthesis but minimal transcription of latency-associated transcripts, whereas in a second population of neurons viral gene expression is severely restricted except for the synthesis of latency-associated transcripts. Since DRG neurons are a heterogeneous population of cells, we further sought to determine whether either pathway of gene expression was more likely to occur in a particular neuronal phenotype. To accomplish this, antibodies were used to characterize the DRG neuronal phenotypes acutely infected with the virus. The results indicated that the pathway of neuronal infection characterized by transcription of abundant latency-associated transcripts and minimal viral protein synthesis was much more likely to occur in DRG neurons expressing the cellular antigen SSEA-3. These data indicate that the neuron plays a major role in regulating the outcome of infection with HSV. Finally, we sought to determine whether DNA replication occurs in the course of establishment of a latent infection. We found that the DNA content of neurons latently infected with KOS(M) strain HSV was not affected by treatment with nucleotide analogues during the acute phase of ganglionic infection, suggesting that viral DNA replication does not occur during the establishment of latent infection. PMID- 1604807 TI - Functional analysis of biologically distinct genetic variants of simian immunodeficiency virus isolated from a mandrill. AB - We examined the biological properties of two infectious clones of a simian immunodeficiency virus, SIVMND, which were designated as pMD121 and pMD122. Upon transfection into CD4-negative cells, pMD122 generated virions much less efficiently than pMD121. Likewise, the growth kinetics in CD4-positive cells of virus derived from pMD122 were remarkably delayed relative to those of virus from pMD121. The cytocidal activity of the MD122 virus was also low. A series of recombinant clones were constructed from pMD121 and pMD122 to determine the sequence responsible for the low virulence of the MD122 virus. The genetic determinant in pMD122 responsible for its properties was mapped to within a region (316 base pairs) encompassing the tat, rev, and env coding sequences. Sequence analysis revealed that the two clones differed by only one nucleotide in this region. A nucleotide substitution G (pMD121) to T (pMD122) altered an arginine codon to a serine codon in the first tat coding exon. Transient transfection experiments showed that the tat activity of pMD122 was about twofold less than that of pMD121. These findings indicate that small differences in tat activity can have a dramatic effect on the biological behavior of SIVMND. PMID- 1604808 TI - Retained in vitro infectivity and cytopathogenicity of HIV-1 despite truncation of the C-terminal tail of the env gene product. AB - Five in-frame stop mutations in the HIV-1 env gene, which lead to the production of env gene products truncated within the cytoplasmic C-terminal tail, have been generated and their effects on membrane fusion capacity, glycoprotein incorporation into virus particles, infectivity, and cytopathogenicity were analyzed. The resulting truncated glycoproteins were processed normally, were transported to the cell surface, and were able to induce CD4-dependent membrane fusion. The membrane fusion capacity of one of the mutant glycoproteins with a truncation of 144 amino acids was increased to about double of that induced by wild-type glycoprotein. With a single exception, the truncated viral glycoproteins were incorporated into virus particles which were infectious and cytopathic for permissive MT-4 cells. The infection kinetics with the mutated viruses were, however, delayed to varying degrees in comparison to infection with wild-type virus. Nevertheless, in each case, PCR amplification and direct sequencing of viral DNA in the infected cultures confirmed the presence of the mutant and the absence of revertant DNA. The mutant virus encoding a viral glycoprotein with the longest truncation (144 amino acids), in which only 7 cytoplasmic C-terminal amino acids in gp41 remain, resulted in infection kinetics in MT-4 cells which were only marginally delayed in comparison to those induced by wild-type virus. This means that these C-terminal 144 amino acids of gp41 are not necessary for glycoprotein incorporation into virus particles nor do they significantly contribute to the infectivity nor the cytopathogenicity of HIV-1 in MT-4 cells. PMID- 1604809 TI - Lack of direct correlation between p220 cleavage and the shut-off of host translation after poliovirus infection. AB - Poliovirus induces a drastic inhibition of host protein synthesis soon after infection of susceptible cells. The correlation between this inhibition and the cleavage of p220, a polypeptide that forms part of protein synthesis initiation factor elF-4F, has been examined in detail. Measurements of protein synthesis at half-hourly intervals after infection with poliovirus show the lack of direct correlation between p220 cleavage and the blockade of cellular translation. Moreover, the use of inhibitors of poliovirus RNA synthesis helped to dissociate those two events more clearly. Thus, in the presence of guanidine or Ro 09-0179 when little shut-off was induced by poliovirus extensive proteolytic degradation of p220 took place. When HeLa cells infected with poliovirus are placed at 28 degrees the inhibition of host protein synthesis is prevented and cellular translation continues for at least 8 hr, albeit at a reduced level compared to cells incubated at 37 degrees. At 28 degrees, cleavage of p220 is observed and about 80% of p220 is degraded after 6 hr of incubation at that temperature. Strikingly, when cells in which more than 50% of p220 is cleaved are shifted to 37 degrees, cellular translation recuperates to 100%, in spite of the fact that no detectable p220 is present. Furthermore, if poliovirus-infected cells are incubated for 2 hr at 37 degrees to permit the cleavage of p220 and then are shifted to 28 degrees in the presence of guanidine, cellular proteins are synthesized at the same level as uninfected HeLa cells incubated at 28 degrees. These results show that translation of cellular mRNAs takes place in cells containing a cleaved p220 and indicate that this cleavage is not directly responsible for the shut-off of host translation induced by poliovirus. PMID- 1604810 TI - Herpes simplex virus immediate early gene expression in the absence of transinduction by Vmw65 varies during the cell cycle. AB - The requirement for the herpes simplex virus type 1 (HSV-1) protein Vmw65 (VP16) for activation of immediate early (IE) gene expression was examined in synchronized HeLa cells. Analyses of IE RNA levels were conducted during infection with a viral Vmw65 mutant, in1814. The results revealed an increased requirement for Vmw65 when cultures reached G2 phase of the cell cycle. The levels of IE RNAs 1, 2, and 4 were reduced 5-10 times more in G2 than G1/S for in1814-infected cells when compared to cells infected with wild-type virus or 1814R (a rescued virus), and similar but smaller effects were observed on IE RNA 3 levels. The relative decrease at G2 was reversed by resynchronization of cells to G1/S. Mutant in1814 formed plaques less efficiently on cells at G2 than on cells synchronized at G1/S. The results show that, in the absence of functional Vmw65, HSV-1 IE gene expression and replication vary during the cell cycle. PMID- 1604812 TI - Sequence upstream of the 24K protease enhances cleavage of the cowpea mosaic virus B RNA-encoded polyprotein at the junction between the 24K and 87K proteins. AB - To investigate cleavage at the junction between the cowpea mosaic virus (CPMV) 24K and 87K proteins, plasmids were constructed containing the sequence of bottom component (B) RNA encoding the 110K protein plus a variable length of upstream coding sequence. Transcripts derived from these clones were translated in rabbit reticulocyte lysate and the appearance of the 87K protein was used to assess the efficiency of cleavage at the 24K-87K junction. The results show that the 110K protein, containing the contiguous sequence of the 24K and 87K proteins, is stable and that efficient cleavage at 24K-87K junction requires the presence of amino acids upstream of the 24K protease. These observations show that the 170K protein rather than the 110K protein is the precursor of the 87K protein and suggest a mechanism whereby both the B RNA-encoded 110K and 87K proteins can accumulate during infection. PMID- 1604811 TI - Syncytium formation is induced in the murine neuroblastoma cell cultures which produce pathogenic type G proteins of the rabies virus. AB - We investigated comparatively the interactions of host cells with two types of rabies virus G protein, an avirulent type G (Gln) and a virulent type G (Arg) protein, having glutamine and arginine at position 333, respectively. For this purpose, we established four types of cell lines (referred to as G(Gln)-NA, G(Arg)-NA, G(Gln)-BHK, and G(Arg)-BHK cells, respectively) by transfecting either the G(Gln)-cDNA or G(Arg)-cDNA into two kinds of cells, murine neuroblastoma C1300 (clone NA) and nonneuronal BHK-21. Both G(Gln)-NA and G(Arg)-NA cells produced G proteins when they were treated with 5 mM sodium butyrate, but only G(Arg)-NA cells formed syncytia at the neutral pH, which was suppressed by anti-G antiserum. The sodium butyrate-treated G(Arg)-NA cells fused also with sodium butyrate-treated NA cells under coculture conditions, but neither with untreated NA cells nor with BHK-21 cells. On the other hand, both G(Gln)-BHK and G(Arg)-BHK cells constitutively produced G proteins, but no syncytium was produced at the neutral pH. G(Arg)-BHK cells, however, formed syncytia with the sodium butyrate treated NA cells when they were cocultured. These results suggest that only G(Arg) has a potential ability to produce syncytia of NA cells regardless of cell types by which G(Arg) protein was produced and also suggest that a certain cellular factor(s) is required for the syncytium formation, the factor(s) which is lacking in BHK-21 and untreated NA cells but is produced by the sodium butyrate-treated NA cells. PMID- 1604813 TI - Analysis of genetic heterogeneity within the type strain of satellite tobacco mosaic virus reveals variants and a strong bias for G to A substitution mutations. AB - Satellite tobacco mosaic virus (STMV) is a small plant virus that is dependent for its replication on the presence of a helper tobamovirus. RNase protection analysis of genomic RNA of the STMV type strain revealed that it was composed of two major genome types which differed at a single detectable site near nucleotide 753. Analyses of 42 full-length STMV clones for sequence heterogeneity resulted in the identification of 16 variants distinguishable by unique RNase protection assay patterns. Characterization of these variants confirmed the presence of a major heterogeneity site at nucleotide 751 and identified several sites of sequence microheterogeneity typical of an RNA quasispecies population. Mapping of the heterogeneity sites revealed an apparently random distribution along the length of the STMV genome, with no significant clustering or preference for noncoding regions. Infectivity experiments in tobacco showed that RNA transcripts of 13 of the 16 variant clones were infectious, indicating that most of the variants represent functional genomes coexisting in the type strain with the two major genome types. Sequence analyses revealed that most of the heterogeneity sites detected, including the major site of heterogeneity, were single base differences. Assessment of all the heterogeneity sites found in the total of 10,545 nt sequenced allowed us to estimate that the RNase protection assays detected approximately 50% of the differences present in the 16 clones studied. The nature of these differences was highly biased in that 18 of the 29 single base differences characterized (62%) were G to A substitutions. PMID- 1604814 TI - Spliced RNA of woodchuck hepatitis virus. AB - Polymerase chain reaction was used to investigate RNA splicing in liver of woodchucks infected with woodchuck hepatitis virus (WHV). Two spliced species were detected, and the splice junctions were sequenced. The larger spliced RNA has an intron of 1300 nucleotides, and the smaller spliced sequence shows an additional downstream intron of 1104 nucleotides. We did not detect singly spliced sequences from which the smaller intron alone was removed. Control experiments showed that spliced sequences are present in both RNA and DNA in infected liver, showing that the viral reverse transcriptase can use spliced RNA as template. Spliced sequences were detected also in virion DNA prepared from serum. The upstream intron produces a reading frame that fuses the core to the polymerase polypeptide, while the downstream intron causes an inframe deletion in the polymerase open reading frame. Whereas the splicing patterns in WHV are superficially similar to those reported recently in hepatitis B virus, we detected no obvious homology in the coding capacity of spliced RNAs from these two viruses. PMID- 1604815 TI - The interaction of SV40 large T antigen with unspecific double-stranded DNA: an electron microscopic study. AB - T antigen, an early protein encoded by simian virus 40 (SV40), is a specific DNA binding protein with high affinity for elements in the viral origin of replication where it forms a double-hexameric complex as a prerequisite for DNA untwisting and, in the presence of ATP hydrolysis, for DNA unwinding. Like other specific DNA-binding proteins, T antigen also associates with DNA strands of random sequence albeit at reduced affinity. In addition, T antigen is able to unwind unspecific DNA sequences starting from internal binding sites. This property could be a step in the pathway leading to the chromosomal rearrangements that are frequently observed in SV40-transformed cells. This possibility prompted us to investigate the binding of T antigen to unspecific DNA using electron microscopy. We observed that the protein binds randomly to many unspecific DNA sites excluding a preference for particular DNA sequences or structural features. Addition of ATP to the binding buffer induces the formation of oligomeric, possibly hexameric, T antigen complexes that frequently align to form long arrays of DNA-bound protein. Magnesium salts induce the formation of tightly packed T antigen aggregates which bind to DNA to form many DNA branches and loops that emanate from the aggregated protein core. Upon ATP hydrolysis, aggregated T antigen catalyzes the unwinding of DNA duplices. PMID- 1604816 TI - Structure of the L (polymerase) protein gene of sonchus yellow net virus. AB - The complete nucleotide sequence of the L protein gene of sonchus yellow net virus (SYNV), a plant rhabdovirus, was determined by dideoxynucleotide sequencing of cloned cDNAs derived from the negative-strand genomic RNA. The L protein gene is composed of 6401 nucleotides (nt) located between positions 7158 and 13558 relative to the 3' end of the genomic RNA. Sequence analysis suggests that the complementary mRNA contains a 44 nt untranslated 5' leader sequence preceding an open reading frame of 6348 nucleotides that is capable of encoding a polypeptide of 2116 amino acids with a deduced molecular weight of 241,569 Da. The L protein is positively charged, has a high proportion of the amino acids Leu and Ile, and contains putative polymerase and RNA binding domains. Extended alignment of the SYNV L protein amino acid sequence with those of other nonsegmented negative strand RNA virus polymerases reveals conservation of sequences within 12 blocks that appear sequentially along the protein. A cluster dendrogram derived from the L protein alignments indicates that SYNV is more closely related to animal rhabdoviruses than to the paramyxoviruses and that the animal rhabdoviruses have diverged less from each other than from SYNV. PMID- 1604817 TI - The amino acid sequence determination of a granulin and polyhedrin from two baculoviruses infecting Agrotis segetum. AB - The amino acid sequence of Agrotis segetum Granulosis virus (AsGV) granulin and A. Segetum nuclear polyhedrosis virus (AsNPV) polyhedrin was determined by sequencing tryptic and chymotryptic peptides from reduced and carboxymethylated proteins and tryptic fragments of oxidized and maleylated granulin. The comparison of the established peptide structures with the primary structures of other occlusion body proteins from related baculoviruses was also used for the polypeptide chains' reconstruction. The polypeptide chains of AsGV granulin and AsNPV polyhedrin comprise 247 and 246 amino acid residues, respectively. The proteins possess a high percentage of homology in their primary structures (63%). PMID- 1604818 TI - Maturation of Hantaan virus glycoproteins G1 and G2. AB - Hantaan virus-infected Vero E6 cell lysates were used for immunoprecipitation with monoclonal antibodies against glycoprotein G1 (MAbG1) or G2 (MAbG2). When cell lysates were prepared with buffer containing nonionic detergent, both G1 and G2 glycoproteins were precipitated with either MAbG1 or MAbG2. In contrast, when cell lysates were prepared with a buffer containing ionic detergents MAbG1 precipitated only glycoprotein G1 and MAbG2 precipitated only glycoprotein G2. Heterodimers and possibly higher oligomeric forms of the glycoproteins were detected on nonreducing SDS-polyacrylamide gels only after chemical cross-linking and immunoprecipitation with either MAbG1 or MAbG2. In order to determine the sites of Hantaan virus glycoproteins maturation and the G1-G2 complex formation, infected cells were treated with inhibitors that prevent specific steps of oligosaccharide processing. Furthermore, glycoproteins G1 and G2 immunoprecipitated from infected cell lysates or from isolated virus particles were tested for sensitivity to endoglycosidase H, endoglycosidase F, and endoglycosidase D. The results of these experiments show that maturation of both G1 and G2 takes place in the endoplasmic reticulum (ER). Furthermore, G1-G2 complex formation occurs in the ER as well, since the two glycoproteins co precipitated with either MAbG1 or MAbG2 from infected cell lysates treated with brefeldin A and prepared with buffer containing nonionic detergent. PMID- 1604819 TI - A 44,000 glycoprotein is involved in the attachment of echovirus-11 onto susceptible cells. AB - Cellular receptors play an important role in viral pathogenesis. Until now little was known on echovirus (EV) receptor. Using detergent-treated KB cell extracts as immunogen, a mouse monoclonal antibody (Mab 143) was produced that selectively blocks the attachment of EV-11 to KB and other susceptible cells. By immunoblotting, Mab 143 detected a 44,000 protein on susceptible cell lines but not on cell lines from nonprimate origin. The receptor protein complex, purified from KB cell membranes by immunoaffinity using Mab 143 as ligand, was shown to contain a single glycoprotein with apparent molecular weight of 44,000 (gp44). The role of gp44 in the attachment of EV-11 onto KB cells was demonstrated by the ability (i) of affinity-purified gp44 to reduce the infectivity of EV-11 and (ii) of rabbit polyclonal antisera raised against gp44 to protect cells from the replication of various EV, as did Mab 143. PMID- 1604820 TI - Functional classification of simian immunodeficiency virus isolated from a chimpanzee by transactivators. AB - In reporter-based transient expression systems, we characterized simian immunodeficiency virus from a chimpanzee (SIVCPZ), with special reference to the human immunodeficiency virus type 1 (HIV-1). SIVCPZ was not equally activated by tat and rev transactivators derived from representative primate lentiviruses. HIV 1 alone activated SIVCPZ to the full extent in both tat and rev assays. The tat and rev gene products of SIVCPZ, as well as those of HIV-1, efficiently transactivated the other viruses. These results indicate that SIVCPZ is identical to HIV-1 with regard to the compatibility of tat and rev gene activities among four subgroups of primate lentiviruses. PMID- 1604821 TI - Characterization of p30, a highly antigenic membrane and secreted protein of African swine fever virus. AB - We have identified and characterized a 30-kDa phosphoprotein (p30) of African Swine Fever Virus (ASFV) that is synthesized, membrane localized, and released into the culture medium at early times after infection. Sequence analysis of the p30 open reading frame predicts a highly antigenic protein with putative phosphorylation, glycosylation, and membrane attachment sites. PMID- 1604822 TI - Presence of class II histocompatibility DR proteins on the envelope of human immunodeficiency virus demonstrated by FACS analysis. AB - Depending on the cell line used for virus propagation, human immunodeficiency virus (HIV) particles may possess class II MHC proteins, as demonstrated by FACS analysis. HLA-DR appeared in high amounts at the HIV envelope, if the virus was grown in HLA-DR+ cells, but was absent if the virus had been grown in HLA-DR- cells. No other cellular constituents, including HLA-DQ and HLA-DP, were detected in these virions. The presence of HLA-DR in the virion envelope itself in preparations used for diagnostic purposes may explain some of the false-positive results obtained in earlier serological tests for HIV infection. Possible implications of these virus-associated cellular antigens in the immunopathogenesis of AIDS should be considered. PMID- 1604823 TI - Differential accumulation of herpes simplex virus type 1 latency-associated transcripts in sensory and autonomic ganglia. AB - We have analyzed the capacity of sensory and autonomic ganglia to demonstrate latency-associated transcripts (LATs) following inoculation of the anterior chamber of the mouse eye with Herpes simplex virus type 1 (HSV-1). In autonomic ganglia, the number of LAT-containing neurons decreased 50-fold or more from the acute to the latent phase, while in the trigeminal ganglion, the decrease was less than 2-fold. The decrease in autonomic ganglia could not be related to destruction of neurons expressing LATs, since these ganglia harbored substantial amounts of viral DNA. The data demonstrate that during the latent phase of the infection, accumulation of LATs varies depending on the type of infected neuron and suggest that some neurons may harbor a latent infection in the absence of LAT expression. PMID- 1604824 TI - RNA recombination in the genome of barley stripe mosaic virus. AB - Barley stripe mosaic Hordeivirus (BSMV) is a positive-strand RNA virus requiring three single-stranded RNAs (alpha, beta, and gamma) for infectivity. A terminal sequence-dependent cloning strategy was used to clone the entire genome of the CV17 strain. Full-length gamma cDNA clones were obtained when oligonucleotides specific for the 5'-terminal sequence of RNA alpha were used in the cloning procedure, but not when RNA gamma-specific oligonucleotides were used. Sequence analysis of six putative gamma cDNA clones revealed that nucleotides 1-70 possess 89% homology with the first 70 nucleotides of RNA alpha. This leader region is separated from the gamma-specific coding region by an eight-base intervening sequence common to both CV17 RNAs alpha and gamma. Northern and Southern hybridization with oligonucleotide probes specific for either alpha or gamma leader sequences indicated that CV17 gamma cDNA clones are representative of native CV17 gamma RNAs. Furthermore, bioassays indicated that in vitro transcripts derived from these gamma cDNA clones were infectious when coinoculated with in vitro transcripts of full-length alpha and beta cDNA clones. Thus, the evidence suggests that RNA gamma of BSMV strain CV17 is a recombinant molecule which may have arisen as a result of natural recombination between RNAs alpha and gamma. PMID- 1604825 TI - Efficient cell-to-cell movement of beet necrotic yellow vein virus requires 3' proximal genes located on RNA 2. AB - RNA 2 of beet necrotic yellow vein virus (BNYVV) carries six open reading frames. The four 3' proximal frames encode the proteins P42, P13, P15, and P14. The first three species present homologies to proteins encoded by three overlapping open reading frames (the triple gene block) in potexviruses, carlaviruses, and barley stripe mosaic virus. P14 does not display homology with other known plant viral proteins. The functions of P42, P13, P15, and P14 were investigated by site directed mutagenesis. Full-length transcripts of wild-type BNYVV RNAs 1 and 2 were infectious when coinoculated to protoplasts or leaves of Chenopodium quinoa. RNA 2 transcripts in which P42, P13, and P15 were prematurely terminated by frameshift mutations replicated in protoplasts (when inoculated with wild-type RNA 1) but were not infectious to leaves, indicating that the triple gene block proteins of BNYVV are essential for viral cell-to-cell spread. Mutations in P14 were not lethal in leaf infections but smaller local lesions and lesser amounts of viral RNA were produced. RNA 2-related subgenomic RNA species of 2.6, 1.4, and 0.7 kb were detected; they presumably direct synthesis of P42, P13, and P14. No species of the length predicted for a P15-specific subgenomic RNA was detected. PMID- 1604826 TI - Hepatitis B virus C gene promoter is under negative regulation. AB - The regulation of the core promoter of Hepatitis B virus (HBV) was investigated using the chloramphenicol acetyltransferase (CAT) reporter system. Deletional analysis of sequences 5' to the HBV core promoter indicated the presence of a negative regulatory element (NRE) located within a 282-bp BamHI-HincII DNA fragment. The NRE was functional in hepatic as well as nonhepatic cells. Results of in vivo competition experiments suggest a role for cellular transacting repressor protein(s) in the functioning of the NRE. The HBV NRE, positioned 5' to the SV40 early promoter, inhibited the activity of the heterologous promoter in an orientation-independent, but position-dependent manner. These data indicate that the HBV NRE is a silencer element, which functions to downregulate the activity of the core promoter. PMID- 1604827 TI - The light-induced rise in cytosolic calcium starts later than the receptor current of the Limulus ventral photoreceptor. AB - The intracellular arsenazo signal indicating the transient light-evoked change in cytosolic Ca2+ (or Sr2+) concentration was measured in Limulus ventral photoreceptors simultaneously with the receptor current under voltage clamp conditions at 15 degrees C. The latency of the light-evoked arsenazo response was consistently more than 25 msec longer than the latency of the electrical light response (receptor current or -potential). Replacing calcium by strontium in the superfusate caused, within 30-40 min, reversible changes: an enlargement of the arsenazo response and a considerable prolongation of both latencies, that of the electrical and that of the arsenazo response; the difference between the two latencies, however, stayed essentially constant. PMID- 1604828 TI - Electrophysiological correlates of texture segregation in the human visual evoked potential. AB - We investigated whether the visual evoked potential (VEP) reflects cortical processing associated with preattentive texture segregation. On a visual display unit we presented stimuli with various arrangements of oriented line segments that either led to the appearance of a "preattentive" checkerboard or did not. Two presentation modes were used (pattern onset at 1 Hz and rapid pattern change at 4.3 Hz), while luminance (57 cd/m2) and contrast (92%) of the line segments remained constant. VEPs were recorded in 7 human subjects. The VEP was analyzed as a linear combination of putative components, which are evoked by either local pattern, quasi-local orientation contrast or global preattentive structure. In the transient VEP, we found a negativity over the posterior pole at a latency between 161 and 225 msec (FWHM) in the linear combination designed to extract segregation-specific components. Peak amplitude reached 3.1 +/- 0.8 microV (mean +/- SEM) at 199 msec. This negative peak appeared only for textures containing orientation contrast. Steady-state analysis of the rapid presentation also revealed a significant component (P = 0.002) associated with texture segregation. These potentials either represent processing of orientation contrast or global processing of texture segregation. The results suggest that specific surface potentials, differing from cognitive potentials, can be derived which are associated with preattentive processing. PMID- 1604829 TI - Study of retinal dystrophy in RCS rats: a comparison of Mg-ATP dependent light scattering activity and ERG b-wave. AB - A comparative study using the techniques of ERG to measure the b-wave and light scattering relaxation spectrophotometry (LSRS) to determine the dynamic behavior Mg-ATP dependent processes in the rod photoreceptors of pigmented control and dystrophic RCS rats has been carried out. LSRS results, based exclusively on photoreceptor rod outer segment dynamics, suggest a progressive failure in the dark and light-induced Mg-ATP dependent processes as a function of age. The dark signal amplitude in the dystrophic rats decreases to about 50% of the control by 5 weeks post-natal; the light-induced signal has decreased by 30% in the same period. The ERG b-wave results indicate that the differences in the amplitude and the time required to attain the peak amplitude become increasingly pronounced between the control and dystrophic groups of rats again as a function of age. By 10 weeks of age, the intensity of light required to obtain a b-wave with a amplitude of 100 microM is 10(3) greater in the dystrophic RCS rats. Similarly, the time to achieve this peak increases in the dystrophs with age. These results indicate that the retinal dystrophy in the RCS rat affects the activity of the rod photoreceptor cells. PMID- 1604830 TI - The field topography of ERG components in man--I. The photopic luminance response. AB - A technique of multi-input systems analysis is used to explore the field topography of ERG responses to local luminance modulation. Variations in amplitude and wave form are studied within the central 23 degrees. Outside the fovea, the amplitude appears to follow a simple power law rx as a function of eccentricity r where x is approximately -2/3. The largest inter-subject variability is found in the fovea. Some nasal-temporal asymmetry is observed in all subjects with higher response densities in the temporal field outside the blind spot. The topography of the luminance response shares all these properties with the density of retinal cones. PMID- 1604831 TI - Electrical responses to short-range kinematogram displays: an occipital lobe global motion process in humans? PMID- 1604832 TI - Nonconjugate adaptation of human saccades to anisometropic spectacles: meridian specificity. AB - Recently it has been demonstrated that saccades become different in size in the two eyes if a subject is adapted to anisometropic spectacles, which provide visual images of different magnitude to the two eyes. These nonconjugate adaptations adequately meet the requirements of those spectacles and, once acquired, they persist (with some reduction) even during monocular viewing. We now demonstrate that such nonconjugate adaptations of saccades can be meridian specific, if there is a pressure for such meridian-specificity. This pressure was provided by means of a cylindrical spectacle-lens. Adaptations along a vertical, horizontal or oblique meridian did not transfer to the orthogonal meridian. These results demonstrate a capability of saccadic adaptation to deal with calibration problems restricted not only to one eye, but even to one specific plane of muscular action. Our results also suggest that the meridian-specific adaptations of oblique saccades take place at a stage before the decomposition of motor commands into separate horizontal and vertical components. The meridian-specific nonconjugacies were also expressed in smooth-pursuit eye movements. Post-saccadic drift adapted only along the horizontal meridian. PMID- 1604833 TI - Motion coherency rules are form-cue invariant. AB - Object features can be made manifest by differences in a variety of physical attributes or figural cues. In this study we provide evidence that motion signals arising from different figural cues can be combined to produce a percept of a coherently moving (heterogeneous-cue) pattern. Moreover, as is true for homogeneous-cue patterns, similarity along the dimensions of contrast (we introduce the idea of contrast equivalence) and spatial frequency determines whether coherent motion is perceived. These results are in accordance with recent physiological evidence demonstrating that directional selectivity of many neurons in cortical visual area MT is invariant over changes in the figural cue that defines the moving stimulus ("form-cue invariance"). PMID- 1604834 TI - Color vision in the California sea lion (Zalophus californianus). AB - Three California sea lions were trained to discriminate between a colored stimulus and two shades of gray in a 3-fold simultaneous choice situation. The colors blue, green and red were tested against shades of gray varying from low to high relative brightness. All animals distinguished blue from gray; two animals also distinguished green from gray; but none discriminated between red and gray. Our data suggest that California sea lions have dichromatic color vision. Their ability to discriminate colors in the blue-green part of the spectrum could be a physiological adaptation to their aquatic coastal habitat. PMID- 1604835 TI - Absence of smooth motion perception in color vision. AB - We have tested the behavioral evidence for a separation of the processing of color contrast from motion in the human visual system. Two different aspects of motion perception are examined; the identification of the direction of movement of a chromatic grating and the perception of smooth motion. The results show that color vision is at no great disadvantage in the identification of direction of movement, since this can be done at color contrasts quite close to detection threshold over a wide range of spatial and temporal frequencies. However, we find that subjects can identify direction without having the genuine perception of smooth motion. Smooth motion perception is revealed to be highly impaired since it is detected only at very high color contrasts and over a narrow range of spatial temporal conditions. PMID- 1604836 TI - Disconjugate ocular motor adaptation in rhesus monkey. AB - We report a model for inducing disconjugate, orbital-position dependent, ocular motor adaptation in the rhesus monkey. Animals wore a combination of laterally displacing prisms placed in front of one eye calling for a discrete change in ocular alignment when the eyes reached particular orbital positions. After wearing the prism combination the animals developed adaptive changes both in static alignment during fixation and in dynamic alignment during eye movements. These changes persisted with only one eye viewing and so became independent of the immediate presence of disparity cues. There were, however, imperfections in the adaptive responses; the changes in the innervation were gradual across the prism edge, not abrupt as required. This finding may reflect inherent limitations in the capability for disconjugate adaptation. PMID- 1604837 TI - Shape analysis and stereopsis for human depth perception. AB - The perceived relative depth of two isolated short parallel lines in the center of a scene is known to depend on the disparities and positions of other items in the scene, as well as on their own disparities. We demonstrate here that the shapes of these other items also contribute significantly to the perceived depth, and that these non-disparity influences on depth judgements may already be evident when only three dots are presented as stimuli. When two short vertical test lines are surrounded by a trapezoidal "picture frame", the perceived relative depth of the test lines is affected by the shape of the trapezoid as well as by the disparities assigned to its vertical parallel sides. The influence of the trapezoidal frame can be interpreted as an effect of perspective. The induced relative depth of the test lines is measured by recording the amount of "compensating disparity" that must be given to one of the lines in order for observers to judge the two test lines to be equidistant from the observer's viewing position. Surprisingly, for fixed disparities of the vertical edges of the surrounding picture frame, the induced depth of the test lines increases as the difference in the lengths of the vertical sides increases, regardless of whether the perspective interpretation of the difference in the lengths is consistent with or in conflict with the disparity-defined slant. Shape-related apparent depth changes are especially sensitive to the shape of the trapezoid if it is nearly rectangular, and are comparable in magnitude to those resulting from changes in disparity of the surrounding frame. When a pair of short vertical parallel test lines is presented alone, without a surrounding frame or any other items in the scene, excellent relative depth discrimination is displayed by most subjects. However, if the lines are replaced by squares, trapezoids, triangles, single horizontal lines, or other figures of about the same size as the original test lines, the slant discrimination threshold for these plane figures for naive observers become poorer by a factor of 20-100. By the use of a feedback signal, observers can be trained to use only disparity cues and ignore shape effects. Some observers have difficulty ignoring the shapes of some figures, the "difficult" figures being different for each observer. After training, the relative depth thresholds for most figures approach those of the original unconnected parallel test lines. PMID- 1604838 TI - Spatial localization without visual references. AB - To explain the veridical percept of the spatial ordering of objects and the generation of eye movements to peripheral targets, Lotze (1885 Microcosmos. Edinburgh: T. & T. Clark) proposed that there is a position label (local sign) for each retinal element. To estimate the precision of local sign information, we measured absolute localization thresholds at various eccentricities in the nasal visual field, in the complete absence of visual references. To eliminate perception of the visual surround, observers viewed a large display screen through a neutral density filter (2.0 log unit) in a dark room. The fixation target was extinguished at various times (interstimulus intervals or ISIs) prior to the onset of the test stimulus. In general, our results show that localization thresholds are proportional to the target eccentricity at all ISIs. At each eccentricity, localization thresholds are elevated after the extinction of the visual reference compared to thresholds when the reference is present. However, relative to the referenced threshold, unreferenced thresholds are elevated by a greater proportion at smaller eccentricities than at larger eccentricities. Our threshold vs ISI data can be adequately modeled on the basis of an intrinsic positional uncertainty, which increases with eccentricity, and additive and multiplicative sources of noise. The additive noise appears to reflect primarily the increasing scatter in eye position when the fixation target is extinguished. Our model's estimate of intrinsic positional uncertainty in the isoeccentric direction appears to reflect primarily the intrinsic positional uncertainty of the peripheral retina (the local sign), being very similar to cumulative cone position uncertainty and to the spacing between ON-P beta ganglion cells. In the isoeccentric direction, the estimated precision of the local sign mechanism across eccentricities is slightly better than the precision of saccadic endpoints, suggesting that noise in the motor system must also contribute to the scatter of saccadic endpoints in the isoeccentric direction. Interestingly, in the radial direction, we find a surprising similarity in our observers' positional uncertainty and the precision of saccadic endpoints. PMID- 1604839 TI - Depth capture and transparency of regions bounded by illusory and chromatic contours. AB - Spillmann and Redies noted that when a transparent textured pattern is held above the Ehrenstein figure, the subjective surfaces appear to lie not in the plane of the figures but in the plane of the overlying texture. In Experiment 1, we tested this phenomenon with chromatic squares and found that the perceived depth of regions bounded by the chromatic contours was captured by overlying texture planes when the square was equiluminous with the background. We then tested this phenomenon with a variety of illusory contour stimuli and found that it only occurs with figures involving fine line terminators, and not, for example, with the solid Kanizsa triangle. These results suggest that chromatic contours and the illusory contours induced by line terminators provide only weak binocular disparity signals and that these signals are easily overwhelmed by the disparity signals from the overlying luminance texture. PMID- 1604840 TI - Brightness matching and flicker photometric data obtained over the full mesopic range. AB - Three normal observers made visual matches from 0.03 to 100 td on a 10 degree central field at 445, 560 and 630 nm, using two different methods: heterochromatic flicker photometry and direct comparison brightness matching. In a relative sensitivity vs illuminance plot, the brightness matches underwent smooth changes, while the flicker curve exhibited a step-like transition around 1 td, between two separate branches. A reverse Purkinje shift was found on the high mesopic branch at 630 nm, possibly due to cone-cone interactions, and on the low mesopic branch at 445 nm, with questionable origin. At 630 nm and 0.03 td, both methods yielded matches that were not truly scotopic but might not have addressed the same mechanisms. PMID- 1604841 TI - Directional asymmetry of the frog monocular optokinetic nystagmus: cholinergic modulation. AB - The frog monocular optokinetic gaze nystagmus (OKN) was studied by coil recordings after intravitreal administration of cholinergic drugs into the closed eye. Before injection, the frog displayed OKN for stimulations in the temporo nasal (T-N) direction only. The injection of muscarinic agonists, as well as that of nicotinic antagonists, provoked the appearance of a naso-temporal (N-T) component, the slow phase velocity gain then being strongly and significantly increased. The abolition of the OKN directional asymmetry indicates that acetylcholine seems to act in opposite ways through muscarinic and nicotinic binding sites. The GABAergic and cholinergic systems may interact to generate and modulate OKN in the frog. PMID- 1604842 TI - Spatial frequency mechanisms with short-wavelength-sensitive cone inputs. AB - We have estimated the minimum number and frequency tuning of spatial mechanisms with Short-Wavelength-Sensitive (SWS)-cone inputs. This was accomplished by isolating SWS cones with intense, long-wavelength (yellow) adaptation, and measuring threshold elevation functions for short-wavelength, spatially localized test stimuli masked by obliquely oriented, short-wavelength, cosine gratings. Peak spatial frequency of the cosine gratings and test stimuli varied from 0.25 to 2.83 cpd in 0.5 octave steps. Results derived in this manner demonstrate that SWS cones input to at least two orientation selective mechanisms with peak spatial frequencies of approx. 0.7 and 1.4 cpd, respectively. The frequency tuning of the isolated-SWS-cone, spatial frequency mechanisms resemble closely the lowest two mechanisms measured with luminance modulation (i.e. normal viewing conditions where all cones contribute to the response). PMID- 1604843 TI - Spatial frequency selective mechanisms underlying the motion aftereffect. AB - The motion aftereffect (MAE) was used to study the spatial frequency selectivity of suprathreshold motion perception. Observers were adapted to drifting sine-wave gratings confined to a retinal eccentricity of approx. 4 deg. The magnitude of the subsequent MAE was measured while viewing a stationary sine-wave grating test surface of one of a number of spatial frequencies. The largest MAE was found when the spatial frequency of the test stimulus was the same as that of the adapting stimulus. This phenomenon held for spatial frequencies between 0.5 and 4 c/deg, and was robust with changes in contrast of either adapting or test gratings. However, at an adapting spatial frequency of 0.25 c/deg, the peak MAE was observed at 0.5 c/deg. Control experiments indicated that this peak shift was not the result of the reduced number of cycles in the stimulus, nor the temporal frequency. There was no measurable MAE at spatial frequencies lower than 0.25 c/deg. These results suggest the existence of a "lowest adaptable channel" for the motion aftereffect. PMID- 1604844 TI - Changes in vestibulo-ocular reflex (VOR) anticipate changes in vergence angle in monkey. AB - The axis of head rotation is usually different from the axis of eye rotation. Geometrical considerations show that the eyes translate with respect to visual targets located near the head. In order to accurately stabilize retinal images against this translation, the vestibulo-ocular reflex (VOR) must be modulated inversely with the target's distance. The neural correlate of viewing distance used to modulate the VOR is not known. Since vergence angle is related inversely to viewing distance, an efference copy of instantaneous vergence angle or proprioceptive afferent information from extraocular muscles could be used to adjust the VOR. To examine this hypothesis, we compared the time-course of changes in the VOR with the time-course of changes in vergence angle. The VOR was induced by briefly rotating monkeys about a vertical axis at different times during the execution of vergence eye movements. We found that the amplitude of the VOR changed systematically during the course of a vergence eye movement. On average, the changes in the amplitude of vestibular induced eye movements anticipated changes in vergence angle by 50 msec, but in some instances, up to 200 msec of anticipation was observed. These data suggest that a central command signal rather than an afferent or efferent copy of vergence eye position was used to modulate the VOR. PMID- 1604845 TI - Reduction of foveal desensitization with blurred backgrounds. AB - Photopic spatial desensitization and sensitization (Westheimer) functions were measured with sharp edged and blurred edged backgrounds. Data show that for 6-min backgrounds, desensitization is reduced for test flashes presented against blurred backgrounds compared to test flashes presented against backgrounds with sharp edges. We suggest that the transients from edges of retinal images, caused by high frequency fixational eye movements, contribute to the mechanisms of spatial desensitization and sensitization; the effect of transients is reduced by blurring the backgrounds. PMID- 1604846 TI - Retinoscopic measurement of the refractive state of the rat. AB - Using retinoscopy, we measured the refractive state of 96 eyes of three different strains of rats: albino Sprague-Dawley, Royal College of Surgeons (RCS) with and without inherited retinal dystrophy, and lean and obese varieties of Zucker rats. Contrary to previous reports, we do not find consistent high hyperopia in the rat, but rather refractions that range from near emmetropia (-0.12 D) to extreme hyperopia (+18.95 D). This range of refractive errors suggests a poorly developed emmetropization mechanism in the rat, and that individual refractions should be performed on animals utilized in experiments where refractive state is critical. PMID- 1604847 TI - Retinal speed gradients and the perception of surface slant. AB - Previous work has demonstrated a difference in human sensitivity to compressive and shearing speed gradients. This raises the possibility that the ability to estimate the slant of a surface may vary with its direction of tilt. No such variance was found here, which may indicate that slant estimation depends upon deformation rather than upon compression or shear. PMID- 1604848 TI - Rapid reorganization of cortical maps in adult cats following restricted deafferentation in retina. AB - The retinotopic map in the visual cortex of adult mammals can reorganize in response to a small injury in a restricted region of retina. Although the mechanisms underlying this neural plasticity in adults are not well understood, it is possible that rapid, adaptive alterations in the effectiveness of existing connections play a key role in the reorganization of cortical topography following peripheral deafferentation. In order to test this hypothesis, a small retinal lesion was made in one eye of adult cats and the visual cortex was mapped before and immediately after enucleating the non-lesioned eye. We found that substantial reorganization takes place within hours of enucleation. PMID- 1604849 TI - Texture segregation is processed by primary visual cortex in man and monkey. Evidence from VEP experiments. AB - We investigated whether the process of texture segregation can be allocated to a specific visual cortical area. We designed a stimulus to reveal the presence of a mechanism, which is specifically sensitive to a checkerboard, that is solely defined by textures segregating due to orientation differences of the constituting line segments. We recorded evoked potentials to this stimulus in man and awake monkey. A difference component, signalling texture segregation sensitivity, could be recorded from both types of subjects. Its presence depended on the spatial extent of the textures, in a manner correlating with the perceptibility of the checkerboard. This difference response could be localized in primary visual cortex by means of equivalent dipole estimations. PMID- 1604850 TI - Effects of colour substitutions upon motion detection in spatially random patterns. AB - To investigate the effects of colour upon motion detection, the short-range motion displacement limit (Dmax) was determined using two-frame kinematograms in which the two classes of square comprising the pattern differed both in luminance and in colour. In the second motion frame, the squares retained either the same luminance and colour as in the first frame, or they changed their colour while retaining their luminance. The experiment was repeated at three different viewing distances to investigate the effects of element angular size. Two of the four observers had normal trichromatic colour vision; the other two were dichromats (protanopes). For the trichromatic observers, the change of colour between frames made motion displacements harder to detect when the squares were large, but not when they were small. The result accords with an input of colour into motion detection at low but not at high spatial frequencies. For the dichromats, the colour change had little effect at any of the viewing distances, thus ruling out the possibility that the deleterious effects of colour substitution upon motion detection in trichromats was due to chromatic aberration or other artefacts. PMID- 1604851 TI - The influence of chromatic aberration on the static accommodative response. AB - Previous measurements of static accommodation have consistently shown steady state errors over most of the range; the response lags below the stimulus and, at low levels, the response leads the stimulus. A series of experiments is presented in which the longitudinal and, for the first time, transverse chromatic aberrations of the eye were varied and the resultant stimulus-response functions of accommodation were measured. The results show that the steady state error of accommodation is not influenced by manipulations of the magnitude or the direction of either longitudinal or transverse chromatic aberration. This indicates that a particular wavelength is not preferentially focussed on the retina as a function of stimulus level and supports the negative feedback theory of accommodation. PMID- 1604852 TI - Normal development of refractive state and ocular component dimensions in the tree shrew (Tupaia belangeri). AB - The normal development of refractive state, ocular components and simple visually guided behaviors was examined in maternally-reared tree shrews. Six groups consisting of 5 animals each were anesthetized and examined after 0, 15, 30, 45, 60 and 75 days of normal binocular visual exposure. Measures in the 75-day group provided values for an improved schematic eye of the tree shrew. Cycloplegic refraction showed a marked hyperopia (+25 D) at eye opening which decreased rapidly during the first 15 days of visual exposure and stabilized near the value (+5 D) expected in an eye of this axial length (approx. 7.8 mm). Corneal radius increased slightly during development. Anterior segment depth, measured by A-scan ultrasonography, seemed to complete most of its development at an earlier age (15 30 days of visual exposure) than did other ocular parameters. Lens thickness increased steadily throughout development. Vitreous chamber depth increased rapidly until 15 days of visual exposure, and then decreased because the lens thickness increased more rapidly than axial length. Crude orienting to, and following of, large objects developed shortly after eye opening (median age at onset, 5 and 6 days, respectively). Triggered visual placing responses developed at about the same time that the refractive state completed the rapid drop from highly hyperopic values. The slowed rate of ocular development after 15 days of visual exposure may be related to increased retinal activity that is permitted by neural maturation and by the presence of a relatively well-focussed retinal image. The increased activity may influence the final dimensions of the eye to coordinate the axial length with the focal length of the eye. PMID- 1604853 TI - The development of experimental myopia and ocular component dimensions in monocularly lid-sutured tree shrews (Tupaia belangeri) AB - Tree shrews were monocularly deprived (MD) from the day of eye opening for periods of 15, 30, 45, 60 and 75 days. The initial structural change after 15 days of MD was a flattening of the corneal curvature in the deprived eye causing a hyperopic increase in refraction, relative to the fellow control eye. A relative myopia was first observed after 30 days of deprivation and increased as the length of MD increased. Animals monocularly deprived for 75 days consistently showed high degrees of myopia (greater -10 D). An increase in vitreous chamber depth was found after 30 days of deprivation and continued to increase, relative to the control eye, throughout the developmental period under investigation. There was a strong correlation (r = 0.84) between increase in vitreous chamber depth and the amount of experimentally-induced myopia. Anterior chamber depth was shallower in the deprived eyes of all animals. The crystalline lens was also consistently thinner in the deprived eye. Based on optical modeling, the observed myopia was consistent with the changes in ocular component dimensions. The susceptible period for experimental myopia begins about 15 days after eye opening. PMID- 1604854 TI - Noise and the absolute thresholds of cone and rod vision. AB - Literature data on light detection by cone and rod vision at absolute threshold are analysed in order (1) to decide whether the threshold performance of dark adapted cone vision can, like that of rod vision, be consistently explained as limited by noise from a "dark light"; (2) to obtain comparable estimates of the dark noise and dark light of (foveal) cones and (peripheral) rods. The dark noise was estimated by a maximum-likelihood procedure from frequency-of-seeing data and compared with the dark light derived from increment-threshold functions. In both cone and rod vision, the estimated dark noise coincides with Poisson fluctuations of the estimated dark light if 17% (best estimate) of lambda max-quanta incident at the cornea produce excitations. At that fraction of quanta exciting, dark lights are equivalent to 112 isomerisations per sec in each foveal cone and 0.011 isomerisations per sec in each rod. It is concluded that (1) the threshold performance of dark-adapted cone as well as rod vision can be consistently described as noise-limited, but not by postulating a multi-quantum coincidence requirement for single receptors; (2) the underlying intrinsic activity in both the cone and the rod system is light-like as regards correspondence between noise effect and background adaptation effect. One possibility is that this activity is largely composed of events identical to the single-photon response, originating in the visual pigment, in cones as well as in rods. PMID- 1604855 TI - The relationship between cone pigments and behavioural sensitivity in a New World monkey (Callithrix jacchus jacchus). AB - Microspectrophotometric measurements of visual pigments and behavioural measurements of spectral sensitivity are reported for individual marmosets from 3 family groups. The sex differences and polymorphism that characterise the long wave cone pigments in this species are well reflected by variations in the behavioural sensitivities. With one exception, the pattern of inheritance is compatible with a genetic model in which the long-wave pigment is specified by a single polymorphic locus on the X-chromosome. Measurements are also reported for the spectral absorbance of the marmoset lens, and these are used to reconstruct short-wave behavioural sensitivity from the microspectrophotometric measurements of the short-wave cones. PMID- 1604856 TI - The ratio of L cones to M cones in the human parafoveal retina. AB - We present psychophysically-based estimates of the relative numbers of long wavelength-sensitive (L) and middle-wavelength-sensitive (M) cones in the parafovea of three color-normal trichromats. Using methods previously applied to the fovea centralis, we obtained estimates of the relative numbers of L and M cones at retinal eccentricities of 1.0, 1.5, 2.0, 3.0, and 4.0 deg along the horizontal meridian of the temporal retina. Results for three observers indicate that the L to M cone ratio remains approximately invariant from the fovea to 4.0 deg eccentricity, with a mean ratio near 2:1. PMID- 1604857 TI - An algorithm separating saccadic from nonsaccadic eye movements automatically by use of the acceleration signal. AB - An algorithm is described to discriminate automatically between saccades and slow eye movements. Sampled data of the eye position have been used to calculate the momentary acceleration of the eye. The higher acceleration values of the saccadic eye movements as opposed to the slow compensatory or pursuit eye movements served to differentiate between the two. The method is demonstrated by search-coil data in squirrel monkeys. PMID- 1604858 TI - Reading without saccadic eye movements. AB - To assess the limitation on reading speed imposed by saccadic eye movements, we measured reading speed in 13 normally-sighted observers using two modes of text presentations: PAGE text which presents an entire passage conventionally in static, paragraph format, and rapid serial visual presentation (RSVP) which presents text sequentially, one word at a time at the same location in the visual field. In Expt 1, subjects read PAGE and RSVP text orally across a wide range of letter sizes (2X to 32X single-letter acuity) and reading speed was computed from the number of correct words read per minute. Reading speeds were consistently faster for RSVP compared to PAGE text at all letter sizes tested. The average speeds for text of an intermediate letter size (8X acuity) were 1171 words/min for RSVP and 303 words/min for PAGE text. In Expt 2 subjects read PAGE and RSVP text silently and a multiple-choice comprehension test was administered after each passage. All subjects continued to read RSVP text faster, and 6 subjects read at the maximum testable rate (1652 words/min) with at least 75% correct on the comprehension tests. Experiment 3 assessed the minimum word exposure time required for decoding text using RSVP to minimize potential delays due to saccadic eye movement control. Successive words were presented for a fixed duration (word duration) with a blank interval (ISI) between words. The minimum word duration required for accurate oral reading averaged 69.4 msec and was not reduced by increasing ISI. We interpret these results as an indication that the programming and execution of saccadic eye movements impose an upper limit on conventional reading speed. PMID- 1604859 TI - The development of the temporal and nasal visual fields during infancy. AB - We used static perimetry to measure the development of the monocular visual field during infancy. Infants from birth to 6 months of age, and adults, were shown a 3 or 6 degrees flashing light at various locations between 15 and 120 degrees in the temporal and nasal visual fields. We assumed that subjects could see a light if they moved their eyes toward it more often than they looked in the same direction on blank control trials. For both the 3 and 6 degrees lights, the visual field expanded with age from the center out, and development in the nasal visual field lagged behind development in the temporal visual field. Possible reasons for these findings are discussed. PMID- 1604860 TI - Color induction via non-opponent lateral interactions in the human retina. AB - Retinal connections causing colors in Benham's top (pattern induced flicker colors, PIFCs) are investigated by psychophysical experiments. PIFCs are still seen when stimuli to different cones are demodulated selectively, indicating the involvement of non-opponent channels. PIFCs also occur on retinal areas next to those affected by modulated stimuli; further, both monochromat and dark-adapted trichromats perceive PIFCs which are achromatic. These additional findings point to horizontal cells as neuronal mediators of modulated excitation leading to PIFCs. The unspecifity of the postulated connection with respect to cone types agrees with anatomic findings of Boycott, B. B., Hopkins, J. M. and Sperling, H. G. (1987, Proceedings of the Royal Society of London, B, 229, 345-379) on horizontal cells. PMID- 1604861 TI - Accommodative hysteresis as a function of target--dark focus separation. AB - The concept of dark focus (DF) as fulcrum for accommodative effort was examined by inducing adaptation of tonic accommodation with the target at varying dioptric distances from the DF. Mean pre- to post-changes in DF at the initial post fixation test essentially were linear (r2 = 0.975), with zero intercept, with respect to the target-DF separation, as were the data of most individual subjects. Target-DF distance thus is a major determinant of adaptation of tonic accommodation. These results are consistent with the interpretation of DF as a zero reference point or fulcrum about which accommodative effort varies. PMID- 1604862 TI - The human visual system averages speed information. AB - It has been known for many years that human observers are unable to detect modest accelerations and decelerations in moving visual stimuli. We find that human observers can integrate speeds over many dots, moving at different speeds, producing a global speed percept analogous to the global direction percept first reported by Williams, D. W. and Sekuler, R. (1984, Vision Research, 24, 55-62). We measured speed discrimination for random dot stimuli which contained many different speeds. Our results show that observers always base their discrimination on the mean speed of the stimulus; changes in other stimulus characteristics (e.g. mode) are not detected. Moreover, discrimination thresholds for the global mean speed derived from many different speeds are comparable to those obtained with stimuli in which all dots move at the same speed suggesting that the internal noise associated with the encoding of speed information is quite high. PMID- 1604863 TI - Visual persistence of figures defined by relative motion. AB - In order to measure visual persistence of figures that were solely defined by relative motion (motion-defined figures or motion figures), random-dot kinematograms were used to form stimulus figures in the two-frame, missing element task introduced by Di Lollo, V. (1977 Nature, 257, 241-243). Experiment 1 showed that motion-defined figures persisted for about 130 msec after the termination of the stimulus presentation (i.e. after the dots stopped moving). This was similar to but several tens of milliseconds longer than the visual persistence of figures which were defined by a luminance difference (luminance defined figures or luminance figures) in the same random-dot pattern. Since motion detectors are not found in the retina or lateral geniculate in primates, our results strongly suggest that visual persistence is not only a retinal phenomenon but also a cortical one. Experiment 2 investigated the possible influence of motion aftereffects on the visual persistence of motion figures. The results showed that coherent movement of the dots over the whole display after the stimulus offset did not reduce the visual persistence of motion figures, suggesting that the source of this persistence is not a motion aftereffect. In Experiment 3, visual persistence for the motion-defined figures was shown to be longer than that for luminance-defined figures independently of the contrast of the stimulus figure as long as the stimuli could be seen clearly enough. This suggests that different mechanisms are involved in the visual persistence of motion-defined and luminance-defined figures. PMID- 1604864 TI - A new superbright LED stimulator: photodiode-feedback design for linearizing and stabilizing emitted light. AB - A new, reliable LED photic generator is described for analog stimulus presentation in vision research. A "superbright" red-emitting diode is controlled via optical feedback using a PIN-photodiode. A Maxwellian-view stimulator developed this way has been proven capable of covering intensities of retinal illuminance of over 26,000 td with a linear dynamic range of 3.7 log units. The device also has outstanding properties in linearity (distortion less than 0.12% at 100 Hz), frequency characteristics (d.c. to 2 kHz full-modulation bandwidth), stability (0.0002% fluctuation), and noise (S/N ratio greater than 76 dB). PMID- 1604865 TI - Simulation of neural contour mechanisms: from simple to end-stopped cells. AB - Early stages of visual form processing were modelled by simulating cortical simple, complex and end-stopped cells. The computation involves (1) convolution of the image with even and odd symmetrical orientation selective filters (S operators), (2) combination of even and odd filter outputs to a local energy measure (C-operator), (3) "differentiation" of the C-operator maps along the respective orientation (single and double end-stopped operators) and (4) determination of local maxima ("key-points") of the combined end-stopped operator activity. While S- and C-operators are optimised for the representation of 1-D features such as edges and lines, the end-stopped operator responses at the key points make explicit 2-D signal variations such as line ends, corners and segments of strong curvature. The theoretical need for this complementary representation is discussed. The model was tested on grey-valued images. PMID- 1604867 TI - A method to redefine stays on the 1985 National Nursing Home Survey. AB - This report describes a method for standardizing definitions of episodes of nursing home care in the 1985 National Nursing Home Survey. The method shows how the information on nursing home admissions and discharges collected on the Current and Discharged Resident Questionnaires can be used to redefine the endpoints of nursing home stays. The report also explains how errors caused by missing and inconsistent nursing home admission and discharge data were resolved. PMID- 1604866 TI - The information capacity of visual attention. AB - Is visual attention mediated by a general-purpose processor with a small data capacity? Such an attentive processor could perform a wide range of transformations upon a small amount of image data. We suggest that this limited capacity corresponds to a fixed amount of information, measured in bits. We measure how much information an observer's attention can handle by measuring how much we can restrict display information without impairing the observer's performance. The attentive visual tasks we study are the detection of a stationary dot in a field of moving dots, and the detection of a static square in a field of flashing squares. Performance of these tasks is perfect up to a critical number of elements (the span of attention) and then falls as the number of elements increases beyond this critical number. The display information required for unimpaired performance in each of these tasks is low; the results indicate that visual attention processes only 30 to 60 bits of display information. PMID- 1604868 TI - Diagnosing giant cell temporal arteritis. AB - Arteritis is a complex and totally underestimated clinical entity that may present in several ways. Due to the diversity of clinical features and the frequent overlapping of clinical syndromes, many different classifications are available for arteritides, but the simplest classification for the practicing physician is the broad division of arteritis into giant cell arteritis and non giant cell arteritis. Giant cell arteritis encompasses two distinct clinical entities that are pathologically indistinguishable from each other; but both involve arteritis of median and large-sized arteries characterized by an infiltration of giant cells. These include temporal arteritis and Takayasu's arteritis. The non-giant cell arteritis encompasses a greater variety of uncommon diseases that are often associated with other systemic processes such as systemic lupus erythematosus or periarteritis nodosa, and it generally results in ischemic organ dysfunction that is amenable only to medical treatment. Less commonly, however, non-giant cell arteritis may become manifested as acute arterial occlusion caused by circulating anticoagulants, abdominal apoplexy as intra abdominal bleeding from rupture of micro aneurysms of artery branches, gastrointestinal bleeding from local necrosis of the gastrointestinal tract, or deep-vein thrombosis secondary to hypercoagulable states. Although temporal arteritis has generated a voluminous body of literature, its precise etiology remains elusive. This study summarizes our experience in 15 cases of temporal arteritis and one case is presented to increase knowledge about this disease entity. PMID- 1604869 TI - A method for rapid intracompartmental pressure measurement. AB - A compartmental syndrome arises in situations where increased pressure within a limited space restricts the circulation by lowering the arteriovenous gradient and function of tissues within that space. Hypotension, hemorrhage, arterial occlusion, and limb elevation all appear to reduce the tolerance of limbs for increased tissue pressure. In early cases, patients with decreased levels of consciousness or when clinical evaluation is equivocal, pressure measurements become mandatory. Usually a single pressure measurement at the appropriate time will reveal the need for decompression, although in equivocal cases, a constant pressure measurement becomes necessary. The Wick catheter method has been widely used for this type of measurement, but we have developed a simpler system which is described in this article. PMID- 1604870 TI - Dr. Mills receives Family Doc Award. PMID- 1604871 TI - [Treatment freedom or arbitrary treatment? Critical thoughts on alternative healing methods]. AB - Complementary medicine is (by definition) scientifically untested. This does not mean that it is per se ineffective. Therapeutic success is generally due to more factors than specific therapy alone. Natural history of the disease and placebo effects always have to be taken into account. Therefore one can be misled and ineffective interventions can be followed by apparent success. The uncritical observer might mistakenly interpret this over and over again as apparent confirmation of an ineffective measure. The only solution is therefore to conduct a controlled trial. In the area of complementary therapy such trials are, however, of unsatisfactory quantity and quality. PMID- 1604872 TI - [A single daily dose with valproic acid. A pharmacodynamic and clinical study]. AB - A prospective clinical pharmacokinetic study was carried out in 10 adult patients with primary or secondary generalized tonic-clonic seizures on the efficacy of valproic acid (VPA) administered as a single daily dose in comparison with divided doses thrice daily. The observation period covered 28 weeks. Without changing the total daily dosage the once-daily treatment proved to be of at least equal clinical efficacy. The single daily dose was well tolerated without any increase in adverse effects. Following a once-daily evening dose the VPA plasma profiled displayed--as expected--a steep increase during the early evening hours, reaching a maximal value around 2 a.m.; afterwards the plasma levels decrease continuously until the next evening. By comparison, the thrice-daily regimen gave maximal VPA levels at 2 p.m. With respect to the pharmacokinetic parameters, the minimum VPA plasma concentrations proved to be significantly lower, and the fluctuations significantly higher during the once-daily administration period the mean maximum VPA plasma level was higher, but not significantly so. The bioavailability was not affected by the change in dosage regimen. Since once daily evening administration results in better patient compliance it seems appropriate to initiate VPA therapy with this simplified dosage regimen. For patients with inadequate seizure control on multiple daily doses of VPA it seems feasible--from a theoretical point of view--that the rate of attacks might be reduced after a changeover to a once-daily evening dosage regimen, but this has not yet been proven in clinical practice. PMID- 1604873 TI - [Critical illness polyneuropathy: clinical aspects and long-term outcome]. AB - Patients treated in intensive care units may develop a primary axonal form of polyneuropathy complicating sepsis and multiple organ failure more frequently than previously assumed. This critical illness polyneuropathy causes difficulty in weaning patients from the ventilator and delays further recovery and mobilisation. Over a period of two years we have treated five patients with flaccid tetra- or paraparesis. Recovery of motor function was largely satisfactory, but a long rehabilitation process was necessary. If attention were paid to detecting this disease in the early stages of intensive care neurorehabilitation might be facilitated. Hence, electrophysiological tests should be performed as soon as possible. The clinical outcome was markedly influenced by long-lasting neuropsychological disturbances in three of the five patients as well as by other complications such as joint contractures. PMID- 1604874 TI - Agenesis of the corpus callosum and epilepsy in two brothers. Neurophysiological and MRI features. AB - We report on two brothers with partial agenesis of the corpus callosum and seizure disorder presumably related to ectopic grey matter. Development of both patients was characterized by psychomotor retardation and focal epileptic seizures. Genetic examination revealed normal karyotypes. One brother showed a remarkable focal miniature spike and wave periodicity constantly observed on sequential EEG records. Magnetic resonance imaging revealed partial agenesis of the corpus callosum and ectopic grey matter. Prior computerized tomography failed to visualize ectopic grey matter and overestimated corpus callosum agenesis. The heterotopic grey matter, isolated from the surrounding inhibiting influences, is the most probable source of focal seizures and the partial connection of both hemispheres may explain secondary generalization of seizures. PMID- 1604875 TI - [Duplex ultrasound and color-coded Doppler ultrasound of visceral blood vessels in abdominal diseases]. AB - Duplex Doppler sonography (DS) and color-flow Doppler sonography (FDS) are noninvasive diagnostic methods for the evaluation of a patient with suspected vascular disease of the abdomen. They represent a useful adjunct to realtime sonography in the identification of normal and variant visceral vascular anatomy. Aneurysms and pseudo-aneurysms of visceral arteries are readily differentiated from other cystic lesions. DS and FDS have a high sensitivity in the detection of portal vein thrombosis and stenosis. Both methods allow the observation and measurement of splanchnic hemodynamics in patients with chronic liver disease and portal hypertension. Hence, DS and FDS already play an important role in the pre- and postoperative assessment of patients undergoing liver or pancreas transplantation. The possibility that DS and FDS may enable discrimination between hypovascular and hypervascular tumors is under clinical investigation. FDS facilitates an excellent anatomic display of the abdominal vasculature and allows easy placement of the Doppler sample volume. Consequently, quantitative data acquired with DS are accomplished within short scanning times. However, the diagnostic impact of both modalities depends to a great extent on the experience of the investigator. PMID- 1604876 TI - [Imaging procedures in diagnosis of laryngeal cancer with special reference to high resolution ultrasound]. AB - Sonography was compared with operative and histological results in 42 patients with advanced laryngeal cancer. Sonography was accurate in the imaging of supraglottic tumours. Infiltration of the base of the tongue (n = 4) and of the pre-epiglottic space (n = 12), as well as of the thyroid cartilage (n = 8) and subglottic extensions (n = 3) were visualized too. Infiltration of the piriform sinus was correctly assessed sonographically in 8 patients. Endoscopy was superior to sonography in endolaryngeal delineation of the tumour, with in exception of paraglottic tumours. In cervical lymph node staging sonography was more accurate than palpation (86% versus 69%). The diagnostic capabilities of sonography were compared with computed tomography and magnetic resonance imaging (MRI). Due to its widespread availability and high accuracy in the delineation of supraglottic and extralaryngeal extensions and in cervical lymph node staging, sonography can be performed as primary imaging modality in advanced laryngeal cancer. If it is not possible to obtain complete delineation of the tumour by sonography, MRI must be undertaken. PMID- 1604877 TI - [Neuroradiologic treatment possibilities of intervertebral disk displacement]. AB - A CT assisted method for automated percutaneous lumbar discectomy (APLD) is described. With this technique and introduction of a "pull and push" method as well extruded and sequestrated herniated lumbar discs as cervical herniated discs can be treated. The CT assisted discectomy was performed in 70 patients. The success rate was 86% in the lumbar region and 93% for cervical herniated discs. We believe that this percutaneous technique will increase the importance of interventional neuroradiology for this common disease. PMID- 1604878 TI - [Criteria for determining death in the Jewish religion]. AB - In accordance with Jewish thinking, life ends with the last breath. Analogous to the beginning of life, two leading principles are important for the bioethical assessment of the end of life: the sanctity of life and the fundamental importance of this world. Thus the criteria for the definition of death are the following, which have consequences for the questions of euthanasia, organ transplantation, autopsies and the status of the dead. PMID- 1604879 TI - [Medical use of fetal cells and tissue: ethical aspects]. AB - After considering the moral status of the living and of the dead human fetus, the article examines various ethical arguments connected with the use of fetal remains following elective abortion: financial or humanitarian incentives for the termination of pregnancy, conflicts of interest between mother and user, authority over fetal remains and modality of donation and utilization of the fetus. To prevent improper use of fetal remains it is recommended: to separate completely the decisions relating to abortion (first) and to the subsequent use of fetal tissues (second); to obtain explicit informed consent from the mother, making it impossible for her to direct any specific use of the fetal tissues; to base decisions on the method and timing of an abortion on the mother's health care needs alone; to exclude those involved in the process of abortion from any use of the fetus; to protect the anonymity of donor and recipient through an intermediary (tissue bank). PMID- 1604880 TI - [Glucose tolerance in the elderly--changes in insulin, C-peptide and glucagon secretion]. AB - The OGTT has been carried out by the authors with 25 older individuals (age 82 +/ 5.1) and 14 younger persons (age 28 +/- 9.0) who all showed neither clinical nor laboratory symptoms of apparent diabetes. During the test authors were determining venose glycaemia, insulin, C-peptide, glucagone and they computed some mathematical quantities enabling the estimation of the insulin secretion. The course of the OGTT of the older group showed higher values of glycaemia, insulin and C-peptide since the 60th minute tending to a duration or to a slow decline (up to the 120th minute). A significant difference in the glucagone values was found by the authors only in the case of fasting higher with the older ones (p = 0.01). The estimation of insulin secretion in the early phase of the OGTT was found by the authors significantly higher with the younger ones in both times. PMID- 1604881 TI - [Hypokalemia--incidence and severity in a general hospital]. AB - In a retrospective study the frequency of hypokalemia was investigated in a large group of hospitalized patients. In a period of 1 year 33,426 patients were hospitalized, of these 1,177 (3.52%) revealed serum potassium level of less than or equal to 3.0 mmol/l. On admission to the hospital 592 (50.3%) showed serum potassium levels within normal range and developed their hypokalemia in the hospital. A severe hypokalemia equal or lower 2.5 mmol/l was observed only in 0.54% of the patients. Hypokalemia was frequently associated with cardiovascular, gastrointestinal and urogenital diseases following by diabetes mellitus and polytraumas. The main causes of hypokalemia were diuretics and gastrointestinal potassium loss. Severe hypokalemia (less than or equal to 2.5 mmol/l) is a predisposing factor for the occurrence of ectopic ventricular activity in patients with preexisting myocardial lesions like left ventricular hypertrophy or after myocardial infarction. Therefore in patients with preexisting myocardial lesions and severe hypokalemia potassium replacement therapy may be needed. PMID- 1604882 TI - [Unconscious self control of diagnostic performance]. AB - Assessment of quality of general practitioners' performances and assessment of maintaining quality requires appropriate parameters. Such are the specific protocols developed by general practice basic research. They are guiding the doctor in more than 80 difficult first consultations. When assessing the quality of a colleagues performance, we cannot give him a good mark, if he does not utilize these new tools. His eventual contendedness with a mere consulting by experience and intuition does not count. If a general practitioner on the other hand conscientiously and broadly makes use of the protocols, we can attest him: As far as possible he is offering medical care with a minimal risk of overlook rare, hidden avoidably dangerous outcomes. That is a symptom of good general practice. PMID- 1604883 TI - [Disseminated encephalomyelitis--a mask for conversion neurosis?]. AB - A female patient, aged 24 years, with a case history of 9 years duration, 4 admissions to a neurological and 3 to a psychiatric ward was first diagnosed as multiple sclerosis. Diagnosis was based on neurological symptoms, whereas repeated laboratory values, electrophysiological measurements, CT and MRI scans were equivocal. Nevertheless this initial diagnosis profoundly influenced the further course of the illness: the patient ending up with an invalidity-pension. At that period she was admitted for her first psychiatric hospitalization after attempted suicide. Extensive investigations led to revision of the former diagnosis and Adlerian psychotherapy effected a remission of practically all neurological symptoms, so that the woman could be reintegrated socially and in her profession. Differential-diagnosis of multiple sclerosis is revised and the necessity of extensive, also psychodynamic, case-investigation is stressed, as is the need of consequent psychotherapy effected by a medical therapist. PMID- 1604884 TI - A comment on breast reconstruction. PMID- 1604886 TI - Acute adrenal insufficiency: hemodynamic and echocardiographic characteristics. AB - A patient with high output circulatory failure due to acute secondary adrenal insufficiency is described. The hemodynamic similarities and echocardiographic differences between volume expanded cortisol deficiency and septic shock are identified. PMID- 1604885 TI - Posterior hip dislocation in a rural emergency department. AB - Traumatic posterior dislocation of the hip is an infrequent but potentially severe injury. A commonly recognized cause of such injuries is motor vehicle accidents. There is increasing recognition, however, that this injury can be associated with other activities including several sports. Appropriate care requires recognition and prompt treatment to prevent long-term sequelae. A review of these experiences in a rural emergency department demonstrates additional causative agents and associated events as well as makes recommendations for care. PMID- 1604887 TI - OSHA blood-borne pathogens standard: an overview. PMID- 1604888 TI - Sample blood-borne pathogen exposure control plan. PMID- 1604889 TI - Tube feeding in Wisconsin: medicine and law in conflict. PMID- 1604890 TI - Ground-level ozone in Wisconsin: potential health effects. PMID- 1604891 TI - The great master of abdominal surgery: Nicholas Senn, MD, 1844-1908. PMID- 1604892 TI - [Glucocorticosteroid inhalation therapy of respiratory tract and lung diseases]. PMID- 1604893 TI - [Ambulatory rehabilitation of cardiovascular patients exemplified by acute myocardial infarction--an alternative?]. PMID- 1604894 TI - [Assessment of round-cell myocarditis and its therapy from a clinical and histologic-morphometric viewpoint]. PMID- 1604896 TI - [Human hemispherical specialization with special reference to neuroanatomical asymmetry]. PMID- 1604895 TI - [The value of continuous-wave Doppler ultrasonography in placental insufficiency]. PMID- 1604897 TI - [Historical overview of the development of health statistics until the first half of the 20th century--3]. PMID- 1604899 TI - [Report of the 2d Munich AIDS Days (27-29 Sept., 1991)]. PMID- 1604898 TI - [Jan Mikulicz in the light of Friedrich von Althoff's correspondence]. PMID- 1604900 TI - [Opportunistic infections in AIDS--diagnosis and therapy]. PMID- 1604901 TI - [Effectiveness and tolerance of nimodipine in long-term treatment of patients with organic brain disorders]. PMID- 1604902 TI - [Fournier gangrene]. PMID- 1604903 TI - [Cryptococcal meningoencephalitis following immunosuppressive therapy]. PMID- 1604904 TI - [Historical overview of the development of public health statistics up to the first half of the 20th century--2]. PMID- 1604905 TI - [A Lower Saxony Plague Treatise of the 18th century]. PMID- 1604906 TI - [Long-term tolerance of acarbose]. PMID- 1604907 TI - Intraindividual variability of anorectal manometry parameters. AB - The present study investigates the intraindividual day-to-day variability of anorectal manometry parameters. Manometric studies were performed in twelve healthy volunteers on three different days. A low compliance capillary perfusion system was used. The values measured on day 1 and day 2, as well as those on day 2 and day 3, showed no significant (p greater than 0.05) differences for any parameter in Wilcoxon's test. Mean percentage of differences as a measure for intraindividual day-to-day variation was relatively low for anal resting (mean: 13.5%) and maximal squeeze (17.5%) pressure. However, it was high for the threshold volumes for minimal perception (71.8%) and urgency to defecate (38.5%) during rectal balloon distention as well as for the minimal volume required to abolish recovery of the rectoanal inhibitory reflex (41.2%). We conclude that anal resting pressure and maximal squeeze pressure both are the most stable anorectal manometry parameters in man, at least over a period of a few days. PMID- 1604908 TI - Sodium fluoride-induced gastric mucosal lesions: comparison with sodium monofluorophosphate. AB - In a randomized double-blind study with two parallel groups of 10 male healthy volunteers each the response of gastric mucosa after a 7 days ingestion of sodium fluoride tablets (NaF) or sodium monofluorophosphate tablets (MFP) was compared. Gastroscopic evaluations were performed before treatment, day 1 and day 7. Simultaneously blood samples were collected for determination of laboratory data and serum fluoride values. In the MFP-group no severe gastric lesions were observed, whereas in the NaF-group in 7 of the 10 subjects significant gastric mucosal lesions including acute hemorrhages and free blood in the gastric lumen were found. The differences of the lesions scores in both groups were statistically significant (p = 0.0015). The serum fluoride content was comparable in both treatment groups. Possible adverse drug reactions were reported in 4 subjects with NaF and in 1 subject with MFP. In summary, under the experimental conditions used MFP is well tolerated by the stomach while NaF produces significant gastric mucosal lesions. PMID- 1604909 TI - [Diagnosis of alcohol-induced liver cirrhosis by indirect portal vein pressure measurement and liver venography]. AB - Indirect measurement of portal pressure and hepatic venography using the balloon catheter technique were investigated to assess the stage of chronic alcoholic liver disease, especially, to diagnose cirrhoses. 80 patients were studied and were categorised in 4 groups according to their liver histology: normal liver (N, n = 6), fibrosis (F, n = 27), incomplete cirrhosis (F/C, n = 11), complete cirrhosis (C, n = 36). Medians of wedged hepatic venous pressure gradient P (= WHVP-FHVP) and of a semiquantitative venographic score S showed increasingly higher values with more severe stages of the disease. Portal pressure (P) and venographic appearance (S) were correlated significantly (r = 0.778, p less than 0.0001). P was most useful to diagnose cirrhosis: Precirrhotic forms were associated with pressure gradients P less than or equal to 5 mm Hg in 97%. Incomplete cirrhoses were distributed in about 50% above and below P = 5 mm Hg, for complete cirrhoses P greater than or equal to 8 mm Hg was found in 97%. Pressure gradients P greater than or equal to 5 mm Hg indicated cirrhotic disease with a specificity of 97%. Sensitivity for complete cirrhoses was also high (97%), for incomplete cirrhoses however low (47%). Venography and measurement of portal pressure as diagnostic tools to predict cirrhoses of alcoholic origin were clearly more useful than biochemical tests (serum bilirubin, quick and cholinesterase). In comparison to laparoscopy the acceptance by patients is higher and the risk is lower if patients with known adverse reactions to contrast materials and risk of thyreotoxicosis induced by iodine are excluded. PMID- 1604910 TI - [Antibiotic-associated segmental hemorrhagic colitis: a case report]. AB - Pseudomembranous colitis is a well known complication of antibiotic therapy. Only recently few cases of another form of an antibiotic-associated colitis, the acute segmental haemorrhagic penicillin-associated colitis, have been described. We report another case and point out the importance of early colonoscopy to distinguish the disease from the pseudomembranous colitis. PMID- 1604911 TI - [Stomach wall abscess--endoscopic diagnosis and therapeutic possibilities]. AB - This is a case report of a rare gastric wall abscess of a 70 year-old woman who came to hospital with non-characteristic pain in the upper abdomen. The diagnosis was made by endoscopy. After endosonography the patient was treated by endoscopic drainage, antibiotics and abstinence of food. Two weeks later the abscess had healed. Subsequently recurrent arterial emboli occurred in the left leg leading to several operations. Two months after hospitalisation the woman died as a result of circulation failure induced by septicaemia. Surprisingly, post mortem examination showed endocarditis of the mitral valve with septical metastases in multiple organs. A review of the literature is given and etiology and pathogenesis of the gastric wall abscess are reviewed. The surgical treatment is compared with endoscopic therapy. PMID- 1604912 TI - [Extrinsic impression or submucous tumor? Contribution of endosonography to clinical assessment]. AB - Impressions of the lumen are frequently found during EGD. We examined 47 patients with 51 impressions by endoscopic ultrasonography and could clear their origin in 44 cases. We found 8 submucosal tumors, 1 submucosal cyst, 5 cysts and 2 malignancies of organs in the neighbourhood; in 28 cases the impression was caused by anatomical variations. In our opinion endoscopic ultrasonography is the method of choice in clearing the nature of impressions of the upper GI-tract. PMID- 1604914 TI - 34th annual meeting of the Hungarian Society of Gastroenterology and Hepatology. Balatonaliga, May 19-23, 1992. Abstracts. PMID- 1604915 TI - [Guidelines for endoscopic studies in primary sclerosing cholangitis]. PMID- 1604913 TI - [Is stomach cancer an infectious disease?]. PMID- 1604916 TI - [Biographical research methods in psychosomatic medicine, psychology and psychiatry]. AB - This review is centered around the current discussion regarding quantitative vs. qualitative research methodology in psychosomatic medicine, psychology, and psychiatry. In this context, the relevance of biographical methods is discussed. Furthermore, developmental aspects and the importance of biography and individual history in internal and psychosomatic medicine, psychiatry, psychology, and sociology are evaluated. Recent developments in biographical research methodologies such as biographical interviews and case control studies, longitudinal studies and biographical aspects of coping research, are presented as potentially valuable research tools. PMID- 1604917 TI - [Cognitive style of schizophrenic patients: ambiguity avoidance and decreased abstract thinking]. AB - The hypothesis of specific cognitive dynamics in schizophrenics is derived and tested in this study. This cognitive style should be characterized by a reduction of cognitive ambiguity and could be demonstrated in borderline patients in a previous study. This hypothesis is tested by applying Ertel's (1972) DOTA dictionary to responses of 25 acute and 25 chronic schizophrenics in the Holtzman Inkblot Technique. Furthermore the level of abstractness of the responses is investigated with the method of Gunther and Groeben (1978). According to the results both groups of schizophrenics had a significantly higher "Dogmatismus Quotient" (Ertel, 1972) than a sample of neurotics, but did not differ from borderline patients. Both acute and chronic schizophrenics used significantly less abstract nouns than borderline patients and neurotics. In contrast to borderline patients the reduction of cognitive ambiguity in schizophrenics is not connected with strong affects of anxiety and hostility. PMID- 1604918 TI - [Self-attention of psychosomatic patients]. AB - In the present study, based on the theory of objective self-attentiveness, a sample of psychosomatic patients was compared with persons in good health in a control group. It was established that psychosomatic patients had a significantly lower habitual tendency then healthy persons to reflect upon relevant, in particular emotional, self aspects; that they had a considerably higher habitual inclination to reflect upon social appraisals and the fulfilling of social standards; furthermore, they showed a distinctly higher social anxiety and lower self-acceptance. The findings have been discussed on the background of previous findings relating to alexithymia, and to enable the findings to be interpreted a model of a self stabilizing system was proposed. PMID- 1604919 TI - [An unusual syndrome of partial neurotic neglect]. AB - An impressive case of a 48-year-old woman is reported who after parental divorce when she was two-year-old grew up under a wicked stepmother and developed various obsessive symptoms. In context with some personal disappointments the woman increasingly neglected her home which after eight years appeared like a refuse pit. Simultaneously she continued to groom herself, to dress perfectly and to perform well in her office. She finally committed a suicide attempt when undelayable installations forced her to admit artisans into her apartment. Our case is discussed regarding the double aspect of obsession as a protective function as well as an obstacle for the individual in coping with life. PMID- 1604920 TI - [Configuration frequency analysis: Kieser's test against Victor's type and syndrome]. AB - Tests against types and anti-types as performed in Victor's Configural Frequency Analysis (CFA) have shown to be non-conservative. The conservative test by Kieser is introduced. It is applied to data describing a sample that performs below average in language tests. For data including small expected cell frequencies the Harms-Ihm adjustment is recommended. It leads to valid chi-squared testing even if expectancies are small. The problem of identifying more than two types or syndromes in exploratory CFA is discussed. PMID- 1604921 TI - [Training and social competence: single case analysis of behavior and cortisol]. AB - The aim of this study is to control the effectiveness of a training in social competence within the framework of a stationary therapy by means of observable behavior and to regard the course of salivary-serum- and urine cortisol in parallel with expected changes in behavior. The behavior assessment showed, that apart from anxiety and a deficiency in social competence, lack of trust and helplessness were essential variables (symptoms). Against the theoretical background of contemporary research in trust and helplessness it was tried to find relations between these factors and to show up relevance for therapy in the case in point. Guided by hypotheses the effects of training and therapy are verified by systematic observation of behavior as well as a significant change of the salivary cortisol values. The development of the therapy and the graphic similarity between the sequence of urine cortisol and the formalized Wortman Dintzer-Model suggest a corresponding interpretation reservedly. In parallel with Seligman's theories the process could refer to psychophysiological connections between helpless behavior and urine cortisol. PMID- 1604922 TI - [Clinical importance of silent ischemia]. AB - Objective signs of myocardial ischemia without angina pectoris or its equivalents define the syndrome of silent myocardial ischemia. Its significance lies in the prevalence and prognostic implications. As a prevalence, asymptomatic coronary heart disease can be found in 2.5% of men 40 to 60 years old. Silent myocardial ischemia is frequently found in patients with unstable coronary syndromes. The Framingham Study showed 25% of all myocardial infarctions as unrecognized by patients and physicians. The prognostic implications of silent myocardial ischemia are shown in large studies on prognosis of pathologic exercise-ECG's. Asymptomatic patients with pathologic exercise-ECG have always been recognized as having a significantly increased risk of myocardial infarction and death. Recently, many studies showed a worse prognosis for patients with asymptomatic transient ischemia on Holter-ECG. This can be found in patients with stable angina pectoris, unstable angina pectoris, patients with peripheral arterial disease, and patients after myocardial infarction. It becomes clear that prognosis is not defined by the pain, but by the severity of ischemia. Silent ischemia has to be viewed together with the severity of the underlying coronary heart disease. This synopsis will define the necessary steps for further diagnosis and treatment. PMID- 1604923 TI - [Is pre-hospital thrombolysis in acute myocardial infarct valuable as a routine measure?]. AB - In 4920 consecutive missions of the mobile intensive care unit Klinikum Steglitz, 1226 patients (25%) had chest pain of presumed cardiac origin. In 272 patients (22%) an acute myocardial infarction (AMI) was diagnosed in the field. In four patients the diagnosis was wrong; 11 patients with proven coronary artery disease had significant ST-segment elevation, but did not develop AMI. In hospital, a total of 406 patients had evidence of AMI; 173 of these (41%) were seen by an emergency physician in the field already within the first hour after onset of symptoms. In 6%, diagnostic ST-elevation was not recognized by the emergency physician; 27% had non-diagnostic ECG changes (11% bundle-branch block). Prehospital thrombolysis within 4 h after symptom onset was performed in 126 of 205 patients (61%); 74 of these patients were seen by the emergency physician within the first hour. The main reason for exclusion was advanced age. Inclusion of older patients and also those with bundle-branch block could further increase the prehospital thrombolysis rate. CONCLUSION: With an effective emergency medical system a large proportion of all patients with AMI can correctly be identified and properly treated with a thrombolytic drug in the field. The time gain is considerable. PMID- 1604924 TI - [Detection of dissection of the thoracic aorta: improved specificity by magnetic resonance tomography in comparison with echocardiography techniques]. AB - The purpose of this study was to assess the reliability of conventional transthoracic and transoesophageal two-dimensional echocardiography combined with color-coded Doppler flow imaging (TEE) and ECG-triggered magnetic resonance imaging (MRI) for the diagnosis of thoracic aortic dissection and associated epiphenomena. A total of 53 patients with clinically suspected aortic dissection were subjected to a transthoracic and transoesophageal ultrasound examination and magnetic resonance imaging; the results of each imaging modality were compared and validated against the morphological standards of contrast angiography (n = 53) and/or intraoperative findings (n = 27) or autopsy (n = 7). In this series no deleterious events were encountered with either non-invasive imaging method. In contrast to conventional echocardiography the sensitivities of both MRI and TEE were 100% for detecting a dissection of the thoracic aorta, irrespective of its location. However, the specificity of TEE was lower than the specificity of MRI for a dissection (TEE 68.2% versus MRI 100%; p less than 0.005), which resulted from false positive TEE findings mainly confined to the ascending segment of the aorta (specificity of TEE 78.8% versus 100% by MRI; p less than 0.01). In addition, MRI proved to be more sensitive than TEE in detecting the formation of thrombus in the false lumen of both the aortic arch (p less than 0.01) and the descending segment of the aorta (p less than 0.05). There were no discrepancies between the two imaging techniques in detecting the site of entry to a dissection, aortic regurgitation or pericardial effusion. Both MRI and TEE are atraumatic, safe, and highly sensitive methods to identify and classify acute and subacute dissections of the entire thoracic aorta. However, TEE is associated with lower specificity for lesions in the ascending aorta. These results may still favor TEE after a precursory screening transthoracic echogram in suspected aortic dissection, but will establish MRI as an excellent method to avoid false positive findings. Anatomical mapping by MRI may emerge as a promising comprehensive approach and, eventually, as a morphological standard to guide surgical interventions. PMID- 1604925 TI - [Assessment with magnetic resonance tomography of anatomy and ventricular function after Mustard correction of transposition of the great arteries]. AB - In order to evaluate postoperative sequelae and ventricular function after Mustard-operation in patients with transposition of the great arteries (TGA), 30 patients were assessed by magnetic resonance imaging in EKG-triggered spin-echo (SE) and gradient-echo (GE) technique. Twenty-three patients, aged 4.7 to 15.8 years, had transposition of the great arteries with intact ventricular septum with or without left-ventricular outflow tract obstruction (TGA+IVS +/- SPS). Seven patients aged 9.5 to 21.7 years had transposition of the great arteries with ventricular septal defect (TGA+VSD). Five patients showed a residual baffle leak, one had a pulmonary venous obstruction, five an obstruction at the caval veins, 13 a left-ventricular outflow tract obstruction, and 14 a tricuspid regurgitation. Right-ventricular enddiastolic volume in patients with TGA+VSD (77.0 +/- 25.5 ml/m2) was significantly higher than in patients with TGA+IVS +/- SPS (61.2 +/- 12.0 ml/m2). In TGA+VSD right-ventricular ejection fraction (47.6 +/- 13.0%) was significantly lower than in patients with TGA+IVS +/- SPS (56.7 +/ 10.7%). The ratio of muscle masses of right to left ventricle was 1.8:1 in patients with TGA+IVS +/- SPS and 2.5:1 in patients with TGA+VSD. In conclusion, after Mustard-operation in patients with transposition of the great arteries (TGA) magnetic resonance imaging provides a comprehensive and noninvasive assessment of postoperative sequelae, residuae, and ventricular function and will, therefore, become the method of choice for postoperative evaluation. PMID- 1604926 TI - [Perforation of a temporary transvenous pacemaker electrode in the left hemithorax. Diagnostic value of echocardiography]. AB - We report a rare malposition of a temporary transvenous pacemaker electrode. A pacemaker electrode was inserted in a patient with acute postero-lateral infarction. The correct position of the electrode tip was controlled by fluoroscopy. Capture and sensing functions worked regularly. Four days later, angina-pectoris-like complaints occurred again. Chest x-ray film revealed the tip of the electrode in the left hemithorax. Echocardiographic assessment showed a penetration through the interventricular septum into the left ventricle. The electrode passed the left ventricle, penetrated the anterior-lateral free wall and reached the left pleural space. A thoracotomy was performed immediately. The electrode was retracted under visual control. A spurting arterial bleeding from the left ventricle was secured with a purse-string ligature. This case report emphasizes the value of echocardiography in the evaluation of a malposition of a transvenous pacemaker electrode. PMID- 1604928 TI - [Abstracts from the 58th annual meeting of the German Society for Cardiac and Circulatory Research. Mannheim, 23-26 April 1992]. PMID- 1604927 TI - [Superior vena cava syndrome after pacemaker implantation. Increased risk with DDD-systems? Case report]. AB - Superior vena cava syndrome due to transvenous pacing leads is a rare event. Local infection as well as multiple leads are important predisposing factors. The case of a patient with superior caval syndrome after multiple complicated permanent pacemaker insertions is presented. Medical treatment was unsuccessful. At operation a fibrous narrowing of the vena cava superior was found. The two leads (DDD-pacemaker) were left in place. A Goretex patch was used for enlargement of the anterior wall of the vein. Postoperatively, the patient remained free of symptoms and the vein was patent angiographically. In case of failure of medical management surgical correction should be attempted without delay. PMID- 1604929 TI - Nucleotide sequence analysis of the HA1 coding portion of the haemagglutinin gene of swine H1N1 influenza viruses. AB - The nucleotide and deduced amino acid sequences coding for the HA1 portion of the haemagglutinin (HA) genes of three swine influenza viruses were determined and compared with published HA sequence data for human H1N1 influenza viruses. Sequence differences between the classic swine influenza HAs sw37 (A/swine/29/37) and NJ76 (A/New Jersey/11/76) were randomly distributed in the molecule without being confined to antigenic sites. In contrast, sequence differences between the HAs of sw37 and the antigenically atypical strains sw38 (A/swine/Northern Ireland/38) and sw39 (A/swine/Cambridge/39) were clustered in hypervariable regions, similar to the pattern of changes that was present between sw37 and the human strains PR834 (A/PR/8/34) and WSN33 (A/WSN/33). Sequence homologies of the European swine influenza strains (sw38, sw39) were higher with the HAs of the human strains (PR834, WSN33) than with the classic swine influenza HAs (sw37, NJ76). Phylogenetic analysis showed that the HA genes of these two European swine influenza strains emerged from a different evolutionary lineage of H1 HAs than the HAs of classic swine influenza strains. PMID- 1604930 TI - The nucleotide and deduced amino acid sequence of the M gene of phocid distemper virus (PDV). The most conserved protein of morbilliviruses shows a uniquely close relationship between PDV and canine distemper virus. AB - The nucleotide sequence of the matrix gene (M) of a recently identified morbillivirus, phocid distemper virus (PDV), was determined and the amino acid composition deduced. The M gene of PDV shared many characteristics with the corresponding gene in other morbilliviruses. The nucleotide homology with the closely related canine distemper virus (CDV) was maximum at 67% followed by measles virus (MV) (58%) and rinderpest virus (RPV) (56%). The length of the 5' long untranslated region of PDV (408) was similar to that of CDV (406) but was somewhat shorter than that of MV (425) and RPV (437). The deduced matrix protein of PDV showed structural characteristics similar to the corresponding proteins of other morbilliviruses. PDV and CDV M proteins showed a remarkably high amino acid homology of 90%. The percent amino acid homology among other morbilliviruses was between 73-77%. The M protein was the most highly conserved protein among all morbilliviruses viral components. PMID- 1604931 TI - Cell culture propagation modifies the African swine fever virus replication phenotype in macrophages and generates viral subpopulations differing in protein p54. AB - We have detected 86 African swine fever (ASF) virus-induced proteins in infected pig macrophages by two-dimensional electrophoresis. No differences among protein patterns of wild-type viruses could be observed by this methodology. However, during cell culture adaptation and propagation we have characterized changes in the molecular weight of the ASF virus specified protein p54, which show direct correlation with both size and number of viral subpopulation variants generated during cell culture propagation. Passages in culture appear to select for viral subpopulations that specify p54 proteins with higher molecular weights than the wild-type virus. The virus propagation in cell culture also affected its replication phenotype in pig macrophages decreasing the viral titers in these cells between passage 44 and 81. Nevertheless, the changes observed in p54 did not imply differences in biological properties, such as infectivity, virulence or host cell range among viral clones isolated, each one specifying for only one p54 form with different molecular weight. This protein becomes then a valuable quantification marker to follow evolution and generation of ASF virus diversity in vitro. PMID- 1604932 TI - Lactate dehydrogenase-elevating virus (LDV): subgenomic mRNAs, mRNA leader and comparison of 3'-terminal sequences of two LDV isolates. AB - The 3'-terminal 1314 nucleotides of the genome of one isolate of lactate dehydrogenase-elevating virus, LDV-P, has been derived by sequence analyses of cDNAs from several genomic libraries and compared to that of another LDV isolate, LDV-C (Godeny et al. (1990) Virol. 177, 768-771). The 3'-non-coding segment of 80 nucleotides of the two LDV genomes is identical, whereas marked, but varying nucleotide and amino acid divergence is apparent in the three upstream overlapping open reading frames (ORF). The third ORF from the 3'-end exhibits only 82% nucleotide and 90% amino acid identity, whereas the 3'-terminal ORF, which encodes the nucleocapsid protein, exhibits approximately 99% amino acid identity. The second 3'-terminal ORF encodes an 18.8 kDa protein which lacks N glycosylation sites but possesses 2 or 3 potential transmembrane helices in the N terminal half of the molecule. A similar membrane organization is observed for the corresponding protein of equine arteritis virus and the M protein of mouse hepatitis virus. The sequence analyses combined with Northern hybridization analyses of RNA from LDV-infected macrophages and spleens of LDV-infected mice indicate that the three ORFs encoded by the 3'-terminal end of the LDV genome are expressed via the three smallest mRNAs (mRNAs 6-8) of the seven subgenomic mRNAs of LDV (mRNAs 2-8), which range in size from about 0.8 to 3.6 kb. All mRNAs have been shown to carry poly(A)-tracts and a common leader sequence. The seven mRNAs were produced in infected macrophage cultures concomitantly with genomic LDV RNA. Maximum LDV RNA synthesis was observed between 6 and 8 h post-infection. The same seven subgenomic mRNAs were detected in macrophages infected with three different isolates of LDV, but different relative amounts of some of the mRNAs were produced. The relative proportions of molecules of mRNAs 1-8 present in 6 h LDV-P infected macrophages were about 13, 5, 5, 8, 6, 11, 11 and 27% of the total, respectively. PMID- 1604933 TI - Nucleotide sequence of the 3'-terminal region of potato virus A RNA. AB - The sequence of the 3'-terminal region of the genome of the potato virus A (PVA) was obtained from two independent cDNA clones. This sequence is 1383 nucleotides long and contains an open reading frame of 1178 nucleotides, ending with the translation termination codon TAA and followed by untranslated region of 205 nucleotides. Since the N-terminal amino acid of the coat protein of PVA was blocked, the position of the putative coat protein cleavage site has been deduced by searching for consensus sequences and by the analogy to other potyviruses. The resulting coat protein is 269 amino acids long and has a calculated MW of 30257. Two independently sequenced cDNA clones show sequence heterogeneity at four nucleotide positions: C422/A422, G432/A432, G446/A446 and T706/C706. Three first nucleotide differences are located at the PVA coat protein N-terminal region and led to the change of the amino acid. The coat protein of PVA displayed significant (73-78%) sequence homology to the coat proteins of six other potyviruses: papaya ringspot virus (PRV), pepper mottle virus (PeMV), plum pox virus (PPV), potato virus Y (PVY), sugarcane mosaic virus (SCMV) and tobacco vein mottling virus (TVMV). Even higher sequence homology (82%) was detected with a coat protein of a seventh potyvirus, tobacco etch virus (TEV). Major differences among the coat protein of PVA and of other potyviruses are located at the N terminal region of the coat protein. PMID- 1604934 TI - Epidemiology and environmental risks. PMID- 1604935 TI - Epidemiology and Health for All. The role of epidemiology in a health policy. AB - World Health Organization's goal Health for All is the starting point for a most ambitious health policy ever. The paper analyzes the role of epidemiology in the Organization's work, particularly in the Health for All development. During WHO's early years, epidemiology helped to design and carry out major public health campaigns against such scourges of the humanity as yaws, tuberculosis, malaria and small pox. When the Organization during the 1960s began to emphasize the need to develop the infrastructure of health care, health services research partly replaced epidemiology as WHO's main scientific allay. After the Health for All policy was launched in 1987, epidemiology has again played a major role in establishing the scientific background of the policy. The European experiences show how the epidemiologists can help WHO to identify the most important health problems and set achievable and measurable targets for them. The paper concludes that epidemiology serves to identify problems, show ways to solve them, monitor the changes in the situation and evaluate the achievements. PMID- 1604936 TI - [Epidemiology of risks in the workplace]. AB - Epidemiologic studies of occupationally exposed subjects allow to detect diseases caused by the work environment and to identify hazardous exposures. They provide the basis for preventive measures and workers compensation. Occupational epidemiology traditionally emphasized the study of work related cancer. Long latency periods for the development of most cancers and limited information about the exposure history of the study subjects are problems for all study types. The specific advantages and limitations of different study designs are discussed. Research strategies in occupational epidemiology are demonstrated using as an example two studies from the American tire and rubber industry. The specific contributions of a historical cohort study and a nested case-control study, concerning the association between lymphosarcoma and exposure to solvents, are discussed. Experiences and first results from a historical cohort study in the German rubber industry are reported. Future research in occupational epidemiology should concentrate more on the study of work related morbidity such as musculoskeletal disorders, hearing loss, accidents and the influence of the work environment on the mental and physical well being. Modern research methods such as prospective cohort studies or workforce monitoring should be used more often. Prospective cohort studies provide quantitatively and qualitatively more precise information about exposures and potential confounders, e.g. cigarette smoking or alcohol consumption, than traditional study methods. The promising perspectives of biological markers warrant further research. The situation of occupational epidemiology in Germany can only be improved if all concerned parties and institutions realize the importance of occupational epidemiology. Laws concerning data confidentiality which seriously hamper epidemiologic research must be modified. PMID- 1604937 TI - [Epidemiology and prevention of AIDS]. AB - For ten years now the Aids epidemic has worried mankind. In the same time the virus has spread all over the world. Ever more people fall ill. 56,000 cases of Aids have been notified only in Europe until June 1991. Prognoses for the future are difficult to make, some areas will be strongly affected. The surveillance and epidemiology for HIV and Aids are to be expanded with reasonable means. Such knowledge will serve as basis for prevention, which in some areas and with certain groups has already shown a certain effectiveness in the last years. In Switzerland e.g., use of condoms in the age group of 17-30 with casual sexual contacts has increased from 7% (1986) to about 50% (1991). The number of sexually transmitted diseases has decreased. Solidarity is the basis for effective prevention programmes concerning Aids. Maturity of people concerning health has to be stimulated by means of information and education. PMID- 1604938 TI - Trends of HIV infections using the anonymous mandatory reporting system and other data sources in Switzerland and in the Federal Republic of Germany. AB - In Switzerland and in the Federal Republic of Germany the reporting of HIV infections is based on an anonymous mandatory reporting system for laboratories. In Switzerland, physicians have to complete a questionnaire on the patient's clinical status and risk behaviour. To make a rough estimate of the prevalence of HIV infections in the general population at low risk, data on blood donations are used in both countries. In Switzerland, additional data with information on positive and negative test results have been obtained since 1985 from anonymous test sites. In both countries, the data do not show evidence of an increasing incidence of HIV infection. The number of positive test results reported by the laboratories and physicians remains stable, and the rates of HIV-positive blood donations are declining. In the Federal Republic of Germany, homo-/bisexual men play the most important role in the epidemic, whilst in Switzerland, injecting drug users contribute most to the burden of HIV infection, and the proportion of persons probably heterosexually infected is increasing steadily. Possible selection biases need to be further discussed. PMID- 1604939 TI - Predictors of high risk sexual behaviour in gay and bisexual men. AB - Evidence of high risk sex between gay men continues to be reported, as does a range of sexual behaviour. Three hundred and sixty-nine homosexually active men from different areas of England were each assessed twice at an an interval of 9 months in order to examine the extent to which a number of social-psychological factors predicted subsequent high risk sexual behaviour. Few of the variables were significantly related to unprotected receptive anal sex in the way that the Health Belief Model predicted, except for some perceptions of costs and benefits of safer sex. However, whether or not men were involved in a regular relationship with a partner was strongly associated with high risk behaviour. The implications of these results are that health education interventions should focus on alerting all men to the social context in which high risk sex is more likely to happen: the regular partnership. PMID- 1604940 TI - [Changes in occupational status following cancer. An empirical study on occupational rehabilitation]. AB - The importance of vocational integration has increased during the last years, whereas an analysis of the literature shows, that research in this field has been neglected especially in german speaking countries. This study investigates the situation and the problems of vocational integration after cancer. 380 former patients with different diagnoses treated in a university medical center have been asked by a self developed questionnaire for their experiences in treatment and medical rehabilitation, their actual impairment in physical and vocational functioning, their estimation of rehabilitation success, their actual employment problems and the changes of job conditions due to cancer. As the results show, more than one third of the sample returned to work often reducing working time or changing their job. Especially older patients with worse prognoses have been retired early. Special programs of vocational rehabilitation are not used by patients we examined, whereas programs of medical rehabilitation are used showing great differences between diagnostic groups. The return to work is influenced by age, tumor localisation, prognosis and the former status in job. The results are discussed with regard to the problems of psychosocial rehabilitation of cancer patients. PMID- 1604941 TI - [Mentally ill patients: viewed from 2 perspectives. A methodological contribution on attitudinal research in psychiatry]. AB - The impact of the change in perspective (i.e. the personal opinion of those questioned versus what they perceive the others' opinion toward the mentally ill to be) on the results of the questionnaire is examined based on data from two population surveys measuring attitudes towards the mentally ill. As expected, the respondents' attitudes towards the mentally ill are more positive if they are asked to give their own opinion. The impact that the variation of the two formulations of these questions has on the respondents increases with their level of education and reaches a substantial amount among those with "Abitur". Furthermore, the answers are clearer and more definite if those questioned are asked for their personal opinion. PMID- 1604942 TI - [Subjective, objective and mammographic late results following reduction mammoplasty]. AB - Between 1969-1989 340 mammaplasty operations were performed in 172 patients. The mean weight of resected breast tissue was 704 +/- 418 g for one breast. In 18.2% more than 1000 g were resected. 1990 the patients were reexamined. Physical complains could be eliminated in nearly all mammaplasty patients. The cosmetic result at the time of evaluation was good or very good in 82% if judged by the patients and in 70% if judged by the surgeon. The assessment of the clinical examination was normal in 89% and in the mammographic examination in 80%. PMID- 1604943 TI - [Late results of breast augmentation]. AB - Late results of augmentation mammaplasty with dermis fat transplants and implants are presented and discussed separately. With correct handling and strict indication a mammary implant heals in without complications and with good results. The problem of capsular fibrosis is discussed. Prerequisites for augmentation mammoplasty are detailed information about and strict selection of candidates. PMID- 1604944 TI - [Secondary lymphedema of the arm following primary therapy of breast carcinoma]. AB - 1107 cases of lymphedema of the ipsilateral arm (27%) were found in 4011 female breast cancer patients suffered from 4101 breast cancer, seen in the Bad Trissl hospital between 1972 and 1990. The right arm was affected in 47.5%, the left in 52.5%. Primary treatment had consisted of operation alone in 1630 patients with a consecutive rate of edema of 20.3%. Additional irradiation increased this rate up to 31.4% (n = 2471). The rate of edema after radical mastectomy (n = 731), modified radical mastectomy (n = 3149) and breast preserving operation (n = 221) were 39.2% and 9.5% respectively. Adjuvant radiotherapy increased the edema rate of each the surgical procedures (radical mastectomy alone 22.7%, with irradiation 44.7%, modified radical mastectomy alone 19.9%, with irradiation 29.3%, breast preserving operation alone 6.9%, with irradiation 10.4%). During the observation time from 1972 to 1990, the edema rate was reduced from 38% to 18%, reflecting the change of the chosen therapy modalities (radical surgery and conventional irradiation from the 50th's to the early 70th's, breast preserving techniques with modern megavoltage irradiation in the late 80th's). A further reduction of the lymphedema rates by minimization of the aggressiveness of the treatment seems to be possible and should be taken into account for preserving an optimal quality of life. PMID- 1604945 TI - [Assessment of prognosis in breast carcinoma by lay persons and by physicians]. AB - Between 1986 and 1988 five hundred women with suspicion of breast cancer were asked for private prognosis. 29% did not answer. In the end 43.2% had a breast cancer. 47 of the patients had worked in Public Health. 54.4% of all had seen the possibility of cure chance in more than 50%, but only 39.4% with a medical job respectively 0% of patients with a diploma of a medical university have seen this chance. PMID- 1604946 TI - [Surgical heritage. The 200th birthday of Johann Friedrich Dieffenbach]. PMID- 1604947 TI - [How can the Commission of Approval influence the quality of education?]. PMID- 1604948 TI - [Role of the Commission of Approval in the education of specialist candidates in general surgery]. PMID- 1604949 TI - [Education general surgery: viewpoint of the candidate surgeon]. AB - An opinion poll about the surgical training performed among the Flemish surgeons in training showed us rather critical results. 54 of 62 assistants consider the technical training capable of improvement, 48 of 62 surgeons in training believe their is a lack of possibilities for a sound theoretical education. To improve the present day needs the following changes are suggested: the reduction of the number of training centers, the raise of the operative (and supervised) activities and more possibilities for a good theoretical education, changes more achievable in case of reduction of the overload with nonoperative tasks. The surgeons in training should have their say in the reorganisation of the training in surgery. PMID- 1604950 TI - Foreign education and scientific research: a Canadian experience. PMID- 1604951 TI - [Educational model anesthesia]. PMID- 1604952 TI - [Creation and functions of the "Collegium Chirurgicum Plasticum"]. PMID- 1604953 TI - [Education in surgery--the Consilium Chirurgicum Belgicum]. PMID- 1604954 TI - [U.E.M.S. and the coordination of the education in Europe (Union of European Medical Specialists)]. PMID- 1604955 TI - [Short-term perspective of education]. PMID- 1604956 TI - The components of energy expenditure in human obesity. PMID- 1604957 TI - Pathophysiology and treatment of the obesity-related arterial hypertension. AB - While obesity is frequently associated with arterial hypertension, the underlying mechanism is still poorly understood. A marked drop in blood pressure in response to hypocaloric carbohydrate-poor diet, occurring usually in obese hypertensive patients even before any significant reduction of body weight is achieved, strongly suggests that the obesity related metabolic abnormalities rather than the degree of fatness as such, are involved in the association between obesity and overweight. Among several possible mechanisms, the state of insulin resistance with hyperinsulinaemia, as well as increased activity of the sympathetic nervous system, are probably responsible for the development of arterial hypertension in obese subjects. The arterial hypertension may be promoted by these two mechanisms, which are probably causally related, closing the pathophysiologic loop leading to hypertension. Both mechanisms may promote the development of haemodynamic abnormalities which characterize the hypertension associated with obesity, i.e. the renal sodium and fluid retention with ensuing expansion of the extracellular volume and the increased peripheral vascular resistance. PMID- 1604958 TI - Abnormalities of lipid metabolism in overweight subjects. PMID- 1604959 TI - From obesity to type 2 diabetes. AB - Obesity is a well-known risk factor for the development of non-insulin-dependent diabetes mellitus (NIDDM). Both insulin resistance and concomitant B-cell dysfunction are necessary for the development of NIDDM. Insulin resistance, probably genetically determined but worsened by obesity, appears to be the primary defect that leads to impaired glucose tolerance. However, B-cell dysfunction plays a critical role during progressive deterioration from mild impaired glucose tolerance to severe NIDDM. PMID- 1604960 TI - Endocrine abnormalities related to total and regional fat mass accumulation. PMID- 1604961 TI - Serotoninergic system: therapeutic implications in obesity. PMID- 1604962 TI - Angiographically occult brainstem vascular malformation: a longitudinal comparison of magnetic resonance imaging (MRI) and multimodal evoked potential (EP) recordings. AB - Over a period of several years, a patient with angiographically occult vascular malformation (AOVM) involving the brainstem was longitudinally studied by means of serial Magnetic Resonance Imaging (MRI) and multimodal Evoked Potential (EP) recordings (visual-VEP, brainstem auditory-BAEP, somatosensory--SEP--by stimulating median and peroneal nerves). MRI did contribute to an accurate definition of AOVM features. In particular, it was able to follow over time the AOVM size, and to discriminate between recent and old bleedings. Multimodal EP recordings displayed different pathological BAEP and peroneal SEP values, which documented a transient segmental brainstem involvement (related to the presence of hemorrhage), along with persistent and probably irreversible signs of diffuse brainstem dysfunction. Thus, MRI and EP assessment is useful in monitoring the clinical course of brainstem occult vascular malformations. PMID- 1604963 TI - Cerebral hemorrhage and thrombotic thrombocytopenic purpura during ticlopidine treatment: case report. AB - We report the second case of thrombotic thrombocytopenic purpura occurring during ticlopidine therapy. A cerebral hemorrhage was the first sign of the thrombocytopenia. Even if thrombocytopenia is a rare occurrence with ticlopidine therapy, we stress that platelets must be repeatedly monitored. PMID- 1604964 TI - Comprehensive medical examination of a group of patients with alleged adverse effects from dental amalgams. AB - Mercury from dental amalgams does not seem to cause dose-related intoxications. However, animal studies have shown that high-dose exposure to mercury may support various types of immunologic reactions. Ten patients claiming that their symptoms were caused and aggravated by amalgam therapy were selected for a study of the effects of removal of one amalgam restoration followed by placing of a composite filling. Clinical symptoms and the result of laboratory tests were recorded. Six patients had contact allergies to metals, three of them to mercury ammonium chloride. The comparison of pre- and post-experimental test results showed significant reductions in p-IgE and dU-albumin and significant increases in p-C3d and dU-beta 2-microglobulin. There was no laboratory evidence of a direct toxic effect by mercury on the patients. The observed response by some of the studied factors to the low acute exposure to amalgam may imply that an activation of the immune system occurred. PMID- 1604965 TI - Glycosaminoglycans in normal and osteoarthrotic human temporomandibular joint disks. AB - Glycosaminoglycans in normal and osteoarthrotic temporomandibular joint disks were studied by means of high-performance liquid chromatography methods. Normal disk tissue contains galactosaminoglycans (chondroitin sulfate and dermatan sulfate) as the main polysaccharides and with smaller amounts of hyaluronate and heparan sulfate. The galactosaminoglycans are mainly sulfated in 6-position, and some of the disaccharides contain iduronic acid. There was a slight general variation in glycosaminoglycan concentration with increasing age. In the severely arthrotic disks the content of glycosaminoglycans was considerably lower than in normal disk tissue. This decrease was far more extensive than that observed in relation to age in normal tissue. The 4/6-sulfate ratio of the galactosaminoglycans was increased, whereas the proportion of iduronic acid was markedly decreased. PMID- 1604966 TI - Visual and profilometric wear measurements. AB - Wear of composites can be estimated by the degree of marginal discrepancy between the prepared cavity wall and the occlusal margins of composites. Such evaluations are done on casts by comparing and rating the marginal discrepancy with those on standard casts. We analyzed the reliability of this technique on metal and stone specimens. These specimens contained grooves of different width and depth. For the visual comparison we used stone casts of machined standards of known groove depth. We measured the depths of the metal specimens with a profilometer and made stone casts of these original specimens. Using the stone casts of the standards, five dentists estimated the unknown groove depths on the remaining stone casts. These estimates were done under standardized conditions and repeated by each dentist on five different occasions. The results showed that visual depth evaluations of die stone specimens underestimated the depths when compared with the values measured with a profilometer on the original metal models. One investigator gave significantly different (p less than 0.05) groove depth estimates at different occasions. PMID- 1604967 TI - Palatine and mandibular tori. A morphologic study in the current Norwegian population. AB - Five thousand Norwegians, 2783 females and 2217 males, ranging in age from 16 to 89 years, have been screened for the presence of torus palatinus and/or torus mandibularis and analyzed with regard to size and shape of tori, sex, and age. The tori have been classified according to size as small, medium, and large. No measurements have been made, consistent with the view that these characteristics are non-metrical and should be assessed by means of a standard procedure. The prevalence figures of both tori were fairly low, in accordance with former reports. In torus palatinus there was female predominance, with a sex ratio of 5:3. In torus mandibularis the males were in majority, and the sex proportion was 4:3. In both sexes prevalence of the two tori was highest in the 35- to 65-year age group. Further analysis indicated in both tori a real correlation between prevalence and size and some correlation also between size and shape of torus palatinus but not of torus mandibularis. The figures of concurrence of the two tori were low, denoting a non-significant correlation. Still, the analysis showed that each torus occurred more than twice as frequently in an individual bearing the other torus. Torus morphoanalysis, explaining diverging patterns of clinical conduct in the two tori, and the relative weight of hereditary versus environmental factors as morphogenetic determinants of the condition, including a quasi-continuous genetic or threshold model, have contributed to shed new light on the torus phenomenon. The occurrence and propagation of torus mandibularis complies reasonably well with this model, and the present analysis indicates that even torus palatinus should appropriately be considered a threshold character. PMID- 1604968 TI - Copper in approximal plaque from conventional and non-gamma-2 amalgam restorations. AB - Differences in copper concentrations found in plaque adjacent to conventional compared with copper-rich non-gamma-2 amalgam fillings were evaluated. Plaque was sampled at baseline and up to 2 months after polishing of two to four fillings of each type of amalgam in six patients. Copper concentrations of several hundred ppm were found, with higher values in plaque sampled from copper-rich amalgam. However, the copper release from the copper-rich amalgam probably has very little influence on plaque ecology owing to a relatively low copper ion activity because of stable copper complexes in plaque. PMID- 1604969 TI - Metal release from arch bars used in maxillofacial surgery. An in vitro study. AB - Surgical arch bars (splints) are used in maxillofacial surgery as an aid to intermaxillary fixation procedures. Two different types of stainless steel arch bars, a solid bar and a silver-brazed bar, were studied with regard to metal release in vitro. Arch bars were ligated to jaw models and immersed in 0.9% saline solution. The electrolyte was analyzed for Ni, Cr, Fe, Cu, Zn, and Cd by atomic absorption spectrophotometry on days 3, 10, and 28. The amounts of metal released from the brazed arch bar were 140-600 times higher than those released from the solid arch bar. Clinical implications are suggested. PMID- 1604971 TI - Collegium Oto-Rhino-Laryngologicum. York, September 1-4, 1991. PMID- 1604970 TI - Macroscopic and microscopic findings of areas with radiologic erosions in human temporomandibular joints. AB - The aim was to describe the macroscopic and microscopic findings of areas with radiologic erosions in the human temporomandibular joint. An autopsy material of 40 human joints, removed as blocks, was examined with tomography, and an erosion was found in 37 areas. A macroscopic and a microscopic examination focused on the presence of the calcified cartilage zone (CCZ) was performed in these areas. In the condyle 13 of 14 areas with a radiologic erosion showed denudation of bone macroscopically. Microscopically, these areas were covered by a thin fibrocellular tissue, and the CCZ was absent. In the temporal component, only 1 of the 23 areas showed bone exposure macroscopically. Microscopically, the soft tissue in these areas varied in thickness. The CCZ was missing in 13 of the 23 areas, even in some areas that appeared normal macroscopically and were microscopically covered by intact soft tissue. Thus, in areas with a radiologic erosion the macroscopic and microscopic appearance differed between the condyle and the temporal component. The nature of the findings is discussed. PMID- 1604972 TI - Optokinetic and vestibular interactions with smooth pursuit: psychophysical responses. AB - The effect was evaluated in normal subjects of the subjective perception of motion of a small visual target (VT) when combined with the effect of vestibular stimulation produced by different magnitudes of constant angular accelerations in the dark or the effect of optokinetic stimulation produced by different constant velocities of rotation. The visual target appeared to the subject to travel more slowly and for a shorter duration when it moved in the direction of the body's angular acceleration or against that of the optokinetic drum. The perceived error in motion was: (i) in the same direction as the subject's motion sensation produced by either of the two stimuli, and (ii) quantitatively related, although differently, to the magnitude of each of the two stimulus modalities; an heuristic model is proposed to account for these observations. PMID- 1604973 TI - Cristospinal reflex in circular walking. AB - This study comprised 22 normal adults, 12 males and 10 females. Electromyograms of the bilateral gastrocnemius muscle were recorded during circular walking under two conditions: no caloric stimulation and immediately after irrigating the right auditory canal with 20 degrees C water for 20 s with the horizontal semicircular canal maintained in vertical position. With no caloric stimulation, gastrocnemius muscle activity on the right side exceeded that on the left during dextrorotation and vice versa during sinistrorotation. Following irrigation of the right auditory canal, the activity was greater on the left side than on the right during sinistrorotation, but no consistent differences in muscle activity were observed during dextrorotation. Dextrorotation was associated with ataxic gait in all cases. Thus ampullopetal lymphatic flow in the semicircular canal due to circular walking causes increased antigravity muscle tonus of the ipsilateral leg. This gives the ipsilateral leg assistance for supporting body weight which shifts to the inner side of circular walking. PMID- 1604974 TI - New immunobiological tests in the investigation of Meniere's disease and sensorineural hearing loss. AB - The aim of the study was to determine the usefulness of new immunobiological tests using fractioned human inner ear antigen in the investigation of 4 Meniere's disease and 12 rapidly progressive sensorineural hearing loss (RPSNHL). Each patient underwent a full ENT examination and a full range of immunobiological tests comprising ESR, electrophoresis, IgG, A, M, circulating immune complexes, cryoglobulins, complement, organ and non-organ auto-antibodies. The two new tests were the lymphocyte transformation test (LTT) and the immunoperoxidase test against total or fractioned human inner ear antigens. Four main bands were found in electrophoresis with the following molecular weights: 130,000, 45,000, 22,000, and 14,000. The heaviest band corresponded to IgG contained in the inner ear extract. Three cases of bilateral RPSNHL had positive LTT against inner ear antigens. No serum of patients showed a characteristics band with the immunoperoxidase test with regard to the serum of healthy subjects. At least four abnormal inflammatory non-specific tests were shown in the cases of positive LTT. Out of 3, 2 patients received steroids and improved their hearing. PMID- 1604975 TI - Intraoperative electrically evoked vestibular potentials in humans. AB - Electrically evoked short latency vestibular potentials were recorded in 9 patients during vestibular neurectomy. Patients were operated on because of intractable Meniere's disease. The VIIIth cranial nerve was exposed through a limited retrosigmoidal approach; the vestibular nerve was contacted in the cerebello-pontine angle with a bipolar platinum-iridium electrode and stimulated with biphasic current pulses (100 microseconds/phase, 0.75-1 mA p-p, 20/s). The responses were recorded over 12.8 ms between a forehead and an ipsilateral ear lobe electrode. Each recording consisted of 2 x 1,000 averaged responses. A systematically reproducible vertex-negative potential occurring at a latency of approximately 2 ms and having an amplitude of approximately 0.5 microV was recorded in all patients. This vertex-negative potential disappeared after selective vestibular neurectomy proximal to the stimulation site. Simultaneous continuous acoustic masking did not affect the response and no facial nerve response was observed on the facial nerve monitoring. These features strongly suggest that the characteristic vertex-negative potential constitutes a specifically evoked response of the vestibular system. Electrophysiological monitoring of the sectioning of the vestibular nerve during operation is one possible clinical application of intraoperative recording of electrically evoked vestibular potentials. PMID- 1604976 TI - "Floating" labyrinth. Pathophysiology and treatment of perilymph fistula. AB - Collapse of the membranous labyrinth of the pars superior is a morphological change observed in 50% of animals with experimentally produced perilymph fistula, although the extent and degree of the collapse may vary greatly. The moderately collapsed membranous labyrinth may drift with CSF and/or perilymph pressure changes and this may stimulate sensory cells of the utricle and/or semicircular canals if the sensory cells are intact and the collapsed wall is in contact with the otolithic membrane and/or cupula. This condition is termed "floating" labyrinth. Caloric irregularity is often observed in electronystagmograms recorded from animals with experimental perilymph fistula. This is also observed in patients with perilymph fistula. Partial destruction of the vestibular organs using argon laser was performed in a patient with perilymph fistula who was incapacitated because of persistent positional vertigo after closure of the oval window fistula. Irradiation of the argon laser beam was directed to the macula utriculi, utriculoampullary nerve and singular nerve. The hearing of the patient was maintained, and vertigo disappeared after laser labyrinthectomy. PMID- 1604977 TI - The ontogeny of human hearing. AB - The development of human hearing from the 26th week of fetal life to the third year post natal life is reviewed. The human fetus can perceive, react, and store auditory information from the 26th week of fetal life. This ability appears to play a role in the development of language. Infants by the 2nd to 3rd month of postpartum life have categorical perception for most phonemes whether or not these phonemes are native to their own language. The infant has a difference limen similar to that of the adult. The infant threshold is higher; the single-to noise ratio is greater in infants than adults; and the infant's temporal processing is slower than that of the adult. PMID- 1604978 TI - Development of auditory evoked potentials. AB - The development and maturation of the human auditory system appears to occur in parallel at all levels from middle ear to cortex. The maturation of evoked potentials from auditory brainstem to auditory cortex can be described by equal percentage changes in equal time periods. This is essentially the exponential growth model with equal maturation rate for each station. The auditory nerve maturation occurs at a rate considerably faster than that for more central parts of the nervous system. Premature birth does not seem to affect the maturation rate and time to maturity of the auditory brainstem potentials, so that experience does not seem to affect physiological maturation. However, there is a clear difference in maturation rates for different frequency regions, suggesting that the time course of structural maturation has an effect. Behavioral changes in hearing threshold show maturation rates similar to the physiological ones for the central nervous system. PMID- 1604979 TI - Tonotopic organization of human auditory cortex revealed by multi-channel SQUID system. AB - A 14-channel SQUID (superconducting quantum interference device) system has been used to record the magnetic signal from the human brain in response to an auditory stimuli (750, 1,000, 1,250 and 1,500 Hz, 70, 76 and 82 dB SPL, 500 ms duration). Three individuals with normal hearing were studied. The locations of magnetic response at the latency of 70 ms (P70), 100 ms (N100) and 160 ms (P160) from the onset of the auditory stimulus were identified. The location for N100 response corresponded to the primary auditory cortex (area 41), where a clear tonotopic organization was demonstrated. The amplitopic organization was less evident. These results suggest a flow of auditory signals in the temporal lobe and tonotopic organization in the auditory cortex. PMID- 1604980 TI - The effect of crossed olivo-cochlear bundle stimulation on acoustic trauma. AB - To investigate whether the crossed olivo-cochlear bundle (COCB) functions in a protective manner, albino guinea pigs were exposed to sounds of varying intensity (110-130 dB SPL, 3-30 min) with or without electric stimulation of COCB, and the threshold shifts of the compound action potential (CAP) were examined. A statistically significant protective effect was observed in animals exposed to stimuli of intermediate intensity which induce threshold shifts of 50 to 55 dB on average. No protective effect was observed in the groups exposed to greater or milder stimuli. These results are discussed in the light of the available literature. PMID- 1604981 TI - Influence of spontaneous otoacoustic emissions (SOAE) on acoustic distortion product input/output functions: does the medial efferent system act differently in the vicinity of an SOAE? AB - Otoacoustic emission (OAE) generation mechanisms reside in the active micromechanical properties of the organ of Corti, and especially in the outer hair cells (OHCs). OHCs are strongly innervated by medial efferent olivo-cochlear fibres. Decrease of the intensity of transiently evoked otoacoustic emissions (TOAEs) and modification of spontaneous otoacoustic emissions (SOAEs) during acoustic stimulation of the contralateral ear have already been shown in humans. Similar results were obtained in guinea pigs with a decrease of 2F1-F2 acoustic distortion products (DPOAEs) and a suppression of the effect with sectioning of the floor of the fourth ventricle. The present study sought to investigate the influence of contralateral auditory stimulation on DPOAEs recorded in humans. It shows a decrease in DPOAE intensity for all frequencies, at levels above 45 dB SPL of contralateral broad band noise. This effect was found at levels of contralateral BBN well below the acoustic reflex threshold, and in subjects without acoustic reflex. Moreover, the influence of transcranial transmission could be ruled out since no effect was found when contralateral BBN applied to the altered ear of totally unilaterally deaf patients. Thus, the contralateral acoustic stimulation effect on DPOAEs provides a new means of functional exploration of the medial efferent system in humans. The effect obtained is more ample at low primary frequency levels. Moreover, as DPOAEs are known to be stronger and to show more irregular input/output function patterns in the vicinity of an SOAE, the influence of contralateral auditory stimulation was studied for DPOAEs recorded at 10 Hz, 50 Hz and 150 Hz from an SOAE frequency. PMID- 1604982 TI - Cochlear microphonics and recruitment. AB - In this study, bilateral cochlear microphonics (CM) were evoked by tone burst simultaneously. A speaker was put in head-food axis 2 m from the mid-point of a given line connecting the bilateral external meatus. Five normal persons and 68 cases (34 cases of Meniere's disease, 27 cases of sudden hearing loss, and 7 cases of low-tone sensory hearing loss without vertigo) with unilateral sensory hearing loss and recruitment, in addition to 2 cases of bilateral Meniere's disease with recruitment were examined. CM shifted in normal and hearing loss ears and was absent in profound and totally deaf ears. When recruitment was present, CM at corresponding frequencies were enlarged and prolongated in 60 cases. Some of the enlarged and prolongated CM decayed slowly, others quickly. Meanwhile the CM of the opposite normal ear decreased obviously. The presence of enlarged and prolongated CM may indicate an increase of abnormal excitability of the hair cells caused by some pathological stimulations. This would cause excitability of the hair cells in the opposite cochlea to be inhibited by the effect of the efferent system. In such a condition, the patients complained that the stimulating sound was heard louder in the disordered ear than that in the opposite normal ear. CM was slightly enlarged during sleep. PMID- 1604983 TI - On the capability of the vestibular apparatus to perceive sound stimuli. AB - This paper discusses the capacity of sound perception in 5 profoundly deaf subjects in whom a "fenestra" was previously formated on the lateral semicircular canal. The ability of sound and vibration perception after fenestra formation in profoundly deaf subjects with normal function of the vestibular apparatus has been described previously. The experiments for this procedure were done on pigeons by Wit & Bleeker. The subjects aged from 22 to 34 years. Causes of deafness varied. Their hearing threshold was bilaterally higher than 95 dB HL and their vestibular apparatus was of normal excitability bilaterally when tested with a caloric test. In all 5 patients the ear conduction hearing threshold remained the same, but the ability of vibration perception improved significantly, and ranged postoperatively between 30 and 45 dB HL. The frequency dynamic range was from 125 to 2,000 Hz in 4 subjects, and from 125 to 4,000 Hz in 1 subject. The patients claimed to have perceived higher intensities, but with a variable dynamic range from frequency to frequency. The intensity range amounted to between 15 and 40 dB. The obtained data of vibration perception ability are discussed. PMID- 1604984 TI - Hearing improvement achieved by different cochlear implantation techniques on the same and contralateral ears. AB - The authors have performed cochlear implantation since 1985. Different implantation techniques have been used: extracochlear, round window and intracochlear implantation combined with different receivers. Right at the beginning, the 8-channel extra-cochlear implant produces good results due to the gradually increasing current needed to obtain the same effectivity (transduction energy). However, no great differences can be observed in speech reception whether round window or intracochlear implants be used. In addition to audiological results, we briefly outline surgical implantation techniques and implant fixation methods and summarize the outlook for long-term cochlear implantation. Six months after operation, contralateral hearing was observed. The hearing presented itself at one or two frequences. PMID- 1604985 TI - Clinical results of a 15-filter digital auditory prosthesis using selective amplification and compression. AB - Classical hearing aid efficiency was compared with that of a 15-filter digital auditory prosthesis in 23 patients suffering from partial sensorineural hearing loss. This device contains a microprocessor 320C25 from TEXAS Instruments. The sound signal is analysed at a sampling rate of 16 kHz. With the use of a Fast Fourier Transform (FFT), it provides the system with 15 energy levels at frequencies ranging from 0 to 8 kHz. The energy of each frequency band is multiplied by a coefficient stored in the device memory and directly dependent on the patient's audiometric specificities. The 15 signals are then synthesized by inverse FFT and mixed in a loudspeaker. The prosthesis is a rechargable battery powered 4 x 10 x 15 cm box programmable through a PC. The clinical results obtained with this 15-filter digital prosthesis are discussed and compared with the performances of present classical hearing aids. PMID- 1604986 TI - Preservation of hearing in bilateral acoustic neurinomas by deliberate partial resection. AB - With the aim of preserving hearing, 20 acoustic neurinomas in 17 patients with neurofibromatosis 2 were intentionally submitted to an incomplete (80%) tumour removal. In 12 cases this was an operation on the last hearing ear with total deafness of the contralateral ear. If an auditus existed in both ears the better hearing ear was selected for the primary intervention. Early audiological controls evidenced residual hearing in 19 of the 20 cases operated on by the enlarged middle fossa approach, which was utilized inspite of the tumour diameters being between 1 and 6 cm in the cerebello-pontine angle. The oncologic and functional follow-up over 1 to 7 years showed different patterns of slow progression of hearing loss and of persistent auditory function over 2 to 7 years. Facial nerve function was excellent in 16 of the 18 controlled cases. Continued CT or MRT imaging revealed no signaling in 2 cases, constant tumour sizes in 10 cases and slow progression in 3 cases. With regard to the importance of an auditory communication in the younger adult, the described treatment modality appears to be the first choice method. PMID- 1604987 TI - Antidepressant treatment of tinnitus patients. Interim report of a randomized clinical trial. AB - Previous studies have shown that severe tinnitus is associated with current major depression, and that tricyclic antidepressant therapy reduces tinnitus disability, at least compared to brief placebo treatment. We are completing a randomized clinical trial of nortriptyline, stratified by presence or absence of current major depression, in 100 patients with severe chronic tinnitus. Preliminary analysis of global outcome on the first 52 patients reveals that those receiving nortriptyline were more likely to feel that their drug had been helpful (74% vs. 36%, p less than 0.01), but were equally likely to report that their tinnitus was improved (37% vs. 32%, NS). So far, neither audiometric nor self-report measures of tinnitus have demonstrated statistically significant differences between active drug and placebo. Simply administered visual rating scales, if externally-referenced, correlated better with global outcome than did the Iowa Tinnitus Handicap Questionnaire. As expected, nortriptyline was significantly superior to placebo with respect to reductions in the Hamilton Depression Scale, especially in depressed patients. Paradoxically, depressed patients reported more disability and loudness on all scales, but had lower 1 kHz tinnitus intensity matches and dynamic ranges. Our preliminary conclusions are that: 1) nortriptyline reduces depression in patients with severe tinnitus, 2) placebo effects are very important in the treatment of tinnitus, 3) depression may be associated with decreased tolerance for both internal and external sounds, and 4) it is still difficult to specify the appropriate measures of tinnitus loudness and disability for use in therapeutic trials. PMID- 1604988 TI - Stiffness, compliance, elasticity and force generation of outer hair cells. AB - Isolated outer hair cells (OHCs) were partially sucked into especially designed cell capillaries allowing an experimental reconstitution of the cells' electroanatomy. The experimental approach separated the apical from the basolateral parts of the cells thus forming an artificial scala media and scala tympani. Resistance between both was 121 +/- 42 M omega. A sequence of negative and positive pressures was applied to the basal cell pole allowing "pulling" or "pushing" of the sensory cell investigated. The resulting length changes together with the known pressures allowed the estimation of an actual longitudinal compliance of 354 +/- 35 m/N. Following "pulling" OHCs tended to resume their initial shape after the force had ceased to be effective indicating elastic distortions. The calculated elasticity modulus of OHCs amounted to 6.1 +/- 3.4 kN/m2. From this data an actual longitudinal whole cell stiffness of OHCs of 3 x 10(-3) N/m was calculated. Ultrasound scanning of immobilized OHCs identified the cuticular plate (CP) and a central core between CP and basal cell pole as structures contributing to the cells' acoustic stiffness. Changes of the potential differences between the artificial scala media and scala tympani resulted in active length changes following the command voltage with a slope of delta 1/(1 x U) = 0.055 V-1. Assuming the validity of Hooke's law, the force generation associated with the active length changes can be calculated since the compliance is known.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1604989 TI - Development of neurosensory structures in the human cochlea. AB - The present paper summarizes the main stages in the maturation of the cochlear neurosensory structures in humans. New trends in the field of the functional development of the cochlea, as well as some recent experimental data are also discussed. PMID- 1604990 TI - The effect of anaphylatoxin component on inner ear damage. AB - It has already been reported that anaphylatoxin (AT) is closely related to inner ear lesions. In this study the pathology of inner ear damage caused by AT was investigated in Hartley strain and C4 deficient guinea pigs (C4D-GP). Although the biological activity of C3a and C5a is strong, it is of short duration, and the resulting ear damage is considered to be reversible. Because of the cellular degeneration caused by this slight damage, the damage owing to continuously activated C4a is thought to be irreversible, that is, atrophy in the stria vascularis, degeneration and sloughing of the cochlear neurons, and stretching of Reissner's membrane, and C4a is therefore considered to be requisite for the manifestation of inner ear damage. PMID- 1604991 TI - Kinetics of gentamicin in cochlear hair cells after chronic treatment. AB - Presence of gentamicin (GM) in cochlear hair cells was detected by immunohistochemistry in guinea pigs (GPs) cochlea 1, 9 and 41 days after a 6-day treatment with GM at 60 mg/kg/day (s.c.). The number of GPs in each group was respectively 7, 12 and 6. Twelve other non-treated GPs served as controls. Cochlear function was measured, just before sacrifice, by VIIIth nerve compound action potential (CAP) audiograms. Functional and immunohistological evaluations were performed by two independent naive observers respectively. Functional changes were minimal: only one out of the 25 treated GPs, from the 41-day group, showed significant threshold elevations on high frequencies. Meanwhile GM labelling was observed in most outer hair cells (OHCs) from the three rows of all the treated GPs, with radial and longitudinal gradients, and found similar in the 3 groups. These results 1) confirm that GM is significantly present in OHCs before the development of ototoxicity and 2) indicate that GM accumulates and is maintained inside the OHCs for very long periods of time, i.e. that its clearance from the hair cells, if any, would be very slow. PMID- 1604992 TI - Comparative ototoxic potential of hyaluronic acid and methylcellulose. AB - In experimental animal studies, exogenous hyaluronan (HA) has been shown to exert beneficial effects on the healing of tympanic membrane perforation. As any other exogenous substance, HA may prove potentially toxic, by filling the middle ear cavity, to the sensory cells of the organ of Corti. Electrophysiological (ABR) and morphological studies were carried out in the rat to examine the auditory function and the structure of the sensory epithelium. Rats received either HA or hydroxy-propyl-methyl-cellulose by trans-tympanic injection (middle ear cavity was completely filled up) and were compared to untreated, age- and weight-matched rats. In both treated groups ABR revealed transitory, mild conduction hearing loss, in particular for high frequencies, until day 7 postinjection. This loss recovered completely within the 15th day. Morphologically, no significant degenerative/necrotic lesions were observed in the organ of Corti, from both treated groups. PMID- 1604993 TI - Morphometric analysis of the cochlear nerve in man. AB - Fiber diameters were analyzed in the meatal segment of the cochlear nerve from 7 temporal bones obtained from 7 patients. Two patients had normal hearing for their age. Two had sustained noise exposure and one had presbyacusis of predominantly neural type. The cochleae displayed characteristic degeneration patterns. The other two manifested hearing loss of unspecified type. The fiber diameters ranged from 0.5 to 11 microns. The diameter distribution was unimodal in all seven nerves. The means of the diameters ranged from 4.2 to 5.5 microns. They were significantly different between patients with age-related normal hearing on the one hand and patients with noise induced hearing loss and neural presbyacusis on the other. The findings are discussed in relation to changes in nerve conduction speed and hearing loss; a possible correlation between the fiber diameter distribution and the tonotopical arrangement of the cochlea is suggested. PMID- 1604994 TI - Nerve growth factor stimulates neurite regeneration but not survival of adult auditory neurons in vitro. AB - Injury to either the peripheral or central nervous system results in the accumulation of growth factors at the wound site. Some of these growth factors have been shown to participate in the neural repair process. Adult auditory neurons grown in dissociated spiral ganglion cell cultures are injured (i.e. bilateral axotomy) as a result of the initial preparation of these cultures. Therefore, cell cultures of dissociated spiral ganglia provide a model for the study of repair processes of adult auditory neurons (e.g. effects of exogenous growth factors on the process of neuritogenesis by injured neurons). Auditory neurons do not survive in these dissociated ganglion cell cultures when only exogenous NGF is added to the defined culture medium. Previous work has identified substrate bound basic fibroblast growth factor (bFGF) as a survival factor for adult auditory neurons in vitro. Auditory neurons cultured on substrate bound bFGF also do not show increased survival in response to the addition of increasing concentrations of nerve growth factor (NGF) to the defined medium. This is in sharp contrast to the pronounced neurite outgrowth-promoting effects (concentration dependent) observed when exogenous NGF is added to adult auditory neurons cultured on substrate bound bFGF. We propose that several neuronotrophic factors (e.g. TGFB1, bFGF, NGF and other neurotrophins) are active in the spiral ganglions' response to injury. Several of these growth factors (i.e. bFGF, NGF) act in cooperation to promote the regeneration or repair of severed or traumatized neuritic processes. PMID- 1604995 TI - Secretion of endolymph by the isolated frog semicircular canal. AB - Secretion of endolymph is localized in some structures of the inner ear, namely the stria vascularis in the cochlea and the dark cells in the vestibule and in the lower vertebrate inner ear. In isolated semicircular canal it is possible to study separately the endolymphatic composition in the ampulla, which contains the dark cells, and in its non-ampullar part, which is devoid of these cells. Further, in vitro preparation of the semicircular canal provides access to both faces of the epithelium so that different agents can be applied separately to the apical or to the basolateral membranes of the epithelium. In this structure, the following results were obtained: i) in vitro, the semicircular canal secreted a K rich, positively polarized fluid; ii) this fluid was secreted only in the ampulla of the semicircular canal; iii) the secretion of endolymph was dependent on basolateral Na+, K(+)-ATPase, inhibited by ouabain, and basolateral Na-K-Cl co transporter, inhibited by bumetanide; iv) approximately 60% of luminal Na absorption occurred across a luminal Na channel inhibited by amiloride; v) the permeability of the paracellular pathway of the semicircular canal epithelium was 7.10(-7) cm/s. These results indicate that endolymph secretion involves basolateral Na+, K(+)-ATPase and Na-K-Cl co-transporter. An Na channel has been shown at the apical membrane. PMID- 1604996 TI - Immunohistochemical characterization of the human endolymphatic sac and its associated cell populations. AB - The use of monoclonal and polyclonal antibodies as specific markers for the localization of tissue constituents in situ allows the characterization of cells according to their state of differentiation and the detection of cellular antigens related to the function of cells and tissues. Our studies focus on the immunohistochemical characterization of the human endolymphatic sac (ES) and its associated cell populations. A panel of 37 monoclonal and polyclonal antibodies were used on frozen sections and fixed material from 64 ES of 32 persons without any clinically known inner ear disorders. The ES were removed at the time of autopsy; case histories were available. The results of our studies on the extraosseous part of the human ES support the assumption that the epithelium is metabolically active and capable of both secretion and absorption. The reactivity of the epithelial cells with antibodies against neuron specific enolase, chromogranin and somatostatin, respectively, implies a paracrine activity of the ES. Further results obtained with antibodies specific for cells of the immune system indicate a possible role of the human ES in the inner ear immune defence and a functional relationship of the ES to the common mucosa-associated immune system. PMID- 1604997 TI - The perilymphatic hypertension syndrome. AB - Perilymphatic hypertension is usually related to gushers which occur in the operating room when the stapes footplate is punctured or removed. These patients present defects in the modiolus, or enlarged cochlear aqueducts, which allow easy access of spinal fluid to the perilymphatic space. This syndrome was detected in children and appears to present consistent audiological patterns. They present a mixed hearing loss and in spite of the presence of an air-bone gap the stapedial reflexes are present. These children benefit from the use of hearing aids but show very little insertion gain in the low frequencies when tested with real-ear measurements. PMID- 1604998 TI - Magnetic facial nerve stimulation in Bell's palsy. AB - The transcranial magnetic stimulation (TMS) technique makes it possible to stimulate the intracranial part of the facial nerve. In a total of 51 patients with acute Bell's palsy, TMS was performed, and the responses were compared with those elicited by conventional extracranial electric stimulation (EES). Clinical recovery was evaluated at 258-539, mean 410, days from the beginning of the palsy. With both techniques the motor evoked potentials (MEPs) could always be elicited on the healthy side, the mean latency being 4.7 ms with TMS and 3.7 ms with EES. In the acute phase, TMS elicited MEPs on the paralyzed side in 47% of the patients, and EES in 98%. The patients with TMS elicitable MEPs during the first 4 days of the palsy had significantly better recovery than those without response (p less than 0.05). The difference in recovery between patients with or without elicitable TMS responses on days 5-8 and 9-14 was not significant. In EES, the amplitude difference between the two sides within the first 4 days was not significantly (p greater than 0.05) different. On days 9-14 the patients with a less than 80% difference between the two sides recovered significantly (p less than 0.05) better than those with a difference of greater than or equal to 80%, So, TMS may be of help in the early prognosis of Bell's palsy. PMID- 1604999 TI - A microanalytical study on human auditory ossicles in normal and pathological conditions. AB - A microanalytical study of human auditory ossicles was performed in 11 normal adults, 13 infants, 13 foetuses, 7 middle ear cholesteatoma, 7 chronic otitis and 1 facial nerve schwannoma. Malleus and incus ossification is initiated in the foetal period, the Ca/P ratio reaching a value of 1.8-1.9 in the 29-gestation week foetus and continues in the infant period until adult, except for the marginal area of the malleus head which appears mineralized in the infant. The normal Ca/P ratio for malleus is 2.10, and 2.19 for incus. In the stapes, mature Ca/P ratio values (2.11) appear in the footplate of the 23-gestation-weeks foetus. Stapes ossification continues in its head and crura, but never reaches malleus and incus values. We have confirmed that there is a relationship between Ca/P ratio and sulphur values in the ossification process; so when the first increases the second decreases. Finally, in our pathological material we have not found any significant alteration of Ca/P ratio, sulphur or other elements studied. PMID- 1605000 TI - Problems in alloplastic middle ear reconstruction. AB - Alloplastic materials have been used in middle ear reconstruction since 1952. Biologically, biomaterials and specifically ceramics can be defined as being bioinert, bioactive or biodegradable; these terms being descriptive of the biochemical response provoked by the material in the host tissue. Various ceramics, carbons and polymers and their reactions have been studied by the author and his colleagues over the past 5 years utilising animal implantation and fibroblast culture studies aligned with experience from clinical usage. The qualities of the ideal alloplastic implant namely: biocompatibility, stabilisation and incorporation, the consistency of the implant and bioactive bonding and the biofunctionality or mechanics, are applied to the materials currently available. No single alloplastic material fulfills all criteria, the problems encountered in relation to the biomaterials are reported. A better understanding of the microstresses, fatigue and microfractures is necessary, before the ideal alloplastic biomaterial becomes available. PMID- 1605001 TI - Histopathology of spontaneous brain herniations into the middle ear. AB - Two patients with spontaneous brain herniation into the middle ear have been operated on with a combined otoneurological approach. In case No. 1, two 2 x 3 mm arachnoid tissue herniations were found in the tegmen antri of the left ear. Six years later, a 8 x 9 mm mass consisting of prolapsed brain was removed from the right ear. The histological examination showed normal but disorganized nervous tissue. The surface consisted of middle ear mucosa or modified glial cells. More deeply numerous well preserved neurons and synapses were observed. In case No. 2, a 2 x 1 cm herniation was found in contact with the ossicles and the bony walls of the middle ear. The herniation consisted of partly degenerated nervous tissue which could explain the episode of temporal lobe seizure the patient experienced 8 years before surgery. In the world literature during the last 40 years, 29 cases of spontaneous or idiopathic brain herniation into the middle ear and mastoid have been reported. In 10, the herniations were multiple, as in our case No. 1. Case No. 1 is interesting also because the spontaneous brain herniation was bilateral. PMID- 1605002 TI - Respiratory tract viruses in otosclerotic lesions. An immunohistochemical study. AB - A series of viral antigens, including adenovirus, influenza A and B, parainfluenza types 1 and 3, measles, mumps, respiratory syncytial (RSV) and Epstein Barr (EBV) viruses was studied in a prospective series of stapes specimens from 24 consecutive patients operated on for otosclerosis. The stapes specimens were processed for light microscopy and immunohistochemistry. With the exception of one case of positive specific reactivity for anti-RSV antibody in one multinuclear osteoclastic cell, no specific reactivity was seen in the specimens. This was the case both in active (n = 8) and inactive (n = 16) otosclerotic lesions. The possibility of unspecific staining reactions is discussed. PMID- 1605003 TI - The effect of ammonia on the respiratory nasal mucosa of mice. A histological and histochemical study. AB - The effects of prolonged exposure to ammonia vapour on the histological pattern and enzymatic activity of the respiratory nasal mucosa of 75 adult male mice were investigated and compared with a control group. In the exposed animals, the nasal epithelial cells showed patches of squamous metaplasia, dysplasia, and even malignant changes in the nose of 2 animals. As regards the histochemical changes, the apical border of epithelial cells showed increased succinic dehydrogenase activity denoting increased energy production. The acid phosphatase activity was also higher, and this seemed to be a constant feature in metaplastic and neoplastic transformation. The alkaline phosphatase activity was detected only in the basal parts of epithelial and goblet cells, which was attributed to an increased activity of basal cells to form a thicker basement membrane. The periodic acid Schiff's reaction was weak in the cilia due to their partial degeneration. Prolonged exposure to ammonia interfered with the normal physiological mucociliary action resulting in accumulation of particulate matter initiating or promoting a neoplastic process. PMID- 1605004 TI - Neuropeptides in human salivary (submandibular and parotid) glands. AB - The existence, distribution and density of various neuropeptides in human submandibular and parotid glands were investigated using immunocytochemistry and radioimmunoassay. Numerous nerve fibers containing vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM), or neuropeptide Y (NPY) and C-flanking peptide of NPY (CPON) immunoreactivities (ir) were found in close association to acini, ducts and blood vessels. Only few calcitonin gene-related peptide (CGRP)- and substance P (SP)-ir nerve fibers could be demonstrated, mainly localized around blood vessels and ducts. Galanin and the newly discovered peptides helospectin and pituitary adenylate cyclase activating peptide (PACAP) could not be detected in human salivary glands. PMID- 1605005 TI - Pattern of gross displacement of the vocal fold in adduction and abduction movements. AB - The pattern of gross displacement of the vocal fold during adduction and abduction was studied in 4 adult fresh human larynges (2 males and 2 females). Markers were placed on specific sites along the edge of the vocal fold. Preliminary observations showed upward and lateral movement of the free edge during abduction. The vocal fold as a whole glides into and fills the cavity of the laryngeal ventricle. To quantify this observation 14 larynges (8 males and 6 females) were studied, using a technique designed to measure vertical and horizontal displacement of the vocal fold. An average of a 1.34 mm elevation and 4.43 mm lateral excursion were observed at midvocal fold level. A model for studying the pattern of vocal fold abduction is suggested and discussed. PMID- 1605006 TI - Recurrent nerve/ansa cervicalis nerve anastomosis: a treatment alternative in unilateral recurrent nerve paralysis. AB - Sectioning of the right recurrent nerve was done in 5 mongrel dogs under general anaesthesia. The distal stump was anastomosed with the ansa cervicalis nerve branch to the sternothyroid muscle. Three to 5 months later the vocal cord movements during light and very light anaesthesia were videorecorded. Under light anaesthesia contraction and medial bulging of the reinnervated right vocal cord occurred in 4 of the dogs. Under very light anaesthesia there was also some adduction of the right vocal cord in these 4 dogs. The right recurrent nerve was then sectioned proximally to the anastomosis and stimulated electrically. In all 5 dogs we observed that electrical stimulation produced a strong adduction of the right vocal cord. Histochemistry of the right vocal and posterior cricoarytenoid muscles showed that reinnervation had taken place. The study indicates that in cases of unilateral vocal cord paralysis an anastomosis between the ansa cervalalis and the recurrent nerve will result in improved phonatory function of the affected vocal cord. PMID- 1605007 TI - Biochemical analysis of vocal fold polyps. AB - Arachidonic acid metabolites (AAm) have important regulatory functions within several areas of otorhinolaryngology: modulation of immune and allergic responses, inflammation, allergy, etc. The aetiology of vocal fold polyps is still obscure as are the possible mechanisms responsible for their forming and developing. The aim of this study was therefore to investigate the relationship between release of prostaglandins (PGE2, PGI2) and tromboxans (TxA2) from vocal fold polyps ex vivo in 21 patients, in comparison to normal airway mucosa. The production of PGE2 by vocal fold polyps was less than in the controls (ng/ml) (0.5 +/- 0.54; n = 21 vs. 1.09 +/- 0.78; n = 21) (p less than 0.05) but higher than in nasal polyps (0.14 +/- 0.11; n = 16) (p less than 0.01). Prostacyclin production by vocal fold polyps (0.99 +/- 0.92) was less than in control mucosa (2.24 +/- 1.93) (p less than 0.01), but higher than by nasal polyps (0.26 +/- 0.14) and less than in controls (0.99 +/- 0.73) (p less than 0.01) or nasal polyps (0.52 +/- 0.04) (p less than 0.01). PMID- 1605008 TI - The influence of ageing on wound healing of the cricoid. AB - In young and adult rabbits the effects of one anterior or two bilateral splits of the cricoid were studied. Interruption of the cricoid ring elicits wound healing of the cut edges and induces changes in form and size of the separated parts of the cricoid (indirect effect). It was demonstrated that with increasing age i) the wound healing capacities of the hyaline cartilage is highly diminished or lost and ii) the induced remodelling, involving the total ring in young animals, is in the adult stage confined to the posterior part. Moreover, the observations suggest that dividing the cricoid ring in an anterior and posterior part at a young age can result in a stimulation of growth of the anterior part, in comparison with unoperated control animals. PMID- 1605009 TI - Electromyography of cricopharyngeal muscles in patients with oesophageal speech. AB - Subject for the examination were 30 patients who during total laryngectomy had had two silver clips for haemostasis inserted into the cricopharyngeous muscle about 3 cm from the sewing place in the midline, facilitating the location of the muscle and the placing of a needle electrode. Twelve to 18 months after laryngectomy and phoniatric rehabilitation, electromyographic examinations were performed. Each EMG recording was evaluated as to amplitude, discharge frequency and time duration of muscle electric activity. EMG recordings made during deglutition and phonation proved dependences of cricopharyngeous muscle activity on quality of oesophageal voice production and higher activity of muscle during phonation than deglutition in patients who developed very good and good oesophageal speech. PMID- 1605010 TI - Interleukin 2 receptors on squamous cell carcinomas of the head and neck. Characterization and functional role. AB - IL2Rs, in the presence of IL2, mediate activation and proliferation of human normal lymphocytes and modulate functional changes of some human leukocytic malignancies. IL2Rs have been demonstrated also on human neoplastic and fetal non hematologic cells in vitro, although their functional role has not been described. We describe the presence of high affinity IL2Rs on squamous cell carcinoma of the head and neck (SCCHN) lines in vitro. Expression of 200 binding sites for IL2 with an affinity of 17 x 10(-12) was demonstrated by radiobinding experiments. When cytocentrifuged SCCHN cells were studied by immunoperoxidase staining, strong positive staining was repeatedly obtained using a monoclonal antibody to the p70 subunit of the IL2Rs. Experiments in vitro and in vivo, in a nude mouse model, showed a functional role for these receptors. In fact, low doses (8-500 U/ml) of IL2 were able to inhibit growth of 11 of the 16 SCCHN lines tested. Our observations may have broad implications for the immunotherapy of cancer in general, showing the complementary immunomodulatory and direct effects of IL2. PMID- 1605011 TI - Using Cox's proportional hazards model for prognostication in carcinoma of the upper aero-digestive tract. AB - One of the major short comings of the traditional TNM system is its limited potential for prognostication. With the development of multifactorial analysis techniques, such as Cox's proportional hazards model, it has become possible to simultaneously evaluate a large number of prognostic variables. Cox's model allows both the identification of prognostically relevant variables and the quantification of their prognostic influence. These characteristics make it a helpful tool for analysis as well as for prognostication. The goal of the present study was to develop a prognostic index for patients with carcinoma of the upper aero-digestive tract which makes use of all prognostically relevant variables. To accomplish this, the survival data of 800 patients with squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx or larynx were analyzed. Sixty-one variables were screened for prognostic significance; of these only 19 variables (including age, tumor location, T, N and M stages, resection margins, capsular invasion of nodal metastases, and treatment modality) were found to significantly correlate with prognosis. With the help of Cox's equation, a prognostic index (PI) was computed for every combination of prognostic factors. To test the proposed model, the prognostic index was applied to 120 patients with carcinoma of the oral cavity or oropharynx. A comparison of predicted and observed survival showed good overall correlation, although actual survival tended to be better than predicted. PMID- 1605012 TI - Relationship between "dynamic histology" and metastases of laryngeal tumors. AB - The clinical characteristics of laryngeal cancer, its site and extent, determine the incidence of regional metastases. However, data have also shown that lymph node involvement is influenced by the degree of malignancy of the tumor. In the course of histoautoradiographic processing of 79 laryngeal tumors and a 5-8-year follow-up study of the patients, a correlation between proliferative activity and incidence of metastasis was found. Well differentiated tumors with low proliferative activity rarely metastasized whereas in cases of slightly differentiated tumors of strong proliferative activity the occurrence of manifested or occult metastases should always be taken into consideration. The state of the lymph node determines decisively the prognosis and treatment of laryngeal cancer. In some cases, preventive interventions may improve the therapeutical results in seriously endangered patients. PMID- 1605013 TI - Ultrastructural changes in contralateral superior vestibulo-ocular neurons one year after vestibular neurectomy in the cat. AB - Twenty contralateral superior vestibulo-ocular neurons (SVON) from 3 cats were studied morphologically one year after a right vestibular neurectomy. Eighteen SVON contained a smooth or slightly crenated nuclear membrane, a 63% loss of synaptic profiles (SP) and a 22% decrease in size compared to control SVON. Two cells contained nuclear membrane invaginations, a 40% loss of SP and a 31% size decrease compared to control SVON. The volume fractions of rough endoplasmic reticulum and ribosomes were decreased in these two cell groups but no change was noted in Golgi apparatus and mitochondria. These contralateral SVON reached a size, innervation density and content of organelles similar to ipsilateral SVON at one year following vestibular neurectomy. PMID- 1605014 TI - TNM classification of the larynx. PMID- 1605015 TI - Biology of cancer invasion and metastasis. AB - Current concepts of invasion eventually leading to metastasis are discussed and exemplified by cancers of the head and neck mucosa. Invasion occurs at a number of steps, each step making an ecosystem comprising not only the neoplastic cells but also their normal counterparts, a variety of host cells and the extracellular matrix. The ecosystem concept may explain aspects of metastasis such as site dependence and organ-specificity of cancer metastasis as well as invasiveness of normal leucocytes. Genes implicated in invasion and metastasis are actively searched for. Recently, the epithelial cell-cell adhesion molecule E-cadherin has been identified as an i- (invasion suppressor) gene product, i.e. a molecule the expression of which counterbalances i+ (invasion promotor) gene activity. Downregulation of E-cadherin in human head and neck cancers may account for their invasive and metastatic behaviour. PMID- 1605016 TI - Premalignant laryngeal lesions. AB - Premalignant laryngeal lesions are classified into three classes according to the degree of atypia present: class I mild dysplasia, class II moderate dysplasia and class III severe dysplasia and carcinoma in situ. The risk that a carcinoma may develop later increases in the successive classes. The lesions are almost exclusively localized on the vocal cords. It is mandatory to remove the whole lesion for histopathological examination. A close cooperation between pathologist and laryngologist is necessary. progress in the development of more subjective and reproducible methods of grading is being made. Patients with class I and class II lesions are merely followed after an excisional biopsy. There is not a single best treatment modality for class III lesions. Radiotherapy has proven to be effective. However, the concept of microsurgical removal of the complete lesion seems to enable a more conservative approach for this class as well. PMID- 1605017 TI - Metastases of carcinoma of the larynx. AB - The status of the cervical lymph nodes is the single most important prognostic factor in head and neck cancer, and the management of metastatic disease plays an important role in the treatment of carcinoma of the larynx. Clinical assessment of the neck is not very accurate, and the role of newer imaging techniques such as CT, MRI and Ultrasound guided Fine Needle Aspiration Cytology is being assessed, in order to improve upon the results of clinical palpation alone. The site of the primary tumour within the larynx is an important factor in affecting the frequency and the pattern of lymph node metastases to the neck. Indications for the use of surgery and radiotherapy for the elective and therapeutic management of lymph node metastases of carcinoma of the larynx are discussed with reference to the various sites of the primary tumour. PMID- 1605018 TI - Second primary tumours in laryngeal cancer. AB - Second primary tumours develop in 3.8-20.5% of patients with laryngeal cancer. 2.2-15.3% of those occur in the upper aerodigestive tract, 1.1-12% in the lungs. More second tumours occur in supraglottic than in glottic cancer and more in males than in females. Both tobacco and alcohol are important risk factors. Second primary tumours usually carry a bad prognosis. Two approaches are possible to combat the problem: early detection and (chemo-)prevention. The largest chemoprevention study in head and neck cancer patients is EUROSCAN. Preliminary data of the study will be presented. PMID- 1605019 TI - Imaging of laryngeal cancer. AB - Currently CT and MR are the most competitive modalities in the study of laryngeal cancer. Both radiological techniques are used to define the deeper extent of the disease and to look for disease in the blind mucosal areas. They allow evaluation of the exact extent of the tumor and this information is indispensable when one has to decide if a patient is candidate for speech conservation surgery, if a patient can be treated by radiation alone etc. MR is preferred in cooperative patients because it allows multiplanar imaging and provides the best soft tissue definition, both resulting in a more exact staging. Moreover cartilage involvement is best evaluated on MR images. CT is used when the patient has major problems with secretions, is not cooperative, has respiratory problems and when MR is not available. MR and CT are also helpful in the detection of recurrent tumor in postoperative patients but are far less reliable in the distinction between "residual or recurrent tumor" and "fibrosis or edema" in irradiated patients. PMID- 1605020 TI - Carcinoma of the larynx. Surgery: general aspects. AB - A necessary and adequate selection of operations capable of meeting all the indications involved by partial surgery, is required. We suggest such a selection inspired on that of 1983. Partial laryngectomies for glottic carcinoma: CO2-laser endoscopic cordectomy, fronto-lateral partial laryngectomy (LEROUX-ROBERT), hemiglottectomy (GUERRIER), anterior partial laryngectomy with epiglottoplasty (TUCKER), subtotal laryngectomy with cricohyoidoepiglottopexy (MAJER-PIQUET). Partial laryngectomies for supraglottic carcinoma: horizontal supraglottic laryngectomy (anterior approach), CO2-laser endoscopic epiglottectomy, lateral supraglottic pharyngo-laryngectomy (ALONSO), subtotal laryngectomy with cricohyoidopexy (LABAYLE). Total laryngectomy As from the early eighties onwards, the great progress in vocal rehabilitation following laryngectomy has certainly been the development of phonatory prosthesis. PMID- 1605021 TI - Radiotherapy of laryngeal cancer. General principles and results in T1 and T2 cases. AB - Radiotherapy is an effective treatment modality for early (T1-T2) laryngeal cancer, offering the patient a substantial chance of cure while preserving the anatomical integrity of the larynx. Whereas in early glottic lesions the irradiation volume can be restricted to the larynx proper, in supraglottic tumours the inclusion of the regional nodes is mandatory in view of their propensity for regional spread. Local control figures at 5 years are broadly in the range of 79% to 91% (T1) and 63% to 72% (T2) for glottic cancer and of about 75% (T1) and 50% (T2) for supraglottic cancer (N0 + N+). Net survival figures, including those patients having received salvage surgery are in the range of 80% to 98% (T1 glottic), of 60% to 90% (T2 glottic), of 82% to 100% (T1 supraglottic) and of 58% to 88% (T2 supraglottic). PMID- 1605022 TI - Treatment of advanced laryngeal cancer (T3-4). AB - Various treatment options for advanced laryngeal cancer are discussed. Although no results of prospective studies are available, combined treatment of total laryngectomy and radiotherapy seems to offer the best locoregional control rates and maybe survival rates. This, however, results in the loss of natural voice. Radiotherapy alone (RA) will result, in unselected cases, in a local failure rate of approximately 50%. However, when the radiation schedule will be tailored to radiobiological parameters like potential doubling time of clonogenic cells local control may be enhanced. The choice of treatment may be related to known prognostic factors like severe airway obstruction, sex, tumorextension and involvement of neck nodes. Since in females and in patients with tumors confined to the glottic region only local control with RA is high, primary radiotherapy is advocated. For patients with severe airway obstruction or N2-3 neck nodes, locoregional control rates with RA are poor, so surgery combined with postoperative radiotherapy is advisable. For the remaining group of patients RA may be tested against combined treatment in a prospective trial. PMID- 1605023 TI - The role of chemotherapy in the management of advanced laryngeal cancer. AB - At the time of diagnosis about half the patients with laryngeal cancer have locally advanced disease. In our series of 720 larynx carcinoma patients, treated in the department of radiotherapy at the University hospital in Ghent, in a period between 1975 and 1991, 45.2% of the patients had stage III or IV disease. The excellent results from locoregional treatment of limited disease are given elsewhere in this issue (De Schryver). Results for treatment of stage III and IV disease remain however poor. Locoregional failure rates of 50% and overall survival rates of 30% after 5 years indicate the need for better initial local and systemic control in advanced stage disease. PMID- 1605025 TI - Carcinoma of the larynx. PMID- 1605024 TI - Voice rehabilitation after total laryngectomy. AB - The surgical treatment of the larynx carcinoma has been accompanied by different techniques to restore voice and speech after total laryngectomy. A historical and contemporary review of the different voice and speech restoration methods is described. PMID- 1605026 TI - Epidemiology and etiological factors of laryngeal cancer. AB - Laryngeal cancer is a malignancy that is relatively uncommon compared to carcinomas of all organs. It refers almost exclusively to squamous carcinomas, although the larynx may be a site for all kinds of neoplasms. The incidence has a high predominance in males, but the ratio male-to-female is decreasing. Cancer of the larynx is primarily a disease of the sixth and seventh decade. PMID- 1605027 TI - Effect of cimetidine on isolated rat myocardial reperfusion injury. AB - The effects of cimetidine (Cim) on ventricular fibrillation threshold (VFT), diastolic excitation threshold (DET), effective refractory period (ERP), and vulnerable period (VP), were determined in both stable perfusion and postischemic reperfusion rat hearts. The results showed that reperfusion after 15 min global myocardial ischemia caused a significant decrease VFT and ERP, and an increase in VP and DET. Cim 1 mmol.L-1 prevented the lowering in VFT, shortening in ERP, and lengthening in VP from the postischemic reperfusion. Cim 0.1 mmol.L-1 attenuated the exacerbation of VFT and VP. Cim 0.01 mmol.L-1 did not exert any noticeable influence on the electrophysiological parameters. It was shown that Cim 1 mmol.L 1 protected myocardium against the aggravation of electrophysiological characteristics induced by postischemic reperfusion. PMID- 1605028 TI - (-)-stepholidine: a dopamine receptor antagonist shows agonistic effect on rotational behavior in 6-hydroxydopamine-lesioned rats. AB - (-)-Stepholidine ((-)-SPD), a well demonstrated dopamine (DA) receptor antagonist in normal rats, could markedly induce contralateral rotational behavior in 6 hydroxydopamine (6-OHDA)-lesioned rats. This peculiar behavioral action of (-) SPD, proposed to be an agonistic action on DA receptors, was further studied in this paper. The rotational behavior challenged by (-)-SPD (4 mg.kg-1, ip) or SKF 38393 (selective D1 agonist) had a gradually progressive process with a long latent period and a plateau response after 56-67 postlesion days. On the contrary, the action of apomorphine (APO) or D2 selective agonist N-0347, had a short latent period and a plateau response after d 21 of postlesion. In the latent period of rotation, (-)-SPD (4 mg.kg-1) was primed by pretreatment of APO (0.2 mg.kg-1, ip). In the period of steady contralateral rotation, a dose dependent action of (-)-SPD was found in a range of 0.5-8 mg.kg-1 and a linear correlation (r = 0.77, P less than 0.01) between the rotation induced by (-)-SPD (4 mg.kg-1) and by APO (0.2 mg.kg-1) was also shown. These results suggest that the agonistic effect of (-)-SPD on rotation behavior in 6-OHDA-lesioned rats resembles that of D1 agonist SKF-38393. Taken together, the dual actions of (-) SPD, antagonistic on normosensitive DA receptors and agonistic on supersensitive DA receptors, were proposed. PMID- 1605029 TI - Effects of m-nisoldipine on delayed afterdepolarization of canine Purkinje fibers. AB - Effects of m-nisoldipine (m-Nis) on delayed after depolarization (DAD) and triggered activity (TA) were studied using standard microelectrode technique. The development of DAD and TA were markedly inhibited by pre-treatment with m-Nis (1 4 mumol.L-1) as well as m-Nis treatment after DAD and TA had been elicited. The amplitude of DAD was reduced from 15.3 +/- 2.7 to 2.3 +/- 2.0 mV, and the duration from 980 +/- 45 to 130 +/- 27 ms. The occurrence of TA was also reduced or prevented by m-Nis. These effects of m-Nis might be attributed to its blocking effects on voltage-dependent calcium channel and the resultant alleviation of intracellular calcium overload. PMID- 1605030 TI - Antithrombotic activity of verapamil. AB - The antithrombotic activity of verapamil (Ver) was assessed in an arterial thrombosis model and an ex vivo thrombosis model. Ver 2 and 4 mg.kg-1 ip markedly prolonged the time of thrombotic occlusion in rat carotid artery induced by electric stimulation. The weight of thrombus formed ex vivo was reduced by Ver 0.2 mg.kg-1 iv. However, Ver showed no effects on blood viscosity. PMID- 1605031 TI - Antihypertensive effects of m-nisoldipine and nisoldipine on conscious renal hypertensive rats and dogs. AB - The antihypertensive effects of m-nisoldipine (m-Nis) and nisoldipine (Nis) by ig 0.3, 1.0, 3.0 and 1.0, 3.0, 9.0 mg.kg-1 respectively on renal hypertensive rats (RHR) and 0.1, 0.3, 1.0 mg.kg-1 orally (for both drugs) on renal hypertensive dogs (RHD) were studied. Both m-Nis and Nis depressed blood pressure (BP) dose dependently in RHR and RHD. The reduction of blood pressure correlated well with the m-Nis concentration in plasma of RHD. On the basis of ED20 (HR)/ED20 (BP), the hypotensive effect of m-Nis on systolic blood pressure (SBP) was only 1.6 times as great as that of Nis on RHR (P less than 0.05), but in RHD, both drugs showed the same potency (P greater than 0.05). In both models, m-Nis showed much more potent effect on diastolic blood pressure (DBP) than Nis (P less than 0.01), and possessed stronger hypotensive effects on DBP than on SBP (P less than 0.05 and P less than 0.01); but for Nis, its effects on SBP and DBP appeared to be in the same order (P greater than 0.05). The fall in BP was accompanied by a transient increase of heart rates (HR) with m-Nis and Nis in RHR and RHD. The chronic antihypertensive effects of m-Nis and Nis were also remarkable with 1.0 mg.kg-1 daily at 9 AM for 21 d. During this period, the BP and HR lowered to nearly normal level. After withdrawal of m-Nis and Nis, the hypotensive effects lasted nearly 1 wk. PMID- 1605032 TI - [Effects of rhynchophylline and isorhynchophylline on blood pressure and blood flow of organs in anesthetized dogs]. AB - In anesthetized thoracotomized dogs, rhynchophylline (Rhy 5 mg.kg-1, iv) reduced the mean arterial pressure (MAP), heart rate (HR), and coronary blood flow (CBF) by 1.16 +/- s 0.67 kPa, 19 +/- 12 beats/min, and 0.12 +/- 0.04 ml.min-1.g-1, whereas isorhynchophylline (Isorhy 1 mg.kg-1, iv) reduced the parameters by 3.58 +/- 0.19 kPa, 26 +/- 18 beats/min, and 0.10 +/- 0.04 ml.min-1.g-1, respectively. In unthoracotomized dogs, Rhy (10 mg.kg-1, iv) decreased renal blood flow (RBF) by 0.35 +/- 0.16 ml.min-1.g-1, but did not change the MAP. Isorhy (5 mg.kg-1, iv) reduced the MAP by 3.44 +/- 1.44 kPa, but the RBF remained unaffected. These results indicated that the hypotensive effect of Isorhy in a dosage not affecting RBF was more potent than that of Rhy. PMID- 1605033 TI - [Effects of tetrodoxin and verapamil on triggered activities induced by cesium chloride in cat heart in vivo]. AB - Cesium chloride (CsCl, 0.5 mmol.kg-1, iv) decreased sinus rate, shortened monophasic action potential duration (MAPD), and induced early after depolarization (EAD) in cat heart in vivo. Tetrodotoxin (TTX, 8 micrograms.kg-1, iv) suppressed the prolonged MAPD. TTX and verapamil (Ver, 0.5 mg.kg-1, iv) decreased the EAD amplitude and suppressed the sustained ventricular tachycardia induced by repeated injection of CsCl. These results suggested that the normal inward sodium "window" current and slow inward current (Isi) carried by calcium or sodium appear to be essential for the occurrence of EAD and triggered arrhythmia if repolarization outward potassium current are blocked. PMID- 1605034 TI - [Effects of serotonin and norepinephrine on neuronal discharges of the nucleus tractus solitarii in medullary slices]. AB - Effects of serotonin (5-HT) and norepinephrine (NE) on neuronal activities of the nucleus tractus solitarii (NTS) were investigated in rat medullary slice preparations. The spontaneous discharges after perfusion of slices with 5-HT (1 mumol.L-1, 3 min) were increased in 25 (58.1%), reduced in 13 (30.2%), and unchanged in 5 (11.7%) neurons. Afer perfusion of slices with NE (1 mumol.L-1, 3 min), the spontaneous discharges were reduced or ceased in 27 (62.8%), increased in 13 (30.2%), and unchanged in 3 (7.0%) neurons. Responding to both 5-HT and NE were 38 (88.4%) neurons, among which 21 were selected for studying the effect of ketanserin (a new 5-HT2 blocker). The spontaneous discharges were more increased in 10 (47.6%) and reduced in 4 (19.0%) neurons after perfusion of ketanserin+NE than after perfusion of NE alone. These results indicate that there is an interaction between 5-HT2 receptor and alpha 2 adrenoceptor at NTS level, suggesting that the central action of ketanserin may be one of its antihypertensive mechanisms. PMID- 1605035 TI - [Inhibitory effect of clonidine on hemolysis after thermal injury in animals]. AB - Clonidine (1 mg.kg-1, ip) inhibited hemolysis in mice and rats after burn. The effects were abolished by pretreatment with yohimbine (5 mg.kg-1, ip) but not by prazosin (10 mg.kg-1, ip). The increased osmotic fragility of erythrocytes and the elevation of plasma NE level in burned animals were markedly lowered by clonidine which also raised the glutathione level of whole blood and enhanced the activity of glutathione peroxidase. These results indicated that the action of clonidine on hemolysis was carried out by means of depression of adrenergic alpha 2 receptors and reduction of free radicals. PMID- 1605036 TI - [Effects of m-nisoldipine and nisoldipine on isolated uterine muscle]. AB - m-Nisoldipine (m-Nis) and nisoldipine (Nis) inhibited spontaneous contraction of isolated non-pregnant human myometrium, IC50 being 3.7 +/- 0.7 mumol.L-1 for m Nis and 6.0 +/- 0.9 mumol.L-1 for Nis. Both drugs also suppressed spontaneous and oxytocin-induced contraction of isolated pregnant rat uterus. In isolated uterus from virgin rat, both drugs inhibited the contractions induced by KCl, acetylcholine (ACh), and oxytocin (Oxy), the values of pD'2 against KCl, ACh, Oxy being 9.0 +/- 0.2, 6.1 +/- 0.1, and 5.9 +/- 0.1 for m-Nis and 9.1 +/- 0.3, 5.7 +/ 0.2, and 5.6 +/- 0.1 for Nis respectively. The results indicate that both m-Nis and Nis may be clinically useful for the treatment of dysmenorrhea and premature labour. PMID- 1605037 TI - [Effects of methylflavonolamine hydrochloride on contractility of isolated rabbit ileum]. AB - Methylflavonolamine hydrochloride (MFA), verapamil (Ver), and trifluoperazine (Tri) inhibited the contractions induced by submaximal concentrations of acetylcholine (ACh) and serotonin (5-HT). IC50 values (mumol.L-1) were 33.2 +/- 0.7, 0.276 +/- 0.018, 3.83 +/- 0.23, and 15.31 +/- 0.10, 0.233 +/- 0.017, 2.33 +/ 0.20, respectively. MFA, Ver, and Tri inhibited the contractions induced by CaCl2 and pD'2 values were 4.3 +/- 0.3, 6.23 +/- 0.22, 4.99 +/- 0.24, respectively. MFA 3 mumol.L-1, Ver 0.03 mumol.L-1, and Tri 3 mumol.L-1 inhibited the contractions induced by ACh in Ca(2+)-free medium, while MFA 60 mumol.L-1, Tri 30 mumol.L-1, but not Ver 0.6 mumol.L-1, had pronounced inhibitions on extracellular calcium-dependent contractions induced by ACh. These results suggest that MFA has a calcium antagonistic effect and that MFA is similar to Tri, but not Ver, in mechanism. PMID- 1605038 TI - [Influence of neural regulation on anti-arrhythmic effects of GABA in rats]. AB - In anesthetized rats, GABA 10 mg.kg-1 iv delayed the onset of ventricular premature (VP) (P less than 0.01) and ventricular tachycardia (VT) (P less than 0.01) and reduced the incidence of ventricular fibrillation (VF) (P less than 0.05). The anti-arrhythmic effects of GABA remained after cervical vagotomy, iv hexamethonium 10 mg.kg-1 or destruction of CNS. It was also seen on pithed rats. In Langendorff heart, GABA 100 mg.L-1 elevated the threshold doses of aconitine required to induce VT (P less than 0.01), VF (P less than 0.01), and heart stop (HS) (P less than 0.01). These results suggest that iv GABA counteracts aconitine induced arrhythmia directly on the heart, not related to the neural regulation. PMID- 1605039 TI - [Effects of silybin on acute myocardial infarction and reperfusion injury in anesthetized rats]. AB - The effects of silybin (Sil) on myocardial infarction size and ischemia- and reperfusion-induced arrhythmias were studied in anesthetized open chest Sprague Dawley rats. It was found that pretreatment with Sil 20, 50, and 80 mg.kg-1 iv reduced significantly infarct size by 34.7%, 35.0%, and 50.6% respectively at 4 h after ligation. Sil prevented ischemic arrhythmia only at the dose of 80 mg.kg-1. In reperfusion experiment, pretreatment with Sil 20 mg.kg-1 decreased significantly reperfusion-induced arrhythmia. PMID- 1605040 TI - Scavenging effect of catechin on free radicals studied by molecular orbital calculation. AB - The eigenvectors, net charges, and electron population on catechin were calculated with molecular orbital method MNDO. It was found that the 2 hydroxyls on the benzene ring of the chromane were more active than the others on the other benzene ring when it reacted with a free radical. PMID- 1605041 TI - Excess postexercise oxygen consumption--magnitude, mechanisms and practical implications. PMID- 1605042 TI - Influence of stretch-shortening cycle on mechanical behaviour of triceps surae during hopping. AB - Six subjects performed a first series of vertical plantar flexions and a second series of vertical rebounds, both involving muscle triceps surae exclusively. Vertical displacements, vertical forces and ankle angles were recorded during the entire work period of 60 seconds per series. In addition, expired gases were collected during the test and recovery for determination of the energy expenditure. Triceps surae was mechanically modelled with a contractile component and with an elastic component. Mechanical behaviour and work of the different muscle components were determined in both series. The net muscular efficiency calculated from the work performed by the centre of gravity was 17.5 +/- 3.0% (mean +/- SD) in plantar flexions and 29.9 +/- 4.8% in vertical rebounds. The net muscle efficiency calculated from the work performed by the contractile component was 17.4 +/- 2.9% in plantar flexions and 16.1 +/- 1.4% in vertical rebounds. These results suggest that the muscular efficiency differences do not reflect muscle contractile component efficiency but essentially the storage and recoil of elastic energy. This is supported by the relationship (P less than 0.01) found in vertical rebounds between the extra work and the elastic component work. A detailed observation of the mechanical behaviour of muscle mechanical components showed that the strategy to maximize the elastic work depends also on the force velocity characteristics of the movement and that the eccentric-concentric work of the contractile component does not always correspond respectively to the ankle extension-flexion. PMID- 1605043 TI - Myosin heavy chain isoform transition in ageing fast and slow muscles of the rat. AB - Using gradient sodium dodecyl sulphate-polyacrylamide gel electrophoresis, myosin heavy chain (MHC) isoforms were studied in the extensor digitorum longus (EDL) and the soleus muscles of male Wistar rats at different ages (5, 10, 20 weeks, 1 and 2 years). In the EDL muscle, four types of MHC isoforms were observed in all age groups. There was an increase in the percentage of HCIId and a concomitant decrease in the percentage of HCIIb with increasing age. No significant difference was observed in the percentages of HCI and HCIIa isoforms in all the age groups. In contrast, the soleus muscle contained two MHC isoforms, HCI and HCIIa. There was an increase in the percentage of HCI and a concomitant decrease in the percentage of HCIIa with increasing age. These results suggest that age related changes in the MHC isoforms in both the fast-twitch EDL and the slow twitch soleus muscles are one factor underlying the age-related decrease in the speed of muscle contraction. PMID- 1605045 TI - The first breaths of air stimulate noradrenaline turnover in the brain of the newborn rat. AB - The aim of this study was to analyse the noradrenaline (NA)-turnover in the brain around birth and its significance for neonatal adaptation. NA and its metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) have been measured by high pressure liquid chromatography (HPLC) in the pons-medulla and cortex in rat foetuses and pups. The MHPG/NA ratio was used as an index of NA-turnover. Catecholamines were also determined in the adrenals for comparison. The MHPG/NA ratios were found to increase 2.7-fold in the pons-medulla and 2-fold in the cortex during the first day after birth. The surge of NA-turnover occurred after the pups had been breathing air for two hours. The increase of NA-turnover was significantly lower in the cortex of rat pups breathing a hypoxic gas mixture or when they were kept in a cooler environment. The differences were less marked in the pons-medulla. We conclude that breathing air stimulates NA-turnover in the brain of the newborn rat and this stimulatory effect is modulated by environmental factors. PMID- 1605044 TI - The effects of cortisol on insulin sensitivity in muscle. AB - The effects of cortisol on insulin sensitivity were examined in rats with the euglycaemic, hyperinsulinaemic clamp technique. Uptake of 2-deoxyglucose and incorporation of glucose into glycogen was followed in the white gastrocnemius, extensor digitorum longus, red gastrocnemius and soleus muscles as well as the liver (only glycogen synthesis). Maximal velocity and fractional velocity of the insulin-sensitive part of glycogen synthase (FV %) was measured in the muscles, as well as muscle fibre composition and capillary density. After 24 h exposure to cortisol, insulin sensitivity was diminished in the clamp measurements. This was paralleled by a decrease in glycogen synthesis in the most insulin-sensitive red gastrocnemius and Soleus muscles, but not in the white gastrocnemius or extensor digitorum longus muscles or the liver, and no effect was seen on 2-deoxyglucose uptake in muscles. FV % was markedly inhibited in all muscles. After 48 h exposure to cortisol, glycogen synthesis was markedly inhibited in all muscles, and 2-deoxyglucose uptake in all except the least insulin-sensitive muscle, WG. No changes in muscle morphology were found. These results suggest that the insulin resistance caused by cortisol is elicited in a stepwise manner, starting with an inhibition in the glycogen synthesis system in insulin-sensitive muscles, later including all muscles as well as 2-deoxyglucose uptake. This occurs without changes in morphology. PMID- 1605046 TI - The canine internal carotid system: regional differences in reactivity to nerve stimulation, noradrenaline and 5-hydroxytryptamine. AB - Reactivity of the canine internal carotid system to field electrical stimulation, noradrenaline and 5-hydroxytryptamine was determined isometrically using 4-mm cylindrical rings from the cervical and cavernous portions and middle cerebral artery. Electrical stimulation at supramaximal voltage (0.5-4 Hz, 0.2 ms duration) produced a frequency-dependent contraction that was similar in cervical and cavernous portions and lower in the middle cerebral artery. This response was blocked by tetrodotoxin (10(-6) M) or phentolamine (10(-6) M). Noradrenaline (10( 9) - 3 x 10(-4) M) produced concentration-dependent contractions and the sensitivity was: cervical portion = cavernous portion greater than middle cerebral artery, and this effect was blocked by phentolamine (10(-6) M). 5 hydroxytryptamine (10(-9) - 10(-5) M) caused concentration-dependent contractions and the sensitivity was: cervical portion less than cavernous portion less than middle cerebral artery. This response was depressed by lysergic acid diethylamide (10(-6) M). The results indicate that reactivity of the internal carotid system: (a) to alpha adrenergic activation by endogenous and exogenous noradrenaline is lower in the distal segment (middle cerebral artery) than in the proximal segments (cervical and cavernous internal carotid artery) and (b) to tryptaminergic activation increases as it courses toward the brain. Therefore, functional characteristics could be related to embryological origin which the segments of this vascular system are derived from. PMID- 1605047 TI - Effects of a postnatal exposure to cigarette smoke on hypothalamic catecholamine nerve terminal systems and on neuroendocrine function in the postnatal and adult male rat. Evidence for long-term modulation of anterior pituitary function. AB - The purpose of this paper was to study the possible long-term effects of postnatal exposure to cigarette smoke. Male Sprague-Dawley rats were exposed to the smoke from 2 cigarettes (Kentucky reference IR-1 type) every morning from day 1 after birth for a period of 5, 10 or 20 days. The rats were decapitated 24 hours (5, 10 and 20 days of exposure), 1 week (20 days of exposure) or 7 months (20 days of exposure) after the last exposure. Using the Falck-Hillarp methodology in combination with quantitative histofluorimetry catecholamine levels and changes in catecholamine utilization (alpha MT-induced CA fluorescence disappearance) in discrete hypothalamic catecholamine nerve terminal systems were analysed. Serum prolactin, LH, TSH and corticosterone levels were determined by means of radioimmunoassay procedures. In the postnatal period serum LH levels were significantly increased 24 hours after a 10 and 20 day exposure to cigarette smoke. In adult life after a 20-day postnatal exposure to cigarette smoke a highly significant increase was observed in serum prolactin levels, which were unaltered by this exposure when measured in the postnatal period. Twenty-four hours following a 20-day postnatal exposure, catecholamine utilization was increased in the medial palisade zone of the median eminence and substantially reduced in the parvocellular and magnocellular parts of the paraventricular hypothalamic nucleus. One week and 7 months following a 20-day postnatal exposure to cigarette smoke no alterations were observed in catecholamine levels or utilization in various hypothalamic areas including the median eminence. All the above changes were observed in the presence of an unaltered development of body weight. The results indicate that marked but temporary increases in LH secretion occur 24 hours after a postnatal exposure to cigarette smoke, while increase in prolactin secretion only develop in adult life, when the maturational processes of the brain and/or the anterior pituitary gland are completed. Changes in catecholamine levels and utilization are found in discrete hypothalamic nerve terminal networks but do not play a major role in mediating the above changes in anterior pituitary function and are probably the result of a withdrawal phenomenon. PMID- 1605049 TI - Overnight increases in haematocrit: additional evidence for a nocturnal fall in plasma volume. AB - Our previously published studies with monkeys describe a characteristic nocturnal haemodynamic pattern consisting of a monotonic decline in cardiac output and central venous pressure, and a concomitant rise in total peripheral resistance. These findings led us to hypothesize that there is a reduction in total plasma volume during the night. Since a fall in plasma volume should cause an increase in haemoglobin and plasma protein concentration, we designed this experiment to test the hypothesis that haematocrit levels would be significantly greater in the morning than in the evening. In a study of five monkeys, the levels of haematocrit were measured at 1700 h and at 0900 h the next morning for 14 days. The average morning haematocrit levels were 6.5% higher than the average evening values. Lower plasma volume and possibly greater blood viscosity could contribute to the pathophysiology of the morning increase in the incidence of 'silent' ischaemia and catastrophic vascular events such as sudden cardiac death, myocardial infarctions and strokes in man. PMID- 1605048 TI - Lactate transport during differentiation of skeletal muscle cells: evidence for a specific carrier in L6 myotubes. AB - Cellular uptake of lactate involves a carrier in numerous types of mammalian cells. In cultured rat L6 myoblasts, lactate diffuses freely. We show that during myogenesis a carrier appears at the myotube stage. The degree of cellular differentiation was determined by microscopic observation and by measurement of a marker of biochemical differentiation: the increase in specific activity of creatine kinases. PMID- 1605050 TI - Oxytocin increases and a specific oxytocin antagonist decreases pain threshold in male rats. PMID- 1605051 TI - Course of schizoaffective psychosis: further data from a retrospective study. AB - This study investigated the clinical course and outcome of 72 patients, diagnosed as suffering from schizoaffective psychosis (according to ICD-9 criteria) who also satisfied Research Diagnostic Criteria for schizoaffective disorder. The current overall functioning of these patients was related to the number and frequency of episodes, regardless of the duration of the illness: the lesser the number or frequency of relapses, the better the overall functioning. In addition, there were no statistically significant differences in psychosocial impairment between bipolar and unipolar schizoaffective disorder. PMID- 1605052 TI - AIDS and multiple sclerosis: neural and mental features. AB - The presence of mental disorder and cognitive functioning were examined in groups of 20 multiple sclerosis (MS) and homosexual acquired immunodeficiency syndrome (AIDS) ambulatory male outpatients matched for disability and demographic features. Patients who were somatically ill, had past central nervous system infection or tumours or abused intravenous drugs or alcohol were excluded. The groups significantly differed in mental symptoms and mental disorders (DSM-III classification) seen currently and after the diagnosis of MS or human immunodeficiency virus-1 infection. AIDS patients had pre-existing anxiety disorders that affected their current mental symptoms. MS patients showed more evidence of cognitive impairment than equally disabled AIDS patients. The differing neural and mental features are discussed in relation to the current concepts of subcortical and cortical disorders. PMID- 1605053 TI - Distress in the relatives of psychiatric patients admitted for the first time. AB - Seventy-three relatives of psychiatric patients aged 18-49 years admitted for the first time from a well-defined catchment area were interviewed using the Social Behaviour Assessment Schedule to determine the distress elicited by the patients' illness. The patients were interviewed with the Present State Examination, 10th edition, development version. Regardless of sex and age, frequency of contact and relation to the patient, the relatives experienced distress from symptoms, lowered social performance and the adverse effects of the illness. Informant's social class, male sex of patient and duration of illness significantly predicted distress. No differences were found in a comparison of the level of distress between non-organic psychotic disorders, mood disorders, anxiety disorders and psychoactive substance use disorders, but specific distressful areas within each disorder could be delineated. PMID- 1605054 TI - Biological correlates of the Newcastle Scale in depressive illness: a multivariate approach. AB - Rapid eye movement latency (RL), delta max thyroid-stimulating hormone (dmTSH) and 1600 (DST16) and 2300 (DST23) post-dexamethasone cortisol values were determined in a group of 93 depressed patients who were assessed with the Newcastle Endogenous Depression Diagnostic Index (NEDDI). After the effects of age, gender and severity of illness were controlled for, stepwise multiple regression showed that depressive psychomotor activity and weight loss were the 2 NEDDI items most contributing to explain DST23 variance, as was depressive psychomotor activity for dmTSH variance. When the depressive sample was dichotomized according to the presence of these 2 items, the 2 groups had significantly different DST16, DST23, dmTSH and RL values. This suggests that weight loss, agitation and retardation could represent a core feature of a biologically mediated depressive subtype. PMID- 1605055 TI - Cause of death in reactive psychosis. AB - Patients admitted for the first time with reactive psychosis have a greater mortality risk than the general population. This is caused by an increased risk of almost every cause of death, even cancer. However, the suicidal risk is increased considerably and suicide is the most frequent cause of death among men and women. Postpsychotic treatment that includes careful examination for somatic illness is recommended, and it is questioned whether the time has come to resolve reactive psychosis as a diagnostic term. PMID- 1605056 TI - Low thyroxine levels in female psychiatric inpatients with riboflavin deficiency: implications for folate-dependent methylation. AB - Intermediates in the folate-dependent methylation pathways may play a role in the etiology and treatment of such mental disorders as major depression. These pathways include a step dependent on a riboflavin (B2)-derived coenzyme, flavin adenine dinucleotide (FAD), which is reportedly sensitive to thyroid status and to phenothiazine and tricyclic drug exposure. In a sample of 52 male and female acute psychiatric inpatients, 17% (n = 9) showed B2 deficiency (i.e., insufficient FAD activity) on a functional red blood cell enzyme assay, but only one B2-deficient individual showed deficiency in another B-complex vitamin (folate). All patients with B2 deficiency were women, who were also significantly younger than the rest of the sample. The B2-deficient women had significantly lower thyroxine levels, even when controlling for sex and covarying for age. B2 deficient patients exhibited a nonsignificant trend toward more unipolar depression (44% vs 14%), but not toward bipolar or schizophrenic disorders. As in a previous study, drug exposure did not show a relationship to riboflavin deficiency in this sample. The findings suggest that B2 (FAD) activity may serve as a sensitive marker of thyroxine status in certain female psychiatric inpatients and that B2 deficiency may play an etiological role in defects of the methylation pathways in a subset of mentally ill individuals. PMID- 1605057 TI - Deliberate self-poisoning: treatment follow-up of repeaters and nonrepeaters. AB - Since 1986 psychiatrists and social workers of the Lund Suicide Research Center have investigated subjects admitted to the medical intensive care unit after a suicide attempt. Fifty-nine of 79 deliberate self-poisoners were interviewed 12 months after a suicide attempt. Twenty-one had previously been interviewed 6 months after the index suicide attempt. We obtained minor information on 8 subjects. Two patients had committed suicide. Sixteen subjects (27%) of those who were interviewed showed repeated suicidal behavior (repeaters) during the 1-year follow-up, and their psychiatric diagnoses at the index attempt were most commonly alcohol abuse and dysthymia (DSM-III, Axis I). Compared with nonrepeaters, repeaters had more often made previous suicide attempts, their index attempt was less serious and they were more often in psychiatric treatment at index. At follow-up, repeaters more often than nonrepeaters expressed the need for professional mental health support. Two-thirds of the patients were in treatment at follow-up. About half had remained in continuous treatment and most in psychiatric care for more than 1 year. Repeated self-poisoning occurred despite ongoing treatment. In view of the fact that numerous suicide attempters obviously remain in treatment for several years, we suggest further development and evaluation of long-term treatment strategies. PMID- 1605058 TI - Inappropriate vasopressin secretion in severe alcohol withdrawal. AB - Forty-one male alcoholics suffering from alcohol withdrawal syndrome were investigated to assess the relationship between vasopressin (ADH), water homeostasis and alcohol withdrawal. During 10 d, we found a significant decrease in serum vasopressin, from 3.08 +/- 0.61 to 1.71 +/- 0.22 pg/nl. There were no concomitant changes in osmolality, so that a general dysregulatory state of vasopressin secretion during alcohol withdrawal cannot be assumed. Only patients with delirium tremens (8/41) had higher vasopressin levels despite lowered serum osmolalities. These findings support the hypothesis of an inappropriate rebound secretion of vasopressin in severe alcohol withdrawal. Furthermore, they may contribute to the pathogenesis of focal alcoholic brain damage, because rapid and/or profound changes in osmolality are suspected to cause circumscribed cerebral demyelinization. PMID- 1605059 TI - The partners' views on precipitant stressors in suicide. AB - All suicides (n = 1397) in Finland during 1 year were studied by thorough interviews with the surviving next of kin. We included 388 suicides after which a spouse's or a cohabiting partner's subjective views of precipitant stressors in suicide process during the last 3 months and earlier in life were determined. In 82% of the cases the partner considered life events as precipitant stressors for the suicide. Among men, the most common stressors considered as suicide precipitants were somatic illness (25%), interpersonal discord (22%) and separation (14%). Among women these were mental disorder (28%), interpersonal discord (18%) and death of a significant other (17%). Somatic illness and retirement were more commonly considered as precipitants among older men, whereas interpersonal discord, separation and financial trouble were more common among younger men. Among women, job problems were more commonly considered as precipitants for younger subjects. Among both sexes, childhood adversity was more commonly reported among the younger subjects. PMID- 1605060 TI - Housing conditions and residential needs of psychiatric patients in Copenhagen. AB - A study of the extent of homelessness among 1581 psychiatric patients in Copenhagen found that 342 patients (22%) in contact with the psychiatric services had serious housing problems. A total of 112 (7%) were long-stay patients without a home address, 134 (8%) were in an unstable housing situation and 96 (6%) were actually homeless. The homeless among the psychiatric patients were characteristically single, on disability pension or general public assistance, most often under 45 years of age, often schizophrenic and, among the men, almost one third were alcohol abusers. The majority of the homeless preferred separate apartments, and the psychiatrists also considered this form of housing to be the most appropriate for them. Approximately one fifth were estimated to need staff supported housing, and the number of places in psychiatric group homes or halfway houses should therefore be increased. PMID- 1605061 TI - The interrater reliability of a Dutch version of the Structured Clinical Interview for DSM-III-R Personality Disorders. AB - This study presents data on the interrater reliability of a Dutch version of the Structured Clinical Interview for DSM-III-R Personality Disorders (SCID-II). Seventy outpatients were interviewed before the start of their treatment by one rater, while a second rater observed. Both raters were instructed to make independent ratings and the second rater was not allowed to participate in the discussion. On criterion level, interrater reliabilities appear to be very good, with a few exceptions (most reliabilities are higher than 0.75). However, all 5 observation criteria had poor interrater reliabilities. Agreement on personality disorder, on the whole, was excellent (overall kappa = 0.80). The possible reasons why relatively lower reliabilities are found with some criteria are discussed. Finally, problems encountered during the interviews are addressed and possible adjustments of the SCID-II are suggested. PMID- 1605062 TI - Manic-depressive psychosis in children younger than 15 years: a register-based investigation of 39 cases in Denmark. AB - Using a nationwide psychiatric case register covering a background population of 5.1 million inhabitants, 39 children (23 boys, 16 girls) were identified who got the diagnosis of manic-depressive psychosis between 1970 and 1986 before the age of 15. The frequency of manic-depressive psychosis in this child psychiatric population was 1.2%. The mean age for first-time admission with this diagnosis was 12.7 years. There was no sex difference. Twenty-six of the children got the diagnosis of manic-depressive psychosis during their first admission. Survival analysis was used to describe the prognosis and the diagnostic development of the group. As a whole, the group had a poor prognosis with many readmissions. The most common differential diagnoses were other types of psychosis in boys and oppositional and emotional disorders in girls. PMID- 1605063 TI - [Mesenteric ischemia in hemodialysis]. AB - Eighteen hemodialysis patients with the diagnosis of mesenteric ischemia (MI), admitted to the Renal Service in the last 5 years, were retrospectively reviewed. All patients, 10 males and 8 females, average age 66.3 +/- 8.6 years, were complaining of acute abdominal pain without other specific clinical or laboratorial findings, had their diagnosis confirmed during laparatomy, with ischemic involvement of the ileocecal/ascendant colon area in 14 cases and the small bowel in 4. Noteworthy was the high incidence of previous dialysis-induced hypotensive episodes (10/18), the presence of leukocytosis (13/18), the high average hemoglobin level of 9.4 gr/dl, and the constant finding of non-occlusive MI. Average time in-hospital was 15.4 days (2 to 30) and the mortality--88% (16 patients). The growing incidence of MI mostly of the non-occlusive type, and its grim prognosis, calls for an early diagnosis of functional ischemic colitis, and the adoption of preventive action to avoid bowel infarction. PMID- 1605064 TI - [Identification of a period of renal ischemic vulnerability studying the changes in the indicators of acute renal insufficiency after heart surgery with extracorporeal circulation]. AB - We studied the pre operative status and the 1st, 4th, 12th and 24th hours of the post operative period after open heart surgery with cardiopulmonary bypass with a crystalloid solution containing 10 gr of mannitol. We considered acute renal failure (ARF) as being any increase in plasma creatinine values of 0.25 mg/dl for the first 24 hours and 0.5 mg/dl for periods longer than 24 hours. Six patients had transitory ARF (28.5%). The maximum value of plasma creatinine was 2.3 mg/dl and no patients required renal function substitution. There were no deaths. We used as ischemia ARF indicators the urinary flow rate, urine/plasma creatinine ratio, urine/plasma osmolality ratio, sodium fractional excretion and free water reabsorption. We also measured the urinary N-A-Glucosaminidase (NAG). We found that creatinine clearance reached its lowest in the first and fourth hours. Beyond the fourth hour we observed, the urinary flow rate reduce significantly, the urine/plasma creatinine and osmolality ratios reach values traditionally associated prerenal ARF, an increase main free water reabsorption and a decrease in sodium fractional excretion with a close relationship between the less than 1 value and the increase in plasma creatinine. There was a significant NAG increase in the 24 th hour. The evidence of a vulnerability period for renal ischemic lesions between the 4 th and 12 th hour suggests a second mannitol administration during the first four hours of the post operative period. PMID- 1605065 TI - [Hemophiliacs with inhibitor. Experience at the Center of Medical Action for Hemophilia of the S. Jose Hospital]. AB - Factor VIII inhibitors arise in 5% to 15% of patients with hemophilia A in response to infusion to factor VIII concentrates and make the treatment of bleeding episodes extremely difficult. Various therapeutic approaches have been tried the decision depending on the type of haemorrhage, the antibody's titre and whether the patient has a low or high response. We report the clinical experience in 13 hemophiliacs with inhibitors to factor VIII. Prothrombin complex concentrates were administered with favorable effects in the most common haemorrhagic episodes, in the majority of patients. In two patients activated prothrombin complex concentrates were administered and in one case plasma exchange was made before high doses of factor VIII. These therapeutic approaches proved to be very effective in the control of hemostasis. PMID- 1605066 TI - [Spinal cord tumors. Anatomoclinical study]. AB - The authors review 36 cases of intramedullary spinal tumours, 17 ependymomas, 12 astrocytomas, 6 hemangioblastomas and 1 metastasis of leiomyosarcoma. The tumours were localized in the cervical region in 19 patients, in the thoracic region in 10 in the lumbar region in 4, and in the conus medullaris in 3. All patients presented a clinical picture of myelopathy. No differences were observed between the different hystological types. In 5 patients the tumour was associated with syringomyelia and one of these patients also presented a type I Chiari malformation. All patients were submitted to surgery (using microsurgical techniques in the last seven years). Radiation therapy was also given in 16 cases. Our results demonstrate that microsurgical resection is the only treatment that significantly improves the prognosis of these patients, from both the standpoint of the functional status and survival. PMID- 1605067 TI - [Unusual procedures used in reconstructive surgery and/or revascularization of the aorta]. AB - Since the advent of arterial surgery, four decades of development have evolved, characterized not only by a remarkable evolution of concepts, but also by the improvement of technics, means and methods utilized for arterial reconstructive surgery. This progress led to the promotion and improvement of the conventional surgical methods dedicated to the treatment of the most common aortic disorders, obstructive or aneurysmal. Endarterectomy, revascularization using synthetic bypasses or interposition of arterial prosthesis are the most common and standardized procedures which are used worldwide, giving gratifying and long lasting results, involving low or negligible risks. In clinical practice however one sometimes, faces rare conditions, poorly understood due to their rarity, in which the conventional methods may be regarded as inappropriate, unfit or even formally contraindicated. Some unusual or uncommon methods were devised to deal with such conditions, which are less popular due to their rarity, but may also be considered just as valid and reliable as conventional methods, bearing satisfactory and rewarding results. Among them we stress the bypass originated in the ascending aorta, the bypass from the descending thoracic aorta and the bypass arising from the supraceliac aorta. The main features of these procedures as well as the personal experience of their utilization obtained by the senior author constitute the essence of this presentation. PMID- 1605068 TI - [Surgical therapy of peptic stenosis of the esophagus in adults]. AB - One hundred and one patients with reflux esophagitis and strictures, submitted to different kinds of surgical solutions over the last 16 years, were revised. Seventy seven patients had dilatable stricture and the lower esophageal sphincter mechanism could be brought intra-abdominally in 70. In 36 there was radiographic evidence of hiatal hernia and 8 had a Barrett esophagus. The surgical technique employed in these cases was transgastric dilatation of the stricture, and Nissen fundoplication in 63 and partial fundoplication in 13 patients with peptic stricture post BI or BII6, gastroenterostomy or pyloromyotomy and vagotomy and post Heller myotomy. The post-operative mortality was 2.6% (2 in 77 patients) and morbidity 14.3%. Results after 5 years of follow-up have been classified as good to excellent in 88.3%. Six out of 9 remaining patients needed more than 3 dilatations in the first year after surgery and 3 of these were reoperated. Twenty four patients had a fixed stricture: In 22 of them, the area of esophagogastric stenosis was resected with replacement of the esophagus by colon interposition in 6, jejunum in 14, and a gastric tube with cervical anastomosis in 2. In two patients of advanced age and with respiratory problems a retrosternal by-pass with colon was performed. In this group the post-operative mortality was 12.5% (3 in 24 patients) and the morbidity 25%. The most common problems after one year of surgery were diarrhea (4 patients) and gastric fullness in 2. Eleven patients remained asymptomatic after 5 years (9 with jejunum interposition and 3 with colon) and 3 with jejunum were alive after 10 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605070 TI - [Spinal cord tumors]. PMID- 1605069 TI - [Oxygen free radicals and complications of diabetes mellitus]. PMID- 1605071 TI - [Ethics in health and research]. PMID- 1605072 TI - [Multiple myeloma. An unusual case]. AB - We describe the case of a 75 year old male patient, hospitalized because of sudden paraplegia. The radiological tests performed, revealed degenerative changes of the entire vertebral spine, osteolytic lesions of the seventh cervical and first two thoracic vertebrae, and lacunar lesions of the others. The erythrocyte sedimentation rate, total proteins and its electrophoretic study, as well as quantification of serum immunoglobulins were found to be normal. Regardless of these results, we continued our investigation in order to diagnose or exclude multiple myeloma (MM), which was confirmed by serum and urinary immunoelectrophoresis, that revealed monoclonal gammopathy IgG, K with low value of serum IgG and very high urinary values of Bence Jones K, and by the histological analysis of the necropsy material. In conclusion, we report a case where the probability of an alteration of the controlling immunological mechanisms must be considered. We suggest that there is a heavy chain suppression of the malignant clone, that would explain its very low value in peripheral blood. These findings associated to the absence of light chains in serum, have lead to a particular laboratorial expression of this myeloma. PMID- 1605073 TI - [Febrile coma and disseminated intravascular coagulation following heat stroke]. AB - A clinical case that occurred in a 42 years old female and which fulfils the diagnostic criteria for the entity described as Heat Stroke is presented. In this case, besides the usual manifestations of hyperpyrexia without sweating along with consciousness disorders, features of consumptive coagulopathy, rhabdomyolysis and well marked laboratory liver dysfunction have also been found. The severity of this situation and its less common occurrence in temperate climates, together with the uncertainty in establishing the diagnosis, namely when infection is suspected--in the present case the initial diagnosis was Sepsis, which led to patient's admission in an infectious diseases intensive care unit--motivate the authors to make this report. Furthermore, they consider this case to be a good example of the varied clinical and laboratory manifestations and possible severe complications that Heat Stroke may display. PMID- 1605074 TI - [Ethics of animal research and application to humans]. AB - Animal experimentation has proven to be of invaluable help in the understanding of biological functions, for the advancement of medical research and for the improvement of health conditions of both humans and animals. This phase of scientific progress is far from completed and there are no hints for substitution of all animal experiments by so called alternative methods. Therefore, there is a real need to analyse, without prejudice or undue dogmatic statements, the present situation in order to contribute to a responsible attitude, which should be transparent, understandable for lay people and useful as a background for the passing of adequate legislation. This process of analysis calls for the cooperation of scientists, a class which can neither be ignored nor treated as minor and should be above any suspicion of any part concerned. Finding a reasonable and just solution for the problem under debate can only result from the convergence of utilitarian and responsible ethical viewpoints. From utilitarian reasoning an overwhelming mass of evidence has resulted in favour of animal experimentation: medical progress would be severely maimed by prohibition or severe curtailing of animal experiments and catastrophic consequences would ensue. On the other hand, ethical considerations result in clear condemnation of useless or redundant experiments, of those causing disproportionate pain or suffering or of doubtful scientific standing: and to the recommendation that every effort should be undertaken in order to find and to establish on a sound scientific basis, alternative or complementary methods, i.e. those not involving animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605075 TI - [Ethics in researcher-research promotor relations]. AB - The performance of Clinical Trials can give rise to ethical problems especially between the researchers and the promotors but sometimes also with those who are in charge of the publication of results. Medicine and the Pharmaceutical Industry must face up to the need to try and save a marriage that is not only one of convenience but most of all lifesaving. The Industry supports the major slice of Postgraduate and Continuous Medical Education with its main goal being the promotion of its products. The Educational component we doctors are interested in is usually secondary for the Industry. A Clinical Trial comprises several steps beginning with the design of its protocol, its discussion by promotors and scientists and its performance where researchers, monitors, and official auditors have the main role. The analysis of the results should be handled by official boards unrelated to either promotors or researchers and their publication should be undertaken by a reliable Medical Journal whose editorial board would authenticate the accomplished scientific work. Ethical Commissions, both national and institutional, have a unique role in the analysis and authorization of Clinical Trials. Before any drug is put onto the pharmaceutical market, it is obligatory that the four successive phases of Clinical Pharmacological Studies be accomplished. A common problem we usually face is to differentiate a Phase IV from just a Promotional Trial. When a Promotional Trial is done, all the clinical goals of investigation have already been reached. The objectives of Promotional Trials are merely related to the Marketing Department and disregard any scientific purposes. Promotional Trials should not involve Universities, Hospitals and other official Institutions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605076 TI - Serum immunoglobulins in brain tumours. AB - Immunoglobulin level in the sera of 62 patients with intracranial space occupying lesions was assayed using the radial immunodiffusion method. Serum IgM levels showed a highly significant increase in all types of brain tumour when compared to controls. Serum IgG levels were also increased in benign as well as malignant cases. Serum IgA levels were high only in benign cases. Hence, increased serum Ig levels may be of prognostic value in these cases. PMID- 1605077 TI - Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage. AB - The aim of this study was to examine whether an increase in the serum concentrations of the two brain enzymes creatine kinase BB (CK-BB) and neuron specific enolase (NSE) can be demonstrated in patients with acute head injury and whether such an increase reflects release from damaged brain tissue. In 60 patients who had suffered minor to severe head injury, serial blood samples were drawn during the first hours after impact, and CK-BB and NSE were measured by radioimmunoassay. Computed tomography (CT) was also performed shortly after admission to hospital, and was repeated 1-3 days later in selected patients. Increased serum concentrations of both CK-BB and NSE were found in 88% of the patients with moderate to severe head injury (group 1, n = 18) and in 23% of the patients with minor head injury (group 2, n = 42), whereas CT showed contusion in only 41% and 2% of the group 1 and 2 patients, respectively. The following findings suggest that the enzymes had been released from brain tissue: 1) The maximum concentrations of CK-BB and NSE correlated with the severity of injury as assessed clinically and with the volume of contusion as estimated from CT (r = 0.79 with CK-BB, r = 0.72 with NSE). 2) The maximum concentrations of CK-BB and NSE were closely correlated (r = 0.87).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605078 TI - In vivo study of flow pattern at human carotid bifurcation with regard to aneurysm development. AB - In order to investigate the developmental mechanism of cerebral aneurysms, the in vivo flow pattern around human cervical carotid bifurcations was studied by flow visualization using digital subtraction angiography with an isotonic contrast medium. The blood stream containing the medium impinged on the apex, then proceeded along the walls of the branches. After opacification of the whole lumen around the apex, most of the medium was carried away, while some remained for a few seconds at the carotid sinus. In the internal carotid artery, the blood struck the wall at an oblique angle near the tops of the arterial curvatures. In cases with atheromatous plaque or kinking of the branch, the blood passed through the stenosed segment and moved upstream, indicating turbulence. The study suggests that haemodynamic forces around the apex consist mainly of impingement on the apex and shear stress to the wall at and around the apex. In branches, high shear stress seems to exist. It might be possible that high shear stress causes degenerative changes in the endothelial layer, initiating the formation of saccular and fusiform cerebral aneurysms. PMID- 1605079 TI - Haemodynamic, intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats. AB - Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure. A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies. PMID- 1605080 TI - Transclival approach to rabbit basilar artery for experimental induction of chronic vasospasm. AB - An experimental technique for producing delayed cerebral vasospasm in a rabbit model is described. The basilar artery is punctured via the transclival route and angiographic verification is illustrated. PMID- 1605081 TI - Autotransplantation of peripheral cholinergic neurons into the brains of Alzheimer model rats. AB - Current hypotheses regarding Alzheimer's disease implicate cholinergic function. In this study, peripheral cholinergic neurons in the vagal nodosal ganglion were transplanted into the brains of Alzheimer model rats. Eighteen Sprague-Dawley strain rats were divided into three groups: 1) unoperated control rats, 2) rats that had undergone bilateral destruction of the nucleus basalis of Meynert (NBM) (Alzheimer model), and 3) the transplantation group in which the vagal nodosal ganglion was transplanted into the cerebral neocortex one week after the bilateral destruction of the Meynert nucleus. Seven weeks after the transplantation rat behaviour was assessed using psychological tests (spontaneous activity, passive avoidance response and the Hebb-Williams maze test). The Alzheimer model rats had a statistically significant increase in spontaneous activity in comparison with controls (P less than 0.01). The transplant rats showed some amelioration of this abnormal increase in spontaneous activity observed in the Alzheimer model rats. All of the control rats showed conditioned passive avoidance responses, while only one Alzheimer model rat retained is shocked-conditions behaviour before 24 hours (P less than 0.01). Three of the six transplanted rats showed complete improvement in the passive avoidance response test. In the Hebb-Williams maze test, the rats with NMB lesions made more errors than the control rats. The transplanted rats had a lower number of errors than NBM-lesioned rats but still more than the controls. Histological examination revealed many cholinergic cells in the transplanted tissue, especially in the area adjacent to the cerebral cortical surface. The present results indicate that autotransplantation of peripheral cholinergic cells ameliorates abnormal behaviour in Alzheimer model rats. PMID- 1605082 TI - Delayed transplantation of foetal cerebral tissue into injured spinal cord of adult rats. AB - Delayed transplantation of foetal cerebral tissue into injured spinal cord of adult rats was performed for the purpose of evaluating the usefulness of the procedure for reconstructing the spinal cord and providing motor recovery. Transplanted tissue showed a survival rate greater than 80% and integration with the host tissue. Nerve fibers of the host surrounded the transplanted tissue, penetrating it. Foetal cerebral neurons matured into recipient spinal cord, but they were not organized in layers. The experience obtained suggests that delayed transplantation of foetal cerebral tissue into contused spinal cord is useful in morphological spinal cord reconstruction. Nevertheless, at least during the first two months after transplantation, clinical assessment of motor recovery showed no differences between transplanted and nontransplanted rats. PMID- 1605083 TI - Topography of the uncinate fascicle and adjacent temporal fiber tracts. AB - Neurosurgical procedures in the anterior temporal lobe are common, in which different postoperative neuropsychological deficits may occur. For the refinement of the surgical approach 10 human hemispheres were dissected using the method of dissection by Klinger, to gain more data about the fiber tracts in the anterior temporal lobe, respectively the temporal stem. The uncinate fascicle has a form like a curved dumb-bell with a thin (about 2 mm thick), fan-like arrangement of fibers in the frontal and temporal lobe. The solid portion runs in the extreme and external capsule through the limen insulae. The topography of adjacent important fiber tracts (inferior occipito-frontal fascicle, Meyer's loop, anterior commissure, inferior thalamic bundle) could be displayed. According to the results possible neuropsychological deficits and surgical considerations are discussed. PMID- 1605084 TI - Marking of the stereotactic target point by a radiopaque silicone sphere. Technical note. AB - We present a simple but efficient technique for marking the site of a stereotactic biopsy. This is done by a radiopaque Barium impregnated silicone sphere, which is introduced through the stereotactic cannula and placed at the target point. This allows a postoperative check of the target point by computer tomography or Magnetic Resonance Imaging and offers a landmark for further stereotactic intervention as well as for planning of high precision radiotherapy. Moreover it gives information about the growing direction of a tumour. The silicone spheres are well tolerated; no complications have occurred so far. PMID- 1605085 TI - CT-guided stereotactic biopsy aided by Doppler ultrasonic vascular monitoring. AB - The use of a 20 MHz pulsed Doppler technique during stereotactic brain tumour biopsies is described. By means of a miniaturized ultrasonic probe the tissue planned for biopsy was investigated for vessel signals. Out of 41 patients, with this technique a flow-pulse curve in front of the biopsy cannula was registered in 14 cases. In 9 cases one pulse curve was determined and in 5 cases two or more flow curves were found, indicating the presence of arterial vessels. The depth of the vessels signal could be localized and this area avoided for biopsy sampling. In a series of 41 stereotactic biopsies carried out in this way there was no intra-operative haemorrhage or postoperative haematoma. PMID- 1605086 TI - Cerebral salt wasting syndrome distinct from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). AB - Two cases with pituitary tumour developed postoperative hyponatraemia which was not caused by inappropriate secretion of antidiuretic hormone. The one case with non-functioning macro-adenoma showed severe hyponatraemia (116 mEq/l) on day 11 after trans-sphenoidal surgery in association with diabetes insipidus (DI). The patients was treated by aqueous pitressin and saline administration to control urinary output and keep positive salt balance at the same time. The other case with GH-producing macro-adenoma showed progressive negative sodium balance with the total loss of 644 mEq resulting in hyponatraemia of 133 mEq/l. This was corrected by additional salt intake. The plasma atrial natriuretic polypeptide (ANP), antidiuretic hormone (ADH) as well as aldosterone levels were normal in the latter case. These patients were considered to manifest primary salt wasting disorder, which should be clearly differentiated from the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). PMID- 1605087 TI - Problems related to dorsal root entry zone lesions. AB - Several clinical problems related to the dorsal root entry zone lesions (DREZLs) in 15 patients with chronic pain are presented and discussed in terms of ratings of pain relief following surgery, development of sensory or motor weakness and postmortem histologies. Subjective pain relief exceeding 70% was achieved at around 2 weeks after the operations in most patients (13/15), and then decreased in some to 30 from 70% in the follow-up observations. Our new "objective" pain relief score was tested in these patients. A significant positive correlation between subjective pain relief and our objective pain relief scale was found, but some discrepancies between them were also found during the follow-up. Sensory loss, motor weakness, paraesthesia and a new pain were found as complications in 12, 7, 4 and 6 patients, respectively. Postmortem histological findings of the spinal cord in two patients with systemic lupus erythematosus and uterine cancer, who received bilateral DREZLs twice and bilateral DREZLs plus commissural myelotomy, respectively, indicate that care should be taken to avoid extension of the coagulation beyond the dorsal horn. PMID- 1605088 TI - Cerebral vasospasm in elderly patients treated by early operation for ruptured intracranial aneurysms. AB - Cerebral vasospasm in elderly patients was studied under strict criteria. A total of 145 patients, who had been operated on in the acute stage after subarachnoid haemorrhage, were classified into two age groups. Those aged 59 years or younger were in group 1 (76 cases, 52%), and those aged 60 years or older were in group 2 (69 cases, 48%). The severities of both the subarachnoid haemorrhage on computed tomography scan and the angiographic vasospasm were graded from 0 to IV. Close correlations were found in both groups for the angiographic vasospasm grades to the incidences of both symptomatic vasospasm and low-density areas on computed tomography scan. Angiographic vasospasm was observed in 95% of group 1 and in 91% of group 2 patients. The incidences of permanent symptomatic vasospasm were 14% in group 1 and 19% in group 2. Low-density areas on computed tomography occurred in 16% of group 1 and in 17% of group 2. Generally, the higher the clinical grades and/or the higher the subarachnoid haemorrhage grades, the more severe were the vasospasms. These tendencies were more apparent in subarachnoid haemorrhage grading. The mortality rates were 8% in group 1 and 17% in group 2. However, when both the clinical grades and the subarachnoid haemorrhage grades were analyzed, there were no significant differences between groups 1 and 2 in either the severity of vasospasm or in the outcome. It must be concluded that neither the angiographic vasospasm grades nor the incidence of symptomatic vasospasm are significantly effected by age. PMID- 1605089 TI - The influence of concomitant intradural pathology on the presentation and outcome of patients with acute traumatic extradural haematoma. AB - The pre-operative and early postoperative CT scans of 120 patients who had surgery for acute extradural haematoma were reviewed, 88 cases (73%) had an extradural haematoma alone (Group 1) while 32 cases (27%) had an additional intradural abnormality (Group 2). The abnormalities were a subdural haematoma in eight, a haemorrhagic contusion in 16 and hemisphere swelling in eight. The two groups were compared with regard to the findings that an additional intradural abnormality is likely to be associated with an older age, an injury following a road traffic accident, a GCS less than 7 at operation, additional extracranial injuries and a poorer outcome. The increase in the percentage of patients who were unconscious from the onset and the decrease in those who were always conscious with a concomitant intradural damage was without statistical significance. PMID- 1605090 TI - The hyperaemic response to a transient reduction in cerebral perfusion pressure. A modelling study. AB - A mathematical model of cerebral blood flow and the cerebrospinal fluid circulation is described which permits the study of phenomena caused by dynamic changes in cerebrovascular autoregulatory or cerebrospinal fluid compensatory reserves. A transient decrease in cerebral perfusion pressure was produced by carotid artery compression. Comparison of the computer simulations with clinical and experimental data, reported elsewhere, suggests that the transient hyperaemic response (THR) is proportional to the strength of the autoregulatory response. The relationships between the magnitude and time course of the THR, and the period and level of reduction in CPP were studied. This model suggests that simple clinical tests based on the examination of THR using transcranial Doppler velocity measurements are of potential value for the non-invasive assessment of the autoregulatory reserve. PMID- 1605091 TI - Sex hormone binding and peritumoural oedema in meningiomas: is there a correlation? AB - Steroid receptor binding activity was evaluated in specimens of 28 human cerebral meningiomas using a dextran coated charcoal (DCC) assay. Oestrogen receptor (ER) binding activity at significant levels (greater than 10 fmol/mg protein) could be detected only in three postmenopausal females (11% positive cases) at low levels. Positive progesterone receptor (PR) binding was detected in eighteen of the twenty-eight analysed meningioma tissues (64% positive cases). A significantly higher level of PR in male than in female patients could be demonstrated. The degree of peritumoural oedema could be evaluated from CT scans. There was no significant correlation between lack and amount of peritumoural oedema and quantity of cytosolic PR binding activity. Therefore we conclude, that peritumoural oedema is related to other factors and a possible role of PR activity in development of peritumoural oedema and growth control of meningiomas could not be demonstrated. PMID- 1605092 TI - The enzymes from extreme thermophiles: bacterial sources, thermostabilities and industrial relevance. AB - This review on enzymes from extreme thermophiles (optimum growth temperature greater than 65 degrees C) concentrates on their characteristics, especially thermostabilities, and their commercial applicability. The enzymes are considered in general terms first, with comments on denaturation, stabilization and industrial processes. Discussion of the enzymes subsequently proceeds in order of their E.C. classification: oxidoreductases, transferases, hydrolases, lyases, isomerases and ligases. The ramifications of cloned enzymes from extreme thermophiles are also discussed. PMID- 1605093 TI - Biosynthesis of storage lipids in plant cell and embryo cultures. AB - The biosynthesis of storage lipids in plant cell and embryo cultures is discussed in the light of their significance in the breeding of agriculturally important oil seed crops. After a short introduction to the biosynthesis of storage lipids, i.e. triacylglycerols and wax esters, this review covers the occurrence and biosynthesis of storage lipids in plant cell and embryo cultures. Plant cells in culture generally contain low levels of both unusual fatty acids and triacylglycerols indicating that these cells are quite different from cells of oil storage tissues. There are a few exceptions to this rule which demonstrate that induction of genes involved in the expression of fatty acid modification and triacylglycerol assembly is possible in plant cell cultures. Such biosynthetically active plant cells may be of particular interest in future studies of storage lipid assembly. Both somatic and gametophytic embryos of oil plants exhibit high capacities for storage lipid biosynthesis and accumulation in vitro compared to cultured plant cells. Above all, the microspore-derived embryo system is recommended to both plant breeders and plant biochemists for the selection and multiplication of plants of superior quality. PMID- 1605094 TI - Improving the validity of the PSNI in assessing the performance of deaf parents of hearing children. AB - The content validity of the Parental Strengths and Needs Inventory (PSNI) for evaluating the child-rearing performance of deaf adults was assessed by replicating and extending an earlier cross-sectional descriptive study. Three types of subjects--deaf parents, hearing offspring, and hearing grandparents- provided the research data. The interview responses of 15 parent-child dyads were triangulated with grandparent questionnaire responses to identify parental issues not tapped by the closed-ended PSNI format. The content validity of the PSNI in its present form was found to be inadequate for assessing the strengths and needs of deaf parents. Recommendations for modifying the PSNI for use with deaf parents of hearing children are advanced. PMID- 1605095 TI - Reading comprehension test item difficulty as a function of cognitive processing variables. AB - This study reports the results of a componential analysis of items comprising Sections A and C of Form Z of the reading comprehension portions of the California Achievement Tests (CAT) (Tiegs & Clark, 1963). A set of problem components or attributes characterizing the test items in terms of manifest content, psychologically salient features, and processing demands was developed, including methods for their quantification. The contributions of these components to task difficulty were then evaluated using linear regression methodology. Item difficulty indices were transformations of the familiar proportion-correct item score, obtained from data gathered during the spring of 1989 from 158 deaf examinees. Variation in the item difficulty values was substantially accounted for in terms of a small number of predictor variables (R2 greater than or equal to .90). Implications of the results for construct validity and interpretation of test scores are discussed. PMID- 1605096 TI - Take longer steps faster, work more hours harder. PMID- 1605097 TI - Informing parents about educational options. How well are we doing? AB - This study explores an aspect of information delivery to parents by focusing on those who have chosen residential school placements for their children. Although most parents choose to send their deaf children to special programs in regular public schools, some do opt for residential school placements. Little is known about the foundations on which such decisions are made, and this study is a preliminary attempt to better understand parents' motives and expectations and to assess the adequacy of information provided to them. In 128 surveys from a sample of parents nationwide, a surprising number reported that they were not given information about placement options. Of those who were, many said they were dissatisfied with the information. A large proportion of the parents were satisfied with the residential school. The relationships among their reasons for this placement, their views of the advantages and disadvantages, and the information provided to them are discussed. PMID- 1605098 TI - Using the TOEFL at NTID/RIT. PMID- 1605099 TI - Interpreter's wrist. Repetitive stress injury and carpal tunnel syndrome in sign language interpreters. AB - Forty interpreters attending a regional Registry of Interpreters for the Deaf conference completed a questionnaire regarding symptoms related to repetitive stress injury (RSI), a generic classification of problems that occur after extensive, repetitive motion. RSIs, including the most prevalent form, Carpal Tunnel Syndrome (CTS), were surveyed. The vast majority (87.5%) of the interpreters in the sample reported that they had at sometime experienced at least two symptoms associated with RSI. Some (12.5%) who had CTS reported that they had been misdiagnosed. When asked how many other interpreters they knew with RSI problems, they reported, on average, that they knew more than four others. The data indicate that RSI is a severe problem among sign language interpreters and warrants immediate action. The term interpreter's wrist may best describe the malady. PMID- 1605100 TI - The influence of personal characteristics on rumor knowledge and transmission among the deaf. AB - Students who viewed themselves as members of the deaf culture listed all the current rumors they knew and the number of people to whom they typically transmit rumors. These two rumor variables, knowledge and transmission, were related to general anxiety level, extraversion, gender, self-reported preferred mode of communication, and type of high school attended. Congruent with previous research on hearing populations, deaf participants who were more anxious knew more rumors than did less anxious deaf participants. Results unique to the deaf population are also discussed. PMID- 1605101 TI - Roberto Francisco Pradez. Spain's first deaf teacher of the deaf. AB - This article examines developments surrounding the establishment of the school for the deaf in Madrid in the 19th century and the role played by Roberto Pradez, Spain's first deaf teacher of the deaf, during the school's first three decades of existence. Although he has been neglected historically, Pradez is a founding father of deaf education, a heroic figure who contributed crucially to the establishment and operation of Spain's first state-sponsored school. This study underscores the need to reexamine the historical record to recover Spanish deaf history. PMID- 1605102 TI - Vision problems among students in schools and programs for deaf children. A survey of teachers of deaf students. AB - Vision problems are more common among deaf people than among the general population. Eight percent of the students in schools and programs for deaf children can be expected to have vision problems. We sent questionnaires to institutions and programs for deaf children, requesting information about the extent of vision problems among their students and about their teachers' levels of preparation in the area of vision impairment. Responses were received from 490 teachers. The data confirm that significant numbers of deaf students also have vision problems, and that teachers do not receive adequate training and information to meet the needs of this population. PMID- 1605103 TI - Are we ready for PL 99-457? AB - Public Law 99-457 has renewed interest in providing preschool education for hearing-impaired children. It is not clear, however, whether we're ready for this mandate to expand services to an ever-younger population and its families. This study presents a "snapshot" of the trends in preschool programs and of the availability of programming to students in various parts of the country. We obtained lists of programs from a sample of state level special education offices, and then sent the programs detailed questionnaires. The returned surveys provided a snapshot of the instructional approaches used in many preschool programs and indicated that there may still be some problems in the availability of preschool programming and in the ability of programs to uniformly provide the sorts of quality comprehensive services mandated by the law. PMID- 1605104 TI - Warren A. Cook. An industrial hygiene pioneer. 1900-1992. PMID- 1605105 TI - Warehouse workers' headache: carbon monoxide poisoning from propane-fueled forklifts. PMID- 1605106 TI - Adsorption characteristics of organic solvent vapor on activated carbon under fluctuating vapor concentrations. AB - Air containing organic solvent vapor was introduced into a glass column packed with activated carbon particles under the conditions of rectangularly fluctuating vapor concentration. All the experiments were started from an adsorption cycle and were succeeded by a nonadsorption cycle. These cycles were repeated at the same intervals under a constant flow rate. The experimental breakthrough curves and the breakthrough times were compared with those obtained under a constant vapor concentration. The breakthrough curves at the fluctuating vapor concentration were oscillated and the breakthrough times were sometimes significantly shorter than those at the constant vapor concentration when the designed average vapor concentration, i.e., the concentration averaged over an equal number of on and off cycles, was equal. This tendency was greater for the solvents that have higher saturated vapor pressures, such as acetone, methyl acetate, and methyl chloroform, especially when the fluctuating time interval was long. Because the vapor concentrations in the work environments are fluctuating, the effective time of charcoal tubes and respirator cartridges may become shorter than the expected values, which are based on the constant vapor concentration laboratory studies. PMID- 1605107 TI - Permeation resistance of glove materials to agricultural pesticides. AB - The toxicities of many agricultural pesticides require that hand protection be used by persons who mix, load, and apply these products, as specified on the label and material safety data sheet. Selection of gloves for formulations that contain organic solvents is particularly problematic because a solvent that permeates the glove can carry with it the active ingredient of the pesticide formulation. With a test method that measures the simultaneous permeation of the carrier solvent(s) and active ingredient(s), in particular those active ingredients that have low solubility in water and low volatility, over 100 permeation tests (in triplicate) with approximately 20 pesticide formulations were conducted with 13 different glove materials. These results are summarized and generalizations are presented within the perspective of the large base of permeation data for neat chemicals and another large permeation study with pesticides. Key among the findings is that the carrier solvent generally permeates first and at a much higher rate than the active ingredient. Furthermore, the permeation behavior of formulations containing solvents generally mirrored that of neat carrier solvents alone. Thus, insight into the selection of the most appropriate glove material for a given pesticide formulation can be gained from permeation data for neat chemicals. For the types of solvents that may be present in pesticide formulations, preferred materials include nitrile rubber, butyl rubber, and plastic film laminates. Natural rubber and polyvinyl chloride materials generally are not recommended. PMID- 1605108 TI - Exposure to dust, endotoxins, and fungi in the animal feed industry. AB - In the Dutch animal feed industry, approximately 6000 workers are exposed to organic dust, originating mainly from raw materials such as grain, pulses (peas and beans), and waste products from the vegetable oil and starch industries. In this study, 79 stationary dust samples and 530 personal dust samples from eight animal feed production facilities were analyzed. The stationary total dust samples showed gravimetric concentrations ranging from 0.2 to 25 mg/m3 (geometric mean [GM] 1.3 mg/m3). Concentrations of smaller particle fractions (respirable, thoracic, and inspirable dust) were considerably lower. Personal inspirable dust concentrations were considerably higher than stationary concentrations and were strongly related to job titles. Pooled personal inspirable dust concentrations ranged from 0.2 to 450 mg/m3 (GM = 2.4 mg/m3). After adjusting for differences between inspirable and total dust, 25% of the measurements exceeded the Dutch maximum allowed concentration (MAC) for total nuisance dust (10 mg/m3) and 42% exceeded the American Conference of Governmental Industrial Hygienists' threshold limit value for grain dust (4 mg/m3). Endotoxin concentrations ranged from 0.2 to 1870 ng/m3 inspirable dust (GM = 5.1 ng/m3). Endotoxin appeared to be less prevalent in respirable dust than in larger dust fractions. Concentrations in dust appeared to be related to stages in the production process. Colony-forming units (cfu) of fungi ranged from 130 to 15,300 cfu/m3 (GM = 2300 cfu/m3) and were in parallel measurements more strongly related to endotoxin concentrations than to dust concentrations. Clearly, workers in the Dutch animal feed industry are frequently exposed to dust levels above recommended Dutch and American levels. Exposure levels to endotoxin and to fungi are quantified.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605109 TI - Use of physiologically based pharmacokinetic models to establish biological exposure indexes. AB - This paper presents a simulation modeling approach to establish biological exposure indexes (BEIs) from ambient occupational exposure limits (OELs). A physiologically based pharmacokinetic (PB-PK) model was used to describe the disposition of volatile organic chemicals in the human. The model was used to simulate an exposure regimen similar to a typical work schedule. Exposure concentrations were set to equal the ambient OELs of the corresponding chemicals. Chemical concentrations in the expired air and blood and concentrations of metabolites in the urine were estimated with the PB-PK model for this exposure condition. Because the OELs establish the criteria for ambient exposure to chemicals, the concentrations of chemicals or their metabolites in biological media resulting from exposure to the OELs would likewise define acceptable exposure standards. On the basis of this rationale and method, BEIs were developed for 13 common industrial organic chemicals. PMID- 1605110 TI - Health effects of tank cleaners. AB - A total of 29 tank cleaners and 31 referent controls participated in the study. In most cases, the tank cleaners were employed in small companies, usually specialized subcontractors such as firms only working in refineries cleaning oil tanks and handling oil spills. The air concentrations of hydrocarbons (HCs) in tanks containing residuals from heavy fuel oil were generally low, unless the oil was still warm. Addition of light fuel oil to facilitate the cleaning of tanks containing viscous, heavy fuel oils resulted in total airborne HC levels of 1000 1500 mg/m3. High levels of HC were measured in tanks with low-boiling petroleum fractions (naphtha and light fuel oils) of 1000-2600 mg/m3 (maximum). Today, most cleaners use air-supplied respirators or air-purifying respirator cartridges inside tanks with petroleum products or other chemicals. The exception is small firms handling fuel oils for heating purposes where only 50% of the workers use protective equipment regularly; the other workers only occasionally use protective equipment even if the air concentrations of HC are high. Protective equipment is rarely used in small, domestic tanks. Measurements of heart rate showed that tank cleaning is, at times, a highly strenuous job. No differences between tank cleaners and controls were found with respect to spirometry, liver enzymes, or frequency of micronuclei. Acute intoxications were not frequently reported in this group. However, this investigation may underestimate the true risk, as it is a cross-sectional study that found that exposures were highly variable, both quantitatively and qualitatively. In many cases, the tank cleaners knew very little about the potential hazards or the proper use of protective equipment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605111 TI - The use of tracer gases to determine dust dispersion patterns and ventilation parameters in a mineral processing plant. AB - A study was conducted in a fluorspar milling plant to assess the effectiveness of tracer gases as a reliable supplement to conventional air-monitoring and ventilation measurements. In the course of this study, a tracer gas was used as a surrogate substance to analyze the direction and the rate of spread of contaminants from various potential dust production points in the plant. Time weighted average and continuous mineral dust concentrations were measured in several areas of the plant; these results were compared and correlated with steady-state tracer gas concentrations in the mill. Time-weighted average dust concentrations varied between 0.18 and 0.57 mg/m3 for total dust and 0.04 and 0.20 mg/m3 for quartz respirable dust, depending on the location. Correlation of these values with steady-state tracer gas concentrations yielded linear relationships with correlation coefficients (R2) of 0.95 and 0.87, respectively, for total and quartz dust. Results from this study, therefore, indicate that tracer gases may help model the spread of airborne respirable dust from point sources. These tracer gas releases also allowed the simultaneous quantitative determination of air residence times and contaminant clearance times from the building. Hence, tracer gases will help industrial hygienists obtain useful data with respect to building ventilation. PMID- 1605112 TI - 1990 Henry F. Smyth, Jr. Award Lecture. Criteria for occupational exposure limits by selected countries. PMID- 1605113 TI - Cause and control: education and training of professional industrial hygienists for 2020. AB - By the year 2020, the environmental movement will have established a recognized profession, expert at studying deleterious effects in the working and public domains. Environmental science practitioners will be better able to identify and relate ill effects to the presence of adverse agents in the environment; they will not, however, necessarily be skilled at developing systems for control. Industrial hygienists should provide the unique and special skills required to establish economically optimum control systems. Industrial hygiene should by then have been redefined to emphasize this critical role of its professional members. A new orientation for education is therefore proposed to provide a sound basis for the professional needs of industrial hygienists who should be at the peak of their careers in 2020. Members of the profession should then be the leaders in research on, and practice of, the science and engineering of design, installation, and monitoring of control systems for occupational and environmental hazards. The preferred educational background for entry to the profession should be some branch of engineering, which by then must have recovered its lost status and be divided into fewer specialized compartments than it is today. Engineering should provide a broader base for students entering professional education in this field, who will be more concerned with prevention and engineering control of both occupational and environmental hazards, rather than with measurement and epidemiology of the biological and toxicologic sciences. Preparation for professional work in industrial hygiene will call for the specialized education of engineers required to design and maintain processes that minimize the use, production, or generation of hazardous substances.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605114 TI - Process safety management: resources from the American Institute of Chemical Engineers for use by industrial hygienists. AB - Industrial hygienists often work closely with engineers to control occupational safety and health hazards. This working relationship involves an educational process in which both engineers and industrial hygienists learn from one another. The Center for Chemical Process Safety (CCPS) of the American Institute of Chemical Engineers (AIChE) is expanding the opportunity for interdisciplinary cooperation and education by producing a series of guidelines publications on the technical and scientific issues critical to preventing and mitigating major releases of toxic materials. Examples of these guidelines include Hazard Evaluation Procedures; Technical Management of Chemical Process Safety; Chemical Process Quantitative Risk Analysis; and Safe Storage and Handling of Highly Toxic Hazardous Materials. Additional topics are addressed in the 8 guidelines in print and the 15 others in preparation. Several guidelines contain specific examples that illustrate how industrial hygienists, engineers, and other readers can use the guidelines to help address chemical process safety problems. Another CCPS activity involves an effort to include an awareness of health, safety, and loss prevention as an integral part of undergraduate chemical engineering education. For practicing engineers and industrial hygienists, a number of continuing education courses on topics such as process hazard analysis, process risk assessment, and process safety are offered by the AIChE. All of these resources are particularly timely in light of the Occupational Safety and Health Administration's recently enacted rule on Process Safety Management of Highly Hazardous Chemicals. PMID- 1605116 TI - Three-dimensional echocardiography: techniques and applications. AB - Current echocardiographic devices provide only 2-dimensional views of the heart. To appreciate 3-dimensional structural relations, therefore, requires mental reconstruction of 2-dimensional views by an experienced observer. Our ability to answer new questions about the heart could be increased if 2-dimensional images could be combined to display 3-dimensional relations. Such 3-dimensional reconstruction would permit analysis of structures of unknown or complex shape and the noninvasive quantification of cardiac chamber size and function without making geometric assumptions. To overcome previous limitations, mechanisms have been developed for automated integration of images and positional data during routine echocardiographic scanning, thereby greatly enhancing the efficiency and application of image reconstruction. Refining the diagnosis of mitral valve prolapse has presented a uniquely 3-dimensional problem requiring information previously unavailable from the 2-dimensional technique. To date, 3-dimensional studies have demonstrated that the mitral valve is saddle-shaped in systole, so that apparent superior leaflet displacement in the mediolateral 4-chamber view, often seen in otherwise normal individuals, lies entirely within the bounds defined by the mitral annulus and occurs without leaflet distortion or actual displacement above the entire mitral valve. Other applications of 3-dimensional image reconstruction include calculation of ventricular volume and ejection fraction by transthoracic or transesophageal scanning without geometric assumptions; improving the standardization and accuracy of 2-dimensional measurements by improving spatial appreciation; and 3-dimensional reconstruction of vascular walls to guide interventions. In the future, systems for acquiring multiple views more rapidly by parallel processing and improving endocardial border extraction should allow more routine application of 3-dimensional methods as the next stage in the evolution of cardiac ultrasound, thereby expanding the range of questions that can be answered. Achieving these goals will depend, in large measure, on persistence in developing the necessary technology. PMID- 1605115 TI - Quantitative ultrasonic imaging: tissue characterization and instantaneous quantification of cardiac function. AB - Quantitative myocardial tissue characterization is being developed to complement and expand conventional echocardiography by delineating the physical state of myocardium under diverse pathophysiologic conditions. Real-time quantitative integrated backscatter imaging has already been applied to patients with ischemic heart disease, hypertrophic cardiomyopathy, and cardiac allograft rejection in clinical investigations performed in the United States, Europe, and Japan. A recently introduced modification of imaging processing algorithms employed for characterization of tissue facilitates automatic detection of endocardial-blood interfaces and on-line quantification of ventricular size and function. Further progress and anticipated developments in quantitative ultrasonic imaging will undoubtedly augment the clinical applications of tissue characterizations based on myocardial integrated backscatter for improved diagnosis, elucidation of pathophysiology, and assessment of cardiac function. PMID- 1605117 TI - Intravascular ultrasound of the coronary arteries: current applications and future directions. AB - Although angiography is widely applied in the diagnosis of the coronary artery disease (CAD), studies have questioned the accuracy of radiographic methods. Miniaturized intravascular ultrasound devices offer several potential advantages, including a tomographic orientation and the ability to characterize atherosclerotic plaques. Two dissimilar technical approaches to transducer design have emerged: mechanically rotated devices and multi-element arrays, each yielding small coronary catheters (1.1-1.8 mm in diameter). Initial studies of coronary ultrasound have demonstrated few serious untoward effects. In most normal subjects, the vessel wall is laminar in appearance with an intimal leading edge and subintimal sonolucent layer averaging less than or equal to 0.20 mm in thickness. In most CAD patients, the thickness of the leading-edge or sonolucent zone is abnormally increased. Atherosclerotic abnormalities are frequently evident in segments with no angiographic lesion. At sites with a circular lumen shape, minimum diameter by ultrasound and angiography correlate closely, r = 0.93. At sites with an eccentric lumen, significant disagreement between angiography and ultrasound diameter is evident, r = 0.78. Correlation between angiography and ultrasound from percent stenosis is moderate, r = 0.63. Following balloon angioplasty percutaneous transluminal coronary angioplasty (PTCA), morphologic findings include complex cracks, splits, and dissections, and minimum lumen diameter by angiography and intravascular ultrasound correlate poorly. Recent advances have improved the utility of coronary ultrasound, including smaller catheters and a device combining a miniature imaging transducer (1.16 mm) with a low profile balloon (0.028-0.033 inch). Important current limitations include inability to visualize the smallest coronaries and tight stensoses. The future of coronary ultrasound is promising, propelled by the unique capability of this modality to image atherosclerotic plaques directly. PMID- 1605118 TI - Future developments in cardiac ultrasound: possibilities and challenges. PMID- 1605119 TI - Myocardial perfusion: contrast echocardiography perspectives. AB - Contrast echocardiography may become a useful means of quantifying transmural regional myocardial perfusion patterns, experimentally and clinically, in a variety of settings. Contrast echocardiography has already been used in the operating room to study perfusion during coronary artery bypass graft (CABG) surgery. Other recent studies have demonstrated the ability of contrast echocardiography to predict wall motion improvement following acute myocardial infarction and therapeutic intervention. This is significant in the light of the discrepancy that has recently been shown between epicardial coronary vessel diameter and coronary flow. Studies suggest that both tissue and blood flow and volume may be quantitatively evaluated using contrast echocardiography, and these parameters ultimately may be used to assess tissue viability or vascular reserve. Contrast echocardiography techniques have been shown to be safe and reliable, and provide a high degree of spatial and temporal resolution. PMID- 1605120 TI - Sonicated serum albumin in contrast echocardiography: improved segmental wall motion depiction and implications for stress echocardiography. AB - We undertook to study the ability of intravenously administered sonicated albumin microbubbles to opacify the left ventricular (LV) cavity, enhance endocardial delineation, and thereby improve the interpreter's confidence in evaluating regional wall motion in patients whose baseline echocardiograms were believed to be technically difficult because of limited endocardial resolution. We studied 30 adult patients with endocardial border dropout of greater than or equal to 20% on routine echocardiography. Efficacy was evaluated by the investigator and 2 blinded observers using an opacification grading system of 0 (no appearance in LV cavity) to 3+ (full LV chamber opacification). Effective opacification was indicated by a score of greater than or equal to 2+. Border delineation improvement equaled a change from grade A (not well delineated) to grade B, C, or D (well delineated) of at least 1 of 6 LV wall segments. Initially all patients received a 0.08 mL/kg injection. The patient received 2 additional injections of 0.14 and 0.08 mL/kg given 5 minutes apart if the initial volume produced at least 2+ LV opacification. Otherwise, a final injection of 0.22 mL/kg was given. In all cases, the patients' arms were raised after injection to enhance venous passage. When graded by the investigator, 29 patients (97%) exhibited greater than or equal to 2+ opacification. When graded by the blinded observers, 27 patients (90%) exhibited greater than or equal to 2+ opacification. Improved border delineation was noted by the investigator in 90% of patients, and the blinded observers noted improvement in 97% (excluding 1 patient who, if scored by a blinded observer, would have received a higher dose of contrast agents).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605121 TI - Clinical applications of myocardial contrast echocardiography. AB - Myocardial contrast echocardiography is a new technique that uses microbubbles of air in conjunction with simultaneously performed 2-dimensional echocardiographic imaging. Currently, it can be used to determine myocardial perfusion in the cardiac catheterization laboratory and the operating room. For myocardial contrast echocardiography to find a broader clinical application for the assessment of myocardial perfusion, it will be necessary to opacify the myocardium from venous injection of contrast in humans. In this regard, enhancement in bubble engineering, optimization of echocardiographic systems (greater sensitivity and dynamic range), and availability of digital image enhancement techniques will be required for myocardial contrast echocardiography to realize its full clinical potential by the year 2000. PMID- 1605122 TI - Intravascular ultrasound and intracardiac echocardiography: concepts for the future. AB - Intravascular ultrasound imaging is a catheter-based method that has been shown to be better than contrast angiography in the detailed assessment of coronary and peripheral arterial atherosclerotic lesions, arterial dissections and clots, aortic and pulmonary arterial disorders, and the effects and complications of interventional therapy in various vascular beds. Evaluation of refined ultrasound catheters, combined imaging and therapeutic devices, and off-line 3-dimensional reconstruction capabilities indicates that intravascular ultrasound could provide guidance during various catheter-based therapeutic procedures. Early experience with intracardiac echocardiography suggests that this technique could evolve as a clinically useful method with diagnostic, monitoring, and guidance applications. Future directions for further development include designing of miniaturized imaging devices, "look-forward" imaging devices, low frequency devices for whole heart imaging, multifrequency ultrasound catheters and multifunction ultrasound consoles, and approaches to real-time 3-dimensional imaging, on-line tissue characterization, automated acoustic quantification and tissue characterization, the study of myocardial perfusion, and catheter-based acoustic myocardial biopsy. These developments could lead to the conversion of catheterization laboratories into integrated imaging, monitoring, and therapeutic stations. In addition, continuous monitoring of cardiac function could be possible in the critical care unit and in the operating room as well. Ongoing advances in catheter technology and image processing indicate that these concepts are within the realm of becoming reality. PMID- 1605123 TI - Transesophageal echocardiography: state-of-the art and future directions. AB - Transesophageal echocardiography complements transthoracic examination in 5-10% of patients referred to the echocardiographic laboratory. Clinical indications for performing this procedure are continually evolving. The semi-invasive nature of this procedure necessitates that it be judiciously used and that trained personnel undertake the procedure. Complications of the procedure need to be kept in mind. Future directions in the development of this technology involve newer, multiplanar, multifrequency transducers, digital archiving and retrieval, wide field imaging, and 3-dimensional reconstruction. For the present, transthoracic echocardiography must remain the primary echocardiographic window imaging the heart, with defined clinical applications for transesophageal echocardiography. PMID- 1605124 TI - Exercise echocardiography. AB - Exercise echocardiography is a versatile, noninvasive diagnostic test that involves the recording and interpretation of 2-dimensional echocardiograms prior to, during, and after exercise. By analyzing and comparing wall motion at each stage, a prediction about the presence or absence of coronary artery disease can be made. The development of a wall motion abnormality is both sensitive and specific for the presence of a significant coronary stenosis. Changes in regional systolic function during exercise enable the clinician to distinguish between infarction and ischemia. Thus, the test yields information on the presence, extent, severity, and location of coronary artery disease. Echocardiography can be adapted to almost any form of stress, although treadmill or bicycle exercise are most commonly employed. An advantage of bicycle stress echocardiography is the opportunity to image during exercise, rather than relying on postexercise recording. This contributes to enhanced sensitivity, although false-positive results may increase due to the difficulties of analyzing wall motion during strenuous exercise. Exercise echocardiography increases the diagnostic accuracy of stress testing in a manner similar to radionuclide perfusion imaging. It is particularly useful in the setting of an ambiguous stress electrocardiography (ECG) or when a false-negative or false-positive result is suspected. It has been successfully applied to patients following revascularization and yields useful prognostic data in a variety of clinical situations. Exercise echocardiography is being increasingly utilized as a safe and accurate test in patients with known or suspected coronary artery disease. PMID- 1605125 TI - Dobutamine stress echocardiography. AB - Two-dimensional echocardiography is a versatile, accurate, and readily available method for the assessment of cardiac anatomy and function, and extensive experience has been gained in the analysis of left ventricular wall motion. Using modern imaging techniques, regional as well as global wall motion analysis can be performed. Echocardiography can be used in conjunction with a protocol for either exercise or pharmacologic cardiovascular stress in order to identify the distribution and severity of coronary artery disease, with the induction of a regional wall motion abnormality being a sign of myocardial ischemia. The use of dobutamine infusion to accomplish stress echocardiography is a safe, accurate, and practical method for the diagnosis of coronary artery disease in patients unable to exercise. In addition to the evaluation of inducible ischemia, preliminary work is being performed with dobutamine stress echocardiography for the assessment of risk and patient prognosis following acute myocardial infarction and as an indication of tissue viability for myocardium that remains dysfunctional at rest following thrombolytic therapy. PMID- 1605126 TI - The impact of Chinese medicine on America. PMID- 1605127 TI - Predictive value of subjective and objective evaluation before acupuncture treatment. AB - To evaluate if it is possible to predict the outcome of acupuncture treatment in patients with knee osteoarthrosis, six treatments were given during a 3 week period. Follow-up time was 9-17 weeks. Seven parameters were evaluated to examine if they had any influence on the outcome of treatment: Age, duration of disease, pain, range of knee movement, analgesic consumption, knee score (an objective and subjective evaluation of the knees) and x-ray changes. Twenty-nine patients were included with a total of 42 osteoarthritic knees waiting for a total knee replacement. The median age was 69.2 years, and median duration of disease was 4.2 years. 85% of the participants reported a subjective effect, and in 88% an objective effect was found. Although there were some significant differences when you looked at the 7 parameters above, the pattern was not a consistent one. Follow up results also indicated that those with the best immediate results, not necessarily were the ones with the best long-term effect. It is not possible to predict the outcome of acupuncture treatment of osteoarthritic knees. Immediate results are not a guide-line for long-term results, which indicate that acupuncture research must include a follow-up period. PMID- 1605128 TI - Electron microscopical and immunohistochemical studies on the induction of "Qi" employing needling manipulation. AB - During a sparrow-pecking and twisting-needle manipulation to the acupoints BL 23, 24 and 25 for an induction of "Qi", it was found that some transparent materials were binding to the needles after removed from the volunteer's skin. Electron microscopical analysis of the transparent materials revealed that they corresponded to the injured fascia made up of collagen fibers, elastic fibers, fibroblasts, adipocytes and mast cells. Rarely were nerve fiber-like structures observed in the materials. Immunohistochemically, calcitonin gene-related peptide positive nerve fibers could be demonstrated in the acupoint BL 24 associated fascia. A possible functional relationship between the needle manipulation and the induction of Qi-sensation is discussed along with the acupoint tissue constitution. PMID- 1605129 TI - Studies on folk medicine "thang-kau-tin" from Taiwan. (I). The anti-inflammatory and liver-protective effect. AB - Five species of crude drugs are used as "Thang-kau-tin" on Taiwan market: (1) the stem of Mallotus repandus (Willd.) Muell.-Arg, (2) the stem and root of M. repandus (Willd.) Muell.-Arg, (3) the stem of Bauhinia championii Benth, (4) the stem with hooks of Uncaria hirsuta Haviland and (5) the stem with hooks of U. rhynchophylla Miquel. To clarify the effect of these crude drugs as anti inflammatory and liver-protective agents, studies were conducted on water extracts of these five crude drugs. The statistical analysis (ANOVA) indicated that the stem of M. repandus showed the best anti-inflammatory activity against the paw edema induced by carrageenan. Nevertheless, the acute increase of GOT and GPT levels caused by CCl4 were markedly decreased by the treatment of M. repandus (stem), B. championii and U. hirsuta as a recipe group. The pathological changes around the central vein including fatty change, ballooning degeneration, cell necrosis, the increase in lymphocytes and Kupffer cells were improved by the treatment with the group of crude drugs as mentioned above. PMID- 1605130 TI - Development of natural crude drug resources from Taiwan (X). Pharmacognostical studies on the Chinese crude drug "han-lian-cao". AB - In a previous paper(1), it was reported that the drug "Han-lian-cao", in Taiwan was derived from the entire plant or aerial part of Eclipta prostrata L. and Alternanthera sessilis R. Brown. In this paper, the histological studies of "Han lian-cao" derived from Wedelia and Hypericum plants, and of 3 species of Wedelia related plants distributed in Taiwan were made. The results showed that it was possible to classify these species by their external and internal characteristics. In addition, a key to the characteristics of the whole plants of Eclipta, Alternanthera, Wedelia and Hypericum plants are hereby given. PMID- 1605131 TI - Effects of tokishakuyakusan, keishibukuryogan and unkeito on DNA polymerase alpha activity in uteri of pregnant mare's serum gonadotropin-treated immature rats. AB - To provide some insights how herbal medicines affect deoxyribonucleic acid (DNA) synthesis in the uterus, the DNA polymerase activities (alpha and beta) in uterine samples taken from rats were measured. DNA polymerase alpha activity with respect to DNA content revealed alpha cyclic change with the highest level on proestrus, while DNA polymerase beta activity showed no significant changes during the estrous cycle. The increased period of the activity coincided with that of 17 beta-estradiol (E2) but not progesterone (P4) in the blood. Injection of 10 IU pregnant mare serum gonadotropin (PMS) on day 27 of age gradually increased DNA polymerase alpha activity in uteri, while concomitant treatment with PMS and 200 micrograms Tokishakuyakusan (TS), Keishibukuryogan (KB) or Unkeito (UT) suppressed the enzyme activity, with a most remarkable effect of KB. These results suggest that TS, KB or UT suppresses in vivo DNA polymerase alpha activity induced by PMS in the rat uterus. PMID- 1605132 TI - Effects of "kyushin", a drug containing toad venom, on experimental congestive heart failure in rabbits. AB - Effects of "Kyushin" (KY-2), a drug containing toad venom, on a low-output-type heart failure model produced in rabbits by protease treatment on the left ventricular anterior wall, were examined. Heart rate, aortic blood flow (AoF), left ventricular systolic pressure (LVP) and maximal rate of rise of LVP (max dP/dt) in this model were maintained at lower levels than those in normal rabbits, while left ventricular end-diastolic pressure (LVEDP) and systemic vascular resistance (SVR) were maintained at higher levels, and the mean blood pressure (MBP) was at a normal level. KY-2 was administered intraduodenally to the animal. KY-2 improved heart failure state by increasing the AoF, LVP and max dP/dt, and by decreasing the LVEDP and SVR without a significant change in MBP. These results suggest that the beneficial effects of KY-2 on this heart failure model originate from their cardiotonic activity. PMID- 1605133 TI - Life events and depression: the plot thickens. AB - Explored increasingly complex models of the stress-depression relationship. Many contemporary studies of depression have largely neglected environmental factors, including stressors. The author's research initially incorporated stress into cognitive models of depression and demonstrated individual vulnerability to specific types of stressors. Then research on the family transmission of depression showed that family and child stressors are important but commonly neglected predictors of children's high risk for depression as offspring of depressed mothers. Recently, emphasizing the context in which depression occurs, we have shown that people contribute to the occurrence of stressors and have been exploring the predictors of stress generation. At each step, the stress depression model grows more complex. PMID- 1605134 TI - Social support and victims of crime: matching event, support, and outcome. AB - Investigated the buffering properties of six types of social support (three perceived, three received) with regard to four psychological consequences (depression, anxiety, fear of crime, hostility) of criminal victimization (violent crime, property crime). These relationships were examined using longitudinal data collected from a sample composed of representative subsamples of victims and nonvictims. Effects of the perceived support measures (perceived appraisal support, perceived tangible support, self-esteem) were more pervasive than those of the received support measures (received informational support, received tangible support, received emotional support). Perceived support consistently exhibited buffering effects, protecting both violent and property crime victims against various symptoms they would have otherwise experienced. The stress-buffering capabilities of received support were limited to informational and tangible help protecting victims of violence from experiencing excessive fear. These findings are discussed in the context of recent theoretical developments concerning the stress-support matching hypothesis. PMID- 1605135 TI - Confounding as a problem in relating life events to health status in elderly individuals. AB - Explored two types of confounding relevant to research relating major life events to physical illness in elderly individuals: (a) contamination of life events lists by health-related and subjective items; and (b) failure to control for illness existing prior to the life event assessment period. Community-residing elderly individuals (M = 70.4 years) completed two measures of health status in each of two waves of testing. During the second wave, participants also completed a life events list. Independent judges categorized the life events as health related or not and further categorized non-health-related events as subjective or objective. Results indicated that life events-illness correlations were influenced by the presence of confounded items and that when illness present prior to the life event assessment period was controlled the relationship between confounded life events and illness decreased. These results underscore the importance of assessing possible sources of confounding when conducting life event illness research with elderly individuals. PMID- 1605136 TI - Groups as social network members: overlooked sources of social support. AB - In a study of the link between physical disability and social relationships among the elderly, questions about social network and social support evoked a surprisingly large number of group responses. People mentioned "my grandchildren," "the people in my building," "people at the senior center," and other groups in ways that suggested that the real unit of support was extraindividual and could not be accurately understood by reference to individual people within those groups. This paper describes the frequency of such responses and the circumstances under which they emerged. Definitions of social support and of social network should not be restricted to dyadic relationships between individuals; better understanding of social support processes would derive from consideration of the kinds of social support functions best offered by groups vs. individuals and consideration of differences in the ways in which support is derived from groups and individuals. PMID- 1605137 TI - Haemophilus influenzae and viruses 100 years later: from influenza to human immunodeficiency virus. PMID- 1605139 TI - Uses and misuses of oxygen in hospitalized patients. AB - PURPOSE: To document the use/misuse of oxygen therapy as compared with antibiotics in internal medicine inpatients. To determine whether the same care was being taken in the prescription and administration of both forms of therapy. PATIENTS: Ninety-six eligible patients at a university teaching hospital were entered into a study examining the use of oxygen. They were compared with 60 patients for whom antibiotics were prescribed. MATERIAL AND METHODS: Three hundred thirty consecutive newly admitted patients were screened for the presence of either (1) oxygen apparatus at the bedside, (2) physician orders for oxygen, or (3) oxygen orders noted in nursing kardex. Those meeting one of these three criteria were observed on up to four occasions over 48 hours following study entry. Similarly, patients were screened for medical orders or nursing medication kardex notation for antibiotics and were also observed for proper prescription and administration of medication. Procedural errors, determined by kardex audit and direct patient observation, were compared for the individuals with specific oxygen orders and those receiving antibiotics. RESULTS: Oxygen delivery apparatus was found in the room in 17 of 96 patients without it ever having been ordered by the physician or noted in the nursing kardex. In 27 of 96 patients, oxygen was noted in the nursing kardex and administered to patients without a physician order. There were no cases of antibiotic therapy without a physician order. Observations of 47 patients with specific orders for oxygen revealed the following errors: (1) physician order incorrectly transcribed to nursing kardex (16%), (2) flow meter off (34%), (3) oxygen delivery apparatus improperly worn (57%), (4) wrong fractional inspired oxygen concentration (58%). Improper transcription of antibiotic orders occurred on only one occasion (2%), and antibiotics were improperly administered in 5%. Arterial blood gas determinations preceded oxygen orders in 61%, whereas microbiologic cultures preceded antibiotic orders in 87% of the patients. CONCLUSIONS: We conclude that oxygen therapy is neither prescribed nor administered with the same attention that is given to other drugs such as antibiotics. Oxygen prescription and/or delivery is associated with significantly greater error than that seen with antibiotics. Education of medical personnel should stress more prudent prescription and use of oxygen in hospitalized patients. PMID- 1605138 TI - Haemophilus influenzae type b bacteremia in adults with AIDS and at risk for AIDS. AB - PURPOSE: Our objective was to determine the number of cases of Haemophilus influenzae type b bacteremia in patients with and at risk for acquired immunodeficiency syndrome (AIDS) from January 1983 to June 1991 at a municipal hospital in Bronx, New York. PATIENTS AND METHODS: We reviewed blood culture records of adult patients admitted to North Central Bronx Hospital from January 1983 to June 1991 to identify cases of bacteremic H. influenzae type b disease. The hospital charts and admission chest radiographs of bacteremic patients were then reviewed. RESULTS: Ten of 15 cases of adult H. influenzae type b bacteremia occurred in patients with AIDS or who were at risk for AIDS. Seven had AIDS at presentation. Nine were active or former intravenous drug users (IVDUs). All 10 cases were associated with a respiratory source, and five of the 10 patients also had H. influenzae type b isolated from sputum. All H. influenzae type b strains were negative for beta-lactamase. CONCLUSIONS: Human immunodeficiency virus positive IVDUs may be at increased risk for bacteremic H. influenzae type b infections. Empiric antibiotic regimens for community-acquired pneumonia in these patients should include appropriate antibiotics for the treatment of H. influenzae type b. In addition, these patients may be candidates for conjugate H. influenzae type b vaccine trials. PMID- 1605141 TI - Admission stool guaiac test: use and impact on patient management. AB - PURPOSE: A stool guaiac test is often performed on newly hospitalized patients as part of the admission evaluation. However, little is known regarding the value of testing stool obtained by digital rectal examination. We sought to document the use of the admission stool guaiac test in a teaching hospital, to determine its diagnostic yield, and to assess its potential benefit to patients. MATERIALS AND METHODS: We performed a retrospective review of the medical records for 264 consecutive patients admitted to internal medicine services during a single month, of whom 202 received a stool guaiac test on admission. Information was collected on the frequency of guaiac testing, indications for testing, test results, and diagnoses established. RESULTS: Criteria were established to distinguish "clinically indicated" from "routine" use of the admission stool guaiac test. Indicated tests were positive more often than routinely performed tests (35% versus 11%, p less than 0.001). Most patients with positive tests received further testing for gastrointestinal disease, whether or not the test was indicated. Of 104 patients with indications, 25 were ultimately found to have gastrointestinal lesions, most of which were clinically important. Of 98 patients tested routinely, only four had diagnoses established, of whom three had benign conditions. Four of five patients with cancer had clinical indications for testing. The fifth was diagnosed only after he experienced gross rectal bleeding several days after admission. CONCLUSIONS: Like other commonly applied diagnostic tests, the stool guaiac test obtained during the admission physical examination is best reserved for patients whose clinical presentation provides a reason for testing. In patients without clinical indications, the test is of uncertain value and only infrequently leads to important diagnoses. PMID- 1605140 TI - Treatment of adults with severe aplastic anemia: primary therapy with antithymocyte globulin (ATG) and rescue of ATG failures with bone marrow transplantation. AB - PURPOSE: To evaluate a policy of immunosuppression with antithymocyte globulin (ATG) as primary therapy for adults with severe aplastic anemia (SAA) regardless of the availability of an HLA-identical bone marrow donor. PATIENTS AND METHODS: Thirty-one consecutive adults with SAA who satisfied the age criteria for allogeneic bone marrow transplantation (BMT) (age less than 51 years) were treated with ATG 20 mg/kg/day for 10 days along with high-dose corticosteroids. Patients with an HLA-identical donor received a transplant if they did not respond to ATG or if they developed life-threatening complications during or soon after ATG administration. Eight patients with no response to ATG were also treated with oral cyclosporine 12.5 mg/kg/day. RESULTS: Eleven patients had a complete and five a partial response to ATG; two patients improved with cyclosporine treatment, resulting in an overall response rate of 58% to immunosuppression. Nine of 14 patients with donors received a BMT: seven because they did not respond to ATG and two because of serious infections. Seven grafts were obtained from related and two from unrelated donors. There was no significant difference in survival between those with and without a related HLA identical donor (log-rank p value = 0.969). At a median follow-up of 58 months, 26 of 31 are alive with an actuarial survival of 80% at 5 years. Two patients died of infection, two died from complications of BMT, and one remains transfusion-dependent. One patient died of refractory leukemia at 30 months; one patient relapsed with hypoplasia 95 months after initial therapy with ATG. He showed a complete response to treatment with cyclosporine. No other late hematologic events have occurred. CONCLUSIONS: This treatment approach resulted in the restoration of hematopoiesis and independence from transfusion in 80% of patients with SAA entered into the study. The efficacy of allogeneic BMT in salvaging cases in which ATG failed does not appear to be compromised. Follow-up for the development of clonal hematologic disorders remains an important part of this treatment policy. PMID- 1605142 TI - Management and epidemiologic analyses of an outbreak due to methicillin-resistant Staphylococcus aureus. AB - PURPOSE: Following implementation of special measures to control a nosocomial outbreak of methicillin-resistant Staphylococcus aureus (MRSA), we used immunoblot typing in conjunction with antimicrobial susceptibility testing to investigate the epidemiology of this event and to determine whether this outbreak represented the failure of infection control measures to limit the spread of previously endemic MRSA strains or the introduction of a new strain of MRSA. MATERIALS AND METHODS: Isolates of MRSA recovered from hospitalized patients were initially categorized on the basis of antimicrobial susceptibility results. Organisms susceptible to ciprofloxacin and/or trimethoprim/sulfamethoxazole were recovered from patients at a relatively constant rate prior to December 1988 and were categorized as endemic isolates. Subsequently, there was an outbreak due to organisms resistant to both of these antibiotics; these were therefore categorized as outbreak isolates. Isolates were later characterized by immunoblot typing. Prior to this analysis, isolates were given code numbers so that clinical and epidemiologic data as well as resistance patterns were not known until this testing was complete. RESULTS: Between January 1986 and November 1988, an average of 3.9 patients per month acquired nosocomial MRSA in the Sepulveda Veterans Administration Medical Center. In contrast, from December 1988 to October 1989, 369 MRSA isolates were collected from 125 patients (an average of 11.4 patients per month). Prior to December 1988, all tested nosocomial isolates of MRSA were susceptible to ciprofloxacin and/or to trimethoprim/sulfamethoxazole. In contrast, the outbreak was due to spread of MRSA isolates resistant to these antibiotics. Immunoblot typing of 204 isolates from 98 individuals identified five distinct immunoblot types of which types B and C were by far the most common. Type B was highly associated with outbreak isolates, whereas type C was associated with endemic isolates (p less than 0.001). All sequential isolates from single patients that belonged to different susceptibility categories demonstrated discordant immunoblot types. In contrast, concordant immunoblot types were observed for 25 of 27 sequential isolates that displayed minor variations in antimicrobial resistance. The institution of more stringent infection control measures was followed by the return of nosocomial MRSA acquisition rates to pre-outbreak levels. Although novobiocin and trimethoprim/sulfamethoxazole were extensively used to treat patients harboring outbreak and endemic isolates, respectively, in no instance was the initial MRSA isolate from any patient resistant to novobiocin and only 6% of initial endemic isolates displayed trimethoprim/sulfamethoxazole resistance. A modest, significant increase in the resistance of endemic isolates to various other antimicrobial agents was noted however. CONCLUSION: Immunoblot analyses provided strong, corroborative evidence that at least two separate strains of MRSA were present during the outbreak and that a newly introduced strain with a distinctive antimicrobial resistance pattern was primarily responsible for the rapid spread of MRSA during the outbreak. The observation that previously effective infection control measures failed to prevent the nosocomial spread of a newly introduced community-acquired MRSA strain suggests that a single set of control measures may not be equally efficacious against all strains of MRSA. In this regard, previously reported variations in resistance to topical antimicrobials and/or antiseptics, and differences in virulence factors such as colonization potential, invasiveness, and survival on fomites, may warrant further study. Control of the outbreak strain of MRSA in our institution did occur after the implementation of more strenuous isolation procedures.(ABSTRACT TRUNCATED) PMID- 1605143 TI - Prognostic implications of a negative dipyridamole-thallium scan: results in 360 patients. AB - PATIENTS AND METHODS: A total of 360 patients with either normal perfusion (314) or fixed defects (46) on dipyridamole-thallium scans were followed over an average period of 16 months. Of the 360 patients, 194 subsequently underwent major noncardiac surgery. RESULTS: There were a total of eight cardiac events including two postoperative complications (one fatal and one nonfatal myocardial infarction) and six cardiac events during long-term follow-up (one sudden death and five nonfatal infarctions). During the follow-up period, three patients underwent coronary artery bypass surgery. The low cardiac event rate could not be explained by a low pretest likelihood of coronary artery disease: 77% of the 360 patients had either typical angina pectoris, a previous myocardial infarction, or peripheral vascular disease, which is associated with a high prevalence of coronary artery disease. CONCLUSIONS: In patients with a high pretest likelihood of coronary artery disease, the absence of thallium redistribution on a dipyridamole-thallium scan denotes a very low (1%) cardiac risk for major noncardiac surgery as well as low long-term cardiac mortality (0.3%) and morbidity (1.4%) rates. The coronary death rate is comparable to that of patients with minimal (less than 50%) coronary stenoses. PMID- 1605144 TI - The natural history of isolated left ventricular diastolic dysfunction. AB - STUDY OBJECTIVE: To assess the natural history of isolated left ventricular diastolic dysfunction. PATIENTS AND METHODS: Follow-up (average duration, 68 months) was obtained in 51 patients with isolated left ventricular diastolic dysfunction at cardiac catheterization, characterized by (1) an elevated left ventricular end-diastolic pressure; (2) normal left ventricular end-diastolic and end-systolic volumes; (3) normal left ventricular ejection fraction; (4) no coronary artery disease; and (5) no valvular disease. RESULTS: During follow-up, seven patients died, but only one died of cardiac causes. Of the 44 living subjects, 20 (45%) noted new-onset symptoms of congestive heart failure, with 11 (25%) of these requiring hospitalization, and 12 (27%) required hospitalization for recurrent chest pain. CONCLUSIONS: Isolated left ventricular diastolic dysfunction is associated with a low cardiac mortality; at the same time, however, it is associated with substantial morbidity. PMID- 1605145 TI - Spectrum of subclinical and overt hypothyroidism: effect on thyrotropin, prolactin, and thyroid reserve, and metabolic impact on peripheral target tissues. AB - PURPOSE: Subclinical hypothyroidism is found in about 7.5% of females and in about 3% of males. It appears to be a risk factor for atherosclerosis and for coronary heart disease and can affect various other target organs. The morbidity and clinical significance of subclinical hypothyroidism are controversial. Therefore, we evaluated the metabolic impact of progressive thyroid failure in patients with various degrees of hypothyroidism compared with control subjects. PATIENTS AND METHODS: We investigated 86 female patients with the whole spectrum of subclinical hypothyroidism (n = 69) and of overt hypothyroidism (n = 17) and 52 euthyroid women as controls. All subjects underwent full medical and endocrine evaluations (including measurements of thyrotropin [TSH], TSH beta- and alpha subunits, and prolactin before and after oral administration of thyrotropin releasing hormone [TRH]) as well as lipid profiles and different tests of peripheral thyroid hormone action. All hypothyroid patients were divided into five categories according to disease severity: grades I to III (subclinical hypothyroidism, with normal thyroxine [T4] levels) and grades IV and V (overt hypothyroidism, with diminished T4). RESULTS: In grade I subclinical hypothyroidism (basal TSH below 6 mU/L), we found significant changes in the clinical index (p less than 0.05), apoprotein A-I level (p less than 0.05), and stimulated prolactin level after oral TRH (p less than 0.001). The findings were similar in grade II (TSH 6 to 12 mU/L). Further changes could be demonstrated in grade III (TSH above 12 mU/L) with a definite elevation of ankle reflex time (p less than 0.001), serum myoglobin level (p less than 0.01), and, to a lesser extent, creatine kinase (p greater than 0.1). The mean low-density lipoprotein cholesterol (LDL-C) level showed an increase of 18%, which was not significant because of marked individual variations (p = 0.15). The frequency of elevated LDL C levels was definitely higher in patients with grade III disease compared with the controls (42.9% versus 11.4%, p less than 0.05) and with patients with grades I and II disease. Total cholesterol, triglycerides, apoprotein B, and the systolic time intervals (pre-ejection period, corrected for heart rate [PEPc]) were clearly elevated only in overt hypothyroidism (grades IV and V) (p less than 0.01). CONCLUSION: Subclinical hypothyroidism has significant effects on some peripheral target organs at an early stage (grades I and II), but affects LDL-C, skeletal muscle, and myocardial contractility only at a later stage (grades III, IV, and V). Our data of elevated LDL-C in grade III subclinical hypothyroidism provide a likely pathophysiologic explanation for the reported association of coronary heart disease with this syndrome. The impact of increased prolactin secretion, observed in subclinical hypothyroidism, on gonadal function and infertility has yet to be clarified. Therapy with thyroxine should be recommended in at least some patients with subclinical hypothyroidism. Patients with high TSH levels (above 12 mU/L) will require treatment because of the metabolic effects on several target organs. Before treatment is advocated in all patients with subclinical hypothyroidism, the benefits and long-term side effects of thyroid hormone therapy should be clarified by prospective studies in larger groups of patients. PMID- 1605146 TI - Wilson's disease: current status. AB - OBJECTIVE: To review current concepts about the pathogenesis, clinical manifestations, and treatment of Wilson's disease, with an emphasis on recent developments. DATA IDENTIFICATION: Published information was identified using MEDLINE and through extensive manual searching of bibliographies in identified sources. RESULTS: The basic biochemical alteration responsible for deranged hepatobiliary copper homeostasis in Wilson's disease has yet to be identified. The gene for Wilson's disease has been mapped to chromosome 13, but the function of its gene product has not yet been determined. The clinical manifestations of Wilson's disease are varied and often nonspecific and include a range of hepatic, neurologic, and psychiatric findings. Penicillamine remains the drug of choice for the treatment of Wilson's disease, but recent experience suggests that trientine and zinc may be safe, effective alternatives. All three drugs are probably safe for use in pregnant patients with Wilson's disease. Liver transplantation is the only effective treatment for Wilsonian fulminant hepatic failure and corrects the underlying metabolic defect. CONCLUSIONS: Wilson's disease is a disorder of hepatobiliary copper excretion manifested predominantly by hepatic and neurologic copper toxicosis and inherited in an autosomal recessive pattern. Although the specific underlying biochemical defect remains to be defined, specific therapy is available and usually successful. Maintaining a high index of suspicion is critical in diagnosing this readily treatable inherited disease. PMID- 1605147 TI - Adenosine and the treatment of supraventricular tachycardia. AB - Adenosine has recently become widely available for the treatment of paroxysmal supraventricular tachycardia. In order to evaluate its role in the management of arrhythmias, we have reviewed the literature on the cellular mechanisms, metabolism, potential for adverse effects, and clinical experience of the efficacy and safety of intravenous adenosine. Adenosine produces transient atrioventricular nodal block when injected as an intravenous bolus. This is of therapeutic value in the conversion to sinus rhythm of the majority of paroxysmal supraventricular tachycardias, which involve the atrioventricular node in a re entrant circuit. The mean success rate was 93% from over 600 reported episodes. Compared with other antiarrhythmic agents, adenosine is remarkable for its rapid metabolism and brevity of action, with a half-life of a few seconds. It commonly produces subjective symptoms, particularly chest discomfort, dyspnea, and flushing, which are of short duration only. No serious adverse effect has been reported. Arrhythmias may recur within minutes in a minority of patients. Comparative studies have shown that adenosine is as effective as verapamil in the treatment of supraventricular tachycardia, and has less potential for adverse effects. Patients with supraventricular tachycardia should initially be treated using vagotonic physical maneuvers. Immediate electrical cardioversion is indicated if the arrhythmia is associated with hemodynamic collapse. Adenosine is the preferred drug in those patients in whom verapamil has failed or may cause adverse effects, such as those with heart failure or wide-complex tachycardia. The safety profile of adenosine suggests that it should be the drug of first choice for the treatment of supraventricular tachycardia, but only limited comparative data to support this view are available at present. PMID- 1605148 TI - Prophylactic use of the intra-aortic balloon pump in high-risk cardiac patients undergoing noncardiac surgery: a decision analytic view. AB - OBJECTIVE: As the indications for the intra-aortic balloon pump (IABP) continue to evolve, a potential new use may be the prophylactic preoperative insertion of the IABP in the high-risk cardiac patient undergoing noncardiac surgery. Our objective is to present a general approach to the high-risk cardiac patient who may benefit from the prophylactic insertion of the IABP. DESIGN: Case reports and a decision analysis. METHODS: A decision model was constructed that weighs the risk of life-threatening postoperative complications against the risk of vascular complications, including surgery and possible amputation, from IABP insertion. RESULTS AND CONCLUSIONS: A review of the literature identified 10 patients who underwent IABP placement prior to noncardiac surgery. These patients, along with our three cases, define a population of patients for whom the prophylactic IABP may be useful. This population includes patients with coronary artery disease (CAD) for whom bypass grafting is not an option due to: (1) inoperable CAD; (2) a severe coexisting disease process (such as a malignancy); or (3) the emergent nature of the noncardiac procedure. The decision analysis suggests that patients whose preoperative assessment places them at very high risk for postoperative complications (Goldman class IV or Detsky class III undergoing major surgery) may benefit the most from prophylactic placement of an IABP prior to noncardiac surgery. PMID- 1605149 TI - AIDS and the conundrum of Job. PMID- 1605150 TI - Reactive hypoglycemic coma due to insulin autoimmune syndrome: case report and literature review. AB - Recurrent episodes of postprandial hypoglycemic symptoms culminated in hypoglycemic coma in a hypertensive but otherwise healthy man while he was taking hydralazine. The patient was found to have an extreme elevation in the immunoreactive insulin level, leading to the discovery of insulin antibodies in the absence of prior exposure to exogenous insulin. Negative results of an anatomic study of the pancreas and an inability to reproduce hypoglycemia during a prolonged fast helped to exclude insulinoma. In contrast, symptomatic hypoglycemia developed in response to oral glucose loading and was associated with an elevation in total and free insulin as well as C-peptide levels. The patient was diagnosed with insulin autoimmune syndrome, which, although a common source of hypoglycemia in Japan, has been well documented in only 15 cases from other countries. HLA typing revealed the patient to be positive for groups Cw4 and DR4, a combination that has been preliminarily associated with insulin autoimmune syndrome in Japan. Unlike the majority of cases previously reported, this patient had no clinical or serologic evidence of an underlying autoimmune disorder and had not been exposed to drugs containing sulfhydryl groups. This case adds to the world literature on insulin autoimmune syndrome, lends support to a postulated HLA association, and documents the presence of insulin autoantibodies in the absence of another underlying autoimmune disorder. PMID- 1605151 TI - Optic neuropathy and central nervous system disease associated with primary Sjogren's syndrome. AB - Three cases of optic neuropathy associated with primary Sjogren's syndrome are reported. All three patients had clinical manifestations of primary Sjogren's syndrome, although two of the patients did not report sicca symptoms at initial examination. Two patients had focal neurologic signs in addition to optic neuropathy. The differentiation of this syndrome of optic neuropathy, focal neurologic signs, and Sjogren's syndrome from multiple sclerosis and antiphospholipid antibody syndrome is important for reasons of treatment and prognosis. This diagnostic differentiation was facilitated by positive tests for xerophthalmia and findings of positive minor salivary gland biopsy. High titers of antinuclear antibody, anti-SSA(Ro), and anti-SSB(La), and the absence of antiphospholipid antibodies provided additional help in the differential diagnosis. In 5 years of observation, none of the patients developed symptoms of multiple sclerosis or additional connective tissue disorders. PMID- 1605152 TI - Chronic inflammatory arthritis after treatment with high-dose interleukin-2 for malignancy. AB - Interleukin-2 (IL-2) immunotherapy resulted in the development of inflammatory arthritis in three male patients with metastatic cancer. Two patients developed a clinical picture consistent with rheumatoid arthritis. A third patient with a remote history of Reiter's syndrome developed a recrudescence of an inflammatory arthritis after treatment with IL-2. The clinical, laboratory, and histologic data on the patients and the potential pathophysiologic mechanisms are discussed. PMID- 1605153 TI - Transient neurologic deficit caused by chronic subdural hematoma. AB - Transient neurologic deficits are an unusual presentation of chronic subdural hematoma. Presented herein are three patients with transient aphasia and right sided sensory-motor abnormalities caused by subdural hematoma. Review of the literature revealed 32 cases similar to ours. Presenting complaints were aphasia (77%), sensory symptoms (57%), headache (48%), hemiparesis (50%), and visual disturbance (3%). Fifteen patients underwent cerebral angiography; only three showed significant carotid atherosclerosis. Electroencephalograms were performed in seven patients; five revealed lateralized slowing, but none showed epileptiform activity. Drainage of the hematoma was uniformly curative, although six patients had transient postoperative symptoms. Patients presenting with transient deficits require imaging to rule out the presence of a chronic subdural hematoma. PMID- 1605154 TI - Tracheal obstruction secondary to extravasation of intravenous fluids from a central catheter port. PMID- 1605155 TI - Digital vasculitis associated with interferon therapy. PMID- 1605156 TI - Recovery of visual function in anterior ischemic optic neuropathy due to giant cell arteritis. PMID- 1605157 TI - Treatment of cytophagic panniculitis with cyclosporin A. PMID- 1605158 TI - Simultaneous onset of systemic sclerosis (scleroderma) and lung cancer: a case report and histologic analysis of fibrogenic peptides. PMID- 1605159 TI - Risk factors for stroke in nonrheumatic atrial fibrillation. PMID- 1605160 TI - Chronic fatigue syndrome and psychiatric disorders. PMID- 1605161 TI - Bone density and L-thyroxine therapy. PMID- 1605162 TI - Anticardiolipin antibodies in northern Italian population with PMR/GCA. PMID- 1605163 TI - The importance of relating medicine and public health. AB - The historical division between medicine and public health is arbitrary and not in the best interest of the health of the American public. Combating the major causes of death and disability requires integration of medicine and public health by government and academia. PMID- 1605164 TI - Mast cells and calcium in severe uremic itching. AB - Mast cells may be more abundant in the tissues of uremic patients and may contribute to itching via mediator release. Because mast cell (MC) granule release may be inhibited by ultraviolet B (UVB) radiation, we investigated skin MC in the superficial dermis by quantitative histomorphometry before and after whole body UVB for uremic itching. Toluidine blue-stained 3.5 mm punch biopsy specimens were examined with a micrometer grid after separate coding. Upon entry to the study, itching dialysis patients indicated their itching intensity on a visual analog scale (0 to 10). Concurrent study of living, related kidney donors (controls, n = 11) and their recipients (n = 11) showed no differences in MC number per unit area. Compared to controls, skin MC number was not greater in itching dialysis patients (n = 20). MC number decreased after 2 months of UVB from 1.6 +/- 0.6 (standard deviation) to 1.0 +/- 0.7 (n = 11, p = 0.025). Pre-UVB total plasma calcium correlated directly with itching intensity, but not with MC number. Plasma phosphate and intact parathyrin level were not statistically related to itching or MC number. Of the 14 subjects that completed UVB, 8 had objective benefit, and mean itching intensity declined from 7.1/10 to 5.2/10 in the 14 subjects. The conclusion is that although skin MC number may decline with chronic UVB, MC number is not related to uremic itching, and hypercalcemia, but not elevation of parathyrin or plasma phosphate, relates statistically to severe uremic itching. PMID- 1605165 TI - The effects of nimodipine on cocaine toxicity. AB - The response to nimodipine as an inhibitor of cocaine toxicity was investigated in pentobarbital-anesthetized dogs and in isolated dog heart preparations at constant heart rates. Nimodipine (10 micrograms/kg) markedly decreased peripheral and coronary vascular resistance and increased cardiac output, cardiac work, and coronary blood flow. When corrected for the change in afterload, nimodipine had a positive inotropic response, as measured by +/- maximal dP/dt, in the cocaine depressed animal. Thus, cocaine toxicity was partially reversed by nimodipine. In the isolated heart preparation, nimodipine resulted in further cardiac depression similar to that seen with other calcium channel antagonists. PMID- 1605166 TI - Chronological assessment of asbestos exposure on cell composition in murine lung. AB - To elucidate immune pathogenic mechanisms in asbestosis, lung and spleen lymphoid cell populations were analyzed at defined time intervals (1, 2, 3, 6, and 12 weeks during exposure and 4, 24, and 48 weeks post-exposure) in asbestos-exposed and unexposed (control) mice. Polymorphonuclear leukocytes and macrophages were increased in the lung tissue histologic sections of asbestos-exposed mice compared to controls. No consistent changes were observed in percentages of lung or spleen helper, suppressor, or total lymphocyte populations after asbestos exposure. The numbers of B cells (identified by anti-IgG) in minced lung preparations of asbestos-exposed animals were increased after 12 weeks of exposure. There also was an increase in IgG production in asbestos-exposed mice after 12 weeks exposure and at 4 weeks post-exposure with a return to near baseline levels 24 and 48 weeks after initial exposure. Collectively, these studies demonstrate stimulatory effects of inhaled asbestos fibers on B cells and IgG production after 12 weeks of continuous inhalation of asbestos fibers in a dust generation chamber. PMID- 1605167 TI - Increased tyrosine protein kinase activity in hairy cell and monocytic leukemias. AB - Tyrosine protein kinases (TPK) help regulate cellular growth and differentiation. Several proto-oncogenes encode for protein products with associated tyrosine kinase activity. An assay for TPK activity was performed in cell extracts using a synthetic peptide substrate and [32P] adenosine triphosphate (ATP). TPK activity was elevated in K-562 cells, which possess an amplified c-abl oncogene, compared to normal blood mononuclear cells (K-562 = 9.37 +/- 1.72 [mean +/- standard deviation] pmol ATP/10(6) cells/min; normal = 1.14 +/- 0.46, p less than 0.01). TPK activity was measured in peripheral blood mononuclear cells from patients with hairy cell leukemia (HCL), myelomonocytic leukemia (MOL), acute myeloblastic leukemia (AML), and chronic lymphocytic leukemia (CLL). In patients with clinically active disease, elevated TPK activity was measured in mononuclear cells from five HCL patients (range 3.76-24.15) and from seven MOL patients. These elevated levels appeared to parallel disease activity, as low levels of TPK activity were measured in patients with inactive (treated) disease. Low levels of TPK were measured in mononuclear cells from active AML and CLL patients. Elevated TPK levels in patients with HCL and MOL may reflect the overexpression of a proto oncogene or increased growth factor activity in immature or rapidly dividing leukemic cells. Serial TPK levels in HCL and MOL patients correlated with change in disease activity. PMID- 1605168 TI - Case report: fatal seronegative rickettsial infection diagnosed by the polymerase chain reaction. AB - A previously healthy man presented with a five day history of high fever and headache, later followed by rash and the appearance of jaundice. On the second hospital day, he suddenly developed seizures, lapsed into a coma, and died. Polymerase chain reaction (PCR) amplification revealed a 434 base pairs DNA fragment common to the genome of typhus and spotted fever group rickettsiae in the patient's blood (estimated at about 1 x 10(2) organisms/ml), and to a lesser degree in the cerebrospinal fluid. However, serological tests for rickettsiae remained negative. PCR techniques may confirm the diagnosis at an early stage, even though the rickettsemia may be minimal and the patient seronegative. PMID- 1605169 TI - Case report: venous thromboembolism in AIDS. AB - Recently, the authors managed three patients with AIDS and venous thromboembolism. All three were active, ambulatory, and without known risk factors for pulmonary embolism or deep venous thrombosis. One patient had a low titer for IgG anticardiolipin antibody (1:13). Two had low normal values for free protein S, and the third patient had a very low value (5%). Clinicians caring for AIDS patients should be alert to the possibility that venous thromboembolism may complicate HIV infection. PMID- 1605170 TI - Case report: successful use of antifibrinolytic therapy in acquired factor VIII deficiency. AB - Acquired factor VIII deficiency is a rare immunologic disorder characterized by severe bleeding due to an antibody inhibitor directed against factor VIII. Treatment of this coagulopathy often is ineffective and costly. The authors report a case of acquired factor VIII deficiency in a patient who developed severe recurrent epistaxis. Antifibrinolytic therapy with epsilon aminocaproic acid (EACA) was used to control the epistaxis with excellent results. To the authors' knowledge, this is the first report of the efficacy of EACA therapy in acquired factor VIII deficiency. Use of antifibrinolytic therapy may represent a relatively safe, effective, and inexpensive approach to treating factor VIII inhibitors. PMID- 1605171 TI - Case report: gastrocolic fistula mimicking Zollinger-Ellison syndrome. AB - Fasting serum gastrin levels greater than 1000 pg/ml are said to establish the diagnosis of gastrinoma in a patient with peptic ulcer disease. The authors observed a patient with recurrent peptic ulcer disease, diarrhea, and a fasting serum gastrin of 1044 pg/ml who had a gastrocolic fistula, not the Zollinger Ellison syndrome. The provocative tests of gastrin secretion, including secretin infusion and standard meal test, were helpful in ruling out a gastrinoma. This is the first reported association of gastrocolic fistula and hypergastrinemia. The patient demonstrates that the differential diagnosis of markedly elevated serum gastrin should be expanded to include gastrocolic fistula. PMID- 1605172 TI - Case report: thrombotic thrombocytopenic purpura in a patient with polymyositis: therapeutic importance of early recognition and discussion of pathogenic mechanisms. AB - Thrombotic thrombocytopenic purpura (TTP) is characterized by the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic symptoms, and renal dysfunction. Thrombotic thrombocytopenic purpura has recently been reported in association with rheumatic diseases (RDs). The authors present a patient with TTP and polymyositis and speculate on the pathophysiology linking these two conditions. Thrombotic thrombocytopenic purpura and RDs may present with overlapping clinical and laboratory features. It is important to identify TTP as a cause of thrombocytopenia and hemolysis when occurring in patients with RDs since management, treatment, and prognosis differ. Early recognition and prompt institution of plasmapheresis may improve the outcome in patients with TTP. PMID- 1605173 TI - Case report: familial growth hormone deficiency associated with Bartter's syndrome. AB - Two children, a brother and a sister with growth retardation, and their short adult female sibling presented with isolated growth hormone deficiency. In addition, they had hypokalemic alkalosis and overactive renin-angiotensin aldosterone system. The mother of these three individuals has short stature plus growth hormone deficiency. Other members of the pedigree have average stature. All the patients are normotensive. In addition to potassium and magnesium administration, the children were treated with growth hormone for more than 12 months. The growth velocity more than doubled during the therapy period. The association between Bartter's syndrome and isolated familial growth hormone deficiency is of interest because of the combination of these two rare conditions. To our knowledge, there are no published growth hormone studies on Bartter's syndrome, which is also characterized by short stature. PMID- 1605175 TI - X-linked mental retardation 5. PMID- 1605174 TI - Laboratory markers of ethanol intake and abuse: a critical appraisal. AB - Laboratory markers for ethanol intake and abuse and chronic alcoholism currently in use have been critically reviewed. The merits and pitfalls of each test have been evaluated. The clinical use of the new test of carbohydrate-deficient transferrin has been particularly emphasized. Carbohydrate-deficient transferrin currently provides the highest specificity and sensitivity of all commonly used markers of alcoholism. PMID- 1605176 TI - Premutation for the Martin-Bell syndrome analyzed in a large Sardinian family: II. Neuropsychological and behavioral data. AB - We describe the neuropsychological and behavioral profiles of 48 critical members of a previously reported Sardinian pedigree [Filippi et al., 1991], in which the fully manifested Martin-Bell syndrome (MBS), observed among males of the latest generations, is clearly the result of step-wise mutational events occurred repeatedly along the X-chromosome pathway linking all of them to a common ancestress, who must have been heterozygous for a fragile X (FRAX) premutation. We found that the unquestionable presence in the family of normal transmitting males and females could not be determined on the basis of neuropsychological and behavioral data alone. However, we think that the large variation observed in the expression of most diagnostic parameters among the MBS patients and their close female relatives in this family, could by itself be a connotation of the genome instability which characterizes the FRAX region in pedigrees segregating for the FRAX premutation(s) and mutation(s). PMID- 1605177 TI - Verbal learning and memory among heterozygous fragile X females. AB - In this paper we report the results of a brief examination of verbal learning and memory in 20 heterozygous fragile X [fra(X)] positive females and in 2 control groups of 20 subjects each. One control group was composed of fra(X)-negative mothers (obligate carriers) and sisters of male probands with fra(X) syndrome, while the other consisted of 14 head injured and 6 learning disabled females. Intellectual functioning was assessed by means of the Wechsler scales, and learning was assessed by several different clinical memory tests. Significant differences were found between groups on measures of short-term memory and learning efficiency. Groups did not differ on measures of cued recall or delayed recall. The findings are consistent with other data and suggest the possibility that central information processing and/or specific encoding processes are defective in persons with fra(X). PMID- 1605178 TI - Cognitive profile in adult, normal intelligent female fragile X carriers. AB - Here we present the results of the study of the cognitive profile of 11 adult, normally intelligent female fragile X [fra(X)] carriers. In all individuals 3 types of testing were performed: full scale Wechsler Adult Intelligence Scale, a set of neuropsychological tests and an arithmetic achievement test. All 11 subjects showed an average to above-average intelligence but 10 of 11 performed better on the performance than on the verbal subscale. Neuropsychological tests suggest a dysfunction of the reticulo-thalamic axis with deficiency on tests requiring visual memory and a pronounced deficiency of attention skills combined with an impulsive way of completing tests. PMID- 1605179 TI - Mortality in the fragile X syndrome: preliminary data. AB - Mortality was studied among 348 males and 433 females who had or who carried the gene for the fragile X syndrome. The average age of death was about 12 years lower than in the general population for both men and women but this was likely a bias of ascertainment. The commonest causes of death were cardiovascular, cerebrovascular and malignant disease similar to those in the general population. No evidence for any specific disease susceptibility was found in this preliminary study. PMID- 1605180 TI - Sleep apnea in fragile X syndrome. AB - Seven subjects (age 6 to 21 years) with fragile X [fra(X)] were investigated for obstructive sleep apnea (OSA). After a structured interview, 4 of them underwent an overnight polygraphic study. The results indicate an increased risk for OSA among subjects with fra(X) (4/7). In 2 of the subjects polygraphic study indicated a severe OSA syndrome, whereas only mild and moderate severity was evident in the other two. Apnea in all 4 was associated with significant O2 desaturation. Episodes of prolonged expiratory apnea were reported in 2 of the subjects and confirmed by the polygraphic study in one. A continuous positive airway pressure (C-PAP) trial was successful in one of the two patients. It is suggested that subjects with fra(X) are at increased risk for OSA, and physicians should orientate their evaluation with this in mind. PMID- 1605181 TI - Prenatal detection of fra(X)(q27.3) in female identical twins: reliability of low level cytogenetic prenatal expression in females. AB - Recently, we detected fra(X)(q27.3) in amniocyte cultures from female identical twins. The pregnant woman did not exhibit fra(X)(q27.3) in whole blood cultures but was the sister of 2 affected brothers. DNA marker analyses showed that she was a carrier of FRAXA. Amniotic fluid cultures (AFCs) from twins A and B exhibited the fragile X [fra(X)] chromosome, but the level of cytogenetic expression was very low in twin A's AFCs. DNA marker studies indicated both twins were carriers of FRAXA. Peripheral umbilical blood sample (PUBS) cultures exhibited fra(X)(q27.3) at a frequency of about 10% for both twins. DNA fingerprinting indicated that the twins were identical, confirming the clinical impression, with a very thin separating amniotic membrane. To our knowledge, this is the only report of prenatal fra(X)(q27.3) detection in female identical twins, and the second report of identical twin detection [Rocchi et al., 1985]. We have diagnosed prenatally fra(X)(q27.3) in 5 female fetuses using AFCs. The average fra(X) frequency was 4% for these positive female fetuses with a range of 0.5% to 8.5%. Follow-up whole blood studies confirmed our original results at an average fra(X) frequency of 25%. IN CONCLUSION: 1. Low frequencies, perhaps 1 or 2%, or a few positive cells in AFCs, are likely to increase in magnitude when confirmed in whole blood cultures either pre- or postnatally. 2. It appears likely that the risk is low for false positive results in AFCs when low frequencies of fra(X)(q27.3) are encountered. PMID- 1605182 TI - Fra(X)(q27.2), the common fragile site, observed in only one of 760 cases studied for the fragile X syndrome. AB - Cell cultures from 760 whole blood, amniotic fluid, chorionic villus sample, and peripheral umbilical blood sample specimens were exposed to multiple fra(X)(q27.3) induction systems (none had aphidicolin). Fifty-three exhibited the rare fragile site, fra(X)(q27.3) or FRAXA, none of which demonstrated the common fragile site or FRAXD at band Xq27.2. Only one cell in one of the negative whole blood FUdR-treated cultures from a mentally retarded male showed FRAXD. Therefore, it appears that FRAXD occurs very rarely in cultures treated to induce FRAXA since only one positive cell was observed in over 88,000 analyzed. It appears that very low frequencies of fra(X)(q27) can be accounted for only in part by the presence of the common fragile site since only one of 9 cases, each with one fra(X)(q27) positive cell, exhibited FRAXD and the others were FRAXA. After confirmation of FRAXA with direct DNA testing in a large number of low frequency cases, it should be possible to rely on the detection of very low frequencies of fra(X)(q27.3), e.g., 1% with at least 2 positive cells. PMID- 1605183 TI - Factors which contribute to cytogenetic frequency of expression in families of fragile X females. AB - Frequency of expression in mentally retarded (MR) fragile X (fra[X]) males has been shown to be affected by genetic factors and laboratory procedures. Among MR females, factors that contribute to cytogenetic expression have been more problematic in part due to lower frequency of expression and X-inactivation. We examined fra(X) sisters to determine whether genetic factors affecting frequency of expression in sisters were comparable to those in brothers. Evaluations obtained from 2 data sets for a total of 66 families in which at least 2 affected brothers and/or 2 affected sisters were found cytogenetically positive were selected. Of 166 subjects chosen, 118 were male and 48 were female. Sibs were evaluated using an analysis of covariance (ANCOVA) with 2 factors (family, sex) adjusted for the covariate, age. Results indicated that interactive effects (family-by-sex) and main effects (family, sex, age) were significant but the interactive effect of age-by-sex was not. Consequently, one-way analyses of variance (ANOVA) of the effect of family were calculated separately for brothers and sisters. Correlation coefficients between family and cytogenetic frequency was r = .84 for brothers and r = .79 for sisters. Analysis of these coefficients indicated that they were not significantly different from one another (Z = 0.85, p greater than .40). While other factors may affect cytogenetic expression, whatever familial factors control frequency of expression among brothers appear to affect frequency of expression among sisters as well. PMID- 1605184 TI - Fra(X) prenatal diagnosis: are endoreduplicated and polyploid cells useful diagnostic criteria? AB - Cytogenetic and molecular protocols for prenatal ascertainment of the fragile X syndrome and the associated fragile site at Xq27.3 are relatively reliable. Any new diagnostic method which becomes available still elicits much interest. Kimchi Sarfaty et al. [1991] reported an increase in frequency of endoreduplication and polyploidy in fra(X) lymphoblasts and amniocytes when cultured with methotrexate (MTX) or fluorodeoxyuridine. Recently we analyzed the endoreduplication/polyploidy system using amniotic fluid, chorionic villus, and fibroblasts from fra(X) positive abortus cell cultures and from control samples. We observed no increased expression of endoreduplicated or polyploid cells in fra(X) positive amniocytes after exposure to MTX. The data presented here clearly dispute the value of endoreduplication/polyploid scoring as a diagnostic aid in prenatal fra(X) analysis. PMID- 1605185 TI - Effect of dialyzed sera on fragile X expression. PMID- 1605186 TI - Recent experience in prenatal diagnosis of fragile X. AB - Our experience with 48 prenatal fragile X cases (35 amniocenteses; 13 chorionic villi samplings) is summarized. Of these 48 cases, 18 consultands were known to be carriers of fragile X. No cytogenetic false negatives or positives were identified but 2 cases were uninterpretable. Cytogenetic recommendations include: 1) Ten or more days recovery time after growth in Chang medium, and 2) use of 3-4 media/inducer systems with duplicate harvests. Direct DNA probe testing will likely be the method of choice for prenatal diagnosis after sufficient data are collected to verify interpretation. Until then, both cytogenetic and direct DNA techniques should be utilized. PMID- 1605187 TI - Prenatal cytogenetic diagnosis of the fragile X chromosome: feasibility and speed of in situ clonal method in amniotic fluid cell tissue culture. AB - We have had experience with over 300 amniotic fluid specimens for prenatal diagnosis for the fragile X chromosome [fra(X)], and the flask method of tissue culture has been routinely utilized requiring extended tissue culture periods of 3-4 weeks. The use of the in situ clonal method of tissue culture for routine prenatal cytogenetic diagnosis of amniotic fluid cells has shortened tissue culture time and resulted in more rapid reporting; however, it has not been widely employed for fra(X) prenatal diagnosis. The simultaneous use of both methods of tissue culture has resulted in the detection of 2 cytogenetically fra(X) positive cases in amniotic fluid, with more rapid reporting and satisfactory expression of the fra(X) with the in situ clonal method. Thus, the use of the in situ clonal method of tissue culture for fra(X) prenatal diagnosis in amniotic fluid cells is feasible, faster and can serve as a more rapid cytogenetic adjunct to the newer DNA testing methods. PMID- 1605188 TI - Prenatal cytogenetic diagnosis of the fragile X syndrome in amniotic fluid: calculation of accuracy. AB - We have completed over 350 prenatal diagnoses for the fragile X [fra(X)] syndrome using amniotic fluid, chorion villus specimen (CVS), fetal blood sampling and molecular methods. A total of 300 amniotic fluid specimens have been received for prenatal diagnosis of the fra(X) syndrome. There was a documented family history of fra(X) in 170/300 amniotic fluid cases, and 23/170 were correctly identified as cytogenetically fra(X) positive (16 male; 7 female). Three males were false negative, and one female was fra(X) negative but identified as a probable carrier by RFLPs. No fra(X) positive or false-negative results were found in the absence of a fra(X) family history. Because the a priori risk for the fra(X) syndrome for each pregnancy was different and widely variable, the determination of the accuracy of the prenatal diagnosis results requires a consideration of these variables. On this basis, the calculated accuracy of prenatal cytogenetic diagnosis for the fra(X) syndrome is approximately 97%. This accuracy can be improved further with the simultaneous use of molecular methods, especially in view of recent developments. PMID- 1605189 TI - Prenatal diagnosis and carrier detection in fragile X. AB - Prenatal diagnosis was performed in 81 cases at risk for the fragile X syndrome. There were 12 fra(X)-positive cases, two of which showed low expression in cultured amniotic fluid cells. FUdR and high thymidine were used for induction of fra(X) (q27.3) expression in all cases. In 21 cases linkage studies were performed, 7 with probes for the loci DXS52, DXS98 and DXS105, 13 with probes for DXS369 and DXS296, DXS304 or DXS374 and one with the probe Do33 for DXS465. In 11 of these cases linkage analysis gave risk figures higher than 95% or lower than 5%, all in concordance with the cytogenetic findings. Discordance was found in three cases studied earlier, the two cases with low expression mentioned above and one cytogenetically normal case, which were now restudied with the new probes. RFLP-studies and linkage analysis was also performed for 24 cytogenetically fra(X)-negative females having a 50%, 25% or 12.5% risk of being carriers according to pedigree data. In 15 cases the risk dropped to 1% or less. Six of these women were pregnant and had asked for prenatal diagnosis but after genetic counseling prenatal diagnosis was avoided. PMID- 1605190 TI - Prenatal diagnosis of fragile X syndrome: results from parallel molecular and cytogenetic studies. AB - Since 1985, we have provided coordinated DNA-based and cytogenetic prenatal analysis for couples at risk for offspring afflicted with the fragile X [fra(X)] syndrome. To date, 40 pregnancies have been studied (22 males, 18 females). There were 5 males and 3 females identified to be at high risk by DNA but only 2 males and one female were demonstrated to be cytogenetically expressing the fra(X) prenatally. Of the other 3 males, one was a cytogenetic false negative (i.e. confirmed fra(X)+ at termination of pregnancy). The other 2 remain fra(X)- and are developing normally (undetected recombinants or non-penetrant male carriers). All fetuses at low risk were carried to term and are reported to be normal. PMID- 1605191 TI - Limited size of the fragile X site shown by fluorescence in situ hybridization. AB - Cosmids, isolated from a 475 kb YAC that spans the fragile X region, and the YAC itself, were used for fluorescence in situ hybridization (FISH) on metaphase chromosomes from fragile X patients. Cosmid 22.3, containing most of the hybrid translocation breakpoints, shows in situ hybridization signals distal and proximal from the fragile X site. We propose that the size of the fragile site is limited to 20 kb. PMID- 1605192 TI - Intragenic probe used for diagnostics in fragile X families. AB - The intragenic (FMR-1) probe pE5.1 was used for DNA analysis in fragile X families. With this probe fragments of altered size can be detected in female carriers, affected individuals and transmitting males. The length of the altered fragments was found to vary from one generation to another as well as between sibs. This instability of the DNA detected by pE5.1 was also seen in peripheral blood within single individuals. These phenomena are illustrated by 4 exemplary families segregating the fragile X syndrome. We demonstrate the diagnostic contribution of intragenic analysis to carrier detection as well as the identification of normal transmitting males carrying premutations. One of the families illustrates the passage of a premutation to a male through 2 generations. PMID- 1605193 TI - Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development. AB - The fragile X syndrome, the most common cause of inherited mental retardation, is characterized by unique genetic mechanisms, which include amplification of a CGG repeat and abnormal DNA methylation. We have proposed that 2 main types of mutations exist. Premutations do not cause mental retardation, and are characterized by an elongation of 70 to 500 bp, with little or no somatic heterogeneity and without abnormal methylation. Full mutations are associated with high risk of mental retardation, and consist of an amplification of 600 bp or more, with often extensive somatic heterogeneity, and with abnormal DNA methylation. To analyze whether the latter pattern is already established during fetal life, we have studied chorionic villi from 10 fetuses with a full mutation. In some cases we have compared them to corresponding fetal tissues. Our results indicate that somatic heterogeneity of the full mutation is established during (and possibly limited to) the very early stages of embryogenesis. This is supported by the extraordinary concordance in mutation patterns found in 2 sets of monozygotic twins (9 and 30 years old). While the methylation pattern specific of the inactive X chromosome appears rarely present on chorionic villi of normal females, the abnormal methylation characteristic of the full mutation was present in 8 of 9 male or female chorionic villi analyzed. This suggests that the methylation mechanisms responsible for establishing the inactive X chromosome pattern and the full mutation pattern are, at least in part, distinct. Our results validate the analysis of chorionic villi for direct prenatal diagnosis of the fragile X syndrome. PMID- 1605194 TI - Molecular studies of the fragile X syndrome. AB - We have studied families segregating for the fragile X syndrome for the presence of amplification of the CGG repeat sequence adjacent to the HpaII Tiny Fragment (HTF) island in the FMR-1 gene. We demonstrate that 138/143 fragile X positive, mentally retarded males show a characteristic smear of fragments corresponding to somatic variation in the amplification of the CGG sequence. In 7/8 normal transmitting males (NTM's), we show that there is a small amplification of sequence but no evidence for somatic variation. Defined mutated fragments in the size range found in NTM's are seen in daughters of NTM's. The daughters of these female carriers show either a defined fragment in the NTM size range, a defined larger fragment or a heterogeneous pattern of fragments. In the latter 2 cases the clinical phenotype of the females cannot easily be predicted, presumably because of variable X inactivation. In some families, the observed DNA genotype does not correlate with the phenotype; in others we demonstrate the occurrence of individuals with a mosaic DNA genotype. The implications of these data for diagnosis of the disease are discussed. PMID- 1605195 TI - Three families with high expression of a fragile site at Xq27.3, lack of anomalies at the FMR-1 CpG island, and no clear phenotypic association. AB - We report on 3 families where the presence and segregation at high frequency of a fragile Xq27.3 site is not associated with the mutations and methylation anomalies typically seen in the fragile X [Fra(X)] syndrome. In one family, a folate insensitive fragile site was associated with Robin sequence in the propositus. In a second family a fra(X) negative mother has two fra(X) positive sons (one mentally retarded and the other newborn). The third family presents very high expression of a folate sensitive site, unlinked to mental retardation, and was described previously by Voelckel et al. [1989]. The fragile sites in these or similar families recently described must be different from the one associated with the fra(X) syndrome. Their association with a clinical phenotype or with mental retardation is certainly not consistent, and may represent an ascertainment bias. However, the relatively high frequency with which they have been found among previously diagnosed fra(X) families suggests that, at least in some cases, the association with mental impairment may be significant. In two families reported up to now, a male with high expression of such variant fra(X) site failed to transmit it to his daughter, which may reflect an imprinting effect. Previously diagnosed families should be reinvestigated before direct DNA analysis is used for prenatal or carrier diagnosis of the fra(X) syndrome. PMID- 1605196 TI - Two families with Xq27.3 fragility, no detectable insert in the FMR-1 gene, mild mental impairment, and absence of the Martin-Bell phenotype. AB - In 2 families, propositi were investigated because of mild developmental delay and, in one case, behavior disorders. Seven males in the 2 families were found to have a fragile site at Xq27.3 but the usual insert in the FMR-1 gene was absent. The affected males had mild, or in some cases, no clear intellectual impairment and did not have the Martin-Bell phenotype. Carrier females in one family tended to show a high level of cytogenetic expression of the fragile site but were clinically normal. It is not yet clear whether these families have unusual mutations in the FMR-1 gene or whether their fragile sites are different, but cytogenetically indistinguishable from, that associated with inserts in the FMR-1 gene. PMID- 1605197 TI - Characterization of a highly polymorphic dinucleotide repeat 150 KB proximal to the fragile X site. AB - Fragile X [fra (X)] syndrome is a frequently encountered form of mental retardation and is inherited as an X-linked semi-dominant trait with reduced penetrance. We report here the characterization of a highly polymorphic dinucleotide repeat, DXS 548, which is approximately 150 kb proximal to the fra(X) site and the associated FMR-1 gene. DXS 548 is tightly linked to the fra (X) syndrome locus (FRAXA) without recombination (LOD = 9.07 with q of 0) in selected families with crossovers between FRAXA and very closely linked flanking markers. This dinucleotide repeat could be useful in determining the parental origin of a new fra (X) mutations and evaluating the role of FMR-1 in X-linked non-specific mental retardation. PMID- 1605198 TI - Analysis of mutations at the fragile X locus using the DNA probe Ox1.9. AB - In this study, 40 families segregating for fragile X [fra (X)] syndrome were examined for the presence of a mutation within the FMR-1 gene. Using the DNA probe Ox1.9, both carriers and affected individuals were found to contain an insertion/amplification-type of mutation with somatic instability. Variability in the size of the mutation, which ranged from less than 0.2 kb to approximately 13 kb, was observed both between individuals (even from the same family) and within individuals, who showed a smear rather than a discrete band(s) on Southern blot analysis. Transmission of the mutation by males resulted in little change of its size, while transmission by females usually resulted in an increase in size. Correlations were observed between the size of inserted/amplified DNA and the level of chromosome fragility and the presence or absence of mental impairment. Overall, a mutation was detected in 66 of 67 (99%) clinically affected males, in 12 of 13 (92%) transmitting males and in 95 of 112 (85%) carrier females. Equivocal results were obtained in 12 (11%) of the carrier females. No mutation was detected in 58 females and 33 males predicted to be normal by linkage, or in one female and 36 normal control males. These results strongly suggest that the mutation detected by Ox1.9 is closely associated with the cytogenetic and clinical expression of fra (X) syndrome. Additionally, the use of this probe along with other probe/enzyme combinations should provide a sensitive clinical assay for the detection of carriers of fra (X) syndrome. PMID- 1605199 TI - Parental origin of the fra(X) gene is a major determinant of the cytogenetic expression and the CGG repeat length in female carriers. AB - The fragile X [fra(X)] syndrome is the most frequent form of inherited mental retardation, and co-segregates with a fragile site at Xq27.3 as well as with insertion of a variable number of trinucleotide repeats in the 5'-end of the FMR 1 gene. As the fra(X) gene is transmitted by females as well as males, we have investigated whether the parental origin of the fra(X) gene has an effect upon the cytogenetic expression and CGG repeat length. An increased fragment length of 0.2-0.6 kb appeared to be associated with a very low expression or even complete absence of the fragile site as well as with a normal phenotype, and was seen mostly in cases of paternal inheritance. However, in most female carriers with the maternally inherited fra(X) gene we found dispersed fragments ranging from 1.4-6.5 kb or even complete absence of a hybridization signal. Within the group of female carriers with the maternally inherited fra(X) gene we found a statistically significant correlation between the level of the cytogenetic expression and the PstI restriction fragment length encompassing the CGG repeat. These data can be taken as indirect evidence that CGG repeat length and cytogenetic expression are causally related. PMID- 1605200 TI - Methylation and mutation patterns in the fragile X syndrome. AB - Chromosomes carrying the mutation causing the fragile X [fra(X)] syndrome have been shown to have an unstable DNA sequence close to or within the fragile site. The length variation is located within a DNA fragment containing a CGG trinucleotide repeat which is unstable in both mitosis and meiosis. We have used the probe StB12.3 from the region to analyze the mutations and the methylation patterns in 21 families segregating for the fra(X) syndrome. Among 40 fra(X) males all showed an abnormal pattern. The normal 2.8 kb band was absent in 36 individuals and replaced by a heterogeneous smear of larger size. The remaining four were shown to be "mosaics" with the presence of both mutated, unmethylated and mutated, methylated fragments. We found four normal transmitting males, one which was a great-grandson of another normal transmitting male indicating that the pre-mutation can remain stable through two meioses in the female. In nine fra(X) positive females the abnormal pattern consisted of a smear, usually seen in affected males, in addition to the normal bands. Five of these females were mentally normal. Of clinical importance is the prediction of mental impairment in females. We suggest that this is not made by the detection of the full mutation alone, but rather by the degree of methylation of the normal X chromosome. Our results suggest that difference of clinical expression in monozygotic twins may be correlated with difference in methylation pattern. Six out of 33 fra(X) negative females at risk were diagnosed as carriers. Our observations indicate that molecular heterogeneity is responsible for variable expression of the fra(X) syndrome in both males and females. PMID- 1605201 TI - Do sequences in Xq27.3 play a role in X inactivation? PMID- 1605202 TI - Longitudinal changes in IQ among fragile X males: clinical evidence of more than one mutation? AB - Longitudinal changes in IQ among mentally retarded (MR) fragile X [fra(x)] males have been reported previously. While age is associated with decline in IQ, not all males are so affected. This suggests that there may be more than one subtype of affected fra(X) male. Therefore, we examined the distribution of standardized difference scores (Zdiff) in IQ to determine if subjects were from an admixture of at least 2 populations. Cluster analysis of Zdiff scores was used to partition subjects into 2 groups. Goodness-of-fit tests indicated that scores were more likely to come from an admixture. Discriminant functions (DF) were calculated to determine predictive validity of Zdiff scores. To eliminate the effect of skewing, a power transform was applied to Zdiff scores and DFs recomputed. Zdiff and transformed scores provided similar results. The mean and variance for one group showed no differences in test-retest scores as would be expected from examining any population while the mean for the second group indicated significant decline in IQ nearly 4 standard errors below the first test score. These results suggest that there may be clinical evidence for 2 types of fra(X) mutation: One which causes MR but is static, and a second mutation which causes MR but is dynamic and contributes to an apparent longitudinal decline in cognitive function. PMID- 1605203 TI - Concerning the role of X-inactivation and DNA methylation in fragile X syndrome. AB - Elucidation of the role of DNA methylation in X chromosome inactivation along with recent studies of the fragile X mutation suggests that DNA methylation is likely to be a late event in the pathogenesis of the fragile X syndrome. Thus far, the evidence does not support suggestions that an impediment to X reactivation and failure to demethylate the inactive X in oocytes is responsible for silencing the fragile X. The role of DNA methylation is probably secondary to amplification of the CGG repeat to a critical size whether on active or inactive X. Further studies are needed to determine if late replication of the inactive X predisposes the locus on that chromosome to more extensive amplification. PMID- 1605204 TI - Fragile X mental retardation and the iduronate sulphatase locus: testing Laird's model of fra(X) inheritance. AB - Fragile X [fra(X)] mental retardation syndrome is the most frequent familial cause of mental handicap. The clinical phenotype is associated with a rare fragile site at Xq27.3. The mutation underlying the disorder, an insertion into the FMR-1 gene, has been characterized, but the pathogenesis of the condition is obscure and the pattern of inheritance is still not fully understood. One model of fra(X) pathogenesis was proposed by Laird in 1987, suggesting that the fra(X) mutation acts as a cis-acting, local block to the pre-oogenesis reactivation of the inactivated X chromosome. To test this model, we examined the activity of the F8, F9 and iduronate sulphatase (IDS) loci. The level of IDS in the serum of fra(X) males was found to be very significantly reduced in the fra(X) group when compared to that of control males: this lends support to Laird's model of fra(X) pathogenesis. However, we detected no methylation differences between fra(X) and control samples at the IDS locus, although such changes are known in fra(X) males at sites closer to the fragile site. Thus the mechanism of the reduction in IDS activity has not been identified. PMID- 1605205 TI - Validation of linkage-based DNA-diagnosis of fragile X gene carriers with the CGG repeat probe. AB - We have evaluated our carrier testing for the fragile X [fra(X)] syndrome, which was based on linked DNA markers, with the direct analysis of the CGG repeat sequence in the fra(X) gene. PstI and EcoRI blots were hybridized with a probe derived from the region just 3' of the CGG repeat in Xq27.3. We found the mutation analysis to be very sensitive as all 71 obligate gene carriers as well as 135 fra(X) patients tested showed evidence for an increased restriction fragment length encompassing the CGG repeat sequence with or without dispersion of the hybridization signal (mosaicism). Based on linked DNA markers, 6 out of 50 cytogenetic negative and mentally normal males at risk and 15 of 72 females at risk had inherited the allele at risk. All of these diagnoses could be confirmed by analysis of the CGG repeat length. PMID- 1605206 TI - New York State screening program for fragile X syndrome: a progress report. AB - New York State has established a program to screen post-pubertal mentally retarded males for the fragile X [fra(X)] syndrome. The goal of the program is to identify affected males and inform their families of the diagnosis. Females in these families who are at risk for inheriting the mutation will then be able to determine their carrier status and consider that information in making reproductive decisions. Males were evaluated for 10 features of the syndrome by physicians and nurses throughout the state; cytogenetic analysis was carried out on a subset of this population. A total of 1332 males has been screened and chromosome studies have been completed for 489. Forty-three (9%) were positive for fra(X), and an additional 11 other chromosome abnormalities were identified. The 43 patients belonged to 38 families. Of the 24 families who were informed of the diagnosis, 12 consulted genetic counseling centers for follow-up studies and 12 did not. PMID- 1605207 TI - Fragile X screening program in a Spanish region. AB - In a Spanish region with a population of one million, we screened 371 mentally retarded males, who had no previous diagnosis for fragile X [fra(X))] syndrome. Fifty-three of the 371 males were fra(X) positive. Of these 44 of 362 or 12.1% were unrelated. Family studies identified a large number of obligate carriers and women at risk for being carriers who were given genetic counseling including prenatal diagnostic information. Considering the age of the carriers and the fertility rate, 23 affected males could be born to these women. The prevention potential of this program suggests that it is highly cost-effective. PMID- 1605208 TI - Notes on the population genetics of fragile X syndrome. AB - Our analysis of fragile X-inactivation in normal and mentally retarded heterozygotes led us to conclude that a fraction of female carriers of the imprinted (fully mutated) allele is phenotypically normal as a consequence of X inactivation. Taking this into account, we derived equilibrium equations for the fragile X [fra(X)] genotype frequencies. We also showed that small variations in the value of s (selection coefficient of affected heterozygotes) and r (imprinting rate during oogenesis) affect genotype ratios significantly. PMID- 1605209 TI - High prevalence of the fra(X) syndrome cannot be explained by a high mutation rate. AB - The overall prevalence of the fragile X [fra(X)] mutation, as determined by population studies, is approximately 1 in 850 [Gustavson et al., 1986; Webb et al., 1986]. This prevalence suggests a very high mutation rate which, in turn, suggests that many patients have to represent sporadic cases. In order to obtain an accurate estimate of the proportion of sporadic cases, we performed genealogic, cytogenetic and DNA linkage studies as well as direct analysis of the CGG repeat in relatives of 84 fra(X) probands. We did not find any evidence for the presence of sporadic cases. In 11 probands consanguinity could be proven by the detection of common ancestors, in 5 related families up to 9 generations ago. In the other 6 related families the mutation could be traced back 4-6 generations. In 3 or more generation families we were able to demonstrate that half of the probands carried the grandpaternal fra(X) gene. These results imply that rather than a high mutation rate, both Normal Transmitting Males (NTM's) and mentally normal female carriers contribute considerably to the high prevalence of the fra(X) syndrome. PMID- 1605210 TI - Behavioral phenotype of fragile X syndrome: DSM-III-R autistic behavior in male children. AB - Comparison of 34 fragile X [(fra(X)] male children (age 3-18 years) with 32 IQ- and age-matched, non-fra(X) male control children was conducted using specific DSM-III-R criteria for autism. Statistical analyses supported predictions that fra(X) males show increased dysfunction in peer social play, nonverbal communication (e.g., gaze aversion, gesturing), verbal communication (e.g., rate, volume, word/phrase perseveration), and repetitive motor behaviors (e.g., handflapping, rocking). There was a trend for fra(X) children to show abnormal responsivity to sensory stimuli as well such as oversensitivity to sound and increased mouthing or smelling of objects. The investigation supports the contention that fra(X) males manifest a specific subset of behaviors from the autistic spectrum. Implications for treatment are discussed. PMID- 1605211 TI - Study of individuals possibly affected with the fragile X syndrome in a large Swedish family in the 18th to 20th centuries. PMID- 1605212 TI - Collaborative prospective study of the fragile X syndrome: one-year progress report. AB - A prospective study of the fragile X syndrome [fra(X)] was initiated one year ago to refine the estimates of recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the conceptus of women known to carry the fra(X) gene or of mothers of an isolated case. To date, information on 261 women and their conceptuses was ascertained primarily through prenatal diagnosis; these data are summarized here. Although tests of significance were limited due to small sample sizes in subgroups, the following trends were observed: 1) the penetrance of fra(X) site expression was 80% in both male and female conceptuses suggesting that fra(X) site expression is equally penetrant early in development; 2) the sex ratio at the time of prenatal diagnosis did not differ from one, indicating that selection against fra(X) fetuses, if any, does not differ among sexes; 3) the recurrence risk among offspring of borderline/mildly retarded mothers was higher than that among offspring of intellectually normal mothers; 4) the recurrence risk in offspring did not differ based on the mother's fra(X) site expression; and 5) the recurrence risk in offspring of mothers with isolated cases was slightly less (34%) than that of obligate carrier mothers (41%) although this was not significant. The potential use of these prospective data on the fra(X) syndrome is emphasized. PMID- 1605213 TI - Penetrance estimate of the fra(X) gene using Pointer versus direct estimate. AB - Direct estimate of the penetrance of the fra(X) gene was compared with the estimate using the Pointer computer program. Direct estimate gave overall penetrances of 85% for male and 64% for female carriers. The estimates calculated by the Pointer program were 82% for males and 38% for females. It is argued that the use of the Pointer program gives incorrect estimates of the penetrance of the fra(X) gene. PMID- 1605214 TI - Penetrance of fra(X) gene: influence of grandparental origin of the gene, mental status of the carrier mother, and presence of a normal transmitting male. AB - Previous studies have indicated that the fragile X [fra(X)] gene does not show full penetrance (mental impairment) in carrier females or "carrier" males. The phenomenon of non-expressing carrier males distinguishes the fra(X) syndrome from all other known X-linked disorders. Moreover, penetrance of the fra(X) gene apparently does not show random distribution within fra(X) families, but seems to be reduced in sibs of normal transmitting males (NTM's). The availability of many large multigeneration fra(X) families, studied by cytogenetic and DNA analyses, enabled us to refine the estimates of the penetrance. From our data we conclude that the penetrance in daughters of carrier females is determined by the mental status of the mother. In sons of carrier females, the observed penetrance appears to be influenced by the grandparental origin of the gene as well as by the mental status of the mother. However, in contrast with the average penetrance, we observed a strongly reduced penetrance of the fra(X) gene in brothers (14%) and sisters (21%) of NTM's. These findings have profound implications for genetic counseling. PMID- 1605215 TI - XLMR genes: update 1992. AB - Up to now, we have identified 77 X-linked conditions in which mental retardation is the primary or a major component manifestation. These conditions were subdivided into 2 categories, designated respectively "X-linked mental retardation syndromes" and "Non-specific X-linked mental retardation". Forty genes have been regionally mapped onto the X chromosome. However, in several instances the data were derived from a single family and most lod scores were less than 3.0. PMID- 1605216 TI - Nomenclature guidelines for X-linked mental retardation. AB - Nomenclature guidelines are proposed for non-specific and for syndromal forms of X-linked mental retardation. Non-specific mental retardations (MRX) are given unique symbols for each family (MRX1, MRX2, MRX3 ...). Syndromal mental retardations (MRXS) which do not as yet have specific symbols are given unique interim symbols for each syndrome (MRXS1, MRXS2, MRXS3 ...). The prerequisite for assignment of serial MRX and MRXS gene symbols is a minimum lod score (or multipoint lod score) of +2 between the MR locus and one or more X chromosome markers. Prior approval of availability for proposed gene symbols must be obtained from the Nomenclature Committee of the Human Gene Mapping Workshops. PMID- 1605217 TI - Localization of non-specific X-linked mental retardation genes. AB - Gene localization was determined by linkage analysis in 5 families with non specific X-linked mental retardation (MRX) and were MRX1, Xp11.4-q21.31; MRX10, Xp21.3-p11.4; MRX11, Xp21.3-p11.22; MRX12, Xp21.3-q21.1; and MRX13, Xp22.3 q21.22. Four of these localizations cross the dystrophin brain promoter, a candidate locus for MRX. None of the affected individuals who were tested showed variation suggestive of a deletion. No consistent clinical features were observed between or within 4 of the 5 families. In MRX12, prematurity or low birth weight, hypotelorism and short stature were seen in several affected males. Heterozygote manifestations occurred in 3 families. There was no evidence to suggest involvement of the same gene in more than one family, nor to clinically separate these families into distinct genetic entities. Non-overlapping localizations for MRX1 and MRX10 demonstrate the existence of at least 2 separate loci among these 5 families. PMID- 1605218 TI - MASA syndrome: delineation of the clinical spectrum at prepubertal age. AB - Here we describe the clinical and neurological findings in 2 brothers with MASA syndrome and the changes in phenotypic and neurological findings during the prepubertal period. MASA syndrome seems to be an X-linked mental retardation syndrome with progressively appearing manifestations and neurological signs, making clinical diagnosis before age 4 years difficult. PMID- 1605219 TI - Clasped-thumb mental retardation (MASA) syndrome: confirmation of linkage to Xq28. AB - We describe a 5-generation Hispanic family with 13 males and 1 female affected with MASA syndrome. The proposita, a 17-year-old female, and her affected male relatives shared many of the cognate manifestations--mental retardation (14/14), aphasia or delayed speech (13/13), shuffling gait (8/13), adduction of thumbs (14/14)--as well as scoliosis (2/13) and increased deep tendon reflexes in the lower extremities (10/13). Southern analysis with the polymorphic DNA probes DXS14 (Xp11), DXS72 (Xq21), and F8C (Xq28) confirmed linkage to the Xq28 region with a maximum lod score of 3.01 for this family. PMID- 1605220 TI - Use of linkage data obtained in single families: prenatal diagnosis of a new X linked mental retardation syndrome. AB - Prenatal diagnosis was requested by an obligate carrier of a new syndrome of X linked mental retardation. There was close linkage between the disease gene and the hypervariable VNTR marker DXS255 with a lod score of 4.82 at o = 0 (90% support interval 0.00-0.12). When the request for prenatal diagnosis was made, additional family members were examined, resulting in an amended lod score of 6.71 at o = 0.0 (90% support interval 0.00-0.09). There were no informative flanking markers at the time of the request for prenatal diagnosis; hence it proceeded by 2 point linkage analysis. The fetus was female with a carrier risk in the interval of 91-100%. Given the limitations of the mapping data available for this disorder at the time of the request, the options of accepting or rejecting this as a case for prenatal diagnosis were carefully considered. Whilst prenatal diagnosis based on fetal sexing would be sufficient to prevent the birth of an affected child, the magnitude of the known two-point lod score between DXS255 and the disease gene provided a means for diagnosis with an accuracy between 91 and 100%. PMID- 1605221 TI - Aarskog syndrome: the changing phenotype with age. AB - We describe the Leuven experience with 52 males with Aarskog syndrome particularly with respect to clinical variability, changing phenotype with age, and previously unreported signs. At least 30% of affected males were mentally retarded, two thirds of them at the level of slight mental handicap. Hyperactive behavior and symptoms of attention deficit disorders were frequently observed (61% of the mentally normal and 84% of the mentally subnormal), but regressed completely after the age of 12 to 14 years. The social integration and functioning as adults is satisfactory. Postpubertal males with Aarskog syndrome have only minor remnant manifestations of the prepubertal phenotype, making clinical diagnosis in adults extremely difficult. PMID- 1605222 TI - Simpson-Golabi-Behmel syndrome associated with renal dysplasia and embryonal tumor: localization of the gene to Xqcen-q21. AB - We report 6 affected males in a 5-generation family with x-linked Simpson-Golabi Behmel (SGB) syndrome. All had pre- and postnatal overgrowth with 2 adult males attaining heights over 195 cm. Other features included "coarse" face with hypertelorism, broad nasal root, cleft palate, full lips with a midline groove of the lower lip, grooved tongue with tongue tie, prominent mandible, congenital heart defects, arrhythmias, supernumerary nipples, splenomegaly, large dysplastic kidneys, cryptorchidism, hypospadias, skeletal abnormalities and postaxial hexadactyly. All affected individuals were of normal intelligence. One boy died at age 19 months of a neuroblastoma. The putative origin of the gene in this family was the maternal great grandmother of the propositus. Eight carrier females, who showed varying manifestations of the gene, have been identified. Anthropometric analysis has identified preliminary characteristic craniofacial dimensions in this syndrome. Molecular studies have shown a maximal lod score of 2.81 with no recombinants observed for the SGB-DXYS68 pairing, mapping the disorder to Xqcen-Xq21.3. PMID- 1605223 TI - Linkage of nonspecific X-linked mental retardation to Xq21.31. AB - Mental retardation unassociated with the Fragile X syndrome accounts for up to 60% of patients with X-linked mental retardation. In this investigation, we report on a family with mild non-specific X-linked mental retardation (MRX) without other apparent phenotypic abnormalities. Linkage analysis on 27 relatives using 18 polymorphic markers spanning the X-chromosome demonstrated close linkage to DXYS1 with a peak LOD score of 2.14 at a theta of 0. Numerous families with various types of MRX have now been studied by other investigators using molecular genetic techniques. In addition to the family described in this report, a number of these have demonstrated linkage to the DXYS1 locus. These data suggest that a gene for mental retardation may exist in the region of DXYS1. Alternatively, this area of the X-chromosome may harbor multiple different but closely linked genes which cause the various types of MRX. PMID- 1605224 TI - Congenital X-linked ataxia, progressive myoclonic encephalopathy, macular degeneration and recurrent infections. AB - We report on 2 boys (maternal cousins), with severe congenital ataxia with generalized hypotonia, psychomotor retardation and recurrent bronchopulmonary infections. Later, they developed myoclonic encephalopathy and macular degeneration. Serial brain imaging investigations showed a cyst of the septum pellucidum, persistence of the cavum vergae, corpus callosum and cerebellar vermis hypoplasia without cortical atrophy. In the maternal pedigree, 5 males had recurrent bronchopneumonia associated with severe congenital hypotonia and died during the first years of life. Neurophysiological studies, including nerve conduction velocities, brainstem auditory evoked responses, somatosensory evoked potentials were normal. Electroretinogram showed normal wave morphology. Visual evoked potentials were mildly impaired. Extensive screening for metabolic disease gave normal results. Immunologic investigations showed normal T and B cell number, T cell function and immunoglobulin levels in both patients with a reduced level of IgG2 subclass in one. PMID- 1605225 TI - New XLMR syndrome with characteristic face, hypogenitalism, congenital hypotonia and pachygyria. AB - A previously unreported X-linked MCA/MR syndrome is described in 4 members of a large family. Phenotypic manifestations include mental retardation, microcephaly, failure to thrive, severe congenital hypotonia, characteristic face, hypogenitalism, pachygyria. This appears to be an X-linked dominant trait with decreased penetrance and expressivity in carrier females. PMID- 1605226 TI - New X-linked syndrome with seizures, acquired micrencephaly, and agenesis of the corpus callosum. AB - We report on 4 generations in a family with 3 living males, 3 males who died in infancy, and 3 females with neurologic impairment and agenesis of the corpus callosum (ACC). Manifestations in the surviving males include severe acquired micrencephaly, mental retardation, limb contractures, scoliosis, tapered digits with hyperconvex nails, a characteristic face with large eyes, prominent supraorbital ridges, synophris, optic atrophy, broad alveolar ridges and seizures. Urologic anomalies include renal dysplasia, cryptorchidism, and hypospadias. Two affected females were less severely impaired and continued to be socially responsive as adults, but had spastic quadriplegia and seizures. One obligate heterozygote was retarded with emotional problems while another obligate carrier female and her daughter were clinically normal. Pedigree analysis suggested X-linked inheritance with variable expression in females. These findings are inconsistent with the well-described X-linked conditions with ACC including FG syndrome and Aicairdi syndrome. ACC has not been described in Coffin Lowry syndrome, a condition with similar clinical findings, which also demonstrates marked variability of expression in carrier females. In order to assist in carrier determination, brain imaging studies and DNA linkage analysis of the affected relatives was performed. We found a spectrum of agenesis of the corpus callosum with the most severe manifestations in the most severely affected males. DNA analysis using a series of X-linked probes suggests linkage with a LOD score of 1.26 at theta = 0 to a region between p 11.3 and p 21.3. PMID- 1605227 TI - MRX8: an X-linked mental retardation condition with linkage to Xq21. AB - A family in which 6 males have X-linked mental retardation has been studied with polymorphic DNA probes. The males differ from unaffected males only in impaired intellect and in smaller head size. The gene that causes mental retardation in the family appears to be located in band Xq21 on the basis of linkage with 3 markers: DXS250, DXS345 and DXS3 (theta max = 0.00; Zmax = 1.6). A multipoint lod score of 2.36 was obtain with no recombination relative to DXS326 in Xq21. This family is considered to have nonspecific X-linked mental retardation and has been given the designation MRX8. PMID- 1605228 TI - Is autism associated with the fragile X syndrome? AB - In addition to mental retardation (MR), fragile X [fra(X)] has been associated with other developmental disabilities, autism in particular. Recently, several studies have concluded that the association of fra(X) with autism is at best weak and perhaps nonexistent. This study examined reports of previously published data from an epidemiological perspective to determine if the prevalence of fra(X) among autistic males was significantly different from that among MR males. Nineteen studies of autistic males and 21 studies of MR males were analyzed from 59 examined. Of 5601 MR males tested, 307 (5.5%) were cytogenetically positive. Of 1006 autistic males, 54 (5.4%) were positive. Analysis indicated no statistical difference between these proportions (Z = 0.014; p greater than .50). An odds ratio (OR) was also computed to determine the risk of autism from fra(X). Estimated OR approximately 1.0 [0.73, 1.32]. Attributable risk (AR), the proportionate excess risk of autism associated with exposure to fra(X) was AR approximately 0.0. That is, there was no attributable risk of autism from fra(X). The association of fra(X) with autism may reflect the association with MR that generally accompanies autism, as several earlier reports have noted. However, the similarity in prevalence of fra(X) among autistic and MR males may be biased in the studies which find no instances of fra(X) among autistic males represent 12% of the pooled sample. PMID- 1605229 TI - X-linked mental retardation and characteristic physical features in two brothers with duplication Xp22-Xpter. AB - Two brothers are reported who share mental retardation, conjunctival teleangectasias (mainly equatorial) and characteristic flat face with small mouth and thin prolabia. At the neuropsychological examination, the older brother at 14 years showed a full scale IQ of 40 (WISC), with verbal IQ 45 and performance IQ 44. The younger brother at 7 years showed a full scale IQ of 58 (WPPSI), with verbal IQ 67 and performance IQ 55. Chromosome studies showed a duplication Xp22 Xpter in both brothers and in the inactivated X of their mother. The anomaly was not present in a 3rd healthy brother and in other healthy relatives. The mother has normal intelligence and did not present any of the physical features of her affected sons. PMID- 1605230 TI - Spastic paraplegia with iron deposits in the basal ganglia: a new X-linked mental retardation syndrome. AB - We report on a family with X-linked mental retardation (XLMR) and severe spastic paraplegia. Appearance is normal but there is severe involvement of the lower limbs (affected relatives never walked), with minimal involvement of the upper limbs and unusual MRI findings including macrogyria, white matter hypoplasia, lack of myelination and a markedly increased paramagnetic signal suggestive of iron deposition. Linkage studies documented possible linkage, with no recombination, between the disease locus and DXS424. A 7-point linkage analysis yielded a maximum LOD score of 1.9, (theta = 0.00) for three loci spanning Xq22 q25. The combination of the unusual clinical and MRI findings and the tentative localization to a region different than other XLMR syndromes with spastic paraplegia, provide good evidence that this is a new XLMR syndrome. PMID- 1605231 TI - Allan-Herndon-Dudley syndrome: clinical and linkage studies on a second family. AB - We restudied a family with X-linked mental retardation (XLMR) originally reported in abstract form by Davis et al. [1981]. All 8 living affected males were examined. Characteristics included severe mental retardation, spastic paraplegia, dysarthria, muscle wasting, scoliosis, broad shallow pectus excavatum, long face, large ears with minor modeling anomalies, foot deformities, joint contractures, and neck drop. Stature, OFC, testicular volume, high resolution chromosome and fragile X studies, and plasma amino acids were all normal. Their manifestations closely resemble those of a large family with XLMR originally reported by Allan et al. [1944] and restudied by Stevenson et al. [1990]. This condition has been termed the Allan-Herndon-Dudley syndrome (AHDS). As AHDS has been mapped to Xq21, mapping studies were undertaken to determine if this family maps to the same location. These studies demonstrate tight linkage to Xq21, with a maximum lod score of 2.88 obtained with probe pX65H7 (DXS72). Multipoint analysis located the mutant gene quite close to pX65H7 (multipoint Z = 4.14), slightly more proximal in Xq21 than was suggested by the data from the original AHDS family. It appears likely that this family is the second reported family with AHDS. PMID- 1605232 TI - New X-linked syndrome with apraxia, ataxia, and mental deficiency: clinical, cytogenetic and neuropsychological studies in two Danish families. AB - In 2 unrelated families 9 males presented with ataxia, apraxia, and neuropsychological abnormalities or mental deficiency, inherited as an X-linked recessive syndrome with partial clinical expression in obligate female carriers. The symptoms were present in early childhood and were non-progressive. Additional findings in 2 males were congenital "club-feet" and generalized seizures. The affected males were 13-62 years old at the time of our examination. Chromosome abnormalities including fragile X fra(X) could not be demonstrated in any case. Results of metabolic screenings were also normal. The clinical picture with X linked recessive inheritance distinguishes this syndrome from previously described inherited hereditary ataxias. PMID- 1605233 TI - Fifth international workshop on fragile X and X-linked mental retardation. PMID- 1605234 TI - Neuropsychological studies in families with fragile-X negative X-linked mental retardation. AB - Neuropsychological studies were performed in 82 subjects of 12 families with x linked, fragile X negative, mental retardation (MR). Subjects were examined with Wechsler tests (WPPSI, WISC-R or WAIS, according to their capabilities), Progressive Matrices, Bender or Santucci and memory tests. Physical findings in 5 families were characterised by micro-orchidism (MiO), microcephaly (MiC), short stature (SS) and non-specific facial features (XMR +/- MiO +/- MiC +/- SS). The 11 males with MR had a very low IQ, ranging from 13 to 37 (mean 21.2 +/- 8.8); this did not constitute a profile definition. Among the females of their families, 4 had subnormal or borderline IQ, respectively 74, 66, 38 and 37. A second group (2 families) had MiO but with normal stature and occipito-frontal circumference (XMR +/- MiO). The 7 males with MR had an IQ ranging from 24 to 43 (mean 35.1 +/- 5.8) and showed frequently better results in performance than in verbal subtests. In these 2 families, 5 females had subnormal or borderline IQ, respectively 77, 72, 71, 70 and 20. In the 5 families of the third group, XMR +/- MaO (fraX-), several affected males had macro-orchidism (MaO) and facial changes similar to those of fragile X syndrome. IQ variability, also in the same family (e.g.: the 3 brothers of family 3 had, respectively, an IQ of 26, 28 and 68; and 2 brothers of family 1 had an IQ of 13 and 63) and different profiles. Two females were severely affected (IQ 16 and 24), while another 4 had an IQ, respectively, of 63, 69, 71 and 72. PMID- 1605235 TI - Behavior phenotype of the fragile X syndrome. PMID- 1605236 TI - Brief screening questionnaire for determining affected state in fragile X syndrome: a consensus recommendation. AB - New molecular research has provided strong evidence for different forms of the fragile X mutation. These findings suggest the need to develop a more standardized and sensitive method for determining neurobehavioral effects of the fragile X gene(s), particularly for molecular studies of patients who do not have obvious mental retardation. This report describes a brief screening questionnaire designed to increase the detection of neurobehavioral dysfunction in individuals from fragile X families who are included in new molecular studies. Improved detection of the affected state in fragile X syndrome will allow more valid clinical data to be correlated with the important molecular information currently being collected. PMID- 1605237 TI - Expressive semantic deficit in the productive language of males with fragile X syndrome. AB - Eleven males with fragile x syndrome [fra(X)] between the ages of 6 and 41, with an average communication age of 4 years 4 months and 11 normally developing 4 year old boys were administered a sentence completion task that assessed expressive semantic competence. The fra(X) males produced significantly more semantic errors than the normally developing 4 year children. Additionally, it was shown that sentences which could be correctly completed by a wider choice of words affected fra(X) males more than the nondisabled children. These 2 results suggest that the expressive semantic system is an area of specific deficit in fra(X) males. PMID- 1605238 TI - Abnormal behaviors of young girls with fragile X syndrome. AB - Mothers of 38 young girls with fragile X [fra (X)] between the ages of 4 and 11 years filled out the Child Behavior Checklist. Forty-seven percent of the girls had T scores greater than 70 on the hyperactive and social withdrawal scales. Between 26% and 15% of the girls also had high T scores on the depressed scale, on the schizoid-obsessive scale (for 6 to 11 year olds), on the schizoid or anxious scale (for 4 and 5 year olds), and on the aggressive scale. Although a high score on a scale of the Child Behavior Checklist does not constitute a medical diagnosis, it can alert clinicians to abnormal behaviors that warrant further assessment. These behaviors may also alert the clinician to the possibility of fra(X) syndrome when they are seen in their patients. The high percentage of girls with fra(X), who seem to have abnormal behaviors, provides good reason to diagnose them in their early years, not just for genetic counseling purposes, but so that they can receive appropriate intervention services. PMID- 1605239 TI - Problem solving limitations among cytogenetically expressing fragile X women. AB - Neurocognitive deficits among fragile X individuals have been reported for both high and low functioning individuals. Recent findings from our research suggest a specific neurocognitive phenotype among fragile X women that is characterized by deficits on tests of frontal lobe functioning. In this paper, we examine in more detail the performance of 10 cytogenetically expressing women and 10 control women on 2 problem solving measures considered sensitive to frontal lobe functions: the Contingency Naming Test and the Tower of Hanoi. The results pertaining to each test suggest that fragile X women, relative to control women, are less able to solve a problem when the difficulty of the problem is increased by requiring simultaneous consideration of additional information. These findings have important implications for remediation strategies designed for affected fragile X individuals. PMID- 1605240 TI - Mode of inheritance influences behavioral expression and molecular control of cognitive deficits in female carriers of the fragile X syndrome. AB - The effect of mode of inheritance on expression of fragile X syndrome [fra(X)] was investigated in nonretarded female carriers. Examination included cognitive and molecular measures. A priori predictions about cognitive impairment and size of an unstable region of DNA containing a CGG repeat on the X chromosome were tested in age and education matched heterozygotes grouped according to parental inheritance. Nine carriers with a maternal fra(X) chromosome, 11 carriers with a paternal fra(X) chromosome and 15 control mothers of children with non X-linked developmental disabilities were tested. Inheritance was established through DNA linkage analysis. Cognitive skills were assessed using the Wechsler Adult Intelligence Scale-Revised and the Benton Visual Retention Test. Molecular status was assessed by Southern blot analysis of genomic DNA digested with Eco RI and Eag I, and probed with StB 12.3. Results supported the inheritance models' predictions. Heterozygotes who inherited the fra(X) from their fathers appeared to be a homogeneous group. They were indistinguishable from controls on cognitive measures and all had genomic insertions of less than 500 base pairs. In contrast, heterozygotes who inherited the fra(X) chromosome from their mothers appeared to be made up of 2 sub-populations. They were as a group deficient in measures of attention and visual memory, but not other measures, with scores of some women consistently below the other subjects. Further, they had some members with greater than 500 base pair inserts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605241 TI - Prenatally detected fragile X females: long-term follow-up studies show high risk of mental impairment. AB - The prenatal detection of a positive fragile X [fra(X)] female raises difficult counseling issues. In order to address questions regarding the long term outlook, we have conducted follow-up studies on 4 fra(X) positive females which were carried to term. Three were prenatally detected, and one was a false negative. The subjects were between 3 and 7 years old when follow-up investigation of mental status was conducted. The first case age, 6 and 9/12 years, had an IQ of 106. On measures of achievement she had some difficulty with arithmetic. The second and third cases were clearly affected. They were judged to be mildly to moderately mentally retarded. The fourth case was borderline normal. The prenatal amniocentesis cytogenetic frequencies had a mean of 3.74% (range 0-8.5%). On postnatal follow-up testing of blood, the mean cytogenetic frequency increased to 31.75% (range 24-47%), an 8.5 fold increase. Follow-up DNA samples from 3 of the 4 subjects were analyzed for underlying DNA mutations using probe StB12.3 which detects insertions and methylation status of the FMR-1 gene. All 3 showed an affected female genotype with a large insert (greater than 500bp) and complete CpG island methylation. We conclude: (1) prenatally detected cytogenetic frequencies of females increase by an average 8.5 fold on follow-up postnatal studies, (2) genetic counseling should indicate the risks to be affected are approximately 75% when a positive female is prenatally detected, (3) DNA testing can help determine carrier status but may not accurately predict whether a female will be mentally affected. PMID- 1605242 TI - Hypothalamic-pituitary-gonadal function in two infants with Smith-Lemli-Opitz syndrome. AB - We report on the hypothalamic-pituitary-gonadal function in 2 male infants with the Smith-Lemli-Opitz (SLO or RSH) syndrome. Both infants had abnormal external genitalia. Basal and LHRH stimulated plasma gonadotropins were normal for age (1 month). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were normal for age and sex. Some forms of congenital adrenal hyperplasia (17,20 desmolase deficiency, 17 alpha-hydroxylase deficiency, and 3 beta-hydroxysteroid dehydrogenase deficiency) were ruled out by hormonal studies. The endocrinological findings indicate a normal hypothalamic-pituitary-gonadal function and a normal adrenal steroid biosynthesis in these 2 patients. A partial androgen receptor defect causing the genital malformations seems possible in one patient. Whether 5 alpha-reductase deficiency is the cause of the male pseudohermaphroditism in SLO syndrome remains the subject of future studies. PMID- 1605243 TI - Skeletal dysplasia, intracerebral calcifications, optic atrophy, hearing impairment, and mental retardation: nosology of dysosteosclerosis. AB - A girl who presented at 3 months of life with severe developmental delay, blindness, and hearing impairment was found to have intracerebral calcifications. Skeletal films showed craniotubular bone modeling consistent with dysosteosclerosis. The nosology of this disorder is discussed. PMID- 1605244 TI - Incidence and associations of single umbilical artery in prenatally diagnosed malformed, midtrimester fetuses: a review of 62 cases. AB - The absence of one umbilical artery (SUA) is the most common malformation of the umbilical cord. It may accompany other abnormalities or occur as an isolated defect. We examined 885 fetuses, terminated following the prenatal diagnosis of serious or lethal malformations between April 1977 and March 1989, for the presence of SUA. We found 62 cases of SUA. This represents an incidence of 7.01% (62/885). The most common abnormalities found in association with SUA were: (1) multiple malformations (8/11 cases, SUA incidence = 72.7%), (2) ADAM complex (7/14 cases, SUA incidence = 50.%), (3) multicystic renal dysplasia (5/20 cases, SUA incidence = 25.%), and (4) Potter sequence (5/21 cases, SUA incidence = 23.8%). These associations have not been documented previously. In 6 fetuses the Meckel syndrome was diagnosed, and SUA was present in 2 of these. Therefore, SUA may represent an additional anomaly in Meckel syndrome that has not been reported previously. PMID- 1605245 TI - Recognizable behavioral and somatic phenotype in patients with proximal interstitial 18q deletion: report on a new affected child and follow-up on the original reported familial cases. AB - We describe a moderately retarded boy with a chromosome 18 deletion involving the regions q11.2q12.2. His phenotype is similar to that of other reported cases of proximal interstitial deletions involving 18q. We also provide follow-up information on the first 4 cases of proximal interstitial deletion of 18q from a family with a complex chromosome rearrangement originally reported in 1974. PMID- 1605246 TI - Restrictive dermopathy, a lethal form of arthrogryposis multiplex with skin and bone dysplasias: three new cases and review of the literature. AB - Restrictive dermopathy is a rare, lethal autosomal recessive syndrome. We report on 3 unrelated affected stillborn infants of consanguineous parents. Clinical findings include a tight, thin, translucent, taut skin, which tears spontaneously in flexion creases, arthrogryposis multiplex congenita (including the temporomandibular joint), enlarged fontanelles, typical face and dysplasia of clavicles and long bones. Histologic abnormalities include hyperplastic, abnormally keratinized epidermis, reduced tonofilaments, thin, compact dermis with hypoplasia of the elastic fibres, and abnormal subcutaneous fat. Fifteen previous cases are reviewed. PMID- 1605247 TI - Autosomal dominant polycystic kidney disease: new information for genetic counselling. AB - We evaluated the accuracy of ultrasonographic diagnosis of autosomal dominant polycystic kidney disease (ADPKD) and factors influencing its prognosis in members of 17 Newfoundland families originally described in 1984. In 10 families showing genetic linkage between ADPKD and markers for the PKD1 locus, rates of false negative ultrasonographic diagnosis are estimated as 36% below the age of 10 years and 8% or less thereafter, comparable with findings of genetic linkage studies of a subset of family members. At ages above 30 years, false negative ultrasonographic diagnosis of PKD1 disease is unlikely. In 2 families in which ADPKD is not co-inherited with PKD1 markers, only 11% of members aged less than 30 years had kidney cysts. The mean (SE) age of onset of ESRD is 56.3 (1.8) years for persons with the PKD1 form of ADPKD, and 68.7 (1.7) years for affected members of families in which ADPKD is not co-inherited with PKD1 markers (P = 0.01). In the PKD1 families, age of onset of end stage renal disease (ESRD) was unrelated to the sex of the affected individual but was earlier in persons inheriting the disease from their mothers than from their fathers (50.5 vs. 64.8 years, P = 0.004), consistent with an influence of genetic imprinting on disease progression. In females with a PKD1 mutation, onset of ESRD was not influenced by parity. In PKD1 families, resemblance in age of onset of ESRD was apparent; variation was less within than between families (F = 13.0, P less than 0.0001), and risk of false negative ultrasonographic diagnosis appears largely restricted to families in which ESRD occurs relatively late. PMID- 1605248 TI - Molecular and cytogenetic investigation of complex tissue-specific duplication and loss of chromosome 21 in a child with a monosomy 21 phenotype. AB - Several recent molecular studies have suggested that the clinical phenotype of Down syndrome may be due to triplication of 21q22 [McCormick et al., 1989] as initially suggested by Niebuhr [1974], and perhaps just 21q22.2 [Korenberg et al., 1989, 1990; Rahmani et al., 1989]. Recently, we studied a patient with a phenotype inconsistent with Down syndrome, whose lymphocyte karyotype on several occasions detected only 46,XX,-21, + dic(21)(qter----p11::p11----qter). Combined karyotype and molecular studies on both lymphocytes and fibroblasts allowed correct identification of the abnormality as a complex monosomy/trisomy 21 mosaicism involving a marker derived from idic (21) (p11), and probable assignment of a maternal origin for the error(s). The patient's phenotype was found to be most consistent with monosomy 21. Detailed study of our patient underscores (1) the need for confirmation that there is phenotype/karyotype correlation and (2) the usefulness of molecular analyses to complement the cytogenetic interpretation of marker chromosomes. PMID- 1605249 TI - Interstitial deletion of chromosome 16q: 16q22 is critical for 16q- syndrome. AB - Partial deletion of 16q is rare; to our knowledge only 12 cases have been published. Fryns et al. [Hum Genet 38:343-346, 1977] described the first of these cases and proposed a new clinical entity. Our patient was a girl and had many minor anomalies of the kind often observed in 16q- syndrome. Severe failure to thrive due to emesis and diarrhea were also observed. High resolution banding methods showed that the chromosome constitution of the patient was 46,XX,del(16)(q22.1q22.3). This suggests that 16q22 is critical for the syndrome. PMID- 1605250 TI - Mental retardation, microbrachycephaly, hypotelorism, palpebral ptosis, thin/long face, cleft lip, and lumbosacral/pelvic anomalies. AB - We describe 2 Brazilian sisters with a combination of clinical signs strongly suggesting a new autosomal recessive MCA/MR syndrome. PMID- 1605251 TI - Ring chromosome 20 and possible assignment of the structural gene encoding human carboxypeptidase-L to the distal segment of the long arm of chromosome 20. AB - We report on a 14-year-old boy with ring chromosome 20. Clinical manifestations included postnatal growth retardation, epilepsy, microcephaly, behaviour disorder, minor facial anomalies, small sella turcica, possible partial growth hormone deficiency, and mental retardation. A decreased activity of enzyme carboxypeptidase-L/protective protein (CP/PP) in cultured fibroblasts was demonstrated in our patient and a patient with a karyotype 46,XY,-14, + der(14)t(14;20)(14pter----14q32.3::20q13.1----20qter)m at. This suggests possible assignment of the CP/PP gene to the distal segment of 20q. PMID- 1605252 TI - Molecular genetic and immunological analysis of dystrophin of a young patient with X-linked muscular dystrophy. AB - We examined the nucleotide sequence of deleted part of dystrophin mRNA and its translational product with immunoblot and immunohistochemical methods in a 6-year old boy with a deleted DMD/BMD gene. On Southern blot analysis of his genomic DNA, we found a deletion of exons 10 to 37 in the DMD/BMD gene, which was expected to preserve the translational open reading frame (ORF). Dystrophin mRNA from his biopsy sample was amplified by polymerase chain reaction (PCR) and sequenced. The mRNA lacked the sequence corresponding to the gene from exons 10 37, and the translational ORF was preserved. The transcript was expected to code a 260 kDa protein. Dystrophin expressed in this patient was investigated with immunological methods. A 260 kDa protein was detected by immunoblot analysis with antidystrophin antiserum against nondeleted regions. These observations confirmed the preservation of the reading frame and the 260 kDa protein was produced as a mutant dystrophin. All these are compatible with the diagnosis of BMD. However, the immunohistochemical pattern of his muscle cells was peculiar. With deleted region-directed antiserum, the membrane was not stained at all as in DMD patients. In contrast, with nondeleted-region-directed antiserum, all the muscle cell membrane was stained continuously as in non-DMD/BMD individuals. These are quite different from the staining pattern in most BMD patients where muscles are stained patchily or discontinuously. PMID- 1605253 TI - Transmission of the fra(X) haplotype from three nonpenetrant brothers to their affected grandsons. AB - We report on a family showing transmission of the fra(X) gene by 3 nonpenetrant, fra(X) negative, normally intelligent, full and half-brothers to their affected grandsons. The mothers of the affected boys are obligate carriers, fra(X) negative, and of normal intelligence. This family illustrates the "Sherman Paradox" and is compatible with the predictions of the Laird X-inactivation imprinting model. In addition, molecular and/or cytogenetic studies have enabled at-risk relatives to learn more about their carrier fra(X) status and have allowed for more accurate genetic counselling. PMID- 1605254 TI - Recurrence of extrahepatic biliary atresia in two half sibs. AB - Extrahepatic biliary atresia (EHBA) usually is a sporadic disorder. Familial cases, including occurrence in sibs and twins, have been reported. We report the first recurrence of EHBA in two half sibs born to a common father and unrelated mothers and suggest the possibility of gonadal mosaicism for a new dominant mutation. PMID- 1605255 TI - Opitz (BBB/G) syndrome: oral manifestations. AB - We studied a new case of the G (Opitz BBB/G) syndrome in a 12-year-old boy. Several relatives had partial manifestations of the disorder. A comprehensive dental evaluation of the propositus was conducted; included is, to our knowledge, the first published cephalometric analysis of a G syndrome patient. We reviewed 139 cases of the G syndrome; 48 of them had at least one oral abnormality. These included clefting, micrognathia, ankyloglossia, and high-arched palate. Male G syndrome patients are more likely to have oral anomalies than affected females. PMID- 1605256 TI - Neu-Laxova syndrome: prenatal ultrasonographic diagnosis, clinical and pathological studies, and new manifestations. AB - A diagnosis of the Neu-Laxova syndrome (NLS) was made by ultrasonography at 32 wks of gestation. Ultrasonographic examination showed intrauterine growth retardation (IUGR), Dandy-Walker anomaly, choroid plexus cysts, receding forehead and microcephaly, bilateral cataract without prominent eyes, scalp edema with no generalized edema, retrognathia, curved penis, and flexion deformities of limbs. The findings in this case are consistent with NLS; however, they did not fit any of Curry's [1982] groups. Massive swelling of hands and feet were among the main manifestations in classic NLS cases. In the case presented herein, edema was noted only in the scalp. This might shed further light on the question of variability vs. heterogeneity in the NLS. This case shows the existing possibility of an early diagnosis of NLS and adds Dandy-Walker anomaly and choroid plexus cysts as new findings to this syndrome. PMID- 1605257 TI - Completeness of catalogs of autosomal dominant, autosomal recessive, and X-linked phenotypes. AB - The completeness of McKusick's catalogs of Mendelian Inheritance in Man (MIM) as to the number of phenotypes included was studied by estimating the degree of concordance with the Dutch Gene Catalog of the Department of Medical Genetics of the University of Groningen, The Netherlands. On a total of 355 Mendelian phenotypes described in persons living in The Netherlands or originating from this country, there were nine disease entities which were not present in MIM. As judged from this comparison MIM attains 97.5% completeness (95% CI: 95.3-98.7%). Similar comparisons with data from other countries are needed before a final conclusion can be reached. Corresponding contributors in different countries or linguistic areas might further improve MIM's completeness. PMID- 1605258 TI - Additional case of Neuhauser megalocornea and mental retardation syndrome with congenital hypotonia. AB - We report on a 3-1/2-year-old Spanish girl with the Neuhauser megalocornea and mental retardation syndrome. A review shows that megalocornea, mental retardation, and, presumably, hypotonia, are the major manifestations for diagnosis. The facial appearance of the typical cases is characterised by frontal bossing, broad nasal bridge, mild hypertelorism, long upper lip, and small mandible. PMID- 1605259 TI - Apparent cleidocranial dysplasia associated with abnormalities of 8q22 in three individuals. AB - Cleidocranial dysplasia is an autosomal dominant, generalised skeletal disorder characterised by variable clavicular hypoplasia, frontal bossing, multiple Wormian bones, and delayed eruption of the teeth. The gene locus for this syndrome has not yet been assigned. Three individuals with manifestations of cleidocranial dysplasia associated with rearrangements of chromosome 8q22 are described. The evidence presented suggests that the gene for cleidocranial dysplasia may be located on chromosome 8q in humans in a region showing homology to mouse chromosome 3. PMID- 1605260 TI - Vascular abnormalities at the site of limb deficiency. AB - A case is presented of a child born with a left forearm deficiency and a cavernous hemangioma covering the tip of the forearm and left elbow. Points relative to the potential associations of vascular abnormalities and limb deficiencies are discussed. PMID- 1605261 TI - Trisomy 16p in a liveborn offspring due to maternal translocation t(16;21)(q11;p11) and review of the literature. AB - We report on a case of dup(16p) and review previous cases. The triplicated chromosome region leading to this specific syndrome lies in 16p13.1 p13.3. Most of the cases are inherited and the mode of segregation was found to be 3:1 in half of the cases, but these observations might be due to biases. The other chromosomes involved in the translocations as well as the breakpoints in these chromosomes do not appear to be random. PMID- 1605262 TI - Lujan syndrome in a Mexican boy. PMID- 1605263 TI - Microcephalic osteodysplastic primordial dwarfism and cephalo-skeletal dysplasia (Taybi-Linder syndrome) PMID- 1605264 TI - Tetra-phocomelia with multiple malformations: X-linked amelia, or Roberts syndrome, or DK-phocomelia syndrome? PMID- 1605265 TI - Pseudotrisomy 13 syndrome. PMID- 1605266 TI - Familial posterior helical ear pits. PMID- 1605267 TI - Familial atrial septal defect with prolonged atrioventricular conduction. PMID- 1605268 TI - Pallister-Hall syndrome associated with an unbalanced chromosome translocation. AB - We report 3 cases of Pallister-Hall syndrome involving hypothalamic hamartoblastoma, hypopituitarism, cranial, and limb abnormalities. The first 2 cases represent the first apparent sibs reported with this syndrome. Patient 1 represents the first known patient with this syndrome with an abnormal karyotype. PMID- 1605269 TI - Are we ready to answer? PMID- 1605270 TI - HIV and cervical neoplasia: if you see one, look for the other. PMID- 1605271 TI - Case example: valvular dehiscence. PMID- 1605272 TI - Who's in charge here? PMID- 1605273 TI - A question of support. PMID- 1605274 TI - A question of support. PMID- 1605275 TI - The power of nursing. PMID- 1605276 TI - Misbegotten pride? PMID- 1605277 TI - Adjusting the beat. PMID- 1605278 TI - Dialogues with excellence: bringing Stanley back. PMID- 1605279 TI - Rapid neuro assessment. PMID- 1605280 TI - How to boost the odds of a painless i.v. start. PMID- 1605281 TI - Helping America take its medicine. PMID- 1605282 TI - Tips for delegating to the right person. PMID- 1605283 TI - 'Wait' is a four-letter word. PMID- 1605284 TI - The safety of oral contraceptives: epidemiologic insights from the first 30 years. AB - Because oral contraceptives are used by tens of millions of healthy women, their safety for short-term and long-term use is an important issue that has been examined in a large number of epidemiologic studies. These studies have become more rigorous and have increased in size and analytic sophistication over the years. Although breast cancer remains the most important safety concern, the bulk of recent data suggests that oral contraceptives have no overall impact on a woman's risk of developing this disease. The results are less clear on the risk of cervical cancer and its precursors because of methodologic problems. However, the newer oral contraceptive formulations no longer appear to be associated with an increased risk of myocardial infarction or stroke. PMID- 1605285 TI - Clinical and metabolic considerations of long-term oral contraceptive use. AB - Newer lower dose formulations are associated with an improved cardiovascular disease risk marker profile, which supports their use for longer periods and among older women. Epidemiologic studies of the newer formulations are limited. Without clinical information, an evaluation of the effects of more recent formulations on metabolic risk markers for cardiovascular disease is useful. In a large cross-sectional study, a reduction in the progestin dose and use of alternative progestins substantially reduced the proportion of oral contraceptive users with values associated with an increased risk of cardiovascular disease. No progression in metabolic changes was found by analyzing the effect of the duration of oral contraceptive use. The user's age interacted positively with the oral contraceptive--induced increase in serum triglyceride levels, but there was no interaction of age with the oral contraceptive's effect on oral glucose tolerance, glucose and insulin responses, low-density lipoprotein cholesterol, or high-density lipoprotein subfraction 2 cholesterol levels. PMID- 1605286 TI - The efficacy and tolerability of norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol): results of an open, multicenter study of 59,701 women. AB - The efficacy and tolerability of a new oral contraceptive, norgestimate/ethinyl estradiol (250 micrograms of norgestimate/35 micrograms of ethinyl estradiol; Cilag GmbH Research, Sulzbach, Germany) were examined in an open-label study of 59,701 women who were evaluated during 342,348 menstrual cycles; 42,022 women completed the planned treatment regimen of six cycles. A use-efficacy (overall) Pearl index of 0.25 pregnancies per 100 woman-years was calculated based on 342,348 cycles. Tolerability was assessed for all women who completed six treatment cycles. Reductions in mean cycle length and duration of bleeding were noted; 32% of the women experienced reductions in the intensity of bleeding by the end of cycle 6. After six cycles of use, amenorrhea occurred in 1%, spotting in 4%, and breakthrough bleeding in 3% of the participating women. Treatment with norgestimate/ethinyl estradiol had minimal effects on weight, blood pressure, pulse, lipid metabolism, and blood glucose. Adverse effects (acne, nausea, or headaches) occurred at low frequencies and in many cases, were reduced compared with pretreatment levels. The results of this large-scale open trial were comparable with results from two other multicenter trials of the same formulation. PMID- 1605287 TI - Norgestimate: a clinical overview of a new progestin. AB - The efficacy and safety of a new monophasic oral contraceptive, norgestimate/ethinyl estradiol, containing the third-generation progestin, norgestimate (250 micrograms), and ethinyl estradiol (35 micrograms), are reviewed. Norgestimate/ethinyl estradiol demonstrates excellent contraceptive efficacy, with a Pearl index of 0.25. Cycle control is reliable, with a low incidence of breakthrough bleeding and spotting. Because of the minimal androgenicity of norgestimate, norgestimate/ethinyl estradiol has a low impact on carbohydrate and lipid metabolism. It neither reduces the vasodilatory and antiaggregatory prostacyclin nor increases its endogenous antagonist, thromboxane. Norgestimate/ethinyl estradiol has no significant effect on blood coagulation factors. All these characteristics suggest that norgestimate/ethinyl estradiol may be associated with a lower risk of cardiovascular disease than other oral contraceptives currently available. Epidemiologic data, however, are not available, and physicians should be reluctant to prescribe it or any oral contraceptive to patients who have a history of vascular or thrombotic disorders. PMID- 1605288 TI - Introduction to steroids in the menopause. AB - Menopausal symptoms and signs associated with the reduction of ovarian function include an increased incidence of cardiovascular disease and loss of bone mass as well as less serious but more uncomfortable symptoms such as vasomotor flushes and atrophy of the vaginal wall. Although unopposed estrogen effectively reverses these and other menopausal symptoms, it is well established that without the addition of progestin there is an unacceptably high risk of developing hyperplasia or cancer of the endometrium. Depending on the type and dose of progestin added, however, this addition may reverse estrogen's beneficial cardiovascular effects and produce unwanted side effects. Lower doses and newer progestins, such as norgestimate, gestodene, and desogestrel, have demonstrated a decreased potential to reverse the positive cardiovascular effects of estrogen while still eradicating persisting or de novo endometrial hyperplasia. PMID- 1605289 TI - The benefits and risks of hormone replacement therapy: an epidemiologic overview. AB - In postmenopausal women estrogens alone are effective in reversing vasomotor symptoms and vaginal atrophy. They also prevent the bone loss associated with osteoporosis and reduce the risk of cardiovascular disease, probably through their beneficial effects on lipid metabolism. Unopposed long-term estrogen therapy, however, increases the risk of developing endometrial hyperplasia, endometrial cancer, and possibly breast cancer as well. The risk of developing endometrial cancer can be reduced by combining a progestin with the estrogen, by controlling obesity, and by rigorous clinical screening and surveillance. The effect of progestins on the risk of developing breast cancer is still controversial. Although some progestins may reverse the cardioprotective effect of estrogens, those with minimal androgenicity appear less likely to do so. Hormone replacement therapy that combines estrogen with a progestin of minimal androgenicity is thus a rational alternative to unopposed estrogen therapy. Current epidemiologic knowledge suggests that the benefits of hormone replacement therapy, with or without any progestins, strongly outweigh the risks. PMID- 1605290 TI - The effect of sex steroids on the skeleton in premenopausal women. AB - Whereas peak bone mass is genetically determined, the skeletal growth, maturation, and maintenance required to reach this peak may be influenced by physical activity, ovarian function, and nutrition. Estrogen deficiency at menopause leads to increased skeletal remodeling and loss of bone mass, which can result in osteoporotic fractures. Entering menopause with low bone mass is a risk factor itself, because bone mass predicts future risk of fracture. The administration of exogenous steroids can reverse the setting of the "mechanostat" to lower levels after ovarian dysfunction, although it is unclear whether oral contraceptives can modify bone mass in the ovulatory premenopausal woman. Our recent data suggest that the use of steroidal hormones to treat menstrual irregularity (presumably relative to ovarian dysfunction), as opposed to fertility control, is more likely to positively affect bone mass. It is even less clear whether hyperestrogenic states (e.g., pregnancy) affect the skeleton. Recent evidence from bone mass changes that occur in women with ovulatory cycles and inadequate luteal phase function suggests that progestins may also influence skeletal metabolism. PMID- 1605291 TI - The role of progestins in hormone replacement therapy. AB - Long-term estrogen replacement therapy prevents osteoporosis and reduces the risk of cardiovascular disease in postmenopausal women. Progestins are used to prevent endometrial hyperplasia and carcinoma but should not be prescribed for women who have had hysterectomies. Doses that decrease mitotic activity are sufficient. Recent data suggest that a continuous combined regimen of estrogen and progestin may increase bone mass in women who have established osteoporosis. Some progestins may oppose the beneficial effects of estrogen on the cardiovascular system in some women. Critical cardiovascular effects of progestins include a reduction in the serum level of high-density lipoprotein cholesterol and a direct effect on arterial tone, which may be mediated by an attenuation of prostacyclin production and other factors. Therefore it is prudent to prescribe the lowest effective dose of a progestin that demonstrates the least metabolic impact. The dose and type of progestin should be balanced with the estrogen component so that the estrogen-dominant metabolic effects prevail. With this approach the difference in mortality rates between women who use unopposed estrogen and women who use estrogen-progestin therapy will be minimized and will make the appropriate sequential addition of progestin an option in postmenopausal hormone replacement therapy. PMID- 1605292 TI - Use of two types of estradiol-releasing skin patches for menopausal patients in a tropical climate. AB - As part of a program to evaluate nonoral routes for delivery of estrogen replacement therapy at the National University Hospital, Singapore, we assessed two different 50 micrograms estradiol patches. The first study (patch A) was terminated because of a high rate of skin reactions. Tests of the components of this patch identified the alcohol carrier as the cause of these reactions when combined with an occlusive membrane in the tropical Singapore climate. A subsequent clinical trial with 21 female subjects was undertaken with a different 50 micrograms estradiol patch (patch B). Twenty patients completed the 6-month study. Patch B was as effective as patch A, caused fewer skin reactions, and adhered better. PMID- 1605293 TI - Autistic disorder: a neuropsychological enigma. AB - Autism is increasingly viewed as an expression of an unidentified neurological disorder. Because understanding of neurological dysfunction is basic to evaluation and treatment in occupational therapy, this article provides a comprehensive and critical review of the literature since 1985 concerning the neuropsychology of autistic disorder. The research is categorized into four basic types: (a) neuropsychological testing of functional abilities, (b) treatment studies based on neuropsychological hypotheses, (c) autistic-related diseases and genetic disorders, and (d) neuroanatomical and neurophysiological studies. The research shows a spectrum of neurological impairments within the brain stem, cerebellum, midbrain, and frontal lobe. These impairments are associated with deficits in socioemotional skills, sensory processing, motor planning, and cognitive flexibility. This research suggests that persons with autistic disorder need evaluation and treatment of a wide spectrum of functional deficits. PMID- 1605294 TI - Upper extremity functional changes following selective posterior rhizotomy in children with cerebral palsy. AB - Spasticity in children with cerebral palsy may inhibit function and reduce progress in therapy. Selective posterior rhizotomy, a neurosurgical procedure, has been found to effectively reduce spasticity in selected cases. The literature suggests that positive changes in upper extremity function results from this surgery. At the Alberta Children's Hospital in Calgary, Alberta, Canada, all candidates for this surgery are screened by the neuromotor clinic team, which includes an occupational therapist, a speech therapist, and a physical therapist. This paper outlines the specific changes seen in the upper extremity functions of 7 children over a 12-month period following their surgeries. The data collected suggest the children had improved function in activities of daily living, play skills, balance, and endurance. This paper focuses on the changes in activities of daily living and recommends future direction for research in this area. PMID- 1605295 TI - The relationship between elbow position and grip strength. AB - Forty-six graduate students participated in a study to investigate the effect of elbow position on grip-strength measurements. Sixteen males and 30 females, aged 21 to 46 years, participated in the study. Data collection procedures followed standardized grip-strength testing guidelines established by the American Society of Hand Therapists, with the exception of elbow position. Grip-strength measurements were taken with the elbow positioned at 0 degree, 45 degrees, 90 degrees, and 135 degrees of flexion. The results showed a significantly stronger grip-strength measurement at 0 degree of flexion and the weakest grip-strength measurement at 135 degrees of flexion. This study supports the use of a standardized method for hand-strength testing. The knowledge that grip-strength measurement is highest when the elbow is fully extended could affect treatment planning. PMID- 1605296 TI - Application of the Allen Cognitive Level Test in assessing cognitive level functioning of emotionally disturbed boys. AB - The purpose of this study was to ascertain the applicability of the Allen Cognitive Level Test (ACL) (Allen, 1982, 1985), developed for use with adult psychiatric patients, to emotionally disturbed children aged 8 to 15 years. The subjects' performance on the ACL was compared with their performance on two other instruments that measure features of cognition: the Developmental Test of Visual Motor Integration (VMI) (Beery & Buktenica, 1982) and the Perceptual Memory Task (McCarron, 1984). Pearson product-moment correlations were computed to study the relationships of the ACL, the Perceptual Memory Task full-scale and subscale scores, and the VMI raw and age-equivalent scores. The Perceptual Memory Task scores showed little or no correlation with the ACL scores. Correlations of the ACL with the VMI scores revealed moderate but significant coefficients. A relationship between age and ACL score was found. Preliminary data would indicate that the ability of emotionally disturbed children to function in the school environment depends on their mastery of task demands and that occupational therapy intervention cannot be based solely on age or level of intelligence. PMID- 1605297 TI - Reasons for choosing occupational therapy as a profession: implications for recruitment. AB - This study examines the ways in which 272 recently certified occupational therapists learned of the profession of occupational therapy and the factors that influenced their decisions to choose occupational therapy as a career. The data were analyzed according to age, sex, and geographic region to identify potential ways to improve recruitment efforts. The results indicated that therapists most often learned of the profession while working in a health care setting. First exposure to occupational therapy was usually through an acquaintance in the profession, a family member, or a friend. The primary reasons for choosing occupational therapy included a desire to help people with disabilities, the promise of challenge and variety, the opportunity to work in a health care setting, and the belief that jobs are plentiful. The factors most likely to dissuade people from the profession were the expense of an education and lack of a clear understanding of occupational therapy. PMID- 1605298 TI - Socialization groups: using The Book of Questions as a catalyst for interaction. AB - This article describes the use of The Book of Questions (Stock, 1987) as a tool for assessment and as a catalyst for social interaction in an acute short-term inpatient psychiatric unit. Examples of questions and how they can be used to provide information for the evaluation of personality style and social and interpersonal skills are provided. Group objectives, membership criteria and format, and leadership techniques are discussed. Analysis of the group activity and patients' responses to the group indicates that a group structured around The Book of Questions facilitates social interaction and is easily transferable to social activities outside of the structured therapeutic group setting and hospital environment. PMID- 1605299 TI - The effects of deep pressure on self-stimulating behaviors in a child with autism and other disabilities. PMID- 1605300 TI - A thermoplastic thumb post for the treatment of thumb-sucking. PMID- 1605301 TI - The challenge of providing occupational therapy in mental health. AB - Although the number of occupational therapists working in mental health has dwindled, the number of people who need our services has not. In our tendency to cling to a medical model of service provision, we have allowed the scope and content of our services to be limited to what has been supported within this model. A social model that stresses functional adaptation within the community, exemplified in psychosocial rehabilitation, offers a promising alternative. A strongly proactive stance is needed if occupational therapists are to participate fully. Occupational therapy can survive without mental health specialists, but a large and deserving population could ultimately be deprived of a valuable service. PMID- 1605302 TI - Supporting consumer-mandated programming for persons with developmental disabilities. AB - The development of health policies is often initiated to meet political objectives, but policies can be, to a great extent, shaped by information found in surveys and other health services research. The following article provides an example of how survey data can be used to shape policy regarding developmental disabilities. It also illustrates how occupational therapists can use the data to adjust the focus of their services to meet consumer demand and implement shifts in policy. PMID- 1605303 TI - Against use of physical agent modalities. PMID- 1605304 TI - Rabbi Hirsch influenced the Chicago School of Civics and Philanthropy. PMID- 1605305 TI - Stromelysin and tissue inhibitor of metalloproteinases gene expression in rheumatoid arthritis synovium. AB - In situ hybridization was used to localize stromelysin mRNA in rheumatoid arthritis synovial tissue. Stromelysin antisense probes hybridized primarily to the intimal lining layer in frozen tissue sections, with little or no sublining signal. The expression of stromelysin correlated with cellularity as determined by hybridization with an actin probe. Double-label experiments were performed to detect tissue inhibitor of metalloproteinases (TIMP) and stromelysin mRNA simultaneously in synovial tissue. Coexpression of both mRNA species was identified in a subpopulation of intimal lining cells. In some highly inflammatory tissues, virtually all of the lining cells hybridized to both probes. However, in other tissues, expression of the two genes was discordant, with large numbers of TIMPpositive/stromelysin(negative) cells. Similar results were observed with late-passage cultured synoviocytes. Unstimulated cells did not express the stromelysin gene, whereas TIMP was constitutively produced. Addition of interleukin-1 beta (IL-1 beta) or tumor necrosis factor-alpha (TNF-alpha) to cultures induced the former but had little effect on the latter. Double-label experiments clearly showed discordant expression in individual cells. Stromelysin and TIMP genes likely have distinct transcriptional controls that provide precise control over the local environment and matrix turnover. PMID- 1605306 TI - Expression and cell distribution of the intercellular adhesion molecule, vascular cell adhesion molecule, endothelial leukocyte adhesion molecule, and endothelial cell adhesion molecule (CD31) in reactive human lymph nodes and in Hodgkin's disease. AB - The immunocytochemical expression of intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule (VCAM-1), endothelial leukocyte adhesion molecule (ELAM-1), endothelial cell adhesion molecule (EndoCAM CD31), and HLA-DR antigens was investigated in sections of 24 reactive lymph nodes and in 15 cases of Hodgkin's disease. ICAM-1 was detected in sinus macrophages, follicular dendritic reticulum cells (FDRCs), interdigitating reticulum cells (IDRCs), epithelioid macrophages, Hodgkin's cells (HCs), and vascular endothelium. ICAM-1 expression was often associated with that of HLA-DR antigens. VCAM-1 was detected in FDRCs, in fibroblast reticulum cells (FRCs), in macrophages, and in rare blood vessels. EndoCAM (CD31) was constitutively expressed in all types of endothelial cells, sinus macrophages, and in epithelioid granulomas. ELAM-1 was selectively expressed by activated endothelial cells of high endothelium venules (HEVs). When expression of the inducible adhesion molecules ICAM-1, VCAM-1 and ELAM-1 was comparatively evaluated in HEVs, it was found that ICAM-1 + HEVs were present in all reactive and HD nodes, whereas ELAM-1 and/or VCAM-1 were expressed only in those pathologic conditions characterized by high levels of interleukin-1/tumor necrosis factor (IL-1/TNF) production, such as granulomatosis and Hodgkin's disease. In Hodgkin's disease, the expression of ELAM-1/VCAM-1 was more pronounced in cases of nodular sclerosis and was associated with a significantly higher content of perivascular neutrophils. PMID- 1605307 TI - Adrenal medullary tumors and iris proliferation in a transgenic mouse model of neurofibromatosis. AB - The expression of the human T-cell lymphotropic virus type 1 (HTLV-1) tax gene in transgenic mice has been shown to result in the development of neurofibromas. Further characterization of these transgenic mice has revealed other significant pathologic similarities between this transgenic mouse model and human neurofibromatosis (NF). Pheochromocytomas of the adrenal medulla and hamartomas of the iris are well-recognized manifestations of human NF. Adrenal medullary tumors have been found in 68% of transgenic animals that were studied. They appear, however, not to be pheochromocytomas, but rather composed of undifferentiated spindle cells. Proliferation of fibroblastlike cells in the iris also occurs in one-half of the transgenic animals surviving more than 6 months. Melanocytes, however, have not been found in the transgenic iris lesion, although they are characteristically found in the Lisch nodules of human NF. The similarities between human neurofibromatosis and this transgenic mouse model (in which the overexpression of a single gene results in neoplasia) are discussed. This transgenic system may provide further insights into molecular mechanisms involved in the pathogenesis of neurofibromatosis. PMID- 1605308 TI - Local changes in proteoglycan synthesis during culture are different for normal and osteoarthritic cartilage. AB - Proteoglycan synthesis of mild-to-moderate osteoarthritic human knee cartilage was compared with that of normal cartilage of the same donor. Immediately after cartilage was obtained, the synthesis rate of proteoglycans was higher for osteoarthritic cartilage than for normal cartilage. Proteoglycan synthesis was then located, for both normal and osteoarthritic cartilage, in the middle and deep zone. However, after 4 days of culture, proteoglycan synthesis rate was higher for normal cartilage than for osteoarthritic cartilage. The reason for this transition from a lower to a higher proteoglycan synthesis rate was a strong increase in the proteoglycan synthesis in the superficial zone of normal cartilage. This was not observed for the osteoarthritic cartilage. The chondrocytes in the superficial zone of osteoarthritic cartilage, in contrast to normal cartilage, were mainly joined in cell clusters and proliferating. This may explain their inability to contribute to proteoglycan synthesis. PMID- 1605309 TI - Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction. AB - Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the periportal area. They could be classified into three types. Type I cells showed an oval cell shape and oval nucleus, early or established formation of junctional complexes with adjacent cells, a full assortment of cytoplasmic organelles, and bundles of tonofilaments. Type II cells showed features of bile-duct cell differentiation, including lateral interdigitations, apical microvilli, basal pinocytotic vacuoles, and basement membrane formation. In contrast, type III cells displayed additional features indicating hepatocellular differentiation, such as a more prominent nucleus, formation of a hemicanaliculus, and glycogen rosettes. It is concluded that these small cells of epithelial nature display variable differentiation characteristics of either bile-duct type cells or hepatocytes. These findings support the existence of bipotential progenitor epithelial cells in human liver. They may have implications for liver regeneration and carcinogenesis. PMID- 1605311 TI - Bovine leukocyte adhesion deficiency. Beta 2 integrin deficiency in young Holstein cattle. PMID- 1605312 TI - Diet and dental caries among later stone age inhabitants of the Cape Province, South Africa. AB - Stable carbon isotope measurements and incidences of dental caries are presented for three groups of prehistoric human skeletons from different regions of the Cape Province, South Africa. The isotopic analyses of bone collagen demonstrate the importance of marine foods in the diet and vary through time, across space, and according to sex. The incidence of dental caries ranges from 0% among heavily marine-dependent individuals from the south-western Cape coast, to 17.7% among skeletons from an archaeological site on the south coast. The extremely high incidence of caries in a hunter-gatherer population may be related to lack of fluoride in the water. PMID- 1605310 TI - Cationic immune complex arthritis in mice--a new model. Synergistic effect of complement and interleukin-1. AB - A novel cationic immune-complex-mediated arthritis (ICA) model was developed in mice. The highly cationic protein lysozyme was coupled to poly-L-lysine (PLL) and injected intra-articularly into the knee joint of the mouse, shortly after systemic administration of specific antibodies. A vehement joint inflammation developed, characterized by severe joint swelling and the influx of predominantly polymorphonuclear (PMN) leukocyte. Unique properties were combined in this protein. First, an excellent retention of the antigen in joint structures was found, facilitating sufficient IC formation in the synovial tissue and at the cartilage surface. Secondly, PLL.lysozyme appeared to be a potent inducer of interleukin-1 (IL-1). Similar IL-1 production was measured at 6 hours, in both immune or nonimmune mice. Neutralization with antibodies against either IL-1 alpha or IL-1 beta revealed that IL-1 alpha was the dominant cytokine. Resident cells were responsible for this IL-1 production since a comparable IL-1 signal was measured after intra-articular injection of PLL.lys in neutropenic mice. We further investigated whether IL-1 and complement factors were involved in the onset of this ICA. Neutralizing the IL-1 production with antibodies directed against IL-1 alpha and beta showed a significant decrease in joint swelling. Complement depletion by cobra venom factor also prevented the onset of arthritis for the greater part. Only a minor swelling remained at 6 hours after eliciting arthritis, which was similar to the swelling after injecting the antigen alone and probably reflects IL-1 mediated inflammation. In this study, the authors show a synergistic action of IL-1 and complement in the onset of cationic ICA. Unique properties of the antigen such as excellent retention and its ability to induce IL-1 are combined within one molecule and make this antigen arthritogenic in the presence of antibodies and complement activation. PMID- 1605313 TI - Maxillary canine/third premolar transposition in a prehistoric population from Santa Cruz Island, California. AB - Canine/premolar transposition is rare in both historic and prehistoric Homo sapiens with a known occurrence of less than 0.10%. This report describes a prehistoric population sample from one site (SCrI-3) on Santa Cruz Island, California in which the rate of C/P3 transposition is greater than eight percent, based on nine of 106 adult crania which exhibit the anomaly either uni- or bilaterally. As a means of investigating the etiology of this anomaly, the location of the canine root in adult crania was studied. Root location should indicate tooth bud origin, a factor likely to be under genetic control. In crania with normally erupted canines, the superior portion of the root averages 4.43 mm from alare, while this distance is 8.96 mm for anomalous roots. This difference suggests that during ontogeny the tooth buds for the canine and premolar arose in the wrong (or reversed) places, causing the teeth to erupt anomalously. It is suggested that inbreeding in a small island community resulted in a short-lived appearance of this anomaly at a high frequency. PMID- 1605314 TI - Palatine torus in the Greenlandic Norse. AB - Physical anthropologists have long been intrigued by the distinctive oral tori expressed by the medieval Norse populations of Iceland and Greenland. To assess the temporal and spatial variation of one form of oral tori, palatine torus, observations were made on all available Greenlandic Norse skeletons, as well as on samples of medieval Icelanders and Norwegians. In terms of temporal variation, 12th to 14th century (medieval) Greenlanders from the Eastern and Western settlements exhibited higher frequencies and more pronounced expressions of palatine torus compared with early 11th century Greenlanders. The early Greenlandic sample closely approximated the medieval Icelandic and Norwegian samples for total torus frequency, although the Norwegians exhibited the trait to a less pronounced degree. As degree of expression is the most distinctive aspect of torus variation among the Norse, some combination of environmental factors, including increased masticatory stress and chronic undernutrition, probably accounts for most of the difference between settlement period and medieval Greenlanders. Although palatine torus may be hereditary in part, environmental factors play a significant role in the expression of this trait. PMID- 1605315 TI - Dental and cranial affinities among populations of east Asia and the Pacific: the basic populations in east Asia, IV. AB - The origins of the four major geographical groups recognized as Australomelanesians, Micronesians, Polynesians, and East and Southeast Asians are still far from obvious. The earliest arrivals in Sahulland may have migrated from Sundaland about 40,000-50,000 years B.P. and begun the Australomelanesian lineage. The aboriginal populations in Southeast Asia may have originated in the tropical rain forest of Sundaland, and their direct descendants may be the modern Dayaks of Borneo and Negritos of Luzon. These populations, the so-called "Proto Malays," are possible representatives of the lineage leading to not only modern Southeast Asians, but also the Neolithic Jomon populations in Japan. The present study suggests, moreover, that the Polynesians and western Micronesians have closer affinities with modern Southeast Asians than with Melanesians or Jomonese. PMID- 1605316 TI - Negritos, Australian aborigines, and the "proto-sundadont" dental pattern: the basic populations in east Asia, V. AB - Five evolutionarily significant dental traits were identified from a B-square distance analysis of nine crown characters recorded for several populations of East Asia and Oceania. Intergroup variation in these traits distinguishes three major divisions of the Mongoloid dental complex: sundadonty, sinodonty, and the dental pattern of Australian Aborigines. The Australian crown features may be characterized as having high frequencies of evolutionarily conservative characters. Negritos, one of the probable representatives of indigenous inhabitants of Southeast Asia who may have shared a common ancestor with Australians, possess the more derived sundadont dental pattern. As far as the five crown traits treated here are concerned, Australian dental features may be described as conforming to a "proto-sundadont" dental pattern, applying Turner's terminology. This pattern may represent a microevolutionary step prior to the emergence of the sundadont and sinodont patterns. PMID- 1605317 TI - Population differences in the morphology of the first cervical vertebra. AB - Cephalometric radiographs from 180 healthy Caucasian females, 90 of whom lived in the north of Finland and 90 in the south, were analysed with respect to the morphology of the atlas vertebra. The main findings were a smaller dorsal arch height and a larger ventral arch height in those from the north, including a longer atlas vertebra. These results are interpreted as evidence of morphogenetic reactions to changes in function, in this case a raised head posture attributable to climatic conditions. PMID- 1605318 TI - Multivariate analysis of second trimester midfacial morphology in normal and cleft lip and palate human fetal specimens. AB - To better understand the contribution of congenital dysmorphogenesis to postnatal midfacial dysplasia in individuals with complete cleft lip and palate (CLP), a series of studies were undertaken to investigate age related changes in a number of midfacial components for a sample of 20 normal and 9 complete CLP second trimester fetal specimens. Using data from this sample, the present study assessed the complex multivariate relationships among these variables which represent the fetal normal and CLP midface. Ten variables were standardized relative to crown-rump length and used in Canonical Discriminant Function Analysis (CDFA). CDF analysis revealed that five variables best described the midface and accounted for 72% of the overall variance. These included nasal capsule length, nasal airway volume, premaxillary length, premaxillary volume, and tongue volume. Classification using the CDFA coefficients resulted in correct group membership assignment for 26 of 29 total specimens (89.66%), 8 of 9 cleft (88.9%), and 18 of 20 normal specimens (90.0%). These results suggest that by as early as the second trimester CLP fetuses have a significantly distinct set of midfacial morphological relationships. Some or all of these factors may be responsible for postnatal growth dysplasias noted in CLP individuals. PMID- 1605319 TI - Homology and evolution of the orbitotemporal venous sinuses of humans. AB - The orbitotemporal venous sinuses accompany the intracranial branches of the stapedial artery. These sinuses are large in primitive primates and drain the extensive territories supplied by the stapedial artery as well as the brain. The orbit is drained by a wide cranio-orbital sinus which empties into the postglenoid emissary vein. Also emptying into the postglenoid vein is the petrosquamous sinus. The latter diverts cerebral blood from the transverse sinus and also drains the temporalis muscle. Emptying into both the cranio-orbital and petrosquamous sinuses are meningeal tributaries, which drain the cranial side wall and the dura mater. The relatively small sinus communicans runs in the angle between the petrosal bone and the cranial side wall. It commences at the postglenoid vein and connects the distal end of the petrosquamous sinus to the pterygoid venous plexus. In humans, the orbitotemporal sinus system is greatly modified. Its remnants persist for the most part as "middle meningeal veins." The system no longer drains the orbit, the temporal fossa, or the brain. The petrosquamous sinus becomes attenuated or obliterated along part or all of its length. The postglenoid vein vanishes. The cranio-orbital sinus is reduced in diameter and its connection to the orbit is feeble or absent. During development, the posterior end of the cranio-orbital sinus migrates inferiorly along the sinus communicans. In most individuals, this migration ceases at the foramen spinosum, site of the emissary vein of the sinus communicans. Meningeal tributaries are relatively large in humans, and drain principally into the cranio-orbital sinus or sphenoparietal sinus. The sphenoparietal sinus is an evolutionary novelty restricted to hominoids and is frequently developed in only Homo and Pongo. PMID- 1605320 TI - Molecular and classical cytogenetic analyses demonstrate an apomorphic reciprocal chromosomal translocation in Gorilla gorilla. AB - The existence of an apomorphic reciprocal chromosomal translocation in the gorilla lineage has been asserted or denied by various cytogeneticists. We employed a new molecular cytogenetic strategy (chromosomal in situ suppression hybridization) combined with high-resolution banding, replication sequence analysis, and fluorochrome staining to demonstrate that a reciprocal translocation between ancestral chromosomes homologous to human chromosome 5 and 17 has indeed occurred. PMID- 1605321 TI - Technical note: two programs for performing multigroup longitudinal data analyses. PMID- 1605323 TI - Reading and visual memory: remembering scenes that were never seen. AB - In Experiment 1 (N = 16), under conditions of high memory load (60 pictures and 50 paragraphs) and a 1-week retention interval, undergraduate subjects reported their memory for photographs of scenes (cued recall and free-recall tasks). Subjects frequently reported memory for photographs that they had actually never seen, but had read about in a brief paragraph. In Experiment 2 (N = 40), the same pattern of results was obtained with immediate testing. Experiment 2 also demonstrated that the likelihood of subjects falsely attributing scene memory (based on reading) to actually having viewed a photograph was reduced when metacognitive awareness of imaging during reading was made salient. Awareness of image creation was induced by requiring subjects to rate the paragraphs with respect to imagery vividness. Although other measures of memory remained the same, subjects in the induced-imagery condition made 50% fewer confusion errors than subjects who read the paragraphs without imagery instructions. The results are discussed in the context of Johnson and Raye's (1981) reality monitoring model. PMID- 1605322 TI - Lexical access and the brain: anatomical constraints on cognitive models of word recognition. AB - Recent studies in the cognitive psychology of reading and many other skilled performances have been dominated by models inspired by neural connectivity (e.g., McClelland & Rumelhart, 1986). Such models have not yet begun to consider the accumulating evidence of considerable anatomical localization of component cognitive operations in the human brain (e.g., Posner, Petersen, Fox, & Raichle, 1988). In this article we apply anatomical findings to the job of building computational models of visual word recognition. Brain imaging studies already provide important constraints on how lexical access should be defined in terms of isolable encoding operations that compute the visual form, phonology, and semantics of words. Brain imaging studies also speak to issues of modularity versus interaction between these encoding operations, distribution versus localization of processing within the operations, and orchestration of operations to accomplish different word processing tasks. We conclude that a combined cognitive and anatomical analysis may be of considerable benefit in developing more adequate models of human information processing. PMID- 1605324 TI - Categorical replies to categorical questions by cross-fostered chimpanzees. AB - The chimpanzees Washoe, Moja, Tatu, and Dar were reared under human cross fostering conditions that included the use of American Sign Language (ASL) as the medium of two-way communication. In the course of everyday conversation they were asked, in signs, the Wh-questions that are typically asked of young children. In earlier studies, extensive samples showed a pattern of replies, most significantly a developmental sequence, that closely matched the pattern found in the replies of young children. Part 1 of this report is based on a special sample taken when Tatu was 63 months old and Dar was 56 months old, in which experimenters used a large pool of nameable objects, and asked a naming question and at least one descriptive question about the same object in the same context. Tatu and Dar replied to naming questions (WHAT THAT? or WHAT NAME THAT?) with signs that were nouns and to descriptive questions with signs that were modifiers: possessive pronouns for WHOSE THAT?, colors for WHAT COLOR THAT?, and materials for WHAT THAT MAKE FROM? Part 2 is a reanalysis of the Part 1 sample and several other samples of replies, demonstrating that even when their reply was incorrect, these chimpanzees usually replied with a sign from the category specified by the question. The continuities that biologists seek are continuities of laws, patterns of resemblance rather than overlapping data points. Results reported here add depth to the patterns demonstrated in earlier studies. PMID- 1605325 TI - Memory transfer process: an extension of the Sternberg paradigm. AB - Research conducted by Sternberg (1969) has suggested that there is a transfer process, a cognitive process for activating stored knowledge. His research and that of those who have replicated and extended it have concentrated on distinct declarative lists of information. In two experiments, we have sought to extend this area by studying the cognitive processes for activating an action plan, a sequence of mental operations executed to achieve a goal. Results showed that (a) longer action plans took more time to activate, and (b) when the activation process was interrupted before completion, the process had to be restarted from its beginning after the interruption had been dealt with. These results were interpreted as evidence for a time-consuming transfer process in which the elements of action plans are transferred from long-term store to short-term store. These results are compared with other current data on the transfer process, and implications for the use of controlled knowledge in cognitive tasks are discussed. PMID- 1605326 TI - Is the narrative a reliable method for conducting psychotherapy? PMID- 1605327 TI - The three modes of the science of psychoanalysis. AB - Three modes of the science of psychoanalysis are identified: (1) the domain mode is established when claim is laid for investigation of a distinctive area of nature for investigation. For psychoanalysis, this territory involves human adaptation, mentation, and communication in the emotional arena. This mode essentially is one in which a scientific spirit is central and gross, qualitative observation the source of data and theory; (2) the statistical mode is characterized by quantification (measurement), prediction, controlled study, and global correlational or probability methods. In general, this mode of science serves to confirm, refute, or revise postulates derived from domain-mode observations. An advanced aspect of this mode is termed stochastics, a form of science that deals with events that are both random and deterministic, and which introduces post hoc mathematical equations that are probabilistic in nature. (3) the formal mode is grounded in moment-to-moment observations (time-series data); its results are defined entirely through mathematical treatments of quantified data. The unique quest in this mode is for laws of nature. Each mode of the science of psychoanalysis is discussed for its actual and potential contributions to the field and for its limitations and pitfalls. Finally, the paper discusses aspects of recent research that has, we believe, established a heretofore absent formal mode of science for the field of psychoanalysis. PMID- 1605328 TI - Three quantitative studies of gender and identity in psychotherapy consultations. AB - This paper details the application of three distinctive approaches to the analysis of line-by-line scores for themes of gender and identity in recorded psychotherapy consultations conducted by three male analysts with a female patient. The first method involved commonly used statistical comparisons of the frequency with which gender subthemes and allusions to identity appeared in each consultation session. The results of this study indicate three significantly different patterns of gender material in the communications from the patient with each of the analysts who interviewed her--and from each analyst and patient/analyst system as well. Therapist dominance in this area appeared to be quite strong. The second study involved measures of overall informational complexity for various aspects of the gender/identity sequence of communications. Here too, individual differences emerged. They not only add to the evidence for therapist dominance in these protocols, but also provide indications that sessions differ in respect to the extent to which the information they contain is ordered and repetitive or redundant, as compared to disordered, complex, and varied. The third study availed itself of stochastic methods in which the Box Jenkins models were used to define mathematically and post hoc, the deeper structure of aspects of the vicissitudes of gender/identity expressions in the course of these consultations. The main finding was that change in speaker role in respect to these themes accelerated in response to random interventional shocks to the system that occurred at the time of measurement and inversely with shocks to the system sustained the previous second. This look into the deeper structure of these sequences revealed considerable sensitivity to recent shocks to the patient/therapist system, much underlying instability, and strong tendencies toward establishing stability or equilibrium when the system destabilized. Of note is the finding that all three consultations, by and large, followed the same configuration--itself a rarely seen model. The implications and promise of these methods are discussed. PMID- 1605329 TI - Stochastic analysis of the duration of the speaker role in the psychotherapy of an AIDS patient. AB - This paper has presented a quantitative/stochastic research approach to aspects of a psychotherapy with an HIV-positive patient. The Box-Jenkins (ARIMA) method for time-series analysis was applied to the duration of speaker roles for a single male patient in his first three sessions with a male therapist. The results indicate a definitive underlying stochastic structure of order (1, 1, 1). This indicates that the sequence of speaker durations was nonstationary (chaotic), while the rate at which the sequence changed (velocity) showed a clear structure reflecting the influence on the system of the prior state, and of the prior and present shocks. The histograms of the frequency of utterances of varying time lengths revealed a second deep structure through the emergence of an exponential characteristic of a Poisson model. The Poisson rate constants--a measure of interruption and holding tendencies--were stable across interviews. Intervention analysis identified epochs in each interview that significantly altered the progression of the time series. A qualitative investigation of these periods of destabilization suggested that sudden allusions to highly charged topics, including the likelihood of a fatal outcome of the patient's illness, and especially unconscious criticisms of the therapist by the patient, created a large share of these interludes. Finally, there is a discussion of the limitations and implications of these findings, including a comparison with similar analyses for 6 psychotherapy consultation sessions. PMID- 1605330 TI - The formal mode of the science of psychoanalysis: studies of two patient/therapist systems. AB - This paper has introduced three mathematically based models that are part of a burgeoning new formal mode of the science of psychoanalysis: (1) The Power Spectral Density Function, which investigates the vicissitudes of cyclical power; (2) Work and Force, which lead to measurement of the instantaneous power of a session; and (3) Entropy or Complexity, a measurement of the accumulated complexity or redundancy of the communications from patients and therapists in the course of a therapy session. An additional statistical measurement was included, that of the Measure of Linear Influence or Cross-Correlation Function, which was used with a ten-minute window. Each of these measurements were applied to quantitative data that involved ratings of five variables of emotional communication: Newness of Themes, Extent of Narrative/Imagery, Positively Toned Themes and Images, Negatively Toned Themes and Images, and Continuity of Dialogue within a therapy. The paper compares two psychotherapies using these four measurements. They differentiated the two treatment situations, revealing distinctive properties of each. The implications of these preliminary results are discussed. PMID- 1605331 TI - Psychiatry residency programs: trends in psychotherapy supervision. AB - The evolving dominance of psychobiologic over psychodynamic theoretical influences on education and practice presents new challenges for psychiatry. This article features selected data from the 1989 American Association of Directors of Psychiatric Residency Training annual survey (n = 215) that describe current teaching activities related to psychodynamic psychiatry, mainly psychotherapy. Results are based on a 50 percent return rate (107/215 questionnaires). Responses confirm the emergence of psychobiological (48%) over psychodynamic (40%) departmental orientations and report that the psychodynamic orientation has maintained strength as a secondary emphasis. Residents generally gain experience in a range of psychotherapy theories and modalities, including psychodynamic, cognitive, behavioral, individual, couples, family, and group therapies. Training in brief and short-term individual psychodynamic psychotherapy predominates, however. Use of video- and audiotaping in supervision is limited. Full-time faculty provide the bulk of psychotherapy instruction. This is carried out in both individual and group sessions, which are organized primarily around case reviews. Supervision-related problems include faculty availability, skill diversity, competence, theoretical flexibility, and attitudes, as well as program structure and standards. PMID- 1605332 TI - Assessment factors associated with premature psychotherapy termination. AB - Characteristics of patients accepted for both intensive psychotherapy and psychoanalysis were rated during their initial assessments. Twenty cases that terminated prematurely (most within the first month) were compared with twenty cases that continued in therapy. While neither specific diagnosis, type of insight therapy, nor gender of the patient or therapist was a reliable predictor of premature termination, it was found that psychodynamic and environmental assessment factors significantly differed between these two groups. In those patients who eventually dropped out, specific ego deficits, primarily introspection, frustration tolerance, impulse control, and motivation, were rated as significantly more impaired. The therapists' negative feelings toward their prospective patients and the patients' hostility toward past caretakers and present life circumstances were also associated with premature termination. PMID- 1605333 TI - Consultation in psychotherapy. AB - The value of consultation in good medical practice is equally relevant in the practice of psychiatry including psychotherapy. It is one important example of the need for collaboration in medicine, in clinical, educational, and administrative spheres. Excessive protection of the patient's privacy and the psychotherapist's autonomy can lead to lost opportunity for both participants. Appropriate introduction of the opinion of a respected colleague can have facilitating and creative effects upon the psychotherapy. Difficulty in ongoing psychotherapy often occurs when imbalance develops, and consultation can lead to restoration of an appropriate balance. Long-standing respectful professional association between consulting colleagues can make consultation more comfortable and profitable. It is our opinion that increased readiness to seek appropriate consultations in psychotherapy can be of considerable benefit to psychotherapists, to their patients, and to the consultants with whom they share their concerns. PMID- 1605334 TI - Multiple personality: an issue for forensic psychiatry. AB - The formulation of Multiple Personality (MP) as a distinctive entity by DSM-III while helpful clinically requires, at best, very rigid evaluatory criteria based on independent verification when used as a defense in a Court of Law. The use of the set of eight criteria developed by specialists are helpful guidelines. A case of MP disorder discovered under hypnosis by a psychiatrist and later on vehemently denied by the patient became the object of legal action as part of a malpractice suit. While some well-known experts consulted during treatment believed that she was a MP, the expert witnesses at the trial felt that the patient was not. As a mixed (borderline-histrionic) personality, the patient possibly might have dissociated under stressful life circumstances. The case raises serious issues about the role of auto-suggestion in mimicking MP. It questions the validity of the use of the diagnosis in Court. Legally only carefully evaluated independent data about incongruent past patterns of behavior suggesting alternate personality, can be considered reliable reference for the diagnosis. PMID- 1605335 TI - Merging and emerging realities: simultaneous treatment of parent and child. AB - The purpose of this paper is to invite dialogue concerning the variety of modalities possible in the spectrum of child treatment. Many issues remain to be discussed, such as the child's need to possess the therapist entirely, and the role of other family members. Countertransference issues for the therapist are complex and involve the risk of dual loyalties. Simultaneous treatment shares these concerns with other modalities in the spectrum of child treatment. In simultaneous treatment, as parent and child come to share an experience of being cared for, the possibility arises for the dissolution of polarities. Representations of the past give way to adaptations to current reality. Both the parent's and the child's feelings of rage are contained within the therapeutic matrix of relationships; boundaries are maintained to permit repair and growth. Both parent and child reach new levels of integration as the therapist reinforces boundaries and does not permit intrusion by either the parent or the child into the others arena of playful construction. PMID- 1605336 TI - Administration of rural health services in the Magadan region, USSR, Department of Health. AB - This report explains the administrative and budget procedures of the rural health services in the Yagodnoye District of the Magadan Region. It briefly describes the administrative and budgeting planning relationships between the rural health district, the Magadan health region, and the USSR Department of Health, headquartered in Moscow. In the summary, recommendations for future exchange visits are made such as a program-focused approach. PMID- 1605337 TI - Epidemiology and public health in the Yagodnoye district. AB - Yagodnoye District (population 48,622 as of January 1, 1991) is one of seven administrative districts in the Magadan Region of the Russian Republic, USSR. The population age-distribution is different from that of the United States or Alaska with a larger proportion of persons 20-49 years of age and relatively few people greater than or equal to 60 years of age. Public health and epidemiologic services are provided by a Sanitation and Epidemiology Station with a staff of approximately 108 persons, including 19 doctors. Major activities include Environmental and Occupational Health, Vector Control, Bacteriology Laboratory, and Epidemiology. Epidemiologic services are highly focused on infectious diseases despite the apparent presence of other major public health problems. PMID- 1605338 TI - Alaska/Magadan EMS project: phase two. AB - In July, 1991, five members of the Alaska/Magadan Medical Exchange group visited the Magadan/Chukotka Region of the Soviet Far East, to continue studies of the emergency medical services (EMS) system, and to implement recommendations for system improvement developed during the previous year. During this exchange visit, major efforts focused on development of a rapid defibrillation system for the city of Magadan, technical assistance and training to upgrade burn treatment capabilities, and training and equipping prehospital emergency medical service providers to perform spinal immobilization techniques on traumatic injury patients. Further studies were conducted to compare EMS in the Magadan/Chukotka Region with EMS in Alaska, and recommendations are being presented for further collaborative projects. PMID- 1605339 TI - Report of the mental health team 1991 Alaska/Magadan medical expedition and exchange. AB - This report provides a brief overview of the July, 1991 mental health team visit to the Magadan and Chukotka regions. A previous trip to the region was made by a mental health team in the summer of 1990. The sites covered were Anadyr, Magadan, Yagodnoye and Sinegorye. There are several follow-up activities and projects currently underway, such as a Fetal Alcohol Syndrome project, alcohol treatment comparisons, and Native Elder exchanges. The Soviet economy has had a marked effect in the type of treatments available in hospitals and clinics for all the types of physical and mental health problems. Because of the openness and cooperation of the Soviet medical personnel, much data and information has been gathered and will be used to determine the areas to be addressed for joint study and application. PMID- 1605340 TI - Ophthalmology services in the Magadan region of the Soviet Far East with special reference to diseases of the retina. AB - Ophthalmology Services were observed during the two week period July 4th through 16th, 1991 in Magadan in the Soviet Far East. The range of diabetic eye disease appears to be similar to that observed in the West. Major requirements for education (both patient and physician, stressing the importance of controlling blood glucose and its relationship to diabetic eye disease) and inexpensive reliable diagnostic and therapeutic equipment were identified. Substantial benefits can be achieved by supplementing the current medical infra-structure. Continued medical education through exchange of information remains a primary objective. PMID- 1605342 TI - Magadan pharmacy services update. AB - Pharmacy services in the Magadan Region were visited in order to obtain an update of the current pharmaceutical availability and operation. The first pharmacy visit occurred in July 1990, and is published in the Jan/Mar 1991 issue of Alaska Medicine. PMID- 1605341 TI - Family planning, obstetrical and gynecological health care provision in the Soviet Far East. AB - The Soviet model for both obstetrical and gynecological care and family planning provision seems entrenched in the Soviet Far East as found during a July 1991 visit to the Magadan and Chukotka Regions. Modern birth control is minimally practiced, but does include use of the older Soviet Loop intrauterine contraceptive device (IUD), recent introduction of the new Soviet Copper-T IUD and sporadic availability of condoms and foreign made birth control pills. Without male or female surgical sterilizations being performed, the consequence is that the major form of family planning is first trimester abortion. During this visit, I introduced the use of the NORPLANT Subdermal Contraceptive System and the Copper-T380A IUD to physicians at Anadry and Pevek regional hospitals. Gynecological surgery was also performed and fairly typical ob-gyn care units were toured. Ob-Gyn physicians in the Soviet Far East were found to be highly motivated. They look to the West for help in upgrading family planning and ob-gyn health care in the face of severe shortages after a half decade of perestroika. PMID- 1605343 TI - 1991 Magadan, USSR/Alaska, USA Dental Exchange Program Report. AB - In August 1991, three rural Alaska Public Health dentists made a professionally significant return visit to the Soviet Far East. The city of Magadan was the site for the first actual demonstration of portable American dental equipment and treatment techniques in this remote region of Russia. This exchange was held at several clinical locations and took place during the time of the attempted USSR government coup. PMID- 1605344 TI - Public health in the Magadan region of the Soviet Far East. AB - The impressions formulated from a brief encounter and review of selected health care data from the Magadan Region of the Soviet Far East provides a partial picture of the public health practice along with suggestions for continued collaborative efforts. The health care system appears to be based primarily on a clinical medical model. Tracking of reportable infectious diseases and immunization efforts provides a wide array of information for further analysis. A major activity for future collaboration would be in closing the gap between public health knowledge and practice. The health care staff and health care system appears open to critique and discussion. PMID- 1605345 TI - Instrumental comparison for the determination of cadmium and lead in calcium supplements and other calcium-rich matrices. AB - Three brands of Ca supplement, a laboratory-reagent grade CaCO3 and a certified reference material (International Atomic Energy Agency H-5 Animal Bone) wee analysed for Cd and Pb by four different analytical techniques, viz., anodic stripping voltammetry inductively coupled plasma mass spectrometry, flame atomic absorption spectrometry and electrothermal atomic absorption spectrometry. The Pb levels measured by the four techniques in the bone powder were within the certified Pb level in this certified reference material. Similarly, no significant differences [p less than 0.05; analysis of variance (ANOVA)] were observed in samples with Pb concentrations greater than 1 microgram g-1. However, the Pb levels in the laboratory-reagent grade CaCO3 obtained by flame atomic absorption spectrometry (0.79 micrograms g-1) averaged about three times higher than those measured by the other three techniques (i.e., 0.25 micrograms g-1). Although no significant differences (p less than 0.05; ANOVA) in Cd levels were observed within any of the samples (intra-sample variability), the Cd concentration measured in the different Ca supplements (inter-sample variability) varied by three orders of magnitude (ranging from 0.07 to 3.59 micrograms g-1). PMID- 1605346 TI - Determination of lead in plant tissues: a pitfall due to wet digestion procedures in the presence of sulfuric acid. AB - Two wet digestion procedures for the determination of lead in plant materials by electrothermal atomic absorption spectrometry have been evaluated. The combination of HNO3, H2O2 and HF, though leading to incomplete digestion, yielded values corresponding well with the reference or indicative values of the vegetal tissues used. The mixture of H2SO4, HNO3 and HCIO4 gave results that were too low in some instances, owing to the formation of a mixed precipitate (Pb,Ba)SO4. PMID- 1605347 TI - Determination of lead in wines by hydride generation atomic absorption spectrometry. AB - The optimization of lead hydride generation in aqueous ethanolic media and the influence on its generation of the wine components, both white and red, have been studied. These interferences were overcome by careful control of the parameters affecting hydride generation and the procedure was applied to the determination of Pb in wines. The method is fast, accurate and sensitive and can be used to quantify 24 ppb of Pb in wines. PMID- 1605348 TI - Development and evaluation of analytical methodology for the determination of aflatoxins in palm kernels. AB - A rapid, simple and reproducible method for the simultaneous estimation of aflatoxins AFB1, AFB2, AFG1 and AFG2 in palm kernel samples has been developed by optimizing the sample preparation, solvent extraction, sample clean-up and quantification procedures. The aflatoxins are extracted from a slurried palm kernel sample with an acetone-water (80 + 20, v/v) mixture and the crude extract is cleaned up by solid-phase extraction using a phenyl bonded phase cartridge. The extract is passed through the cartridge with a water-methanol (93 + 7) mixture. Subsequent elution of the aflatoxins retained on the cartridge is achieved with a 3 ml aliquot of chloroform. The aflatoxin content of the eluate is quantified using a bi-directional high-performance thin-layer chromatography procedure. A critical evaluation of the proposed method was carried out by statistical comparison with the British Standard Method. The proposed procedure was shown to be more efficient and precise. Consistent recoveries of over 90% were achieved from spiked palm kernel extracts and detection limits were found to be 3.7, 2.5, 3.0 and 1.3 micrograms kg-1 for AFB1, AFB2, AFG1 and AFG2 aflatoxins, respectively. PMID- 1605349 TI - Thin-layer chromatographic detection of pyrethroid insecticides containing a nitrile group. AB - A spray reagent for the detection of pyrethroid insecticides containing a nitrile group by thin-layer chromatography is described. These insecticides on alkaline hydrolysis yield cyanide ion, which in turn reacts with copper(II) acetate and o tolidine in an acetic acid medium to give a blue colour. Organochlorine, organophosphorus and carbamate insecticides do not interfere. The limit of detection is about 1 microgram. PMID- 1605350 TI - Colorimetric method for the quantitative determination of the antibilharzial drug praziquantel and its application to pharmaceutical preparations. AB - A method for the colorimetric assay of praziquantel has been developed. For the colorimetric assay, it was necessary to hydrolyse praziquantel with 3 mol dm-3 NaOH, 6 mol dm-3 HCl and 85% phosphoric acid separately. 4-Chloro-7-nitro-2,1,3 benzoxadiazole (NBD-Cl) reacts with the basic hydrolysis product in methanolic aqueous phosphate buffer (pH 7.4), resulting in the formation of an orange product with a characteristic absorption maximum at 478 nm. The red-orange product of the interaction between the hydrochloric acid hydrolysis product and NBD-Cl showed an absorption maximum at 486 nm. The colours obtained were stable for 24 h. The colour system obeyed Beer's law in the concentration range 2-15 and 2-18 micrograms ml-1 for the basic hydrolysis product and the acid hydrolysis product, respectively. The results obtained showed good recoveries with relative standard deviations of 0.378 and 0.47% for the basic and the acid hydrolysis product, respectively. The determination limit was found to be 0.124 and 0.150 micrograms ml-1 for the praziquantel basic hydrolysis product and the acid hydrolysis product, respectively. The coloured reaction products obtained with the proposed method were synthesized. The structures of these products were studied and the compounds identified. PMID- 1605351 TI - Application of tryptamine as a derivatizing agent for the determination of airborne isocyanates. Part 5. Investigation of tryptamine-coated XAD-2 personal sampler for airborne isocyanates in workplaces. AB - The development of an efficient solid sorbent personal sampler with increased convenience for sample collection in workplaces is described. Several solid sorbents were coated with tryptamine, and sampling tubes were prepared with the coated sorbents. These tubes were evaluated for the collection of phenyl isocyanate vapour generated in a commercial test atmosphere generation system that permits the simultaneous collection of up to 12 uniformly loaded samples. Tryptamine-coated XAD-2 resin was shown to be the most efficient solid sorbent for the collection of airborne phenyl isocyanate. The optimum amount of tryptamine needed for coating XAD-2 resin was investigated. PMID- 1605352 TI - Rapid ultraviolet spectrophotometric assay of benzoyl metronidazole in an oral suspension. AB - A procedure is described for the rapid determination of benzoyl metronidazole in an oral suspension which is based on measurement of the change in absorbance at 276 nm during alkaline hydrolysis of the compound in 2 mol dm-3 NaOH. The change in absorbance follows a linear relationship with concentration in the range 3-18 micrograms ml-1. Results of the determination of benzoyl metronidazole in an oral suspension and of the recovery experiments performed on this formulation, and also on various individual excipients and other additives, confirmed the applicability of the proposed method to complex formulations. PMID- 1605353 TI - Simultaneous determination of acetylsalicylic acid and its major metabolites in human serum by second-derivative synchronous fluorescence spectrometry. AB - A method is described for the simultaneous determination of acetylsalicylic, salicylic, gentisic and salicyluric acids (ASA, SA, GA and SU, respectively) in serum, based on their native fluorescence. The ASA-SA-GA-SU-containing serum samples are extracted with chloroform-1% acetic acid solution; ASA and SA are determined in the organic phase, and GA and SU in the aqueous phase, after removal of protein with trichloroacetic acid, at pH 5.0 and 11.6, respectively. The ASA-SA and GA-SU-SA mixtures are resolved using second-derivative fluorescence spectrometry and the appropriate empirical equations involving the effect of each acid on the signal of the other. Recoveries from sera spiked with ASA (1.0-10 micrograms ml-1), SA (25-50 micrograms ml-1), GA (0.05-0.2 micrograms ml-1) and SU (1.0-5.0 micrograms ml-1) ranged from 100 to 104% (mean 101%), from 93 to 99% (mean 97%), from 94 to 104% (mean 99%) and from 94 to 107% (mean 98%), respectively. PMID- 1605354 TI - [Anatomy in Hungary and the Society of Anatomy]. PMID- 1605355 TI - From somites to vertebral column. AB - We report on the development and differentiation of the somites with respect to vertebral column formation in avian and human embryos. The somites, which are made up of different compartments, establish a segmental pattern which becomes transferred to adjacent structures such as the peripheral nervous system and the vascular system. Each vertebra arises from three sclerotomic areas. The paired lateral ones give rise to the neural arches, the ribs and the pedicles of vertebrae, whereas the vertebral body and the intervening disc develop from the axially-located mesenchyme. The neural arches originate from the caudal half of one somite, whereas the vertebral body is made up of the adjacent parts of two somites. Interactions between notochord and axial mesenchyme are a prerequisite for the normal development of vertebral bodies and intervening discs. The neural arches form a frame for the neural tube and spinal ganglia. The boundary between head and vertebral column is located between the 5th and 6th somites. In the human embryo, proatlas, body of the atlas segment, and body of the axis fuse to form the axis. PMID- 1605356 TI - [In memoriam Edward C. Roosen-Runge]. PMID- 1605357 TI - [Biomechanical problems of upright posture]. PMID- 1605358 TI - The detailed functional anatomy of the ligaments of the vertebral column. PMID- 1605359 TI - [The role of the vertebral joint for the kinetics of the moving segment]. PMID- 1605360 TI - [Structure and function of the intervertebral disks]. PMID- 1605361 TI - August Rauber. PMID- 1605362 TI - Elements of a general theory of joints. 7. Mechanical structures of the relative motion of adjacent vertebrae. AB - The mechanical structure of the relative motion of adjacent vertebrae is given by the interplay of the artt. zygapophysiales, the intervertebral disk and the ligaments, respectively. This structure will be described in the 3 main functional planes. Horizontal plane (parallel to the disk): The two artt. zygapophysiales structurally represent a force locked, kinematically contrained four-bar-chain (link quadrangle). It possesses but one degree of freedom. The intervertebral disk does not influence, therefore, the kinematic structure but the extent of the motion. Frontal-coronal plane: The four-bar-chain of the frontal plane seems to be inflexible. Lateral bending is only possible combined with a right or left handed axial rotation. Vertical-sagittal plane: The artt. zygapophysiales work as a single dimeric link chain. The momentary rotational center lies on the common normal of the two articular surfaces. Its position upon that is determined by the geometry of the applied force system according to the "reciprocal theorem of synarthroses". Solely one direction of translation is possible. A translation perpendicular to the intervertebral disk is impossible in the cervical and thoracic region. PMID- 1605363 TI - Structural and molecular plasticity in the dorsal horn: a genuine model for neuronal and synaptic group selection. PMID- 1605364 TI - Collagen production by human smooth muscle cells isolated during intestinal organogenesis. AB - The extracellular matrix influences organogenesis by modulating cell behavior. In humans, collagen is the major matrix constituent of the adult intestinal wall and is synthesized by smooth muscle cells. The objective of the current study was to examine collagen production by fetal human intestinal smooth muscle cells isolated during intestinal morphogenesis. Techniques were developed for the isolation and culture of human fetal intestinal smooth muscle cells. The cultured cells were confirmed as muscle by immunohistochemical stains for cytoskeletal filaments and documentation of contractile behavior. In culture, these cells stained for mesenchymal and muscle cytoskeletal proteins: vimentin, actin, and desmin, and did not stain for neural or epithelial markers. The muscle cells contracted in response to acetylcholine, in contrast to human fetal dermal fibroblasts which did not contract appreciably. Collagen production was assayed by the uptake of [3H]-proline into collagenase-digestible protein. Collagen production was greatest at 11 weeks gestation, the youngest age studied. By 20 weeks gestation, collagen production had decreased to adult levels. However, when compared to another matrix-producing fetal mesenchymal cell, the dermal fibroblast, intestinal smooth muscle cells produced twice as much collagen. Collagen types were determined by polyacrylamide slab gel electrophoresis. Smooth muscle cells predominantly produced types I and III collagen alpha chains. Therefore, collagen production is a significant function of human fetal intestinal smooth muscle cells, and probably plays a major role in the development of intestinal structure. The in vitro model presented here provides a means of studying the regulation of this collagen production throughout intestinal organogenesis. PMID- 1605365 TI - Neuroactive amino acids in the area postrema. An immunocytochemical investigation in rat with some observations in cat and monkey (Macaca fascicularis). AB - The localization of five neuroactive amino acids in the rat area postrema was studied by postembedding immunocytochemistry in semithin and ultrathin sections. Antisera to GABA, glycine, glutamate and aspartate produced labelling of cells that were identified as neurons in the electron microscope. GABA-like and glycine like immunoreactivities occurred in about 20% and 60% of the neurons, respectively, and a minor proportion of the cells displayed both immunoreactivities, suggesting a cellular colocalization of GABA and glycine. Immunoreactivities for glutamate and aspartate were found in a large majority of the neurons, including most of the cells that were positive for GABA and/or glycine. Taurine immunoreactivity was highly concentrated in a few small cells with ultrastructural features typical of microglial cells, and in processes that were probably derived from these. Taurine also appeared to be abundant in cells confined to the perivascular space. The electron microscopic, immunogold analysis of the neuropil revealed numerous nerve terminals that were enriched in GABA or glutamate immunoreactivity, compatible with a transmitter role of these amino acids. Glycine immunolabelling was found preferentially in postsynaptic elements, suggesting that the glycine-containing cells lack locally ramifying axon collaterals, and that they mainly project outside the area postrema. Aspartate immunolabelling was also generally low in axon terminals. This is similar to the situation in several other brain areas and could indicate that the latter amino acid primarily serves metabolic functions in the area postrema. PMID- 1605366 TI - Ultrastructural study of ascending projections to the lateral mammillary nucleus of the rat. AB - We examined the synaptic organization of ascending projections from the pars ventralis of the dorsal tegmental nucleus of Gudden (TDV) and the laterodorsal tegmental nucleus to the lateral mammillary nucleus (LM). The LM neuropil consists of terminals containing pleomorphic synaptic vesicles and forming symmetric synaptic contact, and terminals containing round synaptic vesicles and forming asymmetric synaptic contact. They make up 63% and 37%, respectively, of all axodendritic terminals. All axosomatic terminals contain pleomorphic vesicles and make symmetric contact. Following injection of WGA-HRP into the TDV, many anterogradely labeled terminals and retrogradely labeled cells are found in the LM. Labeled terminals contact mainly proximal (more than 2 microns diameter) and intermediate (1-2 microns diameter) dendrites. Serial ultrathin sections of the LM show that 55% of axosomatic terminals are labeled anterogradely. Following injection of WGA-HRP into the laterodorsal tegmental nucleus, many anterogradely labeled terminals are found in the LM, but no retrogradely labeled cells are present. Labeled terminals contact mainly distal (less than 1 micron diameter) and intermediate dendrites as well as somata. In the LM neurons, 46% of axosomatic terminals are labeled anterogradely. All labeled terminals from these nuclei contain pleomorphic vesicles and make symmetric synaptic contact. These results indicate that almost all axosomatic terminals come from the TDV and the laterodorsal tegmental nucleus, which send inhibitory inputs to the lateral mammillary nucleus. PMID- 1605367 TI - Postnatal development of the rat organ of Corti. I. General morphology, basilar membrane, tectorial membrane and border cells. AB - The development of the rat organ of Corti was studied during the first postnatal weeks. The temporal and the spatial patterns of cochlear development were investigated between 4 and 24 days after birth by means of semi-thin sections at approx. ten equidistant positions along the entire cochlear duct. At all examined positions width, thickness and cross sectional area of basilar membrane, cross sectional area of tectorial membrane, of cells of Hensen, Claudius and Boettcher and of the organ of Corti were quantitatively analyzed. The most conspicuous maturational changes occur between 8 and 12 days after birth. These are the detachment of the tectorial membrane, the first appearance of filaments within the basilar membrane, the formation of the tunnel of Corti and the opening of the inner spiral sulcus. Quantitative analysis revealed that structures of a given position along the cochlear duct do not develop synchronously. Width of the basilar membrane and cross-sectional area of the tectorial membrane are already mature at the onset of hearing (10-12 days after birth). Length, thickness and cross-sectional area of the basilar membrane as well as cross-sectional area of the organ of Corti and of the cells of Hensen, Claudius and Boettcher still develop after the onset of hearing (up to 20-24 days after birth). We suggest that basic cochlear function is established by structures which are mature before the onset of hearing. Cochlear structures which develop after the onset of hearing might be involved in this improvement during this period. PMID- 1605368 TI - Postnatal development of the rat organ of Corti. II. Hair cell receptors and their supporting elements. AB - The development of cochlear receptor cells and their supporting elements was studied by means of semi-thin and ultra-thin sections during the first postnatal weeks in the rat. The temporal and spatial patterns of the receptor cell development were investigated between the 4th and 24th days after birth. At approx. ten equidistant positions along the entire cochlear duct length of inner and outer hair cells, width of outer hair cell triad and stereocilia-length of the outer hair cells were quantitatively analyzed. Striking maturational changes take place before the 12th day after birth, that is, when the onset of hearing occurs. These changes are the formation of the tunnel of Corti, of the Nuel spaces, the appearance of filaments within the supporting elements and the change in cell shape of the hair cells. Between 4 days and 20 days after birth the maturation of outer hair cells is characterized by a decrease of organelles in the cytoplasm and establishment of the subsurface cistern. The quantitative analysis revealed a unique developmental pattern of the length of the outer hair cells, the width of the outer hair cell triad and the stereocilia length of the outer hair cells. Shortly after birth these structures have an almost constant size along the whole cochlear duct, but with increasing age the structures shorten at the cochlear base and enlarge at the apex. This pattern results in the establishment of a baso-apical gradient of the above mentioned structures. We assume that this baso-apical gradient is of central importance for the frequency representation. PMID- 1605369 TI - A segmented pattern of cell death during development of the chick embryo. AB - During the early development of the chick embryo, specific groups of cells die in characteristic patterns. In this study, Nile Blue sulphate staining was used to reveal a novel pattern of segmentally repeated cell death in the paraxial mesoderm of the chick prior to stage 23. This pattern varies according to the developmental stage of the embryo and shifts rostrocaudally, corresponding to progressing somite differentiation. Initially, during early somite differentiation, cell death is restricted to the rostral half of the somite (the rostral pattern of cell death). After the somite has differentiated into dermomyotome and sclerotome, dead cells appear in superficial tissues in a pyramidal pattern which lies in register (rostrocaudally) with the central part of the sclerotome. Finally, small bands of dying cells are seen between the neural tube and the expanding sclerotome. This third pattern (the ventral path) lies in register with the rostral part of the caudal half of the sclerotome. We show by fluorescent labelling of the migrating neural crest that these patterns of cell death correspond to the routes of neural crest migration. In addition, serial sectioning of stage 23 chick embryos confirms that the position of dying cells correlates with the known routes of neural crest migration and with the sites of development of certain neural crest-derived tissues. PMID- 1605370 TI - Development of the tectum and diencephalon in relation to the time of arrival of the earliest optic fibres in Xenopus. AB - The development of the tectum and diencephalon in Xenopus has been investigated in relation to recent descriptions of the establishment of the retinotectal projection. Tritiated thymidine autoradiography and bromodeoxyuridine immunohistology were used to identify the stages at which cells became postmitotic. Cells in the diencephalon were found to become postmitotic before cells in the tectum. At the time of arrival of the first optic fibres (stage 37/38) no postmitotic cells appeared to be present in the tectal precursor region. The first postmitotic cells which could be definitely assigned to the tectum appeared between stages 41 and 45. The results suggest that the initial retinotopic ordering of optic fibres observed from stage 37/38 relates to the position of fibres in the optic tract and not the tectum. PMID- 1605371 TI - Immunolocalization of laminin, heparan-sulfate proteoglycan, entactin and type IV collagen in the rat anterior pituitary. II. An in vitro study on primary cultures. AB - The distribution of four basement membrane components: laminin (LAM), type IV collagen (Coll. IV), heparan-sulfate proteoglycan (HSPG), and entactin (ENT), was studied by immunocytochemistry in primary cultures of adult rat anterior pituitaries. In such cultures, the pituitary cells are deprived of their normal environment of adjacent cells and basement membranes (BM), and of the connectivo vascular system of the hypophysis. In this dissociated system, pituitary cells grow as small clusters upon a monolayer of fibroblasts. LAM was found highly expressed in endocrine and in folliculo-stellate cells. Very small amounts of Coll. IV, but neither HSPG nor ENT, could be detected in endocrine cells. In contrast, in fibroblasts, very large amounts of Coll. IV, HSPG, and ENT, and a lower quantity of LAM were detected. At the ultrastructural level, the immunoreactive components present within the cells were located in the subcellular compartments involved in the elaboration of exported products. In addition to that intracellular distribution, the four constituents were observed in an extracellular matrix which appeared between the cultured cells, either as an amorphous material, or as a more or less dense reticular network, weakly stained with anti-LAM, but strongly stained with the other antibodies. Thus, the present immunocytochemical data support the implication of pituitary endocrine cells, at least for LAM secretion, in the elaboration of a novel extracellular matrix in primary cultures. In addition, a cooperation with non-endocrine cells seemed to be required for the production of the four BM components. PMID- 1605372 TI - Mammotropes and somatotropes in the adenohypophysis of androgenized female mice: morphological and immunohistochemical studies by light microscopy correlated with routine electron microscopy. AB - Female mice were divided into androgenized (AF) and control (CF) groups. The AF mice were injected subcutaneously with testosterone propionate (Tp) and the CF mice with sesame oil at 5 days of age. Mammotropes (PRL cells) and somatotropes (GH cells) in the adenohypophyses of these mice when they became adults were studied with immunohistochemistry and morphometry by light microscopy correlated with routine electron microscopy. In CF mice, almost all of the PRL immunoreactive cells (about 43% of all parenchymal cells) were type I (classical) PRL cells, and almost all of the GH-immunoreactive cells (about 30% of all parenchymal cells) were type I (classical) GH cells. Type II PRL cells accounted for about 0.4% of parenchymal cells, and type II GH cells were about 2.5% of all parenchymal cells. In AF mice, the percentages of PRL and GH cells were not significantly different from those of CF mice. Mammosomatotropes (Ms cells) in both groups were less than 1% of all parenchymal cells. Numbers of all parenchymal, PRL and GH cells, however, were increased significantly in AF mice when compared to those in CF, because the adenohypophysis was increased in volume in AF mice. Type I PRL cells were larger in AF than in CF. The ultrastructure suggested that type I PRL cells may show increased PRL synthesis and secretion in AF mice. Furthermore, AF mice, in which the hypothalamus is masculinized by the neonatal treatment with Tp, retained feminine characteristics in the population and size of PRL cells and GH cells in the adenohypophysis. PMID- 1605373 TI - Postnatal development of the cervical epithelium in the Mongolian gerbil. AB - This study analyzes the postnatal development of the Mongolian gerbil's cervical epithelium, in relation to its future functions. In the newborn gerbil the outline of the cervical canal is smooth, showing hardly any signs of folding. The epithelium consists of 1 to 3 layers. The cervical cells have rounded apices of regular outline and contain a large amount of glycogen. The first secretory products of specific mucus type appear about day 23 postnatally (p.n.). Initially two types of vesicles can be identified, as compared with only one type in sexually mature animals. The process of mucification begins in the vagina and the external os of the cervix and spreads towards the cervical horns. The cervical canal, besides growing longer, becomes increasingly folded during development. At about day 50 p.n., with the onset of sexual maturity, an upper endocervix and a lower ectocervix can be distinguished within the cervical canal. In the fully mature animal, the endocervix consists of 4 to 5 layers, in which apical cells mucify and exfoliate. In the ectocervix, the epithelium can be divided into 4 to 5 basal layers and 5 to 7 upper layers which mucify, keratinize, and exfoliate, according to the cyclic phases of the vagina. Diapedesis of leucocytes through the epithelium starts around day 45 p.n. PMID- 1605374 TI - The neuroepithelial cells of the fish gill filament: indolamine immunocytochemistry and innervation. AB - The neuroepithelial cells (NECs) of the fish gill filament share several morphofunctional features with the cells of the neuroepithelial bodies in the lungs of air-breathing vertebrates. In the present study, a detailed indolamine immunocytochemical analysis of the branchial neuroepithelial cells and nerves was undertaken in non-teleost and teleost species, with particular emphasis on the latter. In the rainbow trout, Oncorhynchus mykiss, the chemical degeneration of either catecholaminergic (by 5- and 6-hydroxydopamines) or indolaminergic (by 5,6 dihydroxy-tryptamine) innervations associated with the NECs was studied using electron microscopy. In teleosts, the NECs are located primarily on the distal half of the filament. In the trout particularly, these cells are innervated mainly by non-indolaminergic nerves taking up sympathetic neurotoxins. The proximal half of the filament contains isolated NECs innervated additionally by intrinsic indolaminergic neurons. Serotonin-like immunoreactivity of the NECs is evident in the granular vesicles packed within the basal soma and processes which surround non-vascular and vascular smooth muscles in the filament. Apical processes from the neuroepithelial cells occasionally contact the water on the surface of the filament epithelium. The secretory function of the NECs is discussed with reference to the probable involvement of serotonin in the modulation of fish gill function. In addition, their connections with both central and branchial nervous systems suggest a possible chemoreceptor role. PMID- 1605375 TI - Effect of growth on architecture of rat semimembranosus lateralis muscle. AB - Architecture of semimembranosus lateralis muscle (SMl), an almost parallel fibered muscle with bony origin and aponeurotic insertion of its muscle fibers, was studied in male Wistar rats of two age groups. Using photographic techniques and maximal stimulation active muscle architecture was determined at muscle optimum length. Muscle length increases were almost similar with fiber length increases (approximately 36%). Aponeurosis length increased (by 31%) as did angle of the aponeurosis with the line of pull (approximately 4 degrees). Angles of the proximal as well as distal fibers with the line of pull were unchanged. Increases in mean fiber diameter were estimated to be approximately 50%. It is likely that increased mean fiber diameter was accommodated at the bony origin by enlargement of its area. At the aponeurosis increased mean fiber diameter was accommodated by increased length of the aponeurosis as well as a change in fiber angle with the aponeurosis. This change in fiber angle proved to be different in the proximal and distal part of the aponeurosis. Under the assumption of a uniform change in fiber diameters, a gradient of length change along the aponeurosis occurs. It is concluded that growth in an almost parallel-fibered muscle with a bony attachment results in different architectural adaptations in the parts close to the bony attachment as compared to those close to the aponeurosis. This difference is due to the fact that adaptation of aponeurosis angle with the line of pull occurred, which was not the case for angle of the line of origin with the line of pull. PMID- 1605376 TI - Development and cytodifferentiation of peritubular myoid cells in the rat testis. AB - The cytodifferentiation of peritubular myoid cells was studied in developing rats from fetal day 18 through approachment of puberty. The parameters taken into consideration were 1) the presence of desmin, a component of intermediate filaments in contractile cells; 2) the expression of alkaline phosphatase, a cell surface enzyme present in no other cell type of the seminiferous tubule; 3) the expression of the smooth muscle specific isoform of alpha-actin, a marker of terminal differentiation in smooth muscle cells; 4) cell proliferation rate, evaluated in radioautography as labeling index after incorporation of 3H thymidine in short-term organ culture; and 5) cytoarchitectural changes detected with scanning electron microscopy. By means of immunofluorescence and cytochemistry it was observed that the three markers are expressed early during life, long before the onset of the first spermatogenic wave; in particular desmin is already present in fetal samples and alkaline phosphatase activity appears a few days after birth, whereas alpha-smooth muscle isoactin is first detected around birth. As for myoid cell replication, the high prenatal labeling index was found to drop soon after birth and to further slow down during the first month of postnatal life, suggesting that myoid cell proliferation is not a major factor in peritubular expansion. SEM examination of developing peritubulum has shown that, when approaching puberty, the myoid cell undergoes a dramatic change in cytoarchitecture, consisting in extreme flattening and cytoplasmic expansion resulting in an apparent increase in peritubular surface. PMID- 1605377 TI - Immunoelectron microscopic localization of laminin in rat ovarian follicles. AB - We studied the immunohistochemical and ultrastructural distribution of laminin in ovaries of immature and mature rats. When sections from 1-8-week-old rat ovaries were labeled directly with conjugates of affinity purified anti-laminin IgG horseradish peroxidase (HRP), the antibodies bound to all ovarian basement membranes including those surrounding follicles in different stages of maturation. In addition, intracellular labeling was seen in granulosa and theca cells of follicles undergoing rapid development (preantral and antral stages) and in basement membrane-like structures of the Call-Exner bodies. Intracellular laminin was generally not detected, however, in any cells of primordial or atretic follicles. Tissue processed for immunoelectron microscopy 1 hour after the intravenous injection of anti-laminin IgG-HRP showed binding of antibody in linear patterns along endothelial and follicular epithelial basement membranes. Discontinuous strands of laminin-positive, extracellular matrices were also seen between theca cells of all follicles. In addition, injected anti-laminin IgG labeled perisinusoidal basement membranes located within corpora luteae and patches of basement membrane material between granulosa lutein cells. When ovaries were examined 5 d after the intravenous injections of anti-laminin IgG HRP, uneven or segmented labeling was found in subepithelial basement membranes surrounding developing follicles. Our results therefore indicate that granulosa and theca cells participate directly in basement membrane laminin biosynthesis and suggest that this new laminin is spliced into existing basement membranes during follicular growth. PMID- 1605378 TI - Reexamination of the morphology of the extratesticular rete and ductuli efferentes in the goat. AB - The morphology of the extratesticular rete and ductuli efferentes was reexamined in serial cross sections collected from the entire mass of the efferent ductules and in longitudinal sections collected from the partially unraveled efferent ductules. The extratesticular rete forms a 3-4-mm-long sac-like dilatation, which, within the head of the epididymis, has a wide lumen (up to 4 mm) and gives off along its length numerous evaginations, which, in turn, make connections with the ductuli efferentes. The latter is a mass of 16-18 ductules lined by three types of nonciliated cells: type II cells are characterized by dense, periodic acid-Schiff (PAS)-positive granules; type III cells are characterized by empty appearing, PAS-negative vacuoles; and type I cells lack both granules and vacuoles. The distribution of the three types of nonciliated cells varies along the length. Whereas only type I cells are present in the beginning portion of the efferent ductule, type II cells predominate in the middle portion and type III cells in the distal portion (near the epididymis). The transition from one cell type to the other type is gradual; thus there are short segments along the length that share characteristics first for type I and type II cells and then for type II and type III cells. These results demonstrate that different nonciliated cell types are not randomly distributed in the epithelium of the ductuli efferentes but, instead, gradually differentiate from type I to type II to type III cells along the length of each efferent ductule. Factors controlling this differentiation remain to be studied. PMID- 1605379 TI - Localization of actin, alpha-actinin, and tropomyosin in bovine spermatozoa and epididymal epithelium. AB - Actin, alpha-actinin, and tropomyosin were localized in the testicular, epididymal, and ejaculated spermatozoa and in the epithelium of the bovine epididymis by means of specific antibodies using an indirect immunofluorescence technique. Immunocytochemical results were confirmed by the western blot analysis. Independent of the method of fixation, washing, or sonication, actin, alpha-actinin, and tropomyosin were all consistently localized in the neck of the spermatozoa. Actin and tropomyosin present in the postacrosomal area could be removed by sonication, whereas alpha-actinin in the basal plate appeared to be resistant to the treatment. In the unwashed spermatozoa alpha-actinin-specific immunofluorescence was seen over the acrosomal area, whereas in the washed sperm it appeared as a narrow cap at the margin of the head. In the latter location, its distribution was similar to that of tropomyosin. In the majority of preparations, tropomyosin could be localized in the principal piece of the tail. Even though some actin-specific immunofluorescence could be identified in the principal piece of the tail of the testicular and epididymal spermatozoa, a strong immunoreaction appeared only in the ejaculated spermatozoa. In the principal cells of the epididymal epithelium, specific fluorescence for actin, alpha-actinin, and tropomyosin occurred in the apical junctional complex. Basal bodies of the solitary cilia of the epididymal epithelium were labelled with antitropomyosin and anti-alpha-actinin antibodies. Besides offering new information about the cytoskeletal composition of the mammalian sperm, the present results support the hypothesized homology between the connecting piece of the sperm neck and the basal body of the cilia. PMID- 1605380 TI - Renewal of enterochromaffin cells in the rat caecum. AB - The localization, morphology, and neurohormonal peptide content of neuroendocrine cells have been extensively investigated. Relatively little is known about the kinetics of growth and differentiation of these cells. We studied the kinetics of enterochromaffin (EC) cells in the caecum of the rat, by applying the thymidine analogue 5-bromo-2'-deoxyuridine (BrdU), to identify cells in S-phase, administered in pulse-chase and synchronous continuous labeling experiments. By double indirect immunofluorescence staining of tissue sections, using antibodies against serotonin and BrdU, percentages of BrdU positive EC cells could be enumerated, from which cell-kinetic parameters were derived. The following conclusions were drawn: 1) EC cells are renewed by proliferation of EC cells and by recruitment from proliferating precursor cells. 2) Caecal EC cells appear to consist of a relatively rapidly renewing and migrating fraction (60-65%) with a turnover time of approximately 16 days and a relatively slowly renewing and possibly stationary fraction (35-40%) with an estimated turnover time of approximately 150 days. 3) Seventy percent of the EC cells are localized in the lower half of mucosal crypts, 30% in the upper half. After prolonged labeling the percentage of labeled EC cells in the lower crypt half always exceeds that in the upper crypt half. This decrease in labeled EC cells during migration towards the mucosal surface indicates loss of endocrine cells, possibly owing to loss of endocrine characteristics. PMID- 1605381 TI - Distribution of gonadotrophins within the anterior pituitary cells of the musk shrew (Suncus murinus L.). AB - Gonadotrophs in the anterior pituitary gland of the musk shrew were first identified by means of electron microscopic immunocytochemistry. The gonadotrophs of the musk shrew revealed quite unusual ultrastructural features that have never been seen before in other species. These cells contained two types of secretory granules, i.e., small dense, round-shape granules and large lucent, irregular shape granules. FSH beta and LH beta were mostly observed together on both small and large secretory granules. The distribution pattern of the subunits of gonadotrophs was slightly altered following gonadectomy in the musk shrew. PMID- 1605382 TI - Intercellular communication within the rat anterior pituitary gland: IV. Changes in cell-to-cell communications during pregnancy. AB - Cell-to-cell communication by gap junctions was investigated in the female rat anterior pituitary gland from 9 through 21 days of pregnancy and subsequently on days 2 and 20 of the lactational period. Compared with intact estrus females, the major morphological characteristics of the pituitary gland during pregnancy were remarkably developed prolactin cells and gonadotrophs. A close relationship of both cell types was clearly evident. Gap junctions were present at each of the time intervals studied; however, they were noted only between adjacent folliculo stellate cells. No remarkable changes were noted in the number of gap junctions during the middle stage of pregnancy (day 9 through day 15), with the relative number resembling that found in intact, 90-day-old controls during estrus (0.47 +/- .01 junctions/follicle-control vs. 0.50 +/- 0.08--day 15 of pregnancy). In the later stages of pregnancy (day 17 through day 21), a demonstrable increase was observed (0.64 +/- 0.10--day 17, 0.79 +/- 0.11--day 19 and 0.72 +/- 0.12--day 21), whereas during the lactation, this pattern returned to that seen at midpregnancy. Since both prolactin and the gonadal steroid hormones dramatically fluctuate during pregnancy and lactation, it is postulated that they may have an active role in gap junction formation during these two phases of reproductive life. PMID- 1605383 TI - The microcirculation of bone and marrow in the diaphysis of the rat hemopoietic long bones. AB - The nature of the microcirculation of the diaphyseal portion of long bones and the adjacent bone marrow is poorly understood. The purpose of this study was to describe the blood supply in the diaphyseal cortex and the relationship of the bone vascular circulation to that of the bone marrow in the growing rat. India ink-gelatin was infused in the arterial system of 3-month-old rats and the vascularization was determined from histological sections. In some studies the periosteal circulation was blocked but the nutrient and metaphyseal arteriole systems were left intact. In the growing rat, most of the vascular flow appears to be centripetally through the diaphyseal cortex and this appears to be the primary blood supply for the adjacent bone marrow. The India ink traversed the cortex and entered the marrow through osteal canals at the endocortical surface. At the marrow-endocortical bone surface interface, ink exiting from the osteal canals filled the adjacent marrow sinusoids in what appeared as "bush-like" structures. From the bone marrow the ink appeared to drain into the central vein. Some arterioles from the nutrient system were found to penetrate the inner two thirds of the cortical bone and then re-enter the bone marrow. The centripetal flow of blood and the importance of the cortical flow for perfusion of the hemopoietic tissue was further documented when periosteal flow was obstructed. In this situation, the cortical bone and adjacent bone marrow were not perfused while the nutrient system and central vein were filled with ink.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605384 TI - Morphological observations supporting muscle fiber hyperplasia following weight lifting exercise in cats. AB - Although exercise-induced muscle fiber hyperplasia has been demonstrated through direct fiber counts following nitric-acid digestion of muscle, morphological studies to determine the mechanism of hyperplasia have not been performed previously. In this study, light and electron microscopy were used to evaluate evidence of muscle fiber splitting or de novo formation of new muscle fibers. Since both fiber hypertrophy and hyperplasia may result in alterations in the muscle nuclear populations, myonuclear number and satellite cell frequency were assessed quantitatively to determine their role in regulating muscle fiber size. Ten adult cats performed weight-lifting exercise, and the right (exercised) and left (control) forelimbs were fixed by vascular perfusion. Spaced serial sections were used to evaluate muscle fiber morphology along the length of fibers, and muscle fiber areas were measured. Myonuclei and satellite cells were counted using electron microscopy. Morphological evidence supporting muscle fiber hyperplasia was observed in exercised muscles. These observations included the presence of small fibers which may signify de novo fiber formation. Myonuclear counts indicate that myonuclear density is not a primary regulator of fiber size. Satellite cell frequency was unchanged following exercise. Autoradiographic studies revealed satellite cell activation by uptake of tritiated thymidine in exercised muscles. Satellite cell activation appears to result from increased activity in exercised muscles. These findings confirm previous studies demonstrating muscle fiber hyperplasia following weight-lifting exercise, and suggest that de novo fiber formation is the major mechanism contributing to muscle fiber hyperplasia in this model. PMID- 1605385 TI - Penetration of the uterine epithelial basement membrane during blastocyst implantation in the mouse. AB - For many species, blastocyst implantation is associated with a reduction in the number of cellular and extracellular matrix layers which separate the trophoblast from maternal vasculature. Following loss of uterine epithelial cells along the distal mural trophoblast, the mouse blastocyst encounters the residual epithelial basement membrane. This sheet of extracellular matrix must be breached and later removed prior to trophoblast invasion of the uterine stroma and formation of the placenta. The interactions between the trophoblast, luminal epithelial basement membrane, and decidual cells during the time when embryonic and uterine stromal cells first achieve contact were examined in this study. Distal mural trophoblast of activated delay blastocysts was in contact with the residual luminal epithelial basement membrane 36 hr after estrogen administration. This portion of the basement membrane contained areas in which the usual linear appearance was changed to an irregular, tortuous profile. The lamina densa frequently appeared flocculent and diffuse. Cytoplasmic processes from trophoblast and decidual cells simultaneously perforated the basement membrane at multiple discrete loci. With further development the basement membrane was lost, leaving trophoblast and decidual cells in close contact over large areas. In normally implanting blastocysts a similar stage of embryonic development, as described above, was attained by 0400 hr on day 6 of pregnancy. Regions of convoluted epithelial basement membrane were also seen in these implantation sites. However, only decidual cell processes were seen penetrating the residual basement membrane. These processes extended to the fetal side of the basement membrane and separated that matrix from overlying trophoblast. They contained organelles and formed rudimentary intercellular junctions with the trophoblast.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605386 TI - Structural differentiation of the epithelial cells of the testicular excurrent duct system of rats during postnatal development. AB - The light and electron microscopic appearance of the various epithelial cells lining the efferent ducts and different regions of the epididymis were examined in rats on postnatal days 21, 39, 49, 56, and 90 to determine the role of androgens and/or spermatozoa, as well as other possible factors, on the structural differentiation of these cells. Five conclusions may be drawn from the observations made. First, on day 21 epithelial cells of all regions are structurally undifferentiated. Second, it was not until day 49 that nonciliated cells of the efferent ducts resembled those of adult animals, suggesting that more than one factor, such as androgens, testicular products, and/or spermatozoa, is needed for their full structural differentiation. Third, principal cells of the epididymis become structurally differentiated by day 39, i.e., these cells contained an elaborate Golgi apparatus, endoplasmic reticulum cisternae, and numerous 200-400 nm electron lucent secretory vesicles, as well as a full complement of endocytic organelles; this occurred in spite of the absence of spermatozoa in the epididymal lumen. The differentiation of these epididymal cells may be under the influence of androgens, which are known to be high at this time, but may also be due to specific secretions from Sertoli cells secreted directly into the efferent ducts. Fourth, clear cells of the cauda epididymidis are fully differentiated by day 39. The presence of degenerating germ cells in the lumen of the cauda epididymidis and various cellular debris, as well as high androgen levels, may be factors causing the differentiation of the cells of this region. Finally, clear cells of the corpus and cauda epididymidis only become fully differentiated by day 49, at a time when spermatozoa appear in the lumen, despite high levels of androgens at day 39; this observation indicates that the presence of spermatozoa in the lumen may be a necessary factor in causing their differentiation. Overall, these results suggest that a combination of different factors are necessary for the structural differentiation of the various epithelial cell types of the different regions of the epididymis. PMID- 1605387 TI - Comparative anatomy and phylogeny of the cloacae of salamanders (Amphibia: Caudata). IV. Salamandridae. AB - Cloacae were examined from male and female salamanders representing 12 genera and 22 species in the Salamandridae. All female salamandrids possess numerous sperm storage glands, spermathecae, in the roof of the cloaca, but intergeneric variation exists in the occurrence of additional cloacal glands. Pleurodeles and Tylototriton possess both vent and anterior ventral glands, and secondary loss has occurred of vent glands in all other genera and anterior ventral glands in Chioglossa, Cynops, Paramesotriton, and Triturus The most highly derived cloaca occurs in Euproctus asper, in which the cloacal tube extends through a conical projection, and ventral glands secrete onto the dorsolateral surface of the projection rather than into the cloaca. Marked intergeneric variation occurs in males in conformation of the cloacal cavities and in extent of the dorsal gland. In Cynops, Euproctus, Pachytriton, Paramesotriton, Taricha, and Triturus, the pseudopenis (a broad, posteriorly projecting evagination of the dorsal roof) fills much of the cavity of the anterior cloacal chamber. In most salamandrids, distal ends of the dorsal glands occur lateral to pelvic glands in the anterior end of the cloaca, and dorsal gland tubules descend to secretory sites at the posterior end of the vent. Salamandra and Mertensiella possess a unique, bifurcated dorsal gland in which distal ends of tubules lie dorsal to the other cloacal glands, and proximal ends curve ventrally in the anterior end of the cloaca to secretory sites along the cloacal orifice. Cladistic analyses indicate that the variation in presence of anterior ventral glands is due to homoplasy. The occurrence of female vent glands, bifurcated dorsal glands, and the pseudopenis supports a phylogeny based upon non-cloacal characters. PMID- 1605388 TI - Partitioning of the Golgi apparatus in rat primary and secondary spermatocytes during meiosis. AB - We examined the disassembly and reformation of the Golgi apparatus as a function of the cycle of the seminiferous epithelium in adult rats during stages XIII and XIV, i.e., just prior to and during meiosis I and II. Serial section analysis of primary spermatocytes at metaphase I demonstrated the presence of two Golgi complexes. At the ultrastructural level, these Golgi complexes were shown to be composed of stacks of cisternae and vesicles, with each stack having a varying number of saccules. Although Golgi complex intermediates resulting from the process of organelle disassembly were not clearly identified in diplotene spermatocytes immediately prior to nuclear envelope vesiculation, we did observe clusters of vesicles resembling the "nuage," with each cluster varying in size and number of vesicles. Meiosis I results in the formation of secondary spermatocytes that exhibit a well-formed spherical Golgi complex approximately half the size of the diplotene spermatocyte Golgi. Next, secondary spermatocytes enter meiosis II. In contrast to metaphase I, during metaphase II reformation of the Golgi apparatus into stacks was not observed and only small clusters of vesicles at two poles of dividing cells were detected. In addition, "nuage"-like structures were not identified during meiosis II. Our results begin to characterize the process by which Golgi apparatus partitioning is accomplished during meiosis, presumably resulting in the delivery of equal complements of this organelle to four round spermatids. We suggest that partitioning of the Golgi apparatus takes place prior to metaphase I and that the two steps of meiosis may exhibit subtle differences with respect to Golgi partitioning. PMID- 1605389 TI - Cell kinetics of lamina propria fibroblasts in normal adult hamster bronchus. AB - Forty-nine 12-week-old male Syrian golden hamsters (Mesocricetus auratus), weighting 108 to 128 g, were injected i.p. with [3H]-thymidine (3HTdR 2 microCi/g body wt). Animals were divided into 7 weight-matched groups and were killed at 1 hour (day zero) and 1, 2, 3, 4, 7, and 14 days after thymidine injection. Lungs were fixed by vascular perfusion of 4% formalin/1% glutaraldehyde in 0.2 M cacodylate buffer at pH 7.4, cut at 2 microns, dipped in Kodak NTB3 or NTB2 nuclear emulsion, exposed for 2 weeks, developed and stained. In each airway cross-section, total epithelial and fibroblast counts and labeled cell count were estimated. A cell was considered labeled when 3 or more silver grains appeared on its nucleus. The background grain count was less than 1 grain per nucleus. Mean epithelial and fibroblast cell density in a 100 microns segment were respectively 14.8 +/- 0.1 and 6.6 +/- 0.1 cells (the second number is one standard error of the mean). One hour after labeling, their respective labeling indices (L.I.) were 0.13 +/- 0.02 and 1.24 +/- 0.1. On day 1, their L.I. doubled and then returned to the initial value. One hour after labeling, epithelial and fibroblast mean grain counts did not differ significantly. They were respectively 20.6 + 1, and 15.8 +/ 2. Because grain count intensity is closely related to DNA synthetic time, it seems plausible that epithelial and fibroblast synthetic times do not differ much. Cell turnover and cell cycle times were estimated from grain count dilution curves.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605390 TI - Cell renewal and gene expression in the trachea of hamster at different ages. AB - The tracheal mucosa of the Syrian golden hamster has been extensively employed as a model system for respiratory tract cell renewal, injury, and carcinogenesis. However, baseline cell kinetic data are not available for normal juvenile and adolescent animals in which the mucosa and cartilage are rapidly enlarging. The objective of this research was to elucidate alterations in cell kinetics, epithelial morphology, and gene expression in the trachea of hamsters at different ages. Cell kinetics were examined by 3H-thymidine labeling indices, morphology by light and electron microscopic examination, and gene expression by slot blot analysis. Results showed that mucosal epithelium of the young and adolescent hamster undergoes cyclic necrosis and cell shedding, exposing portions of the elastic basal lamina. Epithelial shedding was associated with hyperplasia and squamous metaplasia. Additionally, the labeling indices of mucosal epithelial cells and chondroblasts also exhibited variable patterns which were associated with a cyclic pattern of expression of c-fos and c-erbB2 proto-oncogenes and epidermal growth factor receptor. PMID- 1605391 TI - Supra-neuroectodermal cells and fibers on the primary nasal cavity and in the fourth ventricle of mouse and human embryos: scanning and transmission electron microscopic studies. AB - Neuroectoderm-derived epithelia of the primary nasal cavity and the fourth ventricular floor and roof were observed by scanning (SEM) and transmission electron microscopy (TEM) and SEM-TEM correlative views in mouse embryos of 9th to 13th days of gestation, and in 38 externally normal human embryos ranging at Carnegie stages from 13 to 18 (about 5 to 7 weeks of gestation). Smooth-surfaced spindle-shaped cells with one or more cytoplasmic processes and cord-like cytoplasmic structures were observed by SEM on the wall of the primary nasal cavity of both species. They had morphological features similar to those of neuronal type 1 supraependymal (SE) cells and SE fibers on the floor and roof of the fourth ventricle in both species. Type 1 SE cells, SE fibers, and corresponding structures in the primary nasal cavity were localized in relation to the underlying developing nerve and vascular systems. Furthermore, their processes and fibers ran roughly parallel to these underlying structures and they penetrated the epithelial layer at the ends, suggesting a connection with underlying structures. From TEM and SEM-TEM correlative observations, SE fibers in the fourth ventricle and cord-like structures in the primary nasal cavity, both with a larger diameter, were deduced as single axon-like processes or bundles of processes. Those fibers and cord-like structures of smaller diameters were interpreted as elongated telophase bridges; both contained parallel packed microtubules and connected distant cells. Since these processes and fibers were generally longer and became fewer at later developmental stages, they appeared to be transient neuronal structures. They may play a development-related role in such morphogenetic cell movements as in the developing nerve and vascular systems in the epithelial and/or subepithelial layers, but not as direct rudiments of adult nerve tissues. PMID- 1605392 TI - Morphological and mapping studies of the paranodal and postnodal levels of the neural plate during chick neurulation. AB - The morphology of the paranodal and postnodal levels of the neural plate as well as the fate of its cells was examined in chick embryos at stages 3-11. The morphology of the paranodal and postnodal levels of the neural plate closely resembles that of the prenodal neural plate. Furthermore, during shaping and bending of the neural plate, these levels undergo changes similar to those of the prenodal level. In short, the paranodal and postnodal levels of the neural plate consist of a pseudostratified columnar epithelium that thickens dorsoventrally and narrows mediolaterally and then undergoes localized furrowing and folding. Fate mapping revealed that at mid-neurula stages, the prospective hindbrain and spinal cord levels of the neuraxis flank the primitive streak. Hensen's node moves caudally with respect to these future neuraxial levels as it regresses during the latter stages of gastrulation. Cells of the medullary cord, the rudiment of the secondary portion of the neural tube, arise in the vicinity of the cranial portion of the primitive streak, near the caudal end of the postnodal levels of the neural plate. Thus, during stages of gastrulation and primary neurulation, the precursor cells of the primary and secondary portions of the neural tube (spinal cord) lie in close proximity to one another. This study provides new information on the morphology and extent of the paranodal and postnodal levels of the neural plate, the changes these areas undergo during shaping and bending of the neural plate, and the contributions of its cells to the primary and secondary levels of the neural tube, increasing our understanding of the complex events underlying avian gastrulation and neurulation. PMID- 1605393 TI - Studies on wound healing in the neuroepithelium of the chick embryo. AB - Wound healing has been studied by light microscopy, SEM, and TEM in the neuroepithelium of the early neurula (stages 6 and 8) and advanced neurula (stages 10 and 12) chick embryos. Healing involves two major events: (1) apposition of the wound edges and (2) restitution of the neuroepithelium at the wound site (i.e., restoration of the epithelial integrity of neuroepithelium). Apposition of the wound edges occurs within the first 15 minutes of re-incubation and involves the entire length of the wound. The main event during restoration is a change in the shapes of the rounded cells to elongated forms (i.e., spindle, wedge, and inverted wedge shapes). Wounds of younger embryos heal faster than those of older ones. PMID- 1605394 TI - Anatomical and immunohistological demonstration of the primary neural connections of the vomeronasal organ in the dog. AB - Macro- and microdissection methods together with conventional histology and lectin immunohistochemistry have been used to identify the course of the vomeronasal nerves and their site of termination (accessory olfactory bulb; AOB) in the dog. The AOB in this species is small and variable in size, situated on the medial surface of the main olfactory bulb, and has an anatomical structure unlike that described for other mammals. The vomeronasal nerves and their terminal glomeruli in the AOB are easily identifiable by selective immunohistochemical staining using Ulex europeus agglutinin I. PMID- 1605395 TI - Skeletal malformations in hatchery reared Rana perezi tadpoles. AB - Skeletal malformations at metamorphosis in Rana perezi tadpoles reared in culture have been studied. Tadpoles were fed ten artificially compounded and fresh diets and kept at two different temperatures. Animals were maintained in fiberglass tanks. Bone damages are related to the nourishment with compound diets. Tadpoles fed such diets showed variable percentages of scoliosis, kyphosis, luxations, and subluxations in the hind limbs, aplasia in phalanges, and wide failures of ossification. The data suggest the origin of the lesions is a deficiency in some compounded diets that could alter collagen metabolism during skeletal adjustments at metamorphosis. PMID- 1605396 TI - A new look at the blood supply of the retro-ocular space. Three-dimensional analysis of the arterial pattern of the posterior ciliary artery. AB - A study of the arterial architecture of the orbit, especially the ophthalmic artery and the course of the posterior ciliary artery in the retroocular space, was carried out in 198 cadavers by three-dimensional arteriographic analysis. The posterior ciliary arteries were classified into three types: lateral posterior ciliary, medial posterior ciliary, and accessory posterior ciliary arteries. Both the lateral and medial posterior ciliary arteries reach the eyeball in three ways: (1) they run antero-inferiorly in a winding course to the posterior margin of the eyeball, then shift upward vertically at a 60-90 degree angle and reach the eyeball, where they divide into several ciliary branches (69%); (2) after a similar course, others branch to the eyeball from the superior side (29.3%); or (3) they reach the eyeball in an almost straight course along the optic nerve (1.7%). The fundamental characteristics of these three types of posterior ciliary artery pattern also exist in subhuman primates. PMID- 1605397 TI - Detailed anatomy of the antebrachiocarpal joint in dogs. AB - A comparative study of the anatomy of the antebrachiocarpal (AC) articulation was carried out in 30 adult dogs with 60 joints. Although a considerable degree of similarity was found between the AC joint in dogs and the corresponding wrist joint in humans, a number of differences between these two homologous joints were also noted. The distal end of the ulna in dogs directly articulates with the ulnar carpal and accessory carpal bones forming a specialized antebrachiocarpal arrangement more adapted to running. The accessory carpal bone in dogs is a massive, long bone and is strikingly different from its homologue in humans, the pisiform bone. The joint between the accessory and ulnar carpal bones, which corresponds to the piso-triquetral joint in humans, is always connected with the AC joint, whereas in humans this communication could be found occasionally. The large radial carpal bone in dogs, characteristic for carnivores, corresponds to the fused scaphoid and lunate bones in humans, in whom this type of fusion is very rarely found. The palmar ulnocarpal and radiocarpal ligaments in dogs are distinctly intra-articular, whereas in humans these ligaments are intracapsular. One of the controversies of the AC joint in dogs is a structure located between the distal-most parts of the radius and ulna forming a strong bond between these two bones and a part of the antebrachial articular surface. It is cartilage-like and is composed of typical fibrocartilaginous tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605398 TI - Evaluation of spermatozoa of the rat in hyperprolactinaemia induced by metoclopramide. AB - Metoclopramide (MCP) in doses of 2.2 mg kg-1 body weight, being administered intraperitoneally to rats for 14 d, provokes a premature release of germ cells in the testes. The number of spermatozoa is reduced. In addition the spermatozoa exhibit defects of head and tail structures. After the administration of MCP for 14 d, followed by a 14-d break in applying the drug, the number of spermatozoa in the lumen of the epididymal duct continues to be low. Many spermatozoa are damaged. Only after a 66-d-break in MCP administration is the morphology of the seminiferous epithelium restored, and a large number of spermatozoa appear in the lumen of the epididymal duct. PMID- 1605399 TI - Integration of new regulatory strategies into the network of an endocrine control system: limitation of androgen secretion by rat testis is achieved by substrate dependent modulation of P450XVII enzyme concentration and catalytic efficiency. AB - In addition to the well-known control circuits involved in the regulation and adaptation of testicular androgen biosynthesis, it is proposed that two new control strategies are involved in the maintenance of steady-state testosterone secretion rates by testicular Leydig cells. Cytochrome P450XVII (steroid-17 alpha monooxygenase/steroid-17,20-lyase), one key enzyme in steroid hormone biosynthesis, responds to external human choriogonadotropin stimulation with an oxygen-dependent and substrate flux-dependent inactivation and decomposition, and increased substrate availability decreases the efficiency of androgen formation in favour of abortive intermediate leakage. These results are discussed as a paradigm of substrate-dependent modulation of cytochrome P450 activities. PMID- 1605400 TI - Effect of flutamide on the physiological status of epididymis and epididymal sperms. AB - Flutamide, a pure antiandrogen, increases the levels of plasma luteinizing hormone but antagonizes the biological expression of androgen on target organs. Flutamide was administered to rats to study the effect of altered availability of hormones on the functional status of epididymis. The weights of ventral prostate, seminal vesicles and epididymis showed antiandrogenic effects of flutamide. However, increased activity of kidney beta-glucuronidase reflected increased availability of testosterone. The concentrations of protein and DNA along with the activities of acid phosphatase and hyaluronidase decreased in flutamide treated rats. The activities of acid phosphatase and hyaluronidase in epididymal sperms along with protein concentration increased in flutamide-treated rats. Alteration of epididymal function by treatments affecting lysosomal stability was indicated. PMID- 1605401 TI - Gynaecomasty as the first manifestation of sexual precocity (case report). AB - We report on a young boy who developed gynaecomastia 15 months before he showed clinical manifestations of sexual precocity. He was treated with medroxyprogesterone acetate with good results. His development to adulthood is presented. The causes of gynaecomastia in the prepubertal child are reviewed. PMID- 1605402 TI - Quantitative morphology of the testicular tubular epithelium in the water buffalo (Bubalus bubalis). AB - Ultrastructural features and morphometric evaluations of water buffalo seminiferous epithelium are reported for the 6 phases of the spermatogenic cycle. The relative Sertoli cell volume varies between 30% (phase 4) and 39% (phase 8), the calculated volume of a Sertoli cell between 7118 microns3 and 8968 microns3 (phase 4). Smooth ER is the organelle that exhibits the most prominent changes in Sertoli cells during the spermatogenic cycle: it occupies about 6% in phase 3 and 21% in phase 4. All spermatogenic cells of the same clone present cytoplasmic bridges among them. From preleptotene (about 470 microns3) to late diplotene (about 2300 microns3) the volume of a primary spermatocyte increases nearly 5 fold; their nuclear volumes increase 3.5-fold in the same period. Secondary spermatocytes are found only in phase 4 of the cycle. Due to partial cell necrosis and autolysis late maturation phase spermatids display not more than 25% of the size of early cap phase spermatids. 63% of all numerically possible germ cells disappear from the seminiferous epithelium during spermatogenesis. Particularly heavy cell loss is observed in phase 4 and involves the spermatogonial fraction as well as cells during the second meiotic division. PMID- 1605403 TI - No change in acrosome reaction of human spermatozoa during storage in cervical mucus. AB - Incubation of human spermatozoa in capacitation media for 24 h results in a significant increase in acrosome reacted spermatozoa as compared to preincubation (baseline) levels. By contrast, sperm samples recovered from the cervix for as long as 72 h after coitus only showed baseline percentage of acrosome reacted spermatozoa. These results indicate that spermatozoa do not undergo the acrosome reaction during cervical storage and suggest that cervical mucus suppresses the spontaneous acrosome reaction of spermatozoa that become capacitated in the cervix. PMID- 1605404 TI - Hyperprolactinaemia and hyperserotoninaemia: their relationship to seminal quality. AB - Seminal quality and levels of blood serotonin (5-HT) and serum prolactin (PRL) were determined in 60 men attending an infertility service. Subjects were grouped according to normal or abnormal accessory sex gland function. Subjects with normal accessory sex gland function were further subdivided into groups with asthenozoospermia, polyzoospermia, normozoospermia, oligozoospermia, or azoospermia. Blood 5-HT levels were significantly higher in oligozoospermics (115.9 +/- 23.7 ng ml-1, P less than 0.05), and asthenozoospermics (90.0 +/- 8.2 ng ml-1, P less than 0.05), than in normals (68.5 +/- 5.3 ng ml-1), whereas serum PRL levels were higher in azoospermics (44.2 +/- 4.7 ng ml-1) than in normozoospermics (15.9 +/- 1.6 ng ml-1, P less than 0.01). Subjects with abnormal accessory sex gland function were also subdivided according sperm count and sperm motility categories. None of these subgroups showed differences in serum PRL levels or blood 5-HT levels. Men with hyperserotoninaemia had higher serum PRL levels, low sperm count, and low motile sperm concentration. Moreover, higher 5 HT levels may be observed in men with normal PRL levels and also associated with normal PRL levels and with hyperprolactinaemia, and hyperprolactinaemia may be observed also associated with normal serotonin levels. Hyperserotoninaemia was related to both diminished sperm count and sperm motility, whereas hyperprolactinaemia was related to low sperm count. When hyperprolactinaemia and hyperserotoninaemia were both present, additive effects were observed. PMID- 1605405 TI - [Value of immunocytochemical analysis of dystrophin in the diagnosis of X chromosome linked muscular dystrophy]. PMID- 1605406 TI - [Nocturnal use of pirenzepine by a group of insulin dependent juvenile diabetics]. AB - Different studies have shown an elevation of GH levels in insulin-dependent diabetic adults and its modification after pirenzepine administration. We have studied nocturnal GH secretion (NIGHS) and fructosamine levels before and after one month of administering a nocturnal dose of pirenzepine [Gastrozepin (R.) 0.6 mg/kg] in a group of eight young insulin-dependent diabetics, 6 males and 2 females. The ages of the subjects ranged between 12 and 17 years with a mean age of 15.28 years. The most important findings were: 1) The NIGHS was not modified by pirenzepine administration, 10.88 +/- 3.81 ng/ml/min vs 11.25 +/- 7.90 ng/ml/min, p greater than 0.05. However, two patients showed a clear decrease in their G.H. levels. 2) Plasma fructosamine levels were also unaffected, 409 +/- 101 mmol/l vs 361 +/- 127 mmol/l, p greater than 0.05. However, the levels of five individual patients decreased after pirenzepine administration. We conclude that oral pirenzepine administration at this dose does not modify GH secretion nor improve short term metabolic control of the disease in young insulin dependent diabetics. Further investigation, using higher doses and for a more prolonged period of time, is necessary to know the long term effects of this treatment. PMID- 1605407 TI - [Prevalence of iron deficiency and iron deficiency anemia in infancy and related factors in a community of the Murcia region]. AB - In this study of 98 children, we determined hematological values and serum iron concentrations. A nutritional investigation was also done. We found that 25.5% of the children were iron deficient and 12.2% were anemic. In the group of children with iron deficiency, the introduction of meat and cereals was significantly late (p less than 0.01 and p less than 0.05, respectively). In this same group of children the introduction of whole cow milk was earlier, although not significant (NS). The age of maximal prevalence was between 13 and 24 months. These results indicate a need to screen for iron deficiency during the second year of life, to delay the introduction of whole cow milk and not to delay the introduction of meat and cereals. PMID- 1605408 TI - [Cytogenetic study of a family with 15p+ chromosomal plymorphism]. AB - This cytogenetic study deals with a family in which some members are carriers of 15p+ polymorphism variant, with an unusually elongated short arm. The chromosomal marker segregates in three generations, duplicating its length but without phenotypic manifestation in the carriers. An analysis by using banding techniques shows us the characteristics of the p+ region and its transmission within the family. PMID- 1605409 TI - [Importance of molecular diagnosis in the detection of healthy male transmitters of the fragile X syndrome]. AB - The fragile X syndrome is attracting much interest because it is now recognized as the most common genetic cause of mental retardation after Down's syndrome. No effective treatment is yet available and the underlying biochemical defect is not understood. Genetic counselling is often difficult because, although it primarily affects males, one third of carrier females are also retarded. In addition, there is an important percentage of males that inherited the mutation and appear phenotypically normal. These observations have prompted extensive clinical, epidemiological and genetic studies. The more relevant points are reviewed in light of our results. PMID- 1605410 TI - [Nutritional study of children with oncologic diseases]. AB - From October 1989 to June 1990 we have evaluated at diagnosis and after six months of treatment the nutritional status of 21 oncologic patients younger than 14 years. At diagnosis, 14% of the children showed slight malnutrition on anthropometric evaluation, although there were biochemical data of protein malnutrition in 47% of the cases. Children with abnormal anthropometric measurements and those with a high risk of becoming malnourished (infants with advanced abdominal diseases) were given dietary supplements. In the follow-up evaluation, 90% of the patients showed normal somatic indexes and 76% showed recuperation in their protein values. The recovery of the nutritional status was most important in the group of patients with Acute Lymphoblastic Leukemia. PMID- 1605411 TI - [Biliary lithiasis in childhood]. AB - We have reported 28 cases of pediatric cholelithiasis in our hospital between 1980 and 1990. We found risk factors in 15 of these cases (53.6%). The most frequent risk factors were hereditary spherocytosis, cholestasis and obesity. A high frequency of non-hemolytic cholelithiasis was noted. Lithiasis was a casual finding in 13 cases (46.4%). The most frequent symptom was nonspecific abdominal pain, which occurred in 8 patients. Diagnosis was made with echography in every case. The range of time in which the patients were followed ranged between 1-5 years. Eight children required surgery. Among the other twenty, twelve were asymptomatic and six improved spontaneously. The mean age at the moment of diagnosis was younger in the children that spontaneously recovered than in children with permanent lithiasis. Therefore, for this reason, we recommend an observation period before surgery in children younger than 3 years of age. PMID- 1605412 TI - [Ureaplasma urealyticum and Mycoplasma hominis: incidence and clinical significance of their isolation in the perinatal period]. AB - In order to known the clinical significance of the colonization of the maternal genitalia and infant with genital mycoplasmas, we studied prospectively 219 pairs of mothers and newborns admitted for delivery to a general public hospital. U. urealyticum and M. hominis were isolated from 72 (32.9%) and 10 (4.6%) of the mothers, respectively. During the first 4 days of life. U. urealyticum and M. hominis were isolated from 23 (10.5%) and 1 (0.5%), of the newborn infants respectively. Maternal colonization by genital mycoplasmas was not associated with a longer duration of membrane rupture, nor with a shorter gestational age, nor with smaller neonatal weight and length. Neonatal colonization by U. urealyticum was not associated with shorter gestational age, nor with smaller birth weight and length, nor with the appearance of any disease during the first 3 months of life. PMID- 1605413 TI - [Evolution and treatment of 19 cases of pertussis in infants under 4 months of age]. AB - We present 19 cases of pertussis in infants under 4 months of age. In all cases, Bordetella pertussis was isolated from nasopharyngeal swabs. A whooping cough, cyanotic episodes and eating disturbances were the most characteristic clinical findings. Treatment included: supportive care, salbutamol, beclomethasone, and josamycin. Lymphocyte counts higher than 40,000/mm2 were associated with a greater severity of illness. The most frequent complications were: recurrent cough and pneumonia. None of the patients died. PMID- 1605415 TI - [Epidemiology of respiratory syncytial virus infections in the Canary Islands]. AB - Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in young children. Outbreaks of RSV infection occur yearly during the winter or spring in temperate climates. Our study of 634 hospitalized children under 3 years of age with bronchiolitis and pneumonia (November 1988 to January 1990) revealed that 227 (35.8%) had VRS infections. These cases showed a yearly epidemic pattern with 86.8% of the cases occurring during the winter. Furthermore, 67.4% of the cases occurred in children between 1-6 months of age and the boy/girl ration was 1.2/1. In 26.9% of the infections there was an antibody response. These results for RSV infection on this island show the same epidemiological pattern as that in the temperate climates. PMID- 1605414 TI - [Sero-epidemiologic study of measles, rubella and mumps in the infantile population of Salamanca]. AB - A seroepidemiological study, including a interview-questionnaire, was carried out in a representative sample of children from Salamanca (Spain) between the ages of 15 months and 7 years. The objective of this study was to know the vaccination level and the immune status against measles, mumps and rubella (MMR). The vaccination level with MMR-vaccine was 70%. The antibody prevalence was 84% against measles, 85.3%, against mumps and 76.7% against rubella. The number of children with antibodies against all three diseases was 66%. Nineteen percent of the children vaccinated with MMR-vaccine were susceptible to one or more of the three diseases. The administration of a second dose of MMR-vaccine may be considered necessary. PMID- 1605416 TI - [BCG scars in children vaccinated during the neonatal period in Madrid]. PMID- 1605417 TI - [Vital emergency diagnosis: cardiac tamponade related to central catheterization for parenteral nutrition]. PMID- 1605418 TI - [Isolation of Campylobacter lari (laridis) in feces from a child with acquired immunodeficiency syndrome]. PMID- 1605419 TI - [Intestinal invagination: should salt be added to the barium?]. PMID- 1605420 TI - [Systemic lupus erythematosus and pancreatitis. Apropos of a case]. PMID- 1605421 TI - [Veno-occlusive disease of the liver associated with humoral and cellular immunodeficiency]. PMID- 1605422 TI - ["Cat eye syndrome" with right renal agenesis. Report of a case and review of the literature]. PMID- 1605423 TI - [Meningitis caused by multiresistant Pneumococcus]. PMID- 1605424 TI - [Bacteremia caused by Bordetella bronchiseptica in the course of inflammatory tinea capitis]. PMID- 1605425 TI - Hospital-acquired infection with vancomycin-resistant Enterococcus faecium transmitted by electronic thermometers. AB - OBJECTIVES: To describe an epidemic of vancomycin-resistant Enterococcus faecium causing bacteremia and bacteriuria, to identify the source of infection, to delineate risk factors associated with acquisition of the organism, and to determine antibiotic sensitivities for the organism. DESIGN: Investigation of an epidemic, including a case-control study. SETTING: Medical-surgical intensive care unit and ward in a university medical center. PATIENTS: Nine patients infected or colonized with vancomycin-resistant Enterococcus faecium and 20 noninfected controls. MEASUREMENTS: Clinical data, environmental surveillance cultures, and in-vitro microbiologic studies. RESULTS: Colonization or infection by vancomycin-resistant E. faecium was associated with an increased duration of treatment with ceftazidime, 13.2 compared with 4.6 days, and a greater number of nonisolated days of hospitalization in the intensive care unit, 19.9 compared with 6.4 days for infected and noninfected patients, respectively (P less than 0.05). Environmental surveillance cultures recovered the organism repeatedly from the rectal probe handles of three electronic thermometers used exclusively on nonisolated patients in the intensive care unit. Restriction endonuclease analysis of plasmid DNA showed that all clinical and environmental isolates were identical. Infection control measures, including isolation of colonized or infected patients and removal of the rectal thermometer probes suspected to be responsible for transmission, resulted in termination of the outbreak. In-vitro, time-kill studies showed that the combination of ciprofloxacin, rifampin, and gentamicin resulted in bactericidal activity against the organism. CONCLUSIONS: This nosocomial outbreak of infection due to a highly vancomycin-resistant strain of Enterococcus is the first epidemic in which an electronic thermometer has been implicated as the vehicle of transmission for an infectious agent. PMID- 1605426 TI - The clinical course of idiopathic dilated cardiomyopathy. A population-based study. AB - OBJECTIVE: To describe the prognosis of individuals with idiopathic dilated cardiomyopathy in a population-based sample and to compare this with the prognosis of patients in a previous referral center case series of idiopathic dilated cardiomyopathy. DESIGN: Cohort study. SETTING: Population-based in Olmsted County, Minnesota. PATIENTS: Forty residents of Olmsted County, Minnesota with idiopathic dilated cardiomyopathy initially diagnosed between 1975 and 1984 who were followed through 1 July 1989 and 104 patients from a Mayo Clinic referral case series from 1960 to 1973. MEASUREMENTS: Survival for the population based cohort at 1 year and 5 years. RESULTS: Survival at 1 year differed dramatically between the population-based cohort and the referral case series at 1 year (95% compared with 69%, respectively) and at 5 years (80% compared with 36%, respectively) (P less than 0.001). Long-term survival for the population based cohort was nonetheless impaired when compared with an age- and sex-matched cohort, that is, the 1980 Minnesota white population (8-year survival: observed, 58% compared with expected, 83%; P less than 0.001). Among community patients, older age (adjusted Cox model hazard ratio for 10-year increase in age, 1.59; 95% CI, 1.08 to 2.35) and lower left ventricular ejection fraction (adjusted hazard ratio for 10% decrease, 1.90; CI, 1.04 to 3.50) were independently associated with impaired survival. CONCLUSIONS: These population-based data challenge the clinical perception of the clinical course of idiopathic dilated cardiomyopathy based on referral practice prognostic studies and suggest that the clinical course of this condition may be more favorable than previously recognized. PMID- 1605427 TI - Hepatitis after germander (Teucrium chamaedrys) administration: another instance of herbal medicine hepatotoxicity. AB - OBJECTIVE: To show that germander (Teucrium chamaedrys), an herbal medicine used to facilitate weight loss, may be hepatotoxic and to delineate the nature of the injury. DESIGN: Retrospective study. SETTING: Liver units of several centers in the French Network of Pharmacovigilance. PATIENTS: Seven patients who developed hepatitis after germander administration and who had no other cause of liver injury. MEASUREMENTS: Clinical examination, liver function tests, various serologic tests, ultrasonography, and histologic study. RESULTS: Hepatitis characterized by jaundice and a marked increase in serum aminotransferase levels occurred 3 to 18 weeks after germander administration. Liver biopsy specimens in three patients showed hepatocyte necrosis. After discontinuing treatment with germander, jaundice disappeared within 8 weeks and recovery was complete in 1.5 to 6 months. In three cases, germander readministration was followed by the prompt recurrence of hepatitis. CONCLUSION: Germander may be hepatotoxic, which supports the view that herbal medicines are not always as safe as generally assumed. PMID- 1605428 TI - Spectrum bias in the evaluation of diagnostic tests: lessons from the rapid dipstick test for urinary tract infection. AB - OBJECTIVE: To determine if the leukocyte esterase and bacterial nitrite rapid dipstick test for urinary tract infection (UTI) is susceptible to spectrum bias (when a diagnostic test has different sensitivities or specificities in patients with different clinical manifestations of the disease for which the test is intended). DESIGN: Cross-sectional study. PATIENTS: A total of 366 consecutive adult patients in whom clinicians performed urinalysis to diagnose or exclude UTI. SETTING: An urban emergency department and walk-in clinic. MEASUREMENTS: After the patient encounter, but before dipstick test or culture was done, clinicians recorded the signs and symptoms that were the basis for suspecting UTI and for performing a urinalysis and an estimate of the probability of UTI based on the clinical evaluation. For all patients who received urinalysis, dipstick tests and culture were done in the clinical microbiology laboratory by medical technologists blinded to clinical evaluation. Sensitivity for the dipstick was calculated using a positive result in either leukocyte esterase or bacterial nitrite, or both, as the criterion for a positive dipstick, and greater than 10(5) CFU/mL for a positive culture. RESULTS: In the 107 patients with a high (greater than 50%) prior probability of UTI, who had many characteristic UTI symptoms, the sensitivity of the test was excellent (0.92; 95% CI, 0.82 to 0.98). In the 259 patients with a low (less than or equal to 50%) prior probability of UTI, the sensitivity of the test was poor (0.56; CI, 0.03 to 0.79). CONCLUSIONS: The leukocyte esterase and bacterial nitrite dipstick test for UTI is susceptible to spectrum bias, which may be responsible for differences in the test's sensitivity reported in previous studies. As a more general principle, diagnostic tests may have different sensitivities or specificities in different parts of the clinical spectrum of the disease they purport to identify or exclude, but studies evaluating such tests rarely report sensitivity and specificity in subgroups defined by clinical symptoms. When diagnostic tests are evaluated, information about symptoms in the patients recruited for study should be included, and analyses should be done within appropriate clinical subgroups so that clinicians may decide if reported sensitivities and specificities are applicable to their patients. PMID- 1605429 TI - Proarrhythmia in patients treated for atrial fibrillation or flutter. AB - OBJECTIVE: To review data on the type, mechanism, and prevalence of the proarrhythmic effect of drugs used to treat atrial fibrillation or flutter. DATA SOURCES: English-language literature from the early 1960s to the present was identified by manual search of the literature; relevant articles were reviewed. Pertinent earlier studies were identified from references in the articles reviewed and were included when relevant. STUDY SELECTION: All studies, controlled and uncontrolled, as well as individual case reports that contained data convincingly linking atrial antiarrhythmic therapy to a proarrhythmic side effect were included. DATA EXTRACTION: Key data were extracted from each article in studies in which a causal relationship between the use of a drug and a proarrhythmic response appeared likely. DATA SYNTHESIS: Antiarrhythmic therapy aimed at stabilizing the atrium may have adverse effects on the ventricle including torsade de pointes and, less commonly, sustained ventricular tachycardia. Different antiarrhythmic agents appear to have differing potentials for this proarrhythmic response, which is most common with class 1A agents. Other proarrhythmic responses to atrial antiarrhythmic agents include the acceleration of the ventricular response either by enhancing atrioventricular nodal or bypass tract conduction or by converting atrial fibrillation to flutter with 1:1 conduction. Calcium-channel blocking agents and, less commonly, digoxin may perpetuate the duration of paroxysmal atrial fibrillation, and virtually all agents can cause sinus node dysfunction or atrioventricular block. CONCLUSIONS: Although drug therapy for atrial fibrillation or flutter is generally well tolerated, the potential exists for uncommon but serious proarrhythmic effects. Knowledge of the risk factors and symptoms of these adverse reactions will help to further reduce this risk. PMID- 1605431 TI - Prophylaxis for toxoplasmosis in AIDS. PMID- 1605430 TI - Leukocyte reduction in blood component therapy. AB - PURPOSE: To review methods of preventing or minimizing the adverse effects associated with the transfusion of passenger leukocytes present in cellular blood components and to define groups of patients who are at risk for adverse effects. DATA SOURCES: English-language articles on transfusion medicine. STUDY SELECTION: Original reports describing the pathogenesis of leukocyte-induced adverse effects in transfusion recipients and the influence of leukocyte-reduced blood components on these effects. DATA EXTRACTION: Evaluation of the diagnosis, transfusion history, and treatment of the study patients; the methods and results of leukocyte reduction; and specific outcomes, including development of alloimmunization to leukocytes, febrile reactions to transfusion, and platelet refractoriness. DATA SYNTHESIS: Passenger leukocytes are the chief cause of alloimmunization to human leukocyte antigen (HLA) and leukocyte-specific antigens in transfusion recipients. Alloimmunization may result in febrile transfusion reactions, platelet refractoriness, and acute lung injury. Leukocytes are also the vector for transfusion-associated cytomegalovirus infection. Technologic advances in the leukocyte reduction of cellular blood components have made it possible to reduce the number of leukocytes to fewer than 10(7) per transfusion. Findings suggest that the use of leukocyte-reduced cellular blood components may minimize or prevent recurrent febrile reactions and alloimmunization to leukocyte antigens. Cytomegalovirus may not be transmitted by blood components containing fewer than 10(7) leukocytes. CONCLUSIONS: Leukocyte reduction in red blood cell and platelet transfusions using third-generation filters is indicated for selected patients who are likely to receive long-term transfusion support, to prevent recurrent febrile reactions and to prevent or delay alloimmunization to leukocyte antigens. Leukocyte-depleted transfusions may also be indicated to delay or prevent refractoriness to platelet transfusion. PMID- 1605432 TI - The myth of beneficent nature: the risks of herbal preparations. PMID- 1605433 TI - Pharmacologic stress echocardiography. PMID- 1605434 TI - Cerebral toxoplasmosis and prophylaxis for Pneumocystis carinii pneumonia. PMID- 1605435 TI - Graft-versus-host disease and liver transplantation. PMID- 1605436 TI - Chlamydia, smoking, and heart disease. PMID- 1605437 TI - Scientific rigor of economic analyses. PMID- 1605438 TI - Prince Dracula, rabies, and the vampire legend. PMID- 1605439 TI - Risk factors for amputation in patients with diabetes mellitus. A case-control study. AB - OBJECTIVE: To identify and quantify risk factors for lower extremity amputation in persons with diabetes mellitus. DESIGN: Case-control study. SETTING: A Veterans Affairs medical center. PATIENTS: Eighty patients having amputation associated with diabetes and 236 diabetic controls without limb lesions were enrolled before surgery from the 21,167 inpatient care and outpatient surgical patients seen at the Seattle Veterans Affairs Medical Center during a 30-month period. MEASUREMENTS: Selected vascular, neuropathic, environmental, health care, self care, nutritional, metabolic, lifestyle, and psychosocial risk factors were measured in all patients before surgery. RESULTS: Statistically significant risk factors identified from analysis included insufficient mean below-knee and foot cutaneous circulation (odds ratio, 161; 95% CI, 55.1 to 469); ankle-arm blood pressure index less than 0.45 (odds ratio, 55.8; CI, 14.9 to 209); absence of lower leg vibratory perception (odds ratio, 15.5; CI, 8.3 to 28.7); low levels of high-density lipoprotein (HDL) subfraction 3 less than or equal to 0.7 mumol/L (odds ratio, 4.9; CI, 2.9 to 8.3); and no previous outpatient diabetes education (odds ratio, 3.2; CI, 1.6 to 6.6). A logistic regression analysis done to control for the potentially confounding effects of age; race; socioeconomic status; diabetes duration, type, and severity confirmed these findings and added a statistically significant interaction between foot transcutaneous oxygen tension and peripheral vascular disease history. Clinical interventions to alter these risk factors were identified, including aggressive treatment of infection, diabetes education, protective footwear, and preventive footcare. CONCLUSIONS: Multiple risk factors exist along the continuum of conditions and events leading to lower extremity amputation in diabetes. Modification of certain risk factors by patients and health professionals may reduce the risk for amputation and thus decrease the human and dollar costs that accompany limb loss in this prevalent chronic disease. PMID- 1605440 TI - Current strategy in surgery for esophageal cancer. AB - Curative surgical treatment of esophageal cancer involves the complete macroscopic and microscopic removal of the tumor (R0-resection). Only by these means the prognosis can be improved. The treatment of choice for squamous cell cancer is transthoracic en-bloc esophagectomy. Preoperative risk analysis of the patient and staging of the tumor especially by endoscopic ultrasonography are mandatory. Tumors penetrating the esophageal wall (T3, T4) above the tracheal bifurcation and T4-tumors below the bifurcation should be treated preoperatively by (radio-)chemotherapy within the framework of a multimodal therapeutic approach. PMID- 1605441 TI - [Technics of esophageal exeresis for cancer]. PMID- 1605443 TI - [Esophageal cancer]. PMID- 1605442 TI - Left thoracotomy approach for resection of carcinoma of the oesophagus and cardia. AB - Oesophagogastrectomy is the best available treatment for patients with carcinoma of the oesophagus or cardia. It provides better longevity than other types of therapy and remains the standard against which combined modality treatment should be compared. Our experience with two hundred and twenty-four patients who underwent surgical exploration performed transdiaphragmatically by way of a left thoracotomy formed the basis of this report. Of these 224 patients, 201 (89.7%) underwent resection, 15 were bypassed and the remaining 5 patients were intubated. Of those resected, 79 patients required a two-rib thoracotomy. The postoperative mortality rate was 3.57%, and morbidity, mainly caused by respiratory complications occurred in 36 patients (16.1%), with no patients requiring ventilatory support. Surgical bypass without resection carried a higher mortality rate (8.3%) than those for resection (2.5%). All anastomosis were hand sewn. There were no anastomotic leaks. Adequate analgesia was provided by continuous extrapleural intercostal nerve block. Five year survival for squamous carcinoma was 36% while that adenocarcinoma was 18.7%. The left thoracotomy provides an effective method for undertaking oesophageal resections with low mortality and morbidity rates. This techniques has advantages and should be more widely used in the surgical management of patients with carcinoma of the oesophagus or cardia. PMID- 1605444 TI - Esophageal resection through a translaparotomic-transcervical approach. AB - The authors present their experience obtained from January/78 to March/90 with transhiatal esophagectomy. Two hundred and eighty-nine patients were operated on using this procedure; 171 of them underwent the operation for cancer of the esophagus, 76 for cancer of the cardia, 11 for cancer of the hypopharynx, and 31 for benign conditions. The esophageal replacement was made with stomach in 63.6% of the cases, ileo-ceco-coloplasty in 28.5%, left colon in 7.6%, jejunum in 0.3%. Cancer patients were mainly in advanced stages (stage III in 67.3% of esophageal cancer, and in 69.7% of cardial cancer). Average blood requirements for the different diseases ranged between 500 and 1,100 cc. Only 16 patients required admission in the ICU. Mean hospital stay ranged from 16.7 to 20.6 days. Surgical complications were hemorrhage (0.3%), and tracheal injury (0.6%). Overall operative mortality (at 30 days) was 5.8%, as a result of respiratory insufficiency (35.2%), pulmonary sepsis (17.8%), and others (23.5%). Long term survival at five years was 11.8% for cancer of the esophagus, 48.5% for cancer of the cardia, and 57.1% for cancer of the hypopharynx. PMID- 1605445 TI - [The short-term complications of the surgical treatment of thoracic esophageal carcinoma]. PMID- 1605446 TI - [The multimodal approach to cervical esophageal tumors]. PMID- 1605447 TI - [Severe esophageal dysplasias: what strategy to adopt?]. PMID- 1605448 TI - [20 years of surgical coronary revascularization. The importance of arterial grafts]. AB - Myocardial revascularization surgery by means of a saphenous aortocoronary by pass is in its third decennial of employment. Also if it has been proved of value in bettering the survival in various kind of anatomical lesions, and in resolving the anginal symptomatology in a majority of patients, it has been granted of a simple palliative surgical procedure in view of the evolutive characteristic of arteriosclerotic disease and of the progressive degenerations of the internal saphenous vein. The wide use of arterial transplants, internal mammary artery and gastroepiploic artery, gives these patients satisfying results. Due to the more technical complexity of its preparation and anastomosis, internal mammary artery was very late adopted by surgeons. Nevertheless it has acquired a title of noblesse demonstrating its long survival, and in the meantime has given an impulse to the use of the gastroepiploic artery. According to our experience 80% of our patients can obtain a complete revascularization using exclusively simple or sequential arterial transplants. Also if this surgery must rightly be considered a palliative one, for its long term results of survival and quality of life it shows a curative value. PMID- 1605449 TI - [The spastic pelvic floor syndrome: its diagnosis and treatment]. AB - The spastic pelvic floor syndrome, caused by a paradox contraction of the sphincteric apparatus at defaecation instead of relaxing, leads to constipation with difficult evacuation. Forty patients (15 males and 25 females, average age 49 years, age range 15-78) affected by serious chronic idiopathic constipation, underwent, at our Institute, from June 1989 to September 1990, the following instrumental examinations: anal manometry; electromyography of the pelvic floor; proctogram; intestinal transit time; anorectal endoscopy; in addition, in 6 cases at risk for colorectal cancer, left colonoscopy. Fifteen patients showed dyskinetic functioning of the voluntary sphincteric apparatus. The following diagnostic methods proved to be of fundamental importance: proctogram, which revealed failure to open of the anorectal angle at defaecation (mean values: at rest 88.93 degrees +/- 6.62; at defaecation 88.93 degrees +/- 9.44); electromyography of the pelvic floor, which showed the anomalous contraction of the external anal sphincter. These patients were treated by means of an air inflated endoampullary balloon to evoke the sensation of a stool and its subsequent expulsion. The correct evacuating function was resumed definitely in 9 patients (60%); for the remaining 6 patients, regular sessions of re-education are still necessary. The spastic pelvic floor syndrome is a major cause of constipation and requires an accurate diagnostic method of investigating the correct functioning of the recto-pelvic region by means of the above-mentioned methods.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605450 TI - [The prognostic significance of the vascular invasion of colorectal tumors]. AB - The authors report their experience about the clinical significance of the invasion of veins (BVI) in 68 patients with colorectal carcinoma, submitted to potentially curative surgery in the period 1980-1988. Every patient was screened for BVI. The tumoral spreading was differentiated into endovascular and perivascular permeation. The authors also considered the incidence and kind of BVI, the recurrence rate of the tumour and five-year survival rate. BVI was present in 33 patients (48.5%). Recurrence was observed in 22 patients (22.3%): 19 patients in the group with BVI (33 patients): 3 in the group of 35 patients without BVI. BVI was related to tumour stage, but it may be considered as an independent factor in its relationship with a poorer prognosis in patients affected by tumours in stages II or III; in fact, the patients in stage II had a poorer prognosis than those in stage III without BVI. These results suggest that BVI, as a prognostic factor, is independent from tumoral stage in determining the recurrence rate and the long term prognosis. PMID- 1605452 TI - [Total parenteral nutrition: a study of the microbial contamination of the bags and the infusion lines]. AB - The authors have examined during 60 groups of patients submitted to TPN each for a period of 10-15 days. In the first group the whole infusional set became replaced after 24 h., in the second and in the third group such replacement was done, respectively, after 48 and 72 h. The bacteriological examination of the fluid in the was always sterile 6 h. after preparation except in one case of the third group. The bacteriological examination of the terminal part of the infusional set was always negative in the first group, it was positive in the 3.33% of the cases, in the second group and in the 6.66% of the cases in the third group. The authors, consequently, believe that the infusional set has to be replaced after a period no longer than 24 h. Total parenteral nutrition: study on microbial contamination of bags and infusion lines. PMID- 1605451 TI - [The postoperative prevention of deep venous thrombosis and pulmonary embolism with defibrotide versus heparin-calcium: a randomized clinical multicenter study of 1296 patients undergoing major abdominal surgery]. AB - Postoperative thromboembolic complications do present an underestimated problem whenever their detection simply relies upon individual clinical judgement. Major abdominal operations are at increased risk of pulmonary embolism (PE) and deep vein thrombosis (DVT), mostly in advanced age, overweight subject, and in patients with cardiac or malignant diseases, or with previous venous diseases. Such patients may benefit from a peri- and postoperative prophylaxis with chemical or mechanical procedures, as a recent meta-analysis seems to suggest. In our experience, a randomized, multicentric clinical trial with defibrotide (DF) versus calcium-heparin (CH) was realized with the aim of evaluating their effectiveness and side effects in the prophylaxis of PE and DVT after major abdominal surgery; 1296 patients were randomly assigned to i.v. DF (400 mg.) or subcutaneous CH (0.2 ml. = 5000 U.I.) given one hour prior to operation and twice daily for seven days postoperatively. Definitive evaluation was carried out on 1212 patients (610 patients in DF and 602 in CH group, respectively) who completed the prophylaxis and monitoring schedule acceptably. One PE (0.16%) and 38 DVT (6.2%) were detected in DF group while 2 PE (0.33%) and 40 DVT (6.6%) were reported in CH treated patients. Post-operative blood loss was 578 +/- 150 cc. (median +/- S.E.M.) in DF group and 604 +/- 123 in CH group (p = n.s.). Wound hematoma was observed in 69 patients (5.7%): 20 (3.2%) in DF and 49 (8.1%) in CH group of patients (CHI-Square = 12.44; p = 0.0005); a significant post-operative decrease of RBC, WBC, Platelet count, and Fibrinogen was computed in both groups (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605453 TI - Endoscopic ultrasonography and esophageal cancer. PMID- 1605454 TI - [Hypoglycemia induced by oral hypoglycemic agents. Records of the French Regional Pharmacovigilance Centers 1985-1990]. AB - All 98 cases of sulfonylurea-induced hypoglycemia reported by the 30 regional drug-monitoring centers between 1985 and 1990 were analyzed: 46 with gliclazide, 40 with glibenclamide, 5 with glipizide, 1 with glibornuride and 6 with first generation sulfonylureas. These cases of hypoglycemia were often serious. The patients were 61% female and their mean age was 78.9 years. The average number of medications being taken was 3.4, but ranged up to 14. The risk factors were: reduced food intake (4.2%), renal failure (4.2%), prescription error (3.2%), voluntary or accidental overdose (5.2%), alcohol (1.1%), suspected drug interactions (50%), unknown (32.6%). The most frequent drug interactions involved miconazole (8 cases), angiotensin-converting enzyme inhibitors (9 cases), lipid regulating agents (fibrates) (7 cases), co-trimoxazole (trimethoprim sulfamethoxazole; 5 cases), metformin (4 cases), histamine H2-receptor antagonists (4 cases). The mechanisms of these interactions are discussed. PMID- 1605455 TI - [Ophthalmologic manifestations in patients under chronic hemodialysis]. AB - Ocular modifications were assessed in a prospective study carried out on 61 chronically hemodialyzed patients. Their mean age was 39.6 years (range: 7-73 yr) and the mean duration of dialysis was 30.5 months. The loss of visual acuity was especially associated with cataracts or refractive disorders. Corneal conjunctival calcifications were found in 36% of the patients and were statistically significantly correlated with the duration of hemodialysis. Eyeground modifications were observed in 36% of the subjects; 21.3% of them were hypertensive retinopathies. Cataracts were less common (5%) than small calcifications in the lens (24.5%). Conjunctival biopsies taken from two patients confirmed the presence of calcium salt deposits under the conjunctival epithelium. PMID- 1605456 TI - [Do implantable insulin pumps have a value other than experimental?]. PMID- 1605457 TI - [What is the future of the physiopathology and treatment of diabetes?. Interview by P. Youinou]. PMID- 1605458 TI - [Systemic aspects of heart myxoma]. PMID- 1605460 TI - [Anatomoclinical conference at Pitie-Salpetriere Hospital. Case 1. 1992. Polyarthritis, carpal tunnel syndrome and pain during mastication in a 60 year old clergyman]. PMID- 1605459 TI - [Subepidermal autoimmune bullous skin diseases]. PMID- 1605461 TI - [Contribution of transesophageal echocardiography in the investigation of the atrium in systemic embolism]. AB - Transesophageal echocardiography (TEE) is a semi-invasive examination that provides better images of the atrium than classical transthoracic echocardiography (TTE) due to the anatomical positioning of the captor and the high frequency Doppler apparatus used. We used TEE and TTE to evaluate the incidence of the cardiac origin of emboli in 46 patients with unexplained stroke or transient ischemic attack (TIA): 23 had documented heart disease (mean age 60 years) and 23 had no cardiac disease (mean age 43 years). Among those with existing heart disease, 4% of the anomalies certainly or probably responsible for the emboli in addition to the underlying cardiopathy were detected by TTE versus 37% by TEE (as compared to values reported in the literature: 25% by TTE and 51% by TEE). In particular, 4 abnormalities were better visualized by TEE: left atrial thrombus, especially those located in the auricle (5 TEE versus 1 TTE); spontaneous contrast showing the swirl of blood stagnating in the dilated left atria of patients with mitral valve disease seen in 7-39% of the TIA by TEE as compared to less than 1% by TTE (3 TEE versus 0 TTE); aneurysm of the interauricular septum (AIAS) observed in 5-16% of the TIA by TEE as opposed to 0 1% by TTE (4 TEE versus 1 TTE); patent foramen ovale (PFO) was noted more frequently following injection of a contrast medium when visualized by TEE (19 22%) than by TTE (6-8%) and can explain the passage of a paradoxical embolus (1 TEE versus 0 TTE). The incidences of left atrial thrombus, AIAS and PFO are well correlated with systemic emboli, especially in young adults having experienced an unexplained TIA without underlying cardiopathy. TEE is an easy-to-use and well tolerated technique for detecting the cardiac origin of emboli in unexplained stroke. Whether to opt for a medical or surgical treatment to avoid recurrences is discussed. PMID- 1605462 TI - Bone manifestations associated with acquired immunodeficiency syndrome (AIDS). AB - To date, descriptions of bone manifestations associated with the acquired immunodeficiency syndrome (AIDS) have mostly been limited to case reports. Six such cases observed in our Departments of Rheumatology and Infectious Diseases, are reported. Three types of manifestations were observed: malignant lymphoma, infectious osteomyelitis, and reflex sympathetic dystrophy syndrome (algoneurodystrophy) secondary to central nervous system involvement. PMID- 1605463 TI - [Hashimoto's disease and hyperthyroidism]. PMID- 1605464 TI - [Severe meningoencephalitis in acute Coxiella burnetii infection]. PMID- 1605465 TI - [Association of progressive multifocal leukoencephalitis and sarcoidosis]. PMID- 1605466 TI - [Hemorrhagic rectocolitis and viral pericarditis]. PMID- 1605467 TI - Neurohumoral modulation of functional reserves and activity of host defenses. PMID- 1605468 TI - Glucocorticoids activate a suicide program in mature T lymphocytes: protective action of interleukin-2. AB - Viability of T cell blasts obtained by concanavalin A stimulation of mouse spleen cells markedly decreases when these cells are exposed to glucocorticoid hormones in the absence of interleukin-2. The mechanism underlying the lysis of the mature lymphocytes seems to correspond to the apoptotic type of cell death inasmuch as an early degradation of DNA into oligonucleosome-length fragments is observed. Moreover, glucocorticoid-induced DNA fragmentation is delayed in the presence of an inhibitor of protein synthesis. Induction of the cell death program by glucocorticoids is most likely mediated through the interaction with a specific glucocorticoid receptor as suggested by the structure-activity relationship of the various steroids tested. Interestingly, the presence of a saturating dose of IL-2 during the treatment of concanavalin A blasts with glucocorticoids totally abolished DNA fragmentation and cell lysis. PMID- 1605470 TI - Naloxone and anaphylactic shock in the rat. PMID- 1605469 TI - Opioid modulation of immunoglobulin production by lymphocytes isolated from Peyer's patches and spleen. PMID- 1605471 TI - Occurrence of vasoactive intestinal peptide (VIP) in lymphoid organs from rat and mouse. PMID- 1605472 TI - Interaction of Leu-enkephalin and alpha-interferon in modulation of NK-activity of human peripheral blood lymphocytes. PMID- 1605473 TI - Immunoreactive growth hormone production by cultured lymphocytes. PMID- 1605474 TI - Macrophages and astroglial interactions in repair to brain injury. AB - The response to brain injury appears to involve a well-coordinated interaction between microglia, extrinsic macrophages and glial cells. The proliferation of glial cells at the site of the injury appears necessary to reseal the brain. Most data support the view that glial cell (and fibroblast and endothelial cell) proliferation is driven by IL-1-like factors liberated by the invaded macrophages. Although less well established, most data, including our own suggest that glial cells contribute to the neutrotrophic response found after brain injury. In vitro evidence suggests that glial cell-mediated production of neurotrophic factors may also depend, like glial cell proliferation, on actions of interleukins (e.g., IL-1) at the site of the injury. Moreover, evidence of in vivo experiments, showing that immunosuppressants inhibit the glial response and that inhibition of glial proliferation suppresses the neurotrophic response are in line with this view. Restoration of the damaged brain site may also be compatible with the lack of T and B cell infiltration at the lesioned site. Factors such as prostaglandins and TGF-beta released from glial cells may be involved in controlling and counteracting a threatening immune attack. In conclusion, tissue repair in the brain appears to be centered around regulatory properties of glial cell proliferation, enhancement of neuronal growth and inhibition of a local immune response. PMID- 1605475 TI - Suppression of adjuvant-induced disease (AID) by a novel analgesic-opioid agonist which also possesses antioxidant activity (neuroimmunomodulation). AB - A centrally acting analgesic-opioid agonist, PM, suppresses the primary inflammation and the secondary lesions of adjuvant-induced disease in rats. This compound also possesses antioxidant properties and inhibits the carrageenin induced edema in mice. PM, therefore, is interfering to immune functions probably by binding to opioid receptors on lymphocytes and to inflammatory cells by its antioxidant activity. PMID- 1605476 TI - Possible role of interferon-gamma in ovarian function. PMID- 1605477 TI - Tumor necrosis factor alpha and interleukin-1 alpha increase pain thresholds in the rat. PMID- 1605478 TI - Muramyl peptides as paradigms in neuroimmunomodulation. PMID- 1605479 TI - Spiperone binding in lymphocytes: part of a dopamine uptake system? PMID- 1605480 TI - Altered cerebral dominance in atopy and in children of asthmatic mothers. PMID- 1605481 TI - Psychoemotional, cognitive, chronoendocrine, and immune responses to a survival performance in an African desert. Evidence for divergent effects. PMID- 1605482 TI - The effects of handling adult mice on immunologically relevant processes. PMID- 1605483 TI - Mechanisms of the behavioral effects of interleukin 1. Role of prostaglandins and CRF. AB - Sickness behavior induced by IL-1 can be assessed quantitatively by measuring disruption of schedule-controlled behavior and loss of interest in social activities displayed by rats or mice injected peripherally or centrally with this monokine. These effects are mediated via the release of prostaglandins since they are blocked by the prostaglandin synthesis inhibitors indomethacin and piroxicam. They do not depend, however, on the central release of CRF, since they are not altered by central administration of either CRF or the specific antagonist of CRF receptors. PMID- 1605484 TI - Psychosocial factors and immune senescence in the aged primate. AB - With increasing age, old animals and humans show decreases in a number of immune responses indicative of the process of immune senescence. Our studies investigated whether social companionship, as a potentially positive psychological intervention, would increase lymphocyte proliferation and natural killer cell activity in the aged nonhuman primate. Contrary to our initial hypothesis, social stimulation resulted in decreased immune responses in old monkeys. With specific modifications of the housing conditions it was possible to prevent these decreases in immune responses from occurring, but social companionship still failed to enhance immune responses in the aged monkey. PMID- 1605485 TI - Disturbances in the circadian rhythm of T cell subsets in stressed mice. PMID- 1605486 TI - Evaluation of stress effects in an experimental autoimmune disease. PMID- 1605487 TI - Metastasis and neuroendocrine system in stressed mice. PMID- 1605488 TI - Neurovascular immunology: a 25-year odyssey. AB - Small vasoactive neurotransmitter molecules with a long evolutionary history of involvement in biological defense and inflammation play important roles in the up regulation and down-regulation of the immune response and with similar effects on neuronal and lymphocyte transmembrane signaling molecules and mechanisms. The longest acting of these stimulatory molecules on lymphocyte traffic, substance P and bradykinin, also are transmitters of impulses relating to heat and pain. Heat and pain have been primordial stimuli to learning and memory--immunological as well as CNS. PMID- 1605489 TI - HLA class II antigens in endogenous psychoses. PMID- 1605490 TI - Immune changes induced by electroconvulsive therapy (ECT). AB - There is a significant increase in the percentage and absolute number of activated lymphocytes (OKT10+, IL2R1+) after ECT treatment of major depressive disorder. There is an acute decrease in the absolute number of total lymphocytes, T8+ and Leu11+ cells one hour after a single ECT. PMID- 1605491 TI - Growth hormone response to clonidine and cortisol secretion pattern predict changes in peripheral blood lymphocyte subsets in major depressive patients. PMID- 1605492 TI - Tumor necrosis factor-alpha and interferon-gamma synthesis by cerebrospinal fluid derived T cell clones in multiple sclerosis. AB - T cell clones derived from cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) were analysed for their capacity to produce interleukin 2 (IL-2), interleukin 4 (IL-4), interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). They were also compared with liver-infiltrating T cell clones from patients with chronic active hepatitis. All the CSF T clones (both CD4+ and CD8+) produced large amounts of IFN-gamma and particularly of TNF-alpha, that was synthesized in a significantly larger amount than compared clones. Moreover, they were capable of secreting IL-2, but not IL-4. From our results, we conclude that first, the CSF CD4+ T clones could constitute a subset with functional properties similar to the T helper 1 (Th1)/inflammatory cell subset of the mouse; and second, the large amounts of TNF produced by CSF T cell clones strongly suggests a significant role for this cytokine as well as of IFN-gamma in MS immunopathogenesis. PMID- 1605493 TI - Elevated interleukin 2 levels in serum and cerebrospinal fluid of patients with relapsing-remitting multiple sclerosis. PMID- 1605494 TI - Early socialization and development of cancer in later life. Biopsychosocial and psychoneuroimmunologic aspects. PMID- 1605495 TI - Central interferon alpha suppresses the cytotoxic activity of natural killer cells in the mouse spleen. PMID- 1605496 TI - Modulation of cutaneous immune reactions by centrally applied methionine enkephalin. PMID- 1605497 TI - The pineal-immuno-opioid network. Mechanisms and significance. PMID- 1605498 TI - Direct innervation of lymphatic organs in the rat. PMID- 1605499 TI - Electrophysiological correlation of neuroendocrine and immune responses in proestrous rat. PMID- 1605500 TI - Evidence for the conservation of an immunoreactive monokine network in invertebrates. AB - Mytilus edulis, a marine bivalve mollusc, contains hemocytes that share certain properties with cells of the human monocyte-macrophage lineage. Because of this and previously reported similar responses to opioids between Mytilus hemocytes and human granulocytes, we determined whether Mytilus might also possess monokines or an immune monokine-like network. We chose to study two monokines, interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF). We found that Mytilus hemocytes respond to recombinant human IL-1 and TNF in a fashion similar to human granulocytes. Furthermore, we show that as in the human system, it appears that IL-1 mediates at least part of its effects through immunoreactive (ir) TNF in Mytilus. Finally, we show that Mytilus hemolymph contains ir IL-1 and TNF. To our knowledge, this is the first demonstration of these substances in this system. PMID- 1605502 TI - Interdependence of growth hormone and thyroid hormone action on thymulin synthesis: clinical evidence. PMID- 1605501 TI - Peptidergic neurons and vasoactive intestinal peptide modulate experimental delayed-type hypersensitivity reactions. PMID- 1605503 TI - Zinc-dependent thymic hormone failure in AIDS. PMID- 1605504 TI - [Tinea faciei: epidemiology]. AB - Because of its clinical peculiarities responsible for many diagnostic errors resulting in potentially toxic treatments, tinea faciei should be regarded as a process with a personality of its own. The authors have reviewed 46 cases of tinea faciei, evaluating and highlighting their clinical and epidemiological peculiarities. As regards age and sex, two peaks of maximum incidence can be found: one in childhood, the other in adults older than forty. Many lesions progress over more than 12 months before they are diagnosed. Their peculiar clinical features suggests various initial diagnoses, the most frequent of which are related to photosensitivity (lupus erythematosus, polymorphous light eruption). Among the most frequently isolated dermatophytes, T. mentagrophytes var. granulosa and T. rubrum are outstanding. PMID- 1605505 TI - [Campaign of early detection of melanoma in the Provence-Alpes-Cote-d'Azur area 1989. Lessons of an experience]. AB - The prognosis of melanoma is closely related to tumor thickness at the time of surgical excision. Thickness depends on the duration of disease before diagnosis. This underlines the importance of information campaigns to promote early diagnosis of melanoma. The purpose of this study was to estimate the cost and effectiveness of a media campaign for the early screening of malignant melanoma (MM) at national level. This trial, the first of its kind in France, was conducted in the spring of 1989 in the Provence-Alpes-Cote d'Azur-Corse region. The campaign combined an effort to inform and heighten awareness in the medical community and the broadcast of an information movie for the general population on a regional TV channel. Following the campaign, the number of MM diagnosed in a representative selection of pathology laboratories increased significantly compared with the same period of the previous year: + 108 p. 100 over the 10 first weeks, + 47.6 p. 100 over 6 months. This increase was mostly for MM of low thickness (less than 1 mm) which have a good prognosis: + 74 p. 100 over 6 months. However MM distribution by thickness was not significantly different from one year to the next. Although the number of added cost generated by this campaign could not be precisely determined, these positive initial results argue for a national prevention campaign based on the lessons of this experience. PMID- 1605506 TI - [Congenital cutaneous Langerhans histiocytosis. Apropos of 7 cases]. AB - Seven cases of congenital Langerhans' cell histiocytosis (LH) are reported, with emphasis on clinical and immunohistochemical features. This is a polymorphic disease at birth. In 4/7 cases, the diffuse, generalized rash could be classified as cutaneous Letterer-Siwe disease (LSD); 3/4 remained purely cutaneous and healed in less than 3 months; whereas the fourth-one persisted, pulmonary lesions appeared, and the infant died on his 40th day. In 3/7 cases, the clinical diagnosis at birth was either a Blueberry Muffin Baby (BMB) or Hashimoto-Pritzker type LH (HPLH); the lesions healed rapidly, although one cas was contradictory: typical BMB at birth, histology mimicking a monoblastic cutaneous leukemia, no T.O.R.C.H. syndrome, normal bone marrow, immunophenotyping of LH, auto involution; 2/3 were MZ twins, both with few lesions. We would like to stress the fact that the clinical spectrum of LH should include BMB, which, however, in most cases must be considered a differential diagnosis. Regarding cutaneous congenital LH, an eponymic classification (LSD, HPLH) is difficult to follow strictly, because overlapping pictures are observed. There is a wide spectrum of cutaneous congenital LH. The main problem at birth is the lack of prognostic criteria. Neither the presence of the rash at birth, nor its type and extension, is necessarily evidence of risk of systemic disease. Cases of HPLH involute, as also do cases of cutaneous LSD, and the "Blueberry Muffin" type of LH; overlapping clinical aspects exist. Histopathological data, electron microscopy or immunohistochemistry, define LH, but they do not enable the outcome to be predicted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605507 TI - [Unilateral blepharochalasis]. PMID- 1605508 TI - [Blepharochalasis or Fuchs syndrome in young subjects. 2 cases]. PMID- 1605509 TI - [Foreign body granuloma on calcified loa loa filariasis]. PMID- 1605510 TI - [Ostial eccrine porokeratosis and dermal duct nevus]. PMID- 1605511 TI - [O'Brien's actinic granuloma]. PMID- 1605512 TI - [Verruciformis epidermodysplasia in a black woman with hyperpigmented macula of the palms]. PMID- 1605513 TI - [Peristomal gangrenosum pyoderma]. PMID- 1605514 TI - [Acquired hypertrichosis of eyelashes in AIDS]. PMID- 1605515 TI - [Reed's nevus]. PMID- 1605516 TI - [A case for diagnosis: superficial pemphigus presenting as giant keratotic lesions]. PMID- 1605517 TI - [A case for diagnosis: isolated sarcoidosis of the scalp presenting as cicatricial alopecia]. PMID- 1605519 TI - [Epidemiology of dermatophytosis]. PMID- 1605518 TI - [Cutaneous calcinosis]. PMID- 1605520 TI - [Value of therapeutic circumcision in diffuse condylomata acuminata]. AB - Therapeutical circumcision (posthectomy) in nine patients presenting with diffuse penile warts. CO2 laser circumcision resulted in a 100 p. 100 cure rate after a 3 month follow-up in patients with diffuse warts of recent onset, and a 75 p. 100 cure rate in patients with recalcitrant warts. PMID- 1605521 TI - [Paederus dermatitis: apropos of an outbreak in Conakry (Guinea) in November 1989]. AB - Paederus sabaeus is a coleopter of the Staphylinidae family. With its toxins present in the hemolymph (pederin, pseudopederin, pederone), it causes a delayed vesicular inflammatory dermatosis. The contact between skin and toxin is only possible when the insect is injured or killed, which occurs most frequently when it is crushed on the skin. In November 1989, in Conakry, a huge proliferation of this insect was responsible for an epidemic of Paederus dermatitis. The European sailors working in the port of this town were affected preferentially, as well as the entire European population for sociocultural reasons. The clinical picture is very characteristic when the lesions are linear or "kissing lesions" on both sides of the folded part of an articular joint. This dermatosis is more frequent on the uncovered parts of the body. Healing is spontaneous, requiring 7 to 10 days, if there are no further infections. PMID- 1605522 TI - [Pseudoxanthoma elasticum. A X-ray microanalytic study]. AB - We present a very typical case of pseudo-xanthoma elasticum (PXE) with very remarkable cutaneous lesions, a great number of angioid streaks and, at the moment, with no involvement of the peripheral vascular system. From a genetic standpoint, we believe it must be considered as recessive Type I. An X-ray microanalysis was performed showing intense Ca and P deposits in the affected areas as well as complete absence of Si. PMID- 1605523 TI - [Pseudoxanthoma elasticum and perforating elastoma]. PMID- 1605524 TI - [Mycosis fungoides during B-cell lymphoma]. PMID- 1605525 TI - [Scleroderma-like syndrome with bullous morphea during treatment with 5 hydroxytryptophan, carbidopa and flunitrazepam]. PMID- 1605526 TI - [Candida albicans onychomadesis. Neonatal contamination]. PMID- 1605527 TI - [Horton's disease and myelodysplastic syndrome associated with unusual cutaneous manifestations]. PMID- 1605528 TI - [Association of psoriasis and atopic dermatitis. A prospective study]. PMID- 1605529 TI - [Recurrent oral aphthous ulcer, monoclonal gammapathy and chronic lymphoid leukemia]. PMID- 1605530 TI - [A case for diagnosis: Pseudomonas aeruginosa intertrigo]. PMID- 1605531 TI - [How and when a complement determination should be asked for in dermatology?]. PMID- 1605532 TI - [Diffuse bronchomalacia after double lung transplantation. Thoughts apropos of a case]. AB - A 40 year old woman suffered from respiratory insufficiency (arterial PaO2 = 47 mmHg) because of a chronic beryllium intoxication. On 6th June 1990, she underwent double lung transplantation with cardio-pulmonary bypass. Each lung was separately implanted via an extra-pericardial approach, and both bronchi were anastomosed at the hilum. On the seventh post operative day, a severe bilateral bronchial ischemia was noticed (black mucosa). Few weeks later, a diffuse bronchomalacia was noticed in the proximal and distal parts of both bronchial trees. To our knowledge, such a bronchial post-ischemic complication has never been reported. The explantation could be several added causes: imperfect preservation of the lung during harvesting, post operative pulmonary oedema, and operative use of an antifibrinolytic agent (aprotinin). PMID- 1605534 TI - [Interposition of a prosthetic graft between the ascending aorta and the abdominal aorta in the treatment of complicated or longstanding coarctations in adults]. AB - Although the direct approach to the aortic isthmus is unquestionable for an isolated coarctation of the thoracic aorta, recurrent coarctations of coarctation with associated cardiac lesions require a concomitant procedure, raise difficult surgical problems and expose to a high operative risk. Another technique consists of performing an ascending aorta-abdominal aorta by-pass, with a prosthetic tube. From 1977 to 1988, this technique was performed in 8 patients: 3 with recurrent coarctations, 4 with coarctation associated with a surgical aortic insufficiency (2 ascending aortic aneurysms with aortic insufficiency) and 1 with abdominal aorta coarctation. The mean age was 48.3 years (range from 31 to 72 years), the mean follow-up was 44.3 months (range from 4 months to 10 years 5 months). There was no mortality and no morbidity during the follow-up. The functional result is good, without high blood pressure and with no blood pressure difference between the arms and the legs. Postoperative angiographies showed that all the by-passed were patent. PMID- 1605533 TI - [Traumatic isthmic ruptures of the aorta during the acute phase. Reevaluation of surgical treatment. Thoughts apropos of 47 cases]. AB - From 1976 to 1989, 47 patients with traumatic aortic rupture in the area of the isthmus were seen in our institution; 4 patients died from exsanguination before definitive repair. Forty-three patients were operated on. Most of them (n: 41) underwent repair using partial bypass with pump oxygenator. There were 3 postoperative deaths. No patient developed postoperative paraplegia; 2 patients presented totally regressive spinal disturbances 5 and 8 days after surgery. Two of the 38 survivors were lost to follow-up. Postoperative angiography revealed an excellent aortic result in all cases especially in young patients, except two (1 stenosis, 1 aneurysm). Our experience and a review of the literature indicate some observations: despite rapid transport and evaluation, some patients died from exsanguination before definite repair. Cardiopulmonary bypass and correction of metabolic disturbances may decrease the probability of paraplegia and heparinisation did not increase the risk when orthopedic or abdominal lesions were treated before aortic lesion. Direct repair is recommended as the procedure of choice, especially in young patients, angiographic controls showed excellent results and long term follow-up is very satisfactory. PMID- 1605535 TI - [Resection of lung neoplasm in patients aged 70 years and over. Apropos of a series of 193 resections]. AB - Lung cancer in the elderly is an active cancer. Due to the poor tolerance of radiotherapy and chemotherapy, and the ever increasing life expectancy of patients over the age of 70 years, surgery remains the treatment of choice for these lesions. We report a series of 193 patients over the age of 70 years, the high postoperative mortality of 19% during the first month was counterbalanced by a 5-year survival of more than 20%. The criteria of operability must be rigorous and based on objective elements, especially lung function and the patient's good psychological state. PMID- 1605536 TI - [Lobectomies enlarged to the main bronchus in the conservative treatment of lung carcinoma. Apropos of 75 cases]. AB - From february 1965 to march 1990, 70 squamous cell carcinomas, 3 adenocarcinomas and 2 undifferentiated lung cancer were operated by lobectomy extended to the main bronchus: 44 right upper lobectomies, 22 left upper lobectomies, 5 left lower lobectomies, 2 right lower lobectomies, 1 middle lobectomy and one lower and middle bilobectomy. Respiratory function prevented pneumonectomy in 1 out of 3 patients. The postoperative mortality related to surgery (2.7%) has been eliminated since the introduction of systematic protection of the pulmonary artery from the bronchial suture (1976). The sutures are performed with very fine suture material. Endoscopic follow-up is essential: 11 cases of suture granuloma (1 laser) and 4 cases of fibrotic stenoses, including 1 post-irradiation stenosis (2 lasers). Fifty-three patients were N0 (28 T1, 22 T2, 3 T3) and 22 were T+ (including 4 N2). The actuarial survival for the N0 was 91% at 1 year and 60% at 5 years and decreased to 63% and 40% for N+. Eighty-three percent of the late cancer-related deaths had metastatic disease. Lobectomies extended to the main bronchus do not appear to compromise the oncological value of the resection and they offer the possibility of resection in some respiratory failure patients. PMID- 1605538 TI - [Cannonball pulmonary hamartochondroma. Apropos of a case--review of the literature]. AB - Chondroid hamartomas disseminated in both lung fields were discovered in a 76 year old man presenting with recurrent haemoptysis. In view of this metastatic cannonball appearance and the negative investigations, exploratory thoracotomy was performed, revealing the correct diagnosis. Although classical, this form of hamartoma is rare and warrants a case report. PMID- 1605537 TI - Surgery for congenital malformations of the lung. AB - In the course of a survey conducted in 59 hospitals performing thoracic surgery, 14 hospitals supplied data that could be used for the study. Out of 1347 anomalies diagnosed 1343 were surgically treated, with a 30-day mortality rate of 0.3% (5 patients). In a retrospective study over a period of 10 years (1978-1988) we identified 198 anomalies out of a total of 6350 thoracotomies; so our percentage grading of pulmonary anomalies is supported by the data of the above mentioned survey according to which cystic pulmonary malformations such as inhibition malformations, excess malformation and lobar emphysema represent a majority with 72.2% (survey 83%). Congenital anomalies of lung formation occurred in 23% of the patients of the survey and in 15% of our own patients. Therapy consisted of parenchyma-saving surgery, i.e. enucleation (n = 87), segmental resection (n = 65) and lobectomy (n = 63) with bronchoplastic reconstruction; there was no 30-day mortality. Adenomatoid-cystic malformation, lymphangiectasis, congenital lobar emphysema and stenosis of the tracheobronchial tree are often an indication for immediate surgical treatment in neonates. Solitary cysts, bronchiectasis, sequestration of the lung, an AV-fistula present with symptoms mostly between the ages of 20-40 and therefore were surgically treated secondarily. PMID- 1605539 TI - [Secondary bronchogenic pulmonary hydatidosis]. AB - Secondary bronchogenic hydatid disease is a rare and little known complication of primary hydatid cyst of the lung, which is even refuted by some authors. We report 7 cases of secondary bronchogenic hydatid after surgical cure of a hydatid cyst which had ruptured into the bronchi, while the last case concerned a young girl who was treated by corticosteroids for rheumatoid arthritis and who developed secondary bronchogenic hydatid from a cyst rupturing into the bronchi in the absence of surgery. Hydatid dissemination was ipsilateral to the primary cyst in 5 cases, controlateral in one case and bilateral in one case. Five patients underwent radical surgery. The patient with bilateral dissemination was operated on one side and a large number of residual cysts were eliminated by vomica, as for the last patient; these two patients are still under surveillance. The operation and general anaesthesia played a predisposing role in the pathogenesis of this complication and inhibition of immune mechanisms could also play a role. Prevention is necessary when treating a hydatid cyst of the lung which has ruptured into the bronchi. Treatment is surgical, bearing in mind that a large number of secondary cysts can be eliminated by vomica or may involute spontaneously. PMID- 1605540 TI - [Spontaneous and recurrent pneumothorax. Surgical treatment. Apropos of 278 cases]. AB - Over the past 19 years, 278 patients (238 men-40 women) have undergone 325 parietal pleurectomies: 311 transaxillary apical and 14 full pleurectomies. Mean age was 32 +/- 12 years. The overall male:female ratio was 6:1. Surgical treatment was performed for either recurrence of spontaneous pneumothorax or failure to respond adequately to management by tube drainage. Thirty-six patients underwent one stage bilateral apical pleurectomy. On the basis of our experience (idiopathic pneumothorax: 311; chronic obstructive lung disease: 12; histiocytosis X: 2), we advocate the use of transaxillary apical pleurectomy for the younger age group with recurrent idiopathic pneumothorax and a full pleurectomy in the older age group. Major complications occurred in 1.9% of cases (re-exploration for haemorrhage: 5 cases; for air leak: 1 case). The recurrence rate in this group of patients was 1% (3 in 278 patients: one of them has been reoperated). PMID- 1605541 TI - [Atypical pleural effusion secondary to transdiaphragmatic communication. Apropos of two cases: a chylothorax and a hydrothorax]. AB - We report two cases of pleural effusion in which a subdiaphragmatic cause was noted. In both cases it was necessary to obliterate a defect in the diaphragm via a thoracic incision. In one case, a left chylothorax occurred in a patient with hepatic cirrhosis. In this case, it was postulated that the normal lymphatic pathway through the right hemidiaphragm could have been stopped by pleural sequelae from right lobectomy. In the other case, a right pleural effusion occurred after peritoneal dialysis. It is a well known pathological entity: the structural defect can be observed by separation of collagen bundles in the tendinous diaphragm. This type of pleuro-peritoneal communication is well known in women suffering from menstrual pneumothorax or in patients treated by peritoneal dialysis. PMID- 1605542 TI - [Extrapancreatic hypoglycemic tumors. Apropos of a case of pleural fibrosarcoma]. AB - The authors report a case of pleural fibrosarcoma associated with severe hypoglycaemia. Chromatography of the patient's serum and tumour fragments revealed a substance with a high molecular weight and an insulin-like activity. Professor Poffengarger's laboratory identified this substance as Non Suppressible Insulin-Like Protein or NSILAp which induces insulin-like effects on various tissues. A review of the literature is presented in the light of this case. PMID- 1605543 TI - [Posterior mediastinal thymus. Apropos of a case in a child]. AB - Posterior and upper mediastinal localization of the thymus gland is uncommon in young children. Presenting symptoms and signs are very variable from incidental diagnosis to bronchopneumonial with atelectasias of the left upper Chest X-Ray and CT Scan are sufficient to make the diagnosis. Treatment of complicated forms with bronchial compression requires thoracotomy and surgical excision. PMID- 1605544 TI - [Tracheal neurofibroma and Recklinghausen's disease]. AB - Neurogenic tumours arising in the trachea are rare; the association with Von Recklinghausen's disease is exceptional. Only two cases of tracheal neurofibroma with neurofibromatosis have been reported. We report on another patient, a thirty year old man, who presented with acute shortness of breath; laser resection was performed via an endotracheal approach, then, a few days later, resection of the exotracheal tumor and tracheal segment was performed. Postoperatively, the patient did well for nine years without any respiratory complaint or neurofibromatosis relapse. PMID- 1605545 TI - [Esophageal perforations. Results of a national survey]. PMID- 1605546 TI - [Pericardioscopy: techniques, indications and results. Apropos of an experience with 70 cases]. AB - Pericardoscopy (PCS) is an original method of examination of the pericardial cavity. Its principle is derived from pleuroscopy and the apparatus is derived from mediastinoscopy. The main indication for this technique is the diagnosis of pericardial effusions. Sixty-five PCS were performed for this purpose, allowing an accurate etiological diagnosis in 35 cases. The etiological diagnosis was based on the clinical and paraclinical context in 4 other effusions, considered to be idiopathic after PCS. In 23 cases, the etiology remained uncertain, but a tuberculous or neoplastic etiology was ruled out after PCS. Three false negative results were obtained. Complete cleaning of the pericardial cavity allowed favorable immediate and mid a term outcome, avoiding possible constriction. Finally, PCS established the operability of two bronchial cancers, located in the hilar area and suspected of intrapericardial extension (PCS was performed in these cases in absence of pericardial effusion). PMID- 1605547 TI - [Ectatic tumoral thrombosis of the superior vena cava revealing thyroid cancer]. AB - Microscopic angio-invasion by carcinoma of the thyroid is known. Extension into the great veins is much more uncommon. Most of the cases which have been previously described were discovered on post-mortem examination. We report the case of a 55 year-old woman who was found to have an asymptomatic small cervical goiter 6 years ago; during the last 12 months she developed superior vena cave (SVC) syndrome radiological investigation (angiography, CT scan) and surgical exploration showed a carcinoma of the thyroid with intraluminal extension of the tumor leading to thrombosis and ectasia of the SVC. Surgery was performed with resection of the whole thyroid, the SVC and the innominate veins. A double prosthetic venous by pass was then inserted between the innominate veins and right atrium. Five years after resection, the patient has no recurrence or metastatis and no clinical symptom of SVC syndrome. To our knowledge, this is only the third reported case successfully treated by surgery. PMID- 1605548 TI - [Anatomical bases for bronchial arterial revascularization in double lung transplantation]. AB - A study of the bronchial arterial blood supply was conducted to facilitate in surgical attempts of bronchial revascularization in double lung transplantation. This study consisted of 20 cadaveric anatomical dissections of the bronchial arterial blood supply as well as a retrospective review of 50 bronchial arteriograms. The right bronchial tree was supplied by an artery originating from the right intercostal bronchial arterial trunk in 76 to 95% of the cases. This artery also supplied the distal trachea and the carina in over 80% of cases as well as the proximal left bronchial tree via a network of small collaterals found in the subcarinal compartment and adventitial tissues located on the anterior surface of the descending aorta. A common arterial trunk for both the right and left bronchial trees was found in 12 of the 20 dissections (60%). Left bronchial arteries were much smaller and less consistent. Proximity of the bronchial arteries orifices was frequently observed: in 10 of the 20 dissections it allowed simultaneous reperfusion of more than one vessel. To maintain the vascular anastomotic network in between the right and left trees, extensive vascular dissection and carinal resections are prohibited. This will allow revascularization of the whole tracheal bronchial tree via the supply of the origin of the RICBA. PMID- 1605549 TI - [Surgery by celioscopy and medical responsibility]. PMID- 1605550 TI - [Place of surgery in primary digestive non-Hodgkin's lymphomas]. PMID- 1605551 TI - [3606 cholecystectomies under celioscopy. The Register of the French Society of Digestive Surgery]. AB - Early results of laparoscopic cholecystectomy must be evaluated. In this way, the "Societe Francaise de Chirurgie Digestive" started to collect records of laparoscopic cholecystectomies from December 1989. 119 surgeons from 67 departments of surgery have been included in this study. By February 1992, 3,606 procedures were collected. The mean age of these patients was 51 years. Sex ratio was 0.29. 21.5% of patients had a history of acute cholecystitis. An operative cholangiogram was performed in 6.4% of cases. The mean operating time was 80 minutes. An immediate laparotomy was required in 7.1% of cases including 12 common bile duct injuries. Postoperative complications were detected in 4.3% of patients. Among these, 51 patients needed a second operative procedure including 13 common bile duct injuries. Two patients died in the postoperative period (mortality: 0.056%). The mean hospital stay was 4.8 days. History of acute cholecystitis increased significantly the immediate laparotomy required (p less than 0.01) and the incidence of postoperative complications (p less than 0.01). The mortality of laparoscopic cholecystectomy seems to be equivalent to that of open cholecystectomy. On the other hand, the incidence of common bile duct injury seems to be increased. However, the absence of controlled study prevents us from comparing the results with the open cholecystectomy. Furthermore, the incomplete nature of this register prevents us from concluding whether it reflects the real dangers of laparoscopic cholecystectomy. A more rigorous evaluating method should be considered in the future. PMID- 1605553 TI - [Our experience of surgery for common bile duct lithiasis. Apropos of 370 cases]. AB - We report a series of 370 common bile duct stones in which the diagnosis was made preoperatively in 56% of cases. We performed: choledochotomy with Kehr drainage in 70% of cases, biblio-intestinal anastomosis in 20%, transcystic extraction with drainage via the same route in 7%, surgical sphincterotomy in 2%. The global mortality was 2.7% related to preexisting deficiency states. The residual stone rate was 5.6%. PMID- 1605552 TI - [Primary intrahepatic lithiasis]. AB - Isolated intrahepatic lithiasis is a very rare condition in western countries; the reported case has to be added to the 29 cases described to date in the literature. The pathogenesis of this disease is unknown; physical and chemical bile alterations favouring lithogenesis is the most reliable hypothesis. In this case the Roux-en-Y hepaticojejunostomy with cutaneous stoma allowed us to perform periodic cleaning of intrahepatic bile ducts until complete elimination of all stones. PMID- 1605554 TI - [Sixty-one cases of acute obstructions of the colon caused by cancer. Indications for emergency surgery]. AB - Sixty-one cases of acute malignant colonic obstruction were operated upon within 24 hours after the patient's admission, between 1979 and 1989: 10 for a right colon carcinoma, 51 for a left-sided lesion. Indications, for emergency operation were: complete clinical obstruction, iliac tenderness, radiologic ileal fluid levels and arrest on barium enema. The initial procedures consisted of 8 right hemicolectomies, and for the left-sided obstructions, 32 colostomies, 7 colectomies with immediate anastomosis, and 12 colectomies without anastomosis. Overall mortality was nil for the right side and 4% left-sided obstructions. The current surgical procedures of choice according to the authors are: right hemicolectomy for right-sided obstruction; elective colostomy for the left side. In case of doubt about the mechanism of obstruction or vitality of the colon, a midline approach for operative exploration, followed by colectomy without anastomosis is recommended. Colectomy with immediate anastomosis is possible in rare favourable cases. Subtotal colectomy is indicated in cases of ischemic lesions, caecal perforation or other colonic tumours. Intraoperative irrigation of the colon is rarely permitted in this particular variety of acute obstruction. PMID- 1605555 TI - [Four cases of tracheoesophageal fistulas in adults in intensive care units]. AB - Four cases of tracheo-oesophageal fistulae following mechanical ventilation are reported. The determining factors, revealing signs, and palliative and curative treatment are discussed based on a review of the literature. In this series, the tracheotomy cannula provided good protection of the upper airways in three cases of upper fistulae. In the other case, the fistula was too close to the carena, requiring the use of high frequency jet ventilation. The management of low, large fistulae is more problematic concerning the choice of technique and timing of the operation. PMID- 1605556 TI - [Elastofibroma dorsi. Apropos of 5 cases]. AB - Elastofibroma is a rare tumor mainly found under the scapula. Based on a recent study of five cases, we would like to stress the importance of making the diagnosis of elastofibroma, as this lesion simply consists of dysplasia of the elastic fibres and is not malignant as could be suggested by clinical examination. PMID- 1605557 TI - [Subcardial stomach diverticulum and gastroesophageal reflux]. AB - Gastric diverticulum is a rare disease, often benign and specifically located in the right paracardial region. The authors report a case of left paracardial diverticulum with gastro-oesophageal reflux. This association should be treated surgically with resection of the diverticulum, after failure of medical treatment. PMID- 1605558 TI - [Disorders of relaxation of the lower esophageal sphincter after resection of mediothoracic esophageal pulsion diverticulum]. AB - A pulsion diverticulum of the mid-thoracic oesophagus was resected because of severe dysphagia. A subdiverticular myotomy was associated for the treatment of non-propagated oesophageal contractions, without oesophageal low-sphincter abnormalities. Three months post-operatively, the dysphagia was still present and manometry showed the absence of lower sphincter relaxation after 45 percent of deglutitions; a lower oesophageal sphincter myotomy was performed, resulting in correction of the dysphagia and of the sphincter relaxation abnormalities. The deficit of the inhibitory nervous mechanism, responsible for abnormalities of lower oesophageal sphincter relaxation, was present in the entire intramural oesophageal plexus, but, was not symptomatic at the level of the IOS prior to resection of the diverticulum. PMID- 1605559 TI - [Stomach leiomyoblastoma: contribution of cytology. Apropos of a case]. AB - The authors report the case of a 51-year-old man with gastric leiomyoblastoma, presenting with a history of gastrointestinal bleeding and hemoperitoneum. CAT scan showed a mass measuring 10 x 10 cm arising from the stomach. At laparotomy the mass extended into the gastrosplenic omentum. A splenopancreatectomy was performed and the mass was excised for biopsy. The cytologic findings suggested a mesenchymal tumor; histology demonstrated the diagnosis of leiomyoblastoma. The postoperative course was uneventful. In the literature there is no evidence that intraperitoneal bledding from these tumors worsens survival. The cytopathologic features of leiomyoblastoma are discussed. PMID- 1605560 TI - [Pyloric exclusion for disinsertion of the papilla following closed trauma of the abdomen. Apropos of 2 cases]. AB - Two cases of disinsertion of the papilla following closed trauma to the abdomen were treated by suction of the papilla by a Y loop associated with temporary pyloric exclusion, gastroenterostomy and a feeding jejunostomy. The postoperative course was uneventful in the two patients. This technique is therefore indicated for associated pancreatic lesions which do not require cephalic duodenopancreatectomy. PMID- 1605561 TI - [Hydrothorax of hepatic origin. Description of a clinical case, pathophysiology]. AB - We admitted a 60 year old patient with severe right hydrothorax. He was known to suffer from decompensated non-alcoholic cirrhosis. His invaliding dyspnea was only temporarily improved by repeated thoracocentesis, due to the very rapid refilling of the thorax from the ascites; until the development of a "tension hydrothorax" with dangerous mediastinal deviation. By insertion a peritoneo venous shunt described by LeVeen the clinical picture was improved, and the patient no longe required further pleural aspiration. Six per cent of cases of ascites complicating hepatic cirrhosis may be associated with hydrothorax of the same origin. The diaphragm is normally perforated by a multitude of tiny virtual holes, closed by the peritoneum and the thoracic pleura. The high intra-abdominal pressure in ascites tears these fragile membranes, and allows the peritoneal fluid to overflow into the pleural cavity. Usually treated by fluid restriction and diuretics, when this condition becomes intractable or when a tension hydrothorax appears, interfering with respiratory function a LeVeen peritoneo venous shunt should be inserted. PMID- 1605562 TI - [Fibroma of the tunica albuginea. Apropos of a case]. AB - Fibroma of the tunica albuginea is a rare, benign lesion. Only twenty cases have been published. We have observed one case a solitary testis of a 40 years old patient. The treatment performed was enucleation. The interest of this case consists in the rarity of the case and the operative solution proposed. After a review of the literature, we summarise the characteristics of this disease. PMID- 1605563 TI - [Use of extracorporeal circulation oxygenators (CEC) in the European Economic Community (EEC)]. AB - This study analyses the growth of CPB in the EEC. The study situates its position in the world taking into account several indexes such as the Gross National Product and its growth the life expectancy and other technical or economic factors. Only a broad analysis could be performed for Europe to the irregular development of CPB. A more detailed analysis was performed for France thanks to a greater number of data. In this type of study the most important problem is to estimate the relevance and consistency of the data provided either by companies or by other organizations because they can change very quickly. PMID- 1605564 TI - Antagonists of nucleic acid derivatives as medicinal agents. PMID- 1605565 TI - Toxicology of hydrogen sulfide. AB - Significant progress has been made in determining the action of sulfide on the primary target organs. It is reasonably clear that sulfide causes both K(+) channel-mediated hyperpolarization of neurons and potentiation of other inhibitory mechanisms. It is not clear whether these processes are similar to those that occur in anoxia. Changes in perinatal and adult brain neurotransmitter content and release may be related to clinical impairment of cognition. H2S exposures at concentrations below the current occupational limits cause physiological changes in pulmonary function, thus suggesting that asthmatics are at risk. Studies of fetal and neonatal brain tissue have shown an abnormal development, and the long-term consequences of these neuronal changes have not yet been assessed. Finally, new approaches to therapy are required, such as the use of agents that actively remove sulfide from its sites of action. This may prove more useful in preventing some of the long-term adverse sequelae than the use of nitrites and hyperbaric O2, although the latter should be used in cases of pulmonary edema. PMID- 1605567 TI - Population pharmacokinetics/dynamics. PMID- 1605566 TI - Pharmacology of nonpeptide angiotensin II receptor antagonists. PMID- 1605568 TI - Glucuronidation and its role in regulation of biological activity of drugs. PMID- 1605569 TI - Geriatric pharmacology: basic and clinical considerations. PMID- 1605570 TI - Theoretical basis for a pharmacology of nerve growth factor biosynthesis. PMID- 1605571 TI - Therapeutic applications of oligonucleotides. PMID- 1605572 TI - Pharmacology of protein kinase inhibitors. PMID- 1605573 TI - Pharmacodynamic modeling of anesthetic EEG drug effects. PMID- 1605574 TI - Calcium-mediated mechanisms in chemically induced cell death. PMID- 1605575 TI - Role of covalent and noncovalent interactions in cell toxicity: effects on proteins. PMID- 1605576 TI - Concepts in chronopharmacology. AB - Circadian and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical and chemical agents including medications and foods are rather common phenomena. Time-related differences in drug effects depend upon endogenous circadian rhythms, which include metabolic pathways. In addition, chronopharmacology investigates drug effects on parameters (e.g. circadian period, peak time, amplitude, and adjusted mean) used to characterize biological rhythms. A better understanding of periodic and thus predictable changes in drug effects can be attained by consideration of complementary concepts: (a) The chronokinetics for a drug, i.e. dosing time dependent and predictable (rhythmic) changes in parameters used to characterize the pharmacokinetics (or the bioavailability) of a drug, e.g. Cmax, tmax, AUC, and t1/2; (b) the chronesthesy, i.e. rhythmic changes in susceptibility of the target biosystem to this drug, including CR in pharmacodynamic processes; and (c) the chronergy, i.e. the drug-integrated overall effect. One of the aims of chronopharmacology refers to the use of a chronopharmacological approach to clinical treatment so as to enhance both effectiveness and tolerance of a drug by determining the best biological time for its administration. PMID- 1605577 TI - The chemistry and pharmacology of avermectins. PMID- 1605578 TI - Tandem mass spectrometry: the competitive edge for pharmacology. PMID- 1605579 TI - Cytotoxic conjugates containing translational inhibitory proteins. PMID- 1605580 TI - Determinants of metabolite disposition. PMID- 1605581 TI - Inhaled toxicants and airway hyperresponsiveness. PMID- 1605582 TI - Catalytic sites of hemoprotein peroxidases. AB - The structures of the active sites of horseradish and cytochrome c peroxidase, prototypical peroxidases with an imidazole heme ligand, suggest that small substrates are generally oxidized by peroxidases at the delta-meso edge of the heme group. This inference is supported by experimental results on the Coprinus macrorhizus peroxidase (52), manganese peroxidase (51), lignin peroxidase (50) and, less definitively, lactoperoxidase (90). Macromolecular substrates, exemplified by the cytochrome c peroxidase-cytochrome c interaction, are likely to be oxidized at peroxidase surface sites bearing no specific relationship to the delta-meso heme edge. The second oxidation equivalent in the two-electron Compound I states of the peroxidases is stored either as a porphyrin radical or as a protein radical, although some peroxidases have both types of compound I. The factors that control the location of the second oxidation equivalent remain unclear. Classical peroxidases do not generally catalyze olefin epoxidation and other monooxygenations but do catalyze sulfoxidation reactions. This is best rationalized by physical separation of the substrate from the ferryl oxygen, possibly by a protein barrier, because results with cytochrome c peroxidase show that there is no inherent mechanistic reason for the inability of peroxidases to epoxidize olefins. It is not yet clear why the barrier to oxygen transfer reactions is circumvented during sulfur oxidation reactions, although one possibility is that the relatively stable sulfur cation radical that is initially formed disrupts the barrier. Chloroperoxidase, the principal nonclassical hemoprotein peroxidase so far examined, has an open active site that readily catalyzes P450-like monooxygenation reactions. The active site of chloroperoxidase is a potentially useful model for that of myeloperoxidase, but caution must be used in extrapolating from one to the other because myeloperoxidase has a histidine rather than thiolate fifth heme ligand and therefore is a classical rather than nonclassical peroxidase. PMID- 1605583 TI - Review of revues. PMID- 1605584 TI - (Mis)conceptions and reconceptions about traditional science. AB - "Traditional" science (ie, scientific work that has evolved from the natural sciences) is still said to rely on theory-neutral facts, quantitative data, and the search for universal laws. This depiction of science is incongruent with much contemporary thinking. This article examines three shifts in recent philosophy that are relevant for nursing science philosophy: the move from foundationalism to an understanding of the fallibility of science, the shift in emphasis from verification to justification of knowledge claims, and the recent examination of explanation by scientific realists. It is suggested that scientific realism may be a fruitful area of inquiry for philosophers of nursing science. PMID- 1605585 TI - Testing of nursing theory: critique and philosophical expansion. AB - The authors first critique Silva's 1986 article in Advances in Nursing Science entitled "Research Testing Nursing Theory: State of the Art." They specifically focus on her evaluation criteria for the empirical testing of nursing theory and then develop evaluation criteria for three alternative approaches to theory testing in nursing. In addition, they describe how philosophy in general, and epistemology in particular, affect testing of nursing theory. Finally, they raise philosophical issues and state conclusions related to the testing of nursing theory within the discipline and practice of nursing. PMID- 1605586 TI - Power and knowledge in nursing: a feminist poststructuralist view. AB - This article explores the concepts of power and knowledge from two philosophical perspectives, the feminist and the poststructuralist, and examines their application to nursing knowledge and nursing science. Principles of poststructuralist and feminist philosophies are presented. The role of the nursing-medicine power relation in the development of nursing knowledge and the interaction of gender issues in that relation are reviewed in the context of nursing history. Both past and current mechanisms that contribute to the maintenance of the nursing-medicine power relation are discussed. PMID- 1605588 TI - From preventive health behavior to health promotion: advancing a positive construct of health. AB - A concept analysis of preventive health behavior provided the foundation for this review of current health promotion research in nursing. Studies selected for review described or explained behavior for health promotion, illness prevention, or preventive health behavior. The major focus of this critical review is on the conceptualization and measurement of health promotion behaviors being investigated. Despite nursing's claim to an holistic idea of health, the biomedical model continues to influence indicators of health behavior and the context for promotion of healthy life styles. Major issues for future health promotion research relate to the lack of attention to theoretical definitions and multidimensional aspects of health behavior, and the triad of national strategies for health promotion are discussed. PMID- 1605587 TI - Cardiovascular disease in women and noncontraceptive use of hormones: a feminist analysis. AB - Cardiovascular disease (CVD) in women is being defined by biomedical researchers and physicians as part of the menopausal syndrome. Postmenopausal lowered levels of estrogen are presented as a prime cause of changes in cholesterol levels that are a risk factor for CVD. The biomedical model and hormone debate are described and analyzed, followed by a feminist perspective of CVD. This includes new federal policies that support CVD research. Nurses are encouraged to present a broader picture of CVD and its risks than that presented by the biomedical model and to empower women's understanding of this complex health issue through educational, clinical, and research endeavors. PMID- 1605589 TI - Application of Cox's interaction model of client health behavior in a weight control program for military personnel: a preintervention baseline. AB - This study represents a limited application of Cox's Interaction Model of Client Health Behavior in a weight control program for enlisted US Army soldiers. Relationships of client singularity variables (demographic characteristics, motivation, psychological distress, and designation as overweight or normal weight) to one another and to preintervention measures of client outcomes (health status, health risk) were examined in a sample of 154 soldiers. Hypotheses deduced from the model were tested using multiple regression. The Cox model received partial support, in that some client singularity variables were interrelated; they explained nearly half of the variance in health status, but less than 25% of the variance in health risk. Demographic characteristics were not effective predictors in the present study, perhaps because of the homogeneous sample. The model has potential utility for providing baseline information for preventive health programs in occupational settings. PMID- 1605590 TI - Influence of phospholipid/amphotericin B ratio and phospholipid type on in vitro renal cell toxicities and fungicidal activities of lipid-associated amphotericin B formulations. AB - We studied the influence of the lipid/amphotericin B (AMB) ratio and the phospholipid type on the in vitro renal cell toxicity and antifungal efficacy of lipid-associated AMB (L-AMB). L-AMB was prepared at one of two different lipid/AMB ratios (1 and 40) by incubating AMB with empty small unilamellar vesicles, made from one of three different phospholipids: dipalmitoyl-, dimirystoyl-, and distearoylphosphatidylcholine (DPPC, DMPC, and DSPC, respectively). Renal cell toxicity, investigated through an assessment of the Na dependent uptake of phosphate by proximal tubular cells, and fungicidal effect against Candida albicans were studied after 1 h of treatment at 37 degrees C. The amount of unbound AMB present in each L-AMB formulation was studied by use of circular dichroism. At a lipid/AMB ratio of 40, the three lipidic formulations were not toxic for renal cells but were less effective against C. albicans than AMB; however, DSPC-AMB, which contained 50% unbound AMB, was more effective against C. albicans than DPCC-AMB or DMPC-AMB, containing 0 and 13% unbound AMB, respectively. At a lipid/AMB ratio of 1, the antifungal effects of L-AMB and AMB were similar, whatever the phospholipid used, but only DMPC-AMB remained highly protective against AMB renal cell toxicity, despite the presence of the same amount of unbound AMB (50%) in DMPC-AMB and DPPC-AMB. We conclude that the in vitro activities and renal cell toxicities of different L-AMB formulations are influenced by the phospholipid type and the lipid/AMB ratio. The optimal ratio depends on the phospholipid itself. At a lipid/AMB ratio of 40, the antifungal activity depends mainly on the amount of unbound AMB in the formulation. At a lipid/AMB ratio of 1, the renal cell toxicity also depends on the fluidity of the phospholipid. PMID- 1605591 TI - Simple assay to screen for inhibitors of interaction between the human immunodeficiency virus envelope glycoprotein and its cellular receptor, CD4. AB - The binding of the human immunodeficiency virus envelope glycoprotein gp120 to the CD4 molecule is the initial step in the viral replicative cycle. This interaction is therefore an important target for therapeutic intervention for the treatment of human immunodeficiency virus infection. We designed an enzyme-linked immunosorbent assay which detects the interaction between recombinant soluble forms of CD4 and gp160. This assay could be used as an initial screen of libraries of synthetic chemical compounds and natural products. PMID- 1605592 TI - In vitro antibiotic susceptibilities of Neisseria gonorrhoeae isolates in the Philippines. AB - Antibiotic susceptibility surveillance testing was performed on clinical isolates of Neisseria gonorrhoeae collected in September 1989 in the Philippines. beta Lactamase was produced by 77 (55%) of 140 isolates. In vitro MIC testing revealed significant resistance to penicillin (MIC for 90% of isolates [MIC90], greater than 64 micrograms/ml), tetracycline (MIC90, 4 micrograms/ml), and cefmetazole (MIC90, 8 micrograms/ml). Spectinomycin resistance was rare (10 of 117), but the MIC90 was 32 micrograms/ml. Isolates were susceptible to fluoroquinolones and cephalosporins at the time of this survey, as evidenced by the MIC90s of ciprofloxacin (0.25 microgram/ml), norfloxacin (2.0 micrograms/ml), ofloxacin (0.625 microgram/ml), cefpodoxime (2.0 micrograms/ml), cefotaxime (1.0 microgram/ml), ceftazidime (0.25 microgram/ml), ceftizoxime (0.25 microgram/ml), and ceftriaxone (0.06 microgram/ml). To date, ceftriaxone resistance has not emerged, despite the widespread use of this antibiotic in the Philippines. PMID- 1605593 TI - Double-blind study comparing erythromycin and mupirocin for treatment of impetigo in children: implications of a high prevalence of erythromycin-resistant Staphylococcus aureus strains. AB - Staphylococcus aureus has been consistently isolated from a high proportion of impetiginous lesions, and in several recent studies, it was present in the majority of the cases. Since recently a large proportion of S. aureus strains in our community showed erythromycin resistance, we undertook a prospective double blind controlled study comparing topical mupirocin with oral erythromycin to determine (i) the prevalence of erythromycin-resistant S. aureus strains in impetigo and (ii) whether an increased rate of failure of erythromycin treatment was associated with such resistance. A total of 102 patients 3 to 185 months old (median = 49 months) were enrolled. Culture was positive for 97 of 102 (95%) patients, and S. aureus was present in 93% of the patients for whom cultures were positive. S. aureus was the single pathogen in 64% of these patients. Erythromycin-resistant S. aureus strains were present in 27 of 91 (28%) patients for whom cultures were positive. In all cases but one, S. aureus was resistant to penicillin, and in all cases it was sensitive to mupirocin. A marked difference was observed in favor of mupirocin in the clinical courses of the disease. However, only patients with erythromycin-resistant S. aureus strains had unfavorable courses compared with those treated with mupirocin (failure rate, 47 versus 2%, respectively). Patients with erythromycin-susceptible S. aureus strains who received erythromycin had a failure rate of 8%. In four patients, S. aureus strains initially susceptible to erythromycin became resistant during treatment. We conclude that erythromycin-resistant S. aureus strains are commonly isolated from impetigo in our region.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605594 TI - A model of cefoperazone tissue penetration: diffusion coefficient and protein binding. AB - The apparent diffusion coefficient of a bound drug, cefoperazone, was studied. The protein binding of cefoperazone was studied by voltammetry, a technique which permitted instant measurements. The apparent diffusion coefficients were similar in agar and fibrin and lower in rat brain tissue. The influence of protein on the value of the apparent diffusion coefficient was negligible. The hypothesis that only the free drug diffuses was supported. The percentage of binding determined by voltammetry corresponded to the true concentration of drug which diffuses and is much lower than the percentage of binding determined by the ultrafiltration centrifugation method. This discrepancy could be explained by the rate of dissociation of the protein-drug complex. PMID- 1605595 TI - Relationship of pharmacokinetics and drug distribution in tissue to increased safety of amphotericin B colloidal dispersion in dogs. AB - The safety, pharmacokinetics, and distribution in tissue of an amphotericin B (AmB)-cholesteryl sulfate colloidal dispersion (ABCD) were compared with those of micellar amphotericin B-deoxycholate (m-AmB). Dogs received 14 daily injections of ABCD (0.6 to 10 mg/kg of body weight per day) or m-AmB (0.6 mg/kg/day). Safety was evaluated by monitoring body weight, hematology, clinical chemistry, and urinalysis during the study and by microscopic examination of tissues at the time of necropsy (day 16). AmB concentrations in plasma were measured in some groups on days 1, 7, and 14 and in necropsy tissue samples. ABCD produced a spectrum of toxic effects in the kidneys, gut, and liver similar to those of m-AmB, but ABCD was eightfold safer than m-AmB. The highest tolerated dose of ABCD (5.0 mg/kg/day) produced effects similar to those of m-AmB (0.6 mg/kg/day). ABCD produced lower concentrations in plasma than an equal dose of m-AmB did. Clearances on days 7 and 14 were higher for ABCD (304 and 295 ml/h.kg) than they were for m-AmB (67 and 53 ml/h.kg). Concentrations in plasma reached steady state after ABCD administration, but they increased after repeated dosing with m-AmB. Diurnal fluctuations in AmB concentrations in plasma were observed 4 to 8 h after the time of dosing. ABCD resulted in lower AmB concentrations in tissue than m AmB did, except in the reticuloendothelial system. Up to 90% of AmB administered as ABCD was recovered from the liver and spleen on day 16. Reduced drug levels in the kidneys and gut correlated with reduced indications of toxicity in these organs after ABCD administration. Although ABCD increased concentrations of AmB in the reticuloendothelial system, increased toxicity was not observed in these organs. PMID- 1605596 TI - Safety and pharmacokinetics of multiple doses of intravenous ofloxacin in healthy volunteers. AB - The safety and pharmacokinetics of ofloxacin in 48 healthy male volunteers were studied in a two-center, randomized, double-blind, placebo-controlled study. Ofloxacin (200 or 400 mg) or placebo was administered as 1-h infusions every 12 h for 7 days. Plasma ofloxacin concentrations were measured by high-performance liquid chromatography. Mean harmonic half-lives ranged from 4.28 to 4.98 h in the 200-mg dosing group and from 5.06 to 6.67 h in the 400-mg dosing group. Intragroup comparisons of trough plasma concentration-versus-time data from study days 2 through 7 revealed that steady state was achieved by day 2 of both multiple-dose regimens. Intergroup comparisons of mean harmonic half-lives, the areas under the concentration-time curve from 0 to 12 and 0 to 60 h, clearance, and apparent volume of distribution (area method) revealed that the pharmacokinetics of ofloxacin are dose independent. Both ofloxacin dosage regimens appeared to be reasonably well tolerated. The two dosage regimens of ofloxacin, 200 or 400 mg every 12 h, appear to be safe and provide serum drug concentrations in excess of the MICs for most susceptible pathogens over the entire dosing interval. PMID- 1605597 TI - Augmentation of the antibacterial activity of magainin by positive-charge chain extension. AB - Novel analogs of the broad-spectrum antimicrobial peptide magainin-2 were obtained by extension of its chain through addition of segments of positively charged amino acids to either its N or its C terminus and by increasing its helicity. The activity of magainin-2 toward American Type Culture Collection strains of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus was most considerably enhanced by these modifications, whereas, in general, its low hemolytic capacity was not or was only slightly affected. The antibacterial potencies of magainin-2 and its derivatives were more evident following decreases of pH from 7.2 to 6 and 5. PMID- 1605598 TI - In vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against the cyst form of Toxoplasma gondii. AB - The in vitro and in vivo activities of the hydroxynaphthoquinone 566C80 against the cyst form of Toxoplasma gondii were evaluated. In vitro treatment (100 micrograms of 566C80 per ml for 3 days) of cysts isolated from brains of mice infected for 1, 2, 3, 4, or 9 months resulted in loss of viability of the cysts and did not reveal any influence of the duration of in vivo infection on sensitivity to the drug. In vivo experiments to determine the effect of prolonged treatment with 200 mg of 566C80 per kg of body weight per day on cysts in brains of CBA/Ca mice infected with strain ME49 revealed a steady and significant decline in the numbers of cysts compared with the numbers in untreated controls. Histopathology of brains from control mice revealed inflammatory infiltrates around capillaries and in the parenchymas and meninges which were consistently less evident in the brains of treated mice. In addition, cysts were rarely observed in treated mice, whereas extensive inflammation and large numbers of cysts were found throughout the entire brain in control mice infected for the same period. The reduction in the numbers of cysts was evident as early as day 5 of treatment but was more marked at 8 weeks of treatment. The numbers of cysts in the brains of Swiss Webster mice infected for 3 or 6 months also significantly decreased following treatment for 15 or 30 days with the same dose of 566C80. Our results indicate that 566C80 has excellent activity against cysts of T. gondii both in vivo and in vitro and that sensitivity of the cysts to 566C80 is not affected by the duration of the infection in vivo. PMID- 1605599 TI - Pharmacokinetics and distribution over the blood brain barrier of two acyclic guanosine analogs in rats, studied by microdialysis. AB - The free extracellular concentrations of acyclovir and (R)-9-[4-hydroxy-2 (hydroxymethyl)butyl]guanine (H2G) in the blood and in brain tissue of rats were measured in microdialysis samples by high-pressure liquid chromatography with UV detection. The half-life of acyclovir in blood was 2 h, while that of H2G was 28 min. The concentration attained in the brain compared with the concentration in blood was slightly lower for H2G than for acyclovir. The results show that the pharmacokinetic profiles of acyclic nucleosides may vary as a consequence of the structure of the acyclic chain corresponding to the sugar moiety. PMID- 1605600 TI - Survey of Bacteroides fragilis group susceptibility patterns in Canada. AB - The in vitro activities of penicillin, clindamycin, chloramphenicol, metronidazole, piperacillin, piperacillin-tazobactam, ticarcillin, ticarcillin clavulanate, ampicillin-sulbactam, cefoxitin, ceftizoxime, cefotetan, moxalactam, and imipenem against 348 Bacteroides fragilis group isolates collected from six Canadian cities during 1990 were determined by the National Committee for Clinical Laboratory Standards (NCCLS) agar dilution technique. All isolates were susceptible to chloramphenicol, metronidazole, piperacillin-tazobactam, and imipenem. For the other antibiotics tested, the following resistance rates were observed: penicillin, 97%; clindamycin, 9%; piperacillin, 19%; ticarcillin, 31%; ticarcillin-clavulanate, 0.28%; ampicillin-sulbactam, 0.85%; cefoxitin, 26%; ceftizoxime, 15%; cefotetan, 53%; and moxalactam, 17%. Susceptibility profiles to beta-lactam antibiotics varied among the different species tested: B. fragilis and Bacteroides vulgatus demonstrated lower resistance rates than Bacteroides distasonis and indole-positive Bacteroides thetaiotaomicron and Bacteroides ovatus. Ceftizoxime results should be interpreted cautiously, because the MICs obtained with the recommended NCCLS control strain were lower than expected. PMID- 1605601 TI - Glycosylation of macrolide antibiotics in extracts of Streptomyces lividans. AB - Inducible resistance to macrolide antibiotics in Streptomyces lividans involves MGT, a macrolide glycosyl transferase that utilizes UDP-glucose as cofactor. Substrates for MGT include macrolides with 12-, 14-, 15-, or 16-atom cyclic polyketide lactones (as in methymycin, erythromycin, azithromycin, or tylosin, respectively), although spiramycin and carbomycin are not apparently modified. The enzyme is specific for the 2'-OH group of saccharidic moieties attached to C 5 of the 16-atom lactone ring (corresponding to C-5 or C-3 in 14- or 12-atom lactones, respectively). PMID- 1605602 TI - Prevention of indigenous infection of mice with Escherichia coli by nonspecific immunostimulation. AB - We have previously reported that the lethal toxicity of 5-fluorouracil (5-FU) in specific-pathogen-free mice is due to an intestinal infection with indigenous Escherichia coli induced by the drug (K. Nomoto, T. Yokokura, Y. Yoshikai, M. Mitsuyama, and K. Nomoto, Can J. Microbiol. 37:244-247, 1991). In the present study we demonstrate that nonspecific immunostimulation is effective in the protection of mice from the lethal indigenous infection induced by 5-FU. Intravenous or subcutaneous injection of a preparation of heat-killed Lactobacillus casei YIT 9018, a potent nonspecific immunostimulant, into BALB/c mice reduced the lethal toxicity of 5-FU at doses ranging from 338 to 800 mg/kg of body weight if YIT 9018 was injected 7 to 40 days before administration of 5 FU. Systemic infection with E. coli developed in all of the 5-FU-treated control mice 7 days or more after administration of 5-FU in large doses and was accompanied by overgrowth of the bacteria in the intestinal tract. Pretreatment of mice with YIT 9018 resulted in a decreased occurrence of systemic infection with E. coli to levels of 0 to 20% and no significant changes in the population levels of E. coli in the intestinal tract during the 14 days after administration of 5-FU. The levels of leukopenia in the spleen and peripheral blood were lower, and recovery of granulocyte-macrophage precursor cells in the spleen and femur began earlier in the treated animals than in the 5-FU-treated controls. Intravenous transfusion of syngeneic normal bone marrow cells or spleen cells into the mice at an early period after administration of 5-FU diminished markedly the occurrence of the lethal indigenous infection, suggestion that an earlier recovery from chemotherapy-induced myelosuppression is important in the mechanisms of protection of the host from the infection. PMID- 1605603 TI - Chemotherapeutic efficacy of a newly synthesized benzoxazinorifamycin, KRM-1648, against Mycobacterium avium complex infection induced in mice. AB - Newly synthesized benzoxazinorifamycin, KRM-1648, was studied for its in vivo anti-Mycobacterium avium complex (MAC) activities. When the MICs were determined by the agar dilution method with Middlebrook 7H11 agar medium, KRM-1648 exhibited similarly potent in vitro antimicrobial activities against the MAC isolated from AIDS and non-AIDS patients, indicating possible usefulness of KRM-1648 against AIDS-associated MAC infections. KRM-1648 exhibited potent therapeutic activity against experimental murine infections induced by M. intracellulare N-260 (virulent strain) and N-478, which has much weaker virulence. Similarly, KRM-1648 exhibited an excellent therapeutic efficacy against M. intracellulare infection induced in NK-cell-deficient beige mice (as a plausible model for AIDS-associated MAC infection), in which a much more progressed state of gross lesions and bacterial loads at the sites of infection were observed. When the infected beige mice were killed at weeks 4 and 8, obvious therapeutic efficacy was seen on the basis of reduction in the incidence and degree of lung lesions and bacterial loads in the lungs and spleen with infections due to M. intracellulare N-241, N 256, and N-260. In this case, the efficacy was the highest in N-260 infection, followed by strain N-241. When mice were observed until infection-induced death, survival time of the infected beige mice was found to be prolonged by KRM treatment. However, KRM-1648 was not efficacious in suppressing the progression of pulmonary lesions and the increase in bacterial loads at the sites of infection, including lungs and spleen, at the late phase of infection. This may imply some difficulty with chemotherapy for AIDS-associated MAC infection, even with KRM-1648 treatment, which has excellent in vitro and in vivo anti-MAC activities, as shown in present study. PMID- 1605604 TI - Use of a predictor panel for development of a new disk for diffusion tests with cefoperazone-sulbactam. AB - The proper disk mass for diffusion susceptibility tests with cefoperazone sulbactam was determined by using a predictor panel of clinical isolates that included staphylococci and gram-negative bacteria intrinsically susceptible, intrinsically resistant, and of various susceptibilities because of the production of different types and amounts of beta-lactamase. A primary panel of 24 isolates was used to screen various disk masses of cefoperazone and sulbactam in disk diffusion susceptibility tests. Regression analyses were performed for each combination by comparing MICs to zone diameters. Analysis of each component demonstrated that decreasing the disk mass of cefoperazone shifted the regression line to the left while decreasing the disk mass of sulbactam diminished the slope of the line. Ten candidate disks that adequately separated susceptible and resistant strains among the primary panel were identified, and these 10 disks, along with the previously proposed 75/30-micrograms disk, were then tested against an expanded panel of 265 isolates. Results indicated that a 30/20 micrograms cefoperazone-sulbactam disk provided the best separation between susceptible and resistant strains when interpretive criteria of less than or equal to 15 mm for resistance, 16 to 19 mm for moderate susceptibility, and greater than or equal to 20 mm for susceptibility were used. They also identified discrepancies between agar and broth microdilution MICs of sufficient size to warrant separate interpretive criteria for the two methods. Overall, the use of a predictor panel to develop interpretive criteria for susceptibility tests appeared to be a very useful approach, especially when antibiotics designed to be used against drug-resistant organisms are involved. PMID- 1605605 TI - Use of norfloxacin to study colonization ability of Escherichia coli in in vivo and in vitro models of the porcine gut. AB - The colonization resistance conveyed by the intestinal microbiota can prevent colonization of the intestinal system by new strains. In this study, this resistance was partly circumvented by use of the antimicrobial drug norfloxacin. The colonization abilities of two closely related Escherichia coli strains, which were resistant to nalidixic acid and rifampin, respectively, were investigated in minipigs and a two-stage continuous-flow in vitro gut model. Whereas both strains were unable to colonize the intact enteric system in vivo and in vitro, a 3-day norfloxacin treatment modified both systems to allow colonization by the nalidixic acid-resistant strain but not the rifampin-resistant strain. The results indicate the usefulness of norfloxacin to circumvent the normal colonization resistance while keeping a fairly normal microbiota in the gut. The results also indicate that it could be possible to construct in vitro gut models which could distinguish between strains with different gut colonization abilities. Both of these possibilities could come to be used in the study of the colonization and effects in the gut of new bacterial strains, i.e., genetically modified microorganisms. PMID- 1605606 TI - Survey of methicillin-resistant clinical strains of coagulase-negative staphylococci for mecA gene distribution. AB - A total number of 125 methicillin-resistant (MIC, greater than or equal to 16) coagulase-negative Staphylococcus strains isolated in Japan were surveyed for the distribution of the mecA gene, the structural gene for penicillin-binding protein 2', which is the causative genetic element for the intrinsic resistance of methicillin-resistant Staphylococcus aureus. Screening with colony hybridization by using a cloned mecA gene probe revealed that 121 strains (96.8%) belonging to the nine coagulase-negative Staphylococcus species (S. epidermidis, S. haemolyticus, S. saprophyticus, S. sciuri, S. simulans, S. hominis, S. capitis, S. warneri, and S. caprae) carried mecA in their genome, indicating wide distribution of the gene among coagulase-negative Staphylococcus species. Most (93.4%) of the mecA-carrying strains were producers of penicillinase. Four strains, including two S. haemolyticus and two S. saprophyticus strains, did not carry mecA in spite of their resistance to methicillin. One of them was of low level resistance (MIC, 16), but three of them had moderate- to high-level resistance to methicillin (MIC, 64). Analysis of gel electrophoretic banding patterns of penicillin-binding proteins of these strains showed absence of penicillin-binding protein 2' but some alterations in signal intensities of the other penicillin-binding proteins. The result indicated that about 3% of methicillin-resistant coagulase-negative staphylococci in these hospitals had a resistance mechanism different from that associated with the production of penicillin-binding protein 2', as has been reported in the case of a borderline methicillin-resistant strain of S. aureus. PMID- 1605607 TI - Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4 carboxamide, and 6'-(R)-6'-C-methylneplanocin A against several ortho- and paramyxoviruses. AB - 5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C methylneplanocin A (TJ13025) are two novel antiviral agents which are targeted against IMP dehydrogenase and S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities against various strains of orthomyxoviruses (influenza virus) and paramyxoviruses (parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus) in vitro. EICAR was 10- to 59-fold more active than ribavirin and TJ13025 was 32- to 330-fold more active than ribavirin against parainfluenza virus types (2 and 3), mumps virus, and measles virus. EICAR was also more active than ribavirin against respiratory syncytial virus and influenza virus, whereas TJ13025 was virtually inactive against these viruses. The 50% virus-inhibitory concentrations of EICAR and TJ13025 were generally within the 0.1- to 1-microgram/ml range. Although the compounds did not prove cytotoxic to stationary host cells (HeLa, Vero, MDCK, and LLCMK2) at a concentration of 200 micrograms/ml, concentrations of 4 to 13 micrograms/ml inhibited the growth of dividing cells. EICAR and TJ13025 should be further pursued as candidate drugs for the treatment of ortho- and paramyxovirus infections. PMID- 1605608 TI - Characterization of four beta-lactamases produced by Staphylococcus aureus. AB - Staphylococcus aureus produces four types of beta-lactamase (A, B, C, and D). To investigate the effect of specific beta-lactamase type upon staphylococcal resistance, each beta-lactamase was purified to homogeneity, and the Michaelis constants (Km values) and turnover numbers (kcat values) for various penicillin and cephalosporin substrates were determined. Whereas Km values of the four beta lactamases were comparable for penicillin G, cephalothin, and cefamandole, the type A and D enzymes exhibited greater affinity than the type B and C beta lactamases for nitrocefin, cefazolin, and cephapirin. Conversely, the type B and C beta-lactamases exhibited greater kcat values than the type A and D enzymes against most of the cephalosporin agents, excluding nitrocefin. In contrast to earlier reports suggesting that the type B beta-lactamase is relatively inefficient in hydrolyzing penicillin G, we found only minor differences in the specific activities and kcat values of the type A, B, and C beta-lactamases. The type D beta-lactamase was distinctly less active against penicillin G, however, exhibiting only 15 to 25% of the kcat values of the other beta-lactamases. More than a 2,000-fold difference between the relative efficiencies of hydrolysis (kcat/Km) of cefazolin and cefuroxime by the type A beta-lactamase exists. This greatly exceeds the 60-fold difference in the stability of penicillin G and cefazolin with the same enzyme. Whereas the isoelectric points of the type A, B, and C beta-lactamases were similar, the value for the type D beta-lactamase was distinguishably lower (10.1 for types A, B, and C and 9.7 for type D). We conclude that marked differences in the stability of commonly used beta-lactams to hydrolysis by the staphylococcal beta-lactamases are present. This heterogeneity and the clinical implication thereof need to be considered in the antibiotic management of staphylococcal infection. PMID- 1605609 TI - Pharmacokinetic disposition and bactericidal activities of cefepime, ceftazidime, and cefoperazone in serum and blister fluid. AB - Cefepime is a new broad-spectrum cephalosporin with excellent gram-positive and gram-negative activity including activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacter cloacae. The pharmacokinetic disposition of cefepime is similar to that of ceftazidime. We compared the pharmacokinetic characteristics and the extent and duration of bactericidal activity in serum and suction-induced blister fluid after single 2-g intravenous doses of cefepime, ceftazidime, and cefoperazone given to healthy subjects. One clinical isolate each of E. cloacae, P. aeruginosa, and S. aureus was used to assess bactericidal activity. Results of the pharmacokinetic analysis were similar to previously reported data for these drugs. The high serum protein binding of cefoperazone (approximately 90%) contributed to poor blister fluid penetration. The other drugs penetrated well into this fluid compartment. Cefepime showed significantly greater bactericidal activity in serum and blister fluid against E. cloacae than the other study drugs, ceftazidime was significantly better in serum and blister fluid against P. aeruginosa, and cefoperazone was significantly better against S. aureus only in serum. None of the study drugs had significant bactericidal activity in blister fluid against S. aureus. Cefepime is a promising antimicrobial agent for the treatment of infections due to E. cloacae. PMID- 1605610 TI - Efficacy of ticarcillin-clavulanic acid for treatment of experimental Staphylococcus aureus endocarditis in rats. AB - The efficacy of ticarcillin-clavulanic acid was compared with the efficacies of standard antistaphylococcal agents (flucloxacillin, oxacillin, nafcillin, and vancomycin) and ticarcillin in an experimental model of Staphylococcus aureus endocarditis. Therapy was either initiated soon (8 h) after infection, when numbers of bacteria in aortic valve vegetations were relatively low (approximately 6 to 8 log10 CFU/g), or delayed until 24 h after infection, when the vegetations usually contained greater than 9 log10 CFU/g. Doses of the antibiotic were selected to produce peak concentrations in rat serum similar to those achievable in humans after administration of parenteral therapeutic doses. Ticarcillin-clavulanic acid was more effective overall than ticarcillin alone against endocarditis caused by beta-lactamase-producing strains of S. aureus, illustrating the beta-lactamase-inhibitory activity of clavulanic acid in vivo. Ticarcillin-clavulanic acid was as effective as the standard antistaphylococcal beta-lactam agents flucloxacillin, oxacillin, and nafcillin in these infections, whereas vancomycin was generally less active. These results illustrate the clinical potential of ticarcillin-clavulanic acid in the prophylaxis or therapy of severe staphylococcal infections. PMID- 1605611 TI - Genetic basis of tetracycline resistance in clinical isolates of Listeria monocytogenes. AB - The genetic basis of tetracycline resistance was studied in 25 clinical isolates of Listeria monocytogenes. Resistance to tetracycline was associated with resistance to minocycline and due to the presence of the tet(M) gene in 24 strains. Association of tet(M) with int-Tn, the gene encoding the protein required for the movements of Tn1545-like conjugative transposons, was found in all strains. Cotransfer of tet(M) and int-Tn among L. monocytogenes cells and from L. monocytogenes to Enterococcus faecalis was detected in 7 of the 12 strains studied at frequencies similar to those obtained with the prototype element Tn1545. tet(L), the second most prevalent tetracycline resistance gene in enterococci and streptococci, was detected in the remaining strain, where it was borne by a 5-kb plasmid. These observations indicate that two types of movable genetic elements, transposons and plasmids, in enterococci and streptococci are responsible for emergence of drug resistance in L. monocytogenes. PMID- 1605612 TI - Identification of a ROB-1 beta-lactamase in Haemophilus ducreyi. AB - A collection of 100 clinical isolates of Haemophilus ducreyi from Thailand were all found to harbor a 5.4-kb plasmid, designated pTH126, which was shown to contain the bla ROB-1 gene. Restriction enzyme analysis and DNA-DNA hybridization studies confirmed that pTH126 was similar to the ROB-1 beta-lactamase plasmid pVM105 from Actinobacillus pleuropneumoniae. In approximately one-half of the isolates, pTH126 was found together with pHD131, which mediates TEM-1 beta lactamase production. PMID- 1605613 TI - Use of fluoroquinolones for prophylaxis of murine Pneumocystis carinii pneumonia. AB - We compared the prophylactic activities of six fluoroquinolones against Pneumocystis carinii pneumonia in immunosuppressed rats. Pefloxacin was the only agent which was as effective as the reference drug trimethoprim-sulfamethoxazole. Clinical trials with pefloxacin in patients at risk for P. carinii pneumonia appear to be justified. PMID- 1605614 TI - Utilization of pulse oximetry for the study of the inhibitory effects of antiviral agents on influenza virus in mice. AB - Pulmonary disease in mice induced by influenza virus was monitored by measurement of oxygen saturation (SaO2) in blood with a pulse oximeter. The SaO2 declined in inverse proportion to the viral inoculum. The known antiviral agent ribavirin inhibited the SaO2 decline, prevented death, lowered lung consolidation, and reduced the level of recoverable virus. Pulse oximetry is an effective means of monitoring murine influenzal disease and can be used in the study of potential antiviral drugs. PMID- 1605615 TI - Effect of cyclodextrin on the pharmacology of antifungal oral azoles. AB - Concentrations of oral azoles in serum were compared in a single-dose pharmacologic study in mice. When hydroxypropyl-beta-cyclodextrin was used as a carrier and compared with a standard carrier, polyethylene glycol, drug concentrations determined by bioassay showed that the peak concentration and area under the concentration-time curve were greatly enhanced for itraconazole and saperconazole; moderately enhanced for ketoconazole; but negligibly affected for fluconazole, miconazole, and SCH 42427. PMID- 1605616 TI - Renal dehydropeptidase-I stability of LJC 10,627, a new carbapenem antibiotic. AB - LJC 10,627 is a new parenteral carbapenem antibiotic. LJC 10,627 stability against human renal dehydropeptidase-I was compared with that of imipenem. Hydrolysis of this compound was not detectable by spectrophotometrical assay. Even after a 2-h incubation of antibiotics with this enzyme at 30 degrees C, the concentration of LJC 10,627 remained at 92.3% of the initial concentration, whereas imipenem completely disappeared. Thus, it was found that this compound was highly stable against human renal dehydropeptidase-I. Furthermore, LJC 10,627 had a low affinity for this enzyme, as indicated by the high Ki value (0.38 mM). PMID- 1605617 TI - The multidrug efflux transporter of Bacillus subtilis is a structural and functional homolog of the Staphylococcus NorA protein. AB - The Bacillus subtilis multidrug efflux transporter Bmr demonstrates 44% amino acid sequence identity with a product of the Staphylococcus aureus gene norA, which is responsible for clinically relevant resistance to fluoroquinolones. We show here that overexpression of bmr in B. subtilis provides strong resistance to fluoroquinolones that can be reversed by reserpine, an inhibitor of Bmr. PMID- 1605618 TI - Comparison of antifungal activity of amphotericin B deoxycholate suspension with that of amphotericin B cholesteryl sulfate colloidal dispersion. AB - Complexing amphotericin B (AmB) with lipids or entrapping it in liposomes may increase its efficacy by reducing toxicity and affecting distribution. However, depending on the lipids involved, interference with antifungal activity has been shown. We compared the in vitro activity of AmB colloidal dispersion by cholesteryl sulfate (ABCD) to the standard AmB deoxycholate suspension (ABDS) against 41 isolates of 15 pathogenic species. Broth dilution MIC and minimum fungicidal concentration (MFC) ranges were similar, and the same number of isolates had lower MICs and MFCs with one drug as with the other. Differences between species were noted. In less than a third of comparisons, there were large (fourfold or more) decreases in ABCD activity relative to that of ABDS, and in approximately 1/10, there were large increases. Thus, ABCD complexing variably affects AmB activity. As ABCD pharmacokinetics and toxicology differ from those of ABDS, the significance of these results for in vivo activity needs to be determined. PMID- 1605619 TI - Inhibition of norfloxacin absorption by dairy products. AB - Seven healthy subjects received, after an overnight fast, a single 200-mg oral dose of norfloxacin with water, whole milk, and unflavored yoghurt. Coadministration of milk or yoghurt reduced the extent of norfloxacin absorption and the mean peak concentration in plasma by approximately 50%. Taking of norfloxacin with these liquid dairy products should be avoided. PMID- 1605620 TI - Inhibitory effects of polyethers on human immunodeficiency virus replication. AB - We examined the inhibitory activities of 10 polyether antibiotics on human immunodeficiency virus (HIV) type 1. These compounds caused concentration dependent inhibition of HIV replication in primary infected cultures of human T lymphoblastoid H9 cells. The ratio of 50% effective concentrations for cellular cytotoxicity (MTT assay) to antiviral activity (reverse transcriptase assay) was over 5. Anti-HIV activity was also observed in cultures of monocytic lineage U937 cells chronically infected with HIV. PMID- 1605621 TI - In vitro and in vivo activities of SCH 42427, the active enantiomer of the antifungal agent SCH 39304. AB - SCH 39304, a new triazole antifungal agent, is a 50:50 racemic mixture of two enantiomers, SCH 42427 and SCH 42426. The activities of these three compounds were compared in a series of in vitro and in vivo experiments. SCH 42427 was twofold more active in vitro against a variety of yeasts and dermatophytes than SCH 39304, while SCH 42426 was inactive (MICs greater than 64 micrograms/ml). In a systemic Candida albicans infection in mice, SCH 42427 administered orally (p.o.) (50% protective dose [PD50], 0.17 mg/kg of body weight; 50% effective dose, [ED50], 0.47 mg/kg) had greater efficacy than SCH 39304 (PD50, 0.21 mg/kg; ED50, 0.62 mg/kg) and SCH 42426 (greater than 100 mg/kg for PD50 and ED50). In a pulmonary Aspergillus flavus infection in mice, SCH 42427 p.o. (PD50, 13 mg/kg) was also more effective than SCH 39304 (18 mg/kg) and SCH 42426 (greater than 250 mg/kg). In a C. albicans vaginal infection in hamsters, SCH 42427 p.o. (ED50, 3.5 mg/kg) was more active than SCH 39304 (8.5 mg/kg) and SCH 42426 (320 mg/kg). Following topical administration, against a Trichophyton mentagrophytes infection in guinea pigs, SCH 42427 was about 2-fold more active than SCH 39304 and about 100-fold more active than SCH 42426. These and other results indicated that SCH 42427 is the active enantiomer, responsible for all the antifungal activity observed with SCH 39304. PMID- 1605622 TI - Conjugal transfer of plasmid DNA from Enterococcus faecalis to Escherichia coli in digestive tracts of gnotobiotic mice. AB - We have studied the transfer of the conjugative shuttle plasmid pAT191, which confers resistance to kanamycin, from Enterococcus faecalis to Escherichia coli in the digestive tracts of six gnotobiotic mice. Colonies of E. coli resistant to kanamycin were isolated from the feces of two mice, respectively, on days 25 and 35 after the beginning of the experiment and never thereafter. The transfer frequency of pAT191, expressed as the number of transconjugants per donor cell isolated from intestines of sacrificed mice, was 3 x 10(-9). These results indicate that conjugation is a mechanism that could account for the resistance gene flux from gram-positive to gram-negative bacteria observed in nature. PMID- 1605623 TI - Rationalization of the effects of compatible solutes on protein stability in terms of thermodynamic nonideality. AB - Inhibition by compatible solutes such as proline and glycine betaine of the rate of coagulation, at 60 degrees C, of bovine serum albumin in 0.1 M acetate buffer, pH 5, is used as a model system to substantiate the concept that the production of high concentrations of osmolytes by plants and other organisms in response to stress (e.g., drought) results in stabilization of native enzyme structures via nonspecific excluded volume effects. The paradoxical situation whereby this effect of compatible solutes counters to some extent the protein-precipitating effect of poly(ethylene glycol) is also seemingly resolved. PMID- 1605624 TI - Binding of human tumor necrosis factor alpha to multimeric complementary peptides. AB - A peptide with binding properties for tumor necrosis factor (TNF alpha) sequence 144-157 has been designed, using a computer-assisted method able to create peptide sequences hydropathically complementary to a given sequence. The complementary peptide was synthesized in a multimeric form starting from an octadentate polylysine core, to facilitate its immobilization and to provide interaction multivalency. Once immobilized on a solid support to prepare an affinity column, it recognized the target TNF144-157 peptide selectively from crude peptide mixtures containing TNF fragments encompassing the entire TNF alpha sequence. Similar selectivity and specificity were shown for full-length recombinant TNF alpha, allowing its purification from crude Escherichia coli extracts. The octameric complementary peptide preserved its recognition properties for TNF alpha and biotinylated TNF alpha even after coating on microtiter plates. Competitive binding occurred with unlabeled TNF alpha in the range between 0.01 and 10 micrograms/ml, in the presence of detergent such as 0.05% Tween 20 and in the presence of 1% normal goat serum. The effect of complementary peptide multimerization was evidenced by its enhanced binding affinity for TNF alpha, which exists in solution as a trimer, while the target TNF[144-157] peptide was recognized with much lower strength. The dissociation constant for interaction with TNF alpha was close to 10 nM, allowing its easy detection by solid phase assays in concentrations as low as 10 pmol/ml. PMID- 1605625 TI - Investigation of the substrate binding and catalytic groups of the P-C bond cleaving enzyme, phosphonoacetaldehyde hydrolase. AB - Kinetic studies with substrate analogs and group-directed chemical modification agents were carried out for the purpose of identifying the enzyme-substrate interactions required for phosphonoacetaldehyde (P-Ald) binding and catalyzed hydrolysis by P-Ald hydrolase (phosphonatase). Malonic semialdehyde (Ki = 1.6 mM), phosphonoacetate (Ki = 10 mM), phosphonoethanol (Ki = 10 mM), and fluorophosphate (Ki = 20 mM) were found to be competitive inhibitors of the enzyme but not substrates. Thiophosphonoacetaldehyde and acetonyl phosphonate underwent phosphonatase-catalyzed hydrolysis but at 20-fold and 140-fold slower rates, respectively, than did P-Ald. In the presence of NaBH4, acetonyl phosphonate inactivated phosphonatase at a rate exceeding that of its turnover. Sequence analysis of the radiolabeled tryptic peptide generated from [3 3H]acetonylphosphonate/NaBH4-treated phosphonatase revealed that Schiff base formation had occurred with the catalytic lysine. From the Vm/Km and Vm pH profiles for phosphonatase-catalyzed P-Ald hydrolysis, an optimal pH range of 6-8 was defined for substrate binding and catalysis. The pH dependence of inactivation by acetylation of the active site lysine with acetic anhydride and 2,4-dinitrophenyl acetate evidenced protonation of the active site lysine residue as the cause for activity loss below pH 6. The pH dependence of inactivation of an active site cysteine residue with methyl methanethiol-sulfonate indicated that deprotonation of this residue may be the cause for the loss of enzyme activity above pH 8. PMID- 1605627 TI - A novel human phosphotransferase highly specific for adenosine. AB - A novel nucleoside phosphotransferase, referred to as adenosine phosphotransferase (Ado Ptase), was partially purified 1230-fold from human placenta. This enzyme differed from other known nucleoside phosphotransferases in its substrate specificity. Using AMP as the phosphate donor, it readily phosphorylated Ado. Changes in the sugar moiety were tolerated. dAdo and ddAdo were phosphate acceptors and dAMP was a donor. No other nucleotide or nucleoside common in nature displayed appreciable activity as donor or acceptor substrate, respectively. In the absence of nucleoside, the enzyme catalyzed the hydrolysis of AMP, typical of other nucleoside phosphotransferases. However, in the presence of Ado, little, if any, hydrolysis occurred. Ado Ptase had an absolute requirement for a metal cation, with Mg2+ and, to a lesser extent, Mn2+ fulfilling this requisite. The apparent Km for Ado was 0.2 mM. However, the donor AMP displayed cooperativity in both transfer and hydrolytic reactions. This cooperativity was eliminated by nucleotides, 2,3-diphosphoglycerate, and inorganic phosphate. ADP and 2,3-diphosphoglycerate were especially potent. In the presence of these effectors, the apparent Km for AMP was 3.0 mM in the transfer reaction and 4.0 mM in the hydrolytic reaction. Kinetic data suggest that there are two nucleotide binding sites on Ado Ptase, one for the donor, the other for an effector. AMP appeared to bind to both sites. Although this novel enzyme might play a role in the anabolism of nucleoside analogues, the normal physiological role of this nucleoside phosphotransferase is not understood. PMID- 1605626 TI - Subtilisin cleavage of tubulin heterodimers and polymers. AB - Native pig brain tubulin in heterodimer or polymer form was subjected to limited proteolysis by subtilisin, which is known to cleave at accessible sites within the last 50 amino acids of the highly variable carboxyl-termini of the alpha and beta subunits. Heterodimeric tubulin or tubulin polymerized in the presence of 4 M glycerol or taxol was used in these experiments. Digested tubulin was purified by cycles of polymerization and depolymerization, ammonium sulfate precipitation, or ion-exchange chromatography in the absence or presence of nonionic detergent; however, smaller cleaved products of about 34,000 to 40,000 MW remained associated with the major cleaved subunits, alpha' and beta', under all purification conditions. In order to determine the effect of subtilisin cleavage on tubulin heterogeneity, purified native or subtilisin-cleaved tubulin was subjected to isoelectric focusing, followed by SDS-PAGE. The total number of isotypes was reduced from 17-22 for native alpha,beta tubulin to 7-9 for subtilisin-cleaved alpha',beta' tubulin. When tubulin heterodimers were cleaved, a single major beta' isotype was evident; however, when tubulin polymerized in 4 M glycerol was cleaved, two major beta' isotypes were found. Monoclonal antibodies that recognize a beta carboxyl-terminal peptide, residues 410-430, reacted with both major beta' isotypes, indicating that subtilisin cleavage occurred within the last 20 of the 450 amino acids. In order to establish whether this difference was in fact associated with polymer or heterodimer forms of tubulin, digestion was carried out in the presence of taxol, which stabilizes tubulin polymers. A single major beta' isotype different from the cleaved heterodimer, but coincident with one of the bands of the cleaved glycerol-induced polymers, was found when taxol-treated tubulin was digested. This result suggests the presence of more than one subtilisin site in the beta subunit, near residues 430-435, with different accessibility to the enzyme in the heterodimer and polymer form. PMID- 1605628 TI - Purification and characterization of prostaglandin F synthase from bovine liver. AB - Prostaglandin D2 11-ketoreductase activity of bovine liver was purified 340-fold to apparent homogeneity. The purified enzyme was a monomeric protein with a molecular weight of about 36 kDa, and had a broad substrate specificity for porstaglandins D1, D2, D3, and H2, and various carbonyl compounds (e.g., phenanthrenequinone and nitrobenzaldehyde, etc.). Prostaglandin D2 was reduced to 9 alpha,11 beta-prostaglandin F2 and prostaglandin H2 to prostaglandin F2 alpha with NADPH as a cofactor. Phenanthrenequinone competitively inhibited the reduction of prostaglandin D2, while it did not inhibit that of prostaglandin H2. Moreover, chloride ion stimulated the reduction of prostaglandin D2 and carbonyl compounds, while it had no effect on that of prostaglandin H2. Besides, the enzyme was inhibited by flavonoids (e.g., quercetin) that inhibit carbonyl reductase, but was not inhibited by barbital and sorbinil, which are the inhibitors of aldehyde and aldose reductases, respectively. These results indicate that the bovine liver enzyme has two different active sites, i.e., one for prostaglandin D2 and carbonyl compounds and the other for prostaglandin H2, and appears to be a kind of carbonyl reductase like bovine lung prostaglandin F synthase (Watanabe, K., Yoshida, R., Shimizu, T., and Hayaishi, O., 1985, J. Biol. Chem. 260, 7035-7041). However, the bovine liver enzyme was different from prostaglandin F synthase of bovine lung with regard to the Km value for prostaglandin D2 (10 microM for the liver enzyme and 120 microM for the lung enzyme), the sensitivity to chloride ion (threefold greater activation for the liver enzyme) and the inhibition by CuSO4 and HgCl2 (two orders of magnitude more resistant in the case of the liver enzyme). These results suggest that the bovine liver enzyme is a subtype of bovine lung prostaglandin F synthase. PMID- 1605629 TI - Role of oxygen in oxidation of lipid and protein during ischemia/reperfusion in isolated perfused rat lung. AB - Considerable evidence has accumulated that oxygen free radicals play a major role in ischemic injury, particularly when followed by reperfusion. Few reports have demonstrated the occurrence of oxidative damage during the ischemic period, itself. Our laboratory has demonstrated that events occurring during an ischemic period with adequate oxygen supply can mimic the "oxygen paradox," using lipid peroxidation as an index of oxidative stress and lung edema as an index of tissue injury. The present study compares lipid peroxidation and oxidation of soluble (100,000g supernatant) protein during ischemia and reperfusion in isolated rat lung model perfused with artificial medium and ventilated with varying alveolar oxygen tension. Protein oxidation was determined by a modified dinitrophenylhydrazine (DNPH) method using Sephadex G-25 column chromatography to isolate the DNPH bound proteins. Global ischemia was produced by discontinuing perfusion while ventilation continued with gas mixtures containing 5% CO2 and a fixed oxygen concentration between 0 and 95%. After 1 h ischemia in the isolated rat lung ventilated with 20% oxygen, protein carbonyls and thiobarbituric acid reactive substances (TBARS) increased significantly compared with controls. These changes were more pronounced after 60 min of reperfusion with 95% oxygen in the ventilation gas. With 0% oxygen (95% nitrogen and 5% CO2) content of the ventilating gas during ischemia, TBARS and protein carbonyls remained at the control level. The wet/dry weight ratio showed changes parallel to the indices of tissue oxidation. The presence of 5,8,11,14-eicosatetraynoic, an inhibitor of cyclooxygenase and lipoxygenase pathways, in the perfusate had no effect on the generation of protein carbonyls although inhibition of lipid peroxidation was demonstrated. This implies that the oxidation of soluble protein is not mediated by the eicosanoid metabolic cascade. These data indicate that oxidative processes occur during ischemia and are dependent on the alveolar oxygen concentration. Oxidation of soluble protein can be used as an index of oxidative damage during lung ischemia and reperfusion. PMID- 1605630 TI - cDNA clone to chick corneal chondroitin/dermatan sulfate proteoglycan reveals identity to decorin. AB - A 1.6-kb cDNA clone was isolated by screening a library prepared from chick corneal mRNA with a cDNA clone to bovine decorin. The cDNA contained an open reading frame coding for a M(r) 39,683 protein. A 19-amino-acid match with sequence from the N-terminus of core protein from the corneal chondroitin/dermatan sulfate proteoglycan confirmed the clone as a corneal proteoglycan and the homology with human and bovine decorin confirmed its identity as decorin. Structural features of the deduced sequence include a 16 amino-acid signal peptide, a 14-amino-acid propeptide, cysteine residues at the N and C-terminal regions, and a central leucine-rich region (comprising 63% of the protein) containing nine repeats of the sequence LXXLXLXXNXL/I. Chick decorin contains three variations of this sequence that are tandemly linked to form a unit and three units tandemly linked to form the leucine-rich region. The presence of beta bend amino acids flanking the units may serve to delineate the units as structural elements of the leucine-rich region. Sequence homology within the repeats and the spacing of the repeats suggest that this region arose by duplication. Chick decorin primarily differs from mammalian decorins in the 19 amino-acid sequence that starts the N-terminus of the core protein. Within this region, the serine that serves as a potential acceptor for the chondroitin/dermatan sulfate side chain is preceded by a glycine instead of being followed by a glycine as it is in the mammalian decorins and all other mammalian proteoglycans. PMID- 1605631 TI - Identification of prolactin receptors in hepatic nuclei. AB - Prolactin is a trophic hormone which may act directly at the hepatocyte nucleus. In this study, specific prolactin binding sites were sought in purified rat liver nuclei. Saturable and specific, high affinity 125I-prolactin binding sites were demonstrated to be on or within the nucleus. Prolactin binding was competitively inhibited by rat and ovine prolactins but not by rat growth hormone. Using immunogold electron microscopy, we detected prolactin receptors throughout the nucleus, in association with heterochromatin. Furthermore, endogenous immunoreactive prolactin was demonstrated to be within hepatic nuclei. We conclude that rat liver nuclei possess prolactin binding sites which likely participate in hormone-directed growth processes. PMID- 1605632 TI - Thermodynamic elucidation of solute-induced lipid interdigitation phase: lipid interactions with hydrophobic versus amphipathic species. AB - Comparative thermodynamic studies on the interactions of aqueous dispersions of dipalmitoyl phosphatidylcholine (DPPC) bilayer vesicles with hydrophobic and amphipathic species were conducted to elucidate the nature of the solute-induced interdigitated lipid phase. Cyclohexanol, a strong hydrophobic species, lowers the temperature (tm) of the lipid main phase transition from the gel to the liquid-crystalline phase. Unlike ethanol (an amphipathic species), as reported previously, cyclohexanol does not exert a biphasic effect on tm (lowering tm at lower concentrations and raising tm at higher concentrations). At cyclohexanol greater than or equal to 15.4 mg/ml or 0.154 M, the thermogram of DPPC vesicles exhibits a small transition adjacent to the main phase transition but at a lower temperature. In contrast, ethanol does not promote such a small transition. Furthermore, the enthalpy (delta H) of the transition is increased in the presence of cyclohexanol. The sign of the enthalpy change (delta H-delta Ho) is positive and that of the free energy change (delta G-delta Go) is negative, a characteristic of solute-solute hydrophobic interaction. In contrast, DPPC bilayer vesicles exhibit both (delta H-delta Ho) and (delta G-delta Go) greater than 0 in the presence of ethanol in a concentration range where lipid vesicles exist in an interdigitated phase. To support the above distinct thermodynamic observations, fluorescence steady-state polarization (P) measurements were also performed. At the temperature below tm, the value of P decreases as cyclohexanol concentration increases, while a biphasic effect on P was found in the presence of ethanol. These findings support the postulation that the solute-induced interdigitated lipid phase requires the solute molecule to be amphipathic in nature. PMID- 1605633 TI - Theoretical study of oxyhemocyanin active site: a possible insight on the first step of phenol oxidation by tyrosinase. AB - Extended Huckel theory calculations have been carried out on a model of the oxyhemocyanin active site that includes six imidazoles, the two copper cations, and a dioxygen molecule. The results obtained for the very likely mu-eta 2:eta 2 arrangement of the dioxygen molecule show that the most favorable orientation of O2 is such that the two long Cu-N coordination bonds are perpendicular to the plane formed by the two metal atoms and O2. This arrangement leads to pentacoordinated coppers with a distorted square pyramidal geometry. The molecular electrostatic potential maps of the complexes exhibit a potential well located close to the peroxo anion midbond. The dependence of the energy and of the molecular electrostatic maps on the precise orientation and location of the imidazole rings has been investigated. These results, which show the important role played by the third remote imidazole ligand, are discussed in relation with the first step of tyrosinase-mediated phenol oxidation. PMID- 1605634 TI - Characterization of ribonuclease P isolated from rat liver cytosol. AB - Rat liver ribonuclease P was isolated from a cytosolic fraction and shown to have optimal activity in the presence of 1 mM MgCl2 and 150-200 mM KCl using Escherchia coli pre-tRNA(Tyr) as substrate. In cesium sulfate isopycnic density gradients, the enzyme had a buoyant density of 1.36 g/ml, indicating that it is a ribonucleoprotein complex. Analysis of the RNAs in the enzyme sample purified through two successive Cs2SO4 density gradient steps revealed the copurification of two major species of RNA (RRP1 and RRP2) along with several less abundant RNAs. Rat liver ribonuclease P activity was insensitive to micrococcal nuclease pretreatment. However, the nuclease-treated preparations contained several incompletely degraded RNA species that may have been sufficient to support the ribonuclease P activity. When RNase A was substituted for micrococcal nuclease, the ribonuclease P activity was diminished by greater than 90%, suggesting the requirement for an RNA subunit for activity. PMID- 1605635 TI - Horseradish peroxidase-catalyzed aerobic oxidation and peroxidation of indole-3 acetic acid. I. Optical spectra. AB - A study of the indole-3-acetate reaction with horse-radish peroxidase, in the absence or presence of hydrogen peroxide, has been performed, employing rapid scan and conventional spectrophotometry. We present here the first clear spectral evidence, obtained on the millisecond time scale, indicating that at pH 5.0 and for high [enzyme/substrate] ratios peroxidase compound III is formed. Most, if not all, of the compound III is formed by oxygenation of the ferrous peroxidase. There is an inhibitory effect of superoxide dismutase and histidine on compound III formation which indicates the involvement of the active oxygen species superoxide and singlet oxygen. It is concluded that the oxidation of indole-3 acetate by horseradish peroxidase at pH 5.0 proceeds through compound III formation to the catalytically inactive forms P-670 and P-630. A reaction path in which the enzyme is directly reduced by indole-3-acetate might be involved as an initiation step. Rapid scan spectral data, which indicate differences in the formation and decay of enzyme intermediate compounds at pH 7.0, in comparison with those observed at pH 5.0, are also presented. At pH 7.0 compound II is a key intermediate in oxidation--peroxidation of substrate. Mechanisms of reactions consistent with the experimental data are proposed and discussed. PMID- 1605636 TI - Regulation of protein degradation in normal and transformed human bronchial epithelial cells in culture. AB - Protein degradation rates are decreased in some transformed cells of mesenchymal origin. We have tested the generality of this phenomenon and evaluated the role of the lysosomes in this down-regulation. To this end we have compared the induction of lysosomal protein degradation among normal, transformed (BEAS-2B), and transformed tumorigenic (BZR, Calu-1) human bronchial epithelial cells in culture. Serum and/or nutrient deprivation, cell confluency, and Ca2+ were used to modulate lysosomal protein degradation. Protein degradation and synthesis were determined by the release or incorporation of [14C]valine in the cells. Autophagic degradation of cytoplasm by lysosomes was evaluated by ultrastructural morphometry. Basal protein degradation was lower (27%) in two of the transformed cell lines (BEAS-2B and BZR). Incorporation of [14C]valine label was raised approximately 4-fold in the transformed cells. Nutrient deprivation stimulated protein degradation equally (2-fold) in transformed and normal cells. Postconfluency increased (1.5-fold) basal protein degradation in Calu-1 cells and a marked enhancement (4-fold) of degradation occurred during nutrient deprivation. Culture of normal human bronchial epithelial cells in high Ca2+ caused phenotypic changes and increased (30%) the degradation of protein induced by nutrient deprivation. In Calu-1, high Ca2+ caused only phenotypic changes. The volume density (Vd) of autophagic vacuoles and dense bodies in the transformed cells was lower under basal conditions but increased markedly during nutrient deprivation. A marked accumulation of lysosomes also occurred in transformed cells during postconfluency. We conclude that cell transformation lowers basal protein degradation in some human epithelial cells. Lysosomal proteolysis of transformed cells is not down-regulated and can be markedly enhanced during nutritional deprivation by the autophagic degradation pathway. PMID- 1605637 TI - Effects of testosterone and estrogen on hepatic levels of cytochromes P450 2C7 and P450 2C11 in the rat. AB - The effects of exogenous hormone treatment on the expression of cytochromes P450 2C7 and P450 2C11 were studied in neonatally gonadectomized and sham-operated male and female rats. Hepatic levels of cytochrome P450 2C7 were found to be two- to threefold higher in intact adult female versus male rats. Neonatal gonadectomy resulted in a reversal of the relative cytochrome P450 2C7 levels in male and female animals at maturity. Expression of this isozyme was restored in ovariectomized females by estradiol treatment. Furthermore, neonatal and/or pubertal administration of estradiol to intact male rats induced cytochrome P450 2C7 to adult female levels. On the other hand, administration of testosterone at all times examined had no effect in intact female rats, but decreased cytochrome P450 2C7 to normal levels in neonatally castrated males treated during adulthood. Neonatal testosterone treatment also increased hepatic cytochrome P450 2C7 content in both ovariectomized females and intact males. These results indicate that estrogen is required for full expression of cytochrome P450 2C7 while the effect of testosterone is ambiguous. In comparison, neonatal gonadectomy of male rats abolished the adult expression of cytochrome P450 2C11. Normal levels were restored only by treatment with testosterone during adulthood. Neonatal testosterone treatment did not induce cytochrome P450 2C11 levels in gonadectomized rats of either sex. In contrast, neonatal estrogen treatment suppressed cytochrome P450 2C11 expression in intact adult male rats to the same extent as neonatal castration. These results indicate that androgen exposure during the adult, and not the neonatal, phase is essential for full expression of cytochrome P450 2C11. PMID- 1605638 TI - Rat lung polycholorinated biphenyl-binding protein: effect of glucocorticoids on the expression of the Clara cell-specific protein during fetal development. AB - Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. The expression of this Clara cell-specific, PCB-binding protein (PCB-BP) during the fetal development of the rat lung was studied by means of ligand binding and a monospecific antiserum. The PCB-BP and specific 4,4'-bis([3H]methylsulfony)-2,2',5,5'-tetrachlorobiphenyl binding was first detected on gestational Day 19 and subsequently the levels of PCB-BP and specific ligand binding increased as a function of gestational age. The start site of transcription for the rat PCB-BP gene was determined by primer extension analysis and the information thus obtained was used to develop a quantitative assay for the corresponding mRNA based on solution hybridization and S1 nuclease mapping. The appearance of PCB-BP mRNA during fetal lung development preceded the detection of immunoreactive protein and ligand binding by 1 day. By Day 21, the level of PCB-BP mRNA was 15 ng/100 micrograms total lung RNA which is approximately 30-40% of adult levels. In utero exposure to the synthetic glucocorticoid betamethasone was shown to increase specific 4,4' bis([3H]methylsulfonyl)2,2',5,5'- tetrachlorobiphenyl binding, PCB-BP protein, and PCB-BP mRNA if administered from gestational Day 18 and onward. By Days 21 22, glucocorticoid treatment resulted in a two- to threefold increase in the levels of specific ligand binding, immunoreactivity, and mRNA, i.e., to approximately adult levels. PMID- 1605639 TI - Purification and characterization of dimethylallyl tryptophan synthase from Claviceps purpurea. AB - Dimethylallyl tryptophan synthase (DMAT synthase) catalyzes the alkylation of L tryptophan by dimethylallyl diphosphate to form 4-(gamma,gamma-dimethylallyl)-L tryptophan. The enzyme from mycelia of Claviceps purpurea was purified approximately 125-fold to apparent homogeneity by chromatography on n-butyl Sepharose, Q Sepharose, phenyl Sepharose, and Protein Pak as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Analysis by gel filtration chromatography and SDS-PAGE indicated that DMAT synthase is an alpha 2 dimer with a molecular mass of 105 kDa. The purified enzyme was active in metal free buffer containing EDTA. However, activity was enhanced upon addition of divalent calcium or magnesium ions to the buffer. Values for KM and Vmax were determined in the metal-free EDTA buffer (KMDMAPP, 14 microM; KML-tryptophan, 40 microM; Vmax, 215 nmol min-1 mg-1), 4 mM CaCl2 (KMDMAPP, 8.0 microM; KML tryptophan, 17 microM; Vmax, 504 nmol min-1 mg-1), and 4 mM MgCl2 (KMDMAPP, 8.0 microM; KML-tryptophan, 12 microM; Vmax, 455 nmol min-1 mg-1). The product was isolated and characterized by 1H NMR, uv, and FAB mass spectrometry. PMID- 1605640 TI - Dexamethasone up-regulates mannose receptor activity by increasing mRNA levels. AB - The macrophage mannose receptor is highly susceptible to modulation by a variety of inflammatory and anti-inflammatory agents. Previous studies have demonstrated that mannose receptor activity is dramatically enhanced in rat bone marrow macrophages following treatment with dexamethasone. In the present study we have investigated potential mechanisms that might be involved in this up-regulation. Uptake of ligands by the mannose receptor was increased 2.5-fold in a dose- and time-dependent manner. Maximal stimulation was seen following treatment of macrophages with 0.1-1.0 microgram/ml of dexamethasone for 24-48 h. Dexamethasone treatment increased both the number of cell surface binding sites and total cellular binding activity to 250% of control levels. In addition, total receptor protein as measured by immunoprecipitation was increased 2.5-fold. Neither the maturation rate nor the turnover rate of the protein was altered by dexamethasone treatment. Using an oligonucleotide probe derived from sequence data from the cloned human receptor cDNA, we investigated the effect of dexamethasone on the expression of mannose receptor mRNA. Following incubation with dexamethasone for 12-24 h, the level of mRNA was significantly increased. These results demonstrate that dexamethasone treatment of rat bone marrow macrophages induces synthesis of new receptor protein through an increase in the level of mannose receptor mRNA. PMID- 1605641 TI - Purification and characterization of a catalase-peroxidase from the fungus Septoria tritici. AB - Three classes of heme proteins, commonly designated hydroperoxidases, are involved in the metabolism of hydrogen peroxide: catalases, peroxidases, and catalase-peroxidases. While catalases and peroxidases are widely spread in animals, plants, and microorganisms, catalase-peroxidases were characterized only in prokaryotes. We report here, for the first time, on a catalase-peroxidase in a eukaryotic organism. The enzyme was purified from the fungal wheat pathogen Septoria tritici, and is one of three different hydroperoxidases synthesized by this organism. The S. tritici catalase-peroxidase, designated StCP, is similar to the enzymes previously isolated from the bacteria Rhodobacter capsulatus, Escherichia coli, and Klebsiella pneumoniae, although it is significantly more sensitive to denaturing conditions. In addition to its catalatic activity StCP catalyzes peroxidatic activity with o-dianisidine, diaminobenzidine, pyrogallol, NADH, and NADPH as electron donors. The enzyme is a tetramer with identical subunits of 61,000 Da molecular weight. StCP shows a typical high-spin ferric heme spectrum with a Soret band at 405 nm and a peak at 632 nm, and binding of cyanide causes a shift of the Soret band to 421 nm, the appearance of a peak at 537 nm, and abolition of the peak at 632 nm. Reduction with dithionite results in a decrease in the intensity of the Soret band and its shift to 436 nm, and in the appearance of a peak at 552 nm. The pH optimum is 6-6.5 and 5.4 for the catalatic and peroxidatic activities, respectively. Fifty percent of the apparent maximal activity is reached at 3.4 mM and 0.26 mM for the catalatic and peroxidatic activities, respectively. The enzyme is inactivated by ethanol/chloroform, and is inhibited by KCN and NaN3, but not by the typical catalase inhibitor 3-amino 1,2,4-triazole. PMID- 1605642 TI - Glutathione oxidase activity of selenocystamine: a mechanistic study. AB - Selenocystamine (RSe-SeR) was shown to catalyze the oxygen-mediated oxidation of excess GSH to glutathione disulfide, at neutral pH and ambient PO2. This glutathione oxidase activity required the heterolytic reduction of the diselenide bond, which produced two equivalents of the selenolate derivative selenocysteamine (RSe-), via the transient formation of a selenenylsulfide intermediate (RSe-SG). Formation of RSe- was the only reaction observed in anaerobic conditions. At ambient PO2, the kinetics and stoichiometry of GSSG production as well as that of GSH and oxygen consumptions demonstrated that RSe- performed a three-step reduction of oxygen to water. The first step was a one electron transfer from RSe- to dioxygen, yielding superoxide and a putative selenyl radical RSe., which decayed very rapidly to RSe-SeR. In the second step, RSe- reduced superoxide to hydrogen peroxide through a much faster one-electron transfer, also associated with the decay of RSe. to RSe-SeR. The third step was a two-electron transfer from RSe- to hydrogen peroxide, again much faster than oxygen reduction, which resulted in the production of RSe-SG, presumably via a selenenic acid intermediate (RSeOH) which was trapped by excess GSH. This third step was studied on exogenous hydroperoxide in anaerobic conditions, and it could be eliminated from the glutathione oxidase cycle in the presence of excess catalase. The role of RSe- as a one- and two-electron reductant was confirmed by competitive carboxymethylation with iodoacetate. RSe- was able to rapidly reduce ferric cytochrome c to its ferrous derivative. The overall rate of catalytic glutathione oxidation was GSH concentration dependent and oxygen concentration independent. Excess glutathione reductase and NADPH increased the catalytic oxidation of GSH, probably by switching the rate-limiting step from selenylsulfide to diselenide cleavage. When GSH was substituted for dithiothreitol, it was shown to reduce RSe-SeR to RSe- in a fast and quantitative reaction, and selenocystamine behaved as a dithiothreitol oxidase, whose catalytic cycle was dependent on oxygen concentration. The oxidase cycle of glutathione was inhibited by mercaptosuccinate, while that of dithiothreitol was not affected. When mercaptosuccinate was substituted for GSH, a stable selenenylsulfide was formed. These observations suggest that electrostatic interactions affect the reductive cleavage of diselenide and selenenylsulfide linkages. This study illustrates the ease of one-electron transfers from RSe- to a variety of reducible substrates. Such free radical mechanisms may explain much of the cytotoxicity of alkylselenols, and they demonstrate that selenocystamine is a poor catalytic model of the enzyme glutathione peroxidase. PMID- 1605643 TI - Structural features of the 66-kDa subunit of the energy-transducing NADH ubiquinone oxidoreductase (NDH-1) of Paracoccus denitrificans. AB - The structural gene of the Paracoccus denitrificans NADH-ubiquinone oxidoreductase encoding a homologue of the 75-kDa subunit of bovine complex I (NQO3) has been located and sequenced. It is located approximately 1 kbp downstream of the gene coding for the NADH-binding subunit (NQO1) [Xu, X., Matsuno-Yagi, A., and Yagi, T. (1991) Biochemistry 30, 6422-6428] and is composed of 2019 base pairs and codes for 673 amino acid residues with a calculated molecular weight of 73,159. The M(r) 66,000 polypeptide of the isolated Paracoccus NADH dehydrogenase complex is assigned the NQO3 designation on the basis of N-terminal protein sequence analysis, amino acid analysis, and immuno cross-reactivity. The encoded protein contains a putative tetranuclear iron sulfur cluster (probably cluster N4) and possibly a binuclear iron-sulfur cluster. An unidentified reading frame (URF3) which is composed of 396 base pairs and possibly codes for 132 amino acid residues was found between the NQO1 and NQO3 genes. When partial DNA sequencing of the regions downstream of the NQO3 gene was performed, sequences homologous to the mitochondrial ND-1, ND-5, and ND 2 gene products of bovine complex I were found, suggesting that the gene cluster carrying the Paracoccus NADH dehydrogenase complex contains not only structural genes encoding water-soluble subunits but also structural genes encoding hydrophobic subunits. PMID- 1605644 TI - Characterization and mechanism of (4S)-limonene synthase, a monoterpene cyclase from the glandular trichomes of peppermint (Mentha x piperita). AB - (4S)-Limonene synthase, a monoterpene cyclase isolated from the secretory cells of the glandular trichomes of Mentha x piperita (peppermint), catalyzes the cyclization of geranyl pyrophosphate to (4S)-limonene, a key intermediate in the biosynthesis of p-menthane monoterpenes in Mentha species. The enzyme synthesizes principally (-)-(4S)-limonene (greater than 94% of the total products), plus several other monoterpene olefins. The general properties of (4S)-limonene synthase resemble those of other monoterpene cyclases. The enzyme shows a pH optimum near 6.7, an isoelectric point of 4.35, and requires a divalent metal ion for catalysis, either Mg2+ or Mn2+, with Mn2+ preferred. The Km value measured for geranyl pyrophosphate was 1.8 microM. The activity of (4S)-limonene synthase was inhibited by sodium phosphate, sodium pyrophosphate, and reagents directed against the amino acids cysteine, methionine, and histidine. In the presence of Mn2+, geranyl pyrophosphate protected against cysteine-directed inhibition, suggesting that at least one cysteine residue is located at or near the active site. Experiments with alternate substrates and substrate analogs confirmed many elements of the proposed reaction mechanism, including the binding of geranyl pyrophosphate in the form of a complex with the divalent metal ion, the preliminary isomerization of geranyl pyrophosphate to linalyl pyrophosphate (a bound intermediate capable of cyclization), and the participation of a series of carbocation:pyrophosphate anion pairs in the reaction sequence. PMID- 1605645 TI - Reversible light/dark modulation of spinach leaf nitrate reductase activity involves protein phosphorylation. AB - Spinach (Spinacia oleracea L.) leaf nitrate reductase (NADH:NR;NADH:nitrate oxidoreductase, EC 1.6.6.1) activity was found to rapidly change during light/dark transitions. The most rapid and dramatic changes were found in a form of NR which was sensitive to inhibition by millimolar concentrations of magnesium. This form of NR predominated in leaves in the dark, but was almost completely absent from leaves incubated in the light for only 30 min. When the leaves were returned to darkness, the NR rapidly became sensitive to Mg2+ inhibition. Modulation of the overall reaction involving NADH as electron donor was also found when reduced methyl viologen was the donor (MV:NR), indicating that electron transfer had been blocked, at least in part, at or near the terminal molybdenum cofactor site. Changes in activity appear to be the result of a covalent modification that affects sensitivity of NR to inhibition by magnesium, and our results suggest that protein phosphorylation may be involved. NR was phosphorylated in vivo after feeding excised leaves [32P]Pi. The NR subunit was labeled exclusively on seryl residues in both light and dark. Tryptic peptide mapping indicated three major 32P-labeled phosphopeptide (Pp) fragments. Labeling of two of the P-peptides (designated Pp1 and 3) was generally correlated with NR activity assayed in the presence of Mg2+. In vivo, partial dephosphorylation of these sites (and activation of NR assayed with Mg2+) occurred in response to light or feeding mannose in darkness. The light effect was blocked completely by feeding okadaic acid via the transpiration stream, indicating the involvement of type 1 and/or type 2A protein phosphatases in vivo. While more detailed analysis is required to establish a causal link between the phosphorylation status of NR and sensitivity to Mg2+ inhibition, the current results are highly suggestive of one. Thus, in addition to the molecular genetic mechanisms regulating this key enzyme of nitrate assimilation, NR activity may be controlled in leaves by phosphorylation/dephosphorylation of the enzyme protein resulting from metabolic changes taking place during light/dark transitions. PMID- 1605647 TI - Characteristics of NADPH-dependent thymidylate synthetase purified from Streptomyces aureofaciens. AB - NADPH-dependent thymidylate synthetase from Streptomyces aureofaciens has been purified to homogenity by a two-step chromatographic procedure including anion exchange chromatography and affinity chromatography on methotrexate-Sepharose 4B. The enzyme was purified 1025-fold with a 34% yield. Basic characteristics of the enzyme were determined: molecular weight of the enzyme subunit (28,000), pH and temperature optimum, effect of cations, dependency on reducing agents, Km values for dUMP, mTHF, and NADPH (3.78, 21.1, and 38.9 microM, respectively), and inhibition effect of 5-FdUMP. Binding studies revealed the enzyme mechanism to be ordered sequential: dUMP bound before mTHF. S. aureofaciens thymidylate synthetase exhibits an absolute requirement for NADPH for the enzyme activity--a unique feature not displayed by any of the thymidylate synthetases isolated so far. NADPH is not consumed during enzyme reaction, indicating its regulatory role. The properties of S. aureofaciens thymidylate synthetase show that it is a monofunctional bacterial enzyme. PMID- 1605646 TI - Characterization of a rabbit gene encoding a clofibrate-inducible fatty acid omega-hydroxylase: CYP4A6. AB - CYP4A6 mRNAs are induced in the rabbit liver and kidney following treatment with the antihyperlipidemic drug clofibrate. As a first step toward the elucidation of the mechanism controlling the induction of this and other CYP4A genes by clofibrate and other peroxisome proliferators, we have cloned and characterized the CYP4A6 gene. Genomic DNA containing the first 12 exons encoding CYP4A6 was isolated as three recombinant lambda phage, two of which were overlapping. The sequence of more than 1000 bp of the 5' upstream region as well as of the first 12 exons has been determined. These 12 exons encode all but approximately 80 bp at the 3' terminus of CYP4A6. Intron/exon junctions within the coding region of the gene are conserved relative to the rat CYP4A1 and CYP4A2 genes. Primer extension analysis indicates that transcription is initiated 33 bp upstream of the start codon. The CYP4A6 promoter region, like that of the rat CYP4A1 and CYP4A2 genes, does not contain a consensus TATA box. However, a consensus Sp1 recognition element is apparent at -46 bp upstream of the transcription start site. In addition, a sequence related to one of two regulatory elements that control the induction of the rat acyl-CoA oxidase gene by ciprofibrate is present upstream of the CYP4A6 promoter. PMID- 1605648 TI - The reaction of Aspergillus niger catalase with methyl hydroperoxide. AB - The formation of Compound I from Aspergillus niger catalase and methyl hydroperoxide (CH3OOH) has been investigated kinetically by means of rapid scanning stopped-flow techniques. The spectral changes during the reaction showed distinct isobestic points. The second-order rate constant and the activation energy for the formation of Compound I were 6.4 x 10(3) M-1s-1 and 10.4 kcal.mol 1, respectively. After formation of Compound I, the absorbance at the Soret peak returned slowly to the level of ferric enzyme with a first-order rate constant of 1.7 x 10(-3) s-1. Spectrophotometric titration of the enzyme with CH3OOH indicates that 4 mol of peroxide react with 1 mol of enzyme to form 1 mol of Compound I. The amount of Compound I formed was proportional to the specific activity of the catalase. The irreversible inhibition of catalase by 3-amino 1,2,4-triazole (AT) was observed in the presence of CH3OOH or H2O2. The second order rate constant of the catalase-AT formation in CH3OOH was 3.0 M-1 min-1 at 37 degrees C and pH 6.8 and the pKa value was estimated to be 6.10 from the pH profile of the rate constant of the AT-inhibition. These results indicate that A. niger catalase forms Compound I with the same properties as other catalases and peroxidases, but the velocity of the Compound I formation is lower than that of the others. PMID- 1605649 TI - The slow-refolding step of phosphoglycerate kinase as monitored by pulse proteolysis. AB - The kinetics of refolding of yeast phosphoglycerate kinase were studied by following the variation in circular dichroism at 218 nm, the recovery of enzyme activity, and the susceptibility to proteolysis by trypsin and V8-protease. A very rapid phase followed by a slower one was detected by circular dichroism, which revealed the formation of secondary structures. The slower phase, with a macroscopic rate constant of 0.35 min-1, was also detected by the susceptibility of the enzyme to both proteases. It was shown that cleavage sites located in the hinge region, in a part of the C-domain and, to a lesser extent, in a region of the N-domain, which are accessible in the intermediate state, became inaccessible during the slow-refolding step of the molecule. These results demonstrate, on the one hand, the role of domains as folding intermediates, and, on the other hand, the locking of the domain structure and the domain pairing that occurs during the slow-refolding step with a rate constant of 0.35 min-1. The return of the enzyme activity occurred in a slower last step upon conformational readjustments induced by domain interactions. PMID- 1605650 TI - [Evantail resection]. AB - Thirty five of out 87 small breast cancer clinically sized 1.0 cm or less in diameter had invasion in surrounding breast tissue beyond 2.0 cm distant from a border of the tumor on histopathological examination: Seven out of twenty four (29 percent) for the defined type, twenty-one out of forty-eight (44 percent) for the poorly defined type, seven of fifty (47 percent) for the intraductal type of breast cancer. Those results lead me to design "Evantail resection" which was a modification of the quadrantectomy a case out of forty-two patients who underwent Eventail resection had a local recurrence at median follow-up time of 22 months ranging 3 months to 68 months. A technique of the Evantail resection was explained in detail in this articles. PMID- 1605651 TI - [Radiotherapy in the conservative management of breast cancer]. AB - Breast conserving therapy is now considered standard treatment in patients with early breast cancer, and it yields equal local control and survival equal to those of radical mastectomy, in Europe and the United States. After many reports from western countries, Japanese surgeons started conservative treatment for early breast cancer. The aim of radiotherapy is to eradicate residual tumor after quadrantectomy or lumpectomy. Indication for this management by Fujio Kasumi at the Cancer Institute Hospital is T1, N0, M0. We reported here the method of radiotherapy, that is energy of photon, treatment field and total dose, which are discussed by the study group of the Japanese Society for Therapeutic Radiology and Oncology. PMID- 1605652 TI - [Chemotherapy of advanced breast cancer]. AB - The frontline chemotherapy for advanced breast cancer has been either CMF or CAF and the combinations can obtain an overall response rate exceeding 50%, including complete responses of 10-15% and median survival times of 12-18 months. Complete responders have survived longer than patients with partial responses or stable diseases. Consequently, high dose chemotherapy with autologous bone marrow transplantation has been investigated in order to obtain more complete responses and ultimately to obtain a cure in patients responding to induction chemotherapy. Seventeen to 30% of patients who became complete responses have maintained continuously complete responders. Taxol and CI941 are promising agents under investigation. PMID- 1605653 TI - [Adjuvant chemotherapy therapy of breast cancer]. AB - Six to 12 cycles of CMF is regarded as the standard regimen for adjuvant chemotherapy for breast cancer, producing 10-20% increase in survival for premenopausal and node-positive patients. Tamoxifen combined with CMF has induced an additional reduction in recurrence rate only in postmenopausal patients. Oral administration of 5-FU or its derivatives combined with tamoxifen for as long as 1-2 years is the regimen most widely used in Japan for considerable improvement in survival. But it needs further evaluation in comparison with CMF, and in ultimate duration of treatment and better combination with other drugs. Adjuvant chemotherapy for node-negative patients is advocated in the U.S., where the recurrence rate is as high as 30%. Only 10% of Japanese n0 patients undergo recurrence. Therefore, adjuvant therapy should be given only to high-risk patients. PMID- 1605655 TI - [A pharmacokinetic study of idarubicin hydrochloride, a new anthracycline anti tumor drug, in patients with acute leukemia. Idarubicin Study Group]. AB - In 21 patients with acute leukemia, idarubicin hydrochloride, a new anthracycline antitumor drug, was administered i.v. for 3 consecutive days to study the pharmacokinetics. The terminal half-lives (t1/2) of the drug in these patients were 6.40-15.10 hrs. in plasma, and 8.09-16.34 hrs. in blood cells. Its main metabolite idarubicinol remained longer in blood; t1/2 values were 43.46-51.01 hrs. in plasma and 36.61-54.70 hrs. in blood cells. After 2-4 hrs, the concentrations of idarubicinol in both plasma and blood cells exceeded those of idarubicin. The AUCs of idarubicinol in plasma were 5.16-8.36 times higher than those of idarubicin, and AUCs of idarubicinol in blood cells were 2.05-4.57 times higher than those of idarubicin. Among the doses ranged from 5 to 15 mg/m2/day, the AUCs of both idarubicin and idarubicinol increased dose-dependently. In 2 compartment multiple dose models, plasma t1/2 alpha and t1/2 beta of idarubicin were 0.25 +/- 0.13 hrs. and 9.4 +/- 3.4 hrs., respectively. The steady-state volume of distribution (Vdss) was 934.9 +/- 370.7 l/m2, and the plasma clearance was 82.3 +/- 29.7 l/hr/m2. The urinary excretion of the drug was comparatively low. Until 7 days after administration, the mean cumulative urinary recovery rates of idarubicin and idarubicinol were 2.04% and 11.53%, respectively, and 13.57% in total. PMID- 1605656 TI - [Antitumor effect of carboplatin on in vitro three-dimensional tumor]. AB - We studied the antitumor effect of Carboplatin on the three-dimensional tumor in vitro. First, we observed the three-dimensional growth of cultured tumor cell lines (Hep 2, KB and HT 29 cells), which were developed in the combined culture system of fibrin matrix and agar culture. The tumor cells developed a 3 x 3 mm tumor in diameter in the in vitro 10 day-culture system. This size was large enough to allow the histologic study. When we applied Carboplatin to the three dimensional tumors, histologic change of the three-dimensional tumor developed from Hep 2 and KB cells were observed in a dose dependent manner. However, no remarkable histologic change was observed in the three-dimensional tumor developed from HT 29 cells. These results suggest the experimental system of three-dimensional tumor can predict histologically the antitumor effect of Carboplatin on various tumors at the solid tumor level. PMID- 1605654 TI - [Recent progress of endocrine therapy in breast cancer]. AB - Recent progresses of endocrine therapy for advanced and early breast cancer was reviewed. The mechanism (s) of an antiestrogen, tamoxifen has been noted at least partly as a stimulation of TGF beta action in ER-positive breast cancer cells. The Early Breast Cancer Trialists' Collaborative Group (EBC TCG) has recently reported the effectiveness of endocrine therapy, oophorectomy for premenopausal patients, and tamoxifen for pre- and post-menopausal patients in the adjuvant treatment for operable breast cancer patients. Two kinds of newly developed endocrine therapy were mentioned; LH-RH analogues for premenopausal patients, and aromatase inhibitors for postmenopausal patients. These agents decrease the plasma estrogen levels, acting like the ablative surgery, and make us more comprehensive combinations of endocrine therapy of breast cancer. PMID- 1605657 TI - [Effects of anthracycline drugs (aclarubicin, daunorubicin, doxorubicin, epirubicin, pirarubicin) on mouse acute toxicity and rat liver microsomal lipid peroxidation]. AB - Effects of anthracycline type antitumor agents (aclarubicin, ACL; daunorubicin, DAU; doxorubicin, DOX; epirubicin, EPI; pirarubicin, PIR) on the acute toxicity to mouse, rat liver microsomal lipid peroxidation and mitochondrial functions in vitro were studied. ACL showed the least production of liver microsomal lipid peroxidation in all tested anthracyclines in the increasing order of PIR, DOX, DAU and EPI. The increase of production of lipid peroxidation induced by these drugs correlated well with the decrease in body weight of mice administered i.p. at 20 mg/kg and 50% lethal dose of these drugs. On the effect of mitochondrial function, all drugs tested decreased the oxygen uptake of state 3 and the level of respiratory control index. ACL showed the most severe inhibition of these functions in all drugs. These observations suggest that the degree of microsomal lipid peroxidation induced with the anthracycline drugs was related to the development of the drug acute toxicity. PMID- 1605659 TI - [Prevention of stomatitis in patients with acute myelogenous leukemia using PVP iodine (Isodine) gargle]. AB - From November 1987 to October 1990, we investigated the efficacy of povidine iodine gargle solution (Isodine Gargle) for preventing stomatitis in 26 patients (19 males and 7 females; mean age 53.2 years) with acute myelogenous leukemia (AML). The patients were given a concentrated preparation of the gargle solution which they had to dilute 50 times, and were asked to use it 8 times/day for one year. Twenty patients (76.9%) frequently suffered from stomatitis despite the gargling. Therefore, in the second year they were instructed to use the gargle solution at a higher concentration (30-fold dilution). On the third year, they were asked to increase the frequency of gargling to 10 times/day; this resulted in a significant decrease in frequency of the episodes of stomatitis. Severe and painful stomatitis no longer occurred. Gargling with povidine iodine gargle solution was thus considered effective for preventing stomatitis in AML patients. PMID- 1605658 TI - [Strategy for therapy of malignant ascites using MTT assay]. AB - Since the prognosis of patients with malignant ascites is generally poor, the establishment of a therapeutic plan should be done as soon as possible. In order to select the most suitable antitumor agent, a drug-sensitivity test was done by MTT assay using fresh autologous tumor cells as targets. Autologous tumor cells were collected from their ascitic fluids. Results obtained here indicate a possible strategy for the treatment of patients with malignant ascites by MTT assay. PMID- 1605660 TI - [A comparison of nystatin with norfloxacin for prevention of infection after consolidation therapy in patients with acute leukemia or autologous bone marrow transplantation: a randomized study]. AB - Seventy-three patients mainly receiving consolidation therapy for acute leukemia or autologous bone marrow transplantation were studied in a randomized trial comparing nystatin with norfloxacin (800 mg) given orally QID, for prevention of infection. Both groups were equally distributed in regard to age, disease, and duration of granulocytopenia, although far more patients entered the laminar air flow room in the norfloxacin group. Duration of more than a 39 degrees C fever was much longer in the nystatin group than in the norfloxacin group: Bacteremia, microbiologically documented infections, and fever of unknown origin were more frequently seen in the nystatin group, but there was no significant difference between the two groups. On the other hand, patients without fever during granulocytopenia were more numerous in the norfloxacin group than in the nystatin group (p less than 0.05). Furthermore, three deaths during granulocytopenia occurred in the nystatin group. In conclusion, prophylactic administration of norfloxacin during granulocytopenia showed a significant afebrile period. PMID- 1605662 TI - [BH-AC.nitrosourea-therapy for refractory or relapsed malignant lymphoma]. AB - Thirty patients with refractory or relapsed non-Hodgkin's lymphoma were treated with behenoyl ara-C (BH-AC) and nitrosoureas. Sixteen patients (53%) had a diffuse, large cell lymphoma and 22 patients (73%) had a stage IV disease. BH-AC, 250 mg/body, in combination with ACNU or MCNU, 50 mg/body, was administered by drip infusion for two days (Day 1, 2) every 3 to 4 weeks. Six patients (20%), all of them relapsed cases of diffuse lymphoma, obtained complete remission lasting one to six (mean: 2.5) months and 15 patients (50%) obtained partial remission lasting one to five (mean: 2.7) months. The major side effect was thrombocytopenia, and nine patients (30%) had required platelet-transfusions. There was no case complicated by infection due to prolonged neutropenia. Therefore, we conclude that BH-AC.Nitrosourea-therapy is very useful for the salvage chemotherapy of malignant lymphoma. PMID- 1605661 TI - [A study of preclinical and clinical usefulness of new tumor markers of ovarian carcinoma, CA 54/61 and CA 602. 1. Evaluation of the diagnostic accuracy of CA 54/61, a study of the normal range of its values and its correlation with other tumor markers]. AB - We made a preclinical study of CA 54/61, a recently developed marker of ovarian tumors, and also conducted a clinical study of it using serum samples collected from 58 institutions located throughout Japan. This paper describes the results of the preclinical study of the CA 54/61 marker that were obtained with a kit based on an enzyme immunoassay (EIA), and also the findings with the kit in the clinical study pertaining to the normal range of its values, its values relative to age, menstrual cycle, and pregnancy, and its correlations with other tumor markers. The tests for reproducibility of assay results, the analytical recovery test, and the dilution test all gave favorable results: the marker proved reliable in both precision and reproducibility. Two cut-off values were used: the mean + 2 S.D. of the mean for healthy subjects, or 20 U/ml; and the value for the maximum diagnostic efficacy, i.e., 12 U/ml. The assay results did not vary greatly with either age, menstrual cycle or pregnancy stage, which suggested that CA 54/61 might be a marker less liable to be affected by physiological conditions prevailing at the time of sample collection. The result correlated poorly with those of assays with other markers; thus CA 54/61 proved to differ in property from the previously recognized tumor markers. PMID- 1605663 TI - [Phase I study of a new platinum complex 254-S, cis-diammine (glycolato)-platinum (II)]. AB - A new platinum complex 254-S had a superior preclinical therapeutic indices compared to cisplatin, showing decreased renal and gastrointestinal toxicities. Phase I clinical study with a single dose schedule was conducted to investigate the safety, toxicity, pharmacokinetics and possible efficacy against various advanced cancers by a cooperative study of 10 institutions. The drug was administered by i.v. infusion for 60 min dissolved in 250 ml of 5% xylitol solution, without the use of hydration and antiemetics. At least 3 patients at each dose level of 10, 20, 40, 80, 100 and 120 mg/m2 were tested and 28 patients were entered into this study. Myelosuppression, especially thrombocytopenia, appeared strongly at dose level of 80 mg/m2 and dose limiting thrombocytopenia was found in 2 of 5 patients. Leukocytopenia was also dose-related but moderate. Platelet and WBC nadirs occurred around 3 weeks after administration with recovery in about one week. Although slight elevation of BUN and creatinine were temporarily observed in a few cases, no significant renal toxicity was observed. Anorexia, nausea and vomiting were observed in the majority of patients, but milder than cisplatin. In conclusion, 254-S has demonstrated reduced non hematologic toxicities as compared to cisplatin. This drug appears to be well tolerated and 120 mg/m2 was maximum tolerated dose. The recommended dose for phase II studies was thought to be 100 mg/m2 by i.v. infusion every 4 weeks. PMID- 1605664 TI - [An early phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers]. AB - An early phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 10 institutions. Based on the results obtained in the phase I study, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion after being dissolved in 300 ml of 5% xylitol. In principle, the 254-S administration was repeated at least 2 times at 4 week intervals. Hydration was performed, if needed. All 24 cases registered were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 4 patients (16.7%), partial response (PR) in 5 (20.8%), no change (NC) in 11 and progressive disease (PD) in 4, for a 37.5% response rate. Three CR and 3 PR (40.0%) were obtained in 15 patients with prior chemotherapy, including 1 CR and 2 PR (33.3%) in 9 patients previously treated with cisplatin. Side effects were observed in 19 patients (79.2%). Major toxic effects were hematotoxicity, including thrombocytopenia (58.3%), leukopenia (58.3%) and anemia (33.3%), and gastrointestinal toxicity, including nausea and vomiting (45.8%) and anorexia (37.5%). Abnormal parameter changes on renal function were found in 2 patients (8.3%). Based on these results, it was concluded that 254-S is potentially a useful anticancer agent for the treatment of head and neck cancer, and should be further investigated in a late phase II clinical study. PMID- 1605665 TI - [A late phase II clinical study of cis-diammine glycolato platinum, 254-S, for head and neck cancers]. AB - A late phase II clinical study of 254-S, a new anticancer platinum complex, for head and neck cancer was conducted by the 254-S Head and Neck Cancer Study Group consisting of 31 institutions. As in the early phase II study for head and neck cancers, 254-S was administered at 100 mg/m2 by 60 min intravenous drip infusion, repeated at least twice at 4-week intervals. Of 80 cases registered, 66 were regarded as complete cases evaluable for tumor response. Complete response (CR) was observed in 7 patients (10.6%), partial response (PR) in 22 (33.3%), no change (NC) in 24 and progressive disease (PD) in 13, for a 43.9% response rate. Two CR and 11 PR (37.1% response rate) were obtained in 35 patients with prior chemotherapy, including 2 CR and 7 PR (33.3% response rate) in 27 patients previously treated with cisplatin. Of 70 patients evaluable for toxicity, side effects were observed in 60 patients (85.7%). Major toxic effects were hematotoxicity, including leukopenia (62.9%), thrombocytopenia (40.0%) and anemia (45.7%), gastrointestinal toxicity, including nausea and vomiting (64.3%), and anorexia (47.1%); grade 3 or 4 thrombocytopenia was found in 20.0% of the patients, and this toxicity was regarded as the dose limiting factor. Nephrotoxicity observed was mild and infrequent. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of head and neck cancer. PMID- 1605666 TI - [A phase II clinical study of cis-diammine glycolato platinum, 254-S, for cervical cancer of the uterus]. AB - A phase II clinical study of 254-S, a new anticancer platinum complex, for cervical cancer was conducted by the 254-S Cervical Cancer Study Group consisting of 10 institutions. 254-S was administered at 80 mg/m2 by intravenous drip infusion and this administration was repeated at least 2 times at 4-week intervals, in principle. Forty of 45 patients registered, were eligible and 38 were evaluable for tumor response (complete cases). Complete response (CR) and partial response (PR) were obtained in 4 (10.5%) and 9 patients (23.7%), respectively, for a 34.2% response rate. Against squamous cell carcinoma, a 38.2% response rate (4 CR and 9 PR in 34 patients) was obtained. The response rate obtained in patients with no prior chemotherapy was 40.0% (2 CR and 8 PR in 25 patients), while that in patients with prior chemotherapy was 23.1% (2 CR and 1 PR in 13 patients). Major toxic effects observed were hematotoxicity, including thrombocytopenia (35.1%), leukopenia (73.0%), anemia (75.7%), gastrointestinal toxicity such as nausea and vomiting (83.8%) and anorexia (83.8%). Nephrotoxicity observed was in the form of an elevation of serum creatinine with an incidence of 2.7% and a decrease in creatinine clearance with an incidence of 21.7%. In comparison with the results obtained in the phase II clinical study for gynecological cancers in which 254-S was administered at 100 mg/m2, the response rate obtained in this study was slightly lower but thrombocytopenia and leukopenia observed were less frequent and milder. Based on these results, it was concluded that 254-S is a very useful anticancer agent for the treatment of cervical cancer. PMID- 1605667 TI - [Mitomycin-C-sensitive carcinoid tumor of the gallbladder: report of a case]. AB - A case of carcinoid tumor of the gallbladder, which was sensitive to mitomycin-C is reported. A 49-year-old male was admitted to our hospital with a 2-month history of epigastralgia. He underwent right extended lobectomy of the liver, pancreaticoduodenectomy and lymph node dissection. Histology revealed a carcinoid tumor of the gallbladder with invasion of the liver and lymph node metastasis. About 2 months after the operation, right supraclavicular lymph node metastasis was detected and CT scan revealed abdominal paraaortic lymph node metastasis. The patient was given cis-platinum, but the right supraclavicular lymph node metastasis increased in size and number. After administration of mitomycin-C, the paraaortic lymph node metastasis disappeared. Carcinoid tumor obtained from the right supraclavicular lesion was inoculated into BALB/c nude mice, and sensitivity to anticancer drugs was assayed. This carcinoid tumor was sensitive to mitomycin-C but not to cisplatinum, adriamycin, or nimustine. PMID- 1605668 TI - [A case of gallbladder cancer with marked response to EAP treatment]. AB - A case of unresectable gall bladder cancer due to multiple metastasis was dealt with EAP (VP-16, ADM, CDDP) treatment. The case was a 49-year-old male who was admitted to the hospital with a 3 cm sized umbilical tumor. After 2 cycles of the treatment, the tumor size significantly decreased and the symptoms diminished. In parallel, the symptoms from bone metastasis and dissemination also disappeared. As for tumor markers, CA 19-9 indicated 5151 U/ml, fell down to the normal range after the treatment. In this case, the efficacy of EAP treatment to the primary gall bladder carcinoma was undetectable, because of the difficulty of elucidation of the primary site by diagnostic images. However, all data suggested that EAP treatment was effective to the advanced unresectable gallbladder cancer, at least to its metastatic sites. PMID- 1605669 TI - [A case of pulmonary metastasis of ovarian leiomyosarcoma responsive to CTP therapy]. AB - One case of pulmonary metastasis of leiomyosarcoma responsive to CTP therapy was reported. The patient was a 44-year-old woman who had undergone total simple hysterectomy for uterine myoma 6 years before. Five years after the operation she underwent ovariectomy for ovarian tumor. Based on the histopathological findings, she was diagnosed to have leiomyosarcoma. One year later the patient was referred to use because of pulmonary metastasis. After admission to our hospital CTP therapy was started. Disappearance of the metastatic lesion was demonstrated by the chest X-ray findings at the end of five courses of treatment. PMID- 1605670 TI - [Portal blood levels of mitomycin C after intraperitoneal administration]. PMID- 1605672 TI - [Cell culture and its application. Culture systems of normal human epithelial cells and their potential applications in cancer research]. AB - In cancer research, it is essential to understand the differences of normal and carcinoma cells. To date there are not many studies of normal human epithelial cells because of difficulties in obtaining human materials and culturing them. After Peehl and Ham developed a low calcium medium which does not require feeder cells, the culture of normal human epithelial cells became relatively easy. In this paper, I will describe and compare different culture methods for normal human epithelial cells (mainly keratinocyte culture systems). We also present establishment processes of normal human ectocervical epithelial cell culture system that is dramatically improved by a combination of serum supplemented high calcium and serum-free low-calcium media according to changes of a physiological state of the cells by passages. This suggest that we have to be aware of changes of cells in responses and use them in developing culture systems. I will also describe a study of mouse epidermal keratinocyte culture system and discuss the use of normal human epithelial cell system in screening potential chemotherapy reagents. In the study normal epithelial cells inhibit growth of initiated cells and this inhibition can be modified by tumor promoters and their inhibitors. PMID- 1605671 TI - [Combination chemotherapy with mitoxantrone, etoposide, vindesine and prednisolone for relapsed or refractory malignant lymphoma: presence of cross resistance to CHOP therapy]. PMID- 1605673 TI - Markers for endothelial injury, clotting and platelet activation in preeclampsia. AB - The etiology of disseminated intravascular coagulation (DIC) in preeclampsia is not well understood. We measured plasma levels of fibronectin (FN), which may reflect endothelial cell injury, fibrinopeptide A (FPA), a specific marker of clotting, platelet counts (PLC) and mean platelet volumes (MPV), as well as beta thromboglobulin (beta TG) and platelet factor 4 (Pf4), products of irreversible platelet activation in 24 preeclamptic patients and 24 controls matched for age, gestational age, labor status, and parity. In preeclampsia, FN and FPA were significantly elevated while PLC were significantly decreased (P less than 0.0001, less than 0.05 and less than 0.01, respectively). beta TG, Pf4, and MPV values did not show significant differences. These findings support the hypothesis that endothelial injury, clotting activation and platelet consumption are increased in preeclampsia. However, the much closer association of preeclampsia with FN levels as compared to FPA, beta TG, Pf4, suggests that endothelial injury is a more basic mechanism of preeclampsia than clotting or platelet activation. PMID- 1605674 TI - Incidence of glove perforation during episiotomy repair. AB - A total of 416 gloves were tested for punctures after 200 episiotomy repairs. Evidence of perforation was found in 34 (8%) of the gloves used and in only half the cases did the surgeon actually realise that a perforation had occurred. The left index finger and thumb were more often perforated than other parts of the gloves. The implications of the findings, especially as regards spread of infections to surgeons, are discussed. PMID- 1605675 TI - Effects of protracted administration of estriol on the lower genito urinary tract in postmenopausal women. AB - We investigated 80 postmenopausal women, 48 of whom (60%) agreed to undergo long term treatment with estriol suppositories. All had symptoms of vaginal atrophy and urinary incontinence. Endometrial samples were taken after 8-10 years of therapy. Estriol had induced slight proliferative changes in the endometrium in 7 of 48 patients studied by endometrial sampling. 75% of the women reported significant subjective improvement of stress incontinence. Estriol supplementation did not produce any significant change in urethral pressure, functional length, or cystometric parameters. However, a significant increase in pressure transmission ratio to the proximal urethra was noted after vaginal medication with estriol. Replacement therapy in post-menopausal women must take into account the patients perception of risks and benefits. The risk of estriol treatment is insignificant. PMID- 1605677 TI - Hormonal regulation of endometriotic cell growth in primary cell culture system. AB - A primary cell culture of endometriotic cells was established to examine the hormonal regulation of endometriosis. The addition of estradiol had no effect on the DNA synthesis of cultured endometriotic cells. Progesterone at 10(-7) M caused a significant reduction in the amount of the DNA synthesis. An inhibitory effect of progesterone was completely eliminated by the concomitant addition of RU486, an antiprogesterone. The addition of epidermal growth factor (EGF) at 1 ng/ml significantly increased the DNA synthesis. Other growth factors, such as fibroblast growth factor and insulin-like growth factor also produced a modest but significant increase in DNA synthesis. These results seem to provide clues for clarifying the pathophysiology of endometriosis. PMID- 1605676 TI - Do chemo- and radiotherapy affect the DNA repair ability of lymphocytes? AB - The DNA repair ability of unstimulated lymphocytes damaged by ultraviolet irradiation was measured in a group of 15 breast cancer patients before surgery, and 3 to 5 years later a) after surgery alone (n = 6), or b) after surgery with additional chemo- and/or radiotherapy (n = 9). In group a) 3 out of 6 patients had reduced repair before and 2 out of 6 after surgery. In the group b) 4 out of 9 patients had reduced repair before surgery, and 9 out of 9 after surgery plus chemo/radiotherapy. These results confirm our previous finding that chemo/radiotherapy influences DNA repair negatively. Because of the known association between reduced DNA repair and cancer occurrence, this could increase the risk of a secondary tumour. PMID- 1605678 TI - Numerical chromosome anomalies after fertilization of freeze-thawed mouse oocytes. AB - The chromosome complement of first cleavage stage mouse embryos was analyzed to investigate the effect of slow freezing-fast thawing cryopreservation on chromosome numbers by comparing these numbers with those found fresh after fertilization of control oocytes. Fewer frozen-thawed (34.1%) than control oocytes (75.0%) cleaved to the 2-cell stage after in vitro fertilization. The incidence of hyperploidy was significantly increased by freezing (4.5% vs. 0% in controls). Polyploidy was not significantly affected (17.0% for freeze-thaw embryos vs. 26.2% for controls). PMID- 1605679 TI - Rapid determination of fetal sex using amniotic fluid cells and the polymerase chain reaction. AB - We determined the sex of 50 fetuses by an amplification of the Y-chromosome specific fragment using the polymerase chain reaction (PCR). Amniotic fluid cells were collected by amniocentesis from pregnant women at 14 to 17 weeks of gestation. Total DNA was purified from cells in 1 ml of amniotic fluid. When only the expected 130 base pair X-chromosome specific fragment was detected, we identified the fetus as female, while when both the expected 170 base pair Y chromosome specific and X-chromosome specific fragments were detected, we identified it as male. In all cases, identification was confirmed either by chromosome analysis or post partum. PMID- 1605680 TI - Lethal Pena-Shokeir 1 syndrome in three male siblings. AB - A consanguineous family with no living children and three male siblings with Pena Shokeir 1 syndrome is described. Two children died antepartum and the third shortly after delivery. The importance of early prenatal diagnosis, appropriate counseling and thorough evaluation of the neuromuscular system is discussed. PMID- 1605681 TI - [The Francisco Diaz Medal: Puigvert's idea]. PMID- 1605682 TI - [The recording of renal cortical blood flow by laser Doppler flowmetry]. AB - Several techniques are available for measuring the microcirculation. The results, however, cannot be extrapolated due to the different, intricate microvasculature of each organ system. We measured the renal cortical blood flow using laser Doppler flowmetry. This flowmeter permits blood flow measurements of very small areas of tissue. Precise information from selected areas, such as the renal cortex, can thus be obtained. The results are expressed in perfusion units (PU). PMID- 1605683 TI - [A Foley-type catheter with a steerable tip]. AB - Permanent bladder catheterization for medical or social reasons increases the risk of complications, especially urinary infection. We evaluated the usefulness of the balloon catheter with a steerable intravesical tip in reducing the volume of residual urine between the bladder neck and the balloon of the conventional Foley catheter. The results show that this new catheter affords no additional advantage over the conventional catheter. PMID- 1605684 TI - [Kidney injuries: a review of 149 cases. A change in the diagnostic and therapeutic approaches]. AB - We reviewed 149 cases of renal trauma that were seen at the Urology Service of Hospital de Navarra from January, 1975 to December, 1989. The severity of the renal injury, type (open or closed), the presence of previous lesions, renal changes, and the diagnostic and therapeutic approaches were analyzed. The follow up urologic and nephrologic controls are briefly described. Most of the cases with important renal injury have been followed for one to five years. We observed as increased incidence of renal injuries from road traffic accidents in younger patients with a prevalence in the male. Treatment is more conservative and less nephrectomies have been performed. CT, US, renal arteriography and isotope studies have become widely available. The endourological and transcutaneous techniques have been widely used in the treatment of these patients. PMID- 1605685 TI - [The anterior approach after Chute, Baron and Olsson in renal pathology: the authors' own experience]. AB - The authors describe their experience of 79 operations using the Chevron anterior transperitoneal approach in the treatment of 71 renal tumors and 8 cases of renal trauma. This approach respects the physiology of the respiratory system, has a low morbidity and mortality, in the post-operative period the need for anesthesia is moderate and hospitalization is shorter. The authors underscore the following advantages of the Chute-Baron-Olsson technique: it is easy to perform and can be easily extended, dehiscence and laparoceles are uncommon (only 2 of 79 patients). Furthermore, the Chevron partial or total approach in tumors and renal trauma permits exposure of an excellent inframesocolic and supramesocolic field and perfect control of the important elements of the renal vasculature. PMID- 1605687 TI - [The imaging diagnosis of adrenal tumors]. AB - From 1967 to 1991 we have diagnosed and treated 73 adrenal tumors in 63 patients: 12 pheochromocytomas, 24 adrenal cortical adenomas, 15 hyperplasias, 16 carcinomas, 3 myelolipomas, 2 cysts and 1 neuroblastoma. We conducted a retrospective study to analyze the preoperative images obtained by different diagnostic techniques and attempted to correlate tumor size and site with the results of the histological analysis of the surgical specimen. Nephrotomography with pneumoretroperitoneum and IV Nephrotomography were useful in detecting the increase of the size of the gland in 10 of 25 cases submitted to these procedures (40%). Arteriography as second or third technique of choice confirmed the presence of an adrenal tumor in 15 of the 21 cases evaluated by this procedure (70%). US and CT detected 94% (31/33) and 100% (33/33) of the cases, respectively. Fourteen cases were incidentally discovered by CT (7) and US (7). A direct relationship between tumor size and degree of malignancy could be established since the carcinomas had a mean diameter of 7 cm (range 5 to 12 cm). Concerning the histologic nature of the disease, specific images were found in 3 cases of adrenal myelolipoma (hyperechoic on US and of low density similar to fat on CT) and 2 cysts (anechoic with posterior band evidenced on us and liquid on CT). Radioisotopes were also utilized for tumor localization and there was positive uptake of I-131-IMBG in 2 cases of adrenal pheochromocytoma; 1 extra adrenal (left lateral aortic paraganglioma) and 1 case of malignant adrenal pheochromocytoma with metastasis to the lungs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605686 TI - [Urological surgery in the octogenarian: excessive preconceptions?]. AB - We reviewed the records of 277 patients aged 80 or older that had been considered for surgery during the period 1980-1990. We analyzed the surgical risk (Goldman and ASA score), patient history, type of surgery and the post-operative course (Karnofsky index) in order to identify the risk factors and to permit objective and practical selection of patients amenable to surgical treatment. Overall, regardless of sex, the benign (35%) and malignant (18%) diseases of the prostate and bladder neoplasms (30%) accounted for more than 80% of the surgical procedures. The early postoperative complications were shown to be influenced by the type of surgery (emergency surgery), the approach (open surgery), the presence of preoperative urinary tract infections and the ASA score. Regardless of the cure rate, the analysis of the postoperative course and data gleaned from telephone interviews indicate that 61.5% of the patients probably had a very good or good quality of life at 6 months. In the non-operated group 1 out of 10 procedures that had been anticipated was not performed and many had a malignant disease. Although there were more patients with fair/poor quality of life in the patient group that did not undergo surgery than in the operated group (42.8% versus 28.5%, respectively), patient general condition at 6 months was very good or good in 50% of the patients that were followed or interviewed. The use of the preoperative evaluation methods and our clinical experience can eliminate subjective evaluation and permit developing safe and precise surgical programs. PMID- 1605688 TI - [Cutaneous and gynecologic metastases disclosing renal-cell carcinoma: the diagnostic and therapeutic implications]. AB - The spread of is uncommon renal cell carcinoma to the female genital system it is even more uncommon to observe metastasis or its symptoms or signs, masking or preceding the clinical manifestations of the primary lesion. In the course of nephrectomy due to renal tumor, the early ligation of the gonadal vein during the control maneuvers of the vascular pedicle can reduce the risk of posterior genital metastasis. Similarly, the skin is an uncommon site of metastasis. The appearance of cutaneous metastasis from renal cell carcinoma may precede the detection of the underlying tumor, although most of the cutaneous metastases are observed after the primary lesion has been detected. In patients with solitary skin metastasis and no evidence of spread to other organ systems, nephrectomy and excision of the metastatic lesion have permitted a survival of 35% at 5 years. PMID- 1605689 TI - [Transvesical ureteroneocystostomy: the assessment of vesicoureteral reflux in the kidney transplant]. AB - In 51 heterotopic renal transplants performed in our setting, the continuity of the urinary tract was achieved by transvesical ureteroneocystostomy utilizing the Politano-Leadbetter and Paquin techniques. A retrospective study was conducted to determine the incidence of vesicoureteral reflux (VUR) in patients submitted to the foregoing techniques. Reflux was observed in only 1 (2.32%) of the 43 patients who were evaluated by voiding cystography. Urinary tract infection (UTI) was observed in 27 patients (62.7%). Of these, 5 (18.5%) had acute pyelonephritis. Most of the patients with no evidence of vesicoureteric reflux presented urinary tract infection (96.3%). The transvesical techniques achieved a low reflux rate. No difference was observed relative to the incidence of reflux for one or the other technique. No relationship could be established between VUR and UTI. Evaluation is warranted in patients with recurrent UTI that is refractory to antibiotic therapy or deterioration of renal function that cannot be ascribed to other causes. PMID- 1605690 TI - [Pyeloureteral stenosis: its treatment by endopyelotomy]. AB - Percutaneous endopyelotomy is becoming widely accepted in the treatment of primary or secondary stenosis of the ureteropelvic junction because it achieves excellent results and is less invasive. Herein we describe our experience with this technique, which we perform with the electric knife and large caliber ureteral stents. Seventeen endopyelotomy procedures were performed in 16 patients with a minimum follow-up of one year. This technique successfully resolved the stenosis in 14 cases. We consider it to be the procedure of choice due to the excellent results and the low complication rate. PMID- 1605691 TI - [The endourological treatment of distal ureteral fistulae in the kidney transplant. The exclusion or "dry" technic]. AB - The present study reports our experience in the endourological treatment of fistulas of the distal ureter in renal transplant patients. The temporary urinary exclusion or dry technique was effective in 8 of the 10 patients. We advocate the use of this simple and safe technique which achieves excellent results. PMID- 1605692 TI - [Cystic pyeloureteritis. Our approach]. AB - We report a case of massive cystic pyeloureteritis that had been diagnosed by ureterorenoscopy in a patient with recurrent urinary infection and episodes of nephritic colic. The reports published in the literature indicate there is no specific treatment for this disease whose etiology is unknown. Its pathogenesis has not been well-established and it is difficult to distinguish from other urothelial filling defects. Although it has also been reported that it may progress to malignancy, we believe that the therapeutic approach should be conservative. PMID- 1605693 TI - [A late lymphocele in a kidney transplant]. AB - We report a case of peritransplant lymphocele that developed 11 years after the patient received the first renal graft. Initially, treatment was by percutaneous punction-aspiration and povidone-iodine sclerosis. The important (congruent to 3 liters/day) persistent fluid collection prompted us to resort to surgery (marsupialization) which achieved good results. PMID- 1605694 TI - [Secondary ureterectomy in an ectopic ureteral opening into the seminal vesicle]. AB - The ectopic ureter opening to the seminal vesicle is uncommon in the male and even less in a duplex kidney. It commonly presents as recurrent urinary infection with pelviperineal pain. Treatment is by heminephrectomy with total ureterectomy and removal of the seminal vesicle if it is cystic. Herein we describe a 70-year old patient who had previously undergone a heminephrectomy and partial ureterectomy due to an ectopic ureter opening to the seminal vesicle of the ureter of the upper pelvis of the left kidney. The patient was submitted to a second ureterectomy procedure due to pyoureter in the ureteral stump. The main features of this pathological condition are described and the surgical approach is discussed. PMID- 1605695 TI - [Vesico-uterine fistula]. AB - We report a case of uterovesical fistula that had been diagnosed by cystoscopy, vaginoscopy and ultrasonography. Fistulorrhaphy via the transperitoneal transvesical approach resolved the passage of urine to the vagina. The decision to perform a conservative or more aggressive approach is determined by the site of the fistula. PMID- 1605696 TI - [Giant lithiasis in left ureterocele. Its endoscopic resolution]. AB - Herein we describe a case of giant calculus in an orthotopic ureterocele in a female patient who had consulted for recurrent left-sided nephritic colic. A plain film of the urinary tract prompted us to suspect a giant calculus, which was confirmed by IVP. Treatment was by endoscopic surgery. The patient has remained asymptomatic one year postoperatively. PMID- 1605698 TI - [Plasmocytoma with asynchronous metastasis. Immunohistological and ultrastructural contribution]. AB - The case of a 37-year-old male who developed multiple asynchronous extramedullary plasmocytoma localizations is reported. The first site involved was the cecum. Other tumors successively arose in the chest wall, testis, buttock, nasal cavity, skin, and mediastinum. The patient died 59 months after initial diagnosis. Light microscopy and ultrastructural studies disclosed a substantial proportion of immature plasmocytes in the different tumors, explaining in part the poor activity of radiotherapy and chemotherapy. Although in many cases this clinical pattern indicates multiple myeloma, investigations failed to detect this condition in the patient reported here. Shortly before the fatal outcome, a peak of IgA kappa globulin was detected in the serum. This immunoglobulin was also identified on tumor cells using immunoperoxidase labeling. PMID- 1605697 TI - [Value of immunohistochemistry with paraffin in malignant lymphoma of the lymphoid tissue associated to the mucosa (MALT) of the digestive tract. Apropos of 8 cases with complete review of the literature]. AB - The authors report eight cases of MALT malignant lymphomas arising in the stomach in four cases, small intestine in two cases and salivary glands in two cases. The gastric lymphomas presented in the form of persistent epigastric pain sometimes lasting for several years, in patients with a mean age of 50.5 years. Gastroscopy revealed recurrent ulcerations in two cases and ulcerated or ulcero-fungating tumours in two cases. The two patients with alpha heavy chain disease, both 21 years of age, presented with chronic diarrhoea. The endoscopic appearance consisted of a pseudopolypoid tumour in one case and a mosaic appearance in the other case. The two salivary gland lymphomas involved the submandibular gland in two patients aged 30 years and 50 years. They presented in the form of nodules 1 and 2 cm in diameter, first detected by the patients two months and four months previously. Histological examination demonstrated the presence of typical lesions of MALT lymphoma with, in particular, the presence of constant lympho-epithelial lesions, various forms of centrocyte-like proliferation, varying degrees of plasma cell differentiation, reactive or residual lymphoid follicles in five cases, which were detected on biopsies in three cases. Immunohistochemistry confirmed the monoclonal nature of the tumour in seven cases, i.e. 87.5% of cases. The application of DBB42 and DNA7 antibodies onto paraffin sections demonstrated the absence of DNA7 labelling of CCL in line with Isaacson's findings in favour of the hypothesis of a non-centrofollicular origin of maltomas. Finally, we observed a single case of recurrence in a women with incomplete resection of the primary gastric tumour. PMID- 1605699 TI - [Colloid cyst of the fourth ventricle. Apropos of a case]. AB - We report a case of a 29 year old patient with a colloid cyst of the fourth ventricule. Colloid cysts or epithelial cysts are exceptional in this site. A common neuroepithelial origin with third ventricule cysts could be explained by similar embryological developments of the prosencephalic and the rhombencephalic roofs. The diagnosis can only be made by histological examination. PMID- 1605700 TI - Hibernoma. A case report. AB - The clinicopathologic features of a hibernoma occurring in a 26 year-old female are reported. The tumor was located in the interscapular region and eventually became painful. Surgical excision was performed and to date, no recurrences have been detected. PMID- 1605701 TI - [Guy Chomette (1926-1992)]. PMID- 1605702 TI - [Immunohistochemical study of cytosolic estrogen receptor-bound protein in breast cancer. Correlation with a biochemical study. Apropos of 107 surgical specimens]. AB - One hundred and seven breast cancers were studied by immunohistochemistry with a monoclonal antibody revealing a protein bound to cytosolic estrogen receptors ERD5 on paraffin embedded tissue. Seventy seven per cent of the cancers were positive with a variable intensity. In half of the cases, the estrogen cytosolic receptors were also determined by biochemistry. The results were similar in 74% of cases. Estrogen receptors were detected by immunohistochemistry in 18.5% of the cancers which were negative on biochemistry. As is well known, the presence of estrogen in 18.5% of the cancers which were negative on biochemistry. As is well known, the presence of estrogen receptors is an important prognostic factor in breast cancer. Our results, together with the simplicity of the immunohistochemical method, should encourage pathologists to include this analysis in the study of surgical specimens of breast cancers. PMID- 1605703 TI - [Stress factors in psychiatric hospitalization]. AB - The incidence of stressful life events in the six months previous to psychiatric hospitalization is studied in a group of patients allotted to different diagnostic categories but which held in common that they were at their first episode of inpatient treatment. The presence of early life events during childhood and of chronic stress during the last year is also investigated. The different kind of responses to LE are described, classified in several categories. The incidence of LE in the patients is compared with that of a group of acute traumatologic hospital inpatients. In every case it has been used the Paykel LE rating scale, the Brown and Harris interview schedule and the GAF. Results are analyzed and their implications in preventive and treatment programs in Mental Health are discussed. PMID- 1605705 TI - [Psychiatry periodicals in Spain up to 1931]. AB - The development of psychiatry, as it happens with other medical specialties, has been linked to that of the journals dedicated to it. They are a good exponent of its state of growing or consolidation. The first psychiatric journal in Spain appeared in 1865 and 27 years later the next one was founded. None of the three journals which existed in the 19th century continued at the beginning of the 20th century. During the first three decades of this century, nine specialized journals were founded, among which the "Revista Frenopatica Espanola" in the first place, and the "Archivos de Neurobiologia" afterwards, were the most outstanding in our country and the "Revista Frenopatica Espanola" was that of the greatest international projection. Although the importance of a constellation of prestigious journals which were not dedicated to psychiatry was decisive for the development of this discipline in our country, the professionals organized themselves in the monographic journals about this subject, linked to mental hospitals. PMID- 1605704 TI - [Therapeutic aspects of agoraphobia]. AB - In this paper we analyzed some aspects about the treatment of agoraphobic patients. We studied the type of professionals, institutions and therapies prescribed to the patients and some practical implications are discussed. PMID- 1605706 TI - [Absence of HIV carriers among long-term psychiatric inpatients]. PMID- 1605707 TI - [More on the sex of the brain]. PMID- 1605708 TI - [Outpatient diagnosis and treatment of patients with anxiety disorder]. AB - The factors found in the approach taken towards the disturbances caused by anxiety on the part of the doctors working outside the hospital environment are analyzed. After studying a sample of 45 patients seen consecutively in the outpatient clinica of a general hospital and evaluating their clinical, evolutive, social-demographical characteristics and the type of medical care received previously, we found an important tendency towards diagnostic error which does not seem to be related to the degree of specialization by the medical practitioner who treated the patient. A profile of a patient having a higher risk of receiving and incorrect diagnosis is elaborated. PMID- 1605709 TI - [CNS-agents: synthesis and properties of 3-anilino-8-oxatropanes]. AB - Reaction of the 8-oxabicyclooctenone and -octanone derivatives 3 and 4 with aniline and metal hydrides yields the 3 alpha-isomers of the aniline derivatives 7 and 8, preferably. The configuration can be determined by NMR-spectroscopy and by cyclization to the scopoline analogue 9b. Depending on the N-substitution the pyran rings of the alpha-isomers are flattened (7,8) or deformed to give a boat conformation (10,11,13). The conformationally restricted aniline derivative 18 can be obtained from 4 with 2-aminobenzaldehyde and diborane, trans-configuration is preferred in 18. Some substrates reveal CNS-effects in mice. PMID- 1605710 TI - Synthesis and inhibitory activities against aminopeptidase B and enkephalin degrading enzymes of ketomethylene dipeptide analogues of arphamenines. AB - Three ketomethylene pseudodideptide analogues [(S)Lys psi(COCH2)(R and S)Phe (14 or 15 and 15 or 14) and (S)Lys psi(COCH2)(xi Trp (19)] of natural arphamenine A [(S)Arg psi(COCH2(R,S)Phe (1)] were easily prepared by a route involving two successive main reactions: a malonic ester alkylation with Z-protected lysine iodomethyl ketone and the introduction of a benzyl or (indol-3-yl)methyl moiety in position 2 of the resulting 4-ketodiester. The isomer of 1 with reversed sequence, (S)Phe psi(COCH2)(R,S)Arg (22) was synthesized by guanidylation and subsequent deprotection of Z-(S)Phe psi(COCH2)(R,S)Orn. The inhibitory effects of compounds 14, 15, 19, and 22, and the related ketomethylene dipeptides (S)Ala psi(COCH2)(R,S)Phe (3), (S)Phe psi(COCH2)(R,S)X [X = Ala (4), Orn (5)] and (S)Trp psi(COCH2)(R,S)Y [Y = Orn (6), Lys (7), Arg (8)] on aminopeptidase B (AP-B), and enkephalin-degrading enzymes [aminopeptidase N (APN) and neutral endopeptidase (NEP)] were compared with that of the model compound 1. PMID- 1605711 TI - [Synthesis of metabolites and enantiomers of prolintane]. AB - The synthesis of 15 possible metabolites of prolintane (1) (Katovit) which is used in the treatment of blood pressure disregulations is described. Furthermore, the preparation of the enantiomers of 1 is reported, starting with R-(+)- and S-( )-phenylalaninol respectively. PMID- 1605712 TI - [Synthesis of alpha-chrysanthemylmethyl-gamma- and delta-lactones with cytostatic activity]. AB - The synthesis of the alpha-chrysanthemylmethylen-gamma- and delta-lactones 7-9, 11, 12 from the lactones 1-3, 5 and that of 10 from 2-oxo-chroman (4) and the aldehyd 6 is described. The compounds 7-9 and 11, 12 show cytostatic activity. PMID- 1605714 TI - Reduction of amidoxime derivatives to pentamidine in vivo. PMID- 1605713 TI - Enantiomerically pure aminoindolizines: bicyclic ergoline analogues with dopamine autoreceptor activity. PMID- 1605715 TI - Stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine]platinum(II) complexes, Part III: Evaluation of the mammary tumor inhibiting properties. AB - Stereoisomeric [1,2-bis(3-hydroxyphenyl)ethylenediamine]platinum(II) complexes produce a strong configuration-dependent inhibition of the hormone sensitive MXT mammary carcinoma of the mouse. Besides an interference in the DNA synthesis in analogy to cisplatin an estrogen level lowering effect is supposed to be the mode of action. The new complexes show also a significant activity on the hormone independent MXT-mammary carcinoma of the mouse. PMID- 1605716 TI - Benzo[b]thiophenes, Part I: Synthesis and antimicrobial activity of benzo[b]thienyl-1,3,4-oxadiazole, -1,2,4-triazoline, and -thiazoline derivatives. PMID- 1605717 TI - Analysis of drugs by polarography, XXXV: The polarographic behaviour of cinolazepam[1-(2-cyanoethyl)-7-chloro-3-hydroxy-5-(2-fluorophe n yl)-1,3-dihydro 2H-1,4-benzodiazepin-2-one] and assay of its tablets. AB - Cinolazepam is reduced at the Dropping Mercury Electrode (DME) over the entire pH range in Britton Robinson buffers (BRB) containing 20% DMF as a solubilizer. A well-defined cathodic wave is obtained over the pH range 3-5, which is very suitable for analytical purposes. The wave was characterized as being irreversible, diffusion-controlled and free from adsorption phenomena. In acid buffers, 4 electrons are consumed in the reduction process, while in alkaline buffers the electrode reaction is somewhat complicated. Tablets containing 40 mg cinolazepam were analysed using the polarographic and a developed HPLC method. The results obtained with both methods are in good accordance as revealed by statistical analysis. The details of the complicated mechanism of the reduction process at the DME are still under investigation but elucidated in principle. PMID- 1605718 TI - [The binding of 5-fluorouracil to serum protein fractions, erythrocytes and ghosts under in vitro conditions]. AB - The binding of 5-fluorouracil (1) to erythrocytes and to serum proteins under in vitro conditions was investigated. The binding rate of 1 to erythrocytes is dose independent and amounts from 16.8 to 31.7% (concentration range 1 to 20 micrograms/ml). The mean coefficient of partition for erythrocytes is 0.25 (+/- 0.03), no binding to ghosts was observed. 1 is bound at about 4% to proteins, whereby 0.7% are bound to alpha-globulin, 0.8% to beta-globulin, 1.6% to gamma globulin, and 0.8% to albumine. The mean partition coefficient for proteins is 0.04 (+/- 0.006). PMID- 1605719 TI - [Pharmacokinetics of 5-fluorouracil in erythrocytes following i.v. administration]. AB - The in vivo binding of the antineoplastic agent 5-fluorouracil (1) to erythrocytes in the whole blood of patients was investigated. The vascular availability of 1 is influenced by erythrocytes at 38.6 +/- 7.2% (calculated as AUC0-60-values), the coefficient of partition is 0.65 +/- 0.18. In comparison with serum, the volume of distribution and the total clearance are elevated by the erythrocytes, the half-lives of the compartment distribution and of the terminal elimination are not influenced. PMID- 1605720 TI - [Synthesis, reactions, and CNS-actions of 6,7-annealed 8-oxatropane derivatives]. AB - The butadiene derivatives 10a-c react with the oxa-bicyclooctanone 9 to give the cyclohexene annulated oxatropanes 11a-c. The acetoxyderivatives 11b and 11c can be transformed into the cyclohexadiene or benzene derivatives 13 and 12, respectively. 11a reacts with HN3 to afford the tricyclic oxazepanone 14 which can be reduced to give 15a; the oxime-tosylate 16b reacts with Al(CH3)3/DIBALH to yield the oxazepane 15c. Treatment of the oxabicyclooctanes 9 and 19 with benzonitrile oxide or diazomethane affords the isoxazoline or pyrazoline annulated oxatropanes 21, 22, and 20, respectively. 21 was reduced to the amino alcohol 23. 15c and 23 show CNS-activity in the mouse. PMID- 1605721 TI - Synthesis and preliminary pharmacological study of thiophene analogues of the antipyretic and analgesic agent ethenzamide. AB - A preliminary pharmacological study of a thiophene analogue 1b of the analgesic and antipyretic agent Ethenzamide and of a closely related compound 1a showed that a great similarity exists among Ethenzamide and the thiophenic compounds for analgesic, antipyretic, ulcerogenic, hypothermic, and sedative effects. However, the acute toxicity in mice for the thiophenic compounds is notably higher than that of Ethenzamide. PMID- 1605722 TI - Dichloro-[1-(hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes: testing on the human ovarian cancer cell lines NIH: OVCAR3 and SK OV 3. AB - The diastereoisomeric dichloro-[1-(2-, 3- and 4-hydroxyphenyl)-2 phenylethylenediamine]platinum(II) complexes were tested on two human ovarian cancer cell lines NIH: OVCAR-3 and SK-OV-3, both resistant against cisplatin. Dichloro-[threo-1-(3-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) (threo-5 PtCl2) proved to be the most active representative of the new series, producing cytocidal effects at a concentration range of 2.5 to 5.0 microM on the NIH: OVCAR 3 cell line. On the more resistant SK-OV-3 cell line, threo-5-PtCl2 was only moderately active, while in combination with BSO, a GSH level lowering compound, threo-5-PtCl2 showed a strong synergistic effect. PMID- 1605723 TI - Acute lesions in rats caused by 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) or nitromin: a comparison with rates of reduction in microsomal systems from target organs. AB - Pathological lesions to male Fischer rats were investigated 24 h after the administration of 3-amino-1,2,4-benzotriazine-1,4- dioxide (SR 4233) or nitromin, two compounds which need to undergo bioreductive activation in order to exert their toxic effects. Although SR 4233 reduction leads to a putative free radical species while with nitromin a bifunctional alkylating agent is formed, in both instances, the bone marrow was a major target organ. However, the response of other organs to these compounds differed. SR 4233 caused lesions to the olfactory epithelium, liver, kidney and thymus. Nitromin caused focal haemorrhages on the intestine, which were reduced in germ-free rats. Rates of reduction of SR 4233 or nitromin were determined under anaerobic conditions using microsomal preparations from target tissues. With SR 4233 as a substrate, reductase activities were highest in the olfactory epithelium, 6 fold higher than in the liver. SR 4233 reductase activities generally correlated with those of NADPH:cytochrome c reductase or the concentration of cytochrome P-450 reductase protein in the affected organs while with nitromin, there appeared to be no such relationship. The present results support the concept that the expression of pathological damage in vivo is a multifactorial process and does not directly correlate with initial rates of reduction of either drug determined in vitro. PMID- 1605724 TI - Acetaminophen nephrotoxicity in male Wistar rats. AB - Acute acetaminophen (APAP) nephrotoxicity was studied in male Wistar rats 1 h after different APAP single doses (200, 500 and 1000 mg/kg body wt, i.p.). Significant impairments in glomerular filtration rate (GFR) and clearance of p aminohippuric acid (ClPAH) were observed in a dose-dependent way, although tubular parameters measured, water and electrolyte fractional excretion, remained at control values, while the urine to plasma osmolality ratios (Uosm/Posm) were diminished in APAP-1000 rats (control = 2.93 +/- 0.20, APAP-1000 = 1.40 +/- 0.04). The time course of renal function was also studied in APAP-1000 mg/kg treated animals; parallel impairments were observed in GFR, ClPAH and tubular functions. Maximal alteration was observed at 16 h and restorement began at 24 h post-injection. Glucose renal handling, either at low or at high tubular glucose loads, remained at control values. Thus, our data suggest that the early stage of acetaminophen nephrotoxicity might be due to renal hemodynamic changes which might induce an alteration in tubular function principally in distal structures of medullary tissue, as shown by the Uosm/Posm results. These effects occurred coupled with a diminution in hepatic glutathione (GSH) levels at every APAP dose and in renal GSH levels in APAP-1000 mg/kg-treated rats. Moreover, renal damage was observed both in the presence or absence of hepatic damage. PMID- 1605726 TI - Altered lung function in rats after subacute exposure to n-butyl isocyanate. AB - The objectives of this study were to use pulmonary function tests, blood gas measurements and bronchoalveolar lung lavage (BAL) to characterize lesions in the respiratory tract of young adult male Wistar rats as a result of a 5-day exposure (6 h/day) to 0, 1.1, 6.2, 15 or 26 mg n-butyl isocyanate (n-BIC)/m3 air. Further objectives were to probe the diagnostic sensitivities of these procedures in comparison with more traditional evaluations (clinical observation, lung weight, histopathology). Measurements were performed during post-exposure weeks 2 and 5. Most rats exposed to 26 mg/m3 died or were sacrificed in a moribund state during post-exposure week 2. All other rats survived the exposure regimen. In rats exposed to 15 and 26 mg/m3 a significant decrease in body weight, laboured breathing, hypoactivity, nasal discharge, cyanosis, and hypothermia were observed. Pulmonary function measurements revealed increased total lung capacity (TLC) and residual volume (RV), decreased forced expiratory flow rates and quasi static compliance in rats exposed to 26 mg/m3. At the end of the observation period rats exposed to 6.2 and 15 mg/m3 air were hyperresponsive to an acetylcholine bronchoprovocation aerosol. Arterial blood gas measurements revealed an arterial hypoxia and an increase in venous admixture, suggesting a severe mismatch of the ventilation-perfusion relationship. Biochemical and cellular components in BAL fluid (BALF) indicated a concentration dependent and protracted increase of polymorphonuclear leucocytes and further inflammatory parameters. In the 1.1 mg/m3 group BALF parameters were not significantly elevated. The major histopathological lesions of the lung were thickening of septa, emphysema, and intra-alveolar oedema in rats exposed to 26 mg/m3.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605725 TI - Acetylator genotype-dependent N-acetylation of arylamines in vivo and in vitro by hepatic and extrahepatic organ cytosols of Syrian hamsters congenic at the polymorphic acetyltransferase locus. AB - Our laboratory recently reported the successful construction of homozygous rapid (Bio. 82.73/H-Patr) and homozygous slow (Bio. 82.73/H-Pat(s)) acetylator congenic Syrian hamsters. These hamsters are isogenic except for the polymorphic acetylator gene locus (Pat) and perhaps other closely linked loci. The purpose of the present investigation was to assess the expression of acetylator genotype both in vivo and in vitro in a variety of hepatic and extrahepatic organ cytosols. Levels of arylamine N-acetyl-transferase were generally high and in the relative order: liver greater than colon greater than kidney greater than pancreas greater than prostate, urinary bladder, and lung. However, an acetylator gene dose-response was clearly expressed in each tissue, with highest levels in homozygous Patr acetylators, intermediate levels in heterozygous Patr/Pat(s) acetylators, and lowest levels in homozygous Pat(s) acetylators. The magnitude of the acetylator genotype-dependent differences in N-acetyltransferase activity were substrate specific, wherein p-aminobenzoic acid showed the largest differences and p-aminophenol the smallest. The N-acetylation of p-aminobenzoic acid in vivo also reflected acetylator genotype in the congenic hamsters. These results further document the successful construction of rapid and slow acetylator congenic hamsters which should prove very valuable in future studies to assess the role of acetylator genotype in the toxicity and carcinogenicity of arylamine chemicals. PMID- 1605727 TI - Endotoxin tolerance and polymyxin B modify liver damage and cholestasis induced by a single dose of alpha-naphthylisothiocyanate in the rat. AB - A single oral dose of alpha-naphthylisothiocyanate (ANIT) induces intrahepatic cholestasis and endotoxemia in the rat. To assess if a pathogenic relationship between endotoxin and ANIT-induced liver injury could be postulated, rats were pretreated by either induction of endotoxin tolerance, or with the anti-endotoxin agent polymyxin B. A single oral dose (10 or 20 mg/100 g body wt) of ANIT was then given to ascertain whether these methods of modifying endotoxicity would protect the animals against ANIT damage. Both pretreatments significantly reduced the incidence of endotoxemia after ANIT administration, as detected by either lead acetate enhancement method or the Limulus gelation test (LGT). The lethality of a single 20 mg/100 g body wt dose of ANIT was reduced from 55% to 15% by polymyxin B administration, and to 10% by an endotoxin-tolerant state. Moreover, when 10 mg/100 g body wt ANIT was given none of the animals died in 10 days, and the serum levels of bilirubin, alkaline phosphatase (AlPh), gamma-glutamyl transferase (gamma-GT), and transaminases (evaluated 1, 2, and 5 days after treatments) were significantly lower in the endotoxin-tolerant or polymyxin B administered rats; this biochemical protection was mirrored in the lack of histological alteration. The results demonstrate that the modification of endotoxicity offers significant protection against acute liver damage induced by ANIT. Thus the development of endotoxemia may play a pathogenic role in ANIT induced liver injury. This conclusion is supportive of the hypothesis that endotoxins are necessary for the hepatotoxic agent to exert its full effects. PMID- 1605728 TI - Inhibition of the liberation of arachidonic acid by cadmium ions in rabbit alveolar macrophages. AB - The effects of CdCl2 on the liberation of arachidonic acid (20:4) from membrane phospholipids of A23187-stimulated rabbit alveolar macrophages and on the activity of phospholipase A2 (PLA2) in a cytosolic fraction were studied. Alveolar macrophages were prelabeled with [3H]arachidonic acid (20:4) and then treated with A23187. This treatment resulted in a remarkable increase in the liberation of [3H]20:4 from their phospholipids. Exposure of cells to Cd2+ inhibited the liberation of [3H]20:4 in a dose-dependent manner. Liberation of [3H]20:4 from cell lipids was calcium dependent and the inhibitory effect of Cd2+ competed with the stimulatory effect of Ca2+. When Ca2+ was removed from the incubation medium, Cd2+ did not influence the liberation of [3H]20:4. Entry of 45Ca2+ into cells was enhanced by treatment of A23187. However, Cd2+ did not influence the cellular uptake of 45Ca2+. Treatment with A23187 markedly enhanced entry of 109Cd2+ into cells. The effect of Cd2+ on the activity of phospholipase A2 was determined with 1-palmitoyl-2-[14C]arachidonoyl-sn-glycero-3 phosphocholine as substrate. Calcium-dependent activation of PLA2 was observed and Cd2+ inhibited activation in a dose-dependent manner. These results suggest that exposure of alveolar macrophages to Cd2+ causes a reduction in the rate of liberation of 20:4 from cell lipids, as a possible result of the inhibition of PLA2 activity by Cd2+. PMID- 1605729 TI - N-nitrosodialkylamine dealkylation in reconstituted systems containing cytochrome P-450 purified from phenobarbital- and beta-naphthoflavone-treated rats. AB - Five cytochrome P-450 forms were purified from livers of rats pretreated with phenobarbital (PB) or beta-naphthoflavone (BNF), and the oxidative dealkylation of N-nitrosodialkylamines by the reconstituted cytochrome P-450 systems was measured. PB-II (P450IIB1) showed very high N-nitrosomethybutylamine (NMBA) debutylase activity, high NMBA demethylase activity and high N-nitrosomethyl benzylamine (NMBeA) debenzylase activity, suggesting that the increase following PB treatment in hepatic microsomal NMBA debutylation and NMBeA debenzylation was due to the induction of PB-II. BNF-H (P450IA2) showed very high NMBA debutylase and high NMBeA debenzylase activities, and BNF-L (P450IA1) showed NMBA debutylase and high NMBeA debenzylase activities. These results suggested that the increase by BNF pretreatment in hepatic microsomal NMBA debutylation was due mainly to the induction of BNF-H and in some part to that of BNF-L. PB-II also showed very high dealkylation activity of lipophilic N-nitrosodialkylamines with long alkyl moieties. On the other hand, BNF-H dealkylated N-nitrosodipropylamine (NDPA), N nitrosomethylbutylamine (NMBA) and N-nitrosoethylbutylamine (NEBA) at higher rates than N-nitrosodibutylamine (NDBA). BNF-L dealkylated NEBA at higher rates than NMBeA and NDBA. These results reveal that substrate specificity of each cytochrome P-450 form in N-nitrosodialkylamine metabolism is different from each other and several forms of cytochrome P-450 support each N-nitrosamine dealkylase activity in mammalians. PMID- 1605730 TI - Efficacy of various oximes against GF (cyclohexyl methylphosphonofluoridate) poisoning in mice. AB - The efficacy of oxime (HI-6, toxogonin or PAM Cl) therapy against GF (cyclohexyl methylphosphonofluoridate) poisoning was assessed in mice. It was found that the combinations of atropine and either toxogonin or HI-6 were effective therapies against GF poisoning. PAM therapy was ineffective. HI-6 was the only oxime which reactivated GF inhibited acetylcholinesterase. This might explain the reason why the HI-6 treated mice appeared to recover more quickly from the incapacitating effects following GF poisoning. PMID- 1605731 TI - Effect of preinduction of metallothionein on paraquat toxicity in mice. AB - The effect of pretreatment with metallothionein (MT)-inducing metals (Zn, Cu, Bi, Co, Cd or Hg) on paraquat (PQ) toxicity was investigated in mice. PQ lethality was remarkably reduced by pretreatment with the above MT-inducing metals. The protective effect of pretreatment with these metals on PQ lethality was significantly correlated with MT levels in the lung, a target tissue of PQ toxicity, in mice administered MT-inducing metals, but not with MT in the liver or kidney. The increase in pulmonary lipid peroxidation in mice treated with PQ was significantly inhibited by Zn pretreatment. Zn was the most effective of the MT-inducing metals used in this experiment in protecting mice against PQ lethality. Of those monitored, the only pulmonary free radical scavenging factor increased by Zn pretreatment was MT. Other free radical scavenging factors (activities of superoxide dismutase, glutathione peroxidase and catalase, and concentration of non-protein thiols level) were not influenced by Zn treatment. These results indicate that the induction of pulmonary MT protects against the lethality and lung toxicity of PQ. Pulmonary MT may scavenge free radicals produced by PQ, thereby protecting against lethal pulmonary toxicity. PMID- 1605732 TI - Evaluation of prenatal aldrin intoxication in rats. AB - The aim of the present study was to evaluate the impact of prenatal exposure to low doses of aldrin on physical and behavioral developments of rats (1-21 days old). To detect the possible persistent adversities produced by this exposure, the animals were also tested when adults (90 days old). Plasma determinations of both aldrin and its metabolite dieldrin and histopathological evaluations of brain slices were also performed in adult animals. Pregnant female rats were subcutaneously (s.c.) treated with aldrin (1.0 mg/kg) or with its vehicle (0.9% NaCl solution plus Tween-80) from day 1 of pregnancy until delivery. Results show that prenatal aldrin administration was able to decrease the median effective time (TE50) for incisor teeth eruption and to increase the TE50 for testes descent; other parameters indicative of physical development were not modified. Aldrin and dieldrin were not found in plasma of the adult rats; no differences were observed between control and experimental rats in the cellular and structural organization of the cerebral cortex neurones. Prenatal aldrin administration produced no impairment of adult animal's behavior in an avoidance learning test; nevertheless, the locomotor frequency of the experimental rats was higher than that of controls at 21 and 90 days old. When adults, these experimental rats had their performance in a hole-board apparatus (total number and duration of head-dips) also higher than that of the control ones. It was concluded that prenatal aldrin exposure induced not only developmental changes in the rat pups but also persistent behavioral alterations in adulthood, when the pesticide was not present in these animals. PMID- 1605733 TI - Regional brain distribution of toluene in rats and in a human autopsy. AB - Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10,000 ppm) for 0.5 h or by oral dosing (400 mg/kg), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR: 2.66) and the lowest in the hippocampus (BBCR: 1.47). PMID- 1605734 TI - Localization of mercury in CNS of the rat. V. Inhalation exposure to metallic mercury. AB - The autometallographical technique has been used to determine the distribution and cellular localization of mercury deposits in the Wistar rat CNS after exposure to elemental mercury vapor (50-550 micrograms Hg/m3 of air for 4-24 h). In animals exposed to 50 micrograms Hg/m3 for 8 h, silver-enhanced mercury grains were confined to the capillary walls. Increasing the concentration of mercury to 500 micrograms Hg/m3 caused mercury staining to appear in neurons in the corpus striatum, mesencephalic nucleus of the trigeminal nerve and cerebellar deep nuclei. In the spinal cord, mercury appeared primarily in the motoneurons of lamina IX. Following exposure to 550 micrograms Hg/m3 for 12 h mercury was additionally detected in the ependyma. Animal exposure to 550 micrograms Hg/m3 for 24 h resulted in visible mercury deposits in the cerebellar and cerebral cortices. In the cerebral cortex, mercury was present in neurons populating lamina III in the isocortex. No mercury was detected in the allocortex. In the cerebellar cortex, mercury staining was limited to the Purkinje cells. Neurons in the thalamus contained heavy accumulations of mercury. Heavy staining for mercury was detected in lung alveolar macrophages in sections prepared from animals exposed to 550 micrograms Hg/m3 for 24 h. In animals exposed to 500 micrograms Hg/m3 or more, the primary target cells were the neurons, but glia cells also contained scattered mercury deposits. Ultrastructurally, mercury deposits were detected in the lysosomes. PMID- 1605735 TI - Aluminium modifies the electrical response of neuroblastoma cells to a short hypertonic pulse. AB - The effect of aluminium (50-100 micrograms/ml) on the electrical response of N1E 115 neuroblastoma cells to a short hypertonic pulse was examined using conventional electrophysiological techniques and computer assisted analysis. Application of a small dose of hypertonic solution in the vicinity of the cell evoked depolarization of the membrane potential and a biphasic change in input resistance: an initial increase followed by a profound decrease. Upon washout of the hypertonic stimulus, repolarization of membrane potential and complete recovery of the input resistance were observed. In the presence of aluminium application of hypertonic solution had a reversible effect which showed a prolonged duration of the response without a change in its amplitude. It is suggested that the retardation in recovery from hypertonically induced shock may be due to rigidification of the plasma membrane in the presence of aluminium. Possible implications to human diseases associated with accumulation of aluminium in brain tissue are discussed. PMID- 1605737 TI - Frequency of morphological phage descriptions. AB - Bacteriophages are listed by morphotypes and host genera. At least 4.007 phages, belonging to 13 virus families, have been described since 1960. About 3,850 phages (96%) are tailed and 154 phages (4%) are cubic, filamentous, or pleomorphic. Siphoviridae or phages with long noncontractile tails constitute 60% of tailed phages. Phages are found in over 100 bacterial genera including archaebacteria and rickettsiae. Their distribution is very uneven and probably reflects the evolutionary history of bacteria. PMID- 1605736 TI - Secretion of human chorionic gonadotropin in superfused young placental tissue exposed to cadmium. AB - The effect of various concentrations of cadmium (Cd) in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) in first-trimester placental explants, after 6 or 24 h incubation, employing both static and dynamic systems was examined. Later the unbound Cd was washed for 45 min with fresh medium devoid of Cd, followed by superfusion with the latter medium for 75 min, during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude (MPA), pulse frequency (PF) and the area under the hCG secretion curve (AUC). The results indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Cd. Maximal hCG secretion was observed after 24 h exposure of explants to 6 micrograms of the metal/ml. Both the MPA and AUC parameters showed a statistically significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, the value for the mean hCG secretion being comparable to that observed for 0.75 micrograms/ml. After 6 h incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Cd levels. These results indicate that Cd may affect the normal placental function, as reflected in its hCG secretion pattern. PMID- 1605738 TI - Molecular evolution of human paramyxoviruses. Nucleotide sequence analyses of the human parainfluenza type 1 virus NP and M protein genes and construction of phylogenetic trees for all the human paramyxoviruses. AB - The nucleotide sequences of the NP and M genes of human parainfluenza type 1 virus (HPIV-1) were determined. The NP gene was 1677 nucleotides long excluding polyadenylic acid. The NP gene contained a single large open reading frame (ORF), which encoded a polypeptide of 524 amino acids with a calculated molecular weight of 57,736. The M gene 1173 nucleotides long excluding the poly(A) tract and the sequence also contained a single large ORF which encoded a polypeptide of 348 amino acid with a molecular weight of 38,445, which was inconsistent with 28 kDa previously determined by SDS-PAGE. We aligned the deduced HPIV-1 NP and M protein sequences with 12 and 13 other paramyxoviruses, respectively, suggesting that a common tertiary structure was found in the NPs or Ms of HPIV-1, Sendai virus (SV), HPIV-3 and BPIV-3 and that other common structure was also maintained in these proteins of HPIV-2, SV 41 and 5, MuV, HPIV-4. Phylogenetic trees were constructed for the NP and M proteins of all the paramyxoviruses of which nucleotide sequences had been previously reported. Paramyxoviruses could be subdivided into two groups, i.e., PIV-1 group and PIV-2 group; the former group is composed of HPIV-1, SV, HPIV-3 and BPIV-3, and the latter group consists of HPIV-2, SV 41, SV 5, MuV, HPIV-4 A and HPIV-4 B. PMID- 1605739 TI - The 3' terminal sequence of a human astrovirus. AB - We have determined the sequence for 1,000 bases from the 3' terminus of a human astrovirus serotype 1 isolated in Newcastle. This is the first sequence reported for a representative of this virus family. We find one open reading frame which terminates 83 bases from a poly A tail. The 3' non-coding-region has similarities to some picornavirus termini. However the amino acids specified by the coding region have no significant homology to the picornavirus protein 3D, encoded at the 3' terminus of these viruses. Northern blot analysis of intracellular virus specific RNAs revealed one size of transcript which corresponded to full-length virus RNA. Available data thus indicate that astroviruses may resemble picornaviruses in replication strategy. PMID- 1605740 TI - Characterization of viral DNAs from cells infected with chicken anaemia agent: sequence analysis of the cloned replicative form and transfection capabilities of cloned genome fragments. AB - The viral DNAs induced by the unclassified animal virus, chicken anaemia agent (CAA), during replication in MDCC-MSB 1 cells have been investigated. Analyses after S1 nuclease, restriction endonuclease and denaturation treatments indicated that infected cell extracts contained genome-size, single-stranded DNA (M(r) 2.3 kb), closed and open circular, double-stranded replicative form (RF) DNAs (M(r) 2.3 kbp) and a population of smaller double-stranded DNAs (M(r) 0.8 kbp). Recombinant plasmids containing 2.3 kbp CAA RF fragments cloned at the PstI, BamHI and EcoRI sites failed to transfect MDCC-MSB 1 cells. However, one plasmid, which contained two 2.3 kbp CAA RF fragments ligated in tandem at the PstI site, and cloned 2.3 kbp PstI, BamHI and EcoRI fragments, excised from their respective plasmids by restriction endonuclease digestion, were capable of transfection. The nucleotide sequence of the circular genome (2298 bp) of the Cux-1 isolate of CAA has indicated the presence of three overlapping open reading frames (ORFs) of 52 kDa, 24 kDa and 13 kDa on one strand. The existence of these ORFs was corroborated by analyses of partial sequences from three other isolates. The non coding region of the CAA genome contained sequences with putative regulatory function. These results are discussed in relation to the "rolling circle" model of DNA replication. PMID- 1605741 TI - A comparison of serological relationships among five ruminant alphaherpesviruses by ELISA. AB - Using enzyme-linked immunosorbent assays the cross reactivity of bovine herpesvirus-1.1, bovine herpesvirus-1.2, caprine herpesvirus-2, cervine (red deer) herpesvirus-1 and rangiferine (reindeer) herpesvirus-1 has been examined using rabbit hyperimmune antisera and convalescent cattle and red deer field sera. Significant cross-reactivity among all the five viruses was demonstrated. A detailed analysis showed that: (1) the two bovine herpesviruses are most closely related, (2) the cervine, caprine and rangiferine viruses are more closely related to the bovine viruses than they are to each other, (3) the cervine herpesvirus is more related to the bovine herpesvirus than to the rangiferine or caprine herpesviruses and (4) the rangiferine virus is more related to the cervine virus than to the bovine and caprine viruses. Cattle and red deer sera reacted most strongly with the bovine and cervine viruses respectively. PMID- 1605742 TI - Morphogenesis of African swine fever virus in monkey kidney cells after reversible inhibition of replication by cycloheximide. AB - The late cytoplasmic phases of African swine fever virus (ASFV) morphogenesis in monkey kidney cells have been studied by transmission electron microscopy, focusing attention on the synthesis of viral envelopes. Morphogenesis was studied after reversible cycloheximide blockage of monkey kidney cells infected with ASFV. ASFV appears to synthesize its external and internal envelopes within the cellular cytoplasm, at the same time as the capsid is formed, with intracellular and extracellular virions showing similar structure and polypeptide composition. PMID- 1605743 TI - Major sequence variations in the N-terminal region of the capsid protein of a severe strain of passionfruit woodiness potyvirus. AB - The deduced coat protein sequence of the K strain of passionfruit woodiness virus differed significantly, particularly in the N terminus, from the sequences of the TB, M, and S strains of the virus. An antiserum that reacted strongly with the TB, M, and S strains reacted very poorly with the K strain. PMID- 1605744 TI - The experience of an apprentice independent midwife. PMID- 1605745 TI - Prenatal education--how effective is it? AB - Are provision of knowledge and skills the major factors to influence behaviour changes that will in turn affect psychological and physiological outcomes in pregnancy and childbirth? This paper argues that courses for expectant parents must not be considered or promoted in isolation. Rather, they should be viewed as part of a complex, interrelated structure of variables that serve to create, influence, modify, support and reinforce factors considered to be indicators of favourable birth outcomes. The potential for health promotion activities is highlighted and problems of marketing, access, and restrictive obstetric management practises emphasised. Relevant research is discussed and areas for urgent action and further research are identified. PMID- 1605746 TI - A conceptual framework for a midwifery curriculum in institutes of higher education. PMID- 1605747 TI - Response of the oral tissues to prolonged uninterrupted coverage by a removable partial denture. Case report. AB - The response of hard and soft oral tissues to prolonged uninterrupted wearing of a removable partial prosthesis in a Nigerian patient is discussed. To our knowledge only one case has been reported in the literature. In this case additional mucosal changes to the reported caries-free pattern is discussed. PMID- 1605748 TI - Surgical management of drooling. Case report. AB - Drooling occurs when excessive quantities of saliva dribble from the opened mouth. This distressing condition affects many mentally handicapped patients who are unable to effectively clear their normal salivary flow by swallowing. Any method employed for the control of drooling must still allow a sufficient volume of flow for mastication, deglutition and oral hygiene. Surgery is generally indicated for marked or severe cases of drooling and Wilkie's operation involving redirection of the parotid flow into the oropharynx is the most commonly performed surgical procedure. This operation may be combined with bilateral removal of the submandibular salivary glands if the problem is severe. PMID- 1605749 TI - Assessment of the cariogenic potential of fruit fingers, muesli bars and jelly beans. AB - Intra-oral tests of a fruit bar, a muesli bar and jelly beans were performed to establish their cariogenic potential by means of enamel hardness changes. Little difference was found when the fruit finger and muesli bar were compared. Surprisingly, the jelly beans did not produce a greatly increased degree of softening when compared with the fruit fingers. Statistical significance was not reached in either of the experiments carried out. PMID- 1605750 TI - Modulation of human neutrophil adherence by oral bacteria. AB - Polymorphonuclear neutrophils (PMNs) comprise over 90 per cent of leukocytes in the oral cavity. Although these phagocytic cells have primary defence roles in the gingiva, their stimulation by micro-organisms may also cause substantial tissue damage due to the release of lysosomal enzymes and oxygen radicals. Adherence of PMNs to the endothelium and their subsequent diapedesis and egress to areas of infection are considered early vital events in the inflammatory process. In this study, oral bacteria were screened to determine their direct effects on PMN activation using an in vitro method of measuring PMN adherence to Dacron fibres. Most of the bacteria investigated increased PMN adherence, indicating their potential to cause tissue damage through the release of PMN lysosomal enzymes and other products. In contrast, Bacteroides species suppressed PMNs, indicating their ability to circumvent the phagocytic cells, thus gaining a potential advantage in dental colonization. The modulatory effects of oral bacteria on PMN activation may have significant roles in the immunopathogenesis of oral disease. PMID- 1605751 TI - Dental treatment and dental health. Part 1. A review of studies in support of a philosophy of Minimum Intervention Dentistry. AB - An international movement emerged in 1986-1987 which heralded a major change in the role of conservative dentistry. This shift was away from the traditional operative dentistry, with its relatively frequent replacement of restorations, to a concept of 'Minimum Intervention Dentistry', which advocates the use of adhesive dental materials, remineralization techniques and monitoring of initial carious lesions. The move away from some of Black's concepts started as investigations examined the dental health of patients in the National Health Service of Great Britain. These investigations, and the report of the Committee of Enquiry into Unnecessary Dental Treatment, have resulted in an extensive re education programme being initiated by the British Department of Health and Social Security in conjunction with the British Dental Association. This paper, and a subsequent one, were written to enable widespread dissemination of these ideologies to Australian practitioners. While they may appear provocative to some, these papers were merely meant to stimulate discussion on the implications of this research for dentistry in this country. In this paper the results from the British investigations are presented, as is a discussion of some of the outcomes of this and other related research. PMID- 1605752 TI - Challenges facing dental schools in Australia. PMID- 1605753 TI - Towards an Australasian Association of Schools of Dentistry. PMID- 1605754 TI - Why an Australasian Association of Schools of Dentistry? PMID- 1605755 TI - Direct posterior composite resin restorations: a review. 1. Factors influencing case selection. AB - The principal factors that influence case selection for direct composite resin restorations in posterior teeth are discussed. These include the perceived preference for tooth-coloured aesthetics, survival rate and replacement of posterior composites, clinical problems and concerns such as occlusal surface defects and the numerous effects of the material's polymerization contraction, and the availability of alternative tooth-coloured techniques for restoring posterior teeth. Specific guidelines in case selection are suggested. A subsequent paper reviews controversial aspects of the restorative technique for posterior composites and, on this basis, defines important principles in the clinical technique. PMID- 1605756 TI - Dimensional accuracy of small gold alloy castings. Part 4. The casting ring and ring liners. AB - The role of the casting ring and its asbestos liner is discussed. Asbestos as a liner has now largely been replaced by two alternative materials, one based on cellulose and the other on ceramic fibres. The limited literature on the effect of these newer materials on casting accuracy is also reviewed as their introduction may require significant changes in the traditional technology of dental casting. PMID- 1605758 TI - Menopause and preventive medicine. PMID- 1605757 TI - Maxillary ameloblastoma. Case report and review of the literature. AB - A case of maxillary ameloblastoma is presented. A non-healing, asymptomatic ulcerative lesion in the maxillary tuberosity region did not respond following relief of physical irritation. The clinical appearance of the lesion was compatible with that of a malignant tumour, but the histopathology was consistent with a diagnosis of ameloblastoma of the maxilla. PMID- 1605759 TI - Common problems with hormone replacement therapy. AB - The management of the perimenopausal or menopausal woman should include providing facts about the treatment, allaying her fears and gaining some idea of her attitude to hormone therapy. These factors, plus individual treatment, result in improved patient compliance and successful management. PMID- 1605760 TI - HRT and the cardiovascular system. AB - Oestrogen is cardioprotective for women. Not only does it have a beneficial effect on the circulating blood lipid fractions, but it is now established that oestrogen has a positive influence in preventing the deposit of cholesterol in the arterial endothelium. It also induces vasodilation, increases peripheral blood flow and leads to a fall in blood pressure. The use of oestrogen to reduce cardiovascular disease far outweighs any potential adverse changes. PMID- 1605761 TI - Update on osteoporosis. AB - Osteoporosis is an increasing and major public health problem as our population ages. Advances in our understanding of osteoporosis have been facilitated by the advent of accurate and precise methods of bone density measurement. Developments in therapy include transdermal oestrogens, nasal calcitonin and bisphosphonates. The most important principles of management involve maximising bone mass in early adult years and preventing postmenopausal bone loss by oestrogen therapy. PMID- 1605762 TI - Treatment options and menopause regimens. AB - Treating a woman with menopausal or perimenopausal problems is rewarding nd challenging, aided these days by the range of hormones, hormone combinations and delivery systems available. Keeping the following points in mind should improve treatment outcomes: Careful pretreatment assessment. Explanation of benefits and risks. Individualise therapy. Allow about 6 months to stabilise therapy. Regular follow up. Oestrogen only therapy for the woman with a uterus. Combined continuous oestrogen-progestogen therapy await further studies. Continue progestogen therapy for 2 to 3 years after ceasing implant therapy in a woman with a uterus. Severe side effects of progestogen may necessitate oestrogen-only therapy, with regular yearly endometrial biopsy. Duration of therapy is variable, but it may be long term for maximal prevention. PMID- 1605763 TI - Sex after fifty. AB - Society has always been uncomfortable in discussing the sexual needs of the older person, however, sexual activity can give older people a sense of continued strength and renewal. General practitioners are in a unique position to promote a positive attitude about sex and ageing, so that older patients can remain sexually active for as many years as possible. PMID- 1605764 TI - Premature menopause management. AB - Premature menopause is most commonly iatrogenic, but may be due to an autoimmune or other ovarian disorder, or it may be idiopathic. The diagnosis is established by a raised serum FSH. Fertility can only be reliably achieved using donor oocytes; otherwise oestrogen replacement therapy should be offered. PMID- 1605765 TI - Summary of the WONCA/COOP International Health Assessment Field Trial. The Dartmouth COOP Primary Care Network. AB - This paper describes an international clinical feasibility trial conducted by WONCA in seven countries with the basic objective of increasing understanding of patient health. It was found that the Charts were understood by most patients and doctors found them useful. They produced good discrimination and different profiles for different conditions. Significant variations were noted among participating countries, probably reflecting doctor and patient selection as well as true cultural or ethnic differences. PMID- 1605766 TI - Capitation: a service by another name. AB - Fee for service and capitation systems are usually regarded as different methods of medical remuneration, however, they can be seen to differ mainly in the degree to which they 'bundle' or 'package' medical services. A capitation system for general practice services in Australia could be established by the creation of a Medicare item and benefit for a year's general practice care. This would allow doctors to assess the benefits of capitation without a total and potentially traumatic commitment, and may encourage innovation in the efficient delivery of primary health care. PMID- 1605767 TI - Acute neck strain--the value of judicious early mobilisation. AB - The author's own experience of acute neck strain (whiplash) is outlined. He found that gentle mobilisation at the earliest practicable opportunity greatly assisted healing. PMID- 1605768 TI - A comparison of two methods of breastfeeding management. AB - This study has demonstrated that, in a small group of 58 mothers, specific advice focused on establishing easier patterns of breastfeeding resulted in more of them continuing to breastfeed their babies for a longer period post-partum, with a less intense feeding pattern and the use of fewer complementary bottles of formula or other liquids, than did those given only the standard advice about breastfeeding. Current advice might be reviewed to continue to encourage demand breastfeeding but to emphasise the establishment of easier patterns of breastfeeding that optimise the mother-infant interaction. PMID- 1605769 TI - Measles vaccination failure--cause for concern? AB - The author describes a propagated epidemic of measles virus infection on the north-west coast of Tasmania. Almost 20 per cent of children between the ages of 1 year and 15 years contracted the illness, 45 per cent of whom were previously vaccinated. A retrospective cross-sectional study was conducted to assess the incidence of infection and the vaccination status of the community and to investigate the apparent measles vaccine failure. PMID- 1605770 TI - Pap smear taking in a general practice. Outcomes of a quality assurance audit. AB - Recent research suggests that population coverage of Papanicolaou smear taking in Australia has been inadequate. General practitioners have been encouraged to carry out audits of their own work in this field to improve both the quantity and quality of smears. The author outlines audit methods developed, and the results obtained in his practice. PMID- 1605771 TI - Gastroenteritis in children. PMID- 1605772 TI - Myocardial ischaemia. PMID- 1605773 TI - General practice research using computers. PMID- 1605774 TI - Congenital torticollis. PMID- 1605775 TI - Calcium antagonists and hypercalcaemia. PMID- 1605776 TI - An ICU links practice and theory through a journal club. PMID- 1605777 TI - The paediatric asthma management plan: a guide for nursing children with asthma. National Asthma Campaign of the Thoracic Society of Australia and New Zealand. PMID- 1605778 TI - Would you recognise Tourette syndrome? PMID- 1605779 TI - Euthanasia: a survey of nurses' attitudes and practices. PMID- 1605780 TI - ANF video causes controversy. PMID- 1605781 TI - HIV/AIDS and the nursing profession. PMID- 1605782 TI - Dantrolene. PMID- 1605783 TI - Recombinant tissue plasminogen activator (rt-PA). PMID- 1605785 TI - Union rationalization and Section 118A. PMID- 1605784 TI - Nurse and the law. Negligence in bizarre cases. PMID- 1605786 TI - Developments in diagnostic veterinary laboratory resources and competencies in Queensland. PMID- 1605787 TI - A lupinosis-associated myopathy in sheep and the effectiveness of treatments to prevent it. AB - A lupinosis-associated myopathy occurred in 26 of 48 sheep given a crude toxic extract of Phomopsis leptostromiformis, and in 18 of 34 sheep that grazed a toxic lupin stubble. Treatment with selenium or alpha-tocopherol alone neither prevented nor cured the myopathy, but selenium and alpha-tocopherol together may have been partially effective. Among the group of 48 intoxicated sheep, those with myopathy had a significantly lower mean terminal concentration of alpha tocopherol in their livers than those with no myopathy. There was no relationship between the severity of liver injury and the occurrence of the myopathy. It was considered that this lupinosis-associated myopathy may have a similar pathogenesis to nutritional myopathy. Data on plasma creatine phosphokinase and erythrocyte glutathione peroxidase activities, plasma alpha-tocopherol concentrations and terminal tissue concentrations of selenium and alpha tocopherol are presented. PMID- 1605788 TI - A serological survey to determine the prevalence of infection with Treponema hyodysenteriae in Western Australia. AB - A serological survey to detect antibody titres against Treponema hyodysenteriae was conducted on pigs from 106 herds in Western Australia. Titres indicating a positive result in the tests were determined by examining 400 sera from 4 herds known to be free of swine dysentery, and sera from immunised or experimentally infected pigs. Samples of serum from 40 bacon-weight pigs from each of the 106 herds were then collected at 2 abattoirs. Each serum was tested in enzyme-linked immunosorbent assays (ELISA) against the lipopolysaccharide of T hyodysenteriae of serogroups A, B and E, respectively. To assist in evaluating the test, 19 herds were resampled and retested, and faecal samples from 17 herds were cultured for T hyodysenteriae. Thirty-five of the 106 herds (33%) had serological evidence of infection when only one batch of sera from each herd was tested. The ELISA to detect T hyodysenteriae infection in herds using 40 sera was estimated as having a sensitivity of 77.3% and a specificity of 81.8% based on the owners' opinion of their herds disease status. Prevalence of infection within herds ranged from 2.5% to 47.5%, with a mean of 18%. PMID- 1605789 TI - Rhinocerebral and nasal zygomycosis in sheep caused by Conidiobolus incongruus. AB - The clinical findings, pathology and mycology of a cluster of 5 ovine cases of rhinocerebral and nasal zygomycosis caused by Conidiobolus incongruus are described. All cases were in Border Leicester or Merino x Border Leicester ewes from a flock pastured in a low-lying paddock adjoining a small tidal river in subtropical Queensland (latitude 28 degrees S). These cases of zygomycosis are believed to be the first infections due to C incongruus recorded in animals other than humans. The disease was subacute in 4 animals with a course of up to several weeks. In these, the primary site of infection was the posterior nasal cavity. The lesions extended to the dorsum of the face between the eyes, to the orbital cavity and to the anterior brain and meninges in the cranial cavity. In one animal, where the anterior nasal cavity was affected and iodine treatment used, the course was longer. The fungal granulomas had numerous foreign body giant cells, neutrophils and eosinophils. Fungal hyphae were thin walled, 6 to 8 microns in diameter, with occasional septa and irregular branching. They were cuffed with a wide zone of necrotic cell coagulum, or with homogeneous eosinophilic Splendore-Hoeppli granules. PMID- 1605790 TI - Screw-worm fly: an Australian perspective. PMID- 1605791 TI - Haematological reference values for alpacas. PMID- 1605792 TI - A comparison of sites for implanting identification transponders in cattle. PMID- 1605793 TI - Risk factors associated with the occurrence of swine dysentery in Western Australia: results of a postal survey. PMID- 1605794 TI - Cutaneous lymphosarcoma in a sugar glider. PMID- 1605795 TI - Hyperthermia in Merino wethers affected with humpyback disease. PMID- 1605796 TI - Efficacy of detection of oestrus in a dairy herd. PMID- 1605797 TI - [Synthesis and antineoplastic properties of anthracycline antibiotics modified by a sugar residue]. AB - The present review (for the previous part, see Bioorganicheskaya Khimia. 1990. V. 16. No 11. P. 1445-1464) describes the most important studies in the chemical modifications of the sugar moiety of anthracycline antibiotics and their analogues during last ten years. PMID- 1605798 TI - [The antigenic structure of ferritin. 1. Isolation of ferritin subunits and their immunochemical characteristics]. AB - A method for the isolation of monomers of ferritin subunits has been developed. The procedure comprises dissociation of ferritin by treatment with thioglycolic acid in the presence of phosphate ions and subsequent gel-permeation chromatography. Ferritin and a number of its structural analogues (apoferritin, carboxymethylated ferritin, H- and L-subunits of ferritin) have been immunochemically characterized. The immunoreactivity of ferritin is shown to vary along with the degree of denaturation. Isolation of monomers of H- and L-subunits results in appearance of new antigenic sites. These "hidden" antigenic determinants are presumed to be localized in the regions of intersubunit contacts and intracapsular surface of the ferritin molecule and are responsible for the differences in immunochemical properties of its H- and L-subunits. PMID- 1605799 TI - [Artificial DNA splicing using directed ligation]. AB - An approach to the directed genetic recombination in vitro has been devised, which allows for joining, in a predetermined chemical-enzymatic way, a series of DNA segments to give a precisely spliced polynucleotide sequence (DNA Splicing by Directed Ligation, SDL). The approach makes use of amplification, by several polymerase chain reactions (PCR), of the chosen DNA segments. The corresponding primers contain recognition sites of the class IIS restriction endonucleases, yielding protruding ends of unique primary structures. The protruding ends of the segments to be joined together are structurally predetermined to make them mutually complementary. Ligation of the mixture of the segments so synthesized gives the desired sequence in an unambiguous way. The suggested approach has been exemplified by the synthesis of a totally processed (intronless) gene encoding human mature interleukin-1 alpha. PMID- 1605800 TI - [Structure of carbohydrate chains of dimeric molecules and individual subunits of gonadotropin from the Russian sturgeon]. AB - Carbohydrate chains of gonadotropin from the Russian sturgeon hypophysis, as well as of alpha- and beta-subunits of the hormone, were split off and fractionated by gel-chromatography and HPLC. More than ten oligosaccharides released from the male and female hormones gave almost identical patterns, whereas differences between alpha- and beta-subunits were more noticeable. Basing on the chromatographic properties and monosaccharide compositions of the oligosaccharides isolated and the known structures of N-linked carbohydrates of mammalian hormones, the common carbohydrate chain of sturgeon gonadotropin is as follows: [formula: see text] Some oligomannosidic and/or hybrid chains and small oligosaccharides of the pentasaccharide core type were also found. Carbohydrate chains of fish gonadotropin have fewer sialic acid residues and significantly fewer (if any) sulphate groups than the mammalian hormones. PMID- 1605801 TI - [Conformational analysis of biologically active thyroliberin analogs by two dimensional NMR spectroscopy]. AB - Preferable conformations of thyrotropin-releasing hormone (TRH, Glp-His-Pro-NH2) and its analogues Glp-Glu(R)-Pro-NH2 (R = NHCH(CH3)CH2Ar), Glp-Gln-Abu-NH2, Dho Gln-Abu-NH2 in DMSO solution are determined using two-dimensional 1H NMR spectroscopy (delta-J-correlated, COSY and NOESY). Torsion angles psi i and chi i for every amino acid were calculated on the basis of the spin-spin coupling constants 3JNH-C alpha H and 3JC alpha H-C beta H values. The NOESY data were used for selecting the peptide conformations realized in solution. Distances between protons interacting by the dipole mechanism (d-contacts) were calculated using NOE values. These experiments allow one to estimate the torsion angles psi (between C alpha H-CO). TRH has an intramolecular H-bond between NH2-protons and His carbonyl with the torsion angles omega 3 = 180 degrees and psi 3 = 0 degrees. It is formation of this H-bond that apparently promotes the domination of the trans configuration of the His-Pro peptide bond. An intramolecular NH2-C alpha CO (Glp) H-bonding is revealed in other investigated compounds. It is known that a similar conformation of the TRH is realized in the course of its interaction with receptor. PMID- 1605802 TI - [Synthesis and antigenic activity of peptides of the nucleocapsid protein of the hepatitis delta virus]. AB - Hepatitis delta virus (HDV), a recently discovered infectious agent, participates in severe, often lethal forms of acute and chronic hepatitis and liver cirrhosis. Based on theoretical analysis of secondary structure, hydrophilicity and acrophilicity data, several regions of HDV antigen, presumably containing B epitopes, have been revealed and the corresponding peptides have been synthesized by the solid phase method. All the peptides obtained reacted with the respective antipeptide rabbit sera. The peptides and their conjugates with BSA or KLH were used for ELISA with individual and pooled anti-HD-positive sera from patients with chronic delta hepatitis. The high antigenicity of the peptide 65-80 shows that one of the antigenically active regions of HDAg is situated between these amino acid residues and that the peptide may be used for detection of anti-HD antibodies in patients blood sera. PMID- 1605803 TI - [Synthesis of spaced trisaccharides with blood group A and B specificity, their fragments, and structural analogs]. AB - Trisaccharides GalNAc alpha 1----3(Fuc alpha 1----2)Gal and Gal alpha 1----3(Fuc alpha 1----2)Gal, which are the determinant fragments of the human blood group specific antigens A and B, respectively, were synthesized as R-glycosides (R = beta-OCH2CH2CH2NHCOCF3). 4,6-BdGal-R was acetylated selectively at 3-OH, the 3-O acetate was alpha-fucosylated and then deacetylated to give a protected H disaccharide bearing a free 3-OH. The disaccharide was alpha-glycosylated with 2 azido-3,4,6-tri-O-acetyl-2-deoxy-beta-D-galactopyranosyl chloride (GCl) or 2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl bromide (GBr) to give protected spacered trisaccharides A and B, respectively. Disaccharides GalNAc alpha 1--- 3Gal-R and Gal alpha 1----3Gal-R were synthesized in two ways. 1. Hydrogenolysis followed by benzylidenation of Bzl3-2-O-Ac-Gal-R gave 4,6-Bd-2-O-Ac-Gal-R, which was alpha-glycosylated with GCl and GBr. 2. The required disaccharides were isolated from the mixture of di- and trisaccharides which was obtained by selective glycosylation of 4,6-Bd-Gal-R with GCl and GBr. Synthesis of GalNAc alpha 1----3(GalNAc alpha 1----2)Gal and Gal alpha 1----3(Gal alpha 1----2)Gal, non-natural analogues of A and B trisaccharides, is also described. Deprotected R glycosides were converted to OCH2CH2CH2NH2 (R1) derivatives, N-biotinyl derivatives were synthesized from GalNAc alpha 1----3(Fuc alpha 1----2)Gal-R1 and Gal alpha 1----3(Fuc alpha 1----2)Gal-R1 glycosides. The oligosaccharides, their macromolecular forms, and affinity sorbents obtained from them were used in the epitope specificity studies of the monoclonal antibodies and blood group typing. PMID- 1605804 TI - [Synthesis and various biochemical properties of alkylated derivatives of 2',3' dideoxy-3'-aminothymidine]. PMID- 1605805 TI - A novel class of platelet activating factor (PAF) antagonists. I. Synthesis and structure-activity studies on PAF-sulfonamide isosteres. AB - New platelet activating factor (PAF) antagonists, 3 were synthesized by replacing the charged phosphate and trimethylammonium moieties with sulfonamide and heterocyclic quaternary ammonium functionalities, respectively (PAF-sulfonamide isosteres). Darmstoff phosphatidic acid analogues of this class (Darmstoff sulfonamide isosteres), 6 were also synthesized. The activity of these compounds as PAF antagonists was evaluated from their in vitro inhibitory effect on PAF induced platelet aggregation in rabbit platelet-rich plasma. Among the compounds tested, some of the 2-methoxypropane derivatives with an octadecylcarbamoyloxy or octadecylcarbamoylthio side chain at the 1-position and a propylsulfonamide function bearing a terminal polar substituent such as a quaternary quinolinium or substituted quinolinium group at the 3-position were found to be the most potent (IC50 = 0.3-0.6 microM). PMID- 1605806 TI - Antithrombotic effects of a platelet fibrinogen receptor antagonist in a canine model of carotid artery thrombosis. AB - BACKGROUND AND PURPOSE: Platelet-fibrin thrombi in the lumen of atherostenotic carotid arteries may underlie transient ischemic attacks and cerebral infarction. For this reason, we investigated the antiplatelet and antithrombotic effects of a novel and potent platelet fibrinogen receptor (glycoprotein IIb/IIIa) antagonist (SK&F 106760). METHODS: The effects of 0.1-3.0 mg/kg i.v. SK&F 106760 on platelet aggregation were examined ex vivo in canine platelet-rich plasma (n = 20). In addition, the antithrombotic effects of SK&F 106760 were compared with those of aspirin in an acute canine model of extracranial carotid artery thrombosis with high-grade stenosis. Sham-operated (n = 4), vehicle-treated (n = 6), SK&F 106760 treated (n = 8), aspirin-treated (n = 9), and SK&F 106760+aspirin-treated (n = 5) dogs were examined. RESULTS: The intravenous administration of SK&F 106760 caused a dose-related inhibition of ex vivo platelet aggregation. In the carotid artery thrombosis model, an occlusive thrombus formed at stenotic sites in the region of the carotid bifurcation. The thrombogenic process caused a progressive reduction in carotid blood flow and reduced the cortical microvascular perfusion and electroencephalographic power. Based on nuclear magnetic resonance spectroscopy, the occlusive events depleted the stores of high-energy phosphates (adenosine triphosphate and phosphocreatine) and increased the lactate concentration in the forelimb somatosensory area of the parietal cortex. In this model, the administration of 1 mg/kg i.v. SK&F 106760 prevented thrombosis of the stenotic carotid artery. Consequently, neurophysiological, cerebral hemodynamic, and metabolic parameters were all improved significantly in the SK&F 106760-treated group. No dog receiving SK&F 106760 reoccluded during the 1-hour posttreatment observation period. In contrast, thrombosis of the carotid artery was associated with neurophysiological deterioration in six of the nine dogs treated with 5 mg/kg i.v. aspirin. Both spontaneous and evoked (increased carotid stenosis) aspirin-resistant thrombosis were abolished by SK&F 106760 treatment. CONCLUSIONS: These results suggest that antagonism of fibrinogen binding to platelet glycoprotein IIb/IIIa (the final common pathway for aggregation) may represent a new and more effective antithrombotic approach to the treatment of cerebral transient ischemic attacks and infarction associated with extracranial carotid artery disease. PMID- 1605807 TI - A test of the John Henryism hypothesis: cholesterol and blood pressure. AB - The personality predisposition "John Henryism" (JH) is a self-perception that one can meet demands of the environment through hard work and determination. The JH scale measures "efficacy of mental and physical vigor, commitment to hard work, and determination to reach one's goals." Previous research found an increased prevalence of hypertension among African-Americans with high JH scores and low socioeconomic status (SES). Six hundred fifty-three adult African-Americans in a church-based cardiovascular risk factor screening program completed the JH questionnaire. The prevalence of cholesterol greater than or equal to 240 mg/dl was highest (27%) among the high-JH/low-SES group when adjusted for age, sex, and body mass index. High JH/low SES was not associated with a greater prevalence of high blood pressure. Findings of this study suggest the need for additional research on John Henryism, socioeconomic factors, and cardiovascular risk among randomly selected samples of geographically and economically diverse African Americans. PMID- 1605808 TI - Why are experts not better in judging the danger of filmed traffic conflicts? AB - Earlier studies on the subject of subjective judgment of traffic conflicts showed that untrained subjects can reliably judge the dangerousness of filmed traffic conflicts. It was concluded that these judgements were based on a concept of dangerousness. In line with these findings two experiments were conducted. Experiment 1 tested the hypothesis that traffic experts (traffic engineers trained to evaluate and improve traffic safety) and lay people use the same concept of dangerousness when judging filmed conflicts. Experiment 2 investigated which aspects of the conflicts are considered by experts when making these judgements. The results show that (i) experts and lay people are equally reliable in judging traffic conflicts, (ii) experts base their judgement on the same concept of dangerousness, (iii) experts do not base their judgement on aspects that they themselves regard as important for the conflict, (iv) a weak relation is found between violations of traffic regulations and judgements of dangerousness. PMID- 1605809 TI - An examination of gender differences in traffic accident risk perception. AB - Excessively optimistic judgements of driving competency and accident risk have often been implicated in the disproportionate involvement of young males in traffic crashes. In this study, young male and female drivers (ages 18-24) were asked to judge their relative driving safety, skill, and accident likelihood. Comparisons were made using both peers and the average motorist as referent groups. Subjects then rated 15 risky driving behaviors on four dimensions: frequency in everyday driving, seriousness, accident potential, and apprehension likelihood. Self-report driving experience/history data were also collected. Substantial optimism was evident in both sexes, but males tended to be more optimistic, particularly when judging their driving skill. Males were equally optimistic with respect to the two referent groups; females tended to be less optimistic when making comparisons to the average motorist. Males and females held similar perceptions concerning the frequency and accident likelihood of the risky behaviors, but males perceived the behaviors as generally less serious and less likely to results in accidents. Regression analyses showed that considerably more variance in optimism could be explained for males than females. Driving record was the single best predictor of perceived safety; its role, however, was diminished for perceived skill and subjectively estimated accident likelihood. PMID- 1605810 TI - Occupant safety in modern passenger cars. AB - A study was undertaken recently for the Federal Office of Road Safety in Australia of 150 modern vehicle crashes where at least one of the vehicle occupants was admitted to hospital. The types of injuries sustained by occupants of modern Australian passenger cars involved in road crashes (including points of contact within the vehicle) were assessed to provide direction for future improvements in occupant protection. Seat belt performance in all seating positions was of particular interest. While the limited number of cases did not permit a full and detailed statistical analysis of these data, the findings nevertheless show there is scope for improving occupant protection for drivers and passengers of modern passenger cars. PMID- 1605811 TI - Industrial safety engineering--challenges of the future. AB - Safety management is now entering an era quite different to that which marked its foundation. The multiple challenges facing safety engineering are focused upon. In the United States, France, Britain, and Brazil, safety engineering has experienced fast growth over the past two decades. An increased questioning of the traditional assumptions of the profession in both traditional and postindustrial work has accompanied this growth. New directions of reflection and research are being pursued. Recent research in sociology, where worker perceptions of tasks and their dangers are incorporated into the analysis of accident production, brings promising but still incipient new perspectives to accident research and theory. Simultaneously, novel challenges for safety engineering are posed by the emergence of postindustrial technologies. Some of these threaten large civilian populations, and the knowledge is not currently available to guarantee accident prevention. In this way the responsibilities of safety engineering, both ethical and with regards the provision of information to the public, are brought under the spotlight. The face of safety engineering is being changed. PMID- 1605812 TI - The variation of drivers' accident rates between drivers and over time. AB - Accident records of individual drivers in eight large samples from the general driving population have been analysed as nonhomogeneous Poisson processes, i.e. by assuming that each driver's accidents occur randomly with an individual underlying accident rate that varies in time. Previous hypotheses about the form of this variation are reviewed. The moments of the distribution over drivers of individual underlying accident rates averaged over periods of one or more years are estimated; they indicate that most of the distributions are intermediate in form between the gamma and lognormal distributions. The results suggest the presence of an overall annual factor that multiplies all the individual rates; when this is removed the remaining process is approximately stationary (i.e. the mean and standard deviation are approximately constant in time). The coefficient of variation of individual accident rates falls slowly as the length of the period over which they are averaged increases, indicating positive correlation between the underlying accident rates of the same drivers in different periods. These correlations are estimated directly from the accident frequency data, which appears to be a new and useful method of analysis. For one sample, which spans 14 years, the correlation between two adjacent years is about 0.74 and falls approximately linearly to about 0.49 for two years separated by a gap of 12 years. A "switching process" with differing individual means, previously proposed for drivers' accidents by Bartlett, does not appear to fit these results well. A "scaling process," studied by Mandelbrot and previously found to apply in a number of different fields, provides a better fit to the data and could represent the combined effect of a hierarchy of switching processes operating on different time scales, in accordance with what is known or conjectured about the variation of factors affecting accident rates. Although the data analysed are affected by variation in exposure between drivers, the methods and ideas used have implications that may help to resolve the long-standing dispute about individual accident proneness. PMID- 1605813 TI - Restrained front seat car occupant fatalities--the nature and circumstances of their injuries. AB - The circumstances of a rural and urban sample of fatalities in vehicles less than six years old is described. The data originate from an in-depth, multidisciplinary study of accidents conducted in England since 1983. The sample is biased towards collisions that result in occupant injury, and this paper will concentrate on those accidents in which an occupant has been fatally injured. The initial police reporting of the fatalities included 11% of the deaths occurring from natural causes. Of the crash-related deaths with complete data, some 43% were frontal and lateral impacts, and they are analysed in greater detail. Thirty six percent of restrained occupants died in lateral collisions. In both frontal and lateral crashes, large amounts of intrusion result in direct loading of the head and chest, particularly. Under-run crashes with large trucks constitute 30% of frontal death cases, and only 12% of fatalities received fatal injuries from belt loads. Of those cases, additional loading by unrestrained rear passengers could have been an important feature. Multiplicity of severe injuries is the rule for restrained fatalities, with head injuries as the most common cause of death. Eighty-two percent died within an hour of their crashes. Some consequences for vehicle compatibility in crashes are discussed. PMID- 1605814 TI - Older driver population and crash involvement trends, 1974-1988. AB - North Carolina motor vehicle crash data for even-numbered years 1974-1988, inclusive, are analyzed in conjunction with North Carolina population, licensed driver, and mileage data to examine trends in motor vehicle crash involvement by driver age, sex, and race. Crash rates per licensed driver are presented along with crash rates per estimated vehicle miles travelled calculated on the basis of induced exposure. Results focus particularly on older drivers. They show that older drivers' representation in the licensed driver population has increased at a greater rate than their representation in either the census or crash involvement populations. These trends are particularly strong for females and for nonwhites. Furthermore, crash rates have declined more for drivers aged 55 and older than for younger drivers. The greatest declines, both in terms of crashes per licensed driver and crashes per estimated miles travelled, have been experienced by drivers age 65 and older, particularly nonwhites. Males show higher overall crash rates per miles travelled than females, but this effect decreases with age and disappears entirely in the oldest age categories. Results are discussed in light of the changing nature of the overall driving population and the cohort of older drivers in particular. PMID- 1605815 TI - Are radar detector users less safe than nonusers? AB - One hundred and seventy-four drivers who had purchased special insurance coverage during 1988-1989 for in-vehicle equipment that included a radar detector were compared to a similarly sized and sociodemographically stratified driver population random sample. It was found that the radar detector owners had significantly more accident claims and speeding convictions during the period 1986-1989 than those representing the general driver population. PMID- 1605816 TI - Alcohol and fatal road accidents: estimates of risk in Australia 1983. AB - This paper concerns the statistical relationship between the risk of a fatality and the age and sobriety of drivers in New South Wales, Australia. The estimation of this relationship is based on fatal accident data from New South Wales and non accident or control data from South Australia collected between the hours of 5.00 AM and 3.00 PM. The results are presented in new ways. In particular, tables of "accidents attributable to alcohol" and age specific intensity functions of "risk attributable to alcohol" may be an aid to policy making. PMID- 1605818 TI - Estimating the traffic safety effect of studded tires. AB - Swedish accident and exposure data from December 1989 to February 1990 are used to estimate the risk of involvement in an accident on a slippery road when using studded tires compared with the risk when driving with summer tires. Two methods have been used, one involving both accident and exposure data, the other using only accident data. Both methods give similar estimates, indicating that studded tires reduce the risk of involvement in slippery road accidents by 20%-50%. PMID- 1605817 TI - Comparison of motor vehicle occupant injuries in restrained and unrestrained 4- to 14-year-olds. AB - This study compares injuries of restrained and unrestrained 4- to 14-year-olds in nine emergency rooms and the Coroner's office in Orange County, California from 1983 to 1989. Analyses were performed separately for 4- to 9- and 10- to 14-year olds because of differences related to the fit of the seat belt. Significantly fewer intracranial injuries and a significantly lower mean Injury Severity Score (ISS) were seen between the restrained and unrestrained for 10- to 14-year-olds in the front passenger and back seats; but for 4- to 9-year-olds in the back seat only. These same differences were noted between restrained 4- to 9-year-olds in the back compared with those in the front passenger seat. Except for 4- to 9-year olds in the front passenger seat, our findings are consistent with similar studies of occupants of all ages. Our results suggest that lap-shoulder belts (primary restraint in front seat) may provide less protection for 4- to 9-year olds than for 10- to 14-year-olds and adults. PMID- 1605819 TI - Travel exposure and choice of comparison crashes for examining motorcycle conspicuity by analysis of crash data. AB - Much research has been conducted examining the problem of motorcycle road crashes. Most of this research has concluded that motorcyclists have a conspicuity problem, particularly during the day. This type of research has often involved comparing multi-vehicle motorcycle crashes with single vehicle motorcycle crashes occurring during the day and night. The aim of this paper is to point out that comparison of single and multiple vehicle motorcycle crashes juxtaposes subsets of crashes with clearly different causes (car drivers' possible failure to detect a motorcyclist against motorcyclists' loss of vehicle control). Comparing groups of crashes for which conspicuity can be posited as a common cause (car drivers' possible failure to detect a motorcyclist or car) may be a more enlightening comparison. The issue of exposure is also examined in this paper. PMID- 1605820 TI - Increasing safety belt use in a secondary enforcement state: evaluation of a three-county special enforcement program. AB - Special enforcement programs to increase belt use present a unique challenge in states with secondary enforcement laws. This paper reports findings from an evaluation of a combined public information and education/enforcement program to increase restraint use along a highly traveled corridor in three Michigan counties. This program (US-31 SAVE) was successful in increasing belt use at least temporarily along the special enforcement corridor. Observed belt use increased from a baseline rate of 56.7% to 65.1% during the program before slipping slightly to 62.7% after the intensive enforcement and PI&E declined (all differences significant at p less than .05). This paper details program and evaluation activities and suggests future research needs to better understand the most effective mix of public information and enforcement efforts in states with secondary belt use laws. PMID- 1605821 TI - Helmet use, patterns of injury, medical outcome, and costs among motorcycle drivers in Maryland. AB - A comprehensive study was conducted of all motorcycle traffic crashes occurring in Maryland during a one-year period. All available medical and cost data were linked with police crash reports. During the study period, 1,900 motorcycle drivers were involved in crashes. The data indicated that (i) helmet usage was 35% overall, 30% among fatally injured drivers, and only 16% among drivers with a history of drug/alcohol conviction, (ii) unhelmeted drivers seen at an emergency department were almost twice as likely to have sustained head injury (40%) as were helmeted drivers (21%) (the corresponding percentages for hospitalized drivers were 55% and 38%), and (iii) acute care cost for unhelmeted drivers was three times ($30,365) that of helmeted drivers. PMID- 1605822 TI - A comparison of some statistical techniques for road accident analysis. AB - At the TRRL/SWOV Workshop on Accident Analysis Methodology, held in Amsterdam in 1988, the need to establish a methodology for the analysis of road accidents was firmly stated by all participants. Data from different countries cannot be compared because there is no agreement on research methodology, data collection, and analysis. Linear and log-linear models are regularly used for the analysis of such data. This paper discusses the background of these models and the model assumptions. It is stated that two relevant and fundamentally different classes of models exist. However, in most cases the difference between these classes remains implicit. These classes of models are called design oriented and object oriented models. Within the context of linear models, the basic assumptions deal with this distinction and the generalization of linear to log-linear models. It is argued that there are advantages and disadvantages for each choice and that a check on the tenability of a particular model is to be recommended. Two different types of generalized linear models, both object-oriented, are used by SWOV and TRRL for the analysis of accidents of road users or on particular road locations. The qualitative data analysis (QDA) models used at SWOV are primarily descriptive and useful for model exploration. The generalized linear interactive modeling (GLIM) technique used at TRRL has stricter assumptions, but is better suited for model testing. In order to compare these models, a number of analyses has been carried out on roundabout data from TRRL. The outcomes are consistent and highly comparable. The results show that for this kind of data these two types of models are to be preferred over classical multiple linear regression analysis (MLR) and log-linear analysis of contingency tables (LLA). QDA turned out to be the most powerful in data exploration. A QDA analysis showed that the dominant accident type of entering and circulating accidents had a different relation with the road and traffic characteristics of the roundabouts than the other accident types and should be analyzed separately. Furthermore, it was shown by a QDA analysis that the choice of a log-link function was preferable over an identity relation as used in MLR. This log-link function in combination with the choice of a Poisson error distribution results in a GLIM model with parameter estimates and errorbounds for these estimates. The errorbounds can be used as an indication of the reliability of the parameters. It is stated that the combination of QDA and GLIM is most powerful for the analysis of this type of problems. PMID- 1605823 TI - Driver behaviour at horizontal curves: risk compensation and the margin of safety. AB - A study involving unobtrusive observation of drivers at horizontal curves before and after realignment is described. The speeds and path radii adopted by drivers in the curves before and after realignment are compared, as are the levels of side friction demanded by each driver while negotiating the curves before and after realignment. The results reveal substantial variations between drivers (with respect to speed, path radius, and side friction demand) and between the path and curve radii. While vehicle speeds increased markedly, the side friction demand was reduced for all curves except one. It is concluded that the margin of safety was increased for all curves, and this is supported by the accident data. PMID- 1605824 TI - The effectiveness of Unna Boot and semipermeable film vs. Unna Boot alone in the healing of venous ulcers. A pilot report. PMID- 1605825 TI - Innovative technologies for the treatment of urinary incontinence. PMID- 1605826 TI - Effects of high voltage galvanic stimulation on wound healing. PMID- 1605827 TI - Achieving a state of urinary continence for residents of nursing facilities. Part III: Manufactured incontinence. AB - The recognition and treatment of manufactured incontinence requires a thorough understanding of the pathogenesis of urinary incontinence. It is important to realize that is frequently not only what is done to the patient but what is not done or even what is overlooked. PMID- 1605828 TI - Bowel control interventions: nurses can make a difference. Part I: Identification of the problem. PMID- 1605829 TI - Reading right: an exercise in critique. AB - The previous critique of the "mini-article" merely scratches the surface with respect to critical reading of the literature. However, it is of vital importance to know whether the authors' conclusions are substantiated by the results obtained. Therefore, do not be intimidated by the data; pull out your calculator, verify the numbers, and practice your critical reading skills. After all, practice makes perfect! PMID- 1605830 TI - Writing for journal publications. How to write case reports. PMID- 1605831 TI - Healthcare reform '92. PMID- 1605832 TI - Chemistry and biology of boron. AB - Boron is an essential nutrient for certain organisms, notably vascular plants and diatoms. Cyanobacteria require boron for formation of nitrogen-fixing heterocysts and boron may be beneficial to animals. Boron deficiency in plants produces manifold symptoms: many functions have been postulated. Deficiency symptoms first appear at growing points, within hours in root tips and within minutes or seconds in pollen tube tips, and are characterized by cell wall abnormalities. Boron deficient tissues are brittle or fragile, while plants grown on high boron levels may have unusually flexible or resilient tissues. Borate forms cyclic diesters with appropriate diols or polyols. The most stable are formed with cis-diols on a furanoid ring. Two compounds have this structure physiologically: ribose in ribonucleotides and RNA, and apiose in the plant cell wall. Germanium can substitute for boron in carrot cell cultures. Both boron and germanium are localized primarily in the cell wall. We postulate that borate-apiofuranose ester cross-links are the auxin-sensitive acid-growth link in vascular plants, that the cyanobacterial heterocyst envelope depends on borate cross-linking of mannopyranose and/or galactopyranose residues in a polysaccharide-lipid environment, and that boron in diatoms forms ester cross-links in the polysaccharide cell wall matrix rather than boron-silicon interactions. Complexing of ribonucleotides is probably a factor in boron toxicity. PMID- 1605833 TI - The mode of action of lipid-soluble antioxidants in biological membranes: relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles. AB - The effects of ubiquinol and vitamin E on ascorbate- and ADP-Fe3+-induced lipid peroxidation were investigated by measuring oxygen consumption and malondialdehyde formation in beef heart submitochondrial particles. In the native particles, lipid peroxidation showed an initial lag phase, which was prolonged by increasing concentrations of ascorbate. Lipid peroxidation in these particles was almost completely inhibited by conditions leading to a reduction of endogenous ubiquinone, such as the addition of succinate or NADH in the presence of antimycin. Lyophilization of the particles followed by three or four consecutive extractions with pentane resulted in a complete removal of vitamin E and a virtually complete removal of ubiquinone, as revealed by reversed-phase high pressure liquid chromatography. In these particles, lipid peroxidation showed no significant lag phase and was not inhibited by either increasing concentrations of ascorbate or conditions leading to ubiquinone reduction. Treatment of the particles with a pentane solution of vitamin E (alpha-tocopherol) restored the lag phase and its prolongation by increasing ascorbate concentrations. Treatment of the extracted particles with pentane containing ubiquinone-10 resulted in a restoration of the inhibition of lipid peroxidation by succinate or NADH in the presence of antimycin, but not the initial lag phase or its prolongation by increasing concentrations of ascorbate. Malonate and rotenone, which prevent the reduction of ubiquinone by succinate and NADH, respectively, abolished, as expected, the inhibition of the initiation of lipid peroxidation in both native and ubiquinone-10-supplemented particles. Reincorporation of both vitamin E and ubiquinone-10 restored both effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605834 TI - 5-Formyl-5,6,7,8-tetrahydromethanopterin is the intermediate in the process of methanogenesis in Methanosarcina barkeri. AB - Formylmethanofuran:tetrahydromethanopterin (H4MPT) formyltransferase and 5,10 methenyl-H4MPT cyclohydrolase purified from Methanosarcina barkeri catalyze a formyl group transfer and the hydrolysis of the methenyl function, respectively. The results from UV spectroscopy and HPLC analyses, and comparison with results obtained with the enzymes isolated from Methanobacterium thermoautotrophicum showed 5-formyl-H4MPT to be the product of the formyltransferase and cyclohydrolase reactions in M. barkeri. The findings disagree with an earlier report in which 10-formyl-H4MPT was identified as the product of the cyclohydrolase in the latter organism. In addition, it was observed that 10 formyl-H4MPT, which is non-enzymically formed from 5,10-methenyl-H4MPT at alkaline pH, becomes rapidly converted into the 5-formyl derivative. The latter finding explains why the nature of the formyl species previously had been improperly assigned. PMID- 1605835 TI - Synthesis of a new organic pyrophosphate in large quantities is induced in some bacteria by oxidative stress. AB - Brevibacterium ammoniagenes and Micrococcus luteus were shown to synthesize up to 50 mM of a novel substance, 2-methylbutan-1,2,3,4-tetraol 2,4-cyclopyrophosphate, in response to oxidative stress created by benzyl viologen and other redox mediators under aerobic conditions. The substance, which represents greater than 50% of the extractable phosphorus, is suggested to play a role as a bacterial antistressor and is thought to be a product of condensation of two molecules of phosphoenolpyruvate whose accumulation is prompted by conversion of intracellular NADPH into an oxidized form. PMID- 1605836 TI - Variations in S-adenosylmethionine, S-adenosylhomocysteine and adenosine concentrations in rat liver. AB - The hepatic concentrations of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and adenosine (Ado) in the rat were examined diurnally and as a function of fasting. Ado concentrations increased continuously throughout the fasting period; concentrations after 2 days of fasting were 7.5-fold higher than control values. Diurnally, the concentration of Ado was highest during the light hours. SAM and the ratio of SAM/SAH were reduced greater than 50% due to fasting and exhibited a significant daily rhythm which appeared to be related to dietary methionine availability. Hepatic SAM concentrations decreased continuously during the light hours and increased during the dark period to levels 7.3-fold greater than the lowest light values. The concentration of SAH was altered in a similar fashion yet to a much lesser degree such that the ratio of SAM/SAH paralleled the changes in the concentration of SAM. The SAM/SAH ratio exhibited a 4.5-fold difference between the peak and nadir values. PMID- 1605837 TI - The possible mechanism of binding interaction of insulin molecule with its receptor. AB - Detailed structural comparisons and investigation of DPI, 2 Zn insulin and some other derivatives of insulin were performed by the least-squares superimposition technique and the graphics technique. It is pointed out in this paper that the binding interaction with the receptor molecule should take place mainly on an amphipathic surface of the insulin molecule. In the middle, there is a hydrophobic surface with an area of about 150 A2 consisting of many hydrophobic residues; while the polar or charged groups distributing around the hydrophobic surface construct a hydrophilic zone. The hydrophobic surface is usually covered by the extended B-chain C-terminal peptides with great mobility and protected from the solvent molecules. The angle between the amphipathic surface and the surface of dimerization is about 20 degrees. The results from the detailed structural comparison between Al-(L-Trp) insulin and Al-(D-Trp) insulin have provided a very good explanation to their great difference in biological activity, and confirmed our proposed binding interaction model of the insulin molecule with its receptor as well. PMID- 1605838 TI - Variations of lectin-binding glycoproteins in early pregnant rabbit embryo. AB - In the present study, the quantitative and qualitative changes of three kinds of lectin-binding glycoproteins of early pregnant rabbit embryos (D4-D12) were analyzed. The technique of Western blot, as well as video densitometer scanning and its analytic software was used for analysis. Results found that there were five specific lectin-binding glycoproteins in Day 4 to Day 6 blastocyst fluids: one ConA-binding glycoprotein about 70 kD, two WGA-binding glycoproteins respectively about 42 kD and 25 kD and two PNA-binding glycoprotein respectively about 180 kD and 75 kD. They disappeared immediately after implantation. It is demonstrated that there are stage-specific glycoproteins in rabbit blastocyst fluid which might be relevant to the recognition of pregnancy and implantation. PMID- 1605839 TI - Working toward creating a baby friendly hospital. PMID- 1605840 TI - Lubrication enhances latch on. PMID- 1605841 TI - Relactation and "high needs" infants". PMID- 1605842 TI - ASPO/Carnation alliance. PMID- 1605843 TI - The association of formula samples given at hospital discharge with the early duration of breastfeeding. AB - Conflicting results have been reported regarding the association of formula samples given at hospital discharge with breastfeeding duration. This study investigated the relationship between the distribution of formula samples and breastfeeding duration in low-income Hispanic women. A gift pack of formula was distributed randomly to 88 breastfeeding women. All women received a telephone call at one and three weeks to collect information about infant feeding. Chi square analysis revealed no significant difference in the proportion of women exclusively breastfeeding at one week. However, fewer women were exclusively breastfeeding in the gift pack group at three weeks (p less than .004). Gift packs given to Hispanic breastfeeding women are associated with a decrease in exclusively breastfeeding during the first three weeks postpartum. PMID- 1605844 TI - Social support and lactation outcomes in postpartum women. AB - Questionnaires were mailed to 45 primiparous lactating women at six weeks postpartum to measure their perceived social support and its influence on lactation outcomes. Also evaluated were the size and structures of their support networks. Subjects were asked to share their thoughts and feelings regarding breastfeeding. There were no statistically significant differences between perceived support scores of women who considered themselves successful or those women who felt unsuccessful in their lactation experience. There was a significant correlation between numbers of health care provider support, informational support and perception of successful lactation. Thematic analysis identified differences in personality characteristics and focus of breastfeeding concerns. Increasing a woman's informational support network to include qualified health care professionals may increase the numbers of women who are satisfied with their breastfeeding experience. PMID- 1605845 TI - The Mother-Baby Assessment (MBA): an "Apgar score" for breastfeeding. AB - Communication about breastfeeding among health workers is hampered by the lack of a standardized method of documentation for breastfeeding. Scoring methods previously described by Matthews, Jenks, and Bocar and Shrago focus on the baby's behavior. I am proposing a "Mother-Baby Assessment (MBA) Score," a ten-point assessment of maternal and infant breastfeeding behavior. The assessment system may be used to track the progress of a mother-baby pair as they learn how to breastfeed, and also may be useful in hospital charting, when making referrals, when practicing triage, or when conducting research. PMID- 1605846 TI - Ineffective suckling: a possible consequence of obstructive positioning. AB - Failure to thrive in breastfed babies frequently is attributed to inadequate lactation. In some cases, the origin of inadequate lactation may be ineffective suckling that obstructs milk flow. To support this conclusion, an infant who presented with failure to thrive was studied at the breast with magnetic resonance imaging. PMID- 1605848 TI - Human milk storage and preservation in the early 1900s. PMID- 1605847 TI - Perinatal medications and breastfeeding. PMID- 1605849 TI - The household guide or domestic cyclopedia, home remedies for man and beast. 1894. PMID- 1605851 TI - The cDNA sequence of the human pro-hormone and pro-protein convertase PC1. AB - Using a probe consisting of the full-length cDNA sequence of the mouse pro hormone convertase PC1 (mPC1), we isolated from a lambda gt10 human pituitary cDNA library a number of contiguous clones, of which composite sequence of 3.3-kb defined the complete coding sequence of human PC1 (hPC1). The cDNA sequence of hPC1 encodes a protein containing 753 amino acids and potentially two N glycosylation sites, one carboxy-terminal amidation site, a cAMP-dependent protein kinase Ser phosphorylation site, a tyrosine kinase phosphorylation site, and an ArgGlyAsp (RGD) sequence. Like mPC1, the carboxy-terminal sequence of hPC1 exhibits an amphipathic domain potentially involved in membrane association. The coding region of hPC1 exhibits an overall 92.6% protein sequence identity to the mouse mPC1 sequence, with the highest homology (98%) found in the catalytic segment of the molecule (residues 84-399). Whereas Northern blot analysis of tissues obtained from mouse, rat and porcine demonstrated the presence of two mRNAs of 3 kb and 5 kb, Northern blots of human tissues and cells demonstrated the presence of a dominant transcript of 6.2 kb and the presence of smaller transcripts in some tissues. The major site of production of hPC1 seems to be the pituitary and brain, although detection was also possible in pancreas and heart. PMID- 1605850 TI - Dioxin induces expression of c-fos and c-jun proto-oncogenes and a large increase in transcription factor AP-1. AB - Among environmental pollutants, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; dioxin) is one of the most potent tumor promoters and teratogens known. The molecular mechanisms responsible for the biological activity of TCDD, however, remain largely unknown. In this report, we show that the first observable effects of TCDD in cultured murine hepatoma cells are a rapid, transient increase in Ca2+ influx and a minor but significant elevation of activated, membrane-bound protein kinase C. These changes are then followed by induction of the immediate early proto-oncogenes c-fos, jun-B, c-jun, and jun-D, and by large increases in AP-1 transcription factor activity. Induction of these changes by TCDD is delayed compared with that by phorbol esters, although the magnitude of the effects caused by both treatments is similar, and both induction processes can be blocked by staurosporine, a protein kinase C inhibitor. In cultured cells, proto-oncogene induction by TCDD appears to be independent of the presence of a functional aryl hydrocarbon (Ah) receptor or nuclear translocation protein. These results reveal early events that may lead to the elucidation of the molecular basis of TCDD induced tumor promotion. PMID- 1605852 TI - Regulation of LDL receptor, apoB, and apoE protein and mRNA in Hep G2 cells. AB - The regulation of low-density lipoprotein (LDL) receptor activity, protein synthesis, and cellular mRNA content was evaluated in the human hepatoma cell line Hep G2. Incubation of the cells with LDL led to a complete downregulation of LDL receptor mRNA and LDL receptor protein synthesis. This LDL regulation of the LDL receptor and its mRNA was both time- and concentration-dependent. In contrast to protein synthesis and cellular mRNA concentrations of the LDL receptor, which were reduced to undetectable levels by prolonged incubation in the presence of LDL, LDL receptor activity was reduced to only 44% of preincubation levels. These findings support the presence of a second metabolic pathway for LDL uptake in human hepatocytic cells. The effect of LDL on cellular LDL receptor expression was specific for LDL because incubation in the presence of HDL did not affect any of these study end points. The potential coordinate regulation of the expression of the LDL receptor with its principal ligands, apolipoproteins (apo) B and E, was also investigated. In contrast to the LDL receptor mRNA downregulation with LDL incubation, cellular apoB and apoE mRNA concentrations were not affected by either LDL or HDL. Secretion of apoB, however, was significantly increased by incubating Hep G2 cells with LDL. These findings indicate that, in contrast to LDL receptor which is regulated at the mRNA level, the ligands for the LDL receptor are regulated either co- or post-translationally. PMID- 1605853 TI - Functional analysis of the rat insulin-like growth factor I gene and identification of an IGF-I gene promoter. AB - Insulin-like growth factor I (IGF-I) mediates many of the systemic growth promoting effects of growth hormone and also functions as a locally acting growth stimulator. In mammals, IGF-I gene expression is complicated, as the gene is transcribed and processed into multiple mRNAs (ranging in length from less than 1 to nearly 7.5 kb) that encode at least two protein precursors. As a step toward understanding the regulation of IGF-I, we report the complete organization of the rat IGF-I gene, including identification of the structural determinants for all IGF-I mRNA species, and an initial functional analysis of its promoters. The gene is composed of 6 exons distributed over nearly 80 kb of chromosomal DNA and is structurally heterogeneous. Several transcription start sites were identified within IGF-I exons 1 and 2, adjacent to presumptive promoters 1 and 2, respectively, and at least three polyadenylation sites were mapped to exon 6. To test promoter function, fusion genes were constructed linking fragments of IGF-I DNA to a reporter plasmid. Chimeric genes containing at least 395 bp of DNA from the 5'-flanking region of exon 1 enhanced luciferase activity after transfection into the IGF-I-producing SK-N-MC cell line, while fusion plasmids containing up to 1,300 bp of DNA from the 5'-flanking region of exon 2 were inactive. Relative levels of IGF-I mRNAs containing exons 1 or 2 varied among different rat tissues, although in response to acute or chronic growth hormone treatment both classes of transcripts were induced coordinately in rat liver. These observations represent the first thorough characterization of a mammalian IGF-I gene, and provide a starting point for defining the mechanisms by which growth hormone and other trophic factors regulate IGF-I gene expression. PMID- 1605855 TI - Characterization of the clathrin heavy chain from Dictyostelium discoideum. AB - We report the cloning and analysis of a clathrin heavy-chain cDNA from the eukaryotic microorganism, Dictyostelium discoideum. A single gene, designated chcA, for the clathrin heavy chain encoded a protein of 1,694 amino acids with a molecular mass of 193,618 daltons. Comparison of the amino acid sequence with the rat and with the yeast sequence showed that the highly conserved protein was more similar to the mammalian clathrin heavy chain (57% identity) than to the yeast heavy chain (45% identity). The mRNA for the clathrin heavy chain was regulated during development. mRNA levels were highest during vegetative growth and declined as the cells progressed through the 24-hr developmental cycle. The concentration of clathrin heavy-chain protein was the same in cells grown in liquid media (high rates of pinocytosis) as in cells grown with bacteria (low rates of pinocytosis), which suggests that regulation of pinocytosis in these cells is not achieved by altering the concentration of clathrin. PMID- 1605854 TI - Structure and expression of mouse alpha 1-acid glycoprotein gene-3 (AGP-3). AB - The genome of Mus domesticus has multiple genes of the alpha 1-acid glycoprotein (AGP). Two cDNA clones were identified corresponding to AGP-1 and AGP-2. Moreover, two alleles of AGP-1 exist in inbred mice. The genomic DNA of the AGP-2 gene has been cloned and studied. Here we report the genomic organization of three M. domesticus AGP genes, the sequence analysis of the AGP-3 genomic DNA, and the expression of the AGP-3 gene. The major structural differences between AGP-2 and AGP-3 genes are located in introns 1 and 5. The low level of AGP-3 mRNA can be detected by the polymerase chain reaction (PCR). The molecular basis of the low level expression of AGP-3 and the possible classification of AGP-3 as a pseudogene are discussed. PMID- 1605856 TI - Determination of the chromosomal size of three different strains of Enterococcus faecalis and one strain of Enterococcus faecium. AB - Pulsed-field gel electrophoresis was used to determine the chromosomal size of three different strains of Enterococcus faecalis and one strain of Enterococcus faecium. The size determinations of OG1X, a strain of E. faecalis widely used in many laboratories for genetic studies, using Sma I, Not I, and Sfi I alone or in combination, ranged from 2,750 to 2,761 kb. Using the same enzymes as with OG1X, the size of HH-67, a plasmid-free clinical isolate of E. faecalis, was determined to be 2,170-2,288 kb and the size of JH2-2, an E. faecalis recipient strain, ranged from 2,008 to 2,135 kb. The size range generated for GE-1, a plasmid-free E. faecium strain, with the use of Sma I, Not I, and Apa I was 2,045-2,155 kb. Although OG1X differed in size from the other three enterococci, each individual enterococcal strain generated reproducible results in different experiments. However, for both E. faecalis OG1X and E. faecium GE-1, one of the enzymes used generated a considerably smaller molecular size than that generated by the other two enzymes. The discrepancy was due to visually undiscernible comigrating fragments, and serves to point out a potential source of error if fewer than two enzymes are used to size a genome. The size discrepancies were resolved by digesting individual fragments with a second enzyme. The molecular sizes of these enterococcal strains are larger than that recently reported for Campylobacter, smaller than that of Escherichia coli and Pseudomonas aeruginosa, and similar (OG1X) or smaller (JH2-2, HH67, and GE-1) than the 2,819-kb reported for Streptococcus mutans. PMID- 1605857 TI - Multiplex random priming of internal restriction fragments for DNA sequencing. AB - An approach for DNA sequencing is described that circumvents the need for synthetic oligonucleotide primers, which seriously restrict the progress of DNA sequencing in the commonly used protocol. The method is based on the use of short restriction fragments as primers randomly distributed along single-stranded templates. Premapping of target DNA is eliminated and subcloning manipulation is minimized. This method has been used successfully for sequencing genes in the range of 2 kb, for which about 10 restriction fragment primers per kilobase were sufficient to generate a continuous overlapping sequence in alignment. The approach has also been readily applied for an automated sequencing system with the fluorescent chain-terminating dideoxynucleotides, thus implying its potential for sequencing large genomic DNAs. PMID- 1605858 TI - Tissue-specific expression of kallikrein family transgenes in mice and rats. AB - To define the regulatory strategy for the transcriptional control of the kallikrein multigene family, we analyzed the expression of several kallikrein/SV40 T-antigen (TAg) fusion genes in transgenic mice and rats. Kallikrein family members are normally expressed at a high level in the submandibular gland and are expressed in a wide range of tissues that vary among individual family members. A total of 1.7 kb of proximal 5'-flanking DNA from the tissue kallikrein gene (rKlk1) was sufficient to confer much of the correct tissue-specific pattern on a TAg reporter gene. TAg mRNA was detectable in tissues that normally express rKlk1 and TAg-induced tumors arose in brain and pancreas. However, absolute levels of transgene mRNA were very low relative to the expression of the normal endogenous tissue kallikrein gene. In particular, expression in the salivary glands, normally very high for endogenous rKlk1, was either low or absent. An intact rKlk1 transgene with extensive flanking DNA (4.5 kb 5' and 4.7 kb 3') and complete intragenic (4 kb) sequences was expressed similarly to the fusion transgene, demonstrating that regulatory elements necessary for comprehensively correct expression are not contained within these additional gene regions. Two additional kallikrein/SV40 fusion transgenes were derived from other family members, one from the rKlk2 gene, which encodes tonin, and another from the rKlk8 gene, which encodes a prostate kallikrein. Whereas the endogenous rKlk2 and rKlk8 genes normally are expressed at high levels in rat salivary glands, they were not expressed in the salivary glands as transgenes. The results for these transgenes of three different family members indicate that control elements that direct the particular nonsalivary gland expression pattern characteristic of each family member may be present within the proximal 5' flanking region of each gene, whereas regulatory sequences necessary for normal levels of expression in these tissues and for maximal salivary gland expression are not. We propose that the gene-associated regulatory sequences are complemented by a dominant control region that imposes salivary gland expression on the extended kallikrein family locus. PMID- 1605859 TI - Identification of molecular defects causing congenital adrenal hyperplasia by cloning and differential hybridization of polymerase chain reaction-amplified 21 hydroxylase (CYP21) genes. AB - Congenital adrenal hyperplasia (CAH), one of the most common autosomal recessive disorders, is caused primarily by defects in the gene encoding steroid 21 hydroxylase, CYP21B. The molecular diagnosis of CAH, important for prenatal diagnosis, carrier detection, and a better understanding of the various clinical CAH forms, is complicated by the close proximity of a highly similar pseudogene, CYP21A, containing (and probably donating, by gene conversion-like events) most of the defects underlying CAH. In this study, we describe an efficient strategy to identify molecular defects causing CAH: polymerase chain reaction-amplified CYP21 loci are cloned and hybridized to a set of oligonucleotides, allowing rapid and allele-specific identification of all known CYP21B mutations relevant to 21 hydroxylase function. Possible new mutations can be identified by subsequent nucleic acid sequencing provided they reside within the cloned CYP21B fragment (from the TATA box to the 8th of the 10 CYP21B gene exons). Using this method, the CYP21B gene mutations of a heterozygous carrier and 25 CAH patients have been identified by oligonucleotide hybridization. All disease haplotypes seem to have been generated by recombinational events involving the CYP21A pseudogene. In 5 individuals, these data were subsequently verified by nucleic acid sequencing. The procedure can be used for diagnostic applications and may facilitate identification of new CYP21B defects. PMID- 1605860 TI - Demethylation of specific sites in the 5'-flanking region of the CYP17 genes when bovine adrenocortical cells are placed in culture. AB - DNA methylation of CYP17 (steroid 17 alpha-hydroxylase) was studied in bovine adrenocortical cells, which lose the capacity to express this tissue-specific gene in culture by phenotypic switching. Restriction enzyme digestions, and sequencing of a lambda clone of a second CYP17 gene (CYP17A2), showed that there are at least three CYP17 genes in the bovine genome. Southern blotting of DNA digested with Msp I or Hpa II together with Eco RI was used to investigate the methylation status of Hpa II sites at -1.0 kb (H1), -1.8 kb (H2), and -2.3 kb (H4) in CYP17A1 and CYP17A2 and at -0.7 kb (H0) in CYP17A3. In cells and tissues other than white blood cells, H0 was nonmethylated whereas H1 was always methylated; H2 and H4 showed variation in methylation status among different cells and tissues. In particular, whereas H4 was methylated in the bovine adrenal cortex in vivo, there was a rapid and complete demethylation at H4 when adrenocortical cells were placed in culture. Sites downstream from H4 did not change methylation over the first six passages in culture; additionally, the coding region of CYP17 remained fully methylated under all conditions. In contrast to adrenocortical cells, DNA from fibroblasts was nonmethylated at H2, whereas all downstream sites were fully methylated. Digestion with another methylation-sensitive enzyme, Bsa HI, which has a site between H2 and H4, showed that this region is methylated in intact adrenal cortex but nonmethylated both in cultured adrenocortical cells and in fibroblasts. The specific changes in methylation at this site and at H4 in adrenocortical cells indicate a reproducible, environmentally determined change in methylation in adrenocortical cells when they are placed in culture. PMID- 1605862 TI - The expression of murine protein disulfide isomerase in Escherichia coli. AB - Protein disulfide isomerase (PDI), a luminal enzyme of the endoplasmic reticulum (ER), is thought to be involved in the process that assures that the correct disulfide bonds form as a newly synthesized protein folds into its appropriate three-dimensional structure (Freeman, 1984). In recent years, the ER has been shown to have at least two additional, distinct PDI-related luminal proteins (Bennett et al., 1988; Mazzarella et al., 1990). As a potential first step toward an investigation of the structure and function of PDI and of the PDI-related proteins as well, we have developed a bacterial expression system in Escherichia coli capable of synthesizing significant levels of enzymatically active PDI under the control of the inducible tac promoter. We have observed that the use of this bacterial expression system is complicated by the fact that there is a significant amount of internal initiation of protein synthesis within the PDI coding sequence and the fact that all of the PDI-related expression products are found equally distributed between the cytoplasmic and periplasmic fractions due to a single peptide-independent mechanism. Our studies with this system have demonstrated that at least some truncated PDI molecules containing the carboxy terminal most active site have significant PDI activity. PMID- 1605861 TI - Molecular analysis of a cytochrome P450 gene of family 4 on the Drosophila X chromosome. AB - A member of the cytochrome P450 superfamily has been identified within region 2D of the Drosophila X chromosome. The sequence of this gene shows strongest homology with P450 family 4 genes, and has thus been named CYP4D1 in accordance with convention. This P450 gene is expressed throughout Drosophila development, with the highest levels of transcript accumulation occurring during late larval stages. A fragment of Drosophila genomic DNA including the CYP4D1 gene has been reintroduced into the germ line by P-element-mediated transformation. This transduced fragment does not rescue any of the lethal mutations that have been identified in this genetically well-characterized region of the Drosophila genome. PMID- 1605863 TI - [We are using...]. PMID- 1605864 TI - [302 days--Werner update. 7]. PMID- 1605865 TI - [Brinkgreven in Deventer--5 jaar VS (nursing staff)]. PMID- 1605866 TI - [First pharmaceutical trade fair in The Netherlands. Also for nurses]. PMID- 1605867 TI - [SOVOV (Foundation for the Support of Renewal in Education for the Nursing and Caring Professions), or professional practice as starting point. "After 2 or 3 years you think: I can do something different'. Interview by Toine de Graaf]. PMID- 1605868 TI - [Nutrition for psychiatry. The inner person in psychiatry]. PMID- 1605869 TI - ['You can draw many parallels between Orem and Roy'. Interview by Toine de Graaf]. PMID- 1605870 TI - [Orem in nursing of mentally retarded]. PMID- 1605871 TI - [Immunization in hospitalized children: alternative vaccination strategies]. PMID- 1605872 TI - [Immunizations in hospitalized and outpatient children: the reduction of lost vaccination opportunities]. AB - Among the strategies directed towards the control of preventable illnesses through vaccination, are the "National Days for Vaccination" and the intensive campaigns for country-wide vaccination, which have been taking place in our country during the last few years. An important aspect that must be taken into account is the immunization of children or patients who are hospitalized or those are under medical supervision due to changing chronic pathologies which have is some way interfered with the normal course of the application of the basic scheme of immunizations. The causes which have lead to incomplete vaccination schemes or to unstarted ones have been analyzed in different studies. In many cases, it has been observed that the information available to parents as well as to health workers in inexact. Hospitalization per se does not constitute a contraindication for vaccination, except in certain circumstances where there is some relation to the type of vaccine, as for example that of live attenuated virus or the existence of an underlying disease, like neoplasms and congenital or acquired immunodeficiency, which should be individually studied to evaluate the application of the vaccine depending on each individual case. PMID- 1605873 TI - [Factors influencing the immunization of children in the outpatient clinic of a pediatric hospital]. AB - In 1991 a study conducted at the Hospital Infantil de Mexico in Mexico City, as a project of the MCH IPHI Program at the Center for Population and Family Health, Columbia University, New York. The purpose was to investigate health professional's knowledge, perceptions of barriers and actions to promote immunization. Knowledge, perceptions of barriers and actions (KPA) surveys were administered to 101 residents and 104 nurses. Using SPSS/PC analysis of health professionals (KPA) surveys demonstrate no correlation between their knowledge, perceptions of barriers to immunization and actions undertaken (P greater than 0.05). Recommendations made to the Hospital Infantil de Mexico include: the review of the immunization card on a regular basis, health education programs on immunization at the community and health professionals level, and interpersonal and mass communication. PMID- 1605874 TI - [Scurvy. A study of 13 cases]. AB - Scurvy or vitamin C deficiency disease it is seen nowadays with a very low frequency. Thirteen cases in which scurvy was diagnosed at Hospital del Nino "Rodolfo Nieto Padron" at Villahermosa, Tabasco, Mexico, in a 5 years period (from March 1985 through May 1990) were reviewed. The cases occurred in infants between 5 and 18 months. All of them had a third grade malnutrition and also had a concomitant infectious disease. Pain localized on extremities was the most important symptom. Anemia was seen in all cases. Roentgenologic studies showed the presence of Fraenkel line, scurvy lattice and subperiostitic calcifications in all cases; these changes are characteristic of scurvy. The chief complaint, physical findings, radiologic signs and the response to treatment with ascorbic acid will give the clue to make diagnosis. The present report shows the incidence of scurvy in the southeast of the Mexican Republic. We are aware about this disease as a great health problem even nowadays which needs the responsibility of all those who care for infants to assist educational aspects mainly in urban areas. PMID- 1605875 TI - [Trichinosis in children. A report of 8 cases]. AB - A comparative study between 8 cases of trichinosis and 16 of typhoid fever is presented in this paper; all of them were attended in the INP during the period from 1970 to 1990. The diagnosis was established under epidemiologic, clinic and laboratory bases. The range of age of these patients was from 10 to 14 years, from low socioeconomic status; half of the cases had history of in take of infested pork meat. The most characteristic symptoms were: fever, myalgia and limitation of muscular movements. Leukocytosis in addition to eosinophilia were found in 7 cases. Correlation with indirect hemagglutination, CIEF positive test for Trichinella spiralis and biopsy of muscle was done. Thiabendozole therapy was utilized for treatment with satisfactory evolution, except in one case that developed progressive and fatal neurologic damage. PMID- 1605876 TI - [Diaphragmatic eventration. Our experience with 50 cases]. AB - Diaphragmatic eventration is the abnormal elevation of the diaphragm as a result of paralysis, aplasia or atrophia of the muscular fibers. This is a diagnostic problem specially in the newborn. The objective of this report is present the clinical course and surgical management of 50 cases attended in the Hospital Infantil de Mexico Federico Gomez. Of them, 56% were males; eight were newborns; five with previous surgery. The clinical course was variable; the landmark was the chest X-ray findings. There were operated 36 cases. The right diaphragm was the most frequent affected; the surgical management was with thoracotomy in the great majority of them. In 30 cases had good evolution two years after surgery. PMID- 1605878 TI - [The pediatrician and the oral health of children. A survey of 100 pediatricians]. AB - The pediatrician plays a very important role assisting the dental profession for the education of the parents to prevent oral disease and maintain children's oral health. This study shows the results obtained in a survey with 100 pediatricians from different institutions and universities of Mexico, in order to analyze their knowledge on basic dental care. The results will be utilized to prepare a guide that will show to pediatricians the basic concepts that parents should know about prevention of caries, malocclusions, and the teaching of correct oral habits from early years for their children. PMID- 1605877 TI - [Pneumopathy in children with juvenile rheumatoid arthritis]. AB - In the National Institute of Pediatric were studied 35 patients with juvenile rheumatoid arthritis, in a prospective form, in order to asses pulmonary manifestations. Arthritis had between 5 months to five years of clinical evolution. The radiologic patterns of the lung correlated well with respiratory tests, without correlation with pulmonary gammagram which was normal in all the cases. Symptoms were not characteristic of any type of pulmonary lesion. PMID- 1605879 TI - [Chromosomal translocation (2;13) in disseminated rhabdomyosarcoma]. AB - A 12-year-old male with a disseminated alveolar rhabdomyosarcoma is reported. The diagnosis was difficult because of the clinical manifestations and the histological patterns of the bone marrow and a chest wall tumor. Diagnosis was confirmed through the histologic picture of a gum biopsy and the karyotype of the tumoral cells of the bone marrow. Chromosome study revealed a hypotetraploid cell line with the translocation (2;13) characteristic of this type of neoplasias. The usefulness of chromosome studies in solid tumors of childhood is emphasized. PMID- 1605880 TI - [Carcinoma of the tonsils in pediatrics]. AB - Tonsillar malignancies are frequently diagnosed as peritonsillar cellulitis or abscess until the tumor's growth is evident. The suspicion must arise when there is persistent and asymmetric tonsillar growth without fever. The presence of affected regional lymph nodes is of bad prognosis. A pediatric case is discussed, and recent reports are reviewed. PMID- 1605881 TI - [Adverse reactions to drugs in pediatric medicine. A point of view]. AB - The ever growing volume of medical literature on adverse drug reactions in pediatric medicine and the lack of a thorough pharmacological screening of drugs in children, deserve particular attention from clinicians. A word of caution is given to keep adverse drugs reactions into perspective and a word of advise is also given to encourage clinicians to report adverse drug reactions in children. Various aspects of this old and yet actual problem are given pointing out new examples as introductory remarks to forthcoming reviews. PMID- 1605882 TI - Alcohol reduces the number of pheochromocytoma (PC12) cells in culture. AB - Pheochromocytoma (PC12) cells were used as an in vitro neuronal cell model to examine detrimental effects of alcohol on cell numbers. Alcohol exposure (100, 200, 400, and 800 mg/dl) reduced PC12 cell numbers in a dose-dependent manner. Cells that were treated with nerve growth factor (NGF) incurred less severe reductions in numbers compared with cells that were never treated with NGF. Because NGF stops proliferation of many of the PC12 cells and differentiates them into neuronal-like cells, these data suggest that differentiated, nonproliferating cells are less vulnerable to alcohol-induced reductions in cell numbers. In a subsequent experiment using only undifferentiated PC12 cells, alcohol reduced cell number of both proliferating and nonproliferating cultures; however, the reductions in proliferating cultures were more severe than in nonproliferating cultures. Two mechanisms may account for alcohol-induced reductions of PC12 cell numbers--inhibition of proliferation and killing of cells. PC12 cell cultures are a useful model system to examine mechanism(s) underlying alcohol's depletion of neuronal-like cells. PMID- 1605883 TI - Locomotor activity but not conditioned place preference is differentially affected by a moderate dose of ethanol administered to P and NP rats. AB - The conditioned place preference (CPP) test and spontaneous motor activity were used in order to determine if ethanol-preferring (P) rats differ from ethanol nonpreferring (NP) rats after the administration of a moderate (1.0 g/kg) dose of ethanol. Results indicate that both of the selectively bred lines of rats found ethanol aversive, with little difference between the P and the NP rats. In contrast, the NP rats were shown to be more sensitive to the motor-impairing effect of ethanol. PMID- 1605884 TI - Breath acetaldehyde following ethanol consumption. AB - Five pairs of volunteers were studied to determine the effect of drinking ethanol on breath acetaldehyde levels. On a given study day, samples of breath were obtained for measurement of acetaldehyde and ethanol from both participants at t = -1 h, t = -0.5 h, and at t = 0 to obtain baseline values. The drinkers were then given ethanol (0.3 g/kg body weight), and the controls given an equal volume of tap water. Breath samples were then taken at 0.5, 1, 1.5, 2 h, and hourly until t = 6 h. The last sample taken was at t = 23.5 h. Acetaldehyde levels in breath were quantified with a fluorigenic high-performance liquid chromatographic assay. Blood ethanol was approximated using a breath analyzer. Acetaldehyde in breath rose 50-fold at the 0.5-h, time point and returned to levels not significantly different from baseline values by 3-4 h. The mean peak blood ethanol values reached 0.055%. The t 1/2 elimination for ethanol was 1.6 h, and that for acetaldehyde was 2.25 h. Elimination of both acetaldehyde and ethanol in breath were initially 0 order. A significant correlation (r = 0.74) was found between baseline breath acetaldehyde levels and peak acetaldehyde levels. We conclude that acetaldehyde resulting from ethanol intake rapidly partitions into breath. The correlation of baseline breath acetaldehyde values with peak values found after an ethanol challenge indicate that measurement of breath acetaldehyde may be useful in the identification of individual differences in ethanol metabolism. PMID- 1605885 TI - Effects of Ro 15-4513 and ethanol on operant behavior of male and female C57BL/6 mice. AB - Although the partial benzodiazepine receptor inverse agonist, Ro 15-4513, counteracts many ethanol effects, its effect on operant behavior or on ethanol induced changes in this behavior, remains controversial. In this study, we examined the effects of Ro 15-4513, ethanol, and their interaction on behavior maintained by an FR 20 schedule of food reinforcement. Ro 15-4513 (1.0-4.0 mg/kg) and ethanol (1.5-3.0 g/kg) reduced lever-responding of both male and female mice. The disruptive effect of Ro 15-4513 was of short duration (approximately 10 min), and was greater in male than in female mice. Under equivalent dose and time parameters, ethanol disrupted behavior of both sexes to the same extent. In spite of the disruptive effects of both drugs when given alone, when given after ethanol and prior to testing, Ro 15-4513 attenuated the disruptive effects of ethanol in male mice. The present study extends previous reports by documenting: (1) that the disruptive effect of Ro 15-4513 on mice is of very short duration and occurs at lower doses than previously reported; (2) that, in spite of being disruptive itself, Ro 15-4513 can attenuate the disruptive effects of ethanol on schedule controlled behavior; and (3) that gender is an important consideration in determining the effects of this compound. PMID- 1605886 TI - Diazepam- and chlordiazepoxide-mediated increases in erythrocyte aldehyde dehydrogenase activity and its possible implications. AB - Erythrocyte ALDH activity was assayed in alcoholic (n = 70) and nonalcoholic (n = 40) subjects. In general, alcoholics without any prior medications (n = 57) were found to have a decreased ALDH activity (mean +/- SD: 3.38 +/- 1.7 mU; p less than 0.001) as compared to control group (5.10 +/- 1.57 mU). However, a group of alcoholics who were detoxified with benzodiazepines (n = 13) prior to blood collection for enzyme assay were found to have higher ALDH activity (4.92 +/- 2.46 mU; p less than 0.05) as compared to alcoholics who were not detoxified. In vitro experiments demonstrated that both diazepam (DZM) and chlordiazepoxide (CDP) could activate the ALDH. The magnitude of enzyme activation by DZM and CDP appear to correlate with their relative potency of tranquilizing effect. Further, the observed ability of DZM to reverse the inhibition of ALDH mediated by disulfiram may explain the biochemical basis of the reported ability of benzodiazepines (BDZ) to reduce the intensity of disulfiram ethanol reaction (DER). PMID- 1605887 TI - The relationship between saccharin and alcohol intake in rats. AB - Male rats were given daily sessions during which a palatable saccharin solution was available. Based on intakes averaged over 3 days, groups with low, intermediate, or high intake of saccharin were formed. These rats were then given daily sessions in which alcohol (2-8%) or water were available. Initially, sessions were conducted with rats on a food restriction schedule; in later sessions, food was available ad lib. When rats were food restricted, there were no differences among the groups in terms of alcohol or water intake. When the food restriction schedule was discontinued, alcohol intake in the intermediate and high saccharin intake groups was generally higher than that of the low saccharin group. On the final series of alcohol sessions, the high saccharin group consumed significantly more 2% and 6% alcohol than the low saccharin group. These results are consistent with reports which have found that rats selected for high or low alcohol intake have corresponding high and low intakes of saccharin. PMID- 1605888 TI - Ethanol-induced motor activity in normal and acatalasemic mice. AB - The role of brain catalase in modulating the psychopharmacological effects of ethanol was investigated by examining ethanol induced motor activity in normal, C3H-N, and a corresponding group of acatalasemic C3H-A, mice. Following administration of one of three doses of ethanol (0.8, 1.6, and 3.2 g/kg) or saline, mice were placed in open field chambers and locomotor and rearing activity was measured during a 10-min testing period. A significant increase in locomotor activity was recorded in both groups of mice at lower doses of ethanol, while the higher dose produced a marked depression. Normal mice demonstrated more locomotor activity than acatalasemic mice at all ethanol doses. No differences between both groups of mice were observed in rearing activity. Also, no differences in blood ethanol levels were observed between the two substrains. Brain and liver residual catalase activity in the acatalasemic mice was found to be 40% and 50%, respectively, of normal mice. Furthermore, evidence for possible involvement of the peroxidatic activity in ethanol-induced motor activity is presented. These results suggest a role for centrally formed acetaldehyde as a factor mediating some of ethanol's psychopharmacological effects. PMID- 1605889 TI - Ethanol elimination among different racial groups. AB - This study examined the relationship between ethanol elimination and race, specifically exploring differences among Alaskan Natives, American Indians, and whites. Native Americans, believed to be of recent Asian origin, were expected to eliminate alcohol faster than whites. The data suggested that both Native American men and women eliminated alcohol faster than whites. A relationship was also found between age, gender, and rate of alcohol elimination. The implications of these findings were reviewed and specific needs for future research were noted. PMID- 1605890 TI - Prenatal ethanol effects: sex differences in offspring stress responsiveness. AB - Previous studies have shown that offspring prenatally exposed to ethanol are hyperresponsive to stressors in adulthood, and have suggested that females are typically more affected than males. The present study was undertaken to investigate further this apparent sex difference in prenatal ethanol effects on stress responsiveness. Male and female offspring from prenatal ethanol-exposed (E), pair-fed (PF), and ad lib-fed control (C) conditions were tested in adulthood to determine adrenocortical responses to a prolonged (4-h) restraint stress. There were no significant differences in corticoid responsiveness among females from the three treatment groups. All females showed a marked increase in plasma corticosterone at 30 min, and corticoid levels remained elevated through 150-min restraint. By 180 min, all females showed a significant corticoid decrease, although corticosterone remained elevated over basal levels throughout the 240-min stress period. For males, in contrast, there were significant differences among groups. All males showed a significant corticoid increase over basal levels at 30 min, and corticoids remained significantly elevated through 90 min restraint. By 120 min, PF and C males showed a significant corticoid decrease although corticoids never returned to basal levels during the 240-min restraint period. E males, however, showed no significant decrease from peak corticosterone levels throughout the 240-min restraint stress. These data indicate that pituitary-adrenal hyperresponsiveness is not limited to fetal ethanol-exposed females, but may be demonstrated in fetal ethanol-exposed males under appropriate conditions.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605891 TI - Biochemical changes and essential metals concentration in lead-intoxicated rats pre-exposed to ethanol. AB - The effects of chronic lead exposure on some hematopoietic and hepatic biochemical indices and urine, feces, and tissue essential metal concentration were investigated in rats pre-exposed to different doses of ethanol. Exposure to ethanol (0.5, 1.0, and 2.0 g/kg intraperitoneally, once daily) for 4 weeks produced an inhibition of blood delta-aminolevulinic acid dehydratase (ALAD) activity and a decrease in hepatic glutathione (GSH) concentration. Ethanol ingestion also produced a dose-dependent elevation of hepatic lipid peroxidation. Blood and hepatic calcium and hepatic magnesium contents decreased and urinary Ca and fecal Ca and Mg contents increased significantly following 4-week exposure to ethanol (2 g/kg). Lead administration (10 mg/kg, orally) for 4 weeks in ethanol pre-exposed (2 g/kg) animals produced a more pronounced inhibition of blood ALAD and elevation of urinary delta-aminolevulinic acid (ALA) excretion and hepatic GSH contents. Hepatic GSH contents decreased and hepatic lipid peroxidation increased significantly in rats given lead and pre-exposed to ethanol (2 g/kg). A more pronounced depletion of blood Ca and Mg and hepatic Mg was observed along with significant elevation of urinary Mg and fecal Ca excretion in animals administered lead and pre-exposed to ethanol (2 g/kg). The results suggest that nutritional deficiencies, particularly depletion of body Ca and Mg levels, play an important role in increasing susceptibility to lead intoxication in the rat. PMID- 1605892 TI - Olfactory loss in alcoholics: correlations with cortical and subcortical MRI indices. AB - The relationship between olfactory identification ability and MRI volumetric indices of specific cortical and subcortical brain regions was investigated in 36 recently detoxified male alcoholics. The results of correlational analyses between MRI indices and score on the University of Pennsylvania Smell Identification Test (UPSIT) revealed that impairment in olfactory identification was associated with elevated cortical and ventricular CSF volumes as well as with reduced tissue volumes in the cortical and subcortical grey matter. The volume of the thalamus was found to be a significant unique predictor of UPSIT score, even after accounting for variance shared with other MRI indices. These findings provide the first empirical support for existing hypotheses that olfactory loss in alcoholic subjects may be mediated by both cortical and subcortical structures. PMID- 1605893 TI - Gender differences in the effects of ethanol on C57BL/6 mice. AB - The influence of gender on the stimulatory and depressant effects of ethanol was examined in C57BL/6 (C57) mice. In Experiment 1, locomotor activity was assessed in young (2-month-old) male and female mice injected intraperitoneally (IP) with stimulatory (1.5 g/kg) or depressant (2.5 g/kg) doses of ethanol. Both the stimulatory and the depressive effects of ethanol were greater in young male than female C57 mice, and the gender difference was unrelated to blood ethanol concentration (BEC). In Experiment 2, older (9-month-old) male and female mice were given ethanol (2.5 g/kg) either by IP injection or gavage to determine if the gender differences in BEC and ethanol effects observed in the first experiment depended upon the route of ethanol administration. In this experiment, ethanol reduced locomotor activity more in males than females whether given by gavage or IP injection, and the males had higher BECs than females at the time of testing. Thus, the differences in the behavioral effects of ethanol appeared to be related to BEC. The greater depressive effect of ethanol on older male mice in this experiment is consistent with an earlier report of prolonged ethanol hypnosis in older male C57 mice. Therefore, differences in BEC could account for the gender differences in the behavioral effects of ethanol on older but not young mice. The gender difference in BEC of mice obtained in the present and earlier reports is opposite to that reported for humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605894 TI - Terminal vessels of dentate gyrus in chronically alcohol-intoxicated rats. AB - Quantitative changes in the microvasculature of the central nervous system of the rat following chronic ethanol intoxication were studied. For 6 months, 12 rats drank only 25% ethanol and eight control rats only water. After fixation by perfusion, semithin sections of dentate gyrus were obtained. In each one, semiautomatic measurements were made of the length, surface, and volume densities, and the mean area of a terminal vessel cross-section and the results were evaluated statistically. Chronic ethanol intoxication caused an increase in the length and surface density, a decrease in the mean cross-sectional area, whereas the volume density of terminal vessels was unchanged. These results show that the reduction of the mean surface area of terminal vessels after prolonged ethanol intoxication is compensated by the increase of other morphometrically measurable parameters, i.e., length and surface density. As a consequence of these alterations, the volume density remains unchanged. The results indicate great reactivity of the microvascular system of the dentate gyrus in chronically ethanol-intoxicated rats. PMID- 1605895 TI - Effects of ethanol injection to the preoptic area on sleep and temperature in rats. AB - Bilateral microinjection of ethanol to the preoptic area of rats causes a dose dependent hypnotic effect at doses that do not affect brain temperature. Rats were polygraphically recorded for 6 h, and brain temperature was recorded every 10 min for 3 h. Administration of 0.047 mumol ethanol increased total sleep during the 3-6 h interval, while 0.24 and 0.47 mumol ethanol increased deep slow wave sleep (SWS2) and total sleep during the 3-6- and 0-6-h intervals. The 0.24 mumol ethanol microinjections also increased REM sleep for the 0-6-h interval. No changes in sleep latencies were observed. PMID- 1605896 TI - The effects of acute ethanol on growth in rat liver: steady state c-myc transcripts. AB - In order to elucidate the effects of acute ethanol on compensatory liver growth (regeneration), the steady state c-myc mRNA levels were studied following two thirds partial hepatectomy. After surgery, control rat livers exhibited two peaks of c-myc transcripts, at 0.5-2 h and at 8-10 h. Sham surgery did not induce c-myc mRNA expression. Ethanol (3 g/kg), administered by gavage at 1 hour prehepatectomy, had no effect on the initial peak of c-myc mRNA; however, the second peak was eliminated. Control gavage of isocaloric glucose prior to partial hepatectomy had no effects on either of the subsequent c-myc mRNA peaks. Blood alcohol levels were found to be elevated throughout the prereplicative phase. These results suggest that ethanol may disrupt proto-oncogene expression near the restriction point at the G1/S boundary of the cell cycle in hepatocytes. PMID- 1605897 TI - Prescribing short-acting hypnosedatives. Current recommendations from a safety perspective. AB - The duration of action of hypnosedative drugs is mainly determined by their pharmacokinetic properties. The ideal drug should induce sleep within 30 min and maintain a normal pattern of sleep for 6 to 8h, with little or no residual effects the next morning. Clinically, 4 types of insomnia can be distinguished: prolonged latency, 1 to 2 long periods of wakefulness, frequent short awakenings and early morning awakening. An ultra-short-acting drug (2 to 3h), such as triazolam, is useful for prolonged latency. Temazepam, lormetazepam and loprazolam provide more prolonged effects (8 to 10h). These benzodiazepines are not free of daytime adverse effects, particularly drowsiness, dependency potential, rebound insomnia and habituation to the drug effect. Zopiclone and zolpidem are new nonbenzodiazepine hypnotics that are as effective as benzodiazepines but without the problems associated with the latter. They produce a more normal electroencephalogram sleep pattern and so would seem to approach to the ideal hypnosedative for the future. However only further clinical trials and widespread use in practice will determine whether they will live up to this potential. PMID- 1605900 TI - Effects of estazolam and flurazepam on cardiopulmonary function in patients with chronic obstructive pulmonary disease. AB - Benzodiazepine drugs have been shown to suppress respiratory function in patients with chronic obstructive pulmonary disease (COPD). We designed a placebo controlled crossover study to compare the effects of a new benzodiazepine, estazolam ('ProSom'), with those of flurazepam ('Dalmane') on cardiopulmonary function in COPD patients. 29 patients completed all treatment phases (estazolam 2 mg, flurazepam 30 mg or placebo). Respiratory and cardiovascular function were assessed in awake patients on days 1 and 5 (acute and cumulative effects). Eight patients were also assessed during sleep in each period. The effects of estazolam and flurazepam on ventilatory response to CO2 and mouth occlusion pressure were no different from those of placebo. However, acute administration of flurazepam lowered tidal volume and increased inspiratory flow. Although no clinical signs of respiratory depression were observed with any long term treatment, flurazepam decreased oxygen saturation and inspiratory time and increased respiratory frequency. Neither drug altered breathing control during sleep. Our results indicate that estazolam 2 mg is equally as safe a hypnotic agent as flurazepam for patients with mild COPD. PMID- 1605901 TI - Life-threatening hyperkalaemia in an elderly patient receiving captopril, furosemide (frusemide) and potassium supplements. AB - An elderly patient with congestive heart failure developed serious hyperkalaemia and reversible nonoliguric renal failure during combined therapy with captopril, furosemide (frusemide) and potassium supplements. This case illustrates that such complications can occur late during the course of treatment with angiotensin converting enzyme (ACE) inhibitors. It is therefore important that both the renal function and plasma potassium are closely monitored in such patients even if these parameters are normal at the beginning of therapy. PMID- 1605899 TI - Age-related differences in digoxin toxicity and its treatment. AB - Digoxin toxicity remains a common medical problem for both adults and children. In addition to a vastly improved understanding of the mechanisms for digoxin action on the heart, there are now data which clearly demonstrate that there are potentially important developmental differences in both the pharmacodynamics and pharmacokinetics of digoxin which have a direct impact on its efficacy and toxicity profile. The developmental pharmacokinetics of the drug have been extensively studied such that profiles for age-dependent differences in the apparent volume of distribution, plasma and renal clearance and elimination half life now exist. It is these data which have also produced the current age specific dosing guidelines for the therapeutic administration of digoxin in various paediatric subpopulations. Despite this new knowledge, both accidental and iatrogenic digoxin toxicity still occurs in paediatric patients, with potentially life-threatening arrhythmias being produced when steady-state serum digoxin concentrations exceed 5.1 nmol/L. Consequently, the clinician may be faced with the decision to use antidotal therapy with digoxin-specific Fab fragments (d-Fab). This article reviews the developmental basis for digoxin disposition and its pharmacological and toxic effects. Additionally, the treatment of acute digoxin toxicity in children is reviewed, especially as pertains to the therapeutic use of d-Fab. PMID- 1605902 TI - Spontaneous fractures in a patient treated with low doses of etidronic acid (disodium etidronate). AB - The recommended regimen of etidronic acid (disodium etidronate) for the treatment of Paget's disease of bone is 5mg/kg/day for a period of less than six months. There have, however, been reports of impaired mineralisation of bone and concern that the risk of fracture is increased with this dosage. We report a patient with Paget's disease in whom fractures occurred through pagetic and non-pagetic bone which appeared to be causally related to treatment with lose doses of etidronic acid. The osteomalacia resolved when etidronic acid was discontinued. PMID- 1605905 TI - Hematopoietic stem cells. AB - Recent studies indicate that hematopoietic stem cells that provide long-term reconstitution can be separated from more mature hematopoietic cells that provide radioprotection and short-term repopulation. With these findings it is now possible to design assays that will specifically measure long-term repopulating stem cells, as well as to develop culture systems that can be used to analyze the effects of known and putative novel cytokines on their growth and differentiation. PMID- 1605903 TI - Oral retinoids. What should the prescriber known about their teratogenic hazards among women of child-bearing potential? PMID- 1605898 TI - Thalidomide in human immunodeficiency virus (HIV) patients. A review of safety considerations. AB - The sedative thalidomide was withdrawn from the market 30 years ago because of its teratogenic and neurotoxic adverse effects. The compound was later discovered to be extremely effective in the treatment of erythema nodosum leprosum, a complication of lepromatous leprosy. This effect is probably due to a direct influence on the immune system, because thalidomide possesses no antibacterial activity. The compound is presently used as an experimental drug in the treatment of a variety of diseases with an autoimmune character, including recurrent aphthosis of nonviral and nonfungal origin in human immunodeficiency virus (HIV) patients. This article reviews the most important chemical and pharmacokinetic properties of thalidomide. The possible mechanisms of the nonsedative effects of thalidomide with respect to the safety of its use in HIV patients are discussed. Because the mechanism of the immunomodulatory effect of thalidomide is unknown, the possibility that the administration of this compound will accelerate the deterioration of the immunological status of HIV patients cannot be excluded. Clinical evidence suggests that thalidomide may aggravate the condition of patients with preexisting peripheral neuropathy. Hypersensitivity reactions to thalidomide may occur more frequently in HIV patients than in other patient groups. Because of the teratogenic activity of thalidomide, reliable contraception must be provided to female patients of childbearing age. Before the introduction of thalidomide therapy to an HIV patient presenting with oral ulcers, a fungal or viral origin of the lesions should be excluded. Thalidomide should not be used in patients with preexisting HIV-related peripheral polyneuropathy, polyradiculopathy or encephalopathy. In patients experiencing a complete remission, the discontinuation of thalidomide treatment and its reintroduction in the case of a relapse are preferable to maintenance therapy. PMID- 1605906 TI - Early and late B-cell development in the mouse. AB - A common principle in B-cell development is the stringent selection of cells expressing appropriate antibody V regions as surface receptors. Cells failing to do so appear destined to rapid death. These life-death decisions are mediated by signals whose nature is not yet understood but whose generation involves immunoglobulin receptor complexes on B cells and B-cell progenitors. PMID- 1605907 TI - Early B-cell development in chickens, sheep and rabbits. AB - Studies of the immune system of various species have revealed that antibody repertoire can be generated in many different ways. This review underlines some general principles for comparing the different processes which represent the basic framework of these systems. PMID- 1605908 TI - Embryonic stem cells and homologous recombination. AB - Mice with defined genetic defects can now be generated using gene targeting technology based on the successful generation of mouse embryonic stem cells with the potential for germ line transmission, and the development of methods for detection of homologous recombination. PMID- 1605904 TI - Gastroprotection and nonsteroidal anti-inflammatory drugs (NSAIDS). Rationale and clinical implications. AB - There is no doubt that nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal injury. The most serious consequences are gastric and duodenal ulcers which can cause bleeding and perforation, and which may lead to the premature death of 3000 to 4000 patients in the UK annually. The immediate actions of NSAIDs operate at a subcellular level; in particular altering of mitochondrial function which causes depletion of ATP and renders the cell vulnerable to oxidant stress. Secondary consequences follow, such as the inhibition of prostaglandin synthesis which delays cellular repair. While adaptation can be shown in volunteers despite continued NSAID ingestion, studies in patients suggest mucosal damage develops continuously and cumulatively even with low doses of aspirin. Histamine H2-receptor antagonists and proton pump inhibitors heal NSAID-related ulcers, though healing rates with H2-antagonists are slower in patients who continue NSAID treatment. They have little role in preventing damage. In addition to acid suppression, prostaglandin analogues cause bicarbonate secretion and enhance mucosal blood flow. They have a specific role in both prevention and treatment of NSAID-related damage. The use of misoprostol offers a rational approach to reduce the high prevalence of unwanted gastroduodenal damage from NSAIDs. On a purely financial basis more information is needed before routine coprescribing can be recommended. However, for any patient on NSAIDs with a previous ulcer or for patients aged over 60 years (where the risks and seriousness of complications are markedly increased), the use of misoprostol should be considered. Further developments in prostaglandin analogues may reduce their adverse effects and perhaps thereby improve their efficacy at symptom control. PMID- 1605909 TI - Analysis of lymphocyte activation and metabolism by flow cytometry. AB - The use of flow cytometry for the study of lymphocyte activation and cellular metabolism continues to expand. This has permitted rapid progress in the understanding of the regulation of multiple intracellular ions, metabolic pathways, and the control of gene expression. Knowledge of these basic mechanisms of cellular homeostasis is now being applied to the flow cytometric study of immune dysregulation. Various flow cytometric techniques for measuring apoptosis are summarized. PMID- 1605910 TI - The polymerase chain reaction for detection of T-cell antigen receptor expression. AB - Applications of the polymerase chain reaction have revolutionized the field of immunogenetics, particularly in studies of human leukocyte antigen class II polymorphism, and more recently in the analysis of T-cell receptor usage. However, the enormous diversity and variability of the T-cell receptor complex have made the amplification of the complete repertoire difficult. Several methods have been devised to address this problem. Each system is described with recent examples of its use and an assessment of its advantages and disadvantages. The use of quantitative polymerase chain reaction in T-cell receptor analysis is also discussed. The elucidation of the T-cell repertoire involved in a pathogenic process can have therapeutic implications, given the success of reversing experimental autoimmune disorders by directing specific forms of immunotherapy against V region gene products. PMID- 1605912 TI - Lymphocyte development. PMID- 1605911 TI - Recombinant globulins: novel research tools and possible pharmaceuticals. AB - A novel approach to the study of proteins is the construction of chimeras consisting of a target protein fused to an immunoglobulin constant domain. These recombinant globulins have been used in the identification of ligand-receptor pairs, determination of functional consequences of receptor engagement, the elucidation of structural domains necessary for ligand binding, and as potential therapeutic agents. PMID- 1605913 TI - Immunological techniques. PMID- 1605914 TI - Autoradiographic analysis of [3H]Ryanodine binding sites in rat brain: regional distribution and the effects of lesions on sites in the hippocampus. AB - Quantitative and qualitative autoradiographic methods together with lesion approaches were used to determine the distribution of [3H]ryanodine binding sites in rat brain and the neuronal localization of these sites in the hippocampus. In normal animals, levels of [3H]ryanodine binding sites ranged from a low of about 1 fmol/mg tissue in subcortical structures to a high of 12-18 fmol/mg tissue in subregions of the hippocampus and the olfactory bulb. Relatively high densities of sites (5-9 fmol/mg tissue) were also seen in the olfactory tubercle, most areas of the cerebral cortex, accumbens nucleus, striatum, lateral septal nuclei, pontine nucleus, superior colliculus and granule cell layer of the cerebellum. Specific binding was undetectable in white matter. In experimental animals, intracerebral injections of kainic acid caused neuronal degeneration and a near total depletion of [3H]ryanodine binding sites in the dentate gyrus and in fields CA1, CA2 and CA3 of the hippocampus. Injections of kainic acid that left dentate granule cells largely intact while destroying all neurons in field CA3 had no effect on binding sites in the dentate gyrus. However, these lesions substantially reduced the density of binding in field CA3, leaving a narrow band of sites outlining the position of the degenerated CA3 pyramidal cells. Mechanical knife-cut lesions that severed the granule cell mossy fiber input to field CA3 reduced the density of binding sites in the CA3 region. The results indicate that [3H]ryanodine binding sites in brain are heterogeneously distributed and suggest that a proportion of these sites in the hippocampus may be contained in mossy fiber terminals where a presumptive calcium channel/ryanodine receptor complex may be involved in the regulation of calcium mobilization and/or neurotransmitter release. PMID- 1605915 TI - The distribution of pituitary adenylate cyclase-activating polypeptide-like immunoreactivity is distinct from helodermin- and helospectin-like immunoreactivities in the rat brain. AB - Pituitary adenylate cyclase-activating polypeptide (PACAP) is an amidated 38 residue polypeptide isolated from the ovine hypothalamus. Helodermin, a 35-amino acid peptide, and helospectins, peptides of 38 and 37 amino acid residues, have been isolated from lizard venom. PACAP, helodermin and helospectins share structural features and have a similar profile of pharmacological effects: they stimulate adenylate cyclase. We studied the distribution and characteristics of PACAP-like immunoreactivity in the rat brain with immunochemical and immunohistochemical methods and compared its distribution with that of helodermin and helospectin-like immunoreactivities. With radioimmunoassay, the highest concentrations of PACAP-like immunoreactivity were found in the hypothalamus and cerebellum. PACAP-immunoreactive cell bodies were located immunohistochemically in the supraoptic nucleus, paraventricular and periventricular hypothalamic nuclei, and in the central grey. PACAP-immunoreactive fibres and terminals were detected in the medial part of the central nucleus of amygdala, in the median eminence and neurohypophysis, and in the central grey. No PACAP-immunoreactive structures were observed in areas such as the cerebral cortex, hippocampus, or cerebellum. The distribution of PACAP-like immunoreactivity differed considerably from the distribution of helodermin- and helospectin-like immunoreactivities. The results of this study suggest that PACAP is a neuropeptide with a role in the regulation of endocrine function in the hypothalamo-hypophyseal axis. PMID- 1605916 TI - Are there salvage routes within the general secretory pathway in yeast? AB - It is generally accepted that both extracellular protein secretion and plasma membrane expansion in yeast occur basically as in higher eukaryotic cells. In addition to the constitutive (default) secretory pathway, some specialized mammalian cells possess a regulated route which at present has not been detected in yeast. However, there is a body of experimental results suggesting that under certain circumstances export of integral plasma membrane and exocellular proteins may take place through alternative (salvage) pathways. The existence of these latter routes would enable the yeast cell to adapt more efficiently to distinct or adverse conditions requiring the secretion of discrete amounts of specific sets of proteins. PMID- 1605917 TI - Effect of aeration rate on the alcoholic fermentation of whey by Kluyveromyces fragilis. AB - In this paper, the influence of aeration rate on the alcoholic batch fermentation of whey by Kluyveromyces fragilis NRRL Y-2415 was investigated. Assays in 1.5-L fermentor using concentrated whey permeate containing 100 g/L of lactose were carried out at different oxygen supply rate (KLaC*) from 0 to 82 mmol/Lh. Optimum response was obtained at 14 mmol/Lh: ethanol production rate reached was 3.4 g/Lh yielding 0.46 g of product per gram of initial lactose. An increase of KLaC* from 0 to 14 mmol/Lh improved the ethanol production: maximum specific ethanol production rate (qpm) increased 3.3 times from 0.3 to 1.0 g/gh. For higher aeration levels, ethanol production diminished and biomass formation was stimulated. The declination of qpm and the increase of microns at higher aeration level lead to conclude the importance of a controlled oxygen supply in order to obtain the required balance between yeast biosynthetic needs and ethanol production. PMID- 1605918 TI - Methanosarcina mazei JC2, a new methanogenic strain isolated from lake sediments, that does not use H2/CO2. AB - A new mesophilic methanogenic strain, which produced methane from acetate, methanol, and methylamines, was isolated from lake sediments obtained from the lake Banyoles, near Girona (Spain). The cells were irregular in shape, from 1 to 3 micron in diameter, aggregated in masses of a few to several hundred units. Colonies were about 1-2 mm and irregularly shaped. Their color was yellow or white. Growth occurred throughout the pH range of 5 to 9 with optimal growth around pH 7. The optimal growth temperature was 37 degrees C. The molar deoxiribonucleic acid base composition was 37.2% (G + C). Studies of DNA homologies showed that this isolated was a strain of Methanosarcina mazei, but it differs from other reported strains, in that was not able to use H2/CO2 for growth or methane production. PMID- 1605919 TI - [Density and activity of microorganisms of the carbon cycle under the canopy of Myrica gale L]. AB - Plants, especially actinorhizal, regulate edaphic microflora through various ways, modifying thus nutrients recycling. Myrica gale effect on microorganisms in the carbon cycle is studied in this work by comparing soil samples collected under the canopy in summer and control samples. The results indicate that under M. gale C-organic and N-total concentration and anaerobic cellulolytic, hemicellulolytic and amilolytic density increase, and pH, C/N ratio and aerobic cellulolytic microorganisms density decrease. Microbial activity in soil is also modified. PMID- 1605920 TI - Single cell protein production from beet pulp by mixed culture. AB - Different mixed cultures of Trichoderma reesei and a yeast were cultivated on beet pulp (BP)-containing medium. T. reesei and Kluyveromyces marxianus offered a combination that gave high SCP yields (51%) and efficiently converted BP into proteins (39.4%). The yeast extract in the basal medium could be substituted and the BP level multiplicated from 2 to 4% upon using mixed culture of T. reesei and K. marxianus. Under these conditions the protein yields reached to a maximum value of 54% and highest efficiency of BP conversion into proteins (41.8%). The obtained protein proved to contain all essential amino acids, which compared favourably with those of the FAO guideline and soy bean oil meal. PMID- 1605921 TI - The occurrence of Salmonella serotypes in marine recreational waters of Valencia, Spain. AB - Salmonellae serotypes were studied in order to know their prevalence in marine recreational areas of Valencia. Two hundred eight strains were isolated. The strains belonging to serogroups B, C, D, E and G. The serotyping yielded twenty one different serotypes. The most frequent salmonellae serotypes were S. anatum and S. bredeney. Our results were compared with those reported by other authors in Spain. PMID- 1605922 TI - Studies on the distribution of the Paramecium aurelia species complex of Poland. AB - Species of the Paramecium aurelia complex occurred in the studied regions of the Carpathians and the Sudetes Mts with varying frequency. P. novaurelia appeared most often, P. biaurelia occurred less frequently but was also very characteristic, both species prevailed over P. primaurelia. P. tetraurelia and P. triaurelia were very rare. PMID- 1605923 TI - Structure and intramolecular hydrogen bonding of 1-phenazinecarboxylic acid. AB - C13H8N2O2, Mr = 224.22, monoclinic, P2(1)/n, a = 18.149 (2), b = 14.2768 (9), c = 3.8191 (3) A, beta = 92.029 (6) degrees, V = 988.95 A3, Z = 4, Dx = 1.51 g cm-3, lambda (Cu K alpha) = 1.54178 A, mu = 7.61 cm-1, F(000) = 464, T = 163 (1) K, R = 0.037 for 1479 data with I greater than or equal to 2 sigma (I). An intramolecular hydrogen bond is observed between the carboxyl hydrogen atom and the nearby nitrogen atom with the N...O distance being 2.67 A. PMID- 1605924 TI - Structure of tBuCO-Gly-Gly psi [CH2-N+H2]NHEt.BPh4-. AB - N-(tert-Butylcarbonylglycylaminoethyl)-N-(ethyl)ammonium tetraphenylborate, C11H24N3O+2.C24H20B-, Mr = 549.57, triclinic, P-1, a = 11.567 (2), b = 11.922 (2), c = 14.484 (3) A, alpha = 70.99 (2), beta = 74.83 (2), gamma = 59.33 (1) degrees, V = 1613.1 A3, Z = 2, D chi = 1.13 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 4.69 cm-1, mu Rmax much less than 1, F(000) = 592, T = 293 K, R = 0.058 for 3491 observed reflections. This pseudopeptide is folded by a short N(+)-H ... O = C hydrogen bond (N3 ... O1 = 2.81 A) which closes a ten-membered ring. This results in a beta-turn structure that can be classified as type II on the basis of the conformational angles for the N-terminal glycine. The conformational angles phi 1, psi 1, phi 2 and psi 2 are -53.4 (6), 139.7 (4), 91.5 (5) and -62.6 (6) degrees respectively. PMID- 1605925 TI - Structure of tBuCO-Val psi [NH-CO]NHtBu. AB - N-Isobutylidenedipivalamide, C14H28N2O2, Mr = 256.39, orthorhombic, P2(1)2(1)2(1), a = 16.656 (2), b = 9.751 (2), c = 10.583 (2) A, V = 1718.8 A3, Z = 4, D chi = 0.99 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 4.56 cm-1, mu Rmax much less than 1, F(000) = 568, T = 293 K, R = 0.081 for 887 observed reflections. The geometrical parameters of this retro-peptide molecule are quite similar to the standard values for peptides. Conformational angles are phi = -101 (1), phi' = 99 (1) degrees. PMID- 1605926 TI - Structure of MeCO-Gly psi [NH-CO]NHMe. AB - N,N'-Methylenediacetamide, C5H10N2O2, Mr = 130.15, orthorhombic, Pna2(1), a = 17.218 (1), b = 4.489 (1), c = 18.124 (1) A, V = 1400.8 A3, Z = 8, D chi = 1.23 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu Rmax much less than 1, mu = 7.19 cm-1, F(000) = 560, T = 293 K, R = 0.044 for 1318 observed reflections. This retro peptide molecule assumes two nearly identical conformational states (A phi = 93.2, phi' = 77.0; B phi = 90.6, phi' = 79.6 degrees) with planar trans amide functions. The bond lengths and bond angles are very close to the standard dimensions of the peptide group. PMID- 1605927 TI - Structure of MeCO-psi[NH-CO]Val-NHMe. AB - N,N'-Dimethylisopropylmalonamide, C8H16N2O2, Mr = 172.23, orthorhombic, Pbcm, a = 4.859 (1), b = 13.523 (2), c = 15,469 (2) A, V = 1016.4 A3, Z = 4, Dx = 1.12 g cm 3, lambda(Cu K alpha) = 1.5418 A, microRmax much less than 1, mu = 5.88 cm-1, F(000) = 376, T = 293 K, R = 0.060 for 665 observed reflections. Dimensions of this retropeptide molecule are quite similar to the standard values for peptides. The C alpha and C beta atoms are in a mirror (z = 1/4), so conformational angles are psi' = -psi = -110.4 degrees (2). PMID- 1605928 TI - Structure of disodium methyl phosphate hexahydrate. AB - 2Na+.CH3O4P2-.6H2O, Mr = 264.09, monoclinic, Pc, a = 7.277 (1), b = 6.298 (2), c = 11.477 (4) A, beta = 92.44 degrees, V = 525.5 A3, Z = 2, Dx = 1.669 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 35.26 cm-1, F(000) = 276, T = 298 K, R = 0.028 for 781 independent reflections. Three P-O bond lengths are the same (1.513 A) within experimental error, with the ester P-O bond length significantly longer [1.626 (3) A]. The Na ions are octahedrally coordinated by water O atoms and have no direct interaction with the phosphate O atoms. Water molecules form three hydrogen bonds with each phosphate O atom, except the ester O atom which at most forms one weak interaction. PMID- 1605929 TI - Structure of an anticonvulsant N-methyl-m-bromophenylsuccinimide. AB - 3-(3-Bromophenyl)-1-methyl-2,5-pyrrolidinedione, C11H10BrNO2, Mr = 268.11, triclinic P1, a = 11.606 (2), b = 11.832 (2), c = 10.370 (2) A, alpha = 101.84 (1), beta = 107.76 (1), gamma = 118.28 (2) degrees, V = 1085.7 (5) A3, Z = 4, Dx = 1.640 Mg m-3, lambda(Cu K alpha) = 1.54178 A, mu = 5.04 mm-1, F(000) = 536, room temperature, final R = 0.061 for 2971 observed reflections with I greater than 3 sigma(I) (of 3743 unique data). The only slight differences in conformation of the two independent molecules are in the inclination of the phenyl and five-membered rings. The torsion angle C4-C1-C11-C12 is -115.4 (4) degrees in molecule I and -131.6 (4) degrees in molecule II. The five-membered imide ring has the open-envelope conformation in molecule I [the deviation of C11 from the plane N11-C41-C21-C31 is -0.117 (3) A] and the twist conformation in molecule II [the deviations of C12 and C22 from the plane N12-C42-C32 are 0.117 (1) and -0.064 (1) respectively]. PMID- 1605930 TI - Structure of N-tert-butoxycarbonyl-L-phenylalanine benzyl ester. AB - C21H25NO4, Mr = 355.4, monoclinic, P2(1), a = 5.206 (2), b = 17.294 (4), c = 10.972 (2) A, beta = 98.91 (1) degrees, V = 976 (1) A3, Z = 2, Dx = 1.21 Mg m-3, lambda(Cu K alpha) = 1.5418 A, mu = 0.68 mm-1, F(000) = 380, T = 293 K, final R = 0.071 for 1186 observed reflections. The structure is stabilized in the a direction by means of intermolecular hydrogen bonds [N(1) ... O(2i) = 3.01 (1) A, (i) = x + 1, y, z]. The urethane amide bond adopts the trans conformation [H(1) N(1)-C(5) = O(2) = 169 (3) degrees]. The butoxycarbonyl (Boc) moiety is directed away from both the phenylalanine aromatic ring and the benzyl ester ring, in contrast to the arrangement observed in Bocphenylalanine phenacyl ester [Vlassi, Germain, Matsoukas, Psachoulia, Voliotis & Leban (1987). Acta Cryst. C43, 2173 2175]. The orientation assumed by the Boc group may be the result of steric restrictions imposed by both rings. PMID- 1605931 TI - Structure of (+)-(S)-1,3-dimethyl-6-oxiranyl-2,4-pyrimidinedione showing anti ASFV activity. AB - C8H10N2O3, Mr = 182.18, monoclinic, P2(1), a = 6.6405 (7), b = 7.9493 (9), c = 8.3662 (9) A, beta = 103.07 (1) degrees, V = 430.18 (8) A3, Z = 2, Dx = 1.41 Mg m 3, lambda (Cu K alpha) = 1.54184 A, mu = 0.879 mm-1, F(000) = 192, T = 298 K, R = 0.037 for 1247 reflections with Fo greater than or equal to 4 sigma (Fo). The configuration at C7 is S. The pyrimidine-2,4-dione ring is nearly planar [r.m.s. deviation: 0.010 (8) A] and is antiperiplanar with respect to the epoxide ring. This arrangement is stabilized by intermolecular C-H ... O interactions. PMID- 1605932 TI - Unusual diffraction of type B influenza virus neuraminidase crystals. AB - An unusual X-ray diffraction pattern by tetragonal crystals of a type B influenza virus neuraminidase was observed in that the odd-l reflections were missing or diffuse while the even-l reflections were sharp and strong. A statistical analysis showed that an error (epsilon) in the spacing of successive planes of neuraminidase molecules was randomly distributed along the c direction, which resulted in such an unusual diffraction pattern. The error epsilon follows the Bernoullian distribution and may be caused by a flexible loop on the top surface of the neuraminidase. PMID- 1605934 TI - Some applications of the phased translation function in macromolecular structure determination. AB - Although the phased translation function was first described some time ago [Colman, Fehlhammer & Bartels (1976). In Crystallographic Computing Techniques, edited by F.R. Ahmed, K Huml & B. Sedlacek, pp. 248-258. Copenhagen: Munksgaard], it has been little used, especially in the application of molecular replacement to macromolecular structures. Nevertheless, the procedure is relatively easy to apply and deserves wider use. In this paper the versatility of the phased translation function in a number of different applications is examined and experience gained in obtaining optimal results in protein structure determination by this method is reported. Examples given show how it can be used to position an oriented fragment, to locate independent components with respect to a common crystallographic origin and to choose correctly between enantiomorphic space groups. Its performance is compared with other translation functions in common use. PMID- 1605933 TI - Ab initio phase determination for spherical viruses: parameter determination for spherical-shell models. AB - The structure determination of canine parvovirus depended on the extension of phases calculated initially from a spherical-shell model [Tsao, Chapman, Wu, Agbandje, Keller & Rossmann (1992). Acta Cryst. B48, 75-88]. Such ab initio phasing holds the promise of obviating initial experimental phasing by isomorphous or molecular replacement, thereby expediting the structure determinations of spherical virus capsids. In this paper, it is shown how parameters such as radii, DNA density and particle positions may be determined and refined from diffraction data with sufficient precision to start phase extension from 20 A resolution for a virus of approximately 122 A radius. PMID- 1605935 TI - [Parallels in blood alcohol and breath alcohol border values and sequelae of "double track" forensic assessment]. AB - This paper deals with the regulation of fixing two limiting values, i.e. an BrAC dangerous limiting value ("AAK-Gefahrengrenzwert") and an absolute BrAC-value ("absoluter AAK-Grenzwert") according to the BAC-limiting values for the purposes of the forensic appraisement. It is referred to the uneven treatment of alcoholized road-users and to the partly unsolvable difficulties for the calculation with the WIDMARK-values. PMID- 1605936 TI - [Change in congener analysis caused by percutaneous absorption of propanol containing antiseptics]. AB - According to the forensic literature, an alteration of blood alcohol concentration through alcohol disinfection before venepuncture is unlikely, however, percutaneous resorption of alcohol containing antiseptics is well documented. There are no investigations available, elucidating to what extent this is also correct for congener alcohols, particularly propanol-1/-2, which have serum levels in range of mg/l. In experiments with surgical hand and local skin disinfection, carried out with and without oral alcohol, relevant levels of propanol-1/-2 between 0.2 and 2 mg/l were measured. We conclude, that the routine clinical use of antiseptics is able to alterate and to falsify congener levels and can lead to incorrect interpretation of congener analysis. PMID- 1605937 TI - [Prevalence of alcohol in fatalities in forensic medicine]. AB - Blood alcohol tests were carried out at the Institute of Forensic Medicine of the University of Hamburg in 1,000 sudden unexpected natural deaths and non-natural deaths (590 males, 410 females) during the first six months of 1989. In 18.6% of the cases (142 males, 44 females) a blood alcohol concentration of more than 0.1% was found. The blood alcohol concentration ranged from 0.1 to 1% in 87 cases; in 99 cases the blood alcohol concentration exceeded 1%; there were 17 fatalities with more than 3%. More than 95% of blood alcohol concentration values exceeding 2.5% were found in the age group of 40-69 years. As expected positive blood alcohol estimations and especially high blood alcohol concentrations were found in non-natural deaths. However, many cases with relevant blood alcohol findings had been classified as "sudden natural death" and were not investigated by autopsy. In 74 cases alcohol blood tests were ordered by the police. PMID- 1605938 TI - [Detection of extraneous gases in breath alcohol analysis]. AB - The influence of interfering substances on breath-alcohol measurements is handled by the OIML by giving a list of test gases and prescribing the maximum permissible cross-sensitivity of a measuring system. The expertise of the Federal Health Office for evidential breath analysers prefers an other way to detect interfering substances in expired air. By the use of two measuring systems with different analytical specificity interfering substances as e.g. methanol, isopropanol, aceton, ethylacetat, and toluene cause measured values with a difference which exceeds the limits permitted in the OIML recommendations. The same happens with interfering substances in expired air which are most commonly used by sniffers as e.g. Pattex, Uhu adhesive, or petrol. PMID- 1605939 TI - [Precision control in blood alcohol determination]. AB - The German supreme court (BGH [1]) summons that by proclaiming four or five single measuring values of every blood alcohol determination to prove that the resulting standard deviation lies under the highest amount stated in the official verdict of 1989 (10). On the one hand the control of the proceedings must be guaranteed by the successful participation of the ring tests, yet on the other hand the evidence to retroactively prove the accuracy of every blood alcohol determination from it's single values is always called for anew. In the example case the average value is 1.11 g/1000, the standard deviation is 0.036 g/1000. The standard deviation summoned by the BGH (1) is thereby exceeded. On account of the fundamental scientific regularies the parameter standard deviation is not qualified to retroactively verify the required accuracy of the procedure by means of the single values. The blood alcohol result in question can be used without proviso. A reduction of the present approved 10% variation of the single values is not significant. Only according to todays accuracy requirements does this limit nearly appear to be appropriate. PMID- 1605940 TI - [Applying the revoked driving privilege law according to section 25 StVG]. AB - The driving ban is an urgent mean of education. If a fine is fixed against a motorist on account of drunk driving, a driving ban has usually to be ordered according to section 25 section 1 sentence 2 StVG, because the driving of a motor vehicle in a stage of drunkness represents a dangerous way of behavior. There are nevertheless other comparatively dangerous ways of behavior on the roads; to that belongs especially the infringe of the permissable speed limit. For that reason there are more legal driving bans necessary. PMID- 1605941 TI - Dementia and the life-prolonging technologies used: an ethical question. PMID- 1605942 TI - Clinically diagnosed Alzheimer disease: neuropathologic findings in 650 cases. AB - Despite the introduction of formal clinical criteria for Alzheimer disease (AD), the clinical diagnosis of AD remains one of exclusion of other dementias. To determine the accuracy of a clinical diagnosis of AD as made by practicing physicians, we reviewed the clinicopathologic records of a dementia brain bank and summarized the literature. Of 650 demented patients diagnosed during life as having AD, at autopsy 505 (78%) had AD with or without other neuropathologic conditions; only 390 (60%) of these had AD as the only neuropathologic condition. Of the remaining 145 (22%) patients with no neuropathologic evidence of AD, 39 had the nigrostriatal changes of Parkinson disease (PD), 25 had nonspecific degenerations, 15 had Pick disease, 14 had multiple infarcts, and 11 lacked any neuropathologic abnormality. Although the overall clinical accuracy for AD was lower than that summarized from the literature, clinical accuracy improved significantly between 1986 and 1990. In our broad sample of practitioners, accuracy of clinical diagnosis of AD may be improving, but continues to be hampered by difficulty in distinguishing the dementia of AD from certain dementing conditions and from AD mixed with other neuropathologic conditions. PMID- 1605943 TI - Growth hormone responses to cholinergically active drugs in patients with dementia of the Alzheimer type. AB - Patients with dementia of the Alzheimer type (DAT) reportedly have reduced concentrations and function of some brain messengers, particularly acetylcholine and somatostatin, not only in the cerebral cortex, but also in subcortical structures, e.g., the hippocampus and the hypothalamus. We wished to determine the responsive pattern of DAT patients to neurohormonal and pharmacologic probes affecting growth hormone (GH) release through an interaction with hypothalamic cholinergic and somatostatinergic (SS) neurons. In 10 DAT patients, pyridostigmine (120 mg orally, p.o.), an inhibitor of acetylcholinesterase, induced an increase in GH levels similar to that elicited by the drug in age matched controls. In 9 DAT patients, administration of GH-releasing hormone (GHRH, 1 microgram/kg body weight, intravenously, i.v.) induced an increase in plasma GH not different from that evidenced in control subjects. In DAT patients the GHRH-induced GH increase was completely inhibited by pretreatment with atropine (1 mg intramuscularly, i.m., 15 min before administration of GHRH). These findings are considered to indicate that in DAT patients, hypothalamic cholinergic and somatostatinergic neurons involved in control of somatotropic function are preserved. PMID- 1605944 TI - Alzheimer disease (AD): aspirin prophylaxis and therapy. PMID- 1605945 TI - Anticoagulant therapy in treatment of dementia. PMID- 1605946 TI - The seminal role of beta-amyloid in the pathogenesis of Alzheimer disease. AB - New molecular information about Alzheimer disease (AD) is appearing at an unprecedented rate. Much interest centers on the beta A4 amyloid protein, which is progressively deposited in senile plaques and blood vessels in AD brain tissue. The discovery that some kindreds with familial AD have a mutation in the gene coding for the beta A4 amyloid precursor protein (APP) suggests that this mutation alone may be sufficient to cause the full spectrum of clinical and pathological changes that characterize AD. Although APP point mutations may turn out to be relatively rare causes of AD, the idea that accelerated beta A4 deposition is an early and critical event in many patients continues to gain support from studies in humans, animals, and cultured cells. Identification of the biochemical steps leading to production of the beta A4 peptide from APP is now a critical issue. Recent reports indicate that normal lysosomal processing pathways can produce carboxyl-terminal fragments of APP that contain the entire beta A4 sequence, and are therefore potentially amyloidogenic. The mechanisms by which such intermediate forms are further processed and released, resulting in extracellular beta A4 deposits in plaques and vessels, are yet to be determined. It is likely that full elucidation of the beta A4-producing pathways will ultimately yield new therapeutic approaches to this complex and tragic disorder. PMID- 1605947 TI - Processing asymmetries for complex sounds: comparisons between behavioral ear advantages and electrophysiological asymmetries based on quantitative electroencephalography. AB - This experiment extends our earlier work on individual differences in ear advantages for complex sounds (Lauter 1982, 1983, 1984) to examine the results of combined behavioral and qEEG testing in the same subjects. Results include: (1) between-subject differences in absolute values together with between-subject agreements in terms of relative values, observed both for ear advantages (EAs) and hemisphere advantages (HAs); (2) within-subject agreement between behavioral (EAs) and physiological (HAs) measures of asymmetries; and (3) preliminary findings related to the interpretation of qEEG asymmetry data, such as the influence of hand movements on auditory-cortex qEEG recordings, and persistence of activation effects in which asymmetries evoked during a stimulation condition may be reflected in resting asymmetries observed during a subsequent control condition. PMID- 1605948 TI - Neural and behavioral correlates of visual recognition memory in 4- and 8-month old infants. AB - The neural and behavioral correlates of the 4- and 8-month-old infant's ability to distinguish between frequently and infrequently presented familiar and novel events was examined. Cortical event-related potentials (ERPs) were recorded as infants were familiarized to two faces. During the test trials that followed, one of these faces was presented frequently, and the other infrequently; on each of the remaining 20% of the trials, a previously unseen, novel face was presented. Following the ERP phase, infants' looking times were recorded to pairs of faces, some of which had been seen during the ERP testing, and some of which had not. At 4 months the ERP activity invoked by the three classes of events was similar, suggesting that infants were unable to distinguish among them. At 8 months the ERP activity differed only between the Infrequent Novel events and the two classes of familiar events, but did not differ between the frequently and infrequently presented familiar events. The ERP findings complement previously reported data from 6-month-old infants in describing a trend whereby infants become increasingly able to respond to stimuli on the basis of whether they have been seen before, and not on the basis of how often they had been seen. The behavioral data at both 4 and 8 months were less clear cut than the ERP data. These findings are discussed in the context of the neural and cognitive processes involved in dissociating probability information from novelty detection. PMID- 1605949 TI - Variations in characteristic perceptual asymmetry: modality specific and modality general components. AB - The current study investigates sources of between-subjects variation in asymmetry scores on visual half-field and dichotic listening tasks. For each of these presentation modalities, subjects were given multiple laterality tasks. Results indicate that about 50% of the between-subjects variations in asymmetry scores in each modality is attributable to individual differences in perceptual asymmetries that are not stimulus-specific, referred to as "characteristic perceptual asymmetries" in this paper. In addition, the question of whether individual differences in characteristic perceptual asymmetries are modality specific, modality general, or both was investigated by entering subjects' asymmetry scores from visual half-field and dichotic listening tasks into a principal component analysis. The results of this analysis indicate that there are both modality specific and modality general influences on subjects' characteristic perceptual asymmetries. PMID- 1605950 TI - An empirical test of two opposing theoretical models of prefrontal function. AB - The purpose of this study was to compare the validity of two models which contrast with each other in the manner in which they integrate neuropsychological tests into distinct prefrontal constructs. The first prefrontal model consists of five distinct functional constructs drawn from human clinical neuropsychology. The second model, elaborated by Goldman-Rakic, is based primarily on monkey research and postulates a basic prefrontal function, "on-line representational memory," which guides behavior in the absence of, or despite discriminative environmental stimuli. In the latter model, distinct prefrontal functional constructs are primarily defined in terms of various types of representational memory involved in specific tasks. Eleven "prefrontal" measures were obtained from 259 normal adults, stratified for age, education, and sex. Confirmatory factor analyses revealed that the Goldman-Rakic model "fit" the data better than the model derived from human clinical neuropsychology, while several constructs commonly used in human neuropsychology were refuted. It was concluded that new research on brain-damaged humans with a view to understanding prefrontal function might benefit from using the Goldman-Rakic model as a starting point. PMID- 1605951 TI - Inhibition and the control of behavior. From Gall to Freud via Phineas Gage and the frontal lobes. AB - In his On the Functions of the Brain and Each of Its Parts, Franz Joseph Gall proposed that significant behaviors resulted from certain independent, irreducible, and fundamental faculties or propensities. There seems to be nothing in his system for explaining how two or more faculties interact, especially how one comes to predominate over another, other than the implicit notion that the stronger will be manifested. This peculiarity of Gall's system is consistent with the predominately "excitatory" physiology of his time in which there was no place for an independent inhibitory process. Despite the experimental demonstration of inhibitory phenonema, the sensory-motor physiological theories in the last three quarters of the 19th century were similarly deficient. The lack is seen most clearly in the experimental and clinical literature on frontal lobe function, especially in relation to the kinds of changes seen in the Gage case. The deficiencies of sensory-motor physiology are also to be found in Freud's model of the mental apparatus and in his concept of inhibition via a lateral cathexis. In the paper an attempt is made to trace the historical sequence of these ideas and to make their experimental and theorectical basis explicit. PMID- 1605952 TI - Common artifacts encountered in thoracic magnetic resonance imaging: recognition, derivation, and solutions. AB - The article discusses the many types of thoracic magnetic resonance imaging artifacts, their derivations, and their current solutions. Magnetic resonance imaging artifacts of the thorax can be divided into two major categories. First, there are machine-related artifacts related to the machine's hardware: the intrinsic magnetic field, chemical shift, magnetic susceptibility, radio frequency leaks, metal artifacts, B1-homogeneity, gradient coils, truncation, aliasing, zipper artifacts, artifacts related to the surface coil profiles, pulse profiles, and crosstalk. Second, there are artifacts related to motion: voluntary patient motion, involuntary motion, and physiologic motions. Each one of these artifacts, and their solutions, will be discussed. PMID- 1605953 TI - Abdominal magnetic resonance imaging: optimization and artifact suppression. AB - Optimized spin-echo images must contain adequate tissue contrast, which can be realized by selecting proper repetition time, echo time, and flip angle. Although conventional T2-weighted images have long acquisition time and limited signal-to noise ratio (SNR), multiecho conjugate techniques address both of these problems, SNR, resolution, and anatomic coverage are interrelated issues that must be addressed together. Motion artifact reduction techniques include averaging, physiologic monitoring, gradient-moment nulling, spatial presaturation, and fat suppression. Best results are obtained by combining multiple methods when possible. PMID- 1605954 TI - Image artifacts in fast magnetic resonance imaging. AB - Image artifacts are unwanted, spurious signal intensities that interfere with clinical diagnosis. This article gives an overview of image artifacts in magnetic resonance imaging. We discuss the causes of these artifacts, provide clinical examples, and offer solutions to avoid them. PMID- 1605955 TI - Chemical shift magnetic resonance imaging: applications in the abdomen and pelvis. AB - Chemical shift imaging allows unambiguous separation of lipid and water signals. Useful images include opposed-phase (water minus fat) and fat-suppressed images, which can be obtained with spin-echo or gradient-echo methods. Chemical shift techniques can be used to reduce artifacts, to expand dynamic range, to diagnose fatty infiltration of the liver, to distinguish between benign and malignant adrenal lesions, and to diagnose benign teratomas in women. PMID- 1605956 TI - [The septal button: an alternative to the reparative surgery of septal perforations]. AB - There are many surgical approaches for closure of nasal septum, most of which present technical difficulties. Moreover, the clinical results are, as yet, unsatisfactory. Prefabricated prostheses have been effective for treatment of smaller perforations, and are an excellent alternative in a great number of cases. We present an optional surgical technique to deal with this increasingly common problem. PMID- 1605957 TI - [Primary malignant melanomas of the nasal fossae]. AB - Melanoma of the nasal and paranasal sinus mucosa represented less than 1% of all melanomas. Melanoma to be localized commonly in nasal septum and your prognosis is poor. We presented three cases with a mean age of 75 years. The tumor was localized in nose. The melanocytes were presented in only case. All the tumoral cells stained with S-100 and HMB-45. In a case the vascular invasion was presented. Only a patient was treated with surgical excision. Two patients death 8 months after diagnosis. PMID- 1605958 TI - [Surgery of the thyroid. A review of 150 cases]. AB - We present a review of 150 partial or total thyroidectomies, only 126 of which were considered valid for this study. They were performed during the period from March 1985 to March 1990 to treat benign or malignant thyroid pathologies judged to be susceptible to surgery. Only three permanent complications resulted: a definitive hypothyroidism and two recurrent paralyses, both in cases of papillary carcinomas, one with extracapsular invasion which required the sacrifice of the nerve. PMID- 1605959 TI - [The incorporation of acyclovir into the treatment of peripheral paralysis. A study of 45 cases]. AB - The relation between use of acyclovir and facial nerve palsy prognosis was studied. In a randomised study, steroids or steroids + acyclovir (oral doses for Bell's palsy, and intravenous doses for Ramsay Hunt's syndrome) were given to 45 patients with facial palsy. There was a significant reduction of sequelae in patients treated with acyclovir in the group of Ramsay Hunt's syndrome (n = 15) (p less than 0.05). There were no significant differences in the group of Bell's palsy (n = 30) (p greater than 0.05), treated with acyclovir compared with steroids. PMID- 1605960 TI - [Our results in the surgery of otosclerosis]. AB - A statistical study is made of the results of 78 stapedectomies carried out during the last six years in the Virgen de la Salud Hospital of Toledo, Spain. An auditive gain of 90%, averaging 27 dBs, was found. Other parameters assessed were age, sex, prosthesis type, and failures. PMID- 1605961 TI - [The identification of wave I in ABR, ear-canal electrode and electrocochleography]. AB - The diagnosis value of auditory brainstem response (ABR) lies in the fact that they make possible to measure the times conduction of the pathway from the cochlea to the topo part of the brainstem, enabling the diagnosis in an objective way of hearing deficits and their classifying as well. The analysis of the times of conduction are based on the measuring of the latency of waves and the interwave intervals, being fundamental the latency of waves I and V and the interval between them (I-V). But sometimes the registrations of ABR, obtained at intensities nearing hearing threshold or in many patients with significant hearing loss obtained through the traditional method from the scalp, do not permit as the identification of wave I, which causes a reduction in the value of ABR diagnosis. Our work tries to analyze the different techniques which could solve that reduction. To achieve it we have to compare the registrations of ABR obtained from the scalp to those obtained using a EAR canal electrode and to Auditory Nerve Action Potential obtained through Transtympanic Electrocochleography, analyzing the latency, the amplitudes and the intervals of the different waves and specially the growth in the amplitude of wave I, and the subsequent improvement given back to ABR all their diagnosis value.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1605962 TI - [Neurinoma of the 8th nerve]. AB - Before an acoustic neuroma case, with a buds evolution, coincident with influenza, actually the most significant explorations are revised, a protocol is proposed, and discussing the convenience to repeat specific explorations after a year when the first explorations have been iniciativelly negatives; being insinuated the possibility that some virus infections could act as a stimulus in the speed of neuromas growth. PMID- 1605963 TI - [Schwannoma of the spinal nerve]. AB - A years old woman with a spinal nerve schwannoma is reported. Treatment and main clinical and histopathologic features of this very unusual location are discussed. PMID- 1605964 TI - [An epidemiological analysis of the trends in laryngeal cancer mortality and morbidity in Spain and the Commune of Valencia (1977-1985)]. AB - An epidemiological study is made of the evolution of cancer of the larynx in the Valencia Community (Spain) in comparison with the nationwide situation, during the period 1977-1985. Both morbidity and mortality are evaluated based on the data published by the National Institute of Statistics (Instituto Nacional de Estadistica INE). Indirect data standardization was decided on, given the lack of information by age groups. The results reveal an increase in the incidence during the study period in all provinces--both morbidity and mortality standing out in the province of Castellon; in Alicante the figures were lower in comparison with the national values. PMID- 1605965 TI - [The use of computerized axial tomography in the assessment of laryngeal neoplasms. A comparison between the clinical findings and anatomicopathological study]. AB - Twenty cases of laryngeal neoplasms are presented. We analyse tumor extent, invasion of the laryngeal cartilages and cervical metastasis and findings histopathologic with computed tomography in preoperative evaluation and surgical strategy. PMID- 1605966 TI - [A morpho-photometric study of laryngeal epidermoid carcinoma]. AB - At the moment the use of quantitative techniques in anatomopathology is more and more frequent. In this study the authors use for the first time the morpho photometry approach in epidermoid carcinomas of the larynx coming from filed material. In this way they are checking if this method adds anything to conventional anatomopathology. PMID- 1605967 TI - Management of the nephrotic child. PMID- 1605968 TI - Evolution of bereavement counselling in sudden infant death syndrome, neonatal death and stillbirth. AB - There have been changing attitudes to death and grief in Western society in recent centuries. During the twentieth century complex medical and social changes have resulted in changing attitudes to and experiences with death. Specifically, the impact of death in childhood is reviewed. In recent decades sudden and unexpected death associated with stillbirth, the newborn and infants appears to have a more profound affect on the bereaved parents than in the past when the overall death rates in childhood were higher. The evolution of parent support groups developed since the 1960s to alleviate the psychological trauma of unexpected and sudden death in childhood has been traced. These groups were founded initially for support with sudden infant death syndrome and later extended to include families with stillbirth and neonatal death. PMID- 1605969 TI - Surfactant replacement therapy. PMID- 1605970 TI - Which antibiotic for epiglottitis? PMID- 1605971 TI - Single daily dose ceftriaxone therapy in epiglottitis. AB - Ceftriaxone as a single daily intravenous dose for 5 days was used to treat seven patients with proven Haemophilus influenzae epiglottitis. All children responded favourably. The serum levels achieved exceeded the MIC by up to 1500 times at the trough level during and for up to 24 h after the completion of the treatment. Side effects were mild and transient and did not disrupt the continuity of the treatment. Ceftriaxone potentially offers a number of clinical and economic advantages in the management of epiglottitis. PMID- 1605972 TI - The management of acute laryngo-tracheo-bronchitis (croup): a consensus view. AB - The management of croup relies upon the traditional clinical skills of observation and examination. Parental involvement is essential and the appropriate reassurance of the patient is important. Endotracheal intubation is required only in a small percentage of children whose airway is compromised to such a degree as to produce fatigue and/or near occlusion. PMID- 1605973 TI - Motorcycling attitudes and behaviours. I. 12 and 13 year old adolescents. AB - The death and serious injury of adolescent motorcyclists is a major public health problem. Effective preventive strategies depend on knowledge about target populations. The attitudes and patterns of exposure to motorcycling of 730 13 year old New Zealand adolescents are described. Fifty-two per cent could ride a motorcycle, a further 13% intended to learn, 22% had driven on-road, and 60% had ridden as pillion passengers on-road. Significantly more males than females were riders (P less than 0.001) and had ridden as pillion passengers (P less than 0.05). More male than female non-riders intended to learn (P less than 0.001). Eighty per cent of the sample recognized road 'accidents' as the main cause of death for their peers, and 31% had known a motorcyclist killed or injured. Seventeen per cent of on-road riders had not worn a helmet when last riding. Few statistically significant differences in risk perception were obtained between males and females or riders and non-riders. Preventive options are discussed. PMID- 1605974 TI - Cycling health beliefs, crash experiences and night cycling behaviour of 13 year olds. AB - The relationship of selected health beliefs to self-reported crash experiences, cycling at night and the use of tail-lights at night was examined for a sample of 730 13 years olds. The questions relating to cycling health beliefs were similar to those asked by Weinstein in his study of unrealistic optimism about susceptibility to a range of health problems. They included: vulnerability, worry, controllability, chance, barriers, seriousness, apprehension and safety. The majority of 13 year olds interviewed did not exhibit a strong optimistic bias regarding their vulnerability and skills as safe cyclists. In general the majority considered a crash involving a car would most likely be serious and only a minority said they were not worried about being involved in such a crash. In addition, the majority did not consider that crashes are a matter of chance or that there are significant barriers to adopting safety measures. They tended to consider the chances of being apprehended by a traffic officer for failure to use a tail-light at night as being low. Overall the univariate analyses failed to show a consistent pattern of relationships between health beliefs and the two cycling behaviours. The same was true for crash experiences. The joint effects of beliefs and crash experience on the use of a light at night were examined using logistic regression. The results suggest that the health beliefs work in an additive way as far as boys are concerned, but that they have very little influence on the behaviour of girls. The model for boys suggests that the variables have a relatively small influence on behaviour. PMID- 1605975 TI - Organ weight/bodyweight ratios: growth rates of fetal organs in the latter half of pregnancy with a simple method for calculating mean organ weights. AB - Ratios for major organ weights compared with bodyweights of 1023 stillborn and liveborn babies who lived less than 72 h are presented. The ratios were calculated for 2 week increments of gestational age from 20 to 43 weeks and clearly depict the relative growth of fetal organs during the last half of pregnancy. The ratios for heart and for kidneys were virtually constant for the whole period of gestation examined. The ratios for thymus and spleen increased between 20 and 30 weeks gestation and then became constant, although the ratio for the spleen dropped slightly during the last 6 weeks. The ratios for liver, lungs and adrenals decreased between 20 and 30 weeks gestation, and then steadied. The ratio for brain declined very slowly throughout the period examined. An observation of practical importance was that all organ weight/bodyweight ratios were virtually constant after 30 weeks gestation. Approximate mean organ weight/bodyweight ratios between 30 and 43 weeks gestation were: heart 0.007, lungs 0.02, spleen 0.003, liver 0.04, kidneys 0.01, adrenals 0.003, thymus 0.004 and brain 0.13. By multiplying the mean ratio by the total bodyweight, the approximate mean weight for a particular fetal organ can be calculated in situations where charts of normal organ weights are not at hand. PMID- 1605976 TI - Biphasic rise of serum immunoglobulins G and A and sex influence on serum immunoglobulin M in normal Chinese children. AB - A study was conducted on 751 healthy children from child health clinics, kindergartens and schools, and 80 normal adults to establish reference ranges for serum immunoglobulins (Ig) G, A and M concentrations in normal Chinese. Serum IgG, IgA and IgM concentrations were determined by nephelometry. Serum IgG and IgA were shown to have a significant rise during the preschool age as well as at puberty with a plateau phase in between. This biphasic maturation profile has not been reported in Caucasians and the reasons for the observed difference have yet to be elucidated. Serum IgM concentrations were shown to be higher in females than in males, reaching significance in most age groups beyond 4 years of age. The difference between the two sexes in Chinese was of similar magnitude as that reported for Blacks and Caucasians, that is, 30%. Our findings support the hypothesis that the human X chromosome may carry quantitative genes for IgM. PMID- 1605977 TI - High cervical cord injury: medical, nursing and psychosocial aspects of rehabilitation. AB - Two patients with traumatic high cervical cord injury are described. Both patients required long-term ventilatory support. Diaphragmatic pacing has been successful in meeting their ventilatory requirements and improving their quality of life. Both patients are now living in their own homes. Their medical, nursing and psychosocial needs have been met by multi-disciplinary team involvement and their ongoing support in the community. PMID- 1605978 TI - A review of therapeutic monitoring of chloramphenicol in patients with Haemophilus influenzae meningitis. AB - Two hundred and seventy-seven serum chloramphenicol concentrations in 90 patients with Haemophilus influenzae type b meningitis were analysed retrospectively. Most patients were given chloramphenicol 25 mg/kg 6 hourly initially. Chloramphenicol concentrations were categorized as pre-dose ('trough') or post-dose ('peak'). Twenty-six per cent of the results were in the potentially toxic range (above 30 mg/L), and 18% were below 10 mg/L. Analysis of 46 pre- and post-dose measurements showed that for the intravenous (i.v.) route of administration, 23% of the pre dose concentrations were higher than the corresponding post-dose levels and, for the oral route, 42% of the pre-dose levels were higher. Multivariate analysis of covariance demonstrated that chloramphenicol concentrations decreased significantly with increasing number of days of treatment and that the decline was steeper with i.v. administration. The results of this study emphasize the need for therapeutic monitoring of chloramphenicol concentrations, and suggest that chloramphenicol should be given as a loading dose of 40 mg/kg, followed by 25 mg/kg per dose 8 hourly for 3-4 days and then 6 hourly. PMID- 1605979 TI - Familial cyanotic breath-holding spells. AB - Breath-holding spells can be a source of considerable parental anxiety and are a frequent cause of referral to paediatric services. This report is of a family of seven siblings all of whom have suffered breath-holding spells, including three who developed breath-holding spells within the neonatal period, with the other four developing them at 3-4 months of age. All of the children have on occasions exhibited convulsive activity at the termination of the episode. All had normal initial electroencephalogram's (EEG) and one had centrotemporal spikes on his EEG when repeated at age 6 years. Anticonvulsant therapy resulted in a reduced frequency of breath-holding spells. The epidemiology, pathophysiology and therapy of breath-holding spells is discussed with reference to this unique family. This report gives further credence to the notion that there often may be a familial predisposition to breath-holding spells. PMID- 1605980 TI - Aluminium absorption and antacid therapy in infancy. AB - The aim of this study was to determine whether infants absorb aluminium from antacid therapy. The study was conducted at Torrens House, a service provided by Child and Adolescent Health Services (CAFHS) for feeding and settling problems. Over an 11 week period, all patients receiving antacid therapy were studied. Patients not receiving antacids but of similar age acted as controls. Plasma and urine levels of aluminium were measured. The 15 infants receiving antacids had higher aluminium levels than the 17 controls (plasma 3.3 +/- 2.2 mumol/L vs 1.5 +/- 1.5 mumol/L, P less than 0.01; urine 25.1 +/- 27.6 mumol/L vs 1.1 +/- 1.8 mumol/L, P less than 0.004). The response was variable with 50% of infants receiving antacids recording plasma aluminium levels previously associated with toxicity in patients with renal failure after chronic exposure to aluminium. We conclude that infants absorb aluminium from antacids and suggest that patients receiving have their plasma levels monitored to identify those at possible risk of toxicity. PMID- 1605981 TI - Tachyarrhythmia, cardiac rhabdomyomata and fetal hydrops in a premature infant with tuberous sclerosis. AB - An hydropic infant was delivered at 32 weeks gestation by emergency Caesarean section for acute polyhydramnios. A diagnosis of cardiac rhabdomyomata was made on echocardiography. The baby survived 10 days, during which time repeated episodes of supraventricular tachycardia occurred. She eventually died of cardiac failure following an episode of septicaemia, convulsions and aspiration pneumonia. Necropsy showed multiple cardiac rhabdomyomata and numerous cerebral germinal layer and periventricular white matter nodules. This case stresses the importance of clinical investigations and perinatal necropsy in non-immune hydrops fetalis (NIHF) in determining the causes of clinical presentation and the underlying pathology. PMID- 1605982 TI - Acquired amegakaryocytic thrombocytopaenia in a child. AB - A boy aged 5 years is described with amegakaryocytic thrombocytopaenia, which was associated with defective granulopoiesis and erythropoiesis, but did not evolve into marrow aplasia. Marrow cultures confirmed the presence of abnormalities in each of the haemopoietic lineages and identified defective maturation of megakaryocytic precursors. The was no evidence of a humoral inhibitor of megakaryopoiesis. The patient's blood cell counts responded to treatment with oxymetholone. PMID- 1605984 TI - Anthropometry and obesity in myelomeningocele. PMID- 1605983 TI - Antineutrophil cytoplasmic antibody and gallium lung scintiscan in usual interstitial pneumonitis. AB - A 2 year old Chinese boy was reported in whom there was an association between usual interstitial pneumonitis (UIP) and serum antineutrophil cytoplasmic antibody of the classical cytoplasmic type (cANCA). The concentration of cANCA reflected disease activity and decreased during a 6-week course of prednisolone. The gallium lung scintiscan index correlated with his disease activity. Both the serum cANCA concentration and the gallium lung scan could be used to monitor responses to treatment in this patient with UIP. PMID- 1605985 TI - Cot death. PMID- 1605986 TI - Resource allocation in contemporary paediatrics. PMID- 1605987 TI - Writing for publication: it's a matter of personal style. AB - One of the best ways a nurse practitioner can make a lasting contribution is through the published word. A nurse writer publishes to inform, instruct, challenge, and inspire. This sharing of ideas is critical for professional growth and visibility. The writing process may appear at first glance to be difficult, yet the tips and techniques described in this article demonstrate that writing is a craft which can be learned. Although the process that results in a final, published manuscript may, at times, appear lengthy, the approach to preparing a manuscript is simple, requiring a modicum of skill and a strong desire to share knowledge. PMID- 1605988 TI - Factors discriminating between genuine stress and mixed incontinence. AB - Nurse practitioners (NP) are often confronted with female clients who describe various types of urine loss symptoms. To establish an accurate diagnosis and therapeutic intervention, it is important for the NP to identify the etiology of the urine loss complaint. The purpose of the study is to compare symptoms and physical findings that differentiate between the urodynamic diagnoses of genuine stress incontinence (GSI) and mixed incontinence (MI) in 135 clinical trial subjects: 123 diagnosed as GSI and 12 as MI. These subjects participated in a randomized controlled clinical trial to investigate the efficacy of biofeedback and pelvic floor exercises for incontinence treatment. Data were analyzed for significant differences between these two groups on urologic and gynecologic symptoms, pelvic muscle relaxation, vaginal mucosa, vaginal electromyograph readings, urodynamic parameters, and quantified measure of urine loss. One-way analysis of variance (ANOVA) showed significant difference in nocturnal and diurnal voidings and urine loss immediately after sensing the urge to void in the MI and GSI subjects. Chi-square analyses found a significantly decreased incidence of poor vaginal tone and atrophic vaginal mucosa in the MI group as compared to the GSI group. The MI group also lost significantly more urine than did the GSI group on the hand wash maneuver of the perineal pad test. Although the sample size of MI subjects was small, these results show that a noninvasive history and physical examination can differentiate between urologic diagnoses. This approach provides a cost-effective expedient protocol to aid the NP in establishing a differential diagnosis between genuine stress and mixed incontinence. PMID- 1605989 TI - Adult children of alcoholics. AB - Adult children of alcoholics are increasingly recognized as a population facing greater risk for developing emotional and physical problems. This article describes characteristics of adult children of alcoholics and presents a method for identifying those most at risk. Implications for practice are also discussed. PMID- 1605990 TI - The games of politics. AB - Understanding and learning to play the games of politics can increase the political efficiency of nurse practitioners (NPs) and assist them in advancing their roles and functioning in the crowded health care arena. One framework that can be applied to the political process is Allison's Governmental Political Model. Allison's model approaches the process of politics as competitive games. This article presents Allison's political model and demonstrates how understanding and learning to play political games has potential to promote NP political effectiveness. PMID- 1605991 TI - Screening for ovarian cancer. PMID- 1605992 TI - Medicare Physician Payment Reform: implications for nurse practitioners. AB - In January 1992, the federal government implemented a package of physician payment reforms for use in the Medicare program. Among these reforms is a resource-based fee schedule that replaces the customary, prevailing, and reasonable (CPR) method of payment that has been used since Medicare's inception. This article describes the recommendations of the Physician Payment Review Commission, a Congressional advisory group, concerning the implications of the resource-based fee schedule on nurse practitioners and other non-physician practitioners. Absent changes in current law, services provided by nurse practitioners will be paid based on the same formulas that were used under CPR. This author advises that these payment formulas be revised to reflect the differences in resource costs borne by physicians and nonphysicians. Furthermore, revisions to the payment formulas should be made in the near future before the Medicare fee schedule and the rules governing its use are adopted by other public (e.g., Medicaid) and private payers. PMID- 1605993 TI - Hyperthyroidism: a comprehensive review. AB - Hyperthyroidism is an endocrine disorder encountered in adult primary care clinics. This article reviews normal thyroid physiology as well as the pathophysiology, diagnosis, clinical signs and symptoms, and diagnostic tests and treatment for the most common clinical hyperthyroid entities. Current research is also discussed as it relates to clinical practice. PMID- 1605994 TI - Elder abuse and neglect: a relationship to health characteristics. AB - Elder abuse is a complex problem that has received increasing attention in the social science literature and the media during the past 10 years. This descriptive study addresses the relationship between the type of abuse experienced and the demographic and health characteristics of elderly, abused individuals living in the community. Demographic data from this retrospective case review identify the most common victim of abuse as an elderly, widowed woman with some degree of chronic illness. The results also indicate that dependency needs of the individuals, including such health problems as mental confusion, immobility, and need for assistance with hygiene, are most often associated with neglect, a common form of maltreatment of the elderly. The recognition of risk factors for elder abuse or neglect can assist nurse practitioners in developing appropriate interventions for this serious health problem. PMID- 1605995 TI - Assessment and initial management of infertility. AB - The rate of infertility is increasing in this country. Primary and secondary infertility affect almost 25% of all couples of childbearing age. Because of the large number of couples affected by infertility, primary care nurse practitioners (NPs) should expect to encounter this problem within their practice. Initial assessment, diagnosis, and management, as well as education, consultation, and support, are well within NPs' scope of practice. This article details the initial history, physical examination, and tests that might precede referral to an infertility specialist. The psychosocial aspect of infertility is also addressed. PMID- 1605996 TI - Self-management of recovery: implications for nursing practice. AB - This article describes and discusses differences in responses to a 60-item survey instrument, the Carolina Self-Regulation Inventory (CSRI) from a selected sample of university faculty and staff. The CSRI was designed to measure the types of self-regulation strategies (SRS) individuals use to facilitate their recovery from illness episodes. When the CSRI was developed, 1,306 university employees participated in the survey. Four hundred eighty (36%) employees classified themselves as faculty; 346 (26%), staff; 418 (32%), midlevel administrators; and 62 (6%), blue-collar workers. This report focuses on the differences between the faculty and staff groups in the survey. Analysis revealed that the staff used a variety of strategies and had higher statistically significant means on the following CSRI subscales: visualization (t = 2.53, P less than .01), self-talk (t = 6.801, P less than .001), and external attention deployment strategies (t = 4.08, P less than .001). No significant differences were found between faculty and staff in the use of exercise and physical activity or interactive self regulation strategies. Higher-educated faculty women tended to use fewer SRS when compared with female staff (F = 4.70; df = 8.819; P = .0009). Faculty women were similar to faculty men in their use of SRS. Female staff used significantly more SRS when compared with faculty of both genders and male staff (t = 2.81, P = .05). Nursing implications of self-regulation nursing assessments are discussed in terms of nursing interventions and need for more research. PMID- 1605997 TI - Pressure ulcers, Part 1: Prevention strategies. AB - Pressure ulcers are a costly health concern. Many can be prevented by conscientious, vigorous nursing care. The nurse practitioner (NP) is an ideal professional to direct preventive care and to manage the treatment of ulcers. This article reviews the multiple risk factors and dynamics involved in the development of pressure ulcers, and preventive measures that can be implemented. The role of an NP related to pressure ulcer prevention and specific NP interventions are discussed. PMID- 1605998 TI - A comparative analysis of nurse practitioners with and without prescriptive authority. AB - This article reports findings from a national random sample of nurse practitioners (NPs) who were actively practicing in adult primary care settings during 1986. An analysis of their demographic and practice characteristics revealed a statistically significant association between certain characteristics and the NPs' prescribing status. Nurse practitioners with prescriptive authority had more years of experience and were more likely to practice in rural or suburban areas and work in nongroup settings than NPs without prescriptive authority. These findings suggest that giving NPs' prescriptive authority may be an enabling factor that supports NP practice in medically underserved locations. PMID- 1605999 TI - Chondromalacia patella. PMID- 1606000 TI - Have you talked with your legislator recently? PMID- 1606001 TI - The inside story: a simulation game on ethical, legal, and political decision making in health policy for nurse practitioners. AB - This game can be conducted with as many as 50 and as few as 15 players. The optimum size includes 4-5 Board members and 4-6 participants in each of the four small-group scenarios. The game takes about 11/2-2 hours to play. This includes a break between Part I and Part II. Existing state and national laws and policies are used in the game so that participants may understand their effects and limitations. The game has no winners or losers. Everyone gains if the decision markers are able to consider the needs of the individuals and the needs of the public, though some individuals may or may not benefit as much as others. This, however, is reality and is inherent in the policy-making process. In primary care, nurse practitioners (NPs) have a crucial responsibility to weigh the impact of their decisions on their clients and the community. The "Inside Story" integrates recommended NP curriculum content such as ethical decision making and health policy into a creative and powerful educational experience. This simulation game could be adapted for other topics with ethical, legal, and political implications such as issues regarding allocation of scarce resources. It could be played among students or professionals from many disciplines as part of their curriculum or in a continuing education offering. PMID- 1606003 TI - Surgical wounds. Wound dehiscence: causes and care. PMID- 1606002 TI - Hospital equipment. Hospital seating and pressure areas. PMID- 1606004 TI - Tissue viability. Some legal issues in wound management. PMID- 1606006 TI - Community nurses. 'Buy-in nurses?'. PMID- 1606005 TI - World malaria situation in 1990. Part II. PMID- 1606007 TI - Parent and child views of an ENT ward. AB - This is a descriptive field study concerning the reported experience of parents and their children who were admitted for tonsillectomy or adenoidectomy to a northern hospital. Twenty parents and 20 children were asked to record the five most liked and disliked aspects of being in hospital. It was found that staff were considered salient and evaluated positively by both parents and children. Children found the most negative experience to be the postoperative period. There was no evidence of preoperative anxiety. It is recommended that further research should focus on ameliorating the negative experience of the postoperative period for children. PMID- 1606008 TI - A psychodrama group for health workers. AB - Although much has been written about psychodrama as a therapeutic and educational method with patients, there is little evidence of its effectiveness as an activity for professional clinicians. The authors describe how the basic elements, phases and techniques of psychodrama have been used with groups of health workers to improve their clinical performance and personal life. The therapy has important applications in helping staff come to terms with the emotional stresses of their work with patients. PMID- 1606009 TI - Nurse training needs in AIDS counselling. AB - Twenty-one people involved in AIDS counselling or nurse education on AIDS were interviewed using a semi-structured process involving key questions. The interviews were transcribed directly onto a lap-top computer, then entered into a free-form database computer program for analysis. The findings, although non generalisable, indicate that counselling is seen as a necessary part of the support services offered to people with HIV or AIDS, but is not necessarily a task suitable for nurses. AIDS counsellors were identified as the main source of psychosocial help for people with HIV or AIDS, whose main concerns were perceived as being fear of stigmatisation, poor health and dying. The issues of whether or not to train nurses as AIDS counsellors, and how to train them, require further study. PMID- 1606010 TI - Royal Liverpool HIV letter well planned. PMID- 1606011 TI - Community care changes: stranded at the drive out. PMID- 1606013 TI - Interviews: urbane griller tactics. PMID- 1606012 TI - Education: return of the robot tutors. PMID- 1606014 TI - Quality assurance: equality assured? PMID- 1606015 TI - Community nursing: nurses' districts invaded. PMID- 1606016 TI - NHS changes: I'm waiting for the scan. PMID- 1606017 TI - A day in the life: just like on telly. PMID- 1606018 TI - The presumptive R7 cell of the developing Drosophila eye receives positional information independent of sevenless, boss and sina. AB - Studies on the development of the R7 photoreceptor in the Drosophila eye thus far have identified three genes that specifically affect this cell: sevenless, boss and sina. In each of these mutants the R7 precursor develops instead as the equatorial cone cell (EQC). We have isolated an enhancer trap line, H214, in which beta-galactosidase is primarily expressed in the R7 cell throughout its development. In mutations of sevenless, boss and sina, expression in H214 is initially reduced although still present in the R7 precursor and persists in the EQC into which it develops. The EQC in wild type never expresses lacZ in H214. This result is in contrast to that seen with other enhancer trap lines that display expression in R7, and indicates that some aspect of R7 differentiation is independent of the genetic pathway(s) involving sevenless, boss and sina. PMID- 1606019 TI - Epithelial polarity and cell separation in the neoplastic l(1)dlg-1 mutant of Drosophila. AB - Lethal (1) discs-large-1 [l(1)dlg-1] is a non-epithelial overgrowth or neoplastic mutant of Drosophila, which results in tumor-like imaginal discs and enlarged larvae that never pupariate. In an ultrastructural analysis we found that the wing discs develop convoluted monolayers of epithelial cells characterized by well-defined apical-basal polarity and that these layered cells secrete large amounts of basement membrane material. Immuno-EM indicates that Drosophila laminin and collagen are components of this matrix. Late in development clusters or 'rosettes' of separated cells lacking cell-cell junctions and apical-basal polarity form. In in vitro culture experiments l(1)dlg-1 wing discs did not respond to a pulse of exogenous ecdysone by secreting cuticle or losing basement membrane as normal discs do. Our observations are consistent with the hypothesis that cell-cell interaction and communication is required for termination of disc cell proliferation, which must occur prior to a cellular response to ecdysone. PMID- 1606020 TI - Molecular cloning, expression and in vitro functional characterization of Myb related proteins in Xenopus. AB - Two cDNAs encoding Myb-related proteins have been cloned from Xenopus laevis and they have been termed Xmyb1 and Xmyb2. The Xmyb1 cDNA clone codes for an open reading frame of 733 amino acids and exhibits a high degree of similarity over the entire predicted protein sequence with the human B-Myb protein. Xmyb2 is a partial cDNA clone encoding three copies of amino-terminal tandem repeat elements typical for the Myb DNA-binding domain. The predicted protein sequence is most closely related to the human A-Myb gene product. In vitro translation of two deletion mutants of Xmyb1, truncated in the 3'-portion of the open reading frame, results in protein products which cross-react with polyvalent as well as monoclonal antibodies directed against the human c-Myb protein. The same two XMyb1 proteins, which both contain the complete set of aminoterminal repeats, specifically bind to the c-Myb-specific DNA binding sequence as evidenced by electrophoretic mobility shift analysis in vitro. RNA expression profiles of Xmyb1 and -2 are very different from each other; Xmyb1 is present throughout oogenesis and early Xenopus embryogenesis; in adult tissue it is primarily detected in blood. In contrast, Xmyb2 is expressed at only very low levels during oogenesis, not detectable in embryonic RNA preparations, and in adult tissue it is predominantly expressed in testis, with only a very low level seen in blood. PMID- 1606021 TI - The yemanuclein-alpha: a new Drosophila DNA binding protein specific for the oocyte nucleus. AB - The Drosophila yG 4.5 gene (now called yemanuclein-alpha gene), which maps at 98F, is a member of the yema gene cluster isolated in a search for differentially expressed maternal genes. The yemanuclein-alpha transcript (formerly yT 4.5) is specifically expressed in the female germ cells at early oogenic stages and displays a graded distribution along the antero-posterior axis of the oocyte. These provocative features are reminiscent of that of K10, bicoid and Bicaudal-D gene transcripts and lead us to hypothesize that the yemanuclein-alpha gene plays a key role in egg organization. We show in the present work that the yemanuclein alpha is a nuclear protein highly specific for the oocyte nucleus. The sequence analysis of the 5696 bp EcoRI fragment containing the yemanuclein-alpha gene, and of 5 overlapping cDNAs, reveals a 3006 nucleotides long open reading frame (ORF) flanked by long untranslated 5' and 3' sequences. This ORF predicts a 109,215 kDa protein which is basic (pHi: 8.57), and serine rich (12.08%). It contains a 40 amino acid acidic domain in the first third of the protein with a potential alpha helix organization; this domain has some similarity with the nucleolin acidic domain. Parts of the yemanuclein-alpha sequence are likely to form secondary structures known to interact with DNA. We demonstrate the DNA binding activity of the yemanuclein-alpha by affinity chromatography experiments. Our data indicate that the yemanuclein-alpha shares some of the features which are characteristic of genuine transcriptional activators. PMID- 1606022 TI - Drosophila salivary glands exhibit a regional reprogramming of gene expression during the third larval instar. AB - In D. virilis salivary glands transcripts of two early gland protein genes, Egp-1 and Egp-2, which encode putative secretory proteins, accumulate in all cells from the first to mid third larval instar. Subsequently the transcripts disappear from the cytoplasm of the corpus cells, but not from their nuclei, where they accumulate at the chromosomal site of their synthesis. In the collum cells, however, Egp-transcripts continue to be detectable in the cytoplasm until the end of larval life. In the salivary glands of transgenic D. melanogaster the presence of a Egp-1/lacZ fusion protein shows the same regional shift as the cytoplasmic Egp-transcripts in D. virilis. We predict that the expression of Egp-genes is related to an early secretory function of the larval salivary glands which is executed by all cells during earlier larval stages but becomes restricted exclusively to the collum cells during the third larval instar. PMID- 1606023 TI - Peter Holland: a pioneer of occupational medicine. AB - The earliest recorded occupational health service in this country was that established in a cotton spinning factory at Quarry Bank Mill in Cheshire. The mill was built in 1784 by Samuel Greg and his partners. They employed local labour and also some parish apprentices. Happily, Samuel Greg was a good christian and, having created a modern factory and a model village with a church and a school, he was equally concerned for the physical welfare of his employees. Accordingly, he appointed a doctor to make pre-employment examinations of the apprentices and to visit regularly to deal with the health problems of a community of some 400 people. The man he chose was Peter Holland of Sandlebridge, who had served his medical apprenticeship under Dr Charles White of Manchester. The first record of the employment of a doctor was in 1796, but from 1804 to 1845 (doubtless in response to the early factory legislation) each visit of the doctor was entered in a day book with either an indication of fitness to work or details of the treatment required. The complete record consists of two hardback foolscap notebooks that provide a fascinating insight into the medical practice of the times when the industrial revolution was just getting under way. One of the more interesting features is the preservation of medical secrecy. Dr Holland made his comments on the case in shorthand and his instructions in longhand. By a fortunate coincidence the key to the shorthand was discovered and this has now been largely transcribed. Although much of the content of the diaries is the day by day practice of medicine at the time, there are many illuminating glimpses of the early practice of occupational medicine. PMID- 1606024 TI - Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites. AB - The relation between exposure to As2O3 fumes and dust, and the urinary excretion of inorganic arsenic metabolites (monomethylarsonic acid, dimethylarsinic acid, unchanged inorganic arsenic) has been studied in 18 workers from a sulphuric acid producing plant. The concentration of arsenic in the breathing zone of each worker was measured during five consecutive days and urine samples were obtained after one shift and before the next. The collection efficiency of the air sampling system exceeded 95%. The time weighted average exposure (TWA) concentrations of As2O3 ranged from 6 to 502 micrograms As/m3 and were log normally distributed. Although exposure probably occurred by ingestion as well as inhalation, statistically significant correlations (log scales) were found between airborne TWA of As2O3 and the inorganic arsenic metabolites in urine collected immediately after the shift, or just before the next shift. For a TWA of 50 micrograms As/m3, the mean concentration of the sum of the three inorganic arsenic metabolites in a postshift urine sample amounted to about 55 micrograms arsenic/g creatinine (95% confidence interval (95% CI) 47-62). Higher estimates of urinary arsenic reported by other authors are probably due either to the influence of dietary organoarsenicals when total arsenic is measured in urine or to a low retention efficiency of the air sampling system for As2O3 in the vapour phase. PMID- 1606025 TI - Renal and immunological effects of occupational exposure to inorganic mercury. AB - Seven parameters of renal dysfunction (urinary excretion of albumin, orosomucoid, beta 2-microglobulin, N-acetyl-beta-glucosaminidase (NAG), and copper; serum creatinine concentration, and relative clearance of beta 2-microglobulin) were examined in a group of chloralkali workers exposed to mercury vapour (n = 89) and in an unexposed control group (n = 75). Serum concentrations of immunoglobulins (IgA, IgG, IgM) and auto-antibodies towards glomeruli and other tissues were also determined. The parameters examined were compared between the two groups and related to different exposure parameters. In the chloralkali group median blood mercury concentration (B-Hg) was 55 nmol/l, serum mercury (S-Hg) 45 nmol/l, and urine mercury concentration (U-Hg) 14.3 nmol/mmol creatinine (25.4 micrograms/g creatinine). Corresponding concentrations for the control group were 15 nmol/l, 4 nmol/l, and 1.1 nmol/mmol creatinine (1.9 micrograms/g creatinine) respectively. None of the parameters of renal dysfunction differed significantly between the two groups, but there was a tendency to increased excretion of NAG in the exposed group compared with the controls. Also, a statistically significant relation existed between U-Hg and U-NAG (p less than 0.001). Serum immunoglobulin concentrations did not differ between the groups, and serum titres of autoantibodies (including antiglomerular basement membrane and antilaminin antibodies) were low in both groups. Thus the results gave no evidence of glomerular damage or of a tubular reabsorption defect at the current relatively low exposures. The findings still indicate slight, dose related tubular cell damage in the mercury exposed group. There were no signs of a mercury induced effect on the immune system. PMID- 1606026 TI - Neuroendocrine effects in printing workers exposed to toluene. AB - The effect of exposure to toluene on plasma concentrations of testosterone, prolactin, luteinising (LH) and follicle stimulating (FSH) hormones was investigated in 47 rotogravure printers (time weighted average air toluene below 80 ppm; blood toluene concentration post-shift 0.19-7.99 mumol/l) and compared with a reference group. Increasing exposure concentrations of toluene (concentrations less than 5 to greater than 45 ppm) were significantly associated with decreasing plasma concentrations of LH (tau = -0.21, p = 0.003) and testosterone (tau = -0.25, p = 0.02). No correlation was found between cumulative exposure (ppm x years) and plasma hormone concentrations. The associations with exposure were present even when nine printers with heavy alcohol consumption were excluded. The study indicates an effect of low toluene exposure on the hypothalamus-pituitary axis, with a secondary decrease in testosterone secretion. PMID- 1606027 TI - Diagnoses of alcohol abuse and other neuropsychiatric disorders among house painters compared with house carpenters. AB - The incidence of alcoholism and the incidence of other neuropsychiatric diagnoses were compared between the 767 house painters and the 1212 house carpenters, born in 1925 or later, who were members of the Stockholm branches of their respective trade unions in 1965 and who had been members for at least 10 years before 1970. Four different outcome registers were used: (1) the alcohol crime register, which contained all persons who had broken any law regulating the handling and consumption of alcohol (follow up period 1972-6). (2) The register of diagnoses at early retirement (follow up period 1971-84). (3) The register of diagnoses at discharge from inpatient psychiatric care (follow up period 1968-83). (4) The register of causes of death (follow up period 1965-86). Exposures to solvents and consumption of alcohol were evaluated by interviews with samples of the cohorts. A high average cumulative exposure to solvents was found among the painters. The mean consumption of alcohol was similar in the two cohorts. The incidence of diagnoses of neuropsychiatric disorders was higher in painters than in carpenters in all registers. Alcoholism was the most common neuropsychiatric disorder diagnosed and showed the highest relative risk. The excess of alcoholism among the painters was, however, due singularly to painters who had several registrations in the alcohol crime register or diagnoses of alcoholism in multiple registers. Thus the study implies that excessive alcohol consumption or severe damage due to alcohol, or both, but not less severe problems, were more common in painters than in carpenters. This suggests an interaction between exposure to solvents and intake of alcohol causing an increase in diagnosis of alcoholism among painters. PMID- 1606029 TI - Signs of alveolar inflammation in non-smoking Swedish wood trimmers. AB - Wood trimmers are periodically exposed to mould and may develop extrinsic allergic alveolitis (EAA). To investigate if there were any signs of EAA in wood trimmers with low exposure, 19 non-smoking wood trimmers underwent bronchoalveolar lavage (BAL), spirometry, and measurement of diffusion capacity (TLCO). The group was subdivided into those with (n = 9) and without serological antibodies against mould. In 14 workers the TLCO was measured both at the beginning and at the end of a week at work. Twenty five healthy non-smokers served as BAL controls and 19 healthy non-smokers as lung function controls. The median exposure of total dust was well below the Swedish threshold value, and the exposure of mould and bacteria was also low. The cell concentrations and the proportions of the various alveolar cells did not differ between the groups. The concentrations of the soluble components albumin, fibronectin, and hyaluronan were, however, significantly increased (p less than 0.001 for all) in the workers. No difference was found in lung function between the workers and the controls, and the TLCO was not impaired during a week at work. The groups of seropositive and seronegative workers did not differ in any of these parameters. The results are interpreted as a low intensity alveolar inflammation. The presence of precipitating antibodies against mould did not predict any greater risk of developing a more intense inflammation. Analysis of soluble non-cellular BAL components seems to reflect a discrete ongoing alveolar inflammation better than cell counts only. PMID- 1606028 TI - Reduction of airborne allergenic urinary proteins from laboratory rats. AB - Allergy and asthma caused by proteins of laboratory animals, particularly rats and mice, are the most important occupational health hazards for the scientists and technicians who work with such animals. The influence of different cage litters, cage design, and stock density on measured rat urinary aeroallergen (RUA) concentrations has been examined in a room housing male rats, to determine practical means to reduce allergen concentration in animal laboratories. Eight hour static air samples were taken at 2 1/min and the RUA concentrations measured by radioallergosorbent test (RAST) inhibition. High RUA concentrations occurred when the animals were housed on wood based, contact litter (geometric mean (GM) sawdust 7.79 micrograms/m3; woodchip 6.16 micrograms/m3). The use of noncontact absorbent pads was associated with a significant decrease in RUA concentrations (GM 2.47 micrograms/m3; p less than 0.0001). Rat urinary aeroallergen concentrations fell more than fourfold when the animals were housed on woodbased, contact litter in filter top cages rather than conventional open top cages (GM filter top 0.33 micrograms/m3; open top 1.43 micrograms/m3; p less than 0.0001). The number of rats (stock density) strongly influenced the RUA concentration and a linear relation was found between the log(e) allergen concentration and stock density under these study conditions. The measurement of airborne particle size on cleaning out days showed that all litter types generated similar sized particles: more than 80% of the RUA was carried on particles larger than 8 microns in diameter for all litter types. The findings suggest that the exposure of animal husbandry personnel to RUA may be substantially reduced by the avoidance of contact litter, the use of filter top cages (where suitable), and by keeping stock density to a minimum. PMID- 1606030 TI - Respiratory symptoms and ventilatory capacity in swine confinement workers. AB - A group of 59 workers (41 men and 18 women) employed in swine confinement areas was studied to assess the presence of acute and chronic respiratory symptoms and the prevalence of abnormalities in ventilatory function. A control group of 46 (31 men and 15 women) unexposed workers was studied for the prevalence of chronic respiratory symptoms. For both male and female swine confinement workers complaints of chronic cough, dyspnoea, and chest tightness were significantly more frequent than among control workers. Male workers also complained more of chronic phlegm. Male swine confinement workers who were smokers had significantly higher prevalences of chronic cough, chronic phlegm, and chronic bronchitis than male non-smoking swine confinement workers. The frequency of acute symptoms associated with the workshift was high among the swine confinement workers with more than half of the workers complaining of cough and dyspnoea associated with work. Significant acute across shift reductions in lung function occurred in swine confinement workers, being largest for FEF25. All Monday preshift ventilatory capacity measurements in male confinement workers were significantly lower than predicted values; FVC and FEV1 were found to be lower than predicted values for women. The data indicate that exposure in swine confinement buildings is associated with the development of acute and chronic respiratory symptoms and impairment of lung function. Smoking appears to aggravate these changes. PMID- 1606031 TI - Small airways dysfunction among non-smoking shipyard arc welders. AB - Increased volume of trapped gas (VTG), indicating small airways dysfunction, was found among 14 never smoking non-atopic welders who had worked for 10-31 (mean 22) years in their occupation. Spirometry and nitrogen wash out data were compared with those from a reference group of 14 never smoking men not exposed to welding. A methacholine provocation test was carried out. The effect was measured by change in forced expiratory volume in one second (FEV1) and VTG. The maximum decrease in FEV1 after inhalation of methacholine was 6% in welders and 2% among referents. Before provocation VTG and VTG total lung capacity (TLC) was higher among welders (127 ml v 98 ml and 1.76% v 1.38%). The increase in VTG and VTG/TLC was higher in welders after inhalation of methacholine at concentrations of 0.001% to 2% and remained increased after inhalation of salbutamol. The differences indicate small airways disease among shipyard welders. PMID- 1606032 TI - Forced expiratory volume in one second: why dichotomise? PMID- 1606033 TI - Pleural effusion in silicosis of the lung. PMID- 1606035 TI - Prediction of mesothelioma, lung cancer, and asbestosis in former Wittenoom asbestos workers. PMID- 1606034 TI - Asbestos and cancer: history and public policy. PMID- 1606036 TI - Non-occupational pneumoconiosis at high altitude villages in central Ladakh. PMID- 1606037 TI - A case-control study of lung cancer in a cohort of workers potentially exposed to slag wool fibres. PMID- 1606038 TI - Inhalation fever: a proposed unifying term for febrile reactions to inhalation of noxious substances. PMID- 1606039 TI - The methyltrienolone binding protein of JEG-3 cells and human placenta is localized within the nucleus and is tightly associated with chromatin. AB - Human placenta contains the methyltrienolone binding protein (MTBP), an androgen binding protein which is distinct from the androgen receptor. This study demonstrates that the human choriocarcinoma cell line (JEG-3) also contains the MTBP and that in both human placenta and JEG-3 cells the MTBP is located exclusively in the nucleus and in particular is associated with DNase 1 resistant chromatin. PMID- 1606040 TI - Contribution of aromatase to the deoxyribonucleic acid synthesis of MCF-7 human breast cancer cells and its suppression by aromatase inhibitors. AB - We have studied the effects of various steroids on DNA synthesis in MCF-7 human breast carcinoma cells, which have aromatase activity and which exert an oestrogen receptor-mediated growth, to assess the significance of intracellular aromatase on growth stimulation as well as inhibition by aromatase inhibitors. The cells were cultured for 96 h in phenol red-free medium containing 10% charcoal-treated fetal bovine serum and test reagents and pulse-labelled with [3H]thymidine. Physiological concentrations of oestradiol, oestrone, testosterone (T) and androstenedione (AD) stimulated thymidine incorporation. However, oestrone-sulphate and dihydrotestosterone (DHT) only stimulated at concentrations greater than the physiological levels. T and DHT stimulation was blocked by tamoxifen, but not by cyproterone acetate, suggesting that the stimulation was mediated via the oestrogen receptor but not by the androgen receptor. Stimulation by T and AD was reduced by aminoglutethimide and 14 alpha-hydroxy-4-androstene 3,6,17-trione, both of which inhibit aromatase activity, however, stimulation by nonaromatizable DHT was not reduced by the inhibitors, suggesting that androgens were converted by the intracellular aromatase to oestrogens which stimulated the thymidine incorporation. It is suggested that intracellular aromatase significantly contributes to the stimulation of DNA synthesis and that aromatase inhibitors suppress the stimulation. PMID- 1606041 TI - Inhibition mechanism of reconstituted cytochrome P-450scc-linked monooxygenase system by antimycotic reagents and other inhibitors. AB - The effects of various antimycotic reagents and some other reagents on a cytochrome P-450-linked monooxygenase system were investigated with respect to the activities of NADPH-ferricyanide reductase. NADPH-cytochrome c reductase of NADPH-adreno-ferredoxin reductase from NADPH to cytochrome c via adreno ferredoxin, NADPH-cytochrome P-450-phenylisocyanide complex reductase, and the cholesterol side chain cleavage of the cytochrome P-450scc-linked monooxygenase system. No reagents inhibited the NADPH-ferricyanide reductase activity. Only cloconazole inhibited about 50% of NADPH-cytochrome c reductase activity. Cloconazole, econazole, clotrimazole, etomidate and ketoconazole inhibited both NADPH-cytochrome P-450-phenylisocyanide complex reductase and the side chain cleavage activity of cholesterol of the cytochrome P-450scc-linked monooxygenase system. Cloconazole, econazole, etomidate and ketoconazole behaved like non competitive inhibitors for NADPH-cytochrome P-450-phenylisocyanide reductase activities and their Ki values were 10(-4)-10(-6) M. Cloconazole was a non competitive inhibitor of NADPH-cytochrome c reductase and its Ki value was 8.3 x 10(-4) M. Cloconazole, clotrimazole, econazole, etomidate, ketoconazole and mitotane completely inhibited the side chain cleavage activity of cholesterol. PMID- 1606042 TI - Effect of dexamethasone on nucleolar casein kinase II activity and phosphorylation of nucleolin in lymphosarcoma P1798 cells. AB - Ribosomal RNA (rRNA) synthesis in murine P1798 lymphosarcoma cells is reversibly inhibited by glucocorticoids. The effects of dexamethasone upon nucleolin phosphorylation and upon the amount and activity of casein kinase II have been examined. P1798 cells were exposed to 0.1 microM dexamethasone for 36 h. Cells were labeled in vivo with [32P]orthophosphate followed by immunoprecipitation with anti-nucleolin antibody. Nucleolin phosphorylation was reduced by 60% in dexamethasone-treated cells. Nucleoli were isolated and labeled with [gamma 32P]ATP in vitro. Nucleolin protein was reduced to 40% of control in nuclei from dexamethasone-treated cells. Nucleolin phosphorylation was reduced to 20% of control. Nucleolar casein kinase II activity and protein were also reduced (30 55% and 35-50% of control, respectively) by treatment with dexamethasone. Cycloheximide (10 micrograms/ml for 3 h) reduced the amount and activity of casein kinase II, but did not cause a decrease in nucleolin protein. These observations are discussed relative to the hypothesis that glucocorticoids regulate the amount or activity of proteins of short biological half-life that are involved in the regulation of rRNA synthesis. PMID- 1606043 TI - 4-pregnene-3-one-20 beta-carboxaldehyde: a potent inhibitor of 17 alpha hydroxylase/C17,20-lyase and of 5 alpha-reductase. AB - The pregnene derivative, 4-pregnene-3-one-20 beta-carboxaldehyde (22-A) was evaluated as an inhibitor of 17 alpha-hydroxylase/C17,20-lyase in rat testicular microsomes and of 5 alpha-reductase in human prostatic homogenates. The effect of the compound in vivo was studied in adult male rats. The 22-A demonstrated potent and competitive inhibition of 17 alpha-hydroxylase and C17,20-lyase with Ki values 8.48 and 0.41 microM, respectively, significantly below the Km values for these two enzymes (33.75 and 4.55 microM). This compound also showed potent inhibition of 5 alpha-reductase with a Ki value of 15.6 nM (Km for this enzyme is 50 nM). By comparison, ketoconazole, a currently studied 17 alpha hydroxylase/C17,20-lyase inhibitor for the treatment of prostatic cancer, showed less potent inhibition of 17 alpha-hydroxylase (Ki 39.5 microM) and C17,20-lyase (Ki 3.6 microM) and did not inhibit 5 alpha-reductase. Progesterone which has been reported to inhibit the 17 alpha-hydroxylase/C17,20-lyase, did not significantly reduce the production of testosterone by rat testes in vitro in comparison to controls, while the same concentration of 22-A demonstrated a 42% reduction of testosterone biosynthesis. When the adult male rats were injected s.c. with 22-A at 50 mg/day/kg for a 2 week period, the testosterone concentrations in the rat sera were significantly lower than control values (P less than 0.05), whereas serum corticosterone levels did not change. These results suggest that 22-A is a selective potent inhibitor for 17 alpha hydroxylase and C17,20-lyase, but is more potent for the C17,20-lyase. The compound also inhibits 5 alpha-reductase, and therefore may reduce biosynthesis of testosterone and dihydrotestosterone effectively. Thus, 22-A may be useful in the treatment of problems associated with the androgen excess and prostatic cancer. PMID- 1606044 TI - Purification and properties of the 5 alpha-dihydrotestosterone 3 alpha(beta) hydroxysteroid dehydrogenase from human prostatic cytosol. AB - 5 alpha-Dihydrotestosterone 3 alpha(beta)-hydroxysteroid dehydrogenase [3 alpha(beta)-HSDH] [EC 1.1.1.50/EC 1.1.1.51] which catalyses the conversion of 5 alpha-dihydrotestosterone (5 alpha-DHT) to both 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol was purified to an apparent homogeneous state using cytosol of three human hyperplastic prostates by a 4-step purification procedure. After each purification step 3 alpha-HSDH activity was coincident with 3 beta-HSDH activity. On average, specific 3 alpha-HSDH activity was enriched 856-fold, specific 3 beta-HSDH activity 749-fold compared to human prostatic cytosol using anion exchange, hydrophobic interaction, gel filtration and affinity chromatography. Examination of the purified enzyme by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate (SDS) revealed a single protein band with silver staining. The molecular weight of the enzyme was estimated as 33 kDa by SDS-polyacrylamide gel electrophoresis and as 28 kDa by Sephacryl S-200 gel filtration indicating that the native 3 alpha(beta)-HSDH is a monomer. In the presence of the preferred co-factor, NADPH, the purified enzyme had a mean apparent Km for 5 alpha-DHT of 3.9 microM and a Vmax of 93.3 nmol (mg protein)-1 h-1 with regard to 3 alpha-HSDH activity, and a Km of 6.3 microM and a Vmax of 20.6 nmol (mg protein)-1 h-1 with regard to 3 beta-HSDH activity. PMID- 1606045 TI - Binding of estrogen-3-sulfates to stallion plasma and equine serum albumin. AB - The binding of estrone-3-sulfate (E1-3-S) and estradiol-3-sulfate (E2-3-S) to adult stallion plasma was determined and compared with the binding to equine serum albumin (ESA). On the ESA molecule, two binding sites for E1-3-S with an association constant of 1.3 x 10(5) M-1 and several sites of weaker affinity were found; the data for E2-3-S showed the existence of four binding sites of moderate affinity (1 x 10(5) M-1) and several sites of weaker affinity. The removal of albumin from the stallion plasma resulted in the absence of binding of E1-3-S or E2-3-S, whereas the removal of glycoproteins resulted in binding parameters similar to those obtained with whole plasma. These results indicate that ESA is the only estrogen sulfate binder in horse plasma. Under physiological conditions, 95% of E1-3-S was bound to ESA. PMID- 1606046 TI - Steroids involved with final oocyte maturation in the winter flounder. AB - A number of androgens and progestogens including 17 alpha,20 beta-dihydroxy-4 pregnen-3-one (17,20-P) were examined in female winter flounder as possible maturation inducing steroids (MIS). During final oocyte maturation serum levels of testosterone (T) and 17 beta-hydroxy-5 beta-androsten-3-one (5 beta-T) peaking at over 200 ng/ml and pregnenolone (PE) at 40 ng/ml were the predominant steroids found from each major group. High levels of T and 5 beta-T were correlated with oocyte stages characterized by germinal vesicle migration. Of the PEs measured, maximum serum levels of PE, 3 beta,17 alpha-hydroxy-5-pregnen-20-one (17-PE) and 3 beta,17 alpha, 20 beta-dihydroxy-5-pregnene (17,20-PE) were found during later oocytes stages associated with germinal vesicle breakdown. Levels of 17,20-P, an established MIS in most fish, were almost non-detectable (less than 0.1 ng/ml serum) in females throughout all stages of final oocyte maturation. Incubations of ovarian follicles in vitro with physiological concentrations of T and 5 beta-T indicated that these steroids could induce all stages of final oocyte maturation. Similar in vitro incubations showed that 17-PE and 17,20-PE were only effective on germinal vesicle breakdown. The principal conclusions are that T, 5 beta-T and the PEs can be considered as MISs in winter flounder and the PE pathway predominates during the final stages of oocyte maturation in winter flounder in contrast to progesterones which predominate in other fish species, mostly salmonids, studies to date. PMID- 1606047 TI - Estrogen platinum-diamine complexes: preparation of a non-steroidal estrogen platinum-diamine complex labeled with platinum-191 and a study of its binding to the estrogen receptor in vitro and its tissue distribution in vivo. AB - We have prepared in radiolabeled form (platinum-191) a non-steroidal estrogen platinum-diamine complex (Pt-diamine complex) that is reported to have selective cytostatic activity in estrogen receptor positive mouse mammary tumors. We then studied the interaction of this metal radiolabeled complex with the estrogen receptor in vitro and its distribution in immature rats in vivo. The radiolabeled complex was prepared by incubation of the non-steroidal estrogen diamine with [191Pt](II)Cl(-2)4 (t 1/2 = 2.96 days, sp. act. 7.54 Ci/mmol) in dimethylformamide (DMF)/H2O, followed by purification by HPLC. The final radiolabeled product coeluted with an authentic standard of the unlabeled Pt diamine complex, with a retention time distinct from those of the precursor diamine and chloroplatinate. In competitive radiometric receptor binding assays with rat uterine estrogen receptor, samples of the unlabeled diamine and Pt diamine complex have apparent binding affinities of 53 +/- 3% and 32 +/- 11%, respectively, relative to estradiol (RBA = 100% as standard). However, attempts to observe the binding of the 191Pt-diamine complex with the estrogen receptor were complicated by a very high level of non-receptor binding, an irreversible binding to proteins in the receptor preparation, and a degradation of the platinum complex that, in part, releases the diamine. As a result, it is difficult to be certain whether the binding affinity measured for the Pt-diamine complex in the competitive binding assays is due to the complex itself, or whether it arises from diamine released upon degradation of the complex. In tissue distribution studies in immature female rats, much of the 191Pt-diamine complex was deposited in the liver; there was no evidence of selective uptake of this compound by estrogen target tissues. Thus, it is not clear, from these studies, that the observed bioactivity of this complex arises from the interaction of the Pt complex or the diamine ligand with the estrogen receptor. PMID- 1606048 TI - Metabolism of 11-deoxycorticosterone by hamster adrenal mitochondria. AB - Metabolism of 11-deoxycorticosterone (DOC) by hamster adrenal mitochondria gives 19-hydroxy-DOC and corticosterone (via 11-hydroxylation) in approximately equal yields. The ratio of 19- to 11-hydroxylation was invariant with changes in concentration of substrate or a competitive inhibitor. It is most likely, therefore, that a single 11,19-hydroxylase catalyzes both oxidations. Both primary products are further oxidized to the corresponding carbonyl analogs, 19 oxo-DOC and 11-dehydrocorticosterone, at rates that are approx. 20% of their rates of formation. The oxidation of 11-dehydrocorticosterone is catalyzed by a dehydrogenase utilizing either NAD or NADP while the oxidation of 19-hydroxy-DOC is catalyzed by an oxidase requiring NADPH. The 11-dehydrocorticosterone is stable in this enzyme preparation while 19-oxo-DOC is metabolized to two additional products, which are tentatively identified as 19-oic-DOC and 19 norcorticosterone. 19-nor-DOC was found to be hydroxylated at a rate that is 20% faster than the rate for DOC under the same conditions. It is therefore possible that 19-norcorticosterone can arise from 19-oic-DOC via decarboxylation to 19-nor DOC and subsequent 11-hydroxylation, but the kinetics of its formation suggest that it may actually be formed directly from 19-oxo-DOC without free intermediates. 4-Androstene-3,17-dione and 17-hydroxy-DOC were also substrates for this 11,19-hydroxylase, but 18-hydroxy-DOC was not. Maintenance of hamsters on a low sodium diet had no effect on the metabolism of DOC by the isolated adrenal mitochondria. PMID- 1606049 TI - The effect of dietary calcium supplementation on intestinal lipid metabolism. AB - Population studies in man and experimental animal work support the contention that dietary supplementation with calcium may prevent the development of colorectal cancer. The mechanism of action is postulated to be bile acid chelation in the small-bowed forming non-toxic calcium soap compounds but such substances have yet to be isolated and quantified. In this 2-part study faecal concentrations of acidic lipids and neutral sterols were measured in 93 Sprague Dawley rats whose calcium intake was modulated by enriching the chow and adding calcium lactate (24 milligrams) to the drinking water. In study-1 (dietary calcium intake doubled from 0.4-0.8%) small bowel resection was used to manipulate colonic lipid concentration for comparison with control rats who had undergone transection with immediate restoration of bowel continuity at an equivalent point. Faecal concentrations of free bile acids were 53-67% less in animals receiving added calcium [1.76 +/- 1.33 vs 0.82 +/- 0.65 mg/g (transection); 2.74 +/- 3.73 vs 1.03 +/- 1.27 mg/g (small bowel resection): P less than 0.001]. In study-2 (dietary calcium intake trebled to 1.21%) faecal bile acid concentration was reduced by 32% (1.86 +/- 0.57 vs 1.27 +/- 0.34 mg/g: NS) whereas long chain fatty acid concentrations were increased by 117% (6.77 +/- 2.39 vs 14.67 +/- 4.82 mg/g: P less than 0.001) in animals receiving added calcium. Serum calcium levels remained unchanged in these animals. Calcium soaps of the bile acids were not detected in faeces and therefore contrary to popular theory these results indicate that conditions within the intestinal lumen favour calcium chelation of long chain fatty acids rather than bile acids. PMID- 1606050 TI - Metabolism of [4-14C]estrone in hamster and rat hepatic and renal microsomes: species-, sex- and age-specific differences. AB - The metabolism of [4-14C]estrone (E1) was examined in liver and kidney microsomes of adult castrated male and ovariectomized female hamsters and rats and in neonatal and immature hamster renal microsomes. In castrated male hamster liver microsomes, E1 was metabolized extensively to six major metabolites; 15 beta hydroxyestrone, 7 alpha-hydroxyestrone, 6 alpha-hydroxyestrone, 6 beta hydroxyestrone, 2-hydroxyestrone, and delta(9,11)-dehydroestrone, and a nonpolar fraction. Six minor metabolites of E1 were also detected. In contrast, kidney microsomes derived from castrated male hamsters metabolized E1 to mainly 17 beta estradiol, 2- and 4-hydroxyestrone, 6 alpha-hydroxyestrone, 6 beta-hydroxyestrone and one monohydroxyestradiol metabolite. However, 16 alpha-hydroxyestrone was not detected. A variable, but low amount of estriol was also found. Interestingly, the quantity of 2-hydroxyestrone found in kidney microsomes of the hamster represented 26% of the total amount of metabolites formed, whereas in liver microsomes, only 9% of the overall metabolism resulted in the formation of 2 hydroxyestrone. The ability of kidney microsomes of female ovariectomized hamsters and two different rat strains to metabolize E1 was 5.9- and 9.4-fold lower, respectively, compared to renal microsomes of male castrated hamsters. The onset of oxidative metabolism in newborn hamster kidneys during development was also assessed. The results indicate that the oxidative metabolism of [14C]E1 in renal microsomes of newborn hamsters was 20-fold less than in kidney microsomes of adult hamsters. While catechol E1 metabolites were essentially negligible in hamster kidneys of these ages, it was evident that the conversion of E1 to estradiol via 17 beta-hydroxysteroid dehydrogenase resembles levels seen in the adult animals. Between the age of one and two months, the male hamster kidney exhibited the capacity to metabolize E1 at levels seen in fully mature adult hamsters. PMID- 1606051 TI - Studies on anabolic steroids--11. 18-hydroxylated metabolites of mesterolone, methenolone and stenbolone: new steroids isolated from human urine. AB - New metabolites of mesterolone, methenolone and stenbolone bearing a C18 hydroxyl group were isolated from the steroid glucuronide fraction of urine specimens collected after administration of single 50 mg doses of these steroids to human subjects. Mesterolone gave rise to four metabolites which were identified by gas chromatography/mass spectrometry as 18-hydroxy-1 alpha-methyl-5 alpha-androstan 3,17-dione 1, 3 alpha,18-dihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 2, 3 beta,18-dihydroxy-1-alpha-methyl-5 alpha-androstan-17-one 3 and 3 alpha,6 xi,18 trihydroxy-1 alpha-methyl-5 alpha-androstan-17-one 4. These data suggest that mesterolone itself was not hydroxylated at C18, but rather 1 alpha-methyl-5 alpha androstan-3,17-dione, an intermediate metabolite which results from oxidation of mesterolone 17-hydroxyl group. In addition to hydroxylation at C18, reduction of the 3-keto group and further hydroxylation at C6 were other reactions that led to the formation of these metabolites. It is of interest to note that in the case of both methenolone and stenbolone, only one 18-hydroxylated urinary metabolite namely 18-hydroxy-1-methyl-5 alpha-androst-1-ene-3,17-dione 5 and 18-hydroxy-1 methyl-5 alpha-androst-1-ene-3,17-dione 6 were both detected in post administration urine specimens. These data indicate that the presence of a methyl group at the C1 or C2 positions in the steroids studied is a structural feature that seems to favor interaction of hepatic 18-hydroxylases with these steroids. These data provide further evidence that 18-hydroxylation of endogenous steroids can also occur in extra-adrenal sites in man. PMID- 1606052 TI - The methyl-5 alpha-dihydrotestosterones mesterolone and drostanolone; gas chromatographic/mass spectrometric characterization of the urinary metabolites. AB - Before including the detection of the methyl-5 alpha-dihydrotestosterones mesterolone (1 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) and drostanolone (2 alpha-methyl-17 beta-hydroxy-5 alpha-androstan-3-one) in doping control procedures, their urinary metabolites were characterized by gas chromatography/mass spectrometry. Several metabolites were found after enzymatic hydrolysis and conversion of the respective metabolites to their trimethylsilyl enol-trimethylsilyl ether derivatives. The major metabolites of mesterolone and drostanolone were identified as 1 alpha-methyl-androsterone and 2 alpha-methyl androsterone, respectively. The parent compounds and the intermediate 3 alpha,17 beta-dihydroxysteroid metabolites were detected as well. The reduction into the corresponding 3 beta-hydroxysteroids was a minor metabolic pathway. All metabolites were found to be conjugated to glucuronic acid. PMID- 1606053 TI - Destruction of testicular cytochrome P-450 by 7 alpha-thiospironolactone is catalyzed by the 17 alpha-hydroxylase. AB - Studies were done to determine the role of the 17 alpha-hydroxylase in the conversion of 7 alpha-thiospironolactone (7 alpha-thio-SL) to a reactive metabolite causing the degradation of testicular cytochrome P-450. Incubation of guinea pig testicular microsomes with 7 alpha-thio-SL plus NADPH resulted in an approx. 70% decline in cytochrome P-450 content and even greater loss of 17 alpha hydroxylase activity. Addition of the 17 alpha-hydroxylase inhibitor, SU-10'603, to the incubation medium prevented the degradation of P-450 by 7 alpha-thio-SL. Similarly, preincubation of testicular microsomes with anti-P-45017 alpha,lyase IgG to inhibit 17 alpha-hydroxylation, diminished the subsequent loss of P-450 caused by 7 alpha-thio-SL. The results indicate that the 17 alpha-hydroxylase catalyzes the conversion of 7 alpha-thio-SL to the reactive metabolite responsible for P-450 destruction. The accompanying loss of 17 alpha-hydroxylase activity supports the hypothesis that suicide inhibition is the mechanism involved. PMID- 1606054 TI - Current epidemiological trends of HIV infection in Asia. PMID- 1606055 TI - Toxoplasmic encephalitis. PMID- 1606056 TI - Disseminated Mycobacterium avium complex infection. PMID- 1606057 TI - Pathophysiology of the AIDS wasting syndrome. PMID- 1606058 TI - Oral lesions of HIV infection: features and therapy. PMID- 1606059 TI - Predictors of HIV disease progression in the era of prophylactic therapies. PMID- 1606060 TI - AIDS-associated Kaposi's sarcoma. AB - The underlying degree of immune suppression is an important consideration in the selection of treatment for AIDS-KS. In general, subjects with CD4+ T lymphocytes greater than 500/mm3 require only local therapy unless there is some specific disability caused by the AIDS-KS lesions. Subjects with CD4+ T lymphocytes between 200 and 500/mm3 may respond to recombinant interferon. This therapy is effective in controlling AIDS-KS, can be combined with zidovudine, and has anti HIV properties. If interferon-alpha with zidovudine is clinically ineffective, systemic chemotherapy may then be required. Subjects with AIDS-KS and CD4+ T lymphocytes less than 200/mm3 should receive PCP prophylaxis, may require systemic chemotherapy, and should be maintained on antiretroviral therapy. Therapy of AIDS-KS is not curative, and a treatment plan of the underlying immune deficiency is essential for planning and implementing rational therapy. AIDS-KS is rarely life threatening but often cosmetically and functionally disabling. Treatment plans remain focused on palliative goals and include reduction of extremity or facial edema, elimination of painful lesions, relief of gastrointestinal disturbances induced by AIDS-KS lesions (including symptoms of outlet obstruction, diarrhea, and rarely blood loss), and reduction of the pulmonary burden of AIDS-KS to improve oxygenation and relieve obstructive pneumonias. PMID- 1606061 TI - Burnout among HIV/AIDS health care providers. Helping the people on the frontlines. AB - Human immunodeficiency virus disease has presented the medical professional with many challenges over the past 10 years. In the decade ahead, one aspect of working in the field that is certainly becoming an increasingly formidable issue will be dealing with AIDS-related burnout among health care professionals. The risks of AIDS-related burnout are multiple. If providers cannot find effective strategies for coping, it is possible that some of the most sensitive and compassionate workers in the field may leave to seek less stressful career opportunities. Those who focus on the negative impact that HIV disease has had on society will react with increased finger pointing to the risk of burning out as another negative consequence of working with HIV infection. Individual burnout will ultimately impact on the organization requiring interventions at that level as well. Setting up mechanisms for both individuals and organizational systems to combat AIDS-related burnout will, in the short run, add to increased costs of care in a disease already noted for its high treatment expense. However, intervening to prevent AIDS-related burnout will ultimately be cost effective by minimizing its negative effects on individuals and institutions. Learning how to cope with AIDS-related burnout may benefit the medical professional caring for patients with HIV disease as well as the profession as a whole. Facilitation of communication among individuals will certainly be fostered. Already we have seen a reorganization of delivery of health care that encourages the emphasis on integration of the patient into a true partnership with their provider. Becoming aware of the problem of AIDS-related burnout and attempting to prevent it can only serve to foster greater humanism in service professionals. A report of the National Academy of Science Committee for the oversight of AIDS activities recommended in 1988 that "research funding be made available to examine the feasibility and effectiveness of programs to alleviate stress in health care workers who care for AIDS patients." Such funding is long overdue and should be made available immediately. As we enter the second decade of facing the complex challenges of the HIV epidemic, the stress could potentially become overwhelming. Dysfunctional health care providers need not become part of the problem. Now is the time to find solutions. PMID- 1606062 TI - Management of HIV disease in women. PMID- 1606063 TI - Recognition of tumor-associated antigens by T lymphocytes: from basic concepts to new approaches. PMID- 1606064 TI - Treatment of advanced ovarian cancer: 10 years of experience. AB - Although the majority of the patients with advanced ovarian cancer will die of the disease, optimism is justified in view of the improved results of surgery followed by cisplatin--and carboplatin-based chemotherapy. Currently, approximately 30% of the patients reach a complete remission and a long therapy free period with a good quality of life after treatment with 6 cycles of cyclophosphamide and cisplatin. Cisplatin-based two-, three-, and four-drug regimens probably give equal results, with respect to survival outcome, if equitoxic dosages are used. Because of its more favourable toxicity spectrum, carboplatin is likely to replace cisplatin in the near future. The group of long term survivors includes patients with a good performance status, a well differentiated tumour, and small tumour residuals after the initial laparotomy. Patients who relapse after a period without treatment may benefit from retreatment with cisplatin or the analogue, carboplatin, given alone or in combination with cyclophosphamide. New promising approaches are now being tested in clinical trials and may be expected to yield new ways to improve treatment results. Results of fundamental research may lead to the development of new treatment strategies in the next decade and further improve the outlook for patients with ovarian cancer. PMID- 1606065 TI - Clinical cancer research: cancer treatment from the 'Red Baron' Dresden. PMID- 1606066 TI - Does extra height justify a higher risk of breast cancer? AB - While there are no firm data with respect to its oncogenic potential in the human breast, increasing evidence of the mitogenic activity of IGF on breast tissue at the time of puberty suggests caution in the use of recombinant growth hormone in the treatment of short prepubertal girls. This applies to those without evidence of classic growth hormone deficiency, particularly in the presence of a family history of breast cancer. PMID- 1606067 TI - Cyclophosphamide, adriamycin and cisplatin (CAP) versus cyclophosphamide, adriamycin and vincristin (CAV) in the treatment of advanced ovarian cancer: a randomized study. AB - Two combinations of chemotherapy agents were compared for therapeutic effectiveness on 83 patients with advanced ovarian carcinoma (stages III and IV) in a prospective single-blind randomized trial. Forty-two patients were treated with cyclophosphamide, adriamycin, and vincristin (CAV), and 41 patients were treated with cyclophosphamide, adriamycin, and cisplatin (CAP). In the CAP treated group 34 (82.9%) and in the CAV treated group 23 (54.8%) responded to cytostatic therapy. The median progression free interval was longer in the CAP (14 months) than in the CAV (10 months) treatment group. The median survival was 24 months and 15 months in favor of the CAP therapy. The log-rank and Wilcoxon statistics for the comparison of the progression free interval and survival curves indicated statistically significant therapeutic advantages for the CAP treatment combination. PMID- 1606068 TI - Chronological age is a multifactorial prognostic variable in patients with non Hodgkin's lymphoma. AB - In order to assess the predictive capacity of chronological age for survival, an analysis of prognostic variables was performed on 277 patients with Non-Hodgkin's Lymphoma, 84 of whom were older than 65 years. All patients were seen at a single institution, and elderly patients, who might otherwise have been excluded from study analysis, were included. Seventeen clinical, radiological and laboratory parameters were evaluated and subjected to univariate and multivariate analyses. Patients older than 65 years had a significantly poorer survival than those younger than 65 years. When the whole group was considered in a multivariate (Cox) model, the factors that independently predicted a longer survival were a good performance status, age less than 65 years and a low grade histological subtype. When patients older and younger than 65 years were analyzed separately the prognostic variables in the elderly were found to be similar to those in younger patients. The predictive capacity of chronological age was found to be influenced by a poor performance status, the presence of concomitant disease, the dose intensity and tolerance of the treatment given, as well as the physiological reserve of the patient. It is concluded that chronological age is a multifactorial prognostic parameter encompassing a number of patient and treatment factors, all of which must be considered when evaluating the capacity of chronological age to predict survival in patients with Non-Hodgkin's Lymphoma. PMID- 1606069 TI - Europeans still undecided on chemoprevention for breast cancer. PMID- 1606070 TI - Extramedullary plasmacytoma: clinical behaviour and response to treatment. AB - The clinical features and response to treatment of 35 patients (pts) with extramedullary plasmacytoma (EMP) were retrospectively analysed. The median age at diagnosis was 49 years (28-72). Twenty-two pts (63%) had stage I disease (localized to the primary site) 12 of whom (34%) had stage I-E (locally extended). Three pts (9%) had stage II (regional lymph nodes involved) and 10 (29%) stage III (disseminated disease). In locoregional disease (stages I, I-E, II) complete local control was achieved in 22 of 25 pts (88%), while in diffuse disease (stage III) complete remission (CR) was obtained in 5 of 10 pts (50%) (p = 0.05). In 9 of 18 pts treated with surgery, local control was achieved, and in 8 of the 9 patients with incomplete resection local control was obtained with additional radiation and/or chemotherapy. In 8 (66%) of the 12 pts treated with radiation complete local control was achieved. In 11 (58%) of 19 pts evaluable for initial chemotherapy CR was obtained. Three of these pts were treated with chemotherapy only and were alive and disease-free after a minimum follow-up of 8 years. The median time to relapse in local disease was 48 months versus 13 in disseminated disease. For pts with local disease the median survival time was 114 months and for disseminated disease 16 months (p = 0.0000). We conclude that in stage I chemotherapy is curative per se. In local stages (I, I-E and II) adjuvant chemotherapy should be considered, while in stage III only palliative therapy is feasible. PMID- 1606071 TI - Patient treatment on a compassionate basis: documentation of high adverse drug reaction rate. AB - The special exception mechanism was established by the Division of Cancer Treatment (DCT), National Cancer Institute (NCI), for the provision of anticancer drugs not yet approved by the Food and Drug Administration (FDA) to patients on a compassionate basis. Strict guidelines have been established for the distribution of drugs through this mechanism and for the reporting of adverse drug reactions (ADRs) with investigational drugs. These guidelines have been used to format the data base which is maintained on all ADRs submitted by investigators. In this paper, the incidence of ADRs with the eleven investigational drugs most frequently administered on special exception protocols was determined for a twelve month time period, January 1, 1985 through December 31, 1985. On special exception protocols, the overall incidence rate of ADRs was significantly greater than that seen on research protocols for the time period. For three drugs, Methyl G, DBD, and AMSA, the ADR incidence rate was seven to fifteen-fold greater on special exception protocols than on research protocols. In an analysis of all ADRs submitted to the FDA for the twelve months time period, no difference was found in the frequency of distribution of either types of adverse effects or the causal assessments of ADRs on special exception and research protocols. PMID- 1606072 TI - Expression of MDR1 and GST-pi in human soft tissue sarcomas: relation to drug resistance and biological aggressiveness. AB - Human soft tissue sarcomas (HSTS) in adults are a family of mesenchymal tumors characterized by high biological aggressiveness and general refractoriness to chemotherapy. A series of 36 HSTS, 24 untreated and 12 homogeneously treated with a presurgical chemotherapeutic regimen consisting of doxorubicin (intra-arterial) and iphosphamide (intra-vein), was analyzed for expression of MDR1 and the glutathione-S-transferase-pi (GST-pi) gene in order to identify molecular phenomena which may be implicated in the chemoresistance displayed by these tumors. The MDR1 gene was expressed in a greater percentage of drug-treated tumors and at higher levels than in untreated ones. By contrast, chemotherapeutic treatment has no effect on GST-pi mRNA expression. The GST-pi expression level (EL) was much higher in the HSTS with biologically aggressive features. In fact, significant correlations were observed between GST-pi and histologic grade (p = 0.01); aneuploidy (p less than 0.01); and histone H3 EL (p = 0.01), suggesting a possible causal relationship between GST-pi activity and biological aggressiveness in HSTS. PMID- 1606073 TI - Immunocytochemical determination of the estrogen-regulated proteins Mr 24,000, Mr 52,000 and DF3 breast cancer associated antigen: clinical value in advanced breast cancer and correlation with estrogen receptor. AB - The Mr 24,000 and Mr 52,000 estrogen-regulated cytosol proteins, and the breast cancer-associated antigen DF3 have been studied in an immunocytochemical assay. Primary tumor specimens from 119 patients with advanced breast cancer who received endocrine therapy have been studied. Monoclonal antibodies were used for the detection of the proteins in formalin-fixed paraffin-embedded blocks. No correlation between Mr 52,000-positive specimens and the presence of estrogen receptor (ER) could be established (p = 0.87, chi-square test) whereas a statistically significant association between Mr 24,000 (p = 0.0002), DF3 antigen (p = 0.044) and ER was demonstrated. No intercorrelation was found between Mr 24,000 and Mr 52,000 or DF3 (p = 0.63, 0.98 and 0.12 respectively). Clinical response was evaluated for immunocytochemical findings, Mr 24,000 (p = 0.37), Mr 52,000 (p = 0.61) and DF3 (p = 0.68) showed no association whereas ER was statistically correlated (p = 0.00005). Neither overall survival nor disease-free survival correlated to Mr 24,000 (p = 0.18 and 0.75 respectively, logrank test), Mr 52,000 (p = 0.095 and 0.38), or DF3 (p = 0.22 and 0.13) staining, whereas ER positive tumors did (p = 0.00005). Discrimination between ER-positive responders and ER-positive non-responders was not possible using either Mr 52,000, Mr 24,000 or DF3 staining. Based on our findings we conclude that immunocytochemical staining for Mr 52,000, Mr 24,000 or DF3 cannot be used as a marker to predict response to endocrine therapy in patients with advanced or recurrent breast cancer. PMID- 1606075 TI - Phase II study of sulofenur (LY186641) in measurable metastatic renal cancer. PMID- 1606074 TI - Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: a feasible and active approach. AB - To increase the complete remission (CR) rate achieved with two cycles of cisplatin, continuous infusion fluorouracil (5-FU) and oral leucovorin (PFL) we added two antifolate drugs, methotrexate (MTX) and the lipophilic piritrexim (PTX), to the combination (PFL-MP). Twenty-eight patients with previously untreated Stage IV squamous cell carcinoma of the head and neck received 2 cycles of cisplatin 100 mg/m2 on day 1 followed by a 5-day continuous infusion of 5-FU at 800 mg/m2/day and 100 mg of leucovorin administered orally every 4 hours. MTX was administered at 40 mg/m2 IV on day 15 and PTX at 75 mg orally twice daily on days 22 to 26, with cycle 2 starting on day 36. After 2 of the first 5 patients had tumor progression between days 15 and 35, the regimen was intensified to MTX 50 mg/m2, PTX 100 mg twice daily and a cycle duration of 28 days. Local therapy consisted of surgery and/or radiotherapy with concomitant 5-FU and hydroxyurea (FHX) administered every other week. Eleven patients (39%, 95% confidence intervals 21-57%) had a CR, 9 (32%) had a PR, and four patients had no response. Four patients were unevaluable for response to PFL-MP. Patients with poor performance status or N3 disease were less likely to achieve a CR. Mucositis following PFL was the dose-limiting toxicity. Local therapy included surgery in 15 patients and FHX chemoradiotherapy in 19 patients. The administration of FHX in this setting proved feasible and the regimen was given near the intended dose intensity in the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606076 TI - Is interferon-a an active agent in Castleman's disease? PMID- 1606077 TI - Randomized clinical trial with a weekly regimen of 5-FU vs 5-FU + intermediate dose folinic acid in the treatment of advanced colo-rectal cancer. PMID- 1606078 TI - Very high endothelin plasma levels in patients with 5-FU cardiotoxicity. PMID- 1606079 TI - When to test new drugs in chemosensitive tumors? PMID- 1606080 TI - Redressing the balance--the ethics of not entering an eligible patient on a randomised clinical trial. AB - A double standard exists whereby a treatment given outside a clinical trial is less stringently reviewed than a protocol treatment. We propose a remedy which would require the decision not to participate in an approved, available clinical trial to be subject to the same ethical requirements as trial entry. PMID- 1606081 TI - Considerable side effects of chemoembolization for colorectal carcinoma metastatic to the liver. AB - The feasibility of one whole liver chemoembolization (CE) procedure with Angiostat, a vasoocclusive collagen, mitomycin, doxorubicin, and cisplatin was evaluated in eight patients with unresectable colorectal carcinoma metastatic to the liver and good performance status. One heavily pretreated patient showed a partial response in the liver lasting 188 days. Five patients had stabilization of the disease for 85-150 days. The side effects of the treatment were considerable with a fatigue syndrome lasting up to eight weeks, chemical and ischemic hepatitis, severe thrombopenia (WHO grade 4 in 2 pts) and icterus being the most disturbing toxicities. We recommend to restrict CE to patients with a life expectancy of more than 4-6 months confined to protocols, which evaluate efficacy, toxicity and influence on quality of life of CE with various cytotoxic drugs. We further suggest to perform staged unilobar CE at 4- to 6-week intervals rather than whole liver CE. PMID- 1606082 TI - Salvage radiotherapy in recurrent Hodgkin's disease. AB - Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year. PMID- 1606083 TI - Stage I malignant lymphoma of Waldeyer's ring: frequent relapse after radiation therapy. AB - The natural history and therapeutic results of 26 patients with stage I malignant lymphoma of Waldeyer's ring (ML-WR) were analyzed retrospectively. Complete response was achieved in all 26. Relapse occurred in 9 of 21 (43%) patients treated with radiation therapy (RT) alone, while no relapse was seen in those treated with a combination chemotherapy consisting of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP therapy). Relapse occurred within 1 year in 8 of the 9 patients. Relapse-free survival in the patients treated with RT alone was considered suboptimal. PMID- 1606084 TI - A phase I trial of a new antiemetic drug--clebopride malate--in cisplatin-treated patients. AB - Clebopride, a new benzamide derivative, has, in common with the other members of this group, antidopaminergic activity. In animals, its therapeutic ratio is superior to that of metoclopramide at doses free of side effects associated with hyperprolactinemia and extrapyramidal symptoms. The present study was designed to define the maximum tolerated dose (MTD) in patients with advanced histologically proven cancer, treated with cisplatin at a dose of greater than 50 mg/m2. Most of them were pretreated and refractory to standard antiemetics. Clebopride was started at a dosage of 0.10 mg/kg in a group of 6 patients and escalated by 0.2 mg at each dose level. A total of 30 patients were included. Side effects include somnolence, diarrhea and extrapyramidal-like symptoms. The latter occurred at almost all dose levels in 14% of the cycles and limited continuation of the study. Activity in this group of patients was encouraging but, considering the rate of extrapyramidal symptoms, further dose escalation is not indicated and activity at lower, nontoxic levels should be investigated. PMID- 1606085 TI - Pretransplant conditioning with busulfan and cyclophosphamide in acute leukemia patients: neurological and electroencephalographic prospective study. AB - A neurological and electroencephalographic (EEG) prospective study was performed in 34 leukemic patients receiving busulfan (BU) plus cyclophosphamide (CY) before bone marrow autologous transplant. During BU treatment and briefly thereafter, all patients were given anticonvulsant prophylaxis with phenobarbital. Neurological evaluations were performed daily and EEGs, recorded one week before and soon after the end of the BU regimen, were re-evaluated two months later. Basal EEGs were normal in 23 of the 34 patients, focal abnormalities were detected in 9 cases, and generalized epileptic discharges were present in one (one subject was not studied). EEGs performed at the end of BU administration showed generalized spike/polyspike-and-wave discharges in 21 of the 34 patients, with associated myoclonic epilepsy in 10 subjects appearing on the 3rd or 4th day of treatment. Focal abnormalities were present in 6 patients and constant EEG normality in 7. It is known that myoclonic epilepsy can be induced by drugs. Oral administration of high-dose BU is followed by a high-dose cerebrospinal fluid concentration of the drug. Therefore, myoclonic epilepsy and/or paroxysmal epileptiform EEG discharges may be observed in leukemic patients undergoing high dose BU therapy. PMID- 1606086 TI - Intraperitoneal therapy for ovarian cancer: analysis of fluid distribution by computerized tomography. AB - Nineteen patients with ovarian cancer and minimal residual or persistent disease who were treated with cisplatin or carboplatin-based intraperitoneal (IP) regimens had distribution studies of IP contrast and computerized tomography prior to and during treatment. The distribution pattern was assessed retrospectively and scored for the presence of contrast in each of eight regions: the under surface of right and left diaphragms, the right and left paracolic gutters, the lesser omental sac, the intramesenteric region and the true and false pelvis. Assigning a point to each region with adequate distribution, we classified 10 patients to an excellent pattern (greater than or equal to 7 of 8 regions), 6 to a good pattern (5 to less than 7 regions), and 3 to an inadequate distribution pattern (less than 5 regions). Serial studies were performed in 8 patients after more than 4 cycles of IP therapy. In these patients, all of whom were tolerating treatment without progression, the distribution remained virtually unchanged for those with excellent distribution. One of three with good distribution manifested inadequate distribution on repeat study, and one of two with inadequate distribution improved to show a good pattern. In this small study there was no correlation of distribution patterns with plasma CA-125 at onset of IP treatment and prior surgical procedures or placement of the catheter tip. However, three patients with unsatisfactory patterns had procedures consisting of catheter placement only rather than formal reassessment laparotomies for ovarian cancer. Since satisfactory IP distribution may be required for obtaining a therapeutic advantage from IP therapy, methods for its assessment must be developed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606087 TI - Increased susceptibility to lymphokine activated killer (LAK) lysis of relapsing vs. newly diagnosed acute leukemic cells without changes in drug resistance or in the expression of adhesion molecules. AB - The NK and LAK activity of peripheral blood lymphocytes of leukemic patients as well as the susceptibility of their acute myeloid (AML) and lymphoblastic (ALL) leukemia cells to autologous and allogeneic LAKs were examined. In addition, neoplastic cells at diagnosis and at relapse were compared in the same patients for several features, including in vitro susceptibility to LAKs and to the drugs used in the induction phase, expression of MDR phenotype and of adhesion molecules, and differentiation markers. The NK activity of patients' LAK cells on K562 was significantly lower than that of a group of healthy donors whereas no differences were found in LAK activity as evaluated on Daudi cells. Three of 5 AML and 3 of 4 ALL were significantly more susceptible to autologous and allogeneic LAK lysis when blasts obtained at relapse were compared with leukemic cells of the same patients at diagnosis. This different lysability was not associated with in vitro modified sensitivity to drugs used in induction treatment. Moreover, no elevation in the expression of the multidrug-resistance (MDR)-related P170 glycoprotein was noted in relapsing leukemic cells. Even the expression of adhesion molecules and differentiation markers did not correlate with lysability of leukemic cells. These data demonstrate that relapsing leukemic blasts can be significantly lysed by LAK cells and suggest a rationale for adoptive immunotherapy with IL-2 and LAK cells in the treatment of acute leukemic patients. PMID- 1606088 TI - Mitoxantrone and mitomycin C as second-line treatment for advanced breast cancer. AB - Forty-three evaluable patients with advanced breast cancer were treated with a combination of mitoxantrone 10 mg/sqm and mitomycin C 10 mg/sqm every 3 weeks. Two patients (4%) achieved objective responses lasting 3 and 16 months. The median duration of survival after protocol entry was 6 months (range 1-22) and the median progression-free survival was 3.5 (range 1-20). Only mild toxicities were observed. We concluded that the mitoxantrone and mitomycin C combination has limited toxicity but low activity and only brief disease palliation in advanced breast cancer. PMID- 1606089 TI - A phase II study of high dose tamoxifen in progressive, metastatic renal cell carcinoma. AB - Thirty-four patients with progressive advanced renal cell carcinoma (RCC) were treated with high-dose tamoxifen (HD-TAM) 100 mg/m2 p.o. daily until progression. The overall remission rate was 12%, including 1 complete remission. Seventeen of the thirty-four (50%) patients had minor remission or no change. Taking into consideration the documented progression prior to tamoxifen therapy, further tumour growth could be arrested in 62% (1 CR, 3 PR, 17 MR/NC) of the patients. Median response duration for CR/PR was 20 months (range 6-21+) and median progression-free survival for MR/NC was 6 months (range 2-15). The one-year survival rate was 41%. Patients with only pulmonary metastases, good performance status and prior nephrectomy seemed to have a better survival. Side effects were comparable to those of conventional doses of tamoxifen (20-30 mg p.o. daily). These data suggest that HD-TAM may be a useful therapeutic approach with low toxicity, considering that, in metastatic RCC, the treatment intent is at best palliative. PMID- 1606090 TI - The prognostic role of metastatic pattern in colorectal adenocarcinoma. PMID- 1606091 TI - Severe autoimmune hemolytic anemia in two patients treated with fludarabine for chronic lymphocytic leukemia. PMID- 1606092 TI - Serum erythropoietin levels in patients with Hodgkin's lymphoma at the time of diagnosis. PMID- 1606093 TI - Lessons from 1100 pediatric caudal blocks in a teaching hospital. AB - METHODS: The demographic and technical data of all the pediatric caudal blocks (CBs) performed from August 1986 to September 1989 in our teaching hospital were prospectively collected on a computerized protocol. Except for 22 high-risk ex premature infants, all CBs were performed under halothane or isoflurane anesthesia, after premedication with atropine. Moreover, they were performed using local anesthetic solutions containing 1:200,000 epinephrine. A total of 1100 CBs were performed in children younger than 7 years; 203 patients weighed 5 kg or less; 260, 5.1-10 kg; 300, 10.1-15 kg; and 337, more than 15.1 kg. The CBs were also analyzed according to the anesthesiologist's experience with CB: 184 were performed by anesthesiologists who had performed fewer than 10 CBs (Group A); 210, 10-20 CBs (Group B), and 704, more than 20 CBs (Group C). RESULTS: We found difficult landmarks in 11.2% of our patients. Moreover, it was significantly more frequent (p = 0.0004) if the patients weighed less than 10 kg, because of poor anatomy or obesity. There were 76 bloody taps (BTs, 6.9%); although there was a statistically insignificant trend toward a lower incidence of BTs in the 5.1-10-kg group, experience seemed to influence the incidence of BTs, as it decreased from 11.4% in Group A to 8.9% and 5.4% in Groups B and C, respectively (p less than 0.05). There were eight systemic reactions (i.e., brisk onset of tachycardia during or shortly after the CB), which were all short-lived and responded quickly to hyperventilation with oxygen. Two occurred despite repositioning the needle after a previous BT, but six occurred with no previous evidence of blood and were thus called "concealed" BTs. Moreover, all occurred in children weighing 10 kg or less. There was only one dural tap. Only nine CBs (0.81%) failed to provide effective intraoperative anesthesia, and 93% of the patients left the recovery room without having required narcotic or non-narcotic analgesics. CONCLUSIONS: Our results confirm that CB is a reliable technique, easy to perform by beginners. It should be stressed, however, that small infants are at increased risk of concealed BTs. PMID- 1606094 TI - The antiemetic efficacy and safety of prophylactic metoclopramide for elective cesarean delivery during spinal anesthesia. AB - BACKGROUND AND OBJECTIVES: The efficacy and safety of intravenous metoclopramide administered prophylactically before elective cesarean delivery under spinal anesthesia was studied. METHODS: In a double-blind, randomized fashion, 42 ASA Physical Status I-II parturients at term were assigned to receive either 10-mg intravenous metoclopramide or an equal volume of normal saline before induction of spinal anesthesia. The occurrence of nausea and/or vomiting recorded throughout the perioperative period until the patient was admitted to the recovery room. Neonatal acid-base status and neurobehavioral exams were obtained. RESULTS: Patients in the group receiving metoclopramide had a significantly lower incidence of nausea and vomiting both before and after delivery than the control group (14% versus 81% overall). All neonatal acid-base values were within normal limits and there were no significant differences in neurobehavioral exam results between the two groups. CONCLUSIONS: Metoclopramide administered before induction of spinal anesthesia for cesarean delivery appears to significantly reduce both pre- and postdelivery emetic symptoms without apparent adverse effects on mother or neonate. PMID- 1606095 TI - Benzodiazepine premedication causes hypoxemia during spinal anesthesia in geriatric patients. AB - BACKGROUND AND OBJECTIVES: The use of sedatives during regional anesthesia can lead to life-threatening hypoxemia. Older patients particularly are prone to enhanced effects of these drugs. We studies whether oral premedication with benzodiazepines produced hypoxemia during spinal anesthesia in elderly patients. METHODS: In a prospective, double-blind, and randomized study, we evaluated the effect of oral benzodiazepine premedication on the incidence of hypoxemia measured by pulse oximetry (arterial oxygen saturation less than 90% for 30 seconds or longer) during surgery under spinal anesthesia in 80 geriatric patients divided into four equal groups: 1, control, no premedication; 2, 1 mg flunitrazepam; 3, 1 mg lorazepam; and 4, 7.5 mg midazolam. RESULTS: The incidence of hypoxemia in the four groups was: 1, 15%; 2, 45%; 3, 20%; and 4, 60% (p = 0.0078); overall incidence was 42% in premedicated patients versus 15% in unpremedicated controls (p = 0.0304). Seventy-four percent of patients who presented drowsiness and anesthetic level above T7 had desaturation compared to only 7% of those who were awake and had lower level (p less than 0.0005). No association between hypoxemia and other factors (age, weight, ASA physical status, and position during surgery) was found. All the episodes of desaturation were easily corrected with low supplemental oxygen concentrations. CONCLUSIONS: Premedication with oral benzodiazepines may produce hypoxemia during spinal anesthesia in elderly patients. Lorazepam appeared safer than flunitrazepam and midazolam. Monitoring of arterial blood oxygen saturation and/or supplemental oxygen is mandatory in geriatric patients with high spinal anesthetic level and/or drowsiness during surgery. PMID- 1606096 TI - Effect of epidural analgesia on colorectal anastomotic healing and colonic motility. AB - BACKGROUND AND OBJECTIVES: To examine the effect of epidural local anesthetic and narcotic agents on colonic anastomotic healing. METHODS: A prospective randomized study was conducted in a porcine model. Twenty-one pigs undergoing colorectal resection and anastomosis were randomized to receive either bupivacaine (Group 1), morphine (Group 2), or normal saline (Group 3) by intraoperative and postoperative epidural infusion. Colonic blood flow was measured using laser doppler velocimetry and colonic motility assessed with radio-opaque markers and daily x-rays postoperatively. Seven days postoperatively, the anastomoses were resected and analysis of bursting pressure and hydroxyproline content performed. RESULTS: In this porcine model, epidural anesthesia accelerated colonic transit time. Group 1 and 2 animals had significantly faster colonic transit time (3.9 and 4 days, respectively) when compared with Group 3 animals (6 days; p less than 0.05, chi-square analysis). There was no statistically significant difference in blood flow, bursting pressure, and hydroxyproline content between the three groups, and no anastomotic complications occurred in any animal. CONCLUSIONS: These findings suggest in this model that postoperative epidural analgesia is a safe technique after colorectal resection and anastomosis. PMID- 1606097 TI - Adding clonidine to mepivacaine prolongs the duration of anesthesia and analgesia after axillary brachial plexus block. AB - BACKGROUND AND OBJECTIVES: This study evaluates the effects of clonidine added to mepivacaine on the duration of anesthesia and analgesia after axillary brachial plexus block. METHODS: Thirty patients scheduled for elective hand surgery were divided into three equal groups in a randomized, double-blinded fashion. An axillary perivascular brachial plexus block was performed with 40 ml 1% mepivacaine plus 1:200,000 epinephrine in the three groups. Group B also received 150 micrograms clonidine subcutaneously and Group C had the same dose of clonidine mixed with the local anesthetic and injected into the plexus sheath. The following variables were recorded: onset time, duration of anesthesia, duration of analgesia, postoperative pain score, intake of analgesics, and adverse effects. RESULTS: The three groups were comparable in terms of age, sex, weight, height, onset time of anesthesia, postoperative pain score, and analgesic requirement. The duration of anesthesia and analgesia was comparable in Groups A and B, but both variables were significantly increased in Group C: the duration of anesthesia and analgesia were prolonged, respectively, by 37 +/- 6% and 103 +/ 16% when compared to Group A and by 32 +/- 7% and 89 +/- 15% when compared to Group B. No side effects were reported. CONCLUSIONS: One hundred fifty micrograms clonidine added to mepivacaine for brachial plexus block prolongs the duration of anesthesia and analgesia. Our results suggest that this effect of clonidine is local rather than systemic. PMID- 1606098 TI - The NerveSeeker: a system for automated nerve localization. AB - BACKGROUND AND OBJECTIVES: The NerveSeeker is a new instrument for locating peripheral nerves. Like existing nerve stimulators, it is based on injecting current through the needle used for drug injection. However, the NerveSeeker was designed to automatically adjust the amplitude of the stimulating current pulses. It does this by feedback control to hold the level of response constant at a small but reliably detectable fraction of a maximal neural response. We report experimental tests of the NerveSeeker using an excised frog nerve in a transparent chamber, where we could observe the needle approach. METHODS: A control voltage proportional to the stimulus magnitude was used to indicate the proximity of the needle tip to the nerve. The proximity was validated by direct measurement of the distance from the tip of the needle to the nerve. Parameters governing the performance of the NerveSeeker in tracking needle movement were analyzed. RESULTS: The following combined strategy was found effective: As the needle approached the nerve, the stimulus was reduced in proportion to the amplitude of the recorded response; as the needle moved away, the stimulus magnitude was incremented by a constant amount (enough to increase the neural response by approximately 1% of its maximum amplitude) after each stimulus that failed to elicit a neural response exceeding the criterion value. Stimulation throughout simulated penetrations was at a frequency of 10 Hz or higher to give more immediate guidance during insertion. Optimal settings for each control parameter were determined, reflecting both engineering and physiologic tradeoffs. With these settings, the device proved successful in localizing nerves, closely tracking needle movements at velocities as high as 2 mm/second. CONCLUSION: These experimental results suggest that clinical tests of the NerveSeeker would be appropriate. PMID- 1606099 TI - A dual-chambered syringe that allows identification of the epidural space using the loss of resistance technique with air and with saline. AB - BACKGROUND AND OBJECTIVES: Each of the two most widely used techniques for identification of the epidural space, the loss of resistance technique with air and the loss of resistance technique with liquid, has certain advantages and disadvantages. A new syringe is described that has two chambers, one to contain air and the other to contain liquid, to combine the advantages of air with the advantages of liquid, and to prevent the disadvantages of each. METHODS: Twenty consecutive adult patients scheduled to receive epidural injections for surgery, obstetrics, or pain control were selected for study. This was an open study, and the EpIdent syringe was used as the only means of identifying the epidural space in every case. RESULTS: The EpIdent syringe easily and effectively identified the epidural space in all of the patients, with no adverse or unpleasant side effects. Successful identification of the space was documented by the production of adequate anesthesia after the injection of an appropriate volume or local anesthetic. There were no complications. CONCLUSIONS: The successful use of the EpIdent syringe in this preliminary study of 20 patients indicates that it provides a simple, safe, and effective means of identifying the epidural space. It allows the use of a plastic syringe (instead of glass) and avoids the unpleasant or untoward effects associated with currently used loss of resistance techniques. PMID- 1606100 TI - Pleural phenol therapy for the treatment of chronic esophageal cancer pain. AB - BACKGROUND AND OBJECTIVES: Pleural phenol was used successfully to alleviate terminal pain associated with metastatic esophageal cancer in a 43-year-old man. METHODS: The patient first was given 20 ml 0.5% bupivacaine for diagnostic purposes through an interpleural catheter to control a severe aching pain throughout the T5-8 dermatomes. Seven days later, 10 ml 6% phenol suspended in 0.5% bupivacaine was injected and produced analgesia for two days. A second injection using 18 ml 10% phenol provided adequate analgesia for the next four weeks until the patient's death. Two weeks after the lower thoracic pain was relieved, the patient had complained of a new right-sided pain in the region of C7-T2, which was treated successfully with 10 ml 10% phenol. RESULTS: During the course of this therapy, his sustained-release morphine consumption diminished from 540 mg to 90 mg despite his terminal disease. Post mortem examination and histologic studies revealed no macroscopic or microscopic changes to the viscera, spinal cord, or sympathetic chain. CONCLUSIONS: Repeated doses of phenol suspended in bupivacaine provide adequate analgesia for terminal cancer pain when administered interpleurally. No pathologic changes were detected despite a total of 3400 mg phenol delivered into the right thoracic cavity. PMID- 1606101 TI - Epidural fentanyl-bupivacaine infusion for management of pain in the Guillain Barre syndrome. AB - BACKGROUND AND OBJECTIVES: Epidural morphine with fentanyl has been used with some success to treat the pain associated with Guillain-Barre syndrome. This report describes a female with Guillain-Barre syndrome in which lower extremity and generalized positional pain failed to respond to conventional pain therapy. An epidural infusion of bupivacaine and fentanyl was used to treat her pain. METHODS: A case report. RESULTS: An epidural infusion of 15 mg/hour bupivacaine and 75 micrograms/hour fentanyl produced good pain relief (visual analog scale decreased from 9 to 2) and allowed increased mobility. Over 24 days of treatment, the infusion requirements gradually increased, suggestive of tachyphylaxis. CONCLUSIONS: These patients sometimes fail to respond to conventional pain therapy and may require the expertise of an anesthesiologist to deliver epidural analgesics. PMID- 1606102 TI - 3-in-1 blocks and continuous 3-in-1 blocks. PMID- 1606103 TI - The "3-in-1 block": is it really 4-in-1 or 2-in-1? PMID- 1606104 TI - Inappropriate use of linear regression analysis. PMID- 1606105 TI - Parallel in all planes? PMID- 1606106 TI - The coracobrachialis muscle: a guide to the axillary artery. PMID- 1606108 TI - The scourge of catheter kinking. PMID- 1606107 TI - Advantage attributable to barbotage. PMID- 1606109 TI - Audit in gynaecology. PMID- 1606110 TI - Aetiology of cerebral palsy. PMID- 1606111 TI - Therapeutic uses of transcervical catheterization of the fallopian tubes. PMID- 1606112 TI - Role of the senior house officer in the labour ward. PMID- 1606113 TI - Objective measurement of anxiety in hypertensive pregnant women managed in hospital and in the community. AB - OBJECTIVES: To determine whether pregnant hypertensives women are more anxious when monitored in hospital or at homes. DESIGN: Prospective randomized controlled trial. SETTING: Rosie Maternity Hospital and women's homes. SUBJECTS: Ninety-nine pregnant hypertensive women: 50 had their blood pressure measured telemetrically from home, and 49 had it measured in hospital. MAIN OUTCOME MEASURES: Number of episodes of monitoring, duration of monitoring, mean blood pressure during monitoring, gestational age at delivery, trait and state anxiety levels. RESULTS: There were no significant differences in anxiety levels, or in any other outcome measure, between the home and hospital groups. CONCLUSION: When blood pressure is being monitored serially in pregnant hypertensive women, there is no measurable difference in their anxiety levels, whether they are in hospital or at home. PMID- 1606114 TI - The accuracy of catheter-tip pressure transducers for the measurement of intrauterine pressure in labour. AB - OBJECTIVE: To assess the reliability of intrauterine pressure measurements in labour with transducer tipped catheters. DESIGN: Prospective clinical study. SETTING: Delivery ward, National University Hospital, Singapore. SUBJECTS: 20 women admitted in early labour were randomly allocated to two groups. INTERVENTIONS: Women in the first group had two catheters that had been tied together introduced transcervically into the same amniotic fluid pocket. The second group had two catheters introduced in different directions so that each catheter tip was in a different pocket of amniotic fluid. MAIN OUTCOME MEASURE: The contraction to contraction pressure difference recorded by the two catheters in the same uterus. In addition, the cumulative uterine active pressure generated by one catheter was compared with that of the other. RESULTS: There were differences in peak pressure of up to 4-5.3 kPa (30-40 mmHg) during some contractions. The difference in pressure recordings between the two catheters could not be explained by effects of loculation of amniotic fluid. However, the pressures recorded were not systematically higher in one catheter than in the other. Cumulative uterine activity was very similar when assessed by each catheter in the same uterus. CONCLUSION: Intrauterine pressure measurements using transducer tipped catheters provide reliable information on the cumulative pressure wherever the catheter tip was sited in the uterus, but there are variations in pressures recorded during individual contractions. PMID- 1606115 TI - Prenatal microbiological risk factors associated with preterm birth. AB - OBJECTIVE: To study the vaginal flora of pregnant women at 22-28 weeks gestation to determine whether the presence of specific micro-organisms is significantly associated with preterm birth and prelabour rupture of the membranes. DESIGN: A comprehensive descriptive prospective study of the vaginal micro-flora of women between 22-28 weeks gestation comparing those who gave birth preterm (less than 37 weeks) with those who gave birth at term. Microbiological assessment included cultures for aerobic and anaerobic bacteria, yeasts, genital mycoplasmas and Trichomonas vaginalis. Multiple logistic regression analysis was used to account for confounding obstetric and demographic variables. SETTING: The Queen Victoria Hospital, Adelaide, South Australia. SUBJECTS: 135 women who gave birth preterm compared to 651 women who gave birth at term. MAIN OUTCOME MEASURE: Preterm birth and preterm prelabour rupture of membranes (PROM) RESULTS: The prevalence of Gardnerella vaginalis between 22-28 weeks was significantly higher in women who gave birth preterm compared to women who gave birth at term (23% vs 15%; multiple logistic regression odds ratio (OR) 1.8, 95% confidence intervals (CI) 1.01-3.2, P less than 0.05. Ureaplasma urealyticum was also found in a higher proportion of women who gave birth preterm (49% vs 32% OR 1.7, 95% CI 1.1-2.6, P less than 0.0005). Preterm PROM occurred in 42% of whom 60% were carriers of U. urealyticum between 22-28 weeks, compared with 32% in the term group (OR 3.2, CI 1.7-6.1, P less than 0.0005). When women who received antibiotics between the midtrimester swab and labour were excluded, G. vaginalis was also significantly associated with preterm PROM (OR 2.7, CI 1.1-6.5, P less than 0.05). The presence of vaginal enteropharyngeal bacteria (E. coli, Klebsiella spp., Haemophilus spp., Staph. aureus) in the midtrimester was not predictive of preterm birth, but when these organisms were found in labour, they appeared to have been acquired later in the pregnancy. CONCLUSION: Women carrying G. vaginalis or U. urealyticum during the midtrimester had nearly twice the risk of preterm birth, while women positive for U. urealyticum had more than a threefold risk of preterm PROM. PMID- 1606116 TI - Can out-of-hours work by junior doctors in obstetrics be reduced? AB - OBJECTIVE: Against a background of concerns about the hours of work of junior doctors, this study examines how the night-time work of junior staff in obstetrics may be reduced by giving greater responsibility to midwives. DESIGN: In the first phase of the study, the tasks undertaken at night in four hospitals were identified. In the second phase a nominal group technique was used to seek the extent of agreement among professionals about the appropriateness of postponing surgery to the following day in certain circumstances. RESULTS: There were considerable variations between hospitals in the rate of obstetric intervention and the division of tasks between doctors and midwives. The panel concluded that many tasks currently performed by senior house officers could be undertaken by midwives. CONCLUSION: This study suggests that there scope for reducing the workload of junior obstetricians at night through the adoption of an extended role by midwives. PMID- 1606117 TI - Determinants of caesarean section rates in Italy. AB - OBJECTIVE: To analyse the determinants of caesarean section rates in Italy. DESIGN: Analysis of information using a standard form on all the deliveries after the 28th week of gestation routinely collected by the Italian Central Institute of Statistics. SETTING: National data of all Italian deliveries in the periods 1980-1983. SUBJECTS: A total of more than 2,400,000 deliveries occurred in Italy in the period and are considered in this analysis. RESULTS: The frequency of caesarean section rose from 11.2/100 deliveries in 1980 to 14.5/100 in 1983. Caesarean section rates were lower in the Southern (less rich) areas, and rose steadily with maternal age, being about three times higher in women aged greater than or equal to 40 years than in teenagers. Maternal education was directly associated with caesarean section rates: compared with women with only primary school education, those with a college education reported an about 40% higher rate of caesarean section, but this difference dropped markedly after allowance for maternal age and birthweight. The section rate was 13.3/100 deliveries in public hospitals and 11.8/100 in private ones, but this reflected the different utilization of public and private services in various geographical areas. Birthweight and gestational age at delivery were important determinants of caesarean section rates; lowest values were observed for very-low-birthweight and very preterm deliveries and babies weighing 3000-3999 g and term deliveries. Caesarean section rates were about 20% higher in nulliparous than in parous women and the rates increased with number of stillbirths or miscarriages; further, the rate ratio was about double in multiple than in single births. CONCLUSION: Caesarean section rates in Italy in the early 1980s were still lower than in North America, but their determinants share several similarities with those reported in other areas. PMID- 1606118 TI - Serum and intracellular magnesium during normal pregnancy and in patients with pre-eclampsia. AB - OBJECTIVE: To determine the serum and lymphocyte magnesium concentrations during normal pregnancy and to compare the magnesium status in the third trimester of pregnancy between women with normal pregnancy and those with gestational hypertension (GH) or pre-eclampsia (PE). DESIGN: A prospective cross-sectional study followed by a prospective comparative study. SETTING: Department of Obstetrics and Gynecology, Department of Pediatrics and Genetics, Hopital Cantonal Universitaire Geneve, Switzerland. SUBJECTS: Seventy-one healthy pregnant women, with normal pregnancies between 6 and 38 weeks gestation. The second part included 43 women in the third trimester of pregnancy, 11 had GH, 11 had PE and 21 formed the comparison group of healthy normotensive women. MAIN OUTCOME MEASURES: Total serum and intralymphocytic Mg concentrations and urinary Mg excretion. RESULTS: There was a progressive reduction in total serum magnesium concentrations during normal pregnancy, thought to be partly due to haemodilution, because the decline in concentration of serum proteins paralleled that of Mg (P less than 0.001). In the three groups studied in the third trimester the serum Mg concentration was very similar in the GH and the comparison groups, but it was significantly higher in the PE group (P less than 0.01). The intralymphocytic Mg concentrations and the urinary Mg excretion were similar in all three groups. In five patients treated with MgSO4 there was a large increase in the serum Mg concentration and in the urinary Mg excretion. The intralymphocytic Mg concentration remained remarkably stable. CONCLUSIONS: Our data does not support the conclusion that Mg deficiency is the primary cause of pre-eclampsia. PMID- 1606119 TI - The effects of fetal exposure to danazol. AB - OBJECTIVE: To assess the consequences of exposure to danazol in utero. Additionally, by assessing the risk, to facilitate the counselling of pregnant women inadvertently exposed to danazol in early pregnancy. DESIGN: Retrospective review of reported case histories. SUBJECTS: 129 women exposed to danazol during pregnancy were identified from individual case reports, data from the Australian Drug Reactions Advisory Committee and the United States Food and Drug Administration and from the reports of danazol exposure made directly to the manufacturers. MAIN OUTCOME MEASURES: Teratogenic effects of fetal exposure to danazol in relation to dosage and duration of exposure. RESULTS: Of the 129 reported pregnancies, 12 miscarried and 23 were aborted. Of the 94 completed pregnancies, 37 resulted in the birth of normal males, 34 in non-virilized females and 23 in virilized females. Virilization occurred in a proportion of female fetuses with a pattern of cliteromegaly, fused labia and urogenital sinus formation. Surgery to the genital tract was usually, but not always, required in childhood. The abnormality has not been reported where danazol therapy had been discontinued before the 8th week of pregnancy. Although more common in the higher dosages, virilization was reported in one case with a 200 mg daily dosage. CONCLUSIONS: Danazol should remain contraindicated in pregnancy and clinicians should give careful contraceptive advice to patients commencing or continuing danazol therapy. Nonetheless it is possible to be cautiously optimistic about the outcome of danazol-exposed pregnancies, particularly if treatment is discontinued before 8 completed weeks gestation. PMID- 1606120 TI - A tale of two prior probabilities--avoiding the false positive antenatal diagnosis of autosomal recessive polycystic kidney disease. AB - We describe a case in which the typical ultrasound diagnosis of infantile polycystic kidney in a woman with no family history of renal disease was not confirmed by histology following termination of the pregnancy. This is contrasted with the situation in another couple who were known carriers of autosomal recessive polycystic kidney disease and where the prenatal ultrasound diagnosis was confirmed histologically. When prior genetic risk is low, the possibility of a normal or less severe outcome must be discussed with parents when fetal ultrasound shows large, echogenic kidneys but normal amniotic fluid volume. PMID- 1606121 TI - Screening for congenital heart disease prenatally. Results of a 2 1/2-year study in the South East Thames Region. AB - OBJECTIVE: To assess the efficacy of four chamber view examination, during routine obstetric scanning, in the prenatal detection of fetuses with congenital heart disease. DESIGN: Prospective observational study. SETTING: Ten obstetric ultrasound units in the South East Thames Region. SUBJECTS: All pregnant women attending for routine obstetric ultrasound examination. INTERVENTION: Ultrasonographers performing routine ultrasound examinations were taught to obtain, and correctly interpret, the four chamber view of the fetal heart. When this view could not be achieved adequately, an attempt was made to identify a reason for failure and, if possible, to arrange a repeat scan. All suspected abnormalities were referred to a specialized unit. MAIN OUTCOME MEASURES: Numbers of true abnormalities detected or overlooked, and the number in whom abnormality was suspected incorrectly. RESULTS: Over a 2.5-year period, 69% of the known number of cardiac lesions associated with an abnormality of the four chamber view were detected prenatally during the routine obstetric scan, 10% were identified as a result of referal for other high-risk factors and 21% were overlooked. The overall positive predictive value in the 10 obstetric units was 36%. CONCLUSIONS: Prenatal screening for some forms of major congenital heart disease is possible by including examination of the four chamber view of the fetal heart in routine obstetric scans. However, there are important limiting factors that will influence the success of abnormality detection and must be taken into account if screening is to be effective nationwide. PMID- 1606122 TI - The multidisciplinary management of a family with epithelial ovarian cancer. AB - OBJECTIVE: To describe the management of a family with an inherited predisposition to ovarian and breast cancer. Particular attention is paid to the problems of contraception, screening, prophylactic surgery and hormone replacement therapy. SETTING: The multidisciplinary Grampian Familial Epithelial Ovarian Cancer Study Group. SUBJECTS: 162 members of a family extending over five generations. In the third generation, five of the 10 women died with epithelial ovarian cancer. Three women in generation IV have developed pre-menopausal breast cancer. There are now 78 family members in the fifth generation aged between 2 and 22 years. INTERVENTIONS: Counselling of female family members is started at the age of 18 years. The combined oral contraceptive pill is advocated to suppress ovulation. Gynaecological follow-up after the age of 28 includes yearly pelvic examination, transvaginal ultrasonography and serum CA125 estimation. Laparoscopy with peritoneal cytology is indicated if any part of this yearly assessment is abnormal. Prophylactic oophorectomy is advised between the ages of 35 and 40 years after the family is complete. In generation IV, 20 of the 29 women have undergone prophylactic oophorectomy. Oestrogen hormone replacement therapy with a cyclical progestogen is recommended after prophylactic oophorectomy. Breast cancer screening starts at the age of 25 and involves annual clinical breast examination augmented by mammography and breast ultrasound. CONCLUSIONS: Only by the careful questioning and recording of family history, including at least third degree relatives (cousins), will similar groups with familial ovarian/breast cancer be identified. When predisposing genes are characterized it will be possible to identify carriers within the family and concentrate clinical effort on them while offering appropriate reassurance to those with decreased risk. PMID- 1606124 TI - Multiple fetal anomalies in the first trimester; detection using transvaginal ultrasound and therapeutic abortion using mifepristone (RU486) in conjunction with gemeprost vaginal pessaries. PMID- 1606123 TI - Increased whole blood platelet aggregation in normal pregnancy can be prevented in vitro by aspirin and dazmegrel (UK38485). AB - OBJECTIVE: To determine the effect of normal pregnancy and the early puerperium on whole blood platelet aggregation and to assess the role of thromboxane A2 (TXA2) in platelet aggregation in pregnancy. DESIGN: A prospective descriptive study. SETTING: TCD Medical School, St James's Hospital, Dublin. SUBJECTS: Twenty healthy primigravidae who remained normotensive during pregnancy and the puerperium. INTERVENTIONS: 20 ml blood samples were obtained serially at 12, 20, 28, 32 and 36 weeks gestation, during established labour and at 1 h, 24 h, 48 h and 6 weeks after delivery. MAIN OUTCOME MEASURES: Whole blood platelet aggregation in response to aggregating agents ADP, PAF (platelet aggregating factor) collagen, adrenaline and arachidonic acid (AA) at each stage of pregnancy and peuerperium was measured using a particle counting technique. The in vitro effect of aspirin and dazmegrel (thromboxane synthetase inhibitor UK38485) on platelet aggregation in pregnancy was also investigated. RESULTS: Platelet aggregation in response to collagen, adrenaline, ADP and AA were increased in the last trimester, during labour and at 1 h after delivery but decreased 24-48 h after delivery. Platelet aggregation in response to AA, collagen and adrenalin was reduced by both aspirin and dazmegrel. CONCLUSIONS: The earliest and most marked increases in platelet aggregation during normal pregnancy were found in response to AA and collagen. These platelet changes were prevented when whole blood was pre-incubated with either aspirin or dazmegrel. This suggests that enhanced production of TXA2 is responsible for increased platelet reactivity in normal pregnancy. PMID- 1606125 TI - Pregnancy following intravaginal embryo transportation. PMID- 1606126 TI - High-dose immunoglobulin in the antenatal treatment of neonatal alloimmune thrombocytopenia: case report and review. PMID- 1606128 TI - Immunohistochemistry in pelvic nodes of patients with cervical cancer. PMID- 1606127 TI - Successful twin pregnancy despite proven intraperitoneal chlamydial infection at implantation. PMID- 1606129 TI - A comparison of two endometrial samplers. PMID- 1606130 TI - Fetal blood sampling and pregnancy loss in relation to indication. PMID- 1606131 TI - Symptoms analysis for the diagnosis of genuine stress incontinence. PMID- 1606132 TI - The effect of maternal anaemia and iron deficiency on the ratio of fetal weight to placental weight. PMID- 1606133 TI - Management of prolonged pregnancy--an analysis of women's attitudes before and after term. PMID- 1606134 TI - Mutation of asparagine 229 to aspartate in thymidylate synthase converts the enzyme to a deoxycytidylate methylase. AB - The conserved Asn 229 of thymidylate synthase (TS) forms a cyclic hydrogen bond network with the 3-NH and 4-O of the nucleotide substrate dUMP. The Asn 229 to Asp mutant of Lactobacillus casei thymidylate synthase (TS N229D) has been prepared, purified, and investigated. Steady-state kinetic parameters of TS N229D show 3.5- and 10-fold increases in the Km values of CH2H4folate and dUMP, respectively, and a 1000-fold decrease in kcat. Most important, the Asp 229 mutation changes the substrate specificity of TS to an enzyme which recognizes and methylates dCMP in preference to dUMP. With TS N229D the Km for dCMP is bout 3-fold higher than for dUMP, and the Km for CH2H4folate is increased about 5 fold; however, the kcat for dCMP methylation is 120-fold higher than that for dUMP methylation. Specificity for dCMP versus dUMP, as measured by kcat/Km, changes from negligible with wild-type TS to about a 40-fold increase with TS N229D. TS N229D reacts with CH2H4folate and FdUMP or FdCMP to form ternary complexes which are analogous to the TS-FdUMP-CH2H4folate complex. From what is known of the mechanism and structure of TS, the dramatic change in substrate specificity of TS N229D is proposed to involve a hydrogen bond network between Asp 229 and the 3-N and 4-NH2 of the cytosine heterocycle, causing protonation of the 3-N and stabilization of a reactive imino tautomer. A similar mechanism is proposed for related enzymes which catalyze one-carbon transfers to cytosine heterocycles. PMID- 1606135 TI - Determination of the three-dimensional solution structure of ragweed allergen Amb t V by nuclear magnetic resonance spectroscopy. AB - Analysis of two-dimensional NMR experiments has afforded essentially complete assignment of all proton resonances in the allergenic protein Amb t V. Conformational constraints were obtained from the NMR data in three forms: interproton distances derived from NOE cross-peak intensities of NOESY spectra, torsion angle constraints derived from J-coupling constants of COSY and PE-COSY spectra, and hydrogen bond constraints derived from hydrogen-exchange experiments. Conformations of Amb t V with low constraint violations were generated using dynamic simulated annealing in the program XPLOR. The refined structures are comprised of a C-terminal alpha-helix, a short stretch of triple stranded antiparallel beta-sheet, and several loops. In addition, the cystine partners of the four disulfide linkages (for which there are no biochemical data) have been assigned. The refined structures of Amb t V will allow us to suggest surface substructures for the Amb V allergens that are likely to participate in B cell epitopes and will assist us in defining the Ia/T cell epitopes that interact with the MHC class II (or Ia) molecule and the T cell receptor leading to the induction of the immune response to Amb t V. PMID- 1606136 TI - Determination of the molecular dynamics of alamethicin using 13C NMR: implications for the mechanism of gating of a voltage-dependent channel. AB - Alamethicin is a channel-forming peptide antibiotic that produces a highly voltage-dependent conductance in planar bilayers. To provide insight into the mechanisms for its voltage dependence, the dynamics of the peptide were examined in solution using nuclear magnetic resonance. Natural-abundance 13C spin-lattice relaxation rates and 13C-1H nuclear Overhauser effects of alamethicin were measured at two magnetic field strengths in methanol. This information was interpreted using a model-free approach to obtain values for the overall correlation times as well as the rates and amplitudes of the internal motions of the peptide. The picosecond, internal motions of alamethicin are highly restricted along the peptide backbone and indicate that it behaves as a rigid helical rod in solution. The side chain carbons exhibit increased segmental motion as their distance from the peptide backbone is increased; however, these motions are not unrestricted. Methyl group dynamics are also consistent with the restricted motions observed for the backbone carbons. There is no evidence from these dynamics measurements for a hinged motion of the peptide about proline-14. Alamethicin appears to be slightly less structured in methanol than in the membrane; as a result, alamethicin is also expected to behave as a rigid helix in the membrane. This suggests that the gating of this peptide involves changes in the orientation of the entire helix, rather than the movement of a segment of the peptide backbone. PMID- 1606137 TI - Electron-transfer reactions of cytochrome f with flavin semiquinones and with plastocyanin. Importance of protein-protein electrostatic interactions and of donor-acceptor coupling. AB - Reduction of turnip ferricytochrome f by flavin semiquinones and oxidation of this ferrocytochrome f by French bean cupriplastocyanin are studied by laser flash photolysis over a wide range of ionic strengths. Second-order rate constants (+/- 15%) at extreme values of ionic strength, all at pH 7.0 and 22 degrees C, are as follows: with FMN semiquinone at 1.00 and 0.0040 M, 5.0 x 10(7) and 3.9 x 10(8) M-1 s-1; with riboflavin semiquinone at 1.00 and 0.0040 m, 1.7 x 10(8) and 1.9 x 10(8) M-1 s-1; with lumiflavin semiquinone at 1.00 and 0.0045 M, 1.8 x 10(8) and 4.5 x 10(8) M-1 s-1; with cupriplastocyanin at 1.00 and 0.100 M, 1.4 x 10(6) and 2.0 x 10(8) M-1 s-1. These reactions of cytochrome f are governed by the local positive charge of the interaction domain (the exposed heme edge), not by the overall negative charge of the protein. Lumiflavin semiquinone behaves as if it carried a small negative charge, probably because partial localization of the odd electron gives this electroneutral molecule some polarity; local charge seems to be more important than overall charge even for relatively small redox agents. The dependence of the rate constants on ionic strength was fitted to the equation of Watkins; this model recognizes the importance of local charges of the domains through which redox partners interact. There is kinetic evidence that a noncovalent complex between cytochrome f and plastocyanin exists at low ionic strength.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606139 TI - Effect of nucleotide cofactor structure on recA protein-promoted DNA pairing. 2. DNA renaturation reaction. AB - We have examined the effects of the structurally related nucleoside triphosphates, adenosine triphosphate (ATP), purine riboside triphosphate (PTP), inosine triphosphate (ITP), and guanosine triphosphate (GTP), on the recA protein promoted DNA renaturation reaction (phi X DNA). In the absence of nucleotide cofactor, the recA protein first converts the complementary single strands into unit-length duplex DNA and other relatively small paired DNA species; these initial products are then slowly converted into more complex multipaired network DNA products. ATP and PTP stimulate the conversion of initial product DNA into network DNA, whereas ITP and GTP completely suppress network DNA formation. The formation of network DNA is also inhibited by all four of the corresponding nucleoside diphosphates, ADP, PDP, IDP, and GDP. Those nucleotides which stimulate the formation of network DNA are found to enhance the formation of large recA-ssDNA aggregates, whereas those which inhibit network DNA formation cause the dissociation of these nucleoprotein aggregates. These results not only implicate the nucleoprotein aggregates as intermediates in the formation of network DNA, but also establish the functional equivalency of ITP and GTP with the nucleoside diphosphates. Additional experiments indicate that the net effect of ITP and GTP on the DNA renaturation reaction is dominated by the corresponding nucleoside diphosphates, IDP and GDP, that are generated by the NTP hydrolysis activity of the recA protein. PMID- 1606138 TI - Effect of nucleotide cofactor structure on recA protein-promoted DNA pairing. 1. Three-strand exchange reaction. AB - The structurally related nucleoside triphosphates, adenosine triphosphate (ATP), purine riboside triphosphate (PTP), inosine triphosphate (ITP), and guanosine triphosphate (GTP), are all hydrolyzed by the recA protein with the same turnover number (17.5 min-1). The S0.5 values for these nucleotides increase progressively in the order ATP (45 microM), PTP (100 microM), ITP (300 microM), and GTP (750 microM). PTP, ITP, and GTP are each competitive inhibitors of recA protein catalyzed ssDNA-dependent ATP hydrolysis, indicating that these nucleotides all compete for the same catalytic site on the recA protein. Despite these similarities, ATP and PTP function as cofactors for the recA protein-promoted three-strand exchange reaction, whereas ITP and GTP are inactive as cofactors. The strand exchange activity of the various nucleotides correlates directly with their ability to support the isomerization of the recA protein to a strand exchange-active conformational state. The mechanistic deficiency of ITP and GTP appears to arise as a consequence of the hydrolysis of these nucleotides to the corresponding nucleoside diphosphates, IDP and GDP. We speculate the nucleoside triphosphates with S0.5 values greater than 100 microM will be intrinsically unable to sustain the strand exchange-active conformational state of the recA protein during ongoing NTP hydrolysis and will therefore be inactive as cofactors for the strand exchange reaction. PMID- 1606140 TI - Solution studies on the structure of bent DNA in the cAMP receptor protein-lac DNA complex. AB - Cyclic AMP receptor protein is involved in the regulation of more than 20 genes. A step in the mechanism of activation of transcription is to induce a significant bending of the DNA upon complex formation between specific DNA and the protein. The induced DNA bending and a structure of the protein-DNA complex were studied by fluorescence energy transfer in 50 mM Tris, 1 mM EDTA, and 50 mM KCl at pH 7.8 and 20 degrees C. The symmetry of the DNA bend was estimated by measuring the efficiency of transfer between the protein and a label on either the upstream or the downstream end of a lac DNA fragment. The results show that the bend, despite the asymmetry in the DNA sequence, is symmetrical, for the fragments which length ranges from 26 to 40 bp. Using fluorescence energy transfer, the extent of DNA bending was estimated by measuring the end-to-end distance of the DNA fragment which was labeled with a donor-acceptor pair on two opposite ends. Both steady state and time-resolved measurements showed that in a 26 bp lac DNA fragment complexed with cyclic AMP receptor protein, the end-to-end distance is about 77 A which corresponds to a bending angle of 80 degrees or 100 degrees, depending on the actual contour length between the fluorophores in the free DNA fragment. The results using longer DNA fragments show no measurable amount of energy transfer; thus, it is very unlikely that the DNA completely wraps around the CRP molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606141 TI - Crystal structure of an actinidin-E-64 complex. AB - E-64, 1-(L-trans-epoxysuccinylleucylamino)-4-guanidinobutane, is a potent and highly selective irreversible inhibitor of cysteine proteases. The crystal structure of a complex of actinidin and E-64 has been determined at 1.86-A resolution by using the difference Fourier method and refined to an R-factor of 14.5%. The electron density map clearly shows that the C2 atom of the E-64 epoxide ring is covalently bonded to the S atom of the active-site cysteine 25. The charged carboxyl group of E-64 forms four H-bonds with the protein and thus may play an important role in favorably positioning the inhibitor molecule for nucleophilic attack by the active-site thiolate anion. The interaction features between E-64 and actinidin are very similar to those seen in the papain-E-64 complex; however, the amino-4-guanidinobutane group orients differently. The crystals of the actinidin-E-64 complex diffracted much better than the papain-E 64 complex, and consequently the present study provides more precise geometrical information on the binding of the inhibitor. Moreover, this study provides yet another confirmation that the binding of E-64 is at the S subsites and not at the S' subsites as has been previously proposed. The original actinidin structure has been revised using the new cDNA sequence information. PMID- 1606142 TI - Supplementation of the phosphatidyl-L-serine requirement of protein kinase C with nonactivating phospholipids. AB - The mechanism of protein kinase C (PKC) activation by phosphatidyl-L-serine (PS) is highly specific and occurs with high cooperativity [Lee, M.-H., & Bell, R. M. (1989) J. Biol. Chem. 264, 14797-14805]. To further investigate the multiplicity and specificity of PS cofactor requirement, some of the PS molecules present in Triton X-100 mixed micelles were substituted with nonactivating phospholipids devoid of required amino or carboxyl functional groups. The ability of these phospholipids to spare or reduce the mole percent of PS required was determined. Addition of phosphatidyl-(3-hydroxypropionate) (PP) or phosphatidate (PA) reduced the mole percent of PS required for maximal activity from 10 to 4 mol %, and also reduced the cooperativity of activation with PS. In contrast, phosphatidylethanolamine did not alter the dependence on PS. Phosphatidylethanol (P-Et) reduced the PS requirement to 2-4 mol % and cooperatively less efficiently than PP or PA. Phosphatidylglycerol and phosphatidylinositol resemble P-Et in their ability to reduce PS requirements and cooperativity. Therefore, it appears that the ability of phospholipids to substitute for PS in PKC activation depends on the negative charge in the phospholipid head group and the efficiency of substitution appears to be directly related to the negative charge density. The presence of two acyl groups within the phospholipid cofactor proved important since lyso-PS and lyso-PA replaced a portion of PS molecules required less efficiently than P-Et. Sodium oleate and sodium dodecyl sulfate behaved like lyso PS. When other anionic lipids are present, approximately four molecules of PS per micelle are required for maximal PKC activity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606143 TI - Different requirements for productive interaction between the active site of HIV 1 proteinase and substrates containing -hydrophobic*hydrophobic- or -aromatic*pro cleavage sites. AB - The sequence requirements for HIV-1 proteinase catalyzed cleavage of oligopeptides containing two distinct types of junctions ( hydrophobic*hydrophobic- or -aromatic*Pro-) has been investigated. For the first type of junction (-hydrophobic*hydrophobic-) the optimal residues in the P2 and P2' positions were found to be Val and Glu, respectively, in accord with recent statistical analysis of natural cleavage sites [Poorman, R. A., Tomasselli, A. G., Heinrikson, R. L., & Kezdy, F. J. (1991) J. Biol. Chem. 266, 14554-14561]. For the -aromatic*Pro- type of junction, in the specific sequence context studied here, the value of Glu in the P2' position was again observed. An explanation for the inefficient cleavage observed for peptides with the sequence -Val-Tyr*Pro- has been provided from molecular modeling of the putative enzyme-substrate complex. A significant effect upon cleavage rates due to the amino acid in the P5 position has also been documented. While lysine in the P5 position in one sequence of the -hydrophobic*hydrophobic- type produces a peptide cleaved very efficiently (kcat greater than 15 s-1 for Lys-Ala-Arg-Val-Nle*p nitrophenylalanine-P2'-Ala-Nle-NH2, for P2' = Glu, Gln, Ile, Val, or Ala), for substrates of the -aromatic*Pro- type, the P5 residue can exert either a positive or negative effect on cleavage rates. These results have again been interpreted in light of molecular modeling. We suggest that interaction of the substrate sequence on the periphery of the active site cleft may influence the match of the enzyme-substrate pair and, hence, control the efficiency of catalysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606144 TI - Crystallographic analysis of transition-state mimics bound to penicillopepsin: phosphorus-containing peptide analogues. AB - The molecular structures of three phosphorus-based peptide inhibitors of aspartyl proteinases complexed with penicillopepsin [1, Iva-L-Val-L-Val-StaPOEt [Iva = isovaleryl, StaP = the phosphinic acid analogue of statine [(S)-4-amino-(S)-3 hydroxy-6-methylheptanoic acid] (IvaVVStaPOEt)]; 2, Iva-L-Val-L-Val-L-LeuP-(O)Phe OMe [LeuP = the phosphinic acid analogue of L-leucine; (O)Phe = L-3-phenyllactic acid; OMe = methyl ester] [Iva VVLP(O)FOMe]; and 3, Cbz-L-Ala-L-Ala-L-LeuP-(O) Phe-OMe (Cbz = benzyloxycarbonyl) [CbzAALP(O)FOMe]] have been determined by X-ray crystallography and refined to crystallographic agreement factors, R ( = sigma parallel to F0 magnitude of - Fc parallel to/sigma magnitude of F0), of 0.132, 0.131, and 0.134, respectively. These inhibitors were designed to be structural mimics of the tetrahederal transition-state intermediate encountered during aspartic proteinase catalysis. They are potent inhibitors of penicillopepsin with Ki values of 1, 22 nM; 2, 2.8 nM; and 3, 1600 nM, respectively [Bartlett, P. A., Hanson, J. E., & Giannousis, P. P. (1990) J. Org. Chem. 55, 6268-6274]. All three of these phosphorus-based inhibitors bind virtually identically in the active site of penicillopepsin in a manner that closely approximates that expected for the transition state [James, M. N. G., Sielecki, A.R., Hayakawa, K., & Gelb, M. H. (1992) Biochemistry 31, 3872-3886]. The pro-S oxygen atom of the two phosphonate inhibitors and of the phosphinate group of the StaP inhibitor make very short contact distances (approximately 2.4 A) to the carboxyl oxygen atom, O delta 1, of Asp33 on penicillopepsin. We have interpreted this distance and the stereochemical environment of the carboxyl and phosphonate groups in terms of a hydrogen bond that most probably has a symmetric single-well potential energy function. The pro-R oxygen atom is the recipient of a hydrogen bond from the carboxyl group of Asp213. Thus, we are able to assign a neutral status to Asp213 and a partially negatively charged status to Asp33 with reasonable confidence. Similar very short hydrogen bonds involving the active site glutamic acid residues of thermolysin and carboxypeptidase A and the pro-R oxygen of bound phosphonate inhibitors have been reported [Holden, H. M., Tronrud, D. E., Monzingo, A. F., Weaver, L. H., & Matthews, B. W. (1987) Biochemistry 26, 8542 8553; Kim, H., & Lipscomb, W. N. (1991) Biochemistry 30, 8171-8180].(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606145 TI - Structural comparison of phosphorylated and unphosphorylated forms of IIIGlc, a signal-transducing protein from Escherichia coli, using three-dimensional NMR techniques. AB - The 18.1-kDa protein IIIGlc from Escherichia coli acts as both a phosphocarrier protein in the phosphoenolpyruvate:glycose phosphotransferase system (PTS) and as a signal-transducing protein with respect to the uptake of non-PTS sugars. Phosphorylation of IIIGlc at the N epsilon (N3) position of His-90 was effected through a regeneration system that included MgCl2, DTT, excess PEP, and catalytic amounts of Enzyme I and HPr. NH, 15N, and 13C alpha signal assignments for P IIIGlc were made through comparison of 15N-1H correlation spectra (HSQC) of uniformly 15N-labeled preparations of phosphorylated and unphosphorylated protein and through analysis of three-dimensional triple-resonance HNCA spectra of P IIIGlc uniformly labeled with both 15N and 13C. Backbone and side-chain 1H and 13C beta signals were assigned using 3D heteronuclear HCCH-COSY and HCCH-TOCSY spectra of P-IIIGlc. Using this approach, the assignments were made without reference to nuclear Overhauser effect data or assumptions regarding protein structure. The majority of NH, 15N, H alpha, and 13C alpha chemical shifts measured for P-IIIGlc were identical to those obtained for the unphosphorylated protein [Pelton, J. G., Torchia, D. A., Meadow, N. D., Wong, C.-Y., & Roseman, S. (1991) Biochemistry 30, 10043]. Those signals that exhibited shifts corresponded to residues within four segments (1) Leu-87-Gly-100, (2) Val-36-Val-46, (3) His 75-Ser-78, and (4) Ala-131-Val-138. These four segments are in close proximity to the active site residues His-75 and His-90 in the unphosphorylated protein [Worthylake, D., Meadow, N. D., Roseman, S., Liao, D., Hertzberg, O., & Remington, S.J. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 10382], and the chemical shift data provide strong evidence that if any structural changes accompany phosphorylation, they are confined to residues in these four segments. This conclusion is confirmed by comparing NOEs observed in 3D 15N/13C NOESY-HMQC spectra of the two forms of the protein. No NOE differences are seen for residues having the same chemical shifts in IIIGlc and P-IIIGlc. Furthermore, with the exception of residues Ala-76, Asp-94, and Val-96, the NOEs of residues (in the four segments) which exhibited chemical shift differences also had the same NOEs in IIIGlc and P-IIIGlc. In the case of residues Ala-76, Asp-94, and Val-96, minor differences in NOEs, corresponding to interproton distances changes of less than 1.5 A, were observed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606146 TI - Melibiose permease of Escherichia coli: mutation of histidine-94 alters expression and stability rather than catalytic activity. AB - Previous studies utilizing site-directed mutagenesis [Pourcher et al. (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 468-472] indicate that out of seven histidinyl residues in the melibiose (mel) permease of Escherichia coli, only His94 is important. The role of His94 has now been investigated by replacing the residue with Asn, Gln, or Arg. Cells expressing mel permease with Asn94 or Gln94 retain 30% or 20% of wild-type activity, respectively, and surprisingly, immunological assays demonstrate that diminished transport activity is due to a proportional reduction in the amount of permease in the membrane. Moreover, kinetic analyses of transport and ligand binding studies with right-side-out membrane vesicles indicate that both substrate recognition and turnover (kcat) are comparable in the mutant permeases and the wild-type. Mel permease with Arg in place of His94 also binds ligand and catalyzes sugar accumulation, but only when the cells are grown at 30 degrees C, and evidence is presented that Arg94 permease is inactivated at 37 degrees C. Finally, labeling studies demonstrate that expression and/or insertion of the permease, but not degradation, is strongly dependent on the amino acid present at position 94 and temperature. The findings indicate that an imidazole group at position 94 is required for proper insertion and stability of mel permease, but not for transport activity per se. Since replacement of the other six histidinyl residues in mel permease with Arg has little or no effect on transport activity, it is concluded that histidinyl residues do not play a direct role in the mechanism of this secondary transport protein. PMID- 1606147 TI - Alteration of bond-cleavage pattern in the hydrolysis catalyzed by Saccharomycopsis alpha-amylase altered by site-directed mutagenesis. AB - The 210th lysine (K) residue in the Saccharomycopsis alpha-amylase (Sfamy) molecule was replaced by arginine (R) and asparagine (N) residues by site directed mutagenesis. The influences of the replacements on the bond-cleavage pattern for several substrates were analyzed. Both mutant enzymes, K210R and K210N, cleave mainly the first glycosidic bond from the reducing end of maltotetraose (G4), while the native enzyme hydrolyzes mainly the second bond from the reducing end. We changed successfully the major cleavage point in the hydrolysis reaction of G4. The 8th subsite affinities of the K210R and K210N enzymes are calculated to be +2.52 and -0.01 kcal/mol, respectively, whereas that of the native enzyme is +3.32 kcal/mol as reported in the previous paper. These affinity values suggest that the K210 residue composes the 8th subsite, one of major subsites, and that a positively charged amino residue is necessary for the 8th subsite affinity. The K210N enzyme is found to be less active for short substrates like maltotetraose (G4) than for long substrates like amylose A (approximately G18). The reduced catalytic activity specifically for the short substrates is also attributable to the remarkable decrease in the affinity of the 8th subsite. PMID- 1606148 TI - Influence of benzo[a]pyrene diol epoxide chirality on solution conformations of DNA covalent adducts: the (-)-trans-anti-[BP]G.C adduct structure and comparison with the (+)-trans-anti-[BP]G.C enantiomer. AB - Benzo[a]pyrene (BP) is an environmental genotoxin, which, following metabolic activation to 7,8-diol 9,10-epoxide (BPDE) derivatives, forms covalent adducts with cellular DNA. A major fraction of adducts are derived from the binding of N2 of guanine to the C10 position of BPDE. The mutagenic and carcinogenic potentials of these adducts are strongly dependent on the chirality at the four asymmetric benzylic carbon atoms. We report below on the combined NMR-energy minimization refinement characterization of the solution conformation of (-)-trans-anti-[BP]G positioned opposite C and flanked by G.C base pairs in the d(C1-C2-A3-T4-C5 [BP]G6-C7-T8-A9-C10-C11).d(G12-G13-T14++ +-A15-G16-C17- G18-A19-T20-G21-G22) duplex. Two-dimensional NMR techniques were applied to assign the exchangeable and non-exchangeable protons of the benzo[a]pyrenyl moiety and the nucleic acid in the modified duplex. These results establish Watson-Crick base pair alignment at the [BP]G6.C17 modification site, as well as the flanking C5.G18 and C7.G16 pairs within a regular right-handed helix. The solution structure of the (-) trans-anti-[BP]G.C 11-mer duplex has been determined by incorporating intramolecular and intermolecular proton-proton distances defined by lower and upper bounds deduced from NOE buildup curves as constraints in energy minimization computations. The BP ring spans both strands of the duplex in the minor groove and is directed toward the 3'-end of the modified strand in the refined structure. One face of the BP ring of [BP]G6 stacks over the C17 residue across from it on the partner strand while the other face is exposed to solvent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606149 TI - Dynamics of methyl groups in proteins as studied by proton-detected 13C NMR spectroscopy. Application to the leucine residues of staphylococcal nuclease. AB - This paper describes the application of recently developed nuclear magnetic resonance (NMR) pulse sequences to obtain information about the internal dynamics of isotopically enriched hydrophobic side chains in proteins. The two-dimensional spectra provided by the pulse sequences enable one to make accurate measurements of nuclear Overhauser effects (NOE) and longitudinal (T1) and transverse (T2) relaxation times of enriched methyl carbons in proteins. Herein, these techniques are used to investigate the internal dynamics of the 11 leucine side chains of staphylococcal nuclease (SNase), a small enzyme having Mr = 16.8K, in the absence and presence of ligands thymidine 3',5'-bisphosphate (pdTp) and Ca2+. We report the synthesis of [5,5'-13C2]leucine, the preparation of SNase containing the labeled leucine, the sequential assignment of the leucine methyl carbons and protons in the liganded and unliganded proteins, and the measurement of the 13C T1, T2, and NOE values for the SNase leucine methyl carbons. Analysis of the relaxation parameters using the formalism of Lipari and Szabo shows that the internal motions of the leucine methyl carbons are characterized by effective correlation times tau f (5-80 ps) and tau s (less than 2 ns). The fast motion is identified with the rapid rotation of the methyl group about the C gamma-C delta bond axis, while the slow motion is associated with reorientation of the C gamma C delta bond axis itself. The mean squared order parameters associated with the latter motion, Ss2, lie in the range 0.34-0.92. The values of Ss2 correlate reasonably well with the temperature factors of the leucine methyl carbons obtained from the crystal structures, but some are smaller than anticipated on the basis of the fact that nearly all leucine methyl carbons are buried and have temperature factors no larger than that of the leucine backbone atoms. Five leucine residues in liganded SNase and eight in unliganded SNase have values of Ss2 less than 0.71. These order parameters correspond to large amplitude motions (angular excursions of 27-67 degrees) of the C gamma-C delta bond axis. These results indicate that, in solution, the internal motions of the leucine side chains of SNase are significantly larger than suggested by the X-ray structures or by qualitative analysis of NOESY spectra. Comparison of Ss2 values obtained from liganded and unliganded SNase reveals a strong correlation between delta Ss2 and distance between the leucine methyl carbon and the ligands.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606150 TI - 1H NMR and NOE studies of the purple acid phosphatases from porcine uterus and bovine spleen. AB - The diiron active sites of the purple acid phosphatases from porcine uterus (also called uteroferrin, Uf) and bovine spleen (BSPAP) and their complexes with tungstate are compared by 1H NMR and NOE techniques. The paramagnetically shifted features of the 1H NMR spectrum of reduced BSPAP are similar to those of reduced Uf, while the spectra of the tungstate complexes are almost identical. These observations suggest that the two active sites are quite similar, in agreement with the greater than 90% sequence homology found in the two enzymes. Nuclear Overhauser effect (NOE) experiments on the His N-H resonances show that the Fe(III)-His residue is N epsilon-coordinated, while the Fe(II)-His is H delta coordinated in both enzymes. On the basis of the above NMR and NOE results, our previously proposed model for the dinuclear iron active site of Uf [Scarrow, R. C., Pyrz, J. W., & Que, L., Jr. (1990) J. Am. Chem. Soc. 112, 657-665] is corroborated, refined, and found to represent the diiron center of BSPAP as well. PMID- 1606151 TI - Backbone dynamics of calmodulin studied by 15N relaxation using inverse detected two-dimensional NMR spectroscopy: the central helix is flexible. AB - The backbone dynamics of Ca(2+)-saturated recombinant Drosophila calmodulin has been studied by 15N longitudinal and transverse relaxation experiments, combined with 15N(1H) NOE measurements. Results indicate a high degree of mobility near the middle of the central helix of calmodulin, from residue K77 through S81, with order parameters (S2) in the 0.5-0.6 range. The anisotropy observed in the motion of the two globular calmodulin domains is much smaller than expected on the basis of hydrodynamic calculations for a rigid dumbbell type structure. This indicates that, for the purposes of 15N relaxation, the tumbling of the N-terminal (L4-K77) and C-terminal (E82-S147) lobes of calmodulin is effectively independent. A slightly shorter motional correlation time (tau c approximately 6.3 ns) is obtained for the C-terminal domain compared to the N-terminal domain (tau c approximately 7.1 ns), in agreement with the smaller size of the C-terminal domain. A high degree of mobility, with order parameters of approximately 0.5, is also observed in the loop that connects the first with the second EF-hand type calcium binding domain and in the loop connecting the third and fourth calcium binding domain. PMID- 1606152 TI - Assignment of amide 1H and 15N NMR resonances in detergent-solubilized M13 coat protein: a model for the coat protein dimer. AB - The major coat protein of the filamentous coliphage M13 is a 50-residue integral membrane protein. Detergent-solubilized M13 coat protein is a promising candidate for structure determination by nuclear magnetic resonance methods as the protein can be prepared in large quantities and the protein-containing micelle is reasonably small. Under the conditions of our experiments, SDS-bound coat protein exists as a dimer with an apparent molecular weight of 27,000. Broad lines and poor resolution in the 1H spectrum have led us to adopt an 15N-directed approach, in which the coat protein was labeled both uniformly with 15N and selectively with [alpha-15N]alanine, -glycine, -valine, -leucine, -isoleucine, phenylalanine, -lysine, -tyrosine, and -methionine. Nitrogen resonances were assigned as far as possible using carboxypeptidase digestion, double-labeling, and an independent knowledge of the amide proton exchange rates determined from neighboring assigned 13C-labeled carbonyl carbons. 1H/15N heteronuclear multiple quantum coherence (HMQC) spectroscopy of both uniform and site-selectively-labeled proteins subsequently correlated amide nitrogen with amide proton chemical shifts, and the assignments were completed sequentially from homonuclear NOESY and HMQC-NOESY spectra. The most slowly exchanging amide protons were shown to occur in a continuous stretch extending from methionine-28 to phenylalanine-42. This sequence includes most of the resonances of the hydrophobic core, although it is shifted toward the C-terminal end of the protein. Strong NH to NH (i,i+1) nuclear Overhauser enhancements are a feature of the coat protein, which appears to be largely helical. Between 20 and 25 residues give rise to 2 juxtaposed resonances which can be seen clearly in the HMQC spectrum of uniform 15N-labeled coat protein. These residues are concentrated in a region extending from the beginning of the membrane-spanning sequence through to the disordered region near the C terminus. We propose that dodecyl sulfate-bound M13 coat protein consists of two independent domains, an N-terminal helix which is in a state of moderately fast dynamic flux and a long, stable, C-terminal membrane-spanning helix, which undergoes extensive interactions with a second monomer. Amide 1H chemical shifts are consistent with this picture; in addition, a marked periodicity is observed at the C-terminal end of the molecule. PMID- 1606153 TI - X-ray absorption studies of the Cu-dependent phenylalanine hydroxylase from Chromobacterium violaceum. Comparison of the copper coordination in oxidized and dithionite-reduced enzymes. AB - The coordination chemistry of the Cu sites of phenylalanine hydroxylase (PAH) from Chromobacterium violaceum has been studied by X-ray absorption spectroscopy (XAS). The EXAFS of the Cu(II) form of the enzyme resembles that of other non blue copper proteins such as plasma amine oxidases and dopamine-beta-hydroxylase and is characteristic of a mixed N/O coordination shell containing histidine ligation. Detailed simulations of the raw EXAFS data have been carried out using full curved-wave restrained refinement methodologies which allow imidazole ligands to be treated as structural units. The results suggest a Cu(II) coordination of two histidines and two additional O/N-donor groups. A reasonable fit to both data sets can be obtained by assuming that the non-imidazole first shell donor atoms are derived from solvent (H2O or OH-). The EXAFS of the reduced enzyme shows major differences. The amplitude of the first shell in the Fourier transform is only 50% of that of the oxidized enzyme, indicative of a substantial reduction in coordination number. In addition, the first shell of the transform is split into two components. Simulations of the reduced data can be obtained by either two histidines at a long distance of 2.08 A and an O ligand at a short distance of 1.88 A or two histidines at a short distance of 1.90 A and one second row scatterer such as S or Cl at 2.20 A. Comparison of absorption edge data on the reduced enzyme with data from Cu(I) bis- and tris(1,2-dimethylimidazole) complexes suggests a pseudo-three-coordinate structure. PMID- 1606154 TI - A ligand-induced conformational change in the estrogen receptor is localized in the steroid binding domain. AB - Upon binding estrogen, the estrogen receptor (ER) is proposed to undergo some form of conformational transition leading to increased transcription from estrogen-responsive genes. In vitro methods used to study the transition often do not separate heat-induced effects on the ER from estrogen-induced effects. The technique of affinity partitioning with PEG-palmitate was used to study the change in the hydrophobic surface properties of the ER upon binding ligand with and without in vitro heating. Upon binding estradiol (E2), the full-length rat uterine cytosolic ER undergoes a dramatic decrease in surface hydrophobicity. The binding of the anti-estrogen 4-hydroxytamoxifen (4-OHT) results in a similar decrease in surface hydrophobicity. These effects are independent of any conformational changes induced by heating the ER to 30 degrees C for 45 min. The use of the human ER steroid binding domain overproduced in Escherichia coli (ER C) and the trypsin-generated steroid binding domain from rat uterine cytosolic ER demonstrates that the decrease in surface hydrophobicity upon binding E2 or 4-OHT is localized to the steroid binding domain. Gel filtration analysis indicates that the change in surface hydrophobicity upon binding ligand is an inherent property of the steroid binding domain and not due to a ligand-induced change in the oligomeric state of the receptor. The decrease in surface hydrophobicity of the steroid binding domain of the ER upon binding E2 or 4-OHT represents an early and possibly a necessary event in estrogen action and may be important for "tight" binding of the ER in the nucleus. PMID- 1606155 TI - Calibration of the parallax fluorescence quenching method for determination of membrane penetration depth: refinement and comparison of quenching by spin labeled and brominated lipids. AB - We previously introduced the "parallax" method, which uses fluorescence quenching by spin-labeled lipids in order to measure the depth of molecules within a membrane [Chattopadhyay, A., & London, E. (1987) Biochemistry 26, 39-45]. In this report the accuracy of this method is established by comparison of spin-label quenching to that obtained using brominated lipids. To accomplish this, the fluorescent molecules used were a fatty acid labeled with a carbazole buried deeply within the acyl chain region of the membrane, an acyl-Trp with the Trp residue residing near the polar membrane region, and cytochrome b5, which has Trp residues in its membrane-inserted region. The depths calculated from the amount of bromine quenching agreed with those determined using parallax analysis. This indicates that the depth reported by parallax analysis is accurate and that the spin labels residue very close to their predicted locations in the membrane. Furthermore, there was good agreement when parallax analysis was applied both to quenching by brominated and spin-labeled molecules, suggesting that the analysis is valid in both cases. The effect that different distributions and motions of fluorophores and quenchers would have on parallax analysis was also examined. For uniform distributions of quenchers or fluorophores over a range of depths, it was found that the analysis reports the average fluorophore depth. In addition, experimental data suggest that motional effects do not significantly alter the measured depths. This is consistent with the motions during the short excited state lifetime of the fluorophores being relatively small and/or relatively isotropic. PMID- 1606156 TI - Determination of the location of fluorescent probes attached to fatty acids using parallax analysis of fluorescence quenching: effect of carboxyl ionization state and environment on depth. AB - In this report, parallax analysis of fluorescence quenching (see the preceding paper in this issue) was used to determine the location (depth) of anthroyloxy and carbazole probes attached to model membrane inserted fatty acids. A monotonic increase in depth was found as the number of carbon atoms between the attachment site of the probe and the fatty acyl carboxyl group is increased. It was also found that depth is sensitive to pH, with an increase in probe depth upon protonation of the fatty acid carboxyl group of around 0.5-2.5 A, depending on probe location and identity. This result shows that carboxyl protonation causes an increase in depth all along a fatty acid chain. In addition, it indicates that parallax analysis is very sensitive to small changes in depth. At a given pH, no significant change in probe depth was observed in vesicles containing anionic phospholipid or at various ionic strengths, suggesting these parameters do not strongly regulate fatty acyl chain location. It was also found that there is a decrease of the apparent depth of each of the fatty acyl attached probes both at longer excitation wavelengths and at longer emission wavelengths. This is consistent with there being a distribution of depth for each fluorophore, with shallower fluorophore dominating the fluorescence at red-shifted wavelengths. Solvent relaxation effects also appear to contribute to this wavelength dependence. PMID- 1606157 TI - Time-resolved ultraviolet resonance Raman studies of protein structure: application to bacteriorhodopsin. AB - Time-resolved ultraviolet resonance Raman spectra of bacteriorhodopsin are used to study protein structural changes on the nanosecond and millisecond time scales. Excitation at 240 nm is used to selectively enhance vibrational scattering from tyrosine so that changes in its hydrogen bonding and protonation state can be examined. Both nanosecond and millisecond UV Raman difference spectra indicate that none of the tyrosine residues change ionization state during the BR----K and BR----M transitions. However, intensity changes are observed at 1172 and 1615 cm-1 in the BR----M UV Raman difference spectra. The 1615-cm-1 feature shifts down 25 cm-1 in tyrosine-d4-labeled BR, consistent with its assignment as a tyrosine vibration. The intensity changes in the BR----M UV Raman difference spectra most likely reflect an increase in resonance enhancement that occurs when one or more tyrosine residues interact more strongly with a hydrogen-bond acceptor in M412. The frequency of the v7a feature (1172 cm-1) in the BR----M UV Raman difference spectra supports this interpretation. The proximity of Tyr-185 and Asp-212 in the retinal binding pocket suggests that deprotonation of the Schiff base in M412 causes Tyr-185 to stabilize ionized Asp 212 by forming a stronger hydrogen bond. PMID- 1606158 TI - Novel modification of glycosphingolipids by long-chain cyclic acetals: isolation and characterization of plasmalocerebroside from human brain. AB - A glycosphingolipid component of human brain, having long-chain cyclic acetals, has been isolated and characterized. This compound incorporates a novel type of natural glycan modification, in which a long-chain aliphatic aldehyde is conjugated through a cyclic acetal (plasmal) linkage to the galactosyl moiety of cerebroside. In addition to components normally observed by gas chromatography mass spectrometry (GC-MS) following methanolysis of cerebroside (fatty acid methyl esters, methyl alpha- and beta-galactosides, sphingosine), this compound produced 16:0, 18:0, and 18:1 fatty aldehydes, unequivocally identified as their enol methyl ether derivatives. Results of positive ion fast atom bombardment mass spectrometry (FAB-MS) of the native compound, and GC-MS of partially methylated hexitol acetates derived from the permethylated derivative, were consistent with structures of galactocerebroside having 3,4- and 4,6-linked cyclic plasmal substituents, as shown. [formula: see text] PMID- 1606159 TI - Toxoplasma gondii stimulates the release of 13- and 9-hydroxyoctadecadienoic acids by human platelets. AB - We have recently demonstrated a novel cytotoxic effect of human platelets against Toxoplasma gondii and a role for thromboxane (TX) in this process (Yong et al., 1991). We now report on the spectrum of lipid mediators released by human platelets after interaction with T. gondii. In addition to TXB2, human platelets after incubation with T. gondii for 90 min released 12-hydroxyheptadecatrienoic acid (12-HHT), 12-hydroxyeicosatetraenoic acid (12-HETE), and an unidentified peak (UVmax 234 nm) as determined by reverse-phase high-performance liquid chromatography. Thermospray-liquid chromatography/mass spectrometry analysis and straight-phase HPLC identified the unknown peak as a mixture of 13 hydroxyoctadecadienoic acid (HODE) and 9-HODE. Radiolabeling studies with [14C]linoleic acid indicated that the platelets were the cellular source of the octadecanoids with 13-HODE (87.7%) greater than 9-HODE (12.3%). Inhibitor studies with indomethacin indicated that 13-HODE was a lipoxygenase product and 9-HODE was a cyclooxygenase product of linoleic acid. Thus, Toxoplasma-stimulated platelets release oxygenated products of both arachidonic acid and linoleic acid which may be important in the host response to T. gondii infection. PMID- 1606160 TI - Conformational equilibrium of an enzyme catalytic site in the allosteric transition. AB - The dynamic equilibrium of a catalytic site between active and inactive conformations, the missing link between the structure and function of allosteric enzymes, was identified using protein engineering and NMR techniques. Kinetic analyses of the wild-type and three mutants of Thermus L-lactate dehydrogenase established that the allosteric property of the enzyme is associated with a concerted transition between the high-affinity (R) and low-affinity (T) states. By introducing mutations, we prepared an enzyme in which the R and T states were balanced. The conformation of the enzyme-bound coenzyme, NAD+, which interacts directly with the substrate, was analyzed using NMR spectroscopy. NAD+ bound to the mutant enzyme was in a conformational mixture of the active and inactive forms, while NAD+ took on predominantly one of the two forms when it was bound to the other enzymes we had analyzed. We interpret this to mean that the catalytic site is in equilibrium between the two conformations. The ratio of the conformers of each enzyme agreed with the [T]/[R] ratio as determined by kinetic analyses. Therefore, it is the identified conformational equilibrium of the catalytic site that governs the allosteric regulation of the enzyme activity. PMID- 1606161 TI - Analysis of ground-state and transition-state effects in enzyme catalysis. AB - "The entire and sole source of catalytic power is the stabilization of the transition state; reactant-state interactions are by nature inhibitory and only waste catalytic power". So reads a literature quote expressing the current view on enzyme catalysis proposed by Pauling over 40 years ago. Its validity is now examined by means of a "split-site" model in which an active site is subdivided into a region of binding and a region of reaction. Analysis of the resulting free energy levels clarifies several points of confusion regarding the nature of enzyme catalysis, including why enzyme/substrate complexes form if, indeed, they only "waste catalytic power". Circumstances are defined in which an evolving enzyme can both lower Km (i.e., enhance substrate binding) and improve the forward catalytic rate while never meddling with the transition structure at the reactive site. It is argued that this process is most advantageously viewed as a substrate destabilization embodying "conserved" interactions at the binding region. Classical transition-state stabilization and an "anti-Pauling" effect are both capable of inducing rate accelerations. In certain circumstances, the latter can predominate as it does with many enzyme-like intramolecular reactions. Behavioral modes discussed herein are applicable to the chemistry of catalytic host/guest and enzyme systems. PMID- 1606162 TI - Reaction pathway for inhibition of blood coagulation factor Xa by tick anticoagulant peptide. AB - The reaction pathway for inhibition of human factor Xa (fXa) by recombinant tick anticoagulant peptide (rTAP) was studied by stopped-flow fluorometry. In the presence of the fluorogenic substrate N-tert-butyloxycarbonyl-L-isoleucyl-L glutamylglycyl-L-arginyl-7-amido-4 - methylcoumarin (B-IEGR-AMC) and under pseudo first-order conditions, inhibition appears to occur via a two-step process. Initially, a weak enzyme-inhibitor complex forms with a dissociation constant (Ki) of 68 +/- 6 microM. The initial complex then rearranges to a more stable fXa rTAP complex with a rate constant (k2) of 123 +/- 5 s-1. The apparent second order rate constant (k2/Ki) describing formation of the stable complex is (1.8 +/ 0.2) x 10(6) M-1 s-1. Studies of the reaction of rTAP with fXa in the presence of the fluorescent active-site probe p-amino-benzamidine (P) revealed a reaction pathway wherein rTAP initially binds to the fXa-P complex in a two-step process prior to displacing P from the active site. These results indicate that rTAP can bind fXa via a site distinct from the active site (an exosite). The subsequent displacement of P from the active site of fXa by rTAP exhibits a dependence on the concentration of P, indicating that rTAP is locked into the active site in a third step.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606163 TI - Isolated oligopurine tracts do not significantly affect the binding of DNA to nucleosomes. AB - Nucleosomal-length DNA was constructed to contain one of two 10 bp oligopurine oligopyrimidine sequences, either d(A10.T10) or d(G10.C10). The 146 base pair (bp) sequences were then each tandemly cloned. This allowed for the production of circularly-permuted sequence variants in which the oligopurine tract was located at eight different positions. The permuted sequences were then assayed for their ability to reconstitute into nucleosomes by competitive reconstitution. The results of the assay indicate that the free energy of nucleosome formation differs only by several tenths of a kilocalorie per mole for an oligopurine tract at any position along the DNA, including the central dyad region. PMID- 1606164 TI - Regulation of the functional expression of hexose transporter GLUT-1 by glucose in murine fibroblasts: role of lysosomal degradation. AB - The nature of the membrane compartments involved in the regulation by glucose of hexose transport is not well defined. The effect of inhibitors of lysosomal protein degradation on hexose transport (i.e., uptake of [3H]-2-deoxy-D-glucose) and hexose transporter protein GLUT-1 (i.e., immunoblotting with antipeptide serum) in glucose-fed and -deprived cultured murine fibroblasts (3T3-C2 cells) was studied. The acidotropic amines chloroquine (20 microM) and ammonium chloride (10 mM) cause accumulation (both approximately 4-fold) of GLUT-1 protein and a small increase (both approximately 25%) in hexose transport in glucose-fed fibroblasts (24 h). The endopeptidase inhibitor, leupeptin (100 microM) causes accumulation (approximately 4-fold) of GLUT-1 protein in glucose-fed fibroblasts (24 h) without changing hexose transport (less than or equal to 5%). These agents do not greatly alter the electrophoretic mobility of GLUT-1. Neither chloroquine nor leupeptin augment the glucose deprivation (24 h) induced increases in hexose transport (approximately 4-fold) and GLUT-1 content (approximately 7-fold). In contrast, chloroquine or leupeptin diminish the reversal by glucose refeeding of the glucose deprivation induced accumulation of GLUT-1 protein but fail to alter the return of hexose transport to control levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606165 TI - The MgATP-binding site on chicken gizzard myosin light chain kinase remains open and functionally competent during the calmodulin-dependent activation inactivation cycle of the enzyme. AB - An ATP-like affinity labeling reagent, 5'-[p-(fluorosulfonyl)benzoyl]adenosine (FSBA), was used to probe the MgATP-binding site of smooth muscle myosin light chain kinase from chicken gizzard (smMLCK) and its calmodulin (CaM) complex. Native smMLCK has an absolute requirement for the binding of the calcium complex of CaM for expression of its catalytic activity. FSBA reacted with smMLCK-CaM and with the CaM-free, inactive enzyme as well. Both reactions were dependent on time and FSBA concentration. Reaction was accompanied by the incorporation of covalently bound [14C]FSBA into smMLCK protein at a molar ratio of approximately 1:1 in each case. p-(Fluorosulfonyl)benzoic acid, an analogue of FSBA lacking the adenosine targeting group, did not react at a significant rate with either form of smMLCK. Reaction of CaM-free and CaM-bound smMLCK with FSBA displayed saturation kinetics. The first-order rate constants for the conversion of the reversible, noncovalent enzyme-FSBA complex to form the irreversibly inhibited, covalently modified enzyme were similar for both smMLCK and smMLCK-CaM, 0.15 and 0.07 min-1, respectively. The concentrations of FSBA yielding the half-maximal rate of inactivation, KI, were essentially identical--0.65 and 0.64 mM, respectively--for smMLCK and smMLCK-CaM. MgATP, but not MgGTP or a substrate peptide, potently inhibited reaction with FSBA. Inhibition by MgATP was competitive. The measured inhibitory constant for MgATP was essentially the same- 33 versus 34 microM--for both smMLCK and smMLCK-CaM. It therefore is concluded that the MgATP-binding site on smMLCK remains accessible and recognizable as such when the enzyme becomes inactivated upon dissociation of CaM. PMID- 1606166 TI - Aminonaphthalenesulfonamides, a new class of modifiable fluorescent detecting groups and their use in substrates for serine protease enzymes. AB - A series of new compounds, 6-amino-1-naphthalenesulfonamides (ANSN), were used as fluorescent detecting groups for substrates of amidases. These compounds have a high quantum fluorescent yield, and the sulfonyl moiety permits a large range of chemical modification. Fifteen ANSN substrates with the structure (N alpha-Z)Arg ANSNR1R2 were synthesized and evaluated for their reactivity with 8 proteases involved in blood coagulation and fibrinolysis. Thrombin, activated protein C, and urokinase rapidly hydrolyzed substrates with monosubstituted sulfonamide moieties (R1 = H). The maximum rate of substrate homologue). The hydrolysis rates for substrates with branched substituents were slower than their linear analogues. Monosubstituted (N alpha-Z)Arg-ANSNR1R2 possessing cyclohexyl or benzyl groups in the sulfonamide moiety were hydrolyzed by these three enzymes at rates similar to that of the n-butyl homologue (except the cyclohexyl compound for u-PA). Factor Xa rapidly hydrolyzed substrates with short alkyl chains, especially when R1 = R2 = CH3 or C2H5. Lys-plasmin and rt-PA demonstrated low activity with these compounds, and the best results were accomplished for monosubstituted compounds when R2 = benzyl (for both enzymes). Factor VIIa and factor IXa beta exhibited no activity with these substrates. A series of 14 peptidyl ANSN substrates were synthesized, and their reactivity for the same 8 enzymes was evaluated. Thrombin, factor Xa, APC, and Lys-plasmin hydrolyzed all of the substrates investigated. Urokinase, rt-PA, and factor IXa beta exhibited reactivity with a more limited group of substrates, and factor VIIa hydrolyzed only one compound (MesD-LGR-ANSN(C2H5)2). The substrate ZGGRR-ANSNH (cyclo-C6H11) showed considerable specificity for APC in comparison with other enzymes (kcat/KM = 19,300 M-1 s-1 for APC, 1560 for factor IIa, and 180 for factor Xa). This kinetic advantage in substrate hydrolysis was utilized to evaluate the activation of protein C by thrombin in a continuous assay format. Substrate (D-LPR ANSNHC3H7) was used to evaluate factor IX activation by the factor VIIa/tissue factor enzymatic complex in a discontinuous assay. A comparison between the commercially available substrate chromozyme TH (p-nitroanilide) and the ANSN substrate with the same peptide sequence (TosGPR) demonstrated that aminonaphthalenesulfonamide increased the specificity (kcat/KM) of substrate hydrolysis by thrombin more than 30 times, with respect to factor Xa substrate hydrolysis. PMID- 1606167 TI - Conformational properties of the G.G mismatch in d(CGCGAATTGGCG)2 determined by NMR. AB - The conformational properties of the DNA duplex d(CGCGAATTGGCG)2, which contains two noncomplementary G.G base pairs, have been examined in aqueous solution by 1H and 31P NMR as a function of temperature. The G.G mismatch is highly destabilizing, with a Tm value 35 K below that observed for the native EcoRI dodecamer. The dodecamer appears symmetric in the NMR spectra and exists largely as an average B-type DNA conformation. However, the 1H and 31P NMR spectra give evidence of considerable conformational heterogeneity at the mismatched nucleotides and their nearest neighbors, which increases with increasing temperature. There is no evidence for a significant population of the syn purine conformation. The imino protons of the mispaired bases G4 and G9 are degenerate, resonate at high field, and exchange readily with solvent. These results indicate that the mispaired bases are only weakly hydrogen-bonded and are only partially stacked into the helix. On raising the temperature, the duplex shows increasing exchange between two or more conformations originating from the mismatch sites. However, these additional conformations maintain their Watson-Crick hydrogen bonding. The increase in chemical exchange is consistent with a quasimelting process for which the G.G sites provide local nuclei. Extensive modeling studies by dynamic annealing have confirmed that the G(anti).G(anti) conformation is favored and that the mispairs are poorly stacked within the helix. The results explain both the poor thermal stability and low hypochromicity of this duplex. PMID- 1606168 TI - A critical review of comprehensive health screening in adolescents. PMID- 1606169 TI - Activator proteins and topology of lysosomal sphingolipid catabolism. AB - The lysosomal degradation of several sphingolipids by acid hydrolases is dependent on small non-enzymic cofactors, called sphingolipid activator proteins some of which have been identified as sphingolipid binding proteins. This review summarizes the information available on the structure, function, biosynthesis, gene organization and pathobiochemistry of the known sphingolipid activator proteins. It also offers models for their mode of action and for the topology of lysosomal digestion of glycolipids. PMID- 1606170 TI - Isolation and partial characterization of lipoprotein A-II (LP-A-II) particles of human plasma. AB - High density lipoproteins (HDL) consist of a mixture of chemically and functionally distinct families of particles defined by their characteristic apolipoprotein (Apo) composition. The two major lipoprotein families are lipoprotein A-I (LP-A-I) and lipoprotein A-I:A-II (LP-A-I:A-II). This study describes the isolation of a third minor HDL family of particles referred to as lipoprotein A-II (LP-A-II) because it lacks ApoA-I and contains ApoA-II as its main or sole apolipoprotein constituent. Because ApoA-II is an integral protein constituent of three distinct lipoprotein families (LP-A-I:A-II, LP-A-II: B:C:D:E and LP-A-II), LP-A-II particles were isolated from whole plasma by sequential immunoaffinity chromatography on immunosorbers with antisera to ApoA-II, ApoB and ApoA-I, respectively. In normolipidemic subjects, the concentration of LP-A-II particles, based on ApoA-II content, is 4-18 mg/dl accounting for 5-20% of the total ApoA-II not associated with ApoB-containing lipoproteins. The lipid composition of LP-A-II particles is characterized by low percentage of triglycerides and cholesterol esters and a high percentage of phospholipids in comparison with lipid composition of LP-A-I and LP-A-II: A-II. The major part of LP-A-II particles contain ApoA-II as the sole apolipoprotein constituent; however, small subsets of LP-A-II particles may also contain ApoD and other minor apolipoproteins. The lipid/protein ratio of LP-A-II is higher than those of LP-A I and LP-A-I:A-II. In homozygous ApoA-I and ApoA-I/ApoC-III deficiencies, LP-A-II particles are the only ApoA-containing high density lipoprotein with levels found to be within the same range (7-13 mg/dl) as those of normolipidemic subjects. However, in contrast to normal LP-A-II, their lipid composition is characterized by higher percentages of triglycerides and cholesterol esters and a lower percentage of phospholipids and their apolipoprotein composition by the presence of ApoC-peptides and ApoE in addition to ApoA-II and ApoD. These results show that LP-A-II particles are a minor HDL family and suggest that, in the absence of ApoA-I-containing lipoproteins, they become an efficient acceptor/donor of ApoC peptides and ApoE required for a normal metabolism of triglyceride-rich lipoproteins. Their other possible functional roles in lipid transport remain to be established in future experiments. PMID- 1606171 TI - Desaturation of linoleic acid in the small bowel is increased by short-term fasting and by dietary content of linoleic acid. AB - The rate of desaturation of linoleic acid (18:2(n - 6)) and level of arachidonic acid (20: 4(n - 6)) in mucosal microsomes from small intestine of rats fasted for 24 h or fed diets of different fatty acid composition was examined. Fasting or feeding a diet high in linoleic acid increased delta 6-desaturase activity, a rate-limiting enzyme in the arachidonic acid biosynthetic pathway in the jejunum. After fasting, delta 6-desaturase activity was also enhanced in the ileum. Feeding a diet rich in n - 3 fatty acids had no significant effect on delta 6 desaturase activity in jejunal or ileal mucosal microsomes. Following fasting, arachidonic acid content of microsomal total phospholipids increased in the jejunum with a concomitant decrease in linoleic acid content. Arachidonic acid and 18:2(n - 6) concentration remained unchanged in ileal microsomes after short term food withdrawal. Feeding a diet containing n - 3 fatty acids lowered the content of 20:4(n - 6) and increased 20:5(n - 3) and 22:6(n - 3) levels in both jejunal and ileal microsomes. These data indicate that the level of 20:4(n - 6) and the biosynthesis of 20:4(n - 6) by desaturation-chain elongation of 18:2(n - 6) in the rat enterocyte responds rapidly to change in physiological conditions such as fasting and dietary fat composition. PMID- 1606172 TI - Effect of pulmonary surfactant protein B (SP-B) and calcium on phospholipid adsorption and squeeze-out of phosphatidylglycerol from binary phospholipid monolayers containing dipalmitoylphosphatidylcholine. AB - The pulsating bubble technique was used to study the surface activity of binary phospholipid mixtures containing dipalmitoyl-phosphatidylcholine (DPPC) and an unsaturated acidic phospholipid such as egg phosphatidylglycerol (egg PG), 1 palmitoyl-2-oleoyl-PG (POPG) or egg phosphatidic acid (egg PA) in the presence of surfactant-associated protein B (SP-B) and calcium. The relative surface activities were DPPC/egg PG/SP-B (7:3:1%) greater than DPPC/POPG/SP-B (7:3:1%) greater than DPPC/egg PA/SP-B (7:3:1%). The Wilhelmy surface plate technique was utilized to investigate the interaction between pure SP-B in the bulk phase (0.9% NaCl/1.5 mM CaCl2) and preformed DPPC or phosphatidylglycerol (PG) monolayers. Although SP-B injected into the bulk phase reduces the surface tension of a clean surface, no evidence was obtained for the insertion of SP-B into surface monolayers at equilibrium surface tension. Surface radioactivity measurements and the Wilhelmy surface plate technique were also used to study the potential interactions between liposomes of DPPC/POPG (7:3) with or without SP-B and surface monolayers of [14C]DPPC or [14C]POPG. No exchange of phosphatidylcholine (PC) or PG was found between the monolayer and liposomes. We also compared the adsorption of pure POPG or 1-palmitoyl-2-oleoyl- phosphatidylcholine (POPC) and binary mixed liposomes with DPPC in the presence or absence of SP-B and calcium. DPPC/POPG/SP-B (7:3:1%) was found to be more surface active than pure POPG plus 1% SP-B in the presence of calcium. Injection of SP-B into the bulk phase promoted the adsorption of DPPC/POPG liposomes to a greater extent than POPG liposomes. The enhanced adsorption was dependent on the presence of calcium. In contrast to PG, DPPC/POPC/SP-B (7:3:1%) was less surface active than pure POPC plus 1% SP-B either in the presence or absence of calcium. Our findings suggested that the molecular composition and organization of mixed monolayers play an important role in the surface activity of the surfactant. PMID- 1606173 TI - Biliary excretion of chenodeoxycholyllysylrhodamine in Wistar rats: a possible role of a bile acid as a carrier for drugs. AB - The effect on biliary excretion of rhodamine after its conjugation to give chenodeoxycholyl-lysyl-rhodamine (cheno-lys-R) was studied in male Wistar rats. Following its intravenous injection via the jugular vein of animals cheno-lys-R was efficiently excreted into bile with a peak biliary excretion of 31.6 +/- 1.2% dose 5 min-1 and a cumulative biliary excretion of 96.4 +/- 2.0% in 30 min of the total dose administered. Unlike cheno-lys-R, rhodamine had a poor biliary excretion of 1.0 +/- 0.1% dose 5 min-1 and a cumulative biliary excretion of 3.3 +/- 0.6% in 30 min. Cheno-lys-R had a short plasma half-life (t1/2 alpha) of 4.0 +/- 0.5 min, whereas free rhodamine had a longer half life (t1/2 alpha) of 82.1 +/- 1.4 min. The plasma clearances of cheno-lys-R and rhodamine were 41.2 +/- 6.5 and 9.0 +/- 1.2 ml/min per kg, respectively. The data indicate that the cationic fluorescent xenobiotic, rhodamine, when conjugated to the bile salt analogue, greatly increased the biliary excretion of rhodamine and that cheno-lys acted as a carrier for hepatic uptake of rhodamine. Thus, an appropriate bile salt derivative may be used to target a drug to the liver. PMID- 1606174 TI - Inhibition of the accumulation of lipid droplets in macrophage J774 by bafilomycin B1 and destruxin E. AB - Two microbial metabolites, bafilomycin B1 and destruxin E, have been found to inhibit significantly the oxidized low density lipoprotein (LDL)-induced accumulation of lipid droplets at 3 nM and 0.5 microM, respectively, in macrophage J774. The incorporation of [14C]oleate into cholesteryl esters in the cells incubated with oxidized LDL was inhibited to the same extent by the two compounds. Both compounds had no effect on the cell surface binding at 4 degrees C and the internalization of oxidized 125I-LDL as well as on the activity of acyl CoA:cholesterol acyltransferase. However, when incubated with these compounds at 37 degrees C, receptors for oxidized LDL were partially trapped within the cell. In accordance with receptor accumulation, ATP-dependent acidification of endosomes and lysosomes was significantly inhibited by 50 nM bafilomycin B1 and 1 microM destruxin E, respectively. From these results it was concluded that the inhibition of ATP-dependent acidification of endosomes and lysosomes by bafilomycin B1 and destruxin E resulted in the reduction of oxidized LDL-induced synthesis of cholesteryl ester and thereby caused a reduced accumulation of lipid droplets in macrophage J774. PMID- 1606175 TI - Pathogenesis of lithocholate-induced intrahepatic cholestasis: role of glucuronidation and hydroxylation of lithocholate. AB - It has been shown that lithocholic glucuronide is more cholestatic than lithocholic acid (LCA), as well as its taurine and glycine conjugates. Furthermore, LCA hydroxylation is thought to be a major detoxifying mechanism. Therefore, the role of LCA glucuronidation and hydroxylation was investigated during the development of LCA-induced cholestasis and recovery from it. Male rats received a bolus intravenous injection of [14C]LCA (12 mumol/100 g body weight) and bile samples were collected every 30 min for 5 h. Bile flow (BF) was reduced immediately after LCA injection, dropping to 40% of basal BF at 60 min. It then started to increase, reaching normal bile flow values at 3.5 h. Morphologically, canalicular lesions were dominant at 60 min and virtually absent at 2 h. At 60 min (maximal cholestasis), 30% of the LCA injected was secreted in bile, 20% was found in plasma while the other 50% was recovered in the liver and distributed mainly in plasma membranes, microsomes and cytosol. At the end of the experiment (normal BF), 20% of the LCA injected was still in the liver but was present mainly in the cytosol. In bile, within 30 min after injection, 46% of the LCA secreted was lithocholic glucuronide, 24% was conjugated with taurine and glycine, and 21% was in the form of hydroxylated bile acids. During the recovery period, lithocholic glucuronide secretion decreased to 18-25%. Taurine and glycine conjugate secretion increased to a maximum of 43% at 60 min, after which it was reduced to 21-28%. In contrast, hydroxylated metabolites were elevated during the recovery periods, reaching a maximum (45%) at 120 min and remaining constant thereafter. These results suggest that: (i) LCA binding to plasma membranes and microsomes appeared to correlate with the development of cholestasis; (ii) LCA glucuronidation may initiate and/or contribute to LCA induced cholestasis; and (iii) hydroxylation predominates during recovery from cholestasis. PMID- 1606176 TI - Effects of sphingomyelin and phosphatidylcholine acyl chains on the clearance of triacylglycerol-rich lipoproteins from plasma. Studies with lipid emulsions in rats. AB - Series of lipid emulsions were prepared as physical models of lymph chylomicrons. The emulsion phospholipid was systematically varied with respect to sphingomyelin, in 0-100% mixtures with egg yolk phosphatidylcholine (EYPC). In other emulsions, the phospholipid was systematically varied with respect to dipalmitoylphosphatidylcholine (DPPC) in 0-100% mixtures with 1-palmitoyl-2 oleoylphosphatidylcholine (POPC). All emulsions contained unlabeled free cholesterol, radiolabeled triolein (TO) and radiolabeled cholesteryl oleate (CO). The emulsions were injected into conscious rats to measure the clearances of emulsion TO and CO and the capture of lipid radioactivity by selected organs. The emulsions containing EYPC or POPC were metabolized similarly to lymph chylomicrons, consistent with rapid lipoprotein lipase-mediated hydrolysis of emulsion TO followed by hepatic uptake of the CO in the triglyceride-depleted emulsion remnants. Emulsions stabilized with either 1-oleoyl-2-stearoyl- or 1 stearoyl-2-oleoylphosphatidylcholine (OSPC or SOPC) were metabolized similarly. Increasing amounts of sphingomyelin in EYPC emulsions progressively slowed the removal of TO and CO labels from plasma. With 50% sphingomyelin clearance was very slow, while emulsion clearance was negligible with 100% sphingomyelin. Emulsions containing 20% of DPPC in POPC were metabolized similarly to 100% POPC, but 40% or more of DPPC progressively slowed the removal from plasma of both TO and CO. With 100% DPPC clearance was characterized by a rapid initial removal of about 30% of the injected material, followed by a second phase when removal was negligible, suggesting lack of hydrolysis of triacylglycerols by lipoprotein lipase. Changes in the apolipoproteins associated with the emulsions probably mediated the observed changes in clearance. PMID- 1606178 TI - Increased cholesterol synthesis in Chinese hamster ovary cells deficient in peroxisomes. AB - In a previous study we have shown that Chinese hamster ovary (CHO) cells deficient in intact peroxisomes, lack the nonspecific lipid transfer protein (nsL TP; sterol carrier protein 2) (van Heusden, G.P.H., Bos, K., Raetz, C.R.H. and Wirtz, K.W.A. (1990) J. Biol. Chem. 265, 4105-4110). The consequences of the absence of peroxisomes and of nsL-TP on intracellular cholesterol metabolism have been investigated in two peroxisome-deficient CHO cell lines (CHO-82 and CHO-78). Compared with wild-type cells (CHO-K1), the incorporation of [3H]acetate into cholesterol was 3-fold higher in the CHO-82 cells and 2-fold higher in the CHO-78 cells. In agreement with an increased synthesis of cholesterol, a 2-3-fold higher 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was measured in both mutant cell lines. On the other hand, addition of low density lipoprotein (LDL), mevalonate (30 mM) or 25-hydroxycholesterol (2 micrograms/ml) to cells grown in lipoprotein-deficient serum, demonstrated that in both mutant cell lines the down regulation of HMG-CoA reductase and of cholesterol synthesis were comparable to that in wild-type cells. These results strongly suggest that, in addition to down regulation by LDL-derived cholesterol, mevalonate and 25-hydroxycholesterol, HMG CoA reductase activity is under control of peroxisomes and/or nsL-TP. PMID- 1606177 TI - High density lipoprotein mediates selective reduction in cholesteryl esters from macrophage foam cells. AB - To elucidate an anti-atherogenic nature of high density lipoprotein (HDL) at cellular level, its in vitro effect on macrophage foam cells was examined. Rat peritoneal macrophages were converted to foam cells by incubation with [3H]cholesterol-labeled acetylated LDL. HDL addition to these foam cells resulted in a reduction in cellular radioactive cholesteryl esters (CE) as well as its CE mass. The radioactive free cholesterol (FC) was similarly reduced with time, whereas its FC mass level was unaltered. Other lipoproteins such as very low density lipoprotein and low density lipoprotein also reduced the radioactive FC. However, their CE-reducing capacity was negligibly weak. These results suggest that (i) CE reduction is selective to HDL, (ii) FC transfer from plasma membrane to lipoprotein (cholesterol efflux) expressed by reduction in radioactive FC is not selective to HDL but occurs to other lipoproteins, (iii) the CE-reducing capacity of HDL became weaker when cellular binding of HDL was reduced by chemical modification with tetranitromethane or a chemical cross-linker, dithiobis-succinimidylpropionate, suggesting an importance of the specific binding in the HDL-mediated CE reduction. These in vitro results gave an experimental support to a definite role of HDL as an anti-atherogenic lipoprotein in vivo. PMID- 1606179 TI - Solubilization and partial purification of constituents of acyl-CoA elongase from Lunaria annua. AB - All the constituent enzymes of acyl-CoA elongase, i.e., beta-ketoacyl-CoA synthase, beta-ketoacyl-CoA reductase, beta-hydroxyacyl-CoA dehydrase and trans-2 enoyl-CoA reductase, have been solubilized from a 15,000 x g particulate fraction from developing seeds of honesty (Lunaria annua) using Triton X-100. All these activities were retained upon subsequent precipitation of the solubilized protein with polyethylene glycol and resuspension of the precipitate followed by ion exchange chromatography of the resulting protein on DEAE-cellulose. A 4.2-fold enrichment of the acyl-CoA elongase was thus obtained. Further chromatography of the DEAE fraction containing all the constituents of acyl-CoA elongase on Ultrogel yielded a major protein fraction exhibiting the activities of beta ketoacyl-CoA synthase and beta-ketoacyl-CoA reductase only. Almost 30-fold purification of the beta-ketoacyl-CoA synthase was thus achieved. The beta ketoacyl-CoA synthase was inhibited only at high concentrations of cerulenin, but at very low concentrations of iodoacetamide. Inhibition could be reduced by preincubation with thioesters, indicating that an enzyme thioester intermediate is involved in the condensation reaction of the acyl-CoA elongation. PMID- 1606180 TI - Competitive inhibition of lipolytic enzymes. VIII: Inhibitor-induced aggregation of porcine pancreatic phospholipase A2. AB - Several 2-acylaminophospholipid analogues have been demonstrated to behave as potent competitive inhibitors of porcine pancreatic phospholipase A2 (De Haas, G.H., Dijkman, R., Ransac, S. and Verger, R. (1990) Biochim. Biophys. Acta 1046, 249-257). Their inhibitory power appeared to be strictly controlled by the stereoconfiguration around the chiral C-2 atom and effective inhibition of the enzyme was observed only when incorporated into a micellar substrate-water interface. In the present study various direct binding techniques were applied to investigate the interaction of the enzyme with pure micelles of the stereoisomeric forms of 2-tetradecyl-amino-hexanol-1-phosphocholine (R-C14-PN and S-C14-PN). Upon equilibrium gel filtration of the enzyme (monomeric molecular mass = 14 kDa) on calibrated Superdex columns running in micellar solutions of R C14-PN, the phospholipase eluted as a lipid-protein complex of 74 kDa. Under identical conditions, micellar solutions of S-C14-PN did not give rise to high molecular mass aggregates and the enzyme eluted at its normal 14 kDa position. Light scattering experiments, ultrasedimentation and time-resolved fluorescence spectroscopy studies confirmed the formation of a high-molecular mass aggregate between enzyme and R-C14-PN micelles. The ultimate complex was shown to consist of four protein and about ten inhibitor molecules. Using time-resolved fluorescence spectroscopy the interaction was studied between the active site of phospholipase A2 and R-C14-PN molecules, both incorporated in an inert lipid matrix. PMID- 1606181 TI - A gas chromatographic/mass spectrometric assay for prenylamine suitable for pharmacokinetic studies of the racemate and the enantiomers. AB - A sensitive assay for prenylamine and dideuteroprenylamine (racemic or pseudo racemate) has been developed and used in human pharmacokinetic studies. Plasma levels of prenylamine could be measured up to 50 h after a single oral therapeutic dose. The extracted drug was derivatized with pentafluoropropionic anhydride in acetonitrile. The dried samples were reconstituted in decane; an aliquot was injected into a fused-silica capillary in a cooled on-column injector. The base peaks in the electron impact mass spectra of the compounds- derived by loss of a benzyl radical--at m/z 384, 386 and 390 were measured for prenylamine, (D2)-prenylamine and the internal standard hexahydroprenylamine, respectively. The sensitivity of this assay--limit of detection 0.2 ng ml-1 plasma with a signal-to-noise ratio of 5:1--allowed measurement of the kinetics of the racemate and of both stereoisomers for the first time. In man, the (+) isomer was eliminated considerably faster than the (-)-prenylamine; the area under the plasma concentration time curve (AUC) of the (+)-isomer was only about 1/4 of the AUC of (-)-prenylamine. PMID- 1606182 TI - Mass isotopomer pattern and precursor-product relationship. AB - The synthesis of a homonucleus polymer from its labeled precursor will lead to the formation of molecules with different masses. The distribution of these mass isotopomers is strictly a function of the enrichment of the 13C-labeled precursor, and can thus be used for the determination of the precursor enrichment and product dilution in the de novo synthesis of the polymer. We present here a study of the isotopomer pattern of a polymer of acetate in the form of glucose pentaacetate synthesized from 13C-enriched acetic anhydride. The molecular ion contains four acetyl units. Its synthesis is analogous to that of octanoic acid from acetyl coenzyme A. The process of obtaining the mass isotopomer distribution in the tetraacetyl moiety from the ion cluster of m/z 331 of glucose pentaacetate is illustrated. After correcting for the contribution of 13C natural abundance, the plot of the ratio of mass isotopomers (m4/m2) against the observed enrichment of the tetraacetate moiety yielded a straight line with a slope of 1.45. The ratio was not altered by dilution with pre-existing unenriched product, as predicted. The slope of the observed linear relationship agreed with the general formula (N-(j-1))/j for the ratio of any two consecutive mass isotopomers (mj/mj 1). Theoretical and practical aspects of determining precursor enrichment from isotopomer pattern in polymers are discussed. PMID- 1606183 TI - Determination of L-365,260, a new cholecystokinin receptor (CCK-B) antagonist, in plasma by liquid chromatography/atmospheric pressure chemical ionization mass spectrometry. AB - L-365,260 is a novel cholecystokinin receptor antagonist. A sensitive and specific liquid chromatographic/mass spectrometric assay has been developed for the determination of the drug in plasma using the CD3-labeled species as the internal standard. Plasma extracts were separated on a 3 cm C18 reverse-phase high-performance liquid chromatography column. The column eluate passed, by means of a heated nebulizer interface, into a corona discharge atmospheric chemical ionization source. The mass spectrometer was operated in the positive ion tandem mass spectrometric mode. The method has sufficient sensitivity, specificity, precision, accuracy and selectivity for the determination of drug concentrations in clinical samples. The chromatographic run time is less than 2 min. PMID- 1606184 TI - Gas chromatographic/mass spectrometric analysis of high-performance liquid chromatographic fractions reflecting arachidonic acid metabolism in mouse peritoneal macrophages. AB - Mouse peritoneal macrophages are used as a model for studies undertaken around the oxidative metabolism of arachidonic acid elicited by xenobiotics (N phenyllinoleamide, related to the toxic oil syndrome, has been used as an example). A high-performance liquid chromatographic method for cyclo- and lipoxygenase metabolite fractionation has been developed. Gas chromatographic/mass spectrometric analysis of the high-performance liquid chromatographic fractions thus obtained show that the major products detected in the incubates correspond to three principal structures: monohydroxy acids (12 hydroxyeicosatetraenoic acid being the major component), epoxyhydroxy acids and trihydroxy acids. Other minor compounds such as 12-hydroxyheptadecatrienoic acid, various dihydroxy acids and prostaglandins were also detected. Cells pre-exposed to N-phenyllinoleamide show selectively enhanced levels of 6-keto prostaglandin F1 alpha, as measured by both gas chromatography/mass spectrometry and radioimmunoassay of the corresponding high-performance liquid chromatographic fraction. PMID- 1606185 TI - Endogenous lithium determination in blood plasma and urine by isotope dilution mass spectrometry and preliminary isolation of lithium fraction using paper chromatography. AB - A version of isotope dilution mass spectrometric technique elaborated for measuring endogenous lithium concentrations in human blood plasma and urine (10( 7) M region) and applicable in clinical practice is described. A tracer solution of lithium (LiCl) enriched in 6Li (with abundances 6Li 92%, 7Li 8%) is added to a certain volume of human plasma (0.2-0.4 ml) or urine (0.05-0.1 ml) and dried under an infrared lamp. Thereupon a soluble part extracted from dried plasma with the aid of 0.1 N HCl is dried as well. Dry extracts from plasma and dried samples of urine are processed by 30% H2O2 and subsequently subjected to paper chromatography (with ethanol as a solvent). Such processing of samples is simple and short (about an hour, 3 min of chromatographic process inclusive), achieving a good separation from organic matrix and interfering macroelements. Contamination of sample in processing is about 2-5 pmol; routine control of contamination and account of their influence are accomplished by measuring two different volumes of each sample. Measurements are made with high precision: cyclic repeated scanning of 7Li and 6Li peaks have a standard deviation of 7Li/6Li ratio no more than 0.7%. The method described was used to determine endogenous lithium clearance of hypertensive patients and patients with transplanted kidney. PMID- 1606186 TI - Some proline substituent effects in the tandem mass spectrum of protonated pentaalanine. AB - Tandem mass spectral effects of the replacement of alanine by proline in pentaalanine were studied. The principal difference when residue 3 or 4 is proline is the great enhancement of the y3 or y2 ion, respectively. This is precisely the principal difference which thermochemical arguments predict, since a y-type ion with N-terminal proline is estimated to be 32 kJ mol-1 more stable than with N-terminal alanine. When this proline effect and the effect of neutral diketopiperazine loss occur simultaneously, the y-type ion is not observed, as predicted from the additivity of substituent effects by the kinetic approach. No interpretation is offered for observations of b-type ion intensities, since the pattern is not obvious to us. PMID- 1606187 TI - Determination of endothelium-derived nitrite/nitrate by gas chromatography/tandem mass spectrometry using (15N)NaNO2 as internal standard. AB - A sensitive gas chromatographic/tandem mass spectrometric method for the determination of nitrite and nitrate in endothelial cell column perfusates was developed. Nitrite/nitrate were converted in the presence of the internal standard (15N)NaNO2 to the corresponding 1-nitro-2,4,6-trimethoxybenzene (NTMB) derivatives which were subsequently analysed by gas chromatography/tandem mass spectrometry, monitoring m/z = 46 and m/z = 47, respectively. The good reproducibility, the wide linear range of the calibration curve from 25 ng ml-1 to 2500 ng ml-1 nitrite and the low detection limit of 200 pg NTMB allowed a sensitive and accurate quantification of nitrite/nitrate in perfusates of endothelial cell columns. Bradykinin had a stimulating effect on human and bovine endothelial cells and led to a threefold increase of nitrite/nitrate in endothelial cell column perfusates compared to those of unstimulated cells. PMID- 1606188 TI - Simultaneous quantitation of arecoline, acetylcholine, and choline in tissue using gas chromatography/electron impact mass spectrometry. AB - A capillary gas chromatography/mass spectrometry (GC/MS) assay for the simultaneous quantitation of arecoline (ARE), acetylcholine (ACh), and choline (Ch) in biological tissue has been developed. The method utilizes hexadeuterated ARE and nonadeuterated ACh and Ch as internal standards. The compounds were ion pair extracted from tissue using sodium tetraphenylboron in 3-heptanone. GC/MS analysis was achieved using capillary GC and electron impact mass spectrometry. Quantitation was accomplished using selected ion monitoring at m/z 140 and 146 for non-deuterated and deuterated arecoline respectively, and m/z 58 and 64 for non-deuterated and deuterated ACh and Ch respectively. The method easily detected 25 pmol of all three compounds taken through the assay, and was linear through 50 nmol. PMID- 1606189 TI - Factors predicting suicide in psychotic patients. AB - Death rate and causes of death during a mean period of 5.8 years were investigated in 250 male inpatients with psychotic disorders (DSM-III). Fifty patients died during the observation period. Suicide was confirmed in 11 of these patients and could not be excluded in 7 cases, where the cause of death was reported as uncertain. Clinical and neurobiological characteristics (DST-non suppression, CSF proteins, and monoamine metabolites) were compared in patients who committed suicide and non-suicide patients of the same age, with or without suicidal behaviour. A highly increased mortality rate was seen among the patients and the rate of suicide was more than 20 times higher than that expected in a normal population of the same age. The estimated annual incidence of suicide was 2.5%, 1.3%, 1.0% and 0.4% for patients with bipolar disorder, paranoid psychosis, major depression and schizophrenic disorder, respectively. The following factors were significantly positively correlated with completed suicide: depressive mood, elated mood, paranoid ideas, and paternal age. All suicides had previously shown suicidal behaviour and the suicide occurred during or shortly after a period of hospitalisation. No correlations were found with age at onset of illness, duration of illness, substance abuse or neurobiological parameters. PMID- 1606190 TI - Postural imbalance: an early sign in HIV-1 infected patients. AB - We have recorded postural performance in 50 HIV-infected patients in different stages of the disease (Walter Reed (WR) stages I-VI) by means of a force measuring platform. The results were compared with 50 age-matched controls. A significant instability was particularly evident when standing on an unstable foot support. In patients standing with "eyes closed", postural sway was significantly higher in every patient group (WR I-II: P less than 0.02, WR III-V: P less than 0.001, WR VI: P less than 0.001). Patients in stage WR I-II showed no relevant neurological abnormalities. In agreement with other neurophysiological data in the literature we suggest that postural imbalance could be an early sign of central nervous system penetration of HIV. No correlation with electromyographic or cerebrospinal fluid findings could be found. PMID- 1606191 TI - Lifetime and 6-month prevalence of abuse and dependence of alcohol in the Munich Follow-up Study. AB - This paper reports lifetime and 6-month prevalence rates of alcohol abuse and dependence in West Germany. Assessment instruments are a modified German version of the Diagnostic Interview Schedule (DIS), a fully standardized interview for the assessment of selected DSM-III diagnoses and the Munich Alcoholism Test (MALT). According to the DIS/DSM-III criteria, 13.0% of the adult general population (aged 25-64 years) were found to fulfill the lifetime criteria for alcohol abuse, alcohol dependence, or both; however, only 1.3% of all men and 0.9% of the women interviewed received a current DSM-III diagnosis of alcohol abuse or dependence. There was good consensus between current DSM-III diagnoses with current clinical ICD-diagnoses, but poor concordance with lifetime diagnoses. Symptoms of alcoholism, onset and severity, comorbidity with other DIS/DSM-III disorders as well as some selected risk factors are reported. The results are primarily compared with the results of the US-Epidemiological Catchment Area Program (ECA). PMID- 1606192 TI - Magnetic resonance in patients with affective illness. AB - Magnetic resonance imaging is presently being utilized to understand the neuropathology of affective disorders. Present research has demonstrated brain changes in affective disorders that correlate with neuroendocrine findings and are similar to changes noted in normal aging. PMID- 1606193 TI - The Zurich Study. XIII. Recurrent brief anxiety. AB - In the epidemiological Zurich cohort study a syndrome of 'Recurrent Brief Anxiety' (RBA) was identified and operationalized. It had a 1-year prevalence rate of 2.7, males seemed to prevail slightly. RBA was highly associated with 'Recurrent Brief Depression' (RBD) and panic, and to a minor extent with agoraphobia and dysthymia. The family history was positive for depression and anxiety (panic, generalized anxiety disorder). In studies of panic, one should look for the frequently associated syndromes of RBA and RBD. PMID- 1606194 TI - The Zurich Study. XIV. Epidemiology of seasonal depression. AB - In a longitudinal cohort study of young adults from the Canton of Zurich in Switzerland (Zurich Study), seasonal patterns of several psychiatric and psychosomatic syndromes were investigated in two interviews over a period of three years. At an age of 27-28 years, 23% of the depressives, 15% of the neurasthenic subjects, and 14% of the subjects with backache reported an increased susceptibility in autumn and/or winter. With respect to the course we found that 10.4% of the subjects of the longitudinal sample (n = 417) suffered from seasonal depression (including individuals with subsyndromal seasonal difficulties) over two consecutive years. Specific symptoms, such as hypersomnia, increase of appetite or weight gain, were not found to be consistently associated with seasonal depression. A comparison of actual and retrospective reports on seasonal depression resulted in a very low reliability. In view of these results the seasonal subtype of depression should be diagnosed with caution, except when the diagnosis is based on longitudinal observations and/or external sources of information (e.g. family members, partner). PMID- 1606195 TI - Failed and short seizures associated with prior electroconvulsive therapy. AB - Electroconvulsive therapy (ECT) has not been associated with many long-lasting effects that are associated with the treatments itself. The impact of having prior ECT to determine if the increased seizure threshold that is noticed during the treatment course is long-lasting was studied. If so, more failed and short seizures should occur among those patients who have had prior electroconvulsive treatments. A review of the treatments of 114 males and 220 females indicated a strong association of prior ECT with failed as well as short seizures for men but not for women. PMID- 1606196 TI - Falling spells associated with antidepressant drug treatment. AB - Six patients experienced falling spells concurrent with the intake of antidepressant drugs in high doses or in moderate doses combined with other psychotropic drugs. The close temporal correlation between drug ingestion and the falling spells and their immediate termination after reduction or discontinuation of medication suggests that these drugs caused the falls. Further factors predisposing to the falling spells remain to be defined. PMID- 1606198 TI - Risk of suicide by psychiatric diagnosis in Stockholm County. A longitudinal study of 80,970 psychiatric inpatients. AB - The risk of suicide associated with different psychiatric diagnoses was estimated in 80,970 inpatients in Stockholm County (population 1.6 million). All patients discharged with at least one psychiatric diagnosis between 1973 and 1986 were followed by linkage with the cause-of-death registry through 1987. There were 1,115 definite suicides and 467 undetermined suicides among these during the 15 year follow-up. When 12 diagnostic categories were entered in a proportional hazards model, the highest relative risk (RR) of definite suicide, controlling for sex and age, was noted for affective disorders (RR 2.82), followed by unspecified psychoses (RR 2.69), paranoid psychoses (RR 2.60), addiction to prescription drugs (RR 2.38), neuroses and reactive psychoses (RR 1.96), and schizophrenia (RR 1.64). Alcoholism, personality disorders, organic psychoses, and street drug addiction did not have significantly increased risks of suicide. Male sex increased the risk for definite suicide by 1.56, while the risk was somewhat higher among the young. Having more than one diagnosis increased the relative risk by 1.42. When undetermined suicides were included in the analysis, to alcoholism and street drug abuse were attributed significantly increased risks of suicide, probably owing to the greater difficulty of verifying such cases. We conclude that several psychiatric disorders were conductive to suicide, but that the risk did not vary much with the type of diagnosis. Further studies of confounders are needed, such as the reasons for being admitted to inpatient care, and the impact of somatic and psychiatric comorbidity. PMID- 1606197 TI - Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. AB - Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus. We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis. Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex. This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it. PMID- 1606199 TI - Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 1. Euthymic rats. AB - We performed a comparative evaluation of the immune status, focused on the T-cell system, of euthymic rat strains in which the nude mutation had been introduced. From 10 institutes, we sampled 12 groups of euthymic rats at ages of 1 1/2-2 months and 1/2 year. We analyzed weight of body, spleen and thymus; antibody response and delayed-type hypersensitivity response to ovalbumin immunization; and (immuno)histopathology of spleen, lymph nodes, and lymphoid tissue along the gastrointestinal tract. In the spleen morphometric analysis was done of the periarteriolar lymphocyte sheath (using the antibody R73 recognizing the alpha beta-T-cell receptor) and of the red pulp (using the antibody ED2 recognizing red pulp macrophages). For almost all parameters tested, statistically significant differences between the groups (origin of the animals) were observed. A cluster analysis on the basis of body weight, spleen weight, and morphometric data of spleen did not yield clusters with a different composition among animals from individual groups. Based on the antibody response to ovalbumin, clustering revealed groups of "fast-and-high", "slow-and-low", and "intermediate" responders. The various groups differed in location within these clusters, i.e. the speed and extent of the immune response depends on the background euthymic strain. Considering the microbiological status assessed by serology, a variation was found both in post-infection state at entrance in the study, and in primo infection associated with a rise in antibody concentrations during the study. These states showed no negative effect on anti-ovalbumin reactivity. Rather, the response in primo-infection to Rat Corona Virus, Sendai Virus, and Pneumonia Virus of Mice was the highest in animals clustered as "fast-and high" responders to ovalbumin. PMID- 1606200 TI - Changes in rat leukocyte populations in peripheral blood, spleen, lymph nodes, and synovia during Erysipelas bacteria-induced polyarthritis. AB - Kinetics of leukocyte subsets were followed for several weeks in rats suffering from polyarthritis induced by experimental infection with erysipelas bacteria (Erysipelothrix rhusiopathiae, serovar 2, strain T28). A marked leukocytosis was found in peripheral blood, and, with some delay, in the synovia and draining lymph nodes of affected joints. In the lymphoid organs tested considerable blast formation of lymphoid cells with a paucity of polymorphonuclear granulocytes was found, while the latter represented the majority of leukocytes in acutely inflamed joints. Cells isolated from spleen showed only moderate and transient alterations in proportions of subpopulations during the first week after inoculation of erysipelas bacteria. In contrast, cells isolated from synovia of inflamed joints and draining lymph nodes displayed more intense and longer lasting alterations: In arthritic animals, the proportion of MHC class II positive lymphocytes generally increased and remained elevated at least during the first three weeks of the disease. Spontaneous release of IL-2 from cells isolated up to 20 days post induction of the arthritis indicated a considerable activation of lymphocytes in vivo. Interestingly, with exception of synovia, the relative amount of T-lymphocytes including their major CD4+ and minor CD8+ subsets showed little alteration during the course of the disease. Much more pronounced were the rapidly and the extent the membrane Ig-positive B-lymphocytes increased in the synovia as well as in the lymph nodes. Thus, B-lymphocytes may be of particular relevance for elucidating pathomechanisms of erysipelas polyarthritis. PMID- 1606201 TI - Comparative evaluation of the immune status of congenitally athymic and euthymic rat strains bred and maintained at different institutes: 2. Athymic rats. AB - We performed a comparative evaluation of the immune status, focused on the T-cell system, in congenitally athymic rat strains. From 11 institutes around the world, we sampled 15 groups of animals at ages of 1 1/2-2 months and 1/2 year. The analysis included weight of body and spleen; antibody response and delayed-type hypersensitivity response after immunization with ovalbumin; and (immuno)histology of spleen, lymph nodes and lymphoid tissue along the gastrointestinal tract. Morphometric analysis was done for alpha beta-T-cell receptor-bearing cells in spleen tissue as a measure of the periarteriolar lymphocyte sheath; it was also done for splenic red pulp using the antibody ED2 recognizing red pulp macrophages. For almost all variables analyzed, statistically significant differences between the groups were observed. The extent of alpha beta-T-cell receptor-bearing cells in the spleen increased with age. The functioning of these cells in immunological responses can be questioned, because an immune response to ovalbumin was invariably absent. But secondary follicles with germinal centers, reflecting T-cell-dependent B-cell reactivity, were observed in lymph nodes and Peyer's patches (up to 40% and 75%, respectively, depending on the group), with a higher prevalence in older animals. A cluster analysis on the basis of body and spleen weight and composition of spleen compartments did not yield clusters with a different profile in regard to the animals' group of origin. The data presented are useful when comparing studies performed with various athymic rat strains at different institutes. PMID- 1606202 TI - Safety in the workplace: our greatest challenge. PMID- 1606203 TI - What issues and procedures should concern you as a CRNA manager when a CRNA employee has been diagnosed as HIV positive? AB - Today's manager is faced with a multitude of issues regarding the HIV-infected health-care provider. A well-planned and organized response to such a situation can best meet both employer and provider needs. The manager should possess the knowledge to both respond appropriately and utilize the necessary resources in accommodating the HIV-infected employee. Recommendations are made to consider should this situation present. PMID- 1606204 TI - Incidence of arterial oxygen desaturation in cardiac patients premedicated with intramuscular scopolamine and morphine. AB - The effect of a standard preoperative medication combination, morphine and scopolamine, on arterial oxyhemoglobin saturation was measured continuously in 29 patients scheduled for elective coronary artery bypass grafting procedures. On the morning of operation, both before and after administration of preoperative medication, each patient was monitored continuously with a pulse oximeter (SpO2). Patients received 0.05 to 0.11 mg/kg of morphine (mean = 6.0 +/- 2.1 mg) intramuscularly (IM) and 0.2 to 0.4 mg of scopolamine (mean = 0.30 +/- 0.07 mg) IM. The mean arterial blood oxyhemoglobin saturation decreased from 92.0 +/- 1.8% before preoperative medication to 89.0 +/- 3.8% (P greater than .001) after preoperative medication. Forty-five percent of the patients had SpO2 less than 90% for at least 2 minutes, and 21% below 85%. In conclusion, significant arterial oxyhemoglobin desaturation occurred in this group of cardiac surgical patients after preoperative medication with morphine and scopolamine. Prophylactic administration of oxygen with preoperative medication might reduce the incidence of hypoxemia in this group of patients at risk for myocardial ischemia. PMID- 1606205 TI - Antitrust issues for the nurse anesthetist: areas of concern. AB - This article is the second of a two-part article on antitrust issues as applicable to certified registered nurse anesthetist (CRNAs). The first part, presented in the March 1992 issue, provided an overview of antitrust law and discussed issues related to establishing jurisdiction under federal law. The second part, presented in this issue, focuses on specific antitrust areas of concern to the CRNA, including staff privileges, peer review, price fixing, and insurance. Specific practical recommendations for dealing with antitrust situations are offered. PMID- 1606206 TI - Clinical hypnosis in the practice of anesthesia. AB - Hypnosis has been utilized for at least several hundred years, but the societal view of hypnosis has ranged from raving to ridicule. The advances of hypnosis as a scientific endeavor have occurred within the last two centuries, but many myths and misunderstandings remain about the nature of hypnosis and its effects on the subject. Hypnosis is being recognized as having many medical applications. Important applications for the anesthetist include hypnoanesthesia and hypnoanalgesia, which are found to have some advantages in specific types of patients that present for surgery. PMID- 1606207 TI - Understanding the Institutional Review Board. PMID- 1606208 TI - The inappropriateness of psycho-social models of risk behaviour for understanding HIV-related risk practices among Glasgow male prostitutes. AB - Much the most common models of HIV-related risk behaviour are those psychosocial models derived from studies of health behaviour and tested on large interview samples of American gay men. These models were not appropriate for understanding risk behaviour among 32 Glasgow male prostitutes. Whereas psycho-social models conceive of risk behaviour as volitional and individualistic, ethnographic data indicate that the male prostitutes' risk practices were constrained and emergent from the immediate circumstances of the sexual encounter. Unsafe sex was associated with client control. Safer sex was associated with countervailing prostitute strategies of influence. These data confirm the utility of self empowerment approaches to health education. PMID- 1606209 TI - Differences across sexual orientation on HIV risk behaviours in injecting drug users. AB - Injecting drug users (IDUs) play a disproportionate role in the spread of HIV given their injecting and sexual contacts, and thereby act as conduits between these risk groups. We investigated differences in risk behaviour and HIV seroprevalence in a Sydney sample of 1,245 IDUs. Significant differences were observed across sexual orientation in HIV serostatus for males, with homosexual men having the highest HIV seroprevalence rate (35%), bisexual men intermediate (12%) and heterosexual men lowest (3%). Sexual HIV risk behaviours were lowest for homosexual men, intermediate for bisexual men, and highest for heterosexual men in the case of condom use: however, for numbers of partners, seroprevalence, and anal sex the trends were reversed. There were no differences across sexual orientation for either sex for injecting drug risk behaviours. Both male and female respondents reported having more than 50% of sexual contacts while under the influence of drugs. This study suggests that risk reduction in the sexual domain has not generalized to the injecting risk domain regardless of sexual orientation, and demonstrates that sexual risk behaviours in IDUs are lowest in homosexual, intermediate in bisexual, and highest in heterosexual IDU men. PMID- 1606210 TI - Partners of men with HIV infection and haemophilia: controlled investigation of factors associated with psychological morbidity. AB - The study was concerned with determining the prevalence of psychosocial problems in partners of men with haemophilia and HIV infection, and with identifying factors associated with psychological morbidity. Partners of 17 HIV positive and partners of 19 HIV negative men with haemophilia were assessed in a cross sectional controlled investigation. Outcome measures included current psychological status and psychiatric history; coping and health beliefs; and social and sexual functioning. Partners of HIV positive men with haemophilia, the majority of whom were asymptomatic, were not found to suffer more psychological difficulties than the partners of HIV negative men with haemophilia. However, partners of haemophiliacs regardless of HIV status suffer from higher levels of psychological distress than comparable women in the community, and those with past psychiatric history and current social difficulties are particularly at risk. The sexual relationships of couples with HIV positive men were more adversely affected than those of HIV negative couples. PMID- 1606211 TI - Testing for HIV in the antenatal clinic: the views of midwives. AB - Self administered questionnaires were given to 34 midwives, who regularly counsel parturient women about the HIV antibody test, to investigate their attitudes to the test being offered in the antenatal clinic. Most of the midwives felt that testing should not be compulsory and that the test should be offered to all pregnant women who ask for it, not only those in recognized risk groups. Most also felt that women should be told the results of the test and that it should not be the midwives aim to increase the number of women having the test. Most felt that all midwives should counsel about the test but would like health advisers, GPs and obstetricians to be involved also. They also felt that they did not have sufficient knowledge in some areas to counsel particularly with regard to the practical and psychological implications of being HIV positive. This has implications in terms of the provision of adequate pre-test counselling for all pregnant women as an improvement in counselling services requires an allocation of finances, e.g. for training of midwives, which may be seen as unnecessary in areas of low seroprevalence. Further discussion and debate of these issues is required. PMID- 1606212 TI - The sexual behaviour of bisexual men in relation to HIV transmission. AB - Relatively little is known about the behaviour of bisexual men which may help in assessing their role in HIV transmission. A sample of 60 behaviourally bisexual men were asked about their sexual behaviour with male and female partners and their perceptions of risk of HIV infection. Only a minority of men engaged in unprotected anal sex with their male partners while two thirds had unprotected vaginal sex with their female partners. This asymmetrical pattern of sexual behaviour reflects a differential perception of risk of HIV infection with male and female partners. A quarter of the men had unprotected penetrative sex with both male and female partners in the previous year. The pattern of risk behaviour varied amongst men living in gay, heterosexual or bisexual contexts. PMID- 1606213 TI - A randomized trial of group interventions for hospital staff caring for persons with AIDS. AB - The purpose of this study was to develop an educational package for health care providers. Findings from a survey conducted by investigators were used to direct intervention content. All subjects received a 1 hour educational package. Since this type of intervention was not expected to be sufficient to modify attitudes and concerns, 75% of the subjects received an additional 1 hour group discussion intervention (n = 118). In a subgroup of those receiving group interventions, the discussion was preceded by the presence of a person with AIDS (PWA) (in person or on video) discussing his personal experience with the illness and health care workers. It was demonstrated that in order to modify change attitudes, concerns, and affective response, groups were necessary. Furthermore, fear of risk of contagion and homophobia required the presence of a PWA (in person or on video) in order for change to occur. PMID- 1606215 TI - Community-based health services for people with HIV/AIDS: a review from a health service perspective. AB - Health services for people with HIV/AIDS have been mainly hospital based, but it is now recognized that much care can be provided outside hospitals. There are well documented problems in delivering care in the community to other client groups such as the elderly and the mentally ill, but there are particular difficulties with HIV/AIDS care. These stem in part from the clinical demands of AIDS-related illnesses, but also from the stigma associated with the disease. This review looks at three key areas of relevance to those planning community based health services for people with HIV/AIDS. These are: the need for collaboration between the statutory and voluntary sectors; the need for co ordination between providers at the point of service delivery; and whether care should be provided by generic or specialist providers. While certain universal principles apply, and are necessary to ensure a good standard of care, patterns of service delivery will inevitably vary according both to the local prevalence rates and the existing service infrastructure. There is more than one good model of care; all models must be flexible enough to deal with needs on an individual basis. PMID- 1606214 TI - Estimating sexual behaviour parameters in the light of AIDS: a review of recent UK studies of young people. AB - This paper reviews UK surveys of the sexual behaviour of young people since the advent of AIDS. The studies, which are restricted to those whose samples were intended to be representative of the general population, reveal broadly similar estimates of key sexual behaviours (numbers with sexual experience, numbers of partners, frequency of intercourse, condom use and anal penetration). In spite of these similarities and the usefulness of such information for estimating the potential rate of transmission of HIV a number of methodological issues continue to afflict this kind of research. The paper calls for standardized question formats and a centralized body to monitor changes in these parameters of sexual behaviour. PMID- 1606216 TI - Training, workload and stress among HIV counsellors. PMID- 1606217 TI - World Health Organization Global AIDS Statistics. PMID- 1606218 TI - [Mosaic genes and moderate sensitivity to penicillin in Neisseria meningitidis]. PMID- 1606219 TI - [Comparison of Yersinia enterocolitica strains isolated from swine and humans in Guipuzcoa]. AB - Yersinia enterocolitica biotype 4, serotype 3 is a pathogenic bacteria for men. Its most likely reservoir are pigs. We have compared 48 Y. enterocolitica serotype 0:3 strains isolated from pig's tonsils samples as well as porcine derived food with 301 Y. enterocolitica serotype 0:3 isolate from human stool's samples. All strains are positive for virulence tests. Yersinia enterocolitica serotype 0:3, biotype 4, phage-type VIII was nearly the only single pathogenic strain isolated from both origins in our county. Human and porcine strains showed a similar percentage of chloramphenicol and cotrimoxazol resistance. This pattern of resistance is not common among Y. enterocolitica strains isolated outside of our geographic area. The nearly identical patterns of human and porcine strains, as well as the high frequency of isolation from pig's tonsils (49.5%) and uncooked meal (12.9%) confirm the hypothesis that pigs are the most likely reservoir for human infections in our county. PMID- 1606220 TI - [Evaluation of two commercial kits for detection of Helicobacter pylori specific antibodies in patients undergoing gastroscopy. A seroprevalence study in an asymptomatic population]. AB - BACKGROUND: We evaluate two different commercially available kits for detecting specific antibodies against Helicobacter pylori in a group of 48 patients with gastrointestinal symptoms that underwent an endoscopic procedure. We also study the seroprevalence of anti-H. pylori antibodies in asimptomatic individuals from our area. METHODS: Microbiologic and pathologic studies were performed in 48 gastric biopsies, in relation with antibodies detection using ELISA (Pylori stat test, Whittaker) and latex particles agglutination (Pyloriset, Orion). We also used ELISA tests for determining the seroprevalence of H. pylori antibodies in 139 asimptomatic individuals. RESULTS: Ninety-four percent of patients with peptic ulcer disease and 81% of patients without peptic ulcer disease but complaining of dyspepsia were infected by H. pylori. None of the patients with normal gastric mucosae was found to be infected. Sensitivity and specificity of ELISA test were 100% and 73%. Latex test sensitivity and specificity were 46% and 82%. The seroprevalence of antibodies among healthy individuals in our area increases with age (19% among children under 9 years of age) and reaches a peak at 40-49 years of age (84%), with a mean value of 60% in all ages' groups. CONCLUSIONS: There is a high correlation between Helicobacter pylori infection and gastric mucosa alterations. The ELISA test is best correlated with other laboratory data used for defining infection. The seroprevalence of H. pylori antibodies is also high, and therefore we recommend that the use of serologic diagnostic test must be highly selective. PMID- 1606221 TI - [Standardized immunoenzyme analysis for detection of IgG antibodies against Candida albicans in systemic candidiasis]. AB - We evaluate the usefulness of an ELISA test for detecting IgG antibodies against Candida albicans somatic and metabolic antigens. We studied 68 sera samples of patients with disseminated candidosis due to C. albicans in most of the cases. We used an ELISA test standardized with a monoclonal anti-IgG conjugate marked with peroxidase and soluble C. albicans antigens. We used as controls 84 sera from healthy individuals or patients without any evidence for disseminated candidosis. The maximum sensitivity for protein antigen of metabolic origin was 67.6%, with an specificity of 77.3%. For the somatic antigen, specificity was higher (83.3%) and positive predictive value was 0.741. We believe that IgG-ELISA gives useful data for diagnosis and follow-up of patients with disseminated candidosis. PMID- 1606222 TI - [Membrane proteins electrophoretic profiles study applied to Neisseria gonorrhoeae epidemiology]. AB - The analysis of electrophoretic profiles of membrane proteins is one of the epidemiological methods of bacterial typing. The profiles of membrane proteins of 95 isolates were studied for valuing their usefulness in the epidemiology of N. gonorrhoeae. The results were compared with the obtained using other characterization methods (auxotyping, serotyping and antimicrobial sensibility). The proteins I and II (PI and PII) showed clear differences between isolates. Only protein-I (PI) with constant molecular weight for each isolate was valid to discriminate between strains. It was observed correlation between serovariety IA and molecular weight of PI 33.6-36 kD, and the serovariety IB with molecular weight 35.5-37 kD. Though it wasn't possible discriminated between the different serovarieties. It was proved a sensibility decrease to penicillin, tetracycline and cloramfenicol in those strains with molecular weight of PI greater than 35.5 kD (serogroup WII/WIII). In the 80% of the isolates considered multiple antibiotic-resistant it was observed a significant increase of the membrane protein dough of 52 kD. All the strains with this protein increased were multiple antibiotic-resistant. PMID- 1606223 TI - [Acute symptomatic HIV infection. Report of 10 cases]. AB - BACKGROUND: The diagnosis of acute HIV infection must rely in the demonstration of a significant increase in antibody titers against HIV together with the timely development of clinical symptoms. The percentage of cases with symptomatic acute HIV infection is currently unknown. METHODS: We performed a retrospective review of all patients admitted to Internal Medicine and Infectious Diseases department of a General Hospital in a three-year period. The presence of HIV-antibodies was assessed by means of ELISA, indirect immunofluorescent test and Western blot technique. RESULTS: Among a total number of 1110 patients, we found 10 (0.9%) that were considered as having an acute symptomatic HIV infection. Clinical presentation was as follows: mononucleosis-like syndrome, 7 patients; aseptic meningitis, 1 patient; polirradiculoneurophaty and coreoatetosis, 1 patient and esophageal candidiasis, 1 patient. Transmission of infection was heterosexual contact in 60% of cases. Four patients developed a transient skin rash, four had oral candidiasis and low platelet count was detected in 6 cases. The presence of circulating HIV antigen could be demonstrated in 7 patients, and the change in antibody titer was recorded with an 11 +/- 2 weeks span. CONCLUSIONS: The incidence of symptomatic HIV acute infection was only 0.9% in our study. The high number of patients with heterosexual transmission and low platelet counts in our series is remarkable. PMID- 1606224 TI - [Rhodococcus equi in HIV infected patients: 2 new cases]. AB - We reported two HIV infected patients with bacteremia and pneumonia due to Rhodococcus equi. None of them had suffer any opportunistic infection before this episode. Clinical presentation includes respiratory tract symptoms of subacute onset and fever. The X-ray examination in both cases revealed pneumonia and lung abscess in upper lobes as well as lung infiltrates in other lobes. The microorganism was isolated in lung fine needle aspiration, bronchoalveolar lavage and blood cultures in both cases. One patient died and the other was under antibiotic treatment 5 months after discharge. The therapeutic options in this infection must include the use of at least two different antibiotics to which the microorganism is sensitive, and for a prolonged period of time. Surgical treatment should be considered if the evolution is poor. PMID- 1606225 TI - [Renal tuberculosis treated with rifampicin, isoniazid and ofloxacin]. AB - We describe the results of eight patients with renal tuberculosis treated with rifampin, isoniazid and ofloxacin. Ofloxacin was given orally, 200 mg b.i.d. for 6 months. During the first three months, rifampin (600 mg/daily) and isoniazid (330 mg/daily) were added. All M. tuberculosis strains isolated were sensitive to ofloxacin (MIC 1 mg/l). Follow-up cultures turned to be negative rapidly (during the first month of therapy), and no untoward effects were recorded. All patients had a 12-months follow-up period, and all were clinically cured. The treatment used was well accepted by all patients. PMID- 1606226 TI - [Digoxigenin-labelled probes for detection of TEM-type beta-lactamases using the PCR technique]. AB - BACKGROUND: Production of DNA probes is time-consuming and inefficient. We have developed a method for the obtention of digoxigenin-labeled probes to detect TEM type betalactamases using the polymerase chain reaction. The amplification product was a 516 bp fragment internal to bla-TEM-1 from pBR 322. METHODS: The techniques developed included extraction of plasmid DNA by lisis by alkali, electroelution, electrophoresis in agarose gels, polymerase chain reaction and hydridization with a DNA probe digoxigenin labeled. RESULTS: We obtained by polymerase chain reaction 1500 ng of probe using 1 ng of target DNA. Developing classic methods the amount of probe was 75 ng from 1 microgram of target DNA. The time to obtain the probe was 3 hours, instead of a week with other methods. CONCLUSIONS: We conclude that polymerase chain reaction is a good alternative to classic methods to obtain digoxigenin-labeled DNA probes. PMID- 1606227 TI - [Usefulness of studies of susceptibility of ampicillin, carbenicillin, cefalotin and colistin as a presumptive identification system for the Aeromonas sp. group]. AB - We have studied the restricted antibiotic susceptibility tests for 180 strains belonging to mesophilic Aeromonas sp. isolated from stools samples. Strains has been identified as follows: A. caviae (64.6%), A. hydrophila (17.7%) and A. sobria (17.7%). Antibiotics tested were ampicillin (10 micrograms), carbenicillin (100 micrograms), cephalotin (30 micrograms) and colistin (10 micrograms), by means of agar diffusion tests (disk-plate). We identified four different patterns of antibiotic susceptibility. The most frequent pattern (pattern #1) (77.8%) is characterized by susceptibility only to colistin, and was predominant among A. caviae strains (80%). Pattern #2 (susceptibility to cephalotin and colistin) was found in 18.9% of strains, being predominant in A. sobria (88.2%). We confirm the higher susceptibility of A. sobria sp. to cephalotin as well as the possibility that these different patterns might be used as screening method for species identification among mesophilic group of Aeromonas. PMID- 1606228 TI - [Diagnostic value of enzymatic detection of serum mannose in invasive candidiasis]. AB - The usefulness of a commercial test for mannose detection in the diagnosis of invasive candidosis was evaluated. Serum mannose was observed in 20 of 22 patients with invasive candidal infection, in a concentration greater than or equal to 60 mumol/l. In 68.2% of them, serum mannose concentration was significant (greater than or equal to 60 mumol/l). The specificity of the test was 91.8%. Efficiency, predictive value positive and negative were 77.5, 58.8 and 94.6%, respectively. PMID- 1606229 TI - [Swelling in right wrist of long development]. PMID- 1606230 TI - [Ring shaped erythema after tick bite]. PMID- 1606231 TI - [Prosthetic valve endocarditis]. PMID- 1606232 TI - [Presence of whitish microorganisms in anal margins and feces]. PMID- 1606233 TI - [Prevalence of Borrelia burgdorferi infection in an area of Barcelona]. PMID- 1606234 TI - [Incidence of pseudo-appendicitis syndrome caused by Yersinia enterocolitica]. PMID- 1606235 TI - [No detection of HTLV-1 antibodies in two rural populations]. PMID- 1606236 TI - [Conjunctival transmission of boutonneuse fever]. PMID- 1606237 TI - [Mononucleosis-like syndrome from adenovirus with typical bacterial analytical characteristics]. PMID- 1606238 TI - [Current treatment of pneumococcal meningitis]. PMID- 1606239 TI - A theoretical basis for conditional probability analyses of neural discharge activity. AB - A theory has been developed which allows the estimation of the probability density of a discharge, given that an arbitrary condition is fulfilled. It is shown that the common methods for the evaluation of a post-stimulus time (PST) histogram and a hazard function can be considered as special applications of this theory. Whereas the usual hazard function shows how the probability of a discharge depends on the time elapsed since the last discharge, generalized hazard functions proposed in the present paper allow to reveal also the influence of the last but one discharge, the last but two discharge, and so on. In contrast to the usual method for the estimation of a hazard function, the applicability of the procedures proposed here is not restricted to stationary discharge activity. Some elementary applications are illustrated by analysing simulated discharge activity mimicing the response of a single auditory-nerve fiber to a high intensity tone burst. PMID- 1606240 TI - A unified neural network [corrected] model of spatiotemporal processing in X and Y retinal ganglion cells. I. Analytical results. AB - This work presents unified analyses of spatial and temporal visual information processing in a feed-forward network of neurons that obey membrane, or shunting equations. The feed-forward shunting network possesses properties that make it well suited for processing of static, spatial information. However, it is shown here that those same properties of the shunting network that lead to good spatial processing imply poor temporal processing characteristics. This article presents an extension of the feed-forward shunting network model that solves this problem by means of preprocessing layers. The anatomical interpretation of the resulting model is structurally analogous to recently discovered data on a retinal circuit connecting cones to retinal ganglion cells through pairs of push-pull bipolar cells. Mathematical analysis of the lumped model leads to the hypothesis that X and Y retinal ganglion cells may consist of a single mechanism acting in different parameter ranges. This hypothesis is confirmed in the companion article, wherein the model--in conjunction with a nonlinear temporal adaptation mechanism--is used to reproduce experimental data of both X and Y cells by simple changes in morphological and physiological parameters. PMID- 1606241 TI - A unified neural network model of spatiotemporal processing in X and Y retinal ganglion cells. II. Temporal adaptation and simulation of experimental data. AB - This article makes use of a push-pull shunting network, which was introduced in the companion article, to model certain properties of X and Y retinal ganglion cells. Input to the push-pull network is preprocessed by a nonlinear mechanism for temporal adaptation, which is ascribed here to photoreceptor dynamics. The complete circuit is used to show that a simple change in receptive field morphology within a single model equation can change the network's response characteristics to closely resemble those of either X or Y cells. Specifically, an increase in width of the receptive field center mechanism is sufficient to account for generation of on-off (Y-like) instead of null (X-like) responses to modulated gratings. In agreement with experimental data, the Y cell on-off response is independent of spatial phase. Also, the model accurately predicts that on-off responses can be observed in X cells for particular stimulus configurations. Taken together, the results show how the retina combines individually inadequate modules to efficiently handle the tasks required for accurate spatial and temporal visual information processing. The model is also able to clarify a number of controversial experimental findings on the nature of spatiotemporal visual processing in the retina. PMID- 1606242 TI - Self-organizing maps: stationary states, metastability and convergence rate. AB - We investigate the effect of various types of neighborhood function on the convergence rates and the presence or absence of metastable stationary states of Kohonen's self-organizing feature map algorithm in one dimension. We demonstrate that the time necessary to form a topographic representation of the unit interval [0, 1] may vary over several orders of magnitude depending on the range and also the shape of the neighborhood function, by which the weight changes of the neurons in the neighborhood of the winning neuron are scaled. We will prove that for neighborhood functions which are convex on an interval given by the length of the Kohonen chain there exist no metastable states. For all other neighborhood functions, metastable states are present and may trap the algorithm during the learning process. For the widely-used Gaussian function there exists a threshold for the width above which metastable states cannot exist. Due to the presence or absence of metastable states, convergence time is very sensitive to slight changes in the shape of the neighborhood function. Fastest convergence is achieved using neighborhood functions which are "convex" over a large range around the winner neuron and yet have large differences in value at neighboring neurons. PMID- 1606243 TI - Self-organizing maps: ordering, convergence properties and energy functions. AB - We investigate the convergence properties of the self-organizing feature map algorithm for a simple, but very instructive case: the formation of a topographic representation of the unit interval [0, 1] by a linear chain of neurons. We extend the proofs of convergence of Kohonen and of Cottrell and Fort to hold in any case where the neighborhood function, which is used to scale the change in the weight values at each neuron, is a monotonically decreasing function of distance from the winner neuron. We prove that the learning dynamics cannot be described by a gradient descent on a single energy function, but may be described using a set of potential functions, one for each neuron, which are independently minimized following a stochastic gradient descent. We derive the correct potential functions for the one- and multi-dimensional case, and show that the energy functions given by Tolat (1990) are an approximation which is no longer valid in the case of highly disordered maps or steep neighborhood functions. PMID- 1606244 TI - Complex dynamics underlying the human electrocardiogram. AB - Sequences of different human cardiac rhythms terminating in ventricular fibrillation have been studied, both qualitatively and quantitatively, with methods of nonlinear dynamics. The analysis has been applied to ECG epochs belonging to rhythms of increasing electrocardiographic irregularity: from sinus rhythm to prefibrillatory rhythms and then to ventricular fibrillation. The phase portraits of these rhythms have been reconstructed from the ECG recording with the time-delay technique, and their correlation dimensions have been estimated with the algorithm of Grassberger and Procaccia (1983a, b). Different cardiac rhythms exhibit different correlation dimensions that describe the corresponding degrees of complexity. The correlation dimension increases as one proceeds from sinus rhythm to fully developed ventricular fibrillation via intermediate rhythms. The fully developed ventricular fibrillation shows the highest degree of complexity. The dimensional analysis supports the existence of complex dynamics underlying different cardiac rhythms and reveals an increase in dimensional complexity corresponding to an increase in electrocardiographic irregularity. Our results indicate that nonlinear dynamics may be used to assess various dynamic states of the heart and may offer a non-invasive tool to investigate the complex dynamic phenomena occurring during arrhythmia. PMID- 1606245 TI - "Live" neuron and optimal learning rule. AB - A concept of the live unit as an automatic regulation system with a few admissible states areas in the space of states is considered. Energetic profit of oscillatory behavior consisting in the consecutive transitions of system from one admissible states area to another is shown. It is stated, that external disturbances cause the energy consumption of oscillatory system to decrease. On the basis of this concept and some neurophysiological data, the "live" energy consuming nonlinear three-state neuron model is proposed and the existence of energy optimal generation frequency v(opt) is proved. For the realization of tendency to v(opt) the optimal learning rule is proposed, which provides unsupervised learning and interlinked short-term and long-term memories with forgetting. The model proposed explains the genesis of neural network, is promising in the sense of network self-organization and allows to solve the problem of internal activity in the researches on artificial intelligence. PMID- 1606246 TI - Self-organization of day cycle and hierarchical associative memory in "live" neural network. AB - The "live" neural network model is proposed on the basis of "live" neuron model and optimal learning rule. By means of numerical simulation the initial stages of neural network self-organization have been shown: (1) the formation of two activity forms, which are identified with sleep and awaking, and (2) the self organization of hierarchical associative memory when feeding a receptor excitation to the neural network. The energetic profit of self-organization is demonstrated. The formation of neural ensembles, playing the role of generalized neurons, is obtained. PMID- 1606247 TI - Spatio-temporal convergence (STC) in otolith neurons. AB - It has been recently demonstrated that some primary otolith afferents and most otolith-related vestibular nuclei neurons encode two spatial dimensions that can be described by two vectors in temporal and spatial quadrature. These cells are called broadly-tuned neurons. They are characterized by a non-zero tuning ratio which is defined as the ratio of the minimum over the maximum sensitivity of the neuron. Broadly-tuned neurons exhibit response gains that do not vary according to the cosine of the angle between the stimulus direction and the cell's maximum sensitivity vector and response phase values that depend on stimulus orientation. These responses were observed during stimulation with pure linear acceleration and can be explained by spatio-temporal convergence (STC) of primary otolith afferents and/or otolith hair cells. Simulations of STC of the inputs to primary otolith afferents and vestibular nuclei neurons have revealed interesting characteristics: First, in the case of two narrowly-tuned input signals, the largest tuning ratio is achieved when the input signals are of equal gain. The smaller the phase difference between the input vectors, the larger the orientation differences that are required to produce a certain tuning ratio. Orientation and temporal phase differences of 30-40 degrees create tuning ratios of approximately 0.10-0.15 in target neurons. Second, in the case of multiple input signals, the larger the number of converging inputs, the smaller the tuning ratio of the target neuron. The tuning ratio depends on the number of input units, as long as there are not more than about 10. For more than 10-20 input vectors, the tuning ratio becomes almost independent of the number of inputs. Further, if the inputs comprise two populations (with different gain and phase values at a given stimulus frequency), the largest tuning ratio is obtained when the larger population has a smaller gain. These findings are discussed in the context of known anatomical and physiological characteristics of innervation patterns of primary otolith afferents and their possible convergence onto vestibular nuclei neurons. PMID- 1606248 TI - Relaxation network for Gabor image decomposition. AB - The so-called "simple cells" in layer IV of feline primary visual cortex have been shown to have Gabor function spatial receptive field profiles (RFP's). Since Gabor functions are not mutually orthogonal, the decomposition of an image into Gabor function coefficients is usually performed by minimising some measure of the error between the original image and that reconstructed from the coefficients. A cortical relaxation model is proposed which performs this minimisation implicitly, and is used to examine the biological relevance and feasibility of reconstruction error minimisation. PMID- 1606249 TI - Mutagenicity of airborne particulates in Sagamihara City. AB - Airborne particulates in Sagamihara city were collected on quartz fibre filters using a high-volume air sampler for 14 days in each month from July 1984 to June 1985. Organic components in airborne particulates were extracted by the ultrasonic extraction method using benzene-ethanol (3:1 v/v) as an extracting solvent. The mutagenecities of airborne particulates extract were measured by the pre-incubation method using Salmonella typhimurium strains TA100 and TA98 with and without S-9mix. The concentration of airborne particulates was nearly the same level throughout the survey period, but the content of extract in particulates of winter was higher than those of other seasons. All the airborne particulates extracts showed positive mutagenic response to both strains with and without S-9mix. The average of mutagenic activities (revertants/m3 air) in winter was significantly higher than those in summer and spring. Furthermore, mutagenic activities fluctuated sharply in one month from several to ten times compared with the normal level, depending upon sampling days, and tended to be lower on Sundays and holidays in summer and new year holidays. In many days mutagenic activities without S-9mix were comparatively higher than those with S-9mix. The existence of nitroarene was surveyed using TA98NR strain. Nitroarene was found to be higher concentration in summer than in winter. PMID- 1606250 TI - Ultrastructure of goat testes: intercellular bridge between germ cells. AB - The fine structure of intercellular bridge (ICB) of goat germ cells was studied using testicular samples fixed by perfusion. In the seminiferous tubules, the ICBs were observed between sister cells of spermatogonia, spermatocytes and spermatids. As a result of incomplete division of germ cells, the ICB first appeared as a midbody containing a remnant of the bundle of microtubules (spindle fibers). These microtubules then disappeared and were replaced by a shutter apparatus which was composed of multiple lamellar cisternae (bridge-partitioning complex). The inner part of the ICB was reinforced with a layer of electron dense mass (bridge density) which persisted up to the residual cytoplasm of spermiation. After complete reconstruction of the sister cells, the cisternae of the bridge-partitioning complex disappeared and the channel of the ICB was opened. Evidently (see electron micrographs), almost all of the cytoplasmic organelles could pass through the channel of the ICB. In the longitudinal section, the appearance of the ICBs between sister spermatogonia and between sister spermatocytes was observed as a double linear or drum shape, and that between sister spermatids was noticed as a horseshoe-like or concave formation. With the process of spermatogenesis, the ICBs gradually became widened and shortened. The functional significance of the ICB in the goat was discussed. PMID- 1606251 TI - Antitumor activity of Toxoplasma lysate antigen against methylcholanthrene induced tumor-bearing rats. AB - Growth of the tumor autoinduced by 20-methylcholanthrene (MC) in rats was inhibited after administration of Toxoplasma lysate antigen (TLA). The antitumor activity of TLA was most obvious in the early stage of tumoral growth. When TLA was administered to rats before the appearance of tumour, tumor formation was delayed slightly. Histopathological studies revealed dense growths of spindle tumor cells in untreated control rat, while enlarged central necrosis with the infiltration of lymphocytes and neutrophils was apparent in TLA-treated rats. According to the immunohistological examination of tumor tissue with anti-Thy-1 antibody, the rats treated with TLA showed large Thy-1 positive granular cells, whereas the untreated rats indicated only a few small Thy-1 positive cells. These observations indicate that TLA is a useful modifier of biological responses to MC induced tumors. PMID- 1606252 TI - An outbreak of copper poisoning in Mute swans (Cygnus olor). AB - Eight of 9 Mute swans (Cygnus olor) untied in the river acrossing the central part of Tottori-city died within the period of 40 days of summer in 1989. Seven of 8 Mute swans were pathologically examined. In all swans many yellowish-brown to greenish-brown granules were found in the cytoplasm of hepatocytes. The granules were intensely stained with rhodanine copper stain, schmorl method, and Berlin blue stain. Ultrastructurally, many lysosomes increased in size and density in the cytoplasm of hepatocytes. Other three swans, that died at other places, were served as controls. In control swans, many brown granules intensely stained with schmorl method and Berlin blue stain were also found in hepatocytes, but the number of rhodanine-positive granules were fewer than those of the affected cases. X-ray qualitative analysis showed three peaks corresponding to copper, zinc and sodium in the liver of the affected and control swans. Quantitative analysis demonstrated that mean hepatic copper concentration of the affected group was significantly higher than that of control group (P less than 0.01). From these findings, we concluded that all of 7 Mute swans died of copper poisoning. PMID- 1606253 TI - Chemotactic activity of hemocytes derived from two marine neritid gastropod molluscs, Nerita albicilla and Heminerita japonica, to Vibrio parahaemolyticus and Escherichia coli strains. AB - Hemocytes of two marine neritid gastropods, Nerita albicilla and Heminerita japonica, were attracted chemotactically to live Vibrio parahaemolyticus and Escherichia coli strains. Chemotactic attraction of N. albicilla hemocytes was enhanced in the presence of N. albicilla plasma, while that of H. japonica hemocytes was not enhanced in the presence of H. japonica plasma. Chemotactic activity of the hemocytes seems to participate in the rapid elimination of V. parahaemolyticus from these gastropods. PMID- 1606254 TI - Simultaneous determination of tetrahydrofolate and N5-methyltetrahydrofolate in pig plasma by high-performance liquid chromatography with electrochemical detection. AB - An analytical method for measurement of tetrahydrofolate (THF) and N5 methyltetrahydrofolate (5MF) in pig plasma by the high performance liquid chromatography and electrochemical detection is described. The plasma sample was deproteinized by perchloric acid and the supernatant was analyzed using the following conditions; (a) phenyl bonded phase column as an analytical column; (b) mobile phase consisting of 20 mM acetate buffer (pH 3.6) containing 0.1 mM EDTA and acetonitrile (96.5:3.5, v/v); (c) an applied potential of +300 mV. Under the above condition, both peaks of THF and 5MF in the plasma were well separated. The detection limits of THF and 5MF were 0.15 and 0.13 ng/ml, respectively, at S/N = 3. The recoveries of THF and 5MF from the plasma spiked with standard THF and 5MF were 77.6 +/- 2.1% and 83.0 +/- 1.7% (mean +/- S.D.), respectively. PMID- 1606256 TI - Higher sensitivity of LEC strain rat in radiation-induced acute intestinal death. AB - LEC strain rats (LEC rats), which have been known to develop hereditarily spontaneous fulminant hepatitis 4-5 months after birth, were highly sensitive to whole-body X-irradiation as compared to WKAH strain rats (WKAH rats). Radiation induced acute intestinal death occurred at doses higher than 6.5 Gy in LEC rats, and at doses higher than 12.8 Gy in WKAH rats, respectively. By the probit analysis of survival data, it was shown that the LD50/7 value of LEC rats was estimated to be 7.03 Gy which was significantly lower than that (12.99 Gy) of WKAH rats. Histopathological examinations of small intestines from LEC rats 2 days after irradiation at the dose of 8.5 Gy showed severe epithelial death together with edema, whereas little or no significant changes were noted in intestinal epithelium of 8.5 Gy-irradiated WKAH rats. These results suggest that the radiosensitivity of LEC rats to ionizing radiation appears to be higher than that of other strains of rats. PMID- 1606255 TI - Bacterial flora of the respiratory tracts in chickens with a particular reference to Lactobacillus species. AB - The effects of three different types of breeding such as isolator, floor, and cage breedings on the bacterial flora of the respiratory tracts (nasal cavity, tongue, pharygolarynx, trachea and air sac) in chickens were determined. Total viable bacterial numbers on the nasal mucus of chickens in the isolator breeding as control group (Group A) aged of 14 days were 10(4.6)/g of autopsy specimen (wet weight), 10(5.7)/g of sample in the cage breeding (Group B) aged of 28 days, and 10(7.0)/g of sample in the floor breeding (Group C) aged of 28 days. Staphylococci and micrococci were predominant bacteria in the nasal cavities of all groups. Total viable numbers of tongue and pharygolarynx were from 10(5.4) to 10(6.5)/g of autopsy specimen. Lactobacilli were the predominant bacteria in pharyngolarynx of chickens. The incidence of staphylococci and micrococci in trachea was lower than those in the another regions. Staphylococci and micrococci dominated in the air sacs of two groups (B and C), but the number and incidence of lactobacilli in the air sacs of chickens were lower than those in the another respiratory tracts. The only clostridia isolation in the air sacs of Group A was observed. A total of 75 strains of Lactobacillus species was isoalted from all respiratory organs and intestine of chickens. These strains were divided into 19 groups. Lactobacillus salivearius subsp. salivarius was the predominant lactobacilli isolated from tongue and pharyngolarynx. Most of isolates from the chicken intestines were mainly identified as the L. acidophilus group and L. reuteri.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606257 TI - DNA fragmentation and cytotoxicity by recombinant human tumor necrosis factor in L929 fibroblast cells. AB - Induction of cell DNA fragmentation by treatment of recombinant human Tumor Necrosis Factor alpha (rhTNF alpha) was examined by using mouse L929 cells derived from mouse fibroblast cells. The amount of DNA fragments derived from rhTNF alpha-treated cells, detected by alkaline elution technique, was smaller than that derived from X-irradiated cells. The rhTNF alpha caused the DNA fragmentation depending on its incubation time and concentration. The DNA damage caused by rhTNF alpha treatment correlated with its cytotoxicity. This result suggested that the DNA fragmentation is one of causes of cell death. The treatment with proteinase K of DNA obtained from rhTNF alpha-treated cells did not increase the amount of DNA fragmentation, which indicates that rhTNF alpha causes DNA-fragmentation but not DNA-protein cross-linking. PMID- 1606258 TI - Protective effects of thiol compounds on chromate-induced cytotoxicity in HeLa cells. AB - The effects of several thiol compounds on the cytotoxicity induced by chromate (potassium dichromate) were examined. HeLa cells were incubated in Eagle's minimum essential medium (MEM) with or without the chromate alone, or with both chromate and any one of L-cysteine ethyl ester (LCysEE), L-cysteine methyl ester (LCysME), N-acetyl-L-(+)-cysteine, 2,3-dimercaptosuccinic acid (DMSA), 2, 3 dimercapto-1-propanesulfonic acid (DMPS), or dithiothreitol. After a given period of incubation, the number of viable cells was counted using the trypan blue exclusion test and the chromium content of the cells was estimated by atomic absorption spectrophotometry. The results obtained were as follows. 1) Chromate induced cytotoxicity evaluated by inhibition of cell growth at 3 days of incubation was diminished by all of the thiol compounds tested when the cells were incubated in MEM with 2.5 to 10.0 microM chromate and 25 to 100 microM thiol compounds. 2) All of the thiol compounds produced a concentration-dependent reduction of chromate when a solution of the thiol compound (12.5 to 100 microM) was mixed with a solution of chromate (10 microM) in distilled water. 3) When cells were incubated in MEM with both 10 microM chromate and 25 to 100 microM thiol compounds, the chromium content of the cells at 6 hr of incubation was decreased in a concentration-dependent manner. 4) When these thiol compounds were added to MEM 1 hr before or after chromate, no or little protective effects of these thiol compounds against chromate-induced cytotoxicity and chromium uptake by the cells were observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606259 TI - Developmental process of Cryptosporidium in the intestine and bursa of Fabricius of chickens. AB - The developmental process of a Cryptosporidium isolated in Japan in the chicken intestine was investigated by scanning (SEM) and transmission electron microscopies (TEM). The parasites were detected in the ileum, cecum, colon, cloaca and bursa of Fabricius (BF). The intensity of infection tended to peak later in the BF than ileum. Trophozoites and schizonts were detected in all the portions of intestine, and were dominant in the developmental stages. Although macrogamonts were the secondary dominant stage, they were absent in the ileum and cecum at 60 hr postinoculation (PI). A few microgamonts were detected in the ileum at 36 hr PI and in the BF on day 19 PI. Oocysts were observed in the ileum at 48 hr PI and in the BF on day 19 PI. PMID- 1606260 TI - Establishment of an IL-2-dependent bovine T cell line and an assay of lymphocyte response inhibition in leukemic bovine serum. AB - The mechanism of immunosuppression induced by leukemic bovine serum was investigated with respect to lymphokine reactions using an interleukin 2 (IL-2) dependent bovine T cell line generated from bovine peripheral blood lymphocytes (PBLs). The suppression of concanavalin A (con A)-induced PBL blastogenesis was observed at a high rate in leukemic cattle sera. The growth of IL-2-dependent bovine T cells and IL-2 production from con A-induced bovine PBLs were also inhibited by these sera, and particularly, the latter was correlated significantly to the degree of lymphocyte blastogenesis by the mitogen. Therefore, the lesser sensitivity of lymphocytes to IL-2 and the reduced IL-2 production by activated lymphocytes seem to play a role in suppressing the lymphocyte reaction. PMID- 1606261 TI - Time-related morphological changes of porcine ovarian granulosa cells incubated with urea-EDTA solution. AB - Morphological profiles of porcine granulosa cells incubated with 10 mM Tris-HCl containing 1 M urea and 5 mM EDTA (urea-EDTA solution) were investigated. The percentages of granulosa cells incorporating the dye, trypan blue on incubation with urea-EDTA solution did not change during the initial 30 min. Thereafter, granulosa cells gradually took up the dye throughout the incubation. The amount of protein released from granulosa cells increased dramatically during initial 15 min of incubation, but decreased during the following 15-30 min of incubation. Thereafter, the amount of proteins released from granulosa cells increased gradually again. The releasing profile of 51Cr-bounded substances in granulosa cells increased markedly during the initial 15 min of incubation, and decreased during the next 15 min of incubation. Subsequently the amount of 51Cr released was enhanced. The min of incubation. Subsequently the amount of 51Cr released was enhanced. The plasma membranes of granulosa cells remained intact at 30 min of incubation, although chromatin clusters of granulosa cells disappeared. Thereafter, a number of cells showed signs of degeneration, including broken plasma membrane and cytolysis. The present study revealed that urea-EDTA solution is useful in extracting materials from porcine granulosa cells. The majority of the materials extracted from granulosa cells during the initial 30 min of incubation with urea-EDTA solution is considered to be from the cell surfaces and/or intercellular matrix. PMID- 1606262 TI - Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blotting analyses of ureaplasmas isolated from dogs. AB - To define the antigenic relatedness among unspeciated ureaplasma strains isolated from dogs, four canine ureaplasma isolates representing four serotypes were compared with the five type strains of the established species in Genus Ureaplasma by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Although all the strains showed distinct electrophoretic patterns by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the Western blotting patterns were much more distinct. By Western blotting, the five type strains of established species reacted strongly with homologous antisera and showed slight cross reactions with heterologous antisera. However canine strains which showed little cross reactions with the established Ureaplasma species showed a variety of cross reactions among the four canine serotypes used. PMID- 1606263 TI - Aggressive fibromatosis in a cat. AB - A case of aggressive fibromatosis (extra-abdominal desmoid) found in a 9-month old male mixed breed cat is described. The right forearm was almost completely effaced by fibrous tissue and there were some tumours in the area from the shoulders to the mandible. These tumour-like tissues were composed of abundant collagen fibres and sparse numbers of well-differentiated fibroblasts, whereas their growing pattern was aggressive and non-encapsulated. There was dense growth of immature fibroblasts and multinucleated giant cells in some areas. Vimentin immunohistochemistry and electron microscopy suggested that the giant cells had close relation to the fibroblasts, and such areas may be the sites of cell proliferation. This case is different from nodular fasciitis and may be a proliferative disorder induced by feline oncogenic retrovirus. PMID- 1606264 TI - Radiographic investigation of ulcerative lesions in the carpal joint in Japanese black calves. PMID- 1606265 TI - Distribution of Staphylococcus species on animal skin. PMID- 1606266 TI - Some observations on mycoplasma-cidal activity of horse serum. PMID- 1606267 TI - Serotyping of Haemophilus paragallinarum isolated in Malaysia. PMID- 1606268 TI - Sensitive method for the detection of antibodies to infectious hematopoietic necrosis virus. PMID- 1606269 TI - Theileria sergenti infection in dairy cattle. PMID- 1606270 TI - HPLC determination of adenine compounds as fluorescent derivatives in canine red blood cells. PMID- 1606271 TI - Cardiopathological observation of bifascicular block in an aged cat. PMID- 1606272 TI - Preliminary experiment for detection of penicillinase by enzyme-linked immunosorbent assay and western blotting technique. PMID- 1606273 TI - Solid-phase extraction of estrogens from bovine blood plasma. PMID- 1606274 TI - In pursuit of patient satisfaction. PMID- 1606275 TI - Health habits of children. PMID- 1606276 TI - Twelve principles for national health insurance reform. PMID- 1606277 TI - Ethics and Medicaid: a new look at an old problem. AB - Recent proposals to reform Medicaid, driven primarily by the need for cost containment, rarely pay explicit attention to values. This paper presents the Medicaid Values Framework, the authors' interpretation of a set of societal ideals embodied in Title XIX of the Social Security Amendments of 1965. The Framework comprises seven interlocking values that are stratified into three interdependent tiers--access, quality, and equity. We use the access and equity tiers to analyze treatment of Aid to Families with Dependent Children (AFDC) and Supplemental Security Income (SSI) recipients under Medicaid. We document striking inequities in eligibility standards and in funding for the two groups- inequities that unexpectedly fail to translate into marked disparities in access to Medicaid. In conclusion, we comment on why the present inequities exist and why they are ethically unacceptable. PMID- 1606278 TI - Health care access and advocacy for immigrant and other underserved elders. AB - Little is known about health care access and advocacy for elders of color, and even less is known about immigrant elders, whose growing number is the major reason that almost one of every three older persons in the U.S. by the year 2050 will be an elder of color. This paper explores a number of access barriers faced by underserved elders, including inequitable long-term care services and counterproductive "colorblind" approaches to caregiving. It also addresses barriers, such as problematic immigration policies, that present particular challenges to elderly immigrants. While available materials provide baseline information and help providers learn about underserved elders, real change in how target populations gain access to health and social services comes when providers make explicit efforts to improve the accessibility and quality of services. PMID- 1606279 TI - Therapeutic problems in the management of elderly patients with tuberculosis. AB - Adverse reactions to antituberculous drugs are more common in the elderly. With the increasing numbers of elderly people and the higher incidence of tuberculosis in this age group, clinicians will encounter more therapeutic problems in the use of antituberculous drugs than in younger patients. Existing studies regarding pharmacological and non-pharmacological factors which may predispose to increased adverse effects in the elderly are reviewed. Reduced clearances of isoniazid and rifampicin at steady state, possible increase in free drug concentration of drugs normally bound to albumin, possible differences in disposition of toxic metabolites such as hydrazine, concomitant administration of both isoniazid and rifampicin, poor nutrition and severity of the disease in the elderly may be contributing factors. Further studies in these areas should provide clearer guidelines on whether dosages or drug combinations should be modified in elderly patients with tuberculosis. PMID- 1606281 TI - Counterfeit medicines--the case for action. PMID- 1606280 TI - The Chinese restaurant syndrome: a reappraisal of monosodium glutamate's causative role. PMID- 1606282 TI - A review of the literature on benign intracranial hypertension associated with medication. PMID- 1606283 TI - Implications of recommendations from the International Conference on Harmonization (ICH) for the safety evaluation of new medicines involving animal studies for the pharmaceutical industry. AB - Based upon the recommendations given by the ICH outlined in this document, it is proposed that: 1. In rodents, single dose toxicity studies should be conducted using as few animals as possible. 2. Single dose toxicity studies in non-rodents will not be performed except possibly as a component of dose escalation studies. 3. Recovery animals on repeat dose studies will not be monitored for delayed toxicity. 4. Twelve month rodent studies will not be performed. 5. Twelve month non-rodent studies will be performed for chronic therapies except in the few circumstances when the ICH exclusion criteria can be met. 6. EEC protocols for reproductive toxicology studies will be followed until a new guideline is issued. 7. Consultation with regulatory authorities, especially the FDA, may be required to set the doses to be used in carcinogenicity studies. PMID- 1606284 TI - Counterfeit drugs: implications for health. PMID- 1606285 TI - Double bolus administration of the novel recombinant plasminogen activator BM 06.022 improves coronary blood flow after reperfusion in a canine model of coronary thrombosis. AB - Reocclusion of coronary arteries is a major problem after successful thrombolysis in patients with acute myocardial infarction. We evaluated in a canine model of coronary thrombosis which is known to elicit reocclusion, whether an increased single i.v. bolus dose or two boli of the novel t-PA variant BM 06.022 improved coronary blood flow after reperfusion compared to i.v. injection of a standard single dose of BM 06.022. Double bolus administration, but not an increased single bolus dose of BM 06.022 significantly increased the maximum achieved coronary blood flow, prolonged the cumulative patency time, maintained blood flow at the end of the experiments, and reduced residual thrombus wet weight. Thus, double bolus administration improves coronary blood flow after reperfusion in the dog. PMID- 1606286 TI - Impaired release of tissue plasminogen activator (t-PA) following DDAVP infusion in von Willebrand's disease with low platelet von Willebrand factor content. AB - Tissue plasminogen activator (t-PA) and von Willebrand factor (vWF) are both released by vascular endothelial cells after the infusion of DDAVP. Such release has not been observed in patients with severe von Willebrand's disease (vWD). In the present work we demonstrate that the degree of simultaneous DDAVP-induced release of t-PA and vWF, in patients with vWD, is strictly related to the platelet vWF content. Twelve patients with type I, and three patients with type III vWD were studied. The type I vWD group included three patients with reduced platelet vWF content (platelet-low) and nine patients with normal levels (platelet-normal). In all patients studied the plasma t-PA levels were within the normal range. No significant change in either t-PA or vWF was observed after DDAVP in the patients with undetectable levels of platelet vWF (type III vWD). A mild increase was found in those patients with type I platelet-low, while in type I platelet-normal vWD the response was similar to that observed in normal subjects. The release of the two molecules appeared, therefore, to be linked to platelet vWF content and the rates of increase in both t-PA and vWF were similar in each group of patients studied. Since platelets are regarded as a tissue compartment of vWF our findings seem to suggest that the presence of vWF and its release from endothelial cells is required for a normal concomitant release of t PA. In contrast, post-DDAVP release of vWF seems to be independent from that of t PA since it was normal in a patient with congenital deficiency of t-PA release. PMID- 1606287 TI - A non-occlusive model of arterial thrombus formation in the rat and its modification by inhibitors of platelet function, or thrombin activity. AB - A technically simple model of arterial thrombosis in the rat, induced by a crush injury to the dorsal aorta is described. The mechanical injury to the artery caused deep medial injury and the formation of a platelet-rich thrombus with associated fibrin formation which was assessed both radiometrically and morphometrically. No significant inclusion of erythrocytes was noted in the thrombus. Administration of the platelet inhibitors aspirin, BM 13505 (a thromboxane receptor antagonist) or CGS 12970 (a thromboxane synthase inhibitor) reduced the extent of platelet deposition on the injured vessel, but no decrease in fibrin(ogen) was observed. In contrast, infusion of prostacyclin resulted in reductions in both these components of the thrombus. In studies involving inhibition of thrombin activity, the direct thrombin inhibitor CGP 39393 (recombinant desulphatohirudin) inhibited both the platelet and fibrin(ogen) deposition. The indirect thrombin inhibitors were less effective; unfractionated heparin and low-molecular-weight heparin inhibited both platelet and fibrin(ogen) deposition but only at doses which rendered the blood uncoagulable, as evaluated by the activated partial thromboplastin time. Dermatan sulphate only inhibited platelet deposition. The results suggest that thrombin plays a key role in the initiation of thrombus formation in this experimental model. The agonist prostaglandins (PGG2, PGH2, and TXA2) would appear to have a supporting role in the platelet deposition onto the thrombotic surface but do not have a role to play with respect to fibrin(ogen) deposition. PMID- 1606288 TI - The effect of exercise and heart rate on fibrinolytic activity. AB - The effect of heart rate on plasma fibrinolytic activity was investigated in nine patients with dual chamber cardiac pacemakers before and after 10 min of stimulated tachycardia to 123 beats/min. The results were compared to seven volunteers who performed submaximal exercise to 90% target heart rate and to five of the seven who underwent a second period of exercise to a heart rate of 120 beats/min. During submaximal exercise (mean heart rate 152 beats/min) the median ECLT fell from 248 min (interquartile range 147.5-305) to 90 (55-202) P less than 0.01 and t-PA:Ag increased from 6.1 ng/ml (3.92-7.95) to 9.3 (8.45-12.7), P less than 0.025. PAI and PAI-1:Ag fell from 12.0 IU/ml (5.85-15.5) to 4.1 (1.85 11.67), P less than 0.01, and 9.7 ng/ml (2.8-10.6) to 6.7 (2.1-9.9), P less than 0.01 respectively. A lower level of exercise to 120 beats/min resulted in a reduction in ECLT from 215 min (167.5-228.5) to 135 (116-154), P = 0.05 and an increase in t-PA:Ag from 4 ng/ml (3.07-4.45) to 5.0 (3.3-5.22) P less than 0.05. PAI and PAI-1:Ag fell from 7.6 IU/ml (3.27-8.5) to 7.1 (2.77-7.4) and from 7.7 ng/ml (6.0-7.92) to 6.4 (4.8-7.3) respectively but these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606289 TI - Determination of markers of coagulation activation and reactive fibrinolysis in patients with mechanical heart valve prosthesis at different intensities of oral anticoagulation. AB - In a group of 60 patients with mechanical heart valve prosthesis prothrombin fragment 1 + 2, thrombin-antithrombin III complexes and D-dimer have been determined in order to assess the residual coagulation activation and the extent of the reactive fibrinolysis. The patients were divided into three subgroups of 20 patients each with different intensities of oral anticoagulation as indicated by International Normalized Ratio (INR) values in the ranges 4.8-3.6, 3.5-2.5 and 2.4-2.1. From the two markers of coagulation activation studied (prothrombin fragment 1 + 2 and thrombin-antithrombin III (TAT)) the prothrombin fragment 1 + 2 was dependent on the INR level in all groups, although the median values were still significantly beneath the lower limit of the reference range. The D-dimer concentrations were unexpectedly high with respect to the low coagulation activation levels, as indicated by the D-dimer/TAT and D-dimer/F 1 + 2 ratios. This demonstrates the enhanced presence of fibrin degradation products as a scarcely described side-effect of oral anticoagulation. The anticoagulant properties of fibrin degradation products might contribute partly to the in vivo haemorrhagic risk in high-intensity oral anticoagulation. These results show, inasmuch as the prothrombin fragment 1 + 2 is concerned, that from the laboratory point of view the residual thrombin activity is low enough to be adequate under the therapeutical regimen followed in this study. However, the question of the efficacy of anticoagulation intensities can only be finally answered by clinical trials. PMID- 1606290 TI - Heparin rebound phenomenon--much ado about nothing? AB - Significant postoperative bleeding following open-heart surgery is often ascribed to the so-called heparin 'rebound' phenomenon and as such is treated with additional empiric doses of protamine sulphate. However, inappropriate protamine administration has been reported to be associated with acute pulmonary hypertension. The efficacy of heparin reversal was investigated in 42 patients undergoing open-heart surgery. The standard heparin bolus of 3 mg/kg body weight (4.1 IU/ml blood) administered before cardiopulmonary bypass was countered at the end of bypass using an empirical equivalent (3 mg/kg) of protamine. This regimen resulted in complete heparin neutralization (measured by the Hepcon HMS [Hemotec Inc., Englewood, CO, USA]) 15 min after protamine administration in all 42 patients, but heparin levels (0.4 IU/ml) were transiently detectable (duration less than 1 h) in six (14%) of the 42 cases 2 h later. Twenty-four hour postoperative bleeding in these patients did not differ significantly from that seen in patients who did not exhibit heparin rebound. Similarly, the thrombelastographic profiles (at 15 min and 2 h post-operation) and coagulation screen (prothrombin time, activated partial thromboplastin time, activated clotting time and platelets) did not differ significantly from those of non rebound patients. The significance, if any, of the phenomenon of heparin rebound following cardiac surgery remains to be elucidated, and, until such time, conservative administration of protamine in response to 'rebound' is recommended. PMID- 1606291 TI - Fibrinolysis and fibrinogenolysis in patients with thrombotic disease. AB - In order to assess the fibrinolytic state in thrombotic disease, plasma levels of fibrin degradation products (FbDP) and fibrinogen degradation products (FgDP) were measured in 126 patients with a variety of thrombotic diseases. Mean plasma concentrations of both FbDP and FgDP were significantly elevated in patients with thrombotic disease as compared with healthy subjects. Plasma concentrations of FgDP were positively correlated with FbDP (r = 0.667, P less than 0.001). When analysed according to the disease categories, the magnitude of elevations of FbDP and FgDP was most prominent in venous thrombotic disease such as deep vein thrombosis and pulmonary embolism. These findings indicate that fibrinolysis is accelerated in patients with thrombotic disease and that fibrinolysis is frequently accompanied by some fibrinogenolysis in these patients. PMID- 1606292 TI - Comparison of fibrin-mediated stimulation of plasminogen activation by tissue type plasminogen activator (t-PA) and fibrin-dependent enhancement of amidolytic activity of t-PA. AB - Studies in the past 10 years have shown that there are two different, but related pathways for the acceleration of tissue-type plasminogen activator (t-PA) catalysis: (1) fibrin-dependent enhancement of t-PA amidolytic activity by fibrin binding; (2) fibrin-mediated stimulation of plasminogen activation by t-PA via the formation of a ternary complex of fibrin, t-PA and plasminogen. The common characteristic of both phenomena is the affinity of t-PA for fibrin, which is realized by the same enzyme binding site. However, a comparison of the kinetic data, the participating fibrin structures and the differences between single chain and two-chain t-PA (sct-PA and tct-PA, respectively) shows that both phenomena have different causes. Fibrin-mediated stimulation of plasminogen activation involves both sct-PA and tct-PA and different fibrinogen derivatives such as fibrin, fibrinogen cyanogen bromide fragment FCB-2, fibrin alpha-chain and poly-lysine. This mechanism is described by a marked apparent decrease in the KM value. In contrast, fibrin-dependent enhancement of t-PA activity against low molecular weight peptides is exclusive to sct-PA and is characterized by an increase in the kcat value and, depending on the nature of the substrate, by an increase in kcat and a decrease in KM. Thus, sct-PA activity modulation depends strictly on the correct three-dimensional folding of fibrin and is not mediated by fibrinogen fragment FCB-2 or isolated fibrin chains.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606293 TI - Recommendations on choice of therapeutic products for the treatment of patients with haemophilia A, haemophilia B and von Willebrand's disease. UK Regional Haemophilia Centre Directors Committee. PMID- 1606294 TI - Molecular link between membrane cholesterol and cyclic nucleotides in human platelets. AB - Because of the unresolved complex role of membrane cholesterol content in platelet activity, the present study was addressed to understand two specific issues; firstly whether variation in membrane cholesterol content could influence cyclic nucleotide levels within platelets, and secondly whether the membrane cholesterol modulated cyclic nucleotide levels were mediated through phospholipase A2 activation. The results of this in vitro study revealed that membrane cholesterol not only had the inherent capacity to induce changes in the levels of cyclic nucleotides within human platelets but also that this effect was mediated through its ability to modulate phospholipase A2 activity. Based on these results we suggest that membrane cholesterol modulated phospholipase A2 activity may be the molecular link between the membrane cholesterol content and cyclic nucleotides within human platelets. PMID- 1606295 TI - [Importance of physical parameters for the effectiveness of radiofrequency catheter ablation]. AB - Radiofrequency catheter ablation has been shown to be an effective form of treatment of accessory pathways in patients with WPW-syndrome and other supraventricular tachycardias. However, the biophysical parameters so far used in vivo neither correlated with the size of the myocardial lesion nor did they provide any information about contact of the electrode with the myocardial wall. In this study, 104 radiofrequency energy applications were performed on excised pig myocardium in circulating heparinized pig blood, and in blood alone, and root mean square (rms) voltage, current and phase angle were measured using a specially developed device. The calculated effective power and output power differed by only 2-7% measured at the point of maximum current during coagulation. A progressive drop in current following a rise in impedance led to a phase shift of more than 80 degrees with a decrease in effective power to 17% of the output power. Hence, apparent output power was mainly ineffective power. The time-dependent variations of phase angle, impedance and current were found to be useful for distinguishing between the coagulated media. These results show that physical parameters measured during radio-frequency catheter ablation may help to monitor electrode position in the clinical situation and reduce the number of ineffective energy applications. PMID- 1606296 TI - [Improved learning capacity and discrimination performance of neural networks in pattern recognition of biosignals]. AB - Pattern recognition was an important goal in the early work on artificial neural networks. Without arousing dramatic speculation, the paper describes, how a "natural" method of dealing with the configuration of the input layer can considerably improve learning behaviour and classification rate of a modified multi-layered perception with backpropagation of the error learning rule. Using this method, recognition of complex patterns in electrophysiological signals can be performed more accurately, without rules or complicated heuristic procedures. The proposed technique is demonstrated using recognition of the J-point in the ECG as an example. PMID- 1606297 TI - [Movement analysis with microgravitation: theory and practical aspects for the calculation of target movements with the MONIMIR helmet lamp]. AB - A new optoelectronic system for movement analysis is introduced. This equipment was employed with success during an Austrian-Soviet space flight. The method for the determination of position and orientation is described with the aid of an example, namely the determination of the location of the intersection of a beam of light generated by a helmet-mounted lamp with a screen. PMID- 1606298 TI - [A method for in vivo measurements of implants used in the reconstruction of spinal fractures]. AB - Little is known about the forces and moments acting on the spinal column during various movements and activities, and thus about the loading of implants used in the treatment of spinal fractures. A measuring method using an external fixation device was developed to determine the in vivo loading of spinal implants. On the basis of these data the forces acting on the spine can be calculated. The present paper describes this measuring method as applied to the fixation device, and initial experience with this device in a first application is presented. PMID- 1606299 TI - Pediatric AIDS and perinatal HIV infection in Zaire: epidemiologic and pathologic findings. AB - HIV infection in women and children is a special problem in Zaire and in other countries where heterosexual transmission is predominant. Nearly half of the cases of HIV infection are in women 15 to 30 years old and as many as seven infected infants may be born each year. Whether or not infected at birth, these children have mothers, and often fathers, who are infected and likely to die while they are still very young. Such orphaned children, as well as those whose families cannot provide adequate food and health care, add to the problematic economies of developing countries. The problems of children of HIV-infected mothers in developing countries may be compounded further by factors directly related to their mother's disease. Infected mothers who are sick may produce insufficient levels of antibodies and be unable to provide their children with adequate natural passive immunity before birth. Their infants may also receive inadequate levels of breast-milk-derived antibodies possibly enhancing their already increased susceptibility to perinatal infections, and lastly, the volume of breast milk produced by these mothers may be inadequate for the nutrition of these infants. All these factors may further compromise the already difficult task of distinguishing those infants of HIV-infected mothers who are ill because they are infected from those who are ill because of their mother's disease. Regardless of the mechanisms accounting for the increased vulnerability of infants of HIV--seropositive and AIDS-afflicted mothers to perinatal infections, infant mortality can be expected to increase significantly as a direct consequence of the progression of the HIV pandemic throughout Africa and possibly other developing countries; this in populations already with a total under five years-of-age mortality rate exceeding 15%. The association of chorioamnionitis with HIV seropositivity and with the clinical status of the mother seems to suggest that impaired maternal immunity increases the risk of premature birth, its consequent lower birth weight, and to HIV or other perinatally acquired infections. The identification of women at higher risk of chorioamnionitis and their treatment might provide a means to decrease the risk of premature delivery and possibly reduce the rate of HIV transmission to their infants. The pathologic changes in organs of infants and children with HIV infection require in-depth, systematic study to better define the natural history of perinatal HIV disease and infection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606300 TI - Symptomatic human immunodeficiency virus infection in children in Puerto Rico. The University Pediatric Hospital experience. PMID- 1606301 TI - Epidemiology of HIV infection and AIDS in childbearing women in the United States. AB - HIV infection and AIDS is of increasing prevalence among women in the United States, as documented by the AIDS surveillance data and HIV-seroprevalence data from pregnant women and parturients. Monitoring epidemiologic trends in childbearing women has required clever and creative strategies like those of Hoff et al. The impact on women in the reproductive years, on the reproductive health of these women, and on the outcome of their pregnancies is of substantial concern. The effect of HIV infection on pregnancy and of pregnancy on HIV infection must be clarified but suggests that monitoring T cell levels in pregnancy may be of benefit in identifying women at risk of serious infections. Treatment of HIV-infected women with antiretroviral and other therapies may happen in the future not only to treat the mother but also to investigate the prevention of in utero transmission. In the meantime, studies of the natural history of HIV infection in HIV-infected pregnant women are necessary to clarify when, by what mechanism, and how to prevent in utero transmission of infection from mother to fetus. The committee on AIDS Research and the Behavioral, Social and Statistical Sciences of the National Research Council is optimistic that "the statistics derived from the survey of childbearing women in the United States will provide a basis both for projecting future AIDS cases among infants and, perhaps most importantly, for monitoring the prevalence of infection among an important part of the population of heterosexually active women." The epidemic of HIV in men, women, and children will be controlled not only by finding effective treatments but also by developing strategies that prevent the spread of infection from one person to another. As Quinn et al. stated in a recent editorial, "The rate of increase will be influenced markedly by our degree of success in preventing the sexual, parenteral and perinatal transmission of HIV.... Without immediate action, the spread of HIV and related retroviruses is likely to escalate throughout our hemisphere and to have a profound impact on the medical, cultural, economic and political structure of the Americas." PMID- 1606302 TI - Pathology of the placenta in HIV-1 infection. PMID- 1606303 TI - Manufacturing process, resultant risk profiles and their control in the production of nickel-cadmium (alkaline) batteries. PMID- 1606304 TI - A case of methyl bromide poisoning. AB - A case of methyl bromide poisoning in a nurseryman is described. This case demonstrates the insidious nature and delayed action of the gas and the lengthy recovery period following poisoning and persistence of neurological signs and symptoms. PMID- 1606305 TI - Occupational medicine and the EC. PMID- 1606307 TI - The business of safety. PMID- 1606306 TI - Sickness, absence and physiotherapy. PMID- 1606308 TI - Screening for job placement: an in-house placement screening programme. AB - A system of screening for all types of job placement has recently been introduced at British Airways, following consultation with all interested parties. The rationale, development and practical aspects are described. PMID- 1606309 TI - Health and lifestyle of general practitioners and teachers. AB - General practitioners (408) and secondary teachers (385) responded to a questionnaire about their health and lifestyle with a response rate of 48 and 45 per cent respectively. Their answers were corroborated by a separate questionnaire completed by their spouse or domestic partner. A sub-group of 50 general practitioners and 50 teachers were examined to assess their physical fitness and mental health. Half of each group was below average fitness compared to the general population. General practitioners were more likely than teachers to practise disease prevention. Ten per cent of general practitioners and 13 per cent of teachers were smokers; 8 per cent of general practitioners and 14 per cent of teachers reported an alcohol consumption that exceeded recommended limits. General practitioners took remarkably little sickness absence compared to teachers. Symptoms of anxiety and depression were more common in teachers: a need for alcohol, binge eating and sleep difficulties were frequently experienced in both groups. Medication taken by the two groups was similar and self-medication was common amongst the general practitioners. Less than half the general practitioners thought they would use an occupational health service if it were established. PMID- 1606310 TI - Should prospective NHS employees have routine blood counts? AB - The results of pre-employment haematological screening from 958 prospective National Health Service (NHS) workers were reviewed. Although many abnormalities were found, few were judged to be clinically significant. In only one case did the examination affect employment. Haematological screening is an unnecessary part of the pre-employment medical assessment of prospective NHS employees. PMID- 1606311 TI - Formaldehyde. AB - In 1979 formaldehyde was projected into the toxicological limelight when Kerns and his group from the American Chemical Industry Institute of Toxicology (CIIT) released preliminary results of an inhalation study on male and female rats. Those animals exposed to 14.3 p.p.m. for 8 h/day and 5 days/week for up to 2 years showed the development of squamous cell carcinomas in a high proportion (55 per cent) of the animals. Rats similarly exposed to 5.6 p.p.m. were slightly affected with 0.85 per cent producing tumours. The next 10 years became a frenzy of activity by toxicologists, epidemiologists and industry groups, all striving to answer the question: 'Is formaldehyde a human carcinogen?'. This paper will attempt to examine the extent to which the question has been answered. It will consider how the industry responded to the initial shock finding and review the subsequent accumulation of animal and human data. It will also address the regulatory position and compare the steps taken in different countries to control the risk, and again consider how industry has responded to such regulatory forces. This review will necessarily only be able to cover the main issues and major conclusions as the extent of the subject is enormous. There are, however, a number of comprehensive texts on the subject should more information be required. PMID- 1606312 TI - Health and lifestyle characteristics of professional singers and instrumentalists. AB - Ninety-one instrumentalists and 51 opera singers of the Royal Theatre in Copenhagen, Denmark, were examined, in order to study the frequency of symptoms from the musculoskeletal system and upper airways. The response rate was 91 per cent. Estimates of odds ratios (OR) with 95 per cent confidence interval were calculated, using multiple logistic regression equations, adjusting for age and gender. The frequency of musculoskeletal complaints was the same in singers and instrumentalists. Musculoskeletal problems were however not identical. Instrumentalists had statistically significantly more symptoms from the arm region than singers, OR = 3.1 (1.02-9.5), P less than 0.05. In contrast, instrumentalists had significantly fewer complaints from hip-, knee- and foot joints than singers, OR = 0.2 (0.07-0.61), P less than 0.001. Singers had significantly more symptoms from mouth, lips or throat than instrumentalists, OR = 4.5 (1.7-11.5), P = 0.002. Both male and female instrumentalists had a higher blood pressure. This difference seemed at least in part to be explained by a higher alcohol intake among instrumentalists. We suggest these differences in life style and health characteristics are likely to be caused by professional, ie occupational, work loads. PMID- 1606313 TI - Wet-bulb globe temperature index: a predictor of physiological strain in hot environments. AB - The readings of the natural wet-bulb (tnwb) and globe thermometer for computing Twbg index (indoors) were taken between 08.00 to 17.00 h at two-hour intervals in different work locations in the glass bangle and brassware industries. For assessing the physiological reliability of the Twbg index for heat stress, the radial pulse rate was monitored at two-hour intervals in 60 brassware workers and 77 glass bangle workers (mean ages: 25.3 +/- 8.8 and 28.1 +/- 5.7 years) belonging to various occupations exposed to thermal radiation for 9.3 +/- 8.5 and 11.2 +/- 4.8 years respectively. The mean values of Twbg index observed in the brassware and glass bangle industries were found to be almost of the same order (34.4 +/- 3.0 degrees C and 35.2 +/- 1.1 degrees C). The radiant heat seemed to make the most significant contribution to the environmental heat stress in these industries. The globe temperature near the main melting furnace was as high as 53.8 +/- 3.0 degrees C and 59.2 +/- 4.02 0C in the glass bangle and brassware industries respectively. It was, therefore, expected that the exposed workers would show pronounced physiological strain. Surprisingly the pulse rates of these workers did not indicate any significant physiological strain since the maximal pulse rates recorded did not exceed the safe limits of circulatory strain recommended by the WHO.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606314 TI - Pinealocyte synaptic ribbons and neuroendocrine function. AB - A comparative study of pinealocyte synaptic ribbons (SR) revealed two predominant populations exhibiting either a rod/ribbon shape (SRr) or a spherical/punctate shape (SRsp). Species-specific differences were found in the abundance of SR, the ratio of SRr/SRsp, and the occurrence of SR in ribbon fields. The close topographical relationship of SR to the plasma membrane and the numerical changes that occurred with changes in metabolism of the pinealocytes suggest that SR have important vesicle-mediated interactions with the cell membrane. Experiments designed to clarify the relationship between SR and pineal neuroendocrine function revealed a positive correlation between SR numbers and indole intermediates during pineal development in the rat, and increased SR frequency after denervation of the rat pineal gland or administration of the beta adrenergic agonist, isoproterenol. These data are consistent with the hypothesis that SR function is linked to receptor mechanisms regulating indoleamine production in the pineal gland. PMID- 1606315 TI - Fine structure of the pinealopetal innervation of the mammalian pineal gland. AB - The mammalian pineal gland is innervated by peripheral sympathetic and parasympathetic nerve fibers as well as by nerve fibers originating in the central nervous system (central innervation). The perikarya of the sympathetic fibers are located in the superior cervical ganglia, while the fibers terminate in boutons containing small granular vesicles and a few large granular vesicles. Both noradrenaline and neuropeptide Y are contained in these neurons. The parasympathetic fibers originate from perikarya in the pterygopalatine ganglia. The neuropeptides, vasoactive intestinal peptide and peptide histidine isoleucine, are present in these fibers, the boutons of which contain small clear transmitter vesicles and larger granular vesicles. The fibers of the central innervation originate predominantly from perikarya located in hypothalamic and limbic forebrain structures as well as from perikarya in the optic system. These fibers terminate in boutons containing small clear and, in certain fibers, an abundant number of large granular vesicles. In rodents, the majority of the central fibers terminate in the deep pineal gland and the pineal stalk. From these areas impulses might be transmitted further caudally to the superficial pineal gland via neuronal structures or processes from pinealocytes. Several hypothalamic neuropeptides and monoamines might be contained in the central fibers. The intrapineal nerve fibers are located both in the perivascular spaces and intraparenchymally. The majority of the intraparenchymally located fibers terminate freely between the pinealocytes. However, some nerve terminals make synaptic contacts with the pinealocytes and in some species with intrapineal neurons. In fetal mammals, sympathetic, parasympathetic, and central fibers are also present. In addition, an unpaired nerve, connecting the caudal part of the pineal gland with the extreme rostral part of the mesencephalon, is present. This nerve is a homologue to the pineal nerve (nervus pinealis) observed in lower vertebrates. PMID- 1606316 TI - Third ventricular pineal gland grafts in the gerbil: an electron microscopical and immunohistochemical investigation. AB - The superficial pineal gland was grafted into the third ventricle of adult Mongolian gerbils. Donor pineal glands from both neonatal and 3-4 week old gerbils were able to survive for at least 6 months. The pinealocytes of the grafted superficial pineal glands maintained the morphology and the S-antigen immunoreactivity of the in situ pineal complex. Synaptic ribbons and spherules were present but rare. Unlike the in situ pinealocytes, glycogen accumulations were common in the graft pinealocytes. Site specific modulation of structure was indicated as the ventricular surface of the grafts became covered with cerebrospinal fluid (CSF)-contacting pinealocytes typical of those seen in the deep pineal. The CSF-contacting pinealocytes of the graft had numerous processes that extended along the ventricular surface of the graft. The blood vessels of the grafts had non-fenestrated endothelium and wide perivascular areas typical of those seen in the in situ pineal complex. Tyrosine hydroxylase-immunopositive nerve fibers were present in the grafted tissue indicating reinnervation of the graft. The source of the fibers was not determined. The nerve fibers were present both within the perivascular area and within the parenchyma where they were associated with pinealocytes. The results demonstrate that the cerebral ventricles are an ideal location for the survival of superficial pineal gland grafts. It is suggested that pineal grafts may be a means to further study pineal development and innervation. PMID- 1606317 TI - The embryonic pineal body as a multipotent organ. AB - The repertoire of differentiating potency of mammalian and avian pineal cells has been examined utilizing cell culture technique. Skeletal muscle fibers are differentiated from pineal cells of the rat under the usual culture condition and from those of quail under hypertonic conditions. Myogenesis of pineal cells may be explained from the ontogeny of the pineal body. Anlagen of a pineal body are situated in bilateral cephalic neural folds, which also supply multipotent neural crest cells. In some conditions, almost all quail pineal cells are able to differentiate into pigmented epithelial cells and/or lens cells. Opsin containing cells found in culture of rat pineal cells may be in a similar category reflecting the "third eye": the phylogenetic ancestor of the pineal body of avian and mammalian species. Neuron-like cells have also been reported and neuronal morphology has been intensified under the effect of testicular hyaluronidase. The cytodifferentiation described above is suggested to be different expressions of a single type of progenitor cells in the pineal body. In relation to multipotentiality of pineal cells, the original differentiating state of pineal cells is interesting; it has been found that tyrosinase is expressed from the beginning of pineal formation and that its expression is stage-specific (during embryonic period) and site-specific (predominance in the dorsal half of the pineal body and in the apical cytoplasm of the pineal cell). In the 8 day quail embryo used for culture studies, three differentiating states as to tyrosinase are noticed. However, the distinction may be apparent, as even the cells negative in tyrosinase in this stage are still ready to express tyrosinase in the suitable culture condition.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606318 TI - Ultrastructural morphology and allergen detection in birch pollen after aqueous, anhydrous-liquid, and vapor fixation techniques. AB - In order to find a good compromise between preservation of ultrastructural morphology and retention of antigenicity, birch pollen grains were chemically fixed in aqueous p-formaldehyde or glutaraldehyde, in p-formaldehyde or glutaraldehyde dissolved in anhydrous glycerol, and in p-formaldehyde or glutaraldehyde vapor. Representative cytoplasmic areas were inspected for the preservation of ultrastructural morphology and for their capacity to bind a monoclonal antibody against Bet v I, the major birch pollen allergen. The experiments showed that cytoplasmic morphology was best preserved after vapor fixation in p-formaldehyde. This fixation also led to the highest degree of specific antibody binding. PMID- 1606319 TI - Comparison of nuclear hydration in boar spermatozoa before and after freeze thawing: contrast analysis of cells embedded in bromide-labeled medium. AB - Epon labeled with bromide was used to embed ejaculated and freeze-thawed spermatozoa, with the hypothesis that it replaces most of cell water. Image analysis of relative contrasts between sperm nuclei and the surrounding medium revealed that when used in low concentrations, bromide is mostly adsorbed to the nuclear structures. For higher concentrations, the chromatin is saturated, and the increase in contrast can be used to calculate relative differences in the hydration of nuclei. Boar sperm nuclei are more hydrated after freeze-thawing than before. PMID- 1606321 TI - First demonstration of anesthesia at the Massachusetts General Hospital. PMID- 1606320 TI - Panic disorders: introduction. PMID- 1606322 TI - Anxiety disorders: an overview. AB - As a group, anxiety disorders are the most prevalent class of mental disorders. Over the course of a lifetime, 15% of the population experience one or another anxiety disorder. PMID- 1606323 TI - Treatment of panic disorder. PMID- 1606324 TI - Panic disorder: a clinical perspective on acute treatment and future research needs. AB - Panic disorder is a common disorder for which there are highly effective treatments. Patients usually present for treatment in acute distress and initially have difficulty responding to cognitive behavioral therapies. In contrast there is a high response rate to pharmacologic treatments. Cognitive behavioral techniques can be helpful in facilitating the taper and eventual discontinuation of medication and may play a role in preventing relapse. The disorder appears to have a chronic course requiring maintenance medication for at least six months. Phobic avoidance appears to be primarily a learned response and is best treated with in vivo desensitization. PMID- 1606325 TI - Medical aspects of panic disorder. AB - Panic attacks may be due to one or more of a large number of underlying physical or psychiatric disorders. Only when these possible etiologies have been excluded may the diagnosis of panic disorder be established. PMID- 1606326 TI - Panic disorder in children and adolescents. AB - Undiagnosed panic disorder may be a significant health problem in children and adolescents. Some of the adolescents and children who have presented for years with school refusal or psychogenic somatic complaints may suffer from this disorder and may benefit significantly from appropriate treatment. PMID- 1606327 TI - Comorbidity of panic disorder and substance use disorders. PMID- 1606328 TI - Workplace smoking policies of Rhode Island employers. PMID- 1606329 TI - Involvement in medical informatics may enable pharmacists to expand their consultation potential and improve the quality of healthcare. AB - The outlook for pharmacy-related services foretells more involvement of both computers and information systems. Expert therapeutic systems and databases will enable pharmacists to expand their consultation potential through networks and improve the quality of healthcare that they provide. Therapeutic information management could be the largest pharmacy specialty of the future. As knowledge based systems and networks become commonplace, there will be an increasing need for new components, system monitoring, and quality assurance. This is an opportunity for pharmacy to bring medical computing, as it relates to therapeutics, into the mainstream of the profession as a new discipline. PMID- 1606330 TI - Computers in healthcare: overview and bibliography. AB - OBJECTIVE: The objective of this article is to provide an overview of computer technology and an associated bibliography, emphasizing institutional-based healthcare applications and pharmacoinformatics. DATA SOURCES: References were selected from the authors' files and from a computerized search over the last five years on computers in healthcare/medical informatics and in pharmacy. STUDY SELECTION: Articles selected for review and discussion were considered to be important contributions to the respective areas listed in the bibliography and representative of advancements in computer applications in healthcare and pharmacy. DATA SYNTHESIS: The computer has become an important support tool for healthcare professionals. Medical informatics and the discipline related to pharmacy, called pharmacoinformatics, have evolved from the cognitive underpinnings of medicine, pharmacy, and computer science. Recent developments in computer technology have resulted in computers that are fast, increasingly portable, and user friendly. Hospital information systems employ computers in various ways to deal with the vast amount of information used by various departments. Standards for electronic data exchange are being developed to increase the integration potential of these systems. Hospital pharmacists have used computers for drug distribution, financial analysis and inventory control, drug interaction detection, pharmacokinetic dosing, drug information, and drug therapy monitoring. Expert systems are being developed in several areas of drug therapy. Pharmacy educators have developed interactive courseware to help students learn problem-solving skills in the areas of calculations, therapeutics, and drug information. CONCLUSIONS: Pharmacists need to become more involved with applications of technology to pharmacy. Properly implemented, computers can provide more time for pharmacists to use their cognitive skills in the delivery of pharmaceutical care. PMID- 1606332 TI - Origins of the Annals of Pharmacotherapy and a tribute to its founder. PMID- 1606331 TI - Effect of the addition of ciprofloxacin on theophylline pharmacokinetics in subjects inhibited by cimetidine. AB - OBJECTIVE: Although the effect of individual enzyme inhibitors on hepatic microsomal enzyme activity has been studied extensively, little data exist on the effects of combinations of inhibiting agents. The purpose of this study was to investigate the effect of the addition of a second hepatic oxidative enzyme inhibitor on the inhibition of metabolism in subjects already maximally inhibited by cimetidine. Ciprofloxacin was used as the second inhibitor. DESIGN: In a randomized crossover sequence, subjects received theophylline 5 mg/kg on day 6 of therapy with cimetidine 2400 mg/d, ciprofloxacin 1 g/d, both drugs, or while drug free. SETTING: National Institutes of Health-funded General Clinical Research Center. PARTICIPANTS: Eight normal volunteers (6 men, 2 women; mean age 25.2 y). OUTCOME MEASURES: Theophylline pharmacokinetic parameters after each treatment were determined by model independent pharmacokinetic analysis. Statistical analysis of the data for differences between treatments was assessed by ANOVA for repeated measures. RESEARCH: When administered alone, ciprofloxacin and cimetidine caused a significant increase in theophylline elimination half-life and a decrease in clearance. Theophylline elimination half-life was significantly longer during combined therapy compared with either drug alone. Theophylline clearance was lower during combined treatment, although this relationship did not reach statistical significance. CONCLUSIONS: The addition of a second enzyme inhibitor in subjects receiving maximally inhibiting doses of cimetidine can produce a further decrease in the hepatic metabolism of drugs that are metabolized by the cytochrome P-450 microsomal enzyme system. As cimetidine and ciprofloxacin are frequently used together for a variety of common clinical indications, clinicians should be aware of this drug interaction and should consider that a similar effect may occur when other enzyme inhibitors are used concomitantly. PMID- 1606333 TI - Pharmacogenetics: Part I. PMID- 1606334 TI - Moricizine-warfarin: a possible drug interaction. PMID- 1606335 TI - Intravenous aminophylline: in vitro stability in fat-containing TPN. PMID- 1606336 TI - "Reverse placebo effects": anticipation/anxiety at the possibility of receiving placebos. PMID- 1606337 TI - Effect of the mode of lipid administration on parenteral nutrition-related infections. AB - OBJECTIVE: To determine if total nutrient admixtures (TNAs) influence the rate of infection in clinical practice. DESIGN: Prospective, randomized trial. SETTING: Department of Veterans Affairs Medical Center. PATIENTS: All patients were administered parenteral nutrition (PN) via a central venous catheter and received daily lipids. INTERVENTION: Patients were randomized as to the mode of administration of lipids. Lipids were either administered with other PN components in a TNA or were piggybacked (PB) into the PN solution. MAIN OUTCOME MEASURES: Treatment groups were compared for the rate of occurrence of PN-related infections. Infections were classified as catheter infections or catheter sepsis. RESULTS: Ninety-eight patients were entered into the trial. Data from 96 patients (44 TNA, 52 PB) were available for analysis. Treatment groups were well matched for age, baseline albumin, days of PN, predicted basal metabolic rate, and calorie and protein requirements. TNA patients received a significantly greater percentage of nonprotein calories as lipid. The incidence of infection was 12.6 and 10.3 per 1000 days of PN in the TNA and PB groups, respectively (p = 0.89). The microorganisms responsible for infection and the type of infections that developed were similar in both groups. CONCLUSIONS: Use of TNAs does not influence the rate of infection in patients receiving PN. PMID- 1606338 TI - Treatment of valproic acid-associated hepatic failure with orthotopic liver transplantation. AB - OBJECTIVE: To report a case of valproic acid (VPA)-induced hepatotoxicity and to discuss the incidence rates, risk factors, possible etiologies, preventive measures, and treatment courses for this severe reaction. DATA SOURCES: Case reports, review articles, and relevant laboratory studies identified by MEDLINE. DATA EXTRACTION: Data were abstracted from pertinent published sources by one author and reviewed by the remaining authors. DATA SYNTHESIS: The case of a 23 year-old woman with VPA-associated hepatic failure was successfully treated with orthotopic liver transplantation. Hepatic failure is a rare, often fatal, adverse effect of VPA. Most cases of VPA-associated hepatic failure have occurred within several months of initiation of therapy. Initial symptoms of presentation often include nausea and vomiting, lethargy, or loss of seizure control. Laboratory values to be monitored include serum concentrations of hepatic enzymes, and, in some patients, tests indicative of the liver's synthetic capabilities. The exact mechanism of VPA-associated hepatic failure has not been clearly established; however, it is postulated to involve the formation of toxic metabolites. Major risk factors include age less than two years and concomitant treatment with more than one anticonvulsant. Other significant risk factors include underlying metabolic or serious neurologic disorders. CONCLUSIONS: Caution should be taken when initiating VPA therapy and clinicians should be familiar with the risk factors and clinical presentation of this reaction. PMID- 1606339 TI - Anaphylactoid reaction to intravenous acetylcysteine associated with electrocardiographic abnormalities. AB - OBJECTIVE: To review the potential for anaphylactoid reactions to intravenously administered acetylcysteine when used in the treatment of acetaminophen overdose. This case is unique in that electrocardiographic changes, including ST segment depression and T-wave inversion were associated with the episode and complicated the diagnosis. DATA SOURCES: Reference articles and letters are identified in the text. DATA SYNTHESIS: Intravenous administration of acetylcysteine has been used in the treatment of acetaminophen overdose. This route may be considered in some clinical situations where oral therapy is complicated. Anaphylactoid reactions, including cutaneous eruptions, flushing, chest pain, tachycardia, and fever have been reported in up to three percent of patients receiving intravenous acetylcysteine. The nature of these reactions and evidence concerning their etiology suggest a histamine-release phenomenon. Response to intervention with antihistamines and the safety of further acetylcysteine administration are discussed. CONCLUSIONS: This case illustrates a variant anaphylactoid reaction to intravenously administered acetylcysteine and emphasizes the need for practitioners to consider the potential for these reactions prior to initiation of therapy and indicates appropriate treatment of these reactions. PMID- 1606340 TI - Populations at risk for penicillin-induced seizures. AB - OBJECTIVE: This article reviews principles associated with penicillin's epileptogenic activity in an effort to alert clinicians of patients at high risk for penicillin-induced seizures. The case presentation exemplifies the most prevalent factor predisposing patients to penicillin-induced seizures--renal impairment. DATA SOURCES: References are identified from pertinent articles and books. DATA SYNTHESIS: The epileptogenic properties of penicillin are explained on the basis of the beta-lactam ring's binding to gamma aminobutyric acid receptors. Several patient populations are at risk for potentially fatal neurotoxic symptoms. Most of these patients demonstrate impaired renal function, either as the primary condition or secondary to an infectious process. The other at-risk populations include infants and the elderly, patients with meningitis, patients undergoing intraventricular antibiotic therapy, and patients with a history of seizures. Treatment remains controversial; however, benzodiazepines theoretically produce a favorable response. CONCLUSIONS: Pharmacokinetic parameters explain patient populations most at risk; a guideline equation has been recommended to allow clinicians to make appropriate dose adjustments based on creatinine clearance. Physicians and pharmacists must recognize the populations most at risk for high-dose, penicillin-induced neurotoxicities; monitor these patients at least during the first 72 hours, and reduce or discontinue therapy when appropriate. PMID- 1606341 TI - Generalized seizures secondary to high-dose busulfan therapy. AB - Two patients without prior histories of neurologic disorders experienced generalized seizures while receiving high-dose busulfan (total dose 16 mg/kg) as part of a preparative regimen for allogeneic bone marrow transplantation. A review of the literature revealed 14 similar occurrences. Maintenance of therapeutic blood concentrations of phenytoin in subsequent patients at our institution has resulted in no further patients experiencing generalized seizures. Prophylactic anticonvulsant therapy should be considered in patients receiving high doses of busulfan. PMID- 1606342 TI - High-dose intravenous immune globulin in the management of severe Guillain-Barre syndrome. AB - OBJECTIVE: To evaluate the efficacy of high-dose intravenous gammaglobulin (IGIV) versus plasmapheresis in patients with severe Guillain-Barre syndrome (GBS) and compare the costs of both treatments. DESIGN: Retrospective review of all severely disabled GBS patients admitted between January 1 and December 31, 1990. SETTING: Neurologic unit of a tertiary-care center. PATIENTS: Six patients fulfilling the criteria for the diagnosis of GBS agreed upon by the ad hoc National Institute of Neurological and Communicative Disorders and Stroke committee. INTERVENTION: Four patients treated with plasmapheresis underwent three to six sessions of plasma exchange. Two patients received IGIV 0.4 g/kg/d administered over a five-day period. MAIN OUTCOME MEASURES: Recovery time, functional assessment (performed according to the grading scale used in the North American trial) at 30, 60, and 90 days after treatment. Cost of plasmapheresis, IGIV, and bed/day were compared. RESULTS: Clinical recovery appeared to be faster and more complete in the IGIV group than in the plasmapheresis group. No adverse reactions related to IGIV treatment appeared. The total cost was greater in the plasmapheresis group. CONCLUSIONS: These preliminary results suggest that IGIV may be more beneficial and less expensive than plasmapheresis in treatment of GBS. Definitive conclusions regarding the efficacy of IGIV in GBS will need to await the final analysis of the Ducht randomized multicenter trial comparing IGIV with plasmapheresis. PMID- 1606343 TI - Toxic epidermal necrolysis possibly linked to aztreonam in bone marrow transplant patients. AB - OBJECTIVE AND SETTING: After instituting aztreonam as part of antibiotic prophylaxis in bone marrow transplant (BMT) patients at the Seattle Department of Veterans Affairs Medical Center, the first two cases of toxic epidermal necrolysis (TEN) occurred in more than 250 BMT patients at this center. We have examined the possible cause-and-effect relationship between aztreonam and TEN. PATIENTS: The first patient was a 23-year-old man with acute lymphocytic leukemia receiving a BMT from a related mismatched donor. He experienced profound conjunctivitis and superficial bulla covering 60 percent of his body surface area (BSA). The second patient, a 32-year-old man with lymphoma, received a BMT from a matched unrelated donor. He exhibited lymphocytosis, acute conjunctivitis, and bullous lesions covering 60 percent of his BSA. INTERVENTIONS: Aztreonam was discontinued in both patients. The first patient was treated with pigskin grafting and the second was treated with topical silver sulfadiazine. RESULTS: Despite stabilization of symptoms, both patients eventually died of infectious complications. CONCLUSIONS: Histological data in both patients were more consistent with TEN than graft-versus-host disease (GVHD) in that dermal infiltrates were sparse or absent. The onset of cutaneous symptoms was of more acute onset than acute GVHD, and ocular complaints are uncommon in acute GVHD. Furthermore, the onset of TEN bore a closer temporal relationship to aztreonam than to other drugs administered. PMID- 1606344 TI - Clonidine in attention deficit hyperactivity disorder. PMID- 1606345 TI - Propranolol in variceal hemorrhage. PMID- 1606346 TI - Nephrotoxicity of contrast media following cardiac angiography: pathogenesis, clinical course, and preventive measures, including the role of low-osmolality contrast media. AB - OBJECTIVE: To review the incidence, definition, clinical course, risk factors, pathogenesis and prevention of contrast-associated nephropathy (CAN) following cardiac angiography with emphasis on differences between high-osmolality contrast media (HOCM) and low-osmolality contrast media (LOCM). DATA SOURCES: Investigations in animal models and in patients following cardiac angiography. DATA EXTRACTION: Animal models of the pathogenesis of CAN are presented. Human studies describing the incidence, clinical course, risk factors, and prevention of CAN are reviewed. Comparative clinical trials of HOCM (diatrizoate, metrizoate) and LOCM (iohexol, iopamidol, ioxaglate) nephrotoxicity following cardiac angiography are critically evaluated. DATA SYNTHESIS: All clinical studies comparing CAN of HOCM versus LOCM following cardiac angiography have some methodologic limitations (e.g., small sample size, lack of control for other factors) that may affect renal function, lack of stratification for other reported risk factors, and variable or short follow-up periods. CONCLUSIONS: Whether the incidence of CAN following cardiac angiography is reduced with LOCM remains controversial. The incidence of CAN in patients with normal renal function does not appear to differ in patients treated with LOCM versus HOCM because few patients in each group develop renal failure. Additional controlled clinical trials comparing CAN of LOCM and HOCM in patients with renal dysfunction are needed. Because of greater product cost and scarcity of documented benefit compared with HOCM, selection of LOCM based on the presence of renal dysfunction cannot be recommended at this time. PMID- 1606347 TI - "Brain attack": an indication for thrombolysis? AB - OBJECTIVE: The primary objective of this article is to introduce the reader to the use of thrombolytics in the acute treatment of ischemic stroke. Theory and experimental evidence to support this approach are emphasized in addition to potential adverse effects of thrombolysis. DATA SOURCES: A MEDLINE search was used to identify pertinent literature, including reviews. STUDY SELECTION: Studies were selected for detailed review if they involved stroke patients and addressed possible toxicities of therapy. Any abstracts concerning ongoing clinical trials also were reviewed. DATA EXTRACTION: Data from animal investigations using tissue plasminogen activator for the acute treatment of several models of cerebral ischemia were used to support the importance of early treatment (within six hours of symptom onset). Also, studies performed in animal models of stroke revealed that thrombolysis could be accomplished safely in acute ischemic stroke. All human studies published to data are anecdotal case reports, but point to the safety of thrombolysis if administered early. Reviews of ongoing multicenter trials are taken from published abstracts and proceedings. DATA SYNTHESIS: Thrombolysis holds promise as a hyperacute therapy for acute stroke; however, the risk of intracerebral hemorrhage remains. Crucial to the success of this and any other therapy for acute stroke is the ability to treat patients within hours of symptom onset. Also, the importance of concomitant medications such as heparin and aspirin has not yet been addressed. CONCLUSIONS: Pharmacists need to be knowledgeable of new treatments of stroke and the risks associated with them. As patient educators, pharmacists can contribute to public awareness by promoting the early recognition of stroke symptoms. As pharmacotherapists, pharmacists need to understand the risks and the important monitoring parameters related to thrombolysis. The results of ongoing multicenter clinical trials are awaited before making a final judgment on the usefulness of thrombolysis in acute ischemic stroke. PMID- 1606348 TI - Dose-ranging pharmacokinetic study of ciprofloxacin after 200-, 300-, and 400-mg intravenous doses. AB - OBJECTIVE: To assess the pharmacokinetics and tolerance of ciprofloxacin after the administration of single intravenous doses of 200, 300, and 400 mg. DESIGN: Double-blind, three-period, randomized, crossover trial. SETTING: Private, university-affiliated, hospital-based, clinical research center. PATIENTS: Normal healthy male volunteers, 18-40 years of age. INTERVENTIONS: Subjects received 200 , 300-, and 400-mg single intravenous doses of ciprofloxacin via 30-minute infusions in random sequence. MAIN OUTCOME MEASURES: Serum ciprofloxacin concentrations were determined by HPLC after each dose and the results were used to derive pharmacokinetic parameters. Tolerance was assessed by reported and observed adverse events, urine microscopic examinations for crystals, and examination of intravenous infusion sites. RESULTS: The mean area under the time curve (AUC) values displayed linearity with respect to the administered dose. No statistical differences were observed in total body clearance, steady-state volume of distribution, or elimination half-life with respect to dose administered. The mean total body clearance, steady-state volume of distribution, or elimination half-life ranged from 36 to 41 L/h, 146 to 169 L, and 3.5 to 3.7 h for the 200-, 300-, and 400-mg doses, respectively. Adverse effects, including venous irritation (four subjects) and crystalluria (two subjects), were mild and did not require withdrawal of any subject from the study. CONCLUSIONS: Intravenous ciprofloxacin in doses ranging from 200 to 400 mg demonstrated linear pharmacokinetics. These single doses were well tolerated, although cases of transient venous irritation and crystalluria were observed. PMID- 1606349 TI - Enhancing the pharmacist-computer interface. PMID- 1606350 TI - What is the clinical relevance of isolated systolic hypertension? PMID- 1606351 TI - Co-dergocrine mesylate. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in age-related cognitive decline. AB - Co-dergocrine mesylate is a combination of the mesylated forms of dihydroergocornine, dihydroergocristine, dihydro-alpha-ergocryptine and dihydro beta-ergocryptine. In animal models and healthy elderly volunteers the compound improves indices of cognitive function such as memory and learning. The mechanism(s) behind such action remains under investigation. Nonetheless, it has been proposed that co-dergocrine mesylate has a dual effect on central monoaminergic neurotransmitter systems, compensating for both hyperactivity and deficits of the adrenergic, serotoninergic and dopaminergic systems. The compound also appears to have a normalising effect on the power of electroencephalogram frequencies, and may improve cerebral metabolism. Results from controlled studies of elderly patients with age-related cognitive decline have established that co dergocrine mesylate is well tolerated and, in some studies, had statistically significant positive effects on symptoms of cognitive dysfunction. However, there is considerable controversy over the clinical relevance of these results as there was wide variability in the number and type of cognitive and neuropsychological assessments used in individual studies and there may have been considerable overlap in diagnosis of patients with varying degrees of dementia. In addition, the drug has not been compared with most other, more recently developed, centrally active agents. Thus, the specific place of co-dergocrine mesylate in the treatment of age-related cognitive decline remains undetermined, despite many years of clinical use. PMID- 1606353 TI - Diagnostic and therapeutic problems in prostatitis. Therapeutic position of ofloxacin. AB - Lower tract localisation studies have been the gold standard in diagnosing various kinds of prostatitis. Four clinical categories are recognised: acute and chronic bacterial prostatitis, nonbacterial prostatitis, and prostatodynia. In acute bacterial prostatitis Gram-negative bacteria are the most common pathogens isolated. The roles of Gram-positive bacteria in chronic bacterial prostatitis and of Chlamydia trachomatis in nonbacterial prostatitis are contentious. Treatment of these various forms of prostatitis has been a challenge to the clinician. The lack of penetration of various drugs into the prostatic tissue, because of poor lipid solubility, ionisation, protein binding, and unfavourable pH gradients from the plasma to the prostatic fluid, may be the main reasons for poor results. The minimum inhibitory concentration (MIC) of antibacterial drugs used, and the concentration of drugs actually obtained in the prostate, combined with the influence of pH and inoculum size, and the effect of prostatic fluid and prostatic extracts on MIC are important factors in determining at least the theoretical efficacy of various drugs in the treatment of prostatitis. The new fluoroquinolone ofloxacin, the first quinolone to be approved for the treatment of chronic bacterial prostatis, has excellent penetration into human prostate and high in vitro activity in human urine and prostatic tissue. From a theoretical standpoint, ofloxacin should be ideal in the treatment of chronic bacterial prostatis. Comparative studies have shown its superiority to carbenicillin. Several noncomparative studies have also been reported. The initial results are promising, but further investigations are needed. PMID- 1606352 TI - Sex steroids and cancer in older women. AB - Menopause and hormone replacement therapy (HRT) continue to be controversial subjects. The main concern is the potential risk of prolonged HRT and the possible development of endometrial and breast carcinoma. There is no obvious evidence at present to suggest that HRT increases endometrial carcinoma provided the patient receives progestogen for a period of 10 or more days (usual period is 12 days) during each month. However the breast does not seem to enjoy this safety margin and there is some concern about possible increase in the incidence of breast cancer if the treatment period is longer than 5 years. The increase in the risk is higher after 15 years of estrogen use. There is no obvious adverse effect on the ovary or on the cervix following HRT. PMID- 1606356 TI - The polypeptide part of human chorionic gonadotrophin affects the kinetics of alpha 6-sialylation of its N-linked glycans but does not alter the branch specificity of CMP-NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase. AB - Human chorionic gonadotrophin (hCG) is a heterodimeric glycoprotein hormone consisting of an alpha- and a beta-subunit, both containing two N-linked, complex type glycans. Using this hormone as a model glycoprotein, the influence of its polypeptide part on the activity and specificity of bovine colostrum CMP NeuAc:Gal beta 1----4GlcNAc-R alpha 2----6-sialyltransferase (alpha 6 sialyltransferase) was investigated. Initial rates of sialic acid incorporation into the desialylated glycans of hCG alpha and hCG beta in the heterodimer were higher with the alpha-subunit. This appeared to be due to a higher V which, together with a slightly lowered affinity (higher Km), resulted in a higher kinetic efficiency of the sialyltransferase for the glycans of this subunit. By contrast, the kinetic parameters did not differ significantly when the subunits were in the free form, indicating that the differences in the kinetics of sialylation found for the subunits in the heterodimeric state were not caused by the differences in N-linked carbohydrate structures of the subunits. It is proposed that these effects are due to conformational constraints which the polypeptide moieties put on the glycan chains upon dimerization. Furthermore, it was investigated whether the polypeptide of hCG would interfere with the sialyltransferase so as to alter the branch specificity of the enzyme. 1H-NMR spectroscopy (400 MHz) of the glycan chains, alpha 6-sialylated in vitro, showed that the enzyme highly prefers the galactosyl residue at the Gal beta 1--- 4GlcNAc beta 1----2-Man alpha 1----3Man branch for attachment of the first mol of sialic acid into the diantennary glycans of desialylated hCG.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606354 TI - Epidemiology of hypertension in the elderly. AB - Epidemiological studies confirm that hypertension, particularly systolic hypertension, is a major cardiovascular and cerebrovascular risk factor in the elderly. Clinical trials convincingly demonstrate the benefits of treating both diastolic hypertension in persons up to age 80 years, and isolated systolic hypertension in persons over age 60. The European Working Party on Hypertension in the Elderly (EWPHE) trial showed that reducing elevated blood pressure resulted in a 27% reduction in overall cardiovascular mortality, as well as significant reductions in severe congestive heart failure, strokes and deaths from myocardial infarction. The Systolic Hypertension in the Elderly Program (SHEP) also reported a 36% reduction in the incidence of stroke and decreases in cardiovascular events, including myocardial infarctions, when hypertension was treated. Additional EWPHE data suggest that the optimal level of systolic blood pressure control is between 146 and 158mm Hg, while patients in the SHEP trial with isolated systolic hypertension derived benefits at an average treated systolic blood pressure of 143mm Hg. Elderly study populations comply well with antihypertensive treatment, and blood pressure can be safely lowered with simple drug regimens. Nonpharmacological treatment is recommended for initial treatment of mild diastolic hypertension and isolated systolic hypertension, and as adjuvant treatment with medication. Since all antihypertensive agents can lower blood pressure in the elderly, therapy should be chosen based on its potential for side effects, drug interactions and effects on concomitant disease states. PMID- 1606357 TI - Different fates of the oligosaccharide moieties of lipid intermediates. AB - We have previously described that the N-glycosylation process was accompanied by the release of oligosaccharide-phosphates and neutral oligosaccharides. The relationship between oligosaccharide-P-P-dolichol and its metabolic products (glycoproteins, oligosaccharide-phosphates and neutral oligosaccharides) was investigated by analysing the structure of the oligosaccharide moieties and the kinetic behaviour of the various species in pulse and pulse/chase experiments. For these studies, a glycosylation mutant of Chinese hamster ovary cells (B3F7) which does not synthesize mannosylphosphoryldolichol was utilized. Evidence was obtained for the presence of two pools of oligosaccharide-P-P-dolichol which have different fates. One pool is not glucosylated, is rapidly labelled and immediately chased by mannose, and generates the oligosaccharide-phosphate species. The second pool is glucosylated, exhibits a lag time (5-10 min) prior to being labelled, and is utilized in the glycosylation of proteins and in the production of neutral oligosaccharides. We postulate that the cleavage of non glycosylated lipid intermediates generating oligosaccharide-phosphates represents a 'bypass' in the dolichol cycle which allows direct regeneration of dolichyl phosphate. The other metabolic fate of non-glucosylated oligosaccharide-lipids, glucosylation, results in their use as effective substrates for the glycosylation of proteins or in the generation of neutral oligosaccharides. PMID- 1606355 TI - Age-related changes in hepatic function. Implications for drug therapy. AB - An age-related decrease in the hepatic clearance of many drugs has been reported. Several mechanisms have been proposed, but only some are supported by hard evidence. Liver volume declines with age, as does hepatic blood flow--changes which may largely account for the reduced clearance of capacity- and flow-limited drugs, respectively. Age-related histological changes in the liver are minor and of uncertain significance; standard liver function tests do not change significantly with aging. There is, as yet, no direct evidence of a generalised fall in hepatic drug-metabolising enzyme activities in aging humans measured in vitro, but some in vivo studies suggest that certain very specific cytochrome P450 isoenzymes may be affected by aging, especially in men. Finally, there may be an age-related decline in the response to environmental influences. PMID- 1606358 TI - The c-series gangliosides GT3, GT2 and GP1c are formed in rat liver Golgi by the same set of glycosyltransferases that catalyse the biosynthesis of asialo-, a- and b-series gangliosides. AB - Biosynthesis of the c-series gangliosides GT3, GT2 and GP1c was studied in Golgi derived from rat liver. Competition experiments show that the synthesis of ganglioside GT2 (GalNAc beta 1----4-(NeuAc alpha 2----8NeuAc alpha 2----8NeuAc alpha 2----3)Gal- beta 1----4Glc beta 1----1Cer) from GT3 (NeuAc alpha 2--- 8NeuAc alpha 2----8-NeuAc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) seems to be catalysed by the same N-acetylgalactosaminyl-transferase (GalNAc-T), which converts GM3 (NeuAc alpha 2----3Gal beta 1----4Glc beta 1----1Cer) to GM2 (GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1Cer). Similar competition experiments suggest moreover that the sialytransferase V (SAT V), which catalyses the synthesis of GT1a (NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----3GalNAc beta 1----4- (NeuAc alpha 2----3)-Gal beta 1----4Glc beta 1--- 1Cer) from GD1a (NeuAc alpha-2----3Gal beta 1----3GalNAc beta 1----4(NeuAc alpha 2----3)Gal beta 1----4Glc beta 1----1-Cer) appears to be identical to the enzyme that catalyses the synthesis of GP1c (NeuAc alpha 2----8NeuAc alpha 2----3Gal beta 1----3-GalNAc beta 1----4(NeuAc alpha 2----8-NeuAc alpha 2----8NeuAc alpha 2 ---3)Gal beta-1----4Glc beta 1----4Glc beta 1----1Cer) from GQ1c (NeuAc alpha 2-- -3Gal beta 1----3Gal-NAc beta 1----4 (NeuAc alpha 2----8NeuAc alpha 2----8NeuAc alpha 2----3)Gal beta 1----4-Glc beta 1----1Cer).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606359 TI - Synthesis of four novel trisaccharides by induction of loose acceptor specificity in Gal beta 1----4 transferase (EC 2.4.1.22): Galp(beta 1----4)Glcp(X)Glc where X = beta 1----3: beta 1----4: beta 1----6: alpha 1----4. AB - Development of tandem mass spectral methods for direct linkage determination in oligosaccharides requires sets of trisaccharides differing only in one structural parameter. In this case, we chose the position of linkage to the reducing-end hexose. These sets of compounds would also be useful for the development of high resolution separation techniques geared to resolve linkage types. Conventional organic synthesis of such a set could take as long as 2-5 months for each member of the set. Each trisaccharide would require 10-20 steps of synthesis. Instead, we utilized low pH to induce a loose acceptor specificity for bovine milk galactosyltransferase (lactose synthase: EC 2.4.1.22) and by this method, within 2 weeks, generated four novel oligosaccharides for NMR and mass spectral studies. The disaccharides cellobiose (beta 1----4), laminaribiose (beta 1----3), gentiobiose (beta 1----6) and maltose (alpha 1----4) acted as acceptors for EC 2.4.1.22 under these conditions. The beta 1----2-linked disaccharide, sophorose, was not commercially available and is not included in this study. The alpha linked disaccharides were also examined, but except for the alpha 1----4 disaccharide maltose, were very poor acceptors under a variety of conditions. From these four acceptors, the following four novel trisaccharides were synthesized in micromole amounts, suitable for studies of linkage position using low-energy collision-induced-dissociation tandem mass spectrometry (FAB-MS-CID MS), and for NMR: Galp(beta 1----4)Glcp(beta 1----3)-Glc, Galp(beta 1--- 4)Glcp(beta 1----4)Glc, Galp(beta 1----4)Glcp(beta 1----6)-Glc and Galp(beta 1--- 4)Glcp(alpha 1----4)Glc. PMID- 1606360 TI - The protein and proteoglycan guises of Hermes/CD44. PMID- 1606361 TI - Glycosylation engineering. PMID- 1606362 TI - Improved surgical approach to left atrial appendage aneurysm. AB - Left atrial appendage aneurysm is a rare anomaly, which usually presents with arrhythmia or cerebral embolism. Diagnostic evaluation traditionally required cardiac catheterization, and surgical resection required cardiopulmonary bypass. Utilizing intraoperative transesophageal echocardiography and surgical stapling devices, we have streamlined our operative technique, allowing resection of a left atrial appendage aneurysm without cardiopulmonary bypass. This report of two cases treated over the past decade demonstrates the evolution of our surgical technique. PMID- 1606363 TI - Pulmonary autograft replacement of the aortic valve: an evolution of technique. AB - The use of the patient's pulmonary valve for replacement of the patient's diseased aortic valve was introduced and developed by Mr. Donald Ross. Its demonstrated durability, freedom from thromboembolism, and potential for growth has led to increased utilization of this technique. Modifications of the earlier techniques have led to a reproducible operation with low operative risk and excellent mid-term results. PMID- 1606364 TI - The replacement of the ascending aorta and aortic valve with a new design composite graft: a six-year experience. AB - The problems encountered in coronary artery reattachment when the ascending aorta and aortic valve are replaced with a composite graft induced Gallucci and one of the authors to develop a new aortovalvular prosthesis in clinical practice. The unique transverse ovoidal shape of this graft is intended to conform to the natural aortic root and facilitate the coronary anastomoses and minimize bleeding. We present our 6-year experience with 56 patients operated upon with this prosthesis. In all patients we were able to connect the coronary arteries directly to the graft without complications including hemorrhage or distortion of the coronary ostia. The survivors were evaluated with chest X ray, two dimensional echocardiography, and conventional or digital subtraction angiography to detect the presence of pseudoaneurysms at the site of the coronary anastomosis, reported by others that have used the composite graft technique. The notable absence of this complication in our patients at a mean follow-up of 41 months (range 3-71) documents that this ovoidal composite graft is a reliable tool in the treatment of aortic root pathology. PMID- 1606365 TI - One and one-half year experience with unilateral and bilateral lung transplantation. AB - Lung transplantation has now become an established form of treatment for end stage pulmonary parenchymal and vascular diseases. Despite its wide acceptance, technical aspects are still in discussion. We report on the initiation of our own lung transplant program and the technical changes we have performed during our first 1 1/2-year experience. During that period of time, we have performed 26 lung transplantations (16 single lung [SLTX] and 10 bilateral lung transplantations [BLTX]). Three-month survival for the whole group was 74% (69% for the SLTX group and 77% for the BLTX group). No instance of bronchial dehiscence was observed; however, there were eight cases of bronchial stenosis: six were managed by silicone stent insertion, one by bronchoplastic correction, and one by retransplantation. Changes in the technique of the bronchial anastomosis together with the addition of prednisone to the immediate postoperative immunosuppressive regime resulted in almost complete avoidance of these problems. PMID- 1606366 TI - Cerebral consequences of hypothermic circulatory arrest in adults. AB - Despite widespread use of hypothermic circulatory arrest (HCA) in aneurysm surgery and for repair of congenital heart defects, there is continued concern about possible adverse cerebral sequelae. The search for ways to improve implementation of HCA has inspired retrospective clinical studies to try to identify risk factors for cerebral injury, and clinical and laboratory investigations to explore the physiology of HCA. At present, risk factors associated with less favorable cerebral outcome after HCA include: prolonged duration of HCA (usually greater than 60 min); advanced patient age; rapid cooling (less than 20 min); hyperglycemia either before HCA or during reperfusion; preoperative cyanosis or lack of adequate hemodilution; evidence of increased oxygen extraction before HCA or during reperfusion; and delayed reappearance of electroencephalogram (EEG) or marked EEG abnormality. Strategies advocated to increase safety of HCA include: pretreatment with barbiturates and steroids; use of alpha-stat pH regulation during cooling and rewarming; intraoperative monitoring of EEG; slow and adequate cooling, including packing of the head in ice; monitoring of jugular venous oxygen content; hemodilution; and avoidance of hyperglycemia. Current investigation focuses on delineating the relationship of cerebral blood flow (CBF) to cerebral oxygen consumption and glucose metabolism during cooling, HCA, rewarming, and later recovery, and identifying changes in acute intraoperative parameters, including the presence of intracerebral enzymes in cerebral spinal fluid, with cerebral outcome as assessed by neurological evaluation, quantitative EEG, and postmortem histology. Clinically, intraoperative monitoring of EEG and measurement of CBF by tracer washout or Doppler flows are contributing to better understanding of the physiology of HCA, and in the laboratory, nuclear magnetic resonance (NMR) spectroscopy has provided valuable insights into the kinetics of intracerebral energy metabolism. Promising strategies for the future include investigation of other pharmacological agents to increase cerebral protection, and use of "cerebroplegia" or intermittent perfusion between intervals of HCA to improve cerebral tolerance for longer durations of HCA. PMID- 1606368 TI - Experimental evaluation of the dialdehyde starch preserved bovine internal mammary artery as a small diameter arterial substitute. AB - A canine femoral artery model was used for evaluation of a dialdehyde starch preserved bovine internal mammary artery (BIMA) (3 and 4 mm internal diameter) in comparison to a polytetrafluoroethylene (PTFE) graft. The study comprised three groups for a 2-hour (n = 7, 3 mm), 3-month (n = 10, 4 mm), and 6-month (n = 10, 4 mm) follow-up. The thrombogenicity of the grafts was measured after 2 hours and 3 months using chromium 51 labeled autologous platelets. In addition, compliance studies were done. To control the wall stability of the xenografts, the collagen content before implantation and after explantation was examined together with the diameter of the grafts. Healing characteristics were studied using appropriate histologic methods. The acute platelet adhesion rate (2 hours) of the BIMA graft was 181 +/- 69 x 10(4) platelets/mm2 as compared to 57 +/- 43 x 10(4) for PTFE (p less than 0.05, t-test). However, after 3 months the thrombogenicity of the biograft had decreased whereas the platelet count at the PTFE graft had increased (BIMA: 79 +/- 48 x 10(4); PTFE: 179 +/- 102 x 10(4), p less than 0.05). At implantation, the compliance of the BIMA graft was 0.028% +/- 0.009% per mmHg as compared to 0.06% +/- 0.0025% of the femoral artery. The PTFE graft was uncompliant (0.008 +/- 0.005). After 6 months, the compliance of the femoral artery had decreased to 0.039% +/- 0.013% per mmHg, which was now well matched to the nearly unchanged compliance of the biograft (0.0027 +/- 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606367 TI - Glutaraldehyde-fixed bovine iliac veins used as bioprosthetic conduits: an experimental animal study. AB - The ideal prosthetic conduit for surgical repair of complex congenital heart disease has yet to be found. Twenty conduits were implanted between the right ventricle and pulmonary artery in growing sheep as follows: four Dacron porcine valve conduits (mean time in place, 142 days); four avalved glutaraldehyde-fixed bovine iliac veins (mean 132 days); and 12 glutaraldehyde-fixed bovine iliac veins containing a porcine valve (mean 180 days). Fifteen conduits were left in place from 167 to 244 days (mean 204 days), and five were explanted earlier (mean 54 days). Pathological study included gross, x-ray, histological, and ultrastructural investigation. Five conduits failed because of infective endocarditis. The valved Dacron conduits showed significant tissue ingrowth and calcification of the valve graft. The valved bovine iliac veins presented calcification at the valve level and vein wall, as well as a valvelike calcific fibrous ridge at the proximal anastomosis with the right ventricle. The avalved bovine iliac veins also presented calcific deposits along the wall and a valvelike calcific ridge at the ventricular anastomosis. Histological and ultrastructural studies of the vein tunica media revealed the phenomena of inflammatory rejection and foreign body reaction with loss of smooth muscle cells (medionecrosis) and fibrotic replacement. In conclusion, bovine iliac veins undergo inflammation with medionecrosis indicating that smooth muscle cell antigenicity is not attenuated by glutaraldehyde fixation. PMID- 1606369 TI - Cryopreserved vein transplantation. AB - There have been numerous attempts to develop prosthetic conduits or utilize allograft saphenous veins for arterial bypass. This article summarizes our experimental and clinical experience with cryopreserved allograft saphenous veins. During these studies, particular attention was paid to vein donor postmortem ischemia time, vein procurement technique, and tissue storage methods. Experimental cryopreserved autograft studies demonstrated that cryopreservation of the veins does not alter subsequent graft patency, the arterialization process, blood flow, or platelet deposition in vein grafts. Endothelium-derived relaxing and contractile factors are produced by the endothelium of explanted cryopreserved autografts, and smooth muscle contractions and relaxations can be induced. In experimental cryopreserved allografts, the endothelium appears to be removed by an immune response during the first 10 days after transplantation, fibrin deposition is minimal, and re-endothelialization occurs over 6-9 months. Early clinical results using cryopreserved allograft saphenous veins are encouraging with 1-year patency rates of 79% for peripheral grafts and 86% for coronary bypass grafts. PMID- 1606370 TI - Molecular approaches to the characterization of cell and blood/biomaterial interactions. AB - In order to address questions related to cell/biomaterial interactions with respect to cell function and production of extracellular matrix proteins that support or maintain cell/tissue specific properties, we have developed molecular approaches for analysis of in vivo implanted materials and in vitro studies. In an explant of a human left ventricular assist device (LVAD), intact total cellular RNA could be isolated in sufficient quantities for hybridization analyses with gene-specific probes to evaluate cell growth, cytoskeletal organization, and production of extracellular matrix proteins. Cells harvested from a 132-day implanted LVAD exhibited proliferative activity and expressed genes for fibronectin and collagen types I, III, and IV. In vitro studies revealed that endothelial cells cultured on two different segmented polyurethane biomaterials (Biomer and Tecoflex 60D) exhibited different patterns of gene expression that reflected differences in cell growth rates, morphology, and composition of the extracellular matrix. These methodologies provide a valuable approach for a detailed evaluation of: (1) the biocompatibility of cells colonizing implanted cardiac assist devices; and (2) the functionality of cells seeded onto biomaterials. PMID- 1606371 TI - Erroneous sizing of valve bioprostheses? PMID- 1606372 TI - Cryopreserved pulmonary homograft. PMID- 1606373 TI - The use of the transpillar posterolateral approach to resect cervical osteoid osteomas: operative technique and results. AB - Osteoid osteomas located in the cervical spine are a rare cause of cervical and shoulder pain. However, successful diagnosis of these tumors has become more frequent in the recent years. This is due to more available diagnostic modalities as well as to physician awareness of the possibility that such lesions can cause cervical pain syndrome. Resection of osteoid osteomas located close to the vertebral artery is often technically difficult, and poses significant risk to the patient. We describe resection of such tumors using a posterolateral transpillar approach in three patients. The advantage of this approach is the direct and relatively easy visualization of the tumor, without the need for an extensive dissection. The stability of the cervical spine is not compromised by this approach. However, extension of the operative field is difficult, should the need arise. PMID- 1606374 TI - Placement of anterior cervical instrumentation without intraoperative radiography. AB - Adequate fixation with several commonly used anterior cervical plate systems requires that the screws penetrate both the anterior and posterior cortices of the vertebral bodies. This report emphasizes the shortcomings of plain film and fluoroscopic examinations in confirming screw position through the posterior vertebral cortex in three patients with lower cervical trauma or tumor. These cases and radiographs of isolated vertebrae from the cervicothoracic region demonstrate the inadequacy of plain film/fluoroscopy for determination of the position of anterior cervical plate screws in relation to the posterior cortex. Only axial images such as those obtained with computed tomography are able to show the exact relationship of the screws to the posterior cortical curvature in C7 and T1. PMID- 1606375 TI - Age-related disk degeneration: preliminary report of a naturally occurring baboon model. AB - Anteroposterior and lateral radiographs of 126 adult baboons were reviewed. The mean age was 15.7 years (range 6-30 years). Evidence of disk degeneration, to include disk-space narrowing, osteophyte formation, endplate changes, and facet joint arthropathy, was noted, and a grading scale, grades 0-3, was used to assign each animal an overall grade for degree of disk degeneration. Lateral radiographs were measured in the area of maximal sagittal plane curvatures. Radiographic review demonstrated a strongly positive correlation between the age of the baboons and the degree of degenerative change (p less than 0.0001), between the degree of kyphosis and the degree of degenerative change (p less than 0.0001), and between the age of the animal and the degree of kyphosis (p less than 0.001). This pilot study demonstrates plain radiographic confirmation of a naturally occurring primate model of disk degeneration, the first such model described, and is the basis for further investigation into magnetic resonance imaging and histopathologic confirmation of this model. PMID- 1606376 TI - Transpedicular short-segment fusions for treatment of lumbar burst fractures. AB - A retrospective review of 13 patients who underwent decompression and transpedicular instrumentation for lumbar burst fractures is presented. Average follow-up was 22.5 months. Eighty-four percent of patients reported little or no pain at follow-up. Sixty-nine percent of patients returned to full preinjury activity. Radiographic review demonstrated an average postoperative progression of kyphosis of 8.7%. Anterior vertebral body height was unchanged between preoperative evaluation and follow-up. Although short-segment posterior transpedicular instrumentation with VSP plates did not reestablish or maintain anatomic alignment of the lumbar spine after burst fractures, the clinical outcome was excellent. PMID- 1606377 TI - Does the Millon Behavioral Health Inventory (MBHI) predict lumbar laminectomy outcome? A comparison with the Minnesota Multiphasic Personality Inventory (MMPI). AB - Response to surgery for low-back pain is influenced by psychosocial as well as physical factors. However, no psychosocial measure has yet been found to be highly accurate in predicting surgical outcome for individual patients. The purpose of this prospective study was to assess the usefulness of the Millon Behavioral Health Inventory (MBHI) in predicting outcome of laminectomy for lumbar disc herniation or spinal stenosis. Its use was compared with that of the Minnesota Multiphasic Personality Inventory. The influence of several demographic, clinical, and radiographic variables was also investigated. One hundred twenty-seven patients were assessed at an average of 24 months postsurgery. Ninety-three patients had a good outcome, 20 had a fair outcome, and 14 had a poor outcome. The MBHI scales as a group were not associated with surgical outcome. PMID- 1606378 TI - Micturitional disturbance in tumors of the lumbosacral area. AB - Neurourological studies were performed on 15 patients with tumors at or below the first lumbar vertebra. Micturitional history revealed that 14 patients (93%) had voiding symptoms. Four patients had incontinence and three had urinary retention. Urodynamic studies revealed that three of six patients tested had abnormal uroflowmetrograms. Urinary residuals greater than 100 ml were observed in 6 of 12 patients. Detrusor hyperreflexia occurred in 3 of 15 patients, 4 of 15 had low compliance detrusor, and 2 of 15 had detrusor-sphincter dyssynergia. There were no differences in lower-extremity neurological signs in patients with or without incontinence, and patients with or without large residual urine and urinary retention. PMID- 1606379 TI - Measurement of height loss during whole body vibrations. AB - An experimental, in vivo study was performed to measure height changes in subjects exposed to whole body vibrations while seated. Twelve women, with an average age of 22 years, were exposed to sinusoidal vibrations for 5 mins. The vibration frequency was 5 Hz, and the acceleration was 0.1 g Rms. The height loss stemming from vibration exposure was compared with that experienced while sitting without being subjected to vibrations. The height losses that always occurred from the two exposures were corrected for the effect of posture change. The height loss from vibration was significantly greater than when no vibration was present. Height loss due to posture change was responsible for approximately 50% of the total height loss. From this study it was concluded that whole body vibrations cause increased height loss. PMID- 1606380 TI - Osteoid osteoma and osteoblastoma of the spine. AB - Eleven patients with spinal osteoid osteoma and six patients with spinal osteoblastoma treated between 1975 and 1990 were reviewed to characterize the tumors as they affect the spine and to define the important differences between the two tumors. All patients with cervical osteoid osteoma presented with pain, limited range of motion of the neck, and torticollis. Four osteoblastomas had soft-tissue components in the epidural space, necessitating dissection of the tumor from the dura. No soft-tissue component was found in any of the osteoid osteomas. Our results were similar to a metaanalysis of the clinical, radiographic, and surgical findings of all published cases of spinal osteoid osteoma and osteoblastoma. Important features that have not been emphasized in the literature are the high incidence of torticollis with cervical lesions and the frequent association of epidural invasion with osteoblastoma. Surgeons treating osteoblastoma of the spine should be prepared to dissect tumor from the dura. PMID- 1606381 TI - Spinal cord infarction: MRI and MEP findings in three cases. AB - We report findings of magnetic resonance imaging (MRI) in three patients with spinal cord ischemia. While myelography was normal in all three patients, MRI found pathological signal increase on the T2-weighted images in each case. Signal changes in T1-weighted images of hemorrhagic infarction were seen in one patient, and gadolinium-DTPA enhancement because of a disturbed blood-tissue barrier was noted in another. Motor evoked potentials after transcortical magnetic stimulation showed normal latencies with very low amplitudes as a sign of axonal loss in ischemia of the spinal cord. PMID- 1606382 TI - Postlaminectomy aortic pseudoaneurysm. AB - Vascular injuries after lumbar laminectomy for disc disease may result in acute life-threatening hemorrhage, chronic arteriovenous fistula, or pseudoaneurysm formation. This case report concerns a 53-year-old woman who developed an aortic pseudoaneurysm after an L2/L3 lumbar discectomy, diagnosed by abdominal computed tomography (CT) scan and aortogram. The patient fully recovered after celiotomy and repair of the aortic tear. The majority of vascular injuries associated with lumbar laminectomy are found at the L4/L5 and L5/S1 levels, and few occur at L2/L3. Early diagnosis with CT scan and aortography is essential, because prompt exploration will minimize morbidity and mortality. PMID- 1606383 TI - Fracture of the S1 vertebral body in a patient with ankylosing spondylitis. AB - We report an unusual case of spinal fracture in ankylosing spondylitis. The fracture occurred through the S1 vertebral body and resembled a traumatic spondylolisthesis. Treatment consisted of prompt operative intervention after extensive diagnostic evaluation. The case emphasizes the difficulty of diagnosing spinal fractures in those with ankylosing spondylitis, the necessity for being alert to the possibility of fracture in this group, and the value of early surgical intervention for sacral fractures with neural deficit. PMID- 1606384 TI - Syringomyelia and Chiari I malformation presenting with juvenile scoliosis as sole manifestation. PMID- 1606385 TI - Epidermal growth factor in human and bovine milk. AB - The concentration of epidermal growth factor in human and bovine milk was measured by radioreceptor assay. Both human placental plasma membranes and a human epidermoid carcinoma cell were used as the epidermal growth factor receptor source in the assay. The use of placental plasma membrane in the radioreceptor assay gave erroneous results for bovine milk and overestimated the concentration of epidermal growth factor in human milk. Intact cells appear to provide a more accurate measure of the concentration of epidermal growth factor in milk samples. Using A431 cells, we found very low concentrations of epidermal growth factor in bovine milk (less than 2 ng/ml) compared to human milk (30-40 ng/ml). No epidermal growth factor activity was found in several cows' milk-based infant formulas. These results highlight the caution which must be taken when measuring trace substances such as polypeptide growth factors in complex samples such as milk. PMID- 1606386 TI - Selenium and human lactation in Australia: milk and blood selenium levels in lactating women, and selenium intakes of their breast-fed infants. AB - A series of 20 mother-infant pairs were studied in Brisbane, Australia, at 6-12 weeks postpartum. The mean selenium concentration in maternal blood was 101 (SD +/- 19) ng/g and in maternal serum 81(+/- 15) ng/g; serum values appeared low in comparison with those reported for lactating women from Japan and the USA, but similar to those from Finland and from a previous Australian study. Breast milk selenium concentrations (11.9 +/- 3.5 ng/g) were also low by international standards, but not as low as in New Zealand or Scandinavia. There was no correlation between selenium concentrations in milk and blood (or serum). The infants' 24-h breast-milk intakes were 856 +/- 172 g, and their 24-h selenium intakes 10.7 +/- 4.1 micrograms (compared to the Australian RDI of 10 micrograms). PMID- 1606387 TI - A comparison of secretory antibodies in breast-fed and formula-fed infants over the first six months of life. AB - In the present study salivary IgA, anti-Escherichia coli, anti-beta-lactoglobulin and anti-poliovirus type 1 IgA and IgM in serum and saliva were evaluated longitudinally in 13 breast-fed and 14 formula-fed infants over the first six months of life. Salivary IgA was quantified by electroimmunodiffusion; specific IgA and IgM antibodies were determined in serum and saliva by ELISA. Salivary IgA was significantly lower at age one month in breast-fed compared with formula-fed infants but in breast-fed infants salivary IgA increased with age and was significantly higher at six months than at one month. In both groups of infants, at the age of six months, salivary IgA levels were significantly lower than in adult controls. No significant differences in secretory anti-E. coli were observed between the two groups of infants. Salivary anti-poliovirus IgA and IgM antibodies increased transiently only to disappear in most babies at age six months, while anti-beta lactoglobulin IgA and IgM, present in saliva at all ages, showed a wide scatter. No important differences in specific serum IgA or IgM antibodies were observed either between the groups or at different times within the groups. PMID- 1606388 TI - Trans fatty acids may impair biosynthesis of long-chain polyunsaturates and growth in man. AB - Human diet contains large amounts of trans fatty acids originating primarily from hydrogenated fats. Consumption of trans fatty acids is considered safe for man, but side effects, including impaired biosynthesis of long-chain polyunsaturated fatty acids with 20 and 22 carbon atoms and reduced growth have been observed in animals. We studied whether or not there are indications of untoward effects of trans fatty acids in 29 premature infants (birth weight 1700 +/- 127 g, gestational age 33.6 +/- 1.4 weeks, mean +/- SD). Plasma samples obtained on day 4 of life were analysed for fatty acid composition. Trans octadecenoic acid and total trans fatty acids in plasma lipid fractions (% wt/wt) were not related to the precursor essential fatty acids linoleic and alpha-linolenic acids but correlated inversely to n - 3 and n - 6 long-chain polyunsaturated fatty acids and to the product/substrate ratios of long-chain polyunsaturate biosynthesis. Trans fatty acids were also inversely correlated to birth weight but not to gestational age. These data indicate a potential impairment of essential fatty acid metabolism and early growth by trans isomers in man, and question the safety of high dietary trans isomer intakes during pregnancy and the perinatal period. PMID- 1606389 TI - Hyperinflation in premature infants at preschool age. AB - Functional residual capacity was measured by helium gas dilution in 12 children born very preterm (gestational age 25-29 weeks). The children were studied at between 4.0 and 4.6 years of age. Their results were compared to those of 12 control children who were born at term without neonatal problems. The controls were matched to the children born preterm for age, race and gender. The children born preterm had significantly increased functional residual capacity values when compared to the control subjects (p less than 0.01). Eight children born preterm were hyperinflated (functional residual capacity greater than 120% of that predicted for height) compared to only one control subject (p less than 0.01). Five children born preterm and one control had a positive response to bronchodilator administration. These results suggest infants born very preterm may suffer from chronic hyperinflation. PMID- 1606390 TI - The growth of low-birth-weight children. AB - The growth of 171 seven-year-old children, free from major disability, with a birth weight of 2000 g or less was examined and compared with that of their own parents and of normal-birth-weight peers. Measurements included height, weight, occipitofrontal circumference, biparietal, occipitofrontal and bi-iliac diameters, triceps and subscapular skinfold thickness. Low-birth-weight children were shorter than their parents whereas those of normal birth weight were taller. For all parameters, particularly weight, the low-birth-weight children were significantly less well grown. There was no significant relationship between occipitofrontal circumference and intellectual ability. PMID- 1606391 TI - Cholesterol screening of seven-year-old children. How to identify children at risk. AB - An inquiry was distributed to the parents of 1052 seven-year-old school beginners, concerning three issues, i.e. a known family history of myocardial infarction, angina pectoris before the age of 55 years and hyperlipidemia. A total of 147 children with a known family history were included in the study and compared with 148 classmates as control subjects. The proband children were subgrouped according to heredity factors and subjected to multivariate analysis at the 5% significance level for serum cholesterol fractions and triglycerides vs the control group. Statistically significant increased levels of total cholesterol and low density lipoprotein cholesterol, as well as an increased low density lipoprotein cholesterol and high density lipoprotein cholesterol ratio were found for all groups with hereditary for hyperlipidemia (p less than 0.001). However, no statistically significant difference was observed in the groups with heredity for myocardial infarction or angina pectoris exclusively. Also, there was no difference in any of the risk groups for high density lipoprotein cholesterol and triglycerides. The serum cholesterol levels in the present study were, to our knowledge, higher than those found elsewhere, except for Finland. PMID- 1606392 TI - Reduced haemoglobin levels in infants presenting with apparent life-threatening events--a retrospective investigation. AB - Anaemia has been shown to be associated with an increased apnoeic pause frequency and with cyanotic breath-holding spells. In this study, the relationship between anaemia and apparent life-threatening events was retrospectively investigated in 72 term infants referred for assessment and home monitoring following an apparent life-threatening event. For 41 infants (25 male, 16 female; 38 Caucasian, three Asian) a venous red blood cell count was available. Their median age at the time of the apparent life-threatening event was 2.0 (0.6-6.7) months. The Hb levels in these 41 infants were plotted against normal data from the literature. Thirty four infants had Hb levels below the mean, whilst six infants had values above the corresponding normal mean; the one remaining infant had a Hb value identical to the normal mean. Significantly more infants than expected had Hb levels below the mean (p less than 0.001, binomial test). Anaemia may have played a role in the pathophysiology leading to life-threatening events in some of the infants investigated in this study. PMID- 1606393 TI - Psychosocial growth failure: a positive response to growth hormone and placebo. AB - Seven children were diagnosed as having an emotional cause for growth failure. Pretreatment growth hormone secretion profiles during sleep were analysed using PULSAR. Mean (+/- SD) growth hormone concentration was 10.9 (4.4) mU/l, mean peak 19.6 (6.7) mU/l and the peak-to-peak interval 147 (108) min. Mean (SEM) IGF-I was 1.08 (0.31). The seven children received a six-month course of recombinant growth hormone in a double-blind, crossover study using a dose of 1.2 U/kg/week (28 U/m2/week). Daily placebo injections were given for the other six-month epoch, with a one month washout period. The mean (SEM) growth velocity SD score after growth hormone administration was +4.66 (1.88) and after placebo -0.60 (0.69), each value being greater than the pretreatment value of -2.32 (0.122) (p less than 0.0001 on analysis of variance). The change in IGF-I during growth hormone treatment was not significant. No significant changes in food energy or protein intake occurred. PMID- 1606394 TI - Ultrasonographic screening for renal abnormalities in three-year-old children. AB - We report the results of ultrasonographic screening to determine the prevalence of renal abnormalities in children. This study was conducted simultaneously with a regular health check using portable realtime ultrasound equipment, from July 1988 to June 1989. Of 2920 three-year-old children resident in Kurume City, 2351 (80.5%) were screened. Abnormalities were detected in 11 (0.47%) of these, involving six cases of pelvic dilatation, three cases of unilateral renal agenesis, and two cases of a unilaterally small kidney. However, the simultaneous urinalysis of these 11 children did not disclose these abnormalities. Our results indicate that ultrasonography is an efficient tool for screening for a silent renal abnormality. PMID- 1606395 TI - Intratracheal N-acetylcysteine use in infants with chronic lung disease. AB - To evaluate the effect of intratracheal administration of N-acetylcysteine (Mucomyst) on the clinical status, pulmonary function and gas exchange in premature infants with chronic lung disease, we conducted a randomized, placebo controlled, crossover trial. Ten mechanically ventilated infants (gestational age 27 +/- 1 week; postnatal age 22 +/- 6 days) with clinical and radiological evidence of chronic lung disease and increased airway secretion were enrolled in the study. Each infant received tracheal administration of 5% N-acetylcysteine for one week and saline placebo every 4 h for another week. N-acetylcysteine was associated with a 59 +/- 26% increase in total airway resistance by the third day of treatment (p less than 0.01). A two-fold increase in airway resistance associated with an increased frequency of bradycardia and cyanosis spells was seen in two of the infants following three days of N-acetylcysteine administration, with a rapid improvement in their condition when subsequently switched to saline. Overall, N-acetylcysteine administration had no effect on the variables measured. We conclude that intratracheal administration of N acetylcysteine to liquefy airway mucus neither improves the clinical condition nor hastens recovery in premature infants with chronic lung disease and its administration may lead to increased total airway resistance and cyanotic spells. The present data do not support the use of N-acetylcysteine as a mucolytic agent in premature infants with chronic lung disease. PMID- 1606396 TI - Home intravenous antibiotic treatment of patients with cystic fibrosis. AB - We report one-year's experience of home iv antibiotic treatment in 31 patients with cystic fibrosis chronically colonized with Pseudomonas aeruginosa. The patients were aged 4-67 years and had a mild to severe disease as indicated by a Shwachman score of 46-95 (mean 77). Ninety-two courses of iv antibiotic therapy were given (mean 3.0 per patient). The mean duration of the courses was 15.4 days. The entire antibiotic course, except for the first dose, was administered at home in 70% of the courses. Most patients (94%) were given a combined treatment of a beta-lactam and an aminoglycoside, administered by the patients themselves or their parents. One inserted venous cannula could be used for the whole treatment period in 30% of the courses. There were no complications. The clinical and bacteriological outcome was good to excellent in 89% of the courses, with temporary eradication or semi-quantitative decrease of Pseudomonas growth in sputum. Lung function (forced expiratory volume at 1 s) and blood gases improved significantly (p less than 0.001) and p less than 0.01, respectively). Most patients were able to attend work or school as usual, and 96% of the patients preferred this type of treatment to hospitalization. Apart from the psychosocial advantages, the economical savings were substantial. In comparison to traditional treatments in hospital (21 patients, 41 courses) home iv antibiotic treatment was safe and effective. PMID- 1606397 TI - Effect of phenylpropanolamine on incontinence in children with neurogenic bladders. A double-blind crossover study. AB - In children with myelodysplasia and a low-level spinal cord lesion (low lumbar sacral), detrusor hyperactivity together with dyssynergic urethral function forms the main pathophysiological basis for incontinence. Pharmacological treatment of incontinence due to neurogenic bladder dysfunction has been tried, mainly with anticholinergics and alpha-adrenoceptor antagonists. In this study, the effects of the alpha-adrenoceptor agonist phenylpropanolamine on urodynamic parameters and incontinence were investigated in 10 patients. Effects on incontinence were evaluated in a double-blind crossover trial. Plasma concentrations of phenylpropanolamine were measured by means of gas chromatography-mass spectrometry. Phenylpropanolamine reduced detrusor hyperactivity and improved continence, but the effect was not so pronounced as to make the patients continent. PMID- 1606398 TI - Prophylaxis of patent ductus arteriosus using ethamsylate in preterms treated with exogenous surfactant. PMID- 1606399 TI - Elastase alpha 1-proteinase inhibitor plasma concentration in late onset neonatal septicaemia caused by coagulase-negative staphylococci and gram-negative bacteria. PMID- 1606400 TI - Rapid onset of severe retinopathy, cataracts and neuropathy in young patients with diabetes mellitus. AB - It is rare for young diabetic patients to develop severe complications in the first years of their disease. We describe three patients, aged 14-23 years who developed cataracts and severe retinopathy within one to five years of diagnosis of diabetes. During the same period, one patient developed peripheral neuropathy and a second severe autonomic neuropathy. Rapid development of chronic complications in these patients raises the possibility that there may be a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring for complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual complaints should be evaluated carefully for evidence of treatable eye disease. PMID- 1606401 TI - Cerebrospinal fluid exchange after intrathecal methotrexate overdose. A report of two cases. AB - Two patients aged 11 and four years, were accidentally given a 10-fold overdose of intrathecal methotrexate while being treated for malignant disease. Neither patient developed any signs of neurotoxicity and exchange of lumbar cerebro spinal fluid was started 3 and 5 h later, respectively. In one of the patients, who received 120 mg of methotrexate intrathecally, 31% of the given dose was recovered during 2 h of cerebrospinal fluid exchange that was started 3 h after the accidental overdosage. No sequelae were observed in any of the patients. Cerebrospinal fluid exchange is safe and can be recommended in all cases of intrathecal methotrexate overdosage. Ventriculo-cisternal perfusion is not necessary in cases of a 10-fold overdose if the patient has no signs of acute neurotoxicity. PMID- 1606402 TI - Hyperthyroidism accelerates growth in Turner's syndrome. AB - Graves' disease in a girl with Turner's syndrome (karyotype 46,Xdel(Xp)) is described. Hyperthyroidism led to a pronounced acceleration of height velocity. During treatment with methimazole and L-thyroxine, height velocity normalized. The patient also developed spontaneous puberty with a clear-cut pubertal growth spurt. Final height, however, did not appear to be influenced either by Graves' disease or by spontaneous puberty. PMID- 1606403 TI - Vasopressin and gonadotropin deficiency in a boy with the ectrodactyly-ectodermal dysplasia-clefting syndrome. AB - A boy presented with ectrodactyly (lobster claw deformity), bilateral cleft lip and palate, semilobar holoprosencephaly and microcephaly, associated with congenital hypogonadotropic hypogonadism and central diabetes insipidus. Other aspects of pituitary function were normal. We suggest that the ectrodactyly ectodermal dysplasia-clefting syndrome can be associated with a variety of hypothalamo-pituitary dysfunctions, in addition to the already described isolated growth hormone deficiency. PMID- 1606404 TI - Intrauterine diagnosis and evolution of a cardiomyopathy in a fetus with Noonan's syndrome. AB - We report on a newborn infant with a typical form of Noonan's syndrome. Because of the presence of a fetal cystic hygroma and normal karyotype the diagnosis was suspected before birth. A progressive hypertrophic cardiomyopathy was also found following fetal echocardiographic scanning. We conclude that in addition to cystic hygroma with normal karyotype, the presence of functional or morphological evidence of myocardial abnormality should be included also as prenatal features of Noonan's syndrome. PMID- 1606405 TI - High-dose i.v. human immunoglobulin in a case with infantile opsoclonus polymyoclonia syndrome. AB - We report a 14-month-old male with infantile opsoclonus polymyoclonia syndrome. His clinical disabilities responded favorably to high-dose human immunoglobulin therapy. High dose immunoglobulin therapy is one of the therapies for patients with this syndrome. PMID- 1606406 TI - Albuminuric growth failure. A case of Munchausen syndrome by proxy. AB - A five-year-old girl presented with profound growth failure, lethargy, vomiting and acidosis. A diagnosis of Munchausen syndrome by proxy was made after the demonstration of egg albumin, diphenhydramine and phenothiazine metabolites in her urine. Growth improved dramatically, but a subsequent child in the family died of sudden infant death syndrome. PMID- 1606407 TI - Antibiotic susceptibility of 629 bacterial blood and CSF isolates from Swedish infants and the therapeutic implications. PMID- 1606408 TI - Antibiotic susceptibility of 629 bacterial blood and CSF isolates from Swedish infants and the therapeutic implications. PMID- 1606410 TI - [Early diagnosis of pancreatic cancer--is it senseless?]. PMID- 1606409 TI - Endoscopic balloon-dilatation of strictures due to inflammatory bowel disease. PMID- 1606411 TI - [Staging of pancreatic cancer: why and how?]. PMID- 1606412 TI - [Therapy of pancreatic duct calculi: cosmetic or causal therapy?]. PMID- 1606413 TI - Stenting in severe chronic pancreatitis: results of medium-term follow-up in seventy-six patients. AB - Between January 1985 and September 1989, 75 patients presenting with severe chronic pancreatitis with distal stricture and upstream dilatation underwent stenting of the main pancreatic duct (MPD) through the major papilla (n = 54) or minor papilla (n = 21) in order to drain the predominant duct through a 10F plastic prosthesis. All patients had undergone biliary and pancreatic sphincterotomy with a few cases of complications, and the majority (84%) also ESWL in the period from October 1987 onwards without complications. Relief of pain (94%) occurred parallel to a decrease in the MPD diameter. In a mean follow up period of 37 months improvement of the nutrition status and relief of pain was seen. Clogging of these large plastic stents was treated by replacement or by another endoscopic or surgical procedure. Complications were treated endoscopically. Further measures necessary due to failure of stenting consisted of laterolateral pancreatico-jejunostomy in 15% of patients and placement of self expanding 18F metal mesh stents in 29%. There was no mortality due to surgery. It is concluded that stenting of distal strictures in the MPD can lead to rapid resolution of pancreatic pain due to ductal hypertension and is the best means for determining the cause of pain, providing an alternative to surgery. Significant improvement of a stricture by prolonged stenting is however unusual, and such patients treated endoscopically require close follow-up with stent replacement approximately once a year. PMID- 1606414 TI - [Papillotomy in acute pancreatitis--more benefits than risks?]. PMID- 1606415 TI - [Papillotomy in acute pancreatitis: more benefits than risks]. AB - The pathogenesis of acute pancreatitis is still unclear. OPIE's theory that obstruction of the Ampulla of Vater can be an important etiological factor in acute pancreatitis is still relevant for the ongoing discussion whether endoscopic papillotomy can improve acute pancreatitis. Patients with severe acute pancreatitis have to undergo an early ERCP for the detection of the biliary origin of the disease. In case of the detection of choledocholithiasis endoscopic papillotomy should be performed. The rate of complications and the duration of hospitalization can be significantly reduced in contrast to conservative treatment. Controlled clinical studies are necessary to answer the question if endoscopic papillotomy should be carried out in all patients with severe acute pancreatitis. PMID- 1606416 TI - [Video-endoscopic measurement of blood circulation]. PMID- 1606417 TI - [Endoscopic Doppler in ulcer: better assessment of bleeding risk]. PMID- 1606418 TI - Endoscopic ligation of esophageal varices. AB - Endoscopic variceal ligation was developed to provide a safe alternative to conventional injection sclerotherapy which is known to be associated with a substantial incidence of non-bleeding treatment related complications. Laboratory studies in portal hypertensive dogs have shown the technique results in obliteration of vascular structures in the submucosa by scar tissue formation. The clinical technique of endoscopic ligation is performed in the endoscopy suite or intensive care unit in a fashion similar to endoscopic sclerotherapy except an endoscopic overtube is routinely employed. Initial single arm trials of endoscopic ligation in 146 consecutive patients showed the technique to be effective for control of active bleeding and eradication of varices while being associated with a low incidence of non-bleeding complications. Endoscopic ligation has been investigated in three additional single arm trials and is currently under investigation in three prospective randomized studies comparing the technique with sclerotherapy. Data from these studies have confirmed that endoscopic ligation is at least equal to sclerotherapy for treatment of actively bleeding varices and prevention of recurrent bleeding. The new technique appears to result in a significantly lower risk of non-bleeding treatment related complications than conventional sclerotherapy. PMID- 1606419 TI - [Monitoring with endoscopy: safety check for the physician or benefit for the patient?]. PMID- 1606420 TI - The post-cholecystectomy syndrome: the role of sphincter-of-Oddi dysfunction. PMID- 1606421 TI - [Endoscopic diagnosis of duodenal diseases]. PMID- 1606422 TI - The GMC on performance. PMID- 1606423 TI - Doctors, patients, and HIV. PMID- 1606424 TI - Multiple sclerosis: diagnostic optimism. PMID- 1606425 TI - Multiple sclerosis: therapeutic pessimism. PMID- 1606426 TI - Thailand stifles AIDS campaign. PMID- 1606427 TI - Osteoarthritis of the hip: an occupational disease in farmers. AB - OBJECTIVE: To test the hypothesis that farmers are at high risk of hip osteoarthritis and to investigate possible causes for such a hazard. DESIGN: Cross sectional survey. SETTING: Five rural general practices. SUBJECTS: 167 male farmers aged 60-76 and 83 controls from mainly sedentary jobs. All those without previous hip replacement underwent radiography of the hip. MAIN OUTCOME MEASURES: Hip replacement for osteoarthritis or radiological evidence of hip osteoarthritis. RESULTS: Prevalence of hip osteoarthritis was higher in farmers than controls and especially in those who had farmed for over 10 years (odds ratio 9.3, 95% confidence interval 1.9 to 44.5). The excess could not be attributed to any one type of farming, and heavy lifting seems the likely explanation. CONCLUSIONS: Manual handling in agriculture should be limited where possible. Consideration should be given to making hip osteoarthritis a prescribed industrial disease in farmers. There may be wider implications for the prevention of hip osteoarthritis in the general population. PMID- 1606428 TI - Is Helicobacter pylori the cause of dyspepsia? AB - OBJECTIVE: To determine the association between infection with Helicobacter pylori and dyspepsia. DESIGN: Cross sectional study of dyspeptic subjects and age and sex matched controls identified by a questionnaire survey of all inhabitants aged 20-69. (Endoscopy, histological examination, and microbiological examinations of biopsies from the gastric mucosa were performed blind.) SETTING: Population based survey in Sorreisa, Norway. SUBJECTS: All 782 dyspeptic subjects (excluding those with a previous history of peptic ulcer, gall stones or kidney stones, and coronary heart disease) and controls were offered an endoscopy, of whom 309 dyspeptic subjects and 310 controls attended. MAIN OUTCOME MEASURES: Prevalences of endoscopic and histological diagnoses and of cultures positive for H pylori. RESULTS: A high prevalence of positive cultures, increasing with age, was found in both dyspeptic subjects (48%) and non-dyspeptic controls (36%) (p = 0.004). Positive cultures in both dyspeptic subjects and controls were strongly associated with histological gastritis (70%, 95% confidence interval 65.5 to 85.3; 60%, 52.7 to 67.7, respectively) and peptic ulcer (92%, 61.5 to 99.8; 64.1, 9.4 to 99.2, respectively). Only 3% of subjects with a histologically non inflamed gastric mucosa had this infection (dyspeptic subjects 2%, 0.2 to 7.0; controls 4%; 1.2 to 8.8). CONCLUSIONS: The relation between dyspeptic symptoms and H pylori is dubious; H pylori seems to have a pathogenetic role in gastritis and may be a contributing factor but not a cause of peptic ulcer. PMID- 1606429 TI - Treatment of natal cleft sinus: a prospective clinical and economic evaluation. PMID- 1606430 TI - Use of Lucozade and glucagon by ambulance staff for treating hypoglycaemia. PMID- 1606431 TI - Hypercalcaemia: changing causes over the past 10 years. PMID- 1606432 TI - Investigation of QT interval in adult coeliac disease. PMID- 1606433 TI - Onchocerciasis in members of an expedition to Cameroon: role of advice before travel and long term follow up. PMID- 1606434 TI - Continuity of care in general practice: effect on patient satisfaction. AB - OBJECTIVE: To evaluate the influence of continuity of care on patient satisfaction with consultations. DESIGN: Direct and episodic specific evaluation of patient satisfaction with recent consultation. SETTING AND SUBJECTS: A representative sample of 3918 Norwegian primary care patients were asked to evaluate their consultations by filling in a questionnaire. The response rate was 78%. MAIN OUTCOME MEASURES: The patient's overall satisfaction with the consultation was rated on a six point scale. Continuity of care was recorded as the duration and intensity of the present patient-doctor relationship and as patients' perception of the present doctor being their personal doctor or not. RESULTS: The multivariate analysis indicated that an overall personal patient doctor relationship increased the odds of the patient being satisfied with the consultation sevenfold (95% confidence interval 4.9 to 9.9) as compared with consultations where no such relationships existed. The duration of the patient doctor relationship had a weak but significant association with patient satisfaction, while the intensity of contacts showed no such association. CONCLUSION: Personal, continuous care is linked with patient satisfaction. If patient satisfaction is accepted as an integral part of quality health care, reinforcing personal care may be one way of increasing this quality. PMID- 1606435 TI - Supporting elderly dependent people at home. AB - OBJECTIVE: To clarify the relation between the dependency of elderly people and the assistance they receive from others by using a detailed but simple measure of dependency. DESIGN: Secondary analysis of data from a survey of people aged 70 and over. SETTING: Two general practices in south Wales. SUBJECTS: 1280 people aged 70 and over. MAIN OUTCOME MEASURES: Dependency on others to perform essential functions; detailed data on who assists with those functions. RESULTS: Increasing dependency was associated with increased use of more than one member of the family or friends and an increase in the provision of statutory services. CONCLUSION: The complexity of the relation between dependency and those who care for dependent people has previously been underestimated. The presence of providers of statutory services at the household of elderly dependent people suggests that these services can be developed further to help those caring for elderly people at home. PMID- 1606436 TI - Psychological influences on cancer and ischaemic heart disease. PMID- 1606437 TI - ABC of colorectal diseases. Diarrhoea. PMID- 1606438 TI - Asthma deaths in New Zealand. PMID- 1606439 TI - Public health heresy. PMID- 1606440 TI - Public health heresy. PMID- 1606441 TI - Public health heresy. PMID- 1606442 TI - Routine weighing during antenatal visits. PMID- 1606443 TI - Routine weighing during antenatal visits. PMID- 1606444 TI - Perforation of gloves. PMID- 1606445 TI - Perforation of gloves. PMID- 1606446 TI - More injuries from "bouncy castles". PMID- 1606447 TI - Is the child father of the man? PMID- 1606448 TI - Patent foramen ovale and subaqua diving. PMID- 1606449 TI - Electrical stimulation of the spinal cord in peripheral vascular disease. PMID- 1606450 TI - Immunisation, not vaccination. PMID- 1606451 TI - Home based and hospital care for severe mental illness. PMID- 1606452 TI - Home based and hospital care for severe mental illness. PMID- 1606453 TI - Duplicate publication. PMID- 1606454 TI - Salami publication. PMID- 1606455 TI - Saphenous vein grafts: current problems and future prospects. PMID- 1606456 TI - Surrogacy. PMID- 1606457 TI - Antiplatelet, anticoagulant and fibrinolytic agents in acute ischaemic stroke and TIA. AB - In acute ischaemic stroke and transient ischaemic attacks both platelets and coagulation factors are activated. This is the rationale for the use of antiplatelet and anticoagulant agents in the prevention of acute ischaemic stroke. Evidence also suggests that antiplatelet agents anticoagulants and dissolution of a thrombus occluding a major cerebral vessel (by means of fibrinolytic agents) may be beneficial as therapy for the acute phase of ischaemic stroke. PMID- 1606458 TI - Pathogenesis and management of ascites in chronic liver disease. AB - The diagnosis and management of ascites related to liver diseases is discussed. We emphasize that although treating ascites improves the symptoms, it does not influence prognosis, whereas injudicious treatment may cause life-threatening side effects. PMID- 1606459 TI - Presentation and diagnosis of brain tumours. AB - The clinical presentation of brain tumours depends largely upon the biological activity, the age of the patient and the site. The presentation may be with raised intracranial pressure and/or the gradual development of focal neurological signs. The increasing availability of computed tomography and magnetic resonance imaging is changing the way patients with suspected tumours should be investigated. PMID- 1606460 TI - Current management of pleural disease. AB - The pleura may be affected by a variety of diseases. Radiological techniques are helpful in management but are rarely diagnostic. Diagnosis is usually made following careful assessment of aspirated fluid and pleural biopsy specimens. The management of pleural malignancy remains unsatisfactory. PMID- 1606461 TI - Munchausen syndrome by proxy. AB - Munchausen syndrome by proxy may result in a child suffering significant morbidity and mortality either from a parent or carer or as a result of unnecessary hospital admissions, investigations and treatment. It should therefore be considered in the differential diagnosis of any child with signs or symptoms that remain unexplained after standard investigations or are unresponsive to treatment. PMID- 1606462 TI - Hip arthroscopy. AB - Arthroscopy has become an established part of orthopaedic surgery but arthroscopy of the hip is new. It is being increasingly performed in the USA and Japan, and its use now in the UK has highlighted its advantages in the treatment of many diverse orthopaedic conditions. PMID- 1606463 TI - Surrogacy: the evolution of opinion. AB - It would seem impossible to determine an ethical framework for the practice of surrogate motherhood that does not impinge on the liberties of some or offend others. Many attempts to establish guidelines or laws result in paradox. A wide variety of interacting factors influence public opinion and intuitive assumptions may be wildly inaccurate. PMID- 1606464 TI - A look at Bottomley's vision. AB - The Conservatives have recently begun their fourth consecutive term of office. What are the implications for the NHS of a further 5 years of Tory rule and what difference, if any, will the new mistress of Richmond House make? PMID- 1606466 TI - Improved recipe for reform. PMID- 1606467 TI - Low key media response to NCEPOD. PMID- 1606465 TI - Amniotic fluid embolism: maternal mortality revisited. AB - Amiotic fluid embolism is still a significant cause of maternal mortality. It must be suspected in all cases of sudden maternal collapse. For successful resuscitation, surgical delivery should be performed without delay. PMID- 1606468 TI - No consensus yet on the benefits of digoxin. PMID- 1606469 TI - Rapid diagnosis of testicular tumour. PMID- 1606470 TI - A bizarre choice of anaesthetic technique? PMID- 1606471 TI - A bizarre choice of anaesthetic technique? PMID- 1606472 TI - Brain, skeletal muscle and platelet homogenate mitochondrial function in Parkinson's disease. AB - The recent discovery of mitochondrial complex I deficiency in the substantia nigra of patients with idiopathic Parkinson's disease has provided new understanding into the possible mechanisms that may underlie this neurodegenerative disorder. The biochemical defect is identical to that induced in humans, primates and mice exposed to the neurotoxin 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine. We have studied mitochondrial respiratory chain function in various brain regions, in skeletal muscle and in blood platelets from patients with idiopathic Parkinson's disease and from matched controls. We provide evidence suggesting that the complex I deficiency in Parkinson's disease is limited to the brain and that this defect is specific for the substantia nigra. The tissue specificity of the complex I deficiency in Parkinson's disease and its localization to the substantia nigra support the proposition that complex I deficiency may be directly involved in the cause of dopaminergic cell death in Parkinson's disease. An understanding of the molecular basis of this biochemical defect will provide valuable insight into the cause of Parkinson's disease. Our findings of normal mitochondrial function in platelet homogenates suggests that this tissue cannot be used to develop a 'diagnostic test' for Parkinson's disease. PMID- 1606473 TI - A molecular genetic study of focal histochemical defects in mitochondrial encephalomyopathies. AB - Using in situ hybridization and histochemistry we have studied muscle biopsy samples from eight patients with mitochondrial encephalomyopathies and known defects of mitochondrial DNA (mtDNA). In four patients with heteroplasmic mtDNA deletions there were focal accumulations of deleted mtDNA and its transcripts within ragged red fibres (RRF). In one of these, a probe designed specifically to detect deleted mtDNA identified abundant deleted mtDNA and its fusion transcript in RRF and lesser accumulations in non-ragged red cytochrome oxidase (COX) deficient fibres. A further patient with a deletion involving the heavy strand promoter region showed accumulation of deleted mtDNA and light strand transcripts in RRF, but concomitant depletion of all heavy strand transcripts. In all patients with deletions, normal mtDNA transcripts were depleted in COX deficient fibres irrespective of ragged red change. Deleted mtDNA was rare or absent in normal fibres. Within RRF, COX activity was more profoundly impaired in patients with deletions involving COX subunits. In two patients heteroplasmic for the base pair (bp) 3243 mutation associated with mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS), RRF contained a great excess of mtDNA and transcripts of all species. Some RRF showed excess COX activity. Non ragged red COX deficient fibres showed equal increases of ribosomal RNA (rRNA) and messenger RNA, suggesting that focal biochemical defects were not associated with a quantitative defect of transcription termination at the 3' end of the 16S rRNA which might be predicted. A patient heteroplasmic for the bp 8344 mutation (associated with myoclonic epilepsy and ragged red fibres: MERRF) showed subnormal COX activity within RRF, although the tissue distribution of mtDNA and its transcripts was similar to that seen with the bp 3243 mutation. Within mitochondrial encephalomyopathies, the relationships between the distribution and expression of abnormal mtDNA and the focal biochemical consequences are complex and heterogeneous. PMID- 1606474 TI - The left medial temporal region and schizophrenia. A PET study. AB - Regional cerebral blood flow (rCBF) was measured in 30 schizophrenic patients with severe, persistent and stable symptoms using positron emission tomography (PET). Directed and non-directed correlational analysis of the relationship between psychopathology and rCBF was used to identify brain structures implicated in three behavioural subsyndromes of schizophrenia. Psychopathology and neurophysiology (rCBF) exhibited high correlations in the left medial temporal region, mesencephalic, thalamic and left striatal structures. The highest correlation was in the left parahippocampal region. A canonical analysis of the same data highlighted the left parahippocampal region and left striatum (globus pallidus) as sites which linked the behavioural subsyndromes in terms of shared rCBF correlates. Increasing severity of psychopathology was associated with increased rCBF in these regions. Disinhibition of left medial temporal lobe activity mediated by fronto-limbic connections is a possible explanation for these findings; however, the prefrontal component appears to be critically dependent on the behavioural subsyndrome. PMID- 1606475 TI - The clinical and epidemiological profile of Lyme neuroborreliosis in Denmark 1985 1990. A prospective study of 187 patients with Borrelia burgdorferi specific intrathecal antibody production. AB - This prospective study reports the clinical and epidemiological features of 187 consecutive patients with neuroborreliosis recognized in Denmark over the 6-yr period, 1985-1990. Only patients with intrathecal Borrelia burgdorferi specific antibody synthesis were included. In 1990 regional incidences varied between 5.7 and 24.1 per million. Ninety-four percent of the patients had early (second stage) neuroborreliosis. The most common manifestation was a painful lymphocytic meningoradiculitis (Bannwarth's syndrome) either with paresis (61%) or as a radicular pain syndrome only (25%). Central nervous system (CNS) involvement in early neuroborreliosis was rare; 4% had signs of myelitis and only one patient had acute encephalitis. Children showed a different course of the disease. Six percent of the patients suffered a chronic course with a disease duration between 6 mths and 6 yrs either as chronic lymphocytic meningitis (1.6%) or as third stage chronic encephalomyelitis (4.3%). Meningeal signs were rare despite pronounced inflammatory cerebrospinal fluid (CSF) changes (median cell count 160/microliters; median protein concentration 1.13 g/l). High dose i.v. penicillin G was administered to 91% of the patients. Based on the clinical outcome and normalization of CSF no treatment failures were recognized. The final morbidity after a median follow-up of 33 mths was low; disabling sequelae were reported in nine patients, mainly those with previous CNS involvement. We conclude that neuroborreliosis is a common and characteristic neurological disorder. The diagnosis should be based on the demonstration of inflammatory CSF changes and B. burgdorferi specific intrathecal antibody production. PMID- 1606476 TI - Wavelength discrimination in blindsight. AB - In the circumscribed, long-standing, clinically absolute visual field defects of three patients with vascular lesions that involved the optic radiation and visual cortex, forced-choice discrimination between coloured stimuli was tested. Paired stimuli were matched for luminous efficiency on the basis of previous measurements of increment-threshold spectral sensitivity made in the same patients and at the same retinal positions. To different extents all patients could discriminate between narrowband wavelength stimuli. The results imply that despite the effects of retrograde degeneration on thalamic and retinal colour processing channels, neurons which process wavelength information are still functional, although the information they transmit is not consciously perceived. PMID- 1606477 TI - Eye movements in myotonic dystrophy. AB - Smooth pursuit eye movements were studied with infrared reflection equipment in 10 patients with myotonic dystrophy and in 10 age- and sex-matched controls. Smooth pursuit gain, measured after correction for catch-up saccades, was decreased in the patient group. Normal latencies of saccadic eye movements made a lack of attention an unlikely explanation for this low gain. Likewise, presence of catch-up saccades and normal fixation made it unlikely that extra-ocular myopathy explained the low smooth pursuit gain. We suggest that periventricular white matter abnormalities represent a more likely explanation. PMID- 1606478 TI - Respiratory involvement in multiple sclerosis. AB - Respiratory complications occur in advanced multiple sclerosis (MS) but may also complicate acute relapses earlier in the disease. We present 19 patients with MS who developed respiratory complications at a mean of 5.9 (range 1-12) yrs after the onset of neurological symptoms. Fourteen patients developed severe respiratory insufficiency presenting with a combination of reduced forced vital capacity (FVC), hypoxaemia or hypercapnia (12 patients) and respiratory arrest (four patients). Two patients presented with apneustic breathing, one with paroxysmal hyperventilation, one with obstructive sleep apnoea and one with bulbar weakness leading to aspiration pneumonia. Respiratory muscle weakness was a major factor in 14 patients (predominantly diaphragm involvement in six), bulbar weakness in seven patients, impaired voluntary control in three and impaired automatic control in three. Twelve patients received mechanical respiratory support of whom seven have subsequently died. The methods of support used were intermittent positive pressure ventilation (nine patients), iron lung (three), cuirass (two) and rocking bed (one). Six patients were maintained on respiratory support until they died after intervals varying from 24 h to 6 yrs (mean 17.7 mths). Five patients received temporary ventilation for between 6 d and 42 d: of these four remain alive at up to 4 yrs and one died after 16 yrs. One patient remains on domiciliary nasal intermittent positive pressure ventilation (IPPV) after 1 yr. PMID- 1606479 TI - Primary lateral sclerosis. Clinical features, neuropathology and diagnostic criteria. AB - Eight patients with a homogeneous syndrome of progressive symmetric spinobulbar spasticity were studied. Clinical features were limited to those associated with dysfunction of the descending motor tracts and included spastic quadriparesis, pseudobulbar affect, spastic dysarthria, hyper-reflexia and bilateral Babinski signs. Lower motor neuron findings were absent and higher cognitive function preserved. Median age of onset was 50.5 yrs and median disease duration was 19 yrs. Neuropathologic features (including morphometric analysis) in the single autopsied case confirmed the selective involvement of the motor cortex. There was complete absence of Betz cells from layer 5 of the precentral cortex and the remaining pyramidal cells were significantly smaller than those seen in normal controls. Magnetic resonance imaging (MRI) revealed atrophy of the precentral gyrus and positron emission tomography (PET) scans showed diminished glucose [18F]fluorodeoxyglucose uptake in the pericentral cortex. Magnetic motor cortex stimulation revealed markedly prolonged central motor conduction times. The literature is reviewed and diagnostic criteria for primary lateral sclerosis based on clinical, laboratory and imaging features are proposed. PMID- 1606480 TI - Cognitive function and regional cerebral blood flow in Parkinson's disease. AB - In order to investigate relationships between cognition and regional brain function, we studied 20 non-demented patients with idiopathic Parkinson's disease (PD), 21 mildly demented patients with Alzheimer's disease (AD) and 24 control subjects using cognitive testing and single photon emission computerized tomographic (SPECT) measurements of relative regional cerebral blood flow (rCBF). Neuropsychological tests were grouped into clusters reflecting frontal lobe executive abilities, perseveration, memory and visuospatial ability, with a summary score summarizing performance in all four of these spheres. SPECT imaging utilized the tracer [123I]N-isopropyl-p-iodoamphetamine with a relative measure of regional tracer uptake normalized to occipital radiotracer uptake (rCBF ratios). Patients with PD performed more poorly than controls in all cognitive domains, and were intermediate to AD patients and controls in tests of memory and overall cognitive functioning. Those PD patients who performed most poorly on neuropsychological testing showed lowest rCBF ratios in left and right temporal lobes. Using a stepwise multiple regression procedure, we examined patterns of correlations between cognitive clusters and predictor variables, including rCBF ratios, in the PD patients. We found that while patient age was a strong determinant of performance on the memory cluster and the summary score, dorsolateral frontal lobe perfusion and scores on a depression inventory accounted for a greater proportion of the variance of the frontal lobe and perseveration clusters than did age. These results imply that different neural mechanisms are responsible for the different aspects of cognitive decline seen in PD patients, with overall cognitive function closely related to age and temporal perfusion, while frontal lobe abilities are more linked to frontal perfusion and the presence of depression. PMID- 1606481 TI - Simple and choice reaction time and the use of advance information for motor preparation in Parkinson's disease. AB - The effects of different types of advance information (warning signal, temporal cue, movement parameter cue), presented at different intervals before an imperative stimulus on reaction time (RT) were examined. Sixteen patients with Parkinson's disease and 16 age-matched normal controls performed a simple reaction time (SRT) task, an uncued, two partially cued (cueing of direction of movement or hand) and a fully cued visual four choice reaction time (CRT) tasks. An S1-S2 paradigm was used, where a warning signal/precue (S1) preceded the imperative signal (S2) by 0 (uncued and unwarned conditions), 200 ms, 800 ms, 1600 ms or 3200 ms. When the unwarned SRT and uncued CRT conditions were compared, the patients were slower than the controls in both conditions, with the group differences being larger for the CRT than the SRT task. Both patients and controls benefited from a warning signal presented before the imperative stimulus (S2), especially when it occurred 200 ms prior to S2. Advance information about the parameters of the required response was used by both patients and controls to preprogramme responses before the onset of S2. In both groups, RTs were generally faster for longer S1-S2 intervals. With an S1-S2 interval of 3200 ms, advance information about two movement parameters was 'fully' used by the patients to preprogramme responses such that their fully cued CRT was reduced to the level of SRT. In the controls, this process was complete by 800 ms. The most parsimonious explanation of the pattern of results across the SRT, fully cued CRT and uncued CRT conditions would be in terms of a slowness in response initiation in Parkinson's disease, which is a stage of processing common to all RT conditions. Deficits at one or more of the stages of processing unique to CRT are, however, necessary to explain the differentially greater slowness of uncued CRT in Parkinson's disease. PMID- 1606483 TI - Anatomical asymmetries and functional laterality. AB - Anatomical and functional asymmetries were measured using MRI and dichotic, visual field and hand performance laterality tasks in 104 normal right- and left handed male and female adults. Comprehensive linear and area measures showed consistently larger brains when handedness and language laterality were in the same direction. Right-handers with left cerebral dominance for dichotic listening and left-handers with right cerebral dominance had larger structures. Hand performance was the strongest functional laterality related to anatomical asymmetries. Left hemisphere dominance on this task was associated with larger right frontal and left occipital widths. Dichotic listening or visual field laterality alone was not associated with contralaterally larger temporal, parietal or occipital measurements. Left visual field dominance for reading, interacting with right-handedness, was associated with wider left parietal width. The complex associations between anatomical and functional asymmetries contribute to individual differences in cerebral organization. The demonstrated association of coincident hand performance and language laterality measures with larger anatomical structures may confer biological advantage. Morphometric analysis in vivo may have increasing importance in interpreting behaviour. PMID- 1606482 TI - Human functional anatomy of visually guided finger movements. AB - The functional anatomy of visually guided movement was investigated in 18 normal subjects performing visuomotor tracking tasks during positron emission tomography imaging. Tracking a moving target with the index finger defined a network of focal responses of relative cerebral blood flow (relCBF) located in the primary motor cortex, dorsal parietal cortex, precuneate cortex, supplementary motor area (SMA) and ipsilateral anterior cerebellum relative to visual tracking alone. When the temporal complexity of the tracking task was altered by introducing a 'no go' contingency that allowed for greater time for movement preparation, there was a significant increase of relCBF in the SMA (P less than 0.0001). When the spatial complexity was augmented by adding a secondary target that provided directional cues for the primary target, there were additional significant increases of relCBF in bilateral dorsal parietal cortex (P less than 0.05) and precuneate cortex (P less than 0.05). Although the cued 'no go' task was subjectively easier, relCBF responses were similar to the uncued 'no go' task in motor areas. Performing the tracking task with different body parts produced somatotopically distributed responses in only the motor cortex. The findings are concordant with clinical reports of patients with brain lesions and physiological evidence that identifies this distributed network for performing visually guided movement. The results provide direct human evidence in the normal brain that the supplementary motor area contributes in part to the sequencing of movements and the medial and dorsal parietal cortex participates in the integration of spatial attributes during selection of movements. PMID- 1606484 TI - The plasticity of cutaneous hyperalgesia during sympathetic ganglion blockade in patients with neuropathic pain. AB - In order to investigate the plasticity of cutaneous sensory abnormalities in neuropathic pain, we monitored sensory and vasomotor effects of diagnostic sympathetic ganglion blocks in 24 patients, who suffered from chronic pain and cutaneous hyperalgesia following peripheral nerve or tissue injury. Ongoing pain was rated on a visual analogue scale, and pain evoked by innocuous tactile and cooling stimuli (hyperalgesia) on a verbal rating scale. Skin temperatures were determined at symmetric sites. In two patients, cutaneous blood flow was measured with a laser Doppler device. The sympathetic blocks led to a significant reduction of the group mean ongoing pain (40%) and cutaneous hyperalgesia (50%). Between patients, however, there was a large variability that could not be related merely to adequacy of sympathetic blockade. Neither the magnitude of change in skin temperature nor the final skin temperature after the block correlated with the amount of pain relief. The relief of hyperalgesia, however, correlated with the relief of ongoing pain. Nine patients experienced pain relief of greater than 50%. In these patients, the time course of hyperalgesia relief was similar to the time course of relief of ongoing pain. Pain relief occurred simultaneously with or a few minutes before cutaneous vasodilatation. During the block, even vigorous mechanical or cold stimuli did not rekindle hyperalgesia. In all patients, pain and hyperalgesia returned within a day after the block. In three patients tested, passive warming of the limb to the temperature achieved by the sympathetic block had negligible effects on pain and hyperalgesia. The hyperalgesia of sympathetically maintained pain is thought to be due to sensitization of central pain-signalling neurons to mechanoreceptor input. The present data indicate that this sensitization is highly plastic even when the disease has persisted for months or years. It could be reversed within minutes by a sympathetic blockade, but returned when sympathetic block subsided. Mechanoreceptor input by itself was not sufficient to maintain or rekindle the central sensitization. This supports the hypothesis that low-grade activity of nociceptors, possibly due to development of alpha-adrenergic sensitivity after injury, is involved in the maintenance of central sensitization. PMID- 1606485 TI - Early naming deficits, developmental dyslexia, and a specific deficit hypothesis. AB - The present research represents the final 2 years of a 5-year longitudinal investigation of (a) confrontation-based, word-retrieval deficits in dyslexic children; (b) the role of vocabulary development in these deficits; (c) the relationship between confrontation naming performance and three carefully defined aspects of reading performance in the general population and in eight dyslexic case studies; and (d) the possible specificity of word-retrieval deficits in dyslexia. Results indicate enduring problems in word-retrieval processes for dyslexic children across the primary grades and into middle childhood. Second, these deficits cannot be explained by simple vocabulary deficits. Third, these results in conjunction with our earlier data consolidate a pattern of differential relationships between specific reading and confrontation naming skills that are based on development and on the level of processes involved. Trends within case studies suggest the more pronounced the retrieval deficit, the more global the reading impairment. And fourth, there appear to be some specific differences in the basis of word-retrieval problems between dyslexic and garden variety or lower achieving readers. Results are discussed within a speculative framework that implicates problems in timing as a possible predetermining condition in the dyslexias. PMID- 1606486 TI - Intraindividual change in text recall of the elderly. AB - Patterns of change and variability in text recall performance were assessed in seven elderly women by testing them weekly for up to 2 years. Results showed markedly different patterns of intraindividual change in gist recall performance for different participants. The two women whose performance declined were characterized by deteriorating physical health. Texts having female protagonists yielded superior recall performance. There was significant intraindividual variability after adjustment for text effects, which may indicate that weekly fluctuations in psychological states of the participants influenced their memory performance. PMID- 1606487 TI - Brain mapping in dysphonemic dyslexia: in resting and phonemic discrimination conditions. AB - Topographic mapping of EEG bands and alpha asymmetry were analyzed during resting conditions and an auditory phonemic discrimination task (APD) in carefully screened samples of 9.0- to 12-year-old control and dysphonemic-sequencing dyslexic children. The EEG was recorded over the entire scalp, with a linked ears reference. We found: (1) no differences between groups during resting conditions in any frequency band analyzed; (2) a left hemisphere alpha responsiveness in dyslexic children during the APD condition; and (3) a beta 2 decrease in the left posterior quadrant in dyslexics during the APD condition. We conclude that the lower alpha and beta 2 responsiveness may be due to a diminished cortical reactivity and may be related to intrinsic disorganization of the neural processors associated directly with the APD task demands, the alpha activity reflecting poor attention to an external stimuli source and the beta 2 decrease reflecting an unusual processing associated with the linguistic cognitive requirements. PMID- 1606488 TI - The processing of presuppositional information contained in sentences: electrophysiological correlates. AB - In an attempt to observe how the brain processes presuppositional information, event-related potentials (ERPs) were recorded from 12 scalp electrodes placed over the left and right hemispheres of 10 adult subjects as they listened to sentences that contained either factive or nonfactive verbs. The stimulus sentences had been time-compressed to a duration of less than 1.25 sec, allowing ERPs to be recorded over their entire length. A Principal Components Analysis/Analysis of Variance procedure provided evidence that the brain responses could discriminate between factive and nonfactive conditions. It was concluded that the processing of presupposition represents a multidimensional phenomenon that changes across cortical space and time. PMID- 1606489 TI - Contextual influences in reading comprehension in aphasia. AB - Aphasic subjects' auditory comprehension of reversible passive sentences is facilitated by preceding predictive and nonpredictive narratives (Hough, Pierce, & Cannito, 1989, Brain and Language, 36, 325-334). The present study found that aphasic subjects also comprehended written reversible passive sentences significantly more accurately when they were preceded by either predictive or nonpredictive five-sentence narratives than when they were presented in isolation. Also tested was the contention that predictive narratives do not improve aphasic subjects' ability to process target sentences but simply allow these sentences to be ignored. This contention was not supported. The aphasic subjects did not comprehend predictive narratives presented without the subsequent target sentences more accurately than they comprehended the target sentences presented in isolation. For comprehension to be enhanced, both the contextual narratives and the target sentences must be present. PMID- 1606490 TI - Story processing in right-hemisphere brain-damaged patients. AB - The understanding of stories requires sensitivity to structural aspects of narrative, the emotional content conveyed by the narrative, and the interaction between structural and emotional facets of the story. Right-hemisphere-damaged (RHD) and normal control subjects performed a number of different analytic tasks which probed their competence at story comprehension. Results revealed that RHD subjects perform at a level comparable to that of normal controls with stories that follow a canonical form and that they show few difficulties with structural aspects of narrative. Contrary to expectation, they are strongly influenced by the "interest" level of a story and by other factors that tap emotional sensitivity. Findings are discussed in terms of the processing and arousal mechanisms which may give rise to the observed pattern of difficulties in RHD patients. PMID- 1606491 TI - Timing characteristics of speech after brain damage: vowel length in Thai. AB - This paper explores the extent of timing deficits in vowels produced by brain damaged speakers of a language with a phonological contrast in vowel length. Short and long vowels in Thai were produced in isolated monosyllabic words by 20 normal adults, 14 right hemisphere patients, and 17 left hemisphere aphasics. Vowel durations were measured spectrographically. Although the phonological contrast was relatively preserved, as indicated by average duration, a subtle timing deficit in vowels produced by nonfluent aphasics was indicated by a compressed duration continuum and increased variability in vowel production. PMID- 1606492 TI - Sympathetic preganglionic neurons in rabbit spinal cord that project to the stellate or the superior cervical ganglion. AB - The segmental distribution of sympathetic preganglionic neurons in the rabbit spinal cord that project to the stellate or the superior cervical ganglion was determined using retrograde tracing with cholera toxin B subunit from the stellate ganglion and wheat germ agglutinin-apo-horseradish peroxidase-gold from the superior cervical ganglion. Sympathetic preganglionic neurons that projected to the stellate ganglion were located in spinal segments T1 to T10. Sympathetic preganglionic neurons projecting to the superior cervical ganglion were found in segments T1 to T8. Both types of neuron had somata that were elongated in the rostrocaudal direction, and dendrites that were mainly confined to the intermediolateral cell column. Almost 95% of the neurons supplying the superior cervical ganglion had axons that passed through the stellate ganglion. PMID- 1606493 TI - Dependency on the brain function of arginine vasopressin system of the development to and recovery from analgesic tolerance to morphine. AB - Concomitant intracerebroventricular (i.c.v.) injection of anti-arginine vasopressin (AVP) antiserum dose-dependently suppressed the development of analgesic tolerance to daily morphine, 10 mg/kg, s.c., in mice. This suppressive effect of the antiserum was reduced by incubating the antiserum with AVP in vitro, before i.c.v. injection, suggesting that the antiserum inactivates brain AVP to result in the suppression of the development of tolerance in vivo. Similar to the antiserum, both AVP V1 and V2 antagonists given i.c.v., 10 ng and 20 ng/mouse, respectively, suppressed the development of morphine tolerance. Meanwhile, the administration of antiserum dose-dependently recovered morphine analgesia in morphine-tolerant mice and a complete recovery of analgesia was observed at the highest dose of antiserum following the second injection, and the effect of antiserum was maintained for 3 days after its withdrawal. Likewise, 10 100 ng/mouse of AVP V1 receptor antagonist given i.c.v. recovered morphine analgesia partially but significantly in a dose-dependent manner; however, AVP V2 receptor antagonist at the same doses partially recovered analgesic effect but the effect was neither significant nor dose-dependent. These findings suggest that the tolerance developed to morphine can be reversible when disturbing the function of brain AVP, but in addition to the different mechanisms of antiserum, V1 and V2 receptor antagonists, the V1 receptor-mediated mechanism may be more closely concerned in this phenomenon. PMID- 1606495 TI - Astrocytes derived from long-term primary cultures recapitulate features of astrogliosis as they re-enter the cell division cycle. AB - We investigated whether the initiation of cell cycling by astrocytes after prolonged quiescence in long-term primary cultures is associated with immunocytochemical changes that characterize reactive astrogliosis. Primary cultures of newborn rat brain were maintained for greater than 2 months in a stable quiescent state. Partially synchronous transition through a single cell cycle was achieved by trypsinization and replating, and then after 2-3 days, by 48 h of serum depletion and serum shift-up to 10% (time 0). At time 0, the percentages of cells decorated by monoclonal antibodies specific for bromodeoxyuridine (BrDU) after a 2.5 h pulse, and for glial fibrillary acidic protein (GFAP) and vimentin (VIM) were respectively 8 +/- 2, 15 +/- 4 and 10 +/- 3. By 24 h (S phase), 64 +/- 7% of nuclei were (BrDU+), and percentages of (GFAP+) and (VIM+) cells were 19 +/- 4 and 87 +/- 12, respectively. Dual label immunofluorescence showed that greater than 75% of (GFAP+) cells were indeed (VIM+/GFAP+) at 24 h, and that the percentages of (VIM+), (BrDU+) and (VIM+/BrDU+) cells were equivalent for the duration of the first cell cycle (36 48 h). By 72-96 h, (VIM+) cells decreased to less than 10%, and (BrDU+) cells numbered 32 +/- 8%, while (GFAP+) cells increased to around 90%. Ran-2 immunofluorescence at 96 h identified virtually all of the cells as type 1 astrocytes. Thus, astrocytes after months of quiescence give rise to cells that recapitulate a VIM/GFAP transition in a manner resembling astrogliosis, and do so in relation to progression through a single cell cycle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606494 TI - Repeated stressful experiences differently affect limbic dopamine release during and following stress. AB - The effects of repeated restraint stress exposures (daily 60 min, for 6 days) on extracellular dopamine in the nucleus accumbens, during and after the stress experience, have been investigated in rats by in vivo microdialysis. On the first day, restraint increased dopamine release during the first 40 min followed by a return to basal levels (50-60 min later). As soon as restraint ceased and the rats were set free, there was another increase in dopamine release lasting 40 min. On the second and third day, restraint produced only a slight increase in dopamine release, while no significant changes were evident from the fourth to the sixth day. By contrast, from the second to the sixth day the increase in dopamine release observed once rats were freed, was unchanged in comparison to the first day. The present results show that the activation of the mesolimbic dopaminergic system induced by aversive stimuli adapts to repeated experiences differently from that produced by pleasurable events, suggesting that aversive and rewarding experiences involve different neural systems. PMID- 1606496 TI - Serotonin may play a role in the anorexia induced by amphetamine injections into the lateral hypothalamus. AB - Amphetamine (AMPH) injections into the lateral hypothalamus (LH) are known to inhibit feeding and this effect has been shown to be mediated by the release and the reuptake blockade of catecholamines. LH serotonin (5-HT) has been suggested to be involved in feeding inhibition and a recent study showed that LH amphetamine infusion increases extracellular dopamine (DA), norepinephrine (NE) and 5-HT, which suggests that 5-HT might also be involved in amphetamine anorexia. The present study investigated this possibility. A correlational study was performed between the anorectic effect of LH unilateral microinjections of each monoamine and the anorectic effect of AMPH. Six groups of male rats were used. The rats in each group were submitted to 2 series of 6 experimental sessions. Each session consisted of one microinjection in 24 h food-deprived rats, followed by the measurement of food intake 30 min later. The first series was similar for all groups and explored the AMPH effect (difference between the mean food intake after 3 AMPH injections (40 micrograms/0.5 microliter) and the mean food intake after 3 saline injections (0.5 microliter)). The second series explored the effects of DA (40 micrograms), NE (25 micrograms), EPI (25 micrograms), 5-HT (25 micrograms) or AMPH again, in a similar way as described for AMPH in the first series. Linear regression analysis on the first series AMPH effect and the amine effect of the 2nd series showed a positive correlation between both series of AMPH, AMPH and DA, and AMPH and 5-HT. This last correlation was replicated in a different group. No correlation was found between AMPH and NE or AMPH and epinephrine (EPI).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606497 TI - Sensitization induced receptive field plasticity in the auditory cortex is independent of CS-modality. AB - Sensitization training with an auditory stimulus produces a general increase in response magnitude across the entire receptive field (RF) of neurons in the primary auditory cortex of the guinea pig (Bakin, J.S. and Weinberger, N.M., Brain Res., 536 (1990) 271-286). To determine if this effect reflects an auditory system-specific process or is caused by a process independent of the training stimulus modality, RFs in primary auditory cortex were characterized before and immediately after adult guinea pigs were given sensitization training with either an auditory or a visual training stimulus. General increases in auditory response magnitude across the RF were observed in 7 out of 7 auditory sensitization cases and 4 out of 5 visual sensitization cases. There were no statistical differences between the effects of auditory and visual sensitization training. These findings indicate that the general increases observed following sensitization training are the result of processes independent of CS modality, in contrast to the highly specific RF modifications that are caused by classical conditioning. The findings suggest that the 2 forms of RF plasticity, CS-specific re-tuning due to associative conditioning and polymodal general increases in gain due to non associative sensitization, may reflect neural mechanisms involved in selective attention and vigilance, respectively. PMID- 1606498 TI - Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) profiles in the amygdala of human and New World monkey (Saimiri sciureus). AB - The topographic distribution of nicotinamide adenine dinucleotide-diaphorase (NADPH-d) stained profiles in the amygdala of the human and new world monkey (Saimiri sciureus) were studied histochemically. Fiber and terminal staining were heterogeneously distributed within the amygdala. The most intense staining occurred in the basolateral subdivision, consisting of the lateral, basolateral and accessory basal nuclei. Moderate staining intensity was observed throughout the cortical and media nuclei and cortical transition area, constituents of the corticomedial subdivision. The central amygdaloid area was characterized by minimal NADPH-d histochemical reactivity. NADPH-d positive neurons were pleomorphic and divisible into two classes based on their staining characteristics: intensely or lightly stained neurons. Their distribution was generally complementary, with the majority of intensely stained neurons occupying the basolateral subdivision. There were no appreciable species differences in the patterns of neuronal, fiber and terminal staining between monkey or human amygdala. These results may be relevant to our understanding of the selective vulnerability of neural systems within the human amygdala in neurodegenerative diseases. PMID- 1606499 TI - CSF neuron-specific enolase as a quantitative marker of neuronal damage in a rat stroke model. AB - A technique for chronic cisternal cerebrospinal fluid (CSF) sampling in conscious rats was used to obtain multiple 50 microliters samples before and up to 7 days after middle cerebral artery occlusion. Neuron-specific enolase (NSE) concentrations were measured by radioimmunoassay using a readily available kit. The volume of infarction was measured by integrating the area of damage on 9 evenly spaced histological sections of the forebrain. This correlated well (r = 0.97, P less than 0.001) with the concentration of CSF neuron-specific enolase integrated over the first 5 days post occlusion, in animals with pure cortical and mixed cortical and striatal lesions. The correlation was maintained in animals given the NMDA antagonist MK-801. There was also a good correlation between the CSF NSE concentration 3 days post-MCAO and the volume of infarction (r = 0.92, P less than 0.01). It is therefore possible that CSF neuron-specific enolase may be useful as a quantitative marker of ischaemic damage in humans and provide a useful adjunct in the assessment of neuroprotective drugs in stroke. PMID- 1606500 TI - Effects of para-chloroamphetamine upon the serotonergic innervation of the rat hippocampus. AB - The ability of hippocampal serotonergic (5-HT) axons to proliferate in response to damage by para-chloroamphetamine (PCA) was examined in this study. Synaptosomal uptake of 5-HT in the hippocampal formation was decreased to 40% of control 3 days after systemic administration of PCA. Six weeks after PCA, uptake values were 44% of control. Retrograde tracing combined with 5-HT immunocytochemistry showed a significant reduction (18% of control) in the number of 5-HT raphe neurons projecting to the hippocampus 3 days after PCA. The number of 5-HT neurons projecting to the hippocampal formation increased to 69% of control by 6 weeks. The dorsal raphe nucleus was not retrogradely labeled after PCA; the increase in labeled neurons was observed in the median raphe nucleus. PHA-L, injections of the median raphe nucleus demonstrated a reduction of raphe axons in the hippocampal formation after PCA. In rats treated with PCA, raphe axons labeled with PHA-L also appeared to have fewer boutons than raphe axons labeled in control cases. The density of PHA-L containing axons in the hippocampal formation of rats injected 3 days and 6 weeks after PCA was less than control but there was no difference between the experimental groups. Based upon the results from synaptosomal uptake and anterograde tracing experiments, we feel that compensatory proliferation of 5-HT axons does not occur within 6 weeks of PCA-induced damage to the 5-HT plexus of the hippocampal formation. The data derived from the retrograde tracing experiment are thought to reflect reduced uptake and transport of WGA-HRP as an acute effect of PCA. PMID- 1606501 TI - Effects of nerve growth factor on cortical and striatal acetylcholine and dopamine release in rats with cortical devascularizing lesions. AB - The effects of intraventricular nerve growth factor (NGF) or saline treatments on extracellular acetylcholine (ACh), dopamine (DA) and adenosine (Ade) levels in the cortex and striatum of rats with unilateral devascularizing cortical lesions were studied in vivo with microdialysis. The devascularizing cortical lesion produced a decrease in extracellular ACh levels in both cortex and striatum as compared to those in normal rats, while the NGF treatment produced a significant increase in ACh levels in both regions. NGF could even increase cortical ACh levels in normal rats. The cortical lesion produced a decrease in extracellular DA in the cortex, while the NGF treatment appeared to reverse this effect. No significant changes in DA were observed in the striatum. The present study gives evidence that a unilateral cortical devascularizing lesion leads to changes in extracellular ACh and DA levels in cortex and striatum and that these changes could be reversed with intraventricular NGF treatment. PMID- 1606502 TI - Apomorphine decreases extracellular GABA in the ventral pallidum of rats with 6 OHDA lesions in the nucleus accumbens. AB - Inhibition of a tonically active gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is thought to mediate the locomotor response elicited by dopamine in the nucleus accumbens. To evaluate this hypothesis, dopamine was depleted in the nucleus accumbens using 6 hydroxydopamine which produced an upregulated locomotor response to systemic apomorphine (0.2 mg/kg, s.c.). Simultaneously, the level of extracellular GABA in the VP was monitored using microdialysis. Apomorphine injection produced an elevation in locomotor activity only in the lesioned rats. While apomorphine reduced extracellular GABA in both control and lesioned rats, the reduction had an earlier onset and was more consistent in lesioned animals. Although the onset of the decline in extracellular GABA in the VP of lesioned rats corresponded to the onset of apomorphine-induced motor activity, a significant reduction in GABA persisted for 180 min, while the behavior returned to control levels by 60 min after injection. These data support a possible role for dopamine receptor mediated inhibition of accumbal GABA neurons projecting to the VP in the initiation of locomotor activity. PMID- 1606503 TI - Differential effect of castration on the somal size of pudendal motoneurons in the adult male rat. AB - We have examined the organization of the androgen sensitivity of pudendal motoneurons in adult male rats. Comparisons of mean somal cross sectional area of pudendal motoneurons identified by retrograde labeling with horseradish peroxidase were made between three treatment groups: castrates with testosterone propionate supplementation, castrates with placebo, and sham castrates. Bulbospongiosus and ischiocavernosus motoneurons were sensitive to androgen treatment, whereas external anal sphincter and external urethral sphincter motoneurons were not. PMID- 1606504 TI - Inhibitory contacts on dendritic spines of the dentate fascia. AB - GABA-containing axon terminals were observed in the distal two-thirds of the dentate molecular layer to contact spines and dendrites of the granule cells. These contacts have the morphological characteristics of inhibitory synapses: they contain pleomorphic vesicles and have symmetrical junctional specializations. Convergence of an asymmetrical, non-GABAergic and a symmetrical, GABAergic synapse on one spine was often observed. PMID- 1606505 TI - Serotonergic influence on cholinergic-induced analgesia: differences in two inbred strains of mice. AB - C57BL/6 (C57) and DBA/2 (DBA) inbred mice showed different analgesic responses to cholinergic stimulation. The simultaneous administration of muscarinic and serotonergic agonists, oxotremorine and 5-methoxy-NN-dimethyltryptamine (5 MeODMT), lowered the antinociceptive effect of the cholinergic drug in DBA mice, while no effects were detectable in the C57 strain. These results suggest a strain-dependent behavioural effect of the interaction of cholinergic and serotonergic neuronal systems. PMID- 1606506 TI - Repeated cocaine administration induces behavioral sensitization and corresponding decreased extracellular dopamine responses in caudate and accumbens. AB - Behavioral and brain regional dopamine responses to cocaine (10 mg/kg) were concurrently monitored using in vivo microdialysis in freely-moving rats pretreated with 4 daily injections of saline or cocaine (10 mg/kg). Repeated cocaine produced a behavioral sensitization characterized by a downward oriented locomotor activation profile. In contrast, both caudate and nucleus accumbens dopamine responses were significantly diminished in the drug-pretreated group. These results, obtained following two days of drug withdrawal, differ from previous reports of an enhanced dopamine response after longer withdrawal intervals. While the duration of withdrawal may play an important role in the quantitative features of the dopamine response to subsequent stimulant administration, these results suggest that an enhanced dopamine response may not be required for the expression of behavioral sensitization. A compensatory increase in the dopamine uptake carrier, resulting from chronic cocaine-induced uptake blockade, is discussed as a possible mechanism underlying the reduced dopamine response. PMID- 1606507 TI - [Malignant mesothelioma: prognostic factors in a series of 125 patients studied from 1973 to 1987]. AB - A continuous series of 125 patients hospitalized between 1973 and 1987 with pleural malignant mesothelioma were the subjects of this stepwise analysis. A diagnostic thoracoscopy was carried out in every patient and the histopathological diagnosis confirmed by the French Mesothelioma Panel of Pathologists. The main characteristics of the patients were: mean age 64 +/- 1 year, 104 male, 21 female; previous asbestos exposure was present in 98. The histopathological type was epithelial in 90, mixed in 22, fibrosarcomatous in 13. The endoscopic aspect was analysed in the same manner from the beginning as follows: involvement of the parietal, diaphragmatic or visceral pleura; extension of the tumor into the pleural cavity, macroscopic aspects of the lesions. According to the Butchart's classification 56 patients were at stage I, 61 at stage II, 3 at stage III, 5 at stage IV. A multivariate analysis (Cox model) showed that the best prognostic factor is the stage I which can be divided in 2 subtypes: exclusive involvement of the parietal and diaphragmatic pleura without invasion of the visceral pleura: stage IA (median survival 31.2 months). It is 6.75 months as soon as the visceral pleura is invaded (stade IB). PMID- 1606508 TI - [Participation of the right hemisphere in the recovery of language in aphasics]. AB - The functional lateralization of the brain for language is a dynamic process going on during the life. The sole responsibility for ensuring normal speech lies within the neural nets of the left hemisphere. The right hemisphere who has a predominant role in extra-linguistic communication maintain a linguistic potential linked with age and modalities of lateralization. Methods allowing his activation have for first objective the recovery of an elementary communication. PMID- 1606509 TI - [Pollution in automobile interiors]. PMID- 1606510 TI - [Eulogy of Henri Jacotot 1896-1991]. PMID- 1606511 TI - [Infarcts in the region of the middle cerebral artery. Study of 501 cases in 484 patients]. AB - We report a study of 501 infarcts in the middle cerebral artery (MCA) territory, in 484 patients. All cases had an appropriate low-density area on computed tomography. The basal (perforators) territory was involved in half the cases and the motor pathways either in the pre-rolandic area or in the internal capsule in 90%. In all locations, except for watershed infarcts, the main cause was cardiac embolism. Atrial fibrillation accounted for 59%, the two other main causes were myocardial infarction and paradoxical embolism. Atherosclerosis accounted for less than one third of the cases. Among 102 internal carotid artery occlusions less than one half were due to atherosclerosis, cardiac embolism and dissecting aneurysms accounted for 22% each. None of 34 MCA occlusions were due to atherosclerotic thrombotic occlusion. Transient ischemic attacks were recorded in 22% of the cases. Stroke-in-progression with a mean duration of 6-8 hours in hospital, was noted in nearly half the cases. In a small group of MCA infarcts paralysis began and predominated on the lower limb, fifteen contralateral old MCA infarcts were silent. Ten of these were on the right side. The 15 patients with silent infarcts were all right-handed. PMID- 1606512 TI - [Role of the Acarid Euroglyphus Maynei in allergic respiratory diseases in children]. AB - The author has search specific IgE antibodies anti-Euroglyphus Maynei house dust mite among 200 children and teenagers. All had respiratory disease with a presumed allergic etiology. Specific IgE were found in eighty three subjects, all of them with hypersensitivity against Dermatophagoides pteronyssinus house dust mite. None parameter can explain this hypersensitivity but these hypersensitive subjects are older than others. PMID- 1606513 TI - A stereochemical relationship could explain the origin of the genetic code. AB - A stereochemical analysis has been carried out to investigate the possible complementarity between an RNA double helix containing thymine instead of uracil and two growing peptide chains. It is found that the optimal interactions follow the rules of the genetic code. The nature of the interaction could allow a mechanism for aminoacyl-RNA formation which could have given rise to the tRNA ancestors. Some theoretical implications are discussed. PMID- 1606514 TI - [Purification, amino acid composition and N-terminal sequence of the major protein (protein H) of the outer membrane of Pasteurella multocida]. AB - The major protein (protein H) of the outer membrane of Pasteurella multocida was purified by size-exclusion chromatography after selective extraction with detergents. The protein forms homotrimers which are stable in the presence of SDS at room temperature. Upon treatment at 100 degrees C, the protein is fully dissociated by the detergent into monomers exhibiting an apparent molecular mass of 37 kDa as estimated by electrophoresis. The amino acid composition of protein H is characterized by a low hydropathy index (HI = -0.40) and is strongly related to the compositions of bacterial porins, notably porins P2 (Haemophilus influenzae), PIA (Neisseria gonorrhoeae) and Cl.2 ("class 2 porin" of N. meningitidis). The N-terminal amino acid sequence of protein H shares a strong homology with those of porins OmpC (Escherichia coli) and P2. These data indicate that protein H of P. multocida is a porin belonging to the superfamily of the non specific porins of Gram-negative eubacteria outer membrane. PMID- 1606515 TI - [Increase in the pace of the growth of the human fetus towards the end of pregnancy]. AB - Growth velocity curves of 19 biometrical parameters were established from 490 normal fetuses or neonates, who died in the perinatal period, and from 4,507 ultrasound examinations. There was a velocity fall for numerous parameters during the third trimester of gestation, but growth rate started up again after 38 weeks for some of them (femur length, biparietal diameter, crown-rump length, head circumference ...). No acceleration was found for body weight and crown-heel length by the end of gestation. PMID- 1606516 TI - Home care for the terminally ill. PMID- 1606517 TI - Clinical use of immune serum globulin as replacement therapy in patients with primary immunodeficiency syndromes. AB - IVIG is the definitive therapy for primary immunodeficiency diseases associated with hypogammaglobulinemia or specific antibody deficiencies. Administration of IVIG is relatively safe, but occasional adverse reactions are usually self limited and generally are not an indication for stopping therapy. Home administration of IVIG has found increasing favor among treating physicians and their patients. PMID- 1606518 TI - IVIG therapy today. PMID- 1606519 TI - The role of IVIG in the management of patients with antiphospholipid antibodies and recurrent pregnancy losses. AB - Intravenous immune gamma-globulin appears to have a role in the management of some autoimmune-mediated diseases. The exact mechanisms whereby IVIG is beneficial to patients with these diseases are not understood. The antiphospholipid-antibody syndrome is a recently recognized syndrome in which antibodies to negatively charged phospholipids are associated with a thrombotic diathesis, fetal wastage, and thrombocytopenia. The association between these antibodies and the clinical complaints is unknown. Recent evidence has suggested that a cofactor, a serum protein or glycoprotein (of approx 50 kDa) is essential for so-called antiphospholipid antibodies to bind to phospholipids. It may be that variations in this cofactor and its binding are some of the factors that determine whether high levels of antiphospholipid antibodies result in pathological consequences. Patients with antiphospholipid antibodies who have experienced previous fetal losses will continue to experience fetal wastage without some form of therapeutic intervention. The optimum therapy for these patients is yet to be determined, but recent isolated anecdotal reports suggest that IVIG may be of some benefit. IVIG appears to be less toxic to the mother than prednisone. The true benefit of IVIG, however, can be determined only by randomized, well controlled trials. Adequate numbers of patients could only be obtained by multicenter studies, and these should be designed to compare anticoagulation alone with anticoagulation and IVIG. Justifying a placebo group is difficult, as it is known that greater than 90% of pregnancies in women with aPL who have previously experienced fetal wastage fail to produce a live infant. It is only by doing such studies that the true role of IVIG in the management of pregnant patients with aPL can be determined. PMID- 1606520 TI - Current status of intravenous immunoglobulin in preventing or treating neonatal bacterial infections. PMID- 1606521 TI - Asthma. A role for IVIG therapy? AB - Asthma is a multifactorial, reversible, obstructive lung disease that manifests airway inflammation as well as airway hyperreactivity. In addition to IgE mediated respiratory reactions, the pathophysiology of asthma can be triggered by both viral respiratory and bacterial sinopulmonary infections. Even though most asthma patients do not manifest undue susceptibility to infection, a subset of asthma patients with recurrent sinopulmonary as well as upper-respiratory infections may have an associated immune deficiency syndrome. In a subset of these patients, deficiencies of serum IgG subclasses have also been described in the presence of low-normal or normal serum IgG and also deficient serum IgA. In addition to the usual asthma therapy with beta 2 agonist and theophylline bronchodilators as well as cromolyn and steroids, many of these immunodeficiency patients will benefit from iv gamma-globulin therapy. However, we suggest that an inability to synthesize specific serum antibody to injected vaccines or immunogens be a prerequisite before initiating iv gamma-globulin therapy. The clinician should not rely on serum IgG subclass levels alone as a criterion for initiation of passive immune globulin therapy. There may be another cohort of asthma patients who could benefit from iv gamma-globulin therapy. In a small open label pilot study severe steroid-dependent asthma patients who were not immunodeficient and did not have undue susceptibility to infection were treated with iv gamma-globulin with a very large dosage protocol of 2000 mg/kg monthly.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606522 TI - The potential use of monoclonal antibodies as therapeutic modalities in neonatal infection. PMID- 1606523 TI - Immune deficiencies in chronic lymphocytic leukemia and multiple myeloma. PMID- 1606524 TI - IVIG in the treatment of children with acute and chronic idiopathic thrombocytopenic purpura and the autoimmune cytopenias. AB - IVIG has been shown to be useful in the treatment of acute and chronic ITP, immune neutropenia, and in some cases of AIHA. The mechanism of action of IVIG is owing to a number of factors, which include Fc blockade, immune modulation of T- and B-cell number and function, alterations in NK activity, and direct effects on autoantibody binding and production via the antiidiotypic antibody network. Current research efforts are directed toward elucidation of these modalities and determination of their relative importance in treating patients with immune mediated cytopenias. PMID- 1606525 TI - IVIG therapy in neonatal isoimmune thrombocytopenic purpura and alloimmunization thrombocytopenia. PMID- 1606526 TI - The clinical efficacy of IVGG in Kawasaki disease. PMID- 1606527 TI - The immunoregulatory effects of IVIG in Kawasaki disease and other autoimmune diseases. PMID- 1606528 TI - Stereologic, histopathologic, flow cytometric, and clinical parameters in the prognostic evaluation of 74 patients with intraoral squamous cell carcinomas. AB - BACKGROUND AND METHODS: A consecutive series of all 78 incident cases of intraoral squamous cell carcinoma occurring during a 2-year period in a population of 1.4 million inhabitants were evaluated by histologic score (the modified classification of Jacobsson et al.), flow cytometry, stereology, tumor size, and the TNM classification. RESULTS: The investigation showed a significant difference between the volume-weighted mean nuclear volume (nuclear vv) of oral leukoplakia (n = 29) and oral squamous cell carcinomas (P = 0.001). The value of the parameters as prognostic indicators of survival and recurrence was tested with Kaplan-Meier plots and Cox multiple hazard regression analysis. Tumor size, T-stage, stereologically estimated nuclear vv, and mean nuclear profile area were all of significant prognostic value in single factor analysis with reference to both survival and recurrence. The histologic parameters of mitotic activity, morphologic nuclear dedifferentiation, and histologic mean malignancy score and the DNA ploidy level had no prognostic value. A prognostic index based on the results of the Cox analysis that included T-stage and nuclear vv was correlated highly with survival (P = 0.00001) and recurrence (P = 0.002). CONCLUSION: These findings may contribute to optimal and individualized therapy. PMID- 1606529 TI - Clonal evolution in primary 5q-syndrome. AB - Primary 5q-syndrome is a type of myelodysplastic syndrome characterized by refractory anemia, thrombocytosis, and hypolobulated megakaryocytes. The risk of leukemic transformation is low. A case of 5q- syndrome that occurred in a 42-year old woman and was complicated by leukemic transformation 7 years after the initial diagnosis is reported. An additional clonal karyotypic anomaly, del(7q), was seen in the leukemic cells. The literature on leukemic and karyotypic evolution of primary 5q- syndrome is reviewed and the implication of karyotypic evolution is discussed. PMID- 1606530 TI - Basal cell carcinoma. An epidemiologic study in a defined population. AB - BACKGROUND: The incidence of basal cell carcinoma (BCC) in a defined population is unknown. METHODS: The incidence of histologically diagnosed cases of BCC in a defined population of a city in southern Sweden was studied. Four 2-year periods were examined from 1970 to 1986. Cases from 1970 and 1980 were reexamined microscopically. RESULTS: From 1970 to 1986, the age-standardized incidence of BCC was doubled. BCC was equally common in male and female patients. It was possible to trace another BCC in the medical history of 41% of the patients. The risk of development of BCC increased rapidly with age greater than 55 years. Approximately two-thirds of the tumors were found in the head and neck region. There was a possible increase in superficial multicentric tumors on the trunk but otherwise an essentially unchanged pattern in type and distribution. CONCLUSIONS: The age-standardized incidence of histologically diagnosed BCC was doubled from 1970 to 1986. The rapid increase should be taken into consideration when planning allocation of medical resources. PMID- 1606531 TI - Significance of aneuploidy in melanoma of the extremity. AB - Tumor nuclear DNA content was determined by flow cytometry in routinely prepared paraffin blocks from 25 primary malignant melanomas of the extremities. Twelve of the tumors were aneuploid, and 13 were euploid. In this series the presence of aneuploidy appeared to have no prognostic value. PMID- 1606532 TI - Soft tissue leiomyosarcoma. A population-based epidemiologic and prognostic study of 48 patients, including cellular DNA content. AB - BACKGROUND: Leiomyosarcoma of soft tissue is a rare tumor. There are different opinions regarding epidemiology and prognosis. METHODS: Epidemiology and prognosis were analyzed in a consecutive, population-based series of 48 patients with subcutaneous and deep-seated leiomyosarcoma in the extremities and trunk wall with a complete follow-up of a minimum of 3 years. Cutaneous tumors were not included. RESULTS: The annual incidence was 0.13/10(5). The ratio of men to women was 1.2, and the median age was 65 years. The thigh was the most common location. Almost half of the tumors were subcutaneous. The median tumor size was 6 cm (range, 1-25 cm). All patients were treated with surgery, and in 19 cases it was combined with adjuvant radiation therapy or chemotherapy. The cumulative 5-year survival rate was 64%. Multivariate analysis indicated that age of 60 years or greater (relative risk [RR] = 8) and intratumoral vascular invasion (RR = 4) were independent risk factors for death resulting from tumor. DNA aneuploidy (RR = 4) and tumor necrosis (RR = 3) were associated with poor prognosis, but did not reach statistic significance. CONCLUSIONS: Advanced age, vascular invasion, and DNA aneuploidy could be used to identify prognostic subgroups. PMID- 1606533 TI - Psychological distress after initial treatment of breast cancer. Assessment of potential risk factors. AB - BACKGROUND: Patient and disease characteristics are often mentioned by clinicians as possible risk factors for psychological distress among women with breast cancer. However, either these factors have not been evaluated or when they were evaluated, results were inconclusive. METHODS: Potential risk factors for psychological distress were assessed among 205 patients with newly diagnosed breast cancer by home interview 3 and 18 months after surgery. RESULTS: At 3 months, proportions of women with high distress reporting 0-1, 2-3, 4-5, and 6-15 stressful life events in the 5 years preceding diagnosis were 17%, 20%, 28%, and 37%, respectively (P = 0.006). High levels of psychological distress were present in 63.1% of women with a history of depression, compared with 14.3% of those with no such history (P = 0.0001). Associations of these factors with distress also were present 18 months after diagnosis. At 18 months only, distress was more frequent in women with regional disease (44%) than in those with localized disease (22%) (P = 0.006). Age, education, and marital status had little or no association with levels of psychological distress. CONCLUSIONS: Number of stressful life events before diagnosis and history of depression appear to be strong indicators of the risk of psychological distress and may be useful for identifying patients with breast cancer in need or more intense psychosocial support. PMID- 1606534 TI - A case of juvenile papillomatosis of the male breast. AB - BACKGROUND: Juvenile papillomatosis is a proliferative epithelial lesion of the female breast, and Rosen et al. introduced it in 1980 as an entity. RESULTS: The authors present a case consistent with juvenile papillomatosis of the male breast, occurring in a 33-year-old man, who had noticed a swelling of his right breast for approximately 17 years. On review of the literature regarding epithelial proliferations of the male breast, the authors found three cases with similar histologic features. CONCLUSIONS: The case studied indicates a benign behavior of this lesion in the male breast, although no data concerning long-term prognosis are available. PMID- 1606535 TI - Survival after first recurrence of breast cancer. The Miami experience. AB - BACKGROUND: Four hundred thirty-three patients with recurrent breast cancer were treated by the authors at a large medical breast oncology facility from 1976 1982. The median survival time from first relapse (MSFR) for the 193 patients whose survival experience was not confounded by lead-time bias was 26 months. This MSFR is similar to that of most series published in the 1970s and 1980s and is approximately double that of series published in the 1960s. METHODS: In this series, regression analysis identified disease-free interval (DFI), estrogen receptor (ER) status, and dominant disease site as significant prognostic variables, similar to other published series. RESULTS: In 113 patients with known ER values, DFI, and dominant metastatic sites, a prognostic spectrum of MSFR patterns was identified among combinations of these three variables. The MSFR ranged from 15 months for poor risk patients with negative ER values, visceral dominant sites, and DFI of less than 24 months, to more than 90 months for good risk patients with positive ER values, soft tissue dominant sites, and DFI of more than 24 months. Although menopausal status alone was not a significant prognostic variable in regression analysis, 66% of premenopausal patients had a constellation of "poor" prognostic variables. CONCLUSIONS: This type of prognostic factor analysis at first relapse could help identify subsets of patients who might be considered for aggressive investigational therapies such as high-dose chemotherapy with autologous bone marrow reconstitution. PMID- 1606536 TI - Second primary tumors in patients with oral cancer. AB - BACKGROUND: Patients with cancer of the oral cavity and pharynx have been described to be particularly susceptible to the development of new cancers. METHODS: Using data collected during 1973-1987 by nine population-based cancer registries in the United States, the authors evaluated risks of second primary cancers among 21,371 patients in whom oral and pharyngeal cancers were diagnosed. RESULTS: The rate of development of second tumors was 3.7% per year. The risk of a second primary cancer was 2.8 times greater than expected, with 20-fold excesses of second oral or esophageal cancers and 4-fold to 7-fold increases of respiratory cancers. Increased risks persisted unabated for cancers diagnosed 5 or more years after oral cancer, suggesting that the second cancers were new primary tumors and not misdiagnosed metastases. The increased risks of second primary tumors were found among both men and women and black and white patients; they were most prominent among patients who were 60 years or younger. CONCLUSIONS: The exceptionally high rate of cancer recurrence among patients with oral cancer (exceeding that for all other cancers) points to the need for close medical surveillance. Special emphasis should be placed on advising patients to avoid or limit consumption of tobacco and alcohol, the main risk factors for oral and most second cancers. PMID- 1606537 TI - Serous borderline tumors of the ovary. A clinicopathologic, immunohistochemical, and quantitative study of 44 cases. AB - The clinicopathologic features of 44 serous borderline tumors (SBT) of the ovary were evaluated. Nineteen were Stages II and III, and 9 had invasive peritoneal implants. All 19 patients received chemotherapy and 4, who had invasive implants, died of disease after 3, 4.3, 8, and 9 years. The other 25 patients were free of tumor 1-14 years (mean, 5.3 years) after surgery. Coexpression of low molecular weight keratins (AE1, CAM 5.2) and vimentin was found in all tumors and their implants. No significant differences were found between SBT with different volume corrected mitotic indices (M/Vi) with respect to gross features, presence or absence of implants, stage, and survival. Cytometric DNA analysis also was performed on the primary ovarian tumors and the implants. Twenty-one primary tumors had diploid or tetraploid histograms, and 23 had aneuploid histograms. DNA ploidy of the primary ovarian tumors did not correlate with gross features, the presence or absence of implants, M/Vi, stage, and survival. The data from this study confirm that most SBT are clinically benign, but SBT with invasive implants may behave aggressively. Expression of intermediate filaments, M/Vi, and DNA ploidy evaluation of the primary ovarian tumors seem to be of no value in predicting prognosis. However, four of seven patients with aneuploid DNA implants died of tumor. PMID- 1606538 TI - Use of nuclear morphometry, gleason histologic scoring, clinical stage, and age to predict disease-free survival among patients with prostate cancer. AB - BACKGROUND: Currently, there are no accurate methods for predicting metastases or time to disease progression for patients with clinically localized prostate cancer after surgery. METHODS: In this report, histologic sections were studied from prostate cancer specimens from 100 men with clinically localized prostate cancer (clinical Stages A1 [9 cases], A2 [24 cases], B1 [27 cases], and B2 [40 cases]; pathologic Stages A1 [9 cases], A2 [22 cases], B [23 cases], C1 [8 cases], and D1 [38 cases]) to determine whether nuclear morphometry--when analyzed with clinical stage, pathologic parameters, and age in a multivariate fashion--would predict time to disease progression. RESULTS: These patients were treated with surgery alone for their clinically localized disease and were observed after surgery until disease progression or death. For each of the 100 specimens, 16 different mathematical descriptors described the shape of 150 nuclei. A series of 17 different statistical measurements were calculated to accurately describe the distribution, extremes, and variability within each descriptor. As univariate predictors, the variance of nuclear roundness, the mean of ellipticity, the Gleason score, age, and clinical stage were statistically significant predictors of disease progression when analyzed with Kaplan-Meier survival curves. A prognostic factor score calculated with multivariate analysis of clinical stage, Gleason score, age, and variance of nuclear roundness separated the patients into three statistically distinct groups and predicted time to progression by the Kaplan-Meier life table and Cox proportional hazards analysis. CONCLUSIONS: This prognostic factor score may aid in stratifying patients into high-risk and low-risk groups for testing adjuvant therapies for prostate cancer. PMID- 1606539 TI - Sarcomas of the head and neck. Prognostic factors and treatment strategies. AB - The authors reviewed 164 cases of head and neck sarcoma from adult patients seen at the University of California, Los Angeles (UCLA), between 1955 and 1988. The median follow-up was 70 months. Multivariate analysis demonstrated that tumor grade, size, and surgical margin status were the most important independent prognostic factors. Thirty-one percent (27 of 85) of patients with high-grade lesions were free of disease versus 81% (44 of 55) with low-grade lesions at last follow-up. Sixty-seven percent (50 of 76) of patients with lesions smaller than 5 cm were free of disease versus 38% (33 of 88) with lesions larger than 5 cm. In 16 patients, low-grade lesions, measuring less than 5 cm and with negative margins histologically, were controlled with surgery alone. For the 94 patients whose primary tumors were treated at UCLA, local control was achieved in 52% (26 of 50) of patients treated with surgery alone and 90% (20 of 22) with combined therapy (surgery and radiation therapy [RT] with or without chemotherapy). Seventy-five percent (6 of 8) of patients with positive surgical margins treated with postoperative RT achieved local control versus 26% (5 of 19) of patients receiving no additional treatment. In conclusion, surgery alone appears to be adequate treatment for small, low-grade tumors and negative surgical margins. Patients with incomplete resection or high-grade tumors should receive aggressive treatment--surgery and RT. PMID- 1606540 TI - Types and causes of pain in cancer of the head and neck. AB - In a series of 25 patients with head and neck cancer who had severe pain, the type and cause of the pain were analyzed. There were two types of pain: nociceptive and non-nociceptive. Nineteen (76%) patients had nociceptive pain that could be subdivided into actual nociceptive pain (9 patients), nociceptive nerve pain (8 patients), or referred pain (2 patients). The cause of nociceptive pain was secondary to tumor recurrence in 16 patients and secondary to benign inflammation in 3 patients. Of the six (23%) cases of non-nociceptive pain, all were diagnosed as neuropathic pain secondary to the sequels of neck dissection. World Health Organization guidelines were applied for the treatment of symptomatic pain of nociceptive pain; if necessary, nerve blocks were used after this treatment. Non-nociceptive pain was usually treated with amitriptyline or carbamazepine. If tumor recurrence was the cause of the pain, antitumor-directed therapy was applied, when possible. Relief was achieved in 52% of the patients after two attempts to treat pain, in 64% after three attempts, and in up to 72% after four attempts. Pain could not be controlled in 28% of the patients. Patients with tumor recurrence had a short median survival time of 3 months, regardless of pain control. Patients with neuropathic pain had a survival time of 16 months or more (median not reached). The authors conclude that the type and cause of the pain in cancer of the head and neck can be determined; this can lead to the administration of proper symptomatic therapy or treatment directed at the underlying cause. In most cases, several successive attempts to treat pain were made before relief was achieved. PMID- 1606541 TI - Clinical implications of learned food aversions in patients with cancer treated with chemotherapy or radiation therapy. AB - BACKGROUND: The nutritional implications of learned food aversions were evaluated in patients with newly diagnosed cancer receiving either chemotherapy (n = 53) or radiation therapy (n = 49). METHODS: Aversion incidence was determined by questionnaires and a food challenge. Measures of dietary and nutritional status included ratings of appetite and chemosensory function; reported shifts of food selection and measured body weight; lymphocyte count; hematocrit; and plasma albumin, transferrin, and hemoglobin levels. Quality of life was assessed by self ratings of mood and well-being. RESULTS: Subsequent to the initiation of treatments, aversions formed in 56% and 62% of patients receiving chemotherapy and radiation therapy, respectively. The aversions were specific (two to four items per afflicted patient) and transient (mean duration, 0.25-2 months). All types of foods and beverages were targeted. No significant association was observed between food aversion incidence and any measure of dietary complications, nutritional status, or quality of life. CONCLUSIONS: Although food aversions are a common sequela of chemotherapy and radiation therapy, they generally have limited clinical significance. PMID- 1606542 TI - Simultaneous assay of adenosine deaminase and purine nucleoside phosphorylase activity as possible biochemical means to detect non-Hodgkin lymphomas of the oral cavity. AB - BACKGROUND AND METHODS: This study proposes the usefulness of simultaneous assay of adenosine deaminase (enzyme code [EC] 3.5.4.4; ADA) and purine nucleoside phosphorylase (EC 2.4.2.1; PNP) activities in a biopsy specimen as a biochemical test adjunctive to the histologic diagnosis of oral non-Hodgkin lymphomas (NHL). RESULTS: NHL tissues showed an ADA activity of more than 1428 nmol/h/mg of protein, and more than 3451 nmol/h/mg of protein was the sum of ADA and PNP activity. In contrast to this finding, all the 106 lesional tissues affected by various carcinomas, various benign tumors, various cysts, ameloblastomas, osteosarcomas, gingival hyperplasia, and inflammation showed an ADA activity of less than 1000 nmol/h/mg of protein, except for 2. The sum of ADA and PNP activity was less than 2249 nmol/h/mg of protein in these diseases, except for squamous carcinoma. Different control tissues of the oral cavity showed less than 766 nmol/h/mg of protein in ADA activity, and the highest sum of ADA and PNP activity in these was only 1384 nmol/h/mg of protein. CONCLUSIONS: These findings suggest that a strong suspicion of oral NHL is justified when the sum of ADA and PNP activity in a biopsy specimen exceeds 3000 nmol/h/mg of protein and ADA activity is greater than 1000 nmol/h/mg of protein. PMID- 1606543 TI - Allergic reactions to Erwinia asparaginase in children with acute lymphoblastic leukemia who had previous allergic reactions to Escherichia coli asparaginase. AB - BACKGROUND: Escherichia coli asparaginase is an active antileukemia agent in the treatment of childhood acute lymphoblastic leukemia. Allergic reactions occurred in 31 of 125 patients (24.8%) treated with weekly high-dose (25,000 IU/m2) intramuscular E. coli asparaginase and necessitated discontinuation of the drug. METHODS: The authors evaluated the toxic effects of Erwinia asparaginase in the 31 children who had allergic reactions to the E. coli preparation. RESULTS: Subsequent allergic reactions to Erwinia asparaginase occurred in 7 of the 31 children (22.6%). In contrast to previous reports with intravenous administration, most allergic reactions to both asparaginase preparations were characterized by mild urticaria that responded to use of diphenhydramine; none of the reactions was life-threatening. CONCLUSIONS: In summary, the authors found Erwinia asparaginase to be an acceptable substitute for E. coli asparaginase for most children who had allergic reactions. Through the use of both E. coli and Erwinia asparaginase, 94% of children could receive their intended asparaginase. PMID- 1606544 TI - Hepatic resections for colorectal metastases in The Netherlands. A multiinstitutional 10-year study. AB - BACKGROUND AND METHODS: The records of 118 patients who had hepatic resections for colorectal liver metastases were analyzed retrospectively. RESULTS: The patient group, from 15 institutions in The Netherlands, was found to have a 5 year actuarial survival rate of 21% and a 5-year actuarial disease-free survival rate of 19%. The postoperative mortality rate was 7.6%. In the remaining group, the morbidity rate was 34.7%. A number of factors were examined that were reported to be of prospective significance in other studies. In the multivariate proportional hazard model of Cox, the number of metastases (P = 0.001) and the amount of perioperative blood loss (P = 0.002) were related significantly to disease-free survival. A factor that may be considered a contraindication to resection is the presence of extrahepatic disease (whether nodal or visceral), even if resectable. CONCLUSIONS: Although the actual benefit of resection is limited, and it is associated with considerable morbidity, surgical therapy offers some patients a chance for cure. It is a valid expectation that improvement in techniques and a proper understanding of hepatic anatomy will improve the safety and efficacy of hepatic resections in the future. Future research should focus on defining better selection criteria and on study of the value of adjuvant treatment modalities. PMID- 1606545 TI - The utility of squamous cell carcinoma antigen for the follow-up of patients with squamous cell carcinoma of the anal canal. AB - BACKGROUND: Thirty-three patients with histologic documentation of squamous cell carcinoma (SCC) of the anal canal underwent prospective serial collection of 234 serum samples for radioimmunoassay of SCC tumor-associated antigen. METHODS: There were 23 female and 10 male patients, with a median age of 55 years. Twenty two of the 33 patients had multimodality therapy with radiation therapy and chemotherapy as initial treatment. RESULTS: The median follow-up was 22 months (range, 4-52 months), with a median of 13 serum specimens per patient (range, 1 23 specimens). Twenty-eight patients currently have no evidence of disease, 4 patients are alive with disease, and 1 patient died with disease. CONCLUSION: In these 33 patients, the sensitivity of the SCC tumor-associated antigen was 76%, specificity 86%, and positive predictive value 62%. PMID- 1606546 TI - Family history and the risk of stomach and colorectal cancer. AB - BACKGROUND: The role of a family history of selected neoplasms in first-degree relatives in the risk of gastrointestinal cancers has been investigated, but requires further quantification. METHODS: A case-control study was conducted in northern Italy on 628 histologically confirmed incident cases of stomach cancer, 766 cases of colon cancer, 456 cases of rectal cancer, and 1766 controls admitted to hospital for acute, nonneoplastic, non-digestive tract disorders. RESULTS: Significant associations were observed between a family history of gastric cancer and stomach cancer risk (relative risk [RR], 2.6), and between a family history of intestinal cancer and colon (RR, 2.4) and rectal cancer (RR, 1.7). There was a tendency for the risks to be above unity for a family history of stomach cancer and for a number of other cancer sites (including esophagus, intestines, liver, pancreas, gallbladder, and lung), and the RR were of borderline statistical significance for cancer of the liver and intestines. The RR for a family history of lung cancer was 1.5 for stomach, 1.2 for colon, and 1.3 for rectal cancer, with none of the estimates being significant. There was no consistent pattern of risk with reference to the type of first-degree relationship; the RR was similar for stomach cancer with reference to parents and siblings, and for colon and rectal cancer, it was only moderately higher with reference to siblings. Significant trends in risk with the number of first-degree relatives were observed for all three cancer sites investigated. CONCLUSIONS: In terms of population attributable risk, approximately 8% of stomach cancers and 3% of colorectal cancers would be related to this familial component. PMID- 1606547 TI - DNA content and histologic growth pattern correlate with prognosis in patients with advanced squamous cell carcinoma of the larynx. The Department of Veterans Affairs Cooperative Laryngeal Cancer Study Group. AB - BACKGROUND: Alterations in DNA content, nuclear morphologic characteristics, and histologic grading have been associated with prognosis in several types of solid malignant neoplasms. METHODS: To determine the potential usefulness of these factors in predicting tumor behavior in patients with laryngeal squamous cell carcinoma, tumor specimens from 88 previously untreated patients with Stage III or IV cancers were studied. The DNA content and nuclear area (NA) were measured for individual nuclei of each tumor with the use of Azure A-stained frozen sections. An adjusted DNA index (aDI) for each patient was calculated from the slope of the linear regression analysis of nuclear DNA index on NA. Hematoxylin and eosinstained sections were examined and graded systematically for histologic growth pattern. All patients were enrolled in a prospective clinical trial and had laryngectomy and postoperative radiation therapy. RESULTS: The disease-free survival length was longer and the relapse rates were lower in patients with a low aDI (P less than 0.005) and with tumors exhibiting low-grade growth patterns (P less than 0.001). CONCLUSIONS: These parameters were independent of staging variables and were better predictors of tumor relapse than traditional clinical staging classifications. PMID- 1606548 TI - Correlation between nucleolar organizer regions visualized by silver staining and the growth rate in lung adenocarcinoma. AB - BACKGROUND: The value of nucleolar organizer regions (NOR) visualized by silver staining (AgNOR) for the histologic differentiation, pathologic staging, and estimation of growth rate was assessed by the investigation of paraffin sections from 58 lung adenocarcinomas. AgNOR consist of NOR-associated proteins, and the number of AgNOR might be related to proliferative activity. METHODS: In lung adenocarcinoma, the growth rate can be measured by means of chest radiographs. Using this technique, the authors studied the correlation between the mean number of AgNOR and growth rate. RESULTS: The mean number of AgNOR ranged from 1.8 to 6.3 (mean +/- standard deviation, 4.0 +/- 0.8). Neither the degree of histologic differentiation nor the pathologic staging was related to the AgNOR count. The tumor growth rate was estimated on the basis of the doubling time in the chest radiographs of 13 patients. The doubling time ranged from 80 to 760 days. There was a high inverse correlation between the AgNOR count and the doubling time (r = -0.910; P less than 0.001). CONCLUSIONS: Thus, it appears to be possible to use the mean number of AgNOR as an index of proliferative activity. PMID- 1606549 TI - Cumulative tar exposure. A new index for estimating lung cancer risk among cigarette smokers. AB - A new index for estimating lifetime exposure to tar from cigarette smoking was found to be the best measure of the relative risk for Kreyberg type I (KI) and Kreyberg type II (KII) lung cancer in a case-control study of 2296 cases (1274 KI and 1022 KII) and 4667 controls. There is a steep, near-linear dose-response of lung cancer risk of both histologic types to cumulative exposure to tar, although the odds ratios are three to five times higher for KI than for KII. The odds ratios for lung cancer in women are consistently higher than those in men with the same level of exposure to tar, particularly among long-term smokers who smoke heavily. Based on their estimates of odds ratios associated with tar exposure, the authors projected an approximate 15-20% decrease in KI lung cancer risk among long-term smokers who smoked heavily for every 10-mg decrease in tar in the cigarettes they smoked. PMID- 1606550 TI - Distinct cytogenetic and clinicopathologic features in acute myeloid leukemia after occupational exposure to pesticides and organic solvents. AB - BACKGROUND: To study the correlation of environmental exposure to potentially mutagenic agents and the clinicopathologic picture in acute myeloid leukemia (AML), clinical features, morphologic characteristics, immunophenotype, and cytogenetics were studied in 59 patients with newly diagnosed AML. METHODS: Based on interviews on occupational hazards and hobbies showing prolonged contact with pesticides (18 patients) and organic solvents (7 patients), 25 patients were categorized as "exposed". Thirty-four patients were categorized as "unexposed,", based on anamnestic findings. RESULTS: Light microscopic studies showed myelodysplasia involving multiple cell lineages in all assessable patients with professional exposure to pesticides and organic solvents, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in unexposed patients. These findings were confirmed by electron microscopic studies in 31 patients. Immunologic analysis showed the presence of a minor megakaryoblastic component in six exposed patients and showed positive findings for the CD34 stem cell marker in 85% of exposed patients, a figure significantly higher as compared with that for unexposed subjects. Cytogenetic studies confirmed the frequent occurrence of 5q and/or 7q aberrations in patients occupationally exposed (10 of 25 cases). Other recurring chromosome aberrations in the exposed group were 17p-, trisomy 11q, and translocation of 16q, 6p, 7p, and 11p, whereas the classic AML-specific translocations (i.e., t[15;17]; t[8;21]) were detected only in unexposed subjects. Conventional chemotherapy achieved complete remission in 1 of 19 exposed patients, as opposed to 14 of 29 unexposed patients, with a median survival of 2 months in the former group and 8 months in the latter. CONCLUSIONS: Taken together, these findings document that AML in patients professionally exposed to toxic substances may represent a distinct cytogenetic and clinicopathologic entity. The clinicobiologic characteristics in these exposed patients are similar to the features of AML arising in patients with prior chemotherapy for another tumor, thus suggesting that similar transformation pathways may underlie leukemogenesis induced by cytotoxic drugs and by environmental exposure to some pesticides or organic solvents. PMID- 1606551 TI - T-cell chronic lymphocytic leukemia. Unusual morphologic, phenotypic, and karyotypic features in association with light chain amyloidosis. AB - BACKGROUND: Lymphocytes that display a phenotype of mature B-cells, T-cells, natural killer (NK) cells, or a combination of T-cells and NK cells can be found in patients with lymphoproliferations that manifest as expansions of peripheral blood lymphocytes (PBL). If these PBL expansions exhibit clonality, they can be classified as chronic lymphocytic leukemia (CLL). METHODS/RESULTS: A patient who had two simultaneous, clonal lymphoproliferative disorders manifested as an unusual T-cell CLL in conjunction with systemic light chain amyloidosis is described. Gene rearrangement studies of the PBL of the patient showed clonal rearrangements of both the T-cell receptor beta (T beta) chain and the immunoglobulin genes. Additional immunologic and microscopic studies of the T cells of the patient showed that they were large, agranular, CD4+ T-cells that also expressed the NK cell marker CD57. Cytogenetics disclosed an unusual karyotype in the PBL. CONCLUSIONS: The pathogenesis of this T-cell CLL and whether it truly represents a malignant disorder, as well as its relation to amyloidosis, is discussed. PMID- 1606552 TI - Cytogenetic and clinical findings of myelodysplastic syndromes with a poor prognosis. An experience with 97 cases. AB - BACKGROUND: Clinical and cytogenetic analyses were performed in 97 patients with myelodysplastic syndromes (MDS) to evaluate risk factors for poor prognosis. METHODS/RESULTS: Among them, 22 patients survived for less than 1 year: 10 of these had complex chromosomal abnormalities (complex aberrations), but only 5 of the remaining 75 patients who survived longer than 12 months did. Leukemia did not develop in approximately half of the patients who died within 1 year. The occurrence rate of leukemic transformation appears to depend on MDS subtypes rather than cytogenetic changes. In contrast, the percentage of patients who survived for less than 1 year is related to chromosomal changes, especially to complex aberrations. Of particular interest in this study is that 7 of 11 patients with MDS who had myelofibrosis survived for less than 1 year, and 5 of 7 patients with secondary MDS were included in this group showing a poor prognosis. By hematologic analysis, significant differences were found in the hemoglobin values and platelet counts of patients who survived for less than 1 year. CONCLUSIONS: From this analysis, three major risk factors for a poor prognosis were identified: complex aberrations, a history of chemotherapy or radiation therapy (secondary MDS), and development of myelofibrosis. The survival probability in the patients with MDS having at least one of these three factors was significantly low when compared with that in patients without these factors, indicating that cytogenetic analysis in combination with observance of certain clinical manifestations is important in therapeutic management of patients with MDS. PMID- 1606553 TI - Skin cancer and chromosomal aberrations induced by ultraviolet radiation. Evidence for lack of correlation in xeroderma pigmentosum variant and group E patients. AB - Ultraviolet radiation (UV) in sunlight induces an abnormally high incidence of skin cancer in patients with xeroderma pigmentosum (XP), an autosomal recessive disease with defects in the repair of damaged DNA. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblast lines from a patient with the variant form of XP, from a patient with the complementation group E form, and from two patients with the complementation group C form. In contrast to results with patients having other forms of XP, the group E and variant patients showed no abnormal increase in UV-induced chromosomal aberrations. Even in the presence of caffeine, which exacerbates the postreplication repair defect of UV irradiated XP variant cells, there was still no abnormally elevated frequency of UV-induced chromosomal aberrations in the variant cells. These results, indicating that the level of UV-induced chromosomal aberrations is not correlated with these patients' marked susceptibility to skin cancer, suggests that some mechanism other than genetic transposition is causatively related to these XP patients' high incidence of sunlight-induced skin cancer. PMID- 1606554 TI - Cytogenetic studies in acute nonlymphocytic leukemia. AB - Cytogenetic studies were performed in 74 untreated patients with acute nonlymphocytic leukemia (ANLL) between 1985 and 1988. Among 56 patients who were examined successfully at the time of diagnosis, 36 had abnormal karyotypes (64.2%). The distribution of chromosome abnormalities was uneven, according to the categories of the French-American-British (FAB) nomenclature. The highest frequency of chromosome abnormalities was observed in ANLL M4 with bone marrow (BM) eosinophilia (M4Eo). Numerical changes were observed in 11 cases; chromosome 8 was most frequently gained (11 patients), whereas chromosome 7 was most frequently lost (4 patients). Structural rearrangements were detected in 18 patients. Involvement of 16q22 was noted in 7 patients, 5q- was noted in 5, t(8;21) in 3, t(1;7) in 2, del(20) in 2, and involvement of 11q23 was noted in 2. The inversion of chromosome 16 was restricted to the M4Eo subtype. This study identified a novel abnormality [inv(2) (p11.2q11.2)] that had not been reported previously by other investigators. PMID- 1606555 TI - New chromosomal abnormality. t(1;19;?) in a case of B-chronic lymphocytic leukemia. AB - Cytogenetic analysis was performed on peripheral blood cells stimulated with interleukin 6 (IL-6), lipopolysaccharide from Escherichia coli (LPS), phytohemagglutinin (PHA), pokeweed mitogen (PWM) and tetradecanoyl-phorbol acetate (TPA), in a patient with B-chronic lymphocytic leukemia, showing a t(1;19;?) translocation as the sole abnormality. To our knowledge, this translocation has not been described before in any human neoplasia. In this case, the poor response to therapy (survival time 4 months) suggested that t(1;19;?) could be related to an aggressive course of the disease. PMID- 1606557 TI - Lentigo maligna. Cytogenetic, ultrastructural, and phenotypic characterization of a primary cell culture. AB - Lentigo maligna is an early cutaneous neoplastic lesion. This article presents the cytogenetic, ultrastructural, and phenotypic characterization of a primary cell culture obtained from a patient affected with lentigo maligna. Two cellular clones were identified, both characterized by chromosomal markers involving chromosome 10 with a breakpoint at 10q26. PMID- 1606556 TI - 12q13 abnormality in rhabdomyosarcoma. A nonrandom occurrence? AB - We describe two cases of rhabdomyosarcoma with a translocation involving 12q13 as the primary cytogenetic abnormality. Literature review of 35 cases has identified 3 other cases with this abnormality, and we speculate that this may be another nonrandom rearrangement in rhabdomyosarcoma. PMID- 1606558 TI - Telomeric associations evolving to ring chromosomes in a recurrent pleomorphic xanthoastrocytoma. AB - Telomeric associations observed in a recurrent untreated pleomorphic xanthoastrocytoma were apparently the primary cytogenetic events that evolved by fusion and breakage events, resulting in subclones with ring chromosomes. The telomeric fusions between chromosomes 15pter and 20qter, and between an extra copy of the long arm of chromosome 1 and chromosome 22qter, evolved in a stepwise fashion to ring chromosomes 20 and 22. The findings in this tumor demonstrate that telomeric association is one mechanism that can initiate chromosome instability by generating subclones with unstable chromosome intermediates and result in ring chromosomes and subsequent chromosome loss. PMID- 1606559 TI - Cytogenetic analysis in ataxia telangiectasia with malignant lymphoma. AB - We present the results of cytogenetic analysis in a brother and sister with ataxia telangiectasia (AT), one of whom had malignant T-cell lymphoma. In both children, cytogenetic analysis of phytohemagglutinin (PHA)-stimulated lymphocytes showed chromosomal instability and inv(7) in 10% of the cells examined. The malignant lymphoma was analyzed cytogenetically on slides obtained from short term culture of the lymph node cells; 64 cells were analyzed. A heterogeneous cell population was noted. Fourteen cells (21.9%) had a normal male karyotype; t(7;14)(p14;q12) and inv(7)(p14q35) were observed in 6.3% and 3.1% of metaphases. Owing to low frequency, these cells are probably a characteristic of the basic disease and have no features of malignant cells. Forty cells (62.5%) had a pseudodiploid karyotype 46,XY,dup(1)(p22p36),del(5)(q33),del(12)(p11), without cytogenetically evident aberrations of chromosomes 7 and 14. The results of these investigations suggest that the cells with rearrangements of chromosomes 1, 5, and 12 are malignant cells and did not originate by transformation of cells with inv(7) and t(7;14). PMID- 1606560 TI - Malignant melanoma of soft parts. Further cytogenetic characterization. AB - We report the cytogenetic findings in a case of malignant melanoma of soft parts. Overrepresentation of 1q together with a del(1)(q42), extra copies of chromosomes 7 and 8, and t(12;22)(q13;q13) were found. These findings allow further delineation of the chromosomal pattern found in this uncommon neoplasm. PMID- 1606561 TI - Acute monocytic leukemia with (8;22)(p11;q13) translocation. Involvement of 8p11 as in classical t(8;16)(p11;p13). AB - A new case of acute monocytic leukemia observed in a 73-year-old male (ANLLM5) with an unusual t(8;22)(p11;q13) is reported. The blasts did not demonstrate erythrophagocytosis, but the presence of both naphthol-ASD-chloro-acetate esterase and butyrate esterase activities was similar to that seen in cases with t(8;16)(p11;p13). Involvement of the 8p11 region in ANLLM4 and M5 is discussed, being the third most frequent rearrangement in acute leukemia with monocytic components seen at our Center. PMID- 1606562 TI - Screening for cancer genes. PMID- 1606563 TI - Chronic myelomonocytic leukemia with t(13;14) in a child. AB - Bone marrow cells from a child with chronic myelomonocytic leukemia showed an acquired, non-Robertsonian translocation between chromosomes 13 and 14, t(13;14)(q12.?2;q32.?3). This rearrangement has not previously been reported in childhood myeloproliferative or myelodysplastic disorders. PMID- 1606564 TI - A case of adult ALL with +i(13q) as the sole anomaly. AB - A case of ALL with +i(13q) as the sole anomaly in a 77-year-old patient is reported. The clinical and cytogenetic findings are discussed. PMID- 1606566 TI - Embryonal rhabdomyosarcoma with 100 chromosomes but no structural aberrations. AB - An embryonal rhabdomyosarcoma was analyzed cytogenetically after short-term culturing. The tumor was located in the scrotum of an 18-year-old man who, at the age of 4, had been treated for a rhabdomyosarcoma in the orbita. The chromosome number was 100. No structural aberrations were present. There were 2-7 copies of each chromosome type with particular excess of chromosomes 8, 12, and 22, and a relative deficit of chromosome 15. PMID- 1606565 TI - Trisomy 4 in acute nonlymphocytic leukemia. Report of two cases and review of the literature. AB - Two patients with M2 subtype of acute nonlymphocytic leukemia (ANLL) and trisomy 4 as a primary karyotype change are described. The abnormality was observed in 100% of bone marrow (BM) metaphases in both cases. It appeared alone in one case and was associated with trisomy 13 in 94% of metaphases in the other. These are the second and third cases of ANLL with trisomy 4 documented in Italy. Neither patient appears to have incurred any environmental or therapeutic insult. PMID- 1606567 TI - Trisomy 14 in two cases of granulosa cell tumor of the ovary. AB - Cytogenetic analysis of granulosa cell tumor of the ovary was performed in two patients. G-banding analysis of cells cultured 3-5 days showed that the karyotype of each tumor contained normal diploid cells as well as cells with identical aberration: trisomy 14. This is the first report of trisomy 14 in two cases of granulosa cell tumor of the ovary. Flow cytometric DNA content analysis was also performed. PMID- 1606568 TI - Structural rearrangements of chromosome 13 as additional abnormalities in Burkitt lymphoma and type 3 acute lymphoblastic leukemia. AB - We report three cases of chromosome 13 rearrangements as additional abnormalities in two patients with Burkitt lymphoma (BL) and one with type 3 acute lymphoblastic leukemia (ALL). Involvement of chromosome 13 has been reported most often as 13q+, without identification of the supplementary chromosomal material; in our three cases with 13q+, we identified two duplications: dup(13)(q13q22) and dup(13)(q21q22). PMID- 1606569 TI - t(16;21) in a Ph positive CML. PMID- 1606570 TI - Multiple chromosomal abnormalities in a case of craniopharyngioma. PMID- 1606571 TI - i(12p) in a near-diploid mature ovarian teratoma. PMID- 1606572 TI - t(3;6;14)(p21;p21;q24) as the sole clonal chromosome abnormality in a hamartoma of the lung. PMID- 1606573 TI - Outcome of renal transplantation in children aged 1-5 and 6-18 years. AB - Results of renal transplantation in younger children have not been very encouraging in the past. We therefore studied the effect of newer immunosuppressive regimens on the outcome of renal transplantation of 5 children aged 2.9 +/- 1.3 years (range 1.6-5.0), and compared it to 10 children of an older pediatric patient group aged 11.4 +/- 4.4 years (range 6.0-18.5). All patients with the exception of 1 underwent dialysis. The percentage of cadaveric and live-related transplants was similar in both groups. Recipients of a cadaveric transplant had at least 3 blood transfusions; recipients of live related transplants had donor-specific transfusions with azathioprine. Posttransplantation immunosuppression consisted of prednisone and azathioprine; recipients of cadaveric transplants received also ciclosporin. Rejection episodes and side effects (hypertension, hirsutism) were comparable in both groups. In the younger patient group, 1 patient died of a congenital lung abnormality but had a functioning graft. In the older patient group, 1 patient lost his graft 16 months posttransplantation due to reduction of his immunosuppressives, necessitated by a severe CMV infection. Growth and development improved in the younger patient group, but was stable in older patients. Renal transplantation is a suitable option in younger pediatric patients. Graft survival rates are comparable to those of older patients. PMID- 1606574 TI - Effect of corticosteroids on growth in children with steroid-sensitive nephrotic syndrome. AB - The effect on growth of long-term treatment with prednisolone was studied in 12 patients with steroid-sensitive nephrotic syndrome. Our patient's heights were found between the 10th and 25th percentile both at the first and last height measurement. There was no statistical difference between the first and last height standard deviation score (Ht SDS) (p greater than 0.05). When compared with chronological age, growth velocity (GV), GV SDS and bone age were found low but within the normal range for this age group. There was not any correlation between the last Ht SDS and relapse number, total doses and duration of daily and alternate-day steroid therapy (p greater than 0.05). Growth hormone (GH) responses to pharmacological stimuli were obtained as severe deficiency in 10 patients, partial deficiency in 1 patient and normal level in 1. There was statistical difference between the pulse number of the overnight GH profile of the patients and control group (p less than 0.05). But no statistical difference was found between GH pulse amplitude and GH concentration in patients and control group (p greater than 0.05). PMID- 1606575 TI - Urinary excretion of N-acetyl-beta-D-glucosaminidase in proteinuric states. AB - Urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG) was studied in 22 children with proteinuria and a normal glomerular filtration rate. Twelve patients had minimal change nephrotic syndrome (MCNS), 10 children suffered from different types of glomerulonephritis (GN) without tubulointerstitial renal disease. Sixty-six random urine samples were analyzed for protein, creatinine and NAG. There was a strong positive correlation between proteinuria and urinary NAG activity (r = 0.79, p = 0.0001). The raised NAG activities in proteinuric states turned to normal during remission of the disease. Patients with MCNS and GN did not differ significantly and had nearly identical correlation curves. Our results seem to indicate that functional changes in the renal tubular cells probably caused by protein resorption are responsible for this association. Raised NAG activities in proteinuria reflect the activity of the disease but cannot distinguish patients with MCNS and GN. PMID- 1606576 TI - Long-term effect of a protocol for the diagnosis and treatment of urinary tract infection. Working Group for Urinary Tract Infection in Children of the Friuli Venezia Giulia Region (Italy). AB - We evaluated the policy changes of 10 pediatric departments in the Friuli Venezia Giulia region following the implementation of a new protocol for the diagnosis and treatment of urinary tract infection. Clinical data concerning 1,059 infants and children with a first episode of urinary tract infection were recorded in three periods, before (A), during (B), and after (C) implementation of the protocol application. We observed a significant increase in the total number of urinary tract infections (288 in period A, 464 in C) from period A to C, with particular regard to pyelonephritis (36.8% in period A, 64.3% in C). As radiological investigations were carried out more frequently, there was a significant increase in the number of cases of vesicoureteral reflux recorded (from 23 in period A to 76 in period C). Finally, a better therapeutic approach was progressively achieved: errors in the choice of antibiotics and the duration of treatment have been almost completely avoided in period C. In our opinion, these results demonstrate a long-term improvement of pediatricians' awareness of this frequent pediatric pathology and their policies to control it. PMID- 1606577 TI - Age-related changes of urinary urea. Epidemiological study in children from southern Italy living in Cimitile. AB - Urinary urea was measured, under normal living conditions, in children aged 3-16 years, from Cimitile, a small town near Naples in Southern Italy. Urinary urea correlated with age, height, weight, body mass index and body surface area, and was independent from sex. Urinary urea also correlated with urinary creatinine, uric acid, oxalate, sodium and phosphate. Protein intake assessed from urea excretion was 2.66 +/- 0.66 g/kg at 3 years of age and 1.49 +/- 0.31 g/kg at 16 years, and exceeded Italian standards for recommended intake. Also, the height and weight of the children living in Cimitile, with few exceptions, were in excess of national reference standards. PMID- 1606578 TI - Penile compression--a sign of urethral obstruction. AB - Three boys with urethral obstruction are described. To facilitate voiding, each boy compressed the shaft of his penis prior to initiating the urinary stream, a sign previously unreported in association with urethral obstruction. PMID- 1606579 TI - Urothelial tumors of the bladder. AB - Neoplasms originating from the transitional epithelium of the urinary bladder are rare in children. This paper examines the clinical, epidemiological and histopathological characteristics of 3 such cases. The patients were males aged 4, 8 and 14 years at the time of diagnosis. Total painless hematuria was the presenting symptom in all of them. There was no history of previous exposure to dyes or other chemicals, but 1 patient was a systematic cigarette smoker. All tumors were solitary, noninfiltrating, grade 1 neoplasms. Following their local resection, no recurrences were noted 3-8 years postoperatively. This review supports the contention that transitional cell neoplasms of the bladder are less aggressive in children and, therefore, their local management constitutes an adequate therapeutic approach. PMID- 1606580 TI - Multicystic dysplastic kidney: absence of complications in patients treated conservatively. AB - The optimal treatment, surgical or conservative, for multicystic dysplastic kidney (MDK) is still undetermined. We analyzed prospectively the evolution of 12 children with MDK who were managed conservatively. After a mean follow-up of 32 months, the only complication found was an episode of urinary tract infection in 3 patients. Complete involution of MDK was observed in 9 patients (75%), the mean period for sonographical disappearance being 16 months. Infants with MDK should be closely monitored and nephrectomy performed when MDK compresses neighbor organs or hypertension develops. There is no agreement on the best therapeutic approach in patients in whom MDK involution has not occurred after a prudential waiting time still not determined. PMID- 1606581 TI - Digital subtraction radiography in pediatric cystourethrography. AB - Digital subtraction radiography (DSR) was used to evaluate the anatomy and function of the bladder and urethra in 20 children with clinical urinary disturbances deriving from recurrent urinary tract infections. Following image subtraction, a complete study of bladder and urethra morphology and activity before and during voiding was obtained. Furthermore, DSR permitted a reduction in exposure doses given to children compared to conventional film-screen examinations. Results indicate the applicability of this technique for use on a wider scale and suggest its use as an alternative to other diagnostical techniques for the study of this subject. PMID- 1606582 TI - Focal segmental glomerulosclerosis in desquamative interstitial pneumonia. AB - Renal involvement in desquamative interstitial pneumonitis (DIP) manifesting as chronic renal failure has been reported only once. An uncommon disorder in children, DIP has been associated with a variety of systemic disorders and has an immune-mediated pathogenesis. A 16-year-old Black male was diagnosed to have DIP on lung biopsy at the age of 10 months. He was first noted to have proteinuria at age 5 which progressed to nephrotic syndrome by age 13 when the laboratory tests showed elevated IgG, normal serum complement, increased circulating immune complexes and absent anti-GBM antibodies. A percutaneous renal biopsy specimen performed at age 13 revealed focal segmental glomerulosclerosis. Despite prednisone treatment of 2 mg/kg/day for 12 weeks, renal failure progressed requiring hemodialysis. Pulmonary functions, although reduced, remained stable. PMID- 1606583 TI - Idiopathic infantile hypercalcemia: rapid response to treatment with calcitonin. AB - We report on a 7-week-old infant with idiopathic hypercalcemia, hypercalciuria and nephrocalcinosis. At the time of admission, serum concentrations of parathyroid hormone and 1,25(OH)2D3 were found to be inadequately high, and those of calcitonin and 24,25(OH)2D3 too low, relative to the hypercalcemia. Treatment with calcitonin normalized serum calcium concentrations within 4 days, and a 3 week course of thiazides combined with a decreased dietary calcium:phosphorus ratio corrected the hypercalciuria. A repeat profile of the calcium-regulating hormones done at the age of 5.5 months was normal. Based on the clinical course and the hormonal profiles, we hypothesize that the idiopathic infantile hypercalcemia in this patient could have resulted from a generalized maturational delay of calcium homeostasis. Treatment with calcitonin, therefore, seems to be the most appropriate way to control the hypercalcemia. PMID- 1606584 TI - Class IV lupus nephritis associated with Graves' disease. AB - Graves' disease was initially diagnosed in an 11-year-old Chinese boy in March 1989. After regular propylthiouracil (PTU) and thyroxine, he achieved a euthyroid state. Heavy proteinuria with class IV lupus glomerulonephritis, anemia, arthralgia, low serum complement and anti-dsDNA (+) appeared 15 months later. Thyrotoxicosis also relapsed at this time. His condition fitted the diagnostic criteria of systemic lupus erythematosus. His antimicrosomal antibody titer was 1:1,600 (+) thyroid-stimulating hormone receptor antibody level was strongly positive, and the titer of antiinsulin antibody was high as well. These clinical, laboratory and histological findings indicate that class IV lupus nephritis may be associated with Graves' disease. PMID- 1606585 TI - Neonatal hyperparathyroidism. Conservative treatment with intravenous and oral rehydration solutions. AB - A neonate with primary hyperparathyroidism was successfully managed by conservative medical treatment. This treatment consisted of intravenous saline load, followed by oral rehydration solutions containing between 60-90 mmol/l of sodium. The combined administration of sodium and diuretics maintained normal levels of serum calcium. Similar cases were previously treated by parathyroidectomy with or without autotransplantation. In selected patients, medical treatment should be considered as the initial approach in mild neonatal hyperparathyroidism. It poses no specific risks and offers an alternative to surgical intervention. PMID- 1606586 TI - Persistent insulin-dependent diabetes mellitus in hemolytic uremic syndrome. AB - A 1.5-year-old Saudi girl with hemolytic uremic syndrome is described. She developed hyperglycemia in the acute stage which required insulin therapy. After a short remission, she developed permanent insulin-dependent diabetes mellitus. Review of the literature of the occurrence and the pathophysiology of this phenomenon is presented. PMID- 1606587 TI - Effect of hydrochlorothiazide on renal hypercalciuria. AB - The long-term effect of hydrochlorothiazide (HCT) was studied in 30 children (17 boys and 13 girls), aged 4-13 years (mean 7.6 +/- 3.4), with renal hypercalciuria (HCU) for a period of 2.5 +/- 0.95 years. The purpose of the study was to evaluate the effect of HCT mainly on renal calcium excretion, but also on serum K+, Ca, P, Mg, cPTH, nephrogenic cAMP (ncAMP) and bone mineral content (BMC). In addition to the above-mentioned parameters, oxalate, uric acid, citrate and cystine levels in 24-hour urine collections were also measured, and UCa/UCr, UP/UCr, UMg/UCr in 3-hour urine collections were assayed. The results of the study showed that 1 mg/kg/day of HCT caused a rapid and long-lasting correction of HCU, a decrease in serum cPTH and ncAMP, a significant increase in BMC and prevention of the formation of new urinary stones or of the increase in size of stones already present. No side effects were observed. PMID- 1606588 TI - Labial fusion and urinary tract infection. AB - We report 9 female patients with labial fusion and concomitant urinary tract infection. The mean age at presentation was 47 months. All except 1 patient had labial fusion extending at least 50% of the length of the labia minora. All had symptoms of urinary tract infection and a positive urine culture. We recommend that a urine culture be performed in children with labial fusion and that all girls with urinary tract infection should be checked for labial fusion. PMID- 1606589 TI - Pharmacological interventional testing for myocardial perfusion: a new application for adenosine. PMID- 1606591 TI - Plasmatic haemostasis in gonadotrophin-releasing hormone analogue therapy: effects of leuprorelin acetate depot on coagulatory and fibrinolytic activities. AB - The plasmatic parameters of coagulatory and fibrinolytic activity were studied in 15 patients with biopsy-proven endometriosis treated with leuprorelin acetate for 6 months. Bleeding time remained constant, indicating the absence of increased bleeding tendencies. The activity of the main inhibitor of the fibrinolytic response, plasminogen activator inhibitor, was reduced by 25%, suggesting an improvement in fibrinolytic reactivity. Plasma levels of fibrin degradation fragments were reduced by 35%, suggesting a marked reduction in the rate of fibrin generation and degradation. A simultaneous reduction in thrombin antithrombin III complexes and prothrombin fragment 1 + 2 (-10%) indicated that this effect was induced by reduced procoagulant activity, ie, thrombin generation. These data indicate that in gonadotrophin-releasing hormone (Gn-RH) analogue therapy the basal rate of coagulatory processes is reduced. The frequency and extent of fibrin-generating and degrading processes are reduced, suggesting a beneficial effect of Gn-RH analogues on the risk of thromboembolic disease. PMID- 1606590 TI - Influence on hormone levels, lipid metabolism and reversibility of endocrinological changes after leuprorelin acetate depot therapy. AB - The effect of leuprorelin acetate depot on the endocrine system and on lipid metabolism was evaluated in a multicentre, noncomparative study. During the first month of treatment, suppression of serum oestradiol levels to below 20 pg/ml was achieved and luteinising hormone and follicle-stimulating hormone levels were reduced to less than 50% of pretreatment values. A negative influence on lipid metabolism was not recorded. The high-density lipoprotein/low-density lipoprotein ratio did not change during therapy. Resumption of menstruation occurred within a mean period of 3 months after the last leuprorelin acetate depot injection. PMID- 1606592 TI - Formulation study of leuprorelin acetate to improve clinical performance. AB - Leuprorelin acetate, a highly potent gonadotrophin-releasing hormone agonist, was originally launched in the USA as a daily injection for the treatment of metastatic prostatic cancer. A once-monthly injectable depot form was subsequently developed. Biodegradable copoly(DL-lactic/glycolic) acid was chosen as the release-controlling polymer, and microspheres containing leuprorelin acetate were prepared by the in-water drying method. Results of studies in rats showed that a copolymer with a molecular weight of 14,000 and a lactic/glycolic acid ratio of 75/25 had the most satisfactory release-controlling properties. Microspheres given once monthly reduced serum testosterone levels in male rats. Microspheres also reduced serum oestradiol levels and caused a marked regression in experimental endometriosis in female rats. In clinical studies of prostatic cancer, use of the depot formulation has effectively reduced the dose required to as low as one-eighth of that needed for administration by daily injection. A sophisticated manufacturing system has now been developed and products now available have many advantages. PMID- 1606593 TI - Experience with leuprorelin acetate depot in the treatment of fibroids: a German multicentre study. AB - Between October 1988 and October 1990 in a noncomparative multicentre study, 114 patients were treated for uterine fibroids with the gonadotrophin-releasing hormone (Gn-RH) agonist, leuprorelin acetate depot. The mean age of the women was 33 years and 55.3% of them had a history of infertility. After confirmation of the diagnosis by ultrasound and/or operation, treatment began between day 1 and 3 of the cycle with leuprorelin acetate depot 3.75 mg subcutaneously. Therapy was carried out for a total of 6 months with one injection every 4 weeks. Treatment was paralleled by measurements of endocrine and metabolic parameters, estimation of myoma and uterine size by ultrasound and self-reporting of the patients of drug-related complaints. Four of the 114 women did not complete the whole treatment, two of them because of general side effects, one because of carcinophobia and unsatisfactory regression of the myoma and the last one for unspecified reasons. During treatment, a mean reduction of the uterine volume of about 67% was observed, in conjunction with shrinkage of the myoma in 92.1% of cases (mean decrease of 56% of the fibroids) with a large interindividual difference. Maximal diminution of uterine and fibroid size had been nearly completely reached within the first 12 weeks of therapy. After 4 weeks of the Gn RH agonist depot most of the patients had achieved postmenopausal status, which continued throughout the remaining 20 weeks of treatment. In accordance with this finding, the majority of general side effects was due to the hypo-oestrogenic endocrine status. Liver and lipid metabolism was almost unaffected, although increasing calcium and alkaline phosphatase serum levels as well as an increased urinary calcium/creatinine ratio demonstrated an increased metabolic turnover of the bone. Haemoglobin concentrations, however, increased in those cases with fibroid-related anaemia. Thus the slow-release form of leuprorelin acetate is an adjunct to myomectomy especially in those women in whom family planning is not yet completed. PMID- 1606594 TI - Efficacy of leuprorelin acetate depot in symptomatic fibromatous uteri: the Italian Multicentre Trial. AB - A total of 110 nonmenopausal women (mean age 42.1 years) presenting with symptomatic uterine leiomyomata and/or fibromatous uteri have been enrolled in this trial to evaluate the efficacy of the depot formulation of leuprorelin acetate in decreasing uterine volume and minimizing menorrhagia, dysmenorrhoea and pressure over the bladder. All patients were treated with an intramuscular injection of leuprorelin acetate depot 3.75 mg every 4 weeks for 16 weeks. Clinical examinations and hormonal and ultrasound determinations were performed before, during and at the end of treatment. Appropriate follow-up is still ongoing for most patients. At the end of the treatment period, of 88 women with enlarged fibromatous uteri, 33 (37.5%) showed a decrease in uterine volume of greater than or equal to 50% of the original size, while nine (10.2%) remained with unchanged uterine volume. Of 80 fibromas measurable separately, 47 (52.8%) decreased by greater than 50% of the initial volume and 16 (18%) remained unchanged or even increased. During treatment, clinically advantageous effects were observed in the associated symptomatology, mainly in the production of amenorrhoea and restoration of normal haemoglobin levels. Most of the patients were affected by irregular menstrual blood loss with consequent anaemia that in 29 patients was expressed by low levels of haemoglobin (mean 9.2 g/dl; SD 1.5; range 4.5-11.8 g/dl). By the end of the treatment, only one patient still had moderate vaginal blood loss. Haemoglobin levels rose to a mean value of 11.8 g/dl (SD 1.3; range 8.5-14.1 g/dl). Three patients (2.7%) failed to complete the 16 week treatment protocol, because of headache (one patient) and increased blood pressure (two patients). As a result of the treatment, of the 107 patients who were candidates for surgery and who were included in this study, only nine (8.4%) required surgery during leuprorelin acetate treatment. Of these, four operations were vaginal excision of the submucous myomata protruding into the cervix during treatment, and in five hysterectomy performed because of persistence of symptoms. In most patients the achievement of amenorrhoea minimized the fear of surgical emergency, facilitating an increased awareness of their clinical condition. With the exception of the three patients who dropped out, side effects were mild in all patients, consisting mainly of hot flushes, which were easily tolerated. In the following 8-12 months, the regrowth of uterine volume to original size has been usual in most of the 82 patients now in follow-up.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606595 TI - Use of gonadotrophin-releasing hormone agonists in controlled ovarian hyperstimulation for in vitro fertilization. AB - The aim of ovarian hyperstimulation for in vitro fertilization (IVF) is the recruitment of multiple fertilizable healthy oocytes. Transfer of multiple embryos yields a better success rate than single-embryo transfers. Moreover, cryopreservation of excess pre-embryos allows patients an added opportunity to achieve a pregnancy without undergoing a repeat stimulated cycle. In the last 4 years, gonadotrophin-releasing hormone (Gn-RH) agonists have been used widely as adjuncts to gonadotrophins for ovarian hyperstimulation. Advantages of Gn-RH agonist use include prevention of a premature luteinising hormone (LH) surge, suppression of endogenous basal LH levels and recruitment of a larger cohort of follicles. Gn-RH agonists can be used in a long (suppression) or a short (stimulatory, flare-up) protocol. In our clinic, the use of Gn-RH agonist suppression (starting in the mid-luteal phase) prior to ovarian hyperstimulation was demonstrated to be extremely beneficial in intermediate and high responder patients but not in low responders (defined endocrinologically as patients with a basal follicle-stimulating hormone [FSH]: LH ratio of 1:1 and a basal LH:FSH ratio of greater than or equal to 1.5, respectively). We have not been able to demonstrate any beneficial effects from the use of Gn-RH agonist suppression in low responder patients (defined endocrinologically as patients with a basal FSH greater than or equal to 15 mIU/ml). In such low responder patients, the use of a 'flare-up' Gn-RH agonist protocol (Gn-RH agonist starting on day 2 of the cycle, followed by gonadotrophins on day 4 of the cycle), taking advantage of the initial agonistic stimulatory effect of Gn-RH agonists on endogenous FSH and LH secretion, has provided significant improvements in stimulation characteristics and better pregnancy results. It should be emphasised that comparisons of results cannot be attempted due to the selective use of each protocol in different patient populations. PMID- 1606596 TI - Clinical and endocrine effects of leuprorelin acetate in pre- and postmenopausal patients with advanced breast cancer. AB - Premenopausal Study. Twenty-five pre- or perimenopausal patients with advanced breast cancer were treated with leuprorelin acetate 3.75 mg (n = 9) or 7.5 mg (n = 16) every 4 weeks. Serum levels of gonadotrophins and oestrogens were suppressed markedly by both doses and there was no indication that the lower dose was less effective as an oestrogen suppressant. There were four objective responders to the 3.75 mg dose and six to the 7.5 mg dose. Toxicity was confined almost entirely to hot flushes, which occurred in 17 patients. Leuprorelin acetate is therefore an effective agent in the treatment of premenopausal breast cancer patients. There appears to be no major detriment to the use of 3.75 mg rather than the 7.5 mg dose. Postmenopausal Study. Fifteen postmenopausal patients with advanced breast cancer were treated with monthly injections of leuprorelin acetate 7.5 mg to assess the clinical activity and endocrine responses to treatment. None of the 15 patients showed an objective response to treatment, although four patients had stable disease for at least 6 months. Endocrine effects after 4 weeks' treatment included major suppression of serum gonadotrophins to below 10% of pretreatment values and decreases in the level of serum testosterone in 12 of 14 patients. In this group there were no changes in oestradiol levels, although we had previously observed suppression in postmenopausal patients treated with goserelin. In common with other gonadotrophin-releasing hormone analogues, leuprorelin acetate cannot be recommended as a treatment for postmenopausal breast cancer. PMID- 1606597 TI - Coronary rotational ablation for unsuccessful angioplasty due to failure to cross the stenosis with a dilatation catheter. AB - Attempted coronary angioplasty of a right coronary artery sub-total occlusion was unsuccessful due to failure to cross the lesion with the dilatation catheter. Both fixed-wire and over-the-wire systems were tried. Coronary rotational ablation was successful in reducing the stenosis and allowing successful angioplasty. PMID- 1606598 TI - Accelerated coronary artery stenosis at a site proximal to coronary angioplasty. AB - Rapid progression of coronary stenosis has been described in patients undergoing percutaneous transluminal coronary angioplasty (PTCA), typically resulting in symptomatic angina 3 to 30 months postprocedure. We report a case of accelerated coronary stenosis in the instrumented vessel resulting in angina 3 days post PTCA. PMID- 1606599 TI - Extraction atherectomy during myocardial infarction in a patient with prior coronary artery bypass surgery. AB - In this case report of a patient presenting with an acute inferior wall myocardial infarction, the infarct conduit was a saphenous vein graft. Extraction atherectomy using the TEC successfully reestablished patency and reversed the patient's clinical symptoms. Extraction atherectomy is a feasible procedure during acute coronary events and deserves further investigation. PMID- 1606600 TI - Prolapsing large aneurysm of the atrial septum simulating a right atrial mass. AB - An unusual case of a large, prolapsing atrial septal aneurysm in a patient with an otherwise normal heart is described. The aneurysm caused right atrial obstruction and resulted in a "tumor effect." The patient experienced debilitating symptoms for years before receiving an appropriate diagnosis and curative surgical treatment. PMID- 1606601 TI - Right atrial myxoma associated with vascular malformation and atypical chest pain. AB - A 58-yr-old woman with a right atrial myxoma associated with a vascular malformation supplied by the right coronary artery is described. She presented with atypical chest pain that was reproduced during angiography of the malformation. Findings were confirmed during surgery. PMID- 1606602 TI - Mechanical right coronary artery shortening and vessel wall invagination: a fourth cause of iatrogenic coronary obstruction during coronary angioplasty. A case report and review of the literature. AB - Coronary spasm, dissection, and localized thrombosis are recognized sources of iatrogenic obstruction during coronary angioplasty. A fourth important cause is reported, namely, guidewire-induced mechanical straightening and shortening of tortuous right coronary artery resulting in the invagination of redundant vascular tissue. Reversal is achieved with guidewire retraction. Recognition of this entity is crucial to avoid unnecessary and potentially harmful intervention. PMID- 1606603 TI - Acquired postoperative coronary arteriovenous fistula. AB - A patient is described who underwent closed mitral valvotomy and presented 21 years later with left ventricular failure. Coronary angiography revealed a coronary artery to pulmonary vein arteriovenous fistula. This is the first report of an acquired fistula of this type developing secondary to trauma associated with cardiac surgery. Diagnosis and treatment implications are discussed. PMID- 1606604 TI - Instantaneous recruitment of reversed coronary collaterals that had been dormant for six years. AB - We report a case of instantaneous recruitment of reversed coronary collaterals 6 years after their disappearance with recanalization of the recipient vessel. Coronary collaterals can provide flow in both directions and remain immediately recruitable for years in case of occlusion of either vessel involved. PMID- 1606605 TI - Interpretation of cardiac pathophysiology from pressure waveform analysis: pericardial compressive hemodynamics, Part III. AB - Failure of right atrial pressure to normalize after pericardial pressure is relieved suggests persistent effusive-constrictive physiology, myocardial failure, or cardiomyopathy which may have indistinguishable hemodynamic pressure waveforms. Clinical characteristics, ancillary testing, and endomyocardial biopsy may be required to obtain a definite diagnosis in such cases. The hemodynamic waveforms obtained during pericardiocentesis provide insight into the pathophysiologic processes, producing symptoms of dyspnea in this interesting patient group. PMID- 1606606 TI - Definitive balloon catheter sizing in totally occluded coronary arteries. PMID- 1606607 TI - Concurrent triple valve percutaneous balloon valvuloplasty. PMID- 1606608 TI - Echocardiographic and angiographic evaluation of left ventricular function during percutaneous transluminal aortic valvuloplasty. AB - Transesophageal echocardiography was used to study the effect of the balloon inflation on left ventricular function in 20 patients with critical aortic stenosis undergoing balloon valvuloplasty. Balloon inflation caused an increase of end-diastolic (15% to 34%) and end-systolic (57% to 72%) left ventricular volume. Left ventricular wall stress increased from 30 +/- 10 x 10(3) dyn/cm2 at diastole and 121 +/- 40 x 10(3) dyn/cm2 at systole to 44 +/- 11 x 10(3) dyn/cm2 and 191 +/- 55 x 10(3) dyn/cm2, respectively, when the balloon was inflated (P less than 0.05). Turbulent regurgitant jet across the mitral valve increased from 15 +/- 2% to 25 +/- 3% during balloon inflation (P less than 0.01). Continued monitoring of left ventricular function after balloon deflation demonstrated prolonged enlargement of left ventricular volumes. Our data show that balloon inflation causes an increase of left ventricular volume and impairment of contraction. Increase of left ventricular wall stress--associated with a reduction of coronary blood flow, due to lower aortic pressure--could result in ischemic myocardial injury. PMID- 1606609 TI - Rotational ablation of coronary artery lesions using single, large burrs. AB - Previous clinical use of the Rotablator in coronary artery disease has involved a sequential increase in burr sizes up to 2 mm in diameter and has often utilized balloon adjunct to achieve an optimal result. We report our experience and describe our technique using a single, large burr (2.25, 2.5, or 2.75 mm diameter) without balloon assistance. The burr size was selected to approximate 70-90 percent of the apparent normal lumen diameter. Thirty-one patients with 36 lesions of complex morphology (eccentric, irregular, calcified, ulcerated, at bends, at bifurcations, completely occluded, as well as balloon failures) were successfully treated with the Rotablator. Results were assessed by computerized quantitative angiography. The percent diameter stenosis (mean +/- SD) for the group was reduced from 69.8 +/- 11.3% to 30.9 +/- 10% (p less than 0.001). The mean absolute diameter stenosis increased from 0.9 +/- 0.3 mm to 2.2 +/- 0.3 mm (p less than 0.001). Angiographically visible dissections were seen in 4 patients and were uncomplicated in 2. One patient had a non-Q-wave myocardial infarction. A fourth patient had a presumed acute occlusion 36 hr after the procedure, necessitating emergency bypass surgery, but without Q waves on the electrocardiogram or wall-motion abnormalities on the echocardiogram. Nitroglycerin was infused through the Rotablator catheter and has considerably lowered the degree and frequency of spasm. No other acute complications occurred. The mean procedure time using a single burr was shorter than when multiple burrs were used: 56.5 vs. 97.3 min, respectively (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606610 TI - High-speed rotational angioplasty-induced echo contrast in vivo and in vitro optical analysis. AB - High-speed rotational angioplasty is being evaluated as an alternative interventional device for the endovascular treatment of chronic coronary occlusions. It has been postulated that this type of angioplasty device may produce particulate debris or cavitations that induce myocardial ischemia. To determine the clinical presence of myocardial ischemia during rotational angioplasty, echocardiographic monitoring for wall motion abnormalities was performed in 9 patients undergoing rotational atheroablation using the Auth Rotablator for 10-sec intervals at 150,000 and 170,000 rpm. No wall motion abnormalities were detected in 5 patients evaluated with transesophageal echocardiography or in 4 patients monitored transthoracically, although AV block developed in one patient. Video intensitometry of the myocardial contrast effect for rotation times ranging from 3 to 20 sec found transient contrast enhancement of the myocardium supplied by the treated vessel. Intensity varied over time with half-time decay between 5.6 and 40 sec, indicating the likelihood of microcavitation. An in vitro model was constructed to measure the cavitation potential of the Auth Rotablator. A burr of 1.25 mm diameter rotating at 160,000 rpm achieves a velocity in excess of the 14.7 m/sec critical cavitation velocity. Testing the device in fresh human blood and distilled water produced microcavitations responsible for the enhanced echo effect, with the intensity and longevity of cavitation more pronounced in blood and proportional to the rotation time and speed. The mean size of the microcavitation bubbles in water was 90 +/- 33 (52-145) microns measured from photographs taken with a copper vapour laser emitting light pulses of 50 nsec duration as light source. The mean velocity of bubbles was found to be 0.62 +/- 0.30 ranging from 0.23 to 1.04 m/sec. It was measured via the motion of the bubbles during 5 laser pulses within 800 nsec. Clearly, microcavitations are associated with enhanced myocardial echo contrast effect. PMID- 1606611 TI - Transient translational silencing by reversible mRNA deadenylation. AB - Tissue-type plasminogen activator (tPA) mRNA is stored, stable and untranslated, in the cytoplasm of fully grown primary mouse oocytes. Dormancy is associated with an unusually short poly(A) tail, and poly(A) tail elongation controls tPA mRNA translational activation during meiotic maturation. Here we show that the nuclear transcript of this mRNA is extensively polyadenylated and that primary oocytes contain a deadenylating activity capable of silencing the cytoplasmic message. The sequence determinants that control deadenylation and polyadenylation overlap; this AU-rich region thus serves as an adenylation control element (ACE). The translation of a reporter mRNA in primary oocytes is prevented upon inclusion of an ACE in its 3' untranslated region. Therefore, the stage-specific regulation of poly(A) tail length accounts for the regulated synthesis of tPA in oocytes, and reversible deadenylation provides a mechanism for the translational control of dormant mRNAs. PMID- 1606612 TI - Expression cloning of a diphtheria toxin receptor: identity with a heparin binding EGF-like growth factor precursor. AB - A monkey cDNA (pDTS) encoding a diphtheria toxin (DT) sensitivity determinant was isolated by expression cloning in mouse L-M cells. Mouse cells are naturally resistant to DT, because they lack functional cell surface receptors for the toxin. Unlike wild-type L-M cells, pDTS-transfected mouse cells are extremely toxin sensitive and specifically bind radioiodinated DT. Intoxication of the transfected cells requires receptor-mediated endocytosis of the bound toxin. The cDNA is predicted to encode an integral membrane protein that is identical to the precursor of a heparin-binding EGF-like growth factor. The DT sensitivity protein is thus a growth factor precursor that DT exploits as a receptor. PMID- 1606613 TI - A maternal tail of poly(A): the long and the short of it. PMID- 1606614 TI - Purification, sequence, and cellular localization of a novel chromosomal protein that binds to methylated DNA. AB - Methylation of mammalian DNA can lead to repression of transcription and alteration of chromatin structure. Recent evidence suggests that both effects are the result of an interaction between the methylated sites and methyl-CpG-binding proteins (MeCPs). MeCP1 has previously been detected in crude nuclear extracts. Here we report the identification, purification, and cDNA cloning of a novel MeCP called MeCP2. Unlike MeCP1, the new protein is able to bind to DNA that contains a single methyl-CpG pair. By staining with an antibody, we show that the distribution of MeCP2 along the chromosomes parallels that of methyl-CpG. In mouse, for example, MeCP2 is concentrated in pericentromeric heterochromatin, which contains a large fraction (about 40%) of all genomic 5-methylcytosine. PMID- 1606615 TI - Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. AB - Gene targeting in embryonic stem (ES) cells has been used to mutate the murine DNA methyltransferase gene. ES cell lines homozygous for the mutation were generated by consecutive targeting of both wild-type alleles; the mutant cells were viable and showed no obvious abnormalities with respect to growth rate or morphology, and had only trace levels of DNA methyltransferase activity. A quantitative end-labeling assay showed that the level of m5C in the DNA of homozygous mutant cells was about one-third that of wild-type cells, and Southern blot analysis after cleavage of the DNA with a methylation-sensitive restriction endonuclease revealed substantial demethylation of endogenous retroviral DNA. The mutation was introduced into the germline of mice and found to cause a recessive lethal phenotype. Homozygous embryos were stunted, delayed in development, and did not survive past mid-gestation. The DNA of homozygous embryos showed a reduction of the level of m5C similar to that of homozygous ES cells. These results indicate that while a 3-fold reduction in levels of genomic m5C has no detectable effect on the viability or proliferation of ES cells in culture, a similar reduction of DNA methylation in embryos causes abnormal development and embryonic lethality. PMID- 1606616 TI - The two steps of nuclear import, targeting to the nuclear envelope and translocation through the nuclear pore, require different cytosolic factors. AB - We have isolated two cytosolic fractions from Xenopus oocytes that contain all of the activity necessary to support both steps of nuclear import in digitonin permeabilized mammalian cells: binding at the nuclear envelope and translocation through the nuclear pore. The first cytosolic fraction (fraction A) interacts with an import-competent, but not a mutant, nuclear localization sequence-bearing conjugate and stimulates its accumulation at the nuclear envelope in an ATP independent fashion. The second cytosolic fraction (fraction B) gives no discernible effect when added alone; but when added either together with fraction A, or after fraction A, stimulates the passage of the conjugate from the outer nuclear envelope to the interior of the nucleus in an ATP-dependent fashion. PMID- 1606617 TI - The argos gene encodes a diffusible factor that regulates cell fate decisions in the Drosophila eye. AB - The argos gene encodes a protein that is required for viability and that regulates the determination of cells in the Drosophila eye. A developmental analysis of argos mutant eyes indicates that the mystery cells, which are usually nonneuronal, are transformed into extra photoreceptors, and that supernumerary cone cells and pigment cells are also recruited. Clonal analysis indicates that argos acts nonautonomously and can diffuse over the range of several cell diameters. Conceptual translation of the argos gene suggests that it encodes a secreted protein. PMID- 1606618 TI - twine, a cdc25 homolog that functions in the male and female germline of Drosophila. AB - twine is the second homolog of the fission yeast gene cdc25 to be found in Drosophila. Both string and twine cDNAs can rescue a temperature-sensitive cdc25 mutation in fission yeast, but not a deletion. We detect the expression of string but not twine transcripts in the proliferating cells of newly cellularized embryos, in third instar larval brains, and in imaginal discs. Both genes are abundantly expressed in nurse cells during oogenesis, the maternal transcripts persisting throughout the syncytial stage of embryonic development. In the testis, twine transcripts are seen in the growing stage of premeiotic cysts. Analysis of a twine mutant suggests a requirement for the gene during oogenesis, during syncytial embryonic development, and for male meiosis. Meiosis does not occur in homozygous twine males, which produce cysts containing 16 rather than 64 spermatids. PMID- 1606619 TI - A naturally occurring peptide recognized by alloreactive CD8+ cytotoxic T lymphocytes in association with a class I MHC protein. AB - The antigenic structures that initiate T cell responses to foreign (allogeneic) cells have long attracted considerable interest. We have purified and sequenced a peptide from mouse spleen that is recognized in association with the class I MHC protein H-2Ld by 2C, an alloreactive CD8+ T cell clone. The peptide (LSP-FPFDL) greatly enhances the susceptibility of Ld+ cells to lysis by 2C, and this activity is completely blocked by a clonotypic antibody against the 2C T cell receptor. Thus, this study characterizes the naturally occurring peptide moiety of an MHC-I/peptide complex recognized by alloreactive CD8+ T cells. The peptide, which occurs in the thymus of MHC-disparate mice, can be used to study T cell development in mice expressing transgenes for the 2C T cell receptor. PMID- 1606620 TI - Distribution of DNA polymerase alpha during nuclear division cycles in Drosophila melanogaster embryo. AB - An immunocytochemical method using a specific monoclonal antibody was employed to detect DNA polymerase alpha in Drosophila melanogaster embryos during the first 13 nuclear division cycles after fertilization. The anti-DNA polymerase alpha antibody stained the ooplasm of the unfertilized egg, indicating that DNA polymerase alpha is maternally stored. Strong nuclear staining with the antibody over the weaker staining of the cytoplasm was observed at interphase throughout the 13 nuclear division cycles. The staining of the cytoplasmic regions surrounding the nucleus was much stronger than the other region of the syncytial cytoplasm until cycle 10. Although prophase nuclei were stained with the antibody, metaphase chromosomes were never stained throughout the 13 cycles. The chromosomal (nuclear) staining reappeared at anaphase until cycle 11 and at telophase in later cycles. The staining of the syncytial cytoplasm except for the cortical region became faint by cycle 13, suggesting the consumption of the maternal storage by this cycle. These results suggest that DNA polymerase alpha dissociates from chromosomes at the beginning of metaphase; then in later mitotic phases, it is transported from the syncytial cytoplasm into nuclei to participate in formation of the active DNA replication enzyme complex. PMID- 1606621 TI - Complementation by a cloned human ubiquitin-activating enzyme E1 of the S-phase arrested mouse FM3A cell mutant with thermolabile E1. AB - A temperature-sensitive growth mutant tsFS20 isolated from mouse FM3A cells was identified as a mutant with thermolabile ubiquitin-activating enzyme E1 by transfection with a full-length cDNA encoding the human E1 enzyme and cell-cell hybridization with an authentic E1 mutant ts85 previously isolated from FM3A cells. The resulting transformants produced thermoresistant E1 activity. Upon shift-up of temperature, asynchronously growing tsFS20 cells showed multiple points of cell-cycle arrest. At the nonpermissive temperature, tsFS20 cells that had been synchronized at the G1-S-phase progressed and accumulated in the mid-S phase, as evidenced by the absence of G2-specific cdc2 kinase activity, while ts85 mutant cells, the widely used E1 mutant, reached the G2-phase and were arrested. Thus, the E1 mutation seemed to be involved in progression in the S phase as well as in the G2-phase in the cell cycle. Degradation of short-lived abnormal proteins in tsFS20 cells was decreased to about 50% at the nonpermissive temperature, while the block was fully restored to the wild-type level in the transformant cells. Relevance of the unusually high incidence of the temperature sensitive E1 mutation was discussed in terms of the E1 as a determinant of heat tolerance of cells. PMID- 1606622 TI - Nuclear migration and spindle formation in the fourth cleavage of sea urchin eggs under the influence of inhibitors. AB - Mitosis of sea urchin eggs was inhibited when exposed to 3 micrograms/ml aphidicolin from the 2-cell stage onwards. Nevertheless the nuclei migrated to the vegetal pole at the time of the fourth unequal division in control eggs. Two or four equal or unequal asters developed. Asters in proximity to the vegetal pole were always considerably smaller than those close to the center of the two blastomeres. In contrast to colchicine, cytokinesis but not migration of the nuclei in the vegetal half was prevented by treatments with 5 microM cytochalasin B or D. Various mitotic figures were formed in the vegetal blastomeres of eggs treated with 0.4 mM colchicine or 3 microM griseofulvin after the third cleavage. In some eggs a centrally localized monaster with chromosomes in sphere-like arrangement was formed in others a monopolar mitotic figure pushed the chromosomes in bowl-like arrangements to the most vegetal cortex. In anaphase one set of chromatids migrated to the monopole leaving the scattered sister chromatids behind. The mechanism of migration of the nuclei and of chromosome arrangement in the metaphase plate is discussed. PMID- 1606623 TI - Identification of fibronectin in chicken thrombocytes. AB - Cell attachment and spreading of chicken embryo fibroblasts and three mammalian cell lines were promoted by using thrombocyte secretion products (TSP) prepared from chicken thrombocytes which are analogous to mammalian platelets. The cell attachment activity following TSP treatment was interfered with by the addition of a synthetic peptide containing the RGD sequence from the cell attachment region of fibronectin (FN). Cell attachment on TSP-coated plates was inhibited by the addition of anti-chicken FN rabbit antiserum, but not by anti-chicken vitronectin (VN) rabbit antiserum. By immunoblotting, immunofluorescent test and sensitive enzyme linked immunosorbent assay using an anti-chicken FN antiserum, the presence of FN in thrombocytes and the release of FN from the cells were demonstrated. The release of FN from thrombocytes was partially induced by the in vitro cultivation of the cells and was further promoted by treatment of the cells with thrombin. PMID- 1606624 TI - Long-term maintenance of multilineal hemopoiesis in collagen gel culture. AB - We examined the long-term maintenance of multilineal hemopoiesis in a collagen gel culture of mouse bone marrow cells. When cells were inoculated into the gel, stromal cells formed foci that were composed of sinusoidlike capillary structures, fibroblastic cells, adipocytes and macrophages. Many small hemopoietic foci similar to granulocyte-macrophage colonies (CFU-GM) appeared within a week and disappeared after two weeks. Several large hemopoietic foci appeared after two to three weeks of culture, without a second challenge of marrow cells. These large hemopoietic foci were composed mainly of myeloid cells. Megakaryocytes and mast cells were also observed. When erythropoietin (EPO) was added to the culture at the beginning, the erythroid focus appeared after 3 weeks and the number of megakaryocytes was greater than that in the culture without EPO. However, when EPO was added to the cultures after 6 or 12 weeks, erythroid cells appeared after 1 week and the number of megakaryocytes increased. This hemopoiesis lasted more than 6 months. PMID- 1606625 TI - Changes in the cytoskeleton pattern of tumor cells by cisplatin in vitro. AB - The influence of the antitumor drug cis-diamminedichloroplatinum(II) ('cisplatin') upon the structural pattern of the main cytoskeletal components, i.e. microtubules, intermediate filaments and microfilaments, was investigated in squamous carcinoma cells derived from the mouse stomach (G 22) or the human lung (L 266) and growing in vitro as monolayer cultures. The studies were performed by the indirect immunofluorescence technique using monoclonal antibodies against alpha-tubulin, type 19 cytokeratin and actin at the end of a 90-min exposure to 2.5 x 10(-6), 5 x 10(-6) or 10(-5) mol cisplatin/l and a subsequent 24-h recovery period. Under the influence of cisplatin, the cytoskeletal tubules and filaments, which were distributed in untreated cells as a finely organized network spreading through the whole cytoplasm like a spider's web, collapsed and aggregated to dense and circularly arranged bands of bright immunofluorescence around the nucleus or to cap-like structures apposing the nucleus. These phenomena developed in clear dependence upon the dose of cisplatin applied and were observable in a modified manner and to a different degree with the three structural elements of the cytoskeleton. During the subsequent 24-h interval, during which the cells were allowed to recover in drug-free growth medium, the before-mentioned collapse of the cytoskeletal network was only partially reversible following previous treatment with the medium (5 x 10(-6) mol/l) and the high (10(-5) mol/l) dose of cisplatin and restored totally to the normal structural pattern of untreated control cells when the low dose of 2.5 x 10(-6) mol cisplatin/l had been administered before. These results give evidence that the DNA cannot be the only cellular target for the antitumor drug cisplatin, but that it also effects other intracellular lesions which cause structural alterations of cellular organelles independently of the primary molecular attack at nuclear DNA strands. Probably, these additional interactions fortify the antiproliferative effect and contribute to the achievement of important biological and cytological effects of cisplatin such as growth inhibition or giant cell formation. PMID- 1606626 TI - Covalent binding of perfluorinated fatty acids to proteins in the plasma, liver and testes of rats. AB - Perfluorinated fatty acids alter hepatic lipid metabolism and are potent peroxisome proliferators in rodents. Two such perfluorinated acids, perfluorodecanoic acid (PFDA) and perfluorooctanoic acid (PFOA), were examined to determine if they covalently bind cellular proteins. PFDA and PFOA were found to covalently bind proteins when administered to rats in vivo. The liver, plasma and testes of male rats treated with [1-14C]PFDA or PFOA (9.4 mumol/kg) contained detectable levels of covalently bound 14C (0.1-0.5% of the tissue 14C content). Characterization of PFDA covalent binding to albumin in vitro showed that cysteine significantly decreased binding with no effect of methionine, suggesting protein sulfhydryl groups are involved. In cytosolic and microsomal incubation there was no effect of the addition of CoA, ATP or NADPH on the magnitude of the covalent binding of PFDA. Therefore PFDA need not be metabolically activated to form covalent adducts. Despite demonstration of covalent binding of PFDA and PFOA to proteins both in vivo and in vitro, the role of this macromolecular binding in perfluorinated fatty acid toxicity is not known. PMID- 1606627 TI - Influence of methoxy and nitro groups in the oxidative metabolism of naphtho[2,1 b]furan. AB - In the present study, we have investigated the role of methoxy and nitro groups in the oxidative metabolism of naphtho[2,1-b]furan. Hepatic microsomes were used to investigate the aerobic metabolism of naphtho[2,1-b]furan (compound A), 2 nitro-naphtho[2,1-b]furan (compound B) and 7-methoxy-naphtho [2,1-b]furan (compound C) and comparison of the metabolites formed was made using HPCL analysis and NMR, mass and UV-visible spectrometry. The different metabolic pathways investigated were compared with the previously reported metabolism of 7 methoxy-2-nitro-naphtho[2,1-b]furan (compound D). Naphtho[2,1-b]furan yield metabolites of both the furan and benzene rings, while metabolites formed from 7 methoxy-naphtho[2,1-b]furan and 2-nitro-naphtho [2,1-b]furan were derived entirely as a result of enzymic attack on the first benzene ring. PMID- 1606628 TI - Molecular design of potent inhibitor specific for cathepsin B based on the tertiary structure prediction. AB - To design a potent inhibitor specific for cathepsin B (rat liver), the tertiary structure was predicted based on the crystal structure of the papain complexed with (+)-(2S,3S)-3-(1-[N-(3-methylbutyl)amino]leucylcarbonyl)oxirane-2- carbolylic acid (E-64-c), a thiol protease inhibitor. Taking advantage of the structural characteristics of the predicted active site, seventeen inhibitors were chemically synthesized by molecular modeling, and one of them, N-(L-3-trans propylcarbamoyloxirane-2-carbonyl)-L-isoleucyl-L-p rol ine (CA-074) was shown to be the first potent inhibitor specific for cathepsin B. The relationship between the structure and inhibitory activity is discussed based on the model structure of the cathepsin B-inhibitor complex. PMID- 1606629 TI - Studies on the enzyme immunoassay of bio-active constituents in oriental medicinal drugs. VI. Enzyme immunoassay of ginsenoside Rb1 from Panax ginseng. AB - Enzyme immunoassay (EIA) of ginsenoside Rb1 (GRb1), one of the glucosides of protopanaxadiol from Panax ginseng, was explored. A carrier protein (bovine serum albumin (BSA)) was coupled to the C-26 position on the unsaturated side chain of the protopanaxadiol moiety to prepare the immunogen. In order to perform bridge heterologous EIA, a label (beta-D-galactosidase) was introduced at C-26 of the saturated side chain to obtain labeled antigen. Anti-GRb1 antisera were elicited in rabbits by immunization with GRb1-BSA conjugate (9). The double antibody method (with goat anti-rabbit IgG antiserum) was used to separate the bound and free GRb1-beta-Gal. A satisfactory standard curve for EIA of GRb1 was obtained in the range of 0.04-10 ng/tube. In a comparison of the assay results obtained by EIA and HPLC, the linear regression equation and correlation coefficient for the two methods were y (EIA) = 9.18x(HPLC)-0.033 and 0.98, respectively. The anti GRb1 antiserum cross-reacted with GRb2 (21.8%) and GRc (10.6%), which are also constituents of Panax ginseng. PMID- 1606630 TI - Purines. L. Synthesis and antileukemic activity of the antibiotic guanine 7-oxide and its 9-substituted derivatives. AB - A full account is given of the first chemical synthesis of the antitumor antibiotic guanine 7-oxide (5) and its 9-substituted derivatives (24a--k and 26). Coupling of appropriate primary amines (17a--e, g--k) with phenacyl bromide (16) produced, after treatment with HCl, the corresponding N-substituted phenacylamine hydrochlorides (18a--e, g--k). A similar phenacylation of 4-amino-l-butanol (21) failed to give the desired compound 18f, so that 21 was heated with 2-bromomethyl 2-phenyl-1,3-dioxolane (20) at 150-155 degrees C for 3h to furnish, after treatment with HCl, the amino ketal hydrochloride 22 in 40% yield. Deketalization of 22 with hot 2 N aqueous HCl afforded 18f in 96% yield. Condensations of the free bases, generated in situ from the hydrochlorides 18a--l and 1N aqueous NaOH, with the chloropyrimidinone 6 were effected in aqueous EtOH at the boiling point for 20 min or at 25-30 degrees C for 3-24h, giving the 6-phenacylamino-4 pyrimidinones 19a-l in 54-90% yields. On treatment with 2N aqueous NaOH at room temperature for 10-60 min, the nitropyrimidinones 19a--k cyclized to provide the 9-substituted guanine 7-oxides 24a--k in 61-98% yields. A similar alkali treatment of 191 failed to yield guanine 7-oxide (5). However, removal of the 9 (arylmethyl) group from 24i--k was effected with conc. H2SO4 at room temperature for 1-3h in the presence of toluene, producing the target N-oxide 5 in 56-89% yields.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606632 TI - Renin inhibitors. I. Synthesis and structure-activity relationships of transition state inhibitors containing homostatine analogues at the scissile bond. AB - The synthesis and structure-activity relationships of transition-state renin inhibitors containing the homostatine analogues at the scissile bond are described. These inhibitors incorporate the amino acid side chains corresponding to positions 7-12 (P4-P2') of angiotensinogen. Ethyl, 2-hydroxyethyl and 3 hydroxypropyl groups at position 2 of the homostatine analogues (P1') are more effective for increasing potency than the isopropyl group. A combination of residues at P1, P3 and P4 is important for potency and this result suggests that S1, S3 and S4 form a huge hydrophobic core together in renin. PMID- 1606631 TI - Synthesis and antiallergy activity of [1,3,4]thiadiazolo[3,2-a]-1,2,3 triazolo[4,5-d]pyrimidin-9 (3H)-one derivatives. I. AB - A series of 6-substituted [1,3,4]thiadiazolo[3,2-a]-1,2,3-triazolo[4,5 d]pyrimidin-9(3H)-one derivatives 4a--z were synthesized from 5-substituted 1,3,4 thiadiazol-2-amines 5 by the following consecutive reactions: pyrimidine ring closure with bis(2,4,6-trichlorophenyl) malonate, nitration, chlorination, amination, hydrogenation and diazotization. The structure of 4 was confirmed by an alternate synthesis of 4, involving reaction of 5-substituted 2-azido-1,3,4 thiadiazole 13 with ethyl cyanoacetate, followed by the Dimroth rearrangement and ring closure. The antiallergic activities (anti-passive peritoneal anaphylaxis, anti-passive cutaneous anaphylaxis and anti-slow reacting substance of anaphylaxis activities) of the products were evaluated. PMID- 1606633 TI - Studies on antiulcer drugs. II. Synthesis and antiulcer activities of imidazo[1,2 alpha]pyridinyl-2-alkylaminobenzoxazoles and 5,6,7,8-tetrahydroimidazo[1,2 alpha]pyridinyl derivatives. AB - A series of imidazo[1,2-alpha]pyridinylbenzoxazoles (4) and 5,6,7,8 tetrahydroimidazo[1,2-alpha]pyridinylbenzoxazoles (5) were synthesized and tested for anti-stress ulcer activity in rats. Several compounds were found to be more active than the reference compounds, sucralfate, cimetidine and ranitidine. Some of them exhibited potent protective activity against ethanol-induced gastric lesion. The synthesis and structure-activity relationships of these compounds are discussed. PMID- 1606634 TI - Inhibition of prostaglandin and leukotriene biosynthesis by gingerols and diarylheptanoids. AB - The rhizomes of Zingiber officinale (ginger) and Alpinia officinarum contain potent inhibitors against prostaglandin biosynthesizing enzyme (PG synthetase). Gingerols and diarylhepatanoids were identified as active compounds. Their possible mechanism of action which was deduced from the structures of active compounds indicated that the inhibitors would also be active against arachidonate 5-lipoxygenase, an enzyme of leukotriene (LT) biosynthesis. This was verified by testing their inhibitory effects on 5-lipoxygenase prepared from RBL-1 cells. A diarylheptanoid with catechol group was the most active compound against 5 lipoxygenase, while yakuchinone A was the most active against PG synthetase. PMID- 1606635 TI - Inhibition of in vitro prostaglandin and leukotriene biosyntheses by cinnamoyl beta-phenethylamine and N-acyldopamine derivatives. AB - N-trans- and N-cis-Feruloyltyramines were isolated as the inhibitors of in vitro prostaglandin (PG) synthesis from an Indonesian medicinal plant, Ipomoea aquatica (Convolvulaceae). In order to clarify structure activity relationships, cinnamoyl beta-phenethylamines with possible combinations of naturally occurring cinnamic acids and beta-phenethylamines were synthesized and tested for their inhibitory activities against PG synthetase and arachidonate 5-lipoxygenase. The compounds containing catechol groups such as N-caffeoyl-beta-phenethylamine (CaP) showed higher inhibitory effects on PG synthetase. The catechol group was found to be essential for the inhibition of arachidonate 5-lipoxygenase. The investigation of concentration dependent effects on PG biosynthesis revealed that CaP enhanced PG biosynthesis at a lower concentration range, whereas it inhibited the reaction at a higher concentration. The effects of CaP on each reaction step were investigated with purified PG endoperoxide synthase and microsomal PG synthetase. CaP inhibited the cyclooxygenase reaction, while it enhanced the hydroperoxidase reaction. N-Acyldopamines which contain catechol and lipophylic group were synthesized from dopamine and fatty acids to test their inhibitory effects on arachidonate 5-lipoxygenase. N-Linoleoyldopamine was the most active compound and its IC50 value was 2.3 nM in our assay system, in which an IC50 value of AA 861, a specific inhibitor of 5-lipoxygenase, was 8 nM. PMID- 1606636 TI - Studies on differentiation-inducing activities of triterpenes. AB - Differentiation-inducing activity of over 180 extracts of crude drugs and plants was tested using mouse myeloid leukemia cell line (M1). The methanol extracts of clove (Syzygium aromaticum Merrill et Perry, Myrtaceae) showed remarkable induction of differentiation of M1 cells into macrophage-like cells. From the extract, oleanolic acid (1) and crategolic acid (2) were isolated as the active components. We also tested other triterpenes, such as oleananes, ursanes and dammaranes, to investigate the structure-activity relationship. Some triterpene aglycones showed differentiation-inducing activity, but triterpene glycosides showed little activity. Furthermore, the differentiation-inducing activity of these triterpene compounds was tested against human acute promyelocytic leukemia cell line (HL-60). PMID- 1606637 TI - Anti-lipid peroxidative effect of an extract of the stems of Kadsura heteroclita and its major constituent, kadsurin, in mice. AB - Three-days successive p.o. administration of an EtOH extract of the stems of Kadsura heteroclita (Schizandraceae) or its major constituent, kadsurin, resulted in significant decreases of CCl4-induced lipid-peroxidation products, such as thiobarbituric acid reactive substances (TBA-RS), conjugated dienes and fluorescent products in the liver of mice. In contrast, a significant restoration of superoxide dismutase (SOD) activity reduced by CCl4-intoxication was observed in the administered groups, suggesting that the subchronic treatment of mice with the EtOH extract or kadsurin induce enzymes capable of scavenging oxygen radical species in the liver, though the extract and kadsurin themselves may have an anti oxidant property. PMID- 1606638 TI - Radioimmunoassay for the determination of 2-methoxyestriol concentration in plasma of pregnant women. AB - A specific assay method has been developed for the determination of 2 methoxyestriol in plasma of pregnant women. The quantitation was achieved by radioimmunoassay after extraction of the plasma with ethyl acetate and purification on a Sephadex LH-20 column. In order to obtain the immunogen for 2 methoxyestriol, 6-oxo-2-methoxyestriol was converted to its 6-(O carboxymethyl)oxime derivative. The derivative was then coupled to bovine serum albumin by the mixed anhydride method, and rabbits were immunized with this conjugate. The antiserum obtained was partially purified by affinity chromatography on estrone 17-(O-carboxymethyl)oxime-aminohexyl Sepharose conjugate to eliminate the cross-reactive antibodies. Plasma 2-methoxyestriol concentrations in pregnancy were estimated to be mean values of 41.1 pg/ml (12th 14th week), 85.3 pg/ml (27th-29th week), and 97.5 pg/ml (37th-41st week). PMID- 1606639 TI - Effect of nitrite on cell growth and antibody production in mouse splenic B cells stimulated with lipopolysaccharide and B cell hybridomas. AB - Nitric oxide, nitrite and nitrate are released by activated macrophages in an immune response. We showed here that nitrite influenced cell growth and antibody production in mouse lipopolysaccharide (LPS)-stimulated splenic B cells and B cell hybridomas. The addition of 10(-7) and 10(-6) M nitrite enhanced deoxyribonucleic acid (DNA) synthesis of LPS-stimulated splenic B cells. However, DNA synthesis and antibody production in the case of total spleen cells stimulated with LPS were suppressed by nitrite in a dose dependent-manner. These phenomena were also observed in a similar experiment involving mouse B cell hybridomas. Antibody production of all B cell hybridomas was significantly suppressed by the addition of nitrite. This suppressing effect could not be explained by changes in viable cell yields. This data suggests that the antibody production and cell proliferation of B cells may be influenced by nitrite from activated macrophages in the immune response. PMID- 1606640 TI - Enzymatic generation of alloxan radicals in rat liver microsomes: possible participation of reduced nicotinamide adenine dinucleotide phosphate (NADPH) cytochrome P-450 reductase. AB - Electron spin resonance studies showed that addition of rat liver microsomes to the reaction system of alloxan with reduced nicotinamide adenine dinucleotide phosphate (NADPH) resulted in a marked increase in the generation of alloxan radicals (AH.), whereas heat-denatured microsomes were without such effect. Oxidation of NADPH by alloxan was also stimulated by microsomes. The microsomes from rats treated with phenobarbital, an inducer of cytochrome P-450 reductase, greatly stimulated both the AH.generation and the NADPH oxidation. However, the microsomes from rats treated with 3-methylcholanthrene, an inducer of DT diaphorase, did not have stimulative effect greater than the control microsomes. These results suggest the possibility that NADPH-linked AH.generations in microsomal membranes is catalyzed by NADPH-cytochrome P-450 reductase. PMID- 1606641 TI - Effect of an inhibitor of squalene epoxidase, NB-598, on lipid metabolism in Hep G2 cells. AB - NB-598, a potent inhibitor of squalene epoxidase, inhibited cholesterol synthesis from [14C]acetate and induced intracellular squalene accumulation in Hep G2 cells. NB-598 inhibited cholesterol synthesis from [14C]acetate, [3H]mevalonate, and [3H]squalene, but not from [3H]2,3-oxidosqualene in Hep G2 cells. It reduced cholesterol ester synthesis remarkably in the absence of exogenous cholesterol. This compound did not have any effect on the synthesis of ubiquinone and dolichol. When Hep G2 cells were prelabeled with micellar [3H]cholesterol, NB-598 did not affect the excretion of bile acid incorporated from [3H]cholesterol. However, NB-598 decreased the secretion of free and esterified cholesterol, triacylglycerol, and phospholipids, and increased the secretion of squalene. NB 598 is thought not only to inhibit cholesterol synthesis, but also to inhibit the secretion of lipids. PMID- 1606642 TI - Interaction of toxic lectin ricin with epithelial cells of rat small intestine in vitro. AB - To clarify the mechanism of oral toxicity of ricin, the interaction of ricin with the epithelial cells isolated from rat small intestine was compared in vitro with those of other plant lectins by two different determinations, i.e., viability and cytotoxicity. After incubation of the cells for 1 h at 37 degrees C with ricin, B chain, castor bean hemagglutinin (CBH), soybean agglutinin (SBA), wheat germ agglutinin (WGA), concanavalin A (Con A), and peanut agglutinin (PNA), respectively, followed by staining with trypan blue, ricin and ricin B-chain as well as CBH and SBA were found to have effectively reduced the number of viable cells. On the contrary, only ricin inhibited protein synthesis in the cells and the effect was blocked by D-galactose. Additional experiments employing [125I] labeled ricin strongly suggested that ricin was first bound via its B-chain to the galactosyl residues on the cell surface followed by internalization into cells as the whole 62 kDa molecule. These results infer first that ricin, as well as other lectins mentioned above, was able to reduce viability of the epithelial cells of rat small intestine by direct binding to the cell surface. The second effect, specific to ricin, was the inhibition of cellular protein synthesis. PMID- 1606643 TI - Abrogation of the suppressive effect of 12-O-tetradecanoylphorbol 13-acetate and 7,12-dimethylbenz[a]anthracene on footpad reaction of mice by indomethacin and some inhibitors of tumor promotion. AB - Influences of indomethacin, which has been known as an inhibitor of the production of prostaglandins, on the suppression of footpad reaction (FPR) of BALB/c mice against sheep red blood cells by the painting of 12-O tetradecanoylphorbol 13-acetate (TPA, a typical tumor promoter) were studied. The temporary suppressive effect by the painting of TPA (8 nmol) was abrogated by the painting of indomethacin (7-70 nmol) 60 min before TPA treatments. The lasting suppressive effect by TPA treatment (8 nmol/d) for 7 d following the painting of 7,12-dimethylbenz[a]anthracene (DMBA, 400 nmol), which is a typical tumor initiator, also disappeared when indomethacin (7 nmol) was painted 30-90 min before each TPA treatment. Influences of some inhibitors of tumor promotion on the lasting suppressive effect of FPR by DMBA and TPA were also tested. Painting of 0.6 mumol of 1-phenyl-2-pyrazolidone, 8.2 nmol of salcophytol A, 17 nmol of retinoic acid, 5.6 mumol of 3(2)-tert-butyl-4-hydroxyanisol, and 3 mumol of quercetin 45 min before each TPA treatment decreased the suppressive effect on the footpad reaction. PMID- 1606644 TI - Relationship between the transference of a drug from a transdermal patch and the physicochemical properties. AB - The transferred percentages of 13 drugs to rat skin from transdermal patches were studied to reveal the relationship to their physicochemical properties. The drugs to be tested had melting points of 13.5-234 degrees C, lipophilic indices of 0.475-5.336, and molecular weights of 122.12-392.45. The transferred percentage of drug to intact skin was lower, the higher the melting point, lipophilic index and molecular weight. The same was true in stripped skin, where the transferred percentage of drug was markedly increased. The difference between transferred drug percentages to stripped and intact skin, which could be regarded as the regulatory contribution of the stratum corneum, tended to be larger, the lower the drug's melting point and lipophilic index. PMID- 1606645 TI - Factors affecting prednisolone release from hydrogels prepared with water-soluble dietary fibers, xanthan and locust bean gums. AB - The release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums was investigated. Newly developed equipment was employed in order to increase the gum concentration in the hydrogels. The apparent release rate of prednisolone from the hydrogels decreased with increasing gum concentration, suggesting that the diffusion of drug molecules was mainly controlled by the density of the three-dimensional network structure in the matrix. The effect of additives such as glycerin and sucrose on the release behavior of prednisolone was also investigated in detail. Drug release was significantly lowered by the addition of these compounds to these hydrogels. A linear relation was observed between the apparent release rate of prednisolone and microscopic viscosity of the hydrogels. These results indicated that the drug release could be controlled not only by the density of the network structure but also by the microscopic viscosity of the hydrogels. PMID- 1606646 TI - Utility of mixture of commercially available polymers as constituents of sustained-release microcapsules containing cefadroxil or theophylline. AB - Hydroxy propyl methyl cellulose acetate succinate high grade (AS-HG) and ethyl cellulose (EC) mixture microcapsules containing cefadroxil or theophylline were prepared by a solvent evaporation method in liquid paraffin dissolved sorbitan tri-stearate as a dispersing agent, and their sustained-release properties were evaluated. The microcapsules prepared with AS-HG:EC (in a 2:5 weight ratio) mixture containing 20% of cefadroxil or theophylline exhibited apparent zero order releasing pattern in pH 6 to 8, at 50 rpm and 37 degrees C (paddle method). These microcapsules were administered orally to beagle dogs and the plasma concentrations of cefadroxil or theophylline were measured periodically. As a result of in vivo investigation, a satisfactory sustained-release plasma pattern and an apparent zero-order process in the gastrointestinal absorption were confirmed by deconvolution analysis of both drugs. PMID- 1606647 TI - Homeostasis as regulated by activated macrophage. I. Lipopolysaccharide (LPS) from wheat flour: isolation, purification and some biological activities. AB - Based on our new concept of ontogenic inflammation, we have sought a substance which can prime macrophage in terms of the endogenous production of tumor necrosis factor (TNF). A lipopolysaccharide (LPSw) was found in wheat flour, purified and characterized. The molecular size of LPSw was about 5 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and it contained 3-deoxy-D manno-octulosonic acid: 1, hexosamine: 4 and one phosphorus in a single molecule. LPSw can prime macrophage to release TNF when given intradermally, percutaneously or even orally in mice as well as in humans, in exactly the same way as intravenous administration of interferon gamma. PMID- 1606649 TI - Studies on chemical protectors against radiation. XXXV. Effects of radioprotective Chinese traditional medicines on radiation-induced lipid peroxidation in vivo and in vitro. AB - The fluctuation of lipid peroxidation (LP) in 9 tissues was investigated in mice for 7 d after whole-body X-irradiation with a lethal dose of bone marrow death. LP increased significantly in bone marrow, thymus, spleen and liver following irradiation, and slightly in brain and testis, but not in blood plasma, submaxillary gland or kidney. The effects of 7 radioprotective Chinese traditional medicines (CTMs) and cysteamine (MEA) on the radiation-induced LP in 4 tissues were studied by i.p. injection before or after irradiation and their LP content in tissues was measured 2 d after irradiation. Most CTMs showed significant inhibition of radiation-induced LP in bone marrow and liver, especially when injected prior to irradiation. Some CTMs also showed such inhibition in spleen. MEA only inhibited the increase of LP in liver when injected before irradiation, but enhanced the increase of LP in spleen. None of these radioprotectors including MEA was recognized to inhibit radiation-induced LP in thymus. The in vitro experiments were carried out using mouse liver microsomal suspensions (MS). The MS were prepared from normal (non-irradiated) mice. Each of the 8 radioprotectors was added to MS before or after irradiation and then post-irradiation-incubated at 37 degrees C. All markedly inhibited radiation-induced LP if added before irradiation, but were slightly less effective if added after. PMID- 1606648 TI - Destabilization of whole skin lipid bio-liposomes induced by skin penetration enhancers and FT-IR/ATR (Fourier transform infrared/attenuated total reflection) analysis of stratum corneum lipids. AB - Whole skin lipid bio-liposomes (skin bio-liposomes), in size ranging from 2 to 8 microns, were prepared by a reverse phase evaporation technique using rat full thickness skin. Leakage of an encapsulated fluorescence probe, ANTS (delta-amino 1,3,6-naphthalene-trisulfonate), was measured by adding transdermal penetration enhancers (penetrants) into the medium where the skin bio-liposomes were present. Oleylamine induced a fast release of ANTS from the liposomes compared to lauryl amine which showed a weak action. With these penetrants, the degree of ANTS release from the prepared bio-liposomes was found to correlate well with the results of frequency changes in the CH-asymmetric stretching band near 2920 cm-1 in the rat stratum corneum. The penetrant which caused relatively strong leakage of ANTS induced the significantly large shift of the peak toward the higher wave numbers due to the perturbation in the structure of lipids of the stratum corneum. The skin bio-liposomes prepared from the rat full thickness skin could be useful in evaluating the penetrants. PMID- 1606650 TI - Plasma-polymerized allylamine film used as a new solid phase in immunoradiometric assay (IRMA): effect of antibody (F(ab')2 fragment) concentration on dose response in two-site IRMA. AB - Allylamine (ALAM) film was plasma-polymerized on a flat glass (referred to as ALAM(GLA): GLA refers to a flat glass plate) for use as a solid phase in two-site immunoradiometric assay (two-site IRMA). Adsorption of F(ab')2 anti-human immunoglobulin G [formula: see text] to ALAM(GLA) was larger than adsorption on a polyvinyl chloride plate (referred to as PVC). Contrary to the expectation that the dose response for human IgG (hIgG) on ALAM (GLA) was better than that on PVC, the dose responses on both solid phases were the same. This phenomenon was independent of molecular size of the antigen (Ag) (hIgG or Fc fragment of hIg G (hIgG-Fc)) and also the reaction with protein A (pA). Because direct measurements of binding with 125I-labeled hIgG (hIgG*) or hIgG-Fc (hIgG-Fc*) showed no difference between ALAM(GLA) and PVC, the phenomenon was not due to the second step in the system of two-site IRMA (an Ag--Ab reaction (Ab refers to antibody)). These results indicated that the phenomenon was due to the first step (the adsorption of [formula: see text] to a solid phase). When the concentration of [formula: see text] immobilized on the solid phases was lowered, a significant increase in the dose response was observed for ALAM(GLA). PMID- 1606651 TI - Effect of pH and guanidine hydrochloride on the conformation of 57 kDa rat liver nuclear thyroid hormone binding protein measured by fluorescence. AB - The denaturation of the 57 kilodalton (kDa) rat liver nuclear thyroid hormone binding protein (NTHB) by pH and guanidine hydrochloride (GdnHCl) has been investigated with the fluorescence method. The acid and alkaline fluorescence quenching suggests that the structure of NTHB is invariant in the relatively narrow pH region of approximately pH 7-9. A cooperative conformational transition occurred in GdnHCl concentrations of 1.5-2.5 m. The apparent free energy of unfolding of NTHB, delta G(appH2O) was evaluated as 6.31 (+/- 0.12) kcal.mol-1 at pH 7.7, 25 degrees C. PMID- 1606652 TI - Zinc deficient bovine erythrocyte superoxide dismutase has low specific activity. AB - Zinc deficient bovine superoxide dismutase (Cu2E2SOD (E = empty)) was prepared and purified by high performance liquid chromatography (HPLC). Each peak was characterized as to protein, copper content and specific activity. The Cu2E2SOD peak fractionated by HPLC has a low specific activity at pH 7.8 (about 10% of the native enzyme (Cu2Zn2SOD)). With the addition of zinc ions, the specific activity of Cu2E2SOD was quantitatively restored to that of the native enzyme. This behavior implies that the zinc ion is very important for the appearance of enzyme activity. PMID- 1606653 TI - Synthesis and antitumor activity of fused quinoline derivatives. II. Novel 4- and 7-hydroxyindolo-[3,2-b]quinolines. AB - Novel indolo[3,2-b]quinoline derivatives (1c--f), which carried a methoxy or a hydroxy group at the 4- or 7-position of the lead compound 1a, were prepared and their antitumor activities against P388 in mice were examined. Except for the 4 hydroxy derivative (1d), these showed remarkably potent activity. Among these compounds, the 7-hydroxy derivative (1f) was the most potent one (optimal dose = 50 mg/kg, the median survival time of treated group/control group (T/C) greater than 330%, cure = 5/6). PMID- 1606654 TI - An enzyme-linked immunosorbent assay for the detection of plasminogen activator induced fribrin clot lysis in a circulating plasma system. AB - A technically easy and sensitive method for the evaluation of the fibrinolytic potency of plasminogen activator in a circulating plasma system was developed. A circulating apparatus was prepared by connecting silicone tubes with two separate chambers. Human plasma and plasminogen activator were allowed to circulate from one chamber through a peristaltic pump into another one which contained biotin labeled fibrin clot. The extent of fibrinolysis was evaluated on streptavidin coated microtiter plates by measuring the amount of the avidin-bound fibrin degradation products with peroxidase-linked antibody. The detection limit of the fibrinolytic products was 1.5 ng/ml. The present method dose not require any specialized equipment and is also applicable to a low-cost routine measurement of the thrombus selectivity of plasminogen activator. PMID- 1606656 TI - Unequal hydrolysis of salicylic acid-D-alanine and salicylic acid-L-alanine conjugate in rabbit intestinal microorganisms. AB - The behavior of salicylic acid-D-alanine conjugate (salicyl-D-alanine) following intravenous, oral and intracecal administration was examined in rabbits, then compared with that of salicylic acid-L-alanine conjugate (salicyl-L-alanine) as reported previously. Following intravenous administration, salicyl-D-alanine eliminated rapidly from the blood, and its blood concentration was almost identical with that of salicyl-L-alanine. In both cases, salicylic acid could not be detected in the blood, indicating that systemic de-conjugation of D-alanine might not occur. Unchanged salicyl-D-alanine was found in the blood mainly following oral and intracecal administration of salicyl-D-alanine. On the other hand, salicylic acid formed extensively following oral and intracecal administration of salicyl-L-alanine, suggesting that the presystemic de conjugation of D-alanine and L-alanine was unequal. Furthermore, in vitro incubation of salicyl-D-alanine with cecal content, in which the major source of salicyl-L-alanine hydrolysis is found, showed that the hydrolysis of salicyl-D alanine was negligible in rabbit intestinal microorganisms. PMID- 1606655 TI - Inhibition of increasing effect of vanadate on glycogen content and lipoprotein lipase activity in fat pads by 5-N,N-hexamethylene amiloride. AB - Sodium orthovanadate (vanadate) increased the glycogen content in isolated rat fat pads in a dose-dependent manner up to 2 mM. Biochanin A, a specific inhibitor of tyrosine kinases, inhibited the increasing effect of vanadate or insulin on both glycogen content and lipoprotein lipase (LPL) activity in fat pads. The increasing effect of vanadate on glycogen content was not decreased by the replacement of Na+ with choline ion in the incubation medium. 5-N,N-Hexamethylene amiloride, a potent inhibitor of the Na+/H+ exchange system, showed a 50% inhibition of the vanadate-increased LPL activity and glycogen content at 25 and 80 microM, respectively, suggesting that mechanisms of the inhibition differ in part between the vanadate actions. Furthermore, a similar inhibitory profile of the vanadate-increased glycogen content was observed with incubation in the presence of absence of Na+ in the medium. These results suggest that the activation of the Na+/H+ exchange system by vanadate is not involved in an increase in the glycogen content in fat pads. PMID- 1606657 TI - Synthesis and antitumor activity of 6-O-carboxymethyl chitin fixing 5 fluorouracils through pentamethylene, monomethylene spacer groups via amide, ester bonds. AB - In order to provide the water-soluble and biodegradable macromolecular prodrug of 5-fluorouracil (5FU), the fixation of 5FUs to 6-O-carboxymethyl chitin(CM-chitin) through pentamethylene, monomethylene spacer groups via amide, ester bonds was carried out. The obtained CM-chitin/5FU conjugate showed the slow release of 5FU and exhibited remarkable antitumor activity against P388 lymphocytic leukemia in mice by intraperitoneal(i.p.) implantation/i.p. injection. PMID- 1606658 TI - Cellular and molecular biology of the cardiovascular system. PMID- 1606659 TI - Subcellular electrolyte alterations during progressive hypoxia and following reoxygenation in isolated neonatal rat ventricular myocytes. AB - This study characterizes the sequential alterations of, and relations between, multiple electrolytes in cytoplasm, mitochondria, and whole cells during hypoxia and on reoxygenation in isolated neonatal rat ventricular myocytes. Subcellular electrolyte content and distribution were measured by electron probe x-ray microanalysis, membrane phospholipid degradation by tritiated arachidonic acid release, and cell morphology by electron microscopy. At 1-2 hours of hypoxia, the myocyte population showed a loss of cytoplasmic potassium, magnesium, and chlorine without alteration of cytoplasmic sodium or calcium. Mitochondria showed increased potassium with unchanged magnesium content. There was no morphological evidence of cell injury or tritiated arachidonic acid release. At 3-5 hours of hypoxia, the myocyte population showed a further loss of cytoplasmic potassium and magnesium and an increase in cytoplasmic sodium, chlorine, and calcium. At a single-cell level, the increase in cytoplasmic sodium preceded the increase in cytoplasmic calcium. Mitochondria showed increased sodium and chlorine and decreased magnesium before increased calcium content; potassium loss was manifest only at 5 hours of hypoxia. At 3-5 hours of hypoxia, there was also tritiated arachidonic acid release and morphological evidence of cell injury. Reoxygenation for 1 hour after 5 hours of hypoxia partially reversed the mean alterations of all electrolytes, except calcium, in the cytoplasm of the myocyte population, whereas analysis was required at a single-cell level to show a partial reversal in calcium levels in cytoplasm of reoxygenated cells. Reoxygenation for 1 hour after 5 hours of hypoxia partially reversed the mean alterations of all electrolytes, including calcium, in the mitochondria of the myocyte population. Recovery of potassium in the cytoplasm correlated with reduction of mitochondrial calcium content on reoxygenation and best predicted recovery of cellular homeostasis of sodium, chlorine, magnesium, and calcium. This study demonstrates that in this experimental model of hypoxia 1) initial losses of cytoplasmic potassium and magnesium occur in the absence of cell injury; 2) increases of sodium, chlorine, and calcium occur in association with cell injury, with sodium increasing before calcium; 3) membrane phospholipid degradation and electrolyte derangement, including increased calcium, may contribute to reversible and irreversible phases of cell injury; 4) analysis of calcium at a subcompartmental level and at a single-cell level is required to correlate reduction of calcium on reoxygenation with recovery of cell homeostasis; 5) reduction of calcium content in mitochondria may predict recovery of cell homeostasis; and 6) recovery of potassium on reoxygenation best predicts recovery of cell membrane function and cell homeostasis. PMID- 1606660 TI - Gap junctional conductance in ventricular myocyte pairs isolated from postischemic rabbit myocardium. AB - Abnormalities of myocardial gap junction-mediated cell coupling have been implicated in cardiac arrhythmogenesis. The potential role of gap junctional dysfunction in the generation of reperfusion-induced arrhythmias is uncertain. The purpose of this study was to measure the effects of myocardial ischemia and reperfusion on gap junctional conductance (gj) between isolated ventricular myocytes. By using a new experimental model, myocyte pairs were isolated from Langendorff-perfused rabbit hearts 1) after 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion, 2) after 75 minutes of control perfusion, or 3) immediately after removal of the heart. Myocytes and myocyte pairs were studied using whole-cell recording techniques. Action potential characteristics of cells in all three groups were normal. Despite similar mean gj in all three groups (0.88 +/- 0.27, 1.15 +/- 0.18, and 1.24 +/- 0.25 microS, respectively; p greater than 0.05), the postischemic group was more widely distributed and had a significantly greater proportion of poorly communicating cell pairs than either control group (gj less than 25% of mean in eight of 15 myocyte pairs versus zero of 15 and one of 13, respectively; p less than 0.02). Thus, postischemic myocyte pairs represent a heterogeneous population of electrically coupled cells in which individual deficits in coupling are masked by a normal mean value. In the reperfused intact heart, local disturbances of cell coupling, similarly undetected by gross measures of conduction, could disrupt myocardial conduction and activation on a microscopic scale and thus enhance arrhythmogenicity. PMID- 1606661 TI - Relation between ventricular and myocyte function with tachycardia-induced cardiomyopathy. AB - Chronic supraventricular tachycardia (SVT) causes left ventricular (LV) dilatation and dysfunction. Changes in myocyte function and structure may be important factors in the development of SVT cardiomyopathy. Accordingly, LV function and isolated myocyte structure and function were examined in six pigs with pacing-induced SVT cardiomyopathy (3 weeks at 240 beats per minute) and six control pigs. LV function was examined by simultaneous echocardiography and catheterization, and isolated myocyte function was studied using computer assisted video microscopy. Indexes of isolated myocyte contractile performance were examined in the unloaded, unattached state (31 control and 24 SVT cells) and after attachment to a basement membrane substrate (65 control and 45 SVT cells). LV fractional shortening and peak +dP/dt significantly decreased in SVT cells compared with control cells (12 +/- 2% versus 28 +/- 2%, and 842 +/- 61 versus 1,216 +/- 119 mm Hg/sec, respectively; p less than 0.05). Isolated myocyte percent shortening and normalized peak velocity of shortening of SVT myocytes adherent to a basement membrane were significantly lower than attached control myocytes (1.2 +/- 0.2% versus 4.3 +/- 0.3%, and 15 +/- 2 versus 37 +/- 5% resting cell length/sec, respectively; p less than 0.05). Similarly, in the unattached state, the extent and velocity of shortening of SVT myocytes were reduced by over 50% from control values. Contractile properties of attached and unattached cardiocytes were also examined in the presence of 2-8 mM extracellular Ca2+. For both attached and unattached SVT myocytes, responsiveness to increases in extracellular Ca2+ were significantly blunted from control values. Ultrastructural examination of SVT myocytes revealed that the percent volume of myofibrils within isolated myocytes was reduced from control values (46 +/- 7% versus 65 +/- 2%, p less than 0.05). In summary, SVT cardiomyopathy is probably due to a primary defect in isolated myocyte contractile performance. The reduced contractile function of SVT cardiomyopathic myocytes was associated with abnormalities in cytoarchitecture and Ca2+ responsiveness. PMID- 1606662 TI - Effects of external pH on ionic currents in smooth muscle cells from the basilar artery of the guinea pig. AB - pHo is an important determinant of vascular tone in cerebral blood vessels. We investigated the effects of changes in pHo on isolated smooth muscle cells from the basilar artery of the guinea pig. Single cells contracted rapidly in response to an elevation in pHo (constant CO2), and contraction was blocked by nifedipine, suggesting a role for dihydropyridine-sensitive Ca2+ channels. In whole-cell patch-clamp experiments, changes in pHo (pHo 5.7-8.1, pHi 7.2 with 10 mM HEPES) strongly affected the amplitude of the peak Ca2+ channel current (10 mM Ba2+, +15 mV, holding potential of -55 mV), with an apparent pK of 6.9. The current-voltage curves were minimally shifted, indicating no important effect of surface charge. To separate the slowly inactivating L-type Ca2+ channel current from the more rapidly inactivating B-type current, the decaying portions of inward currents from cells studied with repetitive 1-second pulses (+15 mV, holding potential of 55 mV) were fit to a two-component model. Titration curves for the L-type and B type currents indicated maximum increases by factors of 3.65 and 1.28 at alkaline pHo and gave apparent pK values of 7.71 and 6.47 (Hill coefficient unity). The time constant of inactivation for the B-type current at +15 mV was little affected by pHo, whereas that for the L-type current increased somewhat with increasing pHo. Additional experiments showed no significant effect of pHo on holding current or on voltage-activated outward currents (pCai 7 with 11 mM EGTA). Our results provide additional evidence for participation of Ca2+ channels in regulating basal tone in cerebral smooth muscle and indicate that pHo regulates current through slowly inactivating, dihydropyridine-sensitive L-type Ca2+ channels. PMID- 1606664 TI - Three types of naturally occurring modified lipoproteins induce intracellular lipid accumulation due to lipoprotein aggregation. AB - Low density lipoprotein (LDL) from patients with coronary atherosclerosis and diabetes mellitus as well as in vitro desialylated LDL, glycosylated LDL, and lipoprotein (a) caused a twofold to fourfold rise in cholesteryl ester in cultured human blood monocytes and intimal smooth muscle cells isolated from normal aorta. Native LDL from healthy subjects failed to induce intracellular lipid accumulation. We have demonstrated by laser correlative photometry and gel filtration chromatography that in vivo and in vitro modified lipoproteins form aggregates under cell culture conditions. The degree of modified lipoprotein aggregation directly correlated with the ability of these lipoproteins to elevate the cholesteryl ester content of cultured cells. Modified lipoprotein aggregates isolated by gel filtration induced a threefold to fivefold elevation in cellular cholesteryl ester content. Aggregates of 125I-modified LDL were taken up and degraded fivefold to sevenfold more effectively as compared with nonaggregated lipoproteins. The uptake and degradation of 125I-labeled aggregates were strongly inhibited by unlabeled aggregates, latex beads, and cytochalasin B but not by native or acetylated LDL. These data indicate that uptake of lipoprotein aggregates occurred by phagocytosis. Obtained results suggest that modified lipoprotein aggregation may be the key condition for lipid accumulation. PMID- 1606663 TI - ATP dependence of calcium uptake by the Na-Ca exchanger of adult heart cells. AB - The ATP dependence of the Na-Ca exchanger was investigated in isolated adult rat heart cells to evaluate the extent to which ATP depletion after a period of ischemia plus reperfusion in whole hearts could limit calcium uptake by Na-Ca exchange. A standard state for measurement of Na-Ca exchange activity that could be used with cells depleted of ATP to different degrees was defined. This was a state of zero sarcolemmal gradient for sodium, potassium, and pH and was achieved by incubation of the cells for 5 minutes with EDTA, EGTA, ouabain, and nigericin. Heterogeneity of cell ATP levels was minimized by using a protocol of total ATP depletion by incubation under conditions similar to ischemia, followed by reoxygenation to give partial restoration of ATP levels. No ATP was regenerated when cells were reoxygenated in the presence of rotenone, and such cells showed a very low rate of calcium uptake. Without rotenone, cells showed an almost complete restoration of Na-Ca exchange activity, in spite of a restoration of ATP levels to only one third of control values. Thus, the dependence of calcium uptake on ATP was highly nonlinear under these conditions. The calculated Km for ATP was no more than 10% of normal ATP levels. We conclude that ATP depletion after ischemia plus reperfusion is unlikely to limit the rate of calcium uptake through Na-Ca exchange in the whole heart if at least one quarter of the ATP is restored. In addition, we measured the apparent ATP dependence of calcium uptake by Na-Ca exchange in cells under conditions in which we previously had concluded that cell ATP distributions were very heterogeneous: when cells undergo contracture during incubation with oligomycin and without glucose. A linear relation between calcium uptake rate and ATP was observed at all ATP levels. This can be understood if cells in contracture that are incubated with oligomycin cannot take up calcium because of low ATP, whereas rod-shaped cells are able to retain a full uptake capability. This result further supports our conclusion that the ATP level declines catastrophically to near zero in these oligomycin incubated cells just before contracture. PMID- 1606665 TI - Gene transfer into coronary arteries of intact animals with a percutaneous balloon catheter. AB - Genetic manipulation of the vasculature may offer insights into the pathogenesis of coronary artery disease and may lead to gene therapy for disorders such as restenosis after percutaneous coronary angioplasty. The goal of this study was to develop a percutaneous method for gene transfer into coronary arteries of intact animals. Liposomes were used to facilitate transfection in coronary arteries with a plasmid containing the cDNA encoding luciferase. This reporter was chosen since it is not expressed in mammalian cells, and it can be quantified using a sensitive assay (light production). Mongrel dogs were catheterized, and DNA was delivered to coronary arteries via a porous perfusion balloon system. Luciferase expression was measured 3-5 days after the procedure, when the dogs were killed. Luciferase activity in control arteries (n = 12) was no higher than average background activity. Eight of 12 transfected arteries exhibited gene expression, averaging 4.3 +/- 2.1 pg luciferase (p less than 0.01, transfected versus control arteries). In addition, the ability to transfect DNA into femoral arteries without a transfection vehicle was tested. Five dogs were subjected to surgical transfection attempts in their femoral arteries with either DNA alone or DNA plus liposomes. Luciferase was expressed in all 10 femoral arteries; those treated with DNA alone expressed 35.6 +/- 8 pg luciferase, and those treated with DNA plus liposomes expressed 42.3 +/- 14 pg luciferase (p = 0.70). These results demonstrate the use of a percutaneous catheter to achieve gene transfer and expression in coronary arteries of intact dogs and suggest that the efficiency of intra-arterial gene transfer may be similar whether or not a transfection vehicle is used. PMID- 1606666 TI - Exclusion of cardiac myosin heavy chain and actin gene involvement in hypertrophic cardiomyopathy of several French families. AB - Familial hypertrophic cardiomyopathy (FHC) is characterized by idiopathic myocardial hypertrophy, which often and predominantly involves the interventricular septum. The disease is transmitted as an autosomal dominant trait, and its major risk is sudden death. It was recently demonstrated that this disease is genetically heterogeneous and that in 13 of 18 unrelated families the morbid locus, termed FHC-1, maps to chromosome 14q11-12 in and/or very near the cardiac beta-myosin heavy chain gene. We have performed linkage analysis with five chromosomal markers detecting polymorphisms in either the cardiac beta myosin heavy chain gene or the cardiac actin gene (located on chromosome 15q) on eight families from different regions of France. We show that 1) it is possible to analyze medium-sized families by using highly informative microsatellite markers located in these genes and 2) the disease is not linked to the two contractile protein genes in any of these families. Moreover, 10-20% of chromosome 14 and 20-40% of chromosome 15 in the vicinity of the respective markers were excluded as possible locations for the morbid locus. These results provide new insights into the identification of the genes responsible for FHC. PMID- 1606667 TI - Role of epicardial mesothelial cells in the modification of phenotype and function of adult rat ventricular myocytes in primary coculture. AB - Adult rat ventricular myocytes undergo a well-documented sequence of phenotypic changes during adaptation to primary culture. However, we observed that coculture of myocytes with a specific subset of nonmyocyte cardiac cells could slow and even reverse the process of adaptation. These nonmyocyte cells were isolated and identified by immunohistochemical and ultrastructural criteria as being of epicardial mesothelial origin. When added to long-term primary cultures of adult ventricular myocytes, epicardial mesothelial cells appeared to induce myofibrillar arrays that were more organized than those seen in noncocultured myocytes; these changes that occurred were concurrent with the appearance of large amplitude contractions and multicellular synchronous beating that was facilitated by gap junctions between myocytes and epicardial mesothelial cells. The changes in morphology and function were accompanied by a marked increase in beta-myosin heavy chain isoform transcription in cocultured myocytes, a return to the ratio of cardiac to skeletal alpha-actin expected in adult rat myocardium, and a much reduced expression of smooth muscle alpha-actin. These changes in myocyte phenotype and function appeared to require epicardial cell-myocyte contact, or close apposition, because media conditioned by epicardial mesothelial cells alone or in coculture had no effect. Thus, these rapid and reversible changes in myocyte ultrastructure, function, and gene expression may provide a useful in vitro model with which to study the mechanism responsible for regulating the plasticity of ventricular myocyte phenotype and the role of specific cell-cell interactions. PMID- 1606668 TI - Changes in intracellular free calcium concentration during long exposures to simulated ischemia in isolated mammalian ventricular muscle. AB - Intracellular free calcium concentration ([Ca2+]i) was measured in isolated ferret ventricular papillary muscles during and after long exposures to ischemia. All experiments were performed at 37 degrees C, and the muscles were stimulated at 1 Hz. Ischemia was simulated by changing from superfusion with oxygenated Tyrode's solution to superfusion with water-saturated gas (95% N2-5% CO2), thus simultaneously stopping oxygenation and restricting the extracellular space. [Ca2+]i was measured with aequorin, which was microinjected into superficial cells of the preparation. Exposure to ischemia caused a complex series of changes in [Ca2+]i. In the first few minutes the changes in [Ca2+]i were variable; however, after approximately 5 minutes all preparations exhibited a progressive increase in amplitude and duration of the stimulated rise in [Ca2+]i (the calcium transient). The amplitude of the calcium transients peaked after approximately 18 minutes of ischemia, when they were 339% of the control value. After this peak, the calcium transients progressively failed to occur in response to stimulation and declined in amplitude; simultaneously, spontaneous oscillations of [Ca2+]i appeared and increased in size and frequency. The oscillations in turn then gradually became less frequent until a large, prolonged (5-10 minute) increase in [Ca2+]i occurred, after which [Ca2+]i returned to a low level. There were no further oscillations after this event, which was seen on average after 37 minutes of ischemia. A slowly progressive contracture often began to develop at about this time. A gradual rise in resting [Ca2+]i occurred during the remainder of the exposure to ischemia. When muscles were reperfused after long exposures to ischemia, there was a very large and prolonged increase in [Ca2+]i, which was usually associated with a contracture and failure of recovery of developed tension. The large increase in [Ca2+]i could be reduced by the inclusion of 3 mM nickel chloride in the reperfusing solution. Comparison between reperfusion with O2 gas versus reperfusion with anoxic Tyrode's solution indicated that reoxygenation was more beneficial to the muscle than resumption of bulk flow. These results reveal the complex spectrum of changes in [Ca2+]i that occur during ischemia and on reperfusion. These changes in [Ca2+]i are likely to play an important role in the generation of ischemic arrhythmias and muscle damage. PMID- 1606669 TI - Verapamil diminishes action potential changes during metabolic inhibition by blocking ATP-regulated potassium currents. AB - Verapamil has beneficial effects on ischemic myocardium, including reduction in electrophysiological derangements, prevention of intracellular K+ loss, and preservation of high-energy phosphates, but the mechanisms underlying these actions are not clear. Recent studies have demonstrated a role of ATP-regulated K+ (KATP) current in action potential shortening and K+ loss during ischemia and metabolic inhibition. Therefore, we studied the effects of verapamil on KATP current in feline ventricular myocytes to test the hypothesis that the drug prevents ischemic electrophysiological disturbances by affecting the KATP channel. Membrane potentials and currents were recorded using standard patch clamp techniques. During 15-minute superfusion with 1 mM CN-, action potential duration measured at 90% repolarization was reduced from 259 +/- 12 to 98 +/- 15 msec (62% reduction) in the absence of verapamil and from 266 +/- 11 to 183 +/- 16 msec (31% reduction) in the presence of 2 microM verapamil (p less than 0.01). In inside-out membrane patches, the KATP current, activated in the absence of ATP, was significantly suppressed by intracellular application of 2 microM verapamil, but the single-channel conductance was not changed. Verapamil did not change the mean open and closed times of the channel within bursts (e.g., the mean open time was 1.92 +/- 0.18 and 1.82 +/- 0.21 msec in the absence and presence of 2 microM verapamil, respectively), but it shortened the mean lifetime of bursts from 41.1 +/- 3.5 to 24.9 +/- 2.8 msec (p less than 0.01) and prolonged the closed time between bursts from 39.4 +/- 4.6 to 78.5 +/- 5.1 msec (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606670 TI - Two methods of examining protein deposits on hydrophilic contact lenses. AB - Our aim in these studies has been to develop spectroscopic techniques for quantitative analysis of the early phases of protein deposition on soft contact lenses. We produced protein deposition in vitro by soaking lenses in a 0.025% chloral hydrate lysozyme solution at 37 degrees C. Two groups of lenses were so treated: one for 15 days and the other for 6 months. The study of in vivo deposits was carried out on lenses used by healthy wearers. From the same six patients we obtained two consecutive groups of 12 lenses: one group worn for 8 hours and the other group worn for 7 days. We tested the lenses by an indirect (destructive) method (based on a colorimetric assay of amino acid complexes obtained by basic hydrolysis) and by a direct (non-destructive) method consisting of spectrophotometry performed on intact lenses. Using the indirect method we found that the lenses absorbed in vitro for 6 months had lysozyme deposits of 5 +/- 1 micrograms; while the lenses adsorbed for 15 days supplied an average of 0.8 +/- 0.3 micrograms of lysozyme. Lenses worn by healthy volunteers show protein deposition equivalent to a lysozyme quantity ranging from 0.8 to 1.6 micrograms. We found a lower limit of detection with the direct method of approximately 5 micrograms, limiting its applicability. PMID- 1606671 TI - Contamination in contact lens care systems. AB - We studied the rate of contamination in the contact lens care systems and conjunctivas of 30 asymptomatic cosmetic soft contact lens wearers. In caring for their lenses, 23 patients used chemical disinfection systems (quaternary ammonium solutions), six patients used hydrogen peroxide, and one used heat. Eighteen patients used unpreserved intravenous saline solution, and only seven patients used commercially prepared preserved saline solutions. Cultures were obtained from lens cases, lens care solutions, and conjunctivas. Contamination was found in 70% of the lens care systems. Fifty-seven percent of the patients had lens case contamination, and 17% had conjunctival contamination. The most frequently isolated bacteria in the lens care systems were Pseudomonas, Staphylococcus epidermidis, and Escherichia coli. We suggest the development of more effective systems for disinfection. PMID- 1606672 TI - Early postkeratoplasty astigmatism following placement of anterior chamber lenses and transsclerally sutured posterior chamber lenses. AB - Intraocular pseudophakic correction during penetrating keratoplasty (PK) for aphakic or pseudophakic bullous keratopathy may be achieved either with anterior or posterior chamber lenses. Posterior chamber lenses can be fixed to the iris or sclera in eyes lacking adequate posterior capsular support. Post-PK astigmatism can delay early visual rehabilitation of the patient. We reviewed the last 15 patients at our institution who had undergone PK and anterior chamber lens placement for bullous keratopathy. These were compared to the last 15 patients who had undergone PK and transsclerally sutured posterior chamber lens placement. Patients who had placement of a flexible anterior chamber lens at time of PK had a mean astigmatism of 6.73 D at the last visit before any sutures were removed. There was no predominant axis of astigmatism or relationship of the axis of astigmatism to the meridian of lens placement. Patients with placement of a transsclerally sutured posterior chamber lens at time of PK had a mean astigmatism of 5.18 D at the last visit before any sutures were removed. Mean astigmatism was not significantly different (P greater than 0.05) from that seen with anterior chamber lens placement. In the majority of patients the axis of post-PK astigmatism was oriented perpendicular to the meridian of the transsclerally sutured posterior chamber lens. PMID- 1606673 TI - A modified technique for conjunctival transplant. AB - An improved technique for the harvesting and placement of conjunctival autograft in complex, advanced and recurrent pterygia is presented. A paper template, fashioned to the approximate size of the pterygium excision site, is used to mark and subsequently transfer the conjunctival graft to the recipient bed. The template creates a strong, steady scaffold on which to orient and align the floppy conjunctival graft. This permits easier suturing and more accurate placement of the graft. We report a series of 30 eyes in which all transplants were taken from the superior or superotemporal bulbar conjunctiva of the same eye. There were no intraoperative or postoperative complications. No graft failures or graft retractions were seen. Although there have been several cases of partial recurrence, we have not had to resort to repeat surgery. We present this modification of a technique originally developed by Thoft and later refined by Vastine and Kenyon, as an effective way to correct complex, advanced, and recurrent pterygia. PMID- 1606675 TI - A case of contact lens related Fusarium solani keratitis. PMID- 1606674 TI - Allergic ocular disorders: a spectrum of diseases. AB - Allergic eye disease is commonly encountered in clinical practice. The external eye is exposed to a host of environmental, cosmetic, and pharmacologic antigens. Although individual responses show a wide range of variability, a number of distinctive syndromes have emerged to define the spectrum of allergic eye disease. They consist of seasonal allergic conjunctivitis (SAC), perennial allergic conjunctivitis (PAC), atopic keratoconjunctivitis (AKC), vernal keratoconjunctivitis (VKC), giant papillary conjunctivitis (GPC), and contact allergies involving the conjunctiva. PMID- 1606676 TI - Do disposable contact lenses really make a difference? PMID- 1606677 TI - Biaspheric lenses in RXD material. PMID- 1606678 TI - Corneal topographic data: its use in fitting aspheric contact lenses. AB - We conducted a retrospective assessment of the fitting characteristics obtained with the Boston Envision rigid gas permeable contact lens to determine the best parameter for selecting an initial base curve. We fit 13 subjects (11 successfully) with the Envision lens, using computerized videokeratoscopy to evaluate prefitting corneal topography. The selected base curve of the lenses fit most closely to the flattest K at the 5 mm zone. This value may be the best parameter for selection of an initial base curve, especially in eyes with keratoconus. Using topographic information may give quicker and more accurate initial fits than keratometry alone. PMID- 1606679 TI - Microbial contamination of hydrophilic contact lenses. Part I: Quantitation of microbes on patient worn-and-handled lenses. AB - We cultured Soflens (polymacon) contact lenses to determine the number of microorganisms present following normal patient wear and handling just prior to disinfection. Total protein deposited was determined for the companion lens from each patient. A random population of 109 adapted soft contact lens patients participated in the study. Some patients participated more than once, resulting in a total of 196 lenses being cultured and 195 lenses analyzed for total protein. The left lens was cultured immediately. The right lens was extracted at 70 degrees C in sodium hydroxide, and the total protein in the extract determined using a modified Lowry protein assay. The mean protein deposition per lens was 3.4 micrograms (median 2 micrograms per lens; range less than 1 to 78 micrograms/lens). Microorganisms were cultured from 95% of the lenses. The mean bacterial count (in colony forming units per lens) was 2,482 (median: 123; range less than 3 to 150,000). Fungal contamination was found on 11% of the lenses at very low levels (3-9 yeast/lens and 3-18 mold/lens). Statistical analysis found no significant relationship between bacterial bioburden and any of the study parameters, including total protein, lens age, or subjective evaluation of lens cleanliness. PMID- 1606680 TI - An evaluation of four multifocal contact lenses in young monocular aphakic patients. AB - To evaluate the efficacy of multifocal contact lenses in the correction of presbyopic symptoms we fit six young monocular aphakic patients with four different bifocal contact lenses (ACC, Tangent Streak, VFL, and Constavu). Each patient had 20/20 uncorrected vision and normal accommodation in the other eye. We evaluated both subjective and objective parameters of comfort and vision for all four lenses. We found no significant overall performance advantage among the four lenses based on comfort, visual satisfaction, visual acuity, contrast sensitivity, or wear-related corneal complications. PMID- 1606681 TI - Argon laser fenestration of a Softperm contact lens. AB - Contact lens fenestration can increase tear exchange. We describe a case in which a patient with 15 D of against-the-rule astigmatism was fit with a Softperm contact lens but was unable to wear it for more than 1 hour because of corneal edema. After fenestrating the Softperm lens with an argon laser the patient was able to wear her lens for 10 hours without signs of corneal decompensation. PMID- 1606682 TI - Physiological effects of tert-butyl hydroperoxide on the rabbit corneal epithelium. AB - Rabbit corneas were mounted atraumatically into an automatic voltage clamp apparatus for the determination of open circuit potential difference and short circuit current. The corneal tissue was bathed on both sides with a Ringer solution, continuously stirred and aerated. After a minimum 1 hour equilibration, a single dose of tert-butyl hydroperoxide (t-BHP) (0.1 mM to 2 mM) was administered to the tear-side solution. This led to an immediate fall in epithelial potential difference and short circuit current. The electrical conductance tended to be subnormal during the peak response. The initial decreases were partially reversed, but even after several hours the majority of corneas sustained abnormal levels of potential difference and conductance. Administration of 2 mM t-BHP to the tearside solution led to an immediate fall in epithelial thickness to -25% of baseline. This was followed by large-amplitude oscillations in corneal epithelial thickness which were sustained over several hours. We conclude that prolonged exposure of the perfused rabbit cornea to small tearside amounts of t-BHP are capable of modulating the electrophysiologic integrity of the corneal epithelium. T-BHP exceeding 1 mM in the tears could compromise the non-catalase dependent antioxidant defense mechanisms in rabbit corneal epithelium. PMID- 1606683 TI - The ontogeny of m1-m5 muscarinic receptor subtypes in rat forebrain. AB - The ontogeny of muscarinic receptor subtypes in rat forebrain has been determined utilizing a panel of antisera recognizing unique epitopes of the m1-m5 receptor proteins. Total receptor density in forebrain, as measured by the non-selective antagonist, [3H]quinuclidinyl benzilate (QNB), was found to increase from 507 fmol/mg in neonates (3.5 days) to 1727 fmol/mg in mature animals (45 days). Adult levels were reached two weeks post-partum. A recently developed precipitation protocol was then used to further characterize receptor ontogeny. Cumulatively, 90% of [3H]QNB labelled muscarinic receptors from adult forebrain were immunoprecipitated with subtype selective antibodies (m1-m5). In 3- to 4-day-old neonates, m1 receptors are expressed at 31% of adult levels, m2 receptors at 32% of adult levels, m3 receptors at 36% of adult levels, and m4 receptors at 20% of adult levels. In mature animals, m1 receptors were equal to 35%, m2 equal to 18%, m3 equal to 11%, and m4 equal to 26%, of total receptors, respectively. Levels of m5 receptors are consistently very low at all ages tested (less than or equal to 1% of total receptor density). Although there were subtle differences in the time courses of development between muscarinic receptor subtypes, in general, they developed with similar ontogenic profiles. Subtypes coupled preferentially to inhibition of adenylate cyclase (m2 and m4) comprised 35% of total receptors expressed in neonates. The combined m2/m4 receptor density increased at a uniform rate during development from 173 to 757 fmol/mg. Receptors preferentially coupled to phosphoinositide turnover (m1, m3, and m5) were found in newborns at approximately 270 fmol/mg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606684 TI - A developmental study of sex and age interactions in the human corpus callosum. AB - Regional analysis of the corpus callosum (CC) has demonstrated that the development of this fiber tract is sexually dimorphic. Midsagittal CC tracings from magnetic resonance images (MRIs) of 73 pairs of age-matched (age 2-79 years) males and females were digitized using computer assisted software. Area, axis length, perimeter, and 99 widths were obtained. Widths were grouped into the following regions based upon prior factor analysis: widths 3-18 (W3-18), W22-39, W49-62, W65-74, W77-85, W89-94, and W95-99. Trend analyses were performed with Sex and Age (blocked into 10-year bins) as independent variables. Higher order Sex by Age interactions were significant in regions W3-18 and W22-39 and were marginal in W95-99. In all 3 regions, females did not attain maximum width until Age 41-50 whereas males had peaked at 20 years and declined thereafter. There were no significant interactions between Sex and Age in the remaining CC regions, nor were there any dramatic decreases once maximum width was reached in adulthood. These results suggest that sex differences may also exist in CC ultrastructure over the human lifespan. PMID- 1606685 TI - Myelination of the cerebral commissures of the hamster, as revealed by a monoclonal antibody specific for oligodendrocytes. AB - Myelination of the cerebral commissures of the hamster was studied by immunostaining with a monoclonal antibody (Rip) specific for oligodendrocytes. Immunostained, preensheathing cells were first observed in the anterior commissure on P6 (P1 = day of birth). By P8, immunopositive oligodendrocytes and myelinated fibers clustered around some of them were detected within the posterior limb of the anterior commissure, ventrally at the rostral half of the callosum, and in the hippocampal commissure. On P12, all the commissures had myelinated fibers throughout their extent, but the callosum and the hippocampal commissure exhibited higher densities of myelinated fibers rostrally. Between P15 and P22, the pattern of myelination approached that of the adult. In the context of other developmental events, myelination of the corpus callosum and of the anterior commissure is a late event, occurring predominantly after stabilization of axon number, either at the end of the progressive accretion of axons, as in the anterior commissure, or after the selective elimination of callosal projections. PMID- 1606686 TI - The expression of CNTF message and immunoreactivity in the central and peripheral nervous system of the rat. AB - We have examined the temporal and spatial expression of ciliary neurotrophic factor (CNTF) and its messenger RNA (mRNA) by immunocytochemistry and Northern blot analysis. Specific CNTF-like (CNTF-IR) immunoreactivity and CNTF message were detected primarily in sciatic nerve, spinal cord, and optic nerve sections in the adult rat. In the sciatic nerve immunostaining was localized primarily to the Schwann cell cytoplasm. Schwann cells in the dorsal root ganglion and in the spinal motor roots were immunoreactive for CNTF but no CNTF immunoreactivity was detected in Schwann cells associated with unmyelinated sympathetic fibers in the superior cervical ganglion. CNTF-IR was first detected in sciatic nerve sections on postnatal day 8 and increased in intensity until reaching adult levels by postnatal day 21. In the adult rat, optic nerve staining was confined to astrocyte-like cells and their projections, and this pattern of immunoreactivity was first apparent at postnatal day 8. Double labelling experiments suggest that a GFAP-positive cell in the optic nerve synthesizes CNTF. In the spinal cord, CNTF-IR was seen only in white matter non-neuronal cells at all ages studied. Branched oligodendrocyte-like cells appeared stained and the staining was first apparent at postnatal day 8. The data, therefore, suggest that myelinating Schwann cells produce CNTF and demonstrate the presence of CNTF and its messenger RNA at the appropriate time period in tissues previously defined as having biological responses to CNTF. PMID- 1606687 TI - 3,5,3'-Triiodothyronine binding sites in synaptosomes from brain of chick embryo. Properties and ontogeny. AB - In this study we have demonstrated the presence of specific 3,5,3'-L triiodothyronine (T3) binding sites in the synaptosomes of chick embryo cerebral cortex and described their ontogeny. Scatchard analyses of binding data obtained with synaptosomal preparations from 17-day-old embryos revealed two T3 binding sites. The first site (N1) had a high affinity and low capacity since its dissociation constant (Kd) was 68 +/- 1.3 nM T3 (mean +/- S.D.; n = 3-5) and its maximal binding capacity (Bmax) was 8.63 +/- 1.59 ng T3/mg of protein, whereas the second site (N2) had a higher Kd of 5.04 +/- 0.5 microM T3 and a larger Bmax of 405 +/- 49 ng T3/mg of protein. The relative affinity of the synaptosomal fraction for T3 and other analogs was the following: T3 greater than T4 (thyroxine) greater than D-T3 (3,5,3'-D-triiodothyronine) = TRIAC (triiodothyroacetic acid) greater than rT3 (reverse T3). Gel chromatography of the [125I]T3 labeled fraction revealed a partially saturable peak with an estimated MW of more than 100 kDa. The ontogenic pattern showed a progressive increase of Kd and Bmax of N1, occurring mainly between the 12 and 19 days of incubation, and a marked fall, particularly of the Bmax, after hatching. The second site did not show any important variation during the embryogenesis. These data indicate the existence of specific T3 binding sites in synaptosomes from cerebral cortex of chick embryo, whose properties and ontogeny are completely different from those of the nuclear receptor.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606688 TI - Rapid development of the auditory brainstem response threshold in individual ferrets. AB - The development of the ferret auditory system was examined using the auditory brainstem response (ABR). Longitudinal recordings were obtained under short acting anaesthesia from individual animals at 4-h or 24-h intervals. Particular attention was focused on the period from postnatal day (P) 26 to P32 when the ferret auditory system becomes functional. ABR thresholds to click stimuli presented in a free-field were found to decline precipitously within a 4-h period during the first 24 h following initial responsiveness. Latencies of waves I and IV of the ABR also declined significantly during this period, but the 'central conduction time' remained stable. A temporal correlation was observed between the time of the precipitous threshold decline and the time of opening of the external ear canal. No changes in cochlear anatomy were observed during this time. We suggest that the opening of the ear canal and/or the clearance of fluid from the middle ear explain the major change in threshold of hearing following onset of function. PMID- 1606689 TI - Ontogeny of epileptogenesis in the rat hippocampus: a study of the influence of GABAergic inhibition. AB - In vivo experiments were carried out to examine whether the period during which gamma-aminobutyric acid (GABA)ergic inhibition in the hippocampus matures is associated with a decrease in epileptogenesis. Seizures were elicited with bipolar electrodes stereotactically positioned in the hippocampus of urethane anesthetized rat pups from postnatal (PN) 7 through 28 days of age. No clinical seizure activity was detected but electrographic seizures (afterdischarges) were induced at all ages. Afterdischarge thresholds (ADT) varied inversely with age. However, the durations of initial afterdischarges and the degree of lengthening of afterdischarges with the rapidly recurring hippocampal seizure (RRHS) protocol were not different for the various age animals studied. Paired pulse inhibition was assessed with a twin pulse paradigm that has been shown to monitor GABAergic inhibition. Measurements were made before and 60 min after a single seizure and again 60 min after the RRHS protocol. At no age was there a significant change in paired pulse inhibition after a single seizure. After RRHS there was a significant reduction of paired pulse inhibition only in the groups that had manifested adult levels of paired pulse inhibition in pre-seizure measurements (greater than or equal to PN 21). These studies indicate that heightened epileptogenesis in the young hippocampus cannot simply be explained on the basis of an immaturity of GABA-mediated inhibition. PMID- 1606690 TI - Developmental dissociation of pharmacological and neurotoxic effects of excitatory amino acids. AB - The development of excitatory amino acid-(EAA)-induced cytotoxic cell death and [3H]gamma-aminobutyric acid ([3H]GABA) release were simultaneously examined in primary cultures of the rat cerebral cortex. Pronounced [3H]GABA release could already be evoked on day 3 by N-methyl-D-aspartate, quisqualate and kainate, whereas toxic cell death could first be induced on day 7, in vitro. EAA-induced GABA release declined between day 11 and 14, but the excitotoxic vulnerability of cells increased further during the same period. This dissociation of releasing and toxic responses indicates that functionally active EAA receptors do not necessarily mediate excitotoxic effects and suggests that the development of EAA receptors mediating release responses precedes the maturation of intracellular mechanisms involved in excitotoxic neuronal injury, at least in cultured cortical neurons. PMID- 1606691 TI - Alterations in dendritic spine density in the rat brain associated with protein malnutrition. AB - Rats that consume a high-protein diet are hyperactive, hyperresponsive to noxious stimuli, and demonstrate elevated basal arousal levels. Although the mechanism involved in dietary protein-induced changes in behavior is unclear, it may involve many changes including abnormal dendrite morphology in the brain. Three groups of rats were pair-fed with isocaloric diets containing 8%, 20% and 50% casein for 4 weeks. Their brains were processed for examination of dendritic spine densities in the frontal, parietal, and entorhinal cortices, the striatum, and the septum. Animals on the 50% casein diet showed increased spine densities in all areas investigated (P less than 0.05), compared to the animals on normal (20%) casein. In contrast, animals maintained on the 8% casein diet showed increased spine densities (P less than 0.05) only in the striatum and entorhinal cortex, and exhibited normal densities in the frontal and parietal cortices, and the medial septum. PMID- 1606692 TI - Localization of microglia in the human fetal cervical spinal cord. AB - Differential morphologic subtypes of microglia have been identified in the human fetal frontal cerebrum using a lectin, Ricinus communis agglutinin 1 (RCA-1), and a monoclonal antibody, EBM-11. In this report, microglia were characterized in the human fetal cervical spinal cord. RCA-1-positive microglia were ramified in the developing gray matter while in the developing white matter they had a less differentiated (ameboid) appearance. EBM-11, a monoclonal antibody that recognizes CD68 on human macrophages, and microglia labeled only ameboid-type microglia in the developing white matter. This suggests that distinct subpopulations of microglia exist, which may represent different stages in microglial development, and that CD68 may be a differentiation marker for less mature forms. Therefore, cytologically less differentiated forms of microglia appear to be associated with myelination. PMID- 1606693 TI - Objective and subjective data for fertile period diagnosis in women: comparison of methods. AB - The Authors have evaluated the reliability of various methods, both natural and biochemical, for the identification of the female ovulatory period in women with regular periods. They compared these methods among themselves and with echographical checking of ovulation. It emerged clearly from the study that the greatest reliability among the natural methods is obtained through the evaluation of the presence of cervical mucus, while among biochemical methods the best results are obtained by a semiquantitative colorimetric test. Brilliant prospects have also been opened by research on saliva. PMID- 1606694 TI - Labour management. Our experience. AB - We report a retrospective analysis of 1202 deliveries assisted by the same medical team, evaluating the clinical management of labour and the resulting type of delivery. Examination of the data revealed a gradual reduction in the number of deliveries treated pharmacologically accompanied by a reduction in the incidence of operative deliveries from 16% to 6%. Statistical analysis of the data using X2 test demonstrated a clear correlation between the administration of oxytocin and the incidence of operative deliveries (p less than or equal to 0.001). We believe that the indiscriminate use of oxytocin in labour should be avoided and that the pharmacological and operative management of labour requires precise clinical indications. PMID- 1606695 TI - The bone sparing effect of oral contraceptive use in non-smoking women. AB - In a group of 30 women, mean age 23.7 years, we have examined the urinary calcium: creatinine ratio (Ca:Cr) as an indicator of bone resorption, before and 6.8 months after oral contraceptive (OC) use. Fasting Ca:Cr decreased significantly during OC use, being more pronounced in nonsmokers. We agree with those who propose the use of OC in women also after 35 years of age, in view of their good effect on bone density. PMID- 1606696 TI - Fertility and conservative treatment in the early stage of cervical cancer. AB - The purpose of this study was to check fertility after the conisation of the cervix. Authors followed-up 74 conized women: 24 became pregnant and of the rest of them, 28 used contraceptive methods and 22 never became pregnant again. 76% of the pregnancies were normal. In only one case, in which the pregnancy was twin, was it necessary to use a cervical cerclage for cervical incontinence. Therefore conisation does not seem to be a limiting factor to fertility. PMID- 1606697 TI - Adolescent triplet pregnancy. AB - The occurrence of spontaneous triplet pregnancy among teenagers is a rare event. The present communication describes two cases encountered at the Mt. Hope Maternity Hospital since its inception in 1981. PMID- 1606698 TI - Induction of labour with prostaglandin gel in patients with unfavourable cervices. AB - 151 primigravid patients with Bishop scores of 4 or less were induced with prostaglandin E2 gel using an initial dose of 2 mg followed by 1 mg or 2 mg at 6 hours. Eighty one patients (53.6 per cent) were in established labour or had delivered by 12 hours, and a further 31 (20.5 per cent) had achieved successful ripening of the cervix. Ninety per cent and 64.5 per cent respectively achieved vaginal delivery and although 39 patients failed to respond to this regime, 72 per cent delivered vaginally after augmentation. No case of hypertonus was recorded and only one patient had abdominal delivery for "failed induction". This regime provides an effective means of induction of labour for a difficult group of patients with little worry of overstimulation and low "failed induction" rates. PMID- 1606699 TI - Meigs' syndrome. A case report. PMID- 1606700 TI - Umbilical blood flow and placental pathology. AB - The aim of the study was to establish whether or not placental morphostructural damage correlates with umbilical artery Doppler waveform and neonatal condition. To this end, seriated ultrasonographic monitoring, flowmeter tests on the cord artery and computerized cardiotocography were carried out in a population of 93 pregnant women in the second half of pregnancy. After birth placentas were subjected to macroscopic and microscopic examination. The Resistance Index showed a good correlation with placental vascular lesions, characterized by a distinct reduction in terminal villi and muscular wall arterioles. Two types of intrauterine growth retardation were discernible, the first of genetic origin with a low-profile growth curve and therefore not amenable to treatment, but with a positive fet l-neonatal prognosis, and the second with a pathologic placental component, presenting a late flattening growth curve with evolution towards fetal distress and a negative fetal-neonatal prognosis. PMID- 1606701 TI - Bozzini and the birth of endoscopy. PMID- 1606702 TI - Effect of spasmoanalgetic Dolantin on the electromyographic activity of the cervix during labour. AB - The influence of spasmoanalgetic Dolantin on electrical activity of the smooth musculature of the cervix during labour was studied in 50 primiparous women after induction of labour. The highest electrical activity was measured at the time of uterine contraction (AC) and between contractions (BC). The basic pattern of Dolantin-produced changes in muscular contractions in the cervix observed via EMG activity is that of the EMG activity diminishing with contractions of the uterine corpus and even more so in the period between contractions. Dolantin administered during the latent phase of induced labour did not accelerate cervical dilatation either in the latent or in the active phase of amniotomy- and Oxytocin-induced labour. PMID- 1606703 TI - A sequential and simple determination of zinc, copper and aluminium in blood samples by inductively coupled plasma atomic emission spectrometry. AB - A sequential method of measuring zinc, copper and aluminium in serum by inductively coupled plasma (ICP) spectrometry is described. It involves a 1/5 dilution of serum with a potassium chloride solution which enhances aluminium signal intensity and reduces variations between different matrix compositions. The method is as sensitive as atomic absorption for zinc (sensitivity: 0.11 mumol/l) and copper (sensitivity: 0.020 mumol/l) and can also be applied to monitor aluminium (sensitivity: 0.12 mumol/l) for patients receiving total nutrition therapy or hemodialysis. Its linearity extends at least to 200 mumol/l for copper and zinc and to 20 mumol/l for aluminium. The correlations with atomic absorption are satisfactory for the 3 parameters, as assessed by the correlation coefficients established for both methods. A reference interval was established with 34 sera of control subjects (19 men, 15 women) which showed an average zinc, copper and aluminium of 14.5 (S.D. 2.6), 17.3 (S.D. 2.1) and 0.32 (S.D. 0.12) mumol/l, respectively. This method does not require a simultaneous ICP spectrometer and can be performed with 1 ml of serum in a single tube, using a routine sequential ICP spectrometer. PMID- 1606704 TI - Relationship of urinary pseudouridine and 1-methyladenosine to activity of leukemia and lymphoma. AB - Urinary levels of pseudouridine and 1-methyladenosine in patients with leukemia and lymphoma were measured by the inhibition ELISA using monoclonal antibodies to determine the correlation of nucleosides excretion with disease activity. Significantly elevated levels of these nucleosides were detected in patients with all types of disease tested. Seventy-seven percent (46/60) and 62% (37/62) of patients had elevated levels of pseudouridine and 1-methyladenosine above normal mean + 2S.D., respectively, and combination assay of these nucleosides gave higher positive rate (87%; 52/60) than either single assay. The changes of urinary pseudouridine and 1-methyladenosine reflected the disease status of patients in remission or in relapse and the effect of chemotherapy. These results suggest that urinary pseudouridine and 1-methyladenosine might be clinically useful as complementary markers to the monitoring of the disease status of patients with leukemia and lymphoma by hematological examination. PMID- 1606706 TI - Organic acids in post-mortem cerebrospinal fluid. AB - Organic acids of cerebrospinal fluid (CSF) have been determined by gas chromatography-mass spectrometry in 29 post-mortem samples obtained from infants and 10 samples obtained from hospitalized children, as controls. Though the organic acids profile was similar in the two groups, eight organic acids not observed in CSF from live infants were inconstantly found in post-mortem CSF and for three of them, malic acid, lactyllactic acid and uracile, concentrations were correlated with the delay in sampling. PMID- 1606705 TI - Creatine kinase MB isoforms for early diagnosis and monitoring of acute myocardial infarction. AB - MB isoforms of creatine kinase (ATP:creatine N-phosphotransferase, EC 2.7.3.2, CK) in 848 sera obtained from 80 patients with acute myocardial infarction (AMI) were studied by agarose gel isoelectric focusing. In 173 sera (20%) from 25 patients (31%), a new isoform designated as MB3 (pI 5.4) was detected at the cathodal side of MB2 (pI 5.2) in addition to the previously known MB2 and MB1 (pI 5.1). The new isoform MB3 was found in the extract of the cardiac muscle. MB3 was dominant in the sera at an earlier stage and a shorter period of time after AMI: 1-14 h (range), 1-29.5 h and 4-154 h for MB3, MB2 and MB1 dominant, respectively. MB3 was therefore found to be an earlier and a shorter phase indicator for AMI than MB2 or MB1. However, MB2 greater than 1 was the most prevalent pattern at the time of admission to the hospital. In AMI, specificity was 96.2%, 92.4% and 90.6%, and sensitivity was 20.4%, 88.9% and 97.6%, for MB3, MB2 and MB1 isoforms, respectively. CK-MB isoform patterns were biased to MB1 dominant in the deceased group, and to MB2 dominant in the surviving group. Therefore determination of CK MB isoforms is also useful in the course of observation of AMI. The fourth isoform, MB0 (pI 5.0), was detected at the anodal side of MB1. MB0 was a minor band of the CK-MB isoform which appeared when serum CK-MB activity increased. PMID- 1606707 TI - Effects of storage, iron and time of day on indices of lipid peroxidation in plasma from healthy volunteers. AB - The concentrations of thiobarbituric acid reactive substances and conjugated dienes in human plasma are often used as indices of lipid peroxidation. However, concentrations of thiobarbituric acid reactive substances in plasma are markedly affected by the iron content of reagents used in the analysis and by storage of samples at -70 degrees C. The assay also has a large interbatch coefficient of variation (14%). Plasma concentrations of conjugated dienes are not affected by storage and the coefficient of variation is only 4%. However, there is a marked diurnal variation in levels of conjugated dienes which is similar to the changes in concentrations of plasma triglycerides. Precise standardisation of analytical procedures is required before these assays can be reliably used in clinical medicine. PMID- 1606708 TI - Use of Toxi-Lab thin layer chromatography in plasma very long chain fatty acid analysis. PMID- 1606709 TI - Improved isolation of mononuclear cells from stored blood. PMID- 1606710 TI - Isodicentric chromosome 18 in an abnormal infant using chromosome specific DNA probe. AB - A report is made on a rare isodicentric chromosome 18 in an abnormal male infant whose karyotype was 46,XY,idic(18)(p11.31----qter), confirmed by in situ hybridization using non-radioactive biotin-labelled 18 probe. His clinical features were similar to 18 trisomy syndrome. The literature concerning isochromosome 18 is reviewed. PMID- 1606711 TI - GM1-gangliosidosis: tandem duplication within exon 3 of beta-galactosidase gene in an infantile patient. AB - A 23-nucleotide tandem duplication (GGACCTTGAAAGTACTC-GGGACC) was found within exon 3 of the beta-galactosidase gene in a patient with infantile-form GM1 gangliosidosis, which generated a premature stop codon after translation of 36 amino acids. Homologous sequences at the area of duplication suggested that the mutation resulted from an unequal crossover. A single base substitution 316Trp--- Cys was found in the other allele. Family study showed that the duplication was transmitted from his father and the base substitution from his mother. PMID- 1606712 TI - Effect of chorionic villus sampling on utilization of prenatal diagnosis in women of advanced maternal age. AB - The effect of the introduction of chorionic villus sampling on the utilization rate of prenatal diagnosis in advanced maternal age was studied during the period 1 January 1985-1 January 1991. On the first of January 1985, the age limit for prenatal diagnosis in The Netherlands was lowered from 38 to 36 years of age. The overall uptake rate during the studied period increased significantly, but only because of the increased uptake rate in the group 36 and 37 years. In the maternal age group of 42 years and older, an uptake rate as low as 15.9% was established. This was mainly determined by the relatively high percentage (73.0%) of women from ethnic minorities in this age group. The number of CVS procedures increased significantly during the study period, but the utilization rate was not influenced, since the number of amniocenteses decreased accordingly. An increase in acceptability of prenatal diagnosis by women of advanced maternal age due to early testing and early termination of pregnancy could not be substantiated in the present study. PMID- 1606713 TI - Concomitant occurrence of mucopolysaccharidosis IIIB and Glanzmann's thrombasthenia. Further evidence of a hyperactive alpha-N-acetylglucosaminidase producing allele. AB - A daughter of first cousins had two extremely rare, recessive disorders: thrombasthenia (Glanzmann's disease, glycoprotein IIb/IIIa deficiency) and mucopolysaccharidosis IIIB, (Sanfilippo B syndrome, alpha-N-acetylglucosaminidase (NAG) deficiency). Normal alpha-N-acetylglucosaminidase activity was observed in two obligate heterozygotes (the proband's father and her maternal grandmother), suggesting that in addition to the normal and defective alleles, a third, hyperactive allele is also present in this family. Such a hyperactive allele seems to be quite prevalent in our area, and makes the biochemical identification of heterozygotes impossible if no extensive family surveys provide additional clues. There was no linkage between the two diseases, nor between any of them and several blood-groups and HLA-antigens tested for. PMID- 1606714 TI - Dominantly inherited microcephaly, short stature and normal intelligence. AB - A large family is reported in which microcephaly and short stature is segregating as a probably autosomal dominantly inherited trait. Some affected members also show a delayed onset of puberty. No other clinical or radiological symptoms are present, and psychomotor development is normal. This short report confirms an earlier description of a similar family by Burton in 1981. PMID- 1606715 TI - Dosage analysis at the CSF1 and CSF1R loci in a new case of partial trisomy 5q. AB - We report on a new case of trisomy for the distal portion of chromosome 5q, arising from a maternal balanced translocation, t(5;22)(q33;q13). The patient presented with mental retardation and peculiar craniofacial anomalies, similar to those already described in trisomy 5q3. Overall, the phenotype bore some resemblance to that of the Brachmann-De Lange syndrome. The extent of the duplicated region was investigated through a combined molecular-cytogenetic approach, using 5q probes for gene dosage analysis by Southern blot, which allowed confirmation of breakpoint assignment to band 5q33. Since most manifestations of trisomy 5q3 are observed in patients with duplications spanning 5q34-qter, it seems that the critical sequences involved in phenotype determination lie within this very distal segment. PMID- 1606716 TI - An additional patient with the 3C syndrome. AB - We report on an 8-month-old child with a dolichocephalic head due to prominent forehead and occiput. Dandy-Walker malformation, cleft palate, congenital heart defect and other minor anomalies. He represents a new case of the 3C syndrome, the fifth described in the medical literature. PMID- 1606717 TI - Cri du chat syndrome due to meiotic recombination in a pericentric inversion 5 carrier. AB - A female infant presented at birth with hypotonia, growth retardation, distinctive facies, multiple congenital anomalies, and a high-pitched mewing cry characteristic of cri du chat syndrome. Chromosome studies from both peripheral blood and fibroblasts showed a 46,XX,5p- karyotype. Parental chromosome studies revealed that the mother carried an apparently balanced pericentric inversion of one chromosome no. 5, 46,XX,inv(5)(p14q35). Meiotic crossing-over in the mother within the inverted segment of chromosome 5 gave rise to the unbalanced karyotype, 46,XX,rec(5)dup q, inv(5)(p14q35)mat in the infant. A small terminal segment of the long arm of chromosome 5 (q35-pter) is duplicated with a deletion of the short arm of chromosome 5 (p14-pter), accounting for the features of cri du chat syndrome. Fewer than 1 in 200 of cri du chat syndrome cases are due to recombination aneusomy arising from a parental inversion of chromosome 5. Some of these cases, however, do not have typical cri du chat syndrome, reflecting significant duplication of 5q material. These cases are reviewed with the present case, and recombination behaviour leading to chromosome imbalance is discussed. PMID- 1606718 TI - Interstitial deletion of 17p11.2 with brain abnormalities. PMID- 1606719 TI - What is clusterin? PMID- 1606720 TI - Clusterin in renal tissue: preferential localization with the terminal complement complex and immunoglobulin deposits in glomeruli. AB - The membrane attack complex (MAC) of complement is activated by immune and non immune mechanisms in the kidney. MAC has been found associated with glomerular immune deposits, but also to cell remnants, particularly along tubules and in vessel walls. Clusterin and S-protein (vitronectin) bind to MAC, rendering it cytolytically inactive. Both have been found associated with MAC in renal tissue. Here we analysed the deposition of clusterin and S-protein in 118 renal biopsies relative to the localization of the MAC using MoAbs. Statistical analysis was performed comparing no or little versus evident or strong staining by immunofluorescence (IF). In glomeruli, out of the 92 biopsies where both MAC and immunoglobulins were evaluated, deposits of MAC were found in the presence (32 out of 41) but also in the absence of immunoglobulins (20/51). Clusterin and S protein deposits were seen, respectively, in 25 out of 61 and 36 out of 61 biopsies containing glomerular MAC, and almost never in its absence (one out of 50 for both). The association of the two inhibitors with MAC was observed mainly in glomeruli containing immunoglobulin deposits (respectively, 21 out of 32 and 25 out of 32), but not when immunoglobulins were absent (three out of 20 and seven out of 20) (coefficient of concordance, K = 0.47 and 0.43). The localization of MAC along tubules and in vessels was easily identified in most biopsies (93 out of 118) and was accompanied by S-protein in most cases (tubules, 86 out of 93; vessels, 82 out of 93) (K = 0.58 and 0.57 respectively) but not by clusterin (28 out of 93 and 24 out of 93). These results suggest that clusterin does not co-localize with MAC whenever there is formation and fixation of the MAC. It seems that clusterin has a particular affinity for MAC which is associated with immunoglobulin. This observation should help to distinguish between the different forms of MAC, and might indicate that MAC associated with immunoglobulin is essentially in its cytolytically inactive form. PMID- 1606721 TI - Increased and prolonged production of specific polymeric IgA after systemic immunization with tetanus toxoid in IgA nephropathy. AB - IgA nephropathy (IgAN) is a chronic form of glomerulonephritis which is characterized by the deposition in the glomerular mesangium of polymeric IgA (pIgA), the source of which is unknown. In order to investigate the production of pIgA in IgAN, patients were immunized systemically with tetanus toxoid (TT). Two weeks after immunization patients and controls responded to TT with an IgA response of similar magnitude. HPLC separation of sera showed that patients with IgAN produce significantly more pIgA anti-TT than controls (7.7 versus 2.88 arbitrary units; P less than 0.04). At this time, 33% of serum IgA anti-TT produced by patients with IgAN was polymeric, compared with 21% produced by controls (P less than 0.02). Monomeric IgA (mIgA) anti-TT levels were similar in both groups. Four weeks after immunization the proportion of pIgA anti-TT in controls and patients was significantly reduced from the 2 week level (from 21% to 0%, P less than 0.02 for controls; and from 33% to 8%, P less than 0.001, for patients). Only four out of 12 controls had any detectable pIgA anti-TT at this time compared with nine out of 10 patients with IgAN (P less than 0.05), and IgAN patients produced proportionally more pIgA anti-TT than did controls (median 8%, interquartile ranges (IQR) 4-10% versus 0% IQR 0-3%; P less than 0.01). HPLC analysis under acid conditions did not alter the pattern of pIgA and mIgA anti TT, suggesting that the high molecular weight IgA fraction was not due to complexes. These data indicate that circulating pIgA results (at least in part) from a systemic response to antigen, which may be exaggerated in IgAN. PMID- 1606722 TI - Soluble IL-2 receptor levels in patients with Graves' ophthalmopathy. AB - In various autoimmune diseases circulating levels of soluble IL-2 receptor (sIL 2R) seem to be related to disease activity. Because reliable parameters of disease activity in Graves' ophthalmopathy are lacking, we measured sIL-2R levels in 47 patients with this disorder. The patients had Graves' disease, but no other immune-mediated diseases, had not yet received specific treatment for their ophthalmopathy and were euthyroid during the entire study period. Twenty-one of the 47 patients (45%) had sIL-2R values above the upper normal limit of 650 U/ml, as established in 20 healthy controls. There were no differences between patients with normal (median 469, range 280-644 U/ml) and elevated (median 946, range 678 1588 U/ml) sIL-2R levels regarding duration or severity of the eye disease (as assessed clinically from the total eye score). However, patients with severely enlarged eye muscles had higher sIL-2R values than patients with less severely enlarged eye muscles on CT scan. Patients with elevated sIL-2R tended to have a higher response rate (71%) to a 3-month course of prednisone, than those with normal levels (46%; P = 0.081). Since a successful outcome of prednisone treatment might be representative for disease activity, the elevated sIL-2R levels seem to reflect active inflammation. Although the practical relevance of this finding in individual patients is limited, it underscores the importance of cell-mediated immune responses in this thyroid-related eye disease. PMID- 1606723 TI - Anti-endothelial cell antibodies in insulin-dependent diabetes mellitus. AB - The prevalence of IgG class antibodies to endothelial cells (AECA) was studied in 136 young patients with insulin-dependent diabetes mellitus by an enzyme immunoassay using human umbilical cord vein endothelial cells. The patients were divided into four groups according to the time between diagnosis and study and their results were compared with those in control children and blood donors. AECA became progressively more frequent with the duration of diabetes, being 4% in diabetics tested within 2 weeks of diagnosis and reaching 34% after an average disease duration of 11.2 years. They were not more common in patients with neuropathy, retinopathy or nephropathy than in patients without these complications, but were associated with co-existing thyroid disease and IgA deficiency. The results suggest that in insulin-dependent diabetes mellitus AECA are associated with co-existing autoimmune disorders but not with diabetic microvascular disease. PMID- 1606724 TI - Prevention of spontaneous and cyclophosphamide-induced diabetes in non-obese diabetic (NOD) mice with oral 2-acetyl-4-tetrahydroxybutylimidazole (THI), a component of caramel colouring III. AB - The effect of oral administration of THI, a compound present in ammonia caramel food colouring, was studied in spontaneous and induced murine diabetes mellitus. Continuous administration of THI at 400 ppm in drinking water reduced the prevalence of spontaneous diabetes in female NOD/Lt mice from 63% in untreated controls to 8% in treated animals. Since cyclophosphamide (CP) accelerates and intensifies diabetes in NOD mice, we also studied the effect of THI in this model. Diabetes incidence was reduced from 100% in mice given only CP to 13-14% in mice given THI either concurrently or from 14 days previously. Histologically, THI greatly reduced the severity of insulitis. As measured by flow cytometry, all THI-treated mice had a 60-80% reduction in splenic CD4+ and CD8+ T cells. THI treated mice showed no untoward effects and specifically no weight loss, or pathological changes in their livers, kidneys or lungs. However, there was moderate atrophy of the thymus cortex. THI is a small imidazole-containing compound with structural similarity to histamine and urocanic acid, both known to have immunosuppressive properties. It is a widely used food additive with no known long-term toxic effects at low dosage. Thus, THI could be a useful immunosuppressive agent. PMID- 1606725 TI - Lymphocytes from patients with rheumatoid arthritis produce agalactosylated IgG in vitro. AB - The percentage of oligosaccharide chains lacking galactose was measured in IgG obtained from pokeweed mitogen-activated cultures of blood lymphocytes from patients with rheumatoid arthritis and controls. Secreted IgG from rheumatoid arthritis lymphocytes was deficient in galactose compared with IgG from the lymphocytes of controls. This confirms that agalactosylation is a significant feature of the disease and demonstrates that it can occur at the B cell level and is not merely a post-secretory event. PMID- 1606726 TI - Limiting-dilution analysis of T cell reactivity to mycobacterial antigens in peripheral blood and synovium from rheumatoid arthritis patients. AB - Limiting-dilution analysis (LDA) was used to quantify the frequency of Mycobacterium bovis BCG- and 65-kD-reactive T cells in paired samples of peripheral blood and synovial tissue from patients with rheumatoid arthritis. The frequency of BCG-reactive T cells detected in the peripheral blood of patients ranged from 1/585 to 1/7639 versus a control frequency range of 1/480 to 1/6773. The frequency of such cells in the synovium was found to be much lower than it was in peripheral blood; in fact, in 80% of patients synovial BCG-reactive T cells were not detected. The frequency of 65-kD-reactive cells in the peripheral blood of each individual was lower than the frequency of BCG-reactive cells (range 1/3738 to 1/55,324), as would be expected. However, no synovial 65-kD reactive cells were detected from any of the patients studied. The LDA assay for the 65-kD antigen was consistent with the single hit model, that for BCG was not. The relatively high proportion of mycobacterial-reactive precursors seen in the peripheral blood of non-vaccinated individuals may reflect a population of cells induced either by natural environmental exposure to mycobacteria or, given the highly conserved nature of heat shock proteins across phylogeny, by some other infection. The results also suggest that the frequent finding of reactivity to proteins such as the 65-kD heat shock protein contained within BCG may not be a generalized phenomenon in rheumatoid synovium. PMID- 1606727 TI - A somatically mutated V kappa IV gene encoding a human rheumatoid factor light chain. AB - The light chain of an IgA kappa rheumatoid factor (RF) produced by a hybridoma derived from a patient with rheumatoid arthritis (RA) has been shown to belong to the V kappa IV family. This RF light chain has 31 nucleotide differences compared with the single V kappa IV germline gene reported for the human genome. The patient's V kappa IV germline gene was sequenced, using the polymerase chain reaction (PCR), and shown to be identical to that previously reported. This demonstrates that the RF light chain is the product of a somatically mutated gene. A comparison with other known V kappa IV sequences shows that the RF light chain has more replacement mutations than most of the known V kappa IV light chains. PMID- 1606728 TI - MHC restriction of synovial fluid lymphocyte responses to the triggering organism in reactive arthritis. Absence of a class I-restricted response. AB - Synovial fluid mononuclear cells (SFMC) from patients with reactive arthritis (ReA) show marked proliferative responses to preparations of the organism triggering the arthritis. Initial studies with MHC-specific MoAbs have indicated that a significant element of these proliferative responses is mediated by class II MHC-restricted CD4+ T cells. It is imperative to establish the presence or absence of a class I-restricted response, for two reasons. Firstly, the association of ReA with the MHC class I molecule, HLA B27, raises the possibility of there being a B27-restricted response to the triggering organism. Secondly, a number of the organisms associated with ReA are intracellular pathogens, whose antigens might be expected to be presented by class I MHC molecules. In an effort to identify a class I MHC-restricted pathogen-specific response in the SFMC of ReA patients, we have assessed the proliferative responses of SFMC depleted of CD4+ T cells. Responses were grossly diminished by CD4+ T cell depletion. We also investigated Chlamydia-specific cytotoxicity in the SFMC of patients with sexually acquired ReA in a system using productive chlamydial infection to produce both targets and effectors. Significant antigen specific cytotoxicity was not seen. These experiments do not provide evidence to support the existence of pathogen-specific responses by CD8+, class I-restricted synovial fluid T cells in ReA. PMID- 1606729 TI - Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells. AB - We investigated whether interferon-gamma (IFN-gamma), interferon-alpha (IFN alpha) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulated synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-gamma (rIFN-gamma), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-alpha and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-alpha and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IFN-gamma, and also inhibited intercellular adhesion molecule-1 (ICAM-1) expression on both endothelial cells and synovial cells stimulated by IFN-gamma. These results suggest that IFN-alpha and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells. PMID- 1606730 TI - Successful transfer of collagen-induced arthritis to severe combined immunodeficient (SCID) mice. AB - We describe the adoptive transfer of erosive arthritis to an immunodeficient host. Spleen cells from arthritic DBA/1 mice (H-2q), immunized 4-6 weeks previously with bovine type II collagen in adjuvant, were transferred intraperitoneally into SCID mice (H-2d). SCID recipient mice also received native or denatured type II collagen (100 micrograms intraperitoneally) at the time of cell transfer. Arthritis developed in five out of five mice approximately 2 weeks after injection of cells plus native collagen, whereas animals injected with cells plus denatured collagen did not show any clinical or histological evidence of arthritis. The minimum graft size required for successful transfer of arthritis was established at 10(7) DBA/1 spleen cells. Histological examination of the joints of arthritic SCID recipient mice revealed synovitis, fibrosis and erosion of cartilage and underlying bone. Mean circulating levels of anti-type II collagen IgG were found to be significantly higher in mice injected with native collagen than those injected with denatured collagen (40 micrograms/ml and less than 1 microgram/ml, respectively). The ability to transfer collagen-induced arthritis adoptively should facilitate the study of the cellular requirement and pathological mechanisms involved in the induction of this arthropathy. PMID- 1606731 TI - Low-affinity antibodies against collagen type II produced by lymph node cells are associated with pathology in collagen-induced arthritis in rats. AB - The relationship between the affinity of antibodies against type II collagen (CII) and arthritis was studied in rats immunized intradermally with bovine CII. Disease was associated with a higher mean titre of serum antibody and a lower mean functional antibody affinity (determined in a chaotropic dissociation assay) against both the immunizing bovine CII and homologous autoantigenic rat CII in comparison with the response in immunized rats that did not develop disease. The functional affinity of the antibodies present in the serum was found to correlate with that of antibodies produced in culture by cells from the lymph nodes draining the site of immunization with collagen. The reduction in mean functional affinity in the anti-collagen response may be the result of the increased production of antibodies of the lowest affinity and a consequent broadening of the affinity heterogeneity. It is proposed that production of low-affinity antibodies in the lymph nodes draining the site of immunization with collagen is important in the pathogenesis of collagen-induced arthritis in rats. PMID- 1606732 TI - Genetic, hormonal and behavioural influence on spontaneously developing arthritis in normal mice. AB - DBA/1 male mice develop arthritis spontaneously at the age of 4 months. The affected joints show cell-rich pannus formation without T cell infiltration and only limited MHC class II expression. Specific pathogen-free DBA/1 mice from different sources developed the same disease. Analyses of inbred mouse strains with various genetic backgrounds and F1 hybrids revealed that the disease is genetically dependent of DBA/1 recessive genes. However, F1 hybrids between DBA/1 and BXSB spontaneously developed arthritis with earlier onset than DBA/1 mice, suggesting that the BXSB autoimmune gene background had both permissive and contributing effects on the development of arthritis. The complete male preponderance for disease susceptibility was investigated by castration and testosterone treatment of DBA/1 males. No arthritis developed after castration and disease susceptibility was restored by testosterone treatment. Arthritis developed only where more than two males were kept in cages, suggesting an influence by aggressive behaviour. Thus, the spontaneous development of arthritis is dependent on hormonal and behavioural mediated effects and differs from experimental models for rheumatoid arthritis such as type II collagen-induced arthritis and pristane-induced arthritis. We conclude that the spontaneously developing arthritis in the normal DBA/1 strain may be more useful as a disease model for osteoarthritis than for rheumatoid arthritis. PMID- 1606733 TI - Effect of lymphocytic infiltration on the blood-retinal barrier in experimental autoimmune uveoretinitis. AB - Using an experimental model of autoimmune uveoretinitis, we have examined the relationship of T cell infiltration in the retina to blood-retinal barrier (BRB) breakdown. Sensitive quantitative in vivo techniques were used to examine BRB permeability to sucrose, a low mol. wt non-transported solute. Electron microscopy was also used to localize extravasated horseradish peroxidase, a macromolecular visual tracer, from the retinal vasculature and to identify the route by which any leakage was occurring. No increase in BRB permeability was found prior to lymphocytic infiltration. By day 10 of the disease inflammatory cells could be seen within the structurally intact retina, which was shortly followed by an increase in the permeability of the BRB to sucrose. Only later in the disease process, when damage to the photoreceptor layer became apparent, did extravasation of the macromolecule HRP occur. At no stage of the disease process was there any detectable damage to inter-endothelial tight junctions. The size dependancy of tracer extravasation in the initial stages of the disease is indicative of a paracellular route being responsible for the increase in BRB permeability. In later stages of the disease some evidence of horseradish peroxidase filled 'vesicle-like' profiles was observed. We suggest that the devastating complication of BRB breakdown in ocular inflammation is a direct consequence of lymphocytic infiltration. PMID- 1606734 TI - Peritoneal macrophages during peritonitis. Phenotypic studies. AB - The expression of a range of surface molecules/receptors that are important in the host response to infection and foreign antigens was examined using peritoneal macrophages isolated from patients on continuous ambulatory peritoneal dialysis (CAPD) with peritonitis. The macrophage phenotypic profile was compared with that of normal peripheral blood monocytes. Consistently there was increased expression by macrophages of CD14, ICAM-1 (CD54), Fc gamma RI (CD64), Fc gamma RII (CDw32), Fc gamma RIII (CD16), transferrin receptors (CD71) and tissue factor. Increased expression of MHC class II was marginally significant. There was no detectable expression of either the p55 (CD25) or p70 chains of the IL-2 receptor. The expression of the complement receptors, CR1 (CD35) and CR3 (CD11b, CD18), was reduced. The activity of well-known inflammatory cytokines, rather than uraemic molecules, can account for the phenotypic profile of these extravasated peritoneal macrophages. The results of this study indicate that peritoneal macrophages from CAPD patients with peritonitis display a phenotype consistent with them being in vivo-derived inflammatory macrophages, and that they are appropriate for use in studies of anti-inflammatory agents. PMID- 1606735 TI - Effect of macrophage activation on killing of Listeria monocytogenes. Roles of reactive oxygen or nitrogen intermediates, rate of phagocytosis, and retention of bacteria in endosomes. AB - The role of macrophage activation in the killing of L. monocytogenes is unclear. Some studies suggest that activation for enhanced production of reactive oxygen and nitrogen intermediates may not be of central importance. Recent data have indicated an important role for interferon-gamma (IFN-gamma) induced retention of L. monocytogenes in endosomes. Data from the present study indicate that proteose peptone-elicited macrophages from DBA2/J, CD-1, and C3H/HeN mice are listericidal. Activation of these cells in vitro for 20 h by IFN-gamma (20 or 500 U/ml) increased H2O2 or nitrite production, but did not increase the number of L. monocytogenes killed during a subsequent 6-h or 7-h culture. Incubation of macrophages with IFN-gamma plus lipopolysaccharide (LPS) caused greater activation and increased the number of Listeria killed during a 6-h or 7-h culture. However, this seems primarily attributable to enhanced phagocytosis. Proteose peptone-elicited macrophages were significantly more effective than resident macrophages in preventing the escape of L. monocytogenes from endosomes into the cytoplasm. This capability was not significantly enhanced by IFN-gamma in vitro, but was enhanced by IFN-gamma plus LPS. This correlates well with the effects of these activation stimuli on killing of L. monocytogenes by proteose peptone-elicited macrophages. These results indicate that enhanced retention of L. monocytogenes in endosomes is induced by proteose peptone elicitation and that further macrophage activation in vitro by IFN-gamma does not improve listericidal activity. PMID- 1606736 TI - Class- and subclass-specific pneumococcal antibody levels and response to immunization after bone marrow transplantation. AB - Immunoglobulin class- and subclass-specific antibodies to a polyvalent pneumococcal capsular polysaccharide vaccine (Pneumovax II) were measured before and after immunization in children, 1 year or more after bone marrow transplantation for a variety of genetic disorders. The median titres of specific IgG, IgG1 and IgG2 pneumococcal antibodies fell significantly (P less than 0.05) from pre-transplantation levels. The levels of pneumococcal antibodies in the patients before immunization were markedly lower than those in control children of comparable age, for antibodies of IgM, IgG, IgG1 and IgG2 classes (P = less than 0.001 in each case). Apart from IgG2 antibodies, the median response to immunization with Pneumovax II was not significantly different from the controls (P greater than 0.05). However, because of the lower pre-immunization levels, the patients did not achieve a high post-immunization-specific antibody titre in any immunoglobulin class or subclass, when compared with normal children. Neither the pre-immunization specific antibody levels nor the response to immunization were affected by splenectomy or the presence of chronic graft-versus-host disease. Immunization of the donor before bone marrow harvest did not influence the level of specific antibody 1 year or more after transplantation. No significant correlation was found between the total serum IgG2, the patients' age at the time of assessment, or time after transplantation, and the IgG2-specific antibody response. The lack of specific antibodies and the poor IgG2 response to pneumococcal antigens may contribute towards the occurrence of infection with Streptococcus pneumoniae in the late post-transplantation period. PMID- 1606737 TI - Genital secretory immune response to chronic simian immunodeficiency virus (SIV) infection: a comparison between intravenously and genitally inoculated rhesus macaques. AB - The humoral and genital secretory immune response to chronic SIV infection was compared between female Rhesus macaques inoculated by i.v. or intravaginal routes. Total IgG levels in serum were 10-fold higher in SIV-infected animals when compared with uninfected controls. Vaginal washes from normal macaques contained predominantly IgA and IgG, while those from SIV-infected animals contained high levels of IgG. The SIV-infected animals had high titres of SIV specific IgG in serum, with lower but detectable IgA and IgM responses. The genital secretory immune response to SIV was similar in intravenously and intravaginally inoculated animals. The anti-SIV response in the vaginal washes consisted mainly of IgG. Within the lamina propria of the reproductive tract of animals chronically infected with SIV there were essentially no IgA or IgG plasma cells and only a small number of IgM plasma cells, while two normal animals had large numbers of IgA plasma cells. These results suggest that the mucosal immune system of the female reproductive tract is impaired in chronic SIV infection. PMID- 1606738 TI - A model for the investigation of factors influencing haemorrhagic necrosis mediated by tumour necrosis factor in tissue sites primed with mycobacterial antigen preparations. AB - Mycobacterial lesions and skin sites challenged with soluble mycobacterial antigen are very sensitive to the necrotizing effect of tumour necrosis factor (TNF). We have used a model that permits separate quantitative assessment of swelling and haemorrhage to show that when these reactions are elicited in mice that have not been deliberately immunized, pretreatment of the mice with lipopolysaccharide (LPS), or with a MoAb to CR3 which blocks emigration of myeloid cells into the tissues, will block both the swelling and the haemorrhage. On the other hand, treatment with an inhibitor of platelet-activating factor (PAF), or with misoprostol (a synthetic prostaglandin E1 analogue), or with cobra venom factor (CVF) which depletes complement, preferentially blocks the haemorrhagic component, while leaving the swelling relatively unaltered. As swelling occurs before the haemorrhage is seen, it is possible that these factors act at a late stage in the cascade of events leading to the tissue damage. However, LPS and CVF were able to inhibit swelling and haemorrhage in the massive reactions elicited in pre-immunized animals, whereas the PAF inhibitor had no detectable effect. PMID- 1606739 TI - Different lymphoid cell populations produce varied levels of neopterin, beta 2 microglobulin and soluble IL-2 receptor when stimulated with IL-2, interferon gamma or tumour necrosis factor-alpha. AB - Immune activation is central to many immune disorders. Clinical investigations have shown that immune activation can be quantified by measurements of soluble immune activation products in serum. Most in vitro studies of these immune activation products have focused on single products. In this study the specific cell sources and the major lymphokines inducing multiple activation products were investigated. In vitro addition of interferon-gamma (IFN-gamma) or IL-2 stimulated peripheral blood mononuclear cells to produce neopterin, beta 2 microglobulin (beta 2-M) and soluble IL-2 receptor (sIL-2R). These two lymphokines can act independently, because neutralizing antibodies to one of the lymphokines did not block the inducing activity of the other. Tumour necrosis factor-alpha (TNF-alpha) was also investigated and shown to be a less powerful inducer than IL-2 or INF-gamma. Separated lymphoid subpopulations responded differently to specific lymphokines. Monocytes produced only neopterin and only in response to INF-gamma. T cells released beta 2-M and sIL-2R in response to IL 2. B cells, however, were capable of producing all three immune activation products. Neopterin production in B cells was induced by either INF-gamma of IL 2, indicating that B cells have additional mechanisms for responding to lymphokines. To investigate whether these in vitro findings also occur in vivo, sera from patients who had received either rIL-2 or INF-gamma treatment were tested. INF-gamma administration led to substantial increases in serum neopterin but only a moderate beta 2-M increase and no increase in the serum sIL-2R levels. rIL-2 administration caused a substantial increase of all three serum immune activation products, consistent with our in vitro findings. The results confirm that increased serum levels of soluble immune activation products are indicators of increased cytokine production by lymphocytes and monocytes and also that B cells can be a prominent source of immune activation products. PMID- 1606740 TI - Neopterin release from human endothelial cells is triggered by interferon-gamma. AB - Human umbilical vein endothelial cells (HUVEC) were investigated for their ability to produce neopterin, a biochemical marker for an activated immune system. Interferon-gamma (IFN-gamma), IL-1 alpha, IL-2, IL-6, tumour necrosis factor-alpha, granulocyte/macrophage colony stimulating factor, phytohaemagglutinin and concanavalin A were used to stimulate HUVEC. While IFN gamma induced neopterin release from HUVEC in a time- and dose-dependent manner, all the other cytokines used had no effect on neopterin production. High neopterin levels are found in patients with rejection episodes or infections. Our results suggest that not only monocytes and macrophages, which are known to synthesize neopterin, but also endothelial cells are responsible for these high serum neopterin levels. PMID- 1606741 TI - Serum-induced suppression of interferon (IFN) activity. Lack of evidence for the presence of specific autoantibodies to IFN-alpha in normal human sera. AB - IgG antibodies binding to different IFN species have been described in sera of healthy and diseased individuals. Human serum immunoglobulins have also been shown to interfere with IFN bioactivity. To characterize these antibodies, human recombinant IFN-alpha 2A (rIFN-alpha) was radioiodinated, and ligand binding studies were performed in human sera as well as on the human cell line A-549 in the presence of human serum. 125I-rIFN-alpha bound to serum factors of healthy individuals. However, less than 3% of the binding was to IgG and the binding was non-saturable and therefore most likely non-specific. 125I-rIFN-alpha bound to receptors on A-549 cells, and the ligand-receptor complexes appeared to internalize. However, both cell binding and internalization of 125I-rIFN-alpha were independent of the presence of human serum. We conclude that normal human sera do not contain detectable autoantibodies to rIFN-alpha. PMID- 1606742 TI - Endothelium-dependent and -independent relaxation by dopamine in the rabbit pulmonary artery. AB - 1. The relaxing response of dopamine (DA) was studied in the rabbit pulmonary artery. DA caused concentration-related relaxation in helically cut strips of the artery contracted with prostaglandin F2 alpha in the presence of prazosin. 2. The DA-induced relaxation in endothelium-denuded strips was reduced to about 40% compared with that in endothelium-intact strips. 3. Methylene blue and haemoglobin, inhibitors of endothelium-dependent relaxation, reduced the DA induced relaxations in endothelium-intact strips to the level of endothelium denuded strips. These results indicate that the DA-induced relaxation is partially mediated or modified by the release of endothelium-derived relaxing factor (EDRF). 4. Apomorphine, as a DA agonist, caused concentration-dependent relaxation in endothelium-intact strips. Bromocriptine, a DA2 agonist, produced only a little relaxation at higher concentration. 5. In endothelium-intact strips, haloperidol, a DA antagonist, and the DA1 antagonists, fluphenazine and SCH 23390 inhibited DA-induced relaxations. On the other hand spiperone and domperidone, DA2 antagonists, were inactive. 6. In endothelium-denuded strips, fluphenazine and SCH 23390 inhibited DA-induced relaxations, but domperidone was inactive. 7. These results indicate that the DA-induced relaxation is mediated by DA receptors, and that DA1 receptors are involved in both endothelium-dependent and -independent relaxation in the rabbit pulmonary artery. PMID- 1606743 TI - Neurovascular function during pregnancy in the spontaneously hypertensive rat. AB - 1. Blood pressure (BP) declines dramatically in the final week of gestation in the pregnant spontaneously hypertensive rat (SHR). This study investigated the hypothesis that alterations of vascular neuroeffector function in the pregnant SHR and normotensive Wistar-Kyoto (WKY) rat are responsible for this decline. 2. Pregnancy in SHR and WKY rats was associated with a significant drop in BP in the last week of gestation. 3. Responses of the perfused mesenteric vasculature to bolus doses of noradrenaline (NA) and potassium chloride (KCl) were decreased in preparations from SHR rats 4 days before delivery. This decreased responsiveness was absent in preparations from SHR rats 1 day before delivery. Responses of the perfused mesenteric vasculature to sympathetic nerve stimulation were not influenced by pregnancy in the SHR. 4. It is concluded that while there are dynamic changes occurring in neurovascular function just prior to delivery, it is unlikely that they are wholly responsible for the dramatic decline in blood pressure in the SHR rat. PMID- 1606744 TI - Cardiac effects of local angiotensin-converting enzyme inhibition in hypertensive patients. AB - 1. The direct cardiac effects of angiotensin-converting enzyme (ACE) inhibitor in 22 hypertensive patients were investigated. Radionuclide ventriculography and echocardiography were performed to measure left ventricular function before and 60 min after administration of a subdepressor dose of captopril. 2. Since the response to ACE inhibitor is not uniform, patients were classified into 12 patients without significant blood pressure change following captopril (group I) and 10 patients with reduction of blood pressure (group II). 3. Clinical and baseline haemodynamic characteristics were similar for the two groups. 4. Ejection fraction (EF) increased without changes of heart rate and end-diastolic dimension after ACE inhibitor in group I as well as group II. The change of EF was not different for the two groups. No correlation was found between changes in EF and blood pressure in group I patients. 5. This study indicates that ACE inhibitor might directly influence left ventricular function independent of systemic haemodynamic changes. PMID- 1606745 TI - Comparison of parathyroid hormone and calcitonin on rat renal calcium and magnesium transport. AB - 1. Because in vitro adenylate cyclase activity studies suggest that parathyroid hormone (PTH) and calcitonin (CT) increase renal tubular calcium and magnesium reabsorption by stimulating the same transport mechanism, the separate and combined effects of these hormones on calcium and magnesium transport was assessed in the rat. 2. Fractional excretion of calcium was 9.5 +/- 0.5% in calcium-infused thyroparathyroidectomized (TPTX) rats and was reduced to 5.1 +/- 0.6 and 4.1 +/- 0.6% by maximal hypocalciuric concentrations of PTH and CT, respectively. 3. Combined administration of maximal PTH and CT produced an effect on fractional and absolute calcium excretion similar to that recorded with maximal CT alone. The combined administration of half-maximal concentrations of PTH and CT also produced a comparable fall in the fractional excretion of calcium to 3.0 +/- 0.7%, which was similar to that observed in the 'maximal CT' and 'maximal PTH plus CT' groups. The magnesium reabsorption data were comparable. 4. These results support biochemical data suggesting that PTH and CT act upon the same transport site, presumably within the thick ascending limb of Henle's loop, to facilitate calcium and magnesium reabsorption. PMID- 1606746 TI - Cimetidine and bradycardia. PMID- 1606747 TI - Cytokines and retroviruses. PMID- 1606748 TI - Psychoneuroimmunology. Commentary. PMID- 1606749 TI - Nomenclature for secreted regulatory proteins of the immune system (interleukins). WHO-IUIS Nomenclature Subcommittee on Interleukin Designation. PMID- 1606750 TI - A canine febrile disorder associated with elevated interleukin-6. AB - Familial Mediterranean Fever (FMF) is a human disorder characterized by recurrent fever of unknown origin (RFUO), renal amyloidosis, and evidence of peritonitis, pleuritis, and/or synovitis. This report suggests that Chinese Shar-pei (CSP) dogs suffer from a similar syndrome. CSP dogs with RFUO (n = 15) showed greater levels of IL-6 in serum than normal controls, hypergammaglobulinemia, and normal or supranormal in vitro lymphocyte blastogenesis in response to mitogen stimulation, when compared to healthy afebrile dogs. In patients 2 years old or older, RFUO was associated with renal failure, renal amyloidosis, and swollen joints. An epidemiological survey of privately owned dogs indicated a RFUO prevalence of 23% in CSP dogs (n = 132) and 1% in dogs of all breeds (n = 98). Increased levels of circulating cytokines, such as IL-6, have been shown to influence such processes as the febrile response, antibody production, and the synthesis of amyloid precursors. We propose that CSP dogs with RFUO, renal amyloidosis, and joint inflammation may serve as an animal model of FMF and that the clinical syndrome is associated with elevated levels of circulating IL-6. PMID- 1606751 TI - Restoration of immunoglobulin secretion in vitro in common variable immunodeficiency by in vivo treatment with polyethylene glycol-conjugated human recombinant interleukin-2. AB - Patients with common variable immunodeficiency (CVI) have decreased immunoglobulin levels resulting in frequent infections. Although previous studies have suggested that the B cell is intrinsically defective, numerous T cell deficiencies, including reduced interleukin-2 (IL-2) production, have been described. Since the addition of T cell cytokines to CVI B cells can increase Ig secretion in vitro, hypogammaglobulinemia in CVI may be due to defective T cell functions. To assess this possibility directly, we treated five CVI patients intravenously with a new biologic, human recombinant IL-2 conjugated to polyethylene glycol. Doses were 250,000 IU/m2 weekly for Weeks 1-4, 500,000 IU/m2 for Weeks 5-8, and 10(6) IU/m2 for Weeks 9-12. During and after treatment, B cells of all patients secreted 10- to 1000-fold more Ig in vitro. There was also a striking improvement in T cell helper activity since T cells of treated patients could induce 10- to 10,000-fold increases in Ig secretion by B cells from normal donors. No increase was seen in serum Igs during the study, but the anti-tetanus antibody of the IgG isotype could be detected in cell culture supernatants. Whether the effects of infused polyethylene glycol IL-2 are mediated through T or B cells, or both, is still unknown. However, these data reinforce the concept that CVI B cells may be competent, but, lacking essential T cell growth factors, in vivo maturation to Ig production does not occur. PMID- 1606752 TI - The respiratory burst of neutrophils, a prognostic parameter in head and neck cancer? AB - Flow cytometric measurements of the respiratory burst of granulocytes (PMN) from 27 patients with advanced carcinomas of the head and neck revealed two types of responses to a stimulus with phorbol myristate acetate (PMA) before, during, and after radiochemotherapy. (1) The majority (74%) of patients responded quantitatively normal (31-fold increase of fluorescence intensity after PMA stimulation, as in controls) but exhibited functional subpopulations in 63% of samples with varying degrees of hyperreactive PMN. (2) A subgroup of 7 patients did not respond to PMA before and during treatment ("nonresponders"), but in two cases responded after therapy. Survival analysis revealed a significantly (P less than 0.02) decreased mean survival time of nonresponders (36 weeks vs greater than 70 weeks in "responders"). Thus, the respiratory burst of PMN could serve as a prognostic parameter in head and neck cancer. PMID- 1606753 TI - On the clinical relevance of psychoneuroimmunology. PMID- 1606754 TI - Postnatal development of T lymphocytes in a novel X-linked immunodeficiency disease. AB - We previously reported an X-linked combined immunodeficiency disease (CID) characterized by immune deficiencies and complicating infections that were more moderate than those found in severe CID (SCID). Since other unstudied males in the family died in infancy, we questioned whether this T cell defect was more profound in early life. Subsequently, the development of blood T cells in an affected newborn male was examined. T cells were virtually undetectable at 48 hr. Over the next several months, CD4+ T cells (principally CD45RO+) rose to levels similar to those found in older affected males, but CD8+ T cells developed more slowly and never attained levels found in other affected males. Thus, this disease in early life mimics SCID and may pose a higher risk of fatal infections to affected individuals during that period. Finally, we speculate that the genetic defect may disrupt intrathymic development or selection of T cells. PMID- 1606755 TI - Systemic immunostimulation after retinal laser treatment in retinitis pigmentosa. AB - Systemic immunostimulation followed an experimental treatment trial of scatter argon laser photocoagulation directed to the retina of one eye of 10 patients with heredo-degenerative retinitis pigmentosa (RP). Significantly increased RP lymphocyte CD25, CD26, and CD4/CD26 activation epitope expressions over prelaser values and controls were found with a normalization of soluble interleukin-2 receptor secretion after laser treatment. Serum interferon-gamma was low both pre and postlaser. Interestingly, when a panel of viral antibodies was tested, only those to rubella virus were elevated in the early postlaser period. The character of RP immunostimulation after laser-induced inflammation could be consistent with an antigenic stimulus from laser-released retinal proteins which might be of autoimmune or latent infectious origin. Enhanced immune responses may be a common but unrecognized sequellae of retinal laser. PMID- 1606757 TI - Potential therapeutic approach for the hormonal treatment of lacrimal gland dysfunction in Sjogren's syndrome. PMID- 1606758 TI - Vulvar diseases. PMID- 1606756 TI - Inhibition of ongoing immunoglobulin production by eosinophil cationic protein. AB - The effect of eosinophil cationic protein (ECP) upon ongoing immunoglobulin (Ig) production and proliferation in human B cells was studied. ECP inhibited Ig production by the human lymphoblastoid cell lines, CBL and GM-1056, in a dose dependent fashion. In contrast, proliferation was not affected. This ECP-induced inhibition of Ig production was specific, since inhibition was blocked by anti ECP serum but not by control serum. Interleukin (IL)-4 did not affect Ig production by CBL or GM-1056 cells; however, IL-4 reversed ECP-induced inhibition of Ig production and this reverse was blocked by anti-IL-4 antibody but not by control antibody. In contrast, other cytokines, including IL-1 beta, IL-2, IL-3, IL-5, IL-6, interferon (IFN)-alpha, and IFN-gamma, failed to reverse inhibition. ECP also inhibited spontaneous Ig production (IgM, IgG1, IgG2, IgG3, IgG4, and IgA) by tonsillar large activated B cells without affecting proliferation. This inhibition was also blocked by anti-ECP serum but not by control serum and was reversed by IL-4 specifically. These results indicate that ECP may play an important role in B cell responses. PMID- 1606759 TI - General principles in the diagnosis and treatment of vulvar diseases. AB - There are several major considerations that compel us to regard the vulva in a special way. Its surface epithelium encompasses a range from mucosa, to keratinized glabrous skin, to keratinized, hair-bearing skin. It thus needs to be approached from the point of view of a dermatologist who has an interest in sexually transmitted diseases and mucosal pathology. Dermatologists have long dealt with another mucosal surface, the mouth, and there are numerous similarities between the two--witness several important orogenital syndromes. The vulva serves both sexual and obstetric functions, so disorders in this area naturally fall in the purview of the obstetrician-gynecologist. What we have attempted to do is to put forth a guide for evaluation and treatment of these patients that is essentially a combination of both approaches. In the authors' experience, we have learned a great deal from each other. We have learned to take a history, examine a patient, and eventually treat her with a combination of dermatologic and gynecologic modalities. If the dermatologist reading this article has become familiar with gynecologic techniques, and the gynecologist with dermatologic techniques, and they have learned when to apply each, we have accomplished our aim. PMID- 1606760 TI - Normal histology and nomenclature of the vulva, and malignant neoplasms, including VIN. AB - In this article, vulvar anatomy and histology are reviewed, and nonneoplastic and neoplastic epithelial disorders are presented. Included are lichen sclerosus, squamous cell hyperplasia, vulvar intraepithelial neoplasia, vulvar Paget's disease, and squamous cell carcinoma. Current terminology, tumor measurements, and staging for vulvar carcinoma are reviewed. PMID- 1606761 TI - Vulvar dermatoses and pruritus vulvae. AB - This article has attempted to summarize the various causes of vulvar pruritus and present a framework for evaluating these patients. Although not all patients have a readily classifiable disorder, symptomatic treatment and reassurance can provide considerable patient relief. There is no easy answer, yet the recognition that the process is treatable, if not curable, should provide encouragement for both patients and their physicians. PMID- 1606762 TI - Lichen sclerosus. AB - Lichen sclerosus is a skin condition affecting all areas of the body at all ages and in both sexes. It appears to be a histologic and clinical entity, although in very many respects it is close to lichen planus and morphea. Its cause and pathogenesis are not established, but a link with autoimmune disease is recognized. Its predilection for the anogenital area in women has led to an unfortunate dichotomy between dermatologists and gynecologists. This was a potent source of confusion for many years but has now been resolved with a the recent formulation of a classification acceptable to the ISSVD (representing gynecologists, dermatologists, and pathologists) and the ISGyP (see Appendices). It is hoped that management will now be more logical, with the mainstay being emollients and topical corticosteroids, and that the vulvectomies sometimes performed for benign disease have become a thing of the past. There is almost certainly an increased risk of malignancy in lichen sclerosus, albeit at present an unquantifiable one, and for that reason patients should be kept under review. PMID- 1606763 TI - Desquamative vulvitis. AB - The typical appearance of inflammatory and bullous diseases may be changed when they occur on the vulva. The moist, warm, occluded environment produces a tendency for the thin skin of the vulva to erode and scar, resulting in a common final appearance often characterized by loss of the labia minora and agglutination of the clitoral hood. The most common diseases that may produce desquamative vulvitis include lichen sclerosus, lichen planus, immunobullous diseases, contact dermatitis, erythema multiforme, lupus erythematosus, and squamous cell carcinoma in situ. The differentiating characteristics and treatment of these diseases are discussed in this article. PMID- 1606764 TI - Vulvovaginitis. AB - Often trivialized by the medical profession, vaginitis in adult women is not only extremely common but the source of considerable stress, and it often results in marked suffering. Epidemiologic studies described in this article indicate the high prevalence of vaginitis and the large number of causes. Although the majority of infections in women are due to BV, VVC, and trichomoniasis, it is clear that many other causes exist, and we have yet to discover the cause of many clinical syndromes. Considerable progress in understanding the pathogenesis of the three common vaginitides has been made. Although excellent progress has been made by the pharmaceutical industry in providing new drugs for vaginitis, any further progress will require a better understanding of cause and pathogenesis. Vaginitis causes major symptoms and is more than a nuisance problem. Clinicians owe it to their patients to make efforts to make an accurate diagnosis and not to rely on empiric therapy. PMID- 1606765 TI - Pigmented lesions of the vulva. AB - Pigmented vulvar lesions, including diffuse hyperpigmentation, are present in 10% to 12% of white women. About 2% of them are nevocellular nevi. In general, nevi on the vulva are identical by morphologic and histopathologic criteria to nevi elsewhere on the body, with the exception of a small subset of nevi in younger women. Nevi in this subset have the unusual features of enlarged junctional nests that are variable in size, shape, and position. The long-term biologic behavior of these nevi has not been determined. Other benign pigmented lesions include lentigines, melanosis, postinflammatory hyperpigmentation, seborrheic keratoses, and warts. Malignant pigmented lesions include some cases of vulvar intraepithelial neoplasia and melanoma. Melanoma of the vulva has a poorer prognosis overall than melanoma on the torso, apparently because of the extent of the disease at the time of diagnosis. Therefore, improving mortality rates depends to some extent on earlier diagnosis. Management of female patients includes careful inspection of the vulva with each full-skin or gynecologic examination, followed by biopsy of any suspicious lesion. The need for excision of benign nevocellular and melanocytic lesions is dependent on the histopathology. Because there are no long-term prospective studies of vulvar melanosis and the group of unusual vulvar nevi, treatment must be individualized. PMID- 1606767 TI - Herpes genitalis. AB - In conclusion, herpes genitalis has become one of the most common sexually transmitted diseases and has reached epidemic proportions. It presents a grave risk to immunocompromised patients and to newborns. The advent of effective therapy with acyclovir has dramatically modified the morbidity and mortality of disseminated herpesvirus infection and has helped in the therapy of primary and recurrent herpes genitalis. Current work has indicated that the disease can be transmitted by asymptomatic patients who are shedding the virus in the absence of visible lesions, which presents a diagnostic and therapeutic problem, especially significant for the pregnant patient, because infection of the neonate leads to serious consequences. Close follow-up of the pregnant woman with genital herpes therefore is imperative to minimize the risk to the newborn. At this time, no vaccines have been demonstrated to be safe and effective; therefore, prevention is of the utmost importance. PMID- 1606766 TI - Sexually transmitted diseases of the vulva. AB - Sexually transmitted disorders may present on the vulva as ulcers, rashes, edema, adenopathy, or pruritus. Clinical and laboratory skills are needed to distinguish one from another so that the proper treatment is selected and further venereal spread is prevented. PMID- 1606768 TI - Vulvodynia. Diagnostic patterns. AB - The symptom of vulvar burning demands special evaluation and management. Possible factors include complications of therapy, inflammatory dermatoses, lichen sclerosus, and infection with organisms such as Candida, human papillomavirus, and herpes simplex virus. Vulvar vestibulitis and dysesthetic vulvodynia or pudendal neuralgia have characteristic patterns of discomfort. Psychological aspects of vulvodynia include the need for supportive therapy. PMID- 1606769 TI - Vulvar vestibulitis syndrome. AB - VVS is currently recognized as one of the leading causes of vulvodynia or chronic vulvar pain. Its cause is unknown, and it is defined by a constellation of signs and symptoms confined to the vulvar vestibule. Hence, there is introital or entry dyspareunia, vestibular erythema of varying degrees, and localized tenderness confined to the vulvar vestibule. It has been found to be associated with subclinical HPV infection; chronic, recurrent candidiasis; and persistent alteration of vaginal pH secretion, and therapy for some of these conditions sometimes leads to amelioration of the symptoms associated with vulvar vestibulitis. The majority of cases, however, are still idiopathic. The more chronic and severe cases are frequently helped by a surgical procedure that results in excision of most of the vestibule and advancement of the vaginal epithelium. Some of the milder cases are known to remit spontaneously, so conservative, supportive management is of the utmost importance. PMID- 1606770 TI - Vulvar manifestations of systemic diseases. AB - As the study of vulvar diseases becomes more accepted and as physicians and patients become more comfortable discussing vulvar complaints, there will also be less hesitancy to examine the area adequately. This can only lead to better observations, more knowledge, and more exact diagnosis and treatment of these problems, whether they be primary in the vulva or part of a systemic process. PMID- 1606771 TI - Diagnosis and therapy for common sexually transmitted diseases. AB - During the past decade, as the human immunodeficiency virus (HIV) has appeared, sexually transmitted diseases (STDs) have resurged to epidemic proportions, and STDs have been shown to facilitate transmission of HIV, the diagnosis and treatment of STDs have increased in importance for all clinicians. This article's recommendations for treatment of STDs that might more commonly be seen in a dermatology practice are based on the 1989 Sexually Transmitted Disease Treatment Guidelines of the Centers for Disease Control. Clinicians are encouraged to address actively prevention and treatment of sexual partners, a very important part of the management of STDs. PMID- 1606772 TI - Randomized controlled trial of cyclophosphamide, warfarin and dipyridamole in idiopathic membranous glomerulonephritis. AB - 40 patients with idiopathic membranous glomerulonephritis were randomized to receive either no treatment or a regime of cyclophosphamide for 6 months, and warfarin and dipyridamole for two years. During the two years of the trial there was no significant deterioration in renal function in either group. A significantly greater improvement in urinary protein excretion was, however, observed at all time points in the treatment group. Plasma albumin was also significantly higher in the treatment group at 18 and 24 months. As progressive deterioration in renal function in membranous glomerulonephritis is associated with persistent heavy proteinuria these results suggest a beneficial effect of treatment. PMID- 1606773 TI - Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy. AB - A retrospective clinicopathological study of 66 patients with IgA nephropathy was undertaken to determine the prognostic significance of various renal histopathological alterations and clinical parameters. At the latest follow-up, after a period of 60 to 72 months following biopsy, 18 patients had serum creatinine concentration above 1.8 mg/dl. When the entire patients were evaluated as a whole, the extents of interstitial broadening and glomerular sclerosis were correlated significantly with the final status of renal function: proteinuria of more than 1.0 g per day and mildly impaired renal function at the time of biopsy were also associated with unfavourable outcome. However, when the patients with initially normal renal function, i.e. serum creatinine level below 1.2 mg/dl, were evaluated separately, the initial amount of proteinuria, but none of the other parameters, had a prognostic significance in the subsequent course of renal function. These findings suggest that proteinuria of more than 1.0 g per day as an early event often indicates the progression of IgA nephropathy, and lead to a postulation that renal histopathological changes become more significant prognostic indicators in the relatively advanced stage of the disease. PMID- 1606774 TI - Association of chronic interstitial cystitis, protein-losing enteropathy and paralytic ileus with seronegative systemic lupus erythematosus: case report and review of the literature. AB - We report the case of a female patient with seronegative lupus and predominant bladder and intestinal involvement in the form of interstitial cystitis and protein-losing enteropathy. This association is exceptional in the literature but may be underestimated because of frequent latency of interstitial cystitis. It may define a peculiar subgroup of lupus patients usually responsive to steroid therapy. In this case, only cyclophosphamide markedly improved the protein-losing enteropathy but did not influence the bladder disease. PMID- 1606775 TI - The spectrum of cardiovascular abnormalities in autosomal dominant polycystic kidney disease: a 10-year follow-up in a five-generation kindred. AB - Clinical, electrocardiographic and echocardiographic data were collected in a group of 228 patients with autosomal dominant polycystic kidney disease (PKD) and in another group of 146 unaffected members (NPKD) both comprised in a five generation kindred followed for 10 years, in order to determine the profile and prevalence of cardiovascular derangement of the genetic disease. A family of 181 members was used as a control. The prevalence of left ventricular hypertrophy in the three groups was 24, 14 and 6% respectively (p less than 0.01); after 10 years it increased up to 35, 26 and 13% respectively (p less than 0.05). The evidence of mitral-valve prolapse was more frequent in PKD and in NPKD group (25 and 20% respectively) than in control subjects (2%) (p less than 0.0001). Mitral incompetence was found in 30, 18 and 8% of those groups respectively (p less than 0.002). The large difference in mitral involvement did not change over time. Tricuspid valve prolapse was detected in 5, 4 and 1% of the three groups, respectively (p less than 0.05). A small increase in frequency was found after 10 years only in polycystic kidney disease patients. Regurgitant aortic lesions were present in higher prevalence in PKD (19%) and NPKD (17%) members than in controls (5%) (p less than 0.001). After 10 years they were 23, 20 and 8%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606776 TI - Outcome of renal transplantation in patients treated with erythropoietin. AB - The introduction of treatment with recombinant human erythropoietin (rhEPO) has raised the possibility of deleterious effects on early kidney graft function. Due to renal anemia, the great majority of patients waiting for kidney transplantation until now have had a low hematocrit. It has been suggested that a low hematocrit is beneficial for early kidney graft function by protecting the transplanted kidney from so-called reperfusion damage, which results in delayed onset of renal function. We have retrospectively examined the early function of 26 kidney grafts transplanted to uremic patients with rhEPO corrected anemia. Compared with a randomized control group no significant differences were seen in the rate of immediate onset of graft function, graft survival or serum levels of creatinine one year after transplantation. We conclude that the reversing of anemia by rhEPO in recipients of cadaver kidneys does not impair early graft function. PMID- 1606778 TI - Comment on "Pharmacokinetics of vancomycin" by Torras et al. PMID- 1606777 TI - A controlled trial of recombinant human erythropoietin and nandrolone decanoate in the treatment of anemia in patients on chronic hemodialysis. AB - We conducted a prospective, randomized study in chronic hemodialysis patients in order to determine whether the erythropoietic response to low dose recombinant human erythropoietin (rHuEpo) could be enhanced by administration with androgens. Patients received rHuEpo 40 U/kg intravenously three times weekly either alone (Group 1, n = 6) or with weekly intramuscular injection of 2 mg/kg nandrolone decanoate (Group 2, n = 6) for up to 16 weeks. Baseline hct, ferritin, N-terminal parathyroid hormone, and aluminum levels were similar. The mean weekly rate of rise in hct was 0.32 +/- 0.13% in Group 1 and 0.37 +/- 0.11% in Group 2, p = NS. Three of 6 patients in Group 1, but only 1 of 6 patients in Group 2, reached the target hct of 30% within 16 weeks. Two patients in Group 2 requested that the nandrolone decanoate be stopped prior to reaching target hct because of unacceptable side effects (acne). We conclude that many chronic hemodialysis patients appear to respond adequately to rHuEpo at the dose used in our study. Nandrolone decanoate does not enhance the response rate to this rHuEpo dose and is associated with significant side effects. PMID- 1606779 TI - Amyloidosis and ankylosing spondylitis. PMID- 1606780 TI - Kidney and HIV-infection. PMID- 1606781 TI - "Pure" meningeal carcinomatosis as the autopsy-proven sole manifestation of an undetected cancer. AB - Meningeal carcinomatosis (MC) was diagnosed in a 37-year-old woman, based on the finding of neoplastic cells in the cerebrospinal fluid. The patient had no relevant antecedent except the resection of a breast "nodule" at the age of 20. No primary cancer nor other metastases were detected, even at autopsy. Histopathology, immunocytochemistry and electron microscopy confirmed pure leptomeningeal infiltration by poorly differentiated adenoepithelial cancer. This case includes several unusual features and raises the possibility of an extremely long-lasting interval between an unrecognized primary (breast?) carcinoma and MC. PMID- 1606782 TI - Unilateral cerebellar hypoplasia. AB - In a 48-year-old man, marked unilateral cerebellar hypoplasia was diagnosed by CT scans and angiographic examinations, later confirmed on autopsy. Clinical findings in cerebellar hypoplasia/aplasia are discussed here, along with the pathogenesis of cerebellar hypoplasia. In this case, several grand mal seizures and persistent headache were the only neurological symptoms. Repeated neurologic explorations did not reveal any abnormality. The clear demonstration of cerebellar hypoplasia associated with ipsilateral hypoplasia of the vertebral artery favors the concept of a vascular genesis of cerebellar hypoplasia/aplasia. PMID- 1606783 TI - Fine needle aspiration biopsy for skull tumors: technical note and two demonstrative case reports. AB - Fine needle aspiration biopsy was performed in two case of infiltrating skull lesions. The role played by this relatively simple procedure in avoiding a major operation is discussed. PMID- 1606784 TI - 28th annual meeting of the Italian Neuropathological Association. Sabaudia, May 21-23, 1992. Abstracts. PMID- 1606785 TI - Controversies in bioequivalence studies. PMID- 1606786 TI - Clinical pharmacokinetics in veterinary medicine. AB - Veterinary and human pharmacology differ principally in the range of species in which drugs are used and studied. In animals, as in humans, an understanding of the dose-effect relationship can be obtained by linking pharmacokinetic behaviour with pharmacodynamic information. Studies of different classes of drugs support the assumption that the range of therapeutic plasma concentrations in animals is generally the same as in humans. The requirement for species differences in dosage or administration rate (dose/dosage interval) may be attributed to variations in pharmacokinetic behaviour or pharmacodynamic activity, or both. When administering a drug orally, the bioavailability from a dosage form can vary widely. This is particularly the case between ruminant animals (cattle, sheep and goats), horses and carnivorous species (dogs and cats). Species variations in bioavailability can be avoided by parenteral administration. Formulation of parenteral preparations and location of intramuscular injection site can, at least in horses and cattle, influence bioavailability. Comparative pharmacokinetic studies help to explain differences in absorption and disposition processes that may underlie species variations in response to fixed dosages of a drug. Certain marker substances are useful in quantifying the activity of metabolic pathways or efficiency of excretion processes. Prediction of preslaughter withdrawal times in food-producing animals represents an application of pharmacokinetics in the field of drug residues. The drug residue profile can be obtained by combining fixed dose pharmacokinetic studies with measurement of drug concentrations in selected tissues and organs of the body. This approach offers an economical advantage in that fewer animals are required for residue studies. In domestic animals, as in humans, the disposition of most drugs can be interpreted in terms of a 2- (generally) or 3-compartment open model. Species variations in pharmacokinetic behaviour of a drug are usually attributed to differences in the rate of elimination rather than distribution and metabolism of the drug, although the principal metabolic pathway may differ. With certain notable exceptions, the herbivorous species (horses and ruminant animals) metabolise lipid-soluble drugs more rapidly than carnivorous species (dogs and cats). Humans metabolise drugs slowly in comparison with animals. Half-life values reflect this; insufficient data are available to base interspecies comparison on mean residence time. Intrinsic hepatic clearance of phenazone (antipyrine) [microsomal oxidation] in humans is approximately one-seventh of that in domestic animals.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606788 TI - Cefotaxime dosage in infants and children. Pharmacokinetic and clinical rationale for an extended dosage interval. AB - Cefotaxime is a third generation cephalosporin antimicrobial agent which has received wide acceptance as a first-line antibiotic for many infections in neonates, infants and children. With an average elimination half-life of about 1 h, cefotaxime is not considered to be a 'long half-life cephalosporin' like ceftriaxone. For this reason, currently accepted dosage regimens for cefotaxime in infants and children employ a dosage of 50 mg/kg every 6 h. Re-examination of the paediatric pharmacokinetic data for cefotaxime and use of simple multiple dose pharmacokinetic simulation of alternative dosage regimens was performed. From this analysis, regimens administering 75 mg/kg of the drug every 8 h or every 12 h were projected to produce serum cefotaxime concentrations adequate to effectively kill many of the common pathogens against which the drug is currently indicated for use in children. The clinical utility of these alternative dosage regimens was supported by a review of the medical literature and examination of the clinical results from studies in neonates, infants and children where cefotaxime was administered in 2 to 3 divided doses daily. It would appear, therefore, that increasing the cefotaxime dosage to 75 mg/kg administered at 8 h intervals would result in less frequent drug administration which would not be expected to compromise safety and efficacy. Alternative dosage regimens for cefotaxime merit further consideration and clinical evaluation before they become commonly used in paediatric therapeutics. PMID- 1606789 TI - Prediction of serum vancomycin concentrations following intraperitoneal loading doses in continuous ambulatory peritoneal dialysis patients with peritonitis. AB - The pharmacokinetics of vancomycin were studied in continuous ambulatory peritoneal dialysis patients with peritonitis. Six patients received an intraperitoneal loading dose of 15 mg/kg and 4 received an intraperitoneal dose of 25 mg/L. The ability of 2 methods to predict serum concentrations during the loading dose exchange was determined. The mean serum concentration after the exchange was 17.8 +/- 2.2 mg/L in patients receiving the loading dose. The mean dialysis clearance in all patients was 0.94 +/- 0.34 L/h. 66.6 +/- 13.4% of a dose was absorbed into the circulation in 4 h. The volume of distribution was 0.61 +/- 0.46 L/kg, and the half-life for equilibration of vancomycin into the circulation from dialysate was 2.76 +/- 0.94 h. Two methods of predicting serum vancomycin concentrations were tested, with 1 method predicting values significantly different from measured concentrations while the other did not. Serum vancomycin concentrations can be accurately predicted during a loading dose exchange. PMID- 1606790 TI - Absorption of high dose furosemide (frusemide) in congestive heart failure. AB - To investigate the influence of the presence of oedema on the pharmacokinetics and pharmacodynamics of furosemide (frusemide) we selected 9 hospitalised patients (mean age 70.3 years, range 59 to 84 years) with severe congestive heart failure (NYHA III to IV) and an assessed amount of peripheral oedema of at least 5 kg. In these patients the absorption of a single oral dose of furosemide 250 mg was studied when their heart failure was decompensated and again, after intensive therapy, when it was clinically compensated. The mean (+/- SEM) weight loss after clinical treatment was 12.0 +/- 2.2 kg. Individual furosemide plasma concentration-time curves could be fitted adequately to a 1-compartment model with 1 first-order absorption and elimination process, in which absorption took place in 2 parts with different lag times. Comparing the decompensated state with the compensated state we did not find significant differences in pharmacodynamics, absorption half-life, elimination half-life, time to peak serum concentration, peak serum concentration itself and area under the plasma concentration-time curve. However, the relative amount of furosemide absorbed in the first fraction was significantly increased after compensation. We conclude that the presence of massive oedema in patients with congestive heart failure has a minor influence on the pharmacokinetics and pharmacodynamics of high dose oral furosemide. PMID- 1606791 TI - The Royal College of Radiologists Multicentre Guideline Study: implications for clinical practice. PMID- 1606792 TI - What are bronchiolitis obliterans organizing pneumonia (BOOP) and cryptogenic organizing pneumonia (COP)? PMID- 1606787 TI - Uses and limitations of positron emission tomography in clinical pharmacokinetics/dynamics (Part II). AB - Positron emission tomography (PET) involves imaging the biodistribution and tissue localisation of small amounts of radiolabelled biomolecules or drugs. In Part I of this article, which appeared in the previous issue of the Journal, the applications of pharmacokinetics in PET were discussed in order to derive quantitative measures of physiological function. Part II examines the use of PET imaging as a tool to study the pharmacokinetics and pharmacodynamics of specific drugs. PMID- 1606793 TI - Bronchiolitis obliterans organizing pneumonia: the clinical and radiological features of seven cases and a review of the literature. AB - The clinical and radiological features of seven cases of bronchiolitis obliterans organizing pneumonia (BOOP) are presented and the literature is reviewed. Six of these cases were idiopathic, one patient had rheumatoid arthritis. Detailed respiratory function tests were available in four cases and showed a restrictive defect with impaired gas transfer. The majority of chest radiographs showed consolidation with no zonal preponderance. One case with unilobar consolidation was mistaken for malignancy. Another case with interstitial shadowing was thought to have cryptogenic fibrosing alveolitis. In those cases with consolidation, it was mainly peripheral. Six of the cases showed good response to oral steroid therapy. Open lung biopsy was the principal means by which tissue was obtained for diagnosis. BOOP should be included in the differential diagnosis of multifocal consolidation. The condition is usually responsive to steroid therapy, so it is important to confirm the diagnosis histologically. PMID- 1606794 TI - The magnetic resonance appearances of the normal thymus in children. AB - The normal thymus in children is highly variable in size and shape. In some cases this has led to the misdiagnosis of mediastinal pathology and an unnecessary thoracotomy. Twenty-five children without suspicion of mediastinal pathology and five children with suspected mediastinal pathology were imaged using magnetic resonance imaging (MRI). MRI is recommended to distinguish between the normal and abnormal thymus in difficult cases where other imaging techniques are inconclusive. PMID- 1606795 TI - The computed tomographic appearances in pulmonary artery atresia. AB - Isolated pulmonary artery atresia is an uncommon congenital abnormality. Plain radiography and ventilation/perfusion lung scintigraphy may suggest the diagnosis but pulmonary angiography has traditionally been recommended for confirmation. The computed tomographic (CT) appearances of four patients with isolated atresia of a pulmonary artery are described. In each case the atretic segment of the abnormal vessel could be identified. Other CT findings included reduction of volume of the involved hemithorax, increased density of the affected lung, a small hilum, and an abnormal pulmonary vascular pattern thought to be due to the collateral systemic arterial supply to the intrapulmonary branches of the atretic pulmonary artery. The diagnosis of isolated pulmonary artery atresia can be made using dynamic, contrast enhanced CT without recourse to more invasive procedures. PMID- 1606796 TI - 245 transaxillary arteriograms in arteriopathic patients: success rate and complications. AB - Two hundred and forty-five transaxillary arteriograms were attempted at Charing Cross Hospital between 1982 and 1991 on 195 arteriopathic patients (mean age 64 years) in whom the femoral route was contra-indicated due to absent pulses (94), previous surgery (108), femoral artery aneurysm (5), severe aorto-iliac disease (8) or previous failure by the femoral route (30). Most arteriograms (211) were carried out to investigate peripheral vascular disease, the others were carried out to perform transluminal angioplasty (16) to assess cerebrovascular disease (10) and to investigate arterial insufficiency of the kidneys, alimentary tract and upper limb (8). There were two (0.8%) technical failures where the axillary artery could not be punctured. Selective catheterization of the carotid, vertebral, axillary, lumbar, renal, superior mesenteric, inferior mesenteric, iliac, femoral or popliteal arteries was performed in the course of 38 procedures. There were three (1.2%) serious complications related to the puncture site, a large haematoma followed by a prolonged neurological deficit of the brachial plexus in a hypertensive patient receiving haemodialysis, and thrombosis of the axillary artery in two other patients both of whom responded to surgical thrombectomy. There were three (1.2%) serious systemic complications, two patients had a cardiac arrest and although both were successfully resuscitated one became anuric and died from renal failure and septicaemia 4 weeks later. One patient with a history of transient ischaemic attacks developed a similar transient episode at the end of the procedure. Compared with six series of 290 attempted brachial artery catheterizations in patients where the femoral route was contra-indicated which have been reported since 1986, our series of 245 attempted axillary artery catheterizations had a significantly higher incidence of technical success at the first attempt (P = 0.021) and a lower incidence of vascular complications requiring surgery or angioplasty which was not statistically significant. Our conclusion is that transaxillary arterial catheterization has a high rate of technical success (99%) and should be considered in patients where the femoral route is contra-indicated due to arterial disease. PMID- 1606797 TI - Contrast enhancing lymph nodes in bladder cancer: a potential pitfall on CT. AB - We report three cases of bladder cancer in which contrast enhanced computed tomography (CT) demonstrated minimally enlarged lymph nodes. These showed uniform uptake of contrast medium to a similar degree as adjacent venous structures, making the distinction between vessels and lymph nodes difficult. Magnetic resonance imaging (MRI) examination resolved the problem in two of the three patients. PMID- 1606798 TI - Skeletal muscle lymphoma. AB - It is rare for lymphoma to present as a primary muscle lesion. The computed tomography (CT) features are described in three cases. Muscle involvement was the only manifestation of lymphoma in two, and in all three cases, contrast enhancement of the soft tissue mass occurred. PMID- 1606799 TI - Sonographically guided coeliac plexus block. AB - A sonographically guided anterior approach to block the coeliac plexus with local anaesthetic was attempted on supine patients before hepatobiliary interventional procedures. A satisfactory block was achieved in 8/9 patients and the minor complication of transient hypotension was encountered in two which were managed conservatively. Comparison with controls showed the coeliac block patients to require significantly less intravenous sedation and analgesia to control pain during these procedures. PMID- 1606800 TI - Comparison of plain radiographs and computed tomographic scanning in nasopharyngeal carcinoma. AB - Plain radiographs, computed tomographic (CT) scans and clinical records of 100 patients with nasopharyngeal carcinoma were studied. CT scans and plain radiographs provided similar information in 46 patients. There were 54 cases in which the two techniques disagreed. In 45 cases CT demonstrated abnormalities not seen in plain radiographs and in nine cases plain radiographs demonstrated abnormalities not seen with CT scanning. Based on the total information gained from clinical examination, the imaging investigations, biopsies, and subsequent clinical course and investigations it appeared that none of the abnormalities predicted by plain radiographs alone could be substantiated. Conversely the CT abnormalities could be supported as being correct. We conclude that CT alone is the undoubted investigation of choice where this is available. Plain films provide less information, are unreliable and, where CT is available, superfluous. PMID- 1606801 TI - Case report: primary lymphoma of bone--MRI appearances with pathological correlation. AB - A case of primary lymphoma of bone involving the proximal tibia is presented. The magnetic resonance (MR) appearances were unusual for a primary malignant tumour, with predominantly low signal intensity on both T1- and T2-weighted images. This correlated with marked fibrosis on histology. These observations are discussed in the context of previous reports of MRI in bone lymphoma. PMID- 1606802 TI - Case report: unusual presentation of splenic hamartoma; computed tomography and ultrasonic findings. AB - Hamartomas of the spleen are rare benign tumours, which are usually asymptomatic, incidental findings at laparotomy or autopsy (Komakl and Gombas, 1976; Brinkley and Lee, 1981; Norowitz and Morehouse, 1989). There are a few well documented reports of symptomatic splenic hamartoma associated with haematological disturbances, marked splenomegaly or even spontaneous rupture that required an emergency operation (Iozzo et al., 1980; Morgenstern et al., 1984). We report a patient with splenic hamartoma who presented with splenomegaly and iron deficiency anaemia. Computed tomographic (CT) and ultrasound (US) evaluation demonstrated an inhomogeneous mass within the enlarged spleen. Malignant melanoma was mistakenly diagnosed by US-guided fine needle aspiration of the mass, and necessitated splenectomy. The final diagnosis was hamartoma of the spleen. PMID- 1606803 TI - Case report: angiosarcoma occurring in a bone infarct. AB - An unusual case of an angiosarcoma that occurred in a bone infarct is presented. A bone infarct may occasionally dedifferentiate to an osteogenic sarcoma or a malignant fibrous histocytoma. However, the association of angiosarcoma with a bone infarct is extremely rare. To the best of our knowledge, there is only one other report of this association in the English literature. PMID- 1606804 TI - Case report: clinical and radiological features of Cogan's syndrome--non syphilitic interstitial keratitis, audiovestibular symptoms and systemic manifestations. AB - The case is presented of a 23-year-old man with Cogan's syndrome, who died from spontaneous rupture of a renal artery 2 years after developing symptoms, despite treatment with corticosteroids and azathioprine. The typical clinical features, investigations and radiological findings of this rare disease are described, particularly the systemic vasculitis and its angiographic and ultrasound appearances. PMID- 1606805 TI - Case report: primary mesenchymal chondrosarcoma of the brain. AB - We report an 11-year-old girl with a very rare tumour, mesenchymal chondrosarcoma of the brain, presenting as a haemorrhagic stroke, in whom angiography originally showed a distal arterial aneurysm. One month later MRI showed a solid tumour in addition to evidence of haemorrhage, and angiography then demonstrated pathological vascularity. The diagnosis was made following craniotomy. PMID- 1606806 TI - Case report: oily contrast seen in the subarachnoid spaces--a late sequel of a complication of amniofetography. AB - Droplets of oil-based contrast medium were unexpectedly seen within the head of a 14-year-old girl being investigated for headache. The contrast had been inadvertently introduced during an attempted amniofetogram whilst the patient was in utero. As far as the author is aware, this complication of amniography and its late sequel has not previously been reported. PMID- 1606807 TI - Childhood achalasia. PMID- 1606808 TI - The laser Doppler analysis of posturally induced changes in skin blood flow at elevated temperatures. AB - Recently, it has become possible to use laser Doppler techniques to separately quantitate the two components of blood flow, microvascular volume and red blood cell velocity. We used these techniques in 21 normal volunteers to quantitate the effect of postural changes in skin blood flow and its components at 35 degrees C and at 44 degrees C. Postural skin blood flow changes have ben studied extensively at basal skin temperature, but not at elevated temperatures. We contrasted changes at sites with arteriovenous anastomotic (AVA) blood flow (toe and finger pulps) with changes at sites with primarily nutritive flow (elbow and knee). Skin blood flow increased markedly with increasing temperature. The increases at the elbow and knee were the products of equivalent increases in both microvascular volume and velocity. In contrast, the increases on the finger and toe pulps were mainly due to increases in velocity. Elevation of both upper and lower extremities brought about a decrease in skin blood flow. Dependency increased blood flow. The magnitudes of observed changes were greater on the lower extremity than on the upper extremity and greater at 44 degrees C than at 35 degrees C. Once again, with postural change, the nutritive areas exhibited similar changes in volume and velocity while the AVA areas primarily showed velocity alterations. The correlation of systolic pulse pressures with blood flow was greater at the AVA areas than at nutritive areas and greater at 44 degrees C than at 35 degrees C. This correlation was with the velocity rather than with the volume component.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606809 TI - Assessment of the composition of major body regions by dual-energy X-ray absorptiometry (DEXA), with special reference to limb muscle mass. AB - Dual-energy X-ray absorptiometry (DEXA) has been used to assess and compare the composition of whole body and major body regions in 12 female (weight, 56.9 +/- 6.2 kg; BMI, 17-25 kg m-2) and 16 male (weight, 73.1 +/- 9.6 kg; BMI, 20-28 kg m 2) healthy subjects. Standard deviations (and % coefficients of variation) of the differences between repeated measurements of fat ranged from 0.11 kg (9.0%) for arms to 0.42 kg (3.0%) for whole body; for arm bone mineral, 0.01 kg (2.0%), and for fat-free soft tissue of the whole body, 0.42 kg (0.8%). Limb muscle mass was estimated using a new theoretical model of body composition, and the corresponding precision ranged from 0.15 kg (3.8%) to 0.27 kg (1.5%) for arms and total limb muscle mass, respectively. Proportions of each region consisting of fat were greater in females than in males (range, 20-31% vs. 16-18%), respectively, but the ratio of trunk to leg fat was lower (34:49% vs. 46:38%, respectively). Regional proportions of bone were similar between the sexes (all in the range 2.9-5.6%, for both females and males). Mean total limb muscle masses were 14.2 kg (arms, 2.8 kg; legs, 11.4 kg) for females and 22.2 kg (arms, 4.8 kg; legs, 17.4 kg) for males, which were 33.6% and 36.0% of fat-free mass, respectively. The correlation coefficients between limb muscle (DEXA) and other indices of muscle mass were: for DEXA vs. total body potassium, 0.90 (SEE 1.1 kg muscle mass) to 0.94 (1.6 kg); and for DEXA vs. anthropometry, 0.43 (1.2 kg) to 0.85 (1.3 kg). Those for limb volume (DEXA) vs. anthropometric volume, 0.91 (0.78 1) to 0.94 (1.91 1). It is concluded that DEXA enables the valid and reproducible estimation of fat, fat-free soft tissue, bone, and limb muscle mass. PMID- 1606810 TI - Presyncope caused by central hypovolaemia is not preceded by evoked potential alterations. AB - The mechanism(s) responsible for the onset of presyncope during a central hypovolaemic challenge have gone undefined for many years. It has been speculated that a decrease in cerebral blood flow initiates presyncopal responses, which in turn lead to greater decreases in cerebral oxygen delivery and unconsciousness. Somatosensory evoked potentials (SEP) were monitored as a measure of cerebral functioning in ten subjects during presyncopal symptom limiting lower body negative pressure (a central hypovolaemic challenge). SEP latency and amplitudes have been correlated with cerebral oxygen uptake, so SEP activity can serve as an indirect indicator of cerebral homeostasis. SEPs were generated by electrically stimulating the median nerve and recoding the resulting potentials over the contralateral cerebral cortex. While heart rate and mean blood pressure both fell at presyncope, there were no changes noted in either SEP latency or amplitude at any point before (latency = 22.9 +/- 9 ms; amplitude = 2.86 +/- 0.24 microV), during (22.6 +/- 0.9 ms; 2.68 +/- 0.2 microV), or after (22.7 +/- 0.9 ms; 2.37 +/ 0.23 microV) the occurrence of presyncope. We conclude that the onset of presyncope is not associated with a decrease in cerebral function. PMID- 1606811 TI - Short-term starvation decreases skeletal muscle protein synthesis rate in man. AB - The rate of protein synthesis in skeletal muscle was determined in the post absorptive state and after 3 days of starvation in healthy volunteers. The flooding dose technique employing intravenous injection of (1-13C)leucine (0.05 g kg-1) was used and incorporation of isotope into muscle protein was measured by taking percutaneous biopsies at 0 and 90 min. Blood samples were taken during the incorporation period for assessment of the enrichment of the free amino acid precursor of protein synthesis. The median (25,75 quartiles) rate of muscle protein synthesis after an overnight fast was 2.03 (2.00,2.23) % days-1 when the precursor enrichment was obtained by measurement of the plasma alpha ketoisocaproate, taken to be representative of muscle free leucine. Repeat measurements in the same subjects after 3 days of total starvation showed a decrease to 1.82 (1.57,2.05) % days-1. Rates calculated on the basis of the plasma leucine as precursor were 5% lower at both times. An interindividual variation in response to starvation was observed, but the median decrease of 13% in the rate of protein synthesis was statistically significant (P less than 0.01). PMID- 1606812 TI - Evaluation of non-respiratory function of the human lung by HIPDM lung scanning. PMID- 1606813 TI - Recent developments in computer analysis of ECGs. PMID- 1606814 TI - Late potentials--a clinical update. PMID- 1606815 TI - Biomagnetic multi-channel systems. Principles and application in cardiology. AB - The non-invasive measurement of the extremely weak magnetic fields generated by heart and brain is motivated by the possibility of obtaining quantitative diagnostic information about electric function. Magnetic signals (MCG, MEG) are significantly less influenced by body tissue than the corresponding electric signals (ECG, EEG). Measurement of biomagnetic signals is performed by superconducting sensors, consisting of pickup coils and SQUIDs (superconducting quantum interference device) operating in liquid Helium. For clinical investigations a biomagnetic multi-channel system (KRENIKONR) has been designed. It uses a flat array of 37 magnetic field sensors and is operated inside a shielded room. Evaluation of biomagnetic signals by use of simple source and body models and in combination with anatomical data from 3D MR- or CT-images yields sequences of locations of electrical function with a spatial resolution of some millimeters and a time resolution better than one millisecond. More than three years of clinical studies have demonstrated the value of the method primarily in cases with localized functional pathologies. In cardiology this is pathologies of the cardiac conductive pathway, ectopies, and arrhythmias. Validation has been performed by catheter stimulation in volunteers, and by catheter mapping and nuclear medical methods in patients. Extension of modelling and evaluation to cases with distributed activity, e.g. ventricular excitation, is under investigation. PMID- 1606816 TI - Lung function in fire fighters. AB - Lung function tests were performed on 49 fire fighters of the city of New Haven. Their mean age was 36.4 years, with a mean of 11.7 years as fire fighters. The lung function tests were compared to a control group with a mean age of 33.4 years. There was no significant difference between the mean normal pulmonary function tests of the fire fighters and the control group. The results showed that in this group of fire fighters long-term occupational exposure was not associated with pulmonary function abnormalities. PMID- 1606817 TI - Thiazide-induced pulmonary edema: a case report. AB - A 42-year-old white female developed severe respiratory distress 30 minutes following the ingestion of hydrochlorothiazide. On her arrival at the emergency room, pulmonary edema was evident by physical examination and chest radiograph. She presented without evidence of a gallop, jugular venous distention, or history suggesting cardiac disease. Normal electrocardiogram (ECG) and echocardiogram, and a radionuclide ventriculogram showing normal systolic and diastolic functions supported the noncardiac origin. The patient responded to supportive treatment within hours although the radiographic abnormalities persisted for several days. A review of the literature revealed that at least 12 other cases have been described of this unusual but life threatening idiosyncratic reaction to hydrochlorothiazide. PMID- 1606818 TI - Getting a good history. PMID- 1606819 TI - Managed care: 'the hassle factor,' by choice or coercion. PMID- 1606820 TI - PIAA closed claim studies breast cancer and colon cancer results. Connecticut Medical Insurance Company. PMID- 1606821 TI - Unexpectedly large 1992 transition payment cuts. American Medical Association. PMID- 1606822 TI - Is the primary care physician to be kept out of the hospital? PMID- 1606823 TI - Medical advisor in the Office of the State Commissioner of Welfare. PMID- 1606824 TI - Benjamin Rush, M.D.--doctor and patriot, 1745-1813. PMID- 1606825 TI - Confronting futile care: overcoming the barriers. PMID- 1606826 TI - Status of cryopreservation of embryos from domestic animals. AB - The discovery of glycerol as an effective cryoprotectant for spermatozoa led to research on cryopreservation of embryos. The first successful offspring from frozen-thawed embryos were reported in the mouse and later in other laboratory animals. Subsequently, these techniques were applied to domestic animals. Research in cryopreservation techniques have included studies concerning the type and concentration of cryoprotectant, cooling and freezing rates, seeding and plunging temperatures, thawing temperatures and rates, and methods of cryoprotectant removal. To date, successful results based on pregnancy rates have been obtained with cryopreserved cow, sheep, goat, and horse embryos but no success has been reported in swine. Post-thaw embryo survival has been shown to be dependent on the initial embryo quality, developmental stage, and species. The freezing techniques most frequently used in research and by commercial companies are identified as "equilibrium" cryopreservation. In this technique the embryos are placed in a concentrated glycerol solution (1.4 M in PBS supplemented with BSA) at room temperature and the glycerol is allowed to equilibrate for a 20-min period. During the cooling process the straws are seeded (-4 to -7 degrees C) and cooling is continued at a rate of 0.3 to 0.5 degree C/min to -30 degrees C when bovine embryos may be plunged into LN2. Sheep embryos are successfully frozen with ethylene glycol (1.5 M) or DMSO (1.5 M) rather than with glycerol. Horse embryos have been frozen in 0.5 rather than 0.25 cc straws but with cooling rates and seeding and plunging temperatures similar to those used with bovine embryos. Swine embryos have shown a high sensitivity to temperature and cryoprotectants probably due to their high lipid content and a temperature decrease to 15 or 10 degrees C causes a dramatic increase in the percentage of degenerated embryos. However, a recent study has shown that hatched pig blastocysts survived exposure below 15 degrees C. Recent research has shown that embryos may also be frozen by a "nonequilibrium" method. This rapid freezing by vitrification consists of dehydration of the embryo at room temperature by a very highly concentrated vitrification media (3.5 to 4.0 M) and a very rapid freeze that avoids the formation of ice allowing the solution to change from a liquid to a glassy state. Vitrification solutions consist of combinations of sucrose, glycerol, and propylene glycol. With this technique, 50% pregnancy rates have been reported with the bovine blastocyst. PMID- 1606827 TI - A mechanism of latent cryoinjury and reparation of mitochondria. AB - Changes in the systems of oxidative phosphorylation and ion transport of rat liver mitochondria have been studied during storage or incubation after freeze thawing. It has been found that two different processes take place in frozen thawed mitochondria, one of them tends toward resealing membrane defects and is accompanied by a partial reparation of function; and another one leads to a decrease of the membrane potential, release of K+ and Ca2+ from the matrix, accumulation of lipid peroxides, and uncoupling of oxidative phosphorylation (latent cryoinjury). The latent cryoinjury appears as a result of oxidation of endogenous pyridine nucleotides under conditions of high permeability of the inner membrane and low membrane potential, thus causing activation of the membrane lipid peroxidation and enzyme hydrolysis, leakage of cations, and deenergization of mitochondria. Inhibition of the latent cryoinjury favors the restoration of mitochondrial function after freeze-thawing. PMID- 1606828 TI - Potential contribution of cryopreserved germ plasm to the preservation of genetic diversity and conservation of endangered species in captivity. AB - Demographic and genetic objectives of captive propagation programs for endangered species focus on establishing demographically secure populations that maintain adequate levels of genetic diversity. Long-term storage and utilization of cryopreserved germ plasm could extend the population's generation length and allow higher levels of genetic variation to be maintained in smaller populations. Since fewer breeding animals would be needed, more species would be "rescued" from extinction using the cage facilities currently available at existing institutions. Doubling generation lengths for callitrichid primates through use of cryopreservation could almost triple the number of species that could be rescued in world zoos. Additionally, long-term cryopreservation would allow for a third population, that of the frozen zoo. Three-way exchange of germ from germ plasm banks to captive and wild populations would increase genetic diversity at reduced risk and expense. Advances in reproductive technology and better understanding of the reproductive physiology of these animal populations are necessary to permit routine application of artificial insemination and embryo transfer using frozen-stored germ plasm. PMID- 1606829 TI - Cryopreservation of poultry sperm: the enigma of glycerol. AB - This review summarizes recent data for cryopreservation of poultry sperm and data establishing the contraceptive effect of glycerol. Successful cryopreservation protocols for bovine sperm are compared to the requirements for rooster sperm, with emphasis on glycerol-induced alterations in avian reproductive systems. It has been shown that molar concentrations of glycerol can affect (a) physical features of the cytoplasm (cytoplasmic organization and viscosity), (b) permeability and stability of the membrane bilayer(s), and (c) noncovalent attachment of proteins to the sperm surface. Perturbing effects of glycerol on sperm metabolism and the essentiality of maintaining bioenergetic balance during the temperature changes associated with any cryopreservation protocol are discussed. Emphasis is placed on the processes in avian reproduction that may be altered by interactions with glycerol. Finally, we discuss the potential value of using available genetic models (lines of roosters differing in the capacity of their sperm to survive a freeze-thaw cycle) to clarify and overcome damage to poultry sperm induced by cryopreservation. PMID- 1606830 TI - Characteristics and kinetics of subzero chilling injury in Drosophila embryos. AB - Drosophila embryos manifest unusually high sensitivity to chilling in that they are killed with increased rapidity by exposure to temperatures between 0 and -25 degrees C in the absence of ice formation. Thus, 50% of 15-h eggs succumb in 35, 4, and 1 h at 0, -9, and -15 degrees C, respectively. The sensitivity becomes substantially greater in embryos at stages of development earlier than 12 h, especially at 3 and 6 h. The killing kinetics at given subzero temperatures between 0 and -25 degrees C are characterized by a shoulder followed by a more-or less linear decrease in survival with time. The lower the temperature, the shorter the shoulder and the faster the postshoulder decline. The rate of both components follows Arrhenius kinetics, i.e., plots of log rate vs 1/absolute temperature are linear, the slopes being proportional to the activation energy. In both cases the activation energy is high and negative; namely, -46.5 kcal/mol for the shoulder length and -24.7 kcal/mol for the postshoulder inactivation. Negative activation energies are unusual, and according to absolute reaction rate theory, they exist only when the entropy of activation is negative, which suggests that the activated state is more ordered. By combining the duration of the shoulder as a function of time and temperature with the rate of postshoulder inactivation, one can compute survival as a function of temperature for embryos cooled at various rates. For those cooled at less than or equal to 1 degree C/min, the computed curve of survival vs temperature agrees closely with observed survivals. But for embryos cooled at approximately 10 degrees C/min, the drop in survival occurs some 7 to 10 degrees above that computed. Embryos exposed to 0 degree C for greater than 5 min undergo conditioning that renders them more resistant to subsequent exposure to lower temperatures, and those cooled at 10 degrees C/min presumably lack sufficient time at 0 degree C to undergo such conditioning; hence the discrepancy between observed and computed survivals. As a test of the possibility that chilling injury is a consequence of the loss of synchrony of coupled reactions involved in embryological development, embryos were rendered anoxic prior to chilling, a treatment that has been shown by Foe and Alberts to reversibly halt development of early stages. Although anoxia somewhat reduced chilling injury in 6-h eggs, it had no effect on 15-h eggs.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1606831 TI - The cryoprotective effect of antifreeze glycopeptides from antarctic fishes. AB - Apparently vitrified cells and tissues often fail to survive, probably from damage from growth of microscopically invisible ice crystals. Special biological antifreezes from some polar fishes have been shown to adsorb to specific faces of ice crystals and inhibit crystal growth. Vitrification in the presence of antifreezes therefore may help enhance postvitrification viability of cells and tissues. We report here that the addition of fish antifreeze glycopeptides (AFGPs) to vitrifying solutions increases post-thaw viability in cultured immature pig oocytes and two-cell stage embryos of mice and pigs after rapid cooling to cryogenic temperatures. The criterion for viability is maturation to metaphase for the oocytes and the ability to develop into the four-cell stage for the pig embryo and the blastocyst stage for the mouse embryo. Without AFGPs, or with addition of antifreeze peptides (AFPs), the particular vitrifying solution and cooling/warming/culturing regime used in this study produced zero viability. In the presence of the AFGPs (40 mg/ml), survival of pig oocytes and embryos was increased to about 25%, and that of mouse embryos to 82%. Dose-response studies for the mouse embryos showed that the protective effect of AFGPs shows saturation kinetics and levels off at 20 mg/ml. The AFGPs appeared to preserve cell membrane structural integrity; however, an intact cell membrane did not always lead to viability. The absence of protective effect by AFPs suggests that protection by the AFGPs is unrelated to their common antifreeze property, i.e., inhibition of ice crystal growth, but probably results from interaction with and stabilization of the cell membranes unique to the AFGPs. PMID- 1606832 TI - The cryopreservation of liposomes. 2. Effect of particle size on crystallization behavior and marker retention. AB - Liposome dispersions (bilayer composition Phospholipon 100H/dicetylphosphate (molar ratio 10:1) dispersed in 10 mM Tris buffer) are frozen in a differential scanning calorimeter. In the cooling curves of the dispersions a heat-flow below 40 degrees C is observed. This heat-flow is due to the crystallization of maximally supercooled water. Evidence is provided that at this temperature, defined as the homogeneous nucleation temperature, part or all encapsulated water in the liposomes crystallizes. At a cooling rate of 10 degrees C/min only for small liposomes with particle sizes below approximately 0.2 micron the internal volume crystallizes at the homogeneous nucleation temperature. After a freezing/thawing cycle of the liposomal dispersions retention of the water soluble marker carboxyfluorescein (CF) was significantly better if crystallization of the encapsulated volume occurred at the homogeneous nucleation temperature. Up to 55% retention of CF in dispersions with mean vesicle sizes below 0.2 micron was found after storage for 45 min at -50 or -75 degrees C. Only relatively small particle size alterations were found in comparison with the original mean particle sizes after a freezing/thawing cycle with storage for 45 min at -50 or -75 degrees C. Independent of particle size, dispersions stored for 45 min at -25 degrees C showed low CF retention (less than 10%) after thawing. For most of the liposome dispersions stored at -25 degrees C, large particle size alterations compared to the original particle sizes were observed after a freezing/thawing cycle. PMID- 1606833 TI - Freezing preservation of the mammalian cardiac explant. II. Comparing the protective effect of glycerol and polyethylene glycol. AB - We compared the cryoprotective ability of glycerol and polyethylene glycol (PEG) during freezing. Isolated rat hearts were flushed with one of three cardioplegic solutions (CP-14, CP-15, and CP-16), frozen at -1.4 degrees C, and reperfused after thawing to assess function. After 3 h freezing, cardiac output (CO) in CP 14-flushed hearts recovered to 58.1% of control. CP-16 (CP-14 with 5% PEG) improved CO to 77.5%. Five hours of freezing abolished recovery in CP-14 hearts, but CP-15 (CP-14 with 50 mM glycerol) and CP-16 hearts produced 40.0 and 49.0% CO, respectively. With 6 h freezing, CP-15 hearts did not recover, whereas CP-16 hearts recovered 37.5% CO. In CP-14 hearts frozen for 3 h, 37.4% of the tissue water was ice that increased to 44.7% with 5 h freezing. CP-15 and CP-16 hearts had 34.4 and 30.9% tissue ice, respectively, after 5 h freezing. Tissue water contents in CP-14 and CP-15 hearts (3.83 to 3.96 g H2O/g dry) were 14 to 24% higher than that in CP-16 hearts. Six hours of freezing elevated AMP and ADP contents and reduced ATP levels in CP-15 and CP-16 hearts. Total adenine nucleotide (TAN) content of CP-15 hearts was 72% of control, while that of CP-16 hearts was normal. In conclusion, both glycerol and PEG offered cryoprotection by reducing tissue ice formation. PEG was superior by reducing tissue ice content further via dehydration and by better preserving TAN content. PMID- 1606834 TI - Predictive water loss curves for ram spermatozoa during cryopreservation: comparison with experimental observations. AB - Calculated curves predicting intracellular water loss during cryopreservation at different cooling rates were calculated from published equations. To compute these curves, basic cell parameters specific to ram spermatozoa were measured, i.e., the total surface area (139 microns2), the hydraulic conductivity (0.222 micron3/micron2.atm-1.min-1), and its temperature dependence (0.045/degree C). Cell surface area was derived from measurements of physical dimensions. Hydraulic conductivity was calculated from measurements of the critical medium hypotonicity on exposure of sperm to various hypotonic solutions and the time taken for membrane rupture in sperm exposed to distilled water (spermolysis time). The temperature dependence of the water permeability was derived from measurements of spermolysis time at various temperatures above zero. Several discrepancies were noted between the resulting calculated curves and experimental observations made on the effects of cooling rate on sperm cell survival. These could be due to errors in the estimates of the basic parameters, or to false assumptions in the basic equations used to compute the curves, e.g., the validity of the Boyle-van't Hoff relationship. Nevertheless, this study represents a first attempt to predict intracellular water loss from ram sperm during cooling and may provide a novel approach for the interpretation of the many empirical studies carried out to investigate optimal conditions for the cryopreservation of sperm. PMID- 1606835 TI - Altered lectin binding sites in keratoconus corneas. AB - We investigated the glycoconjugates in frozen sections of keratoconus corneas, using a panel of 12 biotin- or fluorescein isothiocyanate-labeled lectins. No differences between the lectin binding sites of the epithelium, endothelium and Descemet's membrane of normal and keratoconus corneas could be observed. However, in contrast to normal corneas, intense staining with peanut agglutinin (PNA) could be detected at breaks in Bowman's layer, in scar tissue and in the adjacent stroma. Furthermore, in the majority of cases binding sites for Phaseolus vulgaris erythroagglutinin (PHA-E) and increased staining with Ricinus communis agglutinin I (RCA-I) and Lens culinaris agglutinin (LCA) could also be detected in ruptures in Bowman's layer and in scar tissue. These data suggest that the scarred regions of the anterior stroma in keratoconus corneas may contain oligosaccharides with terminal D-galactose (beta 1-3)-D-N-acetylgalactosamine disaccharides (recognized by PNA), increased amounts of glycoconjugates with terminal beta-galactose residues (recognized by RCA-I), increased amounts of glycoconjugates with glucose/mannose residues (recognized by LCA), and finally, biantennary complex-type glycopeptides containing two outer galactose residues and a residue of N-acetylglucosamine (recognized by PHA-E). Since corneal scars due to causes other than keratoconus revealed lectin binding sites (particularly for PNA and to a lesser extent also for PHA-E, LCA and RCA-I) similar to those seen in scar tissue of keratoconus corneas, we conclude that it is mainly scar formation that may be responsible for the altered lectin binding sites in keratoconus. PMID- 1606836 TI - Hyaluronic acid--syneretic glycosaminoglycan. AB - Hyaluronic acid from different sources, umbilical cord, vitreous, rooster comb and streptococcus, all exhibit a unique hydration behavior. Each hyaluronic acid and each different salt form has a maximum non-freezable water content at a set concentration beyond which the bound (non-freezable) water decreases. This type of behavior indicates a syneretic process simply due to concentration alone. PMID- 1606837 TI - Assignment of the lens intrinsic membrane protein MP19 structural gene to human chromosome 19. AB - We have isolated and characterized a bovine cDNA clone encoding the bovine lens intrinsic membrane protein, MP19. This cDNA was used as a probe to analyze a panel of Southern blots of human-Chinese hamster somatic cell hybrid DNAs to assign the gene coding for MP19 to its human chromosome. Control human and Chinese hamster DNAs displayed a distinct EcoR1 restriction fragment pattern when hybridized with the bovine MP19 cDNA. When somatic cell hybrid DNAs were restricted with Eco R1 and Southern blots hybridized with the bovine MP19 cDNA, the characteristic human restriction pattern was observed only when human chromosome 19 was present in the hybrid panel. This assignment was confirmed using a human chromosome 19-specific genomic library. A clone from this human chromosome 19-specific library was identified and further characterized. This clone contained a 7.9 kilobase fragment that contained identical DNA sequences with that of the authentic bovine MP19 cDNA, and with a separate human genomic clone containing the MP19 gene. PMID- 1606838 TI - Retinoblastoma: messenger RNA for interphotoreceptor retinoid binding protein. AB - Surgically excised retinoblastomas from 14 patients (age range nine months to two years) were assessed by immunocytochemistry for the expression of photoreceptor specific proteins and neuronal and glial cell markers. Adjacent tissues were examined for messenger RNA expression of interphotoreceptor retinoid-binding protein (IRBP) using Northern blots. For immunocytochemical stains (ABC method), monoclonal and polyclonal antibodies included S-Ag, rhodopsin, neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP), IRBP, neural adhesion molecule (N-CAM), and rod and cone specific transducin (TR alpha and TC alpha). Histopathology revealed mostly poorly differentiated tumors with necrosis and lack of Flexner-Wintersteiner rosettes. Immunocytochemical staining showed focal IRBP expression in one of the tumors and S-antigen in two cases. Immunoreactivity with rhodopsin was negative. N-CAM, a neural adhesive protein which appears to be involved in the regulation of adhesive interaction during neuronal differentiation, was positive except in two cases. All tumors showed immunoreactivity with NSE, whereas GFAP staining was limited to the perivascular glial tissue confirming the essential neuronal nature of retinoblastoma cells. TC alpha was detected in all tumors and TR alpha in one case. Messenger RNA for IRBP was detected in tumors in which IRBP immunoreactivity could not be detected. PMID- 1606839 TI - Purine salvage as a metabolite and energy saving mechanism in the ocular lens. AB - The ocular lens is an organ which depends mainly on anaerobic processes to obtain the metabolic energy required for the maintenance of its physiological functions. In these circumstances, the purine salvage pathway enzymes, by using preformed purine rings, and allowing the utilization of the activated ribose moiety of nucleosides, might be of relevance as an energy saving device. In this paper we show that the calf lens possesses many enzymes of the purine salvage pathway, with a particularly high specific activity of purine nucleoside phosphorylase (EC 2.4.2.1), and that the isolated lens epithelium can actively convert adenine and adenosine into adenine nucleotides. In addition, as in bacteria and red blood cells, inosine and adenosine in the lens, acting as ribose donors, exert a profound effect on the process of adenine conversion into ATP. PMID- 1606841 TI - Ocular hypotensive activity of the adenosine agonist (R)-phenylisopropyladenosine in rabbits. AB - Adenosine A1 agonists have been shown to induce a variety of pharmacological effects. In New Zealand White rabbits, the topical administration of 500 micrograms of the relatively selective adenosine A1 receptor agonist R(-) phenylisopropyladenosine (R-PIA) produced a biphasic response in IOP in the ipsilateral eye: an initial ocular hypertension (3.5 +/- 1.4 mm of Hg) at 0.5 hour, followed by significant reduction in IOP (5 to 8 mm of Hg) from 2 to 6 hours postadministration. The IOP response to 50 and 165 micrograms of R-PIA demonstrated that the ocular hypotensive response to R-PIA was dose-related; however, no initial hypertension was observed at these lower doses. The ocular response to R-PIA was primarily unilateral with only a small reduction in contralateral IOP at 1 hour observed in animals treated with 500 micrograms. No significant change in pupil diameter was observed with any dose of R-PIA. Pretreatment with the adenosine antagonist CPT (10 mg/kg; i.p.) significantly inhibited the ocular hypotensive response to R-PIA. However, pretreatment with the cyclooxygenase inhibitor indomethacin (50 mg/kg; i.p.) did not alter the change in IOP induced by R-PIA. The administration of R-PIA once a day for five days demonstrated that tolerance does not develop in rabbits with repeated administration. These data demonstrate that the adenosine A1 agonist R-PIA can lower IOP. The unilateral nature and the inhibition by CPT supports the idea that this response is mediated by adenosine receptors located in the eye.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606840 TI - HLA DQA tissue typing of cadaveric eye bank donor material with polymerase chain reaction. AB - It has been suggested that the provision of HLA matched tissue for corneal transplantation would be beneficial for graft survival especially in high risk patients. In this study we report the application of a polymerase chain reaction (PCR) based tissue typing procedure to type cadaveric donor material. Using beta globin gene amplification as a test system we found that cornea, corneal rim, conjunctiva, sclera, rectus muscle, optic nerve and neural retina were all suitable for PCR amplification but DNA extracted from pigment epithelial cells and from the iris could not be amplified. HLA DQA typing results of 9 samples identified 5 alleles and 7 genotypes. In two cases the antigens detected by serology reflected the alleles detected by PCR. In a third case in which the class II serological typing was inconclusive we detected two DQA alleles by PCR. These alleles were consistent with those which would be predicted to be present on the basis of known linkage disequilibrium between HLA-Cw, B, DR and DQ. In this study we have shown that PCR based tissue typing is more sensitive and gives more detailed typing results than serology and would be suitable to type cadaveric donor material on a routine basis. PMID- 1606842 TI - Cardiac effects of different eyedrop preparations of timolol in rabbits. AB - Coadministration of phenylephrine and increasing solution viscosity can decrease systemic timolol absorption after eyedrop application. In this study, changes in the heart rate of rabbits after non-viscous (1 cP) and viscous timolol phenylephrine (330 cP) solution were compared with those after control timolol eyedrops. The resting heart rate of rabbits was not influenced by control timolol eyedrops (0.6 mg/ml, 25 microliters in both eyes). In contrast, control timolol eyedrops antagonized greatly isoproterenol-induced tachycardia for 120 min. Timolol (0.6 mg/ml)-phenylephrine (0.8 mg/ml) eyedrops (25 microliters in both eyes) antagonized the chronotropic effect of isoproterenol less than control timolol eyedrops for the first 10 min. Compared to control timolol eyedrops, administration of viscous timolol (0.3 mg/ml)-phenylephrine (0.8 mg/ml) solution (25 microliters in both eyes) lowered systemic beta-blocking activity of timolol for 120 min. Previously we have shown that compared to non-viscous (1 cP) timolol (5.0 mg/ml) eyedrop (25 microliters), viscous (330 cP) timolol (2.5 mg/ml) phenylephrine (0.8 mg/ml) solution (25 microliters) results in equal or increased timolol concentrations in the ocular tissues. All three timolol eyedrops antagonized the isoproterenol-induced tachycardia more than buffer solution but the onset of significant beta-blocking effect induced by eyedrops varied from 3 min (control eyedrop) to 40 min (viscous eyedrop). Our results indicate that possible cardiac effects of ophthalmic timolol can be diminished by phenylephrine coadministration and increased solution viscosity. PMID- 1606843 TI - Carbonic anhydrase III is expressed in bovine lens. AB - A highly basic protein isolated from bovine lens has been shown to be carbonic anhydrase III by immunological and peptide sequencing techniques. This is the first demonstration of the presence of this isoenzyme, which is primarily found in skeletal muscle, in the lens or other ocular tissues. The physiological function of this enzyme in the lens is unknown. PMID- 1606844 TI - Current therapy for supraventricular tachycardia. PMID- 1606845 TI - Outpatient physiologic testing and surgical management of foregut motility disorders. PMID- 1606847 TI - The role of after-school programs in the lives of inner-city children: a study of the "urban youth network". AB - A study of a network of agency centers located in eight of Chicago's most deprived neighborhoods reveals a great deal about inner-city children and the difficulties of reaching them and holding their attendance. It also points up sharply the funding and staffing necessary to enable the centers to realize their potential for services to these children. PMID- 1606846 TI - Serving the urban poor: a study of child welfare preventive services. AB - This summary, for journal publication, of a study whose full details are being published in book form, brings the welfare field up-to-date on what began as a precedent-setting agency. The Lower East Side Family Union, in New York City, has provided many years of service, and has justifiably drawn national attention from its inception, when prevention was more talked about than funded. The lessons to be drawn from its work and the example it has set grow more timely every year. PMID- 1606848 TI - Male victims of sexual abuse: a case review within a child protective team. AB - A retrospective review of 77 cases of sexual abuse of boys seen for assessment by a multidisciplinary child protection team in Florida collected data on age at time of referral, findings of medical examinations, sex of offender, relationship of offender to child, and type of abuse. The history of abuse was categorized as (1) short-term, (2) intermediate, or (3) long-term. An examination was made of the relationship of length of abuse to (a) suicidal ideation reported by or of the boy, (b) threats by the offender directed at the victim, and (c) a history of recapitulation of sexual abuse. The findings of the review, as reported here, further the momentum of research on male victims of sexual abuse, a category of abuse that is seeing an increasing rate of referrals. PMID- 1606849 TI - The Maternal Characteristics Scale: a cross validation. AB - A device for organizing practitioners' observations, the Maternal Characteristics Scale has successfully identified traits distinguishing samples of Caucasian neglectful mothers from nonneglectful. This cross-validation tested the scale with new and more diverse samples of both mothers and practitioners. Relatedness, impulse control, confidence, and verbal accessibility were again found to be associated with vulnerability to becoming neglectful. The scale appears to be a promising diagnostic and prognostic tool in the prevention and treatment of child neglect. PMID- 1606850 TI - [The surgeon in conflict with increasing specialization. Opening speech of the chairman of the 148th Congress of the Society of North German Surgeons 5 December 1991 in Hamburg]. PMID- 1606851 TI - [Limits of the possible from the ethical viewpoint]. PMID- 1606852 TI - [Status and problems of intensive care]. PMID- 1606853 TI - [Economics as the limiting factor in intensive therapy in advanced age?]. PMID- 1606854 TI - [The beginnings of stomach surgery in the Middle Ages. Florian Matthis--wound physician and surgeon of Brandenburg/H]. PMID- 1606855 TI - [What is confirmed in chemo- and immunotherapy of solid tumors. Standard protocols, studies and new developments]. AB - Reviewing the treatment perspectives with chemo- and immunotherapy in carcinomas and sarcomas to be treated by general or orthopedic surgeons, the following indications are regarded as recommendable: Adjuvant chemotherapy in breast cancer, neoadjuvant chemotherapy with radiation in anal carcinoma and neoadjuvant/adjuvant chemotherapy of high-grade malignant osteosarcoma. Isolation perfusion currently is the treatment of choice in melanoma metastasis limited to an extremity. With several indications, recent developments have produced promising results that should be urgently confirmed in appropriate studies. Therefore the following studies have a high priority: Neoadjuvant chemotherapy in esophageal carcinoma and in locally advanced breast and stomach cancer, adjuvant chemoimmunotherapy in colon carcinoma UICC III and chemoradiation in rectal carcinoma UICC II and III, systemic chemotherapy of metastasized stomach-, colorectal-, breast cancer and sarcomas. Isolated non-resectable liver metastases of colorectal origin and hepatocellular carcinoma should be included in studies evaluating the treatment advantage of regional chemotherapy. Those malignant "surgical" tumors not listed above should receive chemotherapy within experimental studies, after consideration of individual risk factors, or no chemotherapy. Immunotherapy with its various modalities is still in the experimental stage. PMID- 1606857 TI - [Diabetic gangrene in peripheral vascular occlusion. Saving the extremity by popliteo-pedal venous bypass]. AB - 23 patients with diabetic gangrene and complete occlusion of all 3 tibial arteries were treated by 26 popliteopedal vein bypass grafts. All 6 early graft failures resulted in major amputations. The cumulative graft patency rate was 76% after 6 years. One patient needed lower-leg amputation despite a functioning graft. All other limbs were saved (mean follow-up period: 24.8 months). It is concluded that despite a palpable popliteal pulse an angiographic examination should be performed, when the infectious lesion cannot be controlled by local treatment and pedal pulses are absent. PMID- 1606856 TI - [Osseous leiomyoma--a first-time description]. AB - In a 54-year old housewife presenting with left hip pain due to a circumscribed intraosseous lesion of the femoral neck, histological assessment following resection showed a benign intraosseous leiomyoma. Years ago a diagnosis of disseminated peritoneal leiomyomatosis had been made. PMID- 1606858 TI - [Slit drainage--progress in drainage treatment after herniotomy]. AB - In a prospective randomized study was conducted on 80 patients undergoing elective hernia repair to assess whether a new slit-suction drainage is less painful than a Redon-suction drainage. Main endpoint of the study was the traction power in order to remove the drain. Other endpoints were pain at the time of removal of the drain and the effectiveness to draw off secretion. To remove redon drain the average traction power was 226 pond and to remove slit drain the average traction power was only 25 pond. The difference was significant (p less than 0.01). At the time of removal patients with slit drain rarely complained about pain (p less than 0.01). On contrary, patients with Redon drain always complained about pain. Clotting were seldom shown in slit drains and were frequently shown in redon drains. Both slit drains and redon drains were effective to drain secretion. As the new slit drain was more comfortable for patients following hernia repair slit drain should always be used as subcutaneous suction drainage. PMID- 1606859 TI - [What suction drainage is optimal for drainage of wound secretion? A clinico experimental study exemplified by the knee joint]. AB - In a randomized clinical study on 40 intraarticular knee joint drainages the effect of a high vacuum, middle vacuum, low vacuum and suction free drainages were examined. The maximum of the volume that was drained had been in the group of the suction free drainages. Drains with a long period of suction had a minimum of evaluated ultrasonographic effusion in the knee joint. The group with high vacuum was obviously not as long as open as in the other groups. Thrombi in the drainages could be found in every group. This refers to the observation that the finding of adherent thrombi is related to the material the drain is made of. Adherent thrombi decrease the possibility of secretion, not adherent thrombi do not decrease suction volume. Referring to these results it is obvious that not the high-vacuum drainage is the matter of choice for intraarticular drains. The suction-free drainages or drains with reduced vacuum have more advantages in respect to simple, secure and fast implantation and handling. PMID- 1606861 TI - [Blast injury of the face and its treatment]. PMID- 1606860 TI - [The Thibierge-Weissenbach syndrome. Tumorous soft tissue calcifications within the scope of scleroderma]. PMID- 1606862 TI - [Spontaneous closure of gastrointestinal perforation]. PMID- 1606863 TI - [The beginnings of stomach surgery in the Middle Ages. Florian Matthis--wound physician and surgeon of Brandenburg/H]. PMID- 1606864 TI - [Inhibitory effects of balsam pear on the mutagenic activity of cyclophosphamide in vivo]. AB - Inhibitory effects of balsam pear on the mutagenic activity of cyclophosphamide were studied in the cells of bone marrow of mouse in vivo. It was found that balsam pear juice itself showed no effect on the incidence of sister chromatid exchanges (SCE) and of micronuclei (MN) on the cells of bone marrow. But balsam pear juice reduced the incidence of SCE (from 29.1 times/cell to 13.27-28.38 times/cell) and MN (from 60.0% to 27.0%-50.0%) induced by cyclophosphamide respectively. The inhibitory effects showed a dose-dependent relation, which was statistically significant. PMID- 1606866 TI - [Keshan disease and the selenium content of grains in Yunnan province]. AB - The selenium content of 518 specimens of rice, wheat, maize, soybean and highland barley growing both in Keshan disease area and other places in Yunnan Province, was determined and it was found that the average selenium content of the grains in the Keshan disease area was lower than that in the other places. The selenium content of rice especially was much lower than that of wheat and soybean. The relationship of Keshan disease to the low selenium content of grains, especially rice, the most eaten grain by people in the disease area, seemed clearly established in Yunnan province as well. PMID- 1606865 TI - [Fungi N-nitrosamines and mutagens in the extract of the sour corn-soybean cakes from high incidence area of stomach cancer]. AB - Sour corn-soybean cake is the main food of the inhabitants in high incidence area of stomach cancer in Linqu county Shandong province. In the extract of the sour corn-soybean cakes, twelve mycotoxin-producing fungi and 3 N-nitrosamines (NDMA, NDEA, NMEA) were detected and the finding rates of the fungi and the N nitrosamines were 93.3% and 92.3%, respectively; the concentration of NDMA was 0.4-3.8 ng/ml, NDEA 0.2-8.1 ng/ml, and NMEA 0.3-1.4 ng/ml. The positivity rate of the Ames test (most positive materials were direct mutagens) was 44.12%. The experimental results showed that the extract of the sour corn-soybean cakes containing carcinogenic and mutagenic subjects could have some causal relationship with the incidence of stomach cancer. PMID- 1606867 TI - [Research of the physicochemical properties of hair in endemic arsenism area]. AB - The paper reports the results of research of hair in the endemic arsenism area where water with arsenic content is 0.58 mg/L in Kuitun district, Xinjiang. In the area of endemic arsenism, the content of hair arsenic with arsenism patients is higher than that of subjects without arsenism. Hair arsenic content among residents was also higher than those of control areas. The stretch and relative strength of hair of subjects living in the area of endemic arsenism were lower than those of the areas of control. The ultrastructure of hair surface has obvious pathologic changes by scanning electron microscope examination. By using a hygienic standard (the arsenic content of water being 0.03 mg/L) to improve the drinking water for two years, the content of hair arsenic has reduced, approaching 95% upper confidence limit for normal hair (1.5 micrograms/g). The stretch and relative strength of hair have distinctly increased. The ultrastructure of hair surface has returned to near normal. The results of our investigation show that we should pay attention to the latent harm to residents in the high-arsenic-content area. The authors consider that hair arsenic content, stretch and relative strength of hair are sensitive and objective indexes to monitor the effects of improving water quality in area of endemic arsenism. PMID- 1606868 TI - [The effects of chlorine disinfection on the resistance of E. coli in water]. AB - Under defined conditions E. coli were subjected to repeated chlorine disinfections 10 times. The survival E. coli at 30 s (A10), and the survival E. coli at 10 min (B10) had no difference in resistance to chlorine to their original strain (A0). However, the compound E. coli (C10) survived at various contact time showed an increased resistance than their original strain (A10), the degree of increased resistance varying with different conditions of disinfection. E. coli C1(0) lost its increased resistance after it has been passaged 10 times on nutrient agar. PMID- 1606869 TI - [Related factors for the development of delayed encephalopathy following acute carbon monoxide poisoning]. AB - Two hundred and twenty three cases of acute carbon monoxide poisoning were observed during acute stage and followed-up subsequently for three months. Through single factor and multiple factors analyses, six out of 97 observed factors were demonstrated as risk factors for the development of delayed encephalopathy, namely, elderliness, mental work, previously with hypertension, coma lasting for 2-3 days, long standing dizziness and fatigue after regaining consciousness and mental stimulation during recovery. Based on these factors, a regression equation for predicting the probability of developing delayed encephalopathy in individual patient with acute carbon monoxide poisoning has been established In order to minimize the development of delayed encephalopathy, it is advisable to keep the patients of acute carbon monoxide poisoning with above mentioned related factors under constant monitoring and surveillance. PMID- 1606870 TI - [Microelement-molybdenum and its use for the treatment of children's fluorine stained teeth]. AB - This paper is a study of the effects of molybdenum on the experimental fluorine poisoning in rats and on sodium molybdate treatment of the F-stain teeth in children. The experimental results show that the high-F and Mo feed animal, the excretion of urine-F was more than high-F, the F-content of teeth was reduced, the pathological change of skeletal tissue was relatively little, when sodium molybdate was used to treat children with fluorosis teeth for 3 months, the hair F would reduce, whereas the hair-Mo increase the immune function would rise--the PHA skin test positive rate raised from effect 33.3% to 69.2%. It is suggested that Mo can interfere with the F-poisoning effect and that Mo may well be used as z worth medicine for the prevention and control of this illness. PMID- 1606871 TI - [Diseases caused by non-O1 vibrio cholerae contaminated food]. PMID- 1606872 TI - [Exploration of the relation between hepatitis B virus and liver cancer]. PMID- 1606873 TI - [Effect of Chinese tea extract on the immune function of mice bearing tumor and their antitumor activity]. AB - The dynamic changes of cellular immune function and antitumor effect of GTE (green tea extract) in the BALB/c mice bearing EAC, HAC and S-180 tumor were investigated. Results showed that intraperitoneal injection GTE daily dose of 80mg/kg stimulate the proliferation of T-Lymphocyte S-180 tumor bearing mice, the 125-IudR incorporation value (cpm) of control group was 932 and that of GTE treated group increased to 2988. The Natural Killer cell's activity (cpm) of treated group was raised from 10.7% of control group to 41%. Daily dose 50mg/kg inhibited the EAC, HAC and the life span of GTE mice bearing EAC ascites tumor prolonged 128%. The GTE were effective on growth activity against mouse Ehrlich tumor at a dose of 500mg/kg by oral administration (P less than 0.05), the inhibition ratio being about 32%. The authors suggested the mechanism of antitumor effects of GTE possible included both cellular immune function and the inhibition of tumor growth. PMID- 1606874 TI - [Identification of toxigenic mould in soft drink causing food poisoning]. AB - In a soft drink caused food poisoning, white floccus was found and mould count was 6.0 x 10(2) CFU/ml. The Mycoflora was made of only one kind of mould which was identified as Penicillium janthinellum Biourge. This isolate can grow under anaerobic condition. The culture liquid of the isolate was fed to mice orally for toxicity test, which made the mice lose weight. An extract of the culture liquid was tested in weaned mice inaberitoneally for toxicity and all mice died in 24h. The toxic symptoms were tic, sway and paralysis of right rear-leg. Gross anatomy changes were gastrectosis, flatulence and intestinal edema. The conclusion is: the P. janthinellum isolate from the soft drink was the toxigenic mould. PMID- 1606875 TI - The role of host management in tick population changes on Rusinga Island, Kenya. AB - Contrary to patterns described elsewhere, tick numbers on Rusinga Island cattle drop markedly after the onset of the rainy season. One possible explanation is that this is related to seasonal differences in host behaviour, since cattle grazing on the island are restricted during the crop-growing season (the rainy season) and free grazing afterwards. In a field experiment, cattle were divided into two groups, free grazing and restricted, for 2 months each during the rainy season and during the dry season, and the number of ticks infesting each group was compared. In both seasons, the free-grazing group carried more ticks than the restricted group. Not only did the restricted group come into less contact with ticks, they were also exposed to tick-predating chickens for longer periods each day than the free-grazing group. Management practices that affect host behaviour should, therefore, be taken into consideration in tick population studies. PMID- 1606876 TI - Electron microscopy: the neglected tool of cytopathology. PMID- 1606877 TI - The 1990s--interface of cytopathology and new technology. AB - In physical chemistry, the most unique and dramatic reactions occur at the interface between different phases of matter. An analogy can be drawn between this observation and the interface that currently exists between the traditional practice of cytopathology and the technologies discussed in this editorial. It is natural to be excited about new technologies. They offer the potential to improve our diagnostic ability, to save time, and to expand the range of cytopathology services. Our enthusiasm for new technology should be tempered by the inherent appeal of cytopathology--its relative simplicity. Cytologic diagnoses are possible with a glass slide, extracts of tree bark, and a well-trained observer. This can be rapid and tremendously cost effective, not only identifying the type of abnormality, but often providing prognostic information. New technology, while offering additional information, may not be cost effective, or may not offer more information than is available by traditional methods. Whether or not to accept new technologies is the choice of cytotechnologists and cytopathologists. It is the goal of the Editorial Board of Diagnostic Cytopathology that this be a well informed choice. The current and coming issues of Diagnostic Cytopathology will describe technological advances in the Focus on Technology section of the journal. We trust that you will find this information useful in your evaluation of new technology. PMID- 1606878 TI - AgNOR counts are useful in cervical smears. AB - Because they present marked cellular changes, the cytological appearances of epithelial repair may be confused with those of cancer. To see whether the Ag-NOR staining technique for nucleolar organizer regions would be useful to distinguish benign proliferative reactions (squamous metaplasia and repair) from cervical intra-epithelial neoplasia (CIN I, CIN II, and CIN III), we studied a series of cervical smears. The smears, previously stained with the Papanicolaou technique, were destained and restained with Ag-NOR silver. Significantly different (P less than 0.05) Ag-NOR counts were found in squamous metaplasia, epithelial repair, and various degrees of CIN. The Ag-NOR technique appears useful in the diagnosis of cervical cytology and particularly in cases with marked cellular change, which could be confused with neoplasia. PMID- 1606879 TI - Superficial and deep-seated tuberculous lesions: fine-needle aspiration cytology diagnosis of 574 cases. AB - Over a period of 2 yr (1987-1988), FNA smears in 574 cases were found to have cytologic features suggestive of or consistent with tuberculous lesions. The age of the patients ranged from 6 mo to 75 ye, with a median of 24 yr. The male to female ratio was 273:301. Sites of FNA were superficial lymph nodes (SLN) in 440 (76.7 percent) cases, superficial extranodal sites (SENS) in 50 (8.7 percent), both SLN and SENS in 7 (1.2%), the thoracic cavity in 16 (2.8%), and the abdominal cavity in 61 (10.6%). Cytologic features were described under 3 major cytologic patterns, i.e., type I: epithelioid granuloma without necrosis, type II: epithelioid granuloma with necrosis, type III: necrosis without epithelioid granuloma. Type I, II, and III reactions were observed in 181 (31.5%), 183 (31.9%), and 210 (36.6%) cases, respectively. The overall AFB positivity was 30.8%. The AFB positivities for type I, II, and III cytologic reactions were 5.4%, 32.0%, and 48.5%, respectively. The AFB positivity was low (less than 30.0%) in swellings of the body surface (23.8%) and abdominal organs (18.9%). High positivity (greater than 60.0%) was observed in lesions of the thorax (63.6%) and thyroid (62.5%). PMID- 1606880 TI - Urothelial toxicity following conditioning therapy in bone marrow transplantation and bladder cancer: morphologic and morphometric comparison by exfoliative urinary cytology. AB - Since cyclophosphamide and busulphan used for therapy of bone marrow transplantation (BMT) can cause urothelial cell changes similar to those found in bladder cancer, comparative morphologic and morphometric urinary cytologic research was carried out, examining 812 urine samples taken from 121 patients undergoing BMT and 60 urine samples from 20 patients with bladder cancer. The morphological results showed some differences in the characteristics of the urinary sediment in urothelial toxicity caused by conditioning therapy in BMT and in bladder cancer; among these were background, cellularity, leukocytes, urothelial cell arrangement, cell shape and size, vacuolization, mitosis, and nucleoli. A comparative morphometric study was also carried out, showing differences regarding cell area, nuclear area and perimeter, and N/C ratio, especially between well-differentiated bladder cancer and urothelial toxicity. PMID- 1606881 TI - Fine-needle aspiration cytology of spindle cell neoplasms of the adrenal gland. AB - Three spindle cell neoplasms were encountered in a series of 46 FNA of the adrenal performed between 1984 and 1991. These neoplasms included a recurrent undifferentiated adrenal cortical carcinoma (ACC) with a predominant spindle cell pattern, a pheochromocytoma (PC), and a metastatic desmoplastic malignant melanoma (DMM). Cytologically, the ACC was characterized by the presence of numerous microtissue fragments composed of spindle-shaped malignant cells with oval to spindle-shaped nuclei, one or more nucleoli, and bipolar cytoplasmic processes. In some areas the tumor cells were dissected by vascular channels. The background contained abundant metachromatic stroma as well as individually scattered tumor cells. The PC was composed predominantly of loosely cohesive spindle-shaped cells along with more polygonal shaped cells with delicate faintly staining granular cytoplasm. The tumor cells exhibited mild anisonucleosis. The tumor fragments were well vascularized by arborizing delicate capillary channels. The DMM was composed of microtissue fragments, interlacing fascicles and loose aggregates of spindle-shaped malignant cells with hyperchromatic nuclei, small nucleoli, and an absence of cytoplasmic pigment. In each case ancillary studies including immunocytochemistry and electron microscopy (EM) were helpful in the differential diagnosis. The ACC was negative for cytokeratins, neuron-specific enolase (NSE), and muscle-specific actin (HHF), but displayed strong positivity for vimentin as well as characteristic whorls of smooth endoplasmic reticulum by EM. The PC was positive for NSE and chromogranin with no EM performed. The DMM stained for S-100 and vimentin but was negative for HMB-45, cytokeratin, and HHF. EM examination revealed rare atypical premelanosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606882 TI - Aspiration biopsy of granulosa-cell tumor of the ovary: cytologic findings and differential diagnosis. AB - Fine-needle aspirates from four histologically confirmed adult granulosa-cell tumors of the ovary revealed irregular sheets, loose aggregates or tight clusters of small tumor cells with round or oval nuclei and scant cytoplasm. Nuclear grooves and indentations were noted in a small number of cells in two cases. Tumor cells arranged in follicular pattern mimicking Call-Exner bodies were not identified in all cases. A cytologic differential diagnosis of "small-cell" tumors of the ovary is briefly discussed. PMID- 1606883 TI - Fine-needle aspiration biopsy of pediatric neoplasms: correlation between electron microscopy and immunocytochemistry in diagnosis and classification. AB - A series of fine-needle aspiration biopsies performed in 635 children were reviewed. The diagnoses rendered in these patients included malignant lymphoma in 139 (21.9%); Hodgkin's disease, 25 (3.9%); neuroblastoma, 58 (9.1%); Wilms' Tumor, 37 (5.8%); Ewing's sarcoma, 32 (5.0%); rhabdomyosarcoma, 25 (3.9%); retinoblastoma, 22 (3.5%); leukemia infiltrate, 33 (5.2%); and miscellaneous tumors, 52 (8.2%). In 171 patients (26.9%), the biopsy was nondiagnostic. The cytomorphological characteristics of these lesions are briefly described and illustrated. Salient morphological features are further correlated with histological and ultrastructural appearances. Immunocytochemical patterns of these tumors are also discussed briefly. PMID- 1606884 TI - Scanning electron microscopy of body fluids. AB - Scanning Electron Microscopic (SEM) examination of body fluid specimens submitted for cytopathological diagnosis is technically easy and can be accomplished within hours. Specimens refrigerated for as long as 72 hr show no significant structural alterations that would interfere with recognition of diagnostically significant cells. SEM is particularly well suited for these specimens because the cells are free floating, and even cells in clusters have "natural" surfaces. Clinical uses of SEM on body fluids include the identification of ambiguous cells, distinction of reactive (benign) mesothelial cells from metastatic adenocarcinoma, and distinction of lymphoid cells from small cell carcinoma of the lung. In addition, SEM of these fluids assists cytologists to better understand the cellular features and associations seen in the light microscope. Ultrastructural analysis can be an important component of the Quality Assurance Plan for those cytodiagnostic laboratories that have access to an electron microscopy facility. PMID- 1606885 TI - Electron microscopy of fine-needle aspiration biopsies of the mediastinum. AB - Twenty cases of fine-needle aspiration (FNA) biopsy of mediastinal tumors with ultrastructural studies of the aspirated material were reviewed. The cases were classified according to the cytologic and ultrastructural diagnosis. A specimen insufficient for ultrastructural study was obtained in five cases (25%). Refinement of the cytologic diagnosis was made in three cases (15%) and good correlation between the initial cytologic impression and the ultrastructural studies was seen in the remaining cases (60%). Comparison of different sites of FNA biopsy revealed a higher rate of ultrastructural examination in the cases involving the mediastinum. Illustrative cases of the use of electron microscopy in FNA biopsies of mediastinal tumors are presented. PMID- 1606886 TI - Electron microscopy of fine-needle aspiration biopsy specimens: a brief review. AB - The cellular sample obtained by fine-needle aspiration biopsy is usually small and therefore requires extreme care during processing for electron microscopy. The most significant technical problem is due to contamination of the sample by red blood cells, which tend to dilute the samples. Red blood cells in these samples may be removed prior to processing by either using Bovine serum albumin as a gradient or by filtration of the specimen by a nylon sieve. Experience at our institution with the use of electron microscopy for interpretation of fine needle aspiration biopsy samples is briefly reviewed. PMID- 1606887 TI - Rapid ultrastructural examination of FNAs in the diagnosis of intrathoracic tumors. AB - By coupling radiologic imaging procedures with a fine-needle aspiration (FNA) technique, superficial and deep-seated tumors of the thorax may be sampled for cytopathologic evaluation with relative ease, minimal trauma to the patient, and may avert unnecessary or contraindicated surgery. However, the cytodiagnostic limitations that apply to FNA specimens from other sites also obtain for tumors of the thoracic cavity. Although application of histo- and immunohistochemistry offers some expansion of cytodiagnostic limits, their inherent problems of technical failure and biological capriciousness demand a highly critical if not outright skeptical appraisal of the result when applied to cytology specimens. By extending the basic morphologic principles of cytodiagnosis to include fine structure, its limitations can be largely eliminated. Journals of pathology and specialized atlases contain detailed fine structural descriptions of essentially all recognized neoplasms, and the features that discriminate one neoplasm from another are now well recognized. In most instances, a few well-preserved cells or cell groups obtained from an FNA can provide a morphological diagnosis that rivals or surpasses that of conventional paraffin sections of surgically biopsied material, when evaluated in concert with the cytology preparation. PMID- 1606888 TI - Merits of fine-needle aspiration biopsy in children: head and neck. PMID- 1606889 TI - Aspiration cytology of breast fibroadenoma with atypia. PMID- 1606890 TI - FNA cytology of thyroid neurilemmoma (schwannoma) PMID- 1606891 TI - Evaluation of respiratory function in health and disease. AB - From a conceptual standpoint, the tests of pulmonary function can be divided into those that assess the ventilatory function of the lungs and those concerned with gas exchange. Tests of ventilatory function reflect alterations of the elastic resistance and flow resistance of the respiratory apparatus. The elastic properties of the lungs are assessed by determining the position and shape of the curve representing the relationship between the pressure across the lungs and absolute lung volume. When there is reduced distensibility of either the lungs or the chest wall, the volume-pressure curve is shifted down and to the right. The slope of the curve is reduced in the patient with pulmonary fibrosis, while it is normal in the patient with obesity. In asthma (or chronic bronchitis) and emphysema, the volume-pressure curve is shifted up and to the left. In emphysema, the slope of the curve is increased, while it is normal in patients with asthma or bronchitis. In practice, lung volume is used as an index of alterations of the volume-pressure characteristics of the lungs and/or chest wall. The vital capacity is often used as a surrogate for the TLC but it is lower than expected in both restrictive and obstructive disorders. The FEV1.0 reflects the degree of expiratory flow limitation. In a restrictive disorder, lung volume and the FEV1.0 are reduced, but the FEV1.0/FVC ratio is normal. In airflow limitation, lung volume, the FEV1.0, and the FEV1.0/FVC ratio are lower than expected. In airflow limitation, the reversibility with inhaled bronchodilator should be determined. Tests of airway responsiveness are indicated when evaluating patients with unexplained chronic cough, chest tightness, or wheezing, particularly if other lung function tests are normal. The adequacy of gas exchange is assessed by determining the arterial blood gas tensions--PaO2 and PaCO2--and the alveoloarterial pO2 gradient--P(A-a)O2. A lower-than-expected PaO2 can result from several different physiologic disturbances. When alveolar hypoventilation is the sole disturbance, the oxygen in the alveoli and in the blood perfusing them virtually comes into equilibrium, so that the P(A-a)O2 is normal. An elevated P(A a)O2 is caused by either mismatching of ventilation and perfusion, true venous admixture, a diffusion abnormality, or a combination of these disturbances. Because dyspnea on exertion is a cardinal symptom of respiratory disease, exercise tolerance should be assessed. A reduced exercise tolerance may result from ventilatory limitation, impaired gas exchange, cardiac impairment, impaired delivery of the oxygen to the working muscles, or an inability to use the energy. PMID- 1606893 TI - [Clinical and hematological studies in newborn Holstein-Frisian breeding calves with diarrhea in Morocco]. AB - A total of 120 (80 males and 39 females) newborn Holstein-Frisian calves suffering from acute diarrhoea were studied clinically and biochemically, including the following parameters: pH, pCO2, act. HCO3, BE, RBC, PCV, HV, glucose lactate, urea, creatinine, total bilirubin, total protein, AST, Na, K and Cl. The results were interpreted according to their healthy condition, their age as well as their sex. The study had revealed an extreme metabolic acidosis, haemoconcentration, hypoglycaemia and hypofunction in the kidney and liver. Furthermore, the calves with diarrhoea had showed hyponatraemia, hypochloraemia, and hyperkalaemia. Important correlations between clinical and some blood parameters were found. Metabolic acidosis was more severe in male calves than females. These pathophysiological changes should be put in consideration during the therapy of newborn calves suffering from diarrhoea. PMID- 1606892 TI - [Modification of the concentration of creatinine and sodium in blood serum and urine and the fractional elimination of sodium by electrolyte therapy in calves]. AB - In 32 calves, creatinine and sodium concentrations were determined in blood and urine samples taken simultaneously four times during two periods of two days each (control period: milk or milk replacer; trial period: oral electrolyte solution). Creatinine urine/serum ratios and fractional elimination of sodium (FENa) were calculated. The influence of the type of liquid feed on these parameters was evaluated statistically. Calves fed milk replacer had higher urine sodium concentrations and FENa than calves fed whole milk. All parameters determined were influenced by intake of oral electrolyte solution: creatinine concentrations in serum and urine decreased, whereas sodium concentrations in serum and urine, as well as FENa, increased. It is concluded that sodium content of liquid feed significantly influences FENa. PMID- 1606894 TI - Influence of E. coli infection on the disposition kinetic of nalidixic acid in broiler chickens. AB - The pharmacokinetic data of nalidixic acid were investigated in normal and E. coli infected chickens. The highest serum concentration were reached after 2 hours with t0.5 (ab) of (1.706 +/- 0.1 min in normal and 2.030 +/- 0.11 min in diseased) and (1.72 +/- 0.11 min in normal and 1.416 +/- 0.044 in diseased chickens) following oral and intramuscular administration, respectively. The elimination half-life t0.5 (beta) were (2.514 in normal and 2.35 hr in diseased) and (2.567 hr in normal and 2.672 hr in diseased) respectively. Following intravenous injection the kinetic of nalidixic acid followed two compartments open model with t0.5 of (6.27 and 9.15 hr), Vd (0.45 and 0.79 L/kg), Cltot (8.86 and 13.32 ml/kg/min) in normal and E. coli infected chickens, respectively. Administration of nalidixic acid twice daily for 5 successive days in a dose level of 25 mg/kg b. wt. by oral and intramuscular routes showed a cumulative behaviour. PMID- 1606895 TI - A nontoxic derivative of Bothrops jararaca venom suitable to generate antibodies against the native venom. AB - Bothrops jararaca venom was toxoided by stepwise iodination with cold iodine, and doses up to 30 LD50 were non-lethal by i.p. route (BICALHO et al., 1990). Groups of mice injected chronically with the native, or the iodinated venom, have been subjected to histological examination. In the native group, in the spleen, around the white pulp, an acellular, amorphous eosinophilic substance, metachromatic to Methyl Violet, PAS positive, and dichroic to Congo Red under polarized light, was present. Strong congestion in the liver, kidneys and lungs was found. The salivary glands were replenished with an amorphous substance in the serosal acini. The groups injected with the iodinated venom only show discrete alterations, more akin to the control group. The anavenin was immunogenic. Antibody generation in mice and rabbits was detected by ELISA. In mice, active protection against challenge with native venom was presented. The iodinated venom generated a rabbit antiserum with strong lines in gel immunoprecipitation against the lethal venom. A minimum neutralization titer of 2.3 mg ml-1 against the native venom was attained in the first cycle (28 days) of immunization. After 3 cycles (100 days), the protection rose to 5.1 mg ml-1. PMID- 1606896 TI - [The hexobarbital sleeping time in a pharmacologico-toxicological experiment with special reference to age and chronobiologically-limited variations in Wistar rat strain WIST/Lppt]. AB - Investigations were performed to determine the hexobarbital sleeping time (HST) of a strain of Wistar rats (WIST/Lppt). Another aim of the studies was to demonstrate possibilities to use the HST as a method to get additional informations during pharmacological and toxicological experiments. The age--and sex--dependent changes in the hexobarbital sleeping time of the investigated strain of rats are in coincidence with results of other authors, using different rat strains. Additionally, the HST more or less depends on circadian and circannual rhythm. It was stated that the HST as a prescreening-method before starting investigations in detail is of great importance. PMID- 1606897 TI - [The tolerance and residue accumulation of sodium-2,2-dichloropropionate (Dalapon) administered over 90 days to dairy cows]. AB - The influence of the pesticide Sodium-2,2-dichlorpropionate (Na-DCP; Dalapon) was investigated on dairy cows concerning of its effect on ability and health condition. The investigations were carried out in practice using several parameters (feeding, efficiency, haematological and clinicochemical parameters, tests of the slaughtered organisms including their patho-histological examination). The arising of residues was controlled in milk, organs and tissue as well. The pesticide was daily applied orally with the feedstuff in 3 different dosages (2.5, 10, 30 mg/kg b. w./d). Feedstuff consumption, results of milk production and milk quality were not influenced by Na-DCP. The presented results can not verify with safety the insignificant alterations of some clinicochemical parameters (Creatinine, Bilirubin). Direct after the deposit of Dalapon in all samples of milk, organs and tissue residues of this pesticide could be observed. The maximum tolerable residue levels for animal in the ex-GDR were exceeded under these conditions. PMID- 1606898 TI - [The legitimacy of single and group housing of breeding sows]. AB - Current German law on animal rights requires protection and appropriate treatment of animals. However, information on breeding and raising swine is incomplete, and comparison studies of alternative housing systems are needed. Therefore, the effects of single and group housing of pregnant sows on piglet production was investigated in the 120-sow herd of the Institute for Animal Breeding and Husbandry of the University of Kiel. Reproductive traits, general health and behaviour studies were evaluated over one year. Type of housing system was found to have no effect on number of piglets born alive or dead or on days open. Daily gain was influenced. Daily gain of single-housed sows increased but without any difference in feed intake. General health was measured by nutritional condition, soiling, callosity, and injuries at time of evaluation. Single-housed sows had more calluses and were more soiled compared with group-housed sows. Injuries occurred more often in group housing, especially when new animals were integrated into the group. However, injuries were not serious. Animal behaviour was recorded on video during one pregnancy period of 60 sows. The housing system effected "sitting" and "lying" behaviour. Behaviour also is influenced by pregnancy in both housing systems. Equal incidences of abnormal behaviour, considered as sham chewing, were found in both housing systems. PMID- 1606899 TI - Blood and tissue concentrations of trimethoprim following its administration alone and in combination with josamycin. AB - Following a single oral dose of trimethoprim (10 mg/kg b. wt.) in normal fowls, the highest serum concentration achieved 4 hours post-administration with value of 0.64 microgram/ml. The absorption half-life time was 0.64 hours. The elimination half life was 4.73 hours. During repeated oral administration of 10 mg/kg b. wt., once daily for five consecutive days, trimethoprim peaked in serum, 4 h after each dose. Trimethoprim persisted in all fowl's tissues for 96 hours after stopping of drug administration. After oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) in normal fowls, a maximum serum concentration of trimethoprim was recorded at 2 hours with half-life of absorption (t0.5(ab)) valued 0.74 hour. The elimination half-life (t0.5 beta) was 4.37 hours. During repeated oral administration of josamycin (18 mg/kg b. wt.) and trimethoprim (10 mg/kg b. wt.) once daily for five consecutive days in normal fowls, the highest plasma concentrations of trimethoprim occurred 2 hours post each dose. The daily maximum plasma concentrations during the repeated oral administration of both tested drugs were nearly constant. PMID- 1606900 TI - [The social sciences in the training of health personnel]. PMID- 1606901 TI - [The social sciences in the education of the dentist]. PMID- 1606902 TI - [The social sciences and training in health education]. PMID- 1606903 TI - [The University Health Sciences Center: a proposal of the University of Buenos Aires]. PMID- 1606904 TI - [Advances in the strengthening of public health education in the Dominican Republic: the implementation of a collective project]. PMID- 1606905 TI - [Task force for the evaluation of postgraduate programs in social medicine. General report]. PMID- 1606906 TI - [History, social sciences and medical education]. PMID- 1606907 TI - [Combining methods: steps toward a dialectical grasp of interdisciplinary effort]. PMID- 1606908 TI - [The modernization of science and the present national archaism: the case of medical education in Peru]. PMID- 1606909 TI - [Henry Ernest Sigerist--pioneer of the social history of medicine and medical sociology]. PMID- 1606910 TI - [The presence of the social sciences in the education of the nursing professional]. PMID- 1606911 TI - Prediction of the outcome of postoperative hypocalcemia in Graves' disease. AB - Symptomatic hypocalcemia sometimes follows subtotal thyroidectomy for Graves' disease. Irreversible damage to the parathyroids contributes to permanent hypocalcemia and the mechanism for a transient hypocalcemia is thought to be different from that of a permanent one. However, sensitive assays for parathyroid hormones (PTH), which had recently become available, revealed that levels of PTH decrease in patients with transient hypocalcemia. In order to differentiate a prolonged hypocalcemia from a transient one, calcium and inorganic phosphate concentrations in serum as well as in urine, and whole molecule-PTH levels were determined in 18 Graves' disease patients with postoperative hypocalcemia just after the initial symptoms for hypocalcemia appeared. In 13 patients, medication was withdrawn within one month since serum calcium levels had returned to normal (transient hypocalcemia). In five other patients, medication was required for six months or more to maintain normocalcemia (prolonged hypocalcemia). The same parameters were determined after surgery in eight Graves' disease patients without hypocalcemia. Urinary inorganic phosphate concentrations in patients with prolonged hypocalcemia (0.02 +/- 0.01 mmol/mmol Cr) were significantly lower (P less than 0.01) than those in patients with transient hypocalcemia (1.59 +/- 1.59 mmol/mmol Cr) or those in control patients (1.27 +/- 0.70 mmol/mmol Cr). Preoperative concentrations of calcium and inorganic phosphate in serum and urine, and serum alkaline-phosphatase activities were also determined. However, there were no significant differences in these parameters between patients with prolonged and those with transient hypocalcemia. It is concluded that prolonged hypocalcemia is discriminated from the transient type by determining the urinary inorganic phosphate at the time of appearance of the initial symptoms for hypocalcemia.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606912 TI - The renotropic effect of ovine luteinizing hormone on subtotally nephrectomized rats. AB - Some of luteinizing hormone (LH) isoforms can stimulate renal growth. The objective of this study is to determine whether the administration of LH modifies subtotal nephrectomy-induced chronic renal failure. Castrated 3/4-nephrectomized male rats were divided into four groups of seven each and fed a low-protein (6%) diet. Ovine LH with renotropic activity (40 micrograms/day) or vehicle only (control) was given for three weeks or six weeks. Compared with controls, remnant kidney weights (% body weight) in LH-treated rats had increased significantly at three weeks (0.385 +/- 0.019 vs 0.443 +/- 0.052, P less than 0.02), but not at six weeks (0.281 +/- 0.004 vs 0.272 +/- 0.013). 24 h creatinine clearance (ml/day/100 g body weight) increased significantly both by three weeks (242 +/- 58 vs 301 +/- 36, P less than 0.05), and six weeks (323 +/- 55 vs 395 +/- 10, P less than 0.01). Urinary thromboxane B2 excretion increased in LH-treated rats, suggesting that hemodynamic changes may play a role in increasing creatinine clearance. Our results suggest that renotropically active oLH stimulated the glomerular function in castrated rats with reduced renal mass. Further study may clarify its clinical usefulness. PMID- 1606913 TI - Serum intact parathyroid hormone concentration measured by a two-site immunoradiometric assay in normal subjects and patients with various parathyroid disorders. AB - Serum intact parathyroid hormone (PTH) concentration was measured by a two-site immunoradiometric assay (IRMA) in normal subjects and patients with various parathyroid disorders. Serum intact PTH levels were all within the detection limit of the IRMA in normal subjects, and there was a significant negative correlation between serum calcium (Ca) and intact PTH levels. Although 3 out of 26 patients (11.5%) with primary hyperparathyroidism had a normal serum intact PTH concentration, these patients could be readily discriminated from normal subjects by plotting serum intact PTH against the serum Ca concentration. In contrast, serum intact PTH was undetectable in 16 out of 17 patients (94.1%) with idiopathic hypoparathyroidism. Patients with pseudohypoparathyroidism (PHP) type I, mostly under treatment with active vitamin D, exhibited wide distribution of serum intact PTH concentration, and appeared to belong to two distinct subgroups. One group of patients demonstrated a similar relationship between serum intact PTH and Ca levels to normal subjects. The other exhibited much higher serum intact PTH levels despite a normal serum Ca concentration, and no obvious relationship could be observed between the two parameters. These results demonstrate that an inverse relationship between serum Ca and intact PTH can be demonstrated in normal subjects with normocalcemia, that most of the parathyroid disorders can be diagnosed by measuring serum Ca and the intact PTH concentrations simultaneously, and that patients with PHP can be divided into two subgroups: one with a normal relationship between serum Ca and intact PTH, and the other with a high serum PTH level in the face of normocalcemia. PMID- 1606914 TI - Cyclosporine A inhibits the secretion of certain anterior pituitary hormones in patients with nephrotic syndrome. AB - To clarify the effects of cyclosporine A (CsA) on the secretion of serum thyrotropin (TSH), prolactin (PRL), luteinizing hormone (LH) and follicular stimulating hormone (FSH), we performed TRH and LH-RH testing in 4 patients with the nephrotic syndrome before and after the administration of CsA, 6 mg/kg/day for 4 to 12 weeks. Prior to CsA all patients responded normally to TRH with respect to TSH and PRL secretion. Two patients showed normal response of LH and FSH to LH-RH stimulation while the response in 2 other patients, who were both menopausal, was exaggerated. By the third or fourth week of CsA administration the basal and peak TSH and PRL values declined significantly in all patients in response to TRH stimulation while those of LH and FSH showed only a modest decrease in response to LH-RH stimulation. Two to 4 weeks after the cessation of CsA the response of TSH, PRL and FSH returned to the pretreatment level. These observations suggest that: 1) CsA exerts an inhibitory effect on the secretion of at least TSH and PRL in humans, and 2) the effect of CsA on the pituitary may be partially reversible after the cessation of the therapy. PMID- 1606915 TI - Abdominal vagotomy decreased the number of ova shed and serum progesterone levels on estrus in the cyclic hamster. AB - The effects of abdominal vagotomy (AVGT) on ovarian function were studied in cyclic hamsters. AVGT significantly decreased the number of ova shed (AVGT: 10.5 +/- 1.5 ova/hamster, sham: 15.8 +/- 0.7 ova/hamster; P less than 0.05) and serum progesterone levels (AVGT: 2.1 +/- 0.3 ng/ml, sham: 3.9 +/- 0.7 ng/ml; P less than 0.05) on the morning of estrus. However, progesterone concentrations in the corpora lutea and non-luteal ovary on estrus in the AVGT and sham groups were similar. The serum estradiol levels in both groups on proestrus increased from 0900 h (AVGT: 75 +/- 10 pg/ml, sham: 72 +/- 6 pg/ml) to 1500 h (AVGT: 204 +/- 27 pg/ml, sham: 196 +/- 35 pg/ml) but there was no significant difference between the two groups. Partial degranulation of ovarian mast cells was not increased in the AVGT group. Also, vasoactive intestinal peptide (VIP) content in the ovary was not increased by AVGT at 0900 h on proestrus (AVGT: 60.1 +/- 16.8 pg/ovary, sham: 37.2 +/- 14.3 pg/ovary). These results indicated that AVGT interferes with normal ovulation and results in an increase in the number of atretic follicles, but that these effects by AVGT seemed not to be mediated through ovarian mast cells and VIP. PMID- 1606916 TI - Biochemical analysis of the bone of SHC rats with spontaneous hypercholesterolemia and renal dysfunction. AB - Spontaneously hypercholesterolemic (SHC) rats exhibit severe abnormalities in renal function and bone metabolism at old ages, in addition to hypercholesterolemia. SHC rats were also found to show endocrine abnormalities such as hyperthyroidism from young ages. In this study, biochemical and microdensitometric analyses were carried out using femurs to characterize further the abnormality in bone metabolism: whether biochemical markers of the bone may be affected by these abnormalities. At 6 weeks of age, the ashed weight and calcium content of the dried femurs were slightly lower in SHC rats than in age matched Sprague-Dawley (SD) rats. None of the markers of microdensitometric analysis was changed. At 24 weeks of age, the ashed weight of dried femurs and the density of the marrow region of femurs were lower in the SHC rats. The results indicate that SHC rats exhibit severe abnormality in bone metabolism leading to biochemical changes in the bone at old ages whereas changes in bone markers were minimal at young ages before the onset of severe renal dysfunction. PMID- 1606917 TI - In vivo effect of pituitary adenylate cyclase activating polypeptide 38 (PACAP 38) on the secretion of luteinizing hormone (LH) in male rats. AB - In view of the recent demonstrations that pituitary adenylate cyclase activating polypeptide (PACAP) 38 stimulates the release of LH from superfused pituitary cells and that the hypothalamus and anterior pituitary have highly selective binding sites for the peptide, we have surveyed the effect of intraatrial injections of PACAP 38 and vasoactive intestinal peptide (VIP), which has 68% homology with PACAP 38, in intact adult male rats. Furthermore the effect of intracerebroventricular (icv) injection of PACAP 38 was investigated. Intraatrial (10, 30, 100 micrograms) and icv (8, 32 micrograms) administration of PACAP 38 stimulated LH release significantly (P less than 0.01) in a dose-related fashion. Icv injection at a dose of 0.8 microgram was ineffective. The time course pattern of LH release by intraatrial injection and that by icv injection was similar, but the LH levels increased by intraatrial injection were much higher than that by icv injection. Intraatrial administration of VIP had almost no effect on LH release. These findings suggested that PACAP 38 stimulates LH release in vivo. PMID- 1606919 TI - Induction of ovulation and spermatogenesis by hMG/hCG in hypogonadotropic GH deficient patients. AB - Nine female and 20 male hypogonadotropic GH-deficient patients were studied for sexual development by hCG/hMG. In the female patients, gonadotropin therapy was started at the mean age of 22.7 +/- 2.1 years. The administration of progesterone induced withdrawal bleeding at an average of 2.77 +/- 1.94 years after the initiation of hMG/hCG therapy in 8 of the 9 patients studied. Of 6 patients who had been confirmed as positive in a gestagen test, induction of ovulation by hMG/hCG was observed in 5 patients at an average of 5.58 +/- 1.23 years after the onset of therapy, but not in the remaining patient who had been given estrogen and progesterone 4 years 9 months prior to the initiation of the gonadotropin therapy. In male patients, gonadotropin therapy was started at the mean age of 23.6 +/- 5.7 years. Seminal fluid was obtained by masturbation and brought to our clinic in the morning. Of the 20 patients, 19 patients could be observed once a month regularly. Of the 19 patients, spermatozoa could be detected at a mean period of 2.19 +/- 0.87 years after initiation of hCG/hMG therapy in 18, but not in the remaining patient, after 5 years of therapy, who did not receive hCG/hMG regularly. The sperm count exceeded 20 x 10(6)/ml and more in 12 and was lower than that in 8 patients after 3 years of the therapy. No side effects were observed in female patients, but gynecomastia developed in 2 of the 20 male patients. These data suggest that gonadotropin therapy for hypogonadotropic GH deficient patients is effective in promoting ovulation and spermatogenesis despite the initial replacement therapy with sex hormones. PMID- 1606918 TI - A case of asymptomatic cortisol producing adrenal adenoma. AB - We describe a man without the clinical findings of Cushing's syndrome, but who harbored an incidentally found cortisol-producing adrenal adenoma. On adrenal 131I-adsterol imaging, there was good uptake to the nodule, but no visualization of the contralateral adrenal. No abnormalities were found in the basal plasma cortisol, ACTH, urinary free cortisol and 17OHCS. However, dynamic hormone assessment revealed the existence of abnormal cortisol secretion: no suppression to dexamethasone, incomplete response to human corticotropin-releasing hormone, and lack of diurnal variation in plasma cortisol. Left adrenalectomy was performed with the diagnosis of cortisol-producing adrenal tumor. The pathological finding was an adrenal adenoma, and the perifusion of the excised tissues revealed a negligible response of the tumor tissue to ACTH though the residual normal cortex responded. Postoperative course was uneventful without replacement therapy with cortisol. It is suggested that the tumor autonomously produced a small amount of cortisol not only insufficient to provide clinical Cushing's syndrome, but also to provide typical suppression of hypothalamo pituitary corticotroph-adrenal system. PMID- 1606920 TI - Splenic macrophages enhance prolactin and luteinizing hormone action in rat luteal cell cultures. AB - We have reported that splenic macrophages play a role in the regulation of progestin secretion in rats. In this study, splenic macrophages were obtained from cycling rats at different estrous cycle stages and co-cultured with luteal cells from mid-pseudopregnant rats in the absence/presence of prolactin (PRL) or luteinizing hormone (LH). The effect of macrophages on the luteotropic action of PRL and LH was evaluated with 2 parameters, i.e. an increase in total progestin output (progesterone plus 20 alpha-hydroxyprgn-4-en-one [20 alpha-OHP]), and an increase in the progesterone to 20 alpha-OHP (P/20 alpha-OHP) secretion ratio. Splenic macrophages obtained from proestrous or metestrous rats enhanced the PRL action to increase the P/20 alpha-OHP secretion ratio, but those from estrous or diestrous donors did not. Only macrophages from proestrous donors enhanced the PRL action to increase the total progestin output. In contrast, the LH action increasing the P/20 alpha-OHP secretion ratio was enhanced by splenic macrophages regardless of the donors' estrous cycle stages. The LH action increasing the total progestin output was enhanced only by proestrous or metestrous macrophages. Therefore, if luteal cells are co-cultured with proestrous macrophages, the luteotropic actions of PRL and LH can be fully expressed. These results indicate that splenic macrophages directly act on luteal cells and enhance the luteotropic action of PRL and LH, and that this function of splenic macrophages is modified somehow according to the donors' estrous cycle stages. PMID- 1606921 TI - Endocrinological evaluation of GH deficient patient with acromegaloidism showing excessive growth. AB - In this report we describe the first case of a girl with acromegaloidism in Japan. She had large and coarse facial features with acral enlargement accompanying height overgrowth; these resemble the manifestations of acromegaly and gigantism due to growth hormone (GH) overproduction. However, pituitary function studies revealed a dysfunction of her GH secretion. Moreover, markedly decreased serum somatomedin C (SM-C) levels also indicated impairment of GH secretion. Therefore, GH and SM-C cannot have been responsible for promoting somatic growth. However, serum alkaline-phosphatase (Al-P) and osteocalcin, were increased, indicating that stimulation of bone metabolism was increased without GH and SM-C effects. The patient is a typical case showing growth without GH, and these data suggest the existence of an unidentified growth promoting factor that is independent of GH and SM-C. PMID- 1606922 TI - Spontaneous growth hormone secretion in healthy prepubertal children of normal stature. AB - To evaluate the dynamics of growth hormone (GH) secretion in healthy prepubertal children of normal stature, we determined spontaneous GH secretion by measuring GH every 30 min in 21 Japanese subjects, age: 5.4 +/- 2.3 (1.6-10.6) years; height: -1.4 +/- 1.1 (-1.98-1.77) SD. The 24-h mean GH concentration was 4.8 +/- 1.5 ng/ml. The 24-h mean GH was similar in boys and girls (mean +/- SD: 4.8 +/- 1.7 vs 4.7 +/- 1.1 ng/ml). No correlation was found between chronological age and the 24-h mean GH. The 24-h mean GH was closely correlated with GH pulse amplitude (r = 0.94; P less than 0.001), but not with the number of GH pulses. The 24-h mean GH was also highly correlated with 3-h mean GH after sleep and 3-h peak GH after sleep (r = 0.86; P less than 0.001 and r = 0.72; P less than 0.001, respectively). Our data suggest that in healthy prepubertal children of normal stature, (1) spontaneous GH secretion is independent of sex and age, (2) the amount of spontaneous GH secretion is controlled by pulse amplitude, not by number of pulses. (3) 3-h mean GH and 3-h peak GH after sleep might represent 24 h total spontaneous GH secretion. PMID- 1606923 TI - Purification and properties of steroid sulfatase from human placenta. AB - Steroid sulfatase was purified approximately 170-fold from normal human placental microsomes and properties of the enzyme were investigated. The major steps in the purification procedure included solubilization with Triton X-100, column chromatofocusing, and hydrophobic interaction chromatography on phenylsepharose CL-4B. The purified sulfatase showed a molecular weight of 500-600 kDa on HPLC gel filtration, whereas the enzyme migrated as a molecular mass of 73 kDa on sodium dodecyl sulfate polyacrylamide gel electrophoresis. The isoelectric point of steroid sulfatase was estimated to be 6.7 by isoelectric focusing in polyacrylamide gel in the presence of 2% Triton X-100. The addition of phosphatidylcholine did not enhance the enzyme activity in the placental microsomes obtained from two patients with placental sulfatase deficiency (PSD) after solubilization and chromatofocusing. This result indicates that PSD is the result of a defect in the enzyme rather than a defect in the membrane-enzyme structure. Amino acid analysis revealed that the purified human placental sulfatase did not contain cysteine residue. The Km and Vmax values of the steroid sulfatase for dehydroepiandrosterone sulfate (DHA-S) were 7.8 microM and 0.56 nmol/min, while those for estrone sulfate (E1-S) were 50.6 microM and 0.33 nmol/min, respectively. The results of the kinetic study suggest the substrate specificity of the purified enzyme, but further studies should be done with different substrates and inhibitors. PMID- 1606924 TI - Epidemiology: the way ahead? PMID- 1606925 TI - Stringhalt--current thoughts on aetiology and pathogenesis. PMID- 1606926 TI - Ultrasound as a tool in orthopaedics. PMID- 1606927 TI - Factors associated with the risk of developing sarcoid tumours in horses. AB - A retrospective case-control study was conducted to identify risk factors in horses associated with the development of the common skin tumours known as sarcoids. The study involved 503 sarcoid cases diagnosed (January 1980-December 1989) at New York State College of Veterinary Medicine and a similar number of controls (non-sarcoid cases). Data on age, breed and sex of cases and controls were obtained from computerised records. Multiple logistic regression analysis was used to identify risk factors. Separate data were obtained for the same 10 year period from the Veterinary Medical Data Program to determine the proportional morbidity rate at different veterinary colleges in North America. Appaloosa, Arabian and Quarter horses were at a higher risk of developing sarcoid tumours than were Thoroughbred horses. Standardbred horses had a lower risk of developing sarcoids. Geldings were at a higher risk of developing sarcoids in comparison with stallions. There was no significant difference in the risk of developing sarcoids between stallions and mares. The risk of developing sarcoid increased with age up to 15 years and then declined. The proportional morbidity rate of sarcoids among the veterinary colleges ranged between 0 and 14 per 1,000 cases, with an average of 6 per 1,000. PMID- 1606928 TI - Arrhythmias in newborn thoroughbred foals. AB - Foetal electrocardiograms (ECG) were obtained from 39 of 50 Thoroughbred foaling mares close to delivery. The 50 newborn foals were studied electrocardiographically during their adaptive period, immediately after birth. In 48 foals there were paroxysmal arrhythmias or mixed arrhythmias. The most common arrhythmias were sinus arrhythmias including wandering pacemaker (32/50) and atrial premature contraction (30/50). The others observed were atrial fibrillation (15/50), ventricular premature contraction (10/50), partial atrioventricular block (7/50), ventricular tachycardia (4/50), atrial tachycardia (3/50) and idioventricular rhythm (1/50). The duration of the arrhythmias was approximately 5 min, and in all cases the arrhythmia disappeared within 15 min of birth. From foetal ECG recordings, no indication of the likelihood of neonatal arrhythmias was detected. With the exception of 2 cases, all foals have continued to grow and develop normally. These arrhythmias are considered normal physiological processes in newborn Thoroughbred foals during the adaptive period to extra-uterine life. High vagal tone and hypoxaemia at birth are probably the main contributing factors. PMID- 1606929 TI - Pathological aspects of Australian Stringhalt. AB - Nine horses with clinical signs of Australian Stringhalt were killed and tissues collected for a detailed pathological study. Lesions were limited to peripheral nerves and muscles. The most severely affected nerves were the superficial and deep peroneal, distal tibial, plantar digital, volar and recurrent laryngeal nerve with changes characterised by a selective loss of large diameter myelinated fibres with various degrees of demyelination, fibrosis, Schwann cell proliferation and onion-bulb formation. A routine evaluation of the brain and spinal cord by light microscopy failed to reveal any consistent abnormalities. Morphometric analysis of deep peroneal and recurrent laryngeal nerves confirmed the reduced number of large diameter myelinated axons. Teased fibre preparations of these nerves did not show any abnormalities in internodal distance. The most severe muscle lesions were in the long and lateral digital extensors, cranial tibial, dorsal cricoarytenoid, gracilis and lateral deep digital flexor with extensive atrophy of fibres and diffuse fibrosis. Histochemical evaluation of the long digital extensor from 3 affected horses showed an abnormally wide distribution in fibre size and a reduction in type II fibres compared with controls. These lesions are consistent with a distal axonopathy leading to neurogenic muscle atrophy. The distribution of neuromuscular lesions in Australian Stringhalt may be explained by the susceptibility of longer, larger myelinated nerve fibres to injury, but the cause for this distal axonopathy remains unknown. PMID- 1606930 TI - A field study of patterns of unobserved foetal loss as determined by rectal palpation in foaling, barren and maiden thoroughbred mares. AB - Records of 1,009 pregnancies in 574 foaling, barren and maiden Thoroughbred mares on a single stud farm, over a period of 12 years were examined. The farm is situated in the eastern Cape Province of South Africa, at an elevation of 1,800 m, and in an area of climatic extremes. Records of 604 pregnancies in 249 foaling Thoroughbred mares were examined. For these purposes, those pregnancies in which a mare conceived in the same breeding season during which she had foaled were considered as pregnancies in foaling mares. Pregnancy was confirmed by rectal palpation by a single experienced practitioner. Of the 604 pregnancies examined, conceptus attachment occurred in the horn opposite the previously gravid horn in 345 cases (57%), and in the previously gravid horn in 259 cases (43%; P less than 0.005). Unobserved foetal loss after pregnancy diagnosis amounted to 30 (9%) in the former group, while in the latter group (pregnancy established in the postgravid horn) 46 pregnancies were lost (18%; P less than 0.005). This study confirmed that conceptus attachment tends to occur in the uterine horn opposite the previously gravid horn in foaling Thoroughbred mares conceiving during the same season. A significantly higher incidence of foetal loss accompanied conceptus attachment in the postgravid horn. Of 242 pregnancies in 162 previously barren mares, 95 (39%) occurred in the left uterine horn and 147 (61%) in the right horn (P less than 0.005). The incidence of pregnancy failure in this group was 7%. The side of attachment did not affect the rate of loss. Evaluation of the records of 163 maiden mares revealed that conceptus attachment occurred in the left uterine horn in 58 (36%) pregnancies and in the right horn in 105 (64%) pregnancies (P less than 0.005), which is consistent with previously reported observations. Pregnancy failure was recorded in 4% of maiden mares. Side of attachment did not influence rate of loss in this group. PMID- 1606931 TI - Improved insulin sensitivity in hyperinsulinaemic ponies through physical conditioning and controlled feed intake. AB - Ten hyperinsulinaemic ponies divided into conditioned (N = 5) and rested (N = 5) groups were evaluated for their insulin and glucose response following oral glucose administration at Weeks 0, 2, 4, and 6. All ponies received a controlled intake of a pelleted ration during the study. In both groups body weight had decreased from baseline by Week 4 and remained low. After 2 weeks of exercise, ponies in the conditioned group had significantly decreased insulin and glucose indices, including peak insulin response, area under the insulin curve from 0 to 210 min (TIS), and the TIS value: area under the glucose curve from 0 to 210 min. By Week 4 of conditioning, although the insulin and glucose indices continued to decrease in the exercised ponies, there was no significant difference between the groups. Over the first 6 weeks of the study all ponies improved their insulin sensitivity accompanied by a loss of body weight. The conditioned ponies were further evaluated during deconditioning at Weeks 8, 10 and 12. The improved insulin sensitivity was maintained during deconditioning. PMID- 1606932 TI - Ultrasound speed in the metacarpal cortex--a survey of 347 thoroughbreds in training. AB - Transmission ultrasound speed was determined in the third metacarpal bone of 347 Thoroughbred racehorses in training. In addition to direct measurement of apparent ultrasound speed and lateral bone diameter, several derived parameters were estimated (cortical ultrasound speed, corticomedullary ratio and cortical cross-sectional area). Multiple regression equations were developed for each ultrasound measurement using the explanatory variables: sex, age, duration and intensity of training, preparation number and previous shin soreness. The horses (114 females, 82 entire males and 151 geldings ranging in age from 20 to 116 months) had been in continuous training for an average of 10.0 weeks when measurements were made. All measurements except corticomedullary ratio were influenced by the sex of the horse. Geldings had significantly lower ultrasound transmission speed than entire males and females, reflecting a lower bone density. However, the geldings had larger cross-sectional areas (ie bone size). We suggest that the relationship between low ultrasound speed (ie low bone density) and large cross-sectional area maintains the overall mechanical integrity of the metacarpus. This relationship (high ultrasound speed and low cross-sectional area) was also found in each sex group. Ultrasound speed and corticomedullary ratio, but not cross-sectional area, were affected by age. Both duration and intensity of training influenced the ultrasound speed measurements. This study indicated that sex, age and state of training affect ultrasound results, but this explained only about 30% of the variance in the data. Other factors, ie genetic variation in bone density and size, differences in soft tissue thickness and distal limb temperature, presumably account for most of the variance. PMID- 1606933 TI - Contrast-enhanced computed tomography and myelography in six horses with cervical stenotic myelopathy. AB - The cervical spines of 6 horses with cervical stenotic myelopathy (CSM) were examined using myelography and contrast-enhanced computed tomography (CECT). Histopathology of the spinal cord of these horses identified 10 neurologically significant compressive lesions. Myelography and CECT were both able to demonstrate all 10 spinal cord compressive lesions, but myelography falsely identified 2 sites and CECT falsely identified 1 site as compressive lesions of the spinal cord which were not supported by histopathology. Additional qualitative information was obtained by CECT regarding the source, severity and location of spinal cord compression. Computed tomography identified stenosis of the vertebral canal with circumferential loss of contrast agent and documented lateral compressive lesions of the spinal cord due to malformed articular facets. Compression of the peripheral nerve roots by malformed articular facets encroaching on the intervertebral foramen was easily identified by CECT in the axial plane. No compressive lesions were identified in 3 unaffected horses by either method. Minimum sagittal diameter (MSD) values obtained from CECT images were strongly correlated with necropsy measurements, validating CECT as an accurate method of obtaining MSD values. The MSD values in the CSM-affected horses were significantly narrowed (P less than 0.05) from C3C6 regardless of the site of spinal cord compression, when compared with the unaffected controls. This finding supports previous reports suggesting that generalised stenosis of the vertebral canal is an important feature in the pathogenesis of cervical stenotic myelopathy. PMID- 1606934 TI - Inflammatory effects of platelet activating factor (PAF) in equine skin. AB - Intradermal administration of PAF (0.001-1 micrograms/site), but not lyso-PAF (10 micrograms/site), in the horse caused an increase in cutaneous vascular permeability which was maximal by 32 min. Responses to PAF and histamine were reduced by coadministration of the histamine 1 receptor antagonist chlorpheniramine, although only the inhibition of histamine-induced responses was dose-related and statistically significant. The cyclo-oxygenase inhibitor indomethacin was without effect on PAF-induced increases in vascular permeability. These findings suggest that the actions of PAF on equine skin microvasculature may be partly due to histamine release but not to prostanoid formation. Coadministration of prostaglandin (PG) E2 enhanced the oedematous responses to both PAF and histamine, although PGE2 failed to exert direct permeability-increasing activity. In addition, and in contrast to PAF and histamine, PGE2 increased cutaneous blood flow and skin surface temperature. PAF, but not lyso-PAF, also caused neutrophil infiltration into the skin which was maximal at 2 h. No significant effects on eosinophil or mononuclear cell numbers were apparent up to 24 h after injection of PAF. These results are consistent with the concept that PAF may be a mediator of inflammatory disorders of the skin in the horse. PMID- 1606935 TI - Pulmonary artery and aortic pressure changes during high intensity treadmill exercise in the horse: effect of frusemide and phentolamine. AB - Intravenous frusemide (1.0 mg/kg bwt) or phentolamine (0.33 mg/kg bwt) was given to 7 horses 1 h before exercise and their effects on pulmonary artery and aortic pressure changes during strenuous exercise were examined. Short-term near-maximal treadmill exercise (10 m/sec, 3 degrees incline) produced increases in heart rate, mean pulmonary artery pressure (PAP), mean aortic pressure (AP), and packed cell volume (PCV). Frusemide did not affect heart rate, PAP or PCV during exercise. Frusemide significantly decreased mean AP by 10 to 15 mmHg during exercise. Phentolamine produced an increase in heart rate relative to control only early in exercise but not during later, more strenuous, exercise. Phentolamine had no statistically significant effect on AP, PAP, or PCV, but a significant reduction was observed between 180 and 230 sec of exercise when PAP and AP were standardised against heart rate. Frusemide did not prevent horses from haemorrhaging during exercise in this study. Treatment with phentolamine did not sufficiently reduce the PAP and AP to test our hypothesis that a reduction in PAP and AP would eliminate EIPH. PMID- 1606937 TI - Standardised imaging technique for guided M-mode and Doppler echocardiography in the horse. AB - Eighteen echocardiographic images useful for diagnostic imaging, M-mode echocardiography, and Doppler echocardiography of the equine heart were standardised by relating the position of the axial beam to various intracardiac landmarks. The transducer orientation required for each image was recorded in 14 adult horses by describing the degree of sector rotation and the orientation of the axial beam relative to the thorax. Repeatable images could be obtained within narrow limits of angulation and rotation for 14 of the 18 standardised images evaluated. Twenty-seven National Hunt horses were subsequently examined using this standardised technique. Selected cardiac dimensions were measured from two dimensional and guided M-mode studies. Satisfactory results were achieved in 26 of the 27 horses. There was no linear correlation between any of the measured cardiac values and bodyweight. There was no significant difference between measurements taken from the left and the right hemithorax. Six horses were imaged on three consecutive days to assess the repeatability of the measurements. No significant difference was found between measurements obtained on different days. This study demonstrates a method for standardised echocardiographic evaluation of the equine heart that is repeatable, valuable for teaching techniques of equine echocardiography, applicable for diagnostic imaging and quantification of cardiac size, and useful for the evaluation of blood-flow patterns by Doppler ultrasound. PMID- 1606936 TI - Plasma potassium and lactate concentrations in thoroughbred horses during exercise of varying intensity. AB - To investigate the effect of moderate to high intensity exercise of up to 6 min duration on plasma potassium and lactate concentrations, 6 Thoroughbred horses were studied using a treadmill at a 5 degree incline. Each test consisted of an 8 min standardised warm-up followed by an exercise bout at 8, 9, 10 or 12 m/sec. The horses were galloped at each speed for up to a maximum of 6 min or until signs of fatigue were present. The horses were then walked at 0 degree incline. Carotid arterial blood samples were taken during and after the exercise. At 8, 9 and 10 m/sec there was a general pattern of an initial rise in potassium to a peak around 1.5 min of exercise with the concentration then slowly decreasing. At 12 m/sec there was a continuous rise to a peak at the end of exercise in all horses. Immediately after exercise there was a rapid return (within 3-4 min) to the potassium concentrations recorded at the end of the warm-up period. Plasma lactate peaked around the end of exercise at all speeds. At the highest intensity of exercise the mechanisms for the re-uptake of potassium did not appear to be able to match the rate of efflux. In contrast, at less intense work loads, the rate of re-uptake appeared to be similar to or slightly greater than the rate of efflux. It is possible that a disturbance in this balance between efflux and re uptake could result in a disturbance in normal neuromuscular function during exercise. PMID- 1606938 TI - Amniotic fluid analysis for ante-partum foetal assessment in the horse. PMID- 1606939 TI - A percutaneous transtracheal catheter system for improved oxygenation in foals with respiratory distress. PMID- 1606940 TI - Pharmacokinetics of cephradine in neonatal foals after single oral dosing. PMID- 1606941 TI - Diaphragmatic diverticulum (hernia) in a horse. PMID- 1606942 TI - Hypertrophic osteopathy in a Shetland pony attributable to pulmonary squamous cell carcinoma metastases. PMID- 1606943 TI - A study of the transfer of insulin-requiring diabetic patients from U-40 to U-100 Lente insulin. AB - A pilot study of the transfer of insulin-requiring diabetic patients from U-40 to U-100 Lente insulin was conducted in 16 patients. The patients were returned to U 40 after 12 weeks on U-100. There were no adverse events specifically attributable to the process of transfer. The mean blood glucose values for the last day and the last 2 days on U-100 insulin (154.58 +/- 32.09 mg% and 152.99 +/ 29.23 mg% respectively) were significantly lower than those for the corresponding periods on U-40 insulin (178.06 +/- 38.48 mg% and 169.83 +/- 32.34 mg% respectively), (t = 2.79, p = 0.014 and t = 2.30, p = 0.036 respectively). But there was no significant difference between the mean values for the last but one day on U-40 and U-100 (152.36 +/- 27.81 vs 161.59 +/- 33.82; t = 1.16, p = 0.264). There was no significant increase in frequency (2.3 episodes per week on U40 versus 2.8 episodes per week on U-100) or severity of hypoglycaemic attacks with U-100 insulin. On the basis of this experience we feel that transfer from U 40 to U-100 insulin can be achieved without risk of serious adverse consequences provided the transfer is carried out according to a well-designed plan of action. PMID- 1606944 TI - Small intestinal volvulus in adults of Gonder Region, northwestern Ethiopia. AB - A review of intestinal obstruction in Gonder revealed that small intestinal volvulus in adults is the most common cause of small intestinal obstruction, and it ranked only second to sigmoid volvulus as the most common cause of all intestinal obstruction. Out of 25 patients 23 had primary and the remaining 2 secondary small intestinal volvulus. The secondary small intestinal volvulus occurred in patients both of whom had previous gangrenous sigmoid volvulus that was resected. The disease was predominantly seen in young, adult, male farmers. Though early diagnosis is one of the most important factors in the final outcome of the treatment, the diagnostic accuracy preoperatively is said to be low. In this study diagnosis by exclusion of the common causes of small intestinal obstruction in the region improved the preoperative diagnostic accuracy. PMID- 1606945 TI - Chloramphenicol-resistant Salmonella typhi from a patient in Addis Abeba. AB - The clinical history and treatment outcome of a twenty-year old female patient (EN) with typhoid fever is presented. Laboratory examination showed that the etiological agent was a strain of Salmonella typhi which was simultaneously resistant to chloramphenicol (C), streptomycin (S), sulphonamides (Su) and tetracycline (T). Genetic and molecular analysis of this strain demonstrated that resistance to CSSuT was encoded in a plasmid which showed a thermosensitive (28 degrees C) transfer to an Escherichia coli K12 recipient, at a frequency of 4.0 x 10(-2). The R-plasmid had a molecular weight of 110 megadaltons and belonged to incompatibility group H1 plasmids. The present finding should warn medical personnel of the possible dissemination of this epidemic strain in Addis Abeba area. PMID- 1606946 TI - Predictors of moderate to severe dehydration in acute diarrhoeal disease: a case control study. AB - A retrospective, case-control study of predictors of moderate to severe dehydration in patients seen at the Diarrhoeal Disease Control Training Centre, Addis Abeba, Ethiopia, over four years (1986-1989) is presented. A total of 1626 cases with moderate to severe dehydration and an equal number of admission year matched, randomly selected, controls with no clinical evidence of dehydration were analysed. Among the possible predictors considered watery diarrhoea, duration of illness of more than 3 days, high stooling rate, frequent vomiting, fever, early weaning and antecedent protein energy malnutrition (PEM) were found significant. An increase in severity of dehydration when diarrhoea occurred in association with systemic infections, most prominently in infancy, was documented. Use of these findings in the clinical management of patients and in health education of mothers and other care-takers is suggested. Reevaluation of these and other potential predictors by a carefully designed prospective study is proposed. PMID- 1606947 TI - Bacteriological quality of infant feeding bottle-contents and teats in Addis Abeba, Ethiopia. AB - Bacteriological quality of 244 infant feeding-bottles and 61 teats were studied from January 1989 to November 1989. Samples were collected from feeding-bottles of babies who were brought by nursing mothers to clinics and hospitals for varying complaints. Of the 244 bottle-content samples, 144 (59%) harboured more than 2 x 10(6) colonies of bacteria per ml. of samples. The predominant bacterial isolates both from bottle-contents and teat-swabs were the coliform group of bacteria, such as E. coli, Enterobacter spp., Klebsiella spp., and Citrobacter spp. Enteric pathogens such as enteropathogenic E. coli, Shigella spp., S. aureus, and Bacillus cereus, were also isolated from some samples. In some cases enteropathogenic E. coli (EPEC) serotype were isolated both from feeding utensils and from the stools of the bottle-fed babies. Neither the different handling care of bottles used in the studied population, nor the educational status of the nursing mothers made a significant difference in the bacteriological quality of the infant feeding bottles in terms of the total bacterial counts per ml. of the bottle-contents. Preparation of food in advance of need combined with improper storage and inadequate cooking, and poor hygiene could be factors that resulted in a highly contaminated bottle contents. The superior quality of breast milk, and continual teaching of bottle feeding mothers on better handling of feeding bottles and feeds should be constantly emphasized. Teaching mothers on proper handling of feeding utensils accompanied by regular home visiting of health workers to observe hygienic condition of feeding utensils and home environment may improve the prevailing condition. Further and well controlled community based, longitudinal studies are also needed if we are to reduce gastroenteritis in babies as a result of using feeding bottles. PMID- 1606948 TI - Clamydial antibody in sera of patients with trachoma. AB - Serum samples were taken in 1987 from 118 patients with trachoma seen in the Department of Opthalmology of the Gonder College of Medical Sciences, Gonder, Ethiopia, patients being staged according to MacCallan (II, III, IV), and classified in categories of different degrees of inflammation according to Dawson et al. Sera were investigated with the microIF test, using Chlamydia trachomatis serotypes A, B, C and partially D as antigens. Healthy Ethiopian students (n = 14), patients with chlamydial urogenital infections (n = 100), salpingitis (n = 47), and D-seronegative individuals (n = 574) served as controls. Patients with trachoma with severe inflammation showed significantly higher chlamydial antibody titres (greater than or equal to 1:128) against serotype A (p less than 0.05), B (p less than 0.01), and C (p less than 0.01) than patients with trivial, mild or moderate inflammatory symptoms. There was little correlation between MacCallan stages and chlamydial antibody titres, probably due to persistence of antibodies. In the control group of Ethiopian students only single persons were found to react with C. trachomatis serotypes A, B, and C in high titres; the geometric mean varied from x = 1:17 to x = 1:25 and distinctly differed from trachoma patients (x = 1:65). The individuals of other control groups showed high antibody titres against serotype C only in single cases and low geometric mean values. PMID- 1606949 TI - A study of dental problems in diabetic patients. AB - A survey was done in a sample of 105 patients, 45 females and 60 males, from October 1989 to January 1990, in the Diabetes Clinic of Mekane Hiwet Hospital, Asmara, Ethiopia. The objective was to assess the incidence of dental and periodontal problems among diabetic patients. Dental caries was found in 79%, with no significant relation to age of patient or duration of illness. Gingival recession was found in 70.5%, gingival inflammation in 65.7% and loss of attachment in 73.3%; none of them related to age of the patient or duration of diabetes. However, 63.5% of the gingival recession and 78.3% of the gingival inflammation was moderate to advanced, indicating the seriousness of the problem. Females had a significantly higher loss of teeth. These findings show a high incidence of dental and periodontal problems among diabetic patients (in comparison to other observations in Ethiopian non-diabetics), and is suggestive of the adverse influence of diabetes on dental health. Considering the seriousness of the problem, education on oral hygiene and dental care need to be strengthened for diabetic patients. PMID- 1606950 TI - Fluorescence studies of the binding of bacteriophage M13 gene V mutant proteins to polynucleotides. AB - This investigation describes how the binding characteristics of the single stranded DNA-binding protein encoded by gene V of bacteriophage M13, are affected by single-site amino acid substitutions. The series of mutant proteins tested includes mutations in the purported monomer-monomer interaction region as well as mutations in the DNA-binding domain at positions which are thought to be functionally involved in monomer-monomer interaction or single-stranded DNA binding. The characteristics of the binding of the mutant proteins to the homopolynucleotides poly(dA), poly(dU) and poly(dT), were studied by means of fluorescence-titration experiments. The binding stoichiometry and fluorescence quenching of the mutant proteins are equal to, or lower than, the wild-type gene V protein values. In addition, all proteins measured bind a more-or-less co operative manner to single-stranded DNA. The binding affinities for poly(dA) decrease in the following order: Y61H greater than wild-type greater than F68L and R16H greater than Y41F and Y41H greater than F73L greater than R21C greater than Y34H greater than G18D/Y56H. Possible explanations for the observed differences are discussed. The conservation of binding affinity, also for mutations in the single-stranded DNA-binding domain, suggests that the binding to homopolynucleotides is largely non-specific. PMID- 1606952 TI - Complete cDNA sequence of chicken vigilin, a novel protein with amplified and evolutionary conserved domains. AB - The complete cDNA (4375 bp), coding for a new protein called vigilin, was isolated from chicken chondrocytes. The cDNA shows an open reading frame of 1270 amino acids which are organized in 14 tandemly repeated homologous domains. Each domain consists of two subdomains, one with a conserved sequence motif of 35 amino acids (subdomain A) and another one with a presumptive alpha-helical structure of 21-33 amino acids (subdomain B). 149 amino acids at the N-terminus and 71 amino acids at the C-terminus of vigilin do not show the characteristic domain structure. No sequence characteristic of a signal peptide has been found, which argues for an intracellular localisation of vigilin. Vigilin is highly expressed in freshly isolated chicken chondrocytes but little in chondrocytes after prolonged time in culture. Vigilin mRNA exists in two size species, 4.4 kb and 6.5 kb in length due to the usage of different polyadenylation sites. Comparison of the vigilin sequence with data bases showed a remarkable similarity to protein HX from Saccharomyces cerevisiae [Delahodde, A., Becam, A. M., Perea, J. & Jacq, C. (1986) Nucleic Acids Res. 14, 9213-9214]. The yeast protein consists of eight homologous domains with 11 conserved amino acid residues within a set of 35 amino acids. The N-terminal and C-terminal regions of vigilin and protein HX do not reveal any sequence similarity. These results, together with the demonstration of the characteristic vigilin sequence motif in a human cDNA clone, suggest that the repeats represent evolutionary conserved autonomous domains within a family of proteins found in yeast, chicken and man. PMID- 1606951 TI - Characterization of the rat pulmonary surfactant protein A promoter. AB - The expression of the pulmonary surfactant protein A (SP-A) is developmentally regulated and controlled by several hormones. In an attempt to characterize cis acting elements involved in the regulation of SP-A expression, we have cloned the 5' flanking sequence of the rat SP-A gene. The promoter region contains a TATA box but no CAAT box. The transcription start site has been identified by anchored polymerase chain reaction and S1 nuclease mapping of the mature and precursor transcripts. S1 mapping of precursor transcripts has confirmed the stimulating effect of glucocorticoids on SP-A rat gene transcription in vivo. This hormonal effect may be mediated by a putative glucocorticoid responsive element located 140 bp upstream from the initiation site and protected against DNase 1 digestion in footprinting experiments. In vitro transcription of a G-free reporter cassette linked to the 212-bp 5' flanking DNA fragment has established that this putative promoter region is functional. Efficient transcription of the G-free reporter cassette was obtained with cell-free fetal lung extracts, whereas no transcript was detectable with cell-free liver extracts. Comparative analysis of the human and rat 5' flanking sequences shows the presence of strongly conserved motifs, unrelated to previously known consensus sequences. Some of these motifs, specifically protected in DNase 1 footprinting studies, could therefore be involved in the regulation of SP-A gene expression. PMID- 1606953 TI - Three-dimensional structure of proteolytic fragment 163-231 of bacterioopsin determined from nuclear magnetic resonance data in solution. AB - 546 NOESY cross-peak volumes were measured in the two-dimensional NOESY spectrum of proteolytic fragment 163-231 of bacterioopsin in organic solution. These data and 42 detected hydrogen bonds were applied for determining the peptide spatial structure. The fold of the polypeptide chain was determined by local structure analysis, a distance geometry approach and systematic search for energetically allowed side-chain rotamers which are consistent with experimental NOESY cross peak volumes. The effective rotational correlation time of 6 ns for the molecule was evaluated from optimization of the local structure to meet NOE data and from the dependence on mixing time of the NiH/Ci alpha H cross-peak volumes of the residues in alpha-helical conformation. The resulting structure has two well defined alpha-helical regions, 168-191 and 198-227, with root-mean-square deviation 44 pm and 69 pm, respectively, between the backbone atoms in 14 final energy refined conformations. The alpha-helices correspond to transmembrane segments F and G of bacteriorhodopsin. The segment F contains proline 186, which introduces a kink of about 25 degrees with a disruption of the hydrogen bond with the NH group of the following residue. The segments are connected by a flexible loop region 192-197. Torsion angles chi 1 are unequivocally defined for 62% of side chains in the alpha-helices but half of them differ from electron cryo microscopy (ECM) model of bacteriorhodopsin, apparently because of the low resolution of ECM. Nevertheless, the F and G segments can be packed as in the ECM model and with side-chain conformations consistent with all NMR data in solution. PMID- 1606954 TI - Purification, primary structure, bacterial expression and subcellular distribution of an oocyte-specific protein in Xenopus. AB - This study defines a novel Xenopus laevis protein (P100) that has recently been shown to be recognized by scleroderma patient sera. Using a combination of differential solubility in detergents, hydroxyapatite chromatography and one dimensional PAGE, P100 was purified to apparent homogeneity and the amino acid sequence was obtained. An oligonucleotide derived from this sequence was used to clone P100 cDNA through a polymerase-chain-reaction cloning strategy. The entire P100 cDNA sequence was determined, identifying a novel 83,000-Da protein. Two alleles for P100 were transcribed in the oocyte, with only one predicted amino acid change between them. Bacterial expression of a clone containing the entire P100 coding region produced a protein that migrated at a mass 15% greater than that predicted from the amino acid sequence, indicating an aberrant electrophoretic mobility. The mRNA transcript for P100 was only expressed during the previtellogenic stages of oogenesis (stages I and II) and was absent from other Xenopus tissues. Similarly, the P100 protein was found only in Xenopus oocytes and was localized to the cytoplasm of these cells. P100 irreversibly bound single-stranded-DNA--cellulose but not double-stranded-DNA--cellulose. These data demonstrate the presence of a novel oocyte-specific protein in Xenopus. PMID- 1606955 TI - The binding of triazine herbicides to the photosynthetic reaction center of Rhodopseudomonas viridis. Energy minimization studies. AB - The binding of six herbicides of the triazine family to the photosynthetic reaction center of Rhodopseudomonas viridis was investigated with energy minimization techniques, in order to correlate experimental with calculated data. The inhibitors were modeled in the active site according to the X-ray structure analysis of the complex formed between the triazine terbutryn (2-ethylamino-4-t butylamino-6-methylthio-s-triazine) and the reaction center of R. viridis [Michel, H., Epp. O. & Deisenhofer, J. (1986) EMBO J. 5, 2445-2451]. 40 different energy minimizations were carried out with varying cutoff radii, partial charges on inhibitor atoms and dielectric constants, i.e. 10 different combinations of these were tested. The impact of these parameters on the calculated binding and interaction energy was either examined for all protein/triazine complexes or, in the case of the dielectric constant, a smaller sample was used. The calculated energies are dominated by van der Waals interactions, which change by up to 20% when extending the cutoff radius from 0.8 nm to 1.5 nm. The use of uniform or distance-dependent dielectric constant or partial charges on the inhibitor atoms does not severely influence the resulting structures, but shows a great impact on the calculated energies. In the two groups of triazines, each containing three inhibitors with methoxy or methylthio substituents, correlations of biological and calculated data were found quite often, but only once with all six triazines. The energy-minimized structures were compared and analysed. A third hydrogen bond, not seen in the X-ray analysis of the reaction center/tertubryn complex, was found between the t-butylamino moiety of terbutryn (and equivalent moieties in the other triazines) and the carbonyl oxygen of TyrL222. PMID- 1606956 TI - C-terminal sequencing of protein. A novel partial acid hydrolysis and analysis by mass spectrometry. AB - Peptides or proteins were hydrolyzed by vapors of 90% pentafluoropropionic acid or heptafluorobutyric acid at 90 degrees C for various time periods. The hydrolyzate mixtures analyzed by both fast-atom-bombardment and electrospray ionization mass spectrometry showed a series of C-terminal successive degradation molecular ions. The degradation reaction may be due to the selective formation of an oxazolone ring at the C-terminal amino acid, followed by hydrolytic removal of the C-terminal amino acid. The major side reactions were cleavages of the peptide bonds at the C side of the internal aspartic acid residue and the N side of serine residue. PMID- 1606957 TI - Substitution of ASP193 to ASN at the active site of ribulose-1,5-bisphosphate carboxylase results in conformational changes. AB - The crystal structure of a mutant of ribulose bisphosphate carboxylase/oxygenase from Rhodospirillium rubrum, where Asp193, one of the ligands of the magnesium ion at the activator site, is replaced by Asn, has been determined to a nominal resolution of 0.26 nm. The mutation of Asp to Asn induces both local and global conformation changes as follows. The side chain of Asn193 moves away from the active site and interacts with main-chain oxygen of residue 165, located in the neighbouring strand beta 1 of the alpha/beta barrel. The side chain of Lys166, which forms a salt bridge with Asp193 in the wild-type enzyme, interacts with Asn54 from the second subunit and creates a new subunit-subunit interaction. Another new subunit-subunit interaction is formed, more than 1.2 nm away from the site of the mutation. In the mutant enzyme, the side chain of Asp263 interacts with the side chain of Thr106 from the second subunit. Asp193 is not part of a subunit-subunit interface area or an allosteric regulatory site. Nevertheless, replacement of this residue by Asn results, unexpectedly, in a difference in the packing of the two subunits, which can be described as a slight rotation of one of the subunits relative to the second. The observed structural changes at the active site of the enzyme provide a molecular explanation for the differing behaviour of the Asp193----Asn mutant with respect to activation. PMID- 1606958 TI - Reversed micelles of polymeric surfactants in nonpolar organic solvents. A new microheterogeneous medium for enzymatic reactions. AB - A new microheterogeneous non-aqueous medium for enzymatic reactions, based on reversed micelles of a polymeric surfactant, was suggested. The surfactant termed CEPEI, was synthesized by successive alkylation of poly(ethyleneimine) with cetyl bromide and ethyl bromide and was found to be able to solubilize considerable amounts of water in benzene/n-butanol mixtures. The hydrodynamic radius of polymeric-reversed micelles was estimated to be in the range 22-51 nm, depending on the water content of the system, as determined by means of the quasi-elastic laser-light scattering. Polymeric reversed micelles were capable of solubilizing enzymes (alpha-chymotrypsin and laccase) in nonpolar solvents with retention of catalytic activity. Due to the strong buffering properties of CEPEI over a wide pH range, it could maintain any adjusted pH inside hydrated reversed micelles. It was found that catalytic behavior of enzymes entrapped in polymeric reversed micelles was rather insensitive to the pH of the buffer solution introduced into the system as an aqueous component, but determined mostly by acid-base properties of the polymeric surfactant itself. Both catalytic activity and stability of entrapped alpha-chymotrypsin and laccase were found to increase with increasing water content of the system. Under certain conditions, the entrapment of alpha chymotrypsin into CEPEI reversed micelles resulted in a considerable increase in catalytic activity and stability as compared to aqueous solution. CEPEI reversed micelles were demonstrated to be promising enzyme carriers for use in membrane reactors. Owing to the large dimensions of CEPEI reversed micelles, they are effectively kept back by a semipermeable membrane, thus allowing an easy separation of the reaction product and convenient recovery of the enzyme. PMID- 1606959 TI - Phosphatidylinositol-glycan-specific phospholipase D is an amphiphilic glycoprotein that in serum is associated with high-density lipoproteins. AB - Phosphatidylinositol (PtdIns)-glycan-specific phospholipase D was purified from bovine and human serum by phase separation in Triton X-114 and by chromatography on DEAE-cellulose, octyl-Sepharose, concanavalin-A-Sepharose, and hydroxyapatite. The purification of the two enzymes was approximately 1200-fold with a recovery of 3-5%. Bovine serum contained about 40 micrograms/ml of PtdIns-glycan-specific phospholipase D, about 10 times more than the amount determined in human serum. PtdIns-glycan-specific phospholipase D is also present in mammalian cerebrospinal fluid and in mammalian milk but to a much lesser extent than in serum. Enzyme from bovine and human serum displayed amphiphilic properties as revealed by sucrose density gradient centrifugation and gel filtration in the absence and presence of detergent. On density gradient centrifugation, both enzymes sedimented with an apparent sedimentation coefficient of about 6.0 S in the presence of 0.1% Triton X-100, and formed aggregates up to 14.5 S in the absence of detergent. Upon gel filtration, the bovine and human enzymes migrated with a Stokes' radius of 6.5 nm and 6.6 nm, respectively, in the presence of Triton X 100. In the absence of Triton X-100, both enzymes gave a Stokes' radius of 8.8 nm. Serial centrifugation of serum at increasing NaBr concentrations revealed that the majority of the enzyme is contained in the high-density lipoprotein fraction. PtdIns-glycan-specific phospholipase D from bovine and human serum contained 27 and 28 N-acetylglucosamine residues, respectively. Treatment with N glycosidase F decreased the apparent molecular mass of the bovine and human enzyme from 115 and 123 kDa to 91 and 87 kDa, respectively. Sequence analysis of peptides derived from PtdIns-glycan-specific phospholipase D of bovine serum by CNBr cleavage gave 100% identity to the sequence published for the bovine liver enzyme while there was 83% similarity and 74% identity to the sequence of peptides obtained from the human serum enzyme. PMID- 1606960 TI - Selenoprotein synthesis in E. coli. Purification and characterisation of the enzyme catalysing selenium activation. AB - The product of the selD gene from Escherichia coli catalyses the formation of an activated selenium compound which is required for the synthesis of Sec-tRNA (Sec, selenocysteine) from Ser-tRNA and for the formation of the unusual nucleoside 5 methylaminomethyl-2-selenouridine in several tRNA species. selD was overexpressed in a T7 promoter/polymerase system and purified to apparent homogeneity. Purified SELD protein is a monomer of 37 kDa in its native state and catalyses a selenium dependent ATP-cleavage reaction delivering AMP and releasing the beta-phosphate as orthophosphate. The gamma-phosphate group of ATP was not liberated in a form able to form a complex with molybdate. It was precluded that any putative covalent or non-covalent ligand of SELD not removed during purification participated in the reaction. In a double-labelling experiment employing [75Se]selenite plus dithiothreitol and [gamma-32P]ATP the 75Se and 32P radioactivities co-chromatographed on a poly(ethyleneimine)-cellulose column. No radioactivity originating from ATP eluted in this position when [alpha-32P]ATP or [beta-32P]ATP or [14C]ATP were offered as substrates. The results support the speculation that the product of SELD is a phosphoselenoate with the phosphate moiety derived phosphoselenoate from the gamma-phosphate group of ATP. The alpha,beta cleavage of ATP is also supported by the finding that neither adenosine 5'-[alpha,beta-methylene]triphosphate nor adenosine 5'-[beta,gamma methylene]triphosphate served as substrates in the reaction. PMID- 1606961 TI - The pro-region of the yeast prepro-alpha-factor is essential for membrane translocation of human insulin-like growth factor 1 in vivo. AB - Four yeast secretion signals, the 19-amino-acid invertase signal sequence, the 17 amino-acid acid-phosphatase signal sequence, and the pre-sequence and prepro sequence of prepro-alpha-factor have been used to look for the secretion of recombinant human insulin-like growth factor 1 (IGF1) from Saccharomyces cerevisiae. Only the prepro-sequence, often referred to as the alpha-factor leader and consisting of an N-terminal 19-amino-acid pre-sequence or signal sequence attached to a 66-amino-acid pro-region, permits secretion of IGF1. The signal sequences alone do not allow the translocation of IGF1 into the endoplasmic reticulum. This is evident from the fact that IGF1-like molecules, to which the signal sequences are still attached, accumulate intracellularly in the cytosol. Fusion of the pro-region of the alpha-factor leader to the C-terminus of the acid-phosphatase and invertase signal sequences allows IGF1 to be secreted once again. These results reveal the essential role of the pro-region of the alpha-factor leader in the secretion of IGF1 and indicate that it may have a function in guiding a nascent IGF1 polypeptide to a state in which translocation can occur. PMID- 1606962 TI - The carboxylesterase family exhibits C-terminal sequence diversity reflecting the presence or absence of endoplasmic-reticulum-retention sequences. AB - Resident proteins of the endoplasmic reticulum lumen are continuously retrieved from an early Golgi compartment by a receptor-mediated mechanism. The sorting or retention sequence on the endoplasmic reticulum proteins is located at the C terminus and was initially shown to be the tetrapeptide KDEL in mammalian cells and HDEL in Saccharomyces cerevisiae. The carboxylesterases are a large family of enzymes primarily localized to the lumen of the endoplasmic reticulum. Retention sequences in these proteins have been difficult to identify due to atypical and heterogeneous C-terminal sequences. Utilizing the polymerase chain reaction with degenerate primers, we have identified and characterized the C-termini of four members of the carboxylesterase family from rat liver. Three of the carboxylesterases sequences contained C-terminal sequences (HVEL, HNEL or HTEL) resembling the yeast sorting signal which were reported to be non-functional in mammalian cells. A fourth carboxylesterase contained a distinct C-terminal sequence, TEHT. A full-length esterase cDNA clone, terminating in the sequence HVEL, was isolated and was used to assess the retention capabilities of the various esterase C-terminal sequences. This esterase was retained in COS-1 cells, but was secreted when its C-terminal tetrapeptide, HVEL, was deleted. Addition of C-terminal sequences containing HNEL and HTEL resulted in efficient retention. However, the C-terminal sequence containing TEHT was not a functional retention signal. Both HDEL, the authentic yeast retention signal, and KDEL were efficient retention sequences for the esterase. These studies show that some members of the rat liver carboxylesterase family contain novel C-terminal retention sequences that resemble the yeast signal. At least one member of the family does not contain a C-terminal retention signal and probably represents a secretory form. PMID- 1606963 TI - Ascorbate-mediated transmembrane electron transport and ascorbate uptake in leukemic cell lines are two different processes. AB - Transmembrane reduction of extracellular oxidants by K562 and U937 leukemic cells was stimulated by catalytic amounts of ascorbate or dehydroascorbate. This stimulation was not due to transport of ascorbate in different redox states in and out of the cells. The membrane redox cycle was strictly dependent on the presence of the cells at every stage, and showed high affinity for ascorbate with simple linear kinetics. Metabolic inhibitors and sulfhydryl reagents inhibited this stimulation. Ascorbate uptake was also dependent on oxidation, but in a very different manner and with much lower affinity for ascorbate. The uptake was non saturable in the concentration range used. There was some release of ascorbate from the cells, which cannot account for an appreciable part of the reduction of extracellular electron acceptors. PMID- 1606964 TI - cDNA cloning and deduced amino acid sequence of a major, glycine-rich cuticular protein from the coleopteran Tenebrio molitor. Temporal and spatial distribution of the transcript during metamorphosis. AB - In Coleoptera, the elytra (forewings), with a very hard and thick cuticle, protect the membranous and delicate hindwings against mechanical stress. We have isolated and characterized a cDNA encoding a major cuticle protein in Tenebrio molitor, named ACP-20. The deduced amino acid sequence is roughly tripartite, with two terminal glycine-rich domains and a central region showing pronounced similarities with some other hard cuticle proteins. Northern blot and in situ hybridization analyses reveal that ACP-20 gene expression is developmentally regulated since transcript accumulation occurs only in epidermal regions synthesizing hard cuticle and is restricted to the period of preecdysial adult cuticle deposition. Moreover, application of a juvenile hormone analogue prevents the appearance of the transcript, indicating that juvenile hormone, a key molecule involved in the control of insect metamorphosis, negatively regulates the expression of the ACP-20 gene. PMID- 1606965 TI - Stimulation of phospholipase C by guanine-nucleotide-binding protein beta gamma subunits. AB - We have previously shown that soluble fractions obtained from human HL-60 granulocytes contain a phospholipase C which is markedly stimulated by the stable GTP analogue guanosine 5'-[3-O-thio]triphosphate (Camps, M., Hou, C., Jakobs, K. H. and Gierschik, P. (1990) Biochem. J. 271, 743-748]. To investigate whether this stimulation was due to a soluble alpha subunit of a heterotrimeric guanine nucleotide-binding protein or a soluble low-molecular-mass GTP-binding protein, we have examined the effect of purified guanine-nucleotide-binding protein beta gamma dimers on the phospholipase-C-mediated formation of inositol phosphates by HL-60 cytosol. We found that beta gamma subunits, purified from bovine retinal transducin (beta gamma t), markedly stimulated the hydrolysis of phosphatidylinositol 4,5-bisphosphate by this phospholipase C preparation. The stimulation of phospholipase C by beta gamma t was not secondary to a phospholipase-A2-mediated generation of arachidonic acid, was prevented by the GDP-liganded transducin alpha subunit and was additive to activation of phospholipase C by guanosine 5'-[3-O-thio]triphosphate. Beta gamma t also stimulated soluble phospholipase C from human and bovine peripheral neutrophils, as well as membrane-bound, detergent-solubilized phospholipase C from HL-60 cells. Stimulation of soluble HL-60 phospholipase C was not restricted to beta gamma t, but was also observed with highly purified beta gamma subunits from bovine brain. Fractionation of HL-60 cytosol by anion-exchange chromatography revealed the existence of at least two distinct forms of phospholipase C in HL-60 granulocytes. Only one of these forms was sensitive to stimulation by beta gamma t, demonstrating that stimulation of phospholipase C by beta gamma subunits is isozyme specific. Taken together, our results suggest that guanine-nucleotide binding protein beta gamma subunits may play an important and active role in mediating the stimulation of phospholipase C by heterotrimeric guanine-nucleotide binding proteins. PMID- 1606966 TI - Chemical cross-linking indicates a staggered and antiparallel protofilament of desmin intermediate filaments and characterizes one higher-level complex between protofilaments. AB - Tetrameric rods, protofilaments and assembled filaments of desmin, the intermediate filament protein of muscle, have been chemically cross-linked with the lysine specific cross-linkers EGS [ethylene glycol bis(succinimidylsuccinate), 1.61 nm span] and bis(sulfosuccinimidyl) suberate (1.14 nm span). One bis(sulfosuccinimidyl)suberate and two EGS cross-links were isolated from the rod and characterized. They show that the two coiled coils in the rod tetramer are staggered by approximately 15-20 nm and strongly indicate an antiparallel arrangement in which the inner overlapping part of the rod is formed by the amino-terminal helices 1A, 1B and 2A. Both EGS cross-links identified in the rod were also isolated from cross-linked filaments. The isolated rod, therefore, represents a complex also present in identical, or very similar form in protofilaments and in assembled filaments. Cross-linked filaments yielded a third EGS cross-link that must have been formed between neighboring protofilaments. It connects the highly conserved carboxy-terminus of helix 2B of the first protofilament to the overlap region formed by helices 1A and 2A of the second protofilament. The restrictions posed by these cross-links on current filament models are discussed. PMID- 1606967 TI - Mitochondrial dolichyl-phosphate mannose synthase. Purification and immunogold localization by electron microscopy. AB - Mitochondrial dolichyl-phosphate mannose synthase has been purified to homogeneity using an original procedure, reconstitution into specific phospholipid vesicles and sedimentation on a sucrose gradient as final step. The enzyme has an apparent molecular mass of 30 kDa on an SDS/polyacrylamide gel. Increased enzyme activity could be correlated with this polypeptide band. A specific antibody was raised in rabbits against this transferase. Specific IgG obtained from the immune serum removed enzymatic activity from a detergent extract of mitochondrial outer membrane and reacted specifically with the 30-kDa band on immunoblots. Furthermore, an immunocytochemical experiment proved the localization of dolichyl-phosphate mannose synthase on the cytosolic face of the outer membrane of mitochondria. PMID- 1606968 TI - Isolation and characterization of three chitinases from Trichoderma harzianum. AB - Three proteins which display chitinase activity were purified from the supernatants of Trichoderma harzianum CECT 2413 grown in minimal medium supplemented with chitin as the sole carbon source. Purification was carried out after protein precipitation with ammonium sulphate, adsorption to colloidal chitin and digestion, and, finally, chromatofocusing. By this procedure, two chitinases of 42 kDa (CHIT42) and 37 kDa (CHIT37) were purified to homogeneity, as judged by SDS/PAGE and gel filtration, whereas a third, of 33 kDa (CHIT33), was highly purified. The isoelectric points for CHIT42, CHIT37 and CHIT33 were 6.2, 4.6 and 7.8, respectively. The three enzymes displayed endochitinase activities and showed different kinetic properties. CHIT33 was able to hydrolyze chitin oligomers of a polymerization degree higher than n = 4, its Km for colloidal chitin being 0.3 mg/ml. CHIT42 and CHIT37 were able to hydrolyze chitin oligomers with a minimal polymerization degree of n = 3, their Km values for colloidal chitin being 1.0 mg/ml and 0.5 mg/ml respectively. With regard to their lytic activity with purified cell walls of the phytopathogenic fungus Botrytis cinerea, a hydrolytic action was observed only when CHIT42 was present. Antibodies against CHIT42 and CHIT37 specifically recognized the proteins and did not display cross-reaction, suggesting that each protein is encoded by a different gene. PMID- 1606969 TI - Requirement of N- and C-terminal regions for enzymatic activity of human T-cell leukemia virus type I protease. AB - The requirement of N- and C-terminal regions for the enzymatic activity of human T-cell leukemia virus type I (HTLV-I) protease was investigated using a series of deletion mutants. The activity was analyzed by autoprocessing of the protease itself or by processing of the gag p53 precursor. The deletional analyses indicated that Asp38-Gly152 with an additional Met-Pro sequence at the N-terminus was probably sufficient for the enzymatic activity, although the mature HTLV-I protease consists of Pro33-Leu157. A molecular model of HTLV-I protease, which was constructed by comparison with the structure of Rous sarcoma virus protease, predicted that Pro33-Leu37 and Gly143-Leu147 would form a beta-sheet. Our experimental results and the model structure suggest that (a) five amino acids in the N-terminal region (Pro33-Leu37), which are thought to be involved in the beta sheet, are not crucial for the enzymatic activity; (b) Pro153-Leu157 is not necessary but Pro148-Gly152 is important for the enzymatic activity, in addition to Gly143-Leu147 involved in the beta-sheet. PMID- 1606970 TI - Structural and functional characterization of Escherichia coli peptidyl-prolyl cis-trans isomerases. AB - Peptidyl-prolyl cis-trans isomerases (PPIases), enzymes that catalyze the cis trans isomerization of peptide bonds to which proline contributes the nitrogen, were purified from Escherichia coli. In this organism, at least two PPIases are present. Both the cationic (periplasmic) and anionic (cytoplasmic) PPIases are inhibited by cyclosporin A with a Ki of 25-50 microM, a concentration 1000-fold higher than that required for eukaryotic PPIases. Although isoelectric focusing indicates that the two enzymes differ in isoelectric point by at least 4.0 pH units, the specific activities of the enzymes toward the tetrapeptide substrate succinyl-Ala-Ala-Pro-Phe-methyl-coumarylamide are equivalent. The activity of both enzymes for a series of substituted succinyl-Ala-Xaa-Pro-Phe-para nitroanilide tetrapeptides suggests that the structure and function of the active site of the prokaryotic proteins is similar to that of eukaryotic cyclophilins. Both enzymes are capable of catalyzing the refolding of thermally denatured type III collagen. Antibodies against the periplasmic PPIase do not recognize the cytoplasmic enzyme, indicating significant differences in epitopes between the two forms. Circular dichroism spectroscopy indicates that the secondary structure of the cationic protein consists of 17% alpha-helix, 34% beta-sheet, 17% turns, 33% random coil and is very similar to human cytosolic PPIase. PMID- 1606971 TI - Unique structure in the intergenic and 5' external transcribed spacer of the ribosomal RNA gene from the pea aphid Acyrthosiphon pisum. AB - We analyzed the DNA sequence of the 5' external transcribed spacer (ETS) and part of the intergenic transcribed spacer (IGS) of the aphid ribosomal RNA gene (rDNA). The 5' ETS of aphid rDNA consists of 843 nucleotides with a G/C content of 69 mol/100 mol, far higher than that of any other known 5' ETS for insect rDNA. The IGS of aphid rDNA contained a characteristic array of repeated sequences of 247 nucleotides. The repeated sequences were identical. It was shown that the number of the repeating sequence is heterogeneous. PMID- 1606972 TI - The legumin precursor from white lupin seed. Identity of the subunits, assembly and proteolysis. AB - The precursors of the legumin-like storage protein from developing white lupin seeds (35 days after flowering) are trimers composed of protomers of M(r) 72,000 or 67,000. Some subunits of these oligomers contain processed precursor polypeptides, namely alpha polypeptides of either 52,000 or 44,000 linked through disulphide bonds to a beta polypeptide of 21,000, typical of the mature legumin. The prolegumin is glycosylated. Legumin oligomers purified from the same seeds are both trimers and hexamers; some of their subunits are still made of precursor polypeptides. The hexamer contains less precursor polypeptide than the trimer. A low level or absence of precursor appears to be a condition of hexamer assembly. The heterogenous prolegumin and legumin oligomers represent intermediates in the processing of the prolegumin to mature legumin. Hydrophobic-interaction chromatography on TSK-phenyl-5PW and titration with the hydrophobic probe 8 anilino-1-naphthalenesulphonate indicate that the legumin is less hydrophobic than the prolegumin. This is attributed to structural rearrangements at processing of the propolypeptide, made evident by the behaviour in CD and by the second-derivative ultraviolet spectra of the two proteins. The total protein extract of developing cotyledons at 40 days after flowering contains endopeptidases, similar to those existing in the resting seeds, which cause a limited cascade degradation of the prolegumin and legumin. PMID- 1606974 TI - Defining the role of protein kinase c in calcium-ionophore-(A23187)-mediated activation of phospholipase A2 in pulmonary endothelium. AB - We sought to investigate the mechanisms by which the calcium ionophore A23187 triggers arachidonic acid release in bovine pulmonary endothelial cells and to test the hypothesis that protein kinase C is involved in this process. Our results indicate that the mechanism by which A23187 increases phospholipase A2 activity and arachidonic acid release in bovine pulmonary arterial endothelial cells depends upon the concentration studied. At concentrations of 1 microM and 2.5 microM, A23187 increases phospholipase A2 activity and arachidonic acid release without stimulating protein kinase C. At concentrations of 5-12.5 microM, A23187 increases arachidonic acid release and phospholipase A2 activity in conjunction with a dose-dependent activation of membrane-bound protein kinase C. To test the hypothesis that these doses of A23187 increase phospholipase A2 activity by stimulating protein kinase C, we studied the effect of prior treatment with the protein kinase C inhibitor sphingosine. Sphingosine inhibits the increase in phospholipase A2 activity and arachidonic acid release caused by A23187 over the range 5-12.5 microM. To investigate further the potential role of protein kinase C, we studied the effects of the inactive phorbol ester 4 alpha phorbol 12 beta-myristate 13 alpha-acetate (4 alpha-PMA) and an active phorbol ester 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (4 beta PMA). Neither 4 alpha-PMA nor 4 beta-PMA affected basal arachidonic acid release. 4 alpha-PMA also did not augment the effects of A23187. In contrast, 4 beta-PMA significantly augments the increase in phospholipase A2 activity and arachidonic acid release caused by lower doses of A23187. Under these conditions, sphingosine completely inhibits the stimulatory effects of 4 beta-PMA on protein kinase C translocation, phospholipase A2 and arachidonic acid release. Thus, at low doses (1 microM and 2.5 microM) A23187 increases phospholipase A2 activity and arachidonic acid release by a mechanism that does not involve protein kinase C. At these A23187 doses, activating membrane-bound protein kinase C with 4 beta-PMA causes a synergistic increase in phospholipase A2 activity and arachidonic acid release. At higher doses (5-12.5 microM), A23187 acts in large part by stimulating protein kinase C translocation. Overall, our results indicate that activating membrane bound protein kinase C by itself is an insufficient stimulus to increase phospholipase A2 activity and arachidonic acid release in pulmonary endothelial cells, but activating protein kinase C can substantially augment the increase in phospholipase A2 activity and arachidonic acid caused by a small increase in intracellular calcium. PMID- 1606973 TI - Yeast actin is relatively well behaved. AB - Actin from yeast has been reported previously to have unusual polymerization properties. Here we report a simple sensitive spot assay for actin and use it to develop a high-yield procedure for the purification of actin from the yeast Saccharomyces cerevisiae. The polymerization properties of purified yeast actin are quantitatively similar to all other characterized actins. We have characterized this actin with respect to its ability to interact with yeast profilin and tropomyosin, the only yeast actin-binding proteins so far purified and characterized. Yeast profilin can sequester yeast actin monomers and thereby reduce the ability of yeast actin to polymerize, whereas it has little effect on the degree of polymerization of rabbit skeletal muscle actin. By contrast, there is no apparent difference between the binding of yeast or smooth muscle tropomyosin to yeast or rabbit skeletal muscle actin. The availability of purified yeast actin should facilitate a detailed examination of its interaction with recently discovered yeast actin-binding proteins. Greer and Schekman (1982) [Greer, C. & Schekman, R. (1982), Mol. Cell Biol. 2, 1279-1286] reported that an intrinsic property of yeast actin is a Ca2+ dependent increase in critical concentration with the formation of 15-50-nm particles. Our purified actin does not have this property. By modifying the purification protocol, we can obtain a preparation having a Ca(2+)-dependent change in polymerization properties. The Ca(2+)-dependent effect results in a slower polymerization rate as well as the formation of shorter filaments. Since this effect could be mediated by a protein present at a very low stoichiometry to actin, and we do not see any contaminating peptides, we have not pursued this effect further. We suggest that the Ca(2+) dependent properties of the Greer and Schekman preparation are most likely due to a minor contaminant. PMID- 1606976 TI - Transurethral resection syndrome. A prospective study. AB - Significant hyponatraemia has been reported following transurethral prostatectomy (TURP) in 11-41% of cases. The majority of previous studies have been performed retrospectively. A prospective study was undertaken of 100 patients undergoing TURP. In all, a 24-Charr sheath with non-irrigating, resectoscope and 1.5% glycine as irrigant was used. Volume of irrigant used, weight of prostate and length of procedure were recorded. Serum electrolytes were measured at anaesthetic induction and immediately on transfer to the recovery room. In none of the 100 patients was there a statistically significant fall in serum sodium following resection. No clinical changes of transurethral resection (TUR) syndrome occurred. This study confirms that TUR syndrome and a significant fall in serum sodium can be virtually prevented in TURP and the use of an irrigating resectoscope or a trocar in the average case is not necessary. PMID- 1606975 TI - Disulfide arrangement of human insulin-like growth factor I derived from yeast and plasma. AB - The disulfide arrangement of yeast derived human insulin-like growth factor I (yIGF-I) was determined using a combination of Staphylococcus aureus V8 protease mapping, fast-atom-bombardment mass spectrometry as well as amino acid sequence and composition analysis. Three disulfide bridges were found between the following cysteine residues: Cys6-Cys48, Cys47-Cys52 and Cys18-Cys61. IGF-I isolated from human plasma (pIGF-I) was found to have an identical disulfide configuration. A yeast-derived isomeric form of IGF-I (yisoIGF-I) exhibited an altered disulfide arrangement: Cys6-Cys47, Cys48-Cys52 and Cys18-Cys61. Radioreceptor analysis of pIGF-I and yIGF-I showed high specific activity, 20,000 U/mg. However, yisoIGF-I demonstrated a severely reduced ability to bind to the IGF-I receptor (19%) and was less potent in provoking a mitogenic response in Balb/C 3T3 fibroblasts (50% at doses 10-100 ng/ml). The data demonstrate the importance of correct disulfide arrangement in IGF-I for full biological activity. PMID- 1606977 TI - Color-coded duplex sonography in impotence: significance of different flow parameters in patients and controls. AB - The use of color-coded duplex sonography of the cavernous arteries in the assessment of arteriogenic impotence was evaluated in 70 consecutive men referred for erectile dysfunction. Controls were 16 of the men with an unequivocal nocturnal penile tumescence and rigidity. After intracavernous injection of prostaglandin E1, peak flow velocity was 26.8 +/- 12.5 cm/s in patients and 37.2 +/- 13.0 cm/s in controls (p less than 0.05). 50% of the patients, but none of the controls, had peak flow velocities of less than 20 cm/s in at least 1 cavernous artery. However, within the range of 20-40 cm/s, there was marked overlap between groups. The mean flow velocity and resistance index did not improve the discriminative value of peak flow velocity. Peak flow velocity after intracavernous injection of vasoactive drug enables the discrimination between impotent patients and controls. In a single patient, however, particularly one with a flow velocity of 20-40 cm/s, definition of arteriogenic impotence remains difficult. PMID- 1606978 TI - Independent evaluation of impotence by colour Doppler imaging and cavernosometry. AB - Colour Doppler imaging and cavernosometry are the optimal means for objective assessment of pharmacologically induced penile erections. 21 impotent patients were assessed by both methods independent of the information derived from the other modality. The diagnosis obtained was found to be immediately consistent in only 10 cases, 7 of which had venous leakage. 6 of the remaining 11 patients had a diagnosis of mixed arterial and venous disease in one or the other modality, but only arterial or venous disease alone in the other. The remaining 5 patients had completely inconsistent diagnoses. However, knowledge of the clinical picture and awareness of the pitfalls in the diagnostic procedures allows most of the discrepancies to be explained. Colour Doppler imaging is subject to operator error but allows selection of patients for cavernosography. PMID- 1606979 TI - Multiple tumors in the same kidney: incidence and therapeutic implications. AB - Conservative surgery is proposed by many authors for small kidney tumors. We reviewed retrospectively the pathology reports of 727 operated patients. In 257, tumor diameter was less than or equal to 5 cm, in 158 it was less than or equal to 4 cm, and in 78 it was less than or equal to 3 cm. The number of multiple tumors were 26 (10.1%), 17 (10.75%), and 10 (12.8%) respectively, which means that there is a 10% potential risk of leaving a tumor in situ in case of conservative surgery. There is no security size limit. These parameters have to be considered before proposing conservative surgery for small kidney tumors as a standard treatment. PMID- 1606980 TI - Treatment of localized prostatic carcinoma using the transrectal ultrasound guided transperineal implantation technique. AB - Treatment of localized prostate cancer by ultrasonically guided transperineal 125I implantation, in contrast to open 125I implantation, may allow for ideal distribution of the seeds and may therefore lead to better treatment results. 46 patients with localized prostatic carcinoma (T1-T2, G1-G3, N0, M0) have been treated since 1985, using this new technique. The longest follow-up is 64 months (median 30 months). The irradiation implantation dose to the prostate was 160 Gy. Assessed by ultrasonography an average prostate volume reduction of 20% was achieved at 6 months, increasing to 24% at 12 months, 39% at 24 months and 56% at 48 months. To evaluate response of the primary tumor systematic ultrasonically guided needle biopsies from the previous malignant prostate areas were performed in all patients every 6 months during follow-up. Tumor-negative biopsies were obtained in 33% of patients at 12 months, 40% at 24 months, progressively increasing to 50% at 48 months. Three patients developed distant metastases, and 6 died, of whom 1 patient due to prostate cancer. Morbidity from implantation has been low and the erectile function was preserved in all patients at 12 months postimplantation. The high percentage of tumor-positive biopsies during follow-up indicates that this technique fails to cure a significant proportion of patients. PMID- 1606982 TI - Etiology of acute scrotum at surgical exploration in children, adolescents and adults. AB - Between January 1970 and December 1989, 171 patients underwent scrotal exploration for acute scrotum (an acute painful swelling of the scrotum or its content), at our hospital. Of 70 children scrotal explorations, torsion of appendages was found in 33 cases (47%). Torsion of testis was found in 24 patients (34%). Of the 84 adolescent scrotal explorations performed, 72 (86%) had torsion of testis, and 8 (9%) had torsion of appendages. Of 17 adults, torsion of testis was found in 15 cases (88%). These results clarify that unnecessary explorations are much more common in children (66%) than in adolescents and adults (14%). We therefore suggest using radionuclear scans and/or Doppler ultrasound to facilitate clinical diagnosis in the children group. PMID- 1606981 TI - 4'-epidoxorubicin versus mitomycin C intravesical chemoprophylaxis of superficial bladder cancer. AB - The authors report the preliminary data concerning a phase III study comparing the chemoprophylactic effects of mitomycin C and epirubicin in Ta-T1 primary and recurrent superficial bladder tumors. 60 patients were treated, 32 with epirubicin and 28 with mitomycin C, with a medium follow-up of 17.7 and 16.2 months, respectively. There were no systemic side effects. The remission rate was 62.5% in the epirubicin group and 64.2% in the mitomycin C group. Both drugs were equally useful in the chemoprophylaxis of superficial bladder cancer. PMID- 1606983 TI - Study of the changes in collagen of the tunica albuginea in venogenic impotence and Peyronie's disease. AB - We identified the collagen type and content of the tunica albuginea in Peyronie's disease and venogenic impotence compared with the tunica albuginea from the donor of the renal transplant and patients with penile injury. Type III collagen was detected obviously in Peyronie's plaque and was also present in venogenic impotence. It can be hardly found in normal controls. The ratios of type III to type I collagen were significantly higher in Peyronie's plaque while there was a moderate increase in venogenic impotence. The scarcity of type V collagen was noted in human tunica albuginea. The decreased percentage of glycine and alanine in Peyronie's disease and venogenic impotence implied the abnormal composition of collagen or presence of noncollagen protein. The results suggest the biochemical aberration of the tunica albuginea might interfere with the normal function of the penile drainage system. PMID- 1606984 TI - Safety and immunoresponse study of intravesical instillation of Taipei-NIPM bacillus Calmette-Guerin. AB - The intravesical instillation of bacillus Calmette-Guerin (BCG) has proved to be an effective modality for prophylaxis of recurrent superficial bladder cancer and treatment of carcinoma in situ. The domestic BCG, named Taipei-NIPM, which is produced by the National Institute of Preventive Medicine, has been used as an anti-TBC vaccine in Taiwan for decades. In this study, we have investigated the safety and immune response in animals after intravesical BCG treatment to test its feasibility in future clinical application. Weekly instillation of BCG (1 mg/ml, 5-8 x 10(7) CFU/mg) for 6 instillations could induce lymphocytic infiltration, submucosal fibrosis, and granulomatous reaction after 4 weeks with mild decrease of bladder weight and high incidence of hematopyuria (75%). No changes in appetite, body weight, and splenic weight were noticed in the chronically treated rats. A delayed hypersensitivity test through foot pad swelling measurement reached 80% positive rates at 2 weeks. Cystometric study revealed a mild decrease in bladder capacity (33.3%) at 2 weeks and of contractile pressure of the urinary bladder in rats receiving BCG instillations. In addition, increase in lymphocytic infiltration by natural killer (NK) cells against YAC-1 cells could be detected after BCG treatment and this was related to dosage of BCG. The urothelial damage by cauterization and the number of instillations could also enhance NK cell activity. Low toxicity and high safety of intravesical instillation of the domestic BCG are demonstrated by this pilot animal study. This information on local and systemic immune responses can provide a solid base for future efficacy of BCG immunotherapy in bladder cancer patients using this domestic strain BCG. PMID- 1606985 TI - Study of cellular DNA content by flow cytometry in primary bladder carcinomas. Significance of monoclonal and multiclonal varieties of DNA aneuploidy. AB - A prospective study of cellular DNA content by flow cytometry was performed on a nonconsecutive series of 67 patients undergoing diagnostic and/or therapeutic transurethral resection for primary urothelial bladder carcinoma. DNA-aneuploidy was present in 82% of the cases (55/67), while multiclonality was found in 45% of the DNA-aneuploid cases (25/55). DNA-ploidy was much more strictly correlated with histological grading (p less than 0.005) than with papillary or non papillary growth pattern (p less than 0.05) or T staging (p less than 0.05). Of 26 patients with a minimum follow-up of 24 months, 100% (6/6) of cases with DNA diploid neoplasias showed no signs of disease relapse, versus 10% (2/20) of those with DNA-aneuploid neoplasias (p less than 0.001). Furthermore, tumoral progression occurred in 10 of 20 cases (50%) with aneuploid DNA content. In this latter group of 10 cases a multiclonal DNA-aneuploid pattern was found, with a significant difference (p less than 0.001). PMID- 1606986 TI - Healing of bladder wall after contact and non-contact Nd-YAG laser photocoagulation. Experimental study in piglets. AB - The healing process of the bladder wall after contact and non-contact Nd-YAG laser irradiation was studied in 18 piglets. The animals were sacrificed 1 h, and 2, 5 and 14 days after photocoagulation. The lesions were examined histologically by light and scanning electron microscopy. Immunohistochemical stains were prepared for visualization of lactate dehydrogenase. Perforation of the bladder wall was found in 2 cases where a contact probe was used (15 W/2 s). A crater in the bladder wall resulting from tissue ablation was seen in all cases immediately after contact laser irradiation. Photocoagulation using a non-contact laser led to white necrosis in the bladder wall. Minimal tissue ablation was evident at the highest power setting used (35 W/2 s). After 2 days inflammation around the lesion was marked. Inflammation with fibroblasts invading the damaged area was seen 5 days after photocoagulation. Fourteen days after photocoagulation minor scar formation was evident beneath the histologically normal epithelium. It is concluded that lesions caused by contact or non-contact Nd-YAG laser photocoagulation will heal within 2 weeks with minor scar formation. PMID- 1606987 TI - Expression of HLA class-I antigens on renal cell carcinoma and non-transformed renal tissue. AB - To determine the HLA class-I antigen expression in renal cell carcinoma, the expression of beta-2-microglobulin (beta 2-m) was analyzed. 20 renal tumor specimens and 20 normal renal tissues were examined for beta 2-m expression by immunofluorescence. Homogenous staining of all normal renal tissues was observed, as expected. From the panel of 20 tumors, 17 also had a strong expression of beta 2-m. Furthermore, two newly established renal cancer cell lines exhibited a normal distribution of beta 2-m at two different passages. From these results we conclude that in most cases malignant transformation in renal cancer is not associated with a loss of HLA class-I antigens. This could be a favorable explanation for the restricted results of interferon-gamma in renal cell carcinoma, the main function of which is probably to enhance major histocompatibility complex class-I expression. PMID- 1606988 TI - The role of sensory nerves in catheter-induced urethral inflammation. AB - We have studied the contribution of the nervous system on experimentally induced urethral inflammation in the rat. Urethral inflammation was produced by inserting latex strips into the urethra. The effects of different experimental procedures were assessed by using a 4-grade inflammation scale based on histological findings. Attenuation of urethral inflammation was produced by administration of capsaicin at birth. A more complete attenuation was produced by infusion of capsaicin prior to application of the latex strip. These data taken together indicate that sensory innervation of the urethral mucosa is involved in the inflammatory reaction and that infusion of the urethra with capsaicin may be tried to prevent catheter-induced urethral inflammation. PMID- 1606989 TI - Flow visualization in uroendoscopy: the steal effect. AB - Balanced continuous flow resection has been offered as the best form of irrigation in uroendoscopy. Although it will keep the bladder pressure low, using flow visualization techniques it has been demonstrated that it does not fulfil the requirements of an irrigating fluid when used in a confined environment such as the prostatic urethra. The outflowing irrigating fluid has been shown to be taken directly from the inflowing jet ('steal effect') thereby reducing the effectiveness of the irrigating jet on the working area of the resectoscope. PMID- 1606990 TI - Primary non-Hodgkin's lymphoma of the urinary bladder. AB - Primary non-Hodgkin's lymphoma of the bladder is a rare entity and when found in such an unusual location is often difficult to distinguish from other vesical or extravesical neoplasms. Understanding of the pathobiological characteristics of this malignancy has been hampered not only because of its rarity but also by the previous confusion in its nomenclature. Factors that influence survival most strongly are the stage and the bulk of disease at presentation and the histologic classification of the tumor. We report a case of primary non-Hodgkin's lymphoma of the bladder presenting as a large pelvic mass which dramatically regressed with systemic chemotherapy with simultaneous restoration of the upper dilated urinary tracts. In addition, the incidence, clinical picture, staging procedures, histologic classification and treatment modalities of this disease are reviewed. PMID- 1606991 TI - Disposition of antipyrine in patients with extensive metastatic liver disease. AB - In the present study the effect of metastatic liver disease on hepatic drug metabolism has been examined by studying the pharmacokinetics of antipyrine and the urinary excretion of antipyrine and its three major metabolites (4 hydroxyantipyrine, norantipyrine, and 3-hydroxymethylantipyrine) in 12 patients with extensive metastatic liver disease, and in 12 matched healthy controls. In the patients total liver volume, the volume of the liver parenchyma, and the volume of the liver metastases were determined by computed tomography. The volume of liver metastases always exceeded 35% of the total liver volume. There were no significant differences between the patients and controls in plasma half-life, plasma clearance, or apparent volume of distribution of antipyrine. The cumulative urinary excretion of antipyrine and its three major metabolites was significantly lower in patients [44 (18) %] than in controls [71 (8) %]. The excretion of antipyrine itself was unchanged and the decrease in cumulative excretion was due to reduced excretion of the three metabolites. The results show that the activity of the hepatic mixed function oxidases was not impaired even in patients with extensive metastatic liver disease. This may be because liver metastases do not cause a corresponding reduction in the volume of normal hepatic parenchyma. The decreased urinary excretion of the three major metabolites of antipyrine, which are mainly glucuronidated, may have been due to an alteration in the process of conjugation. PMID- 1606992 TI - Both phenolic and acyl glucuronidation pathways of diflunisal are impaired in liver cirrhosis. AB - The pharmacokinetics of diflunisal, a salicylate derivative that undergoes phenolic and acyl glucuronidation as well as sulphate conjugation, has been studied after a single oral dose (250 mg) in patients with cirrhosis (n = 5) and in healthy controls (n = 5). The plasma clearance of total (bound + unbound) diflunisal was 10.2 ml.min-1 in the control subjects and it was not affected by cirrhosis (10.9 ml.min-1). The plasma protein binding of diflunisal was significantly reduced in cirrhosis; the percentage of unbound diflunisal in plasma was 0.089 in the controls and 0.147 in the patients with cirrhosis. Plasma clearance of unbound diflunisal was significantly impaired in cirrhosis: 11.5 l.min-1 in control subjects vs 7.41.min-1 in cirrhotics. In cirrhotic patients, the unbound partial clearances to the phenolic and acyl glucuronides were both significantly reduced, by approximately 38%. The unbound partial clearance to the sulphate conjugate was not significantly affected by cirrhosis. The results show that both the phenolic and acyl glucuronidation pathways of diflunisal are equally susceptible to the effects of liver cirrhosis. PMID- 1606993 TI - Elevated plasma nilvadipine concentration after single and chronic oral administration to patients with chronic liver disease. AB - Fourteen normotensive patients with liver disease (6 with cirrhosis and 8 with chronic hepatitis) and 7 healthy volunteers were given a single oral dose of nilvadipine 2 mg. In addition, nilvadipine 4 mg was administered orally twice daily for several months to 6 hypertensive patients with mild liver dysfunction and 18 hypertensives with normal liver function. A significant increase in plasma nilvadipine was found in the patients with cirrhosis as compared both to the normal and chronic hepatitis subjects; the time to peak concentration was similar among the three groups. The peak plasma nilvadipine concentration was closely correlated both with the serum albumin level and the retention of indocyanine green. Changes in blood pressure, pulse rate and various vasoactive hormones following a single oral dose of nilvadipine did not differ between the groups. Thus, an increase in plasma nilvadipine relative to the level in normal subjects was demonstrated in patients with cirrhosis following a single oral dose, as well as in patients with slight liver dysfunction following long-term oral administration. PMID- 1606995 TI - The effects of alprazolam alone and combined with alcohol on central integrative activity. AB - The effects of alprazolam 1 mg both alone and in combination with 0.5 g/kg of alcohol were examined on self-ratings of intoxication and measures of central and peripheral activity such as EEG, auditory evoked response, tremor at 90, 150 and 210 min post drug. Forty-eight healthy volunteers were assigned randomly to 4 independent groups who received: alprazolam and placebo drink, alprazolam and alcohol, placebo capsule and alcohol, placebo capsule and placebo drink respectively. Alprazolam decreased the amplitudes of the 3 potentials of the evoked response, decreased activity in the 8-13 Hz and increased activity in the 13.5-26 Hz wavebands of the EEG and decreased the frequency at which fusion was perceived. Alcohol prolonged reaction time and increased tremor. The effects were not always additive and alprazolam was dominant in the combination. PMID- 1606994 TI - Digoxin-interactions in man: spironolactone reduces renal but not biliary digoxin clearance. AB - The possibility of an inhibitory effect of spironolactone on the biliary clearance of digoxin has been investigated in 6 healthy subjects. Plasma clearance and the renal and biliary clearance of digoxin were determined twice at steady state (digoxin 0.5 to 1 mg.d-1 p.o. for 6 days), alone or in combination with spironolactone 200 mg daily, after an intravenous dose of digoxin (0.7 x oral dose) on Day 7. Plasma and urine were collected for 48 h. Biliary clearance of digoxin was determined on Day 8 by a duodenal perfusion technique. During spironolactone treatment plasma digoxin clearance tended to be lower (255 vs 224 ml/min; P = 0.057) and renal clearance significantly lower (166 vs 144 ml/min), while the biliary clearance of digoxin remained unchanged (106 vs 103 ml/min). Thus, spironolactone reduced the renal clearance of digoxin by an average of 13%, without affecting its biliary clearance. PMID- 1606996 TI - Correlation between doses of oxazepam and their effects on performance of a standardised test battery. AB - Ten different doses of oxazepam (ranging from 7.5 to 50 mg) or placebo were administered to a total of 28 female subjects in three separate studies. Subjects completed a battery of psychometric tests at 1 and 2 h postdose. The tests included critical flicker fusion, choice reaction time and a tracking task. Following separate analyses of variance, effect sizes (Cohen's d) were calculated for each dose at each dependent variable. These effect sizes were then correlated with the dose of drug administered, using regression analyses. It was found that the doses correlated highly with most of the psychometric variables determined, implying that the test battery is sensitive to drug effects. PMID- 1606997 TI - The use of drugs in Estonia compared to the Nordic countries. AB - Wholesale data from Estonia covering all drug supplies during the period 1983 1989 have been studied using the defined daily dose (DDD) methodology. The use of all major pharmacological groups was compared with the corresponding statistics from the Nordic countries. The patterns of drug use showed large differences between the Nordic countries and Estonia. Many drugs were used in large quantities in Estonia although they are no longer considered to be first-line medications in the Nordic countries because of their high risk to benefit ratio. These included the pyrazolones (phenylbutazone, aminophenazone), chloramphenicol, aminoglycoside antibiotics, and Rauwolfia alkaloids. On the other hand, several groups of effective drugs were available in Estonia only in limited amounts, including the histamine (H2) receptor antagonists, hormonal contraceptives, beta adrenoceptor antagonists, angiotensin converting enzyme inhibitors, and cephalosporins. There were also differences in the use of non-steroidal anti inflammatory drugs, blood pressure lowering agents, and anti-asthmatic drugs. Amongst the factors influencing drug usage it appears that economic status, the ordering and invoicing routines of the pharmaceutical services, and therapeutic traditions were the main reasons for the differences found. PMID- 1606998 TI - Adverse event monitoring in clinical trials of felodipine and omeprazole. AB - Although most clinical trials encompass aspects of safety, methods for assessing the safety of a drug by recording adverse events have been poorly studied. It has been suggested that adverse events rather than adverse drug reactions should be monitored, since a reliable determination of which events were caused by the drug and which were not is only possible after analysing data from a substantial number of clinical trials. In the present study adverse events were monitored to see the extent to which events recorded on the case record forms were reported as adverse events. Data from omeprazole and felodipine programmes were used, comprising altogether 143 clinical trials from eight different projects, and encompassing 12,069 patients in whom 11,812 events were recorded. The first project was started in 1982 and the last in 1988. Overall, 74% of recorded events were entered on a special adverse event form used in the trials, and 26% were not. Initially, about 35% of adverse events were not reported as such, as opposed to 13% towards the end of the study period. Serious adverse events were reported less frequently than non-serious events, but in the most recent project all serious adverse events were reported. Adverse events in women were reported more often than adverse events in men, and reporting was more complete for the middle aged than for the oldest and the youngest persons. Certain types of adverse events were reported more completely than others. In conclusion, the transition from registering adverse reactions to registering adverse events has been a gradual one in spite of intensive educational efforts when the projects were started.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1606999 TI - A comparison of the effects of fluvoxamine and amitriptyline on autonomic functions in healthy volunteers. AB - We have compared the effects of single oral doses of fluvoxamine (50 mg and 100 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced, double-blind, crossover design. Amitriptyline significantly reduced salivation, the miosis evoked by locally applied pilocarpine, and the sweat secretion evoked by locally applied carbachol. Fluvoxamine also significantly attenuated carbachol-evoked sweat gland activity, although to a smaller degree than amitriptyline; fluvoxamine did not significantly alter salivation or pilocarpine-evoked miosis. Neither treatment significantly altered the miotic responses evoked by brief light stimuli. Heart rate and blood pressure were not greatly affected by either treatment, although the fall in heart rate (erect posture) with placebo was significantly reduced by amitriptyline (100 mg). The results suggest that fluvoxamine has some anti muscarinic activity in man, but is considerably less potent in this respect than amitriptyline. PMID- 1607000 TI - Pharmacokinetics of meropenem in subjects with renal insufficiency. AB - The pharmacokinetics of IV meropenem (500 mg over 30 min) has been studied in 6 healthy volunteers and 26 patients with various degrees of renal impairment. Blood samples were taken at different times over 24 h in healthy subjects and 36 to 48 h in uraemic patients, and four or five urine samples were collected over 24 or 48 h. Meropenem concentrations in plasma and urine were measured by a microbiological assay. The mean peak plasma concentration of meropenem ranged from 28 to 40 micrograms.ml-1 and was not affected by the degree of renal impairment. The terminal half-life of meropenem was approximately 1 h in subjects with normal kidney function and it was proportionately increased as renal function decreased. A significant linear relationship between total body clearance and creatinine clearance as well as between renal clearance and creatinine clearance was observed. The mean apparent volume of distribution at steady state was not significantly altered in uraemic patients. The mean cumulative urinary recovery of meropenem in healthy volunteers was 77% of the administered dose and it was significantly decreased in patients with renal impairment. Haemodialysis shortened the elimination half-life, from 9.7 h during the predialysis period to 1.4 h during the dialysis period. The dose of meropenem should be reduced in relation to the decrease in creatinine clearance. PMID- 1607001 TI - Stereoselective pharmacokinetics of doxepin isomers. AB - Commercial preparations of the tricyclic anti-depressant doxepin contain 15% of the more active cis-doxepin and 85% of the trans-isomer. The single dose pharmacokinetics of doxepin and its major metabolite N-desmethyldoxepin were examined in 30 healthy young men. Results for total doxepin showed wide intersubject variation in all pharmacokinetic parameters except tmax and Cmax. Plasma levels of cis-doxepin were extremely low and it was only possible to estimate the stereoselective pharmacokinetics of the parent drug in 3 subjects. The data from those particular subjects resulted in an average ratio of cis- to trans-doxepin isomers in plasma of 15:85. In contrast, the mean plasma levels of cis-N-desmethyldoxepin in 28 subjects exceeded those of the trans-isomer at every time point after 10 h, such that the areas under the plasma concentration versus time curves (AUC) of cis-N-desmethyldoxepin were significantly higher than those of the corresponding trans-isomer. This phenomenon may play an important role in the therapeutic action of doxepin since it has been suggested that cis-N desmethyldoxepin is pharmacologically active. In 2 subjects, however, the AUC0 inf of trans-N-desmethyldoxepin were respectively 4 and 8 fold higher than those of the cis-isomer. PMID- 1607002 TI - Pharmacokinetics of vinorelbine in man. AB - The pharmacokinetics of vinorelbine has been investigated by a new HPLC method in 8 cancer patients receiving 8 weekly doses (30 mg.m-2) administered by brief infusion (15 min). The plasma concentration-time curves showed a tri-exponential decay with a long terminal half-life (44.7 h) and a high volume of distribution (Vz = 75.61.kg-1). The concentrations after the 8th infusion were significantly lower than after the 1st infusion, but without significant modification of CL (1.28 l.h-1.kg-1) or AUC (0.80 mg.l-1.h). The pharmacokinetic parameters exhibited wide interindividual variations. The results are consistent with those of previous RIA studies, although the HPLC method appears to be more specific and more precise. PMID- 1607004 TI - Pharmacokinetics of mefloquine in the presence of primaquine. PMID- 1607003 TI - Investigation of a possible pharmacokinetic interaction between ibopamine and isosorbide-5-mononitrate. AB - The possibility of a pharmacokinetic interaction between isosorbide-5-mononitrate (5-ISMN) and epinine, the active metabolite of ibopamine, has been investigated in 8 healthy male subjects given single doses of 200 mg ibopamine and 20 mg 5 ISMN, separately and together. The plasma 5-ISMN concentration-time profile was the same whether 5-ISMN was administered concomitantly with ibopamine or alone [AUC(o-t): 2.24 micrograms.ml-1.h after 5-ISMN alone, 2.16 micrograms.ml-1.h after 5-ISMN+ibopamine]. The plasma concentrations of total and free epinine and the urinary recovery of total epinine, homovanillic acid and dihydroxyphenylacetic acid, too, were not different when ibopamine was administered alone or concomitantly with 5-ISMN. The intake of ibopamine did not change the blood pressure and heart rate. The decrease in diastolic blood pressure induced by 5-ISMN was not influenced by concomitant intake of ibopamine. The observations suggest that in healthy volunteers there is no pharmacokinetic interaction between 5-ISMN and ibopamine. PMID- 1607005 TI - Stereochemistry of oxidized fatty acids generated during catalytic oxygenation of lauric acid and unsaturated analogs by plant microsomes. AB - The capacity of microsomes from aminopyrine-induced Jerusalem artichoke (Helianthus tuberosus L.) to oxidize saturated and unsaturated fatty acids has been investigated using lauric acid and a series of unsaturated lauric acid analogs (7-, 8-, 9- and 10-dodecenoic acids) as radiolabeled substrates. In the presence of NADH, lauric acid was mono-hydroxylated principally at carbon 9. Steric analysis of this product showed a low enantiomeric excess of 28%. Mono hydroxylated and mono-epoxidated reaction products were formed from the unsaturated analogs. The epoxidation/hydroxylation ratio was related to the position of the double bond in the aliphatic chain. The oxidation of 7-dodecenoic acid (7-DDNA) and 10-DDNA produced mainly 9-hydroxy-7-DDNA and 9-hydroxy-10-DDNA plus minor amounts of 7,8-epoxy- or 10,11-epoxylauric acid, respectively. In contrast, 8- and 9-DDNAs yielded essentially 8,9-epoxy- and 9,10-epoxylauric acids and smaller amounts of 10-hydroxy-9-DDNA and 8-hydroxy-9-DDNA, respectively. The optical purity and the absolute configuration of the major metabolites were investigated. Epoxidation of Z 8-DDNA and Z 9-DDNA occurs with high enantiomeric excesses. When the double bond was in the Z configuration, (8S,9R)/(8R,9S) 8,9-epoxylauric acid (93/7) or (9R,10S)/(9S,10R) 9,10-epoxylauric acid (89/11) were produced. In contrast, when the double bond was in the E configuration, steric analysis showed an enantiomeric ratio of 52/48 for E 8,9 epoxide and of 59/41 for E 9,10-epoxide. Z 7-DDNA led to the formation of 98% of the 9(S)-hydroxy-Z 7-DDNA enantiomer, while 9-hydroxy-Z 10-DDNA derived from Z 10 DDNA was 35% (R) and 65% (S). PMID- 1607006 TI - Targeting signal of the peroxisomal catalase in the methylotrophic yeast Hansenula polymorpha. AB - The methylotrophic yeast, Hansenula polymorpha, harbours a unique catalase (EC 1.11.1.6), which is essential for growth on methanol as a carbon source and is located in peroxisomes. Its corresponding gene has been cloned and the nucleotide sequence determined. The deduced amino acid sequence displayed the tripeptide serine-lysine-isoleucine at the extreme C-terminus, which is similar to sequences of other peroxisomal targeting signals. Exchange of the ultimate amino acid, isoleucine, of catalase for serine revealed a cytosolic enzyme activity and a concomitant loss of peroxisome function. We concluded that the tripeptide is essential for targeting of catalase in H. polymorpha. PMID- 1607007 TI - Demonstration of DNA binding factors interacting with a fragment of the canine prostate arginine esterase gene promoter. AB - We have studied, by the gel mobility shift assay, the interaction of DNA binding proteins with a fragment of the proximal promoter (from nucleotides -177 to -47) of the androgen-regulated canine prostate arginine esterase gene. Several shifted bands were obtained using nuclear extracts from various tissues. In the case of the prostate, the intensity of some of the shifted bands was decreased or increased when the extracts were prepared from animals that had been castrated 12 days earlier. Several of the DNA-protein complexes could be assigned to an interaction with part or all of the sequence GGGGGTGGGGG from-124 to -114. We also obtained evidence for the presence of protein(s) interacting with an Sp1 motif present in the same fragment. These results suggest that some ubiquitous factors different from the androgen receptors could be involved in the regulation of the arginine esterase gene. PMID- 1607008 TI - Dynamic aspects of ovarian superoxide dismutase isozymes during the ovulatory process in the rat. AB - To investigate the role of superoxide dismutase (SOD) in the ovulatory process, SOD isozymes and their mRNAs were determined in the ovary of 22-day-old rats. After treatment with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG), ovarian activity of Mn-SOD decreased markedly while Cu/Zn-SOD remained unchanged. However, the ovarian level of mRNA for Mn-SOD markedly increased after hCG-treatment while that for Cu/Zn-SOD decreased only slightly. Ovulation was inhibited by intravenous injection of a long-acting SOD. These results suggested that superoxide radicals in the ovary might play a critical role in the mechanism for hCG-induced ovulation. PMID- 1607009 TI - The fibrillar collagens, collagen VIII, collagen X and the C1q complement proteins share a similar domain in their C-terminal non-collagenous regions. AB - A sequence comparison of the C-termini of collagens X, VIII, the collagen-like complement factor C1q, and the fibrillar collagens showed a conserved cluster of aromatic residues. This conserved cluster was in a domain of approximately 130 amino acids that exhibited marked similarities in hydrophilicity profiles between the different collagens, despite a low level of sequence similarity. These data suggest that the 'collagen X-like family' and the fibrillar collagens contain a domain within their C-termini that adopts a common tertiary structure, and that a conserved cluster of aromatic residues in this domain may be involved in C terminal trimerization. PMID- 1607010 TI - 1H, 15N and 13C NMR assignments of the 434 repressor fragments 1-63 and 44-63 unfolded in 7 M urea. AB - An E. coli overexpression system for the N-terminal domain of the 434 repressor with residues 1-63 (434 repressor(1-63)) was constructed and used to produce this polypeptide with uniform 15N-labeling, and with 13C-labeling of the methyl groups of valine and leucine. Using these protein preparations almost complete sequence specific resonance assignments were obtained for the urea-unfolded form of the 434 repressor(1-63). In addition, the isotope-labeled tryptic peptide, 44-63, was produced by enzymatic cleavage of the recombinant 434 repressor(1-63), and its NMR spectrum was assigned. Corresponding residues in 434 repressor(1-63) and 434 repressor(44-63) in 7 M urea were found to have nearly identical chemical shifts, and in both species similar deviations from 1H random coil shifts were found as previously in 434 repressor(1-69). These indicate the presence of residual non random structure in the polypeptide segment 50-60. The present NMR assignments, which include stereospecific assignments for the diastereotopic methyl groups of Val and Leu, are the basis for detailed studies of this residual structure in the urea-unfolded form of the 434 repressor. PMID- 1607011 TI - 15N NMR assignments and chemical shift analysis of uniformly labeled 15N calbindin D9k in the apo, (Cd2+)1 and (Ca2+)2 states. AB - 15N has been uniformly incorporated into the EF-hand Ca(2+)-binding protein calbindin D9k so that heteronuclear experiments can be used to further characterize the structure and dynamics of the apo, (Cd2+)1 and (Ca2+)2 states of the protein. The 15N NMR resonances were assigned by 2D 15N-resolved 1H experiments, which also allowed the identification of a number of sequential and medium-range 1H-1H contacts that are obscured by chemical shift degeneracy in homonuclear experiments. The 15N chemical shifts are analyzed with respect to correlations with protein secondary structure. In addition, the changes in 15N chemical shift found for the apo----(Cd2+)1----(Ca2+)2 binding sequence confirm that the effects on the protein are mainly associated with chelation of the first ion. PMID- 1607012 TI - The amino acid composition is different between the cytoplasmic and extracellular sides in membrane proteins. AB - The amino acid composition of transmembrane proteins was analyzed for their three separate portions: the transmembrane apolar, cytoplasmic and extracellular regions. The composition was different between cytoplasmic and extracellular peptides: alanine and arginine residues were preferentially sited on the cytoplasmic side, while the threonine and cysteine/cystine were preferentially sited on the extracellular side. The composition of cytoplasmic and extracellular peptides of membrane proteins corresponded to those of intracellular and extracellular types of soluble proteins, respectively. This difference in composition was independent of the peptide orientation against the membrane. Peptide chains could be correctly assigned as either cytoplasmic or extracellular, solely from an analysis of sequence composition. For single spanning membrane proteins the predictive accuracy was 90%, whereas for multi spanning proteins this was 85%. PMID- 1607013 TI - The interaction between ruptured erythrocytes and low-density lipoproteins. AB - Low-density lipoproteins (LDL) are oxidatively modified on interaction with haem proteins. The interaction of ruptured erythrocytes with LDL induces oxidative damage as detected by alterations in electrophoretic mobility and the peroxidation of the polyunsaturated fatty acyl chains. Difference spectroscopy reveals that the amplification of the oxidative process by the haem protein is related to the transition of the oxidation state of the haemoglobin in the erythrocyte lysate from the oxy [X-FeII-O2] to the ferryl [X-FeIV = O] form. The incorporation of the lipid-soluble antioxidant, butylated hydroxy toluene, at specific time points during the LDL-erythrocyte interaction prolongs the lag phase to oxidation and eliminates the oxy-to-ferryl conversion of the haemoglobin. The timescale of this haem conversion is related to the antioxidant status of the LDL. PMID- 1607014 TI - Cyanobacterial metallothionein gene expressed in Escherichia coli. Metal-binding properties of the expressed protein. AB - The recently isolated Synechococcus gene smtA encodes the only characterised prokaryotic protein designated to be a metallothionein (MT). To examine the metal binding properties of its product the smtA gene was expressed in Escherichia coli as a carboxyterminal extension of glutathione-S-transferase. The pH of half dissociation of Zn, Cd and Cu ions from the expressed protein was determined to be 4.10, 3.50, 2.35, respectively, indicating a high affinity for these ions (in particular for Zn in comparison to mammalian MT). E. coli expressing this gene showed enhanced (ca. 3-fold) accumulation of Zn. PMID- 1607016 TI - The uptake and expression of the factor VIII and reporter genes by vascular cells. AB - The conditions and efficacy of transfection of vascular cells in primary culture using DEAE-dextran, calcium phosphate and lipofectin have been investigated using chloramphenicol acetyltransferase and luciferase as reporter genes. Subsequently factor VIII was expressed in endothelial and smooth muscle cells. Both reporter genes could be expressed after transfection of umbilical vein endothelial cells, umbilical artery smooth muscle cells and fibroblasts. The expression of both reporter genes in endothelial and smooth muscle cells was highest using lipofectin. After transfection of smooth muscle cells with both full-length and mutant factor VIII genes, factor VIII activity and antigen were secreted into the culture medium, the secretion remaining stable to serial cell passage. The secretion of factor VIII from transfected smooth muscle cells was confirmed by the immunoprecipitation of [35S]methionine labelled protein. Endothelial cells also were successfully transfected with the mutant factor VIII gene. PMID- 1607015 TI - The 5' untranslated region from pea seedborne mosaic potyvirus RNA as a translational enhancer in pea and tobacco protoplasts. AB - We have exploited the transient expression of foreign genes introduced into plant protoplasts to investigate the effect of the pea seedborne mosaic potyvirus (PSbMV) 5' untranslated region (5'UTR) on the level of gene expression in pea and tobacco protoplasts. The plant viral 5'UTRs were found to increase translation significantly in comparison to a plasmid containing no 5'UTR of viral origin. The enhancement effect of the 5'UTRs of PSbMV and tobacco etch potyvirus (TEV) was found to be similar in pea and tobacco protoplasts, indicating a host-independent role of the potyviral 5'UTRs in enhancing gene expression. Translational enhancement of the two potyviral 5'UTRs was similar to that of the 5'UTR of tobacco mosaic virus (TMV). This observation makes it attractive to use potyviral 5'UTRs as general translational enhancers in future genetic transformations of plants. PMID- 1607017 TI - Mapping and sequencing of an actively transcribed Euglena gracilis chloroplast gene (ccsA) homologous to the Arabidopsis thaliana nuclear gene cs(ch-42). AB - We mapped and sequenced a novel chloroplast gene encoding a protein (348 amino acids) which shows a high sequence identity with both the decoded nuclear cs(ch 42) gene product of Arabidopsis thaliana, and the C-terminal half of the decoded 'crtA' gene product of Rhodobacter capsulatus. The chloroplast gene (ccsA) is split (two exons) and transcribed into a stable mRNA of about 1200 nucleotides. The putative protein may be involved in the biosynthesis of photosynthetic pigments. PMID- 1607018 TI - Anion permeation limits the uncoupling activity of fatty acids in mitochondria. AB - The action of such membrane-permeant cations as tetraphenyl phosphonium and dibenzyldimethyl ammonium upon fatty acid-uncoupled respiration has been studied with oligomycin-inhibited rat liver mitochondria. Both cations enhance fatty acid stimulated respiration. This synergistic effect is explained by a facilitated permeation of the fatty acid anion across the inner membrane due to an ion-pair complex. It is concluded that fatty acid uncoupling in rat liver mitochondria is limited by fatty acid anion permeation. PMID- 1607019 TI - Inhibition of pigeon breast muscle alpha-ketoglutarate dehydrogenase by phosphonate analogues of alpha-ketoglutarate. AB - Succinylphosphonate (SP) is a powerful inhibitor of alpha-ketoglutarate dehydrogenase (KGD). Methylation of the phosphonate reduces its inhibitory effect. The complex of KGD with SP undergoes a kinetically slow transition similar to the process observed during catalysis. alpha-Ketoglutarate binds to the enzyme-inhibitor complex, preventing its isomerisation. PMID- 1607020 TI - Studies on the proteins involved in the interaction of high-density lipoprotein with isolated human small intestine epithelial cells. AB - Treatment of 125I-labelled high-density lipoprotein ([125I]HDL3) with monospecific polyclonal antibodies against apolipoproteins A-I and A-II resulted in a dose-dependent inhibition of the [125I]HDL3 binding to isolated human small intestine epithelial cells by 25% and 50%, respectively. Both antibodies also inhibited intracellular degradation of [125I]HDL3 by 80%. Treatment of enterocytes with polyclonal antibody against apolipoprotein A-I binding protein, a putative HDL receptor, inhibited both binding and degradation of [125I]HDL3 by these cells by 50%. Antibodies to apolipoprotein A-I, A-II and apo A-I-binding protein also inhibited [125I]HDL3 binding to cholesterol-loaded cells. PMID- 1607022 TI - Cytosolic chloride ions stimulate Ca(2+)-induced exocytosis in melanotrophs. AB - We used the whole-cell patch-clamp technique to study the secretory activity of single cells by monitoring changes in membrane capacitance [Neher, E. and Marty, A. (1982) Proc. Natl. Acad. Sci. USA 79, 523-535] in anterior pituitary cells. Unexpectedly we have observed that increasing intracellular chloride ions stimulate Ca(2+)-induced exocytosis in a dose-dependent fashion (Kd = 12 mM). These results demonstrate a role of cytosolic chloride ions in the regulation of exocytotic secretion in anterior pituitary cells. It is suggest that chloride channels, in addition to playing a part in regulating membrane electrical activity [Korn, S.J., Bolden, A. and Horn, A. (1991) J. Physiol. 439, 423-437; Penner, R., Matthews, G. and Horn, A. (1988) Nature 334, 499-504] and cytosolic pH [Kaila, K. and Voipio, J. (1987) Nature 330, 163-165], are also involved in the modulation of cytosolic chloride concentration and thus in the control of exocytosis. PMID- 1607021 TI - Contraction of guinea pig lung parenchyma by pancreatic type phospholipase A2 via its specific binding site. AB - Porcine pancreatic group I phospholipase A2 (PLA2-I) induced contraction of guinea pig parenchyma in a concentration-dependent manner. Its EC50 value was similar to the Kd value calculated from the specific binding of 125I-labeled porcine PLA2-I in the membrane fraction of guinea pig lung. Type-specific action of PLA2's and homologous desensitization strongly implicated the involvement of PLA2-I-specific sites in the activation process. Thromboxane A2 was found to be the main product from lung tissue by PLA2-I action and the contractile response by PLA2-I was specifically suppressed by thromboxane A2 receptor antagonists and cyclooxygenase inhibitor, but not by leukotriene receptor antagonist and H1 blocker. These findings indicate that PLA2-I-induced contractile response may depend on the secondarily produced thromboxane A2, thus providing a new aspect of PLA2-I from the pathophysiological standpoint. PMID- 1607023 TI - Regulation of a major cloned voltage-gated K+ channel from human T lymphocytes. AB - When expressed into Xenopus oocytes, HLK3 K+ channel (Kv1-3) induced a slowly inactivating voltage-dependent K+ current. We have studied the modulation of this K+ current by co-expressing a cloned 5-HT2 receptor together with HLK3 K+ channel protein. Application of 5-HT caused a long-lasting inhibition of the voltage gated K+ current. This inhibitory modulation was mimicked by intracellular injection of inositol triphosphate or Ca2+, as well as by incubation with phorbol esters or diacylglycerol analogs. Oocytes pretreatment with staurosporine and EGTA fully prevented 5-HT inhibitory action. Elevation of cAMP and cGMP levels into oocytes did not produce any detectable effect on the current recorded in the absence or the presence of 5-HT. These data suggest that the second messengers generated by phospholipase C activation may be important modulators of HLK3 K+ channels in the immune and the central nervous systems. PMID- 1607024 TI - Direct observation of lactate and alanine by proton double quantum spectroscopy in rat hearts supplied with [3-13C]pyruvate. AB - The 13C-fractional enrichments in the lactate and alanine methyl carbon positions were determined by 1H NMR spectroscopy of extracts of rat hearts perfused with various concentrations of [3-13C]pyruvate +/- unlabeled glucose or acetate. In general, the 13C-fractional enrichment of the alanine methyl carbon pool paralleled the 13C-fractional enrichment of the acetyl-CoA which entered the TCA cycle (as determined by 13C-isotopomer analysis) while the 13C-fractional enrichment of the lactate methyl carbon was always significantly lower, consistent with a pool of lactate which does not mix with exogeneous [3 13C]pyruvate. This has also been examined in intact, perfused, KCl-arrested rat hearts supplied with [3-13C]pyruvate by proton double quantum metabolite specific spectroscopy (MSS). A comparison of MSS spectra of intact hearts with one pulse spectra of extracts of those same hearts indicates there is a sizeable non enriched pool of lactate in the intact hearts which is not visible by NMR spectroscopy. PMID- 1607025 TI - Fusion of Mycoplasma fermentans strain incognitus with T-lymphocytes. AB - The ability of Mycoplasma fermentans (strain incognitus) to fuse with cultured lymphocytes was investigated and the fusion process was characterized. Fusion was measured using an assay to determine lipid mixing based on the dequenching of the fluorescent probe, octadecylrhodamine (R18), that was incorporated into the mycoplasma cells. Fusion of M. fermentans was detected with both CD4+ (Molt 3) and CD4- (12-E1) cells. The amount of fusion induced was relatively low and ranged from 5-10% with either cell culture. When primary peripheral blood lymphocytes were used the fusion yield was somewhat higher, reaching 12% of the cell population. Similar findings were obtained with fluorescent microscopy analysis suggesting that a predetermined, but unidentified subpopulation of cultured lymphocytes, were being fused. The rate of fusion was temperature dependent. Following a short lag period fusion at 37 degrees C was virtually completed in 60 min. The lymphocytes remained intact throughout the fusion process, as determined by the Trypan blue staining procedure. Fusion was almost completely inhibited by anti-M. fermentans antisera and by pretreatment of M. fermentans cells with proteolytic enzymes, suggesting that a surface-exposed proteinaceous component is involved in the fusion process. PMID- 1607026 TI - Thermal denaturation of the alkali light chain-20 kDa fragment complex obtained from myosin subfragment 1. AB - The thermal denaturation of the myosin subfragment 1 (S1) from rabbit skeletal muscle and of its derivatives obtained by tryptic digestion has been studied by means of differential scanning calorimetry. Two distinct thermal transitions were revealed in the isolated complex of the C-terminal 20 kDa fragment of the S1 heavy chain with the alkali light chain. These transitions were identified by means of a thermal gel analysis method. It has been shown that the thermal denaturation of the 20 kDa fragment of the S1 heavy chain correlates with the melting of the most thermostable domain in the S1 molecule. It is concluded that this domain is located in the C-terminal 20 kDa segment of the S1 heavy chain. PMID- 1607027 TI - Affinity modification of human chromatin with reactive derivatives of oligonucleotides. AB - Reaction of 4-(N-2-chloroethyl-N-methylamino)benzylphosphamides of oligonucleotides (RCl-(pT)16 and RCl-(pApC)6) with human chromatin in intact nuclei and with metaphase chromosomes has been investigated. The oligonucleotides were targeted to poly(A) and poly(TG)-repeating DNA sequences. It was found that the reagents alkylate DNA and some proteins due to specific complex formation. The affinity character of the reaction was proved by the fact that free corresponding oligonucleotides taken in excess or preliminary treatment of chromatin with S1-nuclease both prevent the biopolymers from modification. The results obtained evidence that in human chromatin there are open DNA sequences available for affinity modification with oligonucleotide derivatives. Analysis of patterns of modified proteins within these chromatin areas may give a key to the structure of these chromatin sites. PMID- 1607028 TI - Conservative surgery: achievements, risks and limitations. PMID- 1607029 TI - Locally recurrent breast cancer after 'radical' surgery. AB - Tumor recurrence at the site of radical surgery for mammary carcinoma has been studied in 101 cases. Analysis revealed the proximate causes--tumour size, axillary node metastases--and the more extensive type of surgery have a positive correlation even if the P values do not reach the significant value. The prognosis suggests that clinically this phenomenon, seen in the long term, does not differ from that of distant skin and subcutaneous metastases. A treatment strategy is proposed. PMID- 1607030 TI - The preservation of minor pectoralis muscle in axillary dissection for breast cancer: functional and cosmetic evaluation. AB - We have evaluated, in two groups of 50 patients each submitted to axillary dissection for breast cancer (10 mastectomies and 90 conservative procedures), the advantage of the preservation of the minor pectoralis muscle. This muscle was preserved in one group and removed in the other. Whereas in the immediate postoperative period complications (shoulder pain, functional impairment, quantity or duration of serum drainage from the axilla) were the same in the two groups, at longer follow-up (more than 6 months after surgery) the patients whose pectoralis minor muscle was preserved showed a reduction in the incidence of partial atrophy and fibrosis of the pectoralis major muscle. Patients treated with conservation of the pectoralis minor muscle showed this atrophy in 6% of cases vs 54% observed in the other patients. This fact may be related to disruption of the pectoral nerves, which are in close contact with the pectoralis minor during their course from the brachial plexus to the pectoralis major muscle. PMID- 1607031 TI - Advanced breast cancer in Egyptian women: clinical features and response to endocrine therapy. The Anglo-Egyptian Health Agreement Collaborative Study. AB - Response to endocrine therapy and its relationship to the clinical features of the disease were studied in 84 Egyptian patients with inoperable, locally advanced or metastatic breast cancer. Twenty-four premenopausal patients were treated by oophorectomy with or without concurrent prednisolone. Only one of 20 evaluable patients achieved an objective response. Median time to progression for premenopausal patients was 3 months. Sixty postmenopausal patients received tamoxifen 10 mg twice daily either alone or with prednisolone. Fourteen of 57 (25%) evaluable patients achieved an objective response (four complete remission, 10 partial remission). Median duration of response was 13 months and median time to progression for all postmenopausal patients was 5 months (range 1-30 months). The outcome for postmenopausal patients was similar to that found in a parallel study at Guy's Hospital, London. The response rate for premenopausal Egyptian patients was, however, disappointing and lends support to the claim that breast cancer in Egyptian women is particularly aggressive. PMID- 1607032 TI - Ki67 immunoreactivity in breast carcinoma: relationships to prognostic variables and short term survival. AB - Immunoreactivity of the monoclonal antibody Ki67, which recognizes an antigen expressed in cells active in the cell cycle, has been investigated by immunocytochemistry in a series of 67 primary breast cancers. The percentage of tumour cell nuclei stained by Ki67 (labelling index) was related to tumour histological grade, mitotic frequency, oestrogen receptor status and tumour type. No correlation was found with patient age, tumour size or lymph node stage. A high Ki67 labelling index was significantly associated with diminished patient survival and disease-free interval, which demonstrates an important role for this monoclonal antibody as a prognostic marker in breast cancer. PMID- 1607033 TI - An evaluation of the usefulness of primary tumour expression of MCA and CA15-3 as prognostic indicators in breast carcinoma. AB - CA15-3 antigen and mucin-like carcinoma associated antigen (MCA) show potential as clinically useful serum markers of breast carcinoma. Recently, immunohistochemical versions of these monoclonal antibodies have become available but few data are available as to their clinical usefulness. The aims of this study were (i) to assess CA15-3 and MCA expression by primary breast tumours and to correlate tumour immunoreactivity with tumour behaviour, and (ii) to investigate the relationship between immunohistological staining and oestrogen receptor (ER) status. Pathological material from 39 stage 1 (node free) breast carcinoma patients was assessed. The mean age was 51.3 (range 34-70) years, 19 were premenopausal and the mean duration of follow-up was 3.6 years (range 0.8-14 years). In each case two further sections were stained with antisera to the CA15 3 and MCA antigens. Staining of primary tumour was achieved in 38 cases. Low (less than 30% tumour cell staining) and intermediate (30-60% of cells staining) grade immunoreactivity with both monoclonals correlated with significantly shorter disease free intervals (P less than 0.05). Neither monoclonal can predict ER status. We conclude that the use of monoclonal antibodies to CA15-3 and MCA in staining primary breast carcinoma tumours and their axillary nodes may be a significant (P less than 0.05) prognostic indicator of future tumour behaviour and that this requires further evaluation. PMID- 1607034 TI - Hormone receptors, ploidy and proliferation rate in breast cancers up to 10 mm. AB - A total of 191 malignant mammary lesions of 10 mm or less in diameter have been analysed with regard to hormone receptor content (107 of 179) and ploidy (112 of 191) in a repeated mammography screening population (second to fourth screening round). Forty-eight per cent were diploid and 68% oestrogen receptor-positive. Mean proliferation rate, calculated as S-phase fraction (SPF), was 6.2 +/- 5.0. Significantly lower SPF was observed in diploid tumours. In very small tumours (less than or equal to 5 mm) SPF was higher as was the fraction of receptor negative tumours. Among these small cancers a hypothetical high-risk group with SPF greater than or equal to 10% and receptor-negativity will contain 7% of the patients. If SPF and receptor content are chosen as prognostic factors, the latter patients may be a group suitable for adjuvant therapy in treatment schedules. PMID- 1607035 TI - Dermatofibrosarcoma protuberans: treatment and prognosis. AB - Dermatofibrosarcoma protuberans (DFSP) is a rare tumor of the skin with a strong tendency to recur locally. Nineteen cases of DFSP are presented. In eight of them a total of 20 local recurrences occurred, in five after irradical and in three after 'narrow' excisions. After wide excision (greater than 2 cm) for primary or wide re-excision for recurrent tumor, all patients remained free of tumor with a mean follow-up of 13.2 years (range 2-28 years). An extensive literature review revealed 913 cases of DFSP. The overall recurrence rate is about 50%; after adequate wide excision, 13%. Recurrent tumor is safely treated by wide re excision and the recurrence rate is then 12%. Regional and distant recurrences are infrequent. Eleven cases (1%) were reported to have regional lymph node metastases and 37 (4%, 17 of whom were histologically confirmed) distant metastases, principally in the lung. The prognosis after appearance of regional or distant recurrence is bad. The role of radiotherapy in the management of this tumor is unclear. Primary or recurrent DFSP is best treated by surgical excision with a minimal margin of 2- preferably 3-cm of surrounding skin including the underlying fascia. Elective lymph node dissection is not advised. PMID- 1607036 TI - How common are benign subungual naevi? AB - The differentiation of subungual haematoma from benign and malignant nevoid lesions is a common clinical problem. To determine the incidence of benign subungual naevi in the general population, the digits of the hands and feet of 1000 white patients were examined. These were consecutive patients presenting to hospital for problems unrelated to the finger or toe-nail. Eight patients were found to have pigmented subungual lesions. All proved to be haematoma, although there was no history of injury. Benign subungual naevi are rare in caucasians, so subungual nevoid lesions should be regarded as malignant until proved otherwise. PMID- 1607037 TI - Dietary alcohol intake does not increase the incidence of experimentally induced mammary carcinoma. AB - There is considerable evidence from epidemiological studies that even moderate dietary alcohol intake increases the risk of breast cancer in women. The aim of this study was to test the hypothesis that dietary alcohol intake increases the incidence of mammary carcinoma in a rodent model. Two matched groups of female Sprague-Dawley rats were given 7,12-dimethylbenz[a]anthracene 15 mg by gavage when 50 days old. One group of 20 animals was given dietary ethanol at a dose of 4.4 g/kg/day in their drinking water. The incidence of tumors was significantly less in the group given ethanol (P less than 0.001). In those developing tumors, there was no significant difference between the two groups in the mean number of tumors per animal, the tumor growth rate or the time to the appearance of the first tumor. This study fails to support the hypothesis established by previous epidemiological studies. PMID- 1607038 TI - In vitro sensitized autologous tumorocidal lymphocytes to colonic adenocarcinoma. AB - We report a method of developing a population of tumorocidal lymphocytes by culturing peripheral blood mononuclear cells (PBMC) with live isogenic colorectal tumour cells in a mixed cell culture. When the proportion of PBMC to tumour cells is 100:1, eradication of the tumour cell population results. The proportion of activated lymphocytes in culture increases with cytotoxic activity as demonstrated by the presence of the cytotoxic enzyme serine esterase in the lymphocyte granules. PMID- 1607039 TI - Prognostic value of mitotic activity, eosinophilic and inflammatory reaction in stage I cancer of the uterine cervix. AB - This study includes 110 patients treated surgically for stage I squamous cell carcinoma of the cervix. The prognostic significances of mitotic activity, stromal inflammatory and eosinophilic reactions were studied. The 5-year survival rate varied from 75.0% to 93.3% and pelvic lymph node metastases (PLNM) varied from 23.0% to 31.2% according to degree of these variables. None of these pathological parameters was found to be a significant predictor of pelvic lymph node metastases and 5-year survival. PMID- 1607040 TI - A simple procedure for intrahepatic biliary drainage in patients with obstructive jaundice owing to a recurrence of cancer following reconstructive gastric surgery. AB - We designed a simple and reliable method of intrahepatic biliary drainage for patients with obstructive jaundice owing to a recurrent gastric cancer. This approach can be used for selected patients treated by partial gastrectomy and reconstructive surgery, using the Billroth II procedure and antecolic anastomosis. Anastomosis between the intrahepatic bile duct and the afferent jejunal loop is performed at the anterior edge of the liver, thus facilitating the prevention of recurrence of jaundice caused by tumor infiltration. Application of this technique led to a long-term palliation, control of the jaundice and a fairly normal life. PMID- 1607041 TI - The right approach to carcinoma of the cardia: preliminary results. AB - Surgical treatment of carcinoma of the lower oesophagus and cardia can be compromised by technical difficulties associated with inadequate exposure of the operative field. This may lead to anastomotic failure or local recurrence. A simultaneous right abdominothoracic approach to the oesophagogastric junction without division of either the costal margin or diaphragm facilitates access, allowing radical resection and the performance of a safe anastomosis without the necessity of redraping the patient part way through the procedure. Maintaining the costal margin and diaphragm reduces the pulmonary problems associated with a conventional abdominothoracic incision. Thirty two consecutive patients who have been operated upon between 1983 and 1990 using the synchronous right abdominothoracic approach and who have had a stapled anastomosis have been reviewed. The post-operative complication rate was low and the 5 year survival figure is 17%. PMID- 1607042 TI - Prediction of survival time after curative surgery for advanced gastric cancer. AB - This study was carried out to define independent prognostic factors influencing survival time and to examine the survival time of patients with advanced gastric cancer treated by curative resection. Six hundred and forty-eight patients were identified of whom 275 patients died of tumor recurrence during follow-up. Univariate analysis using Mantel-Cox analysis, indicated that tumor size, tumor location, gross appearance, degree of gastric wall invasion, lymph node metastasis and operative procedures were significant factors related to survival time (P less than 0.01 to P less than 0.05). Multivariate analysis using the Cox proportional hazard model adjusted for sex, age and other factors, suggested that tumor size (P less than 0.01, relative risk = 1.79), degree of gastric wall invasion (P less than 0.01, rr = 1.24) and lymph node metastasis (P less than 0.01, rr = 2.39) were the most independent prognostic factors statistically, although these three prognostic factors were inter-related. When the tumor is less than 5 cm and there is no serosal invasion or lymph node metastasis, then a longer survival time can be expected (88.7% at 5-years). If the tumor size exceeds 10 cm and there is invasion into neighboring structures and lymph node metastases, then survival time will be short (11.9% at 4-years). PMID- 1607043 TI - Xanthogranuloma of the stomach: a case report. AB - A case of xanthogranuloma of the stomach causing clinical signs and symptoms suggestive of gastric cancer is reported. The pathological findings and the malignant potential of this lesion are discussed. PMID- 1607044 TI - Duodenal carcinoid tumour associated with gastric leiomyoblastoma. AB - We describe the synchronous occurrence of carcinoid tumour of the duodenum and leiomyoblastoma of the stomach in a patient presenting with anaemia. This combination of primary tumours has not previously been described. PMID- 1607045 TI - Stemming the tide? Assessing the deterrent effects of the Immigration Reform and Control Act. AB - This study uses a new source of data to assess the degree to which the Immigration Reform and Control Act (IRCA) deterred undocumented migration from Mexico to the United States. Data were collected from migrants interviewed in seven Mexican communities during the winters of 1987 through 1989, as well as from out-migrants from those communities who subsequently located in the United States. We conduct time-series experiments that examine changes in migrants' behavior before and after passage of the IRCA in 1986. We estimate trends in the probability of taking a first illegal trip, the probability of repeat migration, the probability of apprehension by the Border Patrol, the probability of using a border smuggler, and the costs of illegal border crossing. In none of these analyses could we detect any evidence that IRCA has significantly deterred undocumented migration from Mexico. PMID- 1607046 TI - Playing cat and mouse at the U.S.-Mexican border. AB - Border control and apprehension activity represents a major element of the Immigration Reform and Control Act of 1986. Does apprehending an undocumented migrant deter remigration? If it does not, does it change future migration behavior? I explore these questions by testing hypotheses about the effects of apprehension on the actual and desired length of stay in the United States and on the frequency of migration for undocumented Mexican male migrants. Results suggest that INS policy may well be backfiring. Migrants stay in the United States longer on non-apprehended trips and stay in Mexico for shorter spells between trips to compensate for the cost of a past apprehension. PMID- 1607047 TI - Immigrants, visible minorities, and self-employment. AB - Historically, self-employment was perceived as a mechanism whereby immigrants could circumvent discriminatory practices in wage labor. More recent research by Borjas in the United States, however, suggests that this view is incorrect. Immigrants, particularly members of visible minorities, are disadvantaged in both the wage labor and the self-employed markets. This pattern has not been replicated in Canada, however; after controlling for several socioeconomic attributes, it is found that foreign-born, self-employed visible minority-group members are not at a disadvantage in relation to the majority population. Foreign born visible minority group members earn less, however, in the wage labor force. In contrast, it was found that there is no statistically significant difference between native-born visible minority group members and others in the wage labor force, and that native-born, self-employed minority-group members may earn more than others in that market segment. PMID- 1607048 TI - Religion and fertility in the United States: new patterns. AB - In the United States, the baby boom-era pattern of high Catholic and low Protestant fertility has ended. Among non-Hispanic whites in the 1980s, Catholic total fertility rates (TFRs) were about one-quarter of a child lower than Protestant rates (1.64 vs. 1.91). Most of the Protestant-Catholic difference is related to later and less frequent marriage among Catholics. Future research on the demography of religious groups should focus on explaining the delayed marriage pattern of Catholics, the high fertility of Mormons and frequently attending Protestants, and the very low fertility of those with no religious affiliation. PMID- 1607049 TI - Taxes and the family: the impact of the tax exemption for dependents on marital fertility. AB - In this paper I use data from the Panel Study on Income Dynamics to examine the relationship between the dependent exemption feature of the United States federal income tax (an unambiguous subsidy to dependents) and the fertility behavior of married couples over the period 1979-1983. The exemption decreases the price of a child to a household, thus having a direct relationship to the timing and/or number of children observed in a family. Conditional logit results support this hypothesis by showing that the exemption has a positive and significant impact on the likelihood of having a birth during the period under study. PMID- 1607050 TI - Age at last birth and its components. AB - This paper examines the ways in which the behavior of twentieth century cohorts of American women changed simultaneously in the three components of fertility that determine age at last birth--age at first birth, spacing between subsequent births, and parity progression ratios of subsequent births--to produce changes in the timing of the completion of childbearing. It decomposes changes in the mean age at last birth among cohorts and between whites and nonwhites to changes in these three components. To perform these analyses, we developed and applied a method to estimate the distributions and means of ages and last births, birth intervals, and parity progression ratios from age- and parity-specific fertility rates available from vital statistics data. Results show that the cohorts increased and decreased their age at first birth, birth intervals, and parity progression ratios of lower and higher birth orders in almost every possible combination so as to achieve a relatively young age at final birth. PMID- 1607051 TI - Marriage markets and nonmarital fertility in the United States. AB - We merge census microdata with vital statistics data to examine the effect of women's marriage opportunities on nonmarital fertility rates and ratios across 75 U.S. metropolitan areas. Measures of the quantity and "quality" of marriageable men simultaneously specific for women's age, race, education, and place of residence reveal especially poor marriage prospects for highly educated black women. The effect of mate availability on nonmarital fertility is generally modest. Among white women, marriage opportunities are associated inversely with the nonmarital fertility rate, perhaps reflecting an increased likelihood that a premarital conception will be legitimated. Marriage opportunities also reduce nonmarital fertility ratios for young black and white women. The nonmarital fertility rate is lower among women whose marriage pool includes a large percentage of nonemployed males. Only a small proportion of the racial difference in nonmarital fertility appears attributable to differences in the marriage markets of black and of white women. PMID- 1607052 TI - Personality traits and developmental experiences as antecedents of childbearing motivation. AB - Childbearing motivation may be conceptualized as based upon psychological traits and shaped by experiences during childhood, adolescence, and early adult life. This paper explores what those traits and developmental experiences are. Two measures of childbearing motivation, one positive and the other negative, are described. Using a sample of 362 married men and 354 married women, the paper systematically examines the factors associated with these measures. In addition to a set of basic personality traits, these factors include parental characteristics, teenage experiences, and a number of variables from young adult behavior domains such as marriage, education, work, religion, and parental relationships. Stepwise multiple regression analyses lead to two final constrained, simultaneous-equation regression models. These models indicate the importance of both personality traits and diverse life-cycle experiences in the development of childbearing motivation, the differential gender distribution of predictors, and the different experiential antecedents of positive and negative motivation. PMID- 1607053 TI - Living and dying in the U.S.A.: sociodemographic determinants of death among blacks and whites. AB - This paper examines the demographic and social factors associated with differences in length of life by race. The results demonstrate that sociodemographic factors--age, sex, marital status, family size, and income- profoundly affect black and white mortality. Indeed, the racial gap in overall mortality could close completely with increased standards of living and improved lifestyles. Moreover, examining cause-specific mortality while adjusting for social factors shows that compared to whites, blacks have a lower mortality risk from respiratory diseases, accidents, and suicide; the same risk from circulatory diseases and cancer; and higher risks from infectious diseases, homicide, and diabetes. These results underscore the importance of examining social characteristics to understand more clearly the race differences in overall and cause-specific mortality. PMID- 1607054 TI - Birth spacing and child mortality in Bangladesh and the Philippines. AB - This analysis uses data from Bangladesh and the Philippines to demonstrate that children who are born within 15 months of a preceding birth are 60 to 80% more likely than other children to die in the first two years of life, once the confounding effects of prematurity are removed. The risks associated with short conception intervals are confined to children who are also high birth order; they persist in the presence of controls for prior familial child mortality, breast feeding, mother's age, and socioeconomic status. In Bangladesh but not in the Philippines, these effects are confined to the neonatal period. PMID- 1607055 TI - Perinatal AIDS. AB - AIDS is the major public health concern today. The short-term history of the disease adds considerable emphasis to the problem in that it has literally exploded in a few years. The pathophysiology and natural history and, what is most important, the treatment, remain enigmatic. Management of women at risk of HIV infection is colored by the nature of the illness, the subgroups of the people first infected, the mode of transmission, and the implication of vertical transmission. PMID- 1607056 TI - Long-term effects of time, medical treatment and pregnancy in 176 hyperprolactinemic women. AB - The changes in plasma prolactin (PRL) concentrations were studied in 176 hyperprolactinemic women over periods of 6-180 months, to evaluate the independent effects of time, drugs and pregnancy on the evolution of prolactinemia. CT scans showed pituitary adenoma in 87 (9 macroadenoma), the clinical presentations for 110 patients there amenorrhea, for 37 abnormal cycles and 29 had anovulatory sterility as an isolated symptom. 107 women underwent 191 cycles of dopaminergic treatment and 73 had pregnancies (86), either spontaneously or as a consequence of the treatment. Changes in prolactin induced by medical treatment and pregnancy were recorded and the spontaneous changes in prolactin in 38 patients (17 with adenoma) were followed over periods of 6-72 months. Final mean PRL concentrations were lower than basal though not significantly, in both 'functional' (54.4 vs. 79.2 ng/ml) and prolactinoma patients (87.3 vs. 116.4 ng/ml). Separate calculation of changes in prolactin after the course of medical treatment, pregnancies or 'just waiting' periods showed mean PRL concentrations to be significantly lower only for 'functional' patients after pregnancy. On the other hand, PRL variations in individual patients revealed that: (1) spontaneously, PRL rarely becomes lower over a few years; (2) dopaminergic treatment was associated with normalization of PRL in 13% of women; and (3) pregnancy normalized prolactin concentrations in 29% of the patients. Chi-square analysis of the PRL-lowering frequencies in functional patients showed a high cure rate for pregnancy (P less than 0.0001) and a lesser but still significant effect of drugs (P less than 0.025). PMID- 1607057 TI - Multifetal pregnancy reduction: comparison of obstetrical results with spontaneous twin gestations. AB - Thirty-two multifetal pregnancies were reduced to twin gestations. Our control group was composed of 32 spontaneous twin gestations. The comparison of these two groups did not show that the procedure altered obstetrical results as far as duration of gestation, birth weight and rate of dismaturity are concerned. PMID- 1607058 TI - Characteristics of bacteriuria in a homogeneous maternity hospital population. AB - Bacteriuria and urinary tract infection are a common cause of morbidity in pregnancy. Recent evidence has, however, questioned the magnitude of this risk and the effectiveness of therapy in reducing it. To clarify matters, a prospective study on 3123 ante-natal women was carried out. Screening for bacteriuria was carried out by culturing a mid-stream specimen of urine. Treatment was given to all patients with a positive culture and was based on antibiotic sensitivity testing. Repeat culture was performed 1 week after completion of therapy. The prevalence of bacteriuria in our population was 4.74%. Over half of these patients were asymptomatic. 67% of those with bacteriuria at screening were symptomatic or had a past history of urinary tract infection. Escherichia coli was the predominant organism cultured. The most effective antibiotic was Nitrofurantoin, which was sensitive in over 90% of isolates. Late urinary tract infection occurred in 3.52% of patients. There was no increase in maternal or foetal complications amongst those with bacteriuria. We concluded that it might be more cost-effective to confine screening to those patients who are symptomatic or have a past history of urinary tract infection. PMID- 1607060 TI - Usefulness of urodynamic investigations in female incontinence. AB - Urinary incontinence in females has been evaluated in a prospective series of 408 patients by comparing the clinical diagnosis and the subsequent urodynamic findings. The presenting symptoms or combination of symptoms were shown to have only a limited diagnostic predictive value as measured by urodynamic diagnostic criteria. The symptom of stress incontinence was a sensitive detector of genuine stress incontinence (94% sensitivity) but was not very specific (65%). The symptoms of urgency and urge incontinence were found to have limited sensitivity (62%) and specificity (47%) in the detection of detrusor instability. Even patients with isolated complaints of stress incontinence have an incidence of detrusor instability of 52%, whereas 76% of those with a history of isolated urgency and urge incontinence had detrusor instability. An urodynamic evaluation should be performed on most female patients suffering from urinary incontinence and is essential for patients who are being considered for surgery of stress incontinence. PMID- 1607059 TI - Relationship of age at menarche and subsequent fertility. AB - We investigated retrospectively the relationship between the age at menarche and reproductive ability in 2278 married women. Those who had a pregnancy experienced menarche at a mean age (+/- SEM) of 13.7 +/- 0.1 years, and those who were infertile had menarche at a mean age of 14.0 +/- 0.2 years, difference in the times of onset of menarche being significant (P less than 0.05). Moreover, a group in whom menstruation started after the age of 18 years had a significantly higher rate of infertility (15.7%) than the others (5.0%). Irregular menstruations during the first few years after menarche was also related to decreased reproductive ability. These findings indicate the importance of menarche before the age of 18 for normal reproductive functioning. PMID- 1607061 TI - Expression of CEA, CA-125 and SCC antigen by biological fluids associated with pregnancy. AB - Carcinoembryonic antigen (CEA), cancer antigen 125 (CA-125) and squamous cell carcinoma (SCC) antigen were measured in 56 full-termed pregnancies by enzyme immunoassays (EIA-MEIA). The measurements were done in maternal serum (MS), umbilical cord blood (UCB) and amniotic fluid (AF) samples, during delivery. Very high antigen levels were found in AF samples (median: CEA = 124 ng/ml; CA-125 = 710 U/ml; SCC = 710 ng/ml) compared to UCB and MS. CEA and SCC showed significantly lower values in MS (0.6 and 1.7 ng/ml, respectively) than in UCB (1.6 ng/ml, P = 7.7 x 10(-9); 3.55 ng/ml, P = 6.5 x 10(-6), respectively), while CA-125 had significantly higher values in MS (6 U/ml) than in UCB (0.0 U/ml, P = 17 x 10(-6); Wilcoxon paired test). All CEA values in MS were below cut-off (less than or equal to 5 ng/ml), while 10% of CA-125 and 30% of SCC values were above cut-off (less than or equal to 35 U/ml and less than or equal to 2.5 ng/ml, respectively). Amniotic fluid CEA with meconium had higher values (P = 0.0002), while the highest CA-125 values in AF samples were found in primiparae (P = 0.02). Moreover SCC in AF samples from vaginal delivered pregnancies showed significantly higher values, compared to those from cesarean section (P = 4.2 x 10(-7); Mann-Whitney U-test). Thus, our findings suggest that pregnancy has an influence on maternal serum SCC and CA-125 values, while CEA is independent of gestation and seems to conserve its diagnostic value during pregnancy as well. PMID- 1607062 TI - The mucosa of the rabbit vagina: a proposed experimental model for correlated morphofunctional studies in humans. AB - In order to suggest a valid experimental model for correlated studies regarding the complex phenomena of reproductive biology in humans, light (LM), transmission (TEM) and scanning electron microscopic (SEM) observations were carried out on vaginae of sexually mature New-Zealand albino rabbits, both in estrus and at 5 h after mating. To avoid artifacts depending upon the operative times for specimen removal and, in particular, to well visualize the inner surface of this organ, vaginal irrigation with fixative was performed prior to the surgical removal. Our data demonstrate that the upper 2/3 of the vaginal duct form a kind of 'cervico vaginal canal' which shares many histological features with the human endocervix. In fact, this portion is lined within by a monostratified epithelium provided with tall microvillous and ciliated cells and often invaginated in crypts. After mating, the microvillous cells showed evidence of secretory activity, exhibiting dome-like luminal surfaces. Secretory droplets often contacted cilia and spermatozoa present in the mucosal furrows and crypts. Because of these singular features and the morphofunctional interactions between vaginal epithelium and male gametes, we believe the rabbit to be a helpful model for comparative biology in humans, concerning sperm capacitation and the general reactivity of the female genital tract during the reproductive cycle. PMID- 1607063 TI - Premature labour induced by cortisol in the unrestrained pregnant rabbit. AB - The relationship between electrical activity (EMG) of the uterus, progesterone levels and gap junctions was studied in pregnant rabbits delivering either prematurely (cortisol-induced) or spontaneously at term. Electrodes were implanted in the myometrium and a catheter was inserted into the jugular vein for continuous infusion of saline or cortisol from gestational age 25 days. A tether and swivel system was used to connect the electrodes and catheter to the recording unit thus allowing protection of the wires and catheters while enabling the rabbit to move freely. The EMG was recorded continuously from day 25 of pregnancy until animals either delivered or were sacrificed at predetermined days of gestation. Both rabbit groups showed a similarity in patterns of EMG, progesterone levels and gap junction formation. We conclude that preterm labour induced by cortisol mimics normal term labour. PMID- 1607064 TI - Uterine rupture following conservative surgery for interstitial pregnancy. AB - A case of uterine rupture following conservative surgery for interstitial pregnancy is presented. Even though the uterine cavity was not opened during removal of the ectopic pregnancy, attenuation of the muscle lead to subsequent rupture of the uterus in the second trimester. The option for medical termination of ectopic pregnancies located in the cornual portion of tubes is discussed. PMID- 1607065 TI - Successful pregnancy in a patient with a single ventricle. AB - Single ventricle is an uncommon form of congenital heart disease. We report a successful pregnancy and delivery in a mother with surgically confirmed single ventricle. PMID- 1607066 TI - Mapping diabetes-susceptibility genes. Lessons learned from search for DNA marker for maturity-onset diabetes of the young. AB - During our search for a marker for non-insulin-dependent diabetes mellitus (NIDDM) in a large multigenerational family with a form of NIDDM termed maturity onset diabetes of the young (MODY), we learned a great deal that may serve to streamline the search for diabetes-susceptibility genes in other families. We describe here our experience and suggest strategies that may enhance the search for markers for other diabetes susceptibility genes with genetic linkage approaches. PMID- 1607067 TI - Detection of mutations in insulin receptor gene by denaturing gradient gel electrophoresis. AB - Denaturing gradient gel electrophoresis (DGGE) has been used to screen for mutations in the insulin receptor gene. Each of the 22 exons was amplified by the polymerase chain reaction (PCR). For each exon, one of the two PCR primers contained a guanine-cytosine (GC) clamp at its 5' end. The DNA was analyzed by electrophoresis through a polyacrylamide gel containing a gradient of denaturants. Two geometries for the gels were compared; the gradient of denaturants was oriented either parallel or perpendicular to the electric field. The sensitivity of the technique was evaluated by determining whether DGGE succeeded in detecting known mutations and polymorphisms in the insulin receptor gene. With parallel gels, 12 of 16 sequence variants were detected. The use of perpendicular gels increased the sensitivity of detection so that all 16 sequence variants were successfully detected when DNA was analyzed by a combination of perpendicular and parallel gels. Furthermore, DGGE was used to investigate a patient with leprechaunism whose insulin receptor genes had not previously been studied. Two mutant alleles were identified in this patient. The allele inherited from the father had a mutation substituting alanine for Val-28; in the allele inherited from the mother, arginine was substituted for Gly-366. PMID- 1607068 TI - Major gene effect for insulin levels in familial NIDDM pedigrees. AB - Insulin resistance and hyperinsulinemia are familial traits that may precede and predict the onset of non-insulin-dependent diabetes mellitus (NIDDM). In some populations, the distribution of fasting insulin levels and measures of in vivo insulin action suggest the effects of a single major gene. We previously noted hyperinsulinemia among unaffected members of 16 large white pedigrees ascertained through two or more NIDDM siblings. To examine the hypothesis that insulin levels are determined by a single major genetic locus, we used segregation analysis to examine fasting insulin levels in 206 family members and 65 spouses who had normal glucose tolerance tests by World Health Organization criteria. Segregation analysis supported a major locus determining fasting insulin levels and segregating as an autosomal recessive allele with a frequency of 0.25. Thus, homozygotes represented 6.25% of the population, and homozygosity for the hyperinsulinemia allele elevated the mean fasting insulin level from 70.3 to 211.1 pM (11.7-35.2 microU/ml). The analysis apportioned the variance in fasting insulin as 33.1% due to the major autosomal locus, 11.4% due to polygenic inheritance, and 55.5% due to unmeasured effects. Homozygotes for the recessive allele had higher 1-h insulin levels than all others (911.7 vs. 427.2 pM [152.0 vs. 71.2 microU/ml]). We also found evidence for a major locus determining 1-h stimulated insulin levels, with codominant inheritance as the most likely pattern in inheritance. The causal relationship between these findings and NIDDM has not been determined, and segregation of direct measures of insulin action remains to be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607069 TI - Growth hormone stimulates skeletal muscle protein synthesis and antagonizes insulin's antiproteolytic action in humans. AB - We examined the effects of a combined, local intra-arterial infusion of growth hormone (GH) and insulin on forearm glucose and protein metabolism in seven normal adults. GH was infused into the brachial artery for 6 h with a dose that, in a previous study, stimulated muscle protein synthesis (phenylalanine Rd) without affecting systemic GH, insulin, or insulinlike growth factor I concentrations. For the last 3 h of the GH infusion, insulin was coinfused with a dose that, in the absence of infused GH, suppressed forearm muscle proteolysis by 30-40% without affecting systemic insulin levels. Measurements of forearm glucose, amino acid balance, and [3H]phenylalanine and [14C]leucine kinetics were made at 3 and 6 h of the infusion. Glucose uptake by forearm tissues in response to GH and insulin did not change significantly between 3 and 6 h. By 6 h, the combined infusion of GH and insulin promoted a significantly more positive net balance of phenylalanine, leucine, isoleucine, and valine (all P less than 0.05). The change in net phenylalanine balance was due to a significant increase in phenylalanine Rd (51%, P less than 0.05) with no observable change in phenylalanine Ra. For leucine, a stimulation of leucine Rd (50%, P less than 0.05) also accounted for the change in leucine net balance, with no suppression of leucine Ra. The stimulation of Rd, in the absence of an observed effect on Ra, suggests that GH blunts the action of insulin to suppress proteolysis in addition to blunting insulin's action on Rd. PMID- 1607070 TI - Risk of early-onset proliferative retinopathy in IDDM is closely related to cardiovascular autonomic neuropathy. AB - Determinants of proliferative diabetic retinopathy (PDR) that occur during the 2nd decade of insulin-dependent diabetes mellitus (IDDM) (early-onset PDR) were investigated in a nested case-control study. From an inception cohort of patients with juvenile-onset IDDM that now has 15-21 yr diabetes duration, the patients with PDR (cases, n = 74) were selected for study along with a random sample of the patients in the cohort without PDR (control subjects, n = 88). The risk of PDR was associated with poor glycemic control during the first 12 yr of diabetes. Relative to patients in the first quartile of the index of hyperglycemia, those in higher quartiles and nonattenders had a four- to fivefold risk of developing PDR. A striking relationship with cardiovascular autonomic neuropathy (CAN) was found. Relative to patients without CAN, patients with significant and mild CAN had odds ratios of 77.5 and 34.6, respectively. Patients with albumin excretion rates greater than 30 micrograms/min had moderately increased risk of PDR (ranging from 4-fold for microalbuminuria to 7-fold for proteinuria). In contrast, patients with impaired renal function had an extremely high risk of PDR. All 20 of these patients were cases, therefore the odds ratio was infinite. All three factors (poor glycemic control, CAN, and various stages of nephropathy) were associated with PDR in multiple logistic regression analysis. However, in models including glycemic control, the association between microalbuminuria or proteinuria and PDR was weakened. In conclusion, our findings are consistent with a hypothesis that the level of glycemia is a primary determinant of early-onset PDR.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607071 TI - Glycerol production and utilization during the early phase of human obesity. AB - To study the initial period of fat deposition in human obesity, we measured glycerol turnover in 12 children of 135-253% ideal body weight, who had continuously gained weight since the onset of obesity 2-9 yr previously. Hyperinsulinemia developed in these children depending on obesity duration (r = 0.74, P less than 0.01). Whole-body glycerol production was twofold greater in the obese children (311 vs. 156 mumol.min-1, P less than 0.01) and correlated with body fat (r = 0.67, P less than 0.005). Normalization of glycerol flux to fat mass revealed that the rate of triglyceride hydrolysis was in fact lower in the adipose tissue of obese children (9.4 vs. 17.7 mumol.min-1/kg body fat) and correlated with plasma insulin (r = 0.64, P less than 0.005). Euglycemic insulin clamps showed that the response of glycerol production to a unit increment in plasma insulin concentration was increased in obese children, suggesting increased insulin sensitivity of adipose tissue. As a direct consequence (r = 0.67, P less than 0.025) of their elevated plasma glycerol concentration (65 +/- 4 vs. 37 +/- 2 microM, P less than 0.05) obese children had an increased glycerol utilization by the whole body, as well as per unit of lean body mass (9.1 +/- 1 vs. 6.5 +/- 0.9 mumoles.min-1.kg lean body mass-1, P less than 0.025). PMID- 1607072 TI - Encapsulation of insulin for oral administration preserves interaction of the hormone with its receptor in vitro. AB - It has been shown that insulin associated with nanocapsules of isobutylcyanoacrylate retains biological activity after oral administration to diabetic rats from 6 to 21 days. Because part of this action is unexplained, we focused on the interaction of encapsulated insulin with the insulin receptor in vitro. We have shown that encapsulated insulin is able 1) to bind to insulin receptors both in rat liver plasma membranes and after solubilization from Chinese hamster ovary (CHO) cells transfected with the gene of human insulin receptor, 2) to accelerate 125I-labeled insulin dissociation from its receptor, and 3) to ensure transduction of a signal leading to stimulation of the beta subunit phosphorylation, with parameters similar to those of native insulin. In addition, encapsulated 125I-insulin was rapidly internalized in transfected CHO cells. Analysis of cell-associated radioactivity showed that encapsulated insulin remained largely intact (greater than 80%) after 3 h, whereas native insulin was mostly degraded. These data indicate that encapsulated insulin fulfills all the earliest events at the receptor level leading to biological actions and suggests that encapsulation protects insulin against insulin degradation inside the cells. PMID- 1607073 TI - Genetic and environmental determinants of type II diabetes in Mexico City and San Antonio. AB - To study genetic and environmental determinants of non-insulin-dependent (type II) diabetes, we compared a random sample of 35- to 64-yr-old Mexican-American men and women living in several low-income barrio neighborhoods of San Antonio to similarly aged Mexicans living in a low-income colonia of Mexico City (Colonia Liberales). A total of 1138 Mexican Americans, representing 64.3% of the original sample, and 646 Mexicans, representing 69.2% of the original sample, participated in the survey. Diabetes was diagnosed using World Health Organization criteria. Genetic susceptibility to type II diabetes was inferred from the percentage of Native American genetic admixture as estimated from skin reflectance measurements. The prevalence of diabetes was 36% higher among San Antonio Mexican Americans than among Mexicans in Mexico City; this difference was highly statistically significant (age- and sex-adjusted prevalence ratio 1.36, P = 0.006). This excess was observed despite the fact that genetic susceptibility, as inferred from the admixture estimates, was similar in the two cities. On the other hand, Mexicans were somewhat leaner as measured by body mass index and skin folds. Mexican women consumed fewer total calories than Mexican-American women, but there was no difference in the caloric intake of men. Mexico City residents ate less fat (18-19% of total calories vs. 31-32% in San Antonio, P less than 0.001), more carbohydrate (64-65 vs. 49%, P less than 0.001), and performed more physical activity than San Antonio Mexican Americans. Mexicans appeared to consume more refined sugar than Mexican Americans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607074 TI - Beneficial effect of intravenous bolus of corticotropin-releasing factor on glucose intolerance of genetically obese (fa/fa) rats. AB - The effect of an ovine corticotropin-releasing factor (oCRF) bolus administered intravenously at the onset of glucose ingestion during oral glucose tolerance tests (OGTTs) was evaluated in conscious lean (FA/FA) and genetically obese (fa/fa) rats. When the amount of oCRF was purposely small to not stimulate the hypothalamo-pituitary-adrenal (HPA) axis, it normalized the glucose intolerance of genetically obese rats as tested during OGTTs and decreased their insulin output, whereas it had no effect in lean rats. In obese rats, plasma xylose levels measured after the ingestion of a xylose load were unaltered by the intravenous oCRF bolus, indicating that the beneficial effect of oCRF on glucose intolerance of fa/fa rats was unlikely to be dependent on glucose absorption. When the intravenous bolus of oCRF was doubled at the onset of OGTTs, it stimulated the HPA axis and produced a worsening of glucose intolerance in obese rats together with an increase in their insulin response. Again, it had no effect in lean rats. The abnormal intravenous glucose tolerance of obese rats was unaffected by the administration of an oCRF bolus: This is in keeping with previous data showing that bypassing the oral cavity fails to elicit several sensory reflexes that markedly influence subsequent glucose clearance. It has been suggested that obese rats may have deficient oropharyngeal reflexes that could be reactivated by the oCRF bolus, thereby being responsible for the normalization of their impaired OGTT, which lies in the hepatic glucose production process. PMID- 1607075 TI - Coordinate regulation of amylin and insulin expression in response to hypoglycemia and fasting. AB - Amylin is a 37-amino acid peptide synthesized in the pancreatic beta-cell and cosecreted with insulin. In situ hybridization of nondiabetic rat pancreas shows that insulin and amylin RNA are both localized within the islet of Langerhans in a similar distribution. After 12 days of insulin-induced hypoglycemia (mean blood glucose 3.0 +/- 0.4 mM [54 +/- 8 mg/dl]), both insulin and amylin RNA fell greater than 95%. However, maintenance of euglycemia by simultaneous infusion of glucose with insulin did not suppress insulin or amylin RNA. Fasting suppressed amylin and insulin secretion from the isolated, perfused pancreas 70 and 58%, respectively, and with refeeding, secretion rates recovered to fed levels. Despite these changes in the rates of secretion, the relative ratio of amylin to insulin was not significantly different in fed, fasted, or refed rats. The molar ratio of insulin to amylin was estimated to be 100:2.3-2.6. Both insulin and amylin RNA was suppressed approximately 50% in response to fasting. Thus, although the absolute amounts of insulin and amylin change substantially under the conditions tested, the relative amounts of these peptides do not change. PMID- 1607076 TI - NIDDM associated with mutation in tyrosine kinase domain of insulin receptor gene. AB - A population of 103 patients with non-insulin-dependent diabetes mellitus (NIDDM) was screened for mutations in the tyrosine kinase domain of the insulin receptor gene. Patient genomic DNAs corresponding to exons 17-21 of the insulin receptor gene have been amplified by polymerase chain reaction and analyzed by denaturing gradient gel electrophoresis (DGGE). One patient was identified with an altered pattern of mobility of exon 20 in the DGGE assay. Direct sequence of amplified DNA showed a single nucleotide substitution in the codon 1152 (CGG-- greater than CAG), resulting in the replacement of Arg with Gln. Two bands appeared in the sequence of exon 20 of the insulin receptor (nucleotide position 3584), indicating that this patient was heterozygous for the mutation. Insulin binding to intact erythrocytes from the patient was in the normal range. Although autophosphorylation of the purified insulin receptor also seemed normal, its kinase activity toward the exogenous substrate poly Glu:Tyr (4:1) was undetectable. This mutation may impair insulin receptor kinase and contribute to insulin resistance in this patient. PMID- 1607077 TI - Staphylococcal enterotoxin-activated spleen cells passively transfer diabetes in BB/Wor rat. AB - BB/Wor rats develop spontaneous autoimmune diabetes similar to human insulin dependent diabetes mellitus. A T-cell-mediated pathogenesis for BB/Wor diabetes is indicated because disease is prevented by neonatal or adult thymectomy and treatment of diabetes-prone rats with monoclonal antibodies directed against CD5 or CD8 T-cell surface markers. Disease can be adoptively transferred with injections of concanavalin A-activated spleen cells from either acutely diabetic or RT6.1 T-cell-depleted diabetes-resistant BB/Wor rats. We used microbial superantigens to stimulate spleen cells from RT6.1 T-cell-depleted diabetes resistant rats and demonstrated that such cells activated with staphylococcal enterotoxins (SEs) can also transfer diabetes. The diabetogenic effector T cells are readily activated by SEA, SEC3, and SEE, whereas SEB- and SEC2-activated cells are far less effective in the adoptive transfer of diabetes. These results demonstrate that microbial superantigens are capable of activating self-reactive and diabetes-inducing T cells in vitro in the BB/Wor rat. Ubiquitous microorganisms may be the environmental trigger for autoimmunity in susceptible individuals. PMID- 1607078 TI - Mechanisms involved in degradation of human insulin by cytosolic fractions of human, monkey, and rat liver. AB - The degradation of native and 125I-labeled human insulin (HI) was examined in the cytosolic fraction of human, monkey, and rat liver. The purpose of these studies was to provide a species comparison of the interaction of insulin-degrading enzyme (IDE) and protein disulfide isomerase (PDI) in the degradation of HI. Western-blot analysis with monoclonal antibodies indicated the presence of both IDE and PDI in the cytosolic fraction of human and monkey liver. In contrast, rat liver cytosol contained, detectable levels of IDE only. A species comparison of metabolic profiles was performed by fractionating peptide products with reversed phase high-performance liquid chromatography. After a 60-min incubation, human liver cytosol degraded unlabeled HI into three major products. Two of these peptides coeluted with the products of the incubation of HI with purified rat liver PDI. The three peptides were isolated and determined by NH2-terminal sequence analysis to be intact A chain, B chain, and des(Phe1)-B chain. Human liver cytosol also formed 125I-A chain and 125I-B chain as major products when specifically labeled 125I-HI isomers were used as substrate. Significant proteolytic degradation was observed only when reactions with human liver cytosol were supplemented with Mn2+. In contrast, monkey and rat liver cytosol proteolytically degraded 125I-HI isomers to small peptide fragments. The rat and monkey metabolic profiles were similar to each other and to that observed with Mn(2+)-supplemented human liver cytosol. Proteolysis in monkey and rat was sensitive to inhibition by EDTA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607079 TI - Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus. AB - Insulin-dependent diabetes mellitus (IDDM) is marked by circulating antibodies to a 64,000-M(r) islet cell antigen identified as glutamic acid decarboxylase (GAD). We describe a radioimmunoprecipitation assay with GAD isolated from pig brain. The sera tested were from 80 patients with IDDM including 26 with disease of recent onset and 54 with disease of longer duration (3-42 yr), 20 with non insulin-dependent diabetes mellitus (NIDDM), and 55 nondiabetic subjects. Conventional assays for islet cell cytoplasmic antibodies were performed concurrently. The level of antibody in serum was expressed in units based on percentage reactivity of a standard reference serum. The frequency of antibody to GAD in IDDM was 69% in short-duration cases and 59% in long-duration cases. The latter was substantially higher than the frequency of islet cell cytoplasmic antibody. Antibodies to GAD were elevated (means +/- 3 SD) in 5% NIDDM cases and in none of the nondiabetic subjects. A simple laboratory test with a defined autoantigen has substantial implications for population screening and early diagnosis of IDDM and for better understanding of its pathogenesis. PMID- 1607080 TI - Endoscopic resection of large sessile colorectal polyps. AB - Colonoscopic removal of large, sessile polyps is difficult, but can be successfully carried out by experienced endoscopists. "Piecemeal" resection with an electrocautery snare was performed at our institution in 108 patients with 132 such lesions. The mean size of the unresected polyps was 3.0 cm. Complications occurred in 3.0% of polypectomies (3.8% of patients), with bleeding necessitating transfusion in 2.3% of polypectomies (2.8% of patients), and microperforation (probable) in the remainder. No patient required emergency surgery due to a complication. In 65 patients (60%), colonoscopic resection and follow-up alone was carried out. Of these, adenomas recurred/persisted in 28%, most of which were successfully re-resected. Nearly half of all recurrent polyps occurred after at least one negative intervening examination. Carcinoma later appeared in 17% of the recurrences despite apparent initial complete resection of a previously benign polyp. Cure was ultimately achieved in 88% of endoscopically managed patients. Surgical resection was required in 27% of patients, mostly following the initial polypectomy when invasive carcinoma was found in the specimen. No residual tumor was later found in 41% of the colon specimens from these patients. Ninety-one percent of cancers were favorable stage, whether discovered early or late. Follow-up colonoscopy was achieved in 77% of patients over an average of 3.7 years. Metachronous polyps were excised in 52 patients (63%) and metachronous carcinoma was diagnosed in 3 patients (3.6%). An aggressive regimen of surveillance colonoscopy is warranted in these patients to detect and manage local recurrences and to remove subsequent adenomas. Endoscopic resection of large sessile adenomas can be safe and effective. PMID- 1607081 TI - Cold snare excision of small colorectal polyps. AB - This study describes a new technique for excision of small colorectal polyps in a series of 210 consecutive patients, who had total colonoscopy, and in whom any clotting problems had been excluded. A total of 288 small polyps of 5 mm or less in diameter were transected by mechanical strangulation with a polypectomy snare, but without applying any electrical energy. All polyps were recovered whole and sent for histologic examination. No case of perforation, serious bleeding, or mortality was recorded, nor was there any need for blood transfusion because of sudden or delayed bleeding. Of the small polyps, 56% were adenomas, 43% hyperplastic, and 1% were other types. No invasive cancer was found, but in seven small adenomas severe dysplasia was observed. No correlation between the macroscopic appearance of small polyps at endoscopy and their nature at histology was found. Our data confirm that all visible polypoid lesions of the colon should be removed, and that cold snare excision of small polyps is a safe and effective alternative method of treatment in patients without clotting problems. PMID- 1607082 TI - Percutaneous endoscopic gastrostomy for decompression of the stomach and small bowel. AB - Percutaneous endoscopic gastrostomies are used most commonly for enteral feeding. We report the use of such gastrostomies for decompression of the obstructed gastrointestinal tract. Percutaneous endoscopic gastrostomies were performed on 53 patients over a 2-year period for gastrointestinal decompression because of gastric or small bowel obstruction. Forty-six patients had malignant obstruction from a primary abdominal or metastatic carcinoma and 7 patients had non-malignant obstruction or stasis. Gastrostomy for decompression was successful in 41 of 46 (89%) cases of malignant obstruction and in all 7 of the non-malignant cases. Tube utilization for decompression averaged 60 +/- 91 days. A 28 F tube with a 4 inch perforated intragastric portion was fashioned to maximize drainage. This efficient decompression tube allowed oral intake of liquids and soft foods in 88% of patients. Complications, which occurred in 4%, included one case of fatal peritonitis and one case of cellulitis. PMID- 1607083 TI - Upper gastrointestinal endoscopy: a prospective randomized study comparing continuous supplemental oxygen via the nasal or oral route. AB - We have examined the efficacy of supplemental oxygen in preventing episodes of significant arterial desaturation (SpO2 less than 90%) during upper gastrointestinal endoscopy. We have compared the effects of 2 liters.min-1 of oxygen given orally via the bite-guard with the same flow rate via nasal cannulas and have also examined the effects of pre-oxygenation. Results of this study at a flow rate of 2 liters.min-1 have been compared with previously published results at a flow rate of 3 liters.min-1. Although in this study fewer episodes of desaturation were seen in the orally supplemented group compared with the nasal group, the difference observed was not statistically significant. Pre-oxygenation significantly reduced episodes of desaturation (SpO2 less than 90%, p less than 0.01) and prevented SpO2 falls below 85% in all patients studied. Supplemental oxygen given at a rate of 2 liters.min-1 was as effective as that given at a rate of 3 liters.min-1 in preventing significant desaturation, as previously defined, during the procedure. We therefore recommend the use of supplemental oxygen at a flow rate of 2 liters.min-1 in all high risk patients and conclude that the oral route has practical advantages and is at least as effective as nasal cannulas. PMID- 1607084 TI - The near-infrared electronic endoscope for diagnosis of esophageal varices. AB - We developed an electronic endoscope sensitive to light delivered by an infrared laser, which makes it possible to visualize submucosal vessels of the gastrointestinal tract. The system consists of a modified electronic endoscope and an image processing unit. A high output laser diode was chosen as the source of the infrared ray with a wavelength of 815 nm, an output of 200 milliwatts, and a band width of 30 nm. Using this instrument, esophageal varices were classified into three categories: venous dilation, dark spot, and diffuse dark area. The venous dilation and dark spot appearances correlated with early esophageal varices, which were rarely seen with visible light. On the other hand, the diffuse dark area appearance was considered to be a high risk sign of future bleeding. This system is useful not only for the early diagnosis of esophageal varices, but also for the localization of optimal puncture sites and the evaluation of the effect of sclerotherapy. PMID- 1607085 TI - Bacteremia after endoscopic band ligation of esophageal varices. AB - In a 6-month period, 17 consecutive unselected patients undergoing emergency or elective endoscopic variceal band ligation were evaluated prospectively for clinical and bacteriological signs of bacteremia after each treatment session. None had signs of sepsis, fever, or chills; however, in one patient, a coagulase negative Staphylococcus epidermidis was cultured from peripheral blood at 5 but not 30 min after the procedure. These data indicate that, in contrast to sclerotherapy, endoscopic variceal ligation rarely induces bacteremia. PMID- 1607086 TI - Decreased bacterial adherence to silver-coated stent material: an in vitro study. AB - Bacteria are important in causing biliary stent blockage through adherence and subsequent biofilm formation. In our in vitro system, surface modification using test polyurethane discs with silver coating led to a reduction in the number of adherent bacteria compared with untreated controls by 10- to 100-fold in an apparently dose-related manner. The effect was more marked in the presence of bile. These results suggest that silver coating may have a potential benefit in preventing stent blockage. PMID- 1607087 TI - Incidence and risk factors for biliary and pancreatic stent migration. AB - Endoprostheses are commonly used in the treatment of biliary and pancreatic disorders. The frequency of and potential risk factors for stent migration, however, remain largely unknown. From January 1986 to June 1990, 807 biliary and pancreatic stents were placed at our institution. Our study analyzed the occurrence of stent migration among the 589 stents for which follow-up data were available. Results demonstrated incidence rates of 4.9 and 5.9% for proximal (into the duct) and distal (out of the duct) biliary stent migration, respectively. Likewise, incidence rates of 5.2 and 7.5% were observed for proximal and distal pancreatic stent migration, respectively. Malignant strictures, larger diameter stents, and shorter stents were significantly associated with proximal biliary stent migration. Sphincter of Oddi dysfunction and longer stents were associated with proximal pancreatic stent migration. Migration of stents out of the common bile duct occurred more frequently in papillary stenosis. No other significant risk factors for distal migration were found. These results indicate that stent migration is an important complication. Multiple risk factors were associated with stent migration and need to be considered in the development of new stent types. PMID- 1607088 TI - The effects of applied pressure on the thickness, layers, and echogenicity of gastrointestinal wall ultrasound images. AB - Endoscopic ultrasound imaging of the gastrointestinal wall can be performed through intraluminal fluid or by direct transducer contact with the wall. We tested the hypothesis that the ultrasound appearance of the gastrointestinal wall is influenced by the amount of pressure applied when the transducer is in contact with the tissue. Fresh autopsy specimens from the porcine gastrointestinal tract were examined in vitro using an 8.5-MHz linear array ultrasound system. As transducer pressure against the wall was increased from 0 to 10 KPa, changes were seen on the images in wall thickness, tissue echogenicity, and the number of layers. The stomach and rectum were more resistant to compression than the esophagus, duodenum, and colon. Wall echogenicity increased with increasing degrees of applied pressure and some layers were obliterated by this pressure. The second ultrasound layer, or deep mucosa, appeared to be the most susceptible to compression. Endoscopic ultrasound imaging artifacts should be reduced by limiting the amount of pressure applied to the wall with the transducer. PMID- 1607089 TI - Symptoms, gastritis, and Helicobacter pylori in patients referred for endoscopy. AB - Acute Helicobacter pylori infection is associated with dyspeptic symptoms but chronic infection has not clearly been shown to cause symptoms. To define further the role of H. pylori infection and gastritis in dyspepsia, we interviewed all patients about to undergo upper endoscopy, recorded the primary indication for endoscopy, noted the endoscopic findings, and obtained antral biopsies. Among non ulcer patients there was a strong correlation of acute gastritis with H. pylori. Gastritis and H. pylori increased with age, and non-steroidal anti-inflammatory drug use correlated with normal histology. Neither H. pylori concentration nor gastritis grade correlated with gender, use of alcohol and tobacco, indication for endoscopy, or symptoms (epigastric pain, nausea, vomiting, bloating, belching, heartburn, halitosis, and flatulence). PMID- 1607090 TI - Gastric acid secretion, parietal cell sensitivity, and endoscopic characteristics of duodenal ulcer patients with and without stigmata of recent bleeding. AB - Duodenal ulcer patients with stigmata of recent hemorrhage are at high risk of rebleeding. Whether the acid secretory capacity, the parietal cell sensitivity and endoscopic characteristics are different in patients with and without stigmata of recent hemorrhage are unclear. To investigate these, we studied 885 patients with active duodenal ulcer. Among them 693 patients presented with pain only and the rest with gastrointestinal bleeding. Within the latter group, 135 patients had no or minor stigmata (i.e., flat spot) of bleeding while 37 patients had major stigmata of bleeding (i.e., visible vessel and visible clot). The basal acid output and gastric acid output in response to infusion of graded doses of pentagastrin from 93.8 to maximal dose of 6000 ng/kg.hour (maximal acid output) were measured. The dose of pentagastrin required for half maximal response to gastric acid output was taken to represent the sensitivity of the parietal cells to pentagastrin (D50c). The results demonstrated that the basal acid output, maximal acid output, and D50c were not significantly different among the three groups. Endoscopically the size and site of the ulcer were similar, but patients with major stigmata of bleeding had significantly higher degrees of duodenal inflammation and deformity. We conclude that gastric acid secretion and D50c were not significantly different in patients with major and minor stigmata of recent bleeding, indicating that gastric acid may not play a significant role in precipitating gastrointestinal bleeding. PMID- 1607092 TI - Chromoscopy of the colon using indigo carmine dye with electrolyte lavage solution. PMID- 1607091 TI - Addition of enemas to oral lavage preparation for colonoscopy is not necessary. AB - To evaluate whether the addition of enemas to oral electrolyte lavage is helpful for colonoscopic preparation, we conducted a prospective, randomized, observer blinded trial to compare oral lavage plus enemas with oral lavage alone. The quality of preparation, mucosal visualization, and the volume of retained colonic fluid did not differ between the two groups. Twenty-two percent of the patients in the group who received oral lavage plus enemas compared with 12% of the patients in the group that only received oral lavage stated that they would refuse to repeat the preparation for future colonoscopic examination. Seventeen percent of the patients in the group that received oral lavage plus enemas demonstrated anorectal trauma or inflammation compared with only 5% in the group that received oral lavage alone (p = 0.09). These results indicate that the addition of enemas to oral lavage preparation for colonoscopic evaluation cannot be routinely recommended. However, enemas may be considered on an individual basis in the occasional patient unable to consume the complete oral lavage or in whom residual stool is found during colonoscopic evaluation after oral lavage preparation. PMID- 1607094 TI - Choledocholithiasis and a double gallbladder. PMID- 1607093 TI - Endoscopic retrograde ileography. PMID- 1607095 TI - Non-traumatic intrahepatic rupture of the biliary tree with biloma: the place of ERCP. PMID- 1607096 TI - Endosonography in the pre-operative diagnosis of choledochocele. PMID- 1607097 TI - Bacterial meningitis occurring after esophageal dilation in an otherwise healthy patient. PMID- 1607098 TI - Colonic strictures in a patient on long-term non-steroidal anti-inflammatory drugs. PMID- 1607099 TI - Endoscopic demonstration of non-steroidal anti-inflammatory drug-induced small intestinal strictures. PMID- 1607100 TI - Polyps large and small. PMID- 1607101 TI - Databases for gastrointestinal endoscopy. PMID- 1607102 TI - PEG tube removal and steroids. PMID- 1607103 TI - Gastric ulceration following PEG replacement. PMID- 1607104 TI - Simplified method of endoscopic PEG replacement. PMID- 1607105 TI - A safety maneuver for placing overtubes during endoscopic variceal ligation. PMID- 1607107 TI - Chronic light damage to the macula of an endoscopist. PMID- 1607106 TI - Urticarial reaction to oral polyethylene glycol electrolyte lavage solution. PMID- 1607108 TI - Minimally invasive therapy. PMID- 1607109 TI - Patriotic swallow. PMID- 1607110 TI - Long term results of choledochoduodenostomy in the treatment of choledocholithiasis. PMID- 1607111 TI - Endoscopic sphincterotomy: the whole truth. PMID- 1607112 TI - [Surgical treatment of invasive malignancies of the vulva using CO2 laser]. AB - In a retrospective study, we analysed 26 CO2-laser vulvectomies within the observation period between 1982 and 1990. Indications for vulvectomies were invasive malignancies of the vulva, FIGO stage I to III. 91.7% were squamous cell carcinomas. The mean age of patients was 69.3% (43 to 87) years. Five radical local excisions, one modified radical vulvectomy and in all other cases radical vulvectomy was performed. Laser surgery of the vulva was combined with bilateral lymphadenectomy or radiotherapy of inguinal lymph nodes. If necessary, a gluteal rotation flap was built to achieve closure of the wound without tension. No serious intra- or postoperative complications were observed, wound breakdown with per secundam healing as the most common complication occurred in 29.1%. Functional and cosmetic results were examined in a detailed follow-up at least 12 months postoperatively, showing promising results (56.3% good, 37.5% satisfactory, 6.3% unsatisfactory). The surgical procedure, perioperative management, recurrence rate (3 patients, 12.5%), as well as functional and cosmetic results, are presented and discussed in detail. The use of CO2-laser in surgical treatment of vulvar malignancies improves cosmetic and functional results. This is important, particularly with regard to the increasing number of young women with vulvar neoplasia. PMID- 1607113 TI - [Inflammatory cancer of the breast. Therapy and follow-up]. AB - Inflammatory carcinoma has the highest mortality rate amongst the locally progressed cancers of the female breast. To define it, clinical, pathological and biological criteria have to be considered. The crucial finding is tumour-cell embolism in the subdermal lymphatics of the affected breast. 30 patients with inflammatory breast cancer were treated with three different concepts of therapy. In the first group, initial surgery (mastectomy with axillary dissection) was followed first by 6 cycles of chemotherapy, then by radiation of the thoracic wall, axilla and supraclavicular lymph nodes. The second concept included primary chemotherapy (6 cycles) with mastectomy/axillary dissection after the second or third cycles. In the third group, primary radiation of breast and axilla was performed, followed by 6 cycles of chemotherapy. From all three groups, 9 patients showed receptor-positive tumours; additional tamoxifen therapy (if postmenopausal) or GNRH-analogues (if premenopausal) were given. None of the three therapy managements could improve the average time of survival. Only the patients with hormonal therapy showed a better prognosis, which might well have been the result of a higher differentiation of the tumour. The study proves, that our efforts in therapy have so far been insufficient. Mastectomy, in particular as a psychically traumatizing procedure, fails to improve the patient's prognosis. It might regain its importance, when new, satisfactory methods of therapy of the systemic disease "inflammatory breast cancer" have been found. It is still uncertain, whether better prognosis can be achieved by a treatment with GNRH-analogues. PMID- 1607114 TI - [Complications of radical operation of uterine cancer. Closure of the peritoneal defects--yes or no?]. AB - The case reports of 70 patients (including 12 cases of endometrial carcinoma operated by the same method) were evaluated for postoperative complications such as pathological changes in the iv-pyelograms, incidence of haemorrhage or haematomas at the operation site, and for the frequency of lymphatic cysts. In addition, the amount of secretion and the duration of drainage were recorded. In 26 patients, the wounds of the parietal peritoneum were sutured, in 44 women, the pelvic peritoneum was left open after primary occlusion of the vaginal vault. If the two groups are compared with respect to the incidence of complications, the results are: pathologic postoperative ivP: 3.4:1; haemorrhage or haematomas: 5:1; lymphatic cysts: 1.6:1. The duration of drainage was almost the same in both groups (1.1:1), but the amount of liquid drained was less in the peritonealised group (0.5:1). These data and the fact, that the overall morbidity in the "open peritoneum" group was significantly lower, leads us to recommend strongly that leaving the pelvic peritoneum open provides evident advantages compared with the traditional procedure. In addition, a marked reduction of the operation time is achieved. Negative consequences, such as postoperative ileus, did not occur. PMID- 1607115 TI - [Hysteroscopic resection of submucous myoma]. AB - Between 1988 and 1991, 39 patients with intrauterine submucous fibroids were treated at the University of Dusseldorf, Department of Gynaecology and Obstetrics, by hysteroscopic resection. Myoma diameter ranged from 1 cm to 6 cm with a median of 2.6 cm. 29 patients had bleeding problems in form of meno metrorrhagia; 14 patients suffered from infertility, 2 patients were treated by combined transabdominal-transcervical approach because of multiple myomata. One severe intraoperative complication occurred as an uterine perforation with injury to the small bowel. No other complication was seen. All patients with bleeding problems returned to normal menses after the operation. Four women became pregnant, one had an early abortion, one an ectopic pregnancy, two women delivered at term. Hysterectomy could be avoided in all cases. PMID- 1607116 TI - [Histologic placenta findings in diastolic zero or negative flow of the umbilical arteries: a prospective study with reference to the duration of clinical observation]. AB - 37 cases with enddiastolic zero flow or reverse flow (dZRF) in the umbilical arteries were compared with 37 gestational age-matched controls. In dZRF the placenta is significantly smaller (weight and basal area) throughout the entire gestational age. Vascularisation of the villous tree is often reduced in cases with dZRF, but the findings are not uniform. However, there is a direct interdependence of the histologic findings of villous maturation, terminal villus deficiency, reduced vascularisation and endangiopathia obliterans from the duration of clinical observation. The longer the control period was, the higher was the amount of accelerated villous maturation, angiosis of terminal villous vessels, less endangiopathia obliterans, with simultaneously improved foetal outcome. We conclude from these data, that the main placental lesion, which may cause dZRF, is located in the central villous tree and vascular tree, which is possibly related to the smallness of the placenta, whereas the changes in the terminal villi may exercise compensatory functions and may influence foetal outcome. PMID- 1607118 TI - [Placental findings in "vanishing twins"]. AB - We examined morphologically the placenta in 15 cases of a "vanishing-twin" phenomenon of early pregnancy sonographically confirmed. In 10 of these cases remnants of an additional gestation product could be identified with ample variation in their conservation. These ranged between macerated, but clearly identifiable foetal residues and morphologically regular, empty gestational sacs, all being localised at the placental margin or within the amniotic tissue sheets. The chorionic villi of the surviving twins were normally developed. There was no evidence of any correlation between the developmental status of the vanished twin and any therapeutical intervention, age of the mother or number of initial gestational products. In 3 cases, an intrauterine foetal reduction by foetocide had been performed. In these instances, rather well-developed remnants of the additional fetuses could be found. Since in all cases a pluri-chorionic placenta was present, it is possible, that the vanishing twin phenomenon may be held responsible for an eventual blood group incompatibility during subsequent pregnancies. PMID- 1607117 TI - [Amniocentesis in prenatal diagnosis for psychological reasons]. AB - By means of a questionnaire and three personality tests, we investigated, whether there were any differences in the personality structure between patients who underwent an amniocentesis because of psychological indications, and a matched pair group of pregnant woman without amniocentesis. The results of the personality inventories showed no significant differences in the personality structure between both groups of pregnant women. In particular, they showed no difference with respect to the anxiety factor. As a result of our questionnaire we can state, that factors like education, the handicapped child in the environment, profession and the lack of commitment to bring up a handicapped child, influence the decision to undergo an amniocentesis. PMID- 1607119 TI - [Treatment of primary therapy refractory choriocarcinoma using the EMA-CO protocol]. AB - This is a report on a 33 year old patient with a metastatic gestational choriocarcinoma. The patient was hospitalized with the picture of a spontaneous left kidney rupture and nephrectomy was performed. Under primary mono-dose methotrexate chemotherapy, the patient showed rapidly progressive metastases in both lungs, liver, right kidney and soft tissue. With the use of multiple chemotherapy, according to the EMA-CO scheme, we observed complete remission. To date, there has been no indication of any tumour recurrence. PMID- 1607120 TI - [Struma carcinoid tumor within a dermoid cyst as an incidental finding in cesarean section]. AB - A 25-year-old primigravida with breech presentation was admitted near term. During Caesarean section, a dermoid cyst of the right ovary was detected. The dermoid cyst was enucleated, preserving a plum-sized ovary. Histology revealed a strumal carcinoid within the excised dermoid cyst. From the histological point of view it was classified as a tumour of low malignancy. The clinical study provided no evidence of any metastases. On the 14th postoperative day the patient could be discharged from hospital subject to close aftercare control. PMID- 1607121 TI - [Fetomaternal macrotransfusion after successful internal version from breech presentation by moxibustion]. AB - In a primigravida with a fundal/anterior wall placenta, a successful cephalic version was noted at 39 weeks after repeated moxibustion of the point Zhiyin (bl 67). Since routine foetal heart rate monitoring showed a sinusoidal pattern with severe decelerations, immediate Caesarean section was performed. Foetomaternal macrotransfusion of about 300 ml of blood was found. In view of this complication, possible risks of the method are discussed. Moxibustion does not seem to be suitable as self-therapy without close medical follow-up. PMID- 1607122 TI - [Rational hormone diagnosis?]. PMID- 1607123 TI - [Rational hormone diagnosis in normocyclic functional sterility]. PMID- 1607124 TI - Trigeminal neuralgia and "SUNCT" syndrome: similarities and differences in the clinical pictures. An overview. AB - SUNCT is a recently described unilateral headache with frequently occurring, shortlasting pain attacks in the ocular area accompanied by ipsilateral conjunctival injection, lacrimation, and (subclinical) forehead sweating. In some patients, attacks may be triggered by cutaneous stimuli. In this communication, SUNCT patients (n = 5) are compared with the considerable clinical series of trigeminal neuralgia in the literature (e.g. Harris, 1940, 1433 cases). In several respects (unilaterality, triggering, brevity and frequency of paroxysms), SUNCT shows similarity to trigeminal neuralgia. SUNCT seems to differ clearly from trigeminal neuralgia in other respects: sex distribution (SUNCT patients are often males), pain localization (SUNCT patients have the pain in the ocular area), the carbamazepine effect, presence of conjunctival injection, lacrimation, etc. SUNCT may accordingly altogether seem to be distinct from trigeminal neuralgia. PMID- 1607125 TI - Sympathetic adrenomedullary activity in cluster headache. AB - It is well known that autonomic phenomena, such as lacrimation, rhinorrhea, and Horner's syndrome, are associated with the pain attacks in episodic cluster headache. In order to elucidate the cause of these symptoms we studied plasma free and sulphoconjugated catecholamines in cluster headache patients during the pain attacks and in the following hours, as well as during the remission period. No change in these amine levels was found. We conclude that dysautonomic symptoms are not reflected in plasma catecholamine modification. PMID- 1607126 TI - Autonomic diabetic neuropathy: skin sympathetic response and neurovegetative cardiovascular functionality tests. AB - One hundred and twelve diabetic patients were submitted to several tests for evaluation of autonomic cardiovascular and sudomotor function. It was found that a patient could be positive to one test and negative to others, thus confirming the presence of sectorial lesions which do not affect the autonomic nervous system uniformly. The parasympathetic system is more frequently and precociously affected than the sympathetic system. The tests used for investigating the sympathetic component, the sympathetic skin response (SSR) gives results which are more frequently and precociously altered. PMID- 1607127 TI - N omega-nitro-L-arginine-methyl ester inhibits electrocortical recovery subsequent to transient global brain ischemia in Mongolian gerbil. AB - Electrocorticographic (ECoG) activity remains isoelectric for about 15 min after transient (10 min) bilateral carotid arteries occlusion in mongolian gerbils. In this model of global forebrain ischemia N omega-Nitro-L-arginine methyl ester (L NAME), a nitric oxide (NO) synthase inhibitor, significantly delays the recovery of ECoG amplitude. Thus, the present experiments suggest that NO is involved in the cerebrovascular physiological response to brain ischemia. PMID- 1607129 TI - [ras oncogene-related small molecular weight GTP-binding protein, rho gene product and botulinum C3 ADP-ribosyltransferase]. AB - The ras oncogene products (ras p21s) are 21-KDa proteins with activities of GTP binding and hydrolysis. A number of proteins homologous to ras p21 have been discovered and collectively named small molecular weight GTP-binding proteins. These proteins undergo post-translational modification with isoprenoid residues attached to cysteine in their carboxyl terminal. With this modification, they attach to cellular membranes. The biochemical activities of these proteins, i.e., GTP hydrolysis and binding, are regulated by various regulatory factors such as GDP-GTP exchange proteins and GTPase-activating proteins, but little is known about the cellular functions and physiological pathways through which they regulate these functions. Botulinum C3 ADP-ribosyltransferase, a 23-KDa exoenzyme secreted from certain strains of types C and D Clostridium botulinum, specifically ADP-ribosylates the rho family of these GTP-binding proteins. This ADP-ribosylation occurs at a specific asparagine residue in their putative effector domain, and presumably interferes with their interaction with a putative effector molecule downstream in signal transduction. C3 exoenzyme, when incubated with or microinjected into cultured cells, ADP-ribosylates a rho gene product in the cells, and causes profound cell rounding with loss of adhesion plaques and collapse of stress fiber. Microinjection of an activated mutant of rho A protein, on the contrary, induced extensive adhesion and actin assembly in cultured cells. These results suggest that the rho family of proteins are involved in morphogenesis and motility of cells via assembly and disassembly of cytoskeletal systems, and botulinum ADP-ribosyltransferase is a useful tool for clarifying the molecular mechanism of these processes. PMID- 1607128 TI - Interleukin-1 beta and interleukin-6 mRNA are expressed in human glioblastoma and neuroblastoma cells respectively. AB - We report the expression of different interleukins (IL) in four human glioblastoma and neuroblastoma cell lines. The glioblastoma cell line LI, expresses IL-1 beta and IL-6 mRNA, though not IL-2 and IL-4. The expression of the former gene is modulated by retinoic acid. Two cell clones [BE(2)-C and BE(2) M17] as well as the neuroblastoma cell line SK-N-BE(2), from which both clones were derived, express IL-6 mRNA, but not IL-1 beta, IL-2 or IL-4. Both IL-1 beta and IL-6 cytokines are known to increase hypothalamic CRH mRNA, a gene reported to be expressed in all these cell lines. The production of both cytokines and neuropeptides indicates a complex dialogue between tumour cells and anti-tumour immunity. PMID- 1607131 TI - [Pharmacodynamics and therapeutic usage of recombinant human erythropoietin (SNB 5001) in animal models]. AB - In mice, SNB-5001 released reticulocytes dose-dependently. In rats, rabbits and dogs given the same doses of SNB-5001, each dose-response curve of hemopoiesis almost showed parallelism. SNB-5001 induced nearly the same extent of hemopoiesis in these animals. After the hemopoiesis caused by SNB-5001, reticulocytes decreased within a week in both rats and dogs, but numbers of red blood cells (RBC) were higher than each control group for over 2 weeks in rats and for over 3 weeks in dogs. In polycythemic rats given excessive doses (200-5000 U/kg) of SNB 5001, blood volume increased, but blood pressure did not change. In the renal anemic rats produced by partial nephrectomy, dose-related and cumulative hemopoiesis were observed in both groups given SNB-5001 with different administration schedules (once a day for a week or once a week for 3 weeks). In the phrebotomized rats, SNB-5001 accelerated the recovery from the anemia induced by phrebotomy when given in a large quantity (6 ml/rat) and prevented the progressive anemia induced by intermittent phlebotomies when given in a small quantity (1 ml/rat x 3). SNB-5001 also improved the anemia caused by chronic inflammation in rats. However, increases of hemoglobin and hematocrit were smaller than that of RBC. Those results were caused by impaired release of iron from the reticuloendothelial system. PMID- 1607130 TI - [Effects of partial nephrectomy on the pharmacokinetics and pharmacodynamics of recombinant human erythropoietin (SNB-5001) in rats]. AB - The present study examined the pharmacokinetic and pharmacodynamic profiles of recombinant human erythropoietin (SNB-5001) in partially nephrectomized rats. The plasma level of SNB-5001 was measured by a 2-step enzyme immunoassay. The plasma disappearance curve after intravenous injection of SNB-5001 (50 U/kg) in these rats showed a biexponential pattern similar to that in non-treated rats, conforming to a two-compartment model. However, the total body clearance was reduced, the plasma half life was prolonged and the area under the concentration time curve of SNB-5001 was increased by the partial nephrectomy. The distribution volumes of SNB-5001 were almost the same as those in non-treated rats. It is suggested that the kidney may contribute to the elimination of SNB-5001. Dose dependent increases of reticulocytes, red blood cells, hemoglobin and hematocrits were observed after seven repetitive intravenous injections of SNB-5001 in both partially nephrectomized rats and non-treated rats. Hemopoietic responses were calculated by subtracting the initial values from the values after SNB-5001 injections of each hematological parameter (reticulocytes, red blood cells, hemoglobin and hematocrits). Hemopoietic responses in partially nephrectomized rats were apparently stronger than those in non-treated rats. These results suggest that the reduction of clearance by the partial nephrectomy may contribute to the hemopoietic responses, in addition to suggesting that the uremic conditions do not inhibit the effects of SNB-5001 in partially nephrectomized rats. PMID- 1607132 TI - [Protective effects of naftidrofuryl oxalate against hypoxia-induced death]. AB - To analyze the effects of naftidrofuryl oxalate (LS-121) on the central nervous system exposed to critical hypoxia, survival duration was employed as a parameter of the protective effects of the drug against hypoxia-induced death. In the control group (no drug administration), the electroencephalogram (EEG) was flattened promptly after changing to hypoxia from aerobic conditions, and it was impossible to recognize precisely what time the EEG disappeared because of vigorous body movements. Arterial blood pressure (BP) was clearly recognized, and rats never recovered after BP decreased to 0 mmHg, although the electrocardiogram (ECG) was still recorded. Thus, survival duration recognized by measuring the time from the onset of hypoxia to the time when BP became 0 mmHg was considered to be a good indicator. After LS-121 (10 mg/kg) administration, survival duration was significantly prolonged compared to the control. Combination therapy of LS 121 (25 mg/kg) and bifemelane hydrochloride (BI) (25 mg/kg) also revealed the prolongation of survival duration. Neither idebenone (10 mg/kg) nor nicergoline (10 mg/kg) showed significant changes in survival duration. These findings suggest that LS-121, either with or without BI, could improve cerebrovascular disorders induced by hypoxia. PMID- 1607133 TI - [The gastric mucosal adhesiveness of Z-103 in rats with chronic ulcer]. AB - The gastric mucosal adhesiveness of Z-103 in rats with acetic acid ulcer was studied macroscopically, histologically, and biochemically. From macroscopical observations, when Z-103 was orally administered to an acetic acid ulcer model, there was adhesion of Zn to the normal mucosa as well as the ulcerous site under both the fasting condition and after feeding. It was also proven that the strength and duration of adhesiveness were increased dose-dependently under fasting conditions. In addition, histological localization of Zn was noted from the covering epithelial cell layer to the gastric lamina propria mucosae in the normal tissue and in the most superficial ulcerous layer and the granulous layer of the ulcerous site. Measurement of the gastric tissue Zn content after oral administration of 100 mg/kg of Zn showed that the Zn content was significantly increased for 6 hr at the normal site and for 24 hr at the ulcerous site. On the other hand, although ZnSO4 and ZnSO4+carnosine combination macroscopically produced generally the same level of adhesiveness as Z-103, when the gastric tissue Zn content for Z-103 and ZnSO4 were compared, the Zn content of ZnSO4 was lower than that for Z-103 at both the normal and ulcerous site. In summary, Z-103 shows a long-term adhesive and permeable action on the gastric mucosa in acetic acid ulcer rats, and it has a comparable high affinity at the ulcerous site. PMID- 1607134 TI - [AIDS> Misgivings about wonder "vaccine". Function of the immune system--study without controls]. PMID- 1607135 TI - [Growth hormone therapy in childhood. Certain indications]. AB - The diagnosis of growth hormone deficiency is established on the basis of auxological and endocrinological studies. Without treatment, the final stature will be reduced; by way of treatment, administration of biosynthetic human growth hormone is required. Total and partial growth hormone deficiency can be distinguished, as also neurosecretory dysfunction of growth hormone secretion. Growth hormone can also be successfully administered to girls with the Ullrich Turner syndrome, but the doses required are somewhat higher than in the case of growth hormone deficiency. Other forms of reduced stature might possibly benefit from growth hormone treatment, but the results of ongoing studies on this point must first be obtained. PMID- 1607136 TI - [Growth hormone therapy in adulthood]. AB - Only a few controlled studies on replacement therapy with growth hormone (GH) in adults have been published. These studies have demonstrated that GH leads to an increase in muscle mass and a decrease in fatty tissue. In addition, there is an improvement in renal and cardiac function. To date, there has been only a single study demonstrating the efficacy of pharmacotherapy with growth hormone in the elderly. Again, an increase in muscle and bone mass, and a decrease in fat mass, an increase in skin thickness, and an improvement in overall wellbeing was reported. Although these studies do not unequivocally demonstrate the benefit of GH treatment, they are interesting enough to warrant further studies on replacement therapy, and also on pharmacotherapy with growth hormone. PMID- 1607137 TI - [Neuroendocrine tumors of the gastrointestinal tract. 1: Clinical aspects]. AB - Endocrine cells are characterized by common biochemical properties and specific cellular markers. Endocrine tumors, too, differ from other types of tumor in a number of ways. These have to do with the classification, the occurrence of functioning or nonfunctioning forms, benign and malignant courses, solitary or multiple presentation, as well as entopic and ectopic growth forms. The incidence of the gastrointestinal functioning tumors is about 0.5-1.0 per 100,000, the nonfunctioning tumors predominating many times over. The diagnosis of functioning endocrine tumors in the early phases of the disease is based on the biochemical demonstration of substances released into the blood, and the clinical picture is determined not primarily by the size or extent of the tumor, but by the biological effects of the tumor secretions. The clinical symptomatology associated with these tumors is often much more marked than the measurable tumor manifestation. PMID- 1607138 TI - [Digital luminescence radiography in the framework of ERCP. Initial results in comparison to conventional radiography]. AB - Forty-seven patients submitted to an ERCP were submitted, in one and the same session, to radiological examination with both conventional and digital luminescence radiography (DLR). Within the framework of this orientational study, DLR provided at least the same amount of information as the conventional examination, but was also associated with diagnostic advantages in particular in the region of the intrahepatic bile ducts and in the representation of a cholelithiasis. PMID- 1607139 TI - [Current chemotherapy in urogenital infections. 6: antibiotics during pregnancy and lactation in urethro-adnexitis, vulvovaginitis and cervicitis]. PMID- 1607140 TI - [Venous tonicity in pregnancy varicose veins]. AB - The dilation of the femoral vein during pregnancy was analysed retrospectively in patients with unilateral severe varicose veins (group I, n = 7), mild varicose veins (group II, n = 8) and healthy pregnant women (group III, n = 3). Groups I and II employed elastic stockings as treatment, while group I additionally applied a ruscus-containing cream to the affected leg. In the healthy women, in the unaffected leg in group II and in the cream treated leg in group I, the femoral vein increased in diameter on average by 2.1 to 2.4 mm in the third term of pregnancy, while in the affected leg of group II it increased by 3.6; in group I the increase in the leg not treated with cream was about 4.5 mm. The differences in dilatation are significant (p less than 0.05). Apparently, the venous tonic action of ruscus extract can considerably reduce venous dilatation during pregnancy. PMID- 1607141 TI - [Sphingolipidosis]. PMID- 1607142 TI - Holter ECG recordings before and after surgical treatment of hyperthyroidism: circadian pattern of heart rate and arrhythmias. AB - Holter ECG recordings obtained form 11 hyperthyroid patients (mean age 29.2 +/- 11.4 years) before and after surgical treatment were analyzed regarding heart rate (HR) and arrhythmias. The mean 24-hour HR significantly decreased form 104 +/- 8.8 bpm before to 76.8 +/- 8.9 bpm after the treatment (p less than 0.001), with the most pronounced reduction while asleep form 0:00 AM to 6:00 AM. HR variability also significantly decreased (p less than 0.02), but the circadian rhythm of HR did not change before and after the treatment. Serum T3 level correlated with the mean HR (r = 0.63, p less than 0.05) in hyperthyroid state. The percent changes in T3 (% delta T3) best correlated with the percent changes in the mean HR (% delta mean HR) (r = 0.84, p less than 0.01). The frequencies of supraventricular and ventricular premature contractions significantly decreased after the surgical treatment (p less than 0.01). Normal circadian pattern of hourly HR before the treatment highly suggests that normal adrenergic responsiveness is maintained in hyperthyroidism. PMID- 1607143 TI - Anticariogenic effects of green tea. AB - The effects of green tea extract on caries inhibition of hamsters and on acid resistance of human tooth enamel have been investigated. Both in vivo and in vitro experiments showed that original extract of green tea had the significant effects on these points. The dialyzed tea solution in which the fluoride was removed almost completely, also showed the remarkable effects both in vivo and in vitro experiment as is similar to the original tea extract. The results obtained from this study suggested that fluoride in green tea may play a role to increase the cariostatic action in cooperation with other components in tea. However, the action of fluoride does not seem to be so important, because its concentration is very low. The effect of green tea on caries inhibition as well as on the increment of acid resistance appears to be more correlative with the non dialysable substances in tea. PMID- 1607144 TI - [A case of hyporeninemic hypoaldosteronism improved by dexamethasone treatment]. AB - A 76-year-old man was admitted because of general fatigue and lumbago. Two years before admission, hyponatremia and hyperkalemia were pointed out, subsequently hydrocortisone (20 mg/day) was given under the diagnosis of panhypopituitarism. The marked improvement was found in the electrolytes abnormality. On examination at admission, there was no abnormality of anterior pituitary function. In addition to the extremely low level of plasma renin activity and aldosterone concentration, the persistent microhematuria and hyperuricemia were found, however, renal histology only showed the benign arteriosclerosis but no significant alteration in juxtaglomerular apparatus and glomeruli. The urinary prostacyclin metabolite output was rather increased compared to that of normal subject, suggesting that prostaglandins may not be responsible for the defect of renin secretion. Although, the cause was still unknown, small dose of dexamethasone was extremely effective to resolve electrolytes abnormality and hematuria. PMID- 1607145 TI - Compared plasma and brain pharmacokinetics of clomipramine and its metabolite demethylclomipramine in two strains of mice (NMRI and CD1). AB - The fate of clomipramine (CMI) and its main demethylated metabolite demethylclomipramine (DCMI) was studied in two strains of Swiss mice (NMRI and CD1) after intraperitoneal injection. A study of its distribution among various tissues showed that fixation was most marked in lungs, perirenal fat and kidneys, and only moderate in the brain. The pharmacokinetic parameters of both molecules were determined in brain tissue and plasma. Absorption was rapid (tmax CMI = 14 min), metabolism prompt (tmax DCMI = 17 or 18 min according to the breed) and elimination rapid from both plasma and brain tissue. The first two stages were similar in the two strains, but elimination of CMI from both plasma and brain was faster in the NMRI mice (plasma t1/2 = 53 min against 165 min in the CD1 mice). Both values were well below that reported for man (mean plasma t1/2 = 24 h). The data presented can serve as a basis for designing true chronic administration protocol in animals. PMID- 1607146 TI - Comparative effects of different uptake inhibitor antidepressants in two pain tests in mice. AB - The purpose of this study was to compare the analgesic effect of acute injections (1.25 and 20 mg/kg, ip) of several antidepressants with different effects on monoamine reuptake, on two pain tests in mice (hot-plate and phenylbenzoquinone induced abdominal writhes). Serotonergic inhibitors (citalopram, fluvoxamine and clomipramine) were more effective in the hot-plate test whereas noradrenaline reuptake inhibitors (desipramine and maprotilline) were more effective in the writhing test. The mixed antidepressants (amitriptyline and to a lesser degree trimipramine) were more effective in the two tests than the other antidepressant drugs. Changes in motor activity of clomipramine and amitriptyline could not account for the modifications of pain threshold. Amineptine (a dopamine reuptake inhibitor) failed to induce any antinociceptive effect in the hot-plate test and was hyperalgesic in the writhing test, which could be explained by an increased motor activity. These findings indicate that the antinociceptive potency of reuptake inhibitors varies according to their monoamine specificity and the nature of stimuli. They would suggest that the preferential choice of serotonergic antidepressants in the management of chronic pain is arguable. PMID- 1607147 TI - Rapid changes in 3H-imipramine platelet binding after chronic treatment with amineptine, a selective dopamine uptake blocker, in major depressed patients. AB - The effect of chronic treatment with amineptine (200 mg daily), a tricyclic antidepressant drug selectively blocking dopamine uptake, on 3H-imipramine binding, was investigated in platelets of major depressed patients in conjunction with changes in clinical state. Before treatment, depressed patients had a significantly lower Bmax (P less than 0.01) than age- and gender-matched healthy controls. After only 1 week of amineptine administration, Bmax values increased significantly (P less than 0.01) and reached the control value concomitantly with a large and significant clinical improvement (P less than 0.01). After 1 month, Bmax was still significantly different from the pretreatment value (P less than 0.05), and not significantly different from the control value, while the improvement in clinical status persisted. No significant changes in Kd values were observed during treatment. We also verified that amineptine did not displace 3H-imipramine binding from platelets either in depressed or in control subjects. The results show that the successful treatment with amineptine, an antidepressant drug devoid of affinity for the tritiated imipramine platelet binding site, can rapidly lead to its density normalization. PMID- 1607148 TI - What is congenital hepatic fibrosis? AB - The hypothesis presented in this paper suggests that, at birth, the basic lesion of congenital hepatic fibrosis corresponds to ductal plate malformation of interlobular bile ducts, resulting from faulty development, i.e. disturbance in epithelio-mesenchymal inductive interactions. The immature bile ducts are subject to a progressive destructive cholangiopathy, resulting in a pattern of more or less advanced fetal type of biliary fibrosis. The destructive cholangiopathy may be of variable speed and duration in different patients. The renal lesions in autosomal recessive polycystic kidney disease, which is most often associated with congenital hepatic fibrosis, show a comparable pattern and evolution. The hypothesis that congenital hepatic fibrosis corresponds to a fetal type of biliary fibrosis would explain a number of disparate observations. According to this concept, congenital hepatic fibrosis does not correspond to a single clinical entity but to a broad, merging spectrum of conditions. All have in common that they represent some stage of biliary fibrosis, usually of the fetal type, rarely of the adult type, resulting from a slowly progressive, destructive cholangiopathy. PMID- 1607149 TI - Pathological prognostic factors in breast cancer. II. Histological type. Relationship with survival in a large study with long-term follow-up. AB - The histological tumour type determined by current criteria has been investigated in a consecutive series of 1621 women with primary operable breast carcinoma, presenting between 1973 and 1987. All women underwent definitive surgery with node biopsy and none received adjuvant systemic therapy. Special types, tubular, invasive cribriform and mucinous, with a very favourable prognosis can be identified. A common type of tumour recognized by our group and designated tubular mixed carcinoma is shown to be prognostically distinct from carcinomas of no special type; it has a characteristic histological appearance and is the third most common type in this series. Analysis of subtypes of lobular carcinoma confirms differing prognoses. The classical, tubulo-lobular and lobular mixed types are associated with a better prognosis than carcinomas of no special type; this is not so for the solid variant. Tubulo-lobular carcinoma in particular has an extremely good prognosis similar to tumours included in the 'special type' category above. Neither medullary carcinoma nor atypical medullary carcinoma are found to carry a survival advantage over carcinomas of no special type. The results confirm that histological typing of human breast carcinoma can provide useful prognostic information. PMID- 1607150 TI - Characterization of the inflammatory infiltrate in ovarian dysgerminoma: an immunocytochemical study. AB - The inflammatory infiltrate has been characterized in 10 cases of ovarian dysgerminoma using a panel of antisera to T-cells, B-cells and macrophages. The expression of Class II major histocompatibility complex (MHC) antigens and the distribution of interferons alpha and gamma were also examined. T-lymphocytes were present in all tumours, often closely admixed with neoplastic elements. T cells in most areas were immunoreactive with gamma interferon. B-cells were generally scanty although germinal centres were present in three tumours. Immunocytochemistry revealed greater numbers of macrophages than had been appreciated on routinely stained sections. Macrophages were closely related to both lymphoid and tumour cells, and many macrophages were immunoreactive for alpha interferon. Class II MHC expression was mainly restricted to macrophages and B-cell areas although occasional T-cells were also stained. Dysgerminoma cells did not express Class II MHC antigens. PMID- 1607151 TI - Nasopharyngeal and nasal malignant lymphoma: a clinicopathological study of 54 cases. AB - Forty-one cases of nasopharyngeal and 13 cases of nasal malignant lymphoma have been examined histologically and immunohistochemically. All of the cases were non Hodgkin's lymphoma; one case was of follicular type and the remaining 53 were of diffuse type. Large cell lymphoma comprised 48% of cases and most of the immunoblastic lymphomas showing pleomorphism occurred in the nose. Twenty-seven cases were of T-cell and 21 of B-cell phenotype. The predominance of T-cell lymphoma was due to an increased incidence of these in the nose, the T:B ratio of 3.33:1 contrasting with a 1:1.05 ratio in the nasopharynx. Nasopharyngeal lymphomas seem to show an intermediate incidence between the T-cell predominance in the nose and a B-cell predominance in the oropharynx. Since the large cell type of lymphoma was predominant, the differential diagnosis from undifferentiated carcinoma is important and is facilitated by the use of immunostaining methods. PMID- 1607152 TI - Symptomatic cysts in otherwise normal lungs of children and adults. AB - The clinical and pathological features of 28 lung cysts resected in the period 1980-1989, excluding those from patients with emphysema elsewhere in their lungs, have been reviewed. In 12 children aged 8 days to 17 years, five cysts were congenital adenomatoid malformations, three were bronchogenic cysts, two were intralobar sequestrations, one was a cystic haemangioma and one resembled the cysts excised from 16 adult patients. This latter group ranged in age from 20 to 62 years and included 11 cigarette smokers and five asthmatics. Twelve of these cysts were intralobar and four were attached by a pedicle to the pleural surface of the lung. All these cysts had a fibromuscular wall showing varying degrees of acute and chronic inflammation. The presence of at least a partial lining of epithelial cells in all the cysts was confirmed using an immunocytochemical marker. The surrounding lung did not show any significant pathology. These cysts are labelled as simple fibromuscular pulmonary cysts. In the childhood cases, a congenital cause could be established in the majority. The pathogenesis of the adult cysts remains unclear. The presence of inflammation in the cyst walls does not necessarily suggest a role for infection, as secondary infection of cysts cannot be ruled out. An aetiological role for local damage due to cigarette smoking or asthma must be taken into consideration. PMID- 1607153 TI - Intranasal malignant melanoma arising in an inverted papilloma. AB - A case of intranasal malignant melanoma arising in the epithelium of an inverted papilloma is described. The use of immunohistochemistry to delineate the in situ component of the malignant tumour is illustrated and the characteristic features of malignant melanomas at this site discussed. PMID- 1607154 TI - Myxoid change within cellular blue naevi: a diagnostic pitfall. AB - We describe four cases of a distinctive myxoid change located in the centre of cellular blue naevi. Because all the reported lesions were large and were present on pressure-exposed locations, the myxoid change is thought to be caused by pressure together with direct repeated minor tissue trauma. PMID- 1607155 TI - Leiomyosarcoma of the nipple. PMID- 1607156 TI - Malignant thyroid haemangioendothelioma in a non-endemic goitrous region, with immunohistochemical evidence of a vascular origin. AB - A case of malignant haemangioendothelioma of the thyroid is presented in a patient resident in a non-endemic goitrous region of England. The tumour's endothelial origin was confirmed by factor VIII-related antigen and Ulex europaeus lectin staining. PMID- 1607157 TI - Inflammatory fibroid polyp of the terminal ileum presenting in a patient with active Crohn's disease. PMID- 1607159 TI - Polymorphous low-grade adenocarcinoma. PMID- 1607158 TI - Hepatic fibrin-ring granulomas. PMID- 1607160 TI - Folliculotropic Rosai-Dorfman disease. PMID- 1607161 TI - Hospitals strive to provide communities with benefits. AB - The time is now for community benefit standards programs. Indeed, not-for-profit hospitals are picking up the pace in this area and adopting such programs, motivated by a wide range of factors external and internal. On the one hand, increased public scrutiny of the not-for-profit institution's role, increased attention from the IRS, and encouragement at the national hospital association level are all influences here. But there is also a growing feeling among many hospitals that community benefit standards programs can enhance their public image--and that they're the right thing to do. PMID- 1607162 TI - TQM shifts hospital-vendor focus to total value, productivity. AB - The movement toward total quality management (TQM) is not only overturning the old ways of doing things within hospitals, it's transforming working relationships with vendors as well. A number of institutions are trying innovative approaches to purchasing, including vendor certification programs. PMID- 1607163 TI - HCFA's Medicare mortality data: the controversy continues. PMID- 1607164 TI - 1992 bond defaults provide key lessons for other hospitals. PMID- 1607165 TI - Inventors of DRGs look at PPS now. Interview by Marybeth Burke. AB - The inventors of diagnosis-related groups talk about what's happened to their invention, both in the U.S. and abroad. DRGs were used as the basis for Medicare's prospective payment system, but John D. Thompson and Robert B. Fetter, winners of the 1992 Baxter Foundation Prize for Health Services Research, say things haven't turned out exactly as they'd expected. PMID- 1607166 TI - Hospitals move cooperatively toward automation. AB - Hospitals are finding new ways to get their employees to "buy in" to new computer systems. An added bonus: With acceptance comes team building. PMID- 1607167 TI - Providers develop specialized AIDS home care programs. PMID- 1607168 TI - Recent Virginia case challenges COBRA applicability. PMID- 1607169 TI - AAFP (American Academy of Family Physicians): reform hinges on more family MDs. PMID- 1607170 TI - Openness is the key to trustee bonding. AB - Openness is vital for developing strong relationships between senior management and trustees, CEOs say. They cite one-on-one interaction and board retreats as effective tools for bonding. PMID- 1607171 TI - Reform advocate. The AHA's Davidson takes a candid look at health care reform. Interview by Mary Grayson. PMID- 1607172 TI - Beyond four walls. CEOs break new ground as community leaders. PMID- 1607173 TI - Voices of the people. Health care reform topic is timely, but hard to explain. PMID- 1607174 TI - Educating the public. Hospitals help spell out the basics of reform plans. PMID- 1607175 TI - A return to the town meeting. Rural hospitals reach out to their communities in planning services. PMID- 1607177 TI - Patients at the center. CEO discusses national project to refocus patient care delivery. Interview by Paula Eubanks. PMID- 1607176 TI - From RBRVS to job stress. Medical specialty leaders discuss key issues facing their members. Interview by Mary T. Koska. PMID- 1607178 TI - Narrowing the options. Employers turn to direct contracts, purchasing alliances. PMID- 1607179 TI - Data watch. First quarter 1992 data from AHA Monitrend II. PMID- 1607180 TI - When two worlds collide. PMID- 1607181 TI - How the door opened: the peopling of the New World. AB - The timing, pathways, and number of migrations involved in the early peopling of the New World are examined from a variety of perspectives. Ultimately, the occupation of the Western Hemisphere was a direct result of boreal cultural adaptations in the Old World. Here, we discuss (1) the dates of appearance of these boreal cultural adaptations and their relevance to the peopling of America, (2) archeological and linguistic evidence bearing on the earliest peopling of the New World, (3) ecological and linguistic evidence on two alternative routes into the New World, and (4) the assumptions present in various migration models. The relative strengths of opposing hypotheses are analyzed by observing whether different approaches point to the same answers. PMID- 1607182 TI - Peopling of the Americas: paleobiological evidence. AB - A subjective and bivariate analysis of 8500-10,000-year-old human fossil remains from North America substantiates that the fossils' closest affinities are with Asian populations. Within North American prehistoric Indian populations, increasing brachycephalization and the possible development of a larger, broader face are two structural trends that can be identified. In those respects where Paleo-Indian specimens differ from modern northern Asians and North American Indians, they tend to resemble southern Asian and European populations. These assessments generally support the inference that populations entered the New World relatively recently but before the modern northern Asian and North American features were fully developed. Based on the data examined, no date can be specified for time of entrance of the first populations, nor can the number of founding populations be discerned. PMID- 1607183 TI - New approaches to the study of disease in archeological New World populations. AB - One of the objectives of paleopathology is to clarify the role of disease in the evolution of human groups. The recovery of DNA and immunoglobulins from archeological human skeletal tissue offers a method for enhancing and expanding our knowledge about the presence and significance of disease in past human populations. DNA also might reveal the presence of genetic disease. Immunoglobulins recovered from archeological bone indicate some of the diseases to which an individual was exposed during life. This information also provides supporting evidence for anatomical observations of skeletal disease. This is illustrated by the identification of treponemal antibody in an archeological skeleton that has gross lesions suggestive of treponematosis. Similar biochemical methods could be applied to other research problems to clarify the presence of various syndromes of the inflammatory erosive arthropathies, such as rheumatoid arthritis, in New World archeological populations. Some of these syndromes are associated with DNA sequences and specific proteins that are recoverable from archeological skeletal tissue. PMID- 1607184 TI - Patterns of demographic change in the Americas. AB - Considerable scholarly debate has focused on the nature of demographic change in the Americas before and after 1492. Recent research on human skeletal samples and related archeological materials suggests that morbidity and mortality were increasing throughout much of the Western Hemisphere before 1492 in response to increased population density, increased sedentism, and changing subsistence. The evidence suggests that after 1492 population reduction was caused not by continental pandemics but by localized or regional epidemics augmented by social and economic disruption. The twentieth century has witnessed remarkable Native American population recovery, fueled both by improvements in health care and changing definitions of "being Indian." PMID- 1607185 TI - Immunoglobulin allotypes (GM and KM) indicate multiple founding populations of Native Americans: evidence of at least four migrations to the New World. AB - On the basis of GM and KM typing and language, approximately 28,000 Amerindians were divided into 4 groups of populations: non-Nadene South American (8 groups), non-Nadene North American (7 groups), Nadene (4 groups), and Eskaleuts (6 groups). These groups were compared to four groups of Asian populations. The distribution of GM haplotypes differed significantly among and within these groups as measured by chi-square analysis. Furthermore, as reflected in a maximum linkage cluster analysis, Amerindian populations in general cluster along geographic divisions, with Eskaleuts and Nadenes clustering with the Asian populations and non-Nadene North American and non-Nadene South American populations forming two additional clusters. Based on GM haplotype data and other genetic polymorphisms, the divisions appear to reflect populations that entered the New World at different times. It appears that the South American non-Nadene populations are the oldest, characterized by the haplotypes GM*A G and GM*X G, whereas later North American non-Nadene populations are characterized by high frequencies of GM*A G and low frequencies of GM*X G and GM*A T. In contrast, Eskaleuts appear to have only GM*A G and GM*A T. The Nadene speakers have GM*X G and GM*A T in higher and approximately equal frequencies. Maximum linkage cluster analysis places the Alaskan Athapaskans closest to northwestern Siberian populations and the Eskaleuts closest to the Chukchi, their closest Asian neighbor. These analyses, when combined with other data, suggest that, in the peopling of the New World, at least four separate migrant groups crossed Beringia at various times. It appears likely that the South American non-Nadene entered the New World before 17,000 years B.P. and that the North American non-Nadene entered in the immediate postglacial period, with the Eskaleut and Nadene arriving at a later date. PMID- 1607186 TI - Patterns of genetic variation in Native America. AB - Allele frequencies from seven polymorphic red cell antigen loci (ABO, Rh, MN, S, P, Duffy, and Diego) were examined in 144 Native American populations. Mean genetic distances (Nei's D) and the fixation index FST are approximately equal for the North and South American samples but are reduced in the Central American geographic area. The relationship between genetic distance and geographic distance differs markedly across geographic areas. The correlation between geographic distance and genetic distance for the North and Central American data is twice as large as that observed for the South American samples. This geographic difference is confirmed in spatial autocorrelation analyses; no geographic structure is apparent in the South American data but geographic structure is prominent in North and Central American samples. These results confirm earlier observations regarding differences between North and South American gene frequency patterns. PMID- 1607187 TI - Variation among North Amerindians: analysis of Boas's anthropometric data. AB - In the late nineteenth century Franz Boas was responsible for assembling anthropometric data from North Amerindians. Approximately 15,000 subjects were measured, but the data have never been systematically analyzed. Here we describe our efforts to develop a computerized database from Boas's data and present the first systematic analysis of these data. In addition to a general analysis of North Amerindian anthropometric variation, we also present a more detailed analysis of anthropometric variation among tribes located in the American Northwest. In the general analysis we find that anthropometric variation is strongly patterned along geographic lines. We examine geographic and language patterning by grouping tribes by culture area and language phylum. Both have high explanatory power, culture area being the higher. The Northwest analysis shows that both language and geographic location are important in explaining anthropometric variation. PMID- 1607188 TI - Resuscitation in HIV. PMID- 1607189 TI - Intensive care for advanced HIV disease. PMID- 1607190 TI - Bullous impetigo in homosexual men--a risk marker for HIV-1 infection? AB - OBJECTIVE: To determine the incidence of bullous impetigo in a group of homosexual men at high risk of HIV-1 infection. DESIGN: A longitudinal descriptive study (1984-9). SETTING: A private primary care and STD clinic in Sydney, Australia. SUBJECTS: 88 homosexual men documented to seroconvert to HIV 1, and 37 homosexual controls who had practised unprotected anal intercourse with another man known to be HIV-1 positive but who remained HIV-1 negative. MAIN OUTCOME MEASURE: Incidence of bullous impetigo. RESULTS: The crude annual incidence of bullous impetigo was 0.015 in subjects while they remained HIV-1 negative (10 cases) and 0.045 in early HIV-1 positive subjects (2 cases). Overall, 9% of the HIV-1 seroconverters and 9% of the HIV-1 negative controls were documented as suffering bullous impetigo over a mean of 29.2 and 39.3 months, respectively. CONCLUSIONS: Bullous impetigo in an adult could prove to be a clinical indication that a person is either infected with HIV-1 or is in close (possibly sexual) contact with a person with HIV-1 infection. If true, the recognition of bullous impetigo could provide an opportunity for behavioural intervention to limit the spread of HIV-1. PMID- 1607191 TI - Lidocaine/prilocaine cream (EMLA(R)) versus infiltration anaesthesia: a comparison of the analgesic efficacy for punch biopsy and electrocoagulation of genital warts in men. AB - OBJECTIVES: To compare analgesic efficacy and pain caused by administration of lidocaine/prilocaine cream (EMLA(R)) versus xylocaine 1% local infiltration for punch biopsy and electrocoagulation of genital warts in men. DESIGN: Open randomised comparative parallel-group study. SETTING: Department of Dermatovenereology, University Hospital Rotterdam/Dijkzigt, the Netherlands. PATIENTS: 63 males with warts on the genital mucosa and/or perianal area. METHODS: EMLA(R) cream (2.5-5 g) was applied during 13-45 minutes before surgery. Xylocaine 1% (0.1-4 ml) was infiltrated 0.5-4 minutes before surgery. Pain during administration and surgery was assessed by the patient on a verbal rating scale and on a visual analogue scale. RESULTS: EMLA(R) application was painless in all patients (n = 31) whereas xylocaine infiltration was slightly painful in 17/29 patients and moderately painful in 10/29 patients. EMLA(R) analgesia was satisfactory for 94% of biopsies and 62% of electrocoagulations. Xylocaine infiltration was satisfactory in all procedures. CONCLUSIONS: EMLA(R) application on the male genital mucosa is painless but it has a lower analgesic efficacy than xylocaine infiltration. However EMLA is a useful anaesthetic for taking biopsies in this area and may be used as premedication for local infiltration. PMID- 1607192 TI - Penile dermatoses: a clinical and histopathological study. AB - OBJECTIVE: To assess the spectrum of genital dermatological conditions affecting men and compare the clinical and histopathological diagnoses. DESIGN: Prospective study over a one year period. SETTING: A central London teaching hospital. PATIENTS: Seventy one patients with unresponsive penile dermatoses attending a specific internal referral clinic within the department of genitourinary medicine and 36 patients undergoing penile biopsy following attendance at other departments within the same hospital. METHODS: Full dermatological assessment of patients attending the specific clinic. Standard histopathological methods were used in the diagnosis of biopsy specimens. OUTCOME MEASURED: Clinico-pathological diagnosis of cutaneous penile abnormalities. RESULTS: Description of the range and relative frequency of penile dermatological conditions. The most common histopathological diagnosis was of non specific dermatitis. Twenty seven percent (16 of 61) of patients attending the specific clinic and 33% (12 of 36) of men attending other departments had conditions requiring long term follow up. CONCLUSIONS: The ranges of penile dermatoses presenting to the different departments were broadly similar. Penile biopsy was shown to be a safe and clinically informative procedure. In the genitourinary clinic setting, clinical diagnosis prior to biopsy was found frequently to be inaccurate. PMID- 1607194 TI - The value of treating the sexual partners of women with recurrent vaginal candidiasis with ketoconazole. AB - OBJECTIVE: To determine whether treatment of the sexual partners of women with chronic vulvovaginal candidiasis with oral ketoconazole can reduce the recurrence rate of candida vaginitis. DESIGN: Single blind randomised study where all the women were treated with ketoconazole 400 mg daily for 7 days after an acute episode of candida vaginitis and half the male partners were treated with ketoconazole 200 mg daily for 5 days. SETTING: Women's Candida Clinic of St. Michael's Hospital, a University of Toronto teaching Hospital, Toronto, Ontario, Canada. SUBJECTS: Fifty-four women attending the clinic with at least four proven episodes of candida vaginitis and their male sex partners (stable monogamous relationships) were enrolled in the study. MAIN OUTCOME MEASURES: Clinical recurrence of candida vaginitis with confirmation by smear and culture. Follow-up was obtained one to two weeks after initial treatment, then monthly for one year. RESULTS: In the control group (untreated partners), 20 of 28 (71%) patients had recurrences in six months, versus 17 of 26 (65%) patients in the treated group (treated partners) (95% Confidence Interval (CI) for the difference in recurrence rate = -19% to 31%). At one year, 23 of 28 (82%) patients in the control group had recurrences, versus 22 of 26 (85%) in the treated group (CI = -23% to 17%). CONCLUSION: Treatment of the male partners, with a brief course of ketoconazole, is not of value in reducing the incidence of relapse in women with recurrent vaginal candidiasis. It is unlikely that a larger study would show a clinical important difference. PMID- 1607193 TI - Genomic fingerprinting of penicillinase-producing strains of Neisseria gonorrhoeae in Valencia, Spain. AB - OBJECTIVE: To compare the value of different markers and their combinations with the restriction enzyme technique in the differentiations of penicillinase producing N. gonorrhoeae (PPNG) strains. MATERIALS AND METHODS: 17 PPNG strains isolated from symptomatic, untreated male patients with urethritis were characterised by antibiotic sensitivity testing, auxotyping, serotyping, plasmid profile, and restriction endonuclease fingerprinting (Hind III digestion). Cluster analysis with the method of unweighted pair-group average (UPGMA) linkage was used to calculate similarity or dissimilarity for PPNG strains. MAIN RESULTS: Either auxotyping or plasmid profile alone differentiated three groups of PPNG strains, whereas the combination auxotyping/serotyping identified 10. Although the combination auxotyping/serotyping/plasmid profile and the restriction enzyme technique showed a similar discrimination ability (differentiation of 11 PPNG strains), genomic fingerprinting gave highly specific restriction patterns on individual gonococcal isolates. CONCLUSIONS: The combination of different markers gave more epidemiological information than the use of only one. The sequence of discriminating ability for PPNG strains was: auxotyping/serotyping less than auxotyping/serotyping/plasmid profile less than restriction patterns of genomic DNA. PMID- 1607195 TI - Lichen sclerosus and acute urinary obstruction. AB - A case of acute urinary obstruction due to early lichen sclerosus disease is described. In this case both histological corroboration and efficacy of potent topical steroid have been beneficial. PMID- 1607196 TI - Chronic microsporidian infection of the nasal mucosae, sinuses and conjunctivae in HIV disease. AB - A case of chronic infection of the nasal mucosae, sinuses and conjunctivae with a microsporidian parasite in association with HIV infection and immune deficiency is reported. This microsporidian resembles both Encephalitozoon cuniculi and the newly described Encephalitozoon hellem by electron microscopy. This occurred in an adult male resident in the UK with no history of foreign travel. Although there are previous descriptions of conjunctival infections from the USA, this is the first description of infection of the nasal epithelium. Further studies are underway to classify this protozoan. PMID- 1607197 TI - Sexually transmitted infections in selected high risk populations in Cameroon. PMID- 1607198 TI - Carriage of Chlamydia trachomatis by elderly people. PMID- 1607199 TI - Annular lesions in congenital syphilis. PMID- 1607200 TI - Antitrichomonal (cross) immunity as an important factor in vulvar vestibulitis syndrome pathogenesis. PMID- 1607201 TI - Large loop excision of the transformation zone (LLETZ) or loop diathermy. PMID- 1607202 TI - Sexually transmitted disease [STD] control. PMID- 1607203 TI - 1991 survey of cervical cytology in English genitourinary medicine clinics. PMID- 1607204 TI - Heterosexual transmission of HBV in Caucasians attending a genitourinary medicine clinic. PMID- 1607205 TI - HIV infection in Tirupati, India. PMID- 1607206 TI - Oral sex and recurrent vaginal candidiasis. PMID- 1607207 TI - Antibiotic prophylaxis for cold coagulation of the cervix. PMID- 1607208 TI - Safe sex and women. PMID- 1607209 TI - A human monoclonal antibody derived from axillary lymph nodes of a breast cancer patient reactive to a sulfated glycolipid. AB - A human monoclonal antibody, BMMK-33G, was established by a fusion of human B lymphoblastoid cells, HO-323, with lymphocytes of axillary lymph nodes obtained from a breast cancer patient. High-performance thin-layer chromatography (HPTLC) immunostaining and enzyme-linked immunosorbent assay (ELISA) revealed that BMMK 33G was interestingly directed to enough sulfatide (Galactosylceramid-I2 sulfate), which is one of the sulfate ester containing glycolipids. By immunohistochemical staining, BMMK-33G intensely reacted to breast cancer, pancreatic cancer and gastric cancer. It also reacted to many normal human tissues including mammary glands, but these stainings were weaker than those for cancer. This report describes BMMK-33G, a human monoclonal antibody against sulfatide which may be very useful for studying not only tumor immunology but also autoimmune diseases. PMID- 1607210 TI - Characterization of a human-human hybridoma antibody, C-OU1, directed against a colon tumor-associated antigen. AB - The human hybridoma cell line, B9165, was obtained after fusion of lymphocytes from lymph nodes draining the tumor region in a patient with adenocarcinoma of the colon with the human B-lymphoblastoid cell line WI-L2-729-HF2 (729-HF2). B9165 secretes the human monoclonal antibody, C-OU1 (IgM, kappa). Immunocytochemical and immunohistochemical analysis showed that the antibody bound to a differentiation antigen. Electron microscopy of colonic adenocarcinoma cells, intact tumor and colonic epithelium by the immunogold technique demonstrated that the C-OU1 antibody reacted with a molecule associated with areas of disruption of the intermediate filaments in the cytoplasm of the tumor cells. No reaction was seen with intermediate filaments in normal colonic epithelium. The molecular weight of the antigen was shown to be 43 Kda by SDS PAGE and Western blotting of tumor extracts, and isoelectric focusing of sonicated extracts demonstrated reaction with molecular species of pI 5.4-6.2. These findings suggest that the C-OU1 antigen is a modified cytokeratin 18. The B9165 cell line has proved to be quite stable, and the antibody is of potential clinical value. Its usefulness for localizing tumors in patients is being investigated. PMID- 1607211 TI - Monoclonal antibody AP-282 recognizes a marker for human polymorphonuclear granules. AB - Hybridoma AP-282 was produced by fusing mouse plasmacytoma cells with splenocytes of mice immunized against purified human polymorphonuclear cells. The secreted monoclonal antibody (MAb), AP-282, a mouse IgG1, was found to react strongly with all neutrophilic granulocytes, their bone marrow precursors, weakly with blood monocytes and not with eosinophils. The antigen was resistant to formalin fixation but was destroyed by exposure to fixatives containing acetic acid. Using the APAAP technique, antibody AP-282 strongly labelled neutrophils on sections of frozen cut or paraffin embedded tissues. No staining was seen of non hematopoietic tissues. AP-282 recognized an internal antigen associated to cytoplasmic granules. Chemical investigations on dot blots of whole or of purified cellular extracts indicated that the antigen idenfied by MAb AP-282 was different from those recognized by usual antigranulocyte antibodies, i.e. myeloperoxidase, elastase, cathepsin G and lactoferrin. Thus, antibody AP-282 constitutes a new cytoplasmic marker of neutrophils. PMID- 1607212 TI - Monoclonal antibodies to human endothelin-1: characterization and utilization in radioimmunoassay and immunocytochemistry. AB - A host of monoclonal antibodies directed against human endothelin-1 (ET-1) has been developed and characterized. The antibodies reacted with ET-1 specifically and with high affinity, as determined by competition analysis and sucrose density gradients. The antibodies did not cross-react with neuropeptide YY, beta endorphin, calcitonin gene-related peptide, secretin or somatostatin. The antibodies cross-reacted with big endothelin (B-ET), endothelin-2 (ET-2), vasointestinal constrictor peptide (VIC), and endothelin-3 (ET-3) albeit with varying affinity but did not cross-react with sarafotoxin (SRTX-6b). None of the antibodies reacted with the C-terminal hexapeptide (HXPT) of ET-1, indicating that the epitopes are not located within this region of ET-1. The monoclonal antibodies exhibited binding activity in dilutions ranging from 1:1000, to 1:10(6). The isotypes of the monoclonal antibodies were determined by competition binding assay. Six of the monoclonal antibodies were of the IgG gamma 1, two were IgM and one of the IgG gamma 2a subclass. The antibodies detected immunoreactive ETs by radioimmunoassay and in immunocytochemical localization, suggesting the potential use of these antibodies as tools to determine the concentration of ETs in biological fluids and in immunocytochemical localization of ETs in specific cell types in various tissues. PMID- 1607213 TI - Chicken anti-protein A for the detection and capturing of protein A from Staphylococcus aureus in the presence or absence of mammalian IgG. AB - A sandwich-ELISA for the detection of protein A from Staphylococcus aureus (SpA) is described, using chicken anti-protein A as a capture antibody and its alkaline phosphatase conjugate for the detection of bound protein A. Traditionally, protein A is detected by its binding to the Fc part of a detector antibody. This binding will be influenced by the presence of other IgG in the protein A solution. However, SpA does not react with the Fc part of chicken IgG, and it is thus possible to detect protein A in IgG containing solutions, such as eluates from protein A-columns. The method can be used to detect 1 x 10(-7) g protein A/l in the presence of serum. The method is more sensitive if no serum or IgG is present in the solution. PMID- 1607214 TI - Spontaneous hybridoma formation induced by immunization with Haemophilus paragallinarum: evidence for a lipopolysaccharide fusion inducer. AB - The phenomenon of spontaneous fusion between myeloma cells and splenocytes from mice immunized with formalin-inactivated Haemophilus paragallinarum cells, has been reported on recently (1). The identity and properties of the bacterial inducer of fusogenicity of splenocytes have been further investigated with the aid of a monoclonal antibody VF3 against H. paragallinarum (2), which has a bacterial strain specificity correlating with the ability of the strains to induce spontaneous fusion between splenocytes of immunized mice and myeloma cells. It was shown that the lipopolysaccharide fraction of the bacteria was required for the induction of fusogenicity. LPS involvement was clearly indicated by the parallel effects on VF3 antigenicity and fusogenic inductivity of various treatments such as proteolytic digestion, periodate oxidation and sensitivity towards alkali, acid or freezing. PMID- 1607215 TI - Spousal characteristics as predictors of well-being in older couples. AB - This study examined the relations between spousal variables and the psychological well-being of husbands and wives in older couples to determine if spousal characteristics were more important determinants of well-being for wives than for husbands. One hundred-twenty older married men and women completed standardized self-report measures and a short interview. The variables investigated included education, verbal intelligence, personality, physical health, marital adjustment, psychological well-being, as well as response bias to marital defensiveness. Spousal variables significantly predicted wives' well-being (R2 = 29%) with the three most influential predictor variables being the husbands' perception of the marriage, positive dimension of well-being and physical health. In contrast, spousal variables did not significantly predict husbands' well-being. The study supported the hypothesis of differential responsiveness of men and women to spousal variables and highlighted the importance of marital adjustment for the psychological well-being of older wives. PMID- 1607216 TI - Intergenerational talk and communication with older people. AB - A program of research conducted within an anti-agism paradigm demonstrates that young people process and respond to the speech of older people in stereotypical ways. Such conclusions result from studies using a variety of research methods. Experimental studies demonstrate that older-sounding speech triggers age schematic responses and that young people tend to use agist strategies of information seeking and compliance gaining from older people, while interactive studies explore how stereotypes and age identities are co-produced by young and old people in conversation. We use lifespan and intercultural perspectives to argue that the communicative patterns we observe in our studies are in some senses and contexts counterproductive in both the long and short term, in that they can reproduce negative attitudes toward aging as well as inhibit successful aging. PMID- 1607217 TI - A flaw in gerontological assessment: the weak relationship of elderly superficial life satisfaction to deep psychological well-being. AB - This study assessed the degree of relationship between superficial and deep psychological adjustment among elderly individuals. Eighty-six middle-class, Anglo persons averaging seventy-six years of age participated. Roughly one-half of the sample were "independent living," with the other half "congregate apartment dwelling." A similarly equal representation of both sexes was achieved. Superficial psychological well-being was measured using Cantril's Self-Anchoring Scale for life satisfaction, while deep psychological well-being was measured using portions of the Eriksonian-based Measures of Psychosocial Development. It was hypothesized that no more than a moderate correlation (.50) would be found to exist between shallow and deep psychological adjustment. This hypothesis was confirmed, suggesting that gerontologists need to cease relying on superficial psychological measures for elderly assessment, and implement more depth-oriented tests. It is argued that failure to do this promulgates an unfortunate tradition of shallow, inaccurate psychological measurement within gerontology. PMID- 1607218 TI - Dimensions of self-report about everyday memory in young and older adults. AB - This study investigated the relationship between several aspects of memory self report, objective memory, attitude toward intellectual aging, self-rated health, and self-rated depression in young and older adults. Participants completed a self-report depression scale, and then rated their discomfort with eight categories of everyday forgetting and their attitudes toward intellectual aging. One week later, they rated how frequently they experience the same categories of forgetting, and then completed a battery of objective memory tests analogous to those categories. Ten days later, they rated their willingness to participate in both memory improvement classes and nonmemory classes. Older adults reported significantly more frequent failures but less discomfort with the failures than the young adults. Frequency, discomfort, and self-reported depression were all positively correlated in the older group, but not the young group. Young and old adults were equally positive about participating in memory classes, which both age groups preferred to nonmemory classes; the correlation between willingness to participate in memory classes and objective memory approached significance in the young, but not in the old. Attitude toward intellectual aging was correlated with frequency of and discomfort with forgetting in the older group. PMID- 1607219 TI - The definitions of the beginning of old age in history. AB - The beginning of old age has been addressed by many writers and scholars over the centuries. From ancient literature to contemporary times, most authorities have located the beginning of old age around age sixty, although some thought it started around age forty. High mortality rates had negligible effects on when old age was thought to begin. Gender may have had more influence, as women were consistently viewed as aging more rapidly and sooner than men. Overall, the age range thought to start old age has been fairly consistent. Nevertheless, within historical contexts varying opinions on the beginning of old age have co-existed, and distinctions between young-old and old-old have been acknowledged. Initially, external factors were viewed as affecting the beginning of old age, but as history unfolded, more emphasis was placed on the individual's relationship with society and ability to perform tasks. With the rise of formal retirement, less emphasis was placed on the individual's ability and more on chronological age. Thus, defining the beginning of old age returned to external factors, such as governmental and economic definitions, and became based on chronological age. In the future, these factors may either lead to new parameters or perhaps a questioning of whether it is even necessary to define the beginning of old age. PMID- 1607220 TI - Expectations and outcomes after hip fracture among the elderly. AB - Hip fractures among the elderly are a common occurrence, with high social and personal costs. Sequelae not infrequently include loss of independent functioning, permanent disability, and death. This prospective study of a cohort of eighty recently diagnosed "hardy" hip fracture patients examines initial rehabilitation expectations using a combination of methods. The study addresses the relationship between initial expectations and changes in ambulatory status from prefracture to three months post-fracture. The importance of previous experience with illness is also explored. Participants who had positive expectations for recovery and those who had greater previous experience were likely to have less negative change in ambulation from prefracture to three months, and better overall ambulation at three months. The findings suggest a relationship between patient expectations for recovery and actual recovery of ambulation, and support the heretofore "clinical impression" that cognition and affect influence the course of rehabilitation after hip fracture. PMID- 1607221 TI - Autoradiographic studies of aged primate macular retinal pigment epithelium. AB - The authors used 35S-sulfate and 3H-proline to trace labeled molecules in autoradiograms of aged monkey and human macular retina to detect the synthesis of extracellular matrix (ECM) components by retinal pigment epithelial (RPE) cells. Quantitative analysis of silver grains 6 hr and 3 d after intravitreal injection of 35S-sulfate in the monkey showed that secretion from the basal pole of the RPE occurs at a slower rate than from the apical pole. In vitro incubation of human maculas produced poor autoradiographs with 35S-sulfate. Good autoradiographs were obtained using 3H-proline. Human macular RPE showed uneven labeling, but densely labeled cells did not correlate with sites of basal linear deposits, ECM though to be basement membrane material, and a hallmark of age-related maculopathy. The time course of labeling in adult primate tissue showed a fairly high turnover rate for these molecules. Scant labeling of ECM at drusen sites and no labeling in basal linear deposits suggested that either (1) these structures have a slow turnover or (2) their components contain scant sulfate and proline. Alternatively, faulty degradative processes rather than enhanced synthesis may account for the accumulation of abnormal ECM at the RPE-Bruch's membrane interface in aged maculas. PMID- 1607222 TI - Lipid peroxidation in rod outer segments. Role of hydroxyl radical and lipid hydroperoxides. AB - Lipid peroxidation of rod outer segment (ROS) membranes has been implicated in the pathogenesis of numerous ocular disease processes. The hydroxyl radical might be involved in initiating the reaction. An in vitro system was developed to study lipid peroxidation of the ROS and the role of the hydroxyl radical. Bovine ROS were suspended in various concentrations of ferrous sulfate, incubated for 10 min at 37 degrees C, treated with diethylenetriamine pentaacetic acid to chelate the iron, and subjected to a thiobarbituric acid assay for malondialdehyde. A predictable increase in lipid peroxidation occurred in the presence of Fe+2. No effect was seen in the presence of Fe+3. Adding hydrogen peroxide, which would form the hydroxyl radical by reacting with Fe+2, had no effect at low concentrations. At higher concentrations, lipid peroxidation was inhibited, presumably from the oxidation of Fe+2 to Fe+3. Ethanol, a known hydroxyl radical scavenger, had no inhibitory effect in concentrations up to 0.50 mol/l. Conversely, cumene hydroperoxide and linoleic acid hydroperoxide, which form hydrophobic radicals, stimulated lipid peroxidation in the presence of Fe+2. These findings suggest that, under these experimental conditions, the hydroxyl radical is not an initiator of lipid peroxidation in ROS. They provide evidence that endogenous lipid radicals may initiate the reaction. PMID- 1607223 TI - Encapsulation of sodium fluorescein for dye release studies. AB - Recent investigations have detailed a selective dye release technique in which a pulse of laser light induces the release of a fluorescent dye from temperature sensitive liposomes circulating in the retinal vasculature. This dye release technique has made possible a new method for measuring ocular blood flow in the retina and has spurred the development of repetitive, site-specific angiography. However, sodium fluorescein, the dye employed clinically for angiography of the retina, has not been employed in the aforementioned studies because of its rapid efflux from liposomes. This report outlines a method for stable encapsulation of sodium fluorescein in temperature-sensitive liposomes. Heat-induced leakage of the dye from liposomes in vitro was similar to that previously seen with other fluorescent dyes. Furthermore, after intravenous injection of encapsulated fluorescein in a nonhuman primate, dye released by a pulse of laser light allowed excellent visualization of the retinal architecture. These results indicate that sodium fluorescein, a dye that has proven to be the agent of choice for sensitive detection of leakage of vessels of the retina, can be released at a specific site in the retinal vasculature. Direct comparisons of the diagnostic capability of free and encapsulated sodium fluorescein are now possible. PMID- 1607224 TI - Vascular changes and their mechanisms in the feline model of retinopathy of prematurity. AB - This study documents changes to retinal vasculature during the feline form of retinopathy of prematurity (ROP). The authors describe the closure and obliteration of retinal vessels during exposure to high oxygen, the pattern and tempo of growth of proliferative vasculature, which, after the return of the animal to room air, extends from the optic disc in a spectacular "rosette" pattern, the formation of preretinal vascular growths, and an initial lack of barrier properties in the new vessels. Finally, the response of the vasculature to the relief of hypoxia is reported, including the gradual establishment of barrier properties in the intraretinal vessels, the partial normalization of the proliferative vessels, and the abnormalities that persist. It is suggested that the vascular changes occur in successive stages: closure and obliteration during hyperoxia, vasoproliferation induced by hypoxia, and normalization after the relief of hypoxia with distinct cellular mechanisms and stimuli. It is argued that the same stages can be seen in the human form of ROP; two possible stimuli for the fibroplasia that damages the retina in human ROP are discussed. PMID- 1607225 TI - Degeneration of astrocytes in feline retinopathy of prematurity causes failure of the blood-retinal barrier. AB - This study addresses the role of astrocytes in the genesis of retinopathy of prematurity, examined in the feline model of this condition. Evidence is presented that the hypoxia of retinopathy of prematurity, in addition to inducing vasoproliferation, damages the retina directly. Retinal neurons survive the hypoxia, but the astrocytes, which are involved in the formation of the glia limitans of the retinal vessels, degenerate. Astrocytes subsequently recolonize the retina after a delay that matches the period of leakiness of the proliferative vasculature (described in the companion article). Given the evidence from other studies that the barrier properties of vessels are induced by their glia limitans, the authors suggest that the initial lack of barrier properties in the new vasculature is caused by the degeneration of astrocytes and that the subsequent formation of those properties is induced by the astrocytes that recolonize the retina some days later. The observation that astrocytes are more sensitive to hypoxia than neurons, at least in developing tissue, was unexpected. The literature reporting on the damage caused to central nervous tissue by hypoxia is consistent in assessing neurons as more sensitive and glial changes as a reaction to neuronal damage. The sensitivity of astrocytes found in this study and earlier in vitro research suggests that degenerated astrocytes can be replaced and their structural and functional relationships reestablished. PMID- 1607226 TI - The effect of combined daunorubicin and triamcinolone acetonide treatment on a refined experimental model of proliferative vitreoretinopathy. AB - Prior studies have shown that intravitreal daunorubicin (9-15 nmol) and triamcinolone acetonide (2 mg) are effective individually in preventing retinal detachment in experimental proliferative vitreoretinopathy. This report compares the efficacy of the combination of daunorubicin (15 nmol) and triamcinolone acetonide (2 mg) with that of daunorubicin alone in a refined experimental model of proliferative vitreoretinopathy. The degree of retinal detachment in each treatment group was graded, with the unequivocal absence or presence of retinal detachment used as an indicator of treatment success or failure. Both treatments (daunorubicin alone and in combination with triamcinolone acetonide) effectively prevented retinal detachment. However, there was no significant difference in the rate of retinal detachment between the two treatment groups. These results indicate that combination therapy with daunorubicin/triamcinolone is no more effective at preventing retinal detachment than daunorubicin alone. PMID- 1607227 TI - Effect of a metalloproteinase inhibitor on established corneal ulcers after an alkali burn. AB - Proteinase inhibitors have been shown to prevent corneal ulceration and perforation when used immediately after an experimental alkali burn injury. To evaluate the clinical efficacy of a synthetic metalloproteinase inhibitor, HSCH2CH[CH2CH(CH3)2]CO-Phe-Ala-NH2(SIMP), treatment with inhibitor was withheld until corneal ulceration ensued after a standard alkali injury to the rabbit eye. When topical therapy with a 1 mmol/l solution of SIMP was initiated after corneal ulceration had progressed to a mid-stromal level (clinical score of 2), there was no significant difference in the progression of corneal ulceration between the treated vs. control group after 6 d of therapy. In the second study in which treatment was initiated earlier at the onset of superficial ulceration (clinical score of 1), there was a significant difference in clinical scores between the two groups after 1 day of treatment until termination of the experiment at 21 d (P less than 0.005). In the inhibitor-treated group, 88.9% of the corneas showed a reversal or cessation of progression of the ulceration process. Eighty-seven and-a-half percent of the control corneas progressed to descemetocele formation or perforation by day 14 of treatment. This study suggests that SIMP may be used for effective treatment of corneal ulcers resulting from an alkali burn injury in the human eye. It also shows that early and aggressive initiation of therapy is critical. PMID- 1607228 TI - Gas chromatographic and mass spectroscopic analysis of excimer and erbium: yttrium aluminum garnet laser-ablated human cornea. AB - The photoablative products from human cadaver corneas treated with lasers were investigated using gas chromatography and mass spectroscopy. The photoablations were done separately with an excimer laser (193 nm) and with an erbium: yttrium aluminum garnet (Er:YAG) laser (2.94 microns). More than 20 different types of molecules with a molecular weight of 40-400 mass units could be identified, most of which were found to be alkanes. The comparison of the two types of laser ablations showed larger fragments and fewer types of molecules present after excimer laser treatment than after Er:YAG photoablation. PMID- 1607229 TI - Noncross-linked collagen discs and cross-linked collagen shields in the delivery of gentamicin to rabbits eyes. AB - Using fluorescent polarization immunoassay, in vitro absorption and elution of gentamicin by noncross-linked collagen discs was measured. This technique was compared with that of cross-linked collagen shields and topical drops to provide adequate gentamicin levels in the cornea and aqueous humor of the rabbit eye. In vitro results showed that the noncross-linked collagen discs absorbed increased gentamicin with prolonged soaking time. All 2-hr presoaked discs completely dissolved within 6 min after being placed in the lower fornix of the rabbit eye. The presoaked discs released most of their gentamicin load within 0.5 hr of elution. Gentamicin levels in the cornea and aqueous humor, using 2-hr presoaked discs, were similar to those obtained with a single drop (P greater than 0.05) of topical solution and significantly lower than those obtained by applying a collagen shield at all intervals (P less than 0.01) and by hourly drops measured at 4- and 6-hr intervals (P less than 0.01). These results suggest that, in their current formulation, the presoaked collagen discs may not be an effective alternative to collagen shields or topical drops for gentamicin delivery because of their rapid dissolution in the eye. PMID- 1607230 TI - Localization of corneal epithelial stem cells in the developing rat. AB - A monoclonal antibody, 4G10.3, was developed that preferentially binds limbal basal cells in adult rat, rabbit, and human corneas. These cells were hypothesized to be the stem cells for the corneal epithelium. The antibody 4G10.3 was localized by immunofluorescence microscopy in rats 1 d and 1, 1.5, 2, 3, 4, and 6 wk of age. Until 1.5 wk, 4G10.3 bound intensely to all basal cells in the cornea and the limbus. At 2 wks, the basal cells at the central cornea abruptly changed their shape from flattened or ovoid to large and cuboidal and bound 4G10.3 with greatly reduced intensity. Increased stratification of epithelium also was seen. Cells binding 4G10.3 gradually became sequestered to the limbal area after 2 wk, concomitant with increased stratification. At 4 and 6 wk, 4G10.3 binding was identical to that in adult corneas with only limbal basal cells showing positive binding. Basal cells in the limbal epithelium did not decrease their intense binding of 4G10.3 or change their ovoid cellular shape from 1 d through adult life. These results suggest that, during development, stem or stem like cells are localized throughout the basal layer of the corneal and limbal epithelium. As the cornea matures, these cells are sequestered in the limbus at the same time that stratification of the epithelium and shape changes occur in the basal cells. PMID- 1607231 TI - The effect of systemic decomplementation with cobra venom factor on corneal complement levels in guinea pigs. AB - The authors examined the effect of systemic administration of cobra venom factor (CVF) on hemolytic complement levels in guinea pig sera and corneas. Guinea pigs received repeated intraperitoneal injections of CVF. Sera and corneas were obtained before and 1, 2, 5, 8, 10, 12, 16, and 20 d after the initial injection of CVF. Total hemolytic complement activity was measured by lysis of sheep erythrocytes sensitized with rabbit antibodies. There was a significant decrease in serum complement levels at days 1, 2, 5, 8, and 10 after the initial injection of CVF. After this, complement levels rose to levels that exceeded preinjection values. Complement levels in corneas also declined after CVF injections with a significant decrease at days 2, 5, 8, and 10 and a return to normal thereafter. Corneal complement depletion and restoration lagged behind serum. Moreover, the rate of complement depletion and restoration was greater for serum than cornea. Light microscopic examination of representative corneas at each time did not show local tissue changes during decomplementation. This is first study (to the authors' knowledge) to document corneal complement depletion by systemic administration of CVF. Low-to-absent corneal complement levels were present 2 d after the initial injection of CVF and persisted for 6 d. This model could be used to study the influence of complement on traumatic and immunologic injuries to the cornea. PMID- 1607232 TI - Intraocular pressure in an American community. The Beaver Dam Eye Study. AB - The Beaver Dam Eye Study is a population-based study of age-related eye diseases in persons 43-86 yr of age. Applanation tonometry was done on all study subjects. Mean intraocular pressure (IOP) increased significantly with age. Mean IOP differed little between the sexes and was not significantly different after age adjustment (in right eyes of 2721 women, it was 15.5 mm Hg, and in right eyes of 2135 men, it was 15.3 mm Hg). There was an association of IOP with systolic and diastolic blood pressures, body mass index, hematocrit, serum glucose, glycohemoglobin, cholesterol level, pulse, nuclear sclerosis, season, and time of day of measurement. These data confirm that, in a general population, IOP is associated with important systemic and ocular characteristics. Those characteristics should be considered in further research on determinants of IOP. PMID- 1607233 TI - Isocapnia blocks exercise-induced reductions in ocular tension. AB - Previous reports suggest that isometric exercise (2-min handgrip at 50% maximal voluntary contraction [MVC]) substantially lowers intraocular pressure (IOP). The authors questioned whether the mechanism for lowered IOP in exercise is secondary to hyperventilation. Accordingly, in this study 11 subjects, with elevated IOP (greater than or equal to 18 mm Hg) and otherwise healthy, did 2 min of handgrip exercise at 50% MVC with and without carbon dioxide supplementation to maintain isocapnic conditions. Compared with a control experiment that involved neither exercise nor CO2 addition, exercise induced a fall in IOP from 18.3 to 15.6 mm Hg (P less than 0.001). This statistically significant decline in IOP persisted for 15 min after the exercise session. At the point of minimum IOP (1 min after the end of exercise), the minute ventilation was elevated from 6.5-8.1 l/min (P less than 0.05), and the end-tidal partial pressure of CO2 (PCO2) was reduced from 37.0 to 33.7 mm Hg (P less than 0.05) with respect to control values. By contrast, adding CO2 sufficient to maintain isocapnic conditions (experimental end-tidal PCO2 = 38.9 versus 38.5 mm Hg in the control study; P = not significant) abolished the exercise-induced ocular hypotension (experimental IOP = 17.8 versus 18.1 mm Hg in the control study; P = not significant). It was concluded that prevention of hypocapnia during isometric handgrip exercise blocks the subsequent fall in IOP, suggesting both that isometric exercise per se has no direct influence on IOP and that therapy for ocular hypertension could involve manipulation of blood gases. PMID- 1607234 TI - Effects of timolol, betaxolol, and levobunolol on human tenon's fibroblasts in tissue culture. AB - Evidence has been found suggesting that long-term therapy with topical antiglaucoma medications may decrease the success of glaucoma filtering surgery. To investigate this question further, the antiproliferative effects of the preservative benzalkonium chloride and three pure and commercially available beta adrenergic antagonist preparations (timolol, betaxolol, and levobunolol) were studied on tissue cultures of human Tenon's capsule fibroblasts. Each drug preparation was tested on three different cell lines. Fibroblast growth was measured with tritiated thymidine uptake and hexosaminidase assays. Trypan blue uptake was used to assess cell viability microscopically. The commercially available preparations containing benzalkonium chloride and those of betaxolol and levobunolol without the preservative had similar inhibitory doses for 50% of cells. The timolol preparation without preservative was significantly less toxic than its commercially available one. The three tested beta-adrenergic blockers did not stimulate fibroblast proliferation directly in this in vitro model. Even when the cultures were washed free of the drugs, growth continued to be suppressed, suggesting that the inhibition was not reversible. An increase in fibroblasts and inflammatory cells after long-term antiglaucoma medical therapy thus may be caused not by a direct stimulation of cell proliferation but by chronic inflammation from the irritating effects of antiglaucoma medications and/or their preservatives. PMID- 1607235 TI - The effects of dexamethasone on fibronectin expression in cultured human trabecular meshwork cells. AB - Topical administration of glucocorticoids to the eye can lead to the development of ocular hypertension. This increase in intraocular pressure is caused by the heightened resistance to flow of aqueous humor from the eye, presumably at the trabecular meshwork (TM). This study reports the effects of dexamethasone (DEX) on the expression of the extracellular matrix protein fibronectin (FN) in cultured human TM cells (HTM). The expression of FN was evaluated in four HTM cell strains by epifluorescence microscopy and immunoblotting and autofluorography of electrophoretically separated cell proteins. There was a heterogeneous response of the four cell strains tested. Treatment of cell strain HTM4 with DEX (10(-7) mol/l) for 17 d caused an approximate doubling of cell associated and secreted FN. This DEX-induced increase in FN expression was progressive after the first 7 d of treatment and was blocked partially with a glucocorticoid antagonist, cortexolone. By contrast, DEX treatment induced an intermediate 50-60% increase in FN expression in cell strains HTM10 and HTM2; in HTM6, FN was unchanged after exposure to the glucocorticoid. This model system may be useful to examine molecular changes associated with corticosteroid-induced ocular hypertension and evaluate glaucomatous changes in the TM because increased FN deposition occurs in the aqueous humor outflow pathway of patients with open angle glaucoma. PMID- 1607236 TI - Optic nerve head microvasculature of the rabbit eye. AB - Vascular luminal castings of rabbit eyes were microdissected and studied with scanning electron microscopy to elucidate the three-dimensional angioarchitecture of the optic nerve head. Using sequential microdissection, an incomplete arterial circle was identified as terminal branches of two to three short posterior ciliary arteries around the optic nerve head. Several recurrent branches from the arterial circle form a pial arterial network. This pial system supplies the optic nerve head microvasculature and receives numerous venules from them. The only large vessel to enter the optic nerve is a central retinal artery that has few branches within the optic nerve and provides several branches at the surface of the optic disc. Moderately numerous vessels connect the retinal and ciliary vascular layers within the optic nerve head. Few arterioles to the optic nerve head arise from the choroid; however, there are a small number of capillary and numerous venous connections between them. These results indicate that the principal blood supply of the rabbit optic nerve head is derived from the short posterior ciliary arteries by the arterial circle. The retinal arteries contribute to the surface vasculature of the optic nerve head. The pial system also plays a significant role in both supply and drainage of the rabbit optic nerve head. PMID- 1607237 TI - Whole-cell currents from noncultured human lens epithelium. AB - Perforated patch techniques were used to measure whole-cell ionic currents in freshly dissociated human lens epithelial cells that had not been subjected to culture media or serum. With a 150 mmol/l K+ internal solution, the cells had resting voltages of -27.4 +/- 4.7 mV (mean +/- standard deviation [SD]) and capacitances of 10.4 +/- 2.8 pF (mean +/- SD). The input resistance of the cells was 1.6 +/- 0.7 G omega (mean +/- SD) at large negative voltages. A delayed outwardly rectifying K+ current was found in most cells studied. Current magnitudes of 1-2 nA at +80 mV were common. The current had selectivities, activation time constants, deactivation time constants, open probability versus voltage relationships, and inactivations similar to those of the delayed rectifying K+ current found in many cell types and studied previously in cultured human lens epithelium. These results verify the existence, at high density, of these currents in noncultured human epithelial cells. PMID- 1607238 TI - The age of rats affects the response of lens epithelial explants to fibroblast growth factor. An ultrastructural analysis. AB - Fibroblast growth factor (FGF) is a potent inducer of fiber differentiation in lens epithelial explants from neonatal rats as assessed by the accumulation of fiber-specific proteins (beta- and gamma-crystallins) and the progression of cells through a sequence of morphologic events characteristic of fiber differentiation in situ. Because new fibers normally are formed in the lens throughout life, the authors questioned whether epithelial cells from rats of all ages are induced to differentiate into fibers by FGF. Earlier studies have shown that, with the increasing age of the donor rat, the lens epithelial explants had a reduced ability to accumulate beta- and gamma-crystallins in response to FGF. To determine if the characteristic morphologic events in fiber differentiation were induced by FGF in explants from rats of different ages, an ultrastructural study was done. Using the time of appearance and level of expression of the following morphologic markers of fiber differentiation: (1) cell elongation, (2) reduction of cytoplasmic organelles, (3) formation of cell processes, and (4) fiber denucleation, the level of fiber differentiation induced by FGF was assessed in explants from 10-, 21-, 100-, and 175-day-old rats. These results showed that, with increasing donor age, epithelial cells showed a gradual decline in responsiveness to FGF. This was manifested by a slower progression through the sequence of fiber-specific structural events as the age of the donor rat increased. At all ages studied, cells in the central region of explants responded more slowly than cells from the peripheral region. The finding that FGF induces events in fiber differentiation, albeit at a slower rate, in explants from mature rats supports the hypothesis that FGF in the eye continues to play a role in inducing lens epithelial cells at the lens equator to differentiate into fibers throughout life. PMID- 1607239 TI - Lens regeneration in juvenile and adult rabbits measured by image analysis. AB - Secondary cataract growth commonly occurs after extracapsular cataract extraction. The proliferation of this regrowth occurs at rates related to many factors. In this study, the authors analyzed the amount of lens regeneration after endocapsular lens extraction that leaves the anterior and posterior capsules relatively intact. The analysis was performed in New Zealand albino rabbits with the aid of image analysis measurements in young and adult animals. The effect of low vacuum suction of the anterior capsule on the growth was determined. Lens regeneration was used as a measure of the growth potential of the leftover epithelial cells in the capsule bag. The results showed that lens regeneration was significantly faster in younger rabbits. However, low vacuum suction had no effect on the growth rate. Potential therapeutic agents for preventing secondary cataracts may be better analyzed with image analysis processing of lens regeneration, a precise and rapid measurement technique. PMID- 1607240 TI - Human meibomian glands: the ultrastructure of acinar cells as viewed by thin section and freeze-fracture transmission electron microscopies. AB - Heightened interest in meibomian glands dysfunction prompted the authors to examine the ultrastructure of the glandular epithelium in specimens of surgical origin, by thin section and freeze-fracture electron microscopies. In meibomian glands, the morphology and ultrastructure of acinar cells varies considerably according to their stage of holocrine differentiation. This study shows close interdependence between fat droplets and Golgi apparatus or endoplasmic reticulum. As the cells initiate their differentiation, the smooth endoplasmic reticulum and the Golgi apparatus become prominent and the first small lipid droplets appear in the cytoplasm. When fractured through a plane close to their surface, lipid droplets appear onion-like structured, ie made up of a variable number of irregular shaped concentric lamellae. This lamellar organization suggests that membranes are not only involved in synthesis, but also that some of their components are incorporated in the fat droplets. The authors conclude that human meibomian glands are a holocrine glandular complex that, despite great differences in type and location, present basic similarities with sebaceous glands. PMID- 1607241 TI - Inhibition of human subconjunctival fibroblast proliferation by immunotoxin. AB - The ability to target proliferating cells is important for agents used to modulate wound healing by decreasing the growth of fibroblasts. Proliferating cells are known to express increased numbers of transferrin receptors and have increased receptor turnover. 454A12 Mab-rRA, an immunotoxin containing anti-human transferrin receptor monoclonal antibody conjugated to recombinant ricin A chain, was shown to inhibit the proliferation of human subconjunctival fibroblasts in vitro. A dose-related reduction of cell counts was observed in proliferating cells. More than 90% inhibition was achieved with an immunotoxin concentration of 10 ng/ml per 20,000 cells plated. In contrast, confluent fibroblasts were markedly less sensitive to the immunotoxin at equivalent concentrations. Comparative experiments demonstrated that 5-fluorouracil has less specificity for proliferating cells, with significant death of confluent fibroblasts at high drug concentrations. PMID- 1607242 TI - Effect of intraocular gamma-interferon on immunoregulatory properties of iris and ciliary body cells. AB - Resistance of the anterior chamber (AC) of mouse eyes to expression of cell mediated immunity can be overcome by pre-treating the eye with a dose of recombinant rat gamma-interferon (gamma IFN) that is of itself noninflammatory. To study the mechanism of this form of intraocular inflammation, cells of the tissues surrounding the AC (iris, ciliary body, cornea) were studied in vivo for alterations in phenotype and in vitro regarding their effects on antigen-driven T cell activation. The results indicate that gamma IFN: (1) induced class II major histocompatibility complex (MHC) expression on resident bone marrow-derived cells of iris and ciliary body (I/CB), but not the cornea; (2) led to recruitment of bone marrow-derived cells into the I/CB stroma; and (3) failed to induce class II MHC expression on ocular epithelial cells. Cell suspensions prepared from gamma IFN-treated I/CB superficially resembled normal I/CB cells in that neither were able to activate allogeneic T cells and both were able to suppress antigen-driven T cell activation in vitro. However, unlike cells from normal eyes, I/CB cells from gamma IFN-treated eyes suppressed T cell activation primarily through the secretion of prostaglandins. These results indicate that the ability of gamma IFN treated eyes to display immunogenic inflammation probably does not result merely from the restoration of conventional antigen presenting cells to this environment, but appears to correlate with a critical change in the molecular mediators of immunosuppression. The findings are discussed in terms of the possibility that the eye may be able to respond to abrogation of its primary immunosuppressive microenvironment by erecting a secondary microenvironment that also is capable of suppressing immunogenic inflammation with a different set of antiinflammatory mediators. PMID- 1607243 TI - Sensitivity to temporal luminance modulation in congenital nystagmus. AB - Uniform field temporal contrast sensitivity functions were compared for 10 subjects with congenital nystagmus (seven idiopathic, three with albinism) and 10 normal observers. Sensitivity to luminance modulation did not differ significantly from normal at any temporal frequency tested except 0.5 Hz, at which the subjects with nystagmus had slightly higher sensitivity. In conjunction with other recent findings, their essentially normal temporal contrast sensitivity suggests that persons with nystagmus process retinal information continuously, rather than selectively during only only one phase of the nystagmus. PMID- 1607244 TI - The repeatability of measurement of the ocular components. AB - Studies of the ocular components of refraction typically neglect issues of repeatability of measurement methods or analyze method comparison/repeatability data inappropriately using correlation. The authors have examined the repeatability of refractive error measures (retinoscopy, subjective refraction, and Canon R-1 autorefraction, noncycloplegic and cycloplegic), axial dimension measures (Allergan-Humphrey A-scan ultrasound), and corneoscopy (keratometry and KERA photokeratoscopy), and the agreement between different refractive error and corneal measurement methods on 40 pre-presbyopic normal adults. The authors plotted the difference versus the mean of two different measurement occasions (repeatability), or two different methods (agreement), to determine the bias (mean of the differences relative to zero) and 95% limits of agreement of each technique. The most reliable measure of refractive error was autorefraction with cycloplegia, with 95% limits of agreement of +/- 0.32 diopters. Cycloplegic autorefraction had no statistically significant bias compared to cycloplegic subjective refraction. Cycloplegic retinoscopy was the least reliable refractive error measure, with repeat measures on two separate occasions extending over 95% limits of agreement of +/- 0.95 D. Anterior chamber depth was reliable to +/- 0.29 mm, lens thickness to +/- 0.20 mm, and vitreous chamber depth to +/- 0.37 mm. Corneal curvature measures show keratometry to be more reliable (to +/- 0.87 D) than photokeratoscopy (+/- 2.02 D) with a statistically significant bias (paired t-test, P less than 0.0001) of 0.57 D flatter for photokeratoscopy. PMID- 1607245 TI - Study of the polyol pathway and cell permeability changes in human lens and retinal pigment epithelium in tissue culture. AB - The polyol pathway was investigated in primary cultures of human retinal pigment epithelial (HRPE) cells and the results were compared with those in human lens epithelial (HLE) cells cultured under similar conditions. Significant levels of galactitol were formed in HRPE cells cultured for 72 hr in a medium containing 30 mmol/l D-galactose. Polyol accumulation was accompanied by the appearance of vacuoles as seen by transmission electron microscopy (TEM). Biochemical analysis revealed a significant depletion of cellular myoinositol, taurine, and a number of other free amino acids similar to those in HLE cells. These morphologic and biochemical changes observed in HRPE cells cultured in high galactose medium were inhibited or prevented by the inclusion of an aldose reductase inhibitor in the medium, further supporting the view that vacuole formation is due to the osmotic effect of polyol formation mediated by aldose reductase. The similarity of intracellular vacuole formation resulting from polyol accumulation and the biochemical changes in HRPE and HLE cells strongly suggests that a common mechanism is involved. PMID- 1607246 TI - Nitric oxide and endothelin-1 are important regulators of human ophthalmic artery. AB - The vascular endothelial cells have the ability to modulate local vascular tone by releasing relaxing factors such as nitric oxide or the vasoconstrictor peptide endothelin-1. Although this regulatory system is found in all vertebrates, there is a great heterogeneity in the release of these endothelium-derived substances, from one organ to an other, between large and small vessels, and between different species. Therefore, observations made in certain vascular beds or animals do not necessarily apply to human ophthalmic circulation. The present study was designed to investigate endothelial mediators in the human ophthalmic artery. The results show that in the human ophthalmic artery, nitric oxide is released under basal conditions and that its production can be markedly stimulated by bradykinin, acetylcholine, and particularly histamine, which cause profound vascular relaxation. In contrast, endothelin-1 evoked potent contractions, which were unaffected by the calcium antagonist nifedipine. However, upon re-exposure of the blood vessels to the peptide, marked tachyphylaxis occurred. These findings demonstrate that in the human ophthalmic artery, endothelium-derived nitric oxide and endothelin are very potent modulators of vascular tone, suggesting that they play an important role in the regulation of local blood flow in the eye. Hence, endothelium dysfunction may represent a new pathogenetic mechanism in disease states associated with altered blood flow to the eye, such as diabetes, hypertension, and some forms of low tension glaucoma. PMID- 1607247 TI - Liposome suppression of proliferative vitreoretinopathy. PMID- 1607248 TI - An efficient multiple-exposure analysis of the toxicity of crisnatol, a DNA intercalator in phase II clinical trials. AB - To investigate the toxicity and mechanism of action of crisnatol (CRS), a new DNA intercalator currently in phase II clinical trials, we analyzed cellular and nuclear flow cytometric (FCM) parameters of murine erythroleukemic cells (MELC) exposed to a range of CRS concentrations over three exposure conditions: short term (4 h), long-term (24 h), and short-term with recovery (4 h+/19 h-). At 0.5 1.0 microM CRS, 4 h exposure results in a reversible G2-phase block, while 24 h exposure results in greater than G2 polyploidy. At 5-10 microM CRS concentrations, cells exhibit persistent retardation of S-phase progression or irreversible G2 and/or greater than G2 blocks, depending on duration of exposure. Cells terminally blocked in G2 exhibit increased nuclear/cellular volumes and increased nuclear fluorescein isothiocyanate (protein) staining, suggestive of unbalanced growth. At 25-50 microM CRS concentrations, MELC exhibit severe membrane perturbation (loss of viability) regardless of exposure. In contrast, following similar exposures to an inactive isomer of CRS, MELC exhibit minimal cell cycle effects, suggesting that cell cycle kinetics may be a useful criterion for assessing potential efficacy. Similar analyses with different classes of chemotherapeutic agents reveal that the range of induced cellular/nuclear perturbations varies with the class of compound used. Taken together, these results suggest that drug toxicity can vary with both concentration and duration of exposure and, as such, a selective multiple-exposure FCM analysis may better represent the spectrum of drug action for drug development and pharmacodynamic studies. PMID- 1607249 TI - Activity of a recombinant transforming growth factor-alpha-Pseudomonas exotoxin hybrid protein against primary human tumor colony-forming units. AB - Transforming growth factor-alpha-Pseudomonas exotoxin-40 (TP40) is a recombinant fusion protein. TP40 consists of the entire human transforming growth factor alpha (TGF alpha) protein fused to a 40,000 Da. segment of the Pseudomonas exotoxin A protein. TP40 is a bifunctional molecule that possesses the epidermal growth factor (EGF) receptor binding properties of TGF alpha and the cell killing properties of Pseudomonas exotoxin A. These properties make TP40 a selective cytotoxic agent that kills EGF receptor bearing cells. TP40 has been shown to effectively kill human tumor cell lines that possess EGF receptors in vitro and in nude mice. In the present study, TP40 was tested against tumors taken directly from patients and grown in a soft agar human tumor cloning system. A total of 107 patients' tumors (taken from patients with tumors refractory to chemotherapy) were tested with a continuous exposure to 0.5-50 nM concentrations of the agent. TP40 exhibited a clear dose response effect against a wide variety of human solid tumor colony-forming units with greater than or equal to 84% of evaluable tumors responding at a drug concentration greater than or equal to 24 nM. When used as a continuous exposure, concentrations of TP40 as low as 5 nM demonstrated substantial in vitro activity. This activity included cytotoxicity against breast, colorectal, endometrial, head and neck, non small-cell lung, gastric, sarcoma, and pancreatic cancer tumor colony-forming units. Additional in vivo testing of this compound is warranted. PMID- 1607251 TI - Echinomycin (NSC 526417) in recurrent and metastatic squamous cell carcinoma of the cervix. A phase II trial of the Gynecologic Oncology Group (GOG). AB - Nineteen evaluable patients with recurrent or metastatic squamous cell carcinoma of the uterine cervix were treated with 1,500 micrograms/m2 of echinomycin every 4 weeks. No patient had received prior chemotherapy. There was one partial response (5% response, 95% confidence interval for response of 0% to 26%). The major toxicity was nausea and vomiting which was moderate to severe in six patients. Myelosuppression was not observed. Echinomycin, in this dose and schedule displays no major activity in chemotherapy-naive patients with advanced squamous-cell carcinoma of the cervix. PMID- 1607250 TI - Phase II trial of didemnin-B in advanced epithelial ovarian cancer. A Southwest Oncology Group study. AB - A Phase II study of Didemnin-B, a marine cyclic depsipeptide, was undertaken in patients with progressive epithelial ovarian cancer. The starting dose was 2.6 mg/m2. Fifteen patients received the drug, of whom twelve were evaluable. There were no responses observed in the twelve patients. The two most frequent toxicities were nausea and vomiting and anemia. On the basis of this trial, Didemnin-B is not felt to have significant effect with epithelial ovarian cancer. PMID- 1607252 TI - Phase II study of 10-EdAM in patients with squamous cell carcinoma of the head and neck, previously untreated with chemotherapy. AB - Fifteen patients with advanced head and neck cancer not curable with radiation or surgery were entered into a phase II study of 10-EdAM. None of the patients had received prior chemotherapy. 10-EdAM was administered intravenously at a dose of 80 mg/m2 each week. Four patients were not eligible for evaluation. Two died before completing four cycles of chemotherapy, one refused further treatment and one developed hepatic toxicity resulting in withdrawal. Of the remaining patients, three had a partial response. The major toxicities were leukopenia and mucositis. PMID- 1607254 TI - Phase II evaluation of didemnin B in advanced adenocarcinoma of the kidney. A Southwest Oncology Group study. AB - The Southwest Oncology Group studied the response rate and toxicity of didemnin B (3.47 mg/m2 i.v. q 28 days) in patients with advanced renal cell carcinoma. There were no responses in 22 response evaluable patients. Toxicity was significant with 10 patients having grade 3 or 4 toxicity. Toxicity seen included nausea and vomiting, exacerbation of coronary artery disease, hyperglycemia, anorexia, diarrhea and hepatitis. Didemnin B was toxic but inactive in patients with renal cell treated at this dose. PMID- 1607253 TI - Evaluation of deoxycoformycin in patients with advanced renal cell carcinoma. An ECOG pilot study. PMID- 1607255 TI - Insights on the radiologic centennial--a historical perspective. Roentgen and the "new light". I. Roentgen and Lenard. PMID- 1607256 TI - Arterial response to ketanserin and aspirin in patients with advanced peripheral atherosclerosis. AB - BACKGROUND: In advanced atherosclerosis, endothelial lesions and turbulent flow in stenotic vessels result in platelet aggregation with the liberation of vasoactive factors, including thromboxane A2 and serotonin. This study was designed to assess the combined effect of these factors on arterial dimensions at the time of limb angiography in patients with advanced peripheral vascular disease. METHODS: Diameter changes of 53 segmental stenosis of large arteries were measured in digitized angiograms by a computerized objective method in response to either placebo (13 segments in 7 patients), ketanserin (23 segments in 23 patients), or ketanserin superimposed on aspirin (17 segments in 7 patients). Responses of arterial collaterals were evaluated by a coded assessment. Statistically significant vasodilatation was observed in both the stenotic and post-stenotic segments of the large arteries only when serotonin-2 receptor blockade with ketanserin and cyclo-oxygenase inhibition with aspirin were combined. RESULTS: In the area of the stenosis and in the post-stenotic segment diameter increased 8.2% +/- 2.3% (P = .032) and 7.3% +/- 1.3% (P less than .001), respectively, when aspirin was combined with ketanserin. Significant changes did not occur in either the placebo group or in the group receiving only ketanserin. In the area of stenosis, there was a good correlation between the relative baseline narrowing of the vessel and its vasodilatation after combined ketanserin and aspirin (r = .689; P = .002). Vasodilatation at the level of arterial collaterals also was significantly more pronounced when the combination was used (P less than .001). CONCLUSIONS: These findings suggest a component of vasoconstriction related to the deposition of activated platelets in stenotic segments of the large arteries in atherosclerosis. PMID- 1607257 TI - Characterization of cerebral infarction by multicomponent analysis of transverse magnetization decay curves. AB - RATIONALE AND OBJECTIVES: Individual components of the transverse magnetization decay curve (TDC) were assessed for their ability to characterize ischemia in photochemically induced cerebral infarcts. METHODS: Fifty rats were randomly divided into equal-sized experimental and control groups, which were subdivided into groups studied at five different time points, ranging from 6 hours to 22 days. All the rats received transcalvarial irradiation with 560-nm light. Five rats in each time group also received a sensitizing dye before irradiation. In these latter animals, lesions of uniform size and location developed. Lesions were compared with tissue of similar volume and location from the contralateral cortex of the experimental animals and with tissue from both hemispheres of the control animals. TDCs of all the samples were measured and fit with mono- and bi exponential functions. RESULTS: Unlike the control tissue, infarcted tissue displayed definitive two-component TDC behavior. The time course of the bi exponential parameters yielded information unavailable from mono-exponential analyses. CONCLUSIONS: Bi-exponential analysis of TDCs may have diagnostic use as a more sensitive indicator of cerebral infarction than mono-exponential analyses. PMID- 1607258 TI - Pulmonary scintigraphy in elastase-induced emphysema in pigs. Correlation with high-resolution computed tomography and histology. AB - OBJECTIVES: The objective of this study is to evaluate the mild physiologic changes of elastase-induced pulmonary emphysema in the pig by radionuclide scintigraphy and to correlate these findings with high-resolution computed tomography (HRCT) and histologic examination. METHODS: Eight 7- to 12-week-old Yorkshire pigs were studied. Perfusion and ventilation studies were performed in six pigs at 1- or 2-week intervals after elastase instillation. HRCT was simultaneously performed for correlation with radionuclide scintigraphy. For the perfusion scans, technetium 99m (99mTc) macroaggregated albumin (MAA) was used, and both planar and single-photon emission CT (SPECT) images were obtained. Ventilation studies were performed with xenon-133 gas with dynamic sequential imaging. RESULTS: Histopathologic findings demonstrated dilatation and destruction of the alveoli and were similar to those previously reported by the authors. The SPECT perfusion images showed significantly impaired perfusion of the involved segment of the lung, corresponding to the region where elastase was instilled. The planar xenon-133 ventilation scintigraphy did not show abnormal air trapping. The mild emphysema induced with elastase manifested as decreased and impaired perfusion with no detectable ventilation abnormalities. The sensitivity of SPECT perfusion studies for the detection of the mild changes of elastase-induced pulmonary emphysema were higher than that of HRCT. CONCLUSIONS: The perfusion studies reflect functional or physiologic changes in contrast to structural changes seen on HRCT. This pig model was valuable to study the scintigraphic manifestation of elastase-induced pulmonary emphysema. PMID- 1607259 TI - Quantitative assessment of myocardial enhancement with iodinated contrast medium in patients with ischemic heart disease by using ultrafast x-ray computed tomography. AB - BACKGROUND AND RATIONALE: The authors report the quantitation of myocardial enhancement using iodinated contrast medium in patients with ischemic heart disease. Twenty-eight patients with chronic ischemic heart disease and 11 controls were examined by ultrafast computed tomography (CT) using 100-msecond scans. METHODS: The authors analyzed M/L (ratio of post-contrast incremental increases in the left ventricular myocardial and luminal CT number) in early and late phases after contrast injection. RESULTS: In controls, mean values of early and late M/L were 30% and 51%, respectively. In infarcted or severely ischemic segments, early M/Ls (19%, 16%) were significantly small (P less than .001), whereas late M/Ls (90%, 63%) were higher (P less than .001, .01) than controls. Segments with infarction or severe ischemia were differentiated from mild or nonsignificant ischemia by using this parameter (sensitivity, 99%; specificity, 88%). CONCLUSIONS: M/L is useful for detection of the ischemic myocardium. PMID- 1607260 TI - Normal renal blood flow measurement using phase-contrast cine magnetic resonance imaging. AB - RATIONALE AND OBJECTIVES: This study assesses the ability of a cardiac-gated phase-contrast magnetic resonance imaging (MRI) technique to measure renal blood flow (RBF) noninvasively in humans. METHODS: In nine normal volunteers, total RBF in the renal arteries and in the left renal vein was estimated by MRI and correlated with RBF determined by the clearance of para-aminohippuric acid (CPAH) and the hematocrit level. RESULTS: Correlation of RBF estimated from left renal vein flow, with RBF by CPAH-hematocrit, yielded r = .86 (P less than .003). Repeated measurement of RBF by MRI demonstrated a high degree of reproducibility, with coefficients of variation ranging from 4.8% to 8.9%. However, the MRI measurements of arterial flow did not significantly correlate with the standard measurements. CONCLUSIONS: Reproducible noninvasive measurement of normal RBF is possible with the phase-contrast MRI technique used to measure renal venous blood flow. PMID- 1607261 TI - Potential usefulness of computerized nodule detection in screening programs for lung cancer. AB - RATIONALE AND OBJECTIVE: To alert radiologists to possible nodule locations and subsequently to reduce the number of false-negative diagnoses, the authors are developing a computer-aided diagnostic (CAD) scheme for the detection of lung nodules in digital chest images. METHODS: A computer-vision scheme was applied to photofluorographic films obtained in a mass survey for detection of asymptomatic lung cancer in Japan. Ninety-five patients with abnormal test results who had primary and metastatic lung cancers and 103 patients with normal test results were included. RESULTS: The sensitivity of the computer output was comparable with that of physicians in this mass survey (62%). The computer detected approximately 40% of all nodules missed in the mass survey, but missed 17 true positive results identified in the mass survey. The CAD scheme produced an average of 15 false-positive findings per image. CONCLUSION: If the number of false-positive results can be significantly reduced, computer-vision schemes such as this may have a role in lung cancer screening programs. PMID- 1607262 TI - Diagnostic image use by nonradiologist lecturers in an introductory clinical medicine course. AB - RATIONALE AND OBJECTIVES: A curriculum-tracking study was designed to determine the type and amount of diagnostic imaging used by nonradiologists teaching an Introduction to Clinical Medicine (ICM) course to second-year medical students. METHODS: Two second-year medical students independently recorded the type and number of images shown, the length of the lecture, the departmental affiliation of the lecturer, and the amount of time devoted to either didactic radiology or radiologic images during each of 288 lectures in the 1990 ICM course. RESULTS: A total of 35.2% of the lectures presented some type of diagnostic image, and 7.0% of all lecture time was devoted to radiology. No mammography or diagnostic nonangiographic interventional images were shown. CONCLUSIONS: The results suggest that a more consistent and uniform presentation of diagnostic images across disciplines is required, emphasizing the need for more coordination of radiology instruction through consultation with the Department of Radiology. PMID- 1607263 TI - Training radiologists for the future. The oversupply of physicians, subspecialization, and turf. PMID- 1607264 TI - A methodologic overview of the evaluation of costs and benefits in diagnostic radiology. PMID- 1607265 TI - Acute appendicitis in children: an evaluation with ultrasound. PMID- 1607266 TI - Influence of different counterions on the fluorescent probe-DNA complex. AB - Studies carried out on both linear and covalently closed DNA have clearly revealed at least two different types of probe-DNA complexes depending on the different experimental procedure adopted, and two main types of binding of the probe have been clearly established and referred to as intercalative and external binding. In order to investigate the influences of the different counterions on the stability of the probe-DNA complex, a set of static fluorimetric measurements were performed in a wide range of concentrations (1 mM to 2 M) of different alkaline-earth chlorides. At low salt concentrations (in the range of millimolar values) no detectable fluorescence intensity changes were evidenced by the use of alkaline salts, but a marked decrease was detected by using alkaline-earth salts. The present work investigates moreover the role played by the different salt, in first place Calcium salts, on the stability of ethidium-DNA complex, by the use of the static fluorimetric titration procedure which is able to discriminate between the two strong and weak binding sites on DNA. Our experimental results have been interpreted in terms of a peculiar Calcium-DNA interaction, involving not only the electrostatic charges of phosphate moiety but also the aromatic rings of the bases, i.e., the intercalation sites on double helix DNA. PMID- 1607267 TI - The phosphorylation of nuclear proteins in normal and transformed cells. AB - Normal (Rat 1) and transformed cells (middle T antigen-transformed derivative 3C3) were grown in the presence of 32P-orthophosphate. 32P-labelled nuclear proteins were fractionated by means of two-dimensional gel electrophoresis and detected by autoradiography. The comparative analysis of the autoradiographs of the normal and transformed cells revealed differences in the phosphorylation patterns of histone and low-molecular-mass high mobility group proteins (HMG). Three of the HMG proteins were highly phosphorylated in the transformed cells, and the analysis of their phosphorylation sites showed that these HMG proteins were phosphorylated on serine and threonine but not on tyrosine residues. PMID- 1607268 TI - The epidemiology of injuries sustained by Israeli troops during the unrest in the territories administered by Israel, 1987-89. AB - Information on 1,267 Israeli soldiers injured in the administered territories (West Bank and Gaza) between December 1987 and November 1989 as a result of the Palestinian unrest was retrieved by us. The cases were divided according to cause, body location and severity of the injury. Most of the injuries were caused by stones (62%), the head being the primary site of injury (50.3%). Although the majority of injuries were light (92.3%), there was a 1.1% fatality rate. Enforcement of orders requiring troops to use protective gear that is issued to them would reduce the number and severity of the injuries. PMID- 1607269 TI - Evaluation of clinic blood pressure measurements: assessment by daytime ambulatory blood pressure monitoring. AB - The clinical value of a set of three clinical blood pressure measurements as a predictor of daytime ambulatory hypertension was assessed by performing a set of clinical blood pressure measurements in 171 borderline hypertensives, and calculating their diagnostic accuracy, sensitivity, specificity and predictive value compared to the daytime average of ambulatory blood pressure monitoring. Diagnostic accuracy was 0.63, sensitivity was 81% and specificity was 47%. Positive and negative predictive values were 0.60 and 0.74, respectively. The set of clinical measurements detected 81% of hypertensives, but 36% of the population screened was mislabelled--48 patients (28%) as hypertensive and 15 (8%) as normotensive. A single set of clinic blood pressure measurements is quite sensitive for diagnosing daytime hypertension, although its accuracy, specificity and predictive value are low. The subpopulation incorrectly labelled as normotensive may have a different prognosis and merits further prospective study. PMID- 1607270 TI - Hypothalamic etiology in sympathetically induced pathogenic cardiovascular changes in the cat. AB - Transient cardiovascular changes, including angina-like electrographic signs, are inducible by electrical stimulation of discrete sites in the prefornical region of the lateral hypothalamus (LH) of cats. Repeated stimulation may result in neurogenic cardiac infarction and myocardial bleeding. Thirty Swiss breed locally grown cats were studied under alpha-chloralose anesthesia in pairs, one as control and one experimental, with only the latter receiving multiple stimulations. ECG in lead II and arterial blood pressure were recorded on a Grass polygraph (USA). Electrical stimulation was delivered to a LH target at Fr 9.0, L2.5, D-1 to -2, by means of stainless steel wire electrodes. Stimulation consisted of 15-sec trains of square wave pulses at 100 Hz, 0.2-0.5 msec duration, and threshold currents of 0.05-0.1 mAmp. Stimulation at these LH sites induced small blood pressure changes, often with a small increase or no change in heart rate, presumably a manifestation of baroreceptor dysfunction. Repeating this stimulation greater than 6 times was shown to be pathogenic: on gross examination a darkened area was seen, mostly on the upper ventricular surface of the heart. Microscopic examination of such sites revealed subendocardial bleeding and sometimes also microinfarcts. Scanning electron microscopy revealed an unusually large number of contractures of the myofilaments. Biochemical analysis showed diffusion of catecholamines from nerves. Total myocardial blood flow increased following such stimulation, proportional to the stimulus intensity. It is pointed out that this is not contradictory to the sharply localized ischemic changes assumed to be responsible for the cardiopathy. PMID- 1607271 TI - Risk factors and their effect on the results of Burch colposuspension for urinary stress incontinence. AB - Forty patients with urinary stress incontinence were studied and the results of Burch colposuspension evaluated. Combined detrusor instability and stress incontinence were found in 22.5% of the patients. The results of surgery showed that 87.5% of the patients (35/40) were cured of incontinence. None of the contributing risk factors of incontinence had a significant role in the outcome of surgery. In view of this, all patients with surgically amenable urinary incontinence should be considered for surgical resolution of this condition. PMID- 1607272 TI - Bioequivalence of quinidine in two sustained-release preparations. AB - The bioequivalence of two sustained-release preparations of quinidine bisulphate from Teva (Israel) and from Astra (Sweden) was assessed in an acute, single-dose randomized cross-over study in seven healthy subjects. There was no significant difference in time to peak, peak serum concentration, area under the concentration time curve from 0 to infinity, and the fraction absorbed between quinidine bisulphate 500 mg from Teva and from Astra. In addition, quinidine bisulphate 250 mg from Teva was compared with the short-acting quinidine sulphate 200 mg. The quinidine bisulphate from Teva had a significantly P less than 0.025) decreased peak serum concentration and an increased time to peak compared with the short-acting quinidine sulphate, although these two drugs are similar for the area under the curve from 0 to infinity. Our pharmaceutical records show that 85% of outpatients receiving quinidine are given the sustained-release quinidine bisulphate. However, only 36% of the outpatients prescribed sustained-release quinidine bisulphate are appropriately prescribed for twice-daily treatment. Thus the quinidine bisulphate from Teva is a sustained-release preparation with bioequivalence to the reference sustained-release preparation and can be administered twice daily. PMID- 1607273 TI - Pneumococcal empyema following endoscopic sclerotherapy in a child with cavernous transformation of the portal vein. AB - Esophageal sclerotherapy is widely used in the treatment of bleeding esophageal varices. Complications vary from chest pain to esophageal perforation. Our patient, suffering from cavernous transformation of the portal vein, developed massive empyema following sclerotherapy. Although small asymptomatic pleural effusions have been reported, massive empyema requiring surgical drainage, without evidence of esophageal perforation, has, to our knowledge, not been described. PMID- 1607274 TI - Cryotherapy--primary treatment of genital condylomata. PMID- 1607276 TI - Replication of enteroviruses in human mononuclear cells. PMID- 1607275 TI - Screening for Wilson's disease in the investigation of hematuria. PMID- 1607278 TI - Cryotherapy in genital Condylomata acuminata. PMID- 1607277 TI - Injuries sustained by Israeli soldiers during the "Intifada"--1987-89. PMID- 1607280 TI - Multiphasic screening: an idea whose time has passed. AB - The theory of screening for preclinical disease requires that early diagnosis and treatment will lead to an outcome which is more favorable than that resulting when treatment is initiated after symptoms appear. In practice, this requirement is met for a surprisingly small number of diseases. Early detection components of "health packages" must be developed, therefore, strictly on the basis of proven effectiveness. Existing programs should be revised in accordance with international guidelines, and adapted as needed to the local incidence and prevalence of disease and anticipated population compliance, so that the maximum benefit of early detection can be realized and the numerous hazards of screening avoided. PMID- 1607279 TI - High-dose chemotherapy: therapeutic potential in the age of growth factor support. AB - The steep dose-response curve for most chemotherapeutic drugs and the need to overcome tumor resistance has resulted in renewed interest in the use of high dose chemotherapy. Bone marrow rescue has allowed the dose-limiting barrier of hematopoietic suspension to be overcome. However, despite such salvage methods and the use of blood products and effective antibiotics, myelosuppression remains a major obstacle to treatment. The use of recombinant colony-stimulating factors in combination with bone marrow following high-dose chemotherapy may well shorten the period of neutropenia and reduce the frequency of neutropenia-related complications, thus making high-dose treatment more acceptable. PMID- 1607281 TI - Successful treatment with recombinant alpha 2 beta interferon for refractory idiopathic thrombocytopenic purpura. PMID- 1607282 TI - High-tech care and medical devices: the Safe Medical Devices Act of 1990. PMID- 1607283 TI - The community health nurse as advocate. PMID- 1607284 TI - Home care nursing orientation model. Justification and structure. AB - An orientation program for new nurses in a home care agency can be an effective tool that increases job satisfaction, alleviates a potentially high employee attrition rate, boosts morale, and thereby improves overall quality of patient care. PMID- 1607285 TI - Caseload management. A model for agencies and staff nurses. AB - With the theory behind case load management, home healthcare nurses are more likely to apply the theory to the management of their practice, instead of being treated like automatons that must provide 5 to 6 units of service every day to be productive, effective, and efficient. PMID- 1607286 TI - Outcome measurement from the functional status perspective. PMID- 1607287 TI - Home visiting for a posthysterectomy population. AB - There are many valid indications for providing home visits to posthysterectomy clients. In-home assessment of the client's status permits immediate care or referrals and saves unnecessary acute care visits to emergency rooms and physicians' offices. Nursing interventions have identified holistic healthcare needs and prevented other problems from developing. Assisting the clients in developing their problem-solving abilities enhances the goal of return to self care during the immediate postoperative follow-up and afterward. Finally, the vital role the clinical nurse specialists can play in the healthcare system is more clearly established for these consumers of care. PMID- 1607288 TI - Is home nursing for you? PMID- 1607290 TI - Place of death: home or hospital. PMID- 1607289 TI - The effect of time and temperature on blood glucose measurements. AB - Diabetic patients admitted for home healthcare services may require daily blood glucose measurements by the nurse until glucose control is achieved. Improper storage of blood specimens and unstable environmental temperature may alter the reliability of blood glucose measurements. Because accurate measurements are essential in decision making for diabetic control, specimen collection and handling are important concerns for home healthcare nurses. PMID- 1607291 TI - Buying time. PMID- 1607292 TI - Outcomes of care from patients' perspectives. PMID- 1607293 TI - Granny dumping: a case of caregiver stress or a problem relative? PMID- 1607294 TI - A nursing presence. PMID- 1607295 TI - Marilyn D. Harris, RN, MSN, CNAA, FAAN. PMID- 1607296 TI - Confocal microscopical analysis of epithelial cell heterogeneity in mouse Peyer's patches. AB - Cyanine dye fluorescence and alkaline phosphatase activities have been compared directly by confocal microscopy in a wide variety of cells present in the follicle-associated epithelium of the mouse Peyer's patch to test the hypothesis that antigen-transporting M cells have a low membrane potential. In order to make these comparisons it was first necessary to equilibrate living tissue with the membrane potential sensitive dye DIOC5(3), fix with glutaraldehyde and then incubate the fixed tissue with naphthol AS-BI phosphate, a substrate which is hydrolysed by alkaline phosphatase present in the luminal membrane of these epithelial cells. Naphthol AS-BI produced by this reaction is then coupled to Fast Red TR diazonium salt at the site of hydrolysis. Selecting the 488 nm wavelength of the argon laser source then allows one to measure alkaline phosphatase activities as Fast Red absorbance and membrane potentials by DIOC5(3) fluorescence. Results obtained show a linear correlation between membrane potential and alkaline phosphatase activity. Relative lack of alkaline phosphatase activity, determined in fixed tissue, has been used previously to identify antigen-transporting M cells (Smith et al., 1987). The present work shows that it is now possible to recognize these cells in living tissue by measurement of DIOC5(3) fluorescence. The possible importance of this finding in providing a way to study cell surface-antigen interactions taking place in living tissue is discussed. PMID- 1607297 TI - Histamine immunohistochemistry: a new and highly sensitive method for studying cutaneous mast cells. AB - Mast cells have characteristic granulae containing various glucoseaminoglycans, proteases and amines (predominantly histamine). The conventional histological methods for studying mast cells are based upon acidic ortho- and metachromatic routine stains of the glucoseaminoglycans. However, the success of these procedures is dependent upon both the fixatives and the tissues used. In this study, we wanted to find out whether an immunohistochemical procedure could overcome some of these difficulties. Normal human skin was fixed in five different types of fixative and processed for indirect immunofluorescence, using an antiserum to histamine. Only one, 4% carbodiimide in 0.1 M phosphate buffer (pH 7.4), resulted in immunostaining. The quality of the staining was good, with a high signal-to-noise ratio, and was located on the mast cells. The method made it possible to visualize small structures such as a single secreted granula, the thin cytoplasmatic extension of some cells, and a previously undescribed dendritic morphology of some of the mast cells. We therefore recommend this procedure for cellular studies of mast cells when accuracy is needed. PMID- 1607299 TI - Attachment to killing. PMID- 1607298 TI - Treating the hospitalized borderline patient: reworking trauma of toddlerhood. AB - Frequently borderline patients are found to have suffered specific traumata during the separation-individuation phase. These traumata seem to have been experienced by them as punishment for their attempts at autonomy or for their early masturbatory explorations. Psychoanalytically oriented hospital-based treatment can allow for reexperiencing and resolving these difficulties, as illustrated in a case presentation. PMID- 1607300 TI - Freud and the theatre. AB - Theatre historians credit Freud and his theories for being the prime impetus for the birth of the modern theatre. Freud's theatre-going activities varied throughout his life. In his younger days, he seemed to enjoy attending performances. In later life, he rarely went to the theatre except for an occasional Mozart opera or Shakespeare play. When writing about the drama, he tended to deal with it as a literary product rather than as a performed event. On only one occasion did he communicate to a friend that the healing cathartic effect of art might be greatest when viewing the drama. Although credited with being the "father" of the modern theatre, Freud was somewhat skeptical about its artistic merits and was certainly concerned about its emphasis on the irrational. However reluctant Freud was about modern dramaturgy, his ideas had a profound effect on playwrights, such as Schnitzler and O'Neill, and through them was instrumental in freeing the theatre from its Victorian moral straitjacket. Freud's ideas also served as the background for other psychoanalysts interested in the theatre, especially Otto Fenichel, who wrote the seminal paper on the actor's personality. PMID- 1607301 TI - Analytic time. AB - "Analytic time" refers to the unique qualities of the patient's experience of time in the context of treatment. Transference regression revives earlier developmental levels of temporal awareness, especially its intimate connections with separation experiences within the symbiotic dyad. Analytic time also alludes to the clinical observation that significant childhood events, such as the birth of a sibling, sometimes come to the fore when the "age" of the analysis matches the child's age when the event took place. Analytic time refers as well to other temporal aspects of treatment, onto which unconscious conflicts and fantasies can be displaced. The temporal structure of each session can evoke the same associations as does the temporal structure of the entire analysis. Recognition of the various possible meanings of the time structure of treatment may play a useful role in formulating reconstructions. Analytic time is one important component of the analytic frame. As such, its importance can easily be overlooked when the analyst becomes preoccupied with content, and ignores the more silent aspects of treatment. PMID- 1607302 TI - The death instinct revisited. PMID- 1607303 TI - Reflections on a child analysis with Anna Freud and an adult analysis with Ernst Kris. PMID- 1607305 TI - Categorization: a fundamental of unconscious mental activity. AB - Association formation and categorization, phenomena below volition and awareness, are in the unconscious domain. They reflect automatic processes of brain circuitry. The formation and maintenance of associations and categories require as well as yield neural energy, energy arising from cerebral metabolic processes. Automatic categorization is a fundamental element in perceptual, motoric, and cognitive functions as emphasized by Edelman (1987) who, further, relates categorization to dynamic cerebral cortical fields and to limbic fields for the necessary affective component. PMID- 1607304 TI - Associations between sexual experiences and fantasies in a nonpatient population: a preliminary study. AB - We have been interested in devising some methodology short of psychoanalytic therapy to study the relationship of conscious fantasy to personality trends and behavior. Presented here is a pilot study, utilizing the questionnaire technique, the sample consisting of 193 students enrolled at one prestigious urban university, that reports on the prevalence and content of conscious sexual fantasies in a normal (nonpatient) population and their relationship to sexual behaviors. Factor analysis suggested four experience and four fantasy clusters. Those individuals who score high on one experience factor are apt to score high on all other experience factors as well. The same is true of the fantasy factors. Our findings indicate that low sexual activity and low levels of sexual fantasy go together, whereas more sexual experience is connected to a greater range of sexual fantasy. Consequently, erotic fantasies cannot be viewed as compensation for lack of sexual outlet. Instead, there is a positive correlation between the two domains of sexual fantasies and sexual behaviors. Our overall results lead us to conclude that by and large, people are sexual generalists not specialists. PMID- 1607306 TI - Aloneness and the Isakower phenomenon. AB - Under the sway of the oedipal imperative, the Isakower phenomenon has long been regarded as a regressive perceptual defense against castration anxiety accompanying incestuous wishes, often stimulated by primal scene exposure fantasy. Clinical material from the psychoanalytic psychotherapy of a borderline patient with object constancy deficits is offered to support a reconceptualization of the Isakower phenomenon: Following annihilatory rage and the destruction of extant inner objects, resulting in a regression to the "drive organization of memory," the face-breast imagery within the Isakower phenomenon arrives as a hallucinatory alternative to unbearable aloneness. PMID- 1607307 TI - Treatment of dermatophytosis in cats. PMID- 1607308 TI - Concerned about "4-D meat". PMID- 1607309 TI - Why producers don't use veterinarians. PMID- 1607311 TI - How can we become compassionate? PMID- 1607310 TI - 1990 report of the American Association of Poison Control Centers: poisonings in animals. PMID- 1607312 TI - Diagnosis of luteal and follicular ovarian cysts by palpation per rectum and linear-array ultrasonography in dairy cows. AB - The purpose of this study was to determine and compare the accuracy of palpation per rectum and linear-array ultrasonography for diagnosing follicular vs luteal ovarian cysts in cows. Forty-seven examinations of ovarian cysts from 28 cows were diagnosed by palpation per rectum as either a firm, thick-walled structure (luteal cyst) or a soft, thin-walled structure (follicular cyst) during weekly herd examinations. The ovaries of each cow were then examined by ultrasonography. Ultrasonograms of cysts greater than 25 mm in diameter were diagnosed as luteal or follicular cysts and were recorded on videotape for evaluation by a second clinician. Serum progesterone concentrations at the time of examination were determined by radioimmunoassay and used to classify luteal (greater than 0.5 ng/ml) or follicular (less than or equal to 0.5 ng/ml) cysts. Selection of this discriminatory level was based on response of a proportion of cows with luteal cysts that were given 25 mg of prostaglandin F2 alpha at the time of diagnosis by ultrasonography. Sensitivity and specificity of palpation per rectum for diagnosis of type of ovarian cyst were low (43.3 and 64.7%, respectively). In contrast, sensitivity and specificity of ultrasonography were considerably higher (86.7 and 82.3%, respectively). Agreement between the 2 methods of diagnosis was 57.4%. Overall agreement between the 2 clinicians' diagnoses by ultrasonography was 85.1%. On the basis of our findings, we confirm that luteal and follicular cysts cannot be accurately differentiated by palpation per rectum alone. These data suggest that linear-array ultrasonography is more effective than palpation per rectum for diagnosing type of ovarian cyst in cows. PMID- 1607313 TI - Hematologic effects and feeding performance in cattle fed cull domestic onions (Allium cepa). AB - For 119 days, 36 cattle, allotted to 6 treatment groups, were fed a balanced growth diet containing 0, 5, 10, 15, 20, or 25% cull onions on a dry-matter basis. Cattle performance was comparable to that associated with barley-base non onion diet; statistical differences were not observed among treatments. During the first 28 days of the study, reduction in numbers of RBC, hemoglobin concentration, and PCV was observed in all cattle fed onions, but clinical anemia was not seen in any individual animal. After onion feeding was discontinued at 119 days, RBC numbers, hemoglobin concentration, and PCV returned to baseline values within 30 days. Heinz bodies were detected in erythrocytes of all cattle fed onions, and the percentage was proportional to the amount of onions consumed. Addictive onion consumption was prevented by mixing chopped or crushed onions in a total balanced ration. PMID- 1607314 TI - Morphometric evaluation of growth in llamas (Lama glama) from birth to maturity. AB - Normal growth characteristics of llamas (Lama glama) were evaluated from conception until 1 week after parturition in pregnant females (study 1) and from 1 month after birth to maturity (study 2). In study 1, pregnant multiparous llamas (n = 10) were measured at monthly intervals from conception until 1 week after parturition; in study 2, llamas (n = 270) were measured once. Body weight of pregnant llamas (study 1) did not increase significantly until after the eighth month of pregnancy. Llamas of study 2 reached mature height, length, thoracic circumference, and weight at 18, 24, 36, and 36 months of age, respectively. From 1 month of age to maturity, the growth characteristics of males, nonpregnant females, and females during the first 8 months of pregnancy did not differ. Correlations (r2) between height, length, and thoracic circumference related to body weight for all but the pregnant llamas during the last 3 months of pregnancy were 0.822, 0.834, and 0.948, respectively. The equation describing thoracic circumference as a predictor of body weight was: Weight (kg) = (1.005 x 10(-3)) x circumference (cm)2.424. PMID- 1607315 TI - Prolonged proestrus in a bitch with X chromosomal monosomy (77,XO). AB - A stunted Miniature American Eskimo bitch that had signs of proestrus, which persisted for almost 8 months, had a 77,XO karyotype. Despite signs of proestrus, the ovaries were small and fibrous, and there was no evidence of ovarian follicle development or corpora lutea. Except for its juvenile appearance, the rest of the reproductive tract was grossly normal. Clinical signs in this bitch were similar to those in human beings with Turner's syndrome. PMID- 1607316 TI - Subcutaneous emphysema from an axillary wound that resulted in pneumomediastinum and bilateral pneumothorax in a horse. AB - A 5-year-old Thoroughbred gelding was examined because of a small axillary wound sustained 5 days earlier and had resulted in extensive subcutaneous emphysema. Three days after admission, the horse's respiratory rate had increased to 72 breaths/min, and the horse appeared anxious and distressed. Thoracic radiography revealed pneumomediastinum and severe bilateral pneumothorax. Tube thoracostomy was performed on both hemithoraxes. The drains were connected to one-way suction valves and suction devices to decompress the thorax. A nasopharyngeal catheter was inserted, and oxygen insufflation was started. Cross ties were placed on the horse to limit movement, and the wound was packed. The horse improved within 30 minutes after initiating treatment. The horse was released 15 days after the development of pneumothorax, at which time the pneumothorax had resolved, the wound was no longer open, and the subcutaneous emphysema had greatly decreased. Although subcutaneous emphysema is usually regarded as a temporary cosmetic disfigurement, it can lead to serious complications such as pneumothorax. This case demonstrates that subcutaneous emphysema can lead to a life-threatening pneumothorax if the pressure is great enough to migrate through the mediastinum and into the pleural cavity. Horses with subcutaneous emphysema should be kept in confinement and monitored for the development of pneumothorax. PMID- 1607317 TI - Postpartum partial cystectomy through the vagina in a mare with everted partially necrotic bladder. AB - The bladder of a 750-kg Clydesdale mare had everted through the urethra into the vagina immediately after parturition. The bladder was reinverted into the peritoneal cavity by an attending veterinarian, but 4 days later, the bladder was everted again in the vagina. The mare was able to void urine through both ureters, which could be seen in the mucosal surface of the bladder. The everted bladder had become edematous and could not be reinverted through the urethra. A considerable portion of the fundus was necrotic. The mare was administered xylazine epidurally to induce perineal analgesia, and the necrotic portion of the bladder was resected and healthy bladder tissue was opposed with a double layer of simple continuous sutures. The urethral sphincter was longitudinally incised through the vaginal mucosa to allow reinversion of the bladder through the urethra. A purse-string suture inserted in the urethral opening decreased the urethral diameter and prevented recurrence of the condition. An inflated Foley catheter was maintained in the bladder for 5 days. The mare recovered normal urination after the catheter was removed. PMID- 1607318 TI - Hypovolemic hyponatremia and signs of neurologic disease associated with diarrhea in a foal. AB - Hypovolemic hyponatremia attributable to severe fluid and electrolyte alterations was diagnosed in a foal with diarrhea. Subsequent consumption of water resulted in rapid reduction of serum sodium concentration and serum osmolar depression. Clinical signs of neurologic disease developed including blindness, loss of menace response, and seizures. Treatment of this condition with IV administered fluids included hypertonic saline solution (7.2%; 2 ml/kg of body weight), and frequent monitoring of serum electrolyte concentrations and osmolality resulted in gradual correction of the fluid and electrolyte imbalance and resolution of the neurologic signs. Hyponatremia has been recognized in foals with renal failure, ruptured urinary bladder, and iatrogenic water overload. The key to diagnosis and management of profound hyponatremia is accurate diagnosis of the status of plasma volume and association of the electrolyte imbalance with clinical signs of neurologic disease. This report describes an unusual complication of a commonly encountered problem in equine practice and documents that the severe metabolic and electrolyte abnormalities associated with diarrhea can result in clinical neurologic disease. The differential diagnosis also should include bacterial sepsis, parasitism, thoracic mass, acute renal failure, congenital neurologic deficit, or seizure syndrome. Serum electrolyte disorders should be considered as a potential cause of signs of neurologic disease in foals with diarrhea. PMID- 1607319 TI - Pyloric adenocarcinoma in a ferret. AB - Pyloric adenocarcinoma was diagnosed in a ferret with clinical signs of gastric distention. The development of this tumor may be related to Helicobacter mustelae infection in the gastric mucosa of ferrets. Pyloric adenocarcinoma has only recently been reported in ferrets and should be considered as a differential diagnosis for gastric distention in this species. PMID- 1607320 TI - Epidemiologic features of von Willebrand's disease in Doberman pinschers, Scottish terriers, and Shetland sheepdogs: 260 cases (1984-1988) AB - During a study period from 1985 through 1988, plasma von Willebrand's factor antigen (vWF:Ag) concentration was measured as a marker for prevalence of the von Willebrand's disease (vWD) trait in Doberman Pinschers (doberman, n = 5,554), Scottish Terriers (scottie, n = 1,363), and Shetland Sheepdogs (sheltie, n = 4,279). Significant increase in prevalence of the trait was seen in scotties and shelties during this period. In 1988, 73% of dobermans, 30% of scotties, and 28% of shelties tested had abnormal vWF:Ag concentration (less than 50% vWF:Ag). We found significant differences between breeds with respect to age and vWF:Ag concentration of clinically affected dogs at time of diagnosis. The affected dobermans were older (doberman mean age, 4.6 years; scottie mean age, 1.7 years; sheltie mean age, 1.9 years) and had higher concentration of plasma vWF:Ag (doberman mean vWF:Ag, 15%; scottie mean vWF:Ag, 0%; sheltie mean vWF:Ag, 8%). Bleeding in affected dogs of all 3 breeds was observed predominantly from mucosal surfaces and from cutaneous sites of surgery or trauma. The most common site of mucosal bleeding in scotties and shelties was oral or nasal cavity, and in dobermans was the urogenital tract. Differences in clinical manifestations of vWD in purebred dogs may reflect heterogeneous defects within the vWF gene, causing a variety of abnormalities in production, structure, and function of vWF protein. Analogous to vWD in human beings, acquired deficiencies of vWF may also contribute to the clinical variability of vWD in dogs. PMID- 1607321 TI - Long-term effects of desmotomy of the accessory ligament of the deep digital flexor muscle in standardbreds: 23 cases (1979-1989). AB - Desmotomy of the accessory ligament of the deep digital flexor muscle (inferior check desmotomy) permitted Standardbred foals affected with flexural deformities to reach their full athletic potential. Long-term effects of inferior check desmotomy were examined in 23 Standardbreds over a 10-year period. Six of 11 foals that were treated surgically either raced 6 times and obtained a race record or were training sound (if yearlings). All 12 horses with flexural deformity that did not receive an inferior check desmotomy had an unfavorable outcome (no race record). Foals that had surgery performed at a younger age apparently had a better chance of racing or training sound because no foals treated surgically after 8 months of age had a favorable outcome and only 1 foal that was older than 5 months at the time of surgery had a favorable outcome. In 5 foals that had surgery with an unsuccessful outcome, 3 were greater than or equal to 1 year old at the time of surgery and were lame when training was started on the limb(s) with the desmotomy. PMID- 1607322 TI - Rabies in horses: 21 cases (1970-1990). AB - The records of 21 horses with rabies were reviewed. Results of fluorescent antibody testing for rabies antigen in brain tissue were positive in each case. According to the histories, 5 of the horses had been vaccinated for rabies between 4 to 24 months prior to the onset of the clinical signs. Bite wounds were not observed on any of the horses, and exposure to a suspected rabid animal was witnessed in only 5 cases. Clinical signs of disease at the time of initial examination included ataxia and paresis of the hindquarters (9/21, 43%), lameness (5/21, 24%), recumbency (3/21, 14%), pharyngeal paralysis (2/21, 10%), and colic (2/21, 10%). The major clinical signs observed over the course of hospitalization included recumbency (21/21; 100%), hyperesthesia (17/21; 81%), loss of tail and anal sphincter tone (12/21; 57%), fever (11/21; 52%), and ataxia and paresis of the hindquarters (11/21; 52%). Mean survival time after the onset of clinical signs was 4.47 days (range, 1 to 7 days). Supportive treatment, given to 9 horses, had no effect on survival time and did not correlate with the detection of negri bodies at necropsy. Cerebrospinal fluid (CSF) was obtained from 6 horses and was determined to be abnormal in 5. The most common abnormality was a slightly high total cell count (5/6), with a predominance of lymphocytes (4/6). The CSF total protein concentration was high in only 2 horses. At necropsy, there was gross evidence of diffuse brain edema, meningeal congestion, and focal areas of hemorrhage in 5 horses (24%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607323 TI - What is your diagnosis? Bilateral Salter-Harris type-II fractures of the medial epicondylar physis of each humerus. PMID- 1607324 TI - Quinolones for the treatment of brucellosis. PMID- 1607325 TI - Anti-endotoxin therapy and the management of sepsis. PMID- 1607326 TI - Effect of methotrexate on the germination and growth of Aspergillus fumigatus and Aspergillus flavus strains. AB - Methotrexate at concentrations of greater than or equal to 10(-5) M caused a significant reduction in the rate of germ tube formation of spores of Aspergillus fumigatus, but not of Aspergillus flavus, after 7 h incubation. At 10(-3) M the drug caused a significant reduction in germ tube elongation of A. fumigatus and A. flavus strains during the first 7 h of germination. After 18 h incubation, drug concentrations of greater than or equal to 4 x 10(-4) M produced greater than 80% reduction in growth of all strains tested. Potentiation of the antifungal effect against A. fumigatus was detected in tests in which methotrexate at 10(-4) M was used in combination with amphotericin B at 5 x 10( 7) M. PMID- 1607327 TI - In-vitro antimicrobial susceptibility of Rhodococcus equi. AB - Rhodococcus equi is an intracellular facultative, Gram-positive cocco-bacillary organism of increasing importance as a pulmonary pathogen in HIV-positive patients. This study was carried out to evaluate the optimal antibiotic combinations for treating such infections. Four human R. equi isolates and one reference strain were tested for their susceptibilities to 36 antibiotics. In vitro the most active antibiotics were amikacin, gentamicin, netilmicin, erythromycin, clarithromycin, roxithromycin, ciprofloxacin, sparfloxacin, rifampicin, vancomycin, teicoplanin, doxycycline, minocycline, imipenem, meropenem and trimethoprim/sulphamethoxazole. The only bactericidal antibiotics were the aminoglycosides, ciprofloxacin, sparfloxacin and vancomycin. As determined by FIC indices, four combinations were synergistic: rifampicin erythromycin, rifampicin-minocycline, erythromycin-minocycline and imipenem amikacin. However, no antibiotic combinations were synergistic with the time-kill kinetic method at achievable serum concentrations or at ten-fold and half-fold the MICs. Frequencies of selection of antibiotic-resistant mutants determined at concentrations of five- and ten-fold the MICs ranged from less than 1 x 10(-8) for erythromycin and trimethoprim/sulphamethoxazole to 5 x 10(-4) for amikacin. These results may be of help in selecting the antibiotics for treating infected HIV-positive patients. PMID- 1607328 TI - High-level resistance to gentamicin in Enterococcus faecium. AB - During a six-month period in a hospital in Ireland, four patients were infected (isolation from blood cultures) and two were colonized (isolation from rectal swabs) with strains of Enterococcus faecium highly resistant to gentamicin. MICs of gentamicin were greater than 1000 mg/L for all six strains, and each possessed a plasmid of approximately 50 MDa. Resistance to gentamicin was transferable by conjugation from two of the six strains, and was associated with transfer of the 50 MDa plasmid. This plasmid hybridized with a DNA probe specific for the bifunctional AAC(6')-APH(2") aminoglycoside-modifying enzyme. The mechanism of high-level gentamicin resistance in these strains appeared therefore, to be identical to that encountered in Enterococcus faecalis strains worldwide and reported in E. faecium strains in the USA. PMID- 1607329 TI - Prevalence of a plasmid-mediated type II dihydrofolate reductase gene among trimethoprim-resistant urinary pathogens in Greek hospitals. AB - The genetic basis of trimethoprim resistance was examined in 24 Klebsiella pneumoniae, 27 Enterobacter cloacae, five Enterobacter aerogenes and nine Serratia marcescens urinary isolates from five hospitals in Greece. Analysis of the 65 isolates by serotyping and phage-typing identified 53 distinct strains. Thirty-eight isolates (15 K. pneumoniae, 19 E. cloacae, two E. aerogenes and two S. marcescens) hybridized with a probe specific for a gene encoding type II dihydrofolate reductase (DHFR). Three of the K. pneumoniae and four of the E. cloacae isolates which reacted with this probe also hybridized with probes specific for type I DHFR and transposon Tn7. Two E. cloacae isolates hybridized only with the probe for type I DHFR, while a further three isolates hybridized only with the type I DHFR and Tn7 probes. None of the isolates hybridized with a probe for type V DHFR. The plasmids in transconjugants derived from 40 isolates were analysed by digestion with restriction enzymes and Southern blotting. Eighteen (45%) of the donors (12 K. pneumoniae and 6 E. cloacae) produced transconjugants containing plasmids of about 95 kb in size, while transconjugants from the other donors had plasmids in the range 100-185 kb. Of the 18 transconjugants containing a 95 kb plasmid, 15 had similar restriction endonuclease digest patterns, although they varied in terms of the range of antimicrobial resistances which they encoded. When EcoRI digests of these 15 plasmids were hybridized with the type II DHFR probe, a 23 kb common band reacted with the probe.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607330 TI - The incidence of antibiotic resistance in aerobic faecal flora in south India. AB - During a field study in South India in 1989, faecal specimens were collected from residents in villages and the town of Vellore in South India. Examination of the faecal specimens revealed that virtually the whole population carried commensal bacteria resistant to trimethoprim, ampicillin and chloramphenicol. Most specimens contained more than one type of bacterium resistant to each antibiotic. There was less resistance to nalidixic acid, with a higher proportion in the town (33%) than in the villages (13%). Although there was little cross-resistance of the ampicillin-resistant strains to later generation cephalosporins, 50% were resistant to the combination of amoxycillin and clavulanic acid. There was no significant cross-resistance of the nalidixic acid-resistant strains to fluorinated 4-quinolones, despite the free availability of ciprofloxacin and norfloxacin in the area. The probable reason for the high incidence of resistance to first generation antimicrobials is the extensive use of these agents, coupled with continuous exposure to large numbers of faecal micro-organisms. PMID- 1607331 TI - Comparison of gentamicin dosing regimens using an in-vitro model. AB - An in-vitro model which simulates in-vivo pharmacokinetics was used to compare the efficacy against Pseudomonas aeruginosa of dosing regimens of gentamicin which achieve different peak/trough concentrations but use the same total dose over 24 h. First exposure to gentamicin produced a rapid bactericidal effect which was proportional to the initial peak concentration. Subsequent doses of gentamicin produced a smaller bactericidal effect. Regrowth occurred with all dosing regimens, even after very high initial concentrations (26 mg/L). The time to reach bacterial counts above starting values was prolonged in relation to peak concentrations. Regrowth was also demonstrated in continuous infusion experiments which maintained very high concentrations (26 mg/L), although an inhibitory effect was evident compared with single dose experiments and the experiments mimicking in-vitro pharmacokinetics. There was little evidence of a post antibiotic effect. The data supports the use of larger initial and longer interval bolus dosing compared with current recommendations. PMID- 1607332 TI - Susceptibility of Treponema pallidum and other selected spirochaetes to zidovudine. AB - The antiviral nucleoside derivative zidovudine (3'-azido-3'-deoxythymidine) previously has been shown to be an effective antibacterial agent in animals infected with Escherichia coli or Salmonella typhimurium. Since HIV infection can alter the course of human syphilis with serious consequences, it was of interest to determine if the noncultivable spirochaetal agent of syphilis, Treponema pallidum, is susceptible to this compound. The progression of experimental rabbit syphilis over a three week period was unchanged in animals receiving either 50 or 150 mg/kg oral zidovudine daily. In addition, a number of cultivable pathogenic and nonpathogenic spirochaetes were tested for susceptibility to zidovudine in vitro. At a concentration of 100 mg/L, zidovudine had no detectable effect on spirochaete growth, morphology, or motility. Thus it appears that spirochaetes are generally not susceptible to this compound, and that long-term zidovudine therapy will not be of benefit in preventing or controlling syphilis or other spirochaetoses in HIV-infected humans receiving this drug. PMID- 1607333 TI - Determination of MICs by the E test. PMID- 1607334 TI - In-vitro and in-vivo activities of beta-lactam antibiotics on Yersinia enterocolitica. PMID- 1607335 TI - Necessity of a loading dose when using vancomycin in critically ill patients. PMID- 1607336 TI - Ototoxicity associated with a once daily dose amikacin regimen in febrile neutropenic patients. PMID- 1607337 TI - Proposed cefepime interpretive criteria for in-vitro susceptibility tests with Neisseria gonorrhoeae. PMID- 1607338 TI - In-vitro activity of twelve antibiotics against clinical isolates of Bilophila wadsworthia. PMID- 1607339 TI - Alternative antimicrobial agents to contemporary treatment of infections caused by Corynebacterium parvum (Propionibacterium acnes) PMID- 1607340 TI - An evaluation of the penetration of cefepime into prostate tissue in patients undergoing elective prostatectomy. PMID- 1607341 TI - The role of hemonectin in the cell adhesion mechanisms of bone marrow. PMID- 1607342 TI - A comparison between the Rappaport Classification and Working Formulation in cooperative group trials: the ECOG experience. AB - The Working Formulation (WF) for the classification of non-Hodgkin's lymphomas was shown to be reproducible and clinically relevant in the original study. However, it has not yet been tested by an NCI-supported cooperative clinical oncology group. As a result, the Hematopathology Subcommittee of the Eastern Cooperative Oncology Group (ECOG) undertook a retrospective study to compare concordance and practical utility between the WF and the Rappaport Classification (RC). Data indicate that with appropriate modifications to minimize unclassifiable lymphomas, the WF can be effectively utilized in cooperative clinical oncology groups. PMID- 1607343 TI - Specificity of heme for hemopoietic recovery from AZT toxicity. AB - The toxicity of azidothymidine (AZT) was studied on normal human bone marrow hemopoietic colony growth as determined by assays of CFU-E, BFU-E, and CFU-GM. The potential sparing effect of hemin and heme analogues on AZT-suppressed bone marrow was also investigated. AZT at a lower concentration (0.1 mumol/L) inhibited CFU-E by 68%, BFU-E by 84%, and CFU-GM by 59%. AZT at a higher concentration (1.0 mumol/L) inhibited CFU-E by 88%, BFU-E by 90%, and CFU-GM by 69%. Addition of hemin (10 mumol/L) to cultures containing AZT (0.1 mumol/L) increased CFU-E growth by 279%, BFU-E by 282%, and CFU-GM by 72%. A similar concentration of heme analogues did not have an enhancing effect; in contrast, zinc protoporphyrin (ZnPP) was inhibitory to bone marrow progenitors CFU-E, BFU E, and CFU-GM. In addition, no enhancement of colony growth was obtained when progenitor cells were cultured in the presence of 10(-2)-10(-5) M iron. These results demonstrate that exogenous hemin has a specific beneficial effect on human bone marrow hematopoietic progenitor cells which is not seen with iron or other metalloporphyrins. Furthermore, this beneficial effect includes a reversal of the cytotoxic effect of AZT on bone marrow progenitors. PMID- 1607344 TI - Apoptotic megakaryocyte dysplasia in the myelodysplastic syndromes. AB - The terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis to form compact, denuded megakaryocyte nuclei (DMK) surrounded by a thin rim of cytoplasm. Increased numbers of DMK have been reported in patients with acquired immune deficiency syndrome (AIDS) and chronic myeloproliferative disorders. In this study the bone marrow biopsies of 20 patients with various FAB subtypes of myelodysplastic syndrome (MDS) were examined for the presence of DMK cells and semiquantified for marrow reticulin level. For all MDS subtypes, a 9% or greater incidence of DMK in the total megakaryocyte population of the bone marrow was associated with a significant deposit of reticulin in the marrow. Immunocytochemical staining for Factor VIII (Von Willebrand factor), showed the abnormal deposition of this megakaryocyte protein in the extravascular stroma around many of the DMK cells. These findings are consistent with a hypothesis for excess stromal reticulin based on the defective maturation and intramedullary death of large numbers of megakaryocytes. The number of DMK in the marrow biopsies of MDS patients may have prognostic significance. PMID- 1607345 TI - Burkitt cell leukemia with myelodysplasia as a presentation of HIV infection. AB - Hematologic manifestations of human immunodeficiency virus (HIV) infection include cytopenias, non-Hodgkin's lymphoma, and myelodysplasia. Acute lymphocytic leukemia has rarely been reported in association with HIV infection. We describe a patient who presented with Burkitt cell leukemia and myelodysplasia as her initial manifestation of HIV infection. The dysplastic features included circulating asymmetric binucleated red blood cells as well as pseudo Pelger-Huet cells. To the best of our knowledge, this has not been previously reported. PMID- 1607346 TI - Patents, biotechnology, and hematologic pathology. PMID- 1607347 TI - Psychopharmacological screening criteria. APA Committee on Research on Psychiatric Treatments. AB - This chapter includes a revision of psychopharmacological screening criteria originally developed in 1977-78 by the American Psychiatric Association (APA) and the National Institute of Mental Health (NIMH). This recent revision by the APA Committee on Research on Psychiatric Treatments provides criteria that are of considerable help in carrying out drug usage evaluations. Also included are useful suggestions for medical record documentation of specific classes of drugs, as well as for identification of adverse drug reactions. Thresholds for review are suggested. PMID- 1607348 TI - The effects of pregnancy on preexisting panic disorder. AB - BACKGROUND: Limited evidence suggests that pregnancy may be associated with a reduction of panic and related symptoms. The authors investigate reported changes in panic symptoms during pregnancy. METHOD: Questionnaires asking about changes in panic and phobic avoidance symptoms during pregnancy were mailed to 129 women who had previously participated in our Anxiety Disorders Program over a 5-year period; all had diagnoses of panic disorder by DSM-III-R criteria. Reported here are responses from 22 of the women who experienced pregnancy after the onset of panic disorder. RESULTS: A majority of women (14 of 22) reported a decrease in panic symptoms during pregnancy, but significant variability in this phenomenon occurs between and within individuals. CONCLUSION: A subpopulation of women may experience improvement in panic symptoms during pregnancy, which has implications for management of these patients. Further research is needed to verify the existence of such a subpopulation and to determine an etiology. PMID- 1607349 TI - Response to sleep deprivation in three women with postpartum psychosis. AB - BACKGROUND: Postpartum psychotic disorders are rare and poorly understood phenomena occurring after approximately 1 in 2000 births. Increasing attention has been given to the concept of postpartum psychosis as an affective spectrum disorder. We sought to characterize the responses to sleep deprivation of three women with postpartum psychotic and mood symptoms. METHOD: Three hospitalized postpartum women with no prior history of psychotic disorder were treated according to a partial sleep deprivation protocol. Each patient was awakened at 2:00 a.m. and kept awake until 9:00 p.m. the following night. A full and an abbreviated Hamilton Rating Scale for Depression (HAM-D) were completed for each patient before and after partial sleep deprivation. RESULTS: Two of the three patients became transiently manic and the third became hypomanic after sleep deprivation. HAM-D scores decreased drastically for each patient. After recovery sleep, each patient de-escalated but required further treatment with mood stabilizing agents. CONCLUSION: These findings suggest that postpartum psychosis in our patients may represent a variant of bipolar affective disorder. PMID- 1607350 TI - Catatonia associated with bupropion treatment. PMID- 1607351 TI - Single-dose fluoxetine in management of premenstrual syndrome. PMID- 1607352 TI - A case of baclofen-induced psychotic depression. PMID- 1607353 TI - Treatment of fluoxetine-induced anorgasmia with amantadine. PMID- 1607354 TI - Psychiatrists and physical illness: clarification. PMID- 1607355 TI - Crystallization and preliminary X-ray structure analysis of pigeon egg-white lysozyme. AB - Calcium binding lysozyme from pigeon egg-white was crystallized by the hanging drop vapor diffusion technique using ammonium sulphate as a precipitant. The crystals belong to the orthorhombic system, space group P2(1)2(1)2(1), and have unit cell dimensions of a = 34.2 A, b = 34.8 A, and c = 99.4 A. One asymmetric unit contains one molecule of the pigeon lysozyme. The crystals diffract X-rays at least to 2.0 A resolution and are suitable for high resolution structure analysis. The diffraction data up to 3.0 A resolution were collected with a diffraction image processor, DIP100, using a Fuji imaging plate as an area detector. The structure was solved by the molecular replacement technique and refined to an R factor of 0.216. Least-squares fitting of the main-chains of pigeon egg-white lysozyme with those of chicken egg-white lysozyme and baboon alpha-lactalbumin showed that the main-chain folding of pigeon lysozyme is more similar to that of chicken lysozyme than that of alpha-lactalbumin. The largest differences between the pigeon and chicken lysozymes are in the surface loop regions. PMID- 1607356 TI - Determination of transcriptional activities of typical gene promoters in HL-60 cells. AB - We developed a highly sensitive procedure for assaying chloramphenicol acetyltransferase (CAT) enzyme activity in extracts of eukaryotic cells transfected with the CAT gene expression vector, by modification of the partition extraction procedure described by Sleigh [Anal. Biochem. 156, 251-256 (1986)]. The sensitivity of the new method was improved 100-fold on commercial purified enzyme. In routine measurements with cell extracts a CAT activity as low as 1.3 x 10(-4) unit could be measured within an error of less than 30%. The CAT enzyme expressions in undifferentiated human promyelocytic leukemic cell line HL-60 from typical gene promoters could be measured by the new method and compared to select a stronger promoter. Similar measurements were made with more mature monocytic THP-1 cells to evaluate the change in the promoter activity with cell maturation. Differentiation induction with 12-O-tetradecanoylphorbol-13-acetate (TPA) activated transcription from the human immunodeficiency virus (HIV) promoter about 10-fold in HL-60 cells, as expected, but the level was less than that in untreated THP-1 cells. In addition, a similar activation was observed in THP-1 cells as well. PMID- 1607357 TI - Amino acid sequence of sweet-taste-suppressing peptide (gurmarin) from the leaves of Gymnema sylvestre. AB - The complete amino acid sequence of a sweet-taste-suppressing peptide, gurmarin, from the leaves of Gymnema sylvestre was determined by the Edman analysis of peptides derived from digests obtained with Staphylococcus aureus V8 protease, pyroglutamyl aminopeptidase, and lysyl endopeptidase. Gurmarin consists of 35 amino acid residues with an amino-terminal pyroglutamyl residue and has the molecular weight of 4,209. Gurmarin has no significant homology with other known proteins. PMID- 1607358 TI - Human long-chain acyl-CoA synthetase: structure and chromosomal location. AB - A complementary DNA clone encoding the entire human long-chain acyl-CoA synthetase was isolated and the total 698-amino acid sequence was deduced. The amino acid sequence of human long-chain acyl-CoA synthetase shows 84.9% identity to that of rat long-chain acyl-CoA synthetase. The nucleotide sequences of the protein coding regions between human and rat long-chain acyl-CoA synthetase mRNAs are highly conserved (85.6%), whereas those of the 3' untranslated regions are less conserved (72%). The location of the human long-chain acyl-CoA synthetase gene was identified on chromosome 4 by spot hybridization of flow-sorted chromosomes. Computer-assisted homology search revealed a significant similarity of the enzyme with the enzymes of the luciferase family. Based on this similarity, the structure of human long-chain acyl-CoA synthetase can be divided into five domains: the N-terminus, two domains similar to those in enzymes of the luciferase family, a long gap region between the similar domains and the C terminus. PMID- 1607359 TI - Interaction of glycophorin with lipid bilayer studied by calorimetry, densitometry, static light scattering, and electron microscopy. AB - In the first part of the present work the interaction of glycophorin with dimyristoylphosphatidylcholine (DMPC) is studied by freeze fracture electron microscopy, densitometry, calorimetry, and 90 degree static light scattering. An exothermic lipid/protein interaction energy of WP = 190 kJ.mol-1 was found by application of the well known Van Laar relation for the displacement of the freezing point and the Gibbs-Duhem relationship. Secondly, the effects of Ca2+ on the lipid/protein interaction were studied. Following Ca2+ addition a remarkable decoupling of the interaction of the glycophorin head group with the bilayer surface was revealed by densitometry and gold-labeling electron microscopy. It is estimated that about 80% of lipid once disturbed by the adsorption of glycophorin head groups is decoupled after addition of Ca2+. Thirdly, the selective interaction of glycophorin with binary lipid mixtures was studied, including the mixtures of DMPC with dimyristoylphosphatidylserine (DMPS) and dilauroylphosphatidylcholine (DLPC), and the mixture of dipalmitoylphosphatidylcholine (DPPC) with DLPC. PMID- 1607360 TI - Induction of enzymes involved in fatty acid beta-oxidation in Pseudomonas fragi B 0771 cells grown in media supplemented with fatty acid. AB - Induction of the enzymes involved in fatty acid beta-oxidation in Pseudomonas fragi B-0771 cells grown in a medium containing straight chain saturated fatty acids was studied. The acyl-CoA dehydrogenase (ACDH) activity was induced during the exponential phase in cells grown in palmitic acid-supplemented medium, reached a maximum at the early stationary phase, and then gradually decreased thereafter. Changes in the overall activities of 2-enoyl-CoA hydratase and 3 hydroxyacyl-CoA dehydrogenase, both existing on the multienzyme complex (HDT) involved in fatty acid beta-oxidation, were similar to that in ACDH activity. Straight chain saturated fatty acids having more than 6 carbon atoms could induce both the ACDH and HDT activities, and C13-C15 fatty acids caused the greatest induction of both activities. Changes in the overall activities of 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase correlated with that in the amount of the alpha-subunit of HDT during the entire culture period in the medium containing palmitic acid. Surprisingly, the stoichiometry of the alpha- and beta subunit proteins of HDT was not maintained into the stationary phase culture, though the genes encoding the alpha- and beta-subunits are tandemly coded in bacterial genomic DNA. PMID- 1607361 TI - Dihydrofolate reductase gene as a versatile expression marker. AB - The Escherichia coli dihydrofolate reductase (DHFR) gene has been used as a genetic marker specifying trimethoprim resistance (TmpR). In order to use the DHFR gene as a versatile expression marker, we have constructed three types of plasmids: promoter cloning vector, terminator cloning vector, and the plasmid containing the DHFR gene cassette. In these systems, the selection of recombinant plasmids was carried out just by examining the TmpR phenotype of the transformed cells. Then, levels of the enzymatic activity of DHFR were measured to evaluate the efficiency of promoters and terminators in the fused DNA fragment. An expression plasmid which resulted in the E. coli host cells being able to produce DHFR up to 20% of total cellular proteins was also constructed by changing the promoter and Shine-Dalgarno sequences of the DHFR gene. PMID- 1607362 TI - Dihydrofolate reductase as a new "affinity handle". AB - Dihydrofolate reductase (DHFR) has been demonstrated to be a versatile "affinity handle" for expression of recombinant proteins. The DHFR "handle" has advantages not only in terms of efficiency of expressing the fusion protein as a soluble form but also in stabilizing unstable polypeptides and facilitating purification of the expressed protein by means of methotrexate-bound affinity chromatography and by making use of the enzyme activity. Fifteen genes encoding different lengths of polypeptides of 5 to 44 amino acids were chemically synthesized and introduced into expression vectors, pTP70-1 or its derivatives. All the polypeptide genes were efficiently expressed in Escherichia coli cells as fusion proteins which show DHFR activity. The respective fusion proteins were highly purified from cell-free extracts by monitoring the DHFR activity at each purification step. The use of methotrexate-bound affinity chromatography was very effective. In order to cut out the polypeptides, the purified fusion proteins were treated with either BrCN or site-specific protease according to the spacer sequence. The objective polypeptide was purified by means of a reversed-phase high-pressure liquid chromatography (HPLC) system. Specific cleavage of the purified fusion protein actually yielded very few peptide fragments, so the assignment and isolation of the objective polypeptide were carried out without difficulty. PMID- 1607363 TI - Studies on the active site of human alpha-amylases: examination of the third subsite S3' of the aglycone-binding site by control of substrate binding mode. AB - Modified maltooligosaccharides, IG-G-G-G-AG-G (IG: 6-deoxy-6-iodo-D-glucopyranose residue, G: D-glucopyranose residue, AG: 6-amino-6-deoxy-D-glucopyranose residue, -: alpha-1,4-glycosidic linkage), IG-G-G-G-AG-M (M: methyl), and IG-G-G-G-AG-phi (phi: phenyl) were prepared by the use of cyclodextrin glucanotransferase in order to examine the third subsite (S3') of the aglycone-binding site of human salivary and pancreatic alpha-amylases. Human alpha-amylases hydrolyzed the modified maltooligosaccharides to IG-G-G and G-AG-G, IG-G-G and G-AG-M, and IG-G G and G-AG-phi. This implied that G, M, and phi fit into S3'. There was no difference in the rate parameters between the two enzymes. The Km values for the hydrolysis of IG-G-G-G-AG-G by both enzymes were the same as those for IG-G-G-G AG-M, and twice those for IG-G-G-G-AG-phi. The results showed that S3' of the two enzymes has no affinity for the glucose residue and is not a subsite but a hydrophobic environment. PMID- 1607364 TI - Immunochemical detection of arachidonoyl-preferential phospholipase A2. AB - Monoclonal antibodies were raised against rabbit platelet cytosolic arachidonoyl preferential phospholipase A2. The antibodies precipitated the arachidonoyl preferential phospholipase A2 activity in the soluble fraction of a rabbit platelet lysate in combination with an immobilized anti-mouse immunoglobulin antibody, and reacted predominantly with a protein exhibiting a molecular weight of approximately 88,000 on immunoblotting analysis. All three antibodies established so far reacted with human platelet arachidonoyl-preferential phospholipase A2 as effectively as the rabbit platelet enzyme. One of them reacted with the rat platelet arachidonoyl-preferential enzyme, whereas none of them reacted with rabbit platelet secretory 14-kDa group II phospholipase A2. The existence of an immunologically related phospholipase A2 was further shown in rabbit granulocytes, brain, lung, and liver, rat and mouse mast cells, and human monocytoma U937 cells. Thus, an arachidonoyl-preferential phospholipase A2 with similar structural properties appeared to be expressed in a variety of cells and tissues. PMID- 1607365 TI - Characterization of rat liver mannan-binding protein gene. AB - We previously found that rat liver mannan-binding protein (L-MBP) is encoded by two species of mRNA of 1.4 and 3.5 kb long. In this study, the structure of the gene encoding rat L-MBP was determined from the sequences of isolated genomic DNA clones and PCR amplified DNA fragments. Rat L-MBP is encoded by at least three species of mRNA, the differences among which are generated by an alternative splicing at the 5'-nontranslated region and an alternative utilization of polyadenylation sites. The rat L-MBP gene consists of six exons separated by five introns. The coding region of rat L-MBP mRNA is encoded by four exons (Exons III VI), the 5'-noncoding region by Exons I and II, and the 3'-noncoding region by Exon VI. The exon-intron boundaries of L-MBP are completely identical to those of rat serum and human MBP, suggesting that all three MBPs are derived from a common ancestral gene. PMID- 1607366 TI - Primary structures of the genes, faoA and faoB, from Pseudomonas fragi B-0771 which encode the two subunits of the HDT multienzyme complex involved in fatty acid beta-oxidation. AB - Three enzyme activities involved in fatty acid beta-oxidation, i.e., those of enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-oxoacyl-CoA thiolase, are exhibited by one multienzyme complex (HDT) composed of two molecules each of two peptides in Pseudomonas fragi. Using specific antisera against the two subunits of HDT, we isolated the genes encoding the subunits of HDT and designated them "faoA" (for the alpha-subunit) and "faoB" (for the beta-subunit). Their complete nucleotide sequences were determined and it was revealed that faoA and faoB, both with individual putative S.D. sequences at suitable positions, formed a cluster, in that order. The amino acid sequences deduced from the nucleotide sequences of the two genes indicated that the alpha-subunit, encoded by faoA, is a polypeptide of 715 amino acid residues, and that the beta-subunit, encoded by faoB, consists of 390 amino acid residues lacking the first methionine of the primary product encoded by faoB. Immunoblotting of cell lysates prepared from Escherichia coli transformants carrying plasmids which possess the faoA and/or faoB gene with antisera against the subunits of HDT showed that both the faoA and faoB genes were transcribed and translated in E. coli. The overall activities of 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase were increased in the E. coli cells transformed with the plasmid possessing the faoA gene, suggesting that both the hydratase and dehydrogenase activities may be exhibited by the alpha-subunit of HDT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607367 TI - Autolytic transition of mu-calpain upon activation as resolved by antibodies distinguishing between the pre- and post-autolysis forms. AB - A novel method to observe the autolytic activation of a mammalian cytoplasmic calcium protease, mu-calpain, was developed using a set of antipeptidic antibodies capable of distinguishing between the pre- and post-autolysis forms of the enzyme. Antibodies raised against synthetic peptides designed to match the N terminal sequences of the pre- and post-autolysis forms of the mu-calpain large subunit reacted specifically with the corresponding form of calpain and not with the other. The antibodies were specific and sensitive enough to detect the antigens in crude cell lysates. The relevance of the immunochemical detection of calpain activation was confirmed by the observation that proteolysis of a substrate protein by purified mu-calpain paralleled autolysis at various pCa as probed by these antibodies and that autolysis preceded substrate proteolysis. We also observed calcium-dependent autolysis of calpain accompanying subsequent proteolysis of substrate in intact cells using the antibodies. The method will provide a novel approach to assess the physiological targets of the enzyme by determining the local intracellular sites of calpain activation. PMID- 1607368 TI - Alteration of the carbohydrate-binding specificity of the Bauhinia purpurea lectin through the preparation of a chimeric lectin. AB - A chimeric lectin gene was constructed by using a cDNA clone coding the Bauhinia purpurea lectin (BPA) in which a part of the metal-binding region was replaced by the corresponding region of the mannose-binding Lens culinaris lectin (LCA). The chimeric lectin expressed in Escherichia coli was found to bind alpha mannosyl bovine serum albumin (BSA) and this binding was inhibited by mannose. PMID- 1607369 TI - Transport of 1,5-anhydro-D-glucitol into human polymorphonuclear leukocytes. AB - 1,5-Anhydro-D-glucitol (AG) is one of the main polyols and its structure resembles glucose. It has been proposed that decreased serum AG concentrations in diabetic patients are a novel indicator of diabetic metabolic derangement. However, the pathway of AG metabolism still remains to be clarified. In this study we investigated the transport of AG into human polymorphonuclear leukocytes (PMNLs) isolated from healthy volunteers and found that 0.1 mM 3-O-methy-D glucose (3OMG) was equilibrated with a half saturation time of 10 s, while the uptake rate of AG was much slower. The concentration dependence of AG uptake revealed that the AG transport velocity reached a plateau, with a Km of about 50 mM and Vmax of about 25 nmol/min/10(7) cells. Transport of 14C-labeled 3OMG was inhibited by unlabeled D-glucose or AG in a dose-dependent manner. The mean inhibition constant (Ki) for D-glucose and for AG were 1.06 and 4.93 mM, respectively. Cytochalasin B (20 microM) inhibited 3OMG transport by 90% but AG transport by only 50%. S/V for 14C-labeled AG transport plotted against the concentration of unlabeled 3OMG showed a non-linear and biphasic pattern. These results suggest that AG influx into PMNLs is mediated not only by the cytochalasin B-sensitive glucose transport system but also via another facilitated transport system. PMID- 1607370 TI - Cytokine and growth factor production by monocytes/macrophages on protein preadsorbed polymers. AB - These studies evaluate the effect of biomedical polymers: Biomer, polydimethyl siloxane (PDMS), polyethylene, expanded polytetrafluoroethylene (ePTFE), Dacron, and the control polystyrene with or without adsorbed proteins IgG, fibrinogen, and fibronectin on the ability of activated human monocytes/macrophages to produce Interleukin 1 Beta (IL-1-B), Interleukin 6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-A). Monocytes/macrophages incubated on biomedical polymers with or without protein preadsorption produce variable levels of IL-1-B, IL-6, and TNF A dependent on the polymer and adsorbed protein. IL-6 was produced in the greatest quantity and was the most influenced by protein adsorption. ePTFE and PDMS polymers were least stimulating while polystyrene was the most stimulating of monocyte activity. Adsorbed IgG consistently altered the ability of the polymers to activate monocytes/macrophages to produce cytokines. These studies provide important insight into conditions which modulate monocyte/macrophage activity in response to protein preadsorbed biomedical polymers. PMID- 1607371 TI - Bone formation process in porous calcium carbonate and hydroxyapatite. AB - This study determined the bone formation in porous calcium carbonate (CC) and porous hydroxyapatite (HA) in ectopic sites. The bone formation stimulus was derived from bone marrow cells. CC and HA in the shape of disks were implanted with or without rat marrow cells into subcutaneous sites of syngeneic rats. The CC and HA had identical microstructure: pore size was 190-230 microns, porosity was 50-60% and they were fully interconnected. Bone did not form in any implants without marrow cells (disks themselves), whereas bone consistently formed in the pores of all implants with marrow cells after 4 weeks. The bone formation of both CC and HA occurred initially on surface of the pore regions and progressed toward the center of the pore. Scanning electron microscopy and electron-probe microanalysis revealed a continuum of calcium at the interfaces of both bone/CC and bone/HA implants. These results indicate that the bone formation in calcium carbonate derived from marine corals is comparable to the bioactive hydroxyapatite. PMID- 1607372 TI - Bone induction by demineralized bone particles: long-term observations of the implant-connective tissue interface. AB - Allogeneic demineralized bone (DB) powder was applied to subcutaneous pockets and cranial defects of rats and histological, histomorphometrical, and radiological evaluation was performed one to 52 weeks after implantation. In both type of implants cartilage formation was observed after 1 week between DB particles and in former vascular channels and cervices within the particles. Foci of bone formation were observed after 2 weeks in the center of the implant. Remineralization of DB particles only occurred in close contact with the new bone tissue by which they became incorporated, indicating that remineralization of DB is a continuation of a process which has started in live bone. At all times, the interface between implant and connective tissue of the host consisted of a layer of non-remineralized DB particles embedded in fibrous connective tissue. This rim was thinner at the dura-mater-side in the cranial implants, compared with the skin-side of the same implants as well as all sides of the subcutaneous implants. The rim became thinner with time but never disappeared completely. The outer contour of the mineralized implant sometimes ran right through a DB particle. A critical concentration of bone-inducing agent leaking from DB particles seems to be necessary for bone induction. We suggest that at the interface of the implant and loose connective tissue this concentration is never reached, which results in maintenance of the rim. PMID- 1607373 TI - Biocompatibility studies on plasma polymerized interface materials encompassing both hydrophobic and hydrophilic surfaces. AB - The biocompatibility of radiofrequency plasma polymerized films (less than 100 nm thick) deposited on biomedical polymer supports has been characterized by in vitro and in vivo methods. The polymer interface materials covered a wide range of elemental composition and surface properties, and were prepared from N-vinyl-2 pyrrolidone, gamma-butyrolactone, n-hexane, and hexamethyldisilazane (PPHMDSZ). The biocompatibility studies showed that the interface materials were noncytotoxic to mouse and human fibroblasts, as shown by morphologic evaluation, and by determination of extracellular LDH; and they did not stimulate interleukin 1-like production from human monocytes, as indicated by a thymocyte proliferation assay. The human fibroblast proliferation assay showed that three of the polymers supported cell growth at levels comparable to, or greater than, polymer controls, while the hydrophobic PPHMDSZ inhibited both cell attachment and proliferation. The response to subcutaneous implantation for all test materials was indicative of biocompatibility, with rapid resolution of the acute phase response and normal wound healing. The wide range of composition and surface properties for the plasma polymerized films evaluated in this study suggest that this general class of materials is likely to exhibit excellent biocompatibility. PMID- 1607374 TI - Adhesive bone cement containing hydroxyapatite particle as bone compatible filler. AB - Acrylic bone cement containing hydroxyapatite (HA) as a filler was developed using 4-methacryloyloxyethyl trimellitate anhydride (4-META) to promote adhesion both to bone and HA. The mechanical strengths of the cement did not decrease significantly with increasing HA in the cement by 4-META. However, strengths decreased with increasing HA content in the absence of 4-META. Scanning electron micrographic examination of fractured surfaces of the cement clearly showed that the HA particles adhered to the matrix resin when 4-META was added. Thus, it was important to maintain the original mechanical strengths for 4-META. The HA particles along the surface increased with increased HA content in the cement. The cement adhered to bone with a tensile bond strength was higher than 10 MPa. PMID- 1607375 TI - Thrombin and albumin adsorption to PVA and heparin-PVA hydrogels. I. Single protein isotherms. AB - More radiolabeled thrombin was adsorbed to heparin-polyvinyl alcohol (PVA) than to PVA, consistent with a specific interaction with the immobilized heparin. The maximum surface concentration on heparin-PVA was estimated to be approximately 450 nmol/m2 with an apparent affinity constant (Ka) of 2.5 microM-1; on PVA, the plateau concentration was 10 nmol/m2 with a Ka less than 1 nM-1. There was little difference in bovine serum albumin (BSA) adsorption between PVA and heparin-PVA. Interestingly, thrombin adsorption to polyethylene was indistinguishable from that to PVA despite the large difference in surface chemistry. BSA adsorbed to polyethylene with higher affinity than to the hydrogels, although the plateau concentrations were comparable. The adsorbed thrombin was biologically inactive at least towards chromogenic substrate, with the residual activity on PVA unaffected by subsequent incubations with antithrombin III. PVA and heparin-PVA presented a heterogeneous and complex substrate for interaction with proteins. The adsorbed protein was likely present in multiple states depending on the groups with which it interacted. PMID- 1607376 TI - Calcification and stress distribution in bovine pericardial heart valves. AB - There is a strong relationship between mechanical stress and calcification in biological prosthetic heart valves. A dynamic in vitro calcification test has been used to study the relationship between stress distributions in the leaflets of bovine pericardial valves and the deposition of calcium over the leaflet surfaces. Intuitive stress regions have been defined over the leaflet surfaces. Calcium uptake by the leaflets has been assayed directly by ashing of leaflet material and analysis of the ash by atomic absorption spectrophotometry. Calcium and phosphorus distribution over the leaflet surface has been analyzed using energy-dispersive x-ray analysis by scanning electron microscope and data points assigned to the appropriate stress region. The uptake of calcium is assessed by comparing stress regions, surfaces, and the degree of calcification of the valve. Differences between stress regions and surfaces are significant. Uptake of calcium in these valves appears to be strongly related to the degree and type of stress present in the valve leaflets. PMID- 1607377 TI - Agarose for a bioartificial pancreas. AB - Islets were encapsulated into 5% concentration agarose microbeads. The effect of microencapsulation on islet allograft survivals was determined using a streptozotocin-induced diabetic (STZ) mouse and a nonobese diabetic (NOD) mouse as recipients. All five STZ BALB/c mice receiving microencapsulated islets (C57BL/6) maintained normoglycemia indefinitely. When NOD mice were used as recipients of the bioartificial pancreas, four of five grafts (islets from C3H/He) functioned for more than 80 d. Two of five NOD mice maintained normoglycemia until animals were sacrificed at 102 and 192 postoperative d. Microbeads made of commercially available agarose can effectively prolong alloislets functioning in the STZ-diabetic mouse and even in the NOD mouse (animal model of human type I diabetes) without the use of any immunosuppressive drug. PMID- 1607378 TI - Examining the function and regulation of hsp 70 in cells subjected to metabolic stress. AB - Members of the heat-shock protein (hsp) 70 family, distributed within various cellular compartments, have been implicated in facilitating protein maturation events. In particular, related hsp 70 family members appear to bind nascent polypeptides which are in the course of synthesis and/or translocation into organelles. We previously reported that in normal, unstressed cells, cytosolic hsp 70 (hsp 72/73) interacted transiently with nascent polypeptides. We suspect that such interactions function to prevent or slow down the folding of the nascent polypeptide chain. Once synthesis is complete, and now with all of the information for folding present, the newly synthesized protein appears to commence along its folding pathway, accompanied by the ATP-dependent release of hsp 72/73. Herein, we examined how these events occur in cells subjected to different types of metabolic stress. In cells exposed to either an amino acid analog or sodium arsenite, two potent inducers of the stress response, newly synthesized proteins bind to but are not released from hsp 70. Under these conditions of metabolic stress, we suspect that the newly synthesized proteins are unable to commence proper folding and consequently remain bound to their hsp 70 chaperone. In cells subjected to heat shock, a large number of both newly synthesized as well as mature proteins are rendered insoluble. Within this insoluble material are appreciable amounts of hsp 72/73. Finally, we show that in cells depleted of ATP, the release of hsp 70 from maturing proteins is inhibited. Thus, in cells experiencing metabolic stress, newly synthesized proteins unable to properly fold, as will as mature proteins which begin to unfold become stably bound to hsp 72/73. As a consequence and over time, the free or available levels of pre-existing hsp 72/73 are reduced. We propose that this reduction in the available levels of hsp 72/73 is the trigger by which the stress response is initiated. PMID- 1607379 TI - Heat shock gene regulation by nascent polypeptides and denatured proteins: hsp70 as a potential autoregulatory factor. AB - Heat shock genes encode proteins (hsp's) that play important structural roles under normal circumstances and are essential to the cells' ability to survive environmental insults. Evidence is presented herein that transcriptional regulation of hsp gene expression is linked with the regulation of overall protein synthesis as well as with the accumulation of proteins denatured by stressful events. The factor that connects the three processes appears to be one of the hsp's, presumably a member(s) of the hsp70 family. Biochemical experiments demonstrate that complexes containing hsp70 and heat shock transcription factor, the specific regulator of hsp gene activity, are formed in the cells. PMID- 1607380 TI - Biosynthesis of lipoprotein: location of nascent apoAI and apoB in the rough endoplasmic reticulum of chicken hepatocytes. AB - Our previous studies showed that in hepatic RER of young chickens, nascent apoAI is not associated with lipoprotein particles and only becomes part of these lipoprotein structures in the Golgi. In this study, we have used three different methodologies to determine the locations of apoAI and apoB in the RER and compared them to that of albumin. Immunoelectron microscopic examination of the RER cell fractions showed that both apoAI and apoB were associated only with the RER membrane whereas albumin was located both within the lumen and on the limiting membrane of the vesicles. To examine the possibility of membrane integration of nascent apoAI and apoB in the RER, we administered L-[3H]leucine to young chickens for 10 min, isolated RER, treated this cell fraction with buffers of varying pH, and measured the release of radioactive albumin, apoAI, and apoB. The majority of nascent apoAI (64%), nascent apoB (100%), and nascent albumin (97%) was released from RER vesicles at pH 11.2, suggesting that, like albumin, apolipoproteins are not integrated within the membrane. To determine if nascent apoproteins are exposed to the cytoplasmic surface, we administered L [3H]leucine to young chickens and at various times isolated RER and Golgi cell fractions. Radioactive RER and Golgi cell fractions were treated with exogenous protease and the percent of nascent apoAI and apoB accessible to proteolysis was determined and compared to that of albumin. At 5, 10, and 20 min of labeling, 35 56% of nascent apoAI and 60-75% of apoB in RER were degraded, while albumin was refractive to this treatment. At all times both apolipoproteins and albumin present in Golgi cell fractions were protected from proteolysis. These biochemical and morphological findings indicate that apoAI and apoB are associated with the rough microsomal membrane and are partially exposed to the cytoplasmic surface at early stages of secretion. They may later enter the luminal side of the ER and, on entering the Golgi, form lipoprotein particles. PMID- 1607382 TI - Translocation of the glucose transporter (GLUT4) to the cell surface in permeabilized 3T3-L1 adipocytes: effects of ATP insulin, and GTP gamma S and localization of GLUT4 to clathrin lattices. AB - Insulin stimulates the movement of two glucose transporter isoforms (GLUT1 and GLUT4) to the plasma membrane (PM) in adipocytes. To study this process we have prepared highly purified PM fragments by gently sonicating 3T3-L1 adipocytes grown on glass coverslips. Using confocal laser immunofluorescence microscopy we observed increased PM labeling for GLUT1 (2.3-fold) and GLUT4 (eightfold) after insulin treatment in intact cells. EM immunolabeling of PM fragments indicated that in the nonstimulated state GLUT4 was mainly localized to flat clathrin lattices. Whereas GLUT4 labeling of clathrin lattices was only slightly increased after insulin treatment, labeling of uncoated PM regions was markedly increased with insulin. These data suggest that GLUT4 recycles from the cell surface both in the presence and absence of insulin. In streptolysin-O permeabilized adipocytes, insulin, and GTP gamma S increased PM levels of GLUT4 to a similar extent as observed with insulin in intact cells. In the absence of an exogenous ATP source the magnitude of these effects was considerably reduced. Removal of ATP per se caused a significant increase in cell surface levels of GLUT4 suggesting that ATP may be required for intracellular sequestration of these transporters. When insulin and GTP gamma S were added together, in the presence of ATP, PM GLUT4 levels were similar to levels observed when either insulin or GTP gamma S was added individually. Addition of GTP gamma S was able to overcome this ATP dependence of insulin-stimulated GLUT4 movement. GTP gamma S had no effect on constitutive secretion of adipsin in permeabilized cells. In addition, there was no effect of insulin or GTP gamma S on GLUT4 movement to the PM in noninsulin sensitive streptolysin-O-permeabilized 3T3-L1 fibroblasts overexpressing GLUT4. We conclude that the insulin-stimulated movement of GLUT4 to the cell surface in adipocytes may require ATP early in the insulin signaling pathway and a GTP-binding protein(s) at a later step(s). We propose that the association of GLUT4 with clathrin lattices may be important in maintaining the exclusive intracellular location of this transporter in the absence of insulin. PMID- 1607381 TI - 100-kD proteins of Golgi- and trans-Golgi network-associated coated vesicles have related but distinct membrane binding properties. AB - The 100-110-kD proteins (alpha-, beta-, beta'-, and gamma-adaptins) of clathrin coated vesicles and the 110-kD protein (beta-COP) of the nonclathrin-coated vesicles that mediate constitutive transport through the Golgi have homologous protein sequences. To determine whether homologous processes are involved in assembly of the two types of coated vesicles, the membrane binding properties of their coat proteins were compared. After treatment of MDBK cells with the fungal metabolite Brefeldin A (BFA), beta-COP was redistributed to the cytoplasm within 15 s, gamma-adaptin and clathrin in the trans-Golgi network (TGN) dispersed within 30 s, but the alpha-adaptin and clathrin present on coated pits and vesicles derived from the plasma membrane remained membrane associated even after a 15-min exposure to BFA. In PtK1 cells and MDCK cells, BFA did not affect beta COP binding or Golgi morphology but still induced redistribution of gamma-adaptin and clathrin from TGN membranes to the cytoplasm. Thus BFA affects the binding of coat proteins to membranes in the Golgi region (Golgi apparatus and TGN) but not plasma membranes. However, the Golgi binding interactions of beta-COP and gamma adaptin are distinct and differentially sensitive to BFA. BFA treatment did not release gamma-adaptin or clathrin from purified clathrin-coated vesicles, suggesting that their distribution to the cytoplasm after BFA treatment of cells was due to interference with their rebinding to TGN membranes after a normal cycle of disassembly. This was confirmed using an in vitro assay in which gamma adaptin binding to TGN membranes was blocked by BFA and enhanced by GTP gamma S, similar to the binding of beta-COP to Golgi membranes. These results suggest the involvement of GTP-dependent proteins in the association of the 100-kD coat proteins with membranes in the Golgi region of the cell. PMID- 1607383 TI - Proteolysis of the major yolk glycoproteins is regulated by acidification of the yolk platelets in sea urchin embryos. AB - The precise function of the yolk platelets of sea urchin embryos during early development is unknown. We have shown previously that the chemical composition of the yolk platelets remains unchanged in terms of phospholipid, triglyceride, hexose, sialic acid, RNA, and total protein content after fertilization and early development. However, the platelet is not entirely static because the major 160 kD yolk glycoprotein YP-160 undergoes limited, step-wise proteolytic cleavage during early development. Based on previous studies by us and others, it has been postulated that yolk platelets become acidified during development, leading to the activation of a cathepsin B-like yolk proteinase that is believed to be responsible for the degradation of the major yolk glycoprotein. To investigate this possibility, we studied the effect of addition of chloroquine, which prevents acidification of lysosomes. Consistent with the postulated requirement for acidification, it was found that chloroquine blocked YP-160 breakdown but had no effect on embryonic development. To directly test the possibility that acidification of the yolk platelets over the course of development temporally correlated with YP-160 proteolysis, we added 3-(2,4-dinitroanilo)-3-amino-N methyldipropylamine (DAMP) to eggs or embryos. This compound localizes to acidic organelles and can be detected in these organelles by EM. The results of these studies revealed that yolk platelets did, in fact, become transiently acidified during development. This acidification occurred at the same time as yolk protein proteolysis, i.e., at 6 h after fertilization (64-cell stage) in Strongylocentrotus purpuratus and at 48 h after fertilization (late gastrula) in L. pictus. Furthermore, the pH value at the point of maximal acidification of the yolk platelets in vivo was equal to the pH optimum of the enzyme measured in vitro, indicating that this acidification is sufficient to activate the enzyme. For both S. purpuratus and Lytechinus pictus, the observed decrease in the pH was approximately 0.8 U, from 7.0 to 6.2. The trypsin inhibitor benzamidine was found to inhibit the yolk proteinase in vivo. By virtue of the fact that this inhibitor was reversible we established that the activity of the yolk proteinase is developmentally regulated even though the enzyme is present throughout the course of development. These findings indicate that acidification of yolk platelets is a developmentally regulated process that is a prerequisite to initiation of the catabolism of the major yolk glycoprotein. PMID- 1607384 TI - Actin-facilitated assembly of smooth muscle myosin induces formation of actomyosin fibrils. AB - To identify regulatory mechanisms potentially involved in formation of actomyosin structures in smooth muscle cells, the influence of F-actin on smooth muscle myosin assembly was examined. In physiologically relevant buffers, AMPPNP binding to myosin caused transition to the soluble 10S myosin conformation due to trapping of nucleotide at the active sites. The resulting 10S myosin-AMPPNP complex was highly stable and thick filament assembly was suppressed. However, upon addition to F-actin, myosin readily assembled to form thick filaments. Furthermore, myosin assembly caused rearrangement of actin filament networks into actomyosin fibers composed of coaligned F-actin and myosin thick filaments. Severin-induced fragmentation of actin in actomyosin fibers resulted in immediate disassembly of myosin thick filaments, demonstrating that actin filaments were indispensable for mediating myosin assembly in the presence of AMPPNP. Actomyosin fibers also formed after addition of F-actin to nonphosphorylated 10S myosin monomers containing the products of ATP hydrolysis trapped at the active site. The resulting fibers were rapidly disassembled after addition of millimolar MgATP and consequent transition of myosin to the soluble 10S state. However, reassembly of myosin filaments in the presence of MgATP and F-actin could be induced by phosphorylation of myosin P-light chains, causing regeneration of actomyosin fiber bundles. The results indicate that actomyosin fibers can be spontaneously formed by F-actin-mediated assembly of smooth muscle myosin. Moreover, induction of actomyosin fibers by myosin light chain phosphorylation in the presence of actin filament networks provides a plausible hypothesis for contractile fiber assembly in situ. PMID- 1607385 TI - Release of myosin II from the membrane-cytoskeleton of Dictyostelium discoideum mediated by heavy-chain phosphorylation at the foci within the cortical actin network. AB - Membrane-cytoskeletons were prepared from Dictyostelium amebas, and networks of actin and myosin II filaments were visualized on the exposed cytoplasmic surfaces of the cell membranes by fluorescence staining (Yumura, S., and T. Kitanishi Yumura. 1990. Cell Struct. Funct. 15:355-364). Addition of ATP caused contraction of the cytoskeleton with aggregation of part of actin into several foci within the network, but most of myosin II was released via the foci. However, in the presence of 10 mM MgCl2, which stabilized myosin II filaments, myosin II remained at the foci. Ultrastructural examination revealed that, after contraction, only traces of monomeric myosin II remained at the foci. By contrast, myosin II filaments remained in the foci in the presence of 10 mM MgCl2. These observations suggest that myosin II was released not in a filamentous form but in a monomeric form. Using [gamma 32P]ATP, we found that the heavy chains of myosin II released from membrane-cytoskeletons were phosphorylated, and this phosphorylation resulted in disassembly of myosin filaments. Using ITP (a substrate for myosin II ATPase) and/or ATP gamma S (a substrate for myosin II heavy-chain kinase [MHCK]), we demonstrated that phosphorylation of myosin heavy chains occurred at the foci within the actin network, a result that suggests that MHCK was localized at the foci. These results together indicate that, during contraction, the heavy chains of myosin II that have moved toward the foci within the actin network are phosphorylated by a specific MHCK, with the resultant disassembly of filaments which are finally released from membrane-cytoskeletons. This series of reactions could represent the mechanism for the relocation of myosin II from the cortical region to the endoplasm. PMID- 1607386 TI - Localization and specificity of the phospholipid and actin binding sites on the tail of Acanthamoeba myosin IC. AB - We used bacterially expressed beta-galactosidase fusion proteins to localize the phospholipid binding domain of Acanthamoeba myosin IC to the region between amino acids 701 and 888 in the NH2-terminal half of the tail. Using a novel immobilized ligand lipid binding assay, we determined that myosin I can bind to several different acidic phospholipids, and that binding requires a minimum of 5 mol% acidic phospholipid in a neutral lipid background. The presence of di- and triglycerides and sterols in the lipid bilayer do not contribute to the affinity of myosin I for membranes. We confirm that the ATP-insensitive actin binding site is contained in the COOH-terminal 30 kD of the tail as previously shown for Acanthamoeba myosin IA. We conclude that the association of the myosin IC tail with acidic phospholipid head groups supplies much of the energy for binding myosin I to biological membranes, but probably not specificity for targeting myosin I isoforms to different cellular locations. PMID- 1607387 TI - Gas2, a growth arrest-specific protein, is a component of the microfilament network system. AB - In this report we analyze the protein product of a growth arrest-specific gene, gas2, by means of an affinity-purified antibody raised against the protein produced in bacteria. The regulation of Gas2 biosynthesis reflects the pattern of mRNA expression (Schneider, C., R. King, and L. Philipson. 1988. Cell. 54:787 793): its relative level is tightly associated with growth arrest. Gas2 seems to be regulated also at the posttranslational level via a phosphorylation mechanism. Gas2 is well conserved during the evolution with the same apparent molecular mass (36 kD) between mouse and human. We also demonstrate that Gas2 is a component of the microfilament system. It colocalizes with actin fiber, at the cell border and also along the stress fiber, in growth-arrested NIH 3T3 cells. The pattern of distribution, detected in arrested cells, can also be observed in growing cells when they are microinjected with the purified GST-Gas2 protein. In none of the analyzed oncogene-transformed NIH 3T3 cell lines was Gas2 expression induced under serum starvation. PMID- 1607388 TI - Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal domain with cytoplasmic microtubules in transfected CV-1 cells. AB - To understand the interactions between the microtubule-based motor protein kinesin and intracellular components, we have expressed the kinesin heavy chain and its different domains in CV-1 monkey kidney epithelial cells and examined their distributions by immunofluorescence microscopy. For this study, we cloned and sequenced cDNAs encoding a kinesin heavy chain from a human placental library. The human kinesin heavy chain exhibits a high level of sequence identity to the previously cloned invertebrate kinesin heavy chains; homologies between the COOH-terminal domain of human and invertebrate kinesins and the nonmotor domain of the Aspergillus kinesin-like protein bimC were also found. The gene encoding the human kinesin heavy chain also contains a small upstream open reading frame in a G-C rich 5' untranslated region, features that are associated with translational regulation in certain mRNAs. After transient expression in CV 1 cells, the kinesin heavy chain showed both a diffuse distribution and a filamentous staining pattern that coaligned with microtubules but not vimentin intermediate filaments. Altering the number and distribution of microtubules with taxol or nocodazole produced corresponding changes in the localization of the expressed kinesin heavy chain. The expressed NH2-terminal motor and the COOH terminal tail domains, but not the alpha-helical coiled coil rod domain, also colocalized with microtubules. The finding that both the kinesin motor and tail domains can interact with cytoplasmic microtubules raises the possibility that kinesin could crossbridge and induce sliding between microtubules under certain circumstances. PMID- 1607389 TI - Separate domains of KAR1 mediate distinct functions in mitosis and nuclear fusion. AB - The yeast KAR1 gene is essential for mitotic growth and important for nuclear fusion. Mutations in KAR1 prevent duplication of the spindle pole body (SPB), and affect functions associated with both the nuclear and cytoplasmic microtubules. The localization of hybrid Kar1-lacZ proteins, described elsewhere (Vallen, E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press), suggest that the protein is associated with the SPB. In this paper, we report a deletion analysis demonstrating that the mitotic and karyogamy functions of KAR1 are separate and independent, residing in discrete functional domains. One region, here shown to be essential for mitosis, coincided with a part of the protein that is both necessary and sufficient to target Karl-lacZ hybrid proteins to the SPB (Vallen, E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press). Complementation testing demonstrated that deletions in this interval did not affect nuclear fusion. A second region, required only for karyogamy, was necessary for the localization of a Kar3-lacZ hybrid protein to the SPB. These data suggest a model for the roles of Kar1p and Kar3p, a kinesin-like protein, in nuclear fusion. Finally, a third region of KAR1 was found to be important for both mitosis and karyogamy. This domain included the hydrophobic carboxy terminus and is sufficient to target a lacZ-Kar1 hybrid protein to the nuclear envelope (Vallen E. A., T. Y. Scherson, T. Roberts, K. van Zee, and M. D. Rose. 1992. Cell. In press). Altogether, the essential mitotic regions of KAR1 comprised 20% of the coding sequence. We propose a model for Kar1p in which the protein is composed of several protein-binding domains tethered to the nuclear envelope via its hydrophobic tail. PMID- 1607390 TI - Flagellar microtubule dynamics in Chlamydomonas: cytochalasin D induces periods of microtubule shortening and elongation; and colchicine induces disassembly of the distal, but not proximal, half of the flagellum. AB - To study the mechanisms responsible for the regulation of flagellar length, we examined the effects of colchicine and Cytochalasin D (CD) on the growth and maintenance of Chlamydomonas flagella on motile wild type cells as well as on pf 18 cells, whose flagella lack the central microtubules and are immobile. CD had no effect on the regeneration of flagella after deflagellation but it induced fully assembled flagella to shorten at an average rate of 0.03 microns-min. Cells remained fully motile in CD and even stubby flagella continued to move, indicating that flagellar shortening did not selectively disrupt machinery necessary for motility. To observe the effects of the drug on individual cells, pf 18 cells were treated with CD and flagella on cells were monitored by direct observation over a 5-hour period. Flagella on control pf 18 cells maintained their initial lengths throughout the experiment but flagella on CD-treated cells exhibited periods of elongation, shortening, and regrowth suggestive of the dynamic behavior of cytoplasmic microtubules observed in vitro and in vitro. Cells behaved individually, with no two cells exhibiting the same flagellar behavior at any given time although both flagella on any single cell behaved identically. The rate of drug-induced flagellar shortening and elongation in pf 18 cells varied from 0.08 to 0.17 microns-min-1, with each event occurring over 10-60-min periods. Addition of colchicine to wild type and pf 18 cells induced flagella to shorten at an average rate of 0.06 microns-min-1 until the flagella reached an average of 73% of their initial length, after which they exhibited no further shortening or elongation. Cells treated with colchicine and CD exhibited nearly complete flagellar resorption, with little variation in flagellar length among cells. The effects of these drugs were reversible and flagella grew to normal stable lengths after drug removal. Taken together, these results show that the distal half to one-third of the Chlamydomonas flagellum is relatively unstable in the presence of colchicine but that the proximal half to two-thirds of the flagellum is stable to this drug. In contrast to colchicine, CD can induce nearly complete flagellar microtubule disassembly as well as flagellar assembly. Flagellar microtubules must, therefore, be inherently unstable, and flagellar length is stabilized by factors that are sensitive, either directly or indirectly, to the effects of CD. PMID- 1607391 TI - Evidence for heterophilic adhesion of embryonic retinal cells and neuroblastoma cells to substratum-adsorbed NCAM. AB - The adhesion of embryonic chicken retinal cells and mouse N2A neuroblastoma cells to purified embryonic chicken retinal NCAM adsorbed on a solid substratum was examined using a quantitative centrifugal adhesion assay. Both cell types adhered to NCAM and the adhesion was specifically inhibited by monovalent anti-NCAM antibody fragments. N2A cell adhesion depended on the amount of NCAM applied to the substratum, was cation independent, and was insensitive to treatment with the cytoskeletal perturbing drugs colchicine and cytochalasin D. These results indicated that the tubulin and actin cytoskeletons were not critically required for adhesion to NCAM and make it unlikely that the cell surface ligand for NCAM is an integrin. Adhesion was however temperature dependent, strengthening greatly after a brief incubation at 37 degrees C. CHO cells transfected with NCAM cDNAs did not adhere specifically to substratum-bound NCAM and pretreatment of N2A cells and retinal cells with anti-NCAM antibodies did not inhibit adhesion to substratum-bound NCAM. These results suggest that a heterophilic interaction between substratum-adsorbed NCAM and a non-NCAM ligand on the surface of the probe cells affects adhesion in this system and support the possibility that heterophilic adhesion may be a function of NCAM in vivo. PMID- 1607394 TI - RUBIDIUM, a program for computer-aided assignment of two-dimensional NMR spectra of polypeptides. AB - Taking advantage of the rule-based expert system technology, a program named RUBIDIUM (Rule-Based Identification In 2D NMR Spectrum) was developed to accomplish the automatic 1H NMR resonance assignments of polypeptides. Besides noise elimination and peak selection capabilities, RUBIDIUM detects the cross peak patterns of amino acid residues in the COSY spectrum, assigning these patterns to amino acid types, performing sequential assignments using combined COSY/NOESY spectra, and finally, achieving the total assignment of the 1H NMR spectrum. PMID- 1607393 TI - Malaria sporozoites and circumsporozoite proteins bind specifically to sulfated glycoconjugates. AB - Circumsporozoite (CS) proteins, which densely coat malaria (Plasmodia) sporozoites, contain an amino acid sequence that is homologous to segments in other proteins which bind specifically to sulfated glycoconjugates. The presence of this homology suggests that sporozoites and CS proteins may also bind sulfated glycoconjugates. To test this hypothesis, recombinant P. yoelii CS protein was examined for binding to sulfated glycoconjugate-Sepharoses. CS protein bound avidly to heparin-, fucoidan-, and dextran sulfate-Sepharose, but bound comparatively poorly to chondroitin sulfate A- or C-Sepharose. CS protein also bound with significantly lower affinity to a heparan sulfate biosynthesis deficient mutant cell line compared with the wild-type line, consistent with the possibility that the protein also binds to sulfated glycoconjugates on the surfaces of cells. This possibility is consistent with the observation that CS protein binding to hepatocytes, cells invaded by sporozoites during the primary stage of malaria infection, was inhibited by fucoidan, pentosan polysulfate, and heparin. The effects of sulfated glycoconjugates on sporozoite infectivity were also determined. P. berghei sporozoites bound specifically to sulfatide (galactosyl[3-sulfate]beta 1-1ceramide), but not to comparable levels of cholesterol-3-sulfate, or several examples of neutral glycosphingolipids, gangliosides, or phospholipids. Sporozoite invasion into hepatocytes was inhibited by fucoidan, heparin, and dextran sulfate, paralleling the observed binding of CS protein to the corresponding Sepharose derivatives. These sulfated glycoconjugates blocked invasion by inhibiting an event occurring within 3 h of combining sporozoites and hepatocytes. Sporozoite infectivity in mice was significantly inhibited by dextran sulfate 500,000 and fucoidan. Taken together, these data indicate that CS proteins bind selectively to certain sulfated glycoconjugates, that sporozoite infectivity can be inhibited by such compounds, and that invasion of host hepatocytes by sporozoites may involve interactions with these types of compounds. PMID- 1607392 TI - Cell surface phosphatidylinositol-anchored heparan sulfate proteoglycan initiates mouse melanoma cell adhesion to a fibronectin-derived, heparin-binding synthetic peptide. AB - Cell surface heparan sulfate proteoglycan (HSPG) from metastatic mouse melanoma cells initiates cell adhesion to the synthetic peptide FN-C/H II, a heparin binding peptide from the 33-kD A chain-derived fragment of fibronectin. Mouse melanoma cell adhesion to FN-C/H II was sensitive to soluble heparin and pretreatment of mouse melanoma cells with heparitinase. In contrast, cell adhesion to the fibronectin synthetic peptide CS1 is mediated through an alpha 4 beta 1 integrin and was resistant to heparin or heparitinase treatment. Mouse melanoma cell HSPG was metabolically labeled with [35S]sulfate and extracted with detergent. After HPLC-DEAE purification, 35S-HSPG eluted from a dissociative CL 4B column with a Kav approximately 0.45, while 35S-heparan sulfate (HS) chains eluted with a Kav approximately 0.62. The HSPG contained a major 63-kD core protein after heparitinase digestion. Polyclonal antibodies generated against HSPG purified from mouse melanoma cells grown in vivo also identified a 63-kD core protein. This HSPG is an integral plasma membrane component by virtue of its binding to Octyl Sepharose affinity columns and that anti-HSPG antibody staining exhibited a cell surface localization. The HSPG is anchored to the cell surface through phosphatidylinositol (PI) linkages, as evidenced in part by the ability of PI-specific phospholipase C to eliminate binding of the detergent-extracted HSPG to Octyl Sepharose. Furthermore, the mouse melanoma HSPG core protein could be metabolically labeled with 3H-ethanolamine. The involvement of mouse melanoma cell surface HSPG in cell adhesion to fibronectin was also demonstrated by the ability of anti-HSPG antibodies and anti-HSPG IgG Fab monomers to inhibit mouse melanoma cell adhesion to FN-C/H II. 35S-HSPG and 35S-HS bind to FN-C/H II affinity columns and require 0.25 M NaCl for elution. However, heparitinase treated 125I-labeled HSPG failed to bind FN-C/H II, suggesting that HS, and not HSPG core protein, binds FN-C/H II. These data support the hypothesis that a phosphatidylinositol-anchored HSPG on mouse melanoma cells (MPIHP-63) initiates recognition to FN-C/H II, and implicate PI-associated signal transduction pathways in mediating melanoma cell adhesion to this defined ligand. PMID- 1607396 TI - Primary tuberculosis of the glans penis. PMID- 1607395 TI - Compare-Conformer: a program for the rapid comparison of molecular conformers based on interatomic distances and torsion angles. AB - A computer program for comparison of the conformations of a number of related molecular structures is described. The comparisons are performed on either interatomic distances or torsion angles. The comparisons are accomplished on ordered pairs of distances or torsion angles, and the distance comparisons can be performed in a manner that allows permutation of the distance pairs being compared. The algorithm utilizes bit-string Boolean operations that allow the comparisons to be performed rapidly. The program should be useful for computer assisted molecular modeling studies in which the viable conformers of bioactive analogues are compared in order to locate those conformers that place key substituents in the same spatial orientation. PMID- 1607397 TI - Oral tetracycline rinse improves symptoms of white sponge nevus. PMID- 1607398 TI - Chronic leukocytoclastic vasculitis associated with polycythemia vera: effective control with pentoxifylline. PMID- 1607399 TI - Subcutaneous administration of methotrexate. PMID- 1607400 TI - Systemic treatment of extensive condylomata acuminata with interferon alfa-2b. PMID- 1607401 TI - Cutaneous T-cell lymphoma and autoimmune hemolytic anemia. PMID- 1607402 TI - Annular dystrophic calcinosis cutis in an infant. PMID- 1607403 TI - Combined Aspergillus and zygomycotic (Rhizopus) infection in a patient with acquired immunodeficiency syndrome. Presentation as inflammatory tinea capitis. PMID- 1607404 TI - In memoriam a tribute to Abraham Buschke. PMID- 1607405 TI - How many epidermal nevus syndromes exist? PMID- 1607406 TI - Cutaneous manifestations of thyroid disease. AB - Cutaneous manifestations of thyroid disease are protean in nature and affect all age groups. This review focuses on normal thyroid gland physiology, specific cutaneous/thyroid lesions such as the thyroglossal duct cyst and metastatic thyroid malignancies, nonspecific cutaneous alterations of the hyperthyroid and hypothyroid states, and the numerous associations of thyroid disease with other cutaneous and/or systemic disorders. PMID- 1607407 TI - Differential expression of adhesion molecules on infiltrating cells in inflammatory dermatoses. AB - BACKGROUND: Adhesion molecules and their ligands are involved in coordination of the activities of the immune system. OBJECTIVE: To evaluate whether adhesion molecules are relevant in the pathogenesis of inflammatory dermatoses, we analyzed the expression pattern of many of these molecules. METHODS: The expression of 10 members of the integrin and immunoglobulin superfamilies was mapped by means of immunohistochemical techniques in biopsy specimens of psoriasis (n = 15), pityriasis lichenoides (n = 11), parapsoriasis en plaques (n = 11), contact dermatitis (n = 7), and lichen planus (n = 5). RESULTS: In all investigated skin diseases, almost every infiltrating cell expressed lymphocyte function-associated antigens 1 and 3 as well as very late activation (VLA) antigens 4 and 5. The subepidermal infiltrate differed with regard to the expression of VLA-1, VLA-3, and VLA-6, which was high in lichen planus and moderate or absent in the other dermatoses. The intraepidermal lymphocytes in psoriasis and pityriasis lichenoides were VLA-1 positive, whereas the subepidermal infiltrate lacked this marker. CONCLUSION: The differential upregulation of adhesion molecules in the mononuclear infiltrate and on keratinocytes demonstrates their importance in the pathogenesis of cutaneous inflammation. PMID- 1607408 TI - Who discovers melanoma? Patterns from a population-based survey. AB - BACKGROUND: Melanoma is external and potentially detectable by many persons but little is known about who first discovers these lesions. An understanding of discovery patterns can shape future public and professional education programs. OBJECTIVE: Our purpose was to assess patterns of melanoma discovery and to determine the patients' role in finding their own lesions. METHODS: With a written, mailed questionnaire, we conducted a population-based statewide survey of 216 incident cases of melanoma in Massachusetts. RESULTS: Approximately half (53%) of melanomas were self-discovered, whereas the remainder were detected by medical providers (26%), family members (17%), and others (3%). Nearly one third of persons said they could not see their own lesions easily. Compared with men, women were more likely to discover their own lesions (66% vs 42%, p = 0.001) and those on their spouses (23% vs 2%, p less than 0.001). CONCLUSION: Improving early detection and reducing mortality of melanoma will require both public and professional education programs, with particular emphasis on targeting men at highest risk of this disease. PMID- 1607409 TI - Epidemiologic evidence for the role of melanocytic nevi as risk markers and direct precursors of cutaneous malignant melanoma. Results of a case control study in melanoma patients and nonmelanoma control subjects. AB - BACKGROUND: Melanocytic nevi (MN) are markers of melanoma risk, but their potential role as precursors of cutaneous malignant melanoma (CMM) is still controversial. OBJECTIVE: The overall and site-specific relative risk (RR) of developing CMM was evaluated according to site-specific MN counts. METHODS: MN prevalence by anatomic site and by age was compared in 200 CMM patients and in 200 nonmelanoma control subjects; RRs were calculated. RESULTS: In CMM patients both MN and CMM were mainly found on the legs in women and on the posterior trunk in men, whereas in the control subjects most MN were found on the arms. MN counts on the trunk in men and on the legs in women were best predictors of the overall CMM risk (RR: 33-fold and 15-fold, respectively, for greater than 20 vs up to 4 MN). For both genders combined, the RR for CMM developing on the trunk and legs (predominant CMM locations) was best predicted by MN counts in the respective body region (RR: 24-fold and 27-fold, respectively). MN prevalence peaked in the fourth to fifth decade of life and most CMM were diagnosed during the fifth and sixth decades. CONCLUSION: The site-specificity of melanoma risk found for high MN counts on the trunk and the legs and the close similarities in age distribution suggest that the role of MN as direct precursors of CMM has been underestimated and exceeds the number of histologically evident MN associated with CMM. PMID- 1607410 TI - The psychological effects of androgenetic alopecia in men. AB - BACKGROUND: Despite the prevalence of androgenetic alopecia among men, little is known about its psychological effects. OBJECTIVE: This investigation examined the psychosocial sequelae that balding men attribute to hair loss and compared balding and nonbalding men in personality functioning. METHODS: Subjects included 63 men with modest balding, 40 men with more extensive balding, and 42 nonbalding controls. All anonymously completed a battery of standardized psychological measures. RESULTS: Reported effects of balding reflected considerable preoccupation, moderate stress or distress, and copious coping efforts. These effects were especially salient among men with more extensive balding and among younger men, single men, and those with an earlier hair-loss onset. Relative to controls, balding men had less body-image satisfaction yet were comparable on other personality indexes. Personality correlates of the psychological responses to hair loss were identified. CONCLUSION: Although most men regard hair loss to be an unwanted, distressing experience that diminishes their body image, balding men actively cope and generally retain the integrity of their personality functioning. PMID- 1607411 TI - Burning mouth syndrome: a possible etiologic role for local contact hypersensitivity. AB - BACKGROUND: The pathogenesis of the burning mouth syndrome (BMS) is not yet understood. Apart from psychologic factors, several etiologic "somatic" factors have been reported. OBJECTIVE: In 22 patients (19 women, 3 men, mean age 56 years) classified with BMS, clinical and laboratory investigations were performed, with particular emphasis on the role of contact hypersensitivity. Twenty of the 22 patients wore a complete or partial denture. METHODS: Besides clinical and laboratory investigations patch testing was performed with a standard routine series and a standardized denture-dental (acrylate and metal) series. RESULTS: Folate, iron, pyridoxine deficiency, and Candida infections were found, but correction of the deficiency or treatment of the infection was of no benefit. Contact allergy to allergens used in the production of acrylate-based dentures was observed in six (27%) of the cases (all wore a denture); positive reactions were seen to N,N,-dimethyl-4-toluidine (3 cases), to 4 tolyldiethanolamine (2 cases), to benzoylperoxide (2 cases), and to oligotriacrylate (1 case). In six cases (27%) a possible relevant sensitization was seen to dental metals and in particular to gold chloride (four cases). CONCLUSION: The possible role of local hypersensitivity reactions to denture or dental components as etiologic factors in BMS must be considered. PMID- 1607412 TI - Etretinate increases carcinoembryonic antigen in palmar scrapings. AB - BACKGROUND: Retinoids can affect epithelial structure and function. Patients who take etretinate can develop stickiness of their palms and soles. OBJECTIVE: We measured carcinoembryonic antigen, a representative glycoprotein in palmar scrapings, to see whether levels were increased in patients taking etretinate when compared with a variety of controls. METHODS: Carcinoembryonic antigen was measured by a standard immunoassay in scrapings taken from the palm. RESULTS: Carcinoembryonic antigen is increased in palmar scrapings in patients taking etretinate. CONCLUSION: Etretinate usage may affect sweat gland function or possibly adherence of carcinoembryonic antigen to surface keratinocytes. The presence of increased amounts of glycoprotein on the surface of the skin may explain the stickiness often noted by patients taking etretinate. PMID- 1607413 TI - Presence of anti-basal cell antibodies in oral lichen planus. AB - BACKGROUND: An autoimmune hypothesis for oral lichen planus (OLP) has been proposed, but no anti-basal cell antibodies (anti-BCA) have been found in the sera of patients with OLP. OBJECTIVE: Our purpose was to test whether the negative results of anti-BCA assays in sera have been due to the insensitivity of the substrates. Rat esophagus, monkey esophagus, as well as human oral mucosa and skin were used to detect anti-BCA in sera of OLP patients. METHODS: By indirect immunofluorescence technique, the rat esophagus was found to be the most sensitive substrate. Therefore it was used as the only substrate to test the presence of anti-epithelial cell antibodies (anti-ECA) in a large group of patients with OLP and other oral mucosal diseases or normal control subjects. RESULTS: The results showed that anti-ECA were detected in 54% (34 of 63) of patients with OLP, 71% (15 of 21) of patients with aphthous ulcers, 29% (6 of 21) of patients with oral carcinoma, 20% (2 of 10) of patients with traumatic ulcer, and 7% (1 of 15) of patients with periodontitis but none of the healthy control subjects (n = 41). The presence of anti-BCA in OLP patients' sera was persistent and lasted for a few months or years. There was a decrease in the serum anti-BCA titers in six of eight anti-BCA-positive OLP patients after topical application of triamcinolone. CONCLUSION: These anti-BCA that persist longer in OLP patients' sera may be autoantibodies that are raised against altered basal cell-specific antigens. PMID- 1607414 TI - Genital benign chronic pemphigus (Hailey-Hailey disease) presenting as condylomas. AB - BACKGROUND: Genital lesion sof benign chronic pemphigus (FBCP)(Hailey-Hailey disease) may present as verrucous papules. Genital warts and papular acantholytic dyskeratosis of the genitalia may be considered in the differential diagnosis. OBJECTIVE: Our purpose was to describe the clinical characteristics and histologic features of verrucous anogenital FBCP. METHODS: Six patients, five women and one man, with verrucous anogenital lesions of FBCP, initially diagnosed as warts, were examined and biopsy specimens were evaluated histologically. RESULTS: The lesions were located exclusively in the perineal and perianal regions with axillary involvement in one case. Family history was negative in three of the six cases. Histologic examination confirmed the diagnosis of FBCP but was significant for the absence of crusts and the presence of only minimal inflammation. CONCLUSION: Our cases and the literature are reviewed with the conclusion that all verrucoid genital lesions with the histologic characteristics of Hailey-Hailey disease may represent FBCP. PMID- 1607416 TI - Combined treatment with oral etretinate and electron beam therapy in patients with cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome). AB - BACKGROUND: Total skin irradiation for early-stage mycosis fungoides produces clinical remission in 90% of patients, but the median duration of remission is only 2 to 4 years. Etretinate has proven efficacy in advanced mycosis fungoides. Its potential as adjuvant therapy to radiation could be limited by toxicity from the combination. OBJECTIVE: Our purpose was to determine whether oral etretinate at 1 mg/kg can be combined with 35 Gy of radiation without intensifying or prolonging the radiation reaction and to determine the relapse-free survival rate. METHODS: Twenty-three patients began etretinate on day one of radiation and the dose was reduced for nose bleeds, dry skin, or hyperlipidemia. During the reaction skin toxicity questionnaires were completed weekly. Nine concurrent patients receiving only radiation completed identical forms. RESULTS: Etretinate did not intensify the skin reaction but did prolong it by 2 weeks. At a median follow-up of 2 years the relapse-free survival rate in complete responders was similar to stage-matched concurrent and historic control subjects. CONCLUSIONS: Both radiation and etretinate can be given together with acceptable toxicity and without compromising either therapy. PMID- 1607415 TI - Efficacy of a 1-week, twice-daily regimen of terbinafine 1% cream in the treatment of interdigital tinea pedis. Results of placebo-controlled, double blind, multicenter trials. AB - BACKGROUND: Patients with tinea pedis often discontinue treatment before eradication of the fungus when their symptoms improve. The result is an incomplete cure/recurrence. OBJECTIVE: Terbinafine, a topical fungicidal agent, was evaluated in double-blind, placebo-controlled trials (159 patients) for its ability to achieve cure and relief of symptoms in the same time frame, that is, before compliance wanes. METHODS: Mycologic characteristics (with potassium hydroxide examination and culture) and clinical signs and symptoms were assessed at baseline, at the end of a 1-week, twice-daily treatment and at 1, 3, and 5 weeks after the completion of therapy. RESULTS: Both terbinafine and vehicle provided early relief of symptoms. However, only terbinafine gave progressive mycologic improvement such that at 5 weeks after treatment, 88% of the patients receiving terbinafine had converted from positive to negative mycology compared with 23% of the patients treated with vehicle. CONCLUSION: The rapid and potent fungicidal action of terbinafine results in a high cure rate in interdigital tinea pedis with 1 week of treatment and may avoid failures caused by non compliance. PMID- 1607417 TI - Immunophenotypic and genotypic characterization of lymphomatoid papulosis. AB - BACKGROUND: Lymphomatoid papulosis (LyP) is a chronic dermatosis that histologically resembles malignant lymphoma. Thus far, only a few cases of LyP have been characterized in detail with regard to immunophenotype, genotype, and karyotype. OBJECTIVE: Our purpose was to study seven patients with LyP and compare the results to those reported in the literature. METHODS: Skin biopsy specimens were analyzed by frozen section immunohistochemical and molecular biologic techniques. Cytogenetic analysis was also performed in three cases. RESULTS: The atypical lymphoid cells consisted of activated helper T cells; four of the seven patients had lesions with a detectable clonal T-cell population. A peripheral T-cell lymphoma developed in one patient before the emergence of a genotypically different LyP T-cell clone. Cytogenetic studies were abnormal in one case of LyP and normal in another, whereas the karyotype of the lymphoma was abnormal. CONCLUSION: LyP is a preneoplastic proliferation of activated helper T cells, which is often clonal and may regress and expand with the development of new LyP clones or lymphoma. PMID- 1607418 TI - Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma of the skin, ear, and lip. Implications for treatment modality selection. AB - We reviewed all studies since 1940 on the prognosis of squamous cell carcinoma (SCC) of the skin and lip. The following variables are correlated with local recurrence and metastatic rates: (1) treatment modality, (2) prior treatment, (3) location, (4) size, (5) depth, (6) histologic differentiation, (7) histologic evidence of perineural involvement, (8) precipitating factors other than ultraviolet light, and (9) host immunosuppression. Local recurrences occur less frequently when SCC is treated by Mohs micrographic surgery. This local recurrence rate differential in favor of Mohs micrographic surgery holds true for primary SCC of the skin and lip (3.1% vs 10.9%), for ear SCC (5.3% vs 18.7%), for locally recurrent (previously treated) SCC (10% vs 23.3%), for SCC with perineural involvement (0% vs 47%), for SCC of size greater than 2 cm (25.2% vs 41.7%), and for SCC that is poorly differentiated (32.6% vs 53.6%). PMID- 1607419 TI - American Academy of Dermatology Patch Testing Survey: use and effectiveness of this procedure. AB - The results of an American Academy of Dermatology (AAD)-sponsored survey on the use and effectiveness of patch testing are presented. Academy members' responses indicate that 27% do not patch test at all. Reasons given for not testing included (1) the patient history was adequate for diagnosis, (2) patch testing was too time-consuming, and (3) reimbursement was not sufficient. Dermatologists in residency training programs who responded to a similar survey are testing frequently and report a high degree of positivity and relevancy among tests applied. Recommendations are presented with a focus toward increasing interest in patch testing among the membership. PMID- 1607420 TI - First International Congress of Dermatology and Syphilology, Paris, Aug. 5-10, 1889. PMID- 1607422 TI - A comparison between a 1986 and 1989 cohort of inner-city adolescent females on knowledge, beliefs, and risk factors for AIDS. AB - In order to assess changes from 1986 to 1989 in knowledge, beliefs, and risk factors for AIDS, the responses of inner-city adolescent girls were compared. Although 63% of the 1989 cohort received AIDS education in school, the base knowledge of the two cohorts was not markedly different. Between 1986 and 1989, the number of sexual partners increased for adolescents of all ethnic groups, yet concerns about AIDS showed a decline. Those adolescents who had the highest number of sexual partners were also those who had the most knowledge and most concerns about AIDS. Implications for preventive education focus on ethnic diversity and gaps between adolescent knowledge and behavior. PMID- 1607421 TI - Truancy and illegal drug use, and knowledge of HIV infection in 932 14-16-year old adolescents. AB - In a sample of 932 4th & 5th year comprehensive school adolescents, 41% had truanted in the current term. The truants, compared with their non-truanting peers, had three times the level of solvent misuse (14% compared with 4%), thrice the soft drug misuse (19% compared with 6%), and four times the involvement with hard drugs (9% compared with 2%). Truants were significantly more involved with other problematic behaviour and were found to score higher on all negative social indices, including parents who smoked. Despite the sample's relatively accurate knowledge about drugs and HIV infection, truants scored less well on these and other HIV-related issues. An extrapolation of the results indicates a significant number of adolescents at risk demanding urgent policy initiatives. PMID- 1607423 TI - Glue sniffing: a comparison study of sniffers and non-sniffers. AB - A study of 22 glue sniffers and 22 non-sniffers was carried out with individuals from the same reference group. The subjects were all street children living in supervised shelters. No statistically significant differences were found between the sniffers and non-sniffers on cognitive measures or biographical features (e.g. time spent at school, years on the street). When rated by shelter staff on a modified version of the Christiansen Rating Scale (1967) the sniffers were perceived to be significantly more disturbed in their relationships with others, however, methodological issues do not permit conclusive evidence of behavioural differences to be drawn. The authors conclude that the findings lend support for the view that the effects of volatile substance abuse on cognitive and personality functioning cannot be clearly demonstrated. PMID- 1607424 TI - Friendship and personal adjustment during adolescence. AB - A questionnaire evaluating the friendship network, the expectations towards friends, the level of intimacy and attachment with friends, as well as the presence of conflicts with friends, was administered to 349 adolescents. The sample consisted of both males and females, age ranging from 12 to 18 years. Subjects were also given various personal adjustment indices that were obtained from the Offer Self Image Questionnaire. The results demonstrate that there are small differences in the friendship network across age and gender. Analysis of the qualitative aspects of friendship are generally constant with respect to age, but demonstrate marked differences with respect to gender: girls expect more from their friends than boys and their level of attachment and intimacy with friends is greater. The results also indicate that the number of friends in the network is not significantly correlated with the personal adjustment variables. Multiple regression analyses revealed that the quality of attachment maintained with friends and the absence of conflict experiences in friendship account for a low but significant proportion of the score variance obtained from the personal adjustment scale. The possibility to confer personal problems and the preoccupations to friends seems beneficial for the acquisition of adaptive behavior. Deficiencies in communication with friends or confrontation experiences and feelings of alienation are related to some forms of maladaptive behavior. PMID- 1607425 TI - Chronic self-destructive behavior in normative and delinquent adolescents. AB - The Chronic Self-Destructiveness Scale (CSDS) and the Psychopathic Deviate and Hypomania scales of the MMPI were administered to 112 delinquent adolescents and to 141 high-school students. Both male and female delinquents reported significantly higher levels of chronic self-destructiveness. Significant positive correlations between the CSDS and the MMPI scales were found for all groups. The results indicate that delinquent males have high levels of chronic self destructiveness attributable to these personality variables; however, other cultural variables may intervene. The results for delinquent females were similar to those of high-school males. Thus, these findings raise questions about societal influences and the definitions of delinquent behavior. PMID- 1607426 TI - Coping strategies used by adolescents in dealing with family relocation overseas. AB - This study investigated: (a) the types of coping strategies adolescents commonly employ in response to family relocation overseas; and (b) whether sex, age, self concept, behavioral adjustment, and previous history of moves affect the types of strategies used by these sojourners. For this purpose, we selected a widely used model of coping which distinguishes between approach and avoidance strategies and a sample of teenagers whose families had recently relocated in Belgium. Four assessment instruments were utilized: the Background Information Data Sheet, the Stress Response Scale, the Piers-Harris Children's Self-Concept Scale, and the Coping Responses Inventory--Youth Form. Results indicated that adolescent sojourners selected both approach and avoidance strategies to cope with family relocation overseas. Correlational analyses further showed that females and older teenagers tended to rely significantly more on approach strategies than on avoidance strategies. Self-concept and behavioral adjustment were also found to be related to the type coping strategies employed, while the history of previous relocation was not. PMID- 1607427 TI - The relationship between self-esteem and psychological adjustment in young adolescents. AB - The study adopts a multi-dimensional construct of self-esteem to examine the relationship between self-perception and psychological adjustment in order to identify specific dimensions that discriminate between disturbed and non disturbed groups. The disturbed group (n = 33) is derived from a clinical sample and are matched with a non-disturbed group (n = 33) of adolescents. Results indicate that dimensional self-concept scores are significantly lower for clinical subjects while there are no significant differences between groups on the mathematics, honesty, and physical ability dimensions. These findings provide a more fine grained understanding of the relationship between self-esteem and psychological adjustment and emphasize the need to examine self-esteem in terms of its particular dimensions. PMID- 1607428 TI - Strengthening of feldspathic porcelain by ion exchange and tempering. AB - This study investigated the effectiveness of tempering and ion-exchange treatments on crack growth and bi-axial flexural strength of seven feldspathic porcelains. The results showed that tempering treatment was more effective in strengthening porcelain than was the ion-exchange process as measured by the bi axial flexural strength. However, the results of initial crack size induced by a microhardness tester showed that ion-exchange yielded a surface that was more resistant to crack initiation than was that yielded by the tempering treatment. EDX and microprobe analyses showed that there was evidence of exchange between Na+ within the porcelain surface and K+ from the ion-exchange agent applied on the surface. PMID- 1607429 TI - Analysis of tempering stresses in bilayered porcelain discs. AB - Previous studies of opaque-porcelain/body-porcelain discs have shown that compressive stresses which develop in the porcelain surface by being tempered in air can inhibit the sizes of cracks induced within the surface. The objective of this study was to develop a theoretical model for analysis of transient and residual stresses in opaque-porcelain/body-porcelain discs which were produced under variable cooling conditions. The model incorporates the effects of stress and structural relaxation. Transient and residual stresses were calculated for bilayered porcelain discs 16 mm in diameter and 2 mm in thickness for three opaque-porcelain/body-porcelain combinations. Transient temperature distributions in the discs for simulated convective cooling were calculated by finite-element analysis. Data from microhardness indentations reported by Anusavice et al. (1989) indicate that crack lengths measured for bilayered porcelain discs subjected to slow cooling conditions, for which the model predicted residual tensile stresses, were greater than those combinations for which residual compressive stresses were calculated. Calculated values of residual compressive stress for tempered specimens were considerably higher than those for specimens that were slowly cooled and those that were cooled by free convection. In general, residual stress levels calculated by use of the analytical model were in fairly good agreement with the trends observed for crack lengths and bi-axial flexural strengths reported by Anusavice and Hojjatie (1991). The results of the present study indicate that a visco-elastic model is a viable approach for determination of transient and residual stresses in opaque-porcelain/body porcelain discs. PMID- 1607430 TI - Fatigue behavior of direct post-and-core-restored premolars. AB - Evaluation of long-term mechanical behavior of new types of restorations in clinical trials is time-consuming. A partial alternative can be found in experimental fatigue-testing, which simulates accelerated mechanical deterioration. The aim of this study was to determine the feasibility of using fatigue-testing of a complex dental restoration and to evaluate the mechanical fatigue behavior of premolar teeth restored with a titanium alloy post and an amalgam or composite core. Eighty-seven human upper premolar teeth were decoronated, embedded, and restored with a prefabricated post of 1 mm diameter. The teeth were randomly assigned to one of two groups corresponding with a core build-up of amalgam or chemically-cured core composite, respectively. Five to 21 days after restoration, the specimens were subjected to cyclic loading (frequency, 5 Hz), at an angle of 45 degrees to the long axis of the tooth. The boundary technique was used for determination of the mean fatigue strengths of the restorations at 10(4), 10(5), and 10(6) cycles, simulating up to 1-3 years of clinical functioning. Mean fatigue strength was expressed in percentage of initial strength: For 10(4), 10(5), and 10(6) cycles, the results were 66%, 58%, and 52%, respectively, for the amalgam and 62%, 62%, and 53% for the composite group. It is concluded that fatigue-testing of more complex systems is possible, if a suitable testing method is selected. The restorations showed a comparable strength reduction after 10(6) cycles of about 50% of their initial strength. The composite core build-up showed a behavior less predictable than that of the amalgam, which might be attributed to handling parameters. PMID- 1607431 TI - Effectiveness of oxide films in reducing mercury release from amalgams. AB - The release of mercury from four freshly-triturated amalgams into air, argon, and moist air environments was quantitated at three different temperatures. Although a measurable amount of mercury was released from dental amalgam, the evaporation rate was immediately reduced by several phenomena, the most important being the formation of an oxide film on the surface. This hypothesis was supported by the fact that release rates were elevated in an inert argon environment, but declined dramatically once air was introduced and oxidation could occur. The further amalgamation of "free" mercury, as well as the presence of water vapor, also contributed to the reduced release rates observed during aging. Mercury release was reduced to a negligible level within three to four hours after trituration. Only one of the amalgams, Tytin, demonstrated a thermal dependence for mercury release in air. The results of this study suggest that the exposure to mercury vapor from a freshly placed amalgam restoration would be negligible in consideration of the normal estimated daily intake from all other sources. PMID- 1607432 TI - The effect of an experimental chewable antiplaque preparation containing chlorhexidine on plaque and gingival index scores. AB - This clinical cross-over trial investigated the effects of a chewable preparation containing chorhexidine-fluoride-xylitol, xylitol control tablets, or chlorhexidine mouthwash, twice daily, on plaque and gingival index scores of subjects refraining from mechanical cleaning of their teeth. Both preparations containing chlorhexidine were found to be efficient antiplaque agents when compared with the control. There was no statistically significant difference between the tablet preparation and conventional chlorhexidine rinsings with respect to the recorded parameters. Thus, an efficient antiplaque preparation can be made in tablet form, which may have advantages in instances where use of mouthwash solutions is impracticable. PMID- 1607433 TI - pH regulation by Streptococcus mutans. AB - The intracellular pH (pHi) optimum for glycolysis in Streptococcus mutans Ingbritt was determined to be 7.0 by use of the ionophore gramicidin for manipulation of pHi. Glycolytic activity decreased to zero as the pHi was lowered from 7.0 to 5.0. In contrast, glycolysis had an extracellular pH (pHo) optimum of 6.0 with a much broader profile. The relative insensitivity of glycolysis to the lowering of pHo was attributed to the ability of S. mutans to maintain a transmembrane pH gradient (delta pH, inside more alkaline) at low pHo. At a pHo of 5.0, glycolyzing cells of S. mutans maintained a delta pH of 1.37 +/- 0.09 units. The maintenance of this delta pH was dependent on the concentration of potassium ions in the extracellular medium. Potassium was rapidly taken up by glycolyzing cells of S. mutans at a rate of 70 nmol/mg dry weight/min. This uptake was dependent on the presence of both ATP and a proton motive-force (delta p). The addition of N-N'-dicyclohexylcarbodiimide (DCCD) to glycolyzing cells of S. mutans caused a partial collapse of the delta pH. Growth of S. mutants at pHo 5.5 in continuous culture resulted in the maintenance of a delta pH larger than that produced by cells grown at pH 7.0. These results suggest the presence of a proton-translocating F1Fo-ATPase in S. mutans whose activity is regulated by the intracellular pH and transmembrane electrical potential (delta psi). The production of an artificial delta p of 124 mV across the cell membrane of S. mutans did not result in proton movement through the F1Fo-ATPase coupled to ATP synthesis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607434 TI - The effects of sucralose, xylitol, and sorbitol on remineralization of caries lesions in rats. AB - The purpose of this study was to determine whether ingestion of sucralose, xylitol, sorbitol, or distilled water alone could enhance remineralization of early caries lesions in rats. Rats were infected by Streptococcus sobrinus, fed diet 2000 (Ziegler Brothers, Gardners, PA) ad libitum for two weeks, and, in addition, were offered drinking water sweetened by sucrose (10% w/v). A group of rats terminated at this time displayed significant levels of sulcal and smooth surface caries. The remaining animals, for the ensuing three weeks, either continued on the same cariogenic challenge or received their essential nutrition by gavage and drank water, sweetened by one of the agents listed above, ad libitum. At the end of the additional three-week period, animals receiving sucralose, xylitol, sorbitol, or distilled water had fewer lesions than did the animals terminated after the two-week cariogenic challenge. The results show that removal of the cariogenic challenge allowed remineralization to occur and that no sweetening agent was superior to another in this respect. PMID- 1607435 TI - A study of the ability of an in situ remineralization model to differentiate between the effects of two fluoride dentifrices that produced significantly different clinical caries results. AB - The purpose of this study was to determine whether an in situ remineralization model was able to show a difference in the effects of two dentifrices of different fluoride concentrations and significantly different clinical efficacies. Three dentifrices were tested in a double-blind, cross-over study design. The products contained 0 ppm F, 250 ppm F, or 1000 ppm F from sodium fluoride and were formulated with a silica base according to the formulations used in a human caries trial (Koch et al., 1990). Nineteen subjects each carried three or four thin sections of enamel in their partial dentures. The thin sections, containing artificial caries lesions, were covered with a steel mesh to provide space for plaque formation and then brushed in situ three times daily with the dentifrices. Following the two-week treatment periods, the specimens were removed from the dentures and analyzed for changes in mineral content. The findings showed that the placebo dentifrice (0 ppm F) resulted in 56.8 +/- 74.3% demineralization, the 250-ppm-F dentifrice produced 12.9 +/- 41.3% demineralization, thereby showing partial caries protection, and the 1000-ppm-F dentifrice produced 17.3 +/- 32.1% remineralization. Linear regression analysis showed that the percent remineralization was significantly related to the fluoride concentration in the dentifrice (p less than 0.001). The 250-ppm-F dentifrice was also significantly less effective than the 100-ppm-F dentifrice (p = 0.04, one-tailed Fisher Protected LSD test). These findings are in accord with the human caries trial and support the use of the present in situ remineralization model for prediction of the anticaries efficacy of fluoride dentifrice products. PMID- 1607436 TI - Dentinogenic activity of allogenic plasma fibronectin on dog dental pulp. AB - The response of ectomesenchymal cells of dog dental pulp to implantation of Millipore filters supplemented with bovine plasma fibronectin was evaluated after observation periods of one or four weeks. Two concentrations of plasma fibronectin were used (0.2 and 1 mg/mL). Experiments also included implants treated with control solutions (PBS or 1 mg/mL of dog albumin). Formation of a layer of elongated, polarized cells was demonstrated in direct contact with the implants treated with 1 mg/mL of plasma fibronectin solution, after one week post operatively. Microfilamentous organization and orientation of rough endoplasmic reticulum was observed mainly in the supranuclear zone of the polarized cells. Implants treated with the same solution were consistently surrounded by a thick layer of dentinal matrix after four weeks of their exposure to pulp sites. Implants treated with control solutions or with the low concentration of fibronectin never showed any sign of cell polarization and matrix synthesis. These data provide evidence that the pulp cells can express their odontoblastic phenotype in response to a surface containing concentrated fibronectin (even allogenic), without the need of other molecules as exogenous inductive factors. PMID- 1607438 TI - Changing patterns of fluoride intake. Workshop. Chapel Hill, April 23-25, 1991. PMID- 1607437 TI - An immunohistochemical study of the distribution of immunocompetent cells, especially macrophages and Ia antigen-expressing cells of heterogeneous populations, in normal rat molar pulp. AB - The precise distribution of various immunocompetent cells in rat molar pulp was immunohistochemically examined by use of seven anti-rat monoclonal antibodies. It was demonstrated that rat molar pulp contained many OX6 (anti-Ia antigen) positive cells and a large number of ED1 (anti-monocytes, macrophages, and dendritic cells)-positive, ED2 (anti-tissue macrophages)-positive, and/or OX35 (anti-macrophages and CD4+ lymphocytes)-positive cells. Macrophage-like cells predominated in the central portion of the pulp, while cells of dendritic appearance usually existed in the periphery of the pulp. Double-immunoperoxidase staining revealed that these cells showed some heterogeneity, but the majority could be classified as ED1+/OX6-/ED2+ cells, which may be Ia-histiocytes. Findings also suggested that true dendritic cells may be included in the ED1+/OX6+/ED2- category of cells. A small number of T lymphocytes and plasma cells were also detected. These results suggest that the normal dental pulp contains a variety of immunocompetent cells, with macrophages as the most dominating. Following the exogenous invasion of pathogenic stimuli in the pulp, these cells may participate in the defense reaction by acting as phagocytes or antigen-presenting cells, which are essential for the initiation of immune responses. PMID- 1607439 TI - The changing patterns of systemic fluoride intake. AB - Fluorosis prevalence has increased in North America since the 1930's-1940's. It may also have increased since 1970, though the evidence for that is less clear. Continued monitoring will help determine whether increased fluorosis prevalence in children in the United States is a cohort effect from the 1970's. This review considers the evidence for an increase in fluoride ingestion from all sources since the 1970's. If an increase has occurred, the most likely sources are fluoride dietary supplements, inadvertent swallowing of fluoride toothpastes, and increased fluoride in food and beverages. For adults, there is no evidence from dietary surveys to show that fluoride intake has increased over the last generation. Dietary surveys for children aged six months to two years are similarly inconclusive, though the great variation in fluoride content of various infant foods might be obscuring real effects. The data on fluoride intake by children from food and beverages, infant foods included, are not strong enough to conclude that an increase in fluoride ingestion has occurred since the 1970's. However, the suggested upper limit of fluoride intake is substantially being reached in many children by ingestion of fluoride from food and drink (0.2-0.3 mg per day) and from fluoride toothpaste (0.2-0.3 mg per day). Two public health issues that arise from this review are: (a) the need for a downward revision in the schedule for fluoride supplementation, and (b) education on the potential for high fluoride concentration of soft drinks and processed fruit juices. PMID- 1607440 TI - Biological mechanisms of fluorosis and level and timing of systemic exposure to fluoride with respect to fluorosis. AB - Enamel fluorosis can occur following either an acute or chronic exposure to fluoride during tooth formation. Fluorosed enamel is characterized by a retention of amelogenins in the early-maturation stage, and by the formation of a more porous enamel with a subsurface hypomineralization. The mechanisms by which fluoride affects enamel development include specific effects on both the ameloblasts and on the developing enamel matrix. Maturation-stage ameloblast modulation is more rapid in fluorosed enamel as compared with control enamel, and proteolytic activity in fluorosed early-maturation enamel is reduced as compared with controls. Secretory enamel appears to be more susceptible to the effects of fluoride following acute fluoride exposure, such as may occur with the use of fluoride supplements. However, both human and animal studies show that the transition/early-maturation stage of enamel formation is most susceptible to the effects of chronic fluoride ingestion at above-optimal levels of fluoride in drinking water. PMID- 1607441 TI - The level and timing of systemic exposure to fluoride with respect to caries resistance. AB - Material related to water fluoridation and fluoride availability has been examined for changing patterns of fluoride intake by humans over recent years. The difficulty of separating systemic and topical fluoride action from water and foods from that found in fluoride agents used in preventive treatment programs is discussed. Recommendations are made that water fluoridation is a well-proven program and should be continued, but that fluoride supplementation programs under the control of the individual should be carefully evaluated and, if used, should be restricted to periods after the secretory stage of enamel formation is normally finished for anterior teeth, with supplements commenced during the pre eruption maturation period and continuing until permanent tooth eruption is complete. Although supplements can also give a topical source to the teeth, depending on the way the supplement is consumed and the duration of time it is available in the mouth, other methods of topical fluoride provision are endorsed, and these should continue through life. It is suggested, in respect of epidemiology studies, that data collected before the availability of fluoride dentifrices in 1971 should be re-examined. PMID- 1607442 TI - Acute and chronic fluoride toxicity. PMID- 1607443 TI - Current regulations and recommendations concerning water fluoridation, fluoride supplements, and topical fluoride agents. AB - In recent years, an increase in the prevalence of dental fluorosis, mostly of the very mild to mild category, has been seen in the United States. This paper therefore discusses the safety of dental fluoride products, primarily with respect to the risk of dental fluorosis due to chronic ingestion of these products by pre-school children. No change is indicated in the optimal fluoride level (0.7 to 1.2 ppm) for water fluoridation. A reduction in the dosage of fluoride supplements is recommended for children aged from three to six years (14.5 to 22 kg body weight) residing in communities with less than 0.7 ppm F. Physicians, pharmacists, and dentists need to be better educated in correctly prescribing fluoride supplements; such prescriptions should be based on the fluoride concentration of the domestic water supply and the child's weight/height/age. No change is recommended in the concentration of fluoride used in dentifrices and mouthrinses. The US Food and Drug Administration should require more explicit labeling of fluoride products with regard to avoidance of ingestion, use of small amounts, and need for supervised use by pre-school children. The efficacy of water fluoridation, fluoride supplements, and topical fluoride agents has been amply documented elsewhere. PMID- 1607444 TI - Bridging the gap between laboratory research and clinical practice--dentists doing dental materials research. PMID- 1607445 TI - The kind of reality training that's needed in dental education today. PMID- 1607446 TI - The advisory panel recommendations for the dental profession for the 21st century. PMID- 1607447 TI - Commentary on "Education for dental practice in the year 2005: a beginning dialogue". PMID- 1607448 TI - Reactions to the recommendations. PMID- 1607449 TI - It's so hard to have a dialogue with yourself. PMID- 1607450 TI - A longitudinal study of dental students' personality type preferences. AB - The Myers-Briggs Type Indicator was administered to five classes of students at the beginning and end of their dental education. The 161 students who completed both tests were categorized according to personality type. The Spearman rank order correlation of the two sets of data was calculated and tested. Changes in personality type between the tests were noted using two different standards. The first standard defined change as any alteration in the four-letter MBTI designation and thus was a measure of change in type. The second standard defined change utilizing the 95 percent confidence interval of the continuous score of each of the four MBTI scales and thus was a measure of change in the underlying construct, personality. The first standard indicated 75.8 percent of students change type; the second indicated 11.2 percent changed personality. These data are consistent with previously reported studies, but raise questions regarding what is being measured and how the data are being analyzed. PMID- 1607451 TI - Assessing the organizational climate in dental schools. PMID- 1607452 TI - A research training program for dental faculty. PMID- 1607453 TI - A preclinical model for exodontia. PMID- 1607454 TI - Dental school faculty and association membership. PMID- 1607455 TI - If you build it, they will come. PMID- 1607457 TI - Curriculum guidelines for microbiology. PMID- 1607456 TI - Curriculum guidelines for education in substance abuse, alcoholism, and other chemical dependencies. PMID- 1607458 TI - Autografting and PUVA. A combination therapy for vitiligo. AB - A novel approach to the management of vitiligo is described using a combination of epidermal autografts transplanted into the depigmented areas and psoralen ultraviolet-A (PUVA) therapy. Epidermal autografts can be obtained rapidly and in large numbers using a device that combines the synergistic effects of suction and heat on the skin. Subsequent exposure to PUVA therapy promotes spread of pigmentation out of the grafts resulting in even and complete pigmentation. In certain situations, the combination therapy appears to offer the potential for avoiding the disadvantages of both of the two treatments when they are used alone. This article presents our preliminary work in the development of the methodology for this combined approach. PMID- 1607459 TI - Mucoepidermoid carcinoma metastatic to the skin. An histologic mimic of a primary sweat gland carcinoma. AB - Mucoepidermoid carcinomas are tumors that usually arise from salivary glands and have a characteristic histologic pattern of atypical squamous cells showing focal mucin production. Mucoepidermoid carcinomas are uncommon neoplasms that metastasize most commonly via lymphatic and hematogenous channels. We report what we believe to be the first case of a mucoepidermoid carcinoma arising from a sublingual salivary gland with metastasis to a distant site on the skin. The patient is a 58-year-old black woman who was initially diagnosed with a high grade mucoepidermoid carcinoma of the salivary glands of the tongue. Approximately 18 months after presentation, and 6 months following surgery, chemotherapy, and radiation therapy, the patient noted a firm nodule on her flank. Biopsy showed malignant squamous epithelium. Periodic acid-Schiff and alcian blue stains revealed focal mucin production. The histologic differential diagnosis included an eccrine carcinoma, mucin-producing adenocarcinoma with squamous differentiation, a primary cutaneous adenosquamous (mucoepidermoid) carcinoma and a malignant mixed tumor of the skin. Clinical correlation was essential in making the correct diagnosis. While mucoepidermoid carcinomas only uncommonly show distant metastasis, and even less frequently involve the skin, this entity should be included in the differential diagnosis of mucin-producing neoplasms in the skin. PMID- 1607460 TI - Neuroendocrine carcinoma of the skin (Merkel cell carcinoma) in a black. AB - Neuroendocrine carcinoma of the skin is an uncommon, small-cell neoplasm most commonly found on white, sun-exposed skin. Diagnosis by clinical and histologic means may be difficult. Immunohistochemical and ultrastructural analysis are often required. Because of the aggressive nature of neuroendocrine carcinoma of the skin, prompt diagnosis and treatment are essential. We present the rare occurrence of a neuroendocrine carcinoma of the skin on sun protected skin in a black. Clinical, histologic, immunohistochemical, and ultrastructural features are reviewed, and therapeutic options are discussed. PMID- 1607461 TI - Patient selection, hair transplant design, and hairstyle. AB - This article re-evaluates the parameters for selecting patients for hair transplant surgery and re-examines the design for the procedure. It also coordinates the hair transplant designs with hairstyles. PMID- 1607462 TI - Treatment of chronic erosions of junctional epidermolysis bullosa with human epidermal allografts. AB - We have successfully treated chronic central facial erosions of a patient with junctional epidermolysis bullosa using cultured epidermal allografts. Keratinocytes isolated from a skin biopsy of the patient's biological mother were used to generate the epidermal allografts. Significant re-epithelialization occurred during the course of four grafting procedures. Cultured epidermal allografts appear to be a promising method for treatment of chronic erosions of junctional epidermolysis bullosa. PMID- 1607463 TI - Do telangiectases communicate with the deep venous system? AB - Telangiectases of the legs occur frequently, with most patients seeking treatment for cosmetic reasons. Sclerotherapy continues to gain popularity as a safe and valuable therapeutic approach; however, deep vein thrombosis as well as pulmonary embolism have been reported even after sclerotherapy of small intradermal venectases. Hoping to uncover anatomic risk factors predisposing a patient to iatrogenic thrombosis, we investigated 15 patients with telangiectases of the legs applying ascending venography concomitantly with direct injection of the telangiectases. A digital radiographic technique was used as an imaging system. In two patients an unrestrained flow of the contrast medium into the venae femorales was noticed. As far as we know this is the first in vivo demonstration of venae communicantes connecting intradermal venectases to the deep veins. That means that particular anatomic conditions favor the spillage of sclerosant into the deep veins, which might contribute to the development of iatrogenic deep vein thromboses in compression sclerotherapy. PMID- 1607464 TI - Pericapillary fibrin cuffs in venous ulceration. Persistence with treatment and during ulcer healing. AB - A recent hypothesis suggests that venous hypertension leads to ulceration through the formation of pericapillary fibrin cuffs, which are presumed to impede the exchange of oxygen and other nutrients. In this report, we evaluated by direct immunofluorescence the presence of pericapillary fibrin at the edge of venous ulcers during the course of treatment with elastic compression. In an initial group of 23 patients studied at baseline, pericapillary fibrin cuffs were detected in 20 (91%) of 22 patients. The intensity of fibrin staining, rated blindly on a scale of 0 to 3, could not be correlated with several baseline parameters, including the clinical presence and extent of lipodermatosclerosis, ulcer size, venous recovery time, and transcutaneous oxygen measurements (TcPO2) taken next to the ulcer. Eleven of this initial group of 23 patients were randomly selected to receive elastic compression treatment, and were evaluated for the persistence of pericapillary fibrin at 60 and 120 days. Although a reduction (mean +/- SD = 50.2% +/- 25.7) in ulcer size occurred in 10 of the 11 patients, pericapillary fibrin was still present at the ulcer edge and with undiminished intensity. We conclude that pericapillary fibrin cuffs in venous ulcers persist with compression treatment and in spite of healing, and are unlikely to be directly related to the development of ulceration. PMID- 1607465 TI - Postsclerotherapy hyperpigmentation. Treatment with a flashlamp-excited pulsed dye laser. AB - Seventeen patients with 22 areas of postsclerotherapy hyperpigmentation lasting from 1 to 7 years were treated with a flashlamp-excited pulsed dye laser at 510 nm with a pulse duration of 300 nanoseconds between 2 to 3 J/cm2. Depth of hemosiderin pigmentation ranged from 0.2 to 2.8 mm. Forty-five percent of lesions lightened after treatment with significant lightening occurring in 27% of lesions. Four lesions in two patients developed postinflammatory hyperpigmentation after treatment. There was no significant difference in treatment response to pigment location or laser energy. PMID- 1607466 TI - Light reflection rheography. A non-invasive diagnostic tool for screening for venous disease. AB - Light reflection rheography has been increasingly used in the last few years to screen for chronic venous insufficiency. It is non-invasive, easy to perform, and well-suited for repetition and standardization. Light reflection rheography is appropriate for the global assessment of calf-pump insufficiency regardless of whether it is caused by varicosis, the postphlebitic syndrome, or deep venous thrombosis. For this reason, it is a good method to use as a pretreatment selection test, especially for varicose veins. With the application of tourniquets, it can help to predict treatment results. When it is used in combination with ultrasound venous Doppler, a simple decision can be made for the treatment of nearly all venous patients. PMID- 1607467 TI - The potential for fat transplantation. PMID- 1607468 TI - Mohs surgery update. Intraoperative presuturing. AB - During the course of Mohs surgery, the surgeon may be able to predict that the final closure may require tissue expansion or some other extraordinary measure to close a defect on a particular location. Presuturing, the use of stitches to preoperatively stretch donor tissue peripheral to the wound, has been previously advocated to aid in the primary closure of nonMohs tumor removal defects and scalp reduction defects. We describe the anticipatory need for and the use of button bolstered nonabsorbable sutures to stretch or expand the perioperative tissues for final closure. Previously unreported in the literature, we also employ this technique prior to flap closure. This quick and easy manouever following the intermediate and final stages of Mohs surgery has seen great use in the care of some relatively large tumors. PMID- 1607469 TI - Postsclerotherapy hyperpigmentation. PMID- 1607470 TI - Re: Burow's triangle or Schimanowski/Dieffenbach's wedge? PMID- 1607471 TI - Effect of methoprene and diflubenzuron on larval development of the cat flea (Siphonaptera: Pulicidae). AB - Cat flea larvae, Ctenocephalides felis Bouche, exposed to glass surfaces treated with methoprene concentrations from 0.127 to 1,270 ng/cm2 did not emerge as adults. Most larvae died in the third instar, but those exposed to the 0.127 ng/cm2 concentration formed larval-pupal intermediates. Larvae exposed to glass surface treated with diflubenzuron concentrations from 12.7 to 1,270 ng/cm2 died during the process of molting in all three instars. Exposure of larvae to 12.7 and 127 ng/cm2 diflubenzuron resulted in 15 and 5.2% adult emergence, respectively. PMID- 1607472 TI - Dietary effects of allopurinol and sulfinpyrazone on development, survival, and reproduction of German cockroaches (Dictyoptera: Blattellidae). AB - Diets containing two gout medications, allopurinol and sulfinpyrazone, were fed ad libitum to first- or second-instar German cockroaches for 15 wk or until 100% mortality was reached. Cockroaches fed greater than or equal to 0.10% allopurinol diets weighed significantly less than those fed the control diet. Mortality of cockroaches fed diets containing greater than or equal to 0.05% allopurinol was significantly greater than those fed the control diet. The LT50 (6.1 wk) of cockroaches fed diets containing 0.10% allopurinol was significantly less than those fed any other diet containing allopurinol. LT50s and slopes were proportional and inversely related, respectively, to percentage of allopurinol in the diet. The addition of sulfinpyrazone to allopurinol diets minimally enhanced the blatticidal nature of the diets. Nymphs fed diets containing greater than or equal to 0.05% allopurinol experienced significant delays in adult emergence. Cockroaches fed greater than or equal to 0.01% allopurinol diets aborted a significantly greater percentage of their oothecae than those fed the 0.001% allopurinol or control diets. Hatched oothecae from cockroaches fed the 0.01% allopurinol diet had significantly fewer nymphs than those fed the 0.001% allopurinol or control diets. Percentage of oothecae aborted and number of nymphs per hatched ootheca from cockroaches fed a 2% sulfinpyrazone diet did not differ significantly from the control. PMID- 1607473 TI - Differences in the response of German cockroach (Dictyoptera: Blattellidae) field strains to vapors of pyrethroid formulations. AB - Late-instar German cockroaches from an insecticide-susceptible field strain (Fairbanks) and four pyrethroid-resistant field strains were exposed to vapors of a cyfluthrin flowable concentrate (FC) and the formulation blank (formulation without the active ingredient). Experiments with other pyrethroid formulations were done with the Fairbanks strain and an insecticide-resistant field strain (K 851) because these strains exemplified the maximum interstrain variation in experiments with the FC. In these experiments, I used a cyfluthrin wettable powder (WP) and its blank, a cyfluthrin emulsifiable concentrate (EC), and a permethrin aerosol and its blank. Vapors of the FC and its blank caused the most rapid dispersal. Dispersal induced by vapors of the WP, EC, and aerosol formulations was low and variable. In general, less of a dispersal response occurred in the resistant strains than in the susceptible strain. The strain mostly highly resistant to pyrethroids (K-851) dispersed slowly compared with the other resistant strains in experiments with the FC and its blank. When vapor induced dispersal was relatively low (less than 50%), a trend was still evident towards less dispersal in the K-851 strain than in the Fairbanks strain. Although dispersal in experiments with the FC did not differ significantly from that in experiments with the FC formulation blank, mean percentage dispersal at the end of the experiments was higher with the formulation blanks than with the complete formulations in experiments with the WP and permethrin aerosol. PMID- 1607474 TI - Binomial sampling for pest management of stable flies (Diptera: Muscidae) that attack dairy cattle. AB - A binomial sampling plan for pest management of the stable fly, Stomoxys calcitrans (L.), was developed. Counts of stable flies on front legs of the same animal were independent and each leg from the same animal was considered a sample unit. The relationship between the mean number of flies per leg and the variance was determined and did not vary among farms. The relationship between the mean number of flies per leg and the proportion of legs with zero, one or less, and two or less flies (P0, P1, and P2) was determined and used as the basis of the binomial sampling plan. Predicted values of the mean number of flies per leg from P0, P1, and P2 were close to observed values of the mean number of flies per leg. Equations are presented for calculating the variance of a predicted value of the mean number of flies per leg using values of P0, P1 and P2 determined by sampling. Operating characteristic (OC) curves are also presented for determining the probability of making a treatment decision error at an economic threshold of one fly per leg (P0 = 0.47) using binomial sampling or direct counting. OC curves for binomial sampling with n = 50 legs were close to those for direct counting with n = 10 legs. Recommendations concerning the use of binomial sampling for stable flies are presented. PMID- 1607475 TI - Effects of disodium octaborate tetrahydrate on survival, behavior, and egg viability of adult muscoid flies (Diptera: Muscidae). AB - Disodium octaborate tetrahydrate (Na2B8O13(.)4H2O) was mixed with sugar and fed to adult Musca domestica L. and Fannia canicularis (L.) to determine concentration-mortality relationships. LC50s (48-h exposure) were 5.7% for M. domestica and 1.0% for F. canicularis. Rates of 1 and 2% were used to test effects on M. domestica mortality and egg hatch over an 8-d period. Reduced egg hatch was evident after 1 d of feeding on the treated mixtures and was greatest (less than 10% egg hatch) after flies fed only on treated mixtures for 2 d. A partial rebound in egg hatch occurred after 3-4 d of feeding on treated diet. Sperm motility in females fed treated sugar was apparently normal. Fertile egg placed on treated poultry manure did not hatch, indicating embryonic death, which also may have been involved in the low hatch of eggs observed from treated flies. When flies were exposed to treated sugar for 2 d then returned to untreated diet, delayed mortality effects and reduced egg hatch persisted for at least 3 d. Behavioral assays (feeding) with M. domestica demonstrated that flies rejected borate-sugar mixtures in favor of sugar alone when the concentration of borate was greater than 2%. Given a choice of treated and untreated poultry manure for oviposition, flies also rejected the treated manure. The potential of borates in adult bait formulations or applied to developmental substrates for fly control is discussed. PMID- 1607476 TI - Effects of low levels of lice and internal nematodes on weight gain and blood parameters in calves in central Texas. AB - The effects of low levels of both biting and sucking lice, a mixed population of nematodes, and a combination of all these parasites were evaluated in calves held in a barn with no environmental controls in central Texas. Observations at 122 sites on each animal for 16 wk consecutively in 1987 revealed that the largest numbers of all louse species [Haematopinus eurysternus (Nitzsch). Linognathus vituli (L.), and Bovicola bovis (L.)] occurred 3-7 wk after infestation. In 1988 L. vituli populations decreased rapidly after the 3rd wk and B. bovis remained fairly constant for 20 wk consecutively. Average nematode egg counts increased to approximately 300 eggs per gram of feces in 1987 and approximately 600 eggs per gram of feces in 1988. The nematodes Ostertagia ostertagia, Haemonchus placei, Oesophagostomum radiatum, Cooperia spp., and Trichostrongylus spp. were present at the end of the study in both years as determined by necropsy. No significant differences in erythrocyte count, mean cell volume, hematocrit, hemoglobin concentration, leukocyte counts, or serum albumin concentration were detected. However, significant increases in total serum protein concentration and serum globulin levels in calves harboring both groups of parasites were observed. Mean weight gain in calves infested with lice and nematodes was 11.4 and 10 kg less than that of uninfested controls during 16 wk in 1987 and 20 wk in 1988, respectively. PMID- 1607477 TI - Effects of radiation on spermatogenesis in Acarus siro L. (Acari: Acaridae). AB - Modifications of spermatogenesis and anatomy of male reproductive tracts caused by radiation (fast electrons) are described in Acarus siro and compared with data from other arthropod taxa. Radiation induced severe changes in gonial cells, including dilatation of endoplasmic reticulum and disruption of mitochondrial cristae. The latter sometimes created roundish myelin structures inside the mitochondrial matrix. Damage in developing cells caused an interruption of spermatogenesis and reduced the number of spermatids produced; high doses can cause sterility. PMID- 1607478 TI - Minimization of pesticide residues on head lettuce: within-head residue distribution of selected insecticides. AB - Pesticide use was simulated to determine the amount and location of pesticide residues within lettuce heads at harvest and to determine whether wrapper leaf removal reduced head residues. Excessive application of insecticides adversely affected head weight and total yield, independent of the direct effects of pests. Highest residues resulted from excessively high field use and minimum preharvest intervals. Wrapper leaf removal resulted in a low or residue-free head across all materials studied. PMID- 1607479 TI - Comparative effectiveness of avermectins and deltamethrin in suppressing oviposition in Lucilia cuprina (Diptera: Calliphoridae). AB - The activities of three avermectins and deltamethrin as oviposition suppressants were investigated with a laboratory bioassay in which gravid females of the blowfly Lucilia cuprina (Wiedemann) were exposed to treated oviposition targets. An easily comparable index of suppression, the oviposition suppression concentration (OSC), was defined. All four compounds were effective oviposition suppressants. The three avermectins had similar OSC50 values (approximately 13 ppm). Deltamethrin, with an OSC50 of 0.4 ppm, was the most potent suppressant. The avermectins all produced significant mortality in adults with suppressed oviposition, while deltamethrin did not cause an increase in deaths at concentrations giving up to 100% suppression of oviposition. The toxicities of all four compounds to adult females were similar when assessed by topical application. PMID- 1607480 TI - The ultrastructural histopathology of eosinophilic pustular folliculitis. AB - The follicular skin lesions of a patient with eosinophilic pustular folliculitis were investigated by electron microscopy. Pustules in the outer root sheath contained acantholytic keratinocytes with numerous microvilli and features of desmosomal cleavage. The infiltrating eosinophils and neutrophils exhibited autolytic or degenerative changes rather than degranulation. The aggregated tubulo-vesicular structures were associated with the debris of autolytic eosinophils. Multiple, tiny, bubble-like structures enclosed within a membrane were frequently seen in the intercellular space. The intercellular space of the outer root sheath was widened with decreased desmosomal adhesion between the keratinocytes, but no intracellular edema was detectable. The infiltrating lymphocytes, predominantly T-cells with convoluted nuclei, extended cytoplasmic processes to adjacent keratinocytes. Apposition of T-lymphocytes and Langerhans cells was noted. Some keratinocytes in the outer root sheath contained large, sebaceous lipid droplets. No obvious virus particles or other pathogenic agents were detected. It is possible that T-lymphocytes and other immunosurveillance cells are involved in the pathomechanism of eosinophilic pustular folliculitis. PMID- 1607481 TI - Eosinophil involvement in atopic dermatitis as reflected by elevated serum levels of eosinophil cationic protein. AB - Eosinophil cationic protein (ECP), one of the eosinophil granule proteins, is released during allergic reactions. We investigated the possibility of correlations among the serum levels of ECP, clinical activity, and eosinophil number in patients with atopic dermatitis (AD). Forty-four patients with AD and 25 normal, non-atopic subjects were studied. ECP was quantitated by a double antibody radioimmunoassay. The levels of serum ECP correlate with the grading of severity of clinical evaluations in AD. The patients with severe and moderate AD had significantly higher ECP concentrations than normal controls (p less than 0.001); mild AD had levels identical with those of control groups. A positive correlation was observed between the number of peripheral blood eosinophils and serum ECP levels in the severe cases (r = 0.67, p less than 0.05). Furthermore, these ECP levels significantly decreased in response to either improvement of clinical severity of AD or decreased numbers of blood hypodense eosinophils in anti-allergic drug-treated patients. No coefficient of correlation was observed between serum ECP and IgE levels. These findings indicate that eosinophils may release their granular contents, including ECP, into the peripheral circulation and/or inflammatory skin lesions and subsequently provoke a clinical exacerbation by stimulating allergic reactions. PMID- 1607482 TI - Cell proliferative activity of epidermal keratinocytes in hair discs. AB - To clarify the differences in epidermal keratinocyte proliferative activity and in postnatal developmental changes of this activity between the hair discs and the interfollicular epidermis, the incorporation of 3H-thymidine into the nuclei of the basal cells was measured by autoradiography, and the percentages of basal cells thus labelled were calculated. This percentage was higher in hair discs than in interfollicular epidermis at all stages examined. The percentage of labelled basal cells in the hair discs was 10% up to 15 days after birth, decreasing to about 6% from 20 days postnatally. These results suggest that the degree of cell proliferation in the hair disc epidermis differs from that in the surrounding epidermis and that changes in proliferative activity during the postnatal developmental stages are well correlated with the morphogenesis of the hair discs. PMID- 1607483 TI - Epidermal changes in active vitiligo. AB - Light and electron-microscopic studies were performed on the vitiligo and adjacent, normal appearing skin from 97 patients with actively spreading vitiligo and 19 patients with stable vitiligo. The vitiliginous skin revealed complete loss of pigment and melanocytes. In addition to degenerative changes in melanocytes, vacuolar changes of basal cells, epidermal infiltration of lymphocytes, dermal infiltration of lymphocytes, and melanophages in the upper dermis were also seen in the normal appearing skin adjacent to vitiliginous skin. These epidermal and dermal changes are more prominent in the skin of actively spreading vitiligo than in stable vitiligo. These findings suggest that the adjacent, normal appearing skin of actively spreading vitiligo shows some characteristic histopathologic findings, especially in the epidermis, indicating that cellular immunity could be involved in the pathogenesis of vitiligo. PMID- 1607484 TI - Immunogenetic study of three Japanese families with neonatal lupus erythematosus. AB - We encountered three Japanese families with neonatal lupus erythematosus. None of the three fathers showed any signs of collagen disease. The three mothers were found to suffer from Sjogren's syndrome; they all tested positive for anti-SSA and SSB antibodies and had lymphocyte infiltration into the small salivary gland. In two families, one child had neonatal lupus erythematosus while a sibling was normal; in the third family, both children had neonatal lupus erythematosus. Thus, a mother with positive anti-SSA and SSB antibodies can give birth to one infant with and one infant without or have two infants with neonatal lupus erythematosus. We conducted HLA typing of all 12 members of the three families in order to clarify the immunologic factors involved. We found no increased frequency of any HLA phenotype in the three mothers and their four children with neonatal lupus erythematosus; however, HLA-DR4 was present in three of the children with neonatal lupus erythematosus. PMID- 1607485 TI - Tsutsugamushi disease in the central part of Japan. AB - Two cases of tsutsugamushi disease misdiagnosed initially as drug eruption were reported. Clinical symptoms of both cases disappeared dramatically after starting minocycline. Statistical examinations were performed on 29 cases of tsutsugamushi disease, including those observed in Mie Prefecture since 1982. Half of them were seen in the last 2 years. The onset was predominantly recorded in November (59%). Presumptive sites of infection were forests (63%) and fields (21%). No patients were infected along river-banks. PMID- 1607487 TI - "Giant" senile sebaceous hyperplasia. AB - Although the usual size of senile sebaceous hyperplasia is 2 to 3 mm in diameter, we report one "giant" nodular case on the face. The patient is a 75-year-old Japanese man with a dome-shaped, skin-colored nodule on his right cheek. The lesion was 10 mm in diameter and had multiple small umbilications on its surface. He also had several small, yellow-colored, asymptomatic papules with central umbilication on his cheeks. Histologically, the giant nodule and the papule on the right cheek showed the same architectural pattern, a sharply demarcated hyperplasia of grouped mature sebaceous glands with a sebaceous converging duct, whose opening to the surface epithelium corresponded to the clinical umbilication. The reason for the giant growth of this senile sebaceous hyperplasia in our case is obscure; the patient had not been stressed by inductive agents or factors such as systemic corticosteroid and hemodialysis except for electrocoagulation on the lesion. In spite of the extraordinarily large size of the nodule, the conservative proliferating pattern seemed to show the benign hyperplastic character of senile sebaceous hyperplasia. PMID- 1607486 TI - Eruptive lichen planus. AB - We herein report a case of a rare variety of the acute eruptive form of lichen planus. The patient was a 51-year-old male who developed an intensely pruritic eruption on the lower legs which spread rapidly to all four extremities and trunk within a few months. The papulosquamous lesions were more than ten thousand in number. Topical steroid, cyclosporine, and systemic griseofulvin treatments were ineffective. However, there was a dramatic response to oral etretinate. PMID- 1607488 TI - Angiosarcoma of the thigh with thrombosis in the femoral artery. AB - We report a case of angiosarcoma with some peculiar clinical features developing on the left thigh of a 63-year-old man. The early primary lesion was erythematous with necrotic areas. The initial biopsy specimen of the lesion indicated a benign angioproliferative process. However, the necrotic area enlarged rapidly, ulcerated with severe pain, and thus was widely excised. The excised specimen had a malignant histologic appearance, particularly in the fascia, and was diagnosed as angiosarcoma. Following local recurrence, the lesion was complicated by thrombosis of the femoral artery at the affected site. A similar cutaneous lesion subsequently arose on the right lower leg, and thrombosis developed in the right femoral artery. Both legs had to be amputated. There were no distant metastases. PMID- 1607489 TI - Lipoatrophic diabetes. AB - A female patient with acanthosis nigricans, insulin resistant diabetes, and generalized lipoatrophy is reported. The patient developed skin pigmentation and acanthosis nigricans around the age of 34. Arthralgia, muscle weakness, and peripheral neuropathy were also present when she first visited us at 36 years of age. Dermatomyositis, systemic sclerosis, and internal malignancy were ruled out, and the diagnosis of acanthosis nigricans and insulin resistant diabetes was made. Her diabetes gradually worsened and, since the age of 39, she has been treated with an oral anti-diabetic drug. Around the age of 47, generalized lipoatrophy became prominent. Insulin receptor studies ruled out insulin resistant diabetes type A and B. At this point, we diagnosed this patient as having lipoatrophic diabetes, which is a syndrome characterized by insulin resistant diabetes, acanthosis nigricans, generalized lipoatrophy, and other metabolic disturbances. The control of her diabetes has been poor, and diabetic neuropathy and lipoatrophy-induced painful skin lesions such as clavus and tylosis have been persistent. The present case indicates the importance of careful skin examinations in the diagnosis of this syndrome. PMID- 1607490 TI - Mucha-Habermann disease in a child: possible association with measles vaccination. AB - A 2.5-year-old boy presented with skin lesions consistent with Mucha-Habermann disease, which appeared about 5 days after an injection of freeze-dried live attenuated measles vaccine. He responded to both oral and topical corticosteroid therapy. To my knowledge, this represents the first such association of Mucha Habermann disease with virus vaccination. PMID- 1607491 TI - Reticulate acropigmentation of Kitamura: a case report. AB - A Turkish female patient from Eastern Anatolia is described with the clinical and histopathological features of reticulate acropigmentation of Kitamura (RAK). The brother of the patient, who has similar clinical features, refuses to give a biopsy specimen. No similar lesions are noted on the other members of the patient's family. We have found the case worthwhile to report, since case reports on RAK from ethnic groups other than Japanese are still rare at present. PMID- 1607492 TI - Detection of hexanol dehydrogenase activity in the epidermis of a patient with Sjogren-Larsson syndrome. PMID- 1607493 TI - Priorities in allocating nursing resources. PMID- 1607494 TI - European cities share the challenge of HIV/AIDS. PMID- 1607495 TI - The experience of receiving therapeutic touch. AB - The purpose of this qualitative study was to describe the patient's experience of receiving therapeutic touch (TT) treatments. The design was informed by phenomenology in the sense that it was searching for a definition of the lived experience of the phenomenon of TT. Data were obtained through one open-ended interview and a second clarifying interview of each subject. All data were subjected to content analysis. For participants, the lived experience of TT was described as a linear process that began with the perceived need for and decision to seek treatment. It progressed through one or more treatments and continued to have an impact upon the participants' lives. These findings were examined within the context of Martha Rogers' conceptual system. This study has shown that, for 20 participants receiving treatment, TT was a fulfilling multidimensional experience that facilitated personal growth. Such as experience can only enrich the lives of those who receive treatment. Certainly, a nursing intervention that can achieve such a positive influence has potential for use in all areas of nursing care and needs to be explored further. PMID- 1607496 TI - Validation therapy: extracts from 20 groups with dementia sufferers. AB - Validation therapy, an interactive and group technique for people with dementia, is described. Excerpts from the transcripts of 20 validation therapy groups are presented. These demonstrate the surprising ability of the group members (all moderately demented) to share feelings and problems, follow a theme and utilize facilitating skills in the group setting. The contrast between the group members' behaviour outside the group and that in the group is discussed and future research is proposed. The authors conclude that such groups constitute an exciting new therapy for those with dementia. PMID- 1607497 TI - The care of patients undergoing surgery for gynaecological cancer: the need for information, emotional support and counselling. AB - This study was undertaken by interviewing 105 patients who had undergone major gynaecological surgery for carcinoma of the cervix or vulva in the previous 5 years. A high proportion of the women was still found to be depressed and anxious when interviewed and the majority reported chronic sexual problems. The women were asked if they had received enough information regarding their illness and its treatment, and a high proportion would have liked to have had more information on the after-effects of the operation, including physical, sexual and emotional aspects. Many of the younger women would have liked their partner to have been included in the discussions and 25% of the 40 partners who responded to the questionnaire would have liked more information on the illness and its treatment. The women also indicated their needs for emotional support, discussion and counselling. PMID- 1607498 TI - Plasma exchange therapy reduces the nursing care needed in Guillain-Barre syndrome. AB - The authors compared the effect of plasma exchange therapy on the need for nursing care for 26 patients with acute idiopathic Guillain-Barre syndrome. The patients were randomized either to a plasma exchange (PE) or conservative treatment group. The need for nursing care and the need for specialist nursing services was assessed daily by the nurses at the Department of Neurology. At first, the average need for care was the same for the two groups of patients, but the pattern of care over time was different, with the PE group needing more care at the beginning and then very much less care, whilst the conservative group needed a more uniform amount of care over the entire stay at hospital. In the PE group the need for specialist nursing services increased markedly, and the need for nursing care decreased rapidly after the first 2 weeks to a level lower than that needed by control group patients, probably because PE increased muscle forces of patients. This study suggests that PE treatment is useful in reducing patients' needs for nursing care, especially after the first 2 weeks following the treatment. PMID- 1607499 TI - Nurses' attitudes and satisfaction in two psychogeriatric wards: their structure and correlates. AB - This study investigated the structure and correlates of previously published job satisfaction and attitude measures for nurses through an analysis of responses from staff working in two psychogeriatric wards. A number of inter-correlations were found between the attitude and satisfaction scales. Factor analysis revealed that one of the attitude scales was multi-dimensional and it is suggested that future research should not assume the uni-dimensionality of attitude and satisfaction constructs. It is concluded that psychometric research has important limitations, that a multiplicity of research strategies (both quantitative and qualitative) should be employed in future investigations and that more importance should be accorded to the organizational context of job satisfaction. PMID- 1607500 TI - Learning from experience in the community: an ethnographic study of district nurse students. AB - This study seeks to gain an understanding of the learning experiences of district nurse students in the learning environment of the community, and to examine learning in the practice setting from the perspective of the student. Since the research depends upon the changing and differing interpretations of the individuals involved in the natural setting of the community, an ethnographic approach has been adopted. The experiences of students are monitored throughout the taught practice element of the district nurse course in both inner city and rural/urban locations. Data, collected through interview and observations, are analysed in the context of theory relating to adult learning and learning from experience. Three major categories are identified. Examples from these categories are identified and discussed. The categories are sequential and represent the learning process experienced by the students in the practice setting as they learn to fit into a new environment, test out their own ideas and compare the unreality of college with the reality of practice. Attention is drawn to the difficulties for students of fitting into new settings and trying out change, to the detrimental effect on learning of rigid practice routines and to the powerlessness of community practice teachers to exert a major influence on the learning environment. These issues are discussed in the context of changes in nurse education and evaluation of the community learning environment. PMID- 1607501 TI - The Work Environment Scale: a comparison of British and North American nurses. AB - Previous research into stress in nursing has identified different sources of stress for different specialties without specifying the source of that stress or providing comprehensive understanding of the variables that might contribute to it. This study examines the work environment of 209 nursing staff using the Work Environment Scale. Significant differences were found between a UK sample and the original American norms. Further research highlighted significant interactional effects between demographic variables and the subscales of the WES, and these may form the basis for future research. PMID- 1607502 TI - Effects of communication with important social referents on beliefs and intentions to use condoms. AB - Data from a 1989 survey using the condom attitude and belief instrument with 310 clients from two sexually transmitted disease clinics identified significant social referents who influence condom-use intentions. They are sexual partner, father and friends. The present study found that communication with these referents had a positive net effect on beliefs about and intentions to use condoms. Implications applicable for intervention programmes to increase condom use are to promote talking about condoms between the sexual partners and important social referents and to develop such communication skills. PMID- 1607503 TI - Job satisfaction of nursing staff working in hospitals. AB - Job satisfaction remains an important consideration for both employer and employee and, despite numerous investigations, many questions about it remain unanswered. Many research methodologies have been used with varying degrees of success. However, the trend is now away from simple correlational studies towards modelling techniques. Data from 221 female nurses working full-time in hospitals were collected using questionnaires delivered with monthly salary cheques. The model presented had many statistically significant path coefficients including (in order of size): benefits, participation in decision making, education, routine, promotion, and opportunity for advancement outside their institution. The level of salary was not found to be a statistically significant factor in determining job satisfaction. PMID- 1607504 TI - Measuring the professional self-concept of nurses: a critical review. AB - Nursing literature strongly suggests that the self-concept of nurses is an important concept for academics, administrators and clinicians to consider in the development of the profession. Many valuable research projects have added to the data base on the subject, yet there still remain some questions to be answered. This paper explores the notion of self-concept as it relates to the professional working in nursing. In particular, the paper examines nursing research relating to the professional self-concept of nursing, arguing that the 'professional' self concept of nurses is unique and different from that of the self-concept (while inextricably linked); and that there is room for a new instrument which measures the dimensions of the professional self-concept of nurses. Suggestions for future research include replication and further validation and reliability studies of a new instrument; a cross-cultural study using samples from different countries; testing with various samples from different branches of nursing and further exploring the differences between self-concept and professional self-concept. PMID- 1607505 TI - The poverty of professionalization: a critical analysis of strategies for the occupational advancement of nursing. AB - The purpose of this paper is to evaluate critically the strategies of occupational advancement used by nurses. It is noted that these are frequently framed within the paradigm of professionalization. However, despite the ubiquity of its use, it is argued that this model is inappropriate. Specific strategies are examined. Attempts to appropriate the title of profession by demonstrating that nursing possesses the relevant attributes are dismissed as rhetorical exercises. The rise of managerialism, despite being cloaked in the guise of professionalism, is seen as anti-professional because it restricts the autonomy of individual practitioners. Clinical 'professionalization' is also regarded as problematic because it does not fit with the definition of a professional as an autonomous practitioner. Examination of patient advocacy, and of attempts to validate nursing diagnosis, demonstrate that the occupational advancement of clinical nurses is increasingly dependent upon the co-operation of health care consumers. This dependence is incompatible with the prescriptive powers and exclusive knowledge that are claimed by traditional professions. It is concluded that nurses should abandon the ideology of professionalization and concentrate on the more pertinent issue of maximizing the efficacy of the occupation. PMID- 1607506 TI - Problem-based learning in nurse education: an Australian view. AB - This paper addresses the need to adopt teaching-learning approaches in nursing education that develop links between theory and clinical practice in a meaningful way. Problem-based learning (PBL) is such an approach and is gaining popularity in tertiary nursing programmes in Australia. PBL, as an example of the constructivist philosophy, focuses on students' existing knowledge as a starting point for conceptual change teaching. The implications for the nurse educator's role when using PBL are discussed in terms of assumptions about the nature of teaching and learning; conceptual change teaching; ability to focus; the role of negotiation; and the ability to analyse student learning. These factors are seen to be critical components of the pedagogy necessary for nurse educators to utilize PBL approaches effectively. PMID- 1607507 TI - Greipp's model of ethical decision making. AB - Nurses need to become more aware of everyday ethical decisions and the many factors which influence them in order to develop skills in this cognitive process. This author's model of ethical decision making has been designed and developed to illustrate an overall conception of the interaction between nurse and client within an ethical framework. This model lends itself to the examination of all factors which enter into the ethical decision making process: descriptive, normative and meta-ethics. PMID- 1607508 TI - A preliminary description of the United Kingdom community psychiatric nursing literature, 1960-1990. AB - Five hundred and two items about community psychiatric nursing have been located and classified. The data indicate a continuing rising trend in the number of publications on this subject. The majority of the literature is about the clinical role of the community psychiatric nurse (CPN) and is descriptive/analytical in nature. The second largest proportion is research, the third largest topic is management and administration and the fourth largest is CPN education. The amount of 'clinical' literature as a proportion of the whole has been in decline since the mid-1970s. The majority of papers cannot be classified by the specialism of community psychiatric nursing to which they relate, but a small and significant number have been written about the care of the elderly mentally ill. Overall, the practising CPNs have been the most prolific writers, followed by academic nurses and then nurse managers. Contributions from other professions are miniscule. Over recent years the contribution of nurse managers has declined, and that of academic nurses has risen. The contribution of practising CPNs remains robust. Research publications also continue to rise, the majority being produced by academics, but large contributions are also being made by nurse managers and practising CPNs. In the early years nearly all publications of articles were in populist nursing magazines. In recent years the spread of journals in which items about community psychiatric nursing appear has widened considerably. PMID- 1607509 TI - The use of the first person in academic writing: objectivity, language and gatekeeping. AB - Researchers have experienced difficulties in having papers which are based on qualitative research accepted for publication because the papers have been written in the first person. Arguments are presented to show why the use of the neutral, anonymous third person is deceptive when applied to quantitative research because it obliterates the social elements of the research process. With regard to research in the qualitative, critical and feminist paradigms, it is further argued that the use of the first person is required in keeping with the epistemologies of the research and in the pursuit of reflexivity. Links are made between these arguments and the process of reviewing for academic journals. Conclusions are drawn in favour of the use of the first person, where this is appropriate to the mode of research reported and where an author is giving a personal judgement arrived at on the basis of reasonable evidence. In keeping with this position, this paper is written in the first person. PMID- 1607510 TI - Ergonovine maleate testing during cardiac catheterization: a 10-year perspective in 3,447 patients without significant coronary artery disease or Prinzmetal's variant angina. AB - The utility of ergonovine testing for coronary artery spasm was assessed in 3,447 patients with angiographically insignificant (less than 50% diameter stenosis) or no coronary artery disease. No patients clinically had Prinzmetal's variant angina. Overall, 4% had a positive ergonovine test result, defined by spasm causing greater than or equal to 75% focal stenosis. Complications related to ergonovine use occurred in 11 patients (0.03%). In a training sample of 1,136 patients (studied between 1980 and 1984), two independent predictors of spasm were found by using multivariate analysis: the amount of visible coronary artery disease on the coronary angiogram (p less than 0.0001) and a smoking history (p = 0.001). A model to predict spasm based on these variables was validated in a test group of 2,311 patients who received ergonovine from 1985 to 1989. This model allowed the identification of a subset of 400 patients in the validation sample who had a 10% positive test rate compared with a 2% positive test rate in the remaining patients. These results should permit clinicians who use provocative testing in the catheterization laboratory to reserve testing for the subset of this group of patients most likely to have abnormal findings. PMID- 1607511 TI - Estimation of left ventricular end-diastolic pressure from Doppler transmitral flow velocity in cardiac patients independent of systolic performance. AB - In patients with heart disease, changes in left ventricular filling pressures produce alterations in the Doppler transmitral flow velocity and isovolumetric relaxation time. This investigation explored the hypothesis that combining isovolumetric relaxation time with measurements derived from the transmitral flow velocity can be used to estimate left ventricular end-diastolic pressure. Simultaneous Doppler and left ventricular pressure recordings were obtained in 33 patients (24 men with a mean age of 58 +/- 11 years) and an ejection fraction ranging from 15% to 74% (mean 55 +/- 15%). The following Doppler measurements correlated significantly with left ventricular end-diastolic pressure (range 4 to 36 mm Hg): isovolumetric relaxation time (IVRT; r = -0.73), atrial filling fraction (AFF; r = -0.66), deceleration time (DT; r = -0.59), ratio of early transmitral flow velocity to atrial flow velocity (E/A ratio; r = -0.53) and time from termination of mitral flow to the electrocardiographic R wave (MAR; r = 0.37). Combining these measurements into a multilinear regression equation provided a more accurate estimate of end-diastolic pressure (LVEDP; r = 0.80; SEE = 7.4). The equation LVEDP = 46 -0.22 IVRT -0.10 AFF -0.03 DT -(2 divided by E/A) + 0.05 MAR was tested prospectively in 26 additional patients (mean age 55 +/- 11 years; ejection fraction 41 +/- 23%) with simultaneous Doppler and hemodynamic recordings but with the two measurements made independently, in blinded fashion, by additional observers. Estimated and measured end-diastolic pressures correlated well with each other (r = 0.86).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607512 TI - Anaerobic metabolism as an indicator of aerobic function during exercise in cardiac patients. AB - To determine whether patients with heart disease depend more than normal subjects on anaerobic metabolism to perform the same level of exercise, the anaerobic threshold, slope of the increase in carbon dioxide output with respect to oxygen uptake (delta VCO2/delta VO2) and the slope of the increase in oxygen uptake with respect to the increase in work rate (delta VO2/delta WR) both below and above the anaerobic threshold during exercise were evaluated. A total of 106 patients with chronic heart disease and 42 healthy subjects performed a symptom-limited incremental exercise test in a ramp pattern on a cycle ergometer. Peak oxygen uptake was significantly lower in the patients with heart disease than in the normal subjects. The anaerobic threshold, which was 20 +/- 4.6 ml/min per kg in normal subjects, decreased significantly with progressing severity of functional class: 16 +/- 2.4, 14.1 +/- 2.5 and 11.3 +/- 1.5 ml/min per kg, respectively, in patients in class I, class II and class III. The slope of delta VO2/delta WR, which represents the degree of aerobic metabolism, was also decreased both below and above the anaerobic threshold with increasing severity of heart disease. delta VCO2/delta VO2 below the anaerobic threshold was approximately 0.9 (p = NS between normal subjects and patients). However, delta VCO2/delta VO2 above the anaerobic threshold became steeper with increasing severity of heart disease: 1.37 +/- 0.17 in normal subjects versus 1.55 +/- 0.24, 1.67 +/- 0.3 and 1.8 +/- 0.35 respectively, in patients in functional class I, class II and class III.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607513 TI - Frequency versus time domain analysis of signal-averaged electrocardiograms. I. Reproducibility of the results. AB - Three repeated signal-averaged electrocardiographic (ECG) recordings were made in 40 subjects (15 healthy volunteers, 10 patients with ventricular tachycardia without apparent heart disease and 15 patients with ventricular tachycardia after myocardial infarction). In each subject, the three recordings were made within 25 min. The recordings were subsequently analyzed by 1) the conventional time domain method of signal-averaged ECG analysis with use of filter settings of 25 to 250 Hz and 40 to 250 Hz, 2) a spectral analysis method computing the energy area within the spectral boundaries of 40 to 140 Hz and the ratio between the energies of areas within the boundaries 40 to 140 Hz and 0 to 40 Hz, and 3) spectral temporal mapping computing the "normality factor." The study compared the reproducibility of these three approaches to the analysis of signal-averaged ECGs. First, the reproducibility of the diagnostic conclusions (that is, of the diagnosis of late potentials) was compared for the time domain method and for spectral temporal mapping. Second, the reproducibility of the numeric values of individual indexes provided by different methods was compared for all methods by computing the ratios between standard deviations of measurements in individual patients and standard deviation of all measurements. The reproducibility of diagnostic conclusions was significantly higher for the time domain method than for spectral temporal mapping (p less than 0.05, sign test). The numeric reproducibility of the normality factors produced by spectral temporal mapping was significantly lower than the numeric reproducibility of the values of all indexes provided by time domain, spectral area and spectral area ratio methods (p less than 0.05 to 0.00005, Wilcoxon tests). Spectral temporal mapping was the least reproducible method for the analysis of signal-averaged ECGs. PMID- 1607514 TI - Frequency versus time domain analysis of signal-averaged electrocardiograms. II. Identification of patients with ventricular tachycardia after myocardial infarction. AB - Late potentials detected by the time domain signal-averaged electrocardiogram (ECG) are a well established marker for ventricular tachycardia in patients after a myocardial infarction, but the value of frequency domain analysis of the signal averaged ECG in identifying these patients remains controversial. This study compared the results of time domain, frequency domain and spectral temporal mapping analyses of the signal-averaged ECG in 30 postinfarction patients with spontaneous sustained ventricular tachycardia and in 30 postinfarction patients without ventricular tachycardia matched for age, gender and infarct site. No patient with bundle branch block was included. Time domain signal-averaged ECG indexes were significantly different in patients with and without ventricular tachycardia (p less than 0.001). Frequency domain results were not consistently different between these groups. The values of the normality factor of spectral temporal mapping were significantly lower in patients with ventricular tachycardia (p less than 0.04). Results of the time domain signal-averaged ECG were abnormal in 22 patients with ventricular tachycardia (73%) but in only 3 control patients (10%) (p less than 0.001). Spectral temporal mapping results were abnormal in 21 patients with ventricular tachycardia (70%) compared with 12 control patients (40%) (p less than 0.04). When the optimal numeric values of dichotomy points were computed for patient stratification at different sensitivity levels, time domain analysis identified patients with ventricular tachycardia with significantly fewer false positive results than were obtained with either frequency analysis or spectral temporal mapping. It is concluded that frequency domain analysis and spectral temporal mapping of the signal-averaged ECG did not improve the identification of postinfarction patients with ventricular tachycardia and without bundle branch block. PMID- 1607515 TI - Frequency versus time domain analysis of signal-averaged electrocardiograms. III. Stratification of postinfarction patients for arrhythmic events. AB - The predictive characteristics of spectral temporal analysis and time domain analysis of the signal-averaged electrocardiogram (ECG) for postinfarction arrhythmic events were compared in 257 patients. During a 6-month follow-up period, 7 patients (2.7%) died suddenly and 9 (3.5%) developed spontaneous sustained ventricular tachycardia. The mean numeric values of the standard time domain signal-averaged ECG variables in patients without arrhythmic events differed significantly from those in patients with arrhythmic events. The mean values of the spectral temporal signal-averaged ECG variables did not differ between the two patient groups. A strategy requiring positivity in any two time domain signal-averaged ECG variables provided the optimal receiver operating characteristic curves for predicting arrhythmic events. With spectral temporal analysis, a strategy using the Hanning window and diagnosing a positive signal averaged ECG when two variables were abnormal provided the optimal curve for predicting arrhythmic events. Receiver operating characteristic curves showed that over a wide range of sensitivity, time domain variables had higher specificity for predicting arrhythmic events than did spectral temporal variables. Time domain analysis also provided significantly fewer false positive results than did spectral temporal analysis up to sensitivity values of 70%. It is concluded that time domain analysis of the signal-averaged ECG is superior to spectral temporal analysis for predicting arrhythmic events after myocardial infarction. PMID- 1607516 TI - Tweaking the signal-averaged electrocardiogram in search of improved predictive accuracy. PMID- 1607517 TI - In vitro high resolution intravascular imaging in muscular and elastic arteries. AB - High resolution (125-microns lateral, 55-microns axial) images of 16 muscular (femoral) and 15 elastic (common carotid) human arteries were made in vitro with use of a prototype 45-MHz intravascular imaging system. Four distinct regions of scattering, excluding plaque, were identified in the ultrasound images corresponding histologically to the adventitia, media, thickened intima and elastic laminae, both internal and external. Arterial samples imaged under pressure and in a collapsed state underwent dimensional changes but exhibited similar levels of backscatter amplitude. All the elastic arteries displayed a prominent echogenic media, whereas all the muscular arteries displayed an echolucent media. Scattering from the internal elastic lamina in muscular arteries provided an excellent landmark for defining the location and extent of intimal thickening or plaque. In elastic arteries the internal elastic lamina could not be distinguished from the echogenic media; consequently, the boundary between the media and intimal layer was indistinct. Differences in the relative concentration and organization of collagen and elastin were found to provide a consistent explanation for the differences in scattering that were observed between individual layers within an artery as well as between muscular and elastic arteries. PMID- 1607518 TI - Metabolic evidence of viable myocardium in regions with reduced wall thickness and absent wall thickening in patients with chronic ischemic left ventricular dysfunction. AB - Reduced end-diastolic wall thickness with absent systolic wall thickening has been reported to represent nonviable myocardium in patients with chronic coronary artery disease. To assess whether reduced regional end-diastolic wall thickness and absent wall thickening accurately identify nonviable myocardium, 25 patients with ischemic left ventricular dysfunction (ejection fraction at rest 27 +/- 10%) underwent positron emission tomography with oxygen-15-labeled water and 18fluorodeoxyglucose to assess metabolic activity and spin-echo gated nuclear magnetic resonance imaging to measure regional end-diastolic wall thickness and wall thickening. The presence of metabolic activity was defined as 18fluorodeoxyglucose uptake (corrected for partial volume) greater than 50% of that in normal regions. Of 355 myocardial regions evaluated, 266 were hypokinetic or normokinetic at rest and 89 were akinetic (that is, absent wall thickening). 18Fluorodeoxyglucose uptake was observed in 97% of the hypokinetic and normokinetic regions and in 74% of the akinetic regions. End-diastolic wall thickness was greater in akinetic regions with than in those without 18fluorodeoxyglucose uptake (11 +/- 4 vs. 7 +/- 3 mm, p less than 0.01). The highest values for sensitivity and specificity of end-diastolic wall thickness in predicting the absence of metabolic activity in akinetic regions were 74% and 79%, respectively, and corresponded to an end-diastolic threshold of 8 mm. However, the positive predictive accuracy was only 55% and did not improve for other end-diastolic wall thickness values. In all myocardial regions, there was only a weak correlation between 18fluorodeoxyglucose activity and either end diastolic wall thickness (r = 0.17) or wall thickening (r = 0.32). Thus, metabolic activity is present in many regions with reduced end-diastolic wall thickness and absent wall thickening. These data indicate that assessment of regional anatomy and function may be inaccurate in distinguishing asynergic but viable myocardium from nonviable myocardium. PMID- 1607519 TI - Intermediate-term outcome after pulmonary balloon valvuloplasty: comparison with a matched surgical control group. AB - To assess late (4 to 5 years) gradient reduction after pulmonary balloon valvuloplasty in childhood, and to compare the effectiveness of valvuloplasty with that of surgical valvotomy, 20 valvuloplasty-treated children and their age- and gradient-matched surgical control patients underwent prospective, noninvasive evaluation. The average age at intervention was 4.3 +/- 1 years for the valvuloplasty group versus 4.7 +/- 0.8 years for the surgical control group (p = NS). Before intervention the peak systolic pulmonary stenosis gradient was 76 +/- 5 and 74 +/- 4.4 mm Hg for the valvuloplasty and surgery groups, respectively (p = NS). Late evaluation consisted of clinical examination, two-dimensional echocardiogram and Doppler study, 24-hour Holter monitoring, 12-lead electrocardiogram, exercise treadmill study and chest radiograph performed an average of 5.3 +/- 0.3 years after valvuloplasty and 11.7 +/- 0.5 years after surgery (p less than 0.01). The patients treated with balloon valvuloplasty had no evidence of restenosis; the residual pulmonary stenosis gradient at follow-up was 24 +/- 2.7 mm Hg (range 8 to 48) versus 35 +/- 3.6 mm Hg (range 19 to 70) immediately after valvuloplasty (p = NS). Comparison of the late residual gradients between treatment groups showed no hemodynamically significant difference (24 +/- 2.7 versus 16 +/- 1.5 mm Hg, balloon versus surgery; p less than 0.01). However, there was, a significant difference in the degree and severity of pulmonary valve insufficiency and ventricular ectopic activity between groups. In the balloon valvuloplasty group 11 patients had no pulmonary insufficiency, and the remaining 9 had mild insufficiency.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607520 TI - Randomized angiographic trial of recombinant tissue-type plasminogen activator (alteplase) in myocardial infarction. RAAMI Study Investigators. AB - Clot dissolution with restoration of infarct-related artery blood flow is the likely mechanism for the improved prognosis and mortality reduction seen after thrombolytic therapy of acute myocardial infarction. A pilot study has suggested that 100 mg of recombinant tissue-type plasminogen activator (rt-PA) infused over 90 min may lead to higher patency rates than the current standard of 100 mg over 3 h. In this multicenter, randomized, open label trial, 281 patients with acute myocardial infarction receive 100 mg of rt-PA according to either the standard 3 h infusion regimen (an initial 10-mg bolus followed by 50 mg for the 1st h, then 20 mg/h for 2 h) or an accelerated 90-min regimen (15-mg bolus followed by 50 mg over 30 min, then 35 mg over 60 min). All patients also received intravenous heparin and oral aspirin during and after rt-PA infusion. At 60 min after initiation of the rt-PA infusion, the observed angiographic patency rates were 76% (95% confidence intervals 65% to 84%) in the accelerated regimen group and 63% in the control group (52% to 73%, p = 0.03). At 90 min these rates were 81% (73% to 87%) and 77% (68% to 84%), respectively (p = 0.21). Both randomized groups experienced similar rates of recurrent ischemia, reinfarction, angiographic reocclusion, other complications of myocardial infarction (including stroke and death) and bleeding complications.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607521 TI - Pulmonary valve insufficiency: malignant or benign? PMID- 1607522 TI - Surgical management of the infant with coarctation of the aorta and ventricular septal defect. AB - Clinical and cardiac catheterization data were collected from 39 infants with coarctation of the aorta and ventricular septal defect, 31 of whom were initially managed only by surgical repair of coarctation. Data were analyzed to determine mortality, morbidity, outcome and factors that might predict survival or the need for septal defect closure. Of the eight patients who did not require surgical treatment before 3 months of age, seven underwent coarctation repair alone at a mean age of 2.3 years. Of the 23 infants managed with coarctation repair alone, before age 3 months, 9 needed no additional surgical treatment and 6 required early and 8 required late repair of the ventricular septal defect. Seven infants underwent coarctation repair and simultaneous pulmonary artery banding and one eventually required debanding after spontaneous closure of the septal defect. The overall mortality rate in this series was 10.3% (mean follow-up time 5.7 years). Of 39 infants, 16 (41%) never required a second operation for ventricular septal defect closure. For patients who had only coarctation or coarctation repair with pulmonary artery banding at less than 3 months of age, ventricular septal defect size was categorized as small (less than 0.5 cm/m2), moderate (less than 1 cm/m2) or large (greater than 1 cm/m2) on the basis of defect size at operative repair or echocardiographic or angiographic assessment. Defect size did not necessarily correlate with the need for operative repair.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607523 TI - Imaging of pulmonary venous pathway obstruction in patients after the modified Fontan procedure. AB - To evaluate the efficacy of chest roentgenograms and echocardiograms in identifying pulmonary venous pathway obstruction in patients after the modified Fontan procedure, the records of 297 patients who underwent 307 Fontan procedures between 1984 and 1990 were reviewed. Twelve cases of pulmonary venous pathway obstruction documented by autopsy (3 cases) or cardiac catheterization (9 cases with an A wave gradient greater than or equal to 4 mm Hg) were found in 10 patients (mean age 43 +/- 28 months). The mechanisms of obstruction included narrow pulmonary vein ostia in six cases, narrow left atrial outlet in four and atrial baffle obstruction in three. Two causes of obstruction were present in one case. No patient had pulmonary venous congestion on chest roentgenograms. Pathway diameters indexed to 3 square root of body surface area with two-dimensional echocardiography were found to be 6.8 +/- 1.2 mm/3 square root of m2 in the subcostal frontal view, 7.9 +/- 0.6 mm/3 square root of m2 in the subcostal sagittal view and 6.5 +/- 1.7 mm/3 square root of m2 in the apical "four-chamber" view. These values differed significantly from those in 11 age-matched patients undergoing the Fontan procedure without pulmonary venous pathway obstruction documented by catheterization (p = 0.001). With pulsed Doppler ultrasound, there was a relatively narrow range of velocities distal to the obstruction (1.3 to 2.5 m/s). In five of the seven cases with pulsed Doppler measurements, flow was continuous and the Doppler spectral recordings were not phasic. Thus, in patients who have undergone the Fontan procedure and have pulmonary venous pathway obstruction 1) chest roentgenography cannot be used as a screening tool; 2) distal velocities as low as 1.3 m/s occur, usually with nonphasic, continuous forward flow; and 3) pathway diameters indexed to 3 square root of body surface area may be used as an output-independent parameter to cross-check Doppler data. PMID- 1607524 TI - Repair of conotruncal abnormalities with the use of the valved conduit: improved early and midterm results with the cryopreserved homograft. AB - Repair of complex cardiac lesions has been facilitated by the availability of valved conduits to reestablish right ventricular to pulmonary artery continuity. From 1977 to June 1991, 148 patients underwent repair with insertion of a conduit. Their mean age was 6.6 years (11 days to 45 years). The diagnosis was transposition of the great arteries with ventricular septal defect and left ventricular outflow tract obstruction in 51, truncus arteriosus in 36, pulmonary atresia with ventricular septal defect in 25, tetralogy of Fallot in 19, double outlet right ventricle in 10, pulmonary atresia with intact ventricular septum in 6 and atrioventricular canal with pulmonary atresia in 1. A Dacron porcine-valved conduit was used in 37, a homograft conduit in 106 and a nonvalved conduit in 5. There were 13 early deaths overall (8.8%); 8 (22%) of the early deaths occurred in the 37 patients who received a Dacron graft, 4 (3.8%) occurred in the 106 patients who received a homograft and 1 occurred in a patient with a nonvalved Gore-Tex conduit. An additional patient underwent orthotopic heart transplantation in the early postoperative period. In 117 patients operated on from January 1985 to June 1991 the early mortality rate was 2.6% (3 of 117). Among 28 patients receiving a Dacron porcine-valved graft there were two late deaths (7.1%) after a mean follow-up interval of 93 months, and 8 patients required reoperation for conduit obstruction. Among 102 homograft recipients there were two late deaths (1.9%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607525 TI - Ambulatory blood pressure monitoring and left ventricular mass and function after successful surgical repair of coarctation of the aorta. AB - Late cardiovascular morbidity and mortality remain significant despite apparently successful surgical repair of aortic coarctation. Alterations in cardiac function have been reported in normotensive patients who have had successful repair, the reasons for which remain unclear. This study addresses the relation between ambulatory blood pressure measurements and alterations in left ventricular performance in 20 patients with normotension at rest after successful repair of aortic coarctation. Exercise testing, ambulatory blood pressure monitoring and two-dimensional echocardiographic studies in 13 boys and 7 girls (mean age 14.2 +/- 2.31 and 14.7 +/- 3 years, respectively) who had no evidence of recoarctation were compared with the findings in 20 matched control subjects. No difference was found in systolic blood pressure at rest or peak exercise between patients and control subjects. Male patients developed a significant arm/leg gradient at peak exercise. Systolic ambulatory blood pressure was higher throughout the day in the male group. In the female group, systolic blood pressure was higher only during sleep. No difference was found in diastolic blood pressure or heart rate. The transverse aortic arch was smaller and the left ventricular mass greater in all patients. The relation of wall stress to rate-corrected velocity of shortening was 2 SD above normal in 8 of the 20 patients, suggesting that some have enhanced contractility. The E/A ratio on the atrial echocardiogram was significantly reduced in the patient group. Successfully treated patients who are normotensive at rest after operation are still at risk for developing end organ damage, which is probably explained by incipient mild hypertension documented by ambulatory blood pressure monitoring. PMID- 1607526 TI - Transcatheter closure of coronary artery fistulas. AB - Transcatheter closure of a coronary artery fistula was undertaken in nine patients. There were three fistulas from the left circumflex coronary artery to the coronary sinus, three from the left anterior descending coronary artery to the right ventricular apex, two from the right coronary artery to the superior vena cava/right atrial junction and one fistula from the left circumflex artery to the pulmonary artery. The fistula was closed with Gianturco coils in six patients, a double-umbrella device in two and a combination of an umbrella and coils in one patient. All fistulas are completely occluded. Complications consisted of migration of two coils, one of which was retrieved, and a transient junctional tachycardia in one patient. In an additional three patients with multiple coronary artery fistulas, transcatheter occlusion was not attempted. PMID- 1607527 TI - Determination of patch electrode position for the internal cardioverter defibrillator by cine computed tomography and its relation to the defibrillation threshold. AB - Cardioverter-defibrillator implantation in 22 consecutive patients after aborted sudden cardiac death was followed by prospective determination of the correct anatomic position of epicardial patch electrodes by chest X-ray study and cine computed tomography; the data were compared with the defibrillation threshold obtained intraoperatively. Patch electrode position was qualitatively graded. Computed tomography improved the assessment as compared with X-ray study in 13 patients (59%), visualizing electrodes in relation to the underlying myocardial and vascular structures. Although the computed tomographic technique provided more precise visualization, its grading of patch position correlated as poorly as that of the X-ray study with the measured acute defibrillation threshold. Three dimensional reconstruction by computed tomography made it possible to determine quantitatively left ventricular mass (free wall and septum) and the mass encompassed by the patch electrodes. The 34.6 +/- 13.7% (range 12.6 to 61.1%) of the left ventricular mass encompassed by both patch electrodes showed a linear relation to the defibrillation threshold (r = 0.64, p = 0.01). Differentiation of free wall and septal mass in these measurements revealed that the proportion of septal mass encompassed by patch electrodes correlated closely with the defibrillation threshold (r = -0.6, p = 0.019), whereas that of the free wall mass, although significantly larger (35.4 +/- 15.8 vs. 20.6 +/- 15.4 g, p = 0.007), did not. Thus, the position of epicardial patch electrodes could be reliably determined by computed tomography.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607528 TI - Recombinant tissue-type plasminogen activator ameliorates ischemic derangements induced by thrombotic occlusion in closed chest anesthetized dogs. AB - Effects of thrombotic coronary occlusion followed by thrombolytic reperfusion with recombinant tissue-type plasminogen activator (rt-PA) on infarct size and left ventricular function were studied in anesthetized closed chest dogs. After thrombotic occlusion of the left anterior descending coronary artery was produced by a copper coil technique, 74 dogs were randomly alloted to three groups; dogs treated with rt-PA at 90 min (n = 23) (group I) and at 180 min (n = 25) (group II) of the thrombotic occlusion, and 26 dogs treated with saline solution (permanent thrombotic occlusion, group III). The loading dose of intravenous rt PA was 8,160 IU/kg body weight per min at the initial 60 min and the maintenance dose was 2,450 IU/kg per min continuously infused for 24 h. Thrombolytic recanalization was achieved at 15 +/- 4 and 18 +/- 6 min after rt-PA infusion in groups I and II, respectively. Infarct size and area at risk were determined by triphenyltetrazolium chloride staining and postmortem angiography; infarct size/area at risk ratio was 10 +/- 3% (n = 10), 33 +/- 7% (n = 9) and 63 +/- 3% (n = 10) in groups I, II and III, respectively (difference significant among groups). To examine whether infarct size and left ventricular function after thrombolytic reperfusion differ from those after mechanical reperfusion, 39 other dogs (group IV) underwent mechanical coronary occlusion for 106 +/- 1 min (occlusion period comparable with that of group I) and reperfusion using a balloon catheter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607529 TI - Recombinant tissue-type plasminogen activator: an infarct-sparing effect beyond thrombolysis? PMID- 1607530 TI - Sustained reflow in dogs with coronary thrombosis with K2P, a novel mutant of tissue-plasminogen activator. AB - Coronary artery reocclusion after thrombolysis with human recombinant tissue-type plasminogen activator (rt-PA) is related to the short half-life of this agent in plasma. K2P, a mutant of rt-PA lacking the fibronectin fingerlike, epidermal growth factor-like and first kringle domains (amino acids 6 to 173) and having the glycosylation site Asn184 mutagenized to Gln, has been produced in Chinese hamster ovary cells. In this study we compared the thrombolytic effect of K2P and rt-PA in dogs with electrically induced coronary artery thrombosis. Both agents were given intravenously in equimolar amounts over 20 min after the occlusive thrombus was stable for 30 min; dogs were monitored for 1 h after reperfusion if flow occurred. Coronary blood flow was restored by rt-PA in 6 (60%) of 10 dogs. The restored flow lasted for 49 +/- 12 min and mean flow at 60 min from the start of reperfusion was 7 +/- 3 ml/min. The reocclusion rate was 50% (three of six dogs). Flow was restored in five (100%) of five dogs by K2P. The restored blood flow lasted during the entire 1-h observation period in all but one dog and mean flow at 60 min was 49 +/- 16 ml/min (p less than 0.02 vs. flow in rt-PA-treated dogs). Restored coronary blood flow showed marked cyclic flow variations in rt-PA treated but not in K2P-treated dogs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607531 TI - Reduced cardiac reserve in amiodarone-treated pigs after cardiopulmonary bypass and cardioplegic arrest. AB - An animal model was designed for blinded study to elucidate whether cardiac pump failure after heart surgery in amiodarone-treated patients is due to interference between the drug and the surgical procedures. Seventeen adult pigs were treated with amiodarone for 30 days (study animals, 1,400 mg/day, n = 9; untreated control animals, n = 8) followed by exposure to cardiopulmonary bypass and topical cold cardioplegic arrest (Bretschneiders solution) for 60 min. Apart from 1 g of calcium, no inotropic agents were administered. Cardiac reserve was tested by ventricular pacing (200 beats/min for 30 min or until exhaustion). No difference in hemodynamic status was observed between the treated and the untreated group before pacing. Pacing duration in the amiodarone-treated pigs was 10 +/- 3 versus 22 +/- 4 min in control pigs (p less than 0.05). Only one amiodarone-treated pig survived 30 min of pacing compared with five control pigs (11% vs. 63%, p less than 0.05). The following variables differed significantly in the two groups during pacing: cardiac output, left ventricular pressure, arterial pressure and peak positive and negative first derivative of left ventricular pressure (dP/dt). Most marked were the changes in peak positive dP/dt, indicating a compromised systolic function. The two groups did not differ in preload or afterload at any time during the experiments. PMID- 1607532 TI - Recombinant tissue-type plasminogen activator versus a novel dosing regimen of urokinase in acute pulmonary embolism: a randomized controlled multicenter trial. AB - Thrombolysis of acute pulmonary embolism can be accomplished more rapidly and safely with 100 mg of recombinant human tissue-type plasminogen activator (rt-PA) (Activase) than with a conventional dose of urokinase (Abbokinase) given as a 4,400-U/kg bolus dose, followed by 4,400 U/kg per h for 24 h. To determine the effects of a more concentrated urokinase dose administered over a shorter time course, this trial enrolled 90 patients with baseline perfusion lung scans and angiographically documented pulmonary embolism. They were randomized to receive either 100 mg/2 h of rt-PA or a novel dosing regimen of urokinase: 3 million U/2 h with the initial 1 million U given as a bolus injection over 10 min. Both drugs were delivered through a peripheral vein. To assess efficacy after initiation of therapy, repeat pulmonary angiograms at 2 h were performed in 87 patients and then graded in a blinded manner by a panel of six investigators. Of the 42 patients allocated to rt-PA therapy, 79% showed angiographic improvement at 2 h, compared with 67% of the 45 patients randomized to urokinase therapy (95% confidence interval for the difference in these proportions [rt-PA minus urokinase] is -6.6% to 30.4%; p = 0.11). The mean change in perfusion lung scans between baseline and 24 h was similar for both treatments. Three patients (two treated with rt-PA and one with urokinase) had an intracranial hemorrhage, which was fatal in one. The results indicate that a 2-h regimen of rt-PA and a new dosing regimen of urokinase exhibit similar efficacy and safety for treatment of acute pulmonary embolism. PMID- 1607533 TI - Mitral regurgitation due to ruptured chordae tendineae in patients with hypertrophic obstructive cardiomyopathy. AB - Mitral valve regurgitation in association with hypertrophic obstructive cardiomyopathy is usually caused by the systolic anterior motion of the anterior mitral leaflet. Recently, five patients were encountered with hypertrophic obstructive cardiomyopathy who had mitral regurgitation due to ruptured chordae tendineae. The diagnosis was confirmed in all patients during operation for left ventricular septal myectomy-myotomy (Morrow procedure). Preoperative identification of ruptured chordae tendineae as the cause of mitral regurgitation was established by transesophageal echocardiography in the three most recent cases. All patients had successful septal myectomy-myotomy for relief of left ventricular outflow obstruction, and mitral valve competence was restored by valve repair rather than by prosthetic valve replacement. The clinical course of these patients illustrates important management considerations as well as the utility of transesophageal echocardiography for diagnosis. Chordal rupture should be considered in the differential diagnosis of mitral regurgitation in patients with hypertrophic obstructive cardiomyopathy, especially in those with acute hemodynamic deterioration. PMID- 1607534 TI - Standardization of cardiac tomographic imaging. The Cardiovascular Imaging Committee, American College of Cardiology; The Committee on Advanced Cardiac Imaging and Technology, Council on Clinical Cardiology, American Heart Association; and Board of Directors, Cardiovascular Council, Society of Nuclear Medicine. PMID- 1607535 TI - Heparin-induced prolongation of partial thromboplastin time after thrombolysis: relation to coronary artery patency. HART Investigators. AB - Having previously shown in the Heparin Aspirin Reperfusion Trial that the empiric use of early intravenous heparin after recombinant tissue-type plasminogen activator (rt-PA) is an important component in the overall treatment strategy, we examine in this report the specific relation between the degree of prolongation of activated partial thromboplastin time and coronary artery patency. To evaluate the hypothesis that arterial patency after administration of rt-PA for acute myocardial infarction is sustained by effective anticoagulation, activated partial thromboplastin time of heparin recipients was determined 8 and 12 h after the start of thrombolysis. Mean activated partial thromboplastin time was higher among patients with an open infarct-related artery than in those with a closed artery (81 +/- 4 vs. 54 +/- 9 s, p less than 0.02). Only 45% of patients with values less than 45 s at both 8 and 12 h had Thrombolysis in Myocardial Infarction (TIMI) flow grade 2 or 3 in the infarct-related artery at 18 h. In contrast, 88% of patients with activated partial thromboplastin time greater than 45 s and 95% of those with values greater than 60 s had an open infarct-related artery at 18 h (p = 0.003 and 0.0006, respectively). Among patients with an initially patent infarct-related artery who underwent repeat angiography at 7 days, activated partial thromboplastin time was similar in those with a persistently patent artery and those with late reocclusion. Excessive anticoagulation did not appear to increase hemorrhagic risk except that access site-related hemorrhage was more common in patients with activated partial thromboplastin time greater than 100 s at 8 h.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607536 TI - Antecedent angina pectoris predicts worse outcome after myocardial infarction in patients receiving thrombolytic therapy: experience gleaned from the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. AB - The significance of antecedent angina in predicting clinical outcome was assessed in 8,329 patients with acute myocardial infarction who received thrombolytic therapy with either recombinant tissue-type plasminogen activator or streptokinase. There were 2,370 patients with antecedent angina for greater than 1 month, 1,512 patients with antecedent angina for less than or equal to 1 month and 4,447 patients with no antecedent angina. The longer the duration of angina, the worse the baseline characteristics in the three groups: the mean patient age was 65 versus 62 versus 61 years, respectively (p less than 0.0001); the rate of previous myocardial infarction was 37% versus 18% versus 10% (p less than 0.0001); and the rate of hypertension was 40% versus 31% versus 27% (p less than 0.0001). Antecedent angina was associated with a longer hospital stay (11.3 and 11.7 days vs. 10.8 days, p less than 0.0001), a higher incidence of bypass surgery (2.2% vs. 1.2% vs. 0.7%, p = 0.0001), a worse Killip class at discharge (10.6% of patients in class greater than 1 vs. 8.7% vs. 6.4%, p = 0.0001), and a higher hospital and 6-month mortality (12.1% and 18% vs. 8.9% and 11.6% vs. 6.6% and 9.2%, respectively, p less than 0.0001). A multivariate analysis taking into account all baseline characteristics confirmed the independent association of antecedent angina with mortality, with a relative risk of 1.4 to 1.47 (p less than 0.001). Antecedent angina predicts a worse clinical outcome and a more intense use of medical resources in patients with acute myocardial infarction receiving thrombolytic therapy. PMID- 1607537 TI - Transesophageal Doppler echocardiography in obstructive hypertrophic cardiomyopathy: clarification of pathophysiology and importance in intraoperative decision making. AB - To better understand the pathophysiology of obstruction of left ventricular outflow in hypertrophic cardiomyopathy and to determine the value of intraoperative transesophageal Doppler echocardiography in decision making, 32 consecutive patients undergoing ventriculomyectomy were assessed. The mean preoperative left ventricular outflow gradient was 83 +/- 39 mm Hg and the mean basal septal width was 24 +/- 6 mm. Compared with transesophageal findings in 10 normal control subjects, the mitral leaflets were longer and the coaptation point was abnormal in the patients with obstructive hypertrophic cardiomyopathy (anterior and posterior leaflet lengths in the patients were 31 +/- 4 vs. 22 +/- 3 mm in the control group [p less than 0.00001] and 20 +/- 2 vs. 15 +/- 3 mm in the control group [p less than 0.00001]). The coaptation point in the patient group was in the body of the leaflets at a mean of 9 +/- 2 mm from the anterior leaflet tip, whereas it was at or within 3 mm of the leaflet tip in the normal group. During early systole, the distal third to half of the anterior mitral leaflet angled sharply anteriorly and superiorly (systolic anterior motion), resulting in leaflet-septal contact and incomplete mitral leaflet coaptation in mid-systole. This caused the formation of a funnel, composed of the distal parts of both leaflets, that allowed a jet of posteriorly directed mitral regurgitation to occur in mid- and late systole. The sequence of events in systole was eject/obstruct/leak. Transesophageal echocardiography was also helpful in planning the extent of the resection, assessing the immediate result and excluding important complications. In successful cases, the post-myectomy study showed 1) a dramatic thinning of the septum, with widening of the left ventricular outflow tract to a width similar to that in the normal subjects, 2) resolution of systolic anterior motion and the left ventricular outflow tract color mosaic, and marked reduction or abolition of mitral regurgitation despite persistence of abnormal mitral leaflet length and an abnormal mitral leaflet coaptation point. The routine use of transesophageal echocardiography in patients undergoing surgical myectomy for the treatment of obstructive hypertrophic cardiomyopathy is recommended. PMID- 1607538 TI - Hypertrophic cardiomyopathy and intraoperative echocardiography: too much of a good thing may be dangerous. PMID- 1607539 TI - Coexistence of mitral valve prolapse in a consecutive group of 528 patients with hypertrophic cardiomyopathy assessed with echocardiography. AB - Hypertrophic cardiomyopathy and mitral valve prolapse are both conditions that may be genetically transmitted and incur a risk for sudden cardiac death. Although the small left ventricular cavity and distorted geometry characteristic of hypertrophic cardiomyopathy might suggest a predisposition to mitral valve prolapse, the frequency with which these two entities coexist and the potential clinical significance of such an association are not known. To further define the relation of hypertrophic cardiomyopathy and mitral valve prolapse, 528 consecutive patients with hypertrophic cardiomyopathy were studied by echocardiography. Patients ranged in age from 1 to 86 years (mean 45); 335 (63%) were male. Unequivocal echocardiographic evidence of systolic mitral valve prolapse into the left atrium was identified in only 16 (3%) of the 528 patients. The mitral valve excised at operation from three of the patients had morphologic characteristics of a floppy mitral valve, which was judged to be responsible for the echocardiographic findings. Occurrence of clinically evident atrial fibrillation was common in patients with hypertrophic cardiomyopathy and mitral valve prolapse (9 [56%] of 16). Hence, in a large group of patients with hypertrophic cardiomyopathy, the association of echocardiographically documented mitral valve prolapse was uncommon. The coexistence of mitral valve prolapse in patients with hypertrophic cardiomyopathy appears to predispose such patients to atrial fibrillation. PMID- 1607540 TI - Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans. AB - A reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 +/- 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin. In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by greater than or equal to 10 ejection fraction units to less than 55%), the isovolumetric relaxation time was prolonged (from 66 +/- 18 to 84 +/- 24 ms, p less than 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction. A greater than 37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose. In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment. PMID- 1607541 TI - Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography. AB - Protruding atheromas of the aortic arch identified by transesophageal echocardiography have been implicated as a cause of stroke in elderly patients. One hundred thirty patients greater than or equal to 65 years of age were studied with intraoperative transesophageal echocardiography to detect aortic arch protruding atheromas and determine if these patients were at higher risk for perioperative stroke. Protruding atheromas were identified in 23 (18%) of 130 patients. In 19 (83%) of these 23 patients, palpation of the aortic arch at operation did not identify significant abnormalities. Five patients (4%) had perioperative stroke. Logistic regression identified aortic arch atheroma as the only historical or procedural variable that was predictive of stroke (odds ratio 5.8, 95% confidence interval 1.2 to 27.9, p less than 0.03). A history of peripheral or cerebrovascular disease, presence of aortic calcification, cardiac risk factors, age and duration of cardiopulmonary bypass did not predict stroke. In contrast, patients with protruding atheromas with mobile components were at highest risk. There were 3 (25%) of 12 patients with a mobile atheroma who had a stroke versus 2 (2%) of 118 patients without a mobile atheroma (chi-square = 10.3, p = 0.001). Displacement and detachment of the frail, protruding atherosclerotic material by aortic arch cannulation or by the high pressure jet emanating from the cannula tip may play an important role in the creation of embolization and stroke. PMID- 1607542 TI - Cutaneous and coronary flow reserve in patients with microvascular angina. AB - Microvascular angina is characterized by exercise-induced angina in patients with normal coronary arteries and reduced coronary flow reserve. Recently, a generalized disorder of abnormal vascular reactivity in microvascular angina has been postulated. Therefore, coronary flow reserve was determined by the coronary sinus thermodilution technique and compared with the cutaneous flux ratio in 6 control subjects (group 1) and 12 patients with microvascular angina (group 2). Coronary flow reserve was calculated from maximal coronary flow after 0.5 mg/kg of dipyridamole divided by flow at rest. Cutaneous flow ratio was estimated by laser Doppler fluxmetry (right forearm) before and after 4 min of suprasystolic blood pressure occlusion. Coronary flow at rest was identical in the two groups, but after maximal vasodilation with dipyridamole, coronary flow was higher in group 1 than in group 2 (p less than 0.05). Coronary flow reserve differed significantly between the two groups (2.9 in group 1 and 1.3 in group 2; p less than 0.001). Cutaneous Doppler flux at rest was higher in group 1 than in group 2 (p less than 0.05). However, the hyperemic response was identical in both groups. It is concluded that the cutaneous flux ratio in patients with microvascular angina is not impaired. Local peripheral vasomotor tone appears to be increased in patients with microvascular angina because cutaneous flow at rest is reduced. Thus, a generalized disorder of abnormal vascular reactivity cannot be confirmed in patients with microvascular angina. PMID- 1607543 TI - Viral myocarditis mimicking acute myocardial infarction. AB - Anecdotal reports have shown that myocarditis can mimic acute myocardial infarction with chest pain, electrocardiographic (ECG) abnormalities, serum creatine kinase elevation and hemodynamic instability. Thirty-four patients with clinical signs and symptoms consistent with acute myocardial infarction underwent right ventricular endomyocardial biopsy during a 6.5-year period after angiographic identification of normal coronary anatomy. Myocarditis was found on histologic study in 11 of these 34 patients. Cardiogenic shock requiring intraaortic balloon support developed within 6 h of admission in three (27%) of the patients with myocarditis. The mean age of the group with myocarditis was 42 +/- 5 years. A preceding viral illness had been present in six patients (54%). The ECG abnormalities were varied and included ST segment elevation (n = 6), T wave inversions (n = 3), ST segment depression (n = 2) and pathologic Q waves (n = 2). The ECG abnormalities were typically seen in the anterior precordial leads but were diffusely evident in three patients. Left ventricular function was normal in six patients and globally decreased in the remaining five patients, whose ejection fraction ranged from 14% to 45%. Lymphocytic myocarditis was diagnosed in 10 patients, and giant cell myocarditis was detected in the remaining patient. Four patients with impaired left ventricular function received immunosuppressive therapy with prednisone and either azathioprine (n = 2) or cyclosporine (n = 2). All six patients whose left ventricular function was normal on admission remain alive in functional class I. Of the five patients with impaired systolic function, ejection fraction normalized in three of the four patients who received immunosuppressive therapy within 3 months of treatment and in the one patient who received only supportive therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607544 TI - Hemodynamic effects of intranasal cocaine in humans. AB - Intranasal cocaine, 2 to 3 mg/kg body weight, is a commonly used local anesthetic for rhinolaryngologic procedures, and many persons who abuse it ingest a similar amount. Previous studies in humans showed that this dose of cocaine causes coronary vasoconstriction, and studies in animals showed that larger amounts given intravenously diminish myocardial performance. This study assessed the hemodynamic effects of intranasal cocaine, 2 mg/kg, in humans. In 15 patients (8 men and 7 women, aged 30 to 70 years) referred for cardiac catheterization, heart rate, systemic arterial pressure, cardiac index, pulmonary capillary wedge and pulmonary artery pressures and left ventricular pressure and its first derivative (dP/dt) were measured before and 15, 30 and 45 min after intranasal administration of saline solution (n = 5) or cocaine, 2 mg/kg (n = 10). No variable changed with saline solution. In those given cocaine, there was an increase in heart rate (17 +/- 16%, mean +/- SD), mean systemic arterial pressure (8 +/- 7%), cardiac index (18 +/- 18%) and positive and negative dP/dt (18 +/- 20% and 15 +/- 22%, respectively) (p less than 0.05 for all). Thus, intranasal cocaine in a dose similar to that used medicinally or "recreationally" does not exert a deleterious influence on intracardiac pressures and left ventricular performance. PMID- 1607545 TI - Transthoracic defibrillation: effect of sternotomy on chest impedance. AB - The purpose of this study was to determine the effect of sternotomy on transthoracic impedance, a major determinant of current flow and defibrillation success. Transthoracic impedance was determined by using a validated test-pulse technique that does not require actual shocks. Seventeen patients undergoing median sternotomy were studied prospectively. Transthoracic impedance was determined before operation, 3 to 5 days after operation and (in eight patients) greater than or equal to 1 month after operation. When measured using paddle electrodes placed in the standard apex-right parasternal defibrillating position, transthoracic impedance declined after sternotomy in all patients, from 77 +/- 18 to 59 +/- 17 omega (p less than 0.01); smaller declines were demonstrated by using other electrode positions. Transthoracic impedance remained below the preoperative level in the eight patients who underwent a second set of measurements at least 1 month after operation. Six normal subjects not undergoing sternotomy underwent serial transthoracic impedance measurements at least 5 days apart; mean transthoracic impedance did not change. It is concluded that transthoracic impedance declines after sternotomy. At any operator-selected energy level a higher current flow will result after sternotomy; this may facilitate postoperative defibrillation. PMID- 1607546 TI - Inflammatory cells and eicosanoid mediators in subjects with late asthmatic responses and increases in airway responsiveness. AB - To determine the relationship of inflammatory cells and eicosanoid mediators to the pathogenesis of the late asthmatic response (LAR) and increases in nonspecific airway responsiveness, we studied bronchoalveolar lavage (BAL) cells and fluid in 27 subjects 12 hours after inhaled antigen challenge. Methacholine challenge was performed before antigen challenge and 24 hours later (12 hours after BAL). Eight subjects had no LAR (-LAR, less than or equal to 10% fall in FEV1), nine subjects had an equivocal LAR (+/- LAR, 11% 25% fall in FEV1), and 10 subjects had a definite LAR (+LAR, greater than 25% fall in FEV1). Subjects developing +LAR had increased airway responsiveness at baseline compared with that of subjects developing an +/- LAR, but not with subjects having -LAR. If airway responsiveness was markedly increased at baseline, further increases after antigen challenge were often not observed. We found that both percent neutrophils and eosinophils increased in BAL as the severity of the LAR increased, but significant differences between the groups with -LAR and +LAR were only observed when both cell types were considered together. In addition, there was a significant correlation between the combined cell percentages and the severity of the LAR as determined by fall in FEV1. Likewise, increases in airway responsiveness were associated with significant increases in both neutrophil and eosinophil numbers, but only neutrophils correlated with the change in airway responsiveness after antigen challenge. However, despite the significant physiologic and cellular differences that we found between our groups, no significant differences could be found in BAL eicosanoid-mediator concentrations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607547 TI - Tryptase and histamine as markers to evaluate mast cell activation during the responses to nasal challenge with allergen, cold, dry air, and hyperosmolar solutions. AB - We have used assays for histamine and for the specific mast cell enzyme, tryptase, to examine the response of the nasal mucosa to provocation with several different stimuli and to evaluate the reliability of histamine as a marker of mast cell activation. High levels of histamine detected in baseline lavages of some subjects are not associated with any detectable tryptase, suggesting they are not mast cell derived. During pronounced immediate allergic responses, however, mast cell degranulation clearly occurs, and a striking correlation between histamine and tryptase is observed. This correlation is weaker when a more modest allergic response is induced, possibly reflecting differential diffusion of the two mediators across the epithelium. Provocation of susceptible individuals with cold, dry air leads to increased recoveries of both histamine and tryptase, confirming that mast cell degranulation occurs during this reaction. Although hyperosmolarity of the nasal mucosa may contribute to mast cell degranulation induced by cold, dry air, a brief exposure of the nasal cavity to hyperosmolar mannitol was not associated with measurable production of tryptase. The combined use of histamine and tryptase measurements can therefore provide useful evidence regarding the role of mast cell activation in the pathogenesis of inflammatory responses. PMID- 1607549 TI - Characterization and autoradiographic localization of histamine H1 receptors in human nasal turbinates. AB - To examine the localization of histamine H1 receptors (H1R) in human nasal mucosa, the autoradiographic distribution of H1R was studied in human nasal inferior turbinates. Cryostat sections were incubated with various concentration of [3H]pyrilamine in saturation-binding studies and with 1 nmol/L of [3H]pyrilamine for autoradiography. Nonspecific binding was determined by adding 2 mumol/L of pyrilamine. Scatchard analysis demonstrated high-affinity binding sites with a maximum binding capacity of H1R of 193 +/- 46 fmol/mg of protein, and dissociation constant was 0.6 +/- 0.1 nmol/L. Autoradiograms indicated H1R exist exclusively on the endothelium of vessels. No specific labeling could be observed in the submucosal glands or epithelium. These results extend and support our previous finding that histamine directly causes vascular permeability through H1R and stimulates nasal glandular secretion indirectly through reflexes. PMID- 1607548 TI - Aerosolized antigen exposure without adjuvant causes increased IgE production and increased airway responsiveness in the mouse. AB - Inhalation of an antigen, ovalbumin (OVA), in the absence of adjuvant has been demonstrated to induce an immune response that is associated with increased airway responsiveness. Determination of OVA-specific serum IgE and IgG antibody responses revealed an early increase in antibody titers that were initially restricted to the IgE class. Subsequently, IgG antibody titers increased and IgE antibody plateaued. Furthermore, we observed a tenfold increase in the number of lymphocytes caused by a predominant expansion of CD3+ T cells in the peribronchial-associated lymph modes (PBLNs) of sensitized animals compared with the numbers of cells in control animals or in the gut-associated lymphoid tissue. The sensitized animals demonstrated an increase in airway responsiveness to intravenous methacholine challenge. Analysis of in vitro immunoglobulin production by spleen mononuclear cells revealed increased spontaneous IgE production that was more than fourfold enhanced in the presence of OVA, but IgG production was not increased. Spleen and PBLN lymphocytes, but not lymphocytes from gut-draining lymph nodes, demonstrated a proliferative response to OVA. Control animals exhibited no proliferative response to OVA. Histopathologic examination of the sensitized lung revealed an absence of acute inflammatory cells (e.g., neutrophils and macrophages), lymphocytes, or monocytes at the time of the increased airway hyperresponsiveness. These data indicate that, after sensitization of mice by inhalation of antigen, the animals develop a specific IgE antibody response, expansion of PBLN lymphocyte numbers, and increased airway hyperresponsiveness in the absence of signs of airway inflammation. PMID- 1607550 TI - A comparative study of the effects of intranasal triamcinolone acetonide aerosol (ITAA) and prednisone on adrenocortical function. AB - A comparison of adrenocortical function before and after treatment with either intranasal triamcinolone acetonide aerosol (ITAA), prednisone, or placebo was done. Sixty-two male subjects with allergic rhinitis were treated for 6 weeks with either ITAA (220 or 440 micrograms/day), oral prednisone (10 mg/day), or placebo in double-blind, parallel-group fashion. Adrenocortical function was assessed by 6-hour cosyntropin stimulation before and at the end of the treatment period. The placebo-treated and two ITAA-treated groups produced no changes in adrenocortical function with treatment, and the ITAA-treated groups were not different from the placebo-treated group with mean +/- SEM changes in stimulated plasma cortisol (micrograms per deciliter) as follows: placebo, -2.68 +/- 1.77; ITAA 220 micrograms, -2.69 +/- 1.18; ITAA 440 micrograms, -2.96 +/- 1.81. The prednisone-treated group had a mean reduction in adrenocortical function (mean +/ SEM change in stimulated plasma cortisol of -19.8 +/- 1.77 micrograms/dl) that was significant (p less than 0.0001) compared with that of the placebo-treated group. The results of this study indicate that 6 weeks of treatment with 220 micrograms/day or 440 micrograms/day of ITAA has no effect on adrenocortical function, but prednisone, at a dosage of 10 mg/day for 6 weeks, produces partial adrenocortical suppression. PMID- 1607551 TI - Aspergillus fumigatus: identification of 16, 18, and 45 kd antigens recognized by human IgG and IgE antibodies and murine monoclonal antibodies. AB - The immunochemical properties of antigens produced by Aspergillus fumigatus were investigated with biochemical purification techniques in conjunction with the production of murine monoclonal antibodies (MAbs) and binding studies with human IgG and IgE antibodies. A. fumigatus antigens were partially purified by gel filtration and hydrophobic interaction chromatography on phenyl-Sepharose. Two fractions that eluted with either 2 mol/L or 0.15 mol/L of NaCl demonstrated strong binding to human IgG and IgE antibodies. Immunoprecipitation analysis with IgG antibodies from six patients with different Aspergillus-related diseases demonstrated that the 2M and 0.15M fractions contained major antigens of molecular weight 18 kd (Asp f I) and 45 kd, respectively. The 125I-labeled 2M fraction was used to compare IgG antibodies to A. fumigatus in sera from 25 patients with Aspergillus-related diseases. IgG antibodies were significantly higher in patients with allergic bronchopulmonary aspergillosis (geometric mean, 437 U/ml) than in patients with asthma (geometric mean, 14 U/ml; p less than 0.001), but undetectable (less than 5 U/ml) in 43/48 control subjects. A good correlation was found between levels of IgG antibodies to the 125I-labeled 0.15M fraction and the 125I-labeled 2M fraction in sera from 106 patients with cystic fibrosis (r = 0.77; p less than 0.001). Five murine IgG MAbs and two IgM MAbs were raised against the 2M fraction, and immunoprecipitation with the IgG MAb demonstrated two distinct antigens within the 2M fraction, Asp f I, and a 16 kd antigen. The results of a solid-phase RIA with IgG MAb 4A6 demonstrated that approximately 85% of A. fumigatus-allergic patients with allergic bonchopulmonary aspergillosis had IgE antibodies to Asp f I. The three protein antigens defined in these studies are useful probes for investigating the immunopathogenesis of diseases associated with colonization by A. fumigatus. PMID- 1607552 TI - Venom immunotherapy: 10 years of experience with administration of single venoms and 50 micrograms maintenance doses. AB - For the past 10 years, we have administered venom immunotherapy with single venoms, whenever it is possible, and maintenance doses of 50 micrograms. The choice of venoms was based on clinical history, skin test reactions, and a knowledge of venom cross-reactivity. There have been 258 re-stings in 108 patients with only three systemic reactions (2.7% per patient; 1.2% per sting). Two of these re-stings reactions were very mild, hives and facial edema, in patients who had had initial severe anaphylaxis. Five other patients had transient ill-defined symptoms, not considered allergic after re-stings. The patients covered a wide age range. Twenty-seven patients, nine under age 16 years, had initial dermal reactions only, and 44 patients had severe anaphylaxis. Most patients had multiple positive skin tests. Seventy-five patients received single venoms (yellow jacket, 58; honeybee, 15; hornet, 2), and 30 patients received two venoms. Re-stings occurred from 1 month to 8 years, (mean, 2 years) after starting treatment. Results indicate that this approach with 50 micrograms top doses and single venom immunotherapy may be sufficient in most patients with an associated decrease in the cost as well as possible increased morbidity associated with the use of multiple venom antigens. PMID- 1607553 TI - House dust mites and mite allergens in public places. PMID- 1607554 TI - Safety of venom immunotherapy administered by a cluster schedule. PMID- 1607555 TI - Sinusitis revisited. PMID- 1607556 TI - Testimony of the American Dietetic Association: non-insulin-dependent diabetes mellitus--an unrelenting but undeserved threat to the health of minorities. PMID- 1607557 TI - Dispensing with the renal diet for dialysis patients. PMID- 1607558 TI - Does a master's degree ensure better nutrition care? PMID- 1607559 TI - RDs know more than food. PMID- 1607560 TI - Iron supplementation study causes confusion. PMID- 1607561 TI - Roadblocks to identifying drug use in pregnant women. PMID- 1607562 TI - The Michigan approach: building consensus for safe weight loss. PMID- 1607563 TI - The food frequency method for dietary assessment. PMID- 1607564 TI - Comparison of two dietary questionnaires validated against multiple dietary records collected during a 1-year period. AB - The validity of two dietary history questionnaires was examined, one the Health Habits and History Questionnaire (HHHQ) developed by Block et al and the other a questionnaire developed by investigators at the University of Michigan (UM). The reference data consisted of the mean of four 4-day dietary records and recalls collected for 1 year before administration of the questionnaires. The sample of 85 persons included black and white men and women aged 25 to 50 years. The HHHQ was entirely self-administered; the UM questionnaire had both self- and interviewer-administered components. The HHHQ group means were similar to food record estimates for energy and most nutrients, whereas the UM questionnaire produced overestimates for energy and all nutrients examined. Correlations ranged from .31 to .60 (median = .48) for the UM questionnaire and from .42 to .68 (median = .57) for the HHHQ. Use of respondent-reported portion sizes with the HHHQ produced higher correlations than use of investigator-determined "standard" portion sizes (median r = .43 vs .57). Food frequency questionnaires can provide useful nutrient data for individuals as well as groups. PMID- 1607566 TI - Eating patterns and energy and nutrient intakes of US women. AB - A longitudinal multivariate analysis was used to determine whether differences in energy and nutrient intakes were present for women classified into different eating patterns. Ten multidimensional eating patterns were created based on the proportion of energy consumed at home and at seven away-from-home locations. Data were from 1,120 women aged 19 through 50 years who were surveyed up to six times over a 1-year period as part of the 1985 Continuing Survey of Food Intake by Individuals, US Department of Agriculture. Data from 5,993 days were analyzed. To examine differences in energy and nutrient intakes, longitudinal multivariate analyses were used to control for eating pattern and factors such as demographics, season, and day of week. Younger women in the Fast Food eating pattern consumed the greatest intakes of energy, total fat, saturated fat, cholesterol, and sodium. Well-educated, higher-income women in the Restaurant pattern consumed diets with the highest overall fat density. Nutrient densities for dietary fiber, calcium, vitamin C, and folacin were particularly low in away from-home eating patterns. In contrast, moderately educated, middle-aged and middle-income women in the Home Mixed eating pattern (70% at home, 30% away from home) consumed the most healthful diets. We conclude that knowledge of demographics such as income and education is not enough to target dietary interventions. Rather, educational efforts must consider both demographics and the location of away-from-home eating. This will allow development of behavioral change strategies that consider food choices dictated by the eating environment as well as personal knowledge and attitude factors related to adoption of healthful food choices. PMID- 1607565 TI - Validation of a self-reported shelf inventory to measure food purchase behavior. AB - A mailed, self-reported shelf inventory was validated for use as a tool in assessing the impact of a community nutrition intervention that included a point of-purchase component. The self-reported inventory was evaluated for overall accuracy as well as for the effects of gender, age, and shopping responsibility on accuracy. In addition, the food-shelf inventory was compared with a specific food frequency questionnaire. Specificity and sensitivity were calculated for self-reported inventories using an interviewer-completed, same-day inventory as the gold standard. Overall sensitivity was 86% and 87%, and overall specificity was 92% and 90% in two validation studies. Results show that the mailed, self reported shelf inventory is a valid measure of the presence or absence of particular foods in households. As such, it may be a useful tool for assessing the impact of point-of-purchase nutrition interventions. PMID- 1607567 TI - Nutrient intakes and body weights of persons consuming high and moderate levels of added sugars. AB - We classified a nationally representative sample of persons aged 4 years and older as high or moderate consumers of added sugars (ie, sugars added to foods by processors or consumers). Intake of added sugars was determined on the basis of grams consumed per kilogram of body weight (g/kg) and on the basis of percent of dietary energy from added sugars (% kcal). Regardless of the intake measure used, high consumers of added sugars had a significantly lower percentage of dietary energy from fat than did moderate consumers of added sugars. Persons defined by the % kcal measure as high consumers of added sugars took in lower percentages of the Recommended Dietary Allowances (RDAs) for 11 vitamins and minerals; these high consumers had body weights similar to those of their moderate counterparts. Persons defined as high consumers by the g/kg measure consumed greater percentages of the RDAs than did their moderate counterparts; these high consumers more frequently selected foods from categories likely to contain sugar rich foods but weighed significantly less than did moderate consumers. Thus, different approaches to defining intake of added sugars revealed two patterns of high consumption of added sugars with different levels of nutritional risk. Conditions of overweight were not associated with high intake of added sugars. Educational efforts, therefore, should focus on those consumers who tend to substitute foods rich in added sugars for more nutritionally desirable foods. PMID- 1607568 TI - Nutrient intake of urban and rural elderly receiving home-delivered meals. AB - We evaluated nutrient intake (as measured by a 3-day food record) and nondietary factors that may influence nutrient intake in urban (n = 48) and rural (n = 47) elderly clients in the Title III C home-delivered meal program. Mean nutrient intake did not differ significantly between the two populations; each population met or exceeded 100% of the Recommended Dietary Allowances (RDA) for all nutrients other than energy, vitamin B-6, calcium, magnesium, and zinc. However, 70% of the individuals within each population had intakes below 66% of the RDA for three or more nutrients and were thus classified as having poor diets. Factors such as the need for assistance with shopping and cooking, living situation, vitamin/mineral supplementation, prescription drugs, and dentition did not significantly predict nutritional intake in either the urban or the rural cohorts. However, 50% to 70% of both the rural and the urban homebound elderly needed assistance with cooking and shopping for food. The rural elderly relied on family members for help with shopping and cooking to a greater extent than did their urban counterparts. We conclude that nutrient intake of the homebound elderly is not affected by geographic location. However, both rural and urban clients are at risk for developing nutrient deficiencies. PMID- 1607569 TI - Irradiated or aseptically prepared frozen dairy desserts: acceptability to bone marrow transplant recipients. AB - Sterile ice cream and frozen yogurt were offered to immunosuppressed patients recovering from bone marrow transplantation. To obtain sterile products, two of the dairy desserts (prepackaged ice cream and frozen yogurt bars) were exposed to 40 kGy of cobalt 60 irradiation. Four different flavors of ice cream were aseptically prepared under a laminar airflow hood using commercially sterilized ingredients. A commercially sterile, frozen milk-based drink on the low-microbial menu served as the control. Ratings of the seven products by 17 patients indicated that a frozen vanilla milk-based drink and aseptically prepared chocolate ice cream were highly acceptable to recovery immunosuppressed patients who have difficulty eating most foods. However, the seven desserts received higher ratings from a sensory panel of healthy individuals than from the patient panel, confirming that new foods for the low-microbial diet should be "market tested" by the targeted patient population before inclusion in the menu. PMID- 1607570 TI - Nutrition knowledge of active-duty Navy personnel. AB - As evidence continues to mount implicating diet in the etiology of disease, the US Navy is developing nutrition education programs designed to reflect the consolidated dietary recommendations of national expert agencies. The purpose of this study was to provide a baseline assessment of the level of nutrition knowledge among Navy personnel. Forty true/false questions were developed to test nutrition knowledge as conveyed by the Navy's instructional manual for nutrition educators. The questionnaire was mailed to a representative sample of all active duty Navy personnel. Usable questionnaires were received from 2,938 participants (72.7% response rate). Mean number of correct items was 26.1 (65%). Nutrition knowledge was higher among older respondents, more highly educated personnel, whites, officers, women, and overweight individuals. Knowledge was weakest in the areas of calories/food intake and carbohydrates and strongest on vitamins/minerals and fiber. Program managers were recommended to intensify efforts to reach low-scoring subgroups, place more emphasis on the role of complex carbohydrates, disseminate guidelines for using nutrition labels on products, and develop point-of-choice nutrition education interventions for military dining facilities. PMID- 1607571 TI - Telephone surveys as a method for obtaining dietary information: a review. AB - The use of telephone surveys has increased significantly in the past decade. One advantage of telephone surveys is the ability to reach a large number of individuals: 97% of the US population owns telephones. Another advantage is cost savings: telephone surveys cost as little as one quarter to one half the amount of face-to-face surveys. Computer-assisted telephone interviewing has improved data collection, coding, and analysis. Random-digit dialing and a number of statistical advances such as weighting and stratification have significantly enhanced sample selection and research design of telephone surveys. The increasing need to collect dietary information from populations in an affordable fashion has expanded the use of telephone dietary surveys. To date, telephone dietary surveys have been used for follow-up after initial face-to-face contact has been made. The most common dietary instruments used are the 24-hour recall and the food frequency questionnaire. This review indicates that well-designed and well-administered telephone surveys are as good as, and may be better than, other methods for obtaining dietary information. PMID- 1607572 TI - Enteral nutrition in hyperemesis gravidarum: a new development. AB - Hyperemesis gravidarum occurs in up to 2% of pregnancies. Hospitalization is commonly required to treat dehydration and electrolyte and metabolic imbalances. Severe forms of hyperemesis gravidarum involving weight loss greater than 5% of prepregnancy weight have been associated with poor fetal growth and outcome. Hyperemesis gravidarum is a high-risk condition from a nutritional perspective. Traditional approaches to nutrition management focus on the cautious introduction of fluids and low-fat solids following resolution of acute nausea and vomiting. When trials of oral feeding fail to be tolerated, consideration should be given to the enteral route as the means of nutritional rehabilitation. A carefully designed delivery regimen combined with antiemetic therapy can prevent abdominal or sensory episodes that might precipitate further vomiting. Two case studies of the successful use of enteral nutrition in hyperemesis gravidarum are presented. Although clinical experience is limited and further research is needed, early results suggest that enteral nutrition in hyperemesis gravidarum is an effective and safe technique. PMID- 1607573 TI - Reimbursement enhancement in a New Jersey hospital: coding for malnutrition in prospective payment systems. PMID- 1607574 TI - Validation of two-dimensional models for estimation of portion size in nutrition research. PMID- 1607575 TI - Effect of prior notification on accuracy of dietary recall by the elderly. PMID- 1607576 TI - Comparison of 3-day food record and 24-hour recall by telephone for dietary evaluation in adolescents. PMID- 1607577 TI - Position of the American Dietetic Association: affordable and accessible health care services. AB - The American Dietetic Association supports the availability of a standard package of basic, comprehensive health services for all. The definition and evaluation of appropriate care and the linkage of care to patient outcomes are viewed as significant steps in enhancing the quality, efficiency, and effectiveness of the health care system. The Association is actively collaborating with others to enhance the ability of the health care system to direct limited health care resources to interventions of known effectiveness. PMID- 1607578 TI - White paper on health care reform. AB - It is the position of The American Dietetic Association that provision of nutrition services be included in any health care reform legislation. The dietetics professional (qualified dietitian) should be identified as a qualified provider of reimbursable nutrition services. PMID- 1607579 TI - Light to moderate alcohol consumption and mortality in the elderly. AB - OBJECTIVE: To determine whether there is a relationship of low to moderate alcohol consumption with cardiovascular mortality in the elderly. DESIGN: Prospective cohort studies with 5-year mortality follow-up. SETTING: Three populations of community-dwelling elders. PARTICIPANTS: Population-based cohorts of men and women, aged 65 or older, in three populations. Subjects with prior myocardial infarction, stroke, or cancer, as well as those lacking alcohol consumption data, were excluded from statistical analyses leaving 2,694 subjects in East Boston, Massachusetts, 2,293 subjects in Iowa, and 1,904 subjects in New Haven, Connecticut. MAIN OUTCOME MEASUREMENTS: Alcohol consumption, total mortality, cardiovascular mortality, and cancer mortality. RESULTS: Low to moderate alcohol consumption was associated with statistically significant lowered total as well as cardiovascular mortality in East Boston and New Haven. The relative risks of total mortality for low to moderate consumers of alcohol compared to those consuming no alcohol in the previous year were 0.7 (95% CI 0.6 0.8) in East Boston and 0.6 (95% CI 0.5-0.8) in New Haven. For cardiovascular mortality, the RRs were 0.6 in East Boston and 0.5 in New Haven (95% CI's exclude null). These results persisted after control for potential confounding variables. In Iowa, there were no significant differences in total or cardiovascular mortality according to alcohol consumption patterns. For cancer mortality, there were no significant associations with alcohol consumption in any of the three populations. CONCLUSIONS: These data suggest that the relationship of low to moderate alcohol consumption with reduced total and cardiovascular mortality, which are well documented in middle age, also occur in older populations. PMID- 1607580 TI - Alcohol as a risk factor for fall injury events among elderly persons living in the community. AB - OBJECTIVE: To determine if alcohol use is a risk factor for fall injury events among community-dwelling older persons. DESIGN: Case-control study. SETTING: South Miami Beach, Florida. PARTICIPANTS: 320 persons 65 or older who sought treatment at six area hospitals for injuries resulting from falls; 609 controls, matched for sex and age, selected randomly from Health Care Financing Administration (Medicare) files. MAIN INDEPENDENT VARIABLES: Self-reported current alcohol use. RESULTS: No association was found between fall injury events and average weekly alcohol use. CONCLUSIONS: Further efforts at reducing injuries to older persons from falls should concentrate on other modifiable risk factors, including adequate treatment of underlying medical conditions, reducing inappropriate psychotropic medication use, and installing safety devices in the home. PMID- 1607581 TI - Screening for drinking disorders in the elderly using the CAGE questionnaire. AB - OBJECTIVE: To assess the performance of the CAGE questionnaire in identifying elderly medicine outpatients with drinking problems. DESIGN: Cross-sectional design, with the alcohol module of the Diagnostic Interview Schedule as the criterion standard. SETTING: The outpatient medical practice of an urban university teaching hospital. PATIENTS: Consecutive patients 18 years or older who signed a consent form approved by the university's institutional review board. For this study, 323 patients greater than or equal to 60 years old. MAIN OUTCOME MEASURES: Sensitivity, specificity, receiver operating characteristics (ROC) curve and positive predictive value for CAGE scores of 0-4 for patients 60 years or older. RESULTS: Thirty-three percent of the sample group met study criteria for a history of drinking problems, including 63% of the male patients and 22% of the female patients. The sensitivity and specificity for a cut-off score of one for all patients was 86% and 78%, respectively, and 70% and 91% for a cut-off of two. The calculation of the area under the ROC curve was .86, and the positive predictive value of CAGE scores of 0-4 were 33%, 66%, 79%, 82%, and 94%, respectively. The predictive value for any score was higher in males than females, reflecting the higher prevalence of problems in the male population. CONCLUSIONS: The CAGE can effectively discriminate elderly patients with a history of drinking problems from those without such a history. The chosen cut off score should consider the prevalence of drinking problems in the population being tested. PMID- 1607582 TI - Effects of advancing age on the efficacy and side effects of antiarrhythmic drugs in post-myocardial infarction patients with ventricular arrhythmias. The CAST Investigators. AB - OBJECTIVE: To determine the effect of age on the response to anti-arrhythmic drugs. DESIGN: Randomized controlled trial comparing particular drugs. SETTING: Multi-institutional (The Cardiac Arrhythmia Suppression Trial, CAST). PARTICIPANTS: 2,371 patients, age less than 80, with ventricular arrhythmias after a recent myocardial infarction. Subjects classified by age as less than or equal to 55, 56-65, and 66-79 years. INTERVENTION: Upwardly titrated doses of encainide, flecainide or moricizine. After identification of a tolerated and effective dose of one of the drugs, participants were randomized to that drug and dose versus its placebo for up to 10 months. MAIN OUTCOME MEASURES: Efficacy of drug (suppression of ventricular premature depolarizations and/or non-sustained ventricular tachycardia), side effects and mortality. RESULTS: Older patients had more previous MIs, congestive heart failure (CHF), hypertension, NSVT, repolarization abnormalities, digitalis use, and diuretic use. They had less pathologic Q-waves or electrocardiographic injury pattern, and their left ventricular ejection fraction (LVEF) was lower. First dose VPD suppression with the first drug averaged 53% and is not associated with age (P = 0.29). Adverse events including death are more frequent in older patients taking study drugs (P less than 0.001). This trend is consistent in all three study drugs and at varying LVEFs. History of prior MI, low LVEF, VPD (in log scale), and digitalis therapy also correlates with adverse events (all P less than 0.05). Following adjustment for these factors, older age is an independent predictor of adverse events (relative risk 1.30 per decade of age, P less than 0.001). CONCLUSIONS: Older age increases the susceptibility to adverse cardiac events from a class of relatively toxic antiarrhythmic agents. PMID- 1607583 TI - Predictors of advance directive restrictiveness and compliance with institutional policy in a long-term-care facility. AB - OBJECTIVE: To ascertain factors influencing the level of advance directives selected by nursing home residents or surrogates and the time delay to documentation of these choices in the medical record after implementation of a facility-wide policy. DESIGN: Longitudinal cohort study of nursing home residents followed from date of advance directive policy initiation or time of admission for a maximum of 21 months from study commencement. SETTING: A 315-bed multilevel nursing home. PARTICIPANTS: Four hundred twenty-four nursing home residents (mean age 85, 74.9% female, 96.1% white). OUTCOME MEASURES: Level of advance directive status chosen--full code, do not resuscitate (DNR) or palliative care only--and date documented in the medical record. RESULTS: Factors predictive of restricted advance directives (DNR or palliative care) included age greater than 85 years (P = 0.025), documented use of a surrogate decision maker (P = 0.001), low physical function (P less than 0.001), low cognitive function (P less than 0.001), and having a nursing home-employed physician (P = 0.001). These results were confirmed using logistic regression models. Median time to directive documentation decreased from 54 days for residents admitted in the first quarter to 1 day for residents admitted in the fourth quarter of the year following initiation of an advance directive policy. CONCLUSION: In logistic models, nursing home-employed physicians were more likely to write restricted advance directive orders than community-based physicians even after controlling for resident age, cognitive status, and physical function. In addition, implementation of a formal nursing home advance directive policy can shorten time to physician documentation of resident advance directive status. PMID- 1607584 TI - Quantitative assessment of bed rise difficulty in young and elderly women. AB - OBJECTIVE: To describe the motions which occur during rising from bed, specifically the motions that appeared to characterize difficulty in rising from a bed in older adults. DESIGN: Development of a Mobility assessment tool. SETTING: Retirement center and two university laboratories. PARTICIPANTS: Three groups of female volunteers: young controls (n = 17, mean age 24), community dwelling older adults (n = 12, mean age 71), and retirement center-dwelling older adults who admitted to difficulty in rising from a bed (n = 15, mean age 86). INTERVENTION: Videotaping of motions occurring during controlled rises from a supine to sitting position. MAIN OUTCOME MEASURES: These motions were rated on the specially developed Bed Rise Difficulty (BRD) scale, a scale designed to measure movements that characterize difficulty in rising from a bed in older adults. Subject groups were compared in total BRD score, individual BRD item score, and total time to rise. Item relationships and scale reliability were also assessed. RESULTS: Older adults with no apparent difficulty in rising based on total time to rise or on the BRD score nevertheless showed differences in upper extremity use when compared to young controls. Older adult subjects with difficulty in rising from a bed, when compared to other older adults with no apparent difficulty, differed more often in their upper extremity and leg use to facilitate the rise. Five BRD scale items, including use of extremity pushes, discontinuity of trunk and leg motion, multiple shoulder/pelvic adjustments, multiple leg adjustments, and poor vertical heel clearance may have best indicated true bed rise difficulty. CONCLUSIONS: These data provide a reliable and valid method to characterize difficulty in rising from a bed and provide the basis for biomechanical analyses of the strength and joint ranges of motion required to rise from a bed. PMID- 1607585 TI - The diagnosis of small bowel bacterial overgrowth in elderly patients. AB - OBJECTIVE: To examine the frequency of small bowel bacterial overgrowth in elderly subjects. DESIGN: Prospective observational study. SETTING: Department of Health Care of the Elderly in a university teaching hospital. PATIENTS: Thirteen elderly control subjects having undergone normal gastroscopy with normal hematology and anthropometry; 39 consecutive referrals of elderly patients with clinical or biochemical evidence of malnutrition. MAIN OUTCOME MEASURES: Duodenal bacterial counts and the 14C-glycocholate, hydrogen, and 14C-xylose breath tests. RESULTS: Five of the 13 control subjects and 21 of 39 patients with malnutrition had high duodenal bacterial counts (greater than 10(5) organisms/mL), whereas only seven patients were judged to have clinically significant bacterial overgrowth. The 14C-xylose breath test showed a high specificity (89%) but a low sensitivity (30%) when compared with the results of duodenal culture. The hydrogen breath tests and the 14C-glycocholate test showed a similar picture of moderately high specificity and low sensitivity (77% and 20%, respectively, for the hydrogen breath test, 76% and 33%, respectively, for the 14C-glycocholate test). CONCLUSIONS: A positive xylose breath test was the best predictor of high duodenal bacterial counts. However, since many elderly subjects have high duodenal bacterial counts, the overdiagnosis of bacterial overgrowth syndrome will result if duodenal culture is relied upon exclusively. PMID- 1607586 TI - Validation of a telephone version of the mini-mental state examination. AB - OBJECTIVE: To assess the construct validity of a telephone-administered version of the Mini-Mental State Examination (MMSE). DESIGN: Validity testing by comparing a telephone version of the MMSE administered first to a face-to-face evaluation done several days later. SETTING: Outpatient geriatric assessment center. SUBJECTS: 100 of 175 consecutive referrals. MAIN OUTCOME MEASURES: MMSE and a brief neuropsychological screening test (BNPS) face-to-face and a telephone version of the MMSE as part of the Adult Lifestyles and Function Interview (ALFI MMSE). RESULTS: Test scores of the two MMSE versions correlated strongly for all subjects (Pearson's r = 0.85, P = 0.001) and remained significant for the cognitively intact (P = 0.02) and questionably (P = 0.002), mildly (P = 0.0001), and moderately (P = 0.003) demented. Comparison of the two versions' equivalent 22 items revealed no significant difference for scores of all subjects (P = 0.07) but with a trend toward higher scores in the original version. Diminished hearing, reported either by the subject (P = 0.003) or by the collateral source (P = 0.02) was associated with lower scores on the telephone version. Five individual test items were biased by the route of test administration. Sensitivity and specificity relative to the BNPS were 67% and 100% for the ALFI MMSE and 68% and 100% for the MMSE, respectively. CONCLUSION: The scores on the ALFI-MMSE correlated strongly with the scores of the original version given face to-face in subjects undergoing geriatric assessment. The results indicate that the ALFI-MMSE could be a useful and economical tool to screen for cognitive impairment. PMID- 1607587 TI - The efficacy and safety of maintenance ECT in geriatric patients. PMID- 1607588 TI - Pott's paraplegia: a complication of tuberculous spondylitis. PMID- 1607589 TI - Dizziness in older people. AB - Patients use the term dizziness to describe a sensation of altered orientation in space. Because visual, proprioceptive, somatosensory and vestibular signals provide the main information about the position of the head and body in space, damage to any of these systems can lead to a complaint of dizziness. Changes in the brain centers that integrate these orienting signals can also result in a sensation of dizziness. This review focuses on the pathophysiology, diagnosis, and management of the common causes of dizziness in older people. PMID- 1607590 TI - State statutes limiting advance directives: death warrants or life sentences? PMID- 1607591 TI - Prevention of mental disorder in the elderly: current perspectives and future prospects. AB - This article reviews primary, secondary, and tertiary preventive strategies in the mental health field. Primary prevention is currently restricted to some forms of dementia, but secondary and tertiary prevention can significantly diminish both short-term and long-term morbidity. Improved professional and lay education, better use of existing knowledge and resources, and improved communication among practitioners in the medical, psychosocial, and mental health fields can all lead to improved care at the present time. PMID- 1607592 TI - Serum total cholesterol in atherothrombotic brain infarction. PMID- 1607593 TI - An outbreak of pediculosis in a retirement hotel. PMID- 1607594 TI - Three-wheeled walkers. PMID- 1607595 TI - Vitamin deficiency in the nursing home. PMID- 1607596 TI - Quantitative effects of sympathetic and vagal nerve stimulations on sinus and AV junctional rhythms. AB - Responses of the sinus node and atrioventricular (AV) junctional pacemakers to autonomic denervation and to individual stimulations of the right and left stellate and both vagi were studied in 33 anesthetized dogs. Autonomic denervation depressed sinus node automaticity by only 18% from control, whilst AV junctional automaticity was reduced by 48.5% from control. Sympathetic and parasympathetic stimulation frequency-response curves (0.25, 0.5, 1, 2, 4, 8, 16 and 32 Hz) were obtained. In the sinus node the chronotropic responses to sympathetic stimulations reflect a bilaterally asymmetrical innervation with a right sided preponderance. In contrast, sinus slowing in response to either right or left vagal stimulations were indistinguishable when lower frequencies of stimulation were used. At 4 Hz and higher frequencies there is a right vagal preponderance. The AV junctional chronotropic responses suggest that this major subsidiary pacemaker receives a bilaterally symmetrical autonomic innervation. The chronotropic responses to individual nerve stimulations expressed as percent changes in sinus rate and AV junctional rate from their respective controls after autonomic denervation show that the AV junction is far more responsive than the sinus node to both sympathetic and parasympathetic stimulations. To allow for more meaningful comparisons the data were normalized using the respective maximum increase and maximum decrease of sinus node and AV junctional rates to left and right sympathetic and parasympathetic stimulations as the 100% reference. These normalized curves show that 50% of the maximal chronotropic responses were always achieved at a lower stimulus frequency in the AV junction than in the sinus node; shift of the AV junctional response curves to the left of the sinus node response curves by a 0.2 (sympathetic) and 0.3 (parasympathetic) log units was observed. These studies further showed that sympathetic activity in the AV junction is an absolute prerequisite to maintain regular AV junctional rhythms especially during the bradycardic episodes evoked in the study of vagal stimulus frequency-response curves. PMID- 1607597 TI - Immunohistochemical study of synaptophysin distribution in the superior cervical ganglion of newborn and adult rats. AB - Intense synaptophysin immunoreactivity was observed around neuronal cell bodies and in the neuropil of the superior cervical ganglion of adult rats. In newborn rats synaptophysin was comparatively less concentrated and restricted to small interstitial spaces. In contrast, in newborns, consistent traces of positivity were found in the Golgi-like area of larger neurons, in agreement with the higher neonatal rate of synaptophysin synthesis. A few clusters of small neurons, numerically more expanded in adult rats, exhibited a dense reaction product filling the whole cytoplasm. No positivity was found in intraganglionic fibres. PMID- 1607598 TI - The influence of the vagally induced rebound contractions on the non-adrenergic, non-cholinergic (NANC) inhibitory motility of the rabbit stomach and the role of prostaglandins. AB - Factors influencing the vagally induced rebound contraction and its role in gastric inhibitory motility were studied in the anaesthetised rabbit. Gastric motility was assessed from measurements of gastric volume by means of an intragastric balloon. In the atropine- and guanethidine-treated animals, vagal stimulation caused biphasic motor responses: a rapid relaxation was followed by a rebound contraction. The latter, depending on experimental conditions, was able to restore and maintain gastric volume at the basal level. However, the rebound contraction was greatly influenced by the stimulation parameters and the basal gastric volume. Stimulation periods of less than 30 sec, or stimulation frequencies above 20 Hz, as well as basal gastric volumes above 70 ml could reduce the amplitude of the post-stimulus excitatory motility, and transformed the biphasic response into a triphasic one: a slow, long-lasting relaxation appeared after the rebound contraction. Prostaglandin-synthesis inhibitors of the non-steroidal anti-inflammatory group depressed the rebound contraction, and caused persistence of gastric relaxation, even after the offset of vagal stimulation. PGE2 evoked excitatory motor responses which closely mimicked the vagally induced rebound contraction. PGE2 also interrupted the rapid or slow, long-lasting relaxant responses. PGF2 alpha elicited tonic excitatory responses. These results suggest that PGE2 is involved in the mechanism underlying post stimulus excitatory motility. They also suggest that the rebound contraction is a key factor in determining the inhibitory motility pattern of the rabbit stomach. PMID- 1607599 TI - Nerve growth factor effects on inhibition by submandibular gland ablation or autonomic denervation of activity-induced parotid growth. AB - Present data confirm our earlier report that an increase in [3H]thymidine incorporation into DNA of parotid gland occurs with reintroduction of solid chow to rats previously maintained on liquid diet; if, however, the submandibular sublingual glands are removed prior to the dietary substitution, the increase is prevented (present data and [19]). In addition, present data show that administration of nerve growth factor (NGF) to partially sialoadenectomized rats during the 2-day period of dietary change from liquid to solid diet restores thymidine values to the high levels observed following the dietary change in intact animals. However, the increase in gland size that accompanied the change in dietary consistency was not prevented by prior submandibular gland ablation, and administration of NGF had no influence on gland size or cell size. The removal of both the sympathetic and parasympathetic nerves to the parotid gland prior to the dietary manipulation also suppressed [3H]thymidine incorporation into parotid, and values did not differ from chow controls. The data show that NGF, a submandibular growth factor, has a prominent role in regulation of the autonomically-mediated hyperplastic response. However, neither the submandibular gland nor NGF has an important role in regulation of the increase in gland size that also accompanies the dietary change. PMID- 1607600 TI - A commentary on the morphological identification of interstitial cells of Cajal in the gut. PMID- 1607601 TI - Evidence for inhibitory nicotinic and facilitatory muscarinic receptors in cholinergic nerve terminals of the rat urinary bladder. AB - Cholinergic prejunctional modulatory receptors on parasympathetic nerves in the rat urinary bladder were studied by measuring 3H-acetylcholine (ACh) release in muscle strips from the bladder body. Electrical field stimulation markedly increased 3H-ACh overflow in strips preloaded with 3H-choline. Oxotremorine (1 microM), an M2 receptor agonist and DMPP (10 microM) a nicotinic (N) receptor agonist decreased the release of ACh (50% and 55% respectively); whereas McN-A 343 (50 microM) an M1 receptor agonist increased the release (33%), indicating the presence of three types of modulatory receptors. The anticholinesterase agent, physostigmine in concentrations of 1, 5 and 25 microM and neostigmine (5 microM) increased ACh release (44-710%). However a low concentration of physostigmine (0.05 microM) decreased release. Pirenzepine, an M1 muscarinic antagonist or atropine blocked the increased ACh release in physostigmine-treated strips, but in normal strips pirenzepine did not change release and atropine increased release. McN-A 343 or prolonged application (15 min) of DMPP increased ACh release (376% and 391% respectively) in physostigmine-treated strips. The response to McN-A 343 was blocked by pirenzepine. d-Tubocurarine (DTC), a nicotinic receptor blocker, enhanced ACh release in the presence of physostigmine but proved to be ineffective in normal preparations. These findings suggest that all three cholinergic receptors (M1 facilitatory, N inhibitory and M2 inhibitory) are activated by endogenous ACh in physostigmine treated preparations whereas only M2-inhibitory receptors are activated in normal preparations. It will be important in future studies to determine whether M1 and M2 mechanisms can also be activated under more physiological conditions in the bladder and whether they are present at other cholinergic synapses. PMID- 1607602 TI - Selective excitation of parasympathetic nerve fibers to elicit the vasodilatation in cat lip. AB - Electrical stimulation of the tongue and the proximal cut end of the lingual nerve caused a blood flow to increase in a stimulus-intensity dependent manner in the ipsilateral lower lip of the cats. Pretreatment with hexamethonium (an autonomic ganglionic blocker, 1.0 mg/kg) abolished the vasodilator response, while atropine, phentolamine, propranolol and tripelennamine had no effect on these vasoresponses. Ipsilateral sections of either the glossopharyngeal nerve root, inferior alveolar nerve or mental nerve at the main mental foramen, but not at the posterior mental foramen, abolished the vasodilator response caused by electrical stimulation of the tongue and the lingual nerve. Electrical stimulation of the distal cut ends of the glossopharyngeal nerve root and inferior alveolar nerve caused the vasodilator and vasoconstrictor responses, whereas stimulation of the tongue and the proximal cut ends of the lingual nerve did not elicit the vasoconstrictor response. These results suggest that reflex vasodilatation in the cat mandibular division is exclusively mediated via activation of the parasympathetic nerve fibers, and that selective excitation of the parasympathetic nerve fibers in the oral area is possible. PMID- 1607603 TI - Isolated hypertensive lower esophageal sphincter. Clinical and manometric aspects of an uncommon esophageal motor abnormality. AB - The hypertensive lower esophageal sphincter is an infrequent primary esophageal motor disorder characterized by elevated mean lower esophageal sphincter pressure (greater than or equal to 3 SD from that of controls), sphincter relaxations greater than 75%, and normal peristaltic activity in the esophageal body. This disorder is frequently associated with the nutcracker esophagus. We report our clinical and manometric experience with the isolated hypertensive lower esophageal sphincter (i.e., unassociated with other motor disorders), which constituted 2.7% of all patients who complained of dysphagia or chest pain referred for manometry during the period from October 1982 to February 1991. PMID- 1607604 TI - Serum iron, ferritin, and vitamin B12 during prolonged omeprazole therapy. AB - Since gastric acid plays an important role in the absorption process of iron and vitamin B12, we determined levels of iron, ferritin, vitamin B12, and folic acid in 75 serum samples obtained during continuous omeprazole therapy (6-48 months after start of therapy) from 34 patients with peptic diseases (primarily reflux esophagitis). Serum iron and ferritin levels were decreased in two and three patients, respectively, but there is little evidence that omeprazole administration was causally related to these findings. Serum vitamin B12 and folic acid levels were normal in all cases. We conclude that iron, vitamin B12, and folic acid malabsorption is unlikely to occur, at least within the initial 3 4 years of continuous omeprazole therapy. PMID- 1607605 TI - Correlation between IgA antiendomysial antibodies and subtotal villous atrophy in dermatitis herpetiformis. AB - Serum IgA antiendomysial antibodies (EmA) were present in 20 (64.5%) of 31 patients with dermatitis herpetiformis (DH) on a normal diet. A significant correlation was found between these antibodies and the severity of gluten-induced jejunum damage. IgA EmA were positive in 19 (86%) of the 22 DH patients with subtotal villous atrophy, in comparison with the positivity of only one (11%) of the nine DH patients with less severe intestinal involvement (partial villous atrophy or mild abnormalities). The specificity of this test for gluten-sensitive enteropathy was 100%, these antibodies being consistently negative in biopsied disease controls showing a normal jejunal mucosa. Moreover, IgA EmA proved to be useful in monitoring the response to gluten withdrawal in DH patients, as these antibodies always disappeared in all the DH cases studied after 1 year of gluten free diet together with the regrowth of jejunal villi. The strict relationship between IgA EmA and subtotal villous atrophy is more helpful still since the enteropathy present in DH is usually symptomless and therefore difficult to suspect. PMID- 1607606 TI - Microbic superinfection in relapse of inflammatory bowel disease. AB - To assess the association between symptomatic relapse of inflammatory bowel disease (IBD) and superinfection with enteropathogenic microorganisms, we determined prospectively the incidence of infections with enteropathogenic bacteria, protozoa, and helminths in patients with confirmed longstanding IBD. Sixty-four patients with IBD (49 with Crohn's disease [CD] and 15 with ulcerative colitis [UC]) were consecutively enrolled in the study when relapse occurred. Multiple biopsies for histological and microbiological investigations were taken from all patients who were evaluated by colonoscopy. Parallel stool specimens were investigated for the presence of enteropathogenic bacteria, protozoa, and helminths. In six patients, we detected Clostridium difficile or toxin B (five CD, one UC), in one patient Campylobacter jejuni (CD), and in another patient Salmonella typhimurium (UC). Enteropathogenic Escherichia coli were isolated from three patients. Investigation of biopsies for Mycobacteria, microscopic examination of stool samples for helminths, and immunofluorescence for chlamydia were negative in all patients. In summary, as we found enteropathogenic microorganisms so infrequently in patients with relapse of IBD, despite intensive microbiological screening by tissue sampling for detection of gut adherent bacteria, we believe that microorganisms play only a minor role in the exacerbation of IBD. PMID- 1607607 TI - Inflammatory bowel disease: costs-of-illness. AB - We have evaluated the economic costs to society for the two major types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, using a medical decision algorithm costing methodology augmented by examination of 1988 89 claims data from a major U.S. commercial insurer. The average annual medical cost per patient with Crohn's disease was estimated at $6,561 (1990 U.S. dollars). The total annual medical costs for U.S. Crohn's disease patients in 1990 was estimated at $1.0-1.2 billion. The average annual medical cost per patient with ulcerative colitis was estimated at $1,488. The total annual medical costs for U.S. patients with ulcerative colitis in 1990 was estimated at $0.4-0.6 billion. Adjusting for productivity losses, we estimated the annual economic cost for both diseases at $1.8 billion to $2.6 billion. Analysis of insurance claims data for inflammatory bowel disease patients showed that the distribution of annual medical expenses charged and paid is highly uneven by patient. The top 2% of Crohn's disease patients accounted for 28.9% of total charges and 34.3% of the total amount paid. The top 2% of ulcerative colitis patients accounted for 36.2% of total charges and 39.0% of the total amount paid. We used a multivariate regression model to examine potential cost-effectiveness tradeoffs between different types of medical services in treatment of inflammatory bowel disease. PMID- 1607608 TI - Inflammatory bowel disease: medical cost algorithms. AB - In this study we describe medical cost estimates for the two major types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, using a literature-based medical decision algorithm costing methodology. Surgery and inpatient costs were estimated to account for roughly half of inflammatory bowel disease medical costs. Outpatient medical care represented only 3.0-7.1% of average cost of medical care for inflammatory bowel disease; initial diagnostic workups were only 1.5-7.8% of medical costs. Long-term complications were estimated to average $439 for ulcerative colitis, nearly twice the average for Crohn's disease. Medications averaged about 10% of total costs. The average annual medical cost per patient with Crohn's disease was estimated at $6,561 (1990 U.S. dollars). The total annual medical costs for U.S. Crohn's disease patients in 1990 was estimated at $1.0-1.2 billion. The average annual medical cost per patient with ulcerative colitis was estimated at $1,488. The total annual medical costs for U.S. patients with ulcerative colitis in 1990 was estimated at $0.4-0.6 billion. PMID- 1607609 TI - Can NSAIDs cause acute biliary pain with cholestasis? AB - Two patients had many acute episodes of biliary pain with elevated liver function tests 12-48 h after the last ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) (including paracetamol) alone or in combination with codeine. One had known intolerance to NSAIDs, but paracetamol had not been previously incriminated in the pathogenesis of the attacks. In this patient the combined use of paracetamol and codeine probably also increased the severity of the episodes. We conclude that in some patients in whom endoscopic cholangiography is normal, biliary pain and abnormal liver function tests could be the result of NSAIDs. A thorough drug history is required in such cases. PMID- 1607610 TI - Right colon adenocarcinoma presenting as Bacteroides fragilis liver abscesses. AB - Pyogenic abscesses of the liver occur in association with a variety of diseases. Sometimes they are caused by anaerobic infections of liver metastases. Uncommonly, however, multiple hepatic abscesses caused by anaerobic bacteria are the presenting signs of unsuspected colonic cancer in the absence of liver metastases. We report a 60-year-old man who presented with febrile cholestatic liver disease initially thought to be metastases. Repeated ultrasound-directed liver biopsies yielded a diagnosis of multiple abscesses. Bacteroides fragilis was grown from the liver specimen and the patient responded well to metronidazole treatment. Two months later, however, overt symptoms of large bowel disease led to the diagnosis of colonic adenocarcinoma. After a 6-month postoperative follow up, the patient is free of liver metastases. Anaerobic liver abscesses should always alert the clinician to possible silent colonic cancer. PMID- 1607611 TI - Rectal prolapse after oral cathartics. AB - Complete rectal prolapse or procidentia is an uncommon condition long recognized but of uncertain pathogenesis. We report two patients, seen a decade apart, both of whom developed complete rectal prolapse after ingestion of oral cathartics in preparation for diagnostic studies. To our knowledge, cathartic-induced complete rectal prolapse has not been reported previously in the current medical literature, despite the thousands of bowel preparations performed annually. These two cases address the implications of such an occurrence, and we discuss the pertinent management issues. PMID- 1607612 TI - Etiology and course of acute bleeding esophageal ulcers. AB - Twenty (2%) of 1,140 patients with acute gastrointestinal bleeding had esophageal ulcers. Patients with esophageal ulcers most commonly had either melena (40%) or melena and hematemesis (40%). Fifty percent had orthostatic hypotension, and 80% required transfusions. Ulcers were associated with nonsteroidal anti-inflammatory drugs (NSAIDs) use in 50%, hiatal hernia in 60%, and esophagitis in 40%. Endoscopic stigmata of recent hemorrhage consisted of oozing blood (35%) and adherent clot (25%). Six patients had multiple ulcers. The majority of ulcers (90%) were in the distal esophagus. Nine patients were endoscopically treated without complications except for rebleeding in 1 patient. Endoscopic therapy was associated with decreased duration of hospitalization. Overall mortality was 45% in these patients, but no deaths were related to bleeding. Although uncommon, esophageal ulcers are a cause of significant acute gastrointestinal bleeding that appears to respond to endoscopic treatment. PMID- 1607613 TI - Familial aggregation of Crohn's disease and ankylosing spondylitis in a mother and her son. PMID- 1607614 TI - Unusual presentation of a hemorrhagic pancreatic pseudocyst. PMID- 1607615 TI - Segmental macroscopic colitis associated with collagenous colitis. PMID- 1607616 TI - Lipoma of the omentum presenting as acute cholecystitis. PMID- 1607617 TI - Is it useful to follow-up intestinal metaplasia in the stomach? Analysis of cost/effectiveness. PMID- 1607618 TI - Accuracy of blood ethanol determination using serum osmolality. AB - A retrospective review of 81 emergency department patients was performed to determine the accuracy of blood ethanol levels (BEL) calculated from serum osmolality. The osmolar gap (measured-calculated serum osmolality) was used to determine the calculated BEL. The mean difference between calculated and measured BEL was 49.2 mg/dL. Calculated BEL overestimated measured BEL in 83% of patients. Adding a correction factor for unmeasured osmoles to the equation for calculated serum osmolality will reduce this error. PMID- 1607619 TI - Lawn mower injuries: a case report. AB - Frequent and varied injuries are sustained during the operation of power lawn mowers in the United States. A description of one such injury leading to cardiac trauma is presented. The clinical signs of injury were initially unclear, and obtaining accurate historical data was vital in the diagnosis of this patient. PMID- 1607621 TI - Umbilical inflammatory conditions: case report and differential diagnosis. AB - Umbilical inflammatory conditions may result from a variety of congenital and acquired abnormalities, some of which may be life threatening. An understanding of the developmental anatomy of the umbilicus provides a basis for formulating an approach to both evaluation and treatment of these conditions. A case report is presented. PMID- 1607620 TI - Acute abdominal aortic occlusion. AB - Acute occlusion of the infrarenal abdominal aorta is a catastrophic event requiring early recognition and intervention if permanent disability is to be decreased or avoided. While traditional causes of occlusion (saddle embolus and thrombosis) are the most frequent, vasculitis and hypercoagulable states have recently been suggested as etiologies. This article presents three cases of acute abdominal aortic occlusion from different mechanisms and reviews the literature concerning presentation and management. PMID- 1607622 TI - Peripartum cardiomyopathy: a case report. AB - Peripartum cardiomyopathy (PPCM) is a relatively rare form of acute heart failure. Onset is from the last trimester of pregnancy to 5 months postpartum. Diagnosis is made by excluding other causes of acute heart failure, such as infections or toxins, and by determining that the patient does not have an underlying cardiac problem that has been unmasked by pregnancy. Diagnosis in the last trimester is complicated by the fact that the early symptoms of this disorder may mimic the symptoms of normal pregnancy. PPCM must be considered in any patient who presents with new onset peripheral edema, dyspnea on exertion, or paroxysmal nocturnal dyspnea during late pregnancy or up to 5 months postpartum. Limited studies suggest that early and aggressive therapy is associated with a better outcome. Therapy is directed toward decreasing preload and improving cardiac function. Return of cardiac size to normal is associated with a better prognosis than continued cardiomegaly. PMID- 1607623 TI - Hydrofluoric acid: a review of toxicity. AB - Hydrofluoric acid is a toxic substance used widely in both industrial and domestic settings. It can cause severe burns, as well as systemic toxicity. Death has been reported from as little as 2.5% body surface area (BSA) burn involving concentrated acid. Topical and parenteral calcium salts have proven effective therapy for both dermal and systemic manifestations. All emergency physicians should be aware of the unique complications and treatment of these injuries. PMID- 1607624 TI - Cocaine-induced myocardial infarction: an analysis and review of the literature. AB - The objectives of this paper are to analyze the case reports of cocaine-induced myocardial infarction and to better define the clinical characteristics of this syndrome. An English language literature search was carried out using MEDLINE, and a bibliographic review of all identified articles and book chapters was conducted. Ninety-one cases of cocaine-induced myocardial infarction were identified. Intranasal, intravenous, and inhalational routes of abuse all resulted in myocardial infarction. Fourty-four percent of patients had previously noted chest pain. Eighty-seven percent of patients were cigarette smokers. Two thirds of patients had their myocardial infarction within 3 hours of the use of cocaine (with a range of 1 minute to 4 days). Cardiac catheterizations were abnormal in 30 of 54 patients (55%). Of the 24 patients with reported follow-up, 14 (58%) had further ischemic events after discharge. In conclusion, cocaine induced myocardial infarction identifies a group of young individuals who may be prone to recurrent complications after initial presentation. PMID- 1607625 TI - The modified clove hitch: a technique to maintain endotracheal tube position in the intubated patient. AB - We describe the technique of using a modified clove hitch made of nasal cannula tubing as a means of insuring the position and security of an endotracheal tube in the intubated patient. Our experience indicates that this tie works well in both the prehospital and emergency department settings. We suggest that the modified clove hitch is a valuable adjunct to emergency airway management. PMID- 1607626 TI - Nontraumatic spinal cord compression. AB - Nontraumatic spinal cord compression can have very dramatic clinical presentations with rapid onset of symptoms and quickly ensuing paralysis. The manifestations may be much more subtle. This text will discuss the four most common causes of myelopathy, including spinal canal hemorrhage, spinal abscess, compression by tumor, and skeletal disease. Compressive lesions to the spinal cord from other than these etiologies are rare. PMID- 1607627 TI - The great mutilator of American youth. PMID- 1607628 TI - Variations in acromial ossification simulating infant abuse in victims of sudden infant death syndrome. PMID- 1607629 TI - Endotracheal intubation following diazepam or lorazepam in status epilepticus. PMID- 1607630 TI - Call pay. PMID- 1607631 TI - Objectives to direct the training of emergency medicine residents on off-service rotations: administration. AB - Administrative knowledge and skills are essential for the emergency physician. This is the 12th article in a continuing series of "off-service" goals and objectives. It outlines a mechanism for conveying important points of Emergency Medicine Administration to the EM III resident. The article includes materials describing the Administrative Content, Goals and Objectives, Key Contact System, and Contents of the EM Administrative briefcase. This information should assist faculty charged with the development or revision of the Administrative literature review and experiential block rotation in an emergency medicine residency. PMID- 1607632 TI - On death and dying in the emergency department. PMID- 1607633 TI - Burned. PMID- 1607634 TI - Light and electron microscopic studies of cellular localization of oPL with monoclonal and polyclonal antibodies. AB - Accurate knowledge of placental lactogen localization is fundamental to any hypothesis of its synthesis and secretion. We used locally generated monoclonal and polyclonal antibodies from three separate sources to localize ovine placental lactogen immunoreactivity on light and electron microscope Lowicryl K4M sections of ovine placentomes of 97-145 days of gestation, using immunogold techniques. All antibodies demonstrated that immunoreactivity was exclusively localized in the trophoectoderm binucleate cell Golgi body and granules and in granules in the syncytium derived from binucleate cell migration. No evidence was found to support a recent claim that monoclonal antibodies to oPL that were produced in Canada indicated a predominant localization of ovine placental lactogen to uninucleate trophectodermal cells. PMID- 1607635 TI - Distribution of the collagen binding heat-shock protein in chicken tissues. AB - We examined the tissue distribution of heat-shock protein MW 47,000 D, hsp47, which binds to native and denatured collagen including Types I, III, and IV, in various chicken tissues by Western blotting and immunohistochemical methods. hsp47 was located on fibrocytes or fibroblasts in the connective tissue in various organs, chondrocytes in the cartilage, smooth muscle cells in the gastrointestinal tract and blood vessels, vitamin A storage cells in sinusoidal area of liver, endothelial cells in blood vessels, and epithelial cells of renal glomeruli, tubules, and basal layer of epidermis. These cells also co-expressed a certain type of collagen molecule. Furthermore, in developing embryos, fibroblasts and chondrocytes expressed hsp47 before the deposition of collagen Type I or Type II in the surrounding tissue. These results indicate that the binding of hsp47 to collagen molecules has important biological significance. PMID- 1607636 TI - Localization of a carbohydrate antigen associated with growing oocytes and ovarian surface epithelium. AB - We used a monoclonal antibody (PS1) to a carbohydrate antigen to study the development of the oocyte and follicle during early stages of differentiation in several mammalian species. This antigen has been shown to localize within the cytoplasm of oocytes in primordial follicles as well as in growing oocytes. It is also localized within distinct layers of the zona pellucida (ZP) of developing follicles. Although this antibody was made against a specific ZP glycoprotein, the antigen also appears to be abundant in cells of the ovarian surface epithelium (OSE). The localization of this carbohydrate moiety has been observed in ovaries of rabbits of different ages as well as in the ovarian surface epithelium of other mammalian species including cat, cynomolgus monkey, baboon, and human. These studies demonstrate that there is an abundant carbohydrate antigenic determinant which is associated with both the mammalian oocyte and the ovarian surface epithelium but which is not apparent in other ovarian cell types or in non-ovarian secretory epithelium. This antibody probe should provide a valuable tool for studying the development and differentiation of the ovary, since this antigen is associated with two highly differentiated but distinct cell types. PMID- 1607637 TI - p53 overexpression in formalin-fixed, paraffin-embedded tissue detected by immunohistochemistry. AB - Mutation and overexpression of the p53 gene have been noted in a wide range of human cancers and are thought to play a role in malignant transformation. Previously, immunohistochemical detection of p53 has been possible only in fresh frozen tissues. We examined p53 expression in paraffin-embedded tissues from 50 epithelial ovarian cancers and 25 primary breast cancers with a modified immunohistochemical (IHC) technique developed in this laboratory, using monoclonal antibody (MAb) PAb1801. The 75 cases were selected from a group of patients in whom the expression levels had already been assessed in a fresh tissue IHC assay. An identical staining reactivity was observed in both formalin fixed, paraffin-embedded tissue and fresh-frozen tissue in 48 of 50 (96%) epithelial ovarian cancers and in 23 of 25 (92%) primary breast cancers. Immunodetection of p53 in paraffin-embedded tissue blocks will be a useful alternative to the standard fresh-tissue assay and can accurately reflect the level of p53 expression in human tumors. PMID- 1607638 TI - Chromosomal localization of transfected genes by a combination of hot banding and fluorescence in situ hybridization. AB - We describe the combination of hot banding with fluorescence in situ hybridization as a rapid and efficient method to identify integration sites of transfected DNA sequences in chromosomes. As a test system we used SW480 EJ2, a clonal cell line obtained after transfection of SW480 with pSV2neoEJ, a plasmid containing a point-mutated, c-Ha-RAS oncogene. Nick-translated probes were compared with random primed-labeled probes to evaluate their relative efficiency in fluorescence in situ hybridization. The fluorescence signals were quantified in interphase nuclei by confocal scanning laser microscopy. Nick-translated probes were found to yield better results. Hot banding followed by fluorescence in situ hybridization localized the integration site of pSV2neoEJ in SW480 EJ2 at the site of a translocation on a marker chromosome Xp+. The combination of fluorescence in situ hybridization and hot banding can be used to (a) rapidly and efficiently analyze integration sites in large numbers of transfectants, (b) assess the clonality of transfected cell lines, and (c) localize the site of integration of transfected genes in the recipient genome. PMID- 1607639 TI - On reviewing glycoconjugates. PMID- 1607640 TI - Immunohistochemistry and in situ hybridization of P-45017 alpha (17 alpha hydroxylase/17,20-lyase). AB - Cytochrome P-45017 alpha catalyzes both 17 alpha-hydroxylation and 17,20-side chain cleavage in steroidogenesis and lies at a key branch point in the pathways of steroid hormone biosynthesis. To obtain information on the precise localization of P-45017 alpha in swine testis, ovary, and adrenal, we undertook the simultaneous detection of P-45017 alpha mRNA and protein by combining immunohistochemistry with in situ hybridization. In situ hybridization was performed on 4% paraformaldehyde-fixed, paraffin-embedded sections by employing either a 39-base oligomer or a cDNA insert (1.7 KB) of porcine testis P-45017 alpha as DNA probe. Immunohistochemical study was performed by employing anti-P 45017 alpha. Hybridization signals were obtained in Leydig cells of the testis, theca interna of the ovarian follicle, and zona fasciculata reticularis cells of the adrenal cortex. Oligonucleotide probing yielded lower background signal than the cDNA probe. No specific signals were obtained in seminiferous tubules of the testis, medulla, and zona glomerulosa of the adrenal, and in membrana granulosa and interstitial cells of the ovary. Hybridization signals were obtained in the cells where immunoreactivity of the enzyme was observed by immunohistochemistry, except for some Leydig cells of the testis and theca interna cells of the ovary in which only immunoreactivity but not hybridization signal was observed. The present study provided detailed information about the precise cellular localization of P-45017 alpha expression at both the protein and mRNA levels in swine adrenal glands and gonads. This approach of simultaneous immunohistochemistry and in situ hybridization analysis of steroidogenic enzymes can be applied in the future to tissues exhibiting abnormal steroid metabolism and should contribute to a better understanding of steroidogenesis. PMID- 1607641 TI - Subdomains of the rough endoplasmic reticulum in colon goblet cells of the rat: lectin-cytochemical characterization. AB - Using lectin binding, we characterized subdomains of the rough endoplasmic reticulum (rER) in goblet cells of the rat colon. In this cell type, special rER regions can be differentiated on the basis of their content of low electron density and dilated cisternal spaces in conventional transmission electron microscopic preparations. The fine fibrillar content of these cisternal regions demonstrated high-affinity binding with lectins from wheat germ, Helix pomatia, Griffonia simplicifolia I-A4 and -B4, and Ricinus communis I, although not with the sialic acid-specific Limax flavus lectin and the fucose-binding Ulex europaeus I lectin. Sugar-inhibitory experiments indicated that glycoconjugates packed within these regions bound the lectins with higher affinity than molecules present in the Golgi apparatus and secretory granules. Furthermore, the lectin binding patterns of the rER subdomains differed from those of the Golgi apparatus and mucin granules: the terminal sugar residues sialic acid and fucose were demonstrable in the Golgi apparatus and mucin granules and were absent from the rER, while galactose-recognizing lectins bound intensely at these rER regions, weakly to Golgi elements, and were almost absent from mucin granules. PMID- 1607642 TI - AMP deaminase histochemical activity and immunofluorescent isozyme localization in rat skeletal muscle. AB - The cellular distribution of AMP deaminase (AMPda) isozymes was documented for rat soleus and plantaris muscles, utilizing immunofluorescence microscopy and immunoprecipitation methods. AMPda is a ubiquitous enzyme existing as three distinct isozymes, A, B and C, which were initially purified from skeletal muscle, liver (and kidney), and heart, respectively. AMPda-A is primarily concentrated subsarcolemmally and intermyofibrillarly within muscle cells, while isozymes B and C are concentrated within non-myofiber elements of muscle tissue. AMPda-B is principally associated with connective tissues surrounding neural elements and the muscle spindle capsule, and AMPda-C is predominantly associated with circulatory elements, such as arterial and venous walls, capillary endothelium, and red blood cells. These specific localizations, combined with documented differences in kinetic properties, suggest multiple functional roles for the AMPda isozymes or temporal segregation of similar AMPda functions. Linkage of the AMPda substrate with adenosine production pathways at the AMP level and the localization of isozyme-C in vascular tissue suggest a regulatory role in the microcirculation. PMID- 1607643 TI - Accurate determination of the time of cell birth using a sequential labeling technique with [3H]-thymidine and bromodeoxyuridine ("window labeling"). AB - During tissue embryogenesis, precursor cells divide actively and eventually withdraw from the mitotic cycle before differentiation. Accurate information about the time of terminal mitosis ("birthdate") of precursors is of vital importance for studying relationships between cell proliferation and differentiation. Methods presently available for birthdate determination, based on "pulse" or "cumulative" labeling with either tritiated thymidine (3HT) or bromodeoxyuridine (BrDU) incorporated into DNA during the mitotic cycle, allow only the approximate timing of terminal mitosis. To overcome this limitation, we have developed a "window labeling" technique based on the sequential administration of 3HT and BrDU. Chick retinal precursor cell cultures were first exposed to 3HT and, after a specified time interval, also to BrDU. After 6 days the cultures were fixed and processed for BrDU immunocytochemistry and 3HT autoradiography. Three populations of cells could be easily identified: (a) unlabeled cells, representing post-mitotic cells before label exposure; (b) BrDU labeled cells [either 3HT (+)/BrDU (+) or 3HT (-)/BrDU (+)], representing those that continue dividing after the addition of BrDU; and (c) "window-labeled" cells, 3HT (+)/BrDU (-), which are those undergoing their last round of DNA synthesis during the interval between 3HT and BrDU administration. Control experiments demonstrated that this method allows birthdate determinations with a resolution of hours or minutes and is essentially free of deleterious effects on precursor cell survival and differentiation. PMID- 1607644 TI - Subcellular visualization of light microscopic specimens by laser scanning microscopy and computer analysis: a new application of image analysis. AB - To identify subcellular organelles or to observe their pathological changes in sections prepared for light microscopy, immuno- and/or enzyme histochemical staining for the marker substances or enzymes of those subcellular organelles are frequently employed. With conventional light microscopes (CLM), however, it is hardly possible to determine whether or not the target organelles are properly stained and to confirm their fine structure. In the present study, the laser scanning microscope (LSM) was employed to obtain highly contrasted images of histochemically stained subcellular organelles at the limit of resolution in light microscopy. To refine or characterize those images, images built up as electronic signals in LSM were further processed in the Image Analysis System (IAS) with pipeline. Thus, the approximate figures of subcellular organelles such as microtubules, endoplasmic reticula, secretory granules, and mitochondria were visualized in brightfield on sections prepared for light microscopy (paraffin, frozen sections and cultured living cells). The validity of the images obtained by LSM or LSM-IAS was confirmed by immunoelectron microscopy when possible. The LSM images of histochemically stained suborganelles of various cells were definitely improved (refined and/or strengthened) by processing them with IAS. PMID- 1607645 TI - Ultrastructural non-radioactive in situ hybridization of GH mRNA in rat pituitary gland: pre-embedding vs ultra-thin frozen sections vs post-embedding. AB - In situ hybridization at the ultrastructural level can be carried out using three different methods: on vibratome sections before embedding in epoxy resin, on ultra-thin frozen sections, or on ultra-thin sections of tissues embedded in hydrophilic resin such as Lowicryl. With the purpose of comparing the sensitivity, resolution, and ultrastructural preservation of these three methods, we examined the expression of the growth hormone (GH) gene in anterior pituitary cells by in situ hybridization at the ultrastructural level, using a synthetic oligonucleotide complementary to the codons of the mRNA from Gln 45 to Ser 54 labeled at the 3' end of biotin-21dUTP. All these methods gave similar results: mRNA was located on the lamellar endoplasmic reticulum of somatotrophs. The pre embedding method gave the best ultrastructural preservation, with low resolution with the enzymatic detection system and an intermediate sensitivity. A probe concentration of 10 pmol/ml was sufficient to obtain a signal. With this method gold particles could not be used without pre-treatment. The frozen section method gave the best sensitivity (a signal was observed with 4 pmol/ml of probe) but the lowest ultrastructural preservation. On ultra-thin Lowicryl sections, resolution was as high as with the frozen-section method, ultrastructural conservation was intermediate, and sensitivity was low. These results indicate that the last method seems to be a good compromise between sensitivity and ultrastructural preservation. PMID- 1607646 TI - Poor reliability of immunocytochemical localization of IgG in immersion-fixed tissue from the central nervous system. AB - The effect of fixation technique and post mortem-to-fixation interval in immersion-fixed tissue from the central nervous system on immunocytochemical staining for the presence of an immunoglobulin was determined in mice. Immersion fixed tissue was found to be inferior to perfusion-fixed tissue for immunocytochemical staining of this serum protein. Unlike what has been observed for other antigens, the quality of staining for IgG in immersion-fixed tissue decreased to unacceptable levels if the post mortem-to-fixation interval was increased to more than a few hours. This effect may be secondary to the rapid post-mortem disintegration of the blood-brain barrier and a resulting diffusion of serum proteins into surrounding tissue from the vasculature. PMID- 1607647 TI - Chromogranin A in neurons of the rat cerebellum and spinal cord: quantification and sites of expression. AB - Chromogranin A (CGA) is an abundant protein of dense-cored secretory vesicles in endocrine and neuronal cells. The present study, for the first time, compares CGA of neurons of the central nervous system with the CGA of adrenal origin. By S1 nucleus protection assay, we found that the 3' part of the CGA mRNA between exons 5-8 of the cerebellum and the spinal cord of the rat is homologous to that of the adrenal. In situ hybridization histochemistry revealed that CGA mRNA in the cerebellar cortex is present in cell bodies of Purkinje cells and in neurons of the deep cerebellar nuclei. The perikarya of these cells also exhibit CGA-like immunoreactivity. CGA mRNA and CGA-like immunoreactivity are also present in the motoneurons of the ventral, lateral, and dorsal horns of the rat spinal cord. The amounts of CGA, as determined by radioimmunoassay in cerebellum and spinal cord, were about one tenth of the amounts detected in the adrenal, adenohypophysis, or the olfactory bulb. The sites of CGA expression suggest that CGA may be involved in signal transduction in the motor system. PMID- 1607648 TI - Comparative stabilities in vitro and in vivo of a recombinant mouse antibody FvCys fragment and a bisFvCys conjugate. AB - A murine antibody FvCys fragment with a single additional cysteine residue at the C terminus of the VH domain was expressed in Escherichia coli from a modified expression plasmid containing the structural genes for the VH and VL domains derived from the anti-lysozyme hybridoma D1.3. Chemical cross-linking between the introduced sulfhydryl groups of two FvCys fragments by means of bis maleimidohexane was used to generate a bisFvCys conjugate. The stability of the bisFvCys conjugate and an FvCys analogue that had been reacted with N-ethyl maleimide to block the free sulfhydryl group, FvCys(BL), were compared after 125I labeling. The bisFvCys conjugate was completely stable to incubation in solution at 37 degrees C for 24 h whereas only 60% of the FvCys(BL) fragment remained soluble. After i.v. administration to normal Wistar rats, both Fv proteins were rapidly cleared from the circulation with biphasic kinetics that were best fitted to a two-compartment open pharmacokinetic model. The alpha-phase half-life of the bisFvCys conjugate, 0.32 h, was significantly longer than that of the FvCys(BL) fragment, 0.15 h (p less than 0.001) whereas there was no significant difference between the beta-phase half-lives, 1.4 to 1.6h. No chain cleavage or covalent attachment to serum protein was detected by SDS-PAGE analysis of serum samples. However, gel permeation HPLC revealed that both Fv proteins associated with serum proteins in vivo and in vitro. PMID- 1607649 TI - Effect of H chain V region on complement activation by immobilized immune complexes. AB - Activation of C by immune complexes (IC) in tissues and the inflammatory consequences are major determinants in the pathogenesis of many autoimmune disorders. To assess the factors involved in C activation by such IC, we examined the binding of C components by chimeric IgG1 antibodies bound to immobilized Ag. We previously reported that alterations in the H chain V regions can affect the binding of first component of C (C1q) and a major breakdown product of the third C component (C3b) when otherwise identical antibodies were bound to immobilized (Tyr, Glu)-Ala-Lys. To evaluate C activation of these antibodies in well defined IC, we utilized a 9-amino acid peptide conjugated to BSA as Ag. The peptide:BSA conjugate was bound similarly by the two IgG1 antibodies which differed mainly in the CDR3 regions, but also in 9 other amino acids in the H chain V region. When soluble IC were prepared with the two antibodies, they activated C similarly. However, C activation by solid phase Ag:antibody complexes differed; we found that antibody 10B bound more C1q and C3b than antibody B11 did, unless the Ag was present at high density on the plates. These data suggest that the variable region differences affect C activation by these antibody when they are bound to immobilized Ag. Furthermore, these results underscore the differences in C activation by the same antibody depending upon whether the IC are free in solution or immobilized. PMID- 1607650 TI - Species specificity in the interaction of CD8 with the alpha 3 domain of MHC class I molecules. AB - The alpha 1 and alpha 2 domains of the class I MHC molecule constitute the putative binding site for processed peptides and the TCR, although the alpha 3 domain has been implicated as a binding site for the CD8 molecule. Species specificity in the binding of CD8 to the alpha 3 domain has been suggested as an explanation for the low xenogeneic T cell response to class I molecules, but results on this point have been conflicting and controversial. We have addressed this issue using CTL lines from HLA-A2.1 transgenic mice that specifically recognize and lyse A2.1-expressing cells infected with influenza A/PR/8 or pulsed with influenza matrix peptide M1(57-68). Species specificity was examined using transfectants that expressed hybrid molecules containing the alpha 1 and alpha 2 domains from HLA-A2.1 and the alpha 3 domain from a murine class I molecule. Lower levels of M1(57-68) peptide were required to sensitize L cell transfectants expressing a chimera that contained an H-2Dd alpha 3 domain than targets expressing the intact A2.1 molecule. However, at high doses of peptide, lysis of these two targets was similar. However, no reproducible difference in sensitization was observed using EL4 or Jurkat transfectants expressing A2.1 or A2.1 chimeric molecules that contained an H-2Kb alpha 3 domain. In all cases, however, lysis of peptide-pulsed A2.1 expressing targets was more sensitive to inhibition with anti-CD8 mAb than lysis of cells expressing these chimeric molecules. Thus, under suboptimal conditions such as low Ag density or in the presence of anti-CD8 mAb, these CTL preferentially recognize class I molecules with a murine alpha 3 domain. This suggests that there is some species specificity in the interaction of CD8 with the alpha 3 domain of the class I molecule. However, CTL recognition was inhibited by point mutations in the alpha 3 domain of HLA-A2.1 that have been shown to inhibit binding of human CD8 and recognition by human CTL, suggesting that murine CD8 interacts to some degree with human alpha 3 domains, and that similar alpha 3 domain residues may be important for murine and human CD8 binding. The relevance of these results to an understanding of low xenogeneic responses is discussed. PMID- 1607651 TI - Substituted isocoumarins as inhibitors of complement serine proteases. AB - Inhibition of complement proteins D, B, C2, C1s, C1r, I, and the catalytic fragments Bb and C2a by substituted isocoumarins was investigated. 3,4 Dichloroisocoumarin, a general serine protease inhibitor, inhibited factor D, C1r, and C1s moderately with second-order inhibition constants (kobs/[I]) of 40 to 190 M-1 s-1, but it did not inhibit C2, factor B, C2a, or Bb. The best inhibitor for factors D and B was 4-chloro-7-guanidino-3-methoxyisocoumarin with kobs/[I] values of 250 and 290 M-1 s-1, respectively. Most isocoumarins did not inhibit C2 or C2a; only 4-chloro-3-isothiureidoalkoxyisocoumarins were slightly inhibitory. 3-Alkoxy-4-chloro-7-guanidinoisocoumarins inhibited C1r and C1s moderately. The best inhibitor for C1r and C1s was 4-chloro-3-(3 isothiureidopropoxy)isocoumarin with kobs/[I] values of 6,600 and 130,000 M-1 s 1, respectively. Fifty amino acid or peptide thioesters containing Arg or other amino acids at the P1 site were tested as substrates of factor I, however none was hydrolyzed. Isocoumarins substituted with chloro and basic groups such as guanidino and isothiureidoalkoxy inhibited factor I activity with its natural substrate C3b, but kobs/[I] values were low. 4-Chloro-3-ethoxy-7 guanidinoisocoumarin inhibited activation of the alternative pathway and, to a lesser extent, of the classical pathway in serum. Several other substituted isocoumarins also inhibited cobra venom factor-initiated activation of the alternative pathway in serum. PMID- 1607652 TI - IL-4 inhibits macrophage-mediated killing of Plasmodium falciparum in vitro. A possible parasite-immune evasion mechanism. AB - Although a number of mechanisms have been put forward for immunity to malaria, their importance remains to be clarified. One of the important findings is that nonactivated monocytes and macrophages showed marked antiplasmodial activity in vitro. Recently we postulated that parasites may induce host factors that may depress the natural antiplasmodial activity of monocytes. In this investigation we identify IL-4 as a lymphokine that could function in this capacity. Human monocytes and macrophages in the absence of antiplasmodial antibody showed substantial killing of the asexual erythrocytic forms of Plasmodium falciparum as determined by a radiometric assay. Suppression of this killing was seen if the mononuclear phagocytes were pretreated with human rIL-4 at concentrations of 10 to 250 U with optimum activity between 100 and 250 U/2 x 10(5) cells. Cells from some individuals were rendered completely inactive by the IL-4 treatment. In contrast, IL-4 did not affect the neutrophil-mediated anti-P. falciparum activity. Our work identifies a potentially important parasite immune evasion mechanism involving IL-4 suppression of macrophage antiparasite activity. PMID- 1607653 TI - Plasma lipopolysaccharide (LPS)-binding protein. A key component in macrophage recognition of gram-negative LPS. AB - LPS-binding protein (LBP) binds with high affinity (Kd approximately equal to 10( 9) M) to lipid A of LPS isolated from rough (R)- or smooth (S)-form Gram-negative bacteria as well as to lipid A partial structures such as precursor IVA. To define the role of LBP in regulating responses to LPS we have examined TNF release in rabbit peritoneal exudate macrophages (M phi) stimulated with LPS or with complete or partial lipid A preparations in the presence or absence of LBP. In the presence of LBP, M phi showed increased sensitivity to S- and R-form LPS as well as synthetic lipid A. Compared with LPS or lipid A, up to 1000-fold greater concentrations of partial lipid A structures were required to induce TNF production. However, consistent with our previous observations that these structures bind to LBP, TNF production was increased in the presence of LBP. In contrast, LBP did not enhance or inhibit TNF production produced by heat-killed Staphylococcus aureus, peptidoglycan isolated from S. aureus cell walls, or PMA. Potentiated M phi responsiveness to LPS was observed with as little as 1 ng LBP/ml. Heat-denatured LBP (which no longer binds LPS), BPI (an homologous LPS binding protein isolated from neutrophils), or other serum proteins were without effect. LBP-treated M phi also showed a more rapid induction of cytokine mRNA (TNF and IL-1 beta), higher steady-state mRNA levels and increased TNF mRNA stability. These data provide additional evidence that LBP is part of a highly specific recognition system controlling M phi responses to LPS. The effects of LBP are lipid A dependent and importantly, extend to LPS preparations isolated from bacteria of R- and S-form phenotype. PMID- 1607654 TI - Presentation of three different viral peptides, HTLV-1 Tax, HCMV gB, and influenza virus M1, is determined by common structural features of the HLA-A2.1 molecule. AB - To determine whether similar or dissimilar molecular features of class I molecules are involved in the presentation of structurally distinct peptides, we have investigated the influence of different pockets of the HLA-A2.1 molecule on the presentation of three different viral peptides. HTLV-I Tax peptide 12-19, HCMV gB 619-628, and influenza M1 58-66 are minimal peptides that induce HLA-A2.1 restricted noncross-reactive CTL. A detailed analysis of the structural features of HLA-A2.1 that are involved in peptide presentation was undertaken using a panel of 11 HLA-A2 mutants with single amino acid substitutions within pockets present in the peptide binding site. Nine of the 11 mutants affected presentation of each of the three peptides, whereas the other two mutants had negative effects on presentation of only two of these viral peptides. These results indicate that common structural features in HLA-A2 determine the binding of different peptides, and help to provide a plausible explanation for how structurally diverse peptides bind to HLA-A2. PMID- 1607655 TI - Predominance of VH-D-JH junctions occurring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies. AB - Sequence diversity at the junctions of Ig genes differs between newborn and adult mice in two respects: 1) fetal/newborn Ig lack N regions; and 2) these N- junctional sequences very often contain 1 to 6 nucleotides that could have been encoded by either of the two joined gene segments. We address the hypothesis that such short homologies preferentially direct recombination to that site, and we analyze the effect of such homology-directed recombination upon the neonatal Ig repertoire. We examined 546 CDR3 sequences that were generated from polymerase chain reaction-amplified DNA from fetal and newborn liver using primers from three different VH families: S107, 7183, and J558. All junctional sequences using 14 frequently occurring IgH V-D and D-J gene combinations were analyzed. In 12 of the 14 combinations analyzed, there were 1 to 3 short sequence homologies, and the junctional sequences that would be created by those homologies were observed with high frequency. The D-J junctions often had two to three predominant junctional sequences, whereas the V-D junctions had one dominant junctional sequence. The only exceptions were the VHJ558-D junctions, where homology directed recombination using the sequence homology between VHJ558 genes and most D genes would result in an out-of-frame join, and most of our sequences were productive. This latter result further suggests that homology-directed recombination may play a role in the nonrandom VH gene usage observed in fetal and newborn mice. Thus, most neonatal IgH junctions show limited diversity, not only due to the lack of N regions, but also because of nonrandom junctional sequences. Inasmuch as the few adult N- junctions also show a high frequency of homology-directed junctional sequences, V-D-J recombination throughout life may involve pairing via short homologies, with addition of N regions obscuring its role in the formation of adult IgH junctions. PMID- 1607656 TI - Constitutive monocyte-restricted activity of NF-M, a nuclear factor that binds to a C/EBP motif. AB - In a search for monocyte-specific nuclear factors, we analyzed in human cells the promoter of the chicken myelomonocytic growth factor, a gene that, in the chicken, is expressed in myeloid and myelomonocytic cells. Reporter gene constructs were active in monocytic Mono Mac 6 cells and in monoblastic THP-1 cells but not in the hematopoietic stem cell line K562. When a region with homology to the sequence recognized by CAAT enhancer-binding proteins (C/EBP) was inactivated by site-directed mutagenesis, the reporter activity was reduced by a factor of 10. Multimers of this region, termed F, in front of a heterologous promoter were active in Mono Mac 6 and THP-1 cells but not in K562 cells, WIL2 B cells, BT20 mammary carcinoma cells, MelJuso melanoma cells, or SK-Hep-1 hepatoma cells. Gel shift analysis with the F oligonucleotide identified DNA-binding activity in monocytic Mono Mac 6, monoblastic THP-1, and myelomonocytic HL60 cells. No binding was detected in myelomonocytic RC2A cells, in myeloid KG-1 cells, or in the hematopoietic stem cell line K562. Furthermore, a panel of solid tumor cell lines, representing various tissues, were also negative. Stimulation by PMA could not induce this binding factor in any of the negative cell lines. Analysis of primary cells (granulocytes, T cells, monocytes, and alveolar macrophages) revealed binding activity only in monocytes and macrophages. This DNA-binding factor, termed NF-M, was found to consist of two molecules, of 50 and 72 kDa, as determined by affinity cross-linking. Binding of NF-M was competed by the region F oligonucleotide and by the C/EBP motif from the albumin enhancer but not by an AP-2 motif. These data suggest that NF-M is a member of the C/EBP family of nuclear factors. The monocyte-restricted activity of NF-M suggests that this nuclear factor may be involved in regulation of monocyte-specific genes. PMID- 1607657 TI - Transcription of unrearranged Ig H chain genes in human B cell malignancies. Biased expression of genes encoded within the first duplication unit of the Ig H chain locus. AB - Analysis of the H chain class switch recombination events on the productive and nonproductive alleles of several human B cell lines has demonstrated that, in the majority of cases, the two loci had rearranged different CH genes. The absence of a strict correlation between the two rearrangement events has been interpreted in favor of a stochastic switching mechanism in human B cells. Based on the accessibility model for the H chain class switch, we have considered an alternative explanation, namely, that transcriptional activation of more than one CH gene could render more than one isotype accessible for recombination. In order to test this possibility, we have stimulated a number of IgM-bearing B cell tumors and analyzed the transcriptional response of their unrearranged C gamma and C alpha H chain genes at the Ig class level by Northern hybridization and at the subclass level by RNA-RNA solution hybridization. Our data show that human clonal B cell populations can simultaneously express germ-line transcripts of both gamma and alpha genes. Our data also demonstrate a bias in the expression of the different isotypes in the B cell chronic lymphocytic leukemias analyzed, with the genes present with the first duplication unit of the H chain locus (gamma 3, gamma 1, and alpha 1) being expressed almost exclusively. These findings indicate that transcriptional activation of large chromosomal regions containing more than one CH gene could render all the genes available for recombination and, therefore, provide an explanation for the asymmetry in the rearrangement events that have previously been described in human B cell tumors. The possible relevance of our findings to the molecular mechanism of the H chain class switch is discussed. PMID- 1607658 TI - Augmentation of in vivo cytotoxic T lymphocyte activity and reduction of tumor growth by large multivalent immunogen. AB - Class I alloantigen incorporated into cell-size supported membranes provides an effective stimulus for in vitro stimulation of CTL responses. When alloantigen bearing cell-size (5 microns) microspheres, termed large multivalent immunogen (LMI), were administered in vivo, no primary cytotoxic response to the Ag could be detected. However, coadministration of LMI and allogeneic tumor stimulator cells resulted in substantial augmentation of the resulting CTL response, compared with that obtained from mice that received just stimulator cells. Responses were augmented only when the same alloantigen was present on the LMI and on the stimulator cells, and the effector cells remained specific for the cognate alloantigen-bearing targets. The physical form of the alloantigen was critical for augmentation; alloantigen in liposomes had no effect on response levels. Tumor cell Ag in the form of purified plasma membrane vesicles can also be incorporated onto the surface of cell-size microspheres. As with allogeneic responses, tumor Ag on LMI specifically augmented the in vivo CTL activity generated in response to irradiated tumor cells in syngeneic mice. Administration of Ag-bearing LMI to mice inoculated i.p. with live P815, EL4, or RDM4 tumor cells resulted in a significant reduction in growth of the tumors in their syngeneic hosts. Similarly, LMI treatment significantly reduced growth of P815 as a solid s.c. tumor. LMI-mediated growth reduction occurred only when plasma membrane Ag from the cognate tumor was used to prepare the LMI, and Ag in the form of free plasma membrane vesicles was not effective. Although Ag has been used to manipulate in vivo humoral and Th responses, this has proven to be much more difficult for CTL responses. The ability of Ag-bearing LMI to affect significantly the in vivo levels of cytolytic response and to reduce syngeneic tumor growth has potential for application to tumor immunotherapy and, possibly, treatment of other diseases in which CTL can provide a protective effect. PMID- 1607659 TI - R1-20, a novel monoclonal antibody reacting with a molecule distinct from integrin family, induces homotypic cell aggregation. AB - R1-20, a novel mAb reacting with a cell surface Ag on normal human lymphocytes and leukemic cell lines, was shown to induce homotypic cell aggregation in leukemic cell lines. This phenomenon was specific to mAb R1-20 because antibodies recognizing CD2, CD7, CD28, and HLA-ABC failed to exhibit homotypic cell aggregation. Induction of aggregation by mAb R1-20 occurred at 37 degrees C, but not at 4 degrees C and required cytoskeletal integrity. Sodium azide, a metabolic inhibitor, had no effect on the aggregation. Distinct from lymphocyte function associated Ag-1/intercellular adhesion molecule-1 interaction in which divalent cations are essential elements, R1-20-mediated aggregation was not abolished with EDTA treatment. The R1-20 Ag was determined as a molecule of M(r) 100 to 110 kDa in immunoprecipitation and immunoblotting methods, under both reducing and nonreducing conditions. The molecular composition is quite different from that of any known integrin molecule. The R1-20 Ag was expressed on resting and activated T Lymphocytes as well as on normal B lymphocytes. Monocytes and granulocytes had no detectable R1-20 Ag. Among the leukemia-derived cell lines we used, mAb R1-20 reacted with 18 of 32 T cell lines, 2 of 20 B cell lines, 2 of 3 non-T-non-B cell lines, 2 of 7 myelomonocytic cell lines, and 2 of 3 nonlymphoid-nonmyeloid cell lines. All EBV-transformed B cell lines examined (10 cell lines) were R1-20+. The spectrum of reactivity among the cell lines tested was different from that of known antiadhesion antibodies tested. All these findings indicate that the Ag recognized by mAb R1-20 may represent a new type of cell adhesion molecule. PMID- 1607660 TI - Enhancement of human neutrophil functions by a monoclonal antibody directed against a 19-kDa antigen. AB - A mouse IgG mAb termed P1C3 was raised against A23187-treated human peripheral blood neutrophils and has been shown to recognize an Ag with an apparent molecular mass of 19 kDa, herein named p19. This p19 Ag was weakly expressed at the cell surface of resting human peripheral blood neutrophils and monocytes, but its cell surface expression was dramatically increased upon activation of these cell types with different secretagogues, including FMLP, PMA, and the calcium ionophores A23187 and ionomycin. A large latent pool of p19 molecules became accessible by immunofluorescence flow cytometry after cell permeabilization of resting neutrophils. A practically total translocation of the intracellular pool of this p19 molecule to the plasma membrane was achieved under appropriate cell stimulation, which induced an almost total degranulation of neutrophil secretory granules. The p19 Ag was absent from platelets, PBL, as well as from the human promyelocytic cell line HL-60, the human promonocytic cell line U937, and the human lymphoid cell lines Daudi and Jurkat. The p19 Ag was also expressed by circulating and/or interstitial neutrophils and monocytes in distinct tissues examined. The mAb P1C3 was found to enhance several neutrophil responses, such as chemotaxis, cell adhesion, phagocytosis, and respiratory burst. These data indicate that the mAb P1C3 recognizes an intracellular Ag in human resting mature neutrophils and monocytes, which upon cell activation is translocated to the cell surface and is able to affect cell functionality. PMID- 1607661 TI - Failed self-tolerance and autoimmunity in IgG anti-DNA transgenic mice. AB - Transgenic mice were generated that express both the H and L chain genes derived from a hybridoma secreting an IgG2a mAb specific for ds- and ssDNA. This hybridoma is derived from a lupus mouse and can accelerate nephritis in young NZB x NZW F1 female mice and induce clinical nephritis in BALB/c mice. Some transgenic B cells did not exhibit allelic exclusion; they expressed both transgene-derived IgG and endogenous IgM intracellularly. Most of the B cells in transgenic mice expressed endogenous IgM, some of them expressed low levels of IgG on cell membranes. The transgenic mice, created in a strain not prone to SLE, expressed elevated serum IgG anti-DNA, and some developed clinical nephritis. The affinity of the spontaneously secreted IgG antibodies for dsDNA were similar in nephritic NZB x NZW F1 and transgenic mice. In contrast to the nontransgenic littermates, immunization of transgenic mice with murine DNA further enhanced serum levels of IgG anti-DNA in transgenic mice. Therefore, expression of transgene-encoded IgG anti-DNA mainly in the secreted form does not provide the signals necessary for allelic exclusion or self-tolerance. Expression of this Ig is sufficient to induce a mild form of autoimmune disease. PMID- 1607662 TI - Induction of a cellular immune response to a foreign antigen by a recombinant Listeria monocytogenes vaccine. AB - A recombinant strain of Listeria monocytogenes that stably and constitutively expresses Escherichia coli beta-galactosidase was used as a live vaccine vector. BALB/c mice were immunized orally or parenterally with the recombinant L. monocytogenes, and their cellular and humoral immune responses to beta galactosidase were measured. Spleen cells taken 1 week after oral inoculation or 5 weeks after oral or parenteral inoculation (with a boost at 4 weeks) showed beta-galactosidase-specific CTL responses. The CTL line derived from mice immunized i.p. was also shown to be class I restricted and Thy-1.2+, CD8+, and TCR alpha beta+. All mice immunized with the recombinant L. monocytogenes had positive delayed-type hypersensitivity responses to heat-killed L. monocytogenes, but only 15% had a positive delayed-type hypersensitivity reaction to beta galactosidase. Individual serum samples from mice immunized i.p. or i.v. were tested for antibody to beta-galactosidase. Approximately 11% had low positive titers for beta-galactosidase antibodies. These results demonstrate that both oral and parenteral immunization with recombinant L. monocytogenes results in a cellular immune response to the foreign protein, which is primarily a specific CD8+ CTL response. PMID- 1607663 TI - In vitro induction of CD8 expression on thymic pre-T cells. II. Characterization of CD3-CD4-CD8 alpha + cells generated in vitro by culturing CD25+CD3-CD4-CD8- thymocytes with T cell growth factor-beta and tumor necrosis factor-alpha. AB - We previously reported that CD25 (IL-2R p55)-positive CD3-CD4-CD8- murine thymocytes can be induced to express CD8 alpha (Lyt-2) by transforming growth factor-beta plus TNF-alpha in the presence of IL-7 (which is necessary to maintain the viability and differentiation capacity of CD25+CD3-CD4-CD8- thymocytes in vitro). The majority of cells recovered after 2 to 3 days from these cultures expressed CD8 alpha (but not CD3 or CD4). In this study, we have characterized these in vitro generated CD3-CD4-CD8 alpha + thymocytes and compared them with normal CD3-CD4-CD8+ thymocytes. Unlike normal CD3-CD4-CD8+ thymocytes that express CD8 alpha and CD8 beta (Lyt-3-chain) simultaneously, only a fraction of in vitro generated CD3-CD4-CD8 alpha + cells expressed CD8 beta. However, along with the induction of CD8 alpha and CD8 beta expression, the expression of other T cell differentiation markers (including CD2, CD25, and CD44) also changed in a manner corresponding to physiologic differentiation. Cell surface phenotyping suggests that CD8 alpha + beta - cells are less mature than CD8 alpha + beta + cells. These in vitro generated CD3-CD4-CD8 alpha + thymocytes expanded and differentiated into the CD4+CD8+ stage as well as mature (CD3+) single positive (CD4+CD8-) and CD4-CD8+) stages in fetal thymus organ culture that had been depleted of lymphoid cells by treatment with 2-deoxyguanosine. The latter observation indicates that these in vitro generated CD3-CD4-CD8 alpha + thymocytes are responsive to other differentiation-inducing signals (including those that induce CD4) that exist in fetal thymus organ culture. These results suggest that in vitro generated CD3-CD4-CD8 alpha + thymocytes represent intermediate differentiation stages between CD25+CD3-CD4-CD8- and CD3-CD4-CD8+ cells found in normal thymus. PMID- 1607664 TI - IL-2-induced signal transduction involves the activation of nuclear NF-kappa B expression. AB - Using electrophoretic mobility shift assays and DNA-protein cross-linking techniques, we demonstrate that IL-2 binding to functional forms of the human IL 2R activates nuclear expression of the eukaryotic transcription factor NF-kappa B. These inductive effects of IL-2 were observed in three different cellular systems including human Jurkat T cells stably transfected with IL-2R beta cDNA, mouse pro-B BA/F3 cells stably expressing human IL-2R beta chains either alone or in combination with human or murine IL-2R alpha chains, and purified primary resting human T cells constitutively displaying small numbers of IL-2R beta molecules. IL-2 activation of nuclear NF-kappa B expression is regulated in part at a post-translational level, involving the rapid translocation of both the 50- and 65-kDa subunits of NF-kappa B from the cytoplasm to the nucleus. However, IL 2 induction also produced an increase in mRNA for NF-kappa B p105, indicating an additional pretranslational component of regulation. In contrast, IL-2 exerts only minor effects on NF-kappa B p65 mRNA expression. IL-2 induction of NF-kappa B through the IL-2R beta subunit was both correlated with activation of the endogenous IL-2R alpha gene and critically dependent upon the presence of a serine-rich cytoplasmic domain within IL-2R beta (amino acid residues 267-312). This domain has previously been shown to be essential for IL-2-induced cell growth and may correspond to a binding site for an IL-2R beta-associated tyrosine kinase. Together, these findings suggest that NF-kappa B may play an important role as one intracellular second messenger relaying signals from the plasma membrane to cell nucleus that leads to IL-2-induced activation and growth. PMID- 1607665 TI - Identification and induction of keratinocyte-derived IL-10. AB - It has previously been demonstrated that the epidermis is a rich source of proinflammatory cytokines and growth factors and that complex interactions between these factors may affect inflammatory responses in skin. To investigate whether IL-10 (cytokine synthesis inhibitory factor) is part of this complex process, RNA was extracted from normal epidermis at various times after application of various chemicals to murine skin and mRNA signals for IL-10 were sought using a quantitative reverse-transcriptase-polymerase chain reaction technique. IL-10 signal strength was normalized to that of beta-actin in each sample. IL-10 mRNA signals were occasionally identified in normal epidermis but were uniformly enhanced 4 h after hapten application, and were maximal after 12 h. Contact allergens induced IL-10 mRNA signals whereas vehicles and irritants did not. Depletion of Langerhans cells, Thy-1+ dendritic epidermal cells, and T lymphocytes demonstrated that keratinocytes were the main source of IL-10 mRNA. IL-10 signals were also detected in mRNA derived from PAM 212 (spontaneously transformed keratinocyte) cells. IL-10 protein could be detected by immunoprecipitation, with an IL-10 mAB, of supernatants obtained 16 h after cultured epidermal cells were coupled with hapten. This study demonstrates that murine keratinocytes are capable of producing IL-10 mRNA and protein, and that signal strength of IL-10 mRNA is enhanced by hapten application. PMID- 1607666 TI - Comparative toxicity of the HD-1 and NRD-12 strains of Bacillus thuringiensis subsp. kurstaki to defoliating forest Lepidoptera. AB - Insecticidal activities of sporulated cultures of the HD-1 and NRD-12 strains of Bacillus thuringiensis subsp. kurstaki were compared against four species of defoliating forest lepidopterans in diet-incorporation assays. There was no difference in LC50 between the two strains to larvae of spruce budworm (Choristoneura fumiferana), gypsy moth (Lymantria dispar), eastern hemlock looper (Lambdina fiscellaria fiscellaria), and whitemarked tussock moth (Orgyia leucostigma), whether expressed as total alkaline soluble protein, activated toxin protein, or International Units as determined by bioassay against Trichoplusia ni. Both strains were consistently more toxic than HD-1-S-1980 when compared on the basis of alkali-soluble protein, but not on the basis of activated toxin or International Units. Hybridization of genomic DNA after restriction with HindIII revealed the presence of all three cryIA toxin genes in each of the isolates used in this study, including HD-1-S-1980, which was previously reported to have lost the cryIA(b) gene. PMID- 1607667 TI - Digestion of Bacillus thuringiensis var. israelensis spores by larvae of Aedes aegypti. AB - The larvicidal activity of Bacillus thuringiensis var. israelensis against mosquitoes and the blackfly is included in parasporal crystalline bodies which are produced during sporulation. Following ingestion, the crystals are solubilized in the larval midgut and induce death within a short time; the spores germinate in the dead larvae and complete a growth cycle. The fate of the spores in surviving live larvae was elucidated by using a nonlarvicidal B. thuringiensis var. israelensis mutant. When introduced as the only food source, spores of this mutant support development to the adult stage of newly hatched Aedes aegypti larvae at a rate directly related to spore concentration. The conclusion that spores of B. thuringiensis var. israelensis are digested in the larval gut was substantiated by following the incorporation of [35S]methionine-labeled spores into larval tissues. PMID- 1607668 TI - Phagocytosis by hemocytes of the hard clam, Mercenaria mercenaria. AB - Large granular hemocytes of Mercenaria mercenaria avidly phagocytose a variety of biological particles (red blood cells of six species, yeast, and gram-positive and gram-negative bacteria) as well as polystyrene spheres. Clam hemolymph is not necessary for phagocytosis but may have some opsonic effect in certain circumstances (e.g., low temperature and low particle density). Formaldehyde treatment of red blood cells enhances susceptibility to phagocytosis. Phagocytosis by Mercenaria hemocytes in vitro appears to be a nonspecific process. PMID- 1607669 TI - Agglutinins in the hemolymph of the hard clam, Mercenaria mercenaria. AB - Lectins in the serum of the clam Mercenaria mercenaria agglutinate some red blood cells, bacteria, and yeast. The interaction of these substances with particles is affected by sugars, ions, temperature, and alteration of particle surfaces. Lectins are not needed for phagocytosis of foreign particles in vitro. In M. mercenaria these recognition molecules do not enhance defense mechanisms. PMID- 1607670 TI - Transmission of the hereditary S character in Drosophila simulans: effects of aging and temperature treatments. AB - The expression of the S character of Drosophila simulans associated to hereditary reovirus DSV is affected by the rearing temperature. The transmission of the S character and the consequences of the length of high temperature (28 degrees C) treatments on that transmission were investigated. Larvae treated at 28 degrees C from eclosion to imaginal emergence produce few S individuals in the offspring. The offspring of larvae treated between the 144th hr of development (middle of the pupal stage) and the imaginal emergence show variable levels of S phenotype expression. These levels appear to be related to the age and phenotype of their mothers. Those facts are discussed under the hypothesis of S character being caused by the hereditary reovirus Drosophila S virus. PMID- 1607671 TI - A novel bioassay system for evaluating the toxicity of Bacillus thuringiensis israelensis against mosquito larvae. AB - A bioassay system employing acutely toxic concentrations of a spore-crystal mixture of Bacillus thuringiensis subspecies israelensis against fourth instar larvae of Aedes aegypti (L.) is described. Individual larvae are separately exposed to toxin in glass-lined miniature wells or scintillation vials. This method is free from the deaths due to predation among larvae. Such larval deaths are commonly encountered in bioassay groups of 25 larvae as currently specified in the World Health Organization guidelines. Our method offers shortened testing time, increased accuracy, and improved statistical precision. PMID- 1607672 TI - Digestibility by and pathogenicity of the protozoa Tetrahymena pyriformis to larvae of Aedes aegypti. PMID- 1607673 TI - Immunohistochemical distribution of adult T-cell leukemia-derived factor/thioredoxin in epithelial components of normal and pathologic human skin conditions. AB - Tissues from normal human skin and various skin diseases were studied with the immunoperoxidase technique using an antibody to adult T-cell leukemia-derived factor (ADF), a homologue of human thioredoxin. Normal human skin showed positive immunostaining for ADF/thioredoxin in the outer root sheath of hair follicle, sebaceous glands, and secreting components of apocrine and eccrine sweat units, but not in the unexposed interfollicular epidermis and other parts of both hair follicles and the sweat units. Immunoreactivity of benign skin tumors gave similar distribution to their normal counterparts; trichilemmal cyst, nevus sebaceus, senile sebaceous hyperplasia, and mixed cell tumor were positive for immunostaining, whereas epidermal cyst and pilomatricoma were not. No immunoreactivity was detected in malignant skin tumors such as basal cell carcinoma and poorly differentiated squamous cell carcinoma. Solar keratosis, well-differentiated squamous cell carcinoma, some of metastatic lesions of squamous cell carcinoma, and extramammary Paget's disease reacted with the antibody. These immunoreactivities reflected numerous functions of thioredoxin in higher organisms. Our findings suggest that the expression of ADF/thioredoxin in both normal and abnormal human skin is related to epithelial cell differentiation. PMID- 1607675 TI - Lamina densa malformation involved in histogenesis of primary localized cutaneous amyloidosis. AB - Skin lesions of lichenoid amyloidosis and macular amyloidosis were immunohistochemically investigated using five monoclonal antibodies against basement membrane zone (BMZ) components. A hemidesmosomal component did not contribute to amyloid deposits, but components of the lamina densa and anchoring fibrils were associated with amyloid deposits in the uppermost dermis. Immunoelectron microscopy revealed that these BMZ components were not only aggregated in the BMZ and dermis, but were also involved in the individual amyloid islets. The lamina densa was disrupted in the interface areas just above the amyloid deposits, where cytoplasm of the basal cells directly faced the aggregate of amyloid filaments. Aggregates of some BMZ components were continuous to the amyloid islets from the lamina densa area. These findings suggest that a lamina densa malformation is involved in amyloid production in the interface of the BMZ, and support the secretion theory rather than the fibrillar body theory of amyloidogenesis in these types of primary localized cutaneous amyloidosis. PMID- 1607674 TI - Topical delivery enhancement with multilamellar liposomes into pilosebaceous units: I. In vitro evaluation using fluorescent techniques with the hamster ear model. AB - Evidence suggesting liposomal delivery into the pilosebaceous unit of the male Syrian hamster ear membrane was found using two fluorescent techniques, quantitative fluorescence microscopy (QFM), and a scraping method where the various tissue strata of treated skin are analyzed using fluorescence spectrophotometry. Whole ears were mounted on Franz diffusion cells and treated for 24 h with 40 microliters of the following test formulations, each containing approximately 100 micrograms/ml carboxyfluorescein (CF): i) multilamellar phosphatidylcholine: cholesterol: phosphatidylserine liposomes; ii) HEPES buffer (pH, 7.4); iii) 5% propylene glycol; iv) 10% ethanol; v) 0.05% sodium lauryl sulfate; and vi) a suspension of the same lipids used to form the liposomes that were not processed so as to produce a bilayer configuration. Topical application of the liposomally based formulation resulted in a significantly higher accumulation of CF in the pilosebaceous units than the application of any of the other non-liposomal formulations. There was excellent correlation between the two analytical methods used to determine CF deposition into the sebaceous glands. PMID- 1607676 TI - Demonstration of skin-derived antileukoproteinase (SKALP) in urine of psoriatic patients. AB - Recently we described a new elastase inhibitor (skin-derived antileukoproteinase, SKALP) that is expressed in psoriatic epidermis and cultured keratinocytes, but is virtually absent in normal skin. In this study we investigated whether SKALP activity could be measured in urine of psoriatic patients and healthy controls. We found that urine of psoriatic patients contained considerable amounts of anti elastase activity, whereas this activity in urine from normals was significantly lower. The properties of the urinary anti-elastase activity in psoriatic patients were indistinguishable from that of epidermal SKALP. It was found to be a cationic, heat-stable protein with an apparent molecular weight of 11 kDa on sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and a K(i) of approximately 2 x 10(-11) M. In addition, in Western blotting partially purified inhibitor from urine was found to react with a polyclonal anti-SKALP serum. SKALP in urine was either present in a free form or in a latent form, most likely complexed with elastase. We speculate that SKALP in urine of psoriatic patients is derived from the epidermis, and that it might serve as a marker for disease activity. PMID- 1607677 TI - Characterization of a glucocorticosteroid-induced inhibitor of interferon-gamma induction of HLA-DR expression. AB - Interferon gamma (IFN-gamma) induces human leukocyte antigen (HLA)-DR antigen expression on a variety of cell types, and in human skin cells this induction is inhibited by trypsin inhibitors. Recently a trypsin-like protease was characterized whose activity is required for HLA-DR induction in a hybrid epidermal cell line. Glucocorticosteroids also inhibit IFN-gamma-induced HLA-DR expression, and similarities have been noted between the inhibition by trypsin inhibitors and by glucocorticosteroids. To assess the possibility that glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression might be due to induction of an inhibitor of trypsin activity that is re-expression, we examined culture medium supernates (CM) of glucocorticosteroid-treated cells for HLA-DR- and trypsin-inhibitory activities. We report here that CM of glucocorticosteroid-treated H12 cells contain inhibitors of HLA-DR expression and of trypsin activity, but that the two inhibitors are not identical. H12 cells constitutively secrete a greater than 30,000 MW, acid- and heat-stable trypsin inhibitor, whose expression is not modulated by glucocorticosteroid or IFN-gamma, and that does not inhibit IFN-gamma-induced HLA-DR expression. The HLA-DR inhibitor, on the other hand, is present only in CM of glucocorticosteroid treated cells, is distinct from glucocorticosteroid itself, of a MW less than 500 and does not inhibit trypsin. We conclude, therefore, that the glucocorticosteroid inhibition of IFN-gamma-induced HLA-DR expression is by a mechanism other than secretion of a trypsin inhibitor. PMID- 1607678 TI - Topical minoxidil in alopecia areata: no effect on the perifollicular lymphoid infiltration. AB - The therapeutic value of topical minoxidil in alopecia areata (AA) has been investigated in recent years, with variable results. Although the mechanism whereby minoxidil may stimulate hair regrowth in some cases of AA has not yet been elucidated, there have been reports of a decrease in the perifollicular infiltrates of mononuclear leukocytes (MNC)--particularly T lymphocytes--that characterize this condition, in patients "responding" to topical minoxidil. In a randomized and double-blind study, we have investigated the effect of 5% topical minoxidil versus placebo (vehicle alone) on the extent and composition of the perifollicular MNC infiltration in 20 patients having extensive AA (26-99% scalp hair loss). The proportions of hair follicles showing perifollicular infiltration by MNC and their main subsets were determined with histologic and immunohistochemical stainings of scalp biopsies obtained before treatment, after 12 weeks of randomized double-blind minoxidil versus placebo treatment, and after 12 additional weeks during which all patients received minoxidil. Six of the patients showed cosmetically acceptable hair regrowth (CAHR) at the end of the 24 weeks and this was associated with a significant decrease in the proportions of follicles infiltrated by total T and B lymphocytes, macrophages, and Langerhans cells at week 12, and by total T lymphocytes at week 24. However, no significant differences in the extent or composition of the perifollicular infiltrates were detected at week 12 between patients receiving minoxidil and placebo, or between the week-12 and week-24 biopsies of those patients who first received placebo and then minoxidil. These findings indicate that in AA the reduction in perifollicular T-cell infiltration associated with CAHR is not attributable to an effect of topical minoxidil. PMID- 1607679 TI - Cytomembrane-derived Birbeck granules transport horseradish peroxidase to the endosomal compartment in the human Langerhans cells. AB - It has been previously shown that the cytomembrane of human Langerhans cells (LC) has the capacity to fold upon itself, thereby forming Birbeck granules (BG), which then internalize. I confirmed this by exposing LC in vitro to horseradish peroxidase (HRP) at +8 degrees C and +37 degrees C. On incubation at +37 degrees C the label appeared not only in BG, but also in tubular structures and vesicles of different shapes and sizes. Interconnections between these labeled endosomal structures were common. The LC cytomembrane could form BG at +8 degrees C and, moreover, the BG was the only organelle that was labeled and internalized at this temperature. Thus, cytomembrane-derived BG are endocytotic in nature and link the exterior of the cell and the endosomal compartment. The membrane interlinking of the BG may eventually dissolve and the BG then transform into an endosomal vesicle. PMID- 1607680 TI - Ontogenesis of the basement membrane zone after grafting cultured human epithelium: a morphologic and immunoelectron microscopic study. AB - Sheets of cultured epithelial cells have been successfully used as autografts for the permanent coverage of patients with full-thickness burns and as allografts to stimulate the healing of chronic skin ulcers. The basement membrane zone (BMZ), composed of lamina lucida, lamina densa, and anchoring fibrils, plays a pivotal role in the firm adherence of the epidermis to the dermis. The present study describes the ultrastructural development during various stages of wound healing after resurfacing different wound areas by cultured epithelial grafts. For this purpose, biopsies were obtained from five patients 5 d to 4.5 years after resurfacing full-thickness burns with cultured autografts, and from five patients at various stages after treatment of excised tattoos and chronic skin ulcers with cultured allografts. One biopsy was taken from a spontaneously healed burn wound 30 years post-injury. Ultrathin sections were prepared for transmission and immunoelectron microscopy, using monoclonal antibodies against type IV and VII collagen. Findings were compared to controls of age- and site-matched normal skin. Eleven days after grafting, the first BMZ features had regenerated, including lamina lucida, a discontinuous lamina densa, hemidesmosomes, and sparse anchoring fibrils. The process of de novo synthesis of BMZ components had begun, and within 4 to 5 weeks complete reformation of BMZ was observed, including normal distribution of anchoring fibrils. Immunolabeling of type VII collagen was first observed upon the lower part of lamina densa at day 11 and steadily increased, reaching normal values 5 weeks after grafting. In contrast, gold deposition of type IV collagen upon lamina densa was strongly increased at day 19 compared to normal. This high expression reduced a little at 5 weeks, but remained high up to 30 years after injury. Long-term burn scars exhibited pseudopodia-like extensions of all basal cells, abundant anchoring fibrils, and an increased amount of arching anchoring fibrils. These features might compensate for the lack of proper rete ridges. PMID- 1607682 TI - Aberrant cytokine production by Sezary syndrome patients: cytokine secretion pattern resembles murine Th2 cells. AB - Sezary syndrome (SzS), the leukemic stage of cutaneous T-cell lymphoma (CTCL), is typically a CD4+ T-cell lympho-proliferative disease characterized by numerous immunologic abnormalities, including decreased T-cell responses to antigens and mitogens, decreased natural killer and lymphocyte-activated killer cell activities, eosinophilia, and increased levels of immunoglobulins, particularly IgE and IgA. Because this constellation of abnormalities is reminiscent of the pleiotropic in vitro activities of IL-4 and IL-5, we examined the possibility that malignant T cells in SzS may be producing increased amounts of IL-4 with a concomitant decrease in IL-2 and IFN-gamma production. Such a cytokine secretion pattern would be similar to that produced by murine Th2 cells. Serum IL-4 enzyme linked immunosorbent assay measurements revealed that 33% of SzS patients (n = 21) had levels of IL-4 significantly higher (mean, 7.2 pg/ml; range, 0-48, p less than 0.05) than normal controls (mean, 1.59; range, 0-3.1). Although the majority of tested patients had elevated serum IgE, no direct correlation between serum IL 4 levels and serum IgE levels was observed. Peripheral blood mononuclear cells (PBMC) isolated from SzS patients and stimulated with phytohemagglutinin (PHA) produced significantly higher levels of interleukin (IL)-4 and significantly lower levels of IL-2 and interferon (IFN)-gamma than did PBMC from normal controls (p less than 0.02, p less than 0.05, and p less than 0.02, respectively). PBMC from SzS patients in remission produced IL-4 and IL-2 levels similar to that of the normal controls. To determine if IFN-gamma could inhibit the increased IL-4 production by PHA-stimulated PBMC from SzS patients, IFN-gamma was added to culture at 0, 24, or 48 h prior to the addition of PHA. Significant decreases in IL-4 production were seen only in cultures incubated with IFN-gamma for 24 and 48 h prior to the addition of PHA. IL-2 levels were not affected by IFN-gamma incubation. The increased IL-4 and decreased IL-2 and IFN-gamma production by PBMC from SzS patients suggests that Sezary cells have a cytokine profile similar to murine Th2 cells. Moreover, this cytokine secretion pattern may play an integral role in the immunopathogenesis of advanced CTCL. The results also suggest that IFN-gamma be a useful component in the spectrum of therapeutic approaches to SzS. PMID- 1607681 TI - Pregnant women with endemic pemphigus foliaceus (Fogo Selvagem) give birth to disease-free babies. AB - Endemic pemphigus foliaceus (PF), also known as Fogo Selvagem (FS), is an organ specific autoimmune disease mediated by autoantibodies. These autoantibodies are disease specific, predominantly restricted to the IgG4 subclass, and pathogenic, as demonstrated by passive transfer studies. In contrast to pemphigus vulgaris, neonatal skin disease does not appear to occur in babies born to mothers with non endemic PF or FS. In the present study we have examined 19 mother/neonate pairs where the mother had documented FS. Mothers and neonates were examined soon after delivery and tested by immunofluorescent (IF) techniques for FS autoantibodies either in circulation (mothers' sera or babies' cord blood) or bound to the neonatal epidermis. All neonates included in this study were born with normal skin. Twelve biopsies from 17 neonates showed negative direct IF using both FITC antihuman IgG or monoclonal anti-IgG subclass antibodies. In five biopsies the epidermal ICS of the babies showed weak staining. In 10 of the 19 cord sera tested, FS IgG autoantibodies were undetectable; in nine, these autoantibodies were present in low titers (less than 1:40). The sera of the mothers showed higher titers of FS autoantibodies, and IgG4 was the predominant IgG subclass autoantibodies. It appears that human placenta may modulate the expression of disease in the newborn by operating as a "biologic immunoadsorbent" of pathogenic autoantibodies. PMID- 1607683 TI - Endemic human T cell lymphotropic virus type II infection among isolated Brazilian Amerindians. AB - Evidence for human T cell lymphotropic viruses (HTLV) was sought in sera and cells collected from adults in 13 isolated South and Central American Indian tribes. Serologic tests identified frequent HTLV-II-like reactivity among the Cayapo and Kraho tribes, who live 330 km apart in Central Brazil. Polymerase chain reaction analyses of viral DNA in cell pellet and plasma fractions confirmed the virus as HTLV-II. Both tribes speak Ge and, at the time of blood collection (1974), subsisted as hunter/gatherers and slash and burn agriculturalists. Further testing of plasma from Cayapo and Kraho of all ages revealed overall HTLV-II prevalence rates of 33.3% and 12.2%, respectively, with increasing prevalence associated with age and female gender. These data reveal for the first time a high prevalence of HTLV-II infection in remote South American Indians with little contact with non-Indians. Thus, HTLV-II is postulated to be an ancient human virus in the New World. PMID- 1607684 TI - Effect of cyclooxygenase inhibition on amphotericin B-induced lung injury in awake sheep. AB - Amphotericin therapy in humans has been reported to cause severe pulmonary dysfunction in some patients, and these abnormalities have been reproduced in unanesthetized sheep. To determine the role of cyclooxygenase products in this response, paired, random-order experiments in 11 sheep were done using the cyclooxygenase inhibitor ibuprofen. Ibuprofen blunted increases in pulmonary artery pressure (Ppa) after amphotericin (peak Ppa 38 +/- 3 cm H2O in amphotericin-alone group vs. 30 +/- 1 cm H2O in ibuprofen + amphotericin group, P less than .05) and reduced peak lung lymph flow to approximately 170% of baseline compared with 350% of baseline in amphotericin-alone group (P less than .05). In addition, the increase in airflow resistance across the lung and the decrease in partial pressure of oxygen seen after amphotericin was blocked by ibuprofen. Therefore, amphotericin-induced lung dysfunction is produced in part through the generation of cyclooxygenase products of arachidonic acid metabolism and can be ameliorated by pretreatment with the cyclooxygenase inhibitor ibuprofen. PMID- 1607685 TI - Safety and immunogenicity of the synthetic malaria vaccine SPf66 in a large field trial. AB - In the first field trial with synthetic malaria vaccine SPf66 in a large population naturally exposed to malaria, 9957 persons greater than 1 year old and residing on the Colombian Pacific coast received three doses of the vaccine. To evaluate vaccine safety, clinical observations were made 30 min and 48 h after each immunization. There were no adverse reactions in 95.7% of cases. In the 4.3% of cases with adverse reactions, local induration and erythema were the most frequent. In a randomly selected group of vaccinees, anti-SPf66 antibody titers were measured after the third dose: 93% of the vaccinees raised antibodies to SPf66. Among these, 55% had titers greater than 1:1600. These results demonstrate the safety and immunogenicity of the SPf66 vaccine in a large field trial. PMID- 1607686 TI - Detection of Plasmodium falciparum by polymerase chain reaction in a field study. AB - Detection of Plasmodium falciparum by polymerase chain reaction (PCR) was evaluated in 33 P. falciparum-infected patients with two different amplification systems over 5-7 days of curative treatment. In the K1-14 system, a P. falciparum DNA fragment of 206 bp was detected, and in the circumsporozoite (CS) system, a fragment of 800 bp was detected. The K1-14 and CS systems identified 95% and 93%, respectively, of 103 microscopically identified specimens; both systems detected as few as 11 parasites/microliters among these specimens. Specimens from 20 smear and history-negative controls were all negative by both PCR systems. The K1-14 and CS systems detected P. falciparum DNA in 53% and 20%, respectively, of blood films collected on the first day and 3% and 0 of the blood films collected on the fourth day after reversion to microscopic negative. The simultaneous use of two independent PCR systems to monitor patients during curative treatment of P. falciparum infections convincingly demonstrated that P. falciparum DNA was present transiently in the blood of infected patients at a time when the parasite could no longer be detected microscopically. PMID- 1607687 TI - Epidemiology of Helicobacter pylori in southern China: identification of early childhood as the critical period for acquisition. AB - A large cross-sectional study to investigate the prevalence and possible modes of transmission of Helicobacter pylori was done in southern China. Serum samples (1727) were collected from Guangzhou city and three rural areas of Guangdong Province, and the prevalence of H. pylori infection was determined using an ELISA. Each subject completed a questionnaire. The overall prevalence of H. pylori infection was 44.2%; a significantly higher prevalence was found in Guangzhou (52.4%) than in the rural areas (38.6%). This difference was generally reflected in the group 0-5 years old, but the rate of increase in seroprevalence for H. pylori over 5 years of age was similar (1%/year). This study provides important new data on the acquisition of H. pylori, particularly in the early years of life, and shows that density of living conditions is a prime determinant in the acquisition of H. pylori. PMID- 1607688 TI - Modern medicine versus an ancient scourge: progress toward control of onchocerciasis. AB - Control of human onchocerciasis has been problematic. Vector control is practical and effective in only a circumscribed region of West Africa. Even in this area, control depends on meticulous monitoring of the vector and associated parasite species and precise application of requisite larvicide on a regular basis. As an alternative to vector control, chemotherapy-based control has been revolutionized by the finding that ivermectin, a novel semisynthetic macrocyclic lactone, is acceptable for mass distribution at the community level and that it represents an effective means of disease control when given once yearly. Efforts are underway to develop a vaccine to prevent infection. PMID- 1607689 TI - Hemolytic-uremic syndrome and Vero cytotoxin-producing Escherichia coli infection in Italy. The HUS Italian Study Group. AB - In a 3-year prospective study, 49 Italian children with the hemolytic-uremic syndrome (HUS) were examined for evidence of infection with Vero cytotoxin producing Escherichia coli (VTEC). Diagnosis of infection was established in 37 patients (75.5%) by the combined use of stool examination for VTEC and for free fecal neutralizable Vero cytotoxin and serum analysis for antibodies to the Vero toxins and the lipopolysaccharides (LPS) of three major VTEC serogroups (O157, O26, O111). Anti-LPS antibodies were detected in sera from 30 patients: 25 had antibody to O157 LPS, 4 to O26, and 1 to O111. In as many as 27 patients (55.1%), diagnosis of infection relied only on serologic findings, and the presence of antibody to LPS was the sole evidence of VTEC infection in 20 patients (40.8%). The use of LPS from different E. coli serogroups provided evidence that in Italy O157 strains are the most prevalent VTEC involved in HUS. PMID- 1607690 TI - Age-specific prevalence of serum antibodies to the invasion plasmid and lipopolysaccharide antigens of Shigella species in Chilean and North American populations. AB - Shigella species have virulence plasmids that encode outer membrane proteins (invasion plasmid antigens, Ipa) associated with pathogenicity. Western blots were used to detect antibodies to Ipa in sera from 390 Chilean children, and these responses were compared with those of a US population of infants and adults. Antibodies to lipopolysaccharide (LPS) of Plesiomonas shigelloides and Shigella flexneri 2a were measured by ELISA. Among the Chileans, there was an age related acquisition of Ipa antibodies, with 28% of 1-year-olds and 100% of children greater than or equal to 10 years showing positive responses. In contrast, none of the US infants and only 38% of the adults had antibodies to Ipa. Levels of LPS antibodies were also found to increase in an age-related manner among the Chileans. These results corroborate findings of previous epidemiologic studies which show that Shigella infections are endemic in Chile, as in other developing countries. The measurement of Ipa and LPS antibodies is a useful seroepidemiologic tool for investigating previous exposure to Shigella species in populations. PMID- 1607691 TI - Oral erythromycin prophylaxis against Streptococcus pyogenes infection in penicillin-allergic military recruits: a randomized clinical trial. AB - Historically, military recruits have required benzathine penicillin G to prevent epidemics of Streptococcus pyogenes. In this randomized clinical trial, low-dose oral erythromycin was evaluated as an alternative for prophylaxis against group A beta-hemolytic streptococci in penicillin-allergic recruits. US Marine Corps recruits (186) reporting penicillin allergy were randomly given either oral erythromycin (250 mg twice a day) or a vitamin (one tablet daily) for 60 days. Evidence of infection was defined as a two-dilution rise in anti-streptolysin O titer. The erythromycin group had a significantly lower risk of S. pyogenes infection than did the vitamin group (relative risk 0.44; 95% confidence interval, 0.22-0.89). There was no significant difference among the treatment groups in isolation of group A beta-hemolytic streptococci from throat cultures. Low-dose oral erythromycin appears as effective as benzanthine penicillin G in preventing S. pyogenes infection. PMID- 1607692 TI - Role of tolerance in cloxacillin prophylaxis of experimental Staphylococcus aureus endocarditis. AB - The role of tolerance was investigated in the prophylaxis of Staphylococcus aureus endocarditis with cloxacillin in rats. The effect of a single dose of 500 mg/kg, two 80 mg/kg doses 3 h apart, and a single dose of 80 mg/kg, alone or in combination with a single dose of 4 mg of gentamicin/kg, were compared for a tolerant strain of S. aureus and its isogenic nontolerant variant. At all dosages, cloxacillin was significantly less effective in preventing endocarditis with the tolerant strain than with the nontolerant variant. With the high dose of cloxacillin or two successive lower doses, nearly complete protection could be obtained against the nontolerant strain. However, for the tolerant strain, only the combination of cloxacillin and gentamicin afforded almost complete protection. For the tolerant strain, no serum bactericidal activity was found at the time of bacterial challenge after an injection of any dose of cloxacillin. These results suggest that the in vitro phenomenon of tolerance may have relevance in vivo. PMID- 1607693 TI - Type b capsule inhibits ingestion of Haemophilus influenzae by murine macrophages: studies with isogenic encapsulated and unencapsulated strains. AB - Phagocytosis may be important in clearing Haemophilus influenzae from the bloodstream. To define the effect of type b capsule on phagocytosis, binding and ingestion by macrophages was measured for 5 isogenic sets of capsule-sufficient strains (clinical isolates and type b transformants of capsule-deficient mutants) and capsule-deficient mutants (strains lacking a 9-kb EcoRI fragment of chromosomal DNA associated with type b capsule expression). Capsule-sufficient strains were not bound in the absence of serum, whereas capsule-deficient strains were bound and ingested (1.8-5.1 organisms/macrophage; 59%-97% ingested). In the presence of nonimmune serum, capsule-sufficient strains were largely bound but not ingested (4.7-7.2 organisms/macrophage; 7%-21% ingested), whereas capsule deficient strains were nearly all ingested (6.2-10.5 organisms/macrophage; 93% 97% ingested). Strains resisting ingestion caused persistent bacteremia 24 h after intravenous challenge in mice and were more likely than readily ingested strains to cause persistent bacteremia or death in infant rats. Thus, type b capsule inhibits ingestion by macrophages; resistance to ingestion may be an important virulence determinant of type b organisms. PMID- 1607694 TI - Secreted antigens of Mycobacterium tuberculosis: characterization with T lymphocytes from patients and contacts after two-dimensional separation. AB - Little is known about T cell antigens involved in immunity against Mycobacterium tuberculosis. Most model systems use in vitro culture of human T lymphocytes with bacterial lysates or secreted proteins as antigens. In this study, proteins from 3-week-old M. tuberculosis culture filtrates were separated by two-dimensional PAGE and subsequently transferred into soluble phase. The resulting 480 fractions were screened with T lymphocytes from tuberculosis patients and healthy contacts. T cells from all 9 patients and from 8 of 10 tuberculin-positive contacts preferentially responded to a cluster of acidic proteins (pI 4-5) with molecular masses of 30-100 kDa, although they also recognized a number of other fractions. In contrast, of 7 tuberculin-negative contacts, 4 were not and 3 were only weakly stimulated by this cluster region. Therefore, this distinct cluster of secreted proteins seems to comprise dominant T cell antigens of M. tuberculosis. PMID- 1607695 TI - Use of DNA probes to detect Mycobacterium intracellulare and "X" mycobacteria among clinical isolates of Mycobacterium avium complex. AB - A mycobacterial DNA probe (designated X) was recently developed to help identify Mycobacterium avium complex (MAC) isolates that are nonreactive with probes specific for M. avium or Mycobacterium intracellulare. The prevalence of X probe positive mycobacteria in clinical specimens and their role in causing disease is unknown. Using a DNA probe kit that includes the X probe, we characterized 100 consecutive clinical MAC isolates as M. avium, M. intracellulare, or X. Lysates from 81 of the isolates reacted with the M. avium probe, 13 with the M. intracellulare probe, 3 with the X probe, and 3 failed to hybridize with any of the probes. All three X-positive isolates were recovered from sputa of patients who were recent immigrants to the United States and who presented with hemoptysis. One isolate was from a Hispanic man infected with human immunodeficiency virus type 1 (HIV-1) and the other 2 were from Filipino patients with no HIV-1 risk factors. This study also showed a higher than expected number of M. intracellulare isolates from blood and cerebrospinal fluid of HIV-1 infected patients. PMID- 1607696 TI - Tuberculin skin test reactivity among adults infected with human immunodeficiency virus. AB - Infection with the human immunodeficiency virus type 1 (HIV-1) results in decreased cell-mediated immunity, which includes decreased delayed hypersensitivity to skin test antigens. HIV-1 seropositivity and skin test reactivity to purified protein derivative (PPD) were determined among 2042 healthy Haitian adults with normal chest radiographs. Among HIV-1-seropositive individuals, 52.3% (146/279) had PPD reactions greater than or equal to 10 mm compared with 67.2% (1184/1763) of the seronegative adults (P less than .001). However, the percentage of HIV-1-seropositive individuals with PPD reactions greater than or equal to 5 mm was similar to the percentage of seronegative adults with PPD reactions greater than or equal to 10 mm (180/279 [64.5%] vs. 1184/1763 [67.2%]). Assuming that the rate of prior infection with Mycobacterium tuberculosis was similar for HIV-1-seronegative and -seropositive populations, these data provide support for the recent recommendations to use induration of greater than or equal to 5 mm as evidence of past infection with M. tuberculosis in HIV-1 seropositive adults. PMID- 1607697 TI - In vitro inhibition of a variety of human immunodeficiency virus isolates by a broadly reactive, V3-directed heteroconjugate antibody. AB - The cytotoxic efficacy of a heteroconjugate antibody composed of OKT3 cross linked to a broadly reactive antibody directed against the GPGRAF sequence of the gp120 V3 region has been characterized. The heteroconjugate antibody could completely inhibit viral replication of both the IIIB and MN isolates of human immunodeficiency virus (HIV) at concentrations as low as 0.5 ng/ml. At an antibody concentration of 1 micrograms/ml, heteroconjugate-mediated cytotoxicity occurred at effector-to-target ratios as low as 0.006:1. Eight different HIV isolates were tested for in vitro inhibition by the anti-V3-OKT3 conjugate, and all but one were completely inhibited for at least 7 days. These results indicate that heteroconjugate antibodies are a potent, effective means by which HIV infected cells can be killed and viral replication suppressed. PMID- 1607698 TI - The treatment of cholera: clinical science at the bedside. AB - In 1959-1961, two major international centers for the study of cholera were established in Calcutta and in Dacca, Bangladesh. As the result of collaborative work in these centers, a simple effective oral therapy for cholera, using ingredients available in virtually every part of the world, was defined. Through the well-coordinated efforts of the World Health Organization (WHO), knowledge of how to prepare and administer oral rehydration therapy has now been disseminated throughout most of the world. With this background, when Peru was attacked in 1991 by a massive and totally unanticipated outbreak of cholera, a remarkably well-organized national response to the epidemic achieved a survival rate greater than 99% in greater than 300,000 cholera patients during the first year of the epidemic. Thus the results of clinical research on the Indian subcontinent, widely disseminated through educational programs by the WHO, have resulted in unparalleled success in the treatment of the largest epidemic outbreak of cholera in the 20th century. PMID- 1607699 TI - Persistence of measles antibody after revaccination. AB - To evaluate persistence of measles antibody after revaccination, antibody levels were measured 6 years after revaccination of 40 hemagglutination-inhibition (HAI) antibody-negative students who had participated in a serosurvey in Massachusetts. Twelve subjects who had been HAI antibody-positive and were not revaccinated were included as a comparison group. Before revaccination, 7 revaccinees had no detectable plaque reduction neutralization (PRN) antibody (group 1) and 33 had low levels of PRN antibody (group 2). Three weeks after revaccination, all in group 1 and 30 (90%) of 33 in group 2 had developed a fourfold or greater rise in PRN antibody. Six years after revaccination, all subjects had PRN-detectable antibody. However, 12 in group 2 (36%) had antibody titers less than or equal to 1:120 compared with none in group 1 (P less than .01). Persons without PRN antibody will respond to revaccination and maintain protective antibody titers. In contrast, persons with low levels of PRN antibody may respond initially to revaccination, but their antibody titers may fall again to low levels. PMID- 1607700 TI - Infection by an indole-negative variant of Vibrio vulnificus transmitted by eels. PMID- 1607701 TI - Impairment of immunogenicity of Salmonella typhi Ty21a due to preexisting cross reacting intestinal antibodies. PMID- 1607702 TI - Absence of human T cell lymphotrophic virus (HTLV) type I and II DNA in French anti-HTLV-I/II-negative intravenous drug users. PMID- 1607703 TI - Ketoconazole in the treatment of antimony- and pentamidine-resistant kala-azar. PMID- 1607704 TI - Genotypic and phenotypic methods for the investigation of a nosocomial Legionella pneumophila outbreak and efficacy of control measures. AB - To determine the source of a nosocomial outbreak of Legionella pneumophila serogroup 1 infection and the efficacy of control measures, clinical and environmental isolates were characterized by molecular subtyping and disease surveillance was conducted. The outbreak involved 32 cases (relative risk, 4.0; P less than .001 vs. previous period). Water colonization with L. pneumophila serogroup 1 and patients' exposure to faucet use incriminated the water system as the environmental source. Monoclonal antibody typing showed that patient isolates belonged mainly to type Pontiac and water isolates mainly to type Bellingham (P less than .001). By four genotypic techniques, outbreak-related isolates from patients and the water system were found to be clonally related and distinct from control strains (P less than .001). Heat and UV light treatment of the water system showed a protective efficacy of 88% (95% confidence interval, 75%-94%). These findings indicate that phenotypic variation may interfere with monoclonal antibody typing of legionellae and that waterborne legionellosis can be controlled by physical disinfection. PMID- 1607705 TI - Aspects of pathogenesis of serious group A streptococcal infections in Sweden, 1988-1989. AB - Serotypes of serious, sometimes fatal, streptococcal infections in Sweden during 1988-1989 were analyzed. The T1M1 type totally dominated, representing almost 70% of all group A streptococci from serious and uncomplicated infections at the peak of the outbreak. Immunoblots of isolates from various patient groups showed that all isolates produced high amounts of erythrogenic toxin (ET) B and high amounts of ET-C, whereas ET-A was released only in small amounts and from few isolates. ELISAs showed high antibody levels to these toxins and to the M1 antigen in patients with uncomplicated infections. Low antibody levels against M1 were seen in patients with bacteremia and in fatal cases; the latter also had low antibody levels against ET-B. It seems likely that a combination of production of large amounts of toxin and low antibody titers to it and to the M antigen of the infecting isolate are determining factors for the outcome of the infection. No signs of primary immune deficiency were noted. PMID- 1607706 TI - IgG antibody reactive with five serotypes of Streptococcus pneumoniae in commercial intravenous immunoglobulin preparations. AB - Intravenous immunoglobulin replacement is recommended for immunoglobulin deficiency, but comparison of the efficacy of intravenous immunoglobulin preparations (IVIGs) has been hindered by the lack of standardized assays to measure immunoglobulin levels against important bacterial pathogens. IgG reactive with five commonly isolated serotypes of Streptococcus pneumoniae in four commercially available IVIGs was measured by ELISA. Specific antibody to capsular polysaccharide was quantitated before and after adsorption with cell wall polysaccharide (CWPS). All IVIGs contained measurable levels of antibody to the five pneumococcal serotypes, although the levels against an individual serotype varied by as much as sevenfold from one preparation to another. Each IVIG also contained substantial concentrations of IgG reactive with CWPS. The amount of each IVIG that protected mice was nearly identical after the doses were adjusted on the basis of specific IgG measured by ELISA, thereby providing proof in vivo of the validity of this in vitro assay system. PMID- 1607707 TI - Growth of Haemophilus influenzae in human milk: synthesis, distribution, and activity of IgA protease as determined by study of iga+ and mutant iga- cells. AB - The nonencapsulated, IgA protease-positive Haemophilus influenzae strain Rd and serogroup b clinical isolates were found to proliferate in human milk. Growth did not require supplemental X and V factors. In milk, strain Rd synthesized IgA protease, but it was completely inhibited by antibody, so secretory IgA in milk cultures remained intact. Inhibition was largely attributable to IgA1 antibodies. Rd cells also aggregated during growth in milk and showed colony size variation, whereas a protease-negative mutant of Rd (Rd225DK) aggregated less and had uniform colony size. Like differences in protease inhibition, these differences in growth pattern were mediated by secretory IgA1. Thus, milk antibody not only inhibited the extracellular protease but also interacted directly with the enzyme precursor or related antigens on growing bacterial cells. This self-protective property of milk secretory IgA may be an important immunologic attribute for the upper respiratory mucosa of the infant. PMID- 1607708 TI - Complement factor 9 deficiency in serum of human neonates. AB - The serum concentration of complement factor C9 (C9) was 260 +/- 47 micrograms/ml (+/- SE) in 14 mothers and less than 42 micrograms/ml in each of their 14 neonates. During incubation for 60 min, 11 of 14 maternal sera and 3 of 14 neonatal sera reduced the survival of Escherichia coli O7w:K1:NM to less than 20% of the original inoculum (P less than .03). Eleven neonatal sera did not kill the bacteria. Supplemental C9 (60 micrograms/ml) enhanced the bactericidal capacity of 10 neonatal sera. 125I-labeled C9 was deposited onto E. coli by neonatal sera, but less efficiently than by pooled adult sera. Supplemental IgG enhanced 125I labeled C9 deposition and potentiated the bactericidal activity of exogenous C9. Therefore, neonatal sera contained diminished concentrations of C9 and killed E. coli inefficiently. In neonatal sera, supplemental C9 was deposited onto E. coli and enhanced bactericidal activity. These effects of C9 were potentiated by supplemental IgG. PMID- 1607709 TI - Contribution of tumor necrosis factor to host defense against staphylococci in a guinea pig model of foreign body infections. AB - The contribution of the cytokine tumor necrosis factor (cachectin; TNF) to host defenses against staphylococcal foreign body infections was studied in vivo. In tissue cages subcutaneously implanted into guinea pigs, progressive infection was initiated by a very low inoculum (100 cfu) of Staphylococcus aureus with a success rate of 100%, as is frequently encountered in related clinical situations. Locally injected autologous bacterial components derived from the cell wall of S. aureus, in particular peptidoglycan, were very active in raising TNF levels in tissue cage fluid and in preventing the development of infection by the 100% infective dose of the test strain. Furthermore, injection of murine recombinant TNF into tissue cages could substitute for the bacterial components in preventing experimental infection by S. aureus. The protective effect of TNF eliciting bacterial components could be neutralized by anti-TNF antibodies. A local increase in TNF levels might improve host defenses against staphylococcal foreign body infections. PMID- 1607710 TI - Survival for women and men with AIDS. AB - To compare trends in the length of survival for women and men after diagnosis of AIDS, data were analyzed for 139 women and 7045 men who were reported with AIDS in San Francisco between July 1981 and 31 December 1990. Patients were followed prospectively through 15 May 1991. The median survival for women (11.1 months) was significantly shorter than that for men (14.6 months). When data were stratified by year of diagnosis, significantly improved survival was observed in recent years for both women and men, although survival for women remained significantly shorter than that for men. Among those who received either zidovudine or 2',3'-dideoxyinosine, survival did not differ by gender. However, among those not receiving therapy, survival was significantly shorter for women. These results suggest that the shorter survival of women may be a result of factors other than gender, possibly including less use of antiretroviral therapy. PMID- 1607711 TI - Human immunodeficiency virus type 1 infection in women attending a sexually transmitted diseases clinic in Kenya. AB - A cross-sectional study was conducted among women attending a sexually transmitted diseases clinic in Nairobi, kenya, to determine the prevalence of and associated risk factors for human immunodeficiency virus (HIV) type 1 infection. HIV-1 antibody was detected in 13.8% of 600 women. This virus was found most frequently in prostitutes (odds ratio [OR], 7.2), in women reporting a history of genital ulcers (OR, 2.3), and in those with a current diagnosis of genital ulcers (OR, 5.1). Lifetime duration of oral contraceptive use was significantly greater in HIV-1-positive women. Multivariate analysis revealed an association between genital ulcers and HIV-1 infection (OR, 3.8). The strongest association for HIV-1 infection, however, occurred with genital ulcers in combination with the use of oral contraceptives (OR, 25.7). PMID- 1607712 TI - The pathogenesis of leprosy in the nine-banded armadillo and the significance of IgM antibodies to PGL-1. AB - Twenty-seven nine-banded armadillos captured from the wild and tested free of wild M. leprae infection were distributed into four groups. They were injected at the right hind footpad with saline suspensions of M. Leprae at doses of 10(3), 10(4), 10(5) and 10(6). PGL-1 antibody levels were estimated using an ELISA test, twice during six months before the infection and every two months after the infection. One animal from each group was sacrificed at 6, 12, 18, 24, and 30 month intervals and another eight at unspecified intervals. A thorough autopsy and histopathological examination were conducted on all of them. Of the 27 animals, 18 developed the infection. In 10, there were granulomas at the site of inoculation and in 17 the regional lymph nodes were infected. The disease spread extensively to other lymph nodes and to the liver and spleen and then to the other organs. Peripheral nerves were invaded by M. leprae in only five animals. PGL-1 antibody levels registered a positive reading in only six of the 18 animals with the infection. In armadillo leprosy, the lesions did not persist at the site of entry in all animals M. leprae multiplied in the macrophages at the site of inoculation and the reticuloendothelial cells of the lymph nodes before they spread to other organs. There was evidence of invasion of endothelial cells of capillaries and possible bacteraemia even at an early phase of the infection. Peripheral nerves were not the preferred sites of entry or multiplication of M. leprae. Progressive increase in PGL-1 antibodies was recorded in five lepromatous armadillos with disseminated infection and high bacterial load. However, PGL-1 antibodies response was not sensitive enough to detect early disease. PMID- 1607713 TI - Paucibacillary multidrug therapy in leprosy. 7 1/2 years experience. AB - Three hundred and twenty-three paucibacillary (PB) leprosy patients were treated with WHO-recommended multidrug therapy (MDT) and followed up for over 7 1/2 years. The paucibacillary MDT regimen (PBR) was well accepted and tolerated. Complete clinical regression was attained in 61.2% patients after 6 doses of PBR. Persistence of clinical activity after 6 months of therapy was associated with occurrence of type I upgrading reaction, presence of six or more patches and more than two thickened major nerve trunks. Reversal reactions were encountered in 15.9% patients, one third of which were accompanied by severe neuritis. Delayed upgrading reaction occurred in six patients, two patients had relapse one and two years after stopping of PBR. The WHO recommended MDT regimen for paucibacillary cases needs careful evaluation and it may be necessary to extend the treatment beyond six months in certain situations. PMID- 1607714 TI - Indeterminate leprosy: a therapeutic evaluation. AB - Out of 50 cases of indeterminate leprosy, 46 were male and 4 were female. The only clinical finding was a single hypopigmented macule in 38 (76%) cases. Nine (18%) patients had two and three (6%) cases had three hypopigmented macules. All patients were treated with multidrug therapy for one year. At the end of six months, the lesions were still active in 12 (24%) cases. At the end of one year of treatment it was found that 33 (66%) patients became inactive and 3 (6%) cases were still to be active. The study shows that all indeterminate leprosy cases must be treated with multidrug therapy till all signs of activity are subsided. PMID- 1607715 TI - Study of the characteristics and causes of relapse amongst leprosy cases in an urban area (Calcutta). AB - In this retrospective study of the 3737 cases of leprosy released from treatment and followed-up during 1975 to 1990, 63 had relapsed giving an overall relapse rate of 1.69%. The relapse rate was significantly higher in the immunologically unstable N?L (Borderline) cases (2.9%). It was also higher in those who had dapsone monotherapy (1.92%) compared to those who had multidrug therapy (1.01%). The relapse rate was higher in the 10 to 29 years age group and among those who became pregnant suggesting puberty and pregnancy could be risk factors. Males had a significantly higher relapse rate (2.1%) than females (1.1%). 45.2% of relapses in N (Non-lepromatous) cases occurred within 24 months and 71.4% within 36 months of stopping treatment. In those having monotherapy, 57.1% of relapses occurred within 24 months and 76.8% within 36 months. Regularity in treatment did not seem to have much influence on relapse rates. PMID- 1607716 TI - BI of patient vs BI of individual sites. AB - An analysis of 200 skin smear results from multibacillary patients showed that the average bacteriological index (BI) of a patient varied considerably from his site-wise highest BI. The average BI was equal to site wise highest BI only in 17.5% of cases and in the rest, it ranged from 99% to as low as 36% of the highest site-wise BI. In follow-up smears, site-wise consistency of the highest BI was found in 96% of cases. It is suggested that for follow-up purposes, repeating smear from only one such site would be adequate. PMID- 1607717 TI - Hyperkeratotic and verrucous skin lesions on lower extremities of leprosy patients. AB - Three morphological varieties of hyperkeratotic and verrucous skin lesions on the anterior aspect of ankle joints in patients with leprosy are described: (i) verrucous lesions with thread-like horny projections similar to filiform warts; (ii) irregular compact hyperkeratotic lesions with deep fissures in between; and (iii) hyperkeratotic lesions with linear fissures corresponding to the transverse creases on the anterior aspect of the ankle. Chemical cautery was useful for the treatment of the first two varieties, and a potent topical corticosteroid with salicylic acid was useful for the third. PMID- 1607718 TI - Hypopigmented macules in leprosy--a histopathological and histochemical study of melanocytes. AB - Study of the number of melanocytes and amount of pigmentation in hypopigmented lesions and adjacent normal areas in 20 leprosy patients showed no differences in these parameters. It appears that hypopigmentation in leprosy lesions could be caused by defective transfer of melanin into keratinocytes. PMID- 1607719 TI - Palmar involvement in histoid leprosy. PMID- 1607720 TI - Psoriasis developing in a patch of leprosy as a Koebner phenomenon. PMID- 1607721 TI - Hereditary sensory neuropathy type-I simulating pure neuritic leprosy. PMID- 1607722 TI - Acquired digital fibrokeratoma in a patient with leprosy. PMID- 1607723 TI - Tension equalizer for claw-hand correction. PMID- 1607724 TI - Leprosy in Bikaner (Rajasthan) PMID- 1607725 TI - An experiment in integration of rehabilitation of leprosy patients at Bombay. PMID- 1607726 TI - Leprosy control yesterday, today and tomorrow. PMID- 1607727 TI - Abstracts of papers presented at the XVII biennial conference of Indian Association of Leprologists, 1992. PMID- 1607728 TI - HPLC and FPLC. Recent progress in the use of automated chromatography systems for resolution of pancreatic secretory proteins. AB - Automated chromatography techniques such as high-performance (high-pressure) liquid chromatography (HPLC) or fast protein liquid chromatography (FPLC) represent a promising, new approach toward resolving the complex protein mixture of pancreatic juice. To achieve highly reproducible and rapid resolution of pancreatic protein profiles, reversed-phase, hydrophobic interaction, and ion exchange techniques are employed. Until now, none of the respectively reported methods has provided a convenient, specific procedure for diagnostic purposes. However, experimental data prove that these methods are very sensitive and furthermore, easy to handle. Therefore, it seems possible to utilize such methods for diagnostics in future. PMID- 1607729 TI - Endocrine response to intragastric and intravenous glucose challenge in the denervated dog pancreas. AB - The functional connection between the gut and the islet cells comprises nerves and gastrointestinal hormones. In this study, we quantified the incretin effect and the glucose tolerance (KG value) before and after denervation of the pancreas in dogs in order to find out whether the incretin effect is mediated by nerves. The participation of nerves was estimated by comparing metabolic tests before and after total extrinsic pancreatic denervation in 10 dogs. Fifty-nine percent of the insulin response after intragastric glucose was calculated preoperatively to be the result of incretin factors, a value similar to the 62% found in the postoperative series (with denervated pancreas). The response of GIP to intragastric glucose was not significantly different between pre- and postoperative tests. The KG values pre- and postoperative were in the same range. From our data, we conclude that extrinsic nerves of the pancreas do not seem to play an important role in mediating glucose homeostasis in dogs. PMID- 1607730 TI - Inhibitory effects of the cholecystokinin antagonist loxiglumide on pancreatic exocrine secretion and pancreatic growth in conscious rats. AB - The effects of cholecystokinin (CCK) receptor antagonist Loxiglumide (CR 1505) on pancreatic exocrine secretion and growth stimulated by chronic bile-pancreatic juice diversion to the ileum were studied in conscious rats. Pancreatic secretion was measured each day at 0900 h for 7 d. Pancreatic flow and protein output were significantly increased 24 h after bile-pancreatic juice diversion. Protein output increased each successive day, reaching maximal values of 3.6-fold above basal by the 6th and 7th d of chronic bile-pancreatic juice diversion. Fluid output reached maximal values of approx. 3.5-fold above basal by the 3rd d of chronic bile-pancreatic juice diversion. Plasma CCK increased threefold above basal levels after 24 h of bile-pancreatic juice diversion and remained three- to fourfold above basal. Intragastric bolus infusion of CR 1505 (50 mg/kg) on the 7th d of chronic bile-pancreatic juice diversion inhibited pancreatic protein and fluid secretion by 80 and 75%, respectively, 60 min after administration and by 52 and 71%, respectively, 5 h later. Pancreatic wet wt after 7 d of chronic bile pancreatic juice diversion was significantly increased by 56%, and this was completely suppressed by 50 mg/kg of CR 1505 given intragastrically every 12 h. These rests indicate that the rat with chronic bile-pancreatic juice diversion is a useful model to examine both potency and duration of the action of CCK receptor antagonists and show that CR 1505 inhibits pancreatic exocrine secretion and growth induced by endogenous CCK. PMID- 1607731 TI - Dissociation of CCK-8-induced fluid secretion from protein secretion by ion transport blockers in rat pancreas. AB - The effects of ion-transport blockers on CCK-8-induced protein output and concomitant fluid secretion were compared in isolated, perfused normal and hypertrophied rat pancreata. In the normal pancreas, perfusion with ouabain (1 mM), amiloride (1 mM), furosemide (1 mM), or SITS (0.1 mM) caused corresponding inhibition of both fluid and protein secretion that was induced by 100 pM CCK-8. Hypertrophy of the pancreas was produced by oral administration of a synthetic protease inhibitor (FOY-305) once a day for 3 wk. In the hypertrophied pancreas, perfusion with ouabain (0.1 or 1 mM) or amiloride (0.1 mM or 1 mM) decreased CCK 8-induced fluid secretion without changing CCK-8-induced protein output. Perfusion with furosemide (1 mM) inhibited both fluid and protein secretion induced by CCK-8, but the amount of inhibition of fluid secretion was much greater than that of protein secretion. Perfusion with SITS (0.1 mM) significantly decreased CCK-8-induced fluid secretion but not protein secretion. These results indicate that in contrast to a normal rat pancreas, the coupling of fluid and protein secretion induced by CCK-8 can be disrupted by experimental procedures that induce hypertrophy in the rat pancreas. PMID- 1607732 TI - Some considerations on the biology of pancreatic serous cystadenoma. AB - Five cases of pancreatic serous cystadenoma were examined pathologically, and their nuclear DNA ploidy patterns were determined. Four were unifocal tumors, and one was a multifocal tumor. The four unifocal tumors were typical serous cystadenomas. However, the multifocal tumor exhibited an increased N/C ratio, irregular nuclear margins, various-sized nuclei, coarse nuclear chromatin, and neural invasion. All tumor cells were stained with antiCA19-9 but none with antiCEA. In the antiCA19-9 staining, the four unifocal tumors and the tumors of the pancreatic tail in the multifocal case were positive only on the apical membrane, whereas the tumor cells of the pancreatic head in the multifocal case were positive within the whole cytosol. The unifocal tumors were diploid with a DNA Index (DI) of 1.0 and proliferation indices (PI) from 4.9 to 20.9% with a mean of 14.4%. In the multifocal case, the tumor in the pancreatic head was aneuploid (DI = 1.9) and had a PI of 27.8%. The multifocal sites in the pancreatic body were aneuploid (DI = 1.9) with a PI of 22.4%. We suggest that the biological property of serous cystadenoma should be revisited. PMID- 1607733 TI - Hyperthermia combined with chemotherapy and irradiation for patients with carcinoma of the oesophagus--a prospective randomized trial. AB - From 1988 to 1990, 53 patients with squamous cell carcinoma of the thoracic oesophagus underwent subtotal oesophagectomy after either preoperative hyperthermo-chemoradiotherapy (HCR therapy) or chemoradiotherapy without hyperthermia (CR therapy), in a prospective randomized trial carried out to examine the effects of hyperthermia given preoperatively. The two groups (27 patients given HCR therapy and 26 given CR therapy) were found to be comparable with regard to prognostic factors of age, site of carcinoma, TNM stage, etc. Following preoperative evaluation by an upper GI series and endoscopy, a subtotal oesophagectomy was done for all 53 patients. All the resected specimens, including the lymph nodes, were histopathologically examined, and the effects of preoperative treatment were evaluated by findings in the upper GI series and endoscopy, as well as based on the histopathology of the excised tissues. There were no viable cancer cells in the resected specimens of seven patients in the HCR therapy group (26.9%) and of two patients in the CR therapy group (7.7%). In addition, no hyperthermia complications were observed. The study suggests that preoperative HCR therapy may be a more beneficial therapy than preoperative CR therapy in patients with squamous cell carcinoma of the oesophagus who undergo a subtotal oesophagectomy. PMID- 1607734 TI - Chemotherapy resistant sarcoma treated with whole body hyperthermia (WBH) combined with 1-3-bis(2-chloroethyl)-1-nitrosourea (BCNU). AB - Seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with 1-3-Bis(2 chloroethyl)-1-nitrosourea (BCNU). All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Two patients (12%) experienced partial responses (PR). In addition, four objective tumour responses (OR) lasting more than 4 months were documented. One patient with previously rapidly growing chondrosarcoma pulmonary metastases experienced stable disease (SD) for 38 months from the onset of treatment. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. Cumulative thrombocytopenia was a therapy-limiting toxicity of the combined treatment, and occurred in six of seven patients. Acute toxicities attributable to WBH alone included transient thrombocytopenia in all patients, non-cardiogenic pulmonary oedema in two patients, and mild hypotension in five patients. Acute granulocytosis was observed in all patients. No treatment related deaths occurred. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases. PMID- 1607735 TI - Changes in mood state following whole-body hyperthermia. AB - Mood states of cancer patients were assessed pre- and post-41.8 degrees C whole body hyperthermia using the Profile of Mood States questionnaire. Results demonstrated a statistically significant increase in fatigue associated with decreased vigour which returned to baseline values by 72 h. In contrast, a significant improvement in depression was evident through 72 h following treatment. The relationship of this result to earlier studies of WBH-induced beta endorphin is discussed. PMID- 1607737 TI - Effects of local hyperthermia on the tissue levels and toxicity of three radiosensitizers in mice. AB - The toxicity of the radiosensitizers misonidazole (MISO), demethylmisonidazole (DEMISO) and pimonidazole (PIM) in mice can be affected differently when combined with local hyperthermia at 43 degrees C for 30 min. At a dose of 1 mg/g, only MISO plus heat resulted in 50% lethality in animals over a period of 7 days post treatment, whereas 100% survival was observed in the case of DEMISO and PIM. The enhanced lethality may be associated with the production of toxic intermediates of MISO. Heat did not affect the levels of DEMISO in the tissues studied (plasma, brain and tumour), whereas those of PIM were markedly lowered in tumour but not affected in brain for up to 4 h after combined treatment. MISO was found to be decreased in the tumour at all times but affected differently in brain after 1 and 2 h, initially decreasing and then increasing significantly. In all cases the treatment sequence, i.e. sensitizer plus heat or vice-versa, did not affect the rate of survival. At a dose of 2 mg/g, DEMISO plus heat was found to be more toxic when DEMISO was given first (25% survival) compared to 58% on reversal. However, the levels of DEMISO in the tissues were not affected by heat. Thus, it would appear that there is no correlation between parent drug levels measured in plasma, tumour or brain and hyperthermia-induced drug lethality. PMID- 1607736 TI - Response of canine soft tissue sarcomas to radiation or radiation plus hyperthermia: a randomized phase II study. AB - Sixty-four dogs with spontaneous soft tissue sarcomas without evidence of metastases were stratified by tumour volume and randomized to receive graded doses of radiotherapy (XRT) alone or radiotherapy plus hyperthermia (HT). An improvement in duration of local control was achieved with the addition of hyperthermia as compared with XRT alone (Wilcoxon, p = 0.040; log rank, p = 0.064). Overall frequency of late complications was not different for the two treatment arms when comparing across equivalent XRT dose groups. Frequency of distant metastases after therapy completion was not significantly different for the two treatment arms at 1 year (7.4% for XRT versus 20% for HT plus XRT) or 2 years (11.5% for XRT versus 25% for HT plus XRT) post therapy. These results suggest that a therapeutic gain was achieved for this group of tumour-bearing animals. Uni- and multivariate analyses were performed to examine the potential for various factors to influence treatment outcome. Patient related variables included tumour stage, histologic subtype and grade and tumour site. Treatment related variables included total radiation dose and 15 descriptors of temperature distributions achieved during hyperthermia. When considering patient related factors, tumour histology, grade and location were important predictors of time to minimum volume, but only tumour location influenced time to tumour regrowth. When considering treatment related factors, radiation dose was not significantly correlated with time to minimum volume or time to local regrowth, but it was correlated with probability for late normal tissue damage in the XRT alone group (p = 0.005). For the hyperthermia treatments, 13 of 15 tumour temperature distribution descriptors were correlated with time to minimum volume, but none were correlated with time to local regrowth. These results suggest that caution should be used in interpreting the value of temperature distribution descriptors in predicting for long-term local control after hyperthermia and radiotherapy, based on analysis of short-term responses. PMID- 1607738 TI - Development of thermotolerance in hsp70 induction-defective mutant of NRK cells. AB - We investigated the relation between the synthesis of inducible form of heat shock protein 70 (hsp70) and the development of thermotolerance using NRK (normal rat kidney) cells and their mutant cell line (39-1 cells). In NRK cells, hsp70 was clearly induced by conditioning treatments (42 degrees C for 2 h, 45 degrees C for 15 min or 100 microM sodium arsenite for 1 h). On the other hand, the induction of hsp70 in 39-1 cells was very low or not detectable by these treatments. Other high molecular weight hsps, hsc70 (constitutive form), hsp90 and hsp110 were induced in both cell lines. However, thermotolerance as defined by clonogenic survival was induced in both cell lines to a similar extent by the conditioning treatments. When cells were made thermotolerant by conditioning heating at 45 degrees C for 15 min, the inhibition of protein synthesis after challenge (second) heating was less in NRK cells than in 39-1 cells. This indicated that the extent of 'translational thermotolerance' was much higher in NRK cells than in 39-1 cells. From these results, it is suggested that the synthesis of inducible hsp70 is involved in the translational thermotolerance rather than the development of thermotolerance as defined by clonogenic survival. PMID- 1607739 TI - Effect of hyperthermia on the formation and removal of DNA interstrand cross links induced by melphalan in primary cultures of human malignant melanoma. AB - In an attempt to elucidate possible mechanisms responsible for the synergistic interaction between hyperthermia and melphalan observed in melanoma cells, we investigated the effect of heat on the formation and removal of melphalan-induced DNA interstrand cross-links (DNA ISC). Cells obtained from melanoma nodal metastases of 15 patients were grown as monolayer primary cultures and their malignant nature was confirmed by specific monoclonal antibodies. Cultures were treated with melphalan for 1 h at 37 or 42 degrees C and DNA ISC were determined by alkaline elution after proteinase K digestion. Results showed an enhanced induction of DNA ISC at hyperthermic conditions. Median number of DNA lesions 6 h after treatment was significantly higher for samples treated at 42 degrees C than for those treated at 37 degrees C (185 compared with 95 rad equivalents, p = 0.01). Moreover, the concomitant hyperthermic treatment prevented the long-term removal of DNA ISC produced by melphalan in most of the tumours considered. PMID- 1607740 TI - Effects of hyperthermia and membrane-active compounds or low pH on the membrane fluidity of Chinese hamster ovary cells. AB - Chinese hamster ovary (CHO) cells heated in the presence of the membrane-active agents procaine, ethanol, butylated hydroxytoluene (BHT) and glycerol were analysed for changes in fluorescence polarization of the lipid probe (1 [4(trimethylamino)phenyl]-6-phenyl-1,3,5-hexatriene, an indicator of plasma membrane fluidity). Cells were heated in normal and acid (pH 6.6) medium. Procaine, ethanol, BHT and low pH sensitized cells to heat-killing. Procaine, ethanol and BHT decreased fluorescence polarization (increased plasma membrane fluidity) significantly. Polarization distributions for cells heated with these sensitizers were broadened substantially and were skewed toward lower polarization values. Glycerol, a heat-protector, inhibited changes in fluorescence polarization due to heating at temperatures up to 45.0 degrees C. Heating cells at either 42 or 45 degrees C in pH 6.6 medium had no significant effect on the fluorescence polarization compared with controls, while survival was reduced substantially. Thus, heat-sensitization of low pH cannot be ascribed to changes in membrane fluidity. The changes in membrane fluidity caused by other sensitizers and protector indicate that membrane fluidity changes may be a contributing cause of cell killing by hyperthermia. PMID- 1607741 TI - Experimental thermoradiotherapy of human tumour xenografts in nude mice: design of the hyperthermia system. AB - An experimental thermoradiotherapy study was started in 1986. For this study a hyperthermia system was developed for the heating of human tumours xenotransplanted into nude mice. Our treatment device was a four-channel computer controlled hyperthermia system. Temperature was monitored by microwave radiometry at 3 GHz. Specifications of the radiometer were first evaluated under reference conditions, then thermal dosimetry was studied using non-invasive measurement of the brightness temperature TOR. Hyperthermia treatments were simulated in phantom material with radiometric monitor values TR of 40 and 41. In conjunction with the parameters of brightness temperature TOR, surface temperature TO and water bolus temperature TW thermal modelling was performed. Finally, we studied the influence of a perfused phantom to the microwave thermometry. PMID- 1607743 TI - Estimation of temperature artifact from a short interruption in ultrasonic power. AB - An error in temperature measurement, commonly referred to as a temperature artifact, frequently occurs during ultrasound hyperthermia as a result of viscous and absorption heating of the thermometer probe. At the present time there is no convenient method for correcting the clinical data for this error, which can be 0.5 degrees C, or greater. A technique is described by which the artifact can be estimated from a 10-s interruption in ultrasonic power. This technique is based on the observation that thermal decay recorded by a probe can be represented by the summation of two exponential decay rates, one of which represents the decay of tissue temperature and other decay of the artifact. Temperature drop during the first 10 s arises primarily from decay of the artifact because its time constant is approximately 7 s whereas that of the tissue generally ranges from 100 to 1000 s. A relationship between artifact and temperature drop derived from clinical data shows that the artifact is directly proportional to temperature drop. This relationship can be used to estimate the artifact during therapy if power is interrupted for 10 s. Because the interruption in power is brief, it is feasible to sample the artifact periodically during therapy and to make an on line correction for the temperature artifact. PMID- 1607742 TI - Induction of thermotolerance and heat-shock protein synthesis during nutritional deprivation. AB - Under various conditions of heating, H35 cells were submitted to acute nutritional deprivation by omitting a number of substrates (L15D medium). At 37 degrees C cell death starts after a lag-period of 3-5 h. During hypothermia cell death is delayed, whereas during hyperthermia it is accelerated especially as a result of thermosensitization. In L15D the ATP level decreases approximately 3 times faster in combination with hyperthermia than at 37 degrees C. In non thermotolerant cells thermosensization is very high at 41 degrees C and decreases with increasing temperature; in thermotolerant cells it is comparatively decreased at 41 degrees C and increased at 42.5 degrees C and above. In response to a heat shock of 30 min at 42.5 degrees C only 10% of the cell population expresses acute thermotolerance after incubation at 37 degrees C in L15D as compared to nearly 100% in complete medium (L15C). Chronic development of thermotolerance appears to be even more repressed in the presence of L15D, which partly explains the high thermosensitization at 41 degrees C. Changes in the rate of protein synthesis for combinations of nutritional deprivation and hyperthermia show a correlation with the cell survival data. Development of acute thermotolerance in L15D is accompanied by an increase in heat-shock protein synthesis relative to total protein. At 41 degrees C in L15D no heat-shock protein induction could be detected. Of the omitted substrates only glutamine can effectively abolish thermosensitization and the effects of L15D on protein and heat-shock protein synthesis depending on the condition of the cells, thermotolerant or non-thermotolerant, and to a different extent for the various proteins considered. PMID- 1607744 TI - Some practical notes on documentation of superficial hyperthermia treatment. AB - A detailed and accurate documentation of the treatment setup of each individual hyperthermia session is extremely important for retrospective data analysis as well as treatment quality control. In this paper the relatively simple and cheap documentation system developed by the Hyperthermia Department of the Dr Daniel den Hoed Cancer Center, is presented. PMID- 1607746 TI - [Growth-inhibitory factor and Alzheimer's disease]. PMID- 1607747 TI - [N-Acylethanolamine phospholipids in mammalian cells]. PMID- 1607745 TI - [Chimeric collagens: functional modulators for major collagen fibrils]. PMID- 1607748 TI - [Physiological significance of epidermal growth factor in fetal maturation and placental growth in mice]. AB - To elucidate the physiological significance of epidermal growth factor (EGF) in fetal and placental development, the effects of neutralization of circulating EGF by anti-EGF antiserum on fetal and placental development were evaluated in pregnant mice. Abdominally administrated antiserum neutralized EGF in fetal and maternal circulation. Fetal weight was not affected by anti-EGF antiserum, but placental weight was suppressed when antiserum was administrated in the latter half of pregnancy. There was no significant difference between control and antiserum injected mice in the affinity and capacity of EGF receptor in the placenta. The number and volume of lamellar bodies were significantly decreased in antiserum treated mice at Day 10-18 compared to control mice. These results suggest that EGF is involved in placental development, especially in late pregnancy. Furthermore, EGF in the circulation may contribute to enhancing fetal lung maturity rather than fetal growth. PMID- 1607749 TI - [Effect of dietary supplementation with eicosapentaenoic acid on surgically induced endometriosis in the rabbit]. AB - The association between endometriosis and infertility is well known. Recently some investigators have speculated that endometriosis may cause an inflammatory response and prevention of normal fertilization, embryo development or implantation. Eicosapentaenoic acid (EPA) inhibits production of cyclooxygenase metabolites of arachidonic acid (AA). The effect of oral administration of pure EPA on endometriosis was studied. The author supplemented the diet of Japanese white rabbits with EPA (100 mg/kg/day, experimental group) or with a 5% gum arabic solution (control). Endometriosis was surgically induced by a previously described experimental technique. Peritoneal fluid PGE2, PGF2-alpha and IL-1-beta concentrations in the experimental rabbits and controls were measured before and after induction of endometriosis by laparotomy. Following the treatment, EPA levels in plasma and peritoneal fluid increased significantly. However, no differences were seen in AA levels. Peritoneal fluid PGE2 and IL-1-beta concentrations increased significantly after induction of endometriosis in the control group. In contrast, they were not significantly changed after endometrial implantation in the experimental group. Peritoneal fluid PGF2-alpha concentrations were lower in the EPA group than in the controls, but there were no significant differences. The findings of the present study suggest the beneficial effects of EPA in the therapy of infertile patients with endometriosis. PMID- 1607750 TI - [Changes in blood pressure in two types (absolute and relative) of pregnancy induced hypertension (hypertensive type of toxemia)]. AB - The criteria for pregnancy induced hypertension (PIH: hypertensive type of toxemia) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute PIH (A-PIH)" diagnosed by (1) systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than 160 mmHg or (2) diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg. The other one is "relative-PIH (R-PIH)" diagnosed by (3) an increase in SBP greater than or equal to 30 mmHg compared to the usual SBP or (4) an increase in DBP greater than or equal to 15 mmHg compared to the usual DBP (In this paper, blood pressure prior to the 12th gestational week is considered as "usual" blood pressure). However, there has been no report in which two types of PIH are assessed. Our hypothesis is that the pathophysiology of the two types of PIH is different. We have already reported the clinical background of two types of PIH. The purpose of this study is to clarify the pathophysiological difference by evaluating the blood pressure change during pregnancy. We evaluated 963 nullipara and 747 multipara whose pregnancies were recorded from the 1st trimester (multiple pregnancy and pre-term delivery before the 32nd gestational week were excluded). Among the nullipara, 765 women (79.4%) were diagnosed as having normal blood pressure (N-group), 7.1% as A-PIH, and 13.0% as R-PIH. Among the multipara, the N-group consisted of 632 women (84.6%), the A-PIH: 4.6% and R PIH: 10.3%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607752 TI - [Qualitative assessment and characterization of CA125 antigen produced from human endometrial epithelial cells]. AB - We have established an in vitro system in which epithelial cells (EC) and stromal cells (SC) from the human endometrium are placed in culture to examine the production of CA125. There was a much greater amount of CA125 in heterotopic EC after culture cells reached confluence than during the logarithmic growth phase. Heterotopic EC in culture secreted nine times as much CA125 constitutively after reaching confluence as eutopic EC. Flow cytometry (FCM) analysis indicated that the changes in CA125 expression correlated with the cell cycle. The CA125 expression was mainly observed in the G0/G1-phase in the cell cycle. There was no amplification of the CA125 expression in heterotopic EC membranes. The results of SDS-PAGE and Western blot indicated that the 110 KDa molecule of CA125 might be specific for adenomyosis. The biochemical and physical nature of CA125 was examined to characterize the antigenic determinant of this antigen. These results strongly suggested that the CA125 antigenic determinant from EC was composed of conformationally dependent peptides. We conclude that significantly increased secretion of CA125 from heterotopic EC could be attributed to the increase in serum CA125 in patients with adenomyosis. PMID- 1607753 TI - [Effect of cervical mucus on zona induced acrosome reaction of human spermatozoa]. AB - Zona induced acrosome reaction of human spermatozoa was examined by FITC labelled PSA staining. When human spermatozoa were incubated with salt stored human eggs for 6 hours, the percentage of acrosome reacted spermatozoa was 35.7 +/- 17.7%. The zona induced acrosome reaction rate was significantly higher than that of the spontaneous acrosome reaction (2.8 +/- 1.9%). These date indicate that the zona pellucida of the human egg have the ability to induce the acrosome reaction as in other mammalian zona. Additionally the effect of cervical mucus on the acrosome reaction was examined. Spermatozoa which passed through the cervical mucus were collected and examined for the rate of spontaneous and zona induced acrosome reaction. The rate of spontaneous acrosome reaction was almost the same as the control, but the rate of zona induced acrosome reaction (51.6 +/- 6.8%) was significantly higher than that of the control (25.6 +/- 9.4%). These data suggest that spermatozoa appear to complete capacitation by passing through cervical mucus. PMID- 1607751 TI - [Fetal growth in two types (absolute and relative) of pregnancy induced hypertension (hypertensive type of toxemia)]. AB - The criteria for pregnancy induced hypertension ("PIH" which is a hypertensive type of toxemia) have been determined by the Japanese Obstetrics and Gynecology Society. Mild PIH is classified into two types. One is "Absolute PIH (A-PIH)" diagnosed by (1) systolic blood pressure (SBP) greater than or equal to 140 mmHg and less than 160 mmHg or (2) diastolic blood pressure (DBP) greater than or equal to 90 mmHg and less than 110 mmHg. The other one is "relative-PIH (R-PIH)" diagnosed by (3) an increase in SBP greater than or equal to 30 mmHg compared to usual SBP or (4) an increase in DBP greater than or equal to 15 mmHg compared to usual DBP (In this paper, blood pressure prior to the 12th gestational week is considered as "usual" blood pressure). We have already investigated the pathophysiological difference through the background and the change in blood pressure throughout pregnancy and puerperium in these two types of PIH. The purpose of this study is to clarify the pathophysiological difference by evaluating the influence of hypertension on fetal growth. We evaluated 963 nullipara and 747 multipara whose pregnancies were recorded from the 1st trimester (multiple pregnancy and pre-term delivery before the 32nd gestational week were excluded). Among nullipara, 765 women (79.4%) were diagnosed as having normal blood pressure (N-group), 7.1% as A-PIH, and 13.0% as R-PIH. Among multipara, the N-group consisted of 632 women (84.6%), A-PIH: 4.6% and R-PIH: 10.3%. There is no difference among the three groups in gestational days but the body weight, the chest circumference, and the abdominal girth at birth of A-PIH show a significant difference from those of the R-PIH and N-groups in both nullipara and multipara.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607754 TI - [The study of ovarian metastasis in uterine cancer]. AB - The correlation between histological ovarian metastasis and histologic cell type, clinical stage, depth of invasion, lymph node metastasis, and menstrual activity were analyzed in 566 patients who underwent surgery for uterine cancer at the hospital of Niigata University between January, 1971 and May, 1990. Ovarian metastasis was studied in 456 patients with stage Ib or more advanced cervical cancer and 110 patients with stage Ia or more advanced endometrial cancer. The following results were obtained: 1. The incidence of ovarian metastasis of cervical cancer by histologic cell type was 18.6% (8/43) for adenocarcinoma, 6.7% (1/15) for mixed type adenocarcinoma and squamous cell carcinoma, and 0% (0/398) for squamous cell carcinoma. The metastasis rate in patients with endometrial carcinoma was 10.8% (10/93) for adenocarcinoma, but there was no metastasis of 2 squamous cell carcinoma, 13 mixed type of adenocarcinoma and squamous cell carcinoma or 2 undifferentiated carcinoma. 2. The incidence of metastasis of cervical adenocarcinoma by stage was 5.3% (1/19) for stage Ib and 29.2% (7/24) for stage II. The metastasis rate of mixed type of adenocarcinoma and squamous cell carcinoma was 0% (0/6) for stage Ib and 11.1% (1/9) for stage II. The incidence of metastasis of endometrial carcinoma was 2.1% (1/47) for stage Ia, 15.0% (3/20) for stage Ib, 15.0% (6/40) for stage II and 0% (0/3) for stage III. 3. All the patients with ovarian metastases of uterine cervical cancer had invasion to a depth of more than 2/3 of the uterine cervix, while the incidence of ovarian metastasis of endometrial carcinoma was increased with deep invasion of the uterine muscular layer, and metastasis was present even in shallow invasion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607755 TI - [Effect of maternal exercise with graded treadmill on fetal heart rate]. AB - The effect of maternal exercise on the fetal and maternal heart rate was studied in 10 normal pregnant women in their third trimester. They participated in 15 minute graded treadmill exercise. Fetal heart rate (FHR), uterine contraction, maternal blood pressure, electrocardiogram, and oxygen consumption were monitored, before, during, and after exercise. FHR could be monitored in 7 women. Maternal maximal heart rate ranged from 143 to 168 bpm which approximated 61% to 84% training intensity. FHR showed a significant rise in 4 women during exercise. Of four cases which showed more than 70% training intensity, 3 demonstrated fetal tachycardia over 160 bpm and one demonstrated fetal bradycardia under 120 bpm. The baseline fetal heart rate remained from 120 bpm to 160 bpm in cases under 70% training intensity. There was no pathological deceleration and the variability was preserved in all cases. It is suggested that maternal exercise intensity should be less than 70% of the patient's maximal capacity, which approximates maternal heart rate of about 150 bpm. PMID- 1607756 TI - [The determination of basic fibroblast growth factor (bFGF) in human placental tissue and the changes in bFGF during pregnancy]. AB - The purpose of this study is to develop an assay system for quantification of bFGF in human tissue and to investigate the changes in bFGF content in the human placenta during pregnancy. Sixty-two placental tissue samples from various stages of normal pregnancies were collected. Approximately 28 micrograms bFGF was obtained per 1 kg of placental tissue. The recovery rates were 17.1 +/- 7.4%. The purified samples were confirmed as bFGF by SDS-PAGE and enzyme-linked immunoelectrotransfer blot (EITB) with anti-human bFGF monoclonal antibody. The bFGF readings in the human placenta determined by RIA were 11.81 +/- 2.11 fmol/mg protein (first trimester), 20.45 +/- 4.85 (early second trimester), 9.52 +/- 5.02 (late second trimester), 7.41 +/- 2.07 (third trimester), and 7.75 +/- 1.86 (post trimester). The placental bFGF were significantly high in the early stage of second trimester and declined gradually during the remainder of the pregnancy. The RIA values were correlated closely with the values obtained by bioassay. These results demonstrate that our assay system provides a tool for the quantification of bFGF in biological samples and suggest that bFGF, the active mitogen and angiogenic factor, participates in the formation of the human placenta. PMID- 1607757 TI - [Immunohistochemical study of collagen type III in adenomyosis]. AB - To clarify the mechanism of the origin of adenomyosis, we investigated the immunohistochemical distribution of collagen type III in the human endometrium and the adenomyosis throughout the menstrual cycle. 1) Collagen type III was localized in the stroma of normal endometrium and ectopic endometrium, and in the myometrium. No staining of collagen type III was observed in the endometrial gland. 2) The intensity of staining for collagen type III in the basal layer of normal endometrium was stronger than those in the functional layer. The staining in the proliferative phase was stronger than that in the secretory phase. 3) The intensity of staining of collagen type III in ectopic endometrium paralleled that in the basal layer of normal endometrium. 4) The intensity of staining of collagen type III in the myometrium did not change throughout the menstrual cycle. These results suggest that close similarities exist between stromal cells in normal endometrium and in ectopic endometrium from the viewpoint of the extracellular matrix. PMID- 1607758 TI - [Immunohistological study on HLA class II antigen expression and lymphocyte infiltration in cancer tissues of the uterine cervix]. AB - The correlation between the presence and absence of HLA Class II antigen and stromal lymphocyte infiltration in cervical cancer tissue was analyzed immunohistologically. The correlation was also studied in relation to the prognosis of patients with cervical carcinoma. Immunohistological staining was performed with a monoclonal antibody differentiating monomorphic determinants of HLA-DR and an antibody (HU-30) differentiating HLA-DR1/2, one of the polymorphic determinants, in 36 patients with cervical carcinoma. Infiltrating lymphocytes were identified immunohistologically with various monoclonal antibodies, and the following results were obtained: 1) Twenty-six (72.2%) of the 36 patients were evaluated as positive for HLA-DR1/2 from the reaction with HU-30. 2) Cancer cells from 21 (80.8%) of the 26 patients were HLA-DR positive, while those from 5 (19.2%) were HLA-DR negative. 3) Cancer cells from 12 (46.2%: group A) of the 21 patients were also positive for HLA-DR1/2, while those from 9 (34.6%) were negative for the determinant. 4) There was no patient whose stromal lymphocytes were negative for HLA-DR1/2 and whose cancer cells alone were positive for the determinant. Thus, there was a total of 14 patients (53.8%: group B) whose cancer cells were negative for HLA-DR. 5) The lymphocytes that infiltrated the area surrounding the cancer lesion were mainly T cells, with Leu-3a cells (helper/inducer T cell) more abundant than Leu-2a cells (suppressor/cytotoxic T cell). 6) Infiltration of T cells, the subgroup and IL-2-receptor-positive cells was greater in group A than in group B.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607759 TI - [Expression and bioactivity of refined recombinant oxytocin-like substance obtained from human placental cDNA library]. PMID- 1607760 TI - [Measurement of intracellular [Ca]2+i concentration in cultured human cytotrophoblast using fura-2 fluorescence]. PMID- 1607761 TI - [The role of magnetic resonance imaging in the evaluation of ovarian tumors in pregnancy]. PMID- 1607762 TI - [Three cases of postpartum infection with methicillin-resistant Staphylococcus aureus (MRSA)]. PMID- 1607763 TI - [Significance of 5-S-cysteinyldopa on primary malignant melanoma of the female genital organs]. PMID- 1607765 TI - [Ectopic pregnancy and antibodies of Chlamydia]. PMID- 1607764 TI - [A case of ovarian cancer complicated with meningitis carcinomatosa]. PMID- 1607766 TI - [Prediction of sperm fertilizing potential by sperm survival test for severe oligospermic patients]. PMID- 1607767 TI - [Primary amenorrhea and hirsutism associated with hyperinsulinemia type A]. AB - Hyperinsulinemia type A, which is a very rare disease, is often manifested in menstrual disorders and/or anovulation. Recently, a 19-year-old woman diagnosed with hyperinsulinemia and acanthosis nigricans, visited our outpatient clinic complaining primarily of amenorrhea and hirsutism. Endocrinological studies revealed normal LH and FSH levels, low estradiol (42.3pg/ml) and high androgens (testosterone: Over 150ng/ml, delta androstenedione: 4.8ng/ml) in serum. Her fasting insulin level was excessively high (over 320 microU/ml). UST showed bilateral polycystic ovaries. These data support the hypothesis of a pathogenic mechanism of ovarian dysfunction in patients with hyperinsulinemia; that is, too much insulin stimulates ovaries directly, followed by the production of androgens and the formation of polycystic ovaries. Strict dietary management of this patient failed to cause spontaneous vaginal bleeding. Progesterone administration did not cause withdrawal vaginal bleeding. These findings suggest that the higher that insulin level is, the more difficult it is to induce ovulation. PMID- 1607768 TI - [Characterization of two novel cell lines established from a single human uterine cervical adenocarcinoma, and their chemosensitivities and hormonal effects on their proliferation]. AB - Two new cell lines were established from a single human uterine cervical adenocarcinoma which had been successfully transplanted into nude mice. They were subcultivated more than 70 times over a period of 46 months and designated as TCO 1 and TCO-2, respectively. Growth characteristics, modes of chromosomes and specific tumor makers were different in TCO-1 and TCO-2. The plating efficiency of TCO-1 was greater and its doubling time was shorter than those of TCO-2. Modes of chromosomes were 77 in TCO-1 and 94 in TCO-2. Their chemosensitivities to 13 anticancer drugs were studied by MTT assay. Only the mitomycin C (MMC) was an effective agent for both TCO-1 and TCO-2 cell lines which were characteristically different from each other. The results suggest that MMC would be a promising agent for chemotherapy of human uterine cervical adenocarcinoma. The influences of 6 hormones (estradiol, progesterone, dihydrotestosterone, medroxyprogesterone acetate, human menopausal gonadotropin, human chorionic gonadotropin) on their proliferation were studied by MTT assay and dye exclusion assay. TCO-1 and TCO-2 showed no significant changes in proliferation in any of them. It is suggested that hormone replacement therapy could be indicated even for postoperative patients with cervical adenocarcinoma. PMID- 1607769 TI - [The evidence of safety of immunotherapy for unexplained habitual aborters]. AB - Immunotherapy (immunization twice at 5 and 7 weeks of gestation with X-irradiated 200ml total blood or 1-200 x 10(6) mononuclear cells from the husband) was performed on 200 women without autoimmune abnormalities but experiencing habitual abortions of unknown causes between August, 1982 and September, 1990. One hundred fifty-seven babies were eventually born alive. The oldest offspring was 7 yrs 4 mos in August, 1991. We investigated the safety of the immunotherapy in terms of its effects on the women, conditions during pregnancy/labor and conducted long term follow-up on offspring. Among 190 women whose pregnancy terminated by September, 1990, 152 cases gave birth, including 5 sets of twins. The successful rate was 80.0%. There were no complications among the 200 cases, only 2 small-for dates babies (1.3%) among 157 babies born alive, and 1 baby born dead in the 3rd trimester, but that was not directly related with immunotherapy. Tsumori-Inage Infant Mental Development Test found no abnormalities (3 yrs and over). At 3 yrs, and only 1 child scored under the mean--2 standard deviation in height and weight. Thus, the safety of the immunotherapy was confirmed by long-term follow up of both mother and child in which no notable complications resulting from immunotherapy with the husband's X-irradiated cells could be found. PMID- 1607770 TI - [Transvaginal ultrasonographic assessment of endometrium during hMG-hCG cycles]. AB - Daily changes in the thickness and texture of the endometrium were assessed by transvaginal sonography in 15 natural (cycles 'cycle-A) and 24 stimulated cycles (cycle-B: hMG-hCG cycles; hCG 10,000 IU was injected on the day after the dominant follicle reached 18mm in three-directional radius, n = 7) (cycle-C: hCG 3,000 IU injections on the 5th, 9th and 13th day after hCG 10,000 injection were added to cycle-B, n = 10) (cycle-D: hCG 1,000 IU instead of 3,000 IU of cycle-C, n = 7). The duration of the luteal phase was 15, 9, 17 and 18 days in cycle-A, cycle-B, cycle-C and cycle-D, respectively. The thickness of the endometrium increased lineally until ovulation day (D +/- 0) (thickness: 10.7mm) in cycle-A, but in stimulated cycles it revealed a significantly rapid increase until D-4 (10.9mm) and then reached a plateau. The ratio of the thickness of the hyperechoic area to the total thickness of the endometrium reached 100% (D + 9) in cycle-A. The ratio reached only 72% (Max, D + 4) in cycle-B, but the effect of luteal support was shown to reach 89% and 85% (Max, D + 7) in cycle-C and cycle D. The serum progesterone level in stimulated cycles revealed a rapid increase until D + 5, but it had an unstable pattern in cycle-C and cycle-D. It was shown that luteal support was necessary to offset the luteal phase defect caused by stimulation with hMG. PMID- 1607771 TI - [Changes in steroid enzyme activities with age in human ovary]. AB - It is well documented that sex hormone secretion decreases as age advances. In this study, 17 alpha-hydroxylase (17hy), 20 alpha(beta)-hydroxy steroid dehydrogenase (20-HSD), C17-20 lyase, 17 beta-hydroxy steroid dehydrogenase (17 beta-HSD) and aromatase activities in ovarian tissues were examined in order to study the changes in steroid metabolism in human ovary with age. Tissues were obtained from women aged 30-81 years who had undergone gynecological laparotomy. Enzyme activities were measured by the conversion of 14C-labeled progesterone, 17 alpha-hydroxy progesterone and androstenedione to amounts of corresponding labeled products. Remarkable reduction of C17-20 lyase and 17hy activities were noticed in the ovaries obtained from the women in the premenopausal stage when the activities were compared with those from reproduct women. However, the activities of aromatase, 17 beta-HSD and 20-HSD were not changed. Further, a decrease of 17hy activities was observed in the ovaries obtained from menopausal women. Aromatase activity was also reduced at this stage while the 17 beta-HSD and 20-HSD remained unchanged. In addition, the formation of 17 alpha, 20 beta-OH P4 from 17P4 was first demonstrated indicating that activity of 20 beta-HSD in postmenopausal ovary and found to be localized in the microsomal fraction. These result indicated that the changes of ovarian steroid enzyme activities with age were characterized by a striking reduction in C17-20 lyase and 17hy activities while 17 beta-HSD and 20-HSD activities were not impaired. Aromatase activity was found to be decreased in ovaries at menopause. PMID- 1607772 TI - [Clinicopathological and histochemical study of adenoma malignum of the uterine cervix]. AB - A clinicopathological and histochemical study has been made on ten cases of adenoma malignum of the cervix. The clinical symptoms and signs of the ten cases were vaginal discharge, vaginal bleeding, and hypertrophy of the cervix. The Papanicolaus classification of the initial smear test obtained by scraping was class III in six cases, class V in two, class IV in one and class II in one. The columnar cells of adenoma malignum showed a weak or negative reaction to high iron diamine (HID) stain and negative to Alcian blue (AB) stain. Normal endocervical columnar cells showed a positive reaction to HID stain and a negative reaction to AB stain. CEA antigen was present in the columnal cells of the adenoma malignum, although normal endocervical glands did not contain CEA. PMID- 1607773 TI - [The role of signal transduction systems in the regulation of production and secretion of TA-4 by cultured cervical epidermoid carcinoma cells (CaSki)]. AB - The CaSki cell line derived from an epidermoid carcinoma of the uterine cervix produces and releases a tumor associated-antigen, TA-4. The authors have already reported that EGF stimulated the production and secretion of TA-4 by the CaSki cells. EGF receptor is known to be one of the proteins phosphorylated by C kinase. In order to elucidate a possible role of signal transduction systems (cAMP-A-kinase, diacyglycerol-C-kinase and Ca(2+)-calmodulin) in the regulation of TA-4 production and secretion by human cervical epidermoid carcinoma cells, the effects of cholera toxin (CT), an activator of adenylate cyclase, phorbol 12 myristate 13-acetate (PMA), a protein kinase C activator, and Ca2+ ionophore A23187, an activator of Ca2+ modulation on TA-4 production and secretion by CaSki cells were evaluated. TA-4 in the cultured cells and media were measured with a SCC RIA-Kit. The addition of PMA or Ca2+ ionophore to the medium caused increases in the cellular levels of TA-4 and TA-4 levels in the medium in a dose-dependent manner shortly after the addition. Combined treatment with PMA and Ca2+ ionophore did not cause additive increases in TA-4 levels in the cells and medium compared to the treatment with PMA alone or Ca2+ ionophore alone.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607774 TI - [An analysis on prognostic significance of histopathologic risk factor in uterine endometrial carcinoma]. AB - Prognostic risk factors in histopathologic findings were analyzed in the data for one hundred and thirteen patients with uterine endometrial carcinoma who were treated surgically. Univariate survival analysis with Kaplan-Meier methods revealed that the nuclear grade (p less than 0.005), lymph-vascular space invasion (p less than 0.005), histologic grade (p less than 0.01) and histologic type (p less than 0.01) correlated with the patient's prognosis. Among surgical FIGO stages II and III, there was similar significance in the correlations in the nuclear grade (p less than 0.05), lymph-vascular space invasion (p less than 0.0001) and histologic type (p less than 0.05), although there was difference (p less than 0.05) only between grade 1 and grade 3 in the histologic grade. Multivariate survival analysis with a proportional hazard regression model showed that the nuclear grade (p less than 0.005) and lymph-vascular space invasion (p less than 0.01) correlated significantly with the prognosis. The hazard ratios with a 95% confidence interval for each of these factors were 19.2 (3.2-115.7) and 16.9 (2.1-135.3), respectively. The 3-year survival rate was 98% for a hazard ratio less than 64.7, and 45% for one more than 67.4, between which there was a significant difference (p less than 0.0001). And univariate survival analysis of this hazard ratio also revealed strong correlations with the patient's prognosis. These results suggest that it is of great importance to adopt the hazard model including such factors as the nuclear grade and lymph-vascular space invasion in estimating the patient's prognosis and proceeding to adequate post-operative therapy for individual patient. PMID- 1607775 TI - [Morphological and immunohistochemical study of the placental villi in pregnancy complicated by systemic lupus erythematosus]. AB - In 25 cases of pregnancy complicated by SLE, we examined the relationships between fetal growth and histopathological findings in the placental villi. The following results were obtained. 1. As for histological findings in the placenta, in most cases clear findings of circulatory disorders were obtained. 2. In the light microscopic visual field at x63, no difference was observed among the group in the cross section occupying rate of the villi and cross section area of the terminal villi, but in one case in the IUFD group, the villi were underdeveloped and the cross section occupying rate of the villi was low. 3. The villous/vascular cross section area ratio per single terminal villus became smaller in the following order: full term AFD group, full term SFD group, premature AFD group, and premature SFD group, and a significant difference was observed between the normal controls and the premature SFD group. 4. During immunoglobulin staining by the PAP method, IgG deposits were observed in the villous syncytiotrophoblasts and their periphery, in vascular endothelial cells in the villi, and in the villous interstitium, etc. in both the SLE cases and the normal controls, but deposits of IgM in the same regions were observed only in the premature SFD group of pregnancies complicated by SLE. PMID- 1607776 TI - [A case of pregnancy with Budd-Chiari syndrome]. PMID- 1607777 TI - [Changes in various differentiation-related makers after differentiation induction of a pluripotent human embryonal carcinoma (EC) cell line by hexamethylene bisacetamide (HMBA)]. PMID- 1607778 TI - [Recent progress on study of peripheral nervous system diseases]. PMID- 1607779 TI - [Progress in diagnosis of neuropathies with selective symptom of motor nerve disturbances]. PMID- 1607780 TI - [Progress in diagnosis of neuropathies with selective symptom of superficial sensory nerve disorders]. PMID- 1607781 TI - [Progress in diagnosis of cranial neuropathies]. PMID- 1607782 TI - [Plasma exchange therapy of Guillain-Barre syndrome]. PMID- 1607783 TI - [Case of paroxysmal cold hemoglobinuria]. PMID- 1607784 TI - [Case of aortitis syndrome diagnosed by MRI]. PMID- 1607785 TI - [Case of IgM-lambda type M proteinemia with a high titer of rheumatoid factor]. PMID- 1607787 TI - [Current status of lung transplantation]. PMID- 1607786 TI - [Case of thyroid crisis effectively treated with a urianry tract angiographic medium]. PMID- 1607788 TI - [HIV infections]. PMID- 1607789 TI - [Therapy of liver cirrhosis]. PMID- 1607790 TI - [Imaging diagnosis of biliary tract neoplasms]. PMID- 1607791 TI - [Non-invasive therapy of gallstones]. PMID- 1607792 TI - [Extracorporeal shock wave lithotripsy therapy of patients with gallstone]. PMID- 1607793 TI - [Diagnosis of early-stage pancreatic neoplasms]. PMID- 1607794 TI - [Calcium metabolism disorders and the basic diseases--special reference to serum calcium imbalances]. PMID- 1607795 TI - [Clinical therapy and diagnosis of diabetes mellitus]. PMID- 1607796 TI - [Physiopathology and therapy of systemic lupus erythematosus]. PMID- 1607797 TI - [Diagnosis and therapy of rheumatoid arthritis]. PMID- 1607798 TI - [Clinical study on inflammatory bowel diseases]. PMID- 1607799 TI - [Epidemiology and clinical study of virus hepatitis]. PMID- 1607800 TI - [ESWL therapy of patients with gallstone]. PMID- 1607801 TI - [Diagnosis and therapy of vascular dementia]. PMID- 1607802 TI - [HTLV-I-associated myelopathy]. PMID- 1607803 TI - [Problems in diagnosis and therapy of angina pectoris]. PMID- 1607804 TI - [Physiopathology and therapy of patients with hypertension]. PMID- 1607805 TI - [Drug therapy of patients with arrhythmia]. PMID- 1607806 TI - [Treatment of patients with chronic kidney failure]. PMID- 1607807 TI - [Diagnosis of glomerulonephritis]. PMID- 1607808 TI - [Respiratory tract infections in the aged]. PMID- 1607809 TI - [Diagnosis and therapy of chronic pulmonary emphysema]. PMID- 1607810 TI - [Oxygen inhalation therapy of respiratory failure]. PMID- 1607811 TI - [Clinical study of leukemia]. PMID- 1607812 TI - [Guideline for bone marrow transplantation]. PMID- 1607814 TI - [Fever of unknown origin]. PMID- 1607813 TI - [Methicillin resistant Staphylococcus aureus]. PMID- 1607815 TI - [Studies on matrix components relevant to structure and function of the temporomandibular joint]. AB - Proteoglycans (PGs), or their component glycosaminoglycan (GAG) chains, have long been recognized as small in quantity but as significant components for many connective tissues. The temporomandibular joint (TMJ) disc and synovial fluid were rarely investigated in this regard. This research was aimed at the biochemical analysis of the composition of collagen, GAGs and PGs in the normal human and porcine TMJ discs, and of PGs in the synovial fluid. 1. The collagen type analysis by gel electrophoresis revealed that the human and porcine TMJ discs were composed only of type I collagen. 2. The human TMJ disc contained 69.9% chondroitin sulfate, 24.5% dermatan sulfate, 5.6% hyaluronic acid and a trace amount of keratan sulfate, and the porcine TMJ disc, 5.8%, 91.4%, 2.8% and a trace amount, respectively. Immunohistochemical staining of the functional parts of the TMJ disc showed a universal distribution of these GAGs. 3. PGs were extracted from the TMJ disc with 4 M guanidine chloride and separated by ion exchange and gel-filtration chromatography. A high molecular weight PG resembling the cartilage PG and two low molecular weight PGs having a core protein of Mr 40 K were isolated. 4. PGs suggested to be derived from the matrix of other tissues were found in the abnormal human synovial fluid. From these results it was suggested that the TMJ disc was thought not to be fibrocartilage but a fibrous tissue adapted against to the compressive and tensile force. PMID- 1607817 TI - [Study on analysis of viscoelastic property of palatal mucoperiosteum--about the creep recovery]. AB - The purpose of this study was to analyze the creep phenomena of the palatal mucosa under pressure and after pressure release. The measuring device consisted of the control box, which regulated the loading force by air pressure, and the pick-up, which was fixed to the teeth and applied the load onto the mucosa, detected the displacement of the mucosa. The creep was analyzed by the Voigt 4 element model. The ratio of the recovery (S1'/S1, S2'/S2) and the recovery percentage were analyzed on the creep after the pressure release and evaluated from the point of expressing exactly the viscoelastic recovery. The results were as follows: 1. Both the amount of the displacement under pressure and the recovery of the palatal mucosa showed the least value at the center site and at the other sites less at the distal site than the mesial site. 2. The ratio of S1'/S1 was about 0.5 at all sites. On the other hand, the ratio of S2'/S2 showed values higher than 1 except at the center site and was significantly different among the other sites. 3. It was pointed out that the recovery percentage was more suitable than the ratio of the recovery to explain the viscoelastic recovery of the palatal mucosa. PMID- 1607816 TI - [Statistical survey of prosthetic restorations--fixed and removable prosthesis]. AB - This is a continued report on the statistical classification of the prosthetic restorations placed in the outpatients in the Tokyo Medical and Dental University Hospital. The data were collected from the laboratory records during the period of January to June of 1986. The results are summarized as follows: 1. Total of 419 bridges, consisting of nearly the same number in the maxillary and mandibular units, were fabricated. A wide variety of designs was observed for those not covered by the health insurance. 2. Approximately 83% of the 265 complete dentures were covered by the health insurance. The number of the maxillary units was slightly more than that of the mandibular units, which was similar to the data collected about 20 years ago. 3. Seven hundred and fifty-four partial dentures were placed and approximately 45% of these were covered by the health insurance. 4. Various designs were observed in the 'Konus-Kronen' type of prosthesis. They were assumed to be applied not only for the restoration of the edentulous areas, but also for the splinting of the remaining teeth. 5. Fixed bridges were placed in more than 90% of the cases with single tooth loss. However, partial dentures were more frequently used than the fixed bridges for the restoration of the two-tooth loss. PMID- 1607818 TI - [Condylar displacement and mandibular bending deformation due to bite force]. AB - The purpose of this study was to investigate the influence of the difference of the biting pivot positions, vertical dimensions and mandibular positions on the condylar displacement during clenching. The condylar displacement was measured by the Pantograph using the point of condyle on the Kinematic Axis as the representative and the Path of the Kinematic Axis (PKA) as the standard for the judgement of the displacement. The bending deformation of the mandible was also measured by a multi-vision and image analyzing system in order to correct its influence on the condylar displacement measured. The results were as follows: 1. The direction and magnitude of the condylar displacement changed with the biting pivot position. The bilateral condyles moved upwards deviating from the PKA when clenching on the bilateral 2nd-molar or the bi-or unilateral canine teeth; Whereas the biting-side condyle moved downwards and the idling condyle either moved upwards deviating from the PKA or backwards along the PKA when clenching on the unilateral 2nd-molar. 2. The displacement of the idling condyle was multi directional when clenching on the habitual closure whereas it was unidirectional and of a smaller magnitude when clenching on the most retruded closure. 3. When clenching on the unilateral 2nd-molar, the mandible on the non-pivot side had an inward and upward bending deformation and the arch width decreased. It can be inferred that the actual idling condylar displacement was more inward and upward than that measured by the Pantograph. PMID- 1607819 TI - [Effects of difference of occlusal splint contacts on masticatory system]. AB - The short-term effects of the difference of occlusal splint contacts on the jaw function were investigated on five healthy subjects. The maxillary stabilization splint (S-type) was fabricated and sectioned into three parts: an anterior section (A-type) and two posterior sections (P-type). These 3 types of splints were used for 10 days for each subject. The EMG activity of the masseter and the anterior and the posterior temporal muscles were measured during the maximum clenching in the intercuspal position and on the wearing splint. Subsequently on the bite force-measuring device with two transducers the bite and the EMG activity were measured during the maximum clenching, and the intercuspal occlusal contacts were recorded. The results were as follows: 1. After wearing the P-type, the total EMG activity during clenching in the intercuspal position was decreased, then increased after removal. 2. After wearing the S-type and the A type the anteroposterior distribution of the bite force during clenching was changed, then returned after removal. 3. After wearing the A-type, the occlusal contact area of the anterior teeth in the intercuspal position was decreased, then increased after removal, while after wearing the S-type and the P-type that of the posterior teeth was decreased, then increased after removal. PMID- 1607820 TI - [Expression of hemidesmosome-associated antigen and its biochemical properties]. AB - Immunohistochemical study on the hemidesmosomes of the normal and malignant squamous epithelia of the human oral mucosa was performed using a monoclonal antibody (MoAb) 3A1 which recognized specifically the hemidesmosomes. Biochemical characterization of the antigen recognized by this antibody was also investigated. The results and conclusion of this study were as follows: 1) MoAb 3A1 reacted specifically with the hemidesmosomal plaques located on the basement membrane zone of the basal cells of the normal squamous epithelium. 2) In the cases of malignant epithelium, MoAb 3A1 reacted irregularly with the cell membrane at the border of the cell and stroma. The expression of the antigen in the carcinoma cells was found on the hemidesmosomes with abnormal structure. 3) The antigen recognized by MoAb 3A1 extracted from the cultured carcinoma cells was purified by protein A Sepharose affinity chromatography and DEAE ion-exchange HPLC. The purified antigen was a protein associated with hyaluronate having a molecular weight of more than 200 Kd. The molecular weight of the protein itself was found to be 180 Kd. Analysis of the amino acid composition showed this antigen was mainly composed of glycine, serine, alanine, glutamic acid and leucine. PMID- 1607821 TI - [Monitoring of tooth displacement using eddy-current type sensor--concerning orthodontic treatment for patients with cleft lip and palate]. AB - We frequently experienced a relapse tendency after the upper dental arch expansion in a patient with cleft lip and palate. The purpose of this study was to detect the tooth displacement right after removing the orthodontic appliance. Time-lapse monitoring of the displacement was performed on the maxillary canine in the minor segment using a non-contact eddy-current type sensor. Clinical application was tested in 9 patients with clefts, and the following results were obtained: 1) The relationship between the displacement and the output voltage of the sensor showed a good linearity with a +/- 3% standard error. 2) In 3 subjects with oronasal fistula after orthodontic treatment and in a subject with discontinuity of the maxillary dental arch, displacements toward the palatal side were recorded. 3) In 2 subjects with arch continuity in the maxilla, no significant displacement was observed. 4) The viscoelastic property of the surrounding tissue of the tested tooth could have induced the displacement monitored by this method. PMID- 1607822 TI - [Observation on structural features and characteristics of occlusal fissures and pits in human permanent molars]. AB - In a series of studies to investigate the structural features and the characteristics of the tooth, a detailed observation was made on the enamel surface and the enamel composing the fissure and pit of the freshly extracted human permanent molars, using scanning electron microscopy and transmission electron microscopy. The materials employed in this observation were taken from the noncarious surface of molars. The following results were obtained: The hypocalcified zone was observed more or less in the enamel composing the fissure and pit. In many cases, the dental cuticle can be seen on the enamel surface. A rodless enamel was present, in greater or lesser degree, in the enamel surface layer. Retzius's line was observed clearly in the enamel composing the fissure and pit. In many cases, perikyamata was found on the enamel surface. In some cases, tubular pits invaginated secondarily from the fissure and pit were observed. In some, a dental calculus can be observed in the fissure and pit. By the observation of the inner structure of the dental calculus, mineralization occurred around and within the bacteria and in the interbacterial matrix composing the dental caluculus. Bacteria of the same degree of calcification appear in the microcolonies. PMID- 1607823 TI - [Study on cell proliferation of oral malignant tumor with transferrin receptor]. AB - Transferrin receptor (TfR) is found in the vigorous proliferating cells. The author performed an immunohistochemical study on the TfR expression in the oral tissues and a flow cytometric analysis of TfR in the Hela cells with and without an anticancer drug (CDDP). Immunohistochemically a strong reaction of the TfR was clearly found in the basal and parabasal layers of the normal epithelium and malignant tumors but rarely found in the benign tumors. In the well differentiated carcinomas, the degree of staining was not so high as compared with the poorly differentiated ones. The fluorescence intensity of the cells in the CDDP 0.5 micrograms/ml group was not different from that in the control group. The intensity in the 1.0 micrograms/ml, 24 hr group was almost the same as that in the control group, but in the 1.0 micrograms/ml, 48 hr group a decrease of 18% and in the 72 hr group a decrease of 23% were observed. The intensity in the 2.0 micrograms/ml, 24 hr group decreased by 10%, and in the 2.0 micrograms/ml, 48 and 72 hr groups, it decreased more radically but a number of dead cells was recognized. From these results, the quantity of the TfR seemed to be parallel to the degree of the proliferative ability of the cancer cells. Examination with TfR can be helpful for the diagnosis and the determination of the therapeutic effect on oral cancer. PMID- 1607824 TI - [Presence of thymus-dependent CD4+8+ intestinal intraepithelial lymphocytes and their characteristics in mice]. AB - The purpose of this study was the investigation of the T cell subsets in the gut associated lymphoid tissues. CD4+8+ T cells were found to appear temporarily in Peyer's patches of mice at 2 to 3 weeks after birth. They disappeared within a short period of time from Peyer's patches, but constantly populated in the intestinal intraepithelial lymphocytes (iIEL). Three to 10% of iIEL were CD4+8+ in the specific pathogen-free (SPF) condition throughout life. They are mature T cells with a high density of CD3 and TcR alpha beta and found to respond to immobilized anti-CD3 antibody. The appearance of CD4+8+ T cells in iIEL was found to be dependent on the thymic selection, since they were absent in the athymic nu/nu mice, and the V beta gene usage was dictated by the pattern of thymic selection. CD4+8+ T cells were not found in the germ-free mice but increased in the SPF old mice. These results indicate that the iIEL contain a unique subset of thymus-derived mature CD4+8+ T cells. These cells may repopulate after the thymic selection in the intestine and increase in response to the intestinal microenvironments. PMID- 1607825 TI - [High accuracy measuring device for dental cast--using device with flat laser beam]. AB - A new system has been developed for measuring the surface morphology of the occlusal material. The main characteristic of the system is utilizing a flat laser beam to produce high accuracy measuring and to enable measuring 200 points at the same time on a line of 30 mm in length. It takes 8 to 10 minutes to digitize the whole morphology of a dental cast. The system has a central processing unit that assembles a series of digitized points into a data file of the dental morphology. It is also able to recognize the graphical image of the numerically reconstructed morphology on the CRT. Application of this measuring system enables the approach to the qualitative and quantitative evaluation of the spatial relationship between the opposing teeth at near the occlusal contact. PMID- 1607826 TI - [Studies on marginal castability of cast crown]. AB - The castability of the crown margins was studied. The smoothness and quantitative measurement of the margins were compared with the original wax patterns and their casted products. Wax patterns of the plate and crown forms were fabricated with sharp, straight and even margins. Margin angles of the wax patterns were prepared at both 20 and 40 degrees for the plate type and 20 degrees for the crown type samples. Each wax pattern was casted with Type IV gold alloy and gold-silver palladium alloy. The casted margins were evaluated by comparing them with their original wax patterns. The results were as follows: 1. Compared to the current procedure, more precise evaluation of the marginal castability is now possible with this new method. 2. The shortness of the margins was observed in all of the casted samples. Casted samples with 20-degree margins resulted in twice as much deficiency as compared to those with 40-degree margins. 3. The smoothness and evenness of the margins were inferior in all of the casted samples when compared to their original wax patterns. 4. The margin thickness was between 50 and 70 microns when the wax patterns with sharp margins were casted. 5. A certain thickness is required at the margins of the wax patterns in order to achieve precise casted margins. In this study, it was found to be 79.1 microns. PMID- 1607827 TI - [Mechanical property and adaptability of super-plastic titanium alloy denture base]. AB - The purpose of this study is to investigate the mechanical property and the adaptability of the upper complete denture bases made by superplastic forming of Ti-6A1-4V alloy plates which have various thicknesses. The strength of the denture base made by superplastic forming using the 0.55 mm thickness plate was lower than that of the base made by Co-Cr alloy casting in the standard form when loaded on the hard metal board. But by increasing the thickness by partial or full diffusion bonding of two Ti-6A1-4V alloy plates, the denture base became stronger than the Co-Cr alloy base. With resin occlusion rims, all the denture bases were reinforced. Moreover, when loaded on the mastermodel covered with rubber in the residual ridge and palate area, the difference of the strain between the thin and the thick bases became small. However, the strain of the thin base increased particularly when the base had a contact with the mastermodel on a small area in the palate. The superplastic forming denture bases revealed a high adaptability with the space less than 0.13 mm on the average between the base and the mastermodel. And increasing the thickness of the base prevented the worsening of the adaptability after curing resin for the denture. PMID- 1607828 TI - [Study on screening of high-caries-risk children by using number of DMFT at 6 years of age]. AB - This study was carried out to contrive a screening level and select high-caries risk school-children by using the number of dmft in the deciduous canines and molars at 6 years of age. The screening level was established at 9 dmft by analyzing the longitudinal caries data from 119 primary schoolchildren in Tomisato, Chiba Prefecture. Thirty-three percent of the high-caries-risk children, selected by the application of this screening level to the other three primary schools, were predicted that the mean number of DMFT would be 6 or more at 11 years of age. However, this screening level was not available for the two schools which had been adopting a fluoride mouth rinsing program because of their low caries experience at 11 years of age. PMID- 1607829 TI - [Polymorphonuclear leukocyte-mediated effects on human oral keratinocytes by periodontopathic bacterial extracts]. AB - In order to investigate the polymorphonuclear leukocyte-mediated oral keratinocyte injury, the author established a method to culture keratinocytes (SCC9 and gingival keratinocytes) and subjected to the cell detachment assay by polymorphonuclear leukocytes and/or bacterial ultrasonic extracts from Actinobacillus actinomycetemcomitans Y4, Bacteroides forsythus OMZ 408, Fusobacterium nucleatum ATCC 10953, Capnocytophaga sputigena 4 and Eikenella corrodens 1073. The bacterial extracts alone caused no cell disruption of the keratinocyte monolayers. Polymorphonuclear leukocyte alone caused only a minimal cell detachment. On the contrary, when the bacterial extracts were added to the co-culture of keratinocytes and polymorphonuclear leukocytes, cell detachment of keratinocytes was observed except for the bacterial extract from Eikenella corrodens 1073. The effect of Actinobacillus actinomycetemcomitans Y4 was the strongest. This effect was heat labile and not inhibited by polymyxin B. Cell detachment was inhibited by alpha 1-antitrypsin but not by catalase and superoxide dismutase. No keratinocyte lysis was observed in terms of 51Cr release. Hydrogen peroxide and leukocyte elastase also caused keratinocyte detachment. These results indicate that polymorphonuclear leukocyte can cause non lytic cell detachment of the gingival keratinocytes when encountering some bacteria, which may lead to the increase of the permeability of the keratinocyte layers. PMID- 1607830 TI - [Local compressibility of denture foundation--evaluation of denture foundation in relation to impression pressure]. AB - The viscoelastic character of the denture foundation is different in each individual or site. The character of the mucosa and the appropriate impression procedure should be examined. However, few investigations concerning the relation between the compressibility of the denture foundation and the impression pressure have been reported. The purpose of this study was to discuss the objective evaluation of the denture foundation in relation to the impression pressure. In this report, the local compressibility of the denture foundation of 20 upper edentulous patients was measured with the 20 MHz B-Mode ultrasonic diagnostic equipment. The Compressible Index was defined to analyze the compressibility of the denture foundation quantitatively as against the impression pressure. The main results were as follows: 1. The compressible amount of the denture foundation against 100 gw/cm2 pressurization was an average of 0.32-0.61 mm. 2. The compressible rate of the denture foundation against 100 gw/cm2 pressurization was an average of 13.5-20.7%. 3. The Compressible Index was confirmed to represent the compressibility of the denture foundation accurately as against the impression pressure. 4. It was suggested that the Compressible Index was useful for the clinical simple evaluation of the denture foundation. PMID- 1607831 TI - Re: Patient advance directives. PMID- 1607832 TI - Re: Retraction in November, 1991, issue. PMID- 1607833 TI - Re: Breast implants. PMID- 1607835 TI - Of our color. PMID- 1607834 TI - Re: April issue. PMID- 1607836 TI - Sports medicine. PMID- 1607837 TI - Sports medicine. Introducing this issue. PMID- 1607838 TI - The preparticipation screening evaluation. PMID- 1607839 TI - The ageless athlete. PMID- 1607840 TI - The female as a sports participant. AB - The physician caring for the female athlete must be aware of the anatomic and physiologic differences between the sexes. Not only do these differences impact on sport participation, but they can also affect the types of injuries seen in women athletes. However, just as in male athletes, adequate conditioning improves performance and reduces the risk of injury, and thus, is an essential component of sport participation. PMID- 1607841 TI - Shoulder function and dysfunction in the baseball pitcher. PMID- 1607842 TI - Ligamentous injuries to the lateral aspect of the ankle: the ankle sprain. AB - Good protective devices are available which will prevent or reduce the severity of ankle sprains. If an injury to the lateral ligaments of the ankle--an ankle sprain--is sustained, functional treatment with early tape support, followed by a plastic support device will return the vast majority of the injured athletes to competition rapidly and with a stable ankle. In a few cases, surgical repair is the most appropriate treatment to return the individual to his chosen endeavor with a stable ankle. PMID- 1607843 TI - Anterolateral impingement of the ankle. AB - Anterolateral impingement syndrome of the ankle is caused by entrapment of the hypertrophic soft tissue in the lateral gutter. The impingement process begins when an inversion sprain tears the anterior talofibular, and/or the calcaneofibular ligament. The ligamentous injury is not severe enough to cause chronic instability; however, inadequate immobilization and rehabilitation may lead to chronic inflammation in the ligament, resulting in formation of scar tissue. This tissue then becomes trapped between the talus and the lateral malleolus, causing irritation, pain, and further synovitis. The end result is chronic lateral ankle pain. Initial treatment involves physical therapy modalities and nonsteroidal anti-inflammatory medications. Those patients refractory to conservative treatment require arthroscopic debridement. A recent study has shown that arthroscopic debridement is successful in relieving pain and disability in high percentages of patients. Most patients were able to return to their previous levels of work and sports. Successful treatment of anterolateral impingement requires an accurate diagnosis with a clinical evaluation that excludes other causes of chronic ankle pain. PMID- 1607844 TI - Acute hemarthrosis of the knee. AB - Rapid swelling of the knee following a blow or twisting injury is considered a significant injury. The history of trauma coupled with a thorough examination should provide an accurate diagnosis in most patients. Although it should not be performed routinely, aspiration of the fluid can be done to aid in making a diagnosis and to alleviate pain. Splinting and re-evaluation are recommended as the initial treatment of an acute hemarthrosis. Ancillary testing that includes x ray films and MRIs is beneficial. Although arthroscopic evaluation of the knee is not needed in every patient with an acute hemarthrosis, a high percentage of these patients eventually undergo arthroscopy to complete the diagnosis or as a means of early surgical intervention. The decision to surgically repair an injured structure depends on the patient's age, activity level, amount of instability, and associated lesions. Routine arthroscopy is indicated as a means to determine the correct treatment and not merely for diagnosis. With knowledge of the common causes of hemarthrosis and understanding of the knee examination, a trained examiner can make an accurate diagnosis 80% to 90% of the time and prescribe the appropriate treatment. PMID- 1607845 TI - The effects of heat on the athlete. PMID- 1607847 TI - Spine injury in sports. PMID- 1607846 TI - Cardiac arrhythmias in presidents and other athletes. AB - We presented examples of both supraventricular and ventricular rhythm disorders which can occur in athletic individuals, even presidents. The vast majority of rhythm problems we deal with in athletes are fortunately benign, entities such as frequent atrial ectopic beats or VPBs. In each patient encountered, we ask ourselves the five questions noted in the discussion pertaining to symptomatology, anatomic source of the arrhythmia, presence or absence of underlying cardiac disease, and precipitating factors. The most common more sustained SVTs we see are AVNRT and atrial fibrillation. Atrial flutter is less common. These are more of a nuisance to patients rather than a threat to their lives, although rarely cerebral embolic events can occur. Therapy includes avoidance of precipitating factors and, when necessary, a sequential trial of available drugs, carefully documenting the response and watching closely for any pro-arrhythmic events. We infrequently see NSVT in athletes, even triplets of VPBs on exercise testing, and rarely see instances of sustained VT. The latter merits a careful search for underlying cardiac disease and usually electrophysiology-guided drug therapy. New techniques such as radiofrequency ablation of the dysrhythmic focus may obviate the need for chronic drug therapy in selected cases. PMID- 1607848 TI - From the Georgia Medical Care Foundation: "premature discharge" as a peer review concept. PMID- 1607849 TI - Maxillofacial prosthodontics: an aid to the oncology patient. PMID- 1607850 TI - Controlling the spread of AIDS. Confidential information. PMID- 1607851 TI - Effects of anions on the G protein-mediated activation of the muscarinic K+ channel in the cardiac atrial cell membrane. Intracellular chloride inhibition of the GTPase activity of GK. AB - The effects of various intracellular anions on the G protein (GK)-mediated activation of the muscarinic K+ (KACh) channel were examined in single atrial myocytes isolated from guinea pig hearts. The patch clamp technique was used in the inside-out patch configuration. With acetylcholine (ACh, 0.5 microM) in the pipette, 1 microM GTP caused different magnitudes of KACh channel activation in internal solutions containing different anions. The order of potency of anions to induce the KACh channel activity at 0.5 microM ACh and 1 microM GTP was Cl- greater than or equal to Br- greater than 1-. In the SO4(2-) or aspartic acid internal solution, no channel openings were induced by 1 microM GTP with 0.5 microM ACh. In both the Cl- and SO4(2-) internal solutions (with 0.5 microM ACh) the relationship between the concentration of GTP and the channel activity was fit by the Hill equation with a Hill coefficient of approximately 3-4. However, the concentration of GTP at the half-maximal activation (Kd) was 0.2 microM in the Cl- and 10 microM in the SO4(2-) solution. On the other hand, the quasi steady-state relationship between the concentration of guanosine-5'-o-(3 thiotriphosphate) and the channel activity did not differ significantly between the Cl- and SO4(2-) solutions; i.e., the Hill coefficient was approximately 3-4 and the Kd was approximately 0.06-0.08 microM in both solutions. The decay of channel activity after washout of GTP in the Cl- solution was much slower than that in the SO4(2-) solution. These results suggest that intracellular Cl- does not affect the turn-on reaction but slows the turn-off reaction of GK, resulting in higher sensitivity of the KACh channel for GTP. In the Cl- solution, even in the absence of agonists, GTP (greater than 1 microM) or ATP (greater than 1 mM) alone caused activation of the KACh channel, while neither occurred in the SO4(2 ) solution. These observations suggest that the activation of the KACh channel by the basal turn-on reaction of GK or by phosphate transfer to GK by nucleoside diphosphate-kinase may depend at least partly on the intracellular concentration of Cl-. PMID- 1607853 TI - Force and stiffness in glycerinated rabbit psoas fibers. Effects of calcium and elevated phosphate. AB - Force (F) and stiffness (K) were measured in glycerinated psoas fibers at various calcium levels with 0, 10, 20, and 30 mM orthophosphate (Pi) added to the bathing solutions. The concentrations of bathing solution constituents were as follows: 110 mM potassium, 40 mM sodium, 4 mM MgATP, 10 mM total EGTA, and variable amounts of MOPS (pH buffer). The pH was 7.0, the ionic strength was 200 mM, and the temperature was 10 degrees C. Calcium levels were established by adding various amounts of CaCl2. All solutions contained 4% Dextran T-500. Fiber K was measured by imposing sinusoidal length changes (0.03-0.1%) at 1 kHz and by applying rapid steps in length and measuring the resulting F changes. At all [Pi] tested, K was more sensitive to calcium than F. Elevating bathing solution [Pi] caused a decrease in the calcium sensitivity of both F and K, while the slopes of F-calcium and K-calcium relations increased. In maximally activating calcium, raising [Pi] caused a continuous decrease in F over the range tested, while from very low to 10 mM Pi K remained constant. Above 10 mM Pi K declined, but to a lesser extent than did F. The results suggest that under our experimental conditions strongly attached crossbridges can exist in both force-producing and non-force-producing states, and that the relative population of these states may be calcium dependent. PMID- 1607852 TI - Internal magnesium, 2,3-diphosphoglycerate, and the regulation of the steady state volume of human red blood cells by the Na/K/2Cl cotransport system. AB - This study is concerned with the relationship between the Na/K/Cl cotransport system and the steady-state volume (MCV) of red blood cells. Cotransport rate was determined in unfractionated and density-separated red cells of different MCV from different donors to see whether cotransport differences contribute to the difference in the distribution of MCVs. Cotransport, studied in cells at their original MCVs, was determined as the bumetanide (10 microM)-sensitive 22Na efflux in the presence of ouabain (50 microM) after adjusting cellular Na (Nai) and Ki to achieve near maximal transport rates. This condition was chosen to rule out MCV-related differences in Nai and Ki that might contribute to differences in the net chemical driving force for cotransport. We found that in both unfractionated and density-separated red cells the cotransport rate was inversely correlated with MCV. MCV was correlated directly with red cell 2,3-diphosphoglycerate (DPG), whereas total red cell Mg was only slightly elevated in cells with high MCV. Thus intracellular free Mg (Mgifree) is evidently lower in red cells with high 2,3-DPG (i.e., high MCV) and vice versa. Results from flux measurements at their original MCVs, after altering Mgifree with the ionophore A23187, indicated a high Mgi sensitivity of cotransport: depletion of Mgifree inhibited and an elevation of Mgifree increased the cotransport rate. The apparent K0.5 for Mgifree was approximately 0.4 mM. Maximizing Mgifree at optimum Nai and Ki minimized the differences in cotransport rates among the different donors. It is concluded that the relative cotransport rate is regulated for cells in the steady state at their original cell volume, not by the number of copies of the cotransporter but by differences in Mgifree. The interindividual differences in Mgifree, determined primarily by differences in the 2,3-DPG content, are responsible for the differences in the relative cotransport activity that results in an inverse relationship with in vivo differences in MCV. Indirect evidence indicates that the relative cotransport rate, as indexed by Mgifree, is determined by the phosphorylated level of the cotransport system. PMID- 1607854 TI - Na(+)-dependent Cl-HCO3 exchange in the squid axon. Dependence on extracellular pH. AB - Intracellular pH (pHi) in squid giant axons recovers from acid loads by means of a Na(+)-dependent Cl-HCO3 exchanger, the actual mechanism of which might be exchange of: (i) external Na+ and HCO3- for internal Cl- and H+, (ii) Na+ plus two HCO3- for Cl-, (iii) Na+ and CO3= for Cl-, or (iv) the NaCO3- ion pair for Cl . Here we examine sensitivity of transport to changes of extracellular pH (pHo) in the range 7.1-8.6. We altered pHo in four ways, using: (i) classical "metabolic" disturbances in which we varied [HCO3-]o, [NaCO3-]o, and [CO3=]o at a fixed [CO2]o; (ii) classical "respiratory" disturbances in which we varied [CO2]o, [NaCO3-]o, and [CO3=]o at a fixed [HCO3-]o; (iii) novel mixed-type acid base disturbances in which we varied [HCO3-]o and [CO2]o at a fixed [CO3=]o and [NaCO3-]o; and (iv) a second series of novel mixed-type disturbances in which we varied [CO2]o, [CO3=]o, and [Na+]o at a fixed [HCO3-]o and [NaCO3-]o. Axons (initial pHi approximately 7.4) were internally dialyzed with a pH 6.5 solution containing 400 mM Cl- but no Na+. After pHi, measured with a glass microelectrode, had fallen to approximately 6.6, dialysis was halted. The equivalent acid extrusion rate (JH) was computed from the rate of pHi recovery (i.e., increase) in the presence of Na+ and HCO3-. When pHo was varied by method (i), which produced the greatest range of [CO3=]o and [NaCO3-]o values, JH increased with pHo in a sigmoidal fashion; the relation was fitted by a pH titration curve with a pK of approximately 7.7 and a Hill coefficient of approximately 3.0. With method (ii), which produced smaller changes in [CO3=]o and [NaCO3-]o, JH also increased with pHo, though less steeply. With method (iii), which involved changes in neither [CO3=]o nor [NaCO3-]o, JH was insensitive to pHo changes. Finally, with method (iv), which involved changes in neither [HCO3-] nor [NaCO3-]o, but reciprocal changes in [CO3=]o and [Na+]o, JH also was insensitive to pHo changes. We found that decreasing pHo from 8.6 to 7.1 caused the apparent Km for external HCO3- ([Na+]o = 425 mM) to increase from 1.0 to 26.7 mM, whereas Jmax was relatively stable. Decreasing pHo from 8.6 to 7.4 caused the apparent Km values for external Na+ ([HCO3-]o = 48 mM) to increase from 8.6 to 81 mM, whereas Jmax was relatively stable.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1607855 TI - Transcription of a recombinant influenza virus RNA in cells that can express the influenza virus RNA polymerase and nucleoprotein genes. AB - A new transfection system for influenza virus was developed using the clone 76 cell line, in which the viral RNA polymerase and nucleoprotein (NP) genes can be expressed in response to dexamethasone. Ribonucleoprotein (RNP) complexes were reconstituted by expressing proteins from a chimeric NS-chloramphenicol acetyltransferase (CAT) RNA consisting of the full-length negative-strand RNA of the CAT gene positioned between the 5'- and 3'-terminal sequences of influenza virus RNA segment 8, and purifying NP from an NP gene-expressing Escherichia coli strain. When the reconstituted RNP was transfected into clone 76 cells, CAT was produced only when the synthesis of the three RNA polymerase subunits and NP was induced by treatment with dexamethasone. PMID- 1607856 TI - Origin and evolutionary characteristics of antigenic reassortant influenza A (H1N2) viruses isolated from man in China. AB - During the 1988/1989 influenza season, five antigenic reassortant influenza A (H1N2) viruses not previously isolated from man were isolated in Hebei province, People's Republic of China. All isolates contained haemagglutinins (HAs) and neuraminidases (NAs) which were antigenically similar to those of the recent Russian (H1N1) and Hong Kong influenza A (H3N2) viruses, respectively. The results of antigenic and nucleotide sequence analyses revealed that the genes encoding the polymerase, nucleoprotein, NA, matrix and non-structural proteins of the reassortant A/Hebei/24/89 (H1N2) virus were derived from the H3N2 parent virus, whereas its HA gene was from the H1N1 parent virus. The nucleotide sequences of the HA (encoding the HA1 subunit) and NA genes of the reassortant viruses were also determined. Phylogenetic trees constructed from these data by the neighbour-joining method revealed that the HA gene of the reassortant virus was closely related to those of recent human H1N1 viruses, whereas the NA gene was related to a recent human Hong Kong (H3N2) virus lineage. PMID- 1607857 TI - Influenza virus pyrogenicity: central role of structural orientation of virion components and involvement of viral lipid and glycoproteins. AB - Ultraviolet light-inactivated, non-infectious influenza virus is pyrogenic; virion components are probably responsible for this pyrogenicity. To try to identify the pyrogenic component, influenza virions were disrupted with either bromelain or sodium deoxycholate (DOC). Treatment of infectious virions with bromelain, under conditions that removed the surface glycoproteins (spikes), destroyed their pyrogenicity. The supernatant, containing non-aggregated and modified glycoproteins, was also non-pyrogenic. Disruption of virions with DOC considerably reduced pyrogenicity; however, some was retained by the sub-viral cores. Viral nucleoprotein and matrix protein, purified from the supernatant, were non-pyrogenic. Aggregated stellate clusters of surface glycoproteins separated on sucrose gradients were pyrogenic in half of numerous tests performed with different batches of material. Treatment of virus with ether resulted in complete loss of pyrogenicity. Liposomes made from extracted viral lipid were non pyrogenic. In contrast, virosomes made from the viral lipid and the aggregated stellate clusters of surface glycoproteins were pyrogenic. Hence, optimum pyrogenicity depends upon the integrity of the virus particle, but haemagglutinin and/or neuraminidase appear essential, and lipid may be involved. PMID- 1607858 TI - Sequence and in vitro expression of the M2 gene of turkey rhinotracheitis pneumovirus. AB - Negative-stranded virion RNA and oligonucleotide primers complementary to fusion (F) protein gene sequences were used to generate cDNA clones, revealing that the gene 5'-proximal to the F protein corresponded to the M2 (22K) gene, as in respiratory syncytial (RS) virus. The transcription start signal, GGGACAAGU, was identical to that of the F and matrix (M) proteins of turkey rhinotracheitis virus (TRTV). There were two sequences with the potential to function as transcription termination/poly(A) signals, located at nucleotides 751 to 762 and 777 to 787; 15 clones derived from mRNA indicated that the first of these sequences formed the major signal. Part of the next downstream (5') gene was sequenced; unlike mammalian pneumoviruses the TRTV M2 gene did not overlap the beginning of the 5'-proximal gene. Northern blotting indicated that infected Vero cells contained less M2 mRNA than F mRNA and that about half of the M2 mRNA was present as a F-M2 dicistronic mRNA. The M2 gene contained two overlapping open reading frames (ORFs 1 and 2), as with RS virus. ORF 1 comprised 558 nucleotides with the coding potential for a 186 amino acid polypeptide, M(r) 20959, eight or nine residues shorter than for human RS virus strains. The overall amino acid identity was 40%, the N-terminal one-third of the proteins sharing 62% of residues, the remainder 29%. A hydropathy plot of the TRTV M2 protein had close similarity to that of the M2 or RS virus. The protein was predicted to have a basic character with no N-terminal signal sequence or other major highly hydrophobic sequences. In vitro translation of a transcript comprising both ORFs 1 and 2 produced a single product of apparent M(r) 23000, corresponding to the M2 product of ORF 1. Site-directed mutagenesis confirmed that this product was derived from ORF 1 and that frameshifting was not involved. The second ORF was expressed only from a transcript which lacked the AUG codons of ORF 1 and, although occupying a similar position to that in the RS virus M2 gene, had virtually no amino acid identity in its 73 residue length and was approximately 25% shorter than the corresponding RS virus ORF 2. The hydropathy plot of the potential products of the second ORFs of TRTV and RS virus showed little resemblance. Taken together these results suggest that ORF 2 is unlikely to be expressed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1607859 TI - Coxsackievirus B4 infection of the mouse pancreas: the role of natural killer cells in the control of virus replication and resistance to infection. AB - The role of natural killer (NK) cells in the early immune response to a pancreatropic isolate of coxsackievirus B4 (CVB4) was investigated in a murine model of pancreatitis. Endogenous (background) NK cell activity in fresh spleen effector cells from eight mouse strains was compared with virus-augmented NK cell activity 4 days post-infection (p.i.). A significant virus-induced increase (P less than or equal to 0.003) in NK cell activity was seen in seven of eight infected mouse strains, when virus titres in the pancreas were beginning to fall. Lesions in the exocrine pancreas were least extensive in the three strains with the highest endogenous NK cell activity. In C3H/HeJ mice that had been depleted of NK cells prior to infection with a low virus concentration, resistance to infection of the pancreas was completely abolished; myocarditis was also observed in one of these animals. Thus, NK cells may limit virus replication in the pancreas and play a role in resistance in C3H/HeJ mice. Virus-specific neutralizing antibody was not detected in the serum until 5 to 6 days p.i. in most strains and did not appear to influence pancreatic virus titres. It may be significant that CVB4 infection did not induce the expression of major histocompatibility complex (MHC) class I molecules on target acinar cells. With certain tumour cells, an inverse relationship between MHC class I expression and susceptibility to NK cell-mediated lysis is well documented. PMID- 1607861 TI - Comparisons of the genomic sequences of erysimum latent virus and other tymoviruses: a search for the molecular basis of their host specificities. AB - The nucleotide sequence of the genome of erysimum latent tymovirus (ELV) has been determined. It closely resembles those of the other four sequenced tymoviral genomes in its gene organization and composition, but is the smallest (6034 nucleotides) and most distinct of them. Furthermore the 78 non-coding nucleotides at the 3' terminus of the ELV genome are unable to form a complete tRNA-like structure like that reported for other tymoviruses. Comparisons of the five tymovirus genomes and their encoded proteins indicate that they have probably evolved from the progenitor tymovirus by independent progressive mutational change without genetic recombination. Comparisons of the sequences of the two non virion proteins of five tymoviruses, and virion proteins of 17 tymoviruses, revealed no specific similarities between those of ELV and turnip yellow mosaic virus that could explain why their host ranges and symptoms are so similar, yet differ, in this respect, from ononis yellow mosaic, kennedya yellow mosaic and eggplant mosaic tymoviruses. PMID- 1607860 TI - Coxsackievirus B4 infection of the mouse pancreas: acute and persistent infection. AB - The course of infection of a pancreas-adapted isolate of coxsackievirus B4 was followed over a 10 month period in a murine model. Following intraperitoneal inoculation a typical acute infection was seen in nine of 10 inbred mouse strains. Virus rapidly infected the exocrine pancreas, titres peaking 3 to 4 days post-infection (p.i.). Lesions were almost exclusively confined to pancreatic acinar cells and varied in severity among the inbred strains. Virus shed into the blood-stream was not cell-associated. Evidence of persistent infection was found in nine mouse strains and infective virus was recovered from the pancreas of seven strains for up to 10 months p.i. Approximately 28% of pancreases examined beyond the acute phase showed focal inflammation and 22% showed focal necrosis (cell death). Virus was occasionally recovered from other organs (heart, liver and spleen), but lesions were rarely seen. Virus-specific antigen was localized to small groups of pancreatic acinar cells using an indirect immunogold silver staining technique. These observations suggested that the virus persists in pancreatic tissues because it seems unlikely that virus disseminated from distant sites would cause such localized infection. In three of these strains, the course of infection may have been influenced by superinfection with mouse hepatitis virus. PMID- 1607862 TI - The mode of cauliflower mosaic virus propagation in the plant allows rapid amplification of viable mutant strains. AB - We inoculated the leaves of turnip plants (Brassica campestris spp. rapa cv. Just Right) with two cauliflower mosaic viruses (CaMVs) with different small mutations in a dispensable region of the viral genome, and followed the spread of the virus infection through the plant. Surprisingly, analysis of viral DNA in single primary chlorotic lesions revealed the presence of both mutants. In contrast, the secondary chlorotic lesions and systemically infected leaves contained virus molecules of either one or the other type only. Infection of plants with different ratios of the two reporter viruses showed that this ratio is not conserved during systemic virus spread. Infection with CaMV DNA in the form of heteroduplexes containing a single mismatched base pair, in which each strand carried a distinct diagnostic marker, provided us with evidence that the mismatch was subjected to a repair process in the host plant. PMID- 1607863 TI - Rice hoja blanca virus genome characterization and expression in vitro. AB - No information exists on the organization and mechanisms of expression of the genome of rice hoja blanca virus (RHBV), a member of the tenuivirus group, but here we describe the first steps in its characterization. RHBV contains four ssRNA and three dsRNA species, the sizes of which were estimated by native and denaturing gel electrophoresis. Hybridization analyses using 32P-labelled riboprobes of viral and viral complementary polarities showed that unequal amounts of the two polarities of at least the smallest RNA are present in the virion, and indicated that the dsRNA species contain the same information as the ssRNA species of corresponding size. Total RHBV RNA directs the synthesis of two major proteins of 23K and 21K in vitro. RNA3 directs the synthesis of a 23K protein designated NS3, and RNA4 of a 21K protein designated NS4. The NS4 protein corresponds to the non-structural protein that accumulates in RHBV-infected rice tissue. The nuclecocapsid protein is not translated from either total RHBV RNA or any individual RHBV RNA in vitro. PMID- 1607864 TI - Relationships among the viroids derived from grapevines. AB - There have been numerous reports of grapevine viroids, describing physical and biological properties suggestive of similar or identical molecular forms. With consideration of these properties and the application of random-primed and specific cDNA probes, four major groups of grapevine viroids have been defined. Designations which can be used to describe distinct viroids within the four groups include (i) CEVd-g, a grapevine isolate of citrus exocortis viroid, (ii) GVd-c, a grapevine viroid recovered from cucumber, and AGVd, Australian grapevine viroid, (iii) GYSVd-1 and GYSVd-2, two viroids inducing yellow speckle disease and (iv) HSVd-g, a grapevine isolate of hop stunt viroid. PMID- 1607865 TI - Analysis of polyhedra morphology mutants of Autographa californica nuclear polyhedrosis virus: molecular and ultrastructural features. AB - Two new mutants of Autographa californica multiple nuclear polyhedrosis virus affected in the morphogenesis of their polyhedra, designated M276 and M934, were investigated. Marker transfer experiments demonstrated that the observed phenotype was due exclusively to alterations in the polyhedrin gene. M276 contained a 229 base insertion near the carboxyl terminus coding region which resulted in synthesis of a truncated protein; M934 had a point mutation substituting phenylalanine for leucine at amino acid 183. Both mutations occurred in highly conserved regions of the protein and prevented the occlusion of virus particles, but did not affect targeting for the intranuclear ring zone. M276 was distinct in that it had prominent cytosolic condensations of polyhedrin, although these were probably due to a decreased protein solubility. M934 polyhedrin condensations associated prematurely with calyx material such that it became incorporated into the condensation rather than at the surface. Results confirm that occlusion size and shape are features inherent to the polyhedrin protein, and suggest that polyhedrin conformation may help regulate the occlusion process. PMID- 1607866 TI - Dissimilar expression of Autographa californica multiple nucleocapsid nuclear polyhedrosis virus polyhedrin and p10 genes. AB - The temporal expression of the Autographa californica multiple nucleocapsid nuclear polyhedrosis virus polyhedrin and p10 genes in Spodoptera frugiperda cells was studied using virus recombinants in which either gene was replaced by the juvenile hormone esterase (JHE) gene of Heliothis virescens. The JHE served as a highly specific and sensitive reporter for gene expression. Activation of the p10 gene followed a pattern different to that of polyhedrin. The p10 gene was activated a few hours earlier than the polyhedrin gene, but its expression reached a lower maximum level. Northern blot analysis complemented and confirmed the results obtained from the JHE assays. Co-infection of sense recombinants and those containing an antisense copy of the JHE gene in place of the polyhedrin or p10 gene resulted in reduced levels of JHE gene expression. These experiments independently supported the hypothesis that the p10 gene promoter is more active at earlier times post-infection than that of the polyhedrin gene. The results also highlight the potential of the antisense strategy as an experimental approach for the study of baculovirus gene regulation and possibly insect metabolism. PMID- 1607867 TI - Restriction endonuclease analysis and mapping of the genomes of granulosis viruses isolated from Xestia c-nigrum and five other noctuid species. AB - Restriction endonuclease analysis was performed on the genomic DNA of granulosis viruses isolated from noctuid species of six genera: Xestia c-nigrum, Autographa gamma, Hydraecia amurensis, Celaena leucostigma, Aletia pallens and Pseudaletia separata. All of the isolates gave very similar restriction endonuclease profiles with only minor variations. An isolate obtained from X. c-nigrum was chosen as the reference genotype, and a genomic library was constructed for this isolate using plasmid vectors. The genome was mapped using EcoRI, BamHI and BglII, and Southern hybridization; the size of the genome was estimated to be 179 kbp. Hybridization of labelled clones to fragments of other isolates revealed that genotypic variation among isolates resulted from changes in restriction sites, and from deletion or insertion of DNA. Comparative restriction mapping revealed that all of the isolates were variants of one virus, even though they originated from different host species. PMID- 1607868 TI - Nucleotide sequence of the polyhedron envelope protein gene region of the Lymantria dispar nuclear polyhedrosis virus. AB - A 6.4 kb region from the Lymantria dispar multicapsid nuclear polyhedrosis virus (LdMNPV) genome was sequenced and found to contain open reading frames (ORFs) homologous to the polyhedron envelope (PE) protein coding sequence, and the C terminal half of ORF 1, which is a gene located upstream of the PE protein gene in other baculoviruses. The proteins predicted from the LdMNPV genes encoding the PE protein, and ORF 1 demonstrated 27 and 34% amino acid sequence identity, respectively, with the corresponding genes in the Autographa californica multicapsid nuclear polyhedrosis virus. PMID- 1607869 TI - Nucleotide sequence of the p39-capsid gene region of the Lymantria dispar nuclear polyhedrosis virus. AB - A 1.85 kb region, containing an open reading frame (ORF) homologous to the baculovirus p39-capsid gene, was sequenced from the Lymantria dispar multicapsid nuclear polyhedrosis virus (LdMNPV) genome. Analysis of the p39-capsid gene demonstrated that it was 39% and 47% identical in amino acid sequence with the homologous genes in the Autographa californica and Orgyia pseudotsugata MNPVs, respectively. Two late promoter elements located upstream of the p39 gene in the LdMNPV genome are conserved with two other baculoviruses, whereas an ORF located downstream is not conserved. PMID- 1607870 TI - Genetic engineering of a Lymantria dispar nuclear polyhedrosis virus for expression of foreign genes. AB - A bacterial lacZ gene was inserted into an isolate of the Lymantria dispar nuclear polyhedrosis virus (LdMNPV). The transfer vector was constructed by site directed mutagenesis of the translation start site of the LdMNPV polyhedrin gene, within the BglII E fragment of the viral genome. A multiple cloning sequence was inserted at this start site and used for the insertion of the lacZ gene into the transfer plasmid. Liposome transfection was used to cotransfect L. dispar tissue culture cells with viral DNA and the transfer plasmid. Recombinant LdMNPV isolates were purified by isolation of plaques producing beta-galactosidase but not polyhedra. Restriction enzyme fragment profiles were used to determine the site of the lacZ gene insertion, and DNA sequencing of the 5' and 3' ends of the lacZ gene insert and the adjoining polyhedrin promoter and coding regions was performed to identify its precise location. Expression of the lacZ gene was examined by studying virus-induced protein using [35S]methionine pulse-labelling, SDS-PAGE fractionation and autoradiography. Expression of beta-galactosidase was examined in tissue culture cells using colorimetric assays. The maximum rate of beta-galactosidase production was approximately 50 international units (IU)/10(6) tissue culture cells/day between 3 and 4 days post-infection (p.i), and the peak total expression was 158 IU/10(6) cells 5 days p.i. beta-Galactosidase activity was first detected 48 h p.i. in haemolymph samples from fourth instar L. dispar larvae injected with 10(6) p.f.u. of virus. The peak beta-galactosidase activity in larval haemolymph samples was 1931 IU/ml of haemolymph at 11 days p.i., just prior to death. PMID- 1607871 TI - Hepatitis B virus polymerase gene: expression of the long open reading frame using the baculovirus expression system. AB - A recombinant baculovirus was constructed containing a copy of the hepatitis B virus (HBV) genome which was inserted to produce an in-frame fusion of the precore (pre-C) coding region with the first 11 amino acids of the polyhedrin gene. The recombinant baculovirus expressed the 25K pre-C protein and two novel proteins, of approximately 93K and 72K. Both the 93K and 72K proteins are recognized by an anti-polymerase monoclonal antibody. Northern blot analysis of the mRNA produced during infection of Spodoptera frugiperda cells by the HBV recombinant baculovirus detected only one HBV mRNA species, suggesting that the three HBV-specific proteins expressed are translated from the same mRNA. No larger fusion proteins cross-reacting with either anti-core or polymerase antibodies were detected. These findings suggest that the two proteins encoded within the HBV polymerase gene are not produced via a core-polymerase fusion intermediate but by internal binding of ribosomes. These results are the first clear demonstration of efficient expression of two bona fide unprocessed polymerase proteins in a 1:1 ratio from an unspliced pre-C mRNA-like transcript. With the successful expression of the polymerase gene in insect cells it is now possible to produce large amounts of these proteins, allowing a more detailed structural and functional analysis of these proteins. PMID- 1607872 TI - Analysis of human immunodeficiency virus type 1 LTR-LTR junctions in peripheral blood mononuclear cells of infected individuals. AB - Circularized DNA species containing two long terminal repeat circle junctions were analysed in peripheral blood mononuclear cells of human immunodeficiency virus type 1 (HIV-1)-infected individuals. The circle junction fragments found could be classified into four groups: fragments containing a normal circle junction, fragments with deletions at the circle junction, fragments containing the primer binding site inserted at the circle junction, and fragments containing insertions at the circle junction derived from other regions of the HIV-1 genome. PMID- 1607873 TI - Non-permissiveness of synovial membrane cells to human parvovirus B19 in vitro. AB - The ability of cultured human synovial cells derived from synovial membrane and cartilage to support the replication of human parvovirus B19 was assessed. No viral DNA synthesis nor viral antigens were detected suggesting that B19 virus is not capable of replicating in synovial cells. The significance of this finding in relationship to the pathogenesis of parvovirus arthritis is discussed. PMID- 1607874 TI - A measles virus isolate from a child with Kawasaki disease: sequence comparison with contemporaneous isolates from 'classical' cases. AB - We examined the relationship between a measles virus isolate from a child with Kawasaki disease and two contemporaneous wild-type isolates from children with 'classical' measles and the Schwarz vaccine strain. Sequence analysis of 3118 bp from the nucleoprotein, matrix, fusion and haemagglutinin genes of each virus revealed that the isolate from the child with Kawasaki disease was not related to measles vaccine strains and did not contain any of the marked abnormalities previously found in subacute sclerosing panencephalitis isolates, but was more akin to wild-type isolates currently circulating in the U.K. A comparison of our sequences with those obtained from earlier wild-type U.K. isolates suggests significant evolution of measles virus in the U.K. over the last decade. PMID- 1607875 TI - Conserved terminal nucleotide sequences in the genome of rice black streaked dwarf virus. AB - The terminal regions of the dsRNA genome segments of rice black streaked dwarf virus (RBSDV) were sequenced. The individual dsRNAs, which were 32P-labelled at their 3' termini by incubation with [32P]pCp and T4RNA ligase, were separated by 5% PAGE, and the 10 dsRNA segments were sequenced by two-dimensional electrophoresis. The common 3'-terminal sequences ---GUC 3' and ---AAAAACUU 3' were found in the plus and minus strands, respectively. The strictly conserved terminal sequences (5' AAGUUUUU ... GUC 3') of the genome segments of RBSDV differ from those of the phytoreoviruses and rice ragged stunt virus. PMID- 1607876 TI - A review of recent advances in stereology for quantifying neural structure. AB - The science of stereology has undergone a revolution over the past decade with the introduction of design-based (assumption- or model-free) methods which are highly efficient and generally unbiased. No other morphometric approach currently offers these twin benefits. Stereology is ideal for extrapolating 3-D structural quantities (real volumes, surface areas, lengths and numbers) from simple counts made on 2-D slice images. The images may take various forms (e.g. physical or optical sections, MRI slices, CT scans) but they must be sampled so as to be random in orientation and/or position if valid estimates are to be made. All the recent developments in stereology are applicable to problems in neuromorphometry. This review provides an account of major developments and the state of the art, emphasizes the importance of properly randomized sampling and identifies some applications to neural structure at different levels of organization. These include the counting and sizing of synapses, neurites, cells and whole brains. PMID- 1607877 TI - The influence of muscle contractile activity versus neural factors on morphologic properties of innervated cultured human muscle. AB - In contrast to aneurally cultured human muscle, which is immature in regard to its morphologic phenotype and only rarely and weakly contracts spontaneously, innervated cultured human muscle fibres have: (1) nearly continuous, d tubocurarine-inhibitable contractions; (2) well-developed cross-striations, basal lamina, t-tubules, and postsynaptic folds of the neuromuscular junctions; (3) the majority of their nuclei peripheralized; and (4) acetylcholinesterase-positive sites present only at the neuromuscular junctions. To see whether the expression of the muscle morphologic phenotype is induced only by neural factors generated from the spinal cord explants or also by their frequent contractile activity, we paralyzed innervated cultured human muscle fibres with 2 microM tetrodotoxin for four weeks, either from the first day of muscle contractions or following four weeks of muscle contractions. In both experimental designs, by light microscopy tetrodotoxin paralysis abolished cross-striations and caused prominent internalization of muscle nuclei; however, it did not influence the intensity of acetylcholinesterase staining at the neuromuscular junctions. By electron microscopy, there was no difference between paralyzed and contracting muscle fibres in development of t-tubules, basal lamina and postsynaptic folds. Our study demonstrates that in human muscle contractile activity: (1) regulates peripheral migration of nuclei and development of cross-striations; and (2) does not influence development of the neuromuscular junction, basal lamina, and t tubules, which are mainly regulated by neural influences. This culture model may be useful for studying detailed mechanisms of human muscle fibre development and structural abnormalities in human neuromuscular diseases. PMID- 1607878 TI - Norepinephrine-containing glomus cells in the rabbit carotid body. I. Autoradiographic and morphometric study after tritiated norepinephrine uptake. AB - Rabbit carotid bodies were investigated by autoradiography at both the light and electron microscope levels following tritiated norepinephrine administration either in vivo or in vitro. Two kinds of labelled structures were found: nerve fibres (absent in sympathectomized carotid bodies) and some type I glomus cells. Desipramine (a specific norepinephrine uptake inhibitor) prevented labelling. Most of the labelled cells differed from unlabelled ones by the presence of (i) large dense-cored vesicles characterized by a large halo between the membrane and an eccentric dense core; (ii) a nucleus showing a more electron dense chromatin and a more irregular shape; and (iii) relatively abundant glycogen particles. A new weakly-labelled cells were characterized by a pyknotic nucleus and very swollen dense-cored vesicles, and were presumed to be degenerating. Dense core diameters of dense-cored vesicles were distributed according to a unimodal distribution in labelled cells as in unlabelled ones but with an extension towards both large and very small diameters in labelled cells. The mean diameter was higher in labelled cells than in unlabelled ones (127 nm versus 113 nm, P less than 0.01). The labelling intensity (as estimated by the number of silver grains per unit of cytoplasmic area) was maximum in cells having dense-cored vesicles whose mean diameter was between 130 and 170 nm, but decreased for cells with mean diameter of dense cores smaller than 130 nm, or larger than 170 nm. Thus, in the rabbit carotid body, some glomus cells differ from others by their ability to take up tritiated norepinephrine and by the presence of larger dense cored vesicles. However, this distinction is not clearcut and there are many intermediates. The observations suggest a phenomenon of evolution deriving from a unique cell type and typified by both metabolic norepinephrine uptake ability, glycogen accumulation) and morphologic changes (increase in diameter of dense cored vesicles). It seems, therefore, more appropriate to consider these results in terms of different functional states rather than different types of glomus cells. PMID- 1607879 TI - Norepinephrine-containing glomus cells in the rabbit carotid body. II. Immunocytochemical evidence of dopamine-beta-hydroxylase and norepinephrine. AB - The presence of noradrenergic glomus cells in the rabbit carotid body was investigated at the light and electron microscope levels, using dopamine-beta hydroxylase and norepinephrine immunocytochemistry as well as the chromaffin reaction. Frozen and semi-thin plastic sections showed some dopamine-beta hydroxylase immunoreactive glomus cells either isolated in the connective tissue or, more frequently, mixed with unreactive cells. At the ultrastructural level immunopositive cells differed from immunonegative ones by the larger size of most of their dense-cored vesicles. Similar observations were made after using anti norepinephrine antibodies. Immunoreactive cells to anti-dopamine-beta-hydroxylase and anti-norepinephrine antibodies were relatively few although their number varied from carotid body to carotid body. The immunolabelling intensity was very variable from cell to cell. Consecutive frozen sections processed for norepinephrine- and dopamine-immunocytochemistry showed many cell clusters containing both norepinephrine and dopamine-immunoreactive glomus cells. Some chromaffin glomus cells were clearly identifiable by the very strong electron opacity of their dense-cored vesicles; most of these vesicles were characterized by their large size, as the dense-cored vesicles observed in dopamine-beta hydroxylase- and norepinephrine-immunopositive cells. These results demonstrated that dopamine-beta-hydroxylase and norepinephrine-immunopositive, as well as chromaffin cells, were identical to the cells which take up exogenous norepinephrine, described in part I of this study. However, many intermediate levels were found between norepinephrine-immunonegative and strongly norepinephrine-immunopositive glomus cells, suggesting that the distinction between these two kinds of cells is not clearcut. PMID- 1607880 TI - H-CAM expression in the human nervous system: evidence for a role in diverse glial interactions. AB - H-CAM (CD44/Hermes antigen) is an 85-95 kDa widely-distributed cell surface adhesion molecule that participates in diverse cellular interactions. It is an important cell surface receptor of hyaluronate, and has been implicated in the binding of circulating lymphocytes of endothelial cells in the process of lymphocyte homing. Here we define the immunohistological distribution of H-CAM in the human nervous system as a means of assessing its possible participation in nervous system ontogeny and function. H-CAM is widely expressed in human CNS white matter by subsets of glial cells, and within the neuropil of several grey matter structures. Neurons appear uniformly negative. H-CAM+ cells and processes are first detected at 20 weeks gestation in a diffuse subependymal pattern, and staining of the anchoring processes but not the cortical extensions of radial glia is seen by 24 weeks. Beginning at 26 weeks, H-CAM+ astrocytes also demarcate fascicles of axons in developing white matter tracts, becoming diffusely distributed in all CNS white matter by full term gestation. In the mature CNS, fibrous and subpial astrocytes, glial outlines within the glomeruli of the cerebellar granule cell layer, Bergmann glia, and extraneuronal grey matter matrix in certain locations are H-CAM+. In reactive gliosis occurring in foetal and developed brains, H-CAM is strongly and uniformly expressed by GFAP+ astroglial cells. In the PNS, dorsal roots express substantially higher levels of H-CAM than ventral roots, and there is an accompanying inverse staining pattern displayed by weakly immunoreactive posterior horns and positive anterior horns. Also, there is an abrupt cessation of H-CAM expression at the junction of the central and peripheral segments of cranial nerves. These findings indicate the dynamic regulation of H-CAM expression in the developing human nervous system, and suggest the hyaluronate-binding activity and potentially other cell-cell or cell-matrix adhesive functions of H-CAM may play an important role in development of the nervous system. PMID- 1607881 TI - Rat Schwann cells can be induced to express major histocompatibility complex class II molecules in vivo. AB - Previous studies, showing that cultured rat Schwann cells could be induced to express MHC class II molecules, raised the possibility that Schwann cells in living nerves might, under some conditions, express MHC class II molecules and take part in activation of T lymphocytes. In the present work, the ability of myelin- and non-myelin-forming Schwann cells in vivo to express MHC class II molecules was investigated. Lymphokines or bacterial antigens were injected into the living sciatic nerve of adult rats. Examination of the nerves three days after injection of interferon-gamma or six days after injection of either tumour necrosis factor, antigens from mycobacterium leprae or whole mycobacteria leprae, revealed strong MHC class II immunostaining on some myelin-forming Schwann cells in the vicinity of the injection site. Very few non-myelin-forming cells expressed MHC class II molecules. MHC class II positive mononuclear cells were present in the injected nerves and endothelial cells of capillaries expressed high levels of MHC class II antigens. Crushing the sciatic nerve without injection of factors also induced MHC class II molecules on a few Schwann cells. Thus rat Schwann cells can be induced to express MHC class II molecules in vivo as in vitro. This strengthens the possibility that in living nerves Schwann cells are able to function as accessory cells in the initiation or augmentation of T cell-mediated immune responses. PMID- 1607882 TI - Report of the 17th International Joint Conference on Stroke and Cerebral Circulation. Phoenix, Arizona, 30 January-1 February, 1992. PMID- 1607883 TI - Monitoring of somatosensory evoked potentials during carotid endarterectomy. AB - Somatosensory evoked potentials (SEPs) were monitored in the course of 368 carotid endarterectomies (CEAs) carried out in 312 patients. In an initial group of 26 patients the shunt was used routinely while in a second group, involving 342 CEAs, it was applied selectively on the basis of modifications which the SEP underwent during clamping. The criterion for shunting was the progressive reduction, up to 50%, of the N20-P25 amplitude. New postoperative neurological deficits appeared in 6 patients, all of whom displayed a transitory SEP flattening. The SEPs of 2 of these returned to normal by the time they awoke and both showed a clinical deficit homolateral to the operated side. In only 2 cases did the deficit fail to regress completely and their postoperative CT scans revealed ischaemic lesions. A positive relationship emerged between SEP changes and back pressure values; nonetheless, as many as 75% of the patients with low residual back pressure values (less than 25 mmHg) tolerated the clamping. SEP monitoring appears to provide a reliable basis for selectively applying a shunt when there is a high risk of haemodynamic ischaemia during clamping. PMID- 1607884 TI - Alzheimer's disease: identical phenotype of familial and non-familial cases. AB - Ninety outpatients with Alzheimer's disease according to ICD-10 diagnostic draft criteria were studied to test the hypothesis that cases with a familial aggregation are different from cases without such an aggregation with respect to cognitive impairment. In all cases the diagnosis of Alzheimer's disease was confirmed by prospective observation within 12 months of initial evaluation. Patients were divided into two groups: one consisting of 23 patients with a familial aggregation, the other consisting of 67 patients without secondary cases among first-degree relatives. By means of t-tests differences in impairment of cognitive functions between the groups were calculated. The results did not yield statistically significant differences between the groups for any of the neuropsychologically investigated cognitive deficits. Thus the hypothesis that the presence of a familial aggregation may lead to a distinct phenotype in Alzheimer's disease was not confirmed. PMID- 1607885 TI - Motor responses evoked by magnetic brain stimulation in psychogenic limb weakness: diagnostic value and limitations. AB - The latencies and amplitudes of responses evoked by magnetic brain stimulation (magnetic evoked potentials, MEP) in the first dorsal interosseus and the anterior tibial (TA) muscles were investigated in 15 patients with psychogenic limb weakness and in 50 patients with limb weakness due to established organic central nervous system disease. Of the patients with psychogenic limb weakness, 3 presented with upper limb monopareses, 2 with lower limb monoparesis, 4 with hemipareses, 4 with parapareses and 2 with paraparesis. All patients with psychogenic weakness had MEP in arm and leg muscles with latencies within the normal range. MEP amplitudes were also normal except for 1 patient in whom the response amplitude in the TA of the plegic limb was reduced. In patients with limb weakness due to established organic disease, MEP were frequently but not invariably abnormal. In patients with plegic (i.e. completely paretic, MRC grade 0) muscles due to organic disease, MEP always were clearly abnormal. Normal MEP were sometimes elicited from paretic muscles, more commonly in association with cerebral hemisphere lesions than with spinal lesions. We conclude that psychogenic limb weakness is associated with normal MEP. However, normal MEP in mildly paretic muscles do not definitely exclude organic pathology. PMID- 1607886 TI - Head-injured subjects aged over 50 years: correlations between variables of trauma and neuropsychological follow-up. AB - Neuropsychological follow-up was studied in 70 consecutive head-injured subjects aged over 50 years. Diffuse deterioration (28%), moderate deterioration (25%) and dementia (21%) were the most frequent sequelae. Analysis of correlations between neuropsychological sequelae and trauma variables showed that: (1) mild trauma did not necessarily imply good prognosis and could be followed by very severe consequences; (2) duration of post-traumatic amnesia was correlated with coma duration but not with neuropsychological outcome; (3) on the whole, no prognostic predictor of the outcome was found. PMID- 1607887 TI - Epilepsy as the presenting feature of neuroacanthocytosis in siblings. AB - A brother and sister developed epilepsy at the age of 28 and 30 years respectively, and were subsequently found to have neuroacanthocytosis. The brother developed tics, and a tendency to self-mutilate a year later, but his sister had not developed any movement disorder in the 5 years since the onset of epilepsy. In families with epilepsy, the diagnosis of neuroacanthocytosis should be considered, particularly when one family member has tics or other involuntary movements. PMID- 1607888 TI - Headache caused by craniospinal pressure dissociation in the Arnold-Chiari syringomyelia syndrome. AB - Two patients with Arnold-Chiari malformation, associated with syringomyelia, are described. They presented with headache caused by coughing, sneezing and straining. The pathogenesis and diagnosis are discussed. The treatment of this condition consists in a fossa posterior decompression, in some cases followed by a syringoperitoneal or a syringosubarachnoid shunt. PMID- 1607889 TI - Fluorescent probe analysis of muscle plasmalemma in Duchenne's progressive muscular dystrophy. AB - The relationship between fluorescence intensity and binding of 1-anilino naphthalene-8-sulphonate (ANS) to muscle plasmalemma in patients with Duchenne's muscular dystrophy (DD) and controls was studied. The fluorescence of ANS was markedly enhanced in DD as compared with controls. The magnitude of this enhancement was increased by monovalent and divalent cations; treatment of DD plasmalemma with trypsin caused an opposite effect. Treatment with phospholipase A and C altered the ANS fluorescence in DD and controls equally. These findings may indicate an increase of the hydrophobic character in the apolar-polar interface of DD plasmalemma. The relationship of these changes to a lack of dystrophin in DD remains to be established. PMID- 1607890 TI - Neopterin concentrations in serum and cerebrospinal fluid in HTLV-I infected individuals. AB - The concentration of neopterin was measured in serum samples taken from individuals infected with HTLV-I: 5 from asymptomatic individuals, 1 from a patient with adult T-cell leukaemia and 30 from patients with tropical spastic paraparesis (TSP). In addition, cerebrospinal fluid (CSF) was available from 22 of the TSP patients and neopterin concentrations were determined in these. Elevated levels of neopterin were found in only 3 of the 36 HTLV-I-positive serum samples, all from TSP patients, but significantly elevated neopterin levels were observed in 12 of the 22 CSF samples. The localisation of the elevated neopterin concentrations to the CSF of patients with TSP suggests a marked degree of activation of the cell-mediated immune system intrathecally. This provides further evidence in favour of powerful immune mechanisms operating centrally in the pathogenesis of TSP. PMID- 1607891 TI - A tactile maze test in unilateral spatial neglect: the influence of vision and recording technique. AB - Right brain-damaged patients with left spatial neglect were examined on a tactile maze task. They started to explore the right side of the maze and their search times were longer on the left side. Their performance was the same whether blindfolded or not, which contrasts with the results of other studies and probably reflects differences in task demand. The present results do not support a previous observation that visual neglect can be compensated through the tactile modality. Our patients had markedly longer search times than normal controls in the right as well as the left hemifield, and search times in both hemifields were positively correlated. The outcome of the maze test in this context may therefore depend to a large extent on impaired topographical processing. PMID- 1607892 TI - Somatosensory evoked potentials, sensory nerve potentials and sensory nerve conduction in hereditary motor and sensory neuropathy type I. AB - Thirty-nine patients from six families with hereditary motor and sensory neuropathy type I and control subjects were included in this study. A neurological deficit score (NDS) was derived from a neurological examination and compared with neurophysiological test findings. Further, sensory nerve conduction velocities (SNCV) were compared with the motor nerve conduction velocities (MNCV). Five patients whom peaks of N11/N13 complex and N20 of the median nerve sensory evoked potential (SEP) could be recorded showed normal interpeak latency. The interpeak separation P14-N20 measured in six patients was normal. These findings point to the normal function of the central conductive pathways. Erb and cervical potentials of the median nerve SEP could be recorded in 10% and 12% of the patients, respectively. In contrast, about half of the patients showed a scalp N20, while in most of them no SNCV could be measured. In six patients far field potential P14 of the median nerve SEP was the first detectable potential. Therefore, we argue in view of the anatomical structure of the thalamus, that the first generator for synchronizing and amplification of impulses is probably located in the thalamus. A third of the patients had a cortical sural nerve SEP, while no sural nerve potentials could be recorded. No association was found between the SEP findings and the NDS. There was an inverse correlation between median SNCV and the NDS, but no relationship between the former and sensory deficit alone. In 40% of the patients median SNCV and in 13% sural SNCV could be recorded and considered to be severely decreased.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607894 TI - A syndrome of early onset spinocerebellar ataxia with optic atrophy, internuclear ophthalmoplegia, dementia, and startle myoclonus in a Sri Lankan family. PMID- 1607893 TI - A comparative study of methods for estimation of presynaptic inhibition. AB - The influence of vibration on the H-reflex and on the tendon reflex amplitudes was compared and the efficacy of both methods for the assessment of the presynaptic inhibition was studied. One hundred and twenty patients with post stroke spastic hemiparesis were investigated. Muscle tone, muscle force and tendon reflexes were assessed. The H-reflex and the Achilles tendon reflex (TA) were recorded under identical experimental conditions. Vibration at a frequency of 100 Hz and an amplitude of 2 mm was applied to the TA. Just after vibration the maximal amplitudes of both reflexes were measured. The ratios of reflex amplitudes after vibration to normal maximal reflex amplitudes (Hvibr/Hmax and TAvibr/TAmax) were evaluated. In all patients with hemiparesis the healthy side was used as a control. Our results revealed significantly increased amplitude ratios on the spastic side. Hence it is concluded that presynaptic inhibition is decreased in spasticity. The amplitude ratios on the healthy and the spastic side were consistent. There was good positive correlation between Hvibr/Hmax and TAvibr/TAmax ratios, suggesting that they provide similar and reliable estimates of presynaptic inhibition. PMID- 1607895 TI - Cerebral venous thrombosis as a cause of neonatal focal clonic seizures. PMID- 1607896 TI - A bibliography of publications on observer variability (final installment). PMID- 1607897 TI - Sensitivity and specificity of a single diagnostic test in the presence of work up bias. AB - A diagnostic test is put into routine use by being applied to a population with unknown test status and unknown disease status. All subjects with a positive test are then referred to a "gold standard" assessment for the disease. Subjects with a negative test are normally not referred to the "gold standard" assessment. In some cases, the investigators may refer a small random sample of subjects with a negative test to the "gold standard" assessment in order to determine if they really do not have the disease. If "gold standard" results are not available on an entire population, it is well-known that work-up bias, or sequential-ordering bias, exists. In this situation, classical equations for sensitivity and specificity give biased results. This paper describes an equation for estimation of prevalence, and two new equations which calculate sensitivity and specificity from prevalence and predictive values, and which are appropriate for data from this type of "irregular observational design". PMID- 1607898 TI - The low cholesterol-mortality association in a national cohort. AB - The relationship of low serum cholesterol and mortality was examined in data from the NHANES I Epidemiologic Followup Study (NHEFS) for 10,295 persons aged 35-74, 5833 women with 1281 deaths and 4462 men with 1748 deaths (mean (followup = 14.1 years). Serum cholesterol below 4.1 mmol/l was associated with increased risk of death in comparison with serum cholesterol of 4.1-5.1 mmol/l (relative risk (RR) for women = 1.7, 95% confidence interval (CI) = (1.2, 2.3); for men RR = 1.4, CI = (1.1, 1.7)). However, the low serum cholesterol-mortality relationship was modified by time, age, and among older persons, activity level. The low serum cholesterol-mortality association was strongest in the first 10 years of followup. Moreover, this relationship occurred primarily among older persons (RR for low serum cholesterol for women 35-59 = 1.0 (0.6, 1.8), for women 70-74, RR = 2.1 (1.2, 3.7); RR for low serum cholesterol for men 35-59 = 1.2 (0.8, 2.0), for men 70-74, RR = 1.9 (1.3, 2.7)). Among older persons, however, the low serum cholesterol-mortality association was confined only to those with low activity at baseline. Factors related to underlying health status, rather than a mortality enhancing effect of low cholesterol, likely accounts for the excess risk of death among persons with low cholesterol. The observed low cholesterol-mortality association therefore should not discourage public health programs directed at lowering serum cholesterol. PMID- 1607899 TI - The feasibility of using a double blind experimental cross-over design to study interventions for sick building syndrome. AB - Methodological problems have limited scientific investigation of the causes of and solutions for sick building syndrome. The feasibility of using an experimental double blind cross-over study to resolve many of these methodological problems was assessed in a pilot study. The experimental intervention was to vary the amount of outdoor air from 10 cubic feet per minute per person (cfmpp) to 20 cfmpp or 50 cfmpp by central manipulation of the building heating, ventilation and air-conditioning (HVAC) system. Over 6 consecutive study weeks, 2 trials of rates were administered in random order. Study subjects and investigators of the study were blinded to intervention sequence. Unblinding, office environment rating and symptom occurrence were measured weekly. Of 305 eligible workers, 254 participated. Problems were encountered in delivering the lowest dose of ventilation due to building leakage. The prevalence of symptoms diminished steadily over the 6 study weeks, time trends which could be controlled by recommended design modifications. Blinding to the intervention was successfully maintained. Weekly non-response did not introduce a response bias but reduced the number of subjects available for analysis by one-third for each trial. We conclude that this design, with certain modifications, is feasible to evaluate many proposed interventions for sick building syndrome. PMID- 1607900 TI - Adapting a clinical comorbidity index for use with ICD-9-CM administrative databases. AB - Administrative databases are increasingly used for studying outcomes of medical care. Valid inferences from such data require the ability to account for disease severity and comorbid conditions. We adapted a clinical comorbidity index, designed for use with medical records, for research relying on International Classification of Diseases (ICD-9-CM) diagnosis and procedure codes. The association of this adapted index with health outcomes and resource use was then examined with a sample of Medicare beneficiaries who underwent lumbar spine surgery in 1985 (n = 27,111). The index was associated in the expected direction with postoperative complications, mortality, blood transfusion, discharge to nursing home, length of hospital stay, and hospital charges. These associations were observed whether the index incorporated data from multiple hospitalizations over a year's time, or just from the index surgical admission. They also persisted after controlling for patient age. We conclude that the adapted comorbidity index will be useful in studies of disease outcome and resource use employing administrative databases. PMID- 1607901 TI - Do patients' coronary risk factor reports predict acute cardiac ischemia in the emergency department? A multicenter study. AB - The objective of the present study was to determine whether the presence of the classical coronary risk factors increases the likelihood of acute cardiac ischemia beyond that expected from clinical presentation and electrocardiogram. Clinical data and reports of classical coronary risk factors were collected prospectively from 1743 patients without clinically obvious coronary disease. Patients were selected from 5773 emergency department patients at 6 hospitals who presented with symptoms suggesting acute ischemia. We used logistic regression to determine the relative risk of each risk factor report for acute ischemia. In women, the presence of classical risk factor reports does not increase the risk of acute ischemia. In men, only diabetes and family history of myocardial infarction significantly increase the risk (p less than 0.05). The relative risks are 2.4 and 2.1, respectively, and are small compared to those conferred by chest pain (12.1), an abnormal ST segment (8.7), or an abnormal T wave (5.3). For a patient presenting to the emergency department, the classical coronary risk factors convey minimal risk for acute cardiac ischemia, especially when compared to the overwhelming importance of the chief complaint and the ECG. PMID- 1607902 TI - A comparative study of the performance of screening tests for senile dementia using receiver operating characteristics analysis. AB - The discriminability of three types of test for the detection of senile dementia was assessed within a French sample of 155 normal elderly and 120 persons with mild or moderate senile dementia using Receiver Operating Characteristics (ROC) analysis. Results suggest that despite differences in the content of the three instruments, they are equally discriminant. Methods involving direct cognitive examination were found to lose discriminability in relation to milder forms of dementia, whereas an informant questionnaire was found to perform equally as well on cases of mild and moderate dementia. The informant questionnaire was also found to produce lower refusal rates and to be less influenced by the place of residence of the elderly person. The problem of selecting cut-off points according to the range of predicted prevalence rates of dementia for the general population is also discussed. PMID- 1607903 TI - Causal propositions in clinical research and practice. AB - The concept of causation is central to clinical research and practice. The health science literature on causality, largely contributed by epidemiologists, has examined the population-based question of whether an exposure can cause a given health outcome. Most of this literature has focused on criteria for assessing causality, rather than attempting to define it. Moreover, the population-based approach is rather distant from the individual persons in whom causes must act, which has led to different perspectives on causality among epidemiologists and health policy markers, on the one hand, and clinical practitioners and the lay public, on the other. We attempt to bridge the gap between these perspectives by defining three probabilistic causal propositions based on the locus (individual vs population) and time frame (past vs future outcome) to which they refer, beginning with the individual in whom a health outcome has already occurred ("retrodictive" causal propositions, i.e. It Did) and proceeding to "potential" causal propositions (It Can) for populations and "predictive" causal propositions (It Will) for individuals or populations. We conclude by showing how attention to these distinctions may help avoid common pitfalls that can impair clinical or public health decision-making. PMID- 1607904 TI - A simplified index of physical health for use in epidemiological studies. AB - A battery of simple questions designed to measure physical health, in terms of ability to perform physical activities, was appraised in 1839 men and women aged greater than or equal to 50 years in a community survey in Jerusalem. The number of "Yes" answers to six questions, five of which could be skipped if the first one was answered positively, was found to be a satisfactory index, with a high degree of consistency-reliability in the total sample (Cronbach's alpha coefficient = 0.97) and in subgroups categorized by sex, age, education, or father's region of birth. The index constituted an excellent Guttman scale (coefficient of reproducibility = 0.96, coefficient of scalability = 0.94), indicating that the score serves both as a measure of physical health and as an indication of the profile of capabilities. Associations with age and other variables conformed with expectations, attesting the construct validity of the index. PMID- 1607906 TI - Alcohol drinking and high blood pressure: data from a 1980 national cardiovascular survey of Japan. AB - Many epidemiological cross-sectional studies have confirmed that alcohol drinking is related to high blood pressure. However, the impact of alcohol drinking on high blood pressure in the general population including older people has only been reported on in a few studies. The association between alcohol drinking and blood pressure or the prevalence of hypertension was examined using cross sectional data of 4795 men and 6102 women aged 30-94, randomly selected from the Japanese population in 1980. The response rates were 74 and 84% for men and women, respectively. The prevalence of hypertension adjusted for body mass index (BMI, kg/m2) was significantly higher in everyday male drinkers than in male non drinkers from the youngest age group (30-39 years) to oldest age group (70 years and over). A relationship between alcohol and blood pressure was found only in the youngest age group (30-39 years) of female drinkers. In each 10-year age group of men, the BMI-adjusted systolic and diastolic blood pressures in everyday drinkers were 7-10 and 4-6 mmHg higher than those in non-drinkers. The relationship between alcohol and blood pressure in men was confirmed by multiple regression analysis adjusting for age and BMI in both younger (30-59 years) and older (60-94 years) people. The impact of alcohol drinking on blood pressure in men should be taken into account in the primary prevention of blood pressure related diseases and in the treatment of hypertension in both younger and older people. PMID- 1607905 TI - Social networks as predictors of ischemic heart disease, cancer, stroke and hypertension: incidence, survival and mortality. AB - Three social network measures were obtained from a randomly sampled cohort of 2603 HMO members in 1970-71. Mortality and first incidence of ischemic heart disease, cancer, stroke, and hypertension were assessed over the next 15 years. Outcome data were adjusted for age, sex, smoking, SES, and baseline health status. Persons with histories of a given morbidity at or prior to baseline were excluded from the analyses of that morbidity. Social network measures, particularly network scope (a measure of the number of different domains in which a person has social contacts), were powerful predictors of 15-year mortality hazard, but weak predictors of incident disease. Only network scope predicted IHD incidence, and none of the other morbidities was predicted by the social network measures. However, social network measures were strong predictors of both cause specific and all-cause mortality among persons who had incident cases of IHD, cancer, and stroke. These data suggest that social networks may be more effective in supporting recovery after illness has occurred than in preventing the incidence of new disease. PMID- 1607907 TI - Reflections of a 16th year clinical scholar. PMID- 1607908 TI - Collinearity and imprecision in dietary measurement. PMID- 1607909 TI - Assessing the use of medications in the elderly: methods and initial experience in the Cardiovascular Health Study. The Cardiovascular Health Study Collaborative Research Group. AB - The Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary heart disease and stroke, recruited 5201 community-dwelling adults aged 65 years or older. To assess the prevalence of medication use at baseline, we used the method of medication inventory and transcribed information about drug names and doses from prescription bottles. Using a specially-written computer program, persons without a knowledge of drug nomenclature coded 10,511 (89%) of the 11,846 medicines entered. We compared the results of the medication inventory and answers to questions on specific medications for reliability and validity. The use of beta-blockers and beta-agonists assessed by the method of medication inventory, but not by the method of directed recall, was associated with a significant effect on mean heart rate. Among 5197 participants with medication data, 76.1% were taking at least one medicine, and the mean number of drugs per person was 2.28. Among those with a reported history of high blood pressure, participants with cardiovascular disease (CVD) were more likely to be treated, and they were more likely to be taking beta-blockers and calcium-channel blockers than those without CVD. Daily aspirin use was also more common among those with CVD (30.5% of women and 43.2% of men) than among those without CVD (14.0% of women and 14.0% of men). The prevalence of post-menopausal estrogen use differed significantly among the four clinical centers (range = 5.5%-22.5% of women). We conclude that this method of assessing medications was easy to use and provided estimates of exposure to drugs that may affect risk of cardiovascular disease. PMID- 1607910 TI - Randomized trials in the treatment of cancer of the esophagus. PMID- 1607911 TI - Patterns of treatment failure and prognostic factors associated with the treatment of esophageal carcinoma with chemotherapy and radiotherapy either as sole treatment or followed by surgery . AB - PURPOSE: The records of patients with esophageal cancer who were treated with a combined modality therapy were reviewed to determine the effects of simultaneously administered chemotherapy and radiotherapy (RT) at sites of recurrence and the relationship between treatment outcome and clinicopathologic variables. PATIENTS AND METHODS: One hundred seventeen patients were treated with fluorouracil (800 mg/m2) [corrected] and cisplatin (80 mg/m2) combined with either 36 Gy (36 patients) or 54 to 60 Gy (35 patients) of RT as sole therapy. Forty-six patients underwent surgery after they had received chemotherapy and 36 Gy of RT as initial treatment. Patients with either squamous cell cancer (SCC) or adenocarcinoma were included. RESULTS: Complete endoscopic regression after an initial 36 Gy of RT and chemotherapy occurred in more than 50% of patients and in both tumor types. Relief of dysphagia accompanied tumor regression. Forty-two tumors were resected, and 11 showed a complete histologic response. Significant associations were demonstrated between enhanced survival and a diagnosis of SCC, a complete endoscopic response to initial chemotherapy and RT, and a tumor length of less than 5 cm. Multivariate analyses suggested that tumor length and complete endoscopic response were independent prognostic variables. The survival rate of patients treated by resection or radical-dosage RT was not significantly different. CONCLUSIONS: The relief of dysphagia demonstrates the palliative value of chemotherapy and RT in both tumor types. The similar survival rates of patients with SCC or adenocarcinoma treated either surgically or with high-dose combined therapy (54 to 60 Gy) emphasize the need to evaluate the role of surgery and combined treatment in randomized studies. PMID- 1607912 TI - Comparison of a novel assay for breast cancer mucin to CA15-3 and carcinoembryonic antigen. AB - PURPOSE: To compare the sensitivity and specificity of an automated microparticle enzyme immunoassay (MEIA) for breast cancer mucin (IMx BCM; Abbott Laboratories, North Chicago, IL) to that of CA15-3 and carcinoembryonic antigen (CEA) for detecting and monitoring breast cancer. MATERIALS AND METHODS: IMxBCM was compared to assays of CA15-3 and CEA in 630 serum specimens from healthy women, and from women with breast cancer, other malignancies, benign breast conditions, or other benign diseases. RESULTS: Analysis of the log-transforms for the three markers in all specimens showed a high correlation of IMxBCM with CA15-3 (r = .78), but not with CEA (r = .25). Based on a receiver-operating-characteristics (ROC)-curve analysis for any given specificity, IMxBCM was found to be a more sensitive marker than either CA15-3 or CEA for distinguishing 105 women with advanced or metastatic breast cancer from 89 healthy women (P = .003 and P = .04, respectively), from 98 women with benign breast conditions (P = .02 and P = .002), or from 191 women with benign diseases (P = .03 and P less than .0001). At 95% specificity, the sensitivities of IMxBCM, CA15-3, and CEA for detecting advanced or metastatic breast cancer were 69%, 51%, and 30%, respectively. Serial serum samples (n = 177) were analyzed in 20 additional metastatic breast cancer patients with measurable disease. Serial IMxBCM levels corresponded with the clinical course of disease in 80%, CA15-3 in 65%, and CEA in 60% of the 20 patients. CONCLUSIONS: Increased sensitivity of IMxBCM, despite a high correlation with CA15-3, suggests that IMxBCM and CA15-3 may recognize distinct epitopes on the same molecule. Although further research is indicated, IMxBCM may provide a promising marker in the clinical management of breast cancer patients. PMID- 1607913 TI - A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study. AB - PURPOSE: A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS: From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS: As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION: Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma. PMID- 1607914 TI - Prognosis and treatment of lymphoblastic lymphoma in adults: a report on 80 patients. AB - PURPOSE: We analyzed prognostic factors in 80 adult patients with lymphoblastic lymphoma (LBL). PATIENTS AND METHODS: Twenty-one patients received six monthly courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and maintenance chemotherapy for 12 months. The LNH-84 protocol (30 patients) consisted of four courses of high-dose CHOP followed by consolidation for 4 months. Both FRALLE (22 patients) and LALA (seven patients) protocols were two intensive chemotherapy regimens for acute lymphoblastic leukemia (ALL) that included an induction with daunorubicin, vincristine, cyclophosphamide, prednisolone (and asparaginase for the FRALLE regimen), consolidation, and maintenance chemotherapy that lasted for 2 years. RESULTS: Sixty-six patients (82%) achieved a complete remission (CR). The CR duration rate and overall survival rate at 30 months were estimated to be 46% and 51%, respectively, with a median follow-up of 55 months. Only two of 37 relapses occurred after 26 months. Chemotherapy protocol did not influence CR rate, CR duration, and survival. A higher CR rate was associated with an age of less than 40 years, lactic dehydrogenase (LDH) level of less than two times the upper limits of normal, and no or one extranodal site of disease. Short survival was associated with a failure to achieve CR, age older than 40 years, B symptoms, LDH level more than two times the upper limits of normal, and hemoglobin level of less than 100 g/L. Bone marrow involvement had no prognostic value. We could not evaluate precisely the prognostic value of Ann Arbor stage because inclusion criteria differed among treatment groups. CONCLUSION: Our findings suggest that age and LDH are two important pretreatment prognostic factors for adult LBL, and that the optimal prognostic staging system remains a controversial issue. PMID- 1607915 TI - High-dose salvage chemotherapy without bone marrow transplantation for adult patients with refractory Hodgkin's disease. AB - PURPOSE: For patients with Hodgkin's disease (HD) who do not achieve complete response (CR), who experience a relapse within the first year of CR, and for those who have two or more relapses, the outcome is poor. Salvage chemotherapy regimens at conventional doses produce a CR rate that ranges from 10% to 50% and a 5-year disease-free survival (DFS) between 10% and 25%. On the other hand, high dose chemotherapy regimens given in combination with bone marrow transplantation (BMT) produce a CR rate that ranges from 40% to 80% and a 3-year DFS of approximately 40%. We report the 5-year results of a prospective study in patients with refractory HD who were treated with three courses of intensive chemotherapy without BMT. PATIENTS AND METHODS: Thirty-nine adult patients with refractory HD were treated with three courses of intensive chemotherapy. Each cycle of chemotherapy comprised vindesine 1 mg/m2/d in continuous intravenous (IV) infusion from day 1 to day 5; Adriamycin (doxorubicin; Roger Bellon Laboratories, Neuilly, France) 40 mg/m2/d in continuous IV infusion from day 1 to day 3; carmustine 140 mg/m2/d at day 3; etoposide 200 mg/m2/d from day 3 to day 5; and methylprednisolone 120 mg/m2/d from day 1 to day 5. After the third cycle of chemotherapy, irradiation (20 Gy) was performed whenever possible and depended on previous irradiation. RESULTS: At the end of the treatment, 31 patients (79%) were in CR. Among these patients, 10 relapsed after a median time of 3 months. The overall 5-year survival rate was 46%. The freedom from progression (FFP) and the freedom from treatment failure (FFTF) rates were 48% and 43%, respectively. The main toxicities were hematologic (neutropenia and thrombocytopenia) and digestive. Four patients died due to treatment-related complications (two from septic shocks, one from respiratory insufficiency, and one from posttransfusional AIDS). CONCLUSION: The results of this study seem to be comparable to those results obtained with high-dose chemotherapies with autologous BMT. PMID- 1607916 TI - A phase III trial comparing idarubicin and daunorubicin in combination with cytarabine in acute myelogenous leukemia: a Southeastern Cancer Study Group Study. AB - PURPOSE: A randomized clinical trial was undertaken to compare the therapeutic effectiveness of idarubicin (IDR) to daunorubicin (DNR), and both were given in combination with cytarabine (CA) in acute myelogenous leukemic (AML) patients. PATIENTS AND METHODS: Newly diagnosed patients were given a daily infusion of CA (100 mg/m2) for 7 days and were assigned randomly to receive DNR (45 mg/m2) or IDR (12 mg/m2) daily for the first 3 days. Those patients who achieved a complete remission (CR) were given three consolidation courses that consisted of CA (100 mg/m2 intravenously [IV]) and thioguanine (TG; 100 mg/m2 orally) every 12 hours for 5 days and either DNR (50 mg/m2) or IDR (15 mg/m2) on the first day of each cycle. After consolidation, patients received late intensification, which consisted of the same drugs used for induction except that the CA was given for 5 days and the anthracycline for 2 days. Four courses were planned at 13-week intervals. RESULTS: The CR rates were 75 of 105 (71%) on the IDR arm and 65 of 113 (58%) on the DNR arm (P = .03). The median survival and median remission durations were 297 and 433 days, respectively, on the IDR arm. The median survival and median remission durations were 277 and 328 days, respectively, on the DNR arm. Six deaths occurred during late intensification, five on IDR and one on DNR; this approach was abandoned after 47 patients were entered. The median survival was significantly longer for patients who received late intensification. CONCLUSION: This trial demonstrated that IDR was more effective than DNR in remission induction in AML. PMID- 1607917 TI - Phase II study of subcutaneous interleukin-2 in unselected patients with advanced renal cell cancer on an outpatient basis. AB - PURPOSE: A single-institution phase II study was undertaken to evaluate the efficacy and toxicity of interleukin-2 (IL-2) administered by subcutaneous injection. PATIENTS AND METHODS: Twenty-seven unselected patients (15 male) with a mean age of 60 years (range, 42 to 76 years) who had advanced renal cell cancer were treated as outpatients. IL-2 was given once a day, 5 days per week for 6 weeks. During the first 5-day cycle, 18 x 10(6) IU was given once daily; in the following cycles, the doses in the first 2 days were reduced to 9 x 10(6) IU. After a 3-week rest period, treatment was repeated in patients who had a response or stable disease (SD). To prevent pyretic reactions, patients also received acetaminophen (250 to 500 mg given orally every 4 to 6 hours). RESULTS: After 6 weeks, 26 patients were assessable for response. Two patients (8%) had a complete remission (CR), four (15%) had a partial remission (PR), and 13 (50%) had SD. A second cycle of 6 weeks was given to 19 patients; one patient with a PR and six with SD showed progression. Duration of the CR was 17+ and 19+ months, and length of the PR was 2, 8, 11, and 11+ months. The median survival of the patients who were nonresponders and responders was 10 and 20+ months, respectively, and for all patients was 13 months. One patient died as a result of myocardial infarction and brain stem ischemia. Systemic side effects in the other patients were tolerated and accepted, and included transient inflammation and local induration at the injection sites, fever and chills, and nausea. CONCLUSION: Subcutaneous IL 2 is clinically active, has an acceptable toxicity, and can be given to patients with concomitant disease. PMID- 1607918 TI - A phase II trial of interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma. AB - PURPOSE: A phase II trial that used a regimen of interleukin-2 (IL-2) and interferon alfa-2a (IFN-alpha) was undertaken to evaluate the efficacy of this combination in the treatment of metastatic renal cell carcinoma. PATIENTS AND METHODS: Thirty-four assessable patients were treated with one to two induction cycles of IL-2 administered by continuous intravenous (IV) infusion at a dose of 3 x 10(6) U/m2/d [corrected] for 4 days per week plus IFN-alpha administered by subcutaneous injection at a dose of 5 x 10(6) U/m2/d [corrected] for 4 days per week for 3 consecutive weeks. A maintenance regimen of IL-2 2 x 10(6) U/m2/d [corrected] given by continuous IV infusion for 5 days per week plus IFN-alpha subcutaneously at a dose of 6 x 10(6) U/m2/d [corrected] that was given 3 days per week for 3 weeks was administered for one to five cycles. Twenty-eight patients (82%) completed one to two induction cycles, and 14 patients (41%) received maintenance doses. RESULTS: Major responses were achieved in four patients (12%), which included one complete response (CR) in a bone metastasis. Responses were observed in patients both with and without prior nephrectomy as well as in a primary tumor. Toxicity was moderately severe and included two treatment-related deaths. CONCLUSIONS: In view of the minimal antitumor activity and associated toxicity, the combination of IL-2 and IFN-alpha in this trial cannot be recommended. The investigation of new cytokines and the identification of biologic prognostic factors for a response to immunologic therapy are essential. PMID- 1607919 TI - The toxic and hematologic effects of interleukin-1 alpha administered in a phase I trial to patients with advanced malignancies. AB - PURPOSE: A phase I trial was undertaken because interleukin-1 alpha (IL-1 alpha) possesses antiproliferative, immunostimulatory, antiinfection, myeloprotective, and myelorestorative properties that could be beneficial in cancer treatment. PATIENTS AND METHODS: In this phase I trial, IL-1 alpha was administered intravenously (IV) during a 15-minute period daily for 7 days to patients with advanced solid malignancies. RESULTS: The maximum-tolerated dose (MTD) of IL-1 alpha alone was 0.3 microgram/kg. A second group of patients received indomethacin plus IL-1 alpha based on preclinical studies, which indicated that indomethacin could abrogate IL-1 alpha-induced hypotension; however, the MTD of IL-1 alpha plus indomethacin was 0.1 microgram/kg lower than IL-1 alpha alone. Fever, chills, headache, nausea, vomiting, and myalgia were common but were not dose-limiting. Hypotension resulted from a marked decrease in systemic vascular resistance and required pressors at 0.3 and 1.0 micrograms/kg IL-1 alpha. Dose limiting toxicities included hypotension, myocardial infarction, confusion, severe abdominal pain, and renal insufficiency. IL-1 alpha treatment caused a significant, dose-related increase in the total WBC count (mainly segmented neutrophils and neutrophilic bands). Bone marrow cellularity increased because of enhanced numbers of relatively mature myeloid cells and megakaryocytes. Platelet counts decreased during therapy but were significantly elevated above baseline values 1 to 2 weeks posttreatment; this may have been an effect of IL-6 that was shown to be induced by IL-1 alpha treatment. Significant increases in triglycerides, cortisol, C-reactive protein, thyroid-stimulating hormone and decreases in cholesterol, testosterone, and protein-C were observed with treatment. CONCLUSION: We conclude that at doses of IL-1 alpha that can be given safely to cancer patients, significant, potentially beneficial hematopoietic effects occur. PMID- 1607920 TI - Association of HLA phenotype with response to active specific immunotherapy of melanoma. AB - PURPOSE: Only a proportion of patients with disseminated melanoma who were immunized successfully with a therapeutic melanoma vaccine (theraccine) had a major clinical response. We investigated whether there was a correlation between their HLA phenotypes and the likelihood of a clinical response. PATIENTS AND METHODS: Seventy patients with disseminated melanoma who were treated with melanoma theraccine were HLA-typed serologically. The two melanoma cell lines used in the theraccine also were typed by serology and cDNA probes (for class II). Results were analyzed to see whether any alleles were present or absent in responders consistently. RESULTS: The HLA class I alleles A2 (and the cross reacting A28), B12 (and its split B44 and B45), and C3 were found to be associated with clinical remission. The effects of these alleles on response were apparent when two or more of the alleles were analyzed together. There was a 38% response rate in those 24 patients with two or three of the alleles compared with 20% in the group as a whole. CONCLUSIONS: These data support two distinct possibilities between which we cannot yet distinguish. Responses may be more likely when there is a close match between the HLA molecules in the theraccine and the patients' own molecules. Alternatively, certain types of HLA class I molecules present in the patients may facilitate rejection of autochthonous melanomas by efficiently presenting melanoma-associated antigens to cytotoxic T cells. PMID- 1607921 TI - Influence of sex and age on fluorouracil clearance. AB - PURPOSE: Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl. PATIENTS AND METHODS: Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2). RESULTS: 5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2. CONCLUSIONS: These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment. PMID- 1607922 TI - Pharmacokinetics and metabolism of 4'-iodo-4'-deoxy-doxorubicin in humans. AB - PURPOSE: 4'-iodo-4'-deoxydoxorubicin is a new anthracycline that currently is under clinical evaluation. To improve the management of future trials, we have determined its pharmacokinetics and metabolism during a phase I/II study and have tried to relate the parameters obtained to the hematologic toxicity of the drug in terms of the survival of blood cells. PATIENTS AND METHODS: The pharmacologic study included 19 patients who were entered at dose levels that ranged between 6 and 90 mg/m2; nine patients were treated at 80 mg/m2, which is close to the maximum recommended dose level. Blood sampling was performed from the end of the bolus infusion to 48 hours after treatment. Drug and metabolites were extracted and analyzed by high-performance liquid chromatography (HPLC), and the data were processed by nonlinear fitting to multicompartment models. RESULTS: Plasma concentrations were best fitted to a three-compartment model with half-lives of 5.2 minutes, 0.79 hours, and 10.3 hours. The total body clearance and volume of distribution at steady state were high (350 L/h/m2 and 2,065 L/m2). The drug was metabolized extensively to a 13-dihydroderivative, 4'-iodo-4'-deoxy doxorubicinol; the mean area under the curve (AUC) ratio metabolite/parent drug was the highest observed ever for an anthracycline (12.1 +/- 7.4); the metabolite was cleared from the plasma with an elimination half-life of 15.3 hours. The AUCs of the parent compound and its metabolite were related linearly to the dose administered, and showed no saturation phenomenon. Urinary excretion was studied in nine patients and showed a cumulative elimination of less than 6% of the dose administered, two thirds of which were eliminated in the first 12 hours after injection. Ninety-three percent to 100% of the elimination of fluorescent compounds occurred in the form of the metabolite. Drug concentration in five tumor samples showed a rapid uptake of the drug from plasma and a preferential uptake of the parent drug compared with the metabolite. Blood cell counts after 4'-iodo-4'-deoxydoxorubicin treatment showed significant correlations among the surviving fractions of both granulocytes and platelets and the AUCs of the parent drug and its metabolite; the most significant correlations were obtained for the granulocytes and the metabolite. Significant correlations between AUCs and blood cell survivals were maintained, even if only the nine patients treated at the dose of 80 mg/m2 were taken into account for the computation. CONCLUSIONS: Our results especially show that myelosuppression that is induced by 4'-iodo-4' deoxydoxorubicin can be well predicted by the measure of the AUC of the drug and its metabolite. This could be used for the further development of the drug toward high-dosage schedules. PMID- 1607924 TI - Impact of time on cosmetic outcome following breast-conserving therapy. PMID- 1607923 TI - Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow. AB - PURPOSE: Acute and chronic graft-versus-host disease (GVHD) continues to be the major causes of morbidity and mortality after allogeneic bone marrow transplantation (BMT). In this study, we have evaluated the clinical effects of selective in vitro T-cell depletion of donor allogeneic bone marrow by using a single monoclonal antibody ([MoAb] anti-T12, CD6) and rabbit complement. This antibody recognizes mature T cells, but not other cellular elements such as natural-killer (NK) cells, B cells, and myeloid precursors. PATIENTS AND METHODS: From August 1983 to April 1991, 112 consecutive adult patients with hematologic malignancies underwent BMT with bone marrow from HLA-identical sibling donors. Marrow was harvested and depleted of mature T lymphocytes ex vivo by the use of three rounds of incubation with an anti-T12 antibody and rabbit complement. The preparative regimen consisted of cyclophosphamide and fractionated total body irradiation (TBI) in 108 patients. No patients received prophylactic immune suppression post-BMT. Purgation by anti-T12 was used as the only method for the prevention of GVHD. RESULTS: Twenty patients (18%) developed acute GVHD (grade 2 to 4); only eight patients developed chronic GVHD. The incidence of GVHD did not increase significantly with age. Only three of 112 patients (2.7%) exhibited acute graft failure. One patient developed late graft failure that was associated with cytomegalovirus (CMV) infection. Within the subset of 50 patients who had not previously undergone unsuccessful conventional therapy (acute leukemia in first remission or chronic myelogenous leukemia [CML] in stable phase), we estimated by the Kaplan-Meier method that the probability of disease-free survival was 50% at 3 years post-BMT, with a median follow-up of 44 months. The treatment-related mortality rate in this group was only 14% and was independent of patient age. CONCLUSIONS: We conclude that selective in vitro T-cell depletion with an anti-T12 monoclonal antibody effectively reduces the incidence of both acute and chronic GVHD after allogeneic BMT without compromising engraftment. Moreover, depletion of CD6-positive cells from donor marrow obviates the need to administer immune suppressive medications to the majority of patients. This approach reduces the morbidity and mortality of allogeneic BMT and permits the BMT of older patients. PMID- 1607925 TI - Expression of the H-ras oncogene induces potassium conductance and neuron specific potassium channel mRNAs in the AtT20 cell line. AB - Expression of the EJ-ras oncogene in the AtT20 cell line results in several changes in their properties that correspond to a switch of these anterior pituitary-derived cells to a more neuronlike phenotype. The width of action potentials following transfection with ras is reduced 20-fold from over 200 msec in control AtT20 cells to less than 10 msec in ras-transfected cells. This is associated with a two- to threefold increase in the density of voltage-dependent potassium currents. In addition, the rate of inactivation of these currents is decreased approximately twofold in ras-transfected cells. At least part of the change in potassium current may be due to differential expression of potassium channel mRNAs. In the ras-transfected cells, mRNA species were detected using a probe for the voltage-dependent potassium channels, Kv4, a species that appears to be uniquely expressed in the nervous system, and NGK2, an alternatively spliced product transcribed from the same gene. These mRNAs are not detected in control AtT20 cells. The results suggest that the ras protein modulates the phenotype of excitable cells by influencing the expression of specific potassium channels and thereby altering the density and types of channels in the plasma membrane. PMID- 1607926 TI - Analysis of in vitro glucose utilization in a circadian pacemaker model. AB - An in vitro glucose utilization method, based upon 14C-2-deoxyglucose kinetics in brain slices, has been used to study circadian rhythms in hypothalamic slices containing the suprachiasmatic nucleus (SCN). Spontaneous SCN metabolic activity in vitro is similar to that observed in vivo with higher metabolic rates in subjective daytime and lower rates during subjective night. However, in vitro SCN metabolic activity during late subjective day is above that seen when glucose utilization is measured in vivo, suggesting that an inhibitory influence normally active in vivo is lost during slice isolation. Incubation of slices containing SCN in the presence of TTX exposes a TTX-insensitive component of metabolic activity in early subjective day, supporting prior suggestions that glucose utilization by the circadian oscillator continues in the absence of Na(+) dependent action potentials. Studies with high Mg2+ concentrations are consistent with the hypothesis that most metabolic activity above the basal level observed with the glucose utilization method is related to synaptic activity. Pharmacological studies of the SCN brain slice model with radiotracers offer potential for analysis of both circadian rhythmicity and neural regulation. PMID- 1607927 TI - Central and peripheral neurite outgrowth differs in preference for heparin binding versus integrin-binding sequences. AB - Neurons of the CNS and PNS differ in their response to fibronectin (FN) and proteolytic fragments of FN. The 33 kDa C-terminal cell and heparin-binding fragment of FN, in particular, is a strong promoter of CNS neurite outgrowth. To define further the neurite-promoting activity of the 33 kDa fragment, and to investigate further the differences between PNS and CNS responses to FN and the 33 kDa fragment, we contrasted neurite outgrowth by CNS and PNS neurons on three synthetic peptides representing sequences from this fragment of FN: two heparin binding peptides, FN-C/H I and FN-C/H II (McCarthy et al., 1990), and an integrin binding peptide, CS1 (Humphries et al., 1987). Spinal cord (SC) neurons, from the CNS, differed from dorsal root ganglion (DRG) neurons, from the PNS, with respect to substratum preference for heparin-binding versus integrin-binding peptides. SC neurite outgrowth was greatest on the heparin-binding peptide FN-C/H II, while DRG neurite outgrowth was greatest on the a4 beta 1 integrin-binding peptide CS1. To test whether the difference in substratum preference was due to differences in the molecular mechanism by which SC and DRG neurons interact with the 33 kDa fragment of FN, anti-beta 1 integrin antibodies and/or soluble heparin were added to the cultures as potential inhibitors of integrin-mediated or proteoglycan mediated interactions with FN. SC neurite outgrowth was much more sensitive to the effect of heparin than anti-beta 1 integrin, indicating SC neurite outgrowth may involve predominantly a heparin-sensitive mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607928 TI - Voltage-activated calcium currents in identified neurons from a hydrozoan jellyfish, Polyorchis penicillatus. AB - Calcium currents were studied in isolated "swim motor neurons" from the jellyfish Polyorchis penicillatus, using the tight-seal, whole-cell, voltage-clamp technique. Two high-voltage-activated (HVA) currents were observed. The transient current, HVA-t, activated rapidly (time to peak, 4 msec), inactivated with two time constants (26 msec, 187 msec) in a positive voltage range (Vi = -23 mV), and was larger when carried by calcium than by barium ions. The sustained current, HVA-s, inactivated slowly or not at all, even at very positive voltages and had the same amplitude whether carried by Ca2+ or Ba2+. It is likely that the two HVA current components arise from distinct channel populations, because the ionic selectivity of calcium channels is not known to depend on their inactivation kinetics. A third current appeared to activate at very positive voltages, and at a slower rate than did HVA-t. It is likely to be an artifact of inhomogeneous space clamping. A low-voltage-activated, cadmium-insensitive calcium current may also be present. Calcium currents in this primitive, multicellular animal have properties similar to calcium currents in other phyla; however, they do not fit neatly into the "T, N, L" classification scheme of vertebrate calcium currents. PMID- 1607929 TI - Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat. AB - The ventral striatum is characterized by an intricate neurochemical compartmentation that is reflected in the distribution of most of its afferent fiber systems. In the present study, the compartmental relationships of ventral striatal neurons projecting to the mesencephalon were studied by combining tract tracing with the immunohistochemical localization of leu-enkephalin. Injections of the retrograde tracer cholera toxin subunit B were placed at various sites in the ventral mesencephalon. The anterograde tracer Phaseolus vulgaris leucoagglutinin was injected in single compartments in the rostrolateral part of the nucleus accumbens. The projections from the ventral striatum to the dopaminergic cell groups in the ventral mesencephalon and those to the substantia nigra pars reticulata originate from distinct subpopulations of ventral striatal neurons that respect neurochemically defined compartmental boundaries. In the "shell" of the nucleus accumbens, neurons that project to the dopaminergic cell groups are located outside areas of high cell density and weak enkephalin immunoreactivity (ENK-IR). Rostrolaterally in the "core" of the nucleus accumbens, neurons inside large areas of strong ENK-IR surrounding the anterior commissure project to the dorsomedial part of the substantia nigra pars reticulata, whereas neurons outside these areas innervate the ventral tegmental area and/or the medial part of the substantia nigra pars compacta. By contrast, more caudally in the dorsal part of the nucleus accumbens and in the ventral part of the caudate-putamen, the relationships are reversed: neurons in- or outside small patches of strong ENK-IR project respectively to the pars compacta or the pars reticulata of the substantia nigra. Since the thalamic and cortical afferents of the ventral striatum are compartmentally ordered as well, the present results imply that through the ventral striatal compartments information from disparate combinations of cortical and thalamic sources may be conveyed to distinct mesencephalic targets. The component of the ventral striatomesencephalic system reaching the dopaminergic cell groups A10, A9, and A8 may modulate the dopaminergic input to virtually the entire striatum. The other component can, by way of the pars reticulata of the substantia nigra, participate in nigrothalamic and nigrotectal output pathways of the basal ganglia. PMID- 1607930 TI - Antibody neutralization of neurite growth inhibitors from oligodendrocytes results in expanded pattern of postnatally sprouting retinocollicular axons. AB - After early postnatal ablation of one superior colliculus together with the ipsilateral eye in Syrian hamsters, retinofugal fibers abnormally cross the tectal midline and innervate the remaining superior colliculus. The fibers of this aberrant decussation are confined mainly to the superficial gray layer, with little ingrowth or termination in the deeper stratum opticum; laterally, most termination is in the superficial part of the superficial gray. Establishment of this abnormal pattern is temporally correlated with the appearance of oligodendrocytes at progressively more superficial locations in the colliculus. Oligodendrocytes express, on their surface, molecules that are inhibitory to neurite growth. This raises the possibility that their differential distribution in the superior colliculus during growth of retinal fibers is causally involved in the generation of the observed termination pattern. We tested this hypothesis by applying the monoclonal antibody IN-1, which neutralizes this inhibitory activity, during the time of postnatal fiber growth and terminal arbor formation. We found that in the presence of IN-1, but not a control antibody, recrossing retinofugal fibers, observed at postnatal day 12, traverse the stratum opticum as well as the superficial gray, with greater depth of termination in superficial gray and stratum opticum. This pattern resembles that of the normal contralateral retinotectal projection. The results indicate that neurite growth inhibitors expressed by oligodendrocytes are responsible for restricting the innervation of a target area in postnatal plasticity. PMID- 1607931 TI - Effect of intracellular injection of inositol trisphosphate on cytosolic calcium and membrane currents in Aplysia neurons. AB - Pacemaker cells of Aplysia californica display a regular bursting that results from a complex interplay of Ca(2+)-mediated conductances and a continuous influx and extrusion of Ca2+. The effect of the second messenger 1,4,5-inositol trisphosphate (InsP3) on intracellular free Ca2+ concentration (Cai) regulation and electrical properties was investigated in identified neurons of the abdominal ganglion (R15, L2-L4, L6). Double-barreled Ca-selective microelectrodes were used to pressure inject InsP3 and measure Cai at the same point. Brief injection of InsP3 resulted in an average increase of Cai of 9.2 +/- 10.0 microM (+/- SE; n = 14) that decayed in about 1 min. The InsP3-induced elevation of Cai increased in a dose-dependent manner and saturated when large amounts of InsP3 were injected. The InsP3-induced Cai increase was the result of mobilization from intracellular stores; Cai could be repeatedly mobilized by InsP3 in cells superfused with 0 Ca artificial seawater for more than 60 min. Following multiple injections of InsP3, there was no evidence of immediate inhibition or facilitation. the spatial nature of the InsP3-induced Cai increase was investigated by moving the double-barreled Ca-selective microelectrode tip in a stepwise manner relative to the membrane surface. The largest InsP3-induced Cai increases were measured in an area 0-80 microns from the membrane surface; some cells had their largest InsP3-induced Cai increase some 120-160 microns away from the membrane. Injection of InsP3 in a bursting neuron induced an immediate train of action potentials followed by membrane hyperpolarization and a decrease in the burst frequency. Injection of InsP3 in voltage-clamped cells induced a biphasic response: a rapid inward current followed by a more prolonged outward current; the temporal overlap of the currents was depth dependent. Injection of InsP3 or Ca2+ from a double-barreled injecting electrode induced currents that were different in waveform and time course, indicating that part of the conductance change induced by InsP3 is direct and not mediated by the mobilized Ca2+. In BAPTA [1,2-bis(2-aminophenoxy)ethane N,N,N',N'tetra-acetic acid]-loaded cells, the InsP3-induced inward current was mostly unaffected while the Ca-induced outward current was largely attenuated. The results suggest that InsP3 mobilizes Ca2+ from discrete intracellular compartments and induces distinct changes in membrane currents that seem to be independent of the Cai increase. PMID- 1607932 TI - Characterization of a novel synapse-specific protein. I. Developmental expression and cellular localization of the F1-20 protein and mRNA. AB - A molecular description of the nerve terminal will be required to understand synaptic function fully. The goals of this study were to contribute toward such a description by characterizing a novel synapse-specific protein. A monoclonal antibody library was screened for antibodies to synaptic proteins. The antibodies were then used to isolate cDNA clones by expression screening. Here we report a detailed characterization of the protein reactive with monoclonal antibody F1-20. Immunohistochemical and biochemical analyses revealed that the F1-20 protein is synapse associated. Western blot analyses revealed that the F1-20 protein is a brain-specific polypeptide with an apparent molecular weight on SDS-PAGE of 190,000 Da. Northern blot analyses indicated that probes generated from an F1-20 cDNA clone hybridize to a single brain-specific mRNA of approximately 4.8 kilobases. In situ hybridization experiments demonstrated that F1-20 mRNA expression is neuronal specific. Northern and Western blot analyses indicated that F1-20 mRNA levels increase abruptly at postnatal day 4 and protein levels increase abruptly at postnatal day 7. This corresponds to a period of active synaptogenesis and synaptic maturation in the mouse CNS. We characterized the neuroanatomical distribution of the F1-20 protein by immunohistochemistry, and of the F1-20 mRNA by in situ hybridization. We found that the F1-20 mRNA and protein are expressed nonuniformly in brain. Variation in the expression of the F1-20 protein is complex and reveals patterns also exhibited by probes directed against other synapse-associated molecules. The highest levels of F1-20 protein are found in the cortically organized regions of the brain. The highest levels of F1-20 mRNA are found in long-distance projection neurons. There is also variation in the expression of F1-20 mRNA between different classes of large output neuron, as well as extensive variation in the expression of F1-20 mRNA between different nuclear groups. PMID- 1607933 TI - Characterization of a novel synapse-specific protein. II. cDNA cloning and sequence analysis of the F1-20 protein. AB - The F1-20 protein is a novel neuronal-specific, synapse-associated protein that is expressed nonuniformly in mouse brain. Expression of the F1-20 protein is developmentally regulated in a pattern coincident with active synaptogenesis and synaptic maturation. Here we report the cloning of the cDNA sequence for the F1 20 protein. We found two distinct isoforms of F1-20 cDNA that differed by the presence of 15 additional nucleotides, which does not interrupt the open reading frame. RNase protection analysis and PCR amplification of mouse brain RNA revealed that both isoforms are present in cellular RNA. It is likely that the two F1-20 mRNA isoforms are derived from RNA splicing events utilizing alternative 3' acceptor sites. Analysis of the deduced amino acid sequence for the complete open reading frame revealed that the predominant F1-20 mRNA encodes an 896 amino acid polypeptide with a molecular weight of 91,319 Da. The deduced amino acid sequence does not contain a signal sequence, or any extensive hydrophobic regions. The deduced amino acid sequence does contain a number of consensus sequences for protein kinases. Searches of the protein and nucleic acid sequence data bases revealed that the F1-20 protein has not been previously characterized at the primary structure level, although a weak similarity was found between rabbit calpastatin and the C-terminal portion of the F1-20 protein. We then determined biochemically that the F1-20 protein is a substrate for Ca(2+) dependent proteolysis, which is specifically inhibited by calpain inhibitors in vitro. This indicates that the F1-20 protein is a substrate for neuronal calpain. We observed that treatment of a synaptosomal lysate with alkaline phosphatase led to an increase in the electrophoretic mobility of the F1-20 protein, as well as to an increase in the sharpness of the electrophoretic band. This indicates that the F1-20 protein is phosphorylated in vivo. PMID- 1607934 TI - Excitatory amino acid regulation of intracellular Ca2+ in isolated catfish cone horizontal cells measured under voltage- and concentration-clamp conditions. AB - [Ca2+]i was measured using fura-2-loaded isolated catfish horizontal cells in the presence of L-glutamate and the glutamate analogs kainate (KA), quisqualate (QA), and NMDA. Caffeine was used to release Ca2+ from intracellular stores. Cell membrane potential was controlled with a voltage clamp to prevent activation of voltage-dependent Ca2+ channels in the presence of agonist. All excitatory amino acid agonists produced a rapid and sustained rise in [Ca2+]i with the order of potency being QA greater than Glu greater than KA greater than NMDA. The agonist induced [Ca2+]i increase was blocked in reduced [Ca2+]o and by 6-cyano-7 nitroquinoxaline-2,3-dione and 2-amino-5-phosphonopentanoate, which are specific blockers for QA/KA and NMDA receptors, respectively. The metabotropic receptor agonist trans-1-amino-1,3-cyclopentanedicarboxylic acid (ACPD; 10-200 microM) had no effect on [Ca2+]i. Hill coefficients from curves fitted to concentration response data suggested an amplification of the Ca2+ signal that was interpreted as calcium-induced calcium release (CICR) from intracellular Ca2+ stores. Caffeine (10 mM) produced a rapid transient rise in [Ca2+]i, confirming the existence of a Ca(2+)-sensitive store. Following caffeine-induced depletion of Ca2+ from intracellular stores, agonists were still able to produce increases in [Ca2+]i, confirming Ca2+ influx through the agonist-gated channel. The agonist induced increase in [Ca2+]i was decreased following caffeine-induced depletion, confirming a process of CICR. These results are consistent with the hypothesis that excitatory amino acids can produce direct modulation of [Ca2+]i by influx through the agonist-gated channel and by CICR from intracellular stores. PMID- 1607935 TI - Organization of cortical cytoskeleton of cultured chromaffin cells and involvement in secretion as revealed by quick-freeze, deep-etching, and double label immunoelectron microscopy. AB - We have studied the organization of the cytoskeleton in both unstimulated and stimulated cultured chromaffin cells, as well as its relationship with their secretory process by exocytosis. We found the spatial heterogeneity in the intensity of cortical rhodamine-phalloidin staining within a cell. The overall staining pattern or intensity was minimally altered after stimulation, although dopamine-beta-hydroxylase (DBH) antigen, a marker for the chromaffin granule membrane, was exposed preferentially on the plasma membrane areas with lower intensity of rhodamine-phalloidin staining. Using the quick-freeze, deep-etch technique, we found the heterogeneity in the organization of cortical cytoskeletal networks--some regions have actin filament bundles running parallel to the plasma membrane interspersed between granules and the plasma membrane, while others have few actin filaments beneath the plasma membrane before stimulation. Actin filaments were rarely observed in the inner cytoplasm. We did not observe the overall change in its organization after stimulation. Double label immunogold EM using anti-DBH antibody and anti-actin antibody combined with statistical analysis showed that (1) DBH was exposed on the plasma membrane preferentially where actin was sparse after stimulation (significant at less than 0.1%), although (2) regions having sparse actin were not always the sites for DBH exposure, and (3) the cortical actin zone was sometimes disrupted at the DBH exposed sites after stimulation. The present data suggested that (1) secretion is related to heterogeneous organization of cortical cytoskeleton after stimulation and (2) massive synchronized reorganization of the cytoskeleton in the whole cell is not necessary for secretion, although small changes of the cytoskeleton might occur under local regulation at each exocytotic site at the moment of the release. PMID- 1607936 TI - Visual processing of motion-defined form: selective failure in patients with parietotemporal lesions. AB - The following psychophysical data were obtained from 13 patients with unilateral cerebral hemispheric lesions and 20 control subjects: speed thresholds for detecting and for recognizing motion-defined letters, speed thresholds for detecting coherent motion and for discriminating its direction, and visual acuity for recognizing letters of 96% and 11% contrast. Acuity was between 6/6 and 6/3 for all patients. Four patients showed a selective loss of ability to recognize motion-defined letters, while the ability to detect those same letters was spared, as was the ability to detect coherent motion and discriminate its direction (type I loss). Three patients showed a loss of ability both to recognize and to detect motion-defined letters, while the ability to detect coherent motion and discriminate its direction was spared (type II loss). All seven patients who failed to recognize motion-defined letters had extensive lesions in parietotemporal white matter underlying Brodmann cortical areas 18, 19, 37, 39, 21, and 22. The lesion was in the left hemisphere for three patients and in the right hemisphere for the remaining four. The region of overlap in these seven patients was not invaded by the lesion in any of the other six patients, and none of these six patients showed a loss of ability to recognize motion-defined letters. Three patients showed selective loss of acuity for low contrast letters with normal Snellen acuity. The lesions in these three patients extended more posteriorly than in any other patient, and their region of overlap was in white matter underlying areas 18 and 19. We conclude that (1) the loss of ability to recognize letters in seven patients was specific to motion-defined letters rather than being a general loss of letter-recognition ability, (2) this visual loss was specific to motion-defined form rather than being a general failure of motion processing, and (3) the visual loss was not produced by lesions that did not involve the localized cerebral region specified above. To explain the existence of type I and of type II loss with sparing of the detection and discrimination of coherent motion, we propose that motion information is processed hierarchically. We further suggest that homologs of the socalled motion and color/form pathways (i.e., areas V1/MT/MST/7a and areas V1/V4/IT) are interconnected to form a distributed system that is important for the recognition of motion-defined form.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1607937 TI - Neuronal processes that underlie expression of kindled epileptiform events in the piriform cortex in vivo. AB - Recent studies with kindling and convulsant drug models of epilepsy suggest that the piriform (primary olfactory) cortex may be particularly susceptible to generation of epileptiform activity. The present study has examined the generation of interictal epileptiform events in the piriform cortex of kindled rats in vivo, taking advantage of special features of this system that facilitate physiological analysis. The investigation included analysis of extracellular and intracellular potentials, and membrane currents computed by current source density (CSD) analysis. In pyramidal cells, epileptiform events consisted of an initial EPSP that occurred in all-or-none fashion and a long-lasting IPSP with Cl(-)- and K(+)-mediated components. Onset of the IPSP was sufficiently fast that firing evoked by the EPSP was consistently limited to single action potentials. CSD analysis revealed the presence of two distinctly different excitatory epileptiform currents: an initial inward current of unknown origin that is widely distributed over depth, and a second much larger inward current at the depths of proximal apical and basal dendrites of pyramidal cells. It was concluded that this second component is mediated by the associational projections of pyramidal cells excited by the first component. Since these heavy associational projections also extend to neighboring areas including the amygdala, entorhinal cortex, and insular and orbitofrontal areas of neocortex, this second component could be widely propagated within the basal forebrain. An important finding was that the EPSP generated by this associational pathway was completely blocked in cell bodies of pyramidal cells in piriform cortex by the IPSP during most events. This IPSP may therefore play a critical role in limiting seizure activity by preventing reverberating positive feedback in the pyramidal cell population. It can be speculated that compromise of this IPSP, as by repetitive activation by the shock trains used for kindling, leads to prolonged epileptic activity in the piriform cortex and the many limbic structures to which it projects. PMID- 1607938 TI - Two pharmacologically and kinetically distinct transient potassium currents in cultured embryonic mouse hippocampal neurons. AB - Transient potassium currents in mammalian central neurons influence both the repolarization of single action potentials and the timing of repetitive action potential generation. How these currents are integrated into neuronal function will depend on their specific properties: channel availability at the resting potential, activation threshold, inactivation rate, and current density. We here report on the voltage-gated transient potassium currents in embryonic mouse hippocampal neurons dissected at embryonic days 15-16 and grown in dissociated cell culture for up to 3 d. Two transient potassium currents, A-current and D current, were isolated based on steady state inactivation and sensitivity to 4 aminopyridine (4-AP) and dendrotoxin (DTx). A-current had an activation threshold of approximately -50 mV and was half-inactivated at approximately -81 mV. A current relaxations at voltages between -40 and +40 mV could be fit by single exponential functions with time constants of 20-25 msec; these time constants showed little sensitivity to voltage. In contrast, D-current had an activation threshold of between -40 and -30 mV and was half-inactivated at approximately -22 mV. D-current inactivation was voltage dependent; time constants of fitted exponential functions ranged from approximately 7 sec at -40 mV to 200 msec at +40 mV. A slower component of inactivation was also evident. D-current was preferentially blocked by 4-AP (100 microM) and DTx (1 microM). Operationally, A- and D-currents could be cleanly separated based on conditioning pulse potential and 4-AP sensitivity. Total transient potassium current amplitude increased during the time that neurons were in culture (recordings were made between 2 hr after dissociation and 3 d in culture). When normalized for cell capacitance (an index of membrane area), A-current density (pA/pF) decreased and D-current density increased, even during a period between days 1 and 3 when total transient current density remained constant. This observation suggests that A- and D currents may be reciprocally modulated. Since blockade of D-current (with 100 microM 4-AP) increased both action potential duration and repetitive firing in response to constant current stimulation, long-term modulation of the A-current:D current ratio may affect the excitability of hippocampal neurons. PMID- 1607939 TI - ON- and OFF-pathways form separate neural substrates for motion perception: psychophysical evidence. AB - We have tested the hypothesis that in humans the signals carried by ON- and OFF pathway respectively are processed for the perception of motion by two distinct physiological substrates. In vertebrates, onset of a bright visual stimulus is signaled to the CNS by ON-center retinal ganglion cells; onset of a dark stimulus is transmitted by OFF-center cells. We chose apparent motion generated by successive presentation of two adjacent lines as a stimulus. Lines presented on a bright background were either darker or brighter than this background. Delayed onset of a pair of bright or dark lines elicits apparent motion at the same time fulfilling the constraint of stimulating either ON- or OFF-center ganglion cells, respectively. We determined the threshold delay needed for subjects to perceive the temporal order of the onset of the two lines for various angular separations. The threshold delay for a pair of bright lines stayed low for separations from 2' to 7'. The threshold delay for a pair of dark lines was low only within a narrow range of separations centered around 3'. The variation of thresholds with line distance must reflect the existence of a limited processing zone for the perception of motion. The diameter of the processing zone for bright lines is about twice as large as that for dark lines. This suggests that in humans the separation of ON- and OFF-pathways extends to the early stages of motion perception. To test this hypothesis independently, thresholds were determined when a bright and a dark line were presented in succession. This was done for a separation of 3' where thresholds for a pair of lines with equal contrast are similarly low. Temporal order was perceived correctly only when the delay was at least two to four times as high as the threshold delays found for the equal contrast stimuli. PMID- 1607940 TI - Reconstruction of action potential development from whole-cell currents of differentiating spinal neurons. AB - The duration and ionic dependence of action potentials are developmentally regulated. Voltage-clamp recordings of amphibian spinal neurons have revealed alterations in five currents. To determine whether the changes in the currents are sufficient to produce the change in action potential duration and ionic dependence, we constructed a Hodgkin-Huxley model of electrical excitability of these neurons. The model shows that the equations describing the voltage-clamped currents of young and mature neurons generate action potentials appropriate in duration and ionic dependence for each developmental stage. Moreover, the observed changes in the currents are quantitatively sufficient to produce the changes in the action potential. The effect of the change in each current is detectable in the model. However, the increase in amplitude of the delayed rectifier potassium current has the largest effect. The model further shows that changes in action potential duration could be achieved with changes in kinetics rather than amplitude of this current, or with changes in amplitudes of other currents. Thus, although increase in amplitude of the delayed rectifier plays a pivotal role in the maturation of excitability, it is not uniquely positioned to govern the action potential duration. PMID- 1607941 TI - Spatial and temporal expression of alpha- and beta-thyroid hormone receptor mRNAs, including the beta 2-subtype, in the developing mammalian nervous system. AB - Thyroid hormone exerts profound effects on the developing mammalian brain, and its deficiency can lead to severe mental retardation and motor abnormalities. To identify specific anatomic targets of thyroid hormone action in the developing mammalian nervous system, we examined thyroid hormone receptor gene expression by hybridization histochemistry on serial adjacent sections from 12 stages of the developing rat nervous system. 35S-labeled cRNA probes were generated from divergent sequences of rat alpha 1-, alpha 2-, beta 1-, and beta 2-thyroid hormone receptor and related cDNAs. We found that alpha- and beta-thyroid hormone receptor genes have distinct patterns of spatiotemporal expression in the embryonic and postnatal rat nervous system. alpha 1- and alpha 2-mRNAs were widely expressed in similar patterns; highest levels were found in the fetal neocortical plate, site of cortical neuronal differentiation. In contrast, beta 1 transcripts were restricted in distribution, with prominent expression in zones of neuroblast proliferation such as the germinal trigone and the cortical ventricular layer. Surprisingly, the "pituitary-specific" beta 2-transcript was detected in the developing hippocampus and striatum. Our results suggest that alpha- and beta-thyroid hormone receptors may play distinct functional roles during development of the mammalian nervous system. PMID- 1607942 TI - Lesions of the central nucleus of the amygdala, but not the paraventricular nucleus of the hypothalamus, block the excitatory effects of corticotropin releasing factor on the acoustic startle reflex. AB - Intracerebroventricular (icv) infusion of corticotropin-releasing factor (CRF) was previously found to produce a long-lasting, dose-dependent (0.1-1.0 microgram) increase in the amplitude of the acoustic startle reflex. The present study sought to determine where in the CNS CRF acts to increase startle. Intracisternal infusion of CRF (0.1-1.0 microgram) increased startle with a time course and magnitude similar to that produced by icv CRF, unlike intrathecal infusion, which produced a small, more rapid enhancement of startle. While lesions of the paraventricular nucleus of the hypothalamus had no effect on icv CRF-enhanced startle, bilateral lesions of the central nucleus of the amygdala significantly attenuated the excitatory effect of icv CRF but had no effect on intrathecal CRF-enhanced startle. Even though lesions of the amygdala blocked icv CRF-enhanced startle, local infusion of CRF into the amygdala did not significantly elevate startle. The present data indicate that the amygdala is part of the neural circuitry required for icv CRF to elevate startle, but does not appear to be the primary receptor area where CRF acts. The involvement of the amygdala in icv CRF-enhanced startle is consistent with the hypothesis that both the amygdala and CRF are critically involved in fear and stress. PMID- 1607943 TI - Noradrenaline depletion blocks behavioral sparing and alters cortical morphogenesis after neonatal frontal cortex damage in rats. AB - The possibility that cortical noradrenaline (NA) is necessary for sparing of function that occurs after neonatal frontal cortex damage was examined. Spatial localization by rats with frontal cortex damage on postnatal day 7 (P7) was better than that by rats with similar damage sustained as adults. The sparing was abolished in rats depleted of cortical NA by means of neonatal 6-hydroxydopamine (6HDA) administration. The blockade of sparing in the P7 frontal operates was associated with a smaller brain, thinner cortex, and reduced cortical dendritic branching relative to saline-treated P7 frontal operates. NA depletion alone in unoperated rats did not affect spatial learning but did reduce brain size and dendritic branching. Rats with frontal lesions on P4 did not show sparing of spatial localization, and 6HDA administration had no additional behavioral effect. Overall, these data are consistent with the notion that NA has some general function in maintaining some forms of plasticity in posterior cortex. PMID- 1607944 TI - Microstimulation in visual area MT: effects on direction discrimination performance. AB - Physiological and behavioral evidence suggests that the activity of direction selective neurons in visual cortex underlies the perception of moving visual stimuli. We tested this hypothesis by measuring the effects of cortical microstimulation on perceptual judgements of motion direction. To accomplish this, rhesus monkeys were trained to discriminate the direction of motion in a near-threshold, stochastic motion display. For each experiment, we positioned a microelectrode in the middle of a cluster of neurons that shared a common preferred direction of motion. The psychophysical task was then adjusted so that the visual display was presented directly over the neurons' receptive field. The monkeys were required to discriminate between motion shown either in the direction preferred by the neurons or in the opposite direction. On half the trials of an experiment, we applied electrical microstimulation while monkeys viewed the motion display. We hypothesized that enhancing the neurons' discharge rate would introduce a directionally specific signal into the cortex and thereby influence the monkeys' choices on the discrimination task. We compared the monkeys' performance on "stimulated" and "nonstimulated" trials in 139 experiments; all trials within an experiment were presented in random order. Statistically significant effects of microstimulation were obtained in 89 experiments. In 86 of the 89 experiments with significant effects (97%), the monkeys indicated that motion was in the neurons' preferred direction more frequently on stimulated trials than on nonstimulated trials. The data demonstrate a functional link between the activity of direction selective neurons and perceptual judgements of motion direction. PMID- 1607945 TI - Alternatively spliced transcripts of the flp-1 gene encode distinct FMRFamide like peptides in Caenorhabditis elegans. AB - We have isolated and characterized several cDNAs and the corresponding genomic region of a gene encoding multiple FMRFamide-like neuropeptides from the nematode Caenorhabditis elegans. The gene, named flp-1, consists of six exons of which four encode FMRFamide-like peptides. The cDNA and genomic sequences revealed that two distinct transcripts are generated by the use of an alternative 3' splice acceptor site between exons 3 and 4. This alternative splice results in the substitution of AGSDPNFLRFG for one of the copies of SADPNFLRFG found in the other translation product. Based on PCR analysis of RNA from mixed-stage animals, both transcripts are expressed. This gene is the first example of a distinct FMRFamide-like peptide being derived from alternative splicing, suggesting a unique role for the substituted peptide in the animal. PMID- 1607946 TI - Retinal growth in foveated teleosts: nasotemporal asymmetry keeps the fovea in temporal retina. AB - Fish retinas continue to grow throughout life by adding neurons at the margin, with the result that cells born at a peripheral site are steadily displaced toward the center of the enlarging retina. This presents a functional problem for fish with specialized temporal areas such as a fovea--how to reconcile continual growth with the maintenance of a temporal location for the fovea. One possibility is that the retina grows asymmetrically, with most new retina added nasally, relatively little temporally. I have tested this hypothesis by evaluating retinal growth in marine teleosts from 15 families, both foveated and unfoveated. The pattern of growth was revealed by exploiting the fact that each new generation of ganglion cells sends its axons into the optic nerve as a cohort; small grains of the carbocyanine dye 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine were applied to various sites in the cross section of the optic nerves of adults, and the retrogradely labeled cell bodies in the retina were visualized in whole mounts. The labeled cells lay in annuli, each one a generation of ganglion cells. Representatives of seven of the families showed clearly asymmetric growth: the labeled annuli were close together on the temporal side and more distant nasally, the embryonic fissure curved from its ventral origin toward the temporal side, and in six of these families, labeled fibers from temporal retina skirted the fovea. Members of the other eight families, without specialized areas, had more symmetric retinal growth: labeled annuli were equally spaced on all sides, the embryonic fissure was vertical, and there were no skirting fibers. The following hypothesis is supported: the retina grows asymmetrically, and maintains the area for acute vision oriented toward the anterior field. PMID- 1607947 TI - Variable membrane glycoproteins in different growth cone populations. AB - The question of whether growth cones generated by different neurons contain distinctive membrane glycoproteins was examined. Growth cone particles (GCPs) were isolated from specific regions of fetal or early postnatal brain, and their membrane proteins were analyzed by 2D gel electrophoresis and Western blotting, using WGA as a probe. These blots were compared to those generated by synaptosomes from adult brain. The patterns reveal a number of WGA-binding glycoproteins that are uniformly present in these subcellular fractions and others that are found in GCPs from selected brain regions only. The results indicate, therefore, substantial pattern diversity for the different, restricted growth cone populations. Some of the WGA-binding glycoproteins seen in GCPs disappear with increasing age and are absent from synaptosomes, while others seem to become more prominent. One of the glycoprotein complexes present in all GCP and synaptosome fractions analyzed is gp93. It has an apparent molecular weight of 90-97 kDa and exhibits unusually high heterogeneity in GCPs from whole fetal brain. The gp93 complex covers a pI range from about 4.9 to about 6.4 and consists of at least 12 different species, probably isoelectric variants. In GCPs from different brain regions, the sets of gp93 species observed are different and characteristic. Neuraminidase digestion shifts the gp93 pattern to a more neutral pI but simplifies it only partially, indicating that variable sialic acid content explains the molecular diversity to some extent. Thus, gp93 is a glycoprotein complex whose members are expressed and/or posttranslationally processed differentially in different growth cone populations. Such a glycoprotein family may be involved in selective cell-cell recognition. PMID- 1607948 TI - A parsimonious description of motoneuron dendritic morphology using computer simulation. AB - Most quantitative descriptions of neuronal dendrite morphology involve tabulations of measurements and correlations among them. The present work is an attempt to extract from such data a parsimonious set of parameters that are sufficient to describe the quantitative features of individual and pooled dendrites, including their statistical variability. A relatively simple stochastic (Monte Carlo) model was devised to simulate branching dendritic trees. The necessary parameters were then derived directly from measurements of 64 completely reconstructed dendrites belonging to six gastrocnemius alpha motoneurons, labeled by intracellular injection of HRP. Comparison of actual and simulated dendrites was used to guide the process of parameter extraction. The model included only two processes, one to generate individual branches given their starting diameters and the second to select starting diameters for the daughter branches produced at dichotomous branching points. The stochastic process for branch generation was controlled by probability functions for branching (Pbr) and for terminating (Ptrm), together with a constant rate of branch taper. All model parameters were fixed by motoneuron measurements except for branch taper rate, which was allowed to vary within limits consistent with observed taper rates in order to generate the appropriate total number of branches. The simplest model (model 1), in which Pbr and Ptrm depended only on local branch diameter, produced simulated dendrites that fit many, but not all, characteristics of actual motoneuron dendrites. Two additional properties produced significant improvements in the fit: (1) a small but significant dependence of daughter diameters on the normalized starting diameter of the parent branch, and (2) a dependence of Pbr and Ptrm on distance from the soma as well as on local branch diameter. The process of developing this model revealed unsuspected relations in the original data that suggest the existence of fundamental mechanisms for morphological control. The final model succinctly describes a large amount of data and will enable quantitative comparisons between the dendritic structures of different types of neurons, regardless of their relative sizes. PMID- 1607949 TI - Functional influence of interlaminar connections in the hamster's superior colliculus. AB - The aim of this study was to determine the functional importance of intrinsic connections within the hamster's superior colliculus (SC) in the development of the visual responses of neurons in the deep layers of this nucleus. We used localized injections of lidocaine to block action potentials of fibers that passed through the superficial layers and injections of CoCl2 to block synaptic transmission in these layers. We also determined the morphology of a number of the deep layer cells recorded in these experiments by intracellular injection of HRP. Injection of lidocaine into the superficial layers completely abolished the visual- and/or optic chiasm-evoked responses of all 40 deep layer cells tested. Thus, fibers that either pass through or synapse in the superficial layers are necessary for the visual responses of deep layer neurons. Injections of CoCl2 restricted to the superficial layers significantly reduced the visual responsivity of 86% of 92 deep layer neurons tested and abolished the visual responses of 68% of these cells. Superficial layer injections of CoCl2 were equally effective in reducing the responses of neurons with dendrites that ascended into the superficial layers (all seven cells tested and recovered) and those of cells with dendrites restricted to the deep layers (six of seven cells tested and recovered). Injections of CoCl2 into the deep layers, in the region of the cell being recorded, significantly reduced the visual responses of 59% of 37 cells and abolished the visual responses of 40% of the neurons tested. Deep CoCl2 injections abolished the visual responses of three of four cells with dendrites restricted to the deep layers and only one of four cells with dendrites that ascended into the superficial layers. These results indicate that descending interlaminar axons from visually responsive superficial layer cells may be responsible for the visual responsivity of most neurons in the deep SC layers of hamster. Also, some deep layer neurons in this species may receive effective visual input through their dendrites that ascend into the superficial layers, where they are likely to be contacted by retinal axons or axon collaterals of superficial layer cells. PMID- 1607950 TI - Clinical outcome of radiosurgery for cerebral arteriovenous malformations. AB - The clinical outcomes are described for 247 consecutive cases of arteriovenous malformation (AVM) treated with the gamma knife between April, 1970, and December 31, 1983. Headache resolved in 65 (66.3%) of the 98 patients presenting with this symptom and improved in an additional nine (9.2%). Of 59 patients admitted with seizures, 11 (18.6%) became seizure-free without anticonvulsant medication and an additional 30 patients (50.8%) became seizure-free with anticonvulsant medication. Pre-existing neurological deficits improved or totally disappeared following radiosurgery in 56.7% of affected cases. This improvement presumably occurred within the frame of the natural history. The protective effect of the ionizing beams against hemorrhage in incompletely obliterated AVM's is analyzed. To assess the rate of rebleeding, probability estimates were calculated using both the person-year method and the Kaplan-Meier life table. With the person-year method the actual rebleed rate is not too different from the values observed in the natural history of the disease (2% to 3%/yr). Analysis by Kaplan-Meier life table estimates demonstrated a risk of nearly 3.7%/yr until 60 months after radiosurgery. Five years following treatment, the life table ends in a plateau which could be interpreted as an indication of decrease in the risk of hemorrhage. However, long flat regions at the right end of the life table do not imply that the real risk of rebleeding is negligible unless a large number of patients have been followed well into or beyond the flat region. PMID- 1607951 TI - Neurovascular compression and essential hypertension. PMID- 1607952 TI - An in vitro comparative study of conducting vessels and penetrating arterioles after experimental subarachnoid hemorrhage in the rabbit. AB - The reactivity of rabbit basilar artery and penetrating arteriolar microvessels was studied in vitro using an isometric-tension measurement technique and an isolated perfused arteriole preparation, respectively. Comparisons were made between reactivities of normal vessels and those obtained from animals subjected to experimental subarachnoid hemorrhage (SAH) 3 days prior to examination. Subarachnoid hemorrhage produced significant increases in basilar artery contraction in response to increasing concentrations of serotonin (5 hydroxytryptamine) (10(-9) to 10(-5) M) and prostaglandin F2 alpha (10(-9) to 10( 5) M) when compared to normal arteries. In addition, SAH attenuated the relaxing effect of acetylcholine following serotonin-induced contraction and of adenosine triphosphate after KCl-induced basilar artery contractions. In contrast to the changes observed in large arteries, cerebral microvessels did not demonstrate significant differences in spontaneous tone or in reactivity to a number of vasoactive stimuli including application of calcium, serotonin, and acetylcholine. On the other hand, small but significant changes in arteriolar responsiveness to changes in extraluminal pH and to application of KCl were noted. Findings from this study suggest that intracerebral resistance vessels of the cerebral microcirculation are not greatly affected by the presence of subarachnoid clot, in contrast to the large arteries in the basal subarachnoid space. The small changes that do occur are qualitatively different from those observed for large arteries. These findings are consistent with the observation of significant therapeutic benefit with the use of calcium channel blockers without changes in angiographically visible vasospasm in large vessels. It is likely, therefore, that calcium antagonists may act to decrease total cerebrovascular resistance at the level of the relatively unaffected microcirculation after SAH without changing large vessel diameter. PMID- 1607954 TI - Emergency embolectomy for embolic occlusion of the middle cerebral artery after internal carotid artery balloon test occlusion. Case report. AB - Balloon test occlusion of the internal carotid artery (ICA) is useful in preoperatively assessing the risk of temporary occlusion or permanent sacrifice of the carotid artery. The incidence of symptomatic complications from this procedure is 1.7%. The case is reported of a 57-year-old woman in whom a balloon test occlusion of the left ICA was attempted. She developed a left ICA dissection/occlusion with subsequent embolization to the left middle cerebral artery, leading to right-sided hemiplegia and expressive aphasia. She was successfully treated by an emergency embolectomy followed by surgical repair of the left ICA, with an excellent outcome. This case represents the most serious complication encountered by the authors in more than 300 balloon test occlusions. Means of avoiding this complication during balloon test occlusion as well as the important factors in managing this problem are emphasized. PMID- 1607953 TI - Occlusion of the pig superior sagittal sinus, bridging and cortical veins: multistep evolution of sinus-vein thrombosis. AB - Cerebral sinus-vein thrombosis may lead to severe hemodynamic changes, elevated intracranial pressure (ICP), and brain edema. It is supposed that progression of the thrombus from the sinus into bridging and cortical veins plays a key role in the development of these pathophysiological changes, but this hypothesis lacks experimental proof. The aim of this study, using a novel animal model of sinus vein thrombosis, was to evaluate the effects of a standardized occlusion of the superior sagittal sinus and its bridging and cortical veins on hemodynamic alterations, on brain water content, and on ICP in domestic pigs. In 10 animals, the middle third of the superior sagittal sinus was occluded with a catheter guided balloon. Five of these pigs received an additional injection of 1 ml fibrin glue into the superior sagittal sinus anterior to the inflated balloon, leading to an obstruction of bridging and cortical veins. In five control animals the balloon was inserted but not inflated. Five pigs underwent cerebral angiography. Four hours after occlusion, the brains were frozen in liquid nitrogen, and coronal slices were examined for Evans blue dye extravasation, regional water content, and histological changes. Occlusion of the superior sagittal sinus alone did not affect ICP or cerebral perfusion pressure (CPP). The additional injection of fibrin glue caused an obstruction of cortical and bridging veins as well as severe increases in mean (+/- standard deviation) ICP to 49.4 +/- 14.3 mm Hg, compared with 8.3 +/- 4.5 mm Hg in sham-treated controls and 7.1 +/- 3.9 mm Hg in animals with occlusion of the superior sagittal sinus alone. There was also a steep fall in the mean CPP to 34.2 +/- 19.6 mm Hg compared with 96.4 +/- 13.8 mm Hg in the control group. White-matter water content anterior to the occlusion site was elevated to 81.9 +/- 3.7 gm/100 gm frozen weight in the fibrin group as compared to 70.7 +/- 2.2 gm/100 gm in controls. Posterior to the occlusion site, water content did not differ among the three groups. Angiography demonstrated collateral flow via cortical and bridging veins in animals with occlusion of the superior sagittal sinus alone. Additional fibrin glue obstructed these collateral vessels. The data suggest a multistep process of pathophysiological alterations in patients with sinus-vein thrombosis and may explain why these patients present with a wide variety of symptoms: minor neurological deficits or headache might indicate thrombosis of the superior sagittal sinus and/or its bridging veins.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1607955 TI - Radiation therapy for juvenile pilocytic astrocytoma of the pituitary stalk. Case report. AB - A case of juvenile pilocytic astrocytoma of the pituitary stalk is reported. The patient presented with diabetes insipidus and growth retardation. Magnetic resonance (MR) imaging was useful in diagnosing the lesion. Although the tumor could not be completely removed by surgery, radiotherapy was effective and the residual tumor disappeared 6 months after irradiation. The patient's condition has remained stable and no recurrence has been observed by MR imaging in the 4 years since radiation therapy. PMID- 1607956 TI - Temporal lobe tumor demonstrating ganglioglioma and pleomorphic xanthoastrocytoma components. Case report. AB - The case is reported of a 16-year-old boy with a left temporal lobe tumor composed of a ganglioglioma and a pleomorphic xanthoastrocytoma. Histologically, the tumor had two different components. One component involved the cortex of the left posterior temporal lobe and showed an aggregation of neuronal cells with an astroglial stroma. Ultrastructurally, numerous dense-cored vesicles, diagnosed as ganglioglioma, were found in the neuronal cells. The other component involved the adjacent cortex and white matter of the left anterior temporal lobe and the surrounding subarachnoid space. This was composed of pleomorphic cells with many multinucleated giant cells and occasional foamy cells. Most of the tumor cells were positive for glial fibrillary acidic protein. These features correspond well to earlier descriptions of pleomorphic xanthoastrocytoma. At 24 months following total tumor extirpation, the patient is alive and has had no evidence of tumor recurrence. PMID- 1607957 TI - Isolated intramedullary spinal artery aneurysm presenting with quadriplegia. Case report. AB - The case is presented of an isolated intramedullary posterior spinal artery aneurysm at the C-2 level in a 3-year-old girl. Quadriplegia related to probable intramedullary hemorrhage was the presenting symptom. Magnetic resonance imaging revealed findings consistent with an intramedullary vascular lesion, and vertebral angiography confirmed this to be an aneurysm of the posterior spinal artery. No associated vascular abnormalities were noted, and the aneurysm was successfully resected. Previous reports of isolated spinal aneurysms are reviewed. PMID- 1607958 TI - Blood pressure and intracranial pressure-volume dynamics in severe head injury: relationship with cerebral blood flow. AB - Increased brain tissue stiffness following severe traumatic brain injury is an important factor in the development of raised intracranial pressure (ICP). However, the mechanisms involved in brain tissue stiffness are not well understood, particularly the effect of changes in systemic blood pressure. Thus, controversy exists as to the optimum management of blood pressure in severe head injury, and diverging treatment strategies have been proposed. In the present study, the effect of induced alterations in blood pressure on ICP and brain stiffness as indicated by the pressure-volume index (PVI) was studied during 58 tests of autoregulation of cerebral blood flow in 47 comatose head-injured patients. In patients with intact autoregulation mechanisms, lowering the blood pressure caused a steep increase in ICP (from 20 +/- 3 to 30 +/- 2 mm Hg, mean +/ standard error of the mean), while raising blood pressure did not change the ICP. When autoregulation was defective, ICP varied directly with blood pressure. Accordingly, with intact autoregulation, a weak positive correlation between PVI and cerebral perfusion pressure was found; however, with defective autoregulation, the PVI was inversely related to cerebral perfusion pressure. The various blood pressure manipulations did not significantly alter the cerebral metabolic rate of oxygen, irrespective of the status of autoregulation. It is concluded that the changes in ICP can be explained by changes in cerebral blood volume due to cerebral vasoconstriction or dilatation, while the changes in PVI can be largely attributed to alterations in transmural pressure, which may or may not be attenuated by cerebral arteriolar vasoconstriction, depending on the autoregulatory status. The data indicate that a decline in blood pressure should be avoided in head-injured patients, even when baseline blood pressure is high. On the other hand, induced hypertension did not consistently reduce ICP in patients with intact autoregulation and should only be attempted after thorough assessment of the cerebrovascular status and under careful monitoring of its effects. PMID- 1607960 TI - Precise terminology in scientific communications. PMID- 1607959 TI - Measurement of tumor resection volumes from computerized images. Technical note. AB - The authors describe a method for quantitation of the area and volume of the resection cavity in patients who have undergone surgery for brain tumors. Using a slide scanner and Image 1.27, a public domain program for the Apple Macintosh II computer, computerized tomography scans and magnetic resonance images can be digitized and analyzed for a particular region of interest, such as the area and volume of tumor on preoperative and postresection scans. Phantom scans were used to analyze the accuracy of the program and the program users. User error was estimated at 2%, program error was 4.5%. This methodology is proposed as a means of retrospectively calculating the extent of tumor resection. PMID- 1607961 TI - Traumatic Coma Data Bank data-collection protocol. PMID- 1607962 TI - Treatment of trigeminal neuralgia by ophthalmic anesthetic. PMID- 1607963 TI - Breakage of Mayfield head rest. PMID- 1607964 TI - Head-injured patients who talk and deteriorate. PMID- 1607965 TI - Jugular venous oxygen saturation monitoring. PMID- 1607966 TI - Aortic coarctation and remote cerebral fistulae. PMID- 1607967 TI - Dural fibromatosis. PMID- 1607968 TI - Long-term ictal monitoring with subdural strip electrodes: prognostic factors for selecting temporal lobectomy candidates. AB - Long-term electrocorticographic (ECoG) monitoring data from subdural strip electrodes are analyzed to determine factors associated with seizure-free outcome from anterior temporal lobectomy. A total of 89 consecutive patients with complex partial seizures, in whom long-term ictal video/scalp electroencephalographic monitoring was insufficient to localize their epileptogenic focus, were subsequently evaluated with long-term ictal ECoG monitoring using subdural strip electrodes. Each patient underwent anterior temporal lobectomy based on the ictal ECoG data and has been followed for at least 1 year. The following parameters were found to be statistically significant in predicting a seizure-free outcome: unilateral onset, electrical onset pattern beginning as fast spike trains, absence of frontal lobe background desynchronization at onset, and an interhemispheric propagation time of greater than 8 seconds. Electrocorticographic criteria that were not associated with seizure outcome included: right- versus left-sided onset, time from electrical to clinical ictal onset, focality of onset (number of strip electrode contacts involved), and stereotypical ECoG onset. When present, the interictal focus was concordant with the ictal focus in most patients (96%), but was falsely lateralizing in 4% of cases. It is suggested that these data should improve patient selection for temporal lobectomy when subdural strip monitoring is used during preoperative evaluation. PMID- 1607969 TI - Infection of cerebrospinal fluid shunts in infants: a study of etiological factors. AB - The aim of this study was to find reasons for the high incidence of cerebrospinal fluid shunt infections seen in neonates. Four-hundred sixty-six consecutive shunt operations were analyzed retrospectively in 294 children, and 60 children were studied prospectively by quantitative sampling of skin bacteria before surgery and by sampling open wounds, shunt catheters, surgical gloves, and airborne bacteria. In total, 110 strains of coagulase-negative Staphylococcus isolated from the skin of 53 children before surgery were then tested for bacterial adherence. Retrospectively, the infection rate for infants younger than 6 months old was 15.7% (28 of 178 procedures), compared with 5.6% (16 of 288 procedures) for older children (p = 0.0005). Of all infections, 67% were due to coagulase negative Staphylococcus. Age was the only major factor influencing the infection rate. Three of the 60 children studied prospectively developed postoperative shunt infections. All were younger than 6 months and all had high skin bacterial densities before surgery. Contamination during surgery was generally low, but correlated with the preoperative skin bacterial density. Strains of coagulase negative Staphylococcus with high bacterial adherence were more commonly found in neonates than in older children. High skin bacterial density in neonates before surgery was a risk factor for infection in this study. These results also suggest that there is selection of more virulent strains of coagulase-negative Staphylococcus on the skin of neonates. Prevention of shunt infections in this high-risk group could be facilitated by the reduction of skin bacterial density before surgery using chlorhexidine shampoos and by the elimination of contamination by skin bacteria during surgery using packs soaked in an antiseptic agent to isolate wound edges and glove-changing before handling the shunt. PMID- 1607970 TI - Selection and combination of various endovascular techniques in the treatment of giant aneurysms. AB - Between April, 1989, and January, 1991, a total of 19 cases of giant aneurysm were treated by the endovascular approach. The patients included seven males and 12 females aged 15 to 72 years. Detachable balloons, occlusion coils, and ethylene vinyl alcohol copolymer liquid were used as embolic materials. In seven cases, thrombosis of the aneurysmal sac and/or base was achieved while sparing the parent arterial flow, complete obliteration of the aneurysm was achieved in four of these. Of these four patients, the thrombotic material was a detachable balloon in two, a combination of a detachable balloon and coils in one, and occlusion liquid in one. In the other three cases, complete occlusion was not achieved; one aneurysm was occluded with a detachable balloon and two with coils. In 11 patients, the parent artery was occluded either by trapping or by proximal arterial occlusion, and all patients showed complete occlusion of the aneurysms. In one patient, a combined bypass procedure and parent artery occlusion was performed. Among the 19 cases in this series there were four transient ischemic attacks, one reversible ischemic neurological deficit, and one death due to aneurysmal rupture during the procedure. Two patients died in the follow-up period, one from pneumonia 2 months postoperatively and the other from acute cardiac failure 2 weeks following surgery. Both deaths were unrelated to the endovascular procedure. It is concluded that the endovascular treatment of giant aneurysms remains difficult because of the large and irregular shape of the aneurysmal base and thrombus in the aneurysmal sac. The proper selection and combination of the available endovascular techniques is therefore of critical importance. PMID- 1607971 TI - Long-term results of spinal accessory nerve-facial nerve anastomosis. AB - A number of methods have been developed to reduce the cosmetic and functional disability resulting from facial nerve loss. It has often been suggested that the major trunk of the spinal accessory nerve should not be sacrificed for providing dynamic facial function because of shoulder disability and pain. A review of Mayo Clinic records has revealed that, between the years of 1975 and 1983, 25 patients underwent spinal accessory nerve-facial nerve anastomosis using the major division (branch to the trapezius muscle) of the spinal accessory nerve. There were 11 males and 14 females, ranging in age from 16 to 60 years (mean 41 years). The interval between facial nerve loss and anastomosis was 1 week to 34 months (mean 4.62 months). The duration of follow-up study ranged from 7 to 15 years (mean 10.8 years). Twenty patients had no complaints or symptoms related to their shoulder or arm at the time of this review and no patient had significant shoulder morbidity. The facial function achieved was "minimal" in five cases, "moderate" in six, and good to excellent in 14. Most patients appeared to benefit significantly from the spinal accessory nerve-facial nerve anastomosis. The morbidity of the procedure seemed quite minimal even in the young and active. The authors continue to believe that the spinal accessory nerve-facial nerve anastomosis, even when using the major trunk of the spinal accessory nerve, is a very useful and beneficial procedure. PMID- 1607972 TI - The effect of changes in cerebral perfusion pressure upon middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation after severe brain injury. AB - Middle cerebral artery blood flow velocity and jugular bulb venous oxygen saturation (SJO2) were measured by transcranial Doppler (TCD) ultrasonography and continuous venous oximetry, respectively, in 41 severely brain-injured patients. The purpose of the study was to examine the relationships between TCD flow velocity, SJO2, and alterations in blood pressure (BP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP). In these patients, CPP was reduced either by rising ICP or by falling BP. Both forms of reduction of CPP resulted in a greater fall in diastolic flow velocity than other flow parameters. As CPP decreased below a critical value of 70 mm Hg, a progressive increase in TCD pulsatility index (PI) was observed (r = -0.942, p less than 0.0001), accompanied by a fall in SJO2 (r = 0.78, p less than 0.0001). At pressures above 70 mm Hg, there was no correlation of either PI or SJO2 with CPP. The relationship between PI and CPP held true in patients with both focal and diffuse pathologies and was the same whether changes in CPP resulted from alterations in ICP or BP. The PI and SJO2 correlated better with CPP than with ICP or BP. Transcranial Doppler ultrasonography can identify states of reduced CPP. Decreases in SJO2 with falling CPP suggested progressive failure of cerebral blood flow to meet metabolic demands. Monitoring of TCD and SJO2 may be used to define the optimum CPP level for management of severely brain-injured patients. PMID- 1607973 TI - Control of tremor and involuntary movement disorders by chronic stereotactic stimulation of the ventral intermediate thalamic nucleus. AB - The authors report on the long-term results of chronic stereotactic stimulation of the ventralis intermedius thalamic nucleus performed in 14 cases of disabling and intractable tremor. There were 10 patients with parkinsonian tremor and four with essential tremor. Three of the 10 parkinsonian patients had previously undergone contralateral thalamotomy. Tremor was assessed by clinical evaluation, surface electromyography, accelerometer, and videotape recordings before and after stimulation. The deep-brain electrode was implanted in the ventralis intermedius nucleus according to stereotactic procedure and connected to a subcutaneous pulse generator after a stimulation test period. Tremor suppression or reduction was obtained in all cases with high-frequency (130 Hz) stimulation. Marked functional improvement was maintained in 11 patients with a mean follow-up interval of 17 months. Levodopa-induced dyskinesias observed in five parkinsonian patients prior to surgery were improved or suppressed in four cases by thalamic stimulation. Stimulation was continued during the day and stopped at night in eight cases. Six patients were stimulated night and day to avoid a rebound effect which appeared as soon as the pulse generator was stopped. The only side effects were hand tonic posture in one case and persistent paresthesia in another case. The mechanism of action of this attractive treatment may be a functional alteration of the thalamic discharging area. The authors conclude that this technique is a good alternative to thalamotomy, especially when the risks of high frequency coagulation are severe in frail and older patients. PMID- 1607974 TI - Scoliosis in pediatric Chiari malformations without myelodysplasia. AB - A prospective study was undertaken in 1985 to better understand how the surgical manipulation of hindbrain herniation affected abnormal spinal curvature. Eleven patients under 16 years of age with Chiari malformation (not associated with myelodysplasia) and scoliosis of at least 15 degrees were studied. The mean curve angle at the time of original treatment was 29 degrees, with the convexity to the right in seven patients. The curvature was rapidly progressing in four patients. The most common presenting signs were myelopathy and weakness. Investigative procedures included spine radiographs with the patient standing and magnetic resonance (MR) imaging of the brain, spinal cord, and craniovertebral junction. Eight children had associated hydrosyringomyelia. Surgical intervention consisted of a dorsal posterior fossa decompression in all patients and a transoral ventral decompression of the cervicomedullary junction in five. All patients were followed at 3, 6, and 12 months, and at yearly intervals thereafter with clinical evaluations, spine radiographs in the standing position, and postoperative MR imaging. The mean follow-up period was 35 months. The scoliosis improved in eight patients, stabilized in one, and progressed in two. Only one child required postoperative spinal fusion and instrumentation for progression of scoliosis. Hematomyelia or hematobulbia was associated with persistent scoliosis in two patients. The presence of hydrosyringomyelia and bone erosion did not preclude curve improvement. All patients under 10 years of age had resolution of their scoliosis, despite preoperative curves of more than 40 degrees. These findings emphasize the importance of early surgical intervention, with the restoration of normal cerebrospinal fluid dynamics at the craniovertebral junction in children with symptomatic Chiari malformations. PMID- 1607975 TI - Clinical effect of intra-arterial tumor necrosis factor-alpha for malignant glioma. AB - Recombinant human tumor necrosis factor-alpha was administered intra-arterially to treat 20 cases of malignant gliomas, mostly progressive or recurrent. The optimum dosage was determined to be 1 x 10(5) U/sq m/day. Among the 10 evaluable patients treated at this dosage, two responded (one completely and one partially), resulting in a 20% response rate. Side effects were mild and easily controllable. Improvement of neurological symptoms was noted in 47% of the patients a few days after treatment, even when computerized tomography showed no tumor regression. This might have been due to the pleiotypic biological activity of tumor necrosis factor-alpha. Neuroradiographic observations revealed narrowing of the tumor-feeding artery, a decrease in tumor staining ability, and necrosis in the central part of a tumor. The authors suggest that intra-arterial administration of tumor necrosis factor-alpha may be an effective treatment for malignant glioma, including recurrent cases. PMID- 1607976 TI - Long-term follow-up study after extracranial-intracranial bypass surgery for anterior circulation ischemia in childhood moyamoya disease. AB - Between May, 1974, and March, 1991, 104 patients with moyamoya disease, all under 16 years old at the time of first surgery, underwent superficial temporal-to middle cerebral artery anastomosis and/or encephalomyosynangiosis. The mean follow-up period was 9.6 years (range 4.8 to 16.0 years). Hemiplegia was the most frequent symptom before the first operation. Transient ischemic attacks (TIA's) were noted in 57 patients and minor stroke with hemiplegia in 44. The most frequent type of cortical dysfunction was aphasia (21 cases). Postoperatively, the incidence of TIA's and/or completed stroke with motor weakness of the extremities was markedly decreased, but visual disturbance progressed and major or minor stroke with visual disturbance was found in two cases. In patients under the age of 3 years, a major stroke prior to surgery resulted in a poor outcome in 36% of cases. Preoperative major stroke in patients between the ages of 3 and 7 years was less frequent, and poor outcomes were seen in 17% of this group. There were no major preoperative strokes in patients with surgery after the age of 7 years, and no poor outcomes were recorded in this group. A major preoperative stroke prior to surgery had adverse impact on the ultimate patient intelligence quotient (IQ) following surgery. All patients operated on after the age of 7 years had a normal or borderline IQ at follow-up examination. PMID- 1607977 TI - Risk factors predicting operable intracranial hematomas in head injury. AB - A study was performed to examine the incidence of operable traumatic intracranial hematomas accompanying head injuries of differing degrees of severity, and to see if factors predicting operable mass lesions could be identified. Logistic analysis was used to identify independent predictors of operable traumatic intracranial hematomas. Data were gathered prospectively on 1039 patients admitted with head injury between January, 1986, and December, 1990. Patient age, Glasgow Coma Scale (GCS) score, pupillary inequality, and injury by falling were all independent predictors of the presence of operable intracranial hematomas (p = 0.0000, 0.0000, 0.0182, and 0.0001, respectively). Injury to vehicle occupants was less likely to result in operable mass lesions (p = 0.0001) than injury by other means. The incidence of traumatic intracranial hematomas in patients over 50 years old was three to four times higher than in those under 30 years of age. Not surprisingly, the incidence of operable hematomas increased with decreasing GCS scores. However, even at a GCS score of 13 to 15, patients with other risk factors had a substantial incidence of operable mass lesions. There was a 29% incidence of operable intracranial hematomas for patients with a GCS score of 13 to 15, aged over 40 years and injured in a fall. It is suggested that patients who are middle-aged or older, or those injured in falls, are at particular risk for traumatic intracranial hematomas even if their GCS score is high. These patients should have early definitive investigation with computerized tomography in order to identify operable hematomas and to initiate surgical treatment prior to neurological deterioration from mass effect. PMID- 1607978 TI - Epidural steroids, postoperative morbidity, and recovery in patients undergoing microsurgical lumbar discectomy. AB - Intraoperative epidural corticosteroids have been used by some surgeons to decrease pain following surgery for a herniated lumbar disc. In this study, 84 consecutively treated, comparable patients with unilateral lumbar disc herniation were prospectively assigned randomly to receive either epidural corticosteroids (40 mg methylprednisolone acetate) or saline at the conclusion of the operative procedure. The postoperative morbidity of these two groups was evaluated by tabulating the following parameters: pain relief as measured by consumption of postoperative pain medications; the length of hospital stay; postoperative functional status; and the time interval from surgery until return to work. The mean postoperative analgesic medications consumed was 12.2 +/- 1.9 mg of morphine equivalents in the corticosteroid group versus 12.2 +/- 1.8 mg of morphine equivalents in the control group. The mean hospital stay was less than 2 days in each group, and the mean interval until return to work was 21.2 +/- 2.7 days in the corticosteroid group versus 25.4 +/- 3.1 days in the control group. Moreover, no statistically significant difference was measured between the steroid-treated and control groups when the data were stratified for sex, age, and site of disc herniation. The mean outcome scores, which are derived from a postoperative assessment of pain relief resulting from surgery, functional status, and interval until return to work, were identical in the corticosteroid and control groups. This study concludes that epidural corticosteroid administration after microsurgical lumbar discectomy for unilateral disc herniation does not lessen postoperative morbidity or improve functional recovery. PMID- 1607979 TI - The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. AB - Plasma and cerebrospinal fluid (CSF) endothelin (ET)-1-like immunoactivity in 27 patients with aneurysmal subarachnoid hemorrhage (SAH) was measured serially by radioimmunoassay for 2 weeks after SAH onset. Mean ET-1-like immunoactivity levels in plasma of patients with SAH were highly elevated during the whole study period, while the levels in CSF of the same patients were not. Plasma ET-1-like immunoactivity levels in patients with SAH classified as Fisher computerized tomography (CT) Group 3 were higher than those in patients with SAH classified as Fisher CT Groups 1 and 2. There were no significant differences in plasma ET-1 like immunoactivity levels between the patient groups stratified by Hunt and Kosnik grade. In this series, plasma ET-1-like immunoactivity levels in the 12 patients with vasospasm were higher than those in the 15 patients without vasospasm during the 1st week; CSF ET-1-like immunoactivity levels in patients with vasospasm were in the normal range on Days 0 to 3 after SAH onset, then became elevated on Days 5 to 7 and remained high until the end of the 2nd week. In contrast, CSF ET-1-like immunoactivity levels in patients without vasospasm were within the normal range during the entire period of study. The time course of the occurrence of vasospasm and that of the increase in CSF ET-1-like immunoactivity coincided precisely. The possible role of endogenous ET-1 in the pathogenesis of vasospasm due to SAH is discussed. PMID- 1607980 TI - Expectant fathers' roles during labor and birth. AB - OBJECTIVE: To describe and explain the expectant father's experience during labor and delivery. DESIGN: A grounded theory methodology was used for data collection and analysis. SETTING: Semistructured interviews were held in the homes of participants, and data were collected from observations in the labor and delivery rooms. PARTICIPANTS: Twenty couples recruited from five hospitals in the San Francisco Bay area. MAIN OUTCOMES: The study identified three roles that expectant fathers adopted: coach, teammate, and witness. RESULTS: The roles adopted by expectant fathers were related to the degrees of understanding and mutuality within the couples' relationships. The majority of the men in the study adopted the role of witness. CONCLUSION: The current expectations of the father in the role of coach should be reevaluated. PMID- 1607981 TI - Antepartum home-care services for high-risk women. AB - OBJECTIVE: To determine the scope of home-care services for pregnant women by addressing types of agencies, nursing personnel, and problems encountered. DESIGN: Descriptive study with survey questionnaire. SETTING: A sample of urban and rural settings throughout Minnesota. PARTICIPANTS: Nine private and 38 public agencies providing antepartum home-care services. MAIN OUTCOME: Data described clients, agencies, personnel, and services. RESULTS: Differences were reflected in the nursing skills and interventions used with high-risk pregnant women. Public agencies identified teenage pregnancy as the most frequent antepartum problem, while private agencies identified preterm labor. CONCLUSION: Results suggest a need to examine the scope of antepartum home-care services. PMID- 1607982 TI - Mothers' and nurses' perceptions of the needs of women experiencing preterm labor. AB - OBJECTIVE: To describe and compare mothers' and nurses' perceptions of the needs of women experiencing preterm labor. DESIGN: A descriptive/comparative approach was used. SETTING: A tertiary-care teaching facility. PARTICIPANTS: Convenience sample of 14 postpartum mothers and 25 registered nurses. MAIN OUTCOMES: Subjects responded to 56 statements about the needs of women in preterm labor. RESULTS: No statistically significant differences were found between mothers and nurses in their total responses to questionnaire items, but some significant isolated differences existed. CONCLUSION: The nurse who identifies and satisfies these needs is likely to be more effective in meeting nursing-care goals. PMID- 1607984 TI - The feminization of AIDS. PMID- 1607983 TI - Breast self-examination. PMID- 1607985 TI - HIV disease and pregnancy. Part 1. Epidemiology, pathogenesis, and natural history. AB - Women constitute the fastest growing component of the human immunodeficiency virus (HIV) epidemic. The majority of women with HIV disease are of reproductive age, and perinatally acquired HIV infection has increased proportionately. The nurse needs knowledge about the unique interactions between HIV infection and pregnancy to provide the complex care required during the perinatal period. An overview of the epidemiology, pathogenesis, and natural history of HIV disease focusing on women is presented. The effects of pregnancy on the progression of HIV disease and the effects of HIV disease on pregnancy outcomes are explored. PMID- 1607987 TI - Effect of pattern adaptation on spatial frequency discrimination. AB - The effect of pattern adaptation on spatial frequency discrimination was examined in two experiments. In the first experiment delta f/f was measured (with and without adaptation) as a function of stimulus contrast; in the second experiment the contrast required to discriminate a fixed delta f/f was measured (with and without adaptation) as a function of the value of delta f/f. Maximum precision, as measured by the asymptotic value that delta f/f approaches at medium and high contrasts, was not altered by adaptation. Rather, the effect of adaptation was to translate the functions relating delta f/f and contrast along the log-contrast axis, i.e., to increase by a constant factor the contrast required to achieve a given precision of discrimination. This factor agreed closely with the factor by which adaptation raised the contrast threshold for detection of the test stimuli. The largest effects were observed when the reference and the adapting stimuli had the same spatial frequency (5 cycles/deg). Smaller or negligible effects were observed when reference and adapting frequencies differed by an octave. PMID- 1607986 TI - HIV disease and pregnancy. Part 2. Antepartum and intrapartum care. AB - The spread of human immunodeficiency virus (HIV) disease among childbearing women presents a unique nursing challenge in the delivery of specialized antepartum and intrapartum care. The nurse must be competent in the delivery of psychosocial and physical care to these women, as well as assume a pivotal role as a member of the multidisciplinary health-care team. Aspects of care, from the diagnosis of pregnancy through delivery of the neonate, that are unique to women with HIV disease are described. PMID- 1607988 TI - Immobility of some second-order stimuli in human peripheral vision. AB - Real-world objects and events are often demarcated and defined by changes of luminance. Such stimuli are easily noticed by human beings whether the stimuli occur in central or in peripheral vision. It is also possible to use differences of color, texture, contrast, or temporal characteristics to create visual stimuli (so-called non-luminance-domain or second-order stimuli). Here I report the discovery that a variety of spatially periodic, second-order patterns, when set in motion in peripheral vision, appear stationary even though their structure is clearly visible. The immobility of the second-order stimuli is evidenced by the striking inability of observers to report their direction of motion. Special signal transformations are required to reveal the motion of second-order stimuli to higher-stage motion mechanisms, and the immobility of second-order stimuli in peripheral but not in central vision suggests that the processing of the transformed signals by higher-stage motion mechanisms changes radically from central to peripheral vision. PMID- 1607989 TI - Stereopsis at isoluminance in the absence of chromatic aberrations. AB - Stereo (front-back) discrimination thresholds were measured in a two-interval forced-choice paradigm for chromatic (red-green) random-dot stereograms that had all detectable longitudinal and transverse aberrations removed by low-pass filtering. The thresholds were measured as a function of the luminance ratio of the red and the green stereo elements. Although individual differences were apparent, three subjects were able to fuse all the stimuli, including those at isoluminance. A quantitative, ideal-observer analysis was used to determine the neural efficiency with which color and luminance information was used in this stereo task. For two subjects, efficiency was constant as a function of the red to-green ratio; for the third subject, efficiency was less near isoluminance. PMID- 1607990 TI - Chromatic and luminance signals in visual memory. AB - The efficiency of chromatic and luminance signals was studied in a set of tasks requiring the discrimination of two colors. Discrimination was measured around an adapting achromatic light and a number of other points in a three-dimensional color space. As a baseline, discrimination thresholds were measured under conditions permitting a side-by-side comparison of stimuli in space or time. For the spatiotemporal configurations used in these experiments, chromatic signals were more efficient than luminance signals in terms of the difference in cone excitation required at the discrimination threshold. When stimuli were separated in both space and time, so that memory was required for their comparison, the efficiency of luminance signals was attenuated further, while chromatic signals retained their efficiency. Further experiments showed that the addition of a memory requirement did not impair the accuracy of luminance discrimination when the two test colors could be placed in distinct perceptual categories with respect to the surround color. Our results indicate that chromatic signals are particularly efficient in simple color discrimination tasks requiring even the barest amount of memory, especially when the perceptual categorization scheme is not available for the comparison of stimuli. PMID- 1607991 TI - Three-dimensional imaging utilizing energy discrimination. II. AB - A new algorithm for three-dimensional image reconstruction in nuclear medicine in which scattered radiation rather than multiple projected images is used for determination of the source depth within the body is proposed. Images taken from numerous energy windows are combined for the reconstruction of the source distribution in the body. In the first paper of this series Gunter et al. [IEEE Trans. Nucl. Sci. 37, 1300 (1990)] examined simple linear algorithms for recovering source depth information from scattered radiation. These linear algorithms were unsuccessful because the scattering process produces little signal in the low-energy images at high spatial frequencies. As a result, the reconstructed source distributions exhibited nodal patterns and blurring. The scattering kernel that was measured and reported in the first paper is now examined more carefully. The singular-value decomposition of the kernel matrices is used to break the reconstruction problem into distinct channels that relate energy spectra to source depth distributions. Based on this analysis, a new nonlinear reconstruction algorithm that avoids the earlier problems is proposed. The new algorithm does not degrade spatial resolution in the imaging plane and provides depth resolution with a standard deviation of 4 cm for point sources without requiring any camera motion. The algorithm also provides significant attenuation correction and, therefore, improved quantitation of the source distribution. PMID- 1607993 TI - Modification of the maxillary Le Fort I osteotomy in cleft-orthognathic surgery: the unilateral cleft lip and palate deformity. AB - Modifications of the Le Fort I osteotomy are described that allow for the simultaneous routine and safe management of maxillary hypoplasia, residual oronasal fistula, bony defects, soft-tissue scarring, and cleft-dental gap in adolescents with unilateral cleft lip and palate (UCLP). The results of this operation with 40 consecutive patients are presented, together with follow-up findings ranging from 15 months to 4 years 5 months. Parameters reviewed include cleft-dental gap closure, maintenance of attached gingiva at the cleft site, maintenance of a positive overjet and overbite, closure of residual oronasal fistula, the need for prosthetics to complete dental rehabilitation, and surgical morbidity. Thirteen of the patients also underwent simultaneous sagittal split osteotomies of the mandible, and 29 had a genioplasty performed. In 32 of the patients surgical cleft-dental gap closure was planned, and was successfully executed in all but one. Thirty-seven patients underwent successful simultaneous oronasal fistula closure, but in three cases, small residual fistulas remained. In all cases, attached gingiva was maintained in the region of the cleft site and along the tooth-bearing surfaces. Almost all of the patients maintained a positive overjet (39 of 40) and 85% maintained a positive (34 of 40) or at least neutral (4 of 10) overbite. Complications were few and generally not serious. PMID- 1607992 TI - Parameters of care--92. PMID- 1607994 TI - Developmental significance of delayed closure of the mandibular symphysis. AB - The unique finding of a midline suture at the mandibular symphysis in cleidocranial dysplasia is presented and discussed in regard to its relation to facial skeletal development. PMID- 1607995 TI - Cranial base morphology in cleft lip and palate: a cephalometric study from 7 to 18 years of age. AB - Four cleft lip/palate groups were cephalometrically compared with a noncleft control group using three cranial base dimensions: anterior (ACB) and posterior (PCB) cranial base, and cranial base angle (CBa). The groups were compared by age from 7 to 18 years. The results showed that the cleft lip and/or alveolus group was not different from the control group in the three dimensions. Unilateral and bilateral cleft lip and palate and isolated cleft palate cases were generally shorter in ACB and PCB for most of the growth period, particularly after age 8 to 9 years. The cranial base angle remained similar for all the cleft groups when compared with the noncleft group. These findings support the view that intrinsic tissue defects or errors during embryologic development may result in basicranial abnormalities and orofacial clefting. PMID- 1607996 TI - Cost of a genioplasty under deep intravenous sedation in a private office versus general anesthesia in an outpatient surgical center. AB - The cases of twenty-four patients who underwent genioplasties either under deep intravenous (IV) sedation in a dental office or under general anesthesia in a surgical center were reviewed. A cost comparison of this operation in these two environments showed that it was twice as expensive to have the same procedure done in an outpatient surgical suite under general anesthesia as it was in a private office under IV sedation. PMID- 1607997 TI - Morbidity and mortality from pharmacosedation and general anesthesia in the dental office. AB - Morbidity and mortality (M&M) statistics have been used to determine the safety of pharmacosedation and general anesthesia for dental procedures. Although relevant, these data often do not describe what actually caused the problems. Descriptive data are needed to understand etiologic factors and to accurately set malpractice insurance rates, establish legislative regulations, and determine means of prevention. The purpose of this study was to characterize the factors involved in causing M&M in a national data base of dental patients who received either pharmacosedation or general anesthesia. Letters were sent to all state dental boards requesting detailed information on cases associated with M&M during the last 15 years. Follow-up letters and telephone contacts were made with noncompliant boards. Forty-three cases were reported from nine states, with mortality comprising 81.4% of the cases. The mean patient age was 18 years, with a range from 2 to 42 years. Seventy-five percent of the cases were classified as American Society of Anesthesiologists (ASA) class I, 21% as ASA II, and 4% as ASA III. The mean number of pharmacological agents used was three, with a range from one to seven. In 32% of the cases heart rate was monitored, in 23% respiration was monitored, in 23% blood pressure was monitored, in 8% tissue oxygen saturation was monitored, and in 4% heart rhythm was monitored. Fifty-nine percent of the practitioners performed basic life support as a part of resuscitative efforts, 21% performed some measure of advanced cardiac life support, and in 45% of the cases narcotic reversal was attempted.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1607999 TI - Correlation between pain and dysfunction and intra-articular adhesions in patients with internal derangement of the temporomandibular joint. AB - The correlation between pain and dysfunction scores obtained by questionnaire and an adhesions index obtained via arthroscopic inspection was investigated in 28 patients with internal derangements (closed lock) of the temporomandibular joint (TMJ). A weak correlation was found between pain scores and the adhesions index. However, joint noise had a negative correlation with both severity and distribution of adhesions in the TMJ. A weak, but statistically significant, negative correlation also was found between the degree of interincisal opening and the adhesions index. This study indicates that intra-articular adhesions are one of the factors contributing to limited mouth opening in patients with closed lock, but that they do not cause TMJ pain. PMID- 1607998 TI - Morbidity and mortality with outpatient anesthesia: the Massachusetts experience. AB - All 147 active members of the Massachusetts Society of Oral and Maxillofacial Surgeons responded to an anesthesia survey. They had treated 416,561 patients during 1989. This article reports the results of the survey and specific untoward anesthetic events as recalled by these practitioners. Use of various anesthetic agents in 1989 and 1984 are compared. PMID- 1608000 TI - A light and electron microscopic comparison of osseointegration of six implant types. AB - This study compared six commercially available implants placed in an animal model for 5 months. Twelve of the implants were used for light microscopic analysis, and the remaining 12 were used for scanning electron microscopic analysis. With the exception of one implant, newly formed bone was evident in direct apposition to portions of all control implants. The light microscopic and scanning electron microscopic evaluations of the tissues surrounding the six commercially available implant types indicated that initial osseointegration is likely with all types. Implant design, material, and submergibility do not appear to be essential for initial osseointegration to occur as long as a biocompatible material is selected and the implant is placed using minimally traumatic surgical techniques. PMID- 1608001 TI - Osseous healing of the sagittal ramus osteotomy: a histologic comparison of rigid and nonrigid fixation in Macaca mulatta. AB - Twenty-three adult female rhesus monkeys underwent advancement of the mandible by the sagittal split ramus osteotomy. Twelve had the proximal and distal segments wired together and underwent 6 weeks of maxillomandibular fixation (MMF). Eleven animals had bicortical bone screws placed between the segments and no postsurgical MMF. The animals were killed at 6 and 12 weeks and the osteotomy sites were prepared for histologic examination. Overall, the results showed that the two groups of animals underwent markedly different patterns of osseous healing. The osteotomy sites in the MMF animals were filled with callus, which then formed bone. In contrast, no callus was found in the majority of the rigid fixation osteotomy sites; direct bony deposition was found instead. The results of this investigation show that, like long bones, the sagittal osteotomy can heal by direct or indirect means depending on the rigidity of the fixation. PMID- 1608002 TI - Circulatory and respiratory effects of lidocaine administered into the rat maxillofacial circulation. AB - The inadvertent intra-arterial administration of local anesthetics is a serious hazard of oral operations. For this reason, the circulatory and respiratory consequences of introducing lidocaine into the maxillofacial (MF) arterial circulation were examined in anesthetized rats. Lidocaine boluses of 0.3 to 6.0 mg/kg increased infusion pressure (IP) by up to 85%, signifying considerable local vasoconstriction; following a 6.0 mg/kg injection, heart rate (HR) remained unaffected, mean blood pressure (BP) increased by 5%, and respiratory rate (RR) decreased by 20%. Infusions of 50 or 150 micrograms/kg/min for 30 minutes had no effect on the preceding parameters, but within 15 minutes of infusing lidocaine at 600 micrograms/kg/min, IP increased by 97% and RR decreased by 31%; BP and HR remained unaffected. It was concluded that the main consequences of administering plain lidocaine at the aforementioned doses into the rat MF arterial bed were considerable local vasoconstriction and a large reduction in respiratory rate. Heart rate remained unaffected by lidocaine; neither it nor blood pressure is a reliable indicator of approaching systemic toxicity. PMID- 1608003 TI - Diagnostic significance of nuclear DNA content and nuclear area in oral hyperplasia, dysplasia, and carcinoma. AB - The nuclear DNA content and the nuclear area in hyperplasia, dysplasia, and carcinoma of the oral cavity were quantitatively analyzed by microspectrophotometry. In carcinoma, marked variability of the nuclear DNA content and the nuclear area was found. The mean nuclear DNA content, the variance of the nuclear DNA content, the frequency of cells above tetraploid (4 C), the mean nuclear area, and the variance of nuclear area in hyperplasia and dysplasia were significantly different from these values with carcinoma. In some cases of leukoplakia and verrucous hyperplasia with subsequent malignant formation, the values were beyond the lower limit of carcinoma. The results suggest that the nuclear DNA and the nuclear area are important objective indices for predicting malignant potential of precancerous lesions. PMID- 1608004 TI - Well-circumscribed mass of the lateral floor of the mouth. PMID- 1608006 TI - Lymphoma of the paranasal sinuses presenting as cavernous sinus syndrome. PMID- 1608005 TI - Pediatric arthroscopic surgery: a case report with special surgical considerations. PMID- 1608007 TI - Congenital extraoral fistula from an auxiliary parotid gland. AB - A rare case of an auxiliary major salivary gland in the parotid region with an external fistula is reported. Clinical findings and management are described, and relevant embryology and etiology are discussed. PMID- 1608008 TI - Cryptococcosis as an exclusive oral presentation. PMID- 1608009 TI - Chondrosarcoma and osteosarcoma arising in polyostotic fibrous dysplasia. PMID- 1608010 TI - Fabrication of a facial orthotic for protection of a fractured nose. PMID- 1608011 TI - Maintaining the diversity of our specialty. PMID- 1608012 TI - Nursing management of autologous blood transfusion. AB - Autologous blood transfusion (ATS) is now a common procedure used in a variety of health care settings. ATS can occur during several stages in a patient's care and may be administered through a variety of methods. This article discusses the development of ATS, its advantages and disadvantages, issues surrounding its use, and the types of ATS currently in use. Examples of several methods and nursing considerations for management of ATS are presented. PMID- 1608013 TI - Current trends in blood component therapy: the evolution of a safer, more effective product. AB - Current trends in blood component therapy have focused on providing the safest, most effective means for transfusion therapy. During the last decade a reassessment of the indications for transfusion of the various blood components has occurred, mainly because of the increased awareness of the risks associated with the administration of blood components such as disease transmission and alloimmunization. Concerns regarding the risks inherent in blood transfusions have stimulated advances in technologies to prepare and deliver blood components along with the development of alternative pharmacologic approaches to the actual administration of blood products. PMID- 1608014 TI - Peripherally inserted central catheters. Guidewire versus nonguidewire use: a comparative study. AB - To date, no research articles have been published that explore the practice of using guidewires for placement of peripherally inserted central catheters. The literature contains speculations regarding the pros and cons of guidewire use. However, no studies to date have compared patient outcomes when peripherally inserted central catheter lines are inserted with and without guidewires. To examine the use of guidewires for peripherally inserted central lines, a comparative study was conducted at two acute care facilities, one using guidewires for insertion and one inserting peripherally inserted central catheter lines without guidewires. 109 catheters were studied between January 1, 1990 and January 1, 1991. The primary focus of this study was to examine whether guidewire use places patients at higher risk for catheter-related complications, particularly phlebitis. No significant differences in phlebitis rates between the two study sites were found. Other catheter-related and noncatheter-related complications were similar between the two facilities. The results of this study do not support the belief that guidewire use increases complication rates. PMID- 1608015 TI - Intermittent heparin flushing protocols. A standardization issue. AB - The intermittent intravenous lock is an expedient method for accomplishing periodic I.V. procedures. Unfortunately, the heparinized saline solution used to flush these catheters has not been standardized to any acceptable degree. In response to this lack of standardization, a nationwide survey was conducted to obtain a consensus that might lead to a recommendation of standards for heparin flushing protocols. This article presents the results of the survey and reviews literature regarding current flushing protocols. PMID- 1608016 TI - Understanding Crohn's disease. AB - Knowledge about Crohn's disease is limited and many misconceptions about the disease continue to exist. After many years of research the cause and the cure of Crohn's disease remain unknown. This article provides an overview of the disease, treatment modalities, and nursing interventions to implement for the patient with Crohn's disease. PMID- 1608017 TI - A hospital CEO's perspective of the importance of certification. PMID- 1608018 TI - Renal arterial Resistance Index in pregnant and nonpregnant women: evaluation with color and pulse Doppler ultrasound. AB - The Resistance Index (RI) was studied in the main renal arteries in normal nonpregnant women and its change during normal pregnancy. One hundred and seventy color and pulse Doppler sonographic examinations were performed on 31 nonpregnant and 54 pregnant women. The range of gestation was 5-39 weeks, and patients divided into three groups; 5-12, 13-25 and 26-39 weeks of pregnancy, respectively. The RI was calculated in both main renal arteries. In nonpregnant women the left main renal artery RI mean = 0.587 +/- 0.021, and the right main renal artery RI mean = 0.584 +/- 0.028. In pregnant women the left main renal artery RI mean was 0.681 +/- 0.029, and the right main renal artery RI mean was 0.697 +/- 0.034. There was a significant difference between the main renal artery RI in pregnant and nonpregnant women (P less than 0.01). There was no significant difference between left and right main renal artery in pregnant and nonpregnant women (P less than 0.01). There was no correlation between gestational age and RI in the right main renal artery but a statistically significant correlation with gestational age in the left main renal artery (P less than 0.05). PMID- 1608019 TI - Cerebral lipid peroxidation in the growth retarded rat fetus under normoxia and hypoxia. AB - To detect a possible relationship between the increased vulnerability of the brain of the growth retarded fetus and lipid peroxidation, the activity of the latter was investigated in the forebrain of rat fetuses on day 22 of gestation (term = 23). Growth retardation was induced by uterine artery ligation on day 18. The susceptibility of the forebrain to lipid peroxidation was analysed using the thiobarbituric acid technique after exposure of the awake dams to room air or hypoxia (10% O2) for 58 minutes. Hemodynamics and blood gas status in the dams were stable under conditions of normoxia. When exposed to hypoxia, oxygen availability decreased and blood pressure fell slightly. When normalised for litter, lipid peroxidation covaried with fetal weight in fetuses from normoxic dams, only when Fe2+ (a promotor of lipid peroxidation) was added in the incubation. In fetuses from hypoxic dams, this relationship existed irrespective of whether Fe2+ was present during incubation. In all of these associations, smaller fetuses exhibited more intense lipid peroxidation. In the perinatal period, an increased vulnerability of the central nervous system prevails in growth retarded individuals. An increased tendency to undergo lipid peroxidation and/or a weak defence against this process may be part of the pathophysiologic background. PMID- 1608020 TI - Short-term outcome in infants with birth weights less than 1750 g born to mothers with HELLP syndrome. AB - Premature infants born to mothers with HELLP syndrome were reported to have a less favourable outcome compared to infants with uncomplicated maternal history. We investigated the short term outcome in 21 premature infants with birth weights less than 1750 g born to mothers with HELLP syndrome. Median birth weight was 1050 g (range 420 g-1750 g), corresponding gestational age 29 weeks (range 26-35 weeks). Mechanical ventilation for RDS was necessary in 15 infants. Intracranial hemorrhage was diagnosed in 2 infants, 1 of the surviving infants developed bronchopulmonary dysplasia. Acute renal failure was observed in 3 infants immediately after birth. Mortality was attributed to progressive respiratory failure in 2 patients (b.w. 420 g and 490 g) and persisting acute renal failure in 1 patient (b.w. 520 g) Leucocytopenia (less than 9000/mm3) was observed in 13 infants and thrombocytopenia (less than 115000/mm3) was noted in 4 infants during the first day. Eighteen infants survived. We conclude, that the short term outcome in infants born to mothers with HELLP syndrome is not as poor, as previously reported. PMID- 1608021 TI - Prediction of fetal outcome in small for gestational age fetuses: comparison of Doppler measurements obtained from different fetal vessels. AB - Blood flow velocity waveforms were recorded from different vascular districts including umbilical artery, descending aorta, renal artery, internal carotid artery and middle cerebral artery in a population of 120 small for gestational age fetuses free from structural and chromosomal abnormalities. The pulsatility index from each vessel as well as the ratios between the pulsatility indices from peripheral and cerebral vessels were calculated and related to perinatal outcome. The pulsatility index of middle cerebral artery resulted the most efficient measurement to predict the development of perinatal adverse outcome when each vessel was considered singularly, however, better results were achieved when the ratios between pulsatility indices were related to perinatal outcome; this is mot evident for the ratio between the pulsatility indices of umbilical artery and middle cerebral artery. Our results suggest the usefulness of this ratio in differentiating small for gestational age fetuses at risk of unfavorable outcome. PMID- 1608022 TI - The effect of heparin in arterial catheters on the coagulation in preterm infants. AB - The coagulation of 16 healthy preterm infants (control infants) was compared with 15 ventilated preterm infants (study infants) receiving 0.5 ml/hr of a solution containing 5 IU/ml heparin intra-arterially in order to keep a radial artery catheter patent. A venous sample was obtained in both groups, in the study group a sample from the arterial catheter was also taken. Both the heparin dependent (APTT, thrombin time) and the heparin independent coagulation factors (AT-III, Clotting Factors I, II, V and VII) were not different between the venous samples of both groups. The arterial samples showed a significantly elevated APTT and thrombin time compared with venous samples, especially when the heparin level in the sample was higher than 0.1 IU/ml. These elevations are due to heparin in the sample from the arterial line as the venous sample in the same patient did not show any heparin effect. The heparin non-dependent factors were not different between venous and arterial samples. We conclude that a solution containing 5 IU/ml heparin given at a rate of 0.5 ml/hr does not influence coagulation in preterm infants. Determination of heparin independent coagulation factors can be done in both venous samples and samples taken from the arterial catheter, in these arterial samples the heparin dependent factors can be influenced by the heparin present in the catheters. PMID- 1608023 TI - Glucose, insulin, HGH and IGF-I levels in maternal serum, amniotic fluid and umbilical venous serum: a comparison between late normal pregnancy and pregnancies complicated with diabetes and fetal growth retardation. AB - Fetal growth and development is dependent upon various growth factors such as glucose, insulin, HGH and IGF-I. These growth factors were measured in maternal serum (MS), amniotic fluid (AF) and umbilical venous serum (UV) in late gestation in normal, insulin dependent diabetic pregnancies (IDDM) and in pregnancies complicated with intrauterine growth retardation (IUGR). The UV glucose values of 1.9 +/- 0.9 mmol/L and UV insulin values of 8.0 +/- 1.8 mU/L were the lowest in IUGR pregnancies, and the highest were in UV serum from IDDM pregnancies, and the difference was statistically significant for this two groups. IGF-I values in UV indicated that there was significant difference in IGF-I concentrations when both, IUGR and IDDM groups were compared to the controls. There was a parallel shift in AF and MS glucose and insulin concentration as birthweight increased. The highest IGF-I values of 7.2 +/- 9.6 mumol/L in AF and MS were found in pregnancies with infants whose birthweight was 3500 grams and greater. Infants from pregnancies complicated with IUGR and IGF-I low values of 0.6 +/- 1.2 mumol/L in AF. HGH concentrations of 15.6 +/- 9.4 micrograms/L in UV were observed in IDDM pregnancies and significantly lower than the values in IUGR and normal pregnancies. HGH umbilical venous values decreased with duration of pregnancy and with increase in fetal size. The high HGH concentrations in the fetus and its dramatic fall after parturition, and the obtained negative correlation between HGH and IGF-I in umbilical vein may exhibit the maturation of the hypothalamic-growth hormone-IGF-I axis. It seems likely that changes in maternal serum, umbilical venous and amniotic fluid insulin-like growth factor I influence birthweight in normal and IUGR infants and in those of diabetic mothers. PMID- 1608024 TI - Elevation of prostaglandin levels in pregnancies complicated by premature rupture of the membranes. AB - Premature labour and infection (both maternal and neonatal) are common outcomes of pregnancies complicated by premature rupture of the membranes (PROM). Both conditions are associated with elevation of prostaglandin levels. It therefore seems likely that prostaglandins may be increased in patients with pregnancies complicated by PROM. The aim of this study was to test this hypothesis by comparing prostaglandin levels in pregnancies complicated by PROM to those from control pregnancies with intact membranes. Paired fetal and maternal samples were obtained from nine patients with pregnancies complicated by PROM. The median onset of PROM was 28 weeks (range 22-31 weeks). Fetal blood was obtained by cordocentesis, ultrasound guided puncture of the umbilical cord and this was performed at a median of 4 days (range 1-28) following rupture of the membranes. Delivery occurred at a median gestational age of 33 weeks (range 28-37). Paired samples were also obtained from 12 "control" pregnancies with intact membranes and no evidence of infection or premature labour. The indications for cordocentesis in this group were rapid fetal karyotyping following the ultrasonic detection of small fetal structural abnormalities or fetal blood grouping following the detection of high maternal haemolytic antibody titre. Sampling was performed at a median of 27 weeks of gestation (range 22-32). Prostaglandin levels were assessed by determination of the level of the metabolic compound bicyclo-PGEM by radioimmunoassay.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608025 TI - Brainstem conduction time abnormalities in small for gestational age infants. AB - Brainstem auditory evoked responses (BAER) were recorded in 89 neonates born between 32 and 40 weeks, in order to analyze the consequences of intrauterine growth retardation on brainstem conduction time. The I-V interval was measured in 28 appropriate for gestational age (AGA) infants (control group), in 24 small for gestational age (SGA) infants with maternal hypertensive disease (MHD) and in 37 SGA infants without MHD. At any gestational age, SGA infants with MHD always presented an acceleration of their brainstem conduction time as compared to the other SGA infants. For the SGA full-term twins without MHD, the brainstem conduction time was delayed. These results reflect the specific consequences on brainstem development of the various factors responsible for intrauterine growth retardation (IURG). PMID- 1608026 TI - Phosphatidylglycerol determination in the amniotic fluid from a PAD placed over the vulva: a method for diagnosis of fetal lung maturity in cases of premature ruptured membranes. AB - Four hundred and forty seven pregnant women with ruptured membranes, were prospectively studied in order to assess the diagnostic capacity of Phosphatidylglycerol (PhG) determination in amniotic fluid recovered from vulval pads in the diagnosis of Hyaline Membrane Disease (HMD). The identification of PhG was performed using one dimensional silica gel thin layer chromatography. The sensitivity of PhG determination in the diagnosis of HMD in newborns of the total population was found to be 88.2%, with a specificity of 76.9%. In the study population, the incidence of HMD was 7.6%, the negative predictive value was 98.8% and, the positive predictive value was 24.0%. When the 265 newborns of the gestational age group of less than or equal to 34 weeks is considered, we observed an incidence of HMD of 12.1%. The diagnostic capacity of PhG in this group was shown by a sensitivity of 87.5%, a specificity of 76.4%, a positive predictive value of 33.7% and a negative predictive value of 97.8%. This method of assessment of fetal lung maturity has a diagnostic capability similar to that described by other authors, who used amniotic fluid obtained vaginally or transabdominally. The procedure described here of amniotic fluid collection is non-invasive, harmless to the mother and fetus and simple to perform. The characteristics of this method, allow serial studies of the amniotic fluid to be carried out. PMID- 1608027 TI - Influence of increasing postnatal age on respiratory timing and reflex activity in preterm ventilated infants. AB - The influence of postnatal age on spontaneous respiratory time, measured both on and off continuous positive airways pressure (CPAP), and the occurrence of the Hering Breuer reflex has been investigated. Consecutive ventilated infants were recruited and only studied when making respiratory efforts during mechanical ventilation. Fifty-three infants were studied on 119 occasions, their median gestational age was 29 weeks and birthweight 1142 gms. All the infants were initially ventilated for the respiratory distress syndrome. Inspiratory and expiratory times were measured from simultaneous flow and oesophageal pressure recordings during a 20-second period of disconnection and during a similar period on 3 cmH2O CPAP. Prolongation of the inspiratory and expiratory time on CPAP compared to that measured during disconnection of more than 10% was evidence of the Hering Breuer reflex. No significant change in the inspiratory or expiratory time either on or off CPAP was noted either between days 1 to 5 or weeks 1 to 4. Both inspiratory and expiratory time tended to be longer on CPAP than during disconnection and these differences reached significance on days 1 and 2 and weeks 1 and 2. No influence of postnatal age was demonstrated on the proportion of infants in whom the Hering Breuer reflex was demonstrated. Our results suggest that, during the neonatal period, there is no influence of postnatal age on respiratory timings or reflex activity amongst ventilated infants who make spontaneous respiratory efforts during ventilation. These results have important implications regarding the optimum rate at which such infants should be ventilated. PMID- 1608028 TI - Fetal and neonatal cerebral circulation: a pulsed Doppler study. AB - We studied the relation between the fetal cerebral circulation and changes in the cerebral circulation directly after birth. With a combined real time ultrasound/pulsed Doppler technique flow velocity waveforms from the fetal umbilical- and carotid-circulation were monitored. Pulsatility Index (PI) was computed and the ratio between Umbilical PI and Carotid PI was calculated. Flow velocity waveforms of the cerebral circulation before birth were related to anterior cerebral artery flow velocity waveforms recorded immediately after birth. The study shows that changes in flow velocity waveforms associated with the intra uterine brain-sparing effect are related to poor obstetrical outcome. Furthermore is shown that the brain-sparing effect in the fetal period is associated with higher PI values in the cerebrovascular circulation in the neonatal period. It is suggested that changes in these PI values, representing changes in cerebrovascular resistance, might be indicative of cerebral ischemia in the neonate. PMID- 1608029 TI - Ultrastructural localization of alkaline and acid phosphatase activities in dental plaque. AB - Ultrastructural cytohistochemical techniques showed presence of acid and alkaline phosphatases in dental plaque. Both phosphatases had intra- and extramicrobial localization. In the extracellular matrix, phosphatases were associated with small vesicles of bacterial origin, or were freely scattered in the matrix without apparent connection with microbial structures. Intracellularly, alkaline (AlkP) and acid (AcP) phosphatases were observed in Gram-negative and Gram positive bacteria, showing a different localization. The AlkP was mainly located in the periplasmic space, while AcP had a double preferential localization: along the outer surface of the cell wall and in the periplasmic space. Less frequently an intracellular phosphatase reaction was seen in the cytoplasm. PMID- 1608030 TI - Enhanced collagen phagocytosis by rat molar periodontal fibroblasts after topical application of lipopolysaccharide--ultrastructural observations and morphometric analysis. AB - To investigate the effect of lipopolysaccharide (LPS) on phagocytic activity of collagen fibrils by periodontal fibroblasts, we studied rat molar gingival connective tissue and periodontal ligament under light and electron microscopy after topical application of LPS (5 mg/ml in physiological salt solution (PS)) on the gingival sulcus. Phagocytic activity of collagen fibrils by fibroblasts was evaluated by counting the number of collagen-containing vacuoles inside fibroblasts that were present within a defined area (1200 microns2). Values obtained from fibroblasts in the subepithelial connective tissue, the region near the alveolar crest, and the middle region of periodontal tissue were compared. Periodontal ligament fibroblasts showed increased phagocytosis of the collagen fibrils from 3 hours to 1 day after topical LPS application, but no differences were observed in the gingival tissue. The intracytoplasmic vacuoles containing collagen fibrils were of various sizes and shapes, showing positive for acid phosphatase and/or alkaline phosphatase reaction. Collagen phagocytic activity of the fibroblasts in the middle region of the periodontal ligament also increased after PS treatment. However, this was significantly less than that observed in LPS-treated animals (p less than 0.01). This study indicates that LPS may enhance the degradation of collagen by stimulating the phagocytic activity of the periodontal ligament fibroblasts. PMID- 1608031 TI - Periotest for measuring periodontal characteristics--correlation with periodontal bone loss. AB - The Periotest measures the reaction of the periodontium to a defined percussive force. The percussion is applied to the tooth by an electronically controlled tapping head. Information on structural change is obtained by measurement of both the elastic and viscous characteristics of the periodontium. The latter prevent oscillations of the tooth in the alveolar bone. A value is calculated and is displayed as a "Periotest value". The following research report shows the relation of Periotest values to bone loss. Bone loss was quantitatively determined for 2312 teeth from orthopantomographic radiographs and for 900 teeth exposed to intra-oral films using the standard paralleling technique. A differentiation was made between vertical and horizontal bone loss. Clinical mobility index, pocket depth, gingival recession and papillary hemorrhagic index were also measured. There was a strong association between the Periotest value and bone loss. These results suggest that Periotest evaluation provides an objective indication of the extent of periodontal bone loss. PMID- 1608032 TI - Morphology of neural endings in the human periodontal ligament: an electron microscopic study. AB - The ultrastructure of sensory nerve endings in the human periodontal ligament from 43 extracted teeth was studied using serial sections. Three types of nerve endings were found: free nerve endings (FNE), Ruffini-like endings and lamellated corpuscles. Free nerve endings stem from unmyelinated or from myelinated nerve fibers. The endings contain neurotubuli, neurofilaments and vesicles. Ruffini like receptors were mostly found in the apical part of the periodontal ligament. In these Ruffini-like receptors a particularly abundant concentration of mitochondria appears. In some cases desmosome-like junctions are present between neurite and ensheathing cell. Lamellated corpuscles were also found in the periodontal ligament. The lamellae are extremely endocytotic and are in close contact with each other. PMID- 1608033 TI - Relationship of texture measurements to the prediction of correct evaluations in subtraction radiography. PMID- 1608034 TI - Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss. AB - This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6 fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation. PMID- 1608035 TI - The periodontal differentiation in the phylogeny of teeth--an overview. AB - During the evolution of teeth, different types of periodontal attachment have been developed. On the basis of the comparative histology of periodontal tissues, protoacrodontal, acrodontal, acro-protothecodontal, pleurodontal and thecodontal structures can be distinguished that depend upon the area of attachment (crestal, marginal or socketed type) and the mode of attachment (ankylosis, fibrous or combined type). Due to "phylogenetic memory", changes of the periodontium in health and disease could be interpreted as copies of phylogenetically older patterns. The greatest variations in tooth attachment have originated in acrodont bony fishes and in pleurodont reptiles, whereas the selection for a single thecodont or socketed type was an important event in the evolution of mammals. The detailed structures of cementum, of the fiber apparatus and of the junctional epithelium vary from type to type and within one type. These principal structures are decisive for reaction patterns of degeneration and regeneration. Therefore, comparative periodontology could be an important adjunct to help interpret the natural history of periodontal diseases, to help in the selection of experimental animals and to help provide treatment strategies in both human and veterinary situations. PMID- 1608036 TI - Influence of oral hygiene on elastase concentration of gingival crevicular fluid. AB - PMN elastase concentration of gingival crevicular fluid (GCF) was investigated in 11 healthy volunteers before professional tooth cleaning and after a 5-week period of intensive oral hygiene. GCF was collected using filter paper strips and the enzyme concentration was evaluated by the ELISA-technique. Intensive daily oral hygiene led to a considerable improvement in the clinical indices and to a reduction in the concentration of elastase in GCF. Despite the changes in the oral hygiene status, functional elastase was still present in the samples at the end of the experiment. This could mean that even at clinically healthy sites there is a lack of alpha-1-proteinase inhibitor, the major serum protein inactivating PMN elastase. PMID- 1608037 TI - Nasal absorption of digoxin in rats. AB - The nasal administration of digoxin was studied in rats and compared to intravenous, intraduodenal and rectal administration of the drug. The results indicated that the plasma level of digoxin after nasal administration was comparable to the level after intravenous injection. Administration by the intraduodenal and rectal routes resulted in considerably lower plasma levels. These data reveal that digoxin absorption across the nasal membranes is a reasonable approach. In the in situ nasal and intestinal perfusion experiments, digoxin disappeared from the perfusate following the apparent first-order kinetics. The nasal and intestinal absorption rate of digoxin was reduced by an increase in the perfusion volume. The plot of absorption rate constant against 1/volume resulted in a straight line, suggesting that digoxin is absorbed from nasal mucosa by a passive diffusion process. PMID- 1608039 TI - Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium. AB - We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium. PMID- 1608038 TI - Effects of a new dihydropyridine derivative, FRC-8653, on blood pressure in conscious spontaneously hypertensive rats. AB - Antihypertensive effects of FRC-8653, a new 1,4-dihydropyridine derivative, and its combined effects with an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and a beta-adrenergic blocking agent were examined in conscious spontaneously hypertensive rats (SHR). When administered intravenously to SHR (10, 30 micrograms/kg), FRC-8653 lowered blood pressure more slowly and sustained it longer than nifedipine and nicardipine. Consecutive once-daily administrations of FRC-8653 to SHR (3 mg/kg, p.o.) produced a stable reduction of blood pressure throughout the experimental period of 29 d. When blood pressure was continuously measured for 24 h in conscious unrestricted SHR, orally administered FRC-8653 produced a long-lasting reduction in blood pressure. When concomitantly used with atenolol (30 mg/kg, p.o.), the antihypertensive effect of FRC-8653 was augmented in both potency and duration. However, simultaneous administration of captopril (30 mg/kg, p.o.) or hydrochlorothiazide (2.5 mg/kg, p.o.) did not modify the antihypertensive effect of FRC-8653. PMID- 1608040 TI - [On the drug molecular states dispersed in cyclodextrin matrices]. AB - Molecular states of drug molecules in cyclodextrin solid dispersion systems have been studied. The possibility of inclusion compound formation was investigated between drug and cyclodextrin molecules by grinding, sealed heating and freeze drying. Solid state fluorescent spectroscopic measurements were made on the ground mixtures as well as infrared and photo-acoustic spectroscopies. It was found that time resolved solid state fluorescence analysis was effective to investigate the molecular states of fluorescent probe dispersed in cyclodextrins. Sealed heating of drug-cyclodextrin mixture was recognized as a new unique method for preparing cyclodextrin inclusion compound. In the case of freeze drying, the freezing conditions showed great influences on the drug dispersion states and the crystallinity of the products. The results are explained in terms of the inclusion compound formation by grinding, sealed heating and freeze drying. PMID- 1608041 TI - [Effects of various methanol extracts of crude drugs on experimental subacute and chronic hepatic injury]. AB - The effects of 5 crude drugs (Myricae Cortex, Polygoni Avicularis Herba, Hyperici Erecti Herba, Forsythiae Fructus, Desmodii Herba) on subacute and chronic hepatic injuries induced by carbon tetrachloride (CCl4) or alpha-naphthylisothiocyanate (ANIT) were investigated in rats. All of these crude drugs suppressed significantly the increase of several biochemical parameters with CCl4-injection twice per week for 4 weeks. Polygoni Avicularis Herba and Desmodii Herba among 5 crude drugs also protected the subacute hepatic injury induced by ANIT-injection for 4 weeks. In addition, the therapeutic effect of Desmodii Herba on the chronic hepatic injury induced by CCl4-injection for 9 weeks was recognized. Desmodii Herba has protective effects on the acute and subacute hepatic injuries induced by CCl4 or ANIT and an improving effect on the chronic injury induced by CCl4. Though the increase of hydroxylproline content in the liver began 4 weeks after the CCl4 or ANIT treatment, every crude drug had no significant effect against the liver fibrosis in these study. PMID- 1608042 TI - [Pharmacological study on Naja naja kaouthia Lesson. III. Effects of 50% ethanolic extracts from liver and gall bladder on phagocytic activity of mouse reticuloendothelial system]. AB - Effects of 50% ethanolic extracts from the liver and the gall bladder of Naja naja kaouthia Lesson (COB-L or COB-G) were studied on the phagocytic activity of a mouse reticuloendothelial system. The clearance-rate of carbon was shortened by the oral administration of COB-L or COB-G (50 or 200 mg/kg). COB-L or COB-G promoted the phagocytosis of latex by peritoneal macrophages (M phi). Furthermore, effects of these extracts on the peritoneal M phi were biochemically investigated using in vitro experimental models. The activities of two lysosomal enzymes, acid phosphatase and beta-glucuronidase, and that of lactate dehydrogenase in the peritoneal M phi were enhanced when the M phi were cultured with COB-L or COB-G (10-100 micrograms/ml) for 4 d. In addition, the consumption of glucose in the culture media by the M phi was also enhanced by culturing the media with COB-L or COB-G. When COB-L and COB-G were given orally immediately before and 16 h after the application of picryl chloride (PC) or sheep red blood cell (SRBC), these extracts at a dose of 200 mg/kg did not show any inhibitory effects on the swelling by picryl chloride-inducing contact dermatitis (PC-CD) and by sheep red blood cell delayed type hypersensitivity (SRBC-DTH) in mice. However, these extracts inhibited the immunosuppression with the SRBC 1 x 10(9) cells priming and with the frozen and dried ascites of Ehrlich carcinoma-bearing mice containing immunosupressive substances (EC-sup). These results suggest that COB-L or COB-G biochemically activates the mouse peritoneal M phi, and promotes the phagocytic activity of the M phi and the interaction between M phi and T cell. PMID- 1608043 TI - [Percutaneous absorption of drug from alpha-olefin oligomer gel bases]. AB - The percutaneous absorption of drug from the alpha-olefin oligomer (alpha-OL) gel base prepared by using palmitate of dextrin (Rheopearl KL) as a gelling agent was investigated by using the abdominal skin of rats in vivo. The 20, 30, 40 and 50 alpha-OLs with average molecular weights of 288, 380, 440 and 535, respectively were used in this study. The flurbiprofen (FP) was selected as a model drug. The percutaneous absorption of FP from the alpha-OL gel base was observed to be influenced by the molecular weight of alpha-OL. The percutaneous absorption profiles of FP from 40 and 50 alpha-OLs gel bases were almost the same. On the other hand, the absorption of FP from 30 alpha-OL gel base was significantly higher than those of 40 and 50 alpha-OLs gel bases. Furthermore, the percutaneous absorption of FP from 20 alpha-OL gel base was observed to be the highest in the test gel bases. In order to establish the reason for the differences in the percutaneous absorption of FP from 20, 30, 40 and 50 alpha-OLs gel bases, the apparent partition ratios of FP between water and four different alpha-OLs were determined as a parameter of the affinity of FP for the vehicle. Consequently, it has become apparent that the partition ratio exerts an influence on the percutaneous absorption of FP from the alpha-OL gel bases. PMID- 1608044 TI - [Extra-weak chemiluminescence of drugs. XIV. Quenching effects of anthraquinones on the extra-weak chemiluminescence from lipid peroxidation in rat brain homogenates]. AB - Quenching effects of anthraquinones on the extra-weak chemiluminescence (CL) derived from lipid peroxidation in rat brain homogenates were investigated. Such anthraquinone derivatives as emodin, rhein, and alizarin quenched the CL, while anthraquinone did not quench the CL. A linear relationship between CL-quenching activity and inhibitory rate of malondialdehyde production of various compounds was demonstrated. This technique is useful for the screening method of antioxidants. PMID- 1608045 TI - [Effect of morphological properties on drug release from biodegradable microspheres]. AB - The morphological properties of poly(beta-hydroxybutyric acid) (PHB) or poly(L lactic acid) microspheres loading flomoxef sodium (FMOX) were investigated with regard to FMOX release. The release profiles of FMOX from the microspheres could be divided into two types, a sustained release type and a burst one. Two representative PHB microspheres, the release profiles of which were quite different from those of FMOX, were compared in detail from a morphological point of view. The shapes of their surfaces and sections were observed by using scanning electron microscopy (SEM), and FMOX distribution was analyzed by using electron probe microanalysis. The crystallinity of polymers was further measured by powder X-ray diffratometry. There was little difference in the FMOX distribution and their microscopic properties such as sphere size, specific surface area, shape of surface and section. In contrast, water penetration into the inside of the microspheres was found to be clearly different by use of cryogenic SEM. A significant difference was also observed in the crystallinity of polymers forming the microspheres. The release of FMOX from the microspheres was affected by the crystallinity of polymers forming the microspheres, and burst phenomena occurred in case the polymer was highly crystallized. It was speculated that the crystallization of polymer induced micro voids in the microspheres which functioned as channels for water penetration. PMID- 1608046 TI - Functional morphology of the endomysium in series fibered muscles. AB - Many skeletal muscles, including the feline biceps femoris, are composed of short, tapered myofibers arranged in an overlapping longitudinal series. The endomysium of such muscles transfers tension between overlapping myofibers, and is thus an elastic element in series with them. The endomysium of the cat biceps femoris contains curvilinear collagen fibrils in an approximately isotropic (random) array. The collagen fibrils undergo only a modest reorientation as the myofibers shorten or lengthen within the physiological range. A geometrical model predicts no change in the thickness of the endomysium on changing muscle fiber length and quantifies the expected collagen fibril reorientation in the endomysium as a function of muscle extension. It is also demonstrated that a high proportion of the collagen fibrils will be curvilinear at all sarcomere lengths. The organization of endomysial collagen is appropriate for the transfer of loads between myofibers by means of shear. PMID- 1608047 TI - Revisiting junk DNA. AB - The distribution of functions within genomes of higher organisms relative to processes that lead to the spread of mutations in populations is examined in its general outlines. A number of points are enumerated that collectively put in question the concept of junk DNA: the plausible compatibility of DNA function with rapid substitution rates; the likelihood of superimposed functions along much of eukaryotic DNA; the potential for a merely conditional functionality in sequence repeats; the apparent adoption of macromolecular waste as a strategy for maintaining a function without selective grooming of individual sequence repeats that carry out the function; the likely requirement that any DNA sequence must be "polite" vis-'a-vis (compatible with) functional sequences in its genomic environment; the existence in germ-cell lineages of selective constraints that are not apparent in populations of individuals; and the fact that DNA techtonics the appearance and disappearance of genomic DNA - are not incompatible with function. It is pointed out that the inverse correlation between functional constraints and rates of substitution cannot be claimed to be pillar of the neutral theory, because it is also predicted from a selectionist viewpoint. The dispensability of functional structures is brought into relation with the concept of reproductive sufficiency the survivability of genotypes in the absence of fitter alleles. PMID- 1608048 TI - RAC unanimously approves cancer vaccine trial. PMID- 1608049 TI - Sharks still intrigue cancer researchers. PMID- 1608050 TI - ACS survey finds 9% of cancer patients use questionable treatments. PMID- 1608051 TI - Program exposes minority students to science careers. PMID- 1608052 TI - NIH reauthorization bill leaves Congress, heads for veto. PMID- 1608053 TI - Quality-of-life assessment: patient compliance with questionnaire completion. AB - BACKGROUND: Previous investigators have found that compliance with quality-of life data collection on cancer clinical trials is poor. There is general belief that collecting complete quality-of-life data is at present an unachievable goal. PURPOSE: We assessed the completeness of quality-of-life data collection on trials instituted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), since incorporation of quality-of-life outcomes into trials became mandatory for the group. METHODS: Data from three NCIC CTG trials in which quality of life was a study end point were examined to determine the extent to which protocol specifications were met with respect to questionnaire completion. Two of the studies examined adjuvant therapies, and one examined anti-emetics. In two trials, the quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer was used; in the other, the Breast Cancer Chemotherapy Questionnaire. RESULTS: Patient compliance with questionnaire completion was unexpectedly high: More than 95% of the scheduled questionnaires were returned, and more than 99% of the questions were answered. CONCLUSIONS: We attribute this success to a comprehensive set of measures taken to enhance compliance on these studies. Which of these measures was most contributory requires further investigation, as does the issue of whether similar results can be obtained in other circumstances. IMPLICATIONS: It seems that the commonly held belief that quality-of-life data cannot be successfully collected in multicenter cancer trials is incorrect. PMID- 1608054 TI - Promotion of aberrant crypt foci and cancer in rat colon by thermolyzed protein. AB - BACKGROUND: We have previously shown that thermolyzed protein (casein) cooked with fat in the diet of the rat promotes the growth of aberrant crypt foci (putative precursors of colon cancer) assessed at 100 days. PURPOSE: To determine how thermolysis affects this promotion, we examined thermolysis conditions, quantity of thermolyzed protein in the diet, and duration of thermolysis. To determine whether the previous finding of promotion of aberrant crypt foci corresponds to promotion of cancers assessed much later, we carried out promotion studies until colon cancers appeared. METHODS: F344 rats were given an initiating dose of azoxymethane and were then randomly allocated to groups receiving diets differing in their quantity and quality of casein. The groups were examined for aberrant crypt foci and tumors in the colon. RESULTS: Aberrant crypt foci were promoted by diets containing thermolyzed casein (180 degrees C, 2 hours). Promotion increased with increasing level of thermolyzed casein in the diet (to 20%) and with increasing thermolysis time (to 4 hours). The number of animals with polyps and cancers was higher in the animals receiving thermolyzed protein (2 hours), 16/23 versus 9/26 (P less than .05) and 10/26 versus 3/27 (P less than .05), respectively. The number of aberrant crypts per focus and the number of large aberrant crypt foci were higher in the tumor-bearing animals. CONCLUSIONS: Thermolyzed casein promotes early colonic precursor lesions in a dose-dependent and thermolysis time-dependent manner; thermolyzed casein also promotes colon cancer. IMPLICATIONS: The promoter formed on thermolysis could be involved in colon cancers associated with diets cooked at elevated temperatures, such as can occur with high-fat diets. PMID- 1608055 TI - Incidence of dysplasia and carcinoma of the uterine cervix in an Appalachian population. AB - BACKGROUND: Cervical cancer mortality rates in the Appalachian population of southeastern Kentucky have been shown to be unusually high. To better understand the high cervical cancer death rate in this area, we developed a population-based cervical disease registry. PURPOSE: This study describes the incidence of cervical dysplasia, carcinoma in situ, and invasive cervical cancer in 1986 and 1987 among White women in a 36-county area of Appalachian Kentucky based on histologic diagnoses. METHODS: We compared average annual age-adjusted incidence rates for carcinoma in situ and invasive cervical cancer in the study area with those for women in the Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS: The incidence rate of invasive cervical cancer for women in the study area (14.9 per 100,000) was nearly twice that for White women in the SEER population (7.8 per 100,000), but it was similar to that for Black women in the SEER population (15.3 per 100,000). The incidence of carcinoma in situ for women in the study population (38.2 per 100,000) was 21% higher than that for White women (31.5 per 100,000) or for Black women (31.2 per 100,000) in the SEER population. The average annual age-adjusted incidence rate for all grades of dysplasia among women in the study population was 194.6 per 100,000. No comparable population-based incidence rates for dysplasia could be identified. CONCLUSIONS: Cervical cancer incidence rates are higher in Appalachian Kentucky than in the SEER population. Poverty appears to be a factor associated with these rates. IMPLICATIONS: Low-density populations such as those in rural Appalachia deserve greater attention in cancer control research. The population-based cervical dysplasia rates reported here may be useful for comparisons in future investigations. PMID- 1608057 TI - Facial prosthetics ease cancer patient rehabilitation. PMID- 1608056 TI - Quality-of-life assessment in cancer clinical trials: a status report. PMID- 1608058 TI - Use of peak flow monitoring among urban black children with asthma. PMID- 1608059 TI - HIV disease as a cause of death for African Americans in 1987 and 1990. AB - Using death certificate data for 1987 and 1988 from the National Center for Health Statistics, combined with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS) surveillance data through December 1990 from the Centers for Disease Control, this article reports ranked mortality causes as a measure of the impact of the HIV epidemic within the African-American community. In 1987, while HIV/AIDS ranked 15th as a cause of death for all Americans, for African Americans the disease ranked 10th overall (third for African-American men, fifth for African-American women between 25 and 34 years of age, and ninth for African-American children ages 0 to 14). By 1990, it can be estimated that for all Americans HIV disease was the eight leading cause of death, but for African-Americans it ranked sixth overall. For African-American men between the ages of 35 and 44, HIV disease became the leading cause of death, accounting for 23.5% of all deaths. This disease was the second leading cause of death for African-American men and women between the ages of 25 and 35, and the eighth leading cause of death for African-American children ages 0 to 14. The implications of these findings are discussed. PMID- 1608060 TI - Violence: a challenge to the public health community. AB - In the past 2 years, cities have reported skyrocketing rates of violence, crime, and abusive behavior including intrafamilial homicides. Of the 1838 homicide deaths last year among teenagers between the ages of 15 and 19, 71% involved the use of a firearm. Among black males in the same age group, 82% of the deaths were associated with guns. Since 1968, homicide has been among the leading causes of death for black teenagers. These and large volumes of other data clearly indicate that violence and abusive behavior is a compelling public health problem. PMID- 1608061 TI - Black, middle-class women in San Antonio, Texas. AB - Fifty-six African-American women between the ages of 20 and 84 who had completed a minimum of 4 years of college and were employed in professional positions (eg, teacher, technician, lawyer, and physician) were identified in San Antonio, Texas. Specific information concerning marital status, income, home ownership, family of origin, presence of professional siblings, husbands' characteristics, medical and psychiatric health, and significant influences in their lives were obtained by a semistructured interview. This article summarizes the results of these interviews and presents the techniques used to identify this sample of African-American, middle-class women. PMID- 1608062 TI - Drew/Meharry/Morehouse Consortium Cancer Center: an approach to targeted research in minority institutions. AB - This article describes the process by which three private minority medical schools planned and developed a consortium cancer research center focusing on the prevention of cancer in the African-American population. Several lessons were learned that may have relevance as minority schools search for ways to improve the health status of blacks. PMID- 1608063 TI - The Cambridge Hospital Latino Health Clinic: a model for interagency integration of health services for Latinos at the provider level. AB - Latinos who present for health services often suffer from a complex interaction of medical and mental health needs, requiring a multifaceted intervention. An essential element of this multilevel approach is cultural and linguistic sensitivity on the part of health providers. New, innovative models of health service organization are needed to address the unique needs of the Latino population. Some of the key characteristics these models need to focus on include interagency collaboration rather than competition for resources, interdisciplinary teams of primary-care providers that also involve other nonmedical professional members, centralized case coordination and decentralized service delivery, flexibility and adaptability to changing priorities, continuity of care for all patients, and mutual support among providers to minimize the effects of stress and burnout. PMID- 1608064 TI - Experience of isolated sleep paralysis in clinical practice in Nigeria. AB - The supernatural fears associated with the experience of isolated sleep paralysis in the culture of developing countries is sometimes associated with the evolution of somatic symptoms of psychological origin in patients predisposed to neurotic illness. Patients rarely spontaneously volunteer these fears and doctors pay them scant attention. Illustrative case histories that demonstrate the dynamics of the clinical presentation, as well as the treatment approach, are highlighted. It is hoped that doctors in general medical practice and in psychological medicine in developing countries where belief in supernatural causation of illness is rife will consider these factors in order to provide more effective treatment. PMID- 1608065 TI - Sickle cell disease with complicated influenza B virus infection. AB - The Committee on Infectious Diseases of the American Academy of Pediatrics, and the Advisory Committee on Immunization Practices of the Center for Disease Control for many years have recommended the routine use of influenza vaccine in various hemoglobinopathies including sickle cell disease. This recommendation, however, has not been included in the patient care protocols of the Comprehensive Sickle Cell Centers program of NIHLB. Most clinicians have not used yearly influenza vaccine for their patients with sickle cell disease. This article reports a case of a 5-year-old boy with sickle cell disease who had not received influenza vaccine. He developed pneumonitis and acute myositis during a serologically confirmed influenza B virus infection. The incapacitating and protracted course of his illness presented diagnostic and management problems. His case strongly supports the recommendation of the two infectious disease committees. PMID- 1608066 TI - Concurrent phenomena of science and history in the 17th century and their essential interdependence. AB - The explanation for the explosion of science in the 17th century lies in history and medical historiography. Without this approach, it becomes fantasy, accidents, or success stories. Sigerist grasped the essential interdependence of science and history, and had no need for devised reasons or speculation. He realized that once the dark night of the Middle Ages was over, the sciences arose with undreamt of force and accelerated development. The advances in astronomy, mathematics, mechanics, and experimental science benefitted a society developing in seafaring, manufacture, and trade in the 17th century. Sigerist's views make the scientific explosion understandable in human and social terms. He did not overlook the capabilities of some extraordinary individuals, such as Paracelsus (1493-1541), to shape the course of medicine, nor the importance of the mechanistic philosophy in the 17th century. Man makes history and science; hence, we find concurrent phenomena of history and science essentially interdependent. The spirit of experimental science of 17th century England was inspired by the new needs of commercial enterprise for more means of transportation and communication. Likewise, the interest in the mechanics of the pump for waterworks and for the drainage of swamps led Harvey to think of the heart as a pump, and to explain the circulation of the blood in terms of its functioning. PMID- 1608067 TI - Recent developments on the hazards posed by 2,3,7,8-tetrachlorodibenzo-p-dioxin in soil: implications for setting risk-based cleanup levels at residential and industrial sites. AB - Since the publication of the Times Beach risk assessment in 1984, which suggested that residential soils were of concern when the level of 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) was in excess of 1 ppb, there has been continued interest in this topic. Studies conducted within the past 5 yr on the environmental and toxicological behavior of TCDD, as well as refinement of parameters regarding human exposure, indicate that previous assessments of the risk to humans posed by TCDD-contaminated soil were overestimated. In this paper, recent information drawn from nearly 100 recently published articles regarding the histopathology interpretation of the Kociba bioassay, environmental fate and half-life of TCDD in soil, and estimates of human exposure via soil ingestion, dermal contact, inhalation, surface runoff, and the consumption of fish were incorporated into a risk assessment. Cleanup levels for TCDD in residential and industrial soils were calculated based on most likely exposure scenarios. Probability distributions of key exposure parameters were incorporated into a Monte Carlo uncertainty analysis to predict the range and probability of TCDD uptake and corresponding cleanup levels in soil. This analysis demonstrated that the most significant route of human exposure to TCDD is through dermal contact with soil, followed by soil ingestion, fish consumption, and inhalation of airborne particulates. At residential sites, soils containing 20 parts per billion (ppb) of TCDD were found to pose a lifetime cancer risk no greater than 1 in 100,000 (10(-5) risk) under typical exposure conditions. Based on the Monte Carlo analysis, soil concentrations for the 75th and 95th percentile person were 12 and 7 ppb (10(-5) risk), respectively. In industrial soils, TCDD concentrations ranged between 131 and 582 ppb (10(-5) risk), depending on the amount of time spent outdoors under typical exposure conditions. Industrial soil concentrations of approximately 93 and 46 ppb (10(-5) risk) were calculated for the 75th and 95th percentile worker, respectively, engaged in outdoor activities. The range of TCDD concentrations in industrial soils was not reduced significantly when the consumption of fish from a neighboring waterway by off site receptors was considered. While cleanup levels for TCDD should be derived on a site-specific basis, this analysis indicated that soil cleanup standards can be generally higher than those implemented over the past 8 yr. PMID- 1608068 TI - Mutagenicity of organic emissions from unvented kerosene heaters in a chamber study. AB - A study was conducted to assess the mutagenicity of semivolatile organics and particle-bound organics emitted from unvented kerosene space heaters. The units tested included a well-tuned radiant heater and a maltuned convective heater. The tests were conducted in a 27-m3 chamber with a prescribed on/off heater usage pattern. The organic emissions were collected on Teflon-coated glass filters backed by XAD-2 resin. The dichloromethane-extractable organics from both the filters and the XAD were analyzed for nitropolycyclic hydrocarbons using gas chromatography/mass spectrometry, and were bioassayed for mutagenicity in microsuspension assays using Salmonella typhimurium strains TA98 with and without S9 and TA98NR (a nitroreductase-deficient strain) without S9. The results showed that both the semivolatile and particle-bound organics emitted from the kerosene heaters were mutagenic, and the presence of nitropolycyclic hydrocarbons in these organic emissions substantiated these findings. PMID- 1608069 TI - Effects of cocaine and norepinephrine on primary cultures of neonatal rat myocardial cells. AB - Sudden cardiac death associated with cocaine (Coc) abuse in healthy, physically active individuals became a grave concern in the late 1980s. It is well documented that physical activity increases circulating plasma catecholamine levels. Catecholamines as well as Coc are independently capable of inducing toxic cardiac effects. The purpose of this investigation was to evaluate the synergistic or additive toxic effects of norepinephrine (NE) and Coc in primary myocardial cell cultures obtained from 3- to 5-d-old Sprague-Dawley rats. Alterations in lactate dehydrogenase release (LDH), lysosomal neutral red retention (NR), beating activity, and morphology were evaluated after treatment of the cells for 1-24 h with 1 x 10(-3) M Coc alone, 1 x 10(-5) M Coc alone, 1 x 10(-5) M NE alone, 1 x 10(-3) M Coc with 1 x 10(-5) M NE, or 1 x 10(-5) M Coc with 1 x 10(-5) M NE. LDH release was elevated significantly after 24 h only with those cells exposed to 1 x 10(-3) M Coc alone and 1 x 10(-3) M Coc + 1 x 10(-5) M NE. Using NR retention as a score for lysosomal treatment of the cells with 1 x 10(-5) M Coc and 1 x 10(-3) M Coc alone did not decrease dye retention significantly. However, 1 x 10(-5) M NE combined with 1 x 10(-3) M Coc significantly reduced lysosomal dye retention as early as 1 h after treatment. After 24 h, 1 x 10(-5) M NE alone and 1 x 10(-5) M NE combined with 1 x 10(-5) M Coc significantly increased lysosomal fragility. Beating activity was altered in all treatment groups. Contractile activity was slow and irregular or completely absent with 1 x 10(-5) and 1 x 10(-3) M Coc, respectively. When NE (1 x 10(-5) M) was combined with both concentrations of Coc, there was distinct focalization of sharp, rapid contractions within the cells, which were asynchronous and/or arrhythmic in nature. Those cells exposed to 1 x 10(-5) M NE with 1 x 10(-5) M Coc for 24 h appeared hypercontracted with marked pseudopodia and cytoplasmic granule formation distinctly different from that exhibited by the cells exposed to 1 x 10(-5) M Coc alone. These data demonstrate that NE potentiates the adverse effects of Coc on contractile activity and morphology of spontaneously contracting neonatal myocardial cells maintained in culture. PMID- 1608070 TI - Frequencies of chromosomal aberrations in rodents collected in the coal-field and tobacco culture region of Criciuma, south Brazil. AB - The present work has been accomplished in the basin of the Sangao River (Criciuma, South Brazil), which receives the rejects from coal washing, mainly heavy metals. In the tobacco cultures at the river banks several agrotoxics are used. We tried to detect and estimate the possible action of this environmental pollution on rodents directly exposed to it through the study of chromosome aberration frequency in the bone marrow. The same methodology was applied to rodents collected from a nonpolluted area of the same state (Florianopolis, 190 km from Criciuma). The results obtained showed significant differences in total chromosome aberrations at the different sites. There is therefore a suggestion that this methodology could be applied to detect the action of environmental pollution on organisms. PMID- 1608072 TI - Umbilical vein entering the right atrium: significance of in utero diagnosis. PMID- 1608071 TI - Impalpable thoracic bony lesions diagnosed by sonographically guided needle aspiration biopsy. AB - Impalpable osteolytic lesions may be detected and diagnosed by ultrasonography and sonographically guided needle aspiration biopsy. Eleven cases with bone destruction found on chest radiographs were proved to be malignant by sonographically guided needle aspiration biopsy. The bony lesions were all hypoechoic and could be demonstrated easily. No complications or discomfort occurred after needle aspiration. Bony lesions can be detected by ultrasonography only when pathologic changes have occurred. Ultrasonography and sonographically guided needle aspiration biopsy provide a simple, convenient, and non-invasive method for detecting and diagnosing impalpable osteolytic lesions. PMID- 1608073 TI - Sonographic diagnosis of hydatids of Morgagni of the fallopian tube. PMID- 1608074 TI - The effect of intravenous furosemide on the Doppler waveform in normal kidneys. AB - Duplex Doppler sonography is currently being evaluated in the differentiation of obstructive and nonobstructive hydronephrosis. It was thought that this method may be of use in the diagnosis and follow-up of pelviureteric junction obstruction, and that its sensitivity may be increased by the use of intravenous furosemide to raise the intrarenal pressure in obstructive cases. Before embarking on a formal study, a pilot study was initiated to determine the effect of furosemide on the Doppler waveform of the normal kidney. Intravenous furosemide had variable effects on peak systolic and end-diastolic velocities and little significant effect on resistive index but caused a constant and dramatic subjective increase in vascularity. Possible modes of action are discussed. PMID- 1608075 TI - Fetal umbilical vein varix: sonographic appearance and postnatal outcome. AB - We describe five cases of dilation or varix of the umbilical portion of the left portal vein appearing as a fetal intra-abdominal cyst. Doppler or color flow examination, or both, indicated umbilical venous flow within the cystic area in each case. Only one fetus exhibited transient cardiomegaly, which resolved before birth. This fetus was the only one discovered to have the varix as early as the second trimester. All five infants were delivered at term without sequelae. PMID- 1608076 TI - Growth in twin gestations. PMID- 1608077 TI - The implications of sonographically identified cervical changes in patients not necessarily at risk for preterm birth. AB - Sonography of the cervix and lower uterine segment has been used in evaluating pregnancies at risk for incompetent cervix and premature labor. Shortened cervix (less than 3 cm) and open internal os with funneling of the membranes into the endocervical canal are sonographic features associated with premature delivery. We identified these sonographic signs in a group of 31 asymptomatic women who were undergoing prenatal sonography for multiple indications, not necessarily related to premature labor or cervical incompetence. Nineteen patients (61%) in this heterogeneous population had pregnancies complicated by preterm labor, clinical evidence of incompetent cervix, or preterm birth. We conclude that the presence of abnormal sonographic features of the cervix seen incidentally during prenatal sonography on asymptomatic patients warrants close clinical attention. PMID- 1608078 TI - Evaluation of adnexal masses with transvaginal color ultrasonography. PMID- 1608079 TI - Torsion of the testicular appendage. Sonographic diagnosis. AB - Torsion of the testicular appendages may simulate the clinical and physical examination findings of testicular torsion. Real-time imaging and duplex Doppler scanning aided the diagnosis of this entity in three children. The testes appear normal on sonograms and have normal vascular flow. A circular mass of increased echogenicity with a variably sized central hypoechoic region is seen adjacent to the testicle. We could not relate variations in echogenicity to time delay between clinical pain and sonographic examination. PMID- 1608080 TI - Coronal BPD revisited. PMID- 1608081 TI - Types, frequency, and significance of alternative diagnoses found during duplex Doppler venous examinations of the lower extremities. AB - This paper reports the alternative diagnoses identified during duplex Doppler venous examinations (DDVE) of the lower extremities and their significance in patient management to emphasize the importance of careful imaging of the site of maximum symptoms as well as of the venous system, particularly when a DDVE is negative for thrombus. Because numerous other papers have already verified the sensitivity, specificity, and criteria for the diagnosis of thrombophlebitis by ultrasonography, this study evaluates only the alternative diagnoses. In a 1-year period, 886 examinations were performed on 664 patients. Of these, 657 examinations (67%) in 457 patients were negative for deep vein thrombosis (DVT). Fifty-one of these examinations in 51 different patients resulted in an alternative positive diagnosis believed to account for the patient's symptoms. These 51 patients make up 11.25% of the patients negative for DVT (51/457), 5.7% of all examinations (51/886), and 7.7% of all patients studied (51/664). Alternative diagnoses, which occur frequently and are significant, should be considered when performing a DDVE, because ultrasonography is the only commonly used imaging modality by which these alternative diagnoses can be made. PMID- 1608082 TI - Sonographic detection of duodenal ulcer. AB - Using a wall thickness of greater than 5 mm for the first portion of the duodenum as the criterion for the sonographic diagnosis of duodenal ulcer, we studied the value of sonography in detecting this lesion. Endoscopy (88 patients) and upper gastrointestinal barium studies (12 patients) were used as the gold standards for the diagnosis. The study included 100 patients in whom gastrointestinal disease was suspected (20 with duodenal ulcer and 80 with normal findings). Of the 20 duodenal ulcers verified by endoscopy or upper gastrointestinal series, 13 patients had duodenal wall thickening, six had normal wall thickness, and one was nondiagnostic. Of the 80 subjects with normal findings on endoscopy or upper gastrointestinal series, 73 patients had a normal duodenum, four had wall thickening, and three were nondiagnostic. Considering the four nondiagnostic cases as sonographic errors, there were six false-negative cases and four false positive cases (a sensitivity of 65%, specificity of 91%, positive predictive value of 76%, and negative predictive value of 92%). Our results show that sonography is not sufficiently sensitive to be used as a screening test, nor is it specific for duodenal ulcer, but a thickened duodenal wall of over 5 mm on sonography warrants additional work-up. PMID- 1608084 TI - The needle tip echo. AB - The echo of the needle tip used in sonographically guided needle aspiration biopsies was studied in A mode. The biopsy transducer was placed in a water tank and needles parallel to the beam axis were used. The beveled needle tip produced two echoes, which were probably generated by diffraction at the edge of the far end of the tip and by the sharp edge of the needle tip opening. The distal echo was more intense than the proximal one. When a stylet was inserted the proximal echo disappeared as the diffracting edges decreased to a single echo. Inserting a stylet did not enhance the echoes. Roughening of the needle shaft did not enhance echogenicity, whereas side ports in the shaft produced a greater number of echo peaks. PMID- 1608083 TI - Peripheral arterial Doppler ultrasonography: diagnostic criteria. AB - Fifty-one patients (86 legs) were studied from the aorta to the popliteal artery with both duplex ultrasonography and arteriography with the intention of establishing diagnostic ultrasonographic criteria for degrees of stenosis greater than 50% and determining the effect of multi-segment disease on the accuracy of these criteria. Receiver operator characteristic curves were used to determine diagnostic criteria for greater than 50%, greater than 70%, greater than 90% diameter stenoses or occlusions. A stenosis of greater than 70% was diagnosed either if the peak systolic velocity was more than 160 cm/sec (sensitivity 77%, specificity 90%) of if there was an increase in peak systolic velocity of 100% with respect to the arterial segment above the stenosis (sensitivity 80%, specificity 93%). Sequential stenoses were detected with lesser sensitivities. Ratio criteria were more accurate than peak systolic velocity for all degrees of stenosis. For detection of occlusion, duplex ultrasonography was 92% sensitive and 99% specific. PMID- 1608085 TI - Comparison of fetal cerebellar measurements by two different techniques. AB - We examined 53 fetuses between 15 and 40 weeks of gestation with transverse and coronal sections of the head in order to evaluate the accuracy and reproducibility of the coronal cerebellar diameter. Intraobserver coefficient of variation was less than or equal to 2.2% and the mean interobserver difference was 2.2% (range, 0 to 6%). A positive linear correlation exists between transverse and coronal measurements (coronal diameter = 1.02 x transverse diameter - 0.48; R2 = 0.99; P less than 0.0001). We conclude that the coronal cerebellar diameter is reproducible and accurate and when indicated clinically can be used instead of the transverse cerebellar diameter when the latter is not obtainable because of fetal position. PMID- 1608086 TI - Adult transcranial Doppler. PMID- 1608087 TI - Normal and respiratory variations of the hepatic and portal venous duplex Doppler waveforms with simultaneous electrocardiographic correlation. AB - To understand hepatic vein (HV) and portal vein (PV) duplex waveforms and their normal and respiratory variations, HV and PV duplex sonography with simultaneous electrocardiography was performed on 11 volunteers. Absolute velocities of the waveforms' components and their ratios were determined at mid-inspiration, full inspiration, full expiration, and Valsalva maneuver. The normal HV waveform was variable in shape and component velocities and ratios but essentially consisted sequentially of (1) an antegrade systolic wave resulting from movement of the tricuspid annulus toward the cardiac apex and occurring shortly after QRS; (2) a retrograde v-wave resulting from atrial overfilling and occurring immediately after the T-wave; (3) an antegrade diastolic wave resulting from opening of the tricuspid valve and occurring shortly after the T-wave; and (4) a retrograde a wave resulting from atrial contraction and occurring immediately after the P wave. The ratio of the maximum systolic velocity to maximum diastolic velocity varied from 1.0 to 2.8 (mean 1.4). Systolic-to-diastolic ratio decreased during inspiration but was always greater than 0.6 and increased during expiration. The Valsalva maneuver diminished waveform pulsatility. PV waveforms were more triphasic than biphasic but less pulsatile, flow was totally antegrade, and respiratory changes were less remarkable than HV waveforms. All normal HV and most normal PV waveforms showed multiphasicity that corresponded to cyclic cardiac changes. The shapes of these waveforms were variable and were modified by respiratory movements. PMID- 1608088 TI - Antenatal diagnosis of horseshoe kidney. PMID- 1608089 TI - Uterine-umbilical artery Doppler velocimetry in pregnant women with systemic lupus erythematosus. AB - We evaluated continuous wave uterine-umbilical artery Doppler velocimetry for predicting pregnancy outcome in women with systemic lupus erythematosus (SLE). Lupus anticoagulant (LAC) and anticardiolipin (ACL) antibody status also were correlated with Doppler results and outcome. Three Doppler vascular patterns were identified in 27 pregnancies of 26 women with SLE. Patients with normal flow velocity in both vessels had normal outcomes (n = 18). Reduced flow velocity of the umbilical artery only was present in five women, whose newborn infants were of lesser gestational age and birthweight, two being small for gestational age. In four pregnancies reduced flow velocity was noted in both vessels. These cases had the poorest outcome, with three perinatal losses and all fetuses being small for gestational age. Doppler velocimetry showed 100% sensitivity and negative predictive value in the detection of the small for gestational age fetus and abnormal antepartum fetal heart rate tracing. Fourteen of 18 women with normal Doppler studies did not have preeclampsia or SLE flare-ups, whereas all nine women with abnormal Doppler studies had such complications. In all 27 pregnancies the women were screened for LAC, and 21 women also were tested for the ACL antibody. Poor correlation was found between antiphospholipid antibody status and Doppler results in three of the six pregnancies with positive antibody testing the patients had normal Doppler studies and outcomes. Thus, Doppler velocimetry may help determine when these substances will affect the outcome adversely. In this study the umbilical-placental vascular system was affected more often. Uterine-umbilical arterial Doppler velocimetry uniquely identified the fetus at risk for adverse perinatal outcome in pregnancies complicated by SLE. Thus, it is a potentially valuable tool in clarifying the pathophysiology and in the management of SLE in pregnancy. PMID- 1608090 TI - Extension of saphenous thrombophlebitis into the femoral vein: demonstration by color flow compression sonography. AB - Five cases are presented in which compression and color flow sonography were used to diagnose extension of superficial saphenous thrombophlebitis into the deep system at the saphenofemoral junction. In one case thrombus originated in the calf, demonstrating an unusual mode of propagation into the deep venous system above the knee. Color Doppler imaging is especially helpful in diagnosing this complication of superficial thrombophlebitis. PMID- 1608091 TI - Dural sinus ectasia after prolonged nuchal cord encirclement. PMID- 1608092 TI - Contained rupture of the inferior vena cava: diagnosis by ultrasonography and magnetic resonance imaging. PMID- 1608093 TI - Prenatal diagnosis of congenital hiatal hernia. PMID- 1608094 TI - Antenatal sonographic features of Walker-Warburg syndrome. Value of endovaginal sonography. PMID- 1608095 TI - Prenatal diagnosis of cystic adenomatoid malformation of one fetus in a twin pregnancy: an unusual presentation. PMID- 1608096 TI - Diagnosis of phocomelia by transvaginal sonography. PMID- 1608097 TI - Trend to specialization reversing? PMID- 1608098 TI - Less maligned, but cut from the same cloth, other silicone implants also have adverse effects. PMID- 1608099 TI - Surgeons grapple with synovitis, fractures around silicone implants for hand and wrist. PMID- 1608100 TI - Clinical decision making: from theory to practice. Cost-effectiveness analysis. Will it be accepted? PMID- 1608101 TI - From the National Institutes of Health. PMID- 1608102 TI - From the Centers for Disease Control. HIV prevention in US correctional system, 1991. PMID- 1608103 TI - From the Centers for Disease Control. HIV seroprevalence among adults treated for cardiac arrest before reaching a medical facility. PMID- 1608104 TI - A piece of my mind. The person with the disease. PMID- 1608105 TI - How the doctor got gagged. PMID- 1608106 TI - How the doctor got gagged. PMID- 1608107 TI - Diuretics, potassium, and ventricular arrhythmias. PMID- 1608108 TI - Diuretics, potassium, and ventricular arrhythmias. PMID- 1608109 TI - Drug company sponsorship of education: the response to the FDA draft concept paper. PMID- 1608110 TI - Circumcision and urinary tract infection. PMID- 1608111 TI - Circumcision and urinary tract infection. PMID- 1608112 TI - Circumcision and urinary tract infection. PMID- 1608113 TI - Circumcision and urinary tract infection. PMID- 1608114 TI - Chemotherapy of metastatic breast cancer in the elderly. The Piedmont Oncology Association experience [see comment]. AB - OBJECTIVE: To determine the effect of age on treatment outcome in women with metastatic breast cancer treated with chemotherapy. DESIGN: Case-comparison study of patients with metastic breast cancer treated in five clinical trials of the Piedmont Oncology Association. SETTING: University and private practice physicians participating in the Piedmont Oncology Association clinical trials in the southeastern United States. PATIENTS: Seventy patients 70 years of age or older were compared with 60 patients aged 50 through 69 years and 40 patients less than 50 years of age. All patients were ambulatory or capable of self-care, with adequate hematologic, renal, and hepatic function. INTERVENTIONS: Treatment with multidrug chemotherapy regimens. MAIN OUTCOME MEASURES: Response to treatment, time to disease progression, survival, and toxic effects. RESULTS: Pretreatment characteristics including race, performance status, disease-free interval, prior therapy, sites of metastatic disease, and number and dominant sites of metastases were similar for the three age groups. The response rates for the younger-than-50, 50-through-69, and 70-or-older age groups were 40%, 31%, and 29%, respectively (P = .53). There were no significant differences in time to disease progression or survival for patients in the three age groups. Estimates for time to progression and survival were 9.1 and 17.9 months, 6.2 and 12.8 months, and 7.2 and 14.2 months, respectively. Toxic effects, dose delivery, and dose delays were also similar for all three age groups. CONCLUSIONS: Women 70 years of age or older who were enrolled in these trials were similar to their younger counterparts in response rates, time to disease progression, survival, and toxic effects. Women in this age group should not be excluded, based on age alone, from clinical trials involving chemotherapy for advanced breast cancer. PMID- 1608115 TI - A prospective study of exercise and incidence of diabetes among US male physicians. AB - OBJECTIVE: To examine prospectively the association between regular exercise and the subsequent development of non-insulin-dependent diabetes mellitus (NIDDM). DESIGN: Prospective cohort study including 5 years of follow-up. PARTICIPANTS: 21,271 US male physicians participating in the Physicians' Health Study, aged 40 to 84 years and free of diagnosed diabetes mellitus, myocardial infarction, cerebrovascular disease, and cancer at baseline. Morbidity follow-up was 99.7% complete. MAIN OUTCOME MEASURE: Incidence of NIDDM. RESULTS: At baseline, information was obtained about frequency of vigorous exercise and other risk indicators. During 105,141 person-years of follow-up, 285 new cases of NIDDM were reported. The age-adjusted incidence of NIDDM ranged from 369 cases per 100,000 person-years in men who engaged in vigorous exercise less than once weekly to 214 cases per 100,000 person-years in those exercising at least five times per week (P, trend, less than .001). Men who exercised at least once per week had an age adjusted relative risk (RR) of NIDDM of 0.64 (95% Cl, 0.51 to 0.82; P = .0003) compared with those who exercised less frequently. The age-adjusted RR of NIDDM decreased with increasing frequency of exercise: 0.77 for once weekly, 0.62 for two to four times per week, and 0.58 for five or more times per week (P, trend, .0002). A significant reduction in risk of NIDDM persisted after adjustment for both age and body-mass index: RR, 0.71 (95% Cl, 0.56 to 0.91; P = .006) for at least once per week compared with less than once weekly, and P, trend, .009, for increasing frequency of exercise. Further control for smoking, hypertension, and other coronary risk factors did not materially alter these associations. The inverse relation of exercise to risk of NIDDM was particularly pronounced among overweight men. CONCLUSIONS: Exercise appears to reduce the development of NIDDM even after adjusting for body-mass index. Increased physical activity may be a promising approach to the primary prevention of NIDDM. PMID- 1608116 TI - Association of prior infection with Chlamydia pneumoniae and angiographically demonstrated coronary artery disease. AB - OBJECTIVE: To evaluate the association between prior infection with Chlamydia pneumoniae, as measured by IgG antibody, and coronary artery disease. DESIGN: A population-based, case-control study. SETTING: Group Health Cooperative of Puget Sound, a Seattle-based health maintenance organization. PARTICIPANTS: Men 55 years of age and younger and women 65 years of age and younger. Cases (n = 171) were members of Group Health Cooperative undergoing diagnostic coronary angiography who had at least one coronary artery lesion occupying 50% or more of the luminal diameter. The population controls (n = 120) were Group Health Cooperative members without known coronary heart disease. MAIN OUTCOME MEASURE: The adjusted odds ratio (OR) for coronary artery disease associated with prior C pneumoniae infection as measured by the presence of IgG antibody. RESULTS: After adjusting for age, gender, and calendar quarter of blood drawing, the OR for coronary artery disease associated with the presence of antibody was 2.6 (95% confidence interval, 1.4 to 4.8). The association was limited to cigarette smokers, in whom the OR was 3.5 (95% confidence interval, 1.7 to 7.0). Among never-smokers, the OR was 0.8 (95% confidence interval, 0.3 to 1.9). When cases and controls were restricted to those assayed concurrently, the adjusted OR (smokers and nonsmokers combined) was 4.2 (95% confidence interval, 1.8 to 10.0). Adjustment for serum cholesterol, hypertension, alcohol use, diabetes, and socioeconomic status did not change these results. Only a week association was found when cases were compared with 63 subjects whose angiographic results were normal (OR, 1.2; 95% confidence interval, 0.6 to 2.2). CONCLUSIONS: These results generally support the previously reported association between C pneumoniae infection and coronary heart disease. However, caution should be used in interpreting the basis for this association. PMID- 1608117 TI - New evidence of the prevalence and scope of physician joint ventures. AB - Physician ownership of health care businesses (outside their own practice) to which they refer patients has attracted considerable attention in the medical literature, in the media, and from federal and state policymakers. Despite the concerns raised about these ownership arrangements, known as joint ventures, the prevalence and scope of joint ventures involving physicians is not well documented. This report examines the prevalence and scope of physician joint ventures in Florida based on data collected under a legislative mandate. Our results indicate that physician ownership of health care businesses providing diagnostic testing or other ancillary services is common in Florida. While this conclusion is based on our comprehensive survey of health care businesses in Florida, it is at least indicative that such arrangements are likely to occur elsewhere. We find that at least 40% of Florida physicians involved in direct patient care have an investment interest in a health care business to which they may refer their patients for services; over 91% of the physician owners are concentrated in specialties that may refer patients for services. About 40% of the physician investors have a financial interest in diagnostic imaging centers. The estimates reported here indicate that the proportion of referring physicians involved in direct patient care who participate in joint ventures is much higher than previous estimates suggest. PMID- 1608118 TI - The problem of physician self-referral under the Medicare and Medicaid antikickback statute. The Hanlester Network case and the safe harbor regulation. AB - Dramatic changes have taken place in the legal and ethical status of physician self-referral. In July 1991, the US Department of Health and Human Services issued the "safe harbor" regulation, which permits self-referral only under very narrow constraints. In September 1991, the Department of Health and Human Services Departmental Appeals Board ruled in the landmark Hanlester Network case that joint venture profit distributions are illegal under the antikickback statute when intended to influence investors' reason or judgment in referring Medicare or Medicaid patients. Following this principle on remand in March 1992, the Administrative Law Judge precedentially held that profit distributions violated the statute. Before this remand decision, the Departmental Appeals Board ruling and the safe harbor regulation started the pendulum swinging against self referral as seen, for example, in the December 1991 revised American Medical Association ethical guidelines. To help providers operate in this new legal and ethical climate, legislation is needed to authorize case-by-case safe harbors. PMID- 1608119 TI - The treatment of cancer in an aging population. PMID- 1608120 TI - Must the law assure ethical behavior? PMID- 1608121 TI - Women scientists explore more ways to smash through the 'glass ceiling'. PMID- 1608122 TI - Medical exorcism required as revitalized revenant of tuberculosis haunts and harries the land. PMID- 1608123 TI - United States loses lead in contraceptive choices, R&D; changes in tort liability, FDA review urged. PMID- 1608124 TI - From the Food and Drug Administration. PMID- 1608125 TI - From the Centers for Disease Control. Prostate cancer trends--United States, 1980 1988. PMID- 1608127 TI - Social and economic factors in patients with coronary disease. PMID- 1608126 TI - From the Centers for Disease Control. Changes in sexual behavior and condom use associated with a risk-reduction program--Denver. PMID- 1608128 TI - Social and economic factors in patients with coronary disease. PMID- 1608129 TI - Social and economic factors in patients with coronary disease. PMID- 1608130 TI - Social and economic factors in patients with coronary disease. PMID- 1608131 TI - Social and economic factors in patients with coronary disease. PMID- 1608132 TI - Social and economic factors in patients with coronary disease. PMID- 1608133 TI - Distress over the noneffect of stress. PMID- 1608134 TI - Distress over the noneffect of stress. PMID- 1608135 TI - Distress over the noneffect of stress. PMID- 1608136 TI - Depressive symptoms in the community. PMID- 1608137 TI - 'Beverly Hills, 90210': The lap belts don't show on TV. PMID- 1608138 TI - Factors influencing the testing for driving under the influence. PMID- 1608139 TI - Monitoring for myocardial ischemia during noncardiac surgery. A technology assessment of transesophageal echocardiography and 12-lead electrocardiography. The Study of Perioperative Ischemia Research Group. AB - OBJECTIVE: Transesophageal echocardiography (TEE) and 12-lead electrocardiography (ECG) are sophisticated techniques that are increasingly being used to monitor for myocardial ischemia during noncardiac surgery. We examined whether the routine use of these techniques has incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes when compared with preoperative clinical data and intraoperative monitoring using continuous two lead bipolar ECG. DESIGN: Cohort study. SETTING: Veterans Affairs medical center. PATIENTS: A total of 332 men undergoing noncardiac surgery who had or were at high risk for coronary artery disease. INTERVENTIONS: TEE, 12-lead ECG, and two lead ECG were performed continuously during noncardiac surgery (47% vascular, 53% nonvascular). Monitoring results were not available to anesthesiologists or surgeons, and data were blindly analyzed after surgery. MAIN OUTCOME MEASURE: Perioperative ischemic outcomes (cardiac death, nonfatal myocardial infarction, unstable angina). RESULTS: In a subset of 285 patients who were adequately studied by all three techniques, 111 patients (39%) were identified as having intraoperative myocardial ischemia (by one or more monitoring techniques). By univariate analysis, intraoperative ischemia was associated with all perioperative cardiac outcomes, including ischemic outcomes, congestive heart failure, and ventricular tachycardia (P less than or equal to .02 for each of the three monitoring techniques). However, when monitoring results for TEE and 12 lead ECG were added to a multivariate model that included preoperative clinical data and continuous two-lead ECG results, the incremental value of TEE was small (odds ratio, 2.6; 95% confidence interval [CI], 1.2 to 5.7; P = .02) and that of 12-lead ECG was not significant (odds ratio, 1.5; 95% CI, 0.6 to 3.8). Furthermore, when the multivariate analysis was repeated with only ischemic outcomes, neither TEE nor 12-lead ECG retained significant associations (odds ratio, 2.2; 95% CI, 0.5 to 9.4, and odds ratio, 1.1; 95% CI, 0.2 to 6.1, respectively). CONCLUSION: When compared with preoperative clinical data and intraoperative monitoring using two-lead ECG, routine monitoring for myocardial ischemia with TEE or 12-lead ECG during noncardiac surgery has little incremental clinical value in identifying patients at high risk for perioperative ischemic outcomes. PMID- 1608140 TI - Ventricular arrhythmias in patients undergoing noncardiac surgery. The Study of Perioperative Ischemia Research Group. AB - OBJECTIVE: To determine the incidence, clinical predictors and prognostic importance of perioperative ventricular arrhythmias. DESIGN: Prospective cohort study (Study of Perioperative Ischemia). SETTING: University-affiliated Department of Veterans Affairs Medical Center, San Francisco, Calif. SUBJECTS: A consecutive sample of 230 male patients, with known coronary artery disease (46%) or at high risk of coronary artery disease (54%), undergoing major noncardiac surgical procedures. MEASUREMENTS: We recorded cardiac rhythm throughout the preoperative (mean = 21 hours), intraoperative (mean = 6 hours), and postoperative (mean = 38 hours) periods using continuous ambulatory electrocardiographic monitoring. Adverse cardiac outcomes were noted by physicians blinded to information about arrhythmias. MAIN RESULTS: Frequent or major ventricular arrhythmias (greater than 30 ventricular ectopic beats per hour, ventricular tachycardia) occurred in 44% of our patients: 21% preoperatively, 16% intraoperatively, and 36% postoperatively. Compared with the preoperative baseline, the severity of arrhythmia increased in only 2% of patients intraoperatively but in 10% postoperatively. Preoperative ventricular arrhythmias were more common in smokers (odds ratio [OR], 4.1; 95% confidence interval [CI], 1.2 to 15.0), those with a history of congestive heart failure (OR, 4.1; 95% CI, 1.9 to 9.0), and those with electrocardiographic evidence of myocardial ischemia (OR, 2.2; 95% CI, 1.1 to 4.7). Preoperative arrhythmias were associated with the occurrence of intraoperative and postoperative arrhythmias (OR, 7.3; 95% CI, 3.3 to 16.0, and OR, 6.4; 95% CI, 2.7 to 15.0, respectively). Nonfatal myocardial infarction or cardiac death occurred in nine men; these outcomes were not significantly more frequent in those with prior perioperative arrhythmias, albeit with wide CIs (OR, 1.6; 95% CI, 0.4 to 6.2). CONCLUSION: Almost half of all high-risk patients undergoing noncardiac surgery have frequent ventricular ectopic beats or nonsustained ventricular tachycardia. Our results suggest that these arrhythmias, when they occur without other signs or symptoms of myocardial infarction, may not require aggressive monitoring or treatment during the perioperative period. PMID- 1608141 TI - Detection and significance of intraoperative and postoperative myocardial ischemia in peripheral vascular surgery. AB - OBJECTIVE: To determine the incidence and significance of intraoperative and postoperative myocardial ischemia and their relationship to preoperative ischemia and postoperative cardiac events in patients undergoing peripheral arterial surgery. DESIGN: Prospective cohort trial. PATIENTS: One hundred fifteen patients undergoing elective vascular surgery who met predefined eligibility criteria and were thought to have acceptable cardiac risk as assessed by independent cardiologists. INTERVENTIONS: Ambulatory electrocardiographic monitoring preoperatively, intraoperatively, and up to 72 hours postoperatively. MEASUREMENTS: Preoperative clinical characteristics and laboratory data were collected. Predefined adverse cardiac events were identified by an investigator who was "blinded" to monitoring results. Monitor recordings were interpreted for ST-segment depression by investigators blinded to patient information. MAIN RESULTS: Intraoperative ischemia was present in 21 patients (18%), and postoperative ischemia was present in 35 (30%). There were 16 postoperative cardiac events. The relative risk of suffering a cardiac event was 2.7 in patients with intraoperative ischemia and was 16 in patients with postoperative ischemia. Preoperative ischemia closely correlated with intraoperative and postoperative ischemia. Preoperative and postoperative ischemia preceded cardiac events in 14 of 16 patients. CONCLUSIONS: Preoperative ischemia appears to identify high-risk patients, and subsequent perioperative monitoring detects silent ischemia that commonly precedes clinical events and that may be treatable with anti-ischemia therapy. PMID- 1608142 TI - In-hospital and long-term mortality in male veterans following noncardiac surgery. The Study of Perioperative Ischemia Research Group. AB - OBJECTIVES: To determine the causes of and risk factors for mortality following noncardiac surgery. DESIGN: Prospective cohort study. SETTING: A university affiliated Veterans Affairs medical center. PATIENTS: Consecutive series of 474 men between the ages of 38 and 89 years (mean age, 68 years) who were undergoing major noncardiac surgery involving general anesthesia. All subjects had known coronary artery disease or were at high risk for coronary artery disease. MEASUREMENTS AND RESULTS: During the initial hospitalization, 26 patients (5%) died, most commonly from sepsis (n = 6) or cardiac diseases (n = 6). Deaths occurred from postoperative days 2 to 69; half occurred more than 3 weeks after surgery. Multivariable analysis disclosed that a history of hypertension (odds ratio [OR] = 3.8; 95% confidence interval [CI], 1.1 to 13), a severely limited activity level (OR = 9.7; 95% CI, 2.5 to 37), and a creatinine clearance of less than 0.83 mL/s (OR = 6.8; 95% CI, 2.8 to 16) were all independently associated with an increased risk of postoperative mortality. The mortality rate in patients with two or more of these risk factors was 20%, nearly eight times higher (95% CI, 3.6 to 16) than those with one or no risk factors. An additional 82 patients died within the next 2 years; cancer, renal dysfunction, congestive heart failure, and obstructive pulmonary disease were independently associated with long-term mortality. CONCLUSIONS: Even in patients at high risk of cardiac complications following surgery, noncardiac causes of death are more common. Patients with a history of hypertension, severely limited activity, and reduced renal function appear to be at especially high risk of in-hospital mortality after noncardiac surgery. PMID- 1608143 TI - Long-term cardiac prognosis following noncardiac surgery. The Study of Perioperative Ischemia Research Group. AB - OBJECTIVE: To determine the long-term (2-year) cardiac prognosis of high-risk patients undergoing noncardiac surgery and to determine the predictors of long term adverse cardiac outcome. DESIGN: Prospective cohort study. Historical, clinical, and laboratory data were collected during the in-hospital period, and at 6 months, 1 year, and 2 years following surgery. Data were analyzed using proportional hazards models. SETTING: University-affiliated Veterans Affairs medical center. POPULATION: A consecutive sample of 444 patients with or at high risk for coronary artery disease who had undergone elective noncardiac surgery and were discharged from the hospital in stable condition. MAIN OUTCOME MEASURES: Cardiac death, myocardial infarction, unstable angina, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty, and new unstable angina requiring hospitalization. RESULTS: Forty-seven patients (11%) had major cardiovascular complications during a 728-day (median) follow-up period: 24 had cardiac death; 11, nonfatal myocardial infarction; six, progressive angina requiring coronary artery bypass graft surgery or coronary angioplasty; and six, new unstable angina requiring hospitalization. Thirty percent of outcomes occurred within 6 months of surgery and 64% within 1 year. Five independent predictors of long-term outcome were identified. Three predictors reflected the preexisting chronic disease state: (1) the presence of known vascular disease (hazard ratio, 6.1; 95% confidence interval [CI], 2.5 to 15.0; P less than .0001); (2) a history of congestive heart failure (hazard ratio, 5.0; 95% CI, 2.0 to 12.0; P less than .0005); and (3) known coronary artery disease (hazard ratio, 3.7; 95% CI, 1.7 to 8.0; P less than .0007). Two predictors reflected acute postoperative ischemic events: (1) myocardial infarction/unstable angina (hazard ratio, 20; 95% CI, 7.5 to 53.0; P less than .0001) and (2) myocardial ischemia (hazard ratio, 2.2; 95% CI, 1.1 to 4.3; P less than .03). Patients surviving a postoperative in-hospital myocardial infarction had a 28-fold increase in the rate of subsequent cardiac complications within 6 months following surgery, a 15-fold increase within 1 year, and a 14-fold increase within 2 years (95% CI, 5.8 to 32; P less than .00001). Seventy percent of all long-term adverse outcomes were preceded by in-hospital postoperative ischemia that occurred at least 30 days (median, 282 days) before the long-term event. The development of congestive heart failure or ventricular tachycardia (without ischemia) during hospitalization was not associated with adverse long term outcome. CONCLUSIONS: The incidence of long-term adverse cardiac outcomes following noncardiac surgery is substantial. At increased risk are patients with chronic cardiovascular disease; at highest risk are patients with acute perioperative ischemic events. We conclude that survivors of in-hospital perioperative ischemic events, specifically myocardial infarction, unstable angina, and postoperative ischemia, warrant more aggressive long-term follow-up and treatment than is currently practiced. PMID- 1608144 TI - Rheumatoid arthritis-like deformities in an early 16th-century painting of the Flemish-Dutch school. AB - Hand deformities resembling those of rheumatoid arthritis have been depicted in a painting by an anonymous artist of the Flemish-Dutch School, mid-15th to early 16th century. The painting is presently in the Escorial Museum near Madrid, Spain. This observation, like other earlier observations of rheumatoid deformities in paintings of the Middle Ages, suggests that rheumatoid arthritis is not a modern disease; it had, indeed, appeared several centuries before Landre Beauvais' description in 1800. PMID- 1608145 TI - Anesthesia and major noncardiac surgery. PMID- 1608146 TI - Prenatal hemoglobinopathy screening. PMID- 1608147 TI - [Effects of anesthesia on the metabolic response during pelvic surgery]. AB - Dividing anesthesia for gynecological laparotomy into nitrous oxide-oxygen halothane (GOF) anesthesia (group A), nitrous oxide-oxygen (GO) plus ketamine anesthesia (group B) and GOF plus epidural anesthesia (group C), we studied effects of each anesthesia on circulatory and metabolic systems. During the operation, influence on the heart rate was slight in three groups, while systolic pressure decreased significantly in group C. The lactic acid in the blood was elevated in three groups, but the elevation was least in group C. The elevation of lactic acid pyruvic acid ratio (L/P) was less in group C. The blood glucose level was elevated significantly in three groups, and it was highest in group A. On the other hand NEFA was elevated significantly in group A, while no change was noted in group B, and decreasing was noted in group C. The results indicate that no large influence of each anesthesia on the metabolic system was noted in group A and B, and its influence was the least in group C. PMID- 1608148 TI - [Effects of halothane, caffeine and ryanodine on the intracellular calcium store in blood mononuclear cells]. AB - To evaluate the possibility of using blood cells in the screening test for susceptibility to malignant hyperthermia (MH), we examined the effect of halothane and caffeine on cytoplasmic free calcium concentration ([Ca]i) in mononuclear cells. Blood mononuclear cells were isolated from guinea pigs or normal human volunteers, loaded with fura-2 AM and changes in the calcium signal (340nm/380nm ratio) after the application of halothane and/or caffeine were measured. Halothane above 5 mM caused a large increase in [Ca]i, but this increase was mostly abolished by the removal of extra-cellular calcium using EGTA. On the other hand, caffeine caused no observable change in the calcium signal. Pre-treatment with ryanodine did not change the calcium signal brought about by halothane or ionomycin. We conclude from this study that there is no calcium-induced calcium release (CICR) mechanism detectable by this method in blood mononuclear cells. As we consider that the main cause of the typical MH is the abnormality in the CICR mechanism, it seems difficult to screen MH susceptibility by using blood mononuclear cells. Further studies will be necessary using MH susceptible swines or patients. PMID- 1608149 TI - [Surgical stress stimulates release of polymorphonuclear leukocyte elastase from a segmented neutrophil]. AB - The studies were performed to find out whether increased serum levels of polymorphonuclear leukocyte elastase (PMNE) depend on increase of segmented neutrophils or increase of PMNE release from a segmented neutrophil on 17 patients for various elective surgeries. Serum levels of PMNE, leukocyte count and leukogram were determined before incision (preoperation), as well as on the 1st, 3rd and 5th day after operation. Serum levels of PMNE, segmented cell count, stab cell count, stab cell-segmented cell ratio increased most on the 1st postoperative day and decreased thereafter. Leukocyte count showed no significant changes. Serum levels of PMNE correlated well with PMNE released from a segmented neutrophil, but not with leukocyte count or segmented cell count. It was concluded that increased serum levels of PMNE by surgical stress depend on the increased PMNE release from a segmented neutrophil but not on the increased segmented cell count. PMID- 1608150 TI - [Endocrine effects of induced hypotension by ketanserin in anesthetized dogs]. AB - Plasma levels of catecholamines, aldosterone and cortisol as well as plasma renin activity during hypotension by ketanserin were studied in 9 mongrel dogs under 0.87% halothane in oxygen (1MAC). Mean arterial pressure was reduced and maintained at 60 mmHg for 60 minutes by the infusion of 0.1% ketanserin solution. Plasma norepinephrine decreased progressively during hypotension to 35% of the control value after induced hypotension. In contrast, plasma epinephrine increased three-four folds compared with the control value during and after induced hypotension, but this change was not statistically significant. Plasma renin activity and plasma aldosterone showed a slight increase during hypotension but returned toward the control value after discontinuing the infusion of ketanserin. Plasma cortisol remained unchanged throughout the experiment. In conclusion, our data show that hypotension by ketanserin is not accompanied by the activation of the renin-angiotensin-sympathetic system or adrenocortical system. PMID- 1608151 TI - [Effects of tizanidine, a central muscle relaxant, upon spinal reflexes]. AB - Effects of intravenous administration of tizanidine upon spinal reflexes were studied in cats anesthetized with urethane-chloralose. Both extensor and flexor monosynaptic reflexes and polysynaptic flexor reflex were inhibited by intravenous administration of tizanidine in a dose of 10-50 micrograms.kg-1. The inhibition was dose-dependent. After strychnine administration, polysynaptic flexor reflex was augmented, but the inhibition by tizanidine administration was unaffected. In spinal cats, inhibitory effect of tizanidine upon monosynaptic reflex was weaker than in intact cats. Viscero-intercostal reflex elicited by electrical stimulation of A delta afferent fibers in the greater splanchnic nerve was also inhibited by intravenous tizanidine (25 micrograms.kg-1). The degree of inhibition decreased in parallel with increase in the intensity of stimulus applied to the greater splanchnic nerve. PMID- 1608152 TI - [The change in cerebral blood flow during hypotensive anesthesia induced by prostaglandin E1]. AB - We investigated the effect of prostaglandin E1 (PGE1)--induced hypotension during sevoflurane anesthesia on the cerebral blood flow (CBF), autoregulation and internal jugular venous O2 tension (PjO2) in 8 patients undergoing neurosurgery. Although the mean arterial pressure decreased from 95.3 +/- 3.8 mmHg (mean +/- SD) to 63.6 +/- 8.0 mmHg by continuous intravenous infusion of PGE1, CBF did not change significantly (97.2 +/- 10.6% of control value). During hypotensive anesthesia, autoregulation was well maintained in all patients, and the values of PjO2 did not suggest brain hypoxia at all. The results indicate that hypotensive anesthesia induced by PGE1 and sevoflurane is a safe and a reliable method for neuroanesthesia. PMID- 1608153 TI - [The effects of induced hypotension with sevoflurane and PGE1 on liver functions during neurosurgery]. AB - The effects of induced hypotension with sevoflurane and PGE1 (Group S) on liver functions during neurosurgery that can avoid direct invasion of the liver were retrospectively studied in 35 cases, in comparison with 8 cases of isoflurane and PGE1 induced hypotension (Group I). GOT, GPT and gamma-GTP increased slightly in both groups 1 day and 1 week after operation, but they returned to preoperative levels 1 month later. ChE decreased in both groups, and the decrease was greater in group S. Three cases in Group S (8.6%) and one case in Group I (12.5%) showed GOT or GPT over 100 and there was no significant difference in the two groups. Hypotensive anaesthesia induced with sevoflurane and PGE1 in neurosurgery, as that induced with isoflurane and PGE1, has little effect on postoperative liver functions. PMID- 1608154 TI - [Pharmacokinetics of epidurally administered bupivacaine during prostaglandin E1- or trimetaphan-induced hypotension]. AB - The effects of prostaglandin E1 (PGE1) and trimetaphan (TMP) on the plasma concentrations and derived pharmacokinetic parameters of bupivacaine were studied in 14 women after its epidural administration. Patients, whose ages ranging from 35 to 60 years for mastectomy, received 50 mg of bupivacaine without epinephrine injected into the cervical epidural space during PGE1- or TMP-induced hypotension (80-90 mmHg of the systolic arterial pressure) under general anesthesia with nitrous oxide, oxygen and isoflurane 0.3-0.5%. No significant differences in pharmacokinetic parameters for the absorption and distribution of bupivacaine were found between the two groups. However, the mean elimination half-life of bupivacaine was significantly longer in patients with TMP [5.0 +/- 1.7 (SD) hr] compared with those with PGE1 (3.1 +/- 1.4 hr). The total clearance of bupivacaine was greater in patients with PGE1 (345 +/- 150 ml.min-1) compared with those with TMP (248 +/- 66 ml.min-1). The results of this pharmacokinetic study indicate that the plasma bupivacaine concentration decreases more rapidly during PGE1-induced hypotension than during TMP-induced hypotension. PMID- 1608155 TI - [Effects of hypotensive anesthesia with prostaglandin E1 or trimethaphan on renal microstructure]. AB - A study was made on the presence or absence and the degree of histopathological renal cell damage, in hypotensive anesthesia models with prostaglandin E1 (PGE1) or trimethaphan. Cell damage was most noticeable in the S3 segment, the straight and second half part of the proximal renal tubule. The lesion was evaluated and semiquantified. The trimethaphan group in this area exhibited degeneration- including cell vacuolation and granule increase in this site, as well as cytoclasis such as cell fragments in the lumen, luminal extension, flattening of epithelial cell and damage of distal renal tubular columns. In the PGE1 group, cell degeneration was milder than in the trimethaphan group, and there were no cytoclasis findings. Renal cell damage in the PGE1 group was slighter than in the trimethaphan group. PMID- 1608156 TI - [Clinical evaluation of prostaglandin E1 during anesthesia in non-elderly and elderly patients]. AB - The effects of prostaglandin E1 (PGE1) on blood pressure during anesthesia and the postoperative changes in organ functions were examined and compared in 358 cases. Two hundred and eighty patients were under 64 years of age and 128 patients were over 65 years. It was possible to control blood pressure satisfactorily with PGE1 in both non-elderly and elderly groups. However in the elderly group, it was more difficult to control blood pressure with PGE1 under NLA as compared with enflurane anesthesia. In both groups, urinary flow increased during and after the administration of PGE1, and the livers and kidneys showed neither dysfunction nor deterioration after operation. We had very few incidences of side effects with this drug. PGE1 is also considered safe and useful for elderly people during and after surgery. PMID- 1608157 TI - [Electroencephalographic change during induction of high-dose fentanyl anesthesia -evaluation by LIFESCAN EEG monitor]. AB - The relation between the patient's consciousness level and the change in electroencephalographic (EEG) activity during general anesthesia has not been well understood. In the present study, we evaluated such relationship quantitatively during the induction of high-dose fentanyl anesthesia in adult open-heart cases. There are significant increase in delta activity and significant decrease in alpha and beta activity in response to the induction of anesthesia. The loss of consciousness coincided with the sharp reduction in delta ratio and edge frequency (80%). Such reduction was more prominent in delta ratio than in edge frequency. These findings suggest that delta ratio could indicate the consciousness level during the induction of high-dose fentanyl anesthesia. Further study is needed to clarify the EEG response during inhalation and intravenous anesthesia in relation to EEG activity. PMID- 1608158 TI - [Influence of calcium channel blockers and beta-blockers on pain relief with iontophoresis]. AB - We studied usefulness of iontophoresis on pain relief using several Ca channel blockers, propranolol and guanethidine. Subjects were 18 healthy adult volunteers. We used 4% lidocaine with/without several drugs (2 mg of nicardipine, verapamil, diltiazem, propranolol and 10mg of guanethidine), and evaluated the pain relief effect with Nakahama's algesimeter. In all groups except for propranolol group, the pain recognition time was elongated significantly in comparison with control. In making comparison between each Ca channel blocker, we did not observe any significant differences, but, in propranolol group, elongation of pain threshold time was observed in some subjects. During these processes, systemic blood pressure and heart rate showed no remarkable changes. Our results suggest that it is possible to achieve more prolonged analgesic effect by the Ca channel blockers. PMID- 1608159 TI - [Effect of botulinum A toxin injection in the management of hemifacial spasm]. AB - The present study was carried out on the effect of botulinum A toxin, made in Japan, in the management of 30 hemifacial spasm patients. In almost all cases, alleviation of hemifacial spasm reached its peak in a few days. Availability was 93.3% and its effect lasted about 4 months. Side effects were observed in 12 patients (40%), but no serious complications were observed. PMID- 1608160 TI - [Effects of endotracheal intubation on the trachea--usefulness of the evaluation by MRI]. AB - Using an MRI apparatus, we observed the effects of endotracheal intubation on the trachea by measuring T1 value before and after an operation in ten surgical cases. T1 value of the anterior wall at the level of the first tracheal ring was 275.8 +/- 58 msec, and that of the posterior wall was 346.8 +/- 72 msec. The patients were all intubated under general anesthesia. Anesthesia was maintained with inhalation anesthesia such as nitrous oxide-oxygen-enflurane with the aid of vecuronium bromide. Periods of intubation varied between 80 to 46 minutes, and averaged 270 +/- 112 minutes. After the extubation, T1 value showed 312 +/- 62 msec at the anterior wall and 395 +/- 82 msec at the posterior wall. In the case of the posterior wall, T1 value was significantly prolonged compared with that of the pre-intubation period. Prolongation of T1 value is assumed to be related to the increase of tissue free water demonstrating the occurrence of tissue edema. From the findings that T1 value might be prolonged by endotracheal intubation, we conclude that the MRI apparatus is useful for investigating the effects of the intubation procedure on the trachea. PMID- 1608161 TI - [Significance of the measurement of arterial ketone bodies during abdominal surgery]. AB - Ketone body (3-hydroxy butyric acid) present in the blood was successively examined during surgical operations to ascertain the condition of energy metabolism and its clinical significance. In 10 patients (R group) to whom only the lactated Ringer's solution was infused during the operation, values of 3 hydroxy butyric acid increased remarkably in the 30 minutes after the operation began. In 7 patients (GI group), to whom the lactated Ringer's solution in 5% of glucose was administered, the values also increased in the 30 minutes after the operation was started. However, after the administration of glucose the values decreased, and returned to the normal value with administration of insulin. Furthermore, blood sugar readings which were examined at the same time increased significantly immediately after the beginning of the operation in both groups. Insulin readings showed considerably low values during the operation in R group. The readings of free fatty acid tended to show high values in R group, while they tended to decrease after the dose of glucose in GI group. With regard to epinephrine and norepinephrine readings, both groups showed significantly high values 30 minutes after the start of operation. PMID- 1608162 TI - [Drug-induced psychiatric disturbance by lidocaine]. AB - Lidocaine is widely used as an antiarrhythmic agent. One of the side effects of lidocaine is disorientation. Measurement was made of the plasma level of lidocaine in twelve consecutive cases. Lidocaine infusion had been given to these cases for more than twenty-four hours. Measurements were then made of the frequency of psychiatric disturbance. Psychiatric disturbances were recognised in six cases and the plasma levels in four cases among them were more than 5 micrograms.ml-1. The psychiatric disturbances disappeared within three hours after the cessation of lidocaine infusion. When disorientation occurs in a patient who receives lidocaine treatment, drug-induced psychiatric disturbance should be suspected. PMID- 1608163 TI - [Anesthetic management of a patient with diffuse pulmonary hamartoangiomyomatosis associated with spontaneous pneumothorax]. AB - We reported successful anesthetic management of a 34 year-old woman with diffuse pulmonary hamartoangiomyomatosis associated with spontaneous pneumothorax. She had recurrent pneumothorax and chest X-ray film showed reticulo-granular shadow, and chest CT revealed multiple bullae. Induced by thiopental and succinylcholine, anesthesia was maintained safely with enflurane in oxygen. Nitrous oxide was used after thoracotomy. This disease accompanies multiple bullae in the lung and some patients have complications such as tuberous sclerosis or hemangioma of the kidney. Therefore, we have to pay attention to both bullae and other complications. PMID- 1608164 TI - [A death caused by fulminant B-hepatitis which was latent preoperatively]. AB - It is not always easy to evaluate the preoperative liver functions exactly. In this paper we report a patient who died of fulminant hepatitis postoperatively in spite of careful examination of preoperative liver functions. A 60-year-old male had severe bleeding following total cystectomy, resulting in cardiac arrest. He was resuscitated successfully but developed multiple organ failure. He came through it but thereafter he had repeated infectious episodes from uretero cutaneous fistula and fluctuation of liver functions. Seven months later he had repair of postoperative ventral hernia. His liver functions were within normal limits except for positive HBs antigen. But eventually the patient died of acute fulminant transfusion hepatitis B 30 days after the operation. A cause of his death was, we presume, loading stress of surgical operation on the acute stage of hepatitis B. Other possible causes or deteriorating factors were drug liver injury, alcoholic chronic hepatitis, and coincidence of non A-non B hepatitis. When HBs antigen is positive in spite of normal liver function test, differential diagnosis between asymptomatic carrier and the first stage of acute hepatitis B should be made carefully. PMID- 1608165 TI - [Pneumonia due to aspiration of povidone-iodine during anesthesia--a case report]. AB - We report a case of pneumonia secondary to aspiration of povidone-iodine, which was used as an oral antiseptic. The patient was 17 y.o. female (body weight: 70 kg) who underwent a transsphenoidal resection of pituitary adenoma. Although she had a history of asthma during her childhood, no asthmatic attacks occurred for the past 10 yrs. After satisfactory anesthesia induction and tracheal intubation, 60 ml of 0.7% povidone-iodine solution was used to clean the oral cavity by a surgeon. Insufficient sealing by the cuff occurred after suturing the tube, which had made a needle hole in the cuff. Arterial oxygen saturation dropped to 90% and an increased resistance in the lungs was noted. The trachea was reintubated and she was transferred to the ICU. Her chest X-ray revealed signs of pneumonia and atelectasis in the right upper lobe. Mechanical ventilation with PEEP and periodical bronchial toilet were performed during her stay in the ICU for 42 hrs. A week was needed for the improvement of her X-ray findings. Although povidone iodine is thought to be safe and affective antiseptics, severe complications from its aspiration may occur in patients whose airways are sensitive as observed in this case. PMID- 1608166 TI - [A beneficial effect of glucose-insulin-potassium infusion for intractable ventricular fibrillation--a case of intraoperative myocardial infarction]. AB - A 61-year-old man suffering from compression fracture of the first lumbar vertebra was scheduled for anterior and posterior spinal fusion. Anesthesia was maintained with enflurane, nitrous oxide in oxygen and fentanyl. When his position was changed from right lateral to supine position, ventricular fibrillation (VF) occurred. The operation was discontinued and he was taken into ICU receiving cardiopulmonary resuscitation. Despite ordinary therapies including DC-shock and lidocaine infusion, Vf and defibrillation recurred more than 20 times for the first two hours. Electrocardiogram showed elevation of ST-T segments in II, III, aVF and V1-V3 leads. Because no effective treatment was found, we attempted to use glucose-insulin-potassium mixture, by which Vf stopped. Electrocardiogram taken on the following day showed abnormal Q wave in II, III and aVF leads, and the patient was diagnosed as having had acute myocardial infarction. On the fifth postoperative day, the patient was returned to the ward without neurological deficits. We conclude that glucose-insulin potassium infusion is a beneficial therapy for Vf, which is resistant to ordinary treatments. PMID- 1608167 TI - [Anesthetic experience of two patients with holoprosencephaly]. AB - We experienced anesthetic management of two 6-month-old female patients with holoprosencephaly (HP). HP is characterized by hypoplasia of prosencephalon, facial anomalies (hypotelorism, flat nose, and/or small prolabium), abnormality of autonomic nervous system functions (hypernatremia and/or poikilothermia), and clonic convulsion. First case was a lobar type and the second case was an alobar type according to DeMyer's classification. In both cases repair of bilateral cleft lip was performed. Anesthesia was slowly induced with N2O-O2-halothane and maintained with fentanyl in N2O-O2. Body temperature (BT) was adjusted with a warming blanket while monitoring rectal temperature. In the first case clonic convulsion and bradycardias occurred during the postoperative period, which were treated with IV diazepam and isoproterenol. In the second case BT rose to 39 degrees C during postoperative period; 2 episodes of convulsions were observed; and airway obstruction occurred. They were treated accordingly. The most important points which should be kept in mind in the management of HP patients are the prevention of convulsion, adjustment of BT, maintenance of normal pulse rate and keeping a patient airway. PMID- 1608168 TI - [Anesthetic management for partial tongue resection in a patient with Beckwith Wiedemann syndrome]. AB - A 14-month-old baby weighing 4300 g was a giant infant with macroglossia. Exomphalos was not present, but diastasis recti abdominis was observed. The patient was therefore diagnosed as having Beckwith-Wiedemann syndrome (EMG syndrome). Other characteristic signs such as neonatal hypoglycemia, hemihypertrophy, and a small ventricular septal defect were also recognized, but nephromegaly or hepatomegaly was not present. Tongue reduction by wedge resection was performed under general anesthesia. Some of the problems associated with anesthetic management in this syndrome are hypoglycemia, airway obstruction and cardiovascular status. After induction with increasing concentration of halothane (0.5-4.0%) and 66% nitrous oxide in oxygen, a nasotracheal tube was inserted. Endotracheal intubation was easy without using a neuromuscular blocking agent. Anesthetic maintenance was accomplished with nitrous oxide 66% in oxygen and halothane 0.5-1.0% and no neuromuscular blocking agent was used. The plasma glucose level was kept within normal ranges during and after the operation by infusion of acetate Ringer's solution with 5% glucose. The postoperative progress was uneventful. PMID- 1608169 TI - [A new parking cart for Selectatec vaporizers]. AB - The author designed a cart which can safely carry and accommodate Selectatec vaporizers (Ohmeda). The cart consists of ten parking brackets on which Selectatec vaporizers can be mounted and their support arms with castors. An anesthetic machine which has a Selectatec manifold allows easy removal and replacement of vaporizers, but there are several troublesome regulations regarding conveyance and accommodation of vaporizers. By the use of the cart, all these problems were completely solved and the advantage of the centralization of many vaporizers was accomplished. PMID- 1608171 TI - [Regulation system of ADP-ribosyltransferase activity of cholera toxin by protein factors]. PMID- 1608170 TI - [Role of microorganisms and their substances for pathogenesis of arthritis as an autoimmune disease]. PMID- 1608172 TI - [Affinities of PBPs of enterococci to cefepime and ampicillin]. AB - The beta-lactam resistance of genus Streptococcus has been explained by the low binding affinity of penicillin-binding proteins (PBPs) to the drug. This study was carried out to resolve the mechanisms of resistance to beta-lactam antibiotics in the species of genus Enterococcus by means of binding affinities of PBPs. Streptococcus pyogenes, Enterococcus faecalis, Enterococcus faecium and Enterococcus avium were employed as assay microbes. Cefepime (CFPM) and ampicillin (ABPC) were used as representatives of cephems and penicillins, respectively. All the PBP fractions of S. pyogenes manifested high binding affinities to CFPM and ABPC, whereas PBPs 1 and 4 of E. faecalis showed high binding affinities to ABPC but not to CFPM. In E. faecium, PBPs of an exceptionally penicillin-susceptible strain manifested a high binding affinity to ABPC, but PBPs 5 and 6 showed low affinities to CFPM. beta-lactam resistant strains of E. faecium possessed PBPs 5 and 6 with low binding affinities to CFPM and ABPC. All the fractions of PBPs but PBP 1 in E. avium showed low binding affinities to CFPM. Although all the PBP fractions but PBPs 3 and 6 manifested high binding affinities to ABPC, PBPs 3 and 6 showed low binding affinities to ABPC. A strain of E. avium, which is susceptible to ABPC but moderately resistant to CFPM, lacked PBP 6. In conclusion, the resistance of E. avium to CFPM is based upon low binding affinities of the many fractions to this drug, and ABPC resistance is based upon PBPs 3 and 6 with low binding affinities to ABPC. PMID- 1608173 TI - [Methods for detecting the protein phosphorylation in cells stimulated with extracellular stimuli]. PMID- 1608174 TI - [Quality of life studies in nursing science (1). Quality of life studies in cardiovascular diseases]. PMID- 1608175 TI - [Quality of life studies in nursing science (1). Development of a quality of life index for patients]. PMID- 1608176 TI - [Quality of life studies in nursing science (1). Family stress coping caused by cancer patients who are receiving chemotherapy and not informed of the diagnosis]. PMID- 1608177 TI - [Quality of life studies in nursing science (1). Community adjustment of chronic schizophrenics: effects on life satisfaction and self-esteem (1)]. PMID- 1608178 TI - [Quality of life studies in nursing science (1). The concept and scale of QOL in nursing science: review from two research projects by RNs]. PMID- 1608179 TI - [Quality of life studies in nursing science (1). The descriptive study of quality of life among men in living with chronic ischemic heart disease: analysis on the aspects of daily life control and sexuality (2)]. PMID- 1608180 TI - [Quality of life studies in nursing science (1). Quality of life: the conceptual aspects]. PMID- 1608181 TI - [Examination of the usefulness of echocardiography with dobutamine for diagnosis of coronary disease]. AB - To assess the feasibility, safety and usefulness of dobutamine stress echocardiography for the detection of coronary artery disease we evaluated 63 patients (45 men, 18 women) with effort chest pain. All patients underwent electrocardiographic submaximal bicycle exercise testing and 2-dimensional echocardiography during dobutamine infusion. Echocardiographic dobutamine test response was considered positive when new wall motion abnormalities were observed during dobutamine infusion. Sensitivity and specificity of electrocardiographic exercise test and dobutamine stress echocardiography were assessed in 25 patients who underwent selective coronary angiography. The sensitivity and specificity of dobutamine stress echocardiography, respectively 93.3% and 83.3%, were higher than those of exercise electrocardiography. 2-dimensional echocardiography during dobutamine infusion is a well tolerated, feasible and effective test for detecting coronary artery disease. PMID- 1608182 TI - [Clinical and electrophysiological indications for surgical treatment in patients with Wolff-Parkinson-White syndrome]. AB - 20 patients with WPW syndrome and recurrent tachyarrhythmias were studied clinically and electrophysiologically. The localization and electrophysiological properties of accessory pathways and other heart structures were estimated before the surgical treatment. 13 patients (pts) suffered syncope in the course of atrial flutter or atrial fibrillation with heart rate greater than 300/min, often proceeding into ventricular fibrillation or atrioventricular tachycardia greater than 260/min, which sometimes proceeds into atrial/ventricular fibrillation. 6 pts experienced dizziness or fainted during tachyarrhythmias or rhythm changes. In 15 pts antiarrhythmic drugs in monotherapy or various combinations did not prevent recurrence of tachyarrhythmias. In 4 of 5 other pts only amiodarone was effective but the drug was discontinued due to serious adverse effects. The lack of good effect of antiarrhythmic drug therapy can be based on mutually unfavorable electrophysiologic properties of the accessory pathways and other heart structures. Pts who experienced syncope had a particularly short effective refractory period (ERP) of the accessory pathways in ante- and retro-grade direction and short ERP of the ventricle muscle. Additionally, there were multiple accessory pathways, heart muscle impairement and frequent ventricular premature beats--factors triggering the tachyarrhythmias. PMID- 1608183 TI - [Results of allogenic and autologous bone marrow transplantation in children with acute myeloid leukemia]. AB - We report on our experience of bone marrow transplantation (BMT) in children with acute myeloblastic leukaemia (AML) and high risk of relapse (initial WBC greater than 20 x 10(9)/l, FAB M 5, M 6, M 7). 32 children were grafted between november 1982 and october 1991 at the Children's Hospital of the University of Jena. Two patients underwent an allogenous BMT in relapse and died from progressive disease. In 13 children an allogeneic BMT was performed in first complete remission. One patient relapsed, two patients died from severe acute graft-versus host disease, and two patients died from encephalopathy and cardiomyopathy. Eight of the 13 patients are living and well 18 months to eight and a half year after BMT. Seventeen patients received an autologous (unpurged) BMT. Four of them relapsed four to seven months after BMT. The disease free survival (DFS) for the 29 patients grafted in remission was 0.65. There was no statistical significant difference in DFS between patients with allogeneic and autologous BMT. We conclude that in children with AML and high risk for relapse BMT offers a real chance for better survival. Autologous BMT avoids the problems of graft-versus host disease and of finding suitable donors for allogeneic marrow transplantation. PMID- 1608184 TI - [Intracerebral hemorrhage and its sequelae in high risk newborn infants in relation to oxygen deficiency status]. AB - In a prospective study 325 risk newborn infants were examined by means of ultrasound scanning. Children with and without intracerebral haemorrhages were classified, according to pre-, intra-, and postnatal periods of oxygen privation. For the characterization of short-term hypoxia the blood-gas analysis was used for the ascertainment of longtime hypoxia the erythrocytic-density-test (EDT). In dependence on PO2-values less than or equal to 5 kPa intracerebral haemorrhages of variable states increased significantly (p = 0.01). Evaluating the results of erythrocytic-density-test it may be concluded that the prenatal hypoxia has the greatest influence on the rate of intracerebral bleedings. Thus only 37.5% of our patients with prenatal hypoxia remained free of haemorrhages, in contrast of 70.2% of children without deficiency of oxygen. PMID- 1608185 TI - [The pathogen spectrum and its resistance behavior in children with urinary tract infections in Angola]. AB - In 225 children (135 boys, 90 girls) suffering from clinical relevant urinary tract infection the bacterial spectrum and resistance behaviour to routinely used antibiotics were evaluated. In 65.4% of the patients a significant bacteriuria was found: E. coli (34.6%), proteus (22.3%), klebsiella (14.6%), citrobacter (9.2%), enterobacter (5.4%) and pseudomonas (5.4%). In testing a high resistance of bacterias to trimethoprim/sulfamethoxazol, ampicillin, and gentamycin was found, whereas good susceptibility was found to nitrofurantoin and nalidixin acid. PMID- 1608186 TI - [The status of hemoglobin concentration and hematocrit in Angola children]. AB - Hemoglobin-concentration (Hb) and hematocrit (Ht) were determined in 622 Angolean children between ages of 3 months and 13 years. The children were divided into two groups: group I (n = 530) of low social and economic state, group II (n = 92) children enjoyed good living conditions. 38.9% of all children had a Hb below 6.8mmol/l. 218 of which were part of group I, only 18 were out of group II. An extensive anemia (less than Hb 4.3mmol/l) existed in only 3% of all children. 51.7% of children were below 3 years. Between age groups of 3 months to over 10 years there was a continual rise in Hb of 17.6 +/- 6.6% (boys) and 9.5 +/- 3% (girls). Using the Ht values the percentage of anemic children was only 16.4%. It existed a relationship, especially, clearly observed in group I, between physical development and aemia frequency. Children of group I were more anemic than children of group II. PMID- 1608187 TI - [Capillary blood as diagnostic sample in pediatric laboratory diagnosis. Arterio capillary-venous difference and blood collection technique]. AB - It is preferable to use capillary blood as diagnostic material in paediatric laboratory tests rather than venous blood. The collection of capillary blood makes less demands on the child and is easy in principle. The objection to capillary blood primarily concerns differences in the analyte concentration in arterial, capillary and venous blood. Comparative studies in the same child under standardised conditions are not available for a number of parameters. However, according to the results available at present, for almost all routine clinical chemical and haematological examinations clinically usable results can be obtained. Using the example of total protein analysis for the same child we did not find any differences between arterial and venous blood. It is highly probably that the same would apply to many other components. Suspected differences are probably a result of short-comings in the collection technique. PMID- 1608188 TI - [Historical observations on nomination for faculty chairs in pediatrics]. PMID- 1608189 TI - [30th Annual Meeting of the European Society of Pediatric Endocrinology 25 to 28 August 1991 in Berlin]. PMID- 1608190 TI - [Anti-infectious immunity and bacteriuria in patients with the nephrotic syndrome]. AB - The study was made of antiviral antibodies to respiratory viruses, mycoplasma, O streptolysin, of qualitative and quantitative characteristics of bacteriuria in 52 patients with nephrotic syndrome (NS) due to glomerulonephritis against 18 NS control subjects without glomerulonephritis. Significant differences between the groups appeared in the titers of antibodies to Coxsackie and influenza A viruses. O-streptolysin. Persistence of viral latent infection in NS is suggested as well as a trigger role of viruses in the disease onset and that of other urinary inflammatory affections whose incidence is now on the increase. PMID- 1608191 TI - [Disorders of the protein-transport function of the intestines in chronic kidney diseases]. AB - Radioactive albumin studies were performed in patients with chronic renal disorders. The findings evidence an essential decline of intestinal protein transport function, enhanced catabolism, impairment of protein synthesis and its renal loss which underlie protein deficiency. PMID- 1608192 TI - [Circadian rhythm parameters of partial kidney functions in chronic glomerulonephritis]. PMID- 1608193 TI - [A case of managing ventricular tachycardia with sombrevin]. PMID- 1608194 TI - [A combination of kidney cancer and carbuncle]. PMID- 1608195 TI - [Industrial medical expertise in Rendu-Osler disease]. PMID- 1608196 TI - [The pharmacotherapy of chronic glomerulonephritis]. PMID- 1608197 TI - [On the centenary of the birth of Sergei Sergeevich Iudin]. PMID- 1608198 TI - [The reflection of medical problems in the Caucasian works of L. N. Tolstoi (on the 140th anniversary of the writer's arrival in the Caucasus)]. PMID- 1608199 TI - [The effect of calcium antagonists on carbohydrate metabolism]. PMID- 1608200 TI - [Partial ileal shunting in the treatment of hyperlipoproteinemia]. PMID- 1608201 TI - [The clinico-pathogenetic characteristics of Kaposi's sarcoma]. AB - The paper is concerned with clinicomorphological characteristics of endemic, immune and epidemic (AIDS-associated) forms of Kaposi's sarcoma (KS). Recent experimental and clinical evidence suggests pathogenic contribution to KS of virus-induced depression of sex-linked genes and immunosuppression. Combined action of these factors should be regarded when specifying current presentation of KS. PMID- 1608202 TI - [The prognostic significance of changes in the level of natural antibodies to thrombin in stenocardia patients]. AB - Coagulation in angina pectoris has been analyzed in a normal and elevated level of natural antibodies (nAb) to thrombin. A correlation was found between the level of nAb to thrombin and hemostatic shifts. The correlation of a nAb rise was attempted by means of plasmapheresis (PA) or plasmosorption (PS), altering coagulation potential. PA and PS produced more pronounced anticoagulative effects in patients with a normal baseline level of nAb to thrombin. When the latter levels tended to reduction from initially high, hemostatic processes improved. It is concluded that nAb to thrombin levels have prognostic potential as an indicator of coagulation activity and efficacy of anticoagulant therapy in extracorporeal interventions. PMID- 1608203 TI - [The prospective evolution of the efficacy of antiarrhythmia therapy in paroxysmal supraventricular tachycardia in patients with the ventricular pre excitation syndrome]. AB - Evolution of the effectiveness of antiarrhythmic drugs used in 240 patients with preexcitation syndrome to arrest episodes of paroxysmal supraventricular tachycardia was analysed prospectively. The first intravenous administration was effective in 97, 93.3, 80.9, 75, 70.3, 60, 48% of cases for novocainamid, verapamil, cordarone, disopyramide, ajmaline, ethacizine, mexitil and inderal, respectively. When observed in prospective evolution for 10-14 years, overall group efficacy dropped from 81.3% at first administration to 21.4%. PMID- 1608204 TI - [Methodological bases for prognosis in medicine]. AB - Current status of prognosis in clinical, experimental and prophylactic medicine is delineated with formulation of the purposes and feasibility of therapeutic and preventive realization of the disease onset and run prediction. Literature and first-hand experience provided the basis for grounding medical prognosis theory. Basic points in the theory are the following: utilization in the prognosis of only a complex of the most significant clinical signs of the disease, the patient's record, social and household, ecological and occupational aspects of the patient's life; comparison of the latter with leading pathogenetic mechanisms underlying the emergence and progression of the pathology; consideration of the relationships between dysfunction and morphology of the organs and systems; simultaneous analysis of the aggression factors, systemic reactivity and resistance of tissue; scrutiny of predisposition to pathological reactions. An essential aspect of medical prediction is a valid choice of mathematical methods of analysis and processing of the clinical information. PMID- 1608205 TI - [The function of the heart ventricles in patients with a lesion of the aortic arch branches]. AB - Radionuclide equilibrium ventriculography was used to examine general and regional ejection fractions and velocity characteristics for both cardiac ventricles in 28 patients with occlusions of the aortic arch branches consequent to aortic arteritis of atherosclerosis. In nonspecific aortic arteritis (NAA) even young patients have myocardial dysfunction comparable to that in the elderly with atherosclerosis. However, as shown by the nitroglycerin test, these patients preserve functional reserves of the myocardium. Right ventricular hyperfunction observed in NAA patients may result from increased postload due to possible hypertension. The above myocardial shifts should be considered when deciding on reconstructive surgery on the aortic arch branches. PMID- 1608206 TI - [The internal picture of the disease in subjects with a history of a heart valve prosthetic operation under artificial circulation]. AB - Sensitive, emotional, intellectual, motivation, preoperative and postoperative aspects of the disease pattern were studied in 93 patients who had acquired valvular defects and underwent replacement of the valves in conditions of artificial circulation. The findings provided evidence in support of psychic correction for preoperative preparation of the patients and postoperative restoration of their personality and social status. PMID- 1608207 TI - [Infectious endocarditis of the right heart]. PMID- 1608208 TI - [The Doppler sonographic measurement of the blood flow in the portal vein system in portal hypertension]. AB - Diagnostic potentialities of Doppler sonography in assessment of portal hemodynamics in patients with chronic active hepatitis and hepatic cirrhosis were compared to those of noninvasive (rheohepatography) and invasive (angiography) techniques. Dopplerograms of the portal vein and its branches are described in specific details. Meals and treatment with beta-adrenoblockers reducing portal hypertension are evaluated in relation to their influence on the portal hepatic circulation. PMID- 1608209 TI - [The information value of diagnosing myocardial infarct by blood density at the prehospital stage]. AB - Basing on the clinical evidence, a comparative study was made of a diagnostic significance of ECG, biochemical findings and blood density in myocardial infarction. Unlike the former two criteria, changes in blood density allowed the clinicians to detect irreversible lesions in the myocardium. The method has advantages in prehospital diagnosis of the infarction as its efficacy at the very onset of the disease is superior to that of ECG. In view of blood density diagnosis of myocardial infarction convenience for practical use, reproducibility, ability to provide information when routine modalities fail to determine the ischemic myocardial lesion, it can be introduced as an adjuvant diagnostic means for cardiologic and common emergency teams. PMID- 1608210 TI - [The cardiac activity in patients with liver cirrhosis based on the data from 24 hour ECG monitoring]. AB - 24-h ECG monitoring was performed in healthy subjects and patients with hepatic cirrhosis. Abnormalities rare in healthy individuals and frequent in the patients were registered. Cirrhosis patients presented marked changes in time parameters of cardiac performance. PMID- 1608211 TI - [A comparative evaluation of sorbents in performing hemosorption on bronchial asthma patients]. PMID- 1608212 TI - [A course of nitrong use in the combined treatment and hospital rehabilitation of patients with chronic cor pulmonale]. PMID- 1608213 TI - [The effect of the combined use of hemosorption and plasmapheresis on the blood rheological and hemodynamic indices of hypertension patients]. AB - Basing on the response obtained in 46 patients with stage II essential hypertension, the conclusion is made on a positive action of hemosorption plus plasmapheresis on blood rheology, hemodynamics, clinical course of hypertension. The response persisted for up to 6 months. PMID- 1608214 TI - [The effect of hypoglycemic therapy on atherogenesis in diabetic patients]. AB - Lipid blood fractions, malonic dialdehyde and antioxidant activity of plasma and red blood cells were evaluated in 56 patients with type I diabetes mellitus. Twenty-three of those had coronary heart disease. It was established that, if the patients received mean doses of insulin 80.5 +/- 2.70 U/day, they had higher levels of cholesterol, triglycerides and VLDL cholesterol than those who were treated with insulin in a dose of 43.2 +/- 1.84 U/day. PMID- 1608215 TI - [Psychosomatic disorders in patients with neurocirculatory dystonia and their correction in the day hospital]. AB - Clinical and psychological tests were used to examine 77, 31 and 32 patients with normotonic, hypertonic and hypotonic neurocirculatory asthenia, respectively. Compared to control subjects, 80% of the patients responded to stress with psychic and social dysadaptation (psychic asthenia, frustration, emotional lability, hypothymism) as well as depression with visceral manifestations: cardialgia, extrasystole, lability of arterial pressure. Chemotherapy, physical and psychological treatment in day hospital produced a response in 89.2% of neurocirculatory asthenia sufferers. PMID- 1608216 TI - [The efficacy of lincomycin in tick-borne encephalitis]. AB - Lincomycin was found to inhibit tick-borne encephalitis (TBE) virus. To test antiviral potential of this drug, a clinical trial was initiated entering TBE patients from known focuses of the disease (Novosibirsk, Kemerovo, Perm and Irkutsk Provinces). The drug was given to 23 patients with meningeal and meningoencephalitic TBE. A control group of 22 matched subjects received specific immunoglobulin. Resultant efficacy of lincomycin appeared not inferior to that of anti-TBE immunoglobulin. Lincomycin can be successfully introduced in the treatment of meningeal and meningoencephalitic TBE. PMID- 1608217 TI - [Viral hepatitis A and the possible pathogenetic mechanisms of a protracted convalescence]. AB - Metabolites of connective tissue (free serum oxyproline, protein-bound plasma oxyproline, total urine oxyproline, serum glycosaminoglycans), proteolytic enzyme elastase, proteolysis inhibitors (alpha 1-inhibitor, alpha 2-macroglobulin) were investigated in 103 patients with viral hepatitis A. It was established that connective tissue and its metabolites produce a negative effect on hepatocytic repair. Longterm convalescence is attributed to elastase hyperactivity in the presence of relative deficiency of proteolytic inhibitors. PMID- 1608218 TI - [The use of water-soluble vitamins in viral hepatitis A]. AB - To correct disbolism of vitamins C, B3, B6 and B12 due to viral hepatitis A (VHA), the patients received daily doses of the vitamins: 300 and 400 mg of ascorbic acid, 300 and 600 mg of calcium pantothenate or 90 and 180 mg of pantetin per os. 100 and 200 micrograms of cyanocobalamin alternating with 50 and 100 mg of pyridoxin was given intramuscularly every other day. The course lasted 3-4 weeks. The vitamin treatment promoted a positive trend in clinico-biochemical parameters, normalization of immunocompetent cell and serum immunoglobulins levels, of phagocytic reaction of peripheral blood neutrophils. PMID- 1608219 TI - [Lipostabil in the treatment of viral hepatitis B in subjects who abuse alcohol]. AB - A trial was conducted of clinical efficacy of lipostabil. Twenty-three lipostabil treated patients with hepatis B abusing alcohol were compared to a control group receiving standard treatment. Lipostabil has advantages as it shortens jaundice, cholestasis, enhances recovery of lipid metabolism in erythrocytic membranes and antioxidant properties of blood. Lipostabil holds promise in multimodality treatment of combined hepatic lesions. PMID- 1608220 TI - [The clinical significance of the C3 component of complement in different variants of viral hepatitis B]. AB - Pathogenetic involvement of complement system was ascertained at examination of 259 patients with acute and chronic viral hepatitis B. In progression of acute hepatitis there exist close relationships between blood levels of C3 component and antigens, antibodies and homeostatic parameters. This proves complement participation in the antiviral defense and support of biochemical mechanisms responsible for recovery. Registration of C3 component content time course in acute and chronic viral hepatitis can serve prognostic purposes. PMID- 1608221 TI - [The development of a method for determining the quantity of 3 alpha- and 7 alpha bile acids in the feces]. PMID- 1608222 TI - [The efficacy of bioelectrostimulation in treating patients with burn injuries]. AB - The paper describes the data obtained by Soviet and American physicians who took part in the treatment of patients burnt in the Bashkiria accident (an outburst of petroleum products). It was established that in deep burns bioelectrostimulation combined with early necrectomy and autodermoplasty yielded the best therapeutic results. PMID- 1608223 TI - [The use of regional perfusion in treating patients with acute obstetrical gynecological sepsis]. PMID- 1608224 TI - [The current aspects of the diagnosis and treatment of primary hyperaldosteronism]. PMID- 1608225 TI - [Hyperbaric oxygenation in the combined therapy of infectious diseases]. AB - Hypoxia plays an important role in pathogenesis of infectious diseases. Therefore, its correction is an essential factor in pathogenetic antibacterial treatment. Hyperbaric oxygenation (HBO) as a leading method in current antihypoxic therapy was studied in combined medication for typhoid, diphtheria, meningococcal infection, viral hepatitis. HBO sessions were given to 331 patients, 363 controls did not receive HBO. Utilization of HBO provided much better saturation of blood with oxygen, eliminated metabolic disorders, warranted favorable course and outcomes of the diseases. PMID- 1608226 TI - [The characteristics of hematuria in chronic glomerulonephritis and nonglomerular diseases of the kidneys and urinary tract]. AB - Upon the analysis of qualitative and quantitative characteristics of hematuria in renal and urinary tract affections it was established that whatever the red blood cell count in the urine, hematuria is primarily glomerular in contrast to nonglomerular in chronic glomerulonephritis and nonglomerular diseases of the kidneys and urinary tracts, respectively. Morphologic studies of urinary red blood cells using phase-contrast microscopy proved a valuable tool for identification of hematuria origin. PMID- 1608227 TI - [Marketing as the beginning of a solution for health care. The patient as client. Interview by Fred Arm]. PMID- 1608228 TI - [Labor legislative principles. Protective laws]. PMID- 1608229 TI - [Successful group therapy with schizophrenic patients. The group is stabilizing]. PMID- 1608230 TI - [New rules for nursing education. Opening of limits]. PMID- 1608232 TI - [Out of the life of a community nurse. From men and beasts]. PMID- 1608231 TI - [Extended basic education in psychiatric nursing at the Zurich Burgholzli. Hospital walls are overcome]. PMID- 1608233 TI - [Exploring one's own limits. "Liberation means consciously moving around one's limits"]. PMID- 1608234 TI - [The introductory interview (II). Salary and informative interview]. PMID- 1608235 TI - [Multiple personalities. Looking for my lost self]. PMID- 1608237 TI - [Social barriers. Meeting the excluded]. PMID- 1608236 TI - [Nursing practice: borders or barriers? The courage to be oneself]. PMID- 1608238 TI - [We are mistaken in our definition of progress]. PMID- 1608239 TI - [And the natural barriers?]. PMID- 1608240 TI - Time-interval analysis of interjudge and intrajudge agreement for stuttering event judgments. AB - In response to the recognized need for a valid and reliable way to measure stuttering, this study investigates a measurement methodology based on time interval analyses of stuttering event judgments. Three groups of judges, differing in stuttering judgment experience, identified stuttering events in 12 repeated presentations of five 1-min speech samples. Fixed time intervals ranging from 0.2 sec to 7.0 sec were then superimposed on the event judgments by a data analysis program. Inter- and intrajudge interval-by-interval agreement, and agreement for total numbers of intervals containing stuttering event judgments, were calculated for each judge group. Results showed that agreement was superior among more experienced judges and in longer interval lengths. Agreement varied across speech samples but not across the repeated judgment opportunities. Agreement was maximized at greater than chance levels for an interval of approximately 3.0 sec, but even this best agreement did not exceed a mean of approximately 60% for experienced judges. PMID- 1608241 TI - Modifying electroglottograph-identified intervals of phonation: the effect on stuttering. AB - Single-subject experiments were conducted with an adolescent and an adult male who stutter to assess the effect on stuttering of changing the frequency of phonation intervals that were within prescribed duration ranges during spontaneous speech. Electroglottograph-identified intervals of phonation were measured using a computer-assisted biofeedback system. Both subjects demonstrated that their stuttering could be controlled by modifying the frequency of phonation intervals within short duration ranges. The experimental effects not only replicated earlier findings but were demonstrated to be independent of changes in speaking rate, or alterations to other intervals of phonation, and produced little disruption to speech naturalness. The theoretic implications of these findings are discussed. PMID- 1608242 TI - Individual differences in voice quality perception. AB - Sixteen listeners (10 expert, 6 naive) judged the dissimilarity of pairs of voices drawn from pathological and normal populations. Separate nonmetric multidimensional scaling solutions were calculated for each listener and voice set. The correlations between individual listeners' dissimilarity ratings were low. However, scaling solutions indicated that each subject judged the voices in a reliable, meaningful way. Listeners differed more from one another in their judgments of the pathological voices (which varied widely on a number of acoustic parameters) than they did for the normal voices (which formed a much more homogeneous set acoustically). The acoustic features listeners used to judge dissimilarity were predictable from the characteristics of the stimulus sets: only parameters that showed substantial variability were perceptually salient across listeners. These results are consistent with prototype models of voice perception. They suggest that traditional means of assessing listener reliability in voice perception tasks may not be appropriate, and highlight the importance of using explicit comparisons between stimuli when studying voice quality perception. PMID- 1608243 TI - Variability of acoustic segment durations after prolonged-speech treatment for stuttering. AB - Existing literature suggests that one of the effects of treatment based on prolonged speech is increased durations of acoustic segments. However, the external validity of the data concerned may be questioned because the data were not based on spontaneous speech samples and were gathered from subjects with unknown treatment histories. With this in mind, the present investigation used young clients with no history of treatment based on prolonged speech and obtained pretreatment and posttreatment acoustic measures from spontaneous speech samples. Acoustic measures showed no significant posttreatment increases in durations of acoustic segments. However, for the acoustic measure of vowel duration and a measure of articulation rate, posttreatment speech samples showed significantly reduced variability. The potential theoretical and practical relevance of these findings is discussed. PMID- 1608244 TI - The effects of noise masking and required accuracy on speech errors, disfluencies, and self-repairs. AB - The covert repair hypothesis views disfluencies as by-products of covert self repairs applied to internal speech errors. To test this hypothesis we examined effects of noise masking and accuracy emphasis on speech error, disfluency, and self-repair rates. Noise reduced the numbers of disfluencies and self-repairs but did not affect speech error rates significantly. With accuracy emphasis, speech error rates decreased considerably, but disfluency and self-repair rates did not. With respect to these findings, it is argued that subjects monitor errors with less scrutiny under noise and when accuracy of speaking is unimportant. Consequently, covert and overt repair tendencies drop, a fact that is reflected by changes in disfluency and self-repair rates relative to speech error rates. Self-repair occurrence may be additionally reduced under noise because the information available for error detection--that is, the auditory signal--has also decreased. A qualitative analysis of self-repair patterns revealed that phonemic errors were usually repaired immediately after their intrusion. PMID- 1608245 TI - Laryngeal paralyses: theoretical considerations and effects on laryngeal vibration. AB - The neurological causes of vocal fold paralyses have been well documented. However, the effect of these disorders on laryngeal vibration is not well understood. A theoretical four-mass model of the larynx, based on the work of Ishizaka and Isshiki (1976) and Koizumi, Taniguchi, and Hiromitsu (1987), was developed and adapted to simulate laryngeal biomechanical behavior. The model was used to evaluate various states of asymmetric laryngeal vibration. Input parameters that relate observed laryngeal function and model simulation were developed. Laryngeal paralyses were simulated by their predicted effect on these parameters. Simulations were compared with available data on glottal vibration in laryngeal paralyses. Complex modes of vibration were seen with certain combinations of asymmetrical lower mass stiffness and initial glottal gap. PMID- 1608246 TI - Brain blood flow related to acoustic laryngeal reaction time in adult developmental stutterers. AB - The 1980s witnessed renewed interest in the relation between developmental stuttering and central nervous system (CNS) abnormalities. We have reported differences between nonstutterers and developmental stutterers on electrophysiologic (QTE) and metabolic (rCBF) measures of brain function. A critical step in the interpretation of results of functional brain imaging studies is to determine the relation, if any, of identified CNS abnormalities to speech motor control in persons who stutter. In this study we addressed the interpretation of rCBF findings by asking whether we could identify patterns of impaired acoustic laryngeal reaction time (LRT) as a function of response complexity parallel to rCBF findings. Stutterer subgroups determined by clinical severity ratings were not differentiated by LRT values as a function of response complexity. Stutterers with relative blood flow asymmetry below the normal median value involving both left superior and middle temporal regions of interest (ROIs) showed significantly longer LRT for the complex response than did normal speakers and stutterers with above-normal median relative flow values to at least one of these temporal ROIs. Stutterer subgroups based on reduced cingulate flow alone were not differentiated by LRT values. Findings are consistent with Goldberg's (1985) model of CNS premotor processing. Findings also suggest that stutterer subgroups might be distinguished by the presence, loci, and relative magnitude of cortical and/or subcortical rCBF abnormality in regions that subserve a fluency generating system. PMID- 1608247 TI - Vocal tremor analysis with the Vocal Demodulator. AB - Acoustic analysis of vocal tremor has the potential to make significant quantitative and diagnostic contributions to the study of vocal disorders. This paper presents a new device for analysis of vocal tremor. The Vocal Demodulator produces amplitude- and frequency-demodulated outputs and measures the frequency and level (percent) of low-frequency tremor components in sustained phonation. A standard microphone is used to transduce the voice signal for input to the demodulator. The input fundamental frequency (F0) range is 70-1200 Hz, and frequency response of the amplitude and frequency demodulation is 2.5-25 Hz. Five parameters are displayed in real time: F0, amplitude-modulation frequency, amplitude-modulation level, frequency-modulation frequency, and frequency modulation level. Validation, calibration, and reliability data from synthesized test signals with modulation, as well as phonation from subjects with vocal tremor, subjects producing vibrato, and subjects with normal voice are presented. Research and clinical applications of this device are suggested. PMID- 1608248 TI - Spectral study of deviant resonance in the speech of women who are deaf. AB - In a previous radiographic study of 4 deaf women, some aberrant features in vocal tract configuration were identified for vowels produced with excessive pharyngeal resonance. These features included neutralization of tongue position, elevation of the hyoid, and a retraction of the tongue, associated with a deflection of the epiglottis in the lower pharynx. The vowels, produced simultaneously with X-ray exposure, were analyzed spectrographically to study acoustic correlates of the vocal tract deformation. Comparisons of the formants for vowels /i/ /u/ and /a/ produced by the deaf women with mean formant values for these vowels produced by normal-hearing women revealed no consistent pattern of second-formant deviation. Formant structure evaluated on isovowel lines disclosed consistent neutralization of vowels, with F2 values clustering in the 1500-2100 Hz frequency range, which is attributed to the observed restricted horizontal movements of the tongue within the oral and pharyngeal cavities. If such restrictions affect the production of all vowels, a lower F2 might be assumed for the front vowels, which normally have a high F2; a higher F2 frequency would be anticipated for back vowels, which normally have a low F2. The limited sample studied supports this assumption. PMID- 1608249 TI - Young children's idiom comprehension: trying to get the picture. AB - Young children (3.5-6.5 years of age) were tested for their comprehension of 10 common idioms in context and no-context conditions. Results revealed a significant linear trend for children to make more literal responses with increasing age. Children of this age did not find the story contexts helpful in interpreting the idioms. A range of comprehension scores was found among the individual idioms, but semantic transparency (as judged by adults) was not related to comprehension. Child-internal and methodologic variables influencing idiom comprehension are discussed. PMID- 1608250 TI - Listening and language at 4 years of age: effects of early otitis media. AB - The effect of early otitis media on preschoolers' listening and language abilities was examined in a cohort of prospectively followed children. At 4 years of age, children considered otitis negative and otitis positive during the first year of life were examined using a speech-in-competition task and several standardized measures of language and cognitive function. An adaptive test procedure was used, with sentence materials from the Pediatric Speech Intelligibility Test (PSI) (Jerger & Jerger, 1984). Results indicated that children with positive histories of otitis media during the first year required a more advantageous signal-to-competition ratio to perform at 50% sentence intelligibility than did their otitis-negative peers. There was no interaction between birth status (high-risk or full-term) and adaptive PSI listening task outcome. No differences between the groups were found in either receptive or expressive language abilities or in cognitive abilities. Further, there was no relationship between any language or cognitive measure and the adaptive PSI result. PMID- 1608251 TI - Converging evidence for underlying phonological representation in a child who misarticulates. AB - The liquid, fricative, and affricate sounds in the phonological system of a single misarticulating child were the focus of converging analyses. These analyses included structured measures of perceptual and productive skills, language sampling, and acoustic analysis of seemingly homophonous forms. The results of perceptual and productive tasks indicated that the child's perception of certain sounds was superior to his productions, but for other sounds, productive skill was superior to perceptual performance. This child's errors of production could be attributed to nonadultlike underlying representations. A two lexicon model of underlying representation best accounted for the data. The findings led to inferences about the child's underlying perceptual and articulatory knowledge of fricative, affricate, and liquid sounds. PMID- 1608252 TI - The acquisition of unrounded vowels in English. AB - This study investigated developmental patterns of acquisition of the unrounded American English vowels /i, I, e, e, ae, a/ by following 6 normally developing children from 22 to 30 months of age. The subjects were examined at approximately 22, 26, and 30 months of age. Results showed that, in general, /i/ and /a/ were mastered early and /I/ and /e/ were least accurate throughout the period of the study. Upon inspection of errors, the following three classes of production errors were identified: (a) intertrial production variability, (b) context sensitive substitutions, and (c) context-free systematic substitution patterns, or articulatory processes. A decrease in production variability and in the occurrence of articulatory processes with age generally coincided with a gradual improvement in accuracy of production. However, substitutions of lower vowels for /I/ were persistent, and the pattern was observed even at 30 months of age. Individual variation was also evident in the production accuracy, the substitution patterns, and the manner of articulatory improvement. PMID- 1608253 TI - Vowel duration in mothers' speech to young children. AB - The purpose of this investigation was to determine whether content words are selectively highlighted through increased vowel duration in mothers' speech to young children. Fifteen mother-child dyads served as subjects. All children (ages 1:6-2:4) were female and had a mean length of utterance between 1.00 and 1.40 morphemes. Each mother was asked to read five experimental stories aloud to her child and to an adult. The vowel durations of both content words and function words in these stories were examined. Vowels in content words--but not function words--were significantly longer in child-directed than in adult-directed speech. It is suggested that this characteristic of child-directed speech might heighten young children's attention to content words and contribute to the exclusion of function words during the early stages of English language development. PMID- 1608254 TI - The access and processing of familiar idioms by brain-damaged and normally aging adults. AB - Idiom interpretation tasks are routinely used in the clinical evaluation of adults with brain damage, and idiom processing has received increasing attention in the psycholinguistic literature. Clinical evidence suggests that adults with unilateral right-hemisphere damage (RHD) are insensitive to nonliteral meanings conveyed by idiomatic expressions and other figurative forms. However, this portrayal is derived from their terminal responses to tasks that reflect multiple aspects of mental operations (off-line measures), obscuring the source of poor performance. This study used an on-line word-monitoring task to assess RHD, left hemisphere-damaged, and normally aging adults' implicit knowledge of familiar idiomatic expressions. Brain-damaged subjects performed similarly to normal controls on this task, even though the clinical subjects fared poorly by comparison on an off-line idiom definition measure. These results suggest that adults with unilateral brain damage can activate and retrieve familiar idiomatic forms, and that their idiom-interpretation deficits most likely reflect impairment at some later stage of information processing. Further, error analysis of idiom-definition performance did not support the customary characterization of RHD adults as excessively literal responders. The paper discusses clinical implications of the nature and use of idiom interpretation tasks. PMID- 1608255 TI - Linguistic and cultural diversity: further problems for determining who shall be called language disordered. PMID- 1608256 TI - Modulation detection in subjects with relatively flat hearing losses. AB - Modulation detection thresholds were measured as a function of modulation frequency in 5 normal-hearing subjects and in 8 subjects with relatively flat, slight-to-moderate hearing losses. The carrier was a broadband noise that was sinusoidally amplitude modulated (SAM) in one of two observation intervals. The spectrum level of the carrier ranged from -10 to 50 dB SPL, and, for a given carrier level, modulation frequency varied from 2 to 1024 Hz. The temporal modulation transfer functions (TMTFs) were fitted very well with a simple equation describing a low-pass filter function. The TMTFs from the normal-hearing subjects were relatively independent of carrier level, although the derived time constant tended to increase slightly with decreases in carrier level, from an average value of 2.5 msec at 30 dB SPL to 6.0 msec at -10 dB SPL. In addition, sensitivity to amplitude modulation (AM) decreased by about 4 dB as the pressure spectrum level of the carrier was decreased from 0 to -10 dB SPL. The TMTFs from 7 of the 8 hearing-impaired subjects were similar to those from the normal hearing subjects when the carriers were presented at equal SPLs, except that the derived time constants were slightly larger in the subjects with hearing impairment. When comparisons were made at comparable sensation levels (SLs), however, the TMTFs from the two groups of subjects were quantitatively similar, with the exception that at the lowest SL (20 dB), hearing-impaired subjects typically were more sensitive to AM than normal-hearing subjects, and the derived time constants from their TMTFs were somewhat smaller. These results, taken together with previously published results, suggest that a broad listening bandwidth is important for normal performance on a temporal resolution task. That the time constant from one of the hearing-impaired subjects was significantly longer than normal, regardless of whether the comparisons were made at equal SPL or equal SL, indicates that other factors can also be important. PMID- 1608257 TI - Reliability of two measures of speech recognition in elderly people. AB - The revised Speech Perception in Noise (SPIN) test and the Dichotic Sentence Identification (DSI) test have been used to help evaluate speech-recognition capabilities in elderly people. We evaluated the test-retest reliability of these measures for 17 subjects aged 63-82 years. The DSI and revised SPIN tests were administered at 65, 75, and 85 dB SPL, with a total of three presentations at each level. Reliability was assessed using a repeated-measures analysis of variance and 95% critical differences for each test. Results raise serious questions about the use of these tests for diagnostic determinations or assessment of speech-recognition ability in elderly people. PMID- 1608258 TI - Form equivalence of the Selective Auditory Attention Test administered to 6-year old children. AB - The form equivalence of the Selective Auditory Attention Test (SAAT) was examined. Forty normal-hearing 6-year-old boys and girls were assigned randomly in equal numbers to one of two groups. Each group listened to four lists of words at 70 dB SPL sound field in one of two orders. Equal mean difficulty and significant correlations between lists in quiet and between lists presented with competing speech substantiate the form equivalence of the SAAT. Form equivalence analyzed for individual subjects confirmed conclusions derived from analysis of group data. A learning effect seen as improved mean performance for the second of the two lists presented in competing speech resulted from the repeated measures experimental design of the study and does not undermine the clinical viability of the SAAT. PMID- 1608259 TI - Psychometric evaluation of a Swedish version of the communication strategies scale of the communication profile for the hearing impaired. AB - The Communication Strategies scale of the Communication Profile for the Hearing Impaired (CPHI) was translated into Swedish and used in several studies of people with hearing impairment (Hallberg & Carlsson, in press; Hallberg, Erlandsson, & Carlsson, 1991). In this study the scale was evaluated in terms of descriptive statistics, corrected item-total correlations, principal component analysis, and internal consistency reliability. Agreement with results from American studies is surprisingly good. Normative data based on three samples are presented: a general Swedish hearing-impaired sample with predominantly sensorineural hearing loss (N = 199), a subgroup of 105 younger subjects with noise-induced hearing loss, and a subgroup of 39 older subjects with sensorineural hearing loss due to heredity and/or old age. A significantly more frequent use of maladaptive behaviors (p less than .001) and verbal communication strategies (p less than .01) was reported by older subjects with age-related and/or hereditary hearing loss than by younger subjects with noise-induced hearing loss. The Communication Strategies scale seems to be an adequately reliable and clinically useful instrument for assessing adaptive and maladaptive strategies in hearing-impaired subjects. PMID- 1608260 TI - The effects of input-output configuration in syllabic compression on speech perception. AB - Speech perception was tested through a broad-band syllabic compressor with four different static input-output configurations. All other parameters of the compressor were held constant. The compressor was implemented digitally and incorporated a delay to reduce overshoot. We studied four different input-output configurations, including a linear reference condition. Normal-hearing and hearing-impaired subjects participated in the experiments testing perception of meaningful sentences as well as nonsense CVCs in carrier phrases. The speech materials were presented in quiet and in noise. The results from the CVCs were analyzed quantitatively in terms of scores and qualitatively in terms of phoneme confusions. Differences in speech perception due to the different input-output configurations were small. The input-output configuration with the highest amplification of low amplitude sounds yielded the best results. Detailed analysis of the results included a correlational analysis with a number of auditory functions characterizing the ears tested. The pure-tone audiogram provided parameters of auditory sensitivity: average audiometric loss and audiometric slope. Psychophysical tests provided parameters of temporal resolution and frequency selectivity: the temporal resolution factor, temporal gap detection, and auditory filter shape. The correlational analysis showed that the subjects with better temporal acuity obtained better results. PMID- 1608261 TI - Evaluation of the speech intelligibility rating (SIR) test for hearing aid comparisons. AB - The SIR test was created for use in hearing aid comparisons. The test protocol obtains listener judgments of the intelligibility of connected speech passages. This study was conducted to evaluate the effectiveness of the SIR test in differentiating among hearing aids. Specific research questions were (a) Is the sensitivity of the SIR test sufficient for differentiating among very similar and slightly dissimilar hearing aids? (b) Does the SIR test result in reliable hearing aid rankings? and (c) What are the effects of using shortened connected speech passages? Ten listeners with hearing impairments rated the intelligibility of both full-length and shortened SIR test passages while wearing each of four individually selected hearing aids representing three different frequency/gain prescriptions. Results suggested that the SIR test is capable of differentiating among slightly dissimilar hearing aids and that hearing aid rankings resulting from speech intelligibility ratings were reliable. The decision to use full length or shortened SIR test passages depends on the outcome the user wishes to maximize. Under the conditions used in this study, maximum sensitivity was achieved with ratings from five shortened passages, whereas maximum reliability was obtained with three full-length passages. PMID- 1608262 TI - Consistent within-session measures of tinnitus. AB - Two psychophysical methods, a method of adjustment (MOA) and a forced-choice double-staircase adaptive procedure (FCDS) (Jesteadt, 1980), were used to measure the predominant pitch and loudness of tinnitus for 11 subjects during one test session. The FCDS within-session variability of matches to tinnitus pitch was smaller than for the MOA and comparable to the within-session variability obtained when the FCDS procedure was used to match objective stimuli that approximated the frequency and level of the tinnitus. The within-session variability of matches to tinnitus loudness was nearly identical for the FCDS and the MOA and comparable to the within-session variability obtained when the FCDS procedure was used to match objective stimuli that approximated the frequency and level of the tinnitus. For 3 subjects who participated in 20 sessions, the two psychophysical methods produced correlated measures of tinnitus that tracked each other between sessions. This suggests that tinnitus may be stable within a brief time span but fluctuant in the long run. PMID- 1608263 TI - Orienting attention in audition and between audition and vision: young and elderly subjects. AB - This study examined 30 young and 10 elderly subjects to test whether orienting of attention could be measured in audition. Orienting in a mixed-modal condition in which stimuli were either auditory or visual was also tested. The dependent measure was the reaction time (RT) to lateralized targets when the locations were predicted by antecedent arrow cues that were correct (valid), were incorrect (invalid), or provided no lateralizing information (neutral). A comparison between the two groups among the different conditions showed that elderly subjects had longer RTs than the younger participants, but the pattern of results was similar in both groups. In addition, a similar RT pattern was found for each modal condition: Valid trials elicited the fastest responses and invalid trials the slowest. These findings suggest that the mechanisms involved in orienting attention operate in audition and that individuals may allocate their processing resources among multiple sensory pools. Moreover, effects seen in orienting attention in audition were similar to those found in vision and are interpretable with the same types of models. Orienting attention appears to be relatively resistant to the aging process in the sample of subjects tested in this study. PMID- 1608264 TI - Reported use of communication strategies by SHHH members: client, talker, and situational variables. AB - Two hundred and twelve members of the Self Help for Hard of Hearing People (SHHH) organization completed a survey that evaluated their use of communication strategies. Reported use of strategies was correlated with attitudinal variables and social-interaction indices. On average, subjects agreed most strongly with questionnaire items stating they would ask a talker to repeat a misperceived utterance. They agreed less strongly with items stating they would ask the talker to restructure or elaborate an utterance. Subjects agreed strongly that they would use the communication strategies with familiar talkers, and less strongly that they would use them with unfamiliar talkers. Subjects who appeared less likely to say nothing after misperceiving an utterance were more likely to disagree that they were frustrated with their speechreading skills, and they appeared less likely to avoid social interactions. Subjects who indicated a greater likelihood of using anticipatory strategies, such as reviewing potential vocabulary before an appointment, were on average more likely to avoid social interactions. They also agreed more strongly that poor speechreaders appear less intelligent. PMID- 1608265 TI - The effect of stimulus duration using the Brookler-Grams closed-loop caloric irrigator. AB - Nystagmic responses to traditional 40-sec, 30 degrees C water calorics were recorded and compared to those obtained with the Brookler-Grams closed-loop irrigator using 30 degrees C, 40-, 50-, and 60-sec irrigations. Significant differences were noted between the responses to the water irrigator and the 40- and 50-sec closed-loop irrigations. The 60-sec closed-loop irrigation produced responses that were equivalent to the responses obtained with the water irrigation in slow component velocity, amplitude, frequency, latency, and duration. The 30 degrees C 60-sec closed-loop irrigation is an acceptable stimulus in electronystagmographic caloric testing. PMID- 1608266 TI - Usage and bioassays in Phyllanthus (Euphorbiaceae): a compilation. III. The subgenera Eriococcus, Conami, Gomphidium, Botryanthus, Xylophylla and Phyllanthodendron, and a complete list of the species cited in the three-part series. AB - References to either indigenous uses or the results of controlled assays are numerous for species of Phyllanthus (Euphorbiaceae). These citations have been arranged by subgenus, section, subsection and species and will be published in four papers, including (in Part IV) analysis, discussion and conclusions concerning apparent clustering of some uses or effects within taxa. This paper (Part III) covers the subgenera Eriococcus, Conami, Gomphidium, Botryanthus, Xylophylla and Phyllanthodendron, and also includes a list of the species cited in this three-part series. PMID- 1608267 TI - Traditional phytotherapy in the Peninsula Sorrentina, Campania, southern Italy. AB - A study on the wild and cultivated medicinal plants used in the Peninsula Sorrentina (southern Italy) is reported; 129 plants distributed among 53 different families beloning to Pteridophytes, Gymnosperms and Angiosperms are used in the treatment of various human diseases. The use of some species is reported for the first time in this paper. PMID- 1608268 TI - Solanum chrysotrichum (Schldl.) a plant used in Mexico for the treatment of skin mycosis. AB - An ethnobotanical field study carried out in 200 rural communities determined that the leaves of Solanum chrysotrichum Schldl. are used in Mexican traditional medicine for the treatment of skin mycosis, being particularly recommended to cure Tinae pedis. Clinical trials were performed using a cream containing 5% of a methanolic leaf extract of this plant. Results showed that 45% of the patients were completely cured after 4 weeks of topical treatment. The rest of the cases improved notably in comparison with the control group of patients using the habitual miconazole treatment. The same plant extract inhibited the growth in vitro of the dermatophytes Trychophyton mentagrophytes, T. rubrum and Microsporum gypseum at MICs under 15 mg/ml. PMID- 1608269 TI - Evaluation of the in vitro antimalarial activity of Picralima nitida extracts. AB - Extracts of Picralima nitida seeds, fruit rind, and stem bark have been investigated in vitro for antimalarial activity. The extracts showed remarkable inhibitory activity against drug resistant clones of Plasmodium falciparum at doses of 1.23-32 micrograms/ml. The dichloromethane extract of the fruit rind was the most active of the crude extracts, with IC50 values of 1.61 micrograms/ml for the Indochina (W-2), clone and 2.41 micrograms/ml for the Sierra Leone (D-6), clone. An alkaloid fraction obtained from the methanol extract of the stem bark gave an IC50 value of 2.00 micrograms/ml and 1.23 micrograms/ml in the W-2 and D 6 clones, respectively. The result supports the continued ethnomedical exploration of the plant as a potential antimalarial drug. PMID- 1608270 TI - Further studies on the hepatoprotective effects of Cochlospermum tinctorium rhizomes. AB - The hepatoprotective activity of the rhisome of Cochlospermum tinctorium was investigated using carbon tetrachloride toxicity on mouse and tert-butyl hydroperoxide in vitro induction of lipid peroxidation and hepatocyte lysis. Aqueous, hydro-ethanolic and ethanolic extracts showed significant dose-dependent hepatoprotective actions. The ethanolic extract showed a hepatoprotective activity at lower doses than silymarin. The ethanolic and hydro-ethanolic extracts exhibited remarkable effects against the induction of lipid peroxidation and hepatocyte lysis; the aqueous extract showed comparatively weaker effects. These differences were related to the chemical composition of the extracts. Among the identified constituents of the drug, phenolic and polyphenolic compounds (gallic and ellagic acids, ellagitannins, flavonoids), carotenoids, triterpenes could be related to the biological activity. PMID- 1608271 TI - Screening of Rwandese medicinal plants for anti-trichomonas activity. AB - A series of 30 medicinal plants used in Rwandese traditional medicine has been screened for anti-trichomonas activity against the protozoan Trichomonas vaginalis. Seventeen plants showed anti-trichomonas activity. PMID- 1608272 TI - Commonly used Indian abortifacient plants with special reference to their teratologic effects in rats. AB - A survey programme was organised in Lucknow and Farrukhabad, two towns of Uttar Pradesh, from March 1987 to July 1987. During the survey, the common folk medicine plants used by women were recorded and Ayurvedic and Unani drug encyclopedias were consulted for the antireproductive potential of these plants. Aqueous or 90% ethanol extracts of the plants of interest were studied in rats orally dosed for 10 days after insemination with special reference to effects on foetal development. Leaf extracts of Moringa oleifera and Adhatoda vasica were 100% abortive at doses equivalent to 175 mg/kg of starting dry material. Only the flowers of Acacia arabica and Hibiscus rosa-sinensis appeared to lack teratologic potential at the doses tested. PMID- 1608273 TI - Antimicrobial constituents of Gomphrena martiana and Gomphrena boliviana. AB - The antimicrobial activity of extracts and constituents of Gomphrena martiana and Gomphrena boliviana (Amaranthaceae) were determined in order to identify the compounds responsible for the folk-medicinal use of these plants. Each extract was evaluated against 20 microorganisms, including Gram-positive and Gram negative bacteria, spore-forming Gram-positive bacteria, an acid-fast bacterium, a fungus and two yeasts. Fractionation of each petroleum ether (PE) extract yielded five 5,6,7-trisubstituted flavones that were separately tested showing high activity against M. phlei (minimum inhibitory concentration (MIC) 15, 20 and 75 micrograms/ml) approaching that of commercial bactericides. Other natural and synthetic flavonoids with diverse structures were also tested to define structure activity relationships. Each EtOH extract was subsequently fractionated and monitored by bioassays leading to isorhamnetin 3-O-beta-robinobioside (MIC 50 micrograms/ml) in both instances. This glycoside is reported here for the first time in G. boliviana. PMID- 1608274 TI - Traditional remedies used in the western Pacific for the treatment of ciguatera poisoning. AB - Ciguatera is a specific type of food poisoning associated with the ingestion of tropical fish, which, although normally safe for consumption, may at times contain high amounts of ciguatoxin, as well as other chemically related toxins. Widespread in tropical regions where coral reefs are present, ciguatera fish poisoning constitutes a major hindrance for local fishing industries, local economies and foreign trade. Because no symptomatic treatment has been totally satisfactory, folk remedies remain of great interest. In this paper, a list of plants used in treating ciguatera poisoning in the Western Pacific region is presented, with emphasis on species whose exact utilization (part of plant used, preparation, dosage) has been determined. PMID- 1608275 TI - Survey of medicinal plants used as antimalarials in the Amazon. AB - Plants traditionally employed for the treatment of malaria in certain areas of Brazil, where this disease is prevalent, were surveyed by interviewing natives and migrants in the Amazon Region. Forty-one plants used for malarial treatment and/or for the related symptoms (fever and liver disorders) were collected and identified. Given the potential of Brazil's forests and medicinal plants, research on traditional plant-based remedies in this country may lead to the development of new drugs. PMID- 1608276 TI - [Risk factors for the heterosexual transmission of HIV from man to woman: a Spanish multicenter study]. AB - BACKGROUND: The aims of this study were to estimate the rate of heterosexual transmission of HIV in a population of intravenous drug users (IVDU), as to well as to identify the possible risk factors associated. METHODS: One hundred thirty heterosexual couples were analyzed in which the male was seropositive for the human immunodeficiency virus (HIV) with the only possible risk factor for the companion being the sexual intercourse with the case index. RESULTS: The rate of global transmission estimated was 16% (confidence interval of 95% = 10-22.4%). The risk factors significantly associated to HIV transmission were: case index of over 30 years of age (OR = 3.1), clinical status IV (OR = 4.1), less than 0.8 x 10(8) lymphocytes/I (OR = 7), antecedents of sexually transmitted disease (STD) in the woman (OR = 4), and the practice of anal intercourse (OR = 3.1). In the multivariate analysis only the clinical status of the case index and the STC antecedents of the woman were statistically significant (p less than 0.05). CONCLUSIONS: In this study some of the classical risk factors for the heterosexual transmission of HIV have been confirmed, and the importance of decreasing the prevalence of STD in the IVDU collective in Spain has been corroborated to lower heterosexual transmission and, indirectly the vertical transmission of AIDS. PMID- 1608277 TI - [A multicenter study of drug use during pregnancy in Spain (IV). The drugs used during lactation. The DUP Working Group Spain]. AB - BACKGROUND: Information on the use of drugs during breast feeding is scarce and rather anecdotal. The aim of this study was to gain knowledge on this issue in Spain. METHODS: The Spanish study on drug use in pregnancy recorded information on the use of drugs among 1,371 participating women, who delivered in 20 hospitals of 15 cities. RESULTS: When approached for interview, 157 women (11%) had opted for artificial lactation. Among those women practicing maternal lactation at the time of the interview (n = 921), the total number of drug exposures after delivery was 1,270 (mean = 1.38; SD = 1.55; range 0-10); as many medicines contained more than one drug, the total number of recorded drug exposures was 2,139. The most frequent indications for the use of these drugs were postpartum haemorrhage, pain and anti-infective prophylaxis, and the most consumed drugs were methylergometrine, metamizol, oxytocin, and amoxycillin. CONCLUSIONS: Women practicing maternal lactation frequently receive some drugs for which the information on their passage to maternal milk and on their safety for the newborn is not available. PMID- 1608278 TI - [Implantable devices for central venous access in cancer patients. Our experience in 217 cases]. AB - BACKGROUND: The need of having a venous via available for infusion of chemotherapy treatment along with the difficulty of repeated venous access in oncological patients has lead to the ever more frequent placement of central venous access systems (CVAS) implanted into subcutaneous tissue. METHODS: From February 1985 to December 1990 217 CVAS were implanted in 205 oncological patients. Twenty-six were Port-a-Cath and 191 were Implantofix. RESULTS: The average of complications was 0.08/100 days of implantation with an incidence of catheter thrombosis obstruction of 0.03/100 days and system infection of 0.02/100 days. Currently 81 devices continue functioning with 23 having been withdrawn due to complications and 17 for completion of the treatment to which they had been submitted. Ninety-one patients died during this follow up. CONCLUSIONS: The CVAS are devices which are of easy placement, simple handling, requiring minimum care and few complications. Their efficacy is confirmed by the analysis of the data presented in the present study. PMID- 1608279 TI - [The diet survey: its value in the clinical picture, epidemiology and policy of nutrition]. PMID- 1608280 TI - [Drug regulation in Spain]. PMID- 1608281 TI - [Lipoproteins and atherosclerosis in systemic lupus erythematosus]. PMID- 1608282 TI - [Hyperthyroid myopathy]. PMID- 1608283 TI - [Cholestatic hepatitis secondary to clomethiazole]. PMID- 1608284 TI - [A good abstract is worth more than a thousand words]. PMID- 1608285 TI - [Cutaneous erythema induced by nifedipine]. PMID- 1608286 TI - Effect of U-50,488H on the contractile response of cardiomyopathic hamster ventricular myocytes. AB - We examined the effects of a selective kappa opioid receptor agonist (U-50,488H) on the contractile properties of single ventricular myocytes from 127 day old control (F1B) and cardiomyopathic (BIO 14.6) hamsters. Myocytes in bicarbonate buffered solution with 1.5 mM [Ca2+] were electrically stimulated with field electrodes in the bath. Length changes were monitored via myocyte edge tracking. Twitch amplitude and the velocity of cell shortening were less in the cardiomyopathic hamster myocytes than in age-matched hamsters (P less than or equal to 0.05). There was a concentration-dependent effect of U-50,488H (0.1-20 microM) to decrease twitch amplitude and shortening velocity in both control and cardiomyopathic myocytes (P less than or equal to 0.001). In cells loaded with the Ca2+ indicator indo-1 the negative inotropic action of U-50,488H was associated with a decreased indo-1 fluorescence transient amplitude. There was no difference in the negative inotropic effect of U-50,488H on control and cardiomyopathic cells. Thus, the CM hamster does not demonstrate a different contractile response to U-50,488H. PMID- 1608288 TI - The role of cellular oxidases and catalytic iron in the pathogenesis of ethanol induced liver injury. AB - Free radical generation and catalytic iron have been implicated in the pathogenesis of alcohol-induced liver injury but the source of free radicals is a subject of controversy. The mechanism of ethanol-induced liver injury was investigated in isolated hepatocytes from a rodent model of iron loading in which free radical generation was measured by the determination of alkane production (ethane and pentane). Iron loading (125 mg/kg i.p.) increased hepatic non-heme iron 3-fold, increased the prooxidant activity of cytosolic ultrafiltrates 2-fold and doubled ethanol-induced alkane production. The addition of desferrioxamine (20 microM), a tight chelator of iron, completely abolished alkane production indicating the importance of catalytic iron. The role of cellular oxidases as a source of ethanol induced free radicals was studied through the use of selective inhibitors. In both the presence and absence of iron loading, selective inhibition of xanthine oxidase with oxipurinol(20 microM) diminished ethanol induced alkane production 0-40%, inhibition of aldehyde oxidase with menadione (20 microM) diminished alkane production 36-75%, while the inhibition of aldehyde and xanthine oxidase by feeding tungstate (100 mg/kg/day) virtually abolished alkane production. Addition of acetaldehyde(50 microM) to hepatocytes generated alkanes at rates comparable to those achieved with ethanol indicating the importance of acetaldehyde metabolism in free radical generation. The cellular oxidases (aldehyde and xanthine oxidase) along with catalytic iron play a fundamental role in the pathogenesis of free radical injury due to ethanol. PMID- 1608287 TI - Effects of treatment of normal and hyperprolactinemic rats with cyclosporine in vivo on the release of gonadotropins and prolactin from their pituitaries in vitro. AB - Cyclosporine (CyA) is extremely useful as an immunosuppressant and it is believed that at least some of its actions are due to antagonizing PRL effects. To determine whether the reported ability of CyA to inhibit gonadotropin release can be modified by PRL, we have examined the effects of treatment of normal and hyperprolactinemic rats with CyA in vivo on the release of LH, FSH and PRL from their pituitaries in vitro. Hyperprolactinemia was induced by implantation of capsules containing diethylstilbestrol (DES) and the animals were examined while the capsules were still in place (DES-IN) or after they had been removed (DES OUT). Treatment with CyA significantly reduced plasma LH levels in control DES-IN rats without reducing basal LH release from the pituitaries of these animals in vitro. In the DES-IN rats, CyA exposure in vivo did not modify plasma PRL levels, but reduced PRL release in vitro, and interfered with the inhibitory action of dopamine (DA) on PRL release. The effect of DA on gonadotropin release in vitro was modified by CyA treatment. Administration of CyA failed to antagonize the suppressive effects of hyperprolactinemia on plasma LH and FSH levels or on the basal rates of gonadotropin release by incubated pituitaries. We conclude that CyA can reduce PRL release but does not interfere with the actions of PRL on anterior pituitary function. PMID- 1608289 TI - Iron deprivation decreases ribonucleotide reductase activity and DNA synthesis. AB - The effects of the iron-chelator, desferrioxamine, and monoclonal antibodies against transferrin receptors on DNA synthesis and ribonucleotide reductase activity were examined in human leukemia K562 cells. Treatment of the cells with desferrioxamine resulted in decreases of ribonucleotide reductase activity, DNA synthesis, and cell growth. Exposure of the cells to anti-transferrin receptor antibody, 42/6, which blocks iron supplement into cells caused decreases of ribonucleotide reductase activity and DNA synthesis, in a parallel fashion. Decreases of ribonucleotide reductase activity and DNA synthesis by 42/6 were restored by the addition of ferric nitriloacetate. These results indicate that ribonucleotide reductase activity is dependent on the iron-supply and also regulates cell proliferation. PMID- 1608290 TI - Acquisition of enhanced natural killer cell activity under anesthesia. AB - An increase in natural killer (NK) cell activity can be conditioned with a one trial learning paradigm to demonstrate the interaction between the central nervous system (CNS) and the immune system. In order to demonstrate learning possibilities during 'non-conscious' state, mice were anesthetized with a ketamin/rompun mixture and underwent one trial learning with odor cue as the conditioned stimulus (CS) preceding the unconditioned stimulus (US). The results indicated that mice that were exposed to camphor odor cue under the influence of anesthesia can associate the signal with the poly I:C unconditioned stimulus and were able to recall the conditioned response upon reexposure to the CS. Secondly, the conditioned association made in a conscious state can be recalled by exposure to the same olfactory odor cue in a 'non-conscious' state. The increase in the conditioned change in NK cell activity of both situations was significantly higher than the control group. The results demonstrate that learning can take place and the learned response can be recalled under the reduced awareness caused by anesthesia. The findings we report are unusual and novel in that they demonstrate that the CNS can learn new associations under conditions where the host is apparently unaware of the signals being linked. Anesthesia combined with the long interstimulus interval indicates that certain neuronal pathways in the CNS are receptive to second signals (elicited by the US) even when the second signal is separated by one day. This means the conditioned learning of a physiological response can take place unconsciously at a separate level and under situations where the host is totally unaware of the events which the brain is processing and linking as incoming information. PMID- 1608291 TI - IL-1 alpha increases arachidonyl-CoA: lysophospholipid acyltransferase activity and stimulates [3H]arachidonate incorporation into phospholipids in rat mesangial cells. AB - The proinflammatory cytokine interleukin-1 alpha is a potent stimulus of prostaglandin synthesis. We have previously shown that IL-1 amplifies mesangial cell prostaglandin synthesis by inducing synthesis of a non-pancreatic phospholipase A2. Phospholipase A2 activation results in the formation of lysophospholipids and free fatty acids. We now investigate the effects of IL-1 alpha on reacylation of lysophospholipids. Incubations with IL-1 alpha for 24 hours significantly stimulated mesangial cell [3H]arachidonic acid incorporation but not [3H]oleic acid incorporation into phosphatidylinositol and phosphatidylethanolamine. Lysophospholipid acyltransferase activity was measured in vitro. Cytokine treatment increased enzyme activity when lysophosphatidylcholine, lysophosphatidylethanolamine and lysophosphatidylinositol were used as exogenous substrates. We conclude that IL-1 promotes cellular phospholipid remodeling by stimulating the deacylation and reacylation of phospholipids. PMID- 1608292 TI - alpha N-acetyl human beta-endorphin-(1-31) alleviates the morphine withdrawal syndrome in rodents: a comparative study with clonidine. AB - The potential effect of intracerebroventricular (icv) alpha N-acetyl human beta endorphin-(1-31) on morphine dependence was examined in mice and rats. Animals were rendered tolerant-dependent by subcutaneous (sc) implantation of an oily suspension (10 ml/Kg mouse and 3 ml/Kg rat) containing 0.1 g/ml of morphine. After 72 h of chronic morphine, 1 mg/Kg sc naloxone precipitated in both species a withdrawal syndrome that was moderate in animals pretreated with the acetylated derivative of beta-endorphin. Doses of 28 fmols/rat or 80 fmols/mouse alpha N acetyl human beta-endorphin-(1-31) reduced the number of animals presenting the jumping behaviour, as well as the number of jumps recorded. Moreover, less than half of the rats presented the other withdrawal signs evaluated: squeak on touch, diarrhoea, chattering, chewing, ptosis and body shakes. This activity could be observed when alpha N-acetyl human beta-endorphin was injected 1 h to 24 h before naloxone; longer intervals resulted in a significant loss of this activity. The alpha 2 agonist clonidine given icv at pmol-nmol doses decreased the incidence of morphine withdrawal syndrome. Combinations of these two substances generally did not produce any further enhancement of the effects of clonidine and alpha N acetyl beta-endorphin when used alone. Icv injections of the antagonist of alpha 2-adrenoceptors yohimbine prevented both clonidine and alpha N-acetyl beta endorphin-(1-31) from reducing the jumping behaviour displayed by morphine abstinent mice. It is suggested that alpha N-acetyl beta-endorphin produces this alleviation of the morphine withdrawal syndrome by improving the efficiency of alpha 2-mediated agonist effects after acting on a neural substrate that is distinct from the mu opioid receptor binding site. PMID- 1608293 TI - Mitochondrial and microsomal cholesterol mobilization after oxidative stress induced by adriamycin in rats fed with dietary olive and corn oil. AB - The influence of three different dietary fats (8%) and of endogenous lipid peroxidation with regard to cholesterol concentrations in liver mitochondria and microsomes and in serum has been investigated in the rat. Although the different diet fat used did not produce any effect on serum cholesterol, it was possible to show that each experimental diet differently influenced the microsomal and mitochondrial levels of cholesterol. The highest mitochondrial and microsomal cholesterol content was found in case of diet supplemented with virgin olive oil and the lowest with rectified olive oil. An endogenous oxidative stress induced by adriamycin was able to produce a clear decrease in microsomal and mitochondrial cholesterol level and a sharp increase in serum concentration in all three groups. However, dietary fats and adriamycin had no effect on the microsomal and mitochondrial membrane viscosity as detected by fluorescence polarization. These results are consistent with the hypothesis that mitochondrial and microsomal cholesterol can exchange with exogenous pools when phospholipid peroxidation occurs. PMID- 1608294 TI - Specific G proteins mediate endothelin induced contraction. AB - Endothelin is a potent vasoconstrictor peptide which has recently been localized in the gastrointestinal tract. We have investigated the transmembrane signaling properties of endothelin in isolated smooth muscle cells of the rabbit rectosigmoid. Endothelin induced a dose dependent contraction of smooth muscle cells in a range of 10(-10) to 10(-6)M. In normal buffer, contraction peaked at 30 sec and was sustained for up to 8 min. Incubation in 0Ca/2mM EGTA abolished the sustained contraction induced by endothelin, but had no effect on the initial transient contraction. Preincubation of saponin treated cells with G protein antisera had no effect on control cell length. Preincubation of saponin treated isolated smooth muscle cells with specific G protein antisera (rabbit antisera) for Go alpha or Gs for 60 minutes did not inhibit contraction induced by endothelin. Preincubation with an antiserum to Gi3 alpha inhibited the initial transient contraction induced by endothelin and preincubation with an antiserum to Gi1-2 alpha inhibited the sustained phase of the endothelin induced contraction. Our data indicate that: 1) Endothelin induces a direct sustained contraction of smooth cells from the rectosigmoid; 2) The transmembrane signalling of endothelin is through two specific GTP binding components that are Gi alpha, one for the initial transient contraction, and the other for the sustained phase of the contraction. PMID- 1608295 TI - Fluoxetine-induced inhibition of synaptosomal [3H]5-HT release: possible Ca(2+) channel inhibition. AB - Fluoxetine, a selective 5-HT uptake inhibitor, inhibited 15 mM K(+)-induced [3H]5 HT release from rat spinal cord and cortical synaptosomes at concentrations greater than 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K+ used to depolarize the synaptosomes and the concentration of external Ca2+. Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [3H]5-HT release induced by the Ca(2+) ionophore A 23187 or Ca(2+)-independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K(+)-induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca2+ channels and Ca2+ entry. Whereas fluoxetine and paroxetine inhibited binding of [3H]nitrendipine to the dihydropyridine-sensitive L-type Ca2+ channel, the less selective uptake inhibitors did not alter binding. The dihydropyridine antagonist nimodipine partially blocked fluoxetine-induced inhibition of release. Moreover enhanced K(+)-stimulated release due to the dihydropyridine agonist Bay K 8644 was reversed by fluoxetine. Fluoxetine also inhibited the K(+)-induced increase in intracellular free Ca2+ in fura-2 loaded synaptosomes. These data are consistent with the suggestion that fluoxetine inhibits K(+)-induced [3H]5-HT release by antagonizing voltage-dependent Ca2+ entry into nerve terminals. PMID- 1608296 TI - Compartmental study of rat renal phospholipid metabolism. AB - Phospholipid content and metabolism were studied in rat renal papillary, medullary and cortical slices. The highest concentration of phospholipids was found in cortex and the lowest in papilla samples (ratio cortex/medulla, 1.3; cortex/papilla, 3.7). The profile of the various phospholipids was different depending on the zone. The most important difference was the relative concentrations of sphingomyelin (CerPCho) and phosphatidylinositol (PtdIns) with ratios for PtdIns/CerPCho of 5.0, 3.3 and 2.5 in papilla, medulla, and cortex, respectively. In the three zones, PtdIns showed the highest specific activity for [2-14C]glycerol and [1-14C]arachidonic acid incorporation. By contrast, a higher amount of [1-14C]palmitic acid was incorporated into phosphatidylcholine than into any other phospholipid. The various radioactive precursors were only poorly incorporated into phosphatidylethanolamine. No radioactivity was associated with phosphatidylserine. The papilla possesses the most active phospholipid metabolism of all the pathways studied. PMID- 1608297 TI - Lipids of selected molds grown for production of n-3 and n-6 polyunsaturated fatty acids. AB - The lipid classes and component fatty acids of seven fungi were examined. Three marine fungi, Thraustochytrium aureum, Thraustochytrium roseum and Schizochytrium aggregatum (grown at 30, 25 and 25 degrees C, respectively), produced less than 10% lipid but contained docosahexaenoic acid (DHA) up to 30% and eicosapentaenoic acid (EPA) up to 11% of the total fatty acids. Mortierella alpinapeyron produced 38% oil containing solely n-6 polyunsaturated fatty acids (PUFA) with arachidonic acid (AA) at 11% of the total fatty acids. Conidiobolus nanodes and Entomorphthora exitalis produced 25% oil and contained both n-3 and n-6 PUFA, with AA at 16% and 18%, respectively. Saprolegnia parasitica produced 10% oil and contained AA and EPA, respectively, at 19% and 18%. The triacylglycerol fraction always represented the major component at between 44% and 68% of the total lipid. Each fungus, except T. aureum, had the greatest degree of fatty acid unsaturation in the phospholipid fraction. The triacylglycerol fraction of T. aureum was the most unsaturated with DHA representing 29% (w/w) of all fatty acids present. The presence of the enzyme ATP:citrate lyase correlated with the ability of molds to accumulate more than 10% (w/w) lipid when the fungi were grown in nitrogen limiting media. In those molds that failed to accumulate more than 10% lipid, the enzyme was absent. PMID- 1608298 TI - Linoleoyl-enriched triacylglycerol species increase in maternal liver during late pregnancy in the rat. AB - In view of the previously reported changes in the fatty acid composition of maternal liver triacylglycerols in late pregnancy, changes in the composition of maternal liver triacylglycerol species were assessed in rats fed a semi-purified diet during pregnancy. Between day 18 and day 21 of pregnancy, total maternal liver triacylglycerols increased by 50%. Triacylglycerol species with a total acyl carbon number (C) of 50 or 60 (C50, C60) remained unchanged while C48 and C52-C58 were relatively increased. The individual triacylglycerol species containing one, two or three linoleoyl moieties were incompletely recovered using a polar high temperature gas-liquid chromatography (GLC) column. Nevertheless, at day 21 compared to day 18, the linoleoyl-containing species were relatively increased by 62-463%, while tripalmitin was decreased by 38%. Our data suggest that despite an adequate intake of linoleic acid (25 g/kg in the diet), maternal hepatic triacylglycerol content of linoleic acid decreased during mid-pregnancy but increased significantly toward term possibly in preparation for the transfer of linoleic acid to the neonate during lactation. PMID- 1608299 TI - Alteration in mouse splenic phospholipid fatty acid composition and lymphoid cell populations by dietary fat. AB - The fatty acid composition of diacyl- and alkylacylglycerophosphocholine (PC), phosphatidylinositol (PI), phosphatidylserine (PS), alkenylacyl glycerophosphoethanolamine (aPE), and diacyl- and alkylacyl glycerophosphoethanolamine (dPE) was assessed in isolated splenocytes from C3H/Hen mice fed one of four purified isocaloric diets for six weeks. Diets contained 20% by weight of either a high-linoleate sunflower oil (Hi 18:2), a high-oleate sunflower oil (Hi 18:1), a mixture of 17% menhaden fish oil and 3% high-linoleate sunflower oil (Hi n-3), or a mixture of 17% coconut oil and 3% high-linoleate sunflower oil (Hi SFA). Spleen weight and immune cell yield were significantly higher (P less than 0.05) in mice fed the Hi 18:1 or the Hi n-3 diets compared with those fed the Hi 18:2 and Hi SFA diets. Distinctive patterns of fatty acids were observed for each phospholipid in response to dietary fatty acids. Dietary fat significantly affected (P less than 0.05) total polyunsaturated fatty acids (PUFA) in PC and dPE, total saturated fatty acids (SFA) in PC, total monounsaturated fatty acids (MUFA), and n-3 PUFA in all phospholipid classes examined. In mice fed the Hi n-3 diet, n-3 PUFA were significantly elevated, whereas n-6 PUFA decreased in all of the phospholipids. In these mice, eicosapentaenoic acid (EPA) was the predominant n-3 PUFA in PC and PI, whereas docosahexaenoic acid (DHA) was the major n-3 PUFA in aPE and PS.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608300 TI - Effect of human mammary MX-1 tumor on plasma free fatty acids in fasted and fasted-refed nude mice. AB - We hypothesized that tumor-bearing (TB) nude mice, because they are reported to have no detectable, circulating tumor necrosis factor (TNF)/cachectin, would regulate their plasma free fatty acid (FFA) levels normally when fasted and refed. We compared levels of individual plasma FFA in response to fasting (24 hr) and to refeeding (for 20 hr after fasting) a fat-free, 65% sucrose diet in control, nude mice and in mice bearing 1.3 +/- 0.4 g MX-1 tumors. Total plasma FFA levels were typically high in 24-hr fasted mice [mean concentrations in microM +/- SE (n); controls 515 +/- 63 (6); TB, 625 +/- 63 (6)]. FFA levels were reduced by 65% in each group in response to refeeding. Each major plasma FFA species fell in response to refeeding, except arachidonate, which did not change significantly (fasted vs. fasted-refed concentrations) in either controls or TB mice. In refed mice, the molar FFA ratio of oleate to linoleate rose; however, that of oleate to arachidonate fell markedly. TB nude mice had normal appetites. We conclude that all species of FFA were mobilized from adipose tissue in a normal manner in TB nude mice; therefore, regulation of adipose triacylglycerol fatty acid mobilization (as plasma FFA) by dietary sugar is probably not affected by MX-1 tumor growth in these mice. Our findings are consistent with the hypothesis that nude mice may be unable to secrete TNF/cachectin in response to tumor growth, but they do not establish whether or not endogenous, circulating TNF/cachectin increases FFA mobilization in any TB animal. PMID- 1608301 TI - Comparative uptake of alpha- and gamma-tocopherol by human endothelial cells. AB - The intake of gamma-tocopherol by North Americans is generally higher than that of alpha-tocopherol. However, the levels of alpha-tocopherol in human blood have consistently been shown to be higher than those of gamma-tocopherol suggesting differential cellular retention of the two tocopherol forms. We sought to resolve this question by studying tocopherol metabolism by human endothelial cells in culture. The time- and dose-dependent uptake of gamma-tocopherol by endothelial cells was similar to that of alpha-tocopherol. To determine the comparative uptake between alpha- and gamma-tocopherol, we adopted two approaches in which cells were enriched with either increasing concentrations of an equimolar mixture of alpha- and gamma-tocopherol; or cells were enriched with a fixed concentration of tocopherols in which the alpha to gamma ratio was varied. Our results indicated that there was a preferential uptake of gamma-tocopherol by the cells. When cells were enriched with either alpha- or gamma-tocopherol and the disappearance of individual tocopherols was monitored over time, gamma-tocopherol exhibited a faster rate of disappearance. The faster turnover of gamma-tocopherol can explain the discrepancy between high intake and low retention of gamma tocopherol in man. PMID- 1608302 TI - Glutathione and antioxidants protect microsomes against lipid peroxidation and enzyme inactivation. AB - The study investigated the relationship between lipid peroxidation and enzyme inactivation in rat hepatic microsomes and whether prior inactivation of aldehyde dehydrogenase (ALDH) exacerbated inactivation of other enzymes. In microsomes incubated with 2.5 microM iron as ferric sulfate and 50 microM ascorbate, ALDH, glucose-6-phosphatase (G6Pase) and cytochrome P450 (Cyt-P450) levels decreased rapidly and concurrently with increased levels of thiobarbituric acid-reactive substances. Microsomal glutathione S-transferase and nicotinamide adenine dinucleotide phosphate-cytochrome c reductase were little affected during 1 hr of incubation. Addition of reduced glutathione partially protected and N,N'-diphenyl p-phenylenediamine and butylated hydroxytoluene completely protected microsomes against inactivation of ALDH, G6Pase and Cyt-P450, as well as lipid peroxidation induced by iron and ascorbate. ALDH was more susceptible than G6Pase to inactivation by iron and ascorbate, and was thus an excellent marker for oxidative stress. Inhibition of ALDH by cyanamide injection of rats exacerbated the inactivation of G6Pase in microsomes incubated with 0.1 mM, but not 25 microM 4-hydroxynonenal (4-HN). 4-HN did not stimulate lipid peroxidation. Thus, 4-HN may play a minor role in microsomal enzyme inactivation. In contrast, lipid peroxyl radicals play an important role in microsomal enzyme inactivation, as evidenced by the prevention of both lipid peroxidation and enzyme inactivation by chain-breaking antioxidants. PMID- 1608303 TI - Nitric oxide, an inhibitor of lipid oxidation by lipoxygenase, cyclooxygenase and hemoglobin. AB - The present study demonstrated that nitric oxide, which is an important mammalian metabolite, can inhibit oxidation by lipoxygenase, cyclooxygenase and hemoglobin. The inhibition is manifested as a lag-phase that is reversible. The inhibitory effect of nitric oxide on lipoxygenase and cyclooxygenase seems to derive from i) the capability of .NO to reduce the ferric enzyme to the ferrous form, which is inactive; ii) competition for the iron site available for exogenous ligands; and iii) the radical scavenging ability of the nitroxide radical. Nitric oxide may act as a modulator of the arachidonic acid cascade and in the generation of oxygen-active species. PMID- 1608304 TI - Formation of formaldehyde and malonaldehyde by photooxidation of squalene. AB - Formaldehyde and malonaldehyde were identified upon exposure of squalene to ultraviolet (UV) irradiation at 300 nm. Formaldehyde was derivatized by reaction with cysteamine to form thiazolidine; malonaldehyde was derivatized by reaction with N-methylhydrazine to produce N-methylpyrazole. The derivatives were subsequently analyzed with a gas chromatograph equipped with a fused silica capillary column and a nitrogen/phosphorus detector. The levels of formaldehyde and malonaldehyde produced increased with irradiation time. The amount of formaldehyde produced reached a maximum of 3.40 nmol/mg squalene after 7 hr irradiation; the maximum amount of malonaldehyde generated, 0.92 nmol/mg, was found after 5 hr of irradiation. Prior to this study, formaldehyde had not been reported as a photoproduct of squalene. Acetaldehyde and acetone were also detected in the irradiated squalene, which may be formed via a 6-methyl-5-hepten 2-one intermediate. 6-Methyl-5-hepten-2-one can also undergo breakdown to form malonaldehyde. PMID- 1608305 TI - Acute toxicity of trans-4-hydroxy-2-nonenal in Fisher 344 rats [corrected]. AB - The potential toxicity of trans-4-hydroxy-2-nonenal (HNE), a product formed in vivo during lipid peroxidation, which is also present in foods, was investigated in Fisher 344 rats. Five groups of five male rats each were given by gavage 1000, 300, 100, 30 or 10 mg/kg body weight HNE dissolved in 0.5 mL corn oil. The sixth group, the control, received corn oil alone. Two rats died 6 and 8 hr after being treated with 1000 mg/kg HNE. These two rats showed extensive acute tubular necrosis of the kidney, but had very little liver damage. Diffuse liver cell necrosis was observed in a dose dependent manner in all the rats killed 14 days after treatment, whereas renal change was mild. Interestingly, body weight of the lowest dosage group was significantly higher than that of the control group at termination of the experiment. The results of this study show that HNE has almost the same toxicity as other enals, such as trans-2-heptenal, and that kidney and liver are the main organs affected by toxicity of HNE. Although animals may have efficient defense systems, such as glutathione, to detoxify low to moderate dosages of HNE, at high doses of HNE this defense system is overwhelmed, resulting in serious renal and hepatic damage. PMID- 1608307 TI - The quantitation of long-chain acyl-CoA in mammalian tissue. AB - Intracellular long-chain acyl-CoA esters are key metabolites in lipid metabolism. A rapid procedure was developed for the isolation of long-chain acyl-CoA from mammalian tissues. Acyl-CoA was extracted from the tissue with chloroform/methanol and separated from other lipid-containing metabolites by phase partition with solvents. The content and the molecular species of acyl-CoA were determined by gas-liquid chromatography. In rat liver and hamster heart, the total acyl-CoA content was estimated to be 83 +/- 11 and 61 +/- 9 nmol/g wet weight, respectively. The results obtained are comparable to those reported in previous studies. The relative ease of this procedure would permit the determination of acyl-CoA contents in a large number of samples. PMID- 1608306 TI - Preparation and properties of gem-dichlorocyclopropane derivatives of long-chain fatty esters. AB - Methyl oleate (18:1) and linoleate (18:2) were readily transformed to the corresponding gem-dichlorocyclopropane derivatives in high yield, using triethylbenzylammonium chloride as the phase-transfer catalyst in the presence of aqueous NaOH and CHCl3. Reaction of dichlorocarbene with methyl 12 hydroxystearate furnished methyl 12-chlorostearate (49%) and 12-O-formylstearate (19%). The hydroxy group in methyl ricinoleate was protected (O-tetrahydropyran 2'-yl) prior to dichlorocyclopropanation of the ethylenic bond. Removal of the protecting group allowed the hydroxy group to be converted to a chloride, O acetyl, azido or O-formyl function. Treatment of methyl ricinoleate with thionyl chloride, followed by the reaction with dichlorocarbene gave the corresponding 12 chloro-dichlorocyclopropane derivative. The dichlorocyclopropane derivative of oleic acid was transformed to a C19 allenic fatty acid when treated with t-butyl lithium. However, the remaining dichlorocyclopropane derivatives containing an additional functional group in the alkyl chain, failed to yield the corresponding allenic derivatives. All derivatives were characterized by a combination of spectroscopic and chromatographic techniques, including infrared, 1H nuclear magnetic resonance (NMR), and 13C NMR spectroscopy. PMID- 1608308 TI - Measurement of bile acid synthesis in man by release of 14CO2 from [26 14C]cholesterol: comparison to isotope dilution and assessment of optimum cholesterol specific activity. AB - Bile acid synthesis can be measured as release of 14CO2 from [26-14C]cholesterol divided by cholesterol specific activity, but this method has not been validated in human subjects. We made twelve comparisons of this CO2 method to standard isotope dilution in six normal subjects and found a mean discrepancy of 6%. Linear regression analysis of one value with respect to the other revealed a correlation coefficient of 0.83 (P less than 0.01), a Y-intercept close to zero ( 4.98) and a slope close to 1 (1.06), suggesting good correspondence between the two methods. To assess the potential for error arising from use of serum cholesterol to estimate specific activity of cholesterol used for bile acid synthesis, we compared synthesis measured using serum free cholesterol specific activity to that measured using bile cholesterol specific activity, which is known to be near isotopic equilibrium with the precursor pool used for bile acid synthesis. Synthesis calculated in these two ways differed by less than 10%. The data indicate that the CO2 method using either serum or bile cholesterol specific activity provides a valid estimate of bile acid synthesis in man. PMID- 1608309 TI - Two novel naturally occurring alpha-methoxy acids from the phospholipids of two Caribbean sponges. AB - The novel (5Z)-2-methoxy-5-hexadecenoic acid (1) was identified in the phospholipids of the sponge Tethya crypta while the also novel acid (6Z)-2 methoxy-6-hexadecenoic acid (2) was found in the phospholipids of the Caribbean sponge Spheciospongia cuspidifera. The methoxy-fatty acids were mainly associated with phosphatidylethanolamine. The double bond positions were determined by gas chromatography/mass spectrometry on the corresponding dimethyl-disulfide adducts and the double bond stereochemistry was ascertained by gas chromatography/Fourier transform infrared spectroscopy. The fatty acid composition of the two sponges is reported. PMID- 1608310 TI - Occurrence of wax esters and 1-O-alkyl-2,3-diacylglycerols in goat epididymal sperm plasma membrane. AB - Two unusual lipid classes were detected by thin-layer chromatography in the neutral lipids derived from goat cauda-epididymal sperm plasma membrane. The lipids were identified as wax esters and 1-O-alkyl-2,3-diacylglycerols based on chromatographic properties, identity of their hydrolysis products, and infrared/1H nuclear magnetic resonance spectral evidence. The membrane contained ca. 3 and 5 micrograms/mg protein of wax esters and alkyldiacylglycerols, respectively. The relative proportions of wax esters and alkyldiacylglycerols in the total neutral lipids were 1.5% and 2.4%, respectively. The lipids contained fatty acids with chain lengths of C14 to C22. The major fatty acids of the wax esters were 14:0, 16:0, 16:1 omega 7, 18:0 and 18:1 omega 9. The fatty acids in alkyldiacylglycerol were 16:0, 18:0, 22:5 omega 3 and 22:6 omega 3. Alkyldiacylglycerol was particularly rich in docosahexaenoic acid (22:6 omega 3) representing 30% of the total fatty acids. The alcohols of wax ester were all saturated with C20-C29 carbon chains. The deacylated products derived from alkyldiacylglycerols were identified as hexadecyl, octadecyl and octadec-9'-enyl glycerol ethers. PMID- 1608311 TI - Incorporation of cyclic fatty acid monomers in lipids of rat heart cell cultures. AB - Primary cultures of newborn rat cardiomyocytes were grown in medium supplemented with cyclic fatty acid monomers (CFAM) which had been isolated from heated linseed oil. The cells were harvested, and lipids were extracted and fractionated using silica cartridges and high-performance liquid chromatography. The CFAM structures isolated from cellular lipids were determined and compared to those that had been supplemented to the medium, using gas-liquid chromatography coupled with mass spectrometry (GC/MS). We found that CFAM were incorporated into phospholipids and neutral lipids of cardiomyocytes. Furthermore, CFAM with a cyclopentyl ring structure were more abundant in cardiomyocytes than were the cyclohexyl ring isomers. Our data suggest that CFAM of the 5-carbon and 6-carbon ring series are metabolized differently in newborn rat cardiomyocytes. PMID- 1608312 TI - Dietary arachidonic and linoleic acids: comparative effects on tissue lipids. AB - The effects of preformed dietary arachidonic acid (AA, 20:4n-6) on murine phospholipid fatty acid composition in tissues capable (liver) and incapable (peritoneal exudate cells, PEC) of desaturating and elongating linoleic acid (LA, 18:2n-6) to AA were investigated. The results were compared with those obtained on matched animals on LA diets by either substituting or supplementing dietary LA with AA. Modest amounts of AA ethyl ester (0.5 wt%) included in the diet significantly increased tissue phospholipid AA levels by 39% and 57% in the liver and in PEC, respectively. The changes were further enhanced when dietary LA and AA intakes were equivalent, i.e., 57% and 68% in liver and PEC, respectively. This enrichment was observed in all phospholipid classes analyzed, with the greatest impact on phosphatidylcholine. In addition, the doubling of dietary LA had little effect on tissue phospholipid AA levels. The data suggest that while the level of n-6 PUFA may have an important effect on tissue fatty acid composition, the type of n-6 PUFA in the diet could be of greater significance. PMID- 1608313 TI - Partially endothelium-dependent relaxing effect of ketamine on the canine basilar artery in vitro. AB - The influence of the endothelium on the vasodilator effect of ketamine and its possible mechanism of action on intracellular calcium levels were investigated. We conducted experiments in vitro on canine basilar arteries precontracted with 5 HT and with potassium at high concentrations. Ketamine (10(-6) to 10(-3) M), added cumulatively, relaxed both 5-HT and high-K(+)-induced contraction of basilar arteries (with or without endothelium) in a dose-dependent manner. The ED50s of ketamine for relaxation of 5-HT and high-K(+)-induced contraction for intact endothelium were 3 x 10(-4) M and 6 x 10(-4) M, respectively, and for denuded preparations, 7 x 10(-4) M and 15 x 10(-4) M, respectively. Methylene blue, which blocks the release and/or the effect of endothelium derived relaxing factor, significantly attenuated the relaxation effect of ketamine on the basilar artery. Our results indicate that the endothelium may be responsible for a part of the vasodilator effect of ketamine. We also examined the effect of pretreatment of basilar artery with ketamine (5 x 10(-4) M) on intracellular calcium levels when contraction was induced by 5-HT or by high K+ concentrations. Ketamine significantly inhibited the phase of the contraction induced by high K+. Thus, the vasodilator effect of ketamine may be mediated by inhibition of calcium influx and by the release of EDRF. PMID- 1608314 TI - [Comparison of anesthetic morbidity and mortality before and after the implementation of quality assurance in Tri-Service General Hospital]. AB - The desire to improve anesthetic outcome is a cornerstone in modern anesthesia. There are many means to reach this goal, such as enforcement in personal training, elevation of monitoring standards, constant vigilance and stern quality assurance (QA). The department of Anesthesiology, Tri-Service General Hospital, has adopted the QA program and implemented it since March 1, 1990. Because there were no significant differences in terms of personnel training, monitoring standards and types of anesthesia and surgery before and after the application of QA program, we investigated the effects of QA on anesthetic major morbidity and coma/mortality. We analyzed the anesthetic results obtained in two separate periods respectively spanning from Jan. 1, 1989 to Dec. 31, 1989 and from Mar. 1, 1990 to Feb. 28, 1991. During the first two months of 1990, the department's personnel were trained to be familiar with the QA program. We compared the anesthetic major morbidity and coma/mortality of one year before the implementation of QA with those in a one-year period after its implementation. Before and after enforcement of QA, there were no significant differences (p greater than 0.05) regarding major morbidity and coma/mortality, but the rates of anesthetic complications were lower after the practice of QA program. Since the functions of QA was aimed at alerting the anesthetic personnel to keep constant vigilance over the act of anesthesia, QA in theory could reduce anesthetic accidents and mishaps related jointly to surgery and anesthesia. The reason why QA did not decrease anesthetic major morbidity and coma/mortality in this study may be due to limited number of anesthesia in relatively short period.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608315 TI - [Comparison of body height and vertebral column length in Chinese parturients]. AB - Spinal anesthesia (SA) is frequently used in parturients undergoing Cesarean sections (C/S). The body height (BH) is commonly believed to be one of the factors influencing the spread of SA, especially in patients with extremes of the BH. Recent studies, however, show that the spread of SA is not related to the BH but to the vertebral column length (VL). This study aims to evaluate the relationship between the BH and VL in Chinese parturients. 258 parturients without vertebral column abnormality undergoing C/S were included in this study. The VL (between C7 prominence and sacral hiatus) of each patient was measured in the right decubitus position. They were divided into 3 groups according to their BH (group A less than 152 cm; group B = in the range of 153-161 cm; group C greater than 162 cm). In each group correlation between the BH and VL was made by linear regression analysis. Also determined is whether there is significant difference between each two groups by unpaired Student's t-test. A p values less than 0.05 is considered as statistical significance. The results of the present study showed that although there exists correlation between the BH and VL, the correlation coefficient (r value) is small in each group (0.29, 0.13, and 0.31 in Group A, B, and C respectively; p less than 0.05). There is, also, no significant difference of the VL among the three groups. Therefore we concluded that the BH and VL did not closely correlate and therefore BH might contribute little to the spread of SA in the Chinese parturients, including those with extremes of BH. PMID- 1608316 TI - [Epidural administration of bupivacaine in glycerine solution can prolong analgesia]. AB - Glycerine has long been used with phenol as a drug depot in control of intractable pain. However, through our literature review, glycerine has never been used to prolong the pharmacological effects of a local anesthetic, such as bupivacaine. Our study is an attempt to use the same mechanism to further extend the pharmacologic effects of a popular long lasting anesthetic in a commonly used technique. Fifteen adult patients with cancer pain received 0.125% bupivacaine via a chronically implanted epidural catheter. In a blind study of pain control: Group I, consisting of 8 patients, received 5 ml 0.125% bupivacaine in normal saline; group II, consisting of 7 patients, received the same amount of the same strength anesthetic dissolved in 50% glycerine. The pharmacological effect was assessed by evaluation of intensity and duration of sensory as well as motor blockade. Our preliminary experimental experience revealed that significant prolongation (11.8 +/- 2.3 h vs 7.6 +/- 1.8 h, p less than 0.01) of analgesia was observed with the glycerine solution as compared to the saline solution. There was no motor blockade or other adverse effects or complications. This markedly prolonged analgesic effect is attributed to the slow release of the local anesthetic agent from the glycerine base which functions as a drug depot. Other clinical applications of this novel approach in pain relief are currently under investigation. PMID- 1608317 TI - Evaluation of anesthesia for obstetric and gynecologic intra-abdominal pelvic surgery in a rural hospital. AB - From March 1, 1990 to August 31, 1991, there were four hundred and forty eight female patients undergoing major lower abdominal obstetric and gynecologic operations in our hospital. The most frequently performed operation in our series was Cesarean section (80.8%). Besides, there were operations for ectopic pregnancy, ovarian cyst, fallopian tube problems and abdominal total hysterectomy as well as radical hysterectomy for cervical cancer. Most of the operations were done under spinal anesthesia (91.3%). The rest were performed under epidural anesthesia (2.2%), general anesthesia (4.9%) or a combined anesthetic technique (1.3%). On one occasion, a Cesarean section was done during cardio-pulmonary resuscitation in the emergency room. Another parturient developed cardiac arrest during spinal anesthesia for Cesarean section with successful resuscitation. Otherwise, only minor complications such as post dural puncture headache (6.4%), nausea and vomiting (13.51%) and hypotension (38.2%) were found. All complications responded to conservative therapy that no prolonged hospitalization or unacceptable Apgar score in the newborns was noted. In addition, intra operative blood transfusion was a rare occurrence. Thus, spinal anesthesia is a safe, effective, simple and inexpensive anesthetic method for major obstetric and gynecologic operations particularly in a rural hospital. PMID- 1608318 TI - Comparison of antiemetic effect among ephedrine, droperidol and metoclopramide in pediatric inguinal hernioplasty. AB - Prevention and treatment of postoperative nausea and vomiting with ephedrine, droperidol and metoclopramide have been reported to be effective. To further investigate their efficacy, 100 pediatric patients scheduled to undergo inguinal hernioplasty on ambulatory basis were divided into five groups, namely, group 1: normal saline (iv) control; group 2: ephedrine 0.5 mg/kg, (im); group 3: droperidol 50 micrograms/kg. (iv); group 4: ephedrine 1 mg/kg. (im); group 5: metoclopramide 0.15 mg/kg. (iv). At the end of surgery, each patient received the drug treatment according to the specified group to which he was randomly assigned. The occurrence of postoperative nausea and vomiting was recorded in the recovery room and inquired at home by telephone within 24 h following surgery by a blinded observer. The authors found that there were no significant differences between the control group and ephedrine groups with whichever dose that was used in the prevention of postoperative nausea and vomiting. Droperidol and metoclopramide were effective in dealing with problem in comparison with control group (p less than 0.05). However, metoclopramide was more suitable than droperidol for pediatric outpatient based on duration of somnolence, return of orientation, and time of discharge. PMID- 1608319 TI - [The anesthetic management of Q-T prolonged syndrome]. PMID- 1608320 TI - Pulmonary barotrauma caused by expiratory check valve malfunction of anesthetic machine. PMID- 1608321 TI - [Guide wire knotting in the femoral vein during central venous catheterization]. PMID- 1608322 TI - [Retrospective epidemiological survey on cancer pain: use of physician's records or nursing records?]. PMID- 1608323 TI - The effect of total intravenous propofol on spontaneous respiration during anesthesia for minor surgery. AB - To evaluate adequate anesthetic depth without unacceptable respiratory consequences during total propofol intravascular anesthesia without intubation, the respiratory response was studied in 20 healthy patients (ASA class I or II), aged 20-50, premedicated with fentanyl 2 micrograms/kg. Anesthesia was induced in all patients with propofol 2.5 mg/kg, subsequently maintained by continuous propofol infusion at 12 mg/kg/h. An additional bolus of 20-60 mg propofol was given when anesthesia was considered inadequately. Assisted ventilation with 100% oxygen through a face mask was applied when apnea time was longer than 60 s. The mask was removed when patients regained spontaneous breathing. During induction stage, 7 patients developed apnea which required ventilatory support, although the period of apnea was short. Among them four regained spontaneous breathing within 5 min, and three within 10 min. PaCO2 significantly increased at both 10 min and 20 min after induction as compared with those before induction (p less than 0.05), while the change between 10 min and 20 min after induction was not statistically different. PaO2 showed little change and also it was not statistically significant. During maintenance of anesthesia spontaneous ventilation was stable and adequate. Though mild hypercapnia was noted, no medication was necessary. There was no episode of arterial oxygen desaturation throughout the course of maintenance. All patients could be adequately anesthetized except for six patients who required additional dose for insufficient anesthetic depth. No major adverse reactions occurred during or after induction. We concluded that the respiratory effect of propofol in total intravenous anesthesia could be divided into two stages: the induction stage and the maintenance stage.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608324 TI - Knowledge increment assessed for three methodologies of teaching physiology. AB - A study was conducted on a group of forty-six students of physiology, to compare the knowledge increment following three different teaching methods. The assessment of knowledge increase was done by a pre-test preceding each teaching method, followed by a post-test for each method. The three methods assessed were: (1) a lecture with audio-visual aids; (2) a formal didactic lecture; and (3) a self-study tutorial. The pre-test/post-test method of assessment was found to be valid and reliable. The results indicated a favourable increment for the audio visually aided lecture and for the self-study tutorial. There was no significant increment for the didactic lecture. A questionnaire completed by the students indicated an overall preference for the audio-visually aided method and a lesser preference for the self-study tutorial. The formal didactic lecture found no favour with the students. PMID- 1608325 TI - SCORPIO: a system of medical teaching. AB - Reform in medical education is gaining momentum through the efforts of organizations such as the World Federation for Medical Education. Through the advocacy of such bodies, educational priorities have been redefined to widen the range of educational settings, upgrade evaluation systems and promote the training of teachers as educators. A system of medical teaching has been developed which addresses these issues. It is known by the acronym SCORPIO. The key elements of the system are that it is Structured, Clinical, Objective Referenced, Problem-based, Integrated and Organized. SCORPIO involves delivering a syllabus through a series of lecture-demonstrations at which students, teachers and patients gather at a defined area. Following a short introductory lecture, students rotate in small groups, through a series of teaching stations. These stations are structured to provide students with a problem-based, integrated learning experience. Assessment stations may be included before, during or after the teaching circuit. The teaching system has been formally evaluated over a period of time and now has an established place in the curriculum of this medical school. PMID- 1608326 TI - Preliminary evaluation of a low cost videoconferencing system for teaching in clinical psychiatry. AB - The use of a digitized low cost videoconferencing system (LCVC) for the teaching of clinical medical students on clinical attachment to a psychiatric ward is described. This work was performed as part of the Telemed project which is evaluating the use of the LCVC in a range of tasks in clinical psychiatry. Any move towards greater reliance on communications technology in psychiatry should take account of the requirements of clinical teaching. The case presentation was used as a teaching paradigm in a controlled study comparing teaching face-to-face with teaching mediated via the LCVC. A questionnaire was developed for student evaluation of the case presentation. General user responses to the LCVC are reported. No significant differences were found between the conditions. User responses were favourable, suggesting that remote interactive teaching via the LCVC warrants further investigation. PMID- 1608327 TI - A prospective controlled trial of teaching basic surgical skills with 4th year medical students. AB - Scrubbing, gowning, gloving and aseptic technique are currently the only formal teaching 4th year medical students receive at the beginning of an 8-week surgery rotation. Teaching is often delegated to junior house staff and early bad habits are difficult to unlearn in post-graduate training. A study population of 4th year medical students from three hospitals were examined. At the beginning of an 8-week surgery rotation technical skills were tested with a simulation appendectomy model at the beginning and end of the surgery rotation. On day one, after a pre-test, a teaching intervention was alternated between two hospitals. A control group received only a post-test. The outcome measure was a cumulative score of the students' performance in technical stations in the simulation model. A comparison was made of the mean post-test scores in the teaching, non-teaching and control groups. An analysis of variance of all post-test scores rejected the null hypothesis at the 0.05 level. Duncan's multiple range test demonstrated a significant difference between the teaching and non-teaching group. Feedback from 25 students indicated the teaching model was practical and relevant. A formal teaching intervention of basic technical skills with 4th year medical students improved their performance on a simulated appendectomy model. PMID- 1608328 TI - Twelve tips to encourage better teaching. PMID- 1608329 TI - Teaching consultation skills by videotaping interviews: a study of student opinion. AB - The need to teach undergraduate medical students the skills of conducting a consultation now seems well established. Several authors have also established the efficacy of using constructive feedback on videotapes of each student's interaction with a patient to enhance such skills. To date, however, students' perceptions of this process have not been reported. Here we present the results of such a study, together with a review of the relevant literature. In our study we found that students felt that their skill at analysing and evaluating consultations had been enhanced, but that they would have liked to have more than one of their consultations taped and reviewed. This last suggestion is discussed in the light of the literature reviewed, as are the advantages and disadvantages of using real or surrogate patients for this kind of training. PMID- 1608330 TI - Teaching interviewing skills: the effect of instructors' academic department. AB - This study examines student evaluations of an interviewing and communications skills course taught in small groups by members of psychiatry and family medicine departments. Student course evaluations for two academic years were analyzed by means of t-tests and multiple regression analyses to explore if the group leader's academic department affected the student's learning experience. Students taught by family medicine instructors rated significantly higher three aspects of the course: the usefulness of the role playing session, the credibility and realism of the videotaping session, and the recommendation that the course be continued. This study found the family medicine instructors to be valued teachers of interviewing and communication skills. PMID- 1608331 TI - Evaluating a workshop designed to help medical students improve their skills in communicating about cancer: methodological considerations--and worries. AB - Increasingly, communication skills training is being introduced into medical schools. Evaluations of post-training assessments document its success and add momentum to this movement. In addition, evaluations of student feedback shape course content and teaching methods. Two types of self-selection might bias evaluations and hence, lead to erroneous decisions: (1) students who attend a course may differ from nonattenders; and (2) students who give feedback may differ from those who do not. These two types of bias were examined in the context of a workshop designed to help medical students talk to patients about cancer. Overall, the need for communication skills training was endorsed. However, sex and experiential differences between attenders and non-attenders were identified and if replicated, could confound post-training evaluations. Similarly, differences between students who were more and less willing to provide feedback suggested that decisions based on student evaluations might systematically shape courses to the needs of unrepresentative student groups. Furthermore, qualitative data suggested that students who are least likely to give feedback, are those most likely to have critical or negative comments. Such a bias could mislead evaluators to underestimate the need for change. Rather than cancel each other out, biases associated with attendance and motivation to provide feedback combined. This is serious, because in practice, evaluators are likely to receive data only from those who both attend a given course and provide feedback. The danger is that evaluators may base decisions on information from a doubly self-selected minority of students. PMID- 1608332 TI - Students' ratings of otolaryngology clerkship activities: the role of residents. AB - The present study was conducted with a sample of junior medical students at Jefferson Medical College to investigate the factors that influence students' overall satisfaction with the otolaryngology clerkship. The most important factor related to their overall satisfaction in the clerkship was their experience with residents, followed by experience with attending physicians, quality of rounds, and of lectures. The number of patients the students encountered, and number of rounds and lectures were deemed less important. Based on these findings, the authors of this paper concluded that the residents' role in teaching should be emphasized and students' satisfaction with the otolaryngology clerkship may be enhanced by developing residents' skills in teaching students. PMID- 1608333 TI - The paperless essay: one way to teach writing and computer skills in medical school. AB - We designed an assignment for first-year medical students that included instruction in writing and in computer use, two important subjects that are usually neglected in the traditional curriculum. As part of a neuroscience course, students wrote an essay using a word processor and submitted it to the instructor via the campus computer network. If requested by the instructor, the students submitted a revision of their essays without a grade penalty. As a result of completing the assignment, students learned the importance of revision and were stimulated to learn more about computers. With only slight modification of medical school courses, faculty can place more emphasis on writing skills and computer literacy. PMID- 1608334 TI - Computer based learning in general practice--options and implementation. AB - A survey of the 30 departments of general practice in the UK revealed that only three are currently making use of any form of computer based learning materials for teaching their undergraduate students. One of the reasons for the low level of usage is likely to be the relatively poor availability of suitable courseware and lack of guidance as to how to utilise what is available. This short paper describes the types of courseware that are available and the advantages and disadvantages of using acquired courseware as opposed to writing your own. It also considers alternative strategies for making computer based learning (CBL) courseware available to students. PMID- 1608335 TI - Structural change in fiber matrix allows for enhanced permeability and reduced hydraulic conductivity. AB - Because various diseases, notably diabetes mellitus, are associated with a progressive dissociation within the same organ between hydraulic conductivity (which decreases) and macromolecular permeability (which increases), it was the aim of this study to investigate whether the fiber matrix model for capillary basement membrane and intercellular material can accommodate such clinical findings. Using initial values obtained in this laboratory for a normal fiber radius of .752 nm, a void volume ratio of .627, and a macromolecular test probe radius of 3.6 nm, we found that a wide range of increases in fiber radius and reductions in void volume ratio brought about by fiber dilution are compatible with the clinical observations. PMID- 1608336 TI - Disruption of endothelial actin microfilaments by protein kinase C inhibitors. AB - In this study, we report that the isoquinolinesulfonamide inhibitors of protein kinase C (PKC), H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine] and its related derivatives H-8 and HA-1004, in addition to staurosporine cause depletion and reorganization of microfilament bundles of porcine aortic endothelial cells in both low-density and confluent monolayer cultures. Concomitantly, significant loss of cell adhesion was noted following treatment with H-7. The effects of these compounds were found to be reversible upon wash-out, with restoration of the microfilament network. In addition, longer term incubation with phorbol myristate acetate (PMA) carried out to deplete PKC results in depletion of microfilaments as well. After 24 hr of PMA incubation, however, addition of H-7 or staurosporine is associated with further loss of the remaining microfilaments, suggesting that these agents act, at least in part, through a PKC-independent mechanism. PMID- 1608337 TI - Regional hydrostatic pressure differences: relation to spatial variations in arteriolar cell flux and tone. PMID- 1608338 TI - Organ-derived microvessel endothelial cells exhibit differential responsiveness to thrombin and other growth factors. AB - To investigate the relationship between endothelial cells and organ-associated vascular physiology, microvascular endothelial cells were isolated from murine brain, lung, and liver tissues. During culture, these endothelial cells maintained certain differentiated characteristics common to all endothelial cells, but also showed organ-specific characteristics, with distinct patterns of responsiveness to various growth factors. Microvascular endothelial cells from all organs responded to endothelial cell growth factor (ECGF), but lung (LE-1) and brain (MBE-12) endothelial cells showed different responsiveness to thrombin (10-60 nM), combinations of thrombin and ECGF, or thrombin and extracellular matrix. Liver sinusoidal endothelial cells (HSE) were relatively unresponsive to thrombin, but were the most responsive of the endothelial cells to EGF. Endothelial cells isolated from lung and brain, where fluxes in vascular permeability are observed following injury, showed dramatic morphological alterations in response to nanomolar concentrations of thrombin. These cells also exhibited the highest amount of 125I-thrombin binding at these concentrations. Scatchard analysis of 125I-thrombin binding indicated that LE cells have the highest affinity for thrombin, followed by MBE, with HSE exhibiting significantly lower affinity. The binding of 125I-thrombin to these cells was inhibited by the TR-9 monoclonal antibody directed against fibroblast high-affinity thrombin receptors involved in thrombin-stimulated mitogenesis. The results suggest that the differences in growth stimulation observed between organ-derived endothelial cells in response to thrombin, ECGF, and EGF may relate to differential expression of receptors for these factors. These observations demonstrate yet another aspect of the functional heterogeneity of the microvascular endothelium. PMID- 1608339 TI - Skin capillary metrics and hemodynamics in the hairless mouse. AB - The transparency of the homozygous hairless mouse ear permits detailed study of the intact skin microcirculation without surgical interventions to the skin tissue. It is useful to study many microvascular phenomena and has the potential to provide data to clarify issues related to human skin microcirculation. The aim of this investigation was to quantify the normal capillary geometric and hemodynamic parameters. In each of 36 capillary pairs (10 mice), capillary diameter (D), length (L), and velocity (V) were measured and blood flow (Q) and shear rate (S = 8V/D) were calculated. Loops were chosen such that each branch of the capillary pair had a common arteriolar origin, venule confluence, and thus a common pressure difference across each branch, thereby eliminating the confounding effects of these variables on perfusion differences in each of the branches. Temporal and overall distributions for each parameter were determined and comparisons between paired capillaries made. Overall mean +/- SEM were for D, L, V, Q, and S, respectively, 4.8 +/- 0.2 microns, 161 +/- 5 microns, 192 +/- 5 microns/sec, 3.6 +/- 0.3 pl/sec, and 43 +/- 3 sec-1. Symmetry between paired capillaries was assessed by parameter ratios (smaller/larger); for D, V, Q, and S, respectively, these were 0.85 +/- 0.02, 0.66 +/- 0.03, 0.60 +/- 0.04, and 0.64 +/- 0.04 with corresponding distribution medians of 0.86, 0.72, 0.63, and 0.64. Similar comparisons were made for parameters in smaller/larger diameter capillary pairs yielding for V, Q and S; 1.14 +/- 0.12, 0.82 +/- 0.09, and 1.37 +/- 0.14 with corresponding medians of 0.9, 1.07, and 0.69. These composite results provide baseline data on the naturally occurring animal-to-animal variability, temporal variation, and overall parameter value distributions in the capillary network of this experimental model of skin microcirculation. They thus provide the necessary initial framework for subsequent assessments of pharmacological interventions and the study of various pathological processes on capillary perfusion parameters. PMID- 1608340 TI - Effect of extreme elevations in venous pressure on reflection coefficient in the lung. AB - We determined whether the solvent drag reflection coefficient (sigma f) for total proteins of a canine perfused left lower lung lobe (LLL) preparation decreases at elevated venous pressures (Pv). We found that sigma f (estimated using the hematocrit-protein technique) remained constant at all Pv's (30-95 mm Hg) evaluated. These results were unanticipated, since previous studies reported increases in protein permeability at Pv's within this range. We conducted two additional studies to better understand the basis for these observations. In the first, we evaluated the effect of high Pv (85 mm Hg) on sigma f of a canine perfused forelimb preparation and found sigma f to be reduced. This difference in response suggests that the normal sigma f's observed in the LLL were not due to high Pv per se, but rather that there is some intrinsic difference between the pulmonary and the systemic circulations that accounts for the difference. The second study was designed to determine whether the normal sigma f's observed in the LLL at high Pv's provide meaningful information about pulmonary vascular endothelial permeability. We damaged LLL's with alloxan, oleic acid, or HCl and obtained near normal estimates of sigma f at high Pv. These results indicated that it is not possible to easily distinguish between a normal and a damaged pulmonary vasculature when sigma f is measured at high Pv. We suggest that the normal estimates of sigma f obtained at high Pv in the LLL results from an increased fraction of the transvascular flow occurring through pathways that exclude macromolecules. PMID- 1608341 TI - Peptide-containing innervation of rat femoral lymphatic vessels. AB - The lymphatic vessels conduct lymph fluid, proteins, and potentially antigenic material from the interstitium back to the bloodstream via lymph nodes, where solids are removed by phagocytic cells and recirculating lymphocytes and immunoglobulins are added. Immunostaining for two general neuronal markers, protein gene product 9.5 (PGP 9.5), a cytoplasmic ubiquitin C-terminal hydrolase, and synaptophysin, a calcium-binding four-span integral synaptic vesicle membrane glycoprotein, disclosed an abundant innervation of the large femoral lymphatic vessels in rats. This confirms and extends earlier findings based on nonspecific intravital methylene blue and silver impregnation staining methods. Nerves containing neuropeptide Y, C-flanking peptide of neuropeptide Y, and tyrosine hydroxylase, markers of noradrenergic postganglionic sympathetic fibers, were frequent whereas immunoreactivity to vasoactive intestinal peptide, a neuropeptide present in many cholinergic parasympathetic nerve fibers, was sparse suggesting possible sympathetic and parasympathetic influences. Furthermore, calcitonin gene-related peptide- and substance P-containing fibers were also present in the walls of lymphatic vessels suggesting a possible sensory influence in the coordinated myogenic responses. By comparison to normal light microscopy, confocal microscopy was found useful to trace the perihilar penetration of blood and afferent lymphatic vessels in lymph nodes. PGP 9.5-immunoreactive fibers were found in and around lymph nodes suggesting that there is a neural regulation of lymphoid node function. Because of their distribution, peptide-containing nerves may participate in regulating the capacity of the lymphatic pumping activity, and may possibly exert paracrine effects on lymphocytes. PMID- 1608342 TI - Microvascular flow response to localized application of norepinephrine on capillaries in rat and frog skeletal muscle. AB - Recently, Dietrich (1989, Microvasc. Res. 38, 125-135) demonstrated that a local application of a minute amount of norepinephrine (NE, 5.5 mM, 0.01-88 pmole) on a capillary in rat mesentery can elicit constriction of the feeding arteriole 0.5 1.0 mm away. This constriction can reduce or even stop blood flow in capillaries supplied by the arteriole. The main objective here was to show that the phenomenon of reduced flow occurs not only in the rat mesentery but also in other tissues and species. We chose to study the rat tibialis anterior and frog sartorius muscles. Using the same intravital video-microscopic approach as in the mesentery, strong NE stimuli (3 mM) were applied iontophoretically 48 times to 19 capillaries in 10 rats anesthetized with pentobarbital. They resulted in significant reductions (average: 80%) of the red blood cell velocity (VRBC) in capillaries. The onset of these reductions (i.e., 10% decrease from control) occurred within 3-52 sec (average: 20.9 sec) from the time of NE application. Reductions lasted 6.0 min. The same stimuli were applied 42 times to 15 capillaries in 6 frogs anesthetized with urethane. The average VRBC reduction was 86%. The onset occurred within 30.6 sec while the reduction lasted 6.6 min. Under the same conditions, arteriolar diameters in the sartorius muscle decreased significantly from 28.5 to 22.5 microns (n = 8). We also used local microinjection of small droplets of NE (30 mM) to 13 capillaries in 7 frogs. This resulted in a significant VRBC reduction of 64% with an onset time of 44.2 sec and a reduction duration of 17.2 min. Weak NE stimuli (3 microM) applied iontophoretically to 10 capillaries in 5 frogs resulted in marginal, but significant, VRBC reductions (9%). The present study demonstrates that the phenomenon of reduced flow after local application of NE may be a general phenomenon as it occurs also in skeletal muscle in both rat and frog. Our accompanying paper addresses the hypothesis that the phenomenon reflects communication of a NE-induced signal along the capillary. PMID- 1608343 TI - [Human fungal infections. Part 2: Mycoses of the skin and hair]. PMID- 1608344 TI - [Vitamin B6 in premenstrual syndrome?]. PMID- 1608345 TI - Isosorbide mononitrate for angina. PMID- 1608346 TI - Capsaicin--a topical analgesic. PMID- 1608347 TI - Cefprozil. PMID- 1608348 TI - Cranial computed tomographic findings in children with newly diagnosed acute lymphoblastic leukemia: a prospective follow-up study during treatment. AB - Cranial computed tomography (CT) was performed on 40 consecutive children with newly diagnosed acute lymphoblastic leukemia (ALL) on admission before any chemotherapy, 5 months after CNS therapy (n = 39) and after 2 to 3 years of therapy (n = 31). Changes related to leukemia were found in only 10% of the patients at the time of diagnosis (4/40). These initial changes, two intracranial hemorrhages, one dural thickening and one contrast enhancement, all disappeared during therapy. The findings which persisted unchanged in the next two CT scans were thought to be normal variations or caused by earlier disorders. CNS therapy consisted of intrathecally and intravenously administered methotrexate in 20 standard risk (SR) patients and cranial irradiation in addition to chemotherapy in 19 intermediate risk (IR) or high risk (HR) patients. Four SR patients developed changes during therapy. Three had enlarged cerebrospinal fluid (CSF) spaces and one developed a focal low density area suggesting disturbances in brain blood circulation and also experienced disturbances in level of consciousness. Of the 19 IR or HR patients, eight developed changes related to the therapy, including four with white matter hypodensity areas, of whom three also had enlarged CSF spaces, and four others who developed enlarged CSF spaces. The medians of the widths of the cortical sulci (P less than .001), insular cisterns (P less than .01), third ventricles (P less than .01), and frontal horns (P less than .05), and also of Evans' ratios (P less than .05) increased significantly after CNS therapy as compared with the findings at diagnosis in the patients who had received cranial irradiation. Most of these changes persisted during the follow-up. We conclude that the clinical value of CT scanning during therapy for ALL is restricted to patients with neurological symptoms or those who have undergone CNS irradiation. PMID- 1608349 TI - Lymphoma in Sjogren's syndrome. AB - Sjogren's syndrome is an autoimmune disease with a known predisposition for lymphoma development. Eight of 120 patients with primary Sjogren's syndrome followed at the University of Ioannina over the past 7 years developed non Hodgkin's lymphoma diagnosed according to the Kiel classification. The lymphomas differed by location and grading. Six were called low grade (immunocytoma) and two intermediate grade non-Hodgkin's lymphomas. Five of the immunocytomas involved the minor salivary or lacrimal glands. Immunoperoxidase staining for light chains revealed monoclonal populations. Two patients showed spontaneous regression not previously reported in Sjogren's syndrome. Thus, in Sjogren's syndrome, low grade non-Hodgkin's lymphomas and especially immunocytomas are the most common lymphomas. These lymphomas tend to evolve very slowly and may regress spontaneously. Given these facts, a conservative approach to treatment is indicated in those patients with only localized disease. PMID- 1608350 TI - N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis. AB - N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma. PMID- 1608351 TI - Smoking habits in survivors of childhood and adolescent cancer. AB - Because of their increased risk for second cancers, childhood cancer survivors are people who really should not smoke, but available evidence suggests that they do. We studied the smoking habits of long-term childhood cancer survivors in data collected from 1289 adult survivors of childhood cancer and 1930 of their sibling controls. Survivors were diagnosed with cancer between 1945 and 1974 when they were less than 20 years old. Using matched analyses that controlled for the influence of family, survivors were 8% less likely than controls to be current smokers, 13% less likely to be ever-smokers, but 12% less likely to have quit smoking; these differences were not statistically significant. In a logistic regression analysis there was a significant difference by year of diagnosis for current smoking rate ratios (RR); survivors were less likely to be current smokers if diagnosed in recent years (RR = 0.76; 95% confidence intervals = 0.58 0.98, between 1965-74) and quite similar to controls if diagnosed in earlier years (RR = 1.05 between 1945 and 1954). In our group of long-term cancer survivors, the reduction in current smoking came about because survivors were more inclined never to start smoking than controls. Once addicted to tobacco, they were less likely to quit. While the fact that survivors are less likely to start smoking is encouraging, the persistence of smoking habits strongly suggests the need for continuing efforts to prevent smoking in this most vulnerable group. PMID- 1608352 TI - 13-cis-retinoic acid (NSC 122758) in the treatment of children with metastatic neuroblastoma unresponsive to conventional chemotherapy: report from the Childrens Cancer Study Group. AB - The Childrens Cancer Study Group evaluated daily oral 13-cis-retinoic acid to determine its therapeutic efficacy in 28 children with advanced neuroblastoma refractory to conventional therapy. Cheilitis and fissured lips were the most common side effects; however, fewer than 50% of the patients experienced any toxicity. Two of twenty-two evaluable children demonstrated positive response to therapy. In one case, a child received the drug for 11 months. Seventeen patients demonstrated progressive disease within 28 days of the start of treatment. Three other patients with stable disease, or removed from study at day 28, were considered nonresponsive. Our data demonstrate that, when given as a single daily oral dose of 100 mg/m2, 13-cis-retinoic acid does not have significant activity in children with advanced neuroblastoma. PMID- 1608354 TI - Continuous-infusion 5-fluorouracil combined with doxorubicin and cyclophosphamide: feasibility study. AB - Previous studies have demonstrated continuous-infusion 5-fluorouracil (CI 5-FU) to be an active single-agent treatment for breast cancer without significant myelotoxicity. These qualities made CI 5-FU an attractive agent for combination with other effective but myelosuppressive agents. In this study we attempted to determine the maximal doses of CI 5-FU that could be added to a combination of agents known to be dose limited by myelotoxicity, doxorubicin 50 mg/m2 day 2 and cyclophosphamide 150 mg/m2 days 3-12 of a 28-day cycle. Patients who received doxorubicin and cyclophosphamide alone developed significant myelotoxicity but did not develop stomatitis. The addition of 5-7 days of CI 5-FU at 200-300 mg/m2 was associated more closely with increased stomatitis (P = .11) than with increased granulocytopenia (P = .57). The stomatitis observed for low doses of CI 5-FU given with doxorubicin and cyclophosphamide would not have been expected for these low doses of CI 5-FU given as a single agent. We conclude that the addition of CI 5-FU to myelotoxic doses of doxorubicin and cyclophosphamide is not a promising therapeutic strategy for significantly increasing the effectiveness of this combination of agents. PMID- 1608353 TI - Treatment of malignant scala posterior brain tumors in children: the chemotherapy of relapsed medulloblastoma with a dibromdulcitol containing drug regime and pharmacokinetic studies of dibromdulcitol in children. AB - Dibromdulcitol (Elobromol) has favorable pharmacokinetic parameters for the treatment of brain tumors: high spinal fluid/plasma ratio and long half-life in spinal fluid. Oral application makes its administration easy. The drug combination vincristine, procarbazine, and dibromdulcitol proved to be effective in a pilot trial on relapsed medulloblastomas: 8 complete and 4 partial remissions were achieved from 16 cases. The main side effect was granulocytopenia, which was in some cases severe. However, in the dose-schedule we used it did not delay the treatment longer than 1 week. PMID- 1608356 TI - "Shuttle sheet": a patient-held medical record for pediatric oncology families. AB - A patient-held medical record used by a pediatric oncology unit is described. Each patient's family is provided with a folder containing detailed information about the patient's current treatment. The record helps orient all health care workers involved in the patient's management to the treatment schedule, including exact doses of drugs. Details of blood counts and treatment given are entered by health care workers at each consultation, but the record is always retained by the family. The benefits of this record are that it saves time, reduces the likelihood of errors in scheduling and doses of cytotoxic drugs, and facilitates continuation of therapy at locations away from the supervising oncology unit. It reduces the amount of correspondence required for patient care, is a useful diary and treatment planner for the patient's family and hospital staff, and is an educational resource for the patient's family. It is a useful adjunct to the hospital's medical record for clinical trial data, is easily replaced if lost, and is inexpensive. It also assists surveillance of long-term survivors. The record is particularly valuable when used with patients who are being treated or assessed at more than one institution or by multiple health care workers. The record is in its 12th year of service and is used by more than 95% of patients on therapy attending the unit. PMID- 1608355 TI - Phase II trial of ifosfamide/mesna and mitoxantrone in previously treated patients with non-Hodgkin's lymphoma: cancer and leukemia group B study 8753. AB - Ifosfamide (2.0 g/m2 intravenously/day x 3) with mesna (400 mg/m2 intravenously q 4 h daily x 3) was combined with mitoxantrone (14 mg/m2 intravenously x 1) and given on a 3 week schedule to patients with previously treated non-Hodgkin's lymphoma. In 45 eligible/evaluable patients, a 47% response rate (95% confidence interval: 32%, 62%) was achieved of which 25% were complete responses and 22% were partial responses. Median duration of remission was 10 months with 42% of patients in remission at 18 months. Hematologic toxicity (granulocytopenia) was the dose-limiting toxicity with severe or life-threatening granulocytopenia in 98% of patients at full protocol doses. Nausea/vomiting was seen in 73% of patients but was usually mild/moderate. Three patients had significant hematuria secondary to ifosfamide. Two patients had severe changes in the left ventricular ejection fraction (LVEF) secondary to mitoxantrone; and one patient had acute neurologic dysfunction secondary to ifosfamide. Ifosfamide/mesna can be safely combined with mitoxantrone at full doses in previously treated patients with non Hodgkin's lymphoma. This combination should be considered for other trials in lymphoma. PMID- 1608357 TI - Interferon and disseminated Langerhans cell histiocytosis. PMID- 1608358 TI - Management of testicular seminoma following organ transplantation. AB - An increased incidence of malignancies has occurred in recipients of organ transplantation who are immunosuppressed. Although testicular cancers have been uncommon, seminomas are extremely rare. Two patients with long-standing diabetes mellitus and renal transplants developed clinical stage I seminoma of the testis. These patients posed a therapeutic problem with respect to the use of radiation therapy. In one, none was given because of a combination of kidney rejection and antibiotic-induced renal damage. The second patient received radiation therapy with shielding of the transplanted kidney. The surgical distortion of lymph node architecture increases the problems in the use of radiation therapy. Individual factors need to be considered in the use of postorchiectomy radiation therapy for seminoma in transplant patients. PMID- 1608359 TI - Secretory breast cancer in childhood and adolescence: report of a case and review of the literature. AB - A 17-year-old boy underwent a wide partial mastectomy with axillary dissection for secretory breast cancer, followed by low grade irradiation (30 Gy). There were no axillary lymph node metastases. Hormone receptor assay of the tumor was positive for progesterone and negative for estrogen. There was no local recurrence or sign of dissemination after nearly 5 years. Literature search revealed 21 cases of secretory breast cancer in childhood and adolescence; in only 2 cases was the hormonal status studied. We report an additional case and review the literature. PMID- 1608360 TI - Cutaneous angiosarcoma as a second malignant neoplasm after peripheral primitive neuroectodermal tumor. AB - Second malignant neoplasms (SMN) in late childhood or young adulthood in individuals who have been successfully treated for an initial malignancy have emerged as a late effect of therapy in survivors of childhood cancer. Although radiation therapy is frequently implicated, chemotherapy with alkylating agents and antimetabolites has also been associated with SMN. Soft tissue sarcomas are among the most frequent primary malignancies complicated by a SMN and account for a majority of nonhematolymphoid SMN. We present the clinical and pathologic findings in a patient who had a peripheral neuroepithelioma (primitive neuroectodermal tumor, PNET) of the soft tissues diagnosed at 17 years of age, was treated with high-dose irradiation and multidrug chemotherapy, and developed an angiosarcoma 14 years later. This case represents an uncommon combination of mesenchymal malignancies in a young patient with an unusually favorable clinical course following the diagnosis of PNET. PMID- 1608361 TI - Chemotherapy for pancreaticoblastoma. PMID- 1608362 TI - Desmoplastic soft tissue tumor. PMID- 1608364 TI - Changes in brain regional manganese and magnesium levels during postnatal development: modulations by chronic manganese administration. AB - Manganese (Mn) and magnesium (Mg) levels in hypothalamus, cerebellum, pons and medulla, striatum, midbrain, and cerebral cortex of control and Mn-treated (10 mg MnCl2.4H2O per ml of drinking water) rats during postnatal development were studied using instrumental neutron activation analysis. The age-dependent Mn accumulation showed regional variation: at day 5, this accumulation was most marked in striatum (12.05 micrograms/g wet weight) but least marked in cerebral cortex (0.85 micrograms/g wet weight). By day 10, pons and medulla, and hypothalamus were regions with, respectively, the highest (4.73 micrograms/g wet weight) and the lowest (0.52 micrograms/g wet weight) Mn levels. By contrast, brain regional Mn variations were less pronounced in weanling and adult rats. The age-dependent Mg accumulation showed regional variation at day 5, being most marked in pons and medulla (720 micrograms/g wet weight) and least marked in cerebral cortex (295 micrograms/g wet weight). Mg levels in all regions decreased after day 5; by day 120, only Mg level in cerebral cortex was lower than levels in other regions (the latter being very similar). In general, the age-related decreases in Mn and Mg levels paralleled the decreases in water content and increases in tissue weight, suggesting that the maturation of the blood-brain barrier may play important role(s) in brain Mn and Mg homeostasis. Chronic Mn treatment from conception onwards altered the regional Mn and Mg distribution patterns during development. Our results are consistent with the hypothesis that chronic Mn toxicity exerts modulatory effects on brain regional metabolism and homeostasis of Mn and other metals during development. PMID- 1608365 TI - Protection against hippocampal CA1 cell loss by post-ischemic hypothermia is dependent on delay of initiation and duration. AB - The temporal constraints of protection of neuronal damage by post-ischemic hypothermia was investigated in the gerbil model of global ischemia. Three experimental paradigms were used: 1) Hypothermia was initiated prior to ischemia followed by warming to normothermia immediately post ischemia; 2) Hypothermia of different durations was initiated immediately after reflow and 3) Six hours of hypothermia was initiated at various times following reperfusion. Hypothermia during 5 minutes of ischemia followed by warming to normal body temperature immediately post ischemia resulted in near complete protection of the hippocampus from CA1 cell loss. Hypothermic durations of 1/2, 1, 2, 4, and 6 hours beginning immediately following reperfusion resulted in progressively increased protection from ischemic damage (6 +/- 6%, 21 +/- 10%, 34 +/- 15%, 75 +/- 16% and 77 +/- 12%, respectively). Six hours of hypothermia delayed for 1 hour after reperfusion resulted in 49 +/- 9% protection. No reduction of ischemic damage was observed if 6 hours of hypothermia was delayed for 3 hour after reflow. These data suggest that: 1) Hypothermia during ischemia protects the brain from damage; 2) Hypothermia initiated immediately following reperfusion must have a duration of 2 hours or more to be effective and 3) Six hours of hypothermia is effective if initiated within 1 hour of reperfusion. PMID- 1608366 TI - Surfactant replacement: an old idea breathes new life into neonatalogy. PMID- 1608363 TI - Glutamatergic synaptic dysfunction in hyperammonemic syndromes. PMID- 1608367 TI - Surfactant replacement therapy: issues related to currently available preparations. PMID- 1608368 TI - Impact of surfactant replacement therapy on the nursery. PMID- 1608369 TI - Continuous arteriovenous hemofiltration: an alternative dialysis therapy in neonates. AB - Modifications have made it possible to perform CAVH in the neonate. One of these is decreasing the extravascular volume in the tubing and filter to a minimal amount to allow for adequate intravascular blood volume in the infant. Another is utilizing predilutional fluid to decrease the need for heparinization. A third modification is utilizing the suction-assist pumps to help control the amount of fluid removed from the infant. With modifications of this system to fit the special needs of neonates and intensive nursing and medical management, CAVH can be a successful alternative to traditional dialysis therapies in neonates. PMID- 1608370 TI - Ethical considerations of aggressive care of very low birth weight infants. AB - The issues surrounding aggressive treatment of at-risk infants have tended to be reduced to superficial dichotomies such as parent versus infant rights and sanctity versus quality of life. Public debate has typically been restricted to isolated aspects of extreme individual cases. By routinizing decisions and minimizing use of research protocols in the care of VLBW infants, health care professionals have made issues related to aggressive care appear less consequential than they are. This process, combined with limited access by significant sectors of society, has severely curtailed effective debate about a highly complex and important problem. Nurses have a responsibility to help establish an arena for this debate--in both individual cases and the formulation of public policy--and to facilitate participation by those whose input has been restricted. PMID- 1608371 TI - Attitudinal and resource changes after a neonatal resuscitation training program. PMID- 1608372 TI - Evolution of vaccine development. National Institutes of Allergy and Infectious Diseases. PMID- 1608373 TI - Research and clinical practice. PMID- 1608374 TI - Research and clinical practice. PMID- 1608375 TI - Building a research team. PMID- 1608377 TI - Research and clinical practice. PMID- 1608376 TI - Implementing a professional practice model in the intensive care nursery. PMID- 1608378 TI - Research and clinical practice. PMID- 1608379 TI - Research and clinical practice. PMID- 1608380 TI - Consent: where research design meets reality. PMID- 1608382 TI - Varying instructional methods for staff updates. PMID- 1608381 TI - Periventricular leukomalacia. AB - Serial ultrasound examinations in the preterm infant have documented a strong predictive relationship between PVL and adverse neurologic sequelae, particularly cerebral palsy. Good obstetric management with carefully timed intervention as well as prevention of hypoxic-ischemic episodes postnatally may prevent PVL. The nurse plays a significant role in preventing PVL in the preterm infant. She should understand the risk factors associated with PVL and establish protocols in nursing care to promote minimal handling. Prevention of hypoxemia and wide fluctuations in blood pressure are critical. Careful attention to adequate ventilation and the continuous monitoring of oxygen saturation will help avoid and treat hypoxemia episodes. PMID- 1608384 TI - Concern and increasing criticism of the expanding bureaucracy of the State Board of Registration for the Healing Arts. PMID- 1608383 TI - Naloxone. PMID- 1608385 TI - Tuberculosis control and elimination activities. PMID- 1608387 TI - The role of antibiotics in the management of acute exacerbation of chronic bronchitis (answers to some commonly asked questions). AB - More than 7 million Americans suffer from chronic bronchitis, and it has been estimated that each of these patients will experience between one and four acute exacerbations a year. This problem constitutes a major social and financial burden on our society. Despite the prevalence of this disorder there is still considerable disagreement among physicians as to appropriate treatment, especially with regard to the use of antibiotics. Though the role of antibiotics is unclear, the pharmaceutical industry is trying to obtain regulatory approval of several new antibiotics for use in exacerbations of chronic bronchitis. We examine the role of antibiotics in the management of chronic bronchitis. PMID- 1608386 TI - The use of rectal temperature to monitor heat stroke. AB - The diagnosis and treatment of heat stroke has relied on rectal temperature monitoring. A twenty-year retrospective review of heat stroke and heat exhaustion victims reveals a 24% mortality and a 33% incidence of overcooling. An experimental protocol using hot and cool baths demonstrates marked rectal temperature lag during periods of rapid body heating and cooling. Auditory canal temperature measurements provide an attractive alternative to rectal temperature measurement during rapid temperature change. Rectal temperature monitoring of heat stroke victims is not recommended. This work suggests that shivering during treatment of heat stroke might be the result of vascular and brain overcooling with elevated rectal temperatures. PMID- 1608388 TI - Intranasal melanoma. AB - Malignant melanoma is most commonly associated with cutaneous malignancies of sun exposed skin, but melanoma also occurs in the mucosal surfaces of the head and neck. The symptoms of intranasal melanoma are most often associated with benign conditions that patients often ignore during the early course of the disease. Benign symptoms that persist require thorough evaluation to exclude neoplastic disease in which timely diagnosis and early treatment offers the best prognosis. PMID- 1608389 TI - Malignant tumor of the colon metastatic to the epididymis as a first sign of recurrence of colon cancer. AB - Metastatic tumors to the epididymis are rare. Most reported cases represent another occurrence of widespread disease. This is a report and review of the literature of a case of adenocarcinoma of the colon three years post resection in which the only site of recurrence was in the epididymis. PMID- 1608390 TI - Primary amebic meningoencephalitis--North Carolina, 1991. AB - During September 1991, two children in North Carolina died from primary amebic meningoencephalitis (PAM), a rare and often fatal illness resulting from infection with Naegleria fowleri. This report summarizes clinical and epidemiologic information about these two cases and characterizes N. fowleri infection. PMID- 1608391 TI - Shigellosis in child day care centers--Lexington-Fayette County, Kentucky, 1991. AB - In January 1991, the Lexington-Fayette County (Kentucky) Health Department (LFCHD) received three reports of Shigella sonnei infections from the University of Kentucky microbiology laboratory. The infections occurred in children aged 2-3 years, each of whom attended a different child day care center in Lexington Fayette County (population: 200,000). This report summarizes the findings of an investigation by the LFCHD and the Kentucky Department for Health Services to assess the impact of day care center attendance on communitywide shigellosis. PMID- 1608392 TI - Unintentional firearm-related fatalities among children and teenagers--United States, 1982-1988. AB - In 1988, gunshot wounds were the eighth leading cause of unintentional injury deaths among persons in all age groups in the United States and the third leading cause of such deaths among children and teenagers aged 10-19 years (1). From 1982 through 1988, 3607 children and teenagers aged 0-19 years died from unintentional firearm-related injuries, constituting 32% of all unintentional firearm-related deaths. Of those, 81% occurred among 10-19-year-olds. This article describes a case report of an unintentional firearm-related death of a teenager and summarizes an analysis of demographic and regional differences in unintentional firearm-related mortality among children and teenagers from 1982 through 1988. PMID- 1608393 TI - Fireworks-related injuries--Marion County, Indiana, 1986-1991. AB - Based on data from the Consumer Product Safety Commission's (CPSC) National Electronic Injury Surveillance System, fireworks-related injuries accounted for an estimated 12,400 emergency room visits during 1990 in the United States (1); two thirds of fireworks-related injuries occur during the 4-week period surrounding Independence Day. Since 1986, to better characterize fireworks related injuries and to improve local health education and prevention efforts, the Marion County (Indiana) Health Department (MCHD) has conducted surveillance of fireworks-related injuries. This report summarizes surveillance results for 1986-1991. PMID- 1608394 TI - Public health focus: mammography. AB - Among U.S. women, breast cancer is the most commonly diagnosed cancer and the second leading cause of death from cancer. From 1980 through 1987, the incidence of breast cancer increased from 94.6 to 124.3 per 100,000 women (age-adjusted to the 1990 U.S. population) (1). In contrast, death rates remained stable; during 1988, 31.1 per 100,000 U.S. women died from the disease (Table 1) (2,3). Although the prognosis for breast cancer is more favorable than for many other types of cancers, breast cancer continues to be an important source of years of potential life lost before age 65 (YPLL) (Table 1). White women account for 82% of all YPLL from breast cancer; however, the estimated rate of YPLL during 1988 was approximately 25% higher for black women than white women. For breast cancer, certain primary risk factors (e.g., family history, age at menarche, and age at menopause) cannot be altered and others (e.g., parity and age at first pregnancy) are not practical targets for intervention. Therefore, as a secondary method for prevention of breast cancer, mammography screening is the most commonly recommended intervention. During 1990, 58% of U.S. women aged greater than or equal to 40 years reported having had a screening mammogram within the preceding 2 years (Figure 1). This report summarizes information regarding the efficacy, effectiveness, and cost-effectiveness of mammography screening. PMID- 1608395 TI - Human rabies--California, 1992. AB - On May 8, 1992, an 11-year-old boy died of rabies encephalitis in Fresno County, California. This was the 10th case of human rabies in the United States since 1980 known to be acquired outside the country and the first case reported in California since 1987. This report summarizes the investigation of the case. PMID- 1608396 TI - Update: acquired immunodeficiency syndrome--United States, 1991. AB - During 1991, state and territorial health departments reported 45,506 cases (17.9 per 100,000 population) of acquired immunodeficiency syndrome (AIDS) to CDC. As in previous years, most cases (52.7%) were attributable to human immunodeficiency virus (HIV) transmission among homosexual/bisexual men. The proportion of cases among these men during 1991 decreased from that in 1990, while the proportions among women and heterosexual men who were injecting-drug users (IDUs) increased, representing nearly one fourth of reported cases in 1991. This report summarizes the characteristics of persons reported with AIDS in 1991 and compares these data with 1990 (Table 1).* PMID- 1608397 TI - Cerebrovascular disease mortality and Medicare hospitalization--United States, 1980-1990. AB - Cerebrovascular disease, the third leading cause of death in the United States, disproportionately affects older adults. In 1988, 87% of all deaths from and 74% of all hospitalizations for cerebrovascular disease occurred among persons aged greater than or equal to 65 years. This report presents temporal trends and geographic patterns in mortality and Medicare hospitalizations resulting from cerebrovascular disease among persons aged greater than or equal to 65 years. PMID- 1608398 TI - Chromosomal proteins of Physarum polycephalum with preferential affinity for the sequence, poly d(A-T).poly d(A-T). AB - We have identified two novel chromosomal proteins from Physarum polycephalum using a protein blotting DNA-binding assay. A fraction of these proteins was readily released from nuclei by solutions of moderate ionic strength (0.15 N-0.35 M NaCl) or mild nuclease treatment and appear associated with chromatin that is nucleosome-free. A significant proportion of these proteins, however, was not released from nuclei by solutions of high ionic strength (1.6 M NaCl) or treatment with excess nuclease. These results suggest that these chromosomal proteins are distributed between transcriptionally-competent and inert domains of chromatin. Both proteins preferentially and tenaciously bound duplex DNA, especially to the alternating B-DNA conformation displayed by the synthetic sequence, poly d(A-T).poly d(A-T). PMID- 1608399 TI - Generation of stable human autoantibody-secreting B cell hybridomas. PMID- 1608400 TI - The effect of tunicamycin on the protease activity of GP63 from Leishmania major. AB - The protease activity of gp63 from L. major was studied in relation to tunicamycin induced N-deglycosylation. It was found that after tunicamycin treatment, a N-deglycosylated product of gp63 with protease activity is present at the cell surface of Leishmania promastigote. PMID- 1608401 TI - Effect of genetic background on the developmental expression of c-fos and c-myc in chicken. AB - The developmental expression of the protooncogenes, c-fos and c-myc, in muscle and liver of 14- and 19-day embryos and 1-, 6-, 8- and 28-day-old chicks of Athens Canadian Random Bred (ACRB) Single Comb White Leghorn (SCWL) and Peterson X Arbor Acres commercial broiler (PXAA) was determined. For the three stocks of chicken, significant differences were found in c-fos and c-myc expression. For both muscle and liver, averaged across ages, abundance of c-fos RNA was highest in PXAA and lowest in ACRB with differences significant at the P less than 0.01 level. c-myc RNA levels were significantly higher (P less than 0.01) in PXAA than in ACRB or SCWL liver. Taken over the developmental period, expression of c-fos RNA in muscle increased at different rates between breeds from 14-day embryo levels to peak levels in 6- to 8-day-old chicks and declined in 28-day-old chicks. Levels of c-fos were much lower in liver and showed no consistent differences related to developmental stage. A steady decline in c-myc from 14-day embryo levels to 28-day-old chicks was found in both muscle and liver. This decline in c-myc levels generally parallels the decline in relative growth rates which occurs in all breeds over the developmental period. In liver, the fast growing PXAA had the highest levels of c-myc, c-fos, on the other hand, showed elevated levels in PXAA for both muscle and liver and distinctly different patterns between these two tissues over the developmental period, suggesting tissue-specific involvement in growth. PMID- 1608402 TI - Nucleotide sequence and genomic structure analyses of the p70 subunit of the human Ku autoantigen: evidence for a family of genes encoding Ku (p70)-related polypeptides. AB - cDNA encoding the p70 polypeptide subunit of the human Ku autoantigen was isolated. In vitro expression analysis of the cDNA demonstrates that it encodes the entire open reading frame. Nucleotide sequence analysis and comparison to other previously described sequences indicate the existence of several single nucleotide and amino acid polymorphisms. Southern blot analyses demonstrate the presence of multiple copies of homologous DNA sequences in the human genome. These data support the hypothesis that multiple genes encode a family of Ku(p70) related polypeptides. PMID- 1608403 TI - Deletion analysis of the NH2-terminal region of beta-1,4-galactosyltransferase. AB - To determine the biological role, if any, of the NH2-terminal region of beta-1,4 galactosyltransferase (GT; EC 2.4.1.90), we constructed deletion mutants and expressed them in COS-7 cells. Each deletion construct was analyzed for enzymatic activity, protein production and mRNA transcription. All of the deletion mutants were transcribed to produce GT mRNA, but the GT protein was not detected in those constructs whose transmembrane (aa 14-42) domain was deleted. The results suggest that the transmembrane region is essential for the stability of the protein and perhaps contain sequences critical for the proper targeting of the molecule. The possible role of the NH2-terminal signal anchor domain in the in vivo regulation of GT is discussed. PMID- 1608404 TI - The effect of family relationships on adolescent development during family reorganization. PMID- 1608405 TI - Reactivation of unstable angina after the discontinuation of heparin. AB - BACKGROUND: Heparin is an effective, widely used treatment for unstable angina. Among patients enrolled in a double-blind, randomized, placebo-controlled trial comparing intravenous heparin, aspirin, both treatments, and neither during the acute phase of unstable angina, we encountered patients in whom unstable angina was reactivated after heparin was discontinued. METHODS: The study population included 403 of the original 479 patients in the trial who had completed six days of blinded therapy without refractory angina or myocardial infarction. After the discontinuation of therapy, clinical events, including reactivation of unstable angina and myocardial infarction occurring within 96 hours after hospitalization, were closely monitored. RESULTS: Early reactivation occurred in 14 of the 107 patients who received heparin alone, as compared with only 5 patients in each of the other three study groups (P less than 0.01). These reactivations required urgent intervention (thrombolysis, angioplasty, or coronary-bypass surgery) in 11 patients treated with heparin alone, but in only 2 patients in the other groups combined (P less than 0.01). Four of the six patients who had a myocardial infarction during a reactivation of their disease were in the heparin group. Reactivations in this group occurred in a cluster a mean (+/- SD) of 9.5 +/- 5 hours after the discontinuation of the study drug but were randomly distributed over the initial 96 hours in the other three groups. CONCLUSIONS: Although heparin is beneficial in treating unstable angina, the disease process may be reactivated within hours of the discontinuation of this drug. Concomitant therapy with aspirin may prevent this withdrawal phenomenon. PMID- 1608406 TI - Impairment of renal function with increasing blood lead concentrations in the general population. The Cadmibel Study Group. AB - BACKGROUND: Nephropathy is known to occur in persons with heavy exposure to lead. Whether exposure to lead in the general population leads to impaired renal function is not known. METHODS: We studied renal function and indexes of lead exposure in a random population sample of 965 men and 1016 women (age range, 20 to 88 years). In all the subjects we measured creatinine clearance and blood concentrations of lead and zinc protoporphyrin (an indirect measure of blood lead level). RESULTS: The mean (+/- SD) creatinine clearance rate was 99 +/- 30 ml per minute in the men and 80 +/- 25 ml per minute in the women. In the men the geometric mean blood lead concentration was 114 micrograms per liter (0.55 mumol per liter) (range, 23 to 725 micrograms per liter [0.11 to 3.5 mumol per liter]), and in the women 75 micrograms per liter (0.36 mumol per liter) (range, 17 to 603 micrograms per liter [0.08 to 2.9 mumol per liter]); the zinc protoporphyrin values in blood averaged 1.0 and 1.1 micrograms per gram of hemoglobin, respectively. The creatinine clearance rate was inversely correlated with blood lead and zinc protoporphyrin values in the men and the women both before and after adjustments for age, bodymass index, and diuretic treatment. A 10-fold increase in blood lead concentration was associated with a reduction of 10 to 13 ml per minute in creatinine clearance. We also found a positive correlation between serum beta 2-microglobulin (which is inversely related to the glomerular filtration rate) and blood lead in men, between serum beta 2-microglobulin and zinc protoporphyrin in both sexes, and between serum creatinine and zinc protoporphyrin in men. CONCLUSIONS: Exposure to lead may impair renal function in the general population. The alternative hypothesis that renal impairment may lead to an increase in the blood lead concentration cannot be excluded, however. PMID- 1608407 TI - Lack of efficacy of phenytoin in recessive dystrophic epidermolysis bullosa. Epidermolysis Bullosa Study Group. AB - BACKGROUND: Recessive dystrophic epidermolysis bullosa is an uncommon, severely disabling, heritable disorder characterized by abnormal fragility of the skin. Open trials have suggested that phenytoin is an effective treatment, and this therapy is now widely used. METHODS: To determine the efficacy of phenytoin in the treatment of recessive dystrophic epidermolysis bullosa, we performed a randomized, double-blind, placebo-controlled, crossover trial in 36 patients. Each treatment was given for five to seven months, separated by a two-month period. We measured the total number of blisters and erosions on the entire body, the size of three plaques containing blisters and erosions, and the number of blisters and erosions in the three plaques at the beginning and end of each treatment period in each patient. RESULTS: Twenty-two patients completed both courses of therapy, seven patients completed one course, and seven patients withdrew before completing a single course. There was no significant difference in disease activity between phenytoin treatment and placebo treatment, as measured by changes in the number of blisters and erosions on the entire body (7 percent decrease vs. 6 percent increase), in the area of three designated plaques (0.4 percent decrease vs. 0.2 percent increase), or in the number of blisters and erosions in the designated plaques (12 percent decrease vs. 31 percent increase). CONCLUSIONS: Phenytoin is not an effective treatment for patients with recessive dystrophic epidermolysis bullosa. PMID- 1608409 TI - Case records of the Massachusetts General Hospital weekly clinicopathological exercises. Case 29-1992. A 76-year-old woman with recurrent diarrhea several months after treatment for tropical sprue. PMID- 1608408 TI - A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes. AB - BACKGROUND: Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions. METHODS: We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed. RESULTS: Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups. CONCLUSIONS: An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents. PMID- 1608411 TI - Inherited and acquired blistering diseases. PMID- 1608410 TI - Thrombosis in unstable angina. PMID- 1608412 TI - Procedural safeguards for euthanasia. PMID- 1608413 TI - Procedural safeguards for euthanasia. PMID- 1608414 TI - Procedural safeguards for euthanasia. PMID- 1608416 TI - Procedural safeguards for euthanasia. PMID- 1608415 TI - Procedural safeguards for euthanasia. PMID- 1608417 TI - Procedural safeguards for euthanasia. PMID- 1608418 TI - High-osmolality and low-osmolality contrast agents. PMID- 1608419 TI - High-osmolality and low-osmolality contrast agents. PMID- 1608420 TI - High-osmolality and low-osmolality contrast agents. PMID- 1608421 TI - High-osmolality and low-osmolality contrast agents. PMID- 1608422 TI - Antibiotic prophylaxis and surgical-wound infections. PMID- 1608423 TI - Antibiotic prophylaxis and surgical-wound infections. PMID- 1608424 TI - Antibiotic prophylaxis and surgical-wound infections. PMID- 1608425 TI - Antibiotic prophylaxis and surgical-wound infections. PMID- 1608426 TI - Angioscopic evaluation of coronary-artery thrombi in acute coronary syndromes. PMID- 1608427 TI - Risk of cancer in dermatomyositis or polymyositis. PMID- 1608428 TI - Risk of cancer in dermatomyositis or polymyositis. PMID- 1608429 TI - Thalidomide to treat esophageal ulcer in AIDS. PMID- 1608430 TI - Subacute oral toxicity study of benzyl isothiocyanate in rats. AB - The subacute toxicity of benzyl isothiocyanate (BITC) was investigated in male rats given oral doses of 0, 50, 100 and 200 mg/kg body weight/day for 4 weeks. Body weight gain and food consumption were decreased with increasing doses of BITC. Haematological changes of toxicological relevance were observed in the highest dose group. BITC administration resulted in increased serum cholesterol level in all treatment groups and decreased serum triglycerides level at 200 mg/kg. Renal dysfunction was indicated by reduced urine volume, proteinuria and enhanced urinary lactate dehydrogenase activity. BITC exposure also affected the weights of various organs and caused histological changes in the ductus choledochus, liver, ileum and mesenteric lymph nodes. PMID- 1608431 TI - Direct determination of lead in cola beverages by electrothermal atomic absorption spectrophotometry (short communication). PMID- 1608432 TI - Influence of cooking on benzo(a)pyrene content in frankfurters (short communication). PMID- 1608433 TI - Sound embryo ruling. PMID- 1608434 TI - NIH laboratory admits to fabricated embryo research, retracts paper. PMID- 1608435 TI - Canada commits money for human genome research. PMID- 1608436 TI - Industry surprised by firm US stance on biodiversity treaty. PMID- 1608437 TI - New foundation to fund Russian biologists. PMID- 1608438 TI - Alternative toxicity tests. PMID- 1608439 TI - Fetal tissue. PMID- 1608440 TI - Reflections of a whistle-blower. AB - Scientific fraud, much in the news recently, is not a new phenomenon. What follows is a personal account of a particular case. PMID- 1608441 TI - RNA catalysis. The universe expands. PMID- 1608442 TI - Human origins. Genetics and geography. PMID- 1608443 TI - Healthy broccoli? PMID- 1608444 TI - Selfish genes in mosquitoes. PMID- 1608445 TI - Uncorrelated DNA walks. PMID- 1608446 TI - Human gene therapy comes of age. AB - Advances in the understanding of molecular biology of human disease and the development of efficient gene transfer techniques have resulted in practical approaches to human gene therapy, with new techniques being developed at an increasing rate. The first trials have now begun in humans and initial results are positive. PMID- 1608447 TI - X-ray analyses of peptide-inhibitor complexes define the structural basis of specificity for human and mouse renins. AB - X-ray analyses have defined the three-dimensional structures of crystals of mouse and human renins complexed with peptide inhibitors at resolutions of 1.9 and 2.8 A, respectively. The exquisite specificity of renin arises partly from ordered loop regions at the periphery of the binding cleft. Although the pattern of main chain hydrogen bonding in other aspartic proteinase inhibitor complexes is conserved in renins, differences in the positions of secondary structure elements (particularly helices) also lead to improved specificity in renins for angiotensinogen substrates. PMID- 1608448 TI - Segregation of global and local motion processing in primate middle temporal visual area. AB - The early stages of primate visual processing appear to be divided up into several component parts so that, for example, colour, form and motion are analysed by anatomically distinct streams. We have found that further subspecialization occurs within the motion processing stream. Neurons representing two different kinds of information about visual motion are segregated in columnar fashion within the middle temporal area of the owl monkey. These columns can be distinguished by labelling with 2-deoxyglucose in response to large-field random-dot patterns. Neurons in lightly labelled interbands have receptive fields with antagonistic surrounds: the response to a centrally placed moving stimulus is suppressed by motion in the surround. Neurons in more densely labelled bands have surrounds that reinforce the centre response so that they integrate motion cues over large areas of the visual field. Interband cells carry information about local motion contrast that may be used to detect motion boundaries or to indicate retinal slip during visual tracking. Band cells encode information about global motion that might be useful for orienting the animal in its environment. PMID- 1608449 TI - Targeting of cell-surface beta-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. AB - Progressive cerebral deposition of the amyloid beta-peptide is an early and invariant feature of Alzheimer's disease. The beta-peptide is released by proteolytic cleavages from the beta-amyloid precursor protein (beta APP), a membrane-spanning glycoprotein expressed in most mammalian cells. Normal secretion of beta APP involves a cleavage in the beta-peptide region, releasing the soluble extramembranous portion and retaining a 10K C-terminal fragment in the membrane. Because this secretory pathway precludes beta-amyloid formation, we searched for an alternative proteolytic processing pathway that can generate beta peptide-bearing fragments from full-length beta APP. Incubation of living human endothelial cells with a beta APP antibody revealed reinternalization of mature beta APP from the cell surface and its targeting to endosomes/lysosomes. After cell-surface biotinylation, full-length biotinylated beta APP was recovered inside the cells. Purification of lysosomes directly demonstrated the presence of mature beta APP and an extensive array of beta-peptide-containing proteolytic products. Our results define a second processing pathway for beta APP and suggest that it may be responsible for generating amyloid-bearing fragments in Alzheimer's disease. PMID- 1608450 TI - SWI6 protein is required for transcription of the periodically expressed DNA synthesis genes in budding yeast. AB - In budding yeast many genes are expressed under cell-cycle control in late G1. These include a large group of DNA synthesis genes, the HO gene involved in mating-type switching, CTS1 (chitinase) and also CLN1 and CLN2 (ref. 4) encoding G1 cyclins. Two factors, encoded by the SWI4 and SWI6 genes, are required for HO (ref. 5), CLN (refs 6, 7) and CTS1 (ref. 3) gene expression and, at least in the HO promoter, bind to CACGA4 upstream sequences (CCBs). This motif is not found upstream of the DNA synthesis genes, which instead have a hexamer element, ACGCGT1 (MCB), an MluI restriction site, that is recognized by a cell-cycle regulated transcription complex DSC1 (ref. 1). This MluI-activation system consisting of the MCBs and DSC1 is conserved in fission yeast where a DSC1-like complex controls the cdc22+ ribonucleotide reductase gene. The Schizosaccharomyces pombe cdc10+ gene encodes a component of DSC1 (ref. 10) and, significantly, this has homology with both the Swi4 and Swi6 proteins. Here we show that Swi6 is an essential component of DSC1 and that deletion of SWI6 impairs the cell-cycle regulation of the DNA synthesis genes, as well as CLN1 and CLN2. Thus Swi6 is the common factor in regulation of all the above genes and may therefore be responsible for the timing of their expression in late G1. PMID- 1608451 TI - A central role for SWI6 in modulating cell cycle Start-specific transcription in yeast. AB - Most genes involved in DNA replication in the yeast Saccharomyces cerevisiae are transcribed transiently during late G1 as cells become committed to a new cell cycle at Start. Their promoters all contain one or more versions of an 8-base pair motif (ACGCGTNA) containing an MluI restriction enzyme site and called the MluI cell-cycle box (MCB). MCBs are both necessary and sufficient for the late G1 specific transcription of the TMP1 thymidylate synthase and POL1 DNA polymerase genes. A different late G1-specific 8-base-pair transcription element called the SCB (CACGAAAA; ref. 5) is bound by a factor containing the Swi4 and Swi6 proteins. We describe here the formation in vitro of complexes on TMP1 MCBs that contain the Swi6 protein and, we suggest, a protein of relative molecular mass 120,000 (p120) that is distinct from Swi4. Transcription due to SCBs and MCBs occurs in the absence of Swi6 but it is no longer correctly regulated in the cell cycle. We suggest that Swi6 is an essential regulatory subunit of two different Start-dependent transcription factors. One factor (SBF) contains Swi4 and binds to SCBs, whereas the other (MBF) contains the protein p120 and binds MCBs. PMID- 1608452 TI - Functional contacts of a transfer RNA synthetase with 2'-hydroxyl groups in the RNA minor groove. AB - The functional analysis of determinants on RNA has been largely limited to molecules that contain naturally occurring ribonucleotides, so little is known about the role of 2'-hydroxyl groups in protein-RNA recognition. A single base pair (G3.U70) in the acceptor stem of tRNA(Ala) is the principal element for specific recognition by Escherichia coli alanine-tRNA synthetase. This tRNA synthetase aminoacylates small RNA helices that contain the G3.U70 base pair. Furthermore, removal of the G3 exocyclic 2-amino group that projects into the minor groove eliminates aminoacylation. This 2-amino group is flanked on either side by ribose 2'-hydroxyl groups that line the minor groove. Here we use chemical synthesis to construct 32 helices that make deoxy and O-methyl substitutions of individual and multiple 2'-hydroxyl groups near and beyond the G3.U70 base pair and find that functional 2'-hydroxyl contacts are clustered within a few angstroms of the critical 2-amino group. These contacts are highly specific and make a thermodynamically significant contribution to RNA recognition. PMID- 1608454 TI - Gene manipulation on plastic plates. PMID- 1608455 TI - Genome propaganda. PMID- 1608453 TI - Novel form of growth cone motility involving site-directed actin filament assembly. AB - Regulation of cytoskeletal structure and motility by extracellular signals is essential for all directed forms of cell movement and underlies the developmental process of axonal guidance in neuronal growth cones. Interaction with polycationic microbeads can trigger morphogenic changes in neurons and muscle cells normally associated with formation of pre- and postsynaptic specializations. Furthermore, when various types of microscopic particles are applied to the lamellar surface of a neuronal growth cone or motile cell they often exhibit retrograde movement at rates of 1-6 microns min-1 (refs 3-6). There is strong evidence that this form of particle movement results from translocation of membrane proteins associated with cortical F-actin networks, not from bulk retrograde lipid flow and may be a mechanism behind processes such as cell locomotion, growth cone migration and capping of cell-surface antigens. Here we report a new form of motility stimulated by polycationic bead interactions with the growth-cone membrane surface. Bead binding rapidly induces intracellular actin filament assembly, coincident with a production of force sufficient to drive bead movements. These extracellular bead movements resemble intracellular movements of bacterial parasites known to redirect host cell F-actin assembly for propulsion. Our results suggest that site-directed actin filament assembly may be a widespread cellular mechanism for generating force at membrane-cytoskeletal interfaces. PMID- 1608456 TI - US to seek gene patents in Europe. PMID- 1608457 TI - New French genome centre aims to prove that bigger really is better. PMID- 1608458 TI - Debate over animals is given a personal touch. PMID- 1608459 TI - A new kind of orphan drug? PMID- 1608460 TI - Science popularity stakes. PMID- 1608461 TI - CD8 and CD4. The box and the rod. PMID- 1608462 TI - Gene regulation. Ecdysone and the onion. PMID- 1608463 TI - Protein transport. Z and the insoluble answer. PMID- 1608464 TI - Proteins. One thousand families for the molecular biologist. PMID- 1608465 TI - Tumours and Coley's toxins. PMID- 1608466 TI - Chromosomal instability. PMID- 1608467 TI - Gustducin is a taste-cell-specific G protein closely related to the transducins. AB - A novel G protein alpha-subunit (alpha-gustducin) has been identified and cloned from taste tissue. alpha-Gustducin messenger RNA is expressed in taste buds of all taste papillae (circumvallate, foliate and fungiform); it is not expressed in non-sensory portions of the tongue, nor is it expressed in the other tissues examined. alpha-Gustducin most closely resembles the transducins (the rod and cone photoreceptor G proteins), suggesting that gustducin's role in taste transduction is analogous to that of transducin in light transduction. PMID- 1608468 TI - Involvement of the epidermal growth factor receptor in the invasion of cultured mammalian cells by Salmonella typhimurium. AB - Salmonella infection continues to be a major world-wide health problem. One essential pathogenic feature common to all Salmonella is their ability to penetrate the cells of the intestinal epithelium which are normally non phagocytic. The internalization of Salmonella into mammalian cells is thought to be a receptor-mediated phenomenon and the invasion of cultured epithelial cells depends on several Salmonella genes, but nothing is known about the host determinants participating in this interaction. Protein tyrosine phosphorylation follows stimulation of many cell-surface receptors to initiate signal transduction pathways that stimulate cellular responses. We report here that invasion of cultured Henle-407 cells by Salmonella typhimurium induces the tyrosine phosphorylation of the epidermal growth factor (EGF) receptor. In contrast, an isogenic strain of S. typhimurium that is defective in invasion owing to a mutation in the invA gene is unable to induce such phosphorylation. Addition of EGF to cultured Henle-407 cells allowed the internalization of the invasion-defective S. typhimurium invA mutant although it did not cause the internalization of an adherent, but non-invasive, strain of Escherichia coli. This result indicates that stimulation of the EGF receptor is involved in the invasion of cultured Henle-407 cells by S. typhimurium. PMID- 1608469 TI - Complementarity between sperm surface beta-1,4-galactosyltransferase and egg-coat ZP3 mediates sperm-egg binding. AB - Despite its importance, the molecular basis of mammalian gamete recognition has remained unclear. The enzyme beta-1,4-galactosyltransferase (Gal-transferase) has been viewed traditionally as a biosynthetic component of the Golgi complex, but is also found on the surface of many cells where it can bind its specific glycoside substrate on adjacent cell surfaces or in the extracellular matrix. In mouse it has been suggested that Gal-transferase on the sperm head mediates fertilization by binding oligosaccharide residues in the egg coat, or zona pellucida, and that the ability of the zona pellucida to bind sperm is conferred by oligosaccharides of the ZP3 glycoprotein. However, it has not been confirmed that Gal-transferase and ZP3 are in fact complementary gamete receptors whose interaction mediates sperm-egg binding. Here we show that mouse sperm Gal transferase specifically recognizes those oligosaccharides on ZP3 that have sperm binding activity, but does not interact with other zona pellucida glycoproteins. In contrast, all zona pellucida glycoproteins are recognized by non-sperm Gal transferase, demonstrating a more stringent substrate specificity for the sperm enzyme. This interaction is required for sperm-egg binding because blocking or removing the binding site for Gal-transferase on ZP3 inhibits its ability to bind sperm. After the release of the sperm acrosome, the transferase relocalizes to a new membrane domain where it can no longer bind to ZP3, which is consistent with the inability of acrosome-reacted sperm to bind ZP3 or to initiate binding to the zona pellucida. Following fertilization, ZP3 is modified by egg cortical granule secretions so that it loses sperm receptor activity, which can be accounted for by a selective loss of its binding site for sperm Gal-transferase. These results show that sperm surface beta-1,4-galactosyltransferase and the egg-coat glycoprotein ZP3 are complementary adhesion molecules that mediate primary gamete binding in the mouse. PMID- 1608470 TI - Antigen presentation enhanced by the alternatively spliced invariant chain gene product p41. AB - During biosynthesis, class II molecules of the major histocompatibility complex are associated with a nonpolymorphic protein called invariant chain, Ii, which facilitates folding of class II molecules and their exit from the endoplasmic reticulum, interferes with their association with peptide and directs their post Golgi transport (refs 7-9). If Ii blocks class II loading with endogenous antigens in the endoplasmic reticulum and/or directs class II molecules to the exogenous antigen-loading compartment, then the co-expression of Ii should enhance the ability of class II molecules to present exogenous antigens to T cells. But data supporting a role for Ii in class II-restricted antigen presentation are controversial. Here we show that Ii can facilitate exogenous antigen presentation for a subset of antigens. Although all known functions of Ii have been ascribed to the principal form of Ii, p31, we find that in most cases antigen presentation is facilitated only by the alternatively spliced, minor form of Ii, p41. PMID- 1608471 TI - Ca2+ release induced by inositol 1,4,5-trisphosphate is a steady-state phenomenon controlled by luminal Ca2+ in permeabilized cells. AB - Low concentrations of inositol 1,4,5-trisphosphate (InsP3) evoke a very rapid mobilization of intracellular Ca2+ stores in many cell types, which can be followed by a further, much slower efflux. Two explanations have been suggested for this biphasic release. The first proposes that the Ca2+ stores vary in their sensitivity to InsP3, and each store releases either its entire contents or nothing (all-or-none release); the second proposes instead that the stores are uniformly sensitive to the effects of InsP3, but that they can release only a fraction of their Ca2+ before their sensitivity is somehow attenuated (steady state release). Experiments using purified InsP3 receptor molecules reconstituted into lipid vesicles have shown heterogeneity of the receptors in their response to InsP3 under conditions in which the total Ca2+ level at both sides of the receptor is held constant. We now report that in permeabilized A7r5 smooth-muscle cells incubated in Ca(2+)-free medium, the amount of 45Ca2+ remaining in the stores after the rapid transient phase of release is independent of their initial Ca2+ levels, indicating that partially depleted stores are less sensitive to InsP3. Moreover, if the stores are reloaded with 40Ca2+ after the first stimulus, reapplication of the same low concentration of InsP3 will release further 45Ca2+. This recovery of InsP3 sensitivity is almost complete. Under these conditions, Ca2+ release must thus occur by a steady-state mechanism, in which the decreasing Ca2+ content of the stores slows down further release. PMID- 1608472 TI - Involvement of p21ras in activation of extracellular signal-regulated kinase 2. AB - Many growth factors upon stimulation of their receptors induce the activity of extracellular signal-regulated kinases, ERKs, also known as MAP kinases. Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form. We have shown that direct introduction of p21ras oncoprotein into cells in the absence of growth factors activates ERKs within five minutes, which indicates that normal p21ras may be involved in the activation of ERKs by growth factors. Here we use a recombinant vaccinia virus expressing an interfering mutant of p21ras, RasAsn17, to investigate this question. In NIH3T3 cells that overexpress the insulin receptor, this recombinant virus inhibits insulin-induced activation of ERK2 completely, but there is no inhibition of insulin-induced activation of phosphatidylinositol-3-kinase. In rat 1 cells the recombinant virus inhibited ERK2 activity induced by platelet-derived growth factor (PDGF) but not by phorbol ester. We conclude that p21ras mediates insulin- and PDGF-induced activation of ERK2. PMID- 1608474 TI - Beyond silver staining. PMID- 1608475 TI - The importance and use of iron supplementation in uremia. PMID- 1608473 TI - The mechanism of Z alpha 1-antitrypsin accumulation in the liver. AB - Most northern Europeans have only the normal M form of the plasma protease inhibitor alpha 1-antitrypsin, but some 4% are heterozygotes for the Z deficiency variant. For reasons that have not been well-understood, the Z mutation results in a blockage in the final stage of processing of antitrypsin in the liver such that in the Z homozygote only 15% of the protein is secreted into the plasma. The 85% of the alpha 1-antitrypsin that is not secreted accumulates in the endoplasmic reticulum of the hepatocyte; much of it is degraded but the remainder aggregates to form insoluble intracellular inclusions. These inclusions are associated with hepatocellular damage, and 10% of newborn Z homozygotes develop liver disease which often leads to a fatal childhood cirrhosis. Here we demonstrate the molecular pathology underlying this accumulation and describe how the Z mutation in antitrypsin results in a unique molecular interaction between the reactive centre loop of one molecule and the gap in the A-sheet of another. This loop-sheet polymerization of Z antitrypsin occurs spontaneously at 37 degrees C and is completely blocked by the insertion of a specific peptide into the A-sheet of the antitrypsin molecule. Z antitrypsin polymerized in vitro has identical properties and ultrastructure to the inclusions isolated from hepatocytes of a Z homozygote. The concentration and temperature dependence of this loop-sheet polymerization has implications for the management of the liver disease of the newborn Z homozygote. PMID- 1608476 TI - Transplant recipients and donor families: should they meet? PMID- 1608477 TI - Future trends and issues in erythropoietin. Part II. AB - Although recombinant human erythropoietin (rHuEPO) has only been approved for clinical use since 1989, its beneficial effects in the treatment of anemia in patients with chronic renal failure has been clearly demonstrated. Bolstered by this success, clinical investigators are now turning to other types of anemia that might benefit from such therapy. Part II of this article will continue to discuss some of the potential areas of clinical application for rHuEPO. Part I was published last month in NN&I. PMID- 1608478 TI - How to influence the politics/medicine game. PMID- 1608479 TI - [Is pneumonia of unknown origin yet a pneumococcal pneumonia sometimes?]. PMID- 1608480 TI - [The Dutch infant mortality in the 80s]. PMID- 1608481 TI - [Intravascular echography]. PMID- 1608482 TI - [Pneumococcal pneumonia with a fulminant course]. AB - Four patients admitted with a pneumococcal pneumonia are described. Well-known risk factors such as immunodeficiency or preexisting cardiopulmonary problems were absent. They had been ill for three to five days and had not been treated with antibiotics. Three patients died; upon admission these had extensive pulmonary infiltrates (two or more lobes affected), respiratory insufficiency necessitating mechanical ventilation, and shock at or soon after admission. The prognosis of pneumococcal pneumonia with a fulminant course has not improved in the last few decades despite proper antibiotics and intensive care treatment. Mortality is over fifty percent. Early recognition and treatment can contribute to a better prognosis. PMID- 1608483 TI - [Comparison of 2 scales in the assessment of injury severity in seriously injured patients]. AB - We compared the Abbreviated Injury Scale (AIS-85) and the Hospital Trauma Index (HTI) in seriously injured patients. The effect of these scales on the application of Injury Severity Scores (ISS) was investigated. Furthermore, the predictive value on mortality of the AIS/ISS and the HTI/ISS was determined. Subjects were 932 seriously injured patients (HTI/ISS score greater than or equal to 18) admitted to University Hospital Groningen between 1985 and 1990. A quantitative and a qualitative comparison were performed. Logistic regression was used to estimate the predictive value of the AIS/ISS and the HTI/ISS on mortality. The AIS/ISS and HTI/ISS differed quantitatively and qualitatively. The average HTI/ISS score was ten points higher than the average AIS/ISS. By combining specific regions of the scales the predictive value could be improved. The ISS scores were incomparable. Consequently in future studies the method used to calculate the ISS score should be mentioned. PMID- 1608484 TI - [Pain in rheumatoid arthritis measured with the visual analogue scale and the Dutch version of the McGill Pain Questionnaire]. AB - Chronic pain is an important symptom of rheumatoid arthritis (RA). Pain is a complex experience and is not easily measured with a single instrument. Recently a Dutch version of the McGill Pain Questionnaire (MPQ) became available. The MPQ is a measure of the quality of pain as opposed to the traditional measures of pain intensity such as the Visual Analog Scale (VAS). In a study of 415 RA patients both measures of pain were administered. Both pain measures were only weakly related to medical variables. The VAS is easily administered and is reliable. The MPQ offers insight in the sensory experience of pain and gives more information about the quality of life of the patient. The conclusion is that the MPQ is a useful instrument to obtain a better picture of the complexity of the pain experience in RA. PMID- 1608485 TI - [Chronic diseases from the viewpoint of management and science]. PMID- 1608486 TI - [Sleeping poorly due to sedatives (rebound insomnia) and the role of zopiclone]. PMID- 1608487 TI - [Intermittent claudication in young patients]. PMID- 1608488 TI - Incidence of multiple sclerosis in Denmark 1948-1982: a descriptive nationwide study. AB - The incidence rates of multiple sclerosis (MS) in Denmark were estimated as a result of a continuous nationwide epidemiological survey since 1948 by the Danish Multiple Sclerosis Registry (DMSR). Among cases notified to the DMSR, 6,478 met the diagnostic criteria and had onset of MS from 1948 through 1982. The crude annual incidence rate was 4.45/100,000 and the lifetime cumulative incidence rate was 0.32%. The female/male ratio was 1.37:1. Crude incidence rates declined during the period 1952-1967. After 1967 the incidence seemed to rise again but in an irregular pattern. The decline in incidence involved only cases up to the age of 35. The subsequent increase was most marked in females and in the age groups over 45 years. PMID- 1608489 TI - Prevalence of multiple sclerosis in the city of Sao Paulo, Brazil, in 1990. AB - A case register of multiple sclerosis (MS) was set up in the city of Sao Paulo, Brazil, situated at a latitude of 23-24 degrees south. Cases were notified by neurologists, neuroradiologists and by an association of patients with MS. Prevalence rate was 4.27 x 10(-5) (men: 2.89 x 10(-5); women: 5.59 x 10(-5)), with a preponderance of young adults. We discuss here whether these rates are artifact due to poor health care facilities, to poor notification and deficiencies in diagnosis, or whether these rates are really low. PMID- 1608490 TI - Stroke in China (Sino-MONICA-Beijing study) 1984-1986. AB - We present here the results of the Sino-MONICA-Beijing stroke study based on 700,000 Beijing residents in 1984-1986. To compare incidence rates for stroke with other communities and countries, we adopted the criteria of the WHO Collaborative Study of 17 centers which used the same definition and methodology as was used in this study. Over the 3-year period of the study, 2,593 stroke events were registered in the 25- to 74-year age-group. The incidence rate for all strokes was 189.5/100,000 and the incidence rate for first strokes was 133.6/100,000. Men had a significantly higher incidence rate than women (all strokes 219.7/100,000 for male vs. 160.5/100,000 for female, OR = 1.32, 99% limits 1.19-1.46; first strokes 151.6/100,000 for male vs. 116.4/100,000 for female, OR = 1.25, 99% limits 1.11-1.42). In comparison with other studies, age adjusted incidence rate of stroke in Beijing was higher than in other countries, especially for hemorrhagic stroke. The proportion of hemorrhagic stroke related to other types of stroke was also higher in Beijing. Further analysis of the cases confirmed by computerized tomography also supported this finding. Unlike the incidence rates, the 4-week case fatality rate for women, 39.5%, was higher than for men, 32.8%. This finding was confirmed by a multiple logistic analysis controlling for age (p less than 0.001) and for previous stroke (p less than 0.001). The adjusted sex difference is also significant (OR = 1.37, p less than 0.001). In addition, results showed that men had a higher hospitalization rate than women. More women than men were treated at home, possibly indicating better medical care for men. PMID- 1608491 TI - Risk factors for ischemic stroke: a case control analysis. AB - Case control analysis of 204 patients with acute ischemic stroke revealed the matched pair odds ratio (and 95% confidence limits) for hypertension, ECG abnormality, heart disease of any type, diabetes, smoking and alcohol intake to be 3.95 (2.5, 6.2), 2.1 (1.4, 3.1), 2.1 (1.4, 3.2), 1.7 (1.1, 2.6), 1.8 (1.1, 2.8) and 1.5 (0.86, 2.6), respectively. Except alcohol intake, the other factors were statistically significant. Hemoglobin, packed cell volume (hematocrit), serum cholesterol, triglycerides and low-density lipoprotein cholesterol levels were not found to be significant. High-density lipoprotein (HDL) cholesterol and uric acid were significantly lower and the ratio of total cholesterol to HDL cholesterol (TC/HDL) was higher among stroke patients. The risk was considerably higher when there was any combination of hypertension, heart disease and HDL cholesterol level lower than 45 mg/dl. Logistic regression revealed hypertension, heart disease of any type, lower HDL cholesterol and uric acid and higher ratio of TC/HDL to be significant factors. PMID- 1608492 TI - Influence of transient ischemic attack or small stroke on cessation of smoking. AB - A retrospective follow-up study was performed on a cohort, which took part in a secondary prevention trial after transient ischemic attack (TIA) or small stroke, to study variables relevant to the cessation of smoking. Of 100 patients, 57 smoked, 1 was lost to follow-up and 18 stopped smoking. Age, gender, amount of cigarettes, hospital admission, and persistence of symptoms were not statistically significant factors in the cessation of smoking in this group, which reported regularly for follow-up in the Dutch TIA trial. Directly after the event 11 patients stopped indefinitely and another 18 patients tried, but resumed smoking later on. During follow-up another 7 stopped. The important factor in the cessation of smoking was the event itself, as most people stopped directly after it, but enforcement was difficult, as half of those who stopped resumed smoking. PMID- 1608493 TI - Epidemiology of spinal muscular atrophies in a sample of the Italian population. AB - In the course of an epidemiological survey in four provinces of Veneto (northeastern Italy) 67 spinal muscular atrophy (SMA) cases (types I, II and III) were recorded. The survey spanned the period 1960-1983 and involved 859,891 consecutive live-born infants in a population of 2,635,800 inhabitants. The overall prevalence at birth for SMA types I, II and III was 7.8/100,000 live births. Type I alone accounted for 4.1/100,000 live births. If the hypothesis that SMA types I, II and III are clinical manifestations of allelic mutations is assumed, the mutation rate would be about 70 x 10(-6) and the frequency of the heterozygotes 1 in 57. PMID- 1608494 TI - Italian Multicenter Study on Dementia: a protocol for data collection and clinical diagnosis of Alzheimer's disease. The SMID Group. AB - This paper describes a protocol for identifying patients suspected of having Alzheimer's disease (AD) which was used in a long-term multicenter study in Italy. It relies on a progressive elimination procedure to arrive at a clinical diagnosis of 'very probable AD', with a sensitivity of 0.96 in terms of 2 years follow-up data. PMID- 1608495 TI - Familial migraine in a Mexican population. AB - We investigated the frequency of migraine in first-degree relatives of a group of migraine patients in two Mexican populations, one urban and one rural, and in control groups from the same populations. In the urban population, familial aggregation of migraine was found in 52.7% of patients and in the rural in 38.7%. The differences between controls and subjects were statistically significant in both populations. Our findings support the importance of a hereditary factor in migraine but not an autosomal dominant inheritance pattern. PMID- 1608496 TI - A randomized clinical trial of the efficacy and safety of the treatment of the first unprovoked epileptic seizure. First Seizure Trial Group. PMID- 1608497 TI - Prevalence of multiple sclerosis: a door-to-door survey in Lan Cang La Hu Zu Autonomous County, Yunnan Province of China. PMID- 1608498 TI - [Rifampicin protocol--protamine administered by central venous catheters in hemodialysis]. PMID- 1608499 TI - Hypertension in the elderly American: current approach in the USA. PMID- 1608500 TI - [Creatinine and renal function]. AB - Serum creatinine remains the most widely used measure of renal function in clinical practice and in clinical trials. However, the serum concentration reflects not only renal excretion, which is composed of filtration and tubular secretion, but also the generation, intake, and metabolism of creatinine. Thus, serum creatinine does not provide an adequate estimate of glomerular filtration rate (GFR). Creatinine clearance is also an inaccurate and imprecise measure of GFR in clinical practice. The questions concerning the abnormality or the change of glomerular function can be answered with greater accuracy and precision by serum creatinine if the factors affecting its concentration are taken into account. The slope of the decline in reciprocal serum creatinine versus time does not accurately reflect changes in creatinine clearance and does not allow an accurate assessment of the rate of progression of renal disease. It can even be hazardous to use such value to observe the efficacy of treatments for progressive renal diseases. PMID- 1608501 TI - [Respective role of the size, location and composition of the calculus as determinants of therapeutic success after extracorporeal shock wave lithotripsy in renal lithiasis]. AB - We evaluated the respective role of size, location and composition of renal stones as determinants of the outcome of extracorporeal shock wave lithotripsy (ESWL). The analysis of the chemical composition and of the morphology of the fragments eliminated by hundred patients who underwent ESWL has been made by X rays diffraction. Results showed that the larger the stone, the higher the risk of having to perform an extra intervention (additional sessions of ESWL, percutaneous nephrostolithotomy, nephrolitholapaxy) or of finding residual fragments at the three month check-point. In addition, the location of the stone in a calice, especially a lower calice, strongly predisposes to incomplete elimination of the fragments. Finally, two types of stones appear to lessen the probability of success of ESWL: those of struvite and those of cystine. Indeed, out of eleven ESWL performed on struvite stones (pure or mixed), two had to be completed by percutaneous nephrolitholapaxy and even one by a nephrectomy because of superinfection. Out of the four patients with cystine stones, two had to be treated by additional percutaneous nephrolitholapaxy because of inadequate fragmentation after ESWL. However, for the remaining types of stones (pure or mixed) chemical composition seems to be less important than size or location. PMID- 1608502 TI - [Comparison of the efficacy and tolerance of recombinant human erythropoietin between intravenous and subcutaneous administration in chronic hemodialysis. Prospective multicenter study]. AB - The efficacy and tolerance of intravenous and subcutaneous administrations of recombinant human erythropoietin (r-HuEPO) have been compared in 50 maintenance hemodialysis patients. A 2 month course of intravenous r-HuEPO given at stable dosage was followed by a 6 month course of subcutaneous r-Hu EPO. We reduced r HuEPO dosage by 50% when starting subcutaneous administration and regularly adapted the dosage to achieve hematocrit levels between 30 and 35%. At the end of the study, mean r-HuEPO dosage was 82 +/- 8 (mean +/- SEM) IU/kg/week, which represented 70 +/- 7% of intravenous r-HuEPO dosage. Mean hematocrit value was 32.9 +/- 0.5% when starting subcutaneous administration and also at the end of this study. Arterial blood pressure remained stable over the whole trial period as did most biological blood tests which were not influenced by the route of administration. In 98% of cases, patients expressed either pain-free (50%) or slight to moderate pain (48%) at the injection site. This trial confirms a substantial dosage economy when using r-HuEPO by subcutaneous route rather than by intravenous route. Moreover, objective and subjective tolerance was excellent on r-HuEPO subcutaneous administration. PMID- 1608503 TI - [Which index to choose for quantification of the adequacy of filtration method in the hemodialysis patient?]. AB - On the basis of a retrospective re-analysis of the data from the National Cooperative Dialysis Study, Sargent and Gotch have proposed the normalized index KT/V as an index of the level of dialytic therapy. However the current methods of calculating KT/V are complex for routine clinical use and require great care in order to avoid major inaccuracies on the estimation of dialyzer urea clearance and the subsequent calculation of the volume of distribution of urea. As the pre to post-dialytic plasma urea ratio C0/CF is a function of dialyzer urea clearance, duration of dialysis and urea distribution volume of the patient, it might well correlate with KT/V. The simplified index I = 1.2 x ln (C0/CF) is well correlating (r = 0.9; n = 15) and well approximating (3%) with KT/V and with other indexes derived from various formulas. Consequently the use of this index is electively proposed for routine determination of the quantification of dialysis. PMID- 1608504 TI - [New findings on the complement system in nephrology]. PMID- 1608505 TI - Increased angiotensin-(1-7) in hypophysial-portal plasma of conscious sheep. AB - Studies were undertaken to characterize angiotensin peptides in hypophysial portal blood of conscious sheep and to determine whether the median eminence (ME) secretes angiotensin peptides into the hypophysial-portal circulation. Simultaneous measurements of angiotensin peptides in jugular and hypophysial portal plasma were performed in 6 sheep. Cerebrospinal fluid (CSF) was collected and data for hypophysial-portal plasma were corrected for CSF contamination. Angiotensin peptides were also measured in extracts of sheep ME. In a separate group of 4 sheep, simultaneous measurements of angiotensin peptides in arterial and jugular plasma were performed. Using high performance liquid chromatography based radioimmunoassays, 8 angiotensin peptides were measured: Ang-(1-7), Ang II, Ang-(1-9), Ang I, Ang-(2-7), Ang III, Ang-(2-9), and Ang-(2-10). Renin, angiotensinogen and prolyl endopeptidase were also measured. No differences in angiotensin peptide levels in arterial and jugular plasma were observed. Angiotensin peptide levels in hypophysial-portal plasma were similar to those in jugular plasma, except for Ang-(1-7), the levels of which were 5-fold higher in hypophysial-portal plasma, and Ang I, for which the levels in hypophysial-portal plasma were 46% of the jugular levels. Renin and angiotensinogen levels were similar in arterial, jugular, and hypophysial-portal plasma. Angiotensin peptide contents of sheep ME were less than 16 fmol/ME. However, the prolyl endopeptidase content of sheep ME was 430-fold higher than plasma levels. The low levels of angiotensin peptides in sheep ME indicate that it does not secrete these peptides into the hypophysial-portal circulation. Rather, the high level of prolyl endopeptidase in ME is consistent with region-specific metabolism of Ang I delivered to the ME by arterial blood, generating increased levels of Ang-(1-7) in hypophysial portal plasma. The increased levels of Ang-(1-7) in hypophysial portal plasma may play a role in regulation of pituitary function. PMID- 1608506 TI - Immuno-reactive and bioactive corticotropin-releasing factor in rat thymus. AB - Immunoreactive corticotropin-releasing factor (CRF) was identified and measured by radioimmunossay in rat thymic extract. Serial dilutions of thymic extract paralleled hypothalamic extract and synthetic CRF standard curves. CRF extracted from rat thymus eluted in the position of synthetic rat CRF on Sephadex G-25 column. Thymus-derived CRF was biologically active as demonstrated by stimulating adrenocorticotropic hormone secretion in dispersed rat anterior pituitary cells. These findings indicate the presence of authentic CRF in rat thymus, further supporting the concept of an integrated regulation of the neuroendocrine-immune responses to environmental stimuli. PMID- 1608507 TI - Perinatal hypothyroidism decreases hippocampal mossy fiber zinc density in rats. AB - The effect of perinatal hypothyroidism on hippocampal mossy fiber zinc density was examined in rats. Timed pregnant Sprague-Dawley rat dams were given water containing either 0.02% propylthiouracil (PTU) or vehicle from gestational day 18 until their litters were weaned on postnatal day 31. Hippocampal mossy fiber zinc density was reduced by 75% in both the dorsal and ventral hippocampal formation CA3 stratum lucidum region of 31-day-old PTU-treated rats compared to untreated controls. Perinatal hypothyroidism did not alter hippocampal tissue zinc concentration, indicating that the PTU-induced reduction in mossy fiber zinc was not a consequence of reduced hippocampal zinc concentration. At 120 days of age, 3 months after discontinuation of PTU treatment, hippocampal mossy fiber zinc density remained significantly reduced by 33-45% in PTU-treated rats compared to control. These data indicate that perinatal hypothyroidism causes a long-lasting reduction in hippocampal mossy fiber zinc density. PMID- 1608508 TI - Mechanism of intrahippocampal neostigmine-induced hyperglycemia in fed rats. AB - We previously reported that the injection of neostigmine, an acetylcholine esterase inhibitor, into the dorsal hippocampus produced hepatic venous plasma hyperglycemia associated with an increase of epinephrine and glucagon in anesthetized fed rats. To evaluate the relative contribution of these glucoregulatory hormones and the nervous system to the net hyperglycemic response, we unilaterally injected neostigmine (5 x 10(-8) mol) into the dorsal hippocampus in the following groups of rats: intact rats with bilateral adrenalectomy to eliminate the action of epinephrine, and rats receiving a constant infusion of somatostatin and insulin to prevent the glucagon response and to maintain the basal insulin level. Hepatic venous plasma levels of glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine were determined. The area under the glucose curve during the 120-min period following the injection of neostigmine was compared between groups. The areas under the glucose curve for rats receiving somatostatin and insulin, adrenalectomy rats, and adrenalectomy rats receiving somatostatin and insulin were, respectively, 82, 31, and 61% of that for intact rats. The fashion of hippocampal stimulated hyperglycemia with neostigmine was similar to that after injection of neostigmine into the third cerebral ventricle. Therefore, we investigated hyperglycemia in rats with lesions of ventromedial hypothalamus and found that the response to hippocampal neostigmine was significantly inhibited by the hypothalamic lesion. These findings suggest that the glucoregulatory hippocampal activity evoked by neostigmine may be transmitted to peripheral organs via the ventromedial hypothalamus. PMID- 1608509 TI - Thyroid hormones regulate release and content of vasoactive intestinal peptide in cultured fetal cerebral cortical cells. AB - The effects of thyroid hormones (TH) on brain immunoreactive-vasoactive intestinal peptide (IR-VIP) secretion and content in cultured fetal rat cortical cells were studied. Cerebral cortical cells were maintained as monolayer cultures for 14-18 days. T3 or T4 (10(-7) M) caused a time-dependent decrease in total IR VIP. Significant suppression was observed following treatment periods of 6 h or longer (24 and 48 h). Depending on the length of time cells had been deprived of TH prior to the addition of exogenous T3 or T4, these two thyroid hormones had different effects on IR-VIP accumulation. Both T3 and T4 caused a dose-dependent suppression or IR-VIP accumulation when there was no deprivation period or when it lasted 4 h. However, a biphasic effect was observed when cells were deprived of TH for 17 and 24 h: low doses of T3 or T4 (from 10(-12) to 10(-10) M) significantly increased (p less than 0.05) total IR-VIP, while high T3 or T4 doses (10(-8) and 10(-7) M) caused a significant decrease (p less than 0.01). The TH action was furthermore shown to be reversible. After T3 (10(-7) M) removal and subsequent incubation in serum-free medium for 6, 24 and 48 h, T3-treated and control cells exhibited similar levels of IR-VIP release and content. At this time, a new exposure to T3 (10(-7) M) again had a suppressive effect.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608510 TI - Fetal development of delta-sleep-inducing-peptide-like immunoreactivity in hypothalamus of guinea pig with special regard to the prenatal colocalization with gonadotropin-releasing-hormone-like immunoreactivity. AB - Delta-sleep-inducing peptide (DSIP) colocalizes within gonadotropin-releasing hormone (GnRH)-containing neurons in adult hypothalamus and could play a role in the regulation of hypothalamic-pituitary axis in adults. To support the possibility that DSIP also participates in fetal neuroendocrine events and to demonstrate the ontogenic evidence of coexisting neuropeptides, we have performed a detailed immunocytochemical study of DSIP- and GnRH-immunoreactivity in fetal hypothalamus of guinea pig. Using indirect immunofluorescent and sequential double-immunolabeling (elution-restaining) techniques, the results indicated that DSIP immunoreactivity was initially detected at the 38th day of gestation. In contrast to the first appearance of GnRH immunoreactivity at day 28, therefore, a 10-day delay was found. Such a delay remains as yet unexplained. From its first occurrence, DSIP immunoreactivity was always labeled with GnRH, whereas some of GnRH-immunoreactive structures did not display a DSIP immunoreactivity. But with the growth of fetus, especially before and after birth, a complete overlap between DSIP and GnRH immunoreactivity was observed throughout various regions of hypothalamus. Attention was also focused on prenatal morphological development of DSIP/GnRH- and GnRH-immunolabeled neurons. Initially, labeled neurons were visualized as uni- or bipolar types. Thereafter, their smooth and irregular subtypes could be distinguished. During later fetal age, relatively mature features were evident such as the increase of multipolar and irregularly labeled neurons. Taken together, these data provide, for the first time, anatomical evidence that DSIP exists in fetal hypothalamus and that, like GnRH, it could regulate the hypothalamic-pituitary axis during ontogenesis. PMID- 1608511 TI - Developmental changes in the uptake of testosterone by the primate brain. AB - During the neonatal period in male macaques, the testis produces adult-like levels of plasma testosterone (T), but the function of this in development is not understood. To investigate the interaction of T with the neonatal brain, 4 male and 5 female cynomolgus monkeys were gonadectomized 2-5 days after birth, and were injected subcutaneously 3 days later with 500 microCi [3H]-testosterone ([3H]-T). 60 min later, brains and other tissue samples were removed. Purified nuclear pellets were prepared by centrifugation through 2 M sucrose, extracted into ether and analyzed by high-performance liquid chromatography. The aromatized metabolite, [3H]-estradiol [( 3H]-E2), was found only in the hypothalamus (HYP) and amygdala (AMG). In HYP, [3H]-E2 represented 55 +/- 3% of the radioactivity in males and 53 +/- 3% in females. In AMG, [3H]-E2 represented 40 +/- 9% of the radioactivity in males and 47 +/- 3% in females. Concentrations of unchanged [3H] T were higher than those of [3H]-dihydrotestosterone [( 3H]-DHT). Both androgens were present in nuclear pellets from all 8 brain regions studied, and concentrations were significantly higher in females than in males (p less than 0.005). [3H]-T was also the main form of radioactivity in nuclear pellets from pituitary gland, adrenal gland, uterus and liver, but very high levels of [3H] DHT were found in seminal vesicles, prostate and penis. Comparisons were made with previous results from orchidectomized fetuses at 122 days gestation and from fully adult male castrates, and the largest developmental changes occurred in the AMG where concentrations of [3H]-E2 were 20-fold higher in adults than in fetuses, and most of this increase took place after the neonatal stage. Nuclear concentrations of [3H]-T also increased markedly during development in most brain regions except the cerebellar cortex where they declined. PMID- 1608512 TI - Identification of dopamine and growth hormone-releasing factor-containing neurons projecting to the median eminence of the rat by combined retrograde tracing and immunohistochemistry. AB - The topographical location of tyrosine hydroxylase (TH) neurons, a marker for dopamine neurons in the hypothalamus, that project to the median eminence was identified with immunofluorescence staining in combination with retrograde transblue, indicating that they projected to the median eminence. Only a few retrogradely labeled TH cells were observed in the periventricular nucleus and the lateral basal hypothalamus. The elution restaining procedure revealed that an average of 32% of the labeled TH cells in the ventrolateral portion of the ARC contained GRF. These findings support the hypothesis of co-expression of dopamine with GRF from the ARC. PMID- 1608513 TI - Socioemotional transformations in the family system following infant crawling onset. PMID- 1608514 TI - Emotional distress and control in young children. PMID- 1608515 TI - Emotional responsivity to others: behavioral correlates and socialization antecedents. AB - We have proposed that how children deal with emotional arousal in social situations affects the quality of their social interactions. More specifically, we have argued that children who can regulate negative emotions so that they are not overly aroused interact in more adaptive ways. Based on these assumptions, we have started to examine the relations of parental characteristics and practices to children's emotional responding and social behavior. Initial research findings provide partial support for the conclusion that parental encouragement of children's expression of their own sadness, distress, and sympathy, as well as parental practices that teach children ways to deal with negative emotion eliciting situations and their own negative emotions, are associated with sympathetic emotional responding and with adaptive social behavior. These findings suggest that further examination of the ways in which children learn to manage their emotions in social interactions will serve to augment our understanding of the socialization of social competence. PMID- 1608516 TI - Self-regulation and emotion in infancy. PMID- 1608517 TI - Children's affective responses to the expressive cues of others. PMID- 1608518 TI - [Diagnostic and therapeutic aspects of endometrial polyps]. AB - The diagnostic and therapeutic utility of hysteroscopy in intracavity uterine pathologies is now widely recognised. The Authors have evaluated the efficacy of hysteroscopy in 640 patients in a study of endometrial polyps for which the endoscopic technique represents the elective form of therapy, avoiding excessive trauma to the patient and preserving the endometrial mucosa intact. The results obtained are fully discussed. Hysteroscopic resection of polyps was carried out in 49 patients in a day-hospital setting and without further complications. PMID- 1608519 TI - [Hysteroscopic diagnosis in patients with abnormal uterine hemorrhage and previous endometrial curettage]. AB - Thirty-four patients, with a history of persistent abnormal uterine bleeding and dilatation and curettage or suction curettage performed within the previous year, were evaluated by office hysteroscopy and biopsy. For 16 patients (47%) the hysteroscopic diagnosis was in agreement with the curettage. Hysteroscopy revealed more information in 18 patients (53%): 8 had polyps, 6 had submucous or pedunculated myoma, 2 had endometrial neoplasia, 1 had myoma and polyp, 2 had endometrial neoplasia and 1 had synechia. Moreover in 3 patients with diagnosis of suspected myoma by curettage, hysteroscopy revealed a normal cavity. The high incidence of missed diagnosis of pathologic conditions by "blind" curettage supports the opinion that diagnostic hysteroscopy is the method of choice in the evaluation of abnormal uterine bleeding. PMID- 1608520 TI - [Systemic lupus erythematosus in pregnancy]. PMID- 1608521 TI - [Psychological adaptation to hysterectomy. Experience with 40 patients]. AB - To assess how hysterectomy was psychologically overcome we refer to the results obtained from a questionnaire given to 40 patients. The questionnaire was divided into 3 parts: one statistic-epidemiologic, one to evaluate the patients' level of information, and a third aimed at studying post-operative psychological and sexual adaptability. PMID- 1608522 TI - [LH-RH analogues in the preparation of hysteroscopic resection of uterine fibromyoma]. AB - Ten patients with submucous and/or intracavitary myomas, aged between 40 and 50 years old, underwent preliminary and preoperative (endoscopic resection) treatment with LH-RH. A using a depot formula. The Authors report the results of treatment efficacy (disappearance of symptoms and reduced myoma volume) in relation to an optimal surgical approach using an endoscopic route. This form of treatment allowed both operating times and intraoperative bleeding to be reduced. PMID- 1608524 TI - [Results of LHRH-A pretreatment in ovulation induction, using pulsatile administration of GnRH, in patients with polycystic ovaries]. AB - The use of GnRH pulsatile to induce ovulation is an efficacious and safe form of therapy in hypogonadotropic hypogonadism, whereas greater difficulties are encountered in the treatment of chronic anovulation due to PCOD. The paper reports the results of 12 ovulation induction cycles using a GnRH micropump without and after GnRH analogues. PMID- 1608523 TI - [Defibrotide vs. calcium heparin in the prevention of deep vein thrombosis in gynecologic oncologic surgery]. AB - Eighty-one patients were submitted to gynaecological malignancy surgery in a randomized study aimed at the evaluation of the efficacy of defibrotide (40 patients) and calcium heparin (41 patients) in perioperative prophylaxis. They were randomly allocated to defibrotide group (400 mg bid im starting one day before surgery and continuing until the 7th postoperative day) or calcium heparin group (5000 IU bid sc starting two hours before surgery and continuing likewise for 7 days). No cases of DVT diagnosed by means of a Doppler CW were observed in either treatment group. Laboratory parameters have shown similar modifications in the two treatment groups. Three cases of bleeding were observed in the calcium heparin group while no cases of bleeding were detected in the defibrotide group. The results obtained suggest that defibrotide is at least as effective as calcium heparin in perioperative DVT prevention and that the former drug has a possibly better tolerability profile, due to a decisively lower tendency to bleeding. PMID- 1608525 TI - [Efficacy of elastic compression stockings and administration of calcium heparin in the prevention of puerperal thromboembolic complications]. AB - Post-partum superficial and deep venous thrombosis are still an important obstetric problem. Varicose veins of the lower limbs are closely associated epidemiologically and pathogenically with venous thrombosis. A controlled group of 1,588 parturients was studied to single out other risk factors and to ascertain the prevalence of thrombosis. A group of 1,464 parturients was treated with graduated compression stockings, in low risk patients, adding preventive treatment with low dose heparin in high risk patients. The prevalence of post partum venous thrombosis was reduced from 4.3%, in the control group, to 0.9% in the study group: in women who received preventive treatment, the prevalence of thrombosis diseases was decreased over 90%. PMID- 1608526 TI - [Heterosexual transmission of HIV and a control organization model consisting of female subjects at the USL no. 36 Drug Control Service of Lugo]. AB - Human immunodeficiency virus-HIV heterosexual transmission is going to become the main problem in controlling the spread of HIV; our experience confirms the increased risk when genital lesions are present. These data advise to attend gynaecologic control of female drug addicts, often affected by sexually transmitted diseases, in order to realize primary and secondary HIV spreading prevention. PMID- 1608527 TI - [Incidence of beta-thalassemia heterozygotes among pregnant women in the High Madonie region]. AB - From January 1990 to July 1991 17 cases of beta-thalassemic heterozygotes were identified out of a population of 400 pregnant women born and living in the High Madonie area of Sicily (Alimena, Blufi, Bompietro, Castellana, Gangi, Geraci Siculo, Petralia Soprana and Sottana, Polizzi Generosa) with a frequency of 1 case out of 23.5 births (4.2%). PMID- 1608528 TI - [Uncomplicated pregnancy in patients with unrecognized primary biliary cirrhosis]. AB - A 32 yr-old woman suffering from an unsuspected primary biliary cirrhosis (PBC), completed an uneventual pregnancy. She only experienced diffuse pruritus and subicterus, which misled to an antepartum diagnosis of intrahepatic cholestasis of pregnancy. The most remarkable points of the reported case are: (a) the younger age of onset of PBC; (b) the paucisymptomatic course of PBC; (c) the rarity of PBC-associated pregnancy (only 15 previous instances in 12 patients, from a review of the literature); (d) the uncomplicated course of pregnancy for both the mother and the fetus, which is the exception rather than the rule, in such a condition. The present observation calls our attention to the possible existence of an underlying latent liver cirrhosis in pregnant women with pruritus, jaundice and mild alterations of liver function indexes. This association, which is expected to increase in frequency in the near future, may have important implications in the management of pregnancy. PMID- 1608529 TI - Short-term ethanol intoxication in rat. Effect on the entorhinal cortex. AB - The effect of short-term ethanol intoxication in systems implicated in memory and other cognitive functions in rats has been assessed by studying the variation in the karyometry of the neurons in the different layers of the lateral entorhinal cortex. The analysis showed that short-term ethanol consumption produced a reduction in the nuclear area of neurons in layers V and VI, and to a lesser extent, in layers II and III. These results suggest that the deep layers of the entorhinal cortex are more sensitive to ethanol intoxication, thus more likely affecting cortical and subcortical projections than the hippocampal output. PMID- 1608530 TI - The effects of morphine administered into the vertebral artery on the somatosympathetic A- and C-reflexes in anesthetized cats. AB - The effects of morphine (0.2-200 micrograms/kg) administered into the brain stem via a vertebral artery on the somatosympathetic A- and C-reflexes evoked in a cardiac sympathetic nerve by electrical stimulation of somatic myelinated (A) and unmyelinated (C) afferent nerve fibers in anesthetized cats were examined. The intravertebral arterial administration of 20-200 micrograms/kg morphine depressed dose-dependently both the somatosympathetic A- and C-reflexes. Following the administration of 200 micrograms/kg morphine, the amplitudes of the sympathetic A and C-reflexes were depressed to 71 +/- 8% and 80 +/- 8% of the control magnitude, respectively. Injection of 2-200 micrograms/kg morphine caused hypotension in a dose-dependent manner. It is concluded that morphine administered in the brain stem via the vertebral artery produced a nonselective and slight depression of both the somatosympathetic A- and C-reflexes by acting at the level of brain stem. PMID- 1608531 TI - Localization of gene expression of calbindin in the brain of adult rats. AB - Localization of gene expression of calbindin, a cytosolic calcium-binding protein, was examined throughout the adult rat brain by in situ hybridization with cDNA probes. The gene was expressed most intensely in the Purkinje cells in the cerebellum, intensely in the granule cells of the dentate gyrus, and moderately in the inferior olivary nucleus, in the nuclei of the trapezoid body, in the medial part of the lateral habenular nuclei, entorhinal cortex and in the mammillary nuclei. In addition, weak expression of the gene was widespread in the forebrain and brainstem gray matter, and also in small cells in the spinal posterior horn as well as the ependymal cells. The widespread and heterogeneous expression of the gene in the brain suggests that calbindin is differentially involved in calcium-regulated phenomena in different neurons. PMID- 1608532 TI - Synapse formation between dissociated basal forebrain neurones and hippocampal cells in culture. AB - Dissociated neurones from rat basal forebrain and hippocampus were co-cultured in vitro for 8-15 days. Patch-clamp recordings from individual presumed hippocampal pyramidal cells revealed synaptic currents following focal extracellular stimulation of single presumed basal forebrain neurones. Of 18 neurone pairs, 13 showed inward (excitatory) synaptic currents, 4 showed outward (inhibitory) synaptic currents, and 1 showed a mixed current. Latencies varied from 4 to 15 ms, suggesting both mono- and polysynaptic currents. These experiments indicate that synaptic connections can be established between basal forebrain and hippocampal cells in dissociated cell culture. PMID- 1608534 TI - Late onset and long-lasting suppressive effects of ceruletide, an analogue of cholecystokinin, on c-fos mRNA expression in the rat striatum. AB - C-fos mRNA expression by stimulation with subcutaneous (s.c.) administration of saline or cycloheximide (CHX) was examined in the rat striatum with or without pretreatment with ceruletide, an analogue of cholecystokinin. The c-fos mRNA induction 1 h after CHX stimulation (25 mg/kg, s.c.) was significantly suppressed by ceruletide pretreatment (80 micrograms/kg, s.c.) 2 h before CHX stimulation in the striatum, and tended to be suppressed by ceruletide pretreatment 4 h before saline or CHX stimulation. Long-lasting and inhibitory effects of ceruletide on dyskinesia and on dopaminergic (DAergic) neuronal systems, and c-fos mRNA expression by activation of the DAergic system have been reported. The present findings together with previous reports suggest that ceruletide might have late onset and long-lasting suppressive effects on the expression of c-fos mRNA in the striatum and that these effects might be related to its effects on DAergic neuronal transmission. PMID- 1608533 TI - Characterization of Alzheimer amyloid precursor protein transcripts in platelets and megakarocytes. AB - Immunoblot analyses indicate that the platelet is a reservoir of several Alzheimer amyloid precursor protein (APP) isoforms, including C-terminal reactive species which could potentially serve as the precursor of the amyloid beta protein (AB*) in Alzheimer's disease (AD). Since platelets are known to sequester several plasma proteins from the blood, we employed the polymerase chain reaction (PCR) to amplify reverse transcribed mRNA and detect the 3 major APP transcripts (APP695,751,770) in platelets and the Dami megakaryocyte cell line. PCR amplification of glycoprotein IIb and HLA-DR mRNA was used to demonstrate that APP transcripts were derived from cells of megakaryocytic lineage, and the results were compared with those obtained from peripheral blood mononuclear cells, human umbilical vein endothelial cells, B lymphocyte and astrocytoma cell lines. The identity of PCR products was confirmed by hybridization with APP specific oligonucleotide probes, and sequencing of amplified segments. PMID- 1608535 TI - Immunocytochemical localization of synaptic vesicle-specific protein in Lewy body containing neurons in Parkinson's disease. AB - We carried out an immunocytochemical examination of the brainstem and sympathetic ganglia of 5 autopsied patients with Parkinson's disease, using monoclonal antibodies against microtubule-associated protein 2 (MAP2) and synaptic vesicle specific 38 kDa protein (SVP38). Lewy bodies (LBs) in the nerve cell somata were often immunoreactive for MAP2. Immunoreactivity of SVP38 in the somata of nerve cells was rarely demonstrated in the peripheral portion of the LBs. On the other hand, SVP38-immunoreactive (IR) LB-containing nerve cell processes were frequently found in the brainstem and sympathetic ganglia, considerably outnumbering MAP2-IR LB-containing nerve cell processes. These findings suggested that SVP38 is stored in LB-containing nerve cell processes and indicate that the majority of these processes are axons. PMID- 1608537 TI - Neuropeptide Y does not alter NMDA conductances in CA3 pyramidal neurons: a slice patch study. AB - Neuropeptide Y (NPY) has been reported to inhibit excitatory neurotransmission in hippocampus presynaptically. Recently, it has been suggested that NPY also potentiates N-methyl-D-aspartate (NMDA)-mediated excitatory responses in hippocampus, by action at a sigma or phencyclidine (PCP) binding site. We tested this hypothesis by examining the action of NPY on CA3 pyramidal cells using slice patch voltage clamp recordings. NPY did not affect inward currents elicited by iontophoresis of NMDA onto the proximal dendrites of these cells under two different conditions, but did reduce the excitatory postsynaptic currents elicited by mossy fiber stimulation. NPY therefore does not appear to directly alter the postsynaptic NMDA response in CA3 cells. PMID- 1608536 TI - Immunoreactive corticotropin-releasing hormone levels in the hypothalamus of female Wistar fatty rats. AB - We have studied immunoreactive corticotropin-releasing hormone (CRH) levels in the hypothalamus of female Wistar fatty rats, a strain with the fa gene transferred from the Zucker rat to the Wistar Kyoto rat, in an attempt to understand the role of CRH in the development of obesity. A study was conducted with 5-week- and 12-week-old female Wistar fatty rats and lean littermates. There was no significant difference in hypothalamic CRH levels between lean and obese rats at the age of 5 weeks (1887 +/- 99.6 vs. 1767 +/- 124 pg/tissue; mean +/- S.E.M.). Hypothalamic CRH immunoreactivities, however, were significantly lower in 12-week-old obese rats (2361 +/- 132 pg/tissue) than those in lean littermates (2992 +/- 118 pg/tissue; P less than 0.05). The difference of CRH contents between the lean and obese group becomes apparent as they grow up and develop obesity. PMID- 1608538 TI - Epidermal growth factor induces glucose transport in primary cell cultures derived from human astrocytic glioma biopsies. AB - The gene for the epidermal growth factor (EGF) receptor is amplified in a variety of neoplastic tissues, including malignant gliomas. To reveal whether increased sensitivity to EGF has significance for the supply of metabolic substrate to tumor cells, the rate of glucose transport was determined in cells exposed to EGF for up to six hours. In the epidermoid carcinoma line A431, and in primary cultures from 7/12 human glioma biopsies, EGF (10 ng/ml) induced an increase (two fold) in glucose transport. This effect was transient and independent of protein synthesis. PMID- 1608539 TI - Detection of free radicals during brain ischemia and reperfusion by spin trapping and microdialysis. AB - Extracellular free radicals were detected in rat striatal perfusate samples by intracerebral microdialysis coupled to the spin trapping technique. Five Sprague Dawley rats were subjected to 30 min of global ischemia followed by reperfusion; throughout the experimental period the intrastriatal dialysing probe was perfused with Ringer's solution containing the spin trap agent pyridyl-N-oxide-t butylnitrone (100 mM) together with the iron chelating agent diethylentriaminepentacetic acid (100 microM). A radical adduct occurred during ischemia and early reperfusion, but not in basal conditions; the spin adduct was characterized as a carbon centered radical, consistent with the presence of an oxidative attack on membrane lipids. The direct evidence of the formation of free radicals supports the hypothesis that free radicals play a role in the pathogenesis of the histological damage during brain ischemia. PMID- 1608540 TI - Peroxisomal enzyme activities in brain and liver of pups of lactating mothers treated with ciprofibrate. AB - Peroxisomal activities were examined in liver and brain of lactating neonatal rats of mothers maintained on ciprofibrate, a peroxisomal proliferator. The activities of DHAP-acyltransferase, alkyl-DHAP synthetase and the beta-oxidation of palmitic and lignoceric acids increased in brain by 3.9, 2.2, 4.3 and 3.2 fold and in liver by 3.2, 2.6, 6.2 and 2.5 fold, respectively, of lactating pups from mothers on ciprofibrate diet as compared to controls. Ciprofibrate treatment increased the peroxisomal enzyme activities in both brain and liver of lactating neonatal rats demonstrating that ciprofibrate or its metabolite(s) transmitted through the mother's milk can effectively induce peroxisomal proliferation. PMID- 1608541 TI - Gene expression of apolipoprotein E in human brain tumors. AB - Samples of normal brain, two meningiomas, one medulloblastoma and seven astrocytomas were analyzed along with two glioma lines to determine the genic expression of apolipoprotein E, which in addition to its major function in lipid metabolism has been postulated to be a marker for astrocytomas. Messenger ribonucleic acid encoding apolipoprotein E was found to be expressed in significant amounts in all of the brain tumor specimens and in the normal brain, but in only one of the two glioma lines. Although the role of apolipoprotein-E in the brain and in brain tumor growth remains undefined, it is clear that this gene is expressed in substantial amounts in a variety of brain tumors and is not specific for astrocytomas. PMID- 1608542 TI - Anatomical evidence for segregated input from the upper cervical spinal cord to functionally distinct regions of the periaqueductal gray region of the cat. AB - In the cat, the caudal third of the midbrain periaqueductal gray region (PAG) mediates two distinct behavioral and cardiovascular patterns: (i) flight and hypertension from the lateral PAG and (ii) immobility and hypotension from the ventrolateral PAG. The afferent input from the upper cervical spinal cord (UCC) to these functionally distinct PAG regions was investigated using retrograde tracing techniques. The following results were obtained: (i) following tracer injections into the lateral PAG large numbers of labelled cells were found in lamina I and the lateral cervical nucleus; (ii) following tracer injections into the ventrolateral PAG large numbers of labelled cells were found in the ventral horn; (iii) both PAG regions received substantial projections from UCC cells in laminae IV and V, however, no double labelled cells were observed. Thus, functionally distinct regions of the caudal PAG are targeted by quite separate and discrete UCC neural populations. These anatomical differences likely reflect functionally distinct UCC afferent regulation of the functionally opposite PAG regions. PMID- 1608543 TI - The lateroposterior thalamic nucleus and substantia nigra pars lateralis: origin of dual innervation over the visual system and basal ganglia. AB - Employing the fluorescent retrograde double labeling technique, the present study demonstrated that in the rat single neurons in the lateroposterior thalamic nucleus (LP) project to both the visual cortex and striatum, and that single neurons in the substantia nigra pars lateralis project to both the LP and striatum, or to both the superior colliculus and striatum. These results provide morphological evidence for the functional correlation between the visual system and basal ganglia. PMID- 1608544 TI - Human Schwann cells in culture: characterization and reactivity with human anti sulfated glucuronyl glycolipid monoclonal IgM antibodies. AB - Schwann cells in cultures derived from human fetal peripheral nervous system were characterized by their morphology and indirect immunofluorescence with anti galactocerebroside and anti-laminin antibodies. They stained strongly with human monoclonal IgM anti-sulfated glucuronyl glycolipid antibodies in double labeling experiments. PMID- 1608545 TI - The contribution of epinephrine to experimentally induced urethral inflammation in the rat. AB - We have studied the effect of the adrenal medulla and epinephrine on experimentally induced urethral inflammation in the rat. Urethral inflammation was induced by inserting latex strips into the urethra. The effects of different experimental procedures were assessed by using a 4-graded inflammation scale based on histological findings. Adrenal medullectomy significantly reduced experimentally induced urethral inflammation. This effect was reversed if the rats were treated repeatedly with epinephrine or salbutamol. On the other hand high doses of epinephrine reduced the experimentally induced urethral inflammation. PMID- 1608546 TI - Firing behaviour of anticompensatory neurones in the prepositus hypoglossi nucleus of alert cat. AB - The present results demonstrate that anticompensatory neurones could be recorded within the prepositus hypoglossi nucleus of the alert cat. These neurones, like burster-driving neurones described in paralysed cats, were characterized by a tonic increase of firing for head turning in the contraversive direction (type II) associated to bursts for each vestibular quick phase in the same direction. They were also involved in the generation of visually triggered saccades since they displayed a burst preceding contraversive saccades and a pause in the opposite direction. Thus, these neurones code eye velocity for both vestibular quick phases and visually triggered saccades in addition to head velocity. Such a firing behaviour suggests that, in addition to the classical crossed tecto reticulo-spinal network, an ipsilateral pathway could also be involved in the generation of visually triggered rapid eye movements. PMID- 1608547 TI - Ethanolamine is released from glial cells in primary culture on stimulation with foetal calf serum and phorbol ester. AB - Ethanolamine is released to the external medium at increased rates over basal levels when [3H]ethanolamine-labelled glial cells in primary culture, subcultures of astrocytes and O-2A lineage glia or C6 glioma cells are treated with phorbol ester or foetal calf serum. On equilibrium labelling of mixed glial cultures 90 95% of incorporated [3H]ethanolamine was in ethanolamine-containing phospholipids and 2% in the phosphatidylcholine component. On stimulation of glia with phorbol ester or foetal calf serum ethanolamine, and not phosphoethanolamine or choline, was released to the medium suggesting that a phospholipase D-mediated turnover of lipid, perhaps partially linked to protein kinase C, is involved. The results show that cells in primary culture behave similarly to cell lines in that signal transduction pathways involve a stimulated turnover of ethanolamine-phospholipids with the external release of ethanolamine. PMID- 1608548 TI - Norepinephrine-induced increase in sympathetic neuron-derived prostaglandins is independent of neuronal release mechanisms. AB - The contribution of exocytosis to norepinephrine-stimulated prostaglandin release from sympathetic postganglionic neurons was evaluated in homogenates of adult rat superior cervical ganglia. Incubation of ganglion homogenates with norepinephrine (1 mM) for 30 min caused an increased release of prostaglandin E2 and prostaglandin I2 (measured as the stable metabolite, 6-keto-PGF1a). Neither tetrodotoxin (10 mM), K+ (120 mM), nor EDTA in Ca(2+)-free buffer affected prostaglandin generation under basal and norepinephrine-stimulated conditions. These results suggest that the increase in prostaglandin production by sympathetic neurons after norepinephrine administration is not through the release of previously synthesized intracellular stores. Instead, the increase in prostaglandins in response to norepinephrine appears to be explained by de novo synthesis. PMID- 1608549 TI - Direct activation of purified Go-type GTP binding protein by tricyclic antidepressants. AB - A growing body of evidence suggests that tricyclic antidepressant agents (TCAs) interact with GTP binding proteins (G proteins). We have investigated if TCAs directly alter the function of the purified Go protein which is specifically expressed in neuronal tissue. Several TCAs markedly enhanced the GTPase activity of Go protein in a pertussis toxin-susceptible manner, whereas MAO-inhibitor and anxiolytic agent did not. This enhancing effect of TCAs on Go function may be due to an increase in the GDP-GTP exchange reaction occurring on Go. Thus, it is very likely that TCAs can modify various signal transduction by directly interacting with G proteins in brain cells. PMID- 1608550 TI - Nitric oxide (NO) is involved in increased cerebral cortical blood flow following stimulation of the nucleus basalis of Meynert in anesthetized rats. AB - The effects of i.v. administration of a nitric oxide (NO) synthase inhibitor, L NG-nitroarginine (L-NOArg), on the increase in cerebral cortical blood flow (cortical BF), following either electrical stimulation of the nucleus basalis of Meynert (NBM), whose cholinergic fibers project to the cortex, or hypercapnia with 10% CO2 inhalation, were studied in anesthetized rats. Cortical BF was measured using laser Doppler flowmetry. The threshold intensity of electrical stimulation of the NBM (0.5 ms, 50 Hz for 10 s) that induced an increase in regional cortical BF was defined as 1T. The cortical BF was increased on a stimulus intensity dependent manner at 1T-5T intensities tested. L-NOArg was administered cumulatively i.v. starting from 0.3 mg/kg, then 3 mg/kg, and 30 mg/kg. Time interval between each cumulative administration of L-NOArg was approximately 40 min. Three and 30 mg/kg of L-NOArg significant reduced the NBM stimulation-induced increase of cortical BF at intensities of 2T and 3T. The response at an intensity of 5T was reduced only by 30 mg/kg of L-NOArg to about half the control response. The reduced responses at 2T, 3T, and 5T were reversed following the i.v. administration of a physiological precursor of NO, L-arg (300 mg/kg). Inhalation of 10% CO2 for 15 s induced an increase in cortical BF which was not influenced by L-NOArg and L-Arg. These results suggest that NO is a necessary factor in the vasodilation of the cortical BF that is brought about by cholinergic fibers originating in the NBM. PMID- 1608551 TI - Neuropeptide content of purified rat brain cholinergic synaptosome subpopulations. AB - Cholinergic synaptosomes from rat cerebral cortex were isolated by a magnetic immunoaffinity technique, i.e. immunomagnetophoresis. This subpopulation was extracted and subjected to radioimmunoassay for 4 neuropeptides:neuropeptide Y (NPY); vasoactive intestinal peptide (VIP); substance P (SP); and somatostatin (SRIF). Three of the 4 neuropeptides were enriched in the sorted fraction compared with the mother fraction with respect to the cytosolic marker lactate dehydrogenase (LDH). The most enriched neuropeptide was NPY followed by SP and VIP. Somatostatin was not enriched in the cholinergic synaptosome subpopulation. The presence of NPY has not previously been reported in cortical cholinergic neurones. PMID- 1608552 TI - Mesencephalic trigeminal nucleus neurons with collaterals to both the masseter and the inferior alveolar nerves. A fluorescent double-labeling study in the rat. AB - After fluorescent tracers were applied to the inferior alveolar nerve and the masseter nerve on the same side of the rat, double-labeled neurons were observed in the caudal part of the mesencephalic trigeminal nucleus (Vme), reflecting simultaneous innervation of both the periodontal ligaments and masseter muscle spindles by collaterals of peripheral processes of single Vme neurons. PMID- 1608553 TI - Restructuring of sleep and reversal of REM-induced supraspinal hypotonia of respiratory muscles following bilateral phrenicotomy. AB - The long-term effect of diaphragm paralysis on respiratory system function is still not clear. We monitored changes in breathing pattern and the sleep/wake cycle in a dog before and after bilateral phrenicotomy. The post-operative observation extended over 6 months. It was noted that minute ventilation increased during wakefulness and non-REM sleep in the initial 4-6 weeks (compared to pre-surgery period), but decreased during REM sleep, mainly due to inhibition of chest wall and abdominal muscles. These episodes resulted in hypoxemia and frequent arousals. Following this period, there was a restructuring of REM sleep, increasing the frequency of REM sleep and reducing the duration of each REM sleep episode. In addition, the enhanced activity of parasternal and abdominal muscles was persistently seen during REM sleep. These changes in breathing and sleep provided stable ventilation during sleep. We conclude that bilateral phrenicotomy restructures breathing and alters sleep/wake cycle to prevent nocturnal hypoxemia. The mechanisms underlying these changes may reflect plasticity in the control of breathing and REM sleep. PMID- 1608554 TI - Serotonergic excitatory drive to hypoglossal motoneurons in the decerebrate cat. AB - In decerebrate, paralyzed, vagotomized and artificially ventilated cats, serotonin (5-HT) and its analogues, microinjected into the hypoglossal (XII) motor nucleus, altered the activity of the genioglossal branch of XII nerve. 5 HT, carboxamidotryptamine maleate (5-CT) and DOI (1-5 mM) increased the activity by over 200%. Methysergide reversed this increase. Methysergide, mianserin, or ketanserin (100-250 nl, 1 mM) reduced the spontaneous hypoglossal activity by 20 50%. Buspirone, 8-OH-DPAT and (-)-propranolol were without effect. Thus, 5-HT provides a substantial tonic excitatory drive to XII motoneurons. The 5-HT receptors involved are likely to be type 1C or 2, but uncertainty regarding the affinity profiles of the drugs used in in vivo conditions in the cat precludes a definite identification. PMID- 1608555 TI - Retinoic acid affects the organization of reticulospinal neurons in developing Xenopus. AB - The effects of all-trans retinoic acid (RA) on the differentiation of the reticulospinal system were studied in Xenopus. RA was applied in concentrations of 10(-5) and 10(-6) M for 30 min at stage 12. When siblings had reached stages 46-48, the spinal cord was transected in anesthetized control and experimental animals and the reticulospinal cells were visualized through retrograde transport of fluorescing dextran amines. The lower concentration of RA led in many animals (22%) to the formation of multiple Mauthner-like cells. Higher concentrations resulted in the formation of two uninterrupted longitudinal columns of rather uniform reticulospinal cells. These data suggest that the normal expression of Hox genes pattern--known to be altered by RA--may be necessary for the differential specification of compartments of the reticulospinal system. PMID- 1608556 TI - Seasonal changes in the suprachiasmatic nucleus of man. AB - The mammalian suprachiasmatic nucleus (SCN) is considered to be the principal component of the biological clock, generating a wide variety of physiological and behavioral circadian rhythms. In addition to its implication in circadian rhythms, the SCN is also involved in the expression of some seasonal cycles. In the present study we show that the volume of the human SCN and the number of vasopressin-immunoreactive neurons contained within it fluctuate significantly over the year, with values being about twice as high in the autumn as in the summer. In contrast, no seasonal variations could be detected in the paraventricular nucleus (PVN), another major vasopressinergic cell group in the hypothalamus. The present findings suggest that the human SCN is influenced by seasonal variations in photoperiod. PMID- 1608557 TI - NADPH diaphorase-positive neurons in the rat spinal cord include a subpopulation of autonomic preganglionic neurons. AB - Preganglionic neurons in the spinal cord of the rat were labelled retrogradely with Fluoro-gold and the spinal cord stained for NADPH diaphorase. The majority of both sympathetic and sacral parasympathetic preganglionic neurons showed staining for NADPH diaphorase. NADPH diaphorase-positive neurons were located more laterally in the intermediate zone than were preganglionic neurons lacking NADPH diaphorase staining. The recent evidence that identifies NADPH diaphorase as nitric oxide synthase raises the possibility that some spinal preganglionic neurons may synthesize nitric oxide. PMID- 1608558 TI - Differences in the temperature dependencies of uptake of botulinum and tetanus toxins in Aplysia neurons. AB - The respective neuroselective actions of botulinum type A (BoNT) and tetanus (TeTx) neurotoxins on cholinergic and non-cholinergic synapses of Aplysia are mainly due to differences in their extracellular neuronal targetting. Further information was gained on this neuroselectivity by examining the temperature dependencies of binding, internalization and intracellular action of both toxins. After reduction of temperature from 22 degrees C to 10 degrees C, the binding of neither BoNT nor TeTx was significantly altered whereas the neuronal uptake of BoNT, but not of TeTx, was prevented. Although TeTx internalization could be detected at the low temperature, its intracellular activity was greatly attenuated compared to that of BoNT. It is inferred that the uptake mechanisms are different for these two related but distinct toxins. PMID- 1608559 TI - Fat as fuel and metabolic signal. PMID- 1608560 TI - Sensory properties of fats and fat replacements. PMID- 1608561 TI - Essential fatty acids: the importance of n-3 fatty acids in the retina and brain. PMID- 1608562 TI - The role of dietary fatty acids in biology: their place in the evolution of the human brain. PMID- 1608563 TI - Dietary fat and blood lipids. PMID- 1608564 TI - Marine oils and their effects. PMID- 1608565 TI - Isomeric fatty acids and serum lipoproteins. PMID- 1608566 TI - Dietary fats: long-term implications for health. PMID- 1608567 TI - Oncology nurse practitioner provides continuity of care. PMID- 1608568 TI - Assessment and treatment strategies for depressive disorders commonly encountered in primary care settings. AB - Frequently overlooked, depression is a very common complex disorder that causes significant morbidity and mortality. This article provides a review of three commonly encountered depressive disorders in primary care settings: adjustment disorder with depressed mood, dysthymia and major depression. Since many individuals minimize the affective symptoms of depression, clinicians must maintain a high index of suspicion when clients present with vague somatic complaints, such as fatigue, headache, constipation and difficulty sleeping. To reach an accurate diagnosis, a thorough history, physical examination and appropriate laboratory studies should be performed. Numerous rating scales are presented to aid assessment. Common intervention strategies for the treatment of depressive disorders include education, drug therapy, and supportive individual and family counseling. PMID- 1608569 TI - Guidelines for rapid assessment of abdominal pain indicative of acute surgical abdomen. AB - Abdominal pain is one of the most frequently described reasons for ambulatory visits. The complaint of abdominal pain requires an orderly and thorough approach because even mild or non-specific pain can denote a potentially life-threatening intra-abdominal pathology. The majority of patients with acute abdomen can be diagnosed by a direct and concise history, and a thorough physical examination supplemented by simple laboratory and radiologic testing. This article includes key history, physical and clinical indicators that should suggest to the clinician the need for immediate surgical intervention. When an acute abdomen is suspected, the goal of patient management is to rapidly and accurately diagnose the patient preoperatively, and to provide a timely referral to the appropriate surgeon or gynecologist. PMID- 1608570 TI - Consensus among geriatric experts on the components of a complete nursing-home admission assessment. AB - Standards of practice for nursing-home admissions have not been established, and it is not known if geriatric clinicians agree on the components of an appropriate patient-admission evaluation. This study describes the consensus expressed by experts in clinical geriatrics regarding the most important components of nursing home admission assessments. Directors of all geriatric-nurse-practitioner and geriatric-medicine fellowship programs (n = 79) were sent a two-round questionnaire asking them to describe and rate the components of a "complete admission assessment for every elderly patient entering a nursing home." Nurse practitioners and physicians ranked medication review, evaluation of urinary incontinence, mental status, vision and bowel status the highest, and gave them equal priority. Routine laboratory tests were not included among the highest ranked items by either nurses or doctors. An enhanced assessment focusing on the functional consequences of diseases rather than on the traditional "head-to-toe" systems approach emerged as the most appropriate assessment for elderly nursing home patients. PMID- 1608572 TI - Tips for obtaining recertification. PMID- 1608571 TI - Prevention and primary care treatment of stings from imported fire ants. AB - Stings from imported fire ants constitute a problem encountered more and more frequently in practice settings across the Southern United States. Envenomation (impregnation of venom) in children is especially common. Current medical regimens for the treatment of other stinging insects are of little value in preventing local cutaneous reactions to fire-ant stings. The pathogenesis of reactions from imported-fire-ant stings is discussed, and suggestions for prevention, treatment and patient education are provided. PMID- 1608573 TI - Nurses must ensure that women make informed decisions about abortion. PMID- 1608574 TI - Good ideas for enrolled nurses. PMID- 1608575 TI - Contract blues? NZNA can help you! PMID- 1608576 TI - Think about it! PMID- 1608577 TI - Professional ignorance towards addiction. PMID- 1608578 TI - How can nurses measure their worth? PMID- 1608579 TI - Why stop at the hospital. PMID- 1608580 TI - Interrelations in nursing. Part II. PMID- 1608581 TI - Sexual harassment at work: the role of the OHN. PMID- 1608582 TI - Planning for workplace emergencies. PMID- 1608583 TI - Cancer. Learning to cope. PMID- 1608584 TI - Noise--preserving 'inches of tick'. PMID- 1608585 TI - Clinical waste--disposal awareness. PMID- 1608586 TI - Metal ion catalyzed liquefaction of vitreous by ascorbic acid: role of radicals and radical ions. AB - The effect of Fe2+ and Cu2+ on the intact calf vitreous in the presence or absence of exogenous ascorbic acid was investigated in vitro. Liquefaction of vitreous gel was evident in the presence of either ion. The loss of gel structure was greater in the presence of exogenous ascorbic acid than in its absence. As shown by high-performance liquid chromatography, liquefaction was accompanied by depolymerization of vitreous hyaluronic acid which is degraded by .OH, generated by the metal ion catalyzed oxidation-reduction system. The involvement of .OH in this process was also evident from the significant reduction in liquefaction in the presence of the .OH-specific scavenger mannitol. PMID- 1608587 TI - Optimal pupil diameter for Scheimpflug slit image photography of the lens in man. AB - Densitometric analysis of Scheimpflug photography of the lens has been examined as a function of pupil diameter in normal volunteers. On the basis of both the length of the lens waveform and the integral area under the curve of the lens waveform, there is a critical pupil diameter above which the waveform is unchanged. Below this critical diameter the waveform becomes distorted by shortening and a change in shape. The critical pupil diameter is between 6 and 6.5 mm. This result is of importance either in longitudinal studies, where the pupil diameter may not be reproducible, or in studies where other drugs are used which may prevent full pupil dilatation. PMID- 1608588 TI - Infiltrating lymphocytes and antigen expression in uveal melanoma. AB - Monoclonal antibodies and flow cytometry were used to study lymphocyte, monocyte and tumor cell antigen expression in uveal melanoma. Forty-one melanomas were studied after various forms of treatment. An antimelanoma antibody, 13A3E, stained 81.7% of the cells. Tumors treated with helium ions or 125I plaques had 13A3E staining reduced to 62.5%, p = 0.011. HLA-A,B,C stained 85.4%, and HLA-DR stained 7.0% of the cells. T cells (CD3 positive) comprised 4.5% (range 0.1 29.2%) of total cell population. Natural killer (NK) cells, B cells and macrophages were present in small numbers (mean less than 2.5% in each case). Tumors with numerous T cells (greater than 5%), were used for T cell subtype studies. The mean helper/inducer (CD4) to cytotoxic/suppressor (CD8) ratio was 1.00 (range 0.11-3.15). CD8 decreased, and CD4 increased with age in unirradiated tumors (p less than 0.02). PMID- 1608589 TI - Biometric constancy of the anterior eye segment as demonstrated by slit image photography according to the Scheimpflug principle. AB - According to the accommodation changes in the lens described by Brown, the distance from the cornea vertex was determined in 192 Scheimpflug photos with the aid of a line drawn through the equator of the lens nucleus. The mean value for this section of the total distance was 5.75 mm, the variations being within the range of 5.38-5.9 mm. These results are of importance in the development of refraction and emmetropization of the eye as well as for the determination of the postoperative anterior chamber depth in cataract surgery and a criterion for the different types of glaucoma. PMID- 1608590 TI - Distribution and kinetics of the inflammatory cell response to ocular challenge with Pseudomonas aeruginosa in susceptible versus resistant mice. AB - This study examined and characterized the distribution and kinetics of the inflammatory cell response to pseudomonas ocular challenge in susceptible C57BL/6J and resistant DBA/2J mice. Initially, in the cornea, the number of neutrophilic leukocytes (PMNs), macrophages/monocytes or lymphocytes was 2-2.5 times greater in resistant versus susceptible mice. The peak cellular response in the cornea was also greater in resistant than in susceptible animals. Further, resistant mice, when compared with susceptible mice, had a shorter duration of inflammatory cells as well as bacteria in the cornea. These data were similar for the cell infiltrate in the anterior chamber, with the exception that PMNs were initially greater in number in C57BL/6J than in DBA/2J mice. Collectively these data suggest that susceptible mice are, in general, cellularly hyporesponsive to pseudomonas ocular challenge when compared with resistant animals. This, together with persistence of inflammatory cells and bacteria in the cornea of susceptible animals, may contribute to their failure to restore corneal clarity following pseudomonas ocular challenge. PMID- 1608591 TI - Organization of capillaries in the primate conjunctiva. AB - Conjunctival capillaries in the monkey were observed in histological sections to organize approximately parallel and close to the basement membrane of the epithelium, while larger vessels including the lymphatics were disposed deeper in the stroma. This peculiar vascular organization was evident in the palpebral but not in the bulbar conjunctiva. The trilaminar relationship that existed between the conjunctival epithelium, the elastic lamina previously described [1] and the capillaries is discussed. It was argued that such subepithelial capillary organization enhances the exchange of nutrients and gases between the cornea and the conjunctival vessels across the palpebral conjunctival epithelium when the lids are shut during sleep. PMID- 1608592 TI - Scanning electron microscopic and energy-dispersive X-ray analysis findings on two brand new intraocular lenses. AB - Two intraocular lenses (IOLs) from the same manufacturer showed surface particles by scanning electron microscopy. With energy-dispersive X-ray analysis, these were shown to contain Mg-Si, Al-Mg-Si, Ti, Fe, Ca and Cu. A sterile chronic intraocular inflammation may result from implantation of such contaminated IOLs. PMID- 1608593 TI - Immunohistochemical characterization of experimental Greene melanoma. AB - 20 experimental amelanotic Greene melanomas implanted into the anterior chamber of rabbit eyes were examined immunohistochemically in paraffin sections. All the Greene melanomas were found to be positive for vimentin, S-100 and HMB 45 and negative for alpha-human chorionic gonadotropin, neuron-specific enolase, chromogranin, synaptophysin, cytokeratin, carcino-embryonic antigen, serotonin, desmin and pan leukocyte marker T-200. Greene melanoma is comparable with human cutaneous and uveal melanoma in its immunohistochemical reaction pattern. PMID- 1608594 TI - Hydration and elevated calcium alone do not produce xylose nuclear cataract: role of proteolysis by calpain. AB - The purpose of this experiment was to determine the contribution of calpain proteolytic enzyme (EC 3.4.22.17) in the formation of nuclear cataract during lens culture in xylose. Increased lens calcium was found to be required for formation of xylose nuclear cataract in our culture system. Inhibition of calpain by the cysteine protease inhibitor E64 was effective in slowing the formation of nuclear cataract, even though lens calcium and hydration were markedly elevated. These results showed that hydration and elevated calcium alone do not produce xylose nuclear cataract, and they indicated that calpain proteolysis may be necessary for xylose nuclear cataract in the rat lens. PMID- 1608595 TI - Ultrastructural study of the retina in late infantile metachromatic leukodystrophy. AB - The autopsy of a 2-year-old girl revealed a clinically unrecognized metachromatic leukodystrophy (MLD) due to an aryl-sulfatase A deficiency, characteristically affecting the central and peripheral nervous system by demyelination and by accumulation of metachromatic material. The retina though reported clinically as normal, showed the same demyelinating process in the optic nerve including the papilla but an additional intraneuronal storage of MLD-typical lysosomal residual bodies in ganglion cell perikarya of the retina. Cells of the bipolar and photoreceptor layers as well as pigment epithelial cells were not affected by MLD specific lysosomal storage. Thus, sulfatides seem to play a particular metabolic role in ganglion cells but not in other neuronal cells of the retina in MLD. PMID- 1608596 TI - Effect of stimulus contrast on simultaneous steady-state pattern reversal electroretinogram and visual evoked response. AB - We studied the effect of stimulus pattern contrast on the simultaneously recorded pattern reversal electroretinogram (PERG) and pattern reversal visual evoked response (PVER) at 5 check sizes. The stimulus contrast ranged from 24 to 95% in 6 steps of 0.1- or 0.15-log unit increments. PERG amplitude showed a linear increase with an increase in pattern contrast at all check sizes. PVER amplitude showed an increase up to a certain pattern contrast, but was saturated upon further increase in stimulus contrast at all check sizes. The PERG amplitude check size function curve showed a flattened, inverted-U shape only with the highest contrast and low-pass filter shape or flat shape with lower contrasts. The PVER amplitude-check size function curve showed an inverted-U shape (bandpass filter shape) at all contrasts. These characteristics to the changes in contrast and the spatial frequency tuning suggest that PVER is processed in a different location of visual pathway than PERG. PMID- 1608597 TI - Hamster Greene melanoma implanted in the anterior chamber of a rabbit eye: a reliable tumor model? AB - The hamster Greene melanoma (HGM), implanted into the anterior chamber (AC) of a rabbit eye, has previously been used as a model for testing experimental therapies against human uveal melanomas. Even without therapy, the tumor showed necrosis and hemorrhages 8-10 days after inoculation. These changes could interfere with the interpretation of the results of experimental therapies. In 8 rabbits, a piece of HGM was implanted subcutaneously, and after 4 weeks, HGM was also implanted in the AC of the eye. In these eyes, tumor growth in the AC slowed down, and more necrosis and hemorrhages were found clinically and histologically as compared to 8 rabbits without previous subcutaneous implantation of HGM. In spite of the long use of this tumor and frequent transfer, the tumor cells did not lose their antigenic potential. PMID- 1608598 TI - Intraocular irrigating solutions and vitrectomy-related changes (in protein, lactic and ascorbic acid) in rabbit vitreous. AB - Vitrectomy and the subsequent vitreous fluid exchange alter the chemical and physical properties of the vitreous. This study assessed the time course alterations of total protein, ascorbic acid and lactic acid in the rabbit vitreous cavity following vitrectomy. Normal values were 2.2 +/- 1.2 mg/ml, 8.5 +/- 1.0 mg/100 ml and 16.8 +/- 3.5 mumol/ml, respectively. Nine groups of 5-10 adult albino rabbits underwent closed vitrectomy using physiologic saline, Ringer's lactate and BSS plus solutions. Samples were withdrawn at 3 and 24 h and 7 days after vitrectomy. Total protein levels increased in all groups at 3 and 24 h (20-30 mg/ml). Ascorbic acid measurements at 24 h rose only with saline and BSS plus. At 24 h the BSS plus group was the only one demonstrating an increased lactic acid concentration. PMID- 1608599 TI - L-ascorbic acid 2-phosphate enhances the production of type I and type III collagen peptides in cultured rabbit keratocytes. AB - We studied the effect of L-ascorbic acid 2-phosphate (P-Asc), a long-acting phosphate derivative of L-ascorbic acid, on the production and secretion of type I and type III collagen peptides in cultured rabbit keratocytes using immunohistochemistry and enzyme immunoassay. P-Asc enhanced production and secretion of these collagen peptides. Our observations support a therapeutic role for P-Asc in the repair of corneal stromal damage such as caused by corneal chemical burn. PMID- 1608600 TI - Enzymatic distribution patterns of rat lenses and the changes that occur during naphthalene cataract development. AB - The topographic distribution of enzyme activities in normal rat lenses and their changes occurring during naphthalene cataract development were investigated. Cataract formation was documented by slit images according to the Scheimpflug principle. Before the onset of visible changes and after the development of early visible opacities, the animals were sacrificed, their lenses removed and biochemically analyzed. The lenses were divided reproducibly into 6 parts--the equatorial ring and 5 layers of central cylinders from the anterior to the posterior cortex. The enzyme activity spectra (AR, SDH, GR, GPX, PFK, ALD, GAP DH, and LDH) showed region-related patterns, which could not be detected with analysis of the total lens. Image analysis of the first signs of opacity showed that changes in the activities of several enzymes correlate with density changes in the corresponding lens layers. PMID- 1608602 TI - Tear potassium contributes to maintenance of corneal thickness. AB - Isolated rabbit corneas were bathed on their endothelial surfaces with normal Krebs bicarbonate Ringer solution, while the epithelial surfaces were bathed in a basic tear solution containing sodium and potassium. When bathed in basic tear solution alone, corneal swelling occurred at an average of 12 microns/h over a 3 hour period. Corneal swelling occurred at a rate of about 21 microns/h when the epithelial solution was switched from normal basic tear solution to an iso osmotic K(+)-free basic tear solution. Corneal swelling then slowed, and in the final hour of a 3-hour exposure to K(+)-free tear solution, the corneas deswelled at about 10 microns/h. The data indicate that potassium is a necessary solute for the maintenance of normal corneal thickness. The results suggest that a lacrimal dysfunction that would cause a decrease in the potassium content of tears may influence corneal thickness and also suggest that the inclusion of potassium in artificial tears is important. PMID- 1608601 TI - Comparative studies of furosemide effects on membrane potential and intracellular chloride activity in human and rabbit ciliary epithelium. AB - Furosemide (1 mM), a potent loop diuretic, caused a 10-mV (n = 14) depolarization of the intracellular potential difference (PDI) of isolated rabbit ciliary epithelium (CE), but produced a 9-mV (n = 5) hyperpolarization of PDI of isolated human CE. In rabbit CE, furosemide consistently depolarized PDI by 13, 7 and 8 mV in HCO3(-)-free Ringer, Na(+)-free Ringer and after BaCl2 treatment, respectively. The depolarization of PDI was reduced to 2 mV (n = 11) in Cl(-) free conditions. A hyperpolarization of PDI caused by furosemide that was quantitatively similar to that seen in normal Ringer also occurred in human CE during immersion in HCO3(-)-free Ringer, Na(+)-free Ringer and after BaCl2 treatment. There was a small hyperpolarization (3 mV) of PDI in Cl(-)-free conditions. Human or rabbit tissue-cultured nonpigmented ciliary epithelial cells were loaded with the Cl(-)-sensitive fluorophore 6-methoxy-N-(3-sulfopropyl) quinolinium (SPQ) in hypotonic solution (145 mosm) for 4 min at 37 degrees C. Furosemide decreased intracellular Cl- fluorescence activity of both human and rabbit ciliary epithelial cells by 30 +/- 5 (n = 8) and 25 +/- 7% (n = 13), respectively, when the cells were immersed in Cl(-)-rich solution. It is suggested that a furosemide-sensitive Cl- movement exists in both rabbit and human CE, although the mode of Cl- movement to the aqueous across CE may differ between these species. PMID- 1608603 TI - [Stress proteins in medicine]. AB - The stress, or heat-shock proteins are essential for the homeostasis of living cells. Their role in the intracellular transport, refolding, or elimination of proteins becomes especially important after any unusual stimuli (stress) of the cell. This central role explains why stress proteins represent one of the most conservative structures of living cells. Human and bacterial stress proteins also show a homology as high, as 50%. This structural similarity links the immune responses against bacterial infections with a number of autoimmune diseases, such as lupus erythematosus, rheumatoid arthritis and insulin dependent diabetes mellitus, IDDM. In the end of our review we also discuss the possible role of stress proteins in protection against cardiac ischaemia and their putative role in aging. PMID- 1608604 TI - [Accurate assessment of myocardial viability: complementation of Thallium-201 scintigraphy with a subsequent reinjection study]. AB - Persistent myocardial thallium perfusion defects 3 to 4 hours after stress do not represent irreversible ischemia in every case. In many instances signs of reversibility show up 8-72 hours later or after rest reinjection. Authors performed additional investigations of redistribution in 64 patients with persistent defects. Rest reinjection was given to 11 patients and delayed redistribution was followed in the others. Persistent perfusion defects improved or disappeared in 13 percent of myocardial segments and 38 percent of patients. In 18% of segments late reverse redistribution was observed. The assessment of patients' state was significantly influenced by the results of the additional investigations in 19% of cases. Authors suggest that important information can be obtained about the viability of the myocardium by the extended studies even with the common planar method. PMID- 1608606 TI - [Rational means of the determination of costs and etiological diagnosis of community-acquired pneumonia]. AB - The cost and effectiveness of examinations (sputum staining and culturing, antitest determination for Influenza A and B, RSV, Adenovirus, Chlamydia psittaci and pneumoniae, Coxiella burnetii, Mycoplasma pneumoniae and Legionella pneumophila, and determination for Streptococcus pneumoniae antigen) performed to explore the aetiology of community-acquired pneumonia in the case of 258 hospitalised patients were analysed. The aetiology could be determined in 44.2% of the cases. On the basis of prevailing prices in 1986-88 one pneumonia case with determinable aetiology costs 8111 Forint. The authors have come to the conclusion that in the present epidemiological situation in this country it is not worthwhile to look for so-called non-bacterial microorganisms routinely, because of their rarely occurrence (16.7%) the cost per one positive finding is unrealistically high. Comparing the cost and the practical use the examinations applied the rational choice seems to be to culture the sputum with deep airway origin and to determine the Streptococcus pneumoniae antigen routinely. In the case of suspicion of non-bacterial origin to perform complement fixation test for Mycoplasma pneumoniae and in a severe clinical state to culture the blood is recommended. PMID- 1608605 TI - [The effect of low density lipoprotein (LDL) on NO formation and on arginase activity in mouse peritoneal macrophages]. AB - A large body of the evidence is available to the causative relationship between the elevated blood plasma concentrations of LDL and the atherogenesis. The oxid LDL (modified LDL) is internalized more rapidly by the macrophages, and there is now substantial evidence that the modified LDL is actually present in atherosclerotic lesions. Recently it has been proved that the endothel cells and monocyta/macrophages generate nitric oxide (NO) from arginine, and that the LDL inhibits the formation of NO in endothel cells. The authors found that the human LDL in vitro exerts an inhibitory effect on the formation of NO in murine PED (peritoneal exudate cells) and synchronously severalfold increasing of the arginase activity in the culture media. Both effects of LDL proved to be dose dependent and the oxid-LDL has been found to be more effective. The increased activity of arginase provides a very likely explanation for the reducing of NO production in macrophage treated by LDL. The reducing or blocking of NO-formation causes a local vasocontraction which induces clinical symptoms. PMID- 1608607 TI - [Studying the role of Helicobacter pylori infection in recurrent abdominal pain in children]. AB - The authors studied the role of Helicobacter pylori at recurrent abdominal pain in childhood. Helicobacter pylori infection hasn't been found at the 42 examined children. The endoscopy showed esophagitis in 34 cases. The quick urease test, the histological examination, and the bacterial culture are proposed to carry out in ulcus duodeni, gastritis typ. B ulcus ventriculi and not necessary to carry out if the endoscopy shows only esophagitis--emphasize the authors. PMID- 1608608 TI - [Honoring the memory of Olivecrona]. PMID- 1608609 TI - [Famous persons suffering from rheumatism]. PMID- 1608610 TI - [Ethical-scientific views on the use of human fetal tissues]. PMID- 1608611 TI - [Parasystole?]. PMID- 1608612 TI - [Clinical aspects of magnesium]. AB - Magnesium is the second most important intracellular cation after potassium in the human cell. Its pathologic and therapeutic role is well established in a large number of chronic conditions as vascular heart diseases, arrhythmias, hypertension, nephrolithiasis, diabetes mellitus, alcoholism, as well as in liver and pancreatic diseases. A broad spectrum of different clinical aspects and need of supplementation of magnesium is reviewed by the authors. Since suitable preparations are not available in the market the substitution of magnesium can cause difficulties in the practice. PMID- 1608613 TI - [Ultrasonic screening for congenital hip dysplasia]. AB - 1200 neonatal hips were examined by ultrasound and 30 dysplastic hips (2.5%) were detected, which required immediate treatment. Almost half of these dysplastic hip joints (1%) did not show any clinical signs of instability and had negative family/obstetrical history. These "silent" cases would not have been diagnosed and would not have got their early therapy without the ultrasound screening. The results of this investigation support the necessity of hipsonographic screening of all newborns. PMID- 1608615 TI - [Water enema in colonic ultrasonography]. AB - The transabdominal ultrasonography has less importance in the diagnosis of colonic tumors. To increase the diagnostic efficiency, the authors examined the colon with ultrasound - during water enema. They found 5 tumors and 4 polyps from 85 patients. They found, that this method is suitable for the intraluminal tumors' diagnosis. They want to investigate the other changes of the intestinal wall in the future. PMID- 1608614 TI - [Comparison of the diagnostic value of different tumor markers in prostatic cancer patients]. AB - The author compared the tumour markers of hundred virginell prostatic cancer patients. There were investigated the activity of prostatic acid phosphatase (SP) and its isoenzyme (SPP) by enzymatic method (PAP) as well. The concentration of prostatic specific antigen (PSA) was determined too. The sensibility of markers are growing on the row, SP, SPP, PAP, PSA. Summarising the results, the determination of PAP together with PSA seems to be not necessary. Because of the low price of SP, SPP their determinations is indicated in selected cases. Regarding of costs-benefit the author advises selected investigations in different stage and in different indications. PMID- 1608617 TI - [Tamas Kolozsvari Jordan, balneologist (1539-1585)]. PMID- 1608616 TI - [Current methods in the diagnosis of adult-age cystic fibrosis]. AB - An 19 year old male patient with cystic fibrosis is reported. The clinical, pathogenetic, anatomical features and literature data are reviewed. Attention is called to recent diagnostic facilities. PMID- 1608618 TI - [From the history of public health in the Baltic states]. PMID- 1608620 TI - [Day of Nursing 1992. "Healthy aging"]. PMID- 1608619 TI - ["and one is never praised..."]. PMID- 1608621 TI - [Aging, care, society ... and a person. The motivation of the aged patient in the hospital--or "is this still worthwhile?"--a plea for the realization of nursing principles]. PMID- 1608622 TI - [Care of the aged--a task for certified nursing personnel]. PMID- 1608623 TI - [From my own point of view. Views and considerations on student editorship]. PMID- 1608624 TI - Environmental health issues in otolaryngology-head and neck surgery. PMID- 1608625 TI - Environmental pollution and the health of children. PMID- 1608626 TI - The role of scientific research in risk assessment and risk management decisions. AB - Risk-based decisions are an integral part of societal efforts to protect the public from the harmful health effects of environmental pollution. Scientific information about the magnitude and extent of risks experienced by people and about the causes of those risks is a critical factor in setting priorities and choosing cost-effective mitigation strategies. To be effective in strengthening risk assessment and risk management decisions, research must focus on developing four types of predictive tools: (1) methods to screen and characterize toxicity; (2) biologically based dose-response models; (3) physiologically based pharmacokinetic models; and (4) integrated human exposure models. This approach is the key to reducing the uncertainties currently associated with many environmental health problems. PMID- 1608627 TI - Atmospheric pollution. AB - Air pollution has been directly responsible for increases in mortality and morbidity in the general population during periods known as episodes, when pollutant levels were elevated well above those that occur on a regular basis. The major concern today regarding pollution and health is, however, more subtle- namely, whether the lower levels of pollution to which we are exposed daily are harmful to health. It is extremely difficult to relate specific health problems to specific pollutants, because other environmental and lifestyle factors may contribute to decrements in health. Furthermore, people are generally exposed to mixtures of pollutants, making it difficult to extract the effects caused by individual components, or to determine which combinations are the most hazardous. Community air pollution results from various sources: mobile sources, such as vehicles; stationary sources, such as power plants and factories; and indoor sources, such as building material. Complicating the picture is the fact that many chemicals released into the air may react, producing additional secondary pollutants. This article provides an overview of the major air pollutants that may be of concern in terms of public health. PMID- 1608628 TI - Sick building syndrome and related workplace disorders. AB - It has been estimated that as many as 1.2 million commercial buildings have characteristics of sick building syndrome. That is, persons who work in these buildings describe a cluster of symptoms--irritation of eyes, nose, throat, and skin, respiratory ailments, headaches, dizziness, confusion, and unusual odor or taste sensations--that occur during occupation of the building but diminish when these persons leave these buildings. There have been a number of factors that have been implicated in the development of sick building syndrome. These include type of building ventilation, light intensity, tobacco smoke, wall-to-wall carpeting, crowding, work satisfaction, gender, and presence of volatile organic compounds. Sick building syndrome has many signs and symptoms of other workplace disorders (e.g., neurotoxic disorders, mass psychogenic illness), each of which manifest in rather imprecise psychological and somatic symptoms. There are, however, specific characteristics that distinguish these disorders. It is likely that the development and persistence of the sick building syndrome is not caused solely by building characteristics or simply a result of psychological variables. Rather, a synergistic relationship exists between building, environmental, and individual factors. PMID- 1608629 TI - Toxicology of upper aerodigestive tract pollutants. AB - The field of environmental toxicology has become quite important to the study of environmental health in human beings. The stability of the ecosystem in which we live is threatened by the nearly 5 million chemical compounds that have been synthesized worldwide, many of which have real or potentially toxic effects on the environment and on life forms. Four major groups of chemicals--metallic elements, nonmetallic elements, organic compounds and inorganic compounds--have certain agents within them that are known toxins to human beings. Some of these agents have an as yet unknown effect, whereas others have been well characterized. They can be found in the workplace, home, and outdoors, and many are unseen and odorless. In the past, most agents have been described in terms of their carcinogenic potential or major toxic effects on organ systems. It is now likely that the important characterization of some of these agents referrable to the upper aerodigestive tract should be at their receptor sites and identify the very discrete and small effects on these sites and their cumulative effects. The concept of threshold is probably an arbitrary one because to date these discrete effects have not been studied. Susceptibility on an individual basis probably varies from low to high, depending on the patient's immunologic and defense mechanisms and the existence of congenital or acquired risk factors. New attention must be given to more subtle effects on the upper aerodigestive tract (i.e., sinusitis and laryngitis) in view of the potential effects of certain toxic agents on these tissues. PMID- 1608630 TI - Environmental influence: potential interactions. PMID- 1608631 TI - Indoor air quality: a consumer protection issue. AB - In the last decade, the quality of indoor air has become a consumer protection issue. A Consumer Federation of America (CFA) study found that consumer knowledge about indoor air issues is limited. Although there is authority under existing statutes to address some aspects of the indoor air problem, consumer advocates and health professionals are supporting additional regulations and legislation. Such measures are aimed at reducing pollutants, affecting the operation of buildings, providing more information to consumers, and directing the federal government to conduct additional research and embark on programs to address indoor air pollution. PMID- 1608632 TI - Hearing: the effects of noise. AB - We live in a noisy world. The clamor and din of modern society has increased in variety, if not in prevalence and intensity, in the past decades, making noise America's most widespread nuisance. Excessive noise exposure annoys individuals, produces stress, impairs the ability to communicate, interferes with work and play activities, and, in high enough doses, produces permanent damage to the auditory system, which leads to significant hearing loss. Noise exposure associated with the workplace has been known to produce hearing loss for centuries. More than 20 years ago the U.S. Department of Labor promulgated regulations designed to protect the hearing of employees who work in noisy environments. However, these regulations failed to consider noise exposures outside the workplace, and recent evidence suggests that these exposures are potentially hazardous for millions of Americans. The most important sources of nonoccupational noise exposure are hunting and target shooting, listening to amplified music through headphones, and attendance at rock concerts. For each source, an assessment of risk of hearing loss is made. PMID- 1608633 TI - Hearing: the effects of chemicals. AB - Recent studies of human beings exposed to environmental chemicals, as well as experimental animal studies, have identified a number of chemical agents that are commercial products, chemical intermediaries, waste products, or contaminants that are potentially ototoxic. The classes of compounds discussed in this review include organic solvents, asphyxiant gases, and heavy metals that are present in the environment as industrial pollutants or byproducts. Both human and animal investigations are summarized in discussing the actions of these ototoxic compounds. The suggested gaps in our knowledge are highlighted to help direct future research. PMID- 1608634 TI - Otoneurologic disturbances caused by solvent pollution. AB - Subjects exposed to industrial solvents may experience vertigo and nausea. Solvents are usually volatile hydrocarbon compounds, which are important parts of everyday life in a modern society. They may also cause neurastenia, personality changes, and reduced intellectual capacity. The syndrome that may develop was formerly named psycho-organic syndrome (POS), but in modern terminology it is called chronic toxic encephalopathy (CTE). The syndrome develops slowly, and during the first years no pathological findings will be found using various test batteries. Somewhat later, when the syndrome still might be reversible, psychometric, auditory, and otoneurologic testing may well unveil disturbances within the posterior fossa structures. Animal experiments suggest one site of effect for solvents to be within the cerebellum and brainstem regions with close relationship to the gamma-amino-butyric acid (GABA) transmission. In the otoneurologic test battery, visual suppression and smooth pursuit are of extreme value, as are some auditory tests such as discrimination of interrupted speech and cortical response audiometry using frequency glides as stimuli. Dynamic posturography and magnetic resonance imaging (MRI) have recently proved valuable in the diagnosis. Research is needed concerning the most efficient test battery for early detection of solvent-induced lesions. During further research it is important to unveil other toxic agents, like heavy metals and alcohol, and their damage to the central nervous system and to make comparisons between these substances and the lesions caused by hydrocarbon solvents. PMID- 1608635 TI - Effect of environmental pollutants on taste and smell. AB - Various man-made and naturally occurring chemicals and substances can modify the chemosensory systems of animals and man. This article provides an overview of research studies that investigate the impact of pollution on taste and smell perception. Acute and chronic alterations in taste and olfaction are discussed for solvents, herbicides, fungicides, pesticides, disinfectants, germicides, soil fumigants, dyes, pharmaceuticals, textile wastes, smog, tobacco smoke, perfumes, flavors, plastics, synthetic rubber, and other industrial substances. The mechanisms by which pollutants may cause physiologic and biologic changes are highlighted. Natural detoxification systems are discussed, as well as treatments for chemosensory deficits. PMID- 1608636 TI - The impact of pollution on the voice. AB - Pollution is responsible for the presence of toxic substances and conditions throughout our environment. Inhalation of toxic pollutants may affect the voice adversely by direct laryngeal injury, by causing pulmonary dysfunction that results in voice maladies, or through impairments elsewhere in the vocal tract. Ingested substances--especially those that have neurolaryngologic effects--may also adversely affect the voice. Non-chemical environmental pollutants such as noise may also be responsible for voice abnormalities. Most of the information about the effects of pollution on the voice is anecdotal. Equipment and techniques that permit valid, reliable voice research have recently become available; and studies on the impact of pollution on communication, and specifically on voice, should be encouraged. PMID- 1608637 TI - Effects of pollution on swallowing: how little we know. AB - Swallowing is an essential function of the upper alimentary tract. It is highly complex, requiring precise coordination of numerous nerves and muscles of the oral cavity, pharynx, larynx, and esophagus. Swallowing is integrated with other physiologic functions, including mastication and respiration. Impairments of swallowing may result from many different structural or physiologic disorders. Little is currently known about the direct effects of pollution on swallowing. Structures critical to swallowing, however, are vulnerable to damage by environmental hazards such as exposure to ionizing radiation or intake of toxins by ingestion or inhalation. The relationship of swallowing to environmental lung disease is an area of particular interest because impaired swallowing may result in aspiration of food particles into the lung, and because pollutants may hamper airway defense mechanisms. In this article, we discuss the possible impact of selected environmental agents on swallowing and suggest future directions for research. PMID- 1608638 TI - Pollution: the nose and sinuses. AB - The nose and sinuses are constantly exposed to the huge quantities of gases needed to maintain life. Not only is the human nose well-equipped to warm and humidify this inhaled air, but it is also uniquely able to clean much of it. Any material other than physiologic amounts of oxygen, nitrogen, carbon dioxide, and water that accompanies the airstream can be considered a pollutant, and this pollutant could potentially injure the individual. The following discussion will review the defense mechanisms that allow the nose and sinuses to protect the lower airways. The effects of pollutants on the respiratory mucosa will then be described, including some recent trends in those effects. These trends include specific population consequences of indoor and outdoor air pollution, and changes in risk for individuals in several occupations. Throughout these discussions, specific areas that would benefit from further research will be mentioned. PMID- 1608639 TI - Effects on the upper respiratory passages. PMID- 1608640 TI - Age-related vulnerability. AB - This presentation considers the vulnerability of the upper alimentary and respiratory tracts to environmental insults during aging. A specific example, salivary gland secretion, is discussed. Available data suggest that while aging per se does not affect salivary performance adversely, it does appear to compromise the glands in such a way that older persons are more vulnerable to exogenous factors that can reduce secretory capacity and, consequently, diminish oropharyngeal health. PMID- 1608641 TI - System interactions of air pollutants. AB - The impact of system interactions and simultaneous or sequential exposure to various air pollutants, both man-made and natural ones, requires greater concern in the interpretation of the total adverse impact of various air pollutants. It is clear that there are highly significant system interactions with exposure to various air pollutants, and these must be considered very carefully in the evaluation of their adverse health effects. PMID- 1608642 TI - Keloid. PMID- 1608643 TI - Sensory testing of pathophysiological mechanisms of pain in patients with reflex sympathetic dystrophy. AB - The incidence of 3 sensory abnormalities was studied among 17 patients with a diagnosis of reflex sympathetic dystrophy (RSD) and 14 patients with persistent limb pain following trauma; the extent to which the 3 abnormalities were associated with each other and with the intensity of spontaneous clinical pain were also studied. These abnormalities included (1) heat-induced hyperalgesia (54.8% of 31 patients tested); (2) low-threshold A beta-mediated (45.2%) or high threshold (54.8%) mechanical allodynia; and (3) slow temporal summation of mechanical allodynia (10 of 29 patients tested). These 3 sensory abnormalities occurred to widely varying extents and were not reliably associated with each other. As hypothesized, patients with temporal summation had significantly more intense spontaneous pain than those who did not demonstrate this sensory characteristic. In contrast, the presence or absence of thermal hyperalgesia and type of allodynia did not appear to influence the intensity of spontaneous pain. These results indicate that variable types of primary afferents (i.e., A beta versus A delta, C) and/or varying extents of abnormal spatial summation mechanisms trigger pain responses among RSD patients and that at least one of these, slow temporal summation, is likely to contribute to the intensity of a patient's ongoing pain. PMID- 1608644 TI - The use of electromyography and muscle palpation in the diagnosis of tension-type headache with and without pericranial muscle involvement. AB - The Headache Classification Committee of the International Headache Society recently issued revised diagnostic criteria for headache disorders. According to these criteria, tension-type headache may be subclassified depending upon whether pericranial muscle disorder is found. The presence or absence of pericranial muscle disorder was to be determined by palpating the muscles for tenderness or by measuring electromyographic (EMG) activity. In this study, pericranial muscles were palpated, and EMG activity was measured in 27 episodic tension-type headache patients and 32 headache-free controls. All testing was done while the subjects were in a headache-free state. Muscle tenderness was positively associated with the diagnosis of tension-type headache. Headache subjects exhibited significantly higher levels of temporal EMG activity compared to controls, but EMG data were of little use in assigning individual subjects to diagnostic groups. Measures of muscle tenderness and hyperactivity were only weakly associated. Pericranial muscle tenderness and elevated EMG activity may index different aspects of abnormal muscle function. PMID- 1608645 TI - Possible startle response contamination of the spinal nociceptive withdrawal reflex. AB - The objective of this study was to examine the possibility that the spinal nociceptive withdrawal reflex, otherwise known as the RIII reflex, is contaminated by the startle response, which is a non-pain-related supraspinal response. Startle response contamination of the RIII reflex would seriously compromise the RIIIs ability to measure spinal nociceptive processes in man, since a change in the startle response affecting EMG amplitude in the RIII latency range would be erroneously interpreted as a change in a spinal nociceptive process. EMG responses evoked by electrical stimulation of the sural nerve were recorded from the orbicularis oculi, neck, biceps, and biceps femoris muscles in 31 healthy human volunteers. The startle response was elicited under conditions often used to record the RIII reflex. Procedures are described that will completely eliminate the startle response. Comparisons between subjects that did and did not elicit a startle response revealed that the startle does not appear to significantly contaminate the biceps femoris RIII reflex, at least when performing group comparisons. There are, however, situations not dealt with in this study in which the startle might significantly contaminate the RIII reflex, such as patients with pre-existing negative emotional states, experimental procedures that induce fear and/or anxiety, and single case studies. It is important, therefore, that investigators using the RIII reflex be cognizant of the startle response and take appropriate precautions to monitor and if necessary eliminate the startle before attributing a change in the RIII reflex to a spinal nociceptive process. PMID- 1608646 TI - Pain complaint and the weather: weather sensitivity and symptom complaints in chronic pain patients. AB - Chronic pain patients frequently report that weather conditions affect their pain; however, no standardized measures of weather sensitivity have been developed. We describe the development and use of the Weather and Pain Questionnaire (WPQ) which assess patient sensitivity to meteorologic variables defined by the National Weather Service (e.g., temperature, precipitation). Seventy chronic pain patients (59% females) with an average age of 43 years completed the WPQ. The instrument was revised using factor analysis to produce a Weather Sensitivity Index (WSI) (48% of variance) with high internal consistency (0.93) and test-retest reliability (r = 0.89). Reporting patterns suggested that patients could reliably identify which meteorologic variables influenced their pain but could not reliably determine which physical symptoms were consistently affected. The most frequently reported meteorologic variables which affect pain complaint were temperature (87%) and humidity (77%). The most frequently reported physical complaints associated with the weather were joint and muscle aches (82% and 79%, respectively). Patients labeled as being 'weather sensitive', defined by greater than median scores on the WPQ, reported significantly greater pain intensity, greater chronicity of pain problems, and more difficulties sleeping than patients with low scores on the WPQ. No differences in gender, education level, disability status, or global psychological distress were found. Results are discussed with respect to physiological and psychological mediating variables. PMID- 1608647 TI - Quantitative determinations of sensory and pain thresholds on human oral mucosa by argon laser stimulation. AB - High-energy light from an argon laser was applied to human oral mucosa in order to investigate regional pain sensitivity. Significant regional differences in sensory and pain thresholds were observed between the test sites on the hard and soft palatal mucosa, the buccal mucosa, the tongue, the lower lip, and the skin on the hand. Pain thresholds were lowest on the tip of the tongue and highest on the hard palate. Sensory and pain thresholds were influenced by different stimulus parameters: pulse duration and laser beam diameter. Blackening of the mucosa in regions with high optical reflectance, such as the hard palate, increased light absorption and, hence, reduced both thresholds significantly. Reflectance spectrophotometric measurements indicated that the hard palatal mucosa reflected argon laser light about 1.5 times more than the tip of the tongue. The different threshold values could, in part, be ascribed to different reflectance and absorption properties of the mucosal areas but also indicated substantial regional variation in pain sensitivity of the human oral mucosa. Measurement of laser thresholds is an appropriate and standardized method for investigating sensory differences in human oral mucosa and may be used to study various pain conditions, e.g., burning mouth syndrome. PMID- 1608649 TI - Temporal processes of formalin pain: differential role of the cingulum bundle, fornix pathway and medial bulboreticular formation. AB - Subcutaneous injection of formalin produces a characteristic biphasic pain response. An early phase develops in the first 5 min after injection; the pain then decreases for 10-15 min, followed by a gradual rise to a stable plateau that lasts about 1 h. Rats were injected with 1 microliter of 2% lidocaine or saline into the anterior cingulum bundle at 0 (immediately), 10 or 30 min prior to formalin injection, or 10, 20 or 30 min after formalin injection, and tested for analgesia in the late phase of the formalin test, 30-70 min after formalin injection. A time-dependent increase in analgesia was obtained when lidocaine was injected into the cingulum at periods ranging from 10 to 30 min after formalin injection, reflecting an anaesthetic duration of less than 20 min. When lidocaine was injected 0 or 10 min prior to formalin injection, a time-dependent increase in analgesia in the late phase was again observed. In these groups, lidocaine should have blocked cingulum activity during the early but not the late phase. The role of the fornix pathway and the medial bulboreticular formation in mediating formalin pain was also examined. Lidocaine produced analgesia in the late phase when injected into the fornix prior to formalin injection but had no effect when administered after it. In contrast, when lidocaine was injected into the medial bulboreticular formation it produced analgesia in the late phase when administered after formalin injection, but not prior to it. Taken together, these results suggest that the late pain response to formalin is in part dependent upon plasticity in the central nervous system which occurs during the transient early phase. PMID- 1608648 TI - Intrathecal injection of acetylsalicylic acid, salicylic acid and indomethacin depresses C fibre-evoked activity in the rat thalamus and spinal cord. AB - It was aimed to assess if intrathecal (i.t.) injections of acetylsalicylic acid and salicylic acid depress C fibre-evoked activity in the sensory part of the nociceptive system. In rats under urethane anaesthesia, activity was elicited in single neurones in the dorsomedial part of the ventral nucleus (VDM) of the thalamus and in ascending axons of the spinal cord by supramaximal electrical stimulation of the sural nerve. Acetylsalicylic acid and salicylic acid injected i.t. significantly reduced the activity evoked in thalamic neurones. The maximum depression amounted to about 50% of the activity evoked in the controls and was produced by acetylsalicylic acid at a dose of 50 micrograms (0.28 mumol)/rat and by salicylic acid at a dose of 37.5 micrograms (0.27 mumol)/rat. Indomethacin injected i.t. also reduced C fibre-evoked activity in the thalamus in a dose dependent fashion, 100 micrograms producing a 50% depression. Salicylic acid (37.5 micrograms/rat, i.e.) depressed C fibre-evoked activity in ascending axons but had no effect on A beta fibre-evoked activity. It is concluded that i.t. injection of acetylsalicylic acid selectively inhibits nociceptive impulse transmission in the spinal cord by an action of the salicylic acid moiety. It is possible that prostaglandins are involved in the central action of salicylic acid. PMID- 1608650 TI - Antinociceptive effects of acute and 'chronic' injections of tricyclic antidepressant drugs in a new model of mononeuropathy in rats. AB - The tricyclic antidepressant drugs (TCAs) are commonly used in the treatment of chronic, especially neuropathic, pain. We evaluated their possible effect on a new model of neuropathic pain-related behaviour induced by ligatures tied loosely around the common sciatic nerve. The effects of 3 TCAs with different monoaminergic spectra (clomipramine, amitriptyline and desipramine) were assessed 2 weeks after surgery, the time of the maximum hyperalgesia, on a 'phasic' test (vocalization threshold to paw pressure) and on a 'tonic' test (score of the spontaneous pain-related behaviour). TCAs were acutely (0.5 and 2 mg/kg, i.v.) and 'chronically' injected (7 injections, once every half-life of the drug: 0.75 and 1.5 mg/kg, s.c., for clomipramine and 1.5 and 3 mg/kg, s.c., for amitriptyline and desipramine). Acutely injected clomipramine and amitriptyline (0.5 mg/kg, i.v.) and desipramine (2 mg/kg, i.v.) showed an antinociceptive naloxone-reversible effect, assessed by an increase in the vocalization threshold to the paw pressure test and, for amitriptyline, by a decrease in tonic pain scores. Chronically injected TCAs induced a significant and progressive increase in the vocalization threshold with a time course parallel to that of their suspected plasma or nerve tissue levels: (i) a regular increase of scores for the first 3-4 injections, (ii) then a plateau until the last injection, and (iii) a progressive decrease with a dose-dependent duration of the effect, longer than that obtained with a corresponding acute dose. This study showed that in this new model of mononeuropathy, acutely and chronically injected TCAs induce an antinociceptive effect and suggested that their analgesic action could be related to the monoaminergic spectrum of the drug in relation to the opiate systems. PMID- 1608651 TI - [Langerhans cells and presentation of antigens]. AB - Epidermal Langerhans cells express only very few Class I major histocompatibility complex (MHC) antigens, whose ability to present peptides released from the breakdown of endogenous proteins has not been investigated to date. Langerhans cells strongly express a "nonconventional" Class I molecule, the CD1a antigen. The role played by this antigen on the surface of Langerhans cells remains unelucidated: either release or uptake of peptides derived from the body has been speculated. Langerhans cells also express Class II MHC antigens and in vitro freshly recovered Langerhans cells are capable of capturing antigens, processing them and presenting the resulting peptides associated with Class II MHC molecules to immunocompetent cells. This property is not, however, permanent. Cultured Langerhans cells are no longer capable of processing antigens because they lose their ability to (i) acidify endosomes and (ii) produce the alpha, beta and invariant chains of class II MHC molecules. Cultured Langerhans cells acquire the capacity of stimulating T lymphocytes. This contrast between the in vitro properties of freshly recovered and cultured Langerhans cells may reflect in vivo differences between epidermal Langerhans cells and Langerhans cells which have migrated to regional lymph nodes. PMID- 1608652 TI - [Culture of human melanocytes. Its contribution to the knowledge of melanocyte physiology]. AB - Culture techniques for normal human melanocytes have been developed over the last ten years. This in vitro model for studying pigment-producing cells can be expected to provide major advances in the knowledge of cell-to-cell anc cell-to matrix interactions, melanocyte and melanin biology, pathophysiology of pigment disorders, and malignant melanomas. Melanocyte cultures have already shed new light on keratinocyte-melanocyte interactions within the epidermal melanin unit by showing that keratinocytes produce "melanotrophic factors" which modulate growth, melanin production, and dendricity of melanocytes. Melanocyte cultures also enable in vitro studies of melanocyte responses to ultraviolet radiations and of the biologic messengers involved in these responses. Lastly, they provide a means for investigating endocrine and paracrine mechanisms involved in the regulation of melanogenesis, including the role of melanotropins, estrogens and vitamin D. Improved knowledge of the molecular biology of melanocytes provides hope for rapid advances in the understanding of tyrosinase and posttyrosinase regulation of melanogenesis. Lastly, melanocyte cultures can be expected to find useful applications in the pathophysiologic study of pigment disorders and of pharmacologic modulation of skin pigmentation. PMID- 1608653 TI - [The dermo-epidermal junction and its acquired and hereditary pathology. A few recent advances]. AB - The dermoepidermal junction (DEJ) is a key structure in the skin. Many acquired and inherited diseases affect the DEJ. New insight has been gained into the chemical composition of the DEJ of which at least 20 protein components have been identified to date. Some components of hemidesmosomes, which are critical DEJ structures, have also been identified. Hereditary epidermolysis bullosa is a heterogeneous group of DEJ disorders. Studies are beginning to shed light on the molecular mechanisms of these diseases. Dystrophic epidermolysis bullosa is due to alterations in the collagen IV molecule which is an essential component of anchoring fibrils. Several molecules, including BM-600 niceine, are apparently altered in the skin and other epithelia of patients with junctional epidermolysis bullosa. These molecules may be involved in the pathogenesis of inherited DEJ diseases with anomalies of hemidesmosomes. Lastly, DEJ antigens involved in a number of acquired bullous skin disorders (bullous pemphigoid, herpes gestationis, acquired epidermolysis bullosa...) have been identified recently. PMID- 1608654 TI - [The extracellular matrix and its regulation]. AB - The dermis is a differentiated connective tissue whose mechanical properties originate in a network of polymeric macromolecules associated to a variety of glycoproteins and proteoglycans. Each macromolecule contains specific recognition domains allowing their self-association and binding to other macromolecules and to the cell membrane receptors, through. Cell function is regulated by the transfer of information resulting from contact with the polymeric network, as well as by cytokines and growth factors. The structure of the genes encoding the different macromolecules and their regulation sequences are largely known. Various connective tissue disorders are due to alterations of these genes. PMID- 1608655 TI - [Dermo-epidermal interactions and skin pharmacology]. AB - Reconstruction of a living skin equivalent provides an in vitro model for the study of skin biology and pharmacology in a tissue organization whose cells differentiate similarly to skin cells in the body. This simplified skin equivalent, composed of normal or abnormal cells, is obtained in two steps: formation of a dermal equivalent is achieved first and this dermis is then covered with an epidermal equivalent. Each of these tissues, as well as the interactions between them, can then be studied. Using this model, we have demonstrated that normal fibroblasts promote epidermal growth, that psoriatic fibroblasts induce increased proliferation of normal keratinocytes, and that the effects of pharmacological agents (such as retinoids) on keratinocyte growth are modulated by fibroblasts. PMID- 1608656 TI - [Studying the mast cell. Recent data]. AB - In the light of recently published data, the mast cell can now be viewed as a key cell, not only in allergic reactions such as immediate hypersensitivity responses, but also in a broad spectrum of other biologic responses including host-parasite interactions, nonspecific inflammatory reactions, fibrosis, angiogenesis, tissue reconstruction, and wound healing. Nevertheless the molecular basis for the intervention of mast cells in many of these biologic responses is still unclear. Very recent studies have demonstrated that mast cells are capable of producing a wide range of cytokines, a property which may influence various physiologic, immunologic and disease processes. Furthermore, although substantial differences have been reported between mast cells located in different tissues, the reasons and mechanisms underlying this heterogeneity long remained obscure. The recent development of two original experimental approaches, i.e., in vitro culture of mast cells, mainly derived from mouse bone marrow precursors, and replenishment of mast cell-deficient mice, has provided new insight into the mechanisms by which tissue microenvironment influence of regulation mast cell phenotype. Extrapolation to humans of data obtained in rodents is, however, hazardous. In the review presented here, the most recent data from the literature provide the basis for outlining avenues of research which can be expected, in the near or remote future, to solve what mast cell experts term "the riddle of the mast cells". PMID- 1608657 TI - [DNA repair and related diseases]. AB - DNA-repair is a complex enzymatic process which enables all living cells to withstand the deleterious and mutagenic effects of most genotoxic agents. Defective DNA-repair is caused by mutations involving genes which encode the enzymes responsible for recognition and excision of DNA lesions. Some of these genes have been identified in humans. Several severe human diseases are caused by defective DNA repair affecting the entire genome (e.g. xeroderma pigmentosum and trichotiodystrophy) or only actively transcribed genes (Cockayne's syndrome). Some of these conditions are associated with extremely high rate of cancer. PMID- 1608658 TI - [Ultraviolet rays and the skin. Modulation of immune functions]. AB - Ultraviolet radiations (UV) are one of the most common environmental stimuli. In the skin, UVs induce selective biological alterations whose effects include suppression of the normal immune response. This immune suppression may play an important part in the development of skin cancers, infectious diseases, and autoimmune responses. The review presented here focuses on UV-induced biological disorders and on the role of UV-exposed epidermal cells in the mechanisms of immunosuppression. PMID- 1608659 TI - [Role of oncogenes and anti-oncogenes in dermatology]. AB - Cell growth is controlled by two types of genes, i.e., activating genes (oncogenes) and negative regulator genes (antioncogenes). Studies have shown that malignant transformation of a cell can result from either increased oncogene activity or decreased antioncogene activity. Current knowledge of genes relevant to dermatology is discussed. PMID- 1608660 TI - [Hereditary skin diseases: new genetic approaches]. AB - New powerful techniques capable of effective genome analysis are now available for the study of inherited skin disorders. In most instances, a biochemical defect in the patient points to the responsibility of a given gene in the occurrence of the disease. The role of this candidate gene is tested by genetic linkage studies, then confirmed by identification of the molecular gene defect and collection of evidence that this gene defect is causally related to the disease phenotype. This conventional genetic approach has succeeded in identifying the genes and molecular defects responsible for X-linked ichthyosis, epidermolysis bullosa simplex of Koebner and Dowling-Meara, albinism and piebaldism. When no biochemical clue is available, reverse genetics can be used to delineate the region of the genome that contains the disease locus, thus shortening the search for the candidate gene. This approach, occasionally aided by the presence of cytogenetic anomalies, has allowed to locate and identify the gene for Von Recklinghausen neurofibromatosis (NF1) and to demonstrate the existence of two loci genetically related to tuberous sclerosis. PMID- 1608662 TI - [Jacques Monod Conference 1991. "Vascular physiology in angiogenesis and defence mechanisms"]. PMID- 1608661 TI - [Skin metabolism]. AB - The skin, one of the organs which accounts for the largest proportion of total body weight, was long viewed only as a passive physical barrier between the body from the environment. Over the last ten years, many studies have demonstrated significant metabolic processes in the skin, due in particular to the effects of enzymes which are located mainly in the epidermis. This skin metabolism has a marked effect on percutaneous penetration of xenobiotics. In this review, enzyme activities detected in the skin and their location in the various skin layers are discussed, as well as the different in vitro and in vivo models for studying skin metabolism. Pharmacologic or toxic effects of active ingredients or their metabolites may be associated with the nature and magnitude of transformations of xenobiotics in the skin (first pass effect). The impact of skin metabolism on the effects of topically applied drugs and the factors capable of modulating skin biotransformations are discussed. The main difficulties faced by skin metabolism studies stem from the relatively complex structure of skin and in the low levels of enzymatic activities. PMID- 1608663 TI - [Cholecystokinin antagonists: anxiolytic drugs of the future]. PMID- 1608664 TI - Evaluation of a blood culture medium BHI-S-Lysis for BCB Release System Roche. AB - The new blood culture medium BHI-S Lysis for the BCB Release System (F. Hoffmann La Roche AG., Basel, Switzerland), which lyses blood cells, was compared with the Hemoline performance Duo (BioMerieux, Marcy l'Etoile, France) including a diphasic medium and a modified Wilkins Chalgren broth. A total of 1998 sets were each inoculated with 7 ml of blood. In the laboratory, agar-coated paddles were attached to the BHI-S-Lysis. Overall, there was a statistically significant difference between the BHI-S-Lysis and the diphasic medium, or Wilkins Chalgren broth, in the recovery of clinically important microorganisms. The yield of pathogens with the BHI-S-Lysis, diphasic medium and Wilkins Chalgren broth was 115, 68 and 58, respectively. Staphylococci were detected by the BHI-S-Lysis significantly more frequently. Out of 50 bacteraemias, 12 were diagnosed with the BHI-S-Lysis only, three with the diphasic medium only, and three with the Wilkins Chalgren broth only. Contaminant isolates occurred with significantly greater frequency in the BHI-S-Lysis than in the two BioMerieux systems, in particular with coagulase-negative staphylococci. No speed advantage was present for all groups of micro-organisms and blood culture media. This good performance of the BHI-S-Lysis medium in detecting a larger number of pathogens should be confirmed by further evaluations. PMID- 1608665 TI - [Serological confirmation of HIV infections in hospital practice: analysis of indeterminate western blot results]. AB - Among 770 Western blots for HIV-1 confirmation on sera from subjects at high risk for HIV infection, 4.3% (33 cases) were indeterminate. Isolated, stable, reproducible anti-gp 160 reactivity, highly suggestive of a nonspecific reaction, was found in 16% of cases. There were three other probably nonspecific patterns with anti-gp 160 and either anti-gp 41 or anti-gp 120 reactivities and thin, atypical bands. Two patterns with anti-p24 and either anti-gp 160 or anti-gp 120 reactivities were consistent with HIV-1 seroconversion. Reactivity directed solely against gag products was seen in 18% of cases. The repeat test, performed in 16 cases, showed an identical pattern in 3 cases, a modified pattern in 3 cases, negative results in 9 cases, and seroconversion in 1 case. No case of HIV 2 infection was detected. Indeterminate Western blot results reflect nonspecific reactivity in most instances but should nevertheless lead to the exclusion of technical artefacts, seroconversion, and HIV-2 infection. PMID- 1608667 TI - [Recall of the importance of serological monitoring of children with suspected congenital toxoplasmosis]. AB - Emphasis is put on the need for repeating serologic tests at regular intervals until one year of age in infants with suspected congenital toxoplasmosis. In 11 of 33 cases, antibody titer changes were the only evidence of toxoplasmosis, a disease which may induce severe ocular lesions if appropriate treatment is not given. Although well-recognized as indispensable, serologic monitoring is not always performed; in one group of 326 infants with suspected congenital toxoplasmosis, 133 (41%) were not followed up for more than six weeks. PMID- 1608666 TI - The chemoprophylaxis of cerebrospinal meningitis using rifampin in a military population. AB - Since February 5th 1990, the prevention of secondary cases of cerebrospinal meningitis (CSM) in France has been obtained by the use of rifampin. Following the detection of a case of N. meningitidis of antigenic formula B:NT:P1.15,16 in a military population, 89 contacts subjects received 600 mg rifampin twice a day during 2 days. Meningococcal carriage rate was investigated by nasopharyngeal swab sampling of the 89 subjects and 62 non-contact controls from the same community. Twenty-three days after the initial case of meningitis, carriage rate was 5.6% for treated subjects and 37.1 for controls. Sero-grouping, serotyping and subtyping failed to detect the initial virulent strain; it demonstrated the heterogeneity of circulating strains. Since rifampin-resistant mutants may occur, two strains in the treated group, it is essential that chemoprophylaxis in a community be limited strictly to the contact subjects. PMID- 1608668 TI - Acute monocytic leukemia: prevalent cutaneous lesions. Two cases. AB - The authors report two cases of acute myeloid leukemia with prevalent cutaneous lesions. The positivity of granulo-monocytic antibodies and the exclusive cutaneous site of the lesions drove them previously to the diagnosis of histiocytic sarcoma. These cases stress the problem of the immunological identification of cutaneous lymphomas of "histiocytic" type. PMID- 1608669 TI - The preparticipation sports physical examination. PMID- 1608670 TI - Medical exclusion from participation in sports. PMID- 1608671 TI - The orthopedic component of the preparticipation examination. PMID- 1608672 TI - Sports injuries in childhood. AB - Participation in youth sports is relatively safe. Injuries become more frequent as the child gets older, bigger, and achieves higher skill levels. At the high school and collegiate levels, football has the highest injury rate followed by wrestling and gymnastics. There is no risk-free sport, and children tend to select the sports they wish to participate in without considering injury rates. Pediatricians should take an active role in injury prevention when covering sporting events as team physicians and as spectators. PMID- 1608674 TI - Anabolic-androgenic steroids and the adolescent. AB - This article has reviewed some of the hormonal and behavioral maturation that occurs during adolescence, which are characterized by remarkable physical changes and behavioral vulnerability. Risk taking of many varieties is common and drugs (including anabolic-androgenic steroids) form a part of the prevailing culture in many places. These steroids probably are not severe health hazards when taken intermittently and in low to moderate doses. The 17-alkylated derivatives are clearly the more likely to cause hepatotoxicity. Thus, the scare tactics formerly used (severe constitutional side effects) are doomed to failure. The tenuous link between these drugs and objective behavioral and addictive effects must be strengthened before health strategies based on this issue can be validated. Clearly, the lack of scientific information has impeded, if not precluded, the formulation of an effective health education strategy. The most potent deterrent to the use of steroid drugs by athletes must be the moral issue of fair play and maintaining a "level playing field." We strongly support directed research in these areas and hope that the credibility of the scientific community can be regained after its faulted "stop steroid use" campaigns based on the lack of steroid efficacy in bringing about desired results or on their dire consequences have been replaced with credible evidence to refute their use on these and other grounds. PMID- 1608673 TI - The acute management of minor soft tissue injuries. PMID- 1608675 TI - Sudden unexpected death in sports. PMID- 1608676 TI - The cerebrospinal fluid: physiologic aspects and alterations associated with bacterial meningitis. PMID- 1608677 TI - Management of penicillin-resistant pneumococcal infections. PMID- 1608679 TI - Complications of varicella requiring hospitalization in previously healthy children. AB - Between January 1, 1981, and December 31, 1990, 83 previously well children and 20 with stable underlying conditions were hospitalized because of complications of varicella. The mean hospital stay was 4.5 days and one child with pneumonia died. Skin or soft tissue infections and pneumonia were the most common complications. Central nervous system complications (15), dehydration (8) and Reye's syndrome (6) accounted for 75% of the nonsuppurative complications. Cellulitis (7), pneumonia (3) and encephalitis (3) were the most common diagnoses among the 20 children hospitalized greater than or equal to 7 days. No cases of Reye's syndrome were diagnosed after 1984. An increase in the number of soft tissue infections caused by Group A beta-hemolytic streptococci and involving an extremity was noted during the last 5 years. Chickenpox continues to cause significant morbidity in the pediatric population. PMID- 1608678 TI - Predictive value of the human immunodeficiency virus 1 antigen test in children born to infected mothers. AB - Our objective was to examine the utility of the human immunodeficiency virus (HIV 1) antigen test as an early predictor of HIV-1 infection among children born to infected mothers and to collect information about its performance as a diagnostic test. The Abbott HIVAG-1 Enzyme Immunoassay was used to analyze serial serum samples from patients enrolled in a longitudinal cohort study of children born to mothers infected with HIV-1. There were 85 subjects who were followed from birth whose HIV-1 infection status could be definitely determined as of March, 1990. Of these 22 (26%) were infected with HIV-1 and 63 (74%) were uninfected. Overall the sensitivity of the test was 77% (95% confidence interval (CI), 55 to 92%) and the specificity was 97% (95% CI, 89 to 99%). The positive predictive value of a single positive test was 89% (95% CI, 67 to 99%) and of two or more positive tests was 100% (95% CI, 50 to 100%). The sensitivity of the test varied greatly with age. For 36 children from whom sera were collected during the first month of life the specificity of the antigen test was 100% but the sensitivity was only 20%. Overall in the first 6 months of life the sensitivity was less than 50%. The Abbott HIV-1 antigen test is useful as an early predictor of HIV-1 infection in children whose mothers are infected. PMID- 1608680 TI - Imipenem-cilastatin vs. tobramycin and metronidazole for appendicitis-related infections. AB - The efficacy of imipenem-cilastatin was compared with that of tobramycin and metronidazole for the treatment of appendicitis-associated abdominal infections in children in an open, randomized trial. Two hundred eighteen patients between 2.5 and 16.8 years of age hospitalized for appendectomy because of suspected acute appendicitis were allocated to 5 treatment groups. The appendix was perforated in 54 (33.8%) of the 160 cases with appendicitis. All patients responded favorably to treatment. Infection in the wound occurred in 15 of 125 (12.0%) of those without preoperative antibiotic therapy and in 5 of 83 (6.0%) of those given imipenem preoperatively (P = 0.12; 95% confidence interval, -2.2 to 14.2%). C-reactive protein decreased significantly faster in those with perforated appendix treated with imipenem than in those treated with tobramycin and metronidazole (58.2 mg/liter vs. 89.4 mg/liter, P less than 0.05 on the third postoperative day). Imipenem-cilastatin was at least as effective and economically comparable as tobramycin and metronidazole for the treatment of appendicitis-associated infections in children. PMID- 1608681 TI - Usefulness of skin testing with mycobacterial antigens in children with cervical lymphadenopathy. AB - One hundred twenty-three children with chronic cervical lymphadenopathy were skin tested with purified protein derivative (PPD)-B (Mycobacterium intracellulare), PPD-Y (Mycobacterium kansasii), PPD-G (Mycobacterium scrofulaceum) (nontuberculous mycobacterial antigens (NTMags)) and PPD-T (Mycobacterium tuberculosis). Children with culture-confirmed mycobacterial disease had significantly larger reactions to NTMags and were 6 times more likely to have PPD B responses of greater than or equal to 10 mm than those with negative microscopy/culture results. Children with acid-fast bacilli present in clinical specimens but with negative culture results were 3 times more likely to have greater than or equal to 10 mm induration to PPD-B than those with negative microscopy/culture results. In all groups except those with culture-confirmed M. tuberculosis, responses to PPD-T were significantly smaller than those to the NTMags. We conclude that NTMags, particularly PPD-B, may be useful in diagnosing childhood mycobacterial cervical adenopathy; however, their usefulness in distinguishing disease caused by M. tuberculosis from that resulting from other mycobacteria is unknown. PMID- 1608682 TI - Thrombocytosis and thrombocytopenia in childhood bacterial meningitis. AB - To assess factors affecting the development of reactive thrombocytosis during bacterial meningitis, thrombocyte counts of 311 children with cerebrospinal fluid culture-positive bacterial meningitis were followed during hospitalization. Thrombocytosis (platelet counts greater than 500 x 10(9)/liter) was seen in 49% of the patients after the first week of treatment. Thrombocyte counts were higher in infants and in patients with long duration of illness before admission. Subdural effusion and cephalosporin therapy were associated with more pronounced thrombocytosis We found no relation between thrombocytosis and neurologic complications, but the patients who died developed thrombocytopenia instead of thrombocytosis. The difference between the thrombocyte curves of the surviving and dying patients might be utilized in predicting the final outcome in the severest cases of bacterial meningitis. We speculate that inflammatory cytokines, especially interleukin 1-beta, induce reactive thrombocytosis in bacterial meningitis. PMID- 1608684 TI - Etiology of acute lower respiratory tract infections in children in a rural community in The Gambia. AB - Approximately 500 children younger than 5 years old resident in 7 villages in a rural area of The Gambia were monitored closely for 1 year for episodes of acute lower respiratory tract infection (ALRI). Each episode was investigated with antigen detection techniques and antibody assays as well as culture for bacteria and viruses. A pathogen was identified in 76 (34.2%) of 222 cases with clinical signs of ALRI and in 34 (42%) of the 81 cases who, in addition, had radiologic evidence of ALRI. Evidence of infection with a bacterial pathogen, most commonly Streptococcus pneumoniae or Haemophilus influenzae, was obtained in 32 (14.4%) cases with clinical signs of ALRI (23.5% of those with radiologically proved pneumonia). Viral agents were cultured from 42 (19%) of 221 cases but also from 14 (14.6%) of 96 controls some of whom had minor symptoms of upper respiratory tract infection. In the absence of an outbreak of respiratory syncytial virus the viral agents recovered most often were influenza A and adenoviruses. PMID- 1608683 TI - Description of an adenovirus type 8 outbreak in hospitalized neonates born prematurely. AB - An adenovirus (Ad) type 8 outbreak was prospectively studied in a neonatal intensive care unit. Nasopharyngeal secretions were cultured weekly for viruses and clinical information was obtained daily in each infant. Eleven of 112 neonates were infected with Ad; 8 of 9 available isolates represented one variant of Ad 8. The median age at infection was 54 days and the median duration of virus shedding was 2 days. Seven of 11 infants had onset of new symptoms and/or required acute respiratory support; only 2 infants had eye disease. Maternal characteristics, race, gender, age at entry into study and respiratory distress syndrome at birth were similar for both groups. Ad-infected infants tended to have earlier gestations and lower birth weights. Ad-infected neonates stayed longer in the neonatal intensive care unit, required more days of respiratory support and were more likely to develop bronchopulmonary dysplasia. Thus an association was established between lung disease in premature neonates and Ad infection. PMID- 1608685 TI - Antibiotic therapy for cat-scratch disease: clinical study of therapeutic outcome in 268 patients and a review of the literature. AB - During 24 months in an uncontrolled, retrospective study of 268 patients with cat scratch disease (CSD), 202 were treated with 18 different antimicrobial agents. Criteria for antibiotic effectiveness were established. One or two antibiotics were taken separately for at least 3 to 5 days by 202 patients with CSD. Outcome was determined by follow-up examinations and telephone. Effectiveness of antibiotic therapy was based upon 3 or more days of therapy and clinical improvement of the patient with absence of and/or a decrease in malaise, fatigue, fever, headache, anorexia, lymphadenopathy and, in 90 patients, a declining or normal sedimentation rate. Of 18 different antimicrobials prescribed, 14 commonly used antibiotics were judged to be of little or no value in treatment of CSD. Four antimicrobials were efficacious. Efficacy of the three oral drugs in decreasing order was: rifampin 87%, ciprofloxacin 84%, trimethoprim sulfamethoxazole 58%. Gentamicin sulfate intramuscular was 73% effective. Antibiotic therapy can be considered for patients with severe cat scratch disease. Conservative, symptomatic treatment is recommended for the majority of patients with mild or moderate CSD. PMID- 1608686 TI - Zoonoses of house pets other than dogs, cats and birds. AB - In addition to dogs, cats and birds, which are the most frequent house pets, rabbits, rodents, fish and turtles are also vertebrate species that commonly share the home environment. Lizards, snakes and ferrets are less common pets. These species can transmit numerous diseases, especially to children who are more likely to be in close contact with them. The author presents a general review of zoonoses and potential zoonoses transmitted by rabbits, rodents and cold blooded vertebrates. Zoonoses transmitted by ferrets, a more recent popular house pet, are also considered. Although most zoonoses contracted from pets are relatively rare events, clinicians should be aware of any animal exposure, especially in immunocompromised hosts. Because of the diversity and the large size of the pet population, exposure to animals should be systematically ascertained when examining a patient. PMID- 1608687 TI - Tuberculous brain abscess in a three-year-old South Pacific Islander. PMID- 1608688 TI - Measles in mother-infant pairs. PMID- 1608689 TI - Mannan antigenemia during invasive candidiasis caused by Candida tropicalis. PMID- 1608690 TI - Interleukin 6 as early mediator in neonatal sepsis. PMID- 1608691 TI - Mucor peritonitis associated with acute peritoneal dialysis. PMID- 1608692 TI - Rectal bleeding caused by Campylobacter jejuni in a neonate. PMID- 1608693 TI - Histoplasmosis and perinatal human immunodeficiency virus. PMID- 1608694 TI - Tracheal diphtheria mimicking bacterial tracheitis. PMID- 1608695 TI - Prepatellar bursitis in an infant caused by group B Streptococcus. PMID- 1608697 TI - Pneumothorax and Pneumocystis pneumonia in an infant with acquired immunodeficiency syndrome. PMID- 1608696 TI - Immune response to nontypable Haemophilus influenzae after neonatal sepsis. PMID- 1608698 TI - Congenital anomalies resulting from maternal varicella at 25 1/2 weeks of gestation. PMID- 1608699 TI - Therapeutic considerations in congenital syphilis. PMID- 1608700 TI - Stool cultures in acute gastroenteritis. PMID- 1608701 TI - Examination of the relationship between the Myers-Briggs Type Indicator and empathetic response. AB - This study investigated the potential relationship between the Myers-Briggs Type Indicator and level of empathetic responding. Analyses indicated that the Thinking-Feeling scale was significantly associated with ratings of empathy for 49 graduate students in counselor education. Sex and graduate grade point average were also related significantly to empathic responding. Results are discussed in terms of their significance for research. PMID- 1608702 TI - Assessing cognitive domain levels of instructional materials. PMID- 1608703 TI - Colour of reading material and performance decrement. PMID- 1608704 TI - Imagery, concreteness, emotionality, and meaningfulness values of words: replication and extension. AB - We hypothesized that, contrary to prior investigations, when concrete and abstract words have similar meanings, correlations of rated emotionality with ratings of imagery, concreteness, and meaningfulness would be positive. 106 subjects rated 48 pairs of words, such as friend and friendship, that differ in only one morpheme. The words of these pairs all differed in concreteness but little in core meaning. Subjects rated the words on imagery, concreteness, emotionality, and meaningfulness. Correlations among all variables were positive and significant: .72 for imagery and emotionality, .71 imagery and meaningfulness, .87 imagery and concreteness, .41 emotionality and meaningfulness, .57 emotionality and concreteness, and .62 meaningfulness and concreteness. PMID- 1608705 TI - Societal influences on a thinner body size in children. AB - This study was designed to examine whether educational textbook illustrations portray children thinner since the turn of the century. 50 undergraduates each rated 54 third-grade text pictures (3 of boys and 3 of girls in each decade since 1900) on a thinness scale. Analysis indicated a significant trend in thinness for girls but not for boys. Concerns are raised about a connection between educational illustrations of children and eating disorders. PMID- 1608706 TI - A relapse-prevention program: effects of electromyographic training on high and low levels of state and trait anxiety. AB - This study involved 40 college subjects and investigated the effects of EMG training on high and low state- and trait-anxiety scores. At pretreatment assessment subjects were administered the Spielberger State-Trait Anxiety Inventory (1970). Subjects were treated with EMG training with an established treatment criterion of 3 microvolts. All subjects achieved the treatment criterion within six 20-min. training sessions. Daily homework practice sessions were recorded on behavioral data cards. Two-way analysis of variance indicated significant mean differences on both state and trait anxiety at the conclusion of treatment. Interactions were significant, with EMG affecting subjects high in anxiety differently from subjects low in anxiety. Multiple t tests indicated high state-anxiety scores dropped significantly more than high trait-anxiety scores. A 6-mo. follow-up assessment, employing biweekly mailing of behavioral data cards along with a protective contingency instituted by informing subjects they would be contacted by phone if the data cards were not received, showed that state anxiety scores remained significantly lower, while trait-anxiety scores returned to pretreatment levels. PMID- 1608707 TI - Relationship of attribution, expectancy, performance, and perceived success to change in examination preparation strategies. AB - The major purpose of this study was to investigate the relationship between change in strategies of preparation for examination and attributions, perceived success, and performance. Prior to each of three examinations in the course, 229 undergraduate students in introductory sociology and psychology were asked their expected score/grade. Change in strategies for preparation was assessed prior to Examinations 2 and 3. Subsequent to all three examinations students were assessed on attribution, satisfaction, and perceived success. Change per se and three of the strategies for change were related to performance, specific attributions, and perceived success. PMID- 1608708 TI - Sleep parameters of type A and B scoring college students. AB - 162 subjects, half of whom scored between 310 and 420 and half of whom scored between 184 and 256 on the Survey of Work Style questionnaire, participated in this study. The former group was defined as Type A scorers and the latter as Type B scorers. Type A scorers had more trouble falling asleep, had more nightmares, and spent less time asleep than did Type B scorers. However, there was no difference between the two groups in the amount of dream recall or on the morningness/eveningness continuum. PMID- 1608709 TI - Behavioral consultation with difficult to treat psychiatric patients. AB - Behavioral procedures have proven efficacious in the ward-wide treatment of psychiatric inpatients. These procedures are often recommended and administrated by behaviorally oriented staff who work as consultants. While numerous published reports show that behavioral consultation is effective for changing patients' targeted behavior, few data show whether it affects recidivism and other general indicators of patients' functioning. The present report describes group and case study data for 7 patients regarding the effects of behavioral consultation on frequency and duration of hospital admissions, distress upon readmission, proportion of time spent at regressive versus autonomous privilege levels, and other molar indices of patients' functioning. PMID- 1608710 TI - Increase in cutaneous temperature induced by hypnotic suggestion of pain. AB - Eight patients with atopic eczema and six healthy subjects were given hypnotic suggestion to feel pain in the upper part of the back and in one case on the palm. An average local increase in skin temperature of 0.6 degrees C (detected by thermovision) occurred under this condition. For some patients cutaneous pain threshold was increased before the experiment by means of repetitive hypnotic suggestion of analgesia. These subjects reported feeling no pain subjectively, but the local change in skin temperature was equal in both cases. The results suggest a central mechanism induced by measuring changes in pain threshold in the skin, which changes are independent of local changes in blood flow. PMID- 1608711 TI - Academic characteristics of self-identified illiterates. AB - The purpose was a descriptive account of the academic characteristics of 35 adults (22 men and 13 women) who perceived themselves as needing help in reading. Ages of participants ranged from 16 through 60 years. All had completed Grade 6, mean of Grade 11. Sixteen were functionally illiterate, that is, read below Grade 5. Twenty-seven were unemployed. The most common deficiencies found were in phonics, comprehension, and perception. All aspects of phonics, but especially the sounds of the short vowels, were a problem. Difficulties in perception were evident in reversals of letters and words, miscalling letters, and adding and omitting letters. Comprehension, the calling of words without knowing their meaning, was a major problem. Some individuals found it necessary to read aloud to understand. Others read so slowly they lost the meaning of a paragraph before they had finished it. Difficulty in remembering was perceived by some subjects as a factor in their lack of reading skill. It is hoped that by identifying these specific deficiencies in reading skills greater emphasis could be placed on them, and illiteracy could be prevented or at least reduced. PMID- 1608712 TI - Preserved implicit memory for lexical information in Alzheimer's disease. AB - Recent studies have suggested that there is a specific impairment of implicit memory for lexical priming in Alzheimer's Disease. However, there are problems in accepting data from the word-stem completion paradigm as evidence of pure implicit-memory performance. To assess whether Alzheimer's Disease patients are relatively impaired on implicit memory for lexical information an anagram solution task was adopted. A group of 16 early stage Alzheimer's Disease patients and a group of 16 normal elderly subjects were presented a list of 40 target words. Subsequent free recall was significantly poorer in the former group, but while both groups were significantly better at solving anagrams for words they had previously seen, there was no difference between the two groups in the amount of priming. The data are consistent with the view that previous reports of an implicit deficit in Alzheimer's Disease may not generalise to implicit tasks independent of explicit-memory performance. PMID- 1608713 TI - Incidence and severity of self-reported snoring in male and female college students. AB - The self-reported incidence and severity of snoring were assessed for a group of 749 college students. Although snoring was more frequently reported by the 356 men, these data did not support the speculation that snoring is a masculine secondary sexual characteristic. PMID- 1608714 TI - Academic learning problems and Rorschach indices: a Spanish replication. AB - This study compared the Rorschach responses of Spanish children who were and who were not judged by their teachers to be experiencing significant reading problems. With controls exacted on gender, social class, chronological age, and IQ, the responses of 15 pairs of subjects were examined; group differences in perceptual accuracy, self-concept, and reactivity were assessed. Consistent with American studies involving profiles of learning disabled and nonlearning disabled subjects, despite some differences being small, responses of children with reading problems were characterized by lower perceptual accuracy and lower self concept; inconsistent findings appeared on measures of reactivity. Empirical problems in conducting cross-cultural investigations with the Rorschach are discussed. PMID- 1608715 TI - Prediction of MMPI clinical scores from the Apperceptive Personality Test. AB - Eight independent scores from a new objective/projective personality test, the Apperceptive Personality Test (APT), were validated against eight clinical scores of the Minnesota Multiphasic Personality Inventory (MMPI). In parallel studies of 150 male and 150 female college volunteers given both tests, weighted combinations of the 8 APT measures significantly predicted MMPI raw scores in 15 of 16 analyses (Ma scores could not be predicted for men). Of 84 predicted zero order correlations between APT and MMPI measures, 50 (60%) were confirmed, 74% for women and 45% for men; however, the vast majority of these correlations were below .30. PMID- 1608716 TI - Severity of premenstrual symptoms in relation to medical/psychiatric problems and life experiences. AB - The Premenstrual Experience Assessment, a comprehensive questionnaire, was completed by 878 women who were currently having menstrual cycles. Their severity of premenstrual symptoms was studied in relation to demographic variables, gynecological problems, use of medications, psychiatric experience, life stressors, and duration of severity. 14 significant relationships were found. The findings are discussed both in terms of research and clinical practice. PMID- 1608717 TI - Why is life stress ignored in studies of 'stress' and athletic performance? AB - Investigations of relationships between stress and athletic performance and stress and outcomes outside of sport psychology have a parallel evolution. Each area has advanced from early attempts to find simple, strong relationships to current strategies for evaluating the influences of individual differences and situational factors on more elusive relationships. However, the most common conceptualizations of stress are very different in research on sport psychology and stress, and most studies of stress and athletic performance do not involve the influences of stress outside athletics. We propose that the approaches used by sports psychologists and stress researchers could be combined to evaluate more fully the relationships between stress and athletic performance. PMID- 1608718 TI - Field dependence/independence and learning condition: an exploratory study of style vs ability. AB - Recent reviews have concluded that field-independent individuals typically show learning equal or superior to that of field-dependent individuals. However, many studies supporting these conclusions have not capitalized fully on the stylistic strengths of field-dependent learners. Among 35 field-independent and 42 field dependent undergraduates, when grade-point average was controlled, no significant differences were found in scores on an examination following an audiotaped lecture. However, field-dependent learners significantly outperformed their field independent peers on follow-up quizzes when material was presented interactively, using examples that required social sensitivity for full appreciation. These results are discussed as supporting the importance of further study of the stylistic aspects of field dependence/independence and the narrowness of conceptualizations of individual differences when teaching. PMID- 1608719 TI - Frequency of day residue in dreams of young adults. AB - The percentage of dreams with day residue that could be identified by the dreamer, without free associating to the dream, was observed for a sample of 44 men and 44 women college students. The men identified day residue in 46.6% of their dreams and the women identified day residue in 48.9% of their dreams. The results were discussed in the context of Freud's idea that, while every dream likely has day residue, only some dreams have residue that can be identified without first free associating to the dream. PMID- 1608720 TI - Attenuating Necker cube depth reversals. AB - Rapid, apparent, to-and-fro (right-left) rotation of the Necker cube sharply reduced reversals in depth for 10 undergraduates. This finding was considered consistent with the satiation theory of Necker cube reversals. PMID- 1608722 TI - Effects of time of day, introversion and neuroticism on selectivity in memory and attention. AB - Two experiments examined the effects of time of day, introversion and neuroticism on selectivity in memory and attention. The first experiment showed that none of these factors interacted with task priority, which suggests that such variables do not produce the same changes in selectivity as do exogenous factors such as noise. In Exp. 2, colour names were read more quickly in the late afternoon than in the early morning, whereas patches of colour were named more quickly in the morning. Results from the Stroop interference condition showed that subjects classified as extraverts on the basis of Eysenck Personality Questionnaire scores were less susceptible to distraction than those scored as introverts, but the size of this effect was influenced both by time of day and by whether the subjects scored as stable or neurotic on the questionnaire. PMID- 1608721 TI - Resting cardiovascular activity and antisocial behavior in Essential and Reactive alcoholic men. AB - This study showed that 10 men identified as Essential alcoholics had significantly lower resting systolic and diastolic blood pressures and significantly higher scores on Latcham's measure of antisocial behavior than 11 Reactive alcoholics. For all alcoholics the antisocial measure was positively correlated with the total score on the Rudie-McGaughran questionnaire. Also, the antisocial measure was negatively correlated with diastolic blood pressure and heart rate. If lower resting cardiovascular activity were a psychophysiological indicator of more antisocial behavior, change on both variables could be associated with initiation and maintenance of alcoholic drinking by Essential alcoholic men. PMID- 1608723 TI - A normative sample using the Loong Computerized Tapping Program. AB - This article provides results of a comparison between the Halstead-Reitan tapper and a 1988 computerized tapping program by Loong. Care should be taken in using the computerized tapper in diagnosis or assessment. PMID- 1608724 TI - Concept of visual sensation in a theory of visual attention: a theoretical note. PMID- 1608725 TI - Does the type of eye motion determine whether induced motion is diminished or enhanced? PMID- 1608726 TI - Reliabilities, norms and factor structure of the Behavioral Dyscontrol Scale. AB - This is a report on the statistical properties of a research and clinical measure of cognitive and behavioral functioning, which has so far demonstrated utility among elderly persons. This instrument, the Behavioral Dyscontrol Scale, is adapted from Luria's approach to the assessment of frontal lobe dysfunction. The scale shows high internal consistency and very good interrater reliability. In a clinically stable, elderly population, test-retest reliability is high. Normative data are presented for three different samples: 47 young adults, 141 cognitively normal elderly persons, and our total elderly sample of 229. A principal components analysis yielded 3 factors consistent with Luria's theory. PMID- 1608728 TI - Correlates of self-perceived fitness. AB - This paper reports the associations between two global measures of self-perceived fitness and numerous objective fitness and fitness-related measures among 118 British men and women (mean age = 37.9 yr.). Self-perceived fitness, indicated on both a semantic scale of excellent through very poor (I) and an ordinal scale of 1 through 5 (II), was significantly correlated with most fitness and fitness related variables. For self-perceived fitness I and II, respectively, these included physical work capacity (rho = 0.48 and 0.51), percent body fat (rho = 0.27 and -0.39), grip strength (rho = 0.30 and 0.35), very hard leisure-time physical activity (rho = 0.47 and 0.35), and frequency of sweating (rho = 0.54 and 0.45). Stepwise regression analyses yielded Rs of 0.70 and 0.64 for self perceived fitness I and II, respectively. A significant correlate of self perceived fitness was self-perceived health (rho = 0.47), suggesting that people may perceive fitness and health in the same manner. The present data suggest the considerable scope for examining further how people interpret the concept of fitness. PMID- 1608727 TI - Comeditation: an exploratory study of pulse and respiration rates and anxiety. AB - To achieve deep relaxation in seriously ill persons, Tibetan medicine has employed a breathing process, known as "comeditation," which requires a caregiver to focus attention on the chest of the reclining patient while making a sound or number keyed to the patient's exhalation. This study investigated the relationship between state and trait anxiety and lowered respiratory rate, using the comeditation procedure. Ten subjects were assigned randomly to either a control or comeditation group. Anxiety was measured on the State-Trait Anxiety Inventory. Analysis indicated a decrease in State-Anxiety scores in the comeditation group, but no differences between groups in pulse and respiration rates or trait anxiety. Implications for theory and research are discussed. PMID- 1608729 TI - Physical and psychosocial benefits of modified judo practice for blind, mentally retarded children: a pilot study. AB - A modified form of judo training was practiced by a class of 7 blind, mentally retarded children with associated neuropsychiatric disturbances. The biweekly training program lasted for 6 months. Analysis indicated improvements in physical fitness, motor skills, and psychosocial attitude. The authors concluded that a modified form of judo can be used as a therapeutic, educational, and recreational tool for multiply handicapped children. PMID- 1608730 TI - Test-retest reliability of the Work Addiction Risk Test. PMID- 1608731 TI - Hand differences on a sensory test using tactual stimuli. AB - To examine hand differences in the sensory feeling of texture, 35 subjects made sensory evaluations with the left and the right hands to a tactile stimulus (sponge rubber) and also marked on a 5-point Likert scale 50 adjectives which represented various tactual feelings. Factor analyses, applied to the data of 35 subjects, showed that the left hand related more to a keen and sharp dimension while the right hand related more to a mild and soft dimension of the tactile stimulus. Possible relations of these hand differences in sensitivity to hemisphere functioning were discussed. PMID- 1608732 TI - Roll, pitch, longitudinal and yaw vection visually induced by optical flow in flight simulation conditions. AB - The present experiment was undertaken to study the effect of the addition of stimulation in the peripheral visual field on perceived self-motion (vection). The parameters were axes of motion, "Central + Peripheral" versus "Central vision, frequencies of sinusoidal motion (0.2 Hz to 1.0 Hz), and amplitudes. Vection generally increased with increased amplitudes and frequencies. In the "Central + Peripheral" condition, there was an interaction between frequencies and amplitudes. When stimuli were presented in "Central" vision only, vection was generally higher. It has been concluded that, for vection, the addition of visual stimulation in the periphery is more important at low sinusoidal frequencies and high amplitudes; at higher frequencies, this produces a decrease in vection probably attributable to an increase in object motion perception. PMID- 1608733 TI - Positive effects of subliminal stimulation on memory. AB - To assess the effect of subliminally embedded auditory material on short-term recall, 60 volunteer subjects undertook a face-name-occupation memory test before and after a 15-min. intervention. They were randomly assigned into three groups (a control group and two experimental groups) and allocated to one of the following conditions: (1) no sound, (2) supraliminal presentation of relaxing music, and (3) subliminal presentation of memory-improvement affirmations embedded in relaxing music. After intervention, only the subliminal group significantly improved their performance on recall of names. PMID- 1608734 TI - Subliminal psychodynamic activation: updated comprehensive list of experimental results and comments on previous lists. AB - A comprehensive list of results from visual subliminal psychodynamic activation experiments is presented. This list includes results reported since the publication of the last comprehensive list by Weinberger and Hardaway in 1990 and several results not found on that list. On the present list, SPA results are categorized according to criteria that we contend are more objective than those used previously. In contrast to conclusions drawn from previous lists prepared by Silverman in 1980 and 1983, by Weinberger and Hardaway in 1990, and by Weinberger and Silverman in 1987, the present list indicates that the results of a majority of experiments do not clearly support hypotheses tested by the subliminal psychodynamic activation method. Aspects of Hardaway's meta-analyses from 1987 and 1990 for major areas of research on subliminal psychodynamic activation are discussed in terms of suggestions for further research. PMID- 1608735 TI - Habitual participation in exercise and personality. AB - Two personality characteristics of 21 habitually exercising and 14 nonexercising college students were compared by using the Eysenck Personality Inventory. The former scored higher on Extraversion than the latter. Both groups of men (ns = 9 and 6), as well as 12 exercising women, scored lower on Neuroticism than 8 nonexercising women. PMID- 1608737 TI - Clinical teaching in nursing education. PMID- 1608736 TI - Perceptual strategies of isolation in obsessive-compulsive personality disorder. AB - Recent findings have shown that the Defense Mechanism Test, a serial tachistoscopic technique developed inside the percept-genetic frame of reference, discriminates neurotics from normals, neurotics from schizophrenic outpatients, and subjects with histrionic personality disorder from controls. The present research addresses another major class of Axis II pathology, comparing on the Defense Mechanism Test a group with a psychometric diagnosis of obsessive compulsive personality disorder (n = 26) with a matched sample of noncompulsive controls. As predicted, several variants of isolation were significantly more characteristic of the compulsive group. Intellectualization, disappearance of the whole structure, whitening of the hero, and lack of recognition of the threat were the variants of isolation with the best discriminative properties. Codings of reaction formation were not linked with compulsive personality, which is congruent with the recent observation of their correspondence to the histrionic personality disorder. The findings are presented in the context of the percept genetic literature on obsessive-compulsive defensive strategies. PMID- 1608738 TI - Nursing data review. 1992. PMID- 1608739 TI - Associate degree nursing programs accredited by the NLN 1992-93. PMID- 1608740 TI - Scholarships and loans for nursing education. 1992-1993. PMID- 1608741 TI - [Physicians' heroic efforts with children affected by alcohol]. PMID- 1608742 TI - [Alcohol problems in the health services--secondary preventive strategies]. AB - An effective secondary preventive programme to deal with alcohol problems presupposes adequate knowledge of the population's drinking habits, the problems accompanying alcohol abuse, the manner in which the health services encounter the problem drinker, professional expertise in secondary prevention, and the methods shown by research to be effective. The knowledge does exist, and it only remains to implement a unified programme for secondary preventive measures within the health services at a local or national level. PMID- 1608744 TI - [Early detection and early intervention--district physician's role]. AB - In patients with established alcohol dependence or advanced alcohol abuse, medical treatment yields fairly poor results; and although early intervention may be effective in impeding the progression of incipient abuse, the problem must be brought to light in good time and the approach to intervention must be effective and easy to apply in the primary care context. The district medical officer is ideally placed to identify and deal with early alcohol problems in patients. PMID- 1608743 TI - [Biological alcohol markers. Genetic markers for familial alcoholism and markers for the detection of harmful alcohol consumption]. AB - Existing biological markers of alcoholism and excessive alcohol consumption are of poor sensitivity and specificity, and new, improved markers are needed. Owing to the genetic contribution to the development of alcoholism, as demonstrated in family and adoption studies, a search has been initiated for 'preventive' or genetic markers. In addition, other new biochemical markers have been introduced, and results so far obtained with CDT (carbohydrate deficient transferrin) in the detection of alcoholics have been promising. However, the clinical and scientific implications of these new markers need to be elucidated in greater detail. PMID- 1608745 TI - [The treatment of drunk drivers]. AB - Conviction for a drunk driving offence entails automatic disqualification. A doctor's certificate recommending the approval or disapproval of driver's license renewal would seem to be a crucial prerequisite in the rehabilitation of an offender. Together with educational programmes, fines and imprisonment, such actions vis-a-vis driving licenses would seem to be feasible adjuncts to rehabilitation, though their implementation would naturally need to be varied according to the severity of alcohol dependence and the risk of recurrent drunk driving. PMID- 1608746 TI - [Support to pregnant women with dependence problems]. PMID- 1608747 TI - [Acute alcoholic intoxication--risk of complications]. AB - Alcohol intoxication is the commonest cause of unconsciousness among patients admitted to hospital. Studies have shown that, of all acute admissions to medical wards, approximately 20 per cent are patients who are intoxicated or have alcohol related damage. A study cited in the article showed patients in deep stupor generally to have a blood alcohol concentration above 70 mmol/l, and to be at increased risk of respiratory complications and aspiration of regurgitated stomach content. In cases of severe alcohol intoxication, treatment includes the following: freeing of the airways, perhaps combined with respiratory support; tracheobronchial lavage and aspiration, followed by antibiotic treatment; liberal parenteral thiamine administration; cramp, hypoglycaemia and muscle damage may require special measures; in the acute stage, cardiac arrhythmia usually normalizes without special antiarrhythmic treatment. PMID- 1608748 TI - [Multiple injuries and quality control]. AB - A prospective registration was carried out of all patients with multiple injuries who were admitted to hospital in 1990 during the first 24 hours after the accident. The total number was 441, and included 47 patients with penetrating injuries. Such patients constituted 5 per cent of a total of 9,000 admitted patients, and 19 per cent of a total of 2,266 injured persons. The injuries were scored using the Trauma Score and Injury Severity Score (ISS) and the probability for survival was calculated by the TRISS method. 148 patients were seriously injured, having an Injury Severity Score 16 or more. Traffic accidents were most common, and were the cause of injury in more than 50 per cent of the patients. 15 per cent of the patients with such injuries were under the influence of alcohol and 5 per cent were drug abusers. The percentage under the influence of alcohol was three times as high, however, among patients injured by violence. Median ISS was 26 for the whole series, and 41 for the 41 patients who died. Mortality was significantly higher in patients older than 54 years of age than among younger patients. No patients were reduced to a vegetative state, but 13 per cent of the surviving patients were considerably disabled. Among the 41 patients who died the main cause of death was haemorrhage in 17, and airway obstruction in five. Estimation of probability of survival showed that the mortality in this series compared well with the mortality in larger series of injured persons in America. None the less, improvement is still feasible. PMID- 1608749 TI - [Functional electric stimulation of the phrenic nerve and its clinical significance]. AB - The peripheral parts of the phrenic nerve are healthy in some of the patients who require permanent or intermittent care in a respirator owing to reduced respiratory function of central aetiology. In such cases, continual care in a mechanical respirator can be avoided, and diaphragm function maintained by means of functional electrical stimulation (FES) of the phrenic nerve with carefully controlled electrical impulses. The method is suitable for use in certain cases of quadriplegia, or in patients with sleep apnoea. Experience with the method has shown that health care costs can be reduced and the patients' quality of life improved. In some cases, the patient may even regain partial work capacity. PMID- 1608750 TI - M3: managing stress. Part (II). A strategy for coping. PMID- 1608751 TI - Dangerous kicks. PMID- 1608752 TI - Cheap labour? PMID- 1608753 TI - Research priorities. PMID- 1608754 TI - Restless spirits. PMID- 1608755 TI - Listening to carers. PMID- 1608756 TI - Acute confusion. PMID- 1608757 TI - Qualified trainees. PMID- 1608758 TI - Public prejudice. PMID- 1608759 TI - The courage of Alice. PMID- 1608760 TI - Reducing hypertension. PMID- 1608761 TI - A helping hand. Interview by Daloni Carlisle. PMID- 1608762 TI - The power of words. PMID- 1608763 TI - Educating parents. PMID- 1608764 TI - Perineal trauma. PMID- 1608765 TI - Careers focus. Continent advice. PMID- 1608766 TI - Chinese fail to seek help for HIV. PMID- 1608767 TI - Nursing Times open learning programme. M4: assertiveness. Part (II): How assertive are you? [continuing education credit]. PMID- 1608768 TI - Cheers! PMID- 1608769 TI - Professional services. PMID- 1608770 TI - Positive reaction. PMID- 1608771 TI - Morale imperative. Interview by Linda Davidson. PMID- 1608772 TI - Smacks of ignorance. PMID- 1608773 TI - Burning needs. PMID- 1608774 TI - Nursing the soul. PMID- 1608775 TI - Depression. The story of the blues. PMID- 1608776 TI - Depression. The perpetual shadow. PMID- 1608777 TI - Depression. On the frontline. PMID- 1608778 TI - CATS: your questions answered. PMID- 1608779 TI - Experience counts. PMID- 1608780 TI - Sickle cell disease. Adaptation to adversity. PMID- 1608781 TI - Making sense of accidental exposure to blood and body fluids. PMID- 1608782 TI - Excellence in the community. PMID- 1608783 TI - Nursing narratives. Careless whispers. PMID- 1608784 TI - Nursing narratives. Space to speak. PMID- 1608785 TI - Screen test. PMID- 1608786 TI - Planning on a PC. PMID- 1608787 TI - Professional development module. P8: Ethics and care. Part (i): Making judgements. PMID- 1608788 TI - Where is the named nurse for all? PMID- 1608789 TI - AIDS-Forum wide ranging. PMID- 1608790 TI - Shocking prospects. PMID- 1608791 TI - Myth of madness. Interview by Ian McMillan. PMID- 1608793 TI - Hostess folly? PMID- 1608792 TI - Vitamin controversy. PMID- 1608794 TI - Last chance for midwives. PMID- 1608795 TI - Management: the indomitable Mr. Pink. Whistle-blowers. Interview by Toni Turner. PMID- 1608796 TI - Management: a clause for alarm? Whistle-blowers. PMID- 1608797 TI - Management: self-imposed silence. Whistle-blowers. PMID- 1608799 TI - Bath rights. Midwifery. PMID- 1608798 TI - To the water born. Midwifery. PMID- 1608800 TI - Breathtaking experience. Care study. PMID- 1608801 TI - Prisoners of the system. PMID- 1608802 TI - Patient's progress. PMID- 1608803 TI - Reviewing attitudes to self-medication. PMID- 1608805 TI - Systems of life. Muscle. 2. PMID- 1608804 TI - Gearing up to work in a secure unit. PMID- 1608806 TI - Infection control. Child's play. PMID- 1608807 TI - Infection control. Why not wash? PMID- 1608808 TI - Infection control. A breath of hope. PMID- 1608809 TI - P8: ethics and care. Part (II): The duty to care. PMID- 1608811 TI - Changing the code. PMID- 1608810 TI - Blighted childhood. PMID- 1608812 TI - Changing the code. PMID- 1608813 TI - Arresting facts. PMID- 1608814 TI - Pale is beautiful. PMID- 1608815 TI - Safe in the sun? PMID- 1608817 TI - Positively not on. PMID- 1608816 TI - Letter to my mentor. PMID- 1608818 TI - A painful experience. PMID- 1608819 TI - Keeping a high profile. PMID- 1608820 TI - Taxing assessments. PMID- 1608821 TI - A haven in hell. PMID- 1608822 TI - Heretical notions? PMID- 1608823 TI - The art of positive drinking. PMID- 1608824 TI - Antidepressants. PMID- 1608825 TI - The reality of rape. PMID- 1608826 TI - Facing facts. PMID- 1608827 TI - Triage: setting priorities for health care. AB - The concept of triage is central to the allocation of healthcare resources. As demands for health care increase, medical technologies and providers become more expensive and more scarce. Triage decisions occur at all levels in the distribution of resources. It is essential to explore the concept of triage and some of the underlying ethical principles for triage decision-making from the perspective of the discipline of nursing. Examining how definitions of triage apply to practice will enable nurses to participate in reform strategies for the healthcare system. PMID- 1608828 TI - One year later: using role theory to evaluate a new delivery system. AB - This is the second part of a two-part article that presents findings from a staff nurse survey one year after the implementation of primary nursing on four medical and surgical pilot units in a tertiary teaching hospital. The introduction of primary nursing was one phase of a project to develop theory-based nursing practice within the institution. The researchers hoped that obtaining the staff nurse perspective on the change to primary nursing would provide evaluative information and suggestions to provide additional support in the project. Role theory (Hardy, 1978) provides the theoretical framework for this study. While the previous article discussed issues related to the change process, this article focuses on evaluation of role transitions. PMID- 1608830 TI - Writing nursing's story. PMID- 1608829 TI - Assessment and intervention for certainty and uncertainty. AB - Research suggests that high degrees of uncertainty and absolute certainty can be very stressful for nursing's clients. Yet, research also suggests that a moderate degree of unexpectedness, unpredictability, and uncertainty may actually produce positive effects--pleasure, hope, information pattern search, and a sense of well being. The author discusses the research related to psychological certainty and uncertainty, provides suggestions for assessing clients' degree of certainty and uncertainty, and delineates interventions for dealing with detrimental levels of certainty and uncertainty. Precautions for instituting interventions are also stressed. PMID- 1608831 TI - The "forced choice item" theory of nursing. PMID- 1608832 TI - Promoting health by promoting comfort. AB - While comfort is a concept frequently addressed in the nursing literature, few have adequately addressed this concept as a central patient objective. At present, our literature focuses more on comfort as a nursing action than on comfort as an individualized patient goal. Comfort may be more likely to be the driving force for patients obtaining healthcare services than health itself. This patient need, coupled with nursing interventions to assist them in identifying and implementing constructive ways of promoting their own comfort needs, will help to achieve an optimal state of health. PMID- 1608833 TI - Is nursing's image a deterrent to recruiting men into the profession? Male high school students respond. AB - The extremely small number of men choosing the nursing profession as a career, coupled with the continuing shortage of nurses, prompted an investigation of male high school students' opinions about nursing. Kohler and Edwards' Career Questionnaire was administered to 126 male high school students representing grades 9-12 from three area public schools. Findings show that although the majority of subjects have a positive perception of nurses and nursing, the vast majority are not planning on entering the profession. Analysis of subjects' beliefs about nurses' financial status offers a possible explanation. PMID- 1608834 TI - Searching. PMID- 1608835 TI - Radiation exposure compensation program announced. PMID- 1608836 TI - AIDS newsletters provide up-to-date information. PMID- 1608837 TI - Multiple systems organ failure in the patient with cancer. Part I: pathophysiologic perspectives. AB - Multiple systems organ failure (MSOF), a phenomenon observed in many critically ill patients with cancer, is the progressive failure of two or more organ systems, which results from nonspecific systemic responses to abnormal intravascular inflammation. It is triggered by a number of cellular, humoral, and biochemical mediators. MSOF in the patient with cancer has been associated with aggressive antineoplastic treatment regimens, which often cause profound alterations in the body's normal homeostatic balance. Part I of this two-part review will discuss the pathophysiology of MSOF, including epidemiology, prognosis, and clinical manifestations. Key relational factors, as well as current and future therapeutic considerations, also will be described. PMID- 1608838 TI - Multiple systems organ failure in the patient with cancer. Part II: nursing implications. AB - Because of the expansion of aggressive therapeutic modalities, multiple systems organ failure (MSOF)--a sequential deterioration in vital organ function, is being diagnosed with increasing frequency in today's cancer population. The high mortality rate associated with this complex syndrome demands that oncology nurses become knowledgeable about its potential for development. Part II of this two part review focuses on the collaborative role of the nurse in the recognition and prevention of MSOF. Key criteria for determining systemic failure are described, and pertinent oncologic risk factors are identified. A clinical evaluation guideline outlines important assessment criteria, laboratory studies, and nursing priorities for each system. PMID- 1608839 TI - Evolving a blueprint for certification: the responsibilities and knowledge comprising American professional oncology nursing practice. AB - Ensuring adequate content validity of a certification examination is a major concern in the development and administration of a test. To establish content validity of the Oncology Nursing Certification Corporation (ONCC) certification exam, a job analysis study was conducted to provide empirical data about the responsibilities and knowledge areas required for practice at the level of the newly certified oncology nurse. The study involved The Profession of Oncology Nursing: An Inventory of Responsibilities and Knowledge (IRKPON), a questionnaire that was developed based on a review of the literature, professional practice information, interviews with oncology nurses, the original ONCC certification exam table of specifications, and evaluations undertaken by two advisory committees. The IRKPON consisted of three parts: 56 responsibilities clustered into eight job dimensions, 217 knowledge areas grouped into seven knowledge dimensions, and demographic information. The IRKPON was sent to a stratified random sample of 3,000 oncology nurses in the United States, who were asked to rate both the responsibilities and knowledge areas by level of importance. The 1,297 (43%) responding nurses rated 45 of 56 responsibilities (80.4%) as "very important" and 8 of 56 responsibilities (14.3%) as "extremely important"; they also rated 163 of 217 knowledge areas (75.1%) as "very important" and 41 of 217 knowledge areas (18.9%) as "extremely important." These findings identified the specific responsibilities most important to the oncology nurse role at the level of the newly certified nurse, as well as the knowledge areas necessary for competent performance. Subsequent ONCC certification examinations were modified; the test blueprint that guides the construction of the examination was revised, and the passing score was adjusted. PMID- 1608840 TI - Support and caring: exploring the concepts. AB - In their article "Dimensions of the Supportive Role of the Nurse in Palliative Care" (ONF 17:87-94, 1990), the authors used a grounded-theory approach based on the actual experiences of an expert nurse in supportive care. In this article, the authors relate their concepts of support to existing nursing theory and to previous clinical research in both support and caring. Justification for the dimensions of the model was found in the nursing literature. However, distinguishing support and caring as concepts was difficult. PMID- 1608842 TI - Cancer nursing education in the community hospital: principles and practice. AB - Cancer nursing content is conspicuously absent from the curricula of basic nursing education programs. Therefore, it becomes the responsibility of employing institutions to provide graduate nurses with a comprehensive nursing education that will ensure quality patient care; this may be accomplished through in-house or external continuing education programs. In 1987, the Educational Steering Committee for Cancer Care at The Washington Hospital was established to meet this need. Since its inception, the committee has developed, implemented, and evaluated four oncology core modules. Because patients with cancer are cared for throughout the institution, almost every nurse on the staff will, at some point in their career, care for a patient and family experiencing cancer. Therefore, nurses from many clinical settings are required to participate in the oncology core modules. At the time that this manuscript was published, 134 nurses had participated in at least one of the modules. Nurses who participate in the modules are awarded Pennsylvania Nurses Association contact hours. PMID- 1608841 TI - Identifying the needs of home caregivers of patients with cancer. AB - Increasing numbers of patients with cancer are being cared for by home caregivers. The primary purpose of this methodologic, correlational study was to identify, categorize, and assess the importance of needs expressed by 492 home caregivers and to determine how well these needs were satisfied. Caregivers surveyed were selected from the records of two nonprofit community cancer agencies and two hospital outpatient oncology clinics in the Midwest. These individuals were identified by at-home patients with cancer as unpaid people who helped with physical care or coping with the disease process. Caregiver characteristics and patient activity were examined to determine their relationships to caregiver needs, and needs were examined over time. The 90-item Home Caregiver Need Survey used in this study was developed by the author in 1989 and demonstrated internal consistency, reliability, and construct validity. Using factor analysis, six need categories were identified: psychological, informational, patient care, personal, spiritual, and household. Caregivers' greatest needs were informational and psychological. Significant correlations between certain caregiver characteristics and caregiver needs and between caregiver needs and patients' activity levels were found. Both the importance and satisfying of needs changed over time. Findings indicate the urgent need for nurses, who usually provide support for caregivers, to establish specific programs and services to meet the identified and unmet informational and psychological needs of caregivers of at-home patients with cancer. Frequent reassessment of caregiver needs seems to be indicated. PMID- 1608843 TI - Early and late radiation-induced skin alterations. Part I: Mechanisms of skin changes. AB - Early and late radiation-induced skin changes have been a concern of health professionals in radiation oncology since the early use of radiation to treat disease. Although the elicited skin reactions from solar exposure and ionizing radiation may appear to be similar, mechanisms of tissue injury are different. The time of onset, the duration, and the intensity of side effects related to radiation therapy are influenced by site of radiation field, time-dose-volume relationship, radiosensitivity of tissues in the skin, type and energy of radiation, nutritional status of the patient, adherence to skin management recommendations, and innate individual differences among patients. The effects of skin irradiation can be categorized as early and late reactions. When combined with radiation therapy, some chemotherapy agents as well as hyperthermia can enhance skin reactions. PMID- 1608844 TI - Documentation of care in an oncology outpatient setting. AB - Finding time to perform thorough documentation in a busy oncology outpatient setting is an increasingly difficult task. This article describes the development of a new documentation system designed for an oncology outpatient unit. The system consists of a set of documentation tools that are specific for the type of patient visit, an initial assessment form, and guidelines for using the forms. The system was developed to reduce the amount of nursing time spent on documentation and to improve the quality of the documentation. Evaluation of the system indicated that the forms decreased charting time by 50%. Suggestions for modifying and revising the tools are included. This system could be adapted for use in any ambulatory oncology setting. PMID- 1608845 TI - Early detection reduces risk of vulvar cancer. PMID- 1608846 TI - Adult cancer camp offers fun and inspires hope. PMID- 1608847 TI - Low-income program increases mammography compliance. PMID- 1608849 TI - Population pharmacokinetics of gentamicin in neonates using a nonlinear, mixed effects model. AB - The population pharmacokinetics of gentamicin in neonates was determined using a nonlinear, mixed-effects model (NONMEM). The final regression equations derived to estimate clearance (Cl) and volume of distribution (Vd) were Cl = 0.120 * (WT/2.4)1.36 L/hr and Vd = 0.429 * (WT) L. The interindividual variability (% CV) for clearance was 26.2% and for volume of distribution 15.9%. Intraindividual variability was 11.0%. In a separate group of 30 neonates, the predictive ability of the NONMEM-generated population variables was compared to the predictions from a standard two-stage population analysis. The trough concentrations predicted using NONMEM-generated parameters were significantly less biased and more precise; there were no significant differences between the methods in predicting peaks. NONMEM is a useful tool for determining population pharmacokinetics and appears to be consistent across populations using routine clinical data and limited observation. PMID- 1608848 TI - Oral nifedipine pharmacokinetics in pregnancy-induced hypertension. AB - The pharmacokinetics of oral nifedipine were studied in 15 women with pregnancy induced hypertension in the third trimester of pregnancy to determine if the drug's disposition was different from that in nonpregnant patients. Peak serum concentrations of 38.6 +/- 18 ng/ml occurred at approximately 40 minutes after ingestion of nifedipine 10 mg. The terminal elimination half-life (mean 1.3 +/- 0.5 hrs) was shorter than that reported for normotensive volunteers and nonpregnant hypertensives after oral dosing. Mean +/- SD apparent elimination clearance of 2.0 +/- 0.8 L/hr/kg was more rapid than that in healthy volunteers (mean 0.49 +/- 0.09 L/hr/kg). Random serum concentrations were progressively higher in patients receiving larger daily doses. Nifedipine was detected in samples of fetal cord blood and amniotic fluid at concentrations approximately 93% and 53% those of simultaneous maternal vein samples, respectively. The findings indicate that nifedipine may achieve greater antihypertensive efficacy in pregnant women if administered at shorter intervals. PMID- 1608850 TI - The effect of low-dose phenytoin on high-density lipoprotein cholesterol. AB - We examined whether low doses of phenytoin, which should be associated with few dose-related side effects, may increase the levels of high-density lipoprotein (HDL) cholesterol. Of 35 healthy adult men who consented to participate, 31 completed the study. They took no medications and consumed no alcohol during the study. We used a three-arm, parallel, prospective, randomized, double-blind research design. Subjects took a single-blind placebo capsule once daily at bedtime for 2 weeks and then were randomly assigned to receive identical appearing capsules containing 30 mg or 100 mg of phenytoin or placebo, once daily at bedtime for 4 weeks. The HDL cholesterol and HDL subfractions were determined from 12-hour fasting blood samples obtained at the beginning and end of the single-blind period and at the end of the third and fourth weeks of the double blind period. Mean differences between baseline and posttreatment HDL cholesterol levels with placebo, 30 mg phenytoin, and 100 mg phenytoin were 0.010 mmol/L (0.4 mg/dl), 0.005 mmol/L (0.2 mg/dl), and 0.096 mmol/L (3.7 mg/dl), respectively (p = 0.2947); baseline and posttreatment HDL2 and HDL3 levels were not different among the groups. Total cholesterol levels were significantly higher in subjects taking phenytoin 100 mg than in those taking phenytoin 30 mg or placebo. The results suggest that phenytoin in dosages of up to 100 mg daily for 4 weeks has no substantial effect on HDL cholesterol or HDL subfractions. PMID- 1608851 TI - Relationship between serum quinidine concentration and quinidine dosage. AB - This retrospective study was designed to identify and assess which patient specific factors affect the relationship between the steady-state trough serum quinidine concentration (SQC) measured by fluorescence polarization immunoassay and quinidine dosage. Data were obtained from 100 hospitalized patients (72 males, 28 females) receiving quinidine for atrial or ventricular arrhythmias, or both, between ages 24 and 85 years (mean age 63 yrs). Age, lean body weight, creatinine clearance (ClCr), and sex were statistically significant factors affecting this relationship; ejection fraction, total body weight, smoking history, alcohol history, recent myocardial infarction, recent surgery, elevated liver function tests, and sampling time were not statistically significant. The ClCr alone provided the most additional information in predicting SQC, and ClCr and weight provided the most additional information in predicting dosage. Currently in clinical practice, quinidine dosage adjustments are not routinely recommended for patients with renal insufficiency. These data suggest that the calculated ClCr is important in predicting both SQC and dosage when a nonspecific quinidine assay is used. This dosing model must be evaluated prospectively. PMID- 1608852 TI - A simple method to estimate the initial dose of gentamicin. AB - A simple equation to estimate the initial dosing interval of gentamicin was compared with the "rule of eights" equation in 81 adult patients with stable renal function. The Sawchuk-Zaske method was employed as the standard with which dosing intervals estimated by the simple equation and the rule of eights method were compared. The actual mean peak gentamicin concentration was not significantly different from that predicted by the Sawchuk-Zaske method. The actual mean trough concentration was significantly higher than the predicted concentration, but trough concentrations within the usual therapeutic range of 0.5-2 microgram/ml were achieved in more than 90% of patients. The mean dosing interval calculated by Sawchuk-Zaske was not significantly different from that calculated by the equation, but was longer than the one calculated by the rule of eights. A peak gentamicin concentration within the usual therapeutic range was generally achieved with a total daily dose of 3-5 mg/kg of actual body weight. Until gentamicin concentrations are known, an easily remembered equation can be used to estimate the initial dosing interval for gentamicin. When used together with a standard total daily dose of 3-5 mg/kg total body weight, usual therapeutic concentrations are achieved in the majority of patients. PMID- 1608853 TI - Mathematic modeling of drug disposition and postdialysis rebound in patients requiring hemodialysis. AB - We developed a model to describe intradialysis and postdialysis serum concentration changes and, in concert with nonlinear regression, to estimate drug removal during hemodialysis. A Lotus-based computer simulation program was developed that describes drug disposition in this therapy. The hemodialysis removal rate constant and beta were two important factors identified that influence postdialysis rebound. Also, a nonlinear regression routine using PCNONLIN was developed that enables simultaneous fitting of predialysis, intradialysis, and postdialysis drug concentration data. Data from four patients who received intravenous sulbactam were analyzed using this model. The mean measured amount of sulbactam removed by hemodialysis was 446 +/- 32 mg versus predicted amounts of 456 +/- 92 mg from model estimates, and 449 +/- 33 mg when dialysate recovery of drug was included in the input. This program will be useful in characterizing pharmacokinetic constants and predicting hemodialysis drug removal. PMID- 1608854 TI - Liver disease associated with diclofenac, naproxen, and piroxicam. AB - Based on information derived from computers used by general practitioners in the United Kingdom, we identified all patients with any recorded diagnosis of a liver disorder within 90 days of a prior prescription for diclofenac, naproxen, or piroxicam, three nonsteroidal antiinflammatory drugs (NSAIDs). The follow-up cohort consisted of 102,644 persons who used one or more of these drugs. A case history was requested from the physician to provide a description of the liver disorder and its relation to NSAID exposure. One case of clinically important liver disease was likely to have been caused by a study drug and another appeared to be caused by use of numerous NSAIDs. In 10 additional patients a causal connection between a study NSAID and the liver disorder seemed unlikely but could not be fully ruled out. We conclude that serious liver disease caused by diclofenac, naproxen, or piroxicam appears to be uncommon. PMID- 1608855 TI - Intensive surveillance of midazolam use in hospitalized patients and the occurrence of cardiorespiratory arrest. AB - Midazolam, a benzodiazepine used extensively as a sedative and a hypnotic for patients undergoing inpatient and outpatient medical procedures, has been associated with several side effects, the most serious of which are cardiac and respiratory arrest. We studied the use of midazolam and its association with cardiac and respiratory arrest among hospital patients at our institution. From 1988 through 1990 we identified 5439 patients exposed to midazolam, representing 8% of all patients admitted; 3031 (55.7%) received midazolam while not on mechanical ventilation. In the majority of patients the drug was given as a one time dose, and the total dose was less than or equal to 5 mg in more than 70%. Three patients (0.099%) experienced respiratory arrest. All three events occurred within 2 hours after the last dose of midazolam had been given. All patients were elderly and all survived. The rate of respiratory arrest appears low at our institution and was associated with high doses of midazolam, concurrent use of opiates, and use in elderly patients. PMID- 1608857 TI - A guide for assessing pharmacoepidemiologic studies. AB - Pharmacoepidemiologic studies are appearing with increasing frequency in clinical journals, describing associations between commonly used drugs and rare adverse clinical events. Before practitioners accept conclusions of causality and alter patterns of practice based on these studies, they should perform two steps: apply a critical appraisal filter to the evidence to determine whether the claims are justified, and explore the consequences of not using a drug associated with an undesired effect. This guide for critically appraising the literature on adverse drug effects emphasizes the need to evaluate the potential biases associated with studies that use nonexperimental designs. PMID- 1608856 TI - Therapeutic frontiers in Alzheimer's disease. AB - Alzheimer's disease (AD), the most common type of primary degenerative dementia, is the leading cause of cognitive impairment in the geriatric population. It is a devastating illness, both to the patients and the families involved. Although much research continues to be conducted, the etiology and effective treatment for the disease remain to be found. One of the primary hypotheses of the disease is that the cognitive decline of AD involves the loss of related cholinergic neurons. Although the cholinergic theory is still valid, efforts aimed at increasing levels of acetylcholine have yielded disappointing results. Currently, in the United States, several drugs are in various stages of development for the treatment of AD. The mechanisms of these agents include cerebral protectants, enhancers of neuronal signal amplification, tonic stimulation, and nerve growth factors. Other avenues being investigated include the development of novel drug delivery systems to enhance CNS concentrations of therapeutic agents. PMID- 1608860 TI - Health care reform: the time is now. PMID- 1608859 TI - Infrequent RAS oncogene mutations in human prostate cancer. AB - The RAS gene family includes three functional genes, H-RAS, K-RAS, and N-RAS, which have been most widely studied in human tumors. Point mutations most commonly occurring at codons 12, 13, or 61 of these genes allow the RAS protooncogene to be converted to a RAS oncogene. A variety of human tumors have been studied for RAS mutations to date, however, conflicting data has been reported regarding prostate cancer. Cell line studies and two American studies of clinical material have found a low incidence of RAS mutation in prostate cancer. The few mutations found were predominantly in the H-RAS gene. Conversely, a recent study of Japanese occult autopsy specimens found an approximate 25% incidence of K-RAS mutations. In this current study, DNA was extracted from 24 archival paraffin-embedded, formalin-fixed radical prostatectomy specimens. Twenty-one of the 24 cases had pathologic stage C disease, and paraffin blocks were selected having the most concentrated area of neoplasm. Twelve, seven, and five cases demonstrated moderate, well and poorly differentiated histologic grade respectively. Polymerase chain reaction (PCR) was used to amplify the K-RAS, N RAS, and H-RAS 12, 13, 61 codons of these specimens and mutations were detected with mutation-specific oligonucleotide probe hybridization of southern and slot blots. No definite point mutations were detected. PCR's and hybridizations were performed three separate times by three investigators to confirm these results. PCR-generated mutation-specific positive controls and known negative controls were used and found to be important to interpret oligonucleotide hybridization assays. RAS gene mutations appear to be infrequent in clinical prostate carcinomas in American males. PMID- 1608858 TI - Prolonged hemodialysis in methanol intoxication. AB - Methanol poisoning may be treated conservatively by inducing a diuresis and administering ethanol to halt the metabolism of methanol to more toxic metabolites. In severe intoxications, hemodialysis may be necessary to remove the toxins and limit the metabolic disturbances. The duration of dialysis needed to achieve this is unclear. A case report of a severe methanol poisoning is reported which required 21 hours of hemodialysis to bring the serum methanol levels down to a nontoxic level. PMID- 1608861 TI - The influence of age, sex, and initial fit on bony ingrowth stabilization with the AML femoral component in primary THA. AB - A radiographic review of 178 consecutive primary total hip arthroplasties using the AML femoral component with a mean follow up of 40.1 months identified 92.3% to be stabilized by bony ingrowth and 7.7% by fibrous tissue. None were classified as loose. The quality of fit in the isthmus and calcar regions was identified as an important factor in achieving bony ingrowth stabilization. Bony ingrowth was achieved in all age groups with equal frequency. No relationship between sex and the type of stabilization was identified. A clinical correlation utilizing a subset of patients with identical prosthetic components identified equivalent clinical results across all age groups. Thirty-four percent of patients experienced some residual thigh pain. No statistically significant relationship between the presence of thigh pain and the type of femoral component stabilization (bony vs fibrous) could be identified. Ninety-eight percent of patients expressed unconditional satisfaction with their hip replacements. PMID- 1608862 TI - The risk of injury to the axillary nerve, artery, and vein from proximal locking screws of humeral intramedullary nails. AB - An elderly female cadaver fore-quarter amputation was dissected, and a custom straight intramedullary nail with a 55 degrees oblique downward lateral to medial proximal screw was inserted with a trocar protruding beyond the medial cortex of the humeral surgical neck. The main trunk of the axillary nerve was found to be at risk with any penetration from anterior to posterior and any screw penetration beyond the medial cortex with internal rotation. The axillary artery and vein were at risk with penetration of over 3 cm by a drill point or screw tip whether a transverse or oblique downward screw was used. Transverse screws inserted through the humeral neck from lateral to medial have the potential for damaging a small branch of the axillary nerve laterally, and care must be taken of the lateral humerus while inserting these screws. Screws inserted in a downward direction near the greater tuberosity, if originating above the equator of the humeral head, may cause impingement. PMID- 1608863 TI - Giant cell tumor of bone treated by curettage, cementation, and bone grafting. AB - Giant cell tumor, a relatively rare, occasionally malignant tumor of bone, remains a difficult therapeutic problem for the orthopedic surgeon. Various treatment options, including curettage alone, curettage with bone grafting, radiation, and curettage with acrylic cementation have been utilized and reported. Therapeutic complications such as infection, recurrence, and loss of support of the articular surface have continued to plague the treatment of giant cell tumors. This article reports the results of 10 consecutive cases of giant cell tumor of bone treated by curettage and methyl methacrylate cementation, followed by bone grafting of the surface of the lesion with demineralized bone matrix to reconstitute the cortex at the site of the tumor. At an average follow up of 36 months, eight patients had an excellent functional result and two had a fair result as scored on the Musculoskeletal Tumor Society rating system. To date, there have been no tumor recurrences or metastases, and all patients have radiographic evidence of healing of the weight bearing cortical surface. PMID- 1608864 TI - Treatment of ununited tibial fractures: a comparison of surgery and pulsed electromagnetic fields (PEMF). AB - The use of pulsed electromagnetic fields (PEMF) is gaining acceptance for the treatment of ununited fractures. The results of 44 articles published in the English language literature have been compiled to assess the effectiveness of PEMF vs surgical therapy. For ununited tibial fractures, 81% of reported cases healed with PEMF vs 82% with surgery. After multiple failed surgeries, the success rate of PEMF is reported to be greater than with surgery; this discrepancy increases with additional numbers of prior surgeries. In infected nonunions, the results of surgical treatment decreased by 21% and were less than the results utilizing PEMF (69% vs 81%). In open fractures, surgical healing exceeded PEMF (89% vs 78%), whereas in closed injuries PEMF cases healed more frequently (85% vs 79%). In general, PEMF treatment of ununited fractures has proved to be more successful than noninvasive traditional management and at least as effective as surgical therapies. Given the costs and potential dangers of surgery, PEMF should be considered an effective alternative. Experience supports its role as a successful method of treatment for ununited fractures of the tibia. PMID- 1608865 TI - Mechanical properties of 3M staples in bone block models. AB - The use of power driven staples is an accepted method of fixation for small bones of the hand and wrist and of the foot and ankle. The staples must be applied to flat or nearly flat surfaces. A synthetic model was developed to evaluate the ability of the 3M power driven staple system to resist failure due to pulling out of the staples in cantilever bending, tension, and torsion. Three different staple configurations and two leg lengths were evaluated in each of the test modes. Results indicated statistically significant differences between one and two staple configurations and between longer and shorter leg lengths. There was clear superiority of the two staple configurations and of longer leg lengths. PMID- 1608866 TI - Capitellum osteochondral injury in a football lineman. PMID- 1608867 TI - Bilateral congenital fusion of the scaphoid and trapezium in identical twins. PMID- 1608868 TI - Bilateral isolated olecranon fractures in an infant as presentation of osteogenesis imperfecta. PMID- 1608869 TI - Pathologic fracture of the femoral neck in a patient with McCune-Albright syndrome. PMID- 1608870 TI - Femur fractures associated with total hip arthroplasty. PMID- 1608871 TI - Advanced muscle training after ACL reconstruction: weeks 6 to 52. PMID- 1608872 TI - Radiologic case study. MRI in the diagnosis of synovial disease. AB - Fourteen patients with various synovial diseases were imaged using conventional radiographic techniques and MRI. We had five patients with synovial tumors, including two each with PVNS and synovial osteochondromatosis. We had five patients with infections and four patients with various other forms of arthritis. Although MRI was found to be a useful means to visualize the synovium, the findings were nonspecific except in the case of PVNS. PMID- 1608873 TI - Genetic architecture of carcass composition in chickens. AB - A cross-sectional diallel experiment was used to estimate the contribution of various types of genetic variation for the chemical components of the chicken carcass. Populations tested included a commercially developed sire line (CM), a fertility-selected broiler line (FS), and the pureline Jersey Giant (JG). Average line effects were significant for body weight and total carcass water, fat, and protein. Line effects were significant only for percentage fat and water. Maternal effects and additive sex linkage were not significant for any carcass component on an absolute or percentage basis. Significant average heterosis and sex by heterosis interactions were observed for abdominal fat pad weight and total carcass fat. Male hybrids exhibited a 29% decrease in abdominal fat pad size, but female hybrids exhibited a 7% increase. Significant heterosis was observed among females, but not males, for percentage carcass fat. Changes in carcass fat via hybridization produced the largest percentage change among males due to heterosis of the sex chromosomes. In the present experiment, negative heterosis for abdominal fat among male progeny accounted for approximately 65% of the overall reduction in fat content of the carcass. PMID- 1608874 TI - Genetic variation in total plasma and high density lipoprotein cholesterol and body weight in medium white turkeys. AB - Plasma total cholesterol (PC) and its high density lipoprotein cholesterol (HDLC) fraction were determined in 700 16-wk-old Medium White turkeys in Generation 15 of selection for low and high semen ejaculate volumes (SEV). The birds examined were from pedigree matings involving 10 sires mated to 100 dams in each line. Mean PC and HDLC were not different between lines and between sexes within lines. Genetic parameters were estimated for PC, HDLC, and BW. Sire component heritabilities estimated based on pooled data from low and high SEV lines for PC and HDLC were -.03 and .26, respectively. Genetic correlations were .05 between PC and HDLC; .13 between PC and BW; and -.34 between HDLC and BW. It was concluded that variation in PC in 16-wk-old Medium White turkeys is largely due to environmental variation and that the genetic component is largely nonadditive. However, a moderate additive genetic component was observed for HDLC. Further, determination of total PC and HDLC at 16 wk of age does not exhibit a potential value as an indicator of future SEV potential. PMID- 1608875 TI - Differential environmental effects on lesions, early growth, and mortality of imperfect albino (Sal-c) chicks. AB - A series of experiments investigated early pleiotropic effects of a gene for imperfect albinism (s(al-c) in a population of chickens at Jouy-en-Josas, France. An elevated incidence of lesions of the navel, hocks, and nares typical of imperfect albinos were seen on these chicks, confirming their existence in this population. Variations in hatching environment and the amount of light in the hatcher both implicated in contributing to the occurrence of lesions of the hocks and nares, but not to those of the naval. In two experiments, using batteries and cages, early growth was reduced among albinos and early mortality was increased. Significant genotype by environment interactions for weight at 4 days and growth to this time, but not thereafter, suggested that the effect is restricted to this time. Unfavorable environments were most deleterious to albinos. In a third experiment, conducted in floor pens, the gene had no effect on either early growth or mortality. There was no effect of the gene on the lesions, early growth, or mortality when carried by heterozygous males (s+/s(al-c)). PMID- 1608876 TI - Zinc methionine for stressed laying hens. AB - The effects of zinc methionine product (ZP) supplementation to Single Comb White Leghorn hens on egg production and quality were measured through three consecutive egg laying cycles. During the first and second lay cycles, ZP had minor or nonsignificant effects upon hen performance. During the third lay cycle, a low dietary Ca (.3% Ca) stress of 1 mo duration was encountered. During this low-Ca stress period, hens fed 1 g ZP/kg produced the greatest number of eggs (P less than .05), and during recovery from that low-Ca stress, the hens receiving 2 g ZP/kg produced the most eggs (P less than .05). The ZP appeared to help hens maintain egg size throughout this stress period. The present results indicate that ZP was beneficial to hens during low-Ca stress and during the recovery period following that stress. PMID- 1608877 TI - Abnormal feathering of chicks caused by scirpenol mycotoxins differing in degree of acetylation. AB - Graded levels of the Fusarium mycotoxins, scirpentriol (STO), 15 monoacetoxyscirpenol (15-MAS), 4,15-diacetoxyscirpenol (4,15-DAS), and 3,4,15 triacetoxyscirpenol (TAS), were fed to chicks until 3 wk of age. The primary wing feathers, which were scored visually on a scale of 1 to 5 using a newly created scoring scheme, were altered in a dose-related fashion by 15-MAS [minimum effective dose (MED) = .5 microgram/g diet], 4,15-DAS (MED = 2 micrograms/g), and STO (MED = 4 micrograms/g) but not by TAS (MED greater than 8 micrograms/g). The minimum growth inhibitory doses were 2 micrograms/g for STO, 15-MAS, and 4,15-DAS and 8 micrograms/g for TAS. The main alteration of the feathers was a frayed and missing web on the medial side of the distal half of the feather. The shafts of the feathers tended to have an accentuated medial curve. These results imply that the feather alterations associated with corn and feed infested with Fusarium spp. might be caused by trichothecene mycotoxins such as the scirpenols. PMID- 1608878 TI - Multivariate epidemiological approach to salmonellosis in broiler breeder flocks. AB - A retrospective, case-control study into risk factors of salmonellosis was undertaken using data from 111 broiler breeder flocks assembled during a 5-yr period. The results of both univariate and multivariate analyses are presented. Many different Salmonella species were detected. Multivariate models were created based on the outcome of univariate analyses. The following variables appeared to be the most relevant: disinfection tubs, hygiene barriers, the interaction of disinfection tubs by hygiene barriers, and feed mills. The final model indicated that flocks housed at farms without a disinfection tub, with poor hygiene barriers, and receiving their feed from a small feed mill had a 46.1 times greater risk of being Salmonella-positive than flocks housed at farms with a disinfection tub, with good hygiene barriers, and receiving their feed from a large feed mill. It is concluded that the application of quantitative epidemiological methods can be valuable not only to identify potential risk factors but also to quantify their contributory effect on the disease outcome. Hence, it may be a useful tool for application in "integrated food chain quality control programs". PMID- 1608879 TI - Effects of bird density on Salmonella contamination of prechill carcasses. AB - Two similar trials were conducted to evaluate the effects of bird density on Salmonella contamination of processed broilers. Commercial strain broiler chicks were reared in floor pens on new litter at densities of 557, 619, 697, 796, 929, and 1,115 cm2 per bird. Twenty percent of the chicks in each density were gavaged directly into the crop with .5 mL of 10(8) nalidixic-acid-resistant (NAR) Salmonella typhimurium on Day 2. Twenty percent of the uninoculated birds in each density category were processed at 42 days. Prechill carcasses were evaluated for NAR Salmonella incidence using the whole carcass rinse technique and a mechanical shaking device. The resulting NAR Salmonella contamination rates (from lowest to highest bird densities) were as follows, 55, 4.2, 35.7, 34.3, 88.9, and 20% in Trial 1; and 30, 20.8, 28.6, 50, 58.3, and 30% in Trial 2. A random sample of the prechill carcasses of gavaged birds indicated a contamination rate of 13.8% in Trial 1 and 61.1% in Trial 2. The NAR Salmonella contamination rates of the prechill carcasses did not appear to be affected by the bird densities evaluated in these trials. Feed intake and body weight at 42 days were adversely affected by the highest bird density, but feed utilization was not affected. PMID- 1608880 TI - Strain-cross response of heavy male broilers to dietary lysine in the finisher feed: live performance and further-processing yields. AB - A total of 2,560 male broilers from eight commercial strain-crosses were growth to 42 days of age on common starter (1 to 21 days; 23.06% CP, 3,217 kcal ME/kg) and grower (21 to 42 days; 20.14% CP, 3,224 kcal ME/kg) rations. All strain crossed subsequently received finisher diets (17.95% CP; 3,186 kcal ME/kg) containing either .85 or .95% lysine from 42 to 53 days of age. Further processing yields were determined on 12 birds per pen, selected within +/- 10% of the replicated pen (8 pens per strain-cross, 40 birds per pen) average weight. The strain-crosses differed significantly (P less than .05) in BW (1, 21, 42, and 53 days), weight gain (WG), feed:gain ratio (1 to 21 and 21 to 42 days), and mortality rate (1 to 21 days). The lysine effect during the finisher period was significant for 53-day BW and WG from 1 to 53 days. Chilled carcass (CC) and abdominal fat (AF) weights, CC yield (percentage, excluding AF), AF yield (percentage of CC weight), Pectoralis major, Pectoralis minor, total deboned breast (TDB), drumstick, thigh, wing, and residual "cage" and skin yields varied among the strain-crosses. A significant weight and yield response to lysine was observed for TDB. Variation observed among strain-cross in live performance, further-processing yields, and response to additional lysine is attributed to differences in rate of growth and degree of maturity at market age. Furthermore, the lysine requirement during the finisher period for optimum breast meat yield may be higher than that recommended by the National Research Council in 1984. PMID- 1608881 TI - Dietary effects on stunting syndrome in poults. AB - Experiments were done to determine the effect of feeding diets of different ingredient composition to poults experimentally infected with stunting syndrome (SS) at 1 day of age. In Experiment 1, feeding a complex diet (CPX) containing fish meal and sunflower meal as the main protein sources eliminated the adverse effects of SS inoculation on performance traits as compared with SS effects on poults fed a corn and soybean meal (CS) diet. In Experiments 2 and 3, the effects of SS were more severe than in Experiment 1. In these experiments, the CPX diet only partly overcame the adverse effects of SS on performance (i.e., in Experiment 2, growth depressions from 2 to 5 days of age were 90.3 and 59.6% in SS-inoculated poults fed the CS and CPX diets, respectively, as compared with uninoculated, control poults fed the same diets). Properties of the CPX diet that made it effective in reducing the severity of SS were not evident from the results of Experiment 3. Replacing soybean meal with soy protein or canola meal was ineffective as compared with the use of a mixture of sunflower meal, fish meal, meat and bone meal, and corn gluten meal. PMID- 1608882 TI - Effect of dietary energy, protein, and lysine content on performance and yields of two strains of male broiler chicks. AB - In a factorial arrangement of treatments Arbor Acres and Ross male broiler chicks were given four diets with 3,200 kcal ME/kg and four diets with 2,880 kcal ME/kg, two CP levels per energy level (23.1 and 33.6% in the high-energy diet and 21.0 and 29.7 in the low-energy diet) and two Lys levels per CP level per energy level (1.20 and 1.36% per CP level in the high-energy diets and 1.08 and 1.22% per CP level in the low-energy diets). The diets were given to 8 wk of age. Weight gain of Arbor Acres chicks was significantly higher (P less than .05) than that of Ross chicks at 6 and 7 wk of age, but feed to gain ratios were also significantly higher (P less than .05) at 6, 7, and 8 wk of age. Weight gain and feed to gain ratios were significantly better (P less than .05) on the high-energy diets than on the low-energy diets at 6, 7, and 8 wk of age. With equal Lys content, the normal-CP diets gave significantly higher gains (P less than .05) than the high CP diets at 6, 7, and 8 wk of age. With equal CP content, the high-Lys diets gave significantly more gain (P less than .05) than the normal-Lys diets at 6, 7, and 8 wk of age. Oven-ready and breast meat yields of Ross chicks were significantly higher (P less than .001) compared with those of Arbor Acres chicks at 6, 7, and 8 wk of age and yields of edible organs, skin and fat, and remaining carcass were significantly lower (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608883 TI - Influence of dietary taurine on performance and fat retention in broilers and turkey poults fed varying levels of fat. AB - Taurine, an amino acid synthesized from Met, primarily functions in bile acid conjugation. Four experiments were conducted to determine whether Tau supplementation of broiler cockerels and female turkey poults to 3 wk of age would influence performance and fat retention at different levels of dietary fat. In these experiments, Tau was added at 0 or .8% to a corn and soybean meal basal diet with dietary poultry fat added at 0, 5, or 10%. Taurine did not affect BW gain of broiler cockerels; however, in one experiment feed efficiency was improved (P less than .01) during the 1st wk and fat retention was improved (P less than .06) at 7 days of age. In experiments with turkey poults, dietary Tau did not affect weight gain but improved feed efficiency (P less than .01) during the 1st wk and decreased overall feed efficiency (P less than .01) in one experiment. Improvement of fat retention by Tau at 14 days was significant (P less than .02) in one experiment and approached significance (P less than .07) in the other experiment. Fat supplementation of both the broiler and turkey diets significantly (P less than .05) improved weight gain, feed efficiency, and fat retention. Supplementary Tau appears to have little effect on performance of broilers and turkeys. PMID- 1608884 TI - Responses of turkey poults to virginiamycin as influenced by litter condition and experimentally induced stunting syndrome. AB - Two experiments were conducted to evaluate the effect of virginiamycin (VM, 22 mg/kg of diet) on performance of uninfected (CON) turkey poults and those infected (INO) with stunting syndrome and reared on used woodshavings (Experiment 1) or on clean or used woodshavings (Experiment 2). Virginiamycin improved BW (P less than .001) and feed efficiency (FE) (P less than .05) from 1 to 29 days of age, irrespective of type of litter or disease condition. The increase in BW induced by VM, however, was greatest when poults were kept on used litter, resulting in significant (P less than .05) VM by litter interaction. Induced stunting syndrome depressed BW (P less than .01) to 29 days of age and impaired FE from 1 to 9 days of age (P less than .05) and from 5 to 9 days of age (P less than .01) in Experiments 1 and 2, respectively. Virginiamycin did not prevent early adverse effects of INO on BW and FE, but facilitated notable recovery of INO poults relative to INO poults not fed VM. Virginiamycin increased specific activities of maltase and sucrase of the jejunum of CON poults in Experiments 1 and 2; in Experiment 2, this VM effect was evident irrespective of type of litter. Maltase-specific activity and sucrase were reduced by INO (P less than or equal to .05 and P less than or equal to .01 in Experiments 1 and 2, respectively) and VM did not modify this effect. The maltase and sucrase data suggest that VM improved BW and FE of CON poults, in part, by helping to maintain digestive and absorptive functions of the small intestine during the early growth period, but, in the instance of INO poults, VM was not effective in this regard. PMID- 1608885 TI - Performance of growing pullets and laying hens fed low-protein, amino acid supplemented diets. AB - An experiment was conducted to determine the effect of feeding low-protein, amino acid-supplemented diets during growing and laying periods on performance of a commercial strain of White Leghorn chickens. The birds of the positive control were fed diets in a sequence of 20, 16, and 14% protein during 0 to 6, 6 to 12, and 12 to 18 wk (growing period) and of 18, 16.5 and 15% protein during 18 to 34, 34 to 50, and 50 to 66 wk of age (laying period). The birds of the negative control were fed protein levels of 16, 13.5, and 11.5% in the growing period and 14, 13, and 12% in the laying period. Other groups were fed the negative control series supplemented with methionine, methionine plus lysine, or methionine plus lysine plus other deficient essential amino acids. An additional group was fed the negative control supplemented with methionine plus lysine during the growing period and a protein sequence of 15, 14, and 13% supplemented with methionine and lysine during the laying period. At 18 wk of age, birds fed the negative control supplemented with methionine plus lysine or methionine plus lysine plus other deficient essential amino acids had comparable body weight to those fed the positive control despite significantly lower protein and lysine intake. Overall egg production and egg weight of birds fed the sequence of 14, 13, and 12% protein supplemented with combination of methionine, lysine, and extra levels of tryptophan and isoleucine or of the birds fed the sequence of 15, 14, and 13% protein supplemented with methionine and lysine were not different from those fed the positive control. However, egg mass and body weight were inferior to those of birds fed the positive control. PMID- 1608886 TI - Growth and tissue lipid deposition of broilers fed alpha-ketoisocaproic acid. AB - Dietary alpha-ketoisocaproic acid (KIC) was studied for effects on growth, feed efficiency, tissue cholesterol (TC) content, and immune response to a Newcastle disease virus (NDV) vaccination in broilers. In two experiments, broiler chicks were fed diets supplemented with graded levels of KIC to .54% of the diet. Feed efficiency, fat deposition, BW gain, and plasma cholesterol levels were determined at 3 wk. In a third experiment, broilers were fed diets supplemented with 0, .1, .2, and .4% KIC throughout the starter (0 to 3 wk), grower (3 to 6 wk), and finisher (6 to 7 wk) periods. Abdominal fat and plasma and breast TC were measured at 7 wk. In Experiment 4, levels of KIC to .6% were fed to broilers to determine TC content and to measure the immune response to NDV vaccination. Feed efficiency, BW gain, and percentage abdominal fat were not affected by KIC in any of the broiler experiments. The addition of KIC to broiler diets resulted in a significant reduction in breast (Pectoralis major) TC. Biceps (Biceps femoralis) TC, adductor (Pubo-ishio-femoralis) TC, and plasma cholesterol content was not affected by KIC. Geometric mean titers to NDV were not improved by KIC. The data indicate that KIC has no effect on growth or abdominal fat deposition, but may have a role in TC homeostasis. PMID- 1608887 TI - Research note: antioxidant activity of Japanese quail liver cytosol in the absence and presence of reduced glutathione. AB - The antioxidant activity of Japanese quail liver cytosol was assessed in the presence of .1, 1.0, or 10.0 mM reduced glutathione (GSH) using an in vitro assay system that utilized quail liver microsomes as the lipid substrate. The formation of malonaldehyde (MA), an indicator of lipid peroxidation, was reduced (P less than .01) by 1.0 and 10.0 mM GSH, even in the absence of cytosolic protein. Cytosolic protein at a level of 1 mg/mL of assay medium did not further reduce MA formation at any of the GSH concentrations tested. Increasing the cytosolic protein concentration to 6 mg/mL decreased (P less than .01) MA formation, even in the absence of added GSH. PMID- 1608888 TI - Stability studies of gabapentin in aqueous solutions. AB - Gabapentin is a gamma-aminobutyric acid analogue, which has been shown to be an effective antiepileptic. The solution stability of gabapentin in buffered systems was studied in order to facilitate the formulation of a liquid product. The degradation of the drug was followed as a function of pH, buffer concentration, ionic strength, and temperature. The results indicated that the rate of degradation was proportional to the buffer concentration and temperature. The pH rate profile of gabapentin degradation showed that the rate of degradation was minimum at an approximate pH of 6.0. Further, the data suggested a slower solvent catalyzed degradation rate for the zwitterionic species compared to the cationic or anionic species in the pH range of 4.5 to 7.0. There was no influence of ionic strength on the rate of degradation. Arrhenius plots of the data indicated that a shelf life of 2 years or more at room temperature may be obtained in an aqueous solution at a pH value of 6.0. PMID- 1608889 TI - Analytical method comparison based upon statistical power calculations. AB - Testing for the equivalence of results generated by different analytical methodology is a common practice in the pharmaceutical sciences. Methodology changes are implemented for both scientific and economic reasons during a scientific study. Thus, the need to demonstrate the appropriateness of considering data generated by distinct methods as part of a single information population arises. This paper describes a rapid and simple approach to the statistical design and interpretation of method comparison experiments. The approach presented is based upon a statistical power calculation technique, a knowledge of the variability associated with the methods to be compared and the criteria for equivalence (the limits within which differences become immeasurable or, for practical purposes, insignificant). Reference tables are included which show necessary sample sizes for comparison experiments for common combinations of these three variables. PMID- 1608890 TI - Initial studies on the N-glucosylation of phenobarbital by mouse liver microsomes using a radiochemical high-performance liquid chromatographic (HPLC) method. AB - A method is described for the assay of phenobarbital N-glucosylation using UDP-D [6-3H]glucose. The radioactive phenobarbital N-glucoside conjugates [(5R)-PBG, (5S)-PBG] formed during the incubations were resolved from each other and from uncharacterized radioactive products by semipreparative HPLC. The product ratio of the N-glucosides of (5R)-PBG/(5S)-PBG was 2.9 for the crude liver homogenate and 3.0 +/- 0.5 for the microsomes. Magnesium was necessary for optimal activity. The Km values for formation of (5R)-PBG, (5S)-PBG, and (5R + 5S)-PBG were 1.55 +/ 0.35, 1.27 +/- 0.14, and 1.47 +/- 0.21 mM, respectively. The Vmax values for formation of (5R)-PBG, (5S)-PBG, and (5R + 5S)-PBG were 1.34 +/- 0.05 x 10(-6), 0.43 +/- 0.01 x 10(-6), and 1.77 +/- 0.04 x 10(-6) mumol/min/mg microsomal protein, respectively. It was observed that at concentrations greater than 5 mM sodium phenobarbital, inhibition of formation of phenobarbital N-glucosides occurred. The product ratio of (5R)-PBG/(5S)-PBG is comparable to that observed in the urinary excretion studies with the mouse and opposite to that observed in urinary excretion studies in humans. PMID- 1608891 TI - Kinetics and mechanism of isomerization of cyclosporin A. AB - The kinetics of isomerization of cyclosporin A to isocyclosporin A were studied in various nonaqueous solvents as a function of temperature and added methanesulfonic acid. The rate of isomerization was found to be acid-catalyzed over the acid concentration range studied. The choice of organic solvent significantly altered the rate of isomerization. For a series of alcohols, the rate was enhanced with increasing dielectric constant of the media, however, this correlation did not hold upon introduction of the dipolar aprotic solvent, tetrahydrofuran. Conversion of cyclosporin A to isocyclosporin A in tetrahydrofuran was found to contain diminished side reactions as compared to alcoholic solvents. The rate of conversion of isocyclosporin A to cyclosporin A was determined in aqueous buffers as a function of pH, buffer concentration, and temperature. The rates of conversion were extremely rapid compared to the forward reaction. Based on the pH dependencies of dilute solution reactivities, isocyclosporin A displayed a kinetically generated pKa value of 6.9 for the secondary amine moiety. From pH 8 to pH 10 the pH-rate profile plot is linear, with a slope approximately equal to unity, indicating apparent hydroxide ion catalysis. The break in pH-rate profile suggests a change in the rate-determining step upon protonation of isocyclosporin A. The rate of isomerization in plasma was comparable with that found in a pH 7.4 buffer solution, indicating that plasma proteins do not significantly alter the isomerization kinetics of isocyclosporin A to cyclosporin A. PMID- 1608892 TI - Microbial production of a crisnatol metabolite. AB - Microbial metabolism studies of crisnatol (1), a new DNA intercalator, has resulted in the isolation and characterization of a major metabolite identified as the C-1 hydroxylated crisnatol (2). The structure of the metabolite was established by comparison of its spectral data to that of crisnatol. Complete 13C NMR assignments for crisnatol and its C-1 hydroxylated metabolite were also made. PMID- 1608893 TI - A phosphinic acid dipeptide analogue to stabilize peptide drugs during their intranasal absorption. AB - A major challenge in intranasal delivery of peptides is to overcome the enzymatic barrier that limits their absorption. Aminopeptidase inhibitors may be useful for improving systemic delivery of peptide drugs administered nasally. A phosphinic acid dipeptide analogue, a transition-state analogue aminopeptidase inhibitor in which the phosphinate moiety exists in a tetrahedral state mimicking peptides during their enzymatic hydrolysis, was synthesized and tested nasally in situ in rats. This inhibitor was found to inhibit greatly the degradation of the model peptide leucine-enkephalin in the nasal perfusate at less than or equal to 2 microM concentrations. The nasal peptidase hydrolytic activity was reversible after exposure to the inhibitor. This inhibitor has the advantage of efficacy at very low concentrations and reversibility of effects. PMID- 1608894 TI - Adsorption of fluorescein dyes on albumin microspheres. AB - The surface characteristics of bovine and egg albumin microspheres were examined using four anionic dyes; sodium fluorescein, eosin, erythrosin, rose bengal, and the cationic dye rhodamine B. The adsorption isotherms of the dyes on unloaded albumin microspheres exhibited Langmuir behavior for dilute solutions of rose bengal, erythrosin, and eosin, suggesting monolayer formation in the initial stages of the sorption process. The adsorption capacity of the microspheres for the dyes (k2) and the affinity constants of the dyes for the microspheres (k1) were found to depend on both the polarizability and the hydrophobic properties of the dye, presumably reflecting the heterogeneous character of the microsphere surface. Further, the extent of sorption at higher dye concentrations was found to depend on the ability of the dye to form stable aggregates inside the microspheres and on environmental long-range forces acting at these sites. At both low and high dye concentrations, the amount adsorbed to the microsphere surface increased with increasing hydrophobicity of the dyes. The lowest adsorption was observed for the nonsubstituted dye fluorescein, whereas the most hydrophobic dye used, rose bengal, was completely adsorbed onto the microsphere surface. The data suggest that the bovine albumin microsphere surfaces are highly hydrophobic and less porous than egg albumin microsphere surfaces. PMID- 1608895 TI - Prediction and assessment of flammability hazards associated with metered-dose inhalers containing flammable propellants. AB - Several potential replacements for chlorofluorocarbons (CFCs) in metered-dose inhalers (MDIs) are flammable. The flammability hazard associated with their use was assessed using a range of MDIs containing 0-100% (w/w) n-butane (flammable) in HFC-134a (non-flammable) fitted with either 25-, 63-, or 100-microliters metering valves or continuous valves. In flame projection tests each MDI was fired horizontally into a flame, and the ignited flume length emitted from the MDI was measured. Flame projections of greater than or equal to 60 cm were produced by all formulations fitted with continuous valves which contained greater than or equal to 40% (w/w) n-butane in HFC-134a. Using metering valves the maximum flame projection obtained was 30 cm. This was observed with a formulation containing 90% (w/w) n-butane in HFC-134a and a 100-microliters valve. For a particular formulation, smaller metering valves produced shorter flame projections. Because many MDIs are used in conjunction with extension devices, the likelihood of accidental propellant vapor ignition was determined in Nebuhaler and Inspirease reservoirs and a Breathancer spacer. Ignition was predictable based on propellant composition, metered volume, number of actuations, and spacer capacity. Calculated n-butane concentrations in excess of the lower flammability limit [LFL; 1.9% (v/v)] but below the upper flammability limit [UFL; 8.5% (v/v)] were usually predictive of flammability following ignition by a glowing nichrome wire mounted inside the extension device. No ignition was predicted or observed following one or two 25-microliters actuations of 100% n-butane into large volume Nebuhaler (750 ml) or Inspirease (660 ml) devices.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608896 TI - Analytical control procedures of immunoreactivity for IgG and Fab fragments specific to haptens. AB - This study investigates immunoreactivity control procedures, i.e., specificity, affinity constant (Ka), and specific active binding sites (SABS), for polyclonal anticolchicine, monoclonal antidigitoxin IgG and Fab fragments, and antidigoxin Fab fragments (Digidot). Preliminary control procedures for IgG and Fab fragment purity indicated that all reagents were immunologically pure. All IgG and Fab fragments exhibited similar cross-reactivity and Ka. No decrease in percentage of Fab fragment SABS was observed after papain cleavage of anticolchicine and antidigitoxin IgG. Nevertheless, only 4.3 +/- 1.2% of nonimmunopurified anticolchicine polyclonal Fab fragments and 76.2 +/- 2.3 to 88.7 +/- 2.5% of different batches of immunopurified anti-digoxin Fab (Digidot) were active, the latter percentage being in the range of the 85% specified by the manufacturer. Only 58 +/- 3% of digitoxin-specific monoclonal IgG was active and 67 +/- 7% of its Fab fragments. Results show the importance of determining the ratio of SABS to presumed total specific binding sites for pharmaceutical monoclonal and polyclonal antibody preparations against haptens. PMID- 1608897 TI - Differences in the enhancing effects of sodium caprate on colonic and jejunal drug absorption. AB - We examined the enhancing effect of sodium caprate (C10) on the jejunal absorption of a poorly absorbed drug, cefmetazole, in rats, in comparison with its colonic absorption (Pharm. Res. 5, 341-346, 1988). Jejunal absorption was significantly enhanced by C10, but to a smaller extent than colonic absorption. Membrane perturbation, caused by the interaction between C10 and membrane proteins or lipids, was shown to increase transcellular drug permeability, as reported in the colon. Paracellular permeabilities, obtained from the permeabilities of water-soluble nonelectrolytes of various molecular weights, showed a two-phase pattern against their free diffusion coefficients, suggesting the existence of at least two pore routes similar to those in the colon. C10 increased paracellular permeability in the colon but not in the jejunum. Impedance analysis and voltage clamp technique in the jejunum showed no significant effect of C10 on paracellular permeability, such as found in the colon. Accordingly, the difference in the effects of C10 on the jejunal and colonic absorption of cefmetazole was due mainly to the difference in its effects on the paracellular pathway. PMID- 1608898 TI - Gastrointestinal transit and systemic absorption of captopril from a pulsed release formulation. AB - Captopril has been administered to eight healthy male subjects by means of a pulsatile delivery system that was designed to release the drug in the colonic region of the intestine. The gastrointestinal transit and pulsatile release were followed using gamma scintigraphy. A pulsatile capsule system with release after a nominal 5-hr period was found to perform reproducibly in vitro and in vivo. In six of the eight subjects, the drug was delivered to the colon, and in the remaining two subjects, to the terminal ileum. Measurable blood levels of free captopril were found in three subjects. Variable instability of the drug in the distal intestine is suggested as a possible reason for the lack of absorption of the drug in the majority of subjects. PMID- 1608899 TI - Heat-induced drug release rate and maximal targeting index of thermosensitive liposome in tumor-bearing mice. AB - To evaluate the rate of drug release at the tumor and maximal drug targeting after administration of thermosensitive liposomes with hyperthermia, a theoretical and experimental method was derived assessing the fraction of drug released from liposomes in a single pass through the heated tumor, F, and the drug targeting index when drug release occurs completely in response to heat (F = 1), DTImax. The F and DTImax were evaluated for four types of liposomes (LUV-1 and LUV-2, thermosensitive large unilamellar liposomes; LUV-3, a nonthermosensitive large unilamellar liposome; and SUV-1, a thermosensitive small unilamellar liposome) using reported data on blood liposome levels and tumor drug levels after the liposomes were administered to tumor bearing mice. DTImax values for LUV-1 and SUV-1 were approximately 6, while the value for LUV-2 with a relatively large systemic clearance was only 2.3. The F values for LUV-1, LUV-2, and SUV-1 with hyperthermia were 0.71, 1.17, and 0.34, respectively, whereas the values for these liposomes without hyperthermia and for LUV-3 with or without hyperthermia were nearly zero. These results confirm earlier findings that LUV-1 and LUV-2 release CDDP almost completely at the heated tumor and that the large DTI value obtained in LUV-1 (DTI = 4.6) was due to its high heat sensitivity and its small systemic clearance. PMID- 1608900 TI - Predicting skin permeability. AB - Published permeability coefficient (Kp) data for the transport of a large group of compounds through mammalian epidermis were analyzed by a simple model based upon permeant size [molecular volume (MV) or molecular weight (MW)] and octanol/water partition coefficient (Koct). The analysis presented is a facile means to predict the percutaneous flux of pharmacological and toxic compounds solely on the basis of their physiocochemical properties. Furthermore, the derived parameters of the model have assignable biophysical significance, and they provide insight into the mechanism of molecular transport through the stratum corneum (SC). For the very diverse group of chemicals considered, the results demonstrate that SC intercellular lipid properties alone are sufficient to account for the dependence of Kp upon MV (or MW) and Koct. It is found that the existence of an "aqueous-polar (pore) pathway" across the SC is not necessary to explain the Kp values of small, polar nonelectrolytes. Rather, their small size, and consequently high diffusivity, accounts for their apparently larger than-expected Kp. Finally, despite the size and breadth of the data set (more than 90 compounds with MW ranging from 18 to greater than 750, and log Koct ranging from -3 to +6), the postulated upper limiting value of Kp for permeants of very high lipophilicity cannot be determined. However, the analysis is able to define the physicochemical characteristics of molecules which should exhibit these maximal Kp values.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608901 TI - Equilibrium and kinetic factors influencing bile sequestrant efficacy. AB - In vitro bile salt binding equilibria and kinetic studies were performed with cholestyramine to determine how these factors influence bile sequestrant efficacy in vivo. Chloride ion at physiologic concentrations caused more than a twofold reduction in glycocholate (GCH) binding, compared to binding in the absence of salt, over a range of GCH concentrations and was also observed to displace bound GCH. In addition, chloride ion displaced from cholestyramine as a result of bile salt binding was measured using a chloride selective electrode, and the results show that bile salt binding is due to ion exchange. Comparison of the results of the equilibrium binding experiments to human data shows that the effect of anion binding competition alone cannot account for the lack of efficacy of cholestyramine. Consideration of other effects, such as additional binding competition or poor availability for binding, based on data from the literature, shows that adequate bile salt binding potential exists and that these interferences are not major factors influencing resin efficacy. In kinetic studies, both binding uptake of GCH and displacement of GCH from cholestyramine by chloride ion were relatively rapid, indicating that cholestyramine should equilibrate rapidly with bile salts in the GI tract. Based on these findings, it is suggested that the low efficacy of cholestyramine is a result mainly of its relatively poor ability to prevent bile salt reabsorption in the ileum. PMID- 1608902 TI - Pharmacokinetic and metabolic disposition of p-chloro-m-xylenol (PCMX) in dogs. AB - The pharmacokinetic and metabolic profile of p-chloro-m-xylenol (PCMX) was studied in healthy mongrel dogs after intravenous and oral administration of single doses of 200 and 2000 mg of PCMX, respectively. Calculation of pharmacokinetic parameters was based on compartmental and noncompartmental methods. The mean pharmacokinetic parameters of elimination half-life and mean residence time were 1.84 and 1.69 hr, respectively. The apparent volume of distribution at steady state was estimated to be 22.4 liters, and the plasma clearance was 14.6 liters/hr. The bioavailability of PCMX was 21%, indicating low absorption for this drug. PCMX's metabolite data show that a presystemic elimination process (first-pass effect) is also occurring. PCMX plasma concentrations after intravenous administration of 500-, 200-, and 100-mg doses were found to be proportional to the dose given, demonstrating that the pharmacokinetic profile of PCMX is linear over the dose range studied. Biotransformation studies showed that urinary excretion was not the major route for rapid elimination of unchanged PCMX and almost all material excreted in urine was associated with the conjugated species (glucuronides and sulfates). Statistical significant differences were not found (P greater than 0.05) between the percentages excreted in urine of PCMX and its conjugated metabolites after intravenous and oral administration. The percentages excreted in urine after iv and oral doses of unchanged PCMX were, respectively, 0.45 and 0.37; total conjugates, 46.3 and 43.3; sulfates, 38.1 and 33.2; and glucuronides, 8.2 and 10.2. PMID- 1608904 TI - Esterase activity toward the diastereomers of cefuroxime axetil in the rat and dog. PMID- 1608903 TI - Effect of an acute dose of alcohol on the pharmacokinetics of oral nifedipine in humans. AB - Pharmacokinetic and pharmacodynamic interactions of alcohol and nifedipine were assessed in 10 healthy human volunteers. Doses of 20 mg (2 x 10-mg capsules) of nifedipine were administered with either 150 ml of orange juice or 75 ml of alcohol (94%) in 75 ml of orange juice according to a crossover randomized design. Plasma nifedipine levels were monitored for 16 hr after each dosing, along with pulse rate and blood pressure. The relative bioavailability of nifedipine, measured as AUC, was increased by 54% (533 vs 346 ng.hr/ml) after the dose of alcohol (P less than 0.0002). However, there were no significant differences between treatments in Cmax, tmax, or t1/2. Although there was no difference in the systolic and diastolic blood pressure and pulse rate between the two treatment groups, the time to reach peak heart rate was significantly faster in the group treated with alcohol (1.4 vs 2.2 hr). This study shows that ethanol increases the bioavailability of nifedipine and decreases the time for onset of increased heart rate. PMID- 1608905 TI - Molecular complexation: beta-cyclodextrin and benzaldehyde inclusion complex. PMID- 1608906 TI - Pharmacokinetics of droperidol in healthy volunteers following intravenous infusion and rectal administration from an osmotic drug delivery module. PMID- 1608907 TI - Enhanced bioavailability of 6-mercaptopurine after rectal administration in rats. PMID- 1608908 TI - Pharmacology of vigabatrin. AB - Vigabatrin (gamma-vinyl GABA) is a relatively new antiepileptic drug. Vigabatrin increases the concentration of gamma-aminobutyric acid (GABA) in the brain by inhibiting the major GABA metabolizing enzyme, GABA transaminase. Controlled clinical trials have demonstrated an excellent antiepileptic effect of vigabatrin, especially in the treatment of partial epilepsies. Long-term evaluations have shown no signs of tolerance development. Vigabatrin decreases the plasma concentration of phenytoin during concomitant therapy, the only drug with which an interaction seems to occur. In general, vigabatrin is well tolerated. Psychotic reactions occur in 3-6% of patients. Other frequent side effects are sedation and weight increase. Chronic vigabatrin intoxication in animals caused development of intramyelinic oedema, appearing as microvacuoles in brain white matter. No microvacuolation has been observed in humans, even after long-term treatment. Vigabatrin seems a very valuable new antiepileptic drug. PMID- 1608909 TI - Synthesis of 14C-ochratoxin A and 14C-ochratoxin B and a comparative study of their distribution in rats using whole body autoradiography. AB - Methods for preparation of labelled ochratoxin A and B are described. The method for preparation of labelled ochratoxin B involves the synthesis of the azide of ochratoxin beta via the mixed anhydride and subsequent conjugation to labelled phenylalanine to yield 14C-ochratoxin B. The labelled ochratoxins were injected into male Wistar rats and after different survival times they were sacrificed and subjected to whole body autoradiography. The distribution pattern of ochratoxin A in the rat did not differ from that earlier registered for mouse. The previously known, high susceptibility of rats (and not mice) to ochratoxin A-induced cancer could thus not be explained by an accumulation of the toxin in specific cells or organs. The distribution patterns of ochratoxin A and B were almost congruent- the only apparent difference being a much longer retention of the labelled ochratoxin A in the blood compared to ochratoxin B, which was much faster excreted. When analyzing tissue extracts for labelled metabolites only the extracts from the rats injected with ochratoxin B were found to contain easily detectable concentrations, while no metabolites of ochratoxin A were seen. PMID- 1608910 TI - Localization of gastrointestinal deposition of mercuric chloride studied in vivo. AB - During the last 5 years, the site of gastrointestinal absorption of inorganic mercury has been attempted identified mainly by experiments using perfused intestinal segments in vitro or in situ. The present investigation will discuss the localization of the absorption site for mercuric chloride based on a completely undisturbed in vivo experimental model in mice. As the mice were allowed to eat their normal diet during the experimental period, the present results would independently add to existing knowledge on intestinal absorption sites for inorganic mercury. The mice were given 203Hg labelled mercuric chloride orally, either through stomach tube or in the drinking water, and were killed after various time intervals. Mercury was localized and quantified in various segments of the gastrointestinal tract by gamma-counting. Time course analysis of the segmental deposition of mercury demonstrated that the deposition mainly takes place in the proximal jejunum and suggested that a larger part of the jejunum than previously reported is involved in absorption of mercury. Using this in vivo model, tetraethylthiuram disulfide was demonstrated to increase the intestinal deposition and absorption without changing the site of deposition. PMID- 1608911 TI - Evidence for a hazardous interaction between ethanol and the insecticide endosulfan in rats. AB - Protein supplemented diet was protective against the deleterious action of endosulfan on body growth and liver. Hepatomegaly and a reduction of body weight produced concurrently by endosulfan and ethanol were greater in male rats, suggesting that males are more susceptible than female rats to the metabolic stress caused by their interaction. Chronic endosulfan exposure resulted in a prolongation of ethanol sleeping time in female and not in male rats. This finding suggests failure of female rats to metabolize ethanol readily on account of their greater susceptibility than male rats to the hepatotoxic action of endosulfan. PMID- 1608912 TI - Effects of antioxidants on oxygen toxicity in vivo and lipid peroxidation in vitro. AB - Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferrioxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferrioxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferrioxamine (5 and 50 microM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37 degrees. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity. PMID- 1608913 TI - Aluminium-adjuvanted vaccines transiently increase aluminium levels in murine brain tissue. AB - Aluminium is widely used as an adjuvant in human vaccines, and children can often receive up to 3.75 mg of parenteral aluminium during the first six months of life. We show that intraperitoneal injection of aluminium adsorbed vaccines into mice causes a transient rise in brain tissue aluminium levels peaking around the second and third day after injection. This rise is not seen in the saline control group of animals or with vaccine not containing aluminium. It is likely that aluminium is transported to the brain by the iron-binding protein transferrin and enters the brain via specific transferrin receptors. PMID- 1608914 TI - Protection against acetaminophen hepatotoxicity by ribose-cysteine (RibCys). AB - 2(RS)-D-ribo-(1',2',3',4'-Tetrahydroxybutyl)thiazolidine-4(R)-carb oxylic acid (Ribose-Cysteine, RibCys), a latent form of L-cysteine, releases the sulfhydryl amino acid in vivo by non-enzymatic ring opening and solvolysis. The liberated L cysteine then stimulates hepatic glutathione biosynthesis. In the present studies, the efficacy of hepatoprotection by RibCys was evaluated to explore its potential utility as an acetaminophen (APAP) antidote. Protection was evaluated in the Swiss-Webster mouse model both by survival data as well as by quantitative histological criteria of hepatic damage. A dose-response study showed increased protection with increased intraperitoneal doses of RibCys ranging from 0.5 to 8.0 mmol/kg. RibCys administration 30 min. prior to and up to four hours after the APAP dose showed varying degrees of protection; however, the best protection was seen when RibCys was given shortly after APAP administration. A single RibCys dose given by the intraperitoneal or intravenous route gave better protection than when administered orally; however, RibCys given in three doses, one hour apart, regardless of the mode of administration, offered the best protection after an LD90 dose of APAP. Overall, RibCys continues to exhibit promising protective capabilities against APAP hepatotoxicity, which may be capitalized upon in clinical overdose situations. PMID- 1608915 TI - Thyroid status and hepatic thyroxine deiodinating activity under high-dose long term nitrendipine. AB - The influence of high doses of oral nitrendipine on the hypophyseal-thyroid axis and on peripheral thyroxine metabolism was studied in baboons. Administration of 320 mg oral nitrendipine per kg body weight (b.wt.) for three months caused a hypothyroid state with decreased values for thyroxine and reverse triiodothyronine, elevated TSH, but unchanged triiodothyronine; the lower doses investigated (24 and 48 mg/kg b.wt.) were without any effect. High doses of nitrendipine concomitantly increased hepatic 5'-deiodinating activity by a rise in Vmax, which could be attributed to an increase in the deiodinating enzyme content. Normal T3 serum levels in the presence of low T4 serum concentrations under high dose nitrendipine can be ascribed, at least in part, to the enhanced peripheral 5'-deiodination. PMID- 1608916 TI - Changes in rat striatum catecholamine during hypoxia with reference to protective effects of flunarizine. AB - We investigated the changes in dopamine, homovanillic acid, 3,4 dihydroxyphenylacetic acid, and norepinephrine content in striatum of rats ventilated with 5% oxygen in nitrogen gas. We also examined the effects of flunarizine, a calcium channel blocker, on these catecholamine levels. During 10 20 min. of hypoxia, the dopamine content gradually increased and the 3,4 dihydroxyphenylacetic acid and norepinephrine levels decreased, while the concentration of homovanillic acid remained unchanged. The concentrations of these substances subsequently returned to control values after 4 hr of room air breathing. In animals pretreated with intravenous flunarizine injection, there was a slight increase in dopamine, with no appreciable change in homovanillic acid or 3,4-dihydroxyphenylacetic acid content during 10-20 min. of hypoxia. The decrease in norepinephrine which occurred during 10-20 min. of hypoxia was identical between non-treated and flunarizine-treated animals. Catecholamine levels subsequently returned to control values after 4 hr of room air breathing. These results suggest that flunarizine minimizes the alterations in striatal catecholamine contents during hypoxic ventilation. PMID- 1608917 TI - Dental amalgam and mercury. AB - The mercury concentrations in blood (HgB) and urine (HgU) samples, and in exhaled air (HgAir) were measured in 147 individuals from an urban Norwegian population, using cold vapour atomic absorption spectrometry. The study aimed to estimate the mercury exposure from the dental restorations, by correlating the data to the presence of amalgam restorations. Mean values were HgB = 24.8 nmol/l, HgU = 17.5 nmol/l and HgAir = 0.8 micrograms/m3. HgU correlated with HgAir, and both HgU and HgAir with the number of amalgam restorations, amalgam restored surfaces and amalgam restored occlusal surfaces. HgB showed poor correlation to HgU and HgAir and the presence of amalgam restorations. A differentiation of the mercury absorption due to exposure from dental amalgams and from the dietary intake, necessitates measurements of both organic and inorganic mercury in the plasma, and in the erythrocytes. The results suggest that individuals with many amalgam restorations, i.e., more than 36 restored surfaces, absorb 10-12 micrograms Hg/day. PMID- 1608918 TI - Biochemical and morphological studies in testes of rat offspring of mothers exposed to styrene during lactation. PMID- 1608919 TI - The pharmacological profile of (-)deprenyl (selegiline) and its relevance for humans: a personal view. AB - (-)Deprenyl (selegiline, jumex, eldepryl, movergan) which is closely related to phenylethylamine (PEA) is a drug with a unique pharmacological spectrum. Single dose effects: (a) It is a highly potent and selective inhibitor of B-type monoamine oxidase (MAO). (b) In contrast to other MAO inhibitors it inhibits the noradrenaline releasing effect of tyramine, is therefore free of the 'cheese effect'. Multiple dose effects unrelated to MAO inhibition: (a) It enhances superoxide dismutase and catalase activity in the striatum. (b) It facilitates the activity of the nigrostriatal dopaminergic neurones. (c) It prevents age related morphological changes in the neurocytes of the substantia nigra. Consequences of multiple dose effects: Compared to salt solution-treated rats, male rats maintained on (-)deprenyl loose their capacity to ejaculate later on; retain for longer their learning ability; and live longer. Freshly diagnosed Parkinson's patients maintained on (-)deprenyl, required levodopa later than their placebo-treated peers. Patients treated with levodopa plus (-)deprenyl live longer than those on levodopa alone. Chronic treatment with (-)deprenyl improves the performance of patients with Alzheimer's disease. PMID- 1608920 TI - Studies on the mechanism of acetonitrile toxicity. I: Whole body autoradiographic distribution and macromolecular interaction of 2-14C-acetonitrile in mice. AB - Acetonitrile, a commonly used solvent is known to cause central nervous system dysfunctions. In order to gain an insight onto the mechanism of acetonitrile toxicity, we studied the kinetics of acetonitrile distribution in mice. Male ICR mice were given a tracer dose of 2-14C-acetonitrile intravenously (60 mu mol/kg or 684 mu Ci/kg, spec. act. 11.4 mCi/mmol). At various time intervals (5 min., 0.5, 1, 4, 8, 24 and 48 hr) after treatment, mice were anaesthetized and frozen by immersion in a dry ice/hexane mixture, or they were dissected for collection of organs and tissues. Frozen mice were processed for whole body autoradiography, which allows the detection of non-volatile metabolites of acetonitrile at their sites of accumulation. Covalent binding of acetonitrile metabolites in tissues was determined using trichloroacetic acid followed by ethanol/ether extraction techniques. Whole body autoradiography revealed heavy localization of acetonitrile metabolites in the gastrointestinal tissues and bile. At 5 min., the highest levels of radioactivity occurred in the liver and kidney; levels declined over time. At 24 and 48 hr, acetonitrile derived radioactivity were detected in the gastrointestine, thymus, liver and male reproductive organs. Covalent binding studies at 24 and 48 hr after treatment indicated that 40-50% of the total radioactivity present in the liver was bound to the macromolecular fractions of the tissues. The radioactivity contents of other organs were, in large part (40 50% of total), present in the lipid fraction of the tissue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608921 TI - The influence of detergents on skin barrier properties. AB - The influence of surfactants on the changes in skin barrier properties was investigated in rats. Various ionic and non-ionic surfactants were assessed using indomethacin as a model penetrant. The surfactants appeared to either increase or decrease the skin permeability, due to the properties of both compound and surfactant. Ionic surfactant sodium dodecylsulfate was the most powerful and exceeded controls by approximately 10 times measured by means of serum levels of indomethacin. Other surfactants caused concentration increase or decrease of indomethacin in serum. PMID- 1608922 TI - Effects of dietary fat composition on activities of the microsomal ethanol oxidizing system and ethanol-inducible cytochrome P450 (CYP2E1) in the liver of rats chronically fed ethanol. AB - We studied the effects of dietary fat composition on the activities of the microsomal ethanol oxidizing system (MEOS), paranitrophenol hydroxylase (PH) activity and ethanol-inducible cytochrome P450 isozymes (CYP2E1 and CYP2B1) in the liver of rats to determine the role of this ethanol metabolizing pathway in the pathogenesis of alcoholic liver disease (ALD). Wistar male rats were pair-fed a liquid diet, containing either tallow (TF) or corn oil (CF) as the fat component, and ethanol or an isocaloric amount of dextrose, through an implanted intragastric cannula. Liver pathology of rats fed ethanol (CF-ALC) and CF diet showed severe fatty change whereas the rats fed TF-alcohol and the TF and CF controls did not. MEOS activity of the CF-ALC group was 8 times of that in the CF CTL group (P less than 0.01). In TF-ALC rats, MEOS activity was increased to 2.6 times compared to that of TF-CTL (P less than 0.01). ApoCYP2E1 in CF-ALC and TF ALC were 818 +/- 63 and 433 +/- 1- pmol/mg protein, respectively, and these values were significantly higher when compared with those of the pair-fed controls (P less than 0.005). In contrast, apoCYP2B1 was increased to an equal degree in both CF-ALC and TF-ALC. When PH-activity was measured, the level of activity on TF-ALC rats did not differ from that of CF-ALC rats. Thus, ethanol induction of apoCYP2B1 (2x) and PH (6-8x) were the same for CF and TF (2x); but not for apoCYP2E1 (21 and 8x, respectively) and MEOS activity (8 and 2.6x, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608923 TI - Effect of various antidotes on biliary excretion of arsenic in isolated perfused livers of guinea pigs after acute experimental poisoning with As2O3. AB - The effect of the dithiols British Anti-Kewisite (BAL), dimercaptopropanesulfonic acid (DMPS), dimercaptosuccinic acid (DMSA) and a new metal binding agent 2,3-bis (acetylthio)- propanesulfonamide (BAPSA) on the biliary excretion of arsenic in perfused livers of guinea pigs after acute experimental poisoning with As2O3 was investigated. Guinea pigs received As2O3, 10.0 mg/kg subcutaneously at 9 a.m. as a single injection. One hour after the injection the livers were perfused (2.5 ml x min.-1 x g-1 liver) with Krebs-Henseleit buffer and glucose for 80 min. After 40 min. of saline perfusion (control) 0.1 or 0.7 mmol/l BAL, DMSA, DMPS, or BAPSA were added to the perfusate and arsenic elimination in the bile and effluent perfusate was measured. The biliary excretion of arsenic in control livers between 40 and 80 min. was 0.7% of the total arsenic liver content before perfusion (= arsenic liver content after perfusion + portion excreted in the bile+perfusate). After antidote addition (0.1 mmol/l) the excretion was 0.2% for livers perfused with BAL, 6.8% for DMSA, 10.6% for DMPS, and 11.1% for BAPSA, respectively. After 0.7 mmol/l antidote the excretion of arsenic was 0.1% in livers perfused with BAL, 9.6% for DMSA, 12.3% for DMPS, and 13.3% for BAPSA, respectively. Except BAL, all compounds and most effectively BAPSA increased biliary excretion of arsenic. This indicates that excretion of arsenic which normally is mainly renal is shifted towards faecal excretion by the dithiols. PMID- 1608924 TI - Cationic and secretory effects of glimepiride and glibenclamide in perifused rat islets. AB - The effects of glimepiride and glibenclamide upon 86Rb outflow, 45Ca outflow and insulin release were examined in rat islets perifused at low (zero to 2.8 mM) or close-to-normal (8.3 mM) D-glucose concentrations. At the low hexose concentrations, a marked and not reversible decrease in 86Rb outflow contrasted with a rapid and reversible increase in 45Ca outflow. The latter increase was abolished in the absence of extracellular Ca2+, and was not associated with any pronounced stimulation of insulin release. Inversely, in the presence of 8.3 mM D glucose, a comparable increase in 45Ca efflux now coincided with an increase in 86Rb efflux and a marked and not reversible stimulation of insulin release. Whether in terms of the time course or glucose dependency of the cationic and secretory responses, a coupled increase in both 40Ca inflow and 45Ca outflow thus coincided with either negative or positive changes in 86Rb outflow and either minimal or marked changes in insulin output. Such dissociated behaviours suggest that the insulinotropic action of hypoglycemic sulfonylureas is not necessarily attributable solely to a primary decrease in K+ conductance. PMID- 1608925 TI - Human fibroblasts lacking trans-stilbene oxide active glutathione transferase exhibit increased cell death when exposed to polycyclic aromatic hydrocarbons. AB - Glutathione transferases (GST) are detoxifying enzymes who act with many endogenous and exogenous substances such as polycyclic aromatic hydrocarbons (PAH). The GST activity towards trans-stilbene oxide (GST-tSBO) is inherited in an autosomal dominant fashion and can be separated in high (GST-positive) and low (GST-negative) phenotypes when measured in blood. Human fibroblast cultures were established from males matched for age, smoking habits and clinical manifestations of atherosclerosis. Matched pairs of GST-negative and GST-positive fibroblasts were studied. There was a very strong correlation between the levels of GST-tSBO in peripheral blood and in cultured fibroblasts within the same individual. When fibroblasts were exposed to benzo(a)pyrene (BP) or dimethylbenzanthracene (DMBA) GST-negative cells produced relatively more collagen than GST-positive cells. GST-negative fibroblasts showed a greater cell death than GST-positive fibroblasts as well among controls as after exposure to PAH. It is concluded that lack of GST-tSBO is easily discriminated in cultured skin fibroblasts. GST-negative and GST-positive fibroblasts showed different susceptibility towards some toxic stimuli that might be of importance in atherogenesis. PMID- 1608926 TI - Inhibition of ornithine aminotransferase by 5-fluoromethylornithine: protection against acute thioacetamide intoxication by elevated tissue ornithine levels. AB - 5-Fluoromethylornithine (5FMOrn) is a selective inactivator of ornithine aminotransferase. Its administration causes a dramatic increase of ornithine concentrations in all tissues. Treatment of mice with 20 mg.kg-1 5FMOrn shortly before or after a lethal dose (600 mg.kg-1, intraperitoneally) of thioacetamide (TAA), followed by a second dose 24 hr later, prevented death of 60% of the mice. Pathologic symptoms of TAA intoxication (liver haemorrhage, elevation of amino acids in blood and tissues, diminution of liver spermidine and spermine concentrations, elevation of the activity of liver enzymes in the plasma) were significantly ameliorated by the treatment. The liver protective action of 5FMOrn is related to the elevation of ornithine concentration, as appears from the fact that other, less selective inactivators of ornithine aminotransferase, also produced some protection against acute intoxication with TAA, but not a structurally related compound with no effect on this enzyme. PMID- 1608927 TI - Studies of embryotoxicity and the incidence of external malformations after continuous intravenous infusion of alpha-chaconine in pregnant rats. AB - Embryotoxicity and effects on the incidence of external malformations of the major potato glycoalkaloid alpha-chaconine (alpha-cha) were studied in rats. Pregnant Sprague-Dawley rats (n = 17) were given a continuous intravenous infusion of alpha-cha via implanted osmotic minipumps (1.7 mg/kg/day), to maintain a stable blood concentration on days 6-13 of gestation. Control animals received physiological saline solution or were left untreated, respectively. Blood serum levels of alpha-cha were monitored at selected time intervals during the treatment using a specific HPLC method. The foetal body weights and the number of resorbed or dead foetuses per litter in the alpha-cha treated group were not significantly different from the control groups. No case of malformation was detected among 143 foetuses inspected in the treated group. The average maternal blood serum concentration of alpha-cha measured during the experiment was 340 ng/ml. This is more than 20 times the average peak serum level previously reported for human volunteers after intake of potatoes with a total glycoalkaloid content at the upper safe limit for acute adverse effects. The results support the view that potato glycoalkaloids, at levels normally found in potatoes, do not present a risk for teratogenicity in humans. PMID- 1608928 TI - Intoxications with anticholinesterases: effect of different combinations of antidotes on the dynamics of acetylcholine in mouse brain. AB - Intoxications with organophosphorus compounds are normally treated with a mixture of atropine and an enzyme regenerating oxime. The addition of diazepam to the conventional drug therapy is reported to greatly improve the antidotal effect. The implication of the cholinergic system in such intoxications prompted us to study the effect of different combinations of antidotes on the acetylcholine (ACh) synthesizing system in mouse brain in vivo. The antidotes studied in this paper are diazepam, HI-6 and 1-hyoscyamine, the active enantiomer of atropine. Diazepam decreases the synthesis rate of ACh both when administered separately and in combination with 1-hyoscyamine and HI-6. This is in contrast to 1 hyoscyamine which, in addition to blocking muscarinic receptors, also increases the release and rate of synthesis of ACh, which probably is an unfavourable effect of the antidote. This might at least partly explain the advantage of combining 1-hyoscyamine and an oxime with diazepam in intoxications with anticholinesterases. Mice administered soman (0.75 x LD50), after pretreatment with the three-drug combination of antidotes, show no cholinergic symptoms despite a 50% increase in endogenous ACh. The rate of synthesis of ACh in these mice is in the same range as in animals administered diazepam alone. Mice administered the same dose of soman with no antidotal pretreatment suffer from severe tremor and salivation, and have a strongly reduced synthesis rate of ACh. PMID- 1608929 TI - Endotoxin and interleukin-1 beta induces fever and increased plasma oxytocin in rabbits. PMID- 1608931 TI - Restriction mapping of the genome of the protozoan parasite Theileria parva. AB - We have used a modified linking clone strategy and pulsed-field gel electrophoresis to derive a map of the 29 Sfi I and 4 Not I sites in the 10 million base pair genome of the protozoan parasite Theileria parva. This was achieved in the absence of classical genetic information. The map reveals four chromosomes. Several genes, including those for parasite antigens, have been located on the map, as has the single locus carrying the major repetitive sequence in this organism. The map forms the basis for a study of sexual recombination in T. parva, which will be of importance in the application of present methods of immunization. Aspects of the mapping strategy may be useful in the study of other small eukaryotic genomes. PMID- 1608930 TI - Negative regulation of Rb expression by the p53 gene product. AB - Mutation of the p53 gene is one of the most frequent genetic changes found in human cancers. Recent experiments indicated that p53 might contain a transcription-activating domain, which functions when directed to a promoter. This study shows that wild-type p53 suppresses transcription of the retinoblastoma (Rb) gene. From deletion and mutagenesis experiments, a cis-acting element (GGAAGTGA) susceptible to regulation by p53 was mapped within the Rb promoter. This element overlaps the basal transcription unit of the Rb promoter, suggesting that p53 suppresses Rb transcription through inhibition of the basal promoter activity. The N-terminal acidic and C-terminal basic domains of p53 were both required for this suppression. These findings indicate that p53 can act as a transcriptional regulator in vivo. PMID- 1608932 TI - BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. AB - We have previously identified a 95- to 100-kDa cell surface glycoprotein, which we named BEN (for bursal epithelium and neurons), that is widely expressed during chicken embryonic development. In the central nervous system, it is restricted to subsets of neurons including the motoneurons and the inferior olivary nucleus neurons (which provide the cerebellum with the climbing fibers) where its expression occurs during the phase of axonogenesis and synaptogenesis. In the present work, we show that BEN expression extends to a variety of tissues originating from the three embryonic germ layers. We have found that BEN immunopurified from neural, epithelial, and hemopoietic tissues is differently glycosylated and may or may not carry the HNK-1 epitope. We then cloned a full length cDNA encoding this protein. Analysis of its sequence reveals that BEN is a member of the immunoglobulin superfamily. Two molecules with an identical cDNA sequence were recently reported: DM-GRASP [Burns, F. R., Von Kannen, S., Guy, L., Raper, J. A., Kamholz, J. & Chang, S. (1991) Neuron 7, 209-220] and SC1 [Tanaka, H., Matsui, T., Agata, A., Tomura, M., Kubota, I., Mcfarland, K. C., Kohr, B., Lee, A., Phillips, H. S. & Shelton, D. L. (1991) Neuron 7, 535-545]. Their pattern of expression and structural properties are consistent with those reported for BEN. Therefore BEN, DM-GRASP, and SC1 are likely to be the same molecule of the immunoglobulin superfamily. PMID- 1608933 TI - Neuronal development in the Drosophila retina: the sextra gene defines an inhibitory component in the developmental pathway of R7 photoreceptor cells. AB - Mutations in a gene called sextra (sxt) have been isolated. Loss of one copy of sxt promotes R7 photoreceptor cell development in a genetically sensitized background, while loss of both copies results in precursors of non-neuronal cone cells transforming into R7 cells. The requirement for sxt function is cell autonomous. The transformation of cone-cell precursors into R7 cells occurs independently of the sevenless signal. However, the R7 precursor becomes neuronal in an sxt/sxt mutant only in a wild-type sevenless background. The genetic analysis of sxt suggests that it plays an inhibitory role, preventing cone cells from becoming neuronal. Additionally, sxt functions in R7 precursors, but the sevenless signal is essential for specification of this fate, since loss of sextra alone is unable to impart a neural fate to this cell. PMID- 1608934 TI - Enumeration of lymphokine mRNA-containing cells in vivo in a murine graft-versus host reaction using the PCR. AB - A method of enumerating lymphokine mRNA-containing cells in vivo was developed by combining limiting dilution analysis with PCR amplification of cDNA. Single-hit kinetics revealed that the PCR-limiting dilution analysis could detect a single positive cell among greater than 40,000 negative cells. With this method, spleens and lymph nodes of mice undergoing an acute allogeneic graft-versus-host reaction were found to contain lymphokine mRNA-expressing cells at frequencies of 3% for interferon gamma, 0.05% for granulocyte/macrophage colony-stimulating factor, 0.002% for interleukin 3, and 0.03% for interleukin 4; these frequencies were 20- to 175-fold higher than in lymphoid tissues of normal mice. In contrast to their low frequencies of lymphokine mRNA-containing cells in vivo, graft-versus-host reaction populations restimulated in vitro for 24 hr with anti-CD3 antibody yielded frequencies ranging from 3% for interleukin 4 to nearly 70% for interferon gamma. Furthermore, lymphokine transcripts were also detected in single micromanipulated cells from these populations. Because frequencies of anti CD3-inducible lymphokine mRNA-containing cells in normal mice were only 0.03-1%, it was concluded that lymphoid tissues of graft-versus-host reaction mice contained high frequencies of cells that had been primed for lymphokine synthesis. Only a small fraction of these cells, however, expressed lymphokine mRNAs at a given time point in vivo. PMID- 1608935 TI - A molecular mechanism for pyrimidine and purine nucleotide control of aspartate transcarbamoylase. AB - CTP (ATP) binding to the T or R state causes reorientation of several key residues and results in a decrease (increase) in the size of the nucleotide binding site and a related decrease (increase) in the extension of the outer parts of the dimer of the regulatory chains, R1 and R6. As a result, CTP pinches the regulatory dimers together by 0.3 A in the R state; ATP pushes the regulatory dimers apart by 0.3 A in the T state. These changes influence key residues in the R1-C1 interface of the R state and the R1-C1 and R1-C4 interfaces of the T state, such that the separation of catalytic trimers (c3 ... c3) is decreased by 0.5 A by CTP in the R state and increased by 0.4 A by ATP in the T state. (Smaller effects on c3 ... c3 are observed when CTP binds to the sterically crowded T state or when ATP binds to the elongated R state). These changes reorient key residues in the active site (e.g., catalytic chain residue Arg-229, a residue involved in aspartate binding). This pattern for action of CTP and ATP in perturbing the regulatory dimer, and consequently both the structure and flexibility in critical parts of the T state or R state, is called the nucleotide perturbation mechanism. PMID- 1608936 TI - Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event. AB - A series of bicyclams have been shown to be potent and selective inhibitors of human immunodeficiency virus (HIV). The compounds are inhibitory to the replication of various HIV-1 and HIV-2 strains in various human T-cell systems, including peripheral blood lymphocytes, at 0.14-1.4 microM, without being toxic to the host cells at 2.2 mM. The bicyclam JM2763 is active against 3'-azido-3' deoxythymidine (zidovudine; AZT)-resistant HIV-1 strains and acts additively with AZT. Mechanism of action studies revealed that the bicyclams (i.e., JM2763) interact with an early event of the retrovirus replicative cycle, which could be tentatively identified as a viral uncoating event. PMID- 1608937 TI - Identification of a coactivator that increases activation of transcription by serum response factor and GAL4-VP16 in vitro. AB - We have identified an activity in HeLa cell nuclear extracts that increases activation of transcription in vitro by serum response factor (SRF). This coactivator activity, termed CoS, did not affect basal (TATA only) transcription. CoS initially fractionated with transcription factors TFIIE and -F but was further purified to separate it from both TFIIE and -F as well as any other general transcription factor activity. We found that CoS was not specific for SRF activation, since it also increased transcriptional activation by the chimeric GAL4-VP16 activator. Differences among CoS and recently identified coactivators are discussed. PMID- 1608938 TI - Meiotic recombination and segregation of human-derived artificial chromosomes in Saccharomyces cerevisiae. AB - We have developed a system that utilizes human DNA-derived yeast artificial chromosomes (YACs) as marker chromosomes to study factors that contribute to the fidelity of meiotic chromosome transmission. Since aneuploidy for the YACs does not affect spore viability, different classes of meiotic missegregation can be scored accurately in four-viable-spore tetrads including precocious sister separation, meiosis I nondisjunction, meiotic chromatid loss, and meiosis II nondisjunction. Segregation of the homologous pair of 360-kilobase marker YACs was shown to occur with high fidelity in the first meiotic division and was associated with a high frequency of recombination within the human DNA segment. By using this experimental system, a series of YAC deletion derivatives ranging in size from 50 to 225 kilobases was analyzed to directly assess the relationship between meiotic recombination and meiosis I disjunction in a genotypically wild type background. The relationship between physical distance and recombination frequency within the human DNA segment was measured to be comparable to that of endogenous yeast chromosomal DNA--ranging from less than 2.0 to 7.7 kilobases/centimorgan. Physical analysis of recombinant chromosomes detected no unequal crossing-over at dispersed repetitive elements distributed along the YACs. Recombination between YACs containing unrelated DNA segments was not observed. Furthermore, the segregational data indicated that meioses in which YAC pairs failed to recombine exhibited dramatically increased levels of meiosis I missegregation, including both precocious sister chromatid separation and nondisjunction. PMID- 1608939 TI - Interlocus V-J recombination measures genomic instability in agriculture workers at risk for lymphoid malignancies. AB - V(D)J [variable-(diversity)-joining] rearrangements occur between, as well as within, immune receptor loci, resulting in the generation of hybrid antigen receptor genes and the formation of a variety of lymphocyte-specific chromosomal aberrations. Such hybrid genes occur at a low frequency in the peripheral blood lymphocytes (PBL) of normal individuals but show a markedly increased incidence in the PBL of individuals with the autosomal recessive disease ataxia telangiectasia. In this manuscript we demonstrate that the frequency of hybrid antigen-receptor genes is 10- to 20-fold increased in the PBL of an occupational group, agriculture workers, with related environmental exposures. Both ataxia telangiectasia patients and this population of agriculture workers are at increased risk for lymphoid malignancy. This result suggests that the measurement of hybrid antigen receptor-genes in PBL may be a sensitive assay for a type of lymphocyte-specific genomic instability. As a corollary, this assay may identify populations at risk of developing common types of lymphoid malignancy. PMID- 1608940 TI - A cobalt-porphyrin enzyme converts a fatty aldehyde to a hydrocarbon and CO. AB - The final step in hydrocarbon biosynthesis involves loss of CO from a fatty aldehyde. This decarbonylation is catalyzed by microsomes from Botyrococcus braunii. Among the several detergents tested for solubilizing the decarbonylase, octyl beta-glucoside (0.1%) was found to be the most effective and released 65% of the enzyme activity in soluble form. FPLC of the solubilized enzyme preparation with Superose 6 followed by ion-exchange FPLC with Mono Q resulted in 200-fold increase in specific activity with 7% recovery. The purified enzyme released nearly 1 mol of CO for each mol of hydrocarbon. SDS/PAGE of the enzyme preparation showed two protein bands of equal intensity at 66 and 55 kDa. The absorption spectrum of the enzyme with bands at 410 nm, 425 nm, 580 nm, and 620 nm suggests the presence of a porphyrin. Electron microprobe analysis revealed that the enzyme contained Co. Purification of the decarbonylase from B. braunii grown in 57CoCl2 showed that 57Co coeluted with the decarbonylase. These results suggest that the enzyme contains Co that might be part of a Co-porphyrin, although a corrin structure cannot be ruled out. Co-protoporphyrin IX itself caused decarbonylation of octadecanal at 60 degrees C, whereas the metal ion or protoporphyrin alone, or several other metal porphyrins, did not cause decarbonylation. These results strongly suggest that biosynthesis of hydrocarbons is effected by a microsomal Co-porphyrin-containing enzyme that catalyzes decarbonylation of aldehydes and, thus, reveal a biological function for Co in plants. PMID- 1608941 TI - Selection of intraepithelial lymphocytes with CD8 alpha/alpha co-receptors by self-antigen in the murine gut. AB - We have studied T-cell receptor (TCR) and alpha/alpha CD8 expression in thymus independent intraepithelial lymphocytes (TI IELs) from the gut of mice bearing transgenic (TG) TCR alpha beta specific for the male antigen, presented by H-2Db class I major histocompatibility complex (MHC) molecules. In contrast to TCR+ alpha beta cells differentiating in the thymus (from CD4+CD8+ precursors to CD4+CD8- or CD4-CD8+ progeny), TI IELs are not deleted by self-antigens, nor are they positively selected in the absence of the specific peptide. On the contrary, recognition of the antigen in the context of self-MHC is required for selection and granular differentiation of CD8+ TI IELs. Our results also show that, in contrast to the thymus, expression of the beta TG does not block expression of endogenous TCR gamma delta genes in TI IELs. The size of this gut IEL subpopulation and its difference in mechanisms of repertoire selection demonstrate the existence of a major extrathymic pathway of T-cell differentiation, the role of which remains to be elucidated. PMID- 1608942 TI - Phorbol esters stimulate the phosphorylation of c-Jun but not v-Jun: regulation by the N-terminal delta domain. AB - c-Jun and its oncogenic counterpart v-Jun are completely conserved within the region from Ser-63 to Ser-73; these serines are sites for phorbol ester-inducible c-Jun phosphorylation. Using a U937 human leukemic cell line stably expressing v Jun, we have demonstrated that phorbol esters stimulate the in vivo phosphorylation of c-Jun but not v-Jun. We developed an in vitro protein kinase assay to characterize the c-Jun protein kinase and to examine the determinants underlying this differential phosphorylation. Fusion proteins between glutathione S-transferase and the N terminus of c-Jun, v-Jun, or several c-Jun mutants were used as substrates. A c-Jun kinase activity was affinity-purified 5000-fold by using glutathione S-transferase-c-Jun-glutathione-Sepharose beads and was found to phosphorylate the N terminus of c-Jun but not v-Jun or c-Jun containing a 27 amino acid N-terminal deletion found in v-Jun. These effects were also observed in vivo as phorbol 12-myristate 13-acetate did not induce the phosphorylation of v-Jun or the c-Jun deletion mutant in U937 cell lines stably expressing these proteins. These findings indicate that the delta domain of c-Jun (amino acids 34 60), which is deleted in v-Jun, plays a critical role in regulating N-terminal c Jun phosphorylation. PMID- 1608943 TI - Extracellular (axenic) development in vitro of the erythrocytic cycle of Plasmodium falciparum. AB - Merozoites of the erythrocytic stage of Plasmodium falciparum were suspended in erythrocyte sonicate medium with ATP and pyruvate and mixed with Matrigel to form a soft gel. The gel was overlaid with complete medium; this was replaced with fresh medium at 12, 24, and 36 hr. At these times and also at 45 hr rhodamine 123 was added to some cultures and gels were sampled. Viable extracellular forms showing rhodamine fluorescence were seen: rings at 12 hr, trophozoites and early schizonts with pigment at 36 hr, and late schizonts with developing merozoites at 45 hr. These merozoites were shown to be infective to erythrocytes added to the cultures at 45 hr. Electron micrographs of 36-hr trophozoites show the organisms to have only their single plasma membrane; no parasitophorous membrane is evident. We conclude that the complex process of entry, the intactness of the host erythrocyte, and the parasitophorous membrane are not essential to the development of a merozoite through its complete asexual cycle. PMID- 1608944 TI - Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis. AB - Macrophages are thought to play an important role in the pathologic changes associated with idiopathic pulmonary fibrosis (IPF). The mechanisms for increased monocyte/macrophage recruitment in IPF are unknown. Monocyte chemoattractant protein 1 (MCP-1) is the predominant monocyte chemoattractant secreted by a variety of different cell types in culture. We examined the expression of MCP-1 mRNA and its protein product in vivo in IPF and non-IPF lung specimens by in situ hybridization and immunocytochemistry. The cell types expressing MCP-1 in vivo were identified by immunostaining with specific antibodies. We demonstrated the expression of MCP-1 mRNA in pulmonary epithelial cells, in monocytes/macrophages, and in vascular endothelial and smooth muscle cells. Lung epithelial cells in patients with IPF strongly expressed MCP-1 mRNA and its protein product. In contrast, epithelial cells in non-IPF specimens did not express MCP-1 mRNA. Macrophages and vascular endothelial and smooth muscle cells were shown to express MCP-1 in both IPF and non-IPF lung specimens. These findings provide a basis for the understanding of the in vivo physiologic processes that mediate monocyte/macrophage recruitment and infiltration in the lung interstitium and the pathologic state contributing to an increased alveolar monocyte/macrophage population and inflammation in IPF. PMID- 1608946 TI - Encoded combinatorial chemistry. AB - The diversity of chemical synthesis and the power of genetics are linked to provide a powerful, versatile method for drug screening. A process of alternating parallel combinatorial synthesis is used to encode individual members of a large library of chemicals with unique nucleotide sequences. After the chemical entity is bound to a target, the genetic tag can be amplified by replication and utilized for enrichment of the bound molecules by serial hybridization to a subset of the library. The nature of the chemical structure bound to the receptor is decoded by sequencing the nucleotide tag. PMID- 1608945 TI - Structural organization of the gene for prostaglandin D synthase in the rat brain. AB - A 3-kilobase-pair gene for rat brain prostaglandin D synthase [(5Z,13E)-(15S)-9 alpha,11 alpha-epidoxy-15-hydroxyprosta-5,13- dienoate D-isomerase, EC 5.3.99.2], which belongs to the lipocalin family, was isolated from a rat genomic DNA library by plaque hybridization with the cDNA for the enzyme. The gene contains seven exons, and all the splice donor and acceptor sites conform to the GT/AG rule. Transcription initiates at a guanine residue 39 base pairs upstream of the translation initiation codon, as determined by primer-extension analysis of rat brain mRNA. The 5'-flanking region of the gene lacks typical transcriptional regulatory sequences, such as TATA and CAAT boxes, but contains several sets of inverted repeats, direct repeats, and sequences resembling the transcriptional factor Sp1-binding site. The gene structure of prostaglandin D synthase is remarkably analogous to those of other lipocalins, such as beta-lactoglobulin, alpha 2-urinary globulin, placental protein 14, and alpha 1-microglobulin, in terms of number and sizes of exons and phase of splicing of introns. Furthermore, in a multiple alignment of the deduced amino acid sequences, positions of exon/intron junction of the prostaglandin D synthase gene are highly conserved and located around the positions of those of the genes for other lipocalins despite a weak homology. PMID- 1608947 TI - Adenylosuccinate lyase of Bacillus subtilis regulates the activity of the glutamyl-tRNA synthetase. AB - In Bacillus subtilis, the glutamyl-tRNA synthetase [L-glutamate:tRNA(Glu) ligase (AMP-forming), EC 6.1.1.17] is copurified with a polypeptide of M(r) 46,000 that influences its affinity for its substrates and increases its thermostability. The gene encoding this regulatory factor was cloned with the aid of a 41-mer oligonucleotide probe corresponding to the amino acid sequence of an NH2-terminal segment of this factor. The nucleotide sequence of this gene and the physical map of the 1475-base-pair fragment on which it was cloned are identical to those of purB, which encodes the adenylosuccinate lyase (adenylosuccinate AMP-lyase, EC 4.3.2.2), an enzyme involved in the de novo synthesis of purines. This gene complements the purB mutation of Escherichia coli JK268, and its presence on a multicopy plasmid behind the trc promoter in the purB- strain gives an adenylosuccinate lyase level comparable to that in wild-type B. subtilis. A complex between the adenylosuccinate lyase and the glutamyl-tRNA synthetase was detected by centrifugation on a density gradient. The interaction between these enzymes may play a role in the coordination of purine metabolism and protein biosynthesis. PMID- 1608948 TI - Peptide ligands for a sugar-binding protein isolated from a random peptide library. AB - Peptide ligands for the carbohydrate-binding protein concanavalin A (Con A) have been identified by screening a large, diverse peptide library expressed on the surface of filamentous phage. A dodecapeptide containing the consensus sequence Tyr-Pro-Tyr was found to bind Con A with an affinity (dissociation constant, Kd) of 46 microM, comparable to that of a known carbohydrate ligand, methyl alpha-D mannopyranoside (Kd of 89 microM). In addition the peptide inhibited precipitation of the alpha-glucan dextran 1355 by Con A. Given the complexity of oligosaccharide synthesis, the prospect of finding peptides that competitively inhibit carbohydrate-specific receptors may simplify the development of new therapeutic agents. PMID- 1608949 TI - Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1. AB - In previous studies hepatocytes undergoing cell death by apoptosis but not normal hepatocytes in rat liver showed immunostaining for transforming growth factor beta 1 (TGF-beta 1). Staining was much stronger with antibodies recognizing the pro-region of TGF-beta 1 than the mature peptide itself. Therefore we investigated the ability of both forms of TGF-beta 1 to induce apoptosis in primary cultures of rat hepatocytes. Mature TGF-beta 1 induced rounding up of the cells and fragmentation into multiple vesicles. As revealed by the DNA-specific stain H33258, the chromatin of these cells condensed and segregated into masses at the nuclear membrane; this was obviously followed by fragmentation of the nucleus. Ultrastructurally the cytoplasm was well preserved, as demonstrated by the presence of intact cell organelles. These features strongly suggest the occurrence of apoptosis. Quantification of nuclei with condensed chromatin revealed that mature TGF-beta 1 was 30-fold more effective than the TGF-beta 1 latency-associated protein complex. Finally, we administered TGF-beta 1 in vivo using an experimental model in which regression of rat liver was initiated by a short preceding treatment with the hepatomitogen cyproterone acetate. Two doses of TGF-beta 1, each 1 nM/kg, augmented the incidence of apoptotic hepatocytes 5 fold. Equimolar doses of TGF-beta 1 latency-associated protein complex were ineffective. These studies suggest that TGF-beta 1 is involved in the initiation of apoptosis in the liver and that the mature form of TGF-beta 1 is the active principle. PMID- 1608950 TI - Preferential repair and strand-specific repair of benzo[a]pyrene diol epoxide adducts in the HPRT gene of diploid human fibroblasts. AB - If excision repair-proficient human cells are allowed time for repair before onset of S phase, the premutagenic lesions formed by (+/-)-7 beta,8 alpha dihydroxy-9 alpha,10 alpha-epoxy- 7,8,9,10-tetrahydrobenzo[a]pyrene (benzo[a]pyrene diol epoxide, BPDE) are lost from the transcribed strand of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene faster than from the nontranscribed strand. No change in strand distribution is seen with repair deficient cells. These results suggest strand-specific repair of BPDE-induced DNA damage in human cells. To test this, we measured the initial number of BPDE adducts formed in each strand of the actively transcribed HPRT gene and the rate of repair, using UvrABC excinuclease in conjunction with Southern hybridization and strand-specific probes. We also measured the rate of loss of BPDE adducts from the inactive 754 locus. The frequencies of adducts formed by exposure to BPDE (1.0 or 1.2 microM) in either strand of a 20-kilobase fragment that lies entirely within the transcription unit of the HPRT gene were similar; the frequency in the 14-kilobase 754 fragment was approximately 20% lower. The rates of repair in the two strands of the HPRT fragment differed significantly. Within 7 hr after treatment with 1.2 microM BPDE, 53% of the adducts had been removed from the transcribed strand, but only 26% from the nontranscribed strand; after 20 hr, these values were 87% and 58%, respectively. In contrast, only approximately 14% of the BPDE adducts were lost from the 754 locus in 20 hr, a value even lower than the rate of loss from the overall genome (i.e., 38%). These results demonstrate strand-specific and preferential repair of BPDE adducts in human cells. They suggest that the heterogeneous repair of BPDE adducts in the human genome cannot be accounted for merely by the greatly increased rate of the repair specific to the transcribed strand of the active genes, and they point to a role for the chromatin structure. PMID- 1608951 TI - Elimination of Borrelia burgdorferi from vector ticks feeding on OspA-immunized mice. AB - Although recombinant outer surface protein A (OspA) of Borrelia burgdorferi protects mice against injected Lyme disease spirochetes, the mode of protection has not yet been explored. Indeed, the efficacy of vaccine-induced immunity against a realistic vector-mediated challenge remains unexplored. Accordingly, we determined whether this immunogen protects mice against spirochetes delivered by nymphal Ixodes dammini ticks. Following challenge by tick bite, no spirochetes could be cultured from immunized mice, and no characteristic histopathology was found. The spirochete was not detected in ticks that fed on immunized animals and was present in virtually all ticks that fed on nonimmunized mice. We conclude that OspA-immunized mice are protected from spirochetal infection, at least in part, because the spirochete is destroyed in the infecting tick. PMID- 1608952 TI - Cytokinetic failure and asynchronous nuclear division in BHK cells overexpressing a truncated protein-tyrosine-phosphatase. AB - Previous work has shown that a T-cell protein-tyrosine-phosphatase truncated in its carboxyl-terminal domain (delta C11.PTP) has full enzymatic activity but no longer localizes in the particulate fraction of the cell. Two baby hamster kidney (BHK) cell lines overexpressing the truncated protein are markedly multinucleate, a state likely caused by a failure in cytokinesis. Nuclei within syncytial cells overexpressing delta C11.PTP display a remarkable asynchronous entry into mitosis. The effects require tyrosine phosphatase activity because expression of an inactive form of the truncated enzyme yields cells indistinguishable from the parental cell line. Redistribution of the enzyme from the particulate to the soluble fraction is apparently important to these observed effects because cells overexpressing the full-length, wild-type enzyme are morphologically similar to controls. Further, when these cells contain more than one nucleus, their syncytial nuclei undergo mitosis synchronously. PMID- 1608953 TI - Identification of an interleukin 2-like substance as a factor cytotoxic to oligodendrocytes and associated with central nervous system regeneration. AB - Axons of the central nervous system in adult mammals do not regenerate spontaneously after injury, partly because of the presence of oligodendrocytes that inhibit axonal growth. This is not the case in lower vertebrates (e.g., in fish), where regeneration of the optic nerve does occur spontaneously and has been correlated with the presence of factors cytotoxic to oligodendrocytes. The present study provides evidence that the substance originating from the fish optic nerves, which is cytotoxic to oligodendrocytes, is an interleukin 2-like substance. PMID- 1608954 TI - Interaction of Escherichia coli RuvA and RuvB proteins with synthetic Holliday junctions. AB - The RuvA, RuvB, and RuvC proteins of Escherichia coli are required for the recombinational repair of ultraviolet light- or chemical-induced DNA damage. In vitro, RuvC protein interacts with Holliday junctions in DNA and promotes their resolution by endonucleolytic cleavage. In this paper, we investigate the interaction of RuvA and RuvB proteins with model Holliday junctions. Using band shift assays, we show that RuvA binds synthetic Holliday structures to form specific protein-DNA complexes. Moreover, in the presence of ATP, the RuvA and RuvB proteins act in concert to promote dissociation of the synthetic Holliday structures. The dissociation reaction requires both RuvA and RuvB and a nucleotide cofactor (ATP or dATP) and is rapid (40% of DNA molecules dissociate within 1 min). The reaction does not occur when ATP is replaced by either ADP or the nonhydrolyzable analog of ATP, adenosine 5'-[gamma-thio]triphosphate. We suggest that the RuvA and RuvB proteins play a specific role in the branch migration of Holliday junctions during postreplication repair of DNA damage in E. coli. PMID- 1608955 TI - A putative gene family in 15q11-13 and 16p11.2: possible implications for Prader Willi and Angelman syndromes. AB - The genetic defects in Prader-Willi syndrome (PWS) and Angelman syndrome (AS) map to 15q11-13. Using microdissection, we have recently isolated several DNA probes for the critical region. Here we report that microclone MN7 detects multiple loci in 15q11-13 and 16p11.2. Eight yeast artificial chromosome (YAC) clones, two genomic phage clones, and two placenta cDNA clones were isolated to analyze these loci in detail. Two of the YAC clones map to 16p. Six YAC clones and two genomic phage clones contain a total of four or five different MN7 copies, which are spread over a large distance within 15q11-13. One cDNA clone is from chromosome 15 and one is from chromosome 16. The chromosome 15 cDNA detects transcripts of 14 and 8 kilobases in various human tissues. The presence of multiple copies of the MN7 gene family in proximal 15q may conceivably be related to the instability of this region and thus to the etiology of associated disorders. PMID- 1608956 TI - Reversible in vitro growth of Alzheimer disease beta-amyloid plaques by deposition of labeled amyloid peptide. AB - The salient pathological feature of Alzheimer disease (AD) is the presence of a high density of amyloid plaques in the brain tissue of victims. The plaques are predominantly composed of human beta-amyloid peptide (beta A4), a 40-mer whose neurotoxicity is related to its aggregation. Radioiodinated human beta A4 is rapidly deposited in vitro from a dilute (less than 10 pM) solution onto neuritic and diffuse plaques and cerebrovascular amyloid in AD brain tissue, whereas no deposition is detectable in tissue without performed plaques. This growth of plaques by deposition of radiolabeled beta A4 to plaques is reversible, with a dissociation half-time of approximately 1 h. The fraction of grey matter occupied by plaques that bind radiolabeled beta A4 in vitro is dramatically larger in AD cortex (23 +/- 11%) than in age-matched normal controls (less than 2%). In contrast to the human peptide, rat/mouse beta A4 (differing at three positions from human beta A4) does not affect the deposition of radiolabeled human beta A4. beta A4 has no detectable interaction with tachykinin receptors in rat or human brain. The use of radioiodinated beta A4 provides an in vitro system for the quantitative evaluation of agents or conditions that may inhibit or enhance the growth or dissolution of AD plaques. This reagent also provides an extremely sensitive method for visualizing various types of amyloid deposits and a means for characterizing and locating sites of amyloid peptide binding to cells and tissues. PMID- 1608957 TI - A human gene (AHNAK) encoding an unusually large protein with a 1.2-microns polyionic rod structure. AB - We report here the identification and partial characterization of a human gene (designated AHNAK) that encodes an unusually large protein (approximately 700 kDa). AHNAK is expressed by means of a 17.5-kilobase mRNA in diverse cellular lineages but is typically repressed in cell lines derived from human neuroblastomas and in several other types of tumors. Unique-sequence domains at the two ends of the protein flank a large internal domain (approximately 4300 amino acids) composed of highly conserved repeated elements, most of which are 128 amino acids in length. The repeated elements in turn display a redundant motif, marked by the recurrence of proline at every seventh residue. Within these sequences, hydrophobic and hydrophilic residues alternate in a manner that is incompatible with a helical coiled-coil structure. Instead, we propose a structure resembling a beta-strand but with a periodicity of 2.33. The structure would engender a polyionic rod approximately 1.2 microns long. Preliminary evidence indicates that the protein resides predominantly within the nucleus, but no function has yet been discerned. PMID- 1608958 TI - Differentiation of renal beta-intercalated cells to alpha-intercalated and principal cells in culture. AB - The renal collecting duct is a heterogenous epithelium consisting of intercalated cells (ICC) and principal cells (PC). The origin of this cellular heterogeneity is not clear. To test the hypothesis that the two cell types might originate from one another, pure populations of ICC (beta subtype) and PC were isolated by fluorescence-activated cell sorting and grown on permeable supports. After the monolayers reached confluence, the expression of ICC- and PC-specific functions and antigens was monitored. Cultures of sorted beta-ICC, in addition to expressing ICC-specific functions (such as an electrogenic H+ secretion) and antigens, progressively acquired PC functions (amiloride-sensitive Na+ transport and K+ secretion). On day 6, cultures of sorted beta-ICC exhibited a lumen negative transepithelial potential difference of 83 +/- 4 mV and a short circuit current of 107 +/- 15 microA/cm2 and created a lumen-to-bath K+ concentration ratio of approximately 10. The percentage of cells staining with two PC-specific antibodies was 53% and 65%. On the other hand, cultures of sorted PC failed to acquire ICC-specific functions while maintaining PC characteristics. To rule out preferential proliferation of a few contaminating PC as an explanation of these results, we have generated a continuous collecting duct cell line (M-1) originating from mice transgenic for the early region of simian virus 40. Cell lines cloned from M-1 cells exhibit both PC and ICC functions and show mutually exclusive heterogenous expression of PC and ICC antigens, demonstrating a common origin of the two cell types. These data indicate that while beta-ICC in culture can give rise to both alpha-ICC and PC, PC cannot convert to ICC, which raises the possibility that beta-ICC is the stem cell in the renal collecting duct. Differentiation of ICC to PC may explain the cellular heterogeneity in the cortical collecting duct. PMID- 1608959 TI - Sodium action potentials in the dendrites of cerebellar Purkinje cells. AB - We report here that in cerebellar Purkinje cells from which the axon has been removed, positive voltage steps applied to the voltage-clamped soma produce spikes of active current. The spikes are inward, are all-or-none, have a duration of approximately 1 ms, and are reversibly eliminated by tetrodotoxin, a Na channel poison. From cell to cell, the amplitude of the spikes ranges from 4 to 20 nA. Spike latency decreases as the depolarizing step is made larger. These spikes clearly arise at a site where the voltage is not controlled, remote from the soma. From these facts we conclude that Purkinje cell dendrites contain a sufficient density of Na channels to generate action potentials. Activation by either parallel fiber or climbing fiber synapses produces similar spikes, suggesting that normal input elicits Na action potentials in the dendrites. These findings greatly alter current views of how dendrites in these cells respond to synaptic input. PMID- 1608961 TI - The mutant axolotl Short toes exhibits impaired limb regeneration and abnormal basement membrane formation. AB - The mutant axolotl Short toes develops with abnormal kidneys, Mullerian ducts, and limbs and provides one of the few experimental systems for developmental studies in amphibia. The present paper describes another deviation from this animal's normal physiology, which is very characteristic of the wild type: amputated limbs of Short toes fail to regenerate. A blastema is formed but differentiation does not occur. Detailed histological analysis provides evidence of abnormal formation of the basement membrane and accumulation of extracellular matrix within the blastema, which could be attributed to an imbalance of extracellular matrix and basement membrane proteins. The basement membrane develops much thicker and is convoluted in the arrested blastema of mutant animals. In contrast to the limbs, the tails of Short toes regenerated normally with no apparent abnormalities. No gross genomic aberrations have been detected between normal and mutant DNA, indicating that a large deletion or insertion is not likely to be the cause of this mutation. PMID- 1608960 TI - Influence of calorie restriction on oncogene expression and DNA synthesis during liver regeneration. AB - Controlling calorie intake (CCI) extends healthful life-span by a mechanism that may involve reduced rates of cell division without detriment to inducible cellular responses. To test whether inducible cellular proliferation is preserved by CCI and whether the mRNA expression levels of oncogenes activated by cell division can be reduced by CCI, we evaluated the effect of dietary energy on the hepatocellular proliferative burst and on oncogene and growth factor mRNA expression induced by partial hepatectomy. Eighty Fischer 344 rats were separated into two dietary groups and were fed semipurified diets for 10 weeks that differed only in calories by 40%. Mean hepatic levels of [3H]thymidine incorporation were greater among CCI animals at 18, 24, 28, and 36 hr after partial hepatectomy. The expression of c-fos and c-Ki-ras mRNAs, activated during hepatic regeneration, was reduced by CCI. Peak expression of c-fos among ad libitum fed controls to levels 4-6 times greater than prehepatectomy levels was not detected among CCI animals. Protracted elevated expression of c-Ki-ras among ad libitum fed animals was foreshortened by CCI. These findings demonstrate that inducible cellular proliferative responses are preserved by CCI and that the mRNA expression levels of c-fos and c-Ki-ras activated during cell division are reduced by controlling dietary energy. Preserved inducible cellular responses and lowered oncogene expression during cell division may be attributes of the healthful protective effect of CCI. PMID- 1608962 TI - Zinc regulates the function of two superantigens. AB - Staphylococcal enterotoxins bind with high affinity to class II major histocompatibility complex proteins and subsequently stimulate large numbers of T cells via the V beta portion of the T-cell receptor. Binding of enterotoxin A and enterotoxin E to HLA-DR was completely abolished by low levels of EDTA, whereas binding of toxic shock toxin was unaffected. Addition of Zn2+ to as little as 2 microM excess over EDTA completely reconstituted binding, but Ca2+, Mg2+, Cu2+, Fe2+, and Mn2+ had no effect. The dissociation constant (Kd) of 65Zn2+ binding to a single site on purified enterotoxin A was 2 microM, and addition of purified HLA-DR1 did not alter the Kd, indicating that the binding site was exclusive to enterotoxin A. In the presence of saturating levels of zinc the Kd for enterotoxin A binding to purified HLA-DR1 was 25 nM. Thus, zinc binding is an essential first step in the formation of the major histocompatibility complex binding domain of at least two bacterial superantigens. Given the measured Kd of zinc binding to enterotoxin A, serum levels of free zinc (0.2-1.0 microM) may well regulate the toxic sequelae by these two superantigens. PMID- 1608963 TI - Escherichia coli expressing a Neisseria gonorrhoeae opacity-associated outer membrane protein invade human cervical and endometrial epithelial cell lines. AB - Members of the opacity-associated (Opa) outer membrane protein family of Neisseria gonorrhoeae have been proposed to mediate adherence to and invasion of cultured human epithelial cells. We transformed Escherichia coli with a plasmid containing a gonococcal opa gene fused in-frame to the leader sequence of the beta-lactamase gene as described by Palmer et al. [Palmer, L., Brooks, G. F. & Falkow, S. (1989) Mol. Microbiol. 3, 663-671]. These transformed E. coli [E. coli (opa)] expressed the heat-modifiable opa gene product (the Opa protein) in their outer membrane and adhered to and invaded ME-180 human endocervical epithelial cells. In a 2-h adherence assay, an average of 26.7 E. coli (opa) adhered per ME 180 cell, whereas the control E. coli carrying only the expression vector (pKT279) did not adhere at all (less than 0.15 bacterium per cell). We investigated the ability of the adherent E. coli (opa) to invade ME-180 epithelial cells by using a gentamicin selection assay. We recovered up to 1 x 10(6) gentamicin-resistant bacteria per monolayer when ME-180 cells were infected with E. coli (opa) compared to less than 10 bacteria when the epithelial cells were infected with the same number of control E. coli (pKT279). The kinetics and level of invasion by E. coli (opa) were similar to invasion by Opa+ N. gonorrhoeae. Maximum invasion occurred 4 h after infection with 4 x 10(7) bacteria. Transmission electron microscopy studies confirmed that E. coli (opa) invaded ME-180 cells. In comparative studies, the number of E. coli (opa) that invaded HEC-1-B human endometrial epithelial cells was about an order of magnitude less than the number that invaded ME-180 cells, and E. coli (opa) did not invade Chang human conjunctival epithelial cells at all. The observations that early (less than 4 h) invasion by E. coli (opa) was dramatically inhibited, in a dose-responsive manner, by the actin-disrupting reagent cytochalasin D but later invasion (8-24 h) was not suggest that invasion mediated by Opa proteins may occur by two mechanisms, only one of which is dependent upon microfilament function. Transmission electron microscopy also revealed that infected epithelial cells had a dramatically increased amount of cytoplasmic fibrillar material surrounding the nucleus. The function and genesis of this material remain unclear. These studies indicate that at least one gonococcal Opa protein is an invasin. PMID- 1608964 TI - Molecular cloning of a serotonin receptor from human brain (5HT1E): a fifth 5HT1 like subtype. AB - Degenerate primers, suitable for polymerase chain reaction studies and based on the conserved structure of G protein-coupled receptors, were used to isolate cDNA clones encoding putative G protein-coupled receptors from a human hippocampal cDNA library. One clone isolated by this approach (AC1) encoded a putative receptor with 39% amino acid sequence identity to the serotonin 5HT1A receptor and 47% identity to the 5HT1D receptor. When expressed transiently in the human embryonic kidney cell line 293, AC1 cDNA-encoded receptor displayed high affinity (Kd = 15 nM) and saturability for [3H]serotonin, suggesting that AC1 encodes a 5HT1-like receptor. However, 5-carboxamidotryptamine demonstrated low affinity (pKi = 5.15) compared with serotonin (pKi = 8.14), consistent with the observed binding of the putative 5HT1E receptor. The excellent correlation observed between the pharmacology of the expressed receptor encoded by AC1 and the human brain 5HT1E binding site confirms that AC1 encodes a 5HT1E receptor and establishes a fifth 5HT1-like receptor subtype. PMID- 1608965 TI - Discrimination of DNA response elements for thyroid hormone and estrogen is dependent on dimerization of receptor DNA binding domains. AB - We and others have previously shown that a two-amino acid substitution in the base of the first zinc finger of the glucocorticoid receptor DNA binding domain (DBD) is sufficient to alter the receptor's target DNA from a glucocorticoid response element (GRE) to an estrogen response element (ERE). Activation of a thyroid hormone response element (TRE) has been shown to require an additional five-amino acid change in the second zinc finger of the thyroid hormone receptor (TR). Using closely related TRE and ERE sequences, we report that a receptor containing the TR DBD activates the ERE poorly, and receptors containing essential amino acids of the estrogen receptor (ER) DBD activate the TRE poorly. The ER DBD (expressed in Escherichia coli) selectively bound to a 32P-labeled ERE (32P-ERE) as a dimer and a 32P-TRE as a monomer, whereas the TR DBD bound 32P-TRE as a dimer and 32P-ERE as a monomer. When hybrid receptor DBDs were examined, we found that the five amino acids in the second zinc finger of the TR necessary for TRE activation were also essential for dimer formation on a TRE. Dimer formation of ER on an ERE was localized to the second half of the second zinc finger. These results suggest that the ability of ER and TR to functionally discriminate between an ERE and a TRE is a result of dimerization of their DBDs. PMID- 1608966 TI - CD4 and CD8 regulate interleukin 2 responses of T cells. AB - To characterize the T-cell surface molecules involved in regulation of T-cell interleukin 2 (IL-2) responses, we established several monoclonal antibodies (mAbs) that inhibit IL-2 responses of freshly isolated CD8+ T cells and the IL-2 dependent cell line CTLL-2. Here we show that two inhibitory mAbs are directed against Lyt-2 (CD8 alpha). In fact, all anti-Lyt-2 mAbs tested were able to inhibit the IL-2 response of the Lyt-2- and L3T4-deficient cell line HT-2 after transfection with a Lyt-2 cDNA clone. Similarly, anti-L3T4 mAbs inhibited the IL 2 response of CD4-transfected HT-2 cells. These inhibitory effects of anti-CD4 and anti-CD8 mAbs occur on normal T lymphocytes, since they also were observed with CD4+ and CD8+ T-cell blasts, and are specific for IL-2 responses, since IL-4 responses of CD4- and CD8-transfected HT-2 cells were not affected by the anti CD4 and anti-CD8 mAbs. The inhibitory effects of anti-CD4 or anti-CD8 mAbs could not be explained by interference with IL-2 binding and depended on CD4 and CD8 crosslinking, because F(ab')2 or Fab plus crosslinking second antibody, but not Fab alone, were effective. A mutant Lyt-2 molecule lacking the cytoplasmic region that mediates p56lck binding could not mediate the inhibitory effect upon crosslinking. These results suggest that CD4 and CD8 mediate negative regulation of T-cell IL-2 responses via cytoplasmically associated p56lck. PMID- 1608967 TI - Crystallization and preliminary x-ray diffraction analysis of P450terp and the hemoprotein domain of P450BM-3, enzymes belonging to two distinct classes of the cytochrome P450 superfamily. AB - Cytochromes P450 are members of a superfamily of hemoproteins that are involved in the metabolism of various physiologic and xenobiotic organic compounds. This superfamily of proteins can be divided into two classes based on the electron donor proximal to the P450: an iron-sulfur protein for class I P450s or a flavoprotein for class II. The only known tertiary structure of any of the cytochromes P450 is that of P450cam, a class I soluble enzyme isolated from Pseudomonas putida (product of the CYP101 gene). To understand the details of the structure-function relationships within and between the two classes, structural studies on additional cytochromes P450 are crucial. We report here characterization of the crystal forms of two soluble, bacterial enzymes: cytochrome P450terp [class I enzyme from a Pseudomonas species (product of CYP108 gene)] and the hemoprotein domain of cytochrome P450BM-3 [class II enzyme from Bacillus megaterium (product of the CYP102 gene)]. The crystals of cytochrome P450terp are hexagonal and belong to the space group P6(1)22 (or its enantiomorph, P6(5)22) with unit cell dimensions a = b = 68.9 A and c = 458.7 A. The crystals of the hemoprotein domain of cytochrome P450BM-3 are monoclinic and belong to the space group P2(1) with unit cell dimensions a = 59.4 A, b = 154.0 A, c = 62.2 A, and beta = 94.7 degrees. Diffraction data for the crystals of these two proteins were obtained to a resolution better than 2.2 A. Assuming the presence of two molecules in the asymmetric unit for the hemoprotein domain of P450BM-3 and one molecule for P450terp, the calculated values of Vm are 2.6 and 3.3 A3/Da, respectively. PMID- 1608968 TI - Heterodimerization of thyroid hormone (TH) receptor with H-2RIIBP (RXR beta) enhances DNA binding and TH-dependent transcriptional activation. AB - Steroid/TH receptors mediate transcriptional induction of promoters containing hormone response elements (HREs) through an unclear mechanism that involves receptor binding to both hormone and a HRE. Here we demonstrate that both HRE binding and the transcriptional inducing activities of one member of this family, TH receptor, were markedly enhanced by heterodimerization with H-2RIIBP, a non-TH binding member of the steroid hormone receptor superfamily. H-2RIIBP, the mouse homologue of human retinoic acid-related receptor, was shown to form stable heterodimers with the TH receptor either in solution or when bound to a TH response element. The results presented indicate that it might be necessary for the TH receptor or other members of this superfamily to have specific partners for heterodimer formation to elicit maximal hormone-specific gene regulation from particular HREs. PMID- 1608969 TI - Intervening sequences in an Archaea DNA polymerase gene. AB - The DNA polymerase gene from the Archaea Thermococcus litoralis has been cloned and expressed in Escherichia coli. It is split by two intervening sequences (IVSs) that form one continuous open reading frame with the three polymerase exons. To our knowledge, neither IVS is similar to previously described introns. However, the deduced amino acid sequences of both IVSs are similar to open reading frames present in mobile group I introns. The second IVS (IVS2) encodes an endonuclease, I-Tli I, that cleaves at the exon 2-exon 3 junction after IVS2 has been deleted. IVS2 self-splices in E. coli to yield active polymerase, but processing is abolished if the IVS2 reading frame is disrupted. Silent changes in the DNA sequence at the exon 2-IVS2 junction that maintain the original protein sequence do not inhibit splicing. These data suggest that protein rather than mRNA splicing may be responsible for production of the mature polymerase. PMID- 1608970 TI - Selective cleavage of thioether linkage in proteins modified with 4 hydroxynonenal. AB - The peroxidation of polyunsaturated fatty acids leads to numerous products, including 4-hydroxynonenal (HNE). That 4-hydroxy-2-alkenal compounds react with sulfhydryl groups of proteins to form thioether adducts possessing a carbonyl function has been established [Schauenstein, E. & Esterbauer, H. (1979) Ciba Found. Symp. 67, 225-244]. Taking advantage of the fact that Raney nickel catalyzes cleavage of thioether bonds, we have developed a procedure to quantitate the amount of HNE moiety bound to protein by means of a thioether linkage. Adducts of HNE with N-acetylcysteine and glutathione were prepared, labeled with NaB[3H]H4, and then treated with Raney nickel. The 3H-labeled product was recovered in 85-90% yield from both HNE-N-acetylcysteine and HNE glutathione adducts in a solvent [10% (vol/vol) methanol/chloroform]-estractable form. Treatment of proteins with HNE led to the disappearance of protein sulfhydryl groups. However, less than 10% of the labeled adducts obtained after subsequent reduction with NaB[3H]H4 could be released in a solvent-extractable form upon treatment with Raney nickel. This and the observation that HNE reacts with proteins lacking a sulfhydryl group attests to the fact that HNE can react with amino acid residues other than cysteinyl residues. PMID- 1608971 TI - Coevolution of genes and languages revisited. AB - In an earlier paper it was shown that linguistic families of languages spoken by a set of 38 populations associate rather strongly with an evolutionary tree of the same populations derived from genetic data. While the correlation was clearly high, there was no evaluation of statistical significance; no such test was available at the time. This gap has now been filled by adapting to this aim a procedure based on the consistency index, and the level of significance is found to be much stronger than 10(-3). Possible reasons for coevolution of strictly genetic characters and the strictly cultural linguistic system are discussed briefly. Results of this global analysis are compared with those obtained in independent local analysis. PMID- 1608972 TI - Specific oligosaccharide form of the Rhizobium meliloti exopolysaccharide promotes nodule invasion in alfalfa. AB - Rhizobium meliloti strain SU47 produces both high molecular weight (HMW) and low molecular weight (LMW) forms of an acidic exopolysaccharide, succinoglycan. Genetic studies have shown that succinoglycan is required for alfalfa root nodule invasion. We found that LMW succinoglycan, when applied exogenously to alfalfa roots, restored nodule invasion to exoA, exoB, exoF, and exoH mutants. Nodule initiation signals were not involved, since LMW succinoglycan from R. meliloti nodD1D2D3 and nodA mutants and from luteolin-induced wild-type cultures elicited effects similar to LMW succinoglycan from the uninduced wild-type strain. In contrast, LMW fractions from an exoA mutant, nonsuccinylated LMW succinoglycan, and HMW succinoglycan did not promote invasion, nor did LMW exopolysaccharides from R. leguminosarum bv. trifolii and Rhizobium sp. strain NGR234. LMW succinoglycan could be separated by anion-exchange chromatography into several distinct subfractions differing in repeating subunit multiplicities (monomer, trimer, and tetramer) and charge. When tested singly, only the most charged, tetrameric form was active. These results show that a specific oligosaccharide form of succinoglycan promotes nodule invasion in alfalfa. The implications for the mode of action of succinoglycan are discussed. PMID- 1608973 TI - Protein surface topology-probing by selective chemical modification and mass spectrometric peptide mapping. AB - Aminoacetylation of lysine residues and the modification of arginine by 1,2 cyclohexanedione to N7,N8-(dihydroxy-1,2-cyclohexylidene)arginine were used for probing the surface topology of hen-eggwhite lysozyme as a model protein. The molecular identification of lysine and arginine modification sites was provided by molecular weight determinations of modified and unmodified tryptic peptide mixtures (peptide mapping) using 252Cf plasma desorption mass spectrometry. At conditions of limited chemical modification, mass-spectrometric peptide-mapping analyses of lysozyme derivatives enabled the direct assignment of relative reactivities of lysine and arginine residues at different reaction times and reagent concentrations. The relative reactivities of lysine residues showed a direct correlation with their surface accessibilities from x-ray structure data. For the reaction with 1,2-cyclohexanedione, a selective modification at Arg-5, 125, -112, and -73 was identified, and an inverse correlation of relative reactivities with the surface accessibility ratios of the N7- and the N8 guanidino functions was obtained. By examination of the x-ray structural data of lysozyme, this selective modification was attributed to intramolecular catalysis because of the presence of neighboring proton acceptor groups, such as the Asp 119 carboxylate group for Arg-125 and the Trp-123 and Arg-125 carbonyl groups for Arg-5. PMID- 1608974 TI - Molecular cloning and characterization of MPL, the human homolog of the v-mpl oncogene: identification of a member of the hematopoietic growth factor receptor superfamily. AB - We have cloned the human homolog of the v-mpl oncogene transduced in the myeloproliferative leukemia retrovirus, which presents striking homologies with members of the hematopoietin receptor superfamily. We obtained two types of clones, MPLP and MPLK, which had the same 5' extremity but differed at their 3' ends. The resulting deduced polypeptides are composed of a common extracellular domain with a putative signal sequence and a common transmembrane domain, but they differ in their cytoplasmic domain after a stretch of 9 common amino acids. The extracellular domain of MPL contains the consensus sequences described for the members of the hematopoietin receptor superfamily. In addition, as for murine interleukin 3 and human and murine granulocyte-macrophage colony-stimulating factor type beta receptors, this domain can be divided into two subunits. An additional motif specific for MPL could be displayed by hydrophobic cluster analysis in the first subdomain. When RNAs from various hematopoietic cell lines were analyzed by Northern blot, MPL was detected only in the human erythroleukemia (HEL) cell line as a major 3.7-kilobase (kb) mRNA (MPLP) and a minor 2.8-kb mRNA (MPLK). However, study of MPL expression by PCR analysis indicated that MPL is expressed at a low level in a large number of cells of hematopoietic origin and that the two types of mRNAs (P and K) were always found to be coexpressed. PMID- 1608975 TI - A metastatic nude-mouse model of human pancreatic cancer constructed orthotopically with histologically intact patient specimens. AB - Pancreatic cancer is one of the most intractable and least understood of all human cancers. Pancreatic cancers is the fourth-leading cause of cancer-related mortality in the United States with less than 2% of the patients surviving for 5 yr. In an effort to help develop more effective treatment modalities for pancreatic cancer and improve detection, we report an animal model for individual human pancreatic-cancer patients. The model involves orthotopic transplantation of histologically intact pancreatic-cancer specimens to the nude-mouse pancreas, which can result in models that resemble the clinical picture including (i) extensive local tumor growth, (ii) extension of the locally growing human pancreatic cancer to the nude-mouse stomach and duodenum, (iii) metastases of the human pancreatic tumor to the nude-mouse liver and regional lymph nodes, and (iv) distant metastases of the human pancreatic tumor to the nude-mouse adrenal gland, diaphragm, and mediastinal lymph nodes. In a series of five patient cases, a 100% take rate has been demonstrated, and of 17 mice transplanted, 15 supported tumor growth. Immunohistochemical analysis of the antigenic phenotype of the transplanted human pancreatic tumors showed a similar pattern of expression of two different human tumor-associated antigens, such as tumor-associated glycoprotein 72 and carcinoembryonic antigen in the transplanted tumors when compared with the original surgical biopsy, suggesting similarity between the two. This model should, therefore, prove valuable for treatment evaluation of individual cancer patients, as well as for evaluation of experimental treatment modalities for this disease. PMID- 1608976 TI - The patA gene product, which contains a region similar to CheY of Escherichia coli, controls heterocyst pattern formation in the cyanobacterium Anabaena 7120. AB - In Anabaena 7120, heterocysts (cells specialized for nitrogen fixation) develop at the ends of filaments and at intervals within each filament. We have isolated a mutant Anabaena strain that develops heterocysts mostly at the ends of filaments. This mutant, PAT-1, grows poorly under nitrogen-fixing conditions. The wild-type gene that complements the mutation in PAT-1, called patA, was cloned and sequenced. The predicted PatA protein contains 379 amino acids distributed among three "domains" based on predictions of hydropathy and flexibility. The carboxyl-terminal domain is very similar to that of CheY and other response regulators in two-component regulatory systems in eubacteria. The patA mutation suppresses the multiheterocyst phenotype produced by extra copies of the wild type hetR gene described previously, suggesting that PatA and HetR are components of the same environment-sensing regulatory circuit in Anabaena. PMID- 1608977 TI - Coherent 25- to 35-Hz oscillations in the sensorimotor cortex of awake behaving monkeys. AB - Synchronous 25- to 35-Hz oscillations were observed in local field potentials and unit activity in sensorimotor cortex of awake rhesus monkeys. The oscillatory episodes occurred often when the monkeys retrieved raisins from a Kluver board or from unseen locations using somatosensory feedback; they occurred less often during performance of repetitive wrist flexion and extension movements. The amplitude, duration, and frequency of oscillations were not directly related to movement parameters in behaviors studied so far. The occurrence of the oscillations was not consistently related to bursts of activity in forearm muscles, but cycle-triggered averages of electromyograms revealed synchronous modulation in flexor and extensor muscles. The phase of the oscillations changed continuously from the surface to the deeper layers of the cortex, reversing their polarity completely at depths exceeding 800 microns. The oscillations could become synchronized over a distance of 14 mm mediolaterally in precentral cortex. Coherent oscillations could also occur at pre- and postcentral sites separated by an estimated tangential intracortical distance of 20 mm. Activity of single units was commonly seen to burst in synchrony with field potential oscillations. These findings suggest that such oscillations may facilitate interactions between cells during exploratory and manipulative movements, requiring attention to sensorimotor integration. PMID- 1608978 TI - Dynamic magnetic resonance imaging of human brain activity during primary sensory stimulation. AB - Neuronal activity causes local changes in cerebral blood flow, blood volume, and blood oxygenation. Magnetic resonance imaging (MRI) techniques sensitive to changes in cerebral blood flow and blood oxygenation were developed by high-speed echo planar imaging. These techniques were used to obtain completely noninvasive tomographic maps of human brain activity, by using visual and motor stimulus paradigms. Changes in blood oxygenation were detected by using a gradient echo (GE) imaging sequence sensitive to the paramagnetic state of deoxygenated hemoglobin. Blood flow changes were evaluated by a spin-echo inversion recovery (IR), tissue relaxation parameter T1-sensitive pulse sequence. A series of images were acquired continuously with the same imaging pulse sequence (either GE or IR) during task activation. Cine display of subtraction images (activated minus baseline) directly demonstrates activity-induced changes in brain MR signal observed at a temporal resolution of seconds. During 8-Hz patterned-flash photic stimulation, a significant increase in signal intensity (paired t test; P less than 0.001) of 1.8% +/- 0.8% (GE) and 1.8% +/- 0.9% (IR) was observed in the primary visual cortex (V1) of seven normal volunteers. The mean rise-time constant of the signal change was 4.4 +/- 2.2 s for the GE images and 8.9 +/- 2.8 s for the IR images. The stimulation frequency dependence of visual activation agrees with previous positron emission tomography observations, with the largest MR signal response occurring at 8 Hz. Similar signal changes were observed within the human primary motor cortex (M1) during a hand squeezing task and in animal models of increased blood flow by hypercapnia. By using intrinsic blood-tissue contrast, functional MRI opens a spatial-temporal window onto individual brain physiology. PMID- 1608980 TI - Archaea in coastal marine environments. AB - Archaea (archaebacteria) are a phenotypically diverse group of microorganisms that share a common evolutionary history. There are four general phenotypic groups of archaea: the methanogens, the extreme halophiles, the sulfate-reducing archaea, and the extreme thermophiles. In the marine environment, archaeal habitats are generally limited to shallow or deep-sea anaerobic sediments (free living and endosymbiotic methanogens), hot springs or deep-sea hydrothermal vents (methanogens, sulfate reducers, and extreme thermophiles), and highly saline land locked seas (halophiles). This report provides evidence for the widespread occurrence of unusual archaea in oxygenated coastal surface waters of North America. Quantitative estimates indicated that up to 2% of the total ribosomal RNA extracted from coastal bacterioplankton assemblages was archaeal. Archaeal small-subunit ribosomal RNA-encoding DNAs (rDNAs) were cloned from mixed bacterioplankton populations collected at geographically distant sampling sites. Phylogenetic and nucleotide signature analyses of these cloned rDNAs revealed the presence of two lineages of archaea, each sharing the diagnostic signatures and structural features previously established for the domain Archaea. Both of these lineages were found in bacterioplankton populations collected off the east and west coasts of North America. The abundance and distribution of these archaea in oxic coastal surface waters suggests that these microorganisms represent undescribed physiological types of archaea, which reside and compete with aerobic, mesophilic eubacteria in marine coastal environments. PMID- 1608981 TI - [Tetrahydroisoquinolines--endogenous products from chronic alcohol abuse]. PMID- 1608979 TI - Eight base changes are sufficient to convert a leucine-inserting tRNA into a serine-inserting tRNA. AB - Each aminoacyl-tRNA synthetase must functionally distinguish its cognate tRNAs from all others. We have determined the minimum number of changes required to transform a leucine amber suppressor tRNA to serine identity. Eight changes are required. These are located in the acceptor stem and in the D stem. PMID- 1608982 TI - [The use of bead cellulose for controlled drug liberation. 4. Binding of bead cellulose and bead cellulose-derivatives with prazosin hydrochloride and its liberation]. AB - Pure bead cellulose and the ionic derivatives carboxymethyl and dihydrogen phosphate bead cellulose were coupled with prazosin hydrochloride. The degree of substitution achieved during loading mostly depends on the number of functional groups, what was verified by titrimetric determination of the ion exchange capacity. Because of predominant ionic binding of the protonated prazosin cation to the anionic groups of several types of bead cellulose in electrolytes containing liquids as well as in water a large amount of bonded drug is liberated considerable fast. Retardation of the liberation in comparison to the commercial product Adversuten is verified but not applicable to therapeutic use in the case of prazosin. PMID- 1608983 TI - Influence of emulsoid vehicle on the release and activity of allantoin. AB - Samples which contain 2% (w/w) of allantoin in various emulsified vehicles were prepared and characterized. The influence of vehicle on releasing and diffusion of allantoin through semipermeable membrane into an aqueous medium was examined and the quantity of released allantoin was estimated spectrophotometrically. The best results were achieved with ambiphilic vehicle emulsified with complex Tagat S-Tegin M which in the aqueous phase contained propylene glycol (sample A2). On the contrary, with both lanacolic vehicles, the poorest results were achieved in vitro. On the basis of the results for clinical evaluation, the best preparation was chosen (A2) and the preparation with lanacolic vehicle which contains propylene glycol (B2). Before the application of samples, each patient was tested for irritation and sensitization. All test were negative. During further clinical examinations on patients suffering from psoriasis an open double trial for the duration of 14 d was performed. For the evaluation of the efficacy of the examined preparations, objective parameters of the clinical picture were observed (the state of hyperkeratosis, of erythema and infiltration) as well as subjective parameters which were evaluated by the patients themselves. When the in vitro results are compared with clinical estimation, it is evident that they correspond only when characteristics of the preparation are estimated by patients (smearing, absorption and feeling on the skin), because the best preparation was in these cases A2. Both preparations are equally good when regression of subjective symptoms is evaluated (itching and burning). In the objective evaluation of the regression of visible symptoms, such as hyperkeratosis and erythema, results of the clinical experiment do not correspond with results in vitro.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1608985 TI - Lack of effect of diacetyl-splenopentin (Berlopentin) on the pharmacokinetics of caffeine. AB - The influence of Berlopentin on caffeine clearance was measured after a 6 week i.v. treatment or a 4 week s.c. administration within a phase I trial. It was demonstrated that therapy with Berlopentin did not affect significantly caffeine elimination. Thus, clearance of drugs which are biotransformed by hepatic microsomal oxidation are unlikely to be affected by the coadministration of Berlopentin. PMID- 1608984 TI - [The pharmacokinetic behavior of AWD 26-06 in humans following single and multiple administration]. AB - The pharmacokinetics of the muscarinolytic drug AWD 26-06 was investigated in two subjects after a single dose of 50 and 100 mg, respectively, and with six subjects after repeated dosage. The half time (t1/2) is 2.4 and 2.6 h, respectively, the height of the concentration maximum (Cmax) 500 and 1400 ng.ml 1, respectively, and the area under the curve (AUC) 2155 and 4334 ng.ml-1.h, respectively. The repeated dosage (25 mg every 8 h for 7 d) showed a small increase of the serum level. The t1/2 and the mean residence time (MRT) at the 1st and the 8th d are 2.6 h (range: 1.8-2.9 h) and 4 h (range: 2.7-5.8 h), respectively. The point (tmax) and the Cmax were not different at the 1st and 8th d: mean tmax (1st d) 1.1 h (range: 1.0-1.5 h), mean tmax (8th d) 0.9 h (range: 0.75-1.0 h); Cmax (1st d) 227 ng.ml-1 (range: 160-320 ng.ml-1), Cmax (8th d) 282 ng.ml-1 (range: 168-320 ng.ml-1). There were also no differences for the AUC0-t at the 1st and 8th d (1st d) 815 ng.ml-1.h (range: 610-1134 ng.ml-1.h). The simulation of the serum level by means of the data from the single dose were established by this investigation. Typical subjective muscarinolytic symptoms (e.g. dryness of the mouth, diminution of accommodation) were observed after the 2nd/3rd dosage. These signs diminished 24-36 h after discontinuation of the dosage. The parameter ALAT, proteins of plasma, and blood cell count were not changed at the end of therapy in comparison to the beginning. PMID- 1608986 TI - Nalidixic acid prodrugs: amides from amino acid esters and nalidixic acid. PMID- 1608987 TI - [Synthesis and biological activity of 1,4-disubstituted thiosemicarbazides and their 1,2,4-triazole-5-thione derivatives]. PMID- 1608988 TI - Study of local anaesthetics. Part 100(3): Partition coefficients and local anaesthetic activity of some derivatives of alkoxy substituted phenylcarbamic acids. PMID- 1608989 TI - [Pharmaceutical bioavailability of chlortetracycline in various ointment bases]. PMID- 1608990 TI - Difference in the inhibition of plasma cholinesterase activity by anti-emetic metoclopramide in humans and mice. PMID- 1608991 TI - In vivo antitumor activity of 5-hydroxy-6-[N,N-bis(2 chloroethyl)aminomethyl]naphthalene-1,8- carbolactone. PMID- 1608992 TI - Therapeutic efficacy of bis-pyridinium oximes against diisopropyl fluorophosphate (DFP) and soman intoxication in rodents. PMID- 1608993 TI - The effects of exercise on blood flow with reference to the human cardiovascular system: a finite element study. AB - This paper reports on a theoretical investigation into the effects of vasomotion on blood through the human cardiovascular system. The finite element method has been used to analyse the model. Vasoconstriction and vasodilation may be effected either through the action of the central nervous system or autoregulation. One of the conditions responsible for vasomotion is exercise. The proposed model has been solved and quantitative results of flows and pressures due to changing the conductances of specific networks of arterioles, capillaries and venules comprising the arms, legs, stomach and their combinations have been obtained. PMID- 1608994 TI - Light scattering study of irradiated lipid bilayer. AB - Vesicular phospholipid bilayer membranes in the form of giant unilamellar vesicles (GUVs) of dipalmitoylphosphatidylcholine (DPPC) were irradiated with fast neutron fluences ranging from 10(4) to 10(7) n cm-2. The phase behaviour of both non-irradiated and irradiated GUVs was investigated using an angular light scattering technique. A model independent size distribution of the samples and their optical anisotropy (delta) were determined using a maximum entropy technique and the theory of light scattering from spherical shells composed of anisotropic cylindrical molecules arranged radially in the shells. The structural changes in the lipid bilayer exposed to fission neutrons are discussed on the basis of the damaging mechanisms of fast neutrons to both the hydrophobic and hydrophilic regions of the lipid bilayer. PMID- 1608995 TI - Excitation characteristics of adiabatic half-passage RF pulses used in surface coil MR spectroscopy. Application to 13C detection of glycogen in the rat liver. AB - Properties of sech/tanh and sin/cos half-passage RF pulses are discussed in view of their use in surface coil MR spectroscopy. We focus on the use of these pulses in a regime which is partially adiabatic, i.e. not strictly adiabatic off resonance, while on-resonance the adiabaticity condition is fulfilled. It is shown that the frequencies of the singular points of the excitation profiles, as well as their number, depend on the B1 field. This leads to a signal intensity reduction from off-resonance spectral regions over much broader ranges than generally believed. We show in particular that with surface coil, sin/cos RF pulses may perform particularly well, providing optimal excitation on resonance and a desired attenuation over a broad spectral range off-resonance. This feature is applied for the in vivo detection of rat liver glycogen by means of 13C MR spectroscopy. Under suitable RF power conditions, a remarkable attenuation of the signals from the saturated carbons of the subcutaneous fat can be achieved. PMID- 1608996 TI - Comparison of two methods of quantitation in human studies of biodistribution and radiation dosimetry. AB - A simple method of quantitating organ radioactivity content for dosimetry purposes, based on relationships between organ count rate and the initial whole body count rate, has been compared with a more rigorous method of absolute quantitation using a transmission scanning technique. Comparisons were on the basis of organ uptake (% administered activity) and resultant organ radiation doses (mGy MBq-1) in 6 normal male volunteers given a 99Tcm-labelled myocardial perfusion imaging agent intravenously at rest and following exercise. In these studies, estimates of individual organ uptakes by the simple method were in error by between +24 and -16% compared with the more accurate method. However, errors on organ dose values were somewhat less and the effective dose was correct to within 3%. These radiation dose effects were largely influenced by radioactivity in the remaining body (i.e. excluding the organs specifically analysed) which accounted for the major proportion of the 99Tcm residence time. Effects due to different biodistributions between rest and exercise studies were also observed and it is concluded that although the simple method was acceptable for the present dosimetry study it should only be used with caution, and a more accurate method is recommended. PMID- 1608997 TI - Error analysis of combined measurements of regional ventilation and V/Q ratio using positron emission tomography. AB - We measured the regional pulmonary ventilation/perfusion ratio with intravenous 13N in saline solution, using positron emission tomography, in eight normal healthy volunteers, 10 patients with asthma and 10 patients with chronic obstructive pulmonary disease. Regional pulmonary ventilation was also measured with 19Ne, and this information was used to (i) correct ventilation/perfusion ratios obtained with 13N in regions with impaired ventilation and (ii) calculate regional perfusion, Q. In this paper we analyse the errors inherent in these measurements. Dead space ventilation and focal inhomogeneities in ventilation and/or blood flow will affect the transport of both 19Ne and 13N, but in different ways. Combining the two methods, values of blood flow obtained tend to overestimate Q in normal supine subjects by some 6% in the non-dependent part of the lung and to underestimate Q by a similar amount in the dependent part. In patients with air flow obstruction, blood flow is underestimated in regions with low ventilation/perfusion ratios and overestimated in regions with high ventilation/perfusion ratios. In the groups of patients studied, errors may reach a level of 10-20%. The limitations of the method in regions with extensive gas flow and/or blood flow heterogeneities are discussed on a theoretical basis and in some extreme conditions blood flow may be overestimated by a factor of two to three. PMID- 1608998 TI - Monte Carlo modelling of the performance of a rotating slit-collimator for improved planar gamma-camera imaging. AB - Planar imaging with a gamma camera is currently limited by the performance of the collimator. Spatial resolution and sensitivity trade off against each other; it is not possible with conventional parallel-hole collimation to have high geometric sensitivity and at the same time excellent spatial resolution unless field-of-view is sacrificed by using fan- or cone-beam collimators. We propose a rotating slit-collimator which collects one-dimensional projections from which the planar image may be reconstructed by the theory of computed tomography. The performance of such a collimator is modelled by Monte Carlo methods and images are reconstructed by a convolution and backprojection technique. The performance is compared with that of a conventional parallel-hole collimator and it is shown that higher spatial resolution with increased sensitivity is possible with the slit-collimator. For a point source a spatial resolution of some 6 mm at a distance of 100 mm from the collimator with a x7 sensitivity compared with a parallel-hole collimator was achieved. Applications to bone scintigraphy are modelled and an improved performance in hot-spot imaging is demonstrated. The expected performance in cold-spot imaging is analytically investigated. The slit collimator is not expected to improve cold-spot imaging. Practical design considerations are discussed. PMID- 1608999 TI - A numerical method for electron transport calculations. AB - A numerical algorithm for calculating the penetration of electrons in dense media is presented. The numerical algorithm is intended for future application to radiotherapy dose calculations. The method is generic in the sense that it may be used with different theoretical models describing the angular scattering of electrons with depth. It is also general enough that it may be applied to electron dose calculations in heterogeneous as well as homogeneous media. The assumptions used in the algorithm are examined and equations describing the evolution of the distribution of electrons with depth are presented. Calculations have been performed for 10 MeV broad beams and pencil beams incident on water. It is shown that the Fermi-Eyges analytical solutions are recovered if the angular scattering process is assumed to be a Gaussian Markov process and the cumulative angle of electron travel remains small. In the case where the small angle approximation is not imposed, the numerical method qualitatively reproduces, at large depths, the wide angle scattering 'tails' seen in Monte Carlo generated profiles. PMID- 1609000 TI - W values and other transport data on low energy electrons in tissue equivalent gas. AB - The degradation of low energy electrons in a methane based, tissue equivalent gas was studied experimentally by ionization chamber experiments and theoretically by Monte Carlo electron transport simulation in the energy range between 25 eV and 5 keV. From measured ionization yields and calculated ionization and energy dissipation profiles, the mean energy W required to produce an ion pair, the differential omega value, backscatter coefficients, different types of mass ranges, and stopping powers were determined. A comparison of our experimental results with those of the calculations shows a very satisfactory agreement in the whole energy range. In addition to these data some quantities of interest in the fields of radiation biology and microdosimetry, such as the statistical fluctuation of ionization yields, the energy transfer to and the ionization yields in thin material layers of the tissue equivalent gas, together with the distance distribution of energy transfer and the dose average of the specific energy, have been studied. A comparison of these results with those for electrons in water showed the great similarity of both stopping media for many purposes in the fields of radiation research. PMID- 1609001 TI - On the calibration of plane-parallel ionization chambers for electron beam dosimetry. AB - The procedure recommended by different dosimetry protocols for the determination of the absorbed dose to air chamber factor, ND,pp, of plane-parallel chambers, comparing absorbed dose determinations in a high-energy electron beam with a reference cylindrical chamber having a known ND,cyl factor, has been investigated. Attention has been focused on the case that the chamber serving as reference has a solid aluminium central electrode. It has been found that using a wide spread Farmer-type chamber (NE 2571), together with recommendations which specifically take into account central electrode corrections for electron beam dosimetry, kcelpcel = pcel-global(IAEA) = 1.008, yields inconsistent results compared with those obtained from a fully homogeneous ionization chamber; for the NE 2571 chamber, a value kcelpcel = pcel-global(IAEA) congruent to 1.0 has been obtained. Analytical calculations of kmkatt for Farmer-type cylindrical chambers and experimental determinations of the product kmkattkcelpcel in electron beams agree within experimental uncertainties, with no evidence of statistical significance for the commonly used assumption pcel = 1, which yields a 0.8% correction (due to kcel only) for the effect of the NE 2571 aluminium electrode in electron beam dosimetry. The use of a 'NACP-chamber' specific factor (kpp or kmkatt) to obtain ND,pp from NK,pp in NACP plane-parallel chambers has been found unsatisfactory, and direct experimental determinations of ND,pp are recommended instead. It is suggested that Standard Dosimetry Laboratories provide ND,pp calibration factors in 60Co beams. PMID- 1609002 TI - First x-ray images with a double-sided microstrips silicon crystal. A novel detector for digital radiography? PMID- 1609003 TI - Brief exposures to weak static magnetic field during early embryogenesis cause cuticular pattern abnormalities in Drosophila larvae. PMID- 1609004 TI - Changes to the National Physical Laboratory primary standards for x-ray exposure and air kerma. PMID- 1609005 TI - Shoulder injuries. AB - Shoulder injuries result from acute or repetitive over-use mechanisms. An outline for a careful history and physical examination is presented along with recommendations for radiographic imaging of shoulder injuries dependent on the suspected diagnosis and injury mechanism. Descriptions of the more common shoulder problems are presented with recommendations for non-surgical treatment. Indications for surgical treatment that will allow the primary practitioner to best manage these injuries are presented. PMID- 1609006 TI - Elbow injuries in athletes. AB - Most elbow injuries carry an excellent prognosis for return to a given sport. Early identification of overuse injuries and joint contractures can deter bone deformities in later life. Early evaluation can deter severe complications such as that of neurovascular injury. Rehabilitation should not be considered complete until there has been maximal restoration and correction of technique and accuracy in addition to the issue of soft-tissue healing. PMID- 1609007 TI - Patellar tracking problems in athletes. AB - Problems of the patellofemoral joint have long been recognized as a source of knee dysfunction. They range in spectrum from pain alone to recurrent instability, yet all are related in origin by congenital predisposition. Problems of the extensor mechanism are prevalent in any and all populations. Most patellofemoral problems respond readily to conservative rehabilitation efforts. Because of its chronic, recurrent nature, satisfactory results remain elusive in some syndromes. In our practice, the newer McConnell techniques have proved to be a positive addition to the extensor mechanism armamentarium, allowing pain-free return to function for most patients. PMID- 1609008 TI - Conservative management of patellofemoral dysfunction. AB - Treating PFD starts with a thorough evaluation so that an accurate diagnosis can be made and a specific treatment plan established. A standardized, cookbook treatment approach can be avoided by adapting each rehabilitation program to the patient's specific needs without creating additional symptoms. Although many different strengthening modes have been used over the years, current trends are oriented less toward strength of the quadriceps and VMO and more toward improving VMO control of the patella. Functional strengthening modes are replacing more traditional methods. Improved lateral retinacular mobility and muscular flexibility enhance tracking of the patella and this in turn is facilitory to the VMO. Patient awareness of symptoms throughout the rehabilitation process helps avoid inappropriate activities. Although the therapeutic exercise components are of primary importance, other adjunct treatments may also be helpful. Medication and icing may facilitate better VMO activity by controlling inflammation. Patellar taping assists patellar tracking, which provides for better patellofemoral stability and reduced mechanical stress. While EMS may provide some strengthening effect to weakened musculature, BFB provides the patient with a way to monitor and enhance their own exercise efforts and improve motor learning for functional activities. Education of the patient to the etiology, biomechanics, treatment, and prevention of PFD enhances the short-term acquisition of rehabilitation skills, long-term patterns of motor control, and provides a lasting knowledge base with which the patient can functionally progress with minimum symptoms. PMID- 1609009 TI - Traumatic knee injuries. AB - This article addresses the history and physical examination of traumatic knee injuries. The history should include differentiation between contact and non contact sports. An audible pop usually implies anterior cruciate ligament rupture. The examination should include a thorough physical examination, especially the Lachman's test and the pivot shift sign. Ligamentous and cartilaginous injuries and their treatment are outlined. PMID- 1609010 TI - Ankle injuries in athletes. AB - Ankle injuries are the most frequent cause of physician evaluation in a sports oriented environment. The lateral ligaments are most commonly injured. With a detailed history, physical and radiographic examination to avoid missing underlying pathology, the primary care physician can diagnose and treat the majority of ankle injuries. Occasionally, stress radiographs, arthograms, or magnetic resonance imaging (MRI) is needed. The vast majority of ankle sprains can be treated with adhesive tape strapping or semirigid orthotics and nonsteroidal anti-inflammatory medication followed by rehabilitation. Key points of rehabilitation are control of pain and swelling acutely with nonsteroidal anti inflammatories and RICE (rest, ice, compression, and elevation), then restoring normal range of motion, strengthening muscle groups, and retraining proprioception of the ankle joint. PMID- 1609011 TI - Dance injuries. AB - Dancers are athletes in an artistic setting. Their injuries, as in other sports, are acute and chronic. Usually, the acute problems are not severe but still can be devastating, especially to the career performer. Chronic problems abound, especially in the lumbosacral spine and lower extremities. Evaluating the dancer with an understanding of the technical and physical demands aids in their care. Treating this dedicated population can be rewarding, and one will find possibly no greater appreciation for one's efforts as a medical practitioner. PMID- 1609012 TI - Quality assessment in the medical intensive care unit. Continued evolution of a data model. AB - Quality assessment and assurance activities in the intensive care unit are complex processes that begin with the definition of the scope of services delivered in the unit with further identification of the important aspects of care. There is also a need to establish indicators of quality, gather data, and finally to organize the data into useful information. There are many approaches to these efforts ranging from establishment of indicators to data collection and analysis of patterns that lead to clarification of the indicators. We chose the latter pathway, specifically utilizing a previously described data model in which information was grouped according to structure, process, and outcome of patient care. In this paper, we focus on the application of the concept of patient days of service for quantification of the utilization of resources as an element of quality. Efficient utilization of resources cannot be effected until data on actual utilization are collected and analyzed. PMID- 1609013 TI - Potential conflicts of interest in the delivery of medical services: an analysis of the situation and a proposal. AB - One health care issue that has gained recent public and professional attention is that of professional conflicts of interest with regard to financial incentives to either withhold possibly necessary services or perform unnecessary ones. This essay explores the evidence bearing on the issue, interprets published information, and proposes a solution to deal with the issue. PMID- 1609014 TI - Measurement of dollar value of services in a capitated dental plan. AB - A number of attempts have been made to develop measures of the cost of resources expended to produce specific services that are more equitable than fees. Two conceptually different relative value methods (RVU and RTCU) and UCR fee-for service were used to measure the dollar value of care produced in three consecutive years under a network-type capitation dental plan. While each yielded a different total, the values were relatively close in the first year. However, they diverged in the second and third years even when an inflation factor was kept constant for all three. In addition, the dollar value of specific services varied markedly over the three methods. The relative merits of the different systems are discussed, as well as possible reasons for the divergence. It is concluded that the RTCU system is preferable, but that great care must be taken to keep any system current, regardless of specific derivation. PMID- 1609015 TI - Green Spring criteria for medical necessity of outpatient treatment and its use in a mental health utilization review program. AB - The authors have developed a two-tiered method for utilization review of outpatient mental health services. The methodology looks at initial and continued treatment evaluation and uses diagnosis, symptoms, plan of treatment, and the Global Assessment Scale (GAS) among other indicators to determine appropriateness of treatment. Preliminary program experience has been positive and is included. PMID- 1609016 TI - Cortisol in alcoholics with a disordered aggression control. AB - Considerable evidence exists that the limbic system and the hypothalamus play an important role in the HPA axis disturbances found in depressive disorders. Evidence also exists that the limbic system plays a role in the modulation of aggressive behavior. Yet the HPA function of individuals with a disordered regulation of aggression has received little scrutiny. Because aggressive behavior has been observed to be extensively correlated with heavy alcohol use, we explored the HPA function of alcoholics who had had a life-long history of violence. Basal 0700h cortisol was measured in 4 consecutive wk following cessation of drinking in 19 alcoholics with a history of depression, and 17 alcoholics with a history of violent behavior, eight of whom had been incarcerated because of the severity of their violent acts. When compared with alcoholics with no problem in mood or aggression regulation, significant cortisol increases were found in the group of patients who had been incarcerated for violent acts and not in any other group. This increase persisted for 4 wk after cessation of drinking. A variety of variables, including several measures of alcohol consumption, amounts of benzodiazepines used for detoxification, and liver function tests, failed to show significant associations with cortisol. Data are interpreted as indicating that individuals displaying severe forms of violence could have a dysregulated HPA function revealed by exposure to excessive amounts of alcohol. PMID- 1609017 TI - Creative musical behavior and sex hormones: musical talent and spatial ability in the two sexes. AB - Creative musical behavior, musical intelligence, and spatial ability were investigated in relation to salivary testosterone (T). In a cross-sectional study with 117 adults and in an 8-yr longitudinal study with 120 adolescents, composers, instrumentalists, and nonmusicians of both sexes were compared by analyses of variance. Results indicate that an optimal T range may exist for the expression of creative musical behavior. This range may be at the bottom of normal male T range and at the top of normal female T range. In addition, musicians were found to attain significantly higher spatial test scores than nonmusicians, both, in an 8-yr-period of adolescent development and in adulthood. PMID- 1609018 TI - Dose-dependent and time-related stimulus properties of LHRH in male but not in female rats. AB - Male and female rats (N = 32) were trained to discriminate 5 micrograms/kg LHRH from saline in a two-lever, food-reinforced drug discrimination procedure with injection-session intervals of 15 min or 45 min. When the interval was 15 min, neither males nor females were able to discriminate the stimulus conditions. With an interval of 45 min, LHRH showed sex-dependent stimulus properties. Male, but not female, rats reliably discriminated LHRH from saline within 50 training sessions. In males, generalization tests showed dose-dependent and time-related stimulus effects of LHRH (doses ranged from 62.5 ng/kg to 8 micrograms/kg, and intervals ranged from -15 min to -120 min). The results indicate that LHRH may be an essential part of the stimulus complex in male rats but could not gain control over operant behavior in female rats. PMID- 1609019 TI - Temporal relationship between melatonin and cortisol responses to nighttime physical stress in humans. AB - It has been shown that, in the rat, physical stress decreases pineal melatonin levels at night, whereas it increases melatonin production during the day. We have demonstrated that nighttime physical exercise is able to blunt the nocturnal surge of plasma melatonin in healthy subjects. Since this effect might be mediated by exercise-induced cortisol secretion from the adrenal gland, in the present investigation we studied the relationship between cortisol and melatonin responses to nighttime physical stress in six healthy men, aged 28-33 yr. The physical stress consisted of bicycling on a bicycle ergometer at 50% of personal maximum work capacity (MWC), followed by another 10 min of bicycling at 80% of MWC. According to our previous data, physical exercise performed between 2240 h and 2300 h significantly reduced the nocturnal surge of plasma melatonin and increased the levels of cortisol. The surge in plasma cortisol preceded the decrease in plasma melatonin concentration. These findings suggest a temporal relationship between plasma cortisol and melatonin responses to physical stress; the causal nature of this relationship remains to be elucidated. PMID- 1609020 TI - Autoimmune thyroid disease, left-handedness, and developmental dyslexia. AB - Autoimmune thyroid disease (ATD) (Graves' disease and Hashimoto's thyroiditis) has been one of a number of autoimmune diseases possibly associated with left handedness, mixed dominance, and learning disability. In the present study, 74 men with ATD were compared to 24 control men with non-ATD. An increased frequency of mixed dominance and traits suggestive of dyslexia were observed in the patients with ATD. These data are consistent with a link between the development of ATD and cerebral dominance. PMID- 1609021 TI - SPR Award, 1990. For distinguished contributions to psychophysiology: Peter J. Lang. PMID- 1609022 TI - Event related potentials and EEG components in a semantic memory search task. AB - This study examined the effects of memory search and related processes on both time and frequency domain components of electroencephalographic activity. More specifically, we were interested in the relationship between EEG and event related potential (ERP) components as a function of memory load and response type. Subjects performed a semantic memory search task in which they matched word probes to category labels. Consistent with previous studies, reaction time increased and accuracy decreased with increasing memory loads. A negative component of the ERP (N400) was found to reflect semantic mismatch: N400s were larger for the nontargets than for the targets. Two ERP components were found to be reciprocally related to memory load. P300 decreased and Negative Slow Wave increased in amplitude with increases in the size of the memory set. These two ERP components were reflected by different components in a Principal Components Analysis. The power in the theta band (5-7 Hz) also increased as a function of memory load and appears to be functionally and topographically related to the Negative Slow Wave in the ERP. It is argued that both measures are jointly determined and reflect the difficulty of the conceptual operations during memory search. PMID- 1609023 TI - Frequency-specific amplification of heart rate rhythms using oscillatory tilt. AB - Heart rate rhythms have been demonstrated to parallel specific psychological processes. Efficient experimental control of the amplitude of these rhythms would allow evaluation of bidirectional psychophysiological hypotheses. This experiment was performed to examine the specificity of the heart rate rhythm response to oscillatory head-up tilt. Seventy-one adults (36 male, 35 female) aged 18-30 were positioned on a tilt-table and oscillated at 0.08 Hz with a maximum tilt angle of +21 degrees for a 10-min period. Heart period, heart period variability at 0.08 Hz (i.e., Traube-Hering-Mayer (THM) variance), and respiratory sinus arrhythmia (quantified using vagal tone, V) were measured. For a subset of 21 subjects, continuous measures were derived to examine the response to onset of oscillatory tilt. Respiratory activity was also measured in these subjects. There was a significant increase in the amplitude of the THM variance during tilt stimulation. Tilt did not significantly change heart period, V, or respiration frequency. Following cessation of tilt, THM variance returned to baseline levels, heart period lengthened for males, and V increased for both sexes. Subjects with higher amplitude baseline V were characterized by more rapid THM variance response to tilt. Results suggest that parasympathetic tone moderates the THM variance increase elicited by low-frequency oscillatory tilt. PMID- 1609024 TI - Reliable measures of behaviorally-evoked cardiovascular reactivity from a PC based test battery: results from student and community samples. AB - This paper describes efforts to reduce measurement error in the assessment of cardiovascular reactivity by standardizing task requirements and by aggregating data across tasks and testing sessions. Using these methods, reliable measures of reactivity (.80 or greater) were obtained on five different measures of cardiovascular function (heart rate, systolic blood pressure, diastolic blood pressure, stroke volume, pre-ejection period) in samples of college students and community volunteers. Methodological limitations may have hampered previous efforts in this area. Current findings are consistent with a dispositional model of cardiovascular reactivity, and they suggest productive future strategies for obtaining reliable assessments. PMID- 1609025 TI - The effects of scopolamine on event-related potentials in a continuous recognition memory task. AB - Event-related potentials (ERPs) were recorded during a task requiring continuous recognition memory for visually-presented words. Twelve subjects each performed the task twice, once following the administration of scopolamine, and once after receiving a saline placebo. In the placebo condition, correctly detected "old" words (i.e., words that had been presented once before during the task) evoked more positive-going ERPs than did "new" words. Scopolamine caused a substantial impairment in task performance, but did not reduce the size of these old-word/new word ERP differences. It is concluded that old/new ERP effects are unlikely to reflect cholinergically-mediated neural activity underlying normal recognition memory. PMID- 1609026 TI - An electrophysiological study of semantic processing in young and middle-aged academics. AB - This study explored age differences in the N400 component, described by Kutas and Hillyard as an index of semantic expectancy. A group of young students and a group of middle-aged academics read a number of congruent and incongruent sentences followed by a recognition task. Age differences were found in both accuracy and speed in the recognition task. The N400 elicited in the reading task was both delayed in latency and reduced in amplitude in the older group. These aging effects could not be attributed to early stimulus input processes because the N1 did not differ between the age groups. A re-averaging of the event-related potentials during reading as a function of subsequent recognition showed a small memory-related positivity for the younger group and a large memory-related positivity for the older group, suggesting a difference in the encoding strategies of the two groups. To check the generalizability of the results of this particular age group, a further task (a memory scanning task) was carried out. The results, a delayed P3b and an increased reaction time, matched those found in the literature. PMID- 1609027 TI - A nonstationarity test for the spectral analysis of physiological time series with an application to respiratory sinus arrhythmia. AB - The spectral analysis of time series requires the signal to be at least weakly stationary; i.e., the mean, (co-) variance, and spectrum of the time series should not vary from segment to segment. It is commonly assumed that psychophysiological time series are not stationary. This study introduces a nonstationarity test to the psychophysiological literature, which is derived from evolutionary spectral analysis. Basically, the test consists of a double window technique in both the time and frequency domains, leading to a two-way analysis of variance for times and frequencies. In the current study, the nonstationarity test is applied to heart rate data obtained in a typical psychophysiological setting. Heart rate and respiration were measured in four age groups under four conditions--rest, paced breathing, vigilance, and reaction time. The results indicate that only few physiological time series were completely stationary. However, for every subject, and in every condition stationary stretches could be found that were long enough to apply spectral analysis. Spectral measures (power, coherence, and phase spectra) were then compared for stationary parts of the data and the total data. This comparison indicated that nonstationarity affects all spectral measures. Most importantly, Stationarity x Task Condition x Frequency Band interactions were observed for coherence and phase spectra, and there were significant interactions with age for each of the spectral indices. These findings suggest that nonstationarity may result in biased outcomes of significance tests of the effects of task manipulations on the spectral indices of cardiac time series. Thus, it was concluded that the stationarity test should be routinely applied in the spectral analysis of physiological time series. In addition, it was suggested that the nonstationarity test has an even wider range of application that might be of interest to the psychophysiologist. PMID- 1609028 TI - Breathing rhythms of the heart in a world of no steady state: a comment on Weber, Molenaar, and van der Molen. PMID- 1609029 TI - P300, food consumption, and memory performance. AB - The effects of food intake on the P300 (P3) component of the event-related brain potential (ERP) were assessed in two studies. Experiment 1 compared 24 subjects who had not eaten within 6 hours of testing with 24 subjects who had consumed food within 3 hours of testing. P3 target stimulus amplitude was reduced significantly for the subjects who had not eaten relative to those who had eaten, whereas peak P3 latency was only moderately affected by the recency of food consumption over task conditions. In Experiment 2, P3 measurements, memory performance in a word recall task, and blood glucose levels were obtained from 24 subjects at three different times: 1) after a 14-hour fast, 2) 5 min after consuming lunch, and 3) 30 min after consuming lunch. P3 target stimulus amplitude increased initially after food intake and decreased slightly at the third measurement time, while peak P3 latency became somewhat shorter immediately after food intake but then returned to baseline. Recall for recently presented items mimicked the P3 amplitude changes, whereas blood glucose levels increased monotonically across food conditions. The results from both studies suggest that: 1) target stimulus P3 amplitude is affected by the recency of food intake; 2) food-related P3 amplitude changes appear related to memory function; and 3) subjects should eat within several hours before ERPs are acquired to ensure that P3 component measurements reflect values indicative of normal bodily functioning. PMID- 1609030 TI - Reflex modification in psychosis-prone young adults. AB - The present study examined modification of the startle reflex in psychosis-prone and normal control subjects, using a continuous pure tone prestimulus (S1) and an intense white noise startle stimulus (S2). Reflex modification conditions consisted of stimulus pairs with onset asynchronies of 60, 120, and 2000 ms with a startle-alone condition as control. Startle was indexed by the eyeblink, which was measured by vertical electro-oculography. Subjects were identified as psychosis-prone by their high scores on the Perceptual Aberration or the Physical Anhedonia scales. Group differences in blink magnitude inhibition were observed between perceptual aberration and control subjects during short stimulus onset asynchronies, with perceptual aberrators showing significantly less inhibition than controls at 120 ms. No differences were evident between anhedonic and control subjects at the two short onset asynchronies nor were there any significant between-group differences when the interval between stimuli was long (2000 ms). These results suggest that subjects with perceptual aberrations may share with schizophrenics and other schizophrenia-spectrum subjects an underdeveloped mechanism which in normal subjects is presumed to operate during preattentive processing and functions to protect sensory information from the interfering effects of subsequent stimuli. PMID- 1609031 TI - P300 and individual differences: morning/evening activity preference, food, and time-of-day. AB - To determine how individual differences stemming from activity preference, previous food intake, and time-of-day affect the P300 or P3 event-related brain potential (ERP), subject groups who varied orthogonally on these factors were compared using a simple auditory discrimination task to elicit the ERPs. Amplitude of the P3 component for morning-preferring subjects who had eaten recently was relatively large for both the morning and evening measurement time groups. P3 amplitude for the morning-preferring subjects who had not eaten recently was large for those measured in the morning and relatively small for those subjects measured in the evening. For evening-preferring subjects who had eaten recently, P3 amplitude was again relatively large for both the morning and evening measurement time groups. Evening-preferring subjects who had not eaten recently produced very small P3 components for those measured in the morning compared to the large components produced by those subjects measured in the evening. P3 latency tended to be longer for all subjects who had not eaten recently compared to those who had. The results suggest that the P3 component is sensitive to physiological and psychological changes originating from individual differences related to bodily state, which perhaps stems from individual differences in arousal level. PMID- 1609033 TI - 31st annual meeting of the New Clinical Drug Evaluation Unit (NCDEU) program. Key Biscayne, Florida, May 28-31, 1991. PMID- 1609032 TI - Physiological arousal and perception of bodily state during parachute jumping. AB - Heart rate and respiration rate were recorded with a portable data recording system before and during a parachute jump in 36 male sport parachutists with differing degrees of experience. The recordings were analyzed at 12 psychologically relevant points in time along with the subjective ratings of physical arousal. Novice parachutists showed a higher degree of self-rated arousal during jumps. However, the two groups displayed nearly parallel curves for heart and respiration rates, differing significantly from each other only in the level of their respective heart rates. Furthermore, experienced jumpers seem to be better informed about their state of physiological arousal during the jump than are novice jumpers. These results do not confirm the proposed anxiety inhibition process, postulated by Epstein (1967). PMID- 1609035 TI - Buprenorphine: an alternative to methadone for heroin dependence treatment. AB - Eighty-five heroin addicts who were unwilling to receive methadone maintenance or enter therapeutic communities were assessed, single-blind, for the lowest sublingual dose of buprenorphine that blocked heroin craving (8.0 mg max). All doses were administered daily under observation. After maintenance for 4 to 12 weeks, abstinent subjects (confirmed by urine drug screens) entered a double blind discontinuation trial and were randomly assigned to receive dose reductions (10% twice weekly for 5 weeks to zero dose, then placebo for 2 weeks) or a stable dose for 7 weeks. Subjects were terminated from discontinuation if heroin was used or they had increased craving/symptoms. Subjects completed the trial if they did not use heroin and had no increase in craving/symptoms. A wide dose range (1.5-8.0 mg/day) was effective in reducing heroin craving and use. Of 73 subjects who received buprenorphine for 4 to 52 weeks, 40 had no prior treatment, despite high levels (mean $/day heroin = 70.5 +/- 94.7) and many years (mean years = 10.7 +/- 8.6) of dependence. Subjects who received dose reductions developed abstinence symptoms, low energy most commonly, associated with drug-seeking behavior. Discontinuation trial outcome (n = 51) shows a highly significant difference between 29 subjects who received dose reductions (28 terminated, 1 completed) and 22 subjects who received no dose reductions (3 terminated; 19 completed) (chi-square = 36.08; p less than .00001). The findings suggest that buprenorphine could be an important medication for reducing demand for heroin by many heroin addicts who remain outside the present health-care system.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609034 TI - Plasma prolactin and homovanillic acid as markers for psychopathology and abnormal movements after neuroleptic dose decrease. AB - Plasma prolactin concentration (pPRL), plasma homovanillic acid concentration (pHVA), and symptomatology were measured in 24 male subjects with schizophrenia during maintenance haloperidol treatment. Fourteen subjects subsequently underwent 50 percent dose decreases under placebo-controlled, double-blind conditions. At baseline, a significant inverse correlation was found between pPRL and both tardive dyskinesia (TD) and "thinking disorder"; pPRL was directly correlated with negative symptoms. No such relationship was found with pHVA. In the patients who underwent a dose decrease, no relationship was found between baseline pPRL or pHVA and any clinical variable after the decrease. These data do not support the use of baseline pPRL or pHVA as markers of central dopamine function subsequent to a neuroleptic dose decrease. PMID- 1609036 TI - Psychopharmacologic treatment of cocaine dependence. PMID- 1609037 TI - Buprenorphine for cocaine and opiate dependence. AB - Buprenorphine, a mixed opioid agonist/antagonist, has been examined not only for the treatment of opioid dependence, but also for concurrent dependence on both opioids and cocaine. Preliminary human studies have suggested that buprenorphine treatment may be associated with significantly less cocaine abuse than is treatment with methadone maintenance. Preclinical studies in both primates and rodents have also indicated that buprenorphine may reduce cocaine self administration and attenuate place preference for cocaine. Two double-blind, randomized clinical trials comparing buprenorphine with methadone have failed to demonstrate that buprenorphine is superior to methadone in reducing cocaine abuse. However, the trial by Kosten and associates has suggested a larger reduction in cocaine abuse at 6 mg than at 2 mg daily of buprenorphine. This dose dependence is consistent with cocaine challenge studies in which buprenorphine attenuated cocaine effects at 4 mg, but not at 2 mg, daily. PMID- 1609038 TI - A pilot trial of gepirone vs. placebo in the treatment of cocaine dependency. AB - An interim analysis of 41 evaluable patients compared gepirone to placebo treatment in a randomized, double-blind, 12-week study of cocaine dependence without opiate abuse. The response to gepirone at a mean dose of 16.25 mg/day did not differ from placebo by measures of time in study, positive urine cocaine screens (greater than 6 weeks), Clinical Global Impressions (CGI) Global Improvements Scale, Cocaine Craving Scale (CCS), Quantitative Cocaine Inventory (QCI), Addiction Severity Index (ASI), Global Assessment Scale (GAS), Hamilton Rating Scale for Depression (HAM-D), and Hamilton Anxiety Scale (HAM-A). Both treatment groups showed similar modest, average improvements during the study in all treatment measures. Adverse events were not treatment limiting. The following demographic and study measures suggested favorable trends for study outcomes: older age, divorced status, higher pre-treatment cocaine use, lower CCS scores, and lower self-reports of cocaine use according to QCI. PMID- 1609040 TI - Serotonin neuroscience discoveries usher in a new era of novel drug therapies for psychiatry. AB - Serotonin basic neuroscience discoveries are evolving at a very fast pace and are leading to innovations in clinical psychiatry and in drug development. Numerous novel pharmacological tools, each selective for a given serotonin receptor subtype, are being applied to several psychiatric disorders. The strategy employed is theory driven and hypothesis oriented, aiming for new drug development that selectively targets receptors that are rational sites for therapeutic actions. Thus, serotonin uptake inhibitors are targeting not only depression, but also obsessive-compulsive disorder (OCD). Serotonin1A agonists are targeting not only depression and anxiety, but also mixed anxiety depression. These and other agents selective for additional receptors are being tested in impulse control disorders; eating disorders; addictive disorders; and aggressive, violent, self-destructive, and suicidal behaviors. Serotonin research is an excellent example of how basic science discoveries in the 1990's "Decade of the Brain" are resulting in important advances in therapeutics for psychiatry. PMID- 1609039 TI - Definitions of secondary depression: effects on comorbidity and outcome in anxiety disorders. AB - The impact of different definitions of secondary depression on comorbidity and treatment outcome findings in anxiety disorder patients was examined by reviewing existing studies. Few data were found specifically on alternative definitions of secondary depression. However, other relevant findings yielded several conclusions: (a) different definitions of depression dramatically affect comorbidity findings, (b) widely divergent comorbidity findings are obtained in studies that use the same (temporal) definition of secondary depression, (c) few data exist on how different definitions of depression affect treatment outcome findings for anxiety disorders, and (d) some data show that patients' reports of whether or not their depressive symptoms temporally followed their anxiety symptoms are unreliable, suggesting that investigators who want to study secondary depression need to first determine that they have a reliable way to assess it. PMID- 1609041 TI - Modern cardiovascular standards for psychotropic drugs. AB - There has been a longstanding concern over the cardiovascular effects of antidepressant medication, originally prompted by the observation that patients who take overdoses of tricyclics most frequently die a cardiac death. This article (1) reviews the data on the cardiovascular effects of tricyclics, highlighting the methodological problems that plagued the early studies; (2) presents current techniques that are used in cardiovascular studies of psychotropic medication; and (3) discusses the problems of studying new nontricyclic drugs. Further, the article discusses some aspects of the complicated relationship between brain and heart function that are specifically relevant to whether there is inherent reason to believe that any drug that is effective as an antidepressant will necessarily affect cardiac function. PMID- 1609042 TI - Monoamine oxidase inhibitors: reversible and irreversible. AB - Coincident with and in part fueling advances in diagnostic nosology and drug development, the recent resurgence of interest in monoamine oxidase inhibitors (MAOIs) is reviewed. Accidentally discovered nearly 40 years ago as the first true antidepressants, the MAOIs soon fell into disfavor due to concerns about toxicity and seemingly lesser efficacy compared with the newer tricyclic compounds. Now that we have better understanding of the nature of the hypertensive and hyperpyrexic interactions of MAOIs with other substances, these medications have assumed a role in the treatment of nonendogenous depressive and anxiety syndromes, especially in operationally defined "atypical depression." The discovery of two MAO isoenzymes has resulted in a new generation of selective inhibitors in the search for enhanced efficacy (i.e., clorgyline) or safety (i.e., l-deprenyl). Most promising is the emerging class of reversible selective MAO-type A inhibitors, such as moclobemide, which combine antidepressant potency with freedom from the risk of dangerous tyramine-type adverse interactions. PMID- 1609043 TI - Developments in treatment of Alzheimer's disease. PMID- 1609044 TI - Effects of phosphatidylserine in Alzheimer's disease. AB - We studied 51 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients were treated for 12 weeks with a formulation of bovine cortex phosphatidylserine (BC-PS; 100 mg t.i.d.) or placebo, and those treated with the drug improved on several cognitive measures relative to those administered placebo. Differences between treatment groups were most apparent among patients with less severe cognitive impairment. Results suggest that phosphatidylserine may be a promising candidate for study in the early stages of AD. PMID- 1609045 TI - Noradrenergic intervention in Alzheimer's disease. AB - We report results of a double-blind, 13-week trial of the alpha2 noradrenergic agonist guanfacine in 29 patients meeting clinical criteria for probable Alzheimer's disease (AD). Patients studied were relatively young (mean = 71 years), well educated (mean = 13.5 years), and in the early stages of cognitive deterioration (mean Mini-Mental State score = 22). We found no evidence of improvement with a single .5-mg daily dose of guanfacine and some evidence of a modest negative effect of the drug on neuropsychological tests. We concluded that noradrenergic intervention alone is unlikely to be effective in Alzheimer's disease. PMID- 1609046 TI - Incidence and correlates of acute extrapyramidal symptoms in first episode of schizophrenia. AB - The incidence and correlates of extrapyramidal symptoms (EPS) in neuroleptic treatment of schizophrenic patients have been reported for chronic patients but not for first-episode patients. We examined the incidence and correlates of extrapyramidal symptoms in a cohort of 70 treatment-naive patients who received fluphenazine at 20-40 mg/day for the first 10 weeks of treatment. Thirty-four percent of our sample developed parkinsonism, 18 percent developed akathisia, and 36 percent developed dystonia. Acute EPS were associated with greater baseline psychopathology. Acute EPS were also associated with better treatment outcome in terms of time to and level of remission. These findings suggest that the EPS response of neuroleptic-naive patients may differ from that of chronically ill patients and that acute EPS status may be an indicator of pharmacologic responsivity in this group. PMID- 1609047 TI - High incidence of tardive dyskinesia in older outpatients on low doses of neuroleptics. AB - We are conducting a prospective study of tardive dyskinesia (TD) in psychiatric patients over age 45, a large proportion of whom have had less than 1 month of total lifetime neuroleptic exposure. Patients are treated with the lowest effective dose of either haloperidol (usually 1-3 mg daily) or thioridazine (usually 25-75 mg daily). Patients are reexamined 1 month and 3 months after initial assessment and then at 3-month intervals. To date, a total of 68 patients (mean age 69.5 years) have been evaluated. Survival analysis showed a 27 percent cumulative incidence of TD (the 95% confidence interval being 14% to 40%) with 6 months of neuroleptic treatment in the study. The TD and non-TD patients did not differ on demographic and baseline clinical measures. Instrumental assessment showed that a greater proportion of TD patients had subclinical evidence of dyskinesia prior to the institution of neuroleptics, compared with non-TD patients. PMID- 1609048 TI - Case-control studies of screening: a response to George Knox. PMID- 1609049 TI - Opportunistic 'catch-up' immunisation at entrant school medicals: parental attitudes and uptake. AB - The immunisation records of all 735 primary schoolchildren eligible for the entrant school medical examination in the Louth and District Unit were scrutinised for completion of primary and booster immunisations. Forty-six (6.26%) were identified as requiring one or more immunisations and, of these, just over half (52%) needed all (i.e. diphtheria, tetanus, polio, and MMR). Completion of prophylaxis was offered to the children at the time of their attendance for the routine entrant school medical No parents disapproved of the offer of immunisation as part of the entrant school medical. The additional school medical sessional time required to incorporate immunisation averaged at four minutes per child. Opportunistic immunisation at the entrant school medical was found to be acceptable both to parents and schools, and is an effective and efficient means of 'mopping up' incomplete primary and booster immunisations in districts where the overall uptakes are already high. PMID- 1609050 TI - Selective medicals at school entry. AB - This paper describes a selective procedure for use at school entry based on information from pre-school surveillance, parental questionnaires and class reviews. The pilot study in use over two years shows that the number of new conditions found at age 5 are relatively few in number and the extra time available can be used more appropriately for those with health problems affecting school progress. The job satisfaction for both nurses and doctors is increased and the parents are more fully involved with their child's health and progress. The introduction of a new computerised Child Health System and Parent Held Record will further enhance this system. PMID- 1609051 TI - Estimating the chance of an inadequately immunised child getting pertussis. AB - Before informed advice can be given to parents and health care workers about the need for pertussis immunisation, an estimate of the risk of inadequately immunised children contracting pertussis is needed. The study reported here was conducted because the literature contains no such estimates of risk. Analysis was made of a county's Notification of Disease Reports. Computation was carried out of age-specific annual notification rates of pertussis amongst adequately and inadequately immunised children. It was found that inadequately immunised one year-old children probably have more than a one in six chance of developing pertussis before age ten. PMID- 1609052 TI - Jarman index related to post-perinatal mortality. AB - Post-perinatal infant deaths in North and Southern Derbyshire District Health Authorities were calculated by electoral ward over a period of two years and related to Jarman scores of deprivation. The deaths were categorised into clinical-pathological groupings after full confidential enquiry. The post perinatal death rates were significantly related to Jarman score of deprivation. PMID- 1609053 TI - The prevalence of Toxocara canis ova in soil samples from parks and gardens in the London area. PMID- 1609054 TI - Health needs and all that. PMID- 1609055 TI - Food policy and public health. PMID- 1609056 TI - Relationship between DNA damage, DNA repair, metabolic state and cell lethality. AB - Induction of unrepairable DNA damage, accumulation of misrepaired DNA damage, and generation of imbalances in competing biochemical and/or metabolic processes have been proposed to explain the relationship between radiation-induced DNA damage and cell lethality. Theoretically, the temperature dependence of the critical DNA repair process(es) should be 1) either independent of or identical to the temperature dependence of cell killing if the first two hypotheses are correct, and 2) different if the third hypothesis is correct. To test this, exponentially growing rat 9L brain tumor cells were left at 37 degrees C or equilibrated for 3 14 h at 20 degrees C before irradiation. Cells were irradiated and allowed to repair at either 20 degrees C or 37 degrees C. Alternatively, the cells were irradiated at one of these temperatures and immediately shifted to the other temperature for repair. DNA damage was assessed by the alkaline elution technique; cell kill was assessed by a clonogenic assay. 9L cells maintained at 20 degrees C or 37 degrees C sustained the same amount of DNA damage as measured by alkaline elution. DNA repair instantaneously assumed the rate characteristic of the postirradiation temperature. For 9L cells equilibrated, irradiated, and repaired at 20 degrees C, the half-time of the fast phase of the DNA repair decreased by a factor of approximately 2 and the half-time of the slow phase decreased by a factor of approximately 5 over that measured in cells incubated, irradiated and repaired at 37 degrees C. Although the rate of DNA repair decreased substantially at 20 degrees C, the survival of 9L cells that were equilibrated and irradiated at 20 degrees C was greater (p less than 10(-4)) than those incubated and irradiated at 37 degrees C, when assayed by an immediate plating protocol. In addition, the survival of 9L cells equilibrated and irradiated at 20 degrees C and then shifted to 37 degrees C immediately after irradiation was greater (p less than 10(-2)) than that obtained with any other delayed plating protocol. Thus, the temperature dependence of the DNA repair processes measured by alkaline elution was different from the temperature dependence of cell killing measured either by an immediate or delayed plating protocol. These data support the hypothesis that many irradiated 9L tumor cells die because of imbalances in sets of competing biochemical and/or metabolic processes. PMID- 1609057 TI - Determination of some nuclear deoxyribonucleases in X-irradiated rat thymocytes. AB - The spectrum of nuclear nucleases in control and irradiated (4 Gy) thymocytes has been investigated. Using the method of SDS electrophoresis of nuclear proteins in 3H-DNA-polyacrylamide gels a number of polypeptides of MW. 35, 32, 17.7, 17.2 and 16.4 kDa possessing nuclease activity were found. The 35 kDa enzyme is only active in the presence of Ca2+ and Mg2+ ions. In response to cycloheximide injection (3 mg/100 g body weight) and irradiation, we did not detect the 35 kDa nuclease activity. Nucleases of 32, 17.7, 17.2 and 16.4 kDa are active in the presence of Ca2+ ions. The activities of these nucleases increases 60 min after irradiation. These nucleases were also found in the fraction of polydeoxyribonucleotide (PDN). PMID- 1609058 TI - Transfer factor of 131I from the fallout to human thyroid dose equivalent after the Chernobyl accident. AB - A similar pattern of variation with time in observed maxima of daily dose equivalent rates in human thyroids (TD - microSv.d-1) and of daily fallout radioactivities (FR - kBq.m-2) has been found after the Chernobyl accident. An estimate of the time-lag between the maxima in TD lines and the preceding FR peaks was made of about seven days for adult and nine days for juveniles. Applying this time-lag it was possible to estimate transfer factors from the fallout to thyroid dose equivalent: the highest estimated values were 221 microSv/kBq.m-2 for adult and 641 microSv/kBq.m-2 for juvenile thyroids. These values differ from those published by UNSCEAR (United Nations 1988), which have been calculated for various regions of Czechoslovakia, from ingestion and inhalation intake estimates. A broad variation of transfer factor values could be expected to result from such transfer calculations using ingestion and inhalation estimates. The findings also support the concept of a need for prolonged iodine prophylaxy after emissions of radioiodine into the environment. PMID- 1609059 TI - Chlorophyll fluorescence lifetime determination of waterstressed C3- and C4 plants. AB - This article describes the effect of water stress on the room temperature chlorophyll fluorescence lifetime of plants of wheat (C3) and maize (C4). In addition, net CO2 assimilation rate (PN), stomatal conductance and the fluorescence quenching coefficients qP and qNP at steady state conditions were recorded. The overall fluorescence decay of the control plants can be described by an average decay time of 1 ns for both plant types. Water stress did not modify this parameter in the case of wheat, whereas a shortening of the decay was observed for waterstressed maize plants (tau = 0.45 ns). This shortening in the chlorophyll fluorescence decay was accompanied by an increase in the non photochemical quenching (qNP). The photochemical quenching (qP) and therefore the electron transport via photosystem II remains unaffected by water stress. The most pronounced effect of the stress for both plant types was a decrease in PN due to a closure of the stomata. PMID- 1609060 TI - A CCD-OMA device for the measurement of complete chlorophyll fluorescence emission spectra of leaves during the fluorescence induction kinetics. AB - A new device for the measurement of complete laser induced fluorescence emission spectra (maxima near 690 and 735 nm) of leaves during the induction of the chlorophyll fluorescence is described. In this the excitation light (cw He/Ne laser, 632.8 nm) is switched on by a fast electro-mechanical shutter which provides an opening time of 1 ms. The emitted fluorescence is imaged onto the entrance slit of a multichannel spectrograph through a red cut-off filter (greater than 645 nm). A charge coupled device (CCD) sensor with 2048 elements simultaneously detects the complete chlorophyll fluorescence emission spectrum in the 650-800 nm wavelength range. Scanning is accomplished electronically and the integration time for a complete fluorescence emission spectrum can be selected from 10 ms up to 260 ms. Shutter, detector system and data acquisition are controlled by an IBM-PC/AT compatible computer. A maximum of 32 spectra can be measured at selected times during the fluorescence induction kinetics with the shortest time resolution of 10 ms. The instrument permits the determination of various fluorescence parameters: a) the rise-time of the fluorescence to the maximum level fm, b) the changes in the shape of the fluorescence emission spectra during the induction kinetics, c) the induction kinetics in the fluorescence ratio F690/F735 as well as d) the fluorescence decrease ratio Rfd at any wavelength between 650 to 800 nm. These fluorescence parameters provide information about the functioning of photosynthesis. The ratio F690/F735 allows the non-destructive determination of the chlorophyll content of leaves. The application of this instrument in ecophysiological research and stress physiology of plants is outlined. PMID- 1609061 TI - Probing DNA superstructure in human quiescent lymphocytes by X-ray-induced double strand breakage. AB - Human quiescent lymphocytes were lysed onto neutral sucrose gradients in order to sediment subsequently the nuclear DNA released within nucleoids. The position of nucleoids in the centrifuge tubes was detected fluorometrically by using the dye, ethidium bromide, and the height of the fluorescence peak was taken as a measure of DNA content. X-irradiation of lymphocytes, before their lysis, altered the DNA content of nucleoids and their sedimentation rate in accord with the view that (1) nuclear DNA is attached along its length at distances corresponding to 1.7 x 10(10) g/mol, and that (2) X-ray-induced double-strand breakage releases DNA fragments at random. Incubation at 37 degrees C of irradiated lymphocytes restored the amount of attached DNA as it would be expected from an intracellular repair process for DNA double-strand breaks. PMID- 1609062 TI - DNA damage and repair in chick embryo cells following X-irradiation in vitro as compared to mammalian cells--biochemical and physico-chemical investigations. AB - Brain cells (b-cells) and liver cells (l-cells) of the chicken embryo and thymic cells (t-cells) of the rat were X-irradiated in vitro at doses of 1.25-50 Gy. When compared to t-cells, b- and l-cells exhibited 1) a lower stimulation of poly (adenosine diphosphate-ribose) transferase and unscheduled DNA synthesis following X-irradiation, 2) an almost fivefold higher inhibition of semiconservative DNA synthesis, 3) a less condensed chromatin, 4) about fourfold higher threshold doses with regard to significant effects on nucleoid sedimentation and viscometry of alkaline cellular lysates, and 5) an apparently two- to threefold lower DNA repair during a 30 min post-exposure repair period. The results suggest that the lower radiation sensitivity of chicken embryo cells is attributable to an initial mechanism of DNA repair and/or DNA protection which may be closely connected to minor chromatin compactness and higher intrinsic activities of repair enzymes. PMID- 1609063 TI - Integrated imaging of adrenal disease. PMID- 1609064 TI - Chondrosarcomas of the skull base: MR imaging features. AB - The magnetic resonance (MR) images from 17 patients with chondrosarcomas of the skull base were retrospectively reviewed to characterize the size, location, signal intensity, and extension of these tumors. Eleven patients with chondrosarcomas received intravenously administered gadopentetate dimeglumine. In 16 patients, computed tomographic (CT) scans were obtained to evaluate intratumorous mineralization and bone erosion. On short repetition time (TR)/echo time (TE) MR images, chondrosarcomas generally had low to intermediate signal intensity; on long TR/TE MR images, they generally had very high signal intensity. Signal heterogeneity on long TR/TE MR images was seen in 10 of 17 tumors (59%) and was caused by matrix mineralization, fibrocartilaginous elements, or both. Matrix mineralization was demonstrated with CT in seven of the 16 chondrosarcomas. Chondrosarcomas showed marked enhancement after administration of gadopentetate dimeglumine in either a heterogeneous (n = 8) or homogeneous (n = 3) pattern. The information about the size and extent of these neoplasms was important in the choice of surgical approaches for gross total resection of tumor. PMID- 1609065 TI - High-resolution CT of the temporal bone: a modified baseline. AB - High-resolution computed tomography (CT) of the temporal bone, particularly axial scanning on a baseline parallel to the orbitomeatal line, produces radiation exposure to the patient's lenses. The authors evaluated the radiation dose to the lens and the visualization of temporal bone structures with use of scanning along the orbitomeatal line and on a line parallel to the hard palate. Evaluation of visualization was performed by five radiologists, with high-resolution CT scans of 45 healthy patients, and the chi 2 test was performed for comparison. The change of the baseline from the orbitomeatal line to a line parallel to the hard palate decreased the radiation dose to the lens from 12.7 cGy to 0.274 cGy and improved visualization of the stapes superstructure and the tympanic portion of the facial nerve canal, although visualization of the incus body, incudostapedial joint, lateral semicircular canal, and oval window was of equal quality. Therefore, the authors recommend a new baseline parallel to the hard palate for use at high-resolution CT of the temporal bone. PMID- 1609066 TI - Gantry angulation in brain CT: dosage implications, effect on posterior fossa artifacts, and current international practice. AB - The aim of this study was first to determine the effect of use of different scan planes at computed tomography (CT) of the brain on lens radiation dose and on severity of posterior fossa artifact. Twenty patients requiring nonenhanced and contrast material-enhanced brain CT scanning were selected. Each was scanned with two different beam angulations, one passing through the eyes and one avoiding them, and the resulting radiation doses were measured. Angling of the beam to avoid the orbit reduced the dose by 87%, while the severity of posterior fossa artifacts was not significantly different. Second, the implications of these results was assessed by means of an international questionnaire survey of current scanning technique. Only 32% of the respondents routinely avoided the eye during brain CT. No single scan plane was accepted by the respondents as being superior in terms of minimizing posterior fossa artifact. The authors conclude that the potential exists for a reduction in lens dose after reappraisal of radiologic practice in brain CT. PMID- 1609068 TI - Radiologists, communication, and Resolution 5: a medicolegal issue. AB - Resolution 5, adopted by the American College of Radiology, sets forth principles of direct communication that are important to every radiologist. This article reviews pertinent court decisions that affect radiologists and illustrates the importance of Resolution 5. In recent cases in state courts, liability standards have focused on four areas: negligence based on failure to personally inform clinicians of the diagnosis, ability of the jury to decide whether the radiologist's actions were appropriate, provision of information to the correct person, and necessity for expert testimony to define urgency. An important factor in liability cases appears to be the judgment of the radiologist in selection of the correct individual to receive the radiology report. The authors believe that electronic communication devices (eg, voice mail and fax machines) may potentially breach confidentiality and that such devices should therefore be used sparingly. Verbal communication by the radiologist to the referring physician, in addition to a written report, should avoid liability and improve quality of care for the patient. PMID- 1609067 TI - Delayed encephalopathy after acute carbon monoxide intoxication: MR imaging features and distribution of cerebral white matter lesions. AB - Magnetic resonance (MR) images obtained in 15 patients with delayed encephalopathy after acute carbon monoxide (CO) intoxication were reviewed. Images had been obtained 4-9 weeks after exposure to CO, during the relapse of neuropsychiatric symptoms after initial recovery. Bilateral symmetric confluent high signal intensity in the periventricular white matter and centrum semiovale was seen on long-repetition-time images (n = 15). The high intensity extended into the corpus callosum (n = 11), subcortical U fibers (n = 12), and external (n = 9) and internal (n = 7) capsules. Bilateral diffuse low-intensity signal in the thalamus and putamen on T2-weighted images, suggesting iron deposition, was demonstrated in 10 patients. Bilateral ischemia or necrosis of the globus pallidus was seen in nine patients. In three of four patients with follow-up MR imaging studies, a decrease in extent and signal intensity of white matter lesions accompanied lessening of clinical symptoms. These results suggest that the main pathologic feature of delayed encephalopathy associated with CO intoxication is a reversible demyelinating process of the cerebral white matter. PMID- 1609069 TI - Average radiation dose in standard CT examinations of the head: results of the 1990 NEXT survey. AB - In 1990, as part of the Nationwide Evaluation of X-ray Trends (NEXT) program, 252 computed tomographic (CT) systems were evaluated to measure radiation doses associated with standard head CT in adults. The multiple-scan average dose (MSAD) was used as the dose descriptor. For most of the systems, the MSAD at the midpoint on the central axis of a standard dosimetry phantom was between 34 and 55 mGy. Doses were as high as 140 mGy, and dose sometimes varied by a factor of two or more for identical CT units. This range indicates that dose can potentially be reduced by careful selection of standard CT techniques. Users of CT systems should be aware of radiation dose delivered with CT, dose ranges associated with different systems, and doses delivered with their particular unit, which requires that dose performance of CT systems be assessed by means of a protocol that allows comparison of data collected for identical and/or different units. PMID- 1609070 TI - Early detection of extravasation of radiographic contrast medium. Work in progress. AB - Microwave radiometry is a passive and noninvasive technique that allows quick detection of subcutaneous temperature changes. The feasibility of this technique for differentiating normal intravenous infusions of radiographic contrast medium from extravasations of contrast medium was tested in anesthetized dogs. Room temperature and heated ionic and nonionic contrast media were administered at flow rates ranging from 0.2 to 9.9 mL/sec by means of a power injector. On the basis of these experiments, an algorithm to adjust for extravasation detection thresholds as a function of injection flow rates was developed. With this algorithm, results showed a false-positive rate of 0% at all infusion rates and false-negative rates of 2%, 2%, and 4% at pump speeds of 0.2, 1.0, and 9.9 mL/sec, respectively. The times of these extravasation "alarms" corresponded to maximum extravasated volumes, respectively, of 4, 6.5, and 8 mL. Microwave radiometry has clinical potential for early detection of extravasation of contrast medium administered with power injectors. PMID- 1609071 TI - Use of informed consent for ionic and nonionic contrast media. AB - The use of informed consent before intravenous administration of contrast material remains a controversial issue. It involves explaining the risks of intravenous contrast material and obtaining the patient's permission for its use. All physician groups who had billed Pennsylvania Blue Shield for at least three intravenous contrast material-enhanced procedures performed in 1989 were surveyed. Informed consent was obtained from at least some patients by about two thirds of physician groups before using intravenous contrast material, regardless of whether it was ionic or nonionic. Nonradiologists were more likely to obtain informed consent before the use of ionic contrast material than radiologists. Regardless of specialty, practices associated with larger hospitals (greater than 250 beds), larger physician groups (greater than 10), or a university used informed consent less often than smaller physician groups or those associated with a smaller hospital or a private practice. Though results may be affected by regional variation or increased usage since previous surveys, the use of informed consent before the intravenous injection of contrast material is a common practice; it is obtained in the majority of patients. PMID- 1609072 TI - Radiology-assisted placement of implantable subcutaneous infusion ports for long term venous access. AB - Implantable infusion port devices are generally placed surgically. A technique for radiology-guided placement in adults is described, and the experience with 103 attempted port placements between June 1989 and October 1991 is analyzed. Placements were successful in 102 attempts (99%). Minor procedural difficulties occurred in six patients (5.9%). One major procedural complication (large hematoma) precluded port placement. Two patients were lost to follow-up after uncomplicated placements. There were four (4.0% of 100 patients) minor late complications. Major late complications requiring port removal occurred in 13 (13.0%): five suspected catheter-related infections, four catheter-related venous thromboses refractory to thrombolysis, and one each of wound dehiscence, formation of hematoma near the port, extraluminal migration of the catheter, and poor blood return. With a cumulative follow-up of 15,880 days (43.5 patient years) available, a rate of major complications of 13.6%, or 0.86% per 1,000 access days, is comparable to the rates of large surgical series. Radiology guided placement of infusion ports is safe and may offer advantages over surgical implantation. PMID- 1609073 TI - Radiographic evaluation of the wrist: what does the hand surgeon want to know? AB - Congenital, developmental, and acquired wrist deformities predispose patients to characteristic conditions and their associated debilities. The accurate recognition and quantitation of these conditions represent guideposts to treatment and prognosis. The authors present mensuration methods and normal ranges for the important morphologic features of carpal height, ulnar variance, radial inclination, radial length, palmar tilt, and radial shift. These measurements assume importance in the description and quantitation of many conditions. The authors review the radiographic features and diagnosis of dissociated and nondissociated carpal instability, scapholunate advanced collapse, ulnar translocation, ulnocarpal impaction, and ulnoradial impingement. PMID- 1609074 TI - Arterial injuries associated with complete dislocation of the knee. AB - To determine the frequency and type of arterial injuries associated with complete dislocation of the knee and to correlate the findings at physical examination with those at arteriography, a computerized search for patients with a diagnosis of dislocation of the knee at discharge from an urban trauma hospital was performed. Nineteen patients with complete dislocation of the knee were found. Arterial injuries were seen in six patients (32%). Four of the 19 patients had no pedal pulse at physical examination. In three of these four patients, occlusion of the popliteal artery was seen on arteriograms. The fourth patient had occlusion of an anomalous anterior tibial artery and a compartmental syndrome. Two of the 15 other patients with pedal pulses (13%) had nonoccluding intimal defects of the popliteal artery; these two patients did well without surgery. It is concluded that abnormal peripheral pulses associated with complete knee dislocation are highly predictive of major arterial injury. If peripheral pulses are normal, a low but definite frequency of arterial damage exists. PMID- 1609075 TI - Intrahepatic portal venous variations: prevalence with US. AB - A prospective ultrasound study was undertaken to determine the prevalence of variants of the intrahepatic branching of the portal venous system. Of the 507 patients examined, 55 (10.8%) had trifurcation, 24 (4.7%) had a right posterior segmental branch arising from the main portal vein, 22 (4.3%) had a right anterior segmental branch originating from the left portal vein, and one (0.2%) had absence of the horizontal segment of the left portal vein. Not one patient had complete absence of the right portal vein in this series. The remaining 405 (79.9%) patients had normal distribution of the portal venous system; some patients of the normal group had minor variations in distribution. PMID- 1609077 TI - Pulmonary embolism during compression US of the lower extremity. AB - To the author's knowledge, occurrence of pulmonary embolism during performance of compression ultrasound (US) of the lower extremity has not previously been reported in the radiology literature. The author describes a case in which pulmonary embolism was witnessed during compression US of venous thrombosis in a superficial femoral vein of a 64-year-old man. The embolism was documented with perfusion lung scanning. PMID- 1609078 TI - Simplified percutaneous gastrostomy. AB - By using 16-F self-retaining feeding catheters, fluoroscopically guided percutaneous gastrostomy was performed in 68 consecutive adult patients without the use of gastric fixation devices. Short-term (2-week) follow-up of all patients was available, with 30-day follow-up obtained in 94% of the study group (n = 64). Thirty-day mortality was 12%, with no procedure-related deaths. Major and minor morbidity rates were 4.7% and 7.8%, respectively. The mean procedure time was 7 minutes. These data compared favorably with those of series employing smaller catheters placed with and without the use of gastropexy, as well as surgical gastrostomy and gastropexy procedures. Percutaneous placement of large caliber (16-F) gastrostomy catheters is safe, effective, and rapid in the adult population and can be accomplished routinely without the use of prior gastropexy. PMID- 1609076 TI - Amelioration of cardiodepressive effects of gadopentetate dimeglumine with addition of ionic calcium. AB - Doses of gadopentetate dimeglumine of 0.1-0.5 mmol/kg cause cardiodepressive effects when injected as a rapid central bolus into the left jugular vein. This study evaluated the hemodynamic effects of this magnetic resonance imaging contrast medium with and without calcium supplementation in a rat model. Also, the potential of gadopentetate dimeglumine to bind ionized serum calcium was investigated in vitro. Addition of calcium ions resulted in dose-dependent attenuation of the hemodynamic depression induced by gadopentetate dimeglumine alone. The cardiodepressive response was negated for a 0.1-mmol/kg dose of the contrast agent by addition of 6 mumol/kg of calcium, for a 0.3-mmol/kg dose by addition of 12 mumol/kg of calcium, and for a 0.5-mmol/kg dose by addition of 18 mumol/kg of calcium. Concentrations of 2 and 4 mmol/L of gadopentetate dimeglumine were found to bind 5.1% and 10.1% of the ionized calcium in rat serum under in vitro conditions, respectively. PMID- 1609079 TI - Groin hernia: role of herniography. AB - To determine the value of herniography (also known as peritoneography) in the detection of groin hernias, herniographs obtained in 70 consecutive patients with clinically suspected hernias (but with a normal or inconclusive physical examination) were retrospectively evaluated. The radiologic features, complications, and final clinical outcome were reviewed. A total of 30 hernias were found. Sixteen patients underwent surgery; there were no false-positive herniographic diagnoses. No procedure-related complications occurred. These results indicate that herniography is a simple and valuable diagnostic tool in patients with unexplained groin pain or pain in the anterior abdominal wall, with an acceptably low complication rate. PMID- 1609080 TI - CT guidance for percutaneous gastrostomy and gastroenterostomy. AB - The authors describe the value of computed tomographic (CT) guidance for percutaneous gastrostomy (PG) or gastroenterostomy (PGE) in 22 patients with anatomic or pathologic difficulties precluding fluoroscopic guidance. Indications for PG or PGE were decompression for gastrointestinal obstruction (n = 15) or for feeding (n = 7). Thirteen patients previously underwent an unsuccessful attempt at or had been rejected as unsuitable for percutaneous endoscopic gastrostomy. CT guidance was selected because of inability to pass a nasogastric tube due to esophageal obstruction (n = 4), inability to tolerate gastric distention (n = 1), abnormal morphology in or around the stomach (n = 16), or simultaneous performance of a PG in one patient who was undergoing emergency CT-guided abscess drainage. Catheters were placed successfully in all 22 patients. No major complications occurred. CT is valuable for PG or PGE when anatomic or pathologic problems make fluoroscopic or endoscopic puncture unsafe or impossible. PMID- 1609081 TI - Hepatobiliary enhancement with Gd-EOB-DTPA: comparison of spin-echo and STIR imaging for detection of experimental liver metastases. AB - Gadolinium (4S)-4-(4-ethoxybenzyl)-3,6,9-tris(carboxylatomethyl)-3,6,9- triazaundecandioic acid-disodium salt (EOB-DTPA) ethoxybenzyl is a new hepatobiliary magnetic resonance (MR) contrast agent with dual elimination: 75% through the liver and bile and 25% through the kidneys in normal rats. In this study, Gd-EOB-DTPA was evaluated in a rodent model of metastatic liver disease to measure both relative enhancement and lesion-to-liver contrast. A secondary goal was to compare the relative performance of spin-echo (SE) and short inversion time inversion-recovery (STIR) imaging to demonstrate enhancement with Gd-EOB DTPA. After administration of 0.1 mmol of Gd-EOB-DTPA per kilogram, liver signal increased (positive enhancement) more than 200% with the use of the SE technique and declined (negative enhancement) by more than 80% with use of the STIR technique. Only minimal enhancement of implanted liver tumor was observed. Unlike the tumor, the gall-bladder and lumen of the duodenum were progressively enhanced over time. The lesion-to-liver contrast increased by approximately 500% with both the SE and STIR techniques after administration of Gd-EOB-DTPA. PMID- 1609082 TI - Small bowel stricture caused by rheumatoid vasculitis. AB - Small bowel involvement in rheumatoid arthritis is rare and is caused by vasculitis, which results in ulceration, perforation, and necrosis of the small bowel. The authors present a case of rheumatoid vasculitis associated with a small bowel stricture. The patient had a 3-week history of daily postprandial bloating, abdominal cramping, and vomiting. Barium study demonstrated partial small bowel obstruction. Pathologic examination of a resected segment of the small bowel proved that the stricture was caused by rheumatoid vasculitis. To the authors' knowledge, this is the first reported case of such an association in the radiology literature. PMID- 1609083 TI - Age-associated changes of the triangular fibrocartilage of the wrist: evaluation of the diagnostic performance of MR imaging. AB - To define the appearance of degenerative changes of the triangular fibrocartilage (TFC) of the wrist on magnetic resonance (MR) images, the TFCs in one wrist of each of 30 healthy subjects in three age groups (20-35, 36-50, and greater than 50 years) and six TFCs from fresh cadavers were examined by means of coronal T1 weighted spin-echo sequences. Histologic findings were compared with findings on MR images in the cadaveric TFCs. It was proved that patches or lines of signal hyperintensity within the cadaveric TFCs were caused by degenerative changes and tears. Similar changes of the TFCs on MR images of the healthy subjects may have been caused by degeneration. In the healthy subjects, degenerative changes of the TFC, usually well defined on MR images, occurred at a very early age. The TFC appears to undergo stages of degeneration comparable to those of the menisci of the knee, but differentiation between traumatic and degenerative tears may be difficult. PMID- 1609084 TI - Meniscal changes in the elderly: correlation of MR imaging and histologic findings. AB - In elderly patients, degenerative changes of the meniscus are common and may mimic a tear. The magnetic resonance (MR) image findings of 179 meniscal sections in 20 cadaver knees were correlated with the histologic and gross pathologic findings. The sensitivity of standard T1-weighted spin-echo images and their corresponding meniscal windows in depicting meniscal tears was 80.6%, specificity was 72.4%, and accuracy was 76.7%. These results are not as good as results reported previously. A major difficulty is the occurrence of grade 3 meniscal signal intensity and diffuse intrameniscal signal intensity in torn and intact menisci. MR imaging in elderly patients, however, is still useful in the diagnosis of meniscal abnormalities. Normal low signal intensity depicted within a meniscus at MR imaging and changes in grades 1 and 2 intrameniscal signal intensity are reliable signs of an intact meniscal surface. Grade 3 and diffuse meniscal signal intensities do not allow a specific diagnosis; menisci with these characteristics should be described as degenerated with a high probability of a tear. PMID- 1609085 TI - Swollen lower extremity: role of MR imaging. AB - The authors assessed the use of magnetic resonance imaging in differentiating lymphedema, phlebedema, and lipedema of the lower limb. They examined 14 patients: five with lipedema, five with lymphedema, and four with phlebedema. T1- and T2-weighted transaxial sequences were performed before administration of gadolinium tetraazacyclododecane-tetraacetic acid (DOTA) and T1-weighted spin echo sequences were performed after administration of Gd-DOTA in each patient. Images of patients with lipedema showed homogeneously enlarged subcutaneous layers, with no increase in signal intensity at T2-weighted imaging or after Gd DOTA administration. Patients with phlebedema had areas containing increased amounts of fluid within muscle and subcutaneous fat. In lymphedema, a honeycomb pattern above the fascia between muscle and subcutis was observed, with a marked increase in signal intensity at T2-weighted imaging. After Gd-DOTA administration, there was only a slight increase in signal intensity in the subcutis in lymphedema and phlebedema and a moderate increase in signal intensity in muscle in phlebedema. PMID- 1609086 TI - Giant cell tumor in skeletally immature patients. AB - The radiographs and clinical and surgical histories of 50 skeletally immature patients with histologically verified giant cell tumor (GCT) of the long and short tubular bones were retrospectively studied to determine the prevalence, location within bone (eg, epiphysis, metaphysis), skeletal distribution, radiographic appearance, and pathogenesis of GCTs. Skeletal immaturity was determined radiographically by the presence of open epiphyses. Patients were selected from a group of 876 patients who were seen in consultation with documented GCT of the tubular bones. Approximately 5.7% of all GCTs occurred in the skeletally immature (this rate must be viewed with caution due to the selection bias inherent in any referral population). The lesions almost invariably involved the metaphysis. The tibia was the most commonly affected site, representing approximately 26% of cases. All were geographic lytic lesions, with margins ranging from sclerotic to ill defined. An expanded (widened), remodeled bone contour was frequently encountered. Approximately 56% of lesions were solid or solid with cystic change; the remaining 44% were predominantly cystic. PMID- 1609087 TI - Epi- and metaphyseal changes in children caused by administration of bisphosphonates. AB - Nitrogen-containing bisphosphonates (NCBs) are potent inhibitors of bone resorption and are used in the treatment of adults with various skeletal disorders. Little is known about their effects on the growing skeleton. The authors retrospectively studied the skeletal radiographs obtained in nine children before, during, and after NCB administration. Bandlike metaphyseal sclerosis and concentric epi- and apophyseal sclerosis developed in all patients. The extent of sclerosis depended on the duration of treatment and was related to local, and probably general, skeletal growth activity. In the maturing spine, NCBs caused a "picture-frame" or "bone-within-bone" appearance, depending on continuation or cessation of administration. In addition, metaphyseal undertubulation of long bones was noted in five patients. After discontinuation of bisphosphonate treatment and/or closure of the growth plates, the degree of sclerosis decreased, and sclerosis tended to disappear, indicating that this is a reversible phenomenon. PMID- 1609088 TI - Dashed hopes for MR imaging of the head and neck: the power of the needle. PMID- 1609089 TI - M-mode sonography of the caudal spinal cord in patients with meningomyelocele. Work in progress. AB - The authors prospectively studied movement patterns of the spinal cord in 46 patients (aged 0.5-16 years) with meningomyelocele but without major neurologic deficits. Three different motion patients were observed. Reduced mobility correlated with a higher risk of developing secondary tethered cord syndrome after a mean observation time of 15 months. This technique may be helpful in identifying patients for early surgery. PMID- 1609091 TI - Percutaneous abscess drainage. PMID- 1609090 TI - Base-of-tongue cancer treated with external beam irradiation plus brachytherapy: oncologic and functional outcome. AB - Between January 1981 and June 1990, 36 previously untreated patients with squamous cancer of the base of the tongue were treated with radiation therapy. This therapy consisted of a 5,000-5,400-cGy external beam plus a 2,000-3,000-cGy boost to the base of the tongue with an iridium-192 implant. Necks with negative nodes were only irradiated, while necks with positive nodes were treated with irradiation plus neck dissection. Actuarial local control and survival at 2 years were 87.5%. Neck control was achieved in 35 of 36 patients. When implantation was performed with the nonlooping technique, the injury rate was statistically higher than in patients who underwent implantation with the looping technique (P = .02). Thirty patients participated in a function assessment involving a Performance Status Scale for patients with head and neck cancer. The authors concluded that management of base-of-tongue cancer with external beam irradiation plus brachytherapy is both oncologically and functionally successful. PMID- 1609092 TI - Three-dimensional viewing of and dosimetric calculations in Au-198 implants of the prostate. AB - A three-dimensional system for dosimetric calculation of radiation from interstitial brachytherapeutic implants was developed and was compared with conventional dosimetry performed with a commercial two-dimensional system. Software programs written for this study enabled the authors to place radioactive sources in the correct reconstructed anatomic locations, compute the isodose distribution around these sources, and display the isodose curves in their correct relationship to anatomic structures. Eight radiation oncologists evaluated the usefulness of both systems. Verification studies in phantoms and in 20 patients with gold-198 implants in the prostate gland showed that the experimental system was very accurate in volume reconstruction, seed localization, isodose distribution, point-dose calculation, and computation of dose-volume histograms. Although the dose depictions in the two systems matched almost exactly, statistically significant differences existed in interpretation of the dosimetric data generated by both systems. For example, the oncologists consistently believed that the dose to the prostate was lower when the three dimensional system was used (P less than or equal to .0001). PMID- 1609093 TI - Color Doppler-US guidance in transjugular placement of intrahepatic portosystemic shunts. AB - Percutaneous placement of portosystemic shunts requires access to the portal system from a transjugular approach. Color Doppler sonography was used to direct the transjugular puncture in intrahepatic portosystemic shunt procedures in four patients. In each case, the technique allowed quick, safe transjugular puncture of the portal vein and close real-time monitoring of the procedure. PMID- 1609094 TI - Device for facilitating precise alignment in bedside radiography. AB - The difficulty associated with achieving precise alignment in a bedside radiographic setting has led many departments to abandon the use of a grid and forfeit the improved contrast it affords. The authors describe a method of alignment that has proved successful in overcoming the hazards of grid cut-off in a bedside setting. The method affords obtainment of reproducible high-quality bedside radiographs with a 10:1 linear grid. PMID- 1609095 TI - Phantom for use in lung biopsy training. AB - A phantom to assist in the teaching of fluoroscopically guided transthoracic needle biopsy of pulmonary lesions was designed. The phantom was constructed of an aluminum and rubber skeleton, wood hemidiaphragms and heart, and foam rubber lungs and was covered with foam rubber. Modeling clay was used to simulate lesions. The authors believe the phantom is of value in helping increase the confidence and proficiency of the radiologist during the first few biopsy procedures with an actual patient. PMID- 1609096 TI - Screening mammography: who will meet the need? PMID- 1609097 TI - The urogram: are rumors of its death premature? PMID- 1609098 TI - Management of renal colic: redefining the role of the urogram. PMID- 1609099 TI - Statistical analysis with receiver operating characteristic curves. PMID- 1609100 TI - Improvement in mammography interpretation skills in a community radiology practice after dedicated teaching courses: 2-year medical audit of 38,633 cases. AB - The authors conducted a complete audit of results of 38,633 mammographic examinations performed by 12 general radiologists during a 2-year period with a computerized reporting system. During this period, 11 group members attended 17 dedicated mammography courses. Audit results were analyzed for each radiologist and the entire group. In the 2nd year, the number of breast cancers diagnosed increased 50% (from 121 to 181), with a 6.5% increase in patient volume. Sensitivity increased from 80% to 87%, and there was no change in the positive predictive value of 32%. Median tumor size and node positivity decreased. Most major variables of population and technical factors were unchanged. Diagnostic approach was altered during the 2nd year, as shown by a 50% increase in the use of spot compression, magnification views, and sonography. Analysis of each radiologist's performance before and after attending mammography courses showed similar changes. These data suggest that dedicated mammography courses can help improve radiologists' performance and alter their interpretive approach. PMID- 1609101 TI - Mammographic unit compression force: acceptance test and quality control protocols. AB - Firm compression of the breast in screen-film mammography procedures lowers the radiation dose to patients, enhances image contrast and definition, and improves visibility of pathologic conditions. Most mammography unit compression systems have no force-level indicator. Some systems show force variations with time and others, with angle and region of the compression device. Still other systems give poorly reproducible compression-force levels, and in one unit the force release mechanism jammed repeatedly. Detailed procedures for initial acceptance testing and continuing quality control checks are listed. Recommended measurements include levels of manual and automatic applied force, stability, reproducibility, and dependence on angulation and breast size and evaluation of operation of release mechanisms. Also necessary are observations of the condition and operation of the compression system. Test equipment is described and measurement frequency is specified, as well as suggested tolerance limits. Manufacturers of mammographic units are urged to build in compression-force gauges and to provide both a manual mode and a variable-force automatic mode. PMID- 1609102 TI - Fine-needle aspiration cytology in the detection of breast cancer in nonsuspicious lesions. AB - In 1988, fine-needle aspiration cytology (FNAC) was performed on 222 consecutive patients who underwent screening mammography and had benign-appearing opacities. FNAC was also performed in 2,248 consecutive symptomatic patients with clinically palpable masses and mammograms that were considered within normal limits. FNAC, performed with a 23-gauge needle, helped detect three unsuspected cancers in the 222 screened patients and eight unsuspected malignancies in the 2,248 symptomatic patients. Only one of every 225 nonsuspicious masses proved to be malignant, but, without FNAC, there would have been no way to know which mass was a newly surfacing carcinoma. FNAC not only helped detect early cancers, but its negative findings resulted in sparing patients the ordeal of surgical biopsy for benign conditions. The low lymph node metastatic rate of 18% suggests that patients with FNAC-depicted cancers have a prognosis as promising as those patients with mammographically detected malignancies. PMID- 1609103 TI - Factors influencing women to undergo screening mammography. AB - Despite the fact that mammography is a valuable tool for early detection of breast cancer, the majority of age-eligible American women do not avail themselves of screening mammography. To better understand why women do or do not undergo mammography and to further develop guidelines for promoting breast cancer screening, the authors investigated what impact personal factors, attitudes, and health-related behaviors have on compliance with screening mammography by surveying 521 women for information related to health behavior, health concerns, sense of well-being, satisfaction with health care, and knowledge about breast cancer. Women who underwent mammography were more likely to have a regular physician, to practice breast self-examination, to be less concerned over the cost of mammography, to be generally satisfied with their health care, to believe they have a greater sense of control over their health, and to be more knowledgeable about mammography and breast cancer. Age, health behavior, sense of well-being, locus of control, and breast cancer experience helped differentiate between women who had undergone mammography and those who had not. PMID- 1609104 TI - Posttransplant lymphoproliferative disorder: intrathoracic manifestations. AB - Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of organ transplantation and immunosuppression. Early diagnosis and treatment greatly affect prognosis. Chest radiographs (n = 13), chest computed tomographic (CT) scans (n = 2), or both (n = 20) from 35 patients with intrathoracic PTLD were retrospectively studied to define the intrathoracic manifestations of this disorder. Intrathoracic abnormalities consisted of pulmonary nodules (16 patients), patchy air-space consolidation (three patients), mediastinal and hilar adenopathy (17 patients), thymic enlargement (two patients), pericardial thickening and/or effusions (two patients), and pleural effusions (four patients). Multiple, well-circumscribed pulmonary nodules with or without mediastinal adenopathy are highly suggestive of PTLD. However, pathologic examination is usually necessary for a definitive diagnosis. PMID- 1609105 TI - Thymoma mimicking a thyroid mass. AB - Two cases of ectopic cervical thymoma are presented. These cases both manifested as mass lesions at the thoracic inlet, displacing the trachea, and were originally misdiagnosed as thyroid masses. The masses had clinical features similar to those previously reported for cervical thymoma: preponderance in women, benign clinical course, and absence of myasthenic symptoms. PMID- 1609106 TI - Impact of hard-copy size on observer performance in digital chest radiography. AB - To determine the impact of reduced hard-copy size on diagnostic performance of digital radiography, screen-film chest radiographs were compared with isodose digital storage phosphor radiographs in the detection of simulated nodules, fine pulmonary lines, and micronodular opacities superimposed on the chests of 10 healthy volunteers. Digital radiographs were laser-printed in a full-size conventional format and in image lengths of two-thirds, one-half, and five elevenths of the conventional format. Eighteen thousand observations by eight radiologists were analyzed by use of receiver operating characteristics. The detectability of lines and micronodular opacities decreased with declining image format size. In the detection of micronodular opacities, only the nearly full size digital images were equivalent to conventional images. In the detection of linear opacities, reduction of image length by one-half or more reduced performance (analysis of variance, P less than .05). Only for the detection of nodules was no major difference found. PMID- 1609107 TI - Renal colic: diagnosis and outcome. AB - To assess whether ultrasonography (US) with or without plain abdominal radiography (kidney, ureter, bladder [KUB] radiography) can replace intravenous urography (IVU) in detection of acute urinary tract obstruction, 101 consecutive patients with renal colic were evaluated with US followed immediately by IVU. Receiver operating characteristic (ROC) curves for US diagnosis of acute urinary tract obstruction yielded sensitivities of 91% and 92% for two reviewers at a specificity of 90%. There was no statistically significant difference between US and IVU results. When US was combined with KUB radiography, ROC curves yielded sensitivities of 94% and 97% for two reviewers at a specificity of 90%.KUB radiography alone was of limited diagnostic value. For US alone, no false positive results occurred, and the false-negative results (n = 9 and n = 6 for two reviewers) were encountered in cases of grade 1 hydronephrosis and nondilated obstructive uropathy. The authors conclude that US combined with KUB radiography can replace IVU in initial evaluation and follow-up of the great majority of patients with renal colic. PMID- 1609109 TI - Mechanisms of resistance to quinolones. PMID- 1609108 TI - Cervical cancer: serial MR imaging before and after primary radiation therapy--a 2-year follow-up study. AB - Serial magnetic resonance imaging studies were performed in 28 patients undergoing primary radiation therapy for invasive cervical cancer. T2-weighted spin-echo pulse sequences with long repetition times (2,500 msec) and echo times (30-100 msec) were used at a field strength of 1.5 T. Eighteen tumors responded promptly to radiation therapy with a volume reduction and significant decrease of signal intensity in the early posttreatment phase (1-3 months) and with total tumor regression at 1-6 months (immediate responders). At 6 months seven tumors were visible as residual tumors with declining signal intensity; all seven of these tumors had resolved at 9 months (delayed responders). Thus, a delayed response with residual tumor at 6 months was still compatible with subsequent clinical cure. The tumors showed progression and no marked change in signal intensity (nonresponders). Primary tumors with a volume of more than 50 cm3 were more likely to have no or delayed response. An early (2-3 months) and significant decrease in the signal intensity and volume of a tumor indicates a favorable response. Large primary tumors may show a delayed response. PMID- 1609110 TI - History of quinolone antibacterials. PMID- 1609112 TI - Future prospects of quinolones. PMID- 1609113 TI - Immunoregulatory role of neuropeptides. PMID- 1609111 TI - Adverse effects of fluoroquinolones. AB - The newer fluoroquinolones have various kinds of adverse reactions and drug-drug interactions. Patients given concurrent therapy of fluoroquinolones with theophylline should be carefully observed. It is better to avoid concurrent therapy of fluoroquinolones with NSAIDs, and patients given fluoroquinolones who have a history of central nervous system disorders should be put under careful observation, because of the possibility of central nervous system reactions. Fluoroquinolones should be carefully administered to patients with compromised renal functions, because fluoroquinolones are accumulated in patients with impaired renal function. Although fluoroquinolones have various kinds of adverse reactions, the frequency of toxicity is considered to be acceptable. However careful, clinical and experimental studies should be continued to reveal more details on the adverse reactions of fluoroquinolones. PMID- 1609114 TI - The new generation of monoamine oxidase inhibitors. AB - Irreversible and unspecific inhibitors of MAO were the first modern antidepressants, but after an initial success they fell into discredit due to adverse side effects. In the past two decades interest in MAO inhibitors has been renewed because of progress in basic research, a milestone being the finding that there are two subtypes of MAO, MAO-A and MAO-B. These are distinct proteins with high amino acid homology, coded by separate genes both located on the short arm of the human chromosome X. The enzyme subforms show different substrate specificities in vitro and different distributions within the central nervous system and in peripheral organs. In the central nervous system of man MAO-A seems to be mainly involved in the metabolism of 5 HT and noradrenaline, whereas 2 phenylethylamine and probably dopamine are predominantly deaminated by MAO-B. In the intestinal tract tyramine is mainly metabolized by MAO-A. These characteristics indicate distinct physiological functions of the two MAO subforms. Several irreversible and reversible non-hydrazine inhibitors with relative selectivities for one of the MAO-subforms have been developed. They belong to various chemical classes with different modes of enzyme inhibition. These range from covalent mechanism based interaction (e.g. by propargyl- and allylamine derivatives) to pseudosubstrate inhibition (e.g. by 2-aminoethyl carboxamides) and non-covalent interaction (e.g. by brofaromine, toloxatone and possibly moclobemide). The most important pharmacological effects of the new types of MAO inhibitors are those observed in neuropsychiatric disorders. The inhibitors of MAO-A show a favorable action in various forms of mental depression. The drugs seem to have about the same activity as other types of antidepressants, including tricyclic and related compounds as well as classical MAO inhibitors. The onset of action of the MAO-A inhibitors is claimed to be relatively fast. Other possible indications of these drugs include disorders with cognitive impairment, e.g. dementia of the Alzheimer type. In subjects with Parkinson's disease the MAO-B inhibitor L-deprenyl exerts a L-dopa-sparing effect, prolongs L-dopa action and seems to have a favorable influence regarding on-off disabilities. The action is in general transitory (months to several years). In addition L-deprenyl has been shown to delay the necessity for L-dopa treatment in patients with early parkinsonism. Whether the drug influence the progression of the disease is still a matter of debate. L-deprenyl also appears to have some antidepressant effect (especially in higher doses) and to exert a beneficial influence in other disorders, e.g. dementia of the Alzheimer type.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1609115 TI - In vitro properties of the newer quinolones. AB - Table 5 summarizes the activity of the newer quinolones against various bacteria including intracellular bacteria and the other microorganisms. In this table, the overall MIC ranges of NFLX, ENX, OFLX, and CPFX, for susceptible isolates of each bacteria are schematically presented. The newer quinolones are considered to have sufficient activity against gram-negative enteric bacteria, N. gonorrhoeae, and H. influenzae and Legionella spp. Since OFLX and CPFX show only moderate activity against staphylococci, streptococci, and P. aeruginosa, improvement is expected. As shown in Table 3, TFLX and the recent investigational quinolones such as SPFX and KB-5246 show higher and promising activity against gram-positive bacteria. However, further studies are needed with longer periods to indicate whether these newer agents will be able to stop the increase of quinolone-resistant staphylococci. Furthermore, the activity of the newer quinolones against obligate anaerobes such as clostridia and bacteroides are considered to be insufficient for clinical use. Whether it will be possible to synthesize quinolones with anti anaerobic activity sufficiently for clinical treatment is uncertain. Although Mycobacterium tuberculosis is susceptible to the newer quinolones, other mycobacteria are somewhat less susceptible to this class of agents. In addition, the newer quinolones have adequate activity against mycoplasma, chlamydia and rickettsia. From a microbiological viewpoint the prospects for the newer quinolones would be primarily to find agents that have higher anti-staphylococcal and anti-streptococcal activity. Secondly, agents possessing superior activity against obligate anaerobes such as Bacteroides spp. and Clostridium spp. are expected to synthesize. Furthermore, it may be possible to synthesize compounds that are sufficiently active for clinical use against atypical mycoplasma, chlamydia, and rickettsia. PMID- 1609116 TI - New quinolones--in vivo antibacterial activity. PMID- 1609117 TI - Pharmacokinetic aspects of newer quinolones. PMID- 1609118 TI - Recent advances in structure activity relationships in new quinolones. PMID- 1609119 TI - A quantitative solid-phase enzymeimmunoassay for 13,14-dihydro-15-keto- prostaglandin F2 alpha in plasma. AB - Enzymeimmunoassays (EIA) can be viable alternatives to radioimmunoassays (RIA). Indeed, from an environmental perspective, EIA are preferable to RIA. Therefore, the purpose of this project was to develop a quantitative EIA for 13,14-dihydro 15-keto-prostaglandin F2 alpha (PGFM) in bovine plasma. Acetylcholine esterase bound covalently to PGFM, rabbit anti-PGFM, mouse monoclonal anti-rabbit IgG, and PGFM were the principle reagents used for the EIA. Validation experiments indicated that: 1) PGFM standard curves, with doses ranging from 391 to 200,000 fg per microtiter well, were linear; 2) assay sensitivity averaged 391 fg per well; 3) for satisfactory results, PGFM had to be extracted from plasma; 4) content of PGFM in ethyl ether extracts of aliquots from serial dilutions of whole plasma with unknown amounts of PGFM and charcoal-stripped plasma supplemented with known amounts of PGFM did not deviate from parallelism with PGFM standard curves in buffer; 5) correlation between EIA and RIA measurements of PGFM in the same plasma samples was .95; 6) the regression of EIA data on RIA data was linear (Y = .93 x + 83.9; r2 = .91); 7) intra- and interassay coefficients of variation were 3.3 and 10.6%, respectively. The EIA developed in this project is a valid and reliable method for quantitating PGFM in extracts of bovine plasma. PMID- 1609120 TI - Generation of 5-lipoxygenase metabolites following pulmonary reperfusion in isolated rabbit lungs. AB - We characterized the release of arachidonic acid (AA) metabolites in lung effluent following lung ischemia-reperfusion since they may contribute to the pathophysiology of reperfusion lung injury. The left pulmonary artery of rabbits (N = 5) was occluded for 24 hrs with a surgically implanted vascular clip. At 24 hrs, the heart and lungs were removed en bloc and perfused with Ringers-albumin (0.5 gm%) at 60 ml/min while statically inflated with 95% O2-5% CO2. The lipid fraction of the lung effluent was concentrated using the Bligh-Dyer extraction and analyzed by gradient RP-HPLC. Samples obtained in the first minute of reperfusion showed significant increases in LTB4 (+180%), LTC4 (+3600%), 15-HETE (+370%), 5-HPETE (+270%), PGE2 (+140%), 6-keto-PGF1 alpha (+110%) and 12-HHT (+160%) compared to the effluent from the right control lung. The reperfusion induced increases in LTB4, LTC4, LTD4 and 15-HETE were inhibited greater than or equal to 70% by pretreatment with the 5-LO inhibitors L663,536 or L651,392. The increases in lipid concentrations corresponded to significantly increased pulmonary arterial pressure from a baseline value of 9.5 +/- 0.3 to 29.3 +/- 2.9 (cmH2O) during the first min of reperfusion. The pulmonary arterial pressure remained elevated for at least 20 min of reperfusion. Reperfusion also resulted in PMN uptake (assessed by lung tissue myeloperoxidase content) in the reperfused lung versus control lung (25.0 +/- 2.4 vs. 10.5 +/- 2.5 units). The generation of lipoxygenase metabolites during the initial phase of reperfusion may contribute to post-reperfusion PMN uptake and pulmonary vasoconstriction. PMID- 1609121 TI - Acute hypoxia alters eicosanoid production of perfused pulmonary artery endothelial cells in culture. AB - Hypoxia alters vascular tone which regulates regional blood flow in the pulmonary circulation. Endothelial derived eicosanoids alter vascular tone and blood flow and have been implicated as modulators of hypoxic pulmonary vasoconstriction. Eicosanoid production was measured in cultured bovine pulmonary endothelial cells during constant flow and pressure perfusion at two oxygen tensions (hypoxia: 4% O2, 5% CO2, 91% N2; normoxia: 21% O2, 5% CO2, 74% N2). Endothelial cells were grown to confluence on microcarrier beads. Cell cartridges (N = 8) containing 2 ml of microcarrier beads (congruent to 5 x 10(6) cells) were constantly perfused (3 ml/min) with Krebs' solutions (pH 7.4, T 37 degrees C) equilibrated with each gas mixture. After a ten minute equilibration period, lipids were extracted (C18 Sep Pak) from twenty minute aliquots of perfusate over three hours (nine aliquots per cartridge). Eicosanoids (6-keto PGF1 alpha; TXB2; and total leukotriene [LT - LTC4, LTD4, LTE4, LTF4]) were assayed by radioimmunoassay. Eicosanoid production did not vary over time. 6-keto PGF1 alpha production was increased during hypoxia (normoxia 291 +/- 27 vs hypoxia 395 +/- 35 ng/min/gm protein; p less than 0.01). Thromboxane production (normoxia 19 +/- 2 vs hypoxia 20 +/- 2 ng/min/gm protein) and total leukotriene production (normoxia 363 +/- 35 vs hypoxia 329 +/- 29 ng/min/gm protein) did not change with hypoxia. These data demonstrated that oxygen increased endothelial prostacyclin production but did not effect thromboxane or leukotriene production. PMID- 1609122 TI - Intracellular Ca2+ mobilization and not calcium influx promotes phorbol ester stimulated thromboxane A2 synthesis in human platelets. AB - Phorbol esters, potent activators of protein kinase C (PKC), greatly enhance the release of arachidonic acid and its metabolites (TXA2, HETES, HHT) by Ca2+ ionophores in human platelets. In this paper, we report the relationship between intracellular Ca2+ mobilization and external calcium influx into platelets and the ability of PMA plus A23187 to promote thromboxane A2 (TXA2) synthesis. The enhanced levels of TXA2 due to the synergistic stimulation of the platelets with A23187 and phorbol esters are not affected significantly by the presence of external Ca2+ or the calcium-chelator EGTA. PKC inhibitors, staurosporine and sphingosine, abolished phorbol myristate acetate (PMA) potentiation of TXA2 production which strongly supports the role of PKC in the synergism. Platelet aggregation is more sensitive to PMA and external calcium than TXA2 formation. PMA increased TXA2 production as much as 4-fold at low ionophore concentrations. The A23187-induced rise in [Ca2+]i was reduced by pretreatment of human platelets with phorbol esters, both in the presence and absence of EGTA, and staurosporine reversed this inhibitory effect. These results indicate that the synergistic stimulation of TXA2 production by A23187 and phorbol esters is promoted by intracellular Ca2+ mobilization and not by external calcium influx. Our data also suggest that PKC is involved in the regulation of Ca2+ mobilization from some specific intracellular stores and that PKC may also stimulate the Ca(2+) dependent phospholipase A2 at suboptimal Ca2+i concentrations. PMID- 1609123 TI - Variability of dose specifications in endoluminal brachytherapy. PMID- 1609124 TI - Dosimetry of intraluminal brachytherapy. AB - Dose specification in intraluminal brachytherapy varies considerably in the literature. A terminology is proposed, inspired from the Paris System of interstitial brachytherapy, to define some dosimetric guidelines. The dose is specified in the central plane which is a plane perpendicular to the source and passing through its centre. The reference dose rate is calculated in this plane. The treated volume is the volume encompassed by the reference isodose. The hyperdose sleeve is the volume receiving a dose equal to or greater than twice the reference dose. A study of the dose distribution along a linear source of iridium-192 was undertaken. Results obtained, also valid for caesium-137 and cobalt-60, show that the radius of the hyperdose sleeve is relatively independent of the length of the source. It is approximately 0.6 times the distance between the source axis and the point of dose specification when the active length varies from 3 to 20 cm. Reporting not only the dose, but also the thickness of tissue covered by the reference isodose and the thickness of tissue included in the hyperdose sleeve, is recommended to assist in evaluation of the results of treatment and to facilitate the exchange of clinical information in intraluminal brachytherapy. Practical examples are given. PMID- 1609125 TI - Human errors in data transfer during the preparation and delivery of radiation treatment affecting the final result: "garbage in, garbage out". AB - Due to the large number of steps and the number of persons involved in the preparation of a radiation treatment, the transfer of information from one step to the next is a very critical point. Errors due to inadequate transfer of information will be reflected in every next step and can seriously affect the final result of the treatment. We studied the frequency and the sources of the transfer errors. A total number of 464 new treatments has been checked over a period of 9 months (January to October 1990). Erroneous data transfer has been detected in 139/24,128 (less than 1%) of the transferred parameters; they affected 26% (119/464) of the checked treatments. Twenty-five of these deviations could have led to large geographical miss or important over- or underdosage (much more than 5%) of the organs in the irradiated volume, thus increasing the complications or decreasing the tumour control probability, if not corrected. Such major deviations, only occurring in 0.1% of the transferred parameters, affected 5% (25/464) of the new treatments. The sources of these large deviations were nearly always human mistakes, whereas a considerable number of the smaller deviations were, in fact, consciously taken decisions to deviate from the intended treatment. Nearly half of the major deviations were introduced during input of the data in the check-and-confirm system, demonstrating that a system aimed to prevent accidental errors, can lead to a considerable number of systematic errors if used as an uncontrolled set-up system. The results of this study show that human mistakes can seriously affect the outcome of patient treatments.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609126 TI - Iridium-192 brachytherapy in the management of 147 T2N0 oral tongue carcinomas treated with irradiation alone: comparison of two treatment techniques. AB - Our purpose is to analyse local control, complications relative to the proportion of total dose delivered by external beam irradiation versus interstitial implant in 147 patients with previously untreated T2N0 squamous cell carcinoma of the oral tongue, managed between 1973 and 1986 (UICC staging system). These T2N0 patients are part of a larger group of 430 patients with oral tongue carcinoma (T1, T2, T3) treated with irradiation alone. Of these 147 T2N0 patients, 70 were treated with interstitial implant alone and 77 with both external beam irradiation and implant. In the group treated with interstitial implant alone, the 5-year local control was 89.8% against 50.6% in those treated with external beam irradiation and interstitial implant (log-rank test, p = 0.00002); 67.6% versus 46.5% for locoregional control (p = 0.029); and 62.2% versus 34.7% for specific survival (p = 0.0015). Since 1980, all the patients treated by iridium implantation were protected with a leaded spacing device between the tongue and the mandible. Soft tissue necrosis and bone exposure following treatment were scored according to the following criteria: minor, moderate or severe. Seven moderate and one severe complications were recorded in the brachytherapy group. None of the patients required surgery. In the combined treatment group, six moderate and two severe complications were observed. Patients treated with interstitial implant alone, and showing moderate or severe complications had received an average brachytherapy dose of 7600 cGy. In the same group, the patients without complications had received an average dose of 6800 cGy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609127 TI - The prognostic value of hemoglobin and a decrease in hemoglobin during radiotherapy in laryngeal carcinoma. AB - An association between a low Hb-content and a poor response on radiation therapy has been established in previous years, especially in patients with squamous cell carcinomas. Whether this is linked with hypoxic conditions of the tumour or associated with tumour volume, blood loss or other conditions, is not yet known for certain. Patients with small head and neck tumours seem to form an interesting group to study this issue because several factors can be ruled out. Therefore, a retrospective analysis of 306 patients with glottic or supraglottic carcinoma was performed, to identify whether the Hb-value was of prognostic importance and whether this was linked to other patient characteristics. All patients were treated with primary radiotherapy with doses ranging from 60 to 70 Gy in 6-7 weeks. It appeared that in glottic carcinoma, the disease-free survival was significantly worse in patients with a Hb-value below normal at the start or/and at the end of therapy (p = 0.09, p = 0.0012, respectively). In patients with supraglottic carcinoma, the above mentioned difference approved only for a Hb-value below normal at the end of treatment (p = 0.05). A decrease in Hb-level of greater than or equal to 0.5 mmol/l during therapy, regardless whether the Hb values were within or beyond normal range, reduced the disease-free survival in patients with glottic carcinoma (p = 0.0125). In a multivariate analysis, the Hb value at the end of treatment proved to be an independent prognostic factor after T- and N-classification. There was no relationship with nutritional condition of the patient, nor with the Karnofsky Performance scale.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609128 TI - Results of post-operative or exclusive radiotherapy in grade I and grade II cerebellar astrocytoma patients. AB - 43 Patients with the diagnosis of cerebellar astrocytoma were post-operatively treated, between 1 January 1976 and 31 December 1985. Their age ranged between 2 and 51 years with a median of 13. There were 22 males and 21 females. The tumours were reported as grade I in 18, and grade II in 25 patients. The primary surgical intervention was in the form of biopsy in 3, subtotal excision in 24 and macroscopic total excision in 16. All patients were treated with cobalt-60 teletherapy unit, to a total tumour dose of 4500-5500 cGy in 6-7 weeks. The obtained 5 and 10 year actuarial survival rates are 78% and 78%. Our study gives the impression that, age, sex and tumour grade are not determining factors in survival and post-operative radiotherapy improves prognosis in cases treated by subtotal excision while it remains unnecessary in those who had undergone total surgical removal. PMID- 1609130 TI - Accuracy of patient positioning in mantle field irradiation. AB - A prospective study of the accuracy of patient positioning in mantle field irradiation was carried out in 13 lymphoma patients treated with curative radiotherapy. Patients were treated in the supine and prone position for anterior and posterior fields, respectively. Individually shaped divergent shielding blocks were placed in a fixed position in a template which was positioned on a tray above the patient. A total number of 94 megavoltage portal films (MV) was analysed and compared to 26 simulation films (SIM). MV-SIM differences were larger for posterior fields than for anterior fields. Regarding the position of the lung shielding blocks, mean MV-SIM differences ranged from 1.3 to 4.4 mm and errors exceeding 1 cm were found in 7.2% of cases. Most discrepancies appeared to be randomly distributed. A 4-5 mm systematic cranial shift of patients in the posterior treatment position was noted. Discrepancies in the position of the laryngeal block, spinal cord shielding block and humerus blocks were small with mean MV-SIM differences ranging from 0.3 to 2.7 mm. Differences between simulation set-up and treatment set-up were modest as compared to error rates reported in the literature. Shielding of tumour-bearing areas did not occur. It was concluded that the present standardised technique of patient positioning and the design of treatment fields results in acceptable error rates. Attention should be directed towards increasing the stability of patients in the prone treatment position in order to further reduce both systematic and random error rates. PMID- 1609129 TI - Reirradiation tolerance of the immature rat spinal cord. AB - The dose dependence and time course of long-term recovery in the cervical spinal cord of 3-week-old rats was investigated, and compared with the recovery in adults rats. At intervals of 1 to 168 days after initial irradiation of the cervical spinal cord at the age of 3 weeks, reirradiation experiments were performed to test the pattern of long-term recovery in immature spinal cord. The single dose ED50 for white matter mediated paresis was about 21 Gy for 3-week-old as well as adult rats, although the latency to paresis development increased from about 90 days in 3-week-old rats to about 250 days in adult rats. The main long term recovery was seen during the first month after the initial radiation treatment at 3 weeks. This is in contrast to long-term recovery in adult rats, in which the main recovery took place between 2 and 6 months after the first irradiation. Calculations according to the LQ model showed that the extra dose that can be given to the cervical spinal cord after a 1-6 months interval in the 3-week-old rats reaches a maximum of about 20% of the total biological effect resulting in paresis. In adult rats the extra dose that can be given to the cervical spinal cord after a 6 months interval represents about 40% of the total biological effect. These studies show that time course as well as extent of long term recovery from radiation treatment not only depends on tissue and species, but also on age. PMID- 1609132 TI - The never-ending controversy about TBI schedules. PMID- 1609131 TI - A simple technique for film dosimetry. AB - Dose distributions showing the effect of custom made compensators may be produced using measured data unique to the compensator. A fast method of obtaining this data with film is described. The problem of dose versus density response is avoided by an appropriate choice of the given dose to the film. PMID- 1609133 TI - Treatment time in bladder cancer. PMID- 1609134 TI - Overall treatment time in the radiotherapy of transitional cell cancer of the bladder. PMID- 1609135 TI - Evaluation of articular cartilage: radiographic and cross-sectional imaging techniques. AB - Many diagnostic modalities may be used to evaluate articular cartilage. Plain radiography remains the preferred initial study for cartilage evaluation, although even specialized views such as weight-bearing, tunnel, and flexion lateral projections are insensitive in the detection of early cartilage loss. Compared with newer modalities, conventional arthrography has limited capacity for the assessment of cartilage. Computed tomography performed after intraarticular injection of contrast material (ie, CT arthrography) has improved accuracy but is essentially limited to the axial plane. Magnetic resonance (MR) imaging, with its superb soft-tissue contrast and multiplanar capabilities, has shown promise in depicting articular cartilage. Cartilage is best depicted when an "arthrogram effect" is present, achieved with T2-weighted spin-echo imaging, with some gradient-echo pulse sequences, and when intraarticular contrast material is used. If performed with such techniques, MR imaging is the method of choice for evaluating specific cartilage loss, osteochondritis dissecans, and other osteochondral abnormalities. PMID- 1609136 TI - Normal anatomy and pathologic conditions of ankle tendons: current imaging techniques. AB - Radiologic assessment of tendon injuries requires familiarity with normal anatomy and the capabilities of available imaging modalities. Tenography, less commonly used nowadays, does not allow direct visualization of tendons, so that partial ruptures and longitudinal splits may go undetected. Ultrasonography can depict tenosynovitis, tendinitis, and complete tendon rupture of the Achilles tendon, but the other tendons are difficult to visualize with this technique. Magnetic resonance (MR) imaging is superior to computed tomography (CT) in the depiction of tenosynovitis and peritendinitis, tendinitis, tendon rupture, and tendon dislocation and subluxation. CT can demonstrate these abnormalities, but accompanying scar tissue or edema, early changes of tendon degeneration, and small amounts of inflammatory fluid are difficult to differentiate with this technique. CT is superior for demonstrating calcifications, convex retromalleolar groove, bone fragments, or spurs that complicate tendon dislocation and rupture. Although the authors prefer MR imaging, they caution that all of the modalities are not always specific and that differentiation between closely related processes such as tendinitis and early tendon rupture is difficult. PMID- 1609138 TI - Sticker shock in health care: do you really know what things cost? PMID- 1609137 TI - MR imaging of the female pelvic region. AB - Magnetic resonance (MR) imaging is a valuable technique for noninvasive evaluation of the female pelvic region. This article presents the normal anatomy and abnormalities of the female pelvis. MR imaging may be more useful than clinical evaluation or other imaging modalities in diagnosing or staging developmental anomalies, leiomyomas, adenomyosis, endometrial or cervical carcinoma, vaginal neoplasms, ovarian cysts, endometriosis, teratomas, polycystic ovaries, or other ovarian masses. It could potentially replace laparoscopy as a more useful tool in the diagnosis of uterine anomalies. MR imaging is generally capable of helping determine whether a pelvic mass is uterine or adnexal in origin and may be used to characterize some adnexal masses. In some cases, MR imaging is used to differentiate recurrent disease from posttreatment fibrosis, which aids in treatment planning. PMID- 1609140 TI - CT and MR imaging of the pediatric orbit. AB - Orbital abnormalities encountered in the pediatric population differ substantially from those found in adult patients. Retinoblastoma, the most serious intraocular tumor, is often difficult to diagnose, but use of computed tomography (CT) (which reveals the characteristic focal calcification) and magnetic resonance (MR) imaging allows this tumor to be differentiated from pseudogliomas, such as Coats disease, and retrolental fibroplasia. CT and MR imaging help in the differentiation of orbital cellulitis from preseptal, lacrimal, and eyelid infectious processes and of orbital pseudotumor from Graves disease. In cases of orbital trauma, CT is excellent for detecting orbital fractures and metallic foreign bodies; MR imaging is better for depicting ocular and optic nerve injuries. Both modalities allow the differentiation of rhabdomyosarcoma from dermoid, cavernous hemangioma, and lymphangioma and provide helpful information for the diagnosis of many other tumors. Since CT and MR imaging have widely expanded the capabilities of orbital imaging, it is more important than ever before for radiologists to understand pediatric orbital disease. PMID- 1609139 TI - Pediatric pelvis: radiographic appearance in various congenital disorders. AB - This article presents the spectrum of pelvic abnormalities in developmental diseases of bone. The pelvis comprises the ilium, ischium and pubis, and the sacrum. Knowledge of pelvic embryology and normal development is essential in recognizing pelvic abnormalities and disorders, which involve the number of bone elements, rate of ossification, density, and size or shape. Anarchic development of bone and dysplasias identifiable at birth must also be considered. The pelvis is important in the evaluation of such disorders because of the frequent, varied, and often specific radiologic abnormalities. The pelvis may also be the first evidence for a congenital malformation syndrome because it is often included in routine radiographic examinations. PMID- 1609141 TI - CT of focal pulmonary masses in childhood. AB - Focal pulmonary masses in children encompass a spectrum of conditions including congenital lesions, inflammatory masses, hematomas, and benign and malignant tumors. Congenital masses include bronchial atresia, sequestration, cystic adenomatoid malformation, and pulmonary vascular anomalies. Inflammatory masses most commonly result from infection and include pulmonary abscess, granulomas, and postinflammatory pseudotumors. Blunt trauma can cause a hematoma, which decreases in size on serial radiographs. Pulmonary neoplasms may be benign such as papilloma, hamartoma, and bronchial carcinoid tumor (low-grade malignancy), or they may be malignant as in sarcoma, carcinoma, and pulmonary blastoma. Because computed tomography (CT) is the most sensitive technique in detecting and helping characterize parenchymal disease, it has become the procedure of choice for further investigation of lesions seen or suggested on plain chest radiographs. Understanding the CT appearance of these lesions can allow an accurate diagnosis and optimize management of the patient's condition. PMID- 1609142 TI - Imaging of pulmonary histiocytosis X. AB - Pulmonary histiocytosis X is an uncommon but important cause of pulmonary fibrosis and honeycombing in young adults. This article reviews the pathologic, clinical, radiographic, and high-resolution computed tomographic (HRCT) features of pulmonary histiocytosis X, focusing on differential diagnosis and disease progression. The main pathologic feature of pulmonary histiocytosis X is peribronchiolar inflammation, leading to fibrosis and cyst formation. Although the diagnosis of pulmonary histiocytosis X may be suspected on the basis of chest radiographic findings, the HRCT findings of predominantly upper lobe nodules and cysts are virtually pathognomonic of this disorder. As pulmonary histiocytosis X progresses, the nodules decrease in number, leaving multiple thin-walled cysts. HRCT can be useful in visually estimating the proportion of lung involved and is also valuable in distinguishing histiocytosis from other disorders that produce nodules or cysts. Chest HRCT helps confirm the pattern seen at radiography and is valuable in establishing the correct diagnosis. PMID- 1609143 TI - Normal venous anatomy and collateral pathways in upper extremity venous thrombosis. AB - Collateral pathways are well known in superior vena cava occlusion but not in axillary or subclavian vein occlusion, even though these occlusions are becoming more common. In a series of 127 arm venograms obtained for suspected venous thrombosis, the authors found 32 instances of subclavian or axillary vein occlusion. The authors reviewed the cases for site of occlusion and definition of collateral pathways. In 15 cases, the occlusion was in the subclavian vein, with collateral flow established chiefly via veins in the neck. Ten cases of axillary vein occlusion with chest wall collateral pathways were identified. Seven cases could not be categorized. Knowledge of these pathways is useful for accurate interpretation of upper extremity venograms. A more thorough understanding of venous pathways in the upper body may aid in the treatment of patients with chronic disease and longterm indwelling central venous catheters. PMID- 1609144 TI - PACS mini refresher course. Network and ACR-NEMA protocols. AB - The backbone of the picture archiving and communication system (PACS) is the electronic network used to move information. Communications networks require electronic rules of operation or protocols so that a set of data being transmitted reaches the intended destination and does not collide with another set of transmitted data. The most efficient protocol is flexible and can respond to the fluctuations in volume of data transmitted via the network. Successful network connection of PACS devices requires standardized interfaces so that equipment from multiple vendors can use the network protocol. The American College of Radiology (ACR) and the National Electrical Manufacturers Association (NEMA) have developed a standard for imaging equipment interfaces: DICOM (Digital Imaging and Communications in Medicine). The DICOM standard allows interoperability among different computers and operating systems. It is flexible and will allow modification and expansions as new imaging techniques evolve. The authors and the ACR-NEMA committee believe that the DICOM standard represents an important choice for radiologists, since it was developed with their interests in mind. PMID- 1609145 TI - PACS mini refresher course. Local area network topologies, media, and routing. AB - Picture archiving and communication systems (PACS) use local area networks (LANs) for the transfer of images and image-related data. There are several aspects of LANs that are used to describe and categorize them: topology, the media used for transmission, and the medium access control (MAC) protocols. The four basic topologies are the bus, tree, ring, and star; the four primary types of media used for LANs include coaxial cable, twisted-pair wire, fiberoptic cables, and wireless. The wireless LANs that use infrared and radio frequencies are new but promising. Of the three MACs presently being used--Ethernet, fiber distributed data interface (FDDI), and UltraNet--Ethernet is the most common. LANs can be interconnected by means of the repeater, bridge, router, and gateway internetworking devices. The future of LAN development lies in increased standardization and increased connectivity in order to make teleradiology a reality. PMID- 1609146 TI - PACS mini refresher course. Wide area network strategies for teleradiology systems. AB - Teleradiology systems require the use of wide area networks (WANs). Design and implementation of a WAN depend on the number of images to be transmitted, desired digital image throughput (based on signaling rate), and cost of the communications link. Image transmission load must be estimated before the communications link can be selected. Communications links used in WANs include T 1 carrier point-to-point service, digital service (DS)-1 dial-up service, DS-3 point-to-point service, DS-0 dial-up service, digital microwave, fiberoptic local loop carriers, and metropolitan area networks (MANs). Depending on the distance between sites, T-1 service may be less costly than DS-1 service; however, for distances more than 200 miles, DS-1 service can be less expensive and more flexible. Both of these services and DS-0 service have lower signaling rates than DS-3 service, which is the fastest and most expensive link. Microwave and fiberoptic links are less expensive but have distance limitations of 14 and 30 miles, respectively. MANs are still being developed but hold the promise of higher signaling rates at lower costs. PMID- 1609147 TI - Pineal region masses: differential diagnosis. AB - Most pineal region masses are malignant germ cell neoplasms that occur in young male patients. The most common is a germinoma, which is a homogeneous mass with signal intensity and attenuation similar to those of gray matter; the mass engulfs a densely calcified pineal gland. Teratomas are multilocular heterogeneous masses containing lipid areas. Other types of pineal region masses include choriocarcinoma, endodermal sinus tumor, and embryonal carcinoma. Pineal parenchymal neoplasms are usually either pineocytomas or pineoblastomas, which may "explode" preexisting pineal calcifications. Unlike the germinomas, they have no sexual predilection and may be seen in patients who are 20 years of age or older. Although the correct histologic diagnosis may be suggested with a careful evaluation of the morphologic features, attenuation, and signal intensity characteristics, very few of these tumors have a truly pathognomonic imaging pattern. Thus, histologic verification is necessary for most pineal region masses that appear to be neoplastic. PMID- 1609148 TI - Ultrasound case of the day. Endometrial implant arising in the cesarean scar. PMID- 1609149 TI - General case of the day. Secondary involvement of the breast with a non-Hodgkin lymphoma, B-cell type. PMID- 1609150 TI - Pediatric case of the day. Acute iron ingestion. PMID- 1609151 TI - Why (continue to) study physics? PMID- 1609152 TI - Controversies and uncertainties concerning the pathologic features and pathologic diagnosis of asbestosis. AB - Asbestos is a fibrous silicate mineral that has been known for decades to cause pulmonary scarring, referred to as asbestosis. The simplest definition of asbestosis is the presence of pulmonary fibrosis as a result of accumulation of airborne asbestos in the lungs. Not infrequently, the terms "asbestos" and "asbestosis" are used incorrectly (interchangeably) by medical personnel, and sometimes pleural fibrosis caused by asbestos is incorrectly referred to as asbestosis. The earliest lesion of asbestosis, as defined by the CAP-NIOSH Committee is peribronchiolar fibrosis, although controversy exists as to how specific this lesion is with respect to causation by asbestos, and whether this lesion progresses to grade 4 asbestosis. In addition, some authorities in the field suggest that the term "asbestosis" be used only for diffuse interstitial fibrosis. The mechanism by which asbestos causes interstitial fibrosis remains poorly understood, and in recent years, pathologic changes such as organizing pneumonitis-bronchiolitis obliterans, and lymphocytic interstitial pneumonitis, have been described in persons occupationally exposed to asbestos, suggesting that the pulmonary lesions caused by asbestos represent a wider spectrum than had previously been appreciated. By defining areas of uncertainty, medical science will eventually clarify areas of disagreement concerning asbestosis which will eventually lead to a better understanding of this disease. PMID- 1609153 TI - Asbestos and the histogenesis of lung carcinoma. AB - Individuals exposed to asbestos develop and die of bronchogenic carcinoma at rates well above individuals not exposed, but there is disagreement as to what factors other than the asbestos may be important in the histogenesis of the carcinoma. This report discusses the various theories as to how and why asbestos, cigarette smoke, asbestosis, and pleural disease may be involved in the development of the carcinoma. The authors conclude that other disease processes may mark individuals particularly likely to develop carcinoma of the lung, but that asbestos fibers have an independent role in the histogenesis of carcinoma of the lung. PMID- 1609154 TI - Pseudomesotheliomatous adenocarcinoma: a reappraisal. AB - Adenocarcinomas of or in lung that clinically and pathologically mimic diffuse pleural mesotheliomas are rare. We reviewed selected clinical and pathologic features of 15 autopsy/surgical cases previously reported in the medical literature and of 15 additional cases from the files of the Armed Forces Institute of Pathology (AFIP). Ninety percent of the patients were men. The median age was 61 years. Sixty-three percent of the patients smoked, 17% of them had possible or definite occupational exposure to asbestos, and one patient had microscopically proven asbestosis. Most patients had chest pain, shortness of breath, or cough, and had unilateral pleural effusion in the chest x-ray. At thoracotomy or at autopsy, numerous nodules, plaques, or a continuous rind of tumor was present over the pleural surface. Microscopically, the tumors showed simplified glands, nests, cords, papillary, tubulopapillary or biphasic patterns of growth. The neoplasms contained mucin that stained with diastase-predigested periodic acid-Schiff (PAS), mucicarmine, and alcian blue (with or without hyaluronidase predigestion). All patients died with/of tumor, with a mean survival of 4.7 months for those reported in the medical literature and of 7 months for those in the AFIP files. These adenocarcinomas therefore mimic pleural mesothelioma not only in their clinical and gross and microscopic appearance, but also in their prognosis. PMID- 1609155 TI - Differential diagnosis between mesothelioma and adenocarcinoma: a multimodal approach based on ultrastructure and immunocytochemistry. AB - Most compensations for asbestos-related deaths secondary to cancer center around mesothelioma and bronchogenic carcinoma. The differential diagnosis between mesothelioma and adenocarcinoma is a common and troublesome one, necessitating the correlation between clinical history, radiographic findings, and pathologic examination of tissues and cells. We describe a multimodal approach based on the use of routine and special stains, immunocytochemistry, and electron microscopy for distinguishing between mesothelioma and adenocarcinoma. Once a malignant diagnosis is arrived at by careful pathological examination, the tumor is classified as mesothelioma if mesothelial cells are identified as the constituent cells of the neoplasm. Mesothelial cells are recognized by (1) their main ultrastructural features: slender and elongated microvilli, abundant intermediate filaments, and lacking secretory granules; and (2) their characteristic immunocytochemical reactivity: positivity for cytokeratin, EMA, and vimentin, and negativity for carcinoembryonic antigen (CEA), B72-3, Leu-M1, and other gland cell markers. A variety of methods have been attempted in an effort to distinguish between reactive and malignant mesothelial cells. In practice, however, such distinction depends more on experience and expertise than in any fool-proof ancillary tests. A number of these tests are discussed along with the illustration of classical and unusual examples of mesothelioma and other pleural tumors. PMID- 1609156 TI - Malignant mesothelioma: cytologic diagnosis with histologic, immunohistochemical, and ultrastructural correlation. AB - The differential diagnoses of malignant mesothelioma in serous effusions include adenocarcinoma and reactive mesothelial cells. While several cytologic features are of predictive value in separating these entities, immunostaining and ultrastructural examination are important adjuncts that increase the diagnostic yield. Many of the cytomorphologic features can be correlated with immunohistochemical and ultrastructural findings. Most important among these is the ultrastructural demonstration of long, often branching microvillous processes in malignant mesothelial cells. Corresponding microvilli can be visualized by immunostaining for epithelial membrane antigen in both cell block preparations from effusions and biopsy specimens, allowing the identification of malignant mesothelioma. In addition, the circumferential distribution of these immunostained microvilli in cells dispersed in stromal connective tissue identifies them as malignant mesothelial cells, corresponding to the ultrastructural appearance of aberrant microvilli, which project through deficiencies in the basal lamina. These microvilli show interdigitation with stromal collagen fibers, a phenomena not observed in adenocarcinoma. PMID- 1609157 TI - The concept of mesothelioma in situ: implications for diagnosis and histogenesis. AB - The concept of mesothelioma in situ is explored by a detailed examination of seven patients, subsequently proven to have pleural malignant mesothelioma, who initially had no evidence of gross tumor and for whom biopsy material was available at this early presentation. The tissue was assessed by routine microscopy, the immunoperoxidase technique for epithelial membrane antigen and silver staining for nucleolar organizer regions. Tiny lesions of the pleura that merged with or were adjacent to microscopically flat monolayered or folded mesothelium with cytological atypia were observed. The atypical cells reacted positively to epithelial membrane antigen, and the nucleolar organizer region counts were elevated. These observations are considered to support the possibility of the presence of mesothelioma in situ. These findings are discussed in the light of the proposed concept of mesothelioma in situ, its histogenesis, and its possible clinical relevance. PMID- 1609158 TI - Quantitative and analytical studies in the diagnosis of mesothelioma. AB - The vast majority of patients with malignant mesothelioma of the pleura or peritoneum have an abnormal tissue asbestos content as assessed by digestion techniques. These procedures allow for the quantification of asbestos bodies, as well as numbers and types of mineral fibers. In general, analyses of mineral fiber content correlate well with occupational exposure history. Such analyses are useful for the identification of asbestos-related mesotheliomas and separation from those due to other causes. PMID- 1609160 TI - Asbestos-related diseases: diagnostic challenges and medicolegal implications. PMID- 1609159 TI - The spectrum of histologic growth patterns in benign and malignant fibrous tumors of the pleura. AB - A review of the histologic growth patterns in 50 cases of benign and malignant fibrous tumors of the pleura (localized or solitary fibrous tumor, fibrous mesothelioma) is presented. Two major histologic growth patterns were observed admixed in various proportions: solid spindle and diffuse sclerosing. The solid spindle growth pattern assumed various configurations, including fascicular areas, storiform and herringbone formations, angiofibroma and hemangiopericytoma like areas, synovial sarcoma-like areas, and neural-type palisading, thus simulating a variety of soft-tissue neoplasms. The diffuse sclerosing pattern, although rarely assuming a dominant role, was present in varying proportions in virtually all cases. In areas with extensive sclerosis, focal degeneration of collagen simulating tumor necrosis was often present. Other less frequently observed features were the formation of "amianthoid" fibers, multinucleated giant cells, and foci of metaplastic ossification. On ultrastructural and immunohistochemical examination, the tumor cells showed nondistinct features. Due to the extreme variability in morphologic appearances and the lack of distinctive ultrastructural or immunohistochemical characteristics, these tumors can pose a significant diagnostic problem. Familiarity with their histologic appearances and correlation with the gross findings and clinical setting are essential for arriving at the correct diagnosis. PMID- 1609161 TI - Asbestos-related diseases: a historical and mineralogic perspective. PMID- 1609162 TI - Clinical controversies in asbestos-induced lung diseases. AB - Asbestos is a heterogeneous mineral fiber with considerable heat resistance and sound-abatement properties. It is relatively easily mined and processed and has been applied in a number of forms to ships and buildings. Unfortunately, respirable asbestos fibers have significant pathologic effects on the human lung and other organs. These effects can result in characteristic pleuropulmonary diseases, which become manifest after a latency period of 10 to 40 years from first exposure. This brief review will outline some major current controversies in the clinical approach to evaluation of asbestos-induced lung diseases. PMID- 1609163 TI - Pandemic influenza: a zoonosis? AB - In the last two decades, influenza A viruses have been found to occur throughout the animal kingdom, mainly in birds, notably aquatic ones, in which infection is largely intestinal, waterborne, and asymptomatic. The domestic duck of southern China, raised in countless numbers all year round mainly as an adjunct to rice farming, is the principal host of influenza A viruses. Studies based on Hong Kong H3N2 viruses from southern China suggest that pandemic strains originate from the domestic duck there and are transmitted to humans via the domestic pig, which acts as a "mixing vessel" for two-way transmission of viruses. This provides further support for the hypothesis that the region is a hypothetical influenza epicenter. Rural dwellers in the epicenter show serological evidence of contact with non-human influenza A viruses. Two hypotheses are advanced for the range of hemagglutinin (HA) subtypes of viruses that can cause pandemics (1) circle or cycle limited to H1, H2, and H3 subtypes, thereby implying that a virus of the H2 subtype will cause the next pandemic; and (2) spiral, by which any one of the 14 HA subtypes recorded to date may be involved. Consideration is given to the temporal and geographical factors and range of hosts, namely the duck, pig, and human, that need to be submitted to virus surveillance in China and beyond to attempt to anticipate a future pandemic. Evidence is presented that points strongly to pandemic influenza being a zoonosis. PMID- 1609164 TI - Unique features of influenza viruses, and their implications. AB - Despite 50 years in intense research, influenza remains unique as the only truly pandemic viral infection of humans. In addition, although vaccines against this disease have been developed and used for the past four decades, they remain less effective than those used against other viral infections. Many of the reasons for this are now known, and depend on our understanding of the unique events that occur during virus replication. In particular, our understanding of virus variation following single infection, and the emergence of reassortant virus following double infection of cells, offers an explanation for many of the features of epidemic infection and forms a starting point for future scientific enquiry. Features of virus replication are discussed in this review, and the implications for the nature of epidemic infection and vaccine development are discussed. PMID- 1609165 TI - Clinical features of influenza. AB - Influenza, an acute, usually self-limited, febrile illness of global importance, appears virtually every year and infects the respiratory tract either sporadically, as a local outbreak, or as a widespread epidemic. The most severe outbreak known, the 1918 to 1919 influenza A pandemic, was responsible for an estimated 20 million deaths globally. In the United States, the influenza pandemics of 1957 and 1968 were associated with an attack rate of up to 50% and an estimated 100,000 deaths. Interpandemic influenza is responsible for considerable morbidity and mortality, which exceed that associated with the introduction of the pandemic strain. Influenza B infections resemble those due to influenza A, but are associated with fewer deaths. Features of influenza include headache, myalgia, malaise, anorexia, sore throat, nonproductive cough, sneezing, and nasal discharge; these symptoms are not pathognomic for influenza, and asymptomatic infection can occur. The pulmonary complications of influenza include pneumonia (viral and bacterial), croup, asthma, and bronchitis. Myocarditis and pericarditis are occasional cardiac complications. In addition to Reye's syndrome, a range of neurologic complications have been noted, including confusion, convulsions, psychosis, neuritis, Guillain-Barre syndrome, coma, transverse myelitis, and encephalomyelitis. Influenza has also been associated with the toxic shock syndrome, myositis, myoglobinuria, and renal failure. In view of its enormous human and economic toll, influenza remains a major target for improved vaccines and vaccine delivery, and antiviral treatment and prophylaxis. PMID- 1609167 TI - The diagnosis of influenza. AB - Our ability to establish a specific diagnosis of influenza infections has dramatically improved. Clinical signs and symptoms of influenza infection and epidemiological indicators of an influenza outbreak can be verified with a variety of rapid detection methods. Viral isolation and an acute change in serology, which characteristically took from 5 to 28 days, are now being supplemented with methods that detect influenza viral antigen directly on clinical specimens and/or influenza virus in tissue culture within 24 to 48 hours following inoculation. These rapid diagnostic techniques are easily adapted in clinical microbiology laboratories and will provide diagnostic information so that the clinician can prescribe specific antiviral therapy. PMID- 1609166 TI - Influenza: pathogenesis and host defense. AB - Our understanding of the host defense and pathogenesis of influenza has come from parallel studies in animal models and humans. Infection is initiated by deposition of influenza particles on either the upper respiratory tract epithelium or directly into the alveoli, with the former method having a lethal dose several orders of magnitude greater than the latter. The virus attaches to its cellular receptor by its hemagglutinin (HA); if this step is blocked by specific antibody, infection does not take place. The major role of antibody is in the prevention of disease. Even though serum antibody (primarily antihemagglutinin, but also antineuraminidase) has been known for decades to prevent viral pneumonia, it has only more recently been shown that passive administration of anti-influenza serum to virgin mice prevents pneumonia, but not rhinotracheitis. Further, intravenously administered anti-influenza IgA has been shown to be specifically transported into the nasal secretions and protect the murine nasopharynx against influenza infection. Whereas antibody is clearly required for protection against influenza, cytotoxic T-lymphocyte (CTL) activity is both necessary and sufficient for recovery from influenza. This was best shown in studies using nude (athymic) mice. Influenza-infected nude mice shed virus from their lungs indefinitely. Adoptive transfer of anti-influenza CTLs to influenza-infected nude mice will clear the virus from their lungs, whereas administration of anti-influenza antibody will lead to a cessation of viral shedding only as long as antibody is present. Influenza in aging presents a serious clinical problem. Recent studies suggest that the age-related decrease in anti-influenza CTL activity causes both prolonged viral shedding and increased viral spread through the respiratory tract. PMID- 1609168 TI - Influenza virus vaccine: a need for emphasis. AB - Each year, there are more than 20,000 influenza associated deaths during influenza virus epidemics. There is an increase in hospital admission for patients with pneumonia, exacerbation of chronic obstructive pulmonary disease, croup, and congestive heart failure, and an increase in school and industrial absenteeism. Yet only 30% of the high-risk target population receives influenza vaccination annually. Health care providers and patients are reluctant to use vaccine despite its generally excellent record of safety and its approximately 70% efficacy when vaccine and epidemic strains match. The continuing change in antigenic composition of the influenza A virus and waning immunity requires annual vaccination. Vaccine composition and target groups are reviewed. Strategies for improving vaccine usage are emphasized. PMID- 1609169 TI - Antivirals for the chemoprophylaxis and treatment of influenza. AB - Influenza virus infections are one of the leading causes of morbidity and mortality in the United States. Several antiviral agents, amantadine, rimantadine, and ribavirin, have been shown to be either therapeutically or prophylactically effective in influenza virus infections. Amantadine and rimantadine are effective, via the oral route, in treating and preventing influenza A infections. Aerosolized preparations of amantadine and rimantadine have also shown therapeutic efficacy against influenza A. Oral ribavirin has slight therapeutic efficacy in influenza A, but has also shown promising results in therapy of influenza B infections. Aerosolized ribavirin has also shown promise in treatment of patients who are severely ill with influenza A and B. PMID- 1609170 TI - Preventing influenza: the physician's role. AB - Influenza remains a preventable cause of illness and death in this country. Vaccination is the most cost-effective method for preventing influenza, and yet vaccination rates continue to be less than 30% to 40% for targeted high-risk groups. Physicians are in a unique position to provide the leadership and impetus needed to improve influenza vaccination rates for targeted groups. Contributors to physicians' success will include adequate knowledge of influenza and the vaccine, objective measures of current performance, and the ability to develop and implement successful immunization programs. It is likely that administrative and organizational changes in clinical practice will provide the critical elements for success. PMID- 1609171 TI - Predicting the prevalence of a disease in a cohort at risk. AB - A non-homogeneous Markov chain model is used to describe the evolution of a progressive chronic disease. Transition probabilities are estimated from data on coronary heart disease in Australia. By varying the transition probabilities, the effects of changes in medical management or in the natural history of the disease are examined. For reducing rates of fatal and non-fatal acute myocardial infarction a multifaceted strategy of primary and secondary prevention and improved acute care is found most effective. Primary prevention reducing the risk of early stages of the disease has the potential to yield the highest proportion of disease-free people. By contrast, intensive medical treatment of acute disease would reduce mortality but increase the total burden of disease in the population. PMID- 1609172 TI - Cluster randomization in large public health trials: the importance of antecedent data. AB - Large-scale public health trials are often randomized by geographic or administrative clusters, for reasons of financial or organizational exigency. In this paper, we deal with the situation where the dependent variable is a count of events, such as mortality from, or incidence of a given disease. Simulation results show that this design may decrease power by more than 50 per cent. The lost power can largely be replaced by incorporating information on the dependent variable, within clusters, before the start of the trial. The pretrial and trial data can be analysed by negative trinomial models. PMID- 1609173 TI - How many raters? Toward the most reliable diagnostic consensus. AB - When faced with a decision whether or not to treat a patient, to enter or to withdraw a patient from a clinical trial, or any other such binary decision, based on diagnosis with unsatisfactory reliability, can a consensus diagnosis be used to improve reliability? If so, exactly how? That is the question I address here. I draw comparisons and contrasts between the known results with an interval consensus and those with a binary consensus and suggest tactics for use in a pilot study to answer the above questions. PMID- 1609174 TI - Which measures of skewness and kurtosis are best? AB - Indices of distributional shape based on linear combinations of order statistics have recently been described by Hosking. Their usefulness as tools for practical data analysis is examined. They are found to have several advantages over the conventional indices of skewness and kurtosis (square root of b1 and b2) and no serious drawbacks. It is proposed, therefore, that they should replace square root of b1 and b2 in routine data analysis. To implement this suggestion, action by the developers of standard statistical software is needed. PMID- 1609175 TI - Directory of registries of clinical trials. AB - Registries of clinical trials are a potentially useful resource for the planning of new studies, the promotion of communication and collaboration between researchers, the conduct of meta-analyses, and the facilitation of patient access and recruitment to trials. However, many physicians and researchers are unaware of their existence, and as a result they remain underused. A directory of registries of clinical trials has been developed as a result of an international survey of 63 organizations and 51 individuals in 13 different countries to identify the existence of such registries. This is intended as a resource to keep physicians, researchers, trial organizers, funding bodies and government agencies abreast of the growing number of registries available, and to assist in the planning of future registries. Twenty-four current and six planned registries of clinical trials have been identified. Most focus on AIDS or oncology, but such diverse areas as neurosurgery, cardiovascular disease, dentistry and perinatology are also represented. This paper presents a descriptive profile on each registry and discusses the relative merits of their different organizational features. Recommendations are given for the establishment of future registries. PMID- 1609176 TI - Directory of registries of clinical trials. PMID- 1609177 TI - The use of subjective rankings in clinical trials with an application to cardiovascular disease. AB - Evaluating a clinical trial can be problematic if the studied treatments affect patients in many ways. A possible method for evaluating treatments is to have raters rank all the patients' trial experiences and then test whether the distribution of ranks differ between treatments. Before one can advocate such a procedure, however, one would like to be assured that raters agree fairly well with one another. As a first step in examining whether raters tend to agree, we conducted a small study with 20 raters evaluating 43 trial experiences from an imaginary cardiovascular clinical trial. Raters showed a high degree of consensus. Moreover, the average ranks agreed fairly well with two quantitative ranking rules. On the other hand, the average ranks did not agree very well with weightings usually selected in cardiovascular trials. These results suggest ranking may be a feasible approach to analysing certain clinical trials with multiple outcomes. PMID- 1609178 TI - Graphical representation of survival curves associated with a binary non reversible time dependent covariate. AB - The use of time dependent covariates has allowed for incorporation into analysis of survival data intervening events that are binary and non-reversible (for example, heart transplant, initial response to chemotherapy). We can represent this type of intervening event as a three-state stochastic process with a starting state (S), an intervening state (I), and an absorbing state (D), which usually represents death. In this paper we present three procedures for calculating survivorship functions which attempt to display the prognostic significance of the time dependent covariate. The first method compares survival from baseline for the two possible paths through the stochastic process; the second method compares overall survival to survival with state I removed from the process; and, the third method compares survival for those already in state I at a landmark time x to those in state S at time x who will never enter state I. We develop discrete hazard estimates for the survival curves associated with the three methods. Two examples illustrate how these methods can yield different results and in which situations one might employ each of the three methods. Extensions to applications with reversible binary time dependent covariates and models with both baseline and time dependent covariates are suggested. PMID- 1609180 TI - On the use of the generalized t and generalized rank-sum statistics in medical research. AB - We have used Monte Carlo methods to compare the type I error properties of the conditional and unconditional versions of the generalized t and the generalized rank-sum tests to those of the independent samples t and Wilcoxon rank-sum tests. Results showed inflated type I errors for the conditional generalized tests but not for the unconditional tests. We also compared the power of the unconditional generalized tests to that of the t and Wilcoxon tests under a variety of conditions. Results showed the generalized tests to be much more efficient than their traditional counterparts in some circumstances, but substantially less powerful in others. Based on these and other considerations, we conclude that the application of these newer statistics in medical research needs further consideration. PMID- 1609179 TI - Cross-validation performance of mortality prediction models. AB - Mortality prediction models hold substantial promise as tools for patient management, quality assessment, and, perhaps, health care resource allocation planning. Yet relatively little is known about the predictive validity of these models. We report here a comparison of the cross-validation performance of seven statistical models of patient mortality: (1) ordinary-least-squares (OLS) regression predicting 0/1 death status six months after admission; (2) logistic regression; (3) Cox regression; (4-6) three unit-weight models derived from the logistic regression, and (7) a recursive partitioning classification technique (CART). We calculated the following performance statistics for each model in both a learning and test sample of patients, all of whom were drawn from a nationally representative sample of 2558 Medicare patients with acute myocardial infarction: overall accuracy in predicting six-month mortality, sensitivity and specificity rates, positive and negative predictive values, and per cent improvement in accuracy rates and error rates over model-free predictions (i.e., predictions that make no use of available independent variables). We developed ROC curves based on logistic regression, the best unit-weight model, the single best predictor variable, and a series of CART models generated by varying the misclassification cost specifications. In our sample, the models reduced model free error rates at the patient level by 8-22 per cent in the test sample. We found that the performance of the logistic regression models was marginally superior to that of other models. The areas under the ROC curves for the best models ranged from 0.61 to 0.63. Overall predictive accuracy for the best models may be adequate to support activities such as quality assessment that involve aggregating over large groups of patients, but the extent to which these models may be appropriately applied to patient-level resource allocation planning is less clear. PMID- 1609181 TI - Strengthening some common multiple test procedures for discrete data. AB - This paper proposes modification of some commonly used multiple test procedures for testing problems that arise when the underlying distributions are discrete. These procedures have been shown as conservative because the exact nominal levels are unattainable. The amended procedures can achieve actual type I errors much closer to the nominal levels, thus giving rise to more powerful tests. PMID- 1609182 TI - Using an autoregressive model to detect departures from steady states in unequally spaced tumour biomarker data. AB - A new method, based on a continuous time autoregressive [CAR(1)] model of time series data, is provided for detecting departures of tumour markers from steady states in breast cancer patients following surgery. A Kalman filter recursive algorithm is used to calculate the likelihood function arising from the CAR(1) model and to calculate recursive residuals, which are monitored by a Shewhart Cusum scheme. This approach can be used to monitor the serial marker data of large numbers of patients even when the series are short and the data are serially correlated and unequally spaced. Further, the methodology can be used to recommend appropriate testing intervals. PMID- 1609183 TI - Maximum likelihood estimation of between and within variations in energy and protein intakes from infancy to adolescence for the Philippines. AB - The assessment of subjects' 'usual' intake of nutrients is important in assessing relationships between diet and disease and in identifying malnourished sub-groups of the populations. Estimation of the variation in intakes within subjects over time ('within variation') has importance in epidemiologic research; estimation of the between subject variation in the sample has use in defining the recommended dietary allowances that take into account the inter-individual differences. This paper estimates the between and within variances in the energy and protein intakes of 1189 Filipino children, based on 4 rounds of 24-hour recall data within a dynamic framework by means of maximum likelihood. The main findings are that the proportion of variation due to the within variance is higher for children from poorer households. Also, from the estimates of dynamic regression models for nutrient intakes of children and adults, it appears that school programmes that provide subsidized foods with good sources of protein to the poorest among school attendees will be cost effective. PMID- 1609184 TI - Optimum sample size determination in stratified case-control studies with cost considerations. AB - We investigate sample size determination for Cochran's test for stratified case control studies when samples of cases and controls are allocated to maximize the asymptotic efficiency of Cochran's test subject to fixed total cost with cost per control varying by strata. We consider two situations typical of strata-matched case-control studies: when one samples both cases and controls and when cases are given and one samples controls. In each situation we develop and study an asymptotic method for finding the sample size required for a specific power under the optimum allocation proposed by Nam and Fears. Also, for the second situation, we investigate an asymptotic method for determining the common ratio, k, in one to-k strata-matched case-control studies without cost consideration for a given power. When cases are given, neither the optimum nor the standard control sample sizes appear in a closed form; we present numerical methods for calculating these sample sizes and illustrate them with examples. We find the reduction in total cost obtained under the optimum allocation compared to standard allocation more pronounced as the differences in stratum-specific costs of sampling controls increase. PMID- 1609185 TI - Alternative parameterization of polychotomous models: theory and application to matched case-control studies. PMID- 1609187 TI - Latin square designs for crossover studies balanced for carryover effects. PMID- 1609186 TI - Estimating standardized parameters from generalized linear models. PMID- 1609189 TI - [Immunological selection of bone marrow donors]. AB - In the last twenty years bone marrow transplantation has become the treatment of choice for many hematological malignancies and immunologic defects. The ideal donor is a perfectly HLA-identical family member. Given the limited proportion of patients who can benefit of such a donor, unrelated bone marrow donors are increasingly being used. The immunological methods of selection used for siblings have been shown to be inadequate for the new type of donors. New techniques of molecular biology detecting a new micropolymorphism have been developed. This paper discusses the techniques and interpretations of the immunological tests of selection. PMID- 1609188 TI - [Bone marrow grafts. Introduction]. AB - Allogeneic bone marrow transplantation (BMT) is a therapeutic procedure which has a powerful antileukemic activity in addition to that of high dose radiochemotherapy. Its indications have progressively extended from leukemia to most malignant hemopathies. It allows in some of these disorders to increase the number of cures above that obtained by conventional chemotherapy and in others to cure diseases never curable by chemotherapy. Allogeneic BMT, in addition, found more recently many promising indications in the field of genetic disorders of the cellular systems derived from the hematopoietic stem cell. Autologous BMT (ABMT) is also efficient in the majority of malignant hemopathies. Its efficacy however is limited mainly to that of high dose(s) of radiochemotherapy. The efficacy of ABMT thus appears lower than that of allo BMT but in terms of survival this disadvantage is more or less compensated by its lower lethal toxicity. Its efficacy in comparison with that of conventional chemotherapy is still under study. The lethality induced by BMT itself, the risk of mortality due to the disease, the age of the patient and the degree of resistance of the disease to conventional therapies are, among others, crucial parameters to take into consideration for each specific case and of which will depend the quality and the duration of the patient's survival. PMID- 1609190 TI - [Bone marrow allograft in adults hemopathies. The Team of the Sterile Unit]. AB - For severe aplastic anemia and several malignant hemopathies allogeneic bone marrow transplantation is the only treatment with curative potential. This is the case for chronic myelogenous leukemia, the myelodysplastic syndromes and probably multiple myeloma and chronic lymphocytic leukemia. It seems also the best therapeutic option for young adults who suffer from acute leukemia and for whom an adequate family donor is available. We review here the main complications of the procedure. Their better knowledge and the way to prevent and to treat them has decreased the mortality and morbidity of this treatment which is mostly successful when applied on patients in the early phase of their disease. Recently, the availability of HLA typed registered volunteers has extended the applicability of allogeneic bone marrow transplantation for those patients who lack adequate familial donors. PMID- 1609191 TI - [Bone marrow autograft in malignant hemopathies. The Team of the Sterile Unit]. AB - Only in the last decade have autologous grafts begun to be studied extensively. Their most attractive feature is the avoidance of GVHD. However, GVHD has antitumoral effect on residual leukemic cells called "graft versus leukemia" effect and better understanding of this phenomenon explains the higher relapse rate after autologous bone marrow transplantation. New approaches such as cyclosporin--induced GVHD and IL-2 administration after autograft bring great expectations in this field. Colony stimulating factors and harvesting of peripheral stem cells help to reduce the duration of neutropenia. Finally, various techniques for marrow purging and hematopoietic cell isolation should make it possible to eliminate minimal residual disease. Recent results of autologous bone marrow transplantation in various malignancies are discussed. PMID- 1609192 TI - [Whole body irradiation]. AB - Total body irradiation produces a sufficient immunosuppression to prevent an allograft rejection. It can be used with chemotherapy as an "intensive" treatment aiming at the complete eradication of a malignancy--with the resulting bone marrow aplasia needing an autologous or allogeneic transplantation. In either case, a dose of some 10 Gy has to be delivered in the whole body, in one session at low dose rate or fractionated between several sessions. Such a dose is usually well tolerated--at any rate it does not carry too high a risk to contribute to induce an interstitial pneumonitis or a venous occlusive disease of the liver. The antitumoral efficacy of such limited dose is mainly important against very radiosensitive tumours--first of all leukemias and lymphomas. Yet some groups use also total body irradiation in the treatment of some solid tumours of dismal prognosis--for instance in case of advanced neuroblastomas or Ewing's sarcomas. PMID- 1609193 TI - [Ex-vivo treatment of a bone marrow graft]. AB - The use of bone marrow transplantation is increasing in the management of advanced cancers. In autologous bone marrow transplantation (ABMT), many investigators have attempted to purge the graft of residual tumor cells because of concern that reinfused tumor cells might contribute to relapse. The feasibility of various methods (exposure to chemical agents, monoclonal antibodies (MoAbs), toxins, dye, magnetic microparticles ... ) has been confirmed. In allogeneic bone marrow transplantation, clinical studies have related the prevention of graft-versus-host disease reaction through the partial depletion of T lymphocytes in the donor graft limited to 1 log to maintain a graft-versus-leukemia (GVL) effect. Similarly, the feasibility of different assays (soybean agglutinin, Moabs and magnetic microparticles) have been shown. However, the clinical benefit of BM purging remains to be demonstrated. For ABMT, only recent data on B-cell lymphoma and leukemia strongly support the clinical usefulness of an ex-vivo purging. For allogeneic BMT, one question remains controversial: is T lymphocytes depletion the best method for GVHD prevention? PMID- 1609194 TI - [Pulmonary opacity and heart transplant. Primary pulmonary lymphoma (large-cell anaplastic)]. PMID- 1609195 TI - [The role of the nurse in services for drug dependents]. AB - Aim of the work is to take into account the role of nursing in Drug Dependence Units, on the bases of the experience acquired by the Authors at the Servizio di Neuropsicotossicologia in Dolo (Venice). Two working patterns are distinguished, which have to be integrated in daily practice: 1) the fulfillment of "technical" tasks, giving particular importance to drug administration and laboratory data control (for chemical and toxicological testing); 2) the relationship with patients, with reference to the distinction between diagnostic function. It is particularly stressed that the nurse is the first staff operator to be brought in contact with patients and to follow them during the therapeutic program. The relationship with psychologically disturbed patients can be very hard and often too much involving. It is therefore important for nurses working in this field to have a specific training. PMID- 1609196 TI - [Epidemiological study of the health-disease experience of patients with myocardial infarct]. AB - GISSI-Nursing is a multicentre research project whose main characteristics are summarized in the title "Epidemiological study of the perception and experience of health and illness in the patient with acute myocardial infarction". A large sample CCU nursing staffs (85 out of the country approximately 230) agreed to take part in the protocol, which has become operational on March 1, 1991. The study aims at producing a longitudinal profile (from the post acute phase up to 6 months after the index event) of the way patients live the situations which procede accompany, follow the acute myocardial infarction. The size of the foreseen population (around 2500 patients) and the first han involvement of a care group of nurses in the planning and the management of the study may be seen as a promising set up for producing not only interesting new data but also original methodological insight into the research role of nurses. PMID- 1609197 TI - [Transplants]. PMID- 1609198 TI - [To be as they are]. PMID- 1609199 TI - [Law and rights]. PMID- 1609200 TI - [The Kangaroo]. PMID- 1609202 TI - [The quality of life for the elderly. A descriptive study]. PMID- 1609201 TI - [The means for preventing nosocomial infection (II)]. PMID- 1609203 TI - [Oxygen therapy]. PMID- 1609204 TI - [We are facing one of the great public health problems of our age. Interview by M. J. Nadal]. PMID- 1609205 TI - [Delivery with epidural anesthesia (II). Nursing care]. PMID- 1609206 TI - [Holistic health. The consequences of a mistaken interpretation]. PMID- 1609207 TI - [The social health indicators in psychogeriatrics]. PMID- 1609208 TI - [The percutaneous catheter: the solution]. PMID- 1609209 TI - [Noninvasive arterial pressure monitors]. PMID- 1609210 TI - [The plan of study for nursing diploma holders]. PMID- 1609211 TI - [Continuing education. 70. Adaptation to extrauterine life]. PMID- 1609212 TI - [Biopathology of renal cancer in adults]. AB - Most renal cancers are clear cell adenocarcinoma. The classification is based on the tumor size, the renal vein and lymph node involvement, and metastases. Renal cancer originates from the proximal convoluted tubule. The murine Renca tumor and the Wistar-Lewis rat renal adenocarcinoma are experimental models which well reproduce the evolution of the human renal cell carcinoma. They allow the study of the effect of chemotherapeutic agents, of lymphokines and of transfected cytokines. However, experimental models have limited value. PMID- 1609213 TI - [Epidemiology and detection of renal cancer in adults]. AB - The incidence of renal carcinoma in France is 7 for 100,000 men and 3 for 100,000 women. Most cases are found in patients in their sixties or seventies. With the exception of the rare Von Hippel-Lindau disease, the only risk factor is tobacco smoking. The circumstances in which renal carcinoma is discovered have changed during the last few years: 1 out of 2 renal carcinomas are still diagnosed on their classical signs (essentially haematuria), but almost as many other cases are incidentally and unexpectedly detected by abdominal ultrasonography when the carcinoma is totally asymptomatic. The conventional attitude towards these fortuitously discovered renal tumours is the same as for asymptomatic tumours, i.e. widened nephrectomy. In case of small tumours a few centimetres wide, 20% of which are benign, it may be useful to wait a few months and reevaluate the situation prior to considering surgery. In elderly and asymptomatic patients the immediate surgical risk/long-term benefit ratio must be carefully weighed. PMID- 1609214 TI - [Imaging of renal cancer in adults]. AB - In its typical form renal carcinoma shows at imaging as a solid, heterogeneous and vascularized mass deforming the kidney; its CT scan appearance is usually very suggestive. Atypical forms (small or cystic carcinomas, large carcinomas with exorenal extension, haemorrhagic carcinomas) mainly raise problems of characterization; the lesional image is always suspicious at CT or combined US, CT and MRI examinations. The detection of small tumours primarily rests on CT with contrast injection, a technique which is more sensitive (94%) than all other techniques. Among non-tumoral lesions which may look like renal carcinomas, some pseudotumoral inflammatory lesions and suspicious atypical cysts often require histological examination. With the exception of angiomyolipoma with its fat content detectable at CT or MRI, there is no truly specific criterion to differentiate benign tumour from cancer. The diagnosis of renal carcinoma extension primarily rests on MRI. In a number of cases the results are so inadequate for the study of renal veins and caval vein that a complementary exploration of these veins by Doppler ultrasonography or MRI must be requested. PMID- 1609215 TI - [Surgical treatment of renal cancer in adults]. AB - The curative cell carcinoma is surgery and consists of a radical nephrectomy. Pre operative assessment must be complete. Indications are extensive because nephrectomy allow, even in evaluated forms, a long and comfortable survival. The incidental discovery of renal cell carcinoma is more and more frequent. It allows limited surgery and should be followed by higher survival rates. PMID- 1609216 TI - [Renal cell cancer: oncogenes and tumor suppressor genes]. AB - Recently, there has been a significant increase in the knowledge about the molecular basis of renal cell carcinoma. Its sporadic form is characterized by a deletion on the short arm of chromosome 3, even for localized stages. The same genetic abnormality is found in renal cell carcinomas associated with the von Hippel-Lindau disease. Such findings strongly suggest the presence of a common tumor suppressor gene which seems involved in the genesis of sporadic renal cell carcinoma and in the predisposition of hereditary cancers. Other tumor suppressor genes located on other chromosomes, as well as over expression of growth factors, seem to be related to the progression of this malignancy. Further studies of the molecular events associated with cellular transformation should help to better understand the behavior of such cancers and to find new therapeutical approaches. PMID- 1609217 TI - [Treatment of renal cancer in adults with interleukin 2]. AB - Interleukin 2 is active in metastatic renal adenocarcinoma which is usually considered as a chemoresistant tumour; 20 to 30% objective responses, including 5 to 10% complete remissions, are reported using various treatment schedules. Toxicity, though of great concern, is now controlled and IL2 is mostly used in standard oncology units or as an out-patient subcutaneous treatment. Even if IL2 is now a registered drug in France, many questions remain however, regarding the optimal schedule and dose, the interest of combining IL2 with interferon alpha or the predictive factors of response of this therapy. PMID- 1609218 TI - [Therapeutic strategy in metastatic renal cancer]. AB - Prognostic factors have been described in metastatic renal cell cancer: performance status, weight loss, elevated erythrocyte sedimentation rate, presence of liver metastases. The treatment for a patient with good prognosis consists of: surgical exeresis of solitary metastasis, immunotherapy by either interferon or interleukin 2. Treatment in case of a rom prognosis is a combination of supportive care, orthopedic surgery for pathologic fracture or medullar compression, antalgic radiotherapy, embolization, nephrectomy for hematuria, and analgesic treatments. PMID- 1609219 TI - [Arterial remodeling in hypertension. An adaptive phenomenon with severe consequences]. PMID- 1609220 TI - [Alcoholism and somatic complications of excessive alcohol drinking. Do genetic predispositions exist?]. PMID- 1609221 TI - [Lofgren syndrome. Radio-clinical diagnosis or investigations?]. PMID- 1609222 TI - [Hepatic metastasis of non-colorectal cancers. Results of surgical treatment]. AB - To evaluate long-term results after curative hepatic resection for metastases from non-colorectal cancers, eleven studies published between 1978 and 1991 were reviewed. Data from 255 patients were available. Among these 255 patients, hepatic metastases were originating from 35 different primitive tumors. Breast cancers were the most frequent primitive tumors (n = 34, 13%). Following hepatic resection, Wilm's tumors and endocrine tumors gave the best results (five-year survival rate superior to 50%). Despite hepatic resection, melanomas and pancreatic cancers remained of poor prognosis. In breast cancers, when hepatic surgery was associated with adjuvant chemotherapy, the five-year cumulative survival was 16%. For leiomyosarcomas, gastric adenocarcinomas and gallbladder cancers few cases of prolonged survival have been recorded. These results suggest that in a selected group, surgery could be contemplate with chance of cure. Multicentric studies and/or a national register, would allow to improve the selection of patients and to optimize the surgical approach. PMID- 1609223 TI - [Psychiatry in a fetal medicine department]. PMID- 1609224 TI - [Anticoagulants (heparin, antivitamins K, principles and rules of use)]. PMID- 1609225 TI - [Vaquez disease. Diagnosis, principles of treatment]. PMID- 1609226 TI - [Malignant melanoma. Pathological basis of the prognostic evaluation]. PMID- 1609227 TI - [Bacterial spondylodiscitis. Etiology, diagnosis, course, prognosis and treatment]. PMID- 1609228 TI - [Chest pain. Diagnostic orientation]. PMID- 1609229 TI - [Gout. Epidemiology, physiopathology, diagnosis, course, prognosis, principles of treatment]. PMID- 1609231 TI - [Dental malocclusions. Diagnostic orientation]. PMID- 1609230 TI - [Chronic obstructive pulmonary diseases and their complications. Epidemiology, etiology, physiopathology, diagnosis, course, prognosis, principles of treatment, including prevention]. PMID- 1609232 TI - [General states of rheumatoid polyarthritis]. PMID- 1609233 TI - [Reflexions on the evaluation of the quality of life in rheumatology]. PMID- 1609234 TI - [Camptocormia in the elderly. A new entity by paravertebral muscle involvement?]. AB - "Camptocormism" in the elderly is an acquired kyphosis which increases during walking and is totally reducible in dorsal horizontal position in two thirds of cases. The authors report 16 cases of camptocormism in patients with a mean age of 76 (12 women, 4 men). Camptocormism was accompanied in 5 cases by an extrapyramidal syndrome, in 3 cases by articular chondrocalcinosis, in 1 case by giant cell arteritis and in 1 by rheumatoid arthritis. There was no inflammatory syndrome and muscle enzymes were raised in only 4 cases. Electromyogram of the paravertebral muscles was pathological in 5 cases, with neurogenic changes in 4 cases and a myogenic type tracing in one. CT scan or magnetic resonance imaging showed evidence in all cases of atrophy with fatty involution of the paravertebral muscles. Biopsies of the paravertebral muscles revealed moderate mononuclear cell infiltrates in 4 cases with similar abnormalities in peripheral muscles. Corticosteroids had a beneficial effect in 11 cases out of 13 and the most prolonged results were seen after bolus doses of methylprednisolone. These findings suggest that camptocormism in the elderly could be linked to inadequacy of the paravertebral muscles or, in certain cases, to interstitial myositis. PMID- 1609235 TI - [Incidence of signs indicating psoriatic rheumatism in radiological involvement of fingers and toes. Apropos of 193 cases of psoriatic arthropathy]. AB - On the basis of 193 cases of psoriatic arthropathy, the authors sought the incidence and rapidity of onset of signs suggestive of this type of rheumatic disorder when there are radiological lesions of the fingers and toes. They conclude that when such radiological lesions exist, signs suggestive of psoriatic arthropathy are frequent (90%), early (85% of cases of psoriatic arthropathy present for less than 5 years) and predominantly involve the distal parts of the fingers and toes (85.5%). The authors consider that the signs which distinguish psoriatic arthropathy from rheumatoid arthritis are due to an extrasynovial process of enthesopathic origin. PMID- 1609236 TI - [Therapeutic maintenance dose with methotrexate in rheumatoid polyarthritis. Prospective study of 191 cases]. AB - One hundred and ninety one patients with rheumatoid arthritis were included in an open prospective trial with the aim of evaluating the acceptability, efficacy and therapeutic maintenance levels of methotrexate. The mean treatment duration was 19 +/- 13.2 (3-58) months and the mean weekly dose of methotrexate 10.2 +/- 0.2 mg. Analysis of the 191 patients by intention to treat showed a statistically significant improvement in all clinical parameters as well as a significant fall in sedimentation rate with a corticosteroid-sparing effect. The therapeutic maintenance level of methotrexate was 73% at one year, 65% at 2 years and 46% at 5 years. Adverse reactions occurred in 71 patients (37.1%) including 30 who stopped methotrexate permanently as a result. With cautious and strict patient selection, methotrexate could be used in RA as basic treatment of first choice. PMID- 1609237 TI - [Value of false profile of the pelvis in the monitoring of total hip prosthesis]. AB - The authors used a retrospective series of cases of total hip replacement with a follow-up of between 6 and 12 years, including 10 undergoing reoperation for slipping of the prosthesis, to define the value of the false lateral view of the pelvis in the monitoring of such patients. This view provides earlier detection than AP views of wearing of polyethylene which manifests itself by penetration of the femoral head into the acetabular implant. This penetration, which can be measured radiologically, is better visualised in the false lateral view of the pelvis for simple reasons of radiological incidences. The false lateral view of the pelvis has another use in the monitoring of total hip replacements. It enables visualisation of the posterior part of the acetabulum which is generally the site of first appearance of the earliest signs of slipping in the form of a thin line. PMID- 1609238 TI - [Synovectomy in the realignment-stabilization of the rheumatoid wrist. Apropos of a series of 104 cases with average follow-up of 5 years]. AB - The authors studied a series of 104 rheumatoid wrists, stages II, III or IV according modified Larsen's grading, treated between 1980-1988 by synovectomy realignment stabilization. The mean follow-up period was 5 years. The operation presents different steps which have an additive effect and must be associated in order long term clinical and radiological stability. They associated: extensor tendons and articular synovectomy stabilization of the distal radio ulnar complex by Sauve-Kapandji's operation, tendon transfert: the extensor carpis radialis longus is transferred on the extensor carpi radialis brevis the extensor carpi ulnaris is relocated with posterior annular dorsal ligament plasty. Results concerning relief of pain were very clear because the patients presented either complete relief of pain (73%) or only intermittent occasional pain. The overall active range of motion is nearly the same, when compared pre- and post-operative ratings. In general the patients who presented good pre-operative mobility usually improved them and the others preserved them. Larsen's radiological grading was modified by the authors to include instability's criteria in frontal and sagittal plane. Carpal height remained stable (75% less than or equal to 1 mm), ulnar deviation has never overreached 3 mm, radial deviation was not modified in 50% of cases. They found only 4 wrists presenting a stage II radiological grading with an evolution to the stage III and 12 of the stage III grading became stage IV. The instable type of the stage IV was stabilized by a surgical radiolunate arthrodesis. The stabilized type was nearly not modified. The different steps of operation (articular and tenosynovectomy, carpus stabilization and realignment with stabilization by stabilization of the radio ulnar complex joint using Sauve-Kapandji operation, tendons transfers and dorsal retinacular plasty) have an additive effect in achieving relief of pain with preservation of the pre-existing mobility. The stabilization of the radio ulnar complex by the Sauve-Kapandji operation constitutes a new approach in rheumatoid arthritis published by the author in 1985 and in our opinion appears to be simple and is very efficient in stabilizing wrist immediately, thus allowing early rehabilitation of these patients. Long term stability is affirmed by clinical and roentgenologic follow-up and globally a painless wrist, a preservation of the pre operative motion and a stabilization in frontal and sagittal plane is obtained. PMID- 1609239 TI - [Post-traumatic osteolysis of the distal extremity of the clavicle. Anatomopathological study of 2 cases]. AB - Two patients with post-traumatic osteolysis of the distal end of the clavicle undergoing surgery 5 months and 22 months respectively after the initial trauma were evaluated histopathologically. The lysed zone was replaced by tissue of fibrous appearance, with little blood supply and non-inflammatory, the presence of which could be suspected by magnetic resonance. The synovial membrane, non inflammatory but hypervascularised, participated in the process but did not appear to be directly responsible for the osteolysis. The osseous tissue of the patient, operated upon early, showed signs of osteoclastic resorption but there was neither stasis, vasodilatation nor signs of osteogenesis. These various findings suggest that post-traumatic osteolysis of the distal end of the clavicle does not result from local ischemic events. These appearances seem identical to those described in multifocal primary osteolysis, the cause of which also remains unknown. PMID- 1609240 TI - [Temporomandibular joint and rheumatoid polyarthritis. Correlations between clinical and tomodensitometric abnormalities]. AB - Clinical and CT scan abnormalities of the temporomandibular joint in rheumatoid arthritis have been little studied in the literature. The temporomandibular joint was examined clinically and by CT scan in 26 patients with rheumatoid arthritis and 26 controls. In the rheumatoid arthritis group, 61.2% of patients had physical signs of temporomandibular disease as compared with 42.3% of the controls. 88.4% of rheumatoid arthritis had erosive or geodic lesions of the temporomandibular joint by CT scan as compared with 57.6% of the controls (p less than 0.05). The temporomandibular clinical score was not correlated with CT scan score in rheumatoid arthritis. CT scan score was correlated with the number of basic drugs used, rheumatoid factor levels and radiological scores of the hands and cervical spine. The authors feel that the only CT scan abnormalities specific to rheumatoid arthritis consist of erosive and geodic lesions of the mandibular condyle, that there is no correlation between clinical and CT scan abnormalities of the temporomandibular joint in rheumatoid arthritis and that the extent of destructive lesions of the temporomandibular joint by CT scan in rheumatoid arthritis is closely correlated with the severity of the disease. PMID- 1609241 TI - [Lumbo-radicular pain caused by epidural lipomatosis in an obese patient: recovery after hypocaloric diet]. AB - The case reported concerns an obese patient suffering from lumbo-radicular intermittent claudication due to lumbar epidural lipomatosis. Compression was revealed by magnetic resonance imaging which showed the existence of a hypersignal in weighted sequences in T1 situated in the epidural space and narrowing the dural sheath. Three cases of lumbar epidural lipomatosis related to obesity have already been described. Treatment in all three was surgical with the result assessed as good in one case and poor in two. The interest of the present case is demonstration of the cause and effect relationship between epidural lipomatosis and obesity as shown by complete restoration of the epidural space after a calorie-controlled diet, and the possibility of successful treatment by this technique. PMID- 1609242 TI - [Treatment of Still's disease with bolus methylprednisolone. Retrospective study of 7 patients]. AB - The problems raised by the treatment of Still's disease in the child or adult led the authors to evaluate the short term clinical efficacy of bolus doses of methylprednisolone. Seven patients were given 12 boluses, followed by oral corticosteroids at 5 to 10 mg in 9 cases out of 12. Still's disease was active in all cases. A frank clinical improvement was seen on the fourth day. The response duration was 3 weeks to 20 months, with a mean follow-up period of 7 months. There were 3 early relapses, 5 late relapses between 2 and 20 months and 4 patients are still in remission at 5, 6, 15 and 19 months. There were no immediate adverse reactions. These results suggest the usefulness of boluses of methylprednisolone in exacerbations of Still's disease, avoiding the disadvantages of high dosage daily corticosteroids. PMID- 1609243 TI - [Osteodensitometry: apropos of the ANDEM report]. PMID- 1609245 TI - Urotherapy in children with dysfunctional bladder. PMID- 1609244 TI - Urinary incontinence in children: suggestions for definitions and terminology. AB - The definition of childhood urinary incontinence, used here, is leakage of at least 1 ml of urine, at least once a week, in a child from 5 years of age. The types of incontinence are defined as detrusor incontinence (daytime urge incontinence and night-time enuresis), sphincter incontinence (presenting clinically as stress incontinence in the less serious form, as continuous dribbling of urine in the more serious one), and combined incontinence (the combination of detrusor hyperactivity and sphincter incompetence found in many children with neurogenic bladder dysfunction). Urinary incontinence in children is subdivided into night-time (most common) and daytime incontinence. Day wetting is aetiologically subdivided into incontinence due to organic or functional causes. The organic causes can be either structural (e.g. epispadias) or neurogenic. Functional day wetting is incontinence not caused by disease, injury or congenital malformation, and is almost always urge incontinence due to an unstable bladder. Unstable bladder in children may activate the sphincteric guarding reflex, leading to dyscoordination between the sphincter and the detrusor, and, eventually, overdistension of the bladder with a reduced contraction power of the detrusor ('lazy bladder'). Ultimately, Hinman's syndrome (non-neurogenic neurogenic bladder) may develop. The term enuresis should be used to denote incontinent, complete micturitions and should thus be reserved for bedwetting and giggle enuresis. PMID- 1609246 TI - Functional daytime incontinence: pharmacological treatment. AB - The basis for the treatment of functional daytime incontinence in children is the bladder regimen, i.e. to teach the children to void regularly by the clock. Drug treatment may be needed as an adjunct to the regimen in children with gross detrusor instability. There is no evidence from properly controlled studies that tricyclic antidepressants or anticholinergic drugs are of value for the child with daytime wetting. Terodiline is a new drug combining anticholinergic and calcium-blocking effects. In two randomized, double-blind studies of terodiline compared with placebo in children with urge incontinence (i.e. functional day wetting), continence improved significantly over placebo in the terodiline group. Only a few mild adverse reactions were noted. Children with symptomatic urinary tract infection and day wetting should receive chemotherapy, but covert bacteriuria should best be left untreated. There is no evidence that eradication of the bacteriuria improves continence. Instead, there is a great risk of symptomatic recurrence of the urinary tract infection after antibacterial treatment. PMID- 1609247 TI - Management of the incontinent child in general practice. The paediatric urologist's viewpoint. AB - Except for children with neurological disease or major structural anomalies, the burden of managing childhood urinary incontinence in the UK falls predominantly upon general practitioners and local specialists. Because they see relatively few cases and have many other calls upon their attention, their postgraduate education on this topic must be succinct and basic; this article is based upon such advice. The organic causes of childhood urinary incontinence are discussed as also the clinical features and basic investigations (principally ultrasonography) which call attention to them. The various clinically recognisable patterns of functional voiding disorders are described with emphasis on the commonest, urge incontinence. Based on these considerations a scheme is recommended which aims to minimise necessity for secondary or tertiary referral, yet at the same time ensures that organic disease or severe functional voiding disorders are not overlooked. PMID- 1609248 TI - Management of the incontinent child in general practice. The paediatrician's viewpoint. PMID- 1609249 TI - Structural incontinence. PMID- 1609250 TI - Management of urinary incontinence in neurogenic bladder. AB - The treatment of children with urinary incontinence caused by a neurogenic bladder presents a challenge to the paediatric urologist. Between 1965 and 1989, 527 patients with neurogenic bladder were treated and followed-up in the Department of Paediatric Urology of Debrousse Hospital. Of these, 46 were submitted to continent cystostomy, 39 to urinary artificial sphincter and 177 to clean intermittent catheterization (CIC). This last treatment is of paramount importance in girls and can be associated with complementary procedures if cervico-urethral resistance and/or bladder compliance are poor. Urethral lengthening (Kropp's procedure) in combination with CIC represents a major means of providing dryness in girls. Our technique of urethral lengthening is detailed and the place of CIC among other incontinence treatment is discussed. PMID- 1609251 TI - Functional daytime incontinence: definitions and epidemiology. AB - The definition of childhood urinary incontinence, used here, is leakage of at least 1 ml of urine at least once a week in a child from 5 years of age. Functional day wetting is incontinence not caused by disease, injury or congenital malformation, and is almost always urge incontinence due to an unstable bladder. The following figures for prevalence are quoted from the Gothenburg study of 35567-year-old school entrants. Any kind of urinary incontinence at least once a week was reported by 6% of the children. Day wetting at least once a week was found in 3.1% of the girls and 2.1% of the boys. Most of the day wetting children also had urgency which was reported in 82% of the girls and 74% of the boys. Bedwetting at least once a week was reported by 2.9% of the girls and 3.8% of the boys. The bedwetting was monosymptomatic (no additional symptoms, no day wetting) in 39% of the girls and 59% of the boys with nocturnal enuresis. Combined daytime and night-time incontinence was reported by 17% of the children, while 22% wet only by day, and 61% only by night. None of the 3556 children had a previously undetected organic cause for their incontinence. There is a strong association between bacteriuria and day wetting in girls, but not in boys. We do not know whether the bacteria cause the disturbance of bladder function, or vice versa. The cause and effect may work in both directions. PMID- 1609252 TI - Urinary incontinence in children and associated problems. AB - Urinary tract infections are common during childhood. The association to bladder dysfunction was studied in two different populations of children. First, the prevalence of UTI in 3553 7-year-old schoolchildren with and without incontinence was assessed. Isolated bed wetting was not associated with UTI. In combined night and day wetting or day wetting alone there was a strong correlation to previous UTI. Secondly, the majority of girls with covert bacteriuria had clinical and urodynamic evidence of bladder dysfunction. PMID- 1609253 TI - Functional daytime incontinence: clinical and urodynamic assessment. AB - Assessment of children with daytime wetting starts with the distinction between 'enuresis diurna' and 'functional incontinence', incontinence being defined as any form of wetting caused by bladder/sphincter dysfunction. Standard history taking does not allow for a sharp enough distinction: pertinent questions have to be asked about daytime wetting, night-time wetting, micturition, and about urge and reactions to urge. By using urodynamics to expose the pathophysiology behind the patterns of bladder/sphincter dysfunction, these questions were formulated and validated in a series of 156 children, referred with persistent daytime wetting to a programme for cognitive bladder training. With history-taking organized into a simple questionnaire, complemented by urodynamics, four patterns of bladder/sphincter dysfunction emerged: urge syndrome, staccato voiding, fractionated and incomplete voiding, and lazy bladder syndrome. A strong correlation was found between recurrent urinary tract infections and non neuropathic bladder/sphincter dysfunction, implying that detection and treatment of bladder/sphincter dysfunction is essential in every child with recurrent urinary tract infections, especially in the presence of vesico-ureteral reflux. PMID- 1609254 TI - Monosymptomatic bedwetting. AB - An update of the pathogenesis and treatment of monosymptomatic bedwetting is presented. This frequently occurring entity seems to have a multifactorial pathogenesis incorporating arousal disturbances and disturbances to the circadian rhythm of diuresis modulating hormones. It has recently been substantiated that the bladder reservoir function in monosymptomatic bedwetting is normal. This is further underlined by the fact that treatment of instability of the bladder has proven futile. In a substantial part of the monosymptomatic bedwetters the changes in circadian rhythm of antidiuretic hormone can be counteracted by desmopressin diacetate (DDAVP), which abolishes the symptom in more than 2/3 of the patients. Monitoring circadian rhythms of arginine vasopressin (AVP) and treatment with DDAVP have led to increased understanding of the pathogenesis of monosymptomatic bedwetting and opened new fields of investigation. PMID- 1609255 TI - Video-urodynamic studies of minor voiding dysfunctions in children: an overview of 13 years' experience. AB - By the definition 'minor voiding dysfunctions' is understood children with a history of frequency, urgency, daytime wetting, squatting, and infrequent voiding, singly or in combination. Urinary tract infections (UTI) are often present but symptoms must also be present when the children are free of infection. The upper urinary tract is generally normal or has minor anomalies. Any evidence of infravesical obstruction, frank or occult neurogenic bladder, or emotional disturbances must be excluded. In this study we report 13 years' experience of video-urodynamic evaluation in children with minor voiding dysfunctions, with special reference to clinical information, morphofunctional correlations, relationship with recurrent UTI, vesico-ureteric reflux and dilatation of the upper urinary tract. According to our experience we estimate that about 60% of the patients evaluated in this study would not require a video urodynamic evaluation today. PMID- 1609256 TI - Ambulatory urodynamics: preliminary experience with vesico-urethral holter in children. AB - Detrusor function was evaluated by vesico-urethral holter (VUH), a computerized recording system (Urodec 500), in 17 children with lower urinary tract dysfunction. Eight had neurogenic bladders, eight had minor voiding dysfunction, and one was incontinent after posterior urethral valve ablation. VUH was technically satisfactory in, and acceptable to, all patients. It was more accurate in evaluating the type of urinary tract dysfunction than conventional urodynamics in 25% of the male patients and in 32.5% of the female patients. PMID- 1609257 TI - Functional daytime incontinence: non-pharmacological treatment. AB - In children with 'functional incontinence', defined as any form of (daytime) wetting caused by non-neuropathic bladder/sphincter dysfunction, most signs and symptoms are rooted in habitual non-physiological responses to signals from bladder and urethra. These responses develop at toddler age, when children learn how to remain dry. Once they have become a habit, incomplete bladder emptying and recurrent urinary tract infections come into play, reiterating the non physiological responses into fixed patterns of bladder/sphincter dysfunction with functional incontinence as the leading symptom. Non-pharmacological treatment of functional incontinence implies relearning and training the normal responses to signals from bladder and urethra: a cognitive process, with perception of the signals reinforced by biofeedback. This type of treatment is best combined with long-term chemoprophylaxis. Severe cases will benefit from anticholinergic drugs, as adjuvants to the training programme. Urodynamics play a crucial role in documenting the specific patterns of incontinence and in providing biofeedback. For a successful programme, psychological screening of the children is indispensable. PMID- 1609258 TI - [Agrarian structure development in Switzerland from the viewpoint of agrarian politics and current international negotiations]. PMID- 1609259 TI - [Intersexuality in hornless XX-goats: pathological findings in 2 young pseudobucks, 3 young bucks with urethral diverticula and 2 pseudohermaphroditic kids]. AB - Dealing with the subject "polled goats intersexuality", whose problems are discussed, we studied the pathology of 7 3-month old XX-kids: 2 pseudomales, 3 males with urethral diverticulum (1 animal with 2 U.D.), and 2 testicular pseudohermaphrodites. Four horned male kids of comparable age were used as control. Urethral diverticula, seen now and then in local breeds, i.e. in "chamois-colored" mountain goats, Saanen, and Toggenburg goats, are rather unknown and only sporadically reported abroad. In agreement with previous histological studies, the testes were hypoplastic, the spermatogonia absent. In no case ovarian tissue was found. The Leydig cells appeared to be functionally active. The selection of an experimental flock of intersex-free polled goats is proposed. PMID- 1609260 TI - [Secondary placental retention with purulent necrotising myometritis asa consequence of a birth injury in cattle]. AB - A four year old cow with an enlargement of the uterus of unknown cause was submitted to the clinic. The cow had a pyonecrotizing myometritis and placental retention following an injury of the birth canal. The final diagnosis was only made after pathological examination. PMID- 1609261 TI - Cardiac transplantation in Scotland. PMID- 1609262 TI - HIV and AIDS update--1992. PMID- 1609263 TI - Planning for the needs of people with dementia. PMID- 1609265 TI - Microangiopathy as a prognostic indicator in diabetic patients suffering from acute myocardial infarction. AB - Diabetic patients have an increased mortality following myocardial infarction (MI) due to left ventricular failure rather than larger infarcts or dysrhythmias. As this may be due to diabetic microangiopathy affecting the myocardium, we have examined the case records of diabetic clinic patients admitted to the Coronary Care Unit (CCU) with proven MI and compared the hospital outcome of those with and without retinopathy or nephropathy, i.e. markers for generalised microangiopathy. Sixty four consecutive records were traced, for the period when diabetic treatment policy was standardised in CCU, 24 patients had retinopathy (7 proteinuria). When compared to non-retinopathy patients they had similar ages 67 +/- 12 yr [+/- SD] v 63 +/- 9yr) but were of longer duration of diabetes p less than 0.05). There were no differences between the groups in size or site of infarct, previous infarct or hypertension history, blood glucose on admission or diabetic treatment before or after admission. Death occurred in 29% of retinopathy patients compared to 3% of non-retinopathy patients (p less than 0.01). Cardiac failure complicated 75% of retinopathy patients and 25% of non retinopathy patients (p less than 0.001). Dysrhythmia occurred in 50% and 33% of patients respectively (P = NS). Nine patients had clinical peripheral vascular disease and five of these died. This study, of a selected group of diabetic clinic attenders admitted to CCU with acute MI, demonstrates that microangiopathy and peripheral vascular disease are important prognostic factors in determining hospital outcome as these patients are at increased risk of cardiac failure and death. PMID- 1609264 TI - Neutrophil count and activation in vascular disease. AB - An elevated peripheral leucocyte count is associated with an increased risk of myocardial infarction and progression of coronary artery disease. The aim of this study was to determine neutrophil count and activation, measured as an increase in plasma neutrophil elastase, in patients with stable ischaemic heart disease, insulin-dependent diabetes mellitus and essential hypertension compared with a comparable group of control subjects. Neutrophil count and neutrophil elastase were raised significantly for patients with ischaemic heart disease (p less than 0.005; p less than 0.002), diabetes mellitus (p less than 0.001; p less than 0.01) and hypertension (p less than 0.05; p less than 0.0001) respectively compared to the control subjects. Neutrophil elastase did not correlate with subject age or leucocyte count. This study confirms the association between leucocyte count and vascular disease, and is consistent with neutrophil activation contributing to the progression of vascular disease. PMID- 1609266 TI - A review of caesarean sections at 30 weeks gestation or less in the west of Scotland 1988-1989. AB - A retrospective study was carried out of caesarean sections at 30 completed weeks of gestation or less between 1/1/88 and 31/12/89 in Glasgow and The West of Scotland. One hundred and thirty-three caesarean sections were carried out resulting in 150 babies. Fifteen (11.3%) of these were classical sections. There were 30 neonatal deaths. The perinatal mortality rate was 170 per 1000. Survival was related to increasing gestation from 27 weeks onwards and also to birthweight from 900 grams onwards. In-utero transfers fared badly with seven out of 21 babies (33%) failing to survive beyond the neonatal period. Although survival continues to improve in newborns, the use of caesarean section should still be viewed with caution as the benefits in the very premature situation with regard to infant survival may be outweighed by the increased maternal morbidity both in the present pregnancy and future pregnancies. PMID- 1609267 TI - Seasonal and climatic variation in cholesterol and vitamin C: effect of vitamin C supplementation. AB - Vitamin C (ascorbic acid) is an important anti-oxidant which may help to reduce free radical damage and atheroma formation in blood vessels. In a study in which a group of healthy volunteer subjects were followed up for 12 months and a group of patients with vascular disease taking Vitamin C supplements were followed for 23 months, we confirmed previous findings of seasonal variations in ascorbic acid and cholesterol and have shown an inverse relationship between leucocyte ascorbic acid and serum cholesterol levels. In healthy control subjects the increase in ascorbate and fall in cholesterol during the summer months was reversed when the weather changed to a more winter pattern, presumably due to dietary alterations. We found that ascorbic acid levels were lower in patients with peripheral vascular disease and that although normal ascorbic acid levels were achieved with Vitamin C supplementation, when supplements were stopped at the height of a normal summer, there was a fall in ascorbic acid and a rise in serum cholesterol to winter levels. Given these findings we suggest that patients with vascular disease should have Vitamin C supplements throughout the year. PMID- 1609268 TI - Use of beta-blockade in a patient with phaeochromocytoma and asthma. AB - This case report describes a patient with co-existing phaeochromocytoma and bronchial asthma. She had no asthmatic symptoms at the time of diagnosis of phaeochromocytoma; her asthma recurred after adrenalectomy. Despite concern about the use of a beta-blocker in a patient with asthma, pre-operative tachycardia was successfully treated with the beta-1-selective adrenoreceptor antagonist, metoprolol. PMID- 1609269 TI - Small bowel adenocarcinoma complicating Crohn's disease. AB - Crohn's disease of the small intestine is usually managed by medical therapy with surgery being reserved for obstruction or fistula formation. A patient is described who developed small bowel obstruction due to an adenocarcinoma of the ileum after over twenty years of medical therapy for Crohn's disease, originally diagnosed at a laparotomy for acute abdominal pain. The possibility of malignancy in such long-standing disease should be considered. PMID- 1609270 TI - Scottish women medical pioneers: Manchuria 1894-1912. AB - In Edwardian Britain, less than 2% of all registered medical practitioners were women. Yet during that era, women played a significant role in providing medical care and education in what were lonely, harrowing and difficult conditions in the Third World. This is the story of how a group of Scottish women doctors brought Western medicine to a remote region of Manchuria between 1894 and 1912. PMID- 1609271 TI - Exaggerated carcinogenicity of chemicals. PMID- 1609272 TI - Who controls a researcher's files? PMID- 1609273 TI - Biting back at Lyme disease. PMID- 1609274 TI - A surprise animal model for AIDS. PMID- 1609275 TI - Chimps protected from infected cells. PMID- 1609276 TI - Studies set to test competing theories about early infection. PMID- 1609277 TI - Three-dimensional solution structure of human interleukin-4 by multidimensional heteronuclear magnetic resonance spectroscopy. AB - The three-dimensional solution structure of recombinant human interleukin-4, a protein of 133 residues and 15.4 kilodaltons that plays a key role in the immune and inflammatory systems, has been solved by multidimensional heteronuclear magnetic resonance spectroscopy. The structure is dominated by a left-handed four helix bundle with an unusual topology comprising two overhand connections. The linker elements between the helices are formed by either long loops, small helical turns, or short strands. The overall topology is remarkably similar to that of growth hormone and granulocyte-macrophage colony stimulating factor, despite the absence of any sequence homology, and substantial differences in the relative lengths of the helices, the length and nature of the various connecting elements, and the pattern of disulfide bridges. These three proteins, however, bind to cell surface receptors belonging to the same hematopoietic superfamily, which suggests that interleukin-4 may interact with its receptor in an analogous manner to that observed in the crystal structure of the growth hormone extracellular receptor complex. PMID- 1609278 TI - Triple helix-specific ligands. AB - A triple helix is formed upon binding of an oligodeoxynucleotide to the major groove of duplex DNA. A benzo[e]pyridoindole derivative (BePI) strongly stabilized this structure and showed preferential binding to a triplex rather than to a duplex. Energy transfer experiments suggest that BePI intercalates within the triple helix. Sequence-specific inhibition of transcription initiation of a specific gene by Escherichia coli RNA polymerase by a triplex-forming oligodeoxynucleotide is strongly enhanced when the triplex is stabilized by BePI. Upon irradiation with ultraviolet light, BePI induces covalent modifications of the target within the triple helix structure. PMID- 1609279 TI - Hydrogen exchange measurement of the free energy of structural and allosteric change in hemoglobin. AB - The inability to localize and measure the free energy of protein structure and structure change severely limits protein structure-function investigations. The local unfolding model for protein hydrogen exchange quantitatively related the free energy of local structural stability with the hydrogen exchange rate of concerted sets of structurally related protons. In tests with a number of modified hemoglobin forms, the loss in structural free energy obtained locally from hydrogen exchange results matches the loss in allosteric free energy measured globally by oxygen-binding and subunit dissociation experiments. PMID- 1609280 TI - Vaccine protection of chimpanzees against challenge with HIV-1-infected peripheral blood mononuclear cells. AB - Because human immunodeficiency virus (HIV) can be transmitted as cell-free virus or as infected cells (cell-associated virus), vaccines must protect against infection by both viral forms. Vaccine-mediated protection of nonhuman primates against low doses of cell-free HIV-1, HIV-2, or simian immunodeficiency virus (SIV) has been demonstrated. It is now shown that multiple immunizations of chimpanzees with HIV-1 antigens protected against infection with cell-associated virus. Protection can persist for extended periods (one animal had not been exposed to viral antigens for 1 year before challenge). These results show that it is possible to elicit long-lasting protective immunity against cell-associated HIV-1. PMID- 1609281 TI - Myoglobin in a cyanobacterium. AB - Myoglobin was found in the nitrogen-fixing cyanobacterium Nostoc commune. This cyanobacterial myoglobin, referred to as cyanoglobin, was shown to be a soluble hemoprotein of 12.5 kilodaltons with an amino acid sequence that is related to that of myoglobins from two lower eukaryotes, the ciliated protozoa Paramecium caudatum and Tetrahymena pyriformis. Cyanoglobin is encoded by the glbN gene, which is positioned between nifU and nifH-two genes essential for nitrogen fixation-in the genome of Nostoc. Cyanoglobin was detected in Nostoc cells only when they were starved for nitrogen and incubated microaerobically. PMID- 1609283 TI - PET images of blood flow changes during anxiety: correction. PMID- 1609282 TI - The motor cortex and the coding of force. AB - The relation of cellular activity in the motor cortex to the direction of two dimensional isometric force was investigated under dynamic conditions in monkeys. A task was designed so that three force variables were dissociated: the force exerted by the subject, the net force, and the change in force. Recordings of neuronal activity in the motor cortex revealed that the activity of single cells was directionally tuned and that this tuning was invariant across different directions of a bias force. Cell activity was not related to the direction of force exerted by the subject, which changed drastically as the bias force changed. In contrast, the direction of net force, the direction of force change, and the visually instructed direction all remained quite invariant and congruent and could be the directional variables, alone or in combination, to which cell activity might relate. PMID- 1609284 TI - ANA position statement on HIV infection and U.S. teenagers. PMID- 1609285 TI - Survey shows widespread public concern about health insurance coverage and costs. PMID- 1609286 TI - Statement of Lucille A. Joel, Ed.D., R.N., F.A.A.N., President ANA in response to April 8th release of Louis Harris Poll on the public's attitudes about health care. PMID- 1609288 TI - Partnership for practitioner of the future. PMID- 1609287 TI - Nurses to be protected against AIDS, hepatitis B under new federal regulations. PMID- 1609289 TI - Breast cancer. PMID- 1609290 TI - Chemoprevention of breast cancer. PMID- 1609291 TI - Local/regional therapy of primary breast cancer: a contemporary multimodal approach. PMID- 1609292 TI - Modified radical mastectomy versus breast conservation: psychosocial considerations. PMID- 1609293 TI - Prognostic value of histopathology in the breast. PMID- 1609294 TI - Treatment of locally advanced breast cancer. AB - It is possible to convert most patients with stage III breast cancer to the state of "no evidence of disease." The challenges now are to increase the cure rate by eradicating local and distant micrometastatic disease, and to minimize the mutilation of locoregional treatment. PMID- 1609295 TI - Hormonal strategies for breast cancer: a new focus on the estrogen receptor as a therapeutic target. PMID- 1609296 TI - The changing role of hormonal therapy in advanced breast cancer. PMID- 1609297 TI - Progress in chemotherapy for metastatic breast cancer. PMID- 1609298 TI - The potential role for biological therapy in the treatment of breast cancer. PMID- 1609299 TI - Asbestos-related chest diseases: plain radiographic findings. AB - In summary, there are a wide range of pulmonary manifestations seen in asbestos exposed individuals from pleural and parenchymal fibrosis to pleural and parenchymal malignancy. The chest roentgenogram has assumed an important role in the detection and surveillance of asbestos-related pleural and parenchymal changes. PMID- 1609300 TI - Recent advances in the early diagnosis of asbestosis. PMID- 1609302 TI - Various aspects of asbestos exposure. PMID- 1609301 TI - Medico-legal issues in occupational lung disease litigation. PMID- 1609303 TI - Case of the season. Lobar atelectasis due to sarcoidosis. PMID- 1609304 TI - Asbestos inhalation and nonmalignant abnormalities of the chest. PMID- 1609305 TI - Asbestos exposures and thoracic neoplasms. PMID- 1609307 TI - How useful are urinary incontinence nursing diagnoses? PMID- 1609306 TI - A practice guideline for urinary incontinence: the challenge to nurses. PMID- 1609308 TI - Managing incontinence through managing the environment. PMID- 1609309 TI - Reimbursement for incontinence products. PMID- 1609310 TI - The ABCs of product selection. PMID- 1609311 TI - Bladder dysfunction after stroke. AB - The effects of stroke are complex and diverse. Deficits experienced depend on the location of damage and vary in severity. Voiding problems resulting from a stroke include uninhibited neurogenic bladder, urgency and frequency, retention, urge incontinence, and overflow incontinence. Because a variety of causative and contributing factors are involved, comprehensive and ongoing evaluation is necessary. Although bladder dysfunction is common initially after stroke, evidence has shown that improvements in voiding occur after the first few weeks. Intermittent sterile catheterization, scheduled voiding, pelvic floor exercises, and relaxation techniques can be effective, especially if other stroke deficit considerations are incorporated into the management plan. PMID- 1609312 TI - Continence management for the frail elderly and cognitively impaired. PMID- 1609313 TI - Effectiveness of vaginal cones in treatment of urinary incontinence. PMID- 1609314 TI - Electrostimulation in the management of voiding dysfunction. PMID- 1609315 TI - Which pad is for you? PMID- 1609316 TI - Implementation of a hospital-based home care continence program. PMID- 1609317 TI - Establishing a nurse continence service in Canada. PMID- 1609318 TI - Promoting continence in Australian nursing homes: a national project. PMID- 1609319 TI - [Medical admission and treatment]. PMID- 1609321 TI - [Clinical manifestations of HIV virus infections]. PMID- 1609320 TI - [Transmission and prevention]. PMID- 1609322 TI - [Biologic diagnosis of HIV infections]. PMID- 1609323 TI - [Nursing care]. PMID- 1609324 TI - [AIDS: another way to conceive of the nursing role]. PMID- 1609325 TI - [The tethered elephant]. PMID- 1609326 TI - [When I go to work, it is always with pleasure]. PMID- 1609328 TI - [The French Agency for the Fight against AIDS]. PMID- 1609327 TI - [The association La Plage: a different view of the hospital]. PMID- 1609329 TI - [Investigations on the needs and problems of persons infected by the HIV virus]. PMID- 1609330 TI - [Contamination by the HIV virus. Care of at risk nursing personnel]. PMID- 1609331 TI - [Dietetics and AIDS: modes of intervention]. PMID- 1609332 TI - [An episode in the life of Louis-Philippe. 3 nursing diagnoses]. PMID- 1609333 TI - [Zero contempt at the hospital]. PMID- 1609334 TI - [General principles of responsibility in 1992: evolution or revolution?]. PMID- 1609335 TI - [AIDS: responses and perspectives]. PMID- 1609336 TI - [AIDS]. PMID- 1609337 TI - Recent advances in antidepressant drugs. AB - Tricyclic antidepressants (TCAs) are notorious for a number of disadvantages, but particularly for an array of side-effects that leads to poor compliance, and also for a dangerous toxicity in overdose. Lofepramine is a new tricyclic that seems safer. Selective serotonin reuptake inhibitors (SSRIs) are more limited in their actions. Side-effects include nausea and insomnia, but on the whole the side effect profile is an improvement on the TCAs. A miscellaneous group of novel antidepressants includes mianserin and trazodone (which both produce drowsiness) and viloxazine (which causes nausea). The reversible inhibitors of monoamine oxidase A (RIMAs) are a group of drugs that, by producing inhibition selectively of monoamine oxidase A (MOA-A), still allow metabolism of tyramine by MAO-B. Moclobemide is a RIMA that has proved itself to be very effective in severe depressive illness. It is remarkably safe and has an exceptionally low incidence of side-effects. It may be expected to be associated with a high acceptability in depressed patients. PMID- 1609338 TI - [Deaconess Institution. Ahead of its time]. PMID- 1609340 TI - [Parliament. More power to the Minister of Health]. PMID- 1609339 TI - [Deaconess Institution. Pioneers with bonnets. Interview by Grethe Kjaergaard]. PMID- 1609341 TI - [Nursing care--thoughts from a hospital bed]. PMID- 1609343 TI - [Our warnings are not taken serious enough. Interview by Peter Skeel Hjorth]. PMID- 1609342 TI - [Nursing care--thoughts from a night-watch ward]. PMID- 1609344 TI - [Deaconess Institution. Tradition and renewal]. PMID- 1609345 TI - [Greenland--no imagination for a no]. PMID- 1609346 TI - [Greenland--expertise costs something]. PMID- 1609347 TI - [Negotiation--new agreement for Greenland]. PMID- 1609348 TI - [Prehospital treatment--a consideration which is insufficient]. PMID- 1609349 TI - [Show significance of defibrillators in emergency ambulances]. PMID- 1609350 TI - [Prehospital treatment--there is very little future adjustment]. PMID- 1609351 TI - [Breast cancer--which operation?]. PMID- 1609353 TI - [Guidelines in ethics]. PMID- 1609352 TI - [Psychological work environment. Heroines, students and stress]. PMID- 1609354 TI - [France--nursing is buried]. PMID- 1609355 TI - [Nursing ethics--a difficult double role. Interview by Kirsten Bjornsson]. PMID- 1609356 TI - Physicians must help write the prescription for health-care reform. PMID- 1609357 TI - Retired physicians face barriers. PMID- 1609358 TI - Group aims to stop lawsuit abuse. PMID- 1609359 TI - State-supplied vaccine would increase vaccination rate. PMID- 1609360 TI - Delegates to debate HIV policy and other controversies. PMID- 1609361 TI - A doctor votes for universal access. PMID- 1609362 TI - Clinic develops HIV education program for deaf, hearing impaired. PMID- 1609363 TI - Several patients have asked me about the effectiveness of condoms in protecting against HIV transmission. How much protection do they provide? PMID- 1609364 TI - Tetanus cases preventable with immunizations. PMID- 1609365 TI - The voice of medicine. Who is listening? PMID- 1609366 TI - Law protects alcohol, drug treatment records. PMID- 1609367 TI - Decision guards pensions from bankruptcy claims. PMID- 1609368 TI - TMA physician leaders study silicone breast implant issue. PMID- 1609369 TI - Controlling breast cancer in older women: the physician's role. AB - The number of women older than 65 years is the highest in history and continues to increase. Given that breast cancer is one of the most common cancers among women and that risk increases with age, it is important that older women participate in regular screening. Physician referral is the reason most women receive a screening mammogram. However, as women's ages and risk increase, the frequency of screening declines, potentially putting older women at greater risk. It is advocated that physicians adopt guidelines for breast cancer screening and practice them with their elderly, as well as younger, patients. PMID- 1609370 TI - Breast cancer in elderly women. PMID- 1609371 TI - Avoiding confusion about the word "narcotic". PMID- 1609372 TI - Role of pneumococcal antigen in the diagnosis of pneumococcal pneumonia. PMID- 1609373 TI - Mediastinal lymph node metastases in lung cancer: is size a valid criterion? PMID- 1609374 TI - Domiciliary ventilation in chronic obstructive lung disease. PMID- 1609375 TI - Pathological assessment of mediastinal lymph nodes in lung cancer: implications for non-invasive mediastinal staging. AB - BACKGROUND: The use of computed tomography in mediastinal staging of lung cancer relies on the premiss that malignant lymph nodes are larger than benign ones. This hypothesis was tested by linking node size and presence or absence of malignancy and looking at factors possibly influencing the size of benign nodes. METHODS: All accessible mediastinal lymph nodes were taken from 56 consecutive patients with lung cancer who underwent thoracotomy. Nodes were measured and histologically examined. Resected cancer bearing lung from 44 of these patients was assessed for degree of acute and chronic inflammation. RESULTS: Lymph node size was not significantly related to the presence of metastatic disease, 58% of malignant and 43% of benign lymph nodes measuring over 15 mm. Similarly, there was no statistically significant relation between size of lymph nodes and the likelihood of malignancy, 20% of lymph nodes of 10 mm or more but also 15% of those less than 10 mm being malignant. Thresholds of 15 and 20 mm showed similar results. The maximum size of benign lymph nodes was significantly greater in those patients with histological evidence of acute pulmonary inflammation than in those without. CONCLUSIONS: The study shows that in patients with lung cancer (1) malignant mediastinal lymph nodes are not larger than benign nodes; (2) small mediastinal lymph nodes are not infrequently malignant; and (3) benign adenopathy is more common in patients with acute pulmonary inflammation. PMID- 1609376 TI - Domiciliary nocturnal nasal intermittent positive pressure ventilation in hypercapnic respiratory failure due to chronic obstructive lung disease: effects on sleep and quality of life. AB - BACKGROUND: Domiciliary assisted ventilation, using negative or positive pressure devices, is an effective treatment for respiratory failure due to chest wall deformity and neuromuscular disease. Negative pressure ventilators have been used with some success in patients with chronic obstructive lung disease in hospital, but attempts to continue treatment at home have been disappointing. This study evaluates the practicalities of nasal intermittent positive pressure ventilation at home in patients with chronic obstructive lung disease and the effect on sleep and quality of life. METHODS AND RESULTS: Twelve patients with chronic obstructive lung disease and hypercapnic respiratory failure received nasal intermittent positive pressure ventilation at home during sleep. At six months eight were continuing with the ventilation. One patient had died and three had withdrawn because they were unable to sleep with the equipment. Full polysomnography performed during ventilation in patients continuing treatment at six months showed an increase in mean PaO2 of 11% (+2% to +23%) and lower mean transcutaneous carbon dioxide tensions (by -2.7 (-1.3 to -5.1) kPa) overnight compared with spontaneous breathing before the start of nasal intermittent positive pressure ventilation. Total sleep time and sleep efficiency changed during ventilation by +72.5 (+21 to +204) minutes and +5% (-3% to +30%) respectively; sleep architecture and the number of arousals were unchanged. Quality of life did not change but was no worse during ventilation. At one year seven patients were still using the ventilator and PaCO2 and bicarbonate ion concentration during the day had improved further by comparison with the values at six months (change from baseline -1.7 (-2.1 to -0.6) kPa, p less than 0.05, and -6.3 (-11.9 to -4) mmol/l, p less than 0.05). CONCLUSIONS: Nasal intermittent positive pressure ventilation can be used effectively at home during sleep in selected patients with chronic obstructive lung disease. Its future place in management can be established only by formal comparison with long term oxygen therapy. PMID- 1609377 TI - Auranofin in the treatment of steroid dependent asthma: a double blind study. AB - BACKGROUND: Long term administration of oral corticosteroids in patients with asthma may be associated with serious side effects. Non-steroidal anti inflammatory drugs, including gold salts, have been shown to reduce the need for systemic corticosteroid treatment in uncontrolled studies. The effect of oral gold (auranofin) on asthma symptoms, lung function, and the need for oral prednisone treatment was investigated. METHODS: A 26 week randomised, double blind, placebo controlled, parallel group trial of auranofin was performed in 32 patients with moderately severe chronic asthma who required an oral corticosteroid dose of at least 5 mg prednisone a day (or equivalent) or 2.5 mg/day prednisone plus more than 800 micrograms/day inhaled corticosteroids. Auranofin was given orally in a dose of 3 mg twice daily. Asthma symptoms, lung function, and adverse effects were assessed at regular intervals. After 12 weeks of treatment prednisone dosage was tapered down by 2.5 mg every two weeks if the patient was clinically stable. Asthma exacerbations were treated with short courses of high doses of oral steroids. RESULTS: Twenty eight of the 32 patients, 13 in the placebo group and 15 in the auranofin group, completed the study. The total corticosteroid reduction achieved after 26 weeks of treatment was significantly greater (4 mg) in the auranofin group than in the placebo group (0.3 mg). The number of exacerbations requiring an increase of steroids was greater in the placebo group (2.1) than in the active group (0.9). A significant increase in FEV1 of 6.4% predicted occurred in the auranofin group during the study and there was a reduction of asthma symptoms such as wheezing and cough. There was no difference between the groups in peak flow measurements or in the number of asthma attacks. The incidence of side effects of auranofin was low, but exacerbations of constitutional eczema were noticeable. CONCLUSION: Auranofin provides an effective adjunct to treatment for steroid dependent asthma, leading to a reduction of oral steroid dose. PMID- 1609378 TI - Assessment of bronchodilatation after spontaneous recovery from a histamine challenge in asthmatic children. AB - BACKGROUND: It would be convenient to be able to measure airway responsiveness to histamine and to bronchodilator drugs on the same day, but whether this can be done reliably is unknown. METHODS: The effect of a prior histamine challenge on the bronchodilator response to salbutamol after spontaneous recovery of FEV1 to 95% of the prechallenge level was studied in two groups of asthmatic children. Fourteen children inhaled 400 micrograms salbutamol after spontaneous recovery from a histamine challenge, followed by a further 100 micrograms salbutamol 20 minutes later. In a second group of eight asthmatic children the study was repeated with 800 micrograms salbutamol, followed by a further 200 micrograms 20 minutes later. RESULTS: After histamine challenge FEV1 returned to baseline in 70 minutes or less on all occasions. The FEV1 20 minutes after 400 micrograms salbutamol was significantly lower after the histamine challenge than on the control day. After the further 100 micrograms salbutamol FEV1 values were similar after the histamine challenge and on the control day. FEV1 values after 800 micrograms salbutamol and the further 200 micrograms dose were not influenced by a prior histamine challenge. CONCLUSIONS: In children with stable asthma in whom FEV1 has returned to baseline after a histamine challenge the FEV1 achieved after 800 micrograms salbutamol is not affected by the histamine challenge. Histamine and bronchodilator responsiveness can thus be assessed reliably on the same day in patients with stable asthma. This has clear advantages for patient care. PMID- 1609379 TI - Effect of dietary sodium on the severity of bronchial asthma. AB - BACKGROUND: A high sodium intake has been found to increase bronchial reactivity in men with asthma. The effects of change in sodium intake on peak flow rate have not been determined. METHODS: The effect of changing dietary salt intake for two weeks on the severity of asthma as measured by peak expiratory flow (PEF) was studied in 17 patients with mild asthma in an open randomised crossover trial. PEF measurements were made by the patients in their own homes. Patients were placed on three levels of dietary sodium intake: normal, low, and high. Sodium intake was assessed by 24 hour urine collection. RESULTS: The mean (SD) urine sodium was 147 (45), 84 (32), and 201 (73) mmol/24 hours in the normal, low, and high sodium intake periods respectively. There were no significant differences in PEF or PEF amplitude (highest--lowest PEF), an index of asthma lability, between the three dietary salt periods. CONCLUSION A low and high dietary salt intake for two weeks has no effect on peak expiratory flow in patients with mild asthma. PMID- 1609380 TI - Dyspnoea assessed by visual analogue scale in patients with chronic obstructive lung disease during progressive and high intensity exercise. AB - BACKGROUND: A study was carried out to determine whether rating of dyspnoea by means of a visual analogue scale during a progressive exercise test is affected by the subject's awareness of the progressive nature of the protocol. METHODS: Nineteen patients with chronic obstructive lung disease (FEV1 mean (SE) 1.06 (0.07) 1) were studied. A preliminary incremental test was carried out with a work rate increasing by 10 watts every minute until the subject could no longer exercise, to determine the maximum work load (Wmax) and to anchor the upper end of the visual analogue scale. This was followed by two exercise tests performed one day apart in randomised sequence, with two different protocols. One was a 12 minute protocol that included two sudden bursts of three minute high intensity exercise, up to the subject's Wmax, each preceded by three minutes of low level exercise. The other test was a conventional three minute incremental test lasting 12 minutes. On both study days the only information given to the subject about the temporal profile of load was that a change would be made every three minutes. The relation between dyspnoea, as assessed by the visual analogue scale, and ventilation, measured during high intensity or progressive exercise, was studied. RESULTS: The mean (SE) rates of increase of dyspnoea with increasing ventilation (% of line length 1(-1) min) obtained by linear regression analysis were similar for the two tests (2.86 (0.20) for progressive exercise and 2.87 (0.25) for high intensity exercise); it was 2.59 (0.25) for the initial burst of high intensity exercise when the data on this were analysed separately. In six subjects with stable disease studied again two months later the reproducibility of the rating of dyspnoea was reasonably good for both protocols. CONCLUSION: The results suggest that in most patients with chronic obstructive lung disease the assessment of exercise induced dyspnoea by means of a visual analogue scale during a progressive exercise test is not affected by the subject's awareness of the progressive increase in work intensity. PMID- 1609381 TI - Pulmonary complications after long term amiodarone treatment. AB - BACKGROUND: Amiodarone hydrochloride is an antiarrhythmic agent useful in arrhythmias refractory to standard therapy. Although interstitial pneumonitis is known to be its most serious side effect, several aspects of amiodarone lung toxicity are still controversial. METHODS: Pulmonary side effects were examined in a sample of 61 symptomless patients (mean (SD) age 55 (7) years) who had had long term treatment with amiodarone (daily maintenance dose 400 mg), selected from 482 men attending the University of Barcelona myocardial infarction project. To allow for the confounding effects of coronary artery disease and tobacco history on lung function, 46 patients who had taken amiodarone for more than one year were matched with a control group from the same population. Subjects underwent measurement of lung volumes, arterial blood gas analysis and an incremental bicycle exercise test. RESULTS: Most lung function values were close to predicted values, though there was a small increase in resting alveolar arterial oxygen tension difference (A-aDO2) at rest (4.8 (1.4) kPa in both groups). There were no differences in the results of forced spirometry or static lung volumes between the two groups, or in the fall in A-aDO2 from rest to exercise. There was a small difference between the amiodarone and the control group in transfer factor for carbon monoxide corrected for lung volume (KCO 1.67 (0.3) and 1.83 (0.3) mmol min-1 kPa-1 l-1 respectively) and in exercise capacity (140 (25) and 120 (30)w). Only three patients showed lung function impairment consistent with pneumonitis. No relation between lung function measures and cumulative doses of amiodarone or desethylamiodarone was found. CONCLUSIONS: The prevalence of clinically evident pulmonary side effects was 4.9%, which is lower than that reported in studies in which higher daily maintenance doses of amiodarone were given. The slightly lower KCO values and lower work load achieved by the patients taking amiodarone suggest a small effect of amiodarone in doses of 400 mg on lung function. A role for individual susceptibility to pulmonary complications of amiodarone treatment is suggested. PMID- 1609382 TI - Mediastinal malignancy: ultrasound guided biopsy through the supraclavicular approach. AB - BACKGROUND: Malignancies located in the upper middle mediastinum usually do not have a sufficiently large acoustic window to permit a conventional ultrasound guided parasternal biopsy. This study was concerned with an alternative approach whereby ultrasound is applied through the supraclavicular paratracheal window to allow percutaneous biopsy of middle mediastinal malignancies. METHODS: Fifteen patients who had upper mediastinal malignancies not in contact with the chest wall underwent real time and Doppler ultrasonographic studies by the supraclavicular approach. None of these tumours could be reached by conventional ultrasound guided parasternal biopsy. The ultrasound was scanned downwards through the supraclavicular fossa, along the acoustic window of the paratracheal soft tissue space. Percutaneous aspiration biopsy was performed with a 22 gauge needle under ultrasound guidance. If fine needle aspiration could not obtain an adequate tissue smear an 18 gauge Trucut biopsy was performed to obtain a histological diagnosis. RESULTS: Twelve of 15 mediastinal malignancies were detected by ultrasound through the supraclavicular approach. These 12 patients underwent percutaneous needle aspiration biopsy under ultrasound guidance. Four of the patients also had a Trucut biopsy because the needle aspirates from the tumours were inadequate. The needle had to pass through the jugular veins in four patients who received fine needle aspiration but in none of the patients who required a Trucut biopsy. Definite histological diagnoses were obtained in all 12 of these patients. Ten of the tumours were malignant and two benign. None of the patients developed any complication. CONCLUSIONS: Ultrasound and ultrasound guided biopsy through the supraclavicular paratracheal window provides a new approach for malignancy located in the upper middle mediastinum, which cannot be reached by conventional ultrasound guided parasternal biopsy. The diagnostic yield of this technique is high and the procedure is relatively safe. PMID- 1609384 TI - Pollution and respiratory morbidity: how much do we accept? PMID- 1609385 TI - Primary leiomyoma of the pulmonary vein. AB - The first case of a primary leiomyoma in a pulmonary vein in an adult is presented. Although rare, leiomyoma and leiomyosarcoma of the lung and great vessels should be included in the differential diagnosis of intrathoracic space occupying lesions. PMID- 1609383 TI - AIDS and the lung: update 1992. 2. Recent developments in the management of the pulmonary complications of HIV disease. PMID- 1609386 TI - Vertebral osteomyelitis presenting with pleuritic chest pain and bilateral pleural effusions. PMID- 1609387 TI - Immune thrombocytopenia complicating pulmonary tuberculosis: case report and investigation of mechanisms. AB - Immune thrombocytopenia and pulmonary tuberculosis presented concurrently in a 20 year old Thai man as a bleeding diathesis. Intravenous immunoglobulin rapidly corrected the thrombocytopenia. Immunofluorescence and immunoblot studies with platelets and mycobacteria showed the presence of platelet surface membrane IgG. PMID- 1609388 TI - Pleural effusion as manifestation of temporal arteritis. AB - Two patients with temporal arteritis who presented with pleural effusion are reported. Both had an exudate that responded to prednisolone treatment. PMID- 1609389 TI - Cystic fibrosis; current survival and population estimates to the year 2000. PMID- 1609390 TI - Prescribed fenoterol and death from asthma in New Zealand, 1981-7: a further case control study. PMID- 1609391 TI - [Diagnostic procedure for lymphadenopathies]. PMID- 1609392 TI - [Lymph node biopsy]. PMID- 1609393 TI - [The clinical case. Dog with generalized lymph node enlargement]. PMID- 1609394 TI - [The clinical case. Horse, swelling in the area of the left mandibular lymph node]. PMID- 1609395 TI - [Necessary provision of newborn lambs with sheep colostrum]. AB - Twenty new-born lambs of each of the breeds Schwarzkopf, Texel and Finnish were fed with 600 ml of pooled colostrum (0-12 h) on the first day of life. The total allocation was fed in portions ranging from 25 to 150 ml at intervals of 1, 2, 3, or 6 hours. The effect of the different intervals and portion volumes on the transintestinal passage of immunoglobulins, the onset of endogenous synthesis, the growth performance of the lambs and the mortality rate was investigated. The concentrations of IgG1, IgG2, IgM and IgA in the sera were analyzed over the course of a nine-week period. 1. The extent of passive immunization by transintestinal passage remained essentially unaffected by different feeding schedules. 2. There was also no effect on the onset of endogenous Ig synthesis. 3. Growth performance and mortality rate likewise showed no discernible differences. PMID- 1609396 TI - [Gonadotropin release and course of diseases after administration of a GnRH analog in cattle with follicular-thecal cysts]. AB - Twenty-five heifers and cows with follicular cysts (high level of total oestrogens, low level of progesterone in plasma) were treated with 20 or 50 micrograms buserelin i.m. 5-84 weeks after parturition. Two hours after medication an increased LH release was observed in all animals. In contrast to LH, FSH concentration was not increased in all cows. Twelve days after treatment a high progesterone concentration in plasma could be determined in 17 of 25 treated animals. Twenty cows showed oestrous symptoms 23.5 +/- 9.6 days after medication. The oestrous cycle was prolonged in 10 cows. Nineteen cows were inseminated and 14 cows became pregnant after 1-4 (phi 1.7 +/- 0.9) inseminations (73.6% of all inseminated cows and 56% of all treated cows). The differences in conception rate and in services per conception after treatment with 20 or 50 micrograms buserelin in favour of the higher dosage cannot be attributed to the medication. PMID- 1609397 TI - [Anesthesia and zootechnical interference in goats]. AB - Some particularities in anesthesia and surgical procedures are discussed. The combination of xylazine with ketamine is recommended for general anesthesia. Particular aspects of the castration of billy goats, deodorization and dehorning are also discussed. PMID- 1609398 TI - [Provision and measures for sanitation in piglet breeding operations with latent swine dysentery]. AB - The eradication and control of swine dysentery in breeding or farrow-to-finish herds require comprehensive knowledge about the epidemiology, pathogenesis and immunology of this typical multifactorial disease. Based upon this background information, the characteristics of chemotherapy, immunoprophylaxis and other necessary concomitant measures are described. The objectives of the eradication and control schemes should be the production of Treponema-free weaner pigs and a long-term prevention of reinfections. PMID- 1609399 TI - [Restraint methods in avian patients. Theoretical basis and practical execution. Part 2]. AB - In avian medicine a correct diagnostic and therapeutic procedure requires restraint. Incidents during restraint result most frequently from the ignorance of certain bird-specific physiological and anatomical characteristics. On the basis of theoretical fundamentals, outlined in part 1, the different restraint techniques are described and demonstrated in detail by figures. PMID- 1609400 TI - [Skin and plumage changes in domestic birds. II. Plumage changes--1]. AB - Modifications of the plumage and specific feather malformations, as developed during the domestication process of different poultry species are described. The modifications include henny feathering, elongated feathers, ear tufts, muffs, and increased numbers of tail feathers. The greater part of these plumage modifications is generally of interest for exhibition poultry fancy. Several of the plumage abnormalities presented distinctly impair the normal species-typical way of life of the animals concerned. The spectrum of negative influences comprises disorders in social behaviour, loss of, or restrictions in typical plumage functions such as weather susceptibility, as well as disabilities of normal mobility. Finally, genetic defects and pathogenic predispositions are also connected with such plumage modifications. PMID- 1609401 TI - [The surgical therapy of equine recurrent uveitis]. AB - Equine recurrent uveitis (ERU) is the most frequently encountered cause of eye problems and blindness in horses. Classic treatment of ERU includes mydriatics, corticosteroids and nonsteroidal anti-inflammatory drugs. Despite vigorous topical and systemic treatment, however, in many cases, the prognosis for preserving vision remains poor. Experiences with surgical treatment of chronic endogenous uveitis in human patients have shown that vision-impairing axial opacities in the vitreous body can be removed by pars plana vitrectomy, and that a considerable decrease in the frequency and severity of uveitic relapses results. So far, 11 eyes of 10 horses were subjected to vitrectomy. All horses had suffered from 3 or more uveitic attacks and had a hazy vitreous. In all cases, at discharge from the clinic, the vitreous chamber was less hazy compared to preoperative findings. At follow-up examinations, 8 eyes (8/10) had normal i.o. pressure, and 2 (2/10) had subnormal i.o. pressure and the vitreous chambers were clear or contained only small floaters. Uveitic attacks had not been observed in the operated eyes. Postoperative complications included fibrinous, or fibrinous-haemorrhagic exudate in the anterior chamber of all eyes, and in one eye, a minor haemorrhage in the vitreous chamber. Our preliminary results indicate that pars plana vitrectomy assuring proper case selection and accurate surgical technique, may contribute to improvement of vision and may delay the progression of uveitic complications in horses. PMID- 1609402 TI - [Radiation exposure of the hands and feet during x-ray studies in small animals]. AB - In early years of radiology, many severe radiation injuries in radiologists were registered. Unfortunately, there are still cases of skin lesions of the hands of veterinarians. The main reason for this is careless handling during the examination. First of all the veterinarian should try to stay out of the primary beam. In addition, he must be aware that lead gloves are no protection against primary rays. In contrast, the risk of placing the feet in the primary beam is relatively low. Monitoring of radiation shows, that, if veterinarians are aware of the hazards, there is no danger of radiation damage. Advice for reducing the exposure dose to the hands is given. PMID- 1609403 TI - [Cytology of the cerebrospinal fluid of dogs and cats with symptoms of meningitis/meningoencephalitis. Part 3]. AB - A review of the literature of cerebrospinal fluid (CSF) cytology of different forms of meningitis/meningoencephalomyelitis in dogs and cats is given. Eight dogs and three cats with signs of meningitis/meningoencephalitis are presented. Four dogs and one cat improved to normal for 1-3 years. The results of CSF cytology of cases whose etiology could not be determined are compared with those of thirteen dogs with distemper. In 8 of 13 sediments eosinophilic inclusions in monocytes and macrophages were found. PMID- 1609404 TI - [Bronchoscopy in small animals]. AB - Indications for bronchoscopy, the equipment and technique performance in dogs and cats are presented. The method is invasive, therefore exact indications such as chronic cough of noncardial origin, foreign bodies, parasitic invasion, paralysis of the larynx or tumours are required. Bronchoscopy enables the surgeon to take samples of bronchial discharge. PMID- 1609405 TI - [Fresh water aquaria and veterinary practice. 2. Studies of proper raising of ornamental fish]. AB - The environmental conditions in 103 fresh-water aquaria were examined and the results compared to the standards as described in part 1 of this publication. The aim was to assess whether the care of aquarium fish was adequate in regard to management and the legal requirements of animal welfare. Disclosed faults are discussed and recommendations for their elimination and avoidance are suggested. PMID- 1609406 TI - [Hemoglobin determination in birds. Comparative studies with wet and dry chemistry (Reflotron)]. AB - The physiological and morphological differences between mammalian and avian blood previously did not allow the determination of avian haemoglobin using dry chemistry systems. It is nevertheless possible to measure Hb values, by means of a special preparation of the blood sample. In this paper the dry chemistry system Reflotron is compared to reference methods. The haemoglobin levels of several bird species are given. Advantages and disadvantages of the different systems are discussed. PMID- 1609407 TI - [Blood collection techniques and normal serum values of important parameters of the Greek land tortoise (Testudo hermanni hermanni)]. AB - The technique and sites of blood sampling in the Herman's tortoise (Testudo hermanni hermanni) are explained. Advantages and disadvantages of each site (Vena coccygealis dorsali, Vena ulnaris) are discussed in comparison to cardiac puncture and clipping a nail. The diagnostic importance of blood examination is shown. Normal values of important blood parameters in clinically healthy animals (n = 17) are given, determined by a dry chemistry system (Kodak Ektachem). PMID- 1609409 TI - Endotoxin or cytokines attenuate ozone-induced DNA synthesis in rat nasal transitional epithelium. AB - Pretreatment of rats with endotoxin (E), a potent inducer of tumor necrosis factor alpha (TNF), and interleukin 1 beta (IL 1), or a combination of TNF and IL1, has been shown to increase levels of lung antioxidant enzymes and protect against pulmonary toxicity associated with hyperoxia. Inhalation of ozone (O3) induces cell injury, followed by increased DNA synthesis, cell proliferation, and secretory cell metaplasia in rat nasal transitional epithelium (NTE). This study was designed to test the effects of E, TNF, and IL1 pretreatment on acute O3 induced NTE cell injury as measured by changes in NTE cell DNA synthesis. Rats were exposed to either 0.8 ppm O3 or air for 6 hr in whole-body inhalation chambers. Immediately before exposure, rats in each group were injected intraperitoneally (ip) with either saline alone or saline containing E (1 microgram/g body wt), TNF (10 micrograms), IL1 (10 micrograms), or both TNF and IL1 (TNF/IL1; 10 micrograms each). Eighteen hours postexposure, rats were injected ip with bromodeoxyuridine (BrdU; 50 micrograms/g body wt) to label cells undergoing DNA synthesis and were euthanized 2 hr later. NTE was processed for light microscopy and immunochemically stained to identify cells that had incorporated BrdU into nuclear DNA. The number of BrdU-labeled NTE nuclei per millimeter of basal lamina was quantitated. There were no significant differences in the number of BrdU-labeled NTE nuclei in air-exposed rats that were injected with E, TNF, IL1, or TNF/IL1 compared with those in saline-injected, air-exposed controls. Rats that were injected with saline and exposed to O3 had approximately 10 times the number of BrdU-labeled NTE nuclei than saline-injected, air-exposed control rats. O3 exposure also induced a significant increase in labeled nuclei in rats that were pretreated with TNF alone. In contrast, pretreatment with E, IL1, or TNF/IL1 attenuated the O3-induced increase in NTE DNA synthesis. These results indicate that both E and the cytokines TNF and IL1 have physiologic effects that can attenuate O3-induced injury or modify the response to NTE cells to O3 exposure. PMID- 1609408 TI - Renal cadmium deposition and injury as a result of accumulation of cadmium metallothionein (CdMT) by the proximal convoluted tubules--A light microscopic autoradiography study with 109CdMT. AB - Chronic, but not acute, exposure to inorganic Cd produces renal damage. However, a single injection of cadmium bound to metallothionein (CdMT) produces renal injury. It is hypothesized that an interorgan redistribution of Cd as CdMT is responsible for the chronic nephrotoxic effect of Cd. To better understand the mechanism(s) of CdMT-induced nephrotoxicity, the intrarenal distribution of 109CdMT was examined. 109CdMT isolated from rat liver was injected into mice at a nonnephrotoxic dose (0.1 mg Cd/kg, iv). The radioactivity in the kidney reached a maximum level (85% of the dose) as early as 30 min following administration and remained essentially constant for up to 7 days after injection. Within the kidney, 109Cd distributed almost entirely to the cortex. Light microscopic autoradiography of the kidney showed that, within the cortex, 109Cd distributed preferentially to the S1 and S2 segments of the proximal convoluted tubules. Within the S1 and S2 segments, the concentration of 109Cd in the basal and apical parts of the cells was similar to that after the nonnephrotoxic dose of CdMT, but after a nephrotoxic dose (0.3 mg Cd/kg) the radioactivity distributed preferentially to the apical portion of the cells. In contrast, light microscopic autoradiography studies with 109CdCl2 revealed that 109Cd was more evenly distributed throughout the proximal tubules. Moreover, after administration of a large dose of inorganic Cd (3 mg Cd/kg), a similar concentration of Cd was found in the convoluted and straight proximal tubules. These data support the hypothesis that CdMT-induced nephrotoxicity might be due, at least in part, to its preferential uptake of CdMT into the S1 and S2 segments of the proximal tubules, the site of Cd-induced nephrotoxicity. PMID- 1609410 TI - Induction of metallothionein by diethyl maleate. AB - Metallothionein (MT) is a sulfhydryl-rich protein whose levels are increased by administration of a variety of agents including metals, cytokines, and oxidative stress agents. Recent studies have suggested that MT is involved in protecting against various forms of oxidative stress, but little is known about the induction of MT by oxidative stress agents. Diethyl maleate (DEM) causes oxidative stress by depleting glutathione levels and is quite effective at increasing hepatic concentrations of MT. The purpose of the current study was to learn more about the relationship between induction of MT and oxidative stress by characterizing this increase in hepatic MT levels produced by DEM. Administration of DEM (3 to 9 mmol/kg, sc) increased hepatic MT concentration in mice as much as 37-fold to 213 micrograms MT/g liver, which is similar to the hepatic MT level seen after administration of other effective MT inducers, such as Cd. The maximal increase of hepatic MT took place 12 to 24 hr after administration of 5 mmol DEM/kg. This rise in MT was preceded by a 60% depletion of hepatic glutathione 3 hr after DEM and increases in both MT-I and MT-II mRNA, which reached a peak 6 to 9 hr after DEM. Administration of DEM (3-5 mmol/kg, sc) also increased MT levels in Sprague-Dawley rats. Pretreatment with DEM protected against Cd-induced hepatotoxicity in a fashion which suggested that a functional MT was being synthesized. In summary, DEM is a highly effective inducer of MT which increases MT at the mRNA level. PMID- 1609411 TI - Bioactivation of chloroform in hepatic microsomes from rodent strains susceptible or resistant to CHCl3 carcinogenicity. AB - The dependence of adduct formation on oxygen concentration and glutathione (GSH) presence was used to characterize the bioactivation of chloroform in hepatic microsomes of Sprague-Dawley and Osborne-Mendel rats and B6C3F1 and C57Bl/6J mice. Both oxidative and reductive pathways were present in all the animals tested. Oxidative activation, very sensitive to oxygen withdrawal, was the major pathway responsible for the covalent binding to microsomal proteins and lipids at 0.1 mM CHCl3. The relative contribution of either pathway to the covalent binding to microsomal lipids at 5 mM CHCl3 was dependent on the oxygen concentration. At 1% pO2, i.e., in the range of the hepatic physiological oxygenation level, B6C3F1 mouse hepatic microsomes showed an oxidative activation distinctly higher than that of hepatic microsomes of other rodents; on the other hand, reductive activation was present only in B6C3F1 mouse and Osborne-Mendel rat liver microsomes. The reductive intermediates were the only contributors to the covalent binding of CHCl3 equivalents to lipids in the presence of GSH; indeed the reactive intermediates produced by the oxidative pathway were fully scavenged by this compound. These results are discussed with respect to the species specificity of CHCl3 hepatocarcinogenesis. PMID- 1609412 TI - Lysosomal storage of sulfated glycosaminoglycans in cultured fibroblasts exposed to immunostimulatory acridine derivatives. AB - The purpose of the present cytological and radiochemical study was to investigate whether the immunomodulatory agent 3,6-bis[2-(diethylamino)ethoxy]acridine (CL 90.100) and three congeners induce lysosomal storage of sulfated glycosaminoglycans (sGAG) in cultured rat corneal fibroblasts. The reason for asking this question was as follows: The four acridine derivatives have molecular similarities with the dicationic amphiphilic compound tilorone, which has previously been shown to cause sGAG storage in cultured cells and in intact rats. The cells were exposed to the drugs for 72 hr. Tilorone served as reference. All acridine derivatives caused cytological alterations which, on the basis of the cytochemical results, were indicative of lysosomal sGAG storage. The threshold concentrations ranged from 0.3 to 0.7 microM. Radiochemical experiments showed that CL-90.100 up to 10 microM induced [35S]GAG storage in a dose-dependent manner, with an EC50 of 2 microM. Concentrations above 10 microM were cytotoxic. Experiments with equimolar concentrations (3 microM) demonstrated that three of the acridine derivatives were more potent and one was less potent than tilorone. Additionally, CL-90.100 was tested on bovine corneal fibroblasts, with cytochemical and radiochemical results similar to those in rat cells. The present findings show that (a) the four acridine derivatives induce lysosomal sGAG storage; (b) the acridine ring, compared with the fenfluorenone ring (tilorone), enhances this potency; and (c) the substituents at the nitrogens can have some influence on the potency to induce sGAG storage. PMID- 1609413 TI - Induction of mucopolysaccharidosis in rats by treatment with immunostimulatory acridine derivatives. AB - In the accompanying paper, four dibasic acridine derivatives were reported to induce lysosomal storage of sulfated glycosaminoglycans (sGAG), i.e., mucopolysaccharidosis, in cultured fibroblast (Handrock et al. Toxicol. Appl. Pharmacol. 114, 1992). The purpose of the present morphological and biochemical investigation was to examine whether two representatives of the acridine derivatives, namely 3,6-bis[2-(diethylamino)ethoxy]-acridine and the piperidino analogue, induce mucopolysaccharidosis in intact organisms. Rats were orally treated with 60-80 mg/kg up to 22 weeks. Morphological examination of liver, spleen, and blood lymphocytes yielded cytochemical evidence of mucopolysaccharidosis. Biochemically, up to a 48-fold increase of the urinary excretion of sGAG was found. In the liver and spleen of chronically treated rats, the sGAG contents were elevated by factors up to 56 and 23, respectively. Heparan sulfate and dermatan sulfate contributed most to the total increase of sGAG; chondroitin sulfate was stored to a minor degree. For one compound, the tissue concentrations were determined. It was found that the drug was accumulated in the tissues. Due to their fluorescent properties, the drugs could be detected by fluorescence microscopy to be present in high concentrations within the sGAG storing lysosomes. On the basis of these observations and of the biochemical data it appears justified to assume a ratio of at least one drug molecule per disaccharide unit of the sGAG to be present in the lysosomes. It is proposed that this leads to the formation of sGAG-drug complexes in the lysosomes. Such complexes may be indigestible substrates for the lysosomal enzymes, thus leading to mucopolysaccharidosis. For toxicologic practice, the cytochemical examination of lymphocytes is recommended as a simple measure for early detection and monitoring of this adverse drug effect. PMID- 1609414 TI - Use of the fungicide carbendazim as a model compound to determine the impact of acute chemical exposure during oocyte maturation and fertilization on pregnancy outcome in the hamster. AB - Early pregnancy loss due to acute chemical exposure is difficult to detect and essentially impossible to characterize in humans. Here we use a hamster animal model to identify early pregnancy loss due to an acute chemical exposure to the female during the perifertilization interval. The fungicide carbendazim (methyl 1H-benzimidazole-2-carbamate), a microtubule poison with antimitotic activity, was selected as a model compound because it would be expected to perturb microtubule-dependent events occurring in the oocyte during meiotic maturation and fertilization. Such effects would likely lead to aneuploidy in the zygote with subsequent early pregnancy loss. Female hamsters were given a single oral dose of carbendazim during meiosis I (the afternoon of proestrus) prior to breeding, or during meiosis II (the morning of estrus) following overnight breeding. Pregnancy outcome was assessed on Day 15 (the afternoon before parturition). When given during during meiosis I, carbendazim treatment (750 or 1000 mg/kg body weight) significantly reduced the percentage of pregnant hamsters. In those animals that became pregnant, the average number of live pups was significantly lower at all dosages of carbendazim used (250, 500, 750, and 1000 mg/kg), an effect attributable to both preimplantation and early postimplantation losses. When given early on the morning of estrus, shortly before and during fertilization (0500 or 0600 hr), carbendazim treatment (1000 mg/kg) produced a similar decrease in litter size. This effect disappeared when carbendazim was administered at a slightly later time (0800 or 0900 hr), after the microtubule-dependent events of fertilization have occurred. These results demonstrate that a single exposure to a microtubule poison such as carbendazim at critical times, coincident with microtubule-dependent meiotic events, can result in very early pregnancy loss. Such loss was readily measurable in this animal model and serves as the basis for further mechanistic studies which would be impossible to conduct in humans. PMID- 1609415 TI - Effect of exposure concentration on the disposition of inhaled butoxyethanol by F344 rats. AB - The glycol ethers are a class of solvents widely used due to their range of vapor pressures and miscibility in aqueous and organic media. Butoxyethanol (BE) causes anemia and lowered hematocrits in rats due to direct hemolysis of red blood cells. Exposure to BE is most likely to occur by dermal contact or by inhalation. In this paper, we report the uptake, metabolism, and excretion of BE following 6 hr exposure at different inhaled concentrations. The uptake and metabolism of BE were essentially linear up to 438 ppm. The majority of the inhaled butoxy [14C]ethanol was eliminated in the urine with butoxyacetic acid (BAA) being the major urinary metabolite, accompanied by lesser amounts of ethylene glycol and BE glucuronide. A small proportion (5-8%) of the retained BE was exhaled as 14CO2. Most (greater than 80%) of the [14C]BE-derived material in blood was in the plasma. BAA was the major metabolite of BE in plasma. Ratios of ethylene glycol to BAA in plasma were higher than those in urine. The BE-derived 14C in plasma rapidly became associated with the acid-precipitable (protein) fraction, probably due to binding of metabolites to proteins or incorporation of the BE metabolites into the carbon pool. These results indicate that, in rats, overall metabolism of BE to BAA, the hemolytic metabolite, was linearly related to the exposure concentration up to a concentration that caused severe toxicity (438 ppm). Assuming that the toxicity of inhaled BE is directly proportional to the formation of BAA, the toxicity of inhaled BE can be expected to be linearly related to the exposure concentration up to exposure concentrations that cause mortality. PMID- 1609416 TI - A multivariate study of protective effects of Zn and Cu against nephrotoxicity induced by cadmium metallothionein in rats. AB - Factorial experimental design was used to study the protective effects of Zn and Cu on cadmium-metallothionein(CdMT)-induced nephrotoxicity in male Wistar rats. In the factorial design two levels of Zn (0 and 25 mg/kg body weight), two levels of Cu (0 and 12.5 mg/kg), and two levels of CdMT (0.1 and 0.4 mg of Cd/kg) were used as varied factors. The factorial design was complemented with a center point with all three variables at an intermediate setting, i.e., Zn at 12.5 mg/kg, Cu at 6.25 mg/kg, and CdMT at 0.25 mg Cd/kg. Each of the nine combinations of settings was administered to one of nine groups with six rats in each. Zn and Cu were injected sc 24 hr prior to the injection of CdMT. The concentrations of protein and Ca in urine and Ca in renal cortex were used as effects. The relationship between the experimental design settings and the effects were modeled with multiple regression. The multiple regression analysis revealed that for the high dose of CdMT (i) the enhanced values of protein in urine caused by CdMT injection could be more efficiently reduced by Zn than by Cu, and (ii) excessive Ca in urine and renal cortex could be more efficiently reduced by Cu than by Zn. No significant synergism or antagonism between Cu and Zn was found. These models can be used to estimate the dose levels of Zn and Cu which will reduce the toxic effects of CdMT. The treatment of 20.4 mg/kg Zn, for example, will reduce the effects of 0.4 mg Cd/kg as CdMT on protein in urine, and 2.8 mg/kg Cu will reduce the Ca in urine to the levels of those caused by 0.25 mg Cd/kg (no Zn and Cu). Similarly, the effect of 0.4 mg Cd/kg on Ca level in renal cortex can be reduced to that of 0.28 mg Cd/kg as CdMT by 7.98 mg Cu/kg, which is three times as efficient as Zn. The obtained results might be of importance in understanding the mechanism of cadmium toxicity and the potential risk to the health of the population exposed to cadmium occupationally or environmentally. PMID- 1609417 TI - A physiologically based pharmacokinetic and pharmacodynamic model to describe the oral dosing of rats with ethyl acrylate and its implications for risk assessment. AB - A physiologically based pharmacokinetic and pharmacodynamic model has been developed to describe the absorption, distribution, and metabolism of orally dosed ethyl acrylate. The model describes the metabolism of ethyl acrylate in 14 tissues based on in vitro metabolic studies conducted with tissue homogenates. The routes of metabolism included in the model are carboxylesterase-catalyzed ester hydrolysis, conjugation with glutathione, and binding to protein. To adequately describe the rate and extent of glutathione depletion following gavage dosing, the steady-state rate of glutathione synthesis in the organs of interest was included. In vivo validation of the model was conducted by comparing the predictions of the model to the results of a variety of gavage dosing experiments with ethyl acrylate, including (1) the time course of glutathione depletion in a variety of tissues up to 98 hr following dosing at three dose levels, (2) the rate and extent of radiolabeled carbon dioxide excretion, and (3) protein binding in the forestomach. The very rapid metabolism predicted by the model was consistent with the observation that ethyl acrylate was metabolized too rapidly in vivo to be detected by common analytical techniques for tissue metabolite analysis. The validation data indicated that the model provides a reasonable description of the pharmacokinetics and the pharmacodynamic response of specific rat tissues following gavage dosing of ethyl acrylate. A dose surrogate, or measure of delivered dose, for ethyl acrylate was calculated and correlated with the incidence and severity of contact site toxicity (edema, inflammation, ulceration, and hyperplasia). The model provides a quantitative tool for evaluating exposure scenarios for their potential to induce contact-site toxicity, and it provides a quantitative approach for understanding the lack of toxicity in tissues remote from the dosing site. PMID- 1609418 TI - Comparison of three tetramic acids and their ability to alter membrane function in cultured skeletal muscle cells and sarcoplasmic reticulum vesicles. AB - Cyclopiazonic acid is a potent inhibitor of calcium uptake and Ca(2+)-ATPase activity in sarcoplasmic and endoplasmic reticulum. In L6 muscle myoblasts, cyclopiazonic acid stimulates the uptake of tetraphenylphosphonium, a lipophilic membrane potential probe, and has antioxidant properties. The purpose of the present study was to investigate the structural requirements necessary for causing the surface charge alterations, and the antioxidant activity in L6 skeletal muscle myoblasts, and for inhibition of calcium transport by rat skeletal muscle sarcoplasmic reticulum vesicles. This was accomplished by comparing the effects of two structurally related tetramic acids, cyclopiazonic acid imine and tenuazonic acid, with cyclopiazonic acid. Cyclopiazonic acid imine inhibited oxalate-assisted 45Ca2+ uptake and ATPase activity in sarcoplasmic reticulum vesicles and stimulated tetraphenylphosphonium accumulation by L6 muscle myoblasts. However, these effects required an approximately fourfold higher concentration than that of cyclopiazonic acid. Tenuazonic acid, up to 1 mM, had no effect on oxalate-assisted 45Ca2+ uptake or Ca(2+)-ATPase activity in sarcoplasmic reticulum vesicles and did not stimulate tetraphenylphosphonium accumulation by L6 muscle myoblasts. Cyclopiazonic acid was only slightly more effective than cyclopiazonic acid imine at preventing the patulin-induced increase in thiobarbituric acid positive substance (used to estimate lipid peroxidation); tenuazonic acid was totally ineffective. Previously, it was shown that cyclopiazonic acid was twice as effective as cyclopiazonic acid imine at preventing increases in thiobarbituric acid positive substance in cultured renal cells, LLC-PK1. Thus, the indole nucleus of cyclopiazonic acid is essential for the membrane-associated biological activity; however, modification of the acetyl group reduces the potency of the activity. PMID- 1609420 TI - Metabolism of [14C]benzene by cynomolgus monkeys and chimpanzees. AB - Rodent bioassays indicate that B6C3F1 mice are more sensitive to the carcinogenicity of benzene than are rats. The urinary profile of benzene metabolites is different in rats vs mice. Mice produce higher proportions of hydroquinone conjugates and muconic acid, indicators of metabolism via pathways leading to putative toxic metabolites, than do rats. In both species, metabolism to hydroquinone and muconic acid is favored at low concentrations of benzene, indicating that these pathways are easily saturated. These species differences in the metabolism of benzene make it difficult to predict the health risk to humans and how this risk varies with dose. For this reason, the metabolism of [14C]benzene by cynomolgus monkeys and chimpanzees, animals phylogenetically closer to humans than rodents, was studied. Monkeys were dosed ip with 5, 50, or 500 mg [14C]benzene/kg body wt. Urine was collected for up to 24 hr following exposure and was analyzed for benzene metabolites. The proportion of the administered 14C excreted in the urine of monkeys decreased from approximately 50 to 15% as the dose increased. Phenyl sulfate was the major urinary metabolite. The proportion of hydroquinone conjugates and muconic acid in the monkey's urine decreased as the dose increased. The proportion of catechol conjugates was not affected by dose. The proportion of these metabolites in the urine was quite variable from animal to animal, but the proportion of muconic acid was consistently much lower in the monkey than in the mouse or rat. Three chimpanzees were administered 1 mg [14C]benzene/kg body wt, iv; essentially all of the injected 14C was recovered in the urine. Of the total urinary metabolites, 79% were accounted for by phenyl conjugates and less than 15% by hydroquinone conjugates or muconic acid. Catechol conjugates were not detected. The metabolism of benzene appeared to be qualitatively similar but quantitatively different in the species studied. The mouse, the sensitive rodent species, forms the highest levels of hydroquinone conjugates and muconic acid and the chimpanzee, the lowest. In all animal species studied for the effect of dose on benzene metabolism, as the dose decreased, a larger proportion of the benzene metabolites was represented by hydroquinone conjugates and muconic acid. PMID- 1609419 TI - Acute ozone-induced lung injury in neutrophil-depleted rats. AB - To test the hypothesis that neutrophils contribute to acute, ozone-induced epithelial damage in the lung, rats were depleted of their circulating neutrophils by intraperitoneal injection of a rabbit anti-rat neutrophil serum (ANS) 12 hr prior to an 8-hr exposure to 1.0 ppm ozone. Additional rats were given an injection of normal rabbit serum (NRS) prior to ozone exposure. Exposures were followed by postexposure periods in filtered air for 0, 4, or 16 hr. Control rats were given either ANS or NRS and then exposed only to filtered air. Analysis of bronchoalveolar lavage fluid (BALF) from NRS-treated rats revealed a significant increase in total neutrophils above that of controls at the 4- and 16-hr postexposure times, with a peak increase at 4 hr postexposure. In contrast, there was almost total ablation of the BALF neutrophil response in the ANS-treated rats at all times. Ozone caused an increase in BALF protein, fibronectin, and interleukin-6 above those in controls in both the NRS- and ANS treated rats, but the only significant difference between the two groups was a level of fibronectin in the neutrophil-depleted animals higher than that in the neutrophil-sufficient animals at the 0-hr postexposure time. Electron microscopic morphometry on lungs fixed by intravascular perfusion demonstrated no significant differences in the volume per surface area epithelial basal lamina (Vs) of necrotic and degenerating epithelial cells in central acini between the neutrophil-depleted and neutrophil-sufficient animals. From these results, we concluded that neutrophils do not play a detectable role in contributing to the early epithelial damage in the lung caused by an acute exposure to ozone. PMID- 1609421 TI - Direct and indirect actions of HgCl2 and methyl mercury chloride on permeability and chloride secretion across the rat colonic mucosa. AB - The actions of two mercury compounds, the inorganic HgCl2 and the organic methyl mercury chloride (MeHg), and of CdCl2 on ion transport across the rat colon were studied with the Ussing chamber and the everted sac method. The mercury compounds (5-50 microM), but not CdCl2, administered to the luminal side, induced a large, concentration-dependent increase of tissue conductance (Gt). The transepithelial movement of the extracellular marker, mannitol, was enhanced in the presence of the mercury compounds, indicating that they cause an increase in the permeability of the epithelium. Morphological studies revealed that at least for HgCl2 this increase of the permeability was associated with a loosening of the tight junctions, severe alterations of the enterocytes, and a loss of the continuity of the epithelium. After washing out HgCl2, cells neighboring the altered enterocytes developed lateral processes and in this way restored the continuity of the epithelial layer. In parallel, the mercury compounds induced an increase of short-circuit current (Isc), which is indicative of an induction of Cl- secretion. The increase of Isc, but not that of Gt, was suppressed by indomethacin and, in the case of MeHg, also by tetrodotoxin. These results suggest that MeHg and HgCl2 induce Cl- secretion by an indirect effect on the epithelium, which is mediated by prostaglandins. PMID- 1609422 TI - Chloride secretion induced by mercury and cadmium: action sites and mechanisms. AB - The actions of two mercury compounds, HgCl2 and methyl mercury chloride (MeHg), and of CdCl2 on the epithelium of the rat colon were studied with the whole-cell patch-clamp technique and the Ussing chamber. MeHg (50 microM) induced an increase of membrane outward current (I(out)) in enterocytes of isolated crypts patched from the basolateral side. This action was inhibited by a Cl- channel blocker and a K+ channel blocker, indicating an increase of both the Cl- and the K+ conductance. In contrast, HgCl2 (50 microM) did not affect I(out), whereas CdCl2 (50 microM) decreased it slightly. In mucosal preparations all three compounds induced a concentration-dependent increase in short-circuit current (Isc) when administered to the serosal, i.e., contraluminal side. Sensitivity to chloride transport blockers and anion replacement experiments revealed that the increase in Isc represented Cl- secretion. In contrast to the actions of luminally applied mercury compounds, the increase of tissue conductance (Gt) was only small. Tetrodotoxin and indomethacin suppressed the effect of the metal compounds on Isc and Gt, while atropine diminished it only partly. This indicates that the secretory action of these heavy metals has not only a direct effect on epithelial cells but is also mediated by prostaglandins and cholinergic and noncholinergic neurons. PMID- 1609423 TI - Distribution and disposition associated with compartmentation of body fluid in the developing fetus of the rat. AB - The relationship between the developmental change of the disposition kinetic character for p-phenylbenzoic acid (PPBA) and compartmentalized fluid of the body was investigated in the rat fetus. [14C]Inulin injected into the umbilical vein attained the steady state distribution at 8 min on Day 17 of gestation and at 10 min on Day 21 of gestation. Inulin space (Vi) on Day 17 of gestation was 0.686 ml/g body wt and decreased to 0.542 ml/g on Day 21 of gestation. [14C]Inulin injected into the fetuses on Days 18 and 21 of gestation remained in the fetal body. Hence a determination method of the apparent volume of distribution (Vd) for PPBA was developed using Vi. Vd on Day 17 of gestation was 0.640 ml/g body wt and decreased to 0.454 ml/g on Day 21 of gestation. Body water based on wet body weight showed no significant change. The analysis of PPBA distribution by the compartmentalization of body fluid suggests that the developmental change of Vd is reflected by that of Vi. The elimination rate (K(el)) from the fetus decreased rapidly in the earlier stages of gestation and slowly in the later stages of gestation. The change of the transplacental clearance (Cl) was mainly reflected by that of K(el) throughout the gestation period. However, the change of Vd partly influenced the change of Cl in the later stage of gestation. PMID- 1609424 TI - The specificity of carboxylesterase protection against the toxicity of organophosphorus compounds. AB - The ability of endogenous carboxylesterase (CaE) to protect against the lethal effects of a variety of organophosphorus (OP) compounds was examined in rats. The in vivo protection provided by endogenous CaE was measured by the difference in the LD50 values of OP compounds in control rats and rats whose CaE activity had been inhibited by sc injection with 2 mg/kg of 2-(O-cresyl)-4H-1,3,2 benzodioxaphosphorin-2-oxide. Endogenous CaE provided significant protection against the in vivo toxicity of soman, sarin, tabun, and paraoxon, but not against dichlorvos, diisopropyl fluorophosphate, or ethoxymethyl-S-[2 (diisopropylamino)ethyl] thiophosphonate (VX). The relationship between the in vivo CaE protection against OP compounds and their relative reactivities with CaE and acetylcholinesterase (AChE) was evaluated by measuring the in vitro bimolecular rate constants (ki) for inhibition of plasma CaE and brain AChE. Except for VX, ki values for CaE inhibition varied less than 10-fold while ki values for AChE inhibition varied 10(5)-fold. The degree of in vivo inhibition of CaE by equitoxic doses of the OP compounds increased as the CaE/AChE ki ratio increased. However, the protective ratio of the LD50 values in control vs CaE inhibited rats decreased as the CaE/AChE ki ratio increased. This inverse relationship between in vivo CaE protection and relative in vitro reactivity for CaE suggested that CaE detoxication is more important for highly toxic OP compounds (i.e., compounds with high AChE ki values and low LD50 values) than for less toxic compounds. PMID- 1609425 TI - Cytochrome P-450- and glutathione-associated enzyme activities in freshly isolated enriched lung cell fractions from beta-naphthoflavone-treated male F344 rats. AB - Xenobiotics metabolized in rat pulmonary tissue are often selectively cytotoxic to individual lung cell populations. A non-homogeneous distribution of xenobiotic biotransformation enzymes, e.g., cytochrome P-450 (P-450)- and glutathione (GSH) associated enzymes, in rat lung tissue may underlie this observed cell-selective pneumotoxicity. To evaluate this hypothesis, the relative activities of P-450- and GSH-associated enzymes were measured in sonicated, freshly isolated preparations containing enriched complements of individual toxicant-sensitive lung cell types, including non-ciliated bronchiolar epithelial (Clara) cells (24% pure), alveolar type II cells (86% pure) and pulmonary endothelial cells (identified by membrane-associated angiotensin converting enzyme activity). Lung cell fractions were isolated by centrifugal elutriation from male F344 rats that 48 h earlier received a single i.p. injection of either P-450-inducer beta naphthoflavone (50 mg beta-NF/kg body weight) or corn oil vehicle. The enriched Clara cell fraction possessed (per 10(6) cells) greater P-450 and reduced GSH contents and higher enzyme activities (i.e., NADPH- and NADH cytochrome c reductases, benzyloxy (BROD)-, pentoxy (PROD)- and etoxyresorufin (EROD)-O dealkylases, GSH transferase, GSH peroxidase, GSH reductase and NADPH quinone oxidoreductase) than either the enriched type II cell or endothelial cell preparations. However, the relative biochemical activities for the enriched fractions (Clara greater than type II greater than endothelial) generally reflected respective sonicate cellular protein content. Treatment of rats with beta-NF resulted in: (a) an induction in EROD activity in the enriched preparations of type II cells, Clara cells and endothelial cells (125-, 89- and 35-fold, respectively); (b) higher NADPH quinone oxidoreductase activities, which were increased to the greatest degree (3-fold) in the enriched type II cell fraction and (c) a small elevation in GSH transferase activity measured in the enriched Clara cell fraction. Although the enriched rat lung cell preparations possessed unique biochemical profiles for constitutive and beta-NF-inducible P 450- and GSH-associated enzymes, additional studies with higher purity preparations (e.g., Clara cells) will be required to more fully evaluate the relationship between relative cellular complements of xenobiotic biotransformation enzymes and pneumotoxicant susceptibility. PMID- 1609426 TI - Ranking toxicity of industrial dusts by bronchoalveolar lavage fluid analysis. AB - Female wistar rats were inoculated intratracheally with 10 mg/ml suspensions of various dusts, viz: quartz, fly ash, mica and corundum in physiological saline. Biochemical markers of bronchoalveolar lavage fluid (BALF) were analysed 8 days after the instillation of the dusts. Elevated levels of proteins, sialic acid and phospholipid contents and the activity of lactate dehydrogenase correlated well with the degree of the known fibrogenic potential of different dusts in the lungs in the following order, quartz greater than fly ash greater than mica greater than corundum. beta-glucuronidase activity, was however, only elevated in the quartz inoculated group of rats. It is suggested that biochemical constituents of BALF analysed shortly after the exposure to different dusts can be useful to mirror alterations in the tissue response to mineral dusts. PMID- 1609427 TI - Blood lactate and catecholamine levels in the carbon monoxide-exposed rat: the response to elevated glucose. AB - Previous studies have shown that elevated blood glucose is detrimental to the outcome in acute carbon monoxide (CO) poisoning. The present goals were to characterize the blood lactate and catecholamine changes and to determine whether elevated blood glucose results in increases in the levels of these substances. Two groups of adult Sprague-Dawley, Levine-prepared, female rats (n = 22 each) were exposed to 2400 ppm CO for 90 min: one group received nothing (CO alone), while the other group was infused with a 50% glucose solution (4 ml/kg) (CO + glucose). The usual hypothermia, hypotension, bradycardia and hemoconcentration associated with acute severe CO poisoning were observed. Survival rates were 68% and 54% in the CO alone and CO + glucose groups, respectively. Arterial blood pressure tended to decline more in rats that died; the difference was significant in the CO + glucose group. In the CO alone group, plasma glucose concentration was significantly lower after CO exposure in rats that died than in survivors (35 +/- 15 vs. 99 +/- 16 mg/dl). In the CO + glucose group, glucose concentration was significantly higher after 45 min in rats that died (d) than in survivors (s) (447 +/- 29 vs. 324 +/- 31 mg/dl). Elevated blood glucose in the CO + glucose group failed to significantly increase blood lactate; however, lactate tended to be higher in rats that died in both groups [CO alone group: 175 +/- 17 (d) vs. 138 +/- 9 (s); CO + glucose group: 154 +/- 10 (d) vs. 143 +/- 8 (s)]. Plasma epinephrine and norepinephrine increased significantly 6-10-fold and 2-6-fold in each of the two groups, respectively; however, catecholamine levels were not related to either the administration of glucose or survival. With regard to CO poisoning in this animal model, the results do not support the hypotheses that elevated blood glucose exacerbates the increase in blood lactate, that increased catecholamine increases glucose, or that greater CO-induced hypoglycemia results from increased lactate production. The results do show that death is related to abnormally high or low blood glucose, but that it is not due to higher blood lactate or catecholamine levels. PMID- 1609428 TI - Protective effect of diosmetin on in vitro cell membrane damage and oxidative stress in cultured rat hepatocytes. AB - Primary cultures of rat hepatocytes were used to study the effects of the flavonoids diosmin and its main metabolite diosmetin on the cell membrane damage caused by erythromycin estolate (EE) and oxidative stress caused by tert butylhydroperoxide (TBHP). The damage was evaluated by the leakage of intracellular enzymes lactate dehydrogenase, aspartate-aminotransferase and the residual cell content of a lysosomal marker acid phosphatase (AP). After treating the cells for 40 h with diosmetin EE induced less enzyme leakage. The content of AP was kept higher by diosmetin pretreatment after 6 h exposure to EE. Diosmin at the same concentrations had barely any effect. Diosmetin, but not diosmin, also protected against TBHP toxicity and this was related to lower lipid peroxidation and higher glutathione content caused by pretreatment with the flavonoid. When the cells were treated simultaneously with TBHP and diosmetin after 21 h of culture, the protection by the flavonoid was even higher. In fact the antioxidant activity of diosmetin was considerably greater than that of diosmin. After 40 h exposure to both flavonoids diosmin but not diosmetin was detectable in the cell membrane fraction, suggesting that the latter's protective effect is associated with its metabolites. PMID- 1609429 TI - Toxicity assessment of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) in primary skin and liver cell cultures. AB - The present study was undertaken to assess and compare the in vitro cytotoxicity of toxins T-514 and T-544 of buckthorn (Karwinskia humboldtiana) using primary cultures of rat hepatocytes and keratinocytes. Cell cultures were exposed to 6, 12, 25 and 50 microM toxins for 2-, 4-, 6- and 24-h periods. Cytotoxicity was determined by release of the cytoplasmic enzyme, lactate dehydrogenase (LDH), in culture media, methylthiazoltetrazolium (MTT) reduction and neutral red (NR) uptake. An increase in LDH leakage was observed in liver cell cultures as early as 2 h with 50 microM T-544 and with 6 microM T-514 and T-544 at 6 h and 24 h, respectively. In the NR assay the toxicity was evident at 2 h with 12 microM T 514 and T-544 and with 6 microM concentrations of both toxins at 6 h. On the other hand, a decrease in MTT reduction was detected at 4 h with 50 microM concentrations of both toxins and with 25 microM T-544 and 12 microM T-514 at 6 h and 6 microM T-514 and T-544 at 24 h. Both toxins were shown to be highly hepatotoxic; T-514 was more toxic than T-544. In the skin cell cultures, the toxicity of the toxins was not as severe and was not expressed until 12 h of exposure. PMID- 1609430 TI - Fluoranthene induces programmed cell death and alters growth of immature B cell populations in bone marrow cultures. AB - Many studies have demonstrated that polycyclic aromatic hydrocarbons adversely affect mature mammalian immune systems. However, little is known about the cellular mechanism(s) mediating this immunosuppression or the potential for these ubiquitous environmental chemicals to similarly compromise lymphocyte development (lymphopoiesis). Murine bone marrow cultures were exploited in the present studies to evaluate the potential for fluoranthene, a mutagenic, cocarcinogenic, polycyclic aromatic hydrocarbon, to modulate B cell lymphopoiesis. In this well characterized system, interactions between immature bone marrow-derived precursor B (preB) cells and bone marrow-derived stromal cells closely mimic preB-stromal cell interactions in vivo and resemble interactions between other bone marrow derived hematopoietic cells and their supporting stroma. Data presented herein indicate that: (i) fluoranthene suppresses B lymphopoiesis within 2 days in bone marrow cultures; (ii) fluoranthene suppresses lymphopoiesis at least in part by direct interactions with preB cells; (iii) fluoranthene lymphotoxicity is mediated by rapid induction of DNA fragmentation characteristic of programmed cell death (apoptosis) and (iv) preB cell populations surviving the initial death signal or preB cell populations exposed to lower doses of fluoranthene (0.5-5 micrograms/ml) exhibit altered growth and survival characteristics. The data suggest several levels at which fluoranthene could compromise B lymphopoiesis. PMID- 1609431 TI - Inhibitory effect of lead on the release of tissue plasminogen activator from human vascular endothelial cells in culture. AB - To evaluate the toxicity of lead on the blood fibrinolytic system, vascular endothelial cells from human umbilical vein were cultured in the presence of lead and the content of tissue plasminogen activator antigen (t-PA:Ag) released into the medium was determined by enzyme immunoassay. It was found that lead significantly decreased the t-PA:Ag release from the cells. Although heavy metals including cadmium, mercury, cobalt, manganese, nickel, zinc and copper as well as lead each had an inhibitory effect, lead was the potent inhibitor. Lead significantly disturbed thrombin up-regulation of t-PA:Ag release and significantly amplified endothelin-1 down-regulation of it. Incorporation of [3H]thymidine into the acid-insoluble fraction of the cell layer was significantly increased by lead; however, that of [14C]leucine was unchanged by the metal. In lead-treated cells, a significant accumulation of lead was observed but calcium content was increased slightly. From these results, it was suggested that lead decreased the release of t-PA:Ag from cultured endothelial cells without nonspecific inhibition of protein synthesis; lead may stimulate the calcium-dependent down-regulation of endothelial cell t-PA:Ag release by calcium or by mimicking calcium. PMID- 1609432 TI - Depletion of essential elements by calcium disodium EDTA treatment in the dog. AB - The effect(s) of calcium disodium ethylenediaminetetraacetate (CaNa2EDTA) on the metabolism of Zn, Cu and Mn was investigated in mongrel female dogs. Dogs received either CaNa2EDTA (0.75 mmol/kg subcutaneously) or 0.9% NaCl (controls). Urine was collected every 6 h. Tissue samples were obtained from liver, kidney, duodenum, muscle, hair, skin and bone post exsanguination. CaNa2EDTA treatment increased urinary excretion of Zn, Cu and Mn, significantly when compared to controls (P less than 0.05, n = 5). Furthermore, CaNa2EDTA either decreased Zn levels (hair, duodenum, skin) and Mn levels (hair) or increased Cu levels in kidneys (P less than 0.05). These data suggest that the sustained urinary loss of Zn, Cu and Mn was probably associated, in part, with mobilization and redistribution of these essential elements from storage tissues as well as soft tissues. It was concluded that the use of calcium disodium EDTA for the management of heavy metal poisoning in dogs could adversely affect the metabolism of essential elements, particularly Zn, Cu and Mn. PMID- 1609433 TI - Teratogenic evaluation of butyl benzyl phthalate in rats by gastric intubation. AB - Pregnant rats were given butyl benzyl phthalate (BBP) by gastric intubation at a dose of 0, 0.5, 0.75 or 1.0 g/kg on days 7-15 of pregnancy. In the 0.5 g/kg group, food consumption during the administration period was significantly decreased, but no adverse effect on the embryo-fetus was detected. High maternal lethality and complete resorption of implanted embryos in all the surviving dams were observed in the 1.0 g/kg group. Increased embryo-fetal death and decreased fetal weight were found at a dose of 0.75 g/kg which also caused reductions in maternal body weight gain and food consumption. A significantly and markedly increased incidence of fetal malformations was also detected in the 0.75 g/kg group. Cleft palate, fusion of the sternebrae and dilatation of the renal pelvis were mostly observed. PMID- 1609434 TI - Effect of scorpion Leiurus quinquestriatus (H&E) venom on rat's heart rate and blood pressure. AB - The effects of scorpion Leiurus quinquestriatus (H&E) venom collected from the South Sinai region, Egypt, on heart rate (HR) and mean arterial pressure (MAP) were studied after intramuscular administration of 3 different doses (100, 200 and 400 micrograms/kg) to anesthetized rats. The effects of adrenergic and cholinergic blocking agents on the venom-induced HR and MAP changes were also evaluated. In two groups of rats, propranolol or atropine were given before the venom administration. In the third group the venom was given before the injection of propranolol and atropine in combination. HR was measured by using a cardiotachometer coupler connected to an ECG coupler. MAP was calculated from the recorded arterial blood pressure (ABP) after catheterization of the left common carotid artery. Venom doses of 100 and 200 micrograms/kg produced tachycardia with a dose-response relationship, whereas 400 micrograms/kg evoked sinus tachycardia followed by bradycardia then tachycardia. MAP was elevated after the administration of each dose and reached its maximum value after 60 min with a dose-response relationship. Sinus, atrial and ventricular arrhythmias were observed from the recorded ECG during the time studied. This study revealed that the venom has pressor and depressor effects which are mediated through the autonomic nervous system. Propranolol reduced the stimulatory effects of the highest dose of the venom while atropine was effective in eliminating the depressor effect of the venom on HR. The arrhythmias induced by the venom were blocked by the injection of the two blockers and are assumed to be due to the release of catecholamines and acetylcholine. PMID- 1609435 TI - Uracil-induced urolithiasis in the urinary bladder of rats is irritation dependent. AB - The correlation between urolithiasis due to uracil administration and epithelial proliferation in the urinary bladder was investigated in male F344 rats. Animals, 6 weeks old at the start, which ingested 3% uracil alone in the diet for 4 weeks developed urolithiasis and papillomatosis of the urinary bladder, whereas addition of NaCl, particularly at high concentration (10%), to the 3% uracil in the diet blocked production of both. In contrast, NaHCO3 was without influence on either calculi or proliferative changes. These results indicate that uracil induced epithelial proliferation is due to direct mechanical irritation by calculi, and not to any chemical stimulus presented by uracil itself. PMID- 1609436 TI - Evaluation of murine lymphocyte membrane potential, intracellular free calcium, and interleukin-2 receptor expression upon exposure to 1,1-dimethylhydrazine. AB - The effects of 1,1-dimethylhydrazine (UDMH) on several early events associated with lymphocyte activation were examined. The concentration of intracellular calcium ([Ca2+]i) and membrane potential of murine lymphocytes were found to be altered upon exposure to UDMH; [Ca2+]i was increased in murine thymocytes, while splenocytes exhibited membrane hyperpolarization. In addition, interleukin-2 receptor expression induced by in-vitro concanavalin A stimulation of murine splenocytes at 24 and 48 h in the presence of UDMH was not affected. UDMH may interfere with the ability of these two distinct lymphocyte populations to regulate normal ionic fluctuations, thus contributing to altered immune responsiveness. PMID- 1609437 TI - Potentiation of lithocholic-acid-induced cholestasis by methyl isobutyl ketone. AB - Methyl isobutyl ketone was found to potentiate intrahepatic cholestasis induced by taurolithocholate and the combination of manganese-bilirubin. The aim of this study was to elucidate the mechanism of this potentiation using the lithocholate induced cholestasis model. Male rats were given methyl isobutyl ketone 7.5 mumol/kg body wt. daily for 3 days. The effect of this treatment on lithocholate induced cholestasis, bile formation and taurocholic acid transport was examined. The data showed that methyl isobutyl ketone treatment potentiated lithocholate induced cholestasis and reduced significantly bile salt, phospholipid and cholesterol secretion rates as well as the transport maximum of taurocholic acid. It is suggested that methyl isobutyl ketone potentiates lithocholate-induced cholestasis by reducing the bile salt pool and interfering with the haptic secretion rate of bile salts. PMID- 1609438 TI - Effect of seasonal variation on lipid peroxide level and glutathione peroxidase activity in the mouse before and after adriamycin administration. AB - We examined the effect of seasonal variation on lipid peroxide levels and glutathione peroxidase (GSHpx) activity in tissues of normal and adriamycin (ADR) treated mice. In the heart, normal lipid peroxide levels and GSHpx activity in November, December and January were lower than in other months. For the same period, lipid peroxide levels were higher and GSHpx activity lower in mice hearts after ADR administration. The results of GSHpx activity support those of lipid peroxide levels. We conclude that ADR-induced cardiotoxicity, related to the rise in level of lipid peroxide in mice hearts, is more likely to occur in winter than in other seasons. PMID- 1609439 TI - Altered protein kinase C activity and its endogenous protein phosphorylation in rat liver after administration of ethionine. AB - Ethionine, an ethyl analogue of methionine, induces fatty liver in rats. The effects of ethionine administration on protein kinase C (PKC) in rat liver was examined. By a single administration at a dose of 0.5 mg/g body wt., liver PKC activity was increased in both cytosolic and total particulate fractions. The increase in cytosol was significant, even at 4 h after administration, when compared with control rat liver cytosol. On the other hand, a 4-day consecutive administration (0.5 mg/g per day) resulted in decreased PKC activity, particularly in cytosol, when compared with the control. Protein phosphorylation in liver catalyzed by PKC was found to be enhanced by ethionine, irrespective of the mode of administration. The enhanced phosphorylation was observed in both cytosolic and total particulate fractions. The change of PKC activity, and the phosphorylation of its endogenous substrates, are postulated to be involved in the pathogenesis of ethionine-induced fatty liver of rats. PMID- 1609440 TI - Spontaneous neoplasms in aged CD-1 mice. AB - Spontaneous neoplasms in untreated control CD-1 mice (725 males and 725 females) used in carcinogenicity studies were evaluated and tabulated. The most common neoplasms in male mice were alveolar-bronchiolar adenomas (19.3%) followed by hepatocellular adenomas (11.0%), lymphoreticular neoplasms (6.8%), hepatocellular carcinomas (5.7%), Harderian gland adenomas (2.9%), alveolar-bronchiolar carcinomas (2.5%), and testicular interstitial cell tumors (1.9%). In the females, the most frequently occurring neoplasms were lymphoreticular neoplasms (16.4%) followed by alveolar-bronchiolar adenomas (12.3%), uterine endometrial polyps (4.3%), uterine leiomyomas (3.5%), mammary adenocarcinomas (2.5%), hepatocellular adenomas (1.8%), hemangiomas (1.7%), Harderian adenomas (1.7%), alveolar-bronchiolar carcinomas (1.5%), and pituitary adenomas (1.1%). Tumors in other various organs were found at a low incidence. PMID- 1609441 TI - Inhibition of Meth-A tumor cell proliferation in combined use of disulfiram with catalase. AB - The effect of combined use of disulfiram with catalase on Meth-A tumor cell proliferation was studied. The simultaneous addition of 5 x 10(-7) or 1 x 10(-6) M disulfiram with catalase (4-40 micrograms/ml) induced marked inhibition of cell proliferation. A moderate degree of the antiproliferative effect was also obtained by pretreatment of the target cells with 5 x 10(-6) or 1 x 10(-5) M disulfiram in the presence of catalase (40 micrograms/ml). These results suggest that compounds or metabolites with cytostatic activity are newly formed following the reaction of disulfiram with catalase. PMID- 1609443 TI - Enhanced hepatotoxicity of aflatoxin B1 in the rat by ethanol: ultrastructural changes. AB - The effect of ethanol pretreatment on aflatoxin B1 (AFB1)-induced ultrastructural alteration in hepatocytes was investigated in male Wistar rats. Pretreatment with 4 oral doses of ethanol (4.0 g/kg body wt. each) at 48, 45, 24 and 21 h prior to a single intraperitoneal administration of AFB1 (2.0 mg/kg body wt.) produced an alteration of fine structure more extensive than that observed after administration of AFB1 or ethanol alone. The organelles most affected were the mitochondria, endoplasmic reticulum and nucleus. The degree of nuclear edema, rough endoplasmic reticulum dilatation and mitochondrial swelling in hepatocytes from rats treated with ethanol and AFB1 was much greater than that of hepatocytes from rats treated with AFB1 or ethanol alone. Thus, ethanol may play a specific role in the potentiation of hepatic injury induced by AFB1 at the mitochondrial, endoplasmic reticular and nuclear level. PMID- 1609442 TI - Rhodamine B inhibits collagen synthesis by human lip fibroblasts in culture. AB - To investigate the effect of the cosmetic dye, rhodamine B, on the metabolism of collagen in fibroblasts, confluent KD cells, an established cell line of fibroblasts from human lip, were cultured for 6 h in a serum-free medium in the presence of the dye at 100 micrograms/ml and below. It was found that rhodamine B significantly decreased the content of procollagen type I C-terminal peptide antigen in both the cell layer and the medium with an only slight decrease in the cell number. Rhodamine B significantly decreased the incorporation of [3H]proline into either the collagen-digestible protein or the non-collagen protein in the cell layer. The incorporation of both [3H]thymidine and [14C]leucine into the acid-insoluble fraction of the cell layer was significantly decreased by rhodamine B; the activity of lactate dehydrogenase that leaked into the medium was not changed by the dye. From these results, it was suggested that rhodamine B has the capacity of decreasing the collagen content of the fibroblast cell layer of the human lip, which may result from a non-specific inhibition of protein synthesis without non-specific cell damage. Rhodamine B may impair the formation of extracellular matrix which is important for the maintenance of the lip tissue. PMID- 1609445 TI - Effect of scorpion Leiurus quinquestriatus (H&E) venom on the clinical chemistry parameters of the rat. AB - Egyptian scorpion venom was collected by electrical stimulation of the telson. Rats were injected with the lyophilized venom in 3 different doses (100, 200 and 400 micrograms/kg). Blood samples were drawn by heart puncture before and 4 h after venom administration. Serum was separated and collected for determination of glucose, blood urea nitrogen (BUN), creatinine, uric acid (UA), total proteins, cholesterol, sodium, potassium, calcium, inorganic phosphorus, alkaline phosphatase, aspartate aminotransferase (AST, GOT), alanine aminotransferase (ALT, GPT), lactate dehydrogenase and creatine phosphokinase (CPK). Serum glucose, creatinine, GOT, GPT and LDH were increased significantly in all treatments. At the same time serum BUN and CPK were elevated significantly with a dose-response relationship. On the other hand, serum total proteins, uric acid, cholesterol, calcium and potassium were significantly decreased 4 h after administration of the 3 doses. These changes in clinical chemistry parameters are most probably related to the toxic effect of the venom on the target organs. PMID- 1609444 TI - Hepatic accumulation and hepatotoxicity of luteoskyrin in mice. AB - HPLC analysis revealed that luteoskyrin administered orally to male mice accumulated selectively in the liver, with minor distribution to the serum and kidneys. Elevation of serum GOT and GPT values was maximal 3 days after administration. In mice administered this mycotoxin intravenously, selective accumulation was also observed in the liver, and the half-life of hepatic luteoskyrin in males was significantly longer than that in females. Increment of serum transaminases was also marked in males with maximum accumulation at 24 h after administration. Histopathologically, cellular membrane damage was an early effect of luteoskyrin on cell necrosis, and these morphological changes were also marked in males. Luteoskyrin also elevated hepatic lipid peroxides, the maximum elevation being 8 h after injection; this increase was suppressed by alpha tocopherol and Bi(NO3)3. HPLC-ECD analysis indicated that the level of 8-hydroxy deoxyguanosine, one of the markers of hydroxy-radical-mediated modification of DNA guanine residues, was increased in hepatic DNA. These findings indicate that luteoskyrin has a high affinity for the liver, resulting in induction of lipid peroxidation, hepatocellular membrane damage, and elevation of serum transaminase activities. It is suggested that the hydroxy radicals derived from this anthraquinone contribute to these toxicological changes. PMID- 1609446 TI - [The course of nursing home admission. A follow-up study in chronic and rehabilitation patients]. AB - This article describes the course of the nursing home stays of 157 newly admitted patients (55 years and older) using the Behaviour Rating Scale for Elderly Patients ('Beoordelingsschaal Oudere Patienten'). The follow-up period lasted maximally one year. Differences in the course in relation to the objective of the admission (rehabilitation versus continuous support) and possible factors which impeded or advanced the discharge of the rehabilitation patients, were investigated. For that purpose, information on diagnoses, prognosis, treatment goals and their achievement, and disability according to SIVIS (SIG Nursing Home Information System) was also obtained from the physicians in charge at the nursing home. The course of the nursing home stay appeared to differ for chronic and rehabilitation patients. In addition to physical disability and depressive behavior, the chronic patients, from the time of admission onwards, had more behavioural problems than the rehabilitation patients. Moreover, their dependency, physical and mental disability and inactivity increased in different degree during the stay. For two thirds of the rehabilitation patients, the stay did not end in discharge from the nursing home. For this group, the dependency, depressive behaviour, and to a lesser extent, aggressiveness increased during the stay. The outcome of rehabilitation appeared to be related to the extent of behavioural problems, to the level of disability, and to the medical condition on admission. The least disabled and the 'medically least complex' patients could usually be discharged with an improved level of functioning, which seemed to justify the nursing home stay. The absence of other services impeded discharge in a few cases.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609447 TI - [Respiratory disorders caused by tardive dyskinesia in psychogeriatric patients]. AB - Three case reports of antipsychotically induced tardive dyskinesia with prominent respiratory symptoms in elderly behaviourally disturbed patients are presented, followed by a discussion of the clinical picture and treatment of this relatively ill-known condition. It is not uncommon for the respiratory symptoms of tardive dyskinesia to be misdiagnosed as a pulmonary or psychogenic disorder. As an overall satisfactory treatment of tardive dyskinesia does not exist at present, reinstitution or increasing the dose of antipsychotics is sometimes the only effective way to suppress severe dyskinesia. PMID- 1609448 TI - [Promotion of competence in primary-care geriatrics]. PMID- 1609449 TI - [The Zung-12: a questionnaire for depression in the elderly]. AB - The reliability and validity for use in psycho-geriatric practice of a short and experimenter-rated version of the Zung (Self-rating) Depression Scale, the Zung 12, was studied. The subjects (N = 237) were aged 62 years or older and lived independently, in adapted dwelling, in homes for the aged, or received psychogeriatric daycare in psychogeriatric nursing-homes. It was concluded that the Zung-12 was sufficiently reliable (Cronbachs alpha = 0.85). According to factor analyses the test had high loadings on a depression factor and there were no loadings on a dementia factor. Age did not correlate with depression-scores. In comparison with other living situations the percentage of depressive persons in homes for the aged appeared to be high. Norms in the form of percentile scores were calculated separately for the homes for the aged and the remaining living situations. PMID- 1609450 TI - [Screening for dementia: validity of the Cognitive Screening Test (CST) and the Mini-Mental State Examination]. AB - The Cognitive Screening Test (CST--short version), a Dutch orientation questionnaire, and the Mini-Mental State Examination (MMSE) were compared with respect to their ability to discriminate between mildly demented, moderately demented and non-demented patients. The difference between mildly and moderately demented patients was based on the Global Deterioration Scale score. The CST and the MMSE were administered to patients who had been referred to the Memory Clinic of the University Hospital of Maastricht. Both instruments were successful in discriminating moderately and severely demented from non-demented patients. The CST and the MMSE were also successful with respect to the classification of depressive, non-demented elderly patients. The CST did not succeed in the correct classification of mildly demented patients (50% false-negative). The results of the MMSE in this group of mildly demented patients were moderate (25% false negative). It is concluded that the value of both screening instruments, and especially the short version of the CST is limited for clinical practice. PMID- 1609451 TI - Production and characterization of two monoclonal antibodies directed against the integrin beta 1 chain. AB - The production and characterization of two new monoclonal antibodies (MAbs), designated MAR4 and MAR5, raised against the partially purified alpha 5 beta 1 integrin, are described. The reactivity of these 2 MAbs on tumor cell lines indicated that they reacted on all the cells expressing the beta 1 subunit independently of the alpha 5 expression. Both MAbs were found to immunoprecipitate on 3 cell lines, a protein of 120 KD corresponding to the molecular weight be the beta 1 chain, in addition to proteins of other MW corresponding to the alpha subunits differentially expressed by these cells. The cross-competition experiments showed that MAR4 and MAR5 recognize the same epitope. These 2 MAbs seem to be useful reagents for the characterization of the VLA expression in tumor cells. PMID- 1609452 TI - Morphologic analysis of serous effusion cells by scanning electron microscopy. AB - The authors used scanning electron microscopy (SEM) to examine the cells obtained from serous effusions of patients affected with a neoplasm or benign disease. Cellular morphology was studied in non-neoplastic effusions to distinguish benign cells from cancer cells with which they are almost always suspended in malignant effusions. Tumor cells differ in some features such as shape, size, arrangement and especially in surface structures (microvilli), the latter being very noticeable when using this method. The investigation enabled us to note several changes in the cell surface that could reflect particular activities of the cells themselves. For this reason we believe that the technique may be considered very useful to gain knowledge of cellular morphology. However, it cannot be considered suitable for making routine diagnostic conclusions. PMID- 1609453 TI - Estimated incidence and prevalence of female breast cancer in Italian regions. AB - Female breast cancer incidence and prevalence in Italy have been estimated by region and vast areas from population-based survival data of breast cancer patients and 1970-1987 specific mortality data using a mathematical model. Italian age-standardized incidence rates (ASR) for 1987 range from 70 to 90 per 100,000 women-year in the Northern regions, 55 to 73 in the Center, and 45 to 72 in the South. Overall, the ASR is about 80 in the North, 70 in the Center and 60 in the South. In the absence of competitive mortality, breast cancer cumulative risk in the 0-74 years life span is about 7 women out of 100 in the North, 6 in the Center and 5 in the South. The decreasing risk pattern from North to Center then South appears less evident when under 45 age-specific rates are considered. Very high levels for young age-groups are present both in the North (Liguria and Emilia Romagna) and South (Sardinia and Apulia). The incidence pattern by age differs from region to region and over the considered period, suggesting that a birth-cohort effect is crossing the whole country. Using to model, it can be estimated that the risk by cohort increases from the generations born at the beginning of the century to those born in the 40s, after which, for subsequent generations, it has been decreasing in all the considered areas and is similar in the North and South. We can infer that for the whole country the incidence will increase up to the years 2000-2010 when those birth-cohorts at higher risk will also be at higher risk for age. In 1987, about 250,000 Italian women had a present or past history of breast cancer: for the 1970-1987 period, prevalence has increased by approximately 5,500 cases per year. PMID- 1609454 TI - Determinants of non-attendance to mammographic screening. Analysis of a population sample of the screening program in the District of Florence. AB - The characteristics associated with non-attendance to mammographic breast cancer screening were studied by interviewing a random sample (213 attenders, 121 non attenders in the 1989 screening) of residents in one of the municipalities of the Florence District Program, where screening has been ongoing since 1970. The overall attendance rate was 60%, and it was dependent on age (40-49 years, 66.5%; 50-59 years, 62.5%; 60-70 years, 55.5%), whereas a significant association with socio-economic status, educational level and health-behavior reported in other programs was not confirmed in the study. This finding suggests that determinants of non-attendance may vary and should be evaluated in each local setting. The belief that screening is useless, fear of cancer being detected, postponement and laziness were the most common motivations of refusal stated by non-attenders, and such a negative attitude towards screening was rather strong since most non attenders stated they would not like to be informed or stimulated to attend future screenings. Rapid improvement of attendance rates in such a context might be achieved only by putting special pressure on women aimed to change their negative attitude towards screening and their opinion about the benefits of early breast cancer detection. This might be regarded as unacceptable and however would involve high costs and a major organization effort. PMID- 1609455 TI - Combination of 5-fluorouracil, imidazole carboxamide, BCNU and prednisolone (FIB P) as a salvage chemotherapy in heavily pretreated breast cancer patients. AB - The results of treatment with 5-fluorouracil, imidazole carboxamide, BCNU and prednisolone (FIB-P) salvage chemotherapy in 60 patients with heavily pretreated advanced breast cancer are presented. For most of the patients (82%) this was the third line of chemotherapy. Performance status (ECOG) was 1, 2 and 3 in respectively 13, 27, and 20 patients. Predominant metastatic sites were: soft tissue (3/60, 5%), bone (22/60, 37%), and viscera (35/60, 58%). Tumor burden (number of affected organic systems) was 1, 2 and 3 or more in respectively 18, 24 and 16 patients. Average dose intensity received was 0.74 (range, 0.47-0.98); the average number of cycles was 3.8 (range, 2-8). Objective response (CR + PR) was observed in 22 patients (1 CR, 21 PR), with a response rate of 37% (22/60). Median duration of remission was 7 months (range, 3-15). Tumor burden was the only pretreatment patient characteristic that significantly influenced the remission rate (p less than 0.10). Dose intensity significantly affected tumor response (p less than 0.05). Toxic side effects (gastrointestinal disorders, alopecia and myelotoxicity) were generally moderate and tolerable. No treatment related death occurred. FIB-P proved to be an active salvage chemotherapy in heavily pretreated patients with advanced breast cancer. PMID- 1609456 TI - High dose alpha-2b interferon + folinic acid in the modulation of 5-fluorouracil. A phase II study in advanced colorectal cancer with evidence of an unfavourable cost/benefit ratio. AB - The combination of folinic acid (FA) and 5-fluorouracil (5FU) is the most active systemic chemotherapy against advanced colorectal cancer. Experimental and clinical studies have suggested that the activity of 5FU can be improved by the addition of alpha-interferon (IFN). To evaluate the possibility of a double modulation of 5FU, a pilot study was conducted in the period July 1989-December 1989 with the following regimen: FA (200 mg/m2 i.v. bolus x 5 days) + 5FU (400 mg/m2 i.v. in 15 min x 5 days) + alpha-2b IFN (10 x 10(6) IU subcutaneously on alternate days). FA and 5FU administrations were repeated every 28 days; IFN was administered every week. In the 16 treated patients, 4 partial responses, 4 no changes, and 8 with progression of disease were observed, with an objective response rate of 25% (95% CI, 7.8%-55.1%). Median duration of response was 9.5 months, as was overall survival. Toxicity (fever, fatigue, neurotoxicity, stomatitis and diarrhea) was considerable and led to a reduction in IFN doses in 10/16 patients. Due to the unfavorable cost/benefit ratio, the study was closed and a new trial, with different doses and schedule of IFN, was started within the GISCAD (Italian Group for the Study of Digestive Tract Cancer). PMID- 1609457 TI - Bilateral breast involvement in a 71-year-old white man with lambda light chain disease. Regression after a new chemotherapy combination. A case report. AB - A rare case of lambda light chain disease with bilateral breast involvement is described. A complete regression after a new chemotherapy combination (peptichemio + teniposide + dexamethasone) was obtained. A previous treatment with prednisone + melphalan was ineffective. PMID- 1609458 TI - Intracystic papillary carcinoma of the male breast. A case report (histochemical, immunohistochemical and ultrastructural study). AB - We report a case of intracystic papillary carcinoma of the male breast in a 70 year-old male Caucasian. Grossly, the tumor was a cystic lesion measuring 6 cm in diameter. It contained hemorrhagic fluid and a mural nodule with filiform projections. PAS stain with and without digestion revealed small clumps of diastase-resistant material in the cytoplasm of the neoplastic cells. Grimelius stain was positive. Immunoperoxidase stains were negative for neuron-specific enolase, S100 protein, cromogranin and synaptophysin and were positive for carcinoembryonic antigen and epithelial membrane antigen. On ultrastructural examination the neoplastic cells showed membrane-bound, dense-core secretory granules. We believe that this neoplasm, despite negative neuroendocrine markers, is a variant of mammary adenocarcinoma with endocrine differentiation, partly because of the positive Grimelius stain and partly because of the presence of electron-dense granules, which according to some authors represent lactational differentiation. PMID- 1609459 TI - Osteogenic sarcoma of the breast. A case report. AB - A case of primary osteogenic sarcoma of the breast is reported. It should be distinguished from carcinoma with extensive osseous metaplasia. The results of light and electron microscopy including an immunohistochemical study are presented. Immunohistochemical and ultrastructural studies proved that the lesion, in the absence of epithelial differentiation, was a primary osteogenic sarcoma of the breast rather than a carcinoma with extensive osseous metaplasia. Diagnosis may be delayed because the tumor is confused clinically and mammographically with a calcific fibroadenoma. PMID- 1609460 TI - Spontaneous rupture of spleen in a patient with splenic metastasis of melanoma. A case report. AB - We report a case of spontaneous splenic rupture in a patient with metastatic melanoma. Spontaneous splenic rupture without previous trauma has been observed in various pathological conditions such as infectious mononucleosis, malaria, typhoid fever and, rarely, neoplasms affecting the spleen. There have been several reported cases of splenic rupture in leukemias. Despite the high incidence of splenic metastases in metastatic melanoma, there have been only 3 cases of spontaneous splenic rupture reported in the past. PMID- 1609461 TI - Dermatofibrosarcoma protuberans metastatic to the lung. A case report. AB - A case is presented of dermatofibrosarcoma protuberans of the gluteal region with metastasis to the lung appearing 7 years after wide excision of the primary lesion. The world literature is reviewed. The clinical and pathologic features of dermatofibrosarcoma are reviewed and treatment is discussed, with the aim of emphasizing the need for long-term follow-up examination of lymph nodes and for metastases following wide excision of these lesions. PMID- 1609463 TI - Angiomyolipoma in the transplanted kidney. A case report. AB - Angiomyolipoma is a very rare benign renal tumor. This paper presents the autopsy finding of an angiomyolipoma in the transplanted kidney. PMID- 1609462 TI - Heterogeneity and phenotypic instability of chemotherapeutic and immunologic sensitivity in murine and human melanoma cell clones. AB - The aim of the present study was to examine the phenotypic heterogeneity of murine and human melanoma cell lines with particular reference to anticancer drug sensitivity, growth pattern and susceptibility to lysis by lymphokine (rIL2) activated killer (LAK cells). Clones selected for a different drug sensitivity were tested to evaluate the stability of such properties after different in vitro passages. A possible relationship between drug sensitivity and LAK susceptibility was also analyzed. The results indicated a high heterogeneity in murine and in human melanoma clones for all the parameters. However, drug sensitivity, which was stable although for only a few passages in an untreated human melanoma, was highly unstable in murine naturally or drug-induced resistant cells. Finally, whereas human drug-resistant clones were sensitive to lysis by LAK cells and an inverse correlation was found with the level of drug resistance, murine clones appeared to be LAK sensitive, and no correlation was found between the level of drug resistance and LAK sensitivity. Our data indicate a different stability in drug response of human and murine cells and a different behaviour of human and murine drug-resistant cells in response to LAK lysis. PMID- 1609464 TI - Adenocarcinoma of unknown primary site with bone marrow and orbital metastases suggestive of a prostatic origin. AB - Prostate cancer may occasionally present as an adenocarcinoma with an undetermined primary site. We report a case in which bone marrow invasion and orbital metastasis were the first evidence of malignancy. Recognition of metastatic prostate cancer is important since it can be managed safely and effectively with hormonal therapy. PMID- 1609465 TI - Primary mucoepidermoid carcinoma of the liver. A case report. AB - The authors report a case of primary mucoepidermoid carcinoma of the liver in a 66-year-old woman. Electron microscopy findings suggest an origin from the biliary epithelium as well as cholangiocarcinoma, which clinical and prognostic features are similar to those of mucoepidermoid carcinoma. PMID- 1609466 TI - Multisystemic eosinophilic epitheliotropic disease in a horse: attempted treatment with hydroxyurea and dexamethasone. AB - Equine multisystemic eosinophilic epitheliotropic disease is rare in horses. The clinical signs vary according to the organs affected, the skin and gastrointestinal tract being most commonly involved. This paper gives the first reported description of a horse with multisystemic eosinophilic epitheliotropic disease in the United Kingdom and the attempts to treat it. The horse showed dermatological, gastrointestinal, hepatic, pulmonary and pancreatic involvement. Some improvement was seen when the horse was treated with corticosteroid and hydroxyurea. PMID- 1609467 TI - Airborne infection of laying hens with Salmonella enteritidis phage type 4. AB - Hens were exposed to small-particle aerosols containing different concentrations of Salmonella enteritidis phage type 4. They developed a systemic infection and some birds were still excreting the organism in the faeces when killed 28 days after infection. S enteritidis was present for a similar period in a wide range of alimentary tract issues and in the ovary and oviduct. PMID- 1609468 TI - Suspected botulism in three intensively managed Australian cattle herds. AB - Serious outbreaks of a paralytic disease in cattle occurring in the spring and summer of 1988 were investigated on three farms in south eastern Queensland, Australia. On one farm 237 (31 per cent) of 770 cattle died, on the second 109 (40 per cent) of 271 cattle died and on the third 30 (8 per cent) of 380 cows died. Botulism was suspected on the basis of the clinical signs, the lack of significant pathology, a failure to incriminate other agents and a positive feeding trial in one sheep. Laboratory tests for the presence of botulinum toxin failed to confirm this diagnosis, and further feeding trials using ingredients of two rations were also negative. PMID- 1609469 TI - A case of calf craniopagus in Trinidad. PMID- 1609471 TI - Code of practice for the treatment of sick and injured strays. PMID- 1609470 TI - Small colon intussusception associated with an intralumenal leiomyoma in a pony. PMID- 1609473 TI - Economic realism. PMID- 1609472 TI - Myxomatosis vaccine. PMID- 1609474 TI - Investigation of the effects of transport and lairage on hydration state and resting behaviour of calves for export. AB - Plasma sodium concentrations, packed cell volume, total plasma protein concentration and dermal skinfold thickness were used to assess the state of hydration of 113 transported calves before and after lairage and in 30 control calves on the farm of origin. Skin thickness increased significantly (P less than 0.05) and total protein increased slightly during transport and decreased during lairage. These changes suggest that transport may cause dehydration and lairage may help in recovery. Plasma potassium concentration decreased during transport, but the effect was inversely related to the distance travelled, and the concentration increased during lairage. These changes are consistent with recovery from initially high cortisol levels at loading. The resting behaviour of 150 transported calves was recorded hourly for six hours. More time was spent resting and sleeping by the transported calves than has been reported for non transported calves and more still by small transported calves, suggesting that transport is exhausting, that lairage helps recovery and that small calves are more adversely affected. During lairage the numbers of calves asleep decreased to values reported for normal calves, suggesting that 10 hours lairage was adequate. However, small calves did not return to their normal rest patterns within the observation period. PMID- 1609475 TI - Chlamydia psittaci infection in horses: results of a prevalence survey and experimental challenge. AB - Nasal and conjunctival swabs were obtained from 300 horses and Chlamydia psittaci was isolated from 15 of them (5 per cent). Eleven nasal swabs and six conjunctival swabs were positive on culture, but there was no association between the isolation of the organism and the presence of clinical ocular or respiratory disease. Six ponies were challenged with an equine isolate of C psittaci into the eye, nasal cavity or bronchial tree. The organism could be isolated from nasal and conjunctival swabs taken from the ponies for up to 17 days after challenge, but there was no clinical evidence of disease. PMID- 1609476 TI - Consistency of results from the Vettest 8008 clinical biochemistry analyser. AB - Findings are presented on the precision of a clinical biochemistry analyser designed specifically for veterinary use. Twenty biochemical analytes have been examined in detail for variation within and between runs. The results indicate that the analyser can provide high precision for all the analytes with the possible exception of calcium, and suggest that the instrument can be used with confidence in the practice laboratory to aid diagnosis and to monitor biochemical changes in animals receiving treatment. PMID- 1609477 TI - Ultrasonography as an aid to controlled breeding in the llama (Lama glama). AB - An ultrasonic linear array scanner with a transrectal probe was used to observe ovarian and uterine changes associated with the reproductive cycle in llamas. 'Waves' of follicular development and regression occurred in unstimulated females, during which the dominant follicle reached a maximum size of 9 to 13 mm; both ovaries were equally active. Ovulation was induced by mating in 80 per cent of cases, and when mating was accompanied by the administration of human chorionic gonadotrophin the ovulation rate increased to 90 per cent and the time to ovulation decreased from two to three days to one to two days. Some spontaneous ovulations occurred. Corpora lutea reached a maximum size of 12 mm (non-pregnant) or 14 mm (pregnant) after seven or 16 days, respectively. The lifespan of the corpus luteum was approximately 11 days in non-pregnant llamas and the regression time was advanced by the administration of prostaglandin or embryo recovery. Pregnancy could be diagnosed as early as 19 days after mating. PMID- 1609478 TI - Milk progesterone profiles in untreated cystic ovarian disease. PMID- 1609479 TI - Cystostomy in a cat with urethral trauma. PMID- 1609480 TI - Salmonella enteritidis PT4: broiler breeder flock breakdowns. PMID- 1609481 TI - Bone scanning for back problems in horses. PMID- 1609482 TI - Canine requirement for dietary arginine. PMID- 1609483 TI - Ivermectin in guinea pigs. PMID- 1609484 TI - Toxicologic evaluation of injectable acemannan in the mouse, rat and dog. AB - Acemannan, the USAN-accepted name for long-chain polydispersed beta-(1,4) acetylated polymannose with interspersed 0-acetyl groups with a mannose monomer/acetyl ratio of approximately 1:1 and extracted from Aloe vera (barbadensis Miller), was administered as a 1.0 mg/ml solution to mice, rats and dogs, either as single dose or repeated at 4-d intervals for 8 doses by iv or ip routes. No significant signs of intoxication and no deaths occurred in animals treated with the single injection of acemannan at dosages of 80 mg/kg iv or 200 mg/kg ip in mice, 15 mg/kg iv or 50 mg/kg ip in rats, and 10 mg/kg iv or 50 mg/kg ip in dogs. On repeated injections systemic toxicity was limited to obvious transient discomfort that appeared dose related. There was accumulation of macrophages and monocytes without subsequent inflammatory reaction in lungs of the iv-treated animals, and in liver and spleen and on peritoneal surfaces of ip treated animals. The effects were not considered adverse, but were consistent with the known immune stimulating activity of acemannan. A few deaths occurred in mice and rats that were suggestive of resulting from improper injection or sequella of necrosis of the injection site. The NOAELs for acemannan determined from these repeated injection studies were 20 mg/kg iv or ip in the mouse, 4.0 mg/kg iv and 50 mg/kg ip in the rat, and 1.0 mg/kg iv in dogs; 5.0 mg acemannan/kg ip in the dog was considered to be LOAEL, based on the emesis and abdominal discomfort induced. PMID- 1609485 TI - In vitro ruminal metabolism of larkspur alkaloids. AB - Larkspur (Delphinium sp) poisoning of range cattle is a serious, recurring problem in the western United States. Numerous stratagems have been recommended to ameliorate larkspur intoxication, but none are completely effective. Previous studies in this laboratory indicated bovine ruminal microflora are capable of chemically modifying Delphinium alkaloids. Research reported herein was undertaken to further evaluate whether differences in ovine and bovine rumen metabolism might explain differences in susceptibility to larkspur intoxication and whether existing metabolic activity can be enhanced by sustained exposure to Delphinium alkaloids. Comparison of ovine and bovine rumen metabolism of Delphinium geyeri alkaloids in vitro failed to demonstrate differences in the rate of alkaloid metabolism. Rumen liquor collected sequentially from a fistulated cow dosed with dried Delphinium geyeri did not vary in ability to metabolize larkspur alkaloids. PMID- 1609486 TI - The effect of dietary supplements on chronic bitterweed (Hymenoxys odorata) poisoning in sheep. AB - Two experiments were designed to establish a chronic bitterweed dose in sheep and to study the prevention of chronic bitterweed poisoning with dietary supplements of high protein (20% crude protein) and sodium sulfate. The first experiment consisted of 5 lambs in each of 3 groups. The low dose received up to 5.0 g bitterweed/kg/day which was equivalent to 10 mg hymenoxon/kg bw. The high dose group received a maximum bitterweed dose of 1 g/kg/day or 20 mg hymenoxon/kg. The final average weights of the low (29 kg) and the high (30 kg) dose groups were significantly different from the control (40 kg) group. The prophylactic experiment consisted of 5 groups of 4 sheep each. Each group received a different combination of bitterweed, a basal ration, soybean meal, urea, or sodium sulfate. The soybean meal and urea were used to adjust the ration to 20% crude protein, and each animal received 1.2 g bitterweed/kg/day. The high protein-sodium sulfate diet did not prevent chronic bitterweed toxicity, but soybean meal-sodium sulfate combination had the greatest effect on the reduction of bitterweed toxicity. Urea potentiated the toxic effects of bitterweed. PMID- 1609487 TI - Alcohol and motorcycle riders: a comparison of motorcycle and car/truck DWIs. AB - Alcohol's effects on balance and motor coordination would be expected to have greater consequences for motorcycle riders than car/truck drivers. Driving while intoxicated/under the influence (DWI) reports for 1984 and 1985 from the San Antonio, TX, Police Department were reviewed to evaluate motorcycle DWIs, and to compare them with car/truck DWIs. During the 2-y period there were 100 DWI reports involving motorcycle riders, which were compared to 100 involving car/truck drivers. Motorcycle riders were all male and younger (mean 26 y) than car/truck drivers (p less than 0.05). Initiation of the DWI investigation of motorcycle riders was more frequently due to excessive speed, and less likely due to an accident, when compared to car/truck investigations. Breath alcohol testing demonstrated a significantly lower blood alcohol concentration in motorcycle riders, 0.14 +/- 0.05 g/dL, than in car/truck drivers, 0.16 +/- 0.05 g/dL (p = 0.016). The results of this study suggest that alcohol influences motorcycle riders to a greater extent than it does car/truck drivers. Further data is needed to determine whether lower blood alcohol concentration limits should be considered for the definition of "driving while impaired" in motorcycle riders. PMID- 1609488 TI - Palicourea marcgravii intoxication in rats: effects of different fractions. AB - Palicourea marcgravii (Pm) is the most toxic plant in Brazil to cattle. Previous experiments showed that Pm experimental intoxication in rats is similar to that reported for cattle, and these symptoms include generalized itching, incoordination, depression, tonic-clonic seizures and death. The present study was undertaken to verify if the toxic principle of Pm responsible for seizure and death is the same that produces itching and depression. Rats that received Pm aqueous or chloroform fractions showed itching, while depression, seizures and death were associated with the aqueous fractions. These results suggest that Pm contains at least 2 active compounds, one causing itching and another one promoting depression, seizure and death. PMID- 1609489 TI - The influence of 2,3-butanedione monoxime on dichlorvos-induced enzymatic changes in buffalo calves. AB - The effects of administration of 2,3-butanedione monoxime (2,3-BM) or atropine alone and in combination were determined on the blood enzymatic activities of dichlorvos-exposed buffalo calves. Dichlorvos given po at 160 mg/kg body weight produced pronounced inhibition of erythrocyte acetylcholinesterase (AChE) and elevation in serum aminotransferases and phosphatases within 30 min. 2,3-BM administered alone or in conjunction with atropine to dichlorvos-exposed calves significantly reactivated erythrocyte AChE activity whereas atropine was ineffective. The effect of 2,3-BM plus atropine on other enzymatic activities was comparatively greater than that of either drug alone. The results indicated that combined treatment with 2,3-BM and atropine was most effective in reversing dichlorvos-induced enzymatic alterations. PMID- 1609490 TI - Experimental Azadirachta indica toxicosis in chicks. AB - Brown Hisex chicks were fed Azadirachta indica ripe fruit at 2, 5 or 10% of basic diet from their 7th to 35th d of age. Decreased body weight gain and efficiency of feed utilization and hepatonephropathy were most severe in chicks fed the 10% A indica diet. These changes were accompanied by anemia and increases in LDH, GOT and ALP activities and uric acid concentration and by decreased serum total protein. Hepatocytes and renal tubular cells did not completely revert to normal 2 w after removal from the test diets. PMID- 1609491 TI - Effects on chicks of Balanites aegyptiaca kernel saponin given by different routes of administration. AB - The effect of oral or parenteral administration of crude saponin extract from Balanites aegyptiaca seed kernal on Hisex-type chicks was studied. Seven-d-old chicks were given 5 mg Balanites crude saponin/kg/d im, 25 mg/kg/d ip or 250 mg/kg/day po for 3 w. When compared to controls, the body weights of dosed chicks were depressed and serum LDH and GOT activities and uric acid concentrations were significantly elevated. There were no consistent differences in serum GGT, CPK, total cholesterol and total protein between control and dosed birds. The main lesions were fatty cytoplasmic vacuolation and necrosis of hepatocytes, lymphocytic nodules, epithelial cell degeneration of the renal tubules, catarrhal enteritis and varying degrees of hemorrhage in the thigh and breast muscles. Myositis or peritonitis were observed in chicks given Balanites crude saponins im or ip, respectively. PMID- 1609492 TI - Effect of monensin on liver glutathione, glutathione S-transferase and monooxygenases in rats. AB - Monensin administered ip to male rats at a dosage of 2.5 mg/kg/d for 3 consecutive days did not change the liver levels of glutathione, but depressed significantly the amount of cytochrome P-450 and the activities of aniline hydroxylase and a cytosolic CDNB-specific glutathione S-transferase. There was a marked decrease in the aminopyrine N-demethylase activity and a significant increase in the pentobarbital sleeping time in rats treated with monensin. In contrast, no change in these parameters was found 2 h after a single ip dose (7.5 mg/kg) of monensin. The results suggest that monensin-induced inhibition of the liver cytosolic glutathione S-transferase and microsomal monooxygenases is non specific. PMID- 1609493 TI - The influence of single topical application of dichlorvos on blood esterases and toxicity in male calves. AB - The effect of dichlorvos on inducing changes in blood esterase activities and systemic toxicity was investigated following single topical applications of 1, 3 or 6% dichlorvos concentrations to male calves. Dichlorvos at 1% concentration did not produce any signs of toxicity, whereas 3 and 6% concentrations induced mild to severe toxicity characteristic of anticholinesterase poisoning. Dichlorvos at all concentrations significantly inhibited erythrocyte cholinesterase (25-75%), plasma cholinesterase (30-85%), and serum carboxylesterase (15-51%) activities in male calves. The dose-dependent inhibition was maximum 12 h after insecticide exposure. The extent of inactivation of blood esterases was not correlated with the severity of toxicity. Inhibition of blood cholinesterases by the 6% dichlorvos was still present 21 d after the dichlorvos exposure. PMID- 1609494 TI - Blood chromium and nickel in relation to respiratory symptoms among industrial workers. AB - Seventy-eight workers exposed to fumes and dust of nickel and chromium in their occupation in the glass industry were studied for respiratory symptoms in relation to nickel and chromium concentrations in their blood. A significant (p less than 0.01) association was observed between respiratory symptoms and elevated blood nickel and chromium. An interaction between nickel and chromium was found in relation to the prevalence of respiratory symptoms. PMID- 1609495 TI - Chinese patent medicine as a potential source of mercury poisoning. AB - This research is an effort to create an awareness of the potential hazards of some Chinese patent medicines which contain mercurial ingredients. This should be of consideration when screening symptomatic patients who are of Asian ethnic background or other users of these medicines. This research discusses reported cases of mercury poisoning related to the use of Chinese patent medicines and the potential toxicity of cinnabar (red mercuric sulfide) and calomel (mercurous chloride), 2 mercurials commonly used in these medicines. A list of mercurial containing Chinese patent medicines available on the open market in North America has been compiled, together with their traditional uses and mercurial contents and is presented as a quick reference for Specialists in Poison Information. This class of medicine may not pose a problem when used appropriately; however, its misuse, abuse, overdosage and improper storage can lead to serious mercury poisoning. PMID- 1609496 TI - Suspected buttercup (Ranunculus bulbosus) toxicosis with secondary photosensitization in a Charolais heifer. AB - A presumptive diagnosis of buttercup toxicosis with photosensitization secondary to hepatotoxicity was made in an 18-mo-old Charolais heifer. The differential diagnosis included salmonellosis, aflatoxicosis, bovine virus diarrhea, internal parasite infestation, and plant toxicosis with either primary or secondary photosensitization. All these possibilities were excluded except buttercup toxicosis with photosensitization secondary to hepatotoxicity. While this diagnosis was not absolutely confirmed, it was the most likely cause of the disease and raised the intriguing possibility that protoanemonin, buttercup's toxic principle, is hepatotoxic. PMID- 1609497 TI - A case of fatal methyl bromide poisoning. AB - A case of preventable fatality and a nearly greater disaster as a result of methyl bromide fumigation of a restaurant is presented. Methyl bromide is a nearly odorless, volatile hydrocarbon used as a fumigant in the food industry. As a result of this episode, recommendations are made for worker and community notification of the hazards involved whenever fumigation takes place. Addition of a mucosal irritant or olfactory stimulant is recommended to provide warning for methyl bromide exposure. PMID- 1609498 TI - Senecio spp poisoning in cattle in southern Brazil. AB - Epidemiological, clinical, necropsy and histopathological data were accumulated during the study of 15 outbreaks of Senecio spp poisoning in cattle occurring during the last 3 y in the State of Rio Grande do Sul, Brazil. Morbidity averaged 17% and mortality was virtually 100%. The peak mortality occurred during spring and early summer. The most constant clinical signs included anorexia, depression, tenesmus often followed by rectal prolapse, and rough hair coat. Affected animals remained apart from the rest of the herd, lost weight, presented ascites, and had signs of digestive and neurological disturbances. Icterus, photodermatitis, polydipsia, and dependent subcutaneous edema were occasionally noticed. Two main clinical courses could be distinguished. In the protracted form, progressive weight loss terminated with death within many weeks or months. Alternatively, an acute or subacute course led to death in a few days. In both forms, necropsy and histopathological findings included diffuse fibrosis of the liver, hepatomegalocytosis, and biliary hyperplasia. Extrahepatic lesions included gastrointestinal and mesenteric edema, distension, edema and adenomatoid hyperplasia of the gallbladder, and spongy degeneration of the cerebral white matter. S brasiliensis and S oxyphyllus were the species involved in the field outbreaks. PMID- 1609499 TI - A case of monensin poisoning in ostriches. AB - A clinical case of monensin poisoning in ostriches is presented. Analytical results and histopathologic changes in intercostal muscles and liver supported the ionophore toxicity diagnosis. PMID- 1609500 TI - Poisonings in animals: a 1990 report of the American Association of Poison Control Centers. PMID- 1609501 TI - The biology and pathology of programmed cell death (apoptosis). AB - Apoptosis is a process by which cells die in a controlled and programmed manner in response to specific stimuli, often following extrinsic and intrinsic signals which ultimately cause the "switching on" of cell death regulatory genes. Condensation of chromatin and cytoplasm, fragmentation of the cell and formation of membrane-bound bodies containing intact organelles (apoptotic bodies), and phagocytosis of these bodies by resident cells are the major structural changes associated with apoptosis. Biochemically, activation of a nonlysosomal endonuclease is a cardinal feature of this mode of cell death. Several genes have been implicated in the execution of apoptosis. A signal transduction mechanism is suspected to regulate the phenomenon. Although apoptosis is widely considered as an adaptive response to physiological or near physiological stimuli, several noxious agents can initiate the reaction and thus it is often a toxicological response. PMID- 1609502 TI - Heavy metal poisoning in ostriches from proventricular foreign bodies. AB - Cases of iron, zinc, lead and copper poisoning in ostriches are discussed. Metallic proventricular foreign bodies are a potential source of heavy metal poisoning in ratites. Tissue levels of heavy metals and trace elements supporting these diagnoses are reviewed. PMID- 1609503 TI - Polychlorinated biphenyls: an overview of metabolic toxicologic and health consequences. AB - Polychlorinated biphenyls (PCBs) are complex mixtures of chlorinated aromatic hydrocarbons which are classified as lipophilic xenobiotics in vivo. Because of their unusual thermal and insulating properties, widespread use in industry was commonplace. They eventually gained entry into the biota, and their diffuse distribution represents both a potential and actual risk to humans and animals due to their bioconcentration in the food chain and toxicity secondary to accidental occupational or environmental exposure. Experimental poisoning in various animal models demonstrates that PCBs are potent inducers of hepatic microsomal enzyme systems, transmitted transplacentally and produce reproductive dysfunction. They alter immune function by decreasing the cell-mediated response and, in addition to producing myriad manifestations, are tumorigenic. Human exposure to PCBs has been associated with similar abnormalities, but because of limited data their chronic toxicity has not been well established. This is the key problem to evaluating possible untoward health effects in humans. PMID- 1609504 TI - The epidemiology of poisoning: a monitoring program for developing countries. AB - The epidemiology of poisonings continues to challenge reliable scientific results. This paper reviews global, national and regional efforts to verify and quantify the incidence of morbidity and mortality from toxic agents, especially from agricultural pesticides. It proposes a multifactorial program be installed in a defined region to be used as a standard model for the epidemiology of poisonings. PMID- 1609505 TI - Cocaine in pregnancy: analysis of fetal risk. AB - During the last decades there has been a substantial increase in the recreational use of cocaine in young adults and parallelly there has been an increase of its use by pregnant women. We analyzed all published papers on cocaine use in pregnancy and found that for most endpoints studied (eg, prematurity, head circumference) there were many studies showing effects and many showing no effects. Upon meta-analysis, most of these effects could not be shown significant when compared to control groups. In a prospective study in Toronto, babies exposed to cocaine during the first trimester only had Bayley scores at 18-mo of life that were identical to unexposed babies or to those exposed to canabinoids. Motherisk presently counsels women who discontinue cocaine use in the first trimester of pregnancy that there is no increased developmental risk for the baby. PMID- 1609506 TI - Heart leaf poison bush (Gastrolobium grandiflorum) toxicity in a western Queensland sheep flock. PMID- 1609507 TI - The impact of megakaryocyte proliferation of the evolution of myelofibrosis. Histological follow-up study in 186 patients with chronic myeloid leukaemia. AB - A histological study on sequential bone marrow biopsies in patients with chronic myeloid leukaemia (CML) was performed. We wished to answer the question as to whether a different content of megakaryopoiesis in the bone marrow of CML patients has a prognostic significance for the development of myelofibrosis during the course of disease. In addition, the significance of possible changes in the quantity of megakaryopoiesis in this process was assessed. In 186 patients who had no fibre increase at first diagnosis, the rate of subsequent myelofibrosis varied from 19% for the common or granulocytic subtype (CML.CT) to 40% for patients with features of megakaryocytic increase (CML.MI). No significant differences were found either in the rapidity of progression to fibrosis or in the final rate of osteomyelosclerosis. Whereas in CML.MI most patients (75%) showed an increase of fibres only, this was accompanied by an additional increase of megakaryocytes in CML.CT, changing the histological pattern from CML.CT to .MI or .MP, respectively. The data therefore revealed a correlation between fibre increase and subtyping of CML as suggested by the Hannover classification of chronic myeloproliferative diseases. Subtypes of CML with megakaryocytic increase could be shown to present a "pre-myelofibrotic" stage of disease and may therefore be conceived as a particular pathway of acceleration. PMID- 1609508 TI - Nephrosclerosis and aortic atherosclerosis from age 6 to 70 years in the United States and Mexico. AB - With increasing age, the thoracic aorta shows progressive fibroplastic intimal thickening, which is thought to be pre-atheromatous. A similar progressive intimal thickening in the renal cortical arteries is the distinguishing feature of the nephrosclerosis which underlies essential hypertension. Therefore, the earliest detectable youthful precursors of atherosclerosis and hypertension show strong morphological resemblances to each other. In this study, close statistical associations have been shown between the two types of arterial intimal fibroplasia. Both conditions show similar sigmoid growth curves from ages 6 to 70 years, thereby generating correlations across age groups of r = 0.99 in New Orleans and r = 0.95 in Mexico City. Specimens gathered in New Orleans were found to have about 1.4 times greater arterial intimal thickening than specimens from Mexico City, and this excess was seen at all ages in both the aortas and the renal cortical arteries. It seems likely that intimal fibroplasia of arteries is reflecting similar biological principles at all levels of the vascular tree. Whatever etiological factors vary between New Orleans and Mexico City, those factors appear to act directly at a tissue level to promote the early precursors of atherosclerosis and of the nephrosclerosis that underlies hypertension. PMID- 1609509 TI - Helicobacter colonization and histopathological profile of chronic gastritis in patients with or without dyspepsia, mucosal erosion and peptic ulcer: a morphological approach to the study of ulcerogenesis in man. AB - Helicobacter pylori colonization and the incidence, severity, activity and topography of gastritis were investigated systematically in antrum and corpus mucosal biopsies of 1177 subjects undergoing endoscopy in the absence of gastric complaints (asymptomatic, 49) or for non-ulcer dyspepsia (NUD; 631 patients, 72 of whom had gastric and/or duodenal erosions), active gastric ulcer (GU, 76 patients), active duodenal ulcer (DU, 138 patients), and healed gastric (HGU, 39 cases) or duodenal ulcer (HDU, 230 cases). In the antrum, H. pylori colonization and the incidence, severity and activity of gastritis increased progressively in the sequence asymptomatic, erosion-free NUD, erosive NUD, healed ulcer and active ulcer. The same trend was observed in the corpus as regards H. pylori and gastritis incidence, whereas the severity and activity of gastritis were lower in active DU and erosive NUD and higher in active, proximal GU than in the remaining patients. Active DU and erosive NUD showed the highest incidence of non-atrophic gastritis and lowest type-A or AB atrophic gastritis, while active GU had lowest normal mucosa or type-A gastritis and highest type-B atrophic gastritis. In conclusion, H. pylori colonization and gastritis incidence, severity and, especially, activity of the antrum might all contribute to mucosal erosion and ulceration, whereas the same factors, at least in part and with the exception of proximal GU, seem to have a preventive role when affecting corpus mucosa. PMID- 1609511 TI - Usefulness of a novel monoclonal antibody against human osteocalcin in immunohistochemical diagnosis. AB - A novel monoclonal antibody against human osteocalcin, recently established in our laboratory, was shown by immunoblotting and immunohistochemistry to react specifically with human osteoblasts. In the present study, the antibody was applied to the immunohistochemical diagnosis of human bone tumours, especially osteoblastic tumours. The antibody reacted with all 27 osteosarcomas. No positive reaction was found either in chondrosarcoma, giant cell tumours of bone, soft tissue tumours or epithelial tumours. A positive reaction was found preferentially in the cytoplasm of most of the osteosarcoma cells, but not in the extracellular matrix. Since the antibody reacted with formalin-fixed and paraffin embedded tissues, it will be a useful tool for routine immunohistochemical diagnosis of osteoblastic lesions. PMID- 1609510 TI - Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells, non-vascular interstitium and capillaries: a stereological study on rat hearts. AB - The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P less than 0.001). Capillary density (QA) was decreased in transverse sections (P less than 0.01) and increased in longitudinal sections (P less than 0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium. PMID- 1609512 TI - The renin-secreting cell and the glomerular peripolar cell in renal artery stenosis and Addison's disease. AB - The glomerular peripolar cell may be a secretory component of the juxtaglomerular apparatus. To investigate this hypothesis we studied kidneys with the renin angiotensin system activated by two different stimuli in order to compare the responses of peripolar cells and renin-secreting cells. We examined 10 human kidneys, removed for renal artery stenosis and 11 autopsy cases of Addison's disease with appropriate controls. We counted granulated peripolar cells in serial paraffin-embedded sections and renin-containing cells were quantified using an immunoperoxidase technique with an antiserum to human renin. There was a five-fold increase in the number of renin-containing cells in both renal artery stenosis and in untreated, but not in treated, Addison's disease. Peripolar cells were increased in number in three cases of renal artery stenosis, but were unaltered in both treated and untreated Addison's disease. Therefore, neither a reduction in renal perfusion pressure (renal artery stenosis), nor sodium depletion (Addison's disease) consistently affect peripolar cells in humans. These findings do not support the hypothesis that the peripolar cell is part of the juxtaglomerular apparatus. PMID- 1609513 TI - Glomerular tuft ballooning in mitomycin-C-induced renal impairment. AB - Severe ballooning of the glomerular tufts was observed in a 65-year-old man who was treated with mitomycin C (MMC) and had typical MMC-induced renal lesions. He developed renal failure and severe anaemia 6 months after initiation of chemotherapy. Ballooned tufts were caused by enormous expansion of the sub endothelial space simultaneously associated with mesangiolysis. Glomerular cysts, described in a variety of disorders including thrombotic microangiopathy and diabetes mellitus, are derived from cystically dilated and united capillary luminae secondary to mesangiolysis. The morphogenesis of this unusual lesion when induced by MMC differs from that of the glomerular cysts previously reported. PMID- 1609514 TI - Miltenberger subsystem of the MNSs blood group system. Review and outlook. AB - The Miltenberger (Mi) classes represent a group of phenotypes for red cells that carry low frequency antigens associated with the MNSs blood group system. The antigens of this system are known to be located on two sialoglycoproteins denoted as glycophorin A (GP A) and GP B. The structural alterations of seven (classes I, II, III, V, VI, VII, VIII) Mi variants and a related variant (J.L.) have been elucidated. Based on these data and yet incomplete studies of the Mi antigens, the approximate structural alterations in class IV and IX may be predicted. In addition, knowledge of the various structures and partial characterization of the Mi antigens allows one to propose detailed hypotheses concerning the epitopes recognized by the various antibodies that define the Mi subsystem. The understanding of the Mi subsystem at the molecular level paves the way for future studies aimed at a more detailed elucidation of epitopes of Mi-related antibodies, the characterization of novel Mi variants and a search for hypothetical, hitherto unknown Mi-related antibodies. PMID- 1609516 TI - A study of autologous blood collected after joint replacement surgery. AB - Blood from the surgical drains of 11 patients undergoing joint replacement was collected in the Solcotrans Orthopaedic autologous transfusion device and analysed for microparticulate matter before and after micro-aggregate filtration and for its effect on the coagulation of paired venous blood samples. An average of 165 ml (range 0-260 ml) was collected into the Solcotrans during the first hour. Using a Coulter Counter Zm particle counter, particulate matter of diameter 10-20 microns was found in only 2 of 10 collections at an average concentration of 33 x 10(3)/l. All units contained acoagulable blood [kaolin partial thromboplastin time (KPTT) greater than 600 s] but when mixed with paired post operative venous samples exhibited the ability to shorten the KPTT by an average of 4.3 s inspite of the marked dilutional effect of mixing. Retransfusion of blood collected in the Solcotrans Orthopaedic device appears to be a suitable method to supplement or substitute pre-deposit and reduce exposure to homologous blood. Given the low incidence and concentration of microparticles detected, retransfusion of shed blood by this method is unlikely to cause significant pulmonary vascular occlusion resulting directly from deposition of microparticles. PMID- 1609515 TI - Studies in red blood cell preservation. 5. Determining the limiting concentrations of NH4Cl and Na2HPO4 needed to maintain red blood cell ATP during storage. AB - The purpose of the present study was to define the lowest concentrations of ammonium (NH4+) and phosphate (Pi) in an experimental additive solution (EAS) that would support suitable red blood cell (RBC) ATP levels and other in vitro characteristics for at least 84 days. It was determined that ATP maintenance was dependent upon both NH4+ and Pi concentrations. RBCs stored for 84 days in additive solutions containing 10 mM NH4+ and 0, 15, 25 and 40 mM Pi had ATP values averaging 1.87, 2.49, 2.70 and 2.65 mumol/g Hb, respectively. The shedding of exocytic hemoglobin-containing vesicles and percent hemolysis were significantly (p less than 0.001) elevated in the preservative containing 40 mM Pi. These data suggest that an EAS containing 10 mM NH4+ and 15 mM Pi would be optimal for storing RBCs up to 84 days. The extended storage would be particularly advantageous for autologous transfusion programs. PMID- 1609517 TI - Posttransfusion hepatitis in Japan. AB - The incidence of posttransfusion hepatitis and the rate of chronicity were investigated in a program devised at our hospital in December, 1982. Out of 2,596 blood recipients between January, 1982, and December, 1987, 451 (22.7%) developed posttransfusion hepatitis. Seventy-seven patients out of 217 (35.3%) whose course was closely followed progressed to chronicity. The incidence of posttransfusion hepatitis increased with the volume of transfused blood without any evident limitation. Recipients of elevated-ALT donor blood (greater than 26 Karmen units) were found to be more susceptible to posttransfusion hepatitis than those who had received only normal-ALT donor blood. Packed red blood cells, whole blood and fresh whole blood were high-risk components, and fresh frozen plasma a low-risk component of blood. The carrier rate of non-A, non-B hepatitis agents in Japanese healthy blood donors was determined to be 1.2% using the Frost-Reed model of infectious diseases. Anti-hepatitis C virus was detected in 62% of the cases of posttransfusion hepatitis 1 year after transfusion. PMID- 1609518 TI - Haemolytic disease of the newborn probably due to anti-ELO, an antibody to a low frequency red cell antigen. AB - Investigation of mild bilirubinaemia and a positive direct antiglobulin test in a 2 day old baby revealed that the mother's serum contained an antibody against the low frequency antigen ELO, which was present on the father's red cells. Family studies showed that the ELO antigen segregates from Rh, Gc, ADA and PGM1. The ELO antigen is enzyme resistant and therefore not likely to be part of the MNS or Duffy systems. No abnormalities were detected in immunoblotting studies. Although insufficient samples were available to attempt elution of the antibody from the cord cells, it is probable that this case represents the first reported haemolytic disease of the newborn due to anti-ELO. PMID- 1609519 TI - A hemolytic reaction implicating Sda antibody missed by immediate spin crossmatch. AB - Anti-Sda, an antibody not usually considered to cause of hemolytic transfusion reactions, possibly was related to hemolysis following transfusion of red blood cells expressing strong Sda antigen. Prior to transfusion, the antiglobulin antibody screen performed in LISS and an immediate spin crossmatch were negative. Retrospectively, after hemolysis was detected, an antiglobulin crossmatch with red cells from the transfused unit revealed microscopic incompatibility. The transfused unit proved to have strong expression of Sda antigen-facilitating identification of a weak Sda antibody in our patient. In addition, this case represents an unusual instance in which an antibody screen plus an immediate spin crossmatch failed to detect an incompatibility that would have been apparent had an antiglobulin crossmatch been performed. PMID- 1609520 TI - Isoagglutinins following ABO-incompatible bone marrow transplantation. AB - Isoagglutinins were investigated following ABO-incompatible bone marrow transplantation. In major incompatibility anti-A tends to require more time to disappear than anti-B. Correspondingly, A erythrocytes require more time to become demonstrable. There is no such difference in major plus minor incompatibility. In minor incompatibility, isoagglutinins against the recipient blood group may be produced early after bone marrow transplantation, which then give way to a possibly lifelong tolerance for the recipient's old blood group. PMID- 1609522 TI - Comment on 'Red cell alloantibodies in patients with thalassemia' (Spanos et al.) PMID- 1609521 TI - Serological and chemical specificities of twelve monoclonal anti-Lea and anti-Leb antibodies. AB - The serological specificities of twelve hybridomas were compared as to their chemical reactivity as determined using direct binding to synthetic carbohydrate structures. All anti-Lea cross-react with type-1-precursor structures and three different variants of anti-Lea could be defined by their binding to type-3 precursor chains, sialylated compounds and the monosaccharide D-galactose. Three major reactivity patterns were also identified among anti-Leb reagents. Anti-LebL cross-react with Lea and do not significantly bind to H-related structures. Anti LebH,L had both anti-LebL-like activity (cross-reaction with Lea) and anti-LebH like activity (cross-reaction with H). Finally, anti-LebH cross-reacts strongly with H compounds and do not bind to Lea. The binding pattern of anti-LebL suggests that these antibodies have lower affinity for ALeb and BLeb pentasaccharides than anti-LebH. All these specificities are not absolute, but rather are expressed as members of a quantitative progressive varying series, suggesting the existence of a whole range of antibody specificities gradually changing from Lea----Lea,b----LebL----LebH,L----LebH. The results suggest that anti-LebL will always cross-react with Lea and that anti-LebH will always cross react with H related structures. However, under certain well-defined conditions these cross-reactions may not be apparent and antibodies might behave as specific anti-Lea or anti-Leb in certain tests. PMID- 1609523 TI - Insufficiencies of the new WHO western blot criteria in the diagnosis of HIV-1 and HIV-2 infections. PMID- 1609524 TI - [Otitis externa in tropical diving and swimming]. AB - Studies of the microflora of the external auditory canal should help to clarify the frequent acute diffuse external otitis which may occur in recreational scuba divers and swimmers during a stay in the tropics. We found that colonisation with facultatively pathogenic microorganisms increased after exposure. Apart from this contamination, indirect factors such as the tropical climate and intensive exposure to water may play an important role in the aetiology of the external otitis. For individual preventive measures, topical application of paraffin-oil before, and an aqueous solution of alcohol and acetic acid after exposure are recommended. PMID- 1609526 TI - [Analytic, creative and memory processes in hearing and processing of music--a DC potential study]. PMID- 1609525 TI - [Attempt of preventive treatment of striae gravidarum using preventive massage ointment administration]. AB - Striae distensae are an appreciable cosmetic problem for many pregnant women. Preventive application of a water/oil massage cream was tested in a group of 24 gravidae (control group: 26 patients). In the untreated control group striae distensae were observed in two-thirds of the patients, whereas the prophylactically-treated gravidae showed development of striae in only one third of the group given the test preparation. Better results were obtained in women with a favourable constitutional predisposition than in patients with a tendency to overweight. The massage cream was well tolerated by all gravidae. PMID- 1609527 TI - [Importance of the physician-patient relation in patient compliance]. AB - Requestion of compliance or non-compliance is an aspect of patient management which is as old as medicine itself. However, it was long neglected and it is only over the past 15 years that factors having an influence on this important phenomenon have been studied more closely--mostly from the therapist's point of view. The present paper suggests a more comprehensive idea of "compliance". Stress is laid on the importance of communication and cooperation between doctor and patient, because these factors play a major role in the doctor-patient relationship. PMID- 1609528 TI - [Changes in pelvic anatomy in 8 decades--computerized tomography study of obstetrically relevant pelvic measurements]. AB - An increasing proportion of obstetric operative procedures due to cephalopelvic disproportion gave raise to the question, whether there has been a change in pelvic anatomy during the past decades. In a retrospective evaluation of 467 computerized pelvic tomograms of patients aged between 18 and 88 years relevant parameters of pelvic proportion were determined. As these parameters are not subject to age-conditioned changes, the values may be viewed as representative for the time of patients' birth or fertility period respectively. Changes in pelvic anatomy turned out to be complex: The transverse elliptic shape of pelvic inlet changed into sagittal elliptic form, the pelvic midplane is contracted progressively, sacral concavity is reduced. Obviously, this obstetrically adverse development is influenced by the fact, that unfavourable pelvic conformation can be transmitted more intensively by the generous indication for cesarean section. This development is contrasted by the circumstance of fetal acceleration. Therefore, an increase in cephalopelvic disproportion has to be expected. For the sake of a safe obstetrical management in these situations the generous use of ante partum pelvimetric diagnosis seems to be advisable. PMID- 1609529 TI - [Ultrasound diagnosis of fetal lung maturity]. AB - Until now, it has been possible to determine fetal pulmonary maturity only by amniocentesis. Since the functional changes of the fetal lung leading to maturity are also morphologically apparent, pulmonary maturity can be demonstrated sonographically. Obtaining a uniform value for maturity is a problem, since the position of the fetus, the mother's constitution and the instrument setting all influence assessment. The fetal liver was therefore used as a reference organ, since it is subject to the same influences. By frequency analysis of both organs and calculation of the ratio between the frequencies obtained, a mathematical value can be calculated by which pregnancies can be compared and which, as our studies showed, represents a measure of pulmonary maturity. This was documented in 348 patients. It was shown by amniocentesis in 32 patients and the postpartal condition of 25 premature births that a value of 1.11 for this ratio between lung and liver represents the borderline between pulmonary immaturity and maturity. Lower values indicate maturity. If these results are confirmed by further studies on larger groups of patients, it will in future be possible to determine fetal pulmonary maturity very easily and non-invasively. PMID- 1609530 TI - [Vaginal pH self-monitoring by pregnant patients (in comparison with control measurements by the physician)]. AB - Two methods of vaginal pH measurement have been compared. 100 pregnant women measured their vaginal pH by themselves using indicator paper strips and were afterwards controlled apparently by pH electrode. There was no significant difference between both methods, showing that pH indicator strip measurement is sufficiently reliable for pH determination by the pregnant woman herself. PMID- 1609531 TI - [Changes in the basic immunologic parameters interleukin-2 receptor and CD8 antigen in pre-eclampsia]. AB - The serum level of interleukin-2 receptor (sIl-2R) and CD-8 antigen were determined as basic parameter in terms of the stimulation of the t-cell mediated immune reaction in patients suffering from pre-eclampsia (n = 21), HELLP syndrome (n = 12) and pre-existing hypertension (n = 10). The data were compared with those of healthy nonpregnant female volunteers (n = 10) and normotensive pregnant women in the course of pregnancy. Hypertension in pregnancy was associated with an increase of sIl-2R and sCD-8 levels depending on the severity of the hypertensive disorder. In the group of patients with severe pre-eclampsia the median of sIl-2R serum level increased from 370 U/ml (normotensive patients) to 730 U/ml and that of sCD-8 from 640 U/ml to 1100 U/ml. In patients with pre existing hypertension there was a smaller increase of sIl-2R (median 520 U/ml) and decrease of sCD-8 (median 520 U/ml). 6 to 8 weeks after delivery in the group of hypertensive patients the sIl-2R levels were normalized and the levels of sCD 8 were elevated (median 1030 U/ml). The results support the hypothesis of T-cell mediated immunological reactions as pathogenetic factors of the genesis of the hypertensive disorders in pregnancy. PMID- 1609532 TI - [Effect of maternal oxygen inhalation on uterine and fetal circulation in intrauterine retardation and its prognostic value]. AB - In 15 cases of singleton pregnancies with a sonographically supported diagnosis of intra-uterine growth retardation, the effects of maternal oxygen inhalation on uterine and feto-placental circulation have been investigated. For this purpose, the resistance and pulsitility indices (RI and PI) were measured in uterine artery placental site and uterine artery non-placental site, in the umbilical artery, in the descending thoracic aorta and in the median cerebral artery immediately before and after a half-hour oxygen inhalation in each of these IUR pregnancies. The median PI of uterine artery placental site decreased from 0.90 to 0.82 after oxygen inhalation, that of uterine artery non-placental site dropped significantly from 1.26 to 0.75 (p less than 0.05). The number of pathological findings in uterine artery non-placental site was significantly reduced (p less than 0.01). The median RI of the umbilical artery showed a minor decrease. Pathological perfusion in the umbilical artery was not noticeably affected either. The pathological median RI of the descending thoracic aorta was clearly reduced from 1.0 to 0.93. The median RI of the median cerebral artery showed a significant increase from 0.78 to 0.84 (p less than 0.05). The number of pathological findings was reduced by 50%. Compared with only two vessel indices (uterine artery non-placental site, umbilical artery) prior to oxygen inhalation, there was a significant correlation of all vessel indices with subsequent birth weight after oxygen inhalation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609533 TI - [Effectiveness and tolerance of tramadol with or without an antiemetic and pethidine in obstetric analgesia]. AB - The aim of this prospective, randomised, blind study was to investigate the analgesic potency and tolerance of intramuscular Tramadol compared to a standard obstetric analgesia with Pethidine. Triflupromazine was administrated in combination with the two tested analgesics in order to study its efficacy in alleviating the emetic side effects of the tested analgesics. 66 parturients were randomly assigned to three groups: group A: 100 mg Tramadol (Tramal), group B: 100 mg Tramadol (Tramal) and 10 mg Triflupromazine (Psyquil), group C: 50 mg Pethidine (Alodan) and 10 mg Triflupromazine (Psyquil). No significant differences concerning duration of labour, FHR-alterations, umbilical cord blood gases, respiration pattern and Apgar Scores of the neonate occurred. In all three groups the analgesic effect was equally good. Combination of the analgesic with the antiemetic showed no reduction of the incidence and severity of side effects. PMID- 1609534 TI - [Cordocentesis and pH determination sub partu in suspicious cardiotocogram]. AB - Two courses of labor with growth-retarded fetuses are reported, during which cordocentesis was performed because of abnormal fetal heart rate patterns along with a closed cervix. Analysis of umbilical venous blood revealed a normal pH in both cases thus avoiding cesarean section. PMID- 1609535 TI - [Dermal scars on the trunk of a newborn infant--a case of isolated amniotic band syndrome]. AB - We report about a neonate with multiple scars born at our department. The cause of these alterations is the amniotic band disruption complex which will be discussed. This case is of forensic importance because the mother was battered in the 22nd week of gestation. PMID- 1609536 TI - [Pregnancy follow-up of a twin pregnancy with acardius acephalus]. AB - Beginning with the 20th week of gestation a monoamniotic twin pregnancy with acardius acephalus was intensively observed by ultrasound and doppler ultrasound. The acardius only grew until the 24th week of gestation; the fetus underwent a normal development during the entire pregnancy. Doppler ultrasound showed low resistance indices in both umbilical arteries. During the 24th week of gestation the flow in the umbilical artery of the acardius could no longer be registered due to a cessation of development. A normal flow could be registered from the 28th week of gestation until the end of pregnancy in the umbilical artery, aorta fetalis and the art. cerebri med. of the fetus. During the 36th week of gestation the fetus died because of umbilical cord entanglement with the cord of the acardius. PMID- 1609537 TI - [Current therapy of peripheral arterial occlusive diseases in the aged]. AB - The following methods have proven to be effective in the treatment of peripheral vascular disorders in the elderly: local low-dose thrombolysis, systemic fibrinolysis, hemodilution, prostaglandins, transluminal angioplasty, vascular surgery. An early diagnosis, elimination or treatment of risk factors, walking training, and specific treatment in cases of multimorbidity will improve therapeutic effectiveness. PMID- 1609538 TI - [Female sexuality in middle and advanced adulthood]. AB - A study of female sexuality based on 91 interviews with women aged 50 to 91 years (birth-cohorts: 1895 to 1936) is presented. 53% of the interview-partners in this study are sexually active (intercourse: 34%; masturbation: 30%; lesbian sexuality: 1%). 65% report sexual interest. During the past year 58% of the women experienced sexual dreams, 43% sexual fantasies. 26% of the interview-partners had never experienced orgasm. Several age- and cohort-differences are reported. Quotations illustrate the variability of female sexual experiences. PMID- 1609539 TI - [Female sexuality in middle and advanced adulthood: review of previous research]. AB - A comprehensive review of the results of descriptive studies on female sexuality in middle and old age (50 to 100 years) is presented. Central dimensions are "sexual activity", "interest", "enjoyment", and "orgasm". The review integrates studies from several European countries, as well as those conducted throughout the USA. Recent U.S. studies present results which appear to be quite different from the European ones. The former describe their subjects as being considerably more interested in sexuality and more sexually active. Several methodological questions are discussed (sampling, the way of collecting data, neglected variables, and others). PMID- 1609540 TI - [Effect of socioeconomic factors on timing of menopause and the course of climacteric]. AB - The influence of several socioeconomic factors on age at menopause as well as on the mode of climacteric have been investigated in 142 postmenopausal women, originating from Eastern Austria. A significant correlation between socioeconomic factors and the age at menopause could not be observed. Unlike the age at menopause, significant correlations between socioeconomic factors and the degree of severity of climacteric syndrome could be made, resp., the education level, the marital status, total number of children and number of children not living in the parents household correlated significantly with the degree of severity of several symptoms of climacteric syndrome. The socioeconomic factors influenced only the somatic symptoms, which are mainly caused by hormonal changes during the climacteric. According to the results of the present study, psychosocial stress may influence sex hormone levels during the climacteric and postmenopause and, thus, the mode of climacteric. PMID- 1609541 TI - [Cardiovascular diseases in the aged]. PMID- 1609542 TI - [Changes in autonomic cardiovascular control in biological aging--studies using orthostatic provocation and analysis of heart rate profiles in long-term ECG]. AB - We compared the reactions of heart rate in long-term ECG as well as the heart rates and the blood pressures in orthostatic provocation tests using pharmacological blockades in 14 young human subjects aged 19 to 33 years (mean age = 22 +/- 2.2 years) with those of 16 healthy subjects between 67 and 89 years (m = 74 +/- 9.4 years). The blockades were carried out (following the schedule of Jose) first with only propranolol (0.2 mg/kg BW), then propranolol plus atropine (0.04 mg/kg BW), and, finally, only atropine was applied. For the interpretation of the frequency profiles in the long-term ECG prestudies were carried out with dogs, whose high vegetative tension provided us with essential knowledge about the specific type of the autonomous stimulation underlying the respective frequency reaction. Comparing the profiles between old and young human subjects the complete loss of instant reactions in the elderly can be stated. Variations of the heart rate result only from the modulation of the sympathetic stimulation. The "intrinsic heart rate (IHR)" after propranolol plus atropine is still below resting heart rate in the elderly, whereas IHR exceeded the resting heart rate in the younger subjects by nearly 50%. Thus, the basically initial vegetative situation is that, in the younger subjects, their resting heart rates are reached by a permanent parasympathetic slow-down of the IHR, whereas the elderly have to accelerate their slow IHR by permanent sympathetic stimulation in order to reach their "resting" heart rates. The orthostatic provocation tests with the respective blockades prove an age-dependent decrease in the sympathetic system and in the parasympathetic control. A down-regulation of the beta-receptors as a consequence of the permanent sympathetic drive is probable. PMID- 1609543 TI - [Autonomic neuropathy in diabetes mellitus and advanced age]. AB - The reactions of cardiac frequencies of 10 diabetic persons, seven of them dependent on insulin, aged 45.5 +/- 11.8 years, having had diabetes for 12.5 +/- 7.2 years, were investigated with the aid of provocations by a tilting table under selective pharmacological blockades of 1) the parasympathetic system (atropine 0.04 mg/kg body-weight), 2) sympathetic system (propranolol 0.2 mg/kg body-weight), and 3) of both systems (autonomic blockade). These reactions were compared with the reactions of 13 healthy subjects of comparable age (31.6 +/- 9.4 years), as well as with a group of elderly but healthy persons of 74.5 +/- 8.6 years. The well-known age-dependent disturbance of the vegetative control system, characterized by the loss of sympathetic as well as parasympathetic efficiencies, was demonstrated by our study of different ages of subjects. Remarkable was that, in the group of diabetics, in principle, identical patterns of disturbance could be demonstrated in the sympathetic as well as in the parasympathetic systems, but also in the course of cardiac frequency after autonomic blockades. The only difference was that these patterns of disturbance already occur at younger ages. Therefore, one can possibly describe the harmful effect of diabetes on the autonomic nervous system as an acceleration of the process of degeneration, which we also find in connection with "biological aging". PMID- 1609544 TI - [Diastolic left ventricular dysfunction--significance for differential diagnosis and therapy of heart failure in the aged]. AB - The discrimination of the pathogenesis of the clinical picture "heart failure" as caused by a dominant systolic or diastolic LV-dysfunction is of a special importance in the elderly patient because of the consequences for the choice of pharmacological therapy, resulting from the age-related physiological increase of stiffness of the myocardium. The pathophysiology of diastolic dysfunction is characterized by a prolonged relaxation period as well as by compromised passive filling properties, caused by myocardial and external determinants. Typical clinical signs of diastolic dysfunction are dyspnea or pulmonary edema. Cardiac disorders with a dominance of diastolic dysfunction are coronary and hypertensive heart disease as well as hypertrophic or uremic cardiomyopathies. Diagnosis of diastolic dysfunction easily can be performed noninvasively by means of Doppler echocardiography. Pharmacological therapy in diastolic dysfunction should prefer beta blocking drugs and calcium-antagonists against vasodilators or digitalis. PMID- 1609545 TI - Cytokines as immunological adjuvants. AB - Various cytokines have been shown to be effective immunological adjuvants in a variety of model systems, enhancing protection induced by viral, bacterial and parasitic vaccines, and increasing parameters of immunity in tumour immunization models and in clinical trials. While in most cases cytokine adjuvanticity is not as powerful as that shown by the best experimental adjuvants, such as saponin and Freund's, it can rival that of the adjuvants presently allowed for human use and there are many possible routes to improvement. The use of cytokines may allow for a choice of which immune parameters are enhanced in order to further enhance protective effects and decrease the negative effects of vaccines. PMID- 1609546 TI - Canine distemper virus ISCOMs induce protection in harbour seals (Phoca vitulina) against phocid distemper but still allow subsequent infection with phocid distemper virus-1. AB - A candidate canine distemper virus (CDV) ISCOM vaccine has been shown to be effective in protecting harbour seals (Phoca vitulina) from phocid distemper in 1988. However, of the 35 harbour seals receiving this vaccine upon admission to a seal rehabilitation and research centre (Pieterburen, The Netherlands) in 1989, six developed mild inflammatory symptoms of the respiratory tract. Phocid distemper virus-1 (PDV-1) could be isolated from three of these animals. This indicates that the vaccine affords protection from phocid distemper, but may still allow PDV-1 infection of the respiratory tract. Contacts with non vaccinated seals should then be prevented until no more virus is excreted. It is speculated that this PDV-1 infection of the respiratory tract in CDV-ISCOM vaccinated seals is followed by a lifelong immunity. PMID- 1609547 TI - Clinical acceptability and immunogenicity of CVD 908 Salmonella typhi vaccine strain. AB - An attenuated Salmonella typhi strain has been sought as an improved oral typhoid vaccine and as a carrier of protective antigens of other pathogens to make hybrid vaccines. Ideally, such a strain would be safe and induce protective immune responses after a single oral dose. CVD 908 is a mutant of S. typhi wild-type strain Ty2 with recombinant deletions in two genes, aroC and aroD. In phase 1 testing to date, this strain has not produced febrile responses or other significant adverse reactions in adult volunteers given doses of 5 x 10(4) to 5 x 10(7) organisms with sodium bicarbonate. In addition, after just a single oral dose of 5 x 10(7) colony-forming units, this strain induced IgG seroconversion to S. typhi lipopolysaccharide in 83% of vaccinees and stimulated specific IgA secreting gut-derived lymphocytes in 100% of vaccinees. CVD 908 is a new oral typhoid vaccine that should be further investigated as a carrier for expressing foreign antigens in recombinant vaccine constructs. PMID- 1609548 TI - Controlled trial of Haemophilus influenzae type B diphtheria toxoid conjugate combined with diphtheria, tetanus and pertussis vaccines, in 18-month-old children, including comparison of arm versus thigh injection. AB - A randomized, controlled comparison was made in 175 healthy 18-month-old children given either diphtheria and tetanus toxoids and pertussis vaccine, adsorbed (DTP) and haemophilus b diphtheria toxoid conjugate vaccine (PRP/D) concurrently at separate sites (66 children) or a new vaccine combining these products (109 children). Rates of local or systemic adverse effects postimmunization and antibody responses to each component did not differ significantly between groups. DTP-containing vaccines were better tolerated when given in the thigh than in the arm. The combination DTP-PRP/D vaccine performed satisfactorily at 18 months of age, avoiding the inconvenience of two injections. PMID- 1609549 TI - Intranasal immunization with bacterial polysaccharide containing liposomes enhances antigen-specific pulmonary secretory antibody response. AB - Enhancement of bacterial antigen-specific secretory IgA (sIgA) titres in the lungs may enhance resistance to infections, such as pneumonia, occurring at this mucosal surface. To examine this issue, we intranasally administered liposomes containing bacterial polysaccharide antigens from Aerobacter levanicum, Pseudomonas aeruginosa and Streptococcus pneumoniae. In each case, increased titres of bacterial polysaccharide-specific sIgA could be achieved in the lungs following intranasal immunization with antigen encapsulated in liposomes. In comparison with oral immunization, which required high doses of polysaccharide antigen even when coadministered with adjuvant, intranasal administration of liposomes containing polysaccharide antigens achieved a similar pulmonary sIgA response with approximately 1/30 the amount of antigen necessary with oral immunization. In the case of P. aeruginosa, the magnitude of the sIgA response following intranasal immunization was sufficient to significantly reduce mortality from pneumonia produced by this organism. These results demonstrate that liposome-based mucosal immunization strategies can induce increased bacterial polysaccharide antigen-specific sIgA titres in the lung, and reduce susceptibility to pneumonia. PMID- 1609550 TI - Neurovirulence tests of type 3 oral poliovirus vaccine manufactured by Lederle Laboratories, 1964-1988. AB - Oral poliovirus vaccine (OPV) is tested for safety by evaluation of neurovirulence in rhesus and cynomolgus macaques. After intraspinal or intrathalamic injection of varying doses of vaccine, monkeys are followed for 17 21 days, killed, and a histopathological evaluation is made of the severity of poliomyelitis lesions in the spinal cord and brainstem. Each production lot of vaccine is compared with a type 1 OPV reference virus tested by the same method. Records of neurovirulence tests on production lots of type 3 OPV manufactured by Lederle Laboratories, during the period 1964-1988, have recently become available, together with the corresponding tests on type 1 reference vaccine. The cumulative data were collated, using a system under which each monkey was given a single grade according to the severity and spread of neuropathological poliomyelitis lesions. These raw data were assembled into frequency distributions ('neurovirulence profiles'), and used to compare type 3 OPV with the reference vaccine. These comparisons included monkeys injected by intraspinal injection (three vaccine dose levels) and intrathalamic injection (one vaccine dose level), and comprised independent tests conducted by the Food and Drug Administration and by the vaccine manufacturer. A total of 13 different comparisons were made, each one consisting of a pair of profiles, on type 3 OPV and reference vaccine, respectively. In total, these comparisons represented tests on more than 12,000 monkeys. Based on these neurovirulence profiles, the type 3 OPV appeared to be no more virulent than the reference vaccine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609551 TI - Cotton rats previously immunized with a chimeric RSV FG glycoprotein develop enhanced pulmonary pathology when infected with RSV, a phenomenon not encountered following immunization with vaccinia--RSV recombinants or RSV. AB - In studies conducted in the 1960s, children previously immunized with a formalin inactivated respiratory syncytial virus (RSV) vaccine (FI-RSV) developed a greater incidence and severity of pulmonary disease during subsequent natural RSV infection than did controls. It was previously shown that cotton rats immunized with FI-RSV or immunoaffinity-purified fusion (F) glycoprotein developed enhanced pulmonary histopathology following intranasal challenge with RSV. In the present studies, various forms of immunization, including parenteral inoculation of an immunoaffinity-purified F glycoprotein or a chimeric FG glycoprotein produced in insect cells using a baculovirus vector (Bac-FG), intradermal infection with a vaccinia-F recombinant (Vac-F) or intranasal infection with an adenovirus-F recombinant (Ad-F) or RSV, were compared for immunogenicity, efficacy and ability to alter the host so that enhanced pulmonary histopathology developed during RSV infection 3 months after immunization. Immunization of cotton rats with F glycoprotein, Bac-FG, Vac-F, Ad-F or infection with RSV induced high levels of ELISA-F antibodies, but the antibodies induced by purified F glycoprotein of Bac FG had low levels of neutralizing activity. Immunization with Vac-F or Ad-F, or infection with RSV induced a high level of resistance to pulmonary RSV replication, whereas animals immunized with Bac-FG or FI-RSV were only partially protected. Following RSV challenge, animals immunized with purified F glycoprotein or Bac-FG developed the highest levels of bronchiolar and alveolar histopathology, those immunized with FI-RSV had intermediate levels, and those immunized with Vac-F or RSV had histopathology scores at control levels. Ad-F immunized animals had elevated scores of bronchiolar but not alveolar histopathology; however, this finding was not reproducible. Passive transfer of pooled immune sera from animals infected with RSV or Vac-F and Vac-G was highly protective, whereas pooled sera from animals immunized with Bac-FG failed to protect the lungs against RSV challenge. Increased pulmonary histopathology was not observed in the passively immunized animals following RSV challenge, suggesting that the histopathology was mediated by RSV-specific T cells. These data indicate that subunit F glycoprotein or chimeric FG vaccines share with FI RSV the properties of (i) induction of F antibodies with low neutralizing activity and (ii) enhancement of pulmonary histopathology during subsequent RSV infection. These observations confirm the need for caution in studies involving the administration of RSV subunit vaccines to seronegative humans. PMID- 1609552 TI - [The detection of Alternaria mycotoxins in laboratory culture]. AB - Analytical methods are described for detection of the Alternaria mycotoxins alternariol (AOH), alternariol monomethyl ether (AME), altenuene (ALT) and tenuazonic acid (TeA) in natural and semisynthetic laboratory cultures. After extraction and purification of the crude extract by column chromatography on silica gel the qualitative and quantitative analyses were carried out by thin layer (TLC)- and high performance liquid chromatography (HPLC). HPLC separations were achieved using a Hypersil ODS column with methanol/water containing a complexing agent as eluent. Detection at 340 nm (AOH, AME, ALT) and 280 nm (TeA), respectively, has proved to be favourably. AME and TeA were produced in high purity and high yields as standard substances by two Alternaria strains. The identity of the toxins could be confirmed by EI-, CI- and FAB-mass spectrometry. PMID- 1609554 TI - Fungistatic action of natural oils and fatty acids on dermatophytic and saprophytic fungi. AB - Testing the inhibitory effects of some natural oils and fatty acids on growth of some of the dermatophytes revealed the high fungistatic effects of clove and peppermint oils. These oils when applied at 1% concentration with 1% tween 80 inhibited growth of the tested fungi seriously. Fatty acids were relatively uneffective and the possibility of including clove and peppermint oils in antidermatophytic drugs were suggested. PMID- 1609553 TI - [Toxin-producing ability of molds of the genus Alternaria]. AB - The ability to produce the Alternaria mycotoxins alternariol (AOH), alternariol monomethyl ether (AME) and altenuene (ALT) were studied on 87 Alternaria strains. 50 isolates were studied to produce tenuazonic acid (TeA). The strains were isolated from CCM-maize and stored hay. They were cultured under optimum conditions and analysed by various chromatographic methods for the 4 mycotoxins. All Alternaria strains studied produced AME and TeA, 77 per cent also AOH. A production of ALT was detected only in 18 per cent of the isolates. The concentrations of toxins produced were 0.08-482 (162) ppm for AME, 0.05-1862 (121) ppm for AOH, 0.1-34 (9.1) ppm for ALT and 0.02-42 (11.3) mg/100 ml liquid medium for TeA. The species Alternaria alternata (Fries) Keissler and Alternaria tenuissima (Kunze:Fr.) Wiltshire produced the greatest amounts of all mycotoxins studied. PMID- 1609555 TI - [The occurrence of aeromonads in a drinking water supply system]. AB - This study concerns with the occurrence of aeromonads, coliforms and colony counts in a drinking water supply. Aeromonas contents were detected in the range of 15.0 to greater than 2,400/100 ml in the raw water samples of the man made lake. After the drinking water treatment process including fast sand filtration and chlorination aeromonads indicated in comparison to total coliforms and colony counts early and significant an after-growth of maximal 240 aeromonads/100 ml in the peripheric drinking water supply. Drinking water samples characterized by a higher water temperature resulted in the highest contents of aeromonads. The Aeromonas-Species Aeromonas sobria and Aeromonas hydrophila were isolated most frequently with 56.9 and 37.4 percent, respectively. The role of aeromonads as an indicator of after-growth in drinking water supplies is discussed. PMID- 1609557 TI - Independent nursing practice? PMID- 1609556 TI - Physiological study on riboflavin production by hydrocarbon-utilizing Candida guilliermondii Wickerham. AB - The production of riboflavin (vitamin B2) by Candida guilliermondii Wickerham cultivated on solar-containing medium was stimulated in the presence of corn oil (0.1 g%), arginine, phenylalanine (1 m mole/l) or CoSO4.7H2O (1000 micrograms/l). On the other hand, emulsifying agents strongly inhibited yeast growth and vitamin production. Similarly, FeSO4.7H2O and MnSO4.4H2O at 50 and 200 micrograms/l levels, respectively, also showed inhibitory effect. Among the tested purines, xanthine enhanced vitamin production. PMID- 1609558 TI - Recognition and prevention of fetal alcohol syndrome. PMID- 1609559 TI - An open letter to Steven West--(midwifery). PMID- 1609560 TI - An open letter re: Midwifery Services Review Committee Report. PMID- 1609561 TI - Dr. Patricia Donahue. Interview by Eve Henderson. PMID- 1609562 TI - Visual impairment in Nordic children. I. Nordic registers and prevalence data. AB - A Nordic study group of ophthalmologists, NORDSYN, has compiled data from registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children. Each record contains the following information: sex, year of birth, year of registration, classification of visual impairment, ocular diagnosis, systemic diagnosis, aetiology and evt. additional impairments. The ocular diagnoses were compiled into groups, and coding systems for aetiology and additional impairment were developed. The sex distribution revealed a dominance of males compared to the general population at the same age. Cases with non genetic aetiology showed--through to a lesser extent--the same relative preponderance of males. The diseases in males caused by x-linked genetic factors do, therefore, not fully explain the sex distribution observed in the study. The national prevalences for registration of childhood blindness (WHO-definition: best corrected visual acuity in the best eye less than 3/60 or visual field less than 10 degrees around fixation for the ages 0-15 years) are per 100,000 child population aged 0-15 years: Denmark 41, Finland 15, Iceland 19 and Norway 15. The differences are primarily presumed to be due to varying efficiency in registration. The proportion of visually impaired children with an additional mobility, hearing or mental impairment is between one-third and one-half of the national materials, thus indicating the need for interdisciplinary tracing of and care for the visually impaired child. This study documents the need of uniform routines for data classification of visually impaired children. The quality of the data in the present study calls for caution in the interpretation of the prevalence estimates. Incidence studies are being prepared to obtain information on whether the amount and causes of visual impairment in children with or without multiple impairments are changing. PMID- 1609563 TI - Visual impairment in Nordic children. II. Aetiological factors. AB - Careful clinical-aetiological assessment of visually impaired children is one of the prerequisites for prevention of future, 'unavoidable' cases of visual impairment of children in the industrialized part of the world. In a collaborative study (NORDSYN) between four Nordic national registers of visual impairment, we analysed and classified some of the factors considered to be essential components for the development of low vision or blindness in children. We discuss the conceptual basis for aetiological classification of eye disorders and visual impairment. An aetiological classification system, based on the type and debut of an essential causal factor is introduced. We present data on 2527 visually impaired children from the Nordic countries. In accordance with several other reports from the last twenty years it is demonstrated that prenatal factors, including genetic aetiologies, were involved in a large proportion (66%) of the cases. In children without additional impairments the corresponding fraction was 74%. Genetic factors accounted for a little over half of the prenatal cases, and in a substantial number of children (40%) with visual impairments of prenatal origin, the causes were obscure. In 1/5 of the material some peri-neonatal causal or modifying factor was identified. In 7% only, the presumed aetiological factor was introduced in the infantile-juvenile period of life. Further prevention of visual impairment among children of the industrialized countries would benefit most from a more comprehensive understanding of prenatal, nongenetic causal factors, further knowledge about regulating mechanisms responsible for gene expression, and additional improvements in perinatal care. PMID- 1609564 TI - A population survey of retinitis pigmentosa and allied disorders in Denmark. Completeness of registration and quality of data. AB - The aim of this study was a complete survey of all patients in Denmark with a diagnosis of retinitis pigmentosa. The study was performed during the period 1986 1989 and included all persons living in Denmark from 1850 to 1989. We describe the methods of registration from medical and non-medical sources, based on defined criteria. The inclusion criteria were fulfilled by 1890 persons, 1056 males and 834 females. Evaluation of this 'Danish Retinitis Pigmentosa Register' demonstrates an overall completeness of about 80%, increasing from 40% for birth cohorts before 1911 to 90% for patients born since 1981. Concerning diagnostic confidence, 73% of the probands were characterized as certain, 16% as probable, and 11% as possible. Non-systemic cases comprised 61% of all probands and 31% had systemic disease, the rest being unclassified with respect to systemic involvement. The material is considered very suitable for epidemiological treatment and continuous clinical and genetic investigations. PMID- 1609565 TI - Prevalence of retinitis pigmentosa and allied disorders in Denmark. I Main results. AB - In a nation-wide study we utilized all available sources to characterize the prevalence rates of retinitis pigmentosa. 1301 persons, 715 males and 586 females, were identified, with a diagnosis of retinitis pigmentosa or some other tapetoretinal dystrophy, and living in Denmark per January 1, 1988. The corresponding completeness corrected prevalence rate of retinitis pigmentosa was 1:3026. All cases were classified as 'certain', 'probable', or 'possible'. The age specific prevalence rates increased until 40-50 years, reaching a level of 35 40 male cases per 100,000 and 25-30 female cases per 100,000. Age specific prevalence rates were standardized to the WHO World Standard Population and compared to rates reported from Britain and The United States. World standardized prevalence rate for males was 25.29 per 100,000 and for females 19.31 per 100,000. The preponderance of males was highly statistically significant, (P less than 0.01). PMID- 1609567 TI - The postnatal development of the oscillatory potentials of the electroretinogram. IV. Mesopic characteristics. AB - The postnatal development of the oscillatory potentials (OP) of the rat's electroretinogram (ERG) was studied during relatively mesopic adaptational conditions. The behaviour of the OPs induced at an interstimulus interval (ISI) of 30 sec entailed photopic qualities at an individual level, but when summated conformed to a scotopic course of postnatal maturation. An ISI of 1 min elicited OPs with individual scotopic characteristics. The total oscillatory activity culminated at 17 days of age at both ISIs, similar to more scotopically induced oscillations. These results show that relatively mesopic states of adaptation do not promote any earlier appearance of the OPs, and that the immature mesopically induced OPs seem to contain both scotopic and photopic qualities reflecting a postnatal change of balance between these components. Furthermore, photopic mechanisms seem to govern the oscillatory activity in the mature rat retina. We suggest that the differences in relation to adaptational conditions between the immature and mature OPs may reflect the postnatal status of the dopamine and its synthetizing enzyme, tyrosine-hydroxylase. PMID- 1609566 TI - Photopic ERG components in retinitis pigmentosa. AB - The persistence of a residual flicker electroretinogram 20 Hz response in many cases of retinitis pigmentosa, when the Oscillatory Potentials (OPs) were no longer recordable, led the authors to an investigation by Fourier analysis. The study was carried out in 33 patients affected by different hereditary forms of retinitis pigmentosa revealing recordable 20 Hz flash ERG responses. We applied the Fourier analysis to this ERG response and compared the weight percentage of the first two components to the OP added amplitude. The analysis showed that the 20 Hz flash ERG response contains only the first harmonic in patients with no recordable OPs and both harmonics in patients with recordable OPs. This relationship between OPs and 20 Hz second component, that is possibly related to the activity of inner retina as well as the OPs, can demonstrate an alteration of the inner retina which evolves with distinct electrophysiological features from the ERG photoreceptor impairment. PMID- 1609568 TI - Quantitative assessment of aqueous flare and aqueous 'cells' in pseudoexfoliation syndrome. AB - We used the laser flare-cell meter to measure aqueous flare and aqueous 'cells' in 38 eyes of 38 patients with pseudoexfoliation, in 36 normal control eyes of 36 subjects, and in 19 eyes of 19 patients with chronic open-angle glaucoma unrelated to pseudoexfoliation. In pseudoexfoliation eyes, both aqueous flare (0.61 +/- 0.55 mg/ml human albumin equivalent) and aqueous 'cells' (mean 10.70, range 0-50.6 cells/0.075 mm3) were significantly higher than in the normal control group (flare 0.15 +/- 0.06 mg/ml, 'cells' 0.43, range 0-2, P less than 0.0001) and in the glaucoma group without pseudoexfoliation (flare 0.19 +/- 0.08 mg/ml, 'cells' 0.80, range 0-2.4, P less than 0.0001 and P less than 0.005). No significant difference could be found between the flare and cell counts of normal eyes and glaucoma eyes without pseudoexfoliation (P greater than 0.09, P greater than 0.05) and between PSX eyes with (18 eyes) and without (20 eyes) open-angle glaucoma (P greater than 0.99, P greater than 0.4). Our findings indicate that the blood-aqueous barrier is impaired in eyes with pseudoexfoliation, and that the laser flare-cell meter may be a useful tool to quantify these changes. These alterations of the blood-aqueous barrier need to be considered in medical therapy and intraocular surgery. PMID- 1609569 TI - The frequency of pseudoexfoliation syndrome in the eastern Mediterranean area of Turkey. AB - In this study we evaluated the frequency of pseudoexfoliation syndrome, the percentages of glaucoma and senile cataract in patients with and without pseudoexfoliation syndrome, and the percentages of pseudoexfoliation syndrome in patients with glaucoma and senile cataract in the Eastern Mediterranean area of Turkey. We examined 1356 persons over 40 years of age. Frequency of pseudoexfoliation syndrome in the greater than or equal to 50 years old age band was 7.2%, and there was a statistically significant difference between the sexes. Over 60 years of age, the frequency of pseudoexfoliation syndrome was 11.2%, the percentage of glaucoma in patients with pseudoexfoliation syndrome was 34.3%, the percentage of pseudoexfoliation syndrome in patients with glaucoma was 46.9%, the percentage of cataract in persons with pseudoexfoliation syndrome was 88.1%, and the percentage of pseudoexfoliation syndrome in persons with cataract was 17.7%. The differences between the percentage of glaucoma and cataract in patients with and without pseudoexfoliation syndrome, were both statistically significant (p less than 0.001). PMID- 1609570 TI - Clinical features of capsular glaucoma in comparison with primary open-angle glaucoma in Japan. AB - Clinical features of capsular glaucoma during a recent 15-year period were compared with those of primary open-angle glaucoma (POAG). Out of 1623 new glaucoma patients, 263 patients (16.2%) were capsular glaucoma and 268 (16.5%) were POAG. The patients with capsular glaucoma were older than the patients with POAG. The former had higher intraocular pressure, lower visual acuity, more advanced visual field change and heavier trabecular pigmentation than POAG patients at the time of initial examination. These findings suggest that capsular glaucoma is more difficult to manage than POAG and that the prognosis is poorer than for POAG. Pseudoexfoliative material was found on the pupillary border in 98.3%, on the central lens surface in 46.1%, and on the peripheral lens surface in 72.3%. Though 190 of 263 patients with capsular glaucoma (73.9%) were unilateral cases, 38.9% of the fellow eyes had some abnormalities related to glaucoma. Phakodonesis was found in 10% of patients with capsular glaucoma. This finding suggests that the presence of capsular glaucoma might be a risk factor in cataract surgery. PMID- 1609571 TI - Trabeculectomy at the inferior limbus. AB - Fourteen eyes (12 with open-angle glaucoma and 2 with secondary glaucoma) of 14 patients were operated by trabeculectomy at the inferior limbus. The surgical technique is described and results of 6-12 months follow-up are reported. Complication rate was reasonably low. Early postoperative IOP higher than 30 mmHg occurred in one eye where a blood clot and sodium hyaluronate obstructed filtration of aqueous. Postoperative mean IOP was 16.3 mmHg (6-29 mmHg) in 13 eyes at 3 months, 17.1 mmHg (13-26 mmHg) in 12 eyes at 6 months and 20.1 mmHg (11 31 mmHg) in 12 eyes at 12-16 months. Three eyes had follow-up of 19-21 months and corresponding IOPs were 14, 15 and 22 mmHg. IOP was less than 22 mmHg in 10/12 eyes at 6 months and in 8/12 eyes at 12-16 months. 6/12 eyes managed without medication at 6 months and 2/12 eyes at 12-16 months. Trabeculectomy at inferior limbus is a safe procedure and it is recommended as a surgical procedure in eyes after previous cataract surgery. PMID- 1609572 TI - Side effects of topical treatment in pigmentary glaucoma. AB - A series of 35 patients with pigmentary glaucoma were asked to report possible side effects of topical glaucoma medication using a multiple-choice questionnaire. Of the 31 patients (89%) returning the forms, 22 (71%) were men and 9 (29%) women with a mean age of 45.1 years, range 23 to 72 years. The mean follow-up time of their glaucoma was 10.7 years, range 2 to 30 years. A mild burning feeling (in 50% in all treatment groups) and redness of the eyes (in 42% treated with timolol alone and in 50% with timolol combined with dipivephrine, pilocarpine or both) were the main complaints, followed by a slight reduction of vision (in 17% in the timolol group and in 56% with combined treatment) and mild watering of the eyes (in 42% of the timolol and in 31% of the combined treatment groups). Twenty-three percent of the patients did not have any side effects from their topical medication. Patients who admitted defaulting their topical treatment once a month amounted to 43% and once a week to 17%. Patients who admitted to never having missed a drop amounted to 40% of the sample; forgetfulness and haste were the main reasons for not applying the drops. PMID- 1609573 TI - Non-stereo photographic screening in long-term follow-up for detection of proliferative diabetic retinopathy. AB - The efficiency of two non-stereo photographs of the posterior pole as a screening device in long-term follow-up for the detection of proliferative diabetic retinopathy was evaluated in a clinical setting among 1341 diabetic hospital patients. False positive findings occurred in 0.4% (6/1341). Severe irreversible sight-threatening complications from undetected proliferative diabetic retinopathy, such as retinal traction detachment or secondary glaucoma, never occurred. Vitreous haemorrhages due to missed new vessels in the photographic area occurred in only 2 out of 3020 photographic reading sessions over a 5.5 year period. Evaluation of the nature, localization and magnitude of new vessels showed that optic disc new vessels were generally over-diagnosed in younger patients and missed in patients aged 45 years or older. New vessels elsewhere were more frequently misdiagnosed in patients older than 50 years. New vessels were most commonly found on the temporal arcades (48%) of the eyes and nasal to the optic disc (42%) but were significantly rare beyond the posterior pole (13%) (P less than 0.001). Patients younger than 60 years had significantly more lesions (P less than 0.001) and these lesions tended to be bilateral. Two non stereo photographs of the posterior pole is a safe and efficient alternative method to conventional survey for proliferative diabetic retinopathy. New vessels are significantly most common in the posterior pole and complications from new vessels occurring exclusively outside the posterior pole can be disregarded. Bilateral neovascularization should be anticipated in patients under 60 years. PMID- 1609574 TI - Macular recovery time, diabetic retinopathy, and clinical variables after 7 years of improved glycemic control. AB - Effects of long-term improved glucose control on neurosensory retinal function are investigated. Changes in macular recovery of nyctometry (photostress) are assessed in 45 insulin-dependent diabetic patients between study start and after 7 years prospective follow-up (the Oslo Study). Intensified insulin treatment improved glycosylated hemoglobin (HbA1) from 11.7 +/- 2.2% at start to a 7-year cumulative mean of 9.5 +/- 1.5% (p less than 0.0001). Improved macular recovery performance was observed in patients with 7-year mean HbA1 below 10%, compared to a worsening in those above 10% (p less than 0.001-0.02), and non-proliferative retinopathy progressed less in those with HbA1 below 10%, than in those above (p less than 0.01). Macular recovery at study start did not predict progression or outcome of retinopathy 7 years later. Intraocular pressure fell during the 7 years (p less than 0.001) and was cross-sectionally negatively correlated to macular recovery at the 7-year end-point (p less than 0.001-0.002). Macular recovery was not related to age, duration of diabetes, systemic blood pressure, or urinary albumin excretion level. The study indicates that severity of retinopathy, glycemic control and intraocular pressure are interesting covariants to neurosensory dysfunction in diabetes. Furthermore, the study suggests a critical level of long-term blood glucose or retinopathy, or both, above which neurosensory function of macular recovery is significantly reduced. PMID- 1609575 TI - White spots in the central fundus in diabetic children and adolescents. AB - Previously, small defects in the retinal pigment epithelium appearing as depigmented spots in the fundus photographs have been observed in a high proportion of adult diabetic patients. In order to evaluate whether these changes already occur in children we examined the black-and-white and colour fundus photographs of 206 diabetic children aged 4.6-19.6 years (median 12.6), with the median duration of diabetes of 4.7 years (range 0.0-14.2). Early signs of retinopathy were observed in 27 (13.1%) of them. The control group was composed of 45 healthy children aged 8.1-16.6 years (median 11.8). One or more tiny white spots in the fundus of one or both eyes were observed in 97 diabetics (47.1%), more often in those with retinopathy than in those without (66.7% vs. 44.1%, p less than 0.001). In the control group similar spots were observed in 24 children (53.5%). Only in a small proportion of children (4.4% of both diabetic and control patients) were the spots numerous. In children most of the white spots in the fundus may represent drusen type deposits rather than defects in the pigment epithelium. PMID- 1609576 TI - Normal variations of the posterior corneal surface. AB - Measurements of the sphero-cylindrical components of the rear corneal surface were taken from 80 healthy right eyes in order to determine normal variations. Dimensions of this surface were strongly influenced by the front corneal surface with the exception that the rear surface exhibited more toricity. Both surfaces tended to be flatter in males compared to females and in myopes compared to hyperopes. The corneal surfaces were also found to be flatter in younger eyes compared to older eyes, but this finding was most likely due to the preponderance of myopes in the young and hyperopes in the older group. The influence of the ratio of anterior: posterior corneal surface radius upon the estimation of total corneal power as required for intraocular lens implant calculations was also considered. PMID- 1609577 TI - Ptosis following periocular or general anaesthesia in cataract surgery. AB - The incidence and duration of postoperative ptosis was investigated in 64 patients undergoing cataract surgery. Thirty-two patients had a 2-point periocular regional anaesthesia while 32 others were given general anaesthesia. The palpebral aperture and the levator muscle function were measured preoperatively and then on the 1st, 2nd, 4th and 7th postoperative days or as long as ptosis persisted. On the 1st postoperative day, about half of the patients in both groups demonstrated ptosis. On the 2nd day, ptosis was more common in the general anaesthesia group. The ptosis persisted 1 week postoperatively in 2 patients, both belonging to the general anaesthesia group. It is concluded that postoperative ptosis is common both after local and general anaesthesia. In most cases it is shortlasting and may be related to the volume or myotoxicity of a local anaesthetic drug. The use of a superior rectus muscle bridle suture and/or lid speculum may be important in provoking ptosis of longer duration. PMID- 1609578 TI - The IOP-IOL. A probe into the eye. AB - The intraocular lens (IOL) implant can be looked upon as a probe into the space of the eye. Adapting that view, it is logical to furnish the IOL-probe with biomedical sensors that would explore its environment. A sensor is presented for continuous monitoring of intraocular pressure (IOP), incorporated in the haptics of an IOL. The sensor consists of a capacitative spiral circuit, needing no energy, correlating its resonance frequency to the actual IOP. This resonance frequency is remotely and non-invasively detected by an external device located in a spectacle frame. PMID- 1609579 TI - Pollution keratoconjunctivitis. A review. AB - In 'sick building syndrome' and other questionable environmental conditions, it is important to consider eye troubles. This review deals with several objective methods relevant for pollution keratoconjunctivitis. A hypothesis is put forward: A reduced lipid layer of the tear film causes reduced break-up time, increased vital staining and increased number of cells in the conjunctival fluid. PMID- 1609580 TI - Bilateral branch vein occlusion. AB - Bilateral branch retinal vein occlusion is a relatively rare occurrence. We report 4 patients who presented with bilateral branch retinal vein occlusion and in each of these cases the fellow eyes were involved within 6 months of the initial episode. The patients were relatively young and all of them had associated essential hypertension. The patients maintained a relatively good visual acuity through a 6-months to 1-year follow-up. This report highlights this rare entity, the associated risk factors and visual prognosis. PMID- 1609581 TI - Central retinal artery occlusion in a patient with Marfan's syndrome. AB - A case of central retinal artery occlusion in a patient with Marfan's syndrome secondary to possible thromboembolism from a prolapsed mitral valve is presented. Clinical investigations and treatment of this condition are discussed. The world literature on retinal occlusive events secondary to mitral valve prolapse is briefly summarised. To the best of our knowledge, this is the first case report in the literature of central retinal artery occlusion in a patient with Marfan's syndrome. PMID- 1609582 TI - Congenital glaucoma resulting from a chromosomal translocation. AB - A boy with congenital glaucoma, mental retardation and dysmorphic features is described. Chromosome analyses revealed two different, apparently balanced translocations; between the long arms of chromosomes 2 and 10 as well as between the long arms of chromosomes 8 and 12; 46,XY t(2;10)(q33;q26)pat, t(8;12) (q24;q21). The healthy father of the patient had the same balanced translocation between the long arms of chromosomes 2 and 10; 46,XY, t(2;10)(q33;q26). PMID- 1609583 TI - What price progress? Failed innovations of the knee prosthesis. PMID- 1609584 TI - Polyethylene wear in unicondylar knee prostheses. 106 retrieved Marmor, PCA, and St Georg tibial components compared. AB - 106 unicondylar knee replacement tibial components were retrieved and analyzed for the amount and type of polyethylene wear. Three different designs were retrieved which had essentially the same femorotibial conformity. Each design showed a characteristic failure pattern. The polyethylene of PCA tibial components showed serious delamination after only short durations, as a result of heat pressing. St Georg sledge prostheses showed some delamination after 4 years' duration due to sub-surface cracks which were initiated by fusion defects in the polyethylene; metal backing of the components did not affect delamination of this prosthesis. The Marmor designs showed the least wear, with shiny depressions and surface pitting; no delamination was observed in the Marmor prosthesis. Molecular weight determination by gel permeation chromatography and analysis of crystallinity using Fourier transformation infra-red spectroscopy demonstrated that St George polyethylene had higher molecular weight and crystallinity than Marmor polyethylene. In some of the components investigated, crystallinity and molecular weight of the polyethylene were reduced under the wear track when compared with the unworn polyethylene. Since fusion defects may cause delamination of polyethylene we urge manufacturers to reduce the number of such defects. PMID- 1609586 TI - Polyethylene wear of the PCA unicompartmental knee. Prospective 5 (4-8) year study of 120 arthrosis knees. AB - In Lund, 120 arthrosis knees had the PCA unicompartmental endoprosthesis during 1983-1987 and were followed prospectively for 5 (4-8) years. 17 knees were excluded from the final clinical follow-up because of the development of rheumatoid arthritis (2), severe neurologic disease (3), or death (12). Subjectively, 68 knees were much improved, 26 improved and 9 had failed. First steps problems were only present in the uncemented group of 49 knees. Of the 9 failures (7 cemented and 2 uncemented) 6 were revised. The main reason for revision was loosening of the femoral component (2), tibial component (2), or both components (1), and polyethylene wear (1). However, all revised tibial components showed polyethylene wear, in 4 quite pronounced. Weight-bearing radiographs (61 knees) revealed major polyethylene wear in an additional 14 knees; not only in thin tibial components. There may be an increasing clinical problem due to polyethylene wear. With the presented findings the PCA unicompartmental knee endoprosthesis cannot be recommended. PMID- 1609585 TI - Multicenter study of unicompartmental knee revision. PCA, Marmor, and St Georg compared in 3,777 cases of arthrosis. AB - The prospective Swedish Knee Arthroplasty Project contained 772 PCA, 1564 Marmor and 1441 St Georg unicompartment prostheses, implanted for gonarthrosis during the period December 1983-July 1990. Follow-up was performed in September 1991. There was a significant difference in the cumulative revision rate after only 2 years, increasing to 15 percent for the PCA, compared with 5-7 percent for the two other types. The difference between PCA and Marmor/St Georg was loosening of the femoral component. Major polyethylene wear was noted in a quarter of the revised PCA tibial components. The wear pattern of Marmor/St Georg was not analyzed in this study. PMID- 1609587 TI - Polyethylene delamination in the PCA total knee. Material analysis in two failed cases. AB - Two patients had severe polyethylene-wear synovitis after total knee arthroplasty for arthrosis. Full-leg length weight-bearing radiographs were diagnostic. The polyethylene of the tibial components showed excessive delamination. The morphology and crystallinity of the polyethylene showed that surface treatment of the material could well be held responsible for the massive wear. PMID- 1609588 TI - Strain, stress and stretch of peripheral nerve. Rabbit experiments in vitro and in vivo. AB - Mechanical stretching is known to cause morphologic and functional changes in peripheral nerve. The points at which these changes occur, however, are not clearly defined and reported data are conflicting. The studies presented in this paper provide a basic understanding of the biomechanical properties, stretch injury patterns, and changes of conduction properties of peripheral nerves due to stretching. Our studies showed that peripheral nerves exhibited non-linear stress strain characteristics when placed under tension. Initially, under tension, the nerve had a low modulus that increased gradually with increasing strain until reaching a maximal value. When the nerve failed under tension, the perineurium inside the nerve ruptured, but the exterior of the nerve remained intact. Our results also show that a peripheral nerve in situ was under significant strain, but minimal in situ stress (less than 0.05 MPa). The in situ strain might vary with limb position, but did not appear to exceed the limit beyond which substantial tension or stress would be developed in the nerve. The time-dependent viscoelastic behavior of peripheral nerves were also characterized. The maintenance of small in situ stresses suggests that sustained increases in tension could be adversely affecting the electrophysiologic properties of the nerve. Indeed, marked alteration of conduction properties resulted from even a small stretch of 6 percent beyond the in situ length of the nerve, or stress less than 10 percent of the ultimate strength of the nerve. PMID- 1609589 TI - The Spitzy shelf operation for the dysplastic hip. Retrospective 10 (5-25) year study of 124 cases. AB - Since 1961 we have used the Spitzy shelf operation combined with a vertical flap osteotomy of the outer cortex of the ilium for early arthrosis secondary to acetabular dysplasia, subluxation, and dislocation. In 124 hips, followed for 10 (5-25) years, clinical improvement was maintained in 67/85 of patients who were operated on under the age of 30 and in 22/39 of patients treated after 30. However, less than half of the hips in the younger group and only one out of ten in the older group were symptom-free. PMID- 1609590 TI - The acetabular opening angle in Perthes' disease. Radiographic study of 62 unilateral cases. AB - Pelvis AP radiographs in 62 patients with unilateral Perthes' disease were studied in search of changes of the acetabulum throughout the active stages of this disease. The length of the acetabular roof, the diameter of the acetabulum, and the opening angle of the acetabulum, were compared with the contralateral hip. The length of the acetabular roof did not change, but the opening angle and the diameter of the acetabulum increased. This increase began in the earliest stage of the disease in half of the cases; it reached a maximum during the resorptive and the reconstructive stages, then it decreased to reach normal values at skeletal maturity. These changes were related to the extent of the epiphyseal necrosis. Probable causes were local hyperemia and a mechanical adaptation of the acetabulum to a cartilaginous coxa magna. The opening angle has a prognostic value and influences our choice of therapy. PMID- 1609591 TI - Femoral neck fracture fixation with hook-pins. 2-year results and learning curve in 626 prospective cases. AB - We performed a prospective 2-year follow-up study of 626 consecutive femoral neck fractures treated with closed reduction and hook-pin fixation in all cases. The woman:man ratio was 2.9:1, the displaced:undisplaced fracture ratio 2.6:1. Mean patient age was 78 (18-100) years. The first 476 fractures were operated on by one of six surgeons with special interest in the technique, while the remaining operations were performed by any of the 35 surgeons in the department, all specialists in orthopedic surgery. Mortality within two years was 31 percent. Healing complications (redisplacement, nonunion or segmental femoral head collapse) in the total material/survivors only were for undisplaced fractures 5/7 percent, for displaced fractures 30/41 percent and for the total material 23/32 percent. According to life-table analysis, the complication rate in the total material at two years was 24 percent. The rate of secondary arthroplasty for healing complications was 13/19 percent. For displaced fractures, as well as for the total material, the group of specially interested surgeons had better results than the department as a whole. PMID- 1609592 TI - Internal fixation of femoral neck fractures. Dynamic Hip and Gouffon screws compared in 73 patients. AB - A prospective, randomized study comparing the Dynamic Hip screws and the Gouffon screws in the treatment of femoral neck fractures was terminated before the planned number of patients had been admitted, owing to a preponderance of early failure of the Gouffon screws (P 0.014); thus only 73 patients entered the study. After three years' follow-up, 25/38 Gouffon screws and 12/35 Dynamic Hip screws had failed. Six patients treated with Gouffon screws and 14 treated with Dynamic Hip screws had died. The outcome still favoured the use of Dynamic Hip screws (P 0.02). PMID- 1609593 TI - Years of potential life lost after hip fracture among postmenopausal women. AB - From January 1987 and onwards all cases of hip fracture in Arhus County, Denmark, were registered in a prospective multicenter investigation. Until December 1990, 2273 postmenopausal women (greater than 50 years) with first hip fractures were registered. Of these 643 sustained a hip fracture in 1988. Life tables were constructed for different age groups; the excess mortality (in comparison with the reference population) for each age group ranged from 10 to 20 percent. The years of potential life lost (YPLL) (life expectancy method) were calculated for the 1988 cohort and compared with the YPLL due to other selected conditions calculated from official vital statistics. The YPLL rates (per 1000 persons) were as follows: hip fracture 9.2, ischemic heart disease 73, cerebrovascular disease 29, breast cancer 20 and cancer of the uterus 6.7. We propose that hip fracture mortality data should be continuously registered and evaluated using the YPLL method to detect changes caused by the expected increase in the number of hip fractures. PMID- 1609594 TI - Epidemiology of pelvic fractures in a Swedish county. AB - Epidemiologic features of pelvic fractures from 1976 to 1985 inclusive were studied in Skaraborg County, southwestern Sweden. The county had an average population of 269,000 inhabitants. During the 10-year period, 541 patients with pelvic fractures were treated in the hospital, and the incidence was 20 per 100,000. The incidence increased in the elderly, especially among women. Severe trauma dominated in age groups below 60 years, whereas moderate trauma dominated in older age groups. 81 percent were stable fractures of the pubic rami and 10 percent acetabular fractures. Associated injuries occurred in 21 percent of the patients, predominantly in those with severe trauma. The mean length of hospitalization was 3 weeks irrespective of whether or not the trauma was moderate or severe. PMID- 1609595 TI - Inhibition of bacterial adhesion by tobramycin-impregnated PMMA bone cement. AB - We investigated the effect of tobramycin-impregnated polymethylmethacrylate (PMMA) bone cement on the adhesion and colonization of Staphylococcus epidermidis. The pattern of colonization was quantitated using plate count techniques and electron microscopy. Colonization of the tobramycin-impregnated disc surface by adhesive bacteria was demonstrated but it was less than in the control disc. This finding suggests that tobramycin may reduce bacterial adherence and proliferation on the PMMA surface. PMID- 1609596 TI - Prognosis in postoperative discitis. A retrospective study of 111 cases. AB - 111 cases of postoperative discitis during 1968-1986 were analyzed retrospectively. The diagnosis was confirmed by lumbar tomography. Low back pain appeared at an average of 16 days postoperatively. Laboratory findings were of minor value in the diagnosis since elevated ESR, white blood cell count, and body temperature were inconstant findings. Compared with a matched control group, there was a higher incidence of chronic low back pain and vocational handicap in the discitis patients. There was no difference in the consumption of analgetics, the subjective evaluation of the final outcome, spinal mobility or neurologic findings. PMID- 1609597 TI - Bone loss after locked intramedullary nailing. Computed tomography of the femur and tibia in 10 cases. AB - 10 patients with previous femoral shaft fracture treated with locked intramedullary nailing were examined by computed tomography (CT) a few days after nail removal. The bone density, cortical thickness and geometric shape of the fractured extremity were compared with those on the contralateral side. Only a small reduction in cortical density and thickness (4 and 7 percent, respectively) was revealed outside the fracture area in the diaphyseal part of the nailed bones. A distinct reduction in trabecular density was observed in the femoral condyles as well as in the ipsilateral tibial condyle (19 and 17 percent, respectively). Our results indicate that the stress-reducing effect of intramedullary nails on the femoral diaphysis is small. PMID- 1609598 TI - The Souter-Strathclyde elbow replacement in rheumatoid arthritis. 13 patients followed for 5 (1-9) years. AB - 13 Souter-Strathclyde unconstrained elbow prostheses for rheumatoid arthritis were followed for 5 (1-9) years. Pain relief was achieved in all the patients. Flexion-extension was increased by 22 degrees, and pronation/supination by 27 degrees. There were no infections. Three humeral components were radiographically loose, but no patient had any symptoms. One patient sustained a fracture of the distal humeral epicondyle, two patients developed neuropathies and one patient had a postoperative dislocation that needed treatment with an external Hoffman fixator. PMID- 1609599 TI - Healing of cortical bone grafts in athymic rats. AB - We studied healing of allogeneic and syngeneic cortical tibial segment grafts in athymic and normal rats. After 3, 6, and 12 weeks, the weight, circulation, and mineralization rate of the healing segment, and mechanical strength and stiffness of the healing tibia were measured. There were no differences between allogeneic and syngeneic grafts in athymic and normal animals at 3 or 6 weeks. After 12 weeks, the vascularization and mineralization of the grafts, but not of the surrounding callus, were smaller in the allogeneic grafts in the normal recipients than in the other groups. Also after 12 weeks, the stiffness of the healing tibiae was less in allogeneic grafts in normal recipients than in the other groups. The strength of the allogeneic grafts was less than the strength of the syngeneic grafts in both athymic and normal recipients. This suggests that T cell-mediated rejection is responsible for decreased vascularization and mineralization of allogeneic bone and that the difference in strength between allogeneic and syngeneic grafts is not due to T-lymphocyte graft rejection. PMID- 1609600 TI - Suture of the torn anterior cruciate ligament. 5-year follow-up of 60 cases using an instrumental stability test. AB - 60 patients were examined 5 (2-9) years after simple suture of acute rupture of the anterior cruciate ligament. In the follow-up the patients were examined clinically and by instrumental testing of stability (Acufex Knee Signature System). 10 knees had had a ligament reconstruction during the follow-up period, 28 knees were stable, and 22 unstable. By the Lysholm knee-score, function was rated excellent or good in both stable and unstable knees and the Tegner activity score dropped insignificantly. A positive correlation was found between the measured laxity and the clinical tests. Instrumental stability testing seems to be a reliable supplementary tool in the diagnosis of anterior cruciate ligament insufficiency. Ligament repair by simple suture was not better than reported results on conservative treatment. PMID- 1609601 TI - Tibiotalar contact and fibular malunion in ankle fractures. A cadaver study. AB - Six cadaveric ankles were dissected, preserving medial and lateral ligaments; an axial load of 455N was applied to the tibia supported by the foot and ankle. The unconstrained tibia was moved through 20 degrees of flexion and extension to simulate walking. The tibiotalar contact area was defined using carbon black suspension, recorded photographically, and measured using computerized area analysis. Osteotomy of the distal fibula was performed and fixed with a specially modified plate; a selection of plates provided fixation with 0 degrees or 30 degrees of external rotation in combination with 0 or 2 mm of shortening. The contact area was measured for each of the plates and after division of the deltoid ligament. There were greater than 30 percent decreases in tibiotalar contact with both fibular shortening and external rotation, doubled with a divided deltoid ligament. Anatomic restoration of both fibular length and rotation is essential for normal ankle mechanics. The deltoid ligament has crucial effects on the stability of the ankle mortise. PMID- 1609602 TI - Fracture healing in rats inhibited by locally administered indomethacin. AB - We studied the inhibitory effect of indomethacin on fracture healing in 135 young, male rats after oral administration compared with local application into the fracture. A closed mid-diaphyseal fracture of the left femur was performed in all the rats. The fractures were not immobilized. In one experiment, half of the animals received indomethacin via a stomach tube (2 mg/kg/day) for 10 days; the controls received only the vehicle. In another experiment, 0.5 mg of indomethacin, contained in a bioerodible polyorthoester gel, was injected into the fracture area in half the rats; in the controls, only the gel was injected. In both experiments, random animals were killed on Days 0, 5, 10, and 20. As assessed by radiographs and manual testing, the same inhibition of fracture healing was found regardless of whether indomethacin was given orally or locally. However, the amount of indomethacin that was applied locally was only one fourth of the total dose given orally; no indomethacin was detected in the serum. PMID- 1609603 TI - Comparison of histomorphometry and 85Sr uptake in induced heterotopic bone in rats. AB - Heterotopic bone formation in the abdominal muscle of 45 male 8-week-old Wistar rats induced by implantation of 5, 10, or 15 mg demineralized bone (DBM) powder was evaluated at 4 weeks by 85Sr uptake of the implants and area histomorphometry of the induced bone. Two indices of 85Sr uptake were calculated: the osteogenic index [(counts/min/mg implant)/(counts/min/mg os ilium)] and an index that we have called the osteoquantum index in which the weight of the implant is disregarded [(counts/min implant)/(counts/min/mg os ilium)]. The osteoquantum index showed a linear relationship to the area of the induced bone with a correlation coefficient (r) of 0.90. Only weak linear relationships were found between the osteogenic index and the area of the bone (r = 0.32) and between the osteogenic index and the osteoquantum index (r = 0.33). The osteoquantum index and the area of the induced bone both increased with increasing mass of implanted DBM, whereas the osteogenic index did not change. PMID- 1609604 TI - Tear of an ossified rotator cuff of the shoulder. A case report. AB - A 57-year-old man with an ossified rotator cuff with acute tears was treated by resecting the ruptured part, as well as the ossicles, and by repairing the massive cuff defect with Teflon felt. Six years after surgery, the pain had been completely relieved, and shoulder motion and muscle strength had been recovered. PMID- 1609605 TI - Acute osteomyelitis complicating a closed radial fracture in a child. A case report. AB - Development of osteomyelitis in a closed fracture is very rare. Although it has been reported that trivial trauma may be associated with the subsequent development of acute osteomyelitis, Waldovel et al. (1970) found no evidence that fractures were involved in the etiology of osteomyelitis. We report a case in which the infection, after a closed fracture involved both metaphyses and the diaphysis of the radius. PMID- 1609606 TI - Late neuropathy in chronic dislocation of the radial head. Report of two cases. AB - Two patients developed ulnar and median neuropathy 15-20 years after anterior dislocation of the radial head had been diagnosed in childhood. Anterior dislocation of the radial head should not be considered innocuous. Open reduction with reconstruction of the annular ligament may be indicated. PMID- 1609607 TI - Posterior reduction of a pathologic spinal fracture. A case of indirect anterior dural decompression. AB - In a patient with paraparesis resulting from a pathologic fracture of Th9, which was due to a breast cancer metastasis, indirect anterior decompression via posterior reduction was performed. The rationale for the operation technique was the similarity between a pathologic fracture of the thoracolumbar spine and a traumatic burst fracture. The method, which uses a transpedicular reduction and fixation device, is substantially less invasive than a formal anterior decompression. PMID- 1609608 TI - Gluteal compartment syndrome. A report of 4 cases. AB - Four cases of gluteal compartment syndrome are presented, 1 traumatic and 3 after an overdose of sedatives. Associated lesions included sciatic nerve palsy in 2 cases and acute renal failure in 1. Three cases with intramuscular pressure exceeding 60 mmHg underwent emergency fasciotomy. Intramuscular pressure monitoring is useful for evaluating the effect of fasciotomy. PMID- 1609609 TI - Hemicondylar tibial osteotomy in Blount's disease. A report of 2 cases. AB - Two neglected cases of Blount's disease with severe sloping of the medial tibial condyle and excessive ligamentous laxity are presented. Elevation of the medial tibial condyle gave good results. PMID- 1609610 TI - Tibia vara in focal fibrocartilaginous dysplasia. A report of 2 cases. PMID- 1609611 TI - Fracture of the lateral talus process. A case report. PMID- 1609612 TI - Polyethylene wear in knee arthroplasty. A review. PMID- 1609613 TI - Neuroblastoma. Pathology and biology. PMID- 1609614 TI - Non-Hodgkin's lymphoma with histological features of neoplastic angioendotheliosis. AB - Three cases of non-Hodgkin's lymphoma, B-cell type, identical histologically to so-called neoplastic angioendotheliosis (NAE), are reported. All showed a rapidly progressive clinical course and were not properly diagnosed before death. The lymphoma cells were distributed in many vessels of systemic organs with a tendency to form aggregates. The primary sites in the three cases were probably the adrenal gland, lymph node, and spleen, respectively. In particular, in one case it was suggested that the lymphoma cells had spread from the adrenal tumor to other organs, showing the histological features of NAE. In the literature, the primary sites of NAE have been scarcely mentioned. However, gross tumors were present in some cases. In such cases, it is possible that the tumors could be the primary sites of NAE. We conclude that some non-Hodgkin's lymphomas can exhibit the features of NAE during their course, particularly in the terminal stages. PMID- 1609616 TI - Atypical carcinoid tumor of the lung with amyloid stroma. AB - Atypical carcinoid tumor of the lung with amyloid stroma seen in a 43-year-old woman is reported. The 47 x 45 x 33 mm tumor, located at the periphery of the S8 segment of the resected left lower lobe, revealed Dylon-positive amyloid deposition in the stroma. The argyrophilic tumor cells with occasional mitoses and focal venous involvement predominantly showed immunoreactivity of cytokeratin, neuron-specific enolase, cystatin C, chromogranin A, calcitonin and neuropeptide Y (NPY). Fewer cells were immunoreactive for calcitonin gene-related peptide (CGRP), the alpha-subunit of human chorionic gonadotropin, gastrin releasing peptide, serotonin, methionine-enkephalin and gastrin. Immunoreactive CGRP or NPY were co-localized in calcitonin-positive cells. The amyloid substance was positively labeled only for CGRP. Immunostaining for amylin, a polypeptide isolated from insular amyloid in type II diabetes mellitus or insulinoma showing a 50% homology with CGRP, was negative. The specificity of immunostaining for calcitonin, CGRP and amylin was confirmed by immunoabsorption tests using synthetic human antigens. Immunoelectron microscopic studies disclosed peptide localization in neurosecretory-type granules and CGRP immunoreactivity in extracellular amyloid fibrils. This is the first report describing CGRP as a component of amyloid of endocrine origin. PMID- 1609615 TI - Immunohistological study of nonfunctional parathyroid carcinoma. Report of a case. AB - The histological and immunohistological features of a non-functional parathyroid carcinoma obtained from a 56-year-old woman are reported. Macroscopically, the tumor consisted of many small hemorrhagic nodules and showed adhesion to the thyroid gland and esophageal wall. Histologically, the tumor cells resembled parathyroid chief cells, and showed an island-like or sheet-like arrangement, the former showing cystic degeneration and containing hemorrhagic fluid in the extracellular space. Tumor cells resembling water-clear cells and oxyphilic cells were also observed. Most of the tumor cells had glycogen in the cytoplasm. Immunohistologically, the tumor cells showed no staining with anti-thyroglobulin, JT-95 or anti-calcitonin antibodies. However, they were stained with antibodies against chromogranin A (Ch A) and the N-terminal portion of human parathyroid hormone (PTH (N)). The positive staining with anti-PTH (N) antibody disappeared when the antibody was absorbed with excess synthesized human PTH (N). Immunostaining for PTH (N) and Ch A was useful for differentiation of nonfunctional parathyroid carcinoma from thyroid carcinoma and thymoma. PMID- 1609617 TI - Vasculitis and pyrexia associated with superficial spreading gastric carcinoma. AB - A case of low-grade fever developing about a month before the discovery of gastric carcinoma is reported. No findings of infection or collagen disease were revealed. The fever continued for about 3 months, but promptly disappeared after surgical removal of the tumor. A superficial spreading mucosal carcinoma with minimal invasion to the submucosa was seen in the antrum, showing the features of poorly differentiated adenocarcinoma. In addition, unique venous inflammation was recognized beneath and around the neoplasm. Arteries and lymph vessels did not exhibit any inflammatory changes. It was presumed that the gastric carcinoma had induced phlebitis, which subsequently brought about the fever. As to the pathogenetic mechanism, it was suggested that a substance produced by the carcinoma cells flowed into nearby veins to induce the phlebitis. PMID- 1609618 TI - Papillary renal cell carcinoma. Report of two cases. AB - Papillary renal cell carcinoma is an uncommon variant of renal cell carcinoma which has unique features including hypovascularity or avascularity, extensive stromal macrophage infiltration and better prognosis than that for nonpapillary renal cell carcinoma. Two cases of papillary renal cell carcinoma presenting hypovascular or avascular angiology are presented. Histologically, the two tumors had a purely papillary structure. Papillae were lined by a layer of epithelial cells which lacked prominent cellular atypia, and there were numerous macrophages in the stroma. In addition, in one patient, extensive calcification of the tumor capsule was present. Furthermore, our experience in the present study with imprint cytology indicates that it offers corroborative information for the intraoperative diagnosis made on the basis of frozen section examination. PMID- 1609619 TI - The opioid peptides of the amphibian skin. PMID- 1609620 TI - Different degradation rates of junctional and extrajunctional acetylcholine receptors of human muscle cultured in monolayer and innervated by fetal rat spinal cord neurons. AB - It is well demonstrated that in intact animals the degradation rate of the junctional acetylcholine receptor (AChR) is significantly slower than that of the extrajunctional receptor. Such data, however, are not available for human AChRs because the required experimentation cannot be performed in humans. We have now studied the degradation rate of the junctional and extrajunctional AChRs, utilizing our tissue culture model, in which well-differentiated neuromuscular junctions (NMJs) form on human muscle cultured in monolayer and innervated long term by fetal rat spinal cord neurons. Half-life of AChRs was studied by a method utilizing the autoradiography of 125I-alpha bungarotoxin and computerized video image analysis. Extrajunctional AChRs degraded with a half-life of 1.3 days whereas junctional AChRs degraded with a half-life of 3.5 days. Our studies demonstrate for the first time that in innervated cultured human muscle: (a) the life span of human junctional AChR, is approximately 3 times longer than that of the extrajunctional AChR and (b) the stability of human AChR is neuronally regulated. This system can now be applied to evaluate the influence of pharmacologic agents on the stability of human junctional AChR, which is of potential importance in the treatment of myasthenia gravis and other diseases of the NMJ. PMID- 1609621 TI - Matrigel enhances myotube development in a serum-free defined medium. AB - Previously reported serum-free defined media for muscle cell culture require supplementation with hormones, purified growth factors or attachment factors. This report describes a culture system that enhances embryonic chick, skeletal muscle cell growth and differentiation in a serum-free defined medium, without added specialized trophic factors. Myoblasts adhered more to and proliferated more rapidly on a reconstituted basement membrane substrate, Matrigel, than on rat-tail collagen. Matrigel contains several basement membrane attachment molecules which apparently obviate the need for added purified attachment factors. Matrigel also appeared to play a trophic role in subsequent development by enabling the serum-free growth of myotubes which suggests that Matrigel mediates the cellular interaction of growth or attachment factors. Collagen, on the other hand, did not support serum-free myotube growth. Supplementation of defined medium with increasing levels of horse serum enhanced total protein in myotubes grown on both substrates; protein was higher in Matrigel cultures for each medium tested. The serum-free defined medium supported complete morphological differentiation of myotubes grown on Matrigel and maintained myotube cultures up to 22 days. Fibroblast proliferation was higher in cultures on collagen in defined medium with high serum levels, but was virtually eliminated in cultures on Matrigel in serum-free defined medium. The culture system described supports the differentiation of embryonic muscle cells in a simple, serum-free defined medium, thus providing an in vitro model of developing myotubes which should be particularly useful for studies of regulation mediated by extracellular factors. PMID- 1609622 TI - Lipid peroxidation in rat cerebral cortex during post-ischemic reperfusion: effect of exogenous antioxidants and Ca(++)-antagonist drugs. AB - Although the role of oxidant-antioxidant metabolism in total ischemia and reperfusion in the central nervous system and cardiac myocardium have been well studied, less is known about the consequences of partial ischemic episodes. Here we show that reperfusion contributes to free radical formation as judged by conjugated diene formation. Also, antioxidants and Ca++ antagonists were able to reduce free radical formation. These results would suggest that free radical generation following ischemia and reperfusion may result from more than one injury process in cerebral cortex. PMID- 1609623 TI - Development of the sensory innervation of muscle spindles in the kitten. AB - This is a report of the changes observed in the pattern of sensory innervation of muscle spindles in hindlimb muscles of kittens during the first four weeks of life. The structural analysis, made on teased, silver-stained preparations, was complemented by a series of recordings of afferent responses of kitten spindles during ramp-and-hold stretches of the muscle. The primary endings of spindles from newborn animals showed a large degree of variability in their branching pattern and branches formed a network across the intrafusal fibres. In older animals there was less variability and lateral branches of stem axons began to encircle the intrafusal fibres. The process of maturation was characterized by a more uniform shape of the endings and more complete, evenly spaced, annulospiral terminals. Recordings of the responses of primary endings of spindles during muscle stretch showed that several features of the adult response were already present in the newborn, although the overall rate of discharge was very much lower. It was concluded that the changes observed in the structure of the sensory endings of kitten spindles did not have clearly identifiable physiological correlates. It appears that an annulospiral shape of the sensory terminals is not a necessary prerequisite for the generation of stretch responses. The predominant factor which appears to determine the responses of spindles to stretch is the maturity of the intrafusal fibres, in particular, the bag2 fibre. PMID- 1609624 TI - Osteoclast adhesion and resorption: the role of podosomes. PMID- 1609625 TI - Performance of dual-energy x-ray absorptiometry in evaluating bone, lean body mass, and fat in pediatric subjects. AB - We studied the performance of the dual-energy x-ray absorptiometry method in evaluating bone mineral, fat, and lean soft tissue mass. This method was accurate in quantifying known small amounts of calcium, lard, and lean tissue mass. It was also accurate in evaluating small animal ashed bones, fat, and muscle mass. The analytic sensitivity of the method was 40 mg for calcium, 180 mg for fat, and 270 mg for lean tissue mass. The method was highly correlated to the single-photon absorptiometry method in measuring bone mineral content at the radius bone in 32 children, r = 0.998. There was a difference between the two methods in older children. Long-term precision for a small bone phantom was 2.0%. Total-body, lumbar, and radial bone scans were performed on 14 newborn infants whose gestational ages ranged from 28 to 41 weeks. Both total-body bone mineral and fat mass increased with gestational age and weight. The infant's total-body calcium was also associated with length and lumbar and radial bone densities. The lumbar bone density was associated with birth weight, gestational age, length, body mass index, body fat, and radial bone density. Male infant's lumbar bone density to total-body calcium ratio was higher than female infant's lumbar bone density ratio. Dual-energy x-ray absorptiometry may be used in pediatrics with high accuracy, sensitivity, and precision. PMID- 1609626 TI - Bone mass measurements in the distal forearm using dual-energy x-ray absorptiometry and gamma-ray computed tomography: a longitudinal, in vivo comparative study. AB - Indices of bone mass were measured in 23 volunteers weekly over 14-16 weeks using dual-energy x-ray absorptiometry (DEXA) and special-purpose computed tomography (gamma-CT). In vitro, the precision for both systems was excellent (coefficient of variation less than 0.5%). Over 4 months, the precision in vivo (average CV for all subjects) for DEXA measures (BMD, g/cm2, and BMC, g/cm) varied between 0.6 and 1.1%; with gamma-CT it varied from 1.1% for TBD (g/cm3) to 2.2% for CBD (g/cm3). Correlation between the indices of bone mass measured using DEXA and gamma-CT at the ultradistal site was moderate, but these indices were not correlated at the distal third site. When BMD and BMC were derived from the CT index IBD, however, the correlation between these gamma-CT indices and the corresponding DEXA indices was high for both ultradistal and proximal radial sites. PMID- 1609627 TI - Longitudinal study of bone metabolism after ethanol withdrawal in alcoholic patients. AB - The pathogenesis of osteopenia in chronic alcoholism remains unclear, and many ethanol-related abnormalities have been advocated to explain bone loss. A direct inhibitory effect of ethanol on osteoblast function was suggested by in vivo and in vitro studies. We measured biochemical markers of bone turnover in 12 alcoholic men before and during a 2 week period of alcohol withdrawal, and we compared the results with those obtained in 15 nonalcoholic men. Our alcoholic patients presented with (1) decreased serum concentrations of bone gla protein (BGP), suggesting decreased bone formation; (2) increased urinary excretion of hydroxyproline, suggesting increased bone resorption; (3) increased renal threshold of phosphate excretion without modification of serum PTH concentration, suggesting a direct effect of ethanol on the renal handling of phosphate. The rapid increase in serum BGP concentrations following ethanol withdrawal suggests that low serum BGP concentrations in alcoholics may result from a direct toxic effect of ethanol on osteoblast function and/or numbers. PMID- 1609628 TI - Isolation and purification of osteocytes. AB - An isolation method for osteocytes is described. After removal of the periostea, bone cells were isolated from calvariae of 18-day-old chicken embryos by alternating treatments with collagenase and EDTA. Osteocytes were purified from the heterogeneous bone cell population with the help of the osteocyte-specific MAb OB 7.3 bound to protein G-conjugated magnetic beads. The purity of the osteocyte population ultimately obtained was more than 95%. Osteocytes were found to adhere rapidly to glass or plastic substrates. They showed numerous processes of various types. These processes could branch and make contact with those of other osteocytes. After 1-2 days of culture, the isolated osteocytes formed a network of apparently interconnected cell processes very similar to the osteocyte network in bone. PMID- 1609629 TI - Effects of phorbol myristate acetate on rat and chick osteoclasts. AB - The role of protein kinase C in the regulation of osteoclast function is not known. We therefore compared the effect of phorbol myristate acetate (PMA), which activates protein kinase C, on the resorptive function, motility, and morphology of osteoclasts from rat and chick. PMA caused a significant reduction in resorption pit number in both species; rat osteoclasts were more sensitive, being significantly inhibited at doses of 10(-9)-10(-6) M compared with 10(-7)-10(-6) M for chick osteoclasts. The inactive analog PMA-alpha was without significant effect, and inhibition was not blocked by 10(-6) M indomethacin. In time course experiments, inhibition at 24 h was similar to or greater than inhibition at 6 h, indicating a persistent or progressive effect on bone resorption. Removal of PMA after 6 h prompted partial recovery of bone-resorptive ability in chick osteoclasts but not rat, at least over a 48 h incubation. In time-lapse video studies of rat osteoclasts, 10(-6) M PMA produced an immediate but transient cessation of motility and retraction of the cell margin into prominent filopodia. Motility resumed within 2.5 h after addition, but the osteoclasts remained partially contracted. Chick osteoclasts behaved similarly but showed no formation of filopodia at the cell periphery and a more rapid recovery of motility than rat osteoclasts; chick osteoclasts also underwent a transient vacuolation following PMA exposure, whereas rat osteoclasts did not. Despite differences in the sensitivity of rat and chick osteoclasts to PMA, these results suggest a fundamental role for protein kinase C in the inhibition of osteoclasts from both species. PMID- 1609630 TI - Contrasting effects of parathyroid hormone and insulin-like growth factor I in an aged ovariectomized rat model of postmenopausal osteoporosis. AB - Agents that exert anabolic effects on bone have generally been tested in young or estrogen-replete animals. It is unclear whether these agents exert similar effects in older ovariectomized (Ovx) animals. In this single study we examined the effects of intermittent (daily) human PTH-(1-34) and continuous infusion of human recombinant IGF-I alone and in combination on bone resorption and formation over a 14 day period in an aged Ovx rat model of postmenopausal osteoporosis (2 year-old rats, Ovx at 1 year). Compared to Ovx controls, PTH treatment increased bone mineral content (BMC) and bone volume and stimulated bone formation but had no effect on bone resorption. In contrast, IGF-I treatment reduced BMC and stimulated resorptive activity as assessed by increases in marrow volume, cortical porosity, osteoclast-positive eroded surfaces, and urinary hydroxyproline excretion. IGF-I had no effect on bone formation, but when combined with PTH, IGF-I blunted the response to PTH on the periosteal and endocortical surfaces. In summary, PTH stimulated bone formation in a manner similar to that observed in younger animals and IGF-I stimulated bone resorption rather than formation and blunted the bone-forming response to PTH. The effects of IGF-I in older Ovx rats may differ from those observed in younger estrogen replete animals. PMID- 1609631 TI - Is caffeine consumption a risk factor for osteoporosis? AB - High caffeine consumption has been proposed as a risk factor for osteoporotic fracture, but the evidence associating high caffeine intake with low bone density is inconsistent. We therefore examined the influence of caffeine consumption on bone mineral at six skeletal sites in an age-stratified random sample of white women residing in Rochester, Minnesota. After age adjustment, there was no association between overall caffeine consumption and bone mineral at five of the six sites. In the femoral shaft, however, there was a statistically significant interaction between age and caffeine consumption so that high caffeine intake was associated with slight reductions in bone mineral among elderly subjects but with modestly increased bone mineral at younger ages. When caffeine intake was categorized by source, no consistent influence of coffee, tea, or other caffeinated beverage consumption could be detected on bone mineral. Caffeine intake was, however, positively associated with cigarette smoking and alcohol consumption. After adjusting for age, caffeine consumption was not correlated with biochemical indices of bone turnover, circulating concentrations of estradiol and estrone, or other dietary and musculoskeletal variables. These data suggest that caffeine intake in the range consumed by a representative sample of white women is not an important risk factor for osteoporosis. Among elderly women, however, in whom calcium balance performance is impaired, high caffeine intake may predispose to cortical bone loss from the proximal femur. PMID- 1609632 TI - Mauricio Rocha e Silva: man and work. PMID- 1609633 TI - From histamine to IR-genes to the idiotypic network. PMID- 1609634 TI - Mauricio Rocha e Silva and the discovery of bradykinin. PMID- 1609635 TI - Mauricio, a friendship at all times. PMID- 1609636 TI - Characterization of two enzymes of broad substrate specificity, that cleave bradykinin. PMID- 1609637 TI - Mechanical and neuro-humoral factors in acute aortic coarctation hypertension. AB - The hemodynamic responses and the role of renal nerves in the physiopathogenesis of acute (45 min) aortic coarctation hypertension were studied in conscious rats. The hemodynamic responses elicited by aortic constriction in intact and bilaterally nephrectomized rats were analyzed by means of miniaturized pulsed Doppler flow probes. Anephric rats presented a smaller increase in mean carotid pressure (MCP) and calculated aortic resistance during aortic coarctation than did intact animals. Reflex bradycardia throughout the experiment did not differ significantly between the two groups. The pressor response following aortic coarctation in untreated renal-denervated rats was similar to that found in intact subjects. Renal-denervated rats previously treated with V1-vascular arginine vasopressin antagonist [d(CH2)5Tyr(Me)AVP] showed the same hypertensive response as control renal-denervated rats. Previous treatment of renal-denervated rats with saralasin (an angiotensin II antagonist) produced a significant reduction in the hypertensive response throughout the experiment when compared to untreated renal-denervated rats. Similarly, rats treated with the vasopressin antagonist plus saralasin showed a blunted hypertensive response following aortic coarctation. The results for rats previously treated with vasopressin antagonist plus saralasin did not differ from those obtained with saralasin alone. Overall, the results of aortic coarctation hypertension obtained in the present study indicate that: 1) Anephric rats showed a blunted hypertensive response due to the lack of neuro-humoral release of vasopressor substances (e.g. angiotensin II and vasopressin) triggered by the kidneys, when only the mechanical factor of constriction was present; 2) The lack of afferent feedback from the kidneys in renal-denervated rats for vasopressin release from the central nervous system allowed angiotensin II to play the major physiopathological role associated with the mechanical factor in the hypertensive response. PMID- 1609639 TI - The liver and the kallikrein-kinin system: a brief review. PMID- 1609638 TI - From bradykinin and snake venom peptides to neuropeptide conversion and inactivation. PMID- 1609640 TI - The origin of kinin in human urine. PMID- 1609641 TI - Peptides potentiating kinin actions: a review. PMID- 1609642 TI - Action of plant proteinase inhibitors on enzymes of the kallikrein kinin system. AB - Serine proteinase inhibitors, in the seeds of several Leguminosae from the Pantanal region (West Brazil), were studied using bovine trypsin, Factor XIIa and human plasma kallikrein. The inhibitors were purified from Enterolobium contortisiliquum (Mr = 23,000), Torresea cearensis (Mr = 13,000), Bauhinia bauhinioides (Mr = 20,000), Bauhinia mollis (Mr = 20,000) and Bauhinia pentandra (Mr = 20,000). E. contortisiliquum inhibitor inactivates all three enzymes, whereas the T. cearensis inhibitor inactivates trypsin and Factor XIIa, but does not affect plasma kallikrein. B. bauhinioides and B. pentrandra inhibitors, on the other hand, inactivate trypsin and plasma kallikrein but only the B. pentandra inhibitor affects Factor XIIa, and B. mollis inhibitor causes trypsin inactivation only. Calculated Ki values were between 10(-7) and 10(-9) M. Chymotrypsin, like trypsin, is also inhibited, but with lower affinity. The trypsin inhibitors, isolated from E. contortisiliquum, B. pentandra, B. bauhinioides and B. mollis seem to be of the Kunitz type; the inhibitor purified from T. cearensis is of the Bowman-Birk type. PMID- 1609643 TI - Human plasma kallikrein. Immunoreactivity and activity on natural and synthetic substrates. AB - Human plasma kallikrein (HuPK) is a serine protease found in mammalian plasma. Following limited proteolysis, the enzyme is activated and forms two chains. The light chain occurs with molecular weight 36,000 or 33,000 and contains the active site. The heavy chain occurs with molecular weight of 45,000 and contains the binding site for high-molecular-weight kininogen. Both chains were prepared from active HuPK, following mild reduction with dithiothreitol and carboxymethylation with iodoacetamide. The light chain was isolated in SBTI-Sepharose and its kinetic properties were determined with synthetic derivatives of arginine-p nitroanilides, to investigate any possible alteration of the active site. These studies showed that substrate modifications affected the hydrolytic activity more than the binding capacity. The ability to cleave high-molecular-weight kininogen, as observed for intact kallikrein, was reduced in beta-kallikrein and absent in the light chain, even when equimolar amounts of both light and heavy chains were tested together. Anti-kallikrein antiserum formed immunoprecipitates not only with kallikrein itself, but also with the separated chains. The immunoreactivity of the light-chain was not identical with that of kallikrein. Immunoselected specific antibodies for both chains, depending on the selectivity, reacted with the heavy chain and kallikrein, or with the light chain and kallikrein. These antibodies were shown to be effective in binding radio-iodinated HuPK in the radioimmunoassay developed for intact kallikrein. PMID- 1609644 TI - Biologically active peptides from Bothrops jararacussu venom. AB - The venom of the Brazilian snake Bothrops jararacussu, was found to contain peptides capable of potentiating the smooth muscle contracting activity of bradykinin (BK). Chromatographic separation on Sephadex G-25 and Sephadex G-10 respectively, yielded an active peptide which at a concentration of 0.6 micrograms/ml doubled the effect of a single dose of BK on the isolated guinea pig ileum. HPLC chromatography showed this material to contain one major and 4 minor components. The active peptide was 2-3 times more active than Captopril in the potentiation of the effects of BK on rat arterial blood pressure and on the isolated guinea pig ileum. It also showed marked capacity to inhibit angiotensin I-converting enzyme. PMID- 1609645 TI - The T-kininogen, T-kinin system of the rat. PMID- 1609646 TI - Kininogen changes in the alloxan-diabetic rat. AB - Ten-day alloxan diabetic rats showed substantial increases in plasma T-kininogen, high molecular and low molecular weight kininogens, as well as significant decreases in urinary levels of kallikrein. Changes in T-kininogen were also observed following turpentine inflammatory treatment. In the diabetic rat, inflammatory responses may contribute to T-kininogen increases. PMID- 1609647 TI - Recent observations on mechanisms of storage and release of mast cell histamine. Applicability to other biogenic amines. PMID- 1609648 TI - Kininogen changes evoked in plasma by feeding, pseudo-alimentary, vagal and carbamylcholine stimulation of the rat. AB - Changes in plasma total (BKg), low (LKg), or high (HKg) molecular weight kininogens are indirect means of studying the participation of kinins in biological processes. To investigate kinin involvement in digestive activity, rats fasted overnight, but given access to water, were allowed to feed for one hour. BKg levels increased by 18% (p less than 0.0001); LKg by 29% (p less than 0.01); HKg remained apparently unchanged. Changes were reversed after 120 min. Decreases in circulatory HKg are probably masked by a compensatory response of the organism aimed at rapidly re-establishing kinin precursor levels in the circulation following their consumption by parasympathetic activity accompanying feeding. This conclusion is based on observations showing that fasted rats submitted to sham-feeding caused by visual/olfactory stimulation by food, present extensive (61%) reduction (p less than 0.001) of HKg, but not of LKg. It is further supported by results demonstrating that electrical stimulation of the distal stump of the cut left abdominal vagus nerve, as well as intravenous administration of carbamylcholine, a parasympathomimetic drug, also produce these changes, all of which were prevented by prior atropinization of the experimental animals. These results open the way for investigations on a possible role of kinins in the control of post-prandial vascular changes. PMID- 1609649 TI - Bradykinin modulation of the hydroosmotic effect of the antidiuretic hormone in water-transporting epithelia. AB - Rocha e Silva's utmost contribution to science was the isolation of bradykinin, a naturally occurring nonapeptide known to have a broad spectrum of actions. Amongst them, considerable evidence suggests that the diuretic effects of endogenous bradykinin are, in part, mediated by inhibition of vasopressin stimulated water transport. This is true for both the mammalian renal cortical collecting tubule and the urinary bladder of the toad (functionally analogous to the tubule). A review of the main contributions that led to that knowledge is presented. PMID- 1609650 TI - The action of iodinated kallikrein on the rat uterus. AB - Iodinated kallikrein appeared inactive on synthetic substrates, was unable to liberate kinins from rat plasma, did not cause contraction of the rat uterus and did not potentiate bradykinin activity. After several doses of iodinated kallikrein were applied to the muscle, the contraction caused by kallikrein was blocked, but the response of the preparation to bradykinin was unaltered. If a double dose of kallikrein was applied, the contraction appeared again, and the response to bradykinin was also potentiated. These results support a kinin mediated oxytocic action of kallikrein, and suggest a new interpretation for the mechanism of kallikrein desensitization in this preparation. PMID- 1609651 TI - Kallikrein-kinin system in the plasma of snakes. AB - Using pharmacological preparations suitable for assay of mammalian kinins, it was shown that Bothrops jararaca (Bj) venom and other kininogenases were unable to release kinins from snake plasma. The kallikrein-kinin system presents species specificity in birds. In order to detect such a specificity in snakes, the effects of Bj venom on snake blood pressure and the effect of incubates of snake plasma with trypsin, on snake blood pressure and snake uterus, were studied. The possibility of activating snake plasma kallikrein with ellagic acid, glass beads or kaolin was also investigated. Whereas plasma of the snakes Waglerophis merremii (Wm) and Crotalus durissus (Cd), were shown to contain factor XII, prekallikrein, kininogen, kininases and to present a low but definite activation rate of the kinin system, the plasmas of Bj, Bothrops mojeni (Bm) and Oxyrophus trigeminus (Ot), yielded only kininogen and kininases. Activation of the system was not even detected by the sensitive substrate Ac-Phe-Arg-Nan (acetyl phenylalanyl-arginyl-4nitro-anilide), indicating that the plasma of these species does not possess either factor XII and/or prekallikrein. Snake plasma may constitute an interesting model for the study of blood clotting, fibrinolytic and complement systems. PMID- 1609653 TI - The scientific thinking of Professor Mauricio Rocha e Silva. PMID- 1609652 TI - Histamine and antihistamines in anaesthesia and surgery: from experimental pharmacology to clinical decision making. AB - The problem of whether antihistamines (histamine H1 + H2-antagonists) should be administered prophylactically before surgical interventions rose after animal experiments with hypnotics, opioids, muscle relaxants and plasma substitutes. It could, however, not be solved by classical biomedical research, but needed a heuristic problem-solving strategy. This strategy was formalized and in this way changed into a scientific structure by the thinking-aloud technique and the building of a decision tree with 9 nodes and various study designs to answer questions at particular decision nodes. The first question, whether the incidence of the reactions was high, was answered by several controlled clinical trials. The second question of life-threatening degrees of severity in single cases, was answered by a drug surveillance study. The third question, of whether severe incidents could always be avoided was answered by medical audit. The same was the case if death had to be considered as the final therapeutic failure. The fifth question was, "are the risks of histamine release comparable to other risks in the perioperative period?" They were--if thromboembolism, infection and stress ulcers were considered. The sixth and seventh questions referred to an experimentally and clinically effective prophylaxis. They were answered by animal and clinical studies with histamine antagonists, mainly with dimetindene and cimetidine. Undesired, adverse reactions to prophylaxis are rare since the drugs are given only once. Prophylaxis was calculated to be fairly cost-effective. Problem-solving strategies are very helpful in transferring facts and conclusions from experimental basic research to clinical decision making. This was convincingly demonstrated in antihistamine prophylaxis in anaesthesia and surgery. PMID- 1609654 TI - Parasympathetically-mediated swelling of mast cell granules during feeding. AB - Mesentery mast cells have been observed to swell and to spontaneously return to their original size following feeding of 12-h fasted rats. This effect may be controlled by parasympathetic efferent nerve impulses, since it is inhibited by atropine. It was reproduced in vitro in isolated rat peritoneal fluid mast cells exposed for 30s to 10(-8)-10(-11) M acetylcholine. When examined under the electron microscope, mast cell average granule diameters had increased by 29% (p less than 0.001) following treatment. Swollen granules did not leave (exocytose) acetylcholine-treated mast cells. They gradually and spontaneously returned to their original size. This recovery only differed from that occurring in the fed rat by its greater speed. PMID- 1609655 TI - Histamine levels in tissues of Trypanosoma cruzi-infected mice. AB - Histamine levels of several organs from mice chronically infected with a myotropic strain of Trypanosoma cruzi were determined by bioassay. An increase in histamine content was observed in stomach, small intestine, colon, heart and skeletal muscle, when compared with noninfected weight and age-matched mice. These results suggest that mast cells, the main storage site of peripheral histamine, can play a role in the inflammatory and/or immunologic components of experimental trypanosomiasis. PMID- 1609656 TI - Insulin, glucocorticoids and the control of inflammatory responses. PMID- 1609657 TI - [Clinical study on primary aldosteronism--localization of adrenal tumors]. AB - Seven cases of primary aldosteronism were experienced during the 12 years in the Toyama Medical and Pharmaceutical University Hospital. The majority of cases were between 32 and 64 years old with a mean of 51 years. Two cases were male and 5 were female. Hypertension was observed in 6 cases, but one case had normal blood pressure. Hypokalemia was recognized in 6 cases. The plasma level of aldosterone was high in all cases and all the cases showed low levels of plasma renin activity. Concerning the localization of the lesions, CT scan, magnetic resonance imaging and adrenal scintigraphy revealed an accuracy rate of 100%, each. Therefore, these imaging techniques are very useful tools for identifying the locality of the adenoma. On the other hand, the accuracy rates of adrenal venous aldosterone assay and ultrasonography were 83 and 60%, respectively. The cases with rather short duration of hypertension before surgery returned to normal in blood pressure earlier after the operation than the other cases. PMID- 1609658 TI - [Postoperative adjuvant M-VAC chemotherapy for invasive bladder cancer]. AB - Between 1986 and 1989, 14 patients undergoing cystectomy for bladder cancer, in pathological stage high risk pT2 group, pT3-4 and/or with N+ disease, received postoperative adjuvant methotrexate, vinblastine, doxorubicin and cisplatin (M VAC) chemotherapy. Of the 14 patients 10 were alive with no evidence of disease for an average of 41 months. Tumor recurrence was seen in 4 patients (bone in 2, lungs in 1, brain in 1 patient). Of the 4 patients, 3 patients died of cancer progression at an average of 26 months and 1 patient was alive with tumor for 30 months. Their actual survival rate at 64 months was 70%, which was significantly higher than that of the historical control groups (1974-1981: 18%, 1982-1985: 46%). Although postoperative adjuvant M-VAC chemotherapy for invasive bladder cancer seemed effective in this study, a controlled randomized study will be necessary to conclude if it could be of real benefit for these patients. PMID- 1609659 TI - [Response of human urinary bladders to angiotensins: comparison between neurogenic and control bladders]. AB - The response of the human detrusor muscle to angiotensins and the difference in contractility between neurogenic and control bladders were examined. Both angiotensin I and II induced potent contraction of the human detrusor muscle. In Ca-free Krebs' solution the contractile response to angiotensin II was abolished. However, verapamil and indomethacin suppressed it only slightly. Captopril blocked completely the response to angiotensin I, and saralasin inhibited completely the response to both angiotensin I and II. The contraction strength in response to both angiotensin I and II was significantly weaker in the neurogenic bladder than in the control. However, there was no difference in the value of ED50 between the two groups. These findings suggest that angiotensin I is converted to angiotensin II by angiotensin converting enzyme at the detrusor, and that angiotensin II subsequently contracts the detrusor muscle through angiotensin II receptors. The contractility of the neurogenic bladder in response to angiotensin was significantly lower compared to that of the control. PMID- 1609660 TI - [Visualization of the intravesical urine stream]. AB - Although many urodynamic techniques have been used to evaluate the function of the lower urinary tract, the principles of these measurements are only based on a relationship between flow rate and pressure. In addition to these measurements, the intravesical urine stream would provide useful information on urodynamics. We have experimentally attempted to visualize the urine stream in a bladder using transrectal ultrasound examination. Since an air-particle is a good target for ultrasound visualization, we instillated a 10% glycerine solution into the bladder for the maintenance of air-particles. Before instillation, this glycerine solution was strongly shaken so that air-particles were kept in the solution. The urine stream was successfully observed throughout the whole process of voiding. In video-recording analysis, the velocity of urine stream was measured by tracing some air-particles. The velocity of urine stream was approximately 28.4 cm/sec in the body and increased to 116.6 cm/sec at the bladder neck. Thus, the urine stream was accelerated toward the urethra during voiding. Therefore, it seems that visualization of the urine stream offers a new parameter for evaluation of urodynamic studies. PMID- 1609661 TI - [Clinical study on 15 cases of torsion of the spermatic cord]. AB - We experienced fifteen cases of torsion of the spermatic cord during the past 10 years. The age distribution was from 10 to 40 years old and the average age was 21.1 years. All cases except one case of right undescended testis occurred on the left side. To our interest, the onset in 12 of the 13 cases with known onset time were during sleep or within one hour after waking up. All cases except one case in the undescended testis complained of pain of the testis and some of them were accompanied with pain in the inguinal and lower abdominal region. Swelling and tenderness of the testis were observed in most cases and shortness of the spermatic cord probably caused by torsion and secondary inflammation seemed to be important findings. Prehn's sign and fever up were observed in few cases but leukocytosis was seen in 10 cases. Eleven cases of surgical treatment consisting of 10 orchiopexy and one orchiectomy were performed. Four cases of spontaneous detorsion were included in our experience. Orchiopexy of the contralateral intact testis was not done, but, we have never experienced relapse of torsion. PMID- 1609662 TI - [Clinical study of parathyroidectomy of secondary hyperparathyroidism in patients with chronic renal failure]. AB - We performed parathyroidectomy for renal osteodystrophy due to secondary hyperparathyroidism on 16 patients with chronic renal failure who were refractory to medical management; subtotal parathyroidectomy on one patient and total parathyroidectomy with autotransplantation on 15 patients. Postoperative clinical improvement, i.e., bone and/or joint pain, pruritus and radiographic signs of renal osteodystrophy, was marked. After the operation, serum calcium decreased rapidly and adequate calcium replacement therapy was necessary. The levels of intact parathyroid hormone decreased rapidly and serum concentration of alkaline phosphatase gradually decreased for a few months postoperatively. Recurrence was diagnosed in one patient, who underwent excision of the transplanted parathyroid tissue. Osteomalasia due to hypoparathyroidism was not seen clinically in this series. In preoperative image diagnosis, ultrasonotomogram (US) showed the highest detective rate of the enlarged parathyroid glands. However, combination of US, computerized tomography and 99mTcO4(-)-201T1C1 scintigram can be recommended as a localizing diagnostic method for compensating the disadvantages of each method. Clinical results after parathyroidectomy for secondary hyperparathyroidism are considered to be good. However, long-term followup is mandatory for early detection of persistent hyperparathyroidism or hypoparathyroidism. PMID- 1609663 TI - Retroperitoneal ganglioneuroma: a case report. AB - A primary extra-adrenal retroperitoneal ganglioneuroma was found incidentally in a 17-year-old boy during a series of examinations for hematopyuria. Computed tomography and magnetic resonance imaging revealed a homogenous mass located between the right proximal ureter and the inferior vena cava just below the right kidney. Subtotal resection of the tumor was performed through a transabdominal approach. The resected specimen measured 8.5 x 6 x 5.5 cm and weighed 70 g. Histological examination showed that the lesion was an extra-adrenal retroperitoneal ganglioneuroma composed of mature ganglion cells and nerve fibers without any malignant features. The patient has shown no signs of recurrence in the 4 months after surgery. We provide a review of the Japanese literature on extra-adrenal retroperitoneal ganglioneuroma and also discuss the clinical features of this tumor. PMID- 1609664 TI - [Multilocular cystic renal cell carcinoma: report of a case]. AB - We report a 76-year-old man with a multilocular cystic renal cell carcinoma resembling a multilocular renal cyst by radiological diagnosis. His creatinine clearance was 43 ml per minute and we carried out simple enucleation, to avoid renal failure after radical nephrectomy and because of low percentage of local recurrence after renal conservative surgery of low stage renal cell carcinoma. We have been following up the patient carefully. PMID- 1609665 TI - [A case of renal cell carcinoma with erythrocytosis]. AB - A case of renal cell carcinoma with erythrocytosis is presented. A 51-year-old man was referred to us for evaluation of left renal mass. Laboratory data revealed marked erythrocytosis and elevated serum erythropoietin level. These data were normalized after removal of the left kidney. Pathological diagnosis was adenocarcinoma of clear cell type. PMID- 1609666 TI - Inverted papilloma of the renal pelvis associated with renal cell carcinoma: a case report. AB - Twenty-one cases of inverted papilloma of the renal pelvis have been described in the literature. A 71-year-old man was admitted to our hospital to examine a right renal mass. We diagnosed a right renal tumor on the basis of the findings from excretory urogram (IVP), computerized tomography (CT) and magnetic resonance imaging (MRI). Surgical material revealed an inverted papilloma in the renal pelvis. We report on the first case of an invested papilloma of the renal pelvis associated with renal cell carcinoma. PMID- 1609667 TI - [Primary carcinoma in situ of the upper urinary tract: a case report]. AB - A case of primary carcinoma in situ of the upper urinary tract in a 72-year-old woman is reported. The patient who complained of left lower abdominal pain was referred for a suspicion of left ureteral stone. An excretory pyelogram showed mild left ureteral stricuture at the level of L3, but a stone was not detected in the ureter at the same level. Cytology of voided urine was positive for malignant cells several times. Cystoscopic examination revealed no abnormality in the bladder. Retrograde left pyelogram demonstrated the ureteral stricture and no lesions either of stone or tumor in the ureter. However malignant cells were detected cytologically in the left ureteral catheteral urine. Left total nephroureterectomy with the bladder cuff was carried out under the preoperative diagnosis of carcinoma in situ of the upper urinary tract. Macroscopically, the wall of the ureter at the stenotic level had induration without apparent tumor mass. The pathological diagnosis was transitional cell carcinoma in situ from the renal pelvis to the mid-ureter. The primary carcinoma in situ of the upper urinary tract is rare. To our knowledge, this case is the 26th case reported in the Japanese literature. PMID- 1609669 TI - 2,8-Dihydroxyadenine urolithiasis due to partial deficit in adenine phosphoribosyltransferase: a case report. AB - Inherited metabolic diseases resulting in urolithiasis secondary to urinary excretion of insoluble substances are rare but often present as urinary obstruction of renal insufficiency. We herein report a case of partial adenine phosphoribosyltransferase deficiency associated with 2,8-dihydroxyadenine urolithiasis. In family members the propositus and his younger brother are homozygotes for defective APRT genes, and who exhibits the type II phenotype designated APRT*J (Japanese type). PMID- 1609668 TI - [Bilateral ureteral obstruction secondary to aneurysm of abdominal aorta: a case report]. AB - A 66-year-old man with the chief complaint of oliguria had been referred to our hospital under the diagnosis of bilateral hydronephrosis and abdominal aortic aneurysm by his family doctor. CT scan and digital subtraction angiography demonstrated an abdominal aortic aneurysm continuing to bilateral internal iliac arteries. The degree of right hydronephrosis was less advanced compared to the left side. Right percutaneous nephrostomy was performed because the retrograde stenting was unsuccessful. After the renal function improved, an operation for the aneurysm was undertaken in the surgical department. Although bilateral ureterolysis was possible, the resection of the aneurysm could not be done. After clamping the nephrostomy catheter, drainage of urine into the ureter was not seen one month after the operation. A double-J ureteral stent was inserted by the antegrade approach and the nephrostomy tube was removed. By exchanging the stent every 3 months, the renal function has been stable and the size of the aneurysm unchanged during the 25 months after the surgery. PMID- 1609670 TI - [Renal pelvic extravasation of urine associated with ureteral stones: report of two cases]. AB - We report a case of spontaneous rupture of the renal pelvis and a case of spontaneous peripelvic extravasation, which were associated with ureteral stones. Case 1 was in a 73-year-old man with complaint of left flank pain. Excretory urograms showed left spontaneous rupture of the renal pelvis associated with left ureteral stone. Double-J ureteral stent was placed immediately and transurethral ureterolithotripsy (TUL) was performed after disappearance of extravasation. Case 2 was in a 34-year-old woman with complaint of left flank pain. Excretory urograms showed left ureteral stone and spontaneous peripelvic extravasation. The stone passed spontaneously and the extravasation disappeared with conservative therapy. PMID- 1609671 TI - [The perineal implantation of a bladder tumor through urethro-vasal reflux]. AB - Perineal implantation of urinary bladder cancer in a 57-year-old male is reported. The patient had been suffering from incomplete paraplegia and neurogenic bladder for these 29 years because of accidental injury of lumbar spinal cord with episodes of bladder stones two times and right epididymitis three times, and presented urinary leakage from a perineal fistula. The fistula orifice was surrounded by a hard mass lesion. Bilateral swelling of inguinal lymph nodes was present. Fistulogram and voiding cysto-urethrography revealed reflux from posterior urethra to the fistula through right vas and epididymis. Histological diagnosis of resected perineal mass and biopsied left inguinal lymph node was transitional cell carcinoma with predominant metaplasia of squamous cell carcinoma. Tissues obtained by TUR-biopsy of a mass lesion at bladder wall was also histologically diagnosed transitional cell carcinoma with metaplasia of squamous cell carcinoma. The present case indicates implantation of a bladder tumor to perineum by urethero-vasal reflux and metastases to inguinal lymphnodes from the perineal lesion. PMID- 1609672 TI - [A giant bladder stone with a small urethral stone]. AB - A 71-year-old man had pollakisuria, macrohematuria and sense of urinary retention. His urethrogram showed a giant bladder stone with a small urethral stone. He received cystolithotomy. The giant bladder stone was removed. It weighed 310 g and is the 32nd reported in Japan. PMID- 1609673 TI - [Cavernous hemangioma of the spermatic cord: a case report]. AB - Cavernous hemangioma of the spermatic cord is a very rare disorder. A 26-year-old man was admitted to our hospital with chief complaints of right intrascrotal mass and hematospermia on October 19, 1990. Physical examination revealed a hard, non transilluminated mass in the right spermatic cord. The mass was resected via the groin. Pathological examination showed cavernous hemangioma. The patient's postoperative course was uneventful. This is only the fourth case of cavernous hemangioma of the spermatic cord to be reported in the literature in Japan. PMID- 1609674 TI - [Vasitis nodosa suspected of the spermatic cord tumor: a case report]. AB - We report a rare case of vasitis nodosa. A 54-year-old man was found to have a right spermatic cord mass during the herniorrhaphy operation. There was no history of surgical or traumatic causes. An indurated mass in the right spermatic cord was suspected to be spermatic cord tumor, and a right high orchiectomy was performed. Histological examination revealed disruption of the ductal lumen, granulomas with the sperm-like necrotic tissue and proliferation of the lymphocytes and plasma cells in the smooth muscle bundles. Pathological diagnosis was vasitis nodosa. PMID- 1609675 TI - [Clinical statistics on the operations during a three-year period (1988-1990)]. PMID- 1609676 TI - [Statistics on operations at Hara Genitourinary Hospital (1971-1991)]. AB - The statistical analysis of the inpatients and operations in our department from April, 1971 to March, 1991 revealed a total of 9,170 operations. One of the biggest changes in treatment is a marked increase in closed surgery. This includes endourological surgeries; transurethral resections of prostate and bladder tumor (TUR-P, TUR-Bt), percutaneous nephrolithotripsy (PNL), transurethral uretero-lithotripsy (TUL) and extracorporeal shock-wave lithotripsy (ESWL). From 1976 to 1980 there were 721 open surgical procedures (71.0% of cases) and 295 closed procedures (21.0% of cases). This ratio has now been reversed completely. From 1986-1991, there were 342 open procedures (8.2% of cases) and 3808 closed procedures (91.8% of cases). The main reason for this change was the introduction of the new techniques PNL, TUL and ESWL. Other important observations include: The incidence of emergency operations was higher in this private institution than that seen in non-private hospitals. From 1986, there was an increase in the use of PNL and TUL for the management of urinary calculi, and from 1988, ESWL has overtaken PNL and TUL in the treatment of this condition. Recently the limitations of ESWL have been appreciated and the value of a combined approach to therapy, for selected cases, is being recognized. A total of 238 ileal or ileocecal conduits were created with good results. A low complication rate has been observed with preservation of renal function. PMID- 1609677 TI - [Acute nongonococcal epididymitis--pharmacological and therapeutic aspects of levofloxacin]. AB - We performed basic and clinical studies on the effects of a new oral quinolone derivative, levofloxacin (LVFX, Code No. DR 3355) which is an optical l-isomer of ofloxacin, in acute epididymitis. LVFX was administered in a dose of 200 mg to prostatic cancer patients 2 hours before operation. The mean concentration of LVFX in the tissues of testis and epididymis were 4.73 micrograms/g and 313-3.6 micrograms/g, respectively. Tissue/Serum ratios were 1.63 and 1.16-1.32, respectively. LVFX was administered in a dose of 100 mg three times daily for 13 days to healthy male volunteers. Semen and blood samples were taken 2 hrs after 7th and last day of administration. The concentration of LVFX in semen were 1.19 micrograms/ml (7th day) and 1.32 micrograms/ml (13th day). Semen/serum ratios were 1.12 and 1.26, respectively. No affection of LVFX on the sperm was observed. Antimicrobial activity of LVFX to C. trachomatis showed good MICs of 0.25-1.0 micrograms/ml. LVFX was administered in a dose of 100 mg two or three times daily for 14 days to 23 patients with acute epididymitis. The overall efficacy rate based on a criteria for acute epididymitis showed 100% (excellent: 16, good: 4, 20/20). A better efficacy rate was obtained on the 14th day than 7th day. No subjective or objective adverse reactions were observed. PMID- 1609678 TI - [Bacteriological and clinical studies on levofloxacin in male gonococcal urethritis]. AB - We performed basic and clinical studies in male gonococcal urethritis on a new oral antimicrobial agent, levofloxacin (LVFX, DR-3355), a new quinolone derivative. The antibacterial activity of LVFX against clinical strains of Neisseria gonorrhoeae was roughly comparable to that of ofloxacin, and ciprofloxacin. LVFX was administered to 10 males with gonococcal urethritis, 200 mg twice a day (8 cases) or 100 mg twice a day for 3 days (2 cases). Clinical evaluation was made according to the criteria of the Japanese UTI Committee. Overall efficacy rate was 100% (10/10). In the complication of chlamydia trachomatis (2 cases), efficacy rate was 100% (2/2). No subjective or objective adverse reactions occurred. PMID- 1609679 TI - Fleischner Lecture. Imaging the respiratory system in the first few years after discovery of the X-ray: contributions of Francis H. Williams, M.D. AB - Imaging of the respiratory system developed with exceptional rapidity in North America during the spring of 1896, after Roentgen's discovery of X-rays in November 1895, largely because of the efforts of a unique physicians, Francis H. Williams. With great zeal, this pioneer used fluoroscopy for early detection of tuberculosis and other life-threatening chest disorders. By the summer of 1896, he had accumulated more than 100 volumes containing tracings of clinical chest fluoroscopy. As a result of his extensive clinical experience, his dedication to patients' welfare, and his sense of scientific inquiry, several inventions and many landmark clinical observations were made in the first few years after the discovery of the X-ray. These included (1) the invention of a "densitometer" for standardized measurements of relative X-ray attenuation of the lung, (2) the invention of a "seehear" device to correlate auscultative findings and fluoroscopic observations, (3) the recognition that fluoroscopy was more accurate than percussion for estimating mediastinal displacement, (4) the discovery that clinically occult tuberculosis and congestive heart failure could be detected with fluoroscopy, (5) the documentation that unilateral chest disease caused decreased ipsilateral ventilatory compliance and increased contralateral ventilation, (6) the identification of the classical imaging characteristics of tuberculosis, pneumonia, pneumothorax, tension pneumothorax, pleural effusion, hydropneumothorax, emphysema, congestive heart failure, and air trapping. In April 1896, Dr. Williams described the "air bronchogram" in a radiograph of a patient with pneumonia. PMID- 1609680 TI - Ewing's sarcoma of the hand. PMID- 1609681 TI - Three-dimensional time-of-flight MR angiography with a surface coil: evaluation in 12 subjects. AB - We compared three-dimensional time-of-flight MR angiograms obtained with head coils and then with surface coils in five patients with intracranial vascular lesions and in seven normal volunteers to determine if imaging of intracranial vascular anatomy could be improved with the use of a surface coil. Visualization of small peripheral vessels was consistently better with a surface coil than with a head coil at identical small fields of view (FOVs). The surface-coil technique allowed small-FOV imaging of peripheral vascular lesions with higher spatial resolution and signal-to-noise ratio similar to that of large-FOV head-coil images. The use of a surface coil introduced the problem of signal falloff; centrally located vessels were visualized as well or better when a standard head coil was used. We conclude that surface-coil MR angiography can serve as a useful adjunct to routine head-coil MR angiography in the evaluation of peripheral vascular abnormalities. PMID- 1609682 TI - MR imaging of symptomatic peripheral vascular malformations. AB - We performed a retrospective study of symptomatic peripheral vascular malformations to determine if MR imaging can be used to distinguish slow-flow venous malformations from high-flow arteriovenous malformations and arteriovenous fistulas. Twenty-seven MR examinations in 25 patients with malformations outside the CNS were reviewed. Sixteen venous malformations, nine arteriovenous malformations, and two arteriovenous fistulas were included. In all cases, the MR findings were correlated with the results of angiography. The distinction between slow-flow venous malformations and high-flow arteriovenous malformations and arteriovenous fistulas was made primarily on T2-weighted MR images, which showed high signal intensity in venous malformations and flow voids in high-flow lesions. In addition to the previously described MR features of venous malformations (serpentine pattern with septations, associated muscle atrophy, and typical T1 and T2 signal intensities), several new MR features were apparent. Venous malformations had a propensity for multifocal involvement (37%), orientation along the long axis of extremities or affected muscles (78%), and adherence to neurovascular distributions (64%). Prominent subcutaneous fat was commonly seen adjacent to the malformation. MR images of arteriovenous malformations and arteriovenous fistulas also commonly showed muscle atrophy and subcutaneous fatty prominence. Our results show that slow-flow venous malformations can be distinguished from high-flow arteriovenous malformations and fistulas on the basis of spin-echo MR signal characteristics. The associated imaging characteristics help in the differential diagnosis in problematic cases. PMID- 1609683 TI - Government and radiology during the next 60 years. PMID- 1609684 TI - Budd-Chiari syndrome: detection with color Doppler sonography. AB - The value of color Doppler sonography in evaluating newly diagnosed Budd-Chiari syndrome in five patients was studied. Hepatic venous findings included absence of vessels (one patient), flow reversal (two patients), narrowing (four patients), and tortuosity (three patients). Detected collaterals included hepatic venous to hepatic venous (four patients), hepatic venous to subcapsular systemic venous (two patients), and portosystemic (three patients). Hepatic venous spectral Doppler waveforms were flat and essentially aphasic in four patients, indicative of distal hepatic venous compression. The inferior vena cava was markedly compressed in two patients and slightly compressed in one. Color Doppler sonography allowed more reliable and confident identification of irregular, compressed, or otherwise abnormal hepatic veins than did conventional sonography. Color Doppler sonography also showed collateral vessels that were undetected with conventional sonography or other imaging techniques. Our results suggest that color Doppler sonography may be a valuable tool in the initial diagnosis and evaluation of suspected Budd-Chiari syndrome. PMID- 1609685 TI - Insertion of Hickman central venous catheters by using angiographic techniques in patients with hematologic disorders. AB - During a 9-month period, 69 Hickman catheters were successfully inserted by using angiographic techniques in 59 patients with hematologic disorders. A pneumothorax, which did not require drainage, developed in one patient. No other significant complications occurred at the time of insertion. Eighteen catheters were removed electively, 15 are still in situ, six were removed for thrombosis, and five were accidentally removed. Infection precipitated removal in six subjects. Ten patients died with the catheter in place. Five catheters were removed in patients with refractory septicemia of unknown origin. One catheter burst during an injection and had to be removed. Three patients were lost to follow-up. There were 3.24 infectious episodes per 1000 days of catheterization, more than twice the rate found in some other series. The results of this study are compatible with the growing body of evidence in favor of the angiographic insertion of Hickman catheters. The apparently high rate of infection is ascribed to factors other than insertion in the angiography suite, including the high proportion of bone marrow transplantation patients. PMID- 1609686 TI - Wallstent misplaced during transjugular placement of an intrahepatic portosystemic shunt: retrieval with a loop snare. PMID- 1609687 TI - Occult glove perforations: frequency during interventional radiologic procedures. AB - Because the intact surgical glove is an important barrier against exposure to blood and other body fluids, occult glove perforations occurring during procedures may have implications for infection control and protection of health care workers. Although the frequency of occult glove perforations during surgery has been studied, no such data have been reported for interventional radiology. This study was designed to determine the frequency of occult glove perforations in interventional radiology. Gloves used during interventional radiologic procedures were collected and tested for occult perforations according to previously accepted methods. The frequency of occult defects in unused gloves was also determined. A form completed for each pair of gloves indicated length of use, awareness of perforations, and information about the procedure. The anatomic distribution of perforations was also studied. Occult perforations were found in 49 (10%) of 492 used gloves. The frequency of defects in unused gloves was 1% (2/160). Gloves worn fewer than 2 hr had a perforation rate of 7% (29/406), and those worn 2 hr or longer had a rate of 23% (20/86; p less than .0001). Perforations were noticed by the wearer in only three (6%) of the 49 perforations. The perforation rate for inner gloves of a double-glove set was 3% (1/34; the corresponding outer glove also was perforated). Although the 10% rate of occult glove perforation during interventional radiologic procedures found in this series is lower than rates described with surgical procedures, it is not insignificant. The significant increase in the rate of perforation when gloves are worn more than 2 hr suggests that gloves should routinely be changed at or before 2 hr of wear, particularly in procedures involving high-risk patients. PMID- 1609688 TI - CNS complications of cocaine abuse: prevalence, pathophysiology, and neuroradiology. AB - The United States is facing an epidemic of cocaine use by adolescents and young adults from all socioeconomic backgrounds. Epidemiologic data suggest that the use of the drug continues to increase on a year-by-year basis. This is a serious public health problem because cocaine is highly addictive and is associated with a variety of serious complications. In the CNS, these include stroke, intracerebral hemorrhage, vascular spasm, and possibly vasculitis. Seizures and sudden death have been reported. Cocaine use during pregnancy may be associated with fetal hypoxia, intracerebral hemorrhage, and possibly congenital malformations in the neonate. Many of these complications have been recognized only in the last 5-10 years. For example, ischemic changes in the brains of chronic cocaine abusers have been reported only recently. Because even further increases in cocaine use are predicted by drug enforcement officials, it is expected that radiologists will encounter its complications more frequently in the future. Therefore, radiologists should become familiar with the radiologic manifestations of the drug's effects. This article describes the drug's pathophysiology and complications and discusses the evolving role of imaging procedures. PMID- 1609689 TI - MR imaging of the spinal cord: current status and future advances. AB - The advent of MR imaging has dramatically altered the evaluation of suspected myelopathy. MR is far less invasive than traditional imaging techniques and often offers a degree of understanding of an abnormality not previously possible. These achievements have closely followed recent technologic advances, such as the development of contrast agents and the introduction of sequences that permit a reduction in both imaging time and artifacts. The current role of MR in the imaging of spinal cord disorders, including intramedullary tumors, infectious and inflammatory myelitis, demyelinating diseases, vascular lesions, trauma, syringomyelia/hydromyelia, and neurodegenerative disorders, is reviewed. While further improvements will undoubtedly occur, the field of spinal MR imaging appears to be entering a maturing phase. PMID- 1609690 TI - Research at the Mallinckrodt Institute of Radiology: a strategic plan for the 1990s. PMID- 1609691 TI - MR imaging in the management of extracranial malignant tumors of the head and neck. AB - Methods of treating malignant tumors of the extracranial portion of the head and neck have become more sophisticated. Cross-sectional imaging is extremely important in the evaluation of patients with a tumor in the head or neck. Although the complexities of head and neck radiology may be overwhelming, a uniform approach that first determines the location and extent of the primary tumor and then examines the nodal chains for metastatic adenopathy takes much of the mystery out of the process. MR imaging allows improved soft-tissue contrast and direct multiplanar acquisition of data, two advantages over CT. This review describes the current role of imaging in the clinical assessment of a patient with a malignant tumor in the head and neck, including the questions that must be answered before surgery and when MR imaging is the preferred technique. PMID- 1609692 TI - Evolution of white matter lesions in neurofibromatosis type 1: MR findings. AB - To characterize further the evolution of white matter lesions in neurofibromatosis type 1, we reviewed 68 MR images in 43 patients (age, 1-31 years), including 25 follow-up studies (mean interval, 27 months). Lesion number, location, morphology, signal characteristics, and contrast enhancement were assessed. Lesion characteristics and changes thereof were correlated with the patients' ages. Thirty-four patients (79%) had white matter lesions. These lesions were hyperintense on T2-weighted images, were isointense on T1-weighted images, and showed no mass effect or contrast enhancement in 31 patients; in three patients, T1-prolongation was observed (one with significant mass effect). None of the lesions evolved into a glioma. The most common locations were the cerebellum (49%), brainstem (22%), and internal capsule (19%). Nineteen patients had white matter lesions and follow-up studies. Lesions decreased in size or number in seven patients (average age, 13 years), showed no change in three (average age, 12 years), increased in size or number in four (average age, 5 years), and showed a mixed pattern (increased/decreased size/number) in four (average age, 7 years). White matter lesions in neurofibromatosis type 1 frequently increase in size or number early in childhood; this did not indicate neoplasia in our study. The lesions tend to resolve with increasing age. Lesion progression in a child more than 10 years old warrants close follow-up to rule out a neoplasm. PMID- 1609693 TI - Cerebellar and cerebral abnormalities in Rett syndrome: a quantitative MR analysis. AB - Rett syndrome is a neurodegenerative disease of young girls that begins in early childhood with autismlike behavior and loss of language skills, and progresses with marked deterioration of the motor system in the second decade of life. The purpose of this study was to determine if neuroanatomic changes detected with MR imaging could help to explain the clinical presentation and progression of signs and symptoms in these patients. Accordingly, computer-assisted planimetry was used to measure various dimensions of cerebral, cerebellar, and brainstem structures on sagittal and transverse MR images of 13 patients with Rett syndrome and 10 healthy volunteers. Dimensions of the cerebrum, basal ganglia, cerebellum, and brainstem were measured on transverse images. Areas of cerebellar vermian lobules, the fourth ventricle, the pituitary gland, and the corpus callosum were measured on sagittal images. Fourteen dimensions and areas were measured in each patient and each control subject; according to two-tailed Student's t tests, all but two values were significantly smaller in the patients with Rett syndrome than in control subjects. Graphing the measurements against age by using simple linear regression revealed progressive cerebellar atrophy without evidence of atrophy of the brainstem or cerebrum. Our results indicate that patients with Rett syndrome have global hypoplasia of the brain and progressive cerebellar atrophy increasing with age. Cerebellar atrophy with age may contribute to the deterioration of the motor system seen in older patients with Rett syndrome. PMID- 1609694 TI - Radiology ethics. PMID- 1609695 TI - High-signal foci on MR images of the brain: observer variability in their quantification. AB - Foci of high signal in the cerebral white matter are common incidental findings on MR images of the brain of control subjects or patients with a variety of diseases. Although the number of foci has been reported to correlate with age and several risk factors, the degree of observer variability in quantifying foci has not been reported. We used kappa statistics to determine radiologists' agreement in counting high-signal-intensity foci on MR images obtained in healthy volunteers and in patients with hypertension. Before interpreting the images, one pair of radiologists studied 30 routine MR images and reached consensus on differentiating high-signal foci from other foci of high intensity caused by normal structures (e.g., deep gyri or Virchow-Robin spaces). These two observers than independently determined the number of foci in the study group. Using their own criteria, other radiologists independently counted the foci. Agreement between observers was determined with the kappa statistic. The results showed fair agreement between the radiologists who first reached a consensus in counting foci of hyperintensity and poor agreement between the other observers. We conclude that in order to compare the frequency of foci of hyperintensity in different groups of patients, observer variability must be controlled. Studies without proper control subjects may lead to incorrect conclusions regarding the correlation of focal hyperintensities and various risk factors. PMID- 1609696 TI - Iatrogenic air in the cavernous sinus. PMID- 1609697 TI - Current role of cerebral angiography in the diagnosis of cerebrovascular diseases. AB - The role of cerebral angiography in the diagnosis of cerebrovascular disease is currently being questioned because of the increasing availability of MR angiography. The purpose of this essay is to place the use of cerebral angiography in perspective in light of these new developments. In patients with atherosclerotic cerebrovascular disease, MR angiography can almost entirely supplant cerebral angiography as a screening procedure in the evaluation of the carotid bifurcation. However, detection of "pseudoocclusion" still requires cerebral angiography for accurate diagnosis. Atherosclerotic stenosis or occlusion of the major intracranial vessels at the base of the brain can be detected with MR angiography, but not as accurately as with cerebral angiography. Furthermore, for detection of more distal occlusions, cerebral angiography is still needed. A number of erroneous concepts about the risks and value of cerebral angiography have prevented its optimal use for patients with cerebrovascular disease. These myths can be countered by applying several rules to optimize the use of cerebral angiography. Subarachnoid hemorrhage is best evaluated with CT followed by detailed cerebral angiography, although MR angiography can be used as a screening test for aneurysms 3 mm or larger. Cerebral angiography is still necessary to confirm the diagnosis of cerebrovascular malformations, although MR angiography is a useful screening test. Cerebral angiography is required for the definitive diagnosis of arteritis, arterial dissection, or fibromuscular dysplasia. PMID- 1609698 TI - A PACS-based interactive teaching module for radiologic sciences. AB - This article describes an interactive teaching module, linked to a picture archiving and communications system (PACS) data base, for teaching radiology. The module is currently tailored to MR images but can be adapted to any other imaging technique. An algorithm has been developed that allows the use of MR images acquired with routine clinical protocols and stored in the data base to yield, in real time, images at any other arbitrary TE and TR. In the browse mode, the user can study either the effect of different scan parameters or clinical cases on synthesized or acquired images. The quiz mode has multiple-choice questions and answers, accompanied by images. In the teaching mode, the instructor has access to the clinical data base and WRITE privileges for setting up the browse or quiz mode. The module achieves considerable flexibility when linked to the PACS, with access to all archived images and the ability to subsequently synthesize MR images at arbitrary TE and TR values in real time. The module is also "dynamic" in character, in that the instructor can easily add new cases and comments to the teaching files, both to enhance its clinical aspects and to reflect advances in technology. PMID- 1609699 TI - The Society of Gastrointestinal Radiologists: 21st annual meeting, February 1992. PMID- 1609700 TI - The hidden curriculum. PMID- 1609701 TI - Triple vision: a modification of bifocal lenses for radiologists. PMID- 1609702 TI - Pulmonary embolization of iodine-125 implants. PMID- 1609703 TI - Mediastinal lymphangioma. PMID- 1609704 TI - American College of Radiology Mammography Accreditation Program. PMID- 1609705 TI - Dirofilariasis of the breast mimicking carcinoma on mammography. PMID- 1609706 TI - Color Doppler sonography in afferent loop syndrome. PMID- 1609707 TI - Subpectoral mass mimicking a malignant breast mass on mammography. PMID- 1609708 TI - Diagnosis of epigastric appendicitis based on sonographic findings. PMID- 1609709 TI - Small-bowel perforation after preoperative high-dose-rate intraluminal brachytherapy for rectal carcinoma. PMID- 1609710 TI - Detection of hepatic masses in patients with carcinoma. PMID- 1609711 TI - Extrastiff plastic-coated guidewire for percutaneous biliary procedures. PMID- 1609712 TI - Radiologic abnormalities at the harvest site in patients undergoing bone marrow transplantation. PMID- 1609713 TI - Radiation-induced fracture of the sacrum: findings on MR. PMID- 1609714 TI - Duplex sonography of the cerebral arteries. PMID- 1609715 TI - Radiologic evaluation of a Renaissance painting. PMID- 1609716 TI - Value of sonography in determining the nature of pleural effusion: analysis of 320 cases. AB - To assess the value of sonography in determining the nature of pleural effusions, we prospectively analyzed the sonographic findings in 320 patients with pleural effusion of various causes (224 with exudates and 96 with transudates). The nature of the effusions was established on the basis of chemical, bacteriologic, and cytologic examination of pleural fluid; pleural biopsy; and clinical follow up. All patients had high-frequency, real-time sonography performed by one of three sonographers who had no clinical information concerning the patients. The sonographer evaluated the images for internal echogenicity of the effusion, thickness of the pleura, and associated parenchymal lesions of the lung. The images were also printed out and interpreted a second time by the other two sonographers to reach a consensus. Our results showed that the two types of effusions could be distinguished on the basis of sonographic findings. Transudates were anechoic, whereas an anechoic effusion could be either a transudate or an exudate. Pleural effusions with complex septated, complex nonseptated, or homogeneously echogenic patterns were always exudates (p less than .01). Sonographic findings of thickened pleura and associated parenchymal lesions in the lung also were indicative of an exudate (p less than .01). Homogenous echogenic effusions were due to hemorrhagic effusion or empyema. Sonographic evidence of a pleural nodule was a specific finding in patients with a malignant effusion. We conclude that sonography is useful in determining the nature of pleural effusion. PMID- 1609717 TI - Lung torsion after percutaneous needle biopsy of lung. PMID- 1609718 TI - Pleuropulmonary paragonimiasis: radiologic findings in 71 patients. AB - Pleuropulmonary paragonimiasis is a disease caused by lung flukes characterized by migration of a juvenile worm in the early stage and by formation of cysts around the worm later on. The purpose of this study was to describe the radiologic manifestations of pleuropulmonary paragonimiasis, with special emphasis on the worm cyst and worm migration track. We retrospectively studied 71 patients who had evidence of pleuropulmonary paragonimiasis on chest radiographs (n = 71) and CT scans (n = 17). The diagnosis was based on the detection of eggs or on positive antibody tests. On chest radiographs, 59 patients (83%) had pulmonary lesions and 43 patients (61%) had pleural lesions. Pulmonary findings included patchy air-space consolidation (n = 37) with or without cystic changes; ring shadows (n = 16); and peripheral linear opacities (n = 29), which were more prominent in patients with pleural effusion. Twelve patients (17%) had bilateral pleural effusions or pneumothoraces. On CT scans, round low-attenuation cystic lesions (5-15 mm), filled either with fluid (n = 5) or gas (n = 5), were characteristically seen within the consolidation. Peripheral linear opacities seen on radiographs were suggestive of worm migration tracks on CT scans. CT may reveal an intracystic worm. Although the findings vary depending on the stage of the disease, findings on chest radiographs are usually typical of paragonimiasis. CT provides more specific information about the worm cyst and the worm migration track. PMID- 1609719 TI - CT evaluation of poststernotomy complications. PMID- 1609720 TI - Mammographic appearance of loiasis. PMID- 1609721 TI - Gastric leiomyosarcoma. PMID- 1609722 TI - Hereditary hemorrhagic telangiectasia: findings in the liver with color Doppler sonography. PMID- 1609723 TI - Langerhans cell histiocytosis of the liver: imaging findings. PMID- 1609724 TI - Mucocele of the appendix: imaging findings. AB - Mucocele of the appendix, a cystic mass resulting from a dilated appendiceal lumen caused by abnormal accumulation of mucus, is a rare entity that often is not considered when problems of the right lower quadrant are assessed. Preoperative recognition of mucocele of the appendix is important because of the possibility of rupture at surgery with development of pseudomyxoma peritonei and to predict malignant transformation. The appearances of mucoceles of the appendix on sonography, CT, and barium studies are illustrated. PMID- 1609725 TI - Bowel ischemia and perforation after cocaine use. PMID- 1609726 TI - Calcified renal stones and cyst calcifications in autosomal dominant polycystic kidney disease: clinical and CT study in 84 patients. AB - Although renal calculi and cyst calcifications occur commonly in patients with autosomal dominant polycystic kidney disease (ADPKD), their true frequency is unknown because it is difficult to distinguish between the two with excretory urography and sonography. A detailed analysis of renal calcifications in ADPKD based on CT findings has not been performed. Accordingly, we retrospectively evaluated clinical and CT findings in 84 patients with ADPKD to determine the frequency of calculi and cyst calcifications, the relationship of these abnormalities to symptoms, and possible factors in their pathogenesis. Of the 84 patients, 53 had both IV contrast-enhanced and unenhanced CT scans and 31 had unenhanced scans only. We examined unenhanced CT scans of all 84 patients for renal calcifications. However, we classified renal calcifications into stones and cyst calcifications in only the 53 patients, because it is often difficult to distinguish between the two when only unenhanced scans are available. Of 84 patients, 18 (21%) had passed renal calculi or had stones treated surgically and 42 (50%) had renal calcifications on CT. Of the 53 patients who had both enhanced and unenhanced CT scans, 19 (36%) had renal calculi on CT. Patients with stones had significantly higher frequencies of previous flank pain (68% vs 35%) and of urinary tract infections (63% vs 18%) than did those without calculi. Cyst calcifications occurred in 13 (25%) of 53 patients and were probably a consequence of cyst hemorrhage. Cyst calcifications were found significantly more often in older patients with larger kidneys and worse renal function. We conclude that renal stones have a high rate of occurrence among patients with ADPKD and are a significant cause of morbidity in this disorder. Cyst calcification is also common in patients with ADPKD, particularly those with more advanced cystic disease. PMID- 1609727 TI - Diagnosis of placenta previa during the third trimester: role of transperineal sonography. AB - Placenta previa can be difficult to diagnose with transabdominal sonography during the third trimester of pregnancy, because of difficulties in imaging the cervix late in pregnancy. Although transperineal sonography offers an additional view of the cervix, its value in the diagnosis of placenta previa has not been studied. Accordingly, we performed transperineal sonography on 164 patients who had had transabdominal scans that had shown placenta previa or had been inconclusive during the third trimester of pregnancy. Transabdominal sonograms had been inconclusive for placenta previa in 157 of these patients because the cervix was not visualized. The remaining seven patients had transabdominal scans that showed placenta previa. Transperineal sonography successfully visualized the internal surface of the cervix in all 164 patients, allowing determination of the presence or absence of placenta previa in all cases. Transperineal sonograms showed absence of placenta previa in 154 patients. At delivery, none of these patients had evidence of placenta previa. Transperineal sonography showed placenta previa in 10 patients. In nine of these patients, placenta previa was confirmed at delivery. The 10th patient did not have clinically significant placenta previa at delivery. Our study shows that transperineal sonography is a valuable technique to complement transabdominal sonography for detection of placenta previa during the third trimester of pregnancy. Use of transperineal sonography should be strongly considered when a definitive diagnosis regarding placenta previa is not possible by transabdominal sonography because the cervix is not visualized. In such cases, transperineal sonography will usually show the internal surface of the cervix without overlying placental tissue, allowing confident exclusion of placenta previa. Occasionally, however, transperineal sonography will show a placenta previa that was not seen with transabdominal sonography. PMID- 1609728 TI - Ovarian cysts are common in premenarchal girls: a sonographic study of 101 children 2-12 years old. AB - Previous studies of sonograms in premenarchal girls have reported the typical ovary to be homogeneous in echogenicity, with cysts an uncommon finding, particularly in children less than 6 years old. These studies found no macrocysts (cysts greater than 9 mm in greatest length) in patients less than 11 years old. This information contradicts published pathology studies and our sonographic experience. The goal of this study was to determine the prevalence of cysts in the ovaries of premenarchal girls. The pelvic sonograms of 101 consecutive premenarchal girls between 2 and 12 years old, without known gynecologic or endocrinologic disease, were prospectively studied. One hundred fifty-five ovaries were adequately imaged in three dimensions. Ovaries were evaluated for the presence or absence of cysts (as defined by sonographic criteria), and the length of the cyst or of the largest cyst, if several were noted, was measured. Cysts were identified in 106 ovaries (68%). Cysts were seen in patients of all ages, particularly in the younger children (2-6 years old). Thirteen of the cysts, noted in 11 patients between 2 and 10 years old, were macrocysts. The typical sonographic appearance of the ovary in premenarchal girls is not homogeneous. Cysts are common in premenarchal girls between 2 and 12 years old and are the cause of the typical heterogeneous image. Macrocysts can be seen in healthy girls less than 11 years old. PMID- 1609729 TI - The Edward Mallinckrodt Institute of Radiology 60th anniversary rededication program. PMID- 1609730 TI - Prolapsing inverted papilloma of the prostatic urethra: diagnosis by transrectal sonography. PMID- 1609731 TI - Diseases of the lumbar spine: findings on fat-suppression MR imaging. AB - Fat-suppression MR techniques have been useful in imaging both the head and neck and the orbit. The lumbar spine is not as complex as the head and neck and does not contain as much fat as the orbit. Nevertheless, high signal from epidural and marrow fat in the lumbar spine can make it difficult to detect and define pathologic processes. In addition, the administration of gadopentetate dimeglumine can cause some infectious and neoplastic lesions of the spine to become isointense with fat on T1-weighted images. Compared with conventional MR imaging without fat suppression, contrast-enhanced fat-suppression MR imaging can better differentiate these enhancing lesions from surrounding fat. In this essay, we illustrate the findings of fat-suppression MR imaging in a variety of diseases of the lumbar spine. PMID- 1609732 TI - Programs for the deaf. PMID- 1609733 TI - Parent-infant education in schools for deaf children. Before and after PL 99-457. AB - This report looks at parent-infant programming in schools for deaf children nationwide, comparing data from two surveys of these schools, one before and one after enactment of PL 99-457, one in 1982 and one in 1990. Surveys were returned by 107 schools in 1990 (60 residential and 47 day), 81 of which responded both in 1982 and 1990. Of the schools that responded to both surveys, parent-infant programming for children 0-4 years old and their families was reported by 89% in 1982 and 95% in 1990. Enrollment doubled during the period, from 1,602 students to 3,411. The major increases were in the number of students receiving part-time instruction (1/2 to 2 hours per week), which almost tripled, and the number receiving instruction primarily in the child's home. Data are presented on the extent of parent-infant programming and on student characteristics, program funding, and respondent concerns. Implications of these findings and the implementation of PL 99-457 are also discussed. PMID- 1609734 TI - A profile of family education/early intervention services at the Maryland School for the Deaf. AB - Based on demographic data from more than 400 families, this report describes the growth and development of early intervention services at the Maryland School for the Deaf from 1969 to 1992. The implications of this information are discussed as they relate to the very early identification of hard-of-hearing and deaf youngsters, to the impact of changing etiologies, and to the training of early intervention specialists who can meet the needs of these children and their families. PMID- 1609735 TI - Hearing parents and deaf children. Some perspectives on sign communication and service delivery. AB - The results of a survey of hearing parents' perceptions of their use of sign communication with their deaf children are reported. Survey questions addressed parental understanding and motivation in choosing a particular system of sign communication, input from professionals and deaf adults that was found to be most and least helpful, and parental assessment of their service needs. The results of the survey highlight the need for family focused services throughout the deaf child's development, and the discussion includes specific comments made by parents. PMID- 1609736 TI - The role of parents in developing visual turn-taking in their young deaf children. AB - Young deaf children use their vision to gather both language input and information about the environment. This dual requirement greatly complicates conversational turn-taking for the children and their parents, particularly when interaction centers on a visual focus such as a book. Data are presented here on the onset and maintenance of visual attention to signing in three profoundly deaf children, ages 2;9-3;7 years, while interacting with their hearing mothers about a story told through pictures. The data indicate that the children's visual attention in this situation was quite variable, although all of them experienced problems with their need to focus simultaneously on two sources of information: the mother's signs and the picture book. Suggestions for developing visual turn taking skills are made, based on the research on first-language acquisition and the interactions of deaf mothers with their children. PMID- 1609737 TI - Effects of selected process parameters on emission rates of volatile organic chemicals from carpet. AB - There has been increased interest over the last several years in issues related to indoor air quality. Although the factors affecting indoor air quality are recognized to be very broad, ranging from building design, operation, and ventilation to biological contamination, recent emphasis has been placed on chemical contaminants, particularly volatile organic chemicals (VOCs). New floor covering systems, including new carpets, have been identified as a potential, short-term source of VOCs in the indoor air of new or renovated buildings. This report describes an exploratory study designed to examine several manufacturing variables and their effects on VOC emission rates from new carpets. It was based on a statistical experimental design and was conducted at a single carpet mill on a full-scale production line. The outcome variable, VOC emission rate, was examined relative to selected independent variables: latex type, latex amount, makeup air into the drying oven, residence time in the drying oven, and their interactions. Significant variables were identified for a number of emission rate models. The study results suggest that there are no simple answers for easily reducing VOC emission rates, but several conclusions could be inferred from the study as to future directions to pursue. PMID- 1609738 TI - Floor/shoe slip resistance measurement. AB - A variety of slip measurement devices exist that provide estimates of both static and dynamic coefficient-of-friction (COF) values between one's shoes and the floor. Unfortunately, different shoe sole/heel materials, floor conditions, and contaminants will affect the tests in ways that result in widely varying COF estimates. This paper reviews the basic physics of such tests and describes a set of experiments to determine the static and dynamic COF values under operating conditions known to exist in different jobs. The results define a set of conditions wherein low (hazardous) COF values would exist (e.g., hard Neolite shoe material in contact with a wet, smooth walking surface). The results also question the use of light-load testing devices and static and slow speed reference COF values in the literature. PMID- 1609739 TI - Chemical composition and morphology of welding fume particles and grinding dusts. AB - Elemental composition and morphology of pure manual metal arc (MMA) welding fumes, pure grinding dust, and combined fume/dust air samples were collected and determined separately under semilaboratory conditions. The base material was stainless steel. The purpose of the present study was to create a "synthetic" work situation under semilaboratory conditions by combining one grinding period and two MMA welding periods and comparing these results with results during welding in a workshop. The duty cycles of pure welding and of pure grinding were also observed. A comparison was also made between metal inert gas (MIG) and MMA welding on stainless steel as well as a nickel-rich alloy under regular conditions. The amount of collected material was determined by weighing the membrane filters before and after exposure, and the element contents were determined by atomic spectroscopy. Other transmission electron microscopy (TEM) filters were used for TEM and computer-image analysis, in which the amount of collected material and its morphological characteristics were observed. The arcing time and the consumption of filler material were estimated for different kinds of electrodes. Chemical analysis showed that the contents of manganese and total chromium were lower in grinding dust than in welding fumes. The contents of hexavalent chromium, Cr(VI), in grinding dust were undetectable. Samples collected in welding shops where concomitant grinding was performed contained about 30% less Cr(VI) than those collected under laboratory conditions during welding only. The sizes and shapes of the particles depend on the welding process and distance of collection from the plume of the fume. To compare laboratory experiments with regular welding situations, the experiment must resemble industrial welding.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609740 TI - The development of cleanup criteria for an acutely toxic pesticide at a contaminated industrial facility. AB - Sodium fluoroacetate, a restricted-use rodenticide, was improperly applied to kill rats in a South American steel mill. As a result of this application, several workers were seriously injured. During plant decontamination, cleanup levels were developed to ensure that any residual material remaining at the plant did not pose a health risk. Cleanup levels were developed to prevent significant exposure of workers, who could inhale contaminated dust, contact dust, or soil dust in outdoor areas or on plant floors and who could contact contaminated surfaces. On the basis of a health risk analysis, the following cleanup levels for sodium fluoroacetate were developed--air cleanup levels, 0.05 mg/m3; soil/dust cleanup levels, 100 mg/kg; and wipe sample cleanup levels, 0.2 mg/100 cm2. These risk-based cleanup levels were ultimately used to assist the regulatory agencies in reaching a decision to reopen the plant. PMID- 1609741 TI - Breakthrough time and adsorption capacity of respirator cartridges. AB - A model developed in previous studies was applied to investigate the respirator cartridge contaminant breakthrough of 121 different chemical compounds. Included in this set of 121 contaminants are representative examples of various types of organic compounds, (e.g., acetates, ketones, aromatics, alcohols, amines, alkanes, chlorinated hydrocarbons). Intrinsic to the model are two important parameters, k' (a rate constant) and tau (50% breakthrough time). Values of the two parameters pertinent to an assault concentration of 1000 ppm were determined for each of the 121 organic compounds. These values were used to calculate the breakthrough time at specified fractional breakthrough as well as the respirator cartridge loading capacity under various conditions. An approach was presented that permits the determination of contaminant loading capacity (on carbon) as a function of breakthrough time at a specified assault concentration. The effect of contaminant assault concentration on the saturation capacity was investigated for various combinations of nine different compounds and three different types of respirator cartridges. Calculated saturation capacity data derived from application of the model compare favorably (+/- 5%) with corresponding experimental data. Saturation capacities calculated by using the model addressed in this study were compared with corresponding results previously calculated by others using the Dubinin adsorption isotherm. PMID- 1609742 TI - Polycyclic aromatic hydrocarbons (PAHs): a possible cause of lung cancer mortality among nickel/copper smelter and refinery workers. AB - A retrospective industrial hygiene investigation was undertaken to explain the cause of a statistically significant excess lung cancer mortality observed in a subset of a large cohort of nickel workers involved in mining, smelting, and refining of nickel and copper in Ontario. The focus of this paper is to demonstrate how an industrial hygiene follow-up assessment of an epidemiologic finding can help to identify a likely cause. Polycyclic aromatic hydrocarbons (PAHs) alone or in association with particulate and gaseous contaminants (e.g., SO2) were likely the causative agents of the excess lung cancer observed among the lead welders, cranemen, and arc furnace workers of the copper refinery. PMID- 1609743 TI - Experimental examination of factors that affect dust generation by using Heubach and MRI testers. AB - Four factors that affect dust generation were investigated--type of test material, particle size distribution of the test material, moisture content of the test material, and apparatus used to generate dust. Dust generated from silicon carbide and aluminum oxide was measured by using MRI and Heubach dustiness testers modified to allow the measurement of dust particle size distribution with an Andersen impactor. The two materials investigated generated similar dusts. The size distribution of the test material slightly influenced the amount but strongly influenced the size distribution of the dust generated. Increased moisture content decreased the amount of dust generated; moisture content had little influence on dust size distribution. The two testers generated different amounts of dust; however, the dust particle size distributions generated were similar. These results help explain factors that affect dust generation and the relative importance of alternative methods for dust control. PMID- 1609744 TI - Occupational exposure to 1,6-hexamethylene diisocyanate-based polyisocyanates in the state of Oregon, 1980-1990. AB - Monitoring of exposure to 1,6-hexamethylene (HDI) monomers and HDI polyisocyanates in Oregon was initiated in 1980 and covered primarily spray painting and related activities. A total of 562 air samples were collected from 60 workplaces during the years 1980-1990 and analyzed for HDI and HDI polyisocyanate content. Of the total, only a small fraction (6%) of the samples exceeded the state of Oregon permissible exposure limit (PEL) of 0.02 ppm for HDI monomer; however, a much higher number (42%) of the samples exceeded the Oregon PEL of 1 mg/m3 for HDI polyisocyanates. Spray finishing operations were divided into three categories: continuous industrial spraying, auto body repair shops, and intermittent spray operations of large objects. The highest exposures among all three categories for both HDI and HDI polyisocyanates were measured during spray finishing. The geometric mean for HDI in the industrial spray operations was 0.001 ppm and for HDI polyisocyanates was 3.78 mg/m3. Frequently, the peak exposures exceeded the Oregon PEL for polyisocyanates, reaching as high as 12.2 mg/m3. In auto body shops, the mean for HDI was 0.002 ppm and for HDI polyisocyanates was 1.60 mg/m3 with peak concentrations of 0.049 ppm for HDI and 18.4 mg/m3 for HDI polyisocyanates. In the third category of spray finishing of large objects, the geometric means for three subcategories ranged from 0.001 to 0.017 ppm for HDI with a peak concentration of 0.069 ppm. The geometric means for HDI polyisocyanates ranged from 2.09 to 15.9 mg/m3 with a peak of 29.5 mg/m3. In all the surveys, the ventilation facilities and personal protective equipment were evaluated.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609745 TI - Release of bacterial aerosols during infectious waste compaction: an initial hazard evaluation for healthcare workers. AB - Compaction has been suggested as an interim processing method for infectious waste. Compaction greatly reduces the volume of waste at the site of generation and produces a more stable package for handling, shipment, and treatment. Preliminary studies have also indicated that when partially compacted waste is burned in an incinerator, the performance of the incineration unit is enhanced. Compaction is not currently used in institutions because the process may lead to the release of infectious aerosols, which could pose a significant hazard to healthcare workers. To determine if bacterial releases can be adequately controlled by a compaction device specially designed and constructed for the task, a prototype infectious waste compactor was challenged by compressing waste containing known quantities of indicator bacteria. Samples were collected to monitor bacterial releases and surface contamination. The data collected from this initial evaluation document that indicator bacteria were released from the unit. Modifications to the design and operation of a compactor of this type are proposed as suggestions that may improve system performance with regard to the health and safety of workers. A critical review of the experimental procedure used in this study is also included for the benefit of any future studies. PMID- 1609746 TI - Toward standardized training of physicians in clinical nutrition. PMID- 1609747 TI - Arachidonic acid concentrations in plasma and liver phospholipid and cholesterol esters of piglets raised on formulas with different linoleic and linolenic acid contents. AB - The influence of sow milk or infant formulas containing 18:2n-6 and 18:3n-3 (% fatty acids) at 30/1, 16/1, 35/4, or 16/4 on plasma and liver phospholipid (PL) and cholesterol ester (CE) arachidonic acid (20:4n-6) was studied in piglets fed from birth for 15 d. Piglets fed the 35/4, 16/1, and 16/4 formulas had a significantly lower percentage of plasma 20:4n-6 in PL than did piglets fed sow milk or the 30/1 formula. The lowest plasma PL 20:4n-6 was in the 16/4 group, the only group in which liver PL 20:4n-6 was significantly reduced. This suggests competitive inhibition of synthesis or acylation of 20:4n-6 when formula with a high content of 18:3n-3 is fed in conjunction with a low content of 18:2n-6. The percentage of plasma CE 20:4n-6 was not altered by formula feeding. In contrast, the liver CE 20:4n-6 was significantly lower in all formula-fed animals than it was in sow-milk-fed animals. These studies confirm that 20:4n-6 metabolism is altered in artificially fed neonates. Liver and plasma cholesterol concentrations were also significantly lower in all formula-fed than in milk-fed piglets. The potential relationship of the decrease in cholesterol to n-6 fatty acids in CE is unknown. PMID- 1609748 TI - Measurement of resistant starch: factors affecting the amount of starch escaping digestion in vitro. AB - We developed an in vitro assay system that mimics the physiological conditions for starch digestion. In this system all undigested starch was termed resistant starch (RS). The richest sources of RS were firm bananas and roasted chickpeas. Different food-processing techniques produced different amounts of RS. RS in uncooked oats (0.161 g/g dry wt) and firm bananas (0.247 g/g dry wt) was reduced by cooking to 0.028 and 0.032 g/g dry wt, respectively. Cooling boiled potato overnight at 4 degrees C produced a 2.8-fold increase in the amounts of RS. Whole rice contained more RS than did ground rice whereas grinding did not affect amounts of RS in roasted chickpeas. Amounts of RS in food decreased with increased chewing, indicating that chewing can also affect the amount of starch escaping digestion. This assay may be useful in predicting which foods and processing techniques result in high amounts of starch escaping digestion in the small intestine. PMID- 1609749 TI - Distribution of orally administered beta-carotene among lipoproteins in healthy men. AB - Plasma and lipoprotein concentrations of beta-carotene (BC) were measured in men for 10 d after an oral dose of BC (120 mg) (experimental subjects, n = 11) or no BC (control subjects, n = 5). Lipoproteins were separated by sequential ultracentrifugation and BC was measured by HPLC. Plasma and lipoprotein BC concentrations in control subjects were steady. In experimental subjects, plasma BC content increased by 6 h postdosing (P less than 0.015), peaked at 24 h (P less than 0.05), and returned to baseline by 7 d. Maintenance of plasma BC concentrations suggests homeostatic control. Of the 11 experimental subjects, only 4 had a plasma response. Early increases in the BC content of chylomicrons, very-low-density lipoproteins, and intermediate-density lipoproteins. Intestinal input accounts for early rises in circulating BC concentrations whereas hepatic secretion is the source of later increases. Among all of the lipoproteins, transfer of BC may occur. PMID- 1609750 TI - Mothers' and children's intakes of vitamin A in rural Bangladesh. AB - The vitamin A intake of 370 mothers and 183 children 3-27 mo of age in rural Bangladesh was ascertained monthly from January to July in 1986. For mothers, dark green leafy vegetables and fruits were the main sources of vitamin A. Vitamin A from vegetables, the single most important source, did not show consistent associations with wealth or with the other socioeconomic indicators. In May and June, fruits provided wealthier (and more educated) mothers with significantly higher vitamin A intakes than poor mothers, whereas in January the poorer mothers had higher intakes. When breast milk was included, average intakes for children came close to 100% of the recommended dietary allowance; the only other significant source of vitamin A for children was seasonally available mangoes. Fourteen children who had stopped breast-feeding by the end of the study were at very high risk of vitamin A deficiency when fruits were not plentiful. PMID- 1609751 TI - Body mass index from childhood to middle age: a 50-y follow-up. AB - The tracking of body mass index (BMI) over a 50-y period in a longitudinal study was examined by using both correlation coefficients and the Foulkes-Davis tracking index. Over the long term, BMIs before maturity were poor predictors of middle-aged BMI status in females but were good predictors in males. The correlation between females' BMI in childhood and their BMIs at two points during middle age (40 and 50 y) was zero; in males it was r = 0.36 and 0.41, respectively. Between-age correlations were high (P less than 0.0001) for both sexes, reflecting stability in BMI over the shorter term (less than or equal to 10 y). The tracking of BMI (with the Foulkes-Davis tracking index) from childhood to middle age was better for males than for females (P less than 0.1). Linear regression analysis was also used to assess the predictability of relative body size in middle age from earlier measures; BMI in childhood accounted for 0% of the variance in females and 17% in males. We conclude that the prediction of ponderosity in middle age from BMIs early in life is more reliable for males than for females. PMID- 1609752 TI - Effects of dietary zinc depletion on seminal volume and zinc loss, serum testosterone concentrations, and sperm morphology in young men. AB - Identification of the andrological variables most sensitive to zinc depletion would expedite the diagnosis of male reproductive pathology induced by zinc deficiency. Eleven volunteers living on a metabolic ward were fed a diet composed of a mixture of a semisynthetic formula and conventional foods supplemented with ZnSO4 to supply a total of 1.4, 2.5, 3.4, 4.4, or 10.4 mg Zn/d. After an equilibration period of 28 d (10.4 mg Zn/d), all treatments were presented for 35 d each, the first four in random order and the fifth last. Compared with when they were consuming 10.4 mg Zn/d, volunteers consuming 1.4 mg Zn/d exhibited decreased semen volumes (3.30 vs 2.24 mL) and serum testosterone concentrations (26.9 vs 21.9 nmol/L), and no change in seminal zinc concentrations. Compared with 10.4 mg Zn/d, treatments of 1.4, 2.5, and 3.4 mg Zn/d decreased the total semen zinc loss per ejaculate (6.29 vs 3.81, 4.68, and 5.03 mumols/ejaculate). Seminal loss accounted for 9% of total body zinc loss when 1.4 mg Zn/d was consumed. Seminal phosphorus concentrations were elevated during all four phases of zinc depletion (28.4 vs 32.9, 31.0, 34.2, and 33.6 mmol/L). The findings suggest that serum testosterone concentrations, seminal volume, and total seminal zinc loss per ejaculate are sensitive to short-term zinc depletion in young men. PMID- 1609753 TI - Nutritional support in children with end-stage liver disease: a randomized crossover trial of a branched-chain amino acid supplement. AB - Malnutrition is common in children with end-stage liver disease (ESLD) awaiting orthotopic liver transplantation (OLT), and nutritional support is assuming an important role in preoperative management. To evaluate preoperative nutritional therapy, 19 children (median age 1.25 y) with ESLD awaiting OLT were prospectively studied. Two high-energy, isoenergetic and isonitrogenous nutritional formulations delivered nasogastrically were compared: a branched chain amino acid (BCAA)-enriched semielemental formulation and a matched standard semielemental formation. Twelve of 19 patients completed a randomized controlled study before OLT and 10 of 19 completed a full crossover study. Improvements in weight and height occurred during the BCAA supplements, with no statistical change on the standard formulation. Significant increases in total body potassium, midupper arm circumference, and subscapular skinfold thickness occurred during the BCAA supplements, whereas no significant changes occurred during the standard formulation period. Significantly fewer albumin infusions were required during the BCAA supplement. These findings suggest that BCAA enriched formulas have advantages over standard semielemental formulas in improving nutritional status in children with ESLD, and are deserving of wider application and study. PMID- 1609754 TI - The nature of malnutrition in children with end-stage liver disease awaiting orthotopic liver transplantation. AB - To evaluate malnutrition in chronic liver disease, and its relationship to nutrient deficiencies and hepatic dysfunction, 27 children with end-stage liver disease were studied. Mean protein-energy intakes were 70% of recommended daily intakes. The patients were underweight and stunted with reduced mean triceps and subscapular skinfold thicknesses and midupper arm circumference. Mean total body potassium was only 63 +/- 18% of that expected for age and sex. Deficiency of essential fatty acids (32%), and low concentrations of fat-soluble vitamins (A, 92%; E, 32%), iron (32%), zinc (42%), and selenium (13%) were common. Serum ammonia concentrations were raised in all patients, and increased methionine, tyrosine, and glutamic acid, and reduced glutamine concentrations were noted. There was no correlation between the degree of malnutrition and the degree of liver synthetic function, the degree of cholestasis, or the degree of liver injury. We suggest that potentially correctable factors in addition to liver failure (eg, inadequate absorbed intake) were important determinants of malnutrition in these patients. PMID- 1609755 TI - Influence of dietary protein on glomerular filtration and urinary albumin excretion in insulin-dependent diabetes. AB - We investigated the effects of dietary constituents on glomerular filtration (GFR) and albumin excretion rates (AERs) in a cross-sectional study in 39 young subjects with insulin-dependent diabetes. Dietary protein intake correlated significantly in patients with GFRs less than 150 mL/min per 1.73 m2 (r = 0.53, n = 23, P = 0.009), but not with AER. GFR also correlated with mean blood glucose at a concentration less than 12.0 mmol/L (r = 0.61, P = 0.0035). Protein and fat intakes were similar in patients with and without microalbuminuria (AER greater than 20 mg/L) but long-term glycemic control was worse in the former [HbA1 12.4 +/- 2.9% (mean +/- SD) and 10.6 +/- 2.1%, respectively, P = 0.043]. In seven patients, short-term reduction of dietary protein from 2.0 to 1.0 to 0.5 g.kg-1.d 1 produced a progressive fall in GFR by 11.6 +/- 6.0 and 9.6 +/- 5.9 mL/min, respectively (P less than 0.05), but did not consistently affect AER. We conclude that both dietary protein and glycemic control influence GFR but neither alone appears to explain glomerular hyperfiltration. Microalbuminuria was associated with poor glycemic control but not with dietary fat or protein consumption. PMID- 1609756 TI - The five-level model: a new approach to organizing body-composition research. AB - Body-composition research is a branch of human biology that has three interconnecting areas: body-composition levels and their organizational rules, measurement techniques, and biological factors that influence body composition. In the first area, which is inadequately formulated at present, five levels of increasing complexity are proposed: I, atomic; II, molecular; III, cellular; IV, tissue-system; and V, whole body. Although each level and its multiple compartments are distinct, biochemical and physiological connections exist such that the model is consistent and functions as a whole. The model also provides the opportunity to clearly define the concept of a body composition steady state in which quantitative associations exist over a specified time interval between compartments at the same or different levels. Finally, the five-level model provides a matrix for creating explicit body-composition equations, reveals gaps in the study of human body composition, and suggests important new research areas. PMID- 1609758 TI - Human dietary responses to covert manipulations of energy, fat, and carbohydrate in a midday meal. AB - Dietary responses to dilution or supplementation of the energy value and macronutrient content of foods are poorly characterized in humans. After a 1-wk baseline, 16 free-living, normal-weight adults were provided midday meals systematically varying in energy, fat, and carbohydrate contents for 5-d periods. Their compensatory free-feeding intake was monitored through diet records. In response to energy dilution by carbohydrate or fat, mean daily energy intake was 88% and 97% of baseline, respectively. Responses to the energy surfeit led to intakes 104% and 116% of baseline, respectively. However, the absolute magnitude of the carbohydrate supplement challenge was small. Adjustments of macronutrient specific intake during the high-carbohydrate, low-carbohydrate, high-fat, and low fat meal periods were 134%, 91%, 165%, and 95% of baseline, respectively. Although these group findings indicate that defense against covert dilution of the energy, fat, or carbohydrate contents of a meal is stronger than that to supplementation, individual responses were highly variable. PMID- 1609757 TI - Validation of estimates of energy intake by weighed dietary record and diet history in children and adolescents. AB - Energy intakes assessed by 7-d weighted dietary records (EI-WDRs) and diet histories (EI-DHs) were compared with concurrent estimates of total energy expenditure (TEE) by the doubly labeled water method in 78 subjects aged 3-18 y. EI-WDRs were not obtained from the 3- and 5-y-old subjects. EI-WDRs in the 7- and 9-y-old children were 108 +/- 25% (n = 12) and 97 +/- 15% (n = 12), respectively, of corresponding TEE values showing good agreement. However in the 12-, 15-, and 18-y-old subjects EI-WDR averaged 89 +/- 12% (n = 12), 78 +/- 18% (n = 12), and 73 +/- 25% (n = 10), respectively, of corresponding TEE values. The difference was greater than or equal to 20% in 13 adolescents. Mean EI-DHs were 114 +/- 19% (3 y), 111 +/- 19% (5 y), 111 +/- 23% (7 y), 106 +/- 9% (9 y), 114 +/- 17% (12 y), 101 +/- 21% (15 y), and 98 +/- 21% (18 y) of TEE estimates. Differences were significant in the 3-, 9-, and 12-y-old subjects. Results suggest that 7-d EI WDRs tend to underestimate food intake of adolescents. Although EI-DHs were biased towards overestimation in most age groups and individual measurements lacked precision, EI-DHs were more representative of habitual intake than were EI WDRs. PMID- 1609759 TI - Is bioimpedance a good predictor of body-composition change? PMID- 1609760 TI - Lipid and insulin concentrations in obese postmenopausal women: separate effects of energy restriction and weight loss. AB - The separate effects of energy restriction and weight loss on serum lipids were studied in 24 postmenopausal moderately obese women before and after weight loss of greater than 10 kg to normal weight. Fasting serum triglycerides (TGs), total cholesterol (TC), high-density-lipoprotein (HDL) and low-density-lipoprotein (LDL) cholesterol, and insulin were measured at the end of four 10-d in-hospital phases, two before and two after weight loss: phase I, stable weight; phase II, 3350 kJ/d(800 kcal/d), followed by outpatient weight loss; phase III, 3350 kJ/d (800 kcal/d); and phase IV, stable weight. Diet composition and exercise were constant the entire study. Energy-restriction effect was determined by comparing average values in stable-weight phases (I and IV) with low-energy phases (II and III); weight-loss effect was determined by comparing values in obese phases (I and II) with reduced-weight phases (III and IV). Energy restriction lowered TG, TC, LDL cholesterol, the LDL-HDL cholesterol ratio, and insulin and raised HDL cholesterol (all P less than 0.05). Weight loss lowered TG, TC, LDL cholesterol, and insulin (all P less than 0.01) but did not change HDL cholesterol or the LDL HDL cholesterol ratio. The results suggest that reduction to a weight-steady nonobese state significantly lowers TG, TC, and LDL cholesterol but does not improve HDL cholesterol or the LDL-HDL cholesterol ratio. PMID- 1609762 TI - Potential for misclassification of infants' growth increments by using existing reference data. AB - The observed variances in monthly weight and length gains of 96 Peruvian infants were compared with predicted variances obtained by applying the reference curve fitting methods to the same Peruvian data. Predicted variance estimates were significantly less (P less than 0.0001) than the observed variances from 2 to 12 mo of age. The extent of underestimation in total variance that occurred when 1 mo growth-increment reference data were generated by curve-fitting and interpolation was approximated. This underestimation, caused by not taking into account infants' random deviations from their own growth trajectories, ranged from 59% to 94% and resulted in misclassification of approximately 24-67% of infants as abnormal gainers (below the 5th percentile or above the 95th percentile with respect to existing reference data) in the intervals evaluated. PMID- 1609761 TI - Effect of vitamin A and zinc supplementation on the nutriture of children in Northeast Thailand. AB - Previous surveys suggested that young children in Northeast Thailand may benefit from vitamin A and/or zinc supplementation. One hundred thirty-three children aged 6-13 y with marginal plasma retinol (less than 1.05 mumol/L) and Zn (less than 12.2 mumol/L) concentrations participated in a double-blind study. They were randomly assigned and supplemented with either zinc (25 mg/d), vitamin A (1500 RE/d), zinc plus vitamin A, or placebo for 6 mo. Biochemical indices of vitamin A (plasma vitamin A, retinol-binding protein) and zinc status (plasma zinc, alkaline phosphatase) increased significantly. The children had adequate liver stores of vitamin A (relative dose response less than 20%). Zinc supplementation resulted in an improvement in vision restoration time (VRT) in dim light (dark adaptometry). Vitamin A and zinc synergistically normalized conjunctival epithelium as measured by conjunctival impression cytology (CIC). Both functional indices, VRT and CIC, showed significant correlations with plasma zinc and vitamin A, respectively. The data suggest that functional improvements in populations with suboptimal vitamin A and zinc nutriture can be accomplished by supplementation with less than two times the recommended dietary allowance of these nutrients. PMID- 1609763 TI - Milk and blood fatty acid composition during two lactations in the same woman. AB - Fatty acid composition of colostrum, milk, and serum was studied during two consecutive lactations in the same woman. There were marked differences between milk and serum: medium chain fatty acids (C6:0-C14:0) were higher in milk (8.36 21.37%) than in serum (1.59-9.6%) throughout lactation. The high milk-serum ratio of medium chain fatty acids (up to 28.4, 30.2, and 6.2 for 10:0, 12:0, and 14:0, respectively) indicates synthesis in the mammary gland. Long-chain polyunsaturated fatty acids (C20:1-C22:6) of the n - 3 and n - 6 series were higher in serum (6.76-12.53%) than in milk (1.57-4.42%). With the exception of colostrum, the fatty acid composition of milk and serum changed little during lactation and was similar in two consecutive lactations in the same woman. Comparison of milk and serum fatty acids provides a noninvasive approach for the assessment of the synthetic activity of the human mammary gland. PMID- 1609764 TI - Validation of the in vivo measurement of adipose tissue by magnetic resonance imaging of lean and obese pigs. AB - In vivo quantification of adipose tissue with magnetic resonance imaging (MRI) was validated with pigs. Thirteen transaxial MRI sections were collected, at intervals proportional to body length, from each pig, which was then killed, frozen, and sliced at the locations of the MRI sections. Adipose-tissue quantities were determined by dissecting each slice, and lipid contents of the dissected slices and of the tissue segments between slices were measured. Compared with dissection, MRI underestimated abdominal percent adipose tissue and overestimated cervical percent adipose tissue by less than 6%. When all 13 sections were used, MRI closely predicted percent lipid and dissected percent adipose tissue with small residual SDs (RSD = 1.9 and 2.1, respectively), which increased only slightly if two sections (4, upper thorax and 8, upper abdomen) were used (RSD = 2.3 and 2.6, respectively). In conclusion MRI accurately quantifies adipose tissue in vivo, matching values produced by dissection and chemical analysis. PMID- 1609765 TI - Effects of alterations in fatty acid intake on the blood pressure of adolescents: the Exeter-Andover Project. AB - To judge the effect on blood pressure, the ratio of polyunsaturated to saturated fatty acids (P:S) of foods served to students at two boarding high schools was modified alternately at each school for one school year. The average P:S of the diet of males increased from 0.53 to 0.93 during the intervention whereas among females it increased from 0.64 to 0.98. Comparison of repeated systolic and diastolic blood pressure measurements near the end of the school year did not demonstrate a beneficial effect of the dietary fat changes on the blood pressure of these normotensive adolescents. Compared with the blood pressure patterns during control years, the dietary intervention resulted in slightly higher systolic (+0.88 mm Hg; 95% CI -0.66, +2.42) and diastolic (+1.23 mm Hg; 95% CI = +0.04, +2.42) blood pressure readings among males. Among females the intervention resulted in slightly lower systolic (-0.54 mm Hg; 95% CI = -1.95, +0.88) and diastolic (-0.80 mm Hg (95% CI -2.18, +0.58) blood pressure readings. PMID- 1609766 TI - Effect of dietary monounsaturated fatty acids on plasma lipoproteins and apolipoproteins in women. AB - To determine the effects of dietary fat saturation on plasma lipoproteins, we studied 21 free-living normolipidemic women (13 pre- and 8 postmenopausal) on three consecutive diet periods. During the first 4 wk they consumed a saturated diet rich in palm oil and butter [19% saturated fatty acids (S), 14% monounsaturated fatty acids (M), and 3.5% polyunsaturated fatty acids (P)], followed by 6 wk of a monounsaturated diet rich in olive oil (11% S, 22% M, and 3.6% P), and 6 wk of a polyunsaturated diet rich in sunflower oil (10.7% S, 12.5% M, and 12.8% P). Compared with the diet rich in saturated fatty acids, both diets rich in unsaturated fatty acids had similar lowering effects on total and low density-lipoprotein cholesterol. High-density lipoprotein cholesterol and apolipoprotein A-I were higher in the monounsaturated-rich period than in the polyunsaturated-rich (10.5% and 12.7% respectively, P less than 0.001) and the saturated-rich period (5.3%, and 7.9%, respectively, P less than 0.05). These effects were independent of menopause status. Our data show that at this level of fat intake (36% as calories), a monounsaturated-rich diet results in a less atherogenic lipid profile than either polyunsaturated- or saturated-rich diets. PMID- 1609767 TI - Effects of olestra, a noncaloric fat substitute, on daily energy and fat intakes in lean men. AB - Nutrient and energy intakes, hunger, and fullness were examined after the replacement of 36, 20, or 0 g fat in breakfast with olestra, a noncaloric fat substitute. Twenty-four lean, nondieting men (aged 21-30 y) participated in a placebo-controlled, three-condition crossover design. Self-selected, ad libitum intakes at lunch and dinner were monitored in the laboratory. Evening snacks and breakfast the next day were assessed through food diaries. Visual-analog-scale ratings including hunger and fullness were collected throughout the test days. Single-meal olestra substitution produced a significant dose-related reduction in the amount and percentage of energy from fat consumed daily with a reciprocal increase in carbohydrate intake. Daily energy intakes were not significantly different nor did ratings of hunger and fullness vary systematically between conditions. Consumption of olestra can reduce fat intake and increase carbohydrate intake without affecting total daily energy intake or usual patterns of hunger and fullness. PMID- 1609768 TI - Bound vitamin B12 absorption in patients with low serum B12 levels. AB - In many patients with low serum levels of vitamin B12, the absorption of the free vitamin has been normal. The present study, using a total body counter 57CoB12 absorption method that clearly separated those with intrinsic factor deficiency from controls, found that of 94 patients with low B12 levels and intact stomachs in whom the absorption of free and bound B12 was determined, 44 (47%) had normal absorption of both. However, 20 of the 94 (21%) with normal absorption of free B12 had low absorption of bound B12. The remainder (32%) had low absorption of both free and bound B12. All patients with high serum gastrin levels had low bound B12 absorption, but so did 21% of those patients with normal serum gastrin levels. PMID- 1609769 TI - Plasma cytokine levels in thrombotic thrombocytopenic purpura. AB - Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Auto-antibodies, platelet-associated immunoglobulin G, and platelet aggregating factor were detected in many of these patients and high-molecular-weight bands of von Willebrand factor multimers were reduced in 9 of 10 patients examined. Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1 beta, IL-6, and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. These findings suggest that immunological mechanisms, such as the activation of macrophage, are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels. PMID- 1609770 TI - Clonality of cold agglutinins in patients with hemolytic anemia: an analysis by high-resolution two-dimensional gel electrophoresis. AB - High-resolution two-dimensional gel electrophoresis (2-DGE) was used to analyse plasma samples and partially purified cold agglutinins (CA) obtained from two selected patients. Both presented an acute hemolytic anemia with CA of high thermal amplitude, normal immunoglobulin levels, no detectable paraproteinemia, and no clinical evidence of a malignant B-cell disorder. The electrophoretograms of their plasma showed evident alternations of the "normal" protein profile, which were directly related to hemolysis (absence of the spots of haptoglobin and in one case of those of hemopexin), but no monoclonal gammopathy. The electrophoretograms of their purified CA revealed two clearly different spot patterns respectively corresponding to a monoclonal IgM and to polyclonal IgM. These results show that the clonality of CA associated with hemolytic anemia can be easily determined by 2-DGE. This technique may be very useful to discriminate chronic cold agglutinin disease in the early phase from "parainfectious" CA. PMID- 1609771 TI - Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HIV(+) hemophilic men. AB - The use of ibuprofen (IBP) in hemophilic men for chronic hemophilic arthropathy is associated with transient coagulation abnormalities, but usually does not cause bleeding symptoms. However, when hemophilic men are treated with ibuprofen while also receiving zidovudine (ZDV), excess bleeding has occurred in some. In order to evaluate platelet function and pharmacokinetics of combination IBP and ZDV, we measured platelet aggregation, platelet adhesive index, bleeding time, and IBP and ZDV drug levels by high performance liquid chromatography on five patients receiving chronic oral IBP, 400 mg every 6 hr, and on ten patients receiving both IBP and ZDV, 100 or 200 mg every 4 hr five times daily. Samples were obtained at baseline (ZDV alone), acutely (IBP+ZDV acutely), and chronically (2 weeks on IBP and ZDV). Abnormal platelet aggregation with arachidonic acid occurred in four of five (80%) of those receiving IBP alone and in 7 of 10 (70%) at baseline, 9 of 10 (90%) at acute, and 8 of 10 (80%) at chronic IBP and ZDV treatment, most commonly at 2 hr following dosing, when peak IBP levels occurred, and persisting 4 hr in those on chronic dosing. Half or more of those on combination IBP+ZDV showed a lowered platelet adhesive index and/or prolonged bleeding time. Excess bleeding symptoms occurred in three on chronic combination IBP+ZDV, two with increased frequency of spontaneous hemorrhages, and one with prolonged traumatic bleeding. Bleeding tendency was unrelated to the degree of platelet function abnormality, to peak drug levels of IBP or ZDV, or degree of liver function abnormality (SGPT). The clearance of IBP alone and ZDV alone were not different from the clearance of combination IBP and ZDV. Caution is urged regarding potential enhanced bleeding tendency in hemophiliacs receiving both IBP and ZDV in combination. PMID- 1609772 TI - Morphologic characteristics of acute lymphoblastic leukemia (ALL) with abnormalities of chromosome 8, band q24. AB - The CALGB prospectively studied 140 adult acute lymphoblastic leukemia (ALL) patients for cytogenetic abnormalities. Seven (5%) patients with adequate cytogenetic preparations had t(8;14)(q24;q32) or t(8;22)(q24;q11). Patients were compared with non-8q24 patients for clinical and laboratory characteristics, response to therapy, and survival. The median age of patients with translocations involving 8q24 (71% males) was 40 years. Forty-three percent had lymphadenopathy, 29% splenomegaly, and 29% hepatomegaly. None exhibited central nervous system (CNS), skin, or gum involvement. These features did not differ significantly from non-8q24 ALLs. Patients with 8q24 translocations had higher hemoglobins (11.5 vs. 9.8 g/dl; P = 0.04) and lower percentage of blasts in the peripheral blood (8.5% vs. 69%; P = 0.007). Although all seven were finally categorized as ALL-L3, a marked variation in the proportion of typical L3 blasts was observed that initially resulted in the diagnoses of ALL-L2 in three cases and prolymphocytic leukemia in one. In five of five patients, the blasts typed as B cells (SIg+ and CD19+). Complete remission rates for patients with 8q24 translocations were 43%, whereas they were 68% for non-8q24 ALLS (P = 0.22). Furthermore, patients with 8q24 abnormalities exhibited significantly shorter survival (4.8 vs. 18.4 mo; P less than 0.001). We conclude that ALL with translocations of 8q24 in adults shows a mature B-cell immunophenotype (SIg+), poor prognosis and morphology ranging from classical ALL-L3 to ALL with a subpopulation of L3 cells. Thus, the diagnosis of ALL-L3 should be made when blastic cells possess a mature B-cell immunophenotype (SIg+) and an 8q24 translocation, even though the number of L3 cells is low. PMID- 1609773 TI - A probable double heterozygous type II von Willebrand's disease with increased ristocetin induced platelet aggregation. AB - We have identified a patient with von Willebrand's disease (vWD) resembling type IIB vWD, with increased ristocetin induced platelet aggregation (RIPA), the absence of the large multimers of von Willebrand factor (vWF) in plasma, and the presence of the large multimers in platelets in whom a family study indicated a probable double heterozygous inheritance pattern. The propositus was a 12-year old boy with frequent epistaxis and bruising. Abnormal hemostatic findings included a prolonged bleeding time (BT), decreased levels of factor VIII coagulant activity (VIIIC), von Willebrand factor antigen (vWF:Ag), ristocetin cofactor (RCof), and an increased RIPA. In the presence of ristocetin, binding of the patient's plasma vWF to normal platelets was increased but binding of normal vWF to his platelets was normal. SDS-agarose gel (1.5%) electrophoresis revealed that plasma vWF lacked the large multimers, and 3.0% gel electrophoresis revealed that the multimers had a 5-band pattern similar to normal. The above findings were consistent with type IIB vWD, but 1-deamino[8-D-arginine]-vasopressin (DDAVP) infusion resulted in a shortened BT and the transient appearance of large multimers without a decrease in the platelet count. Family studies revealed that his mother has mild bleeding symptoms, decreased VIIIC, vWF:Ag, and RCof levels and normal to slightly reduced RIPA with a multimer pattern consistent with type I vWD. In contrast, the father, sister, and paternal grandfather were asymptomatic, with a slightly decreased VIIIC level but a normal BT and vWF:Ag and RCof levels. Their RIPA and vWF binding to normal platelets were increased, but unlike the propositus their plasma contained large multimers. We concluded that the propositus is a type IIB-like variant differing from previously reported IIB variants in two ways: 1) his response to DDAVP and 2) a possible double heterozygous mode of inheritance rather than the usual dominant route. PMID- 1609774 TI - Role of splenectomy in the management of hemophilic patients with human immunodeficiency virus-associated immunopathic thrombocytopenic purpura. AB - Immunopathic thrombocytopenic purpura (ITP) can be a life-threatening complication of human immunodeficiency virus (HIV) infection in patients with hemophilia and can seriously compromise quality of life if not managed effectively. We report here complete response to splenectomy in four severe hemophiliacs with HIV-associated ITP. All patients were symptomatic, had platelet counts less than 25,000/mm3, and had failed at least one non-surgical therapy prior to splenectomy. All patients tolerated surgery well and obtained an immediate and durable complete response. In addition to our experience, a review of the literature shows that splenectomy is well tolerated and provides the most effective long-term solution for hemophiliacs with HIV-ITP. PMID- 1609775 TI - Coagulation factor IX: successful surgical experience with a purified factor IX concentrate. AB - The use of plasma-derived coagulation factor concentrates has been marked by the transmission of viral agents. Infusions of factor IX complex concentrates have been additionally complicated by inappropriate thrombosis. Use of these concentrates in the neonate, in those with liver disease, and in surgical patients results in increased risk for this complication. Twenty patients have been infused with a purified coagulation factor IX concentrate for fall-off and recovery studies. A two-compartment model indicated an initial phase half-life of 4.06 +/- 2.86 hr and a beta phase half-life of 20.0 +/- 3.8 hr following the administration of AlphaNine, Coagulation Factor IX (Human). In vivo recovery was 62.7% +/- 13.8%, with an average factor IX coagulant level of 73% +/- 16% at 15 min after the infusion of a mean dose of 45 U/kg. Thirteen previously transfused patients with hemophilia B underwent major orthopedic or general or dental surgery using this purified factor IX. Operative outcomes were excellent in all patients. No excessive bleeding was noted. There was no laboratory or clinical evidence for a disseminated intravascular coagulopathy. The excellent surgical outcomes observed in this multitransfused group with biochemical evidence for active liver disease demonstrates the utility and safety of a purified coagulation factor IX concentrate. PMID- 1609776 TI - Spontaneous remission of multilobated non-Hodgkin lymphoma. AB - A 67-year-old previously well man was admitted with hypercalcemia after a 7-day history of fever, night sweats, and back pain. The blood showed 5% multilobated lymphoid cells. A multilobated non-Hodgkin lymphoma associated with marked reticulin fibrosis was diagnosed on a bone marrow biopsy. During the next 7 days, in the absence of specific therapy, his symptoms disappeared. Three weeks after admission his biochemical abnormalities had resolved and after 9 weeks his bone marrow examination was normal. He remains in clinical and laboratory remission 16 months after presentation. PMID- 1609777 TI - Ifosfamide in plasma cell leukemia: a report of two cases and review of the literature. AB - We report two patients with primary plasma cell leukemia (PLC) treated with a single agent, ifosfamide. One patient had a total disappearance of plasma cells (PC) from the peripheral blood and the bone marrow and disappearance of the myeloma protein, is disease free 8 months after completion of treatment, and alive 14 months after diagnosis. The second patient had a partial response with persistence of plasma cells in the bone marrow lasting 7 months, after which she had a frank relapse of the disease. We suggest that ifosfamide may be an active agent in plasma cell malignancies and needs further evaluation in multiple myeloma. PMID- 1609778 TI - Clonal remission in aplastic anemia after treatment with antithymocyte globulin. AB - Aplastic anemia includes a group of disorders characterized by peripheral blood pancytopenia and marrow hypocellularity. The current report describes a patient who is an apparent constitutional mosaic and presented with marrow aplasia. Using cytogenetic analysis of bone marrow, skin, and peripheral T lymphocytes, we demonstrated the clonal nature of this patient's aplastic marrow, and, in addition, identify clonal evolution. The patient was treated with antithymocyte globulin (ATG) and achieved a complete remission, with disappearance of an abnormal evolved clone. This case illustrates that clonal cytogenetic abnormalities do not preclude a response to ATG and that aplastic anemia may be a nonmalignant clonal disorder with clonal evolution. PMID- 1609779 TI - Secondary T-cell lymphoma in the setting of nodular lymphocyte predominance Hodgkin's disease. AB - Lymphocyte predominance Hodgkin's disease (LPHD) can be histologically subdivided into a nodular and diffuse variety. The two subtypes differ in immunophenotypic characteristics but have a similar long-term clinical outcome. Nodular LPHD has immunophenotypic and histological characteristics suggestive of a B-cell derived neoplastic process. Nodular LPHD is associated with an increased risk of secondary large cell lymphoma (LCL). Gene rearrangement studies in some of these cases have revealed a B-cell clonal process, further supporting the association between nodular LPHD and the B-cell system. In addition, it has been suggested that the apparent secondary LCL, at least in some cases, may represent a histologic progression of nodular LPHD. We report a unique case of T-cell lymphoma, confirmed by T-cell receptor gene rearrangement studies, which developed in the setting of nodular LPHD. Our observation demonstrates that the association of nodular LPHD and LCL is complex and that LCL developing in the context of nodular LPHD may be an independent secondary process sometimes involving T-cell lymphomas. PMID- 1609780 TI - Possible interactions between warfarin and 5-fluorouracil. PMID- 1609781 TI - Successful pregnancy and delivery during alpha-interferon therapy for chronic myeloid leukemia. PMID- 1609782 TI - HLA-DR2 predicts a favorable response to cyclosporine therapy in patients with bone marrow failure. PMID- 1609783 TI - Transient hypoplastic anemia of childhood. PMID- 1609784 TI - Porphyria cutanea tarda associated with acute non-lymphoblastic leukemia. PMID- 1609785 TI - Fatal acute cardiomyopathy associated with "non-cardiotoxic" chemotherapy for autologous bone marrow transplantation. PMID- 1609786 TI - Dermatomyositis associated with acute promyelocytic leukemia. PMID- 1609787 TI - Five monoclonal proteins in a patient with chronic myelomonocytic leukemia. PMID- 1609788 TI - The Human Genome Project: where did it come from, where is it going? PMID- 1609789 TI - Anticipation in myotonic dystrophy: new light on an old problem. AB - The concept of anticipation, the occurrence of a genetic disorder at progressively earlier ages in successive generations, has been debated from the early years of this century, with myotonic dystrophy as the most striking example. Throughout most of this period there has been controversy as to whether the phenomenon resulted from observational and ascertainment biases or reflected a more fundamental mechanism. The recent discovery of inherited unstable DNA sequences, first in fragile-X mental retardation and now in myotonic dystrophy, not only confirms that anticipation indeed has a true biological basis but provides a specific molecular mechanism for it; this discovery can explain many of the puzzling anomalies in the inheritance of myotonic dystrophy and may prove relevant to comparable problems in other genetic disorders. PMID- 1609790 TI - The magnitude and origin of European-American admixture in the Gila River Indian Community of Arizona: a union of genetics and demography. AB - Complementary genetic and demographic analyses estimate the total proportion of European-American admixture in the Gila River Indian Community and trace its mode of entry. Among the 9,616 residents in the sample, 2,015 persons claim only partial Native American heritage. A procedure employing 23 alleles or haplotypes at eight loci was used to estimate the proportion of European-American admixture, m(a), for the entire sample and within six categories of Caucasian admixture calculated from demographic data, md. The genetic analysis gave an estimate of total European-American admixture in the community of 0.054 (95% confidence interval [CI] .044-.063), while an estimate from demographic records was similar, .059. Regression of m(a) on md yielded a fitted line m(a) = .922md, r = .959 (P = .0001). When total European-American admixture is partitioned between the contributing populations, Mexican-Americans have provided .671, European Americans .305, and African-Americans .023. These results are discussed within the context of the ethnic composition of the Gila River Indian Community, the assumptions underlying the methods, and the potential that demographic data have for enriching genetic measurements of human admixture. It is concluded that, despite the severe assumptions of the mathematical methods, accurate, reliable estimates of genetic admixture are possible from allele and haplotype frequencies, even when there is little demographic information for the population. PMID- 1609791 TI - Prenatal diagnosis of Niemann-Pick type C disease: current strategy from an experience of 37 pregnancies at risk. AB - Thirty-seven pregnancies at risk for Niemann-Pick type C disease were monitored by study of cultured amniotic fluid cells (8 cases) or chorionic villus cells (29 cases) in 23 couples over the period 1984-91. An early protocol combined determination of sphingomyelinase activity with electron microscopy. The current strategy, based on the demonstration of specific abnormalities in intracellular processing of exogenous cholesterol, combines the study of the early phase (first 6 h) of LDL-induced cholesteryl ester formation and the histochemical evaluation (filipin staining after 24 h of LDL uptake) of the LDL-induced accumulation of unesterified cholesterol. Thirteen fetuses were predicted to be affected. Confirmation of the diagnosis was made by study of cholesterol processing in fetal skin fibroblast cultures and/or by demonstration of a characteristic lipid storage in fetal liver, already present at 14 w gestation. Definition of the biochemical phenotype (classical, variant, or intermediate) of the index case, with regard to cholesterol-processing abnormalities, is an absolute prerequisite to adequate genetic counseling in a given family. Prenatal diagnosis has now proved a safe procedure in the predominant (approximately 85%) group of families with the classical phenotype. PMID- 1609792 TI - A large deletion in the LDL receptor gene--the cause of familial hypercholesterolemia in three Italian families: a study that dates back to the 17th century (FH-Pavia). AB - In the LDL-receptor gene, a large rearrangement causing hypercholesterolemia was detected in three apparently unrelated families living in northern Italy. In all probands, binding, internalization, and degradation of 125I-LDL measured in skin fibroblasts were found to be 40%-50% of control values, indicative of heterozygous familial hypercholesterolemia (FH). Southern blot analysis revealed that the probands were heterozygous for a large (25-kb) deletion of the LDL receptor gene eliminating exons 2-12. The affected subjects possessed two LDL receptor mRNA species: one of normal size (5.3 kb) and one of smaller size (3.5 kb). In the latter mRNA, the coding sequence of exon 1 is joined to the coding sequence of exon 13, causing a change in the reading frame and thereby giving rise to a premature stop codon. The receptor protein deduced from the sequence of the defective mRNA is a short polypeptide of 29 amino acids, devoid of any function. Tracing these three families back to the 17th century, we found both their common ancestor and the possible origin of the mutation, in a region which is called "Lomellina" and which is located in southwest Lombardy, near the old city of Pavia. Therefore we named the mutation "FH-Pavia." PMID- 1609793 TI - Replacement of arginine 773 by cysteine or histidine in the human androgen receptor causes complete androgen insensitivity with different receptor phenotypes. AB - We have discovered two different point mutations in a single codon of the X linked androgen-receptor (AR) gene in two pairs of unrelated families who have complete androgen insensitivity (resistance) associated with different AR phenotypes in their genital skin fibroblasts. One mutation is a C-to-T transition at a CpG sequence near the 5' terminus of exon 6; it changes the sense of codon 773 from arginine to cysteine, ablates specific androgen-binding activity at 37 degrees C, and eliminates a unique KpnI site at the intron-exon boundary. The other mutation is a G-to-A transition that changes amino acid 773 to histidine and eliminates an SphI site. This mutant AR has a normal androgen-binding capacity at 37 degrees C but has a reduced affinity for androgens and is thermolabile in their presence. Transient transfection of COS cells with cDNA expression vectors yielded little androgen-binding activity at 37 degrees C from Arg773Cys and abundant activity with abnormal properties from Arg773His, thereby providing the pathogenicity of both sequence alterations. This conclusion coincides with the following facts about evolutionary preservation of the position homologous to Arg773 in the AR: it is occupied by Arg or lysine in the progesterone, glucocorticoid, and mineralocorticoid receptors, and it is within a 14-amino-acid region of their steroid-binding domains that share approximately 85% amino acid identity. PMID- 1609794 TI - Chromosome bands, their chromatin flavors, and their functional features. AB - To show that the input pattern of chromosomal mutations is highly organized relative to the band patterns along human chromosomes, a new term, "metaphase chromatin flavor," is introduced. Five different flavors of euchromatic metaphase bands are cytologically identified along a human ideogram. These are G-bands and, based upon combinations of extreme Alu richness and GC richness, four different R band flavors. The two flavors with extremely GC-rich components, traditionally called "T-bands," represent only 15% of all bands. However, they contain 65% of mapped genes, 19 of 25 mapped oncogenes, most cancer-associated rearrangements, evolutionary rearrangements, meiotic chiasmata, and X-ray-induced breaks. Flavors with extremely Alu-rich flavors are also involved in melphalan-induced rearrangements, pachytene stretching, and mitotic chiasmata. Frequencies of CpG islands, CCGCCC boxes, retroposon families, and genes are characteristic to each chromatin flavor and will facilitate alignment of genome sequences onto ideograms of chromatin flavor. The influence of chromatin flavor on the evolution of a gene's sequence is so strong that one can infer the flavor of the band in which a gene resides from the sequence of the gene itself. Correlation coefficients for many pairs of mapped genetic variables, while globally high, are quite low within bands of one flavor, implicating a concerted mode of evolution for bands of one chromatin flavor. PMID- 1609795 TI - The human gene encoding acetylcholinesterase is located on the long arm of chromosome 7. AB - Acetylcholinesterase (AChE) is a secreted enzyme essential for regulating cholinergic neurotransmission at neuronal and neuromuscular synapses. In view of the altered expression of AChE in some central neurological and neuromuscular disorders with a probable genetic basis, we have identified the chromosomal location of the gene encoding AChE. Chromosomal in situ suppression hybridization analysis revealed a single gene to be at 7q22, a result which was confirmed by PCR analysis of genomic DNA from a human/hamster somatic cell hybrid containing a single human chromosome 7. The AChE gene thus maps to the same region in which frequent nonrandom chromosome 7 deletions occur in leukemias of myeloid cell precursors known to express the enzyme during normal differentiation. PMID- 1609796 TI - A method for assessing patterns of familial resemblance in complex human pedigrees, with an application to the nevus-count data in Utah kindreds. AB - An analytic method is described for estimating phenotypic correlations between pairs of members of specific relationships in pedigrees. In estimating correlations, this new method allows simultaneous adjustment for available covariates such as age, gender, environmental factors, and variables reflecting ascertainment mode, through mean- and variance-regression models. The estimated correlations and regression coefficients corresponding to covariates are consistent and asymptotically normally distributed. Differing from a full likelihood approach, this new method does not require the assumption of a particular joint distribution of phenotypes from a pedigree, such as the multivariate normal distribution, but instead only requires correct specification of mean- and variance-regression models. Within this framework, missing data, if they are missing completely at random, can be ignored without biasing estimates. The method is illustrated by an application using nevus-count data from 28 Utah kinships. The results from the analysis are that covariate-adjusted nevus counts are correlated between parents and children (correlation .22; P less than .001) and between siblings (correlation .32; P less than .001), while the correlation of -.04 between husband and wife is not significantly different (P = .31) from 0. This result is consistent with a genetic etiology of nevus count. PMID- 1609797 TI - Time and space clusters of the French-Canadian M1V phenylketonuria mutation in France. AB - We performed mutation analysis and RFLP haplotype analysis of chromosomes associated with classical phenylketonuria (PKU) in contemporary French families. We also did genealogical reconstructions for seven obligate carriers in five contemporary French-Canadian families living in eastern Quebec, who carry the M1V mutation causing PKU. The M1V mutation, heretofore considered to be associated exclusively with French-Canadians, was found on 4 of 152 independent French chromosomes. The French and Quebec M1V mutations all occurred on RFLP haplotype 2. The contemporary mutant French chromosomes clustered in southern Brittany (Finistere Sud). Genealogical reconstructions of the Quebec families identified 53 shared ancestors and a center of diffusion in the Perche region in 17th century France. The two clusters in France, one historical and the other contemporary, are not incompatible, if one assumes the possibilities that settlers returned from Nouvelle France or moved from Perche to southern Brittany. The M1V mutation is serving as a useful marker for historical demography. PMID- 1609798 TI - Evidence for genetic factors for resistance/susceptibility to schistosome infection. PMID- 1609799 TI - Profiles in genetics: Archibald E. Garrod (1857-1936). PMID- 1609800 TI - Genetics Week in Delaware: a new concept in genetics education for health-care providers in the community. PMID- 1609801 TI - Historical review of eugenics. PMID- 1609802 TI - Common sequence motifs at the rearrangement sites of a constitutional X/autosome translocation and associated deletion. PMID- 1609803 TI - Microdeletions in patients with gusher-associated, X-linked mixed deafness (DFN3). AB - Employing various probes from the proximal part of the Xq21 region, which is known to harbor the DFN3 gene, we have investigated 13 unrelated male probands with X-linked deafness, to detect possible deletions. For two of these patients, microdeletions could be detected by using probe pHU16 (DXS26). One of these deletions also encompasses locus DXS169, indicating that it extends farther toward the centromere. The presence of normal hybridization patterns in the DNA of 25 unrelated control males suggests that these deletions are the primary cause of progressive mixed deafness in these patients. If so, their molecular characterization may pave the way for the identification and isolation of the corresponding gene. PMID- 1609804 TI - Cloning of a candidate gene for ataxia-telangiectasia group D. AB - Transfection, with a human cosmid clone library, of an ataxia-telangiectasia (AT) cell line (AT5BIVA) from complementation group D previously resulted in the isolation of a cell line (1B3) with partially restored resistance to ionizing radiation. We rescued the integrated cosmid sequences within 1B3 and obtained two cosmid clones that contained overlapping DNA from chromosomal region 11q23, previously shown to be the region containing the AT gene(s) from three complementation groups. Isolation of an apparently full-length 3.0-kb cDNA from a HeLa cell library demonstrated a previously unidentified gene (ATDC) within these cosmid clones. The transfected copy of the ATDC gene in 1B3 is truncated at the 3' end but is a complete transcription unit, because of the presence of SV40 termination sequences within the adjacent cosmid DNA. After further screening of cosmid clones from a chromosome 11 library, we identified contiguous DNA that contained the missing portion of the gene. Southern blot analysis indicated that the ATDC gene is present in a single copy in the human genome; however, RNA blot analysis revealed mRNA of several sizes (1.8, 2.6, 3.0, 4.7, and 5.7 kb) that varied among different cell lines. Because no large rearrangements were detected in AT5BIVA cells by Southern or RNA blot analysis, any alteration in the ATDC gene in this cell line would involve a point mutation or a small rearrangement. Transfection of the AT5BIVA cell line with one of the cosmids partially restored radioresistance. Analysis of 100 X-radiation hybrid cell lines containing various fragments from the chromosomal region 11q23 showed that the ATDC gene is closely linked to THY1. The ATDC gene therefore lies outside the linkage region predicted to contain the AT gene(s) for complementation groups A and C, indicating a separate locus for the AT complementation group D gene. PMID- 1609805 TI - Rapid detection of chromosome aneuploidies in uncultured amniocytes by using fluorescence in situ hybridization (FISH). AB - Herein we report the results of the first major prospective study directly comparing aneuploidy detection by fluorescence in situ hybridization of interphase nuclei with the results obtained by cytogenetic analysis. We constructed probes derived from specific subregions of human chromosomes 21, 18, 13, X, and Y that give a single copy-like signal when used in conjunction with suppression hybridization. A total of 526 independent amniotic fluid samples were analyzed in a blind fashion. All five probes were analyzed on 117 samples, while subsets of these five probes were used on the remaining samples (because of insufficient sample size), for a total of over 900 autosomal hybridization reactions and over 400 sex chromosome hybridization reactions. In this blind series, 21 of 21 abnormal samples were correctly identified. The remaining samples were correctly classified as disomic for these five chromosomes. The combination of chromosome-specific probe sets composed primarily of cosmid contigs and optimized hybridization/detection allowed accurate chromosome enumeration in uncultured human amniotic fluid cells, consistent with the results obtained by traditional cytogenetic analysis. PMID- 1609806 TI - A 1.6-Mb contig of yeast artificial chromosomes around the human factor VIII gene reveals three regions homologous to probes for the DXS115 locus and two for the DXYS64 locus. AB - Two yeast artificial chromosome (YAC) libraries were screened for probes in Xq28, around the gene for coagulation factor VIII (F8). A set of 30 YACs were recovered and assembled into a contig spanning at least 1.6 Mb from the DXYS64 locus to the glucose 6-phosphate dehydrogenase gene (G6PD). Overlaps among the YACs were determined by several fingerprinting techniques and by additional probes generated from YAC inserts by using Alu-vector or ligation-mediated PCR. Analysis of more than 30 probes and sequence-tagged sites (STSs) made from the region revealed the presence of several homologous genomic segments. For example, a probe for the DXYS64 locus, which maps less than 500 kb 5' of F8, detects a similar but not identical locus between F8 and G6PD. Also, a probe for the DXS115 locus detects at least three identical copies in this region, one in intron 22 of F8 and at least two more, which are upstream of the 5' end of the gene. Comparisons of genomic and YAC DNA suggest that the multiple loci are not created artifactually during cloning but reflect the structure of uncloned human DNA. On the basis of these data, the most likely order for the loci analyzed is tel DXYS61-DXYS64-(DXS115-3-DXS115-2)-5'F8-(D XS115-1)-3'F8-G6PD. PMID- 1609807 TI - Anticipation legitimized: unstable DNA to the rescue. PMID- 1609809 TI - On farm injuries and safety. PMID- 1609808 TI - Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. AB - A generalized deficiency of the mitochondrial matrix enzyme ornithine aminotransferase (OAT) is the inborn error in gyrate atrophy (GA), an autosomal recessive degenerative disease of the retina and choroid of the eye. Mutations in the OAT gene show a high degree of molecular heterogeneity in GA, reflecting the genetic heterogeneity in this disease. Using the combined techniques of PCR, denaturing gradient gel electrophoresis, and direct sequencing, we have identified three nonsense-codon mutations and one nonsense codon-generating mutation of the OAT gene in GA pedigrees. Three of them are single-base substitutions, and one is a 2-bp deletion resulting in a reading frameshift. A nonsense codon created at position 79 (TGA) by a frameshift and nonsense mutations at codons 209 (TAT----TAA) and 299 (TAC----TAG) result in abnormally low levels of OAT mRNA in the patient's skin fibroblasts. A nonsense mutation at codon 426 (CGA----TGA) in the last exon, however, has little effect on the mRNA level. Thus, the mRNA level can be reduced by nonsense-codon mutations, but the position of the mutation may be important, with earlier premature-translation termination having a greater effect than a later mutation. PMID- 1609810 TI - Non-fatal farm injuries on 117 eastern Ontario beef and dairy farms: a one-year study. AB - A one-year prospective survey was conducted to study the incidence of and potential risk factors for farm-related injuries in Eastern Ontario. One hundred and seventeen dairy and beef farms were surveyed using a personal interview. Information was collected on demographic characteristics of the farm owners, workers, and families; characteristics of the farm operations; and information on behaviors potentially affecting injury risk. Monthly telephone contact was then maintained with the farms for one year in order to document all farm-related injuries. Overall and specific injury rates were calculated. Treatment patterns for these injuries were described. The statistical significance of several potential risk factors for injury was evaluated; assessment of relative risk estimates (RR) and adjustment for confounding factors was done using logistic regression analysis. The overall farm injury rate was 7.0 persons injured per 100 person-years (95% C.I.: 4.9,9.1, n = 547). Common patterns of injury by ICD-9-E Code included accidents caused by farm machinery (E919.0), accidental falls (E880 8), and injuries caused by animals (E906). Variables found in multivariate logistic models to be predictive of injury occurrence were living on a beef farm (RR = 2.5; p = 0.01); increased farm work experience (trend: p less than 0.01); full-time exposure to farm work (RR = 2.5; p = 0.04); and, in farm owners, the use of prescriptions medications (RR = 2.7; p = 0.07). Forty-six percent of the farm-related injuries were treated in a hospital-based emergency department (ER). Efforts to monitor the incidence of farm injuries using an ER-based information system have the potential to significantly under-estimate the scope of the regional farm injury problem in Eastern Ontario. PMID- 1609811 TI - The dangers of dairy farming: the injury experience of 600 workers followed for two years. AB - In order to better understand the work-related injuries sustained on central New York dairy farms, we undertook a two-year population-based study of 600 farmers and farm workers on 201 dairy farms. During the observation period, 1984-1986, 151 persons had 200 injuries, giving an injury rate of 16.6%/year (166 injuries/1,000 workers/year). Men were injured more often than women (p less than or equal to 0.01). Injured workers were older (p less than or equal to 0.01), worked more hours (p less than or equal to 0.001), and had heavier workloads than noninjured workers (p less than or equal to 0.001). The growing and harvest seasons had the most injuries; winter the fewest. More than 2/3 of the injuries occurred in the afternoon. Owners/operators, often the most experienced, knowledgeable people on the farms, were most often hurt. Those working more than 60 hours/week, with greater than 30 acres under tillage/worker, had a relative risk of 2.76 compared with all other workers. The attributable risk for this group was 51%. There were two fatalities, both involved owner/operators. Our findings suggest that previous studies may have underestimated the risks faced by farmers. Dairy farming in central New York is very dangerous work. Those who own and operate these dairy farms are most often hurt and killed. Analysis of events on individual farms will be reported separately. PMID- 1609812 TI - A cohort study on cancer incidence among Danish gardeners. AB - This study was performed to examine the cancer risk of Danish gardeners having been highly exposed to pesticides. We have followed a cohort of 4,015 employed gardeners (859 females and 3,156 males) from May 1975 until the end of 1984 with regard to cancer incidence. The observed incidence was compared with expected numbers calculated from national incidence rates. For all cancer sites combined, the standardized morbidity ratio (SMbR) was 104. Among male gardeners a significantly increased incidence was seen for soft tissue sarcoma (SMbR = 526, 95% confidence interval (CI): 109-1,538), an chronic lymphatic leukemia (SMbR = 275, 95% CI: 101-599). The incidence of non-Hodgkin's lymphoma was twice that which was expected (SMbR = 200, 95% CI: 86-393). We suggest that some of the pesticides to which the gardeners have been exposed are capable of initiating or promoting the development of malignant neoplasms in tissues of mesenchymal origin. PMID- 1609813 TI - Clinical relevance of urinary delta-aminolevulinic acid/logarithm of creatinine ratio in screening for occupational lead exposure. AB - Using receiver operating characteristics (ROC) analysis, the clinical relevance of urinary delta-aminolevulinic acid concentration adjusted to the logarithm of creatinine concentration (ALA/log.Cn) proved to be better than that of uncorrected ALA or ALA/Cn ratio for the detection of blood lead levels (Pb-B) exceeding 2.5, 3.0, or 3.5 mumol/l in 483 men occupationally exposed to lead. Ala/log.Cn yielded validities of 1.63, 1.75, and 1.79 at Pb-B levels 2.5, 3.0, and 3.5 mumol/l, respectively. The same values for ALA/Cn were 1.59, 1.70, 1.78 and for ALA 1.52, 1.65, 1.72, respectively. The simple adjustment to log. Cn makes urinary ALA determination more efficient in biological monitoring of the effect of occupational lead exposure. PMID- 1609814 TI - Environmental household exposures to asbestos and occurrence of pleural mesothelioma. AB - We reviewed the certificates of 39,650 deaths which occurred in the period 1975 1988 in Leghorn and of 45,900 in La Spezia (Italy) in the period 1958-1988. In total 262 cases have been recorded as pleural mesothelioma. The main occupational exposures occurred in the shipbuilding industry. Regarding non-occupational exposures to asbestos, 13 cases of mesothelioma were found in women who had washed the work clothes of their relatives at home; we also found other domestic uses of asbestos which were rarely or never discussed previously in the literature: six cases might be explained by the installation of fireproof or non conductive materials in the domestic environment. These exposures probably are more frequent than realized until now. PMID- 1609815 TI - Patterns of asbestosis in New Jersey. AB - Hospital discharge data from New Jersey were used to identify cases of asbestosis for the 8 years 1979-1986. Multiple admissions were deleted so that each individual was counted once at the time of his/her first hospitalization with an asbestosis diagnosis. White males had the highest age-adjusted average annual discharge rate of 19.3 cases/100,000 population, followed by black males (12.3 cases/100,000) and white females (1.2 cases/100,000). The discharge rate was positively associated with age in each race/sex category. The relationship between rates for black males and white males depended on age: under 65 years, the rates were almost equal, and at 65 years and older, the white rates were nearly twice the black rates. There were two areas of the state where the rates were highest: the north-central and southwest regions. These two areas represent manufacturing and shipbuilding applications of asbestos, respectively. During the years 1979-1986, the annual percentage increase in asbestosis rates was 20% for white males, 17% for black males, and 8% for white females. Continued surveillance will reveal when the rates for asbestosis stop increasing. PMID- 1609816 TI - Occupation, smoking, and the risk of high-grade invasive bladder cancer in Missouri. AB - Numerous epidemiological studies have established that occupational exposures and smoking are the two major known risk factors for the development of bladder cancer. Using data from the Missouri Cancer Registry, we investigated the hypothesis that individuals with occupationally-related bladder cancer are more likely to have a more invasive form of the disease. Data were analyzed for 2,893 white males diagnosed with primary bladder cancer in Missouri between 1984 and 1988. Of the 1,415 cases whose occupational status was recorded, 236 (17%) were employed in high-risk occupations. Cases with high-grade disease were more likely to have been employed in a high-risk occupation, after adjustment for age and smoking (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.1 2.6). High-risk workers under 60 years of age were most at risk for developing high-grade bladder tumors (AOR = 2.3, 95% CI = 1.0-5.3). There was no overall association between high-risk occupation and late-stage disease (AOR = 1.1, 95% CI = 0.7-1.5), but it was present in the men younger than 60 years of age (AOR = 2.0, 95% CI = 1.0-3.8). No association was found between tobacco use and grade (AOR = 1.1, 95% CI = 0.8-1.5), but cases with late-stage disease were more likely to be smokers (AOR = 1.5, 95% CI = 1.1-1.9). When occupations were examined individually, motor vehicle operators, truck drivers, vehicle mechanics, other mechanics, and janitors were among those most likely to be diagnosed with high grade or late-stage tumors. Although further studies are necessary to confirm these results, they suggest that surveillance and targeted screening of workers in high-risk occupations may result in a greater yield of early invasive cancers and possibly decrease the mortality associated with this disease. PMID- 1609817 TI - Exposure-response relationships for coal mine dust and obstructive lung disease following enactment of the Federal Coal Mine Health and Safety Act of 1969. AB - Underground U.S. coal miners were studied cross-sectionally for the association of respirable coal mine dust exposure with pulmonary function and symptoms of airways obstruction. The study group included 1,185 miners participating in Round 4 of the National Study of Coal Workers' Pneumoconiosis who had started mining in or after 1970 when comprehensive exposure regulations first came into effect. Quantitative estimates of cumulative exposure, derived using respirable dust measurements taken by the Mine Safety and Health Administration over the entire study period, were used in linear and logistic regression models on indicators of pulmonary function and chest symptoms while controlling for smoking status, pack years, and other potential confounders. Statistically significant associations between log cumulative exposure and decrements in FVC, FEV1, and FEV1/FVC were observed. In logistic models, statistically significant associations of cumulative exposure with increasing prevalence of FEV1 and FEV1/FVC less than 80% predicted and symptoms including chronic phlegm, chronic bronchitis, breathlessness, wheeze, and wheeze with shortness of breath were found. It is concluded that exposures to respirable coal mine dust present in U.S. mines since 1970 continue to affect respiratory health in underground miners. PMID- 1609818 TI - Wittenoom, Western Australia: a modern industrial disaster. PMID- 1609819 TI - Perspectives on risk assessment impact of recent reports on benzene. AB - Very sensitive methods that can detect the benzene metabolite muconic acid (MA) in the urine of virtually all members of the general population have recently become available and have been used in a few occupational studies as a marker of benzene exposure. Preliminary findings from these studies suggest that urinary MA may be a reliable marker of occupational exposure to greater than 5 ppm benzene. It was also consistently observed that a certain proportion of the general population have urinary MA levels compatible with those seen in persons occupationally exposed to greater than 1 ppm benzene. It is unlikely that these elevated levels can be explained solely as being artifactual. The frequency with which they occur for a given individual, and the duration with which they are maintained, are not known. Information on these two factors is needed in order to adequately assess whether or not these levels present a significant risk for a segment of the general population. PMID- 1609820 TI - OSHA and standard-setting. PMID- 1609821 TI - Anthropometric studies in five children and their mother with a severe form multiple epiphyseal dysplasia. AB - We report on a form of multiple epiphyseal dysplasia with striking acromelic shortness in a woman and five of her ten children. The somatometric and metacarpo phalangeal pattern profile of the affected individual showed short limb dwarfism and shortness of all the tubular bones of the hand. Epiphyseal irregularities and shortness of the 4th metatarsal bones were outstanding. The disorder showed a dominant and probably autosomal pattern of inheritance with variability of expression. The measurement of metacarpo-phalangeal profiles allowed an objective and quantitative assessment of brachydactyly. In the family reported here, there was a clear discrepancy between the severity of shortness of hands and feet and the severity of shortness of stature. This family also illustrates the effects of a single gene in a large kindred, therefore describing the range and variability of a phenotype not otherwise available. PMID- 1609822 TI - Inbreeding effect on morbidity: IV. Further data in Brazilian populations. AB - The analysis of the data on 5677 children of 1063 couples from a fourth sample of consanguineous and nonconsanguineous marriages among whites and nonwhites living in the State of Minas Gerais, Brazil led to the following estimates: B (number of abnormal equivalents per gamete) around 0.5; A (morbidity in the non-inbred subsamples) 2-3 percent; B/A 13, 15, and 27 (this suggests that the morbidity disclosed by inbreeding may predominantly represent a mutational load); RR (relative risk) about 2 (this means that among the children of consanguineous marriages there is about double the frequency of abnormalities than in those with nonconsanguineous marriages); AR (attributable risk) for the whole sample about 7% (5% for nonwhites and 15% for whites). These last values show the amount that the frequency of abnormalities would decrease in the population if the risk factor (consanguineous marriages) would be eliminated. AR is higher in whites because the frequency of the risk factor is higher among whites. PMID- 1609823 TI - Nonrandom association of atrioventricular canal and del (8p) syndrome. AB - We describe a patient with partial deletion of the short arm of chromosome 8 with an atrioventricular canal. This type of congenital heart defect was found in 4 of the 7 previously reported del (8p) children with a congenital heart defect in which the cardiac assessment was complete. The prevalence of an atrioventricular canal in this aneuploidy is high and suggests a nonrandom association of the 2 anomalies. PMID- 1609824 TI - Fat distribution in overweight patients with Ullrich-Turner syndrome. AB - Overweight patients with Ullrich-Turner syndrome (UTS) and control children with similar weight/height and indices of overweight were studied to clarify the unique fat distribution in the syndrome. Triceps and ulnar skin-fold thickness (SFT) in UTS patients was significantly less than that of obese children without the syndrome. The means of SFT at the subscapular and paraumbilical regions were also less in the patients than control girls, though significance was not documented. Thus, increased body weight in UTS children seems mainly to be due to excess of adipose tissue, not in the limbs but on the trunk, and/or due to the increment of lean body mass. PMID- 1609825 TI - Molecular nosology of heritable disorders of connective tissue. PMID- 1609826 TI - Short stature, mental retardation, eye anomalies, and cleft lip/palate. AB - The syndrome: We describe 3 Brazilian brothers presenting a cluster of signs strongly suggesting a "new" MCA/MR syndrome. The main clinical signs include short stature, microbrachycephaly, mental retardation, palpebral ptosis, coloboma of iris and retina, nystagmus, strabismus, and cleft lip/palate. This is either an autosomal or X-linked recessive trait. PMID- 1609827 TI - Amplification of ten deletion-rich exons of the dystrophin gene by polymerase chain reaction shows deletions in 36 of 90 Japanese families with Duchenne muscular dystrophy. AB - We analyzed DNA samples taken from 95 Duchenne muscular dystrophy (DMD) patients belonging to 90 different families in Japan using the polymerase chain reaction. Ten different regions at the 5' end or in the central region of the dystrophin cDNA gene that were previously shown to be prone to deletion were selected for amplification and analysis. Patients in 36 of the 90 families (40%) had deletions in at least one of these segments of the gene. Identical deletions were detected in the dystrophin gene of patients from the same family. The deletions were heterogeneous in size and location. One patient had deletions in 7 of the 10 amplified regions, while 19 patients from 18 families had a deletion in only one of the regions studied. Deletions at the 5' end were generally larger and more heterogeneous than those in the central region of the gene. One third of deletions had their proximal end breakpoints between exons 44 and 45. This region seems to be particularly vulnerable to gene breakage in DMD patients. PMID- 1609828 TI - Dextrocardia, microphthalmia, cleft palate, choreoathetosis, and mental retardation in an infant born to consanguineous parents. AB - We report on an infant (born to consanguineous parents) with an unusual face, microphthalmia, cleft palate, dextrocardia, choreoathetosis, and mental retardation. This child has many traits in common with an infant recently described by Aughton [1990] as a probable new syndrome. PMID- 1609829 TI - Hemifacial microsomia: developmental consequence of perturbation of the auriculofacial cartilage model? AB - The cause of hemifacial microsomia (HFM) is currently the subject of much investigation. Despite a large body of clinical and experimental data, little is certain other than the heterogeneity of this malformation complex. Here we suggest that some of the cases previously designated as being multifactorial in origin may be interpreted instead as resulting from a single-gene mutation, by applying a stochastic single-gene model. A variety of models of the pathogenesis of HFM have been described, including the proposal that local embryonic haemorrhage is a causal mechanism. More recently, it has been suggested that an interference in chondrogenesis is primarily responsible for the HFM phenotype. In this paper direct experimental evidence, based on surgical interference of mandibular development in the chick embryo, is applied in favour of the latter concept. In particular, asymmetrical perturbation of Meckel's cartilage has been shown to result in asymmetry of the mandible, and it is proposed that, irrespective of cause, the skeletal pathogenesis of HFM primarily involves the auriculofacial cartilage model. PMID- 1609830 TI - Marden-Walker-like syndrome without psychomotor retardation: report of a Brazilian girl born to consanguineous parents. AB - We report on a Brazilian girl, born to consanguineous parents and presenting a multiple congenital anomaly (MCA) syndrome, mainly characterized by blepharophimosis, cleft palate, and arachnodactyly. The clinical aspects involving this patient suggest an apparently undescribed "new" autosomal recessive syndrome. PMID- 1609831 TI - Constrictive amniotic bands, amniotic adhesions, and limb-body wall complex: discrete disruption sequences with pathogenetic overlap. AB - In a fetopathologic evaluation of 18 cases with amniotic bands, we discerned 3 types of lesions: (1) constrictive tissue bands, (2) amniotic adhesions, and (3) more complex anomaly patterns, designated as limb-body wall complex (LBWC). Constrictive bands are caused by primary amnion rupture with subsequent entanglement of fetal parts (mostly limbs) by shriveled amniotic strands. Adhesive bands are the result of a broad fusion between disrupted fetal parts (mostly cephalic) and an intact amniotic membrane. Most of the craniofacial defects (encephaloceles and/or facial clefts) occurring in these fetuses are not caused by constrictive amniotic bands, but are the result of a vascular disruption sequence with or without cephalo-amniotic adhesion. Our observations confirm the fact that amnion rupture is not a conditio sine qua non for the development of LBWC. However, LBWC is often complicated by rupture of the unsupported amnion with ensuing formation of constrictive bands. We think that the concept that considers the 3 lesions in question as a single pathogenetic entity is erroneous and will inevitably lead to a never-ending debate between followers of the 2 prevailing theories. In our view, the theories of Streeter and Torpin are not mutually exclusive but rather apply to different types of lesions. The recognition of constrictive amniotic bands, amniotic adhesions, and LBWC as discrete but often combined disruption sequences with important pathogenetic overlap may resolve many dilemmas in interpretation when a fetus exhibits classical constrictive bands beside more severe defects. PMID- 1609832 TI - Perspective of biochemical research in the neuronal ceroid-lipofuscinosis. AB - The search for biochemical abnormalities in the neuronal ceroid-lipofuscinoses (NCL) or Batten disease was initiated with the discovery of normal levels of gangliosides in juvenile amaurotic idiocy. The primary goal of most biochemical studies has been to discover the unique biochemical marker for carriers and at risk individual. Ceroid, the singular pathomorphologic trait of NCL, was isolated and shown to differ from a similar but normal product of aged cells, lipofuscin. In spite of the availability of stored product, the chemical analysis of ceroid has not elucidated the unique biochemical defect in the NCL, as has been the case for other lysosomal storage disorders. The NCL were thought to be a result of lipid peroxidation because ceroid is also found in disorders of impaired vitamin E metabolism or results from a diet deficient in the antioxidant, vitamin E. In addition, tissue analysis indicated losses of polyunsaturated fatty acids in affecteds and carriers, as well as the presence of a secondary product of lipid peroxidation, 4-hydroxynonenal, in affected and carrier NCL dogs. With the exception of a fluorescent compound isolated from retinal ceroid, studies aimed at discovering the disease-specific fluorophores of ceroid have been largely inconclusive. The discovery of elevated dolichols in urine and brain tissue of NCL patients led to another hypothesis, that the basic biochemical defect in NCL involved the metabolism of dolichols and retinoids. However, the more recent view is that dolichol metabolism is secondary to the unknown NCL lesion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609833 TI - Neurology of the neuronal ceroid-lipofuscinoses: late infantile and juvenile types. AB - My experience with more than 80 cases of the late infantile and juvenile forms of the neuronal ceroid-lipofuscinoses over the last 5 years has led to the following realizations. The 2 variants are neurologically distinct entities and probably are the result of different genetic defects. Treatment includes supportive measures and anticonvulsant medication. Therapy for behavioral and psychiatric disturbances in the juvenile type proves to be particularly challenging as neuroleptic medications tend to worsen parkinsonian like symptoms. Neuropathologic and neuroradiologic explanation of clinical symptomatology correlates best with neuronal loss and not neuronal storage. There is a paucity of neuropathologic documentation of these 2 types; additional reports are encouraged. PMID- 1609834 TI - Incidence of neuronal ceroid-lipofuscinoses in West Germany: variation of a method for studying autosomal recessive disorders. AB - The incidence of neuronal ceroid-lipofuscinoses (NCL) in West Germany was determined using a novel method which is applicable to other autosomal recessively inherited diseases. Questionnaires were sent to all pediatric departments (answer rate 189/276, 68%), schools for the blind (39/46, 85%), and neuropathological institutes (15/22, 68%). Diagnoses were accepted only when based on firm clinical and/or electron microscopic criteria; 207 such identified patients were sorted according to year of birth. Plotting the cumulative number of new cases per year against the year of birth resulted in a slightly S-shaped curve. Before the year 1962, the curve is relatively flat, probably due to inefficient case registration. Between 1968 and 1977, the slope of the curve is constant--a steep, nearly straight line. Thereafter the curve flattens out again, likely due to inefficient registration of young, still undiagnosed patients. We interpret the central segment of the curve, which is continuously straight over a period of 10 years and corresponds to 92 patients, as a period in which efficient registration of new cases occurred. The number of live births being 7,211,543 during the same period, the NCL incidence is calculated to be 1.28 per 100,000 live births (0.71 for juvenile NCL and 0.46 for late infantile NCL). PMID- 1609836 TI - Linkage map of the chromosomal region surrounding the infantile neuronal ceroid lipofuscinosis on 1p. AB - The neuronal ceroid lipofuscinoses (NCLs) of childhood are divided into 3 main types according to age-of-onset, clinical course, and neurophysiological and neuropathological findings: infantile, late infantile, and juvenile. All forms are inherited as an autosomal recessive trait, and their biochemical background is still unknown. The infantile type (INCL) with the earliest age-of-onset and the most severe clinical course, occurs in Finland with an incidence of 1:20,000, i.e., 116 patients have been found in our country up to now, whereas only about 50 cases have been reported from other parts of the world. Earlier we reported the linkage of INCL to the short arm of chromosome 1. Here we describe a more precise linkage map of this area. Our current map places the INCL mutation between D1S57 and D1S79; D1S7 has so far shown no recombination events between the marker and the disease (lod score 4.55 at theta = 0.00). Our material includes 64% of all living patients in Finland, and no linkage disequilibrium of haplotypes is seen, using the 2 physically close markers D1S57 and D1S79. This finding as well as our LINKMAP analyses suggest that the distance between the disease locus and the flanking markers is about 3-4 cm. PMID- 1609835 TI - Linkage analysis in juvenile neuronal ceroid lipofuscinosis. AB - Neuronal ceroid lipofuscinosis (NCL, Batten disease) is an autosomal recessive disease characterized by progressive mental retardation, cortical atrophy, seizures, and retinal degeneration. Several subtypes have been delineated on the basis of age-at-onset and histological characteristics; the most common is the juvenile (JNCL) form. Recently, the gene for JNCL was shown to reside on chromosome 16 through linkage studies to the haptoglobin locus and anonymous DNA markers using numerous European families. We have now examined 8 families from North America with JNCL for linkage to markers in 16q21-23. Results in 3 families tend to support linkage to chromosome 16;3 families remained uninformative, and 2 families produced negative lod scores in this region. A test of homogeneity was suggestive, but could not significantly reject the null hypothesis of homogeneity. We are continuing to collect families, particularly those with multiple living affecteds, and are identifying other probes in this region. Given close localization on chromosome 16 for JNCL, molecular strategies, including candidate gene strategies, are being explored. PMID- 1609837 TI - Evidence for lipase abnormality: high levels of free and triacylglycerol forms of unsaturated fatty acids in neuronal ceroid-lipofuscinosis tissue. AB - Total lipid obtained from normal and different forms of neuronal ceroid lipofuscinoses (NCL) tissues was analyzed by high performance thin layer chromatography (HPTLC). We observed a large (greater than 6-fold) increase in a lipid band corresponding to triolein for NCL dog pancreas and spleen and juvenile human NCL brain and infantile NCL spleen. The accumulation was less pronounced for the brain samples but apart from increased dolichol-monophosphate levels, other lipids appeared normal. Normal dog, goat, or human spleen contained virtually no triacylglycerol, and of the pathological controls, beta-mannosidosis goat spleen showed no triacylglycerol band at all. A sample of human spleen from a patient with lymphoma-associated splenomegaly displayed a strong triacylglycerol band, but gas chromatography-mass spectrometry (GC/MS) of the bands showed an equal increase in both saturated and unsaturated fatty acid containing triacylglycerols in the splenomegaly sample, in keeping with the notion of non-specific fat deposition in damaged tissue. In contrast, in all the NCL samples (spleen, pancreas, and brain) a prominent increase in the proportion of unsaturated fatty acids was observed in both free fatty acid and/or triacylglycerol bands following GC/MS. The NCL-English setter dog pancreas showed a major presence of oleic acid (18:1) (twofold increase) as compared to normal, while dog and infantile human NCL spleen samples and juvenile Batten brain (human) displayed a robust increase in linoleic acid (18:2) and sometimes in oleic acid and arachidonic acid (20:4) (for infantile human NCL spleen). For the infantile human NCL spleen sample an increase in linoleic acid in both free fatty acid (3.2-fold) and triacylglycerol (10-fold) was observed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609838 TI - Biochemical studies on the juvenile form of ceroid-lipofuscinosis. AB - Accumulation of oligosaccharyl diphosphodolichols (oligo-PP-Dol) in brains of patients with various forms of ceroid-lipofuscinoses (CL) is one of the most reproducible biochemical changes known so far. The objective of this study is to understand the biochemical basis of this observation. The biosynthesis of oligo PP-Dol was studied by the incorporation of labelled glucose from UDP [14C]glucose into oligo-PP-Dol in cultured skin fibroblasts, and showed no changes in the level of synthesis. The level of labelled glucose incorporated into glycoproteins was also unchanged, suggesting that there is no decrease in the oligosaccharide transfer to proteins in this disorder. Since the biosynthesis and utilization of oligo-PP-dol are unaffected, a defect in the catabolism may be the only possibility for the storage of this compound in CL. Since terminal mannose residues are present in the accumulating oligo-PP-Dol, mannosidase activities at pH 4.4 and 6.0 were determined in cultured skin fibroblasts. Both mannosidase activities were unchanged in skin fibroblasts of juvenile CL. Endo-beta-N acetylglucosaminidase-1 activities were determined in cultured skin fibroblasts using dansylated Man6GlcNAcGlcNAc-Asn as substrate. In three patients, a drastic reduction in the level of the pH 4.5 enzyme was shown, while the neutral pH enzyme activity was unaffected. A deficiency of the endo-beta-N acetylglucosaminidase-1 will not only explain the accumulation of oligo-PP-Dol but also the known storage of high-mannose glycoproteins. PMID- 1609839 TI - Stored dolichyl pyrophosphoryl oligosaccharides in Batten disease. AB - Each of the 3 childhood forms of Batten disease, juvenile (JB), late-infantile (LIB), and infantile (IB), have abnormally high brain concentrations of dolichyl pyrophosphoryl oligosaccharides (Dol-PP-OS). In this study, the carbohydrate portions of Dol-PP-OS were analysed: in JB and LIB, they range in size from Man2GlcNAc2 to Glc3Man9GlcNAc2, predominant components being Man5-7GlcNAc2 and Glc3Man7GlcNAc2. In IB, they range from Man6-9GlcNAc2, no glucose containing oligosaccharides being identified. In Batten disease, the main subcellular location of Dol-PP-OS is within storage material, where it represents up to 7% of the dry weight. [3H]-Mannose incorporation experiments with cultured fibroblasts show that synthesis of Dol-PP-OS in JB is normal. We infer that the glycosylation intermediate Glc3Man9GlcNAc2-PP-dolichol is synthesised normally within the endoplasmic reticulum in Batten disease, but that catabolic derivatives accumulate within the lysosomes. It is unclear whether this process is central to the pathogenesis of the disease, though in IB a defect in the release of mannose residues from Dol-PP-OS is a distinct possibility. PMID- 1609840 TI - Evidence for processing of dolichol-linked oligosaccharides in patients with neuronal ceroid-lipofuscinosis. AB - In agreement with reports from other laboratories, we have shown that patients with the juvenile or late infantile forms of neuronal ceroid-lipofuscinosis (NCL) have greatly increased levels (5-fold to 20-fold) of dolichyl pyrophosphoryl oligosaccharides in their cerebral gray matter. Oligosaccharides containing 2 GlcNAc residues and 3 to 9 mannose residues were liberated by mild acid hydrolysis. The oligosaccharide profile given by brain tissue from 2 patients with infantile NCL was markedly different from that of late infantile and juvenile NCL brain, with Man9GlcNAc2 as the most abundant component and decreasing amounts of Man8- Man7- and Man6GlcNAc2. By contrast, Man5GlcNAc2 was the most abundant oligosaccharide present in all juvenile NCL brain samples analyzed. Both the susceptibility of the isolated Man5GlcNAc2 to endoglucosaminidase H digestion and permethylation analysis clearly indicated that it is not an intermediate in the biosynthesis of Glc3Man9GlcNAc2-PP-dolichol but has undergone catabolism, probably either in the endoplasmic reticulum or in the Golgi apparatus. Treatment of cultured skin fibroblasts for 7 days with N methyldeoxynojirimycin, a potent inhibitor of the endoplasmic reticulum processing enzymes glucosidase I and II, resulted in an accumulation of the same Man5GlcNAc2-PP-dolichol species that was elevated in juvenile NCL brain. The level in untreated fibroblasts was undetectable, suggesting that inhibition of processing glucosidases has interfered with the regulation and compartmentalization of lipid-linked oligosaccharides. PMID- 1609841 TI - Niemann-Pick type-C disease: deficient intracellular transport of exogenously derived cholesterol. AB - NPC disease is an autosomal recessive neurovisceral storage disorder. A pleiotropic array of secondary enzymatic and storage abnormalities has in the past obscured a cohesive understanding of the underlying metabolic basis of this disorder. Recent findings, reviewed in this report, demonstrate that NPC disease is a cholesterol lipidosis resulting from defective intracellular cholesterol transport. The sequence of cellular events characteristic of NPC is 1) deficient intracellular transport of exogenously derived cholesterol resulting in retarded induction of cellular cholesterol homeostatic regulation; 2) accumulation of cholesterol in lysosomes; and 3) secondary cellular effects. Retarded esterification of exogenous cholesterol and accumulation of unesterified cholesterol in lysosomes is tightly coupled to the primary defect and serves as the basis for biochemical diagnosis of NPC. PMID- 1609842 TI - English setter model and juvenile ceroid-lipofuscinosis in man. AB - The etiology of the juvenile type of the human ceroid-lipofuscinosis (JCL) is unknown, in spite of the fact that the first report of this disease was given more than 160 years ago. The necessity of good animal models for scientific progress in chronic metabolic diseases in humans is obvious. The inbred strain of English setter with ceroid-lipofuscinosis (CCL) seems to be a perfect model for human JCL. Dogs with CCL and organs for research purposes are available from Dr. Koppang's experimental kennel in Norway. PMID- 1609843 TI - Retina in various animal models of neuronal ceroid-lipofuscinosis. AB - The childhood forms of human neuronal ceroid-lipofuscinosis (NCL) are invariably associated with a severe progressive retinopathy which commences at the photoreceptor level morphologically and proceeds to a final loss of neuronal cells accompanied by severe gliosis. In respective spontaneous animal conditions of NCL, in English setters, Dalmatian dogs, and New Zealand sheep, retinal involvement is not commensurate although the retina does not seem to be completely unaffected. In canine NCL, there might be functional and electro physiological impairment of retinal cells, but retinal atrophy is not obvious. In ovine NCL, the retina, apart from accumulating NCL-specific lipopigments within neuronal perikarya, also shows loss of photoreceptors. Conversely, retinal pigment epithelial cells (RPE) in canine and ovine NCL contain peculiar lamellar inclusions, not seen in unaffected animals, possibly an indication of a disturbed phagocytic process of photoreceptor outer segments. Similar such lamellar inclusions have not been observed in RPE cells in human childhood NCL. PMID- 1609844 TI - Tibetan terrier model of canine ceroid lipofuscinosis. AB - Over a 10-year period, we have studied the Tibetan terrier's visual electrophysiology, light and electron microscopic (EM) retinal characteristics of a slowly evolving inherited ceroid lipofuscinosis (CL). The retinal degeneration with CL inclusions (rdi) in the inner nuclear layer (bipolar cells) and nerve fiber layer (ganglion cells) has been called "rdi" to differentiate the visual abnormality from typical early retinal degeneration (erd) reported also in the Tibetan terrier. The unique "rdi" electroretinogram (ERG) gives a predominant P III wave at age 7 weeks but becomes more characteristically depressed in all phases over several years. Nyctalopia is the only functional abnormality for the first 5 to 6 year of life. Signs are remarkably few considering the pathology. Microscopic studies of the retina show accumulations, increasing with age, of autofluorescent dense inclusion particles which stain intensely by Luxol fast blue, PAS, and acid-fast procedures. Ultrastructural studies of the retina show the dense particles to be lamellar membranes repeating every 2 to 4 nm, consistent with ceroid lipofuscin. The inner retinal layers were always the target layer to be affected first and most severely. The ganglion cells were most frequently involved. The photoreceptors eventually degenerated but relatively few particles were found in this layer. The cytosomes in the cerebral cortex and brainstem neurons resemble lipofuscin, containing granular, lamellar, and globular components. Different pigment bodies were present in the cerebellar Purkinje cells. Neuronal loss which was moderate in the cerebellum and mild in the cerebrum was accompanied by astrogliosis and a striking presence of macrophages.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609845 TI - Amelioration of clinical disease following bone marrow transplantation in fucosidase-deficient dogs. AB - Canine fucosidosis was studied as an animal model for the treatment of neurovisceral lysosomal storage disease. Following successful bone marrow engraftment, dogs with fucosidosis had increased levels of alpha-L-fucosidase enzyme activity in leukocytes, plasma, and neural and visceral tissues. This widespread increase in enzyme activity was accompanied by a rapid improvement in the peripheral nerve and visceral lesions of fucosidosis and a more gradual improvement in the central nervous system pathology. Long-term engraftment from an early age reduced the severity and slowed the progression of clinical neurological disease. Transplantation after the onset of clinical signs was not effective. These findings suggest that the neurological damage caused by some inherited metabolic disorders, such as fucosidosis, may be preventable but emphasise the need for early diagnosis and treatment. PMID- 1609846 TI - Monozygotic twinning and Wiedemann-Beckwith syndrome. AB - Monozygotic (MZ) twinning occurs with relatively high frequency in Wiedemann Beckwith syndrome (WBS). Ten sets of MZ twins with WBS have been reported. Nine of these have been female and in each case the twins were discordant for the WBS phenotype. The tenth set was male. They were concordant for WBS and both had a duplication of chromosome 15 which they shared in common with their phenotypically normal mother. The WBS gene has been assigned to the locus 11p15 and there appear to be several different genetic mechanisms involving this locus which all give rise to WBS. An imprinting effect for the WBS gene has been proposed because of the transmission of the gene preferentially through the maternal line in some large pedigrees. We describe two further sets of female MZ twins with WBS. One pair is concordant and one discordant for the condition. The possible genetic mechanisms involved in the expression of WBS are discussed, with particular reference to twinning, genomic imprinting and X-inactivation which is thought to be associated with the occurrence of MZ twinning in females. PMID- 1609847 TI - Recurrent Wiedemann-Beckwith syndrome with inversion of chromosome (11)(p11.2p15.5). AB - A baby with Wiedemann-Beckwith syndrome (WBS) and her phenotypically normal mother carried the same paracentric inversion, inv(11)(p11.2 15.5), in the short arm of chromosome 11. A fetus, sib of the affected baby, had the same inversion and ultrasound scan showed exomphalos. The maternal grandmother is clinically and cytogenetically normal. The pattern of affection in this family is consistent with the suggestion that WBS can be caused by lack of a maternally imprinted gene at 11p15.5, and that in this family the inversion disrupts that gene. PMID- 1609848 TI - Histopathologic and ultrastructural changes in the temporal bones of HIV-infected human adults. AB - Acquired immunodeficiency syndrome (AIDS) is a devastating disease that is affecting the human population in epidemic numbers. Patients with AIDS are known to have a significant incidence of otologic disease, including hearing loss, vertigo, tinnitus, otalgia, and infection with unusual pathogens. There has been no previous work on the histopathology of this disease. Ten temporal bones from five patients who were seropositive for the human immunodeficiency virus (HIV), the causative retrovirus of AIDS, were obtained. Seven specimens were analyzed using light microscopic techniques. Electron microscopy was performed on selected areas of pathology. A myriad of pathologic findings was seen, including severe petrositis with marrow replacement, mastoiditis, otitis media, ossicular destruction, precipitations in the perilymphatic and endolymphatic spaces of the vestibule and of the semicircular canals, and subepithelial elevation of the neurosensory epithelium of the saccule and utricle. The organ of Corti was relatively free of pathologic change. Many of the otologic symptoms encountered in these patients can be explained by the findings in this study. Further investigation using light and electron microscopy, and immunohistochemical techniques, is urged. PMID- 1609849 TI - Longitudinal evaluation of communication skills of children with single- or multichannel cochlear implants. AB - Performance on speech perception, speech production, and language tests was measured over time in children who used the 3M/House or the Nucleus cochlear implant. The speech perception and production results demonstrated higher performance levels and faster rates of learning for the multichannel than for the single-channel users. The performance of the children with the single-channel implant on the speech perception and production measures reached a plateau by 1.5 years post implant, whereas the children using the multichannel device continued to show improvement after 2 or more years of implant use. Changes in language were limited over time with no obvious difference in performance as a function of type of implant. PMID- 1609850 TI - Facial nerve management in temporal bone hemangiomas. AB - Eight patients with intratemporal hemangiomas involving the facial nerve are reported to present their symptoms, pathology, surgical management, and results. These unusual tumors have a predilection to involve the facial nerve, usually at the geniculate ganglion, internal auditory canal, or middle ear. Patients presented with facial palsy that was sudden, gradual in onset, recurrent, or associated with hemifacial spasm. Symptoms often progressed for years before the diagnosis was made. In two cases the tumor caused bony remodeling with an expansile honeycombed appearance, but no neoplastic production of bone. The facial nerve was comprised either by tumor compression or nerve invasion, as seen in two of our patients. Complete removal of the tumor and rehabilitation of the facial nerve function was attained in each case. Because of the destructive nature of these benign tumors, intratemporal facial nerve grafting was required in five of the eight cases. Results of facial nerve repair were good except in cases of long-standing facial dysfunction. PMID- 1609851 TI - Recurrence rates of acoustic neuroma in hearing preservation surgery. AB - Several authors have detailed the microscopic appearance of the acoustic neuroma/cochlear nerve interface. Others have highlighted the anatomic relationships existent between the lateral end of the internal auditory canal (fundus) and the otic capsule, as viewed from the posterior fossa. Based on these findings, several have suggested that hearing preservation attempts are likely associated with tumor persistence. They therefore question the feasibility of hearing preservation surgery. In this study, computerized tomography or magnetic resonance imaging was carried out on 28 patients having previously undergone excision of an acoustic neuroma with intraoperative sparing of the cochlear and facial nerves. Scans were done at least 5 years following surgery. Results of this study and a discussion of the literature follow. PMID- 1609852 TI - Three-dimensional CT scan reconstruction for the assessment of congenital aural atresia. AB - Major advances in medical computer graphics workstations have provided the capability to produce high quality three-dimensional image reconstructions from conventional thin-section computerized tomography (CT) scans with the ability to observe the imaged structure from any angle, with views and dimensions that are comparable to actual dissections. We have applied this technique to the temporal bone to assess congenital aural atresia in surgical planning for hearing reconstruction in six patients. The digital information produced by thin-section CT scanning allowed for the re-creation of multiplanar reformatted, shaded surface, and volumetric images. With this technique the surface landmarks of the temporal bone were readily visualized, the configuration of the atretic plate and middle ear in relation to the tegmen and glenoid fossa could be precisely assessed and the structure of the ossicular mass was easily analyzed. Most significantly, the facial nerve could be accurately and easily envisioned in its entire intratemporal course. Three-dimensional imaging is a highly desirable means for observing CT scan data to facilitate the surgical planning for correction of congenital aural atresia. PMID- 1609853 TI - Temporal bone histopathology of a patient with a nucleus 22-channel cochlear implant. AB - The temporal bone histopathology of a patient with profound sensorineural hearing loss attributable to cochlear otosclerosis is presented. The patient had a Nucleus 22-channel cochlear prosthesis implanted in the right ear prior to his demise. Unintentional scala media insertion of the electrode array resulted from labyrinthitis ossificans obliteration of the scala tympani. Inadvertent facial nerve stimulation necessitated program exclusion of electrodes 11 to 16 located in proximity to the labyrinthine and geniculate segments of the facial nerve. The patient received significant benefit from use of the device. The histopathologic findings are correlated with psychophysical and speech perception results. PMID- 1609854 TI - Utility of headshake versus whole-body VOR evaluation during routine electronystagmography. AB - Evaluation of the vestibulo-ocular reflex (VOR) by caloric testing yields important localizing information, but does not examine the entire frequency spectrum of vestibular function. With the addition of head rotation at 0.5 Hz (50 deg/s) and a velocity sensor to measure head movement, additional unique information regarding higher frequency VOR function can be readily obtained using standard electro-oculography (EOG). Over the past 4 years, active head-on-body and passive whole-body rotation testing with four-channel strip-chart recording and hand analysis have been routinely performed on every patient referred for caloric testing. In 95 percent of cases with normal symmetric caloric responses, headshake VOR gain with either stimulus was normal (greater than 0.51). Similarly, more than 95 percent of patients with unilateral deficits on caloric testing yielded normal rotational VOR gains. In contrast, roughly one third of patients with bilaterally reduced caloric responses demonstrated both abnormally low active headshake and passive whole-body rotational gain (less than 0.5). It appears, therefore, that both active head-on-body and passive whole-body rotation VOR testing at 0.5 Hz are possible using standard recording techniques, and yield valuable added information in cases with reduced bilateral caloric responses. PMID- 1609855 TI - Surgical management of perilymphatic fistulas: a Portland experience. AB - A comprehensive review of our series of surgical perilymphatic fistula (PLF) repairs, as well as a review of published results from other otologists, suggested an unacceptably high rate of postoperative PLF recurrence. Some recurrences were related to specific events (i.e., coughing, strenuous activity, Valsalva-type maneuvers). However many cases had no apparent cause. Rather, the patients' symptoms recurred spontaneously, and at reoperation the graft was seen to have not "taken," suggesting graft failure rather than "patient failure." After a critical evaluation of current PLF surgical procedures and state-of-the art concepts of wound healing, we developed a new surgical technique for PLF closure. Combining the use of laser graft-site preparation, an autologous fibrin glue "buttress," and a program of postoperative activity restriction, the new procedure allowed us to achieve statistically significant improvements in graft retention and surgical outcome, with recurrences dropping from 27 percent to 8 percent. In addition, complete resolution or significant symptomatic improvement occurred in 89 percent of patients with vertigo and/or dizziness and in 84 percent with disequilibrium. We conclude that this new surgical technique is an important addition to the otologic surgeon's arsenal for PLF management. PMID- 1609856 TI - Positional audiometry in the diagnosis of perilymphatic fistula. AB - Fifty-eight cases with a presumptive clinical diagnosis of perilymphatic fistula (PLF) are described with the results of a positional audiometric test designed to detect the presence of air in the cochlea. All patients underwent tympanotomy and observations of the middle ear are recorded together with the results of treatment. A definite leak was found in 33 cases and none in 25, but grafting of the round and oval window was performed in all but 10 cases. Pure-tone audiometry was performed before and after a 30-minute period of positioning the patient horizontally with the affected ear uppermost. A change in audiometric thresholds was noted in the group where a presumptive diagnosis of PLF was made, including some of those not found to have leaks at operation. However these changes were not observed in the positional tests of a group of 22 patients with hearing losses attributable to other causes. Also, an abnormal air-bone gap was noted in the PLF group compared with the other group. Although the original two-frequency criteria of earlier studies applied to the positional test did not predict the operative findings (leak or no leak), new data on frequency specific changes are presented. It is possible that fistulas at the oval window may be associated with positional threshold change at 500 Hz, and those at the round window with changes at 8 kHz. PMID- 1609857 TI - Perilymphatic fistula induced by barotrauma. AB - The association between diving, barotrauma, and the production of perilymphatic fistula has been known for almost 20 years. Forty-eight cases of round and oval window fistulas following diving have been reviewed and essentially corroborate previous findings. Any patient with a history of diving and subsequent sensorineural hearing loss within 72 hours should be suspected of having a round or oval window perilymphatic fistula and surgical exploration and closure of the fistula should be undertaken. Patients who have a loss of hearing, vertigo, nausea, or vomiting following a decompression dive should be re-compressed and if symptoms do not clear, exploration should be performed. Surgical treatment should be executed as soon as possible after the diagnosis is suspected for the best possible results. PMID- 1609858 TI - Prevention of recurrent cholesteatoma: use of hydroxyapatite plates and composite grafts. AB - Recurrent cholesteatoma after closed techniques occurs in four patterns: (1) through an attic defect, (2) via erosions in the canal wall, (3) as a pars tensa invagination, and (4) as a borderline invagination between an attic defect repair and a normal pars tensa. Semicircular porous hydroxyapatite ceramic plates 7, 10, and 14 mm in diameter, and 1 mm thick are used as underlays to repair attic defects, supplemented by bone dust pate and fine tragal cartilage-perichondrium composite grafts. Pate and either the tragal composites or fine tragal cartilage shavings are used to minimize the risk of wall erosion pockets. Borderline invaginations and pars tensa recollapse are prevented with the fine tragal composites. The extent of pars tensa reinforcement is determined by the extent of disease. Care to anticipate and prevent each of the four patterns has produced a comprehensive reduction of recurrent cholesteatoma to acceptable levels (under 10%). Residual disease, found in 19 percent of second stage cases, has required open conversion in only 3 percent of cases. The above techniques therefore provide optimal results and are recommended as routine closed cavity techniques. PMID- 1609859 TI - Professional attitudes regarding counseling of hearing-impaired adults. AB - To determine contemporary thinking regarding initial counseling of hearing impaired adults 500 questionnaires were mailed to otologists and otolaryngologists and 500 to clinical audiologists. Usable questionnaires total 136 for the former group and 266 for the latter. Some significant differences were found in the ways clinicians saw themselves as counselors and in the needs they perceived their patients as having. Respondents reported experiencing various methods of training and possessing diverse attitudes about the effectiveness of their preparation as counselors during their professional training. PMID- 1609860 TI - Reconstruction of old radical cavities. AB - Various techniques and materials have been proposed to deal with problems connected with radical cavities including recurrence of inflammatory processes, requirement of regular medication, social inconvenience (i.e., inability to practice any water sport, work in adverse environment, etc.). The present paper details the results of revalidation of old radical cavities using as filling a mixture of tricalcium phosphate and hydroxyapatite granules. Three techniques were used in reconstruction of the posterior canal wall. In the first procedure, the material was incorporated with fibrin adhesive to fill the cavity. In the other two methods the ceramic granules were covered respectively with a sheet of bone pate-fibrin sealant or with septal cartilage homografts. Twenty-four patients with chronic discharging old radical cavities were operated with anatomic results of 91.7 percent successful graft taken. The functional results showed an air-bone gap less than 30 dB in 72.7 percent of the cases after 6 months. After 2 years hearing gain was satisfactory in 63.6 percent of the patients. The different methods of reconstruction of posterior canal wall did not influence these findings. PMID- 1609861 TI - Facial Nerve Study Group: minutes of meeting--1991. PMID- 1609862 TI - Sex with former patients almost always unethical. PMID- 1609863 TI - The search: body, mind, and human purpose. AB - Psychiatry's appropriate agenda and severe distractions in sustaining it are presently a concern and have historically been so as we struggle with the issues of linking body, mind, and human purpose. Biology requires behaving, variability, and the development of regulations to implement "purpose" in coping with the milieu. Psychiatry begins and ends with our patients--with their diseases and dysfunctions, their biographies and aspirations--which, as a clinical medical science, we must systematically study. Doing that, we will borrow from and pose problems for all the life sciences. New knowledge about how cells and biological systems acquire, code, and exchange information challenges all of medicine. In assessing our advances and future, we consider the history of biological issues in psychiatry and the "sins" of biologism or reductionism. We will see that research questions and strategies in the current study of disease and therapeutics have not fundamentally shifted from Freud and Meyer to modern molecular neurobiology. The tension between the socially conditioned purposive self and impersonal biological processes is an inescapable intrinsic tension for psychiatry of which we must be cognizant as we continue the search. PMID- 1609864 TI - Mania in late life: focus on age at onset. AB - The authors review current understanding of manic syndromes and bipolar disorders in the elderly, emphasizing the limited number of systematic studies available. Discussion is focused on the validity of late age at onset as a nosologic distinction in geriatric patients. This issue is contrasted with possible age associated effects on early-onset illness. Data regarding incidence and prevalence in the elderly are assessed, and the high average age at onset of mania is noted. The review cites evidence that relatively low rates of familial affective disorder and increased frequency of certain diseases and drug use are associated with late age at onset. Aspects of psychopathology in the elderly, course of illness, and outcomes including chronicity, mortality, and cognitive impairment/dementia are considered. Management of these elderly patients is briefly discussed, highlighting questions concerning response to lithium salts. PMID- 1609865 TI - From nurture to network: examining links between perceptions of parenting received in childhood and social bonds in adulthood. AB - OBJECTIVE: The authors' goal was to consider the extent to which key characteristics of their parents influence children's later socialization in terms of social networks and intimate relationships and thus to examine whether there is evidence of such continuity. DATA COLLECTION: The authors reviewed the pertinent literature and then examined studies using a measure of key dimensions of the parenting received in childhood (the Parental Bonding Instrument) as well as measures of adult social networks. FINDINGS: The literature review revealed evidence of links (more evident in women) between perceptions of having received uncaring parenting and deficiencies in diffuse social bonds, which could reflect a causal process, a general response bias, or methodological limitations. By contrast, studies using the Parental Bonding Instrument and a specific measure of adult intimate bonds failed to find links between perceptions of parenting received in childhood and the quality of current intimate relationships unless there was extreme deprivation of parental care; in that case, the current intimate relationship was more likely to be rated as uncaring. CONCLUSIONS: These findings refine the view that early socialization experiences shape and dictate interpersonal relationships in adulthood. Any deficiencies in parent-child relationships, except, perhaps, gross parental deprivation, appear capable of modification by a range of experiences (particularly subsequent interpersonal relationships). PMID- 1609866 TI - AIDS/HIV risk behavior among the chronic mentally ill. AB - OBJECTIVE: There is growing concern that chronic mentally ill adults living in the community have a high risk for HIV infection. The purpose of this study was to identify risk knowledge, high-risk behaviors, and risk-related encounters of chronic psychiatric outpatients. METHOD: Detailed information on high-risk behaviors and risk-related situations during the past 12 months was collected from 60 outpatients appearing for regular visits at inner-city community mental health clinics. RESULTS: Of the 60 outpatients, 37 (62%) had been sexually active during the past year, and 42% of the men and 19% of the women reported multiple sexual contacts and infrequent use of condoms during intercourse. Assessments of the patients' knowledge of AIDS risks revealed substantial deficits in their practical understanding of AIDS and risk reduction measures. Although use of intravenous drugs was uncommon in this group, many subjects reported histories of 1) trading sex for money, drugs, or a place to stay, 2) coercion to engage in unwanted sex, 3) causal sexual encounters, and 4) sexual activity after use of drugs or intoxicants. Twenty percent of the subjects had met their sexual partners on the streets, in parks, or in other public places. One-third had been treated for sexually transmitted diseases other than AIDS. CONCLUSIONS: These findings underscore the need for AIDS risk assessment, counseling, and prevention programs for the chronic mentally ill. PMID- 1609867 TI - Evidence of dysfunction of a prefrontal-limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. AB - OBJECTIVE: The authors previously reported that in monozygotic twins discordant for schizophrenia the affected twin almost invariably had a smaller anterior pes hippocampus, measured with magnetic resonance imaging (MRI), and invariably had less regional cerebral blood flow (rCBF) in the dorsolateral prefrontal cortex during performance of the Wisconsin Card Sorting Test. The present study was an investigation of the relationship between hippocampal pathology and prefrontal hypofunction in the same twin pairs. METHOD: Nine pairs of monozygotic twins discordant for schizophrenia underwent MRI scanning for determination of anterior hippocampal volume and xenon-inhalation rCBF testing for determination of prefrontal physiological activation associated with the Wisconsin Card Sorting Test. RESULTS: The differences within twin pairs on the MRI and rCBF measures were strongly and selectively correlated. Specifically, the more an affected twin differed from the unaffected twin in left hippocampal volume, the more they differed in prefrontal physiological activation during the Wisconsin Card Sorting Test. In the affected twins as a group, prefrontal activation was strongly related to both left and right hippocampal volume. These relationships were not found in the group of unaffected twins. CONCLUSIONS: This finding is consistent with the notion that schizophrenia involves pathology of and dysfunction within a widely distributed neocortical-limbic neural network that has been implicated in, among other activities, the performance of cognitive tasks requiring working memory. PMID- 1609868 TI - Neuropsychological functioning of first-episode schizophreniform patients. AB - OBJECTIVE AND METHOD: This study compared 32 consecutively admitted first-episode schizophreniform patients, 26 patients with chronic schizophrenia according to the DSM-III-R criteria, and 25 normal comparison subjects on a comprehensive battery of neuropsychological tests to determine the degree of cognitive impairment existing at the onset of schizophrenic illness. Patients were tested within 2 weeks of admission to the hospital, after their medication had been stabilized. RESULTS: With age and education controlled, the first-episode and chronic patients performed significantly worse than the normal subjects on neuropsychological summary measures of executive function, verbal memory, spatial memory, concentration/speed, and global cognitive function and on left and right hemisphere function scales. The first-episode patients were as cognitively impaired as the chronic patients on all summary scales and many of the individual tests. Both groups showed relatively greater left than right hemisphere dysfunction. CONCLUSIONS: These findings suggest that substantial cognitive deficits, comparable to those of chronic patients, are present early in the course of psychotic illness. PMID- 1609869 TI - Long-term study of the sleep of insomnia patients with sleep state misperception and other insomnia patients. AB - OBJECTIVE: The objectives were 1) to investigate differences among patients with subjective insomnia (sleep state misperception), patients with objective findings of insomnia, and normal volunteers and 2) to assess the consistency of the sleep findings during a 2-month period. METHOD: Twenty-one subjects were studied. Subjects with sleep state misperception (N = 7) had insomnia complaints for more than 1 year, no objective sleep disturbance, and sleep efficiency of 90% or greater (on the diagnostic screening sleep recording), while subjectively estimating that sleep time was less than 6.5 hours. Subjects with objective insomnia (N = 7) met the same subjective criteria, but objectively sleep efficiency was 85% or less. Normal subjects (N = 7) had no insomnia complaints and objective sleep efficiency of 90% or greater. All subjects were recorded on 2 consecutive nights three times with a 3-week period between each pair of nights (6 standard all-night polysomnographic sessions of 8 hours). A subjective sleep questionnaire was administered after each sleep recording night. RESULTS: Sleep stage variables (percentages) were similar between the two insomnia groups, and both were different from the normal subjects. Sleep continuity variables were disturbed in the objective insomnia group, but they were similar in the sleep state misperception and normal groups. Both insomnia groups rated their sleep as inadequate on the questionnaires and differed from the normal subjects. The distinct sleep patterns of each of the three groups did not vary over the 6 nights of assessment. CONCLUSIONS: Sleep state misperception may be a prodromic or transitional state of sleep dysfunction between normal sleep and the sleep pattern of objective insomnia. PMID- 1609870 TI - Conservatorship for gravely disabled psychiatric patients: a four-year follow-up study. AB - OBJECTIVE: The authors examined the conservatorship process in California by studying a group of psychiatric patients for whom conservatorship was sought; their goal was to determine its effectiveness both during and after the period of conservatorship. METHOD: The subjects were 60 county psychiatric hospital inpatients 18-60 years old for whom temporary (30-day) conservatorships were obtained and who were followed for 4 years. The patients' courses over the 4 years were assessed in terms of whether 1-year conservatorships were obtained, stability (number and length of psychiatric hospitalizations, arrests, serious physical violence, and homelessness), and presence or absence of family support. RESULTS: The patients proved to be a severely mentally ill and disabled group. Thirty-five (58%) were granted a 1-year conservatorship sometime during the 4 year study period, and 25 (42%) were not. Both family support and conservatorship appeared to be related to the patients' stability. When one or both were present, there was a significantly greater likelihood of stability. CONCLUSIONS: The authors believe that for a considerable number of chronically and severely mentally ill individuals, conservatorship would play an important role in their clinical management and treatment by helping to eliminate their chaotic life styles, their cycle of admission and discharge from hospitals and jails, and/or their living on the streets, particularly when family support is absent. PMID- 1609871 TI - Differences in the effects of divorce on major depression in men and women. AB - OBJECTIVE: The authors examined the relationship between marital disruption and major depressive episodes. METHOD: The analyses were based on longitudinal, community-based data from the New Haven Epidemiologic Catchment Area (ECA) program on respondents 18-60 years old. The presence and history of major depression was assessed by using the National Institute of Mental Health Diagnostic Interview Schedule. RESULTS: Martial disruption was associated with higher prevalence rates of major depression in both men and women, but only men had a greater risk of a first-onset major depression. Differences between men and women in rates of major depression were observed only among married subjects. CONCLUSIONS: These findings suggest that the relationship between marital disruption and major depressive episode differs for men and women. They also provide further evidence that differences between men and women in rates of depression vary by marital status. PMID- 1609872 TI - Depression in patients with acute traumatic brain injury. AB - OBJECTIVE: This study was undertaken to examine patients with closed head injuries for the presence of depressive disorders. METHOD: A consecutive series of 66 patients with closed head injuries but no significant spinal cord or other organ system injury were examined by means of a semistructured psychiatric interview. The Hamilton Rating Scale for Depression as well as scales measuring impairment in activities of daily living, intellectual functioning, and social functioning were administered. The patients' CT scans were also examined. RESULTS: Seventeen patients had major depression and two had minor depression. The presence of left dorsolateral frontal lesions and/or left basal ganglia lesions and, to a lesser extent, parietal-occipital and right hemisphere lesions was associated with an increased probability of developing major depression. Compared to the nondepressed group, the group with major depression had a higher frequency of previous psychiatric disorder and showed evidence of poorer social functioning. CONCLUSIONS: Major depression occurs in about one-quarter of patients after traumatic brain injury. This is the same frequency as in other major disorders such as stroke. Major depression appears to be provoked by one or more factors that include poor premorbid social functioning and previous psychiatric disorder or injury to certain critical brain locations. PMID- 1609873 TI - Regional cerebral blood flow in childhood autism: a SPECT study. AB - OBJECTIVE: The authors investigated a possible cortical brain dysfunction associated with infantile autism. METHOD: They measured regional cerebral blood flow with single photon emission computed tomography (SPECT) and xenon-133 in 21 children with primary autism (according to DSM-III-R criteria). Five cortical brain areas including frontal, temporal, and sensory association cortices were examined in order to test the recent hypothesis of cerebral dysfunction in primary autism. Anatomical references for each subject were obtained with computerized tomography or magnetic resonance imaging and were used to delimit the regions of interest for SPECT analysis. RESULTS: When the results from the group with primary autism were compared with an age-matched group of nonautistic children with slight to moderate language disorders (N = 14), no cortical regional abnormalities were found. CONCLUSIONS: It appears that there is no regional cortical dysfunction in primary autism; however, in light of methodological limitations, one cannot exclude the possibility of more localized or subcortical brain dysfunctions in autism. PMID- 1609874 TI - Predictors of posttraumatic stress disorder after burn injury. AB - OBJECTIVE: The authors' goal was to examine subjective and objective predictors of posttraumatic stress disorder (PTSD). METHOD: Hospitalized burn patients were assessed 1 week after injury with both objective predictors (percent of burned area and facial disfigurement) and subjective predictors (emotional distress and perceived social support). The patients were then assessed 2, 6, and 12 months later for development of PTSD. RESULTS: Among 51 patients, 18 (35.3%) met PTSD criteria at 2 months. High rates of PTSD were also found at 6 months (N = 16, 40.0% of the 40 available patients) and 12 months (N = 14, 45.2% of the 31 available patients). PTSD was predicted by subjective variables assessed at baseline, but patients with more severe burns were not more likely to develop PTSD. CONCLUSIONS: The DSM-III-R diagnosis of PTSD relies on an objective evaluation of the stressor's severity. The prospective data in this study support those who argue that evaluations of the severity of the stressor might also take into account subjective factors. PMID- 1609875 TI - Effectiveness of a meditation-based stress reduction program in the treatment of anxiety disorders. AB - OBJECTIVE: This study was designed to determine the effectiveness of a group stress reduction program based on mindfulness meditation for patients with anxiety disorders. METHOD: The 22 study participants were screened with a structured clinical interview and found to meet the DSM-III-R criteria for generalized anxiety disorder or panic disorder with or without agoraphobia. Assessments, including self-ratings and therapists' ratings, were obtained weekly before and during the meditation-based stress reduction and relaxation program and monthly during the 3-month follow-up period. RESULTS: Repeated measures analyses of variance documented significant reductions in anxiety and depression scores after treatment for 20 of the subjects--changes that were maintained at follow-up. The number of subjects experiencing panic symptoms was also substantially reduced. A comparison of the study subjects with a group of nonstudy participants in the program who met the initial screening criteria for entry into the study showed that both groups achieved similar reductions in anxiety scores on the SCL-90-R and on the Medical Symptom Checklist, suggesting generalizability of the study findings. CONCLUSIONS: A group mindfulness meditation training program can effectively reduce symptoms of anxiety and panic and can help maintain these reductions in patients with generalized anxiety disorder, panic disorder, or panic disorder with agoraphobia. PMID- 1609876 TI - Onset of obsessive-compulsive disorder in pregnancy. AB - OBJECTIVE: Although the role of pregnancy and childbirth in postpartum psychosis and depression has been studied, the association between pregnancy and obsessive compulsive disorder has not been specifically addressed. The authors evaluated the role of pregnancy in the onset of obsessive-compulsive disorder. METHOD: Female patients with obsessive-compulsive disorder (N = 106) completed a questionnaire assessing age at onset of symptoms, marital status, number of children, age at each pregnancy, and life events associated with the onset of obsessive-compulsive disorder. RESULTS: Of the 106 women, 42 were childless and 59 had at least one child each; five others were also childless but had had abortions (N = 4) or a miscarriage (N = 1). Of the 42 women without children, 12 (28.6%) had first experienced obsessive-compulsive symptoms between the ages of 13 and 15 years, but there were two peaks of onset for the women with children: ages 22-24 and 29-32 years. Of the 59 patients with children, 23 (39.0%) had experienced symptom onset during pregnancy; this was the first pregnancy for 12, the second pregnancy for eight, and the third pregnancy for three. Four of the five women who had had abortions or a miscarriage had experienced the onset or an exacerbation of obsessive-compulsive symptoms during pregnancy. CONCLUSIONS: The association between pregnancy and the onset of obsessive-compulsive symptoms in these female patients highlights the need for further research on psychological and biological factors associated with pregnancy and obsessive-compulsive disorder. PMID- 1609877 TI - Psychiatry and the homeless mentally ill: a reply to Dr. Lamb. AB - Homeless mentally ill persons are highly visible subjects of ongoing public discussion and potent symbols of a host of contemporary social problems. They present psychiatry with a scientific challenge that calls for further elucidation of the sources of their mental illness and for fashioning possible solutions to their problems. They also present a moral challenge that requires psychiatrists to acknowledge the cultural, political, legal, and economic context of the mental problems of the homeless in the course of deciding what should be done to help them. H. Richard Lamb has proposed a program of aggressive outreach and psychiatric hospitalization for the homeless mentally ill. The authors believe that his proposal misconstrues the problems and needs of homeless mentally ill individuals; it would also needlessly infringe upon their freedom, further stigmatize them, and probably not help them. The authors offer an alternative understanding of the plight of the homeless mentally ill which places their problems within a larger context of social trends and domestic issues that society has been reluctant to confront. Psychiatrists can help the homeless mentally ill by championing their liberty rights and by focusing public discourse on the broad national need for improved access to medical and psychiatric care. PMID- 1609878 TI - Regulation of appetite and cholecystokinin secretion in anorexia nervosa. AB - Six patients with anorexia nervosa, the same patients after weight normalization, and six healthy control subjects had similar fasting and postprandial plasma cholecystokinin concentrations. These data do not support the hypothesis that low levels of hunger and food intake in anorexic patients reflect hypersecretion of this endogenous hormone, which is thought to inhibit hunger, promote satiety, and reduce feeding. PMID- 1609879 TI - Replication of action of cholecystokinin tetrapeptide in panic disorder: clinical and behavioral findings. AB - Eleven patients with panic disorder were challenged with cholecystokinin tetrapeptide (CCK-4) on two occasions. The effects of CCK-4 were consistent except symptom onset was more rapid with the second injection. Demonstrating that the effects of CCK-4 are reproducible in panic patients opens the doors for studies of the effects of drug treatment on CCK-4-induced panic. PMID- 1609880 TI - Somatic symptoms after a natural disaster: a prospective study. AB - The authors prospectively examined the prevalence of somatization symptoms among community respondents after a natural disaster in Puerto Rico. Exposure to the disaster was related to a higher prevalence of medically unexplained physical symptoms, particularly gastrointestinal ones (abdominal pain, vomiting, nausea, excessive gas) and pseudoneurological ones (amnesia, paralysis, fainting, unusual spells/double vision). PMID- 1609881 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609882 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609883 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609885 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609884 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609886 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609888 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609887 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609889 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609890 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609891 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609892 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609893 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609894 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609895 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609896 TI - Psychotherapist-patient sexual contact after termination of treatment. PMID- 1609897 TI - Tranylcypromine abuse: cause for concern? PMID- 1609898 TI - Dynamic cognitive therapy anyone? PMID- 1609899 TI - Young women's antisocial behavior and the later emotional and behavioral health of their children. AB - OBJECTIVES: Antisocial and criminal behavior are increasing among US youth, especially among females. Thus, questions arise concerning whether youthful female deviant behavior eventually will have negative behavioral and emotional consequences for the later children of these women. METHODS: Associations between the severity of early female antisocial behavior (including both drug-related and non-drug related offenses) and the later behavioral and emotional health of the children of these women were examined among 1425 mother-child pairs of the National Longitudinal Survey of Youth. RESULTS: Multiple linear regression procedures indicated a significant positive relationship between the severity of the mothers' early non-drug-related offenses and the later severity of the children's scores on the Antisocial, Hyperactive, Anxious/Depressed, Headstrong, Peer Conflict/Social Withdrawal, Immature Dependency, and Total Problem subscales of the Behavior Problem Index. CONCLUSIONS: This study demonstrated an association between the antisocial behavior of female youth and the later behavioral and emotional problems of the children of these women. Future research needs to determine the mechanisms underlying the intergenerational transmission of these types of problems so that effective preventive and therapeutic public health practices may be designed and implemented. PMID- 1609900 TI - Rotating shift work, sleep, and accidents related to sleepiness in hospital nurses. AB - A hospital-based survey on shift work, sleep, and accidents was carried out among 635 Massachusetts nurses. In comparison to nurses who worked only day/evening shifts, rotators had more sleep/wake cycle disruption and nodded off more at work. Rotators had twice the odds of nodding off while driving to or from work and twice the odds of a reported accident or error related to sleepiness. Application of circadian principles to the design of hospital work schedules may result in improved health and safety for nurses and patients. PMID- 1609901 TI - Birthweight distributions in Mexico City and among US Southwest Mexican Americans: the effect of altitude. AB - In this study birthweight distributions for Mexican Americans and Mexico City were compared. Sharp differences in the two distributions were nearly eliminated by controlling for altitude. The small remaining excess in low birthweight in Mexico City appears to be due to a slight overrepresentation of tertiary hospital deliveries, and possibly to a greater prevalence of pathological conditions. The results are consistent with the favorable low birthweight rate reported for Mexican Americans and illustrate the need to adjust for altitude in studies of low birthweight. PMID- 1609902 TI - Identification of nonfatal family and intimate assault incidents in police data. AB - We examined different strategies for identifying nonfatal family and intimate assaults (FIAs) in police data. Police most often classify such incidents in the "assault" category, but they also use other crime categories. We estimated that, during 1984, 3300 FIAs (or 837 per 100,000 population) occurred in Atlanta. Of those, 77% were classified as assaults; 23% were classified in nonassault categories. Research measuring the magnitude of FIAs should take into account incidents classified in nonassault crime categories. PMID- 1609903 TI - The cost and frequency of hospitalization for fall-related injuries in older adults. AB - Using a population-based hospital discharge registry with E codes, we examine the 1989 hospitalizations of older adults in Washington State for fall-related injuries. Fall-related trauma accounted for 5.3% of all hospitalizations of older adults, with hospital charges totaling $53,346,191, and resulted in discharge to nursing care more often than other such hospitalizations. An annual hospitalization rate of 13.5 per 1000 persons and an annual cost of $92 per person is reported. The importance of preventing fall-related injuries in older adults is discussed. PMID- 1609904 TI - Carcinogens in tobacco smoke: benzo[a]pyrene from Canadian cigarettes and cigarette tobacco. AB - We evaluated the benzo[a]pyrene (BaP) content in the smoke from 35 brands of Canadian cigarettes and 5 brands of Canadian tobaccos for roll-your-own cigarettes. For the cigarettes, mean values of BaP ranged from 3.36 ng to 28.39 ng per cigarette, roughly in proportion with declared tar values. The relationship between declared tar and yields of BaP, however, does not allow accurate prediction of one from the other. For the tobaccos, mean BaP values ranged from 22.92 ng to 26.27 ng (average, 24.7 ng) per cigarette. The implications of these findings are discussed with respect to overall exposure. PMID- 1609905 TI - Discrepancies between self-reported smoking and carboxyhemoglobin: an analysis of the second national health and nutrition survey. AB - Environmental, self-report, and demographic factors mediated the relationship between self-reported cigarette smoking and carboxyhemoglobin among 2114 smokers and 3918 nonsmokers. Self-reported nonsmokers with carboxyhemoglobin levels between 2% and 3% were more likely to be self-reported ex-smokers, to live in a larger community, and to be younger, less educated, and male than were self reported nonsmokers with carboxyhemoglobin levels of less than 2%. Self-reported nonsmokers with strong evidence of cigarette consumption (carboxyhemoglobin level greater than 3%) were more likely to be self-reported ex-smokers, younger, less educated, and non-White than were nonsmokers with carboxyhemoglobin levels of less than 2%. PMID- 1609906 TI - Recall of AIDS public service announcements and their impact on the ranking of AIDS as a national problem. AB - The efficacy of two public service announcements from Phase V of the "America Responds to AIDS" (ARTA) campaign was assessed at two sites. Participants were randomly assigned to view a local news program, one with an ARTA public service announcement appearing six times and the other with no AIDS public service announcements. During telephone interviews with 907 participants 1 to 3 nights after viewing, 21% at Site A and 59% at Site B could correctly recall the ARTA public service announcements. Absolute mentions of AIDS as an important national issue increased. PMID- 1609907 TI - The President's Committee on Health Education: a 20-year retrospective on its politics and policy impact. AB - The President's Committee on Health Education was created by Richard M. Nixon in September 1971 and submitted its final report in September 1973. The committee resulted from the convergence of (1) a perceived national domestic policy need in response to escalating medical costs, (2) Nixon's personal and political ambitions, and (3) the dynamic political context of the late 1960s and early 1970s. Its work led to both private and public initiatives designed to influence the public's health through education; its findings and recommendations also laid the foundation for the National Consumer Health Information and Health Promotion Act of 1976 and thus contributed significantly to the development of subsequent national policy in health promotion and disease prevention. This paper places the work and contributions of the committee into historical perspective by analyzing the committee's origins and methods and the underlying politics that shaped its work and final report. The impact of the President's Committee is traced from the emergence of health education in the early 1970s as a potentially cost-effective alternative to medical care to the pivotal role health education now plays in health promotion and disease prevention efforts. PMID- 1609908 TI - Eligibility for Indian Health Service programs revisited. PMID- 1609909 TI - Cocaine use in obstetric patients underreported. PMID- 1609910 TI - The quality of computerized hospital discharge data. PMID- 1609911 TI - Determinants of worldwide health. PMID- 1609912 TI - Health and the environment in the 1990s. AB - Expectation of life at birth provides a simple measure of the state of health of a country. Differences in the expectation are examined in the United States over time and between males and females and Whites and non-Whites, and worldwide between market and nonmarket developed countries, and between developed and developing countries. The principal factors responsible for the trends and the current differences are changes in the social and physical environment, in personal behavior, and in medical care, and their relative importance is assessed. It is concluded that, at present, the principal environmental hazards worldwide are those associated with poverty of individuals within the market economies and of communities in the developing countries and that in the future, they will be the effects of overpopulation and the production of greenhouse gases. PMID- 1609913 TI - Commentary: environmental disease--a preventable epidemic. AB - Toxic environmental diseases are highly preventable causes of morbidity and mortality. Toxic diseases in the work environment cause an estimated 50,000 to 70,000 deaths and 350,000 new cases of illness each year in the United States; the asbestos pandemic will ultimately claim at least 300,000 lives; pediatric lead poisoning is epidemic, and an estimated 3 to 4 million US preschool children have blood lead levels above 10 micrograms/dl and could suffer long-term neuropsychological impairment. Prevention of environmental diseases can be achieved through legislation and regulation that control common-source exposures to chemical toxins. Modification of personal behaviors, such as tobacco and alcohol consumption, complements but does not replace control of toxic environmental exposures. PMID- 1609914 TI - The potential impact of epidemiology on the prevention of occupational disease. AB - This presentation reviews occupational epidemiology as a foundation for workplace disease prevention activities. By examining descriptive, etiologic and intervention occupational epidemiology studies, a range of opportunities are illustrated where epidemiology has played, or could play a principal role in guiding preventive efforts. Descriptive studies presented include ones based on vital records, on epidemic investigations, cross-sectional surveys, and surveillance. Etiologic studies review the largely successful development of knowledge for lung cancer and asbestos exposure for pulmonary effects of isocyanate exposures. However, attention is also directed to the need for etiologic studies of work environment risks for both cardiovascular and musculoskeletal disease. Finally importance is placed on the too infrequent epidemiologic studies of intervention. Historical examples of control of large risks from nickel cancers and silicosis are balanced with more recent examples of successes at reducing smaller risks of cardiovascular disease and oil acne. Throughout, emphasis is placed on the importance of reintegrating the academic discipline of epidemiology into the application of study findings to prevention of workplace risks. PMID- 1609915 TI - Surveillance data on US coal miners' pneumoconiosis, 1970 to 1986. AB - OBJECTIVES: Statistics on prevalence of pneumoconiosis among working underground coal miners from data collected as part of a large national radiographic surveillance program between 1970 and 1986 are presented. The main intent was to examine the time-related trend in prevalence over this period, which coincides with historically low dust levels mandated by federal act. METHODS: Tenure specific prevalence rates and summary statistics derived from them for four consecutive time intervals within the 16-year period were calculated and compared. RESULTS: The results indicate a reduction in pneumoconiosis over the life of the program. This trend is similar to that seen in epidemiologic studies undertaken concurrently. CONCLUSIONS: Although low participation in the surveillance program and other problems complicate the findings, it appears that reductions in dust exposure mandated by federal act in 1969 have led to lower prevalence of pneumoconiosis among underground coal miners. PMID- 1609916 TI - British data on coal miners' pneumoconiosis and relevance to US conditions. AB - OBJECTIVES: The current primary federal dust standard for US underground coal miners of 2 mg/m3 respirable dust is based on British epidemiological information on exposure-response derived in 1969. Since then, much new information has become available. This paper reviews and compares the available information as it relates to the US mining situation. METHODS: Recent exposure-response information on pneumoconiosis and dust exposure derived by British researchers was employed to estimate working-life risks of pneumoconiosis for miners exposed to 2 mg/m3. RESULTS: It is estimated that close to 9% of underground coal miners who work for 40 years in a 2 mg/m3 environment would develop pneumoconiosis (category 1 or greater). Progressive massive fibrosis would develop in 0.7%. CONCLUSIONS: There are unresolved questions relating to the validity of extrapolating findings on British mines and miners to the US and also in predicting disease levels at the low end of the dust exposure spectrum. Given the data available, current information suggests miners who are employed for a working life-time at the current federal dust limit of 2 mg/m3 are still at risk of developing pneumoconiosis. PMID- 1609917 TI - Job strain and prevalence of hypertension in a biracial population of urban bus drivers. AB - OBJECTIVES: In this study we tested the association between occupational stress- as measured by job demands, decision latitude, and job strain--and hypertension in a population of 1396 Black and White bus drivers. METHODS: Height, weight, blood pressure, and medical history were assessed by physical exam. Drivers completed a questionnaire assessing their work schedules, personal habits, and self-perceptions about job demands and decision latitude. RESULTS: Univariate analyses revealed significant inverse associations; lower levels of job demands and job strain were associated with a higher prevalence of hypertension for Blacks and Whites. After 12 confounding variables were controlled for, the association between these two measures of occupational stress and hypertension became nonsignificant. Decision latitude was also not significantly associated with hypertension. CONCLUSIONS: Our findings are inconsistent with previous studies' findings of a positive association between job strain and chronic diseases. The difference in results may be explained by our incorporation of individuals' perceptions in the measurement of occupational stressors and our use of individuals from a single occupation with comparable job responsibilities and income, thus controlling for potential confounding by social class. PMID- 1609918 TI - Use of hair coloring products and the risk of lymphoma, multiple myeloma, and chronic lymphocytic leukemia. AB - OBJECTIVES: Hair coloring products are widely used and contain components that are mutagenic and carcinogenic. An association between occupational exposure to hair coloring products and hematopoietic cancers has been reported, but the risk for these cancers among users has not been carefully evaluated. METHODS: We conducted a population-based, case-control study with telephone interviews from 385 with telephone interviews from 385 non-Hodgkin's lymphoma cases, 70 Hodgkin's disease cases, 72 multiple myeloma cases, 56 chronic lymphocytic leukemia cases, and 1432 controls. RESULTS: Among women, use was associated with odds ratios of 1.5 for non-Hodgkin's lymphoma, 1.7 for Hodgkin's disease, 1.8 for multiple myeloma, and 1.0 for chronic lymphocytic leukemia. Risk was higher for permanent hair coloring products than for semi- or nonpermanent products, particularly for dark colors. Long duration and early age of first use tended to increase risk, but the patterns were inconsistent. Use was much less common in men and did not significantly increase risk. CONCLUSIONS: The use of hair coloring products appears to increase the risk of non-Hodgkin's lymphoma. Multiple myeloma and Hodgkin's disease were also associated, although based on far fewer subjects. If these results represent a causal association, use of hair coloring products would account for 35% of non-Hodgkin's lymphoma cases in exposed women and 20% in all women. PMID- 1609920 TI - Ideal aid in the Pacific. PMID- 1609919 TI - Education, race, and high-density lipoprotein cholesterol among US adults. AB - OBJECTIVES: Although educational achievement is positively related to levels of high-density lipoprotein cholesterol (HDL-C) among White adults, there is an inverse association among Blacks. We assessed whether this interaction could be attributed to differences in the relation of education to correlates of HDL-C. METHODS: Cross-sectional analyses were based on data from 8391 White and 995 Black adults who participated in the Second National Health and Nutrition Examination Survey. RESULTS: Associations between education and HDL-C levels varied from negative (Black men), to nearly nonexistent (White men and Black women), to positive (White women). Mean HDL-C levels were higher among Blacks than among Whites, but differences varied according to educational achievement. Among adults with less than 9 years of education, mean levels were 6 to 10 mg/dL higher among Blacks, but the radical difference was less than 1 mg/dL among adults with at least 16 years of education. About 20% to 40% of these differences could be accounted for by obesity, alcohol consumption, and other characteristics. CONCLUSIONS: Because of the implications for coronary heart disease risk, consideration should be given to behavioral characteristics associated with the interaction between race and educational achievement. PMID- 1609921 TI - Plastic ampoules. PMID- 1609922 TI - Propofol vs methohexitone. PMID- 1609923 TI - LMA and swallowing. PMID- 1609924 TI - The laryngeal mask airway--use in the management of stridor. PMID- 1609925 TI - Supplemental oxygen using an LMA. PMID- 1609926 TI - The laryngeal mask for failed intubation at caesarean section. PMID- 1609927 TI - The laryngeal mask airway for anaesthesia in the prone position. PMID- 1609928 TI - Whitacre 22-gauge spinal needle in young patients. PMID- 1609929 TI - Interpleural analgesia: open insertion of catheter. PMID- 1609930 TI - Anaesthetic management for pancreatic stimulation test. PMID- 1609931 TI - Disappearing epidural catheters. PMID- 1609932 TI - Evaluation of the Bair Hugger warming device. PMID- 1609933 TI - Rectal indomethacin. PMID- 1609934 TI - Presumed carbon dioxide embolism associated with hysteroscopy. PMID- 1609935 TI - Patient-controlled epidural analgesia in labour--is a continuous infusion of benefit? AB - A randomised, single-blind study was conducted among 52 gravida in active labour, to investigate two variants of patient-controlled epidural analgesia--bolus only versus bolus plus infusion. Patient-controlled analgesia variables, using an epidural solution of 0.125% bupivacaine plus fentanyl 3 mcg per ml, were a 4 ml incremental bolus with 15 minute lockout, plus or minus a 4 ml per hour infusion. Up to three additional staff-administered supplements of 0.5% bupivacaine 4 ml (20 mg) were allowed. There was no significant difference between groups with respect to pain relief, supplementary boluses required, satisfaction, side effects or details of patient-controlled epidural analgesia, with the exception of greater fentanyl usage in the bolus plus infusion group (P less than 0.003). Both groups had high quality analgesia, low rates of bupivacaine usage and were highly satisfied. However, under the conditions of the study, the addition of a continuous background infusion to self-administration conferred no benefit. PMID- 1609936 TI - Haemodynamic effects and uptake of enflurane in patients undergoing cardiac surgery: good versus poor myocardial function. AB - We measured haemodynamic effects and uptake of enflurane in patients undergoing cardiac surgery utilizing a standard anaesthetic technique of fentanyl 15 mcg/kg nitrous oxide 50%/enflurane 1%. We divided 22 patients preoperatively into two groups according to standard criteria: good and poor myocardial function. Regression lines could be drawn illustrating the relationship of cardiac output and uptake (at 1 minute: r = -0.56, P less than 0.01; at 5 minutes: r = -0.43, P less than 0.05; at 30 minutes: r = -0.31, P = 0.08). Although patients with poor myocardial function had decreased uptake of enflurance (approximately 10-20%), this did not reach statistical significance. Fentanyl/nitrous oxide/enflurane anaesthesia provided stable haemodynamics, even in patients with poor myocardial function. Both groups had a shunt fraction of approximately 10% and an arterial: end-tidal carbon dioxide difference of approximately 3-4 mmHg. PMID- 1609937 TI - The cardiovascular and haematological effects of purified prothrombin activator from the common brown snake (Pseudonaja textilis) and their antagonism with heparin. AB - The cardiovascular and haematological effects of purified prothrombin activator derived from the venom of the Australian Common Brown Snake (Pseudonaja textilis) were studied in anaesthetised, mechanically ventilated dogs. Severe depression of systemic blood pressure and cardiac output and a rise in central venous pressure were observed. Thrombocytopenia, prolongation of both prothrombin time and activated partial thromboplastin time and a reduction in serum fibrinogen were also observed. All of these observed effects were prevented by the prior administration of heparin--a naturally occurring anticoagulant. We conclude that the prothrombin activator in Pseudonaja textilis venom may cause cardiovascular depression due to myocardial dysfunction secondary to disseminated intravascular coagulation. PMID- 1609938 TI - The efficacy of heparin in the treatment of common brown snake (Pseudonaja textilis) envenomation. AB - The efficacy of heparin therapy after subcutaneous injection of Common Brown Snake (Pseudonaja textilis) venom was studied in anaesthetised, mechanically ventilated dogs. Intravenous heparin (100 U/kg), administered fifteen minutes after envenomation, neither prevented nor hastened the recovery from cardiovascular depression and coagulopathy observed after venom administration. Heparin therapy is not recommended for the treatment of established human envenomation. PMID- 1609939 TI - Is fentanyl effective for postoperative analgesia in day-surgery? AB - Fentanyl is commonly used as an adjunct to general anaesthesia for day-surgery procedures. We have prospectively studied the effect of this practice on postoperative analgesia in 304 day-surgery patients, 164 undergoing termination of pregnancy and 140 having various other minor gynaecological procedures. Approximately half the patients received fentanyl, the mean dose being 50 mcg. Fentanyl given during anaesthesia had no effect during recovery on analgesic requirements or on nausea or vomiting in either pregnant or non-pregnant patients. PMID- 1609940 TI - Comparison of epidural and intravenous opioid analgesia after elective caesarean section. AB - Patient acceptance is a particularly relevant method of assessing currently employed epidural and intravenous techniques of opioid analgesia after elective caesarean section. We have prospectively studied 71 such patients, randomised postoperatively to receive epidural morphine, intravenous morphine or intravenous pethidine. When compared with either intravenous opioid, epidural morphine provided twofold better average or excellent analgesia with 30% less drowsiness but with about 50% more pruritus. In spite of this troublesome complication, more patients (83% vs 74%) preferred epidural to intravenous opioid analgesia. PMID- 1609941 TI - A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. AB - This double-blind randomised study compared postoperative analgesia after a loading regimen of methadone or morphine in thirty women undergoing abdominal hysterectomy. Methadone or morphine, 0.25 mg.kg-1, was given intravenously at induction of anaesthesia with further increments in the recovery room for analgesia if required. The mean (SD) total doses of methadone and morphine required were 0.43 (0.13) mg.kg-1 and 0.45 (0.15) mg.kg-1 respectively. Patients in the methadone group had lower pain scores in the subsequent 48 hours (P less than 0.001) and required less supplementary intramuscular opioids (P less than 0.001). Ten patients in the methadone group did not request any further opioid analgesics while all patients in the morphine group made at least two requests for opioids. The overall postoperative course was remembered as less painful by patients in the methadone group (P less than 0.001). There was no significant respiratory depression or excessive sedation in either group. PMID- 1609942 TI - Inter-ethnic differences in postoperative pethidine requirements. AB - A preliminary study of 24 hours' postoperative analgesia using a patient controlled analgesia technique was undertaken in eight European and fourteen Asian adult patients. All patients had upper abdominal surgery and received weight-related doses of pethidine postoperatively via a Cardiff Palliator. Both groups had a similar degree of analgesia as assessed by visual analogue score but the Asian patients were more sedated in the postoperative period. The Asian patients made 24% fewer demands for analgesia and had a smaller mean (SD) pethidine consumption, 7.62 (2.04) mg.kg-1, compared with the European patients, 9.97 (2.14) mg.kg-1, (P less than 0.05) during the first 24 hours. Further research is necessary to determine whether the smaller requirement for analgesia in Asian patients is a result of pharmacokinetic or pharmacodynamic differences. PMID- 1609943 TI - Management of theophylline overdose patients in the intensive care unit. AB - In a retrospective survey of all adults admitted to the Intensive Care Unit with acute theophylline poisoning over the last five years, we identified 38 patients (6.8% of all admissions for poisoning), two of whom died. Thirty-five (92%) had taken a sustained-release preparation. Eight patients had grand mal seizures and six developed arrhythmias (ventricular fibrillation, 3; atrial fibrillation, 2; supraventricular tachycardia, 1). Severe vomiting was present in 34 (89%) and proved to be a serious obstacle to the administration of enteral charcoal. The vomiting was controlled by intravenous metoclopramide in seventeen patients (50%), but the remaining seventeen required mechanical ventilation with sedation and muscle relaxation for the effective delivery of nasogastric charcoal. Importantly, in nine (24%), the serum theophylline concentration continued to rise despite enteral charcoal. Charcoal haemoperfusion was used in seven (18%). We present an algorithm for the management of severe, acute theophylline poisoning. PMID- 1609944 TI - Time-dependent error in the APACHE II scoring system. AB - Using the APACHE II scoring system, the risk of death was calculated for 189 patients in the Wanganui Intensive Care Unit and 194 patients in the Harare Intensive Care Unit. Using tables of actual and predicted outcome, the predictive power of the system was compared in patients grouped according to the length of time that they spent in the ICU. The predictive error increased from 15% in those patients staying less than six days, to 38% in those staying six days or more (P less than 0.01). The predictive accuracy of the APACHE II system appeared to decrease with the length of time the patient stayed in the Intensive Care Unit. PMID- 1609945 TI - A blind guided technique for placing double-lumen endobronchial tubes. AB - A new technique is described to aid in achieving a correct blind insertion of an endobronchial tube. The tube is selected by length to fit the distance from the patient's mouth to carina. As the tube is inserted, the position of the endobronchial cuff is monitored. This is done by inflating the bronchial cuff in the trachea and after each breath, advancing the tube down the trachea until only one lung is inflated. This accurately identifies the bronchial cuff as just beyond the carina, at the entrance to the main bronchus. From here, the tube can be advanced precisely into the bronchus to give the optimal conditions for isolation of the right and left lungs. PMID- 1609946 TI - Hydrothorax as a late complication of central venous catheterization in children: diagnosis and management. PMID- 1609947 TI - The missing wire--a complication of central venous catheterization. PMID- 1609948 TI - Severe localised bronchospasm in a young asthmatic patient during thoracotomy. PMID- 1609949 TI - Coma and thyroid dysfunction. PMID- 1609950 TI - Chromobacterium violaceum septicaemia: the intensive care management of two cases. AB - The first human infection with Chromobacterium violaceum was recorded in 1927, but since then there have been about 33 cases reported worldwide, including two from Australia. Chr. violaceum occurs in the tropics and subtropics and is generally considered to be nonpathogenic, but infection can occur in patients who are immunosuppressed and it has a high mortality rate. This paper presents the intensive care management of two cases of Chr. violaceum infection occurring in Far North Queensland. The patients' predisposition appears to have been malnourishment and alcohol abuse. The increased use of immunosuppressive drugs and the appearance of diseases such as acquired immune deficiency syndrome (AIDS) make it possible that we will see more of this condition in Australian intensive care units. PMID- 1609952 TI - Pneumomediastinum and subcutaneous emphysema following spinal surgery. PMID- 1609951 TI - Oral midazolam is an effective premedication for children having day-stay anaesthesia. AB - The effect of oral premedication was studied in a double-blind, randomised trial of 200 children undergoing day-stay anaesthesia. Midazolam 0.25 mg/kg, midazolam 0.5 mg/kg, diazepam 0.5 mg/kg or a placebo was given orally one hour prior to anaesthesia. Patient state was assessed at nine stages, from administration of the premedication up to and including induction of anaesthesia, using a four point behavioural scale. Patient state was also assessed postoperatively in the recovery area and the day-stay ward. There was no difference between the four groups until induction of anaesthesia. At this stage 82% of children were either asleep or awake and calm. Patients who received midazolam 0.5 mg/kg were more likely to be asleep or awake and calm at induction rather than other groups (P = 0.05). Children receiving midazolam 0.5 mg/kg or diazepam 0.5 mg/kg slept longest in the post anaesthetic recovery room (P less than 0.005), and spent most time there (P less than .005). There was no difference between groups in the length of time spent in the day-stay ward or in the number of overnight admissions. The study shows that a high proportion of unsedated children are calm at induction of anaesthesia and that oral midazolam is an effective premedication in children for day-stay anaesthesia. PMID- 1609953 TI - Acute pharyngolaryngeal oedema and pre-eclamptic toxaemia. PMID- 1609954 TI - Monitoring cholesterol autoxidation processes using multideuteriated cholesterol. AB - Deuterium-labeled cholesterol is used to monitor for artifactually produced cholesterol oxidation products during analysis. [2H9]Cholesterol, labeled on the side chain, is added to the sample immediately upon isolation, and the ratios of labeled to unlabeled oxides and of labeled to unlabeled cholesterol are monitored by capillary gas chromatography-mass spectrometry. The analytical methodology involves an initial solvent extraction followed by silica gel LC and reversed phase HPLC to isolate and concentrate the oxide fraction. The feasibility of the technique for analysis of cholesterol oxides in foods and biological samples at the part per million level with an accuracy of better than +/- 5% is demonstrated. PMID- 1609955 TI - High sensitivity tracer detection using high-precision gas chromatography combustion isotope ratio mass spectrometry and highly enriched [U-13C]-labeled precursors. AB - The use of highly enriched, uniformly labeled fatty acid ([U-13C]) with analysis by high-precision gas chromatography-combustion isotope ratio mass spectrometry (GCC-IRMS) has been evaluated as a metabolic tracer technique. 13C/12C ratios are routinely determined to precisions (SD) of less than 0.00001 (delta PDB less than 1/1000) for greater than 10 ng of fatty acid, and less than 0.001 (delta PDB less than 100/1000) for samples of 30 pg of fatty acid, the latter corresponding to a 100-fmol sample. Baseline fatty acid 13C/12C in human plasma fractions is shown to fluctuate not more than 0.000 04 (delta PDB 4/1000) over 10 h. 13C/12C enrichments greater than 0.001 (delta PDB 100/1000) are obtained in a fatty acid plasma fraction subsequent to a 10-mg dose of 42% 13C-labeled stearic acid to a 78-kg adult. Biokinetics are discerned over an 13C/12C enrichment range of less than 0.0002 (approximately 13/1000 in delta PDB units) in plasma. A means for correction of isotope ratio contamination due to carbon-containing derivatives is presented. High-precision GCC-IRMS used in concert with highly enriched tracers is shown to possess advantages versus organic GC/MS for stable isotopic tracer detection and is superior to radiotracer methods in terms of dose sizes and analysis efficiency. PMID- 1609956 TI - Enzyme-based bilayer conducting polymer electrodes consisting of polymetallophthalocyanines and polypyrrole-glucose oxidase thin films. AB - Bilayer conducting polymer electrodes, which consist of a polymetallophthalocyanine (PMePc) and polypyrrole incorporating glucose oxidase (PPy-GOx), were prepared on the glassy-carbon electrode by the successive electrochemical deposition of two different polymers. The bilayer film electrodes showed catalytic behavior, which included an enhanced amperometric response current with the substrate and a significantly shifted oxidation potential (approximately 700 mV) of the response current. The bilayer electrodes also showed a fast response time and good stability with the substrate. A bilayer microelectrode, which was prepared by using both PCuPc and PPy-GOx polymer films, also showed a good amperometric response with the substrate. PMID- 1609957 TI - Urinary cotinine fluoroimmunoassay for smoking status screening adapted to an automated analyser. AB - A polarization fluoroimmunoassay for cotinine, a major metabolite of nicotine, has been adapted for fully automated screening of urine samples on the Abbott TDx analyser. The method has sensitivity and specificity suitable for the discrimination of active smokers from non-smokers (including passive smokers) by application of a cut-off at 0.5 mg l-1 of total urinary cotinine. Most active smokers' urine gave results over 1 mg l-1, whereas apparent levels in non-smokers were 0.08 mg l-1 or lower. A result for one sample can be obtained in about 5 min and a throughput of 80 samples h-1 can be maintained for large-scale screening applications. PMID- 1609958 TI - Peculiarities of the distribution of man-made radionuclides in several European seas. AB - Results of a study on the distribution of the man-made radionuclides 137Cs and 90Sr in the surface waters of several European seas are presented. Based on an analysis of the ratio of these two radionuclides, an attempt was made to isolate the 'Chernobyl water' and to estimate the contribution of 'Chernobyl radioactivity' to the total radioactivity in the waters of the seas investigated. PMID- 1609959 TI - Morphological analysis of abnormal digital chondrogenesis in the brachypod (bpH) mouse limb in organ culture. AB - Brachypod (bpH/bpH), an autosomal mutation in mice, is characterized by a shortening of the long bones and paws, and a delay or absence of ossification in some of the distal limb elements. The present study represents a detailed description of the brachypod phenotype in day 12 hindlimb buds maintained for 6 days in a submerged, serum-free organ culture system. Using this in vitro system, the proximal-to-distal effect on the severity of cartilage reduction was intensified in the brachypod explants with an intermediate expression in the heterozygotes. Immunofluorescent staining of the brachypod cartilage revealed a deficiency in and an abnormal distribution of the proteoglycans. Although there was no recognizable difference in the immunofluorescent staining for type II collagen between the mutant and wild-type, electron micrographs showed the presence of thick fibrils in the matrix. Other atypical structures in the brachypod cartilage included pleomorphic nuclei, reduced intracellular glycogen granules and profuse intercellular contacts. It is proposed that with the use of this in vitro system which supports the autonomous development of the individual limb elements, experiments concerning the pathogenesis of skeletal mutations such as brachypod should be more feasible. PMID- 1609960 TI - The migration and distribution of somite cells after labelling with the carbocyanine dye, Dil: the relationship of this distribution to segmentation in the vertebrate body. AB - The cells of individual somites in 2-day-old chick embryos were marked by injecting a fluorescent dye into the somitocoele. This procedure permanently marked the cells and allowed their subsequent development and distribution to be followed. The cells were found to remain in close association with each other within limited boundaries and did not mix to any great extent with similar cells from adjacent somites. Fluorescent cells from single somites were found in the intervertebral disc, connective tissue surrounding two adjacent neural arches, all the tissues between the neural arches, the dermatome, and the associated myotome. No fluorescent cells were found in the notochord or in any nervous tissue apart from accompanying connective tissue. Surprisingly, the vertebral bodies and neural arches did not contain any fluorescent cells apart from those in the connective tissue surrounding them, but this absence of fluorescent cells was thought to be due to the dilution of the fluorescence following cell proliferation. These results provide further experimental support for the theory of resegmentation in vertebral formation, and also provide evidence of a compartmental method of development along the rostrocaudal axis in vertebrates, similar to that already discovered in insects. On the basis of cell lineage criteria, the sclerotome might be considered as a developmental compartment. PMID- 1609961 TI - Spinal neurons projecting to anterior or posterior cerebellum in the pigeon. AB - Spinal afferent fibers have been shown to project both to lobules III-VI and lobule IX of the cerebellum in the pigeon. In the present investigation the cells of origin of these projections and the course of the axons at spinal levels have been studied by the retrograde transport of fluorescent dyes injected into both parts of the cerebellum. In the upper cervical segments labeled neurons are located predominantly in the ventral horn; the axons cross to the contralateral side. In the cervical enlargement labeled neurons concentrate in the avian cervical Clarke's column (ClC) and in cervical "spinal border cells" (SBC). The axons of ClC neurons project ipsilaterally into the dorsolateral funiculus and SBC project ipsilaterally into the ventrolateral funiculus. In caudal cervical and in thoracic segments dorsal horn neurons (laminae IV/V) are at the origin of an ipsilateral spinocerebellar pathway in the dorsalmost part of the lateral funiculus. In the lumbosacral enlargement there are mainly three spinocerebellar cell groups all of which project contralaterally into the ventral funiculus: ClC, SBC and paragriseal cells. During its ascent this pathway shifts to the lateral funiculus. In addition there is a crossed pathway from ventral horn cells throughout the spinal cord. Whereas approximately equal numbers of dorsal horn cells project to lobules III-VI and to lobule IX, the number of ClC neurons is strongly reduced after lobule IX injections and SBC neurons are nearly absent. Altogether lobule IX has a substantial input from dorsal horn neurons (cutaneous mechanoreception) whereas that to lobules III-VI is dominated by ClC and SBC (proprioreception). PMID- 1609962 TI - Developmental staging in a marsupial Dasyurus hallucatus. AB - In a marsupial, Dasyurus hallucatus, pouch-young of various ages from newborn to 55 days were embedded in wax and serially sectioned. On the basis of the relative development of external and internal characteristics, they were placed in the Carnegie staging system developed by Streeter and elaborated by O'Rahilly and associates. Birth occurred at stage 15, and the end of embryogenesis (stage 23) was reached about day 33. Whereas stage 23 is characterised in all eutherians by the closure of the secondary palate, this occurs before stage 15 in D. hallucatus. Since most other characters of the newborn are at a stage 15 level of development, there has been a relative acceleration of development of the secondary palate (and forelimb) in D. hallucatus that allows it to suckle and breathe at the same time. Between D. hallucatus and eutherians, there is general agreement in the sequence of development and in the relative degree of most structures at each stage. Further marsupials should be examined to see if the minor differences noted are peculiar to D. hallucatus or apply to marsupials generally. PMID- 1609963 TI - Parvalbumin immunoreactive neurons and fibres in the teleost cerebellum. AB - The distribution of parvalbumin- (PV) immunopositive cell bodies and fibres in the cerebellum of two species of freshwater teleosts (Salmo gairdneri and Barbus meridonalis) was studied using a monoclonal antibody and the avidin-biotin immunoperoxidase technique. A clear laminated pattern of PV immunoreactivity was observed. After PV-immunostaining, Purkinje cells were strongly labelled in their cell bodies, the initial segments of the axons and the dendritic trees. In the molecular layer, only the dendritic branches of the Purkinje cells were PV positive. In the granule cell layer, extensive axonal plexuses and scattered cell bodies were observed. Most of the immunopositive perikarya were unequivocally identified as displaced Purkinje cells, whereas a reduced number of smaller neurons with unstained dendrites was also found. Eurydendroid cells, the efferent neurons of the teleost cerebellum, were negative; however, they were impinged upon by numerous PV-positive boutons, corresponding to terminals of Purkinje cell axons. Parallel fibres and climbing fibres, as well as stellate cells and granule cells were negative. Basket cells (or deep stellate cells) whose existence in the teleost cerebellum is discussed, were also not observed. The immunoreactivity distribution pattern for PV in the teleost cerebellum differs from previous observations on the localization of this protein in the cerebellum of amniotes. PMID- 1609966 TI - 3-D observation of actin filaments during cardiac myofibrinogenesis in chick embryo using a confocal laser scanning microscope. AB - Using a confocal laser scanning microscope (CLSM), we observed subcellular three dimensional (3-D) arrangements of actin filaments stained with fluorescein labeled phalloidin during myofibrinogenesis of chick embryonic heart (7- to 13 somite stages). Serial optical tomograms were obtained from whole-mounted heart tubes and reconstructed into stereoscopic images. Development of myofibrils in myocardial differentiation considerably differed in inner and outer myocardial cell layers. In the outer layer, initial myofibrils appeared along cell membranes at the 8-somite stage. They increased rapidly and constituted network structures with spatial extension over cell-cell junctions. In the inner layer, myofibrils appeared at the bottom, facing the cardiac jelly, at the 10-somite stage, and, when the straight heart tube began to bend, they were already aligned circumferentially in the direction of the heart tube. Double staining of fluorescein-phalloidin and DiI [1,1'-dioctadecyl-3,3,3',3'-tetramethylindo carbocyanine perchlorate; DiI-C18-(3)] of the looped heart revealed that while myocytes in the outer layer were round, those of the inner layer were spindle shaped, and their long axes coincided with the circumferential direction. These results suggest that the circumferentially arranged myofibrils at the bottom of the inner layer may play an important role in the looping of the heart tube. PMID- 1609964 TI - Histochemical distribution of zinc in the brain of the rainbow trout, Oncorhynchos myciss. I. The telencephalon. AB - The present paper which describes the distribution of zinc in the telencephalon of the rainbow trout, Oncorhynchos myciss, is the first report on the distribution of a heavy metal in the fish brain. Zinc was demonstrated histochemically by silver enhancement using the Neo-Timm method. The staining was mainly confined to the neuropil, but both moderately and intensely stained nerve cell bodies were of common occurrence. Stained fibers were never observed. The staining revealed a specific distribution pattern which could easily be correlated with the telencephalic nuclei defined on the basis of cytoarchitectural features. However, the telencephalon stained much more weakly than the rest of the brain, in striking contrast to the situation in the reptilian, mammalian, and avian brain. In these classes, high staining intensities are observed almost exclusively in the telencephalon. The staining was essentially restricted to the nuclei of the ventral telencephalic area. In the dorsal telencephalic area, only the medial and central zones and medial part of the posterior zone showed comparable staining intensities. The Neo-Timm staining pattern lends support to the view that the pallio-subpallial boundary is between the medial and dorsal zones of the dorsal telencephalic area. The distribution of zinc has been compared with the terminal field of afferent projections, known from experimental mapping, and also with the distribution of substance P and vasoactive intestinal peptide. Finally, the possible functional implications of zinc in synaptic vesicles are considered. PMID- 1609965 TI - The masking effect of sialic acid on Con A, PNA and SBA ectoderm binding sites during neurulation in the bantam chick embryo. AB - The masking effect of sialic acid on cell surface carbohydrates localized on the ectoderm in stage 6-11 bantam embryos was examined using fluorescein isothiocyanate-labeled Con A, PNA, SBA, LFA, and LPA before and after neuraminidase treatment. The results showed selective lectin binding on both the neuroectoderm and the surface ectoderm. In general, these lectin-binding sites increased or were at least expressed on neuroectoderm during neurulation. On the apical surfaces of the developing neuroectoderm, masked Con A-binding sites were evident from the earliest stage and rapidly increased. These sites coexisted with unmasked binding sites which gradually increased. Masked PNA sites were rarely observed but became abundant in later stages, even though coexistent unmasked sites also rapidly increased. Masked SBA sites were poorly observable in the early stage and gradually increased thereafter, whereas unmasked sites were expressed at later stages. On the basal surfaces masked Con A sites were evident in the early stages but gradually decreased in later stages, whereas unmasked sites were relatively abundant and increased thereafter. Masked PNA sites were evident and increased very rapidly, whereas unmasked sites became observable up to the latest stage. Masked SBA sites were minimal in all three stages, and unmasked sites expressed themselves slightly at later stages. The change in composition of carbohydrates on the developing neuroectoderm was obviously different from that on the developing surface ectoderm. On the contact surface of the neural ridge, the number of masked sites of penultimate sugars was large at Con A sites, slight at PNA and SBA sites, which coexisted with unmasked sugar chain terminals in the areas where Con A sites were moderate and where PNA and SBA sites were poor. Finally, the role of masking on binding sites for Con A, PNA and SBA during neural tube closure is discussed, and the observation that the apparent masking effect on three lectin binding sites did not correspond to the content of sialic acid detected by LFA and LPA is a subject for further study. PMID- 1609967 TI - Immunolocalization of enamel proteins during amelogenesis in the cat. AB - Amelogenesis in the cat has been suggested to closely resemble enamel formation in human teeth. In order to further characterize the sequence of events leading to enamel formation in the cat, the expression and distribution of enamel proteins throughout amelogenesis were examined by postembedding immunocytochemistry using an antibody to mouse amelogenins and the high resolution protein A-gold technique. Enamel proteins were first immunodetected in ameloblasts and in the extracellular matrix during the presecretory stage. Secretory stage ameloblasts showed the most intense cellular reactivity. In these cells, protein synthetic organelles, secretory granules, and large lysosome-like structures were all intensely labeled. Extracellularly, numerous gold particles were observed over enamel and over patches of material found at the baso-lateral surfaces of these ameloblasts. During the early maturation stage, the protein synthetic organelles and secretory granules of ameloblasts still showed some immunoreactivity, although the most conspicuous labeling at this later stage was found over enamel and over material present among the extensive apical membrane infoldings of ruffle-ended ameloblasts. Qualitative analysis of lysosome-like elements in ameloblasts suggested that their frequency and immunoreactivity in the maturation stage were relatively lower than in the secretory stage, where some groups of cells often showed numerous large labeled structures. The enamel matrix was intensely labeled at all stages; however, cervical-occlusal and surface-depth gradients were readily apparent by conventional staining and by quantitative analysis of immunolabeling in the late secretory and early maturation stages. These data suggest that the cellular and extracellular distribution of enamel proteins in the cat is generally similar to that reported in other species, although some particularities were observed, perhaps reflecting variation in the timing of developmental parameters. PMID- 1609968 TI - The surface lamina of the articular cartilage of human zygapophyseal joints. AB - Literature referring to the conflicting results of investigations into the possible existence and composition of the lamina splendens is reviewed. Two hundred micrometer thick histological sections from 80 human cadaveric lower lumbar zygapophyseal joint articular cartilages were examined by ordinary light and darkfield microscopy. The findings illustrate what appears to be an acellular surface lamina on the opposing cartilaginous surfaces. No speculation is made regarding the possible physiological significance of the lamina based on this anatomical study. PMID- 1609969 TI - Development of cartilage and bone tissues of the anterior part of the mandible in cichlid fish: a light and TEM study. AB - The present paper presents ultrastructural details of chondrogenesis of Meckel's cartilage and of ossification of its associated peri- and parachondral bones in a teleost fish, the cichlid Hemichromis bimaculatus. We have distinguished four stages during chondrogenesis, each of which is characterized by specific cellular and matrix features: blastema, primordium, differentiated cartilage and cartilage surrounded by perichondral bone. The blastema is characterized by prechondroblasts and the lack of cartilage matrix; the primordium by chondroblasts and the onset of secretion of matrix of fibrillar and granular nature; differentiated cartilage is characterized by chondrocytes and larger amounts of typical hyaline cartilage matrix. Once perichondral bone is laid down, the chondrocytes show degenerative features but not true hypertrophy. Differentiation of the cartilage cells is attended with cytoplasmic changes indicative of an increasing secretory activity. There is a regional calcification of the cartilage matrix by fusion of calcospherites. Chondrogenesis of the symphyseal area is continuous with that of the rami but starts slightly later. Formation of perichondral bone at the cartilage surface is attended with the deposition of a transitional zone apparently containing a mixture of the two matrices. The role of the perichondral cells is discussed and it is proposed that they may contribute to the formation of the two matrices. The transitional zone may then result either from a diffusion process or from the simultaneous deposition of elements of the two matrices. Growth of the cartilage is argued to be largely the result of matrix secretion, except in the symphyseal area where appositional growth probably occurs until the region is completely covered by perichondral bone. This paper provides a basis for further studies on the developmental interactions between cartilage, bone and teeth during mandibular development in cichlids. PMID- 1609970 TI - Muscle atrophy continues after early cast removal following tendon repair. AB - We studied soleus (SOL), plantaris (PLN), and gastrocnemius (GST) muscles to determine whether early cast removal minimizes muscle atrophy or permits recovery from atrophy after tendon repair. After right tendocalcaneus (Achilles tendon) was transected and repaired, rabbit right hindlimbs were immobilized with the ankle plantar flexed and the knee flexed to 90 degrees. Rabbits were maintained in the cast and sacrificed at 5, 15, or 21 days postoperatively or the cast was removed on day 5 and the animals sacrificed at day 15 or 21. SOL, PLN, and GST muscles of both limbs were removed and weighed, and then histochemical analyses were performed on SOL and PLN muscles. Immobilization decreased SOL muscle wet weights, mean fiber cross-sectional area, and percentage of Type I fibers and increased the percentage of Type IIc fibers. Ten days after cast removal (i.e., postoperative day 15), SOL muscle atrophy and fiber composition did not differ significantly from continuously immobilized controls. However, 16 days after cast removal (i.e., postoperative day 21), SOL muscle fiber cross-sectional area and fiber composition were near normal, differing significantly from continuously casted controls. At each of the time intervals studied, PLN (containing many glycolytic fibers) did not atrophy as much as SOL (containing mainly oxidative fibers). Our results indicate that 1) early cast removal prevents atrophy of PLN glycolytic fibers, but not oxidative fibers in either PLN or SOL, and 2) early cast removal promotes recovery from atrophy of both oxidative and glycolytic fibers. In spite of the many differences between rabbits and humans, these findings suggest that, although early cast removal may not prevent oxidative muscle fiber atrophy after postoperative immobilization, it may facilitate recovery from atrophy. PMID- 1609971 TI - Protein-gold transport in the endocytic complex of trophotaenial absorptive cells in the embryos of a goodeid teleost. AB - This paper reports adsorptive endocytosis of exogenous proteins by the trophotaenial absorptive cells (TACs) in the viviparous goodeid teleost, Ameca splendens. In vitro incubations were performed with gold conjugated to bovine serum albumin (Au-BSA), human transferrin (Au-HTf), fetuin (Au-Fet), and asialofetuin (Au-ASFet). Localization of gold label on the TAC surface was nearly exclusive to patches of an amorphous coat associated with part of the intermicrovillous plasma membrane. On addition of excess BSA, HTf, Fet, or ASFet to incubation media containing, respectively, Au-BSA, Au-HTf, Au-Fet, or Au ASFet, the density of gold particles adsorbed on the TAC surface decreased drastically. Moreover, attachment of the four protein-gold complexes to the same plasma membrane sites was suggested by reciprocal inhibitory effects. Further proteins such as hemoglobin, myoglobin, and cytochrome c were as well potent inhibitors of Au-BSA and Au-HTf binding and uptake. Binding of TACs of native BSA or HTf was visualized by immunogold labeling. The interactions between proteins and binding sites required both the presence of Ca2+ and appropriate pH greater than 6.6. Analyses of the concentration-dependent BSA and HTf binding curves, plotted from morphometric data, resulted in apparent dissociation constants, Kds, of approximately 5 x 10(-7) M and 4 x 10(-7) M, respectively. Following binding at the TAC surface and internalization via clathrin-coated pits and vesicles the several ligands were routed along the lysosomal pathway with transit through the endosomal compartment. Prolonged incubation periods led to massive intracellular accumulation of tracer proteins. The effects of NH4Cl (10 mM) treatment on TACs included enormous cytoplasmic vacuolation, a reversible loss of protein binding sites on the plasma membrane, and a block in the transport of protein-gold complexes to lysosomes. PMID- 1609972 TI - Examination by scanning electron microscopy of oviductal epithelium of the prolific Chinese Meishan pig at follicular and luteal phases. AB - The luminal surfaces of epithelial cells in the fimbriae, ampulla, isthmus, and utero-tubal junction of the oviducts of the prolific Chinese Meishan pig at follicular and luteal phases of the estrous cycle were examined by scanning electron microscopy. Marked cyclic changes were observed on the surfaces of cells in the fimbriae and ampulla, but little change was found in the isthmus and at the utero-tubal junction. The cells of the fimbrial epithelium in the follicular phase were densely ciliated, and the cilia partially concealed the bulbous processes of the secretory cells. In the luteal phase, the secretory cells predominated in the epithelium, and most of the ciliated cells were hidden by the processes of the secretory cells. The ampullar epithelium showed similar changes, but to a lesser extent. In the isthmus and at the utero-tubal junction, the secretory cells had many microvilli on their bulbous processes at the follicular phase, but they were flat and the microvilli were fewer in number and shorter in length during the luteal phase. Conspicuous solitary cilia protruded from the surfaces of secretory cells in the fimbriae and ampulla during the luteal phase. These results demonstrate that there are regional variations in the cyclic changes associated with the oviductal epithelial cells of the Chinese Meishan pig. PMID- 1609973 TI - Macrophage development: IV. Effects of blood factors on macrophages from prenatal rat lung cultures. AB - Effects of colony-stimulating factors M-CSF, GM-CSF, G-CSF, and IL-3 were assessed on cells of macrophage lineage present in organ cultured 14-day prenatal rat lungs. Treatment groups were compared between one another and against control lungs grown on standard medium containing 40% fetal bovine serum without added factors, where a monoculture of macrophages rapidly develops from precursors present at explantation, leading to appearance of a large mature population on the pleural surface outside the lungs. Studies were carried out in living cultures and by light and electron microscopy using peroxidase-coupled isolectin B4 of Griffonia simplicifolia to identify macrophages and their precursors. In the first experiment, 14-day prenatal lung explants (14 + 0 days) containing macrophage precursors but not matured cells were exposed to individual CSFs for 7 days in an attempt to determine whether precursors are committed irrevocably to the macrophage line or can be altered by exposure to factors promoting significant granulocyte development. In succeeding experiments, 4- and 7-day-old cultures (14 + 4, 14 + 7 days) containing matured macrophages were targeted to see whether macrophage survival can be extended beyond expectations in controls and whether mitotic activity is stimulated. Recombinant CSFs were used at dosage levels known to promote colony formation in vitro (200-1,000 CFU/ml). Cultures exposed from prenatal day 14 to M-, GM-, G-CSF, or IL-3 yielded a monoculture of macrophages without exception. Populations developed in the presence of M- or GM CSF were much larger than in controls or cultures grown with the other blood factors. GM-CSF-exposed cultures produced by far the largest macrophages, among them many multinucleate giant cells. Macrophages developed in the presence of G CSF were also significantly larger than controls. Growth of the mature macrophage population was greatly stimulated by exposure to M-CSF or GM-CSF but not by IL-3 or G-CSF. Mitotic figures were noted in the coronas of emerged cells surrounding stimulated cultures, compared to none in the controls. Ultrastructurally, macrophages stimulated by M-CSF retained a mature appearance like macrophages in control, IL-3, and G-CSF treatment groups, whereas many in the GM-CSF group became less differentiated. As to long-term survival, a single 14-day explant was grown for 8 days on standard medium (the equivalent date for birth), then placed in a soft agar medium containing M-CSF.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1609974 TI - Anatomical studies of the coronary system in elasmobranchs: II. Coronary arteries in hexanchoid, squaloid, and carcharhinoid sharks. AB - Coronary artery anatomy was studied in 16 shark species belonging to 9 families of the orders Hexanchiformes, Squaliformes, and Carcharhiniformes. The study included 101 specimens and used an injection-corrosion technique that obtained internal casts of the main trunks and coronary arterial branches. The results showed 2 main patterns of coronary arterial arrangement: the dorsoventral coronary trunk pattern, shared by lamnoid and advanced carcharhinoid sharks, and the lateral coronary trunk pattern, shown by hexanchoid and squaloid sharks. Scyliorhinus and Galeus had intermediate arrangements of their vessels. PMID- 1609975 TI - Endothelial cells and hematopoiesis: a light microscopic study of fetal, normal, and pathologic human bone marrow in plastic-embedded sections. AB - The origin and morphological identity of hematopoietic progenitor cells, as well as their precursor, the pleuripotential hematopoietic stem cell (HSC), has not been established. Our studies of 2 microns sectioned undecalcified plastic embedded bone marrow (BM) from healthy human fetuses; normal adults; patients with acute myeloblastic leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic granulocytic leukemia (CGL) in various stages (chronic, accelerated, acute blastic phase, and after autografting); and patients recovering from therapy-induced marrow hypoplasia suggest that proliferative hematopoietic zones exist near the endosteum (endosteal marrow) and the vascular endothelium (capillary and sinus-lining endothelium) and a maturational zone distal to these regions. In some of these areas, morphologically recognizable hematopoietic cells were seen and interpreted as emerging and maturing in a sequential progression, suggesting an origin from the endosteal or endothelial progenitors. In other loci, early hematopoietic cells were seen in close contact with the endosteal or vascular endothelial (VE) cells. This latter relationship suggested that these areas of cellular contact were important and represented sites of cell to cell interaction that may be associated with the liberation of growth factors by endosteal and endothelial cells and their action on hematopoietic progenitor cells. Following treatment-induced hypoplasia, the endosteal and VE cells were seen to modulate, transform, and migrate into the surrounding empty and edematous marrow space as fibroblasts. Later, as hemopoietic regeneration began, clusters of regenerating hematopoietic cells were seen adjacent to bone trabecule (BT) and near the vascular endothelium. We postulate that endosteal and VE cells are the equivalent of embryonal-stage, undifferentiated mesenchyme and, under the appropriate regulatory influence, are capable of modulation and transformation (differentiation) into stromal (fibroblast-like) cells and precursors of hematopoietic cells in normal (physiologic) and stressed (pathologic) conditions. Recently, human endothelial cells have been shown to express a large number of cell surface antigens in common with hematopoietic (myeloid and lymphoid) cells. It is also possible that, in some situations, the VE cells act to establish a microenvironment and liberate growth factor(s), enabling pleuripotential and progenitor cell differentiation into mature hematopoietic cells adjacent to the vascular endothelium. Indeed, vascular endothelium has been shown to elaborate growth factors that participate in normal hematopoiesis. PMID- 1609976 TI - Development of the human sphenomandibular ligament. AB - The development and arrangement of the sphenomandibular ligament of 60 human embryos and fetuses were studied. Meckel's cartilage appeared as a single, continuous fibrous structure lying between the mandibular lingula and the malleus of the middle ear in fetuses of 210 mm crown-rump length (22 weeks of age) and over. This structure constitutes the malleolomandibular ligament, and two clearly differentiated portions bound by the tympanosquamosal fissure could be seen: a juxtaarticular portion, inserted on the posterior edge of the interpterygoid aponeurosis, and a tympanic portion, onto which the disc of the temporomandibular joint inserted. Some of the authors consider that if tension is applied to the sphenomandibular ligament this may injure the middle ear. The anatomical arrangement of the sphenomandibular ligament could explain these injuries. PMID- 1609977 TI - Ultrastructural characteristics of glomus cells in the external carotid artery during larval development and metamorphosis in bullfrogs, Rana catesbeiana. AB - Electron microscopic observations of the external carotid artery in the larvae of the bullfrog, Rana catesbeiana, showed that glomus cells are present in the subendothelial stroma of the septum between the expanded region of the external carotid artery and the carotid arch. There were some differences in the ultrastructure of the glomus cells at each stage of larval development. At the early stages (stages I, III, V, X), most glomus cells were isolated and free from the covering of a supporting cell. The cytoplasm of the glomus cells contained fewer dense-cored vesicles. No synaptic junctions were observed. At the middle stages (stages XV, XX, XXI), some glomus cells showed a tendency to form small clusters. Between adjacent cells in a cluster, gap junctions were often observed. The number of dense-cored vesicles increased remarkably. Intimate apposition of the glomus and smooth muscle cells (g-s connection) was also observed. Nerve terminals containing clear vesicles were observed in synaptic contact with glomus cells at this phase. At the metamorphic climax (stages XXII-XXV), in addition to g-s connections, the glomus cells made intimate apposition to the cells around the glomus cells. The afferent synapses described in other amphibians were not encountered in this study. These findings suggest that the glomus cells at the early stages of development are nonfunctional, the vascular regulation via the g s connection starts at the middle stages, and the chemoreception starts after metamorphosis. PMID- 1609978 TI - Insulin improves survival but does not maintain function of cultured chick wing bud apical ectodermal ridge. AB - Previously we demonstrated that high levels of insulin (5 micrograms/ml) permit the survival of isolated chick apical ectodermal ridge in culture (Boutin and Fallon, Dev. Biol., 104:111-116, 1984). Here we address whether lower levels of insulin or insulin-like growth factors (IGFs) can also improve the survival of cultured apical ectodermal ridge and whether ridge function is maintained along with ridge survival. Neither IGF I nor IGF II (100 ng/ml) decreased ridge cell death; however, cell death was significantly decreased with 50 ng/ml insulin. No further improvement was obtained in the presence of both IGF I and insulin. These data suggest that insulin improved the survival of the isolated apical ectodermal ridge by binding its own receptor. To test for the maintenance of function, stage 20 ridges were cultured for 0, 6, 12, 18, or 24 hr with or without insulin (5 micrograms/ml or 5 ng/ml) and used to make recombinant limbs. Isolated ridges cultured for 12 hr or more produced fewer outgrowths and these were rarely distally complete. The medium in which the ridges had been cultured did not influence ridge activity, despite the major differences in cell survival. Recombinants made with ridges cultured with limb mesoderm for 18 hr did not yield outgrowths as often as those with freshly isolated ridges, but most of the limbs that did form were distally complete. These results suggest that the decline in function of cultured, isolated apical ectodermal ridge was not due merely to ridge cell death but rather, at least in part, to its separation from limb mesoderm. PMID- 1609979 TI - Localization of 5-hydroxytryptamine-like immunoreactive cells and nerve fibers in the rat female reproductive system. AB - The presence of 5-hydroxytryptamine (5-HT)-like immunoreactivity (IR) was studied in the rat female reproductive system using polyclonal antibodies directed against 5-HT. Moreover, 5-HT levels in the ovary, oviduct, uterus, and cervix were measured by high-pressure liquid chromatography with electrochemical detection. The highest 5-HT concentrations were found in the oviduct, followed in descending order by the cervix, the ovary, and the uterus. Most 5-HT-like IR was observed in the cytoplasm of mast cells. These cells were found in the connective tissue around the fimbria, in the oviduct, in the uterus, and in the ovary. Mast cells are clustered in the proximity of the parenchymal blood vessels. Moreover, a few 5-HT-like nerve fibers were found distributed mainly perivascularily in the uterine cervix and in the uterine horns as well as in the oviduct. IR nerve fibers were rarely seen within the ovary. The present data provide direct evidence that 5-HT in the female reproductive system not only is associated with mast cells but is located in nerve fibre-like structures as well. The functional significance of this probable 5-HT-ergic innervation of the female reproductive tract discovered in the present study should be clarified in future investigations. PMID- 1609980 TI - Radiographic analysis of the arteries of human lumbar lymph nodes. AB - Twenty-seven cadavers (12 male, 15 female aged 28 to 94 years, average 75 years) were dissected to analyze the arterial supply of the lumbar lymph nodes with angiography and an image processor-analyzer. The lymph nodes on the left side of the abdominal aorta fused to form several elongated nodes. The lymph nodes on the right side remained separated. A few lymph nodes aggregated below the bifurcation of the abdominal aorta. They received a few branches directly from the abdominal aorta or from the renal, gonadal and/or iliac arteries, which anastomosed with each other to form an arterial arc. This anastomosis gave small paired twigs to the parenchyma continuously. In the case of well developed lymph nodes dorsal to the inferior vena cava, a vessel from the lower abdominal aorta passed upward to supply them. The diameter of these vessels in the angiogram was 0.09-0.27 mm, measured with the image processor-analyzer. These results show that the lumbar lymph nodes do not receive a single artery through the hilus, but through several branches, whose anastomoses form a collateral system associated with the abdominal aorta. PMID- 1609981 TI - Concerning the ethics and accuracy of scientific citations. PMID- 1609982 TI - Central temperature changes are poorly perceived during epidural anesthesia. AB - Hypothermia and shivering are common during epidural anesthesia for cesarean delivery but are not always accompanied by a sensation of coldness. To test the hypothesis that central temperature changes are not perceived during epidural anesthesia, we measured central and skin temperatures and thermal perception in 30 patients undergoing cesarean delivery with epidural anesthesia. Central temperature decreased 1.0 +/- 0.6 degrees C from control values during anesthesia and surgery, but thermal perception scores did not reflect central temperatures (P = 0.56) or changes in central temperature (P = 0.63). A feeling of warmth was significantly correlated with increased mean skin temperature (P = 0.02) and increased upper body skin temperature (P = 0.03). We conclude that central temperature is poorly perceived and is less important than skin temperature in determining thermal perception during high levels of epidural anesthesia. PMID- 1609983 TI - Which vasopressor should be used to treat hypotension during magnesium sulfate infusion and epidural anesthesia? AB - Ephedrine restores and/or protects uterine blood flow and fetal well-being in laboratory animals. In contrast, alpha 1-adrenergic agonists worsen uterine blood flow and fetal condition. We previously demonstrated that magnesium sulfate (MgSO4) attenuates the detrimental effects of phenylephrine on uterine vascular resistance in gravid ewes. Therefore, we performed this study to determine whether ephedrine or phenylephrine better restores and protects uterine blood flow and fetal oxygenation during epidural anesthesia-induced hypotension in hypermagnesemic gravid ewes. Twelve chronically instrumented gravid ewes were each used for three experiments: 1) ephedrine, 2) phenylephrine, and 3) normal saline (NS)-control. For each experiment the protocol was as follows: 1) at time zero, intravenous infusion of MgSO4 was begun; 2) at 150 min a thoracic level of epidural anesthesia was achieved with 2% lidocaine; and 3) at 165 min, an intravenous infusion of ephedrine, phenylephrine, or NS was begun and continued through 195 min. Epidural anesthesia uniformly decreased maternal mean arterial blood pressure (MAP), heart rate, cardiac output, uterine blood flow, and fetal PO2 in each of the three groups. Both ephedrine and phenylephrine restored maternal MAP to baseline, as expected from the experimental design. Ephedrine significantly increased cardiac output and uterine blood flow when compared with NS-control, but phenylephrine did not. Phenylephrine significantly increased uterine vascular resistance when compared with NS-control, but ephedrine did not. As a result, fetal pH and PO2 were significantly greater during ephedrine infusion than during infusion of NS-control. Fetal pH was stable during ephedrine infusion, but it continued to decrease during phenylephrine infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609984 TI - Enflurane-induced release of an excitatory amino acid, glutamate, from mouse brain synaptosomes. AB - To clarify the mechanisms of enflurane-induced convulsions, we examined the effects of enflurane, halothane, and diethyl ether on the release of an excitatory neurotransmitter, glutamate, from isolated pinched-off nerve terminals (synaptosomes) of the mouse cerebral cortex. At concentrations corresponding to those used clinically (0.75 and 1.25 mM), enflurane released more glutamate than did halothane. Diethyl ether (10 and 58 mM) had no effect on glutamate release. Enflurane (0.75-15 mM) increased glutamate and aspartate release in a dose dependent manner but had little effect on the release of the inhibitory neurotransmitters glycine and gamma-aminobutyric acid or on the release of glutamine. A glutamate uptake inhibitor, kainic acid (1 mM), did not affect enflurane-induced glutamate release. Replacement of the medium's Ca2+ by Co2+, or exposure to cold (about 2 degrees C), suppressed the enflurane-induced glutamate release. Depolarization caused by 40 mM K+ increased the basal level of glutamate released, and enflurane-induced glutamate release was lower after depolarization. Enflurane had no effect in synaptosomes prepared from the cerebellum, diencephalon and pons, or medulla oblongata. Thus, enflurane increased Ca(2+)- and temperature-dependent glutamate release, especially from synaptosomes of the cerebral cortex. These data provide a pathophysiologic explanation for enflurane induced convulsions. PMID- 1609985 TI - The effects of volatile anesthetics on calcium regulation by malignant hyperthermia-susceptible sarcoplasmic reticulum. AB - To clarify the mechanism by which volatile anesthetics initiate malignant hyperthermia (MH), we examined the effect of halothane, isoflurane, and enflurane on Ca2+ uptake and release by sarcoplasmic reticulum vesicles isolated from MH susceptible (MHS) and normal pig muscle. Clinical concentrations of these anesthetics (0.1-0.5 mM) stimulated sarcoplasmic reticulum ATP-dependent Ca2+ uptake (maximal at approximately 4 mM), whereas 10-20 times the clinical anesthetic concentration inhibited Ca2+ uptake. There was no significant difference between MHS and normal sarcoplasmic reticulum in any aspect of Ca2+ uptake. Ca2+ release from 45Ca(2+)-filled sarcoplasmic reticulum vesicles in a 10(-8) M Ca(2+)-containing medium (pH 7.0) was significantly stimulated at clinical concentrations of all three volatile anesthetics (anesthetic concentration for the 50% stimulation of Ca2+ release = 0.096-0.22 mM); however, the rate constant for Ca2+ release from MHS sarcoplasmic reticulum was in all cases significantly greater than that from normal sarcoplasmic reticulum. Furthermore, 0.5 mM halothane had no effect on Ca2+ release from normal sarcoplasmic reticulum at pH values less than 6.8, although it could still significantly stimulate Ca2+ release from MHS sarcoplasmic reticulum even at pH 6.4; similar results were obtained for isoflurane and enflurane. These studies thus demonstrate that the interaction of volatile anesthetics with the sarcoplasmic reticulum Ca(2+)-release channel is altered in MHS porcine muscle such that the channel may be activated even at a Ca2+ concentration or pH that would be expected to maintain the channel in the closed state. PMID- 1609986 TI - Electrophysiologic and arrhythmogenic effects of bupivacaine. A study with high resolution ventricular epicardial mapping in rabbit hearts. AB - It has been shown that administration of toxic doses of bupivacaine may induce ventricular dysrhythmias. However, the mechanism of these dysrhythmias is still unknown. The present study was designed to test the hypothesis that bupivacaine facilitates the occurrence of reentrant ventricular dysrhythmias. High-resolution ventricular epicardial mapping was used to study the effects of 0.2, 0.5, 1.0, and 5.0 micrograms/ml bupivacaine in 11 Langendorff-perfused rabbit hearts. Five hearts were kept intact (intact heart). In six other hearts, a thin layer of epicardium was obtained by an endocardial cryotechnique (frozen heart). Bupivacaine induced ventricular dysrhythmias in 3 of 5 intact hearts at 5.0 micrograms/ml. In 3 of 6 frozen hearts, 0.2 micrograms/ml bupivacaine facilitated the induction of ventricular tachycardia by programmed electrical stimulation. Epicardial mapping showed that all tachycardias were based on reentry of the impulse around an arc of functional conduction block. Moreover, bupivacaine significantly prolonged the ventricular effective refractory period and slowed longitudinal and transverse conduction velocity in a dose- and use-dependent manner. It is concluded that bupivacaine facilitates induction of reentrant ventricular dysrhythmias in isolated rabbit heart. PMID- 1609987 TI - Severe hypoxia enhances central nervous system and cardiovascular toxicity of bupivacaine in lightly anesthetized pigs. AB - Toxic systemic reactions to bupivacaine usually involve a number of factors, including hypoxia and acidosis. The objective of this study was to test the hypothesis that cardiovascular and central nervous system responses to bupivacaine overdose are proportional to the severity of hypoxia. The central nervous system and cardiovascular toxicity of bupivacaine was examined in three groups of pigs breathing 30%, 15%, or 10% O2, 70% N2O, and He (FIO2 = 0.15 and 0.1 groups). The 18 2-week-old pigs (6 animals per treatment) were paralyzed with pancuronium and their lungs ventilated mechanically. During the intravenous infusion of bupivacaine 2 mg.kg-1.min-1, four readily identified toxic endpoints (seizures, arrhythmias, isoelectric electroencephalogram, asystole) were observed in all animals, with the exception that 1 pig in the FIO2 = 0.3 group and 1 in the FIO2 = 0.15 group had no arrhythmias. Bupivacaine doses producing seizures, isoelectric EEG, and asystole were significantly less in the FIO2 = 0.1 groups as compared to the other groups. Arrhythmias occurred before seizures in all animals in the FIO2 = 0.1 group but in only 1 of 5 and 2 of 5 animals in the FIO2 = 0.15 and 0.3 groups, respectively. There was no significant difference between the arrhythmic dose of bupivacaine in the FIO2 = 0.3 versus 0.1 animals (8.4 +/- 2.4 vs. 4.0 +/- 1.4 mg.kg-1), but the dose was significantly less in the FIO2 = 0.1 animals than in the FIO2 = 0.15 animals (12.5 +/- 5.6 mg.kg-1). Arterial pH was stable in all three groups during bupivacaine infusion.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609988 TI - Detection and hemodynamic consequences of venous air embolism. Does nitrous oxide make a difference? AB - Volume expansion of intravascular air by nitrous oxide (N2O) may improve the sensitivity of monitors used to detect venous air embolism (VAE) and/or exacerbate hemodynamic changes following VAE. The purpose of this study was to determine if the administration of N2O alters the sensitivity (i.e., threshold of detection) of monitors used to detect VAE or the hemodynamic consequences of VAE. Twenty-one dogs were monitored for VAE with precordial Doppler ultrasound, transesophageal echocardiography (TEE), changes in end-tidal carbon dioxide tension (ETCO2), and changes in pulmonary artery pressure (PAP). Venous air was infused at rates between 0.005 and 0.4 ml.kg-1.min-1 during 1 MAC (total anesthetic level) of isoflurane with and without 50% N2O (group 1, n = 7) or isoflurane with and without 75% N2O (group 2, n = 7). The mean quantity of infused air necessary to elicit a positive response in both the presence and absence of N2O was calculated for each monitor. Positive responses were defined as follows: unmistakable audible change in frequency on Doppler ultrasound, visualization of densities consistent with air bubbles in the right cardiac chambers or outflow tract on TEE, a decrease in ETCO2 greater than or equal to 2 mmHg, and an increase in mean PAP greater than or equal to 3 mmHg. In group 3 (n = 7), venous air was infused at rates between 0.1 and 0.8 ml.kg-1.min-1 during 1 MAC (total anesthetic level) of isoflurane with and without 50% N2O. In group 3, N2O administration was discontinued immediately upon Doppler detection of VAE and air infusion continued until mean arterial pressure (MAP) decreased by 10 mmHg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609989 TI - Elucidation of dose-effect relationships for different opiate effects using alfentanil in the spontaneously ventilating rat. AB - In addition to producing antinociception and mild sedation, opiates diminish spontaneous movement and produce muscle rigidity. Examination of the relationship between different opiate effects may lead to a better understanding of the mechanism and sites of action of opiate anesthesia. Previous studies have compared the dose-effect relationships for morphine and fentanyl between antinociception and loss of righting reflex. However, neither muscle rigidity nor lack of spontaneous movement (as measured by catalepsy) has been fully examined or directly compared with either antinociception or loss of righting reflex. This study, therefore, compared five clinically relevant opiate endpoints (antinociception, muscle rigidity, catalepsy, loss of righting reflex, and respiratory depression) using the mu-selective agonist alfentanil in the spontaneously ventilating rat. Rats were randomized to receive alfentanil (0-500 micrograms/kg) subcutaneously. For muscle rigidity, 59 rats had electromyographic activity measured with percutaneous hindlimb electrodes. After alfentanil injection, electromyographic data were recorded for 60 min. For antinociception and catalepsy, 49 rats were studied for 120 min after alfentanil. Catalepsy was measured from the time the rat's forelimbs were placed on a 10-cm-high bar until either limb was removed. Antinociception was studied by measuring tail-flick response to hot (55 degrees C) water. For righting reflex, 40 rats were studied for 120 min. Alfentanil-induced respiratory depression was assessed in 40 rats with indwelling tail arterial catheters. Alfentanil was administered after baseline arterial blood gas measurements, and then additional samples were obtained for 45 min. For each effect, data were converted into quantal responses and were then transformed to probit-log dose-response curves for analysis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1609990 TI - Postoperative nausea and vomiting. Its etiology, treatment, and prevention. AB - In a recent editorial, Kapur described perioperative nausea and vomiting as "the big 'little problem' following ambulatory surgery."257 Although the actual morbidity associated with nausea is relatively low in health outpatients, it should not be considered an unavoidable part of the perioperative experience. The availability of an emesis basin for every patient in the postanesthesia recovery unit is a reflection of the limited success with the available therapeutic techniques.257 There had been little change in the incidence of postoperative emesis since the introduction of halothane into clinical practice in 1956. However, newer anesthetic drugs (e.g. propofol) appear to have contributed to a recent decline in the incidence of emesis. Factors associated with an increased risk of postoperative emesis include age, gender (menses), obesity, previous history of motion sickness or postoperative vomiting, anxiety, gastroparesis, and type and duration of the surgical procedure (e.g., laparoscopy, strabismus, middle ear procedures). Anesthesiologists have little, if any, control over these surgical factors. However, they do have control over many other factors that influence postoperative emesis (e.g., preanesthetic medication, anesthetic drugs and techniques, and postoperative pain management). Although routine antiemetic prophylaxis is clearly unjustified, patients at high risk for postoperative emesis should receive special considerations with respect to the prophylactic use of antiemetic drugs. Minimally effective doses of antiemetic drugs can be administered to reduce the incidence of sedation and other deleterious side effects. Potent nonopioid analgesics (e.g., ketorolac) can be used to control pain while avoiding some of the opioid-related side effects. Gentle handling in the immediate postoperative period is also essential. If emesis does occur, aggressive intravenous hydration and pain management are important components of the therapeutic regimen, along with antiemetic drugs. If one antiemetic does not appear to be effective, another drug with a different site of action should be considered. With the availability of new antiserotonin drugs, the incidence of recurrent (intractable) emesis could be further decreased. Research into the mechanisms of this common postoperative complication may help in improving the management of emetic sequelae in the future. As suggested in a recent editorial, improvement in antiemetic therapy could have a major impact for surgical patients, particularly after ambulatory surgery. Patients as well as those involved in their postoperative care look forward to a time when the routine offering of an emesis basin after surgery becomes a historical practice. PMID- 1609991 TI - Trust, but verify. The accuracy of references in four anesthesia journals. AB - To determine the accuracy of bibliographic citation in the anesthesia literature, we reviewed all 1988 volumes of ANESTHESIOLOGY, Anesthesia and Analgesia, British Journal of Anaesthesia, and Canadian Journal of Anaesthesia and sequentially numbered all references appearing in that year (n = 22,748). One hundred references from each of the four journals were randomly selected. After citations to nonjournal articles (i.e., books or book chapters) were excluded, the remaining 348 citations were analyzed in detail. Six standard bibliographic elements--authors' names, article title, journal title, volume number, page numbers, and year--were examined in each selected reference. Primary sources were reviewed, unless our institution did not own the source or could not obtain it through interlibrary loan, in which case standard indexes, abstracting services, and computerized databases were consulted. Each element was checked for accuracy, and references were classified as either correct or incorrect. A reference was correct if each element of the citation was identical to its source. Of the examined references, more than half (50.3%) contained an error in at least one element. The elements most likely to be inaccurate were, in descending order, article title, author, page numbers, journal title, volume number, and year. No significant differences (P = 0.283) existed in the error rates of the four journals; the percentage of citations containing at least one error ranged from 44% (Anesthesia and Analgesia) to 56% (British Journal of Anaesthesia). The citation error rate of anesthesia journals is similar to that reported in other specialties, where error rates ranging from 38% to 54% have been documented. PMID- 1609992 TI - A comparison in a lung model of low- and high-flow regulators for transtracheal jet ventilation. AB - There is widespread agreement that transtracheal jet ventilation (TTJV) using a percutaneously inserted intravenous (iv) catheter through the cricothyroid membrane is a simple, quick, relatively safe, and extremely effective treatment for the situation in which neither ventilation nor intubation can be achieved. No study has reported whether a low-flow pressure-reducing regulator (LFR) can provide enough driving pressure and flow under a variety of clinical circumstances for adequate TTJV. We determined, using a high-flow regulator (HFR) as our control, the tidal volume (VT) (measured by integrating a pneumotachograph signal) that a LFR could deliver via a Carden jet injector through 14- and 20-G iv catheters initially at an inspiratory:expiratory ratio (I:E) = 1:1 (unit of time = 1 s) in a mechanical model that had varying lung compliance (Cset, 10-100 ml/cmH2O) and airway diameters (proximal trachea 15.0, 4.5, or 3.0 mm ID and distal mainstem bronchi 9.0 or 4.5 mm ID). The lowest Cset (10 ml/cmH2O) and smallest airway diameter (tracheal diameter = 3.0 mm, bronchial diameter = 9.0 mm) resulted in the lowest VT (220 and 320 ml for the 20- and 14-G iv catheters, respectively, with the LFR), and the highest Cset (100 ml/cmH2O) and largest airway diameter (tracheal diameter = 15 mm, bronchial diameter = 9.0 mm) resulted in the highest VT (780 and 1040 ml for the 20- and 14-G iv catheters, respectively, with the LFR). The VT produced during TTJV was greatly dependent on air entrainment (measured by a second pneumotachograph), with the contribution to total VT ranging from 15 to 74%; the amount of air entrainment was independently confirmed by excellent agreement between measured and calculated alveolar oxygen concentrations. Decreasing Cset (with the largest airway diameter) and decreasing airway diameter (at Cset = 50 ml/cmH2O) over the full range studied resulted in approximately a 45-80% decrease in VT for all iv catheter/regulator combinations. Increasing Cset and narrowing airway diameter over the full range studied resulted in a progressive increase in end-expiratory volume (EEV) for all iv catheter/regulator combinations. The I:E ratio was also varied from 1:3 to 3:1 (unit of time = 1 s) using the 14-G catheter at Cset = 50 ml/cmH2O with both regulators at the extremes of the proximal tracheal diameters (15.0 and 3.0 mm ID), and we found that jet ventilation through a proximal tracheal diameter of 3.0 mm with the HFR at I:E ratios = 1:1 and 3:1, EEV exceeded the capacity of the mechanical lung (4,000 ml).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1609993 TI - Bilateral dilated nonreactive pupils during surgery in a patient with undiagnosed pheochromocytoma. PMID- 1609994 TI - Successful cardiopulmonary resuscitation of two patients in the prone position using reversed precordial compression. PMID- 1609995 TI - Masseter muscle rigidity after rapid-sequence induction of anesthesia. PMID- 1609996 TI - Intraoperative awareness with propofol-oxygen total intravenous anesthesia for microlaryngeal surgery. PMID- 1609997 TI - Fifty percent nitrous oxide does not increase the risk of venous air embolism in neurosurgical patients operated upon in the sitting position. AB - Although nitrous oxide (N2O) should theoretically increase the severity of venous air embolism (VAE), data confirming this hazard in clinical situations are not available. The effect of 50% N2O on the incidence and severity of VAE and on the emergence time from anesthesia was evaluated in 300 neurosurgical patients operated upon while in the sitting position. Of these, 110 patients underwent craniectomy for posterior fossa pathology and 190 patients underwent cervical spine surgery (CSS). Patients were randomized to receive either 50% N2O in oxygen (O2) (N2O group) or O2 (no-N2O group) as part of an isoflurane-fentanyl-based anesthetic. In patients in the N2O group, N2O administration was discontinued immediately upon Doppler-detection of VAE and was reinstituted in not less than 30 min after resolution of the episode. The incidence of Doppler-detected VAE was significantly greater in the craniectomy group than the CSS group (43% vs. 7%, respectively; P less than 0.001). N2O had no effect on the incidence of VAE or the severity of VAE as judged by the magnitude of the reduction in blood pressure during hemodynamically significant episodes of VAE, the volume of gas aspirated from the right atrial catheter during episodes of VAE, or the magnitude of the decrease in end-tidal carbon dioxide tension during episodes of VAE. Hemodynamically significant episodes of VAE (i.e., episodes associated with a reduction in systolic blood pressure of greater than or equal to 15 mmHg) occurred in 17 of the 61 patients experiencing VAE (28%) and was not different between the N2O and no-N2O groups. Similarly, hemodynamically significant episodes of VAE (n = 18) accounted for 15% of all episodes of VAE (n = 118) and was not different between the N2O and no-N2O groups. Emergence time was not significantly different between the N2O and no-N2O groups, with mean times of 2 +/- 6 and 3 +/- 7 min (+/- SD), respectively. Emergence time was significantly longer in the craniectomy group than in the CSS group (5 vs. 1 min, respectively; P less than 0.001). Within the craniectomy group, the incidence of Doppler detected VAE was significantly less in patients with previous surgery at the operative site (21%) compared to patients without previous surgery at the operative site (47%). Postoperatively, no complications could be related to the use of N2O or directly attributed to the occurrence of VAE.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1609998 TI - Factors affecting distribution of catheter-injected local anesthetic. PMID- 1609999 TI - Factors affecting distribution of catheter-injected local anesthetic. PMID- 1610000 TI - An additional concern with respect to patient-controlled analgesia. PMID- 1610001 TI - Anterograde, not retrograde, amnesia after thiopental. PMID- 1610002 TI - Amrinone in patients undergoing cardiac surgery. PMID- 1610003 TI - Spinal nerve root is one of the preferred routes for transfer of drugs to the nerve roots and spinal cord from the epidural space. PMID- 1610004 TI - Coronary steal models. PMID- 1610005 TI - Lingual nerve injury. PMID- 1610006 TI - Perioperative corneal abrasions. PMID- 1610007 TI - Pharmacodynamics of propofol in female patients. AB - Although the clinical properties of propofol have been studied extensively, the pharmacodynamics have not yet been described fully. We studied the propofol concentration-effect relationships for loss of eyelash reflex, loss of consciousness, and hemodynamic changes in 18 female patients, ASA physical status 1, aged 20-49 yr. Propofol was given by computer-controlled infusion. The initial target concentration of 0.5-1 microgram/ml was increased every 12 min by 0.5-1 microgram/ml until the patients lost consciousness. Every 3 min, loss of eyelash reflex and loss of consciousness were tested and an arterial blood sample was taken for analysis of the blood propofol concentration. The concentration response relationships for loss of eyelash reflex and loss of consciousness were defined by fitting a sigmoid Emax function (where Emax = the maximum effect that can be reached; i.e., 100% of the patients showing loss of eyelash reflex or loss of consciousness) to the response/no response data versus the propofol concentration, using nonlinear regression. The effect of propofol on hemodynamic parameters was analyzed by linear regression. The propofol concentrations at which 50% and 90% of the patients showed loss of eyelash reflex were 2.07 and 2.78 micrograms/ml, respectively. The corresponding values for loss of consciousness were 3.40 and 4.34 micrograms/ml. The systolic and diastolic blood pressure decreased with increasing blood propofol concentration. The correlation coefficients for the decrease in systolic and diastolic blood pressure versus the blood propofol concentration were r2 = -0.663 and r2 = -0.243, but heart rate did not change. In conclusion, propofol concentrations inducing loss of eyelash reflex are less than those inducing loss of consciousness. PMID- 1610008 TI - Errors in thermodilution cardiac output measurements caused by rapid pulmonary artery temperature decreases after cardiopulmonary bypass. AB - When systemic cooling and rewarming are performed during cardiopulmonary bypass (CPB), the pulmonary artery temperature typically decreases after CPB. This decrease may be rapid enough to cause substantial underestimation of cardiac output (CO) measured by thermodilution, due to changing baseline temperature during the thermodilution measurement. In 16 patients undergoing CPB for coronary artery grafts, digital recording of pulmonary artery temperature was done during room-temperature thermodilution CO (TDCO) injections. TDCO were computed with and without correction for baseline temperature decrease. Prior to CPB, the temperature change was -0.013 degrees C/min, producing no significant effect on CO measurements; the coefficient of variation of CO measurements was 5.1%. One minute after CPB the temperature change was -0.144 degrees C/min, producing a CO measurement error of -0.57 +/- 0.52 l/min (SD), or about 11% of the average CO; the range of the error was 0.05 to -2.0 l/min. Ten minutes after CPB the temperature change was -0.063 degrees C/min, and CO error was -0.31 +/- 0.36 (0.15 to -1.20) l/min. At 30 min the temperature change was -0.012 degrees C/min (not significant), and CO error was -0.13 +/- 0.14 l/min. Duration of CPB was 104 +/- 30 min, with rewarming for 44 +/- 13 min; the average minimum bladder temperature was 25.1 +/- 2.3 degrees C during cooling and 36.7 +/- 0.7 degrees C at the end of CPB. Under these conditions TDCO measurements within the first 10 min after CPB often underestimate the true CO. PMID- 1610009 TI - The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification. AB - The role of desmopressin acetate in attenuating blood loss and reducing homologous blood component therapy after cardiopulmonary bypass is unclear. The purpose of this investigation was to identify a subgroup of patients that may benefit from desmopressin acetate therapy. One hundred fifteen patients completed a prospective randomized double-blind, placebo-controlled trial designed to evaluate the effect of desmopressin acetate (0.3 microgram.kg-1) on mediastinal chest tube drainage after elective coronary artery bypass grafting surgery in patients with normal and abnormal platelet-fibrinogen function as diagnosed by the maximal amplitude (MA) on thromboelastographic (TEG) evaluation. The 115 patients evaluated were divided into two groups based on the MA of the post cardiopulmonary bypass TEG tracing. Group 1 (TEG:MA greater than 50 mm) consisted of 86 patients, of whom 44 received desmopressin and 42 received placebo. Twenty nine patients had abnormal platelet function (TEG:MA less than 50 mm) and were designated as group 2. In group 2, 13 received desmopressin and 16 placebo. During the first 24 h after cardiopulmonary bypass, the placebo-treated patients in group 2 had significantly greater mediastinal chest tube drainage when compared to placebo patients in group 1 (1,352.6 +/- 773.1 ml vs. 865.3 +/- 384.4 ml, P = 0.002). In addition to increases in blood loss, group 2 placebo patients also were administered an increased number of blood products (P less than 0.05). The desmopressin-treated patients in group 2 neither experienced increased mediastinal chest tube drainage nor received increased amounts of homologous blood products when compared to those in group 1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610010 TI - Differences between aortic and radial artery pressure associated with cardiopulmonary bypass. AB - Previous investigators have identified an aortic-to-radial artery pressure gradient thought to develop during rewarming and discontinuation of cardiopulmonary bypass. The authors measured mean aortic and radial artery pressures before, during, and after cardiopulmonary bypass in 30 patients, to determine when the pressure gradient develops. The pressure gradient was also measured before and after intravenous injections of sodium nitroprusside (1 microgram/kg) and phenylephrine (7 micrograms/kg) to determine the effect of changes in systemic vascular resistance. A significant (P less than 0.05) pressure gradient (mean +/- SEM = 4.9 +/- 0.7 mmHg) developed upon initiation of cardiopulmonary bypass. This gradient did not change significantly during the middle of bypass (4.2 +/- 0.5 mmHg), with rewarming (4.8 +/- 0.7 mmHg), immediately prior to discontinuation of bypass (4.6 +/- 0.7), or 5 and 10 min following bypass (4.9 +/- 0.9 and 4.8 +/- 0.7 mmHg). Sodium nitroprusside significantly decreased systemic vascular resistance, by 15 +/- 2%, during the middle of bypass but did not affect the pressure gradient. Likewise, phenylephrine increased the systemic vascular resistance by 52 +/- 6% and 34 +/- 4% during the middle of bypass and rewarming, respectively, without affecting the pressure gradient. Although the exact mechanisms responsible for the pressure gradient remain unknown, these results suggest its etiology is associated with events occurring during initiation of cardiopulmonary bypass rather than with rewarming or discontinuation of cardiopulmonary bypass. PMID- 1610011 TI - Relative risk analysis of factors associated with difficult intubation in obstetric anesthesia. AB - Difficult tracheal intubation, often unexpected, has been identified as the commonest contributory factor to anesthetic-related maternal death. The ability to predict such cases preoperatively would be of great value. Preoperative airway assessment and potential risk factors for difficult tracheal intubation were recorded in 1,500 patients undergoing emergency and elective cesarean section under general anesthesia. Airway assessment using a modified Mallampati test recorded oropharyngeal structures visible upon maximal mouth opening. Potential risk factors documented were obesity; short neck; missing, protruding, or single maxillary incisors; receding mandible; facial edema; and swollen tongue. Subsequent to induction of anesthesia, the view at laryngoscopy and difficulty at intubation were graded. There was a significant (P less than 0.001) correlation between the oropharyngeal structures seen and both the veiw at laryngoscopy and difficulty at intubation. Univariate analysis demonstrated a significant association between difficult intubation and short neck (P less than 0.001), obesity (P less than 0.0001), missing maxillary incisors (P less than 0.02), protruding maxillary incisors (P less than 0.001), single maxillary incisor (P less than 0.0001), and receding mandible (P less than 0.003). Neither facial edema (P = 0.414) nor swollen tongue (P = 0.141) were found to be associated with difficult intubation. Multivariate analysis removed obesity and missing and single maxillary incisors as risk factors. Obesity was eliminated because of its strong association with short neck. The probability of experiencing a difficult intubation for various combinations of risk factors was determined.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610012 TI - Influence of lidocaine on leukocyte function in the surgical wound. AB - The inflammatory response of the wound is mediated to a large extent by leukocytes, which play an important role in the wound healing process. Local anesthetics, which are routinely administered before minor skin surgery and for postoperative pain relief, have been shown to have diverse effects on wound healing. Local anesthetics have also been reported to induce potent inhibition of leukocytes in vitro, although their effects on leukocyte activity in the surgical wound have not been elucidated. The present study investigated the in vivo effects of lidocaine on leukocyte function in the surgical wound of rats by sampling leukocytes from hollow titanium implants. The surgical wound was treated with lidocaine or placebo after implantation of the titanium chamber and before skin closure. Leukocyte metabolic activity was measured by chemiluminescence. Cell count was analyzed in a Burker chamber. Results showed progressive increase in leukocyte counts in the wounds of control animals and significantly lower cell counts in the wounds of lidocaine-treated animals 48 h (P less than 0.05) and 72 h (P less than 0.05) after surgery. A pronounced inhibition of the metabolic response to serum-opsonized zymosan was seen after 8 h in the lidocaine-treated animals versus controls (P less than 0.05). After 24 h, leukocyte metabolic activity decreased dramatically in the control group and remained at a low level until 72 h after surgery. In the lidocaine-treated group, the leukocyte response to zymosan remained constantly low throughout the study. The effects of lidocaine were not a result of impaired leukocyte viability.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610013 TI - Brain edema and neurologic status following head trauma in the rat. No effect from large volumes of isotonic or hypertonic intravenous fluids, with or without glucose. AB - Disagreement exists regarding the need to restrict the administration of fluid and glucose following head injury to prevent cerebral edema and neurologic deterioration. We examined whether blood osmolality and glucose, neurologic outcome, and the development of brain edema following head trauma were altered by intravenous infusion of large volumes of isotonic or hypertonic fluids that contained or did not contain glucose. Fifty-five rats that survived ether anesthesia and closed head trauma (delivered using a weight drop device) were assigned to one of five groups. In the first group no fluid was infused. In the second group minimal volumes of saline were infused during placement of a jugular vein catheter. In the three remaining groups 10 ml.kg-1.h-1 of either total parenteral nutrition (TPN) (glucose 25%, amino acids 4.25%, 40 mEq/l sodium and 40 mEq/l potassium, 1935 mOsm/kg), dextrose 5% in 0.45% saline (495 mOsm/kg), or Haemaccel (isotonic plasma expander, 298 mOsm/kg) was infused via the jugular vein. Following head trauma and cannula placement, ether was discontinued. Neurologic severity score at 1 and 18 h after head trauma was used to assess neurologic outcome. A score between 0 and 6 was assigned by an observer who was blinded as to the experimental groups, with 0 representing no neurologic damage and 6 representing severe damage. Specific gravity of brain tissue samples containing gray matter and subcortical white matter from the traumatized and contralateral hemispheres was measured at 18 h after head trauma to determine the development of brain edema. There were no statistically significant differences in neurologic outcome and brain edema between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610014 TI - Effects of aminophylline on regional diaphragmatic shortening after thoracotomy in the awake lamb. AB - Aminophylline has been reported to augment diaphragmatic contraction, although this remains a controversial finding. We studied the effect of aminophylline on regional diaphragmatic shortening, changes in transdiaphragmatic pressure (delta Pdi), and integrated regional electromyographic (EMG) activity of the diaphragm (Edi) after a right thoracotomy in nine lambs using sonomicrometry, esophageal and gastric balloons, and EMG. Sonomicrometer crystals and EMG leads were implanted into the costal and crural regions of the diaphragm through a right thoracotomy, and a tracheostomy was performed. The animals were studied while awake within 4 days after surgery. Fractional costal and crural diaphragmatic shortening was measured using the sonomicrometer; delta Pdi was calculated from esophageal and gastric pressures. Respiratory variables were measured through the tracheostomy. Data were collected during quiet breathing and during CO2 rebreathing. After control measurements, aminophylline (10 mg/kg) was administered intravenously, producing a serum concentration of 17.7 +/- 1.5 micrograms/ml. Aminophylline did not augment shortening, increase delta Pdi, or overcome postoperative diaphragmatic inhibition acutely in the awake sheep after a right lateral thoracotomy. A small decrease of end-tidal CO2, from 5.2% to 4.9%, was measured at rest during aminophylline infusion, but Edi was unchanged. Although during CO2 rebreathing diaphragmatic shortening increased, the addition of aminophylline did not further augment shortening. Our data in awake lambs suggest that aminophylline does not improve diaphragmatic contraction in the acute postoperative period. PMID- 1610015 TI - Australian-German collaborative studies on the immunology of Sarcocystis infections. AB - This paper reviews a decade of collaborative studies performed between two laboratories in Germany and Australia on the life cycle, pathogenicity and immunology of infections by the cyst-forming sporozoan parasites Sarcocystis spp. in domestic animals. Experimental transmission studies demonstrated that certain parasite species could cause an acute clinical disease in sheep and pigs severely affecting their health, productivity and reproductivity. Despite the high prevalence of infections found in farm animals, few outbreaks of naturally occurring clinical disease have ever been recorded. Host animals exposed to low levels of infection were found to develop a strong protective immunity against subsequent lethal challenge and clinical disease even though parasites were not completely eliminated nor prevented from further establishment (premunitive immunity rather than sterile immunity). Modern molecular biological techniques are currently being used to examine the parasite antigens and host immune responses involved in the acquisition of the protective immunity. PMID- 1610016 TI - [In vivo observations of the division of the oversized round forms of Trichomonas vaginalis in culture]. AB - Continuous in vivo observations of the behaviour of multinucleate, multiflagellate forms of Trichomonas vaginalis have been made in a microchamber at 36 degrees C. It has been proven that these forms are initial forms of the multiplication of the parasite by cell division. Serial in vivo shots have been taken in this microchamber of the budding of a young flagellate from a multinucleate, multiflagellate form. In vivo observations have shown that these round forms are multiplicable, living cell forms of the parasite. PMID- 1610017 TI - Incidence of Mallophaga on poultry in Dehradun (India). AB - The order of abundance of different mallophagan species on poultry birds in Dehradun (India) has been found to be Menopon gallinae greater than Menacanthus cornutus greater than Menacanthus stramineus greater than Goniocotes gallinae greater than Goniodes dissimilis greater than Lipeurus caponis greater than Lipeurus lawrensis tropicalis greater than Goniodes gigas. The intensity of these species upon 1249 birds has been recorded by coding system. The correlation between the monthly incidence of different species and environmental temperature as well as R.H. has been recorded. The degree of association between four most commonly occurring combinations has also been analysed. PMID- 1610018 TI - [The therapy of swimbladder inflammation (renicola sphaerosporosis) of carp]. AB - In pond experiments the efficiency of different chemotherapy variants against swimbladder inflammation (SBI) was proved. Only by feeding of Fumagillin, specifically affecting Myxosporidians, the infection of kidney with Sphaerospora renicola as well as the force of SBI could be reduced. The chemotherapy with Metronidazole remained inefficacious, whereas the permanent feeding with Methylene blue prevented only the infection with Bothriocephalus acheilognathi and probably lowered insignificantly the breeding-losses on this way. Water conditioning by means of chloride of lime only lowered the losses caused by gill necrosis, on SBI it had no influence. A relationship between gill necrosis and SBI, that seemed to be possible, could not been corroborated. PMID- 1610019 TI - Indications for the use of intravenous gammaglobulin. PMID- 1610020 TI - Asthma-producing drugs. PMID- 1610021 TI - Headaches, muscular weakness, and IgA deficiency. PMID- 1610022 TI - Hypogammaglobulinemia in asthmatic patients. AB - We measured quantitative immunoglobulins (IgG, IgA, IgM, and IgG subclasses) in 101 unselected asthmatic patients. We identified hypogammaglobulinemia in 12 patients primarily involving IgG (dose-related) without a strong prediction for any IgG subclass. IgA and IgM were also suppressed but to a lesser extent. This prevalence of hypogammaglobulinemia (.12 +/- standard error of .03) is significantly greater than that seen in the normal population (approximately .025 +/- .017, P = .01). Hypogammaglobulinemia was strongly associated with use of systemic corticosteroids (P = .0001). A cumulative steroid dose of greater than or equal to 5 mg/day for at least 2 years was found in 10/12 patients with hypogammaglobulinemia compared with 37/89 patients without hypogammaglobulinemia (P = .024). No significant increase in the number of infectious episodes was seen in the hypogammaglobulinemic patients. To assess the significance of hypogammaglobulinemia in asthmatics, we assessed responses to tetanus and pneumococcal vaccine in three groups of asthmatics: (1) those with total IgG less than 400 mg/dL who had been on chronic oral steroids, (2) those with total IgG between 855 and 1199 mg/dL who were currently receiving oral steroids, and (3) those with total IgG between 855 and 1199 mg/dL who were not receiving oral steroids. All patients responded normally to tetanus vaccine, but three of eight patients in the hypogammaglobulinemic group showed impaired responses to pneumococcal vaccine. Patients with impaired pneumococcal responses were not clearly distinguishable on the basis of sinus disease or pneumonia. We conclude that although many patients with severe, steroid-dependent asthma experience repeated episodes of bronchitis or exacerbations of sinusitis, these problems are rarely associated with an impairment in specific antibody production. IgG subclass deficiencies are not common in this patient population. A very small subgroup of patients manifest a more severe hypogammaglobulinemia (IgG less than 400 mg/dL) or an inordinate frequency of infectious episodes. Given that bronchitis or sinusitis can be attributed to factors other than hypogammaglobulinemia in these patients, an assessment of specific antibody production in response to pneumococcal vaccination is warranted. A small but significant percentage of such patients will demonstrate impaired responses. These patients should be considered at increased risk for bacterial infections and should, therefore, be monitored closely for infectious episodes. PMID- 1610023 TI - Squid hypersensitivity: a clinical and immunologic study. AB - Hypersensitivity to mollusk has rarely been described in the literature. Among the mollusks, the cephalopods are a group of great importance as a food source. We report seven patients who had had symptoms highly suggestive of IgE-mediated reactions after ingesting squid or inhaling vapors from cooking squid. All had previously suffered from persistent rhinitis or asthma for years. In addition, six of the seven patients had had symptoms after ingesting shrimp. Skin prick tests were strongly positive for boiled squid extract and for various commercial crustacean extracts. Specific IgE antibodies against boiled extract and several crustacean extracts were demonstrated in all patients by RAST and reverse enzyme immunoassay. Cross reactivity between squid and shrimp and other crustaceans was demonstrated by reverse immunoassay inhibition studies. Cross reactivity could not be demonstrated between squid and octopus, which are both cephalopods, nor between squid and other mollusks. PMID- 1610024 TI - Pemirolast, a new oral nonbronchodilator drug for chronic asthma. AB - Pemirolast is a new oral, nonbronchodilator antiallergy medication that is being evaluated for the therapy of asthma. In this multicenter, double-blind, randomized study, 96 patients with mild asthma received pemirolast, 50 mg (n = 34); pemirolast, 25 mg (n = 31); or placebo (n = 31) BID for 6 weeks. Patients were evaluated weekly at the research centers; they maintained daily symptom diaries and measured peak expiratory flow rates twice a day. Methacholine challenge was performed at the start and end of the study. Results with pemirolast, 50 mg BID, showed statistically significant decrease in nocturnal symptoms (P = .02), in composite symptom scores (P = .02) and in bronchodilator use (P = .05) when compared with placebo. There were no statistically significant differences between treatments in pulmonary function tests or in methacholine challenge sensitivity. Pemirolast, 25 mg BID, did not differ from placebo. There were no significant adverse effects. Pemirolast, 50 mg BID, demonstrated sufficient antiasthma activity to warrant further studies in patients with more severe asthma and with higher doses. PMID- 1610025 TI - Incidence of systemic reactions during rush immunotherapy. AB - Rush immunotherapy (RIT) was administered on an outpatient basis to 11 patients. Of these, nine had asthma and four were steroid-dependent. All patients received extracts containing a mixture of antigens to which they were prick-sensitive. FEV1s were greater than 80% predicted before starting RIT. Four patients each required a 1 week steroid "burst" to accomplish this. A series of 8 subcutaneous injections were given starting with 0.3 mL of 1:100,000 (wt/vol) and ending with 0.10 mL of 1:100 (wt/vol) 1.5 days later. A dose of 0.15 mL of 1:100 was given weekly after that. All patients but one completed the RIT. Four had sore arms, four had pruritus and/or sneezing, four developed wheezing, and one experienced anaphylaxis with hypotension. Systemic reactions tended to occur at the higher doses and usually more than 30 minutes after a previous injection. Subsequent weekly injections were tolerated without reactions by seven of the patients. Rush immunotherapy is an effective method for administering a high dose of allergen in a very short time period. Due to the risk of systemic reactions it needs to be given under carefully controlled conditions. PMID- 1610026 TI - Once-a-day dosing with theophylline: a comparison of four sustained-release products. AB - This study compared once-a-day dosing of Slo-bid, Theo-Dur, Theo-24 and Uniphyl, sustained release theophylline preparations, in the treatment of 12 mild to moderate asthmatic patients (FEV1 greater than 60%). Eight hundred milligrams was given once-a-day in the morning for 2 weeks for each drug in this 4-way, crossover, open-label study. At the end of each 2-week period, pharmacokinetics were assessed by measuring theophylline levels every two hours for 24 hours. Efficacy was evaluated by spirometry, physical examination, daily peak flow measurements, and daily symptom diaries. In an additional 2-week period, Slo-bid 800 mg, was taken once-a-day after the evening meal and the same measures of pharmacokinetics and efficacy were performed. Slo-bid (range 8.8, coefficient variation 19.5) exhibited significantly less intrapatient variability than Theo Dur (range 12.2, coefficient of variation 36.5) and Theo-24 (range 8.2, coefficient of variation 25.8). Patients taking Slo-bid also had significantly better evening peak flow values than patients taking Theo-Dur (424.5 L/min versus 395.4 L/min). Analysis of other measures of theophylline pharmacokinetics (area under the curve, minimum serum level, occupancy times) as well as diary variables, physical examination findings, and spirometry values showed no differences among the four formulations, although expected individual variability in pharmacokinetics was observed. When Slo-bid was dosed in the evening, higher blood levels were achieved compared with morning administration, suggesting a therapeutic advantage of evening dosing with this product. PMID- 1610027 TI - Age of onset in childhood asthma: data from a national cohort. AB - There is controversy over the role of age of asthma onset in childhood asthma. Data collected on self-reported physician-diagnosed asthmatic children and young adults aged 6-24 years (N = 352), who participated in the second National Health and Nutritional Examination, 1976-80 (NHANES II), a national sample, were examined to see whether reported age at onset was associated with the future course of the asthma. Three definitions were used for early-onset asthma: asthma beginning before the second birthday, before the third birthday, and before the fourth birthday. Late-onset asthma was defined as asthma beginning on or after the second birthday, the third birthday, and the fourth birthday, respectively. Among 6-14 year olds, late-onset asthmatic subjects as compared with early-onset asthmatic subjects using the three definitions reported more allergic rhinitis OR = 3.79 (95% CI 1.53, 9.41), 3.06 (1.33, 7.07), 2.71 (1.18, 6.22), and were more likely to have at least one positive allergen skin test OR = 2.21 (95% CI 1.02, 4.79), 2.90 (1.29, 6.49), 3.41 (1.50, 7.75). Late-onset asthmatic subjects tended to report that their asthma was active, have more problems during the past 12 months with wheezing, and have lower values for predicted FVC and FEV1. No difference was found in reported chronic rhinitis, sinusitis, other allergies, problems within the last 12 months with cough attacks, or during the past 3 years a period of cough and phlegm lasting more than 3 weeks.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610028 TI - Age-related changes in specific IgE antibody production. AB - We measured specific IgE antibodies to mites and Japanese cedar pollen (JCP) in a general population aged from 18 to 99 years by fluorescence enzyme immunoassay and analyzed the relationship of antigen-specific IgE antibody production to aging. The incidence of mite antibody carriage gradually decreased in proportion to age from 26.7% at 18 to 19 years of age to 15.9% for the 60 to 69 age group and then decreased markedly in the subjects aged 70 and over. A similar tendency was found with regard to JCP antibody positivity. The highest levels of antibodies to both mites and JCP were found in young adults, and these levels decreased with age. There was a significant negative correlation between the mean relative fluorescence unit value for specific IgE antibodies and age (mite antibody: r = -.957 and JCP antibody: r = -.954). No significant correlation was found between mite antibody levels and JCP antibody levels in the individual subjects. PMID- 1610029 TI - Prevalence of asthma in a tropical city of Colombia. AB - Four thousand subjects from Cartagena, Colombia were surveyed in order to establish the prevalence of asthma in this city. They were considered to have asthma when they had consulted their physicians for shortness of breath accompanied with wheezing during the last year and had received asthma medications. Point and cumulative prevalence were 8.8% and 12.2%, respectively. Seventy percent of the affected population was less than 15 years old. There were no significant differences in the prevalence of asthma between sexes. Forty-five percent of asthmatic subjects had family histories of asthma. The prevalence of rhinitis was 16.4% and 30.6% of the patients with asthma. The asthma prevalence of this study is high, indicating that this respiratory disease is a significant health problem in this tropical city. PMID- 1610030 TI - Relationship between arterial blood gas tensions and a clinical score in asthmatic children. AB - In order to evaluate the severity of acute asthma in young children, we used the clinical scoring system devised by Mitsui. This scoring system is constructed by reference only to clinical symptoms and signs such as dyspnea, wheezing, auscultation of rales, speech impairment, cyanosis, and mental status. All patients were less than 5 years old. The clinical scores had a statistically significant correlation with PaO2. High scores definitely were associated with hypoxemia but low scores did not exclude hypoxemia. Scores showed good correlation with the values of PaCO2 compared with the values of PaO2. Scores under 3 were associated with PaCO2 values less than 40 mmHg; scores over 7, with PaCO2 over 40 mmHg. Reproducibility was good, and there was a good relationship between scores and blood gas tensions in individuals. Rales correlated with PaO2. Dyspnea and cyanosis had good correlation with PaCO2. PMID- 1610031 TI - Grand mal seizures temporally related to cocaine use: clinical and diagnostic features. AB - STUDY OBJECTIVES: To determine the appropriate diagnostic workup of the emergency department patient with an uncomplicated cocaine-related grand mal seizure. DESIGN SETTING: Retrospective analysis. A city and county ED with 45,000 selected visits per year. TYPE OF PARTICIPANTS: Thirty-seven patients with acute grand mal seizure after cocaine exposure were studied. All had historical or laboratory evidence of cocaine use and no history of prior seizure disorder. INTERVENTIONS: The diagnostic workup varied among patients. Most received computed head tomography (35), whereas fewer received-ECG (18), EEG (16), and lumbar puncture (six). MEASUREMENTS AND MAIN RESULTS: Thirty-three patients with an uncomplicated cocaine-related seizure had an unremarkable series of diagnostic tests. The four patients with remarkable neurologic manifestations were compared with the remainder of patients who were without neurologic abnormalities. Comparison of groups by route of cocaine intake revealed no significant difference in the time interval to seizure (P = .761). CONCLUSION: Diagnostic workup probably is not indicated for the patient experiencing a cocaine-related generalized seizure who will recover promptly and have a normal postictal examination. PMID- 1610032 TI - Evaluation of the Vision Theophylline assays in the emergency department setting. AB - STUDY OBJECTIVES: To determine whether the use of fingerstick blood samples or venipuncture blood samples affect the accuracy and the precision of the Vision Theophylline I assay and the Vision Theophylline II assay in the emergency department setting. DESIGN: Prospective clinical trial. SETTING: ED in a university teaching hospital. SUBJECTS/INTERVENTIONS: Simultaneous fingerstick and venipuncture blood samples were obtained from adult patients who required baseline theophylline levels in the ED. MEASUREMENTS: The Vision system was used in the ED to measure theophylline concentrations from fingerstick and venipuncture samples. Vision samples were drawn and analyzed by one of three pharmacists rounding within the ED between March and October 1990. These pharmacists were instructed by laboratory personnel concerning pertinent operating procedures. The vision Theophylline I and Theophylline II assays are enzyme-inhibitor immunoassays contained within a multi-chamber test packet. The high-performance liquid chromatography (HPLC) theophylline assay was used as the reference method. MAIN RESULTS: Linear regression of theophylline concentrations determined by the Vision Theophylline I assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9440; P less than .05) and for venipuncture samples (r = .9750; P less than .05). The accuracy values for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were -0.63 +/- 1.2 mg/l and 0.22 +/- 1.8 mg/L, respectively. The precision for Vision Theophylline I assay venipuncture and fingerstick samples versus HPLC were 0.27 and 0.38, respectively. Linear regression of theophylline concentrations determined by the Vision Theophylline II assay versus HPLC revealed a significant correlation for fingerstick samples (r = .9804; P less than .05) and for venipuncture samples (r = .9875; P less than .05). Accuracy values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were -0.53 +/- 1.4 mg/L and -0.65 +/- 1.3 mg/L, respectively. Precision values for Vision Theophylline II fingerstick and venipuncture samples versus HPLC were 0.34 and 0.29, respectively. CONCLUSION: There is a strong correlation between theophylline concentrations measured by Vision Theophylline assay versus HPLC, regardless of whether the Vision Theophylline assay is performed on a fingerstick or venipuncture sample. Vision fingerstick samples were more accurate than Vision venipuncture samples for both Vision Theophylline I and II assays. Theophylline concentrations measured by the Vision system using venipuncture samples were slightly more precise than those using fingerstick samples when compared with HPLC analysis. These differences in accuracy and precision were not clinically relevant. PMID- 1610033 TI - Antivenin administration for Centruroides scorpion sting: risks and benefits. AB - STUDY OBJECTIVES: To assess the clinical severity of envenomation by the Centruroides scorpion in young children; the potential benefit of antivenin administration with regard to time to resolution of symptoms, prevention of hospitalization, and prevention of invasive intervention; and the risk of acute and delayed hypersensitivity reaction. DESIGN: Retrospective chart review with follow-up contact. SETTING: Referral toxicology management center. TYPE OF PARTICIPANTS: Children less than 10 years of age experiencing severe Centruroides scorpion envenomation. INTERVENTIONS: Administration of goat serum-derived anti Centruroides antivenin. MEASUREMENTS AND MAIN RESULTS: Stings in young children may be life threatening, resulting in extreme neuromuscular activity, tachycardia, and respiratory distress. Administration of anti-Centruroides antivenin resulted in rapid resolution of all symptoms without acute reaction in all 12 patients so treated; 58% of patients treated with antivenin had a delayed onset of rash or symptoms of serum sickness. CONCLUSION: The benefit of rapid resolution of life-threatening symptoms and potential for outpatient management of severe envenomation in young children may justify the risk of acute and delayed reaction associated with antivenin use in this group. The use of antivenin for the less severe envenomation common in older children and adults may subject them to unjustified risk. PMID- 1610034 TI - Care of the elderly in emergency departments: where do we stand? PMID- 1610035 TI - Geriatric emergency medicine: a survey of practicing emergency physicians. AB - STUDY OBJECTIVES: To evaluate the current status of clinical, educational, social, ethical, and resource issues related to the care of the elderly among practitioners of emergency medicine. DESIGN: A mailed survey instrument. SETTING: None. TYPE OF PARTICIPANTS: Practicing emergency physicians randomly drawn from the membership list of the American College of Emergency Physicians. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 971 surveys were mailed, with 433 usable surveys among the 485 (50%) respondents. The surveyed emergency physicians anticipated a major impact on emergency department patient flow and bed availability in the hospital and ICU as the population ages. For each of seven clinical presentations (abdominal pain, altered mental status, chest pain, dizziness/vertigo, fever without a source, headache, multisystem trauma), 45% or more of the emergency physicians have more difficulty in the management of older compared with younger patients. Most respondents reported that each of these presentations required more time and resources for older patients. The majority believed research, the availability of continuing medical education, and time spent during residency training regarding geriatric emergency medicine was inadequate. CONCLUSION: Practicing emergency physicians are uncomfortable with elderly patients, and this may reflect the inadequacies of training, research, and continuing education in geriatric emergency medicine. PMID- 1610036 TI - Geriatric patient emergency visits. Part I: Comparison of visits by geriatric and younger patients. AB - OBJECTIVES: To describe emergency department use by the elderly, to define problems associated with emergency care of the elderly, and to compare these results with those for younger adult patients. DESIGN: Retrospective, controlled chart review. SETTING: Six geographically distinct US hospital EDs. PARTICIPANTS: From each site, a stratified sample (approximately 7:3) of elderly (65 years or older) and nonelderly (21 to 64 years old) control patients treated during the same time period was used. METHODS: Standardized review of ED records and billing charges. Comparisons of elderly and control patient groups using chi 2 analysis and Mann-Whitney U test (alpha = 0.05). RESULTS: Four hundred eighteen elderly patients and 175 nonelderly controls were entered into the study. The elderly were more likely to arrive by ambulance (35% versus 11%; P less than .00001). More elderly than controls presented with conditions of either high or intermediate urgency (78% versus 61%; P less than .0003). The elderly more frequently presented with comorbid diseases (94% versus 63%; P less than .00001). Other findings for the elderly included a longer mean stay in the ED (185 versus 155 minutes; P less than .003), higher laboratory (78% versus 53%; P less than .00001) and radiology (77% versus 52%; P less than .00001) test rates, higher mean overall care charges ($471 versus $344; P less than .00001), and an admission rate (47% versus 19%; P less than .00001) twice that of younger adults. CONCLUSION: Resource use and charges associated with emergency care are higher for the elderly than for younger patients. Increases in emergency resources and personnel or improvement in efficiency will be needed to maintain emergency care at present levels as the US population continues to grow and age. PMID- 1610037 TI - Geriatric patient emergency visits. Part II: Perceptions of visits by geriatric and younger patients. AB - OBJECTIVES: To compare group perceptions of reasons for emergency department care, ED use patterns, and the effect of illness on self-care ability for elderly and younger adult patients. DESIGN: Patient survey. SETTING: Six geographically distinct US hospital EDs. PARTICIPANTS: From each site, a stratified sample (approximately 7:3) of elderly (65 years and older) and nonelderly (21 to 64 years old) control ED patients treated during the same time period was contacted. METHODS: Three hundred ninety-nine elderly patients and 172 adult controls were interviewed using a structured survey instrument. Groups were compared using chi 2 analysis and the Mann-Whitney U test. RESULTS: Both the elderly and the control patients (49% versus 38%) commonly stated that the most important reason for coming to the ED was because they were "too sick to wait for an office visit." Of patients with a regular physician, both groups often were referred to the ED by their primary care provider (35% versus 26%). While the elderly had more visits to their primary care provider (3.3 versus 2.9 visits; P less than .00001), there was no difference in the number of ED visits (1.5 versus 1.6 visits) during the preceding six months. Of those released from the ED, more elderly noted deterioration in their ability to care for themselves as a result of their illness (21% versus 11%; P less than .03). CONCLUSION: The elderly use the ED for reasons similar to those for younger adults. Often they feel too ill to wait for an office visit or are referred in by their primary care provider. Elderly patients more commonly have difficulty with self care after release home, and emergency physicians must plan accordingly. PMID- 1610038 TI - Perceptions of emergency care by the elderly: results of multicenter focus group interviews. AB - STUDY OBJECTIVE: To determine the elderly's perception of emergency care and to identify specific problems and solutions. DESIGN: Focus group interviews. SETTING AND TYPE OF PARTICIPANTS: Community senior citizen centers in Boston; Los Angeles; Pittsburgh; Youngstown, Ohio; and Norwalk, Connecticut. Senior citizens who had had emergency care in the past year participated. MEASUREMENT AND RESULTS: Participants were satisfied with their overall medical care. Long waits were a hardship for patients and their families. The elderly are not familiar with the process of emergency care. They were frightened by their injury or illness. Their anxiety was not allayed until they were informed of the nature of their illness and what their treatment and disposition was to be. The emergency department environment frequently made them uncomfortable. There was considerable confusion caused by the billing process. CONCLUSIONS: The elderly would benefit from prior or concurrent education regarding emergency care. Staff should be more sensitive to the anxiety felt by the elderly, should explain the reasons for delays in care, and what to expect. Patients should be informed of the nature and seriousness of their illness as soon as possible. Family and friends may be encouraged to stay with patients. The billing process needs to be clarified and simplified. PMID- 1610039 TI - Use of emergency departments by elderly patients: projections from a multicenter data base. AB - STUDY OBJECTIVES: To assess the use of emergency medical care by the elderly in the United States, including emergency department visits, level of ED care required, ambulance services, and hospital admission rate. SETTING AND PARTICIPANTS: A multicenter computerized data base of 70 hospitals in 25 states. DESIGN: A retrospective review of elderly patients seeking ED care and comparison of elderly and nonelderly patients. The data were then used to estimate the use of emergency medical services nationally. MEASUREMENTS AND MAIN RESULTS: Fifteen percent of the 1,193,743 ED visits were made by patients 65 years or older. Thirty-two percent of elderly patients seen in EDs were admitted to the hospital, compared with 7.5% of nonelderly patients. Seven percent of elderly patients were admitted to ICUs, compared with 1% of nonelderly patients. Thirty percent of elderly patients seeking emergency care used ambulance transports compared with 8% of nonelderly. It is estimated that 13,693,400 elderly patients were seen in EDs in 1990, with more than 4 million patients admitted to hospitals. Compared with the nonelderly, the elderly are 4.4 times more likely to use ambulance transport, 5.6 times more likely to be admitted to the hospital, 5.5 times more likely to be admitted to an intensive care bed, and 6.1 times more likely to be classified as a comprehensive ED level of service. In our sample, 36% of all patients arriving by ambulance to the ED, 43% of all ED admissions, and 48% of all intensive care admissions were geriatric patients. CONCLUSION: With the rapid growth of the size of the elderly population, it is important that we assess the emergency medical resources needed to care for the geriatric population. PMID- 1610040 TI - Geriatric training in emergency medicine residency programs. AB - STUDY OBJECTIVES: The health care needs of the elderly population are significantly different from those of younger patients and require special knowledge and skills on the part of emergency physicians. The purpose of this study was to identify the nature and extent of geriatric training currently provided to emergency medicine residents. DESIGN: Self-administered survey distributed to residency directors of the 85 accredited emergency medicine residency programs in the United States. INTERVENTIONS: The survey consisted of 17 questions focusing on residency directors' views about teaching and research of geriatric emergency care. RESULTS: Survey information was obtained from 85 (100%) emergency medicine residency programs. Forty percent (34 of 85) of respondents believed the teaching of geriatric emergency care was inadequate; 44 programs (52%) plan to increase the number of didactic hours devoted to geriatrics (mean increase of 5.9 hours). The five geriatric topics most frequently taught included acute dementia, atypical presentation of illness, common complaints in the elderly, geriatric trauma, and ethical issues. Sixty five percent believed ongoing national research efforts regarding geriatric emergency medicine were insufficient; 21 programs (25%) had faculty involved in geriatric studies. Most respondents reported that growing numbers of elderly will have a major impact on all areas of patient care in the near future. CONCLUSION: Although geriatric emergency care is becoming an integral part of the emergency medicine residency program, there may be a need for better focused and more intensive training. PMID- 1610041 TI - Care of the elderly in emergency departments: conclusions and recommendations. AB - Little attention is being paid to the special needs of elderly persons in emergency departments. Emergency health care professionals feel less comfortable caring for elderly than for nonelderly patients. The social and personal concerns of the elderly frequently are not addressed in ED encounters. There is a paucity of research and education in geriatric emergency medicine. Overall principles of care for elderly patients seeking emergency care have not been defined as they have for other special populations such as children. The disease-oriented model used for caring for nonelderly adult patients in EDs may not be appropriate for elderly patients. The emergency care of the elderly requires significantly more health care resources than does that of the nonelderly. Compared with nonelderly patients, elderly patients seeking emergency care are four times more likely to use ambulance services, five times more likely to be admitted to the hospital, five times more likely to be admitted to an intensive care bed, and six times more likely to receive comprehensive emergency services. Although 12% of the population is 65 years or older, this group accounted for 36% of all ambulance patient transports to EDs, 43% of all hospital ED admissions, and 48% of all critical care admissions from EDs. These problems are particularly important at this time because many hospitals and their EDs are faced with significant problems of overcrowding and inadequate resources to meet the health care needs of the communities they serve. Although the elderly are the fastest-growing segment of the population, little or no planning is ongoing to meet the emergency health care needs of the elderly in the future. The task force has provided specific recommendations for addressing these problems. PMID- 1610042 TI - Geriatric emergency care: an annotated bibliography. AB - This annotated bibliography provides selected references to journal articles addressing general issues of the care of elderly patients in the emergency department. The bibliography was compiled by the Society for Academic Emergency Medicine Geriatric Emergency Medicine Task Force. Because the literature pertinent to geriatrics has continued to grow rapidly, only key articles of general interest to the clinician and academician are included in the bibliography. Preference is given to recent publications; most references date from the past five years. The articles cited are primarily concerned with the delivery of emergency care to geriatric patients; economic, legal, ethical, and sociological topics receive limited coverage. Some articles were selected to highlight current controversies or changes in viewpoint. Aging physiology, atypical characteristics of illness, and disease processes have been addressed elsewhere (J Am Geriatr Soc 1989;37:894-910). PMID- 1610043 TI - Difficulty in predicting bacteremia in elderly emergency patients. AB - STUDY OBJECTIVES: To characterize the clinical presentation and identify factors predictive of bacteremia in elderly patients. DESIGN: Retrospective review of emergency department charts, hospital records, and microbiology reports. SETTING: Community teaching hospital with annual ED census of 65,000 adults. PARTICIPANTS: Seven hundred fifty elderly patients (aged 65 to 99 years) who were evaluated by the emergency physician, had blood cultures obtained in the ED, and were hospitalized with a suspected infectious process during a 12-month period. MEASUREMENTS: Records were analyzed for demographic information, underlying diseases, clinical presentation, laboratory findings, sources of infection, and causative organisms. Using contingency tables, 79 patients with positive blood cultures were compared with a random sample of 136 patients with sterile blood cultures to identify clinical variables significantly (P less than .05) associated with bacteremia. Logistic regression analysis was performed with significant factors to develop a model to predict bacteremia. Sensitivity, specificity, and predictive values were calculated for the model. MAIN RESULTS: The prevalence of bacteremia was 10.6%. Escherichia coli was the most commonly isolated pathogen (29% of cases), and the urinary tract was the most common source of infection (44.3% of cases). Logistic regression analysis showed that altered mental status (odds ratio, 2.88; 95% confidence interval [Cl], 1.52 to 5.50), vomiting (odds ratio, 2.63; 95% Cl, 1.16 to 6.15), and WBC band forms of more than 6% (0.06) (odds ratio, 3.50; 95% Cl, 1.58 to 5.27) were independent predictors of bacteremia. The presence of at least one of these three factors had a sensitivity of 0.85 (95% Cl, 0.75 to 0.92) and a specificity of 0.46 (95% Cl, 0.38 to 0.55) for predicting bacteremia in the study group. The positive predictive value was 0.16 (95% Cl, 0.12 to 0.19) and the negative predictive value was 0.96 (95% Cl, 0.94 to 0.98) for the ED patient group that met inclusion criteria. CONCLUSION: Elderly patients fail to manifest identifiable clinical features indicative of bloodstream infection. The sensitivity and specificity of the best statistical model for identifying bacteremic elderly patients suggest that clinical indicators alone are unreliable predictors of bacteremia in the geriatric ED population studied. PMID- 1610044 TI - Pseudoephedrine for the prevention of barotitis media: a controlled clinical trial in underwater divers. AB - STUDY OBJECTIVE: To determine the efficacy and safety of decongestant prophylaxis among first-time underwater divers in the prevention of barotitis media (middle ear squeeze). DESIGN: Randomized, double-blind, prospective clinical trial. SETTING: Recreational diving schools in Panama City, Florida. TYPE OF PARTICIPANTS: One hundred twenty volunteer scuba divers under the supervision of certified instructors. INTERVENTIONS: After randomization, each subject received a 60-mg tablet of pseudoephedrine or placebo 30 minutes before diving. Prospective data were collected, including subject demographics, signs and symptoms of middle ear squeeze during the dive, and possible drug side effects. The otoscopic appearance of the tympanic membrane was graded according to the amount of hemorrhage in the eardrum, with Teed scores ranging from 0 (normal) to 5 (gross hemorrhage and rupture). chi 2 and t-tests were applied with significance set at P less than .05). The Mantel-Haenszel test was used to test the null hypothesis that the mean Teed scores of the two treatment groups were equal. RESULTS: A total of 116 subjects met the inclusion criteria and completed the study; 60 received 60 mg pseudoephedrine, and 56 received placebo. The treatment groups were similar with regard to age, sex, medical history, and depth of the first dive (P greater than .5). Ear discomfort and blockage during the dive were present in 8% (five of 60) of those receiving pseudoephedrine versus 32% (18 of 56) of the control group (P = .001). Similarly, the pseudoephedrine group had smaller Teed scores after diving than did the control subjects (P = .003). Adverse effects were minimal; two patients experienced dizziness and nausea. CONCLUSION: These results suggest that the use of an oral decongestant before diving decreases the incidence and severity of middle ear squeeze in novice divers. PMID- 1610045 TI - "What's in a name?," "Moonlighting for fun and profit": reflections on the state of emergency medicine--a goal for 2000 and beyond. AB - We are perhaps America's greatest source of unquestioned and unquestioning care for the poor. The acutely ill and injured need us desperately, every hour of every day. No one who comes to the door of any ED needing our services fails to receive our best efforts. Emergency physicians freely place themselves at risk from violence and the deadliest of diseases. We should be at the pinnacle of public and professional admiration and respect. Yet parents are told their children are at risk, no one knows our names, and hospital administrators and medical staffs watch us come and go with equanimity. Our work is occasionally thrilling, often repetitive, quite frequently sad, sometimes dangerous, generally described as stressful, and on occasion incredibly rewarding. Both one's individual job satisfaction and the collective survival of our specialty depend on the mix of these factors being satisfying enough to justify going to work every day. Some of that job satisfaction must come from outside ourselves, the perception that what we do is valued by others. How much "burnout" derives from a growing awareness of how negatively we are viewed and how little that perception has changed. To the extent that organized emergency medicine wishes to keep the specialty alive and healthy, it must address this image crisis in emergency medicine. What is the purpose of looking past the year 2000 with lofty goals and aspirations if, through the eyes of our peers and patients, we have come such a little way? As much as I appreciate the opportunity to write this editorial, we in emergency medicine need to do more than preach to ourselves. A little at a time, in every way we can, in academic centers or 40-bed hospitals, as members of the medical staffs and hospital committees, and in our day-to-day interactions with our peers, students, and the public, we must demand our name and demand the recognition we have won for our (apparently) still fledgling specialty. Our organizations must represent us in these areas by forcefully directing their public relations efforts away from ourselves and toward the public and our colleagues. PMID- 1610046 TI - Chemical warfare agents: II. Nerve agents. AB - Nerve agents are highly potent and rapidly acting organophosphorus compounds that irreversibly bind and inactive acetylcholinesterase. Only rarely have they been used in warfare, but their great lethality and the threat that they pose have encouraged production and stockpiling in large quantities. They differ in a number of important ways from common agricultural organophosphate insecticides. In light of recent threats of chemical warfare and the possibilities of chemical acts of terrorism, North American physicians should be knowledgeable of the effects of these agents and the care of exposure victims. PMID- 1610047 TI - Metal fume fever. AB - Metal fume fever is an ancient occupational disease still encountered among metal workers. The delay between exposure and onset of non-specific symptoms makes this an elusive diagnosis. We present the case of a patient who developed symptoms several hours after welding. The historical background, pathogenesis, clinical presentation, and self-limited course of this common, yet frequently unrecognized illness are discussed. PMID- 1610048 TI - Klippel-Feil syndrome. AB - Klippel-Feil syndrome is characterized by congenital fusion of two or more cervical vertebrae and may be associated with other organ system anomalies. Although many congenital anomalies are of little clinical importance to the emergency physician, Klippel-Feil syndrome is associated with both spontaneous and progressive neurologic sequelae as well as a predisposition for serious neurologic injury after relatively minor neck trauma. Such patterns of skeletal abnormalities as an unstable fusion pattern, craniocervical anomalies, and associated spinal stenosis are associated with a higher risk of neurologic sequelae. We report the case of a patient with a previously undiagnosed type II Klippel-Feil syndrome who presented after neck trauma to illustrate how further diagnostic imaging modalities may be required to elucidate the presence or absence of acute injury. Key considerations in the emergency management of such patients include radiographic evaluation for hypermobile cervical segments, the anticipation of difficult tracheal intubation, and proper follow-up and referral because of the associated other organ system anomalies and progression of the skeletal pathology. PMID- 1610049 TI - Tropical pyomyositis in a temperate climate in an immunocompetent adult. AB - Tropical pyomyositis, though common in Africa, South America, and the South Pacific, is relatively rare in North America. Reported is the case of a patient who developed chest wall muscle abscesses after sustaining minor chest wall muscle trauma and presented to the emergency department appearing acutely ill. He was treated surgically with irrigation and debridement of the abscesses as well as with antibiotics and recovered fully over a seven-month course. This case illustrates important aspects of tropical pyomyositis with a discussion of the natural history of this disease as well as diagnostic modalities and treatment options for this virulent infectious process that is usually caused by penicillin resistant Staphylococcus aureus. PMID- 1610051 TI - Incorrectly interpreted as normal? PMID- 1610050 TI - Painless abruptio placentae associated with disseminated intravascular coagulation and syncope. AB - Abruptio placentae is a complication of pregnancy associated with significant morbidity and mortality for both fetus and mother. The presence of uterine pain and tenderness traditionally has been considered a useful criterion for distinguishing abruptio placentae from other causes of bleeding in pregnancy. We report the case of a 25-year-old woman who presented with painless abruptio placentae and coagulopathy during the second trimester. This case illustrates the importance of considering this diagnosis in pregnant patients with vaginal bleeding. PMID- 1610052 TI - Is activated charcoal useful for acetaminophen overdose beyond two hours after ingestion? PMID- 1610053 TI - ER nurses respond to aftermath of LA rioting. PMID- 1610055 TI - SNA bargaining empowers RNs. PMID- 1610054 TI - Nurse execs exert power, influence. Interview by Mandy Mikulencak. PMID- 1610056 TI - A day in the life of a nurse. Perioperative RN is prepared. PMID- 1610057 TI - Lawsuit demands coping skills. PMID- 1610058 TI - Hall of Fame adorns new headquarters. PMID- 1610059 TI - Nursing needed to combat TB. As I see it. PMID- 1610060 TI - Together we can change it. PMID- 1610061 TI - Beyond pride. PMID- 1610062 TI - Labyrinthine enhancement on gadolinium-enhanced magnetic resonance imaging in sudden deafness and vertigo: correlation with audiologic and electronystagmographic studies. AB - Sudden deafness with or without vertigo presents a difficult diagnostic problem. This article describes 12 patients with enhancement of the cochlea and/or vestibule on gadolinium-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (MRI), correlating the enhancement with the auditory and vestibular function. All patients were studied with T2-weighted axial images taken through the whole brain, enhanced 3-mm axial T1-weighted images taken through the temporal bone, and enhanced T1-weighted sagittal images taken through the whole brain. Cochlear enhancement on the side of hearing loss was found in all the patients. The vestibular enhancement correlated with both subjective vestibular symptoms and objective measures of vestibular function on electronystagmography. In 2 patients, the resolution of symptoms 4 to 6 months later correlated with resolution of the enhancement on MRI. No labyrinthine enhancement was seen in a series of 30 control patients studied with the same MRI protocol. Labyrinthine enhancement in patients with auditory and vestibular symptoms is a new finding and is indicative of labyrinthine disease. While abnormalities on electronystagmograms and audiograms are nonspecific and only indicate a sensorineural problem, enhanced MRI may separate patients with retrocochlear lesions, such as acoustic neuromas, from those in whom the abnormal process is in the labyrinth or the brain. PMID- 1610063 TI - Pediatric airway reconstruction at Great Ormond Street: a ten-year review. I. Laryngotracheoplasty and laryngotracheal reconstruction. AB - One hundred eight consecutive patients with pediatric laryngotracheal stenosis requiring airway reconstruction over a 10-year period were reviewed. One hundred forty-nine operations consisting of 75 laryngotracheoplasties and 74 laryngotracheal reconstructions with costal cartilage grafting were performed. The Cotton grading scheme of preoperative stenosis was useful in predicting likelihood of decannulation. In all, 90 patients (83%) were decannulated. PMID- 1610064 TI - Otolaryngologic manifestations of the mucopolysaccharidoses. AB - A retrospective review of 45 children with mucopolysaccharidoses was performed to determine the frequency of complications related to the head and neck. In this series, every patient had at least one complication involving the head and neck region, and in over half, operative intervention by the otolaryngologist was required. Upper airway obstruction occurred in 17 (38%) and necessitated a tracheostomy in 7 (16%). Cervical spine instability occurred in 8 (18%), making airway management difficult. Recurrent respiratory infections occurred in 17 (38%), and chronic recurrent middle ear effusions were noted in 33 (73%). This review demonstrates that children afflicted with the mucopolysaccharidoses frequently have otolaryngologic-related complications that are common throughout their life span and often the primary management issue in their continuing care. The otolaryngologic management of these patients is outlined based on the results of this study and review of the relevant literature. PMID- 1610065 TI - Presence of an 80 kilodalton protein, cross-reacted with monoclonal antibodies to pulmonary surfactant protein A, in the human middle ear. AB - We report the presence of a middle ear protein that has the same epitope as human surfactant protein A. Monoclonal antibodies (PC-6 and PE-10) against human pulmonary surfactant protein A stained faint granules of the mucosal epithelial cell cytoplasm in the orifice of the eustachian tube immunohistochemically. These antibodies also reacted with middle ear effusion of patients with otitis media with effusion by dot immunoassay, and recognized an 80 kd protein by Western blot analysis. These findings indicate that a protein immunoreactive with PC-6 and PE 10 occurs in the mucosal epithelial cells of the middle ear, and is also present in middle ear effusion. It is therefore likely that this 80 kd protein might be secreted from the mucosal epithelial cells to the middle ear cavity. PMID- 1610066 TI - Interpretation of electrocochleography in Meniere's disease and normal subjects. AB - Electrocochleographic recordings were obtained from 20 subjects with normal hearing and 10 subjects with Meniere's disease by using an eardrum electrode. Stimuli included clicks and 6,000-Hz tone bursts. Results were not significantly different between the two groups for summating potential (SP) amplitude, action potential (AP) amplitude, or the SP/AP amplitude ratio. Interpreting the results in light of symptoms on the date of assessment or hearing threshold did not appear to improve separation between the two groups. Various SP/AP amplitude ratio criteria have been proposed in order to separate normal patients from those with Meniere's disease. Applying these proposed criteria to our data did not successfully separate the two groups. PMID- 1610067 TI - Pull-through branchial fistulectomy: a technique for the otolaryngologist. AB - The complete second branchial fistula consists of a superficial infrahyoid portion and a deep parapharyngeal portion. Through the present technique, the infrahyoid portion is dissected from the neck while the parapharyngeal segment is dissected through the mouth with or without tonsillectomy. Eventually, the whole fistula is pulled out through the mouth. This technique ensures complete fistulectomy and a low recurrence rate, is more cosmetic than the traditional technique, and allows simultaneous tonsillectomy. It may not be satisfactory if the fistula was the seat of repeated infections. This technique is suitable for the otolaryngologist, who is naturally well acquainted with microsurgery and tonsillectomy. PMID- 1610068 TI - Communication status following laryngectomy: the Iowa experience 1984-1987. AB - Data regarding treatment and outcome for a consecutive series of 73 total laryngectomy patients were collected from clinical records with a follow-up period of 30 to 78 months postoperatively. Notable findings were that 27% were women; 75% reported hoarseness or a voice change as an early symptom; and 22% reported combined heavy use of both cigarettes and alcohol. Of the 73 patients, 38 (52%) died during the follow-up period; 18 of the 38 died within 1 year postoperatively. Thirty-nine (53%) of the 73 had received a surgical tracheoesophageal fistula (TEF) for voice restoration, as either a primary or a secondary procedure. Of the 39, 75% were using the TEF at last examination, with no failures attributed to sphincter spasm. Of the total group, the primary communication modality was reported to be use of a TEF by 44% and use of an electrolarynx by 50%. Limitations of the study and directions for future investigations are discussed. PMID- 1610069 TI - Rapid voice tremor, or "flutter," in amyotrophic lateral sclerosis. AB - In an attempt to clarify the origin and frequency characteristics of a rapid voice tremor, or "flutter," in patients with amyotrophic lateral sclerosis (ALS), eight patients (four men and four women; ages 42 to 70 years) who had ALS and rapid voice tremor and an age- and sex-matched control group of eight subjects were asked to sustain the vowel /a/ and their voices were recorded for later analysis. Each segment of phonation was demodulated into amplitude and frequency components. From each subject's 8-second amplitude and frequency signals, a fast Fourier transform analysis was done on a 1-second segment previously identified perceptually as having the most apparent tremor or flutter. The results showed that patients with ALS had multiple combinations of levels and frequencies for amplitude and frequency modulations in comparison with control subjects, who had consistently low levels of modulations. In an attempt to quantify the tremor or flutter in ALS, amplitude and frequency modulations were not clearly or predominantly represented at one point along the spectrum. Nevertheless, these frequency and amplitude modulations are more prominent in patients with ALS than in normal subjects. The origins of these aberrant frequency and amplitude modulations in ALS patients remain obscure, although speculation is that they are of peripheral rather than central nervous system origin. PMID- 1610070 TI - Heterogeneity in epidermal growth factor responsiveness and tumor growth of human maxillary cancer cell lines. AB - We have established three cell lines (IMC-2, IMC-3, and IMC-4) from a human maxillary tumor, which exhibited different sensitivities to epidermal growth factor (EGF). It was inhibitory to colony-forming abilities of IMC-3 and IMC-4 cells in culture, while it affected that of IMC-2 cells slightly if at all. The differential sensitivities to EGF among the three cell lines were reproducibly observed when several cell sublines were further established from tumors appearing in nude mice. Saturation-binding kinetics with 125I-EGF showed similar levels of EGF-binding activities among the three cell lines. However, IMC-2, IMC 3, and IMC-4 showed almost similar sensitivities to cisplatin. Autophosphorylation of EGF receptor in the presence of EGF proceeded at similar levels among the three cell lines. Tumor growth was followed in nude mice when IMC-2, IMC-3, and IMC-4 at 1 x 10(7) cells were inoculated. The IMC-2 tumors enlarged at much faster rates than the other two cell lines. The IMC-4 tumors showed very slow growth rates, and IMC-3 tumors enlarged at an intermediate rate. These data suggest that the maxillary tumor used comprised cell populations that differed in their growth behaviors in response to EGF. PMID- 1610071 TI - Vestibulo-ocular compensation following unilateral vestibular deafferentation. AB - Vestibulo-ocular compensation following vestibular deafferentation was investigated in 26 acoustic neuroma patients following tumor removal and in 5 Meniere's disease patients following vestibular nerve section by using sinusoidal harmonic acceleration testing. All three test parameters (phase lead, gain, and asymmetry), when averaged, shifted significantly on the first postoperative test (average 0.4 months after operation). A marked progression in central compensation with gain returning to the range of normal control values was seen in the tests performed 1 to 6 months (average 2.6 months) postoperatively. However, phase lead and asymmetry (especially at 0.01, 0.02, 0.04, and 0.08 Hz) remained outside the range of normal control values, and all three parameters failed to return to their preoperative level even when tested at more than 12 months (average 20.2 months) after operation. This finding indicates that the deficits of the vestibulo-ocular reflex to head acceleration are of long duration if not permanent. PMID- 1610072 TI - Reading skills and auditory processing ability in children with chronic otitis media in early childhood. AB - The effect of recurrent middle ear disease during the first 2 years of life on auditory perceptual skills and reading ability was examined in two groups of 6- and 7-year-old children who were pair-matched by age, gender, socioeconomic status, and receptive vocabulary. Group 1 consisted of children with documented chronic otitis media at an early age, and group 2 had no history of middle ear problems. Tests of auditory perceptual skills and reading ability were administered. Significant differences in performance on all tests of auditory processing ability and reading ability were noted. PMID- 1610073 TI - Rounded atelectasis. PMID- 1610074 TI - [Experimental paratuberculosis in sheep after intravenous or oral inoculation: pathogenicity and biologic diagnosis]. AB - An experimental paratuberculosis study was performed in sheep. One group of 6 lambs was inoculated intravenously with the equivalent of 50 mg (wet weight) of live bacilli, another group of 6 lambs was inoculated orally by placing 500 mg (wet weight) of live organisms in milk feed and a group of 3 lambs was used as controls. The degree of cellular immunity was followed by examining delayed hypersensitivity using 3 allergens (bovine tuberculin PPD, avian tuberculin PPD and johnine PPD) and that of humoral immunity using complement fixation test, agar gel immunodiffusion test and ELISA. The elimination of bacilli in the faeces was examined simultaneously. After 2 years no macroscopic or microscopic lesion was observed in intravenously inoculated lambs and in those exposed orally to M paratuberculosis; cultures were negative. It appears that domestic sheep were able to control the infection. Nevertheless, most of them developed cellular and humoral immunity against paratuberculosis antigen. The best results were obtained in intravenously inoculated lambs. PMID- 1610075 TI - Vitamin E kinetics after intraperitoneal administration of DL-alpha-tocopherol and DL-alpha-tocopherol acetate in sheep. AB - The disposition of radiotocopherol after intraperitoneal administration of 14C labelled-DL-alpha-tocopherol (1 microCi/kg bw, dose 1) and 3H-labelled-DL-alpha tocopherol (4 microCi/kg bw dose 4) and of D-alpha-tocopherol, after intraperitoneal administration of DL-alpha-tocopherol acetate (100 mg/kg bw) was investigated in sheep. Plasma samples were taken at regular intervals after dosing and assayed for radioactivity and D-alpha-tocopherol. Plasma profiles were modelized using a compartmental approach and the input entry rate (for radioactivity) was identified using a numerical deconvolution method. Based on plasma specific activity (dose 1 and dose 4) and D-alpha-tocopherol plasma concentration (unlabelled alpha-tocopherol acetate), half-lives were not significantly different (99.6 +/- 28.3 h, 121.3 +/- 38.5 h and 75.0 +/- 49.75 h after dose 1, dose 4 and unlabelled alpha-tocopherol respectively). The times to reach maximal plasma concentrations were similar for the 3 test articles (mean values ranging from 21.5 to 26.7 h). The only significant difference was observed for the apparent volume of distribution (with respect to bioavailability) which was much larger for the unlabelled test article. Deconvolution study of plasma specific activity showed: i), that the maximal input rate was reached only after a short delay (3 to 12 h); ii), that half of the activity was absorbed after a delay of 38.13 +/- 16.76 h (dose 1) and 44.3 +/- 6.50 h (dose 4); and iii), that 90% of the activity was absorbed after 151.2 +/- 27.3 h (dose 1) and 162.3 +/- 11.2 (dose 4). It is concluded that the intraperitoneal route is of interest for alpha-tocopherol administration, but that more information is required to determine the exact process of absorption. PMID- 1610076 TI - [Content of nitrate in milk. Relationship with its concentration in the water supply for livestock]. AB - Environmental pollution leads to increasing nitrate levels in dairy cattle's water supply. Possible repercussions regarding nitrate content in milk should therefore be considered. The results are presented of nitrate dosage in milk collected from cows provided with drinking water containing 0-180 mg/l nitrate. They show that drinking water has no significant effect on milk nitrate content which remains very low. It is concluded that this product does not constitute a health risk to consumers. PMID- 1610077 TI - Effect of vitamin E supplementation and of health status of mammary gland on immunoglobulin concentration in milk of dairy cows. AB - Variation of milk IgG1, IgG2, IgM, and IgA measured by radial immunodiffusion was studied in monthly samples of 224 lactating dairy cows. Cows were assigned to one of 2 treatment groups: vitamin E supplemented and controls. Vitamin E supplementation was started when cows were dried and continued until 90 days post partum at the rate of 1,000 IU per cow daily and then reduced to 500 IU for the remaining lactation. There were no significant differences between the 2 treatment groups for the different Ig classes. Concentrations of IgG1 were significantly higher in milk from mastitic than non-mastitic cows. PMID- 1610078 TI - Influence of the stage of pregnancy on gentamicin disposition in the ewe. AB - The influence of the state of pregnancy (mid- and end of pregnancy) on the kinetic disposition of gentamicin was determined in the ewe. Kinetic parameters were determined after a single intravenous bolus administration (4 mg/kg). It was shown that the steady state volume of distribution was significantly increased from mid to end of pregnancy (from 0.09 I.kg-1 to 0.194 I.kg-1). Similarly, plasma clearance was increased by about 150% at the end of pregnancy. These modifications must be taken into account in order to adapt the dosage regimen and determine a withdrawal time for gentamicin. PMID- 1610079 TI - [Actinomyces pyogenes: conventional and Api system bacteriologic study of 103 strains isolated from ruminants]. AB - One hundred and three strains of Actinomyces pyogenes isolated from ruminants were examined for morphological, cultural and biochemical properties by standard tests and by the Api 50 CH and Api Coryne methods. No biotype could be demonstrated, but a few atypical non- or practically non-proteolytic strains were detected which should be differentiated from Arcanobacterium haemolyticum. Criteria for laboratory identification of A pyogenes were established: Gram stain; culture on blood agar; deep agar and Loeffler's medium; catalase, nitrate reduction, acid formation from xylose; Hugh and Leifson test. The Api Coryne system correctly identified only 58 of 103 A pyogenes cultures, which implies that it should be re-evaluated before use in veterinary diagnosis laboratories. PMID- 1610080 TI - Conjunctival vaccination of pregnant ewes and goats with Brucella melitensis Rev 1 vaccine: safety and serological responses. AB - When Brucella melitensis strain Rev 1 vaccine (Rev 1) is administered by the standard method (1-2 x 10(9) viable bacteria injected subcutaneously), it may induce long-lasting serological responses and/or cause abortion in pregnant animals. The conjunctival route considerably reduces these drawbacks. In the present experiment a 1 x 10(8) CFU dose for both ewes and goats conjunctivally vaccinated at mid-pregnancy was tested for innocuousness (outcome of pregnancy, contamination of unvaccinated contact animals, duration of serological responses) in comparison with 3 x 10(8) CFU (ewes and goats), 1 x 10(9) and 3 x 10(9) CFU (ewes) doses. No reaction was observed at the time of vaccination, and the risk of environmental contamination with Rev 1, due to the conjunctival administration of the vaccine, is negligible. Abortions occurred later at surprisingly severe rates (over 60% of pregnant vaccinated animals), except in the 1 x 10(8) CFU ewes group (20%). Moreover, the serological reactions of the 1 x 10(8) CFU ewes which normally lambed were negative again as early as 12 weeks after vaccination. Although the dose of 1 x 10(8) CFU Rev 1 was safer for pregnancy than the standard dose mainly in ewes as compared to goats, the innocuousness was not yet sufficient to propose the former dose to indiscriminately vaccinate sheep and goats by the conjunctival route, whatever the age or physiological status. PMID- 1610081 TI - [Lentivirus expression at the moment of lambing modifies the leukocyte number in the milk of multiparous ewes]. AB - Lambing in small ruminants is a time of high lentivirus expression; infected mononuclear phagocytes are frequent in colostrum and milk. We have studied mammary secretions in 5 multiparous ewes and shown that infected macrophages in milk are accompanied by an augmentation of leucocyte number. The lymphocyte CD8 subpopulation increased in size simultaneously with the onset of infected cell excretion. The udder infection by coagulase negative staphylococci did not modulate milk lymphocyte content. Although infected cell excretion was restricted to one half of the udder, virus-specific lesions were found in both udder halves. Milk leukocytes changes are a marker of infected macrophage presence; they do not control lentivirus spread. PMID- 1610082 TI - [Total pharyngolaryngoesophagectomy. Indications and results apropos of 17 cases]. AB - Pharyngolaryngoesophagectomy (PLO) allows one-stage treatment of synchronous tumors involving both esophagus and hypopharynx and may also be advocated when the pharyngo-esophageal junction (PEJ) is involved. Less radical surgery may be advocated in the case of hypopharyngeal malignancy sparing the pharyngoesophageal junction. The authors report the results of 17 PLO carried out in 11 cases for a tumor involving the PEJ, and in 4 cases for synchronous tumors involving esophagus and hypopharynx. In 2 instances, PLO was performed for primary hypopharyngeal malignancy requiring total circular excision (i.e. which did not involve the PEJ). Five patients had previously received chemotherapy and 6 had had an association of chemotherapy and radiation therapy as initial treatment before surgery. Reconstructive procedure used the stomach and colon in 12 and 5 cases respectively. Hospital mortality was 4 cases out of 17. There was 1 cervical fistula secondary to pharyngogastric anastomosis necrosis. One and 2 year actuarial survival rates were 73% and 37%. Tumor recurrence and a remote new tumor were noted in 6 and 4 cases respectively, despite extensive surgical procedures and the use of chemotherapy and/or radiotherapy. When esophagectomy was added to total circular excision in case of hypopharyngeal tumor sparing the PEJ, no significant benefit was noted. Good functional results obtained by means of PLO shall lead to therapeutic trials including surgery, chemotherapy and radiotherapy with the aim of improving long-term results. PMID- 1610083 TI - [Esophagectomy without thoracotomy for adenocarcinoma in Barrett's esophagus]. AB - From April 1985 to November 1990, 12 patients with adenocarcinoma in a Barrett's esophagus, all of them men, with a median age of 62 years (range, 46 to 79 years), were operated by transhiatal esophagectomy and were submitted to a periodic follow-up. Dysphagia was the main symptom. Preoperative investigations included esogastroscopy and CT-scan of the abdomen and thorax in all patients. Esophageal endosonography was performed in the last 4 cases and MRI in one case. All patients recovered postoperatively and were discharged from hospital. The resected specimens were staged according to Rosenberg et al.'s classification: stage 1, 3 patients, stage 2, 2 patients, stage 3, 6 patients, stage 4, 1 patient. An anastomotic stricture occurred in 4 patients and was treated successfully by endoscopic dilatation. Five patients died during the follow-up period. Seven patients are alive without evidence of recurrence. Transhiatal esophagectomy appears to be the procedure of choice for adenocarcinoma arising from Barrett's esophagus. PMID- 1610084 TI - [Anatomy of the caudate lobe of the liver. New aspects and surgical applications]. AB - The caudate lobe is the only real and constant hepatic lobe of mammals and it requires a better delimitation in a modern conception of human liver segmentation. Owing to its dorsal, central and low anatomical situation, this lobe is connected to many segments of the liver and its inflow and outflow vessels are complex and variable. The authors, who studied 242 human livers, describe the typical pattern of these vessels and their anatomical and numerical variants. By its portal branches the lobe seems to depend upon the left lobe of the liver and its arterial and portal inflow as well as its hepatic vein system are better than these of other segments of the liver; moreover this segment can be compared to a quadrangular pyramid which presents an external part, superficial with easy surgical access, and an internal part, deeper and very difficult to resect. It is possible to remove segment I of the liver without any other hepatic resections but, usually, a partial resection of the lobe is performed or a left lateral segmentectomy is required. In liver cancer, the invasion of the lobe generally means widespread tumor dissemination and its resection is not justified; on the contrary, the caudate lobe should be resected for radical operation in hilar cholangiocarcinoma. The tendency of the caudate lobe to overlap with the other 2 liver lobes and its very good inflow and outflow systems explain its ability to avoid postoperative hepatic failure because it can support the hepatic vein drainage and it has a considerable disposition to regenerate. PMID- 1610085 TI - [Conservative treatment for trauma of the spleen in adults. Comparative study of thirty-four cases of conservative treatment and sixty-one cases of splenectomy]. AB - Between 1983 and 1990, 95 patients with abdominal injury and splenic damage underwent surgery. Conservative treatment was performed in 34 cases (group I) and splenectomy was performed in 61 cases (group II). In group I, one patient died and post-operative complications occurred in 18 patients (53%). In group II, 3 patients died (of a 0hrenic abscess for one of them), and postoperative complications occurred in 38 patients (62%). There was no significant difference between group I and group II in terms of length of hospital stay and operation time; but a greater number of red cell concentrates was required during the operation in group II. No patient of group I developed post-operative infection during the mean interval of 18 months. This experience confirms that the conservative treatment of splenic contusions does not worsen the prognosis of abdominal injuries. Medium and long term infectious complications might be prevented by the conservative treatment but it is still too early to assess the real benefit of this option. PMID- 1610086 TI - [Celioscopic cholecystectomy in simple and complicated cholelithiasis. Apropos of 392 cases]. AB - In a study including 392 patients we compared two groups of patients according to the indication for laparoscopic cholecystectomy: group I: 293 patients treated for simple cholelithiasis (n = 291) or gallbladder polyps (n = 2). Group II: 99 patients operated for complicated cholelithiasis. For each patient, 14 pre, intra and postoperative parameters were analysed and compared. Mean operative time was 80 minutes. Primary and secondary laparotomies were necessary in 5.8% and 1.3% of cases respectively. Biliary injury was the most frequent complication (1.3%). Mean hospital stay was 4.5 days. In terms of mean age, operative time, intraoperative incidents and complications, and primary laparotomy. There was a significant difference between the two groups (p less than 0.001). There were 4 secondary laparotomies in group II and one in group I. These results suggests that laparoscopic cholecystectomy is a safe technique with a low mortality rate (0.25%). The comparative study proves that this technique, first indicated for simple cholelithiasis, is also applicable to the majority of complicated cholelithiasis. PMID- 1610087 TI - [Limited indications for posterior rectotomy. Results of a series of 42 cases]. AB - Forty-two mobile tumours on digital rectal examination were excised by posterior rectotomy: via a transsphincteric approach in 16 cases and via a pararectal suprasphincteric approach in 26 cases; 3 primary protective colostomies were performed. Nineteen tubulovillous adenomas and 23 carcinomas were excised. The excision included the entire thickness of the rectal wall in the form of resection-anastomosis (n = 10) or a disk resection (n = 32). This series consisted of 27 males and 15 females between the ages of 42 and 92 years (mean = 70 years). The definitive histology revealed 12 T1 tumours, 7 T2 tumours and 3 T3 tumours. There were two postoperative deaths. The remaining patients have a mean postoperative follow-up of 45 months. 2/16 (12.5%) local recurrences occurred in the group of tubulovillous adenomas and 2 local recurrences with distant metastases were observed in the carcinoma group, while 3 patients only developed distant metastases. The cancer-related mortality was 5/21 (23.89%). Disturbances of continence persisted in 6/29 surviving patients, 4 patients complained of urgent defecation, 1 of uncontrolled passage of gas and a single patient had persistent incontinence of liquid stools. Posterior rectotomy allows excision of extensive tubulovillous adenomas and local recurrences are less frequent than after transanal excision and are similar to the results obtained with transabdominal rectal resections. The operative mortality was lower than that of laparotomy. Posterior rectotomy allows adequate resection of localised carcinomas (T1) with no lymph node involvement. The statistical frequency of lymph node metastases in stage T2 and T3 tumours only justifies the use of this technique when the patient refuse colostomy, has an excessively high risk to undergo laparotomy or when the operation is purely designed to be palliative. The disturbances of continence observed were minor and only slightly disabling. PMID- 1610088 TI - [Primary colonic intussusception protruding from the anus in adults. Two cases]. AB - The authors report two cases of colonic intussusception in the adult protruding from the anus--or colo-anal intussusception--, not due to a tumor. The first case was a chronic ileo-caeco-colique intussusception, the second case was an acute colo-rectal intussusception. Colo-anal intussusceptions are very rare: less than twenty cases have been described since 1925 in adults. The absence of a tumor origin in our cases represents a special feature, as only three other similar cases have been described. The surgical treatment in both cases was primary colonic resection without colostomy. The surgical treatment of the first case was subtotal colectomy with ileo-rectal anastomosis. The second case was primarily reduced by barium enema which allowed optimal secondary surgical resection of a prepared colon. PMID- 1610089 TI - [Heller's operation in the treatment of idiopathic megaesophagus. Apropos of 25 cases]. AB - The authors report 25 cases of idiopathic mega-oesophagus treated by Heller's myotomy via an abdominal incision with prevention of gastro-oesophageal reflux by means of Toupet, Dor or Nissen procedures. The results, with a follow-up of 2 to 13 years, were considered to be good in 82% of cases with 2 moderate results (9%) and two failures (9%). The authors consider Heller's operation to be the operation of choice in preference to forced dilatations. PMID- 1610090 TI - [Fractures of the distal radius with posterior displacement. Kapandji's technique]. PMID- 1610091 TI - [Cystic lymphangiomas of the pancreas. Three new cases]. AB - Cystic lymphangiomas are vascular dysembryoplastic lesions. Three pancreatic cases are reported. Preoperative diagnosis is rarely possible and laparotomy is mandatory. Complete resection prevents recurrence but excessively aggressive surgery is not required for this benign disease. PMID- 1610092 TI - [Myocardial radionuclide tomography using Thallium 201 and detection of coronary re-stenosis after single-vessel angioplasty]. AB - Among non-invasive methods for the detection of coronary restenosis after successful transluminal coronary angioplasty, the contribution of exercise myocardial Thallium 201 tomoscintigraphy (MTS) was assessed in a prospective study involving 168 patients with a mean age of 56 (range 32-75) who had undergone 174 successful single vessel angioplasties (86 AIV, 35 Cx, 53 RC) with residual stenosis of 50% or less. After an interval of 6 +/- 2 months, patients were reassessed without treatment by a maximum exercise test (ET) combined with Thallium 201 MTS, 24 hours before follow-up coronary arteriography. Restenosis, defined by a greater than 50% loss of the gain achieved by the initial angioplasty, was seen in 53 patients (30.4%). MTS, with the exception of any necrosed area, was read as positive in case of reversible exercise hypofixation with redistribution. Sixty seven tests were positive, 49 corresponding with restenosis. Four were normal despite restenosis. The diagnostic values of the 3 methods of angina, ET and MTS were 0.43, 0.74 and 0.92 respectively for sensitivity, 0.89, 0.85 and 0.85 for specificity, 0.64, 0.68 and 0.73 for positive predictive value and 0.78, 0.88 and 0.96 for negative predictive value. In total, MTS at 6 months had the best sensitivity for the detection of coronary restenosis after single vessel angioplasty and an excellent negative predictive value (96% alone, 100% combined with ET), eliminating the need for coronary arteriography when it is negative. PMID- 1610093 TI - [Experimental study of fulguration of healthy ventricle. II. Chronic lesions]. AB - The effect of fulguration shocks was studied using healthy ventricular myocardium of 12 pigs weighing between 63 and 100 kg. With shocks of equal energy to those used clinically, lesions seen 24 hours after the session in two pigs showed the formation of loose fibrosis and of marked cellular infiltration as well as zones of hypercontraction with calcium precipitation. The size of chronic lesions seen during periods ranging from one week to 2 months was studied in 4 pigs. Transmural plaques with a diameter of 1.5 to 2 cm were seen in the right ventricle. For the same energy levels of 240 Joules delivered to left ventricular tissue, lesions were of the same size but were never transmural. Under certain conditions, lesions were disposed in the direction of the neutral electrode. PMID- 1610094 TI - [Vascular complications in infectious endocarditis. Apropos of 86 cases]. AB - During a 20 year period, 285 patients were hospitalised for infectious endocarditis (IE) in the Department of Cardiology of the Ernest-Conseil Hospital in Tunis and 86 of them, i.e. 30%, developed a vascular complication (VC). Among these 86 patients, there were a total of 108 lesions, including 52 neurological complications, 14 peripheral acute ischemic syndromes, 16 peripheral arterial aneurysms, 9 aortic aneurysms, 7 pulmonary embolisms, 6 splenic infarctions and 4 coronary lesions. The mortality in this patient group proved to be slightly greater than in the series as a whole, in particular concerning patients with multiple lesions and those with an artificial valve. No prognostic difference was seen between patients with a VC of aneurysmal type and of ischemic type, but the presentation and severity of lesions was very variable. The vascular complication was a presenting feature of IE in almost 40% of cases. The organism found most often was the streptococcus, above all in ischemic type IE as well as in the total patient group. Similarly, the preferential site was aortic, above all for aneurysmal type IE. Ultrasonography revealed a higher incidence of vegetations in this series of patients, above all in ischemic type VC, but anatomical studies have shown this to be an investigation of moderate sensitivity and poor specificity, poorly correlated from a prognostic standpoint with the risk of embolism. The conclusion of the study is above all the need to prevent such complications: embolic complications by early antibiotic treatment and valve replacement and aneurysmal complications by methodical routine angiographic evaluation and appropriate treatment. PMID- 1610095 TI - [Cerebral embolism disclosing a left intraventricular thrombus 6 years after atypical infarction]. AB - The authors report a case which is unusual because of the late presentation, as a cerebral embolism, of a left intraventricular thrombus six years after an infarction. This thrombus was absent at the acute stage of the infarction. The conditions surrounding the development of a thrombus after an infarction are reviewed. This is a common complication at the acute stage of an anterior infarction, notably when there is apical akinesia. The late onset of these thrombi has not been extensively studied in the literature. This would appear to be a fairly rare event but which, as shown by our case, pleads in favour of very prolonged anticoagulant treatment after certain myocardial infarctions. PMID- 1610096 TI - [Myocardial infarction and coronary artery aneurysm]. AB - Two cases of aneurysm of the right coronary artery are reported. These atheromatous aneurysms not associated with tight coronary stenosis were responsible for myocardial infarctions treated by early intravenous thrombolysis with a resultant limited area of necrosis. According to the literature, coronary aneurysms associated with stenosis are not rare. Aneurysms not associated with significant stenosis appear to be much less common and the prognosis of patients with such lesions would not seem to be worse than that of those with neither aneurysm nor significant coronary stenosis. From a pathophysiological standpoint, the development of local thrombosis appears to play a determinant role in terms of the clinical manifestation of these aneurysms and its prevention justifies the long term combined prescription of platelet antiaggregants and oral anticoagulants. PMID- 1610097 TI - [Cardiovascular risk after menopause]. AB - It is highly probable that the menopause, spontaneous or above all artificially induced, is a cardiovascular risk factor. However, it is less important than other conditions (hypertension, smoking, obesity, diabetes, hypercholesterolemia) with which it is often associated and which it may favourise or worsen. In this respect, hormone replacement therapy is probably beneficial, probably by an action on the arterial endothelium itself, and certainly by opposing the factors which favourise the development of atheroma (metabolic and hemostasis disorders). Its aims and techniques, and hence its cardiovascular consequences, are very different from those of hormonal contraception, with which it must neither be compared nor confused. It would be reasonable, on the basis of these advantages, to extend the indications of post-menopausal hormone replacement therapy to an increasing number of women and for a longer period. PMID- 1610098 TI - [Preventive treatment of systemic embolic complications of atrial fibrillation]. AB - Non-valvular atrial fibrillation multiplies the risk of presumed embolic events by a factor of four. The hemorrhagic risk of anticoagulant treatment varies considerably and its prophylactic efficacy was not tested in any randomised trial before the end of 1989. The recommendations of experts at that time recognised that data were inadequate. The publication since of four randomised trials involving 3,049 patients has provided a more objective base for management decisions, highly in favour of the anticoagulation of cases of non-isolated atrial fibrillation in the absence of contraindications. PMID- 1610099 TI - [Coronary disease and peripheral arterial disease: contribution of echo-Doppler in the study of the arteries of the neck and lower limbs before the age of 60. Apropos of 76 cases]. AB - Echo-duplex exploration of heart and inferior limbs arteries is performed in 76 patients less than 60 years old, with angiographically established coronary heart disease. Peripheral vascular lesions are found in 15 cases (20%), they are more frequent in patients with tritrunkular coronary disease (35%) than in those with one (16%) or two-vessel lesions (10%). Mean encephalic circulatory resistance index is higher in patients with tritrunkular lesions (p less than 0.03). Vascular echo-duplex should be performed in case of coronary disease in order to avoid catheterism complications and to purpose combined surgical procedure (coronary bypass and carotid endarterectomy). PMID- 1610100 TI - Analytical reviews in clinical biochemistry: the estimation of urea. PMID- 1610101 TI - Immunoglobulin G, A and M light chain ratio in children. AB - Values for the kappa/lambda light chain ratio in immunoglobulins G, A and M and the total kappa/lambda ratio, measured by enzyme linked immunosorbent assay, were evaluated in serum samples from different age groups (114 children, aged from 1 month to 15 years, and 20 adults). The IgG kappa/lambda ratio decreased in the first 6 months and subsequently increased slowly during childhood towards the adult value of 2.0. The IgM kappa/lambda ratio increased at a greater rate than IgG kappa/lambda ratio in the first years of life and thereafter rose slightly throughout childhood to reach an adult value of 1.7. A decreasing IgA kappa/lambda ratio was found from 1 month of age onwards to an adult value of 1.1. The pattern of total kappa/lambda ratio was similar to the IgG kappa/lambda ratio with an adult value of 2.0. PMID- 1610102 TI - Direct measurement of low density lipoprotein in whole blood by silver-enhanced gold-labelled immunoassay. AB - A competitive silver-enhanced gold-labelled immunoassay has been developed for the direct measurement of low density lipoprotein (LDL) in whole blood. Immobilized LDL and sample LDL compete for added antibody. Quantitation of the bound antibody/antigen complex is achieved by the addition of gold-labelled anti immunoglobulin G followed by enhancement of absorbance by addition of silver ions. Whole-blood samples from fasting patients were assayed directly for LDL by the procedure and the corresponding plasma samples were assayed for total cholesterol, high density lipoprotein and triglycerides followed by the indirect calculation of LDL cholesterol. The correlation between the two methods was good (r = 0.82) and the SEGLISA exhibited good precision. PMID- 1610103 TI - Triglyceride fatty acid chain length influences the post prandial rise in serum intestinal alkaline phosphatase activity. AB - Intestinal alkaline phosphatase (IALP) activity rises following the ingestion of a fat-containing meal. Previous studies on intestinal fluid and lymph have shown that the magnitude of this response is dependent upon fatty acid chain length. To examine this relation in the serum of healthy humans, 10 subjects consumed two standardized fat meals. One meal contained predominantly long chain fatty acid triglycerides, the other contained predominantly medium chain fatty acid triglycerides. Serum IALP activity was measured in serial blood samples using a sensitive immunological assay. IALP activity was ABO blood group and secretor status dependent. The post-prandial rise in serum IALP activity was significantly greater following the long chain fatty acid meal than following the medium chain fatty acid meal. Previous observations of the fatty acid chain length dependency of the IALP response to fat ingestion, therefore, also apply in the serum of healthy humans under normal physiological conditions. Standardized fat meals provide the basis of a useful method for the investigation of the role of IALP in fat absorption. PMID- 1610104 TI - Assay of N-acetyl-beta-D-glucosaminidase in urine from neonates: comparison of two new colorimetric methods using MNP-GlcNAc and VRA-GlcNAc as substrates. AB - The NAG activity present in urine from newborn babies was assayed using two colorimetric procedures with either MNP-GlcNAc or VRA-GlcNAc as substrate and compared with data obtained with the well established PNP-GlcNAc procedure. Both new assays were easy to perform and reproducible. The MNP-GlcNAc method has the advantage that it is now available as a kit; however, the VRA-GlcNAc procedure is more sensitive. NAG activity, creatinine concentration and NAG-index values were determined in normal neonates and within-run imprecision calculated. Excellent correlations were found between MNP-GlcNAc-ase and VRA-GlcNAc-ase indices (r = 0.984) and between PNP-GlcNAc-ase and VRA-GlcNAc-ase indices (r = 0.952). When low molecular weight urinary components were removed by gel filtration no significant change in VRA-GlcNAc-ase activity was observed. PMID- 1610105 TI - Evaluation of capillaries for ionized calcium measurements. AB - Commercially available capillaries containing calcium-titrated heparinate as an anticoagulant designed specifically for ionized calcium measurements in blood were tested with four serum pools with ionized calcium concentrations adjusted to 0.75, 1.25, 1.50 and 2.50 mmol/L. Although this is the best available anticoagulant for this purpose, the use of these capillaries induced a +/- 1% alteration of the original concentration around the titration level and changes of -2 to +10% at pathological values. The amount of heparinate released exceeded the recommended limit of 50 IU/mL of specimen with some variability (6% to 20%). Increasing the amount of anticoagulant with the objective of avoiding magnetic mixing did not seem to be a valid approach. Finally, Radiometer, IL and AVL capillaries gave the best available and acceptable results in terms of alterations in ionized calcium. PMID- 1610106 TI - Plasma creatinine and the effect of delay in separation of samples. AB - There is a prevailing opinion that creatinine is an analyte which may be assayed with confidence in the plasma of ageing whole-blood samples. This is true of continuous flow methods employing dialysis, but in this study, where creatinine was measured in old samples by a kinetic Jaffe method on a discrete analyser, the concentration of creatinine was falsely raised. When plasma was left in contact with cells for 48 h, there was an apparent rise in the plasma creatinine by over 100 mumol/L compared with the 2 h concentration. This method-dependent error is therefore clinically significant. PMID- 1610107 TI - External quality assessment of Jordanian clinical chemistry laboratories. AB - A two-year study using inter-laboratory surveys has been carried out to assess the analytical quality of Jordanian clinical chemistry laboratories. The study surveyed greater than 65% (60 laboratories) of Jordanian laboratories using 18 control specimens and covering a total of 15 analytes. Close agreement was obtained between the consensus values and the designated values for analytes which had mean values within the normal range, whereas significantly lower consensus values were obtained for glucose, creatinine, bilirubin and urea in the pathological range. Considerable interlaboratory variation was observed in Jordan relative to EQA schemes in other countries. This study highlighted several problems in Jordanian laboratories, and stressed the need for a national EQA scheme with an effective means of providing continuous advice, education and training in clinical chemistry. PMID- 1610108 TI - Measure of satisfaction of general practitioners with the chemical pathology services in Leeds Western Health District. AB - The satisfaction of general practitioners with the District Chemical Pathology Services in Leeds Western Health District was assessed by means of a postal questionnaire. The areas of interest covered included communication, test turn round times, format of reports, advice about tests undertaken in the practice and chemical pathology information services. Communication with the laboratory was the major area of dissatisfaction (21% GPs), followed by test turn-round times (14%) and format of reports (10%). More than half the respondents were interested in an offer of help in selecting equipment for their surgeries and subsequent quality control. Customer satisfaction will become an important issue as a result of the NHS reforms and laboratories may find this exercise useful. PMID- 1610109 TI - Effects of using alternative antibodies in commercial non-separation enzyme immunoassays for drugs. PMID- 1610110 TI - Improving the performance of the ISE system on the Hitachi 737. PMID- 1610111 TI - Interference of dipyridamole in the analysis of porphyrins by HPLC. PMID- 1610112 TI - Discrepancies in hFSH measurements by two-site IRMA in the ovulatory phase of the menstrual cycle. PMID- 1610113 TI - Hypercalcaemia secondary to secretion of parathyroid hormone related protein from a somatostatinoma of the pancreas. PMID- 1610114 TI - Normal catecholamine production in a patient with a paroxysmally secreting phaeochromocytoma. PMID- 1610115 TI - [Familial Alzheimer's disease in France: results of a preliminary survey]. AB - This study concerns French families with Alzheimer's disease (13 families, with 37 diseased individuals). The incidence of female patients is higher than that of males. Variance of the age of onset is less important for intra-familial than inter-familial cases. The mean duration of the disease is shorter for early onset forms. One of these families was retained for molecular genetics studies. PMID- 1610116 TI - BrdU related direct revelation of typical dynamic R- and G-banding with the use of monoclonal anti-BrdU antibody. AB - Pulse 5-bromodeoxyuridine (5-BrdU) incorporation during the last S-phase is known to produce R- or G-banded chromosomes after photolysis-plus-Giemsa (FPG) staining. The authors applied an immunological staining with monoclonal anti-BrdU antibody instead of the FPG protocol. The results offered banded chromosomes with an immunological typical R-banding (RBI) on the GBG cultivated cells (early pulse incorporation), and an immunological G-banding (GBI) on the RBG cultivated ones (late pulse incorporation). After a further FPG protocol following an immunological treatment, an inverted banding pattern became evident whereas a faint immunological staining remained. Thus the method superimposed a GBG-banding on the RBI-staining or a RBG on the GBI one. This allows a rapid and easy R and G double chromosomal identification on the same metaphase cell, using first the immunological banding then the classical FPG staining. The method allows a reproducible dynamic G-banding with an easy monitored late 5-BrdU pulse incorporation specially attractive in spontaneous dividing cells from bone marrow. This dynamic G-banding protocol should be extended to chorionic villi and malignant cells. Our data are in agreement with a connection between dynamic banding and chromosomal portions containing or not BrdU. The lack of an immunological staining after the FPG protocol has been noticed and assume the photolysis degradation-elution of the DNA in BrdU-substituted areas. PMID- 1610117 TI - Heterosynapsis in two fertile but hypoprolific boars carriers of reciprocal translocations. AB - The authors report here two new cases of reciprocal translocations in two fertile and hypoprolific boars. Silver stained synaptonemal complexes in surface-spread pachytene nuclei from a boar heterozygous for a reciprocal translocation, and from another one carrying two different reciprocal translocations, were analyzed by electron microscopy. In such heterozygotes, cross-shaped quadrivalent configurations are expected to form in order to allow homologous pairing. In the same boar, the lengths of the fully synapsed arms of the quadrivalent varies from one quadrivalent to the other and heterosynapsis was obvious. Heterosynapsis was also observed with asymmetrical pairing of the non-homologous partners of the quadrivalent. This heterosynapsis is assumed to be a mechanism preventing spermatocyte loss, but inducing a secondary segregational type of impairment of fertility due to foetal wastage leading to reduced prolificacy. PMID- 1610118 TI - Different risks in two familial translocations t(9;12) with similar breakpoints. AB - The risk of offspring with unbalanced karyotypes born to carriers of reciprocal chromosomal translocation (RCT) is important to evaluate for further family planning and prenatal diagnosis. The authors describe two families with carriers of similar RCT concerning breakpoint positions and discuss the different individual risks for abnormal progeny. These translocations were studied by GTG, RBG and CBG banding. They have the same breakpoint on 9p, i.e. 9p22, and a different one on 12p, i.e. terminal (pter----p13) and intermediate (p11.2), respectively. The risk value of 27% for family 1 was obtained directly from the large enough pedigree (high risk) a risk value of about 5% was estimated for family 2, according to the guidelines of Stene and Stengel-Rutkowski (1988). The data show that similar translocations with only slight differences in the breakpoints position have different risks for unbalanced progeny. Results of these empiric findings may be used directly in genetic counselling of a family with RCT leading to a single imbalance of the same segment. PMID- 1610119 TI - Acrocallosal syndrome in a child with de novo inverted tandem duplication of 12p11.2-p13.3. AB - Report on the child of normal unrelated parents presenting the typical features of acrocallosal syndrome (craniofacial dysmorphy, mental deficiency, convulsive disorder, agenesis of corpus callosum, preaxial polydactyly "hallux duplex" of both feet, and in addition diabetes insipidus) in which a mirror duplication of nearly the entire short arm of chromosome 12 was discovered. Since the symptomatology of trisomy and tetrasomy 12p shows some overlap with acrocallosal syndrome a common origin of the monogenic disorder and the chromosomal phenotypes is discussed. PMID- 1610120 TI - A new case of monosomy for 17q25----qter due to a maternal translocation [t(3;17)(p12;q24)]. AB - An 18-month-old girl was found to have monosomy for 17q25----qter which resulted from an unequal crossing-over in the mother carrying an apparently balanced translocation 46, XX, t(3;17) (p12;q24). Clinical features of the proband included: cleft palate, micrognathia and glossoptosis. It seems to be the first reported case where a single band deletion in the long arm of chromosome 17 has ever been noted. PMID- 1610121 TI - Incontinentia pigmenti (type 1) and X;5 translocation. AB - The authors present a 5-year-old girl with total absence of speech, dysmorphic features, pigmented lesions on the legs, an abnormal EEG and otherwise normal intelligence representing a mild form of type 1 Incontinentia pigmenti associated with an (X;5) (p11.2;q35.2) apparently balanced translocation prenatally diagnosed. The seven previous translocation type 1 IP patients are reviewed and all have the same Xp11 breakpoint. Somatic cell hybrids have been made to further study this breakpoint and further define the putative type 1 IP gene. PMID- 1610122 TI - de novo inversion-duplication of 2q35-2qter without growth retardation. AB - A 7-year-old mentally retarded child was found to be the carrier of a de novo inversion-duplication of 2q35-2qter. His phenotype corresponded to that which is classically described in cases of partial trisomy of the long arm of chromosome 2; however, he did not show the growth retardation which usually characterizes this and other aneuploidy syndromes. PMID- 1610123 TI - Paracentric inversion of chromosome 14 plus rare 9p variant in a couple with habitual spontaneous abortion. AB - A couple presenting with habitual spontaneous abortion both showed a chromosome rearrangement. The male had an apparently balanced paracentric inversion of chromosome 14 - 46,XY,inv(14) (q11q32). The female had a karyotype with a rare large short arm variant of chromosome 9 - 46,XX,var(9) (p11p21). Testing of a living normal child showed that he had inherited both rearrangements. Family testing showed the chromosome 9 variant in three generations, with all carriers being of normal phenotype and intelligence. This study confirms that the presence of more than one chromosomal rearrangement can be compatible with normal development. This is useful for genetic counselling. Nevertheless when such cases arise, each must be individually assessed. PMID- 1610124 TI - A method for cytogenetic analysis of boar spermatozoa using hamster oocytes. AB - In this paper, the authors detail a method for displaying boar spermatozoa chromosomes using heterospecific zona-free hamster oocyte penetration technique. Semen samples from two Large-White boars having a normal spermogram were studied. The first one had a normal karyotype (38,XY), the second carried a reciprocal translocation rcp(3;7)(p1,3;q2,1). After in vitro fertilization by capacitated sperm, culture and cytogenetic analysis of hamster eggs we obtained metaphase spreads of spermatozoa chromosomes. The ratio of X- and Y-bearing spermatozoa was 49.2% and 50.8%, respectively. PMID- 1610125 TI - Bacterial meningitis. PMID- 1610126 TI - Cerebrospinal fluid penetration of antimicrobials. PMID- 1610127 TI - Duration of treatment of bacterial meningitis. PMID- 1610128 TI - Ceftriaxone and bacterial meningitis. A ten-year follow-up. PMID- 1610129 TI - Dexamethasone therapy of bacterial meningitis. PMID- 1610130 TI - Pathogenesis of central nervous system injury in bacterial meningitis. PMID- 1610131 TI - Etiology and management of neonatal bacterial meningitis. PMID- 1610132 TI - Prolonged and secondary fevers in childhood bacterial meningitis. PMID- 1610133 TI - Sequelae of acute bacterial meningitis in children. PMID- 1610134 TI - Hearing disorders in meningitis. PMID- 1610135 TI - Adverse outcome of bacterial meningitis due to delayed sterilization of cerebrospinal fluid. PMID- 1610136 TI - Seizures during bacterial meningitis. PMID- 1610137 TI - Recurrent bacterial meningitis. PMID- 1610138 TI - Bacterial meningitis in the immunocompromised host. PMID- 1610139 TI - Molecular mechanism of Haemophilus influenzae pathogenicity. PMID- 1610140 TI - The epidemiology of bacterial meningitis. PMID- 1610141 TI - Microbiology of bacterial meningitis pathogens. PMID- 1610142 TI - Role of immunological tests in diagnosis of bacterial meningitis. PMID- 1610143 TI - Bacterial meningitis: signs and symptoms. PMID- 1610145 TI - Patients satisfied with hip replacements. PMID- 1610146 TI - AORN revised statement on the patient and health care workers with human immunodeficiency virus (HIV) and other bloodborne diseases. PMID- 1610144 TI - Theoretical and practical considerations of antibiotic therapy for bacterial meningitis. PMID- 1610147 TI - Facial trauma. Management in the patient with multiple system injuries. PMID- 1610148 TI - Photodynamic therapy for bronchial and esophageal tumors. Perioperative implications. AB - Although still under investigation, clinical applications of PDT appear to have positive results. The success of PDT is being confirmed as investigative sites throughout the world are reporting remarkable results. Researchers hope that this will be one of the bright spots in the treatment of cancer. PMID- 1610149 TI - Surgical gloves. Measuring cost and barrier effectiveness. PMID- 1610150 TI - Barrier materials. Their influence on surgical wound infections. AB - Aseptic technique can best be described as an aggregation of reasonable practices performed in the surgical suite as part of the overall methodology in controlling or minimizing the possibility of infection. The key words in this definition are aggregation and reasonable. The real question is whether the surgical nursing community is prepared to reconsider and reassess the importance of a theoretical and reasonable, but not proven, practice that it has been advocating for almost two decades. From the evidence, it appears that a departure from the universal application of the barrier principle would not compromise the quality of care rendered to the surgical patient while at the same time prove to be economically and environmentally advantageous. PMID- 1610151 TI - Demystifying organ procurement. Initiating the protocols, understanding the sequence of events. PMID- 1610152 TI - Organ procurement in the operating room. Implications for perioperative nurses. PMID- 1610153 TI - Flash sterilization. Is it safe for routine use? PMID- 1610154 TI - Exploring the issues concerning augmentation mammoplasty. PMID- 1610155 TI - AORN testifies on priority issues; proposed bills address reimbursement, health care reform. PMID- 1610156 TI - A comparison of three anesthetic agents. PMID- 1610157 TI - A letter to Florence Nightingale. PMID- 1610158 TI - Using emergency blankets to keep ice frozen. PMID- 1610159 TI - Accuracy of estimates of forthcoming ingestion as a function of menu familiarity and dietary restraint. AB - Estimates of forthcoming intake were compared with amount eaten in women who were normal-weight restrained eaters, unrestrained eaters or overweight restrained eaters, for three four-course lunches of which the first consisted mainly of an Italian menu, the second and third mainly a Japanese menu. The differences between estimated and eaten amounts for the first and third lunch correlated negatively with degree of restraint. This indicates that those who score high on dietary restraint have learnt better ways of estimating their intake. No relation was found between the difference in estimated and eaten amount and degree of restraint during the second lunch. This indicates that the unfamiliarity of a meal makes it more difficult to predict how much of it would be satiating. PMID- 1610160 TI - Preferred salt levels and salt taste acuity in human subjects after ingestion of untasted salt. AB - We have examined whether salt loading alters the salt preference or salt taste acuity of nine human subjects on continuous low salt diet. Subjects were randomly assigned to either untasted salt tablets (120 mmol/day) or placebo over a 2-week period at the end of which salt preference and salt recognition thresholds were measured. Subjects then received the alternate substance for another 2 weeks and the measurements were repeated. While urinary Na+ and Cl- were significantly increased while on salt tablets, urinary volume, K+, urea and creatinine concentrations, blood pressure, body weight, salivary and plasma electrolyte concentrations were unchanged. Plasma renin and aldosterone levels were reduced while on salt tablets but not significantly. Salt tablets caused a significant increase in sodium recognition threshold but a significant decrease in salt addition to unsalted tomato juice and in ideal salt level assessed by presalted (150 mmol/l) tomato juice. Thus, an increase in untasted dietary salt may reduce salt preference in human subjects, a finding opposite to that with an increased, tasted salt intake over a similar period. PMID- 1610161 TI - Relationship of satiety to postprandial glycaemic, insulin and cholecystokinin responses. AB - The effect of plasma glucose on satiety and the capacity of carbohydrates to stimulate cholecystokinin (CCK) remain unclear. The aim of this study was to test the hypothesis that the magnitude of the postprandial plasma glucose and insulin response is inversely related to the CCK response and to subjective satiety. Seven healthy, male volunteers consumed equal carbohydrate portions (0.5 g/kg body weight) of six test meals (Rice Bubbles, Sustain, Vita-Brits, All-Bran, porridge and white bread) in random order after an overnight fast. An egg and bacon meal was consumed as a non-carbohydrate control providing 0.5 g protein/kg body weight. Serum CCK, plasma glucose and insulin and subjective satiety (measured by a rating scale) were assessed over 3 h and quantified using the glycaemic index (GI), insulin index (II), the peak satiety score and area under the incremental curve (AUC). The observed GIs (mean +/- SE) ranged from 42.5 +/- 2.6 for All-Bran to 116.2 +/- 11.4 for Rice Bubbles, using white bread as the reference food (GI = 100). Peak satiety scores varied eightfold from 0.21 +/- 0.4 for Sustain to 1.64 +/- 0.4 for All-Bran. Significant inverse relationships were observed between the peak satiety score and both the glycaemic and insulin index of the seven meals (r = -0.916, p less than 0.001 and r = -0.926, p less than 0.001). A direct relationship was observed between satiety (AUC) and the CCK response (AUC) (r = 0.73 p less than 0.01). The results suggest that glycaemic and insulin responses to carbohydrate foods are inversely proportional to the CCK response and satiety. PMID- 1610162 TI - Effects of intraruminal infusions of sodium salts on selection of hay and concentrate foods by sheep. AB - Infusion of salts of short-chain fatty acids into the rumen of sheep depresses food intake but the relative importance of the effect of the acids and of osmolality are not fully understood. Three experiments were carried out in which sodium acetate (NaAc) and sodium chloride (NaCl) were infused for 3 h at 4 mM/min and compared with water controls. The effects on the intakes of a concentrate food and hay were examined to study the effect of osmotic and acid manipulation of the rumen on dietary choice. In the first experiment the foods were continuously available while in the second and third the foods were given for 3 min at 1.5-h intervals. Salt infusions depressed concentrate intake without significant effect on the intake of hay. The effect of NaAc tended to be greater than that of NaCl and persisted after the end of infusion. The weight of concentrate eaten during the 3-min tests was significantly and negatively related to both acetate and sodium concentrations in rumen fluid. The weight of hay eaten was negatively related to concentrate intake. The results demonstrate that the treatments imposed had a differential effect on intake, only depressing that of the concentrate food. They also suggest that, as NaAc has a greater effect than NaCl, the influence on feeding is due both to the osmotic load and the acid effect. PMID- 1610163 TI - Variety seeking in the consumption of spread and cheese. AB - Consumers' (n = 807) desire for variety, as measured by the food-specific VARSEEK scale, was related to reported usage and purchase behavior for spread and cheese. Subjects' scoring high in variety seeking tendency showed more exploratory tendencies in purchase behavior, vicarious exploration and use innovativeness than did those scoring low on the scale. Variation reported in the use of cheese was related to variety seeking tendency more strongly than the variation in the use of spreads. The variation in cheese purchases was particularly high for well educated white collar workers between 31 and 50 years old and for female subjects living in urban areas of Finland. Some cross-product consistency in the variation in purchase behavior was found. The results suggest that certain product characteristics, such as sensory variation between alternatives, may determine whether the intrinsic desire for variety is expressed in product choice. PMID- 1610164 TI - In memoriam. Alan N. Epstein. PMID- 1610165 TI - Human intake and choice of foods at intervals after exercise. AB - Thirteen college-age men and women were submitted weekly to submaximal exercise for 2 h. After each exercise session, they were presented with the same meal composed of two high-protein, one high-lipid and two high-carbohydrate foods. The meal was offered at random 0, 30, 60, or 120 min after the 2-h exercise or 60 min after a session without exercise. As compared to a situation without exercise, both the pre-meal hunger rating and caloric intake were substantially increased 60 min after an exercise session. Also, after such exercise, hunger ratings increased with time and the later the meal, the larger was the amount consumed, both in total energy and as intake from carbohydrates but not lipids or proteins. PMID- 1610166 TI - Microbial reduction of manganese and iron: new approaches to carbon cycling. PMID- 1610167 TI - Cell surface redox potential as a mechanism of defense against photosensitizers in fungi. AB - The phytotoxin cercosporin, a singlet oxygen-generating photosensitizer, is toxic to plants, mice, and many fungi, yet the fungi that produce it, Cercospora spp., are resistant. We hypothesize that resistance to cercosporin may result from a reducing environment at the cell surface. Twenty tetrazolium dyes differing in redox potential were used as indicators of cell surface redox potential of seven fungal species differing in resistance to cercosporin. Resistant fungi were able to reduce significantly more dyes than were sensitive fungi. A correlation between dye reduction and cercosporin resistance was also observed when resistance levels of Cercospora species were manipulated by growth on different media. The addition of the reducing agents ascorbate, cysteine, and reduced glutathione (GSH) to growth media decreased cercosporin toxicity for sensitive fungi. None of these agents directly reduced cercosporin at the concentrations at which they protected fungi. Spectral and thin-layer chromatographic analyses of cercosporin solutions containing the different reducing agents indicated that GSH, but not cysteine or ascorbate, reacted with cercosporin. Resistant and sensitive fungi did not differ in endogenous levels of cysteine, GSH, or total thiols. On the basis of data from this and other studies, this report presents a model which proposes that cercosporin resistance results from the production of reducing power at the surfaces of resistant cells, leading to transient reduction and detoxification of the cercosporin molecule. PMID- 1610168 TI - Enzymatic iron oxidation by Leptothrix discophora: identification of an iron oxidizing protein. AB - An iron-oxidizing factor was identified in the spent culture medium of the iron- and manganese-oxidizing bacterial strain Leptothrix discophora SS-1. It appeared to be a protein, with an apparent molecular weight of approximately 150,000. Its activity could be demonstrated after fractionation of the spent medium by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A spontaneous mutant of L. discophora SS-1 was isolated which excreted neither manganese- nor iron-oxidizing activity, whereas excretion of other proteins seemed to be unaffected. Although the excretion of both metal-oxidizing factors was probably linked, the difference in other properties suggests that manganese and iron oxidation represent two different pathways. With a dot-blot assay, it was established that different bacterial species have different metal-oxidizing capacities. Whereas L. discophora oxidized both iron and manganese, Sphaerotilus natans oxidized only iron and two Pseudomonas spp. oxidized only manganese. PMID- 1610169 TI - Molecular cloning of genes related to aflatoxin biosynthesis by differential screening. AB - A differential hybridization strategy was used to clone genes associated with aflatoxin biosynthesis. A genomic library, formed between nuclear DNA and the pUC19 plasmid, was screened with three different cDNA probes by the colony hybridization procedure. Nineteen clones were selected; all were positively correlated with and presumably enriched with genes associated with aflatoxin production. Some of these clones were further characterized by using them as probes in Northern (RNA blot) hybridizations. Five clones hybridized strongly with some polyadenylated RNAs formed during the transition to or during idiophase when aflatoxin was produced. However, little or no corresponding hybridization occurred with polyadenylated RNAs formed in early and mid-log growth phase. Two of the clones were further used as probes to hybridize with polyadenylated RNAs formed under aflatoxin-permissive and nonpermissive temperatures. Hybridization occurred with RNA species formed under the permissive temperature only. PMID- 1610170 TI - Effect of different holding regimens on the intestinal microflora of herring (Clupea harengus) larvae. AB - The aerobic intestinal microflora of 2-week-old herring (Clupea harengus) larvae was characterized by using conventional microbiological methods and electron microscopy. Larvae were hatched and kept in filtered seawater or in seawater with penicillin and streptomycin. The gastrointestinal tract of herring larvae is essentially a straight tube divided into two compartments. Light microscopy revealed bacteria present in a progressively increasing amount throughout the length of the gastrointestinal tract from esophagus to anus. The posterior region of the intestinal lumen appeared completely occluded with bacteria. The intestinal microflora consisted mainly of members of the genera Pseudomonas and Alteromonas in the larvae incubated in filtered seawater, whereas Flavobacterium spp. dominated in larvae exposed to antibiotics. The intestinal microflora of untreated fish larvae was sensitive to all tested antibiotics, whereas multiple resistance was found in the intestinal microflora of the group given antibiotics. Thus, a dramatic change in the microflora resulted from incubation with antibiotics. Nonpigmented yeasts were detected in both larval groups. Ciliated epithelial cells were observed in the midgut, probably propeling bacteria towards the hindgut, where endocytosis of bacteria has been demonstrated. These findings suggest that transport and sequestering mechanisms resembling those of invertebrates may be found in the gut of fish larvae. The possible significance for larval health and nutrition is discussed. PMID- 1610171 TI - Identification of two proline transport systems in Staphylococcus aureus and their possible roles in osmoregulation. AB - The food-borne pathogen Staphylococcus aureus is distinguished from other food borne pathogens by its ability to grow at water activity values below 0.90. Previous studies have indicated that proline accumulation mediated by transport represents a primary osmoregulatory strategy utilized by this bacterium (C. B. Anderson and L. D. Witter, Appl. Environ, Microbiol. 43:1501-1503, 1982; I. Koujima, H. Hayashi, K. Tomochika, A. Okabe, and Y. Kanemasa, Appl. Environ. Microbiol. 35:467-470, 1978; K. J. Miller, S. C. Zelt, and J.-H. Bae, Curr. Microbiol. 23:131-137, 1991). In this study, we demonstrate the presence of two proline transport systems within whole cells of S. aureus, a high-affinity transport system (Km, 7 microM) and a low-affinity transport system (Km, 420 microM). Our results indicate that the low-affinity proline transport system is osmotically activated and is the primary system responsible for the accumulation of proline by this pathogen during growth at low water activity. PMID- 1610172 TI - Effects of chlorobenzoate transformation on the Pseudomonas testosteroni biphenyl and chlorobiphenyl degradation pathway. AB - Bacterial conversion of biphenyl (BP) and chlorobiphenyls (CBPs) to benzoates and chlorobenzoates (CBAs) proceeds by introduction of molecular oxygen at the 2,3 position, followed by a 1,2-meta cleavage of the molecule. Complete mineralization of CBPs requires the presence of two sets of genes, one for the transformation fo CBPs into CBAs and a second for the degradation of CBAs. It has been shown previously that removal of the CBAs produced from the degradation of CBPs is essential for efficient degradation of CBPs. In this study we confirmed that CBAs inhibit BP and CBP transformation in Pseudomonas testosteroni B-356. Among the three monochlorobenzoates tested, 3-chlorobenzoate was the most effective inhibitor. Furthermore, we found that in strain B-356, CBA transformation is controlled by BP-induced oxygenases that are not present in benzoate-grown cells. We found that this BP-linked CBA transformation pathway transformed CBAs produced from CBPs into several metabolites, including chlorocatechols and corresponding muconic semialdehydes. These metabolites inhibited the 2,3-dihydroxybiphenyl 1,2-dioxygenase, while CBAs by themselves had no effect on this enzyme. Therefore, on the basis of this and other observations, it appears that when CBAs produced from CBPs accumulate in the growth medium, they are converted into unproductive metabolites that reduce the flux of the BP and CBP degradation pathway. The practical implications of these interactions on the microbial degradation of polychlorinated BPs are also discussed. PMID- 1610173 TI - Metabolites formed during anaerobic transformation of toluene and o-xylene and their proposed relationship to the initial steps of toluene mineralization. AB - Strain T1 is a facultative bacterium that is capable of anaerobic toluene degradation under denitrifying conditions. While 80% of the carbon from toluene is either oxidized to carbon dioxide or assimilated into cellular carbon, a significant portion of the remainder is transformed into two dead-end metabolites. These metabolites were produced simultaneous to the mineralization of toluene and were identified as benzylsuccinic acid and benzylfumaric acid. Identification was based on comparison of mass spectra of the methyl esters of the metabolites and authentic compounds that were chemically synthesized. Strain T1 is also capable of o-xylene transformation during growth on toluene. o-Xylene does not serve as a source of carbon and is not mineralized. Rather, it is transformed to analogous dead-end metabolites, (2-methylbenzyl)-succinic acid and (2-methylbenzyl)-fumaric acid. o-Xylene transformation also occurred during growth on succinic acid, which suggests that attack of the methyl group by succinyl-coenzyme A is a key reaction in this transformation. We reason that the main pathway for toluene oxidation to carbon dioxide involves a mechanism similar to that for the formation of the metabolites and involves an attack of the methyl group of toluene by acetyl-coenzyme A. PMID- 1610174 TI - Biodegradation of the herbicide bromoxynil (3,5-dibromo-4-hydroxybenzonitrile) by purified pentachlorophenol hydroxylase and whole cells of Flavobacterium sp. strain ATCC 39723 is accompanied by cyanogenesis. AB - A pentachlorophenol (PCP)-degrading Flavobacterium sp. (strain ATCC 39723) degraded bromoxynil with the production of bromide and cyanide. No aromatic intermediates were detected in the spent culture fluid. The cyanide produced upon bromoxynil metabolism was inhibitory to the Flavobacterium sp. Whole cells degraded PCP more rapidly than they did bromoxynil. Bromoxynil metabolism and PCP metabolism were coinduced, either substrate serving as the inducer. Purified PCP hydroxylase degraded bromoxynil with stoichiometric accumulation of cyanide and without bromide production. A product accumulated which was more hydrophilic than bromoxynil upon high-pressure liquid chromatographic analysis and which, when analyzed by gas chromatography-mass spectrometry, had a mass spectrum consistent with that expected for dibromohydroquinone. PCP hydroxylase consumed NADPH, oxygen, and bromoxynil in a 2:1:1 molar ratio, producing 1 mol of cyanide per mol of bromoxynil degraded. We propose a pathway by which bromoxynil is metabolized by the same enzymes which degrade PCP. The initial step in the pathway is the conversion of bromoxynil to 2,6-dibromohydroquinone by PCP hydroxylase. In addition to its utility for decontaminating PCP-polluted sites, the Flavobacterium sp. may be useful for decontaminating bromoxynil spills. This is the first report of cyanide production accompanying the metabolism of a benzonitrile derivative. PMID- 1610175 TI - Properties of a 72-kilodalton mosquitocidal protein from Bacillus thuringiensis subsp. morrisoni PG-14 expressed in B. thuringiensis subsp. kurstaki by using the shuttle vector pHT3101. AB - The mosquitocidal properties of Bacillus thuringiensis subsp. israelensis and B. thuringiensis subsp. morrisoni PG-14 are attributable to protein inclusions grouped together within a parasporal body. In both of these strains, the mosquitocidal activity resides in proteins with molecular masses of 27, 72, 128, and 135 kDa. In an attempt to determine the toxicity of each protein, the shuttle vector pHT3101 was used to express the cryIVD gene (encoding the 72-kDa CryIVD protein) from B. thuringiensis subsp. morrisoni in an acrystalliferous mutant of B. thuringiensis subsp. kurstaki. With this system, parasporal inclusions of the 72-kDa protein were obtained that were comparable in size, shape, and toxicity to those produced by parental B. thuringiensis subsp. morrisoni. The inclusions were bar shaped, measured 500 by 300 by 150 nm, and were easily visible with phase contrast microscopy by 16 h of cell growth. A 50% lethal concentration of 64 ng/ml for these inclusions was determined in bioassays against fourth instars of Culex quinquefasciatus, which was similar to the 50% lethal concentration of 55 ng/ml obtained for the 72-kDa inclusion from B. thuringiensis subsp. israelensis. In contrast, expression of the cryIVD gene in Escherichia coli was very low and only detectable by immunoblot analysis. These results demonstrate that the pHT3101-B. thuringiensis expression system can be used to express the CryIVD protein in quantities and with properties comparable to that obtained with the natural host. This system may prove useful for the expression of other B. thuringiensis proteins and, in particular, for reconstitution experiments with inclusions produced by the mosquitocidal subspecies of B. thuringiensis. PMID- 1610176 TI - Isolation and partial characterization of an 87-kilodalton beta-1,3-glucanase from Bacillus circulans IAM1165. AB - Bacillus circulans IAM1165 produces at least two extracellular beta-1,3 glucanases that lyse fungal cell walls. One of these extracellular enzymes was purified to homogeneity. The molecular mass was 87 kDa, and the pI was 4.3. The optimum temperature of the enzyme reaction was 70 degrees C when laminarin (a soluble beta-1,3-glucan) was used as the substrate. The pH range of the enzyme was broad (pH 4.5 to 9.0), and the optimum pH was 6.5. The enzyme is an endo beta 1,3-glucanase and has a random cleavage pattern. PMID- 1610177 TI - Characterization of an extracellular protease inhibitor of Bacillus brevis HPD31 and nucleotide sequence of the corresponding gene. AB - A novel proteinaceous protease inhibitor was isolated from the culture supernatant of Bacillus brevis HPD31. The protease inhibitor of B. brevis (designated BbrPI) was produced extracellularly in multiple forms having at least three different molecular weights. One of them, BbrPI-a, was purified to near homogeneity and only showed inhibitory activity toward serine proteases, such as trypsin, chymotrypsin, and subtilisin. BbrPI was presumed to form a trypsin inhibitor complex in a molar ratio of 1:1. The inhibitor was found to be heat resistant at neutral and acidic pHs. The gene coding for BbrPI was cloned into Escherichia coli, and its nucleotide sequence was determined. The sequence suggested that BbrPI is produced with a signal peptide of 24 amino acid residues. The amino acid sequence of the protein deduced from the DNA sequence contained the amino acid sequences of amino termini of the inhibitors, a, b, and c, and their putative precursor determined chemically. The molecular weight of the precursor was about 33,000, and the molecular weights of inhibitors a, b, and c were about 22,000, 23,500, and 24,000, respectively. It is presumed that the secreted precursor protein, which is probably inactive, is cleaved by protease into several active protease inhibitor molecules. BbrPI shows no significant homology to the protease inhibitors described previously and is unique in not having any cysteine residues in its molecule. PMID- 1610178 TI - DNA relatedness among strains of the sweet potato pathogen Streptomyces ipomoea (Person and Martin 1940) Waksman and Henrici 1948. AB - DNA relatedness among 28 putative strains of Streptomyces ipomoea from geographically diverse locations and the type strain, NRRL B-12321, was determined spectrophotometrically. The data confirm that these 28 strains are not closely related genetically to the plant-pathogenic species Streptomyces scabies (39% DNA relatedness) or Streptomyces acidiscabies (17% DNA relatedness) or any other major blue-spored Streptomyces species (less than 30% DNA relatedness). Of the 29 strains examined, 4 could be clearly distinguished from S. ipomoea on the basis of morphological criteria, i.e., they had gray rather than blue spores and produced melanin pigment, and their low DNA relatedness to authentic S. ipomoea strains confirmed their original misidentification. The remaining 25 S. ipomoea strains exhibited high DNA relatedness among themselves (76 to 100% homology), even though they had been isolated in different locations throughout the United States and Japan. The avirulent type strain, NRRL B-12321, exhibited slightly lower DNA relatedness with the virulent strains of S. ipomoea (85% average DNA relatedness) than was observed among the virulent strains (average of 96% DNA relatedness). PMID- 1610180 TI - Intestinal colonization potential of turbot (Scophthalmus maximus)- and dab (Limanda limanda)-associated bacteria with inhibitory effects against Vibrio anguillarum. AB - Of more than 400 bacteria isolated from turbot (Scophthalmus maximus), 89 have previously been shown to inhibit the in vitro growth of the fish pathogen Vibrio anguillarum. The aim of the present study was to investigate the potential of seven of these strains, as well as of intestinal isolates (four strains) from a closely related fish, dab (Limanda limanda), for colonizing farmed turbot as a means of protecting the host from infection by V. anguillarum. In addition, the inhibitory effect of these strains on the pathogen was further studied. Colonization potential was measured by the capacity of the strains to adhere to and grow in turbot intestinal mucus. These parameters were also used to investigate the potential of V. anguillarum to amplify in the turbot intestinal tract. Because of the observed rapid growth of V. anguillarum in intestinal mucus, it can be proposed that the intestinal tract is a site for V. anguillarum multiplication. Strains isolated from the intestine showed greater capacity for adhesion to and growth in fish intestinal mucus than did the pathogen and the skin mucus isolates. All of the isolates released metabolites into the culture medium that had inhibitory effects against V. anguillarum. The results are discussed with emphasis on administering bacteria of host origin to farmed turbot in order to control V. anguillarum-induced disease. PMID- 1610179 TI - Pseudomonas putida KT2442 cultivated on glucose accumulates poly(3 hydroxyalkanoates) consisting of saturated and unsaturated monomers. AB - The biosynthesis of poly(3-hydroxyalkanoates) (PHAs) by Pseudomonas putida KT2442 during growth on carbohydrates was studied. PHAs isolated from P. putida cultivated on glucose, fructose, and glycerol were found to have a very similar monomer composition. In addition to the major constituent 3-hydroxydecanoate, six other monomers were found to be present: 3-hydroxyhexanoate, 3-hydroxyoctanoate, 3-hydroxydodecanoate, 3-hydroxydodecenoate, 3-hydroxytetradecanoate, and 3 hydroxytetradecenoate. The identity of all seven 3-hydroxy fatty acids was established by gas chromatography-mass spectrometry, one-dimensional 1H-nuclear magnetic resonance, and two-dimensional double-quantum filtered correlation spectroscopy 1H-nuclear magnetic resonance. The chemical structures of the monomer units are identical to the structure of the acyl moiety of the 3 hydroxyacyl-acyl carrier protein intermediates of de novo fatty acid biosynthesis. Furthermore, the degree of unsaturation of PHA and membrane lipids is similarly influenced by shifts in the cultivation temperature. These results strongly indicate that, during growth on nonrelated substrates, PHA monomers are derived from intermediates of de novo fatty acid biosynthesis. Analysis of a P. putida pha mutant and complementation of this mutant with the cloned pha locus revealed that the PHA polymerase genes necessary for PHA synthesis from octanoate are also responsible for PHA formation from glucose. PMID- 1610181 TI - Anaerobic transformation and toxicity of trichlorophenols in a stable enrichment culture. AB - The transformation and toxicity of trichlorophenols (TCPs) were studied with a methanogenic enrichment culture derived from sewage sludge. Transformation of TCPs rapidly resumed after heating of the culture at *) degrees C for 1 h, suggesting that the dechlorinating bacteria are spore-forming anaerobes. 2,4,6 TCP was rapidly dechlorinated via 2,4-dichlorophenol to 4-chlorophenol. During the transformation of 2,4,6-TCP, the most probable number of dechlorinating bacteria increased by 4 orders of magnitude. The most extensive dechlorination was observed in media with complex carbon sources such as yeast extract, peptone, and Casamino Acids, but glucose, galactose, and lactose were also used by the consortium. Experiments using chloramphenicol indicated that the reductive dechlorination of 2,4,6-TCP was regulated by an inducible enzyme system. The highest initial concentration at which dechlorination of 2,4,6-TCP was observed was 400 microM. 2,4,5-TCP and 3,4,5-TCP were dechlorinated to, respectively, 3,4 dichlorophenol and 3-chlorophenol at initial concentrations of less than or equal to 40 microM. Toxicity for the acid-producing and methanogenic bacteria in the consortium was a function of chemical structure, as the inhibition of these activities increased from 2,4,6-TCP, via 2,4,5-TCP, to 3,4,5,-TCP. PMID- 1610182 TI - Cloning, sequencing, and expression in Escherichia coli of lcnB, a third bacteriocin determinant from the lactococcal bacteriocin plasmid p9B4-6. AB - On the bacteriocin plasmid p9B4-6 of Lactococcus lactis subsp. cremoris 9B4, a third bacteriocin determinant was identified. The genes encoding bacteriocin production and immunity resided on a 1.2-kb CelII-ScaI fragment and were located adjacent to one of two previously identified bacteriocin operons (M. J. van Belkum, B. J. Hayema, R. E. Jeeninga, J. Kok, and G. Venema, Appl. Environ. Microbiol. 57:492-498, 1991). The fragment was sequenced and analyzed by deletion and mutation analyses. The bacteriocin determinant consisted of two genes which were transcribed as an operon. The first gene (lcnB), containing 68 codons, was involved in bacteriocin activity. The second gene (lciB) contained 91 codons and was responsible for immunity. The specificity of this novel bacteriocin, designated lactococcin B, was different from that of the other two bacteriocins specified by p9B4-6. Part of the nucleotide sequence of the lactococcin B operon was similar to a nucleotide sequence also found in the two other bacteriocin operons of p9B4-6. This conserved region encompassed a nucleotide sequence upstream of the bacteriocin gene and the 5' part of the gene. When the lactococcin B operon was expressed in Escherichia coli by using a T7 RNA polymerase-specific promoter, antagonistic activity could be detected. PMID- 1610183 TI - Measurement of marine picoplankton cell size by using a cooled, charge-coupled device camera with image-analyzed fluorescence microscopy. AB - Accurate measurement of the biomass and size distribution of picoplankton cells (0.2 to 2.0 microns) is paramount in characterizing their contribution to the oceanic food web and global biogeochemical cycling. Image-analyzed fluorescence microscopy, usually based on video camera technology, allows detailed measurements of individual cells to be taken. The application of an imaging system employing a cooled, slow-scan charge-coupled device (CCD) camera to automated counting and sizing of individual picoplankton cells from natural marine samples is described. A slow-scan CCD-based camera was compared to a video camera and was superior for detecting and sizing very small, dim particles such as fluorochrome-stained bacteria. Several edge detection methods for accurately measuring picoplankton cells were evaluated. Standard fluorescent microspheres and a Sargasso Sea surface water picoplankton population were used in the evaluation. Global thresholding was inappropriate for these samples. Methods used previously in image analysis of nanoplankton cells (2 to 20 microns) also did not work well with the smaller picoplankton cells. A method combining an edge detector and an adaptive edge strength operator worked best for rapidly generating accurate cell sizes. A complete sample analysis of more than 1,000 cells averages about 50 min and yields size, shape, and fluorescence data for each cell. With this system, the entire size range of picoplankton can be counted and measured. PMID- 1610184 TI - Inhibition of Listeria monocytogenes by fatty acids and monoglycerides. AB - Fatty acids and monoglycerides were evaluated in brain heart infusion broth and in milk for antimicrobial activity against the Scott A strain of Listeria monocytogenes. C12:0, C18:3, and glyceryl monolaurate (monolaurin) had the strongest activity in brain heart infusion broth and were bactericidal at 10 to 20 micrograms/ml, whereas potassium (K)-conjugated linoleic acids and C18:2 were bactericidal at 50 to 200 micrograms/ml. C14:0, C16:0, C18:0, C18:1, glyceryl monomyristate, and glyceryl monopalmitate were not inhibitory at 200 micrograms/ml. The bactericidal activity in brain heart infusion broth was higher at pH 5 than at pH 6. In whole milk and skim milk, K-conjugated linoleic acid was bacteriostatic and prolonged the lag phase especially at 4 degrees C. Monolaurin inactivated L. monocytogenes in skim milk at 4 degrees C, but was less inhibitory at 23 degrees C. Monolaurin did not inhibit L. monocytogenes in whole milk because of the higher fat content. Other fatty acids tested were not effective in whole or skim milk. Our results suggest that K-conjugated linoleic acids or monolaurin could be used as an inhibitory agent against L. monocytogenes in dairy foods. PMID- 1610185 TI - Insecticidal properties of a crystal protein gene product isolated from Bacillus thuringiensis subsp. kenyae. AB - A protoxin gene, localized to a high-molecular-weight plasmid from Bacillus thuringiensis subsp. kenyae, was cloned on a 19-kb BamHI DNA fragment into Escherichia coli. Characterization of the gene revealed it to be a member of the CryIE toxin subclass which has been reported to be as toxic as the CryIC subclass to larvae from Spodoptera exigua in assays with crude E. coli extracts. To directly test the purified recombinant gene product, the gene was subcloned as a 4.8-kb fragment into an expression vector resulting in the overexpression of a 134-kDa protein in the form of phase-bright inclusions in E. coli. Treatment of solubilized inclusion bodies with either trypsin or gut juice from the silkworm Bombyx mori resulted in the appearance of a protease-resistant 65-kDa protein. In force-feeding bioassays, the purified activated protein was highly toxic to larvae of B. mori but not to larvae of Choristoneura fumiferana. In diet bioassays with larvae from S. exigua, the purified protoxin was nontoxic. However, prior activation of the protoxin by tryptic digestion resulted in the appearance of some toxic activity. These results demonstrate that this new subclass of protein toxin may not be useful for the control of Spodoptera species as previously reported. Hierarchical clustering of the nine known lepidopteran specific CryI toxin subclasses through multiple sequence alignment suggests that the toxins fall into four possible subgroups or clusters. PMID- 1610186 TI - Construction of a 3-chlorobiphenyl-utilizing recombinant from an intergeneric mating. AB - Recombinant Pseudomonas sp. strain CB15, which grows on 3-chlorobiphenyl (3CB), was constructed from Pseudomonas sp. strain HF1, which grows on 3-chlorobenzoate, and from Acinetobacter sp. strain P6, which grows on biphenyl, by using a continuous amalgamated culture apparatus. DNA from strains CB15 and HF1 hybridized very strongly to each other, while hybridization between both parental strains, HF1 and P6, was negligible. However, DNA from the recombinant CB15 hybridized moderately to strongly with three specific fragments of parental strain P6. Strains HF1 and P6 did not grow on 3CB, but recombinant strain CB15 mineralized this compound and released inorganic chloride. When growing on 3CB, strain CB15 accumulated brown products, one of which was identified as 3-chloro-5 (2'-hydroxy-3'-chlorophenyl)-1,2-benzoquinone by mass spectrometry. Emulsification and mechanical fragmentation greatly increased the rate of 3CB mineralization by strain CB15. At least three methods of inhibition from catecholic intermediates may account for slow growth on 3CB. The meta fission of 2,3-dihydroxybiphenyl (the nonchlorinated analog of the metabolic intermediate 3 chloro-2',3'-dihydroxybiphenyl) was affected by substrate inhibition (Vmax = 359 nmol.min-1.mg-1, Km = 114 microM, Kss [the inhibition constant] = 951 microM) and was also inhibited by 3-chlorocatechol. The ortho fission of 3-chlorocatechol, a degradation product, followed Michaelis-Menten kinetics (Vmax = 365 nmol.min-1.mg 1, Km = 1 microM), but the addition of 2,3-dihydroxybiphenyl inhibited the reaction (Ki = 0.87 microM).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610187 TI - Reduction of Campylobacter jejuni colonization of chicks by cecum-colonizing bacteria producing anti-C. jejuni metabolites. AB - Cecum-colonizing bacteria were isolated from Campylobacter jejuni-free White Leghorn (Gallus domesticus) laying hens and screened for the ability to produce anti-C. jejuni metabolites. Nine isolates were obtained that possessed this characteristic. The peroral administration of the nine isolates as a mixture (ca. 10(9) per chick) to 1-day-old chicks was followed 1 week later by peroral inoculation of Campylobacter jejuni (ca. 10(9) per chick) to determine if the cecal isolates could protect chicks from colonization by campylobacters. The nine strain mixture of cecal bacteria provided from 41 to 85% protection from C. jejuni colonization. The protective bacteria were reduced to a mixture of three strains on the basis of their ability to utilize mucin as a sole substrate for growth. These strains included Klebsiella pneumoniae 23, Citrobacter diversus 22, and Escherichia coli (O13:H-) 25. Four feeding trials with this three-strain mixture provided from 43 to 100% (average, 78%) protection from C. jejuni colonization. The dominant cecal bacterium of chicks treated with the three strain mixture was consistently E. coli O13:H-. Similarly, three trials with only E. coli 25 used as the protective bacterium resulted in 49 to 72% (average, 59%) protection from C. jejuni colonization, with E. coli O13:H- being the dominant cecal bacterium in all cases. Although not completely effective, E. coli 25 substantially reduced the incidence of C. jejuni colonization of chicks. For all trials, fewer C. jejuni were present in the ceca of colonized chicks receiving the protective bacteria before exposure to C. jejuni than in chicks receiving only C. jejuni.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610188 TI - Use of monoclonal antibodies to demonstrate different sites with different functional characteristics in a bacterial lipase from Pseudomonas aeruginosa YS 7. AB - Structural and functional features of the extracellular lipase from the low-water tolerant bacterium Pseudomonas aeruginosa YS-7 were studied immunochemically with the aid of monoclonal antibodies (MAbs) raised against the enzyme. Fourteen different MAbs were obtained, verified as immunoglobulin G types, and characterized by their interaction with the enzyme in relation to (i) inhibition of activity of free enzyme, (ii) inhibition of activity of adsorbed enzyme, (iii) interaction with the cell-bound enzyme, and (iv) inhibition of adherence to hexadecane droplets. Four of the MAbs exhibiting the highest binding constants (Kapp greater than 10(8) M-1) were selected for further study of the lipase. Their binding to the enzyme was assayed by means of adapted enzyme-linked immunosorbent assay techniques. Use of these MAbs in single or dual binding procedures made it possible to reveal several distinct sites on the lipase macromolecule. Two of these are functional sites, one for hydrophobic adhesion (binds MAb 5) and the other (binds MAb 1) for implementation of its hydrolytic activity. A third binding site (binds MAb 8) does not participate directly in either of the above functions. A fourth binding site (binds MAb 10) appears to be involved in the active expression of the enzyme. The cell-associated form of the lipase seems to be located on the external surface of the cells with its active site exposed. It appears to be anchored to the outer membrane of the cells by means of its hydrophobic region in a way that resembles its adherence to hydrophobic surfaces such as hexadecane droplets. PMID- 1610189 TI - Disinfection of drinking water by using a novel electrochemical reactor employing carbon-cloth electrodes. AB - A novel electrochemical reactor employing carbon-cloth electrodes was constructed for disinfection of drinking water. Escherichia coli K-12 (10(2) cells per cm3) was sterilized when a cell suspension was passed through the reactor at a dilution rate of 6.0 h-1, and a potential of 0.7 V versus a saturated calomel electrode was applied to an electrode. The survival ratio increased with increasing dilution rate but was less than 0.1% at dilution rates of less than 6.0 h-1. Although the survival ratio increased with increasing cell concentration above 10(3) cells per cm3, the disinfection rate also increased. The disinfection rate was 6.0 x 10(2) cells per cm3 per h at a cell concentration of 10(2) cells per cm3. Continuous sterilization of E. coli cells was carried out for 24 h. Sterilization is based on an electrochemical reaction between the electrode and the cell which is mediated by intracellular coenzyme A. Sterilization of drinking water by using this reactor was successfully performed, demonstrating the potential of such a reactor for clean and efficient water purification. PMID- 1610190 TI - Light-dependent degradation of nitrophenols by the phototrophic bacterium Rhodobacter capsulatus E1F1. AB - Rhodobacter capsulatus E1F1, a phototrophic purple nonsulfur bacterium capable of photoassimilating nitrate or nitrite, grew phototrophically in the presence of mono- and dinitrophenols with acetate as a carbon source, the highest growth levels being obtained under microaerobic conditions. Utilization of 2,4 dinitrophenol was strictly light dependent, was inhibited by O2 and by ammonium, and took place with the simultaneous and stoichiometric production of 2-amino-4 nitrophenol, which accumulated in the medium and was poorly used for further growth in anaerobiosis. Metabolism of mononitrophenols was also light dependent but was activated by O2 and by ammonium. Metabolism of nitrophenols seemed to depend on inducible systems which were repressed in nitrogen-starved cells. Induction of the in vivo 2,4-dinitrophenol reducing system was strongly inhibited by chloramphenicol. PMID- 1610191 TI - Potential early intermediates in anaerobic benzoate degradation by Rhodopseudomonas palustris. AB - Alkali-treated extracts of Rhodopseudomonas palustris growing photosynthetically on benzoate were examined by gas chromatography/mass spectrometry for partially reduced benzoate derivatives. Two cyclic dienes, cyclohexa-2,5-diene-1 carboxylate and cyclohexa-1,4-diene-1-carboxylate, were detected. Either compound supported cell growth as effectively as benzoate. These results suggest that these cyclohexadienecarboxylates, probably as their coenzyme A esters, are the initial reduction products formed during anaerobic benzoate metabolism by R. palustris. PMID- 1610192 TI - Comparison of acetate utilization among strains of an aceticlastic methanogen, Methanothrix soehngenii. AB - The kinetics of acetate utilization by concentrated suspensions of cells was examined in five strains of Methanothrix soehngenii. The rate of acetate utilization by all strains was dependent on the initial acetate concentration and followed simple Michaelis-Menten kinetics. The ability to utilize acetate differed among the various strains of M. soehngenii and was highest in the strain designated MTAS. PMID- 1610193 TI - Differentiation of Listeria monocytogenes, Listeria innocua, Listeria ivanovii, and Listeria seeligeri by pulsed-field gel electrophoresis. AB - Clamped homogeneous electric field analysis of Listeria DNA with ApaI, AscI, SmaI, or NotI revealed species- and serotype-specific differences in genomic fingerprints. Clamped homogeneous electric field analysis may prove useful, therefore, in epidemiologic studies. Also, the summation of individually sized AscI fragments of genomic DNA from L. monocytogenes serotype 4b 101M and Scott A indicated genome lengths of 2,925 and 3,046 kb, respectively. PMID- 1610194 TI - Detection of Pediococcus spp. in brewing yeast by a rapid immunoassay. AB - A membrane immunofluorescent-antibody test was developed to detect diacetyl producing Pediococcus contaminants in brewery pitching yeast (yeast [Saccharomyces cerevisiae] slurry collected for reinoculation). Centrifugations at 11 and 5,100 x g separate yeast cells from bacteria and concentrate the bacteria, respectively. Pelleted bacteria resuspended and trapped on a black membrane filter are reacted with monoclonal antibodies specific for cell surface antigens and then with fluorescein-conjugated indicator antibodies. Whether pitching yeast is contaminated with pediococci at 0.001% is determined in less than 4 h. The sensitivity of the assay is 2 orders of magnitude below the Pediococcus detection limit of direct microscopy. PMID- 1610195 TI - Comparison of assimilable organic carbon and UV-oxidizable carbon for evaluation of ultrapure-water systems. AB - Bacterial growth potential was measured in an ultrapure-water pilot plant by modified assimilable organic carbon (AOC) and UV-oxidizable carbon tests. An ion exchange unit increased UV-oxidizable carbon, yet did not significantly (P greater than or equal to 0.05) alter AOC values. UV radiation decreased UV oxidizable carbon and increased AOC. PMID- 1610196 TI - Production of an extracellular polyethylene-degrading enzyme(s) by Streptomyces species. AB - Extracellular culture concentrates were prepared from Streptomyces viridosporus T7A, Streptomyces badius 252, and Streptomyces setonii 75Vi2 shake flask cultures. Ten-day-heat-treated (70 degrees C) starch-polyethylene degradable plastic films were incubated with shaking with active or inactive enzyme for 3 weeks (37 degrees C). Active enzyme illustrated changes in the films' Fourier transform infrared spectra, mechanical properties, and polyethylene molecular weight distributions. PMID- 1610197 TI - Use of colistin-polymyxin B-cellobiose agar for isolation of Vibrio vulnificus from the environment. AB - Colistin-polymyxin B-cellobiose agar was employed for the isolation of Vibrio vulnificus from shellfish. Isolates were examined phenotypically and with a gene probe and monoclonal antibody specific for V. vulnificus. Results indicated that colistin-polymyxin B-cellobiose agar is superior to both sodium dodecyl sulfate polymyxin B-sucrose agar and thiosulfate-citrate-bile salts-sucrose agar in its ability to select and differentiate this species from background vibrios. PMID- 1610198 TI - Effect of nitrogen limitation on long-side-chain poly-beta-hydroxyalkanoate synthesis by Pseudomonas resinovorans. AB - Pseudomonas resinovorans produced poly-beta-hydroxyalkanoates (PHAs) when grown on hydrocarbons but not on glucose. In a chemostat culture, the PHA composition was beta-hydroxybutyrate (C4)-beta-hydroxyhexanoate (C6)-beta-hydroxyoctanoate (C8)-beta-hydroxydecanoate (C10) (1:15:75:9) on octanoate and C4-C6-C8-C10 (8:62:23:7) on hexanoic acid. Contrary to the reported behavior of Pseudomonas oleovorans, the PHA accumulation rate increased under ammonium limitation on octanoate. PMID- 1610199 TI - Filtration sizes of human immunodeficiency virus type 1 and surrogate viruses used to test barrier materials. AB - Filters with well-defined holes were used to determine the effective diameters in buffer of human immunodeficiency virus type 1, herpes simplex virus type 1, and four bacteriophages (phi X174, T7, PRD1, and phi 6), which may serve as surrogate viruses for testing barrier materials. Bacteriophages phi 6 and PRD1 most closely model human immunodeficiency virus type 1 in filtration size. PMID- 1610200 TI - The plasmid-encoded lactococcal envelope-associated proteinase is encoded by a chromosomal gene in Lactococcus lactis subsp. cremoris BC101. AB - The plasmid-free strain Lactococcus lactis subsp. cremoris BC101 produced an extracellular proteinase physicochemically similar to the proteinase encoded by the plasmid-linked prtP gene of other lactococcal strains. The absence of detectable plasmids in strain BC101 indicated that the prtP proteinase gene may be chromosomally located. The chromosomal linkage of the prtP proteinase gene in BC101 was confirmed by pulsed-field electrophoresis of chromosomal DNA and hybridization, using as a probe the plasmid-linked prtP gene from L. lactis subsp. cremoris Wg2. The prtM gene necessary for the maturation of the proteinase was also chromosomally located adjacent to prtP in BC101. By using as a hybridization probe the ISS1-like element ISS1W, which is found adjacent to the proteinase genes in both pWV05 and pSK111, specific homology to the chromosomal fragment containing the proteinase gene was found. DNA sequencing of a polymerase chain reaction product of chromosomal DNA upstream from prtM revealed a 123 nucleotide sequence which was 100% identical to the equivalent sequence in the ISS1W-containing plasmid. The terminal inverted repeat (18 nucleotides) of the ISS1W element was found in this sequenced DNA. These findings suggest that the chromosomal proteinase gene is organized in a fashion similar to that of the plasmid-linked proteinase gene. PMID- 1610201 TI - Detection of low numbers of bacterial cells in soils and sediments by polymerase chain reaction. AB - Polymerase chain reaction was used to amplify the low copy number of two 16S ribosomal gene fragments from soil and sediment extracts. Total DNA for polymerase chain reaction was extracted from 1 g of seeded or unseeded samples by a rapid freeze-and-thaw method. Amplified DNA fragments can be detected in DNA fractions isolated from seeded soil containing less than 3 Escherichia coli cells and from seeded sediments containing less than 10 cells. This research demonstrated that coupling polymerase chain reaction to direct DNA extraction improves sensitivity by 1 and 2 orders of magnitude for sediments and soils, respectively. This technique could become a powerful tool for genetic ecology studies. PMID- 1610202 TI - Antifungal activity of n-tributyltin acetate against some common yam rot fungi. AB - The antifungal activity of n-tributyltin acetate (TBTA) was examined in relation to combating yam rot disease. TBTA exhibited a significant effect in vitro and in vivo on four yam rot fungal isolates tested. However, the in vitro toxicity of TBTA was drastically reduced when 2.5% Tween 80 was the solvent instead of 25% acetone, as indicated by the MICs of 156.0 and 5.0 micrograms/ml, respectively. PMID- 1610203 TI - Strain selection in carbon-limited chemostats affects reproducibility of Thermoanaerobacter ethanolicus fermentations. AB - We found that the reproducibility of chemostat trials can be improved by using chemostat-adapted strains. Our experimental findings are consistent with adaptation that involves an improvement in culture fitness and an alteration of the fermentation genotype. PMID- 1610204 TI - Suitability of the prfA gene, which encodes a regulator of virulence genes in Listeria monocytogenes, in the identification of pathogenic Listeria spp. AB - The pathogenesis of listerial infections is complex and involves a number of virulence factors expressed by virulent Listeria species. We have recently described a regulator gene, prfA, that positively regulates the expression of a number of virulence factors in Listeria monocytogenes. When the prfA gene was used as a DNA probe, we found it to be extremely specific for the pathogenic species L. monocytogenes. No reaction was obtained with strains of all other species of this genus. By using this information, an oligonucleotide primer pair was developed that specifically amplifies the prfA gene in L. monocytogenes strains of all known serotypes. PMID- 1610205 TI - Toxicity of some Fusarium section Sporotrichiella strains in relation to mycotoxin production. AB - The relationship between the toxicities of crude extracts and purified toxins of Fusarium spp. belonging to the section Sporotrichiella has been assessed. Toxicity was determined on the basis of death of Artemia salina larvae and of viability and blastogenic response of bovine and human lymphocytes. Trichothecene producing strains of Fusarium sporotrichioides and Fusarium poae were toxic to A. salina and to lymphocyte blastogenesis. A strain of Fusarium tricinctum, producing visoltricin and chlamydosporol, induced differentiated activity in different bioassays (toxicity to A. salina but only minor activity against lymphocyte blastogenesis). Other, non-toxin-producing strains of Fusarium chlamydosporum, F. poae, and F. tricinctum were not active in the tested biosystems. PMID- 1610206 TI - L. monocytogenes oligonucleotide probe. PMID- 1610207 TI - Documentation of the claim that modulation of UV light pulses increases the bactericidal effectiveness of the light. PMID- 1610208 TI - Agents that cause enlargement of sebaceous glands in hairless mice. I. Topical substances. AB - We have developed a simple murine model to measure the effects on sebaceous glands of a variety of substances commonly found in topical formulations. Applications (0.2 ml) were made daily to the flanks of hairless albino female mice, for time periods varying from 4 to 9 days. Biopsies, fixed for light microscopy, were stained with H & E. Under x400 magnification, the sebocytes comprising each gland were counted, from which the mean sebocyte count per gland was calculated. Electron micrographs were prepared to evaluate sebum production. The test substances, which included anionic and cationic surfactants, solvents and emulsifiers, almost invariably led to a rapid increase in the sebocyte count, peaking at day 5. Irritating substances, such as croton oil and benzalkonium chloride, had the greatest hyperplasiogenic effect, at least doubling the sebocyte count. Electron micrographs showed large increases in rough endoplasmic reticulum and in sebum droplets. Thus, hyperplasia appears to be a stereotypic response to diverse substances, especially if these have irritancy potential. PMID- 1610209 TI - Agents that cause enlargement of sebaceous glands in hairless mice. II. Ultraviolet radiation. AB - We have developed a murine model to measure the effects on sebaceous glands of ultraviolet (UV) radiation. Hairless mice were irradiated with Westinghouse FS-40 tubes filtered to attenuate the radiation below 290 nm. Emission was mainly in the UVB range (peak, 313nm). Single and multiple exposures were given with fractions or multiples of one minimal erythemal dose (MED). Biopsies, fixed for light microscopy, were stained with H & E. Under high power, sebocytes of 30 glands per specimen were counted and the means determined. A single exposure of 1 MED caused a significant increase in sebocyte count, as did thrice-weekly exposures to 0.5 MED for 3 weeks. One 3-MED exposure produced sebocyte necrosis, yet 30 exposures at 4 MED failed to ablate the glands. In both cases there was rebound enlargement which had not returned to control levels by the end of the studies (24-30 weeks). Prolonged irradiation produced maximum enlargement in a few weeks. Thus, in a manner similar to other skin components, the response of sebaceous glands to UV radiation is one of hyperplasia. PMID- 1610210 TI - Immunohistological localization of smg p25A, a ras p21-like guanosine 5' triphosphate (GTP)-binding protein in human skin. PMID- 1610211 TI - Casein kinase II activity in psoriatic epidermis. PMID- 1610212 TI - Use of dihydrorhodamine 123 for detecting intracellular generation of peroxides upon UV irradiation in epidermal keratinocytes. PMID- 1610213 TI - Electrophoretic mobilities of keratinocytes from normal skin and psoriatic lesions. PMID- 1610214 TI - Antibacterial activity of cultured human keratinocytes. PMID- 1610216 TI - Human T lymphocytes and T-cell lines as target cells for lymphocyte chemotaxis. AB - We have observed that freshly isolated T lymphocytes from healthy donors give a chemotactic response to complement C5a in 26 of 55 individuals and to epidermal lymphocyte chemotactic factor in 15 of 23 donors using 51chromium-labelled lymphocytes in a double-filter Boyden chamber system. The reason for a lack of demonstrable chemotaxis among some cell populations is unknown, but it makes donor selection important when studying lymphocyte chemotaxis. In order to obtain a standardized screening assay for T lymphocyte chemotactic activity, we investigated a number of T-cell lines or T-cell-related cell lines such as HuT78, Jurkat, MOLT4, K562 and 1301. We observed that HuT78, K562 and Jurkat showed chemotactic responses to a variety of mediators, whereas 1301 showed chemotaxis only towards C5a, and MOLT4 was completely negative. The HuT78 cell line, which is derived from a patient with Sezary's syndrome, exhibited the highest chemotactic capacity similar to freshly isolated T lymphocytes. The only difference was its chemotactic response towards stimulation with recombinant interleukin-1 alpha and beta, which did not induce chemotaxis in human peripheral blood T lymphocytes in the Boyden chamber assay. We conclude that HuT78 can be used in screening various inflammatory mediators for their potential T lymphocyte chemotactic properties. PMID- 1610215 TI - Psoriatic skin reveals the in vivo presence of an epidermal IL-1 inhibitor. AB - Production of inhibitor(s) of IL-1 activity can be induced in keratinocytes by exposure to UVB. We describe in this study the characterization of an endogenous constitutively expressed IL-1 inhibitor which is present in extracts of human psoriatic epidermal keratome biopsies. Size-fractionated extracts of normal human epidermis did not reveal IL-1 inhibitory factor(s) activity in normal epidermis. Psoriatic epidermal extracts, however, contained virtually no IL-1 bioactivity and inhibited the activity of recombinant human IL-1 beta. This IL-1 inhibitor has a molecular weight of approximately 30 kDa and a pI of 5.3, as revealed by fast protein liquid chromatography size fractionation and chromatofocusing of psoriatic epidermal extracts. IL-1 inhibitory activity was not blocked by neutralizing anti-TGF beta monoclonal antibody. It did not have any inhibitory effect upon normal cellular proliferation but could block the IL-1 induction of IL-2 production by LBRM.33 cells as late as 4 h after exposure of LBRM.33 cells to IL-1. Thus, in vivo human psoriatic epidermis expresses an IL-1 inhibitor that specifically inhibits IL-1 activity but which appears distinct from previously described UV-induced epidermal IL-1 inhibitory activity or TGF beta. PMID- 1610217 TI - Immunohistochemical studies on NAP-1/IL-8 in contact eczema and atopic dermatitis. AB - The neutrophil activating peptide NAP-1/IL-8 has in the past been shown to be secreted by diverse cell-types involved in inflammatory processes. Furthermore, potent biological effects on both neutrophilic granulocytes and lymphocytes enforce its role in inflammation. Recently, immunohistochemical studies using monoclonal anti-NAP-1/IL-8 antibodies have been performed on dermal inflammatory conditions like psoriasis vulgaris. These have demonstrated epidermal IL-8 immunoreactivity in a pattern inversely related to the degree of inflammatory infiltration. Based on these results, in the present study biopsies from patients with contact eczema as well as atopic dermatitis were examined. The same patterns of immunoreactivity were found with either homogeneous epidermal staining, focally negative staining or overall decreased or even absent staining. As in psoriasis, these patterns were related to the degree of inflammatory infiltration. These results prove NAP-1/IL-8 to be involved not only in psoriasis vulgaris, but more likely to be a marker of different inflammatory processes. Future work will have to examine the kinetics as well as stimuli causing these effect. PMID- 1610218 TI - Infrared radiation suppresses ultraviolet B-induced sunburn-cell formation. AB - Sunburn cell (SC) formation, a quantifiable measure of epidermal cell injury induced in mouse ear skin by ultraviolet-B (UVB) radiation (290-320 nm), was significantly decreased by pre-exposure to infrared radiation (IR), which elevated the surface temperature of ear lobes to 37-42 degrees C. An autoradiographic study demonstrated that the basal cell labelling indices were significantly reduced in a surface temperature-dependent manner by pre-exposure to IR. Taken together with our previous findings that SC formation depends upon the ratio of cycling to non-cycling cells, the present findings suggest that IR retards the cell cycle and, as a result, decreases SC formation. SC counts were not altered by post-UVB exposure to IR. The effect of IR or the IR-induced increase in surface temperature should be considered when studying cutaneous damage by UVB and sunlight. PMID- 1610219 TI - Relationship between tissue reactions and morphological changes of the fungi in chromoblastomycosis: morphometry and electron microscopy. AB - To investigate the histological distribution and the morphology of the fungi and the tissue reactions in chromoblastomycosis, especially in the process of transepidermal elimination, cutaneous lesions of two patients with this disease were studied morphometrically and ultrastructurally. In the dermis, most of the fungal elements appeared as sclerotic cells and their cell wall showed an irregular, worm-eaten leaf-like appearance; they seemed to be continuously attacked by polymorphonuclear neutrophils. The epidermis eliminated 10-20% of all the organisms in the skin lesions, and the hypha-forming activity tended to be higher in the epidermis than in the dermis. Ultrastructurally, basal keratinocytes facing the dermal abscess containing fungal elements frequently appeared as dark cells, suggesting an increased proliferation activity. Spinous keratinocytes facing intraepidermal microabscesses containing fungal elements showed an abnormal accumulation of tonofilaments and further early keratinization in the spinous cell layer. All of the morphological changes of the dermis and epidermis are regarded as defence reactions against the fungi existing in the skin lesions. There is a close relationship between tissue reactions and morphological changes of fungi in chromoblastomycosis. PMID- 1610220 TI - Intraaortic balloon counterpulsation: patterns of usage and outcome in cardiac surgery patients. AB - Between January 1, 1986, and May 6, 1991, 7,884 cardiac surgical procedures requiring cardiopulmonary bypass were performed at our institution, including 672 (9.8% of adult procedures) performed in 669 patients that were associated with preoperative (n = 240), intraoperative (n = 353), or postoperative (n = 79) use of an intraaortic balloon pump. The mean age of recipients was 65.3 years (range, 16 to 89 years). Intraaortic balloon pump usage increased during the study period from 6.4% of patients (83/1,298) in 1986 to 12.7% of patients (169/1,333) in 1990. The relative distribution between preoperative (mean, 35.7%), intraoperative (52.5%), and postoperative (11.8%) insertion remained nearly constant during the study period. The overall operative (30-day) mortality for patients with preoperative, intraoperative, or postoperative insertion of the intraaortic balloon pump was 19.6%, 32.3%, and 40.5%, respectively (X2 = 16.4; p less than 0.001). Although use of the intraaortic balloon pump in the intraoperative and postoperative settings is accompanied by a favorable outcome in most patients, the high associated mortality suggests the need for earlier use of the intraaortic balloon pump or other supportive measures such as the ventricular assist device. PMID- 1610221 TI - Ionescu-Shiley valve failure. I: Experience with 125 standard-profile explants. AB - A group of standard-profile Ionescu-Shiley valve implants, 357 aortic and 190 mitral, was reviewed for cases of failure requiring surgical explantation. To date, 90 (25.2%) of the aortic and 35 (18.4%) of the mitral valves have failed, and are the subject of this analysis. Observations of these explants confirm previous suggestions about the clinical and pathologic patterns of the Ionescu Shiley valve's failure, but are extended in this study to allow more confident statistical analyses. Cusp tear with insufficiency remains the most important reason for explantation, precipitating removal to date of 19.1% of the aortic and 10.0% of the mitral valves implanted. This difference, aortic versus mitral, is significant (p less than 0.006) and the reverse of observations made in other studies of pericardial valves. In this review there is no significant difference in the proportion of aortic and mitral valves that failed with calcification (2.2% and 3.1%, respectively). Aortic Ionescu-Shiley valves failing with tears had a mean of 3.1 tears per valve, whereas mitral valves had 1.2. Aortic valves also showed considerably more pretear wear than did mitral valves. Although the large number of these Ionescu-Shiley valve failures has been a profound clinical disappointment, it has provided an opportunity to observe and detail the pathology of their failure. PMID- 1610222 TI - Ionescu-Shiley valve failure. II: Experience with 25 low-profile explants. AB - A group of patients who had low-profile Ionescu-Shiley valves implanted, 237 aortic and 130 mitral, was reviewed for cases of bioprosthetic failure requiring explantation. Fourteen such aortic and 11 mitral valves were recovered at operation. The most common reason for explantation was valvular insufficiency due to cusp tears, accounting for 50.0% of aortic and 82.0% of mitral explants. Morphologic examination of the valves suggested a common mode of failure with tears, and this is illustrated. The clinical and pathologic patterns of this valve's failure are compared with those of the standard-profile Ionescu-Shiley valve, and many similarities exist. A tendency for a larger proportion of mitral valve failures with tears is, however, in contrast to observations of the standard-profile valve, in which aortic failures are more common. Additionally, low-profile valves, in either the aortic or mitral positions, fail after a shorter time in situ than their standard-profile counterparts, at a mean of 45.1 months versus 78.0 in the aortic position (p less than 0.01) and at 52.2 months versus 73.8 in the mitral position (p less than 0.05). These differences in the performance of the Ionescu-Shiley valve models may have implications for the design of future bioprostheses. PMID- 1610224 TI - Surgical implications of juxtaposed atrial appendages and the associated anomalies. AB - Juxtaposition of the atrial appendages (JAA) is an uncommon anomaly of the heart that is frequently associated with other cardiac abnormalities, such as transposition of the great arteries and tricuspid atresia. We encountered 7 patients with JAA from July 1984 to July 1989 at National Taiwan University Hospital. The JAA was right-sided in 1 patient and left-sided in 6. The patients' ages ranged from 10 months to 12 years. The cardiac anomalies in the patient with right JAA were double-outlet right ventricle and ventricular septal defect, which was repaired with a patch. Of the 6 patients with left JAA, 5 had transposition of the great arteries, and in 3 of them obstructive tricuspid lesions (tricuspid stenosis in 1, tricuspid atresia in 2) were noted. Three patients with left JAA and normal tricuspid valve underwent total correction (one Senning operation and two Rastelli operations). The other 3 patients with tricuspid obstruction underwent total cavopulmonary connection (2) and Fontan operation (1). We concluded that, first, left JAA was more frequently seen and associated with more morbid anatomy than right JAA. Second, if left JAA is discovered in planning biventricular repair for transposition of the great arteries, the tricuspid valve should be inspected carefully to rule out tricuspid obstruction. PMID- 1610223 TI - Myocardial protection of neonatal heart by cardioplegic solution with recombinant human superoxide dismutase. AB - The effectiveness of high-potassium cardioplegic solution in the neonatal heart remains controversial. Our previous study indicated that the protection afforded by a cardioplegic solution was inadequate in the neonatal heart. On the hypothesis that oxyradicals were responsible for the ineffectiveness of cardioplegic solution in neonatal heart, the effects of a cardioplegic solution (a modified St. Thomas' Hospital cardioplegic solution) with recombinant human superoxide dismutase on the isolated perfused neonatal guinea pig hearts (within 2 days after delivery, body weight of 60 to 120 g) were studied in comparison with those on the adult hearts (6 to 8 weeks after delivery, body weight of 300 to 500 g). After arrest induced by modified St. Thomas' Hospital cardioplegic solution, hearts were subjected to 120 min of ischemia at 20 degrees C, during which time the cardioplegic solution was injected every 30 minutes. Then the heart was reperfused for 60 minutes at 37 degrees C. Under this condition, the left ventricular developed pressure recovered to 84.4% +/- 4.0% of the preischemic value in the adult heart, whereas the recovery was only 68.1% +/- 3.1% in the neonatal heart. Thiobarbituric acid-reactive substance level, a parameter of lipid peroxidation by oxyradicals, significantly increased during ischemic arrest both in the adult and neonatal heart. However, the increase was much greater in the neonatal heart than in the adult. Cardioplegia with recombinant human superoxide dismutase (300 and 1,000 U/mL) significantly inhibited this accumulation of thiobarbituric acid-reactive substance in the neonatal heart; at 1,000 U/mL, the myocardial function of the reperfused neonatal heart recovered to the level of the adult heart.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610225 TI - Coarctation repair in neonates with subclavian-sparing advancement flap. AB - A modification of the technique of using the subclavian-sparing advancement flap for severe coarctation of the aorta was successfully used in 7 neonates ranging in age from 3 to 30 days (mean age, 12 days). Four of the 7 patients had associated cardiac defects with congestive heart failure. The procedure was performed through a left thoracotomy incision, and the coarctation repair was performed by advancing the origin of the left subclavian artery as a flap while preserving flow to the left arm. No deaths occurred, and there was patency of the repair in all patients at follow-up ranging from 1 1/2 to 2 1/4 years (mean, 2 years). In 7 of the 8 patients there was no clinically significant gradient either by examination or Doppler echocardiography at follow-up. One patient underwent balloon angioplasty at the time of catheterization to evaluate other cardiac defects 1 year postoperatively, at which time he was noted to have a peak systolic gradient of 30 mm Hg across the repair site. The technique of subclavian sparing advancement is a reasonable addition to the surgical armamentarium for coarctation repair in neonates. It provides the advantages of subclavian flap aortoplasty without sacrificing the blood supply to the left arm. Because of the unique anatomic variations associated with coarctation of the aorta, we suggest that the choice of repair be individualized for patients with this condition. PMID- 1610226 TI - Thoracoscopic resection of an anterior mediastinal tumor. AB - The therapeutic role of thoracoscopy has expanded with advances in endoscopic surgical instrumentation and laser technology. We report a complete thoracoscopic resection of an encapsulated (stage I) thymoma with lymphocytic predominance in an elderly woman without myasthenia gravis. The patient had an uncomplicated postoperative course and was discharged on the third postoperative day. Median sternotomy with its attendant morbidity was avoided. Thoracoscopic resection of thymic neoplasms may be a useful approach in carefully selected patients. PMID- 1610227 TI - Intercostal hemangioma presenting as a chest wall tumor. AB - Skeletal muscle hemangiomas are uncommonly described in a variety of locations. This report details the diagnosis and management of a 39-year-old woman with a right chest wall mass detected on physical examination. After a negative diagnostic evaluation, exploratory thoracotomy revealed an intercostal hemangioma, undescribed in recent literature. The lesion was excised. PMID- 1610228 TI - Carbon dioxide prevents pulmonary overcirculation in hypoplastic left heart syndrome. AB - Circulatory and metabolic homeostasis in patients with hypoplastic left heart syndrome is dependent on a delicate balance between systemic and pulmonary blood flow. Hypocarbia can result in a marked decrease in pulmonary vascular resistance accompanied by pulmonary overcirculation, systemic hypotension, metabolic acidosis, and death. This report illustrates that early and precise control of the arterial carbon dioxide tension using inspired carbon dioxide can be effective in preventing or treating instability arising during management of a patient with hypoplastic left heart syndrome. PMID- 1610229 TI - Early structural deterioration with the mitroflow pericardial xenograft in the mitral position. AB - Early structural deterioration with the mitral Mitroflow pericardial valve requiring reoperation occurred in 6 patients. Clinical diagnosis of prosthetic failure was made 5 to 58 months after valve implantation (mean, 38 months). Re replacement was carried out 22 to 80 months (mean, 55 months) after the initial operation. Mode of failures were cuspal tear without calcification in three valves and massive calcifications in the remaining bioprostheses. High incidence of early structural deterioration of the Mitroflow pericardial valve makes this new prosthesis an unsatisfactory alternative as a substitute in the mitral position. PMID- 1610230 TI - Aortoesophageal fistula induced by foreign bodies. AB - Two patients with aortoesophageal fistula induced by foreign bodies were surgically treated during a period of 10 years. The first patient was surgically treated through a right thoracotomy, which failed on account of exsanguination. In the second patient, a Sengstaken-Blakemore tube was inserted for esophageal tamponade. The aorta was successfully repaired through a left thoracotomy after occlusion of the esophagus and the aorta above and below the fistula. Therefore, we recommend preoperative esophageal tamponade and occlusion of the esophagus and the aorta through a left thoracotomy as the most successful approach. PMID- 1610231 TI - Combined traumatic avulsion of the aortic valve and rupture of the left common carotid artery. AB - A case of complete rupture of the left common carotid artery at the aortic arch and avulsion of a cusp of the aortic valve due to blunt trauma is presented. The ruptured carotid artery was reimplanted into the left subclavian artery, and the avulsed aortic valve cusp was successfully repaired by direct suturing. PMID- 1610232 TI - Central cyanosis due to prominence of the eustachian and thebesian valves. AB - A 9-year-old female child with serious central cyanosis was found to have right to left shunt across a large secundum atrial septal defect despite normal right sided pressures. Preoperative cross-sectional echocardiography suggested the presence of large sinus venosus eustachian and thebesian valves as the mechanism responsible for diversion of the inferior caval and coronary sinus venous return to the left atrium across the interatrial secundum defect. Surgical excision of the unduly prominent sinus venosus valve and patch closure of the atrial septal defect resulted in complete disappearance of the cyanosis and physiological and clinical cure. PMID- 1610233 TI - Perfusion of dominant left subclavian artery during thoracic aortic aneurysm operation. AB - A case of aneurysm of the descending thoracic aorta with dominant left vertebral artery and poor cross-collateral circulation is reported. We believe that in such a patient perfusion of the dominant left subclavian artery is a safe method to prevent vertebrobasilar ischemia during thoracic aortic aneurysm operation under normothermia. PMID- 1610234 TI - Simplified muscle-sparing thoracotomy for patent ductus arteriosus ligation in neonates. AB - To reduce operative morbidity we have developed a simplified muscle-sparing thoracotomy that provides excellent exposure for patent ductus arteriosus ligation in neonates. Operative time has not increased and seroma formation has not occurred. Improved functional and cosmetic results as well as less postoperative pain may be obtained by preserving the latissimus dorsi and serratus anterior muscles. PMID- 1610235 TI - Esophagogastrectomy and the variant left hepatic artery. AB - A variant left hepatic artery occurs at a rate of approximately 10%. In standard esophagogastrectomy and some proximal gastric operations this variant artery is sacrificed, which has led to reported fatalities secondary to hepatic necrosis. We report our method of esophagogastrectomy in the presence of an aberrant left hepatic artery. PMID- 1610236 TI - Damus-Stansel-Kaye procedure: technical modifications. AB - The Damus-Stansel-Kaye procedure has been applied for the relief of outflow tract obstruction caused by a restrictive bulboventricular foramen or subaortic stenosis in patients with complex univentricular heart disease. The procedure may also be part of a biventricular repair of a Taussig-Bing transposition of the great arteries. This report details technical modifications of the procedure to ensure unobstructed blood flow from the pulmonary artery to the aorta and to maintain the integrity of the pulmonary and aortic valves. PMID- 1610237 TI - Subfascial implantation of implantable cardioverter defibrillator generator. AB - The automatic cardioverter defibrillator generator is a relatively large unit, which has most often been implanted in a subcutaneous pocket. In a consecutive series of 120 primary implantations, we employed a subrectus fascia pocket that has resulted in a cosmetically superior result with a 0.8% incidence of system infection. The technique of subfascial implantation is described. PMID- 1610238 TI - Mechanical support for intraventricular decompression in repair of left ventricular disruption. AB - Posterior disruption of the left ventricle is a difficult injury to repair and is associated with a high intraoperative mortality. We report a case of posterior disruption that occurred during a mitral valve operation. A conventional approach to repair failed after sutures tore through the myocardium. Intraventricular decompression to reduce ventricular wall tension and allow for successful suture repair of the injury was accomplished by insertion of a BioMedicus left ventricular assist device. PMID- 1610239 TI - Rupture of the airways from blunt trauma: treatment of complex injuries. AB - Tracheobronchial rupture from blunt trauma is usually single and transverse but may be longitudinal or complex, a combination of various sites and forms of rupture. From 1970 to 1990, 183 cases of rupture of the airways were reported in the literature: 136 (74%) transverse, 33 (18%) longitudinal, and 14 (8%) complex. During the same 20 years at Grady Memorial Hospital, 6 patients with such injuries were treated. One had complex injury consisting of rupture of the distal trachea and both main bronchi, 1 had a longitudinal tracheal rupture and rupture of the innominate artery, and 4 had a transverse rupture, 1 of whom also had a traumatic false aneurysm of the left pulmonary artery. Cardiopulmonary bypass was used only for the repair of the complex injury, whereas the repair of the left main bronchial rupture associated with a false aneurysm of the left pulmonary artery was done with standby cardiopulmonary bypass. All 6 patients had satisfactory results from the correction of their lesions except 1 child in whom stenosis developed at the rupture site. This study suggests that complex injuries are rarely seen, and their repair is often quite involved. In some of these cases, the use of cardiopulmonary bypass increases the margin of safety during operation and may encourage repair rather than resection of the affected lung. PMID- 1610240 TI - Physician payment reform: a bibliography. PMID- 1610241 TI - Total orthotopic heart transplantation: an alternative to the standard technique. PMID- 1610242 TI - A new idea. PMID- 1610243 TI - Rereplacement of the mitral valve with represervation of the subvalvular apparatus. PMID- 1610244 TI - Modified technique of internal mammary artery harvest. PMID- 1610245 TI - Ischemic mitral valve repair. PMID- 1610246 TI - Acute pulmonary edema in closed mitral commissurotomy. PMID- 1610248 TI - Lobectomy without a rib spreader. PMID- 1610249 TI - Double-lung transplantation for cystic fibrosis. The Cystic Fibrosis Transplant Study Group. AB - One hundred twenty cystic fibrosis patients were accepted for transplantation. Twenty-five patients underwent double-lung transplantation. Twenty-five patients died awaiting transplantation (20.6%). There were 13 female and 12 male patients. Their mean age was 28 years (range, 7 to 34 years), and mean percentage ideal body weight was 76% (range, 58.5% to 91.9%). Most patients were hypoxic and hypercarbic. Two patients underwent tracheal anastomosis, 15 had en bloc bronchial anastomoses, and 8 had sequential single-lung transplants. Operative mortality was 16%; all deaths were related to bleeding from extensive adhesions. Actuarial survival at 1 year was 64%. Rejection and infection were frequent during the first month and decreased thereafter. Airway complications occurred in 5 patients but were amenable to laser therapy and stenting. We conclude that double-lung transplantation is an acceptable modality for the treatment of cystic fibrosis patients with end-stage lung disease. It may be a better alternative to heart-lung transplantation considering the paucity of thoracic organ donors. PMID- 1610247 TI - Pericardial window. PMID- 1610250 TI - Resectional management of thyroid carcinoma invading the airway. AB - Fifty-two patients had thyroid carcinoma invading the airway. Thirty-four underwent resection; 18 were male and 16 female. Age ranged from 17 to 79 years. Twenty-seven had resection with airway reconstruction (1 wedge excision, 10 sleeve tracheal resections, 6 tracheal resections with a portion of the cricoid cartilage, and 10 complex laryngotracheoplastic resections). Seven required cervicomediastinal exenteration with mediastinal tracheostomy; 3 of these had esophagectomy with colon interposition. Nineteen tumors were papillary, 6 follicular, 4 mixed papillary and follicular, 1 squamous, 2 undifferentiated giant cell, 1 anaplastic spindle cell carcinoma, and 1 carcinosarcoma. Three postoperative deaths occurred. Thirteen of the 31 survivors died of cancer from 1/4 to 10 1/4 years postoperatively (average, 4.4 years). Four died of other diseases. Fourteen are alive from 1/12 to 14 1/3 years postoperatively (average, 5.3 years). Only 2 patients had airway recurrence. Resection of the airway invaded by thyroid malignancy in the absence of extensive metastases offers prolonged palliation, avoids suffocation due to bleeding or obstruction, and may produce cure. Airway reconstruction should be performed whenever technically feasible. PMID- 1610251 TI - Renal cell carcinoma: resection of solitary and multiple metastases. AB - Between 1985 and 1991, 23 patients underwent resection of pulmonary metastases from renal cell carcinoma, of whom 18 had previously received interleukin-2 based immunotherapies. Mean survival from exploration in all patients was 43 months. Survival after resection did not correlate with the number of nodules on preoperative tomograms, the number of nodules resected, or the disease-free interval. Patients who underwent complete resection of metastatic disease (n = 15), however, had a significantly longer survival (mean, 49 months; median not yet achieved) compared with patients with incomplete resection (median, 16 months) (p2 = 0.02). Two of the 15 patients who underwent curative resections are presently free of disease greater than 45 months after exploration. These data support surgical resection of isolated pulmonary metastatic disease from renal cell cancer. PMID- 1610252 TI - Magnetic resonance imaging evaluation of recipient for cryopreserved aortic allograft. AB - Aortic valve replacement with a cryopreserved aortic allograft is the procedure of choice for many patients with aortic valvular heart disease. We have used magnetic resonance imaging preoperatively to determine annular size and coronary artery orientation in the recipient, which not only has enabled us to select an allograft of appropriate size from a distant tissue bank, but also has helped us to identify preoperatively the recipient with a truly bicuspid valve in which the coronary arteries are oriented 180 degrees apart. Sixteen consecutive patients were evaluated preoperatively, the aortic annulus being measured with both magnetic resonance imaging and echocardiography. Cryopreserved aortic allografts were ordered on the basis of the magnetic resonance imaging measurement. Annular size was then measured intraoperatively with calibrated sizers. Magnetic resonance imaging annular measurements correlated highly with those found at operation (r = 0.92), whereas echocardiographic measurements correlated less well (r = 0.69). Coronary orientation was accurately predicted in every case (r = 1.0). Therefore, we have found magnetic resonance imaging to be useful in the preoperative evaluation of patients for aortic valve replacement with a cryopreserved aortic allograft. PMID- 1610253 TI - Usefulness of right ventricular indices in early diagnosis of cardiac tamponade. AB - Early diagnosis of postoperative cardiac tamponade is impeded by its clinical similarity to left ventricular failure. Moreover, the hemodynamic changes necessary to diagnose cardiac tamponade are detected by conventional monitoring technique only after clinical compromise. Early signs of cardiac tamponade and left ventricular failure were studied with emphasis on right ventricular function in anesthetized dogs. One group (n = 20) had cardiac tamponade produced by incrementally increasing pericardial pressure (2 to 20 mm Hg), and another group (n = 20) had acute left ventricular failure produced by successive ligation of the anterior descending coronary artery at the lower, middle, and upper thirds. Besides standard hemodynamic measurements, right ventricular function was examined with a rapid-response thermodilution catheter. During cardiac tamponade, cardiac output, right ventricular ejection fraction, right ventricular stroke volume, and right ventricular end-diastolic volume were significantly decreased from baseline values after a pericardial pressure of 8 mm Hg or more (p less than 0.05). Right atrial and pulmonary arterial pressures were not significantly elevated until 14 and 20 mm Hg of pericardial pressure, respectively. Although cardiac function in the left ventricular failure group was reduced after each ligation, right ventricular ejection fraction remained unchanged. This study suggests that right ventricular indices may facilitate earlier diagnosis of cardiac tamponade with greater accuracy. PMID- 1610254 TI - Bronchial carcinoid tumors: a retrospective analysis of 126 patients. AB - From 1970 until 1990, 8,958 cases of primary carcinoma of the lung were diagnosed at the Duke University Medical Center. During the same period, 126 patients (mean age, 53 +/- 13 years) were diagnosed with bronchial carcinoid. The overall survival was 78% for 5 years and 71% for 10 years. Surgical treatment in 106 patients included pneumonectomy (15), lobectomy (63 with 9 bronchoplastic procedures), stapled wedge resection (22), and bronchoscopic laser resection (6). The method of diagnosis was chest roentgenography (121), chest computed tomography (77), mediastinal tomography (31), bronchoscopy (81), bronchoscopic brushing and washing (50), bronchoscopic biopsy (40), transthoracic needle biopsy (27), thoracotomy (100), and autopsy (5). Univariate analysis of the medical history, presenting signs and symptoms, diagnostic test results, and pathologic data predicted improved survival (p less than 0.001) for: female sex (n = 58), asymptomatic presentation (n = 47), normal serum serotonin or urinary hydroxyindoleacetic acid levels (n = 76), peripheral location of the primary tumor (n = 50), pathologic stage I or II (n = 91), negative lymph nodes (n = 80), primary tumor 2 cm or less in diameter (n = 67), and typical histology (n = 80). No significance (p greater than 0.1) was observed for age, smoking history, race, family history of carcinoid, environmental exposure, or hemoptysis. The most important factors affecting survival defined by multivariate analysis were (p less than 0.01) pathologic stage, atypical histology, and asymptomatic presentation. Bronchial carcinoid tumors are unique, making up 1% to 2% of primary lung neoplasms and having an excellent prognosis after resection with a 95% 5-year and 93% 10-year survival for pathologic stage I disease. PMID- 1610255 TI - Retrograde versus antegrade cardioplegia: impact on right ventricular function. AB - Retrograde cardioplegia administered through the coronary sinus has several documented advantages over antegrade cardioplegia but has been thought to provide inadequate right ventricular myocardial protection. We prospectively compared the effects of retrograde and antegrade cardioplegia on right ventricular performance in patients undergoing myocardial revascularization. Two groups of similar age, extent of disease, and preoperative left ventricular ejection fraction received retrograde (n = 16) or antegrade (n = 14) crystalloid cardioplegia. A right ventricular rapid-response thermistor catheter, previously developed and validated in our institution, was used to measure right atrial pressure, pulmonary artery pressure, right ventricular ejection fraction, end-diastolic volume index, and stroke volume index before bypass (baseline) and at several intervals after bypass. There were no differences in cross-clamp time, heart rate, cardiac enzymes, inotrope requirements, or arrhythmias between the two groups. Right ventricular parameters were equivalent in both groups at all time intervals except 30 minutes after bypass, at which time right ventricular end diastolic volume index was lower (80 +/- 6 versus 93 +/- 6 mL/m2; p less than 0.05) and right ventricular stroke volume index was higher (35 +/- 3 versus 29 +/ 2 mL/m2, p less than 0.05) in the retrograde group compared with the antegrade group, indicating better right ventricular function with retrograde cardioplegia early after bypass. In both groups, right ventricular end-diastolic volume index was higher than baseline (p less than 0.05) during the first 4 hours after bypass. No other important differences were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610256 TI - Combined conventional mechanical and ultrasonic debridement for aortic valvular stenosis. AB - Ultrasound decalcification of aortic valve stenosis was performed in 31 patients. There were 16 men and 15 women with a mean age of 71.03 +/- 9.6 years (range, 51 to 89 years). Each had severe calcific aortic stenosis with an aortic valve gradient greater than 40 mm Hg, aortic valve area (AVA) less than 0.6 cm2, and no serious insufficiency. Feasibility of aortic valve debridement was determined under direct vision. Intraoperative epicardial or transesophageal color Doppler two-dimensional echocardiography was used before and after the aortic valve debridement to evaluate aortic cusp motion and aortic regurgitation. Direct transseptal aortic valve gradient was measured on all patients before and after aortic valve debridement, and the AVA was determined. Aortic valve debridement was performed as the primary procedure in 17 cases and combined with other cardiac procedures in 14 patients. Preoperative aortic valve gradient was reduced from 72.5 +/- 22.5 mm Hg (range, 40 to 130 mm Hg) to 15.5 +/- 11.9 mm Hg (range, 2 to 50 mm Hg), and the average AVA of 0.41 +/- 0.10 cm2 (range, 0.22 to 0.63 cm2) was increased to 1.55 +/- 0.58 cm2 (range, 0.65 to 3.50 cm2) after ultrasound decalcification. There were two early deaths in octogenerian, high risk patients, and two late deaths (6.45% early and 6.45% late mortality), none of them related to AVD. Postoperative follow-up included clinical evaluation and color Doppler echocardiography every 6 months. The aortic valve gradient was measured using a continuous-wave Doppler probe, and the AVA was calculated by the simplified continuity equation: AVA = aAOA x vLVOT/vAV.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610258 TI - Spinal oxygenation, blood supply localization, cooling, and function with aortic clamping. AB - Similar to other methods of organ preservation, "spinoplegia" may protect the spinal cord from the effects of oxygen desaturation during aortic cross-clamping. In porcine experiments, spinal cord O2 saturation was studied during intraoperative localization of the blood supply to the spinal cord using hydrogen; division of arteries not supplying the spinal cord; aortic cross clamping for 60 minutes; and 60 minutes after unclamping. In 5 animals, 120 mL of cold saline solution with lidocaine (100 mg/dL) was infused into the aorta during aortic cross-clamping. During sequential localization, O2 saturation dropped by 40.02% (standard deviation, 20.16%) for T-14 artery testing versus a decrease of 17.27% (standard deviation, 11.88%; p = 0.0075) for L-5 artery segment testing in the control animals and returned to baseline thereafter. During aortic cross clamping maximal O2 desaturation was 5% of baseline (15.7%; p less than 0.0001), which improved slightly by 30 minutes after clamping (48% of baseline +/- 37.37%; p = 0.048 versus maximum) and then returned to baseline (97.1% of baseline +/- 41%) with unclamping; 5 minutes later, hyperoxygenation occurred with a progressive decline thereafter (68% of baseline +/- 29.3%; p = 0.025, 45 minutes after unclamping versus baseline). The decrease in spinal motor evoked potentials was significantly less (p less than 0.02) in the treated group. Intraoperative hydrogen testing in 8 patients was demonstrated to be safe. It accurately localized reattached arteries, and O2 saturation of the spinal cord fell by 56% (standard deviation, 29%; p = 0.0025) with aortic cross-clamping. We conclude that spinal cord ischemia occurs with aortic cross-clamping in both animals and humans.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610257 TI - Mitral valve replacement: randomized trial of St. Jude and Medtronic-Hall prostheses. AB - To better define the merits of the bileaflet and tilting-disc valves, we prospectively randomized 102 patients (mean age, 57 years; range, 11 to 85 years) to receive either the St. Jude (n = 55) or the Medtronic-Hall (n = 47) mitral valve prosthesis between September 1986 and May 1991. The two groups were not different with respect to preoperative New York Heart Association class, incidence of mitral stenosis and insufficiency, angina score, extent of coronary artery disease, ventricular function, completeness of revascularization, or cross clamp or bypass time. The hospital mortality (14.5% versus 10.6%, St. Jude versus Medtronic-Hall) and late mortality (7.3% versus 2.1%) were not significantly different. Follow-up was complete in 84 of 89 hospital survivors (94%) with a mean of 26 months (range, 1 to 60 months). The linearized rates of valve-related events and the 3-year actuarial survival demonstrated no significant differences between both cohorts. Comparison of the clinical outcome and echocardiographic parameters obtained at the time of follow-up demonstrated no significant differences between the two prostheses. These data indicate that the Medtronic Hall and St. Jude mitral prostheses are similar with respect to their rates of valve-related complications and hemodynamic profiles. This study suggests that there is no difference between the St. Jude and Medtronic-Hall prostheses with regard to early clinical performance or hemodynamic results and therefore does not support the preferential selection of either prosthesis. PMID- 1610259 TI - Elective pneumonectomy: factors associated with morbidity and operative mortality. AB - We have retrospectively reviewed hospital records of 197 consecutive patients undergoing pneumonectomy for neoplastic disease between 1985 and 1990 to identify predictors of outcome. Seventeen of the 197 patients died during their hospital stay (8.6%; 95% confidence intervals, 6.7% to 11.2%). The most significant predictors of in-hospital mortality were presence of coexisting medical conditions (p less than 0.001), respiratory function tests showing an obstructive picture with a forced expiratory volume in 1 second/forced vital capacity ratio of less than 0.55 (p less than 0.001), 24-hour fluid replacement of more than 3 L (p less than 0.05), postoperative pulmonary edema (p less than 0.001), respiratory tract infection with positive sputum culture (p less than 0.01), postoperative renal failure (p less than 0.001), and cardiac arrhythmias (p less than 0.001). There were 232 postoperative management, problems occurring in 197 patients. The most significant predictors of postoperative morbidity were continued cigarette smoking up to the time of operation (p less than 0.05), perioperative blood loss or more than 2 L (p less than 0.05), and infusion of more than 3 L of fluid in the first 24 hours (p less than 0.05). Although retrospective analyses must be interpreted with caution, this study has identified preoperative and perioperative factors associated with in-hospital morbidity and mortality after pneumonectomy. PMID- 1610260 TI - Mitral valve repair in patients with endomyocardial fibrosis. AB - Between 1987 and 1990, 12 patients were operated on for endomyocardial fibrosis at our institution. Nine were treated by endocardectomy and mitral valve repair and constitute the material of this study. Ages ranged from 9 to 58 years (mean age, 32.5 years). Biventricular involvement was present in 3 cases, and 6 patients had predominantly left ventricular endomyocardial fibrosis. Six patients were in New York Heart Association class III/IV. Six patients had severe mitral insufficiency (3 to 4/4) and 3 patients had moderate mitral insufficiency (2/4). The operation consisted of left ventricular endocardectomy with complete detachment and mobilization of the posterior leaflet of the mitral valve in all cases. An autologous pericardial patch was used to reconstruct posterior leaflet continuity in 4 patients. In 7 patients a prosthetic mitral ring was used. In 3 patients right ventricular endocardectomy and tricuspid valve repair were also performed. All patients survived and none required early reoperation. Follow-up was complete and ranged from 9 to 38 months. No late deaths occurred, and 1 patient required mitral valve replacement for recurrent mitral regurgitation. Doppler echocardiographic studies were performed in 7 patients and revealed no or mild mitral insufficiency. In conclusion, mitral valve repair is safe and offers good early and late results in patients with endomyocardial fibrosis. PMID- 1610261 TI - Acadesine (AICA-riboside) improves postischemic cardiac recovery. AB - To test if acadesine (5-aminoimidazole-4-carboxamide riboside), a purine precursor, has cardioprotective effects, 16 dogs were placed on total cardiopulmonary bypass and subjected to global myocardial ischemia. Hemodynamic recovery was compared between a control (n = 8) group receiving standard cardioplegia and an acadesine (n = 8) group pretreated with intravenous acadesine (2.5 mg.kg-1.min-1 for 5 minutes, then 0.5 mg.kg-1.min-1) before ischemia, during ischemia, and until 10 minutes after removal of the aortic cross-clamp. Additionally, in the acadesine group the cardioplegia also contained 20 mumol/L acadesine. While the dogs were on cardiopulmonary bypass, global warm myocardial ischemia was induced by aortic cross-clamping for 5 minutes under normothermic conditions to simulate an angioplasty accident. Five minutes after aortic cross clamping, hypothermic cardioplegia (30 mL/kg) was administered. The left anterior descending coronary artery was occluded before the first infusion of cardioplegia to simulate poor cardioplegia delivery that can occur during an emergency coronary artery bypass procedure after an angioplasty accident. The left anterior descending artery occlusion was released, and additional cardioplegia (15 mL/kg) infusions were made every 30 minutes thereafter during 120 minutes of cardioplegic ischemia. Thirty minutes after reperfusion, all animals in both groups were weaned from bypass and recovery data were obtained to compare with baseline preischemic values. There were no significant differences in heart rate, left atrial pressure, or systemic vascular resistance between groups after weaning from bypass. Peak developed pressure recovered to 79% +/- 19% (mean +/- standard deviation) of baseline in the acadesine group compared with 56% +/- 22% in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610262 TI - Primary lung cancer in young patients: a study of 82 surgically treated patients. AB - The aim of this study was to evaluate the prognosis for surgically treated young patients with primary lung cancer, a prognosis generally considered to be very poor. Eighty-two patients less than 40 years of age were operated on at Marie Lannelongue Hospital between 1982 and 1990. There were 72 male and 10 female patients. Ten patients (12%) had never smoked, whereas 48 patients (59%) had smoked for more than 20 pack-years. The lung cancer was asymptomatic in 27 patients (33%) and symptomatic in the others. Adenocarcinoma was found in 42% of the patients, epidermoid carcinoma in 28%, mixed cell carcinoma in 16%, small cell carcinoma in 8.5%, and undifferentiated large cell carcinoma in 6%. Among the 69 resected tumors, 22 were stage I, ten were stage II, 32 were stage IIIa, and five were stage IIIb. The resection was considered complete and curative in 56 patients (68%) and noncurative in 26 (32%) either because of an incomplete resection (12 in stage IIIa; 1 in stage IIIb) or because of an exploratory thoracotomy only (13). The overall actuarial 5-year survival rate was 41%, and the actuarial 5-year survival for patients who had a complete resection was 56%. The actuarial 5-year survival rates were as follows: patients in stage I, 70%; stage II, 54%; stage IIIa, 28%; stage IIIb, 0%; and patients having exploratory thoracotomy only, 18%. These survival rates are similar to those of patients older than 40 years with similar stages of disease.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610263 TI - Distribution of cholecystokinin octapeptide in the cat brainstem: an immunocytochemical study. AB - Using an indirect immunoperoxidase technique, the cell bodies and fibers containing cholecystokinin octapeptide in the brainstem of the cat were located. A high density of immunoreactive perikarya was observed in the lateral tegmental field and retrorubral nucleus, whereas a moderate density was found in the nucleus incertus, periaqueductal gray and dorsal tegmental nucleus. The nuclei coeruleus, sagulum, interpeduncular, motor dorsal nucleus of the vagus and nucleus of the solitary tract had a low density of immunoreactive cell bodies. The densest network of immunoreactive fibers was observed in the interpeduncular nucleus. The nuclei coeruleus, sagulum, praepositus hypoglossi, cuneiform, dorsal and ventral nuclei of the lateral lemniscus, marginal nucleus of the brachium conjunctivum, dorsal motor nucleus of the vagus, lateral tegmental field, inferior colliculus, periaqueductal gray and nucleus of the solitary tract had a moderate density of immunoreactive fibers. Finally, scarce immunoreactive fibers were found in the nucleus of the brachium of the inferior colliculus, inferior central nucleus, nucleus incertus, retrorubral nucleus and dorsal tegmental nucleus. PMID- 1610264 TI - Calbindin D-28K in the nucleus pretectalis superficialis parvicellularis of Salmo gairdneri: an immunocytochemical study. AB - The distribution of calbindin D-28K (CaBP28K) cell bodies and fibers in the nucleus pretectalis superficialis parvicellularis of the rainbow trout was studied using a monoclonal antibody and the avidin-biotin-peroxidase method. In this diencephalic nucleus a very high density of CaBP28K immunoreactive fibers was found. In addition, a high density of CaBP28K positive neurons was also observed. These neurons were small, showing one, two or three short and non branching dendritic trunks. The distribution and orientation of the immunoreactive cell bodies in the nucleus pretectalis superficialis parvicellularis suggests that the neurons might be interneurons and/or projecting neurons. PMID- 1610265 TI - Organized variability in the neuromuscular system: a survey of task-related adaptations. AB - This survey concerns the physiology of the neuromuscular system, as studied at the level of the single mammalian limb muscle and its motoneurones (MNs). Particular attention is devoted to the ways in which the properties and the organization of spinal MNs are adapted for the control of muscle (unit) force. These questions are discussed in relation to: a) The general and basic task of the system: providing a smooth and finely gradeable force by the mechanisms of rate- and recruitment-modulation of MN activity. b) Gradation problems in relation to specific peripheral requirements in connection with: (i) tasks of different duty-time (i.e. problems related to fatigue and endurance); (ii) tasks of different speed; (iii) task using different muscle lengths; (iv) tasks requiring different adjustment-gains. c) The adaptational properties of the neuromuscular system as it is subjected to long-term changes in its motor tasks. These matters are largely discussed in relation to experiments for studying the responses of the neuromuscular system to different patterns of chronic electrical stimulation. d) The manner in which the neuromuscular system, at the level of a single unidirectional muscle, is used for different motor programs. Evidence is summarized which shows the presence of task-related variations in MN recruitment patterns, and it is pointed out that such variations may be related to the intraspinal topography of the respective MNs. It is suggested that these task related variations in MN recruitment behaviour might largely reflect topographic (and other) differences in the organization of spinal interneuronal systems responsible for the execution of different motor programs. PMID- 1610266 TI - [Case report of pathologic and criminal self injury]. AB - A case of morbid self-violence (Munchhausen Syndrome) leading to death and a case of criminal self-violence (cutaneous emphysema) are reported. The issue of such cases is discussed with regard to the consequences concerning judicial procedure of punishment and insurance. PMID- 1610267 TI - [The "inner gunshot residue"--a gunshot entry marker in gunshot of ridged skin]. AB - Gunshot residue below the surface of the skin is typical of a contact gunshot wound. However, in a case of our own, when a taxi-robber was shot by the cab driver through his right hand at a distance of several yards, this finding provoked quite a confusion. Only when experimental shots at thick glabrous skin were performed, it could be established that long range shots led to intraepidermal gunshot deposit too. The explanation of this phenomenon lies in the tenacity of thick skin. Unlike the thin hairy skin, which is punched out by the penetrating projectile, the thicker and more tenacious plantar/palmar epidermis gets displaced radially, the stratum germinativum tears and the projectile casts its gunshot residue in the pouch formed in such a manner. Therefore, intraepidermal gunshot residue is proof of an entrance gunshot wound but not always a sign of contact shot if the wound is located in the palmar or plantar region. It is typically produced by shots at thick skin. PMID- 1610268 TI - [Turner's syndrome: a revolution]. PMID- 1610269 TI - [Thought of the management of chronic diseases in children. The example of diabetes mellitus]. PMID- 1610270 TI - [Intensifying iron chelating therapy with desferrioxamine using implantable venous access catheters (Port-A-Cath)]. AB - Deferoxamine is still today the only preventive and curative treatment of transfusional hemochromatosis. It must be perfused daily, intravenously or subcutaneously, during several hours. Implantable infusion devices (Port-A-Cath) offer intravenous access, allowing to use higher doses, while avoiding local swelling due to subcutaneous injections. This device was inserted in 7 major thalassemic patients who presented with severe complications of iron overload, including 4 of them with signs of cardiac failure. Ferritinemias of all patients were lowered after intensifying iron chelation: cardiac function improved drastically in 2 patients. Devices were responsible for some complications: occlusion in one patient, local infections in two. This way of administration of desferal seems useful in patients with high ferritinemia and/or organic complications related to hemochromatosis. PMID- 1610271 TI - [Meconium aspiration syndrome in the region of Nord-Pas-de-Calais. Development of a training program for neonatal resuscitation]. AB - In the French region Nord-Pas-de-Calais a Public Health action was undertaken in order to set up a training program for neonatal resuscitation for the maternity hospitals personnel. The incidence and severity of meconium aspiration among the population of children admitted to the neonatal intensive care unit of Lille University Hospital during two 15 month-periods of time, before and after the training, were compared. The number of neonates who presented with meconium aspiration decreased from 54 during the first period to 9 during the second, i.e. from 7.2 to 1.3% with respect to the total number of hospitalized patients (p less than 0.001). On the contrary, the number of deaths did not decrease significantly. This regression of the meconium aspiration gives evidence for an improved quality of care at birth. Even if training is not the only factor, this evolution gives argument in favour of the efficacy of such actions. PMID- 1610272 TI - [Periungual capillaroscopy patterns in normal children]. AB - In children as well as in adults, capillaroscopy is an unsophisticated and non invasive technique which allows to investigate vascular acrosyndromes and systemic diseases. We have studied nailfold capillaroscopy patterns in 80 children without over vascular or systemic disease: pericapillary halos and haemorrhages increased with age and capillaries matured towards the typical hair pin structure seen in adults. The number of minor dystrophies increased with age and the venous subpapillary plexuses became less easily visible. PMID- 1610273 TI - [Critical study of diabetic ketoacidosis in children. Initial description and course during the first 24 hours of treatment]. AB - A critical analysis of the evolution during the first 24 hours was undertaken in 41 children and adolescents (age: 10.1 +/- 4.6 years) treated for diabetic ketoacidosis. Three of 4 children presented with ketoacidosis revealing diabetes. One of 4 was less than 6 years of age. Severe ketoacidosis (pH less than 7.15) concerned one third of children and were more frequent in the group of adolescents with already known diabetes. In these patients, ketoacidotic decompensation was attributed to psychosocial factors in most cases. Evolution was favorable in all cases, without complication. Blood glucose levels decreased from 28.7 mmol/l on arrival to 16.2 mmol/l after 2 hours of treatment and became stable at 10 mmol/l from the 12th to the 24th hours. The corrected blood sodium levels were stable, showing the adequacy of infusion solute osmolarities. Blood potassium was maintained at a normal level owing to early potassium supplementation. Ketoacidosis was corrected after about 12 hours, without bicarbonate administration when pH was greater than 7.15. Average perfused volumes were 3 l/m2/24 hours. Insulin doses were 2 UI/kg/24 hours and were inversely correlated with the admission pH (r = -0.6; p = 0.0001). This study shows the efficacy of a treatment taking into account the pathophysiology of diabetic ketoacidosis and the knowledge of the complication risk factors, by foreseeing the adjustments to be done with respect to individual and/or at risk situations. These precise descriptive data, collected on a large group of patients, establish a reference basis to follow evolution in the course of the treatment of diabetic ketoacidosis in children. PMID- 1610274 TI - [Incidence of autopsies in France. Consequence on the estimation of sudden death rate according to regions. Results from an epidemiologic survey on postneonatal mortality]. AB - In order to assess the actual rate of sudden infant death in France, an epidemiological survey was carried out. All the deaths of the postneonatal period were investigated from September 1986 to December 1987. The parents of the babies and the certifying physicians were involved in the survey, the results of the post mortem investigations were recorded. That material showed a low rate of necropsies among the sudden infant deaths (31% at the national level) and wide variations in the rates between the French regions (from 55 to 7%). Nevertheless the results of the autopsies as well as the clinical aspects allowed to calculate the unexplained sudden infant death rates by region according to the Beckwith's definition. These rates are ranging from 0.8 to 1.9 per thousand live births (mean 1.3). PMID- 1610275 TI - [Neonatal malignant tumors. Apropos of 75 cases]. AB - From 1975 to 1986, 75 neonates were treated at the Institute Gustave-Roussy for a malignant solid tumor, comprising 1.7% of the overall oncopediatric population treated during the same period of time. Of these 75 patients, 47 (62%) presented with neuroblastomas, 15 (20%) with mesenchymal tumors, 9 (12%) with germ cell tumors and 4 with various other types of tumors. Treatment consisted of surgery in 63 patients, chemotherapy in 43 and radiotherapy in 18. The 5 year crude survival rate was 77%. Neuroblastomas did the best with a crude survival rate of 89%. The young age of the patients resulted in two types of problems: immediate tolerance and long term sequelae. The therapeutic regimen should take into account the good prognosis of the majority of these tumors in order to decrease delayed effects. PMID- 1610276 TI - [Galactosialidosis with Kayser-Fleischer's ring]. AB - The case of a 4 year-old boy presenting with dysmorphic facies, hepatomegaly, splenomegaly, growth and psychomotor retardation is reported. Radiological pattern suggested a storage disease. Bone marrow differential cell count showed numerous storage cells with vacuolated lymphocytes. Enzymatic studies showed decreased beta-galactosidase and neuraminidase levels, leading to the diagnosis of galactosialidosis. This is the first Tunisian case reported, which differs from the other cases published by the presence of a Kayser-Fleischer ring. PMID- 1610277 TI - [Whooping cough with Bordetella parapertussis isolation in an HIV positive child]. AB - The authors report a case of whooping cough revealed by a pneumothorax in a 4 year-old boy with human immunodeficiency virus infection. Systemic signs of whooping cough were present. Bordetella parapertussis was isolated. Worsening of the HIV infection occurred simultaneously. PMID- 1610278 TI - [A rare cause of neonatal exudative enteropathy: congenital Langerhans cell histiocytosis (histiocytosis X)]. AB - A case of Langerhans cell histiocytosis is reported in a neonate. Intestinal involvement was especially diffuse and severe, presenting as a protein-losing enteropathy secondary to massive mucosal infiltration by histiocytic cells. The infant died at the age of 3 1/2 months despite therapy with corticosteroids and vinblastine then etoposide and interferon. Such an outcome confirmed the severity of forms with neonatal onset and digestive involvement. PMID- 1610279 TI - [Iconographic rubric. Bilateral calcified subdural hematoma and excluded fourth ventricle]. PMID- 1610280 TI - [Ataxia telangiectasia]. PMID- 1610281 TI - [Early measles vaccination]. PMID- 1610282 TI - [Maternal fever. Relationship with maternal-fetal infection in full term newborn infants]. PMID- 1610283 TI - [Intravenous immunoglobulins and aseptic meningitis]. PMID- 1610284 TI - [Formulation of a prescription for enteral and parenteral nutrition of newborn infants]. PMID- 1610285 TI - Lesbianism in China. AB - Lesbianism in China has a long but usually hidden history. This paper examines the historical and literary sources of the past to illustrate the history of lesbianism and then turns to a survey of lesbianism in the China of today. As in the past, lesbianism remains more or less hidden, and comes to light only occasionally. Data for contemporary China comes from a visit to an institution for delinquent young women, recent police records, and contemporary fiction. It has only been in the past 4 or 5 years that it was possible to talk about lesbianism and most lesbians are fearful of becoming identified. PMID- 1610286 TI - Premarital sexual behavior among Chinese college students in the United States. AB - Little is known about sexuality among Chinese in the U.S. There are reasons to believe that their sexual attitudes and behaviors would differ from those of Chinese in Asia as well as other groups in the U.S. This survey of ethnic Chinese college students in the U.S. examined the permissiveness of their attitudes toward premarital sex and their premarital sexual behavior with an eye toward their levels of acculturation. Over 60% approved of premarital sexual intercourse when the partners were in love or engaged. There was no significant gender difference in sexual permissiveness. Most of the men and women had engaged in kissing, necking, and petting, but most had not engaged in sexual intercourse. Gender differences were found in sexual experience: Chinese men were less experienced than Chinese women. Sexual permissiveness and experience were related to level of acculturation. Those who dated only Caucasians were more sexually experienced than those who dated only Chinese. Results are discussed in terms of differences in sexual attitudes and behaviors between Caucasian Americans and Chinese Americans and in terms of acculturation. PMID- 1610287 TI - Secular trends and sociodemographic regularities of coital debut age in Norway. AB - Gender and birth cohort differences and the influence of social background variables on the coital debut age were investigated in the general population of Norway. The data derive from a 1987 questionnaire on sexual behavior mailed to a random sample of 10,000 Norwegians of both sexes, ages 18 through 60; 63% responded to the questionnaire. 94.5% reported that they had experienced intercourse. The median coital debut age was 18.2 years. There were both cohort and gender differences. Younger cohorts have lower coital debut ages, and women younger than 35 years experienced their first intercourse at an earlier age than men in the same age group. When each independent variable was analyzed separately, there were substantial differences between educational levels and social classes with respect to age of coital debut. Multivariate analysis of six separate cohorts revealed independent effects of gender in the two youngest cohorts, whereas educational level had significant independent effects in all but the oldest cohort. Social class did not reveal any independent effect on coital debut age. Population density of the place of residence of the respondents was not substantially related to age of coital debut. Seen together, the independent variables explain about 13% of the variance in coital debut age (by multiple regression). PMID- 1610288 TI - Casual sex among Norwegian adolescents. AB - The issue of casual sex and amount of sexual experience was studied using data from a representative sample of 2997 Norwegians, 17-19 years old. Data were collected by anonymous self-administered questionnaires, and the response rate was 62.8%. Results showed that among adolescents, experience of casual sex to a large extent was a function of the time the individual had been coitally active. The amount of sexual experience was poorly related to social background and strongly related to life-style factors such as smoking and drinking of alcohol. A small minority of adolescents was found to have a sexual behavior deviating from that of the majority, and thus containing elements of potentially high risk for contracting HIV or other STDs. This minority of adolescents had the identifying characteristic of low self-reported intimacy with their first coital partner. PMID- 1610289 TI - Sexual activities and preferences in a United Kingdom sample of 16 to 20-year olds. AB - Data are reported on the sexual behavior of a random sample of 2171 youth, 16-20 years old, in two locations in the U.K. Lower bound prevalence estimates for a range of specific sex acts are presented with discussion of the likely biases in the data. Given concerns about the spread of HIV through the heterosexual population, emphasis is given to the nontrivial estimates of a number of potential transmission risk behaviors, in particular, heterosexual anal penetration. Data are also presented suggesting that experience with particular sexual acts is associated with maintenance of a desire to do these acts in the future. The implications of these findings for health education policy are discussed. PMID- 1610290 TI - Sexual behavior and attitudes of university students in Northern Ireland. AB - Two surveys of a Northern Ireland student sample were conducted in 1987 and 1988. A total of 419 female and 201 male subjects completed self-administered anonymous questionnaires concerning their behavior, knowledge, and attitudes towards sex, AIDS, homosexuality, contraception, and relationships. Results indicated a relatively low level of sexual experience, and for those with experience, relatively few partners. The possible influences of gender and religiosity on sexual behavior and attitudes, in the context of Northern Ireland, are discussed. Subjects reported considerable variation in the amount of sex education, but the majority received little or none. This student sample held relatively conservative attitudes towards love, sex, and marriage and this was particularly true for females and for regular churchgoers. In addition, attitudes towards homosexuality were negative (particularly among regular churchgoers). Attitudes towards contraception were more positive than expected among Catholic subjects, and few indicated that they would refuse to use contraceptives on principle. Responses to items about AIDS were highly uniform, suggesting that much of the information made available to the public has been absorbed. However, the lack of uniformity of response to more general items about sex, relationships, and contraception may indicate that fundamental changes in sexual behavior are unlikely to be brought about by influencing a rather narrowly defined set of attitudes about AIDS. PMID- 1610292 TI - Pharmacokinetic interaction between 1,3-butadiene and styrene in Sprague-Dawley rats. AB - Gas uptake studies were carried out to evaluate kinetic interactions between 1,3 butadiene and styrene in Sprague-Dawley rats. The animals were co-exposed by inhalation to a mixture of 1,3-butadiene between 20 and 6000 ppm (v/v) and styrene between 0 and 500 ppm. The data demonstrate that metabolism of 1,3 butadiene was partially inhibited by styrene. The inhibition was competitive at atmospheric concentrations of styrene up to 90 ppm. Higher concentrations of styrene resulted in a small additional inhibition only. The apparent Michaelis Menten constant for 1,3-butadiene, related to the average concentration in the organism of the animals, was Kmapp = 1.17 +/- 0.37 (mumol/l of tissue) and the corresponding atmospheric concentration at steady state was 560 ppm. The inhibition constant of styrene was found to be Ki = 0.23 +/- 0.30 (mumol/l of tissue). The maximal metabolic rate for 1,3-butadiene was 230 +/- 10 (mu/kg/h). PMID- 1610291 TI - S-phenylcysteine formation in hemoglobin as a biological exposure index to benzene. AB - Benzene is metabolized to intermediates that bind to hemoglobin, forming adducts. These hemoglobin adducts may be usable as biomarkers of exposure. In this paper, we describe the development of a gas chromatography/mass spectroscopy assay for quantitating the binding of the benzene metabolite, benzene oxide, to cysteine groups in hemoglobin. We used this assay to study the hemoglobin adduct, S phenylcysteine (SPC), in the blood of rats and mice exposed to benzene either by inhalation or by gavage. We were able to detect SPC in the hemoglobin of exposed rats and mice, to show the linearity of the exposure dose-response relationship, and to establish the sensitivity limits of this assay. For the same exposure regime, rats showed considerably higher levels of SPC than did mice. As yet, we have not been able to detect SPC in the globin of humans occupationally exposed to benzene. We attempted to determine whether the SPC found in hemoglobin originated from the metabolism of benzene within or outside of the red blood cell. We hypothesized that the greatest red blood cell metabolism would be associated with peripheral reticulocytes, which retain high metabolic capacity. After exposing rats to benzene, we isolated the red blood cells and used discontinuous Percoll gradients to fractionate them into age groups. No differences in SPC levels were found among any of the fractions, suggesting that the SPC found in globin originates from the metabolism of benzene to benzene oxide in a location external to the red blood cell. To our knowledge, this is the first demonstration of the nonenzymatic binding of the benzene metabolite, benzene oxide, to protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610293 TI - Decrease in bone strength of cadmium-treated young and old rats. AB - A decrease in mechanical strength of bones was observed both in young and old rats for long periods of administration of cadmium. Young (3-week-old) female rats were given 0 (control), 5 and 10 ppm cadmium in drinking water, respectively, for 20 weeks. Old (18-month-old) female rats were given 0 (control) and 40 ppm cadmium in drinking water, respectively, for 7 months. The compression strengths of bones of young rats which were given 10 ppm cadmium, and those of old rats which were given 40 ppm cadmium, significantly decreased at the distal end portion of femur. Cadmium contents in bones in the 10 ppm and 40 ppm groups were about 110 and 210 ng/g dry weight, respectively. The present result confirmed that cadmium has a lesional effect on the mechanical strength of bone at the concentration of 100-200 ng/g in dry weight of bone, for both young and old rats. PMID- 1610294 TI - Peroxisome proliferation due to di (2-ethylhexyl) adipate, 2-ethylhexanol and 2 ethylhexanoic acid. AB - The dose-response relationships for peroxisome proliferation due to Di (2 ethylhexyl) adipate (DEHA), 2-ethylhexanol (EH), 2-ethylhexanoic acid (EHA) have been investigated in rats and mice. Linear dose-response relationships were observed for induction of cyanide-insensitive palmitoyl CoA oxidation (PCO), used as a enzyme marker of peroxisome proliferation, by DEHA, EH and EHA in both species. Relative liver weights were also increased in a dose related manner. On a molar basis, DEHA was twice as potent as EH or EHA which were equipotent and PCO was stimulated to a greater extent in male mice than in rats or female mice. At doses above 8 mmol/kg/day, EH was toxic to rats (both sexes) and similarly EHA at 13.5 mmol/kg/day lead to the death of female rats. In a attempt to explain the species difference in carcinogenicity of DEHA previously reported, we also used Fischer 344 rats and B6C3F1 mice. DEHA administration (2.5 g/kg/day) to Fischer 344 rats and B6C3F1 mice lead to toxicity in female rats. Relative liver weights were increased in a dose related fashion by DEHA administration to both rats and mice, PCO but not catalase was markedly increased (up to 15 fold in male rats). Light microscopy examination indicated some glycogen loss, a dose related hypertrophy and increased eosinophilia in both rats and mice. Electron microscopy confirmed peroxisome proliferation accompanied by a marked reduction of lipid in the centrilobular hepatocytes. These data suggest EHA to be the proximate peroxisome proliferator derived from DEHA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610295 TI - Differences in the response of Sprague-Dawley and Lewis rats to bezafibrate: the hypolipidemic effect and the induction of peroxisomal enzymes. AB - The effects of bezafibrate administered at 10 and 50 mg/kg/day for 7 days to male Sprague-Dawley (SD) and Lewis rats were investigated in order to determine the interrelation between the changes in serum and hepatic lipid contents and activities of selected peroxisomal, microsomal and mitochondrial enzymes in the two rat strains. In both strains, bezafibrate effectively reduced serum and hepatic lipids, increased the liver weight, induced a proliferation of peroxisomes, and selectively elevated the activities of carnitine acetyltransferase and of the enzymes of the peroxisomal beta-oxidation system. Moreover, immunoblotting revealed that the drug specifically enhanced the concentration of only those peroxisomal enzymes involved in fatty acid beta oxidation. The data obtained demonstrate that although the responses initiated by bezafibrate are qualitatively similar in both strains, they differ in their magnitude in a dose-dependent manner, with the Lewis strain exhibiting a more pronounced response than the SD rats. These results show that dose-dependent strain differences as well as the generally known species differences should be taken into account in pharmacological and toxicological evaluations of fibrates in rodents. Furthermore, generalization and extrapolation from rodent studies should be treated with great caution. PMID- 1610296 TI - Changes in auditory brainstem response in rats chronically exposed to carbon disulfide. AB - The chronic effect of carbon disulfide (CS2) on the central nervous system (CNS) was studied by examining auditory brainstem responses (ABRs) in female rats (Jcl Wistar) exposed to 200 ppm or 800 ppm CS2 by inhalation, 6 h a day, 5 days a week, for 15 weeks. Two modes of ABRs evoked by clicks at 61 and 96 dB sound pressure levels (61 dB-ABR and 96 dB-ABR) were recorded during the exposure and for 6 weeks afterwards. Three main components (I, III and V) of ABRs were analyzed from the latencies and differences between latencies of them (interpeak latencies, IPL I-III, IPL III-V and IPL I-V). The latencies of the three components and IPLs of 96 dB-ABR in rats group exposed to 800 ppm of CS2 were significantly delayed during the exposure period. The delay of latency of component V and IPL III-V and I-V tended to increase with exposure time. At 61 dB ABR, the changes in the latency of component V, IPL III-V and I-V resembled those at 96 dB-ABR. For the rats group exposed to 200 ppm CS2, the latency of component I, IPL III-V and I-V at 96 dB-ABR were delayed significantly but transiently during the exposure period. For both groups, recovery from the latencies of the three components and IPLs of ABR was observed by the end of the recovery period. The delayed latencies of ABR observed in rats exposed to 800 ppm CS2 suggested a conduction dysfunction in the brainstem due to CS2 exposure.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610297 TI - Possible pitfalls in rat extended dermal toxicity testing: an hepatic-ocular syndrome. AB - During a sub-chronic dermal toxicity study, hepatic and ocular toxicity were detected unrelated to the compound being tested. The changes in the liver were characterized by hepatic centrilobular degeneration and fibrosis due to chronic passive congestion. Clinical chemistry results confirmed the active hepatic damage and cholestasis. The ocular changes were limited to the retina where diffuse retinal atrophy was seen originating adjacent to the optic nerve and progressing centrifugally. It is suggested that as a consequence of the bandaging technique, a state of passive congestion and cholestasis resulted. The decrease in flow of bile acids to the intestine caused disturbances in vitamin E absorption. The deficiency of the antioxidant vitamin was responsible for the retinal changes seen. PMID- 1610298 TI - Protection effects of procaine on oxidative stress and toxicities of renal cortical slices from rats caused by cisplatin in vitro. AB - Incubation of rat renal cortical slices with 2 mM cisplatin (CDDP) at 37 degrees C for different periods of time (15-180 min) increased malondialdehyde (MDA) formation, decreased intracellular glutathione (GSH), and inhibited gluconeogenesis in the slices. CDDP-induced MDA formation increased by 53% after 180 min of incubation and GSH decreased by 35% after 60 min of incubation. Both depletion of GSH and inhibition of gluconeogenesis preceded MDA formation. Procaine (2 mM) completely inhibited CDDP-induced lipid peroxidation without affecting depletion of GSH, but even potentiated gluconeogenesis inhibition, while 2 mM dithiothreitol (DTT) largely reversed all of these biochemical indices. After 240 min of incubation, 2 mM CDDP produced marked cytotoxicities, characterized by an increase in leakage of alkaline phosphatase (ALP) (132%), lactate dehydrogenase (LDH) (115%) and N-acetyl-beta-glucosaminidase (NAG) (157%), decrease in intracellular K+ (64%), and change in total water contents in the slices. Procaine (2 mM) showed protection against CDDP-induced cytotoxicities to a certain extent. These results suggest that depletion of GSH might be a determinant step in the oxidative stress and subsequent cytotoxicity, and that procaine is a powerful antioxidant and would be a promising drug for ameliorating some of the adverse effects of CDDP. PMID- 1610299 TI - Activity of glutathione-S-transferase in rat liver and kidneys after administration of lead or cadmium. AB - The influence of an acute dose of lead nitrate or cadmium chloride on the activity of glutathione-S-transferase (GST) was investigated in rats. CdCl2 (10 mumol/kg) did not influence the enzyme activity in either organ. In contrast Pb(NO3)2 (100 mumol/kg) caused a significant increase of GST activity in both organs. SDS polyacrylamide gel electrophoresis (SDS-PAGE) showed that in liver the activity enhancement is due mainly to the induction of the isoenzyme GST 7-7, while in the kidneys the activity of all the isoenzymes is increased. PMID- 1610300 TI - Structure-toxicity relationship of ethylene glycol ethers. AB - The ultimate purpose of the present study was to evaluate correlations between acute in vivo and in vitro toxicity and log P (P is n-octanol-water partition coefficient). The in vitro toxicity to cloned cells (neuroblastoma N18TG-2 and glioma C6) in culture (ED50) and the in vivo toxicity to mice (LD50) of ethylene glycol ethers were studied in terms of the structure-activity relationship. The test ethers showed a wide range of ED50 values in both cells. LD50 was determined under two conditions: LD50-cont. was estimated in mice pretreated with olive oil and LD50-CCl4 in CCl4-pretreated mice. Multiple regression analyses revealed a significant correlation between log 1/LD50 and log P as follows: log (1/LD50 cont.) = -0.120 (log P)2+0.487log P-1.182, and log (1/LD50-CCl4) = -0.128 (log P)2+0.566log P-1.157. There was no significant correlation either between ED50 and LD50 or between ED50 for N18TG-2 and ED50 for C6. The results suggest that metabolic activation might not occur during acute toxicity from the ethers, and that hydrophobicity, expressed as log P, plays an important role in acute toxicity. PMID- 1610301 TI - Glycosaminoglycan patterns in gingival proteoglycans of rat with age. AB - Among the potential biochemical indices that are closely associated with craniofacial development are the proteoglycans. Gingival segments from the palate of 4-, 6-, 8-, 12- and 18-week-old rats were incubated for 4 h in medium containing [3H]-glucosamine and [35S]-Na2SO4, and subjected to proteoglycan isolation and glycosaminoglycan analysis. Two distinct proteoglycan fractions differing in the degree of sulphation were obtained by ion-exchange chromatography. The incorporation of both labels in the undersulphated fraction increased with age; there was a pronounced decrease with age in the sulphated proteoglycan fraction. The undersulphated proteoglycans showed an age-dependent decrease in hyaluronic acid, and increase in dermatan sulphate and chondroitin 4- and 6-sulphates. Gel filtration of the sulphated proteoglycan fraction yielded high and low molecular-weight proteoglycans, the glycosaminoglycans of which were particularly rich (61-76%) in dermatan sulphate. Smaller quantities of chondroitin 4- and 6-sulphates, and heparan sulphate were also present. All glycosaminoglycans showed a decrease in content with age. The findings suggest a possible correlation between gingival proteoglycan/glycosaminoglycan patterns and development. PMID- 1610302 TI - A scanning electron microscopic study of rete ridges in the cheek pouch of normal young, adult and aged Syrian hamsters. AB - Cheek pouches were removed from BIO 87.20 male hamsters 4 weeks, 8 months or 18 months of age. One pouch from each animal was routinely processed for light microscopy. The epithelium and connective tissue of the remaining pouches were separated with EDTA and routinely processed for scanning electron microscopy. Two types of rete ridge were found: simple, consisting of a single epithelial ridge or blunt projection and complex, made up of multiple interconnecting ridges. The simple type predominated at 4 weeks (90%) but the complex type predominated at 8 (58%) and 18 months (73%). Although the 8- and 18-month pouches were significantly larger than the 4-week ones, the total number of rete ridges was similar at all ages. This, taken in association with the shift in type with age, suggests that the simple rete ridges develop into the complex ones. With increasing age more of the complex rete ridges took on the characteristics of touch domes. These changes in the shape of the rete ridges with age need to be taken into account in studies on experimentally altered cheek pouches so that they are not mistaken as pathological changes. PMID- 1610303 TI - Glycosidase activities in gingival crevicular fluid in subjects with adult periodontitis or gingivitis. AB - Specific glycosidase activities were determined in samples of gingival crevicular fluid (GCF) collected from eight predetermined sites in two groups, each of 20 adult patients, with either gingivitis or periodontitis. The total activities (as units of enzyme activity per sample) of alpha-L-fucosidase, sialidase, beta-N acetylglucosaminidase, beta-galactosidase, beta-glucosidase and alpha-glucosidase were significantly greater in the periodontitis group. In contrast, the total beta-mannosidase and hexosaminidase A activities were significantly greater in the gingivitis group, while there was no significant difference in the total alpha-mannosidase activity between the groups. Only the specific activities (as units of enzyme activity per min per microliter of GCF) of beta-mannosidase and hexosaminidase A were significantly different between the groups being greater in the gingivitis group. When used to predict the clinical status of individual periodontal sites, the total enzyme activities had specificity and sensitivity values of 91.9 and 61.3%, respectively. Measurement of glycosidase activities might thus have a role in monitoring the efficacy of periodontal treatment or in predicting future periodontal disease but this will require further investigation. PMID- 1610304 TI - Levels of salivary cystatins in periodontally healthy and diseased older adults. AB - Cystatins are cysteine protease inhibitors present in a variety of tissues and body fluids, including saliva. One possible function of these molecules may be to modulate tissue destruction in periodontal diseases. To investigate the potential role of salivary cystatins in these events, the levels of cystatins in saliva from periodontally healthy and diseased individuals were measured by enzyme linked immunosorbent assay. Flow rates and total protein content were determined in all the samples collected, while cysteine protease inhibitory activity was assessed in submandibular-sublingual secretions. Statistical analysis showed no significant differences in the levels and activity of salivary cystatins in periodontally healthy and diseased individuals. These findings suggest that comparing the levels of cystatins in glandular salivas may not be a suitable indicator of periodontal disease status. PMID- 1610305 TI - Differences in the transport systems between cementocytes and osteocytes in rats using microperoxidase as a tracer. AB - Microperoxidase (MP) tracer was injected intravenously into rats to investigate any differences in transport pathways of tissue fluids in the lacunae and canaliculi of cementum and bone. Light microscopically, in deep cementum lacunae, pericellular spaces contained a large amount of MP, while close to the cementum surface, the spaces contained scarcely any. In bone, MP was detected throughout all pericellular spaces. MP was detected intracellularly as granular reaction products in most cementocytes and osteocytes. Electron microscopically, MP was found in the pericellular spaces of cementum and bone lacunae, particularly on collagen fibrils and amorphous material. MP deposits were also intense along the plasma membrane of cementocytes in the deep cementum and along the innermost edge of the deep cementum matrix and bone matrix. In uptake of MP by cementocytes, although extracellular tracer was deposited extensively along the plasma membrane of the deeply positioned cementocytes, uptake by these deep cementocytes was less than that of those close to the surface. However, in bone, most osteocytes showed uniform uptake. These results suggest that the transport pathways for tissue fluids in cementum are in the pericellular spaces, but that cementum has an uneven circulation of tissue fluid. In cementum, although there seems to be a well-developed canalicular system to transport tissue fluid into the deep regions, the deep cementocytes had less endocytotic ability than those close to the surface. PMID- 1610306 TI - Systemic lead absorption in human tooth roots. AB - One-hundred and five impacted and erupted sound teeth were analysed for lead content by graphite furnace atomic absorption spectrophotometry. The results showed that lead accumulated before eruption, presumably soon after the onset of dentine formation. The accumulation in dentine was systemic, without any contribution from the oral environment. The amount of lead in dentine may denote the amount of absorption into the body and serve as a precise index to body burden as no absorption from the mouth can take place. In adults, impacted and erupted teeth can be used together in any research and the donor's age can be considered as the period of lead accumulation. PMID- 1610307 TI - Immunohistochemical investigation of epidermal growth factor receptor expression during periods of accelerated rat incisor eruption. AB - The effect of accelerated odontogenesis of the rat mandibular incisor on the expression of receptors for epidermal growth factor (EGF) was examined using specific monoclonal antibodies to the receptor molecule. Acceleration of odontogenesis was achieved by regular trimming of the tooth crown. At normal eruption rates the major area of cross-reactivity was over the secretory ameloblasts. Some labelling of the papilla and preameloblasts was evident. When proliferation was increased the major area of effect was at the preodontoblast/odontoblast boundary where there was a marked increase in labelling, initially at the proximal end of the cell adjacent to the basal lamina. The ameloblasts did not show such a dramatic increase in receptor numbers. Increase in labelling was also evident in the remainder of the papilla. The results suggest that an increase in proliferation with normal morphogenesis is associated with an overall increase in the numbers of EGF receptors, particularly in a population of cells immediately before and after elongation and differentiation of odontoblasts. PMID- 1610308 TI - The effects of epidermal growth factor, transforming growth factors alpha and beta and platelet-derived growth factor on murine palatal shelves in organ culture. AB - Palatal shelves isolated from day-13 embryonic mice were explanted on to the surfaces of collagen gels either singly or in pairs with their medial edges in contact, and cultured submerged in a 1:1 mixture of Dulbecco's modified Eagle's medium/Ham's F12 medium. The medium was supplemented with either 10 ng/ml epidermal growth factor (EGF), 10 ng/ml transforming growth factor alpha (TGF alpha), 1 ng/ml transforming growth factor beta (TGF beta 1) or 2 ng/ml platelet derived growth factor (PDGF) all in the presence or absence of 2.5% donor calf serum (DCS). Cultures were terminated after 0, 24, 48 or 72 h and processed for histological and immunocytochemical examination. In serum-free medium and medium supplemented with 2.5% DCS the palatal epithelia differentiated in a manner similar to that seen in vivo (oral, keratinization; nasal, pseudostratified, ciliated columnar cells and medial edge, epithelial degeneration). A similar pattern was obtained in serum-free medium supplemented with either EGF or TGF alpha. However in cultures with either EGF or TGF alpha plus 2.5% DCS present in the medium, medial-edge epithelial degeneration was inhibited and the oral epithelia were more heavily keratinized. The mesenchyme of such cultures stained more intensely for various extracellular matrix molecules. In TGF beta 1 supplemented cultures (with, but especially without, serum supplementation) the epithelia were thin, medial-edge epithelial degeneration was marked, and the fibronectin content of the mesenchyme was increased. PDGF prevented medial-edge epithelial degeneration in the presence, but not in the absence, of serum; mesenchymal extracellular molecules were not as prevalent as with the EGF treatment. These results indicate that exogenous growth factors (including those present in serum) exert effects on organ-cultured mouse palatal shelves in a fashion similar to their effects in cell culture and that controlled physiological levels of such factors may be important in mouse palatal development. PMID- 1610309 TI - Some notes on the diffusion of acidic and alkaline agents into natural human caries lesions in vitro. AB - The aim was to obtain information on the penetration of ions, in particular H+ and OH-, into a wide variety of natural caries lesions in human teeth. Thirty seven permanent teeth were slit in half and soaked in a 1% neutral (blue) litmus solution for at least a week. The cut face of the tooth was painted with a transparent, colourless nail varnish before the tooth was immersed in either of 0.1 M hydrochloric acid or 0.1 M phosphoric acid. In a reverse experiment the samples were soaked in acid (red) litmus solution and then immersed in 0.1 M sodium hydroxide after varnishing the cut face. All solutions were saturated with enamel apatite to avoid the possibility that the solutions might etch their way into the enamel. The colour change was recorded photographically. Several days of external acid/alkali exposure were required to change the litmus colour in the body of most of the lesions, suggesting that diffusion of acidic and alkaline species through the natural surface into the body was slow. The presence of a well-mineralized surface layer covering the lesion postponed the colour change. In contrast, the colour change of two root surface lesions was rapid, occurring within an hour. Thus, because the lesion body is relatively isolated and because lesion fluid is in intimate contact with the enamel apatite, we conclude that lesion fluid is close to saturation with respect to this mineral. Further, a pH change of lesion fluid in vivo paralleling that in plaque after a sucrose intake is unlikely.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610310 TI - Development of an orofacial model of acute inflammation in the rat. AB - An appropriate model was created by the paraperiosteal injection of mustard oil (20% allyl isothiocyanate dissolved in mineral oil) into the periarticular temporomandibular tissue of anaesthetized rats. Inflammation was assessed by the plasma extravasation of Evans' blue dye bound to plasma protein. This was confirmed visually and compared spectrophotometrically with the contralateral untreated control site (p less than 0.0005). A time-course study of the effect of mustard oil on Evans' blue extravasation revealed a gradually increasing effect that was maximal at 30 min after administration, with no further increase at 60 min. A dose-response study showed that giving 30 microliters of 20% mustard oil produced the maximal effect, with no further increase from 50 microliters. To confirm induction of inflammation, polymorphonuclear neutrophil infiltration was assessed morphometrically and found to increase in the treated tissue compared with the contralateral untreated control (p less than 0.001). PMID- 1610311 TI - Absence of association between a preferred chewing side and its area of functional occlusal contact in the human dentition. AB - Preference for a particular chewing side may be influenced by several factors, one of which could be the functional contact area on each side of the dentition. In this study, interocclusal wax records were made for each of the 30 subjects. A digital image of the transilluminated wax record was analysed to group 'grey' values into categories of wax thickness. The total area for tight and intermediate tooth contacts was calculated for both the left- and right-hand sides of each subject. The chewing-side preference was recorded. No correlation was found between the area of occlusal contact on one side and the preference for chewing on that side. Occlusal contact area does not appear to be a determinant of chewing-side preference. PMID- 1610312 TI - Alpha-amylase circadian rhythm of young rat parotid gland: an endogenous rhythm with maternal coordination. AB - The circadian rhythm of alpha-amylase, E.C. 3.2.1.1. alpha-1,4-glucan-4 glucanohydrolase) in the parotid glands of 25-day-old rats were studied under different experimental designs (fasting, reversed photoperiod, constant lighting conditions and treatment with reserpine and alpha-methyl-p-tyrosine). The rhythm of fasted rats did not change. There were modifications in the rhythm of rats submitted to a reversed photoperiod or treated with reserpine or alpha-methyl-p tyrosine. The rhythm was present, with changes in the acrophase, in parotids of rats kept during their gestation and postnatal life in constant light or dark. Results suggest that the circadian rhythm of alpha-amylase in parotid gland of young rats is endogenous, synchronized by the photoperiod, and with maternal coordination. PMID- 1610313 TI - Technical possibilities in the school situation for the education of hearing impaired children. AB - For hearing-impaired children, the main problem in the classroom is the signal-to noise ratio. To improve the signal-to-noise ratio, several class systems have been developed, three of which have been investigated in this study. The systems are shown to be equivalent in a situation without a channel for pupil response. Application of such pupil response channels will decrease the improvement in signal-to-noise ratio brought about by the class system. It is argued that the choice among several combinations of class system and pupil response channel is governed by the primary goal of education and how this goal is to be achieved. PMID- 1610314 TI - Frequency-specific auditory brainstem responses to bone-conducted stimuli. AB - The feasibility of recording bone-conducted auditory brainstem responses (ABRs) to 500-Hz and 2000-Hz tone bursts and clicks was investigated in normal-hearing adults. For all 3 stimuli, responses were detectable in all subjects at 30 dB nHL. At 20 dB nHL, the tone burst responses were detectable in 80-87% of the subjects, demonstrating that even the responses to 500-Hz tone bursts were relatively robust. Latencies and amplitudes of the responses were related to the stimuli. The cochlear locations contributing to the responses were investigated using high-pass masking. Derived-band analysis indicated reasonably good frequency specificity for the tone burst responses and a broad representation for the bone-conducted click, despite its lower frequency spectrum. The results of this study support the use of bone-conducted tone burst ABR for demonstrating frequency-specific normal cochlear sensitivity. PMID- 1610315 TI - Dependence of auditory brainstem response on click polarity and high-frequency sensorineural hearing loss. AB - An investigation is presented on the effect of click polarity upon the auditory brainstem response (ABR) in cases of simulated high-frequency hearing loss. A high-frequency hearing loss was stimulated in 12 normal subjects by applying a high-pass noise masker, the noise cutoff frequency being varied in half-octave steps through the range of audiometric frequencies. With this paradigm, the effects of click polarity on the ABR are similar to those reported in patients with high-frequency hearing loss, including changes in waveform morphology and substantial peak latency shifts. To evaluate the role of individual cochlear frequency channels in a more direct way, half-octave narrow-band responses were determined by pair-wise subtraction of the high-pass-noise-masked responses. As far as ABR peak latencies are concerned, stimulus polarity effects tend to increase towards the lower frequency bands. Thus, the selective elimination of the contribution to the ABR of cochlear high-frequency channels can be held responsible for the increased dependence of ABR on click polarity observed in high-frequency hearing loss. However, statistical evaluation of peak I, III and V latencies, both in high-pass-noise-masked and in narrow-band ABRs, reveals that the latency effects are not systematic between subjects. Mechanisms producing the observed rarefaction-condensation differences, possible explanations for the large intersubject variability and the consequences for clinical interpretation of ABR are discussed. PMID- 1610316 TI - Frequency response differences of four gain-equalized hearing aid prescription formulae. AB - The relative differences between the NAL, Berger, Lybarger und POGO hearing aid prescriptions were evaluated using 8 hypothetical audiograms and 81 actual hearing loss cases. The gains of the prescriptions were equalized, making the prescriptions maximally similar, as would presumably occur when the aids are worn. Statistically significant differences in the frequency responses of the prescriptions were found, with up to 17 dB gain difference observed; however, the gain differences at any given frequency were generally less than 8 dB. Sharply sloping hearing losses had the greatest differences between prescriptions. The NAL and Berger prescriptions were most disparate, while POGO and Lybarger were most similar. As large differences in prescribed gain are rare, research into the relevance of such small differences in frequency response is advocated as a precursor to study of the optimal prescription formula. PMID- 1610317 TI - Psychophysical studies using a multiple-electrode cochlear implant in patients who were deafened early in life. AB - Psychophysical studies were conducted on 10 cochlear implant patients, between 5 and 23 years of age at the time of surgery, who were deafened prior to 4 years of age. The multiple-electrode prosthesis manufactured by Cochlear Ltd. was used. Identification studies, the recognition of 2-4 stimuli after some training, were conducted on 3 of the 10 patients. For current level and repetition rate identification, performance was comparable to that observed for postlingual adult patients. For electrode position identification, however, performance was much poorer than that observed for postlingual adults. In general, the difference limens for current level, repetition rate and duration, and the gap detection thresholds were similar to those observed for postlingual adults. For 3 patients whose etiology was Usher's syndrome, the repetition rate limens at higher rates were larger than those of the other patients. The limens for electrode position, measured in a discrimination task, were 1-3 electrodes for most patients. However, for 3 patients, limens of 6-10 electrodes were recorded. For numerosity judgements, the counting of stimuli in a temporal series as a function of the rate of presentation, the patients were less successful at counting for rates of 3-8/s than for lower rates (1-2/s). PMID- 1610318 TI - Pseudomembranous colitis. PMID- 1610319 TI - Helicobacter pylori and peptic ulcer disease. PMID- 1610320 TI - Hepatic cavernous haemangioma: a 10 year review. AB - Between January 1981 and July 1991, 61 patients with hepatic haemangiomata were examined at Westmead Hospital. There were 14 males (22%) and 47 females (78%). The age range was 26-85 years with a median of 49 years. Forty-one had abdominal symptoms but these could be attributed to a haemangioma in only seven cases. There was at least one subcapsular lesion in 17 (28%). Six of the seven symptomatic lesions were subcapsular and five of these were giant haemangiomata (i.e. more than 4 cm in greatest diameter). One large symptomatic lesion was intrahepatic. No association was observed between hepatic haemangiomata and other hepatic or extrahepatic diseases. Haemangiomata were resected from six patients, four of whom were symptomatic. Symptoms improved in all four but did not resolve completely in any. Follow-up ranged from nil in five patients to 108 months in one. The median follow-up was 12 months after initial diagnosis. Ten patients showed evidence of change in their lesions or symptoms while under observation. Only three had worsening symptoms or suspected change in size of a haemangioma. This study highlights the benign, static nature of most hepatic haemangiomata. When this lesion is suspected, the diagnosis should be confirmed with ultrasound (US) and labelled red blood cell scanning (RBCS). Referral for evaluation by a specialist hepatobiliary surgery unit is necessary when symptoms are intolerable, increasing size is definitely demonstrated or the diagnosis is uncertain and cannot be established without specialized investigations. Bleeding into or from these lesions is rare. PMID- 1610321 TI - Operative cholangiography: a perspective. AB - Two hundred and eighty-seven patients having operative cholangiograms were identified from a prospective study of 346 patients undergoing surgery for gallstones. Forty-two patients (14.6%) had filling defects and bile duct (BD) exploration. The false-positive exploration rate was 2.8%. Eight patients (2.8%) had unexpected BD calculi with no abnormality in pre-operative liver function tests or ultrasound. If a policy of selective operative cholangiography is pursued, then failure to detect a small number of duct stones must be expected, although unnecessary duct exploration is likely to be eliminated. The clinical significance of undetected BD calculi remains debatable. PMID- 1610322 TI - Value of fine needle aspiration biopsy cytology in the diagnosis of discrete hepatic lesions suspicious for malignancy. AB - Ninety-five sequential computerized tomography (CT) guided fine needle aspirates (FNA) of the liver, taken between January 1986 and December 1989 were reviewed to assess the accuracy of this method in diagnosing discrete hepatic lesions suspicious for malignancy. Clinical follow-up information, or a tissue diagnosis or both were available in 71 of these cases. False-negative results were found in four of the cases. Forty-six cases in the group gave a positive result with FNA and confirmatory tissue diagnosis was made in 25 of these cases. Detailed clinical follow-up produced additional support for the diagnosis in 20 other cases. Twenty-four cases were negative but clinical follow-up indicated that there were four false-negative diagnoses. The one false-positive case in this series was diagnosed as a hepatocellular carcinoma in a patient with haemochromatosis. Overall, the results gave a sensitivity of 90% and a specificity of 87%. PMID- 1610323 TI - An evaluation of radionuclide bone scanning and liver ultrasonography for staging breast cancer. AB - The use of nuclear bone scanning and liver ultrasonography to stage breast cancer is an established practice in many hospitals. A 3 year prospective study was undertaken to assess the usefulness of these two investigations. Three hundred and fifty-eight patients were analysed: 133 had stage I disease, 188 were stage II and 37 were stage III. Bone scans were performed on 339 (94.7%) patients; 302 had stage I or stage II disease; and 37 were stage III. Bone scans were positive for metastases in only 0.9% of stage I and II patients but were positive in 16.2% of patients with stage III disease. None of the 309 (96.2%) stage I or stage II patients who had an ultrasound scan had any liver metastases detected whereas positive scans were obtained in 5.4% of stage III patients. It can be concluded that the incidence of demonstrable bone or liver metastases in stage I and stage II breast cancer patients is so low that the use of routine scanning can be abandoned. PMID- 1610324 TI - Intravenous or oral adjuvant CMF for node-positive breast cancer. AB - To assess the optimal duration and method of administration of adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy, 116 patients with positive axillary nodes after total mastectomy and axillary dissection were reviewed retrospectively. CMF was administered in three progressively shorter regimens, which consisted of oral CMF for either 12 or six cycles and intravenous (i.v.) CMF for six cycles. Median follow-up for surviving patients was 62 months. The three groups were matched for major prognostic factors. There was no advantage in using more than six cycles of adjuvant CMF. There was an improved crude 3 year disease-free survival (84 vs 65%, P = 0.05) and a trend towards improved overall survival (92 vs 85%, P = NS) in patients treated with six cycles of oral CMF compared with i.v. CMF. Survival rates were not significantly different beyond 3 years. Leucopenia and alopecia were more severe with oral CMF (P less than 0.01), and compliance worse with oral CMF x 12 (P = 0.01). Since the data suggest that i.v. CMF is at least as equal as oral CMF a randomized controlled trial should be undertaken. PMID- 1610325 TI - How accurate is a computerized surgical audit when resident medical staff collect the data? AB - Since July 1988 all eight general surgeons at Fremantle Hospital have used a computer-based surgical audit and discharge system. At the time of writing (September 1991) 10,919 computer-generated discharge letters have been produced by the system. This paper describes the system and reports a series of quality control assessments carried out between 1 July 1988 and 30 June 1990 during which 30 pre-registration surgical residents completed 5,716 data collection forms. It was found that: (1) data collection for 23 of 24 monthly surgical audits was at least 95% complete; (2) outstanding surgical discharge summaries were reduced by 89%; (3) the residents recorded 17/19 wound infections and identified 15 (79%) of these as a surgical complication; and (4) the residents tended to under-record complications in patients who had more than one complication during their hospital stay. It was concluded that the system was robust, and that resident staff collected data in such a way that good quality computer-generated discharge letters were produced in a timely manner. Closer attention to aspects of data collection will be required before the optimum surgical audits of the QX system can be generated. PMID- 1610326 TI - Bile acids do not modify the effects of pepsin on the fine structure of human oesophageal epithelium. AB - Oesophageal mucosal specimens (n = 250) were taken from 25 normal subjects (14 females, 11 males; median age 52 years; range 19-63 years) and incubated in physiological saline, pepsin and bile acid solutions to determine whether conjugated bile acids modify the epithelial cytotoxic action of pepsin. Short (5 min) and long (22 min) incubations were carried out and the results were assessed by transmission electron microscopy. Six different parameters of epithelial damage were scored (0-4) by a single 'blinded' pathologist for each of four epithelial layers. The scores after incubation in saline (pH 7 and titrated to pH 2 with HCl) were not different from those of the controls (P = 0.35). Both pepsin and bile acids (pH 2) caused more damage than saline at pH 2 (P less than 0.001) which was similar for the two substances (P = 0.136). Conjugated bile acids in combination with pepsin (pH 2) did not alter the overall extent or pattern of damage caused by pepsin alone (pH 2); P = 0.142). Conjugated bile acids, in concentrations commonly encountered during gastro-oesophageal reflux, did not appear to modify the cytopathic effects of pepsin on oesophageal mucosal cells in vitro. Conjugated bile acids may not be important in the pathogenesis of oesophagitis in patients with acid/peptic gastro-oesophageal reflux. PMID- 1610327 TI - Selective embolisation of intrahepatic aneurysms. AB - The radiological techniques that can be used to selectively embolise small arteries have improved markedly in the past few years. This article discusses the use of transcatheter embolisation in the management of three patients with aneurysms involving the intrahepatic arterial tree. PMID- 1610328 TI - Cardiac rupture from blunt trauma. PMID- 1610329 TI - Survival following non-penetrating trauma of the great cardiac vein. AB - A 62 year old female who survived cardiac tamponade due to an isolated tear to the great cardiac vein in a motor vehicle accident is presented. It is believed that this is the first report of such an isolated blunt cardiac injury. PMID- 1610330 TI - Unilateral hydronephrosis secondary to blunt ureteral trauma, presenting with hypertension and erythrocytosis. PMID- 1610331 TI - Congenital tracheo-oesophageal fistula in a young adult. AB - Congenital tracheo-oesophageal fistula (TEF) is rare in adults. Patients who present with repeated attacks of chest infection since birth or cough, choking and cyanosis during feeding should be investigated for TEF. It should be possible to detect all cases of tracheo-oesophageal fistulae using bronchoscopy, oesophagoscopy and CT either singly or in combination. These investigations also help in deciding on the route of exploration and the type of surgery. Disconnection of the abnormal fistulous tract brings dramatic relief of symptom and prevents further pulmonary damage. PMID- 1610332 TI - Corporate Angel Network: everybody wins! PMID- 1610333 TI - Analysis of accidents during instrument approaches. AB - General aviation and air taxi approach phase accidents, which occurred during Visual and Instrument Flight Rules (VFR and IFR, respectively) over the last 25 years, were analyzed. The data suggest that there is a 204% higher risk during the approach and landing phase of VFR flights, than during similar IFR operations (14.82 vs. 7.27 accidents/100,000 approaches). Alarmingly, the night single pilot IFR (SPIFR) accident rate is almost 8 times the rate of day IFR, 35.43 vs. 4.47 accidents/100,000 approaches, and two and a half times that of day VFR approaches, 35.43 vs. 14.82 accidents/100,000 approaches. Surprisingly, the overall SPIFR accident rates are not much higher than dual-pilot IFR (DPIFR), 7.27 vs. 6.48 accidents/100,000 approaches. The generally static ratio of the statistics for SPIFR/DPIFR accident rates may be accounted for by little or no change in general aviation cockpit technology during the last 25 years, and because IFR operational flight task management training has not kept pace. PMID- 1610334 TI - Through the canopy glass: a comparison of injuries in Naval Aviation ejections through the canopy and after canopy jettison, 1977 to 1990. AB - Two methods of ejection from tactical aircraft are commonly used: jettisoning the canopy prior to seat travel, and ejecting through a closed canopy. This report compares the ejection injury experience of Naval Aviation in each mode during January 1977-August 1990. During that period, 336 through-canopy and 580 canopy jettison ejections were accomplished. The former group sustained 10.7% fatal injuries, and only 17.0% egressed injury-free. By comparison, the latter cohort incurred only 4.7% fatalities and fully 31.9% egressed without injury. Analysis of patterns of injuries confirms higher G-forces in through-canopy ejections, resulting in not only more injuries, but more severe injuries. In spite of these findings, we discuss the compelling tactical and financial reasons to consider through-canopy systems. PMID- 1610335 TI - Limb blood flow while wearing aircrew chemical defense ensembles in the heat with and without auxiliary cooling. AB - The effect of auxiliary air cooling on endurance time and limb blood flow in the heat (37 degrees C, 50% r.h., target time = 150 min) while wearing aircrew chemical defense (CD) ensembles was examined. Eight males were dressed in aircrew CD ensembles with or without an air-cooled vest. After an initial 10 min treadmill walk and 20 min of seated rest, the subjects alternately rested and exercised on a cycle ergometer (10 min rest, 10 min exercise) resulting in an overall metabolic rate of 240 W. Arm and leg blood flow (ABF, LBF), determined by venous occlusion plethysmography, were significantly lower with air cooling (AC) than with no cooling (NC) during the same time period (p less than 0.05). Endurance time was much greater with AC than with NC (150 min AC vs. 92 +/- 0.08 min NC, p less than 0.01). Arm and calf skin temperatures, rectal temperature and heart rate were all significantly lower with AC than with NC (p less than 0.05) after the onset of the cycle exercise. The results show that the use of the air cooled vest under these conditions was able to increase heat tolerance and reduce blood flow to the periphery. PMID- 1610336 TI - Eyeglass use by U.S. Navy jet pilots: effects on night carrier landing performance. AB - The purpose of this study was to test the hypothesis that the night carrier landing performance of pilots who do not need prescriptive eyeglasses to fly is better than the performance of pilots who do. Night carrier landing scores (NCLS), age, career jet flight hours, and total career flight hours were obtained for 122 U.S. Navy fighter pilots participating in air combat maneuver training at NAS, Oceana, VA. of the pilots with NCLS, 16 used a prescribed spectacle correction while flying, 106 did not. This study compared the NCLS of the two groups of pilots, those with glasses and those without. We found no significant difference in NCLS between the two groups of pilots--even when the pilots were matched on the basis of age and flight experience. We conclude that pilots who have a refractive error and are required to wear an eyeglass correction while flying perform night carrier landings as well as the pilots who have no refractive error and are permitted to fly with no eye glass correction. PMID- 1610337 TI - The mortality of British Airways pilots, 1966-1989: a proportional mortality study. AB - Of 446 deaths among serving and retired British Airways pilots between 1966 and 1989, 411 were analysed using the Proportional Mortality Ratio (PMR) technique. After removal of the predictable excess of aircraft accidents, excesses of cancer (PMR 1.31) and other accidents (1.60) were balanced by deficits in diseases of the circulatory (0.83) and respiratory (0.49) systems. While lung cancer was close to expectation (1.10), consistent excesses were shown in all analyses for malignant melanoma (6.68), cirrhosis of the liver (2.88), colon cancer (2.30) and brain/CNS cancer (2.68). Consideration of these ratios in relation to pilots' lifestyle and occupation leads to the conclusion that the brain/CNS cancer excess must be studied further. PMID- 1610338 TI - Recovery of the hypoxic ventilatory drive of rats from the toxic effect of hyperbaric oxygen. AB - Hyperbaric oxygen (HBO) exposure reduces the hypoxic ventilatory drive (HVD), probably by damaging the carotid bodies. The recovery of the HVD from HBO exposure was studied. The HVD was calculated from whole body plethysmographic recordings of the ventilatory response to greater than 85% and 2% O2 in N2 mixtures. Five groups of rats were exposed to HBO for 9 h at pressures of 1.9, 2.0, 2.1, 2.2, and 2.4 ATA, respectively. Each rat underwent three control measurements on different days prior to HBO exposures and then at various intervals following the exposure. Postexposure HVD was reduced to 28% of control values in the high PO2s. Ninety percent recovery of pre-exposure HVD was evident by 12-48 h although in some animals exposed to relatively low PO2s (1.9 and 2.0 ATA) HVD stabilized at a level lower than 100%. The recovery of the HVD in percent during the first 4 d following exposure can be expressed as an exponential function of the time from the termination of HBO: HVD = 28 + 72(1 - exp-0.053t) (t in hours). This information may be of importance in cases of repeated exposures to HBO where one tries to avoid cumulative damage to the carotid bodies, and in the care of the poorly oxygenated patient after HBO treatment. PMID- 1610339 TI - Changes in striatal and cortical amino acid and ammonia levels of rat brain after one hyperbaric oxygen-induced seizure. AB - Changes in amino acids (AA) and ammonia were investigated in the cerebral cortex and striatum of rats after the following conditions: 1) one hyperbaric oxygen (HBO)-induced seizure (6 ATA O2); 2) exposure to 6 ATA air; and 3) exposure to atmospheric pressure (no seizures in both latter groups). Exposure to 6 ATA air produced no change with respect to atmospheric pressure. After HBO seizure, AA levels (except for gamma-amino butyric acid, GABA, and glutamine), with respect to 6 ATA air levels, were altered in the striatum with a concomitant rise in ammonia (+70%) at variance with the cortex. These changes could be explained by increased oxidative deamination in the striatum. Decrease in taurine content ( 66%) in the striatum, where HBO lipoperoxidation exists, suggests an alteration of glial function leading to blockade of uptake and loss of released products in interstitial fluid. This pattern of change recalls the one seen in ischemic conditions, but cannot be confirmed in the absence of measurements of extracellular amino acid levels under HBO conditions. The maintenance in the level of GABA would favor its role in controlling seizure. In the cortex, only a few AA levels decreased, along with a nonsignificant trend for ammonia to increase. The remaining abnormalities in the striatum, after the first HBO seizure, may explain the already known repetition of seizures in continuously exposed animals and are consistent with previous data on the important role of the striatum. PMID- 1610340 TI - Intraventricular conduction disturbances in civilian flying personnel: left anterior hemiblock. AB - We undertook a retrospective study of the natural history, clinical significance, prognosis, associated conduction disturbances, and pathology, as well as flying fitness qualification of 247 cases of left anterior hemiblock (LAH), detected in a presumably healthy population of 8,915 male individuals engaged in civilian flying activities (prevalence: 2.77%). The cases were divided into three groups according to the electrical axis value of the first electrocardiogram (ECG). The group with the slow mode of appearance of LAH was the most common. If associated with right bundle branch block, LAH usually evolves first. LAH could not be ascribed to any definite pathology; neither was it a forerunner of left bundle branch block nor complete atrioventricular block. Not one episode of syncope nor of sudden incapacitation was reported. As a mere ECG finding, LAH does not modify an aviator's fitness qualification. If another conduction disturbance develops, qualification will depend on the results of complementary studies, non-invasive or invasive, according to any associated conduction disturbance. PMID- 1610341 TI - The incidence of myopia in the Israel Air Force rated population: a 10-year prospective study. AB - It is important to define the risk in pilots of becoming myopic in order to determine the need for yearly screening, and to predict pilot eligibility in environments where the use of corrective lenses may present problems. We conducted a prospective study of 1400 air force personnel followed for 10 years, who could be divided into three major groups; those with 20/20 vision in both eyes, those with 20/25 in one eye only and whose vision was 20/20 using both eyes together, and those who were accepted despite the fact that they required corrective lenses. Over the 10-year period, 23.1% of those with 20/25 visual acuity in one eye needed corrective lenses, significantly more than the 7.4% observed in those with 20/20 vision in both eyes (relative risk 3.1, 95% confidence interval 2.2-4.3, p less than 0.0000). The prevalence of corrective lenses increased until age 26. We conclude that 7.4% of pilots will become myopic over a 10-year period if accepted with 20/20 vision in both eyes. The risk, however, is much higher in those with incipient growth myopia starting in one eye at entry. Therefore, the annual screening of visual acuity in air force personnel is essential. PMID- 1610342 TI - Cataract surgery and intraocular lenses in military aviators. AB - We reviewed the medical records of 23 military aviators who were evaluated by the United States Air Force School of Aerospace Medicine (USAFSAM) after cataract extraction with intraocular lens implantation between 1979 and 1990. The 23 subjects were male Caucasians, with a mean age of 43 years. Of the subjects, 21 were pilots, and, of these, 8 were qualified in high-performance aircraft. There were a total of 28 operated eyes, 24 of which had received extracapsular cataract extractions (ECCE) with posterior chamber lenses. The best-corrected, postoperative vision was 20/20 or better in all eyes. Posterior capsule opacification occurred in 14 (60%) of the ECCE eyes, with five requiring Nd:YAG (Yttrium-Aluminum-Garnet) laser capsulotomies. One aviator was disqualified from flying duties because of ocular deficiencies, for a visually-qualified-to-fly rate of 96%. Eight aviators have actually flown since surgery. Although follow-up was short, the initial results are encouraging. PMID- 1610343 TI - The revised trauma score: a means to evaluate aeromedical staffing patterns. AB - The myriad of crew configurations used in the transport of patients by aeromedical services have not been subject to objective measures of patient status before and after transport as a means of evaluating their contribution to patient care. This work reviews the outcomes of 96 patients cared for by aeromedical crews composed of two dual-licensed registered nurse (RN)/paramedics (PM) or one registered nurse and one paramedic. The Revised Trauma Score for Triage (RTS) was used as an objective measure of patient status. There were no significant differences between the crew configurations in ground time, flight time, total mission time, and RTS after transport; initial RTS in patients cared for by 2 RN/PM crews was significantly lower. Analysis of the subset of patients felt to be more severely injured (RTS less than or equal to 10) failed to show any significant differences between these two groups. This work outlines a methodology that objectively assesses the contribution of different crew configurations to the care of the trauma patient. PMID- 1610344 TI - Cases from the aerospace medicine residents' teaching file. Case #50. A student Army aviator with hypersensitivity pneumonitis. PMID- 1610345 TI - Cloning of the guinea pig 5-lipoxygenase gene and nucleotide sequence of its promoter. AB - The guinea pig 5-lipoxygenase (5-LO) gene and its promoter were cloned from a guinea pig genomic DNA library. Sequencing analysis of the guinea pig promoter revealed that expression of the 5-LO gene in this rodent is probably governed by cis acting nucleotide sequences quite similar to the human gene. Nucleotide sequences that bind factors like Sp-1, AP-2, NF-kB and c-Ha-ras were identified in the guinea pig 5-LO promoter region. PMID- 1610346 TI - Glycation of MP26 and MP22 in bovine lens membranes. AB - Alkali treated membranes were isolated from mature bovine lenses and incubated with different sugars for 3 weeks to study the effect of glycation on the lens intrinsic membrane proteins, MP26 and MP22. The obtained results show that a) [1 14C] ascorbic acid (ASA) was able to glycate the intrinsic membrane proteins as rapidly as soluble lens proteins; b) on 15% acrylamide gels in SDS, glucose, fructose, galactose and ribose exhibited low activity for crosslinking membrane proteins; whereas ASA, dehydroascorbate (DHA), diketogulonate (DKG), xylosone and threose, all showed not only the formation of protein multimers, but also highly crosslinked products, which did not enter the spacer gel; c) except glycated MP22, all of the crosslinks of MP26 or MP22, and also the glycated MP26, showed cross reactivity with polyclonal MP26 antibody; d) the extent of crosslinking correlated with an equal loss of lysine and arginine contents by amino acid analysis. PMID- 1610347 TI - Cloning and expression of the human 5-HT1B-type receptor gene. AB - We report the cloning and expression of a novel 5-HT receptor gene from human genomic DNA. This clone, HGCR1, contains an apparently intronless open reading frame of 390 amino acids with the seven hydrophobic regions, typical of G-protein coupled receptors. The deduced amino acid sequence of HGCR1 is 39%, 55% and 87% identical to that for the human 5-HT1A, the human 5-HT1D and the rat 5-HT1B receptor, respectively. [3H]5-HT binding to transfected COS-7 cell membranes yields a pharmacological profile similar to that of 5-HT1B receptor. Thus these findings indicate the presence of 5-HT1B-type receptor in the human. PMID- 1610348 TI - Phosphorylation of interleukin-6 at serine54: an early event in the secretory pathway in human fibroblasts. AB - The cytokine interleukin-6 (IL-6) is the major phosphoprotein secreted by human fibroblasts induced with interleukin-1 alpha (IL-1 alpha). We have determined that Ser54 is the predominant site of phosphorylation on the fibroblast-derived IL-6 polypeptide; the amino acid motif surrounding this site is reminiscent of the target site for the Golgi-associated protein (casein) kinase. It has been shown earlier that the IL-6 polypeptide follows the classical secretory pathway where N-linked glycosylation is detectable within the first 15 minutes of labeling with [35S]-methionine and O-linked glycosylation occurs between 15-30 minutes after the start of polypeptide synthesis. Pulse-chase experiments using [32P]-orthophosphate or [35S]-methionine as tracers indicated that phosphorylation of IL-6 occurred prior to its O-glycosylation suggesting that the de novo synthesized IL-6 polypeptide is rapidly, perhaps even cotranslationally, phosphorylated at an intravesicular site (in the endoplasmic reticulum and/or Golgi). When IL-1 alpha-induced fibroblasts were exposed to cycloheximide there was enhancement of the net de novo synthesis and secretion of IL-6 as followed by [35S]-methionine labeling ("superinduction") but the secreted cytokine was no longer phosphorylated as monitored by [32P] labeling. Thus, phosphorylation of the IL-6 polypeptide is not an obligatory requirement for secretion of this cytokine. Furthermore, IL-6 phosphorylation is inhibited by cycloheximide through a mechanism different from the drug's effects on polypeptide synthesis per se. PMID- 1610349 TI - The primary structure of rat ribosomal protein L8. AB - The amino acid sequence of the rat 60S ribosomal subunit protein L8 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L8 has 257 amino acids and has a molecular weight of 28,007. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 4 or 5 copies of the L8 gene. The mRNA for the protein is about 950 nucleotides in length. Rat L8 is homologous to ribosomal proteins from other eukaryotes and to proteins from eubacterial, archaebacterial, and chloroplast ribosomes. PMID- 1610350 TI - Copper-metallothionein induction in the liver of LEC rats. AB - Recently, copper (Cu) was found to be unusually accumulated, suggesting the induction of metallothionein (MT) in the liver of LEC rats (Long-Evans rats with a cinnamon-like coat color), which develop spontaneous jaundice with hereditary hepatitis. Thus, the direct relationship between the unusual Cu accumulation and the induction of Cu-MT was investigated by giving LEC rats Cu-overloaded or Cu deficient diets. Results based on the determinations of Cu and MT levels in several organs, as well as the gel-filtration profiles of the cytosols of liver homogenates, showed that dietary Cu induced Cu-MT and development of hepatic injury associated with jaundice. PMID- 1610351 TI - Heparan sulphate proteoglycans are involved in the lipoprotein lipase-mediated enhancement of the cellular binding of very low density and low density lipoproteins. AB - We found that LPL enhances the binding to HepG2 cells and fibroblasts of both VLDL and apoE free LDL. In the presence of 1.7 micrograms/ml of purified bovine LPL, the binding of LDL and VLDL was up to 60 fold increased as compared to the control binding. In addition, LPL enhances the binding in LDL-receptor negative fibroblasts to the same extent as it does in normal fibroblasts. The presence of 10 mM of EGTA could not prevent the LPL-mediated enhancement of the binding of both LDL and VLDL to fibroblasts, indicating that the binding is calcium independent. Furthermore, up- and down regulation of the LDL receptor did not influence the binding of these lipoproteins in the presence of LPL. Strikingly, we found that the enhancing effect of LPL on the binding of LDL and VLDL to HepG2 cells could be abolished by preincubation of the cells with heparinase, suggesting that heparan sulphate proteoglycans are involved in the LPL-mediated stimulation. We hypothesize that the enhancement of the cellular binding of LDL and VLDL in the presence of LPL is caused by an LPL-bridging between proteoglycans present on the plasma membrane and the lipoproteins, and that the LDL receptor and LRP are not involved. PMID- 1610352 TI - Polymorphisms of human cholesterol 7 alpha-hydroxylase. AB - Human liver cholesterol 7 alpha-hydroxylase (CYP7) cDNAs were isolated from a human liver cDNA library. A full-length cDNA has 2901 nucleotides which encode a typical P450 polypeptide of 504 amino acid residues. Two different sequences of codon 100, TTT (Phe) and TCT (Ser), were identified in cDNA clones. In addition, codons 347 and 385 are GAT (Asp) and GAC (Asp) in all cDNA clones, whereas those reported previously (FEBS Lett. 268, 137-140, 1990) are AAT (Asn) and AGC (Ser), respectively. Since there is only one 7 alpha-hydroxylase gene in the human genome, it is likely that polymorphisms at the codon 100 of cDNA clones arise from two different alleles in the 7 alpha-hydroxylase gene of this human liver. PMID- 1610353 TI - Partial purification of phosphoramidon-sensitive endothelin converting enzyme in porcine aortic endothelial cells: high affinity for Ricinus communis agglutinin. AB - A membrane-bound endothelin converting enzyme (ECE) of porcine aortic endothelial cells (ECs) was solubilized with Lubrol PX with high efficiency and stability. The solubilized ECE was bound to Ricinus communis agglutinin (RCA) but not to peanut agglutinin (PNA) or wheat germ agglutinin (WGA), suggesting that the ECE has a galactosylated structure possessing a high affinity for RCA. The sequential chromatography on RCA-agarose, PNA-agarose and a TSKgel DEAE-5PW column attained 2,100-fold purification for the ECE over the membrane fractions. The purified ECE was sensitively inhibited by phosphoramidon but not by thiorphan. The present RCA and PNA affinity column procedures may be a powerful approach to isolation of ECE of EC origin. PMID- 1610354 TI - Effects of endogenous soluble beta-galactoside binding lectins and protein inhibitor of fucosyltransferase on the enzymes involved in the intestinal fucosylation process. AB - Soluble beta-galactoside binding lectins were prepared from the rat small intestinal mucosa by chromatography on asialofetuin-Sepharose. The lectin fraction exhibits 3 bands with Mr of 21,5 kDa, 19 kDa and 17 kDa on SDS-PAGE. This fraction inhibits a partially purified soluble alpha(1-2)-fucosyltransferase by interaction with the glycoprotein substrate asialofetuin, whereas the inhibition is non competitive for the donor GDP-fucose. It has no effect on other enzymes of the fucosylation system, namely glycosyl-nucleotide pyrophosphatase and the system synthesizing GDP-fucose from GDP-mannose. A different and specific soluble protein inhibitor of fucosyltransferase activity inhibits this activity by a competitive mechanism for GDP-fucose and a non competitive one for asialofetuin. Unlike the lectins, this inhibitor also inhibits the action of pyrophosphatase and the formation of GDP-fucose by different mechanisms. The possible extension of these in vitro results to the in vivo regulation of glycosylation is discussed. PMID- 1610355 TI - The potassium channel opener BRL 38227 inhibits binding of [125I]-labelled endothelin-1 to rat cardiac membranes. AB - Binding of [125I]-labelled endothelin-1 (ET-1) to rat cardiac membranes and the effects of endothelin-1 (ET-1), endothelin-3 (ET-3), the calcium channel antagonist nifedipine, and both enantiomers of the potassium channel opener cromakalim (BRL 34915) on binding have been examined. Specific binding of [125I] ET-1 was inhibited in a concentration dependent manner by both unlabelled ET-1 (10(-12)-10(-7) M) and ET-3 (10(-12)-10(-6) M). Nifedipine (10(-11)-10(-5) M) did not affect [125I]-ET-1 binding. However, BRL 38227 (10(-11)-10(-5) M), the biologically active isomer of cromakalim, significantly inhibited [125I]-ET-1 binding. The inactive isomer, BRL 38226 (10(-11)-10(-5) M) had no effect. These findings provide the first evidence for a stereospecific interaction between BRL 38227 and an ET-1 binding site in rat cardiac membranes. PMID- 1610356 TI - 1,25-Dihydroxyvitamin D effects in the kidney: induction of calmodulin binding proteins. AB - A marked induction of 125I-calmodulin binding proteins (185kDa and 115kDa) occurred in the rat kidney in response to treatment with 1,25-dihydroxyvitamin D3 (100 ng/day s.c. x 7d). These 125I-calmodulin binding proteins, measured by the gel overlay procedure, exhibited calcium dependence and were abolished in the presence of excess unlabelled calmodulin. The response was tissue specific: there was no change in 125I-calmodulin binding in rat testis, heart, and brain and only a modest elevation of binding to one calmodulin binding protein in the intestinal mucosa. These results are particularly important in suggesting that the calmodulin signal transduction mechanism may, via changes in its acceptor proteins, participate in mediating some biological effects of 1,25 dihydroxyvitamin D3. PMID- 1610358 TI - Molecular cloning and chromosomal assignment of human calbindin-D9k. AB - Human calbindin-D9k, the vitamin D-dependent calcium binding protein, has been cloned and sequenced following initial amplification of intestinal cDNA sequences by the polymerase chain reaction using mixed oligonucleotide primers. The derived amino acid sequence of 79 residues has a calculated molecular weight of 9015 and is 89% homologous with the bovine and porcine sequences. Probing DNA from human rodent somatic cell hybrids mapped human calbindin-D9k to chromosome Xp. A single abundant mRNA transcript was detectable in proximal small intestine but not in kidney, uterus or placenta. PMID- 1610357 TI - Functional co-expression of human oxidoreductase and cytochrome P450 1A1 in Saccharomyces cerevisiae results in increased EROD activity. AB - A cDNA coding for human oxidoreductase (NADPH-cytochrome P450 reductase) was expressed in S. cerevisiae on a high copy plasmid under control of a constitutive promoter. Microsomes from a transformed strain lacking endogenous oxidoreductase exhibited cytochrome c reductase activity. An apparent Km of 7.3 microM for the substrate NADPH was determined. Expression of human oxidoreductase complemented a mutation in the yeast oxidoreductase gene CPR1 and fully reversed the ketoconazole sensitive phenotype of the respective strain. The 7-ethoxyresorufin O-deethylase activity of yeast cells expressing human cytochrome P450 1A1 was increased by more than sixteen-fold upon coexpression of human oxidoreductase. These results strongly suggest that a more efficient coupling between the human enzymes might be responsible for the increase in enzyme activity. PMID- 1610359 TI - Interleukin-3 induces translocation and down-regulation of protein kinase C in human platelets. AB - Protein kinase C (PKC) is a family of phospholipid-dependent kinases that is involved, along with calcium mobilization, in the activation of human platelets. Since interleukin-3 (IL-3) has been shown to act, in part, by activating PKC, we investigated the effect of IL-3 on PKC activity and content in human platelets. Exposure of platelets to 10 ng/ml of IL-3 was associated with a rapid (i.e., within 3 minutes) translocation of PKC activity and content from the cytosol to the membrane fraction. In addition, treatment with IL-3 effected a time-dependent down-regulation of PKC activity and content. We speculate that IL-3 may act as a modulator of PKC-dependent pathways in the human platelet. PMID- 1610360 TI - Pre-translational induction of pentoxyresorufin O-depentylase by pyridine. AB - Pentoxyresorufin O-depentylase activity, mainly associated with phenobarbital inducible cytochrome P450IIB1 (designated CYP2B1), was increased after a single treatment of pyridine (250 mg/kg, i.p.), and further increased by repeated treatments for 5 days. The catalytic activity and immunoreactive protein of CYP2B recognized by polyclonal antibodies were significantly induced by a relatively high dose of pyridine (250 mg/kg, i.p.) while ethanol-inducible cytochrome P450IIE1 (CYP2E1) could be induced by a low dosage (25 mg/kg, i.p.). Unlike CYP2E1 induction without changing its mRNA level, the induction of CYP2B by pyridine was accompanied by an elevation of its mRNA, indicating a pre translational activation of this enzyme. These results indicate that pyridine induces various isozymes of cytochromes P450 by different induction mechanisms. PMID- 1610361 TI - Differential expression of angiotensin II receptor subtype mRNAs (AT-1A and AT 1B) in the brain. AB - Two highly similar rat angiotensin II, type 1 receptor cDNAs (AT1) have been described that probably are encoded by separate genes. AT1A subtype mRNA was expressed in vascular smooth muscle whereas AT1B mRNA was expressed in adrenal and pituitary. Here we measured the two AT1 subtype mRNAs in brain using reverse transcriptase/polymerase chain reactions. AT1B mRNA was predominant in subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), the two regions that mediate angiotensin II-induced drinking behavior, and also in cerebellum. AT1A mRNA was predominant in the hypothalamus. Thus, the two AT1 receptor subtypes established to reside in peripheral tissues also are found in the central nervous system where the AT1B subtype may mediate drinking behavior. PMID- 1610363 TI - Cloning and overexpression of the Lactobacillus bulgaricus NAD(+)-dependent D lactate dehydrogenase gene in Escherichia coli:purification and characterization of the recombinant enzyme. AB - The Lactobacillus bulgaricus NAD(+)-dependent D-lactate dehydrogenase gene was amplified by the polymerase chain reaction and cloned into an Escherichia coli expression plasmid pKK223.3. Attempts to clone the full-length chromosomal DNA encoding D-lactate dehydrogenase from a partial Sau3AI lambda phage library or an enriched clone bank in E. coli were unsuccessful. The recombinant plasmid pKBULDH containing the amplified gene overexpressed D-lactate dehydrogenase (greater than 30% of total soluble protein) following induction of the tac promotor with isopropyl-beta-D-thiogalactopyranoside. The cloned gene product was purified to homogeneity by two chromatographic steps with 76% recovery of enzyme activity. All the properties of the recombinant protein, e.g., optimum pH and temperature, Km and k(cat) for pyruvate as well as for other 2-oxo acids and the subunit structure were identical to the wild-type enzyme. PMID- 1610362 TI - Butylated hydroxytoluene prevents cumene hydroperoxide-induced Ca2+ release from liver mitochondria by inhibiting pyridine nucleotide hydrolysis. AB - The mechanism by which the free radical scavenger butylated hydroxytoluene (BHT) prevents cumene hydroperoxide-induced Ca2+ release from rat liver mitochondria was studied. In Ca(2+)-loaded mitochondria cumene hydroperoxide induced a rapid oxidation and subsequent hydrolysis of the pyridine nucleotides. In the presence of BHT, pyridine nucleotide oxidation by cumene hydroperoxide occurred but was reversible as hydrolysis was prevented by BHT. However, the addition of BHT directly to rat liver submitochondrial particles did not inhibit NAD+ hydrolysis or the formation of ADP-ribose from NAD+. Thus, whilst BHT prevented NAD+ hydrolysis in isolated mitochondria, this appeared not to be due to a direct effect of BHT on the NADase. It is concluded that the mechanism of action of BHT on cumene hydroperoxide-induced Ca2+ release from mitochondria involves the inhibition of pyridine nucleotide hydrolysis by an indirect mechanism rather than the radical scavenging properties of BHT. PMID- 1610364 TI - 20-Hydroxyeicosatetraenoic acid is excreted as a glucuronide conjugate in human urine. AB - 20-hydroxyeicosatetraenoic acid, a major renal P-450 metabolite of arachidonic acid, has been quantified in human urine using capillary gas chromatography/electron capture negative ion chemical ionization mass spectrometry. The urinary excretion of 20-hydroxyeicosatetraenoic acid was in the low pg/ml range. However, treatment of urine with beta-glucuronidase resulted in a 13- to 28-fold increase in its concentration. This suggests 20 hydroxyeicosatetraenoic acid differs from other eicosanoids in that it is excreted primarily as a glucuronide conjugate. PMID- 1610365 TI - Human brain peptidase activity with the specificity to generate the N-terminus of the Alzheimer beta-amyloid protein from its precursor. AB - The synthetic peptide acetyl-Glu-Val-Lys-Met-Asp-Ala-Glu-Phe-NH2, which spans the cleavage site (Met-Asp) required to generate the N-terminus of the Alzheimer beta amyloid protein from its precursor, was used to search for human brain peptidases which may be involved in this potentially amyloidogenic process. In both soluble and particulate fractions from human brain the primary cleavage point of the peptide was the Met-Asp bond. Purification and characterization of the activity from the soluble fraction showed that it was metalloendopeptidase 24.15 (EC3.4.24.15). This enzyme is therefore a candidate for the generation of the N terminus of beta-amyloid protein from its precursor. PMID- 1610366 TI - Calmodulin specifically binds three proteins of the dystrophin-glycoprotein complex. AB - Dystrophin is the approximately 400,000 Da. protein (p400K) product of the Duchenne muscular dystrophy gene locus. In the sarcolemma membrane, it is associated with several other proteins, many of which are glycoproteins (abbreviated gp) and include gp156K, p59K, gp50K, gp43K, gp35K, and p25K. Here, we show that dystrophin, gp156K, and p59K are calmodulin-binding proteins, the binding is Ca(2+)-dependent, and of high-affinity similar to that seen with calmodulin-activated enzymes. Two putative calmodulin-binding sequences were identified, one at either end of the dystrophin sequence. PMID- 1610367 TI - Concentrations and molecular forms of human brain natriuretic peptide in plasma. AB - Using a highly sensitive radioimmunoassay (RIA) system for human brain natriuretic peptide (BNP), immunoreactive (ir-) human BNP was found to be present in plasma, in addition to heart and brain tissue. Plasma concentrations of ir-BNP were 0.17-0.74 fmol/ml (mean: 0.35 fmol/ml) in normal young men, being about 1/17 of the plasma concentration of human atrial natriuretic peptide (ANP). In patients with heart disease, plasma concentration of ir-BNP increased about 100 fold (5.00-177.37 fmol/ml), being nearly comparable to that of ir-ANP, even though ANP concentration also increased about 7-fold. Two molecular forms of ir BNP in plasma were identified as BNP-32 and gamma-BNP (pro-BNP), which are also found in cardiac atrium. In normal human plasma, gamma-BNP is the predominant molecular form, while the main form in cardiac atrium is BNP-32. These results suggest that biosynthesis and secretion of BNP are augmented in heart disease and that human BNP has a unique processing and metabolic system distinct from that of ANP. PMID- 1610368 TI - 1H NMR studies on the oxidized ferredoxin from Clostridium pasteurianum. AB - The 8Fe-8S ferredoxin from Clostridium pasteurianum was investigated by 1D and 2D 1H NMR. Spectra of a well-structured, full native preparation of the oxidized protein in 1 M NaCl at pH 8.0 are presented. Assignments of non-isotropically shifted resonances in the diamagnetic region of the spectrum, namely those of the unique aromatic residues F30 and Y2, are presented for the first time. PMID- 1610369 TI - Micelles of poly(oxyethylene)-poly(oxypropylene) block copolymer (pluronic) as a tool for low-molecular compound delivery into a cell: phosphorylation of intracellular proteins with micelle incorporated [gamma-32P]ATP. AB - Pluronic P85 (poly(oxyethylene)-poly(oxypropylene) block copolymer) was used for in vitro delivery of [gamma-32P]ATP into intact Jurkat cells. Negatively charged ATP molecules are not able to penetrate cell plasma membrane. Hence, exogenous [gamma-32P]ATP added to a cell culture does not participate in phosphorylation of intracellular proteins. The addition to cells of [gamma-32P]ATP solubilized in positively charged (containing dodecylamine) pluronic micelles results in considerable increase of protein phosphorylation. In this case the treatment of intact cells with alkaline phosphatase (resulting in dephosphorylation of external proteins) causes no essential decrease of [32P]-incorporation in cell proteins. That gives an evidence of delivery of solubilized ATP into a cell. Under the experimental conditions used, pluronic micelles neither influence the viability of cells nor permeabilize cell plasma membrane. PMID- 1610370 TI - Isolation, crystallization in the macrogravitation field, preliminary X-ray investigation of uridine phosphorylase from Escherichia coli K-12. AB - Uridine phosphorylase (UPH) from Escherichia coli K-12 has been purified to near homogeneity from a strain harbouring the udp gene, encoding UPH, on a multicopy plasmid. UPH was purified to electrophoretic homogeneity with the specific activity 230 units/mg with a recovery of 80%, yielding 120 mg of enzyme from 3g cells. Crystals of enzyme suitable for X-ray diffraction analysis were obtained in a preparative ultracentrifuge. The packing of the molecules in the crystals may be described by the space group P2(1)2(1)2(1) with the unit cell constants a = 90.4; b = 128.8; c = 136.8 A. There is one molecule per asymmetric unit, Vm = 2.4. These crystals diffract to at least 2.5-2.7 A resolution. The hexameric structure of UPH was directly demonstrated by electron microscopy study and image processing. PMID- 1610371 TI - Biochemical changes induced by two new prophylactic regimens for cyanide antagonism. AB - Clinical efficacy of two pretreatment regimens, sodium nitrite (SN) + hydroxylamine (HA) and SN + 4-dimethylaminophenol (DMAP) were evaluated in rats by studying various biochemical variables at different time intervals. Animals given single subcutaneous (s.c.) co-administration of SN+HA or SN+DMAP showed significantly elevated levels of blood bilirubin indicating hemolytic anemia. Increased levels of blood creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and glutamic oxaloacetic transaminase (GOT) were indicative of aseptic necrosis at the injection site. On account of low methemoglobin reductase activity in human erythrocytes, a reduced sub-clinical dose of HA or DMAP is envisaged in humans. PMID- 1610372 TI - Phosphate free perfusion prevents washout of tissue creatine in Langendorff perfused rabbit heart. AB - Rabbit hearts were perfused with Krebs-Henseleit bicarbonate buffer supplemented with 15 mM glucose and 10 mU/ml of insulin +/- Pi. At the end of 60 min the hearts were freeze-clamped and the content of ATP, creatine phosphate, creatine, lactate, pyruvate, DHAP and 3-P glycerate were determined enzymatically in neutralized perchloric acid tissue extracts. The free cytosolic ADP and Pi and the cytosolic NAD+ redox and phosphorylation potentials were calculated from the measured metabolite concentrations. Pi free perfusion resulted in increased creatine, free cytosolic ADP and cytosolic phosphorylation potential, decreased calculated free Pi and no change in cardiac ATP and creatine phosphate content. The increase in the cytosolic phosphorylation potential was due to the lowering of cytosolic free Pi. The increase in ADP was due to the increase in creatine. The increase in creatine appeared to be due to an inhibition of creatine efflux from the heart during Pi free perfusion which was mediated by an enhanced Na+ electrochemical gradient. PMID- 1610373 TI - Impairment of L-arginine metabolism in spontaneously hypertensive rats. AB - Plasma L-arginine concentrations were determined in spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) before and after water immersion stress. There was no difference in the plasma levels of L-arginine before stress loading between SHR and WKY rats. A significant decrease in the L-arginine level was found in the adult SHR rats after the stress stimuli. However, there was no change in plasma levels of L-arginine in the adult WKY rats before and after water immersion stress. In the weanling rats, significant increases were observed in the plasma L-arginine levels after stress loading in both strains. These findings indicate that there may be an impairment of the L-arginine metabolism in the SHR rats with age and that it may involve in the genesis of hypertension in the SHR rat through the L-arginine-EDRF system. PMID- 1610374 TI - Differential inhibition of protein synthesis in reticulocyte lysates and wheat germ extracts by a protein isolated from wheat germ extracts. AB - A protein with a molecular mass of 35-37 kDa has been isolated and partially purified from the postribosomal supernatant of wheat germ by ammonium sulfate precipitation (60-90%), Sephadex G-75, and DEAE-cellulose chromatography. It inhibited endogenous protein synthesis in rabbit reticulocyte lysates but had no effect on translation in wheat germ extracts. At low concentrations (0.34-1.36 ng/15 microliter assay), inhibition was limited to initiation of peptide synthesis. At higher concentrations (13.6 ng/15 microliter assay), elongation was also suppressed. PMID- 1610375 TI - Nitrogen balance discrepancy in Wistar rats fed a cafeteria diet. AB - The nitrogen balance of Wistar rats aged 30-45 and 45-60 days fed either control or cafeteria diet has been determined by measuring the intake fecal and urinary excretion and nitrogen deposition in the body. The efficiency of extraction of dietary nitrogen was higher for cafeteria diet-fed rats, which showed a lower nitrogen excretion and higher body nitrogen accretion than controls. The accurate measurement of nitrogen intake, excretion and deposition showed a consistent proportion of nitrogen unaccounted for (10-26% of net intake) in the studied fractions, which proportion was higher in the youngest cafeteria diet-fed rats. PMID- 1610376 TI - Configuration of the 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid, an intermediate in the peroxisomal conversion of 3 alpha,7 alpha,12 trihydroxy-5 beta-cholestanoic acid to cholic acid in rat liver. AB - 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-enoic acid, formed in the peroxisomal oxidation of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoyl CoA by the THCA-CoA oxidase in rat liver, was isolated and purified on reverse phase HPLC. The configuration of the C-24/25 double bond was determined to be trans (E) by using 1H-NMR spectrometry. PMID- 1610377 TI - Preparation of soluble peptide libraries: application to studies of platelet adhesion sequences. AB - We describe chemical synthesis of peptide mixtures that equally express many sequence combinations. Using 65 couplings of single amino acids, five mixtures were prepared with the sequences Tyr-Gly-Arg-Gly-Yyy-Xxx-Xxx, where Yyy is Ser, Asp, Arg, Asn, or Glu, and Xxx is any amino acids. Compositional and sequence analyses supported full representation of all amino acids, except isoleucine was deficient in the sixth position. The data suggest formation of a repertoire of 1,900 sequence combinations (5 x 19 x 20). The mixture with Asp as the fifth residue inhibited platelet adhesion to fibronectin more effectively than the other mixtures. Peptide libraries offer a new tool for investigating bioactive peptides. PMID- 1610378 TI - Partial conversion of vasopressinyl-Gly-Lys-Arg into pharmacologically active vasopressin through secretory granule carboxypeptidase E and alpha-amidating processing enzymes. AB - Vasopressinyl-Gly-Lys-Arg, the first intermediate derived from vasopressin protein precursor, has been converted into mature vasopressin by an "in vitro" two-step reaction through neurohypophysial secretory granule enzymes. Whereas the conversion into vasopressinyl-Gly is virtually complete at pH 5.5 as judged by HPLC, the conversion of vasopressinyl-Gly into vasopressin is weak at pHs 6.0 or 8.0 as judged by HPLC and measure of generated pressor activity. It is suggested that the high conversion yield usually seen in mammalian neurohypophysis, where no intermediate is detected, might be due to additional "in vivo" factors such as particular membrane-association or binding of the intermediate onto a neurophysin carrier. PMID- 1610379 TI - Structural analysis and comparison of cobrotoxin and cardiotoxins by near-IR Fourier transform Raman spectroscopy. AB - Venom toxins were isolated from Formosan cobra (Naja naja atra) by cation exchange chromatography. The near-IR FT-Raman analytical method has been applied to the characterization and classification of the toxin components in their lyophilized forms. Structural analysis and comparison of various purified toxin fractions were made with respect to their amino acid compositions and near-IR Fourier-transform Raman spectra. The results indicate that the major secondary structure of cobra toxins including cobrotoxin and various cardiotoxins is mainly anti-parallel beta-pleated sheet as judged by the Raman signals at 1238 cm-1 (amide III) and 1671 cm-1 (amide I). It is also found that the relative Raman signal intensities of Tyr, Phe, Trp and Met residues in purified toxins correlate very well with the structural data obtained from amino acid analysis. The advantage and improvement of applying the near-IR FT-Raman spectroscopy to the unambiguous classification and comparison of venom toxins are evident and the discrepancies with previous Raman studies on these venom toxins are also revealed and discussed. PMID- 1610380 TI - Substrate specificity of a dicarboxyl-CoA: dicarboxylic acid coenzyme A transferase from rat liver mitochondria. AB - Substrate specificity of a dicarboxyl-CoA: dicarboxylic acids coenzyme A transferase purified from rat liver mitochondria was assayed. In addition to the previously identified substrates succinyl-CoA, 3-hydroxy-3-methylglutaryl-CoA and malonyl-CoA (Francesconi et al.(1989) Biochim. Biophys. Acta, 999, 163-170) also methylmalonyl-CoA, glutaryl-CoA and adipyl-CoA acted as enzyme substrates, with the latter thioester showing the highest apparent affinity. All corresponding dicarboxylic acids, but not oxaloacetic, citric, alpha-ketoglutaric, malic, fumaric and glutamic acids, acted as coenzyme A acceptor substrates. None of the tested monocarboxylic acids, or the corresponding coenzyme A esters, were enzymatically transformed by the here described coenzyme A transferase. PMID- 1610381 TI - Hyaluronic acid of human skin and post-burn scar: heterogeneity in primary structure and molecular weight. AB - Hyaluronic acid (HA) was isolated from the dermis and epidermis of normal human skin and from normal and hypertrophic scar tissue, and the molecular properties of this polysaccharide were studied by circular dichroism (CD) and high performance liquid chromatography. The molecular weights of HA of normal skin and post-burn scar tissue range from 62,000 to 180,000. Hexosamine analysis showed no galactosamine contamination and 0.37 to 2.2 w/w% of protein in the HA sample. Uronic acid analysis suggests a heterogeneous distribution of glucuronic and iduronic acids. The CD profiles of these samples are similar, indicating no significant conformational variations among them. These data suggest that the variation in the molecular properties of HA between skin and scar tissue may be due to diversity of embryonic origin between epidermis HA and dermis HA, and to the diversity of the wound-healing process between normal scar HA and hypertrophic scar HA. PMID- 1610382 TI - Identification, isolation and purification of neurotoxic phospholipases A2 from Vipera russelli venom using polyclonal antibodies. AB - All the neurotoxic phospholipases A2 present in whole Vipera russelli venom were precipitated selectively from other non-neurotoxic phospholipases A2 and non phospholipases A2 fractions using antibodies (anti PL-V Ig) raised against one of the purified neurotoxic phospholipases A2 (VRV PL-V). These neurotoxins were identified and isolated in their homogeneous form by chromatographic and electrophoretic methods. The present report of selective isolation and purification of all the neurotoxic phospholipases A2 of V. russelli venom is first of its kind. PMID- 1610383 TI - Erythrocyte carbonic anhydrase: a major intracellular enzyme to regulate cellular sodium metabolism in chronic renal failure patients with diabetes and hypertension. AB - Changes in carbonic anhydrase (CA) activity have been associated with metabolic diseases like diabetes mellitus and hypertension. To explore the exchange of H+ for Na+ and 22Na+, the sodium pool, CA activity and H2O content in erythrocytes from the two groups of diabetic chronic renal failure (CRF) patients with and without hypertension before dialysis were studied. The results were compared with those from the normotensive controls. The CA activity was determined spectrophotometrically, the sodium pool by ouabain insensitive 22Na+ influx and the percent H2O content gravimetrically. The 22Na+ influx in CRF patients with hypertension was significantly higher (p less than 0.025) than in the normotensive CRF patients and the controls. The levels of CA activity (U/min/mL) and the percent H2O content were significantly different in the hypertensive and the normotensive CRF patients from the control group (2.24 +/- 0.69 and 67.11 +/- 1.33, 1.95 +/- 0.63 and 66.43 +/- 1.51, 1.44 +/- 0.07 and 63.61 +/- 1.72, respectively). The present study implies a relationship between the 22Na+ influx and CA activity in CRF patients with hypertension. The variation of CA activity may thus result in changes in H+ production and ultimately in the intracellular Na+ pool. PMID- 1610384 TI - Gangliosides released by the perfused rat liver are associated to high density lipoprotein. AB - We examine here the delivery of gangliosides from the perfused rat liver into the perfusate. One hour after the administration of [3H]GM1 to recirculating perfused livers, almost 80% of the perfusate radioactive gangliosides were recovered associated to the HDL fraction. This fraction was relatively enriched in radioactive GD1a. The pattern of endogenous gangliosides from perfused livers, rat serum and perfusates were very different: GM3 was the main liver ganglioside, GM1 and GD1a were the most abundant in perfusates being GM3 almost absent; GM3, GM1 and GD1a were present in rat serum in similar proportions. Using a non recirculating perfusion protocol, radioactive gangliosides were found in the HDL fraction since 15 minutes after the administration of [3H]GM1. These results suggest that rat liver supplies the perfusates with some gangliosides and that they are associated to HDL. These facts arise the possibility that the liver is one of the source of serum gangliosides. PMID- 1610385 TI - Effects of androgen on phosphorylation of chromosomal proteins in mouse submandibular gland. AB - The effect of androgen on intranuclear distribution of androgen receptor binding sites was studied. The level of the androgen receptor complex in dinucleosomes increased 1 h after androgen treatment and those in the mono- and trinucleosomes increased 3 h after androgen treatment. Investigation by 32P incorporation into the nuclei and active chromatin showed that androgen resulted in an increase in the rate of phosphorylation at 3 h and reduced to the control level at 6 h. These data suggest that association of androgen receptor with the acceptor sites and activities of protein kinase in active chromatin are simultaneously stimulated for activating the transcription by androgen. PMID- 1610386 TI - Exercise-induced oxidant stress in the lung tissue: role of dietary supplementation of vitamin E and selenium. AB - Strenuous physical exercise in the form of swimming in female albino rats increased the oxidative reactions, probably leading to the generation of oxy-free radicals in the lung tissue. Free radical-mediated lipid peroxidation measured in the form of lipid peroxides increased in the pulmonary tissue in response to exhaustive exercise, indicating such a possibility. Dietary supplementation of vitamin E (Vit.E) and selenium (Se) for a period of 12 weeks reduced the oxidative reactions and the ensuing lipid peroxidation in the pulmonary tissue. Physical exercise in control animals induced the activity of superoxide dismutase (SOD), the superoxide anion radical (O2-.) quencher. However, the SOD levels in nutrient-fed animals at rest and after exercise remained well below the control levels, indicating the decreased generation of oxy-free radicals in them. Similarly, selenium-dependent glutathione peroxidase (Se-GSH Px), the enzyme involved in the reduction of organic and inorganic peroxides, and glutathione S- transferase (GST), the multifunctional protein involved in the detoxification of a number of xenobiotics, were increased in response to exercise in control animals, but were significantly decreased in nutrient-fed animals upon exercise. The induction of GST seems to be more towards the peroxidase activity of GST, i.e., non-selenium glutathione peroxidase (Non-Se-GSH Px), which is primarily involved in the reduction of endoperoxides. The studies thus indicate the induction of oxidative stress in the pulmonary tissue upon exhaustive physical exercise and the effectiveness of vit.E and Se independently and more so in combination in combating the exercise-induced oxidant stress. PMID- 1610387 TI - Microcalorimetric measurements of heat production in isolated rat brown adipocytes. AB - Heat production, oxygen consumption, and lipolysis in isolated interscapular brown adipocytes from the rat were investigated. Epinephrine, norepinephrine, and isoproterenol increased heat production in a concentration-dependent manner, showing, about 6-, 4-, and 5-fold higher effects than controls, respectively. The concentration of isoproterenol for threshold heat production and glycerol release were 10(-10) M and 10(-9) M, respectively. The fact that 10(-9) M isoproterenol increased heat production by about 3-fold while glycerol release had no effect at all indicates that calorimetry is more appropriate for investigation of brown adipocytes. At least the method is more sensitive than that of measuring glycerol release. PMID- 1610388 TI - A new potent inhibitor of horse liver alcohol dehydrogenase: p-methylbenzyl hydroperoxide. AB - A product of p-xylene auto-oxidation, p-methylbenzyl hydroperoxide, acts as a very strong reversible inhibitor of the ethanol dehydrogenating activity of horse liver alcohol dehydrogenase. Concentrations of hydroperoxide as low as that of the enzyme active site (about 10(-8) mol.dm-3) in the assay depresses the activity by 50%. Somewhat less potent is benzyl hydroperoxide (derived from toluene) while the (secondary) hydroperoxide derived from ethylbenzene and tert.butyl hydroperoxide and cumyl hydroperoxide do not inhibit HLAD appreciably. PMID- 1610389 TI - Free and membrane-bound lactate dehydrogenase from white driving muscles of skate. AB - Purified cytoplasmic and membrane-bound lactate dehydrogenases (LDH) from white muscle of skate were characterized, Km for pyruvate and NADH for purified LDH were 150 +/- 16 and 29 +/- 7 microM, and for membrane-bound LDH were 185 +/- 22 and 7.5 +/- 1.5 microM, respectively. The membrane-bound enzyme was not inhibited by high pyruvate concentration (up to 20 mM) in contrast to purified LDH. Part of membrane-bound LDH was released by incubation in solutions with a high level of KCl (up to 1 M) or at alkaline pH. The inactivation rate during trypsin digestion for solubilized LDH was 2-3-fold higher than that for the membrane-bound enzyme. PMID- 1610390 TI - Tissue lipids in experimental calcium oxalate lithiasis and the effect of DL alpha-lipoic acid. AB - The function of DL alpha-lipoic acid (6,8-thioctic acid) as a prosthetic group in the oxidative decarboxylation of alpha-keto acids, pyruvate and alpha ketoglutarate in mitochondria is well known. Its role is well extended to certain reactions in lipid biosynthesis. In addition, lipoic acid has been shown to prevent the induced precipitation of calcium oxalate crystals in the renal tissues of laboratory animals. Here, the effect of alpha-lipoic acid was studied, on altered tissue lipid levels manifested during experimental renal lithiasis. Raised tissue cholesterol, triglyceride and low phospholipid levels were some of the striking significant observations made in calculogenic rats. Lipoic acid treatment reduced tissue cholesterol and triglyceride levels significantly and raised phospholipids. The alterations may have a bearing in relation to calcium oxalate stone formation. PMID- 1610391 TI - Lipoprotein lipase enzyme expression in 3T3-L1 adipocytes is posttranscriptionally down-regulated by retinoic acid. AB - The effects of all-trans retinoic acid (RA) on the lipoprotein lipase (LPL) activity, synthesis and mRNA content in 3T3-L1 adipocytes were studied. When fully differentiated 3T3-L1 adipocytes were exposed to RA, dose-dependent suppression of LPL activity was observed. The loss of activity reached a maximum of 60% of the control level and appeared to be due to an effect on synthesis of the enzyme, as judged from the decreased incorporation of [35S] methionine and [35S] cysteine into immunoprecipitable LPL. The LPL mRNA level remained unchanged under the same conditions. In contrast, no significant reduction in glycerol-3 phosphate dehydrogenase activity or change in the morphological signature occurred on 24 hr exposure of 3T3-L1 adipocytes to RA. These results suggest that RA can specifically down-regulate LPL enzyme expression in adipocytes at the posttranscriptional level. PMID- 1610392 TI - Photomodulation of the nucleating activity of a photocleavable crosslinked actin dimer. AB - The ability to generate substrate concentration jumps through photo-deprotection of amine, carboxyl and phosphate groups has been an important development for investigations of protein activity in complex systems. To broaden the versatility and applications of photo-deprotection techniques for the photomodulation of protein activity we describe the synthesis and characterisation of a reagent for generating free thiol from thioether groups and a related photocleavable, heterobifunctional crosslinking reagent. Chemical and spectroscopic studies of a model thiol protected derivative were used to show some features of thiol group photodeprotection. To demonstrate how the photocleavable crosslinking reagent may be used to modulate the activity of proteins we investigated the effect of light on the nucleating activity of crosslinked actin dimer; thus following near ultraviolet irradiation of the actin dimer the crosslink was cleaved, presumeably at the thioether bond, resulting in the concomitant dissociation of dimer, loss of nucleating activity and creation of a concentration jump of polymerisable G actin monomer. On the basis of this initial study we discuss applications and limitations of these reagents for the photomodulation of protein activity in vitro and in vivo. PMID- 1610393 TI - The high mobility group of nuclear proteins as biomarkers of age and caloric restriction in rats. AB - The quantitative levels and phosphorylation states of the high mobility group (HMG) of proteins were investigated in bone marrow, brain, heart, kidney, liver, pancreas, spleen, testis and thymus of three groups of male Fischer 344 rats. Two groups of rats, young ad libitum (Y/AL - 1 1/2 mo.) and old ad libitum (O/AL - 28 mo.), had free access to rat chow, and a third group of old rats were maintained on a caloric restricted intake (O/CR - 28 mo.). The quantities of HMGs 1,2,14 and 17 were significantly reduced in O/AL rats compared with Y/AL rats in all tissues examined, and in many cases, the amount of HMGs of O/CR rats were increased by varying degrees from O/AL animals. In G2-phase nuclei of bone marrow, spleen and testis, phosphorylation of HMG proteins was reduced significantly in O/AL rats, but was enhanced in O/CR animals (especially HMG14). These levels of HMGs in O/CR animals, altered by age and diet dependent factors, reflect a condition which is more reminiscent of Y/AL than O/AL animals. PMID- 1610394 TI - DNA ligase I mRNA and enzyme levels in human hematopoietic cells under dimethyl sulfoxide-induced growth-arrest and differentiation. AB - About half the activity level of DNA ligase I in cycling human lymphoblastoid cells (Raji and Akata) remained in the cells arrested at G1 by a 4-day treatment with 1.5% dimethyl sulfoxide (DMSO), and one-third the enzyme activity in actively growing promyelocytic leukemia cells HL-60 was detected in the terminally differentiated cells after DMSO-treatment. In contrast, DNA ligase I mRNA was negligible in the G1-arrested Raji and differentiated HL-60 cells. The steady-state mRNA level was increased 9 h after release from DMSO in the G1 arrested Raji cells and reached a maximum at 18 h. These results indicate that gene expression of human DNA ligase I, but not activity level of the enzyme, is closely correlated with activity of cell proliferation. PMID- 1610395 TI - Steroid receptor structure and antihormone drug design. PMID- 1610396 TI - Reduction by clofibric acid of serum arachidonic acid in rats. Effect on the acyl composition of renal phospholipids. AB - Alterations induced by p-chlorophenoxyisobutyric acid (clofibric acid) in the composition of phosphatidylcholine and cholesterol esters in serum and their influence on the composition of phosphatidylcholine in the kidney were studied. Rats of different ages responded differently to the drug in terms of the levels of arachidonic acid (20:4) and linoleic acid (18:2) in the phosphatidylcholine and cholesterol esters in the serum. Administration of clofibric acid to 26-week old rats for 2 weeks caused a marked decreased in the relative level of 20:4 in phosphatidylcholine and cholesterol esters in serum, whereas similar treatment of 6-week-old rats resulted in a reduction of 18:2 and, to a lesser extent, of 20:4 in serum lipids. The decrease in phosphatidylcholine that contained 20:4 in the serum of old rats was mainly due to a decrease in the concentration of stearoyl arachidonoyl (18:0-20:4) species. The decrease in cholesterol arachidonate in serum caused by the treatment of old rats with clofibric acid seemed to be due to a reduction in the relative level of serum phosphatidylcholine containing 20:4. The marked reduction in serum lipids that contained 20:4 caused a decrease in the relative level of 20:4 in renal phospholipids, in particular, a decrease in the proportion of palmitoyl-arachidonoyl (16:0-20:4) and 18:0-20:4 phosphatidylcholine. PMID- 1610397 TI - Characterization of muscarinic cholinergic receptors in intact myocardial cells in vitro. AB - Muscarinic acetylcholine receptors (mAChR) were studied on heart cells grown in culture by the radioligand binding technique. We used [3H]n-methyl-scopolamine to monitor the level of receptors on intact cardiocytes. The number of mAChR was very low during the first days in culture (23 fmol/dish). It increased gradually until it reached a plateau on the 4th day (180 fmol/dish), where it remained for 1-2 weeks. To determine whether contractile activity affected the level or affinity of mAChR, the cardiocytes were exposed to agents that stimulate or arrest the heart beat. Treatment with triiodothyronine (T3, 10-90 nM) for 48 hr caused a reduction in the level of the receptors by 20-30% without changing significantly the affinity of the receptors. Similarly, electrical stimulation caused a reduction in the level of the receptors by 30-40%, without a significant influence on creatine kinase activity. When the myocardial cells were treated with Ca-channel blocker such as metoxyverapamil (D600) (10-30 micrograms/mL) or diltiazem (10-25 micrograms/mL) the level of the receptors was also reduced by 30 40%. The reduction in the receptor binding sites was accompanied by an increase in Kd from 0.8 to 3.2 nM in D600-treated cells, whereas there was no significant change in the radioligand affinity after application of diltiazem. Treatment with D600 or T3 together with cycloheximide showed that under these experimental conditions the rate of receptor degradation was accelerated. The half-life of the receptors in the control was 27 hr, whereas the half-lives of T3 and D600 were 15 and 18 hr, respectively. It is concluded that regulation of the amount of cholinergic receptors occurs at the level of receptor breakdown, and simple linkage does not exist between the rate of cardiac contractions and the number of mAChR. PMID- 1610398 TI - Differential inhibition of hepatic morphine UDP-glucuronosyltransferases by metal ions. AB - The major metabolites of morphine, morphine-3-glucuronide (M3G) and morphine-6 glucuronide (M6G), possess significant pharmacological properties. Whilst both metabolites bind to mu-opioid binding sites, M6G is a potent agonist whereas M3G antagonizes some of the effects of morphine and M6G. An inter-species comparison of in vitro hepatic morphine processing was performed. The results showed that not all species were able to produce M6G whereas all those tested did produce M3G. Guinea-pig liver produced the greatest amounts of M6G and was therefore chosen as a model to study morphine glucuronidation in further detail. Inclusion of the detergent Brij 58 (0.33 mg/mg protein) and Mg2+ (15 mM) in the standard assay incubation gave optimal production of both M3G and M6G by guinea-pig liver homogenates. A number of metal ions were investigated for their ability to inhibit glucuronidation of morphine in both the 3- and 6-positions. Some metal ions, namely Cu+, Cu2+ and Cd2+, were able to inhibit the production of M3G without affecting glucuronidation at the 6-position. Taken together, these data provide further evidence for the existence of UDP-glucuronosyltransferase isoenzymes responsible for the metabolism of morphine. In addition these isoenzymes can be differentially modulated and therefore it is possible to alter the ratio of M3G:M6G formed during in vitro metabolic studies. PMID- 1610399 TI - Ebselen. Antioxidant capacity in renal preservation. AB - Ebselen (PZ51) was tested for its ability to inhibit oxidative membrane damage and improve outcome of rabbit kidneys rendered cold ischaemic for 72 hr. In view of the rapid metabolism of ebselen, the antioxidant capacities of its two principal metabolites were first compared with that of the parent drug in an in vitro hepatic microsomal lipid peroxidation system initiated by NADPH/Fe(3+)-ADP. The potent antioxidant activity of ebselen was confirmed but metabolite I (2 glucuronylselenobenzanilide) exhibited no antioxidant potential up to a concentration of 50 microM; metabolite II (4-hydroxy-2-methyl-selenobenzanilide) did inhibit lipid peroxidation but was about 80 times less effective than the parent compound. The storage of rabbit kidneys in hypertonic citrate solution at 0 degrees for 72 hr of cold ischaemia resulted in greatly increased susceptibility to oxidative membrane damage in both the cortex and medulla as determined by the subsequent in vitro formation of two markers of lipid peroxidation (Schiff's bases and thiobarbituric acid-reactive material). Inclusion of ebselen (50 microM) in the flush and storage solution led to a highly significant reduction in these oxidative markers in both regions of the kidney. Intracellular and interstitial oedema was noted in organs subjected to 72 hr cold ischaemia and was reduced by ebselen (50 microM in the flush/storage solution). The rate of post-ischaemic lipid peroxidation was found to correlate well with the extent of oedema in the renal medulla (r = 0.84, P less than 0.001) but no such correlation was found in the cortex. Administration of ebselen (5.5 mg/kg i.v. and 100 microM in the flush/storage solution) did not improve the long term survival of rabbits following autotransplantation of a single kidney stored for 48 or 72 hr. No protective effect of ebselen could be demonstrated either in terms of graded physiological function or histological outcome. PMID- 1610400 TI - Photosensitizing efficiency of two regioisomers of the benzoporphyrin derivative monoacid ring A (BPD-MA). AB - Benzoporphyrin derivative, monoacid ring A (BPD-MA), currently in clinical trials as a photosensitizer for photodynamic therapy for cancer, consists of two regioisomers (A1 and A2) present in equal proportions. The contribution of the regioisomers to the overall photosensitizing potency of BPD-MA was tested in vitro and in vivo. The in vitro photosensitizing potencies of BPD-MA-A1 and -A2 were tested in a standard cytotoxicity assay using M1 (rhabdomyosarcoma of DBA/2 mice) tumor cells and were found to be equivalent. The in vivo photosensitizing efficacies of the regioisomers were tested in the M1 tumor model in DBA/2 mice and were also found to be equivalent. Biodistribution of the regioisomers in mouse plasma, tumor and liver was studied in M1 tumor-bearing DBA/2 mice at 15 min and 3 hr post intravenous injection of [14C]BPD-MA-A1/A2 at 4 mg/kg body weight. Plasma and extracts from tumor and liver were analysed by HPLC and tested for radioactivity. The two regioisomers were eliminated from plasma and liver at different rates, which resulted in A1:A2 ratios of 1:0.28 in plasma and 1:0.75 in liver at 3 hr post injection. The differential elimination was not observed to any significant degree in the tumor, where even at 3 hr post injection the A1:A2 ratio was 1:1.15. Therefore, we concluded that in tumor tissue, at 3 hr post injection, the time at which laser photodynamic therapy is carried out, both regioisomers were present in about equal proportions. Further, both regioisomers were fully active as determined by an in vitro cytotoxicity assay following extraction. PMID- 1610402 TI - Methotrexate transport in the human intestine. Evidence for heterogeneity. AB - The transport of methotrexate (MTX) was investigated in organ-cultured endoscopic biopsy specimens of intestinal mucosa from normal subjects. In biopsy specimens from the proximal small intestine incubated with [3H]MTX (0.1 microM) for 2 hr at pH 5.5, [3H]MTX accumulated in the intracellular fluid to a concentration 3.5 fold higher than that of the medium, but at pH 6.5 and 7.5, the concentration was the same as that of the medium. In biopsy specimens from the cecum incubated under similar conditions, no accumulation against a concentration gradient was found. However, the accumulation of MTX was significantly higher at pH 5.5 than at 7.5. At [MTX] = 0.1 microM, the initial rate of MTX transport in the small intestine was significantly affected by medium pH and was optimal at pH 5.5. The relationship between the initial rate of uptake and medium [H+] was hyperbolic, suggestive of saturability with respect to [H+] with a Km of 132.2 nm [H+], corresponding to a medium pH of 6.88. At medium [MTX] = 10 microM, this effect was abolished. At pH 5.5, the relationship between the initial rate of uptake and medium [MTX] was sigmoidal, suggestive of a positive cooperativity, with napp of 1.8. [MTX] at 0.5 Vmax was 20.37 microM. Folic acid inhibited 37% of MTX flux. At pH 7.5, the relationship between the initial rate of uptake of MTX and medium [MTX] was linear. These data indicate the presence of a proton-dependent active transport of MTX in the human proximal small intestine, which is partially shared with folic acid. PMID- 1610401 TI - Porphyrogenic properties of the terpenes camphor, pinene, and thujone (with a note on historic implications for absinthe and the illness of Vincent van Gogh). AB - Camphor, alpha-pinene (the major component of turpentine), and thujone (a constituent in the liqueur called absinthe) produced an increase in porphyrin production in primary cultures of chick embryo liver cells. In the presence of desferrioxamine (an iron chelator which inhibits heme synthesis and thereby mimics the effect of the block associated with acute porphyria), the terpenes enhanced porphyrin accumulation 5- to 20-fold. They also induced synthesis of the rate-controlling enzyme for the pathway, 5-aminolevulinic acid synthase, which was monitored both spectrophotometrically and immunochemically. These effects are shared by well-known porphyrogenic chemicals such as phenobarbital and glutethimide. Camphor and glutethimide alone led to the accumulation of mostly uro- and heptacarboxylporphyrins, whereas alpha-pinene and thujone resulted in lesser accumulations of porphyrins which were predominantly copro- and protoporphyrins. In the presence of desferrioxamine, plus any of the three terpenes, the major product that accumulated was protoporphyrin. The present results indicate that the terpenes tested are porphyrogenic and hazardous to patients with underlying defects in hepatic heme synthesis. There are also implications for the illness of Vincent van Gogh and the once popular, but now banned liqueur, called absinthe. PMID- 1610403 TI - Nitric oxide production in endotoxin-resistant C3H/HeJ mice stimulated with flavone-8-acetic acid and xanthenone-4-acetic acid analogues. AB - The production of nitric oxide in endotoxin-resistant C3H/HeJ mice in response to flavone-8-acetic acid (FAA), derivatives of xanthenone-4-acetic (XAA), endotoxin and recombinant human tumour necrosis factor-alpha (TNF-alpha) was investigated and compared with the induction of haemorrhagic necrosis in subcutaneous M16/C tumours. FAA and XAA analogues stimulated nitric oxide production both in vitro (activated macrophages) and in vivo (plasma nitrate elevation) in both C3H/HeJ and C3H/HeN mice (5,6-dimethyl-XAA greater than 5-methyl-XAA greater than FAA greater than XAA greater than 8-methyl-XAA). Recombinant human TNF-alpha stimulated nitric oxide production equally from both murine strains while endotoxin stimulated nitric oxide production only by C3H/HeN mice. The extent of induction of haemorrhagic necrosis in tumour-bearing mice treated with FAA, 5,6 dimethyl XAA or endotoxin paralleled the effects on nitric oxide production, showing a differential between the two strains of mice only in the case of endotoxin. PMID- 1610404 TI - Expression of hepatic microsomal cytochrome P450s as altered by uremia. AB - The proportions of different hepatic microsomal cytochrome P450s expressed in uremic rats were studied with specific antibodies and with a steroid hydroxylase assay. In male uremic rats, the hepatic levels of P450 2C11, a male-specific form, and 3A2, a male-dominant form, were decreased to about 30% at 5 weeks after the induction of uremia. These changes were paralleled by decreases in the activities of testosterone 2 alpha-, 16 alpha-, and 6 beta-hydroxylation. The level of P450 2A1, abundant in immature rats, was increased 2-fold by uremia and accompanied by an increase in testosterone 7 alpha-hydroxylation activity. The levels of P450 2C6 and 2E1 were not changed by uremia. The levels of male specific and male-dominant forms such as P450 2C11 and 3A2 are affected by the serum level of testosterone, which was decreased in the male rats with uremia. Therefore, castrated rats were prepared to compare the effects of testosterone on hepatic cytochrome P450s in uremic rats with those in castrated rats. When testosterone was administered to the castrated rats, the decreased levels of both P450 2C11 and 3A2 returned to normal. However, the administration of testosterone to the uremic rats did not prevent the decrease in the levels of these P450s. In female rats, changes in the levels of cytochrome P450s were not as great during uremia as those in male uremic rats. The level of P450 2C12, a female-specific form, was not changed; the level of P450 2A1 was increased by 50%, that of 3A2 which is barely detected in female rats was increased by 60%, and that of 2E1 was increased by 25%. These results suggested that the changes in the hepatic levels of cytochrome P450s were affected by factors other than testosterone in uremic rats. PMID- 1610405 TI - Muscarinic receptor subtypes in human and rat colon smooth muscle. AB - Muscarinic receptor subtypes in human and rat colon smooth muscle homogenates were characterized with [3H]N-methylscopolamine ([3H]NMS) by ligand binding studies. [3H]NMS saturation experiments show the existence of a homogeneous population of non-interacting binding sites with similar affinity (KD values of 1.38 +/- 0.20 nM in human colon smooth muscle and 1.48 +/- 0.47 nM in rat colon smooth muscle) and with Hill slopes close to unity in both samples of tissue. However, a significant (P less than 0.01) increase in muscarinic receptor density (Bmax) is found in human colon (29.9 +/- 2.9 fmol/mg protein) compared with rat colon (17.2 +/- 1.5 fmol/mg protein). Inhibition of [3H]NMS binding by non labelled compounds shows the following order in human colon: atropine greater than AF-DX 116 greater than pirenzepine. Whereas in rat colon the rank order obtained is atropine greater than pirenzepine greater than AF-DX 116. Atropine and pirenzepine bind to a homogeneous population of binding sites, although pirenzepine shows higher affinity to bind to the sites present in rat colon (Ki = 1.08 +/- 0.08 microM) than those in human colon (Ki = 1.74 +/- 0.02 microM) (P less than 0.05). Similarly, IC50 values obtained in AF-DX 116 competition experiments were significantly different (P less than 0.01) in human colon (IC50 = 1.69 +/- 0.37 microM) than in rat colon (IC50 = 3.78 +/- 0.75 microM). Unlike atropine and pirenzepine, the inhibition of [3H]NMS binding by AF-DX 116 did not yield a simple mass-action binding curve (nH less than 1, P less than 0.01) suggesting the presence of more than one subtype of muscarinic receptor in both species. Computer analysis of these curves with a two binding site model suggests the presence of two populations of receptor. The apparent Ki1 value for the high affinity binding site is 0.49 +/- 0.07 microM for human colon smooth muscle and 0.33 +/- 0.05 microM for rat colon smooth muscle. The apparent Ki2 for the low affinity binding site is 8.01 +/- 1.0 microM for human samples and 6.07 +/- 1.1 microM for rat samples. These values are close enough to suggest that the first subtype of muscarinic receptor may be considered cardiac (M2) and the second subtype glandular (M3). The relative densities of the receptor subtypes are significantly different for both species. Human colon samples show the major densities of subtype M2, 22.62 +/- 1.11 fmol/mg protein, this represents 75.66 +/ 3.73% of the total receptors.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1610407 TI - In vitro protection of acetylcholinesterase and butyrylcholinesterase by tetrahydroaminoacridine. Comparison with physostigmine. AB - The protective action of 1,2,3,4-tetrahydro-9-aminoacridine (THA) against the long-lasting inactivation of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) brought about by diisopropylfluorophosphate (DFP) and physostigmine, as well as by neostigmine in the case of AChE only, was evaluated by a dilution technique using Electrophorus electricus AChE and horse serum BuChE as target enzymes. In parallel experiments, the ability of physostigmine itself to protect these enzymes from DFP was evaluated and compared with that of THA. THA pretreatment was seen to prevent in a dose-dependent manner the inhibition of both AChE and BuChE. However, it was appreciably more potent towards AChE than towards BuChE. THA mean EC50 values for protecting AChE against 10, 40 and 100 microM DFP were 0.04, 0.16 and 0.45 microM, respectively; against 1 microM physostigmine the value was 1.8 microM and against 1.2 microM neostigmine it was 3.0 microM. The THA mean EC50 value for protecting BuChE against 3 microM physostigmine was 0.55 microM and the values for protecting against 3, 10 and 40 microM DFP were 1.5, 3 and greater than 10 microM, respectively. The protective action of THA was time independent: recovery of the maximal enzymic activity was immediate upon dilution. Unlike THA, the protective action of physostigmine developed progressively after dilution and was maximal within 3-4 (AChE) or 6-8 hr (BuChE). Under our experimental conditions, 0.3 microM physostigmine protected approximately 70% of AChE from 40 microM DFP and 5 microM physostigmine protected 9 and 47% of BuChE from 40 and 3 microM DFP, respectively. The results of this work suggest that THA exerts its protective action by shielding the active site of AChE and BuChE from the attack of the inactivating agents on account of its higher enzymic affinity, whereas the protective action of physostigmine against DFP takes advantage also of the carbamylation of the enzyme. These results are in line with the hypothesis that protection of AChE is the primary mechanism responsible for the antidotal action of THA against organophosphorus poisoning. PMID- 1610406 TI - Effect of chronic hypoxia on detoxication enzymes in rat liver. AB - Studies were performed to determine the effects of chronic hypoxia on enzymes that catalyze various detoxication reactions. Rats were exposed to room air or 10.5% O2 for 10 days, and microsomes and postmicrosomal supernatants were isolated from liver. Detoxication enzyme activities were measured by radiochemical and spectrophotometric assays, and immunoreactive protein amounts were measured by Western blot analysis. Total cytochrome P450, as measured by the CO-difference spectrum, and activities of superoxide dismutase (EC 1.15.1.1), epoxide hydrolase (EC 4.2.1.63), catalase (EC 1.11.1.6), glutathione disulfide reductase (EC 1.6.4.2), and glutathione (GSH) S-transferase (EC 2.5.1.18) were not affected by this extent of hypoxia. In contrast, 10 days of hypoxia decreased activities or immunoreactivities (% of aerobic) of GSH peroxidase (EC 1.11.1.9) (54%), cytochrome P450EtOH2 (42%), CYP3A1 (53%), sulfotransferase (EC 2.8.2.1) (77%) and UDP-glucuronosyltransferase (EC 2.4.1.17) (65%). Activity of glucose-6 phosphate dehydrogenase (EC 1.1.1.49), an important enzyme in NADPH production was also decreased to 56% of the aerobic value, but Western blot analysis showed that the amount of protein reactive with antibodies to glucose-6-phosphate dehydrogenase was not affected by hypoxia. Thus, hypoxia may decrease activity of enzymes by regulatory mechanisms even though the amount of immuno-detectable enzyme is unchanged. Liver cells isolated from rats exposed to hypoxia also gave lower GSH synthetic rates than cells from normoxic rats. This result, together with the effect of hypoxia on glucose-6-phosphate dehydrogenase, indicates that the GSH supply for GSH-dependent detoxication reactions may be limited due to chronic hypoxia. To test directly whether chronic hypoxia increased sensitivity to a compound normally detoxified by a GSH-dependent reaction, sensitivity to tert-butyl hydroperoxide (t-BuOOH) of hepatocytes from rats exposed to in vivo hypoxia was compared to that from normoxic rats. The results showed that the cells from the hypoxic rats were much more sensitive to injury. Taken together, these results suggest that decreases in amounts and/or activities of detoxication enzymes during chronic hypoxia may result in increased susceptibility of cells to chemical injury. PMID- 1610408 TI - In vitro effects of valproate and valproate metabolites on mitochondrial oxidations. Relevance of CoA sequestration to the observed inhibitions. AB - The inhibitory effects of valproate (VPA) and nine of its metabolites on mitochondrial oxidations have been investigated. Valproate, 4-ene-VPE, 2,4-diene VPA and 2-propylglutaric acid inhibited the rate of oxygen consumption by rat liver mitochondrial fractions with long- and medium-chain fatty acids, glutamate (+/- malate), succinate, alpha-ketoglutarate (+ malate) and pyruvate (+ malate) as substrates. Sequestration of intramitochondrial free CoA by valproate and these three metabolites has been demonstrated and quantified. However, CoA trapping could not account for all the inhibitions observed. 2-ene-VPA and 3-oxo VPA, metabolites formed during the beta-oxidation of valproate, were not capable of trapping intramitochondrial CoA although they were inhibitors of the beta oxidation of decanoate, probably by inhibition of the medium-chain acyl-CoA synthetase. PMID- 1610410 TI - Prevention of binding of rgp120 by anti-HIV active tannins. AB - Several tannins with anti-HIV activity have been described previously (Nonaka et al., J Nat Prod 53: 587-595, 1990). We have shown that the tannins chebulinic acid and punicalin were able to block the binding of HIV rgp120 to CD4. These compounds were not toxic to stimulated human peripheral blood lymphocytes at concentrations ten times above their maximal effective concentration. PMID- 1610409 TI - Identification of human liver aldehyde dehydrogenases that catalyze the oxidation of aldophosphamide and retinaldehyde. AB - Biotransformation of the biologically and pharmacologically important aldehydes, retinaldehyde and aldophosphamide, is mediated, in part, by NAD(P)-dependent aldehyde dehydrogenases catalyze the oxidation of the aldehydes to their respective acids, retinoic acid and carboxyphosphamide. Not known at the onset of this investigation was which of the several known human aldehyde dehydrogenases (ALDHs) catalyze these reactions. Thus, human liver aldehyde dehydrogenases were chromatographically resolved and the ability of each to catalyze the oxidation of retinaldehyde and aldophosphamide was assessed. Only one, namely ALDH-1, catalyzed the oxidation of retinaldehyde; the Km value was 0.3 microM. Three, namely ALDH-1, ALDH-2 and succinic semialdehyde dehydrogenase, catalyzed the oxidation of aldophosphamide; Km values were 52, 1193, and 560 microM, respectively. ALDH-4, ALDH-5 and betaine aldehyde dehydrogenase did not catalyze the oxidation of either aldophosphamide or retinaldehyde. ALDH-1 and succinic semialdehyde dehydrogenase accounted for 64 and 30%, respectively, of the total hepatic aldehyde dehydrogenase-catalyzed aldophosphamide (160 microM) oxidation. ALDH-1-catalyzed oxidation of aldophosphamide was noncompetitively inhibited by chloral hydrate; the Ki value was 13 microM. ALDH-2- and succinic semialdehyde dehydrogenase-catalyzed oxidation of aldophosphamide was relatively insensitive to inhibition by chloral hydrate. These observations strongly suggest an important in vivo role for ALDH-1 in the catalysis of retinaldehyde and aldophosphamide biotransformation. Succinic semialdehyde dehydrogenase-catalyzed biotransformation of aldophosphamide may also be of some in vivo importance. PMID- 1610411 TI - Stimulation of insulin secretion by glucose in the absence of diminished potassium (86Rb+) permeability. AB - Two inhibitors of the nucleotide-sensitive K+ (KATP) channel, tolbutamide and quinine, were utilized in order to assess the role of this channel in glucose stimulated insulin release from perifused rat islets. In the absence of these drugs, the addition of 15 mM glucose elicited a marked biphasic stimulation of insulin secretion concomitant with a reduction in the rate of 86Rb+ efflux. In the presence of either 500 microM tolbutamide or 100 microM quinine, a reduced rate of efflux of 86Rb+ was observed together with an elevated rate of insulin release. Under such conditions, the addition of 15 mM glucose retained the ability to stimulate insulin secretion though this was associated with a marked increase in 86Rb+ efflux. It is concluded that a net reduction in beta-cell K+ permeability is not an obligatory step in glucose-stimulated insulin release. Thus, glucose is likely to exert depolarizing actions on the beta-cell in addition to the closure of K+ channels. PMID- 1610412 TI - Effects of the antidepressant/antipanic drug phenelzine on GABA concentrations and GABA-transaminase activity in rat brain. AB - The effects of long-term (28-day) administration of several antidepressant/antipanic drugs [imipramine, desipramine, tranylcypromine and phenelzine (PLZ)] on gamma-aminobutyric acid-tranaminase (GABA-T) activity and GABA levels were investigated in rat frontal cortex. Of the drugs investigated, only PLZ inhibited GABA-T and elevated GABA levels. Additional short-term experiments were conducted with PLZ, and they demonstrated a dose-dependent inhibition of GABA-T in rat whole brain. Time-response studies on inhibition of GABA-T in whole brain demonstrated that at a dose of PLZ of 15 mg/kg i.p. inhibition of GABA-T remained relatively constant from 1 to 8 hr and that the enzyme was still inhibited by 23% at 24 hr after PLZ administration. PMID- 1610413 TI - Pharmacokinetics of diltiazem absorption in the rat gastrointestinal tract. AB - The absorption of diltiazem (CAS 42399-41-7) from the stomach, small intestine, and colon of the rat has been studied, using an in situ cannulation procedure. Diltiazem solutions (1 mg/ml) were prepared in isotonic buffers at pH 3.5 (stomach), 6.2 (small intestine), or 7.5 (colon). 10 ml of drug solution was used in the small intestine, 4 ml was used in the stomach and colon. Aliquot (100 microliters) of the solution was withdrawn at 5-min intervals for a period of 30 min, and assayed by HPLC. A semilog plot of percent remaining vs. time showed that absorption followed apparent first order kinetics with absorption rate constant, ka, equal 0.07 min-1, 0.02 min-1, and 0.01 min-1, in the small intestine, colon, and stomach, respectively. PMID- 1610414 TI - Antihypertensive effects of verapamil, captopril and their combination at rest and during dynamic exercise. AB - In order to investigate the antihypertensive effects of verapamil (CAS 52-53-9) and captopril (CAS 62571-86-2), administered alone or in combination therapy, the blood pressure and heart rate effects of these two drugs at rest and during dynamic exercise were evaluated in a double blind study in 30 moderate or severe essential hypertensive patients. After a 30-day placebo wash-out period, 15 patients (age 60.6 +/- 8.0 years, mean +/- SD) were allocated to verapamil sustained-release treatment (120 mg b.i.d. for the first month of therapy and 240 mg b.i.d. for the second one) and 15 patients (age 58.4 +/- 10.0 years) to captopril treatment (25 mg b.i.d. and 50 mg b.i.d. for the first and second month of therapy, respectively). At low dosage both verapamil and captopril significantly (p less than 0.001) and markedly reduced blood pressure values. Goal diastolic blood pressure of 90 mmHg was achieved in 40% and 20% of patients in the verapamil group and in the captopril group, respectively, at high dosage. In contrast to captopril, verapamil induced a significant and dose-dependent heart rate reduction and markedly attenuated the pressor and tachycardiac responses to dynamic exercise. The combination of verapamil 240 mg b.i.d. plus captopril 50 mg b.i.d. was then administered to patients, whose blood pressure was not satisfactorily controlled by monotherapy. This regimen allowed a better blood pressure control both at rest and during exercise than on monotherapy and induced a complete blood pressure normalization in 62% of patients.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610415 TI - Comparative efficacy of vinpocetine, pentoxifylline and nicergoline on red blood cell deformability. AB - Using two different filtration methods for evaluating red blood cell deformability, the comparative effects of single oral doses of vinpocetine (CAS 42971-09-5; 10 mg), pentoxifylline (300 mg) and nicergoline (20 mg) were evaluated in 5 healthy volunteers. Out of the three agents only vinpocetine appeared to increase red blood cell deformability significantly. Thus vinpocetine was the most active drug tested and warrants further investigation in circulatory conditions characterized by a decrease in red cell deformability. PMID- 1610417 TI - Antinociceptive properties of thiamine, pyridoxine and cyanocobalamin following repeated oral administration to mice. AB - Following repeated oral administration for 7 days thiamine (thiamine nitrate, CAS 532-43-4), pyridoxine (pyridoxol hydrochloride, CAS 58-56-0), and cyanocobalamin (CAS 68-19-9) exhibited at high dose levels alone or in combination dose-related antinociceptive properties in the writhing test in the mouse. Cyanocobalamin exerted a potentiating effect in the combination of the 3 vitamins. PMID- 1610416 TI - Effect of glimepiride on the electrical activity of isolated rabbit heart muscle. AB - The effect of glimepiride (CAS 93479-97-1) on the electrical threshold, conduction time, effective refractory period and automaticity of left atrium and right ventricle in the isolated rabbit heart was investigated and compared with those of chlorpropamide and glibenclamide. From the sulphonylureas investigated only glibenclamide diminished the electrical activity of rabbit heart muscle preparations. Chlorpropamide and glimepiride have a mild effect to change the basic parameters on the opposite direction. It seems that glimepiride does not have a significant effect on cardiac muscle in vitro. PMID- 1610419 TI - Comparative pharmacokinetics and bioavailability study of percutaneous absorption of diclofenac from two topical formulations containing drug as a solution gel or as an emulsion gel. AB - In a 3-way cross-over study on 12 healthy adult volunteers, the percutaneous absorption of diclofenac (CAS 15307-79-6) was studied for two topical formulations containing 1% diclofenac. The relative bioavailability from the test formulation (a solution gel) in terms of Cmax and AUC, calculated from the amount of drug reaching the systemic circulation, was found to be twice the amount after application of reference product (an emulsion gel). The maximum concentration of the drug, from both topical formulations reaching the blood after cutaneous absorption was less than 10% of that obtained after the parenteral administration, which indirectly is indicative that adverse effects normally related to high drug blood concentrations, such as reached after oral administration, are unlikely to be experienced. PMID- 1610418 TI - Influence of limonene and laurocapram on percutaneous absorption of nonsteroidal anti-inflammatory drugs. AB - The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution. PMID- 1610420 TI - Synthesis and pharmacology of some new carbamodithioic acid esters. AB - In this study 13 new dithiocarbamates were prepared by reacting 3-methyl-6 chloroacetyl-benzoxazolinone with potassium N,N-disubstituted dithiocarbamate derivatives. The structures of the compounds were confirmed by UV, IR, 1H-NMR, mass spectroscopic methods and elementary analysis. The anticholinergic activity was tested on rabbit ileum. With exception of one compound all derivatives exhibited a stronger antihistaminic activity as compared with their anticholinergic action. PMID- 1610421 TI - Mucolytic effects of domiodol in tracheostomized patients after total laryngectomy. Double-blind, placebo-controlled, randomized pilot study with four month follow-up. AB - The results obtained in a controlled clinical trial aimed at evaluating the efficacy and tolerability of a mucolytic treatment in laryngectomized patients are described. Domiodol (Mucolitico Maggioni, CAS 61869-07-6), an organic iodinated mucolytic agent, was given at the dosage of 60 mg t.i.d. to 20 patients in the post-operative period after laryngectomy (average 2 weeks in hospital and 4 months follow-up at home). A matched series of patients received a placebo during the hospital period and no treatment after discharge. The patients receiving the active treatment showed a statistically and clinically significant improvement of respiratory parameters (cough intensity, sputum quantity, sputum quality, expectoration difficulty). Such improvement was earlier and greater than that observed in the placebo-treated patients. It is concluded that a mucolytic treatment may be helpful in the post-operative treatment of laryngectomized patients with permanent tracheostomy. PMID- 1610422 TI - [Clinical studies on acid inhibition by ranitidine given simultaneously with pentagastrin]. AB - In recent years there have been some reports of tolerance occurring in man with the antisecretory effect of H2 antagonists. We, therefore, studied the effect of 300 mg and 600 mg ranitidine (CAS 66357-35-5) daily and increasing i.v. doses of pentagastrin (0.37 microgram/kg, 0.75 microgram/kg, and 1.5 micrograms/kg body weight) on gastric acid output (mmol HCl/30 min) in 9 healthy volunteers. The study design was double-blind, randomized and cross-over. Pentagastrin stimulation was performed on day 1, day 8, and day 16. Increasing i.v. doses of pentagastrin induced an almost identical enhancement of volume secretion, total acid output as well as titratable acidity on the 3 study days. A 16-days treatment period with 300 mg and 600 mg ranitidine led to 80% and 90% inhibition of pentagastrin stimulated acid output. The degree of inhibition evoked by 300 mg and 600 mg ranitidine against pentagastrin was not statistically different during the 16-days treatment period; i.e. no significant tolerance did occur within 16 days. Our data suggest that, in contrast to intragastric acidity measurements, no significant decline of inhibitory effectiveness of ranitidine against i.v. pentagastrin could be observed in healthy male volunteers. PMID- 1610423 TI - In vitro inhibition of cytochrome P-450 reductases from pig liver microsomes by garlic extracts. AB - The activity of microsomal NADPH-cytochrome-P-450-reductase and NADH-cytochrome b5-reductase are inhibited after the addition of an aqueous extract of a pharmaceutical preparation of garlic (Allium sativum, L.) to buffer-suspended microsomes. Incubation of garlic extract with isolated pig liver microsomes also decreases the activity of cytochrome P-450-dependent ethoxycoumarin deethylation. As measured by malondialdehyde release, the effects on the enzyme system are evidently not due to lipid peroxidation. No loss of cytochrome P-450 pigment is observed. Moreover, it could be shown that addition of garlic extract displays no protective effect on microsomal lipids when oxidation occurs spontaneously or is enforced by short-wave UV-irradiation. The above findings were reproduced after applying a HPLC-purified preparation of alliin to the incubation mixtures, suggesting that alliin is the active principle for the inhibitory effects observed in vitro. PMID- 1610424 TI - Hypocholesterolemic effect of khellin and methoxsalen in male albino rats. AB - Khellin (CAS 82-02-0) and methoxsalen (CAS 298-81-7) were examined in male albino rats to evaluate their ability to modify serum lipoprotein cholesterol. Clinical chemistry parameters were also measured to obtain information indicative of possible drug toxicity. The drugs were evaluated in four-week double dose studies. After four weeks at 0.45 mg/100 mg b.wt. for khellin and 0.27 mg/100 g b.wt. for methoxsalen, per day, both drugs significantly lowered low density lipoprotein cholesterol, high density lipoprotein cholesterol and total cholesterol. Very low density lipoprotein cholesterol and triglycerides were not changed. No apparent toxicity was observed as clinical chemistry parameters and body weights were not different compared to control values. Similar results were observed with a lower dose of khellin (0.23 mg/100 g b.wt./d). A dose of 0.13 mg/100 g b.wt./d of methoxsalen had no observable effect in this study. Confirmation of the hypocholesterolemic activity of khellin and methoxsalen in this study enhances the therapeutic potential of these compounds against atherosclerosis. PMID- 1610425 TI - Absorption of ascorbic acid from a film-coated tablet and from a new enteric coated pellet preparation in subjects with inadequate plasma levels of ascorbic acid. AB - The effects of a film-coated tablet and a novel enteric-coated pellet preparation of ascorbic acid (CAS 50-81-7) on the plasma concentration and on the urinary excretion of ascorbic acid were investigated. The pharmacokinetic properties of these dosage forms were also compared both after a single dose and in steady state. The study was carried out as a randomized, single blind parallel group trial in 11 volunteers with inadequate plasma levels of ascorbic acid. The duration of the treatment period was 7 days. After the first dose, higher plasma ascorbic acid concentration as well as AUC and Cmax values were achieved with the film-coated preparation. After the multiple dosing in steady state, plasma ascorbic acid concentration as well as AUC and Cmax values were higher with the new pellet preparation. In addition, the plasma ascorbic acid concentration remained on higher level with pellet preparation on the 7th day. Tmax values for the pellet preparation were also slightly higher on both of the pharmacokinetic test days. The amount of ascorbic acid excreted in urine was higher with the film coated tablet. According to the results of this study it can be supposed that during the long-term supplementation the more complete absorption can be achieved with the new enteric-coated pellet preparation. PMID- 1610426 TI - [The effect of the calf spleen and calf thymus extracts, thymopentin and tuftsin, on the phagocytosis activity of neutrophilic granulocytes]. AB - In the present in vitro study, the influence of proteolytic as well as untreated spleen and thymus extracts and, as a comparison, of biologically active peptides tuftsin and thymopentin on the phagocytic activities of human polymorphonuclear leukocytes was investigated. At a chosen concentration of 200 micrograms/ml, all products studied exhibited a significant stimulation of polymorphonuclear leukocyte activity, when lucigenin-amplified chemiluminescence was measured. This effect was considerably enhanced with tuftsin, thymopentin and spleen extract, compared to the thymus preparations. No difference in chemiluminescence was obvious between hydrolyzed and untreated thymus extracts. In parallel experiments, phagocytosis of opsonized zymosan was investigated by light microscopy. Using identical substrate concentrations, only spleen extract showed significant stimulation. This observation indicates that the investigated polymorphonuclear leukocyte activities may be caused by substrate-specific mechanism on the cellular level. PMID- 1610427 TI - Synthesis and structure-antimicrobial activity relationships of quaternary ammonium derivatives of perhydropyrrolo-[3,4-c]pyridine. AB - A large homologous series of quaternary ammonium derivatives of perhydropyrrolo[3,4-c]pyridine 5 was synthesized and tested for in vitro antibacterial activity against different Gram-positive and Gram-negative bacteria. Compounds 5 proved to be always more potent than benzalkonium chloride, taken as reference. Antibacterial activity, expressed as log 1/MIC, was found linearly related to lipophilicity up to C13-C14 homologs, where a break in the linear relationship was observed. PMID- 1610428 TI - Syntheses and antifungal activities of some 3-(2-phenylethyl)-5-substituted- tetrahydro-2H-1,3,5-thiadiazine-2-thiones. AB - Ten new 3-(2-phenethyl)-5-substituted-tetrahydro-2H-1,3,5-thiadiazine-2- thiones were synthesized by the reaction of phenylethylamine with carbon disulfide and potassium hydroxide, followed by formaldehyde and appropriate amino acids. The structures of these compounds have been confirmed by UV, IR, 1H-NMR and elementary analysis. The antifungal activities of the compounds were tested by tube dilution method against yeast-like fungi (Candida albicans, C. parapsilosis, C. stellatoidea and C. pseudotropicalis) and minimal inhibitory concentration (MIC) and minimal fungicidal concentration (MFC) values were determined. All compounds proved to be highly effective against yeast-like fungi (MFC range: 1.56 12.5 micrograms/ml). PMID- 1610429 TI - Balanced designs for multiple crossover studies. AB - Experimental situations are considered, in which t different treatments are administered to n cases (volunteers, patients, animals etc.) during p periods (p less than or equal to t) in a way that each of these cases receives p different treatments in sequence (crossover designs). In order to minimize the influence of carry-over effects the designs of the trials are constructed with regard to three conditions of balance: (a) Each case receives the same number of treatments, (b) each treatment is applied the same number of times in each period, and (c) each possible transition between two consecutive periods appears the same number of times during the experiment. The minimal numbers of cases are given for complete (p = t) and incomplete (p less than t) designs balanced according to all the above mentioned conditions. Furthermore, the designs themselves (plans of the experiments) are also listed for the minimal number of cases for 2 less than or equal to p less than or equal to t less than or equal to 10. PMID- 1610430 TI - Pharmacokinetics and distribution of recombinant erythropoietin in rats. AB - Pharmacokinetics and distribution of recombinant human erythropoietin (rh-EPO, Epoch, CAS 11096-26-7) were studied in rats. After intravenous administration, concentrations of rh-EPO in the plasma declined biexponentially. AUC increased proportionally with the dose. The half-life of a-phase was prolonged with increasing doses. The low volume (Vss) of the distribution of rh-EPO was 65-79 ml/kg, which indicate a mainly extracellular distribution of this drug. The half life of beta-phase was 1.98-2.7 h. The total body clearance was 18-21 ml/h/kg, and was independent of the dose. The renal clearance was much lower than total body clearance, suggesting that extrarenal clearance, presumably metabolism, plays a role in elimination. rh-EPO was eliminated by metabolism. The profiles of times vs concentration of radioactivity in the bone marrow and spleen, which are considered to be target tissues, were different from that of the plasma; namely bone marrow and spleen showed Cmax at 30 min after dosing, and this time, radioactivity in these tissues showed almost intact rh-EPO. At the dose of 0.1 micrograms/kg, the concentration in the bone marrow was about 2-fold higher than that of plasma, the concentration in the spleen was lower than that in the plasma 30 min after dosing of rh-EPO. The distributions of rh-EPO in both tissues were saturable. PMID- 1610431 TI - Rationing. PMID- 1610433 TI - Reduced spinal bone mass in patients with uterine cervical cancer. PMID- 1610432 TI - Regeneration of the spleen and splenic autotransplantation. PMID- 1610435 TI - Aneurysm repair in patients presenting with distal embolization. PMID- 1610434 TI - Role of adenosine in cardiac dysfunction. PMID- 1610436 TI - Life threatening 'epilepsy'. PMID- 1610437 TI - Failed hip replacements. PMID- 1610438 TI - Deciding whether to be a doctor. PMID- 1610439 TI - Proper definitions for lag phase in gastric emptying of solid foods. PMID- 1610440 TI - Stereoisomers. PMID- 1610441 TI - Epidurals: a comparison of approaches. PMID- 1610442 TI - Transport of live animals for slaughter. PMID- 1610443 TI - Does prostacyclin sensitize arterial baroreceptors? PMID- 1610444 TI - Cholecystectomy provides long-term symptom relief in patients with acalculous gallbladders. PMID- 1610445 TI - Balloon atrial septostomy via the umbilical vein. PMID- 1610446 TI - Potassium in the perioperative period. PMID- 1610447 TI - Passive smoking and otitis media with effusion. PMID- 1610448 TI - Hypothyroidism and thyroid antibodies in polymyalgia rheumatica. PMID- 1610449 TI - Orthopaedist as traumatologist. PMID- 1610450 TI - Radial tunnel syndrome. An investigation of compression neuropathy as a possible cause. PMID- 1610451 TI - Not against cheese alone. PMID- 1610453 TI - Reliability of the modified Rankin Scale. PMID- 1610452 TI - Correspondence re: G. J. Laroye and S. Minkin. The impact of mitotic index on predicting outcome in breast carcinoma: a comparison of different counting methods in patients with different lymph node status. Mod Pathol 4:456, 1991. PMID- 1610454 TI - Cocaine-associated abnormalities may not be causally related. PMID- 1610455 TI - 'A survey of complete denture prosthetics for the elderly, the handicapped and difficult patients'. PMID- 1610456 TI - 'Osseointegration and the edentulous predicament. The 10-year-old Toronto study'. PMID- 1610457 TI - Chronic fatigue syndrome. PMID- 1610458 TI - Ethical issues concerning the HIV status of physicians and patients. PMID- 1610459 TI - Vignettes in coronary care. PMID- 1610460 TI - Usefulness of nifedipine in acute myocardial infarction. PMID- 1610461 TI - Differentiation of digoxin-induced ST-segment changes from ischemia-induced ST segment depression during Holter monitoring. PMID- 1610462 TI - Myocardial infarction prediction by artificial neural networks. PMID- 1610463 TI - Venous air embolism and the prone position. PMID- 1610464 TI - 'Neurological' complications of extradural bupivacaine. PMID- 1610465 TI - Prison medicine. PMID- 1610466 TI - Women's health: potential for better co-ordination of services. PMID- 1610467 TI - Looking for bovine spongiform encephalopathy. PMID- 1610468 TI - Alfred the Great: a diagnosis. PMID- 1610469 TI - Retroperitoneal venous anatomy. PMID- 1610470 TI - Noninvasive differentiation of noncoronary from coronary cardiomyopathy. PMID- 1610471 TI - Inconsistency of data linking the ryanodine receptor and malignant hyperthermia genes. PMID- 1610472 TI - Pharmacist work activity before and after pharmacy department computerization. AB - The effects of a dedicated computer system on pharmacists' daily activities at a 363-bed hospital were studied. A one-group pretest-posttest design was used. Twenty-four pharmacists recorded activity frequency and time for seven consecutive days several months before and after a pharmacy computer system was implemented. The computer system could be used for printing unit dose fill lists and i.v. labels, entering data, and printing patient profiles. An admissions, discharge, and transfer interface between the hospital system and the pharmacy system was also operational. The data were organized into 28 activities for analysis. For seven activities that were considered directly affected by computerization, a net 0.1-minute increase in the average time was found. Four of those seven showed an increase in average time (a total of 1.86 minutes): (1) calculating the composition of total parenteral nutrient or i.v. solution, (2) compounding large-volume i.v. solution, (3) profiling orders, and (4) checking the work of pharmacy technicians. The other three showed a decrease in average time (a total of 1.76 minutes): (1) preparing syringe or small-volume i.v. solution, (2) monitoring drug profiles, and (3) dispensing unit dose medications. However, with all 28 activities considered, a 1.03-minute decrease occurred in the average time per activity. Installation of a dedicated pharmacy computer decreased the amount of time pharmacists spent performing 28 activities by an average of 1.03 minutes per activity but increased the amount of time spent on activities directly affected by the computer by an average of 0.1 minute per activity. PMID- 1610474 TI - Photosystem II 23 kDa polypeptide of oxygen-evolving complex is encoded by a multigene family in tobacco. PMID- 1610473 TI - Interaction of basal positive and negative transcription elements controls repression of the proximal rat prolactin promoter in nonpituitary cells. AB - The proximal rat prolactin (rPRL) promoter contains three cell-specific elements, designated footprints I, III, and IV, which restrict rPRL gene expression to anterior pituitary lactotroph cells. Footprint II (-130 to -120) binds a factor, which we have termed F2F, present in pituitary and nonpituitary cell types. Here we demonstrate that a key role of the footprint II site is to inhibit rPRL promoter activity in nonpituitary cells, specifically, by interfering with the basal activating function of a vicinal element. Gene transfer analysis revealed 20-fold activation of the rPRL promoter in nonpituitary cell types when footprint II was either deleted or specifically mutated. Similar activation of the intact rPRL promoter was obtained by in vivo F2F titration studies. In GH4 rat pituitary cells, the footprint II inhibitory activity was masked by the redundant, positively acting cell-specific elements and was inhibitory only if the two upstream sites, footprints III and IV, were deleted. Deletion of the -112 to -80 region in the footprint II site-specific mutant background resulted in complete loss of rPRL promoter activity in both pituitary and nonpituitary cell types, mapping a basal activating element that is operative irrespective of cell type to this region. While the basal activating element imparted an activating function in a heterologous promoter assay, the footprint II sequence did not display any inherent repressor function and actually induced several minimal heterologous promoters. However, the inhibitory activity of the footprint II site was detected only if it was in context with the basal activating element. These data underscore the importance of ubiquitous activating and inhibitory factors in establishing cell-specific gene expression and further emphasize the complexity of the molecular mechanisms which restrict gene expression to specific cell types. We provide a novel paradigm to study rPRL promoter function and hormone responsiveness independently of lactotroph cell-specific requirements. PMID- 1610475 TI - How many ryanodine binding sites are involved in caffeine induced calcium release from sarcoplasmic reticulum terminal cysternae vesicles? AB - The inhibition by ryanodine of caffeine induced calcium release from actively loaded heavy sarcoplasmic vesicles has been studied in order to analyse the relation between the occupancy of the vesicular calcium release channels by ryanodine and channel function. Ryanodine binding was monitored with [3H]ryanodine under ionic conditions favouring the establishment of binding equilibrium. Binding follows 1:1 stoichiometry yielding dissociations constants between 7-12 nM and 12-15 pmol ryanodine/mg vesicular protein as maximum number of ryanodine binding sites. When ryanodine labeling was monitored by measuring the decline of the amplitude of caffeine induced calcium release 50% inhibition occurred at a free ryanodine concentration of 1 nM. At this concentration less than 10% of the available ryanodine binding sites are occupied. Caffeine induced calcium release is completely abolished when 3 pmol ryanodine/mg have reacted. A corresponding divergence between ryanodine binding and its effect on caffeine induced calcium release was observed when the initial rate of ryanodine binding was measured either by labeling the vesicles with [3H]ryanodine or by following the decline with time of caffeine induced calcium release. Caffeine induced calcium release declines four times faster than the fraction of unoccupied ryanodine binding sites, k = 4.3 x 10(4) M-1 s-1 versus 1.2 x 10(4) M-1 s-1. The observed interrelation between the occupation of ryanodine binding sites and its effect on caffeine induced calcium release indicates that the caffeine sensitive calcium channel functions as an assembly of at least 4 ryanodine binding sites whereby the occupation of one site suffices to abolish calcium release. The stoichiometric composition appears to be not fixed but might change according to the size of the fraction of ryanodine receptors exhibiting caffeine sensitivity. The reported data were evaluated according to the algorithm derived by H. Asai and M. F. Morales, J. Biol. Chem. 4, 830-838 (1965) for the activity of a macromolecule and the extent of an inhibiting reaction. PMID- 1610476 TI - [Embryotoxic interactions between a hydrolysis product of thalidomide and the surfactant Tween 20 in mice]. AB - N,N-phthaloyl-L-glutamic acid (NPLG), a hydrolysis product of thalidomide, and the surfactant Tween 20 were co-administered intraperitoneally to pregnant NMRI mice on days 9 and 8 2/3 p.c. at doses where the hydrolysis product as well as the surfactant alone induce minimal embryotoxicity. The combined substances (350 mg/kg NPLG + 1.0 ml/kg Tween 20) caused a potentiative teratogenic and an additive embryolethal response. Enhancement of the amount of Tween 20 in the combinations to 2.5 ml/kg led to the same potentiative teratogenic and, in addition, potentiative embryolethal response. Distribution studies using 14C-NPLG showed a strongly increased NPLG content in the maternal plasma under the influence of 2.5 ml/kg Tween 20 but not after co-administration with 1.0 ml/kg Tween 20. The malformations obtained were of the same type in all groups and mostly located in the vertebrae and ribs. These axial and paraxial defects were frequently more severe and included more affected elements after application of the combined than of the single substances. Extension of our experiments with the combined substances to treatment days 8 1/2 and 9 1/2 p.c. revealed that the first affected segment shifts in caudal direction depending on an increasing embryonal age at treatment. Limb malformations occurred at a low frequency; most of them were of the same type as described in cases of human thalidomide embryopathy. PMID- 1610478 TI - Modulation of the activities of membrane enzymes by cereal grain resorcinolic lipids. AB - Resorcinolic lipids, amphiphilic compounds from cereal grains show strong effects upon the activity of membrane enzymes. The concentrations for 50% inhibition of erythrocyte membrane acetylcholinesterase were in the range of 18-90 microM and were dependent on the length of the aliphatic side chain of the homologue and on the modification of hydroxyl groups in the benzene ring. Sulfonation of OH groups resulted in a drastic decrease of the inhibitory potency. The effect of resorcinolic lipids on the activity of Ca2+(calmodulin)-ATPase was the opposite. Up to concentrations of 50 microM alk(en)ylresorcinols stimulated the activity of this enzyme and only slight inhibition (approx. 30%) was observed above 100 microM. The results suggest that the effect of resorcinolic lipids might depend on their ability to alter the bilayer properties. Most probably these compounds decrease the mobility of membrane phospholipid molecules. PMID- 1610477 TI - [Biogenesis of Pseudomonas siderophores: the proof of analogous structures of a pyoverdin-desferriferribactin pair (1)]. AB - When grown in an iron-deficient medium Pseudomonas aptata produces both a desferri-ferribactin and a pyoverdin. The identical sequence of the peptide chain confirms the hypothesis that desferri-ferribactins are the biogenetic precursors of pyoverdins. PMID- 1610479 TI - Molecular dynamic simulations of the intercalation of benzothiopyranoindazole anticancer analogs with DNA models. AB - Fixed valence geometry intermolecular energy scans were carried out for a series of eight substituted anti-cancer benzothiopyranoindazoles (BTPI) interacting with (G-C) duplex models for DNA. The apparent intercalation energy minima identified in these scans were subsequently used as starting points in full-cartesian molecular dynamics relaxation simulations for 14 BTPIs. Intercalation in the major groove is preferred when both the ligand and DNA model possess formal charges. Otherwise, insertion of the ligand is modestly preferred from the minor groove. There are multiple minimum energy intercalation complexes within 5 kcal/mol of a global minimum for most analogs studied. The intercalation complex was investigated as a function of the molecular dielectric constant, epsilon, and the length of the (G-C) duplex segment. A wide range of epsilon values (3.5-50) can be employed without changing the relative order of stability of intercalation complexes. However, the absolute intercalation energy is quite sensitive to the selection of epsilon. (G-C)6 duplexes appear to be of adequate length to determine reliable estimates of the relative intercalation energetics. PMID- 1610480 TI - QSAR analysis of a set of benzothiopyranoindazole anti-cancer analogs based upon their DNA intercalation properties as determined by molecular dynamics simulation. AB - The global low-energy intercalation thermodynamic properties for a set of 14 benzothiopyranoindazole (BTPI) analogs, determined by molecular dynamics (MD) simulation, were used as descriptors in a quantitative structure-activity relationship (QSAR) analysis to describe their observed anti-cancer activities. The calculated free-space binding (intercalation) energies by themselves, or in combination with ligand lipophilicity, do not yield significant QSARs. However, the free-space binding energy combined with the aqueous desolvation energy of the intercalation complex leads to a highly significant QSAR. The optimum QSAR corresponds to both the ligand and DNA model being charged, and a molecular dielectric of 40 used in the force field. The desolvation energy is computed using a hydration-shell model. The QSAR suggests that anti-cancer activity can be enhanced by increasing the intercalating free-space binding energy and/or decreasing the loss in the favorable hydration energies of both the ligand and DNA when intercalation occurs. PMID- 1610481 TI - Synthesis and antitumor properties of new 4-methyl-substituted- pyrido[4,3 b]indoles (gamma-carbolines). AB - A new class of antineoplastic agents, 4-methyl-pyrido[4,3-b]indoles (5) and the related 4-hydroxymethyl derivatives (7), has been synthesized by a new pathway. Key transformations include regiospecific chlorination at the C(4)-position of 3 nitro-4-hydroxy-5-methyl-pyridin-2-(1H)-one (11) and photochemical cyclization of the intermediate triazolopyridones (15). This new synthesis was developed since an attempt to prepare 4-hydrazino-5-ethoxymethyl-pyridin-2-(1H)-one (10b) by the method previously used to obtain 4-hydrazino-5-methyl-pyridin-2-(1H)-one (10a) failed. The biological results obtained in different in vitro and in vivo models indicate that the substitution of the 4-CH3 by a 4-CH2OH group leads to a decrease of the antitumor properties. PMID- 1610482 TI - Towards rational design of antisense DNA: molecular modelling of phosphorothioate DNA analogues. AB - In order to assess the effects of substitution of one of the non-bridging oxygens in the phosphodiester group with sulfur, molecular dynamics calculations were performed on duplex oligodeoxynucleotides having a complete helical turn, [d(CpGpCpGpApApTpTpCpGpCpG)]2. The calculations were carried out with the unmodified duplex, as well as with duplexes having one phosphorothioate strand with uniform phosphorus stereochemistry (SP or RP). The electrostatic and structural (equilibrium molecular dimensions as well as force constants) parameters of the phosphorothioate group for molecular mechanics and dynamics calculations were derived from ab initio quantum mechanics optimizations of conformers of O,O'-dimethyl phosphorothioate. Molecular dynamics simulations (30 ps) were carried out using the AMBER force field, with explicit inclusion of all hydrogen atoms, counterions, and water. The simulations indicate a significant decrease of stability of the model containing the homochiral RP-phosphorothioate strand, whereas the model containing the homochiral SP-phosphorothioate strand has practically the same energy as the unmodified oligodeoxynucleotide duplex. The energy difference determined indicates some preference for the use of stereochemically pure SP-phosphorothioates as antisense gene inhibitors. Moreover, the significance of these results in connection with use of phosphorodithioates is discussed. PMID- 1610483 TI - Dimethanesulphonate esters in receptor mapping studies. 2. Antitumour activities of alkyl and alkoxy dimethanesulphonates substituted on a benzene nucleus. AB - The antitumour activities of 15 novel aromatic dimethanesulphonate esters were studied. Several alkyl and alkoxy compounds have shown good antitumour activity whilst similar isomers have proved ineffective as antitumour agents. These differences in activity have been correlated with the length of the sidechain substituents and their relative flexibilities. PMID- 1610484 TI - Nitrotriazoles bearing sulfur-substituted side chains: preparation and characterization as hypoxic cell radiosensitizers. AB - A series of 3-nitro-1,2,4-triazole (NTA) derivatives with -(CH2)mC(= Y)NH(CH2)nZCH3(Y, Z = O or S; m = 1 or 2; n = 2 or 3) group in the side chain at the N-1 position of NTA and their fluorinated analogs were synthesized. Their physicochemical properties and radiosensitizing activities in vitro and in vivo were investigated with respect, particularly, to the effects of sulfur substitution on the side chain of triazoles. The sulfur substitution of the oxygen atom in the side chain of NTA derivatives increased the partition coefficient (P value), but had little effect on the one-electron reduction potential. The derivatives bearing a thioether group in the side chain were more effective in vitro on hypoxic EMT6/KU cells, but were less effective in vivo on SCCVII tumor than their oxygen analogs. The thioamide compounds showed almost the same or slightly higher sensitizing activities in vitro compared with their oxygen analogs. PMID- 1610485 TI - Evidence for hypothalamo-growth hormone dysfunction in panic disorder: profile of growth hormone (GH) responses to clonidine, yohimbine, caffeine, glucose, GRF and TRH in panic disorder patients versus healthy volunteers. AB - Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha 2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear. To further delineate the status of hypothalamic-GH function in panic disorder, we review the literature and present original data on the GH responses to a number of different chemical and neuroendocrine challenge paradigms. Although stress-mediated increases in GH are thought to be a common correlate of stress in humans, our findings indicate that panic disorder patients have significantly blunted GH responses to clonidine, yohimbine, growth-hormone releasing factor, and caffeine compared to normal control subjects. A similar trend was noted in the delayed rise in GH after glucose challenge. There was no difference in the rate of abnormal GH responses to thyrotropin-releasing hormone in panic disorder compared to normal control subjects. No drug or neuroendocrine challenge, even if associated with marked increases in anxiety, produced a significantly enhanced GH response compared to normal control subjects. These findings provide support for a hyporesponsive hypothalamic-GH system in panic disorder. These observations, combined with preliminary observations from our clinic of short stature in several cases of prepubescent children with anxiety disorders, also underscore the need for assessing early growth patterns in individuals with panic disorder. Strategies for investigating the site(s) of possible neurotransmitter or hypothalamic-GH-somatomedin dysfunction are discussed. PMID- 1610486 TI - Dopamine and the neural circuitry of primate prefrontal cortex: implications for schizophrenia research. AB - Dopaminergic systems have been implicated in the pathophysiology of schizophrenia; the prefrontal cortex may be a site of dysfunction in this disorder. Until recently, however, relatively little was known about the organization of dopaminergic afferents, or the relationship of those axons to other elements of neural circuitry in the expanded and highly differentiated prefrontal cortex of primates. In this paper we review recent studies demonstrating that monkey prefrontal cortex is innervated by dopaminergic axons in a highly specific regional and laminar fashion. These findings are considered in the context of the organization of other neural systems in monkey prefrontal cortex and with regard to the extent to which they represent the organization of human prefrontal cortex. The resulting model of prefrontal cortical circuitry is then discussed in terms of the ways in which that circuitry might be disrupted in schizophrenia. PMID- 1610487 TI - New vistas in neuropeptide research in neuropsychiatry: focus on corticotropin releasing factor. AB - Advances in neuropeptide neurobiology in the last decade are illustrated by studies of corticotropin-releasing factor (CRF), the 41 amino acid-containing peptide that controls the anterior pituitary secretion of adrenocorticotropin and other pro-opiomelanocortin products. Corticotropin-releasing factor is synthesized in both hypothalamic and extrahypothalamic perikarya in a large prohormone form, (186 amino acids), then it is processed and transported to nerve terminals where it is released in its active form by a calcium-dependent mechanism. Corticotropin-releasing factor biosynthesis can now be measured by in situ hybridization because of the elucidation of the CRF gene sequence. Once released, CRF acts on high-affinity CRF receptors, and signal transduction is mediated by activation of adenylate cyclase in certain brain areas, and perhaps by phosphoinositide hydrolysis. In other brain areas CRF is inactivated by peptidases that degrade the hormone, though these are not well characterized. A CRF binding protein has been identified in plasma, and perhaps in brain. Considerable evidence exists from cerebrospinal fluid studies, postmortem tissue receptor measurements, and CRF stimulation test studies to support the hypothesis that CRF is hypersecreted in depression, resulting in both pituitary-adrenal axis hyperactivity and certain signs and symptoms of depression, e.g., decreased libido, insomnia, and decreased appetite. There is also evidence for an involvement of CRF in the pathophysiology of anxiety disorders and in the mechanism of action of benzodiazepines. The development of selective CRF-receptor antagonists will permit direct testing of the hypothesis that CRF hypersecretion is responsible for certain of the cardinal features of affective and anxiety disorders. PMID- 1610488 TI - Biological correlates of clinical heterogeneity in primary dementia. AB - While there is considerable variation in the clinical expression of Alzheimer's disease (AD), the determinants of this clinical heterogeneity remain unclear. Platelet membrane fluidity (PMF) identifies a subgroup of patients with AD with distinct clinical features that appear to be genetically determined. Results from an integrated series of studies suggest a cellular substrate for the increase in PMF associated with this clinical subgroup, and a model for the participation of the PMF locus in the pathophysiology of AD is proposed. In addition to this approach, studies of the neuropathologic and neurochemical determinants of major depression and psychosis in the context of primary dementia are presented. The results may explain the different prognoses associated with these behavioral syndromes in patients with AD, as well as the symptoms of the syndromes themselves. PMID- 1610490 TI - A study of interferon-gamma and interleukin-2 production in premature neonates and neonates with intrauterine growth retardation. AB - Mononuclear cells from aborted fetuses, preterm infants, intrauterine growth retardation (IUGR) fetuses, and mature infants were stimulated with OK432 and PHA to study their effect on the production of interferon gamma (IFN-gamma) and interleukin-2 (IL-2), respectively. IFN-gamma production was reduced in the mature delivery group, while its production in preterm delivery and IUGR groups was markedly reduced compared to those in adults and the mature delivery group. Reduced IFN-gamma production in preterm delivery and IUGR groups was attributable neither to a decrease in T-cells nor to enhanced sensitivity of T-cells to prostaglandins. Unlike IFN-gamma production, IL-2 production in preterm delivery groups was higher than that in adults; its production in the IUGR group was comparable to that in adults. In addition, both IFN-gamma and IL-2 production in premature delivery cases was enhanced when these cases were exposed to the stress of infection. PMID- 1610489 TI - Immune complexes that bind to ELISA plates not coated with antigen in mice infected with lactate dehydrogenase-elevating virus: relationship to IgG2a- and IgG2b-specific polyclonal activation of B cells. AB - We have further investigated the nature of IgG-containing complexes of 150-300 kD that rapidly appear in the circulation of mice of various strains after infection with lactate dehydrogenase-elevating virus (LDV) and are recognized and quantitated by their binding in the presence of 0.05% Tween 20 to certain enzyme linked immunosorbent assay (ELISA) plates with high protein affinity that have not been coated with protein antigen (5). These binding complexes have been found to contain primarily IgG2a or, in some mice, IgG2b. Their isotype specificity and time course of formation correlated with those of the polyclonal production of immunoglobulins in these mice, as measured by increases in total IgG2a or IgG2b in the circulation. In contrast, anti-LDV antibodies exhibited much broader isotype specificities in all mouse strains investigated. Depletion of BALB/c mice of CD4+T cells or lack of T cells in nude Swiss mice only partly reduced the polyclonal activation of B cells and the formation of ELISA plate-binding complexes, whereas anti-LDV antibody formation was completely blocked. Only a small proportion of the total IgG2a or IgG2b formed as a result of the LDV induced polyclonal activation of B cells was recovered in plate-binding complexes, which sedimented in sucrose density gradients between 150 and 300 kD. Diverse monoclonal antibodies of different IgG isotopes did not bind to the plates at concentrations at which LDV-induced immune complexes exhibited binding activity. We suggest that the LDV-induced immune complexes do not contain anti LDV antibodies, but are complexes of auto-antibodies and self-antigen(s). However, additional features must be responsible for the high affinity of these complexes for ELISA plates since various immune complexes formed in vitro failed to bind to the plates, and binding activity of the immune complexes formed in LDV infected mice could not be regenerated in vitro once the complexes had been dissociated by a low pH treatment. PMID- 1610491 TI - Leukocyte distribution in the pseudopregnant mouse uterus. AB - Pseudopregnancy, induced by mating females with vasectomized males, is a frequently used model for studying pregnancy-like uterine changes in the absence of an embryo. Leukocytes make a significant contribution to uterine cellularity during pregnancy. The present study was designed to determine whether changes in numbers and distribution of leukocytes in the uterus during pseudopregnancy and following intraluminal injection of a deciduogenic stimulus parallel changes observed during the first eight days of pregnancy. Common leukocyte antigen positive (CLA+) cells, macrophages (F4/80+ cells), and granulocytes were assessed between days 1 and 8 of pseudopregnancy using qualitative and quantitative immunohistochemistry. High numbers of CLA+ leukocytes were present on days 1 and 2. Those were comprised primarily by macrophages, polymorphonuclear leukocytes, and eosinophils. High concentrations of leukocytes were detected in the endometrium, and some granulocytes were observed migrating through the luminal epithelium. Leukocytes, principally macrophages, were reduced in number and were distributed throughout the endometrium on days 3 and 4. Introduction of oil to the uterine lumen on day 4 stimulated primary decidualization. Decidual cells were CLA- and F4/80-, and, as decidualization proceeded, CLA+ and F4/80+ cells decreased in number in the anti-mesometrial uterus and were detected primarily in the deep endometrium. Later, a secondary decidualization zone developed in the mesometrial aspect of the uterus. Unlike the initial decidual reaction, which was relatively free of leukocytes, the secondary decidual zone contained very high numbers of CLA+ and F4/80+ cells. The uninjected uterine horn remained relatively unchanged from days 3 through 8.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610493 TI - Reproductive immunology: a personal view. PMID- 1610492 TI - Evaluation of a monoclonal antibody, BC-1, which identifies an antigen expressed on the surface membrane of human extravillous trophoblast. AB - This paper describes a new Mab BC-1 which is directed at a cell surface antigen expressed by extravillous cytotrophoblast and not by villous cytotrophoblast, so it is useful for distinguishing between the two populations. The antigen recognised by BC-1 is trypsin-resistant, which allows it to be used for flow cytometric analysis of living trophoblast isolated by enzymic disaggregation. However, BC-1 is not trophoblast-specific but cross-reacts with some other tissues, in particular endothelial cells and peripheral blood monocytes. The nature of this antigen has not been established. PMID- 1610494 TI - Preliminary communication: possible role of reactive nitrogen intermediates in leucocyte-mediated sperm dysfunction. AB - This preliminary study was designed to examine whether nitric oxide, a reactive nitrogen intermediate produced by leukocyte metabolism of L-arginine, could reduce sperm motility. Increasing doses (10(-6)-10(-4) M) of the nitric oxide generating drug, sodium nitroprusside (SNP) were added to motile sperm preparations and incubated over 20 hr. Quantitative sperm motility measurements were made using a computer-assisted motility analyzer in each treated sample and controls over this time period. The percentage of motile sperm, progressive motility, and concentration of motile cells were all significantly reduced with all doses of SNP. This effect was not observed in preparations treated with oxyhaemoglobin (HbO2). Mean path velocity was unaltered. Sperm viability in SNP treated sperm did not differ significantly from that of control sperm over the same time period. We conclude that further experiments are required to determine whether the production of nitric oxide/reactive nitrogen intermediates in vivo by activated leukocytes could be a contributory factor in the development of immunologic infertility. PMID- 1610495 TI - Fetal renal defects: associated malformations and chromosomal defects. AB - During a 6-year period (1985-1990) blood karyotyping was performed in 682 fetuses with renal defects. There were: 276 fetuses with mild hydronephrosis; 206 with moderate/severe hydronephrosis; 173 with multicystic dysplasia, and 27 with renal agenesis. The overall incidence of chromosomal abnormalities was 12% (trisomies, n = 63; deletions, n = 9; triploidies, n = 5, and sex chromosome aneuploidies, n = 8). There were more than twice as many males than females, but the incidence of chromosomal defects in females was almost double (18%) than in males (10%). Furthermore, compared to the overall maternal age-related risk, the risk for fetal chromosomal abnormalities was three times higher when there was an isolated renal defect and thirty times higher when there were additional malformations. The risk of chromosomal abnormalities was similar for fetuses with unilateral or bilateral involvement, different types of renal defects, urethral or ureteric obstruction, and oligohydramnios or normal/reduced amniotic fluid volume. Nevertheless, the patterns of chromosomal abnormalities, and consequently that of associated malformations, were related to the different types of renal defects. PMID- 1610496 TI - Management of prenatally diagnosed tracheal obstruction: access to the airway in utero prior to delivery. AB - A fetus of 23-weeks gestation presented with polyhydramnios, and was found on sonography to have a large anterior cervical teratoma. At 26 weeks the mother went into premature labor and the membranes ruptured; at this time the uterus was of 32-weeks size secondary to polyhydramnios. A cesarean section was performed through a low transverse uterine incision, and the fetal head and shoulders were delivered with the cord intact. An endotracheal tube was placed, and the cord was then divided. The baby was taken to the neonatal intensive care unit for stabilization prior to planned resection, but suffered pharyngeal hemorrhage followed by endotracheal tube dislodgement several hours after birth, and expired. Despite an unfortunate outcome, this case illustrates the feasibility and potential value of in utero airway access in cases of prenatally diagnosed tracheal obstruction. PMID- 1610497 TI - A probable case of superfecundation. AB - Discordant twins are of obstetrical concern because of high morbidity and mortality of either the smaller or the larger twin, or both. The discordance becomes apparent usually in the second trimester. We report a case of discordant twins diagnosed in the 10th week of gestation, which was concluded to be a case of superfecundation. The discordancy was persistent up to the 35th week of gestation, when 2 baby boys were born by cesarean section because of preeclampsia. The postnatal courses of the babies were uneventful. PMID- 1610498 TI - Fetal and maternal erythropoietin levels in normal pregnancy. AB - In a cross-sectional study of 120 pregnancies undergoing cordocentesis for prenatal diagnosis (n = 90) or elective caesarean section (n = 30), the umbilical cord and maternal venous plasma erythropoietin (Epo) concentrations were measured. Fetal Epo levels increased from a mean of 4 mU/ml at 16 weeks to 13 mU/ml at 40 weeks' gestation. There were no significant associations between fetal plasma Epo concentration and fetal blood gases, haemoglobin concentration, oxygen content or erythroblast count. The maternal plasma Epo concentration (mean = 14 mU/ml, range 1-77 mU/ml) did not change with gestation but was significantly higher than levels in non-pregnant females (mean = 6.6 mU/ml, range 1-25 mU/ml). PMID- 1610499 TI - Tissue heating effect of pulsed Doppler ultrasound in the live fetal lamb brain. AB - A series of experiments in fetal lambs investigated the heating effects of pulsed Doppler ultrasound on fetal brain tissue. In dead lamb brain, tissue heating was observed at the skull bone-to-brain interface. Minimal or no temperature rise was found in the live lamb, suggesting that the intact circulation conducts away any potential heating. The choice of animal model and the state of the circulation influence the results obtained. This will of course have implications for clinical practice. PMID- 1610500 TI - Obstetric evolution of pregnancies obtained from donated oocytes. AB - Of 44 pregnancies obtained at the Tenon Maternity Hospital by in vitro fertilization (IVF) using donated oocytes, 25 have already been completed by spontaneous delivery or cesarean section: 22 (88%) single; 2 (8%) twins, and 1 (4%) triple. The most frequently seen complications of pregnancy were hypertension (16%) and preterm labor in the last 3 months (12%). However, as compared to a control group of 275 pregnancies resulting from classical IVF, the only difference was a very high percentage of cesarean sections (72%). No fetal deaths or neonatal malformations were reported. PMID- 1610501 TI - Intravascular pancuronium bromide infusion for prenatal diagnosis of twin-twin transfusion syndrome. AB - The diagnosis of twin-twin transfusion syndrome remains a problem. Intravascular infusion of pancuronium bromide, a nondepolarizing neuromuscular blocking agent, for the smaller of a set of twins demonstrated paralysis of both twins in one case. However, in a second case, paralysis was shown only in the smaller twin who demonstrated no transplacental vascular communications postnatally. We suggest that infusion of pancuronium bromide, 'pancuronium test', is a simple and safe method for confirming transplacental communications and aids in the diagnosis of twin-twin transfusion syndrome. PMID- 1610502 TI - Selective embryo reduction of an interstitial heterotopic gestation. AB - A case of combined interstitial and intrauterine pregnancy is described. The sonographic finding of a thick myometrial bridge separating a twin pregnancy may be unique to heterotopic cornual pregnancies and is illustrated. The method of selective embryo reduction with potassium chloride to terminate the interstitial pregnancy without damage to the intrauterine pregnancy is also described. The intrauterine pregnancy continued successfully to term. PMID- 1610503 TI - Hypoplasia of the lung and heart in fetal rats with diaphragmatic hernia. AB - We studied 11 fetal rats with normal heart and diaphragmatic hernia induced by administration of bis-diamine (200 mg) on the 9th and 10th day of pregnancy. After rapid whole-body freezing on the 21st day, the fetuses were studied by means of serial cross-sectional photographs of the frozen thorax. In the fetuses with hernia, the left half of the diaphragm was completely absent, and the liver and stomach were in the left hemithorax. The lung and heart were hypoplastic in fetal diaphragmatic hernia. Cardiac volume reduction involved all four chambers and was more prominent in the left atrium and ventricles. The great vessels were also smaller. PMID- 1610504 TI - [Outbreak of paratyphoid fever among Peruvian naval personnel]. AB - A retrospective epidemiological study was conducted in connection with an outbreak of paratyphoid fever at a Peruvian naval installation in Callao. The study sought to determine the magnitude of the outbreak, the source of infection, the attack rates, the persistence of bacilli excretion, and the clinical picture of the disease. The source of Salmonella paratyphi B infection had been a meal of chicken and rice served to around 400 members of the naval police. Over a period of three weeks, 21 persons were hospitalized and 52 received outpatient treatment at the naval hospital. In addition, through a questionnaire it was revealed that 86 unreported cases of diarrhea related to the outbreak had occurred. The most common clinical manifestations were fever, headache, weakness, anorexia, abdominal pain, and diarrhea. The general attack rate was 39.8%. In a follow-up survey carried out 37 days after exposure, fecal cultures indicated that 8.5% of the persons affected continued to excrete the microorganism. The high rates of attack and transmission of S. paratyphi B in this outbreak point up the considerable pathogenicity and virulence of some strains of the microorganism and their impact on public health. It is suggested that preventive measures be taken at naval and other similar installations, including the education of workers who handle and prepare food, in order to ensure proper hygiene. PMID- 1610505 TI - Dimensions of affective experience in three age groups. AB - The dimensions by which adults of differing ages experience emotion were studied by self-administering questionnaires administered to older adults (n = 828) recruited from Elderhostel programs, middle-aged (ages 30-59) children of Elderhostel attenders (n = 231), and young adult (ages 18-29) subjects recruited from college classes or through Elderhostel participants (n = 207). Elders were higher in emotional control, mood stability, and emotional maturity through moderation and leveling of positive affect and lower in surgency, psychophysiological responsiveness, and sensation seeking. These findings are consistent with the hypothesized increase in self-regulatory capacity with age. These cross-sectional differences cannot, however, be distinguished from cohort related explanations; they require considerable replication across different types of subjects and further characterization of the dimensions in terms of their functions for self-regulation. PMID- 1610506 TI - Correlates of memory decline: a 4-year longitudinal study of older adults with memory complaints. AB - Change in memory performance and its correspondence to change in speed of performance and self-reported memory functioning were investigated longitudinally in 30 older adults with memory complaints. Subjects were assessed by self-report questionnaires and cognitive tests 3 times, at near 2-year intervals. A significant decline in word-recall scores was found, which was accompanied at the group level by significant self-reported decline in everyday memory functioning and nonsignificant decline in Wechsler Adult Intelligence Scale Digit Symbol scores (alpha = .05). The oldest subjects showed the most substantial declines in memory performance. At the individual level, however, memory change did not significantly correlate with either change in self-reports or change in Digit Symbol scores. Although these results do not support a cognitive slowing model of decline at the intraindividual level, they do have implications for intervention of age-related memory decline. PMID- 1610507 TI - Age differences in adults' control beliefs related to life goals and concerns. AB - Control beliefs play an important role in how people direct their own development during their life span. However, research into age differences in control beliefs has produced inconsistent results. In this study, 381 subjects (19 to 71 years old) completed a questionnaire in which they were asked to write down their goals and concerns. They were then asked to rate each on a 4-point bipolar rating scale measuring internality-externality. The results showed that subjects' control beliefs became more external with age. However, part of the increase in externality was found to be caused by increasing interest in domains that are generally considered uncontrollable. Subjects' beliefs about health-, self-, offspring-, and property-related goals became more external with age, unlike goals concerning future education, occupation, family, and travel. PMID- 1610508 TI - Confrontation naming in Alzheimer's patients: relation to disease severity. AB - Reports of Alzheimer's disease patients in whom naming performance is disproportionate to other cognitive performances raise questions about the stage model, or dementia-severity level, for predicting naming performance. Thus, dementia severity as defined by Global Deterioration Scale ratings, Mini-Mental State Examination scores, and combinations of them was evaluated as a predictor of naming performance in 102 Alzheimer's patients and was found to account for approximately 1/3 of performance variability. Additional contributions from age at onset, duration, family history, and gender were negligible. Therefore, naming ability can be argued to have a subcomponent that is not subsumed by overall cognitive ability. PMID- 1610509 TI - Health screening and random recruitment for cognitive aging research. AB - A survey of 197 cognitive aging studies revealed infrequent use of structured health assessments and random recruitment. In this study, a health screening questionnarie developed to identify subjects with medical problems that might impair cognition was administered to 315 adults aged 60 and older who were recruited by random digit dialing. On the basis of self-reported medical problems, 35% of the subjects were excluded. Those excluded were older (p less than .001) and tended to be male but did not differ in education from those who passed the screening. Subjects who passed the screening and decided to participate in a neuropsychological research project were younger (p less than .001), better educated (p less than .001), and more likely to be male (p less than .001) than nonparticipants. These findings suggest that careful assessment, selection, and description of subjects is needed to aid interpretation of cognitive aging research. Further attention to health status is needed to aid interpretation of cognitive aging research. Although random recruitment of the elderly is feasible, obtaining representative samples may require stratification on demographic variables. PMID- 1610510 TI - Factorial structure of two health belief measures among older adults. AB - Confirmatory factor analysis of Wallston's Multidimensional Health Locus of Control Scale and Krantz's Health Opinion Survey was conducted using 197 nondiabetic and 171 diabetic older adults. Qualified support was found for the 3 factor structure of the Wallston measure when applied to older adults. The Krantz model provided a less-than-adequate representation of the older sample's data. When the items from these 2 measures were combined, a 4-factor structure was found. Multisample simultaneous factor analyses using LISREL revealed that the factor structures of the Wallston and the Krantz measures fit the diabetic and the nondiabetic samples fairly equivalently. Despite the similarities in factor structures, diabetic individuals reported greater belief in powerful others and less desire for behavioral involvement in the health-care process than did nondiabetics. PMID- 1610511 TI - When Greta Garbo is easier to remember than Stefan Edberg: influences of prior knowledge on recognition memory in Alzheimer's disease. AB - This study investigated the effects of prior knowledge on recognition memory in patients with a mild Alzheimer's disease. Normal older adults and mildly demented patients were presented with dated and contemporary famous faces with name tags and were asked to generate unique statements about each person. Results indicated that both groups generated more statements about the dated than about the contemporary figures. Most important, both groups performed better with the dated than with the contemporary faces in an unexpected episodic face recognition task. This pattern of results suggests that both groups (a) possess more knowledge of dated than of contemporary famous individuals and (b) are able to utilize prior knowledge to enhance episodic remembering. Viewing these results in light of other recent work, it is concluded that differences between normal old and mildly demented individuals in the ability to utilize cognitive support for remembering may be differences in degree. PMID- 1610512 TI - Adults' conceptions of intelligence across the adult life span. AB - To examine whether young, middle-aged, and older adults view the concept of intelligent person as similar or different during adulthood, 140 adults of various ages rated how likely it would be for individuals of average and exceptional intelligence at 30, 50, and 70 years of age to be engaged in behaviors previously identified by adults as characterizing adult intelligence. Adults perceived more similarity between exceptionally intelligent prototypes of closer ages (i.e., 30 and 50 and 50 and 70). Intelligence was perceived to consist of interest and ability to deal with novelty, everyday competence, and verbal competence--dimensions that were perceived to be differentially important for different-aged prototypes and by individuals of different ages. Participants' conceptions also included the idea that intelligence is malleable and that abilities differentially increase or decrease across the life span. PMID- 1610513 TI - Adult age differences in the rate of learning serial patterns: evidence from direct and indirect tests. AB - Subjects performed a serial reaction time task (adopted from Nissen & Bullemer, 1987) that contained a repeating pattern of spatial locations. In Experiment 1, following 20 repetitions of a 10- or 16-element pattern, reaction time was equally disrupted for both younger and older people when the sequence became random. In Experiment 2, the response times for subjects encountering the 10 element pattern were compared with those of subjects encountering a random sequence. These response time functions diverged at the same point in training for the 2 age groups. Thus, on this indirect measure of response time facilitation, both experiments revealed age similarity in the rate of pattern learning. In contrast, on a subsequent direct test of pattern learning that required prediction, the younger people earned a higher percentage correct score than the older in both experiments. Age-related dissociations between direct and indirect measures of learning and comparisons with memory-impaired populations are discussed. PMID- 1610514 TI - Medication adherence behaviors in older adults: effects of external cognitive supports. AB - Medication adherence behaviors of 61 elderly adults were examined using a sensitive microelectronic monitoring device. To assess the effects of external cognitive supports on adherence, different subjects received (a) no intervention, (b) an organizational chart, (c) an over-the-counter medication organizer, or (d) both the chart and organizer. The young-old subjects showed a high rate of adherence (94%) and were not improved by the addition of the interventions. Old old subjects had a lower rate of adherence (85%) than young-olds. Omission errors were the most frequent mistakes and were lower in the condition in which subjects received both chart and organizer. PMID- 1610515 TI - General slowing in semantic priming and word recognition. AB - Analyses of lexical decision studies revealed that (a) older (O) adults' mean semantic priming effect was 1.44 times that of younger (Y) adults, (b) regression lines describing the relations between older and younger adults' latencies in related (O = 1.54 Y-112 and unrelated conditions (O = 1.50 Y-93) were not significantly different, and (c) that there was a proportional relation between older and younger adults' priming effects (O = 1.48 Y-2). Analyses of word-naming studies yielded similar results. Analyses of delayed pronunciation data (Balota & Duchek, 1988) revealed that word recognition was 1.47 times slower in older adults, whereas older adults' output processes were only 1.26 times slower. Overall, analyses of whole latencies and durations of component processes provide converging evidence for a general slowing factor of approximately 1.5 for lexical information processing. PMID- 1610516 TI - Wisdom-related knowledge in a life review task: age differences and the role of professional specialization. AB - The study adopts life review as an avenue to access wisdom-related knowledge and examines the contribution of age and type of professional specialization to individual differences in wisdom-related knowledge. Women from 2 age groups/cohorts (young, M = 32 years; old, M = 71 years) and different professional specializations (human services vs. nonhuman services) were asked to think aloud about the life review of a fictitious woman who was either young or old. Verbal protocols were scored on 5 wisdom-related criteria: factual and procedural knowledge about life, life-span contextualism, relativism of values, recognition, and management of uncertainty. Three major findings emerged. First, human-services professionals outperformed the control group. Second, old adults performed as well as young adults. Third, for older adults wisdom-related performance was enhanced by the match between their own age and the age of the fictitious character. PMID- 1610517 TI - A cognitive-behavioral therapy for sleep-maintenance insomnia in older adults. AB - Older adults (3 men, 4 women, aged 55 to 68 years) with chronic sleep-maintenance insomnia were treated sequentially with relaxation therapy (RT) and then with a cognitive-behavioral therapy (CBT) specifically designed for alleviating sleep maintenance problems. Sleep diaries and an objective measure of sleep, the sleep assessment device, showed only modest improvements in measures of wake time after sleep onset, sleep efficiency, and night-to-night sleep variability following RT. However, significant improvements in these measures were observed following CBT and at a 3-month follow-up. These findings, considered in conjunction with previous reports, suggest that CBT specifically addresses factors that sustain sleep maintenance complaints. Additional trials of CBT with larger samples are warranted. PMID- 1610518 TI - Recollective experience, normal aging, and frontal dysfunction. AB - This study examined the nature of verbal recognition memory in young and old subjects. Following presentation of a word list, subjects undertook a yes-no recognition test and indicated whether their decision was based on explicit recollection or assessment of familiarity. Explicit recollection declined with age, and familiarity-based recognition increased. Furthermore, the extent to which older subjects relied on familiarity-based recognition correlated with neuropsychological indices of frontal lobe dysfunction. A further experiment indicated that the change from explicit recollection to familiarity-based responding was unrelated to changes in older subjects' confidence about their memory. The data indicate the central role of frontal dysfunction in understanding age-related memory loss. PMID- 1610519 TI - Implicit and explicit memory for novel visual objects in older and younger adults. AB - Two experiments examined effects of aging on implicit and explicit memory for novel visual objects. Implicit memory was assessed with an object decision task in which subjects indicated whether briefly exposed drawings represented structurally possible or impossible objects. Explicit memory was assessed with a yes-no recognition task. On the object decision task, old and young subjects both showed priming for previously studied possible objects and no priming for impossible objects; the magnitude of the priming effect did not differ as a function of age. By contrast, the elderly were impaired on the recognition task. Results suggest that the ability to form and retain structural descriptions of novel objects may be spared in older adults. PMID- 1610520 TI - Adult age differences in short-term memory and subsequent long-term memory for actions. AB - Short-term memory for actions was investigated for young adult and elderly adult subjects with the Brown-Peterson procedure at retention intervals of 0 and 15 s. The short-term memory trials were followed by the long-term recall of the prior to-be-remembered actions. The 15-s retention interval was filled either with no activity or with 1 of 3 different interfering activities. Verbal interference had little effect on short-term memory at either age level. Actions performed in the interval either by the subjects or by the experimenter produced significantly lower recall scores at each age level, with the decrement being more pronounced for the elderly than for the young subjects. The long-term memory results indicated that successful short-term recall enhanced later long-term recall, regardless of age level. PMID- 1610521 TI - Linear and nonlinear effects of aging on categorizing and naming faces. AB - Subjects aged 54-84 performed 5 separate tasks involving various aspects of face processing: structural decisions (1), familiarity decisions (2), semantic decisions (3), first-name decisions (4), and name retrieval (5). For the categorization tasks (1-4), the mean reaction times for the older subjects (over 65) were plotted against the corresponding means for the younger subjects (under 65). This produced a linear function (slope greater than 1, intercept less than 0), providing only partial support for a simple, multiplicative model of cognitive slowing with age. Reaction time distributions were also plotted for each of the 5 tasks (older vs. younger subjects). The resulting functions were almost perfectly linear, with the exception of name retrieval, which was exponential with respect to age. This was attributed to the increased probability of a tip-of-the-tongue state with age caused by insufficient activation at the level of the name information (the final state of face identification). PMID- 1610522 TI - Nightmare prevalence in the healthy elderly. AB - Fifty-one healthy elderly subjects (median age = 65) gave retrospective estimates of nightmare frequency in questionnaires and recorded the occurrence of nightmares in daily logs over a 2-week period. (a) Mean annual nightmare frequency as estimated from logs was only 65% as high among college student controls. (b) Elderly subjects were about 1/5 as likely as college students to report a problem with nightmares. (c) Frequency estimates on the basis of logs were over 10 times higher than retrospective estimates. PMID- 1610523 TI - Convective model of cross-flow microfiltration. AB - In membrane microfiltration of colloidal and cellular suspensions tangential feed ensures continuous operation. Neglecting diffusion (Pe much greater than 1) the purely convective approach predicts well observed dependences between technological parameters and solves the so called microfiltration paradox. PMID- 1610524 TI - Special issue in honour of Professor A. Scheludko on the occasion of his 70th birthday. PMID- 1610525 TI - Stability and permeability of amphiphile bilayers. AB - In this review the rupture and permeability of bilayers are considered on the basis of a mechanism of the formation of microscopic holes as fluctuations in the bilayers. The hole formation is treated as a nucleation process of a new phase in a two-dimensional system with short-range intermolecular forces. Free rupture and deliberate rupture (by alpha-particles) of foam bilayers (Newtonian black films) are discussed. A comparison is made between the rupture of foam and emulsion bilayers. Experimental methods for obtaining foam and emulsion bilayers from thin liquid films are considered. Methods for investigating the stability and permeability of foam bilayers, which are based on a microscopic model allowing the use of amphiphile solutions with very low concentrations, are described. Experimental dependences of the lifetime of bilayers, the probability of observing the foam bilayer in a foam film, the gas permeability of bilayers, etc. on the concentration of amphiphile molecules in the solution are reported. The influence of temperature and external impact (e.g. alpha-particle irradiation) have also been experimentally studied. A good agreement between theory and experiment is established, allowing determination of several characteristics of foam and emulsion bilayers obtained from ionics or non-ionics: the specific edge energy of bilayer holes, equilibrium surfactant concentration below which the bilayer is thermodynamically metastable, work for the formation of a nucleus hole, number of vacancies in the nucleus hole, coefficient of gas diffusion through the bilayer, etc. On the basis of the effect of temperature on the rupture of foam bilayers the binding energy of a surfactant molecule in the bilayer is determined. The adsorption isotherm of surfactant vacancies in the foam bilayer is obtained which shows a first-order phase transition. Some applications to scientific, technological and medical problems are considered. The foam bilayer is used as a model for investigating short-range forces in biological structures, the interaction between membranes and cell fusion. It is also shown that the foam bilayer is a suitable model for studying the alveolar surface and stability. On that basis a clinical diagnostic method is developed for assessment of the human foetal lung maturity. PMID- 1610526 TI - Structure of sodium perbromate monohydrate. AB - NaBrO4.H2O, Mr = 184.90, monoclinic, C2/c, a = 15.7575 (19), b = 5.7373 (15), c = 11.3390 (19) A, beta = 111.193 (10)degrees, V = 955.8 (3) A3, Z = 8, Dx = 2.570 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 85.2 cm-1, F(000) = 704, T = 296 K, R = 0.039 for 1137 unique reflections having I greater than sigma I. In this structure, there are two inequivalent Na ions, each coordinated by six O atoms. In each of the two types of distorted octahedra, there are three inequivalent Na- O distances; the average Na(1)--O and Na(2)--O distances are 2.379 (10) and 2.405 (23) A, respectively. The perbromate ion in this structure displays very nearly regular tetrahedral geometry, although it is subject to no symmetry constraints; the average observed Br--O distance is 1.601 (4) A, while the average observed O- Br--O angle is 109.5 (9)degrees. These values agree well with previously reported values. The perbromate ion, but neither of the sodium coordination polyhedra, shows rigid-body behavior. The average rigid-body corrected Br--O distance in the perbromate ion is 1.624 (3) A. Refinement of the two inequivalent H atoms permitted detailed analysis of the hydrogen bonding, which is slightly different from that reported for the isomorphic sodium perchlorate monohydrate. Dynamic disordering of the H atoms as detailed by magnetic resonance methods for sodium perchlorate monohydrate is not clearly indicated in our X-ray study of sodium perbromate monohydrate. PMID- 1610527 TI - Structures of zinc(II) with tetradentate N2S2 ligation. AB - trans-3,3'-(1,2-Cyclohexanediyldinitrilo)-bis(2-methylpropane++ +-2-thiolato )]zinc(II), [Zn(C14H28-N2S2)], Zn(2), Mr = 353.89, monoclinic, C2/c, a = 17.914 (4), b = 9.440 (1), c = 10.877 (2) A, beta = 110.19 (2)degrees, V = 1726 (1) A3, Z = 4, Dm = 1.35 (1), Dx = 1.360 Mg m-3, mu(Mo K alpha, lambda = 0.71073 A) = 0.17 mm-1, F(000) = 752, T = 298 (1) K, RF = 0.026, wRF = 0.037 for 1290 reflections. 3,3'-(1,2-Cyclohexa-1,4- dienediyldinitrilo)bis(2-methylpropane-2 thiolato)] zin c(II), [Zn(C14H24N2S2)], Zn(3), Mr = 349.86, monoclinic, P2(1)/c, a = 9.760 (2), b = 17.326 (3), c = 10.530 (2) A, beta 91.49 (2)degrees, V = 1780 (1) A3, Z = 4, Dm = 1.31 (1), Dx = 1.305 Mg m-3, mu(Mo K alpha, lambda = 0.71073 A) = 0.16 mm-1, F(000) = 736, T = 297 (1) K, RF = 0.050, wRF = 0.062 for 1723 reflections. The structures consist of discrete complexes with distorted tetrahedral ZnS2(thiolate)N2(amine) coordination geometries. Zn--S [2.2533 (6) A for Zn(2); 2.259 (1), 2.253 (1) A for Zn(3)] and Zn--N [2.101 (2) A for Zn(2); 2.088 (4), 2.128 (4) A for Zn(3)] distances are close to those reported for similar structures with bidentate N(amine)S(thiolate) ligands. The N,S chelate rings in both structures exhibit the envelope conformation with the tetrasubstituted C atoms comprising the flaps. In Zn(3), the central N,N chelate ring adopts the envelope conformation, while in Zn(2), the corresponding ring is gauche.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610528 TI - Structure of the sodium salt of 1,4,5,8-naphthalenetetracarboxylic acid 4,5 anhydride hydrate. AB - Sodium hydrogen 1,3-dioxo-1H,3H-naphtho[1,8-cd]pyran-6,7-dicarboxylate hydrate, Na[C14H5O7].H2O, Mr = 326.2, triclinic, P1, a = 9.520 (2), b = 9.549 (3), c = 7.860 (1) A, alpha = 105.88 (2), beta = 110.29 (1), gamma = 100.89 (2) degrees, V = 611.9 (3) A3, Z = 2, Dx = 1.77 g cm-3, lambda(Mo K alpha) = 0.71073 A, mu = 1.67 cm-1, F(000) = 332, T = 295 K, R = 0.042 for 1665 unique reflections having I greater than 3 sigma I. The organic portion of this structure demonstrates near C2 symmetry with a pseudo-twofold axis coincident with the central C-C naphthalene ring bond. The atoms of the naphthopyran three-ring system deviate by an average of 0.037 (19) A from the best least-squares plane through the three rings. Each of the carboxyl group planes is substantially inclined to the naphthopyran ring plane, the average dihedral angle measuring 62 (1) degree. The Na ion is coordinated by O atoms in a highly distorted octahedral geometry with a mean Na--O distance of 2.49 (12) A. A short hydrogen bond is formed between a carboxylic acid group and a carboxylate anion; the H...O(acceptor) distance is 1.35 (5) A and the O...O(acceptor) distance is 2.475 (3) A. The acid H-atom position is located asymmetrically with respect to the O atoms. The water H atoms are involved in unequal three-centered hydrogen bonds. The molecules are stacked such that the naphthopyran ring portion of the structure is nearly parallel to the ab cell face and the stacks are connected by the hydrogen bonds.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610529 TI - Structures of new DNA photocleaving agents: 3,6-bis(dimethylamino)-10- [6-(4 nitrobenzoyloxy)hexyl]acridinium chloride (I) and 9-([6-(4- nitrobenzoyloxy) hexyl]amino)acridinium chloride monohydrate (II). AB - (I) C30H35N4O4+.Cl-, Mr = 551.07, triclinic, P1, a = 10.512 (2), b = 11.203 (2), c = 14.469 (2) A, alpha = 111.49 (1), beta = 105.74 (1), gamma = 95.82 (1) degrees, V = 1487.4 (4) A3, Z = 2, Dm = 1.23 (by flotation), Dx = 1.231 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 14.68 cm-1, F(000) = 584, T = 296 K, R = 0.109 for 3100 unique reflections with I greater than 3 sigma(I). (II) C26H26N3O4+.Cl-.H2O, Mr = 497.98, triclinic, P1, a = 9.4810 (8), b = 14.495 (2), c = 9.255 (1) A, alpha = 95.48 (1), beta = 98.17 (1), gamma = 101.78 (1) degrees, V = 1222.3 (5) A3, Z = 2, Dm = 1.35 (by flotation), Dx = 1.353 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 17.34 cm-1, F(000) = 524, T = 296 K, R = 0.052 for 3589 unique reflections with I greater than 3 sigma(I). The diffraction work confirmed the molecular structures of the newly synthesized DNA photocleaving compounds, in which the p-nitrophenyl group is nearly coplanar with the acridine moiety in (I), whereas the two planar groups form a dihedral angle of 98.7 degrees in (II). The flexibility of the methylene chain and the substantial stacking ability of the aromatic groups observed may be essential for binding to DNA and reaction with the deoxyribose H atoms. PMID- 1610530 TI - Structure of trans-3,3-dichloro-4-(alpha-chlorobenzyl)-1-methyl-5-phenyl-2 pyrrolidi none. AB - C18H16Cl3NO, Mr = 368.69, triclinic, P1-, a = 10.360 (1), b = 10.397 (1), c = 10.810 (2) A, alpha = 60.84 (1), beta = 57.22 (1), gamma = 70.97 (1) degrees, V = 852 (1) A3, Z = 2, Dx = 1.437 Mg m-3, Mo K alpha radiation, lambda = 0.71073 A, mu = 0.54 mm-1, F(000) = 380, T = 293 (1) K, R = 0.0287 for 2330 observed reflections with I greater than 3 sigma (I). The five-membered ring has an envelope conformation and the 4-(alpha-chlorobenzyl) and 5-phenyl groups are trans with respect to each other. PMID- 1610531 TI - Structure of 6-fluoro-1 beta,2 beta-methylene-3,20-dioxo-9 beta,10 alpha-pregna 4,6-dien-17 alpha-yl acetate. AB - C24H29FO4, Mr = 400.5, orthorhombic, P2(1)2(1)2(1), a = 12.207 (1), b = 14.715 (1), c = 11.572 (1) A, V = 2078.7 (5) A3, Z = 4, Dx = 1.28 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 7.62 cm-1, F(000) = 856, T = 291 K, final R = 0.041 for 2230 observed reflections. The A and B rings assume flat boat and 9 beta,10 alpha half-chair conformations, with asymmetry parameters delta C3s = 1.5, delta C1,2s = 11.2 and delta C6,7(2) = 3.1, delta C7s = 15.0, respectively. PMID- 1610533 TI - Business and profits can benefit by employing part-time workers. PMID- 1610532 TI - Working in harmony. PMID- 1610534 TI - Parents should be reminded about the benefits of dental fluorides. PMID- 1610535 TI - Where does your office draw the line when it comes to personal business? PMID- 1610536 TI - Adding minor ortho procedures can be mental boost for staff. PMID- 1610537 TI - Ambulatory blood pressure monitoring: a must in the future? PMID- 1610538 TI - Transgenic mice as models for heritable diseases. AB - The development of methods for introduction of foreign DNA stably into genome of experimental animals has opened new possibilities to study the effects of mutations in complex gene-protein systems at the level of the entire organism. Information from such experiments is directly applicable to understanding of pathogenetic mechanisms in hereditary diseases and to designing of new therapeutic approaches. Techniques are currently available for studying both dominant mutations, introduced usually by microinjection, and recessive mutations introduced by homologous recombination employing the pluripotent embryonic stem cells. It remains to be emphasized, however, that the information which can be obtained with these techniques is optimal when sufficient background information is available on the protein system in question. The purpose of this review is to describe how the transgenic mouse methodology has increased our understanding of molecular basis of diseases both at the level of protein function and gene regulation. PMID- 1610539 TI - Comparison between lovastatin and cholestyramine in the treatment of moderate to severe primary hypercholesterolaemia. AB - 120 patients (64 men, 56 women) aged 19-66 years with primary hypercholesterolaemia (mean serum total cholesterol 10.1 mmol/l, range 6.5-16.3 mmol/l) with normal or moderately raised concentrations of serum triglycerides were randomised after four weeks' diet and four weeks' diet+placebo phase either to cholestyramine (40 patients) or lovastatin (80 patients) treatments for the succeeding 12 weeks. The maximal daily doses were 24 g of cholestyramine and 80 mg of lovastatin. The baseline data of the treatment groups were comparable with the exception of HDL-cholesterol concentrations, which were lower in the lovastatin group. The mean reductions in total serum cholesterol concentrations were 24.3% for cholestyramine (P less than or equal to 0.01) and 33.4% for lovastatin (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), in LDL-cholesterol 32.1% (P less than or equal to 0.01) and 40.7% (P less than or equal to 0.01) (P less than or equal to 0.05 between the treatment groups) and in apolipoprotein B 23.3% (P less than or equal to 0.01) and 33.3% (P less than or equal to 0.01) (P less than or equal to 0.01 between the treatment groups), respectively. Lovastatin was the only drug to reduce serum triglyceride concentrations, it did so by 26.0%. HDL-cholesterol increased by 7.7% (P = NS) when cholestyramine was taken and by 13.5% (P less than or equal to 0.05) with lovastatin (P = NS between the treatment groups). Apolipoprotein A1 remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610540 TI - Liver transplantation restores low serum levels of very low density and high density lipoproteins in end-stage primary biliary cirrhosis. AB - Amounts of serum lipids were determined in 10 women suffering from end-stage primary biliary cirrhosis (PBC) in order to evaluate the concentrations of and changes in very low density (VLDL), high density (HDL) lipoprotein cholesterol and apoprotein A-I before and after liver transplantation. The concentrations of some preoperative serum total lipids, especially HDL cholesterol and VLDL triglyceride, and apoprotein A-I, were significantly lower, but those of serum total triglycerides and cholestanol (a metabolite of cholesterol) were higher in the PBC patients than in 12 controls matched for age, sex, and body mass index. The relation between the serum concentrations of HDL cholesterol and cholestanol was markedly different before transplantation in the PBC group and in the control group. Liver transplantation was followed by a significant and rapid increase in serum apoprotein A-I and HDL cholesterol concentrations, which were affected by CMV and Klebsiella infections and acute rejections and immunosuppressive treatments. As a result the patients serum values did not quite return to normal during the three month follow up. The concentrations of serum VLDL cholesterol, triglycerides and cholestanol returned to normal during the follow up, and the changes in cholestanol were inversely related to the increases in amounts of HDL cholesterol. Thus, the restoration of low HDL concentrations after liver transplantation suggests that the liver plays a key role in HDL metabolism and indicates that concentrations of serum HDL cholesterol may be useful in monitoring the recovery of liver function. PMID- 1610541 TI - Pure red-cell aplasia due to parvovirus B19 infection in a patient with AIDS related complex. PMID- 1610542 TI - Facial muscles: a window to unconsciousness. PMID- 1610543 TI - Artificial insemination--where do we stand now? PMID- 1610544 TI - Genetic approaches to hypertension. AB - Essential hypertension is a complex clinical disorder in which multiple environmental and genetic factors interact to increase blood pressure. To search for chromosome regions that contain genes regulating blood pressure, some investigators have begun to conduct linkage studies in rodent models of spontaneous hypertension. Preliminary results suggest that in the rat, blood pressure regulatory genes may be located in the vicinity of the kallikrein gene family on chromosome 1, the gene for angiotensin converting enzyme on chromosome 10, the renin gene on chromosome 13, and the major histocompatibility complex on chromosome 20. Some studies have also suggested that blood pressure regulatory loci may be located on the sex chromosomes. Although comparisons between humans and animals should be made with caution, it is hoped that the identification of genes regulating blood pressure in the rat might shed light on the pathogenesis of hypertension in humans. PMID- 1610545 TI - Implications of recent results of long term multifactorial primary prevention of cardiovascular diseases. AB - Multifactorial primary prevention trials for reduction of cardiovascular diseases have engendered disappointing results because beneficial in-trial prevention has not been obtained consistently even when risk factor levels have been significantly improved. In addition, long term follow up studies, including post trial periods, have revealed diminished or disappeared differences in risk factor levels between treated and control groups; total and coronary mortality differences have also been reduced or the death rates have even been increased during the post-trial period of treated group over those of control subjects in a study with a consistent coronary risk reduction during the intervention period. Reasons for this enhanced coronary mortality cannot be pointed out but drug treatment, especially beta-blocking agents in mild hypertension, should be studied more carefully. Despite this discouraging mortality finding multifactorial prevention with simultaneous reduction of several coronary risk factors sounds useful provided that pharmacological prevention could be selected to give more benefit than harm. PMID- 1610547 TI - Ultrastructure of human osteoblasts and associated matrix in culture. AB - The ultrastructure, as visualized by transmission electron microscopy, of cells obtained from human bone explants and subsequently cultured is described along with the electron microscopic appearance of the associated intercellular matrix. The cells were characterized as osteoblasts on the basis of immunohistochemical, enzymatic, and functional criteria. Although the osteoblasts could be cultured in standard culture media and always appeared singly, not forming syncytia, the cultures were eventually confluent and formed multilayers. The cells were fusiform or cuboidal with diameters ranging between 10-15 microns. The cytoplasm was characterized by numerous large mitochondria, and especially by a very prominent RER. The intercellular matrix was woven with collagen fibres surrounding large numbers of matrix vesicles. In areas with matrix vesicles, evidence for osteoblast activity, i.e. mineralization related to matrix vesicles, could be observed after incubation with beta-glycerophosphate. In conclusion, we provide evidence that human osteoblasts cultured in vitro synthesize collagen and produce a matrix with vesicles capable of initiating mineralization processes. PMID- 1610546 TI - Screening method for beta-lactamase substrate profiles. AB - A disc diffusion method, based on the idea of Klundert, for screening of substrate profiles of beta-lactamases was developed in order to perform epidemiological studies. The method was tested against 30 different reference beta-lactamases and 59 clinical isolates known to produce TEM-1, SHV-1 and BRO-1. The reproducibility and discriminating power of the disc diffusion method made it possible to differentiate between eight types of substrate profiles for the 30 reference beta-lactamases and to differentiate between TEM-1, SHV-1 and BRO-1 from clinical isolates. In combination with analytical isoelectric focusing the disc diffusion method gives a reliable identification of beta-lactamases. PMID- 1610548 TI - Use of o-phthalaldehyde to detect O-phosphorylethanolamine in bacterial lipopolysaccharide. AB - We have developed a method to measure O-phosphorylethanolamine groups in bacterial lipopolysaccharide using a fluorescent reagent, o-phthalaldehyde. The optimal excitation and emission wavelengths were 335 nm and 450 nm, respectively. The reaction was pH-dependent with an optimum at pH 10.5. The maximum fluorescence intensity occurred two min after mixing lipopolysaccharide with the reagent at pH 10.5. The assay was linear over a range of 1 microgram to 100 micrograms of lipopolysaccharide. When we compared the amount of primary amine (as O-phosphorylethanolamine) in native and p-hydroxyphenylacetic acid derivatized lipopolysaccharide, we found that 97% of amine groups in native lipopolysaccharide were derivatized by p-hydroxyphenylacetic acid in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. PMID- 1610549 TI - Interleukins increase surface ganglioside expression of pancreatic islet cells in vitro. AB - This experiment was conducted in order to investigate whether expression of gangliosides on islet cell surface in vitro is influenced by cytokines, especially interleukin 1. Islets from adult Lewis rats were incubated with different concentrations of recombinant-derived human cytokines. Following dispase treatment, the single cells were labeled with monoclonal antiganglioside antibodies A2B5 or R2D6, and conjugate. Both are directed against beta cells; A2B5 is recognized to bind specifically to pancreatic islet cells, while R2D6 is shown to bind no other pancreatic cells than beta cells. Surface labeling was evaluated in blind trials using a fluorescence microscope and a fluorescence activated cell sorter (FACS). A2B5 staining demonstrated a significantly higher number of labeled cells after incubation with interleukin 1 alpha (14.9% +/- 2.8; p less than 0.005), interleukin 1 beta (23.2% +/- 4.2; p less than 0.0005) or TNF alpha (16.1% +/- 4.0; p = 0.005) compared to endotoxin controls (4.1% +/- 1.1). Interleukin 1 beta (9.5% +/- 1.5; p less than 0.005) showed a significantly increased number of R2D6-stained cells (control: 2.3% +/- 1.3). A similar but not significant effect was seen with interleukin 1 alpha and TNF alpha. Interleukin 6 had no effect on the antigen expression. The intensity of labeling was elevated among interleukin 1 beta-incubated cells compared to control samples. Thus, treatment of islets with different cytokines, especially interleukin 1 beta, increases surface antigen expression. We suggest that this mechanism of action in vitro may be of importance for the putative diabetogenic effect of interleukin 1. PMID- 1610550 TI - An ultrastructural and cytochemical study of the pulmonary lesions and multinucleate giant cells in porcine dermatosis vegetans. AB - The pulmonary lesions and multinucleate giant cell formations in porcine dermatosis vegetans were studied ultrastructurally and cytochemically in seven affected pigs that ranged from one to 120 days of age. At birth, no pulmonary lesions were observed. By seven days of age, there was a moderate infiltration of monocytes/macrophages in the alveoli and interstitium. These changes progressed, and by two weeks of age there was pronounced infiltration of macrophages and lymphocytes in the alveoli. Close apposition of macrophages and lymphocytes was observed, and cellular contact was demonstrated. By three to four weeks of age, small aggregates with epithelioid cells, macrophages, and lymphocytes resembling granulomas were present. In an older pig, aged four months, the inflammatory changes waned. Large macrophages, and large and small multinucleate cells shared common morphological characteristics of cytoplasm endowed with organelles, primary and secondary lysosomes, Golgi profiles, and granular endoplasmic reticulum. Cytochemically, macrophages and MGCs were positive for acid phosphatase. The present study showed that the initial pulmonary changes share morphological characteristics with a granulomatous inflammatory response, and evolve into small granulomas with macrophages, epithelioid cells and lymphocytes. Morphologically, these changes share characteristics with epithelioid cell granulomas. Macrophages and MGCs share common ultrastructural traits, and are positive for acid phosphatase. MGCs seem to evolve in the course of the granulomatous inflammatory response and are probably of monocyte/macrophage origin. PMID- 1610551 TI - Inducible beta-lactamases in clinical isolates of non-aeruginosa Pseudomonas. AB - The incidence of antimicrobial resistance and expression of imipenem-inducible beta-lactamase were examined in 22 strains of non-aeruginosa Pseudomonas isolated from clinical specimens. The percentage of strains resistant to form one to eight antibiotics was 45. The most active antibiotics against all strains were norfloxacin, ciprofloxacin and imipenem. Eighteen out of the 22 strains were positive for beta-lactamase in a spectrophotometric assay using nitrocefin as substrate. A low inducible beta-lactamase specific activity (0.001-0.999 nmoles nitrocefin hydrolyzed/min/mg protein) was found in twelve strains whereas six strains had a relatively high specific activity (3.5-159.8 nmoles nitrocefin hydrolyzed/min/mg protein). Five strains representing different Pseudomonas spp. and showing high beta-lactamase activity were studied further. Crude enzymes from two species (Pseudomonas mendocina, Pseudomonas acidovorans) hydrolyzed cefazolin at a higher rate than penicillin and ampicillin. All enzymes from the five species were inhibited by cloxacillin and p-chloromercuribenzoate (1 mM), but were insensitive to inhibition by clavulanic acid, ethylenediamine acetic acid (EDTA) at the same concentration. The isoelectric point and molecular weight of the main beta-lactamase band from the 5 species were 6.5-6.8 and 47,000 respectively. PMID- 1610552 TI - Enhancement of normal polymorphonuclear cells respiratory burst in ascitic fluid by fibronectin. Comparison between cirrhotic and malignant ascitic fluids. AB - The chemiluminescence (CL) response of normal peripheral blood polymorphonuclear cells (PMN) in ascitic fluids (cirrhotic = 32; malignant = 17) was studied independently of the ascitic fluid complement activity. CL response and fibronectin levels were higher in malignant ascitic fluid than in cirrhotic ascitic fluid (p less than 0.001). Addition of pure fibronectin or malignant ascitic fluids to cirrhotic ascitic fluids increased the CL response of normal PMN. These findings suggest that the susceptibility of cirrhotic patients to spontaneous bacterial peritonitis (SBP) is a multifactorial defect involving factors distinct from low C3 levels. Fibronectin is an important factor in the promotion of the respiratory burst of normal PMN stimulated by opsonized zymosan or PMA in ascitic fluid. Our results suggest that low levels of ascitic fluid fibronectin could partly explain the high susceptibility of cirrhotic patients to spontaneous bacterial peritonitis. PMID- 1610553 TI - Ultrastructural study of the response of cells infected in vitro with causative agent of spotted fever group rickettsiosis in Japan. AB - The response of host cells L929 infected with causative agent of spotted fever group (SFG) rickettsiosis in Japan, the Katayama strain, was studied by electron microscopy. The rickettsiae penetrated the cytoplasm and multiplied here and after prolonged incubation progressed into the dilated cisternae of rough endoplasmic reticulum (rER), the perinuclear space, the deep invaginated nuclear membrane, and then the nucleoplasm of the host cells. The intranuclear rickettsiae showed different states: one type was enclosed by the double membrane of the host cell and the other type was free in the nucleoplasm. In addition to these double membrane-bound and membrane-free intranuclear rickettsiae, various membrane structures, including rER-like structures, were also found in the nucleus. The cells infected with the rickettsiae underwent distinctive morphological alterations which occurred mainly within intracellular membranes of the host cells. These findings indicate the possibility that the intracellular membranes are characteristic cytopathological sites in rickettsia-host cell interaction, and that these alterations may be related to a possible route of rickettsial penetration into the nucleus: passage through vesicles formed from invaginations in the nuclear membrane. PMID- 1610554 TI - Role of streptococcal IgG Fc receptor in tissue deposition of IgG in rabbits immunized with Streptococcus pyogenes. AB - Induction of anti-IgG during hyperimmunization of rabbit with Streptococcus pyogenes (group A streptococci; GAS) was previously shown to require the presence of IgG Fc receptors (FcR) in the vaccine strain. In the present work, we examined whether streptococcal FcR activity might also be of importance for heart and kidney deposition of IgG, known to occur in poststreptococcal sequelae as well as during experimental immunization of animals. Each of three IgG-binding (GAS types M1, M12 and M22) and two non-binding (GAS type T27 and S. agalactiae (GBS) type Ia) streptococcal strains were used for intravenous immunization of rabbits during two periods of eight and six weeks, respectively, separated by an interval of one month. Before use, vaccine strains were treated with KSCN and carefully washed in order to remove any surface-bound immunoglobulins. No deaths occurred among injected rabbits. No tissue deposition was elicited by the GAS type T27 or the GBS strain. In contrast, the strains of types M1, M12 and M22 all induced deposits of IgG in kidney and heart tissue, beginning during the first immunization period. In two tested animals, receiving GAS of types M1 or M22, circulating immune complexes containing anti-IgG antibodies were also detected. Finally, serum autoantibodies reacting with preparations of heart and kidney, but not lung or liver, were demonstrated in each of six animals receiving M1 or M22, reaching maximum levels during reimmunization; such antibodies were not evoked by the two strains not binding IgG. Our results suggest that, in GAS with capacity for non-immune binding of IgG, triggering of anti-IgG acted to enhance tissue deposition of IgG or immune complexes in immunized rabbits. Furthermore tissue specific antibodies were elicited only by the IgG-binding strains and occurred comparatively late during immunization, suggesting that those antibodies might have been triggered due to the exposition of hidden kidney and heart determinants. PMID- 1610555 TI - The international contribution to the standardization of biological substances. III. Biological standardization and the World Health Organization 1947-1990. Specific activities and commentary. PMID- 1610556 TI - A new microtitration method for the enumeration of contagious bovine pleuropneumonia (CBPP) vaccines. AB - A new method is proposed for the microtitration of CBPP vaccines by performing eight parallel endpoint two-fold dilutions. When performed on a 96-well plate, it gives a titre with a precision of +/- 0.2 log10. By comparison, the established method, performed in tubes, gives a precision of only +/- 0.6 log10. The adaptation to microtitre plates allows much more economical culture of larger numbers of samples. Statistical analysis permits determination of vial-to-vial homogeneity of a batch and calculation of a titre with a precision of +/- 0.09 log10. The new method may be applied for the titration of mycoplasmas. PMID- 1610557 TI - Simplified activity evaluation of several tetanus vaccines. AB - The activity of several Tetanus Toxoids, Adsorbed, (commercial vaccines and references) were tested in mice in comparison with a standard, by a simple method, easier than the official challenge test (WHO and European Pharmacopoeia): the Tetanus Antitoxin level was titrated by agglutination of sensitized turkey red blood cells after immunization by the toxoids. Immuno-stimulation by the Pertussis component in associated vaccines was studied and the results with the conventional and the acellular Pertussis preparations were prepared. The method was also found to be suitable for Tetanus Toxoids, Non-Adsorbed, when a booster effect was used, except for the adjuvant-free polymerized antigen (POLAN) which did not require a booster, since it gave almost as good results as conventional adsorbed tetanus vaccines. PMID- 1610558 TI - A modified rapid enzyme immunoassay for the detection of rabies and rabies related viruses: RREID-lyssa. AB - This paper presents a modification of the previously described Rapid Rabies Enzyme Immuno-Diagnosis test (RREID) by using biotinylated antibodies, streptavidin conjugate and a mixture of monospecific polyclonal antibodies against several lyssaviruses. In the modified technique (RREID-lyssa), microplates were sensitized with a mixture of purified antibodies against ribonucleoprotein (RNP) from Pasteur virus (Lyssavirus serotype 1), European Bat Lyssavirus (EBL, unclassified) and Mokola virus (Lyssavirus serotype 3). Bound RNP was detected by the same antibodies labelled with biotin and peroxidase strepavidin conjugate. These techniques were used for the detection of RNP of different Lyssavirus serotypes (rabies and rabies-related viruses). For lyssavirus specimens of serotype 1, the threshold of detection of RREID and RREID lyssa were similar. However, a smaller amount of labelled antibodies was needed when biotinylated antibodies were used. For specimens infected by rabies-related strains (serotypes 2, 3, 4 and EBL), the threshold of detection of the RREID lyssa was between two and 512 times lower than with the RREID. The sensitivity and the specificity of the RREID-lyssa for rabies virus (serotype 1) when tested on a small field trial (53 specimens) were found to be identical to the RREID. Consequently, RREID-lyssa can be a useful tool for diagnostic laboratories that receive specimens infected by rabies-related viruses. PMID- 1610559 TI - Polyvinyl formal surface promotes continuous growth of Vero cells in protein-free medium. AB - The effect of polyvinyl formal (PVF) culture surface on the growth of 10 mammalian continuous cell lines, including Swiss 3T6, NCTC clone 929 L, BHK-21 clone 13, CHO-K1, PK 15, A 431, HeLa, MDCK, LLC-MK2 and Vero in protein-free 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F12 supplemented with trace elements and L-ascorbic acid 2-phosphate, was investigated. Most of the cell lines showed only some initial proliferation on PVF similar to the polystyrene (PS) surface of commercially available culture flasks. In contrast, proliferation of monkey kidney cell line Vero was by far greater on PVF than on PS or poly-D-lysine treated culture surface. In addition, Vero cells on PVF could be subcultured in the protein-free medium without any significant decrease of growth rate in successive passages. These results showed that PVF provides a culture surface which selectively promotes continuous growth of Vero cells in protein-free, chemically defined medium. PMID- 1610560 TI - Determination of antibodies to pertussis toxin in working reference preparations of anti-pertussis sera from various national control laboratories. AB - Working reference preparations of anti-pertussis sera from various National Control Laboratories were assayed for anti-PT antibodies by standardized ELISA and toxin neutralization (Nt) test. Both the ELISA and Nt tests gave highly reproducible results for various preparations when these preparations were assayed repeatedly on different days. Various working reference preparations were assigned units against the proposed International standard for anti-pertussis serum (JNIH-10) assuming its unitage of 250. Assigning unitage to various preparations would help in comparing results of ELISA and Nt tests for anti-PT antibodies reported in various studies. PMID- 1610561 TI - A collaborative study to examine the sensitivity and reproducibility of assays for the detection of DNA in biologicals derived from continuous cell lines. AB - This report describes the results of a collaborative study which was set up to examine the sensitivity and reproducibility of DNA assays performed by different laboratories. Fifteen laboratories analysed 12 samples containing different amounts of DNA and protein. The study revealed a high degree of variability between laboratories in determining the DNA content of the test samples. PMID- 1610562 TI - A labile period in the determination of the anterior-posterior axis during early neural development in Xenopus. AB - The process by which the vertebrate central nervous system acquires its regional properties remains a central problem in developmental biology. It is generally argued that at early gastrula stages the dorsal mesoderm possesses precise anterior-posterior positional information, which is subsequently imparted to the overlying ectoderm. However, using regionally specific gene probes to monitor regional responses in Xenopus embryos, we find that anterior-posterior properties are not fixed until early neurula stages. During gastrulation the regional inducing capacities of the dorsal mesoderm as well as the regional responses of the presumptive neural ectoderm are activated along the entire anterior-posterior axis when these properties are assayed in recombinant and explant experiments, respectively. Restriction of regional inducing capacity in the mesoderm and responsiveness in the neural ectoderm occur only at neural plate stages. PMID- 1610563 TI - mip causes hyperinnervation of a retinotopic map in Drosophila by excessive recruitment of R7 photoreceptor cells. AB - The two central photoreceptor neurons of the Drosophila eye, R7 and R8, form a retinotopic map in the optic lobe of the fly brain. We have developed a technique that allows us to visualize the projections of these neurons with high resolution. Using this technique, we have identified a new mutant, mip (more inner photoreceptors), in which this map shows a striking hyperinnervation. The extra terminals in the brain derive from an excessive recruitment of sevenless independent R7 photoreceptor cells during eye development. The original R7, however, remains sevenless responsive. The behavior of this gene suggests that recruitment to the R7 pathway, and possibly to multiple programs in ommatidial assembly, is partially regulated by inhibition. PMID- 1610565 TI - Differential expression of K+ channel mRNAs in the rat brain and down-regulation in the hippocampus following seizures. AB - K+ channels are major determinants of membrane excitability. Differences in neuronal excitability within the nervous system may arise from differential expression of K+ channel genes, regulated spatially in a cell type-specific manner, or temporally in response to neuronal activity. We have compared the distribution of mRNAs of three K+ channel genes, Kv1.1, Kv1.2, and Kv4.2 in rat brain, and examined activity-dependent changes following treatment with the convulsant drug pentylenetetrazole. Both regional and cell type-specific differences of K+ channel gene expression were found. In addition, seizure activity caused a reduction of Kv1.2 and Kv4.2 mRNAs in the dentate granule cells of the hippocampus, raising the possibility that K+ channel gene regulation may play a role in long-term neuronal plasticity. PMID- 1610564 TI - Cloning, expression during development, and evidence for release of a trophic factor for ciliary ganglion neurons. AB - Ciliary ganglion (CG) neurons undergo a period of cell death during development that may be regulated by the limited availability of trophic factor produced by their target tissues. We have previously reported the purification of a ciliary neurotrophic factor from adult chick sciatic nerve that we called growth promoting activity (GPA). Here we demonstrate that GPA can be purified and cloned from embryonic day 15 (E15) chick eyes, which contain all the target tissues of the CG. Our studies show the following: GPA mRNA is induced in embryonic chick eyes during the period of CG neuron cell death; GPA mRNA is expressed specifically in the layer of the eye that contains the targets of the CG and in primary cultures of smooth muscle cells isolated from the choroid layer of the eye; and biologically active GPA is released from cells transfected with a GPA cDNA. PMID- 1610566 TI - Phase-dependent contributions from Ca2+ entry and Ca2+ release to caffeine induced [Ca2+]i oscillations in bullfrog sympathetic neurons. AB - Sympathetic neurons display robust [Ca2+]i oscillations in response to caffeine and mild depolarization. Oscillations occur at constant membrane potential, ruling out voltage-dependent changes in plasma membrane conductance. They are terminated by ryanodine, implicating Ca(2+)-induced Ca2+ release. Ca2+ entry is necessary for sustained oscillatory activity, but its importance varies within the oscillatory cycle: the slow interspike rise in [Ca2+]i requires Ca2+ entry, but the rapid upstroke does not, indicating that it reflects internal Ca2+ release. Sudden alterations in [Ca2+]o, [K+]o, or [caffeine]o produce immediate changes in d[Ca2+]i/dt and provide information about the relative rates of surface membrane Ca2+ transport as well as uptake and release by internal stores. Based on our results, [Ca2+]i oscillations can be explained in terms of coordinated changes in Ca2+ fluxes across surface and store membranes. PMID- 1610567 TI - BDNF mRNA expression in the developing rat brain following kainic acid-induced seizure activity. AB - Brain-derived neurotrophic factor (BDNF) mRNA expression was studied in the hippocampus at various developmental stages in normal rats and following kainic acid (KA)-induced seizure activity. Systemic administration of KA strongly elevated BDNF mRNA levels in all hippocampal subregions after postnatal day 21. In contrast, even though KA induced intense behavioral seizure activity at postnatal day 8, the seizures were not associated with elevations of BDNF mRNA levels, indicating a clear dissociation between behavioral seizures and increases in BDNF mRNA levels and contradicting the view that BDNF mRNA expression is principally regulated by neuronal activity. In the dentate gyrus at postnatal day 13, intense BDNF mRNA expression was limited to a defined area at the border between granule cell and molecular layers, suggesting the possibility that segregation of BDNF mRNA into defined subcellular compartments may play a role in establishing the well-delineated patterns of innervation in the hippocampus. PMID- 1610568 TI - Cloning of the cDNA for a novel photoreceptor membrane protein (rom-1) identifies a disk rim protein family implicated in human retinopathies. AB - The molecules essential to the continual morphogenesis and shedding of the opsin containing disks of vertebrate photoreceptors are largely unknown. We describe a 37 kd protein, rom-1, which is 35% identical and structurally similar to peripherin/retinal degeneration slow (rds). Like peripherin, rom-1 is a retina specific integral membrane protein localized to the photoreceptor disk rim. The two proteins are similarly oriented in the membrane, and each has a highly conserved (15/16 residues) cysteine- and proline-rich domain in the disk lumen. Although both rom-1 and peripherin form disulfide-linked dimers, they do not form heterodimers with each other, but appear to associate noncovalently. These results suggest both that rom-1 and peripherin are functionally related members of a new photoreceptor-specific protein family and that rom-1, like peripherin, is likely to be important to outer segment morphogenesis. The association of mutations in RDS with retinitis pigmentosa indicates that ROM1 is a strong candidate gene for human retinopathies. PMID- 1610569 TI - Neuronal cells are deficient in loading peptides onto MHC class I molecules. AB - Virally infected neurons avoid destruction by cytotoxic T lymphocytes (CTLs) by failing to express major histocompatibility complex (MHC) class I molecules. Like neurons in vivo and in primary culture, the OBL21 neuronal cell line expressed barely detectable levels of MHC class I molecules. This correlated with very low levels of mRNAs for the MHC class I heavy chains (alpha C). OBL21 cells also fail to provide MHC class I molecules with the peptides necessary for their efficient assembly and transport to the cell surface. This function can be restored by treatment with interferon-gamma (IFN-gamma). The mRNA for peptide transporters HAM1 and HAM2 was not detectable in OBL21 neuronal cells, but was induced by IFN gamma treatment. Hence, the ability of neurons to evade CTL-mediated killing results from expression at low levels of the MHC class I alpha C, the peptide transporters HAM1 and HAM2, and possibly other genes of the peptide-loading machinery. PMID- 1610570 TI - CNS glial cells support in vitro survival, division, and differentiation of dissociated olfactory neuronal progenitor cells. AB - Olfactory receptor neurons (ORNs) are replaced and differentiate in adult animals, but differentiation in dissociated cell culture has not been demonstrated. To test whether contact with the CNS regulates maturation, neonatal rat olfactory cells were grown on a culture substrate or on CNS astrocytes. Mature ORNs, immunopositive for olfactory marker protein (OMP), disappeared rapidly from both systems. Neurons positive for neuron-specific tubulin (immature and mature) disappeared from substrate-only cultures, but remained abundant in the cocultures. OMP-positive neurons reappeared after 10 days in vitro. Pulse labeling with [3H]thymidine showed extensive neurogenesis of both immature and mature olfactory neurons. This demonstrates, in vitro, both division and differentiation of olfactory progenitor cells. PMID- 1610571 TI - DNR in the OR: further questions. PMID- 1610572 TI - Do-not-resuscitate orders in the presurgical patient. AB - STUDY OBJECTIVE: To assess the policy and practice of anesthesiology departments in regard to their management of the presurgical do-not-resuscitate (DNR) patient. DESIGN: Questionnaire distributed to the program directors of 156 accredited residency programs in anesthesiology in the contiguous United States. SETTING: University hospital. MEASUREMENTS AND MAIN RESULTS: One hundred twelve of the 156 accredited U.S. programs responded to the questionnaire. The majority (81%) of programs that have a DNR policy for the presurgical patient suspend the order prior to surgery. However, only 50% of the institutions responding have standing policies, and of those that do not, only 40% plan to initiate such a policy. CONCLUSIONS: The need for a written policy for the DNR patient undergoing surgery is exemplified by the low percentage of institutions that have existing policies. PMID- 1610573 TI - Intraoperative warming therapies: a comparison of three devices. AB - STUDY OBJECTIVE: To compare the effectiveness of three commonly used intraoperative warming devices. DESIGN: A randomized, prospective clinical trial. SETTING: The surgical suite of a university medical center. PATIENTS: Twenty adult patients undergoing kidney transplantation for end-stage renal disease. INTERVENTIONS: Patients were assigned to one of four warming therapy groups: circulating-water blanket (40 degrees C), heated humidifier (40 degrees C), forced-air warmer (43 degrees C, blanket covering legs), or control (no extra warming). Intravenous fluids were warmed (37 degrees C), and fresh gas flow was 5 L/min for all groups. No passive heat and moisture exchangers were used. MEASUREMENTS AND MAIN RESULTS: The central temperature (tympanic membrane thermocouple) decreased approximately 1 degree C during the first hour of anesthesia in all groups. After three hours of anesthesia, the decrease in the tympanic membrane temperature from baseline (preinduction) was least in the forced-air warmer group (-0.5 degrees C +/- 0.4 degrees C), intermediate in the circulating-water blanket group (-1.2 degrees C +/- 0.4 degrees C), and greatest in the heated humidifier and control groups (-2.0 degrees C +/- 0.5 degrees C and -2.0 degrees C +/- 0.7 degrees C, respectively). Total cutaneous heat loss measured with distributed thermal flux transducers was approximately 35W (watts = joules/sec) less in the forced-air warmer group than in the others. Heat gain across the back from the circulating-water blanket was approximately 7W versus a loss of approximately 3W in patients lying on a standard foam mattress. CONCLUSION: The forced-air warmer applied to only a limited skin surface area transferred more heat and was clinically more effective (at maintaining central body temperature) than were the other devices. The characteristic early decrease in central temperature observed in all groups regardless of warming therapy is consistent with the theory of anesthetic-induced heat redistribution within the body. PMID- 1610574 TI - Frequency and severity of desaturation events during general anesthesia in children with and without upper respiratory infections. AB - STUDY OBJECTIVE: To determine whether anesthesia in the presence of a mild upper respiratory infection (URI) was associated with episodes of desaturation or reactive airway problems. DESIGN: A prospective study. SETTING: Inpatient and outpatient units of a university medical center. PATIENTS: Four hundred two pediatric patients. INTERVENTIONS: Patients were monitored with continuous recordings of oxygen saturation (SpO2), capnography, and electrocardiogram. A separate anesthesiologist was present throughout each case to observe for complications and interview the anesthesia team. The decision to anesthetize patients with a URI was left to the discretion of the anesthesia team. MEASUREMENTS AND MAIN RESULTS: Thirty patients with a URI and 372 patients without one were studied. One hundred ninety-six patients were managed with endotracheal intubation and 206 with face mask; 15 in each group had a URI. There was no increase in major desaturation events (SpO2 of 85% or less for 30 or more seconds) but minor desaturation events (SpO2 of 95% or less for 60 or more seconds) were increased (p = 0.02). There was no increased frequency of laryngospasm (1 in 30 vs. 22 in 372), but there was a higher frequency of bronchospasm in intubated patients (2 in 15 vs. 1 in 181; p = 0.016). CONCLUSIONS: Children with a mild URI have an increased frequency of minor desaturation episodes, and intubated patients with a URI have an increased frequency of bronchospasm. It appears that children with a mild URI may be safely anesthetized, since the problems encountered are generally easily treated and without long-term sequelae. PMID- 1610575 TI - Early anesthesia evaluation of the ambulatory surgical patient: does it really help? AB - STUDY OBJECTIVE: To evaluate whether early evaluation by the anesthesiologist is more beneficial for the ambulatory surgical patient than a day-of-surgery visit. DESIGN: A randomized study evaluating patients with different surgical procedures. SETTING: Ambulatory surgical outpatients at a university-affiliated integrated ambulatory surgical unit. PATIENTS: Sixty-three ASA physical status I and II women scheduled to undergo elective dilatation and curettage or gynecologic laser surgery. INTERVENTIONS: Approximately half of the patients received an early (1 to 7 days preoperative) anesthesia evaluation, and half received a day-of-surgery evaluation. All patients underwent the surgical procedures with a standardized general anesthetic. MEASUREMENTS AND MAIN RESULTS: The effect of an early versus a day-of-surgery anesthesia visit was evaluated with regard to patient anxiety levels; patient satisfaction with the surgical and anesthetic experience; operating room, recovery room, and ambulatory surgery unit time; anesthetic and analgesic requirements; and frequency of postoperative problems within 72 hours at home. There were no differences between the groups in demographic characteristics, anesthesia or analgesic requirements, degree of satisfaction with the ambulatory surgical experience, time spent in recovery room, or frequency of problems on postoperative follow-up. We were unable to demonstrate any differences between those patients seen early versus those seen on the day of surgery in anxiety levels preoperatively and postoperatively. CONCLUSIONS: Healthy ASA physical status I and II ambulatory surgical patients do not benefit from reducing preoperative anxiety by visiting the anesthesiologist prior to the day of surgery. PMID- 1610576 TI - Electroconvulsive therapy-induced cardiac arrhythmias during anesthesia with methohexital, thiamylal, or thiopental sodium. AB - STUDY OBJECTIVE: To determine the frequency of electroconvulsive therapy (ECT) induced arrhythmias under methohexital, thiamylal, or thiopental sodium anesthesia with and without atropine premedication. DESIGN: A randomized, double blind study, placebo-controlled for atropine. SETTING: The inpatient psychiatric unit at a university medical center. PATIENTS: Forty-nine patients scheduled for ECT. INTERVENTIONS: Atropine 0.6 mg intravenously (IV) or an equal volume of normal saline IV was given before IV induction of anesthesia with methohexital 0.5 to 1.0 mg/kg, thiamylal 1.5 to 2.5 mg/kg, or thiopental sodium 1.5 to 2.5 mg/kg. MEASUREMENTS AND MAIN RESULTS: Single-lead electrocardiogram (ECG) recordings were made for 1 minute before induction, during induction of anesthesia, and for 5 minutes after the ECT stimulus. Each ECG was evaluated for arrhythmias and evidence of ischemia in a blinded fashion. Blood pressure and ECG evidence of ischemia did not differ among the groups. Seizure duration was significantly (p less than 0.05) prolonged by a mean of 5 seconds during methohexital anesthesia compared with thiopental sodium and thiamylal (47.6 +/- 18.6 seconds, 42.7 +/- 13.2 seconds, and 42.7 +/- 15.2 seconds, respectively). The frequency of sinus bradycardia was decreased (p less than 0.05) with methohexital (8%) compared with thiopental sodium (20%) and thiamylal (20%). The frequency of premature atrial contractions was decreased (p less than 0.05) with methohexital (43%) compared with thiamylal (61%) but not with thiopental sodium (57%). The frequency of premature ventricular contractions was decreased (p less than 0.05) with methohexital (27%) compared with thiopental sodium (44%) but not with thiamylal (40%). Atropine decreased the frequency of bradycardia (9% vs. 24%) and premature atrial contractions (47% vs. 61%) and increased the frequency of sinus tachycardia (88% vs. 75%). CONCLUSIONS: These data suggest that anesthesia for ECT therapy should be induced with methohexital to minimize the possibility of potentially life-threatening cardiac arrhythmias. Atropine premedication may further decrease the frequency of premature atrial contractions and bradycardia, while increasing the frequency of tachycardia. PMID- 1610577 TI - Midazolam in combination with propofol for sedation during local anesthesia. AB - STUDY OBJECTIVE: To compare the sedative, anxiolytic, and amnestic effects, as well as the recovery characteristics, when midazolam (vs. a placebo) is administered to patients receiving a propofol infusion for sedation during local anesthesia. DESIGN: Randomized, double-blind, placebo-controlled study to evaluate the perioperative effects of intravenous (IV) midazolam. SETTING: Outpatient surgery center of a university-affiliated medical center. PATIENTS: One hundred thirty-nine consenting, ASA physical status I, II, and III outpatients undergoing elective surgical procedures under local anesthesia. INTERVENTIONS: Patients were randomly assigned to receive either midazolam 2 mg IV or saline 2 ml IV prior to injection of local anesthesia. Intraoperative sedation was maintained using a variable-rate propofol infusion. MEASUREMENTS AND MAIN RESULTS: Preoperative assessment of sedation, anxiety, and amnesia was performed before and after IV midazolam. Intraoperative evaluations included level of sedation, as well as cardiovascular and respiratory measurements, at 1- to 5-minute intervals during the operation. Postoperatively, recovery of psychomotor function and patients' subjective feelings were assessed using the visual analog scale and questionnaires. Amnesia was assessed using picture recall during the perioperative period. In the operating room, midazolam 2 mg IV, compared with the placebo, produced a significantly greater increase in patients' level of sedation (7 +/- 13 mm to 49 +/- 21 mm for midazolam vs. 8 +/- 11 mm to 19 +/- 21 mm for the placebo; p less than 0.01) and a greater decrease in anxiety level (62 +/- 25 mm to 21 +/- 21 mm for midazolam vs. 54 +/- 27 mm to 53 +/- 22 mm for the placebo; p less than 0.01). Although the propofol dosage requirements to maintain comparable levels of sedation were similar in both groups, midazolam decreased patients' recall of intraoperative events (e.g., propofol-induced pain on injection and discomfort with local anesthetic injection) without significantly altering cardiorespiratory parameters or prolonging times to ambulation and discharge from the outpatient facility. CONCLUSIONS: Premedication with midazolam 2 mg IV produced increased sedation, amnesia, and anxiolysis when administered immediately prior to the propofol infusion as part of a sedation technique for outpatient surgery. This combination did not prolong the recovery room stay when compared with propofol alone. PMID- 1610578 TI - Which is the safest endotracheal tube for use with the CO2 laser? A comparative study. AB - STUDY OBJECTIVE: To compare the efficacy of special endotracheal tubes manufactured for carbon dioxide (CO2) laser surgery with foil-wrapped and plain red rubber (RR) endotracheal tubes. SETTING: Research laboratory of a metropolitan, university-affiliated medical center. DESIGN AND INTERVENTIONS: Six types of endotracheal tubes were studied. Each had 5 L/min of oxygen passing through it and was exposed to 69 watts of continuous CO2 laser radiation for 1 minute or until combustion occurred. MEASUREMENTS AND MAIN RESULTS: The plain RR endotracheal tube burned within 15 seconds of laser impact. Aluminum foil-wrapped and copper foil-wrapped RR endotracheal tubes were not affected by the CO2 laser. The shaft of a specially manufactured stainless steel endotracheal tube was not affected by 1 minute of CO2 laser exposure. The shafts of two special endotracheal tubes made of silicone and metal burned vigorously under laser fire. CONCLUSION: Copper foil-wrapped RR tubes, aluminum foil-wrapped RR tubes, or stainless steel tubes are recommended for laser airway surgery. PMID- 1610579 TI - The effect of the prone position on venous pressure and blood loss during lumbar laminectomy. AB - STUDY OBJECTIVE: To determine the effects of three different prone support systems (Andrews spinal surgery frame, Cloward surgical saddle, and longitudinal bolsters) on inferior vena cava (IVC) and superior vena cava (SVC) pressures; the validity of measuring central venous pressure (CVP) for the determination of ideal positioning of the patient; and the relationship among frame type, blood loss, and hemodynamic measurements. DESIGN: Prospective, randomized study of the hemodynamic effects of the prone position. SETTING: Inpatient surgery at a university hospital (regional spinal cord injury treatment center). PATIENTS: Eighteen patients free of significant coexisting disease (ASA physical status I and II) undergoing elective lumbar laminectomy. INTERVENTIONS: Patients were assigned to one of three support frames and measurement of SVC pressure, IVC pressure, and mean arterial pressures (MAP) were obtained supine, prone, and after repositioning. These pressures and measured blood loss were obtained every 15 minutes during the surgical laminectomy portion of the procedure. MEASUREMENTS AND MAIN RESULTS: Patients positioned on the Andrews frame had decreased mean SVC and IVC pressures from 8.7 mmHg and 8.4 mmHg in the supine position to 3.3 mmHg and 1.8 mmHg in the prone position, respectively (p less than 0.001). Prone position CVP also was significantly lower in the Andrews group compared with that in the other two groups (p less than 0.001). Repositioning efforts did not significantly decrease CVP. Blood loss was higher in the Cloward group (1,150 +/- 989 ml) than in the Andrews (245 +/- 283 ml) and bolsters (262 +/- 188 ml) groups (p less than 0.02). CONCLUSIONS: Increased blood loss was not associated with increased SVC or IVC pressure, nor was there any significant correlation between any demographic or hemodynamic variable and blood loss. There was no evidence that CVP is useful in determining the ideal prone position in patients undergoing lumbar laminectomy. PMID- 1610580 TI - Management for electroconvulsive therapy of a patient with inoperable coronary artery disease and ankylosing spondylitis. AB - A 69-year-old male with severe coronary artery disease, ankylosing spondylitis, and severe major depression was scheduled for electroconvulsive therapy (ECT). The patient had previously failed or proved intolerant of antidepressant drug therapy. The nature and severity of the patient's diseases and complexity of potential interactions with ECT and anesthesia required sequential assessment of hemodynamic and airway tolerances with successive treatments. Despite substantial risks for particular patients, ECT may provide the only treatment option for life threatening psychiatric illness and warrants innovative approaches to anesthetic management. PMID- 1610581 TI - Management of a suspected and unsuspected difficult laryngoscopy with the laryngeal mask airway. AB - The laryngeal mask airway (LMA) is a new development in airway control. Presented here are two cases of difficult airway management--one anticipated, the other not anticipated--during which the LMA was used effectively. PMID- 1610583 TI - Total intravenous anesthesia with propofol for transsternal thymectomy in myasthenia gravis. AB - Patients with myasthenia gravis (MG) represent a significant management problem for the anesthesiologist. Anesthetic concerns center on the MG patient's unpredictable response to muscle relaxants and increased susceptibility to postoperative respiratory failure, resulting in prolonged dependence on mechanical ventilation. We describe the first reported use of total intravenous anesthesia with propofol to provide satisfactory surgical conditions in two patients with MG undergoing trans-sternal thymectomy. Propofol is a suitable drug for intubation and continuous infusion anesthesia, allowing fine control of anesthetic depth, good operating conditions, and a recovery profile suitable for MG patients undergoing surgery. PMID- 1610582 TI - Understanding and management of amniotic fluid embolism. AB - Amniotic fluid embolism (AFE) is a rare obstetric problem characterized by sudden onset of hypotension, hypoxemia, and coagulopathy. This case represents the difficulty in differentiating AFE from other etiologies of cardiopulmonary compromise. The definitive diagnosis of AFE is made at autopsy with the demonstration of fetal cell elements in the pulmonary vasculature. Diagnosis can be highly suspected if squamous cells and other debris of presumed fetal origin are demonstrated in blood aspirated from the central venous or pulmonary artery circulation of symptomatic parturients. Predisposing factors for AFE include advanced maternal age, multiparity, large fetal size, and short tumultuous labor, especially if uterine stimulants are used. Cardiopulmonary resuscitation is the key to the treatment of parturients with AFE. A pulmonary artery catheter can be helpful in diagnosis and hemodynamic management of parturients with AFE. PMID- 1610584 TI - Rapid orotracheal intubation in the clenched-jaw patient: a modification of the lightwand technique. AB - Emergency airway management of the patient with a clenched jaw can present a special challenge to the anesthesiologist. We describe four cases in which the patients had a clenched jaw and nasotracheal intubation was either contraindicated or several attempts had failed. All patients were successfully orotracheally intubated by a modification of the lightwand technique. PMID- 1610585 TI - The difficult airway: mechanisms for effective dissemination of critical information. AB - The perioperative management and dissemination of critical information regarding a patient with an unexpected difficult intubation, including successful application of a difficult airway algorithm (Figure 1), are described. Documentation and dissemination of critical information include entry of patient data into an in-hospital computerized Difficult Airway/Intubation Registry, simultaneous application of a highly visible Difficult Airway/Intubation Patient Wrist Band (coded for access to computer registry), summary reports distributed to health care providers, and enrollment of the patient in the Medic Alert Foundation International's newly established category difficult airway/intubation for 24-hour access. We postulate that the widespread use of the procedures described in this report may reduce the contribution of unexpected difficult airway/intubation to anesthetic morbidity and mortality. PMID- 1610586 TI - The laryngeal mask airway. AB - The laryngeal mask airway (LMA) is a new concept in airway management. A miniature inflatable mask is positioned in the hypopharynx, forming a low pressure seal around the laryngeal inlet. The mask is attached via a tube to the breathing circuit. It is inserted after induction of anesthesia without the need for muscle relaxants or laryngoscopy. The LMA can be used to facilitate both spontaneous and controlled ventilation in adults and children. The LMA has been used for a wide variety of surgical procedures but is probably best suited to short procedures, especially if a light general anesthetic is used in combination with a regional technique. It may be particularly useful in outpatient anesthesia, as it avoids the need for intubation or muscle relaxants. It can be used as an alternative to mask anesthesia or when an endotracheal tube would have been inserted to allow surgical access. It has been used successfully in cases of difficult or failed intubation, although its role here needs further appraisal. It does not protect against aspiration of stomach contents and should not be used when aspiration is a risk. Controversy exists regarding its use to facilitate positive-pressure ventilation (PPV) due to concern that gases under pressure may be forced into the stomach and predispose the patient to regurgitation. It may be more difficult to use in children. It is now widely used in the United Kingdom; however, it is not yet available for sale in the U.S. It has already had a major effect on practice in Britain and has the potential to do the same in the United States. PMID- 1610587 TI - Fiberoptic bronchoscopic guidance for intubating a child with Pierre-Robin syndrome. PMID- 1610588 TI - Regional anesthesia as anesthetic technique of choice in acute hepatic porphyria. PMID- 1610589 TI - Perioperative myocardial protection with the calcium antagonist diltiazem. AB - The effect of the calcium channel blocker, diltiazem, on cardiac performance was examined in 90 patients who underwent isolated aortic valve replacement for aortic valve diseases with marked left ventricular hypertrophy. The patients were randomly assigned to one of five groups dependent on the treatment plan with diltiazem: group 1, 5-day preoperative treatment with oral administration of 60 mg diltiazem 3 times daily, 10 mg diltiazem intravenously as a bolus dose before the beginning of the cardiopulmonary bypass, and 5 mg diltiazem intravenously 10 min before removal of aortic clamp; group 2, 5-day preoperative treatment with oral administration of 60 mg diltiazem 3 times daily; group 3, 10 mg diltiazem intravenously as a bolus dose before the beginning of CPB and 5 mg 10 min before removal of the aortic clamp; group 4, 15 mg diltiazem in 1000 ml cardioplegic solution, given as additive; group 5, control group not receiving diltiazem. All operative procedures were performed in an identical manner with an average cross clamping time of 57.7 min and cooling the heart down to 16 degrees-17 degrees septal temperature by perfusion of the coronary arteries with 4 degrees C cold cardioplegic solution. In each patient the heart rate (HR), cardiac output and cardiac index (CO, CI), stroke volume index (SVI), left ventricular stroke work index (LVSWI) and systemic vascular resistance index (SVRI) were recorded and calculated before and after the ischemic period. Transmural samples were obtained three times by needle biopsy technique from the anterior free wall of the heart. Analysis of the variables revealed that: (1) complete cessation of electromechanical activity was achieved significantly more rapidly in groups 1 and 3 than in the other groups; (2) recovery of sinus rhythm and function of the conductive system required significantly longer in groups 1 and 3; (3) the time related values of the important hemodynamic factors (CO, CI, LWSVI and SVRI) showed a significantly more effective postperfusion cardiac performance in groups 1 and 3 than in groups 2, 4 and 5. An oral dose of 180 mg diltiazem for 5 to 7 days preoperatively in combination with intravenous administration of 10 mg before the beginning of CPB and 5-10 mg during reperfusion can be recommended in patients undergoing open-heart surgery for isolated aortic valve diseases and left ventricular hypertrophy. PMID- 1610590 TI - Calcium antagonists--are they protective during intraoperative myocardial ischemia? PMID- 1610591 TI - Computed tomography for preoperative assessment of T3 and T4 bronchogenic carcinoma. AB - Between January 1986 and January 1991, 175 patients with suspected T3 or T4 bronchogenic carcinoma underwent computed tomographic (CT) examination of the chest before thoracotomy. We considered two groups of patients: group 1 includes 98 patients with a paramediastinal mass on standard chest X-ray; invasion of hilar and mediastinal structures was preoperatively investigated with CT and then assessed at thoracotomy. The sensitivity, specificity and accuracy were 72%, 75% and 73%, respectively; positive and negative predictive values were 71% and 76%. In group 2 77 patients had a peripheral tumor suspected of invading the parietal pleura and the soft tissues of the chest wall (patients with evident rib or vertebral invasion were not included). Sensitivity, specificity and accuracy of CT were 52%, 86% and 71%, respectively; positive and negative predictive values were 74% and 70%. We conclude that CT with injection of contrast material is indispensable when direct lung cancer infiltration must be ruled out; its accuracy is however not sufficient to be relied upon in all patients. PMID- 1610592 TI - Perfusion with low systemic heparinization during resection of descending thoracic aortic aneurysms. AB - Two series of 20 consecutive patients with aneurysms of the descending thoracic aorta (TAA) and thoraco-abdominal aorta (TAAA) underwent multisegmental aortic repair using either simple normothermic crossclamping and rapid reanastomosis (historic) or partial cardiopulmonary bypass (CPB) with heparin coated perfusion equipment and low systemic heparinization (actual). Chronic lesions were present in 14/20 patients (70%) for simple versus 13/20 (65%) for CPB (NS). Acute lesions (symptomatic less than 24 h) were present in 6/20 patients (30%) for simple versus 7/20 (35%) for CPB (NS). Dissecting lesions were observed in 4/20 patients (20%) for simple versus 8/20 (40%) for CPB (NS). Aneurysmal lesions were found in 16/20 patients (80%) for simple versus 12/20 (60%) for CPB (NS). Mean number of aortic segments (n = 8) resected was 3.2 +/- 1.1 for simple versus 4.0 +/- 1.2 for CPB (P less than 0.01). Replacement of the transdiaphragmatic aorta was performed in 10/20 patients (50%) for simple and 13/20 patients (65%) for CPB (NS). A heparin loading dose of 5000 IU for simple versus 100 IU/kg bodyweight for CPB was used. In the latter group, the activated clotting time was kept above 180 s during a mean perfusion time of 46 +/- 28 min at a mean pump flow of 2.2 +/ 0.7 l/min. Thirty-day survival for all (transdiaphragmatic) was 12/20 (5/10) patients for simple versus 20/20 (13/13) for CPB (P less than 0.002, P less than 0.01). One-year survival (all) was 11/20 patients (55%) for simple versus 19/20 (95%) for CPB (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610593 TI - Improved endothelial viability of heart valves cryopreserved by a new technique. AB - The aim of this study was to compare different techniques of aortic valve cryopreservation by studying the viability of the endothelial cells. Viability was assessed by measuring their in vitro prostacyclin (PGI2) production under basal and stimulated conditions. Fresh and cryopreserved porcine valves were incubated at 37 degrees C in tissue culture medium and PGI2 content in the medium was measured every 15 min up to 300 min. Cryopreservation by the older procedure A included 5% fetal calf serum (FCS) in the preservation medium, a plastic box inside a freezing plastic bag, a cooling schedule approximating -2 degrees C/min, a long thawing time and few dilution steps of the cryoprotectant dimethylsulphoxide (DMSO). The newer procedure B differed from A in packaging, freezing and thawing rates and DMSO dilution. Procedure C was similar to B with the exception that FCS was omitted. Leaflets preserved by procedure A produced significantly less prostacyclin as compared to those treated according to procedures B or C. We conclude that minor differences in the cryopreservation method can become critical to endothelial functional viability. PMID- 1610594 TI - Long-term results of porcine bioprostheses in the tricuspid position. AB - Between 1974 and 1990, 58 patients underwent tricuspid valve replacement with porcine bioprostheses (Hancock 42, Carpentier-Edwards 16) during multiple valve replacement (double, 21; triple, 37). Perioperative mortality was 12%; 16 patients died later, mostly from cardiac causes. Actuarial survival (1 patient lost to follow-up) was 81% +/- 11% at 5 years, and 60 +/- 17% at 10 years. Reoperation because of Hancock prosthesis deterioration was performed in 2 patients at 11 and 15 years, respectively. At last follow-up (mean 108 +/- 48 months), 82% of survivors (28/34) were functionally improved. Doppler echocardiography was performed in 29 patients in February 1991. In 21 patients, after 88 +/- 40 months of follow-up, the bioprosthesis was normal, there was no leaflet malformation, no significant tricuspid regurgitation and the mean diastolic transprosthetic gradient (DTPG) was 3.8 +/- 1.7 mmHg. In 7 patients (follow-up: 129 +/- 40 months, P less than 0.05), there was moderate dysfunction (all Hancock prostheses) with leaflet sclerosis, tricuspid regurgitation grade 2, and mean DTPG 5.7 +/- 1.8 mmHg (P less than 0.05). Only 1 patient (Hancock prosthesis implanted in 1981) had severe tricuspid prosthesis stenosis with very thickened leaflets and mean DTPG 13 mmHg. Pulmonary artery hypertension (most often fixed) was present in 11 patients, associated with a poor functional result and a significantly higher DTPG. We conclude that porcine bioprostheses in tricuspid position have an acceptable long-term durability and satisfactory performance. Prosthetic dysfunction correlates with the length of follow-up of patients and with the presence of fixed pulmonary artery hypertension. PMID- 1610596 TI - Carbomedics and St. Jude Medical bileaflet valves: an in vitro and in vivo comparison. AB - The hydrodynamic and haemodynamic function of 29 mm mitral and 23 mm aortic St Jude Medical (SJM) and CarboMedics (CM) heart valves have been compared in a pulsatile flow simulator in the laboratory and by doppler ultrasound in vivo. The laboratory studies showed that there was no significant difference in the pressure drop across the valves. The valves also had similar regurgitant volumes. Doppler ultrasound confirmed these results with a mean pressure drop of 12.9 +/- 5.5 mmHg across the CM aortic valves and 12.6 +/- 5.5 mmHg for the SJM aortic valves. The mean mitral diastolic pressure drops were 3.8 +/- 1.8 and 4.6 +/- 1.4 mmHg for the CM and SJM valves, respectively. Mild aortic regurgitation was detected in 5 of 14 patients in the CM group and 1 out of 6 patients in the SJM group, though none of the cases were clinically significant. Both the in vitro and in vivo results show these valves to have acceptable and comparable function. PMID- 1610597 TI - Technique of aortic valve replacement with the Edwards stentless aortic bioprosthesis 2500. AB - Aortic valve replacement with a stentless device ought to result in superior hemodynamic function, because obstructing stents and sewing rims are eliminated. From 15 June 1991 to 15 October 1991, 15 patients underwent aortic valve replacement with the newly designed Edwards stentless aortic bioprosthesis 2500. Patients' ages ranged from 51 to 70 years (mean 61 years). Preoperatively 4 patients presented with aortic regurgitation, 7 with aortic stenosis and 4 with combined lesions; 7 patients were male and 8 female. No additional cardiac or noncardiac diseases were encountered. The operations were performed under normothermic extracorporeal cardiopulmonary bypass and cold cardioplegic cardiac arrest. The implanted valves ranged from 21 mm to 27 mm in diameter. Ten patients received a subcoronary implantation with the lower row of stitches made up of interrupted sutures and the upper row of a continuous suture. In 5 patients the so-called miniroot technique was used, also with lower interrupted sutures and running upper sutures, after adaptation of coronary ostia to the performed openings in the graft. Aortic cross-clamp time ranged between 73 min and 94 min (mean 82 min). There was no operative mortality or morbidity. Postoperative echocardiography showed no signs of aortic valve regurgation in any patient and continuous wave-Doppler measurements showed that resting pressure gradients across the aortic valve were absent or low. Our preliminary experiences with a stentless aortic xenograft valve show that in presence of an increased cross clamp time an improved hemodynamic function will be obtained. Further studies will be needed, however, to establish the long-term behavior of this device. PMID- 1610598 TI - Gianturco self-expanding metallic stents. PMID- 1610595 TI - Prolonged myocardial protection with St. Thomas' Hospital solution and University of Wisconsin solution. The importance of preservation techniques. AB - The effectiveness of University of Wisconsin solution (UWS) and oxygenated St. Thomas' Hospital solution (STS) for prolonged myocardial protection was evaluated in isolated working rat hearts preserved for 12 h at 4 degrees C using three different preservation techniques: induction of cardiac arrest and subsequent hypothermic storage with STS (group 1, n = 9) or UWS (group 4, n = 9), intermittent coronary flush (every 90 min) with STS (group 2, n = 9) or UWS (group 5, n = 9), or continuous coronary perfusion with STS (group 2, n = 7) or UWS (group 6, n = 7) before 60 min of reperfusion. In the UWS preserved hearts, recovery of aortic flow was greater when the simple storage technique was employed compared to intermittent or continuous coronary perfusion (groups 5 and 6). In the STS preserved hearts, aortic flow recovery was superior when the intermittent perfusion technique was applied. The same pattern was observed with regard to recovery of left ventricular pressure. Lactate dehydrogenase release during reperfusion was significantly less pronounced in group 4 (UWS, single flush, simple storage) as compared to group 1 (STS, single flush and simple storage), whereas best preservation of myocardial high energy phosphates was observed when hearts were preserved with multiple dose cardioplegia using STS. Simple hypothermic storage with UWS affords the best functional recovery after prolonged myocardial ischemia in all groups. Repetitive or continuous application of this solution is detrimental, possibly due to potassium overloading. In STS treated groups, multiple dose application of oxygenated STS enhances functional and metabolic recovery compared to its single dose application.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610599 TI - [Validity of positive anti-Borrelia antibodies in the diagnosis of neuroborreliosis]. PMID- 1610600 TI - [Positive anti-Borrelia antibodies in patients with clinical manifestations compatible with neuroborreliosis]. AB - The clinical features of 19 patients with neurological manifestations unexplained by another disease and positive serology for Borrelia burgdorferi were studied. ECM was present in only 11% of the cases and 32% referred tick bite. The characteristic features for suspicion of NB according to our series was the presence of polyneuritis in 84% of the cases specially in the form of multiple mononeuritis and involvement of the facial nerve (79%) leading to even greater suspicion with the association of V pair involvement. Seizures, sleep disorders, and higher mental dysfunction may be found in association with other more characteristic neurological features. The typical triad of NB (aseptic meningitis, facial paralysis and polyradiculoneuritis) was found in 21% of the patients and in the absence of another disease to justify the same neuroborreliosis (NB) seemed evident. In all the cases components of this triad were found. Headache, arthralgia, fever and, less frequently, arthritis are other symptoms often past with the presence of anti-BB antibodies. Patients with the shortest evolution most frequently presented antecedents of facial paralysis, sensory alterations and Romberg's sign than patients of longer evolution. CSF demonstrated the presence of pleocytosis in 24% of the cases and in only one patient a slight increase in the intrathecal activity of IgG was observed which may be of use in differential diagnosis with MS. MR showed alterations in 61% of the patients and, while not specific, the lesions present subcortical predominance. PMID- 1610601 TI - [Memory changes in Parkinson's disease. Relation with clinical variables]. AB - We studied verbal and visual short term memory, learning capabilities and long term retention in a sample of 96 patients with Parkinson's Disease (PD) and 42 controls matched by sex, age, years of education and verbal intelligence. We found significant differences between groups in visual short term memory and verbal learning, but not in verbal short term memory and long term retention. Performance in visual short term memory and learning correlated with the severity of disease and motor performance. Forty-one per cent of patients had impairment in visual short term memory, and this impairment is related with bradykinesia and correlated with age of onset. These results suggest that two forms of memory failure are closely related to motor symptoms and other clinical variables probably reflecting the same neuropathological substrate. PMID- 1610602 TI - [Neurological manifestations of hyperthyroidism]. PMID- 1610603 TI - [Vertebral hemangioblastoma: an atypical localization]. AB - The case of a 53 year old patient with spastic paraparesis, sphincter function impairment and a deficit of sensation at the T 10 level of 2 months of evolution is presented complementary explorations (simple x-ray of the vertebrae, CT, MR and arteriography) demonstrated the presence of a vascular lesion affecting the 7th thoracic vertebra and which invaded the rachidian channel, compressing the spinal cord. Biopsy study of the intraspinal lesion was diagnosed as hemangioblastoma. A spinal hemangioblastoma with involvement of the vertebra at the same level is reported. The authors present three diagnostic hypothesis: the lesion is a vertebral hemangioblastoma with invasion of the rachidian channel with a evolution similar to vertebral angioma; the lesion is a vertebral angioma which invaded the channel differentiated into hemangioblastoma in its intraspinal position; or it is a spinal hemangioblastoma which has infiltrated the vertebra. PMID- 1610604 TI - [Hypoglycemic hemiparesis]. AB - The common signs of hypoglycemia include: tachycardia, diaphoresis and vertigo which may be associated to disturbances of the consciousness. Occasionally, focal neurological signs occur with conservation of consciousness which are erroneously interpreted as cerebral vascular disease. An insulin dependent diabetic patient is presented with an initial diagnosis of transient ischemic attack (TIA) with right hemiparesis and dysarthria associated to hypoglycemia (35 mg %) whose remission occurred following the correction of glycemia. The different physiopathogenic mechanisms were also revised postulating (selective neuronal vulnerability, vasospasms and subjacent vascular disease) and the need for considering this diagnosis must be emphasized in those diabetic patients with focal neurological symptoms. PMID- 1610605 TI - [Partial complex status epilepticus: presentation of a clinical case]. PMID- 1610606 TI - [Overlapping myasthenic syndrome and thymoma]. PMID- 1610607 TI - [Magnetic resonance and multiple sclerosis]. PMID- 1610608 TI - [Chronic NSAID consumption and ALzheimer's disease]. PMID- 1610609 TI - [Assessment of the degree of severity of mitral regurgitation by the systolic inversion of the pulmonary venous flow. Transesophageal echocardiography study]. AB - It is controversial the value of an echocardiographic mitral regurgitation evaluation based on planimetric patterns color codification area. We made this study using as alternative methods of quantification, the parameter of pulmonary venous flow, concretly maximum velocity and area of pulmonary systolic inversion venous flow. Considered the values of this related parameters to 3 crescent degrees on mitral regurgitation severity and obtained the following results: Lightness mitral insufficiency with maximum inversion area, 10 +/- 21 mm2 and maximum inversion velocity, 3.2 +/- 6 cm/seg. Moderate mitral insufficiency with maximum inversion area, 171 +/- 140 mm2 and maximum moderate velocity, 21 +/- 13 cm/seg. Several mitral insufficiency with maximum inversion area, 648 +/- 615 and maximum inversion velocity, 50 +/- 20 cm/seg. We conclude that systolic parameters of pulmonary venous flow evaluated by transesophagic echocardiography constitute considerable sensibility rules in the evaluation of severity degree in echocardiographic mitral regurgitation. PMID- 1610610 TI - [Assessment of the anti-hypertensive effect of diltiazem in delayed-action capsules by ambulatory monitoring of arterial pressure]. AB - The aim of this parallel controlled-placebo study was to assess the antihypertensive effect of diltiazem in a slow release formulation in monotherapy by the ambulatory blood pressure monitoring (ABPM). Twenty patients with moderate essential hypertension entered the trial. Whole day ambulatory blood pressure (BP) monitoring, with a COLIN ABPM 630, was done after a wash-out period, after placebo administration and 60 days of therapy with diltiazem in a 120 or 180 mg once or twice daily administration. We verified by ABPM that placebo administration did not have an antihypertensive effect (146 +/- 10 mmHg/87 +/- 7 mmHg at base line to 145 +/- 8 mmHg/84 +/- 6 mmHg with placebo p = ns). Eithy four percent of the patients showed a significant systolic and diastolic BP decrease after 60 days of therapy (from 146 +/- 10 mmHg/87 +/- 7 mmHg at base line to 132 +/- 7/77 +/- 6 mmHg - p less than 0.025). In 56% of the patients this was achieved with 180 mg/day and this effect was sustained throughout the 24 hours. We did not find a significant decrease on heart rate. The ABPM is a valuable technique to assess the effect of antihypertensive drugs and demonstrated that diltiazem in a slow release formulation was effective in decreasing systolic and diastolic BP, throughout the day even in patients with low doses, once daily. PMID- 1610611 TI - [Pulmonary stenosis in adults. Report of a clinical case]. AB - The authors report a case of valvular pulmonary stenosis in a 60 years old patient, admitted to hospital with heart failure and angor pectoris. Four years previously a VVI pacemaker had been implanted for complete heart block. At the time of the admission he had two pacemakers leads in the right ventricle; one of them was retained and functionless since the changing of the generator which occurred 1 year before. The usual complications of endocardial pacemakers are discussed, as well as the natural course and surgery indications for valvular pulmonary stenosis in adults. PMID- 1610612 TI - [First Course of cardiovascular clinical pharmacology. II. Adjuvant therapy to thrombolysis. Anticoagulants and platelet aggregation inhibitors]. PMID- 1610613 TI - [Expansion of infarction, dilatation and ventricular remodelling. Therapeutic potential of angiotensin-converting enzyme inhibitors]. AB - Early in the acute phase of myocardial infarction the phenomenon of expansion may occur, with regional thinning and dilatation of necrotic region. This complication may be detected by echocardiography since the first hours of infarction. During the two subsequent weeks, an additional increase of left ventricular volume may occur, due to an increase of length of the infarcted segments and, as well, of the contractile segments which suffer a "volume overload hypertrophy". This is the phenomenon of remodeling. Finally during the first year post infarction, a progressive left ventricular dilatation may develop. This late dilatation seems to be due to an increase of perimeter of the contractile regions only. By the time this topographic changes have occurred, the left ventricle assumes a more spheric configuration. Left ventricular dilatation affects adversely cardiac function, with higher incidences of heart failure and death. Experimental and clinical studies show that, in selected patients, remodeling and ventricular dilatation may be attenuated by the administration of angiotensin-converting-enzyme inhibitors, with better indices of left ventricular function. Final results of several on-going multicenter studies are awaited for; they will allow a better definition of the role of ACE inhibitors on prevention and treatment of left ventricular dysfunction after myocardial infarction. PMID- 1610614 TI - [Clinical trials in cardiovascular clinical pharmacology]. PMID- 1610615 TI - Operational aspects of antibody affinity constants measured by liquid-phase and solid-phase assays. AB - The association constant of monoclonal antibodies (Mabs) to tobacco mosaic virus has been determined in solution and solid-phase binding assays. The ELISA equilibrium titration method developed by Friguet et al. (1985) was found to be suitable for large antigens such as viruses. In the case of intact IgG antibody, it gave equilibrium constant (K) values ca 30% lower than those obtained by classical solution-phase assay while in the case of Fab', the same values were obtained in both assays. Solid-phase binding assays gave higher K values than solution-phase assays by a factor which varied with the Mab tested (1.5- to 5.4 fold higher). Furthermore, in solution-phase assay, K values were found to depend on the antibody concentration used in the assay. These results confirm the operational nature of antibody affinity constants and indicate that in order to compare the affinity of different Mabs in a meaningful way, it is necessary to use a single technique under standardized conditions. PMID- 1610616 TI - Nursing intervention for self-esteem disturbances. AB - In 1988, the broad diagnosis of self-esteem disturbance was refined into three distinct problems: defensive coping, situational low self-esteem, and chronic low self-esteem. The rationale for this refinement is discussed, and distinct nursing interventions are proposed that differ by type of self-esteem problem and nursing expertise. PMID- 1610617 TI - Inadvertent hypothermia: clinical validation in postanesthesia patients. AB - The nursing diagnosis of hypothermia contains a variety of defining characteristics and an inconsistency in an exact temperature measurement for this diagnosis. A review of the literature from surgery, anesthesiology, and physiology identified criteria for three types of hypothermia: inadvertent, accidental, and intentional. In addition to the three types, three different core temperatures were given to facilitate medical diagnosis of these types. This study examines inadvertent hypothermia in postanesthesia patients. The findings indicated that inadvertent hypothermia characteristics are distinctly different from the global nursing diagnosis of hypothermia. Future studies are recommended to confirm the findings from this study and to validate accidental and intentional types of hypothermia. PMID- 1610618 TI - Development of definitions for taxonomy II. AB - In the process of placing diagnoses into Taxonomy I, certain inconsistencies became apparent. Inadequate definition of both diagnoses and human response patterns, lack of defining characteristics, and inconsistency in the levels of abstraction within the taxonomic hierarchy made the task of assigning a diagnosis to a taxonomic pattern difficult. Ambiguity in the definitions of the nine patterns resulted in ambiguity in the basic foundation, which affected the entire structure. The Taxonomy Committee, before evaluating the current structure, had to make the following decisions regarding the current human response patterns: (1) Should the nine human response patterns be retained for further taxonomic work? and (2) If they are retained, what should be the first step in examining Taxonomy I-Revised? This second article in a series of four will familiarize the readers with the process and decisions by which Taxonomy II of the North American Nursing Diagnosis Association (NANDA) is evolving through the work of the Taxonomy Committee. This article also will identify the specific problems encountered in the development of Taxonomy I and Taxonomy I-Revised, and describe the steps establishing the validity of the process of formation of the nine human response patterns. PMID- 1610619 TI - A synthesis of selected literature on mobility: a basis for studying impaired mobility. AB - The concept of mobility can be found in the nursing diagnosis literature as impaired physical mobility, which is generally defined as limitations of physical movement within the environment. In this context, mobility is viewed within the confines of the physical realm. This conceptualization is restrictive in scope and therefore does not provide much direction for the nurse clinician. The theoretical basis of mobility must be strengthened to generate the knowledge necessary to understand impaired physical mobility. The purpose of this article is to present a consolidated review of the literature related to the concept of mobility. Studies from the social sciences are explored. Conceptual orientations from the health literature also are discussed. Finally, the nursing perspective is examined, including the measurement of the concept. PMID- 1610620 TI - Mental status and functional abilities: change in institutionalized elderly women. AB - A study of 40 institutionalized elderly women was undertaken to determine if changes occurred in mental status and functional abilities over the course of 1 year. Although a number of studies examine factors that impact on successful adaptation in persons admitted to long-term care facilities, the longitudinal changes on functional abilities and mental status have not been addressed. These variables were examined in relation to the concept of self-care, which has been applied to the elderly only recently. Findings indicate a decline in mental status and an increase in functional dependency. Nursing implications and questions that merit further study in the area of self-care are presented. PMID- 1610621 TI - Collaboration revisited. PMID- 1610622 TI - Custom selection of support surfaces for wheelchairs and beds: one size does not fit all. AB - Support surfaces aid in preventing pressure sores and trauma, correct posture, and provide patient comfort. Knowing how to custom select a support surface is vital for meeting the patient's protective, postural, and pain-prevention needs. PMID- 1610624 TI - What's your assessment? Pityriasis rosea. AB - As a nurse practitioner in dermatology for over 15 years, Barbara Bielan has been fortunate to have worked with many superb clinicians who have shared their time and expertise in giving her a broad background in dermatology. The "What's Your Assessment?" series includes a short case presentation and differential diagnosis. It is followed by a discussion on the disease and the rationale used in each step of the assessment. PMID- 1610623 TI - Case study: enhancing compliance in an adolescent with atopic dermatitis. AB - Compliance in the adolescent with atopic dermatitis can be a challenge to the dermatology nurse. Compliance can be enhanced through education and followup with the patient, his/her family, school, and other health care professionals. PMID- 1610625 TI - Facial moisturizers and wrinkles. AB - Facial moisturizers are part of the cosmetic category known as skin care products, which also includes other facial products such as astringents, toners, soaps, and bath products. This article describes the composition and pharmaceutics of currently marketed moisturizers, the use of fragrances and preservatives in these products, how cosmetic facial moisturizers work on wrinkles, sunscreen-containing facial moisturizers, and the Food and Drug Administration's record regulating drug claims for anti-wrinkling products. PMID- 1610626 TI - A new four-parameter threshold model for the plasma atracurium concentration response relationship. AB - The plasma concentration of atracurium and the electromyographic depression of the first response of the train-of-four (T1:T0) were measured during and after recovery from a 10-min infusion of atracurium 0.25 mg kg-1 in 14 patients anaesthetized with 66% nitrous oxide and 0.9% isoflurane (end-tidal) in oxygen. A standard pharmaco-dynamic model was fitted to the data; a small but consistent discrepancy was found between the time and rate of onset of depression of the ratio T1:T0 and the predictions of the standard biophase model of best fit to the data. This discrepancy is reduced by the inclusion of a threshold term (CPss theta) in the model to represent the greatest steady state plasma concentration which would just fail to evoke an effect. The values of CPss theta correlated significantly with the values of CPss50 (r = +0.627; P less than 0.02). The estimates of CPss50 and keo from the two models are very similar; the estimate of gamma, the slope of the concentration-response curve, was less in the threshold model. The relationship of the present threshold model to existing knowledge of neuromuscular physiology is discussed. PMID- 1610627 TI - Dependence of the neuromuscular blocking effect of atracurium upon its disposition. AB - We have assessed the profiles of plasma concentration of atracurium and its neuromuscular blocking effect on the first response of the train-of-four measured by electromyography after a short infusion of atracurium 0.25 mg kg-1, in 38 patients anaesthetized by one of three techniques. Measures of the temporal profile of neuromuscular block were found to correlate with pharmacokinetic variables. When anaesthetic technique was taken into account in a multivariate model, the time to onset of 10% deprssion of T1:T0 correlated positively with the central volume of distribution (P less than 0.05). The change in T1:T0 during the 1 min after 10% depression, and the logit of maximum depression were both correlated negatively with the central volume of distribution (P less than 0.05 and P less than 0.01, respectively). Both the times to 20% and 50% recovery of T1:T0 correlated strongly negatively with clearance (P less than 0.0001 for both measures). The findings support the conclusion that the effect of atracurium is dependent upon its disposition. PMID- 1610628 TI - Halothane does not depress contractile function of fresh or fatigued diaphragm in pentobarbitone-anaesthetized dogs. AB - We have studied the effect of halothane on diaphragmatic contractile function by measuring transdiaphragmatic pressure (Pdi) and electromyogram of the diaphragm (Edi) during various stimulation frequencies in 15 pentobarbitone-anaesthetized dogs undergoing mechanical ventilation. We have examined also the effect of halothane on the fatigued diaphragm by repeating the measurements 5, 10, 15, 30, 60 and 90 min after 30 min of tetanic stimulation applied to the phrenic nerves. Administration of 1-2 MAC of halothane did not affect Pdi at any given stimulation frequency. Changes in the depth of halothane anaesthesia (0, 1 and 2 MAC) did not alter the force-frequency relationship of the diaphragm during recovery from fatigue. Edi was unaffected by halothane, except for a small decline during 100-Hz stimulation with 2 MAC. In contrast with the changes in Pdi, Edi during recovery from fatigue was the same as that determined before fatigue. It is concluded that halothane, in clinical concentrations, did not depress the contractile function of fresh or fatigued diaphragm in vivo. PMID- 1610629 TI - Neuromuscular blocking activity of tubocurarine in patients with diabetes mellitus. AB - Previous clinical reports have suggested that deep tendon reflexes of diabetic patients are delayed and experimental studies have reported differential sensitivity of motor endplates to neuromuscular blocking drugs. These observations prompted us to study the neuromuscular effect of tubocurarine in 25 diabetic and 15 non-diabetic patients during urological surgery. Anaesthesia was induced with thiopentone followed by suxamethonium and maintained with nitrous oxide in oxygen and increments of butorphanol. Muscle relaxation was provided with tubocurarine in an initial dose of 0.25 mg kg-1 and increments of 20% of the initial dose. At the end of surgery, residual neuromuscular block was antagonized with increments of neostigmine 0.5 mg and atropine 0.2 mg. There was a delay in the onset of action of tubocurarine in diabetic patients. A no-response state was obtained in some patients, and its duration correlated with post-tetanic count (PTC) in diabetic patients, and with post-tetanic twitch height percent (PTTH%) in the control group. We concluded that, in diabetic patients, the onset of action of tubocurarine was delayed compared with control patients, and the reliable predictor of the duration of the no-response time was PTC in diabetic patients and PTTH% in non-diabetic subjects. PMID- 1610630 TI - IV fluids and minor gynaecological surgery: effect on recovery from anaesthesia. AB - This study has examined the effect of hydration on immediate recovery from anaesthesia in two groups of 15 patients undergoing therapeutic abortion. A standard anaesthetic technique was administered. Patients in group I received no preoperative fluid; those in group II received, before anaesthesia, 20 ml kg-1 of 4% glucose and 0.18% saline. Recovery was assessed using two tests of psychomotor function: a reaction time test and a letter cancellation task. Subjective symptoms were assessed with a questionnaire. There was a significant decrease in reaction time after operation (both motor and reaction times) in group I (no fluids), but not in group II (fluids). There were no significant between-group differences in objective tests or subjective measures. Thus we could not demonstrate any obvious benefit of i.v. fluid administration. Approximately 500 patients would be required to have an 80% chance of establishing a statistically significant between group difference. PMID- 1610631 TI - Continuous extradural analgesia: comparison of midwife top-ups, continuous infusions and patient controlled administration. AB - We have compared three techniques used to provide extradural analgesia during the first stage of labour: 0.25% plain bupivacaine 10 ml demand top-ups delivered by the midwife; continuous infusion of 0.125% plain bupivacaine 10 ml h-1; and patient-controlled extradural analgesia (PCEA) delivering 3-ml boluses of 0.25% bupivacaine. Each technique produced comparable analgesia achieving equivalent maternal satisfaction, with no difference in mode of delivery and no complications. This regimen for PCEA proved a viable alternative for continuous extradural analgesia and was popular with the mothers, midwives and anaesthetists. PMID- 1610632 TI - Cardiovascular support during combined extradural and general anaesthesia. AB - We have examined the effect of prophylactic treatment with i.v. fluid 1000 ml, ephedrine 24 mg or methoxamine 4 mg on cardiovascular responses to both extradural and combined extradural and general isoflurane anaesthesia in 45 adult patients undergoing knee arthroplasty. Heart rate (HR) and systemic arterial pressure (AP) were measured using automated oscillotonometry and cardiac output was measured using continuous wave suprasternal Doppler ultrasonography. After lumbar extradural anaesthesia (LEA) there were no significant differences in arterial pressure between treatments, although cardiac index was significantly greater after fluid preloading (mean 4.3 (95% confidence interval 3.7-4.9) litre min-1 m-2) than after ephedrine (3.1 (2.6-3.6) litre min-1 m-2) or methoxamine (2.6 (2.0-3.2) litre min-1 m-2). During combined LEA and general anaesthesia, systolic AP was significantly greater after ephedrine (114 (103-125) mm Hg) than after either preloading (98 (88-107) mm Hg) or methoxamine (97 (89-105) mm Hg). The reduction in AP after induction of general anaesthesia was associated with a decrease in cardiac index after fluid preloading and a decrease in vascular resistance after methoxamine. PMID- 1610633 TI - Spinal anaesthesia for caesarean section: 0.125% plain bupivacaine 12 ml compared with 0.5% plain bupivacaine 3 ml. AB - Forty women had elective Caesarean section under spinal anaesthesia with either 0.5% bupivacaine 3 ml or 0.125% bupivacaine 12 ml, injected at a rate of 1 ml/5 s. For 30 min after the spinal injection, each patient lay on her right side. Compared with the patients given 3 ml, in those given bupivacaine 12 ml there was a significantly greater spread of block (P less than 0.02 for analgesia; P less than 0.002 for touch) and significantly less variation in levels of block (P less than 0.02 for analgesia; P less than 0.04 for touch). However, within 5 min of placing the women in a supine, tilted (right hip up) position, there were no clinically or statistically significant differences in the levels of block between the two groups. PMID- 1610634 TI - Plasma concentrations of lignocaine after obturator nerve block combined with spinal anaesthesia in patients undergoing transurethral resection procedures. AB - Bilateral obturator nerve block has become a widely accepted technique to avoid adductor contraction during transurethral resection of prostate or bladder tumours. However, little is known about plasma lignocaine concentrations after the block. We conducted this study to assess a safe dose of lignocaine for injection in obturator nerve block. Bilateral obturator nerve block was performed with the aid of a peripheral nerve stimulator in 12 patients after spinal anaesthesia. In group I (n = 6), patients received 2% lignocaine 10 ml (200 mg) for the block; those in group II (n = 6) received 2% lignocaine 15 ml (300 mg). The block was satisfactory and no single adductor contraction was observed in either group during surgery. The peak plasma concentrations of lignocaine were 2.28 (SD 0.29) micrograms ml-1 and 3.75 (0.79) micrograms ml-1 in groups I and II, respectively. The greatest plasma concentration was 5.07 micrograms ml-1 in a patient of group II. There were no symptoms suggesting systemic toxicity. We conclude that bilateral obturator nerve block may be performed safely and effectively with 2% lignocaine 10 ml with the aid of a peripheral nerve stimulator in patients undergoing transurethral resection procedures with spinal anaesthesia. PMID- 1610635 TI - Inspiratory to end-tidal oxygen difference during nitrous oxide anaesthesia. AB - In order to evaluate the value of the inspiratory to end-tidal oxygen concentration difference (Io2-E'o2) as a monitor during general anaesthesia, we studied 40 orthopaedic patients allocated randomly to four groups: anaesthesia with enflurane or isoflurane in nitrous oxide with either spontaneous or controlled ventilation. (Io2-E'o2) followed an asymptotically increasing curve because of decreasing uptake of nitrous oxide. At 1 h, (Io2-E'o2) approached the end-tidal carbon dioxide concentration (E'o2). During spontaneous ventilation, (Io2-E'o2) correlated best with E'co2. During controlled ventilation, there was a negative correlation between (Io2-E'o2) and nitrous oxide uptake rate. Changes in oxygen uptake rate were reflected in (Io2-E'o2), provided that the total ventilation volume was constant and the nitrous oxide uptake rate approached steady state conditions. PMID- 1610636 TI - A model lung with direct representation of respiratory muscle activity. AB - We describe the theory, construction and testing of an active model lung. This is designed so that when it is connected to a ventilator, the interaction between spontaneous ventilatory activity in the patient and the pressures and flows generated by the ventilator are reproduced faithfully. A waveform of negative pressure, pmus, equivalent to the action of the respiratory muscles, is applied indirectly to the compliance unit of a conventional model lung. It is shown that, when the compliance and resistance of a subject have been measured, the waveform of pmus can be determined. This was undertaken in three volunteers breathing under various conditions, including connection to a ventilator operating in different modes. When these conditions were reproduced with the lung model replacing, but matched to, each subject, the original waveforms of flow and pressure at the mouth were reproduced. PMID- 1610637 TI - Effect of pethidine premedication and halothane anaesthesia on upper limb blood flow. AB - Forearm blood flow (FBF), hand blood flow (HBF) and arterial pressure were measured in 12 patients, before and after premedication with pethidine and during halothane anaesthesia. After pethidine there was a significant (P less than 0.01) increase in HBF (180%) and decreased hand vascular resistance; heart rate also increased significantly (P less than 0.05), whilst mean arterial pressure (MAP) did not change. The large increase in HBF without hypotension suggests a local effect. With halothane, there was a significant (P less than 0.05) decrease in MAP, increase in HBF and decrease in hand vascular resistance compared with either control or effects produced by pethidine; there was a significant decrease in FBF and reversal of the action of pethidine on forearm vascular resistance. PMID- 1610638 TI - Severe hypertension during postpartum haemorrhage after i.v. administration of prostaglandin E2. AB - Severe hypertension with arterial spasm was observed after i.v. administration of prostaglandin E2 (PGE2) during uterine exploration under general anaesthesia for control of postpartum haemorrhage. This hypertension was exceptional because PGE2 is known to cause a decrease in systemic arterial pressure. Different hypotheses for this paradoxical hypertensive crisis after PGE2 administration are discussed. PMID- 1610639 TI - Nitrous oxide administration using commonly available oxygen therapy devices. AB - Administration of nitrous oxide is useful for providing sedation and analgesia. The therapeutic range for nitrous oxide is 20-30%. Several oxygen treatment devices have been used for administering nitrous oxide, but little is known about the concentrations of nitrous oxide and oxygen delivered to the trachea. We have studied this, using an analogue lung model, with several oxygen therapy devices. With a 1:1 nitrous oxide-oxygen mixture in the primary flow for all systems, end expired nitrous oxide concentrations varied between 6.5% and 34.3%. Therapeutic concentrations were produced using the Hudson (nominal oxygen concentration 60%) fixed-performance mask, the variable performance Hudson mask at 4 litre min-1, the MC masks at 4 and 6 litre min-1 and the nasal prongs at 6 and 8 litre min-1. Simultaneous end-expired oxygen concentrations for all devices tested were within a safe range. PMID- 1610640 TI - Acupuncture and postoperative vomiting in children. PMID- 1610641 TI - Acupuncture and postoperative vomiting in children. PMID- 1610642 TI - Acupressure and postoperative vomiting in strabismus correction. PMID- 1610643 TI - Combined spinal-extradural anaesthesia in obstetrics. PMID- 1610644 TI - Use of drugs in children. PMID- 1610645 TI - Maternal and fetal haemodynamic effects of spinal and extradural anaesthesia for elective caesarean section. PMID- 1610646 TI - Prediction of the spread of repeated spinal anaesthesia with bupivacaine. PMID- 1610647 TI - Adequacy of preoperative safety checks of the Bain breathing system. PMID- 1610648 TI - Postdural puncture headache. PMID- 1610649 TI - Fibromuscular disease of the external iliac artery. AB - Fibromuscular disease is rarely observed in the external iliac artery. During the last 15 years, eight symptomatic cases were encountered in six women and two men whose ages ranged from 29 to 63 years (mean: 47 years). Clinical onset was always recent, either progressive with claudication (three cases) or sudden with abdominal and pelvic pain and acute ischemia due to dissection (five cases). Diagnosis was established by arteriograms showing either a typical appearance of fibromuscular hyperplasia or a segmental dissection or occlusion. Two patients had associated fibromuscular disease of the renal arteries. One of these patients had dysplastic aneurysm of the thyrocervical trunk. Histopathological findings were typical of medial fibromuscular hyperplasia in the seven cases examined. Even though transluminal dilatation is presently simple, adequate, and durable for the management of non-complicated forms, all of our cases were treated surgically either because they were observed before transluminal dilatation was readily available or because of associated dissection. Results of surgery were satisfactory in all cases except one with a mean follow-up of 12.6 years. One patient was reoperated upon 13 years later. PMID- 1610651 TI - Unilateral iliac artery occlusive disease: a randomized multicenter trial examining direct revascularization versus crossover bypass. Association Universitaire de Recherche en Chirurgie. AB - This randomized trial compared the patency of direct unilateral aorto- or iliofemoral prosthetic bypass with that of crossover femorofemoral or iliofemoral bypass in unilateral atheromatous occlusive disease of the iliac artery. Between May 1986 and March 1991, 143 patients were enrolled in this study (74 crossover and 69 direct revascularizations). Cardiovascular risk factors, preoperative symptoms, and atheromatous lesions were similar in both groups. Patients were followed by Duplex scanning with systolic pressure index measurements. Routine digital subtraction arteriograms were obtained postoperatively and separately, when hemodynamic anomalies developed. Mean follow-up was 22 months. One patient with direct revascularization died postoperatively. Primary patency of direct revascularizations was 89.8% at 48 months compared with 52% for crossover bypass. This difference was statistically significant. Secondary patency of direct and crossover revascularization at 48 months was 92.9% and 93.6%, respectively (not significant). Even though crossover bypasses seem attractive because of their technical simplicity and low morbidity, our results suggest that direct revascularizations are preferable in the young patient with no major operative risks, while crossover bypasses remain indicated in patients at risk. PMID- 1610650 TI - Aneurysms of the extracranial internal carotid artery due to fibromuscular dysplasia: results of surgical management. AB - Between January 1977 and December 1990, eight patients underwent surgical correction of aneurysms of the extracranial internal carotid artery due to fibromuscular dysplasia. Mean age of patients was 50 years (range 31 to 70 years). Five patients presented with neurologic hemispheric symptoms. Most aneurysms were saccular and occurred preferentially at the level of C2 or C3. All of these patients underwent operation through conventional cervicotomy. Resection anastomosis was performed in three cases whereas resection-graft was performed in five. Histopathological examination of the eight specimens was consistent with fibromuscular dysplasia of the media. There was no central nervous system-related mortality and morbidity. Seven patients were alive and free of new neurological manifestations at mean follow-up of 156 months (18 to 180 months). One patient died of myocardial infarction at 96 months. All patients had postoperative duplex scanning or arteriograms. These revealed that carotid restorations were patent in seven whereas one patient had asymptomatic occlusion at 18 months. PMID- 1610652 TI - Fibromuscular disease of the renal artery: a new histopathologic classification. AB - To evaluate the relationship between clinical, radiologic, and histopathologic features in various types of renal artery fibromuscular disease, the records of 37 patients operated upon for a total of 44 lesions of the renal artery (30 unilateral and seven bilateral) were retrospectively reviewed. Of these, 36 had hypertension associated with stenosis or aneurysm of the trunk or branches of the renal artery; one had aneurysm of the renal artery without hypertension. The histopathologic study included 38 arterial segments retrieved from 33 patients and underscored the difficulties in using topographic criteria to classify lesions. While all arterial aneurysms were associated with involvement of the media, more than one layer of the artery was involved in 65.7% of cases. Topographic forms, such as the perimedial type, were difficult to classify. Based on the study results, it appears essential to distinguish patients with fibrosis and smooth muscular hyperplasia (type I: 19 patients, 23 arteries) from patients with isolated fibrosis (type II: 14 patients, 15 arteries). In group II, preoperative hypertension was more long-standing (p less than 0.04), more lesions were extended distally (p less than 0.05), and the probability of recovery from hypertension at 52 months follow-up was lower. We have distinguished two different evolutive stages of fibromuscular disease of the renal artery, one characterized by fibrosis with smooth muscle hyperplasia and the second, associated with more severe prognosis, characterized by isolated fibrosis. PMID- 1610653 TI - Dysplastic lesions of renal artery branches: late results of ex vivo repair. AB - Between November 1980 and July 1989, 29 ex vivo reconstructions were performed in 12 women and five men (mean age: 42 years) for dysplastic lesions of renal artery branches. Fifteen patients had hypertension, associated with advanced renal failure in one case. The internal iliac artery was used routinely for reconstruction. The saphenous vein was used on one side where bilateral repairs were necessary. A total of 52 distal anastomoses were performed, an average of 2.6 per revascularized kidney. Mean follow-up was four years and 10 months. No patients were lost to follow-up. There were no early or late deaths. At least one follow-up arteriogram and technetium99 diethylene triamine pentacetic acid scintiscan was obtained for all patients. Forty-five (86%) of 52 anastomoses remained patent. Eleven of 15 hypertensive patients completely recovered while four were improved. Systolic arterial blood pressure decreased by an average of 42 mmHg (p less than 0.001), and results remained stable with time. For fibromuscular dysplasia occurring in young patients whose life expectancy is usually long, this type of surgery provides excellent long-term clinical and anatomical results. PMID- 1610654 TI - Simultaneous reconstruction of infrarenal abdominal aorta and renal arteries. AB - From 1980 to 1990, 48 (4.7%) of 1,002 patients underwent elective aortic reconstruction and simultaneous renal artery reconstruction. Forty-five men and three women (mean age: 66.5 years) had 59 renal artery lesions (51 stenoses, six occlusions, one dysplasia, and one aneurysm) associated with 20 infrarenal aortic aneurysms and 28 aortoiliac occlusive lesions. One nephrectomy and 58 renal artery reconstructions were performed (35 prosthetic bypasses, 11 vein bypasses, six direct reimplantations, five transaortic endarterectomies, and one resection of an intrahilar aneurysm followed by autotransplantation). Operation was always indicated for the aortic lesions. Indication for renal artery repair was hypertension in 33 cases (17 associated with renal insufficiency) and one with isolated renal insufficiency. In the remaining 14 cases, surgery was deemed preventive. One patient died (2%). There were 12 nonfatal complications two of which were kidney failures requiring chronic extrarenal epuration. Routine follow up arteriograms showed four postoperative renal artery occlusions. Mean follow-up was 35.8 months. Four patients were lost to follow-up; 10 died secondarily. Five year survival was 72.1 +/- 19.1%. Secondary patency of renal artery reconstruction was 89.5 +/- 9.4% at five years. Late results were favorable in 45% of patients with hypertension and in 39% of patients with renal insufficiency. Mortality in simultaneous aortic and renal artery reconstruction is not superior to that of isolated infrarenal aortic surgery. PMID- 1610655 TI - Human immunodeficiency virus and infected aneurysm of the abdominal aorta: report of three cases. AB - Three patients who were seropositive for human immunodeficiency virus underwent surgery for infected aneurysm of the abdominal aorta. Fever and abdominal pain were the principal presenting clinical features. None of the patients had any opportunistic infections or endocarditis. In two cases, a ruptured aneurysm was demonstrated radiographically. In the remaining case, sonograms were diagnostic. The organisms responsible were salmonella, Hemophilus influenzae, and Mycobacterium tuberculosis. In two cases, the infectious origin was evidenced by bacteriologic examination of the aortic wall, which revealed the presence of Salmonella enteritidis and Koch's bacillus. Although Hemophilus influenzae was not found in the aortic wall of the remaining case, the infectious origin of the aneurysm was established because preoperative blood cultures were positive for this pathogen, and pathohistologic examination of the specimen showed destruction associated with leukocyte infiltration of the aneurysmal wall. An in situ prosthetic graft replacement protected by omentum was performed in all three cases. Antibiotic therapy was continued for several weeks. All patients are well with follow-up ranging from 10 to 21 months. Infectious aneurysm associated with human immunodeficiency virus seropositivity results in bacterial infestation of an atheromatous aorta. Infected phenomena are promoted by cellular immunodeficiency. Surgery was justified in these cases because of the immediate threat of rupture. PMID- 1610656 TI - Bilateral severe carotid stenosis or occlusion and computed tomographic scan positive hemispheric stroke with neurologic deficit: immediate contralateral carotid endarterectomy. AB - In the last 10 years, 13 patients presented with acute, hemispheric, computed tomographic scan-positive stroke; neurologic deficit; and bilateral carotid stenosis greater than 90% (N = 9) or ipsilateral occlusion with contralateral stenosis greater than 90% (N = 4). To improve ipsilateral flow without elevation of pressure to levels causing hemorrhagic infarction, all patients underwent carotid endarterectomy on the side contralateral to the hemispheric stroke from two to 10 days (average 6.6 days) from onset of symptoms. Those with fluctuating deficits stabilized to the initial fixed deficit and all 13 improved over the next six months. Four patients with ipsilateral internal carotid occlusion and one with ipsilateral severe siphon stenosis were discharged on antiplatelet therapy; of the remaining eight patients, seven underwent subsequent ipsilateral carotid endarterectomy from 42 to 111 days (average 58.4 days) from onset of symptoms. Mortality and stroke rate were 0. The four patients with internal carotid occlusion and the one with severe siphon stenosis filled both hemispheres from the contralateral carotid artery arteriographically in four and by oculoplethysmography in one. One patient demonstrated preferential flow from contralateral to the ipsilateral hemisphere, but not the reverse; one patient demonstrated pericallosal collaterals. Immediate endarterectomy of the severely diseased carotid artery contralateral to a hemisphere with a computed tomographic scan-positive stroke causing neurologic deficit resulting from a severe carotid stenosis is a safe treatment option and may be beneficial in those with fluctuating neurologic deficits. PMID- 1610657 TI - Optimal seeding conditions for human endothelial cells. AB - An in vitro model of endothelial cell seeding has been developed to individually evaluate the steps required for seeding arterial prostheses. Human saphenous vein endothelial cells are radiolabeled with tritiated thymidine and seeded onto 4 mm polytetrafluoroethylene grafts. Grafts are then placed into a perfusion circuit for determination of cellular retention. Using this model, the following variables were studied: (1) graft coating (fibronectin versus serum versus plasma); (2) time of incubation of cells with graft (0, 20, 90 minutes); (3) density of the initial seeding solution (4 x 10(3)-6 x 10(5) cells/cm2). The data suggest that incubation of a graft with plasma provides an adhesive surface that is as effective as fibronectin for enhancing cell retention. With this particular model, seeding densities between 1 and 2 x 10(5) cells/cm2 produce a confluent monolayer with optimal utilization of cells. A shorter 20 minute incubation period resulted in the retention of only half of the seeded cells, while postperfusion attachment increased significantly with a 90 minute incubation period. Data derived from this system can be used to construct a protocol that may be useful for clinical in vivo seeding trials. PMID- 1610658 TI - Antiproliferative effect of heparin on human smooth muscle cells cultured from intimal hyperplastic lesions of vein grafts. AB - The antiproliferative effect of heparin on cultured smooth muscle cells in proliferating human smooth muscle cells derived from clinical lesions of intimal hyperplasia was tested. Smooth muscle cells were obtained from stenotic segments excised from failing in situ saphenous vein bypass grafts in three patients. The nonadventitial portion of the excised tissue was explanted into cell culture using standard techniques without the addition of exogenous growth factors. Under these conditions, rapid cell outgrowth was observed from these explants, in contrast to minimal growth of smooth muscle cells from normal veins from the same patients. Immunohistochemical staining with antiactin antibody confirmed that the cells cultured from the stenotic lesions were smooth muscle cells. Incubation of these cells with porcine mucosal heparin revealed a significant (p less than .01) dose-dependent inhibition of cell proliferation as measured by radioactive thymidine incorporation. Mean inhibition of six subcultures tested ranged from 3 to 46%, at heparin concentrations of 1 to 1,000 micrograms/ml. The magnitude of heparin's antiproliferative effect varied among the cell lines from different patients, but 10-30% inhibition was consistently observed at heparin concentrations usually attained in vivo. The maximal inhibition achieved was 65% in one cell line at the highest heparin dose. We conclude that heparin exerts a significant antiproliferative effect on human smooth muscle cells cultured from intimal hyperplastic lesions from in situ saphenous vein bypass grafts. PMID- 1610659 TI - Intraoperative peripheral rotary atherectomy: early and late clinical results. AB - Early and late clinical results of intraoperative peripheral atherectomy using the Auth Rotablator are analyzed. Twenty patients (15 males and 5 females age 39 89 years, mean 70 years) underwent 25 atherectomy procedures for peripheral arterial occlusive disease from August 1987 to October 1989. All patients underwent serial history, physical exam, and Doppler pressure measurements preoperatively and then postoperatively at 24 hours, one week, one month, and six months during a follow-up period of 15 to 41 months, mean 27 months. Preoperative and intraoperative completion follow-up arteriography was done in all cases and follow-up arteriography in 19 of 25 cases. Initial arteriographic success was achieved in 23/25 (92%) cases and in 39/41 (93%) arterial segments (superficial femoral artery 12/13, popliteal 14/15, tibial 12/13, profunda-femoral 1/1). Complications included intimal dissection (1), equipment breakage (2), minor emboli (3), major emboli with thigh skin loss (1), transient hemoglobinuria (4), wound hematoma (1), wound infection (1), and limb loss (1). Early thrombosis occurred in five cases to give an in-hospital success rate of 18/25 (72%). Primary patency was 66% at six months but only 12% at two years. Rotary atherectomy effectively recanalizes femoral, popliteal and tibial arteries. However, early thromboembolic complications occurred frequently, and the two year patency was dismal. Rotary atherectomy is not recommended for general use until problems of thromboemboli and intimal hyperplasia are solved. PMID- 1610660 TI - Amaurosis fugax: is it innocuous? AB - A 10 year retrospective study of 103 patients with amaurosis fugax was done. Sixty-two patients with symptoms of amaurosis fugax underwent arteriography, which demonstrated ulcerated carotid plaque in 36 and hemodynamically significant stenoses (greater than 75% diameter reduction) in 26. These 62 patients underwent carotid endarterectomy. The other 41 patients who had proven ulcerated plaque (33 patients) or hemodynamic stenoses (eight patients) were not treated surgically and served as a control series. No strokes or deaths occurred in the immediate postoperative period. Follow-up of the 62 operated patients extending to 10 years (mean 4.2 years), revealed one (1.6%) patient with recurrent amaurosis fugax symptoms, two (3.2%) with transient ischemic attacks, and one (1.6%) with a stroke in the operated hemisphere. In the nonoperated group, despite aspirin or warfarin treatment, four (9.7%) patients had ongoing amaurosis fugax symptoms, and two (4.8%) developed transient ischemic attacks that led to carotid endarterectomy. One (2.4%) other patient developed sudden, permanent monocular blindness, and two (4.8%) suffered hemispheric strokes, one of which was fatal. The cumulative morbidity (ongoing ocular or transient ischemic attack symptoms, perioperative and late stroke) in the operated group was 6.4% (four patients), while the cumulative morbidity in the nonoperated group was significantly higher at 21.9% (nine patients) (p = 0.02). When patients present with symptoms of amaurosis fugax and have demonstrable carotid bifurcation disease, carotid endarterectomy is recommended. Amaurosis fugax should be regarded as a harbinger of monocular blindness and stroke. PMID- 1610661 TI - Aneurysm of lateral circumflex femoral artery in association with multiple atherosclerotic aneurysms. AB - Femoral aneurysms are uncommon and are frequently associated with other aneurysms, particularly those of the aorta and popliteal arteries. Other peripheral aneurysms are even more rare. As far as we are aware, only one aneurysm of the lateral circumflex artery has been previously described. We describe such an aneurysm in association with a common femoral aneurysm on the same side, an abdominal aortic aneurysm and an iliac aneurysm on the contralateral side. PMID- 1610662 TI - Cervical rib variant: report of a case. AB - It is taught that, when a cervical rib is present, the subclavian vessels and brachial plexus always arch over it. The present case reemphasizes that the brachial plexus may be split by the cervical rib. PMID- 1610664 TI - Pathogenesis of acquired aneurysms of the abdominal aorta. AB - The incidence of abdominal aortic aneurysm has recently increased. There is still no accurate definition of abdominal aortic aneurysm. The diameter of abdominal aortic aneurysms is the only factor permitting evaluation of the risk of rupture of aneurysms whose growth remains unpredictable. Abdominal aortic aneurysm is a multi-factorial disease associated with aortic aging and atheroma. It differs from stenotic disease by the intensity of degenerative or destructive phenomena in the media. Particular hemodynamic conditions in the infrarenal abdominal aorta seem to enhance the development of aneurysm at this level. While certain constitutional anomalies of the extracellular matrix of proteins seem to enhance the development of abdominal aortic aneurysm, protease activity of as yet undetermined origin also seems to play a prominent role. Family cases of abdominal aortic aneurysms have been reported but the mechanisms responsible remain to be determined. Several genetic markers have been suggested. The most reliable marker of aortic aneurysm is arteriomegaly. PMID- 1610663 TI - Vascular manifestations in homocystinuria. AB - Homocystinuria was discovered in a 21-year-old woman when she presented with lower limb ischemia and pulmonary embolism. This patient had a partial deficit in cystathionine-synthetase and took strongly dosed oral contraceptive medication. This report underscores: (1) the value of searching for this type of pathology even in the adult; (2) the possibility of disclosure by another condition, and particularly, drug-induced; (3) the importance of searching for other involved members of the same family; and (4) the possibility of treatment in vitamin sensitive patients. PMID- 1610665 TI - Management of juxtarenal aortic occlusions: technique for suprarenal clamp placement. AB - Atherosclerotic occlusion of the entire infrarenal abdominal aorta can produce gangrene, rest pain or claudication and can progress to involve the renal artery origins. Features of the operative technique for treating these juxtarenal aortic occlusions include self-retaining retraction, mobilization of the left renal vein with division of all non-renal branches, exposure of the suprarenal aorta and renal arteries by division between clamps of the surrounding paraaortic fibroareolar tissue and fat, sharp division of crural attachments to the aorta, control of the two renal arteries with doubled vessel loops and then direct vertical clamping of the suprarenal aorta. Through an arteriotomy below the renal arteries, 2-4 cm of pararenal aorta are cleared of thrombus and atherosclerotic debris under direct vision. After transfer of the suprarenal clamp to an infrarenal position, conventional aortobifemoral bypass is then performed. In a series of 18 patients with juxtarenal aortic occlusion managed by this technique, suprarenal clamp time ranged from 4 to 25 minutes (mean, 13 minutes). There was no morbidity from renal failure or emboli and no mortality. This technique allows for deliberate, careful disobliteration of the pararenal and infrarenal aorta and minimizes the risk of renal embolization. PMID- 1610666 TI - Hypercoagulability in vascular surgery patients. PMID- 1610667 TI - Global programme on AIDS. Consensus statement from the WHO/UNICEF consultation on HIV transmission and breast-feeding. PMID- 1610668 TI - Decreasing the risk of exposure to blood. PMID- 1610669 TI - Progression of HIV infection in drug users. PMID- 1610670 TI - Nursing abroad: heading for the United States? PMID- 1610671 TI - Education: picking up on health. PMID- 1610672 TI - Community care: returning to their historical roots. Interview by Charlotte Alderman. PMID- 1610673 TI - Accidents in elderly care: a randomised controlled trial (part 3). AB - This paper reports the data on accidents from a randomised controlled trial evaluating health authority-funded nursing home and long stay care of the elderly ward care in one inner London health district. Respondents randomised to NHS nursing homes experienced a higher accident rate than respondents randomised to conventional long stay hospital wards for elderly people. Respondents in the homes also experienced an earlier decline in functional and mental ability than those in hospital. These disadvantages have to be balanced against the previously published observational data from the evaluation, which clearly indicated that quality of life in the homes was superior to that in the wards. The conclusion from this study is that earlier decline in functional and mental ability and increased accident risk in the more flexible environments of the nursing homes have to be balanced against an inferior quality of life in the large traditional hospital wards; such assessments are not easy to make on behalf of other people. This final part of the report details the authors' conclusions. PMID- 1610674 TI - Personnel: pre-registration intake changes. PMID- 1610675 TI - Nursing auxiliaries: developing services for elderly people. AB - The establishment of a project to support and develop the role of nursing auxiliaries working with elderly people is described. Organised and run by two clinical facilitators, a variety of research methods, including interviews and non-participant observation of clinical practice, were used to establish baseline data. The interview information showed that there was general dissatisfaction among trained and untrained staff about the auxiliaries' roles, and clinical practice assessment of 206 auxiliaries demonstrated deficiencies in their communication, lifting and infection control techniques. Individual ward development and management of change plans were then set up and operated. PMID- 1610676 TI - Continuing education. Nurses' responses to PREP: a short study. AB - Nurses attending information sessions on the UKCC's Post-registration Education and Practice Project were given questionnaires seeking their opinions on the clauses of the proposals. The results showed enthusiasm for the initiative among those nurses, midwives and health visitors who took part, but reservations about how the recommendations could be put into practice. The implications of the introduction of the measures for a future educational strategy are outlined. PMID- 1610677 TI - Suicide policies in secure environments. AB - A cohort of nurses and prison officers working in regional secure units, special hospitals and prisons were surveyed to establish their attitudes about observation policies designed to prevent patients/inmates from committing suicide. The results suggest that policies are rarely, if ever, reviewed, although there appear to be differences of emphasis in the three environments. Recommendations of the study include the need for improved staff communication, regular review of policies and better preparation of personnel. PMID- 1610678 TI - The medical and nursing approaches to people with mental illnesses. PMID- 1610679 TI - Mary Seacole: the forgotten founder. PMID- 1610680 TI - Chrysalis crisis. PMID- 1610681 TI - Epidermolysis bullosa simplex (Dowling-Meara). A clinicopathological review. AB - The clinicopathological features of 22 cases of the Dowling-Meara form of epidermolysis bullosa simplex (DM-EBS) (11 males, 11 females; aged 5 days-46 years) were reviewed using data collected over a 10-year period. All cases presented clinically within the first 5 days of life. Early blisters were often large (up to 5 cm in diameter), and were mostly acral and particularly periungual. Some cases presented with more widespread erosive skin changes, and two neonates with extensive skin involvement died as a result of overwhelming sepsis. After the neonatal period a different pattern of blistering occurred with more proximal haemorrhagic, herpetiform clusters of blisters. Central healing with recurrent blistering at the margins of these areas was frequently noted. Other physical signs included varying degrees of intra-oral blistering, nail shedding, nail dystrophy, minor scarring, palmo-plantar keratoderma, a lack of seasonal variation and improvement during later childhood. The underlying pathological mechanism in DM-EBS is basal cell cytolysis, or rarely acantholysis, in association with tonofilament (TF) clumping. TF clumping was found in lesional, perilesional and some non-lesional skin, suggesting that the tonofilament abnormality may be of primary aetiological significance in DM-EBS. TF clumping may be due to specific keratin abnormalities because the altered TF were found in a distribution similar to the known distribution of the basal cell keratins, K5 and K14. The level of blistering was invariably very low within the epidermal basal layer and often less than 0.5 microns above the basement membrane. We conclude that DM-EBS is a distinct, and probably under-recognized genodermatosis which tends to have a good prognosis. However, the disease can occasionally be severe, especially during the neonatal period, when it may be confused with junctional or severe recessive dystrophic EB. Electron microscopy is the best means for demonstrating the characteristics cytoskeletal disorder and confirming the diagnosis. PMID- 1610682 TI - Expression of HLA class II antigens on skin fibroblasts in scleroderma. AB - Skin biopsies were taken from 11 patients with morphoea, nine with acrosclerosis and 10 with diffuse systemic sclerosis and processed for immunohistochemical studies using a panel of monoclonal antibodies including antibodies to MHC class II antigens. A significantly higher percentage of HLA-DR positive dermal cells were observed in the reticular dermis in biopsies from patients with morphoea (44.1 +/- 16.2%), acrosclerosis (15.9 +/- 5.4%) and systemic sclerosis (39.5 +/- 2.3%) when compared with the controls (6.6 +/- 2%). A smaller percentage of dermal cells also expressed HLA-DP and -DQ. The degree of monocnuclear cell infiltrate in the biopsies, however, did not correlate with the percentage of HLA class II positive fibroblasts. In organ culture, the expression of the HLA class II antigens was almost totally lost after 3 days and was no longer detected on fibroblasts after 3 weeks of culture. PMID- 1610683 TI - Intravital video-capillaroscopy for the study of the microcirculation in psoriasis. AB - Intravital capillaroscopy using a video-microscopy system permits real-time imaging of the skin microvasculature with retrospective analysis of capillary dynamics. The addition of fluorescein angiography improves contrast and detects aspects of blood vessel behaviour, such as perfusion homogeneity and transcapillary solute diffusion, not detectable under native conditions. This study was performed to evaluate whether the method can be applied to the investigation of a skin disease and in particular the understanding of the role of the blood vessel in the pathogenesis of psoriasis. Results demonstrated clear differences between normal and psoriatic skin. More capillaries were red-cell perfused in both plaque and uninvolved skin compared to normal skin (P less than 0.001) and 0.01 less than P less than 0.02, respectively). The capillaries in psoriatic plaque skin were much larger than those in normal skin (P less than 0.001). The density of capillaries was not increased in plaque or uninvolved psoriatic skin, indicating expansion of existing vessels and not new vessel formation. The area of fluorescence seen around each capillary at 60 s was greater in plaque (P less than 0.001) and in uninvolved psoriatic skin (P less than 0.001) than in normal skin, indicating greater vessel transcapillary diffusion. This study confirms the value of video-microscopy as a non-invasive technique for the examination of the cutaneous microcirculation in vivo. PMID- 1610684 TI - Erythrocyte uroporphyrinogen decarboxylase activity in 80 unrelated patients with porphyria cutanea tarda. AB - To estimate the prevalence of the subgroups of porphyria cutanea tarda (PCT), erythrocyte uroporphyrinogen decarboxylase (UD) activity was measured in 80 unrelated patients with PCT, and in 45 of their relatives by using pentacarboxyl porphyrinogen III as substrate. The subgroups were differentiated by analysis of the urinary porphyrins of the patients and 119 of their relatives. Of the patients, 77.5% were found to be suffering from the sporadic form of PCT (type I PCT), and 22.5% from the familial form (type II PCT). Every patient with PCT had previously been affected by alcohol, oestrogen or some other liver-damaging factor. The relative frequency of familial PCT was higher in females (nine of 15) than in males (nine of 65), which suggests that inheritance of the gene for type II PCT may predispose to oestrogen-precipitated PCT. The onset of type II PCT occurred at a lower age than that of type I (42.6 vs. 47.0 years). The findings suggest an increased risk of precipitating factors in carriers of an inherited UD deficiency. PMID- 1610685 TI - HTLV-1-negative pleomorphic T-cell lymphoma of the skin: the clinicopathological correlations and natural history of 15 patients. AB - The peripheral T-cell lymphomas represent a heterogeneous group and include, besides mycosis fungoides and Sezary syndrome, large-cell anaplastic lymphoma. We report 15 cases from our files that fulfil the histological criteria of pleomorphic T-cell lymphoma with primary skin involvement. Most of the cases were elderly with a male-to-female ratio of 1.5:1. The HTLV-1 serology was negative. The clinical features of these patients differed from those with mycosis fungoides and Sezary syndrome, in that eczematous and precursor lesions such as parapsoriasis en plaque were lacking apart from one exception. All the patients with small-cell pleomorphic T-cell lymphomas were alive, although three of the nine patients with medium-to-large tumour cells have died. Pleomorphic T-cell lymphoma should be regarded as a distinct entity among the lymphoproliferative disorders of the skin. PMID- 1610686 TI - Absence of expression of class II major histocompatibility complex determinants on keratinocytes in bullous pemphigoid. AB - Aberrant expression of class II products of the major histocompatibility complex (HLA-D locus antigens) occurs on keratinocytes in several inflammatory dermatoses and on thyroid epithelial cells in autoimmune thyroiditis. The functional significance of aberrant HLA-D expression is unclear but it has been hypothesized that epithelial cells bearing these determinants may act as antigen-presenting cells for autoantigens. The aim of the present study was to investigate the pathogenesis of bullous pemphigoid using immunohistochemical methods to determine whether the HLA-D locus antigens are aberrantly expressed on keratinocytes in lesional and uninvolved skin. A panel of monoclonal antibodies to each of the HLA D subregions (DR, DP and DQ) and to Langerhans cells was used. Epidermal expression of the HLA-D locus antigens was similar in patients and controls, and there was no significant increase in expression in lesional skin compared with uninvolved skin in six out of nine patients. In three out of nine patients slight enhancement of epidermal HLA-D expression in lesional epidermis corresponded to increased Langerhans cells rather than expression on keratinocytes. HLA-D locus antigens are absent from keratinocytes in bullous pemphigoid skin and aberrant expression of these determinants cannot therefore be implicated in antigen presentation. PMID- 1610687 TI - Modulation of bullous pemphigoid antigen gene expression by gamma-interferon in cultured keratinocytes. AB - Bullous pemphigoid (BP) is characterized by the production of autoantibodies against BP antigens. gamma-interferon (gamma-IFN), a T-cell lymphokine, is known to enhance the expression of several cell-surface proteins. In this study, keratinocytes were cultured in the presence of gamma-IFN, the expression of BP antigen protein was examined by flow cytometry and BP antigen messenger RNA (mRNA) (encoding 230-kDa protein) was quantified by slot-blot hybridization. The results indicated that BP antigen gene expression by keratinocytes was upregulated by gamma-IFN. This enhancement of gene expression was detected at both the protein and mRNA level, suggesting pretranslational regulation. These results imply the involvement of not only humoral immunity but also cell-mediated immunity in the development of BP. PMID- 1610688 TI - A prospective immunofluorescence study of 111 cases of pruritic dermatoses of pregnancy: IgM anti-basement membrane zone antibodies as a novel finding. AB - Since 1981, all pregnant women presenting to our department with a pruritic dermatosis have been investigated by histological and immunopathological techniques. We recruited 111 patients and performed skin histology in 77, 109 direct immunofluorescence tests (DIF), 74 indirect immunofluorescence tests (IIF) and 15 Western blots (WB). We identified: (i) five typical cases of pemphigoid gestationis (PG) (4.5%), corresponding to an incidence of 1/7000 pregnancies. (ii) Five cases without PG but showing circulating anti-BMZ antibodies of IgM type. With the exception of one case, clinical features were homogeneous- occurrence of erythematous papular and/or urticarial lesions on the trunk, and less often, on the limbs between the 32nd and 38th week of pregnancy. Rapid clearance of lesions within a few days was the rule. Whenever performed, DIF was negative and IIF showed circulating anti-BMZ antibodies of IgM type. Western blot studies were negative in these five cases. (iii) One hundred and one cases with negative immunofluorescence tests, considered to be suffering from polymorphic eruption of pregnancy. Our results show the value of systematic immunopathological investigations in pregnant women presenting with a pruritic dermatosis, and raise the possibility of a new entity, as defined by circulating anti-BMZ antibodies of IgM type. PMID- 1610689 TI - Glycosaminoglycan synthesis by cultured human hair follicle dermal papilla cells: comparison with non-follicular dermal fibroblasts. AB - The extracellular matrix of the hair follicle dermal papilla is rich in glycosaminoglycans, the expression of which varies during the hair growth cycle being maximal in anagen and becoming undetectable as the follicle enters telogen. These observations, together with other experimental and clinical evidence, suggest that glycosaminoglycans may be involved in regulating hair growth. To investigate the metabolism of glycosaminoglycans by the dermal papilla we have measured the incorporation of radiolabelled precursors into glycosaminoglycans released into extracellular matrix and culture medium by cultured human dermal papilla cells. We also studied glycosaminoglycan synthesis by cells cultured from the lower follicular connective tissue sheath and by non-follicular dermal fibroblasts. Compared with dermal fibroblasts, dermal papilla cells showed a three to fourfold higher level of incorporation of 35S-sulphate and 3H glucosamine into extracellular matrix glycosaminoglycans. Dermal papilla cells also released more 3H-glucosamine-labelled glycosaminoglycan into culture medium than dermal fibroblasts but there was no difference in 35S-sulphate labelling. These findings indicate that dermal papilla cells maintain a high level of glycosaminoglycan synthesis in vitro. Specific enzyme/chemical degradation showed that dermal papilla cells and dermal fibroblasts synthesized the same glycosaminoglycan types. However, the results suggested that dermal papilla glycosaminoglycans are less sulphated than those synthesized by dermal fibroblasts and that a higher proportion of sulphated glycosaminoglycans is retained in an extracellular matrix. The synthesis of glycosaminoglycans by connective tissue sheath cells was similar to that of dermal papilla cells, supporting the view that the dermal papilla and connective tissue sheath share certain properties. PMID- 1610691 TI - The effect of topical steroids on cutaneous oxygen tension. AB - The precise mode of action of topically applied steroids is unknown. We have applied clobetasol propionate 0.05% ointment (Dermovate; Glaxo Pharmaceuticals) under occlusion to the forearm skin of 10 healthy volunteers for 6 h and monitored transcutaneous oxygen tension at the site for 19 h after its removal. Compared to the ointment base, the steroid-treated area was significantly hypoxic up to 13 h after application. The profound hypoxia present at the site of application of clobetasol propionate 0.05% ointment may account for some of its anti-inflammatory effects, and its atrophogenicity. PMID- 1610690 TI - Treatment of systemic sclerosis with gamma-interferon. AB - Numerous drugs have been recommended for the treatment of systemic sclerosis, but without any significant effect on the fibrotic stage of this disorder. Because recombinant gamma-interferon (gamma-IFN) is a potent and selective inhibitor of fibroblast proliferation and collagen production by human dermal fibroblasts in vitro, we assessed the effects of gamma-IFN treatment on the skin and on pulmonary function in patients with systemic sclerosis. Fourteen patients entered the study, and nine completed the 12-month trial. Fifty micrograms/day of gamma IFN was administered subcutaneously 3 days per week. At the end of the 12-month treatment period a significant improvement was observed in total skin score, and blood gas analysis showed a significant increase in Pa O2 during therapy with gamma-interferon. Other clinical parameters (dysphagia, Raynaud's phenomenon, cardiac involvement) were not altered significantly. No serious adverse effects were noted. These results suggest a beneficial effect of gamma-IFN on the cutaneous fibrotic abnormalities and on lung fibrosis in systemic sclerosis. PMID- 1610692 TI - The effect of zinc and erythromycin on the growth of erythromycin-resistant and erythromycin-sensitive isolates of Propionibacterium acnes: an in-vitro study. AB - The effect of zinc and erythromycin on cultures inoculated with mixtures of different ratios of erythromycin sensitive (ES) and resistant (ER) Propionibacterium acnes cells was studied in vitro. Propionibacterium acnes ES outgrew P. acnes ER in the absence of erythromycin and zinc. At low levels of erythromycin ES outgrew ER, whilst the addition of 600 pg/ml zinc further reduced the growth of ER compared to ES. Growth of ER and ES were similar at levels of erythromycin near the minimum inhibitory concentration (MIC) of ES cells. Concentrations above the MIC for ES cells inhibited ES but not ER cells. At the higher concentrations of erythromycin, the addition of 96 ng/ml zinc delayed the growth of ER cells, whilst the addition of 300 micrograms/ml zinc prevented the growth of ER cells. The combination of erythromycin and zinc, at appropriate concentrations, inhibits both ES and ER. PMID- 1610693 TI - Onychomatrixoma. Filamentous tufted tumour in the matrix of a funnel-shaped nail: a new entity (report of three cases). AB - Identical lesions of the nails were observed in three patients. The main signs were a yellow colouration along the entire length of the nail plate with splinter haemorrhages in its proximal portion, a tendency towards transverse overcurvature of the affected nails, and exposure of a matrix tumour after the nail had been avulsed and the proximal nail fold turned back. The nails signs were striking enough to lead to the clinical suspicion of a filamentous tufted tumour in the matrix of a funnel-shaped nail, an entity not previously described. PMID- 1610694 TI - Cutaneous malignant melanoma and human immunodeficiency virus (HIV) infection: a report of three cases. AB - Cutaneous malignant melanoma was diagnosed in three patients suffering from human immunodeficiency virus (HIV) infection. Staging at presentation inversely correlated with absolute CD4 count. In addition, a notably sparse lymphocytic inflammatory response to the melanoma was observed in two cases. Established data on melanoma in non-HIV immunosuppressed patients suggests a poor prognosis for melanoma in HIV disease. PMID- 1610696 TI - Crohn's disease in association with hidradenitis suppurativa. PMID- 1610695 TI - Spitz naevus of the toe. AB - A 68-year-old Japanese woman presented with a brownish macule, containing two papules, on her left fourth toe. Histological examination revealed an intradermal epithelioid cell tumour with irregularly shaped, bizarre giant cells. In the upper portion of the tumour, the epithelioid cells contained abundant melanin. A low amount of 5-S-cysteinyldopa and a diploid DNA distribution histographic pattern were helpful in differentiating the lesion from malignant melanoma. This location of a Spitz naevus is exceptional. PMID- 1610697 TI - Norwegian scabies and herpes simplex in a patient with chronic lymphatic leukemia and hypogammaglobulinemia. PMID- 1610698 TI - Scarring alopecia and psoriasis. PMID- 1610699 TI - Serum IgE antibodies bind to the epidermal side of the basement membrane zone splits in bullous pemphigoid. PMID- 1610700 TI - Scleredema of Buschke associated with malignant insulinoma. PMID- 1610702 TI - Heterogeneity of the site of origin of malignant melanoma in ungual areas: 'subungual' malignant melanoma may be a misnomer. PMID- 1610701 TI - Molluscum contagiosum; a marker for advanced HIV infection. PMID- 1610703 TI - The clinical spectrum of bacillary angiomatosis. AB - Bacillary angiomatosis is a recently recognized bacterial infectious disease that is seen mainly in patients with the acquired immunodeficiency syndrome. Including this publication, 45 patients have been described in the medical literature. In this report we describe examples of the clinical presentations of bacillary angiomatosis and review therapeutic strategies. PMID- 1610704 TI - Necrobiosis lipoidica: treatment with systemic corticosteroids. AB - In an attempt to find an effective therapy for necrobiosis lipoidica, we have treated six patients with this disease with a 5-week course of systemic corticosteroids. This treatment resulted in complete cessation of disease activity in all patients and no recurrence in a mean follow-up period of 7 months; however, restitution of atrophic skin lesions could not be achieved. The therapy was well tolerated and did not pose problems, even in diabetic patients. These results strongly suggest that short-course therapy of necrobiosis lipoidica with corticosteroids is of lasting benefit to these patients and should probably be considered early in the course of their skin disease. PMID- 1610705 TI - Ultraviolet radiation (UVR) induces cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: a possible mechanism for the UVR induction of cutaneous lupus lesions. AB - Antinuclear antibodies are useful markers of connective tissue disease. In this study, UVB but not UVA induced the expression of Ro/SSA antigen on keratinocyte surfaces in vitro. This expression was also found with the extractable nuclear antigens RnP and Sm, but not with single or double-stranded DNA. The expression was prevented by blocking protein synthesis, suggesting that it was an active process. The results suggest that UVB exposure may result in the expression of Ro/SSA antigen on the surfaces of basal keratinocytes in vivo. This antigen could then bind circulating antibody leading to the cutaneous lesions in neonatal and subacute cutaneous lupus erythematosus. PMID- 1610706 TI - Studies of the microvascular endothelium in uninvolved skin of patients with systemic sclerosis: direct evidence for a generalized microangiopathy. AB - Various parameters for assessing endothelial cell (EC) metabolism, including immunohistochemistry and adenosine uptake, have been compared in the clinically uninvolved skin of patients with diffuse systemic sclerosis (DSS), CREST, incomplete CREST syndrome (ICREST), primary Raynaud's disease (1 degree RD) and normal controls. Evidence of platelet adhesion to EC, decreased EC storage of factor VII-related antigen, changes in EC morphology and decreased adenosine uptake by EC, were found in the dermal microvasculature of normal skin of patients with DSS, CREST and ICREST, but not in 1 degree RD. These data indicate that a generalized microvascular endothelial dysfunction is present in the skin of patients with the systemic forms of scleroderma. PMID- 1610707 TI - Quantification of microvascular changes in the skin in patients with psoriasis. AB - It has been suggested that there is a widespread abnormality of the capillaries in the skin of patients with psoriasis. This study was carried out to obtain more evidence on this point. Lesions of 20 patients with typical psoriasis, and uninvolved skin 3 cm from these lesions, were biopsied and compared with biopsies from 10 normal healthy control subjects. The dermal microvasculature was quantified in all these biopsies with regard to endothelial and luminal volume relative to the volume of dermal components of skin using stereological point counting methods utilizing the Delesse principle. The values for endothelial volume in specimens taken from the centre of the lesions did not differ significantly from those taken from the margins (33.6 x 10(-3) and 35.8 x 10(-3), respectively). The same was true for the luminal volume from the two sites (9.1 x 10(-3) and 10.0 x 10(-3), respectively). There was a highly significant difference, however, between the value for endothelial volume in biopsies from psoriatic patients compared to controls (P less than 0.001) and specimens from uninvolved psoriatic skin also showed a highly significant difference (P less than 0.001) from involved areas. There was no significant difference between uninvolved areas in psoriasis patients and control specimens. Significant differences were also found between values for control subjects and those for both involved and uninvolved psoriatic skin for luminal volume (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610708 TI - Expression of the L-fucose moiety on epidermal keratinocytes in psoriasis induced by the Koebner phenomenon: a sequential study. AB - The expression of Ulex europaeus agglutinin (UEA I) binding sites on cell-surface glycoproteins has been used as a marker for terminal differentiation. Increased number of UEA I binding sites of L-fucose specificity have been demonstrated in psoriatic epidermis. The results of lectin-binding studies in a series of biopsies taken sequentially (0 min, 5 min, 24 h, 7 days and 8 weeks) after tape stripping of uninvolved skin in 12 psoriatic patients (three of whom were taking diltiazem, a calcium blocker at the time of the study) and six controls are presented. UEA I binding sites, which were expressed on the granular layer and upper layers of the stratum spinosum of pre-tape stripped uninvolved skin in psoriatic individuals, were progressively more numerous, with the expression of the L-fucose moiety on the lower stratum spinosum keratinocytes in the 7-day post tape-stripping biopsies and 8-week biopsies, correlating with a moderate and marked increase in the proliferative index, respectively. In the Koebner-negative and non-psoriatic individuals who failed to develop psoriasis after tape stripping, the UEA I binding sites were not expressed on keratinocytes of the lower stratum spinosum in any of the biopsies, although a mild increase in the proliferative index was noted in the 7-day biopsies. Our data suggest that the increased commitment of keratinocytes to terminally differentiate may be involved in the psoriatic process.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610709 TI - The occurrence of pericapillary fibrin in venous hypertension and ischaemic leg ulcers: a histopathological study. AB - The presence of pericapillary fibrin and complement C3c in the ulcers of 19 patients with venous hypertension and 14 patients with ischaemic leg ulcers was investigated using histochemical and immunohistochemical techniques. There was deposition of fibrin around the capillaries in the central part of the ischaemic ulcers, and the venous hypertension ulcers, and in the non-ulcerated skin around one of the venous hypertension ulcers and two of the ischaemic leg ulcers. The deposition of fibrin is a secondary phenomenon that occurs in the area of ulcerated skin and does not play a major causal role in the formation of chronic leg ulcers. PMID- 1610710 TI - Levels of fusidic acid in skin blister fluid and serum after repeated administration of two dosages (250 and 500 mg). AB - The fusidic acid steady-state concentrations in serum (S) and skin suction blister fluid (SBF) after oral doses of 250 and 500 mg administered twice daily for 6 days, as film-coated tablets of sodium fusidate, were studied in eight healthy subjects. The mean peak serum concentrations after the 250- and 500- mg regimens were 39 +/- 5 and 102 +/- 11 mg/l, respectively, obtained between 2 and 3 h after drug intake. The corresponding values for SBF, obtained later, between 2 and 12 h after drug intake, were 21 +/- 5 and 79 +/- 11 mg/l. As measured by the ratio of area under the concentration vs. time curve (SBF/S), fusidic acid penetration is 69-75%, whatever the dose. With either regime, the fusidic acid SBF and serum levels exceed the minimal inhibitory concentration of bacteria usually found in skin infections, especially Staphylococcus species. A dose of 250 mg twice a day appears sufficient to treat these infections and could be tested in clinical studies. PMID- 1610711 TI - The prognosis of patients with lymphomatoid papulosis associated with malignant lymphomas. AB - Lymphomatoid papulosis (LyP) is a disorder which generally runs a benign course, but can sometimes be associated with a malignant lymphoma. Information about the prognosis of these LyP-associated lymphomas is, however, fragmentary. In this study, the clinical data of 50 LyP-associated malignant lymphomas, including 11 patients of our own group and 39 reported in the literature, are evaluated. Three main groups of LyP-associated malignant lymphomas could be distinguished: cases associated with mycosis fungoides (19/50 cases). Hodgkin's disease (12/50 cases) and (CD30+) large-cell lymphomas (16/50). The results of this study demonstrate that patients with mycosis fungoides. Hodgkin's disease, and (CD30+) large-cell lymphomas limited to the skin have a favourable prognosis. However, the prognosis of patients developing a systemic (CD30+) large-cell lymphoma proved generally poor. The results of this study also indicate that the risk of an individual LyP patient developing systemic lymphoma is less than 5%. PMID- 1610712 TI - Re-examining crude coal tar treatment for psoriasis. AB - Two separate, double-blind, randomized, half-and-half body comparisons, each involving 20 in-patients with psoriasis, were conducted to compare the effect of different concentrations of crude coal tar in yellow soft paraffin. The therapeutic effect of 1% crude coal tar used twice daily for 10 days was significantly less than that achieved with an incremental regimen starting at 5% and increasing by 5% every second day to a maximum of 25%. No such difference was seen when a steady concentration of 5% was compared with the same incremental regimen. We conclude that there appears to be no benefit from exceeding a concentration of 5% crude coal tar in yellow soft paraffin in the treatment of patients with psoriasis and that the plateau in the dose-response curve for the action of crude coal tar in psoriasis begins at a point between 1 and 5%. PMID- 1610713 TI - Blisters, ulceration and autonomic neuropathy in carpal tunnel syndrome. AB - We describe three patients with trophic ulceration and blistering of the fingertips associated with carpal tunnel syndrome. One of the patients also had non-insulin-dependent diabetes mellitus. Autonomic neuropathy distal to the carpal tunnel was probably present in all subjects at the time of presentation; in the patient with recent symptoms the skin was warm, and sweating was virtually absent, whilst the other two patients described cold skin, consistent with prolonged autonomic neuropathy. PMID- 1610714 TI - Unilateral bullous pemphigoid in a hemiplegic patient. AB - A 78-year-old man with a long-standing left-sided hemiplegia presented with bullous pemphigoid which affected his paralysed side only. Although the rash was unilateral, direct immunofluorescence demonstrated IgG antibody at the dermo epidermal junction on both sides of the body. Indirect immunofluorescence was also positive. A suction-blister test showed increased skin fragility on the affected side. PMID- 1610715 TI - Consensus conference on cyclosporin A for psoriasis February 1992. AB - Human studies using oral cyclosporin A (CyA; Sandimmun) therapy for psoriasis have been in progress for nearly 9 years. Cumulative data of the clinical effects of this therapy in 1000 patients have been collected, and are derived from multiple open and controlled studies. The efficacy of this treatment in psoriasis is well recognized, and the relative safety of up to 2 years of therapy is also established, provided that the guidelines are observed. However, there is concern regarding the long-term safety of CyA treatment of psoriasis as experience is still limited. Careful monitoring of all CyA-treated patients is therefore mandatory, and CyA should only be used by dermatologists who have expertise in its use. During treatment, co-operation with an experienced nephrologist is strongly recommended. PMID- 1610716 TI - The prefrontal-thalamic axis and classical conditioning. AB - Using the New Zealand albino rabbit as an animal model, it has been determined that the medial prefrontal cortex is intimately involved in, and may be necessary for, acquisition of classically conditioned bradycardia. The interconnected nuclei of the medial thalamus, most notably the mediodorsal nucleus, conversely appear to be associated with the development of the tachycardia that accompanies classical conditioning of the eyeblink and nictitating membrane response. Neuroanatomical, electrophysiological, brain stimulation, and lesion data are reviewed, which support the conclusion that the prefrontal-thalamic axis is intimately involved in acquisition of classically conditioned visceral changes. PMID- 1610717 TI - Cocaine-induced brainstem seizures and behavior. AB - A variety of abnormal sensory/motor behaviors associated with electrical discharges recorded from the bilateral brainstem were induced in adult WKY rats by mechanical (electrode implants) and DC electrical current stimulations and by acute and chronic administration of cocaine. The electrode implant implicated one side or the other of the reticular system of the brainstem but subjects were not incapacitated by the stimulations. Cocaine (40 mg/kg) was injected subcutaneously for an acute experiment and subsequent 20 mg/kg doses twice daily for 3 days in a chronic study. Cocaine generated more abnormal behaviors in the brainstem perturbation group, especially the electrically perturbated subjects. The abnormal behaviors were yawning, retrocollis, hyperactivity, hypersensitivity, "beating drum" behavior, squealing, head bobbing, circling, sniffing, abnormal posturing, and facial twitching. Shifts in the power frequency spectra of the discharge patterns were noted between quiet and pacing behavioral states. Hypersensitivity to various auditory, tactile, and visual stimulation was present and shifts in the brainstem ambient power spectral frequency occurred in response to tactile stimulation. These findings suggest that the brainstem generates and propagates pathological discharges that can be elicited by mechanical and DC electrical perturbation. Cocaine was found to activate the discharge system and thus induce abnormal behaviors that are generated at the discharge site and at distant sites to which the discharge propagates. Cognitive functions may also be involved since dopaminergic and serotonergic cellular elements at the brainstem level are also implicated. PMID- 1610719 TI - Behavioral performance effects of verapamil in normotensive and renovascular hypertensive baboons. AB - Behavioral performances of normotensive and hypertensive adult male baboons were tested before, during, and following chronic oral dosing with verapamil. Performances during a five-color simultaneous match-to-sample task were measured for two doses (2.0, and 3.2 mg/kg/day) and vehicle. Each dose was administered for 21 consecutive days preceded and followed by 14-day baseline and recovery periods, respectively. Choice reaction times increased by 9% during the lower dose of verapamil, compared to vehicle; choice reaction times were unchanged at the higher dose. At baseline and during vehicle administration, the yellow and white stimuli were the most difficult to discriminate correctly; discrimination of these colors was slightly impaired by the lower, but not the higher dose of verapamil. Verapamil's behavioral effects were not modulated by blood pressure changes since both baboon groups showed equivalent changes in behavioral performance, but only renovascular hypertensive baboons showed blood pressure decreases. Verapamil appears to be an effective hypotensive and does not produce profound psychomotor impairment at clinically used doses during the first weeks of treatment. PMID- 1610720 TI - A cry unheard: sudden reductions in blood pressure while talking about feelings of hopelessness and helplessness. AB - This paper describes sudden extreme drops in blood pressure in both experimental and clinical situations when a person is talking about or describing situations of hopelessness and helplessness. These changes are discussed in the context of historical perspectives about the cardiovascular system. A new perspective is introduced, one in which these blood pressure changes are seen as part of an unheard cry for understanding. It is hypothesized that such changes do not occur in response to a person's attempts to communicate a sense of hopelessness, but rather are the biological foundations of the hopelessness itself. Viewed from such a context an entirely new therapeutic approach is outlined regarding the treatment of patients suffering from a wide variety of psychosomatic as well as psychological disturbances. PMID- 1610718 TI - Learning behavior, escape behavior, and depression in an ulcer susceptible rat strain. AB - The aim of the present study was to explore the relationship between depression (helpless withdrawal behavior) and susceptibility to stress ulcer in rats. The WKY genetic strain of rats has been described as highly susceptible to stomach ulcer development during water restraint, i.e., when placed in a jar of water and forced to swim to keep their head above water, a setting in which Richter identified "giving up" behavior akin to hopelessness (Richter, 1957). Since WKY rats tended to float in the water instead of swimming in an attempt to escape, and were also found to be relatively inactive in open field tests, a series of experiments were performed to ascertain whether their diminished activity and their failure to swim reflected slowness, cognitive impairment, or something actually akin to depression. The latter interpretation was supported by evidence from tests of shock avoidance behavior, of capacity to learn discrimination in an operant setting, and by the capacity of an antidepressive drug to lessen floating time in the forced swim test and also to reduce the incidence of stomach ulcers. PMID- 1610722 TI - Looking beyond the numbers. PMID- 1610721 TI - Pavlov's position on the effects of decortication on conditional reflexes. AB - This paper examined D. Joravsky's (1989) hypothesis that I.P. Pavlov dogmatically refused to acknowledge that classical conditioning can be mediated by subcortical regions of the large cerebral hemispheres. Decortication literature from 1901 to 1936 was reviewed. The early studies available to Pavlov, who died in 1936, showed that decortication does not allow the establishment of new or retaining of old conditional reflexes (CRs). G.P. Zelenyi's later experiments(1930) suggested that the establishment of primitive CRs in decorticated dogs was possible. Pavlov never denied this possibility but cautioned that Zelenyi's experiments could have been methodologically flawed. Although Joravsky's original hypothesis on Pavlov's position on the relation between decortication and the establishment of CRs is by and large accepted, it must be stressed that Pavlov's theory of higher nervous activity was primarily concerned with the function of the brain in the higher organism's struggle for existence. Within this context the cortical, rather than subcortical, processes play the decisive role in the organism's adaptation to the changing external environment. PMID- 1610723 TI - Cell kinetics of regenerating liver after 70% hepatectomy in rats--2-color flow cytometric analysis. AB - Two-color flow cytometric (FCM) analysis using anti-bromodeoxyuridine (BrdU) monoclonal antibody (MoAb) was used to investigate the cell kinetics of regenerating liver after 70% partial hepatectomy in rats. Three peaks were seen in DNA histograms of rat hepatocyte nuclei, corresponding to diploid(2c), tetraploid(4c), and octaploid(8c). These proportions changed in the course of regeneration which were clearly demonstrated by DNA histograms using flow cytometry. The proportion of diploid, tetraploid, and octaploid nuclei in control liver were 49.3 +/- 1.6%, 45.0 +/- 7.4%, and 1.7 +/- 0.7%, respectively. A significant change occurred at 24 hours after hepatectomy, as FCM revealed 25.9 +/- 1.1% diploid, 54.5 +/- 1.2% tetraploid, and 9.0 +/- 0.9% octaploid. This shift to polyploid nuclei persisted until 72 hours, and then gradually returned to the pattern of control liver. The S-phase nuclei which incorporated BrdU increased rapidly at 24 hours to a peak of 11.3 +/- 0.9%, and gradually decreased to 5.8 +/- 0.8%, 5.3 +/- 0.8%, 2.4 +/- 0.6%, 2.9 +/- 1.1%, and 1.2 +/- 0.6%, at 48, 72, 96, 120, and 168 hours, respectively. This 2-color FCM analysis made a detailed analysis of the cell kinetics in regenerating hepatocytes possible, and may be applied in investigations of various aspects of liver regeneration. PMID- 1610724 TI - Pancreaticojejunostomy for severe symptomatic chronic pancreatitis. AB - The role of operation, particularly pancreaticojejunostomy, in the treatment of abdominal pain from chronic pancreatitis is controversial, but relief of pancreatic duct obstruction may decrease the rate of pancreatic organ failure. Our results over 6 years in 13 carefully selected patients suggest that pancreatic drainage does relieve pain but is less effective in preventing pancreatic exocrine failure. Pain was the indication for operation in all patients. PMID- 1610726 TI - Duodeno-jejunal varicosities following extrahepatic portal vein thrombosis. AB - A 31 year old man, under investigation for melena, was found at endoscopy to have varicosities at the site of a duodeno-jejunostomy which had been performed for duodenal atresia when he was three days old. Angiography revealed an occluded portal vein with an extensive collateral circulation. At laparotomy some of the collateral vessels were found to pass through the anastomotic site and directly into the left lobe of the liver. The portal pressure was found to be minimally elevated. Resection of the anastomotic segment was performed with reconstruction using a Roux en Y jejunal loop. Bleeding from collateral vessels passing through an anastomosis site in a patient with extrahepatic portal vein thrombosis has not previously been reported. PMID- 1610725 TI - Prospective evaluation of ultrasonic surgical dissectors in hepatic resection: a cooperative multicenter study. AB - Blood loss is the major cause of postoperative mortality and morbidity associated with hepatic resection. A prospective multicenter study was conducted to determine if ultrasonic dissectors (USD) were useful in hepatic resection and could reduce this hemorrhagic risk. Forty-seven hepatic resections were performed in 42 consecutive patients during a two month period in 11 public, surgical centers. Twenty-one patients had primary or secondary malignancies, six had benign tumors, two had biliary cysts, one had cholangiocarcinoma, one had Caroli's disease, and 11 had hydatid cysts of the liver. Two different USD devices were evaluated (CUSA System-Lasersonics and NIIC-DX 101 T). The hepatic resections tested included a wide range of procedures. Each surgeon had the possibility of choosing between the USD and his own usual technique for each operative step and according to local conditions. The average volume of blood infused, irrespective of the underlying pathology or the procedure performed, was 1.0 L (range 0-4.8 L). Fourteen patients required no transfusions. No operative or immediate postoperative deaths were recorded. Five major complications, all unrelated to the use of the USD, developed in three patients. Access to intra and extraparenchymal arterial and venous tributaries and particularly the control of the hepatic veins were facilitated by USD. While transection of hepatic parenchyma was neither easier nor faster than with conventional techniques, it was found to be less hemorrhagic. Overall appraisal was expressed on an analog scale; the USD was found to be helpful or very helpful in 75 percent of all resections. With regard to the pathology being treated, total or partial excision of hydatid cysts was greatly enhanced by the use of the USD while this benefit was not found for wedge resections of other hepatic lesions. With regard to user friendliness and maintenance, the NIIC-DX 101 T device was preferred. We conclude that the USD facilitates formal hepatic resections. Converging opinions emerging from various surgical centers reinforce this conclusion. PMID- 1610727 TI - Postoperative appearances of the liver on ultrasonography following hydatid cyst surgery. PMID- 1610728 TI - Long-term results of choledochoduodenostomy. PMID- 1610729 TI - A review of pancreatico-pleural fistula in pancreatitis and its management. AB - Pancreatico-pleural fistula is a rare condition in which pancreatic enzymes drain directly in to the pleural cavity, most commonly from an enlarging pseudocyst. We review the literature on the causes, investigations and treatment of pancreatico pleural fistulae and compare this with our own experience of the case of a 41 year old man with a left sided pancreatico-pleural fistula associated with pancreatic duct obstruction. The fistula could not be demonstrated by USS, CT or ERCP, and after these investigations the patient was managed conservatively. However, deterioration in the patients' condition led to an urgent but not emergency laparotomy and operative pancreatogram. This demonstrated the distally obstructed pancreatic duct, with associated pleural fistula for which aggressive surgical intervention was indicated. The patient subsequently completely recovered. PMID- 1610730 TI - Arterioportal fistulas (APF) in liver tumors: prognosis in relation to treatment. AB - Prognosis of 16 patients with hepatic tumors and angiographically proven arterioportal fistulas was analysed in relation to treatment. Six patients received only conservative therapy; they all died of variceal bleeding in the course of two months after angiography. Hepatic resection was performed in four patients; three of them are still alive 13-52 months later including two free of both the tumor and portal hypertension. Hepatic artery embolization was carried out in six patients. All of them died in 2-36 months after the procedure, but only two from gastroesophageal hemorrhage. It is concluded that prognosis of arterioportal fistulae in liver neoplasms is poor due to hyperkinetic portal hypertension and following variceal bleeding. Hepatic resection of both the tumor and the fistula is the treatment of choice. In unresectable cases hepatic artery embolization will decrease the risk of variceal hemorrhage. PMID- 1610731 TI - The immobilization of glucose oxidase onto radio-frequency plasma-modified poly(etherurethaneurea). AB - Glucose oxidase was covalently immobilized onto a radio-frequency plasma-modified poly(etherurethaneurea). Thin (90-100 nm) plasma-polymerized N-vinyl-2 pyrrolidone films were deposited onto poly(etherurethaneurea) films. Active sites for the immobilization were obtained via reduction with aqueous sodium borohydride and activation with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate. Modified poly(etherurethaneurea) films were assayed for binding and activity of the immobilized glucose oxidase layer. The results of a modified radioimmunoassay and an 'immunochemical stain' indicated that washing in 900 ml of continuously stirred 2% sodium dodecyl sulfate, 2% Triton X-100, and 20 mM sodium phosphate, pH 7.0, for 24 h each at 4 degrees C was necessary to remove physically adsorbed glucose oxidase from the solid supports. An amperometric activity determination in 9 ml of well-stirred 20 mM sodium phosphate-0.1 M sodium chloride, pH 7.4, gave a qualitative demonstration of the activity of the immobilized enzyme on 18.75 cm2 of modified poly(etherurethaneurea) film. A colorometric activity determination using the coupled reaction with o-dianisidine and peroxidase indicated that glucose oxidase covalently immobilized on approximately 2.4 cm2 of modified poly(etherurethaneurea) film had an activity approximately equal to that of 13.4 nM glucose oxidase in 50 mM sodium acetate, pH 5.1, with a specific activity of approximately 32.0 U/mg at pH 5.1 and room temperature. PMID- 1610733 TI - Surface characteristics and blood compatibility of polyurethanes grafted by perfluoroalkyl chains. AB - Polyurethane (PU) surface was chemically modified by grafting of perfluorodecanoic acid (PFDA) to produce a highly hydrophobic surface to compare the blood compatability with hydrophilic poly(ethylene oxide) (PEO) grafted PUs. The advancing contact angle of modified PU-PFDA was increased up to 115 deg, while that of untreated PU was 86 deg. The PFDA grafted PU exhibited less adhesion and shape change of platelets than untreated PU, and the activated partial thromboplastin time (APTT) of PU-PFDA was considerably extended. The ex vivo occlusion time of untreated PU was only 50 min, but that of PFDA grafted PU was extended to 130 min, indicating that this hydrophobic surface is significantly blood compatible. It is interesting to find that the enhanced blood compatibility of very hydrophobic PU-PFDA was equivalent to hydrophilic PU-PEO. PMID- 1610732 TI - Synthesis of a novel polyurethane co-polymer containing covalently attached RGD peptide. AB - The synthesis of a novel polyurethane block co-polymer containing a covalently attached, well-oriented RGD (Arg-Gly-Asp) peptide was explored. A poly(tetramethylene oxide) (PTMO)-based polyurethane was synthesized, and a bimolecular nucleophilic substitution reaction was then employed to incorporate ethyl carboxylate groups onto the polymer backbone (i.e. carboxylated polyurethane). Elemental analysis was used to determine the extent of carboxylation. The hexapeptide H-Gly-Arg-Gly-Asp-Ser-Tyr-OH was coupled to the carboxylated polyurethane via the formation of an amide bond. The attachment of the peptide was controlled by a protection-deprotection scheme. Nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies were used to monitor the reactions. Sakaguchi assay and amino acid analysis confirmed that the RGD-containing peptide was successfully grafted onto the carboxylated polyurethane. This reaction scheme provides a new route for grafting end-linked, bioactive peptides onto polyurethanes. PMID- 1610734 TI - Surface-modulated skin layers of thermal responsive hydrogels as on-off switches: II. Drug permeation. AB - 'On-off' regulation of drug permeation through membranes in response to external temperature change has already been achieved using thermosensitive copolymers of N-isopropyl acrylamide (IPAAm) with butyl methacrylate (BMA). Increasing temperature induced formation of a dehydrated polymeric surface skin layer that stopped drug permeation. In this study, to control 'on-off' permeability of a drug, the polymer surface shrinking process was regulated by changing the length of alkyl side chain of the copolymer methacrylate component. Permeation experiments with indomethacin were performed in response to stepwise temperature changes between 20 and 30 degrees C with copolymers of IPAAm with BMA, hexyl methacrylate (HMA), and lauryl methacrylate (LMA). Burst permeation was found at the initial stage of the second 'on' period for both poly(IPAAm-co-HMA) and poly(IPAAm-co-LMA). These results suggest that drug diffuses during 'off' periods to change the concentration profile in the polymer gel. Polymer surface skin formation maintains a localized high water content inside the polymer gel even if drug permeation stops. The length of the alkyl side chain is an important parameter to control 'on-off' permeability of drug. PMID- 1610735 TI - Adhesion and proliferation of bovine aortic endothelial cells on monoamine- and diamine-containing polystyrene derivatives. AB - Adhesion and proliferation of bovine aortic endothelial cells on polystyrene derivatives having monoamine or diamine side chain was investigated focusing on the chemical structure of amino groups. Copolymers, SE8.5, is composed of polystyrene with 8.5 mol% of monoamine side chains, and SED8, which is with 8 mol% of diamine side chains, were estimated to contain almost the same amount of protonated amino groups in bulk composition at physiological pH (pH 7.4). There observed significant difference in cellular spreading of attached endothelial cells between these two types of copolymer surfaces. Spreading-% of attached cells on SED8 surfaces was approximately 1.6 times greater than that on SE8.5 6 h after seeding. This difference in cellular spreading influenced to subsequent cell growth. Cellular growth on each polymer surface was featured by parameter k, which corresponds to the 'rate constant' of cellular proliferation. While the k value for SE8.5 decreased with decreasing seeding density as well as the case for polystyrene, SED8 maintained a high k-value even at low seeding density as 2 x 10(3) cells/cm2. These results suggest that cells may recognize the difference in the chemical structure of amine side chains of SE and SED copolymers. PMID- 1610736 TI - Low temperature incorporation of bovine serum albumin into a bead formed macroporous hydrophilic polymer matrix with potential for sustained release. AB - A process of freeze-thaw polymerization involving the low temperature photopolymerization of a mixed solution of monomers and bovine serum albumin around frozen ice crystals has been used to generate a bead formed macroporous hydrophilic matrix with potential for sustained release. Beads over the size range 100-3000 microns were fabricated with surface and internal pores of between 0.7-2.6 microns whose diameter could be controlled by manipulation of the monomers to solvent ratio. Increasing both the proportion of monomers in the monomer solution and the percentage of BSA incorporated reduced the EWC of beads. The BSA release profile was characterized by an initial burst followed by a lower but sustained release lasting up to 1 month. The total cumulative release of BSA and the proportion of the incorporated BSA load subsequently released were both reduced in physiological saline compared with distilled water but enhanced by freeze drying, mild agitation and incubation at 37 degrees C. PMID- 1610737 TI - Gastric compliance and motility in the portal hypertensive rat. AB - In an ex vivo rat model, we compared the intraluminal pressure response of both the whole stomach and the antrum to progressive intraluminal distension in portal hypertensive and sham-operated rats. In both groups, this response featured a biphasic change in tone with superimposed phasic pressure waves. While the tonic pressure response to distension (reflecting gastric compliance) was similar in both groups, the frequency and amplitude of antral phasic pressure waves (reflecting antral motility) were greater in the portal hypertensive animals. These studies indicate that portal hypertension does not alter gastric compliance but is associated with an exaggerated antral motor response to distension, suggesting that this latter mechanism, rather than impaired accommodation, may explain the accelerated gastric emptying described previously in the portal hypertensive rat. PMID- 1610738 TI - Use of myxalin for improving vascular graft healing: evaluation of biocompatibility in rats. AB - Myxalin is a glycopeptide extracted recently from a gram-negative bacterium. It has blood anticoagulant properties and can enhance endothelial cell growth. With the ultimate objective of using this bioactive molecule to promote vascular graft healing, this study assessed its biocompatibility in vivo by comparing the cellular and immunological responses of gelatin-coated knitted polyester grafts with and without myxalin following implantation in the peritoneal cavity of rats for prescheduled periods of 3 days and 1, 2, and 4 weeks. A nongelatin-coated virgin polyester graft was included as the reference material. The biological response to gelatin alone was characterized by a slower rate of cellular infiltration into the implant, reduced collagen synthesis, and higher levels of acid phosphatase and esterase activity in the surrounding tissue. The addition of myxalin to this coating resulted in a significant reduction of hydrolase secretion in the tissue surrounding the implant and an enhancement of cellular ingrowth. PMID- 1610739 TI - Multiple in vivo full-thickness myocardial biopsies by freeze-clamping. AB - A technique was developed to permit multiple large biopsies of the in vivo myocardium to measure certain metabolites (ATP, CP, myocardial glycogen, lactate) with minimal chance of ventricular fibrillation or severe alterations in the heart's ability to maintain BP. Adult pigs with normal hearts (n = 9) as well as with hypertrophy (n = 5) created by aortic banding 3-4 months prior were anesthetized, intubated, and ventilated. After a sternotomy, the pericardium was opened and the epicardial surface was cleared of any adhesions. Biopsies were taken from the distal to proximal end of the heart. A suture (3-O Prolene) was placed in a figure-eight pattern in the area to be biopsied. A piece of the myocardium (50-100 mg) was grasped using a pair of narrow dressing forceps and frozen in liquid nitrogen. When the sample was completely frozen, a No. 11 scalpel blade, held at a 90 degrees angle to the epicardium throughout the cut, was used to carve out the full thickness biopsy. The sample was placed immediately in liquid nitrogen. The myocardial defect was repaired by using the previously placed suture buttressed with pieces of subcutaneous fat to prevent tearing the epicardial surface. This in vivo biopsy method has negligible complications and can be repeated or taught with constant reliability. PMID- 1610740 TI - Effect of calcium alginate dressings on partial-thickness wounds in swine. AB - The epithelization of partial-thickness wounds (PTW) has been shown to be enhanced with the use of moisture-retentive dressings (MRD), and not with nonmoisture-retentive dressings (NMRD) like gauze. This study was designed to explore this effect using two different alginate products with and without MRDs. We evaluated these alginate dressings under a polyurethane film dressing (FMRD) and under an NMRD gauze. They were compared to hydrocolloid moisture-retentive dressings (HMRD). Twelve PTW measuring 22 x 22 x 0.5 mm were made on the dorsum of six swine with a Castroviejo dermatome. Return of the epithelial barrier function was measured with an EP1 ServoMed evaporimeter. On postoperative day 4, the first alginate product under the NMRD and under the FMRD had a significantly slower healing rate than the HMRDs. By postoperative day 7, the second alginate product under the NMRD had a poorer rate of epidermal wound healing than the HMRD. Our results indicate that these alginate products have a satisfactory partial-thickness wound healing capability when used under MRDs. When used under MRDs, the return of the epithelial barrier function is delayed, indicating that these dressings should not be used on dry wounds or under gauze dressings. PMID- 1610741 TI - Successful cryopreservation of microvenous allografts. AB - Vein grafts are used in approximately 20% of microsurgical cases. Although autogenous veins currently form the major source, they are associated with increased operating time and donor site scars. Cryopreserved allograft veins may serve as an alternative source. To our knowledge, cryopreservation of veins (1 mm or less) has not been reported. In this article we have described the process of cryopreserving rat veins (less than 1 mm in diameter) and their preliminary use as interpositional vein grafts. PMID- 1610742 TI - Difficulties in duplicating the human upright, graviportal, plantigrade posture in sitting, standing, and walking by the use of animal models. PMID- 1610743 TI - Markowitz Award recipient: Charles O. Bechtol 3d, MD. PMID- 1610744 TI - Review of the carotid artery loop procedure in sheep. AB - Carotid loop (CL) surgery involves the permanent externalization of a common carotid artery in a skin tube. The CL facilitates repeated access to the systemic arterial system for blood sampling and blood pressure measurement in laboratory sheep. It eliminates the need for arterial cut-downs and chronic indwelling catheters, reduces the risk of sepsis and infection, and adds flexibility to research protocols. The surgical procedure is aseptically performed under general anesthesia and involves isolation of the common carotid artery, creation of a bipedicled skin tube, and permanent envelopment of the artery in the skin tube. The primary complication is ischemic necrosis with sloughing of the middle of the loop and is usually due to failure to adhere to the critical length-to-width ratio (2.5:1). We have performed 150 CL procedures with an overall success rate of 94%. Nine CL ablations were required, due to necrosis with exposure of the artery (7/9) or stricture formation with loss of patency (2/9). Twenty-two CLs developed complications secondary to partial necrosis, but did not require ablation. Results indicate that the CL is a reliable method to ensure repeated access to the systemic arterial system in sheep. A modification of the standard CL procedure in which the artery is surrounded by a skin tunnel rather than enclosed in a skin loop was performed in 10 sheep. Preliminary results indicate significant reduction in the incidence of complications associated with the standard CL. PMID- 1610745 TI - In vivo strain analysis of the greyhound femoral diaphysis. AB - Subminiature single element and rosette strain gauges used for deformation measurement were prepared for surgical implantation using a technique published previously (Szivek JA, Magee FP. J Invest Surg. 1989;2:195-206). During surgery, gauges were placed on the anterior, lateral, and medial aspects of the mid diaphysis of one femur in six greyhounds. Motion and gait analyses were performed to ensure uniform weight bearing prior to strain monitoring. In vivo strain measurements were obtained during normal gait at several speeds on a treadmill. After a 3-month holding period, strain gauges that were implanted on the contralateral femur were monitored. All animals were euthanized and both their femora explanted. Following embedding and histological preparation of the explanted femora, strain measurements were plotted on diagrams of the section shapes of the mid-diaphysis of each femur. Strain distribution diagrams indicated that peak strain levels and strain distributions changed during different phases of gait. Increases in gait speed increased the peak strain levels. In addition, the anterior rather than anterior-lateral aspect of the femur exhibited the highest strain during midstance. Measurements taken from rosette gauges indicated that the principal compressive strain direction was oriented slightly off axis to the long axis of the femur. Measurements from gauges placed along the length of the femur indicated an average strain change of 22.3 microstrain +/- 12.2% over a 2-cm length in the mid-diaphysis. These measurements provide a baseline describing the strain state of the greyhound femur and can be used in computer modeling. PMID- 1610746 TI - Arthroscopy of the knee in children and adolescents. AB - Arthroscopy of the knee was performed in 104 patients under 18 years of age, 41 in children (aged 8 to 15) and 63 in adolescents (aged 16 to 18). Most frequently lesions of the patella were found (in 45% of all diagnoses in children and 29% in adolescents), in most cases because of acute or recurrent dislocation of the patella. The incidence of meniscal lesions increased with age. The most frequent therapeutic procedure performed in children was a lateral release (34%), in adolescents a partial meniscal resection (31%). In children 43% of arthroscopies were diagnostic, in adolescents 21%. Preoperative diagnosis was shown to be incorrect or incomplete arthroscopy in 41% of children and 24% of adolescents taking arthroscopic findings as a golden standard. Preoperative diagnosis had highest accuracy for dislocation of the patella, 90% of dislocations were diagnosed correctly before arthroscopy. The lowest accuracy of clinical diagnosis was found for meniscal lesions; only 36% of meniscal tears were suspected preoperatively. In 35 of 38 patients with hemarthrosis a relevant knee lesion was found, in 23 of these patients arthroscopic therapy was performed. This justifies our concept for arthroscopy of every knee hemarthrosis. Besides superficial chondral lesions in 8 patients there were no complications associated with the procedure. It is concluded that arthroscopy of the knee in children and adolescents is a safe procedure with high diagnostic and therapeutic value. PMID- 1610747 TI - Ectopic thymic tissue simulating--a posterior mediastinal mass. AB - A 4-month-old male child underwent a thoracotomy for a suspected posterior mediastinal mass. Ectopic thymic tissue was found. Ectopic thymic tissue should be included in the differential diagnosis of a posterior mediastinal mass in a child. PMID- 1610748 TI - Central hamartoma of the liver in a child. AB - A two-year-old girl was found to have a hamartoma of the liver located centrally in the hilar region. Despite the benign character of this lesion severe biliary obstruction developed rapidly and made surgical therapy necessary. The surgical approach, with reference to the literature, is discussed. PMID- 1610749 TI - Postoperative management of children with biliary atresia and heart failure. AB - The postoperative course in two children with extrahepatic biliary atresia and cardiovascular disease was reviewed and the correlation between biliary drainage and cardiac function was analyzed. Both patients obtained satisfactory biliary drainage after Kasai's hepatic portoenterostomy. One patient developed heart failure postoperatively due to severe viral myocarditis. This child's total serum bilirubin concentration remained elevated for eight months, despite adequate bilirubin excretion, until her cardiac function returned to normal. Another patient died of cardiac failure due to congenital heart disease 83 days after Kasai's operation, but his postoperative biliary drainage was satisfactory as long as cardiac function remained compensated. In both cases, fluid intake was restricted severely (30 to 70 ml/kg body weight/day), as titrated by echocardiographic assessment of cardiac function, but biliary excretion was satisfactory as long as the cardiac fractional shortening ratio was greater than 30% and the ejection fraction was greater than 55%. This suggests that cardiac decompensation affects postoperative biliary excretion in patients with biliary atresia; however, with careful medical management satisfactory biliary drainage can be achieved even in patients with severe heart diseases. PMID- 1610750 TI - Histological investigation of the myenteric plexus of the entire gut in an infant with hypogenesis of the intestine. AB - A male infant with pseudo-Hirschsprung's disease was treated for 2 years and 10 months, then died of severe enterocolitis. At autopsy examination of the entire gut was possible, and a definite histological examination could be performed which threw light on the pathogenesis. The ganglion cells of the esophagus, stomach, small intestine, colon and rectum were examined, diameters of their nuclei were measured, and their nuclear volumes were calculated. S-100 and anti neurofilament stainings were also performed in an immunohistological investigation of the glial cells and nerve fibers. Both the diameter of the volume of the nuclei of the ganglion cells in the small intestine and colon were significantly smaller than normal. Even in the esophagus the nuclear volume was smaller than normal. The glial cells and nerve fibers gradually decreased in the caudal direction. Thus, histomorphometry and immunohistochemistry both showed that the neuroblasts in the intestine were immature and the migration of ganglion cells was disturbed in this case. The final diagnosis was hypogenesis of the intestine. PMID- 1610751 TI - BCG osteomyelitis as a rare cause of mediastinal tumor in a one-year-old child. AB - A one-year-old child with BCG osteomyelitis of the upper spine is reported. The child was admitted because of viral infections of the upper respiratory tract. A lateral x-ray examination of the lung showed what was thought to be a mediastinal tumor. The preoperative diagnostic problems are discussed, because the etiology in our case was unknown until the histological report arrived. The knowledge of the complication, of osteomyelitis after vaccination, is small although the first case was published more than 40 years ago. Since then about 300 cases have been reported in the literature. The disease is seen in the first five years of life in otherwise healthy children. Most cases are localized near the epiphysis of the long bones. A localization in the spine, as described in our case, has been published only three times before. The highest frequency of BCG osteomyelitis is reported in Finland and Sweden with about 40 cases per 1 million vaccinations. PMID- 1610752 TI - Osteomyelitis of the femoral neck caused by a pencil stab wound. AB - A unique case of osteomyelitis of the femoral neck of an eleven-year-old boy, following a stab wound by a lead pencil, with reactive synovitis of the hip joint is presented. The clinical course simulated that of acute septic arthritis and was diagnosed by various imaging modalities. Following operation and systemic antibiotic treatment, the patient improved dramatically. The role of sonography in the presence of inflammatory conditions around the hip joint is emphasized. PMID- 1610753 TI - Urinary diversion in children. AB - At the present time, urinary diversion in children remains an last resort type of treatment that must be carried out in selected cases when there is no alternative available. All forms of urinary diversion have the common goal of gaining control of a life-threatening situation; all, however, are fraught with serious disadvantages for the affected children. The newer forms (undiversion, pouch, ileocystoplasty, augmentation) undoubtedly improve the patient's quality of life, but the risks of long-term metabolic and renal complications and malignant degeneration persist. Harzmann, who for years has concerned himself with urinary diversion and, in particular, with malignant changes, has posed two difficult questions: 1. Is urinary diversion using bowel segments defensible for benign disorders, e.g., in children? 2. Which follow-up examinations should be performed after urinary diversion using bowel segments, and at what time intervals? Our goal should be to keep the number of urinary diversions as small as possible by means of appropriate treatment, prophylaxis, and in particular the means and type of primary reconstructive therapy. Children have a life-time ahead of them, and the complications of urinary diversion increase decade by decade. This fact has been demonstrated in children who have undergone ureterosigmoidostomy or ileal conduit. Grounds for the assumption that fewer serious long-term complications are to be expected after colon conduit, pouch, neobladder, or augmentation procedures have not been established. PMID- 1610754 TI - Feeding troubles following delayed primary repair of esophageal atresia. AB - Severe feeding troubles were recorded in five babies with long-gap esophageal atresia who underwent, between 1985 and 1990, a delayed primary anastomosis after spontaneous growth of their esophageal stumps. A comparison with 20 cases of direct esophageal anastomosis, operated on in the same period, was carried out by means of recorded esophagrams, pH monitoring and questionnaires charting the growth pattern and feeding habits of the patients. Bottle feeding, and, later on, the introduction of semi-solid foods was significantly retarded in the group of children with delayed primary anastomosis (labeled as group B) as well as height and weight parameters. Failure to complete feeds, dysphagia, vomiting, coughing, choking and recurrent respiratory symptoms were also significantly more common in this group than in the primary anastomosis group (labeled as group A) even in the absence of stricture. Variable degrees of disordered esophageal motility were present in all patients but pooling of the contrast medium, retrograde flow and delayed clearing of the esophagus were more frequent in group B. No patient was shown to have associated hiatal hernia. A 24 hour pH recording showed severe gastroesophageal reflux in 4 out of 13 cases of group A and in 3 out of 5 cases of group B. Clearing times were significantly delayed in all refluxing children. Our data suggest that the retarded start of oral feeding and swallowing coordination in patients with delayed primary anastomosis add further negative factors to their congenitally impaired esophageal motility, causing protracted dysphagia which represents a major problem for both family and hospital staff. PMID- 1610755 TI - Reconstruction of the arteria carotis communis in newborn following extracorporeal membrane oxygenation (ECMO). AB - With the help of ECMO it is possible to save the lives of newborn infants suffering from severe respiratory distress syndrome not responding to conservative treatment. Using Bartlett's classic venous-arterial perfusion technique in ECMO the right arteria carotis communis had to be sacrificed. Thus, despite the life-saving character of this new method, the ligation of the carotid with all its possible complications had often been a major argument against using this therapy. We are now therefore trying to reconstruct the arteria carotis after decannulating the vessel after extracorporeal membrane oxygenation. In our 8 cases so far, post-op examinations showed no obstruction of blood flow in the vessel. No neurological deficiencies were recorded. PMID- 1610756 TI - Indication for using extracorporeal membrane oxygenation in congenital diaphragmatic hernias and pulmonary hypoplasia. AB - Despite the apparent surgical simplicity of the anatomic defect, congenital diaphragmatic hernia continues to be a critical problem in neonatal surgery, so that survival is still uncertain. Therefore, we must realize that the barriers to survival are pulmonary parenchymal and vascular hypoplasia as well as the complex syndrome of persisting fetal circulation. However, new treatment methods, such as extracorporeal membrane oxygenation (ECMO), although controversial, may improve survival. We believe that no infant should be excluded from diaphragmatic repair or consideration for ECMO-support before accurate predictive parameters have been developed that take both pulmonary hypoplasia and pulmonary hypertension into account. ECMO additionally enables us to postpone the operation until stabilization of the newborn (Late Operation Protocol). Apart from this, we can probably improve the long-term results after ECMO by reconstructing the common carotid artery. PMID- 1610757 TI - Surgical treatment of hepatic hydatid disease in children. AB - Fifty-one patients were operated on because of hydatid disease of the liver from 1980-1990. There were 29 male and 22 female patients with a mean age of 10 years (range 3 to 15 years). Thirty-two cysts were located in the right lobe, 6 were in the left lobe and 13 were bilateral. Introflexion was carried out in 27 patients, omentoplasty in 12, marsupialization in 8, capitonnage in 3 and total cystectomy in one patient. There were no deaths. Postoperative morbidity and mean postoperative stay were the lowest in patients treated by introflexion. We concluded that introflexion is a safe and valid surgical technique for patients with hydatid liver disease. PMID- 1610758 TI - The changing role of surgery in the management of rhabdomyosarcoma. AB - A retrospective analysis was performed of 56 patients presenting to Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland, over a 25 year period with a diagnosis of rhabdomyosarcoma, in an effort to assess the changing role of surgery in the management of this disease. There were 38 males and 18 females; the age range at presentation was from birth to 13 years with a median of three years. Head and neck tumors occurred most frequently (23) followed by pelvic (14), paratesticular (6), extremities (6), gastrointestinal (4) and thoracic (3). Prior to 1971 there were no survivors while a doubling of survival has been observed within the past decade (31% to 63%). The minimum period of follow-up was four years. Surgical intervention ranged from total primary excision (20) to biopsy only (21) with total or subtotal resection performed electively in 15. Surgical evaluations, including examinations under anesthesia, staging laparotomy and second look laparotomy were also invaluable in assessing disease status. The incorporation of multiagent chemotherapy together with more selective use of radiotherapy has enabled a more conservative role to be adopted by the surgical oncologist thereby minimizing longterm sequelae. PMID- 1610759 TI - The effects of elemental diet following ileo-endorectal pull-through in rats. AB - Total colectomy, mucosal proctectomy and ileo-endorectal pull-through (IEP) have been carried out mostly in dogs, because of high mortality after IEP in rats. This report evaluates the effects of elemental diet on bodily metabolism and survival following IEP in the rat. Survival at 4 weeks was 100% in the sham operated group used as controls, 80% in IEP group given laboratory food + 10% Vivonex ten (group 2), 30% in IEP group given food + 1/2 saline (group 3), and only 10% in IEP group given food + water (group 1). The serum Na, Cl, HCO3 were significantly lower from day 3-7 to day 28 in the group 1. On the contrary, both serum K and osmolality were extremely elevated in the group 1. The total protein level also increased gradually in the group 1 due to extracellular fluid loss. Groups 2 and 3 maintained bodily metabolism related to water and electrolytes well. Our data support the suggestion that severe water and electrolytes imbalance may occur following total colectomy. A supplementary elemental diet prevents water and electrolyte depletion and improves survival following total colectomy and IEP in the rat. PMID- 1610760 TI - Outpatient catheterless Mathieu repair: how to cover ventral penile skin defect. AB - A modification of the Mathieu repair eliminating stenting has been described by Rabinowitz which makes the method more convenient for outpatient performance. We report on our experience with this modification with special emphasis on coverage of ventral penile skin defect. To cover the raw area formed on the ventral aspect of penis with the creation of meatal based flap Rabinowitz used Byar's flap. Two different flaps prepared from prepuce were used in this series. In some patients an island flap was used. In others the prepuce was incised transversally on its dorsal aspect and transferred to the ventral surface as a bipedicle visor flap, as described by Ombredanne and popularized by Nesbit. Twenty-two patients ranging in age from one to twelve years (mean +/- 1SD = 6 +/- 3.28) were operated on using the technique. The meatus was glandular in two, coronal in twelve and distal penile in eight patients. Preputial flap was not used in one patient because the defect was small. Island flap was used in three and Ombredanne Nesbit's flap in 18 patients. Complete disruption of the repair occurred in one of the patients in whom an island flap was used. Among 18 patients in whom Ombredanne-Nesbit's flap was used, one partial necrosis of the preputial flap was encountered which required revision and two urethrocutaneus fistulae occurred which healed spontaneously. The use of the present technique yields a good cosmetic result, a high success rate with minimal complications, and eliminates catheterization; hence, hospitalization is recommended. PMID- 1610761 TI - Argyrophilic staining for nucleolar organizer region (AgNOR). A suitable methodology for differential diagnosis of breast lesions? AB - Argyrophilic (Ag) staining for nucleolar organizer regions (NORs) is now emerging as a useful means for confirmation and exclusion of malignancy, discriminating features being the number, morphology and distribution of AgNORs. We have put the validity of this method to the test by comparing a series of potentially problematic breast lesions: atypical epitheliosis (n = 22) versus carcinoma in situ (n = 16) and sclerosing adenosis (n = 11) versus invasive carcinoma (n = 20). Malignant epithelial cells contained, in general, more AgNORs than benign proliferation but there was overlapping and the method could reliably differentiate only between sclerosing adenosis and invasive carcinomas (P less than 10(-6). In the latter, irregularity and intranuclear dispersal of AgNORs were prominent features. The conclusion is drawn that increased AgNORs counts may be associated with aggressive biological behaviour but this it not an absolute marker of malignancy in the breast. PMID- 1610762 TI - The lung in tropical eosinophilia compared to that in pulmonary hypertension. Fine structural basis of respiratory disability. AB - Light and electronmicroscopic changes in lung biopsies were studied in six patients with tropical pulmonary eosinophilia, aged 20 to 37 years, of varying duration, and with severe haematologic (blood eosinophil count of 3,600 to 18,200 per mm3), and respiratory changes. On light microscopy the main pathologic reaction consisted of large mononuclear cells and eosinophils in and around the alveoli and blood vessels, and proliferated reticulin. Fine structural changes probably being described for the first time, included the presence of many alveolar macrophages characterised by abundant cytoplasm, irregular or stunted microvilli, increased phagolysosomes with ingested debris, and depletion of other organelles. Eosinophils bearing typical old and young granules, were encountered in and around the alveoli and blood vessels in all case, and collagenosis around alveolar cells in a few. Subacute pneumonitis producing compression and disorganisation of alveoli and blood vessels, and lack of normal apposition of air and blood spaces, appear responsible for the respiratory disability. The detection of mycobacteria, cocci or chlamydia-like bodies in two specimens and of intranuclear virus-like particles in another, could either indicate secondary infection or have an immunogenic significance, in the absence of detection of filarial elements in any of the specimens. Lung biopsies from two additional patients (aged 13 & 32) who had mitral stenosis probably due to rheumatic heart disease, and secondary pulmonary hypertension, were studied as "control" specimens. Both at light and electronmicroscopy these specimens did not show any eosinophils or neutrophils, and fewer macrophages in the lung parenchyma. In contrast to tropical eosinophilia and, as expected, there was considerably more fibrosis of the lung parenchyma, especially in the alveolar subepithelial region and in the vessel walls. This, together with fibroblasts full of endoplasmic cisterns, noted particularly in the younger patient with shorter duration, probably represented an earlier change in this condition. PMID- 1610763 TI - Immunohistochemical characterization of pigmented villonodular synovitis. AB - Pigmented villonodular synovitis is made up of a variety of cells, including round or oval mononuclear cells, fibroblasts, synovial cells and multinucleated giant cells. The mononuclear cells were found to stain positively with anti lysozyme, anti-alpha-1-antitrypsin, anti-alpha-1-antichymotrypsin and anti fibronectin. Vimentin was detected in fibroblasts and in lining cells of the synovial membrane as well as in cells of acinus-like structures. The multinuclear giant cells contained lysozyme, alpha-1-antitrypsin and alpha-1-antichymotrypsin but no vimentin. PMID- 1610764 TI - Morphometric analysis of the angioarchitecture of the synovial membrane in rheumatoid arthritis and osteoarthritis. AB - Using three different immunohistochemical methods we measured the number of vessels, vessel area and diameter and their form factor in the synovial membrane of 102 patients suffering from different joint disease. The variables were evaluated by means of immunomorphometric analysis. We found UEA (Ulex europeus) immunostaining to be the optimal method for quantification of data characterizing the vasculature of the synovial membrane. Irrespective of causes of the given joint disease, we found increases in the number of vessels, vessel perimeter, vessel area and the product of the number of vessels and vessel area over and against the control group (patients without arthritis). Consequences are discussed regarding local bioavailability of medicaments in the synovial membrane. PMID- 1610765 TI - [The importance of an as yet unknown cell reaction: "RIV." A hypothesis]. AB - The research findings described in this paper led to the definition of a new notion, "Reaction Pattern in Vertebrate Cells" (RiV) and, by means of a hypothesis, made it possible to submit a proposition on RiV valency. The problem is of practical importance, particularly for assessment and control of virus infections and tumour diseases. PMID- 1610766 TI - [Prenatally diagnosed mesenchymal hamartoma of the liver]. AB - Reported in this paper is the case of a female newborn with mesenchymal hamartoma of the liver. High-accuracy ultrasonography diagnostics were applied to the mother admitted for examination for suspicion of fetal hydronephrosis in the 31st week of pregnancy. A 7 x 4 cm compartmental process was delineable in the abdominal region of the foetus and was variably viewed in ultrasonography in cystic or solid form. A girl, 2,650 g in body weight and 47 cm in body length, was delivered by caesarean section in the 35th week of pregnancy. Postnatal nutritional disorders were accompanied with recurrent vomiting. Sonography, computed tomography and scintigraphy were performed, and the prenatally diagnosed process was identified as a cystic growth in the right liver lobe with enclosure of the V. cava inferior. A typical hepatolobectomy was performed on the newborn on her 15th day of age, with the V. cava enclosing part being left unextirpated. Mesenchymal hamartoma of the liver was the histological diagnosis. Only one prenatally diagnosed case of this kind had been known from literature before. PMID- 1610767 TI - [The pathogenesis of pulmonary alveolar proteinosis in chronic pneumoconiosis]. PMID- 1610768 TI - [Pathology of the placenta. X. Syncytial proliferation, calcification, cysts, pigments and metabolic disorders]. AB - Part X of this review is devoted to the remaining pathologico-anatomic patterns which are associated with regressive alterations. Increased syncytial proliferation is the most important aspect within that complex, since it may be a consequence of intervillous and intravillous hypoxia and may thus provide a clue to effects of that kind. Placental calcification may be subdivided by two major groups. The first is relating to "dystrophic" calcification following the same rules in the placenta as it does in other places, in other words, it is calcification of necrotic tissue portions or acidotic areas of decreased circulation. Calcification may just as well occur to particular structures of the placenta, such as the epithelial basal membrane, syncytial proliferations or in walls of vessels. Placental cysts usually are localized at the placental base (in septa), their development being owed to hypoxic events during ontogenesis. They actually are pseudocysts. Placental icterus (along with severe maternal icterus) is macroscopically identifiable with unambiguity. The biliary pigment, histologically, is localized in HOFBAUER cells. Additional reference is made to melanin deposits (in concomitance with congenital giant naevus) and placental alterations in conjunction with rare metabolic disorders. PMID- 1610769 TI - [The problems of early diagnosis of diffuse malignant mesothelioma from the pathologo-anatomic view]. AB - An account is given in this paper of particular problems associated with early detection of mesotheliomatous alterations and differential diagnosis for their distinction from reactive mesothelial cell proliferations. Reference is made, in that context, to pathologico-anatomic experience obtained from postmortem and biopsy samples of human malignant mesotheliomas and animal experiments, following exposure to various asbestos-containing dusts. Diagnoses, such as "premesotheliomatous alteration" or "early mesothelioma", in other words, differentiation between benign and malignant, consequently, appear to be unjustified. PMID- 1610770 TI - Incidence and morphology of liver metastasis from extrahepatic malignancies to cirrhotic livers. AB - Incidence and morphologic pattern of liver metastasis from extrahepatic cancer in cirrhosis were studied in 2162 consecutive autopsies performed during a 12.5 year period. The cirrhotic liver was less frequently affected by metastasis than the noncirrhotic liver (33.3% versus 46.4%). The incidence of extrahepatic malignancies and their hematogenous metastasis was lower (though statistically not significant) in patients with cirrhosis than in patients without cirrhosis (20% versus 32%). Patients with cirrhosis but without cancer died at a younger age (63.5 years) than patients with both cancer and cirrhosis (69.5 years). In cirrhotic livers, metastases from neuroendocrine tumors were predominantly localized within the parenchymal nodules, while nonendocrine carcinomas metastasized to the fibrotic septa. The results suggest (1) that patients with cirrhosis develop less frequently extrahepatic malignancies and hepatic metastasis than patients without cirrhosis, probably because of a shorter life expectancy due to the complications of liver cirrhosis; (2) microscopic localization of metastases in cirrhotic livers depend on tumor type. PMID- 1610771 TI - Metastatic growth of v-fos-induced osteosarcoma, following in vitro cultivation. AB - A tumour cell line was established from a non-metastatic osteosarcoma which had developed in the right femur after infection of a newborn mouse with FBR osteosarcoma virus (FBR MSV). After 20 cell culture passages and injection of the cells into newborn syngeneic mice, the animals developed fibrosarcomas on the site of injection. Metastatic lung tumours were detected in 50% of the mice. Metastatic tumour growth was preferentially observed in the walls of large blood vessels and in subpleural zones. Large areas of the metastatic tumours resembled mature connective tissue. This model of in vitro progression from a primary non metastasizing osteosarcoma to a neoplasm with particular metastatic potency, though with a growth pattern similar to fibromatosis may serve as a useful system to study the different steps of metastatic progression, distinct tropism of invasive cells and fibrous maturation of metastatic tumours. PMID- 1610772 TI - Continuous non-invasive blood pressure monitoring in patients with sleep disorders. AB - Sleep related breathing disorders are of high prevalence and are often associated with essential hypertension. It is therefore necessary to study blood pressure continuously in all patients with sleep related breathing disorders and arterial hypertension as well as in all patients with essential hypertension and suspected sleep apnoea. To investigate the usefulness of a non-invasive continuous volume clamp method during sleep we used this technique in parallel with 130 sleep recordings and performed a validation study of the Finapres instrument on a subgroup where continuous invasive blood pressure recordings were available. Absolute pressure values of Finapres are valid when the position and the movement of the sensor were carefully observed and only appropriate segments of the recordings were taken for further evaluation. The high beat to beat resolution of the systolic and diastolic pressure is the main advantage of this non-invasive technique because it reflects rapid blood pressure variations as they occur in sleep related breathing disorders. This could be investigated only invasively until now. PMID- 1610773 TI - Heart rate and arterial pressure variability in humans during different orthostatic load. AB - The influence of posture on the rhythms in blood pressure, heart rate and respiration was tested by means of spectral analysis in 14 healthy subjects. During squatting, standing and sitting, the finger blood pressure was recorded by the non-invasive Penaz technique together with cardiac intervals and respiratory movements. The power spectra obtained from five-minute samples showed that the respiratory components of cardiac interval and pulse pressure were reduced significantly in standing. Compared to squatting, a significant increase of total power in the medium frequency band (0.05-0.15 Hz) for cardiac interval, diastolic and mean pressure could be detected. PMID- 1610774 TI - Pressure wave cardiography; cardiac diagnosis by means of noninvasive continuous blood pressure record. AB - The pulse pressure (PP) is proportional to the preceding interval (T) because of the restitution of contractility and the Starling mechanism, and is inversely proportional to the pre-preceding interval (T-1) because of potentiation of contractility. The aim of the present paper was to find if this relationship can be used for diagnostic purposes. Blood pressure was noninvasively and continuously recorded for 3 minutes (Penaz method), in 26 healthy subjects, in 13 patients with congestive heart failure (NYHA I,II) and sinusoidal rhythms and in 21 patients with atrial fibrillations. By means of multidimensional regression analysis the coefficient D[T] and D[T-1] were calculated in each subject. D[T] expresses the relative role of the preceding, D[T-1] of the pre-preceding interval. The correlation between PP and T was small in subjects with sinusoidal rhythms. Subjects with particular correlation coefficients between PP and T-1 higher than 0.5 were used for further analysis (18 controls, 7 patients). The difference between D[T-1] in controls (0.30 +/- 0.20) and in patients (0.48 +/- 0.19) was significant (Wilcoxon P less than 0.05). In subjects with atrial fibrillations both D[T] and D[T-1] were higher in decompensated patients (Wilcoxon P less than 0.05). The ratio D[T]/D[T-1] was higher in patients with mitral stenosis than in patients with ischaemic heart disease (t-test, P less than 0.05). The test can be usefully employed as a screening test in medical practice. PMID- 1610775 TI - Noninvasive determination of baroreflex sensitivity in man by means of spectral analysis. AB - The spectral analysis technique was applied for noninvasive assessment of heart rate baroreflex sensitivity (BRS). The coherence between fluctuation of blood pressure and heart rate at 0.1 Hz and at respiratory frequency is high. This fact enables the assessment of BRS by means of calculating the modulus (or gain) of the transfer function between variations in blood pressure and heart rate. The noninvasive continuous blood pressure registration according to Penaz was used. During voluntarily controlled breathing intervals, the amplitude of 0.1 Hz and respiratory peaks in the spectra of heart rate and blood pressure changed markedly. Nevertheless, the average sensitivity of the baroreflex (modulus) changed insignificantly. This result indicated that the stability of BRS can be advantageous for the use of BRS in clinical practice. The difference between the modulus at 0.1 Hz and at the breathing rate indicates that baroreflex is only one of the factors causing respiratory arrhythmia. We also compared the determination of BRS by spectral analysis with the following alternative method: both lower extremities were occluded for 5 minutes. The release of pressure in the occluding cuffs decreased blood pressure which was followed by a baroreceptor-mediated increase of heart rate. Both methods correlated, but more detailed analysis revealed the role of the low pressure receptors in BRS determined by spectral analysis. PMID- 1610776 TI - Vasopressin in thermoregulation--competitive demands: experimental evidence and theoretical considerations. AB - Previous studies have substantiated the antipyretic role played by extrahypothalamic limbic system (EXHY-LS) AVP during fever. Repeated attempts to elucidate other thermoregulatory functions of this hormone have failed. Circumstantial evidence, however, suggest central role for this hormone in thermoregulation under hypohydration. Hypohydration, hyperosmolarity and hypovolaemia induced upward shifts in temperature thresholds for activation of heat dissipating mechanisms. When hypovolaemia is superimposed on hyperosmolarity these shifts are additive. Analogously, these two stressors when combined, decrease the osmotic threshold for AVP release. In rats, the elevated temperature thresholds for evaporative cooling and peripheral vasodilation occurring with hypohydration are positively correlated with lower Hypothalamic/EXHY-LS AVP ratio. Reciprocal relations between limbic system and blood AVP contents suggest competitive interaction between central and peripheral demands. Hypothesis for the possible mode of action of central AVP in thermoregulation under hypohydration is discussed. PMID- 1610777 TI - Symposium on Modulation of Body Temperature Control by Humoral Substances. Regional meeting of the International Union of Physiological Sciences. Prague, July 1-5, 1991. PMID- 1610778 TI - Evidence for antipyretic vasopressinergic pathways and their modulation by noradrenergic afferents. AB - The experimental evidence for the antipyretic action of arginine vasopressin (AVP) in guinea-pigs can be summarized as follows: The febrile response to a bacterial pyrogen can be reduced by a microinfusions of exogenous AVP into the ventral septal area of the limbic system. Immunohistochemical studies indicate increased activity of AVP terminals in the ventral septal area (VSA) and in parvocellular AVP neurones of the hypothalamic paraventricular nucleus (PVN) in several stressful situations accompanied by reduced febrile responses (late stage of pregnancy, immobilization, cold adaptation, osmotic stimulation). Also the peripheral and/or central release of AVP measured in some of these situations is increased. Electrical stimulation of the PVN suppresses fever, this suppression can, at least partly, be cancelled by simultaneous intraseptal application of the vasopressinergic V1 receptor antagonist. The documented AVP pathways from the PVN to the septum receive noradrenergic afferents from the lower brainstem. Chronic destruction of these afferents by microinjections of 6-hydroxydopamine (6-OHDA) significantly reduced the fever responses to pyrogen application, while microinfusion of noradrenaline (NA) enhances the fever reaction. PMID- 1610779 TI - Criteria for set point estimation in the volume clamp method of blood pressure measurement. AB - When blood pressure is measured in the finger using the volume clamp method the value at which the vascular volume is clamped is of crucial importance. Since the discovery of the method, several criteria of finding a correct set point have been elaborated: 1. The volume oscillations reach their maximum amplitude at cuff pressure equalling mean blood pressure. 2. The form of the diastolic portion of volume pulsations changes if the cuff pressure moves around the mean blood pressure. 3. The set point can be positioned at one third of the arterial volume. 4. The dynamic vascular compliance (DVC) may be continuously measured as the instantaneous amplitude of vascular volume oscillations is elicited by a relatively small and rapid vibration of the cuff pressure. The shape of the DVC pulse characteristically depends on the transmural pressure (TP): at negative TP (cuff pressure exceeding the blood pressure) it shows a distinct positive systolic peak, at positive TP the polarity of the DVC pulse is reversed. In contrast to the first three ways to find the set point, the last one may operate even in closed-loop performance, i.e. during the blood pressure measurement. PMID- 1610780 TI - Quantitative aspects of the fever response elicited by intracerebral injection of endotoxin in the guinea-pig. AB - Fever developing after intracerebral injections of lipopolysaccharide (LPS) to guinea-pigs were monophasic, with only one peak of inner body temperature slowly developing and longlasting in a dose range 20 to 200 ng of LPS. Latency time was inversely related to the dose of LPS. Indomethacin injected to the third brain ventricle did not abolish fever response. PMID- 1610781 TI - The role of serotonergic system in body temperature regulation. AB - Results indicate that vascular responses to temperature stimulation are predominantly impaired in animals with 5-HT deprivation. A hypothesis is therefore raised that the 5-HT system participates in body temperature regulation in such a way as to link the regulatory output with vasomotor pathways. The 5-HT system in the spinal cord has been shown to inhibit the afferent transmission of temperature signals. Therefore, depletion of 5-HT does not prevent sensory transmission, at least at the spinal cord level. PMID- 1610782 TI - Modulation of cutaneous cold receptor function by electrolytes, hormones and thermal adaptation. AB - The response properties of feline cold receptors were analyzed under control conditions, during conditions of altered external calcium concentrations and during application of menthol, catecholamines and ouabain. Afferent activity was extracellularly recorded from cold fibres of an isolated preparation of the tongue. Reduced calcium levels (0.5 mM) generally enhanced and elevated calcium levels (5.0 mM) suppressed cold fibre activity. The effects of menthol (10(-5) M) on cold receptors were qualitatively similar to those of reduced calcium. Application of adrenaline and noradrenaline (10(-6) M) were predominantly inhibiting. In cold receptors, the mean discharge rate is determined by the frequency of an oscillating receptor process and the probability of each cycle of this process to initiate afferent impulses. All measures mainly affected the probability of impulse generation rather than the oscillation frequency. Application of ouabain (10(-6) M) resulted in excitatory responses, caused by an increase of both probability of impulse generation and frequency of the oscillating receptor process. It is concluded that cold receptor function is based on a specific combination of common neuronal elements rather than on specific sensory processes. PMID- 1610783 TI - Properties of hypothalamic temperature sensitive and insensitive neurones. AB - Intracellular recordings show that some hypothalamic neurones are inherently warm sensitive and have branching dendrites that allow synaptic integration of different afferent pathways. PMID- 1610784 TI - The effect of PGE2 on activity and thermosensitivity of hypothalamic neurones in rat brain slices. AB - Using brain slices the effect of prostaglandin E2 (PGE2) on neurones from different locations of the rat hypothalamus was analysed. PGE2 (150 ng), when injected into the perfusion chamber, influences all hypothalamic neurones studied. The pattern of firing rate changes after PGE2 is variable, but the depressive effect predominates--72% of neurones decrease their firing rate in long-term experiments. PGE2 also lowers the thermosensitivity of warm sensitive neurones and increases the thermosensitivity of temperature insensitive neurones. PMID- 1610785 TI - Does the effect of AVP on hypothalamic neurones support its proposed role in endogenous antipyresis? AB - The effect of AVP on unit activity and temperature sensitivity was tested in hypothalamic slices of the rat. The results demonstrate that AH/PO neurones in vitro react to AVP by significant changes of both static discharge and temperature sensitivity supporting the idea of direct modulation of thermoregulatory neurones by AVP. PMID- 1610786 TI - Burst activity and synaptic mechanisms in a hypothalamic network grown in culture. AB - In a cultured network of rat embryonic hypothalamic cells, synaptic interaction is through GABAA-receptors, that mediate inhibition by an increase in Cl- conductance, and AMPA-receptors, that mediate excitation by an increase in monovalent cationic conductance. Changes in the balance of inhibition and excitation towards a predominance of excitation lead to phasic synchronous activity of the cells. Synaptic interaction through these receptors is thus capable of modulating neurosecretion rapidly. PMID- 1610788 TI - Thermoregulation in infant rats. PMID- 1610787 TI - Osmoreception in the duck's brain identified by neurophysiological methods and phylogenetic structural cues. AB - Central nervous thermo- and osmo-responsive neurones are considered as important signal generators in the corresponding homeostatic control systems. Criteria for specificity are discussed in view of only functional evidence for the former, and of both functional and structural evidence for the latter. PMID- 1610789 TI - Molecular characterization of two galactosemia mutations and one polymorphism: implications for structure-function analysis of human galactose-1-phosphate uridyltransferase. AB - We report here the molecular characterization of two galactosemia mutations, L74P and F171S, and one polymorphism, S135L, in human galactose-1-phosphate uridyltransferase (GALT). Both galactosemia mutations result in reduced enzymatic activity when reconstructed in the cDNA and overexpressed. The polymorphism, in contrast, has near normal activity. Both mutations affect evolutionarily conserved residues, suggesting that they are functionally important, while the polymorphism occurs in a nonconserved domain which is presumably not critical for enzymatic function. The F171S mutation is close to the putative active-site nucleophile. Our data further support the notion of molecular heterogeneity of galactosemia and suggest that galactosemia mutations and GALT polymorphisms may be useful tools in highlighting different functional domains in human GALT. PMID- 1610790 TI - Gonadotropin releasing hormone activates the lipoxygenase pathway in cultured pituitary cells: role in gonadotropin secretion and evidence for a novel autocrine/paracrine loop. AB - The formation and role of arachidonic acid (AA) and its metabolites during gonadotropin releasing hormone- (GnRH-) induced gonadotropin secretion were investigated in primary cultures of rat pituitary cells. Prelabeled cells ([3H]AA) responded to GnRH challenge with increased formation (about 2-fold) of the leukotrienes LTC4, LTD4, and LTE4 as well as 5- and 15-eicosatetraenoic acids (5- and 15-HETE) as identified by HPLC. Formation of leukotrienes and 15-HETE was further verified by specific radioimmunoassays. No significant increase in the formation of 12-HETE or of the cyclooxygenase products prostaglandin E (PGE) and thromboxane A2 by GnRH was noticed. Addition of physiological concentrations of LTC4 enhanced basal LH release, while subphysiological concentrations of LTC4 (10(-15)-10(-12) M) inhibited GnRH-induced LH release by about 35% (p less than 0.02). Using specific lipoxygenase inhibitors L-656,224 and MK 886, we found inhibition of GnRH-induced LH release by about 40% at concentrations known to specifically inhibit the 5-lipoxygenase pathway. The peptidoleukotriene receptor antagonist ICI 198,615 inhibited LTC4- and LTE4-induced LH release and surprisingly also the effect of GnRH on LH release by 40%. The data strongly suggest a role for AA and its lipoxygenase metabolites in the on/off reactions of GnRH upon LH release. The data also present a novel amplification cycle in which newly formed leukotrienes become first messengers and establish an autocrine/paracrine loop. PMID- 1610791 TI - Protein engineering of xylose (glucose) isomerase from Actinoplanes missouriensis. 1. Crystallography and site-directed mutagenesis of metal binding sites. AB - The structure and function of the xylose (glucose) isomerase from Actinoplanes missouriensis have been analyzed by X-ray crystallography and site-directed mutagenesis after cloning and overexpression in Escherichia coli. The crystal structure of wild-type enzyme has been refined to an R factor of 15.2% against diffraction data to 2.2-A resolution. The structures of a number of binary and ternary complexes involving wild-type and mutant enzymes, the divalent cations Mg2+, Co2+, or Mn2+, and either the substrate xylose or substrate analogs have also been determined and refined to comparable R factors. Two metal sites are identified. Metal site 1 is four-coordinated and tetrahedral in the absence of substrate and is six-coordinated and octahedral in its presence; the O2 and O4 atoms of linear inhibitors and substrate bind to metal 1. Metal site 2 is octahedral in all cases; its position changes by 0.7 A when it binds O1 of the substrate and by more than 1 A when it also binds O2; these bonds replace bonds to carboxylate ligands from the protein. Side chains involved in metal binding have been substituted by site-directed mutagenesis. The biochemical properties of the mutant enzymes are presented. Together with structural data, they demonstrate that the two metal ions play an essential part in binding substrates, in stabilizing their open form, and in catalyzing hydride transfer between the C1 and C2 positions. PMID- 1610792 TI - Protein engineering of xylose (glucose) isomerase from Actinoplanes missouriensis. 2. Site-directed mutagenesis of the xylose binding site. AB - Site-directed mutagenesis in the active site of xylose isomerase derived from Actinoplanes missouriensis is used to investigate the structural and functional role of specific residues. The mutagenesis work together with the crystallographic studies presented in detail in two accompanying papers adds significantly to the understanding of the catalytic mechanism of this enzyme. Changes caused by introduced mutations emphasize the correlation between substrate specificity and cation preference. Mutations in both His 220 and His 54 mainly affect the catalytic rate constant, with catalysis being severely reduced but not abolished, suggesting that both histidines are important, but not essential, for catalysis. Our results thus challenge the hypothesis that His 54 acts as an obligatory catalytic base for ring opening; this residue appears instead to be implicated in governing the anomeric specificity. With none of the active site histidines acting as a catalytic base, the role of the cations in catalyzing proton transfer is confirmed. In addition, Lys 183 appears to play a crucial part in the isomerization step, by assisting the proton shuttle. Other residues also are important but to a lesser extent. The conserved Lys 294 is indirectly involved in binding the activating cations. Among the active site aromatic residues, the tryptophans (16 and 137) play a role in maintaining the general architecture of the substrate binding site while the role of Phe 26 seems to be purely structural. PMID- 1610793 TI - Protein engineering of xylose (glucose) isomerase from Actinoplanes missouriensis. 3. Changing metal specificity and the pH profile by site-directed mutagenesis. AB - Aldose-ketose isomerization by xylose isomerase requires bivalent cations such as Mg2+, Mn2+, or Co2+. The active site of the enzyme from Actinoplanes missouriensis contains two metal ions that are involved in substrate binding and in catalyzing a hydride shift between the C1 and C2 substrate atoms. Glu 186 is a conserved residue located near the active site but not in contact with the substrate and not with a metal ligand. The E186D and E186Q mutant enzymes were prepared. Both are active, and their metal specificity is different from that of the wild type. The E186Q enzyme is most active with Mn2+ and has a drastically shifted pH optimum. The X-ray analysis of E186Q was performed in the presence of xylose and either Mn2+ or Mg2+. The Mn2+ structure is essentially identical to that of the wild type. In the presence of Mg2+, the carboxylate group of residue Asp 255, which is part of metal site 2 and a metal ligand, turns toward Gln 186 and hydrogen bonds to its side-chain amide. Mg2+ is not bound at metal site 2, explaining the low activity of the mutant with this cation. Movements of Asp 255 also occur in the wild-type enzyme. We propose that they play a role in the O1 to O2 proton relay accompanying the hydride shift. PMID- 1610794 TI - Enzyme-catalyzed oxidation of cholesterol in mixed phospholipid monolayers reveals the stoichiometry at which free cholesterol clusters disappear. AB - In this study, we have used cholesterol oxidase as a probe to study cholesterol/phospholipid interactions in mixed monolayers at the air/water interface. Mixed monolayers, containing a single phospholipid class and cholesterol at differing cholesterol/phospholipid molar ratios, were exposed to cholesterol oxidase at a lateral surface pressure of 20 mN/m (at 22 degrees C). At equimolar ratios of cholesterol to phospholipid, the average rate of cholesterol oxidation was fastest in unsaturated phosphatidylcholine mixed monolayers (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine and egg yolk phosphatidylcholine), intermediate in 1,2-dipalmitoyl-sn-glycero-3 phosphocholine, and slowest in sphingomyelin monolayers (egg yolk or bovine brain sphingomyelin). The average oxidation rate in mixed monolayers was not exclusively a function of monolayer packing density, since egg yolk and bovine brain sphingomyelin mixed monolayers occupied similar mean molecular areas even though the measured average oxidation rate was different with these two phospholipids. This suggests that the phospholipid acyl chain composition influenced the oxidation rate. The importance of the phospholipid acyl chain length on influencing the average oxidation rate was further examined in defined phosphatidylcholine mixed monolayers. The average oxidation rate decreased linearly with increasing acyl chain lengths (from di-8:0 to di-18:0). When the average oxidation rate was examined as a function of the cholesterol to phospholipid (C/PL) molar ratio in the monolayer, the otherwise linear function displayed a clear break at a 1:1 stoichiometry with phosphatidylcholine mixed monolayers, and at a 2:1 C/PL stoichiometry with sphingomyelin mixed monolayers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610795 TI - How fast does an acetylcholine receptor channel open? Laser-pulse photolysis of an inactive precursor of carbamoylcholine in the microsecond time region with BC3H1 cells. AB - The integrated function of the nervous system depends on specific and rapid transmission of signals between its constituent cells. The nicotinic acetylcholine receptor is the best known of a group of membrane-bound proteins responsible for such transmission; for this process to occur, a specific neurotransmitter, in this case acetylcholine, must bind to the receptor, which then forms transmembrane channels through which cations pass. The resulting change in transmembrane voltage determines whether or not a signal is transmitted. The question of how fast this process takes place in any neurotransmitter receptor has remained one of the interesting and most challenging in the field. To answer it, many attempts have been made to evaluate the rate constant for the opening of the acetylcholine receptor channel, but in almost all these studies the rate was measured after the receptor-mediated reaction, which involves the open channel and many intermediate states, had reached a quasi equilibrium. This resulted in a plethora of reported values for the rate constant that differ by a factor of up to 50-fold, even when the measurements were made with the same type of cell. The new approach described here involves the use of single cells of a mammalian cell line (BC3H1), containing muscle-type acetylcholine receptors, and the rapid introduction of neurotransmitter to the cell surface. The rapid delivery was achieved by converting a previously synthesized photolabile precursor of carbamoylcholine to carbamoylcholine, a stable amino-group-containing analogue of acetylcholine, with a single laser pulse and an observed photolysis rate of 7300 s-1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610796 TI - Mechanics of solute translocation catalyzed by enzyme IImtl of the phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli. AB - The kinetics of binding of mannitol to enzyme IImtl embedded in the membrane of vesicles with an inside-out or a right-side-out orientation were analyzed at 4 degrees C in the absence of the phosphoryl group donor, P-HPr. The binding to the right-side-out oriented vesicles equilibrated too fast to be monitored by the flow dialysis technique. On the other hand, with the inside-out oriented membrane vesicles two conformational changes of the enzyme could be detected kinetically. One change involved a recruitment of binding sites from a state of the enzyme where the binding sites were inaccessible from the cytoplasmic volume. The second change involved a conformational change of the enzyme that followed upon the initial binding to the cytoplasmic-facing binding site leading to a state with a higher affinity for mannitol. Equilibrium binding to the inside-out and right side-out oriented membrane vesicles at 4 degrees C indicated that the two transitions did not represent the translocation of the binding site, free and with mannitol bound to it, to the other side of the membrane. Instead, a model is proposed in which the conformational changes represent transitions from states with the binding pocket opened to the cytoplasmic side of the membrane to occluded states of the enzyme in which the binding sites, with or without mannitol bound, are not accessible to either side of the membrane. PMID- 1610797 TI - Affinity labeling of human placental 3 beta-hydroxy-delta 5-steroid dehydrogenase and steroid delta-isomerase: evidence for bifunctional catalysis by a different conformation of the same protein for each enzyme activity. AB - 3 beta-Hydroxy-delta 5-steroid dehydrogenase and steroid delta-isomerase copurify from human placental microsomes as a single enzyme protein. The affinity alkylating secosteroid, 5,10-secoestr-4-yne-3,10,17-trione, inactivates the dehydrogenase and isomerase reactions in a time-dependent manner, but which of the two activities is targeted depends on the concentration of secosteroid. At 2 5 microM secosteroid, the dehydrogenase activity is alkylated in a site-specific manner (pregnenolone slows inactivation) that follows first-order inactivation kinetics (KI = 4.2 microM, k3 = 1.31 x 10(-2) min-1). As the secosteroid level increases from 11 to 30 microM, dehydrogenase is paradoxically inactivated at progressively slower rates, and pregnenolone no longer protects against the alkylator. The inactivation of isomerase exhibits the expected first-order kinetics (KI = 31.3 microM, k3 = 6.42 x 10(-2) min-1) at 11-30 microM secosteroid. 5-Androstene-3,17-dione protects isomerase from inactivation by 15 microM secosteroid, but the substrate steroid unexpectedly fails to slow the inactivation of isomerase by a lower concentration of alkylator (5 microM). A shift from a dehydrogenase to an isomerase conformation in response to rising secosteroid levels explains these results. Analysis of the ligand-induced conformational change along with cofactor protection data suggests that the enzyme expresses both activities at a bifunctional catalytic site. According to this model, the protein begins the reaction sequence as 3 beta-hydroxysteroid dehydrogenase. The products of the first step (principally NADH) promote a change in protein conformation that triggers the isomerase reaction. PMID- 1610798 TI - EPSP synthase: binding studies using isothermal titration microcalorimetry and equilibrium dialysis and their implications for ligand recognition and kinetic mechanism. AB - Isothermal titration calorimetry measurements are reported which give important new binding constant (Kd) information for various substrate and inhibitor complexes of Escherichia coli EPSP synthase (EPSPS). The validity of this technique was first verified by determining Kd's for the known binary complex with the substrate, shikimate 3-phosphate (S3P), as well as the herbicidal ternary complex with S3P and glyphosate (EPSPS.S3P.glyphosate). The observed Kd's agreed very well with those from previous independently determined kinetic and fluorescence binding measurements. Further applications unequivocally demonstrate for the first time a fairly tight interaction between phosphoenolpyruvate (PEP) and free enzyme (Kd = 390 microM) as well as a correspondingly weak affinity for glyphosate (Kd = 12 mM) alone with enzyme. The formation of the EPSPS.PEP binary complex was independently corroborated using equilibrium dialysis. These results strongly suggest that S3P synergizes glyphosate binding much more effectively than it does PEP binding. These observations add important new evidence to support the hypothesis that glyphosate acts as a transition-state analogue of PEP. However, the formation of a catalytically productive PEP binary complex is inconsistent with the previously reported compulsory binding order process required for catalysis and has led to new studies which completely revise the overall EPSPS kinetic mechanism. A previously postulated ternary complex between S3P and inorganic phosphate (EPSPS.S3P.Pi, Kd = 4 mM) was also detected for the first time. Quantitative binding enthalpies and entropies were also determined for each ligand complex from the microcalorimetry data. These values demonstrate a clear difference in thermodynamic parameters for recognition at the S3P site versus those observed for the PEP, Pi, and glyphosate sites. PMID- 1610799 TI - Multiple role of hydrophobicity of tryptophan-108 in chicken lysozyme: structural stability, saccharide binding ability, and abnormal pKa of glutamic acid-35. AB - Trp108 of chicken lysozyme is in van der Waals contact with Glu35, one of two catalytic carboxyl groups. The role of Trp108 in lysozyme function and stability was investigated by using mutant lysozymes secreted from yeast. By the replacement of Trp108 with less hydrophobic residues, Tyr (W108Y lysozyme) and Gln (W108Q lysozyme), the activity, saccharide binding ability, stability, and pKa of Glu35 were all decreased with a decrease in the hydrophobicity of residue 108. Namely, at pH 5.5 and 40 degrees C, the activities of W108Y and W108Q lysozymes against glycol chitin were 17.3 and 1.6% of that of wild-type lysozyme, and their dissociation constants for the binding of a trimer of N-acetyl-D glucosamine were 7.4 and 309 times larger than that of wild-type lysozyme, respectively. For the reversible unfolding at pH 3.5 and 30 degrees C, W108Y and W108Q lysozymes were less stable than wild-type lysozyme by 1.4 and 3.6 kcal/mol, respectively. As for the pKa of Glu35, the values for W108Y and W108Q lysozymes were found to be lower than that for wild-type lysozyme by 0.2 and by 0.6 pKa unit, respectively. The pKa of Glu35 in lysozyme was also decreased from 6.1 to 5.4 by the presence of 1-3 M guanidine hydrochloride, or to 5.5 by the substitution of Asn for Asp52, another catalytic carboxyl group. Thus, both the hydrophobicity of Trp108 and the electrostatic interaction with Asp52 are equally responsible for the abnormally high pKa (6.1) of Glu35, compared with that (4.4) of a normal glutamic acid residue.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610800 TI - A hybrid ribulosebisphosphate carboxylase/oxygenase enzyme exhibiting a substantial increase in substrate specificity factor. AB - Two hybrid ribulose-1,5 bisphosphate carboxylase/oxygenase (RubisCO) enzymes were constructed using RubisCO small subunit genes (rbcS) from two eucaryotic marine organisms, Cylindrotheca sp. N1 and Olisthodiscus luteus, cloned downstream of the RubisCO large subunit gene (rbcL) of the cyanobacterium Synechococcus PCC 6301. The expression products synthesized by Escherichia coli JM107 (pVTAC223 and pANOLI) were purified and examined by polyacrylamide gel electrophoresis and compared to the purified products generated by E. coli MV1190 (pBGL710), containing cyanobacterial rbcL and rbcS genes. Both Cylindrotheca and Olisthodiscus small subunits were able to assemble in vivo with the Synechococcus large subunit octamer to form heterologous hexadecameric L8S8 enzymes, the pVTAC223 and pANOLI hybrid enzymes, respectively. Like the Synechococcus RubisCO, the hybrid enzymes were rapidly activated by Mg2+ plus HCO3-, even in the presence of RuBP. The hybrid enzymes, however, were considerably more sensitive to the competitive inhibitor 6-phosphogluconate. Detailed kinetic analysis indicated that while the carboxylase activity of both chimeric enzymes was severely reduced, in the case of the pVTAC223 hybrid enzyme, the degree of partitioning between carboxylation and oxygenation was increased nearly 60% relative to the Synechococcus RubisCO. Other kinetic properties, including the Michaelis constants for the gaseous substrates and RuBP, were altered in the hybrid proteins. These studies also led to the finding that the substrate specificity factor of the Cylindrotheca RubisCO is unusually high. PMID- 1610802 TI - Picosecond dynamics of bacteriorhodopsin, probed by time-resolved infrared spectroscopy. AB - The photoinduced reaction cycle of bacteriorhodopsin (BR) has been studied by means of a recently developed picosecond infrared spectroscopic method at ambient temperature. BR - K difference spectra between 1560 and 1700 cm-1 have been recorded at delay times from 100 ps to 14 ns. The spectrum remains unchanged during this period. The negative difference OD band at 1660 cm-1 indicates the peptide backbone responds within 50 ps. A survey in the region of carboxylic side chain absorption around 1740 cm-1 reveals that perturbations of those groups, present in low-temperature FTIR spectra, are not observable within 10 ns, suggesting a slow conformational change. PMID- 1610801 TI - Analysis of the two-state behavior of the thermal unfolding serum retinol binding protein containing a single retinol ligand. AB - Through the use of CD and DSC, the thermal unfolding of holo serum retinol binding protein containing a single, tightly bound retinol ligand was studied at pH 7.4. The DSC endotherm of the holoprotein ([retinol]/[protein] = 1) was asymmetric about the transition temperature of 78 degrees C. Using changes in ellipticity at 230 nm, the thermal unfolding curve was also asymmetric about the inflection point centered near 78 degrees C. van't Hoff enthalpies were determined by three means and compared to the calorimetric enthalpy (delta Hcal) of 200 kcal/mol. A van't Hoff enthalpy of 190 kcal/mol was determined from the dependence of transition temperature on the concentration of the ligand-bound protein. This value agreed well with the van't Hoff enthalpies found from fits of the DSC (delta HvH = 184 kcal/mol) and spectroscopic (delta HvH = 181 kcal/mol) curves to a two-state thermodynamic model that included ligand dissociation (NR in equilibrium with U+R, where NR is the native holoprotein, U is the unfolded apoprotein, and R is retinol). Poor agreement was obtained with a two-state model that ignored ligand dissociation (N in equilibrium with U). Furthermore, the NR in equilibrium with U+R model accounted for the asymmetry in both CD and DSC transitions and yielded a much improved fit of the data over the N in equilibrium with U model. From these considerations and simulations on other equilibrium models, it is suggested that the NR in equilibrium with U+R model is the simplest model that describes the thermal unfolding of this ligand-bound protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610803 TI - Identification of an isoprenylated cysteine methyl ester hydrolase activity in bovine rod outer segment membranes. AB - Proteins from eucaryotic cells which have a carboxyl-terminal CAAX motif are posttranslationally modified by isoprenylation. The pathway involves the linkage of an all-trans-farnesyl (C15) or an all-trans-geranylgeranyl (C20) moiety to the cysteine residue followed by proteolysis which generates the modified cysteine as the carboxyl-terminal residue. Carboxylmethylation of the modified cysteine residue completes the pathway. This latter methylation reaction is the only potentially reversible reaction in the pathway and thus of possible regulatory significance. A specific esterase is required to reverse the methylation. It is demonstrated here that simple isoprenylated cysteine derivatives, such as N acetyl-S-farnesyl-L-cysteine methyl ester (L-AFCM) and N-acetyl-S-geranylgeranyl L-cysteine methyl ester (L-AGGCM), are substrates for a rod outer segment (ROS) membrane esterase activity. The KM and Vmax values for L-AFCM and L-AGGCM are 186 microM and 2.2 nmol mg-1 min-1 and 435 microM and 4.8 nmol mg-1 min-1, respectively. The enzyme(s) is stereoselective rather than stereospecific because D-AFCM is enzymatically hydrolyzed with KM and Vmax values of 157 microM and 0.46 nmol mg-1 min-1, respectively. The enzyme(s) does not process N-acetyl-L-cysteine methyl ester, demonstrating that the isoprenyl moiety is required for substrate activity. Ebelactone B is a potent mechanism-based inactivator of the enzyme with a KI = 42 microM and a kinh = 3.7 x 10(-3) s-1. Importantly, L-AFCM, L-AGGCM, and ebelactone B all inhibit the demethylation of the endogenous ROS substrates, showing that the same enzymatic activity is involved in the processing of the synthetic and physiological substrates. PMID- 1610804 TI - The secondary structure of the colicin E3 immunity protein as studied by 1H-1H and 1H-15N two-dimensional NMR spectroscopy. AB - By performing 1H-1H and 1H-15N two-dimensional (2D) nuclear magnetic resonance (NMR) experiments, the complete sequence-specific resonance assignment was determined for the colicin E3 immunity protein (84 residues; ImmE3), which binds to colicin E3 and inhibits its RNase activity. First, the fingerprint region of the spectrum was analyzed by homonuclear 1H-1H HOHAHA and NOESY methods. For the identification of overlapping resonances, heteronuclear 1H-15N (HMQC-HOHAHA, HMQC NOESY) experiments were performed, so that the complete 1H and 15N resonance assignments were provided. Then the secondary structure of ImmE3 was determined by examination of characteristic patterns of sequential backbone proton NOEs in combination with measurement of exchange rates of amide protons and 3JHN alpha coupling constants. From these results, it was concluded that ImmE3 contains a four-stranded antiparallel beta-sheet (residues 2-10, 19-22, 47-49, and 71-79) and a short alpha-helix (residues 31-36). PMID- 1610805 TI - Fluorenyl fatty acids as fluorescent probes for depth-dependent analysis of artificial and natural membranes. AB - The main objective of depth-dependent fluorescent probes is to provide information at a distinct position in the membrane hydrophobic core. We report here a series of fluorenyl fatty acids which can probe both artificial and natural membranes at different depths. Long-chain acids (C4, C6, and C8) are attached to fluorene chromophore on one side, and a hydrophobic tail (C4) is attached on the other side, so that on incorporation in membranes the carboxyl end of the molecule is oriented toward the membrane-water interface and the hydrophobic tail points toward the membrane interior. These acids can be readily partitioned into membranes. The disposition of these fluorenyl fatty acids in membranes was studied by fluorescence quenching using iodide as a water-soluble and 9,10-dibromostearic acid as a lipid-soluble quencher. The results obtained indicate that attachment of a hydrophobic tail is essential for effective alignment of depth-dependent fluorescent probes. The length of the hydrophobic tail was varied and an n-butyl chain was found to be most effective. In all cases, the compounds with a hydrophobic tail were found to be probing the membrane deeper than their counterparts with no hydrophobic tail. Further, the compounds with hydrophobic tails were more strongly immobilized in the membrane as indicated by fluorescence polarization studies. However, the effect of such a tail varied with membrane type. Thus in artificial membranes an n-butyl chain was found to be extremely important for effective monitoring by shallow probes like 4 (2'-fluorenyl)butyric acid, whereas in erythrocyte ghost membranes the same n butyl tail was found to be more desirable for deeper probes like 8-(2' fluorenyl)octanoic acid.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610806 TI - Isolation and characterization of the three polypeptide components of 4 chlorobenzoate dehalogenase from Pseudomonas sp. strain CBS-3. AB - The three genes encoding the 4-chlorobenzene dehalogenase polypeptides were excised from a Pseudomonas sp. CBS-3 DNA fragment and separately cloned and expressed in Escherichia coli. The three enzymes were purified from the respective subclones by using an ammonium sulfate precipitation step followed by one or two column chromatographic steps. The 4-chlorobenzoate:coenzyme A ligase was found to be a homodimer (57-kDa subunit size), to require Mg2+ (Co2+ and Mn2+ are also activators) for activity, and to turn over MgATP (Km = 100 microM), coenzyme A (Km = 80 microM), and 4-chlorobenzoate (Km = 9 microM) at a rate of 30 s-1 at pH 7.5 and 25 degrees C. Benzoate, 4-bromobenzoate, 4-iodobenzoate, and 4 methylbenzoate were shown to be alternate substrates while 4-hydroxybenzoate, 4 aminobenzoate, 2-aminobenzoate, 2,3-dihydroxybenzoate, 4-coumarate, palmate, laurate, caproate, butyrate, and phenylacetate were not substrate active. The 4 chlorobenzoate-coenzyme A dehalogenase was found to be a homotetramer (30 kDa subunit size) to have a Km = 15 microM and kcat = 0.3 s-1 at pH 7.5 and 25 degrees C and to be catalytically inactive toward hydration of crotonyl-CoA, alpha-methylcrotonyl-CoA, and beta-methylcrotonyl-CoA. The 4-hydroxybenzoate coenzyme A thioesterase was shown to be a homotetramer (16 kDa subunit size), to have a Km = 5 microM and kcat = 7 s-1 at pH 7.5 and 25 degrees C, and to also catalyze the hydrolyses of benzoyl-coenzyme A and 4-chlorobenzoate-coenzyme A. Acetyl-coenzyme A, hexanoyl-coenzyme A, and palmitoyl-coenzyme A were not hydrolyzed by the thioesterase. PMID- 1610807 TI - Interaction of flexible analogs of N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and of N-methyl-4-phenylpyridinium with highly purified monoamine oxidase A and B. AB - Sixteen analogs of N-methyl-1,2,3,6-tetrahydropyridine (MPTP) of varying degrees of flexibility have been studied as substrates of highly purified monoamine oxidases (MAO) A and B. The relative effectiveness of the various tetrahydropyridines as substrates of MAO A and B were evaluated in terms of the function turnover number/Km, as determined by initial rate measurements. The insertion of a methylene bridge between the phenyl and tetrahydropyridine moieties of MPTP to yield N-methyl-4-benzyl-1,2,3,6-tetrahydropyridine, rendering the molecule more flexible, greatly enhances reactivity with MAO B, but not with MAO A, as compared with MPTP itself, in accord with data in the literature (Youngster et al., 1989a). The ethylene-bridged MPTP analog, on the other hand, is a far better substrate of both forms of MAO than is MPTP itself. The effect of molecular flexibility on the rate of oxidation of these compounds is obscured by substituents on the aromatic ring. Branching and rigidity were detrimental to the activity as substrates of both forms of MAO. Those analogs of 1 which contain small electron-withdrawing substituents in the phenyl ring were found to be more selective for MAO B, while those substituted with bulky groups were selectively oxidized by MAO A. The substrate binding site of MAO A probably contains a lipophilic pocket larger than that found in a similar site in MAO B. PMID- 1610808 TI - Interaction of CPa-1 with the manganese-stabilizing protein of photosystem II: identification of domains cross-linked by 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide. AB - The structural organization of photosystem II proteins has been investigated by use of the zero-length protein cross-linking reagent 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide and monoclonal and polyclonal antibody reagents. Photosystem II membranes were treated with 1-ethyl-3-[3 (dimethylamino)propyl]carbodiimide which cross-links amino groups to carboxyl groups which are in van der Waals contact. This treatment did not affect the oxygen evolution rates of these membranes and increased the retention of oxygen evolution after CaCl2 washing. Analysis of the proteins cross-linked by this treatment indicated that two cross-linked species with apparent molecular masses of 95 and 110 kDa were formed which cross-reacted with antibodies against both the 33-kDa manganese-stabilizing protein and the chlorophyll protein CPa-1. Cleavage of the 110-kDa cross-linked species with cyanogen bromide followed by N terminal sequence analysis was used to identify the peptide fragments of CPa-1 and the manganese-stabilizing protein which were cross-linked. Two cyanogen bromide fragments were identified with apparent molecular masses of 50 and 25 kDa. N-Terminal sequence analysis of the 50-kDa cyanogen bromide fragment indicates that this consists of the C-terminal 16.7-kDa fragment of CPa-1 and the intact manganese-stabilizing protein. This strongly suggests that the manganese stabilizing protein is cross-linked to the large extrinsic loop domain of CPa-1. N-Terminal analysis of the 25-kDa cyanogen bromide fragment indicates that this consists of the C-terminal 16.7-kDa peptide of CPa-1 and the N-terminal 8-kDa peptide of the manganese-stabilizing protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610809 TI - NMR studies of amyloid beta-peptides: proton assignments, secondary structure, and mechanism of an alpha-helix----beta-sheet conversion for a homologous, 28 residue, N-terminal fragment. AB - Beta-peptide is a major component of amyloid deposits in Alzheimer's disease. We report here a proton nuclear magnetic resonance (NMR) spectroscopic investigation of a synthetic peptide that is homologous to residues 1-28 of beta-peptide [abbreviated as beta-(1-28)]. The beta-(1-28) peptide produces insoluble beta pleated sheet structures in vitro, similar to the beta-pleated sheet structures of beta-peptide in amyloid deposits in vivo. For peptide solutions in the millimolar range, in aqueous solution at pH 1-4 the beta-(1-28) peptide adopts a monomeric random coil structure, and at pH 4-7 the peptide rapidly precipitates from solution as an oligomeric beta-sheet structure, analogous to amyloid deposition in vivo. The NMR work shown here demonstrates that the beta-(1-28) peptide can adopt a monomeric alpha-helical conformation in aqueous trifluoroethanol solution at pH 1-4. Assignment of the complete proton NMR spectrum and the determination of the secondary structure were arrived at from interpretation of two-dimensional (2D) NMR data, primarily (1) nuclear Overhauser enhancement (NOE), (2) vicinal coupling constants between the amide (NH) and alpha H protons, and (3) temperature coefficients of the NH chemical shifts. The results show that at pH 1.0 and 10 degrees C the beta-(1-28) peptide adopts an alpha-helical structure that spans the entire primary sequence. With increasing temperature and pH, the alpha-helix unfolds to produce two alpha-helical segments from Ala2 to Asp7 and Tyr10 to Asn27. Further increases in temperature to 35 degrees C cause the Ala2-Asp7 section to become random coil, while the His13 Phe20 section stays alpha-helical. A mechanism involving unfavorable interactions between charged groups and the alpha-helix macrodipole is proposed for the alpha helix----beta-sheet conversion observed at midrange pH. PMID- 1610810 TI - Sequence-specific assignments of the 1H nuclear magnetic resonance spectra of reduced high-potential ferredoxin (HiPIP) from Chromatium vinosum. AB - The 1H resonances of the high-potential [4Fe-4S]2+ ferredoxin from Chromatium vinosum have been assigned through conventional sequential methodology applied to 2D NMR spectra. Almost 80% of the residues were identified using standard 2D COSY, HOHAHA, and NOESY pulse sequences. These residues correspond to four segments of the primary structure that do not interact strongly with the iron sulfur cluster. A minor correction to the amino acid sequence is strongly suggested by these NMR data. Additional protons more sensitive to the proximity of the cluster were assigned by a combination of NOESY experiments with fast repetition rates and short mixing times and of HOHAHA spectra recorded with reduced spin-lock duration aimed at compensating for the short relaxation rates. Hence, the contributions of 79 residues out of 85 were identified in NMR spectra, among which the assignments of 64 residues were completed. Even the fastest relaxing protons, like those of the cysteine ligands, could be correlated, partly because the strong hyperfine shifts isolate them from the crowded diamagnetic region. However, other protons, in particular those involved in NH-S hydrogen bonds with the iron-sulfur cluster, were more difficult to identify, most probably because their relatively broad signals overlapped with those of protons not or less perturbed by the active site. The availability of the major part of the 1H NMR assignments has enabled the detection and identification of many interresidue NOESY cross peaks. These data are in full agreement with the elements of secondary structure previously revealed by X-ray crystallographic analysis of the protein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610811 TI - Solution structure of endothelin-3 determined using NMR spectroscopy. AB - The aqueous solution structure of the 21-residue vasoactive peptide hormone endothelin-3 has been determined using high-resolution NMR spectroscopy. A total of 177 proton-proton distance measurements and 5 chi 1 dihedral angle constraints derived from NMR spectra were used to calculate the structure using a combination of distance geometry and dynamical simulated annealing calculations. The calculations reveal a highly ordered, compact conformation in which a helical region extending from K9 to C15 lies in close apposition with the C-terminal hexapeptide; this interaction seems to be largely driven by hydrophobic interactions. Structure-activity studies are interpreted in terms of the conformational features of the calculated endothelin-3 structure. PMID- 1610812 TI - Differential helix propensity of small apolar side chains studied by molecular dynamics simulations. AB - A series of oligoalanine molecules with single amino acid replacements in the middle of the chain has been studied by molecular dynamics simulations. Differences in stability of the alpha-helix (as free energies delta delta G degrees) were estimated for the following series of residues: alpha aminoisobutyric acid, alanine, alpha-amino-n-butyric acid, valine, glycine, D alanine, t-leucine (= alpha-amino-beta,beta-dimethyl-n- butyric acid), and proline, arranged here in decreasing order of helix-forming potential. (The results for proline and valine had been reported earlier.) No experimental results were available for alpha-amino-n-butyric acid, D-alanine, and t-leucine at the time these calculations were done. The values of delta delta G degrees, including the three predictions, are in striking agreement with recent experimental results. A combination of free dynamics, dynamics with forced conformational change, and dynamics with forced molecular replacement was used. Conformational distributions were calculated for the peptide backbone of the dipeptides and, where appropriate, for the side chains of the dipeptide and the alpha-helix. The results demonstrate an unexpected level of accuracy for the all atom model used to represent atomic interactions in the simulations. The simulations permit a detailed analysis of different factors responsible for conformational preferences and differences in stability. These conclusions drawn from this analysis agree with accepted qualitative explanations and allow these explanations to be quantitated to an extent not heretofore possible. PMID- 1610813 TI - Membrane-bound conformation of mastoparan-X, a G-protein-activating peptide. AB - Mastoparan-X, a tetradecapeptide from wasp venom, has been proposed to cause secretion from various kinds of cells by the direct activation of GTP-binding regulatory proteins (G proteins) that couple to phospholipase C. The mechanism of the activation has been shown to be very similar to that of G-protein-coupled receptors in vitro, and the interaction with membranes seems to be very important for the activation of G proteins that are membrane-bound [Higashijima, T., Uzu, S., Nakajima, T., & Ross, E. M. (1988) J. Biol. Chem. 263, 6491-6494]. We report here the precise vesicle-bound conformation of mastoparan-X in the presence of perdeuterated phospholipid vesicles, determined by two-dimensional 1H-NMR analyses of transferred nuclear Overhauser effects, combined with distance geometry and molecular dynamics calculations. Of 14 amino acid residues, the C terminal 12 residues take an alpha-helical conformation upon binding to the phospholipid bilayer. The overall structure of the alpha-helix is amphiphilic, with three lysine side chains located on one side and with hydrophobic side chains on the other side. This conformation of mastoparan-X was maintained both in the gel and in the liquid-crystalline phases of the membranes. The conformation described herein will provide a useful basis for understanding conformation-activity relationships of mastoparan analogs as activators of G proteins. These studies will help to design novel potent analogs for the regulation of G proteins and to analyze receptor-G-protein interactions. PMID- 1610814 TI - Characterization of calcium binding to spectrins. AB - Calcium binding to brain and erythrocyte spectrins was studied at physiological ionic strength by a calcium overlay assay and aqueous two-phase partitioning. When the spectrins were immobilized on nylon membranes by slot blotting, the overlay assay showed that even though both spectrins bound 45Ca2+, the brain protein displayed much greater affinity for calcium ions than erythrocyte spectrin did. Since the observed binding was weaker than that displayed by calmodulin under similar conditions, the overlay assay results indicated that the binding must be weaker than 1 microM. The phase partition experiments showed that there are at least two sites for calcium on brain spectrin and that calcium binding to one of these sites is reduced significantly by magnesium ions. From the partition isotherm, the dissociation constants were estimated as 50 microM for the Mg(2+)-independent site and 150 microM for the Mg(2+)-dependent site. The phase partition results also showed that erythrocyte spectrin bound calcium ions at least 1 order of magnitude weaker. By examining calcium binding to slot blotted synthetic peptides, we identified two binding sites in brain spectrin. One mapped to the second putative calcium binding site (EF-hand) in alpha spectrin and the other to the 36 amino acid residue long insert in domain 11. In addition, a tryptic fragment derived from the C-terminal of erythrocyte alpha spectrin, which contained the two postulated EF-hands, also bound calcium. These findings suggest that the calcium signal system may also involve direct binding of calcium to spectrin beside known calcium modulators such as calmodulin and calpain.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610815 TI - Fe2+ and phosphate interactions in bacterial ferritin from Azotobacter vinelandii. AB - Fe2+ binding to both apo- and holo- bacterial ferritin from Azotobacter vinelandii (AVBF) was measured as a function of pH under carefully controlled anaerobic conditions. Fe2+ binding to apo-AVBF is strongly pH dependent with 25 Fe2+ ions/apo-AVBF binding tightly at pH 5.5 and over 150 Fe2+/apo-AVBF at pH 9.0. Holo-AVBF gave a similar pH-dependent binding profile with over 400 Fe2+/AVBF binding at pH of 9.0. Proton release per Fe2+ bound to either AVBF protein increases with increasing pH until a total of about two protons are released at pH 9.0. These binding results are both qualitatively and quantitatively different from corresponding measurements (Jacobs et al., 1989) on apo- and holo- mammalian ferritin (MF) where less Fe2+ binds in both cases. The high level of Fe2+ binding to holo-AVBF relative to that of mammalian ferritin is a consequence of the higher phosphate content in the core of AVBF. Reduction of AVBF by either dithionite or methyl viologen in the absence of chelating agents demonstrated that phosphate, but not Fe2+, is released from the AVBF core in amounts commensurate with the degree of iron reduction, although even at 100% reduction considerable phosphate remains associated with the reduced mineral core. Fe2+ binding to holo-AVBF made deficient in phosphate was lower than that of native AVBF, while the addition of phosphate to native holo-AVBF increased the Fe2+ binding capacity. These results clearly support the role of phosphate as the site of interaction of Fe2+ with the AVBF mineral core.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610816 TI - Sequential nuclear magnetic resonance assignment of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of the pathogenic yeast Candida albicans NIH B-792 strain. AB - The H-1 and H-2 signals of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of Candida albicans NIH B-792 strain by mild acid hydrolysis were assigned by a sequential NMR assignment method that combines two-dimensional 1H-1H correlated spectroscopy (COSY) and two-dimensional nuclear Overhauser enhancement and exchange spectroscopy (NOESY). The results indicated that the H-1 and H-2 of each beta-1,2-linked mannopyranose unit show largely different signals compared with those of the alpha-linked ones and that the correlation between linkages and signals could not be explained by a conventional additivity rule. Furthermore, a regular proportional downfield shift of the H-1 signal was observed in the order of the mannose unit from the reducing terminal except those of the reducing and nonreducing terminal positions. Although the 1H NMR spectra of these oligosaccharides were complicated due to the presence of a large portion of the beta-anomer from the reducing terminal mannose unit, reduction of the oligosaccharides with NaBH4 to the corresponding alcohols gave simple and more readily interpretable 1H NMR spectra. Unexpectedly, however, a shift of H-1 signals by this reduction occurred not only on the second mannose unit but also on the third and fourth mannose units from the modified reducing terminal group of each oligosaccharide alcohol. This result indicates that the reducing terminal mannose unit is able to affect up to the fourth mannose unit from the reducing terminal. The presence of a long-distance interresidue NOE also suggests that the beta-1,2-linked mannooligosaccharides have a compactly folded conformation in solution. PMID- 1610817 TI - Intramolecular catalysis of a proline isomerization reaction in the folding of dihydrofolate reductase. AB - The cis/trans isomerization of the peptide bond preceding proline residues in proteins can limit the rate at which a protein folds to its native conformation. Mutagenic analyses of dihydrofolate reductase (DHFR) from Escherichia coli show that this isomerization reaction can be intramolecularly catalyzed by a side chain from an amino acid which is distant in sequence but adjacent in the native conformation. The guanidinium NH2 nitrogen of Arg 44 forms one hydrogen bond to the imide nitrogen and a second to the carbonyl oxygen of Pro 66 in wild-type DHFR. Replacement of Arg 44 with Leu results in a change of the nature of the two slow steps in refolding from being limited by the acquisition of secondary and/or tertiary structure to being limited by isomerization. The simultaneous replacement of Pro 66 with Ala (i.e., the Leu 44/Ala 66 double mutant) eliminates this isomerization reaction and once again makes protein folding the limiting process. Apparently, one or both of the hydrogen bonds between Arg 44 and Pro 66 accelerate the isomerization of the Gln 65-Pro 66 peptide bond. The replacement of Arg 44 with Leu affects the kinetics of the slow folding reactions in a fashion which indicates that the crucial hydrogen bonds form in the transition states for the rate-limiting steps in folding. PMID- 1610818 TI - Detection of an equilibrium intermediate in the folding of a monomeric insulin analog. AB - To determine the conformational properties of the C-terminal region of the insulin B-chain relative to the helical core of the molecule, we have investigated the fluorescence properties of an insulin analog in which amino acids B28 and B29 have been substituted with a tryptophan and proline residue respectively, ([WB28,PB29]insulin). The biological properties and far-UV circular dichroism (CD) spectrum of the molecule indicate that the conformation is similar to that of native human insulin. Guanidine hydrochloride (GdnHCl)-induced equilibrium denaturation of the analog as monitored by CD intensity at 224 nm indicates a single cooperative transition with a midpoint of 4.9 M GdnHCl. In contrast, when the equilibrium denaturation is observed by steady-state fluorescence emission intensity at 350 nm, two distinct transitions are observed. The first transition accounts for 60% of the observed signal and has a midpoint of 1.5 M GdnHCl. The second transition roughly parallels that observed by CD measurements with an approximate midpoint of 4.5 M GdnHCl. The near-UV CD spectrum, size-exclusion, and ultracentrifugation properties of [WB28,PB29]insulin indicate that this analog does not self-associate in a concentration-dependent manner as does human insulin. Thus, the observed fluorescence changes must be due to specific conformational transitions which occur upon unfolding of the insulin monomer with the product of the first transition representing a stable folding intermediate of this molecule. PMID- 1610819 TI - Similarities in melittin functional group reactivities during self-association and association with lipid bilayers. AB - Competitive labeling of melittin over a range of concentrations in the presence and absence of liposomes provides a series of "snapshots" of the chemical reactivities of melittin's intrinsic nucleophiles. Distinct trends in apparent reactivities were observed for the Gly-1 alpha-amino group and the epsilon-amino groups of Lys-7 and Lys-21 and -23, over a range of concentrations, providing evidence for different forms of associated melittin in solution. The monomer tetramer transition can be followed, in accord with structural details derived from X-ray crystallography. The reactivity behavior of the alpha-amino group of Gly-1 and the epsilon-amino groups of Lys-21 and Lys-23 suggests these groups undergo similar perturbations in their microenvironments during the monomer tetramer transition in free solution. Similar changes in reactivity behavior occur upon association of melittin monomers with bilayer-forming lipids. Together, these findings suggest that the local environments of the N- and C terminal segments have similar physicochemical properties in both the solution tetramer and the lipid-associated complex. The concentration dependence of the chemical properties of melittin is correlated with surface accessibility calculations which are used to provide a framework for interpretation. Aspects of several previously proposed models of membrane lysis can be accounted for by concentration-dependent properties of melittin. PMID- 1610820 TI - Contributions of the polar, uncharged amino acids to the stability of staphylococcal nuclease: evidence for mutational effects on the free energy of the denatured state. AB - In order to quantitate the contributions of the polar, uncharged amino acids to the stability of the native state of staphylococcal nuclease, each of the 13 alanines, 9 glycines, 9 threonines, 6 prolines, 6 glutamines, 6 asparagines, and 3 serines was substituted, either with both alanine and glycine or with 1 of these 2 amino acids plus valine. For each mutant, the stability to reversible denaturation (delta GH2O) was quantitated by determining the Kapp for this reaction as a function of guanidine hydrochloride concentration. In addition, the parameter mGuHCl (= d(delta G)/d[GuHCl]) was calculated from the data. To identify the local structural features responsible for the relatively large and variable changes in delta GH2O and mGuHCl observed for the same type of substitution at different locations in nuclease, statistical correlations were sought between delta GH2O, mGuHCl, and a number of descriptors of the local structure. As with substitutions of the large hydrophobic amino acids [Shortle, D., Stites, W. E., & Meeker, A. K. (1990) Biochemistry 29, 8033-8041], mutation of polar, uncharged residues to Gly leads to a change in stability that, on average, correlates well with the degree to which the wild-type residue is buried. This correlation is especially significant for threonine, an amino acid with both polar and hydrophobic character, but is not demonstrated for the more typically hydrophobic residue alanine. As reported in the previous study of alanine/glycine substitutions of hydrophobic residues, a significant correlation between changes in stability and changes in the value of mGuHCl is again observed, strengthening the conclusion that the putative structural changes in the denatured state which lead to increases or decreases in mGuHCl are responsible for a significant fraction of the stability loss for an average mutant. The existence of this correlation is consistent with the denatured state of wild-type staphylococcal nuclease having evolved to a relatively high free energy via optimization of a balance between a maximal exposure of hydrophobic surface and a minimal gain in chain entropy. On average, mutations are less stable in proportion to the extent of which they perturb this balance. A new and puzzling correlation is reported between the extent of buriedness of a residue in the wild-type native state versus the difference in mGuHCl between the Ala mutation and the Gly mutation at that position. PMID- 1610821 TI - Biphasic effects of alcohols on the phase transition of poly(L-lysine) between alpha-helix and beta-sheet conformations. AB - Poly(L-lysine) exists as a random-coil at neutral pH, an alpha-helix at alkaline pH, and a beta-sheet when the alpha-helix poly(L-lysine) is heated. The present Fourier-transform infrared (FTIR) study showed that short-chain alcohols (methanol, ethanol, and 2-propanol) partially transformed alpha-helix poly(L lysine) to beta-sheet when their concentrations were low. At higher concentrations, however, these alcohols reversed the reaction, and the alcohol induced beta-sheet was transformed back to alpha-helix structure. The reversal occurred at 1.40 M methanol, 0.96 M ethanol, and 0.55 M 2-propanol. The alcohol effects on the secondary structure were further investigated by circular dichroism (CD) on the thermally induced beta-sheet poly(L-lysine). Methanol, ethanol, and 1-propanol, but not 1-butanol, shifted the negative mean-residue ellipticity at 217 nm of the beta-sheet poly(L-lysine) to the positive side at low concentrations of the alcohols and to the negative side at high concentrations. With 1-butanol, only the positive-side shift was observed. The positive-side shift at low concentrations of alcohols indicates enhancement of the hydrophobic interactions among the side chains of the polypeptide in the beta sheet conformation. The negative-side shift indicates a partial transformation to alpha-helix. The shift from the positive to negative side occurred at 7.1 M methanol, 4.6 M ethanol, and 3.1 M 1-propanol. The alcohol concentrations for the beta-to-alpha transition were higher in the CD study than in the IR study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610822 TI - Cement precursor proteins of the reef-building polychaete Phragmatopoma californica (Fewkes). AB - Two distinctive 3,4-dihydroxyphenyl-L-alanine-(DOPA-) containing proteins (Pc-1 and Pc-2) have been isolated and partially characterized from the thorax of the reef-building sabellariid Phragmatopoma californica. They are the first such reported from the phylum Annelida. The proteins are presumed to be soluble precursors of the quinone-tanned cement used to bind particulate materials in the construction of the tubes that serve as habitats for the worms. The proteins have apparent molecular weights ranging from 18,000 to 20,000 and isoelectric point greater than or equal to 8.0. Both proteins consist of repeated sequence motifs in their primary structure. Pc-1 has repeats of (XGGY*GY*GAK) where X = V, L, I, AA, or KV, and Y* is DOPA or tyrosine. Pc-2, in contrast, appears to have repeats of (X1-[GGY*]n-[GA]m-X2-[HP(A)V]p-HK) where X1 can be AL, A, or F; X2 can be WG or absent; n and m can be 1 or 2, and p = 0-2. Both protein families appear to share the same C-terminal sequence ALGGY*GAGA. Of the DOPA-containing proteins characterized from other phyla, Phragmatopoma cement precursors most resemble those from the liver fluke Fasciola hepatica and the mussel Trichomya hirsuta. PMID- 1610823 TI - Synthetic model proteins: the relative contribution of leucine residues at the nonequivalent positions of the 3-4 hydrophobic repeat to the stability of the two stranded alpha-helical coiled-coil. AB - Our de novo designed coiled-coil model protein consists of two identical 35 residue polypeptide chains arranged in a parallel and in-register alignment via interchain hydrophobic interactions and a disulfide bridge at the position 2 between two helices. To quantitate the relative contribution of leucine residues at the nonequivalent position of the 3-4 hydrophobic repeat to the stability of the two-stranded alpha-helical coiled-coil, a single alanine was systematically substituted for a leucine in each chain at position "a" (9, 16, 23, or 30) or "d" (5, 12, 19, 26, or 33). The formation and stability of the coiled-coils were determined by circular dichroism studies in the absence and presence of guanidine hydrochloride. All the proteins with an alanine substituted at position a have a similar stability ([Gdn.HCl]1/2 ranges from 2.6 to 2.9 M), while all the proteins with an alanine substituted at position d have similar stability ([Gdn.HCl]1/2 ranges from 3.6 to 4.2 M), except for the proteins with an alanine substituted in the C-terminal heptad. The greater decrease in stability observed for a Leu--- Ala mutation at position a (the average delta delta Gu value is 3.3 kcal/mol) compared to those where the substitution was effected at position d (the average delta delta Gu value is 2.0 kcal/mol) indicates that an Ala mutation at position a has a greater effect on the side-chain packing and hydrophobic interactions in the coiled-coil than an Ala mutation at position d.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610824 TI - Binding of adenine nucleotides to the F1-inhibitor protein complex of bovine heart submitochondrial particles. AB - The binding of ATP radiolabeled in the adenine ring or in the gamma- or alpha phosphate to F1-ATPase in complex with the endogenous inhibitor protein was measured in bovine heart submitochondrial particles by filtration in Sephadex centrifuge columns or by Millipore filtration techniques. These particles had 0.44 +/- 0.05 nmol of F1 mg-1 as determined by the method of Ferguson et al. [(1976) Biochem. J. 153, 347]. By incubation of the particles with 50 microM ATP, and low magnesium concentrations (less than 0.1 microM MgATP), it was possible to observe that 3.5 mol of [gamma-32P]ATP was tightly bound per mole of F1 before the completion of one catalytic cycle. With [gamma-32P]ITP, only one tight binding site was detected. Half-maximal binding of adenine nucleotides took place with about 10 microM. All the bound radioactive nucleotides were released from the enzyme after a chase with cold ATP or ADP; 1.5 sites exchanged with a rate constant of 2.8 s-1 and 2 with a rate constant of 0.45 s-1. Only one of the tightly bound adenine nucleotides was released by 1 mM ITP; the rate constant was 3.2 s-1. It was also observed that two of the bound [gamma-32P]ATP were slowly hydrolyzed after removal of medium ATP; when the same experiment was repeated with [alpha-32P]ATP, all the label remained bound to F1, suggesting that ADP remained bound after completion of ATP hydrolysis. Particles in which the natural ATPase inhibitor protein had been released bound tightly only one adenine nucleotide per enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610825 TI - Time-resolved infrared spectroscopy of electron transfer in bacterial photosynthetic reaction centers: dynamics of binding and interaction upon QA and QB reduction. AB - Light-induced forward electron transfer in the bacterial photosynthetic reaction center from Rhodobacter sphaeroides was investigated by time-resolved infrared spectroscopy. Using a highly sensitive kinetic photometer based on a tunable IR diode laser source [Mantele, W., Hienerwadel, R., Lenz, F., Riedel, W. J., Grisar, R., & Tacke, M. (1990a) Spectrosc. Int. 2, 29-35], molecular processes concomitant with electron-transfer reactions were studied in the microsecond-to second time scale. Infrared (IR) signals in the 1780-1430-cm-1 spectral region, appearing within the instrument time resolution of about 0.5 microseconds, could be assigned to molecular changes of the primary electron donor upon formation of a radical cation and to modes of the primary quinone electron acceptor QA and its environment upon formation of QA-. These IR signals are consistent with steady state FTIR difference spectra of the P+Q- formation [Mantele, W., Nabedryk, E., Tavitian, B. A., Kreutz, W., & Breton, J. (1985) FEBS Lett. 187, 227-232; Mantele, W., Wollenweber, A., Nabedryk, E., & Breton, J. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 8468-8472; Nabedryk, E., Bagley, K. A., Thibodeau, D. L., Bauscher, M., Mantele, W., & Breton, J. (1990) FEBS Lett. 266, 59-62] and with time-resolved FTIR studies [Thibodeau, D. L., Nabedryk, E., Hienerwadel, R., Lenz, F., Mantele, W., & Breton, J. (1990) Biochim. Biophys. Acta 1020, 253-259]. At given wavenumbers, kinetic components with a half-time of approximately 120 microseconds were observed and attributed to QA----QB electron transfer. The time resolved IR signals, in contrast to steady-state experiments where full protein relaxation after electron transfer can occur, allow us to follow directly the modes of QA and QB and their protein environment under conditions of forward electron transfer. Apart from signals attributed to the primary electron donor, signals are proposed to arise not only from the C = O and C = C vibrational modes of the neutral quinones and from the C-O and C-C vibrations of their semiquinone anion form but also from amino acid groups forming their binding sites. Some of the signals appearing with the instrument rise time as well as the transient 120 microseconds signals are interpreted in terms of binding and interaction of the primary and secondary quinone electron acceptor in the Rb. sphaeroides reaction center and of the conformational changes in their binding site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1610826 TI - Biochemical characterization of the Oct-2 POU domain with implications for bipartite DNA recognition. AB - B-cell specific regulation of immunoglobulin gene expression provides a model for the interaction of promoter and enhancer elements with eukaryotic sequence specific DNA binding proteins. A critical element of this system, the octamer site (5'-ATGCAAAT-3'), is recognized by the B-cell transcription factor Oct-2. Octamer recognition is mediated by the POU domain, a conserved structural motif which--like the zinc finger and leucine zipper--defines a family of related transcription factors. Homologies among POU sequences suggest a bipartite structure, consisting of an N-terminal POU-specific subdomain and C-terminal variant homeodomain connected by a linker of variable length and sequence. As a first step toward a molecular understanding of the Oct-2 POU domain and its mechanism of DNA recognition, we have overexpressed in Escherichia coli the intact POU domain and subdomains as thrombin-cleavable fusion proteins and have purified these fragments to homogeneity following digestion with thrombin. Biochemical and biophysical characterization yields the following results. (i) The intact POU domain (166 residues) is monomeric and exhibits high-affinity octamer-specific DNA-binding activity. (ii) Limited proteolytic digestion demonstrates that the POU domain contains two proteolytically stable subdomains (the POU-specific subdomain and the variant homeodomain) connected by a proteolytically sensitive linker. (iii) The isolated subdomains are each monomeric and do not interact to form noncovalent heterodimers.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610827 TI - Regulation of cytoplasmic tubulin carboxypeptidase activity during neural and muscle differentiation: characterization using a microtubule-based assay. AB - A cycle of posttranslational modification of alpha-tubulin has previously been described in higher eukaryotes, in which a C-terminal tyrosine residue is removed and replaced by two complementary cytoplasmic enzymes. The activity of the detyrosinating enzyme, tubulin carboxypeptidase (TCP), and its potential for regulating the level of detyrosinated (Glu) subunits in microtubules (MTs) is of great interest, since TCP catalyzes the primary modification of tubulin and since the level of Glu alpha-tubulin in MTs increases during a variety of differentiative and morphogenetic events. As a first step in examining the role of TCP in cellular morphogenesis, it was necessary to develop an assay for TCP with sufficient sensitivity and specificity to detect TCP activity during these events. Unlike previously described assays for TCP, ours makes use of the affinity TCP exhibits for MTs. NGF-induced neurite outgrowth in PC-12 cells was accompanied by a moderate (approximately 2-fold) increase in TCP activity, while myogenesis of L6 cells resulted in an almost insignificant decrease in activity. Measurements of TCP activity during differentiation were correlated with the level of extract Tyr tubulin, which increased (approximately 37%) during neurite outgrowth and was unchanged during myogenic differentiation. Our results suggest that TCP activity is regulated relative to its substrate, Tyr tubulin, and that changes in MT dynamics, rather than enzymatic activities, are the primary determinants of MT posttranslational modification state during differentiation. In addition, the assay we have devised for TCP and the characterization of TCP during differentiation may allow the future delineation of the mechanism(s) of regulation of TCP and the role this enzyme plays in modulating MT function during differentiation. PMID- 1610828 TI - Cutoff size does strongly influence molecular dynamics results on solvated polypeptides. AB - The behavior of a 17-residue model peptide is analyzed by means of molecular dynamics simulations including explicitly more than a thousand water molecules. On the basis of the charge-group concept, Coulomb interactions are truncated for three values of the cutoff radius: 0.6, 1.0, and 1.4 nm. It is found that the stability of an alpha-helix, which acts as a common starting configuration, is a function of the cutoff size. While the overall stability of the helix is conserved in a simulation using a cutoff of 1.0 nm, it is lost within a very short period of 100 ps when the cutoff is increased to 1.4 nm. This demonstrates that the commonly used cutoff size of 1.0 nm is inappropriate because it does not ensure the convergence of Coulomb interactions. In order to permit an independent judgment, we have performed a 225-ps simulation using the Ewald summation technique, which is more elaborate but circumvents the problem to find an appropriate cutoff value. In contrast to the 1.4-nm cutoff trajectory, the Ewald technique simulation conserves the helical character of the peptide conformation. This demonstrates that even 1.4 nm is too short a cutoff. Due to the fundamental uncertainty introduced by the use of a simple cutoff, this truncation scheme seems questionable for molecular dynamics simulations of solvated biomolecules. PMID- 1610829 TI - Mechanism of action of sparsomycin in protein synthesis. AB - Before CI isomerizes to C*I, we detect a competitive phase of inhibition (Ki = k5/k4 = 0.05 microM) which eventually, by increasing the concentration of I, becomes linear mixed noncompetitive and involves C*I in place of CI. The equilibration of C and I according to reaction 2 is much slower than the equilibration between C and S in reaction 1 (time-dependent inhibition). The inactivation plots obey reaction 2 and allow us to estimate k6 as equal to 2.2 min-1. The isomerized C*I, free of excess I, can be studied as a mixture with complex C. From the kinetics of the regeneration of C from C*I, in the presence of puromycin, we can estimate k7 to be between 0.22 min-1 and 0.06 min-1. Although the isomerized C*I survives after adsorption on cellulose nitrate filter disks, it does not survive after gel chromatography on a Sepharose CL-4B column but is converted quantitatively to complex C containing D of unchanged reactivity. This result does not support the proposed [Flynn, G. A., & Ash, R. J., (1990) Biochem. Biophys. Res. Commun. 166, 673-680] chemical reaction between D and I toward new products. The isomerized C*I can be obtained not only from the already-made complex C but also de novo from D, R, and M. In the latter case, the reactions which lead to C are represented by the following hypothetical scheme: D + R + M in equilibrium with DRM or C (binding reaction). When C*I is formed de novo, this reaction is coupled to reaction 2 and the ultimate product is a mixture of C and C*I.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610830 TI - Mechanism of inhibition of the class C beta-lactamase of Enterobacter cloacae P99 by phosphonate monoesters. AB - The class C serine beta-lactamase of Enterobacter cloacae P99 was inhibited by a series of aryl methylphosphonate monoester monoanions. The effectiveness of these inhibitors was promoted by an acylamido substituent on the methyl group and a good leaving group at phosphorus. The former preference suggests that noncovalent interaction of these inhibitors with the enzyme resembles that of substrates, while the latter suggests that nucleophilic displacement at phosphorus occurs as part of the inhibition mechanism. The truth of the latter proposition was confirmed by observation of release of 1 equiv of phenol concomitant with inhibition and of the presence of an equivalent amount of 14C-label on the enzyme after inhibition by a 14C-labeled phosphonate. The hydrolytically inert nature of the enzyme-inhibitor adduct, and its 31P chemical shift, suggested that O phosphonylation of the enzyme had occurred. Although, by analogy with substrates, one might expect that the hydroxyl of the active site serine residue would be covalently modified by these inhibitors, successive alkali and acid treatment of the enzyme-inhibitor adduct generated no pyruvate. Instead, 1 equiv of lysinoalanine was found. This product was rationalized to arise through intramolecular capture by an adjacent lysine amine group of the dehydroalanine residue produced by alkali treatment of an O-phosphonylated serine residue. One equivalent of lysinoalanine was also produced by alkali treatment of the enzyme that had been inhibited by 6 beta-bromopenicillanic acid, a mechanism-based inhibitor known to acylate the hydroxyl group of the active site serine residue. It is therefore likely that the aryl phosphonates phosphonylate this residue. These compounds should be useful as beta-lactamase active site titrants and as sources of fresh insight into the chemical properties of the active site. The significant mechanistic features of the inhibition, in particular its strong leaving group dependence and the distinctive ability of the beta-lactamase active site to stabilize a dianionic transition state containing a pentacoordinated phosphorus, are discussed with respect to the active site structure. The comparison with phosph(or/on)yl inhibitors of serine proteinases is made, and the mechanism-based features of inhibition of serine hydrolases by phosph(on)ates are noted. PMID- 1610831 TI - Role of Asp222 in the catalytic mechanism of Escherichia coli aspartate aminotransferase: the amino acid residue which enhances the function of the enzyme-bound coenzyme pyridoxal 5'-phosphate. AB - Asp222 is an invariant residue in all known sequences of aspartate aminotransferases from a variety of sources and is located within a distance of strong ionic interaction with N(1) of the coenzyme, pyridoxal 5'-phosphate (PLP), or pyridoxamine 5'-phosphate (PMP). This residue of Escherichia coli aspartate aminotransferase was replaced by Ala, Asn, or Glu by site-directed mutagenesis. The PLP form of the mutant enzyme D222E showed pH-dependent spectral changes with a pKa value of 6.44 for the protonation of the internal aldimine bond, slightly lower than that (6.7) for the wild-type enzyme. In contrast, the internal aldimine bond in the D222A or D222N enzyme did not titrate over the pH range 5.3 9.5, and a 430-nm band attributed to the protonated aldimine persisted even at high pH. The binding affinity of the D222A and D222N enzymes for PMP decreased by 3 orders of magnitude as compared to that of the wild-type enzyme. Pre-steady state half-transamination reactions of all the mutant enzymes with substrates exhibited anomalous progress curves comprising multiphasic exponential processes, which were accounted for by postulating several kinetically different enzyme species for both the PLP and PMP forms of each mutant enzyme. While the replacement of Asp222 by Glu yielded fairly active enzyme species, the replacement by Ala and Asn resulted in 8600- and 20,000-fold decreases, respectively, in the catalytic efficiency (kmax/Kd value for the most active species of each mutant enzyme) in the reactions of the PLP form with aspartate. In contrast, the catalytic efficiency of the PMP form of the D222A or D222N enzyme with 2-oxoglutarate was still retained at a level as high as 2-10% of that of the wild-type enzyme. The presteady-state reactions of these two mutant enzymes with [2-2H]aspartate revealed a deuterium isotope effect (kH/kD = 6.0) greater than that [kH/kD = 2.2; Kuramitsu, S., Hiromi, K., Hayashi, H., Morino, Y., & Kagamiyama, H. (1990) Biochemistry 29, 5469-5476] for the wild-type enzyme. These findings indicate that the presence of a negatively charged residue at position 222 is particularly critical for the withdrawal of the alpha-proton of the amino acid substrate and accelerates this rate-determining step by about 5 kcal.mol-1. Thus it is concluded that Asp222 serves as a protein ligand tethering the coenzyme in a productive mode within the active site and stabilizes the protonated N(1) of the coenzyme to strengthen the electron-withdrawing capacity of the coenzyme. PMID- 1610832 TI - Role of phosphorylated aminoacyl residues in generating atypical consensus sequences which are recognized by casein kinase-2 but not by casein kinase-1. AB - Casein kinase-2 (CK-2) is a ubiquitous Ser/Thr specific protein kinase that recognizes phosphorylatable residues located upstream of acidic determinants, its consensus sequence being Ser(Thr)-Xaa-Xaa-Acidic. Here we show that the phosphotetrapeptide AcSer(P)-Ser(P)-Ser-Ser(P), which is devoid of the canonical consensus sequence, is nevertheless phosphorylated by CK-2 with rates comparable to that of typical peptide substrates Ser-Glu-Glu-Glu-Glu-Glu and Arg-Arg-Arg-Glu Glu-Glu-Thr-Glu-Glu-Glu routinely employed for assaying CK-2 activity. The phosphopeptide AcSer(P)-Ser-Ser(P) [but not Ac-Ser-Ser(P)-Ser(P) or AcSer(P) Ser(P)-Ser] is also phosphorylated albeit less efficiently than AcSer(P)-Ser(P) Ser-Ser(P). Further N-terminal elongation with additional phosphoseryl residues to give the peptides AcSer(P)-Ser(P)-Ser(P)-Ser-Ser(P) and AcSer(P)-Ser(P)-Ser(P) Ser(P)-Ser-Ser(P) does not improve but rather slightly decreases the phosphorylation efficiency by CK-2. These two peptides are conversely excellent substrates for CK-1, which does not appreciably phosphorylate either AcSer(P)-Ser Ser(P) or AcSer-(P)-Ser(P)-Ser-Ser(P). Either individual or multiple replacement of the phosphorylated residues with glutamic acid in the peptide AcSer(P)-Ser(P) Ser-Ser(P) drastically reduces the phosphorylation efficiency by CK-2, the phosphoseryl residue at position -2 playing an especially crucial role which cannot be surrogated by glutamyl residues.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610833 TI - The 23-kilodalton protein, a substrate of protein kinase C, in bovine neutrophil cytosol is a member of the S100 family. AB - A bovine neutrophil protein termed p23 because of an apparent molecular mass of 23 kDa in SDS-PAGE is present in large amounts both in a soluble form in the cytosolic fraction of bovine neutrophil homogenates and associated to the cytoskeleton. P23 is accompanied during the first steps of the purification procedure by a smaller size protein termed p7 on the basis of a rate of migration in SDS-PAGE corresponding to a 7-kDa protein [Stasia, M. J., Dianoux, A. C., & Vignais, P. V. (1989) Biochemistry 28, 9659-9667]. The two proteins, p23 and p7, have been purified to homogeneity by an improved procedure consisting of two chromatographic steps. The electrospray mass spectrometry technique applied to p23 and p7 indicated molecular masses close to 17 and 10 kDa, respectively, significantly different from the masses derived by SDS-PAGE. Bovine neutrophil p23 and p7 presented large primary structure homologies with two human proteins, MRP14 and MRP8, which are expressed in large amounts in macrophages under conditions of chronic inflammation. In addition, p23 and p7 cross-reacted with monoclonal antibodies specific of MRP14 and MRP8. Bovine p23 and p7 bound Ca2+, and their amino acid sequences contained two Ca(2+)-binding domains per protein, largely identical to those of human MRP14 and MRP8. Bovine p23 and p7 associated together to form a heterodimeric complex, which largely escaped attack by trypsin, whereas the isolated p23 and p7 components were readily digested. These features are typical of Ca(2+)-binding proteins belonging to the S100 family.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610834 TI - Spontaneous and protein-mediated intermembrane transfer of the antiretroviral liponucleotide 3'-deoxythymidine diphosphate diglyceride. AB - Phospholipid conjugates of antiretroviral nucleosides show activity against the human immunodeficiency virus in vitro [Hostetler, K. Y., Stuhmiller, L. M., Lenting, H. B. M., Van den Bosch, H., & Richman, D. D. (1990) J. Biol. Chem. 265, 6112-6117]. In order to gain insight into the membrane association and the spontaneous and protein-mediated intermembrane transfer of these compounds, we have synthesized the fluorescent analog 3'-deoxythymidine diphosphate 1-myristoyl 2-(10-pyren-1-yl-decanoyl)glycerol. The compound readily incorporated into ethanol-injection vesicles, but the stability of the fluorescent probe (10% of total lipid) in the lipid bilayer was less than that of 1-myristoyl-2-(10-pyren-1 yldecanoyl)phosphatidylcholine. Using a donor-acceptor vesicle assay system, half times for spontaneous transfer at 25 and 37 degrees C were 20 and 100 min, respectively. The liponucleotide was rapidly transferred between membranes by the nonspecific lipid-transfer protein at a rate at least 10-fold that of the corresponding phosphatidylcholine. Depletion of the liponucleotide from the outer monolayer of vesicles by a large excess of nonspecific lipid-transfer protein indicated a transbilayer distribution similar to the mass distribution of phospholipids. Essentially no flip-flop of the inner monolayer liponucleotide was observed. PMID- 1610835 TI - Interactions between the trp repressor and its operator sequence as studied by base analogue substitution. AB - A series of modified trp operator sequences has been prepared by the incorporation of seven different base analogues. Four of the analogues allow the site-specific deletion of functional groups present on the dA-dT and dT-dA base pairs at positions -4/+4 and -5/+5 in the trp operator. The remaining three analogues permit the incorporation of structural analogues of the native dA-dT or dG-dC base pairs. The duplex operator sequences all exhibit Tm values well above ambient temperature (48-70 degrees C), and these values generally correlate very well with the number of interstrand hydrogen bonds present. The affinity between the trp repressor and 14 modified operator sequences was examined using a recently developed alkaline phosphatase protection assay. The results from the analogue sequences used in this study suggest that the structure of the dA-dT or dT-dA base pairs at positions -4/+4 and -5/+5, respectively, has relatively little effect upon the solution binding by the trp repressor, but the protein is very sensitive to the orientation of the amino and carbonyl functional groups at the -4/+4 positions, which are involved in the formation of an interbase hydrogen bond present in the major groove. (The term structure in this case refers to the hydrogen bonding structure of the base pairs. We recognize that the introduction of conservative functional group deletions or reversals may affect other structural criteria such as hydration.) The deletion of individual functional groups from the operator sequence suggests that the carbonyl at dT+4 is critical for formation of the high-affinity sequence-specific complex. Additionally, the thymine methyl group at dT+4 and the N7 nitrogen of dA+5 appear to be critical contacts necessary for high-affinity binding by the repressor. The thymine carbonyl and the adenine N7 nitrogen are each responsible for approximately -1.5 kcal/mol of apparent free energy of binding. The thymine methyl provides a somewhat smaller contribution of -0.7 kcal/mol. Deletion of either of the adenine amino groups at dA-4 or dA+5 results in a sequence that binds to the repressor with a higher affinity than observed with the native sequence; this can be explained in that the functional groups lost are not critical for binding, and the resulting increased flexibility of the operator, or the creation of a more hydrophobic surface at these sites, enhances van der Waals contacts between the protein and the nucleic acid. PMID- 1610836 TI - The mRNA binding track in the Escherichia coli ribosome for mRNAs of different sequences. AB - Interactions between mRNA and rRNA on the 30S ribosomal subunit or 70S ribosome have been determined by photochemical cross-linking experiments using synthetic mRNA analogs substituted with 4-thiouridine. A set of RNA molecules containing different sequences has been used to determine the extent to which binding contacts are sequence dependent. The 16S rRNA and 23S rRNA nucleotides that form a part of the binding site have been identified by reverse transcription. The nucleotides are U1381, G1338, G1300, G1156, A845, U723, G693, A532, G497, U420, G413/A412, and G436 of 16S rRNA and U887 of 23S rRNA. Several additional nucleotides (U1065 of 23S rRNA and A1227, G818, G524, and G423 of 16S rRNA) are seen for some, but not all, of the mRNAs. Results obtained with two mRNAs containing the Shine-Dalgarno sequence were similar to those obtained with mRNAs lacking the Shine-Dalgarno sequence. Eight of these cross-linking sites were also seen when a mixture of RNA was used in which there are 12 random nucleotides preceding and seven random nucleotides succeeding an AUG codon. These results indicate that to a large extent placement of the mRNA in the ribosome does not depend upon its primary sequence. PMID- 1610837 TI - Effect of phospholipid unsaturation on protein kinase C activation. AB - To examine the hypothesis that physical features of the membrane contribute to protein kinase C activation, phosphatidylcholine/phosphatidylserine/diolein (70:25:5) vesicles of defined acyl chain composition were tested for their ability to activate the enzyme. Maximal activation was found to correlate with the mole percent unsaturation in the system. Unsaturation could be provided by either the phosphatidylserine or the phosphatidylcholine component. Vesicles containing 5 mol% diolein but lacking any unsaturation in the phospholipid did not support activity, indicating that acidic head groups alone are not sufficient for activity. The saturated lipid vesicles could be rendered effective but only at very high (25 mol%) concentrations of diolein. The degree of acyl chain unsaturation and the positioning of the double bond had little effect on the activity, suggesting that the effect of the unsaturation is due to some physical property of the lipid rather than to a specific lipid-protein interaction. Addition of cholesterol to both saturated and unsaturated systems indicated that fluidity, as assessed by fluorescence anisotropy, did not correlate with activity. These results suggest that a physical property of the membrane other than fluidity is important for the activation of protein kinase C. A model for protein kinase C activation involving phase separation and/or head group spacing is discussed. PMID- 1610838 TI - Involving parents in their adolescents' health: a role for school clinics. PMID- 1610839 TI - Composition of milk in adolescents. PMID- 1610840 TI - The children of Kauai: resiliency and recovery in adolescence and adulthood. PMID- 1610841 TI - Bringing parents into school clinics: parent attitudes toward school clinics and contraception. AB - Prior to implementing a change in school clinic policy to allow dispensing of contraceptives, parents of school-based clinic (SBC) enrollees were surveyed regarding attitudes toward clinic quality of care, desired services, and contraceptive distribution. Telephone interviews were conducted with a systematic sample of 262 parents who normally are in charge of the adolescent's health care. Parental opinion was felt to be crucial in shaping Baltimore SBC contraception policy. Parents overwhelmingly endorsed current clinic services including family planning for sexually active teens, annual physicals, and drug and alcohol counseling. Most parents rated the SBC as excellent (25%) or very good (36%), although a substantial minority found it difficult to rate the clinics (27%, "don't know"). Parents with prior verbal contact (45%) were more likely to rate the clinic as excellent (35% versus 16%) and less likely to respond "don't know" (13% versus 38%, p less than 0.001). Parent attitudes toward contraception was context specific: 63% endorsed and 27-30% opposed prescribing and dispensing. If a boy (or girl) was already having sex, 76% (or 75%) of parents supported and 14% (or 17%) opposed providing birth control pills or condoms. With parental permission, 93% supported contraception and only 3% were opposed. No differences were found by age, race, gender, or grade of student. Prior verbal communication with the clinic did not affect parent attitudes toward contraception. Consideration of parent attitudes was critical to changing SBC contraceptive dispensing policy in Baltimore. Contraceptive distribution, after counseling and necessary medical care, was initiated in September 1990. The parent and community response has been very supportive. PMID- 1610842 TI - A comparison of inner-city and upper-middle class youths' exposure to violence. AB - Exposure to violence in healthy adolescents has not been explored. We questioned 838 youths (ages 11-24 years; 620 females) from two medical clinics. The Exposure to Violence Questionnaire was completed by 403 inner-city adolescents (inner-city group), and 435 middle-to-upper class youths (resort group). Inner-city participants were more often victims, knew of victims, and witnessed more assaults, rapes, knifings, life-threatening events, and murders than their resort group counterparts. In both groups, males were more likely to have been victims, witnesses, and to have known victims personally than were females, except for sexually related crimes. In both settings, youths often did not seek medical or psychological help after victimization. Adolescents are exposed to a startling amount of violence. Violence prevention should be targeted to the inner-city male population. PMID- 1610843 TI - Substance use in a school-based clinic population: use of the randomized response technique to estimate prevalence. AB - Students attending school-based clinics acknowledge only minimal involvement with drug or alcohol use. In order to explain this unanticipated finding, we used a statistical method called randomized response to study adolescents in one school based clinic. The sample consisted of 133 students (57% female; 75% black, 20% Hispanic, 5% other; and 58% grades 9-10, 42% grades 11-12). Using both lifetime and 30-day prevalence rates, these students revealed more cigarette smoking and alcohol use on randomized response than they had on questionnaires completed earlier the same academic year, minimal involvement with either marijuana or cocaine use by either method, and a similar amount of sexual activity by both methods. This study demonstrates that randomized response can be a useful method to generate more truthful group responses from adolescents. PMID- 1610844 TI - Adolescent suicide attempters: do physicians recognize them? AB - The single most important risk factor for adolescent suicide is a previous attempt. It is unclear if physicians can identify adolescents who have attempted suicide. Our objectives were to determine the prevalence of previous attempts in an adolescent clinic population, if physicians identify attempters, and if attempters demonstrate persistent distress. Of 332 patients aged 12-19 years attending a medical clinic, 48 (14.5%) reported a previous attempt. The physician's visit note documented that only 8 (16.7%) of the 48 attempters were asked about suicidal behavior. Attempters were more likely than nonattempters (p less than 0.05) to be female; to come to clinic without a guardian; to give a chief complaint pertaining to sexually transmitted disease, obstetrics gynecology, or mental health; and to report previous mental health care. Attempters had poorer mean scores (p less than 0.05) on validated subscales for family relationships, social competence, depression, unpopularity, somatic complaints, thought disorders, delinquency, aggression, and identity. We conclude that suicide attempts are common among adolescent clinic patients, that physicians may not recognize attempters, and that attempters remain distressed and in need of care. Physicians who see adolescents for routine medical problems must consider the potential for self-destructive behavior, regardless of the presenting complaint. PMID- 1610846 TI - Tangible differences between adolescent-oriented and adult-oriented prenatal care. AB - Comprehensive prenatal care reduces many of the risks associated with adolescent childbearing. To learn why this intervention strategy is successful, we compared the care received by 123 poor, black, younger than 19-year-olds in an adolescent oriented prenatal program to that received by 72 sociodemographically similar, black, 19-30-year-olds in a university hospital-based prenatal clinic. We found that adolescents entered care later (13.6 +/- 5.6 vs. 11.7 +/- 3.4 weeks; p less than 0.01) and were less likely to obtain an adequate quantity of care then were adults (45.5% vs. 61.1%; p = 0.04). However, teens were enrolled in the Women, Infant, and Children (WIC) food supplement program more rapidly than adults (within 7 +/- 6 vs. 10 +/- 6 weeks of the first prenatal visit; p = 0.002), were referred more often to community service agencies for help with nonobstetric, psychosocial, and financial problems (37.4% vs. 18.3%; p less than 0.0001), and were tested and treated more frequently for sexually transmitted diseases (p less than 0.0001). When the adolescents entered care they were smaller, had lower hematocrits, more social and behavioral problems, poorer diets, and more sexually transmitted diseases than did the adults. Later in gestation, however, hematocrits, diets, weight gain, and birth outcomes were similar in the two groups. The implications of these findings for health care providers and for further research are discussed. PMID- 1610847 TI - Syphilis screening in adolescents. AB - Routine screening for syphilis among sexually active adolescents is recommended by the American Academy of Pediatrics, but there are few data about clinical application of these recommendations. We examined the yield of a syphilis screening program in one ambulatory adolescent medicine clinic. A rapid plasma reagin (RPR) has been recommended for all sexually active adolescents. Of 630 patients screened for syphilis by RPR, ten patients had reactive syphilis serologies and 4 had active syphilis. Of these, 2 patients had signs or symptoms consistent with primary or secondary syphilis, and 2 patients with active syphilis had clinical evidence of another sexually transmitted disease but no clinical manifestations of syphilis. Of the 10 reactive serologies, 6 represented previously treated cases or a false positive. We conclude that screening should be done for those at high risk for syphilis or those adolescents with sexually transmitted diseases. PMID- 1610849 TI - Bibliography of recent journal articles (July to December 1991). PMID- 1610848 TI - Osteoporosis as the presenting sign of leukemic relapse in an adolescent: case report and literature review. AB - Osteoporosis in adolescence is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Osteoporotic vertebral collapse is an uncommon presenting sign of acute lymphoblastic leukemia (ALL). We describe a 13-year-old boy with osteoporotic vertebral collapse secondary to relapse of ALL whose blood count and blood morphology were normal but whose 1,25 = (OH2) = vitamin D level was deficient. A combination of chemotherapy, calcitriol and calcitonin therapy was successful in reversing the process. His case is presented to describe the diagnostic and therapeutic issues involved. PMID- 1610845 TI - Early adolescent knowledge and attitudes about circumcision: methods and implications for research. AB - The psychosocial effects of circumcision status on the adolescent male are unclear. This study explored methods for assessing attitudes toward circumcision of early adolescents and differences in satisfaction between circumcised and uncircumcised males that would warrant further investigation. Seventy-three boys, aged 11 through 14 years completed the Petersen Body Image Scale and a questionnaire concerning their own circumcision status, satisfaction with that status, and perceptions about the status of other family members and peers. To assess knowledge, subjects identified diagrams depicting differing circumcision states during a personal interview. Physical examination confirmed reported circumcision status. Of the study group, 19% (n = 14) were uncircumcised. Use of visual aids to report circumcision status was more accurate (92%) than self report (68%). Circumcised boys scored higher on satisfaction items than did uncircumcised boys, (t(15.65) = -3.96, p less than 0.001). No differences in general body image were found between groups. Further research that examines psychosocial outcomes of circumcision status is necessary. PMID- 1610850 TI - Safety of oral contraceptives for teenagers. American College of Obstetricians and Gynecologists. AB - By age 18, 51% of adolescent women will be sexually active. Oral contraceptives are a safe method to avoid the potentially disastrous outcome of an unwanted pregnancy. The overall risks of taking oral contraceptives are much less than the risks of pregnancy (20). Specifically, the risks associated with the use of oral contraceptives by teenagers are negligible. Low-dose oral contraceptives have not been linked with either heart attack or stroke in contemporary U.S. studies. While the risk of thromboembolism in oral contraceptive users as a whole may be increased over that of the general population, the risk to teenagers, especially those who do not smoke, is minimal. The risk of death from oral contraceptive use for teenagers is virtually nil (12). As with all medical choices, the benefits of a treatment must be weighed against any potential risks. For adolescents, the benefits associated with the use of oral contraceptives outweigh the risks, particularly those of pregnancy. However, teenagers at risk for sexually transmitted diseases should be advised to use a barrier method along with oral contraceptives. PMID- 1610851 TI - Electrophysiologic properties of transplanted human heart with and without rejection. AB - Twelve male heart transplant recipients underwent routine electrophysiologic evaluation. None were taking cardioactive drugs, and only two had symptoms of arrhythmia. Two patients had endocardial VVI pacemakers because of previous early sinus node dysfunction. With simultaneous endomyocardial biopsy, we found seven patients with no evidence of rejection (group 1) and five patients with mild rejection (group 2; three initial or mild; two definite rejection). In two group 1 patients with presyncope, corrected sinus node recovery time was prolonged, and pacemakers were implanted into the endocardium. In all patients atrioventricular conduction was normal. One patient had evidence of functional duality of anterograde atrioventricular nodal conduction. In group 2 patients prolongation of effective refractory period of the donor atrium, functional refractory period of the atrioventricular node, and effective refractory period of the right ventricle were observed. This prolongation of refractoriness may be one of the earliest markers of rejection. PMID- 1610852 TI - Direct current catheter ablation of an accessory pathway in a recipient with refractory reciprocal tachycardia. AB - A recurrent reciprocating tachycardia developed in a 45-year-old man 2 years after heart transplantation. Electrocardiograms of both donor and recipient were normal, without patent preexcitation. An electrophysiologic study showed a left sided Kent bundle with only retrograde conduction property. Because antiarrhythmic therapy was unsuccessful, direct current catheter ablation was performed. Since this procedure the patient remained asymptomatic without antiarrhythmic therapy. PMID- 1610853 TI - Bradyarrhythmias requiring pacemaker implantation after orthotopic heart transplantation: association with rejection. AB - Patients with severe sinus-node dysfunction that required pacemaker implantation after orthotopic heart transplantation were reviewed. During a 21-month period, 42 transplantations were performed in 41 patients. Five patients (12.2%) required a permanent pacemaker because of severe dysrhythmias. Three patients had moderate to-severe cellular and/or humoral (vascular) rejection, and two of the five patients (40%) died. In the remaining two patients, bradyarrhythmias were due most likely to trauma to the sinus node during harvesting of the donor heart, and these patients have shown no evidence of significant rejection on repeated biopsies. A strong relationship was found between moderate or severe rejection and the development of significant bradyarrhythmias that required the placement of a permanent pacemaker. The development of severe dysrhythmias during the early or late posttransplantation period should be considered a manifestation of an ongoing rejection episode until proven otherwise. In our experience this evidence of rejection may imply a poor prognostic sign because it is associated with high mortality rates. PMID- 1610854 TI - Noninvasive radioisotopic diagnosis of acute heart rejection. AB - In a prospective protocol for noninvasive diagnosis and follow-up of acute heart rejection 162 examinations were performed in 36 patients who underwent heart transplantation. The follow-up period ranged from 15 days to 44 months. The protocol comprised multiple gated acquisition ventriculography with albumin labeled with 99mTc (740 MBq), acquired using a forward/backward by thirds framing mode, 32 frames/cycle, and 10 million total counts. Parameters of left ventricular diastolic function were analyzed. Antimyosin antibody labeled with indium 111 (74 MBq) was injected, and myocardium/lung uptake ratios were obtained at 48 hours in counts per pixel. Endomyocardial biopsy was performed in all patients within 48 hours. The results were evaluated by comparison of mean values of each parameter and global and individual correlation analysis in relation to the presence or absence of rejection and treatable (moderate or severe) or nontreatable (mild or absent) rejection. Antimyosin and diastolic function parameters showed significant differences (p less than 0.001) between patients with and without rejection and between patients with treatable and nontreatable rejection. Global correlation with biopsy existed (p less than 0.05) for antimyosin (r = 0.75), average filling rate (r = 0.61), and peak filling rate (r = 0.56). Individual correlation exhibited significance in all patients only for antimyosin (r = 0.78 to 0.98). In eight patients average filling rate also showed significant correlation (r = 0.65 to 0.88). In conclusion, these results provide a noninvasive diagnosis of cardiac allograft rejection episodes and allow an accurate selection between treatable and nontreatable rejection. Individual patient follow-up is possible with antimyosin. The study of diastolic function is also useful in this setting. PMID- 1610855 TI - Lymphocytic subsets and histopathologic changes associated with the development of heart transplant arteriosclerosis. AB - Transplantation of vascularized organ allografts is associated with the development of arteriosclerosis in the vessels of the donor graft. We have recently examined the distribution of lymphocytic/mononuclear inflammatory cell subsets and histopathologic changes seen in the sequential development of transplant arteriosclerosis in cardiac allografts exchanged between inbred rat strain combinations (LEW-to-F344) that differ for weak histocompatibility loci. The donor grafts were harvested at 7, 14, 21, 28, 50 to 65, and 90 days after transplantation, and the vascular lesions were characterized for the immunopathologic changes associated with the chronic rejection of the grafts. The inflammatory cell infiltration of the graft myocardium was present as early as 7 days after transplantation (53.37 +/- 9.06 inflammatory cells/high-power field), and the accumulation of cells increased at 3 and 4 weeks after transplantation (112.12 +/- 16.58 and 130.40 +/- 21.24 cells/high-power field, respectively). The infiltrating inflammatory cells in the grafts at 4 weeks after transplantation were predominantly ED-1+ macrophages (63.39%), with a substantial number of OX19+ T lymphocytes (28%), OX8+ Tc/s cells (25.4%), 3.2.3+ natural killer cells (16.89%), W3/25+ Th cells (20.2%), and a small number of OX33+ B lymphocytes (1.13%) and interleukin-2 receptor+ T lymphocytes (2.6%). Among the T-cell population, most (87.6%) were positive (R73+) for T-cell receptors. The arteriosclerotic lesions present in the cardiac grafts exhibited a gradual increase in severity of the vascular intimal proliferation and a similar pattern of increased intensity of cellular infiltration. The lesions were infiltrated with inflammatory cells beginning in the first week and increasing for the first month after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610856 TI - Correlation of endomyocardial biopsy findings with autopsy findings in human cardiac allografts. AB - To determine the reliability of endomyocardial biopsies in the detection of rejection, we took biopsy specimens from 22 autopsied human cardiac allografts by direct visualization. Five specimens were taken from each of four sites: left ventricular free wall, left ventricular septum, right ventricular free wall, and right ventricular septum. The findings in individual biopsy specimens and the summed diagnosis in the five biopsy specimens from each site were graded for rejection by a grading system similar to the Billingham criteria. Grading of the five specimens from each site also was done using criteria recommended by the International Society for Heart and Lung Transplantation. These findings were compared with the rejection grade determined by examination of large tissue sections from the autopsied hearts, used as the standard. Overall, X-Y correlation for single-specimen grading had an r value of 0.792. Grading based on five biopsy specimens from all sites using the modified Billingham criteria grading scheme had an r value of 0.845; the r value was 0.857 for the new grading system. Specificity of findings was high for all grades. Sensitivity of findings, however, was dramatically less for grades 1, 2, and 3. Predictive values for these grades also were less for grades 1, 2, and 3, but to a lesser degree than sensitivity. No difference in detection of rejection was found from specimens taken from different areas of the heart. We conclude that a significant number of hearts with middle grades of rejection may be underestimated by routine biopsies. The criteria for grading of the International Society for Heart and Lung Transplantation had a slight advantage over a more traditional grading system. PMID- 1610857 TI - Successful treatment of acute humoral rejection in a heart transplant patient. AB - Eight months after undergoing orthotopic heart transplantation, a patient had hypotension and biventricular heart failure. Endomyocardial biopsy specimens showed a modest cellular infiltrate, predominantly of plasma cells, and progressive myocyte injury, suggesting a humoral rejection process. The patient was treated with Minnesota antilymphoblast globulin and aggressively with plasmapheresis, resulting in evidence of myocyte repair, improved hemodynamics, and long-term survival. PMID- 1610859 TI - Cyclosporine blood monitoring after heart transplantation: a prospective comparison of monoclonal and polyclonal radioimmunoassays. AB - Management of heart transplant patients who are being given cyclosporine is complicated by the variety of methods available for measuring cyclosporine levels and the current trend toward exclusive use of monoclonal assays. To facilitate clinical decisions regarding cyclosporine levels when converting from a polyclonal system to monoclonal system, 79 heart transplant patients underwent a prospective study to compare the polyclonal radioimmunoassay with the monoclonal specific parent compound and nonspecific radioimmunoassays. Multivariable regression analyses were performed to generate best-fit equations for conversion of one assay to another. The closest correlation was noted in converting the measurement of cyclosporine parent compound with metabolites by the polyclonal method to the monoclonal method (nonspecific), R2 = 0.93. Considerable variability existed in the relationship between polyclonal and monoclonal specific levels (R2 = 0.66) and between monoclonal-nonspecific and monoclonal specific levels (R2 = 0.66), and both relationships were affected by hepatic function. Inferences: (1) The conversion of numeric cyclosporine levels from parent compound to parent plus metabolites is not completely predictable and must be empirically determined with the generation of appropriate regression equations. (2) Caution is advisable when a transplant team adopts a new cyclosporine assay for clinical use; formal study between existing assay methods and any newly adopted assay is warranted to prevent inadvertent underdosing or overdosing with cyclosporine. PMID- 1610858 TI - Origin of cells in the coronary intima during acute vascular rejection of the transplanted human heart. AB - Acute vascular rejection of the coronary arteries in human heart transplants is characterized by a lymphocytic infiltrate and a thickened intima that contains numerous highly vacuolated cells. The origin of the vacuolated cells has been controversial. In this immunocytochemical and electron microscopic study of four patients with acute vascular rejection, the predominant cells in the coronary artery intima were host-derived lymphocytes and highly vacuolated smooth muscle cells. Lymphocytic infiltrates were composed of T cells with variable numbers of B cells. Macrophages were infrequent. Smooth muscle cells were identified by their reactivity to muscle-specific actin and ultrastructural features of a peripherally displaced elongated nucleus associated with abundant myofibrils. In addition, the vacuolated cells did not react with endothelial factor 8-related antigen or Ulex europaeus agglutinin, as would be expected of endothelial cells. The cytoplasmic vacuoles present in the smooth muscle cells appear to be swollen endoplasmic reticulum containing watery fluid consistent with the hypothesis that they result from altered ion movement across the plasma membrane in response to cellular injury. PMID- 1610860 TI - Successful bridge to heart transplantation with a new left ventricular assist device. AB - During the last 5 years, a new pneumatically driven left ventricular assist device has been implanted in 18 heart transplantation candidates who required advanced mechanical circulatory support. The mean duration of support was 80 +/- 74 days, and the cumulative support time was 1400 days. Fifteen patients were successfully supported until the time of heart transplantation. As a result of early experience, in which three of four patients died after heart transplantation because their end-organ function failed to recover, subsequent efforts were made to institute support early, before irreversible organ damage occurred. Eleven of the 12 patients in the later experience are currently alive and well at a mean follow-up of 12.6 +/- 7.5 months. No thromboembolic episodes occurred, and minimal anticoagulation was required. Furthermore, patients were able to participate in rehabilitative exercise programs, thus optimizing their transplantation status. Finally, the findings in these patients have shown the feasibility of providing long-term, or even permanent, cardiac assistance. PMID- 1610861 TI - Surgical therapy for congestive heart failure: indications for transplantation versus cardiomyoplasty. AB - Heart transplantation is the procedure of choice for patients with severe congestive heart failure, but many patients are not candidates because of associated medical problems and the lack of donor hearts. Since 1988 we have performed 36 heart transplantations. One and 2-year actuarial survival rates have been 82% and 73%. Sixteen patients who were not candidates for heart transplantation have undergone cardiomyoplasty, a procedure in which the left latissimus dorsi is transposed to the myocardium and paced synchronously with the heart to augment cardiac function. The average age was 55 years (range, 39 to 65 years). Preoperative left and right ejection fractions were 24.9% +/- 2.1% and 43% +/- 4.5%. Eleven patients were in the New York Heart Association class IV, and five patients were in class III. Four operative deaths occurred, and three additional deaths occurred within 6 months of surgery. Nine patients became long term survivors, and seven of nine patients are alive at a mean follow-up of 29 months. All patients are in New York Heart Association class I or II. In long term survivors, mean left ventricular ejection fraction increased from 24.9% +/- 2.1% to 31.8% +/- 3.5% (p less than 0.01). All but one of the operative and early deaths occurred in patients with biventricular failure (n = 6). One operative death and no early deaths occurred in patients with normal right ventricular ejection fraction. This initial experience suggests that cardiomyoplasty may be helpful for heart failure patients with preserved right ventricular function, but heart transplantation should be the therapy of choice for biventricular failure. PMID- 1610862 TI - Bacterial mediastinitis after heart transplantation. AB - Bacterial mediastinal abscess or mediastinitis developed in nine (2.5%) of 361 consecutive patients who underwent isolated heart transplantation at the Texas Heart Institute. All nine patients had at least one predisposing factor that may have contributed to the development of mediastinitis. These included insulin dependent diabetes mellitus, repeat operation for postoperative mediastinal hemorrhage, Staphylococcus aureus pneumonitis, and cardiac allograft rejection in the early postoperative period (less than 30 days), necessitating steroid pulse therapy alone or in combination with murine-derived monoclonal antibody (OKT3). In six of the nine patients, the diagnosis of mediastinitis was made on the basis of clinical findings (unstable sternum and incisional erythema, with or without gross purulence), and in the other three patients, diagnosis was confirmed by computed tomography of the chest. Culture data were unequivocal in all patients; S. aureus was the most frequent (five patients), followed by S. epidermidis (two patients), and Enterobacter cloacae (two patients). Computed tomography-directed percutaneous drainage and systemic antibiotics were successful in treating two of three patients who had stable sternums with mediastinal abscess. In the remaining seven patients, sternal and mediastinal debridement with rewiring of the sternum was successfully applied. No patient required muscle or omental flap coverage, and no patient experienced a recurrence of mediastinitis during an average follow up period of 35 months (range, 12 to 46 months). PMID- 1610865 TI - Amiodarone-cyclosporine interaction in a heart transplant patient. AB - We report the case of a heart transplant patient whose cyclosporine clearance decreased by more than 50% after the institution of amiodarone therapy. This interaction necessitated a significant dosage reduction to maintain cyclosporine concentrations within the therapeutic range. To investigate the mechanism of the interaction, a cyclosporine-lipoprotein-binding determination was performed. The results suggest that drug displacement from competitive lipoprotein-binding sites is not responsible for the alterations in cyclosporine pharmacokinetics. Clearance data suggests, however, that the primary mechanism for the interaction is the inhibition cyclosporine metabolism by the cytochrome P-450 system. This report emphasizes the importance of reevaluating therapeutic drug regimens when new agents are added to prevent complications caused by drug interactions. If amiodarone and cyclosporine must be used concomitantly, cyclosporine levels must be monitored frequently, in anticipation of this interaction. PMID- 1610863 TI - Five-year follow-up of a randomized double-drug versus triple-drug therapy immunosuppressive trial after heart transplantation. AB - To determine the role of maintenance steroids in a cyclosporine and azathioprine immunosuppressive regimen, 112 heart transplant recipients were prospectively randomized to group I (n = 59; cyclosporine, azathioprine, and prednisolone) or group II (n = 53; cyclosporine and azathioprine). All patients received 7 days of induction with antithymocyte globulin. Patients receiving double-drug therapy who required four treatments for rejection were converted to maintenance steroids. This was necessary in 47% of the patients. Actuarial survival at 5 years was 82% in group I and 85% in group II. Linearized rejection in the first 3 months was lower with triple-drug therapy than with double-drug therapy (1.5 +/- 0.18 versus 2.3 +/- 0.23 episodes/100 patient days, p less than 0.01) but did not differ beyond 3 months. No significant differences were noted in 3-year left ventricular ejection fraction (0.56 +/- 0.09 versus 0.58 +/- 0.12 units), serum creatinine level (0.14 +/- 0.04 versus 0.14 +/- 0.03 mmol/L), or number with coronary artery disease (10 versus 13), diabetes, or bone complications. Patients receiving triple-drug therapy, however, had higher serum cholesterol level at 3 years (6.2 +/- 0.9 versus 5.4 +/- 1.2 mmol/L; p = 0.022) and required more antihypertensive agents (1.3 +/- 0.8 versus 0.8 +/- 0.6; p = 0.016). Similar trends emerged when patients receiving true double-drug therapy were compared with those patients who were "converted." Therapy with double versus triple immunosuppressive therapy results in similar 5-year survival and systolic function, using this protocol of converting recurrent rejectors on double-drug therapy to maintenance steroids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610864 TI - Prophylactic cytolytic therapy in heart transplantation: monoclonal versus polyclonal antibody therapy. AB - The value of immunoprophylaxis with monoclonal anti-CD3 antibodies (OKT3) was evaluated in 44 consecutive, nonrandomized heart transplant patients. The control group (n = 22) was treated with polyclonal rabbit antithymocyte globulin (RATG) for 5 days. The study group (n = 22) was treated with OKT3 for 14 days. All patients had identical perioperative immunosuppressive therapy and similar maintenance therapy, with cyclosporine, azathioprine, and low-dose prednisone (starting prednisone: OKT3 group immediately, RATG group 3 weeks [n = 11] or greater than 3 months [n = 11] after transplantation). The mean histologic rejection grade (Texas classification) in the RATG and the OKT3 groups was 2.5 +/ 1.9 and 0.6 +/- 0.8 (p less than 0.005) after 1 week and 4.3 +/- 1.6 and 2.0 +/- 1.5 (p less than 0.001) after 2 weeks, but there was no difference in the first year. The linearized rejection rate (rejections per 100 patient days) was higher in the RATG group in the first 2 weeks (2.6 vs 0, p less than 0.05 respectively, 7.8 vs 0.7, p less than 0.001) and higher in the OKT3 group in the second month (1.4 vs 2.8, p less than 0.01). In the RATG group the rejection rate fell continuously, to 0.1 at the end of the first year, whereas in the OKT3 group it remained 0.4 (NS). The cumulative first-year incidence was similar for persistent rejections (RATG 0.38 +/- 0.29 vs OKT3 0.48 +/- 1.13, NS) and insignificantly higher for severe rejections in the OKT3 group (RATG 0.21 +/- 0.32 vs OKT3 0.49 +/- 1.10). Rejection-related mortality in the first year was 0% (RATG) and 9% (OKT3).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610866 TI - A prospective randomized controlled trial of initial immunosuppression with ALG versus OKT3 in recipients of cardiac allografts. AB - Thirty-nine heart transplant recipients were randomized prospectively to receive OKT3 or antilymphoblast globulin (ALG) for 7 days, having otherwise identical protocols (group 1: OKT3, n = 20 patients; group 2: ALG, n = 19 patients). No preoperative immunosuppression was given. The protocol consisted of methylprednisolone, 500 mg intraoperatively, followed by 1 mg/kg/day, intravenously or orally, tapering to 0.2 mg/kg/day at 1 month; oral cyclosporine starting 3 to 5 days after transplantation; selective use of azathioprine, 1 to 4 mg/kg/day; and either OKT3, 5 mg/day for 7 days, or ALG, 15 mg/kg/day for 7 days. Of the 39 patients in the study, 34 are alive 6 months to 2 years after transplantation. The actuarial survival at 2 years for the OKT3 and ALG groups was 92% (+/- 0.07%) and 83% (+/- 0.09%), respectively (not significant [NS]). The time to first rejection for group 1 was 5.6 weeks and for group 2 was 5.3 weeks (NS). The mean number of rejections for group 1 and group 2 was 2.1 episodes per patient and 1.4 per patient, respectively (NS). Three patients in each group were free of rejection at 6 months. The total number of infections at 6 months was 1.05 per patient in group 1, 0.74 per patient in group 2 (NS), with 35% of patients receiving OKT3 and 52% of patients receiving ALG actuarially free of infection by 6 months after surgery (NS). During the first 24 hours after surgery, no significant differences were noted in mean blood pressure, central venous pressure, or Po2 between the groups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610867 TI - Single lung transplantation for severe emphysema. AB - Lung transplantation is effective therapy for patients with severe obstructive lung disease. We reviewed seven patients with severe emphysema (age, 48 +/- 5 years; forced expiratory volume in 1 second [FEV1] 0.76 +/- 0.26 liters) who received single-lung transplants (SLT) at our institution between August 1989 and September 1990. Studies to assess the adequacy of cardiac function before transplantation showed moderately reduced right ventricular function (by multiple gated acquisition, 34 +/- 6%), moderately elevated pulmonary artery pressure (25 +/- 3 mm Hg), and normal left ventricular function (by multiple gated acquisition 65% +/- 12%) and coronary arteriograms. Time on the waiting list before transplantation was reduced compared with heart-lung transplant (HLT) recipients (waiting time, 2.9 +/- 1.5 months for SLT, 9.6 +/- 10.2 months for HLT). Six of the SLT recipients are currently alive (after transplantation interval, 17 +/- 5 months); the remaining recipient died of pulmonary embolism 21 days after SLT. Number of ventilator days, intensive care unit days, and days to hospital discharge after transplantation did not differ significantly from HLT recipients. Cardiopulmonary bypass was necessary in four SLT recipients. Pulmonary function was markedly improved after SLT (FEV1, 1.78 +/- 0.73 L/min after SLT versus 0.75 +/- 0.3 L/min before SLT; p less than 0.01), and functional status is correspondingly improved. CONCLUSIONS: SLT constitutes effective therapy for patients with severe emphysema, including those with moderate reduction of right ventricular function; and SLT offers distinct advantages over HLT, including decreased waiting time before transplantation, improved donor organ utilization, and less frequent need for cardiopulmonary bypass. PMID- 1610868 TI - Renal, hemodynamic, and electrocardiographic effects of low versus high osmolality contrast agents on the transplanted heart. AB - The effects of low and high osmolality ionic contrast agents on the transplanted heart were studied in 75 consecutive patients. Renal function remained unchanged 24 hours after coronary angiography in both groups. Hemodynamic changes were transient and more pronounced after administration of the high osmolality agent; ECG changes and cineangiography quality were similar after both agents. The manyfold increase in cost of the low osmolality contrast agents may not be justified for use in stable patients after heart transplantation. PMID- 1610870 TI - Undifferentiated vascular endothelial and inflammatory cells in vascular rejection. PMID- 1610869 TI - Chylopericardium after orthotopic heart transplantation. AB - Chylopericardium is an infrequent cause of pericardial effusions after heart surgery and to our knowledge has not been reported after orthotopic transplantation. We report the occurrence of chylopericardium in a heart transplant recipient who was successfully treated with a pericardial window, pericardiocentesis, and a diet rich in medium-chain triglycerides. PMID- 1610871 TI - The structure of Photosystem I from the thermophilic cyanobacterium Synechococcus sp. determined by electron microscopy of two-dimensional crystals. AB - The structure of the Photosystem I (PS I) complex from the thermophilic cyanobacterium Synechococcus sp. has been investigated by electron microscopy and image analysis of two-dimensional crystals. Crystals were obtained from isolated PS I by removal of detergents with Bio-Beads. After negative staining, either single layers or two superimposed layers with a rotational different orientation were observed. The layers have a rectangular unit cell of 16.0 x 15.0 nm, which contains two PS I monomers. The monomers are arranged alternating up and down in each layer. For double-layer crystals, the images of the two layers could be separately processed by a combination of Fourier-peak-filtering and correlation averaging. Features in the two-dimensional plane can be seen with a resolution up to 1.5-1.8 nm. A model for the PS I structure was obtained by combining three dimensional reconstructions from three tilt-series. The model shows an asymmetric PS I complex. On one side (presumably the stromal side) there is a 3 nm high ridge. This is most likely comprised of the psaC, psaD and psaE subunits. The other side (presumably the lumenal side) is rather flat, but in the center there is a 3 nm deep indentation, which possibly separates partly the two large subunits psaA and psaB. PMID- 1610872 TI - Creatine kinase binding and possible role in chemically skinned guinea-pig taenia coli. AB - The activity and role of creatine kinase (CK) associated with contractile proteins of smooth muscle have been investigated using skinned guinea-pig taenia coli fibers. Total CK activity was 163 +/- 22 IU/g (ww) and agarose electrophoresis showed BB, MB, and MM isoforms (BB-CK being the predominant isoenzyme). After skinning for 1 h with Triton X-100, BB-CK was specifically associated with the myofibrils, representing 22% of the preskinned CK activity. When relaxed fibers were exposed to pCa 9 in the presence of 250 microM ADP, 0 ATP and 12 mM PCr, tension was not significantly different from resting tension, but changing to pCa 4.5 caused the fibers to generate 59.1 +/- 5.2 percent of maximal tension. When a high-tension rigor state was achieved (250 microM ADP, 0 ATP, 0 PCr, and pCa 9), the addition of 12 mM PCr effected significant relaxation. These observations implicate an endogenous form of BB-CK, associated with the myofilaments and capable of producing enough ATP for submaximal tension generation and significant relaxation from rigor conditions. It was also shown that ADP is bound to the myofibrils and available for rephosphorylation by BB-CK. These results suggest co-localization of ATPase, MLCK and CK on the contractile proteins of the taenia coli. This enzymic association may play a role in the compartmentation of adenine nucleotides in smooth muscle. PMID- 1610873 TI - Multichannel circular dichroism investigations of the structural stability of bacterial cytochrome P-450. AB - The thermal unfolding of cytochrome P-450 LIN and P-450 CAM measured in presence and absence of their specific substrates was analyzed by circular dichroism (CD) and the alpha-helix content was estimated. Both proteins show, independent of the presence or absence of the substrates, nearly the same amount of loss of the CD in the peptide region. The comparison of the half transition temperatures determined from different chromophores and different methods indicates a non-two state transition of the thermal unfolding. For such analysis we developed a new spectrometer, which is capable of measuring the CD simultaneously at all wavelengths in a limited wavelength region. PMID- 1610874 TI - The ionic strength of the intermembrane space of intact mitochondria is not affected by the pH or volume of the intermembrane space. AB - Ionic strength affects the electron transport activity of cytochrome c through its electrostatic interactions with redox partners and membrane lipids. We previously reported (Cortese, J.D., Voglino, A.L. and Hackenbrock, C.R. (1991) J. Cell Biol. 113, 1331-1340) that the ionic strength (I) of the intermembrane space (IMS-I) in isolated, intact condensed mitochondria is similar to the external, bulk I, over a wide range of bulk I. We now consider the possible effects of IMS pH and IMS-volume, both variable parameters of mitochondrial function in situ, on IMS-I. IMS-pH and IMS-I were measured with pH- and I-sensitive fluorescent probes (highly fluorescent FITC-dextran for IMS-pH and FITC-BSA for IMS-I). These probes were delivered into the IMS of intact mitochondria via probe encapsulation into asolectin vesicles, followed by low pH-induced fusion of the vesicles with the outer membranes of intact mitochondria. IMS-pH was found to be 0.4-0.5 units lower than bulk pH over the pH range 6.0-8.5 for mitochondria with a large IMS volume separating the two mitochondrial membranes (condensed configuration), and 0-0.2 units lower for mitochondria with a small IMS-volume and membranes closely opposed (orthodox configuration). This small pH difference between IMS-pM and bulk pH did not influence the similarity between IMS-I and bulk I. When the IMS volume was osmotically decreased, bringing the two mitochondrial membranes in close proximity as in the orthodox configuration, IMS-I followed the bulk I above 10 mM but did not respond to changes in bulk I below 10 mM. The lack of response of the IMS-I below 10 mM indicates that the close proximity of the two mitochondrial membranes excludes ions only at low, nonphysiological I. Since the similarity of IMS-I and bulk I is unaffected by either IMS-pH or IMS-volume above a bulk I of 10 mM, at cytosolic physiological I (i.e., 100-150 mM) cytochrome c can be expected to be a free, three-dimensional diffusant in the IMS irrespective of the pH or volume of the IMS. PMID- 1610875 TI - Malate dehydrogenase isoenzymes: cellular locations and role in the flow of metabolites between the cytoplasm and cell organelles. AB - Malate dehydrogenases belong to the most active enzymes in glyoxysomes, mitochondria, peroxisomes, chloroplasts and the cytosol. In this review, the properties and the role of the isoenzymes in different compartments of the cell are compared, with emphasis on molecular biological aspects. Structure and function of malate dehydrogenase isoenzymes from plants, mammalian cells and ascomycetes (yeast, Neurospora) are considered. Significant information on evolutionary aspects and characterisation of functional domains of the enzymes emanates from bacterial malate and lactate dehydrogenases modified by protein engineering. The review endeavours to give up-to-date information on the biogenesis and intracellular targeting of malate dehydrogenase isoenzymes as well as enzymes cooperating with them in the flow of metabolites of a given pathway and organelle. PMID- 1610876 TI - The relation between the soluble factor associated with H(+)-transhydrogenase of Rhodospirillum rubrum and the enzyme from mitochondria and Escherichia coli. AB - Although in mitochondria, Escherichia coli and Rhodobacter capsulatus the H(+) transhydrogenases are intrinsic membrane proteins, in Rhodospirillum rubrum a water-soluble component (Ths) and a membrane-bound component are together required for activity. Ths was selectively removed from chromatophore membranes of Rhs. rubrum and was purified to homogeneity by precipitation with (NH4)2SO4 and ion-exchange, affinity dye and gel exclusion chromatography. The latter indicated an Mr of approx. 74,000 under non-denaturing conditions but analysis of the pure protein by SDS-PAGE revealed a single polypeptide, Mr 43,000. Antibodies against this polypeptide inhibited transhydrogenase activity of chromatophores and decreased the capacity of Ths to restore activity to depleted membranes. They reacted with a polypeptide of Mr 43,000 in crude cell extract, chromatophore membranes and chromatophore washings but not with transhydrogenase polypeptides from the membranes of E. coli, Rb. capsulatus or animal mitochondria. The N terminal amino acid sequence of the 43,000 polypeptide was strongly homologous with the reported N-terminal regions of mitochondrial transhydrogenase and the alpha subunit of the E. coli protein. The break between the alpha and beta polypeptides of E. coli transhydrogenase is such that both components are membrane-associated. In contrast, these results suggest that in the Rhs. rubrum enzyme Ths has been formed by a break closer to the N-terminus, thus avoiding the putative trans-membrane helical segments and yielding a relatively hydrophilic subunit, which is water-soluble. There is a predicted similarity between Ths and the reported sequence of alanine dehydrogenase from Bacillus but Ths did not have any alanine dehydrogenase activity. PMID- 1610877 TI - Structural studies of a phosphocholine substituted beta-(1,3);(1,6) macrocyclic glucan from Bradyrhizobium japonicum USDA 110. AB - In our previous in vivo 31P study of intact nitrogen-fixing nodules (Rolin, D.B., Boswell, R.T., Sloger, C., Tu, S.I. and Pfeffer, P.E., 1989 Plant Physiol. 89, 1238-1246), we observed an unknown phosphodiester. The compound was also observed in the spectra of isolated bacteroids as well as extracts of the colonizing Bradyrhizobium japonicum USDA 110. In order to characterize the phosphodiester in the present study, we took advantage of the relatively hydrophobic nature of the material and purified it by elution from a C-18 silica reverse-phase chromatography column followed by final separation on an aminopropyl silica HPLC column. Structural characterization of this compound with a molecular weight of 2271 (FAB mass spectrometry), using 13C-1H and 31P-1H heteronuclear 2D COSY and double quantum 2D phase sensitive homonuclear 1H COSY NMR spectra, demonstrated that the molecule contained beta-(1,3); beta-(1,6); beta-(1,3,6) and beta-linked non-reducing terminal glucose units in the ratio of 5:6:1:1, respectively, as well as one C-6 substituted phosphocholine (PC) moiety associated with one group of (1,3) beta-glucose residues. Carbohydrate degradation analysis indicated that this material was a macrocyclic glucan, (absence of a reducing end group) with two separated units containing three consecutively linked beta-(1,3) glucose residues and 6 beta-(1,6) glucose residues. The sequences of beta-(1,3)-linked glucose units contained a single non-reducing, terminal, unsubstituted glucose linked at the C-6 position and a PC group attached primarily to an unsubstituted C-6 position of a beta-(1,3)-linked glucose. PMID- 1610878 TI - In vitro calcium deposition by rachitic rat matrix vesicles: nucleoside triphosphate supported calcium deposition. AB - The present study was designed to test whether ATP at serum levels can support matrix vesicle-mediated Ca deposition while the final Ca x P ion product is maintained at or below serum or cartilage fluid levels. Rachitic rat epiphyseal cartilage matrix vesicles (40 micrograms protein/ml) in a simple calcifying solution (without exogenously added Pi) containing 50 mM Tris, pH 7.6 at 37 degrees C, 0.1 M NaCl, 1.35 mM CaCl2, 1 mM ATP, deposited about 500 nmol Ca/mg protein after 5 h. The amount of Ca deposited increased with increases in incubation time, concentrations of ATP, Ca2+, hydroxide, and matrix vesicle protein. UTP, GTP, and CTP were equally effective in supporting Ca deposition by matrix vesicles. ATP-alpha,beta-methylene and ATP-beta,gamma-methylene were inhibitory for ATP-dependent Ca deposition. Experiments with limiting amounts of ATP and Ca2+ available in the calcifying solution indicated that ATP concentration at serum levels, in the presence of Ca x P ion products at serum or cartilage fluid levels, can support matrix vesicle-mediated Ca deposition. PMID- 1610879 TI - Interaction of dipyridamole with micelles of lysophosphatidylcholine and with bovine serum albumin: fluorescence studies. AB - The interaction of the coronary vasodilator dipyridamole with biological systems, protein and membranes has been studied through optical absorption and fluorescence spectroscopies. Using the analysis of the spectra and fluorescence intensity of dipyridamole (DIP) in solution, the interaction of this compound with the transport protein albumin (BSA) and with a model of cell membranes, namely micelles of lysophosphatidylcholine (L-PC), was investigated. Measurements were performed at pH 5.0 and pH 7.0 where the molecule of DIP is fully protonated and partially protonated, respectively. The quenching of fluorescence with nitroxide-stable radicals 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) and 4 hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) as well as with acrylamide and iodide allowed the localization of the drug in the polar interface of micelles. Quenching by acrylamide and iodide in L-PC micelles demonstrated the effect of micelle protonation which increased the accessibility of iodide to the chromophore. An effective association constant was obtained both at pH 7.0 (7.5 x 10(3) M-1) and pH 5.0 (2.5 x 10(3) M-1) and a very good agreement with the proposed binding model was observed. The quantum yields of fluorescence data agree very well with the fluorescence lifetimes. The measurement of lifetimes was important to understand the kinetic data obtained from Stern-Volmer plots both of radical, acrylamide and iodide quenching of fluorescence. It was observed that, in the presence of micelles, the kq value increased for TEMPO while decreased for TEMPOL. This result, together with the vanishing solubility of DIP in saturated hydrocarbons and the preferential partition of TEMPO in micelles, suggested the localization of DIP in the polar micellar interface. This is also supported by the enhanced iodide quenching at pH 5.0, constancy of acrylamide quenching in the range of pH 7.0-5.0 and the partition of TEMPO and TEMPOL in SDS micelles. The association constant of DIP to BSA was also estimated both at pH 7.0 (2 x 10(4) M 1) and pH 5.0 (4 x 10(3) M-1). Quenching studies with nitroxide radicals, acrylamide and iodide also suggested the binding of the drug to a hydrophobic region of the protein. At pH 5.0, the protein undergo a conformational change which leads to a loosening of the overall structure so that the accessibility of the nitroxide radicals for DIP is increased at this pH. The differences in kq values at pH 7.0 and pH 5.0 suggested that at pH 7.0 the chromophore is protected in the protein site.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1610880 TI - Developmental changes in the amount and functional state of UDP glucuronosyltransferase. AB - The effect of postnatal development on the activity of liver microsomal UDP glucuronosyltransferase was determined in male Wistar rats between 25 and 200 days of age using p-nitrophenol as aglycone. Enzyme activity (measured at 1.0 mM UDP-glucuronic acid, 0.05 mM p-nitrophenol) decreased 55% between 25 and 88 days of age and was constant thereafter. Treatment of microsomes with palmitoyl lysophosphatidylcholine, which allows for an estimation of the amount of enzyme, showed approximately a four-fold decrease in enzyme concentration during the same period. This decrease was confirmed by Western blotting of microsomes with anti UDP-glucuronosyltransferase antiserum. The fact that a nearly four-fold decline in enzyme concentration led to only a 55% decrease in activity indicates that there was an increase in activity per molecule of UDP-glucuronosyltransferase as the concentration of enzyme decreased. Treatment of microsomes with high pressure or detergent caused a greater extent of enzyme activation in microsomes prepared from 25 than 200 day old rats, suggesting that a fraction of the enzyme in older rats was activated in untreated microsomes. Fatty acid analysis of liver microsomal lipids during postnatal development revealed changes in docosahexaenoic acid (22:6) which correlated with levels of UDP glucuronosyltransferase activity. PMID- 1610881 TI - Iron-transferrin binding to isolated guinea pig enterocytes and the regional localisation of intestinal iron transfer during ontogeny. AB - Neonatal animals are iron replete but in comparison with adults they display increased intestinal iron absorption. In order to examine possible mechanisms for this developmental adaptation we have measured the appearance of iron in peripheral blood following 30 min exposure of duodenal and ileal segments of adult and neonatal guinea pigs in vivo to 59Fe-ascorbate. Parallel experiments have determined the kinetics of 125I-labelled diferric transferrin binding to villus enterocytes isolated from duodenum and ileum. In adult animals the rate of appearance of 59Fe in peripheral blood was 11-fold greater following duodenal, compared to ileal exposure to the radioligand. No such regional difference was detected in the neonate. Isolated cells showed saturable binding of [125I]transferrin which was maximal between 30 and 60 min. The kinetics of specific transferrin binding by adult duodenal and ileal enterocytes were similar and were also not significantly different to respective values in neonatal duodenal and ileal cells. Thus, it is likely that increased iron absorption in the neonate is due in part to enhanced ileal iron transfer. The interaction of transferrin with its receptor, however, is not involved in this developmental change in uptake. PMID- 1610882 TI - An enzyme immunoassay for the measurement of human monoamine oxidase B protein. AB - A heterologous, competitive, solid phase ELISA has been developed which can measure monoamine oxidase (MAO) B concentration (both inactive and active) in human platelets and other tissue extracts. The assay is based on competition between a soluble form of MAO and MAO bound to a solid phase for binding to a limiting amount of a MAO B-specific monoclonal antibody, 3F12/G10. It utilises a crude and easily prepared sample of human liver mitochondrial membranes as the source of solid phase MAO. Optimal assay conditions allow detection of MAO B down to at least 0.5 ng (4.18 fmol; 6.25 ng/ml) of protein. As the assay is sensitive and simple to operate, it will allow a systematic assessment of the role of platelet MAO concentrations in the aetiology of psychiatric and neurologic conditions. PMID- 1610883 TI - Characterization of a 67 kDa microtubule-binding protein in the pancreas from different species. AB - Microtubule-interacting proteins have been studied from a pancreas supernatant. These proteins were first identified by affinity chromatography on taxol stabilized microtubules. Among these interacting polypeptides, we show, for the first time, the presence of a protein which has a molecular mass of 67 kDa, as determined by polyacrylamide slab gel electrophoresis. The heat stability and the ability of this 67 kDa polypeptide to copolymerize with phosphocellulose-purified tubulin suggest that this protein may be a microtubule-associated protein. PMID- 1610884 TI - The metabolism of fructose in the bivascularly perfused rat liver. AB - The metabolism of fructose was investigated in the bivascularly and hemoglobin free perfused rat liver. Anterograde and retrograde perfusions were performed. In anterograde perfusion, fructose was infused at identical rates (19 mumols min-1 g 1) via the portal vein (all liver cells) or the hepatic artery (predominantly perivenous cells); in retrograde perfusion fructose was infused via the hepatic vein (all liver cells) or the hepatic artery (only periportal cells). The cellular water spaces accessible via the hepatic artery were measured by means of the multiple-indicator dilution technique. The following results were obtained. (i) Fructose was metabolized to glucose, lactate and pyruvate even when this substrate was infused via the hepatic artery in retrograde perfusion; oxygen consumption was also increased. (ii) When referred to the water spaces accessible to fructose via the hepatic artery in each perfusion mode, the rate of glycolysis was 0.99 +/- 0.14 mumols min-1 ml-1 in the retrograde mode; and, 2.05 +/- 0.19 mumols min-1 ml-1 in the anterograde mode (P = 0.002). (iii) The extra oxygen uptake due to fructose infusion via the hepatic artery was 1.09 +/- 0.16 mumols min-1 ml-1 in the retrograde mode; and, 0.51 +/- 0.08 mumols min-1 ml-1 in the anterograde mode (P = 0.005). (iv) Glucose production from fructose via the hepatic artery was 2.18 +/- 0.18 mumols min-1 ml-1 in the retrograde mode; and, 1.83 +/- 0.16 mumols min-1 ml-1 in the anterograde mode (P = 0.18). (v) Glucose production and extra oxygen uptake due to fructose infusion did not correlate by a single factor in all perfusion modes. It was concluded that: (a) rates of glycolysis are lower in the periportal area, confirming previous views; (b) extra oxygen uptake due to fructose infusion is higher in the periportal area; (c) a predominance of glucose production in the periportal area could not be demonstrated; and (d) extra oxygen uptake due to fructose infusion is not a precise indicator for glucose synthesis. PMID- 1610885 TI - Growth related changes to functional parameters in the bovine lens. AB - Dimensions, volumes and protein contents were measured for bovine lenses with wet weights ranging from 0.17-3.07 g (2 months gestation to 19 years post-natal). All increase in a non-linear fashion. The lens becomes flatter with age due to a more rapid increase in the equatorial plane, but the ratio of anterior to posterior sagittal distances remains constant (1.19). The radius of curvature increases from 4.9 to 15 for the anterior surface and from 4.4 to 13 for the posterior. Protein content increases more rapidly than volume resulting in an increased average protein concentration from around 18% in the early prenatal lens to nearly 50% in the 19 year old. Total protein content (TPC) was found to be related to wet weight (We) according to the equation, TPC = 0.3We1.33. It is suggested that TPC is a better parameter for describing growth than wet weight or age. The refractive index, in the equatorial plane, increases towards the centre, from 1.38 at the edge of the lens. The maximum index, in the centre, increases with lens size up to 1.474 in the largest lens studied. This corresponds to a protein concentration of 70%. In all lenses, refractive index and protein concentration gradients were superimposable when plotted from the outside towards the centre. The optical performance of the lenses was assessed by measuring the back focal length which increases gradually from 24 to 51.5 mm over the 0.17 to 3.07 g size range. This was attributed to the increased radii of curvature. PMID- 1610886 TI - Photodynamic degradation of vitamin E induced by psoralens. AB - Psoralens and other furocoumarins currently used in PUVA photochemotherapy are shown to have, to a variable extent, the ability to hasten the rate of ultraviolet-induced photooxidation of alpha-tocopherol (alpha-T) in ethanol or ethanol-phosphate buffer (pH 6.8). The sensitizing effect varies significantly with the substrate concentration and the nature of the furocoumarin used, and is dependent on the presence of oxygen. Scavengers of singlet oxygen, e.g., sodium azide, markedly inhibit the psoralen-sensitized photooxidation of alpha-T, whereas superoxide dismutase exerts an opposite, accelerating effect on the reaction rate. Catalase has no significant influence on the kinetics of alpha-T decay. Analysis of the products formed by psoralen-sensitized photooxidation of alpha-T in ethanol-phosphate buffer showed the presence of alpha tocopherolquinone, its 2,3-epoxide and two related compounds containing the 7 oxaspiro[4.5]dec-1-ene-3,6-dione ring system. The nature of these products, coupled with the results of the kinetic experiments, suggest that psoralens induce a type II, oxygen-dependent photodegradation of alpha-T primarily mediated by singlet oxygen. PMID- 1610887 TI - Study of water and oil diffusion in rape seeds with sorption-desorption and NMR techniques. AB - The sorption and desorption of water in rape seeds was measured. From the sorption isotherm it follows that for water content greater than about 6% the water molecules tend to form clusters. The mutual diffusion coefficient of water into and out of the seeds was determined from the time dependence of sorption and desorption. There is a pronounced hysteresis in the sorption-desorption process, desorption proceeds faster than sorption. The self-diffusion of water (at maximum humidity of the seeds) and oil within the seeds was investigated by the pulsed field gradient NMR. The measurement of oil self-diffusion shows restricted diffusion of the oil within droplets and allows the determination of the droplet radii and their distribution width. PMID- 1610888 TI - The distribution of enzymes involved in purine metabolism in rat kidney. AB - Adenosine produced from 5'-AMP has been proposed as a mediator of intrinsic renal regulation. The rates of 5'-AMP and adenosine metabolism are dependent on the activities of enzyme involved in purine metabolism. The activities of adenosine kinase (AK), adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), AMP deaminase, xanthine oxidase and purine nucleoside phosphorylase were measured in cytosolic and membrane fractions from glomeruli, cortical tubules, medullary thick ascending limb of Henle (MTAL) and collecting duct prepared from rat kidney by combinations of sieving and sucrose density gradient centrifugation techniques. In the cytoplasm of glomeruli cells, the activity ratios of ADA/AK and AMP deaminase/5'-NT were 70 and 2.4, respectively. The highest activity of 5'-NT was found in membrane fractions of cortical tubules where it was equally distributed between luminal and antiluminal membranes. Membrane fractions of MTAL did not contain detectable amounts of adenosine deaminase activity. The highest activity of xanthine oxidase and purine nucleoside phosphorylase was in the cytoplasm fraction of glomeruli. These results suggest that deamination of AMP and adenosine may be favored in the cytoplasm of glomeruli cells. In contrast, in the extracellular space of glomeruli and especially in the cortical tubule, AMP can be converted preferentially to adenosine by 5'-NT. PMID- 1610889 TI - Increased epsilon(gamma-glutamyl)lysine crosslinking associated with increased protein synthesis in the inner layers of healing rat skin wounds. AB - Three days after biopsy wounds were made in the dorsal skin of rats the animals were killed and explants of wounded and unwounded skin were incubated for 7 h with either [3H]glutamine or [3H]lysine. Both incubated and fresh control explants were then dissected into three layers which were homogenized, extracted, digested and then assayed for epsilon (gamma-glutamyl)lysine. The concentration of epsilon(gamma-glutamyl)lysine was greater in all three wounded layers than in the corresponding unwounded layers. The concentration in the wounded middle (dermal) layer and in the unwounded middle layer of younger rats was greater than in the unwounded outer (keratinized) layer, which has previously been shown to contain epsilon(gamma-glutamyl)lysine crosslinks. The incorporation of label from both [3H]glutamine and [3H]lysine into buffer-insoluble protein of the middle and inner (muscle) layers was much greater in the wounded explants than in the unwounded. Except for [3H]lysine in the inner layer there was also an increase in the fraction of incorporated label which was converted to epsilon(gamma glutamyl)lysine. These results show that increased protein biosynthesis during repair in the wounded explants is associated with increased formation of epsilon(gamma-glutamyl)lysine. In addition, they indicate that the crosslink is involved in some process in the middle and inner layers which is distinct from its known function in keratinization of the epidermis. PMID- 1610890 TI - On the specificity of the D-galactose-binding lectin (PA-I) of Pseudomonas aeruginosa and its strong binding to hydrophobic derivatives of D-galactose and thiogalactose. AB - The D-galactose-binding lectin (PA-I) from the bacterium Pseudomonas aeruginosa, isolated by affinity chromatography on Sepharose, was examined for its relative affinities for simple sugars and their derivatives using equilibrium dialysis and hemagglutination inhibition tests. The lectin, which was found to bind 0.68 mol of D-galactose per subunit of 12.8 kDa, exhibited an association constant (Ka) of 3.4 x 10(4) M-1 for D-galactose and higher affinities for hydrophobic and thio derivatives of D-galactose (with highest affinity for the hydrophobic thio derivatives). alpha-Methyl-galactoside was a stronger inhibitor than the beta methyl derivative and alpha-lactose was a weak inhibitor but the hydrophobic phenylated derivatives of the beta-configuration of D-galactose were more potent inhibitors than the respective alpha-galactosides. PMID- 1610891 TI - Straightening out the bends in curved DNA. PMID- 1610892 TI - Ferritin mRNAs on rat liver membrane-bound polysomes synthesize ferritin that does not translocate across membranes. AB - Ferritin is a typical intracellular protein but small amounts are also present in serum and other biological fluids. The source and physiological significance of serum ferritin are still obscure. The presence of ferritin mRNAs on polysomes bound to endoplasmic reticulum (ER) could be relevant for the secretion of ferritin. By Northern blot analysis we found significant amounts of both L and H subunit mRNAs on rat liver membrane-bound polysomes. Immunoprecipitation of translational products of membrane-bound polysomes with anti-rat liver ferritin antibody showed that ferritin is actually synthesized on ER membranes. Analysis of RNA extracted from salt-washed rat liver microsomes demonstrated that ferritin mRNAs are translated by polysomes tightly bound to ER membranes. Following iron treatment, both the amount of H and L subunit mRNAs and ferritin synthesis increased sharply in both free and bound polysomal fractions. Translation of membrane-bound polysomes in the presence of microsomal membranes indicated that ferritin is not processed by signal sequence cleavage or glycosylation and is not translocated into ER membranes. Ferritin mRNAs found on membrane-bound polysomes are associated with ER in a specific way, however, their products do not seem to follow the classic secretory pathway and therefore the significance of the large amount of ferritin mRNAs in the bound ribosome fraction remains unclear. PMID- 1610893 TI - Histone H4 mRNA levels are down-regulated by 3' RNA processing during terminal differentiation of myoblasts. AB - The capacity for 3' processing of the histone H4 pre-mRNA is lost following differentiation of rat L6 myoblasts to myotubes. Nuclear extracts prepared from proliferating myoblasts, but not differentiated myotubes, actively process histone H4 pre-mRNA in vitro. The activity of two factors required for 3' processing, the heat-labile factor and U7 snRNP, also changes during the differentiation period, concurrent with the loss of 3' processing activity. During myotube formation, the activity of the heat-labile factor decreases significantly while the 5' sequences of the U7 snRNA become progressively resistant to micrococcal nuclease digestion. Thus, the dramatic down-shift in histone H4 mRNA levels which occurs during myoblast differentiation is controlled at both the transcriptional and posttranscriptional level. PMID- 1610894 TI - Differential regulation of kininogen gene expression by estrogen and progesterone in vivo. AB - Kininogens which have multifunctional domains, serve as the precursors of potent vasoactive kinin peptides and also function as cysteine proteinase inhibitors. Given its potential role in blood pressure homeostasis and inflammation, we have examined the regulation of rat kininogen gene expression by sex hormones in vivo. Our studies indicate a differential regulation of kininogen gene expression in rat liver by estrogen and progesterone. Northern and dot blot analysis using a rat low molecular weight kininogen cDNA probe show that kininogen mRNA levels in the liver of female rats are 4-fold higher than those in male rats. Ovariectomy results in a reduction of kininogen transcripts in the liver, while estradiol replacement of the ovariectomized rats increases kininogen mRNA levels. Similarly, Northern blot analysis using a kallikrein cDNA probe shows that estradiol treatment induces an increase of kallikrein gene expression in the kidney of the same animals. In contrast, progesterone treatment of the ovariectomized rats results in an increase in renal kallikrein mRNA levels while it reduces kininogen gene expression as compared to vehicle-treated ovariectomized animals. Immunoreactive kininogen levels in the serum, analyzed by a direct radioimmunoassay and Western blot, are increased by estradiol but slightly decreased by progesterone treatment. Western blot of serum proteins on a two-dimensional polyacrylamide gel reveals that in estradiol-treated ovariectomized rats, the levels of several 68,000 Da kininogens varying in charge are markedly higher than those in ovariectomized rats. The results indicate that estrogen is one of the determinants in regulating low molecular weight kininogen gene expression in vivo. The impact of estrogen-regulated kininogen expression on cardiovascular function awaits further investigation. PMID- 1610895 TI - Expression of Xenopus laevis histone H5 gene in yeast. AB - As an approach to assess linker histone function, we engineered a cDNA encoding Xenopus laevis histone H5 (XLH5), into the yeast Saccharomyces cerevisiae, which lacks any known proteins homologous to linker histones. XLH5 cDNA when fused to the yeast GAL10 promoter and 5' untranslated region (UTR) was shown to be accurately transcribed at relatively high levels in cells harvested at mid to late log after exposure to at least 22 mM galactose. The resultant 0.95 kb XLH5 transcript reached steady state levels by approx. 2 h after galactose induction. In contrast, the product, detected by anti-XLH5 antibody, was not stably expressed until 4 h or more after induction, when no apparent growth takes place. The expression product was 27% smaller than native H5 and may have been proteolytically processed. Constitutive transcription and loss of XLH5 expression product occurred using a plasmid construct containing a 275 bp fragment of the pBR322 tetr gene inserted downstream of the GAL10 promoter. This fragment carries a putative yeast cell-type-specific upstream activation sequence. PMID- 1610896 TI - Molecular cloning and expression in Escherichia coli of a cDNA clone encoding luciferase of a firefly, Luciola lateralis. AB - We have cloned a cDNA encoding Luciola lateralis (a common firefly in Japan) luciferase from a cDNA library of lantern poly(A)+ RNA, using a cDNA of L. cruciata (another common firefly in Japan) luciferase as a probe. The primary structure of L. lateralis luciferase deduced from the nucleotide sequence was shown to consist of 548 amino acids with a molecular weight of 60,132. Sequence comparison indicates that L. lateralis luciferase has significant sequence identity (94%) to L. cruciata luciferase, and that it has less sequence similarity (67%) to Photinus pyralis (a North American firefly) luciferase. The isolated cDNA clone, when introduced into Escherichia coli, directed the synthesis of enzymatically active luciferase under the control of the lacZ promoter. PMID- 1610897 TI - Differential regulation of heme oxygenase isozymes by Sn- and Zn-protoporphyrins: possible relevance to suppression of hyperbilirubinemia. AB - Synthetic metalloporphyrins decrease heme oxygenase (HO)-dependent bilirubin formation. Presently, the effects in vivo and in vitro of Sn- and Zn protoporphyrins on HO-1 (HSP-32) and HO-2 at the protein and transcript levels were examined. Western blot analysis of HO-2 in testes microsomes of Sn protoporphyrin-treated rats revealed a dramatic disruption of the integrity of the HO-2 protein. Similar observations were made with the liver and adrenal HO-2 and the NADPH-cytochrome P-450 reductase of treated rats. Northern blot analysis, however, suggested unaltered tissue levels of HO-2 transcripts (approximately 1.9 and approximately 1.3 kb). The HO-1 protein integrity in organs of treated rats was less dramatically affected by the metalloporphyrin and an increase in its 1.8 kb mRNA level in the testes was detected. Zn-protoporphyrin also increased HO-1 mRNA level in the testes, but did not affect HO-2 protein integrity. In in vitro studies with purified HO-1 and HO-2, both Sn- and Zn-protoporphyrins were equally inhibitory to HO-1 activity; Sn-protoporphyrin, however, was by far more inhibitory to HO-2-dependent activity than to that of HO-1. Together, these findings and the fact that HO-2 under normal conditions is the predominant form of the enzyme in most organs suggest that loss of HO-2 protein integrity may to a significant degree account for suppression of bilirubin formation by Sn protoporphyrin. These in turn may reflect differences between HO-1 and HO-2, both at the transcriptional level with HO-2 being noninducible, and in structure/composition of the isozymes, with HO-2 being more labile. PMID- 1610898 TI - Molecular structure of the C beta catalytic subunit of rat cAMP-dependent protein kinase and differential expression of C alpha and C beta isoforms in rat tissues and cultured cells. AB - A full-length cDNA clone encoding the C beta catalytic subunit of cAMP-dependent protein kinase (PKA) was isolated from a rat brain cDNA library. A 1.1 kb cDNA containing the entire coding region encodes for a protein of 351 amino acids that shows more than 95% sequence homology to the C beta subunits in mouse, bovine and human. Northern blot analysis showed distinct patterns of C alpha and C beta mRNA expression in the brain and various peripheral tissues. The C alpha mRNA was widespread and highly expressed in brain, heart, adrenal gland, testis, lung, kidney, spleen and liver, whereas the C beta mRNA was unevenly expressed in the brain and adrenal gland and in much lesser amounts in other tissues. The C alpha mRNA was evenly distributed and highly expressed through various regions of the brain, while the C beta mRNA was expressed in lesser amounts and was unevenly distributed. In neuronal and glial cultured cells, C alpha mRNA was also predominantly expressed but C beta mRNA was undetectable. The differential distribution between the C subunit isoforms of PKA suggests that individual subunits are involved in specialized functions. PMID- 1610899 TI - Elevation of metallothionein gene expression associated with hepatic copper accumulation in Long-Evans Cinnamon mutant rat. AB - The mechanism of the metallothionein (MT) gene expression was investigated in a mutant rat, LEC, which exhibits an abnormal accumulation of copper in hepatocytes. The levels of MT mRNA were extremely high and correlated with the hepatic copper concentrations in LEC rat liver. Gel retardation assays in nuclear extracts from LEC rat liver showed an increase in the copper-dependent binding proteins, which bind to the metal responsive element (MRE) of the MT gene. These results suggest that the high intracellular copper accumulation results in the elevation of the MT gene expression through increasing a putative trans activating factor in LEC rat. PMID- 1610900 TI - A comparison of the flanking regions of the mouse cytotoxic cell proteinase genes. AB - T lymphocyte activation correlates with the transcriptional induction of a variety of genes that encode proteins that are believed to play a role in specific effector functions of the mature cells. Transcripts corresponding to members of the cytotoxic cell proteinase (CCP) family of genes accumulate with different kinetics depending upon the nature of the T cell stimulus. The profile of expression for each family member is unique. Sequences corresponding to the 5' and 3' flanking regions of each of the CCP genes were isolated and sequenced. A comparison of these sequences reveal regions of conservation that are consistent with the differential expression observed and indicate potential regulatory elements. PMID- 1610901 TI - Identification of six open reading frames from a region of the Azotobacter vinelandii genome likely involved in dihydrogen metabolism. AB - We reported earlier the identification of two Azotobacter vinelandii open reading frames (ORFs), ORF1 and ORF2, downstream from the hydrogenase structural genes (Chen, J.C. and Mortenson, L.E. (1992) Biochim. Biophys. Acta 1131, 122-124). Sequencing of 6008 base pairs of DNA immediately downstream from ORF2 revealed six additional ORFs (ORF3 through ORF8). All six ORFs are transcribed from the same DNA strand as that of the ORF1 and ORF2. Deduced amino acid sequences of ORF3 through ORF5, and those of ORF4, ORF5, ORF7 and ORF8 have strong homology with genes required for dihydrogen (H2) metabolism in Rhodobacter capsulatus and in Escherichia coli, respectively. ORF4, ORF5, ORF6 and ORF8 would encode for polypeptides containing one or more 'Cys-X-X-Cys' motifs. The predicted products of ORF5 and ORF6 each contain a histidine-rich region, and the product of ORF5 also includes a 'Cys-Thr-Val-Cys-Gly-Cys' region near its amino-terminus. Implications of these findings with respect to metal binding, transport and incorporation, to hydrogenase assembly and to H2 metabolism are discussed. PMID- 1610902 TI - Nucleotide sequence of the cynomolgus monkey apolipoprotein A-I gene and corresponding flanking regions. AB - The cynomolgus monkey (Macaca fascicularis) apolipoprotein A-I (apo A-I) gene and corresponding flanking regions have been isolated from a cynomolgus monkey genomic library and completely sequenced. Comparison with the human sequence shows a greater than 90% homology with the monkey sequence, overall. The monkey apo A-I structural gene (1856 bp) is representative of the general apolipoprotein gene structure and consists of four exons and three introns. Minor differences exist between the monkey and human structural gene sequence but do not result in significant changes. Sequences preceding the putative monkey apo A-I promoter are virtually identical to the human apo A-I enhancer region with an exact match to the three enhancer DNA binding sites. PMID- 1610903 TI - A novel isoform of rat hepatocyte nuclear factor 4 (HNF-4). AB - Based on the published nucleotide sequence for rat hepatocyte nuclear factor 4 (HNF-4; Sladek, F.M., Zhong, W., Lai, E. and Darnell, J.E., Jr. (1990) Genes Dev. 4, 2353-2365), we have cloned a cDNA by means of polymerase chain reaction amplification of reverse-transcribed RNA (RT-PCR). Our clone contained an extra segment of 30 bp, which was not found in the previously reported clone, in the coding region near the C-terminus. Further RT-PCR analysis demonstrated that both isoforms of HNF-4 mRNA, i.e., with or without the 30 nucleotide segment, occur in rat liver and kidney, presumably by differential splicing. PMID- 1610904 TI - Upstream region of a genomic gene for human mitochondrial transcription factor 1. AB - A genomic gene for human mitochondrial transcription factor 1 was cloned from a human genomic library and its 5' flanking region was sequenced. No typical TATA and three consensus sequences for potential Sp1 binding site were found in its 5' flanking region of 2 kilobase pairs. There were, at least, four common sequences among some nuclear genes for mitochondrial-related proteins. PMID- 1610905 TI - Human casein kinase II subunit alpha: sequence of a processed (pseudo)gene and its localization on chromosome 11. AB - A human 4.3 kb genomic DNA fragment, containing the information of a processed (pseudo)gene of casein kinase II subunit alpha (CKII alpha) was isolated and sequenced. The genomic CKII alpha sequence is 99% homologous to the CKII alpha cDNA, carries several nucleotide exchanges, a poly(A) stretch at its 3' end and is flanked at both ends by a 16 bp repeat. It has a promoter-like region including two TATA boxes and a CAAT box. Although translation of transcripts would be terminated by a stop codon after two third of the coding region, the resulting protein would still contain the catalytic domains. However, so far Northern blots with a 3' specific probe were negative. The 4.3 kb genomic fragment containing the processed CKII alpha (pseudo)gene was mapped by in situ hybridization to chromosome 11p15. PMID- 1610906 TI - Cloning and nucleotide sequences of two lipase genes from Candida cylindracea. AB - Two lipase-encoding genes (LIP1 and LIP2) have been isolated from a SacI genomic library of the yeast Candida cylindracea and their nucleotide sequences have been determined. Comparison with the sequence of a cDNA ruled out the presence of introns in the two genes. Both ORFs encode for mature proteins of 534 residues with putative signal peptides of 15 and 14 amino acids, respectively. When compared with other lipase sequences, the two C. cylindracea lipases showed homology only with the Geotrichum candidum lipase, whereas they shared a significant similarity with several esterases. PMID- 1610907 TI - Structure of Drosophila virilis glycerol-3-phosphate dehydrogenase gene and a comparison with the Drosophila melanogaster gene. AB - The complete glycerol-3-phosphate dehydrogenase gene of Drosophila virilis isolated by screening with alpha GPDHM cDNA of the adult fly was sequenced. The gene contains eight exons spread over a total of approximate 8 kb DNA. Its exon/intron organization is identical to that of D. melanogaster. A single transcription initiation site was determined by primer extension. The stop codons are located at the 3' end of each of the exons 6 to 8. TATA and CAAT boxes are present upstream of the transcriptional start site. Adult alpha GPDH protein is encoded by exons 1 to 6 and exon 8. Comparison of the sequence with that of D. melanogaster showed that the homology of the nucleotide sequence of the coding region is 85% and that the homology of the amino acid sequence is 98%. On the contrary, the non-coding region is quite different in length and nucleotide sequence. PMID- 1610908 TI - Isolation and characterization of cDNA clones encoding the skeletal and smooth muscle Xenopus laevis beta tropomyosin isoforms. AB - cDNAs clones corresponding to the skeletal and smooth muscle beta tropomyosins isoforms were isolated from a Xenopus laevis embryo cDNA library. Sequence analysis indicated that the two isoforms are coded by a single gene that uses two couples of alternative exons. The expression of the X. laevis beta tropomyosin gene closely resembles that of the mammalian gene but differs from the avian gene. PMID- 1610909 TI - Comparative studies on the extractability of collagen from aortas of stroke-prone spontaneously hypertensive and normotensive rats. AB - The molecular states of collagen in the aortas of age-matched stroke-prone spontaneously hypertensive (SHRSP) and normotensive Wistar Kyoto rats (WKY) were studied by analyzing its extractability under defined conditions. The monomeric and oligomeric collagen extractable with 0.5 M acetic acid/6 M urea from aortic homogenates of 9-month-old SHRSP and WKY comprised approx. 0.6 and 2.0%, respectively, of the total collagen. On incubation of the acetic acid/urea extracted residues with pepsin at 4 degrees C, the levels of the collagen alpha 1(I) and alpha 2(I) chains solubilized from the SHRSP residues were both less than 50% of those from the WKY residues. When the residues were incubated with pepsin at 15 or 25 degrees C, the differences became smaller. When the acetic acid/urea residues were hydrolyzed with cyanogen bromide, nearly identical peptide maps were obtained for SHRSP and WKY. The aortas from 2-month-old SHRSP and WKY contained much larger proportions of acid/urea-extractable collagen than those of the older rats (8.2 and 13% of the respective total collagen). The levels of the alpha 1(I) and alpha 2(I) chains solubilizable from the respective residues by pepsin at 4 degrees C were similar to each other. These results indicate that aortic collagen fibrils in SHRSP are stiffened more prominently than those in WKY. PMID- 1610910 TI - 31P-NMR spectroscopy of perifused rat hepatocytes immobilized in agarose threads: application to chemical-induced hepatotoxicity. AB - A system consisting of isolated rat hepatocytes immobilized in agarose threads continuously perifused with oxygenated Krebs-Henseleit (KH) solution has been found to maintain cell viability with excellent metabolic activity for more than 6 h. The hepatocytes were monitored by phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy at 4.7 Tesla, by measurement of oxygen consumption and by the leakage of lactate dehydrogenase (LD) and alanine aminotransferase (ALT). The data obtained were comparable to those found for an isolated perfused whole liver in vitro. The effects of allyl alcohol (AA), ethanol, and 4-acetaminophenol (AP) were examined. A solution of 225 microM AA perifused for 90 min caused the disappearance of the beta-phosphate resonance of adenosine triphosphate (ATP) in the 31P-NMR spectra, a 7-fold increase in LD leakage and a 70% reduction in oxygen consumption. Ethanol (1.0 M) perifused for 90 min reduced the beta-ATP signal intensity ratio by 20%, the phosphomonoester (PME) signal by 50% and inorganic phosphate (Pi) by 33% (P less than 0.05). AP (10 mM) caused only mild liver-cell damage. The results demonstrate that perifused immobilized hepatocytes can be used as a liver model to assess the effects of a wide range of chemicals and other xenobiotics by NMR spectroscopy. PMID- 1610911 TI - Variations in the relative amounts of biotin-containing enzymes present in both tumorigenic and non-tumorigenic hybrid cells and other cell lines. AB - The observation that radioactively labelled streptavidin binds to several biotin containing enzymes in mammalian cells has led to the finding that there is considerable variation in the proportion of these enzymes present (namely beta methyl crotonyl CoA; propionyl CoA; pyruvate and acetyl CoA, carboxylases). This is particularly striking when certain tumorigenic and non-tumorigenic hybrid cells are compared. It is found that there is a consistently higher proportion of pyruvate carboxylase in the tumorigenic hybrid cells. However, not all tumorigenic cell lines show this same characteristic and reasons for this are discussed. It is also shown that whilst the proportions of the four enzymes are apparently constant for a given cell type, there is a substantial degree of clonal variation and this is particularly so in tumorigenic cells in vitro. However, the more tumorigenic cells in a given population do show a higher proportion of pyruvate carboxylase. Also a range of cells derived from lymphoid tissue has been compared with normal human lymphocytes and considerable differences are again observed. The significance of these findings is considered in relation to other phenotypic properties of hybrid cells. PMID- 1610912 TI - Characterization of ATP-diphosphohydrolase activities in the intima and media of the bovine aorta: evidence for a regulatory role in platelet activation in vitro. AB - The inner layer of the aorta contains the enzyme ATP diphosphohydrolase (ATPDase: EC 3.6.1.5) which catalyzes the sequential phosphorolysis of ATP----ADP----AMP. Two zones of the inner layer, the intima and media, were separated and both were shown to contain ATPDase activity of similar specific activity (0.08 and 0.10 U/mg protein, respectively). However, the media exhibited about 100-times more enzyme activity than the intima. Both preparations were virtually identical with respect to pH optima (7.5), migration patterns after electrophoresis under non denaturing conditions, relative rates of ATP and ADP hydrolysis and potency to inhibit ADP-induced platelet aggregation in both human platelet-rich plasma and whole blood. The IC50 values for ADP (2 microM)-induced aggregation were 6.8 and 12.9 mU/ml in platelet-rich plasma and whole blood, respectively. Addition of ATPDase to platelets pre-aggregated with ADP resulted in a dose-dependent disaggregation in platelet-rich plasma (IC50 4.9 mU/ml), but not in whole blood. When both ATPDase (5.6-58.7 mU/ml) and ATP (0.5-10 microM) were added to platelet rich plasma, there was an immediate dose-dependent aggregation of platelets followed by a slowly developing disaggregation. These data show that ATPDase is present in both the intima and media layers of bovine aorta and suggest a dual role for this enzyme in platelet activation. By converting ATP released from damaged cells into ADP, the enzyme could facilitate platelet aggregation at the site of vascular injury, whereas the subsequent conversion of ADP to AMP could inhibit or reverse platelet aggregation. The consequence of these activities would be to control the growth of a platelet thrombus. PMID- 1610913 TI - Phospholipase D signaling in ischemic heart. AB - Phospholipase D (PLD) activity was found to be present in the membrane fraction of rat myocardial cells by in vitro assays (36.7 +/- 4.1 nmol/mg protein per h against 1-palmitoyl-2-arachidonoyl- phosphatidylcholine) and demonstrated in intact cells by the specific transphosphatidylation reaction (in the presence of 0.02% ethanol) quantitated using n-[1-14C]butanol (201.16 +/- 7.1 pmol/min per g dry weight in the whole heart). Both methods showed a significant increase in PLD activity (by 62 and 44%, respectively) in hearts subjected to reversible (30 min) global normothermic ischemia followed by reperfusion (30 min). In hearts prelabeled with [1-14C]arachidonic acid, ischemia/reperfusion induced a significant increase in the amount of radiolabel incorporated into phosphatidic acid (PtdOH) (by 49.6%) and diacylglycerol (DG) (by 259%). DG kinase inhibition by 100 microM dioctanoylethylene glycol did not affect the ischemia/reperfusion DG and PtdOH levels while PtdOH phosphohydrolase inhibition with 40 microM propranolol produced a further increase in PtdOH (to 2.36-fold the baseline level) and a reduction in DG (to only 145% over the baseline levels). Put together, all these results suggest an activation of PLD during myocardial ischemia/reperfusion generating intracellular PtdOH, part of which is converted by PtdOH phosphohydrolase to DG. We further investigated the possible pathophysiological significance of the observed PLD activation. Stimulation of PLD with sodium oleate (20 microM) induced a significant improvement of functional recovery of ischemic hearts during reperfusion (as monitored by coronary flow and left intraventricular pressure measurements) and an attenuation of cellular injury as expressed by lactate dehydrogenase and creatine kinase release in the coronary effluent during reperfusion. These results suggest a PLD mediated signaling in the ischemic heart which may benefit functional recovery during reperfusion. PMID- 1610914 TI - Substratum acidification by murine B16F10 melanoma cultures. AB - Murine B16F10 melanoma cells, adherent to thin films of crosslinked, fluorescein labeled collagen I, and covered by a thin layer of 0.7% agarose, exhibit a decrease in fluorescence emission in the substratum region immediately beneath adherent cells. The relative diminution in fluorescence intensity is dependent on excitation wavelength and is observed following excitation at 490 nm, but is not observed following excitation at 452 nm. The decrease in fluorescence emission is not due to quenching or concentration effects and is attributed to the decrease in extracellular pH in the substratum region. Fluorescence measurements of (I490/I452) within these substratum regions, correlate with an average extracellular pH of 6.4 +/- 0.2 which drops to pH less than 5 after 5 h. It is suggested that this region is sufficiently acidic to activate secreted or cell surface acid proteinase enzymes and that the activity of these enzymes may be important in invasiveness by this cell-line. PMID- 1610915 TI - Identification of Hb Hamilton or beta 11(A8)Val----Ile gene by the polymerase chain reaction amplification technique. AB - Amplification of the beta-globin gene by the PCR technique, followed by the enzymatic digestion of the DNA fragment obtained, was used to easily identify the human beta-globin variant Hb Hamilton which is characterized by the valine to isoleucine substitution at position 11. The result revealed the predicted G to A transition at codon 11 which abolishes a MaeIII restriction site. This mutation, which is rather common among Sardinians, is at the level of one of the five CpG dinucleotides of the beta-globin gene. PMID- 1610916 TI - Glucuronidation of 3'-azido-3'-deoxythymidine in human liver microsomes: enzyme inhibition by drugs and steroid hormones. AB - The molecular form of UDP-glucuronosyltransferase involved in the catalysis of 3' azido-3'-deoxythymidine (AZT)-5'-O-glucuronide was characterized in human liver microsomes. The specific activity (1.3 nmol/min per mg protein) in transplantable liver was more than 2-times higher than in post-mortem fragments. Liver microsomes from patients suffering Crigler-Najjar syndrome, who are genetically deficient in bilirubin UDP-glucuronosyltransferase, could also glucuronidate AZT to a similar extent, thus indicating that this protein was not involved in that process. A genetically engineered V79 cell line stably expressing a cDNA which encodes a human isozyme active towards 1-naphthol was unable to glucuronidate AZT. Clinically used drugs, most of them being glucuronidated, were tested as potential inhibitors of the glucuronidation of AZT in human liver microsomes. The drugs chemically related to 2-phenylpropionic acid, naproxen and flurbiprofen, and the steroid compounds testosterone, estrone and ethynylestradiol strongly inhibited AZT glucuronidation. Codeine and morphine also decreased the reaction rate although to a lower extent. Except estrone which elicited a partial competitive inhibition, ethynylestradiol, flurbiprofen naproxen and testosterone could competitively inhibit AZT glucuronidation with an apparent Ki of 38, 50, 172 and 250 microM, respectively. The results suggest that these drugs were substrates of the same isozyme(s) involved in AZT glucuronidation. Probenecid was a weak inhibitor of the reaction (Ki 900 microM), only when non-disrupted microsomes were used. This drug may compete with the anion carrier system involved in the microsomal uptake of UDP-glucuronic acid. PMID- 1610917 TI - Alterations in erythrocyte membrane lipid composition and fluidity in primary lipoprotein lipase deficiency. AB - Lipid composition of plasma lipoproteins and erythrocyte ghost membranes has been studied in 16 healthy normolipidaemic subjects and in 16 patients affected by primary lipoprotein lipase deficiency, resulting in severe chylomicronaemia and in cholesterol-depleted low-density lipoproteins and high-density lipoproteins. A significant decrease in membrane cholesterol/phospholipid ratio was observed in lipoprotein lipase deficient patients compared to controls (3.27 +/- 0.33 vs. 3.95 +/- 0.50, mean +/- S.D.; P less than 0.0001). There was also an increase in the erythrocyte membrane phosphatidylcholine/sphingomyelin ratio in lipoprotein lipase deficient patients compared to controls (1.53 +/- 0.10 vs. 1.05 +/- 0.13; P less than 0.0001) due to a concurrent increase in phosphatidylcholine and decrease in sphingomyelin relative concentrations in these patients. Erythrocyte ghost membrane fluidity was determined by fluorescence anisotropy and found to be higher in membranes from lipoprotein lipase deficient patients. This increase in membrane fluidity can be attributed in part to changes in membrane cholesterol and phospholipid concentrations in response to abnormal plasma lipoprotein composition. PMID- 1610918 TI - Chloride transport in control and cystic fibrosis human skin fibroblast membrane vesicles. AB - Plasma membrane vesicles were isolated from either cystic fibrosis (CF) or non-CF cultured fibroblasts derived from skin biopsies of either foetus, child or adolescent human donors. The total membrane yield was essentially identical for either CF or control membranes. By using a rapid filtration technique, 36Cl uptake by these vesicles was quantitated in the absence and presence of alkali metal ion-, electrical- and/or pH gradients. In the absence of a pH gradient (pHout = pHin = 7.5), Cl uptake took place downhill in both cases. Either cis K+, cis Na+ or an equimolar mixture of cis Na+ plus K+ caused Cl uptake activation. In the presence of an alkaline-inside pH gradient (pHout/pHin = 5.5/7.5), Cl uptake exhibited an apparent overshoot independently of the presence or absence of any metal-ion gradient. The observed potassium-, sodium- and proton-dependent Cl influx rates were all unaffected by voltage clamping, indicating the existence in these vesicles of electroneutral symport systems of the type Cl-/H+, Cl-/K+ and/or Cl-/Na+; but not 2 Cl-/Na+/K+. In the presence of an inward-directed K+ gradient, valinomycin further increased Cl uptake, both in the presence and in the absence of a pH gradient, indicating the presence of a rheogenic Cl uniport. In absolute quantitative terms, the two different modes (rheogenic and electroneutral) of Cl transport evinced in these vesicles were about 45% lower in CF than in control skin fibroblasts. However, qualitatively, there was no difference between normal and CF cells. The evidence obtained indicates that the CF defect, which is expressed in fibroblast plasma membranes, does not affect specifically either the rheogenic or the electroneutral Cl transport systems. Rather, the CF cells appear to give a smaller yield of closed, functional vesicles, reflected by a significantly smaller apparent intravesicular volume. Because it also affects the transport of D-glucose and L-alanine, this anomaly could be the consequence of a generalized membrane defect characterizing CF fibroblasts. PMID- 1610919 TI - Exposure of HIV-infected cells to phospholipid leads to membrane alterations and selective growth retardation. AB - The effect of exogenous phosphatidylcholine on structure and function of plasma membranes from HIV-1-producing cells and from their non-infected counterparts was determined. The membrane protein composition was not affected by phospholipid treatment. Membrane fluidity and Ca(2+)-permeability were increased in virus producing cells and in control cells after lipid treatment. The triacylglycerol content of the plasma membranes was increased in virus-producing cells after lipid treatment, whereas the content of phospholipid and cholesterol was not changed. The increased triacylglycerol content was in accordance with a relatively higher rate of [14C]oleic acid incorporation into triacylglycerols of the virus-producing cells after lipid treatment as shown by metabolic labeling. The results suggest that a latent cytopathic effect of HIV-infection becomes manifest if the cells are exposed to exogenous phospholipid and this may open a way to preferentially eliminate HIV-producing cells. PMID- 1610920 TI - Modifications in platelet membrane transport functions in insulin-dependent diabetes mellitus and in gestational diabetes. AB - The pathogenesis of plasma membrane alterations present in diabetes mellitus is unclear. To add new insights to the question, platelet membrane properties were evaluated in 16 women presenting impaired glucose tolerance at the 28-29th week of gestation (GDM) and in 8 women with insulin-dependent diabetes mellitus (IDDM). 15 healthy pregnant women (HPW) and 21 healthy non-pregnant (HNPW) women were the control group for GDM and IDDM, respectively. Pregnancy (HPW vs. HNPW) provoked an increase in Ca(2+)-ATPase activity and a decrease in membrane fluidity; in contrast, Na+/K(+)-ATPase, intracellular free Ca2+ concentrations, membrane cholesterol and phospholipid content did not vary. Both GDM and IDDM showed lower Na+/K(+)-ATPase activity and higher Ca2+ concentration, compared to HPW and HNPW, respectively, whereas Ca(2+)-ATPase activity was higher only in IDDM; furthermore, membrane fluidity was lower in GDM and higher in IDDM. Finally, GDM showed higher membrane cholesterol content. Both GDM and IDDM showed a very good metabolic control so that variations reported cannot be due to hyperglycemia; it is tempting to suggest that membrane variations are present before the clinical metabolic alteration. Furthermore, both GDM and IDDM were on insulin therapy, therefore: (i) insulin may be the pathogenetic factor of higher intracellular free Ca2+ concentrations and lower Na+/K(+)-ATPase activity since they both varied accordingly in GDM and IDDM, but not of (ii) changes in Ca(2+) ATPase, membrane fluidity and cholesterol content which did not vary accordingly in GDM and IDDM. PMID- 1610922 TI - Alteration in molecular structure which results in disease: the Met-30 variant of human plasma transthyretin. AB - The structure of a variant transthyretin has been determined by X-ray crystallography at 2.3 A resolution in order to investigate those changes which lead to amyloid formation. This variant transthyretin, in which the internal valyl residue at position 30 is replaced by methionyl, is associated with the most common form of familial amyloidotic polyneuropathy (FAP). Comparison to the known structure of the normal transthyretin tetramer shows that the bulkier methionine residue 30 which lies between the nearly orthogonal beta sheets of the dimer, results in the sheets being displaced an average of 0.4 A. The internal structure of the sheets and of the monomer-monomer interface is maintained. Such global changes may affect the metabolic properties and the tendency towards polymerization of the mutant protein. These findings may form a basis for understanding other amyloid-deposition diseases. PMID- 1610921 TI - Hyaluronate synthesized by cultured skin fibroblasts derived from patients with Werner's syndrome. AB - Hyaluronate in cultured skin fibroblasts derived from patients with Werner's syndrome, who excrete large amounts of urinary hyaluronate, was investigated. The amount of hyaluronate secreted into the medium by Werner's fibroblasts was 2-3 times that of normal fibroblasts, whereas no difference in enzyme activities related to the degradation of hyaluronate was found. Werner's fibroblasts were then cultured in the presence of [3H]glucosamine, and the amount of [3H]hyaluronate and its chain lengths in the medium and matrix (trypsinate) fractions were compared with those of normal cells. No significant difference in the chain length of hyaluronate was observed between normal and Werner's fibroblasts. On the other hand, a significant increase of hyaluronate was found in the matrix fraction of Werner's fibroblasts when the cells reached confluency. In addition, a hyaluronate of small chain length was found in the matrix fraction of Werner's fibroblasts, although this was absent from that of normal cells. It was concluded that the constituents of the extracellular matrix of Werner's fibroblasts differed from those of normal cells, characterized by the presence of a large amount of hyaluronate and a relatively small hyaluronate chain. PMID- 1610923 TI - Expression of different isoenzymes of adenylate deaminase in cultured human muscle cells. Relation to myoadenylate deaminase deficiency. AB - Adenylate deaminase activity was determined in cultured muscle cells of different maturation grades and muscle biopsies from normal subjects and four patients with a primary myoadenylate deaminase (MAD) deficiency. Adenylate deaminase activity was much lower in cultured human muscle cells than in normal muscle. The activity increased with maturation. The ratio of activities measured at 5 and 2 mM AMP decreased in the order: immature muscle cells greater than more mature muscle cells greater than muscle. Adenylate deaminase activity was detectable in muscle cell cultures of MAD-deficient patients. However, both at 2 and 5 mM AMP this activity was significantly lower than in cultured cells with the same high maturation grade obtained from control subjects, whereas the ratio between the activities at 5 and 2 mM AMP was higher. The observations indicate that transition from a fetal to an adult muscle isoenzyme of adenylate deaminase takes place in human cultured muscle cells during maturation. In cultures obtained from MAD-deficient patients this transition does not occur and only the fetal isoenzyme is present. PMID- 1610925 TI - [Image quality parameters characterizing radiologic imaging systems]. AB - The image quality of imaging systems can be characterized by a number of parameters, such as the easy to appreciate concepts of resolution or contrast or such precisely defined and measurable characteristics as the modulation transfer function or the noise spectrum. The meaning of these qualities and their interrelation are discussed. From these parameters, we can derive one of the most important characteristics for the description of the physical image quality = the signal-to-noise ratio. PMID- 1610924 TI - Proteoglycans synthesized by the hepatic granulomas isolated from schistosome infected mice and by the granuloma-derived connective tissue cell lines. AB - Proteoglycans synthesized in vitro by periovular granulomas isolated from livers of schistosome-infected mice were compared with those produced by granuloma derived cell lines: the primary cell line GR and the permanent cell line GRX. Proteoglycans were metabolically labelled with 35S-sulfate and extracted with 4 M guanidine-HCl containing 2.0% Triton X-100, in the presence of proteinase inhibitors. The radiolabelled proteoglycans were purified and characterized by anion-exchange, gel-filtration and affinity-column chromatography. Heparan sulfate proteoglycans (HS-PGs) and chondroitin sulfate/dermatan sulfate containing proteoglycans (CS/DS-PGs) were detected in both the culture medium and the cell-associated fractions obtained from GR cells. More than 90% of the cell associated HS-PG from these cells contained a hydrophobic portion, as evidenced by their ability to bind to octyl-Sepharose. In contrast, among the secreted proteoglycans, it was the CS/DS-PG and not the HS-PG that bound to this resin. The major fractions of cell-associated and secreted proteoglycans from GRX cells were HS-PGs. Similar to HS-PGs from GR cells, 50% of the cell-associated HS-PG bound to octyl-Sepharose, while only 20% of secreted proteoglycans (HS-PGs) bound to this resin. The proteoglycans purified from the whole granuloma were composed mainly of DS-PG, of a size and hydrophobicity similar to the CS/DS-PG from GR cells. Possible correlations among the structure, secretion, distribution and function of proteoglycans in granulomatous reactions are discussed. PMID- 1610926 TI - [Dose requirements for projection techniques in x-ray diagnosis]. AB - The dose required in x-ray diagnosis depends upon the demands made on a diagnostically optimal x-ray film or in fluoroscopy, and upon the technical quality of the equipment. The actual dose requirement, derived from field studies, is juxtaposed on the basis of representative examples with the maximum permissible dose requirement in accordance with the prescribed minimum sensitivity values of the x-ray film. The ideal dose requirement has been stated by Cohen et al. (1981) by a formula basing on parallel beam, maximum quantum yield and Bucky grid effect depending on the signal to noise ratio and object contrast. This was checked by means of contrast detail diagrams measured at the hole phantom, and was additionally compared with measurement results obtained by Wust et al. (1989) with acrylic glass phantoms. The optimal dose requirement is obtained by the maximum technically possible approach to the ideal requirement level. Examples are given, besides for x-ray equipment with Gd2 O2 S screen film systems for grid screen mammography, and new thoracic examination systems for mass screenings. Finally, a few values concerning the dose requirement or the analogous time required for fluorescent screening in angiography and interventional radiology, are stated, as well as for dentistry and paediatric x ray diagnostics. PMID- 1610927 TI - [Anterior cruciate ligament rupture: MT versus arthroscopy]. AB - Because of suspected rupture of the anterior cruciate ligament sixteen acute traumatised patients were investigated by MR and arthroscopy. The MR diagnosis of a lesion of the anterior cruciate ligament proved to be correct by arthroscopy in fifteen of sixteen cases. Diagnostic criteria for lesions of the anterior cruciate ligament were: Increased signal intensity in T1- and T2 weighted images, increased volume and discontinuity of ligamentous structures. Additional MR findings of meniscal tears were correct in three of four cases laterally and in four of four cases medially. Femoral cartilage lesion were correctly identified by MR in three cases. MR normal findings proved to be correct by arthroscopy in another five cases. PMID- 1610928 TI - [The diabetic foot--current possibilities of vascular reconstruction]. AB - Arterial vascular disease in diabetic patients includes both microangiopathy and macroangiopathy. Macroangiopathy, i.e. stenoses of occlusions of the ilio-femoro popliteal arteries and crural arteries, can be treated by surgical vascular reconstructions and radiological procedures such as recanalisation via catheter and CT-guided lumbar sympathetic trunk, neurolysis. In this paper the different therapeutic techniques are presented in respect of indications and results particularly in the diabetic patients. PMID- 1610929 TI - [Tolerability of nonionic contrast media--results of a multicenter double blind study]. AB - The aim of the randomized multicentre double-blind study was to establish whether nonionic contrast media differ in tolerability. The controlled comparison was conducted at 4 centres on a total of 798 patients with indication for i.v. DSA and computed tomography. The nonionic contrast media Iopamidol and Iopromide with an iodine content of 300 mg/ml each were studied. The osmolality of both contrast media is virtually identical. Both groups of patients were largely homogeneous in terms of demographic data and case history. The history of allergies was positive in 32.4% of the Iopamidol group and in 32.3% of the Iopromide group. The arithmetic mean of the doses administered to each patients was 148.3 and 149.3 ml, respectively. At all 4 centres there was a higher incidence of adverse events with Iopromide than with Iopamidol. The main differences with regard to pseudo allergic reactions was the incidence of urticarial reactions, pruritus, nausea, vomiting and coughing. 89 of the 399 patients (22.3%) receiving Iopamidol and 120 of the 399 patients (30.1%) receiving Iopromide experienced pseudo-allergic reactions. The difference between both contrast media is statistically significant (p less than 0.05). There is a 95% certainty that less pseudo allergic reactions will occur after an Iopamidol injection than after Iopromide. Possible explanations for the differences in tolerability between the two nonionic contrast media with identical osmolality are discussed. PMID- 1610931 TI - [An atypical site of a solitary eosinophilic granuloma in the distal humerus]. AB - The case of a ten-year old girl, presenting with pain and restricted movement of the left arm is reviewed. X-rays and bone scan suggested an Ewing's sarcoma of the left humerus, so that the child was referred to surgery. Surprisingly, the histological examination of the surgical specimen revealed a solitary eosinophilic granuloma of the bone. PMID- 1610930 TI - [Genetic disposition of atherosclerosis? Case report of a monozygotic pair of twins]. AB - The case of a 64-year old pair of monozygotic male twins with atherosclerotic disease of the iliaca arteries is described and the related literature dealing with the genetics of atherosclerosis is reviewed. Both patients had corresponding clinical history and physical findings and showed an almost identically localised and a high degree of stenosis of the right iliac artery of similar appearance. In both cases percutaneous transluminal angioplasty (PTA) was performed prior to placement of Plamaz stents. The well-known risk factors of atherosclerosis are hypertension, hypercholesterolaemia, cigarette smoking, diabetes mellitus, obesity, physical inactivity, and psychosocial influences. However, a number of atherosclerotic lesions cannot be accounted for solely on the basis of current knowledge of these risk factors. The reported case produces evidence of genetic factors as contributing components in the pathogenesis of established atherosclerotic disease. PMID- 1610932 TI - [Magnetic resonance tomographic characteristics and a follow-up observation in a case of cystic lymphangiomas in the left lower extremity, the retroperitoneum and the mediastinum]. AB - Lymphangiomas are rare benign tumours of the lymphatic system and are mostly manifested in the ENT region. The authors describe a rare localisation of this disease originating in the left lower extremity and extending into the retroperitoneum and mediastinum in a 16-year old female patient. MR enabled the diagnosis and the exact determination of the extent. MR follow-up showed 1 1/2 years after the diagnosis that the lymphangiomas and the lymphangioma in the left thigh had reduced and that the proliferation of lymphangioma in the retroperitoneum and mediastinum had stagnated. PMID- 1610933 TI - [Pigmented villonodular synovitis of the shoulder joint in childhood]. AB - A case of a 5-year-old boy with a pigmented villonodular synovitis of the shoulder is described in this article for the first time. The clinical features, preoperative diagnostic imaging including MRI and treatment were explained and compared with the literature. PMID- 1610934 TI - The role of proteinases in muscle growth and meat quality, special OECD workshop. Nottingham, UK, April 1991. PMID- 1610935 TI - The calpain-calpastatin system in mammalian cells: properties and possible functions. AB - All mammalian cells contain a calcium-dependent proteolytic system, composed by a proteinase, calpain, and an inhibitor, calpastatin. In some cell types an activator protein has also been identified. Moreover, two calpain isoforms, distinguishable on the basis of a different calcium requirement, can be present in a single cell. Both calpain forms are heterodimers composed of a heavy subunit (80 kDa) that contains the catalytic site and a smaller (regulatory?) subunit (30 kDa). Calpain I expresses full activity at 10-50 microM Ca2+, whereas calpain II requires calcium concentrations in the millimolar range. The removal by autoproteolysis of a fragment from the N-terminus of both calpain subunits generates a proteinase form that can express catalytic activity at concentrations of Ca2+ close to the physiological range. This process is significantly accelerated in the presence of cell membranes or phospholipid vesicles. Calpastatin, the specific inhibitor of calpain, prevents activation and the expression of catalytic activity of calpain. It is in itself a substrate of the proteinase and undergoes a degradation process which correlates with the general mechanism of regulation of the intracellular proteolytic system. The natural calpain activator specifically acts on calpain II isoform, by reducing the Ca2+ required for the autoproteolytic activation process. Based on the general properties of the calpain-calpastatin system and on the substrate specificity, its role in the expression of specific cell functions can be postulated. PMID- 1610936 TI - Role of the calpain system in muscle growth. AB - Muscle protein degradation has an important role in rate of muscle growth. It has been difficult to develop procedures for measuring rate of muscle protein degradation in living animals, and most studies have used in vitro systems and muscle strips to determine rate of protein degradation. The relationship between results obtained by using muscle strips and rate of muscle protein turnover in living animals is unclear because these strips are in negative nitrogen balance and often develop hypoxic cores. Also, rate of protein degradation is usually estimated by release of labeled amino acids, which reflects an average rate of degradation of all cellular proteins and does not distinguish between rates of degradation of different groups of proteins such as the sarcoplasmic and the myofibrillar proteins in muscle. A number of studies have suggested that the calpain system initiates turnover of myofibrillar proteins, which are the major group of proteins in striated muscle, by making specific cleavages that release thick and thin filaments from the surface of the myofibril and large polypeptide fragments from some of the other myofibrillar proteins. The calpains do not degrade myofibrillar proteins to small peptides or to amino acids, and they cause no bulk degradation of sarcoplasmic proteins. Hence, the calpains are not directly responsible for release of amino acids during muscle protein turnover. Activity of the calpains in living cells is regulated by calpastatin and Ca2+, but the nature of this regulation is still unclear. PMID- 1610937 TI - The role of Ca(2+)-dependent proteases (calpains) in post mortem proteolysis and meat tenderness. AB - This manuscript summarizes research results from our laboratory regarding the role of endogenous proteases in post mortem proteolysis resulting in meat tenderization. Proteolysis of key myofibrillar proteins is the principal reason for ultrastructural changes in skeletal muscle associated with meat tenderization. Proteases should have the following characteristics to be considered as possible candidates for bringing about post mortem changes: i) to be located within skeletal muscle cells; ii) to have access to the substrate ie, myofibrils); and iii) to be able to hydrolyze the same proteins that are degraded during post mortem storage. Of the proteases located within skeletal muscle cells and thus far characterized, only calpains have all of the above characteristics. Numerous experiments conducted in our laboratory have indicated that the calcium dependent proteolytic system (calpains) is responsible for post mortem proteolysis. Some of this evidence includes: 1) incubation of muscle slices with buffer containing Ca2+ accelerates post mortem proteolysis; 2) incubation of muscle slices with Ca2+ chelators inhibits post mortem proteolysis; 3) infusion or injection of carcasses with a solution of calcium chloride accelerates post mortem proteolysis and the tenderization process such that post mortem storage beyond 24 h to ensure meat tenderness is no longer necessary; 4) infusion of carcasses with zinc chloride, a potent inhibitor of calpains, blocks post mortem proteolysis and the tenderization process; and 5) feeding a beta-adrenergic agonist to lambs results in a reduction of the proteolytic capacity of the calpain system, which leads to a decreased rate of post mortem proteolysis and produces tough meat.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610938 TI - Non-enzymatic weakening of myofibrillar structures during conditioning of meat: calcium ions at 0.1 mM and their effect on meat tenderization. AB - The tenderness of meat is set by the properties of connective tissue and myofibrils. Skeletal muscle connective tissues become firm with chronological aging concomitantly with the increase in intermolecular non-reducing cross-links of collagen, and this process toughens meat, however, connective tissues hardly change during conditioning of meat. Therefore, the tenderization of meat during post mortem aging, or to put it more precisely, during post rigor aging, stems for the most part from changes in myofibril structures. My research derives its origin on findings of two kinds of post mortem changes in myofibril structures; i) fragmentation of myofibrils; and ii) restoration of rigor-shortened sarcomeres. These results were published in 1967 [1], and were, thereafter proved by many workers to be closely related to meat tenderization. I report in this paper the essential molecular mechanisms of these phenomena, and of structural changes in connectin or titin filaments. All of them are non-enzymatically induced by 0.1 mM calcium ion, which is the ultimate concentration of sarcoplasmic calcium ion in post mortem muscles. PMID- 1610939 TI - The effect of electrical stimulation on beef tenderness, protease activity and myofibrillar protein fragmentation. AB - From six one-year-old White red bulls, one randomly assigned carcass half was subjected to high voltage electrical stimulation (HVES) at 1 h post morten (pm). Longissimus dorsi (LD) steaks from control (C) and stimulated sides (ES) were removed at 24 h pm, stored at 4 degrees C and sampled at 1, 6, 8 and 12 days pm. HVES caused an immediate fall of pH with about 0.5 units (P less than 0.01), and an increase in temperature of about 1 degree C (P less than 0.05). HVES lowered LD shear force values (P less than 0.05), both at 1 and 8 days pm. Sarcomere length was not affected by stimulation, but cooking losses were increased in ES. Semi-quantitative SDS-PAGE, using BSA as internal standard showed the rate of degradation of several myofibrillar proteins to be increased by HVES. Levels of 43-kDa peptide increased upon ageing and were higher in ES (P less than 0.001). The level of 30-kDa peptide increases strongly in the early ageing period and faster in ES. It is striking that 1 h pm ES contain more 30 kDa (P less than 0.05), suggesting activation of calpain 1. The increase upon ageing in levels of 34- and 35-kDa peptides, often considered as the tropomyosins, suggests that these compounds are myofibrillar degradation products. Troponin-T (TNT) was degraded very fast in the early ageing period. The degradation rate was increased by HVES (P less than 0.005) and related to rate of tenderization (r = 0.90).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610941 TI - Long-term variability of heart rate increases with successful closure of patent ductus arteriosus in preterm infants. AB - Long-term variability (LTV) of heart rate was calculated continuously by a microprocessor in 25 preterm infants undergoing indomethacin treatment for closure of patent ductus arteriosus (PDA), in 24 preterm infants without signs of PDA, and in 10 neonates treated with prostaglandin E1 for cyanotic heart malformation. In infants with patent ductus arteriosus, LTV was lower than in controls. Following indomethacin, LTV increased most markedly (from 1.5 to 3.2; p less than 0.01) in infants with improved ventilation. The increase was less marked (from 1.8 to 2.5; p less than 0.05) in infants whose degree of respiratory failure did not change. LTV remained largely unchanged in infants who deteriorated. In 9 out of the 10 neonates treated with prostaglandin E1, LTV increased. We conclude that LTV corresponds to brain stem oxygenation and may be a useful tool to monitor treatment of PDA. PMID- 1610940 TI - Activities of pork muscle proteases in model cured meat systems. AB - The effect of curing agents (salt, nitrate, ascorbic acid and glucose) and processing parameters (pH, water activity and drying and cooking temperatures) on pork muscle cathepsins B, D, H and L as well as leucyl, arginyl and tyrosyl hydrolysing activities is reported. Salt (60 g/l) showed a powerful inhibitory effect, especially on cathepsin D and aminopeptidase activities where less than 13% of the original activity was recovered. Cathepsin H was also affected (38% of the original activity) while cathepsins B and B+L recovered 72.5 and 63.0%, respectively. Nitrate (0.2-0.25 g/l) and ascorbic acid (0.2-0.4 g/l) did not significantly affect the enzyme activities. On the other hand, 0.5-2 g/l of glucose activated both cathepsins B and D with an increase of 39.5 and 28.5% and also leucyl and arginyl hydrolysing activities which were 75.0 and 24.0%, respectively. No aminopeptidase activity was detected when assayed in 100 mM sodium citrate buffer, pH 5.1. Cathepsin H was also very affected at that pH and only 12.0% of activity was recovered. A decrease in water activity, especially below 0.84, also affected the enzyme activities which were found below 50%. Temperatures in the usual range of the drying process (22 and 30 degrees C) gave substantial enzyme activities (around 40-50 and 80%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610942 TI - Serum levels of immunoreactive inhibin, FSH, and LH in human infants at preterm and term birth. AB - Serum levels of immunoreactive inhibin, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were determined in 112 fetal cord blood samples obtained at birth between 26 and 40 weeks of gestation. High levels of inhibin immunoreactivity were detected in all samples. Between the gestational age of 26 and 28 weeks, the levels (mean +/- SE) were higher (p less than 0.05) in male (21.6 +/- 1.0 U/ml; n = 12) than in female (12.8 +/- 0.2 U/ml; n = 12) fetuses. With ongoing gestation, the serum inhibin immunoreactivity decreased and was found to be similar in male (12.1 +/- 0.3 U/ml; n = 13) and female (9.1 +/- 0.7 U/ml; n = 8) fetuses at term. Serum FSH and LH levels were elevated at the beginning of the 3rd trimester of pregnancy and decreased with ongoing gestation to undetectable values at term birth. Between 26 and 32 weeks of gestation, the FSH levels were higher in females (p less than 0.02), whereas the LH levels were higher in males (p less than 0.01). These observations suggest that in the human fetus the pituitary-gonadal axis is active and presents sexual dimorphism; both characteristics are pronounced early during the 3rd trimester of gestation and decrease towards term. PMID- 1610943 TI - Two-color flow cytometric analysis of natural killer and cytotoxic T-lymphocyte subsets in peripheral blood of normal human neonates. AB - It has been demonstrated that normal human newborns had significantly lower percentages of CD8+, CD11b+, CD16+ and CD56+, compared to adults, while no differences had been noted for the absolute numbers of these cells. Both the proportions and absolute numbers of CD57+ lymphocytes and cytotoxic T cells that mediate non-MHC-restricted cytotoxicity (CD3+CD56+) were markedly reduced in neonatal blood. Mean proportions but not absolute numbers of precursors and effectors of allocytotoxic T cells (CD8+CD11b-) significantly decreased in human neonates. Dual-labeling experiments demonstrated that newborns' natural killer cells had a phenotype different from that of adults. In newborns, there were much higher levels of CD11b+ cells, much lower levels of CD57+ cells and similar levels of CD8+ lymphocytes among CD16+ lymphocytes. It seems that a phenotype immaturity of natural killer cells may contribute to the diminished cytotoxic potential of neonatal lymphocytes. PMID- 1610945 TI - Polycythemia of the preterm and full-term newborn infant: relationship between hematocrit and gestational age, total blood solutes, reticulocyte count, and blood pH. AB - The umbilical venous hematocrit at birth (Hct 1) and the peripheral venous hematocrit at 2 h of life (Hct 2) were determined in 78 healthy full-term and 14 healthy preterm newborn infants. Hct 1 was 51.6 +/- 4.1% in full-term infants and 50.8 +/- 4% in preterm infants. Hct 2 was 60.9 +/- 2 and 58.6 +/- 6.1% in full term and preterm infants, respectively. Significant differences between Hct 1 and Hct 2 were found in both groups of infants (p less than 0.01). The blood viscosity increased significantly in both groups from birth to 2 h of life. Neonatal polycythemia (Hct higher than 70% at 2 h of life) was detected in only 3 full-term infants (3.8%). They received partial exchange transfusion. There was a positive linear correlation of Hct 1 with Hct 2 in full-term newborns (r = 0.71, p less than 0.001) and preterm infants (r = 0.57, p less than 0.02). No infants with Hct 1 equal to or below 50% had Hct 2 higher than 65%. None with Hct 1 between 51 and 54% had Hct 2 higher than 70%. Neither Hct 1 nor Hct 2 correlated with birth weight, gestational age, total blood solutes, or reticulocyte counts at birth in either group. An inverse linear correlation was found between blood pH at birth and Hct 2 in preterm newborn infants (r = 0.66, p less than 0.02). PMID- 1610944 TI - Effects of birth asphyxia on urinary organic acid excretion. AB - Using capillary gas chromatography-mass spectrometry, the effects of birth asphyxia on the urinary organic acid profile of term babies was investigated. Random urine samples were collected on days 1 and 8 from 19 babies with fetal distress, 19 with moderate birth asphyxia and 12 with severe asphyxia causing encephalopathy. Controls were 27 well neonates. Statistically significant abnormalities were found only for the severely asphyxiated group: increased concentrations of lactic, pyruvic, 3-hydroxybutyric, 4-hydroxyphenyllactic and 4 hydroxy-3-methoxymandelic acids, and excretion of four abnormal metabolites, 2 hydroxybutyric, 2-oxoisocaproic, 2-hydroxyisovaleric and 2-oxo-3-methylvaleric acids. Six other babies had increased lactic acid excretion, associated in four with transient 'jitterness' or hypotonia. Organic acid studies may help to grade the severity of perinatal asphyxia in the outcome or intervention studies. PMID- 1610946 TI - Comparative study of the binding of prolactin and growth hormone by rabbit and human lung cell membrane fractions. AB - The specific binding capacities for human prolactin (hPRL) and human growth hormone (hGH) were examined in human lung membrane preparations at different developmental stages. A parallel study was carried out on rabbit lung preparations to compare binding parameters. Lung tissues were obtained from 15 fetuses of 16-38 weeks after spontaneous or therapeutic abortion and from 7 adults (lobar resection surgery). A histological study was systematically performed with a radial alveolar count in the fetuses with suspected hypoplasia. Binding analysis was performed on both intact membrane preparations and MgCl2 treated membranes, using [125I]hGH and [125I]hPRL as tracers. In the rabbit lung, specific [125I]hGH binding was found. Scatchard analysis revealed a single class of binding sites (affinity constant: 2.6 +/- 0.8 x 10(9) l/nmol and number of binding sites: 9.5 +/- 4.3 fmol/mg protein for adult rabbit; 1.85 +/- 0.5 x 10(9) l/nmol and 27.6 +/- 3.0 fmol/mg protein for 25-day-old rabbit fetuses, respectively). In contrast, [125I]hPRL did not specifically bind to lung membrane preparations. In the human lung, no consistent specific binding sites for [125I]hPRL or [125I]hGH (less than 0.5%/mg protein) were detected in adults and in 11 of the 15 fetuses. In 4 fetuses, little specific binding was observed (0.59 1.9%/mg protein) for [125I]hGH and (1.5%/mg protein) for [125I]hPRL. There was no correlation with histological lung structure. Our findings confirm the presence of specific binding sites for GH in the adult rabbit lung and demonstrate such binding in the fetal rabbit lung. In contrast, our results showed no significant binding for PRL and GH in the human lung, suggesting that these hormones do not play a direct physiological role in human lung growth and maturation. PMID- 1610947 TI - Interactive ventilatory effects of two respiratory stimulants, caffeine and doxapram, in newborn lambs. AB - Caffeine and doxapram are two respiratory stimulants used in the treatment of apnea in newborns. When used concurrently, these drugs may produce interactive effects on the control of breathing in the newborn. The ventilatory effects of these drugs, given alone or together, were measured during 150 min of drug infusion in two groups of awake lambs 2-5 days old. The first group (n = 5) received a caffeine loading dose of 10 mg/kg followed by a maintenance dose of 0.1 mg/kg/h and incremental doses of doxapram: 0.25, 0.5, 1.25 and 2.5 mg/kg/30 min. The second group (n = 5) received a doxapram loading dose of 5.5 mg/kg followed by a maintenance dose of 1 mg/kg/h and incremental doses of caffeine: 2.5, 5.0, 7.5 and 10.0 mg/kg/30 min. In the first group, ventilation increased after the caffeine loading dose from 566 +/- 55 to 680 +/- 74 ml/kg/min (plasma caffeine = 14.7 +/- 1.6 mg/l) and progressively increased with the addition of incremental doses of doxapram up to 1,000 +/- 108 ml/kg/min at 2.5 mg/kg of doxapram (p less than 0.001 compared to baseline and caffeine loading dose). In contrast, in the second group, the doxapram loading dose markedly increased ventilation from 582 +/- 50 to 936 +/- 75 (p less than 0.002 and p less than 0.04 compared to caffeine loading dose) at plasma doxapram of 5.3 +/- 0.8 mg/l, but incremental doses of caffeine had no effects. We conclude that doxapram exerts a brisk and powerful respiratory stimulant effect and produces an additional dose dependent ventilatory response when added to caffeine. PMID- 1610949 TI - Adrenal function in preterm infants. AB - The adrenal function of 10 preterm infants of gestational age 27-34 weeks was assessed longitudinally from measurements of excretion rates of steroid metabolites in 24-hour urine samples collected at frequent intervals for up to 80 days after delivery. The changes in steroid excretion with time in preterm infants of gestation over 28 weeks reflect involution of the fetal adrenal zone at a similar rate to term infants. These findings are consistent with the removal at birth of the inhibitory effects of oestrogen on the 3 beta-hydroxysteroid dehydrogenase enzyme. The continued function of the adrenal fetal zone beyond the first month in preterm infants of less than 28 weeks gestation may however be due to persistence of some other fetal regulatory adrenal mechanism. PMID- 1610948 TI - Doxapram for the initial treatment of idiopathic apnea of prematurity. AB - The ventilatory effects of doxapram in the initial pharmacotherapy for apnea in the newborn were evaluated in 8 premature infants with idiopathic apnea. All received doxapram for 48 h at 0.25 mg/kg/h on the first day and 1 mg/kg/h on the second day. The ventilatory effects and the airway occlusion pressure (p0.1) were measured by means of a face mask, and a pneumotachograph. Compared to the pretreatment period, the mean of the frequency of central apnea greater than or equal to 15 s decreased significantly (p less than 0.01) by 48 and 75% during the first and second day, respectively. Both doses significantly increased inspiratory drive measured by airway occlusion pressure by 20% (p less than 0.05) and 32% (p less than 0.01) on the first and second day of drug treatment, respectively. Minute ventilation, tidal volume and mean respiratory flow significantly increased only with 1 mg/kg/h of doxapram, accompanied by a significant decrease in transcutaneous PCO2. No side effects were noted. Data suggested that doxapram alone at a dose of 1 mg/kg/h is effective for the treatment of neonatal apnea. PMID- 1610950 TI - Prostaglandin E1, E2, and F2 alpha in human milk and plasma. AB - Concentrations of prostaglandin E1, E2, and F2 alpha (PGE1, PGE2, and PGF2 alpha) were determined in milk and plasma from mothers of 9 preterm and 11 term infants. The concentration of PGE1 in milk was similar to that in plasma, and the concentrations of PGE2 and PGF2 alpha were approximately 1.2-2 times higher than those in plasma. However, no significant differences in the levels of PGE1, PGE2, and PGF2 alpha were observed between the foremilk and hindmilk, among the colostrum, transitional milk, and mature milk, and between preterm and term milk. Further studies have to be performed to confirm that the stable levels of PGE1, PGE2, and PGF2 alpha in human milk found in this study play an important role in the gastrointestinal function of infants. PMID- 1610951 TI - Nutrient levels in amniotic fluid from women with normal and neural tube defect pregnancies. AB - We analyzed nutrient levels in amniotic fluid obtained during the second trimester of normal, uncomplicated pregnancies from 221 women who delivered apparently healthy infants and from 8 with neural tube defect (NTD) pregnancies. Folate was measured by microbiological assay, vitamin B12 by a radiobinding method, and zinc, copper and iron by atomic absorption spectrophotometry. We found that the mean amniotic fluid nutrient levels of normal pregnancies were 24.7 nmol/l for folate, 600 pmol/l for vitamin B12, and 1.7, 1.9, and 9.0 mumol/l for zinc, copper and iron, respectively. Amniotic fluid folate, zinc, copper and iron levels of NTD pregnancies were similar to those found during normal pregnancy, however, vitamin B12 levels were markedly lower than those of normal pregnancies. PMID- 1610952 TI - Breast milk beta-glucuronidase and exaggerated jaundice in the early neonatal period. AB - Breast-feeding is associated with jaundice in the early neonatal period. Previous work has shown levels of the enzyme beta-glucuronidase in maternal breast milk to be related to infant serum bilirubin on postnatal day 21. Our aim was to establish if there was a correlation between the level of breast milk beta glucuronidase and the degree of early (first week) neonatal hyperbilirubinaemia. A study of 55 mother and baby pairs showed that breast milk beta-glucuronidase levels had no relationship with the level of infant serum bilirubin between postnatal days 3 and 6. Breast milk beta-glucuronidase does not directly account for the early neonatal jaundice seen in breast-fed babies. PMID- 1610953 TI - Hyperglycemia and the rate of lactic acid accumulation during cerebral ischemia in developing animals: in vivo proton MRS study. AB - During cerebral ischemia, hyperglycemia has a deleterious effect upon the adult brain but not the neonatal brain. This phenomenon may be related to the fact that hyperglycemia in adult animals subjected to cerebral ischemia raises the ischemic accumulation of lactate by as much as 10-fold. The purpose of this study was to determine whether hyperglycemia during cerebral ischemia produces a similar increase in the rate of lactic acid accumulation in developing animals. Data from in vivo proton magnetic resonance spectroscopic experiments showed that blood glucose concentration did not affect the rate of lactic acid accumulation during cerebral ischemia in either the neonatal dog or juvenile rabbit. The lack of increase in the ischemic rate of lactic acid accumulation during hyperglycemia in the developing animal contrasts sharply with the marked effect of blood glucose concentration upon the rate of lactic acid accumulation in the adult animal. Differences in the total amount of lactic acid formed and the rate at which it is accumulated may contribute, in part, to the greater tolerance of the young animal to cerebral ischemia. PMID- 1610954 TI - Ultrastructural studies on bone marrow development in embryonic mice. AB - The hematopoietic events in the embryonic C57B1/6J mouse bone marrow have been followed by electron microscopy. The first type of cells to appear in the embryonic bone marrow were mesenchymal cells identified at day 15 of gestation. The first recognisable hemopoietic cells to appear were those of the granulocytic series identified as mature cells at day 18, although single red cell precursors were also found at this gestational stage. The real erythroid development was noted on the last days of gestation (days 20 and 21), when also cells of the megakaryocytic series were found. At birth, day one of newborn life, all hematopoietic elements were present. The pattern of hematopoietic development in the embryonic bone marrow was compared to that observed in other embryonic hematopoietic sites. PMID- 1610955 TI - Assay for opsonin activity based on chemiluminescence of a Cypiridina luciferin analog. AB - Opsonin activity (OA) was investigated in serum samples from cord blood of 11 full-term newborn infants and 12 healthy adult volunteers by the method of luminol-dependent chemiluminescence (L-CL) and Cypiridina luciferin analog dependent chemiluminescence (CLA-CL) together with the measurement of complement components (C3, C4, C3A and properdin). CL and complement components of cord samples were significantly lower than that of healthy adult blood. CLA-CL showed a significant correlationship to C3 and C3A. L-CL also displayed a significant correlationship to C3A but the relationship to C3 was not significant. From these results, when OA is measured by CL, CLA-CL is preferred to L-CL as a technique. PMID- 1610956 TI - Anticoagulant effects of sulphonated polyurethanes. AB - Sulphonated polyurethanes have been shown to have excellent blood contacting properties. In this paper, similar polyurethanes which are water soluble have been investigated to determine their influence on thrombus formation. These polymers were shown to delay clotting times in the following ways: by direct complex formation between the polymer and thrombin; by interference with fibrin polymerization; and by complex interactions between polymer, thrombin, plasma antiproteases and fibrinogen in plasma. PMID- 1610957 TI - Chemical modification of bovine pericardium and its effect on calcification in the rat subdermal model. AB - Specific modification of functional groups in collagen has been used to investigate their influence on calcification and thermal stability of bovine pericardium. Pretreatment of pericardium with iron (III) citrate reduced calcification in the rat subcutaneous implant model, as did acyl azide activation of carboxyl and amide groups. Chondroitin sulphate had no significant effect, while cyanamide treatment was mainly effective in combination with iron (III) citrate. Glutaraldehyde pretreatment restricted reaction with other modifying agents, but, as a post-fixation treatment, improved the thermal stability of other agents. Glutaraldehyde post-fixation had no significant relationship to the calcification rate. PMID- 1610958 TI - Mechanical properties and histology of charge modified bioprosthetic tissue resistant to calcification. AB - Modification of bioprosthetic heart valves tissue by covalently binding protamine sulphate, results in stable covalent links of protamine to the tissue, conferring resistance to calcification. We report here the morphological evaluation and mechanical properties (elastic modulus and ultimate tensile strength) of protamine-bound bioprosthetic tissue that have high anticalcification potential. Protamine-bound bioprosthetic tissue had significantly higher tissue modulus and ultimate tensile strength values than control tissue groups. However, the mechanical properties and tissue architecture were inferior to those of bioprosthetic tissue. PMID- 1610959 TI - Haemocompatibility of polymer having phospholipid polar groups evaluated by monoclonal antibody method. AB - The haemocompatibility of a polymer having the phospholipid polar group, poly(2 methacryloyloxyethyl phosphorylcholine (MPC)-co-n-butyl methacrylate(BMA)), was evaluated by a monoclonal antibody SZ-21 (directing specifically against the membrane glycoprotein complex IIIa of human platelet) radioimmunoassay method. The study showed that poly(MPC-co-BMA) possessed better haemocompatibility than segmented polyurethane (SPEU). Radioactivity of platelets adhered (counts per min/cm) on a polyethylene (PE) tube coated with poly(MPC-co-BMA) was 19.51 +/- 5.58, with albumin; 20.05 +/- 7.29, with SPEU having sulphonated group; 76.10 +/- 18.9, with SPEU; 287.0 +/- 95.0, PE treated by plasma irradiation; 2091 +/- 261, and original PE was 1772 +/- 116. The results were further certified by scanning electron microscopic observations. PMID- 1610961 TI - Studies of surface activated coagulation: antisera binding onto methyl gradients on silicon incubated in human plasma in vitro. AB - Human plasma proteins factor XII, high molecular weight kininogen, prekallikrein, factor XI and fibrinogen, participate in surface-initiated coagulation. Antisera binding to methyl gradients made on hydrophilic silicon was studied after immersion in normal and deficient human blood plasma. Scanning ellipsometry was used to quantify the adsorbed organic material. The hydrophilic part of the gradient deposited anti-factor XII and anti-high molecular weight kininogen, but low amounts of anti-fibrinogen. Increased amounts of anti-fibrinogen bound onto the hydrophobic part, and the intermediate gradient region with mixed polar nonpolar surface characteristics bound low amounts of anti-factor XII, anti-high molecular weight kininogen and anti-fibrinogen. Tentatively, in this gradient region, simultaneous polar and non-polar surface characteristics result in a low level of surface-activated coagulation. Surfaces immersed in heparinized-and EDTA plasma indicate different antisera depositions. PMID- 1610960 TI - Hydrogels in endovascular embolization. V. Antitumour agent methotrexate containing p(HEMA). AB - The aminohexyl derivative of the copolymer of 2-hydroxyethyl methacrylate and ethylene dimethacrylate (p(HEMA)-Hex) in the form of regular spherical particles was used as a polymeric carrier for chemically sorbed methotrexate (MTX). The effect of the washed p(HEMA)-Hex-MTX carrier on the morphological structure of donor blood, on blood coagulation indicators and on responses of the living tissue surrounding the material which has been in the blood vessel of the rabbit for various periods of time was evaluated. MTX is capable of diffusion for several days from the embolic material. PMID- 1610962 TI - Interaction of thrombin with synthetic fluorescent substrate immobilized on polymer membrane. AB - Synthetic fluorescent substrates for thrombin were immobilized on a polyurethane membrane. The interaction of thrombin with the immobilized substrates was investigated. Upon hydrolysis of immobilized substrates by thrombin, fluorescence was emitted, intensity increasing linearly with time. From a Lineweaver-Burk plot, kinetic parameters of the enzyme reaction on the membrane surface were determined. The dissociation constant (K) was increased and the catalytic constant (k) decreased markedly by immobilization. More reactive thrombin substrates in solution were also more reactive in the immobilized state. More thrombin was adsorbed and adsorbed thrombins were inactivated more strongly on the surface with more reactive substrates when immobilized. The immobilization of thrombin substrate markedly suppressed fibrin formation on the membrane surface and made the membrane non-thrombogenic. PMID- 1610963 TI - Behaviour of fetal rat osteoblasts cultured in vitro on bioactive glass and nonreactive glasses. AB - We examined the behaviour of fetal rat osteoblasts cultured upon bioactive glass and nonreactive glasses, and the supposed stimulatory effects of bioactive glass on osteoblasts. Nonreactive glass cultures showed flattened cells with almost no dorsal ruffles. Bioactive glass cultures showed compact cells with dorsal ruffles and filapodia resulting in the formation of a denser cell layer. For confluent nonreactive glass cultures the osteoblast expression was mainly concentrated in the clustered cells which were formed upon the monolayer, whereas for confluent bioactive glass cultures the osteoblast expression was more generally distributed. The production of type I collagen, osteocalcin and an osteoblast specific antigen was shown by immunocytochemistry for all cultures, although differences in distribution were observed. The bioactive layer of bioactive glass is responsible for a better osteoblast-like morphology, a higher proliferation rate and generally a better osteoblast expression. PMID- 1610964 TI - Influence of substituting B2O3 for CaF2 on the bonding behaviour to bone of glass ceramics containing apatite and wollastonite. AB - Glass-ceramics containing crystalline oxy-fluoroapatite (Ca10(PO4)6(O,F2)) and wollastonite (CaSiO3) (designated AWGC) are reported to have a fairly high mechanical strength as well as the capability of forming a chemical bond with bone tissue. The chemical composition is MgO 4.6, CaO 44.9, SiO2 34.2, P2O5 16.3, and CaF2 0.5 in weight ratio. In this study the influence of substituting B2O3 for CaF2 on the bonding behaviour of glass-ceramics containing apatite and wollastonite to bone tissue was investigated. Two kinds of glass-ceramics containing apatite and wollastonite were prepared. CaF2 0.5 was replaced with B2O3 at 0.5 and 2.0 in weight ratio (designated AWGC-0.5B and AWGC-2.0B). Rectangular ceramic plates (15 x 10 x 2 mm, abraded with No. 2000 alumina powder) were implanted into a rabbit tibia. The failure load, when an implant detached from the bone, or the bone itself broke, was measured. The failure load of AWGC 0.5B was 8.00 +/- 1.82 kg at 10 weeks after implantation and 8.16 +/- 1.36 kg at 25 weeks after implantation. The failure load of AWGC-2B was 8.08 +/- 1.70 kg at 10 weeks after implantation and 9.92 +/- 2.46 kg at 25 weeks after implantation. None of the loads for the two kinds of glass-ceramics decreased as time passed. Giemsa surface staining and contact microradiography revealed direct bonding between glass-ceramics and bone. SEM-EPMA showed a calcium-phosphorus rich layer (reaction zone) at the interface of ceramics and bone tissue. The thickness of the reaction zone was 10 to -15 microns and did not increase as time passed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610965 TI - Cutaneous melanoma at Lawrence Livermore National Laboratory: comparison with rates in two San Francisco bay area counties. AB - During the period 1974 through 1985, employees at Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States) were diagnosed with cutaneous malignant melanoma at approximately three times the rate of the surrounding community. We investigated two explanations for this excess: the first explanation examined was that the recorded incidence of the neighboring community underestimates actual incidence. We estimated the amount of excess attributable to underreporting by using data from a survey conducted among San Francisco Bay Area clinicians and pathologists to determine previously unrecorded occurrences. We found that underreporting has negligible impact on melanoma incidence. The second explanation examined was that heightened medical awareness of the disease among LLNL employees and their physicians has led to greater detection. We found that LLNL melanomas are thinner than those from the surrounding community and that no excess was observed if we limited our attention to thicker, more invasive melanomas. PMID- 1610967 TI - Dietary beta-carotene, cigarette smoking, and lung cancer in men. AB - A cohort of 5,080 men living in a retirement community in California (United States) and initially free from lung cancer were followed from June 1981 to December 1989. At recruitment, each study participant completed a mailed questionnaire which requested information on the subject's medical history, use of cigarettes, and usual consumption frequencies during the preceding 12 months of 44 vegetable and fruit items. Men who had never smoked had the highest mean daily intake of beta-carotene (8,505 micrograms), followed by past smokers (7,761 micrograms) and then by current smokers (6,178 micrograms). beta-Carotene intake of the subject's wife was correlated significantly with that of the husband in the 4,018 spouse pairs (r = 0.46; P = 0.0001). Among men with similar smoking habits, dietary beta-carotene intake significantly decreased with the spouse's smoking habit: never, past, and current smokers (P = 0.004; test for linear trend). During 31,477 person-years of follow-up, 125 incident cases of lung cancer were observed among the cohort of 5,080 men. Age-adjusted relative risks for lung cancer were below unity (i.e., demonstrating a reduced risk) for higher relative to lower consumption of beta-carotene, of all vegetables and fruits, and of yellow vegetables alone. However, these relative risks approached or crossed the null value when adjusted for personal smoking. PMID- 1610966 TI - Oral contraceptive use and risk of cutaneous malignant melanoma in a case-control study of French women. AB - We report the results of a case-control study designed to analyze the relationship between oral contraceptive use (OC) and the risk of cutaneous malignant melonama (MM) in 240 White women under the age of 45. Five French centers participated in the study between February 1982 and January 1987 for periods of eight to 54 months, depending on the center. Cases were 91 consecutive newly diagnosed patients with histologically verified MM. Each case was matched with one or two controls on year of birth, date of interview, and treatment center. Controls were 149 patients with either malignant or nonmalignant disease who came to the center for diagnosis and treatment. Odds ratios (OR) were estimated by multivariate analyses taking into account age at menarche, sunlight exposure, and skin characteristics. No significant relation was found between the risk of MM and the total duration of OC use, age at start of use, and elapsed time since the first OC use. However, when the analysis was restricted to women aged 30-40 years, i.e., those who were able to use OC for 10 years or more, or who had started OC use 15 years or more before the diagnosis, the risk of MM increased significantly with the duration of OC use (P = 0.03). A total of more than 4,000 hours of sunlight exposure, and menarche before the age of 14 also were found to increase significantly the risk of MM (OR = 5.4, 95 percent confidence interval [CI] = 1.6-18.3; and OR = 3.6, CI = 1.0-12.5, respectively). PMID- 1610968 TI - Stomach cancer patterns in European immigrants to Connecticut, United States. AB - Age-adjusted annual incidence rates of stomach cancer (ICD-9 code #151) were examined for the period 1973-88 among Connecticut residents who were born in the United States or who emigrated from one of five European nations (Italy, Poland, the United Kingdom, Germany, Portugal). Risk of stomach cancer among each of the five immigrant groups was elevated significantly above that of US-born residents. The magnitude of difference ranged from a 1.62-fold excess among persons born in Italy to a 4.27-fold increase in risk among persons born in Portugal. Cancer risk to foreign-born residents was less than that observed in their native countries, with decreases of 25-64 percent found here. Several differences in patient and disease characteristics were observed according to country of birth. Compared with US-born residents, there was a lesser predominance of males among patients born in Italy, Poland, and the UK. Among all foreign-born groups, the gastric cardia was involved less frequently, and the pyloric region more frequently, than in US-born patients. Adenocarcinomas were significantly less common among Polish born cases. The findings suggest different etiologies in foreign and US-born patients. PMID- 1610969 TI - Survival for lung cancer in northern Italy. AB - From the population covered by the Lombardy Cancer Registry (northern Italy), all 2,259 lung cancer patients diagnosed from 1976 to 1981 were followed through 30 November 1989. The length of follow-up ranged from eight to 13 years. A special investigation on long-term survivors showed that a negligible proportion (0.01 percent) of errors occur in determining life status when an active follow-up is adopted. Age, stage, and histotype were found to be statistically significant, independent, prognostic factors in multivariate analysis both by the Cox model and by a model considering the relative survival. Observed survival was 29 percent at one year after diagnosis, 13 percent at two years, eight percent at three years, five percent at five years and two percent at 10 years. Survival decreased with age, but the youngest patients of both sexes showed lower survival compared with immediately subsequent ages. Among morphologically confirmed tumors, epidermoid carcinomas and adenocarcinomas showed the highest survival (38 percent and 33 percent at one year, respectively); small cell carcinomas showed the poorest prognosis (one-year survival, 23 percent). Beyond the second year after diagnosis, differences between histotypes became slighter. Survival according to stage showed a decreasing pattern from limited to advanced tumors, one-year figures being 41 percent for localized tumors, 27 percent for regional metastasis, and three percent for distant metastasis. Relative survival in Varese was compared with that reported by other cancer registries in Western countries: the variability noted could be related to different modalities of registration and to different distribution of clinical and demographic factors. PMID- 1610970 TI - Heterogeneity in the clastogenic response to X-rays in lymphocytes from ataxia telangiectasia heterozygotes and controls. AB - A coded analysis of X-ray-induced chromatid aberrations in lymphocyte cultures from 45 control individuals and 19 ataxia-telangiectasia (A-T) heterozygotes was performed. The distribution of chromatid breaks induced in the late G2 portion of the cell cycle by 60 cGy of X-rays appeared bimodal in the study population. In six controls (13 percent) and in 12 of 19 (63 percent) A-T heterozygotes, the yields of X-ray-induced breaks observed were within the higher mode of the distribution. However, lymphocytes from A-T heterozygotes sensitive to the induction of chromatid breaks by 60 cGy did not contain increased numbers of aberrations following exposure to 20 cGy. The radio-resistant inhibition of DNA synthesis that occurs in A-T homozygotes was not observed in heterozygotes. Co cultivation experiments showed an increased G2 delay in lymphocytes from an A-T heterozygote whose lymphocytes contained increased X-ray-induced chromatid breaks. The results show a significant association of A-T heterozygosity with G2 chromosomal sensitivity (P less than 0.001; Wilcoxon rank sum test). The measurement of X-ray-induced breaks, however, failed to identify 37 percent of A T heterozygotes tested. The predicted prevalence of increased sensitivity to X rays in controls is approximately three- to 30-fold greater than the estimated frequency of A-T heterozygotes in the general population. Therefore, although the increased sensitivity to X-ray-induced chromatid breaks appears to be associated with the A-T-gene, it is not a reliable indicator of A-T heterozygosity. Genetic or environmental factors other than the A-T gene also must be involved in the increased clastogenic response. PMID- 1610972 TI - Incidence of childhood malignancies in the vicinity of west German nuclear power plants. AB - The incidence of childhood malignancies in 20 areas surrounding major nuclear installations is compared with the incidence in matched control regions. The study is based on the registry of childhood malignancies in the Federal Republic of Germany and includes 1,610 cases which were diagnosed before 15 years of age from 1980 to 1990. The relative risk (RR) was 0.97 for all malignancies and 1.06 for acute leukemia in all regions within a 15 km radius of an installation. Increased RR was observed in subgroups for acute leukemia before five years of age and for lymphomas, especially in regions close to installations (less than 5 km) which started operation before 1970. Most of this increase was attributable to an unexpectedly low incidence in the control regions which could not be explained by analyzing possible confounding factors. Using the same control regions, a comparable and even more pronounced increase of RRs was observed in regions where nuclear power plants have been projected. PMID- 1610971 TI - A cohort study of tobacco use, diet, occupation, and lung cancer mortality. AB - In 1966, a cohort of White males aged 35 or over, who were policy-holders with the Lutheran Brotherhood Insurance Society (United States), completed a mail questionnaire on tobacco use, diet, and demographic characteristics. During the 20 years of follow-up, 219 lung cancer deaths occurred. Besides the strong relationship with cigarette smoking, we observed an effect on lung cancer risk among current users of cigars or pipes who were nonsmokers of cigarettes (relative risk [RR] = 3.5, 95 percent confidence interval [CI] = 1.0-12.6) or who were past/occasional users of cigarettes (RR = 2.7, CI = 1.4-5.3). In addition, elevated risks (from 1.5 to 2.6) of lung cancer were found among craftsmen and laborers, with the highest risks among subjects who worked in the mining or manufacturing industry. No association between current (as of 1966) use of beer or hard liquor and lung cancer was observed, although past users were at elevated risk. An inverse association between lung cancer and intake of fruits was observed, and risks of lung cancer were lower among persons in the highest dietary intake quintiles of vitamins A and C. Except for oranges, however, none of the inverse associations with fruits or dietary nutrients had statistically significant trends. The findings from this cohort study add to the evidence of an adverse effect of cigar/pipe smoking and possibly protective effect of dietary factors on lung cancer risk. PMID- 1610973 TI - Birth order and risk of testicular cancer. AB - To explore the etiology of testicular cancer, cases of testicular cancer were identified among members of a cohort of Danish boys born between 1941 and 1957 (inclusive), who had attended schools in Copenhagen and Gentofte and whose school health records were contained in an archive under the supervision of the Danish Cancer Registry. One hundred and eighty-three cases of testicular cancer diagnosed before 31 December 1984 were identified; 366 controls, matched to cases by sex and age, were selected from the same cohort. Information on potential risk factors and confounders was obtained from two sources: school health records and midwife protocols, both of which were recorded prior to the diagnosis of testicular cancer in cases. Relative risks (RR) approximated by the odds ratios were calculated and, in logistic regression analyses, adjustments were done for known or suspected confounders. A decreasing risk of testicular cancer with increasing birth order was observed (P = 0.020). Compared with being firstborn, being number four or more in birth order was associated with a significantly decreased RR for all testicular cancers (RR = 0.3, 95 percent confidence interval [CI] = 0.3-0.8) and testicular seminoma (RR = 0.1, CI = 0.02-0.9). No association was observed between high social class and the risk of testicular cancer (RR = 1.4, CI = 0.8-2.3); neither was age at which the study subjects had mumps or measles related to risk of testicular cancer. No cases of mumps orchitis were observed before or during school years. A slightly increased RR for testicular cancer among boys from small families could be explained by the association between family size and birth order.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610976 TI - An odyssey into the milieu interieur: pondering the enigmas. PMID- 1610975 TI - Leukemia clusters around nuclear facilities in Britain. PMID- 1610974 TI - Major histocompatibility complex, t-complex, and leukemia. AB - In experimental models, leukemia was the first disease shown to have an association with the major histocompatibility complex (MHC) genes. In humans, several allelic human-leukocyte antigen (HLA) associations also have been recognized. In addition to allelic associations, atypical HLA segregation patterns have been observed in leukemic families. These include a higher frequency of HLA-identical unaffected siblings, increased HLA homozygosity and increased maternal HLA-DR identity. These observations suggest preferential transmission of disease-associated haplotypes and a male transmission bias in leukemic families. The lack of disease-specific segregation, however, supports the idea that the HLA system is not directly relevant in leukemogenesis. Therefore, the existence of another genetic region linked to the MHC, causing segregation distortion, and containing recessive leukemia susceptibility genes may be postulated. The mouse t-complex would fit this model. This gene complex has recessive (semi-) lethal genes, is transmitted preferentially through fathers, and both the mouse t-complex and its rat homolog, growth and reproduction complex grc, confer susceptibility to carcinogenesis. This model could also explain the increased spontaneous abortion rate in mothers of leukemic patients, epidemiologic associations of leukemia with oral clefts and neuroectodermal tumors, and the transmission of a radiation-induced leukemia risk through fathers. Such segregation distortion might be the reason behind the maintenance of a gene(s) with a lethal effect in the population. PMID- 1610977 TI - A rat model of progressive chronic glomerular sclerosis: the role of thromboxane inhibition. AB - In order to evaluate a possible role of thromboxane A2 (TxA2) in the pathophysiology of chronic glomerular disease, we studied the effect of a 12-wk combined treatment with the thromboxane receptor blocker Daltroban (D) and the thromboxane synthesis inhibitor UK 38485 (UK) on glomerular function and morphology in a rat model of chronic progressive glomerular injury. The glomerular lesion was induced in unilaterally nephrectomized rats by the repeated i.v. injection of an antibody directed against mesangial cells. Control rats were uninephrectomized. Three months after the first antibody injection before D and UK treatment, albuminuria (35.8 +/- 3.6 mg/24 h) and glomerular TxB2 formation (146 +/- 20 pg/mg of protein/min) were significantly higher compared with control values (albuminuria, 14.3 +/- 3.5 mg/24 h; TxB2, 59 +/- 16 pg/mg/min). Six months after antibody, albuminuria in nephritic rats had increased to 135 +/- 17 mg/24 h. In nephritic rats treated with D plus UK, albuminuria (44 +/- 12 mg/24 h), however, was significantly (P less than 0.001) inhibited. Quantitative morphological analysis (glomerular damage index) 6 months after antibody revealed significantly (P less than 0.001) increased glomerular lesions in nephritic rats (0.353 +/- 0.095) compared with that in uninephrectomized controls (0.045 +/- 0.014). The treatment of rats with D and UK significantly (P less than 0.001) reduced the glomerular damage index (0.101 +/- 0.004) in nephritic rats. D plus UK treatment reduced glomerular TxB2 formation but increased prostaglandin E2 and 6-keto prostaglandin F1 alpha release by isolated glomeruli. This study demonstrates that interventional treatment with D and UK ameliorates albuminuria and glomerular morphological lesions in a rat model of immunologically induced progressive glomerular injury. PMID- 1610978 TI - Impaired myogenic responsiveness of the afferent arteriole in streptozotocin induced diabetic rats: role of eicosanoid derangements. AB - Evidence suggests that diabetes is associated with an impairment of renal autoregulation. It has previously been demonstrated that pressure-induced (myogenic) afferent arteriolar vasoconstriction is well preserved in the isolated perfused hydronephrotic kidney. In this study, pressure-induced afferent arteriolar vasoconstriction was examined in kidneys from streptozotocin-induced diabetic rats. Vessel diameters were measured by videomicroscopy as renal arterial pressure was elevated from 80 to 180 mm Hg. In normal kidneys, the afferent arteriole vasoconstricted progressively as renal arterial pressure was increased (-24 +/- 2% decrement in diameter at 180 mm Hg; N = 35; P less than 0.001). In contrast, afferent arterioles of diabetic kidneys exhibited a greatly attenuated response to pressure (i.e., -3 +/- 2% change at 180 mm Hg; N = 60). In vitro treatment with 100 microM ibuprofen completely restored myogenic vasoconstriction (-21 +/- 2% change at 180 mm Hg), but did not alter myogenic responses of control (i.e., nondiabetic) kidneys. The control of hyperglycemia by insulin treatment resulted in a partial preservation of myogenic vasoconstriction (i.e., -11 +/- 3% change at 180 mm Hg), which was further restored by the administration of a low dose (10 microM) of ibuprofen (-21 +/- 1% change at 180 mm Hg). These observations indicate that diabetes is associated with an impaired responsiveness of the afferent arteriole to pressure that is mediated by an alteration in eicosanoid metabolism. This deranged renal microcirculatory response to pressure may represent a functional impairment of the diabetic kidney that may contribute to the progression of diabetic nephropathy. PMID- 1610979 TI - The role of disease duration and hypertension in albumin excretion of type I diabetes mellitus. AB - The objective of this study was to examine the relationship between blood pressure, albumin excretion, and renal function in patients with type I diabetes mellitus. The study design was as follows: nonselected consecutive patients with type I diabetes mellitus were divided into three groups by level of albumin excretion rate (AER): less than 20 micrograms/min, 20 to 200 micrograms/min, and greater than 200 micrograms/min. The setting for the study was an outpatient diabetic clinic in a tertiary referral center. There were 166 patients studied: 53% men, 47% women, 86% white, 17% treated for hypertension. Seventy-six percent had an AER less than 20 micrograms/min, 18% had an AER of 20 to 200 micrograms/min, and 6% had an AER of greater than 200 micrograms/min. Glycosylated hemoglobin did not differ between groups. AER was increased with age and disease duration (P less than 0.005 by analysis of variance) after 10 yr of disease. Serum creatinine (P less than 0.005) and systolic (P less than 0.005) and diastolic (P less than 0.01) blood pressures were also increased with AER. Serum creatinine and blood pressure were found to be increased in parallel after 10 yr of disease, but both remained within the normal range overall. A comparison of individual blood pressures in patients not taking antihypertensive drugs (N = 138) with age-related blood pressures of nondiabetic subjects revealed increased systolic and diastolic blood pressures at all ages. Group comparison demonstrated a significant link between increased AER and serum creatinine (declining renal function) and increased blood pressure after a latent period of 10 yr. Blood pressure appears to be increased from the earliest age in diabetes compared with healthy populations.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610980 TI - Effects of insulin and glucose on renal phosphate reabsorption: interactions with dietary phosphate. AB - Both insulin deficiency and glycosuria are known to inhibit the tubular reabsorption of phosphate. This inhibition has previously been evaluated either in the fasted state or on a normal phosphate diet. The goal of this study was to evaluate how dietary phosphate depletion affected the relative effects of insulin deficiency and glycosuria on the tubular reabsorption of phosphate. Rats were maintained on either a low- (0.03%) or normal (0.8%) phosphate diet. After 5 days, one half of the animals in each group received streptozotocin to induce short-term insulin deficiency, whereas the other half received vehicle alone. Two days later, sodium-dependent phosphate uptake by renal brush border membrane vesicles (BBMV) was evaluated in each of the four experimental groups. The effect of glucose on phosphate uptake was determined by the addition of varying concentrations of glucose (between 0 and 32 mmol/L) to the extravesicular transport fluid. BBMV phosphate uptake was about threefold higher in the nondiabetic rats fed a low-phosphate diet as compared with the nondiabetic animals maintained on a normal phosphate diet. In rats maintained on a low phosphate diet, streptozotocin treatment prevented the increase in BBMV phosphate transport; in contrast, in animals fed a normal phosphate diet, streptozotocin treatment had no effect on BBMV phosphate transport. Extravesicular glucose significantly inhibited phosphate transport in a dose-related manner, regardless of dietary phosphate or insulin status. Because fasting mimics the catabolic state associated with insulin deficiency, BBMV phosphate transport was also measured in rats fasted for 48 h after the administration of streptozotocin or vehicle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610981 TI - Mechanism of dopamine inhibition of renal phosphate transport. AB - Dopamine (DA) is natriuretic and phosphaturic. However, whether the effect of DA on Pi reabsorption is a consequence of its effect on sodium transport is not known. Therefore, this study was performed to determine the effect of DA on the maximal transport of phosphate (TmPi), and upon the capacity of renal proximal brush border membrane (BBM) for (Naextra-vesicular greater than Naintravesicular) gradient-dependent transport of Pi, as compared with the transport of other solutes. Graded infusions of Pi (0, 1, 2, and 3 mumols/min) were given to thyroparathyroidectomized male Sprague-Dawley rats in the presence of vehicle (0.9% NaCl; N = 5), DA 15 micrograms/kg/min; N = 6), or parathyroid hormone ((PTH); 1 U/kg/min; N = 5). The TmPi for rats infused with DA (3.3 +/- 0.3 mumol/mL) was significantly less than the TmPi for saline control rats (4.4 +/- 0.2 mumol/mL). Rats infused with PTH exhibited the lowest TmPi (1.8 +/- 0.3 mumol/mL). No differences in sodium excretion were observed among any of the groups. Na-dependent Pi transport was studied in BBM vesicles (BBMV) prepared from rats fed a low-phosphate diet for 2 days that were anesthetized, acutely thyroparathyroidectomized, and systemically infused with DA (350 micrograms bolus, plus 35 micrograms/kg/min; N = 8), PTH (33 U/kg bolus, followed by a continuous infusion of 1 U/kg/min; N = 6), or vehicle (1 mL/kg bolus, plus 2 mL/h constant infusion of 0.9% NaCl; N = 8) for 90 min. DA significantly inhibited the Na cotransport of Pi by 22.4 +/- 4.1% (P less than 0.01) as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610983 TI - Renal and systemic oxygen consumption in patients with normal and abnormal renal function. AB - Systemic and renal oxygen consumption and hemodynamics were studied in patients with normal renal function (NI; serum creatinine concentration (Screat), 1.0 +/- 0.04 mg/dL) and those with moderate chronic renal failure with diabetes mellitus Screat, 2.7 +/- 0.2 mg/dL) or without diabetes mellitus (Screat, 2.4 +/- 0.1 mg/dL). Patients with chronic renal failure were anemic and had normal systemic oxygen consumption (NI, 10,564 +/- 277; chronic renal failure, 9,669 +/- 362 mumol of O2/min) and elevated systemic oxygen extraction (NI, 22.9 +/- 1; chronic renal failure, 30.9 +/- 1.2%) (P less than 0.02). Cardiac output and index and arterial oxygen saturation were equivalent in normal patients and in patients with chronic renal failure. Patients with chronic renal failure had higher renal oxygen extraction (NI, 7.3 +/- 0.8; chronic renal failure, 13.9 +/- 1%), lower RBF (NI, 572 +/- 146; chronic renal failure, 197 +/- 20 mL/min/kidney), and lower renal oxygen consumption per kidney (NI, 391 +/- 101; chronic renal failure, 177 +/- 20 mumol of O2/min/kidney) than did normal patients (P less than 0.02). There was a linear relationship between hemoglobin and RBF (r = 0.47, P less than 0.02). Patients with chronic renal failure and diabetes had lower RBF (diabetes mellitus, 146 +/- 23; without diabetes, 242 +/- 28 mL/min/kidney) and renal oxygen consumption per kidney (diabetes mellitus, 131 +/- 21; without diabetes, 218 +/- 29 mumol of O2/min/kidney (P less than 0.03) but equivalent renal oxygen extraction when compared with patients without diabetes. Patients with chronic renal failure without diabetes mellitus had higher renal oxygen consumption when expressed per 100 mL of creatinine clearance (diabetes mellitus, 1,016 +/- 150; without diabetes mellitus, 1,453 +/- 175 mumol of O2/min/100 mL of creatinine clearance; P less than 0.03). There was a significant linear relationship (P less than 0.005, r = 0.38) between calculated creatinine clearance and renal oxygen consumption with a y intercept representing basal renal oxygen consumption (115 mumol of O2/min/kidney) and a slope of 2.3 mumol of O2/mL. Patients with moderate chronic renal failure have normal systemic oxygen consumption but reduced RBF and renal oxygen consumption. The latter parameters are even lower in patients with chronic renal failure and diabetes. Renal hypermetabolism is more likely to exist in nondiabetic than diabetic renal disease. Basic human renal physiology and pathophysiology are described by the relationships between renal oxygen consumption, blood flow, oxygen extraction, and creatinine clearance in patients with normal and abnormal renal function of varied cause. PMID- 1610982 TI - Renal artery stenosis: prevalence and associated risk factors in patients undergoing routine cardiac catheterization. AB - The purposes of this study were to determine the prevalence of angiographically significant renal artery stenosis in a patient population referred for diagnostic cardiac catheterization and to develop a model that predicts the highest-risk subset of patients who have significant renal artery narrowing. A prospective validation cohort study was undertaken in a referral-based university hospital. After left ventriculography, abdominal aortography was performed to screen for the presence of renal artery disease. A convenience sample of 1,302 of 1,651 consecutive patients undergoing diagnostic cardiac catheterization were enrolled in the study. Of the 1,302 abdominal aortograms performed, 1,235 (95%) were deemed of adequate quality for the evaluation of renal artery anatomy. Renal artery disease was identified in 30% of the patients. Insignificant renal artery stenosis was found in 187 (15%) and significant (greater than or equal to 50% diameter narrowing) stenosis was found in 188 (15%). Significant unilateral disease was present in 11%, and bilateral disease was present in 4%. By univariable and multivariable logistic regression analysis, the association of both clinically and catheterization-derived variables with renal artery disease was assessed. Multivariable predictors included age, severity of coronary artery disease, congestive heart failure, female gender, and peripheral vascular disease. Hypertension was not an associated variable. These data reveal the previously undetected high prevalence of renal artery disease in patients undergoing cardiac catheterization and provide clinical and angiographic features that assist in predicting its presence. PMID- 1610984 TI - Effect of n-3 fatty acids from fish oil on hemostasis, blood pressure, and lipid profile of dialysis patients. AB - Dialysis patients have an inordinate risk of cardiovascular events. Fish oils, rich in n-3 fatty acids, are believed to be beneficial in the prevention of atherosclerosis and thrombosis. Hence, the use of fish oils deserves consideration as a preventative or therapeutic intervention in dialysis patients. The suggestion has been made that n-3 fatty acids could increase the risk of bleeding, and thus, the safety of the use of these agents in dialysis patients must be established before long-term studies are undertaken. This study addresses the effect of n-3 fatty acids on the hemostatic profile of dialysis patients. Sixteen patients on chronic dialysis therapy were randomized to fish oil (MaxEPA) or placebo (olive oil) in a double-blind cross-over study. They received 3.6 g of n-3 fatty acids for 4 wk. Bleeding times were 4.8 +/- 0.4 min on MaxEPA and 4.5 +/- 0.3 min on placebo. Platelet aggregation to low-dose ADP or collagen also remained unchanged. There was a trend to lower serum triglyceride levels (2.7 +/- 0.5 versus 3.4 +/- 0.6 mmol/L, fish oil versus placebo) that did not reach statistical significance. Gastrointestinal side effects occurred in 10 of the 16 subjects and were severe in 5 patients. These side effects occurred in both the olive oil and the fish oil groups. The study had a 95% chance of detecting a clinically doubling significant increase in bleeding time, i.e., beta error less than 5%. In conclusion, n-3 fatty acids do not introduce a clinically important risk of bleeding for patients with end-stage renal disease. PMID- 1610985 TI - Renal function at hospital admission as a prognostic factor in adult hemolytic uremic syndrome. The Italian Registry of Haemolytic Uremic Syndrome. AB - The clinical records of adult patients with a diagnosis of hemolytic uremic syndrome were retrospectively reviewed with the aim of evaluating the long-term outcome of renal function. The setting is the Italian Registry of Haemolytic Uraemic Syndrome, with which 13 Nephrology Centers have participated. Clinical and laboratory data of 43 patients with hemolytic uremic syndrome were evaluated. The mean age at onset was 34.3 +/- 18.3 yr. Men and women were equally affected. No seasonal trend in presentation was observed. In 20 patients, hemolytic uremic syndrome was primitive, whereas in 23, it was associated with another disease (cancer, preeclampsia, malignant hypertension, vasculitides). Gastrointestinal symptoms were the most frequently observed prodromes. Thirty (70%) patients required dialysis during the acute phase of the disease. Six patients died during the acute phase of the disease, and one died later after discharge (overall mortality, 16%). After 1 yr of follow-up, 11 (26%) patients had recovered a normal renal function, 14 (33%) had hypertension and/or renal insufficiency, and 11 (26%) were on regular dialysis. When prognostic factors of survival and recovery of renal function were considered, it was found that older age was associated with higher mortality in the acute phase, whereas severe renal involvement at the onset of the disease (as expressed by elevated serum creatinine) was associated with a long-term unfavorable prognosis. PMID- 1610986 TI - Continuous cardiac output measurements in critically ill patients. PMID- 1610987 TI - Halothane or isoflurane for infrarenal aortic cross-clamping? PMID- 1610988 TI - Continuous thermodilution cardiac output measurement in intensive care unit patients. AB - A new continuous thermodilution cardiac output measurement technique and companion flow-directed pulmonary artery catheter were evaluated in intensive care unit (ICU) patients. Continuous cardiac output was monitored for 6 hours in each patient, and, at selected intervals, a series of bolus thermodilution cardiac output determinations was made and averaged for comparison. A total of 222 data pairs was obtained in 54 patients. The cardiac outputs ranged from 2.8 to 10.8 L/min. The linear regression is represented by the following equation: continuous thermodilution = 0.99 bolus thermodilution + 0.02. The correlation coefficient r was 0.94, the Syx was 0.54. The mean relative error was 0.3%, and the standard deviation of the relative error was 11.5%. The absolute measurement bias was 0.02 L, and the 95% confidence limits were 1.07 and -1.03 L. The results demonstrated that the new continuous thermodilution cardiac output measurement technique provided acceptable accuracy and was considerably easier to use in the clinical situations studied in the ICU. PMID- 1610989 TI - Indications for the use of pacing pulmonary artery catheters in cardiac surgery. AB - Several varieties of pulmonary artery catheters (PACs) with pacing capabilities are now available. Although specific recommendations for prophylactic perioperative placement of pacemakers have been offered previously, the authors believe that those recommendations warrant further examination, taking into consideration the availability of new pacing modalities. Toward this end, the use of pacing PACs in cardiac surgical patients was prospectively examined. In 600 consecutive adult patients with PACs placed prior to cardiopulmonary bypass (CPB), the cardiac anesthesiologist recorded if a pacing PAC was placed, the indications for placing it, and whether the catheter was used to pace. If a pacing PAC was not chosen, the anesthesiologist indicated whether cardiac pacing was needed prior to CPB. In all patients, the presence and specifics of the following five possible indications were documented: sinus node dysfunction/bradydysrhythmias, atrioventricular heart block, fascicular or bundle branch block, cardiac reoperation, and/or valvular heart disease. PACs with pacing capability were placed in 180 of the 600 patients (30.0%) and were used in 34 of these 180 patients (18.8%). In 4 of 420 patients (0.95%) without pacing PACs, cardiac pacing was needed prior to CPB. The following preoperative diagnoses were significant predictors (P less than .05) for the use or need for pacing catheters: sinus node dysfunction/bradydysrhythmias, a history of transient complete atrioventricular block, aortic stenosis, aortic insufficiency, and reoperation. The majority of adult patients undergoing cardiac surgery do not require the use of a pacing PAC prior to CPB.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1610990 TI - Perioperative evaluation of a new mixed venous oxygen saturation catheter in cardiac surgical patients. AB - Fiberoptic pulmonary artery flotation catheters have gained clinical acceptance for continuous monitoring of mixed venous oxygen saturation (SvO2), especially in the management of hemodynamically unstable patients. Therefore, the performance of the oximetry system used is extremely important. The accuracy and stability of a new two-wavelength oximetry pulmonary artery catheter and SAT-2 oximeter were assessed in adult patients during and following cardiac surgery. After in vitro calibration of the system, the catheter was inserted through the right internal jugular vein and positioned in the pulmonary artery prior to induction of anesthesia. During the study period, the system was updated for hemoglobin changes of 1.8 g/dL or more. In vivo SvO2 values obtained by the oximetry catheter were compared with those determined with a reference oximeter from simultaneously drawn mixed venous blood specimens at different intervals. A total of 604 paired data points from 52 patients were analyzed, 572 (94.7%) of which were within the 95% confidence interval. Overall bias was -1.7% +/- 3.5% (SD). The results suggest that over the time course of the study, in vivo SvO2 values obtained with the two-wavelength catheter and the SAT-2 oximeter closely approximated SvO2 measured with a reference oximeter from mixed venous blood samples (r = 0.917; SEE 3.5%) in cardiac surgical patients in whom marked physiological changes occur. PMID- 1610991 TI - Continuous monitoring of mixed venous oxygen saturation during orthotopic liver transplantation. AB - Hemodynamic management is an important issue concerning anesthesia for orthotopic liver transplantation (OLT). Mixed venous oxygen saturation (SvO2) is considered a good index of tissue oxygenation, but controversy exists about the usefulness of monitoring this parameter in different types of surgery. Therefore, a prospective study was performed to determine changes in SvO2 during OLT and to study the correlation between SvO2 and hemodynamic measurements. Thirty patients undergoing transplantation for end-stage liver disease were divided into two groups: group 1 (n = 15, aged 42 +/- 11 years [mean +/- SD]) without venovenous bypass (VVB), and group 2 (n = 15, aged 43 +/- 10 years) with VVB. SvO2 was greater than 74% throughout the procedure and remained stable during dissection and the anhepatic phase. There was a significant increase in SvO2 after unclamping the portal vein in group 1, whereas a significant decrease was observed during the first hour following reperfusion in group 2. There was no correlation among SvO2 and oxygen consumption, arterial oxygen saturation, (SaO2), or hemoglobin concentrations. A statistically significant correlation was found between SvO2 and cardiac index in both groups (group 1: r = 0.58, P = 0.01; group 2: r = 0.51, P = 0.01), but the correlation was relatively poor. Continuous monitoring of SvO2 may be useful, but cannot substitute for intermittent determinations of other hemodynamic or oxygenation parameters. PMID- 1610992 TI - Right ventricular function in patients with aortic stenosis undergoing aortic valve replacement. AB - The effects of aortic stenosis (AS) on right ventricular function during cardiac surgery are not fully understood. Forty patients undergoing aortic valve replacement with either a systolic transvalvular gradient of less than 100 mm Hg (82.1 +/- 5.5 mm Hg; group 1, n = 20) or greater than 120 mm Hg (131.1 +/- 6.9 mm Hg, group 2, n = 20) were investigated with regard to right ventricular function in the perioperative period. Right ventricular ejection fraction (RVEF), right ventricular end-systolic volume (RVESV), and right ventricular end-diastolic volume (RVEDV) were measured by means of the thermodilution technique. Before cardiopulmonary bypass (CPB), RVEF was significantly lower in group 2 patients (34% +/- 6%) than in group 1 (45% +/- 5%). After CPB, RVEF increased significantly in group 2 (28% +/- 4% to 49% +/- 5%), and no further differences were noted between the groups. In the patients with a higher systolic transvalvular gradient, RVEDV and RVESV were lower at the start of surgery, but increased after opening the pericardium. Cardiac index was also lower in these patients. Pericardiotomy resulted in a decrease in right ventricular end-systolic pressure (RVESP) only in the patients of group 2. In these patients more epinephrine was necessary to maintain stable hemodynamics during the post-bypass period. It is concluded that patients with AS are at risk of reduced right ventricular function when the systolic transvalvular pressure gradient is more than 120 mmHg. Knowledge of the complex interaction between the two sides of the heart may enable anesthesiologists to optimize management during the perioperative period. PMID- 1610993 TI - EEG power changes are more sensitive than spectral edge frequency variation for detection of cerebral ischemia during carotid artery surgery: a prospective assessment of processed EEG monitoring. AB - To investigate the basis of ambiguous reports of the validity and utility of processed electroencephalogram (EEG) detection of cerebral ischemia, 19 patients monitored during surgical procedures requiring clamping of the carotid artery were studied. The EEG was recorded and observed for detection of alteration of spectral edge frequency versus EEG power. Electrodes were positioned at the P3 C3' locations over the left hemisphere and P4-C4' areas over the right hemisphere (10-20 system of electrode placement). Maximum sensitivity was used for recordings of the processed EEG. Twelve of 19 patients had bilateral carotid vascular stenosis. Nine of 19 patients studied with EEG monitoring had EEG changes suggestive of cerebral ischemia during interruption of carotid artery blood flow by surgical manipulation, defined as a decline in EEG power of greater than 40% or a decline in spectral edge frequency of at least 3 Hz. Eight of these episodes occurred at the time of carotid vascular clamp placement. These changes were confirmed by the raw EEG. Whereas power band monitoring detected 9 episodes of suspected ischemia, alteration of spectral edge frequency was sufficient to detect only 2 of these episodes. One patient sustained a right hemispheric stroke detected intraoperatively by a 47% decline in EEG power; however, these changes were unaccompanied by intraoperative alteration of spectral edge frequency. It is concluded that monitoring of EEG power with processed EEG devices is a more sensitive indicator of cerebral ischemia than monitoring only the spectral edge frequency of the EEG. PMID- 1610994 TI - Effects of halothane and isoflurane on transient renal dysfunction associated with infrarenal aortic cross-clamping. AB - Aortic cross-clamping for reconstructive aortic surgery is associated with impairment of renal function. Halothane or isoflurane was used to assess the influence of volatile anesthesia on renal hemodynamics during aortic surgery. Nineteen patients with normal preoperative creatinine clearances who were scheduled for reconstructive aortic surgery were randomly divided into two groups: halothane group (n = 9) and isoflurane group (n = 10). Induction of anesthesia consisted of midazolam, fentanyl, and pancuronium. Anesthesia was maintained with fentanyl and halothane or isoflurane in nitrous oxide and oxygen (50/50). Systemic hemodynamics were similar in both groups throughout surgery. Before aortic cross-clamping, effective renal plasma flow (ERPF) (131I-hippuran clearance) and glomerular filtration rate (GFR) (99Tc-DTPA clearance) were significantly lower in the halothane group (118.4 +/- 25.6 and 19.7 +/- 5.2 mL/min, respectively) than in the isoflurane group (253.4 +/- 51.5 and 44.9 +/- 8.4 mL/min) (P less than 0.05 for both). During cross-clamping, the renal variables were not markedly affected in either group and remained higher in the isoflurane-anesthetized patients (232.9 +/- 47.1 and 49.5 +/- 1.2 mL/min for ERPF and GFR, respectively) than in the halothane-anesthetized patients (132.4 +/- 31.6 and 14.8 +/- 3.7 mL/min, respectively) (P less than 0.05). After aortic unclamping, ERPF increased markedly in both groups (467.8 +/- 122 and 362.5 +/- 57.7 mL/min in the halothane and isoflurane groups, respectively), as did GFR (74.8 +/- 22 and 71.8 +/- 13.1 mL/min, respectively). These results suggest that anesthesia with halothane is associated with transient renal vasoconstriction during abdominal surgery. In contrast, aortic cross-clamping during isoflurane anesthesia was not associated with renal hemodynamic impairment. PMID- 1610995 TI - Renal function and cardiopulmonary bypass: effect of perfusion pressure. AB - Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified. PMID- 1610996 TI - Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pediatric patients undergoing cardiac surgery: Part I. AB - Changes induced by cardiopulmonary bypass (CPB) may markedly affect the pharmacokinetics of drugs. Therefore, the pharmacokinetics of alfentanil before and after CPB were compared in infants and children undergoing cardiac surgery, who had been anesthetized with nitrous oxide in oxygen and low inspiratory concentrations of halothane. Six infants and six children were investigated. Before CPB, alfentanil, 200 micrograms/kg, and after CPB, alfentanil, 80 micrograms/kg, was infused in 10 minutes. Arterial blood samples were obtained before and after CPB for determination of plasma alfentanil concentrations. Bi exponential functions were fitted to the plasma concentration-time data using weighted least-squares nonlinear regression analysis. A correction was made to account for the contribution of the first infusion to the plasma concentrations measured during and after the second infusion. Total sampling time before CPB (45 to 75 minutes) was too short to allow full characterization of the pharmacokinetics of alfentanil, but allowed estimation of the initial volume of distribution. The initial volume of distribution before CPB was smaller (68 +/- 37 mL/kg in infants and 80 +/- 32 mL/kg in children) than after CPB (235 +/- 58 mL/kg in infants and 179 +/- 99 mL/kg in children; P less than 0.001). The normalized area under the plasma concentration-time curve from 0 to 45 minutes was larger before CPB (17.9 +/- 2.9 mg.min/L in infants and 18.3 +/- 5.4 mg.min/L in children) than after CPB (11.1 +/- 2.9 mg.min/L in infants and 12.9 +/- 3.4 mg.min/L in children; P less than 0.001). Despite intravenous administration of atropine, arterial blood pressure and heart rate decreased significantly after alfentanil was given. PMID- 1610997 TI - Pharmacokinetics of alfentanil before and after cardiopulmonary bypass in pigs: Part II. AB - The pharmacokinetics of alfentanil before and after cardiopulmonary bypass (CPB) were investigated in six pigs undergoing mitral valve replacement. Before bypass, alfentanil, 100 micrograms/kg, was infused in 10 minutes and after bypass, alfentanil, 40 micrograms/kg, was infused in 10 minutes. Low inspiratory concentrations of halothane were given concomitantly. Arterial blood was obtained before and after CPB for determination of plasma alfentanil concentrations by gas chromatography. Bi-exponential functions were fitted to the plasma concentration time data using weighted least-squares nonlinear regression analysis. The steady state volume of distribution (Vss; 258 +/- 70 mL/kg), elimination clearance (Cle; 10.7 +/- 3.0 mL/kg/min), and distribution clearance (Cld; 6.8 +/- 3.3 mL/kg/min) before CPB were smaller than the Vss (1,107 +/- 373 mL/kg; P less than 0.01), Cle (20.0 +/- 3.0 mL/kg/min; P less than 0.002), and Cld (23.0 +/- 6.7 mL/kg/min; P less than 0.02) after CPB. The distribution half-life (t1/2 lambda 1; 2.8 +/- 0.8 minutes) was longer and the elimination half-life (t1/2 lambda 2; 36 +/- 8 minutes) was shorter before CPB than the t1/2 lambda 1 (1.7 +/- 0.2 minutes; P less than 0.05) and t1/2 lambda 2 (68 +/- 20 minutes; P less than 0.02) after CPB. PMID- 1610999 TI - Portable percutaneous cardiopulmonary bypass: use in supported coronary angioplasty, aortic valvuloplasty, and cardiac arrest. PMID- 1611000 TI - Unrecognized coronary ostial stenosis as a cause of postoperative cardiac mortality. PMID- 1610998 TI - The effect of administering or withholding dextrose in pre-bypass intravenous fluids on intraoperative blood glucose concentrations in infants undergoing hypothermic circulatory arrest. AB - Thirty-six fasted infants under 1 year of age who were scheduled for elective cardiac surgery using hypothermic bypass with circulatory arrest were randomized to receive a lactated Ringer's (LR) solution (group I) or a LR with 5% dextrose solution (group II) in the pre-bypass period. Marked increases in blood glucose concentrations were found following institution of bypass and circulatory arrest in the children in both groups. There was no correlation between the amount of dextrose infused in the pre-bypass period and the presence of hyperglycemia following institution of bypass. A single patient in group I was hypoglycemic (blood glucose less than 30 mg/dL) on the initial glucose determination and the blood glucose did not increase during the pre-bypass period. Elimination of dextrose from the parenteral fluids given before bypass will not eliminate hyperglycemia following institution of bypass; however, it may expose pediatric patients to the risks of hypoglycemia before bypass. PMID- 1611001 TI - Management of a difficult intubation during acute myocardial ischemia following a failed angioplasty. PMID- 1611002 TI - Tension pneumothorax following interpleural catheterization during positive pressure ventilation. PMID- 1611003 TI - Case 3--1992. General anesthesia complicated by unexpected hypertension and tachycardia. PMID- 1611004 TI - Pro: cerebrospinal fluid drainage prevents paraplegia. PMID- 1611005 TI - Con: cerebrospinal fluid drainage does not afford spinal cord protection during resection of thoracic aneurysms. PMID- 1611006 TI - Intrapulmonary Doppler for continuous measurement of cardiac output. PMID- 1611007 TI - Peripheral intravenous catheterization: confirmation with echocardiography. PMID- 1611008 TI - An aid for percutaneous arterial catheterization in small children. PMID- 1611009 TI - Misleading capnography in primary pulmonary hypertension. PMID- 1611010 TI - Heart transplantation in a patient with central core disease. PMID- 1611011 TI - Annual scientific meeting of the Gastroenterological Society of Australia. Brisbane, Australia, 30 April-2 May 1992. Abstracts. PMID- 1611012 TI - Ascending infection of the biliary tract after surgical sphincterotomy and biliary stenting. AB - It has been widely accepted that there is an ascending route of bacterial infection of the biliary tract but there is a lack of direct evidence. This hypothesis was tested in an animal experiment using the cat as an animal model. The implantation of biliary stents and surgical sphincterotomy were performed in these animals, with sham controls. Stents bypassing the sphincter of Oddi with the tip in the duodenal micro-organisms and the biliary tract was heavily contaminated. Blockage of these stents resulted in biliary obstruction. Stents implanted within the common bile duct, proximal to the sphincter were largely unaffected by biofilm formation. After surgical sphincterotomy the biliary tract was also contaminated but, in the absence of obstruction, the animals did not develop any symptoms. It was concluded that ascending infection by duodenal biliary reflux, via the sphincter of Oddi, is an important route of infection in the biliary system. PMID- 1611013 TI - Lack of hepatic benefit by oxygen inhalation during vasopressin infusion in patients with cirrhosis. AB - Vasopressin has been found to impair hepatic function in patients with cirrhosis. The aim of this study was to investigate whether oxygen inhalation could improve hepatic function during vasopressin infusion. Vasopressin (0.3 iu/min) was infused into eight patients with cirrhosis for 50 min. During the first 30 min they were ventilated by room air and for the following 20 min by oxygen (approximate 50% of FiO2). The extra oxygen inhalation caused a typical increase in arterial (+7%, P less than 0.01), portal venous (+8%, P less than 0.05), and hepatic venous (+9%, P less than 0.01) oxygen content. No effect was noted in arterio-hepatic venous and portal venous-hepatic venous oxygen content difference in comparison with the values after vasopressin alone. The hepatic perfusion remained unchanged. These results suggest that the extra oxygen did not increase hepatic oxygen uptake. Similarly, intrinsic clearance of indocyanine green did not improve. It is concluded that oxygen supplement in this setting has no hepatic benefit in patients with cirrhosis. PMID- 1611014 TI - Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C. AB - Survival rates were calculated for 251 patients with cirrhosis of the liver but without hepatocellular carcinoma, primary biliary cirrhosis, or autoimmune cirrhosis who underwent laparoscopy during the past 21 years at the authors' hospital. The survival rates were calculated by the Kaplan-Meier method. Stored serum was assayed for hepatitis B surface antigen (HBsAg) and antibodies to the hepatitis C virus (HCV). Patients with alcoholic cirrhosis had significantly better survival rates than patients with HBsAg, HCV, or both. Differences in survival rates between patients with hepatitis B and C were insignificant. In both groups, habitual drinkers had a significantly lower survival rate. The results suggested that alcohol accelerates liver damage in subjects with viral hepatitis. PMID- 1611015 TI - Combination therapy with ursodeoxycholic acid and colchicine for primary biliary cirrhosis. AB - Twelve patients with primary biliary cirrhosis (PBC), stages I to III, received long-term therapy with a combination of 600 mg ursodeoxycholic acid (UDCA) and 1 mg colchicine given daily for more than 2 years. Drug toxicity was mild; one patient experienced diarrhoea that was probably due to colchicine. Serum levels of bilirubin, alkaline phosphatase (ALPase), gamma-glutamyl transpeptidase and alanine aminotransferase decreased by more than 50% of the initial values. Serum albumin and cholesterol levels also improved, but immunoglobulins and anti mitochondrial antibody titre did not change. Histologic features in the eight patients who received serial liver biopsies before and 2 years after the beginning of treatment were evaluated. Piecemeal necrosis and portal inflammation were improved, but there was no change in portal fibrosis. Patients were divided into two groups; the first received both drugs from the outset, and the second group were started on UDCA for 3 months followed by the addition of colchicine. After 3 months, the improvement in serum bilirubin and ALPase in the first group was greater than in the second. However, in the second group, the ALPase levels had decreased significantly when measured at 6 and 9 months after the treatment compared with the levels at 3 months. These findings suggest that UDCA and colchicine may have a synergistic effect. This combination therapy appears to be safe and effective, both clinically and histologically, for treating PBC. PMID- 1611016 TI - Enhanced vasoconstrictor response of the isolated perfused cirrhotic rat liver to humoral vasoconstrictor substances found in portal venous blood. AB - Humoral vasoconstrictor factors in portal venous blood have an important influence on hepatic vascular tone. The aim of this study was to determine whether there is altered reactivity of the intrahepatic portal vascular bed of cirrhotic livers to such factors. Isolated perfused rat liver preparations (IPRLP) obtained from rats with carbon tetrachloride-induced cirrhosis and from normal controls were treated with small aliquots of fresh, heparinized venous blood (4% vol/vol) added to a synthetic perfusate composed of 2.5% bovine serum albumin in Krebs-Henseleit buffer. Compared with blood from the inferior vena cava, portal venous blood produced a greater increase in perfusion resistance of normal IPRLP (2.8 +/- 0.7 vs 15 +/- 3%, P less than 0.05). There was no significant difference in the response of normal IPRLP to portal venous blood obtained from cirrhotic animals compared with portal blood from normal controls (10 +/- 4 vs 15 +/- 3%). However, cirrhotic IPRLP were significantly (P less than 0.05) more responsive to portal venous blood than were control livers, regardless of whether the blood was obtained from control (28 +/- 6%) or cirrhotic (24 +/- 6%) rats. The response of both control and cirrhotic IPRLP to portal blood could be partially inhibited by the alpha-adrenoceptor antagonist phentolamine (5 x 10( 6) mol/L) and cirrhotic IPRLP were more responsive than controls to exogenous noradrenaline (518 +/- 27 vs 363 +/- 21%, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611017 TI - Responses to cholecystokinin octapeptide in patients with functional abdominal pain syndromes. AB - Clues to the pathogenesis of functional pain syndromes may be derived from the study of stimuli that precipitate or aggravate symptoms. In this study, cholecystokinin octapeptide (CCK-8, 0.06 microgram/kg) and placebo were given by intravenous infusion (5 min) in random order to control subjects and four groups of patients with unexplained abdominal pain. Induction of pain and nausea were assessed by linear analogue scales while sympathoadrenomedullary responses were assessed by serial changes in plasma concentrations of noradrenaline, adrenaline and dopamine. Scores for pain and nausea were low after infusion of placebo. After infusion of CCK-8, pain scores were significantly higher in patients with spontaneous pain than in control subjects, but significant increases in nausea were restricted to patients with irritable bowel syndrome and a subgroup of patients with pain after cholecystectomy. Although some groups showed increases in plasma concentrations of catecholamines after the infusion of CCK-8, the size of these increases was neither consistent among patients within each group nor predictive of scores of pain and nausea in individual subjects. Pain during the infusion of CCK-8 was a feature common to patients with diverse functional pain syndromes, and did not appear to be attributable to activation of the sympathetic nervous system. PMID- 1611019 TI - Gastric mucosal barrier: intergranular matrix of gastric surfactant in the mucous lining. AB - Transmission electron microscopy of rat gastric mucosa fixed by a novel procedure designed for barriers to water-soluble solutes has shown that the intergranular matrix material of gastric mucus is oligolamellar surface-active phospholipid. It is a gastric surfactant similar to that seen on deeper mucus-free surfaces also exposed to acid. PMID- 1611018 TI - Peptic ulcers and abdominal aortic aneurysms. AB - Upper gastrointestinal endoscopy was performed in 106 of 204 Chinese patients with intact abdominal aortic aneurysms, ninety-seven for screening and nine for gastrointestinal bleeding or pain. Peptic disease was discovered in 38 patients: 12 duodenal ulcers, 12 gastric ulcers, four duodenal and gastric ulcers, three duodenitis, three gastritis and four previously operated for ulcers. The eight patients who bled before aneurysmectomy all had gastric ulcers; four required emergency operation and two died. Only two patients bled from duodenal ulcers, both after aneurysmectomy and one died. Excluding gastritis and duodenitis, peptic ulcer was found in 26.4% of patients with abdominal aortic aneurysms. Half of these ulcers were gastric ulcers and 50% of them bled before aneurysmectomy. Duodenal ulcers tend to remain asymptomatic before operation and two of 12 (16.7%) bled postoperatively. The risk of bleeding for ulcers associated with aneurysms was 10 of 28 (35.7%) ulcers. The result of this uncontrolled study suggests that routine endoscopic screening should be used in all patients with aortic aneurysms and early surgery should be offered for gastric ulcers. PMID- 1611020 TI - Diabetes mellitus and operated peptic ulcer disease. AB - There is some evidence of an antagonism between peptic ulcer and diabetes mellitus. This antagonism is possibly related to anomalous insulin metabolism in duodenal ulcer patients. To evaluate this issue, 471 Rochester, Minnesota residents who had surgery for peptic ulcer were examined and then followed for up to 34 years. Their experience of diabetes mellitus was compared with that of Rochester residents generally, for whom data on diabetes incidence and prevalence were available. At surgery, the prevalence of diabetes was somewhat increased for gastric and slightly diminished for duodenal ulcer patients. Of the 445 patients who were free of diabetes at surgery, 27 developed it. By 20 years, the cumulative incidence of diabetes (9.1%) was less than expected (10.3%), but over the 20 years the difference was not significant for either gastric or duodenal ulcer patients. The risk of diabetes was not influenced by age, gender, or smoking status but analysis for relative weight at surgery indicated that obese patients had a 2.6-fold increase in risk of subsequent diabetes, whereas those with less than 1.2 relative weight had reduced risk. Relative weight was the only significant predictor of the time to subsequent diabetes in a proportional hazards regression analysis. The proposition of an antagonism between peptic ulcer and diabetes is not supported by the data. PMID- 1611021 TI - Modulation of the liver in cholestasis. PMID- 1611022 TI - Endoscopic management of bile duct stones. AB - The surgical risk of common duct exploration for the treatment of biliary calculi is considerably higher than that of cholecystectomy. Therefore, introduction of endoscopic sphincterotomy in 1974 was a major advance. It has become the therapy of choice in cholecystectomized patients or in those with an increased operative risk. Endoscopic sphincterotomy has a mortality rate of around 1% and a morbidity rate of 7%. These figures compare favourably with open surgery, especially in old patients. The procedure fails in about 10% of all patients referred for endoscopic removal of their calculi. However, several techniques have been described or are currently under evaluation to overcome these failures: intracorporeal or extracorporeal lithotripsy, long-term stenting of the bile duct, or direct application of solvents. Long-term follow-up studies show that between 2% and 20% of successfully managed patients may develop recurrent stones, mainly caused by bile stasis and infection. Patients with a functioning gall bladder and no concomitant gall-bladder stones probably do not require cholecystectomy after successful endoscopic treatment of their choledochal stones. While endoscopic stone removal has replaced surgery in the elderly frail patients it has no major advantages in the young and fit patients, especially when the gall-bladder is still in situ. PMID- 1611023 TI - Choledocholithiasis treated by ethylenediaminetetraacetic acid infusion through an endoscopic nasobiliary catheter. AB - A 64 year old man was admitted to the National Cheng Kung University Hospital for obstructive jaundice. He had received cholecystectomy 5 years previously. Sonography revealed common bile duct stones. He was treated with endoscopic nasobiliary drainage (ENBD) for 5 days for concomitant cholangitis. The muddy pigment stones disappeared completely after 10 days of infusion of ethylenediaminetetraacetic acid (EDTA) via the ENBD tube. There were no adverse effects, and he was stone-free 4 months later. PMID- 1611024 TI - Chlormezanone-induced fulminant hepatitis in a pregnant woman: successful delivery and liver transplantation. AB - The case of a 29 year old woman affected by fulminant hepatitis during the third trimester of pregnancy, after a 3 week administration of chlormezanone is reported. Following induced Caesarean delivery, the patient underwent an orthotopic liver transplantation. The mother and her baby were in good condition 26 months after liver transplantation. In this case, chlormezanone was probably responsible for the fulminant hepatitis. PMID- 1611025 TI - ACh-induced long-lasting enhancement in excitability of the olfactory bulb. AB - This study tested whether acetylcholine (ACh) could induce long-term modifications in neuronal excitability in the main olfactory bulb (OB). In anaesthetized rats, perfusion in the region of the mitral cell body layer was done with a push-pull cannula and the neuronal excitability was appraised through evoked field potentials (EFPs) elicited by stimulation of the laternal olfactory tract. Application of ACh (1 mM) for 15 min following a 10 min period of infusion with picrotoxin (GABAA antagonist, 0.4 mM) induced a large enhancement in the antidromic response of output cells which lasted for several hours. This result suggests that the cholinergic projections from the basal forebrain could be involved in processes supporting durable changes in OB response to odours. PMID- 1611027 TI - Temporal correlates of information processing during visual short-term memory. AB - The question is raised whether the sequence of spikes of a cortical neuron, i.e. its spike train, is related to cognitive functions. Neuronal patterns of firing in the inferotemporal cortex of monkeys performing visual delayed-matching tasks showed that short-term memory was accompanied by decreased bursting and changes in the incidence of recurrent spike-interval patterns. The temporal structure of the spike train suggests an inverse relationship between the incidence of repeated patterns and the degree of selectivity of sustained firing frequency elicited by the memorandum (sample stimulus). PMID- 1611026 TI - Cloning of drebrin A and induction of neurite-like processes in drebrin transfected cells. AB - The developmentally-regulated neuron-specific protein, drebrin A, is expressed first at the time of outgrowth and maturation of dendrites, and is localized within dendrites of the adult brain. A cDNA clone of adult rat drebrin A was isolated and sequenced. There is no overall homology with other reported protein sequences except chicken drebrins. We constructed the expression vector MIW-DA containing the drebrin A cDNA. Transfection of nonneuronal cells with MIW-DA induced the formation of highly branched neurite-like cell processes. In these process-bearing transfectants, expressed debrin A is concentrated in submembraneous regions of the cell. Furthermore, actin concentration is higher in these cells than other fibroblasts. These results suggest a possible role of drebrin A in neurite outgrowth. PMID- 1611028 TI - Oscillatory neuronal activity related to visual short-term memory in monkey temporal pole. AB - The activity of single neurons was recorded extracellularly from the temporal pole of monkeys while they were performing a visual short-term memory task. Neurons in the ventral part of the temporal pole showed sustained firing during the memorization delay period of the task when the monkey was remembering particular visual stimuli. The presence and absence of the firing were correlated with the correct and incorrect performance of the task, respectively. The sustained firing showed oscillation. The data suggest that visual information was stored as sustained firing among certain group of neurons producing oscillations. PMID- 1611029 TI - Different roles of flocculus and ventral paraflocculus for oculomotor control in the primate. AB - Responses of Purkinje cells were compared in the monkey flocculus and ventral paraflocculus. During vestibuloocular reflex (VOR) eye movements, flocculus Purkinje cells exhibited simple spike modulation related to head velocity, while ventral paraflocculus Purkinje cells exhibited modulation with no such head velocity preference. During smooth tracking of a sinusoidally moving small target, ventral paraflocculus Purkinje cells exhibited simple spike modulation related to target velocity or position, while the flocculus Purkinje cells exhibited a smaller modulation with no such target preference. Visual suppression of the VOR enhanced the simple spike responses in the ventral paraflocculus, but not in the flocculus. These results suggest that the primate flocculus and the ventral paraflocculus control differentially VOR and smooth pursuit eye movements, respectively. PMID- 1611030 TI - Spontaneous saccades under different visual conditions in the pigeon. AB - Spontaneous saccades of both eyes were recorded in head-restrained pigeons placed in 6 different visual conditions (darkness and biocular, uniocular, frontal or lateral viewing). Most saccades (95%) were biocular and directed forward (around the beak axis) and backward (around the horizontal line). In the dark, the proportions of forward and backward saccades were different, they became symmetrical when the visual input involved either the left eye, the lateral fields or both eyes. This spatial reorganization could be mediated by one 'dominant' eye through the lateral and foveal vision. Although some biocular saccades were strictly convergent, divergent or conjugate, most of them showed a higher independence since they had different directions and amplitudes for each eye. PMID- 1611031 TI - Eicosanoids, but not tachykinins, excite C-fiber endings in rat sciatic nerve-end neuromas. AB - Normal nociceptors are sensitized by hyperalgesic mediators such as eicosanoids and tachykinins. The possibility that these mediators contribute to hyperalgesic pain associated with neural injury was investigated by examining their effects on the excitability of injured afferent nerve endings. In amounts that sensitize normal nociceptors and are hyperalgesic in normal skin, the eicosanoids prostaglandin I2 (PGI2), and 8(R),15(S)-dihydroxyicosatetraenoic acid (8(R),15(S) diHETE) both excited some C-fibers in chronic neuromas of rat sciatic nerve. In contrast, the selective tachykinin-receptor agonists septide and senktide did not excite C-fibers. None of the mediators affected A-fibers. We conclude that PGI2 and 8(R),15(S)-diHETE may contribute to post-injury pain and hyperalgesia by an action on injured afferent endings. PMID- 1611032 TI - Effect of angiotensin II and eledoisin on cholinergic neurons in rat hippocampus. AB - Angiotensin II and eledoisin modulate drinking behaviour in rats that is mediated by monoaminergic and cholinergic neurons. In the present study we have shown that combined intracerebroventricular injections of either 0.1 or 1.0 microgram doses of angiotensin and eledoisin resulted in a decrease of about 25-35% in activities of choline acetyltransferase, ATP-citrate lyase in the hippocampus. In addition, 1 microgram quantities of these peptides depressed activity of carnitine acetyltransferase but did not alter activity of acetylcholinesterase. On the other hand, the application of 0.1 microgram of angiotensin caused no change in activity of monoamine oxidase A, while 1.0 microgram dose brought about its 67% activation. Eledoisin abolished this effect of angiotensin II. These data provide evidence that angiotensin II and eledoisin evoke non related adaptive changes in cholinergic and monoaminergic neurons of the hippocampus. PMID- 1611034 TI - Antisense bFGF oligodeoxynucleotides inhibit DNA synthesis of rat astrocytes. AB - Basic fibroblast growth factor (bFGF) is a multifunctional protein that stimulates proliferation, migration and differentiation of various cell types of the mammalian brain. In rat astrocyte cell cultures bFGF stimulates DNA synthesis after exogenous addition. This article will focus on the endogenous pathway of bFGF in rat astrocytes in cell cultures. After a single administration of bFGF antisense phosphorothioate oligodeoxynucleotide (PTO) a significant inhibition of DNA synthesis was observed. A control oligodeoxynucleotide does not inhibit DNA synthesis, while specific antisense c-myc PTO did inhibit DNA synthesis. Addition of anti bFGF PTO suppresses the expression of bFGF protein in Western blot analysis. These results suggest that bFGF may be an endogenous growth signal in developing astrocytes. PMID- 1611033 TI - Catalytic properties of cholinesterases: importance of tyrosine 109 in Drosophila protein. AB - Tyrosine 109 in the acetylcholinesterase sequence of Drosophila melanogaster corresponds to an aspartate in vertebrate cholinesterases. Mutation of this amino acid to a glycine in the human butyrylcholinesterase gives rise to the 'atypic' phenotype characterized by a reduced activity for charged compounds. We investigated the importance of tyrosine 109 in the Drosophila sequence by in vitro mutagenesis and its expression in the Xenopus oocyte. We show here that tyrosine 109 contributes to the conformation of the active site and the charge of the residue at position 109 is important for catalytic properties. Sensitivity of the enzyme to organophosphorus and carbamate compounds is modified depending on residues present in position 109, therefore this amino acid is a potential site of resistance for insects to insecticides. PMID- 1611035 TI - Late consequences of cryogenic brain lesion in rat; an electrophysiological study. AB - The left somatosensory cortex of PVG/C rats was subjected to a transcranial cold lesion, spontaneous and evoked cortical activity was studied 2-3 weeks after the lesion. The spontaneous activity underwent a depression at the focus of the lesion. Close to the epicentre of the lesion, the amplitude of the potentials evoked by electrical stimulation of the contralateral whisker pad was considerably smaller than in the controls and an almost complete reduction of the initial positive phase was found. Perifocally, 3-4 mm from the epicentre, evoked potentials with enhanced amplitudes were recorded in all experiments. It seems that considerable damage took place at the epicentre of the lesion, while perifocally an excitatory (and/or inhibitory?) mechanism was activated. PMID- 1611036 TI - Central injection of 5-hydroxytryptamine reduces food intake in obese and lean mice. AB - The effects of intracerebroventricular (ICV) administration of 5 hydroxytryptamine creatinine sulphate complex (5-HT), 35-140 nmol, on food intake in genetically obese (ob/ob) and lean mice were investigated. 5-HT (70-140 nmol) decreased feeding in a dose-related manner on 1 h and 2 h postinjection measures. Intake in lean mice was reduced by over 70% of the control condition. Obese mice, however, demonstrated a reduced sensitivity to the anorectic effect of 5-HT, and reduced 1 h intake by only 40% of saline control. Although these results are consisted with a role for serotonin in the control of food intake in mice, the altered sensitivity of the ob/ob to serotonergic stimulation may result, in part, from an impaired satiety control mechanism in this mutant. PMID- 1611037 TI - A mathematical model for the self-organization of orientation columns in visual cortex. AB - The visual cortex contains regular arrangements of neurons responding to specific types of visual stimulation, such as ocular dominance columns and orientation columns. These columnar structures can be considered as the functional architecture for early visual information processing. The model of activity dependent self-organization reported here demonstrates that both response properties of neurons to visual stimulation and the related columnar organization can be reproduced based on the competition between ON- and OFF-center inputs. Furthermore, the relationships between anatomical neural organization and its physiological response properties are clarified. This model also predicts new columnar organization linking the symmetry of receptive fields, which has never been examined. A hypercolumn, composed of orientation columns and symmetry columns, is suggested to serve as a basis for the representation of visual information. PMID- 1611038 TI - Development of orientation columns via competition between ON- and OFF-center inputs. AB - Development of orientation-selective receptive fields in primary visual cortex of higher mammals can occur through activity-dependent competition between ON-center and OFF-center inputs. This competition yields orientation and spatial-frequency selective 'simple cells' if the dark activity of ON (or OFF)-center inputs is best correlated with that of other ON (or OFF)-center inputs at small retinotopic separations and with that of OFF (ON)-center inputs at larger separations. Features of cat and monkey cortical organization emerge, including continuous and periodic arrangement of preferred orientation across the cortex. A new feature, systematic variation of receptive field spatial phase, is predicted. Experimental tests of this hypothesis are proposed. PMID- 1611039 TI - Aniracetam improves radial maze performance in rats. AB - The memory enhancing effect of the pyrrolidinone derivative aniracetam was investigated in rats trained in a delayed-response task in an 8-arm radial maze. Oral administration of aniracetam (100, 200, 400, or 800 mg kg-1) 16 h and again 1 h prior to a first trial of exposure to a given configuration of 4 baited arms resulted in a significant improvement in performance during a second trial in the maze given 3 h later in which there was access to all 8 arms but only the other 4 arms were baited. The pattern of baited arms was varied daily. The performance enhancement was greatest for the highest doses. These results extend the demonstration of the cognition enhancing effects of aniracetam to a spatial memory task in rats. PMID- 1611040 TI - Neuromagnetic auditory evoked responses after a stroke in the right temporal lobe. AB - Auditory evoked magnetic fields were recorded with a 24-SQUID magnetometer on a patient with a vascular lesion in the right auditory cortex and its vicinity. The contralateral transient 100 ms response (N100m) was absent over the damaged side, with no recovery within 16 months. Responses were normal over the healthy side. The responses to a binaural click train where interaural delays caused the perception of a shifting sound source; responses were again normal over the left side. Ipsilateral tones elicited N100m over the normal hemisphere but with smaller amplitude and longer latency than in healthy subjects. We suggest that ipsilateral responses are triggered by ipsilateral afferents but are significantly modified by excitatory callosal connections which did not work in our patient. PMID- 1611041 TI - Gaze holding defect induced by injections of ketamine in the cat brainstem. AB - The signal responsible for horizontal gaze holding is known to be generated, at least in part, by the prepositus hypoglossi (PH) nucleus, whereas that responsible for vertical gaze holding is known to be generated by the interstitial nucleus of Cajal (INC). An intramuscular injection of ketamine was recently demonstrated to induce a gaze holding failure. The aim of the present study was to analyse if ketamine produced this effect by acting, at least in part, on the PH nucleus. We found that a unilateral injection of a small amount of ketamine in the PH nucleus could cause either bilateral horizontal gaze holding failure or a vertical gaze holding failure or both an horizontal and a vertical gaze holding failure. PMID- 1611042 TI - Signal transduction and regulation of translation initiation. AB - Regulation of the rate of protein synthesis is important in the control of cellular proliferation. Changes in the rate of protein translation are brought about primarily at the level of initiation, which is usually rate limiting. This regulation involves the reversible phosphorylation of key initiation factors. Translation initiation factors eIF-4F, eIF-4B, and ribosomal protein S6 are phosphorylated in response to a wide variety of mitogens, growth factors, and tyrosine kinase oncogenes. Thus, translation initiation factors are important components of signal transduction pathways activated by extracellular factors and oncogenes. Of particular interest is the messenger RNA 5' cap-binding protein, eIF-4E. Overexpression of eIF-4E in fibroblasts results in malignant transformation, suggesting that it is an important transducer of growth signals, and that aberrant expression of a translation factor can cause malignancy. Elucidation of the components of the signalling pathways which regulate initiation factor activity should increase our understanding of how extracellular factors and oncogenes effect cellular proliferation, and the role that translation plays in this process. PMID- 1611043 TI - Proto-oncogenes in the regulatory circuit for myogenesis. AB - Skeletal muscle cells have provided an auspicious system for dissecting the mechanisms through which growth factor signals disrupt programs for cellular differentiation. Insight into the molecular mechanisms that control muscle differentiation has recently been obtained through the cloning of a family of muscle-specific transcription factors, often referred to as the MyoD family, that can activate myogenesis. The expression and activity of these factors are negatively regulated by growth factor signals and by activated oncogenes whose products transduce growth signals from the cell membrane to the nucleus. This review will focus on the role of proto-oncogenes in the transduction of growth factor signals that regulate myogenesis and on the cross-talk between the regulatory circuits that control myoblast proliferation and differentiation. PMID- 1611044 TI - Use of transgenic mice in the study of proto-oncogene functions. AB - The introduction of genes into the germ line of mammals has been utilized to study the regulation of gene expression, the role of certain genes during development and to establish animal models of human diseases. The present report explores the application of transgenic mice methodology to the study of the normal and transforming activity of some proto-oncogenes in the living animal. The major findings of these studies and their contribution to our understanding of the role of these proto-oncogenes in development and transformation will be evaluated. PMID- 1611045 TI - Mechanisms of signal transduction by Ras. AB - The role of Ras in the transduction of signals that control cell growth is undisputed. However, the identity of the Ras signalling pathway remains unknown. Evidence is mounting that Ras can receive signals from different cell surface receptors most likely via a common intermediate, GAP. A new insight into the possible function of Ras is provided by the recent findings that certain ligands can induce the coordinated redistribution of Ras and cell surface receptors. The next challenge is to identify the specific targets for the action of Ras. PMID- 1611046 TI - [Met-enkephalin restores self-stimulation behavior in rabbits after destruction of the hypothalamic nuclei]. AB - Contralateral lesions of ventromedial and lateral hypothalamic nuclei inhibited hypothalamic self-stimulation in rabbits. Intracerebroventricular injection of metenkephalin evoked the restoration of self-stimulation behavior. PMID- 1611047 TI - [Role of initial hemodynamic status and rate of blood loss replacement in postresuscitation changes in blood circulation and animal mortality]. AB - In 43 experiments performed on narcotized dogs after 10 min clinical death induced by exsanguination, the peculiarities of postresuscitation changes in the blood circulation associated with the initial hemodynamic status, the rate of the blood loss replacements after restoration of cardiac activity, and the use of infusion therapy by albosorb (specifically processed albumin) were studied. The effect of the initial level of stroke index (SI) on the pronouncement of postresuscitation derangements in the central hemodynamics (CHD) and on the resuscitation outcome was determined. With the initial value of SI being mean, the maintenance of a moderate blood deficit (10 to 15 ml/kg) within the first hour of restoration was accompanied by an improvement in the survival rate of the animals as compared with a rapid and complete replacement of the blood. The infusion of albumin and creation of a moderate overtransfusion by the first hour post resuscitation removed the prognostic value of the initial SI. PMID- 1611048 TI - [Study of humoral hemolytic factors in hemorrhage using chromatographic methods]. AB - The kidney-dependent increase of the haemolytic activity of blood serum after acute decompensated blood loss was demonstrated in the experiments on rats. The preparative ion-exchange chromatography on DEAE-Toyoperal was used to separate the haemolytic active component of the posthaemorrhagic blood serum with the max value of the specific activity of 6.86 A/micrograms protein. The analysis of the separated component by size-exclusion chromatography on TSK-G3000-SW column indicated a molecular mass of 80-100 kDa. In injection in the circulatory system in in vivo experiments the dose-dependent effect of the action of separated component was demonstrated. PMID- 1611049 TI - [Daily dynamics of iron excretion with murine in experimental hepatosis]. AB - Experimental hepatosis induced by intragastric administration of CCl4 was revealed to be accompanied by changes in temporal organization of lipid peroxidation, sideremia and iron excretion with urine. Even at early stages of organ lesions, the activation of free-radical lipid oxidation and rearrangement of sideruria circadian rhythm were found to result in a substantial and stable increase in mesor of the trace element excretion with urine in spite of a statistically significant decrease in water release. PMID- 1611050 TI - [Features of gastrin reaction in rats with different susceptibilities to gastric mucosa lesions in immobilization-cold stress]. AB - The connection between the character of gastrin and acid reactions and visible morphological changes of gastric mucosa in immobilising-cold stress was studied in the experiments on mongrel rats. It is established that in the rats the fundal gastric mucosa is resistant to the disturbing action of the immobilising-cold stress. The post-stress gastrin contents in the antrum and duodenum mucosa is higher and in the serum lower than in rats with ulceration. The rats with the stress erosions have the intermediate position. The acid factor didn't play the significant role in the ulcerogenesis because its value didn't overstep the limits established in the extradigestive period. PMID- 1611051 TI - [Activation of lipid peroxidation and changes in vitamin E contents in the lungs under oxidative stress]. AB - The lipid peroxidation (LPO) of the lung tissue and the bronchoalveolar lavage in rats under the influence of immobilization has been investigated. The effects accompanying the development of oxidative stress in animals--an increase in the content of conjugated dienes and fluorescent LPO products in biological objects and a strong decrease in the content of vitamin E in the lung tissue were registered. PMID- 1611052 TI - [Contents of prostaglandins F2alpha, I2 (prostacyclin) and thromboxane A2 in the dog liver during development of hemorrhagic shock]. AB - Contents of prostaglandins (PGs) F2 alpha, I2 and thromboxane (TH) A2 in the liver of 6 dogs has been studied in dynamics of hemorrhagic shock development. The results show that acute haemorrhage (31.9 +/- 1.6 ml/kg) stimulates the synthesis and release of all the eicosanoids studied. Nevertheless, in the progression of shock a significant difference was noticed between the high TXA2 and PGF2 alpha rates and comparatively lower rise of PGI2 production. The late stage of shock (201 +/- 44 minutes after haemorrhage) was characterized by a further rise in TXA2 and PGF2 alpha rates with simultaneous lowering of PGI2 as a result of vascular endothelium affection which is the main source for prostacyclin synthesis. In view of the antagonism of PGI2 to TXA2 and PGF2 alpha and its cytoprotective effects, the results of present investigation give the experimental background for using prostacyclin or its synthetic analogues in a complex therapy of acute liver failure in clinic. PMID- 1611053 TI - [Modification of radiation sensitivity of lymphocytes of the rat thymus gland using cholesterol-enriched autoliposomes]. AB - The influence of thymocyte enrichment with cholesterol on radiosensitivity of these cells has been studied. The enrichment was performed using autoliposomes. It was found that in the modified cells the processes of lipid peroxidation, enzymatic degradation of chromatin and apoptosis are inhibited. PMID- 1611054 TI - [Xanthine oxidase activity in mononuclear cells of human blood]. AB - Xanthine oxidase activity has been revealed in human blood mononuclear cells. The enzyme is found in these cells only after solubilization. This may become the explanation for contradiction with other previous data claiming absence of xanthine oxidase in human blood mononuclears. The level of enzyme activity is 2.76 +/- 0.029 mu mol/g protein.min. The latter is readily inhibited with allopurinol and folic acid. PMID- 1611055 TI - [Effects of antioxidant emoxipin on lipid metabolism in the lungs during development of pulmonary edema]. AB - Trials in white rats have shown, that intravenous injection of pituitrin (10 U/kg), challenging marked pulmonary edema, resulted in decrease of general lipids in them, as well as cholesterol, phospholipids and free fatty acids with accumulation of lipid peroxidation (LP) products. Preliminary administration of antioxidant emoxipin prevented the decrease in the level of general lipids, phospholipids and fatty acids, promoted a further decrease in cholesterol concentration in them and strongly inhibited lipid peroxidation processes. All this was combined with the development of more pronounced pulmonary edema. Intratracheal administration of a strong inductor of LP--Butyl hydroperoxide has never resulted in the development of pulmonary edema in white rats. These and earlier obtained data ground the statement, that LP--products are not pathogenic in the development of pulmonary edema. Inhibition of their formation may increase its development due to intensification of the signal from the receptor towards intracellular effector systems. PMID- 1611056 TI - [Rabbit liver secretes oxidated lipoproteins in experimental atherosclerosis]. AB - It is shown in rabbits, that alimentary hypercholesterolemia proceeds with increasing lipid peroxidation in liver homogenate, blood serum and apo-B containing lipoproteins. It is established in the model of liver perfusion in rabbits, that liver cells produce apo-B-containing level of lipid peroxidation. The lipid peroxidation increases in perfusate and in the fraction of lipoproteins (d less than 1,065 g/cm3) from this perfusate. Lipid peroxidation can interfere in the changing of physicochemical characteristics of lipoproteins at the stage of synthesis and secretion of lipoproteins by liver cells. PMID- 1611057 TI - [Mechanism of the action of ultraviolet irradiation of blood on the organism of experimental animals]. PMID- 1611058 TI - [Differences in mechanisms of action of beta-acetyldigoxin, strophanthin K and ouabain]. AB - In vitro on skinned myocardial fibers (SMF) with extracted or functionally inactivated enzymes and membranes of mitochondria, longitudinal sarcoplasmic reticulum, triads and sarcolemma, new evidence of beta-acetyldigoxin and strophanthin K direct stimulating effects on contractile protein system of myocardium has been obtained. It has been revealed in energy release stimulation and force generation, in quantitative (beta-acetyldigoxin) or quantitative and qualitative (strophanthin K) stimulation of energy transduction, in the increase of contractile process cooperativity and Ca-sensitivity of SMF as well as in the SMF relaxation time extension (in the case of strophanthin K). It is suggested that different effects of beta-acetyldigoxin and strophanthin K are due to the differences in the conformations of actomyosin ensembles formed by strong bound (AMESB), which are induced by the influence of these cardiac glycosides. It has been demonstrated that ouabain (strophanthin K) has no direct effect on functioning of AMESB. PMID- 1611059 TI - [Effects of amiridin and tacrine, drugs effective in Alzheimer's disease, on the activity of monoamine oxidase A and B]. AB - In vitro comparative studies of effects of amiridin (9-amino-2, 3, 5, 6, 7, 8 hexahydro-1H-cyclopentane (b) choline monohydrate hydrochloride) and tacrine physostigmine and piracetam on monoamine oxidase A (MAO-A) and B (MAO-B) activity in the rat brain were carried out. Piracetam (1 x 10(-4)-1 x 10(-3) M) dose dependently increased MAO-A and MAO-B activity. At all concentrations used (1 x 10(-7)-5 x 10(-4) M) physostigmine had no effect on MAO-A and MAO-B activity. Amiridin was found to inhibit MAO-B activity at 5 x 10(-4) M concentration only. Tacrine inhibited MAO-A activity at 5 x 10(-4) M concentration. The therapeutical effects of amiridin and tacrine in treatment of Alzheimer disease were not related to their action on MAO-A and -B activity. PMID- 1611060 TI - [Antagonistic properties of tetra-substituted analog of vasopressin with selective antidiuretic effects]. AB - Biological properties of a novel vasopressin analogue were investigated. It was found that this analogue has no vasopressor and oxytocic activities but it exhibits a selective antidiuretic effect which is weaker than that of adiuretin (DDAVP). Novel analogue inhibits vasopressor, oxytocic and antidiuretic effects caused by arginine--vasopressin. The usefulness of novel compound as a pharmacological tool--vasopressin antagonist is suggested. PMID- 1611061 TI - [Effects of lithium hydroxybutyrate on circadian rhythm of rest-activity and sleep structure in experimental animals]. AB - Lithium hydroxybutyrate (10 mg/kg, 10 days) influences circadian temperature and activity rhythms of rats in "open field" and sleep structure according to the time of preparation of the injection (8.30 or 19.30). It was stated that lithium hydroxybutyrate modified circadian rhythms and sleep structure less after morning injections into the rats, while evening administration destabilized circadian rhythms, increased slow-sleep and decreased REM sleep duration. PMID- 1611063 TI - [Formation of stable chloramine complex in interactions of carnosine and hypochlorite anion]. AB - Nowadays carnosine is considered as a promising drug for different diseases. However, mechanism of its action has not been found yet. The study evaluated the interaction between carnosine and sodium hypochlorite. It is established that this reaction yields a stable chloramine complex which is likely to underlie the effect of the drug in cataracts. PMID- 1611062 TI - [Anti-ischemic protection of the brain using water-soluble form of aspirin acelisin]. AB - The domestic water-soluble aspirin (acelisin) has been used as an anti-ischemic brain protector. The total brain ischemia has been implemented in accordance with an original technique for 17 to 35 min. The doses of acelisin from 25 to 250 mg/kg have been tested during experiments. The infusion of solutions has been carried out before ischemia, 15 min before reperfusion and just after the beginning of reperfusion. The functional status and survival of rats have been evaluated during a week. The best result has been reached with 150 mg/kg acelisin injected 30 min before ischaemia. A positive effect was reported when acelisin was used in early postischaemic period. PMID- 1611064 TI - [Prenatal moderate effects of alcohol on ultrastructure of cortical capillaries in the offspring]. AB - Sensorimotor cortex of rat 21- and 30-day-old offspring given prenatally moderate alcohol doses revealed signs of hemodynamic, ultrastructural capillary and compensatory-adaptive changes. The 60-day-old offspring displayed the tendency to hemodynamic and ultrastructural reversibility in remaining edema of the pericapillary processes of astrocytes. It is suggested that the deficiency of cerebral circulation is a delayed aftereffect of prenatal brain hypoxia. Under alcohol intoxication before pregnancy the edema was not observed. There was polymorphism of ultrastructure of cortical capillaries and immature vessels in the offspring. PMID- 1611065 TI - [Levamin and cerebrolysin as immunostimulants]. AB - The experiments on mice have shown that the in vitro treatment of mouse bone marrow cells with levamin or cerebrolysin (amino acids mixture) increased the number of Thy-1 positive cells and stimulated the in vivo immune response to SRBC. Levamin proved more active. At the same time levamin and cerebrolysin had no effect on the immune response to thymus-independent Vi-antigen. PMID- 1611066 TI - [Role of immune complexes in thyroid diseases]. AB - To elucidate the immune complex (thyroglobulin-antibody, Tg-Ab) role in thyroid hormone formation, in vitro iodination of Tg--AB immune complex, bovine intact Tg and that of the patient with euthyroid goiter and partially purified AB to Tg were studied. We compared the amount of iodamine acids (MIT, DIT, T4/mole of Tg) forming during iodination in immune complex with other samples. The results suggest that Tg being in complex with antibodies (up to 30-40 mole of antibodies/mole of Tg) is iodinated forming the enough amount of MIT, decreased amount of DIT and T4. A MIT fraction increase is connected with additional iodination of complex antibodies. We suggest that such processes may take place in the patient body and be involved in pathogenesis of thyroid disease. PMID- 1611067 TI - [Effects of B-lymphocytes from different organs on hemopoietic colony formation in the spleen by bone marrow cells]. AB - The influence of B-lymphocytes from various sources on splenic colony formation was studied in the syngeneic system. B-lymphocytes were obtained by panning with IgG-fraction of rabbit anti-mouse Ig, absorbed on Petri dishes. In addition, adherent cells, Thy-1+ and SC-1+ were eliminated from the fraction of Ig(+) cells. SC-1- and SC-1+ fractions, containing, respectively, stem cells and T lymphocyte precursors, were obtained by panning with IgG-fraction of rabbit anti SC-1 serum. SC-1- cells transferred to irradiated syngeneic mice did not induce colony formation in the spleen. Introduction of SC-1- and SC-1+ cells induced formation of colonies. A similar helper effect occurred when SC-1(-)-cells were introduced with bone marrow or lymph node B-cells, but not with splenic B-cells. Splenic, but not bone marrow and lymph node B-cells inhibited colony formation by combination of SC-1- and SC-1+ cells. All effects of Ig+ cells were abolished by treatment of cells with rabbit anti-MBLA serum. Thus, B-cells of various origin can either enhance or inhibit colony formation. The enhancing of inhibitory effect after B (MBLA+)-cells elimination from suspension of bone marrow and lymph node (but not spleen) Ig(+)-cells resulted from the activity of B contrasuppressors. PMID- 1611069 TI - [Effects of ultraviolet irradiation of blood on immunity in experimental animals]. PMID- 1611068 TI - [Regulatory properties of the rat heart adenylate cyclase in the course of toxic infective shock caused by Yersinia pestis]. AB - Influence of intravenously administered to rats murine toxin of Y. pestis in the dose of I mg/ml (LD100) on the regulatory properties of heart plasma membranes adenylate cyclase (AC) has been studied during the intoxication. It has been shown that basal, fluoride,- and 5-guanylyl imidodiphosphate-stimulated AC activity remained unchanged during the intoxication. Stimulation of AC by isoproterenol, glucagon and histamine did not change during the first two hours and significantly decreased after 5 hours of intoxication. Affinity of AC for the investigated hormones did not change through the experiments. PMID- 1611070 TI - [Disorders of antithrombogenic activity of vascular walls in malignancy]. PMID- 1611072 TI - [Contents of extracellular DNA in blood of irradiated rats]. AB - Intact rat plasma contains high-molecular DNA which moves as a single fraction in 0.5% agarose electrophoresis. As early as 2-5 hours after gamma-irradiation in a dose of 1-100 Gy there appears low-molecular DNA (about 180 nucleotide pairs), the amount of which directly correlates with the irradiation dose 5 hours after the exposure. Blot-hybridization showed that low-molecular DNA has no common nucleotide sequences with high-molecular DNA, though has sites similar to genome repeat sequences. PMID- 1611071 TI - [Formation of specific antitumor cytotoxic T-lymphocytes in monoculture]. AB - A new model for the generation of specific antitumor cytotoxic T-lymphocytes (CTL) was proposed. In contrast to other models, it allows to generate effector CTL without immunization in vitro. C57BL/10 mice or/and C57BL/6 mice were immunized by injection with gamma-irradiated syngeneic tumor cells into the footpads. For estimation of cytotoxic activity, chromium-51 release assay was used. It has been shown that effector CTL were absent in the lymph nodes in 1 fold as well as 2-fold immunization. Cytotoxic cells have not been found in 1 fold immunization even after maturation of the lymphocytes in monoculture. Specific CTL were detected only after secondary immunization and subsequent cultivation in vitro. Effector cells had Thy1.2+, Lyt2+, L3T4- phenotypes. Presence in vitro of exogenous IL-2 was needed for the generation of CTL against MX-11 sarcoma but not against EL4 lymphoma. We suggest that the release of IL-2 from lymphomas cells could stimulate generation of the effector cells through activation of the endogenous production of IL-2, or due to some other factors. PMID- 1611073 TI - [Effects of hepato-protective agents thioctacid and flavobion on histones in intact and regenerating liver of irradiated rats]. AB - The changes in concentration, total content of histones and relative proportion of individual histone fractions in intact and regenerating liver were followed in rats after administration of hepatoprotective agents flavobion and thioctacid and after whole-body gamma irradiation with a dose 5.7 Gy. We found that thioctacid alone caused an increase in histone concentration in intact liver whereas flavobion alone did not produce significant quantitative changes. Irradiation alone decreased markedly the concentration and total content of histones in intact as well as regenerating liver of unprotected rats. Administration of thioctacid or flavobion protected from these quantitative histone changes or alleviated them considerably. In relative proportion of individual histone fractions, the most profound changes were found in H1 histone after flavobion application. PMID- 1611074 TI - [Age-related characteristics of the effects of epithalamin on serotonin metabolism in the pineal gland of rats]. AB - The biosynthesis of serotonin into melatonin was decreased in old (18-20-month) in comparison to young (4-5-month) male Wistar rats. 5-day morning injections to young and old rats with polypeptide pineal preparation (epithalamin) in a dose of 2.5 mg/kg of body weight induced the increase in the night peak of serotonin, N acetylserotonin and melatonin in young and melatonin alone in old rats and did not influence 5-methoxytryptamine, 5-oxy- and 5-methoxyindoleacetic acids level. These data support suggestion of ultrashort loop between pineal peptides and indoles and that epithalamin increases the metabolism of serotonin into melatonin. PMID- 1611075 TI - [Structural-functional rearrangement in the thalamic relay nuclei during sensory deficit]. AB - Experiments in adult cats surviving five days, four months and one year after neurosurgical section of the optical tract, half of the midbrain tegmentum, show the stability of cytoarchitectonic organization of LGB and ventro-basal nuclear complex of the thalamus due to ultrastructural plastic rearrangement of the studied neural centers and alterations in the sensory system as a whole. PMID- 1611076 TI - [Morphometric evidence of activation of axo-somatic synapses during administration of delta sleep-inducing peptide]. AB - Computed morphometry proved activation of neocortex layer III-V axosomatic synapses. This is evident from an increase in the mean plasmalemma length, that in the active synapse zones on neurone bodies and width of the synaptic cleft, this being induced by a single intraperitoneal administration of delta-sleep inducing peptide. The activation of the axosomatic synapses correlates with elevated GABA levels in the cerebral hemispheres cortex. PMID- 1611077 TI - [Nuclear bodies in rat hepatocytes: dynamics of appearance and formation in aging and functional actions]. AB - Using electron microscopy, we studied the morphology of nuclear bodies (NB) in hepatocytes of rat Wistar males of various ages both in intact and upon single bleeding and enterosorption. NB are round formations 2-3 microns in size consisting of loosely packed up chromatin filaments with spherical formations (CFSF) 0.01 micron in size similar to those in prenucleosomal level of chromatin organization. NB are often detected in hepatocytes with the signs of intracellular hyperplasia, granular dystrophy and apoptosis. In intact rats NB are observed only in old rat hepatocytes (in 1-2 per 10 nuclei). Bleeding considerably increases their number and makes NB to appear in young animals. There are 4 stages of NB formation depending on the moment of blood letting: 1- free CFSF in nucleoplasma, 2--CFSF surrounded with a fibrillar zone along the periphery, 3--CFSF and partly condensed chromatin surrounded by a fibrillar zone, 4--completely condensed chromatin surrounded by a fibrillar zone. Enterosorption causes the appearance in old rat hepatocytes of NB at different stages, mainly at stage 4. The nature of NB is not clear, but they obviously reflect the modification in functional activity of relevant genome loci. PMID- 1611078 TI - Genetic alterations in leukemia: events on a grand scale. PMID- 1611079 TI - Shear stress-induced von Willebrand factor binding to platelet glycoprotein Ib initiates calcium influx associated with aggregation. AB - Platelets subjected to elevated levels of fluid shear stress in the absence of exogenous agonists will aggregate. Shear stress-induced aggregation requires von Willebrand factor (vWF) multimers, extracellular calcium (Ca2+), adenosine diphosphate (ADP), and platelet membrane glycoprotein (GP)Ib and GPIIb-IIIa. The sequence of interaction of vWF multimers with platelet surface receptors and the effect of these interactions on platelet activation have not been determined. To elucidate the mechanism of shear stress-induced platelet aggregation, suspensions of washed platelets were subjected to different levels of uniform shear stress (15 to 120 dyne/cm2) in an optically modified cone and plate viscometer. Cytoplasmic ionized calcium ([Ca2+]i) and aggregation of platelets were monitored simultaneously during the application of shear stress; [Ca2+]i was measured using indo-1 loaded platelets and aggregation was measured as changes in light transmission. Basal [Ca2+]i was approximately 60 to 100 nmol/L. An increase of [Ca2+]i (up to greater than 1,000 nmol/L) was accompanied by synchronous aggregation, and both responses were dependent on the shear force and the presence of vWF multimers. EGTA chelation of extracellular Ca2+ completely inhibited vWF-mediated [Ca2+]i and aggregation responses to shear stress. Aurin tricarboxylic acid, which blocks the GPIb recognition site on the vWF monomer, and 6D1, a monoclonal antibody to GPIb, also completely inhibited platelet responses to shear stress. The tetrapeptide RGDS and the monoclonal antibody 10E5, which inhibit vWF binding to GPIIb-IIIa, partially inhibited shear stress induced [Ca2+]i and aggregation responses. The combination of creatine phosphate/creatine phosphokinase, which converts ADP to adenosine triphosphate and blocks the effect of ADP released from stimulated platelets, inhibited shear stress-induced platelet aggregation without affecting the increase of [Ca2+]i. Neither the [Ca2+]i nor aggregation response to shear stress was inhibited by blocking platelet cyclooxygenase metabolism with acetylsalicylic acid. These results indicate that GPIb and extracellular Ca2+ are absolutely required for vWF mediated [Ca2+]i and aggregation responses to imposed shear stress, and that the interaction of vWF multimers with GPIIb-IIIa potentiates these responses. Shear stress-induced elevation of platelet [Ca2+]i, but not aggregation, is independent of the effects of release ADP, and both responses occur independently of platelet cyclooxygenase metabolism. These results suggest that shear stress induces the binding of vWF multimers to platelet GPIb and this vWF-GPIb interaction causes an increase of [Ca2+]i and platelet aggregation, both of which are potentiated by vWF binding to the platelet GPIIb-IIIa complex. PMID- 1611081 TI - Protein C deficiency Hong Kong 1 and 2: hereditary protein C deficiency caused by two mutant alleles, a 5-nucleotide deletion and a missense mutation. AB - We characterized a mutant protein C gene from an individual with no detectable protein C antigen in blood plasma. Southern blot hybridization analysis with human protein C cDNA demonstrated neither gross deletion nor rearrangement of the gene. Sequencing all the exons and exon-intron boundaries of the gene except the 3' noncoding region showed two mutant alleles. The one, derived from the mother, represents a deletion of 5 nucleotides (nt) (CCCGC) in the end of exon VI (mutation I), predicted to result in the generation of a new stop codon due to a reading frameshift and the premature termination of translation. The other, derived from the father, represents a point mutation (G to A) in exon IX (mutation II), resulting in an amino acid substitution, Gly-376(GGC) to Asp(GAC), in the catalytic domain of the protein. Allele-specific oligonucleotide probe hybridization confirmed the presence of the two mutations. Mutation I would result in a truncated polypeptide of 169 amino acid residues that lacks the heavy chain. Mutation II gives rise to an alteration of a highly conserved amino acid, Gly-376. These data indicate that this patient is a compound heterozygote of the two mutant alleles, each one inherited from each parent. Transient expression assays using COS-7 cells transfected with mutated protein C expression vectors suggested that each of the two mutations leads to the protein C deficiency by causing an impairment of secretion of the respective mutant proteins. PMID- 1611080 TI - Interleukin-4 suppresses plasminogen activator inhibitor-2 formation in stimulated human monocytes. AB - Using a specific enzyme-linked immunosorbent assay, plasminogen activator inhibitor-2 (PAI-2) was quantitated in cultures of human monocytes. Lipopolysaccharide (LPS) increased both extracellular and cell-associated PAI-2 levels, as well as PAI-2 mRNA measured by Northern analysis. Both the lymphokine, interleukin-4 (IL-4) (greater than or equal to 10 pmol/L), and the glucocorticoid, dexamethasone (100 nmol/L), inhibited PAI-2 formation and PAI-2 mRNA induction. Another lymphokine, interferon-gamma (IFN-gamma) (100 U/mL), as for IL-4 alone, did not stimulate PAI-2 formation; however, in contrast to IL-4, IFN-gamma did not reverse the LPS effect but could potentiate it. The suppression of PAI-2 formation by IL-4 and glucocorticoid in stimulated human monocytes extends the list of monocyte products whose synthesis can be downregulated in these cells by the two agents. The findings could have relevance to the control by monocytes/macrophages of connective tissue resorption, including that of fibrin, at sites of inflammation. PMID- 1611082 TI - Tumor necrosis factor-alpha modulation of glycoprotein Ib alpha expression in human endothelial and erythroleukemia cells. AB - Glycoprotein Ib alpha (GpIb alpha) is a platelet membrane Gp that binds von Willebrand factor and mediates platelet adhesion to subendothelium. We have found both GpIb alpha mRNA and protein in human umbilical vein endothelial cells (HUVEC). In previously published work we reported that combined treatment with interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) markedly increased the GpIb alpha mRNA level in HUVEC. We have now documented that TNF alpha alone induces GpIb alpha mRNA and protein expression, studied the kinetics of this response, and investigated potential mechanisms of the TNF-alpha effect. GpIb alpha mRNA induction by TNF-alpha is detectable as early as 2 hours after exposure to this cytokine, and reaches a maximal level after 20 to 24 hours. Using a nuclear run-on assay we found that GpIb alpha gene transcription is increased approximately 10-fold after 2 hours of TNF-alpha treatment. Furthermore, using two monoclonal antibodies that recognize different epitopes of GpIb alpha, we found that the protein expression in endothelial cells is markedly increased by TNF-alpha. Interleukin-1 (IL-1) and the phorbol ester phorbol myristate acetate, which mimic many effects of TNF-alpha on endothelial cells, have no effect on endothelial or human erytholeukemia (HEL)-cell GpIb alpha mRNA. TNF-alpha treatment for 24 hours increases the HEL cell GpIb alpha mRNA level approximately fourfold, showing a time- and dose-dependent effect similar to that seen in HUVEC. TNF-alpha-induced GpIb alpha mRNA and protein synthesis may play a role in mediating platelet or other cell interaction with activated endothelium. Unlike other endothelial pro-thrombotic and pro-adhesive proteins induced by TNF alpha, GpIb alpha is not induced by IL-1 treatment, which suggests a novel pathway for induction of this protein. PMID- 1611083 TI - Presence of cross-reactive antibody between human immunodeficiency virus (HIV) and platelet glycoproteins in HIV-related immune thrombocytopenic purpura. AB - We previously reported the presence in platelet eluates of autoantibodies directed against epitopes of the platelet glycoprotein (GP)IIb/IIIa complex in acquired immunodeficiency syndrome (AIDS)-free human immunodeficiency virus (HIV) infected patients with immunologic thrombocytopenic purpura (ITP). We investigated whether HIV antibodies recognized platelet membrane antigens to determine whether the virus might be directly or indirectly responsible for the thrombocytopenia in this context. Direct eluates of platelets from 25 patients with HIV-related ITP contained IgG reacting with HIV-GP160/120 and also, in 45% of patients, detectable antiplatelet antibodies, immunochemically characterized as anti-GPIIb and/or anti-GPIIIa in 5 patients. Furthermore, serum HIV-GP160/120 antibodies could be absorbed on and eluted from platelets from normal non-HIV infected healthy blood donors (indirect eluates). In contrast, GP160/120 antibodies present in the serum of nonthrombocytopenic HIV-infected patients were not absorbable on normal platelets in most patients, suggesting a pathogenic role in HIV-related ITP. We performed detailed studies of a patient with the highest titer of both HIV-GP160/120 and GPIIb/IIIa antibodies in direct and indirect platelet eluates. No antibody binding to GPIIb/IIIa-deficient Glanzmann thrombasthenic platelets was detected. Furthermore, binding/elution experiments conducted with insoluble recombinant GP160 (expressed in baculovirus) and purified platelet GPIIb/IIIa demonstrated that the patient's IgG bound specifically, through the F(ab')2 portion, to a common epitope of HIV-GP160/120 and platelet GPIIb/IIIa. This common epitope was present on a recombinant GP160 expressed in baculovirus but absent from another recombinant GP160 expressed in vaccinia virus, suggesting that the cross-reactivity is dependent on the glycosylation or conformational structure of the GP. We conclude that molecular mimicry between HIV-GP160/120 and platelet GPIIb/IIIa may explain at least some cases of ITP in AIDS-free HIV-infected patients. PMID- 1611084 TI - Synergism of interleukin-2 and cyclosporine A in induction of a graft-versus tumor effect without graft-versus-host disease after syngeneic bone marrow transplantation. AB - Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD. PMID- 1611085 TI - Elevation of interleukin-6 in response to a chronic inflammatory stimulus in mice: inhibition by indomethacin. AB - Intraperitoneal (i.p.) injection of a mineral oil such as pristane induces a chronic inflammatory response in mice. This is characterized by a large influx of macrophages and other inflammatory cells into the peritoneal cavity for months after injection of the oil. By using the B9 cell bioassay, it was found that injection of pristane caused a marked and prolonged elevation of interleukin-6 (IL-6) levels in the peritoneal cavities of the mice. IL-6 was undetectable (less than 15 U/mL) in the peritoneal fluids of unprimed mice and during the first week after injecting pristane. From 4 to 20 weeks, the concentration of IL-6 increased to an apparent plateau with concentrations ranging from 200 to 2,000 U/mL. Increasing the dose of pristane did not substantially increase the peritoneal levels of IL-6 established at 20 weeks after pristane treatment. At later times (by day 250), the level decreased to 263 +/- 217 U/mL. However, mice that developed plasma cell tumors around day 300 showed high levels of IL-6 in the ascites fluid (650 to 2,400 U/mL). Serum levels of IL-6 were also elevated in pristane-primed mice but were substantially lower than those found in the peritoneal cavity. Chronic administration of the nonsteroidal anti-inflammatory drug indomethacin decreased the levels of IL-6 by 75% to 80%. Experiments performed in vitro showed that pristane-elicited macrophages secreted low levels of IL-6 constitutively and high levels of IL-6 in the presence of lipopolysaccharide. Both IL-6 and prostaglandin E2 production were inhibited by addition of indomethacin to macrophage cultures in vitro. Treatment of mice with pristane may provide a model system for studying the inflammatory pathways that control IL-6 levels in vivo. The relevance of these results to elucidation of the role of IL-6 in plasma cell tumorigenesis is discussed. PMID- 1611086 TI - Merocyanine 540-sensitized photoinactivation of human erythrocytes parasitized by Plasmodium falciparum. AB - The purpose of this study was to evaluate the photosensitizing dye merocyanine 540 (MC540) as a means for extracorporeal purging of Plasmodium falciparum infected erythrocytes from human blood. Parasitized red blood cells bound more dye than nonparasitized cells, and exposure to MC540 and light under conditions that are relatively well tolerated by normal erythrocytes and normal pluripotent hematopoietic stem cells reduced the concentration of parasitized cells by as much as 1,000-fold. Cells parasitized by the chloroquine-sensitive HB3 clone and the chloroquine-resistant Dd2 clone of P falciparum were equally susceptible to MC540-sensitized photolysis. These data suggest the potential usefulness of MC540 in the purging of P falciparum-infected blood. PMID- 1611087 TI - Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization. AB - Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells. PMID- 1611089 TI - Improved isolation of normal human reticulocytes via exploitation of chloride dependent potassium transport. AB - Studies on normal human reticulocytes have been limited by a lack of methods for effective reticulocyte enrichment. This study shows a convenient new approach for selective enrichment of reticulocytes from normal blood samples. We have developed a modified arabinogalactan density gradient that contains high potassium levels, approximating the internal cation composition of red blood cells (RBC). The low-density populations from this gradient are enriched in reticulocytes, and the highly selected lowest density fraction shows a much higher reticulocyte enrichment than that obtained with high sodium chloride arabinogalactan density gradients, or other previously reported density gradient methods. We found that this improved isolation is caused by suppression of potassium loss and reticulocyte dehydration via chloride (KCI) cotransport. When the low-density fraction of RBC from a high-potassium gradient was subsequently incubated in high sodium chloride medium and reseparated on a sodium chloride density gradient, the reticulocytes dehydrated and were recovered in high-density fractions. The highest-density fractions from this secondary gradient yield 95% to 99% reticulocytes. We anticipate that this method will benefit investigators who require reticulocyte enriched populations for a wide variety of applications. PMID- 1611088 TI - Characterization of multiple quinine-dependent antibodies in a patient with episodic hemolytic uremic syndrome and immune agranulocytosis. AB - A 23-year-old woman experienced six distinct episodes of severe combined neutropenia and thrombocytopenia. At least one of the episodes was accompanied by hemodialysis-requiring acute renal failure and fragmentation hemolysis (hemolytic uremic syndrome [HUS]). In retrospect, all episodes were probably associated with the ingestion of quinine. Quinine-dependent antibodies to platelets, neutrophils, T lymphocytes, and red blood cells (RBCs) were detected in the patient's serum. By a monoclonal antibody antigen capture assay, the patient's serum contained IgG antibodies, which in the presence, but not absence, of quinine reacted with platelet glycoprotein (GP) complexes Ib/IX and IIb/IIIa, but not Ia/IIa. By immunoprecipitation assay, the serum, after addition of quinine, reacted strongly with an 85-Kd neutrophil membrane protein and weakly with 130- and 60-Kd moieties. Serum adsorbed with RBCs in the presence of quinine continued to react with platelets and neutrophils, and serum that was absorbed with platelets continued to react with neutrophils and RBCs, indicating that the antigenic targets were different on platelets, neutrophils, and RBCs. Since platelets and endothelial cells share some antigens, we tested patient serum for antibodies to human umbilical vein endothelial cells (HUVEC); no quinine-dependent antibodies to HUVEC were detected. However, her quinine-dependent antibodies not only bound to platelets and neutrophils, but also activated neutrophils. Thus, the patient's serum with quinine aggregated neutrophils, but neither agent alone caused activation. Moreover, the patient's serum with quinine (but not without) augmented the adherence of neutrophils to HUVEC. Treatment of the patient's serum with staphylococcal protein A removed the quinine neutrophil aggregation cofactor, suggesting it was due to IgG. In both neutrophil aggregation and adherence assays, decomplementation of the patient's serum markedly blunted its effect. Furthermore, the patient's serum failed to aggregate formalin-inactivated neutrophils, suggesting neutrophil activation, probably by activated complement, was necessary for aggregation and adhesivity to endothelium. We conclude that our patient's neutropenia, thrombocytopenia, lymphopenia, and anemia were due to quinine-dependent antibodies, and that these antibodies recognized epitopes that were different in the three target cell populations. We further suggest that HUS was likely secondary to the activation and adhesion of neutrophils to endothelium. PMID- 1611090 TI - Measurement of basal levels of factor VIIa in hemophilia A and B patients. AB - Previous results, presented in abstract form, indicate that replacement of thromboplastin with a mixture of phospholipid and truncated soluble tissue factor apoprotein results in a coagulation assay that can directly measure plasma factor VIIa levels without interference from zymogen factor VII (Atherosclerosis Thromb 11:1544a, 1991 [abstr]). We have exploited the specificity and sensitivity of such a factor VIIa specific coagulation assay to directly assess the in vivo relationship of factor VIII and factor IX on the production of factor VIIa levels under nonthrombotic and nonstimulatory conditions. Normal individuals (n = 20) were found to possess an average circulating factor VIIa level corresponding to 4.34 +/- 1.57 ng/mL, or approximately 1% of their total factor VII antigen. Severe factor VIII deficient patients (n = 13) possessed a slightly lower but statistically significant (P less than .01) decrease in their basal factor VIIa levels (2.69 +/- 1.52 ng/mL), corresponding to approximately 60% of that observed in normal individuals. On the other hand, severe factor IX deficient patients (n = 7) were found to possess even lower levels of factor VIIa corresponding to 0.33 +/- 0.15 ng/mL, or less than 10% of that observed in normal individuals. Measurement of total factor VII antigen levels shows that the variation in basal factor VIIa levels stems from differences in the degree of factor VII activation as opposed to differences in factor VII antigen levels. Our present data are consistent with the hypothesis that factor IXa is the principal in vivo activator of factor VII under basal conditions. PMID- 1611091 TI - New glucose-6-phosphate dehydrogenase mutations from various ethnic groups. AB - Seven new mutations that produce glucose 6 phosphate dehydrogenase (G6PD) deficiency are described. Three are in variants that were biochemically characterized and described previously, while four were found in samples that had not been characterized biochemically. Several of the mutations affect the amino acids that are mutated in other G6PD variants. As had been noted previously, variants that are associated with nonspherocytic anemia are located either near the glucose 6 phosphate or the NADP binding sites. Variants more distant from these sites are not associated with chronic hemolysis. PMID- 1611092 TI - Molecular basis for the human erythrocyte glycophorin specifying the Miltenberger class I (MiI) phenotype. AB - Human glycophorin Mil (HGpMil) is a structural variant of the MNSs blood group system that specifies the Miltenberger class I phenotype. We report here the molecular basis of the HGpMil gene identified in a white family in which the first homozygote was encountered. Immunoblotting analysis showed the expression of HGpMil and HGpB but the absence of HGpA on the homozygous Mil erythrocytes. Southern blot analysis detected no gross alterations in gene structure or band intensity. Genomic sequences encompassing exons II and III of the HGpMil gene were amplified by single-copy polymerase chain reaction. Restriction digestion and direct DNA sequence analysis showed that HGpMil gene is derived from an alpha N allele of HGpA and differs from the latter in the third exon by a single nucleotide change. In HGpMil, the presence of a deoxythymidine at the second position of codon 28 (ATG) not only resulted in a methionine substitution but also altered the consensus sequence for N-glycosylation from Asn-Asp-Thr to Asn Asp-Met. These data are consistent with the occurrence of Mil on the red blood cell membrane as a variant deficient in the asparagine-linked carbohydrate unit. Significantly, this particular point mutation lies in between the two half-sites of a direct repeat that has been implicated to facilitate the recombination events leading to several other glycophorin genes of the Miltenberger series. Based on this relatedness, we propose an untemplated nucleotide replacement resulting from a gene conversion event as the molecular basis for the origin of HGpMil gene. PMID- 1611093 TI - Circulating stem cells in mice treated with cyclophosphamide. AB - Chemotherapy has been used clinically to mobilize hematopoietic progenitor cells into the peripheral blood so that they can be harvested for autologous transplantation. In humans, this is demonstrated by the presence of circulating granulocyte-macrophage colony-forming cells (CFU-GM) and CD34-positive cells, but it has not been possible to confirm the presence of marrow-repopulating stem cells. In this study, we treated mice with 200 mg/kg cyclophosphamide (CY) and measured the numbers of white blood cells, day 12 CFU-S (CFU-S12), and CFU-GM in the peripheral blood. There was a peak in the numbers of CFU-S12 and CFU-GM 8 days after treatment with cyclophosphamide. Peripheral blood cells taken at this time rescued lethally irradiated mice and engraftment of donor cells was confirmed after 140 days in sex mismatched recipients using a Y chromosome specific probe. In vitro culture of the blood cells harvested after cyclophosphamide showed that they proliferated in suspension cultures for at least a year in the presence of interleukin-3. The cultured cells rapidly lost their abilities to rescue irradiated mice and to form colonies in vitro, but they did not become leukemic. Also, CY-treated mice were irradiated with a leukemogenic dose of x-rays to coincide with peak circulating cell numbers but these animals did not develop an excess of leukemias over mice given irradiation alone. PMID- 1611094 TI - Unrelated donor bone marrow transplantation for correction of lethal congenital immunodeficiencies. AB - Unrelated donor marrow transplantation was undertaken in eight infants with severe combined immunodeficiency (SCID) and two children each with Wiskott Aldrich syndrome (WAS) and Chediak-Higashi syndrome (CHS) who did not have histocompatible siblings. Donors for three patients were phenotypically matched at all HLA-A, B, Dr, and Dw loci, whereas nine donors were mismatched from the recipients at one of the HLA-A or B loci but phenotypically identical at evaluable D loci. All but one patient received conditioning chemotherapy and/or radiotherapy before infusion of donor marrow, which was not T-cell depleted. Prophylaxis for graft-versus-host disease (GVHD) consisted of methotrexate and prednisone combined with either cyclosporine A (six patients), antithymocyte globulin (five patients), or anti-CD5 ricin A chain immunotoxin (one patient). All patients engrafted with donor cells, and only 4 of 12 experienced any GVHD (1 of 8 SCID, 1 of 2 WAS, 2 of 2 CHS). Two children who developed grade II and two who developed grade III GVHD were successfully treated and all are now alive, off immuno-suppressive therapy, with no evidence of chronic GVHD greater than 18 months after transplant. Ten patients are alive with excellent immunoreconstitution greater than or equal to 1 year to greater than or equal to 3 years after transplant; actuarial survival is predicted to be 83% with a median follow-up of 2 years. Two children with SCID succumbed to pre-existing opportunistic infection early posttransplant. We conclude that closely matched unrelated donor bone marrow transplantation can correct congenital immunodeficiencies including variants of SCID, WAS, and CHS, with an acceptably low incidence of transplant-related complications, principally GVHD. PMID- 1611095 TI - Malabsorption of vitamin B12 from the intestine in a child with cblF disease: evidence for lysosomal-mediated absorption. PMID- 1611096 TI - Interactions between recombinant human erythropoietin and serum factor(s) on murine megakaryocyte colony formation. AB - We investigated the interactions between human erythropoietin (hEpo) and serum factor(s) on murine megakaryocyte (MK) colony formation. Serum-free cultures supported the growth of a large number of murine MK colonies in the presence of murine interleukin-3 (mIL-3). The addition of fetal calf serum (FCS) to mIL-3 containing cultures resulted in only a minimal increase in the number of murine MK colonies. In contrast, hEpo alone had no murine MK colony-stimulating activities in serum-free cultures. hEpo required the presence of FCS, murine serum, or human serum in cultures to promote murine MK colony growth and synergized with these sera to stimulate murine MK colony formation. Furthermore, sera from patients with aplastic anemia showed higher synergistic activities with hEpo than sera from hematologically normal persons (normal human serum). When normal human serum was fractionated by gel-filtration chromatography, two peaks with the synergistic activity were observed in the eluent. However, serum did not show any synergistic effects with hEpo on the growth of murine GM colonies or murine colony-forming unit-erythroid-derived colonies. Although human serum synergized with hEpo to stimulate murine MK colony formation, human cytokines such as IL-3, IL-4, IL-6, granulocyte-macrophage colony-stimulating factor (GM CSF) and granulocyte-CSF (G-CSF) failed to induce murine MK colony formation in Epo-containing cultures. In cultures containing human IL-1 alpha + human IL-6 + hEpo as well as in cultures containing hEpo, human IL-3 and human GM-CSF failed to show stimulatory effects on murine MK colony formation. Moreover, the synergistic activity of human serum with hEpo could not be neutralized by antibodies such as antihuman IL-1 alpha, antihuman IL-3, antihuman IL-4, antihuman IL-6, antihuman G-CSF, and antihuman GM-CSF. Our data show that serum contains a growth factor(s) that synergizes with Epo to stimulate the proliferation and differentiation of MK precursors, and strongly suggest that this factor(s) is an unique growth factor(s) that is distinct from IL-1 alpha, IL 3, IL-4, IL-6, G-CSF, and GM-CSF. PMID- 1611097 TI - Characterization, growth, and differentiation of a human myeloid leukemia cell line, TI-1 cell. AB - A cell line (TI-1) has been established from the peripheral blood of a patient with acute myeloid leukemia (M2). A typical TI-1 cell displayed many abnormalities of its chromosomes, but not the Philadelphia (Ph1) chromosome. Light and electron microscopic examination and histochemical analysis indicated that the TI-1 cells were undifferentiated blast cells, but immunologic marker studies suggested that these cells had myeloid characteristics. The proliferation of TI-1 cells was dependent on the concentration of fetal bovine serum (FBS). Their doubling time was 13.8 hours when they were cultured in a medium containing 10% FBS. Phorbol-12 myristate 13-acetate (PMA) induced the TI-1 cells to differentiate into monocyte-like cells, as judged by their morphologic similarity to monocytes, their adhesion to the culture dish, and their increase of both nitroblue tetrazolium (NBT)-reducing ability and nonspecific esterase (NSE) activity. PMA significantly inhibited the proliferation and DNA synthesis of TI-1 cells in a dose-dependent manner. The PMA-induced differentiation was significantly inhibited by the protein kinase C inhibitors (H-7, staurosporine). Hemin induced the TI-1 cells to differentiate into erythroid cells. The number of hemoglobin-producing cells and hemoglobin production was increased by hemin treatment. Hemin also inhibited the proliferation of the TI-1 cells. Thus, the TI 1 cell represents a bipotent, granulo-monocytoid, and erythroid cell line. The TI 1 cell line will be a useful model for monocytoid and erythroid differentiation. PMID- 1611098 TI - Down-regulation of human protein kinase C alpha is associated with terminal neutrophil differentiation. AB - We have established an RNase protection method to quantify the expression of mRNA for the human protein kinase C (PK-C) isoforms alpha, beta 1, beta 2, and gamma. This was used to investigate whether each isoform is differentially expressed during the differentiation of hematopoietic cells. Myeloid and lymphoid cells express PK-C alpha, beta 1, and beta 2 mRNAs in various proportions. PK-C gamma mRNA was detected in human brain, but not in hematopoietic cells. PK-C alpha mRNA decreases as HL-60 cells mature to a neutrophil phenotype in response to retinoic acid, but its abundance does not change during monocytic differentiation in response to vitamin D3. PK-C alpha mRNA and protein were undetectable in peripheral blood neutrophils, but are present in monocytes. The mRNAs for PK-C beta 1 and beta 2 isoforms increase during HL-60 differentiation and are expressed in both neutrophils and monocytes. Therefore, the PK-C alpha isoform is specifically down-regulated during human neutrophil terminal differentiation. These data suggest that mature neutrophil functions do not require the PK-C alpha isoform. PMID- 1611099 TI - Separation of hematopoietic stem cells into two populations and their characterization. AB - Two populations of hematopoietic stem cells (HSC) in mouse bone marrow (BM) are defined on the basis of the presence or absence of interleukin-3 (IL-3) receptor associated antigen (IL-3RAA). HSC were purified by depletion of mature lymphoid lineage cells followed by collection of the low-density fraction and sorting of wheat germ agglutinin-binding (WGA+) cells using a fluorescein-activated cell sorter. WGA+ cells were further separated into two populations (IL-3RAA+/WGA+ and IL-3RAA-/WGA+) by a monoclonal antibody (MoAb) against IL-3RAA. IL-3RAA+/WGA+ cells formed CFU-S on day 8; this population consisted mainly of cells in the cycling phase. IL-3RAA-/WGA+ cells form CFU-S on day 12; this population consisted mainly of dormant cells (cells in the G0 phase). When two populations obtained from C3H/HeN mice were injected into lethally irradiated (C57BL/6 x C3H/HeN)F1 mice, donor-derived cells in the peripheral blood (PB) appeared significantly earlier in mice injected with IL-3RAA+/WGA+ cells than in those injected with IL-3RAA-/WGA+ cells, whereas the reconstruction efficiency of IL 3RAA-/WGA+ cells had overtaken that of IL-3RAA+/WGA+ cells 6 weeks after injection. Long-term observation showed no significant difference between these two populations, however. The radioprotective ability (RPA) (30-day survival) of these two populations was therefore compared. The RPA of IL-3RAA-/WGA+ cells was significantly higher than that of IL-3RAA+/WGA+ cells. These findings therefore suggest that the former population is more primitive. PMID- 1611100 TI - The topic of quality has always been fraught with issues of changing terminology. PMID- 1611101 TI - Basic statistical concepts in quality improvement. PMID- 1611102 TI - Measuring patients' perceptions of care quality. PMID- 1611103 TI - Developing and implementing a tool to measure severity of medication errors. PMID- 1611104 TI - Quality of care in weaning from mechanical ventilation. PMID- 1611105 TI - Increasing organ and tissue procurement through quality improvement. PMID- 1611106 TI - Managed care: the missing link in quality improvement. PMID- 1611107 TI - A conceptual framework for evaluation of nursing service quality. PMID- 1611108 TI - Integrating infection control into a nursing quality program. PMID- 1611109 TI - Is quality assessment a professional-only activity? PMID- 1611110 TI - Measuring patient satisfaction as an outcome of nursing care. PMID- 1611112 TI - A pilot study comparing different dose levels and administration schedules of interferon-alpha 2b combined with epirubicin for prevention of recurrence in bladder cancer. AB - A pilot study in 62 patients has been carried out to evaluate the combination of epirubicin and interferon (IFN)-alpha 2b using different doses and schedules of intravesical administration in the prevention of recurrence of bladder cancer. Preliminary results show greater prophylactic efficacy not only when higher doses of epirubicin and IFN-alpha 2b are used but also when a larger interval between instillation of the compounds was used. PMID- 1611111 TI - High-dose versus low-dose intravesical interferon-alpha 2b in the treatment of carcinoma in situ: a randomized, controlled study. AB - Eighty-seven patients with carcinoma in situ of the bladder were randomized to receive either 10 MU (low dose, 38 patients) or 100 MU (high dose, 47 patients) of recombinant interferon-alpha 2b intravesically once weekly for 12 weeks and then monthly for up to 1 year. The 100 MU dose produced a significantly greater incidence of complete responses than the 10 MU dose (43 and 5%, respectively), p less than 0.0001. Adverse effects of treatment were infrequent except for mild-to moderate flu-like symptoms, which occurred in 8% and 17% of patients from the low and high-dose groups, respectively. PMID- 1611113 TI - Chemoimmunotherapy for prophylaxis of recurrence in superficial bladder cancer: interferon-alpha 2b versus interferon-alpha 2b with epirubicin. AB - Eighty-five patients who had undergone transurethral resection (TUR) of superficial bladder cancer were randomized to one of two treatments. Patients in Group 1 received a 10-month course of intravesical therapy with interferon (IFN) alpha 2b (50 MU dose), commencing 21 days after TUR once a week for 8 weeks, then once every 15 days for 4 months and then finally once a month for 4 months. Patients in Group 2 received epirubicin (80 mg) intravesically 0, 24 and 48 h after TUR, and then 21 days after TUR received IFN-alpha 2b as for Group 1. The results confirmed the efficacy of immunoprophylaxis with IFN-alpha 2b, and early treatment with epirubicin tended to further reduce the percentage of relapses and extended the disease-free interval. PMID- 1611114 TI - Prospective, randomized trial to evaluate high-versus low-dose interferon-alpha 2b versus conventional chemotherapy in prevention of the recurrence of superficial transitional cell carcinoma of the urinary bladder. AB - Forty-four patients with superficial bladder cancer were randomized to receive 10 MU (14 patients) or 100 MU (14 patients) of interferon (IFN)-alpha 2b or 1.3 g ethoglucid (16 patients) instilled into the bladder once weekly for 10 weeks and then monthly for 1 year. Efficacy (evaluated in 34 patients who completed the course of treatment), based on recurrence rate and time to first recurrence, was similar in the three groups. No systemic toxicity of treatment was seen. Severe chemocystitis occurred in some patients who received ethoglucid (three had to discontinue treatment), while no local toxicity was seen with IFN-alpha 2b treatment. PMID- 1611115 TI - Interferon-alpha 2b instillation prophylaxis in superficial bladder cancer--a prospective, controlled three-armed trial. Project Group Bochum--Interferon and Superficial Bladder Cancer. AB - Sixty-seven patients with recurrent pTa G1-G3 to pT1 G1-G3 tumors were randomized into three groups receiving either Intron A at 10 MU/instillation, Intron A at 10 MU and mitomycin C (MMC) at 20 mg/instillation or MMC at 20 mg/instillation. After a mean follow up of 6.2 months no tumor recurrence has been seen in the group receiving combined therapy, whilst four out of 22 in the interferon group and five out of 23 in the MMC group suffered a recurrence. Side effects were slight. These preliminary results suggest that a combination of the two drugs is more effective than either drug alone. PMID- 1611116 TI - Diagnosis and treatment of bladder cancer. AB - The primary key to diagnosis of bladder cancer is cystoscopic examination of the bladder, followed by biopsy of suspicious lesions. Bimanual examination under anesthesia is also important for staging, and urinary cytology and intravenous urography provide valuable additional information. Surgical resection in the form of excisional transurethral biopsy is diagnostic, therapeutic and essential for accurate staging, and assessment of tumor grade is vital for determining prognosis and management strategies. Intravesical chemotherapy with Thiotepa, doxorubicin, mitomycin C or ethoglucid has been shown to reduce the incidence of short-term tumor recurrence by 17% but not long-term recurrence or rate of disease progression. Immunotherapy, as exemplified by Bacillus Calmette-Guerin (BCG), has achieved better results: long-term reduction in tumor recurrence, reduction in disease progression and prolongation of patient survival. Newer immunotherapies using interferon-alpha appear to produce response rates comparable to BCG but without the considerable toxicity of BCG. Further research with combination therapies and other immunotherapeutic agents should lead to improved treatment options in the future. PMID- 1611117 TI - Immunomodulatory effect of interferon-alpha 2b on natural killer cells and T lymphocytes from patients with transitional cell carcinoma of the bladder. AB - Incubation of peripheral blood mononuclear cells (PBMNC) from patients with transitional cell carcinoma of the bladder, with interferon (IFN-alpha 2b) causes dose-dependent enhancement of natural killer (NK) and cytotoxic activity. Increased lytic activity was also observed against both NK-sensitive and NK resistant target cells and T lymphocytes from such patients showed altered activity upon incubation with IFN-alpha 2b. Furthermore, intracavitary instillation of IFN-alpha 2b is associated with infiltration of the bladder wall by NK cells and T lymphocytes. Future work will be aimed at investigating the possible prognostic value of these results as related to the therapeutic effect of intracavitary instillation of IFN-alpha 2b. PMID- 1611118 TI - Analysis of the effect of intravesical treatment with interferon-alpha 2b on the clinical evolution and on the in vivo function of T lymphocytes and natural killer cells in patients with superficial bladder tumors. AB - Following complete transurethral resection, patients with superficial transitional cell carcinoma (TCC) were treated with intravesical interferon-alpha 2b. Ex vivo analysis of peripheral blood mononuclear cells (PBMNC) both during and after the treatment period showed an enhancement of natural killer (NK) activity which fell to basal levels upon cessation of therapy. Simultaneous analysis of T-cell activity revealed a similar pattern of variation in the response to the polyclonal mitogen phytohemagglutinin. Both findings point to an alteration in systemic immunoreactivity as a result of intravesical treatment. Further work will be aimed at determining whether this is relevant to the therapeutic value of such treatment and whether prolonged treatment will maintain these effects. PMID- 1611119 TI - [Potential for spread of HIV in Japan]. AB - Beginning 3 years ago, rapid spread of HIV was observed in Thailand with consequent serious problems in the public. HIV initially spread among i.v. drug abusers and then invaded prostitutes. Sero-surveillance estimates that there are 300,000 HIV positives in all of Thailand. Thai authorities warn that 4 million persons may be infected by the year 2000. In Japan, the cumulative number of HIV positives is reported as 453 excluding hemophiliac cases. However, the reported figures are assumed to be only a part of the actual figure. WHO estimates there may be 20,000 HIV positives in Japan. From the epidemiological surveillance, incidence of HIV positives even in the risk groups is extremely low in Japan. HIV positives in blood donors is merely 0.31 per 100,000. The question is whether AIDS will continue to be a less serious problem in Japan? Examination of blood or a voluntary basis may not tell the real situation of HIV positives in Japan. There is a real concern regarding HIV positives in female foreign visitors who made up 86 per cent of all female positives in Japan. These females are suspected to be professionals engaged in sex business in Japan. A hypothetical simulation indicates they may possibly infect 60,000 people per year. On the other hand, contact between Japanese travellers visiting Thailand and Thai prostitutes is also possible. Using the figure of 230,000 males visiting Thailand in 1990, hypothetical simulation revealed that 690 may become infected per year which is 1/50 of those calculated to be infected inside Japan.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611120 TI - [Global environmental changes and health from a viewpoint of human ecology]. PMID- 1611121 TI - [Efficacy of individual smoking cessation instructions for general smokers among clients of a health center]. AB - Smoking cessation instruction for individuals using a standardized smoking cessation manual and a handout developed by the authors was studied in a controlled trial among employees who visited a health center for Industrial Safety and Health Law mandated annual health examinations. Smokers in the study group were given 5-10 minutes smoking cessation instruction mainly by public health nurses and nutritionists following the above-mentioned manual and using the handouts. Subjects in both groups were interviewed by telephone to assess changes in smoking habits one month after the first contact. Smoking clients who came on Friday (132) and on Monday (93) were assigned to study and control groups, respectively. One hundred and nineteen members (90.2%) of the study group and 88 (94.6%) of the control group were successfully followed until one month after the initial contact. Seven subjects in the study group were not smoking one month after the instruction, while no one gave up smoking in the control group (p less than 0.05). It was confirmed by telephone survey that 6 of the 7 subjects who were not smoking at one month were still maintaining abstinence from smoking one year after the instruction. Smokers who did not stop smoking reported a reduction in their smoking dose in the study group. Lighter smokers reacted more readily to instruction than did heavier smokers and the knowledge level of subjects was positively associated with the success rate. PMID- 1611122 TI - [Effects of exercise and calcium-intake on bone hardness and bone constituents in aged mice]. AB - Effects of exercise and differing calcium intakes on bone hardness and bone constituents were examined using mice (40 weeks old) in successive stages of senescence to contribute to our understanding of preventive measures against osteoporosis. In the present study, the mice were divided into four groups, combinations of stock diet (Ca: 1.25 g/100 g) or low Ca diet (Ca: 0.15 g/100 g), with or without physical exercise (forced exercise, 40 min/day at a velocity of 12 m/min) and maintained in their respective conditions for 16 weeks. Autopsies were performed or representative mice every four weeks (44, 48, 52, 56 weeks old). The obtained results are summarized as follows: 1) In female mice highest values for femoral bone weight were observed after 48 weeks in the mice exposed to forced exercise and on a stock diet and had a significant difference from the other groups. No difference was observed in male mice. 2) Bone hardness had a tendency to be reduced with age in all groups. The velocity of diminution was small in the mice kept on stock diet as compared to those on a low Ca diet. The highest bone hardness was observed in the mice kept in forced exercise and stock diet group at every stage. 3) Bone constituents, Ca, P and hydroxyproline, showed no differences in concentration per weight of bone. But higher total content in the femur was obtained in the mice kept on a stock diet. 4) No differences in concentration of serum calcitonin and parathormone were seen in every group of male mice.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611124 TI - [Comparative evaluation of membrane filter methods for enumeration of enterococci in water]. AB - Many laboratory methods for the assay of viable counts of enterococci in water have been reported, but the evaluation or verification of the methods have yet to be reported. The three most commonly used membrane filter methods were selected and compared in terms of the verification of enterococci counts in environmental water. The verified percentages, i.e. identified enterococci count versus apparent enterococci count, assayed by each method, were as follows: KF.MF (membrane filter cultured on KF agar) method 64.5%; mENT.MF (membrane filter cultured on mENT agar) method 80.7%; and mE.MF (membrane filter cultured on mE agar) method 63.4%. The AC.MF (membrane filter cultured on AC agar) method which we reported previously (Koujima I, et al. Jap J Bact, 1989; 44: 813-816) consistently gives 100% verification and therefore is the most consistent method and superior in accuracy to the other three methods. PMID- 1611123 TI - [A comparative study of the characteristics and social backgrounds of frail and elderly persons at home, long-stay elderly hospital patients, and residents of welfare homes for the frail elderly]. AB - Three studies were carried out in Mino City, Osaka Prefecture, on 188 frail and elderly persons living at home (the home group), 61 elderly patients who had been hospitalized more than six months (the inpatient group), and 72 residents of welfare homes for the frail elderly (the resident group). The characteristics and social backgrounds of the three groups were compared. About 30% of each group had suffered a stroke. As for ADL score, moderate disability was dominant in the home group, severe disability in the inpatient group, and slight disability in the resident group. The proportions of those who had been living alone and those who had no spouse were significantly higher in the inpatient group and in the resident group than in the home group. Significantly fewer subjects in the resident group had been living with their offspring than in the home group or in the inpatient group. The percentage of those who did not have their own home was the highest for the resident group. Multivariate analyses using Hayashi's quantification method II were conducted for a comparison between cases belonging to the home group and the inpatient group, and between the home group and the resident group. The analysis of the home group and the inpatient group revealed a relationship of the inpatient group to severe disability in ADL, and living alone. Differences between these two groups were related to such variables as ADL, sex, living or not living alone, living or not living with offspring, and having or not having a spouse.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611125 TI - [A study of the relation of dietary intake during pregnancy to birth weight]. PMID- 1611126 TI - Evidence of multiple circadian oscillators in bean plants. AB - Circadian rhythms in stomatal opening and photosynthesis had shorter free-running periods than circadian rhythms in leaflet movement in bean plants (Phaseolus vulgaris L.) transferred from 12-hr photoperiods to constant conditions. The rhythm in leaflet movement had a period close to 27 hr, whereas the rhythm in stomatal opening, measured as conductance to water vapor, had a period close to 24 hr. Photosynthesis, measured as net assimilation of CO2, also oscillated with a period close to 24 hr. The periods of these rhythms did not vary with increasing temperature, demonstrating temperature compensation of the controlling oscillators. The difference in free-running periods displayed by these rhythms is evidence that multiple oscillators with different intrinsic frequencies operate in bean plants. PMID- 1611127 TI - The effects of temperature on the circadian rhythms of flashing and glow in Gonyaulax polyedra: are the two rhythms controlled by two oscillators? AB - Circadian rhythms of flashing and glow were recorded simultaneously in Gonyaulax polyedra by determining maximum and minimum light emission at each measured interval of 28 sec. In constant light, the two rhythms in some cases showed different period lengths (tau), the glow rhythm being up to 1 hr shorter than the flashing rhythm. Lower temperatures shortened the tau of the glow rhythm more than that of the flashing rhythm. The amplitude of the flashing rhythm decreased when the temperature was increased from 15 degrees C to 25 degrees C, whereas that of the glow rhythm was increased. These results may indicate that the two rhythms are controlled by two separate oscillators. PMID- 1611128 TI - NMDA as well as non-NMDA receptor antagonists can prevent the phase-shifting effects of light on the circadian system of the golden hamster. AB - The present experiments were designed to evaluate whether the intraventricular administration of excitatory amino acid (EAA) receptor antagonists would prevent light-induced phase shifts of the circadian rhythm of wheel-running activity in the hamster. Administration of the non-N-methyl-D-aspartate (non-NMDA) antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) blocked light-induced phase advances and delays. Similarly, administration of the competitive NMDA receptor antagonist, 3(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), prevented light induced phase advances and delays. Neither drug by itself caused any consistent effect on the phase of the rhythm. These data provide further evidence that EAA receptors mediate the effects of light on the circadian system, and suggest that both NMDA and non-NMDA receptor types may be involved. PMID- 1611129 TI - Changes in the phase response curve of the circadian clock to a phase-shifting stimulus. AB - Experiments were conducted in hamsters to determine whether the phase response curve (PRC) to injections of the short-acting benzodiazepine triazolam is a fixed or a labile property of the circadian clock. The results indicated that (1) both the shape and the amplitude of the PRC to triazolam generated on the first day of transfer from a light-dark cycle (LD 14:10) to constant darkness (DD) (i.e., PRCLD) were different from those of the PRC generated after many days in DD (PRCDD); and (2) the phase-shifting effects of triazolam on the activity rhythms of hamsters transferred from LD 14:10 or 12:12 to DD changed dramatically within the first 8-9 days spent in DD. In an attempt to accelerate the resynchronization of the circadian clock of hamsters subjected to an 8-hr advance in the LD cycle, triazolam was given to the animals at a time selected on the basis of the characteristics of PRCLD. The activity rhythms of five of eight triazolam-treated animals were resynchronized to the new LD cycle within 2-4 days after the shift, whereas those of most of the control animals were resynchronized 21-29 days after the shift. These findings suggest that attempts to use pharmacological or nonpharmacological tools to phase-shift circadian clocks under entrained conditions should take into account information derived from PRCs generated at the time of transition from entrained to free-running conditions. PMID- 1611130 TI - Anticipatory activity rhythms under daily schedules of water access in the rat. AB - Rats anticipate a fixed daily feeding time by entrainment of a component of their multioscillatory circadian system. The range of stimuli capable of entraining this component is little studied. Previous studies suggest that restricted water access is not an effective entrainment stimulus, as measured by general locomotion. The present study re-examined the issue, using two other measures of activity: wheel running and activity at a food-water delivery bin. Rats restricted to 1 hr of water each day in the middle of the light and to food in the 12-hr dark period showed no anticipation of this event in the wheel-running measure, but some rats did show anticipation in the delivery bin activity measure. Rats (bin activity measure only) restricted to 1 hr of water and 1 hr of food separated by intervals of 7, 10, or 12 hr, in either the light or the dark, showed consistent anticipation of food access time but little or no anticipation of water access time. Water access time also did not sustain food anticipatory rhythms in animals whose food-water schedules were reversed. However, deprivation of water or of both food and water for 72 or 90 hr was usually associated with specific increases in bin activity at both the usual feeding and drinking times. Water access, like food, appears to provide cues capable of entraining an anticipatory circadian mechanism. Differences in the type and amount of anticipatory activity preceding these events may reflect differences in the strengths of the two entrainment cues and/or in the activity levels or specific behavioral strategies promoted by hunger and thirst. PMID- 1611131 TI - Evidence for genetic variation in the occurrence of the photoresponse of the Djungarian hamster, Phodopus sungorus. AB - The Djungarian hamster generally responds to a short-day photoperiod with a complex syndrome of physiological and behavioral changes; however, not all hamsters are photoresponsive. The phenotypic difference is, in part, genetically determined. Parent-offspring regression on a number of continuous and discontinuous measures indicated significant heritability for photoresponsiveness. Four generations of replicated bidirectional selection on a photoresponse index (PI) resulted in significant shifts in the percentage of responsive hamsters, although the average PI of responsive individuals was not significantly changed. Eight estimates of heritability ranged from 0.20 to 0.52. We hypothesize that the circadian system is responsible for the occurrence of the photoresponse, but that the extent of photoresponse is controlled by a separate functional system. PMID- 1611132 TI - The topology of phase response curves induced by single and paired stimuli in spontaneously oscillating chick heart cell aggregates. AB - The topological properties of the phase resetting of biological oscillators by an isolated stimulus delivered at various phases of the cycle depend on whether the stimulus is "weak" or "strong." When multiple stimuli are delivered to the oscillator, the response to stimulation also depends on the time between the stimuli, and the rate at which the oscillator returns to an underlying limit cycle attractor. If the time between two consecutive "weak" stimuli is sufficiently short, the effects produced by the pair of stimuli may be characteristic of a single "strong" stimulus. These results are demonstrated in a model experimental system, spontaneously beating aggregates of cells derived from embryonic chick heart, and are illustrated by consideration of a simple theoretical model of nonlinear oscillators, the Poincare oscillator. PMID- 1611133 TI - Personality traits as predictors of good diabetic control. AB - To identify personality characteristics that might contribute to overall good control of type I diabetes mellitus, we used a biological correlate of control, glycosylated hemoglobin A1c values, as a means of selecting patients. Patients with evidence of good control (HbA1c less than 7.5%) were compared with patients with evidence of poor control (HbA1c greater than 10.4%). All patients were administered the Personality Research Form E. Need for achievement and a socially desirable response style were associated with good glycemic control. This finding is placed in the context of the complexity of health care behaviors required for adequate self-management. PMID- 1611134 TI - No correlation between glycemic control and an increase in erythrocyte aldose reductase activity in type I and type II diabetic patients. AB - Aldose reductase, the first enzyme of the polyol pathway, has been related to the pathogenesis of diabetic complications. The regulation of the enzyme in diabetes patients, however, has not yet been clarified. We recently reported that the activity of aldose reductase was increased in erythrocytes of insulin-dependent diabetes mellitus patients but short-term hyperglycemia did not affect the enzyme activity. It is still unclear, however, whether or not the increase in the enzyme activity is caused by long-term hyperglycemia and thus would be seen equally in both type I (insulin-dependent diabetes mellitus) and type 2 (non-insulin dependent diabetes mellitus) individuals. To further clarify these issues we measured erythrocyte aldose reductase activity in 46 type I patients and 30 type II patients who had variable glucose control and in 16 nondiabetic subjects. We compared the enzyme activity with plasma glucose levels and hemoglobin A1c levels. The results show that erythrocyte aldose reductase activity is increased in both type I and type II patients as compared with nondiabetic subjects (7.1 +/ 0.3 U/L and 6.8 +/- 0.4 U/L erythrocytes versus 5.6 +/- 0.2 U/L erythrocytes, p less than 0.001 and p less than 0.01, respectively), but there were no significant differences between the two groups of diabetic patients. The enzyme activity varied by approximately four times among the diabetic individuals but there was no correlation between the enzyme activity and plasma glucose or hemoglobin A1c levels. We conclude that the increased activity of erythrocyte aldose reductase seen in diabetes is not related to hyperglycemia. PMID- 1611135 TI - Relationship of lipid peroxides to diabetic complications. Comparison with conventional laboratory tests. AB - One hundred and seventy-three Arab patients with non-insulin-dependent diabetes mellitus (NIDDM) and 51 controls were examined. The routine laboratory tests of fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), fructosamine (FRA), and triglycerides (TG) were compared with lipid hydroperoxides (LHP) as detected by the thiobarbituric acid (TBA) method, which measures total TBA reacting substances (TBARS). All routine laboratory measures were elevated in the patient population. In the case of LHP, values in NIDDM were 491 +/- 183 mumol/L for men and 507 +/- 183 mumol/L for women, as compared with pooled normal values of 275 +/- 85 mumol/L. Seven patients with NIDDM undergoing hemodialysis were also elevated above normal (441 +/- 97 mumol/L). Comparisons between LHP and the other biochemical parameters indicated a positive statistical correlation with triglycerides (p less than 0.001); FBS, HbA1c, and FRA (p greater than 0.01). Patients with NIDDM on dietary control had somewhat lower LHP levels (441 +/- 135 mumol/L) than those receiving insulin (519 +/- 206 mumol/L), or oral hypoglycemic agents (518 +/- 177 mumol/L). Dietary maintenance also resulted in reduced FBS and HbA1c levels. Subdivision of patients according to duration of disease and by nationality showed that Kuwaiti nationals had slightly higher LHP values than did patients of other Arabic origin. Women patients (Kuwaiti and non-Kuwaiti) with NIDDM disease duration of greater than 10 years, had LHP levels above those of males (551 +/- 245 versus 478 +/- 126 mumol/L) and, as a group, showed significant enhancement of retinal complications (85.5% versus 55%). A statistically significant trend (p less than 0.08) could be demonstrated between the prevalence of retinopathy and increasing serum LHP levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611136 TI - Peripheral and autonomic nerve function in 259 diabetic patients with peripheral neuropathy treated with ponalrestat (an aldose reductase inhibitor) or placebo for 18 months. United Kingdom/Scandinavian Ponalrestat Trial. AB - The potential of the aldose reductase inhibitor ponalrestat (600 mg daily) to ameliorate diabetic neuropathy was evaluated in 259 diabetes mellitus patients with peripheral neuropathy (defined by abnormal vibration perception threshold and abnormal peroneal motor conduction velocity) in a double-blind placebo controlled clinical trial running for 18 months. Overall, no beneficial effect of ponalrestat on vibration perception thresholds, nerve conduction velocities, and nerve action potential amplitudes was detected. Because vibration perception thresholds and conduction velocities in median, peroneal, and sural nerves did not deteriorate in the placebo group, the potential of ponalrestat to prevent the expected deterioration in peripheral nerve function that occurs with an increased duration of diabetes was not tested. Patients with an abnormal heart rate reaction to standing (abnormal 30:15 ratio; n = 84) on ponalrestat did not deteriorate in this autonomic nerve function test as shown in those on placebo. In conclusion, ponalrestat did not improve peripheral nerve function in diabetes mellitus patients with signs of peripheral neuropathy, although it did ameliorate a deterioration in autonomic nerve function in diabetic patients with signs of autonomic neuropathy. PMID- 1611137 TI - The effect of the aldose reductase inhibitor, ponalrestat, on the progression of diabetic retinopathy. AB - The objective of this study was to evaluate the effects of ponalrestat, an aldose reductase inhibitor, on the progression of diabetic retinopathy. In this study, 62 patients with diabetes mellitus underwent a double-masked placebo-controlled clinical trial comparing the effect of ponalrestat 600 mg per day with a placebo on the progression of diabetic retinopathy. Both groups were comparable in terms of age, gender distribution, diabetes duration, metabolic control, and presence and severity of diabetic retinopathy. Seven-field stereo fundus photographs were performed at 0 (baseline), 12, and 18 months; 49 patients completed the study (26 in the ponalrestat group and 23 in the placebo group). In both treatment groups, a significant progression of diabetic retinopathy as evaluated by the Early Treatment Diabetic Retinopathy Study classification was observed (Wilcoxon Rank Sum Test, p less than 0.05). No difference was observed in the progression of retinopathy between the two treatment groups (p = 0.96). The number of microaneurysms increased in the two study groups (from 5.6 +/- 1.2 to 10.5 +/- 1.3 in the placebo group and from 10.3 +/- 1.4 to 12.7 +/- 1.4 in the ponalrestat group); however, the increase was statistically significant only in the placebo group (p less than 0.05). When the increase in the number of microaneurysms was evaluated by change of category of microaneurysm count, no significant difference was observed. We conclude that ponalrestat at a dose of 600 mg per day has no clinically significant effect on the progression of diabetic retinopathy. PMID- 1611138 TI - Elevation of resting and exercise blood pressures in subjects with type I diabetes and relation to albuminuria. AB - The etiology of diabetic nephropathy is currently unknown, but blood pressure is believed an important risk factor. A total of 173 subjects with type I diabetes who participated in two or more exercise tests with simultaneous measurements of blood pressure (BP) and heart rate were studied. Subjects with diabetes had significantly elevated resting and exercise diastolic and systolic BPs when compared with controls. This was not related to the presence of albuminuria. During exercise, elevation of diastolic BP was present in 65 (38%) of the 173 test subjects. Elevated exercise diastolic BPs among the subjects with diabetes (excluding controls) was present only for subjects with elevated exercise and overnight albuminuria. It is concluded that factors other than early diabetic nephropathy are likely related to elevated resting and exercise BPs in subjects with diabetes compared with controls. Early renal damage, however, is related to further elevations in resting and exercise diastolic BPs within the group of subjects with diabetes. PMID- 1611140 TI - Paecilomyces varioti pneumonia in a patient with diabetes mellitus. AB - Paecilomyces is a saprophytic soil fungus that is an uncommon human pathogen. We report a diabetic patient who developed an upper lobe pulmonary infection due to Paecilomyces varioti. This pneumonia responded poorly to oral imidazole therapy with ketoconazole. Eventual treatment of the chronic infiltrating process required administration of intravenous amphotericin B. This experience emphasizes the potential pathologic nature of this fungus when immunity is compromised by poorly controlled diabetes. PMID- 1611141 TI - Aldose reductase inhibitors--hope or hype. PMID- 1611139 TI - The role of magnesium in diabetes mellitus. A possible mechanism for the development of diabetic complications. PMID- 1611142 TI - Vascular risk factors in Japanese non-insulin-dependent diabetic patients with microalbuminuria. AB - To determine if non-insulin-dependent diabetes mellitus (NIDDM) patients with microalbuminuria would have augmented vascular risk factors, we studied the relationships between blood pressure, serum lipids, plasma fibrinogen, and uric acid concentrations and plasma lipoprotein (a) level in 25 Japanese NIDDM patients with microalbuminuria [albumin excretion rate (AER) 20-200 micrograms/min] and 25 individually pair-matched NIDDM patients with normal urinary albumin excretion (AER less than 20 micrograms/min), matched for age, sex, body mass index, treatment and HbAlc level. Microalbuminuric patients had significantly higher systolic blood pressure (p less than 0.05) and plasma fibrinogen level (p less than 0.05) and lower high-density lipoprotein (HDL) cholesterol concentration (p less than 0.05) as compared with those in normoalbuminuric patients, respectively, while there were no differences in serum triglycerides and uric acid levels between the two groups. Plasma lipoprotein (a) level, assessed in 15 microalbuminuric and 15 normoalbuminuric patients, was comparable in the two groups. The results suggest that some of the vascular risk factors are already present in microalbuminuric NIDDM patients when compared with normoalbuminuric patients. PMID- 1611143 TI - Cyclosporine in recent onset type I diabetes mellitus. Effects on islet beta cell function. Miami Cyclosporine Diabetes Study Group. AB - To confirm the immunological basis of type I diabetes and to determine if immune intervention alters the course of the disease, we studied the use of cyclosporine in a 1-year randomized, double-masked, placebo-controlled trial in 23 subjects enrolled within 6 weeks of diagnosis. Subjects included 12 males and 11 females, ages 9-38 years (mean, 19.7 +/- 1.8 years). Initial dosage of cyclosporine was 10 mg/kg/day, given as a single daily dose, adjusted on the basis of side effects and trough cyclosporine levels. Glycemic control and insulin dosage were similar in both cyclosporine and placebo groups. The frequency of freedom from insulin usage also was similar in both groups; however, it is not possible to draw conclusions about response rates, because of the very small sample size. Glucose tolerance, as measured by rate of intravenous glucose disposal did not differ between groups. Islet beta cell function was measured by determining C-peptide response to three secretogogues: intravenous glucagon, intravenous glucose, and a mixed formula meal (Sustacal). There were no differences between groups in the C peptide responses either to intravenous glucagon or intravenous glucose. Moreover, acute insulin response to intravenous glucose was not restored in any subject. On the other hand, in comparison to the placebo group, the cyclosporine group did show an increased meal-stimulated C-peptide response after 3, 6, 9, and 12 months. When measured by regression analysis, the slope defining the rate of decline of beta cell function was significantly slower for the cyclosporine group than the placebo group (p less than 0.05). Thus, as measured in response to a physiological stimulus (meal challenge), cyclosporine preserves islet beta cell function when used in recent onset type I diabetes. Side effects were minimal and reversible upon cessation of immune intervention. The preservation of islet beta cell function by immune intervention is consistent with the hypothesis that type I diabetes has an immune mechanism involved in its pathogenesis. PMID- 1611144 TI - von Willebrand factor antigen in plasma and urine in patients with type I (insulin-dependent) diabetes mellitus with and without nephropathy. AB - von Willebrand factor (vWF) antigens were quantitatively and qualitatively analyzed in plasma and urine in 41 patients with type I (insulin-dependent) diabetes. The patients were divided into three groups according to their albumin excretion: group N (n = 24) without any excretion (less than 20 micrograms/min), group M (n = 8) with microalbuminuria (20-200 micrograms/min), and group P (n = 9) with persistent albuminuria (greater than 200 micrograms/min). Healthy subjects served as controls (n = 28). The plasma concentration of vWF was higher (p less than 0.05) in the patients with diabetes mellitus than in the controls. Differences between the groups of patients were not statistically significant. The typical multimeric structure described for vWF in normal plasma was observed in all patients. In urine, significantly higher excretion of vWF fragments was observed in the three diabetic study groups as compared with the controls. In group P the patients' urinary vWF/creatinine levels tended to be higher than in groups N and M. Qualitative analysis of urinary vWF fragments demonstrated a similar distribution pattern of fragments, with three distinctive peaks, in the patients of groups N and M and in the controls. The distribution pattern of vWF fragments in group P, however, differed clearly from that in the controls and showed a great variation within the group. The urinary fragments tended to be of a higher molecular weight and several less distinct fragments with the whole spectrum of molecular weight were observed. Because in these patients with proteinuria no qualitative changes appeared in plasma, it is suggested that abnormal degradation of vWF occurred in the kidneys.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611145 TI - Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control. AB - The impact of metabolic control on the development of rapidly progressive severe retinopathy was studied in 14 young type I insulin-dependent diabetes mellitus (IDDM) patients. Glycosylated hemoglobin (HbAlc) levels 45 months prior to and 12 months after the diagnosis of retinopathy were compared with HbAlc levels in 17 type I IDDM patients with no or minimal background retinopathy, matched for age and duration of diabetes. HbAlc levels were generally higher in patients with severe retinopathy (p less than 0.05) from 39 months until 6 months before the diagnosis of retinopathy. Thereafter, there was a gradual decrease in HbAlc levels reaching the same level as in control patients 6 months after diagnosis of retinopathy. Patients with severe retinopathy required higher doses of insulin prior to the diagnosis of retinopathy (p less than 0.05), but the insulin requirement decreased, and 12 months afterward, the insulin dosage was similar to patients with background retinopathy. Systolic blood pressure levels were slightly increased and higher in patients with severe retinopathy compared with control patients from 18 months before to diagnosis of retinopathy (p less than 0.05). Diastolic blood pressure levels likewise differed at 18 and 12 months before and at the time of diagnosis of retinopathy as well as 12 months afterward (p less than 0.05); however, no differences were seen in urinary albumin or serum creatinine levels between the groups. Thus, years of poor metabolic control, drastically improved, preceded the development of irreversible severe retinopathy in these young type I IDDM patients. PMID- 1611146 TI - Designing multi-viscosity embedding media utilizing novel resin/anhydride/catalyst combinations. PMID- 1611147 TI - New initiatives in quantitative morphology. PMID- 1611148 TI - The blood-testis barrier and Sertoli cell junctions: structural considerations. AB - In this review, a few well-established axioms have been challenged while others were viewed from a new perspective. The extensive literature on the blood-testis barrier has been scrutinized to help probe its mechanics and hopefully to promote understanding of the constant adaptation of the barrier function to germ cell development. Our principal conclusions are as follows: (1) Although the barrier zonule is topographically located at the base of the seminiferous epithelium it actually encircles the apex of the Sertoli cell. Consequently the long irregular processes specialized in holding and shaping the developing germ cells should be considered as apical appendages analogous to microvilli. (2) The development of the barrier zonule does not coincide with the appearance of a particular class of germ cells. (3) The barrier compartmentalizes the epithelium into only two cellular compartments: basal and lumenal. (4) Although the blood-testis barrier does sequester germ cells usually considered antigenic, immunoregulator factors other than the physical barrier seem to be involved in preventing autoimmune orchitis. (5) Structurally, a Sertoli cell junctional complex is composed of occluding, gap, close, and adhering junctions. The Sertoli cell membrane segments facing germ cells are presumably included in the continuum of the Sertoli cell junctional complex that extends all over the lateral and apical Sertoli cell membranes. (6) The modulation (i.e., formation and dismantling) of the junctions in a baso-apical direction is characteristic of the seminiferous epithelium and may be dictated by germ cell differentiation. The formation of tubulobulbar complexes and the following internalization of junction vesicles conceivably represent sequential steps of a single intricate junction elimination process that involves junction membrane segments from different cell types as part of a continual cell membrane recycling system. (7) The preferential association of junctional particles with one or the other fracture-face reflect a response to various stimuli including seasonal breeding. Changes in the affinity of the particles are generally coincidental with cytoskeletal changes. However, changes in the cytoskeleton are not necessarily accompanied by permeability changes. The number of strands seems to reflect neither the junctional permeability nor the transepithelial resistance. The diverse orientation of the strands seems to be related to the plasticity of the Sertoli cell occluding zonule. (8) Cooperation between all constituents (Sertoli cells, myoid cells, cell substratum, and germ cells) of the epithelium seems essential for the barrier zonule to function in synchrony with the germ cell differentiation.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611149 TI - Nickel nitrate: a new junction permeability tracer for the study of the blood testis barrier. AB - With the purpose of evaluating a new intercellular tracer, nickel-K ferrocyanide, we compared results yielded by lanthanum with information provided by nickel. This was done in the seminiferous epithelium of Holtzman rats of several postnatal ages and in a wild local seasonal breeder Galea musteloides. Tissues were studied with transmission electron microscopy and freeze-fracture replications. Nickel tracing proved to delineate cell contours more intensely and less interruptedly than lanthanum. With regard to seasonal variations in adult galea, the limits of the barrier were similar to those described in other mammals: spermatogonia, preleptotene, and leptotene spermatocytes were surrounded by the tracer in the basal compartment. The zygotenepachytenes were contained in the lumenal compartment and tracers were stopped at the inter-Sertoli cell tight junctions. During the inactive spermatogenic phase in winter, the seminiferous epithelium contained Sertoli cells and occasional germ cells, never beyond the spermatocyte stage. The tracer filled intercellular spaces, indicating that the barrier was incompetent. Some resting germ cells showed nuclear hyperchromasia, karyolysis, organelle loss, cell shrinkage, and cell fusion leading to a multinucleated cells. The inter-Sertoli tight junctions were scanty and had randomly oriented and discontinuous junctional strands. Moreover, inter-Sertoli cell gap junctions proliferated. During the active spermatogenic phase in summer, junctions were numerous. Their junctional strands were parallel to each other, and continuous. PMID- 1611150 TI - Effects of vitamin A deficiency on the inter-Sertoli cell tight junctions and on the germ cell population. AB - When 20-day-old rats are placed on a vitamin A deficient diet (VAD) for a period of 10 weeks, the seminiferous tubules are found to contain only Sertoli cells, a few residual A0, A1 spermatogonia, and preleptotene spermatocytes (PL). The type A1 spermatogonia and PL spermatocytes are arrested in their G2 phase. In VAD rats type A2-A4, intermediate (In) and B spermatogonia and all types of spermatocytes (except PL spermatocytes) and spermatids are eliminated from the seminiferous tubules. Two questions were raised in this investigation: 1) Is there, in VAD rats, any correlation between a breakdown of the blood-testis barrier (e.g., Sertoli cell tight junctions) and germ cell loss? 2) Is the disappearance of most germinal cells due to their degeneration during spermatogenesis or to a maturation depletion process resulting from an arrest of spermatogenesis at the spermatogonial stage? To investigate these questions four groups of male Sprague Dawley rats (20-days old) were fed a VAD diet for 7 to 12 weeks. The testes were fixed by perfusion with 2.5% glutaraldehyde in 0.1 M sodium cacodylate containing 2% lanthanum nitrate, an electron opaque tracer used to test the patency of Sertoli cell tight junctions. The lanthanum permeated the intercellular space of the basal compartment but was arrested by normal inter-Sertoli cell tight junctions. The seminiferous epithelium showed numerous degenerating germ cells, some being internalized by Sertoli cells as membrane-bound phagosomes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611151 TI - A personal computer based implementation of the maximum-likelihood method of analysis of electron microscope autoradiographs. AB - The maximum-likelihood (ML) method for the quantitative analysis of electron microscopic autoradiographs has been shown to be substantially superior to the conventional crossfire (CF) method. It can generate reliable and accurate tracer concentration estimates with far fewer micrographs and produce valid estimates even at counts low enough to preclude the use of the crossfire method while eliminating the need for special ad hoc treatment of narrow membranous structures as well as the secondary verification of the tracer concentration estimates. Despite these significant advantages, the large computational requirements of the ML method has to date hampered its widespread use. In this paper, we present a new line-integration method that allows us to reduce the computational requirements of the ML method to a point where it becomes feasible to implement it on a small computer system of the type typically available to a laboratory user of EM autoradiography. We present the complete line-integration method for the particular case of EM autoradiography with tritium, and show how it can be adapted to other isotopes. We have constructed a software package that implements the complete maximum-likelihood method on the IBM PC class of machines using our line-integration method. Features of this software package which are of particular importance to the research community are device independence, which makes it usable with a large variety of currently available laboratory equipment, and easy portability of the software and data between different computer systems. PMID- 1611152 TI - A temperature-jump device for time-resolved cryo-transmission electron microscopy. AB - We describe a temperature-jump device that permits time-resolved studies of thin cryo-transmission electron microscopy specimens. The specimen is rapidly heated to induce a change in microstructure just prior to cryo-fixation. The apparatus consists of a xenon arc lamp equipped with a shutter controlled by timing circuitry, used in conjunction with an environmental specimen preparation chamber. The specimen is heated by exposure to focused light from the lamp, and then plunged into cryogen. Using a thermocouple constructed from an electron microscope grid, we show that temperature jumps of 30-60 K are achieved with exposure times of 150-450 milliseconds. Micrographs of dimyristoyl phosphatidylcholine (DMPC) vesicles and n-docosane films, subjected to these exposures, show that the specimens are still at least 20-30 K above their initial temperature when they contact the cryogen. This method could be applied to a variety of biological and chemical systems which undergo structural changes activated by a rise in temperature. PMID- 1611153 TI - Ras-related GTPases and the cytoskeleton. AB - Incorporation of the available data on rac in neutrophils, CDC42 in yeast, and rho in fibroblasts suggests a general model for the function of rho-like GTPase (Figure 1). Conversion of an inactive cytoplasmic rho-related p21GDP/GDI complex to active p21. GTP occurs by inhibition of GAP and/or stimulation of exchange factors in response to cell signals. p21.GTP is then able to interact with its target at the plasma membrane. This could result in a conformational change in the target, enabling it to bind cytosolic protein(s). Alternatively, p21.GTP could be actively involved in transporting cytosolic protein(s) to the target. A GAP protein, perhaps intrinsic to the complex, would stimulate GTP hydrolysis allowing p21.GDP to dissociate. Solubilization of p21GDP by interaction with GDI would complete a cycle. What about the nature of the final complex? The rac regulated NADPH oxidase complex in neutrophils is currently the best understood and most amenable to further biochemical analysis. Two plasma-membrane bound subunits encode the catalytic function necessary for producing superoxide, but the two cytosolic proteins, p47 and p67, are essential for activity. Why the complexity? Production of superoxide is tightly coordinated with phagocytosis, a membrane process driven by rearrangement of cortical actin. This is not unrelated to the membrane ruffling and macropinocytosis that we observe in fibroblasts microinjected with p21rac. It is tempting to speculate, therefore, that in neutrophils rac is involved not only in promoting the assembly of the NADPH oxidase but also in the coordinate reorganization of cortical actin leading to phagocytosis. For CDC42 controlled bud assembly in yeast, the components of the plasma-membrane complex are not so clear. By analogy with rac in neutrophils, it seems likely that CDC42 is involved in promoting the assembly of cytosolic components at the bud site on the plasma membrane. These putative cytosolic proteins have not yet been identified, but BEM1 and ABP1 are two possible candidates. The biochemical basis for the stimulation of adhesion plaques and actin stress fibers by p21rho in fibroblasts is also unclear. However, components of the adhesion plaque such as vinculin and talin are known to be cytosolic when not complexed with integrin receptors, and rho could be involved in regulating their assembly into the adhesion plaque. Several things are still difficult to incorporate into this model. First the target for CDC42, the bud site, although not yet structurally defined requires the activity of another small GTPase, BUD1. Similarly, in activated neutrophils, the NADPH oxidase is found in a complex with rap1, the mammalian homologue of BUD1 (BoKoch et al., 1989). It seems likely, therefore, that the target is not simply a plasma-membrane protein but may be a complex of proteins whose formation is under the control of the rap1/BUD1 GTPase. The other black box in this model is the actin connection: activation of bud assembly by CDC42 is followed by actin polymerization, activation of NADPH oxidase in neutrophils occurs concomitantly with phagocytosis, a cortical actin dependent process, and p21rho in fibroblasts couples the formation of adhesion plaques to actin stress fibers. One possible link between the GTPase-driven assembly of a plasma-membrane complex and actin polymerization could involve the SH3 domain. Interestingly, both p47 and p67 and yeast ABP1 and BEM1 have SH3 domain. If rho-like GTPases recognize plasma-membrane targets already associated with cortical actin, then this could promote an interaction with a subset of SH3 containing proteins. The result of this would be a GTPase-regulated aggregation of a group of proteins at a single site in the plasma membrane. It is not too difficult to imagine biological processes where such a spatial integration of different biochemical activities would be essential: coupling the assembly of bud components to the formation of actin fibers in yeast; or the activation of NADPH oxidase to phagocytosis in neutrophils; or the assembly of adhesion plaques and the formation of actin stress fibers in fibroblasts are just three examples that have emerged so far. In conclusion, although rho-like GTPases clearly have distinct roles in different mammalian cell types and in yeast, their underlying mechanism of action appears to be strikingly similar. Whether this will remain so when there are some biochemical data to back up these initial observations, time will tell. PMID- 1611155 TI - Treatment of type I diabetes with a combination of glyburide and insulin. AB - OBJECTIVE: To assess the ability of a combination of insulin and an oral hypoglycemic agent (glyburide) to improve the overall glycemic control in a population of patients with type I diabetes. DESIGN: Randomized, placebo controlled, double-blind trial. SETTING: Community-based, university-affiliated, family medicine group. PATIENTS: Men and women between 18 and 68 years of age with type I diabetes. INTERVENTIONS: Subjects were observed and titrated on an insulin-only regimen for 12 weeks (phase I). Subjects were then randomized to receive either placebo or glyburide 10 mg/d for an additional 12 weeks (phase II). MAIN OUTCOME MEASURES: Glucose measurements were taken at breakfast, lunch, supper, and bedtime. Each patient also was followed sequentially for serum lipids, glycosylated hemoglobin, (Hb A1c) and daily insulin utilization. RESULTS: Average fasting blood glucose (FBG) measurements were significantly lower in the glyburide-treated group during phase II (9.22 +/- 0.55 mmol/L) compared with baseline (10.27 +/- 0.93 mmol/L) and phase I (10.41 +/- 0.55 mmol/L). A decrease in the average Hb A1c concentration in the glyburide group was evident by week 4 and was sustained for the duration of the study. The average daily insulin dose rose significantly in the glyburide but not the placebo group compared with baseline. Total cholesterol, triglycerides, and low-density lipoprotein cholesterol did not change significantly in either group over the course of the study. High-density lipoprotein cholesterol increased significantly over baseline in the glyburide group during phase II. Several patients experienced dramatic improvements in glycemic parameters after the addition of glyburide to their insulin regimens. CONCLUSIONS: Improvements were observed in the FBG and Hb A1c measurements of this heterogeneous population of patients with type I diabetes after the addition of glyburide to their insulin regimens. The study failed to find consistent trends in glycemic control when evaluating mean changes in FBG measurements. PMID- 1611154 TI - Double minute chromosomes carrying the human multidrug resistance 1 and 2 genes are generated from the dimerization of submicroscopic circular DNAs in colchicine selected KB carcinoma cells. AB - This study characterizes amplified structures carrying the human multidrug resistance (MDR) genes in colchicine-selected multidrug resistant KB cell lines and strongly supports a model of gene amplification in which small circular extrachromosomal DNA elements generated from contiguous chromosomal DNA regions multimerize to form cytologically detectable double minute chromosomes (DMs). The human MDR1 gene encodes the 170-kDa P-glycoprotein, which is a plasma membrane pump for many structurally unrelated chemotherapeutic drugs. MDR1 and its homolog, MDR2, undergo amplification when KB cells are subjected to stepwise selection in increasing concentrations of colchicine. The structure of the amplification unit at each step of drug selection was characterized using both high-voltage gel electrophoresis and pulsed-field gel electrophoresis (PFGE) techniques. An 890-kb submicroscopic extrachromosomal circular DNA element carrying the MDR1 and MDR2 genes was detected in cell line KB-ChR-8-5-11, the earliest step in drug selection in which conventional Southern/hybridization analyses detected MDR gene amplification. When KB-ChR-8-5-11 was subjected to stepwise increases in colchicine, this circular DNA element dimerized as detected by PFGE with and without digestion with Not 1, which linearizes the 890-kb amplicon. This dimerization process, which also occurred at the next step of colchicine selection, resulted in the formation of cytologically detectable DMs revealed by analysis of Giemsa-stained metaphase spreads. PMID- 1611156 TI - Comparative pharmacodynamics of intravenous lidocaine in patients with acute and chronic ventricular arrhythmias. AB - OBJECTIVE: To evaluate the pharmacodynamics of intravenous lidocaine in patients with acute-onset and chronic ventricular arrhythmias. DESIGN: Open-label, pharmacodynamic evaluation. SETTING: Private, university-affiliated, hospital coronary-care unit. PATIENTS: Twenty cardiac patients with acute-onset ventricular ectopy and 20 with chronic ventricular ectopy. INTERVENTIONS: Intravenous lidocaine was administered to all patients as a 1-mg/kg bolus, a 0.5 mg/kg bolus, and a 2.8-mg/min constant infusion for 48 hours. MAIN OUTCOME MEASURES: Changes in ventricular premature beat (VPB) frequency against total treatment period frequency and by an hour-to-hour assessment of changes in VPB frequency compared with total baseline frequencies. Response was defined as greater than or equal to 80 percent total VPB reduction, greater than or equal to 90 percent paired VPB reduction, and total abolition of nonsustained ventricular tachycardia events. RESULTS: A statistically significant difference in the pharmacodynamic effects of lidocaine were observed during the first eight hours of treatment in patients with acute-onset and chronic VPBs. The number of patients with acute-onset VPBs who responded to lidocaine in the first hour of treatment did not change significantly over the remaining hours of treatment. Response to lidocaine was less in patients with chronic VPBs than in patients with acute-onset VPBs. The response rate to lidocaine was significantly less during the first eight hours in patients with chronic VPBs than in patients with acute-onset VPBs. Following eight hours of treatment, the response rates between acute-onset and chronic VPB patients were not significantly different. Mean lidocaine plasma concentrations were not different between the groups. In addition, there were no significant differences in the incidence of adverse effects between the two groups. CONCLUSIONS: The onset of antiarrhythmic effect as measured by suppression of ventricular ectopy is delayed in patients with chronic VPBs compared with patients with acute-onset VPBs. Decisions about lidocaine response in patients with chronic VPBs cannot be made accurately in the first eight hours of therapy. PMID- 1611157 TI - Possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest. AB - OBJECTIVE: To report a case of possible association of benzalkonium chloride in nebulizer solutions with respiratory arrest and to review the involvement of various preservative agents in paradoxical bronchoconstrictive reactions. DATA SOURCES: Reference articles, case reports, and editorials are identified in the text. DATA SYNTHESIS: Many pharmacologic agents are available for nebulization. In addition to the active drug, these nebulizer solutions may contain preservatives. We describe a case of respiratory arrest in a 64-year-old man following nebulization therapy with albuterol and ipratropium solutions. These solutions contain benzalkonium chloride as a preservative. We are aware of only one report describing two deaths associated with such a severe reaction attributable to nebulization therapy. However, many reports of milder paradoxical bronchoconstriction are available in the medical literature. CONCLUSIONS: Clinicians should be aware of the possibility of paradoxical bronchoconstrictive reactions when patients are treated with nebulized bronchodilators. PMID- 1611158 TI - Loss of seizure control associated with generic substitution of carbamazepine. AB - OBJECTIVE: We report two cases of lost seizure control associated with the generic substitution of carbamazepine, review pertinent literature, and discuss the impact of this substitution on patient care. DATA SOURCES: Case studies, abstracts, and research publications identified in MEDLINE and bibliographic review. DATA EXTRACTION: One author reviewed cases supplied by the other authors and abstracted information from published literature sources. DATA SYNTHESIS: The first case describes a 15-year-old boy who received valproic acid and carbamazepine for partial seizures. A change in government program policies caused him to receive generic carbamazepine. This resulted in loss of seizure control and a decrease in his serum carbamazepine concentration from 12.4 to 6.7 micrograms/mL. When his carbamazepine concentration returned to previous levels, seizure control was not reestablished. A second case involves a 21-year-old woman who substituted generic carbamazepine because of financial problems. After being seizure-free for at least five years on phenobarbital and carbamazepine, she experienced seizures related to the product change. Her carbamazepine concentration decreased from 11.8 to 8.5 micrograms/mL; she also became pregnant at that time. Seizure control was not reestablished. At least three other studies do not support these observations, but the tightly controlled conditions in these studies may not have simulated actual clinical practice. CONCLUSIONS: When generic substitution of carbamazepine is required, serum concentrations should be carefully monitored. The extra care required may negate the financial advantages of the substitution. PMID- 1611159 TI - Hyperkalemia associated with ketorolac. AB - OBJECTIVE: To report and describe the apparent first case of hyperkalemia following intramuscular administration of ketorolac and to discuss the proposed mechanism of action. PATIENT: The patient was a 59-year-old man who developed hyperkalemia following a right upper lobectomy; he had received an intramuscular injection of ketorolac 30 mg for incisional pain. RESULTS: All possible causes of the hyperkalemia, including other drugs and intraoperative and postoperative events, were thoroughly evaluated and ruled out. Hyperkalemia has been reported in patients who have received other nonsteroidal antiinflammatory drugs (NSAIDs). The proposed mechanism of action for the occurrence of this hyperkalemia appears to be related to the suppression of prostaglandin synthesis. CONCLUSIONS: Considering the temporal sequence of events and drugs administered prior to the hyperkalemia in this patient and the hyperkalemic potential associated with other NSAIDs, ketorolac appears to be the precipitating agent. The possibility of hyperkalemia associated with the parenteral use of ketorolac may warrant practitioners to closely monitor the blood chemistry of patients receiving this agent. PMID- 1611161 TI - Treatment of urokinase-related anaphylactoid reaction with intravenous famotidine. AB - OBJECTIVE: We describe our experience with an anaphylactoid reaction to urokinase and the treatment used. We also discuss the use of histamine H1- and H2-blockers in combination for the treatment of allergic anaphylactoid reactions. DESIGN: Case report. SETTING: Hospital. PARTICIPANTS: Observation of a patient who had a pulmonary embolism. INTERVENTION: During the use of urokinase, in treatment of a pulmonary embolism, the patient developed an anaphylactoid reaction that did not respond to diphenhydramine or hydrocortisone. Famotidine was administered. RESULTS: Abatement of urticaria and normalization of vital signs were obtained soon after famotidine was given. Completion of thrombolysis took place. CONCLUSIONS: Further investigation of the use of H1- and H2-blocking agents in the presence of anaphylactoid reactions to thrombolytic agents should be performed. Consideration of intravenous famotidine for the treatment of anaphylactoid-type reactions to urokinase is suggested. PMID- 1611160 TI - Suspected cross-reactivity of enalapril- and captopril-induced hepatotoxicity. AB - OBJECTIVE: To present evidence that enalapril and captopril may produce hepatotoxicity by a common mechanism. DATA SOURCES: A case report and review of pertinent literature. DATA SYNTHESIS: A patient developed hepatotoxicity once while taking enalapril and again while taking captopril. Hepatotoxicity resolved with cessation of therapy. Hepatotoxicity has been reported with use of captopril, enalapril, and lisinopril. Apparent cross-reactivity has been reported on just one other occasion. CONCLUSIONS: Because hepatotoxicity is uncommon with angiotensin-converting enzyme (ACE) inhibitors, our observations suggest the possibility that these agents produce hepatotoxicity by a common mechanism. In patients who develop hepatotoxicity while taking one ACE inhibitor, other agents in this class probably should be avoided. PMID- 1611162 TI - Association of low cholesterol with aggression. PMID- 1611163 TI - Upright tilt-table testing and drug therapy for recurrent vasovagal syncope. PMID- 1611164 TI - Fluconazole: a position statement by the Society of Infectious Diseases Pharmacists. PMID- 1611166 TI - Critical care pharmacy update. PMID- 1611165 TI - Drug- and chemical-induced aseptic meningitis: a review of the literature. AB - OBJECTIVE: The primary objective of this article is to provide readers with case reports of drug- or chemical-induced aseptic meningitis (DCAM) described in the medical literature. Background information regarding the classification of DCAM, incidence, proposed mechanisms, associated risk factors, clinical management, and sequelae is presented. DATA SOURCES: A MEDLINE search was used to identify pertinent background literature and case reports of DCAM. DATA EXTRACTION: All case reports of DCAM involve anecdotal information. A critical analysis of a causal relationship to the implicated drug or chemical and the appearance of meningeal involvement is presented. Animal data are included when pertinent. DATA SYNTHESIS: DCAM is a rare adverse event associated with numerous agents. Patients present with a variety of clinical signs and symptoms and laboratory findings of cerebral spinal fluid, when obtained, vary greatly. Most patients fully recover without sequelae. CONCLUSIONS: Numerous drugs and chemicals have been implicated in the medical literature as producing DCAM. Two proposed mechanisms of DCAM have been theorized: a delayed hypersensitivity-type reaction and direct meningeal irritation. The nonsteroidal antiinflammatory drugs, certain antibiotics, radiographic agents, and muromonab-CD3 have been most frequently implicated. There appears to be an association between the occurrence of the hypersensitivity type reactions and underlying collagen vascular or rheumatologic disease. PMID- 1611167 TI - Hospital nuclear pharmacy--a comparison of physician and pharmacist practice. AB - OBJECTIVE: Nuclear pharmacy is practiced in every hospital with a nuclear medicine clinic. Pharmacists control this practice in fewer than four percent of these institutions. The authors wish to bring to the attention of hospital pharmacists an area of practice in which they can make a significant contribution to the state of pharmacy practice. METHOD: The current state of the physician practice of nuclear pharmacy is described and compared with the accepted standards of pharmacy practice. CONCLUSIONS: Hospital pharmacists can improve pharmaceutical care administered in nuclear medicine by their participation in nuclear pharmacy practice and by the application of hospital pharmacy practice standards. It is also suggested that nuclear pharmacy should be integrated into the pharmacy curriculum at schools of pharmacy. PMID- 1611168 TI - Drug interactions: part II. PMID- 1611169 TI - Characteristics of pharmaceutical opinions written in a Quebec community pharmacy. AB - OBJECTIVE: To describe the characteristics of pharmaceutical opinions written in a community pharmacy and to estimate the possible effects of these opinions on patient drug profiles. DESIGN: Retrospective survey. SETTING: The community pharmacy where these opinions were written is located in a rural area of the province of Quebec. Only health-related items are sold and no merchandise is displayed in this pharmacy. PARTICIPANTS: Ten pharmacists worked at this pharmacy during the period of the study. INTERVENTION: Pharmacists were paid when they sent advice to a patient or a physician about the patient's drug profile or about the therapeutic value of a prescribed treatment. This survey included recommendations made from 1978 to 1983. A sample of 600 opinions was drawn at random from a total of 1992 opinions that had been written at the site of the study. MAIN OUTCOME MEASURE: The impact of each opinion was assessed by analyzing patient drug profiles for three months after the opinion was written to determine if the recipient had followed the pharmacist's recommendation. RESULTS: Pharmacists, on their own initiative, sent 97.9 percent of the opinions. Only 1.7 percent of the opinions were requested by patients and 0.4 percent by physicians. Most opinions were addressed to patients (86.7 percent) rather than to physicians (13.3 percent). Almost four of five recommendations sent to patients were about compliance (45.1 percent) or were suggestions for improving the therapeutic effect of a medication or replacing a drug with nondrug treatment (33.4 percent). The three most common recommendations sent to prescribers were to replace one drug with another (25 percent), to change the dose or dosing schedule of a drug (16.3 percent), and to discontinue drug treatment (16.3 percent). Chemical stability, underuse or overuse of a medication, and adverse effects were the most frequent causes of recommendations sent to patients. Adverse effects, interactions, and the underuse of a medication were the most frequent reasons for recommendations sent to physicians. The proportion of recommendations that were implemented was 77.7 percent for patients and 58.1 percent for physicians. CONCLUSIONS: The pharmaceutical opinion seemed to be a good means of communicating with patients and prescribers on a wide variety of problems encountered in a community pharmacy. It allowed pharmacists to be paid for their expertise even if a drug was not dispensed. Also, the pharmaceutical opinion could compensate for the loss of income when the pharmacist recommended replacing a prescribed medicine with nondrug treatment. PMID- 1611170 TI - Fluconazole therapy in a child with Candida tropicalis fungemia. PMID- 1611171 TI - Interaction between isoniazid and carbamazepine potentiated by cimetidine. PMID- 1611173 TI - Comment: high-dose phenylephrine infusion. PMID- 1611172 TI - Nonalcohol-based chlorhexidine dental rinse. PMID- 1611174 TI - Comment: medical versus pharmaceutical continuing education. PMID- 1611175 TI - No AIDS risk from polio vaccines. PMID- 1611176 TI - Compliance policy guide addresses prescription drug compounding. PMID- 1611177 TI - New drug initiatives announced. PMID- 1611178 TI - Identical 24-hour intragastric pH response to low continuous infusion doses of famotidine in active gastric ulcer patients. AB - In order to establish the therapeutic plasma concentration of famotidine, the 24 h intragastric pH response to low-dose intravenous (i.v.) continuous infusion of 40 (group A) or 20 mg/day (group B), administered over more than two days, was studied in 10 adult patients with active gastric ulcers (GU). In group A, the mean age was 64.8 years and in group B, 54.2 years. On the second day, 4 blood samples were collected for famotidine assay and 24 h intragastric pH monitoring was performed. RESULTS: the mean 24 h pH did not differ significantly (P less than 0.01) between group A at 6.9 and group B at 7.2. In group A, the percentage of time with pH above 6.0 and above 7.0 were 94.8 and 59.0, respectively, and the mean famotidine dose and plasma concentration were 0.81 mg/kg/day and 140.89 ng/ml. In group B, the percentage of time with pH above 6.0 and 7.0 were 97.6 and 65.4, and the mean dose and famotidine concentration were 0.34 mg/kg/day and 45.42 ng/ml. In conclusion, in fasting patients with active gastric body ulcers, continuous infusions of low-dose famotidine maintain both the therapeutic plasmatic concentration and the intragastric pH to near anacidity level. PMID- 1611179 TI - Prognosis of patients with congestive heart failure: its determinants in various heart diseases in Japan. AB - We investigated the prognosis of patients with congestive heart failure (CHF) and the factors which influence the prognosis of Japanese patients with this condition. From among the patients admitted to our hospital from January 1, 1978 to December 31, 1985, the 298 patients who were diagnosed having CHF were investigated. Patients with CHF had a rather poor prognosis, with the 1-year, 3 year, and 5-year cumulative survival rates being 76%, 60%, and 49%, respectively. The factors influencing the prognosis of patients with CHF were the type of underlying heart disease, the left ventricular ejection fraction, the left ventricular end-diastolic dimension, and the central venous pressure. Survival rates differed significantly depending on the type of underlying heart disease. The cumulative 5-year survival rate was 35% for coronary artery disease, 40% for dilated cardiomyopathy, 53% for rheumatic valvular heart disease, and 80% for hypertensive heart disease. PMID- 1611180 TI - Efficacy of ivermectin against Strongyloides stercoralis in humans. AB - Okinawa Prefecture is an endemic area of Strongyloides stercoralis infection. Since treatment of this infection remains unsatisfactory, we evaluated the efficacy of ivermectin. Twenty-three patients were treated with a single oral dose of ivermectin (mean +/- SD, 105.5 +/- 20.8 mcg/kg of body weight), followed by a second dose two weeks later. The rate of cure was 85.7% at 2 weeks after the first treatment, and 90.5% at 2 weeks after the second treatment. Side effects occurred in 2 patients (8.7%), but they were mild and transient. The results indicate that ivermectin might be useful and relatively safe for the therapy of Strongyloides stercoralis infection as an alternative to thiabendazole or mebendazole. PMID- 1611181 TI - Prophylactic use of ofloxacin in granulocytopenic patients with hematological malignancies during post-remission chemotherapy. AB - The prophylactic efficacy of ofloxacin (OFLX) therapy was evaluated in 51 granulocytopenic episodes in 22 patients with hematological malignancies during post-remission chemotherapy in a prospective, randomized, controlled trial. Oral administration of OFLX plus amphotericin-B (AMPH) and polymyxin-B (PL) reduced episodes of fever and infection more than did the control regimen with PL and AMPH alone (p less than 0.01), and the reduction in the incidence of infection was evident even in patients showing severe granulocytopenia (p less than 0.01). Furthermore, the first fever after the onset of granulocytopenia in the OFLX regimen developed later than that in the control regimen (p less than 0.05). Clinically, the prophylactic efficacy was 92% for the OFLX regimen and 40% for the control regimen (p less than 0.01). These findings suggest that OFLX is a promising prophylactic agent following post-remission chemotherapy. Patient hemomyelogram findings similar to those of patients with other malignancies may imply that OFLX is widely effective in granulocytopenic patients taking aggressive chemotherapy. PMID- 1611182 TI - Reinfusion of autogenous ascitic fluid concentrated by freezing in patients with intractable ascites. AB - Eleven patients with intractable ascites were treated by intravenous reinfusion of concentrated autogenous ascitic fluid. The ascitic fluid was drained and centrifuged for removal of cells by a cell separator. Cell-free ascitic fluid was frozen in a medical freezer at -15 degrees C and thawed at room temperature. The fraction at the initial stage of melting contains a high concentration of protein and was thus collected and reinfused to the patient. In this initial fraction, the recovery rate of albumin was 42.0 +/- 9.0% and the concentration of protein was 7.1 +/- 2.4 g/dl. This frozen method is inexpensive and time saving, because it does not use a filter. Ascites was ameliorated in all patients with 1 to 19 times of reinfusion. Therefore, when renal function is not disturbed, the frozen method may be indicated for management of intractable ascites. PMID- 1611183 TI - Cellular composition of fluid in the airways of patients with house dust sensitive asthma, classified by clinical symptoms. AB - The cellular composition of bronchoalveolar lavage (BAL) fluid was observed in 28 patients with house dust mite-sensitive asthma. The proportion of neutrophils in the BAL fluid was significantly higher in the patients between the ages of 50 and 59 and those over 60 than in the patients younger than age 39. There was a significant difference in the number of neutrophils in patients aged 30-39 years and in those over 40 at the onset of disease. The cellular composition varied among the three types of asthma; the mean percentage of cells in the BAL fluid was 1.1% neutrophils and 21.3% eosinophils in type Ia (simple bronchoconstriction), 9.1% neutrophils and 23.0% eosinophils in type Ib (bronchoconstriction + hypersecretion), and 34.4% neutrophils and 12.0% eosinophils in type II (bronchiolar obstruction). The results suggested that an increased frequency of both neutrophils and eosinophils correlates with the mechanism of hypersecretion, and that a marked increase in the proportion of neutrophils is involved in bronchiolar obstruction. PMID- 1611184 TI - Human myeloma cell line (KHM-4) established from a patient with multiple myeloma associated with hyperammonemia. AB - A cell line of plasma cells with high ammonia (NH3) production (KHM-4) was established from a patient with multiple myeloma complicated by hyperammonemia and abnormal serum concentrations of amino acids. Surface marker studies of KHM-4 cells showed that the cells were positive for cytoplasmic immunoglobulins (IgA kappa), HLA-DR, and T 10. Secretion of ammonia by the KHM-4 cells was detected by the addition of L-glutamine and L-arginine into the culture medium of amino acid free RPMI 1640. In the presence of L-glutamine, KHM-4 cells secreted a greater amount of ammonia than the T cell line, CEM. However, production of ammonia by L arginine was not observed in other cell lines. These observations provide evidence for the existence of a peculiar amino acid metabolism in the myeloma cells causing hyperammonemia and serum amino acid disturbance. PMID- 1611185 TI - Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy. AB - Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters. PMID- 1611186 TI - Multiple sclerosis in Hokkaido, the northernmost island of Japan: prospective analyses of clinical features. AB - We analyzed the clinical features of multiple sclerosis (MS) prospectively seen between July 1986 and October 1989 on Hokkaido island, the northernmost part of Japan. Clinical features were generally considered to be intermediate between the previous Japanese reports and those of Western countries. Devic's disease was rare and simultaneous bilateral visual loss at on set was not too common this series, differing from that previously reported of Japanese MS. The high incidence of acute transverse myelopathy and lesser involvement of the cerebellum, however, support the previous view. Further clinical and epidemiological studies will be necessary on this island. PMID- 1611187 TI - A familial case of hereditary angioneurotic edema in Japan. AB - A 53-year-old man was admitted with impairment of breathing following laryngeal edema. Serum levels of CH50 (22 U/ml), C4 (3 mg/dl), C1-INH protein (10.6 mg/dl) and C1-INH activity (LT 25%) were low. Complement study of the patient's family members revealed that he was one of 5 patients in 3 generations with hereditary angioneurotic edema (HANE). Administration of the androgen derivatives Danazol (600 mg/day) and Oxymetholone (30 mg/day) effectively increased serum levels of C1-INH activity and C4. Though eruption and hepatic dysfunction attributable to administration of the drugs appeared, these side effects improved after withdrawal of the drugs. Subsequently, the treatment with Danazol at a low dose (100 mg/day) was resumed, and the patient has had no episodes of edema for the past 3 years. Regarding the familial cases of HANE, fewer than 20 have been reported in Japan. PMID- 1611188 TI - A variant serum cholinesterase and a confirmed point mutation at Gly-365 to Arg found in a patient with liver cirrhosis. AB - A 64-year-old man was admitted to our hospital because of possible liver cirrhosis. His serum cholinesterase was anomalously low with a delta pH of 0.1 (normal range; 0.8-1.1). His enzyme was more heat-labile than the normal controls. Km value of his enzyme for benzoylcholine was 1.1 x 10(-5) mol/l, while that for normal controls was 2.3 x 10(-6) mol/l. In addition, isozymic alteration of his enzyme was observed. Sequencing of the white blood cell DNA of the patient showed a point mutation at nucleotide 1093 (GGA to CGA), which changes codon 365 from glycine to arginine. PMID- 1611189 TI - Two cases of hypothyroidism associated with alpha-interferon therapy. AB - Alpha-interferon was used for anti-cancer or anti-viral therapy in two patients with preexisting autoimmune thyroid disease and in seven patients with chronic viral hepatitis who had no history of thyroid dysfunction. Primary hypothyroidism developed in the two patients who had a history of autoimmune thyroid disease, while no changes in thyroid function were observed in the other seven patients. Modulation of the immune system by alpha-interferon may have been responsible for the development of hypothyroidism in these two patients. Therefore, autoantibodies to the thyroid and the thyroid function should be assessed in patients undergoing alpha-interferon therapy. PMID- 1611190 TI - Lactate dehydrogenase (LDH)-linked immunoglobulin in a patient with Graves' disease treated with methimazole. AB - A 26-year-old woman who received methimazole treatment for Graves' disease is discussed. Two months following treatment, her serum GOT level rose to 45 K.U, her GPT to 60 K.U, and her lactate dehydrogenase (LDH) to 645 W.U; a hepatic disorder was then suspected. Later, the serum GOT and GPT concentrations decreased to a normal range, but her serum LDH continued to maintain a high level. An LDH isoenzyme analysis showed an abnormally broad LDH. The IgG that was linked to the LDH is suspected to have been the result of her underlying autoimmunity, the methimazole treatment, and the development of her hepatic disorder. Thus, this IgG was thought to be the autoantibody to LDH. PMID- 1611191 TI - A case of congenital dyserythropoietic anemia type II associated with hemochromatosis. AB - A 54-year-old woman with anemia, diabetes mellitus and liver dysfunction was admitted to our hospital. Numerous binucleated erythroblasts in the bone marrow, a positive serum acidified test, and the presence of anti I and anti i antigens on the surface of her erythrocytes indicated that she had congenital dyserythropoietic anemia (CDA) Type II. Hemochromatosis was confirmed by a liver biopsy. This case is a sibling of a patient with CDA Type II reported by Omine et al in 1981 (Acta Haematol Jpn 44:1). They report that no physical or hematological abnormalities were found when she was examined at the age of 29 years. Twenty-five years later, she developed CDA Type II and hemochromatosis. This case indicates that long-term observation of the family members of a patient with CDA Type II is necessary. PMID- 1611192 TI - A case of Cushing's syndrome associated with chronic respiratory failure due to metabolic alkalosis. AB - A case of Cushing's syndrome associated with chronic respiratory failure is presented. Although arterial blood gas analysis showed severe metabolic alkalosis, hypoxemia and mild hypercapnia, the patient had no evidence of pulmonary disease or neuromuscular disorder. Voluntary hyperventilation and inhalation of 100% oxygen (O2) revealed normalized arterial oxygen tension (PaO2). Following the recovery from metabolic alkalosis by the treatment with potassium chloride, PaO2 was elevated and arterial carbon dioxide tension (PaCO2) was lowered. Therefore, it was strongly suggested that the main cause of chronic respiratory failure was compensatory alveolar hypoventilation as a response to metabolic alkalosis. PMID- 1611193 TI - Chronic eosinophilic pneumonia with small abscesses in the tracheo-bronchial mucosa and lung parenchyma. AB - Abscess formation is uncommon in eosinophilic lung disease. In this paper we present a case of chronic eosinophilic pneumonia in which bronchofiberoscopy revealed scattered small abscesses in the large airways. Pathological examination revealed the presence of inflammatory cells with eosinophilic infiltration in both the bronchial mucosa and lung parenchyma. PMID- 1611195 TI - Family of a patient with serum cholinesterase deficiency. AB - A-39-year-old man was admitted to our hospital because of a markedly decreased level of serum cholinesterase found incidentally by a blood test. Detailed examination did not reveal severe liver disease, malignant tumor, infection or organophosphate compound poisoning. Investigation of three generations of his family revealed two homozygous and five heterozygous family members with the cholinesterase deficiency gene E1s indicating familial serum cholinesterase deficiency. PMID- 1611194 TI - Magnetic resonance imaging of the hypoplasia of the rhinencephalon in a patient with Kallmann's syndrome. AB - A patient with hypogonadotropic hypogonadism and anosmia (Kallmann's syndrome) is described. Anosmia has been believed to be due to hypoplasia of the rhinencephalon. This anatomical defect was demonstrated in vivo in a patient with Kallmann's syndrome by magnetic resonance imaging (MRI). PMID- 1611196 TI - Magnetic resonance imaging for the diagnosis of esophago-aneurysmal fistula. AB - A 77-year-old woman who complained of dysphagia was found to have an aneurysm in the descending aorta. Magnetic resonance imaging (MRI) demonstrated the state of thrombi, a thin and irregular soft tissue signal between the aneurysm and the esophagus, which suggested an esophago-aneurysmal fistula revealed by the operation. MRI was effective in the evaluation of the status of aneurysm. PMID- 1611197 TI - Cyclosporin for inflammatory pseudotumour. AB - Dramatic efficacy of cyclosporin was observed in a patient with inflammatory pseudotumour in the liver. The 30-year-old male patient had suffered several attacks of high fever, polyarthralgia and lymph node swelling since 1981. In February 1989, abdominal CT showed multiple space-occupying lesions in his liver, and histopathology of the biopsied liver showed infiltration of plasma cells and lymphocytes with proliferation of collagen fiber, which was comparable to an inflammatory pseudotumour. In May 1990, a treatment regimen of cyclosporin A along with prednisolone was begun because he had been diabetic since March 1990. Within a few days of treatment, the high fever and polyarthralgia subsided, and leucocytosis of 32,000/mm3 and the increased CRP of 17.7 mg/dl were normalised within one month. A reduction of the size of the space-occupying lesions in the liver was observed on abdominal CT taken one month after cyclosporin treatment. PMID- 1611198 TI - A case of idiopathic retroperitoneal fibrosis with chronic pericarditis. AB - A 66-year-old male with chronic pericarditis accompanied by idiopathic retroperitoneal fibrosis was originally admitted for cardiac tamponade. A firm diagnosis was obtained only after the patient's sudden death when autopsy was performed. Chest X-rays showed cardiac enlargement and pleural effusion. Echocardiogram revealed bright echo density on the myocardium. PMID- 1611199 TI - A case of primary biliary cirrhosis associated with Hashimoto's thyroiditis, scleroderma and Sjogren's syndrome. AB - A 53-year-old woman was admitted because of Raynaud's phenomenon, polyarthralgia and polymyalgia. Biopsy specimens of the liver and thyroid gland revealed characteristic findings of primary biliary cirrhosis (PBC) (stage I by Scheuer's classification) and chronic thyroiditis. Her clinical features were also complicated by scleroderma (type I by Barnett's classification) and Sjogren's syndrome (Sjs) with keratoconjunctivitis sicca. Thyroid hormone replacement therapy led to improvement in thyroid function, normalization of the biliary tract enzymes and alleviation of subjective symptoms. PMID- 1611200 TI - Interstitial lattice shadow and mediastinal lymphadenopathy with an elevation of carcinoembryonic antigen in severe pulmonary alveolar proteinosis. AB - A case of severe pulmonary alveolar proteinosis (PAP) with interstitial involvement, mediastinal lymphadenopathy and an elevation of carcinoembryonic antigen (CEA) in the bronchoalveolar lavage (BAL) fluid and the serum is presented. Alveolar macrophages may play a major role in these rare and seemingly unrelated findings. PMID- 1611201 TI - Microangiopathic hemolytic anemia in a graft-versus-host disease patient treated with cyclosporine A and prednisolone. AB - A 38-year-old male patient with chronic myelocytic leukemia in the first chronic phase underwent bone marrow transplantation (BMT) from an HLA identical sibling. He developed chronic graft-versus-host disease and his condition gradually deteriorated. Fourteen months after BMT, acute progressive anemia, thrombocytopenia, reticulocytosis, increased serum lactic dehydrogenase and increased serum bilirubin were revealed following treatment with cyclosporine A (240 mg/day i.v.), prednisolone (60 mg/day i.v.) and azathioprine (100 mg/day p.o.). Red blood cell fragmentations were also found microscopically. At that time, the serum cyclosporine A trough level was 1,300 ng/ml by the polyclonal antibody RIA method. These symptoms were resolved by discontinuation of cyclosporine A and administrations of aspirin, cilostazol, and dipyridamole as anti-platelet agents. We consider this phenomenon to be micro-angiopathic hemolytic anemia due to a serum high cyclosporine A level which resulted from the concomitant use of cyclosporine A with prednisolone. PMID- 1611202 TI - Plasma free catecholamine level during hemopurification in a case of pheochromocytoma. AB - To examine the alteration of the plasma free-catecholamine level during hemopurification in a patient with pheochromocytoma, the levels of plasma free catecholamine and total catecholamine in the filtrate were monitored pre- and post-hemopurification. Approximately 100 micrograms of total catecholamine was removed by the hemopurification procedure though the high level of plasma-free catecholamine remained unaltered. PMID- 1611203 TI - Taxonomy of Campylobacter, Arcobacter, and Helicobacter: a review. PMID- 1611205 TI - Characteristics of bovine Staphylococcus aureus with special regard to clumping factor activity. AB - The occurrence of the following groups of bovine Staphylococcus aureus with characteristic patterns of biochemical reactions and sensitivities to phages was confirmed by the present investigation of 662 isolates from the udders of cows in 53 dairy herds: (1) host-specific variety (v) bovis, (2) not alloted strains with the basic marker, crystal violet type A (group na CV A), (3) group na CV C. The latter was split into three subgroups clearly differing in phage susceptibility patterns: I/119, I without 119 and III, respectively. Lack of clumping factor activity occurred in 323 out of 346 (93%) phage pattern I/119 strains examined while most or all isolates of the other groups of bovine strains proved to be clumping-positive. PMID- 1611204 TI - Characterization of Borrelia burgdorferi glycoconjugates and surface carbohydrates. AB - Borrelia burgdorferi glycoconjugates with different oligosaccharide structures were characterized by a blotting technique with peroxidase-labelled lectins. The localization of surface carbohydrates was studied using electron microscopy with lectin-gold complexes. A high-mannose glycan structure was detected in 83 kDa glycoprotein (major extracellular protein); at least four carbohydrates (glucose or mannose, galactose, N-acetylgalactosamine and N-acetylglucosamine) were present in other Borrelia glycoconjugates. N-acetylneuraminic (sialic) acid was detected on the Borrelia surface. Two sialidases with different specificities were used in an attempt to cleave off the Borrelia N-acetylneuraminic acid. The attempt was successful by using Vibrio cholerae sialidase which has a broad substrate specificity, while the mumps-virus sialidase with restricted substrate specificity had no effect. Endogenous activity of N-acetylneuraminidase was not demonstrated in B. burgdorferi K 5 and B 31 strains. PMID- 1611206 TI - The use of radiometric tests in the speciation of mycobacteria--a review. AB - Besides a more rapid detection and susceptibility testing, radiometry offers possibilities for the identification of mycobacteria. This paper gives a chronological summary of radiometric techniques used in the BACTEC system (Becton Dickinson) for the identification of mycobacterial complexes/species, employing chemical compounds as selective inhibitory agents or for testing biochemical activities. Thirteen tests are presented and discussed. PMID- 1611207 TI - Cytometric haematological analysis of experimental Yersinia pseudotuberculosis infection at temperatures of cultivation of 25 degrees C and 37 degrees C. AB - The dynamics of acute lethal infection with Yersinia pseudotuberculosis (serovar III) grown at 25 degrees C and 37 degrees C, respectively, were studied in guinea pigs. Using an automated hematology analyzer, the quantity and quality of the host cellular response was determined at the primary site of infection (the peritoneal cavity) and in parallel in the blood. A much more intensive leucocytic response of monocytic type was observed in the animals infected with microorganism grown at 37 degrees C. This type of reaction was associated with a lower mortality rate and a relatively benign progression of the infection. PMID- 1611209 TI - Etiology and antibiotic susceptibility of bloodstream Streptococcus sp. AB - 249 episodes of Streptococcus bacteraemia in hospitalized patients were evaluated for both clinical and microbiological features. Specification of the isolates demonstrated that infective endocarditis was predominantly associated with Streptococcus sanguis and Streptococcus bovis whereas Streptococcus pyogenes and Streptococcus milleri were the most common cause of local and/or systemic infections. In vitro-susceptibility tests towards 9 selected antibiotics proved that beta-lactam antibiotics are potent compounds for the treatment of Streptococcus sp. with the exception of enterococci; that ampicillin turned out to be highly effective against enterococci; and that vancomycin may be regarded as a potent alternative in the treatment of streptococcal infections. PMID- 1611208 TI - Activity of antimicrobial agents against Mycobacterium avium-intracellulare complex (MAC) strains isolated in Italy from AIDS-patients. AB - Twenty-five strains of Mycobacterium avium-intracellulare (MAC) isolated from acquired immunodeficiency syndrome (AIDS) patients in three medical centres in Italy have been studied. Serotyping performed on eighteen strains showed various serovars within either M. avium or M. intracellulare serotypes and with serovars 1 and 21 being the most prevalent (four strains for each serovar). Among fourteen drugs used for testing the antibiotic sensitivity, rifapentine, rifabutin and clofazimine showed to have the best in vitro activity. In an ex vivo model of infection using peritoneal resting macrophages from the C57BL/6 mouse, the intracellular viability of a strain of M. avium (strain 489, serovar 3) was reduced by clofazimine, amikacin, ciprofloxacin, rifabutin and clarithromycin (99, 98, 93, 89 and 69%, respectively), thus indicating for clofazimine a good correlation between in vitro and ex vivo activity. PMID- 1611210 TI - Delayed type hypersensitivity (DTH): studies on necrotising DTH-reactions against listerial antigen in the skin of guinea pigs. AB - Delayed type hypersensitivity (DTH) to facultative intracellular bacteria which leads to destructive skin reactions was so far only investigated against mycobacterial antigens in guinea pigs whereas this work investigates destructive DTH-reactions in the skin of guinea pigs which are directed against listerial antigens. Toxic factors of viable listerias induced an enhancement of destructive skin reactions in non-immunised guinea pigs as compared to immunised ones. In contrast, heat killed listerias (HKL) induced necrotising skin reactions in immunised and non-immunised guinea pigs which were significantly enhanced by DTH in immunised guinea pigs. 5 days after immunisation, necrotising reactivity was maximal and increased in a dose-dependent mode with higher amounts of HKL. Listeria-specific T-cells were able to interact specifically with allogeneic macrophages in vitro. By means of adoptive transfer of listeria-specific T-cells it was possible to transfer successfully Listeria-specific DTH-reactivity from immunised donors to non-immunised recipients. PMID- 1611211 TI - Coincidence of hepatitis B-virus markers and other sexually transmitted diseases in different STD-risk groups. AB - To evaluate the prevalence of hepatitis-B-virus (HBV)-markers in STD patients and the significance of promiscuous heterosexual activity as a risk factor for the transmission of HBV, a serological screening was performed in 499 patients, in addition to the routine STD diagnostic programme. Two groups of patients were evaluated: group 1 (120 patients) was drawn from the STD clinic of the Public Health Office (PHO), group 2 (379 patients) from a private STD outpatient clinic. Promiscuous activity was reported significantly more often by persons of group 1 than by those attending the private clinic (59.3% vs. 5.1%). The infection rate of gonorrhea, syphilis and Chlamydia trachomatis was high in patients of the PHO (46.7%, 35.3%, 27.5%) whereas most of the STDs were seldom ascertained in patients of the private clinic (1.1%, 0%, 5.6%). Similar to other STDs, the prevalence of HBV markers differed significantly between patients of the PHO and those of the private clinic (33.3% vs. 6.3%; p = .0000). Comparison of HBV and other STDs showed the highest coincidence of HBV markers in patients with serological evidence of syphilis (44.2%), and in one third of patients with Neisseria gonorrhoeae as well as HIV infection. The data obtained in the present study demonstrate that also in Austria, in addition to homosexual preference and drug abuse, promiscuous heterosexual activity must be considered a substantial risk factor for the transmission of HBV. PMID- 1611212 TI - [Isolation and identification of Micrococcaceae, especially the genus Staphylococcus]. PMID- 1611213 TI - The mouse pink-eyed dilution locus: a model for aspects of Prader-Willi syndrome, Angelman syndrome, and a form of hypomelanosis of Ito. AB - The region of mouse Chromosome (Chr) 7 containing the mouse pink-eyed dilution locus, p, is syntenic with human chromosome 15q11-q13, a region associated with three human syndromes, Prader-Willi syndrome (PWS), Angelman syndrome (AS), and a form of hypomelanosis of Ito (HI). Because some mutant alleles of p also share a subset of phenotypes with PWS, AS, and HI, the same gene or genes disrupted by p locus mutations are potentially involved in the phenotypes of PWS, AS, and HI. PMID- 1611214 TI - PCR-analyzed microsatellites of the mouse genome--additional polymorphisms among ten inbred mouse strains. AB - Eighty sequences from the mouse genome database containing microsatellites (simple sequence repeats) have been analyzed for size variation among ten different inbred strains of mice; 62/80 (77.5%) showed polymorphism of at least three alleles. We have been able to detect all the polymorphisms by agarose gel electrophoresis, often running the gels for up to 3 h. Between individual pairs of mouse strains to be used in chromosomal mapping studies in our laboratory, 35 60% polymorphism occurred. There are potentially enough microsatellites within the mouse and human genome to have a marker at every 1-cM distance. This simple approach will, therefore, continue to be useful in genome mapping studies, leading eventually to high-resolution maps of both the mouse and human genomes; this should allow for physical mapping and cloning of specific genes. PMID- 1611215 TI - Evolution of a B2 tagged sequence from a long-range repeat family in the genus Mus. AB - A long-range repeat family of more than 50 kb repeat size is clustered in Chromosomes (Chr) 1 of Mus musculus and M. spretus. In M. musculus this long range repeat family shows considerable variation of copy-number frequency and contains coding regions for at least two genes. In an intron of a gene, which is part of the repeat, a B2 small interspersed repetitive element (SINE) is inserted at identical positions. The B2 element is present in all copies of the long-range repeat family; it was presumably a component of the ancestral single-copy precursor sequence that gave rise by amplification to the repeat family. Copies of the long-range repeat family vary with respect to the number of TAAA tandem repeats in the A-rich 3' end region of the B2 element. As inferred from polymerase chain reaction (PCR) data, presence and frequency of repeat number variants in the (TAAA)n block are strain and species specific. The B2 element and its flanking regions were sequenced from two copies of the long-range repeat family. Sequence divergence between the two copies (only non-CG base substitutions and deletions/insertions) was determined to be 2.6%. Based on the drift rate in human Alu elements and a correction for the higher drift rates in rodents, an estimate for the divergence time of 1.7 million years was calculated. Since the long-range repeat family is present in M. musculus and M. spretus, it must have evolved by amplification before the separation of the two species about 1-4 million years ago. PMID- 1611216 TI - The structure of the mouse parvalbumin gene. AB - Parvalbumin (PV) is a calcium-binding protein of the EF-hand family, expressed mainly in fast contracting/relaxing muscles of vertebrates. We have isolated five overlapping genomic PV clones which overall span 28 kilobase pairs (kb) around the Pva locus on mouse Chromosome (Chr) 15. The positions of four introns were determined by DNA sequencing. They interrupt the coding sequences at positions corresponding to those in rat and human PV genes. The transcription start site, 25 bp downstream from the TATA-box, was mapped by oligonucleotide primer extension on poly(A)(+)-RNA. The analysis of 0.4 kb promoter sequence of the mouse PV gene revealed CCAAT- and TATA-box sequences and a 59 bp GC-rich stretch between positions -59 and -118. Similar motifs have been found in the parvalbumin genes of rat and human. A perfect 11-bp repeat upstream to positions -149 and 163 respectively is homologous only to the rat promoter. These results will be related to tissue and species differences in PV expression. PMID- 1611217 TI - Nucleotide sequence and genomic organization of a tandem satellite array from the rock vole Microtus chrotorrhinus (Rodentia). AB - A tandem satellite array (herein named MSAT-160) has been isolated and characterized from the rodent Microtus chrotorrhinus. Sequence data from 15 partial or complete monomers revealed a repeat unit length of 160 bp. This unit length was apparently derived from two shorter sub-motifs, one a tetramer (GAAA), the other a hexamer (CTTTCT), through polymerase slippage and mutation. Collectively, perfect or imperfect variants of these two motifs comprise nearly 60% of the component. Southern blot analyses of genomic DNA digested with 14 different restriction endonucleases indicated that most enzymes yielded either classical type A or type B restriction patterns, while RsaI yielded a pattern that combined features of both the A and B types, and BamHI appeared to lack sites altogether in MSAT-160. An examination of restriction patterns from 16 individuals with three enzymes failed to identify intraspecific variation, while a related study compared 11 species and documented interspecific distinctiveness (Modi, submitted). Fluorescence in situ hybridization indicated that the satellite DNA was located at the centromeres of several autosomes and at sex chromosome heterochromatin. PMID- 1611218 TI - The murine even-skipped-like gene Evx-2 is closely linked to the Hox-4 complex, but is transcribed in the opposite direction. PMID- 1611219 TI - Quality of life and vertebral osteoporosis. PMID- 1611220 TI - Osteoporosis: the evolution of a scientific term. AB - Coined in French in the early 1820s as a mere description of a pathological state of the bone, the term 'osteoporosis' made its way into the English medical vocabulary only in the twentieth century. Unlike other medical concepts, which have not been substantially altered by progress in medical research, the definition of osteoporosis has constantly reflected the state of knowledge on the phenomenon itself. Over its 170 years of evolution, this definition has continuously sought to maintain a difficult balance between physiological and clinical criteria. Even at present, while the 1990 Consensus Conference definition (centering mainly on physiological deterioration) merely implies the clinical aspect through the notions of fragility and fracture risk, others advocate restriction of the term to the clinical consequences of osteopenia. How will the concept of osteoporosis develop in the future? This article, which deals with the origin of the term and its successive definitions, is offered as a basis for further discussion on this subject of high topicality. PMID- 1611221 TI - The effects of calcium supplementation and exercise on bone density in elderly Chinese women. AB - A randomized controlled trial was carried out to determine whether calcium supplementation and load-bearing exercise can increase or maintain bone mass in the elderly. Fifty Chinese women, aged 62-92 years, living in a hostel for the elderly in Hong Kong were randomized to enter one of four treatment groups: (I) calcium supplementation of 800 mg (as calcium lactate gluconate) daily; (II) load bearing exercise four times a week plus a daily placebo tablet; (III) calcium supplementation daily and load-bearing exercise four times a week; (IV) a placebo tablet daily. The interventions went on for 10 months. The bone mineral density (BMD) was measured at three sites in the hip (femoral neck, Ward's triangle and intertrochanteric area) and the L2-4 level of the spine. The percentage change in BMD in 10 months was used as the main outcome measurement. The parathyroid hormone level and indices of bone metabolism were also measured before and after 10 months of intervention. The BMD at Ward's triangle and the intertrochanteric area increased significantly in subjects on calcium supplement (p less than 0.05), but there was no significant change at the spine and femoral neck. Exercise had no effect on bone loss at any site. However, the results of two-way analysis of variance showed a significant joint effect of calcium supplements and exercise at the femoral neck (p less than 0.05), but not at the other sites. The parathyroid hormone levels fell significantly in subjects on calcium supplements (p less than 0.01). Calcium supplement in the form of calcium lactate gluconate was adequately absorbed in elderly Chinese women with a calcium intake of less than 300 mg per day. It was effective in reducing bone loss at the hip, and there may be interaction effects with exercise in maintaining bone density. PMID- 1611222 TI - Lack of effect of ovariectomy on divalent cation regulation of skeletal adenylate cyclase. AB - Both estrogen and androgen have been reported to attenuate cyclic AMP responses to parathyroid hormone stimulation in cultured bone cells. The present study examines the effect of in vivo estrogen deficiency on skeletal adenylate cyclase (AC) activity. The AC activity was compared in bone membranes prepared from normal female guinea pigs and from age-matched guinea pigs 3 weeks after ovariectomy. Histomorphometric analysis of femoral specimens from the ovariectomized guinea pigs demonstrated significant decreases in percentage bone volume, the percentage eroded surfaces and osteoclast numbers, and increased osteoid thickness, compared with the normal controls. No differences were found in basal AC activity, the ability of bone AC to be stimulated by parathyroid hormone (bPTH(1-34)) or isoproterenol, or in the regulation of AC activity by calcium and magnesium. We conclude that bone AC is not a direct target for estrogen effects on bone cells and that the reported effects of sex steroids on cAMP levels in bone cells probably act via an indirect mechanism. PMID- 1611223 TI - The effects of menopause and estrogen replacement therapy on the renal handling of calcium. AB - Mineral metabolism was studied in 99 premenopausal and 80 postmenopausal women both before and after 9-14 months of treatment with 50 micrograms/day transdermal estradiol. In estrogen-repleted subjects (premenopausal women and postmenopausal women on estrogen replacement therapy) total serum calcium was significantly lower (0.065 mmol/l; p less than 0.001) than in those who were estrogen-depleted (untreated postmenopausal women). This difference was smaller but still significant for calculated ultrafiltrable calcium (UFCa: 0.02-0.03 mmol/l; p less than 0.001). However, ionized calcium (both calculated and measured) was not different in the two groups of women. This finding explains why estrogen repletion does not induce changes in the serum level of intact parathyroid hormone (PTH), despite lower total or ultrafiltrable serum calcium. In a parallel study we have shown that intravenous administration of aminobutane bisphosphonate, a powerful inhibitor of bone resorption, produces similar decreases in serum calcium which were associated with significant increases in intact PTH. Estrogen-depleted women had, on the one hand, significantly higher serum levels of bicarbonate, anion gap, complexed calcium, pH, phosphate and alkaline phosphatase, and higher rates of tubular reabsorption of phosphate and urinary excretion of calcium and hydroxyproline. On the other hand they had lower serum chloride levels and lower rates of tubular reabsorption of calcium. Altogether these findings might indicate that estrogen deficiency decreases renal sensitivity to PTH. This is responsible for the higher serum phosphate and bicarbonate levels, the resulting mild metabolic alkalosis leading to higher serum levels of complexed ultrafiltrable calcium and higher rates of urinary excretion of calcium, but unchanged serum levels of ionized calcium and PTH. PMID- 1611224 TI - Bone histomorphometry of the iliac crest, and spinal fracture prevalence in atrophic and hypertrophic osteoarthritis of the hip. AB - While some authors report high bone density in osteoarthritis (OA), surgical experience with total hip arthroplasty (THA) for primary OA suggests the existence of osteoporotic subsets of patients. To identify these we analysed 107 iliac crest bone biopsies, taken at THA, by routine histomorphometry for trabecular structural and bone turnover features, and examined radiographs of the spine for vertebral fractures. Patients were grouped by hip osteophyte size (none, atrophic; small, hypotrophic; moderate, supertrophic; large, hypertrophic OA), and by major architectural disorganization of the hip (hip joint destruction, protrusio). We found hip joint destruction to be 3 times more common in atrophic than in supertrophic and hypertrophic OA (p less than 0.05). Overall, the OA patients had lower bone volume (p less than 0.05) and thinner trabeculae (p less than 0.05) than controls. Worst affected were patients with hip joint destruction and with protrusio: they also had fewer and more widely spaced trabeculae than controls (p less than 0.05). The spinal fracture prevalence was highest in patients with hip joint destruction (higher than in the general population), intermediate in those with protrusio or atrophic OA, and lowest in patients with supertrophic or hypertrophic OA. We conclude that OA hip patients with joint destruction or protrusio have a high prevalence of generalized osteoporosis, and that the larger the hip osteophytes, the lower is the prevalence of generalized osteoporosis. Our findings suggest that the generalized bone status may influence the outcome of OA of the hip. PMID- 1611225 TI - Targeted estrogen/progesterone replacement therapy for osteoporosis: calculation of health care cost savings. AB - Osteoporosis is a crippling affliction in which bone mass decreases, making it more susceptible to fracture. In postmenopausal women it presents most often as a hip, spinal, or forearm fracture. Adult women face a 15% lifetime risk of a hip fracture, and the annual costs of hip fractures alone are estimated at $7.3 billion in the United States. Since the 1970s, estrogen/progestogen therapy has been recognized as an effective intervention that reduces the risk of fractures. Recently, the development of methods for accurately determining bone mass and thus helping to predict bone fracture risk has made this intervention attractive for use in a targeted population. This report analyzes the health care costs and calculates the cost savings of coupling bone mineral density screening at the time of menopause with long-term estrogen/progestogen therapy for those most at risk for developing fractures. The model assumes that a cohort of 100,000 American white women, aged 50, are screened for bone mineral density and that 90% of the high-risk group (density less than 0.85 g/cm3) and 70% of the mid-risk group (density between 0.85 and 1.00 g/cm3) elect to take hormone replacement therapy for 15 years. Based on calculations of the costs of screening and hormone replacement therapy, and the savings in cost of treatment and lost productivity from reduced fractures, it is estimated that the present value of savings in cost of illness for this cohort over a 40-year period is $5.1 million.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611226 TI - Earlier wrist fracture: a confounding factor in distal forearm bone screening. AB - Thirty-six women aged 60, 70 or 80 years who had fractured one of their distal radii (Colles' fracture) 0 to 35 (median 10) years earlier were examined in this population-based study. Single photon measurements (SPA) were performed on both arms 1 cm and 6 cm proximal to the styloid process of the ulna. All women were questioned about earlier wrist fractures and which, if any, side had been affected. Information about the type and site of the fracture was also gathered from the hospital records. The bone mineral content (BMC) was found to be increased by almost 20% in the once-fractured radius at the distal measuring site (1 cm) when compared with the unaffected side. This difference did not seem to diminish with time. At the proximal measuring site there was no difference between the once-fractured and the non-fractured side. There was a progressive loss of bone mineral in the once-fractured arm during the first years after the fracture however. This appeared to be reversed after about 10 years to a relative gain, even though the correlation was weak. Six of the 36 women could not remember which side had been fractured and five could not remember having had such a fracture at all. Determination of osteoporosis by measuring forearm BMC with single photon densitometry is therefore of limited value in some women of the oldest age groups. PMID- 1611228 TI - Work in progress: a cross-correlation study on four DXA instruments designed to culminate in inter-manufacturer standardization. PMID- 1611227 TI - Potential value of urinary oestrogen assays in the identification of fast bone losers after the menopause. AB - We determined the rate of change of bone mineral content (BMC) in the distal forearm of 89 healthy postmenopausal women by single-photon absorptiometry. The BMC measurements were taken at 6- or 12-monthly intervals for up to 4 years. Urinary oestrogen excretion and anthropometry were assessed at the time of the first BMC measurement. Urinary oestradiol glucuronide (E2G) excretion was related to the rate of change of 'proximal' BMC in women 1-7 years past the menopause (r = 0.52, p less than 0.01). Body mass index was less highly correlated with the rate of change of BMC in these women (r = 0.41, p less than 0.05). We conclude that urinary E2G excretion could contribute to a screening procedure for the assessment in women soon after the menopause of the risk of osteoporotic fracture in later life. PMID- 1611229 TI - Bronchodilator properties of an inhaled leukotriene D4 antagonist (verlukast--MK 0679) in asthmatic patients. AB - The safety, tolerability and bronchodilator properties of inhaled verlukast (MK 0679), a new potent and selective LTD4-receptor antagonist, were studied in 12 asthmatic subjects with more than 15% increase in FEV1 after salbutamol inhalation. On three separate study days the patients inhaled placebo, verlukast 2 mg and verlukast 8 mg from a metered dose inhaler according to a randomized, double-blind, cross-over allocation schedule. Pulmonary function and tolerability were assessed regularly and after 8 h a second dose of test drug was inhaled. Thirty minutes later a beta 2-agonist dose-response curve was performed by inhaling salbutamol in cumulative doses of 200, 400 and 800 micrograms. Verlukast (8 mg) caused significant improvement in mean FEV1 from 1.5 through 8 h after inhalation as compared to placebo (P less than 0.05). The maximum change in FEV1 occurred at 2 h after inhalation with mean percent increases above baseline of 3.5, 7.7, and 9.2% after placebo, verlukast 2 mg and 8 mg, respectively. The bronchodilator response to inhaled salbutamol was significantly larger after verlukast 8 mg than after placebo pretreatment (P less than 0.05), whereas verlukast 2 mg afforded no additive bronchodilator effect. We conclude that inhalation of the LTD4-antagonist verlukast induces modest but significant bronchodilatation and may be beneficial in the treatment of asthma. PMID- 1611230 TI - Effect of inhaled terbutaline sulphate in relation to its deposition in the lungs. AB - We studied the effects of inhaled terbutaline on FEV1 and gas exchange, and the pattern of deposition within the lungs. To document this and to estimate the dose of terbutaline administered to the lungs, [99mTc]DTPA was added to nebulised terbutaline solution. The aerosol was deposited preferentially in large or small airways by using aerosols with different particle mass median diameters (1.5 and 4.8 microns) and different inhalation flow rates (0.25 and 1.0 l/s). The patients inhaled placebo and then three increasing doses of terbutaline (0.006, 0.02 and 0.08 mg to the lungs). Finally, 2 mg terbutaline was inhaled from a metered dose inhaler via a spacer. After each inhalation FEV1, PaO2 and PaCO2 was measured. The inhalation of small particles at a low flow resulted in a fairly uniform lung deposition, while larger particles at a higher flow resulted in heavy central deposition. Penetration index for small and large particles were 1.3 +/- 0.2 and 0.8 +/- 0.3 (P less than 0.001), respectively. In both groups FEV1 increased similarly with each dose, and at 0.02 and 0.08 mg the increase was significant (P less than 0.01). After eight metered doses of terbutaline sulphate (0.25 mg per dose) inhaled via a spacer, there was a further increase in FEV1 (P less than 0.001). Gas exchange did not differ between the two groups but if they were combined the DA-aO2 was significantly lower after metered doses than control (P less than 0.05). Thus, it appears that the site of deposition is not important for the bronchodilator effect of terbutaline, and gas exchange tended to improve with both modes of administration. PMID- 1611231 TI - A comparison of the speeds of action of salmeterol and salbutamol in reversing methacholine-induced bronchoconstriction. AB - We compared the speed of action of the long acting beta-agonist salmeterol with that of salbutamol in order to assess whether reported in vitro differences are likely to have clinical significance. We used methacholine tests to produce a standardized level of bronchoconstriction and then observed the rate of recovery of FEV1 towards baseline after the administration by metered dose inhaler of salmeterol 50 micrograms or salbutamol 200 micrograms--doses which are considered to have similar bronchodilator potency. Twenty asthmatic subjects participated, and a double-blind, randomized, cross-over study design was followed. Salmeterol showed a significantly slower speed of action with median recovery to 90% and 95% of the baseline FEV1 (pre-methacholine) occurring after 9.6 and 19.4 min, respectively, compared with 4.8 and 8.3 min, respectively, for salbutamol (P less than 0.01). These observations are consistent with in vitro findings and suggest that salmeterol is likely to be less satisfactory than salbutamol as a 'rescue medication' for the treatment of acute episodes of bronchoconstriction. PMID- 1611232 TI - Effect of mequitamium iodide (LG 30435) on airway microvascular leakage in the guinea-pig. AB - Intravenous administration of mequitamium iodide (LG 30435) prevented the increase of tracheobronchial vascular permeability induced either by antigen challenge or by exogenous histamine in the guinea-pig, while it was ineffective against PAF, serotonin or capsaicin. These findings indicate that mequitamium iodide selectively interferes with the effect of histamine on airway microvascular leakage, mediated by histamine H1 receptors, and is more potent than diphenhydramine, mequitazine or astemizole. Histamine receptor antagonism is likely to be major determinant of the antiallergic activity of the compound, although additional mechanisms may be involved. PMID- 1611233 TI - Peripheral site of action of levodropropizine in experimentally-induced cough: role of sensory neuropeptides. AB - The mechanism of action of levodropropizine has been investigated in different models of experimentally-induced cough in guinea-pigs. In particular it has been demonstrated that the antitussive drug has a peripheral site of action by injecting the drug intracerebroventricularly (i.c.v.). In these experiments levodropropizine (40 micrograms/50 microliters i.c.v.) did not prevent electrically-induced cough. On the other hand, codeine (5 micrograms/50 microliters i.c.v.) markedly prevented coughing. A difference in the potency ratio of levodropropizine and codeine has been demonstrated in capsaicin-induced cough; after oral administration, codeine was about two to three times more potent than levodropropizine. However, after aerosol administration the two compounds were equipotent. These data might suggest a peripheral site of action for levodropropizine which is related to sensory neuropeptides. Further support for the role of sensory neuropeptides in the mechanism of action of levodropropizine comes from the results obtained in capsaicin-desensitized animals. In this experimental model levodropropizine failed to prevent the vagally elicited cough in neuropeptide-depleted animals, whereas codeine did not differentiate between control and capsaicin-treated animals. In conclusion, our results support the suggestion that levodropropizine has a peripheral site of action. In addition, the interference with the sensory neuropeptide system may explain, at least in part, its activity in experimentally-induced cough. PMID- 1611234 TI - Modulation of cholinergic responses by N omega-nitro-L-arginine in rabbit intrapulmonary arteries. PMID- 1611235 TI - Early efficacy data with a newer generation of LTD4 antagonists in antiasthma trials: early promise for a single mediator antagonist. PMID- 1611236 TI - Mucus secretion and inflammation. PMID- 1611237 TI - Abamectin in the ambient air, on surfaces, and in food of dining facilities treated for cockroaches. PMID- 1611239 TI - Organochlorine pollutants in water, soils, and earthworms in the Guadalquivir River, Spain. PMID- 1611238 TI - Pollution due to volatile halocarbon compounds in biota. PMID- 1611240 TI - Organochlorine pesticide residues in estuarine fish from the Athi River, Kenya. PMID- 1611241 TI - Organochlorine pesticide residues in fish from Lake Naivasha and Tana River, Kenya. PMID- 1611242 TI - Organophosphorus pesticide residues in cow's milk: levels of cis-mevinfos, methyl parathion, and paraoxon. PMID- 1611244 TI - Toxicity reduction associated with bioremediation of gasoline-contaminated groundwaters. PMID- 1611243 TI - Chlorinated pesticide residue occurrence and distribution in mosquito control impoundments along the Florida Indian River Lagoon. PMID- 1611245 TI - ATP and adenylate energy charge determinations on core samples from an av-fuel spill site at the Traverse City, Michigan airport. PMID- 1611246 TI - Blood and tissue parameters in wild mallards redosed with lead shot. PMID- 1611247 TI - Bioassay for deoxynivalenol based on the interaction of T-2 toxin with trichothecene mycotoxins. PMID- 1611248 TI - Lethal and sublethal effects of Bacillus thuringiensis var. kurstaki on aquatic insects in laboratory bioassays and outdoor stream channels. PMID- 1611249 TI - Ames and sister chromatid exchange tests of organic extracts from drinking water. PMID- 1611250 TI - Acute toxicity of toluene, hexane, xylene, and benzene to the rotifers Brachionus calyciflorus and Brachionus plicatilis. PMID- 1611251 TI - Effect of mercury and cadmium on the growth of Anacystis nidulans. PMID- 1611252 TI - Variation in toxicity of malathion to air and water-breathing teleosts. PMID- 1611253 TI - Malformation of the fathead minnow (Pimephales promelas) in an ecosystem with elevated selenium concentrations. PMID- 1611254 TI - Effects of swimming pool sanitizing chemicals on turf grass. PMID- 1611255 TI - Effect of food flavor cinnamaldehyde on liver microsomal cytochrome P-450 in rats. PMID- 1611256 TI - Effect of tricresyl phosphate on humoral and cell-mediated immune responses in albino rats. PMID- 1611258 TI - [Role of cholestanol in the pathogenesis of cholesterol cholelithiasis]. AB - The proportion of cholestanol/cholesterol in hepatic and cystic bile was evaluated using capillary gas-chromatography in subjects with disturbances in the biliary system (biliary dyskinesia, chronic acalculous cholecystitis, chronic calculous cholecystitis). The proportion was also measured in bile "paste" and cholesterol choleliths. With progression of cholesterol cholelithiasis, the proportion cholestanol/cholesterol increases, reaching its maximum in the stone the center of which accumulates crystals of cholestanol-cholesterol dihydrate. An original conception is proposed on pathogenesis of cholesterol cholelithiasis in man. It considers cholestanol as factor-reason underlying various pathological processes running in cholesterol cholelithiasis. Cholestanol is suggested to mark cholesterol cholelithiasis. PMID- 1611257 TI - Effects of methylmercury on primary cultured rat hepatocytes: cell injury and inhibition of growth factor stimulated DNA synthesis. PMID- 1611260 TI - [Differential diagnosis of epileptic seizures and syncopal condition in atrioventricular block]. PMID- 1611259 TI - [Functional activity of leukocytes and enzyme indicators in acute intestinal infections]. AB - To assess functional activity of leukocytes, lipid peroxidation and enzymes indicating the severity of organ lesion in food poisoning and acute dysentery, the investigators employed the techniques of luminol- and biacridine-activated chemiluminescence of pure granulocyte population and whole blood, plasma chemiluminescence, assays of AAT, AsAT, AP, LDG. A relationship was established between chemiluminescence of leukocytes and whole blood, between leukocytic functional activity and the disease duration and severity. Indomethacin treatment of the patients reduced intoxication, did not affect leukocytic function, diminished plasma chemiluminescence. Functional activity of leukocytes and the enzymes levels were prognostically significant. Low response of leukocytes to the stimulus, i.e. a small rise of functional activity, served an unfavourable prognostic sign. A role of active oxygen forms produced by leukocytes is suggested in pathogenesis of alimentary toxo-infection. PMID- 1611261 TI - [Results of x-ray examination after selective proximal vagotomy with gastric drainage operation in duodenal ulcer]. PMID- 1611262 TI - [Cerebral infarction in hypertensive circulatory encephalopathy]. PMID- 1611263 TI - [Auricular diagnosis of cochleovestibular disorders]. PMID- 1611264 TI - [Nitroglycerin and artificial ventilation of the lungs in acute respiratory insufficiency]. PMID- 1611265 TI - [Thallium poisoning]. PMID- 1611266 TI - [Psychosomatic correlations in patients with neurocirculatory dystonia and effectiveness of their treatment with psychotropic drugs]. PMID- 1611267 TI - [Dynamics of hemostasis indicators during surgery in the aorto-ilio-femoral area under epidural anesthesia]. PMID- 1611268 TI - [Proteinase-inhibitors and renin in the pathogenesis of vascular insufficiency in acute pneumonia]. AB - The system proteinases-inhibitors and renin were studied in 105 acute pneumonia (AP) patients, the blood of whom was examined for concentrations of elastase, acid proteases (AP), alpha 1-inhibitor of proteases (alpha 1-IP), alpha 2 macroglobulin (alpha 2-MG) and active or inactive, total renin (TR). A separate group included 18 AP cases complicated by infective toxic shock (ITS). An imbalance was proved in the system proteinases-inhibitors with dominance of the inhibitory potential. In a "cold" variant of ITS proteolytic blood activity rose while the inhibitory capacity fell. Moderate and severe AP forms were associated with lowered blood levels of active R and elevated of inactive R, TR. In arterial hypotonia and ITS these changes were most demonstrable. Elastase, alpha 1-IP, alpha 2-MG and active R, inactive R, TR exhibited close correlation. The discussion covered mechanisms of hemodynamic disturbances in AP with consideration of depressed renin-angiotensin system and imbalance of proteinases and their inhibitors. PMID- 1611269 TI - [Effects of corinfar, nitrosorbide and apressin on external respiration and blood flow in chronic obstructive bronchitis]. PMID- 1611270 TI - [Surgical treatment of lung cancer complicated by pleural empyema]. PMID- 1611271 TI - [Retrosternal administration of antibiotics as a method of choice in regional lymphotropic therapy]. PMID- 1611272 TI - [Extracorporeal UV-irradiation of blood in medicine]. PMID- 1611273 TI - [Effects of splenic inductothermia on the state of the liver in patients with chronic hepatitis and diabetes mellitus]. PMID- 1611274 TI - [Criteria of temporary and continuous work incapacity in peptic ulcer]. PMID- 1611275 TI - [Hereditary predisposition to kidney diseases and its effect on the development of nephropathies in children and adults]. PMID- 1611276 TI - [Esophageal candidiasis in patients with hemoblastosis]. PMID- 1611277 TI - [Immunoglobulins in the mucous membrane of the stomach and duodenum in patients with peptic ulcer]. AB - Immunofluorescence was used to detect incidence of immunoglobulins M, G, A and secretory immunoglobulin A in gastric and duodenal mucosa of 72 patients with peptic ulcer. In the aggravated disease, duodenal mucosa contains IgM and secretory IgA more frequently than gastric one which has in more cases IgG and IgA. In ulcer remission, immunoglobulins of all classes are less frequent finding in duodenal mucosa, IgM and secretory IgA occurring more often in gastric mucosa. In recurrent disease, the occurrence of immunoglobulins in gastric mucosa decreases, in duodenal mucosa this is true only for IgA and secretory IgA. Ulcer patients with the disease duration more than 10 years demonstrate immunoglobulins in gastric mucosa less frequently, most rare of them being IgM and secretory IgA (p less than 0.05). The above changes in local immunity suggest pathogenetic involvement of immune mechanisms and can precondition clinical features of ulcer. PMID- 1611278 TI - [State of the kallikrein-kinin system in patients with chronic inflammatory diseases of the liver]. PMID- 1611279 TI - Intrinsic resistance to herpes simplex virus type 1 infection in liver Kupffer cells and peritoneal macrophages from normal and immunomodulator-treated mice. AB - In contrast with other macrophage (MO) populations, there is little information on the antiviral resistance in vitro of isolated liver MO (Kupffer cells, KC). We have demonstrated that the KC exhibits marked intrinsic resistance to infection in vitro with herpes simplex virus type 1 (HSV-1). Liver and peritoneal MO (PMO) were harvested from untreated mice (naive), from mice treated with drug vehicle, or from mice treated with either a synthetic nonspecific immunomodulator, maleic anhydride divinyl ether copolymer (MVE-2), or with MO colony-stimulating factor-1 (CSF-1). The studies revealed that resident KC, isolated by two different methods, are equally as nonpermissive for infection with HSV-1 as are resident PMO. When infected with HSV-1, resident KC showed no cytopathic effect, and no infectious virus was produced. Intravenous (i.v.) treatment of mice with MVE-2 (50 mg/kg 3 days before cell harvest) increased the number of KC recovered. However, neither i.v. treatment with MVE-2 nor CSF-1 (20,000 U daily for 4 days) had any pronounced effect on the permissiveness of KC or PMO to infection with HSV-1. These data support a role for KC in host antiviral resistance, and indicate that KC intrinsic antiviral resistance is maintained during immunotherapy with MVE-2 or CSF-1. PMID- 1611280 TI - WEHI-164 clone 2F: in vitro antitumor effects of tumor necrosis factor and gamma interferon. AB - Based on their enhanced susceptibility to tumor necrosis factor (TNF), sublines of the BALB/c fibrosarcoma WEHI-164 are more and more frequently being used to measure levels of TNF in cell-free supernatants. In studies aimed at characterizing the cytostatic and cytolytic effects of TNF and gamma-interferon (IFN-gamma) on a highly TNF-sensitive subline of WEHI-164, we show that: (1) the MTT assay which measures viable cell numbers (i.e. both cytostasis and cytolysis) at appropriate target cell numbers is sensitive to less than 0.1 pg/ml of recombinant murine TNF (rmTNF) without the need to add protein synthesis inhibitors such as actinomycin D; (2) using irradiated cells, the MTT assay is significantly more sensitive and measures cell lysis but not stasis; (3) clone 2F is sensitive to the cytostatic, but not cytolytic effects of recombinant murine IFN-gamma; (4) although lysis of 2F by rmTNF requires more than 5 h, a short exposure (30-60 min) to rmTNF is sufficient to trigger the lytic process, and (5) lysis of 2F is not cell-cycle-dependent. The use of highly sensitive indicator cell lines such as 2F allow for the measurement of low levels of TNF present in culture supernatants and for studies into the mechanism of action of TNF. However, sensitivity to other agents such as IFN supports the need to confirm that the antitumor effects seen are due to TNF via neutralizing antibody. PMID- 1611281 TI - Nonspecific stimulation of host defense by Corynebacterium kutscheri. III. Enhanced cytokine induction by the active moiety of C. kutscheri. AB - The present study was carried out to ascertain whether the active component of Corynebacterium kutscheri (CK-M) could stimulate host cells of mice to produce several cytokines. CK-M stimulated thioglycollate-induced peritoneal macrophages to produce interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha) at concentrations of 1-100 ng/ml, and it also induced IL-2 and interferon-gamma (IFN gamma) as well as IL-6 production by splenocytes. Maximum production of each cytokine induced by CK-M was obtained at the following doses: IL-1 at 5 ng/ml, TNF-alpha at 50 ng/ml, IL-2 at 1 microgram/ml, IL-6 at 500 ng/ml and IFN-gamma at 750 ng/ml. In contrast, IL-4 was not produced to a significant extent by CK-M stimulated splenocytes. Furthermore, when mice were intravenously injected with 20 micrograms of CK-M, IL-2 and IFN-gamma production by splenocytes, upon stimulation with either formalin-killed C. kutscheri or mitogens, was significantly higher on day 10 of treatment than on day 2. Additionally, the cytotoxicity to L929 cells of this serum from CK-M-treated mice increased with time, and the activity in the serum of day 10 was not abrogated by the antibody to TNF-alpha. Data obtained here indicate that CK-M may preferentially stimulate type-1 helper T cells to produce IL-2 and IFN-gamma, and that the enhanced cytokine production could contribute to the nonspecific resistance induced by C. kutscheri. PMID- 1611282 TI - LAK-cell-mediated cytotoxicity against tumor cell targets used to monitor the stimulatory effect of interleukin-2: cytotoxicity, target recognition and phenotype of effector cells lysing the Daudi, T24 and K562 tumor cell lines. AB - The T24 transitional bladder carcinoma cell line, the Daudi Burkitt lymphoma cell line and the K562 erythroleukemia cell line have all been used as target cells in 51Cr release assays to measure the in vivo induced lymphokine-activated killer (LAK) cell cytotoxicity during interleukin-2 (IL-2) therapy of cancer patients. However, different relationships between the clinical response to IL-2 treatment and the LAK cytotoxicity have been reported using these three different target cells. The purpose of the present study was to evaluate whether the LAK cytotoxicities measured against these target cells represent similar effector-to target-cell interactions, so similar conclusions may be drawn of 51Cr release assay results in which the cell lines are used as target cells. The cytotoxicity of peripheral blood mononuclear cells (PBMC) and PBMC depleted of different natural killer and T cell subsets was measured against the three targets. LAK cell recognition of targets was evaluated by cold target inhibition experiments, and the development of LAK-cell-mediated lysis with time was evaluated in 51Cr release assays of varying duration. This study shows that LAK-mediated lysis of T24 and Daudi cells was closely related and LAK cytotoxicity measured in 51Cr release assays against these two target cells may be measurement of similar effector-to-target cell interactions. PMID- 1611283 TI - Evaluating education in intensive care. AB - In its promotional literature for the Higher Award, the English National Board include a logo promoting 'Quality Education for Quality Care'. The purpose of this paper is to examine how we can assess the impact of continuing education, specifically the English National Board (ENB) Course 100, on quality of care in an Intensive Care Unit (ICU). The paper provides an examination of the relationship between education and practice, methods of evaluating education and the impact that the course can make on clinical practice. PMID- 1611284 TI - Current theories and therapies relating to acute myocardial infarction and reperfusion injury. AB - Acute myocardial infarction (AMI) was previously treated with conservative strategies that allowed the process of ischaemia to proceed uninterrupted. The resultant myocardial necrosis and reduced ventricular function were accepted outcomes. The emergence of thrombolytic agents such as streptokinase and tissue plasminogen activator (tPA) revolutionised the management of coronary artery occlusion, yet the spectre of further myocardial necrosis and ventricular dysfunction remains. The concept of 'reperfusion injury', an acute process described as occurring after thrombolysis of a coronary artery occlusion and referring to an unexpected loss of ventricular function, has been extensively researched. Current research papers describing the mechanisms involved appear either to emphasise those processes that occur within the actual myocytes, or those events within the coronary vasculature. In most papers however, oxygen free radicals (OFRs) are accepted as mediators of cellular injury; despite the debate surrounding their primary source. Efforts to minimise the effects of primary ischaemia and subsequent 'reperfusion injury', appear to be focused upon restoring cardioprotection against the increased levels of these damaging molecules. Scavenging agents such as N-acetylcysteine (NAC) which can also assist in dilating coronary vessels as well as preventing further platelet aggregation, when combined with glyceryl trinitrate (GTN), are being closely scrutinised. Despite the advances made, the processes within the myocardium remain somewhat a mystery and the search continues for more effective strategies to ensure myocardial viability and long-term function. Critical care nurses need not only to be aware of the aim of these new strategies, but should also be conscious of their effect on the patients receiving them. PMID- 1611285 TI - Acute myocardial infarction patients' chest pain as monitored and evaluated by ambulance personnel. AB - A delicate duty for ambulance personnel is to care for patients who suffer from chest pain, caused by acute myocardial infarction (AMI-patient). In Sweden pain relieving drugs may be administered, such as: oxygen, entonox, or morphine according to the skill of the ambulance personnel. The aim of this study was to find out if AMI-patients' expressions of pain were monitored and evaluated, in which way the AMI-patients received pain-relief, and to which degree they were relieved of pain. Examinations of the records of the ambulance personnel's observations during transport of AMI-patients revealed that nine tenths of those who complained about chest pain received pain-relieving drugs. The results of the treatments varied, however, from a good rate of response to morphine to less responses to oxygen and entonox. In order to treat AMI-patients who are in need of pain-relief during their transit to hospital the ambulance personnel must possess thorough knowledge of both pain theory and communication theory. Furthermore, they need tools for assessment of pain and for administering adequate pain-relieving drugs in clinical practice. In the future it may be necessary to differentiate between ambulance personnel in routine service and those in emergency service according to their levels of education. PMID- 1611287 TI - Too much theory for practice? PMID- 1611286 TI - Reconstructing nursing: a coronary care perspective of the primary nurse philosophy. AB - The philosophy underpinning the system of primary nursing and how it relates to the reconstruction of nursing merits consideration. This includes examination of the relationship of primary nursing to the concept and practice of caring: the movement of nursing to humanitarianism from pragmatism and the relationship to a process rather than a traditional system of nursing. Arguments concerning these topics are presented here and discussed in relation to the experiences and practice of a group of nurses in a Coronary Care Unit (CCU) before and after the introduction of a system of nursing based on the primary care philosophy. PMID- 1611288 TI - Continuous monitoring of mixed venous saturation (SvO2): an adjunct to nursing assessment? AB - Technological advances in oximetry have enabled the development of a pulmonary artery catheter which allows the continuous monitoring of a patient's mixed venous oxygen saturation (SvO2), which is recognised as a valuable indication of cardiac output and the balance between oxygen supply and demand (delivery and consumption). This paper briefly explains the rationale for monitoring SvO2 and highlights possible areas where the data it provides could influence the assessment and implementation of nursing interventions undertaken within intensive care units, and enable those decisions to be made more safely. PMID- 1611289 TI - The clinical nurse specialist--a personal perspective. AB - The post of clinical nurse specialist (CNS) is relatively new in the United Kingdom, and research so far suggests that the intensive care unit is an appropriate area for the further development of the role (Thompson et al, 1986). The purpose of this paper is to examine the function of a clinical nurse specialist within an intensive care unit, and to discuss the various aspects that constitute the role, within the fields of clinical practice, education, research and management. Nursing practice is developing--the aim being truly individualised patient care. A clinical nurse specialist should be in an ideal position to innovate, lead and evaluate change. PMID- 1611290 TI - Perceived competence in cardiopulmonary resuscitation, knowledge and skills, amongst 50 qualified nurses. AB - 50 qualified nurses were surveyed regarding their perception of their competence in resuscitation and cardiology-related skills. This included the ability to place a patient on a cardiac monitor, the identification of 7 basic arrhythmias and the ability to offer correctly to the anaesthetist the equipment for airway intubation and central venous cannulation during the cardiac arrest situation. Generally, there was not a satisfactory level of knowledge, with only 10 nurses (20%) feeling competent in identifying all 7 basic arrhythmias. 33 nurses (66%) believed that they were competent in handling the anaesthetist the correct equipment for intubation, but only 22 nurses (44%) stated competence in offering the correct equipment for central venous cannulation. A review of the literature reveals that there is a considerable disparity between perceived competence and the actual ability to carry out the resuscitation skills. This survey once again reinforces the urgent need for regular assessment and updating of resuscitation skills, knowledge and practice amongst nurses, particularly those working in the ward areas. PMID- 1611291 TI - The changing role of coronary care nurses. AB - The purpose in this article is to give an overview of the role of a coronary care nurse. No attempt is made to give a detailed account of any particular aspect of care but rather to inspire coronary care nurses to think about their practice and what can be achieved. In the 1960s Coronary Care Units (CCUs) were shown to reduce mortality from fatal arrhythmias and nursing care was based around observation and emergency treatment. The focus of coronary care is now moving towards infarct size reduction and the prevention of infarction in patients with unstable angina. Nurses are adapting their role accordingly--the skill, knowledge and judgement required to recognise reversible ischaemic episodes in the early pre- or post-infarctional period is paramount. It is equally and vitally important that nurses are able to recognise and assess the psychological and rehabilitation needs of patients. These aspects of care can be met ideally by using a system based on primary nursing and focusing on the patients' individual needs. Nursing practice should be research-based, and under constant review with positive change encouraged. PMID- 1611292 TI - Aspects of neurosurgical assessment using the Glasgow Coma Scale. AB - The Glasgow Coma Scale (GCS) has become a cornerstone of the neurological/surgical assessment of patients used by both nursing and medical staff. Since its development in the 1970s it has been used in a variety of clinical situations to monitor changes in a number of key neurological functions, including level of consciousness, pupil reaction and limb movement. During this time, however, there have been suggestions that there are problems with some of the measurement principles underlying its use, which in part has stimulated the development of other neuro-assessment tools. Irrespective of measurement device, there is always the possibility of error or incorrect assessment. In the field of neurosurgery, as with other high dependency environments, a patient's condition can change rapidly. Additionally, there is the association of certain assessment responses with nursing and medical interventions. Thus, accuracy in all aspects of assessment and recording is paramount. Despite the growing body of literature surrounding the GCS, little is known about the pattern of errors made by nursing staff using the GCS to assess neurosurgical patients. This study compared the assessment findings of Registered General Nurses (RGNs), Enrolled Nurses and Student Nurses after viewing videotaped neuro-assessments of patients in a high dependency unit. The criterion for judging the accuracy of subject's assessments was established by a panel of experts. As expected, RGNs had the highest proportion of correct assessments and students the least. Subjects were identified as having difficulty in determining the relative amounts of weakness that a patient exhibited, and in correctly distinguishing between flexion and extension. PMID- 1611293 TI - [Repair of fractured metal-ceramic. Optec H.S.P. procedure]. PMID- 1611294 TI - Microcrystal deposition in cartilage and in osteoarthritis. PMID- 1611295 TI - Comparison of normal and rachitic rat matrix vesicles. AB - Accumulated information about MVs in PO4-deficient rachitic rats shows them to be normal in most aspects. Both normal and rachitic MVs show the same ultrastructural features and selective spatial distribution in the growth plate, and both contain a nearly identical array of major proteins. Rachitic and normal MVs show the same avidity to calcify in vivo and in vitro. A slightly greater specific activity of ALP in rachitic MVs may enhance their calcifiability. We conclude that rachitic rat MVs are essentially 'normal' and can be used as an adequate model to study the mechanism of biological calcification. PMID- 1611296 TI - Abnormal collagen and mineral formation in osteogenesis imperfecta. PMID- 1611297 TI - Bioprosthetic heart valve calcification: membrane-mediated events and alkaline phosphatase. PMID- 1611298 TI - In vivo regulation of matrix vesicle concentration and enzyme activity during primary bone formation. AB - In vivo regulation of matrix vesicles (MV) during primary bone formation was examined using tibial marrow ablation in rats as the experimental model. The effects of bone-bonding and nonbonding implants on the number of MV/micron 2 of matrix and the alkaline phosphatase (ALPase) and phospholipase A2 (PA2) activities of MV-enriched microsomes (MVEM) isolated from the healing bone were studied. MV concentration, ALPase, and PA2 were increased by bone-bonding implants by day 3 post-surgery; a similar effect was seen in the contralateral limb, but at a lower magnitude. Nonbonding implants had no effect at day 3 and decreased MV concentration and PA2 activity at later time points; the same behavior was observed in the contralateral limb. These results demonstrate that MVs are influenced in a differential manner by implant materials, both locally and systemically, and can be regulated during primary mineralization. PMID- 1611299 TI - Stimulation of matrix vesicle enzyme activity in osteoblast-like cells by 1,25(OH)2D3 and transforming growth factor beta (TGF beta). AB - After demonstrating the presence of matrix vesicles in three osteosarcoma cell lines, MG-63, ROS 17/2.8 and MC-3T3-E1, we sought to determine whether two major enzymes localized to matrix vesicles, alkaline phosphatase and phospholipase A2, could be regulated by 1,25(OH)2D3 and/or TGF beta. Intravesicular calcification is probably dependent on these two enzymes. Alkaline phosphatase is essential for hydrolysis of phosphate-containing substrates and phospholipase A2 hydrolyzes diacylphosphatides in a calcium-mediated manner at lipid-aqueous interfaces leading to changes in membrane fluidity and possibly breakdown of the matrix vesicle. The 1,25(OH)2D3 induced increase of alkaline phosphatase in bone cells is localized to the matrix vesicle. TGF beta also increased alkaline phosphatase activity in two of the cell lines, MG-63 and ROS 17/2.8 but to a greater degree than 1,25(OH)2D3. Matrix vesicle alkaline phosphatase activity exhibited a greater response than that in the plasma membrane. TGF beta increased phospholipase A2 activity in both matrix vesicles and plasma membranes, therefore, no targeting was observed with respect to this enzyme. When TGF beta was combined with 1,25(OH)2D3, 1,25(OH)2D3 had no effect on phospholipase A2 and did not interfere with TGF beta stimulation of phospholipase A2 activity. When 1,25(OH)2D3 and TGF beta were combined, a tremendous synergy was observed in alkaline phosphatase specific activity in both plasma membranes and matrix vesicles with targeting to matrix vesicles. Therefore, TGF beta not only plays an important role in matrix formation and differentiation, but works in conjunction with 1,25(OH)2D3 to greatly potentiate the effects seen with 1,25(OH)2D3 alone. PMID- 1611300 TI - Human osteosarcoma cells spontaneously release matrix-vesicle-like structures with the capacity to mineralize. AB - Nearly all models of skeleton, cartilage, and dentin mineralization evoke a specific role for matrix vesicles (MV) and alkaline phosphatase (ALP). Nevertheless, the mechanism underlying MV production, mineralization, and the pivotal role of ALP is largely unknown. Previous studies in this laboratory demonstrated that ALP in a human osteosarcoma cell line (SAOS-2) is of the tissue nonspecific ('bone') isoenzyme and lipid-anchored to the plasma membrane in ecto orientation [1], thus reminiscent of osteoblasts in vivo [2]. Herein, we show that these cells spontaneously release ALP-rich structures (MVs) with the capacity to mineralize. MVs from SAOS-2 cells are 100-200 nm in diameter with characteristic trilaminar membranes. ALP in these vesicles is hydrophobic and lipid-anchored in ecto-orientation in a manner similar to the ALP in the parent SAOS-2 cells. 5'-Nucleotidase, another plasma membrane enzyme, is also abundant in MVs; adenylate cyclase is relatively deficient. Analysis of plasma membrane and MV proteins by 2-D gel electrophoresis reveals many common constituents; nevertheless, MVs contain several unique (or greatly enriched) proteins indicating that SAOS-2 MVs originate from specialized regions of the plasma membrane and are released in the same orientation as the plasma membrane. MVs, unlike plasma membrane vesicles, can cause the formation of insoluble calcium and phosphate in a manner that i) requires ALP substrates; ii) is blocked by ALP inhibition or inactivation; and iii) is not dependent on intact MVs. SAOS-2 derived MVs contain at least 3 protein kinases and their substrates. ALP does not, however, have a major role in regulating the phosphorylation state of these phosphoproteins. PMID- 1611301 TI - Development of an in vitro mineralization model with growth plate chondrocytes that does not require beta-glycerophosphate. PMID- 1611302 TI - Induction of matrix vesicles in ossifying cartilage: comparison between deflazacort and fluorinated synthetic glucocorticoids. PMID- 1611303 TI - The effect of bone injury on extracellular matrix vesicle proliferation and mineral formation. AB - Removal of tibial bone marrow in rats is followed by primary bone formation, resorption and marrow restitution. The first week of healing is characterized by partially calcified trabeculae. After 2 weeks, a higher degree of calcification and partial resorption are observed. The third week is characterized by massive resorption of the trabeculae, which are replaced in the fourth week by new bone marrow tissue. This model was used to study primary calcification. Transmission electron micrographs of the young bone revealed osteoblasts, matrix vesicles and calcified fronts. The different vesicular types were defined as 'empty', 'amorphous', 'crystal', and 'rupture'. The vesicles were studied on days 3, 6, 8, 12, 14, 18, 21, 23 and 28 after injury. The mean diameters of most vesicles ranged between 100.3 and 121.9 nm, and their mean distance from the calcified front was less than 976.6 nm. Vesicular density, calculated as number per 10 m2, increased on the eighth day and decreased from the fourteenth day onwards. Highest diameter values were recorded on the sixth day, and decreased onward. Vesicular distance from the calcified front decreased continuously. Distribution of vesicle number, diameter, and distance in each class showed that numbers of empty and amorphous vesicles decreased and of crystal and rupture increased throughout the experiment. Distances from the calcified front and vesicular diameters varied as follows: 'rupture', 'crystal', amorphous', and 'empty', the 'rupture' type being the closest to the front and of the largest diameter. The results confirm the hypothesis that the cell is responsible for the secretion of electron lucent vesicles that accumulate Ca and Pi to form amorphous calcium phosphate complexes that convert to hydroxyapatite. Crystal growth is followed by membrane rupture. PMID- 1611304 TI - Constitutive enzymes of matrix vesicles. PMID- 1611305 TI - Matrix vesicles contain metalloproteinases that degrade proteoglycans. AB - This study explored whether extracellular matrix processing enzymes are present in matrix vesicles produced by rat costochondral resting zone and growth zone chondrocytes in culture. It was found that there was a differential distribution of enzyme activities related to the cartilage zone from which the cells were isolated. There was a 3-fold enrichment of total and active acid metalloproteinase in growth zone chondrocyte (GC) matrix vesicles whereas no enrichment in enzyme activity was observed in resting zone chondrocyte (RC) matrix vesicles. Total and active neutral metalloproteinase were similarly enriched 2-fold in GC matrix vesicles. TIMP, plasminogen activator and beta glucuronidase activities were highest in the plasma membranes of both cell types. No collagenase, lysozyme, or hyaluronidase activity was found. The data indicate that matrix vesicles are selectively enriched in enzymes that degrade proteoglycans. The highest concentrations of these enzymes are found in matrix vesicles produced by growth zone chondrocytes, suggesting that this may be a mechanism by which the more differentiated cell modulates the matrix for calcification. PMID- 1611306 TI - Lactate dehydrogenase isoenzymes in matrix vesicles (review). AB - Matrix vesicles (MV) isolated from mineralizing tissues contain high alkaline phosphatase (ALPase) activities associated with the membrane; this may be because MV originate from the plasma membrane of chondrocytes. Previous studies in our laboratory demonstrated that lactate dehydrogenase (LDH) isoenzymes, which appeared to be derived from chondrocytes cytosol, were located in MV of the epiphyseal growth plate of young-rabbit leg bones [1]. In the epiphyseal cartilage, alkaline phosphatase (ALPase) is enriched in the growth zone, whereas it is rarely detected in the resting zone, suggesting that MV containing ALPase are not present in the resting zone. In recent study, we divided the epiphyseal cartilages of young-rat rib bones into the growth zone and the resting zone, followed by the isolation of MV after collagenase digestion. MV containing ALPase and LDH were found in the growth zone, and surprisingly, vesicles containing LDH without ALPase were found in the resting zone [2]. The function of LDH-containing vesicles without ALPase is unknown at the present. However, these findings might accelerate the studies on cell-mediated calcification, because (1) LDH could be a marker enzyme of these vesicles, (2) LDH is found to be a specific cytosolic enzyme which is enfolded in these vesicles, suggesting that an unknown mechanism for the specific uptake of the cytosolic enzyme might be present. PMID- 1611307 TI - Development of a monoclonal antibody specific for human bone alkaline phosphatase. PMID- 1611308 TI - Presence and specific concentration of carbonic anhydrase II in matrix vesicles. AB - Matrix vesicles were isolated from the epiphyseal growth plates of normal weanling rats, and the presence of carbonic anhydrase II was demonstrated by Western blotting and ultrastructural immunolocalization using the immunogold technique. Total carbonic anhydrase activity was assayed and showed a statistically significant increase in matrix vesicles as compared to normal rat chondrocytes derived from the same growth plates. These results are the first to establish the presence of carbonic anhydrase in matrix vesicles. PMID- 1611309 TI - Identification of calbindin-D9k in matrix vesicles. PMID- 1611310 TI - Comments on the ultrastructural morphology of the calcification process: an attempt to reconcile matrix vesicles, collagen fibrils, and crystal ghosts. PMID- 1611311 TI - Type X collagen: covalent crosslinking to hypertrophic cartilage-collagen fibrils. PMID- 1611312 TI - Creatine kinase activity is required for mineral deposition and matrix synthesis in endochondral growth cartilage. AB - In earlier studies, we have drawn attention to the unique changes in energy metabolism that accompany the maturation of epiphyseal growth plate chondrocytes. The objective of this investigation was to examine the importance of the ATP generating enzyme creatine kinase (CK), in the development and mineralization of the growth plate. We inhibited CK function by administering beta guanidinopropionic acid (beta-GPA) to rats in vivo and to cultured chick chondrocytes in vitro. We found that this agent inhibited normal development of cartilage. Disorganization of chondrocytes in the proliferative and hypertrophic zones, poor vascular invasion, and retention of calcified cartilage occurred in the long bones of beta-GPA-fed rats. beta-GPA caused a change in the electrophoretic mobility of type II and type X collagens. Inhibition of apatite formation in the bones of shell-less chick embryos was accompanied by a CK isoenzyme shift from a bone-specific phenotype to a CK isozyme profile similar to that of cartilage. The results of these studies indicate that CK activity is required for normal development of the growth plate and that interference with creatine phosphate metabolism results in profound changes in the synthesis of cartilage and the maturational activities of chondrocytes. PMID- 1611313 TI - Extracellular vesicles of calcifying turkey leg tendon characterized by immunocytochemistry and high voltage electron microscopic tomography and 3-D graphic image reconstruction. AB - To gain insight into the structure and possible function of extracellular vesicles in certain calcifying vertebrate tissues, normally mineralizing leg tendons from the domestic turkey, Meleagris gallopavo, have been studied in two separate investigations, one concerning the electron microscopic immunolocalization of the 66 kDa phosphoprotein, osteopontin, and the other detailing the organization and distribution of mineral crystals associated with the vesicles as determined by high voltage microscopic tomography and 3-D graphic image reconstruction. Immunolabeling shows that osteopontin is related to extracellular vesicles of the tendon in the sense that its initial presence appears coincident with the development of mineral associated with the vesicle loci. By high voltage electron microscopy and 3-D imaging techniques, mineral crystals are found to consist of small irregularly shaped particles somewhat randomly oriented throughout individual vesicles sites. Their appearance is different from that found for the mineral observed within calcifying tendon collagen, and their 3-D disposition is not regularly ordered. Possible spatial and temporal relationships of vesicles, osteopontin, mineral, and collagen are being examined further by these approaches. PMID- 1611314 TI - Ascorbic acid induction of chondrocyte maturation. PMID- 1611315 TI - Evidence for specific interaction between matrix vesicle proteins and the connective tissue matrix. PMID- 1611316 TI - Structural and chemical analyses of mineralization using the turkey leg tendon as a model tissue. PMID- 1611317 TI - Studies of matrix vesicle-induced mineralization in a gelatin gel. AB - Matrix vesicles isolated from fourth-passage cultures of chondrocytes were tested for their ability to induce hydroxyapatite formation in a gelatin gel in order to gain insight into the function of matrix vesicles in in situ mineralization. These matrix vesicles did not appear to be hydroxyapatite nucleators per se since the extent of mineral accumulation in the gel diffusion system was not altered by the presence of matrix vesicles alone, and in the vesicle containing gels, mineral crystals were formed whether associated with vesicles or not. In gels with these matrix vesicles and beta-glycerophosphate, despite the presence of alkaline phosphatase activity, there was no increase in mineral deposition. This suggested that in the gel system these culture-derived vesicles did not increase local phosphate concentrations. However, when known inhibitors of mineral crystal formation and growth (proteoglycan aggregates [4 mg/ml], or ATP [1 mM], or both proteoglycan and ATP) were included in the gel, more mineral was deposited in gels with the vesicles than in comparable gels without vesicles, indicating that enzymes within these vesicles were functioning to remove the inhibition. These data support the suggestion that one function of the extracellular matrix vesicles is to transport enzymes for matrix modification. PMID- 1611318 TI - Cell maturation-specific autocrine/paracrine regulation of matrix vesicles. AB - Matrix vesicles are extracellular organelles produced with distinctive phospholipid composition and enzyme activity. They are produced by cells which typically calcify their extracellular matrix and their characteristics are cell maturation dependent. Regulation of matrix vesicle structure and function occurs at the genomic and non-genomic levels. By following alkaline phosphatase gene transcription, protein concentration, and enzyme specific activity, we have shown that steroid hormones and growth factors exhibit a regulatory influence over gene transcription, protein synthesis, and matrix vesicle activity. Matrix vesicles respond to peptide hormones, other matrix proteins, like alpha 2-HS-glycoprotein, and autocoid mediators as well. Matrix vesicle metabolism can be directly affected by vitamin D metabolites, even in the absence of cells. The results indicate that 1,25-(OH)2D3(1,25D) or 24,25-(OH)2D3(24,25D) produced by the cells in culture can modulate matrix vesicle activity, and suggest that calcifying cells can modulate events in the matrix via autocrine/paracrine stimulation or inhibition of the matrix vesicles. 1,25D and 24,25D regulate matrix vesicle phospholipase A2 activity, fatty acid turnover, arachidonic acid release, PGE2 production and membrane fluidity, which act on the matrix vesicle to alter enzyme activity. Since vitamin D metabolite production is sensitive to both hormones and growth factors, there is potential for fine tuning matrix vesicle behavior. PMID- 1611319 TI - Mixed phospholipid liposome calcification. AB - Synthetic lipid vesicle (liposome) suspensions have been used to experimentally model many of the calcium phosphate precipitation steps observed in matrix vesicle (MV) calcification. In particular, precipitate development in liposomes can be made to preferentially follow the progression seen in MV, i.e. to occur initially in intraliposomal spaces and then to expand into the surrounding suspending medium. This paper reviews results from studies by us which show that certain phospholipid (PL) constituents of the liposomal membrane can modulate this progression. Of greatest relevance to MV calcification is the observation that phosphatidylserine and sphingomyelin, two lipids selectively enriched in MV, slow the expansion of the precipitation from inside to outside the liposome. PMID- 1611320 TI - The role of alkaline phosphatase in cartilage mineralization. PMID- 1611321 TI - Further studies on ATP-mediated Ca deposition by isolated matrix vesicles. PMID- 1611322 TI - Selected bibliography. PMID- 1611323 TI - Travelling hopefully, returning ill. PMID- 1611324 TI - Altitude induced illness. PMID- 1611325 TI - Making air crashes more survivable. PMID- 1611326 TI - Smoke hoods in aeroplanes. PMID- 1611327 TI - To wake in fright. PMID- 1611328 TI - Adverse drug reactions and secrecy. PMID- 1611329 TI - Treatment of familial hypercholesterolaemia. United Kingdom lipid clinics study of pravastatin and cholestyramine. AB - OBJECTIVE: To compare the efficacy and safety of cholestyramine, an anion exchange resin, and pravastatin, a new hydrophilic specific inhibitor of 3 hydroxy-3-methylglutaryl coenzyme A reductase, in the treatment of heterozygous familial hypercholesterolaemia. DESIGN: Double blind, double dummy, placebo controlled study with three parallel groups. SETTING: Six specialist lipid clinics in the United Kingdom. PATIENTS: 128 patients aged 18-70 with heterozygous familial hypercholesterolaemia diagnosed on strict biochemical and clinical findings. MAIN OUTCOME MEASURES: Total plasma cholesterol, triglyceride, and lipoprotein subfractions and biochemical and haematological safety parameters. RESULTS: Pravastatin (40 mg/day) led to a 25% reduction in total plasma cholesterol concentration and a reduction in low density lipoprotein cholesterol concentration of 30%. Cholestyramine (24 g/day) led to similar reductions in concentrations of total cholesterol (23%) and low density lipoprotein cholesterol (31%). No consistent changes occurred in high density lipoprotein cholesterol values with either compound. Plasma triglyceride concentrations showed a small rise (18%) on resin therapy. No serious adverse drug reactions occurred during the study. CONCLUSIONS: Pravastatin seems to be a highly effective, well tolerated drug for severe hypercholesterolaemia. Patients chosen for this study were recruited on the basis that they could tolerate a full dose of cholestyramine, and in this situation cholestyramine was also highly effective in lowering plasma low density lipoprotein cholesterol concentrations. PMID- 1611330 TI - Potential for cadaveric organ retrieval in New South Wales. AB - OBJECTIVES: To measure the potential for cadaver organ retrieval in New South Wales and to determine the reasons for potential donors failing to become actual donors. DESIGN: Prospective audit of all patients dying in five hospitals in New South Wales between 1 December 1989 and 30 November 1990; quality assurance of the data by independent medical specialist and if disagreement by study committee. PATIENTS: 2879 patients (100% of all deaths) yielding 364 patients with coma and 181 potential donors. OUTCOME MEASURES: Realistic medically suitable potential donor rate, missed potential donor rate, rate of potential donors with permission refused, donor rate, reasons for realistic medically suitable potential donors failing to become actual donors. RESULTS: 2879 deaths yielded 73 medically suitable potential donors, resulting in 19 actual donors, 30 missed potential donors, 19 potential donors with permission refused, and five in whom adequate resuscitation failed. The most common reason for a potential donor failing to become an actual donor was a decision by the senior medical practitioner to withdraw or not to institute ventilatory or haemodynamic support (26/73). The second major obstacle was refusal of permission by the next of kin (17/73). Assuming that the potential donor rate was that implied by the observed donor rate (13/million population/year) the projected missed potential donor rate was 9/million population/year (95% confidence interval 4 to 15) and the projected rate of potential donors with permission refused was 13/million population/year (95% confidence interval 5 to 22). Assuming that the rate of potential donors in the study hospitals was the same as in the other New South Wales hospitals, the projected donor rate for New South Wales was 18/million population/year (10 to 26); the projected missed potential donor rate was 15/million population/year (7 to 23); and the projected rate of potential donors with permission refused was 18/million population/year (10 to 27). CONCLUSIONS: The donor rate could be increased 70%-80% by overcoming the reluctance of medical practitioners to resuscitate missed potential donors and increased further by gaining permission for organ retrieval from the next of kin. PMID- 1611331 TI - Risk of second brain tumour after conservative surgery and radiotherapy for pituitary adenoma. AB - OBJECTIVE: To assess the risk of second brain tumour in patients with pituitary adenoma treated with conservative surgery and external beam radiotherapy. DESIGN: Long term follow up of a cohort of patients with pituitary adenoma and comparison of tumour occurrence with population incidence rates. SETTING: The Royal Marsden Hospital. SUBJECTS: 334 patients with pituitary adenoma treated with conservative surgery and radiotherapy (median dose 45 Gy) and followed up for 3760 person years. MAIN OUTCOME MEASURES: Second intracranial tumour and systemic malignancy. RESULTS: Five patients developed a second brain tumour: two had astrocytoma, two meningioma, and one meningeal sarcoma. The cumulative risk of developing a second brain tumour over the first 10 years after treatment was 1.3% (95% confidence interval 0.4% to 3.9%) and over 20 years 1.9% (0.7% to 5.0%). The relative risk of a second brain tumour compared with the incidence in the normal population was 9.38 (3.05 to 21.89). There was no excess risk of any other type of second primary malignancy. CONCLUSIONS: There is an increased risk of second intracranial tumour in patients with pituitary adenoma treated with surgery and radiotherapy. Although radiation is likely to be the most important factor contributing to the excess risk, further study is required in a cohort of similar patients not receiving radiation. PMID- 1611332 TI - Survey of 3765 cardiopulmonary resuscitations in British hospitals (the BRESUS Study): methods and overall results. AB - OBJECTIVE: To determine the circumstances, incidence, and outcome of cardiopulmonary resuscitation in British hospitals. DESIGN: Hospitals registered all cardiopulmonary resuscitation attempts for 12 months or longer and followed survival to one year. SETTING: 12 metropolitan, provincial, teaching, and non teaching hospitals across Britain. SUBJECTS: 3765 patients in whom a resuscitation attempt was performed, including 927 in whom the onset of arrest was outside the hospital. MAIN OUTCOME MEASURE: Survival after initial resuscitation, at 24 hours, at discharge from hospital, and at one year, calculated by the life table method. RESULTS: There were 417 known survivors at one year, with 214 lost to follow up. By life table analysis for every eight attempted resuscitations there were three immediate survivors, two at 24 hours, 1.5 leaving hospital alive, and one alive at one year. Survival at one year was 12.5% including out of hospital cases and 15.0% not including these cases. Each hospital year averaged 30 survivors at one year: three who had an arrest outside hospital, seven who had one in the accident and emergency department, seven in the cardiac care unit, 10 in the general wards, and three in other, non-ward areas. Within the hospitals survival rates were best in those who had an arrest in the accident and emergency department, the cardiac care unit, or other specialised units. Outcome varied 12-fold in subgroups defined by age, type of arrest, and place of arrest. CONCLUSION: 71% of the mortality at one year in patients undergoing attempted resuscitation occurred during the initial arrest. Hospital resuscitation is life saving and cost effective and warrants appropriate attention, training, coordination, and equipment. PMID- 1611333 TI - Measuring the heights of very young children. PMID- 1611334 TI - "Thirst strike": hypernatraemia and acute prerenal failure in a prisoner who refused to drink. PMID- 1611335 TI - Targeting asthma care in general practice using a morbidity index. AB - OBJECTIVES: To evaluate a morbidity index as a postal surveillance tool in defining previously diagnosed asthmatic patients needing extra education or management; to determine the accuracy of a computerised asthma register in general practice. DESIGN: Postal questionnaire survey of asthmatic patients identified from a computer register. Questionnaire comprised three morbidity questions, two questions about current asthma status, and one about treatments. SETTING: Urban general practice of 8400 patients linked to academic unit. SUBJECTS: 853 asthmatic patients of all ages. MAIN OUTCOME MEASURES: Numbers of patients with low, medium, and high morbidity; associations of these groups with age, asthma status, and drugs taken. RESULTS: Two mailings yielded 621 replies (73%); 28 patients (5%) had moved away, leaving 593 for analysis. Attempts were subsequently made to contact 20% sample of non-respondents. 234 respondents (40%) were in the "low morbidity" group, 149 (25%) in the "medium morbidity" group, and 210 (35%) in the "high morbidity" category. 53% of patients perceiving themselves as currently asthmatic (193/362) were in the high morbidity group, but 7% (11/153) who said they were no longer asthmatic and 8% (6/78) who did not believe they had ever been asthmatic were also in that group. High morbidity was also found in 10% (18/185) of those on no treatment, 38% (59/154) of those on bronchodilators alone, and 54% (119/220) of those on inhaled corticosteroids. 25 patients (4%) were wrongly identified as asthmatic; when combined with returns marked "gone away" this gave a disease register accuracy of 91%. CONCLUSIONS: This exercise identified subgroups of previously diagnosed asthmatic patients with high morbidity in general practice who might benefit from extra education and management and revealed some misclassification on the asthma disease register. PMID- 1611336 TI - Managing change in general practice: introduction. PMID- 1611337 TI - Quality control: an application of the cusum. PMID- 1611338 TI - Management of early breast cancer. PMID- 1611339 TI - ABC of colorectal diseases. Non-specific inflammatory bowel disease. PMID- 1611340 TI - Gastric cancer. PMID- 1611341 TI - New study of suicides needed. PMID- 1611342 TI - Suicides in prison. PMID- 1611343 TI - Treating elderly patients with breast cancer. PMID- 1611344 TI - Treating elderly patients with breast cancer. PMID- 1611345 TI - Aggressiveness of breast cancers detected by screening. PMID- 1611346 TI - Nurse triage in accident and emergency departments. PMID- 1611347 TI - Nurse triage in accident and emergency departments. PMID- 1611348 TI - Nurse triage in accident and emergency departments. PMID- 1611349 TI - Nurse triage in accident and emergency departments. PMID- 1611350 TI - Nurse triage in accident and emergency departments. PMID- 1611351 TI - Nurse triage in accident and emergency departments. PMID- 1611352 TI - In search of the unknown primary. PMID- 1611353 TI - Oesophageal cancer in Britain. PMID- 1611355 TI - Childhood mortality after high dose vitamin A. PMID- 1611354 TI - Treatment of depression in primary care. PMID- 1611356 TI - Asthma in general practice. PMID- 1611357 TI - Videotaped interviews with children suspected of being sexually abused. PMID- 1611358 TI - Maternity services. PMID- 1611359 TI - Beware shifts in case mix under the block contract. PMID- 1611360 TI - Adoption in utero is the wrong term. PMID- 1611361 TI - Chromosomal abnormalities and fetal nuchal translucency in first trimester. PMID- 1611362 TI - Health and safety at fairgrounds. PMID- 1611363 TI - Small bowel transplantation. PMID- 1611364 TI - Audit in general practice. PMID- 1611365 TI - Thinking through a salaried service for general practice. PMID- 1611366 TI - Warning signals from Oregon. PMID- 1611367 TI - Expectations of assisted conception for infertility. AB - OBJECTIVE: To provide reliable prognostic information for couples seeking assisted conception. DESIGN: Analysis of four years' practice (1988-91). SETTING: Private university service linked with NHS reproductive medicine services. PATIENTS: 804 couples with various causes of subfertility, median duration five years, median age of women 34 years. INTERVENTIONS: 1280 completed cycles: 950 in vitro fertilisation, 144 gamete intrafallopian transfer, and 186 intrauterine insemination and superovulation. MAIN OUTCOME MEASURES: Pregnancy and birth rates per cycle and cumulative pregnancy and take home baby rates per couple. RESULTS: In women under 40 years and men with normal sperm, whatever the cause of infertility, results with in vitro fertilisation improved steadily reaching a pregnancy rate per cycle of 30% (95% confidence interval 26% to 35%) during 1990 1 and birth rate per cycle of 29% (23% to 35%) in 1990. Pregnancy and birth rates for gamete intrafallopian transfer were 36% (28% to 44%) and 26% (17% to 37%) and for intrauterine insemination 18% (12% to 24%) and 16% (10% to 22%). After six cycles cumulative probability of pregnancy was 82% and cumulative take home baby rate 70%. Considering only in vitro fertilisation and gamete intrafallopian transfer after four cycles the pregnancy rate was 78% (66% to 91%). CONCLUSIONS: Conception is less likely in women over 40 and men with sperm dysfunction. For other couples the prognosis for a live birth is at least as good as for fertile couples if they persist with treatment. PMID- 1611368 TI - Review of company postmarketing surveillance studies. AB - OBJECTIVES: To review postmarketing surveillance studies sponsored by the pharmaceutical industry since the introduction of voluntary guidelines in 1987 and to evaluate their contribution to monitoring drug safety. DESIGN: Retrospective analysis of the information submitted to the Medicines Control Agency on postmarketing surveillance studies. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Study designs, projected and actual sample sizes, provision of interim and final reports, number of suspected serious adverse reactions reported, identification of new drug safety hazards. RESULTS: 31 studies had been conducted under the guidelines, of which 27 were prospective and four retrospective. Nine studies had at least one comparator group, the remainder were uncontrolled. The median projected sample size for the studies was 5600 patients. Only five studies had achieved at least 75% of the projected sample size. 11 studies had been abandoned, predominantly because of difficulties in recruitment, and 15 were ongoing. One study had identified an important new safety hazard. CONCLUSIONS: Company postmarketing surveillance studies have made only a limited contribution to the assessment of drug safety, principally because of weak study designs and difficulties in recruitment. The guidelines require modification to take this experience into account. PMID- 1611369 TI - Value of routine ultrasound scanning at 19 weeks: a four year study of 8849 deliveries. AB - OBJECTIVE: To evaluate the effectiveness of routine ultrasound scanning at 19 weeks' gestation in an unselected population in terms of accuracy of detection of fetal structural abnormality and the effect on obstetric and neonatal care. DESIGN: Prospective study over four years. Scans performed by radiographers with overall supervision by a radiologist. SETTING: Ultrasound department of district general hospital. SUBJECTS: All pregnant women were offered scans; 8523 of 8849 (96%) accepted. MAIN OUTCOME MEASURES: Information obtained from hospital records, genetic analysis, and post-mortem findings. RESULTS: 166 fetal anomalies occurred; 140 were detected at 19 weeks (sensitivity 85%; specificity 99.9%). In 27 cases fetuses were shown to have severely crippling or lethal abnormalities; termination of pregnancy was requested in 25. Early diagnosis influenced timing and place of delivery in babies with severe cardiac or gastrointestinal anomalies. CONCLUSION: Scanning at 19 weeks with availability of termination can reduce perinatal morbidity and mortality. Scanning can be performed in a general ultrasound department with adequate counselling facilities and close cooperation between radiographers, midwives, obstetricians, paediatricians, and the radiologist. PMID- 1611370 TI - Toxicity of norpethidine in sickle cell crisis. PMID- 1611371 TI - Prevalence of potential pathogens in cervical canal before termination of pregnancy. PMID- 1611373 TI - Medical audit in general practice. II: Effects on health of patients with common childhood conditions. North of England Study of Standards and Performance in General Practice. AB - OBJECTIVE: To estimate the effects of medical audit, particularly setting clinical standards, on patients' health. DESIGN: Before and after study strengthened by a replicated Latin square. SETTING: 62 training general practices in the north of England. PATIENTS: Random sample of 9000 children with any of five conditions--acute cough, acute vomiting, bedwetting, itchy rash, and recurrent wheezy chest--stratified by doctor consulted, condition, and age. INTERVENTIONS: Clinical standard set by each of 10 small groups comprising 84 general practitioner trainers for one randomly selected childhood condition. Each group also experienced a different type of medical audit, randomly selected, for each of the four other study conditions (receiving a clinical standard set by another trainer group, tabulated data comparing clinical performance with that of all other groups, tabulated data from only their own group, and nothing ("control" condition)). MAIN OUTCOME MEASURES: Condition specific, functional, psychological, and educational outcomes; together with parent satisfaction (recorded by home interviews and postal questionnaires). RESULTS: Children consulting trainers for recurrent wheezy chest after those doctors had set a standard for that condition improved both in drug compliance (79% (n = 33) before standard setting v 93% (30) after) and mean number of days of breathlessness (3.8 (SE 1.0) before v 1.7 (0.6) after) and wheeziness (4.7 (0.9) before v 1.8 (0.6) after), compared with those consulting doctors who had not (compliance 74% (144) before v 72% (146) after; breathlessness 2.4 (0.4) before v 2.3 (0.3) after; wheeziness 3.0 (0.4) before v 2.7 (0.4) after). There were no other significant effects of standard setting or audit on patients' health. CONCLUSION: Setting clinical standards improved drug compliance and respiratory function in children with recurrent wheezy chest. PMID- 1611372 TI - Medical audit in general practice. I: Effects on doctors' clinical behaviour for common childhood conditions. North of England Study of Standards and Performance in General Practice. AB - OBJECTIVE: To estimate the effects of medical audit, particularly setting clinical standards, on general practitioners' clinical behaviour. DESIGN: Before and after study strengthened by a replicated Latin square. SETTING: 62 training general practices in the north of England. SUBJECTS: 92 general practitioner trainers, 84 (91%) of whom completed the study; random sample of 3500 children consulting one of these trainers for any of five conditions--acute cough, acute vomiting, bedwetting, itchy rash, and recurrent wheezy chest--stratified by doctor consulted, condition, and age. INTERVENTIONS: Clinical standard set by each of 10 small groups of general practitioner trainers for one randomly selected childhood condition. Each group also experienced a different type of medical audit, randomly selected, for each of the four other study conditions (receiving a clinical standard set by another trainer group, tabulated data comparing clinical performance with that of all other groups, tabulated data from only their own group, and nothing ("control" condition)). MAIN MEASURES: Content of initial consultation divided into: history, examination, investigation, diagnosis, and management (abstracted from medical records and "enhancement forms" completed by doctors). RESULTS: There was increased prescribing of bronchodilators for acute cough, oral rehydration fluids for acute vomiting, antibiotics for itchy rash, and bronchodilators and oral steroids for recurrent wheezy chest and reduced prescribing of antibiotics for acute cough and recurrent wheezy chest and tricyclic antidepressants for bedwetting. Fewer children were "discharged." Each change was consistent with the standard and either limited to doctors who set a standard for that condition or significantly greater for them than all other doctors. CONCLUSION: Setting clinical standards improved prescribing and follow up. PMID- 1611374 TI - Managing change in primary care. Strategies for success. PMID- 1611375 TI - Statistical methods for assessing observer variability in clinical measures. PMID- 1611376 TI - Pollution most foul. PMID- 1611377 TI - Ovarian and cervical cancer. AB - Death rates from cervical cancer have already fallen this century and for patients with invasive cervical cancer five year survival rates are greater than for most solid tumours. Better screening for premalignant changes may further reduce the incidence of invasive cancer; indeed, it has been claimed that the reduction in mortality could be as high as 90%, though estimates of screening efficacy have varied greatly. For those with advanced invasive carcinoma neoadjuvant chemotherapy may reduce the risk of relapse and improve survival. PMID- 1611378 TI - Prevalence of HIV infection among drug users in Edinburgh. PMID- 1611379 TI - Transmission of HIV. PMID- 1611380 TI - Incidents involving exposure to blood. PMID- 1611381 TI - Incidents involving exposure to blood. PMID- 1611382 TI - Row over Maori cot death rate. PMID- 1611383 TI - What counts as cot death? PMID- 1611384 TI - Bovine spongiform encephalopathy and risk to health. PMID- 1611385 TI - Hospital admission and benzodiazepine use. PMID- 1611386 TI - Influence of early life on later health. PMID- 1611387 TI - Urine albumin, total protein, and glomerular proteinuria. PMID- 1611388 TI - Improving preregistration training. PMID- 1611389 TI - NCEPOD: more training needed. PMID- 1611390 TI - Decision analysis in medicine. PMID- 1611391 TI - Decision analysis in medicine. PMID- 1611392 TI - Keeping babies in prison. PMID- 1611393 TI - Decision analysis in medicine. PMID- 1611395 TI - The role of hospitals in the last year of people's lives. PMID- 1611394 TI - Paediatrics in the nineties: a time for change. PMID- 1611396 TI - Applications of hyperbaric oxygen. PMID- 1611397 TI - Imaging the eye with ultrasound. AB - The anatomical structure of the eye is accurately reproduced by the ultrasound B scan. When the light-conducting media are opaque, making ophthalmoscopy impossible, ultrasound scanning is the most practical and rapid method of obtaining images of the posterior segment, yielding information for diagnosis and preoperative planning. PMID- 1611398 TI - Current trends in the management of chronic myeloid leukaemia. AB - Conventional or alkylating treatment for chronic myeloid leukaemia has little impact on overall survival. Recent treatments, however, are encouraging. Alpha interferon may prolong the chronic phase in some patients, while allogeneic bone marrow transplantation is curative in over 50% of patients with HLA-compatible donors. PMID- 1611399 TI - Intravascular oxygenation with the IVOX. AB - Improvements in hollow fibre gas transfer membranes have enabled the development of an intravascular oxygenator which for the first time provides gas exchange without the need for an extracorporeal circuit. We describe all aspects of the clinical utilization of the intravascular oxygenator device. PMID- 1611400 TI - The public health physician and the provider. AB - A core strength of public health physicians is the ability to bring their skills to the integration of primary care, hospital medicine and local authority public health services. The current move towards a 'purchaser/provider split' is potentially damaging to this. PMID- 1611401 TI - Classification of affective disorders. AB - The classification of affective disorders has provoked much controversy in the past. Current classification systems, ICD-10 and DSM-IIIR, define operational criteria for diagnosis and recognize the presence of more chronic and milder forms. They reflect a growing consensus on the subject. PMID- 1611402 TI - Consent to treatment: what value consent forms? PMID- 1611403 TI - Overworking and overwaiting. PMID- 1611404 TI - Disagreement over the criteria for ARDS. PMID- 1611405 TI - Evidence of stress throughout the profession. PMID- 1611406 TI - Proceedings of the British Pharmacological Society Meeting. Tyne, 8-10 April 1992. Abstracts. PMID- 1611407 TI - Errors in young children's decisions about traffic gaps: experiments with roadside simulations. AB - Young children's vulnerability as pedestrians has often been attributed to deficiencies in their decision making about vehicle approach times. Some studies have found a preponderance of risky decisions below the age of eight years. In contrast, studies using a closer simulation of road crossing, known as the pretend road, have found a preponderance of overcautious decisions in young children: traffic gaps of adequate size were frequently rejected (missed opportunities). However, the pretend road has potentially distorting characteristics which may account for this divergent pattern of findings. The experiments reported below show that new simulations that eradicate distortions nevertheless validate the pattern of results produced with the pretend road. Differences between adults and young children were pronounced for missed opportunities, but not for risky decisions. Subsidiary analyses suggest that the risky decisions of the youngest children may have arisen through lapses in attention, rather than deficits in timing. These findings run contrary to the view that attributes young children's pedestrian vulnerability to perceptuo-motor deficiency. PMID- 1611408 TI - Police-schools liaison and young people's image of the police: an intervention evaluation. AB - This paper evaluates the impact of Police-Schools Liaison on young people's views and attitudes about the police and offending. It reports the first, large-scale, independent evaluation of this social intervention. The evaluation (based on 1245 secondary-school pupils) compares views of the police in schools with (target) and without (control) a full-time Schools Liaison Officer (SLO). Although attitudes to the police are marginally positive, they become less so over one year. There is no evidence that Schools Liaison input into the target schools slows or halts this decline, or that it affects perceptions of the seriousness of offences, and the likelihood of identification associated with crime. This weak impact is, at least in part, attributable to the low reported rates of direct contact, and the judged atypicality of the SLO. Target-school pupils judged their SLO positively, but as distinct from the 'police in general'. Their view of the SLO had a direct impact on their liking of the police in general, but there was no effect for contact. We conclude that Police-Schools Liaison has only limited positive effects, as predicted from critiques of the traditional 'contact hypothesis'. PMID- 1611409 TI - Gender-linked differences in everyday memory performance. AB - Recent research has demonstrated that people hold beliefs about how well others perform everyday memory tasks according to another's sex. For example, meta memory ratings indicate that other men and other women are believed to differ in their success at performing certain memory tasks (Crawford, Herrmann, Holdsworth, Randall & Robbins, 1989). In the present study, two experiments investigated whether gender stereotypes concerning everyday memory have any validity. Experiment 1 presented female and male subjects with two tasks that the aforementioned meta-memory ratings had shown are implicitly gender marked: learning a shopping list (a sterotypically feminine task) and learning directions to go to a particular place (a stereotypically masculine task). The results were consistent with the gender stereotypes, i.e. women recalled more of the shopping list than men whereas men recalled more of the directions than women. The second experiment investigated whether memory performance would be influenced by mere changes in the label of materials in memory tasks to be biased toward male or female gender background: labelling a shopping list as pertaining to 'groceries' or to 'hardware store'; and a set of directions to 'make a shirt' or to 'make a workbench'. The results also indicated that memory performance varied in ways consistent with gender stereotypes. PMID- 1611410 TI - The general intelligence and spatial abilities of gifted young Belgian chess players. AB - Thirty-three tournament-level young Belgian chess players aged 8 to 13 were tested with the French WISC (Wechsler Intelligence Scale for Children). The mean full scale IQ = 121, verbal IQ = 109 and performance IQ = 129. The results suggest that a high level of general intelligence and of spatial ability are necessary to achieve a high standard of play in chess. The high spatial ability of these young chess players suggested by the high performance IQs may go some way towards explaining why males tend to be more numerous than females among high standard chess players. PMID- 1611411 TI - On the determinants of persistent gambling behaviour. I. High-frequency poker machine players. AB - Persistent gambling was studied as a function of the reinforcement of arousal and winning during normal poker machine playing sessions. Play rate, heart rate, winnings, subjective excitement and expectations of winning were recorded for five male and five female high-frequency players. Autoregressive regression analysis indicated that wins affect play rate for up to three minutes, while effects of the other variables were inconsistent. Markov chain analysis confirmed that wins smaller than 50 credits tend to elevate play rate, while larger wins cause a breakdown in the otherwise very regular rate of play. Results are discussed in relation to the development of impaired control of gambling behaviour. PMID- 1611412 TI - Influence of time of 24-hour day on depth of processing in recall memory. AB - In this paper we report hourly variations in recall of words in a short-term memory task. Tests were carried out at 18.00, 22.00, 02.00 and 06.00 hours. The words to be memorized were preceded by a question designed to shape the type of encoding adopted by the subjects. The question concerned semantic, typographic or structural characteristics of the word. After presentation of all the words, the subjects were tested in free recall. Time of day had no effect on overall recall scores. Nevertheless, we observed a phase difference in the recall of items processed at superficial or deep levels. Items encoded by typographical attributes were more readily recalled at 02.00 than at 18.00, whereas semantically encoded words were less well recalled at night than during the day. There was also an interaction between the serial position of the items and time of day. At 22.00 and 02.00, subjects recalled words from the end of the list better. The results are discussed in terms of resource allocation models. PMID- 1611413 TI - Reduction of alcohol-induced performance impairment by prior ingestion of food. AB - The study examined the effectiveness of eating a meal prior to drinking alcohol as a means of reducing both peak blood alcohol level (BAL) and alcohol-induced performance impairment. In a separate-groups design, 133 male volunteers either fasted or received a standard meal of fixed calorific value and composition. Alcohol was then administered as placebo or at doses to achieve a BAL of 0, 20, 40 or 80 mg/100 ml. Subjects performed a dual task of primary tracking and secondary reaction time, short-term memory, five-choice reaction time and critical flicker fusion. Alcohol significantly impaired dual task performance but impairment was significantly reduced for those subjects who had eaten beforehand. BAL was also significantly lower in such subjects. It was concluded that prior ingestion of food might reduce the adverse effects of alcoholic intoxication, although performance remained impaired relative to the sober state. PMID- 1611414 TI - The basal turn of the cochlea. AB - The coils of the cochlea are now readily demonstrated by thin-section high resolution computed tomography (CT) in the axial plane. This assessment has become important in severely deaf patients who are candidates for cochlear implant surgery. The commonest abnormality shown in these cases is post meningitic or tympanogenic labyrinthitis ossificans, which can obstruct the passage of the electrode. Severe otosclerosis can cause a similar problem. Congenital deformities of the labyrinth are rarely suitable for implantation, but the procedure may be indicated for the true Mondini deformity. Implantation is contraindicated for severe dysplasia of the cochlea and for the recently described variety of x-linked deafness with deficient bone at the fundus of the internal auditory meatus. PMID- 1611415 TI - Magnetic resonance imaging of extracranial head and neck tumours. AB - The role of magnetic resonance imaging (MRI) in the investigation of head and neck tumours (excluding those primarily arising from the central nervous system or orbits) has been investigated. Follow-up data were obtained on 45 scans on 42 patients. MRI provided significant additional information compared with computed tomography (CT) in nine out of 17 (53%) scans performed for staging purposes. In the assessment of 19 patients with suspected tumour recurrence, MRI demonstrated a sensitivity of 100%, a specificity of 80% and an accuracy of 89%. PMID- 1611416 TI - The role of 3D CT in the assessment of acetabular fractures. AB - A total of 16 patients with acetabular fractures were evaluated by plain radiography, axial computed tomography (CT) and three dimensional (3D) CT. It was possible to classify the fracture type in each case from the plain radiographs alone. Axial CT gave additional detail in certain areas, notably the region of the teardrop, the obturator foramen and the acetabular roof. Intra-articular and impacted roof fragments and associated soft tissue injuries were also shown. 3D CT provided the best and most easily interpreted overall assessment of the fractures. In addition to projections equivalent to the plain radiographs, two other views were of particular clinical value in demonstrating surgically inaccessible areas, namely the view of the pelvis from above and the view of the inner aspect of the fractured hemipelvis. However, fracture lines demonstrated on plain radiographs and axial CT were not always apparent on the 3D CT scans. Although 3D CT is a valuable addition to the imaging of acetabular fractures, it is not a substitute for good quality plain radiography and analysis of the axial CT images. PMID- 1611417 TI - Hydatid disease of the liver: evaluation of ultrasound and computed tomography. AB - We have evaluated computed tomography (CT) and ultrasonography (US) in 41 patients with hepatic hydatid disease. CT was diagnostic in all patients, while US performed on 36 patients was diagnostic in 34. In the remaining two cases, heavy calcification in one and a large amount of intracavitary air in the other prevented accurate diagnosis. The US findings in the liver regarding cyst form (multilocular or unilocular), size and location were comparable to those of CT. CT detected associated extrahepatic cysts in the abdomen and pelvis in 11 patients while US performed on the same group of patients detected such cysts in seven patients. It is suggested that the entire abdomen and pelvis should be scanned in patients suspected of hydatid disease and when a hepatic lesion is suggestive of the disease. PMID- 1611418 TI - The spine deformity index in osteoporosis is not related to bone mineral and ultrasound measurements. AB - In 34 female patients suffering from osteoporotic vertebral compression fractures, the spine deformity index (SDIM) was determined, according to the method of Minne et al (1988), to reflect the radiological severity of established osteoporosis. Peripheral (single-photon absorptiometry (SPA) of the non-dominant distal forearm) and axial (quantitative computed tomography (QCT) of the lumbar spine) bone mineral measurements, as well as the broadband ultrasound attenuation of the os calcis, were performed in the osteoporotic patients and in a control group of 20 age-matched women. No correlation could be found between bone mineral measurements and radiological severity of osteoporosis, expressed as SDIM. All three densitometry methods showed clearly reduced values in patients with vertebral crush fractures. Correlations established in the control group between peripheral and axial bone mass (SPA versus QCT) could no longer be found in the osteoporotic group, thus indicating changes in bone mineral density of the spine after the occurrence of osteoporotic fractures. Our data show that SDIM is an additional parameter of osteoporotic change in the spine, independent from bone mass measurements. In the management of osteoporotic patients, quantitative radiological methods (i.e. SDIM) in addition to densitometry might be of value for grading and monitoring the progress of disease. PMID- 1611419 TI - Computed tomography in abdominal trauma: an audit of usage and image quality. AB - The use and quality of computed tomography (CT) in the evaluation of blunt abdominal trauma has been assessed by a retrospective review of 122 patients referred in the first 8 years following the installation of CT of the body. The referral patterns were analysed, and the quality of the images was assessed, with particular reference to unsatisfactory (unacceptable or poor) images. Referrals increased over the 8 years following installation. A large proportion of these examinations were performed outside normal working hours (58/122, 48%). In 64 out of 122 (52%) of examinations the images were considered of unsatisfactory quality with inadequate use of intravenous contrast medium cited as the most common cause for unsatisfactory examinations. Image quality did not improve with time. Image quality was unsatisfactory in a larger proportion of those examinations performed outside normal working hours (35/58, 60%) than those during the routine working day (29/64, 45%), although this difference did not reach statistical significance (0.1 greater than p greater than 0.05). Fewer unsatisfactory examinations were produced by a system dedicated to body CT (31/74, 42%) than by a neuroradiological system (33/48, 69%) (p less than 0.01). The proportion of unsatisfactory abdominal examinations was lower when the CT study concentrated on the abdomen (26/65, 40%) than when multiple regions (head, chest, abdomen, etc.) were examined (38/57, 67%) (p less than 0.01). This audit revealed many unsatisfactory examinations. In order to complete the audit loop we have addressed many of the contributory factors. A new CT system now provides images of high quality and is used for all abdominal work. Guidelines, which describe an optimized technique, have been issued to radiographers and radiologists. In particular, we have emphasized that there is no place for a poorly supervised "quick look" at the abdomen following a cranial or thoracic study. PMID- 1611420 TI - Quality assurance of computer controlled radiotherapy treatments. AB - There is a need in conformal therapy, as in any radiation therapy, for adequate quality assurance of the treatment plan and the delivery of the treatment. This paper examines quality assurance of two methods of conformal treatment, on a cobalt treatment unit using computer control. Each of the two methods demonstrates a different aspect of computer controlled treatments. Following completion of each treatment plan, an additional "quality assurance plan" is prepared. This is used to assess the integrity of the treatment plan, and the precision with which the computer controls the treatment unit. A simple method, using solid state detectors in a Perspex phantom, is used to validate the dosimetry of the "quality assurance plan". Quality assurance of the computer control is performed daily prior to treatments. At each treatment, parameters identifying the start position and final position of the computer controlled couch movements and the exposure time are noted by the radiographers. Comparison of the recorded movement of the treatment couch and the exposure time with that intended during each course of treatment has demonstrated, inter alia, limitations on couch speed control at speeds of less than 10 mm per min. PMID- 1611421 TI - New evidence that tamoxifen does not induce osteoporosis: a nuclear activation analysis and absorptiometry study. AB - The possibility of increased risk for osteoporosis in breast cancer patients treated with tamoxifen was investigated. 26 patients aged 41-65 years without skeletal metastases were studied. All patients were treated with 20 mg/d tamoxifen for a mean time of 22 months. The data obtained by in vivo neutron activation analysis of the phosphorus content in hands, were supplemented with data obtained by single photon absorptiometry in the forearm and radiographic morphometry. Comparison of the data with that of age and sex matched normal controls showed that breast cancer patients treated with tamoxifen are not prone to osteoporosis. PMID- 1611422 TI - Radical treatment of angiosarcoma of the scalp using megavoltage electron beam therapy. AB - Angiosarcoma of the scalp is a multifocal neoplasm that is often initially managed by wide excision and surgical reconstruction. Invariably, adjuvant radiotherapy is required to improve local control. Primary radical radiotherapy to the scalp is not well documented. The major limitation is the technical problem of treating homogeneously an extensive superficial curved volume. We describe a practical technique that can be administered with a standard linear accelerator capable of high-energy electron production. The technique uses a multiple abutted fixed field set-up at constant source to surface distance and the patient is immobilized in a custom wax helmet which also serves to optimize the electron absorbed dose in the treatment volume. Surgical excision and reconstruction is reserved for the salvage of local relapse. PMID- 1611423 TI - Quantitative analysis of CT brain images: a statistical model incorporating partial volume and beam hardening effects. AB - The purpose of this study was to construct and evaluate a statistical model for the quantitative analysis of computed tomographic brain images. Data were derived from standard sections in 34 normal studies. A model representing the intracranial pure tissue and partial volume areas, with allowance for beam hardening, was developed. The average percentage error in estimation of areas, derived from phantom tests using the model, was 28.47%. We conclude that our model is not sufficiently accurate to be of clinical use, even though allowance was made for partial volume and beam hardening effects. PMID- 1611424 TI - The Reference Man in diagnostic radiology dosimetry. AB - Following the legislation for radiation protection in Europe, increasing interest has been given to patient dosimetry in diagnostic radiology. Dose comparisons between groups of patients have demonstrated considerable discrepancies. The equipment, as well as the procedures used, have been scrutinized in order to find the reasons for the variation and to reduce it. In this work, patient size and shape are considered in patient dose evaluations in diagnostic radiology. The size, shape and constitution of the patients are shown to relate exponentially to the energy imparted during examination of the trunk. The equivalent cylindrical diameter of the patient body is used as the independent variable. Exponential functions are created by linear regression. The ICRP Reference Man with an equivalent diameter of 22.9 cm is used as a body-size standard. A method is suggested by which coordinate transformations reduce data to a base line defined by the Reference Man. It is shown that the method reduces the range of energy imparted by between 30% and 60% for six common X-ray examinations of the trunk. Resulting data constitute a finer instrument for intercomparisons between hospitals for the same examination. Further, it is suggested that adipose tissues should not be included when detrimental effects of radiologic exposure are determined. The Reference Man, stripped of 10 kg subcutaneous adipose tissue, is used as the non-fat standard dimension corresponding to the equivalent cylindrical diameter 21.2 cm. The suggested method is used to estimate the fraction of energy imparted to vital organs only. The results show that the energy imparted is reduced by between 30% and 60% according to this model. Consequently, predicted deaths are reduced by the same amount. PMID- 1611425 TI - Calibration of a 0.08 Tesla magnetic resonance imager for in vivo T1 and T2 measurement. PMID- 1611426 TI - The disappearing bladder--modifying imaging techniques after rectal excision. PMID- 1611427 TI - Magnetic resonance imaging and treatment of an unusual seminoma metastasis occurring in the parasellar region. PMID- 1611428 TI - 99Tcm HMPAO SPECT in progressive multifocal leucoencephalopathy. PMID- 1611429 TI - Increased attenuation value of a colloid cyst of the third ventricle following ventricular decompression. PMID- 1611430 TI - Diagnosis and treatment of an oesophageal stricture due to lichen planus. PMID- 1611431 TI - Case of the month. An underdiagnosed abdominal mass? PMID- 1611432 TI - The value of transvaginal scanning in the assessment of second trimester oligohydramnios. PMID- 1611434 TI - Altered radiotherapy fractionation in medulloblastoma. PMID- 1611433 TI - Biliary dilatation and pseudo-tumour of the liver. PMID- 1611435 TI - Primary aldosteronism. PMID- 1611436 TI - Screening for large bowel neoplasms in individuals with a family history of colorectal cancer. AB - Logistical problems associated with population screening for colorectal cancer are identified and the possibility of targeting screening to those with a familial predisposition to the disease is discussed. Evidence for a substantial genetic effect on the overall incidence of colorectal cancer is reviewed. The screening detection rate of colorectal neoplasms in relatives of patients with colorectal cancer has been shown to be higher than that expected in a non selected population; the evidence that polypectomy will reduce future colorectal cancer risk in such individuals is explored. Recent advances in the molecular genetics of colorectal cancer susceptibility are reviewed; it is possible that a genetic test might be developed in the future which could identify at least a proportion of those at risk. Excluding financial considerations, the risk-benefit ratio of colonoscopy in a screened population is intimately related to the remaining risk of colorectal cancer in those who undergo the examination. At present, patients undergoing colonoscopy to investigate a positive faecal occult blood (FOB) test as part of a population-based screening programme include individuals with a familial predisposition as well as those without. About 20 per cent of all cases of colorectal cancer are associated with an obvious genetic predisposition, and the risk of cancer in their relatives is high. Because false positives occur with Haemoccult, the residual risk to the population who are FOB positive but do not have a familial trait may be sufficiently low that the dangers of colonoscopy could outweigh the potential benefits. Scotland has a high incidence of colorectal cancer, and analysis of recent Scottish incidence data shows an actuarial lifetime risk of developing this disease of one in 23 for men and one in 33 for women. As a family history of the disease increases that risk by two to four times and the neoplasms arise throughout the colon in such a group, there may be a case for offering colonoscopy to all first-degree relatives of those under 50 years of age at diagnosis, if not of all index cases of colorectal cancer. PMID- 1611437 TI - Mechanism of action of external compression on venous function. AB - Compression stockings and bandages have been shown to improve venous haemodynamics and may act by reducing venous reflux. The aim of this study was to assess the mechanism of action of compression therapy on venous function and to determine whether such treatment may correct valvular incompetence. Both lower limbs of 36 patients (median age 59 (interquartile range 45-65) years) were assessed by duplex ultrasonographic scanning. There were 17 limbs with popliteal vein reflux, 19 with long saphenous vein (LSV) reflux and 21 with short saphenous vein (SSV) reflux. A water-filled adjustable pressure cuff was applied around the knee and inflated gradually, while continuously assessing the veins for reflux using ultrasonographic imaging. The external pressure applied by the cuff was noted when reflux was abolished or when the vein was completely occluded. In four (24 per cent) of 17 popliteal veins, eight (42 per cent) of 19 LSVs and three (14 per cent) of 21 SSVs reflux was abolished before occlusion of the vein. The cuff pressures required to achieve restoration of valvular function were significantly lower than those required to occlude the veins. It is possible, in some refluxing veins, to correct valvular dysfunction by external compression therapy. Coaptation of valvular cuffs to restore valvular competence may be the mechanism of action of compression therapy in venous disease. PMID- 1611438 TI - Angioscope-guided neodymium yttrium-aluminium-garnet laser valvulotomy for in situ vein bypass. AB - Valvulotomy for in situ vein bypass is commonly performed with a valvulotome. Although the procedure can be controlled through an angioscope, the dangers of intimal damage and valve remnants remain. An experimental study was designed to evaluate angioscopic laser valvulotomy compared with standard mechanical valvulotomy (n = 16). Two different laser probes, a bare 400-microns fibre (n = 20) and a 2-mm hot-tip (n = 26) were tested. Results were investigated by histology and scanning electron microscopy. Hot-tip laser valvulotomy achieved significantly better results than the 400-microns fibre. The Insitucat valvulotome yielded the worst results, with valve remnants in all cases and an 88 per cent rate of intimal damage. It is concluded that laser valvulotomy can be performed simply and safely with a very low incidence of valve remnants and intimal damage. PMID- 1611439 TI - Dermatan sulphate: a safe approach to prevention of postoperative deep vein thrombosis. AB - To assess the efficacy and safety of dermatan sulphate (MF 701) in preventing postoperative deep vein thrombosis (DVT), 324 patients aged 40 years or over undergoing elective major general surgical operations were included in a randomized trial comparing MF 701 (100 mg intramuscularly once a day) with unfractionated calcium heparin (UFH, 5000 units subcutaneously three times daily). Both treatments were initiated before operation and continued until discharge. In all, 316 patients were included in the analysis (MF 701, 157; UFH, 159). Serial impedance plethysmography was performed in all patients; a 125I radiolabelled fibrinogen uptake test was added to impedance plethysmography in a randomized subsample of 62 patients (MF 701, 28; UFH, 34). Positivity in either test was confirmed where possible by venography. DVT was diagnosed by venography or, when this could not be performed, by positivity of either impedance plethysmography or fibrinogen uptake test. The incidence of DVT was 3.1 per cent (patients receiving MF 701) and 1.6 per cent (those receiving UFH) in patients undergoing impedance plethysmography alone, and 7.1 and 11.8 per cent, respectively, in those undergoing both impedance plethysmography and fibrinogen uptake test; in neither case was the difference between treatments statistically significant. There were five in-hospital deaths, two in patients receiving MF 701 and three in patients on UFH. The incidence of clinically overt haemorrhage was 5.7 per cent in patients on MF 701 and 17.6 per cent in those on UFH (P less than 0.01). Postoperative transfusions and reoperations due to bleeding were significantly less frequent in patients receiving MF 701. Mortality rates at 3 months were similar for the two treatment groups. Compared with standard prophylaxis using UFH, MF 701 showed a similar efficacy with a significantly greater safety. PMID- 1611440 TI - Infected femoral pseudoaneurysm in intravenous drug abusers. AB - The result of surgical treatment of 21 infected femoral pseudoaneurysms in 19 intravenous drug addicts was evaluated. Eight pseudoaneurysms involved only the common or superficial femoral artery and 13 involved the femoral bifurcation. Excision and ligation was performed as the sole procedure in 19 instances, and revascularization by bypass through the obturator route was carried out in two. The mean follow-up was 12.3 months. One patient required an above-knee amputation. The resultant ischaemia was greater after triple vessel ligation (mean ankle:brachial pressure index (ABPI) 0.41) than single vessel ligation (mean ABPI 0.58). Postoperative bleeding occurred in one patient. Intermittent claudication was present in 14 patients after excision and ligation. Claudication was universal and more severe after triple than after single vessel ligation. There was no subsequent limb loss. Excision and ligation is safe and is the treatment of choice for infected femoral pseudoaneurysm in drug addicts. PMID- 1611441 TI - Postoperative infection and natural killer cell function following blood transfusion in patients undergoing elective colorectal surgery. AB - The frequency of infection in 197 patients undergoing elective colorectal surgery and having either no blood transfusion, transfusion with whole blood, or filtered blood free from leucocytes and platelets was investigated in a prospective randomized trial. Natural killer cell function was measured before operation and 3, 7 and 30 days after surgery in 60 consecutive patients. Of the patients 104 required blood transfusion; 48 received filtered blood and 56 underwent whole blood transfusion. Postoperative infections developed in 13 patients transfused with whole blood (23 per cent, 95 per cent confidence interval 13-32 per cent), in one patient transfused with blood free from leucocytes and platelets (2 per cent, 95 per cent confidence interval 0.05-11 per cent) and in two non-transfused patients (2 per cent, 95 per cent confidence interval 0.3-8 per cent) (P less than 0.01). Natural killer cell function was significantly (P less than 0.001) impaired up to 30 days after surgery in patients transfused with whole blood. These data provide a strong case against the use of whole blood transfusion in patients undergoing elective colorectal surgery. PMID- 1611442 TI - Gastrointestinal tract perforation in children due to blunt abdominal trauma. AB - Over a 14-year period 587 children under 13 years of age were admitted with blunt injury to the abdomen. Twenty-nine (4.9 per cent) of these were found to have bowel rupture. Evidence of peritonitis was present at initial evaluation in 11 children (38 per cent). Radiological evidence of perforation (pneumoperitoneum) was present in only five of 27 (19 per cent) with a further six of 27 (22 per cent) showing dilated loops of bowel or fluid levels. Thus 59 per cent of radiographs were not diagnostic. The mean time from admission to laparotomy was 17 h. Proximal bowel perforation was common and perforation at multiple sites occurred in five patients; 59 per cent had a concomitant injury which resulted in two deaths (from head injury). Initial clinical and radiological evidence of bowel perforation can be misleading and reliance on such indicators may result in significant diagnostic delay. Frequently repeated clinical examination is advocated; progression of abdominal signs should alert the clinician to proceed to laparotomy. PMID- 1611443 TI - Effect of antibiotics in fibrin sealant on healing colonic anastomoses in the rat. AB - In 90 rats a colonic anastomosis was constructed with 12 interrupted 7/0 polypropylene sutures. Group 1 (n = 30) served as a control group. In group 2 (n = 30) the anastomosis was sealed with fibrin adhesive and in group 3 (n = 30) a mixture of fibrin, clindamycin and cefotaxime was used. On days 2, 4 and 7, ten animals in each group were killed. Adhesion formation was significantly increased in groups 2 and 3 compared with the control group. On day 2 the anastomosis was significantly stronger after sealing with antibiotic-fibrin mixture. On day 4 the bursting pressure in group 2 was significantly lower than in groups 1 and 3. At the same time the concentration of hydroxyproline was significantly reduced in group 2, but not in group 3. The addition of antibiotics prevents the negative effect of fibrin adhesive on the healing colonic anastomosis and contributes to a stronger anastomosis on day 2 after operation. PMID- 1611444 TI - Functional evaluation of the intrathoracic stomach as an oesophageal substitute. AB - A study of duodenogastric reflux and gastric function was undertaken in 16 patients 1-7 years after oesophagectomy and high intrathoracic oesophagogastrostomy for oesophageal carcinoma. All were able to eat satisfactorily; ten complained of mild foregut symptoms and ten had endoscopic mucosal lesions. Biliary excretion scintigraphy demonstrated pathological duodenogastric reflux in 11 patients. The emptying of a semisolid radiolabelled meal from the intrathoracic stomach in the upright position was significantly quicker than in control subjects (P less than 0.01). No gastric motor activity was recorded on manometry, suggesting that the transposed stomach acts like an inert tube. Results of 24-h pH monitoring showed that the area under the curve at pH less than 4 in the stomach was significantly less than in control subjects (P less than 0.001). In addition, patients had a significantly greater oesophageal alkaline exposure (P less than 0.001). The vagotomized intrathoracic stomach therefore empties well in the upright position, but is subjected to reflux of alkaline duodenal contents and can retain the ability to produce acid. The interaction between alkaline and acid contents in the pathogenesis of symptoms and mucosal lesions needs further investigation. PMID- 1611445 TI - Thoracoscopic long oesophageal myotomy for nutcracker oesophagus: initial experience of a new surgical approach. AB - A thoracoscopic technique is described for the execution of long oesophageal myotomy for nutcracker oesophagus causing odynophagia and non-cardiac chest pain. The technique is based on a multipuncture method and a left thoracoscopic approach. It has been performed on three patients with complete symptomatic relief in the short term, although the follow-up period is short (maximum 12 months). No complications were encountered and discharge from hospital occurred by the fifth day after operation. PMID- 1611446 TI - Management of empyema thoracis at Lusaka, Zambia. AB - Of the 39 consecutive patients with empyema thoracis managed by one of the five general surgical units at Lusaka, Zambia, 26 suffered from human immunodeficiency virus (HIV) infection and 19 were diagnosed as suffering from pulmonary tuberculosis within 3 years of developing empyema thoracis. Thirty patients were between 16 and 40 years of age; of these, 22 suffered from acquired immune deficiency syndrome (AIDS) and all 19 patients with pulmonary tuberculosis belonged to this age group. Of the four patients with empyema thoracis in the age group of 0-5 years, two were suffering from AIDS. The majority of cases of empyema thoracis associated with AIDS present insidiously and, because of late presentation, rib resection is necessary. After surgery these patients were managed at home with the help of a home care team, thus reducing the burden on hospital resources. The morbidity and mortality rates in these patients are higher than in those in whom empyema thoracis is not associated with AIDS. PMID- 1611447 TI - Early gastric cancer. AB - Early gastric cancer comprises more than 30 per cent of gastric carcinomas treated in Japan but remains an uncommon entity in the western hemisphere. A retrospective review of 48 patients with early gastric cancer undergoing operative treatment between 1965 and 1984 was carried out. The mean patient age was 70 years, in 31 men and 17 women. Preoperative diagnosis was made in 88 per cent of patients undergoing oesophagogastroduodenoscopy with biopsy but upper gastrointestinal radiography was diagnostic in only 20 per cent. Surgical management consisted of subtotal gastrectomy (86 per cent), total gastrectomy (10 per cent) and wide local excision (4 per cent). The operative mortality and morbidity rates were 0 and 38 per cent, respectively. Mean follow-up was 7.7 years, with 44 per cent of patients still alive. Multivariate analysis disclosed only a healthy Eastern Cooperative Oncology Group score (P = 0.002) and a diploid DNA tumour pattern (P = 0.05) as significant prognostic variables of survival. The overall survival rate of patients with early gastric cancer (70 per cent at 5 years) was equivalent to that of an age- and sex-matched control population. PMID- 1611448 TI - Dismantling of a gastroenterostomy in the management of alkaline reflux gastritis. PMID- 1611449 TI - Surgery in tropical pancreatitis: analysis of risk factors. AB - Over a 7-year period, 91 patients with tropical pancreatitis underwent operation for intractable pain. Univariate and multivariate analyses were performed to identify factors correlating with mortality, major complications, poor pain relief and associated malignancy. Patients with benign disease (group 1, n = 72) had longer survival than those with superimposed malignancy (group 2, n = 19). Pain relief was better in group 1 (59 patients compared with none, P less than 0.01). Age above 40 years, short duration of symptoms, mass lesions on ultrasonography and main pancreatic duct obstruction on endoscopic retrograde pancreatography were associated with a high risk of cancer. After reoperation major complications (four of ten) or death (three of ten) occurred more commonly than after primary procedures (seven of 81, P = 0.019 and five of 81, P less than 0.05, respectively). Poor pain relief in group 1 patients was more common after incomplete clearance of main duct stones (four of 13 versus three of 53, P less than 0.01) and after short length ductotomy (three of eight versus four of 58, P less than 0.01). Tropical pancreatitis has a high association with pancreatic adenocarcinoma. Wide ductotomy, stone clearance and drainage gave good symptomatic results in patients with benign disease. Overall results were poor in patients with cancer. PMID- 1611450 TI - Endoscopic sphincterotomy in young patients with choledochal dilatation and a long common channel: a preliminary report. AB - An anomalous elongated pancreaticobiliary common channel encourages reflux up both the biliary tree and the pancreatic ductal system, resulting in progressive choledochal dilatation, cholangitis with ductal calculi, relapsing pancreatitis and malignant change. Transduodenal sphincteroplasty has been used to improve drainage from the abnormal channel. The use of endoscopic sphincterotomy (ES) to establish drainage and minimize the surgical risks is reported in six symptomatic patients with mild choledochal dilatation (common bile duct diameter less than 15 mm), a common channel less than 15 mm in length and a distal stenosis. This was successful in five patients, who have no further symptoms. ES failed in the only patient with an undilated common channel and this patient went on to have open surgery. We believe ES to be safe and effective in the treatment of selected cases of long common channel. PMID- 1611451 TI - Body water compartments in patients with obstructive jaundice. AB - To elucidate the pathogenesis of renal dysfunction associated with obstructive jaundice, body water compartments were measured using a multi-isotope dilution technique in ten patients with biliary tract obstruction and in ten control subjects matched for age, sex, weight, height and body surface area. Expressed as a fraction of body-weight, total body water was reduced in jaundiced patients (41.8 versus 46.2 per cent, P less than 0.02). Extracellular water volume was also reduced in patients with jaundice (20.3 versus 24.3 per cent, P less than 0.003) owing to a reduction of the interstitial space (16.1 versus 19.5 per cent, P less than 0.004) and, to a lesser degree, of the plasma volume (4.2 versus 4.8 per cent, P = 0.1). There was a close correlation in jaundiced patients between plasma volume and the creatinine clearance rate (r2 = 0.56, P less than 0.02) and between plasma volume and extracellular volume (r2 = 0.77, P less than 0.0001). Extracellular volume in such patients also correlated with the percentage weight loss (r2 = 0.42, P = 0.04). Obstructive jaundice is associated with a contracted extracellular water compartment, although extracellular water, as a percentage of body-weight, increased in proportion to the body-weight lost. Reduction of the interstitial volume and a marginally reduced plasma volume may be determinant factors in the pathogenesis of the renal and haemodynamic disturbances observed in patients with biliary tract obstruction. PMID- 1611453 TI - Clinical experience with adult polycystic liver disease. AB - Adult polycystic liver disease is characterized by multiple diffuse cystic lesions of the liver, usually in association with polycystic kidney disease. Rarely, significant liver disease will produce enough symptoms to call for surgical attention. Symptoms range from simple compression to fatal liver failure. Treatment of seven patients (six women) with symptomatic polycystic liver disease over 18 months is reported. Rapidly progressing liver failure and sepsis from infected ascites following puncture developed in one patient and precluded surgery. Another presented with an acute abdomen and anaemia from liver cyst bleeding and was treated conservatively. Five patients with massive hepatomegaly and compression symptoms underwent fenestration and resection to debulk the cystic liver mass. No intra-abdominal drains were used after operation and there were no hospital deaths. One patient developed a bile leak which was managed by percutaneous drainage. Clinical approach, complications and treatment options in adult polycystic liver disease are reviewed. PMID- 1611452 TI - Elective hepatic resection in the elderly. AB - This retrospective review assessed the safety and validity of elective liver resection in patients older than 64 years of age. In all, 293 patients underwent elective liver resection over a 23-year period (1967-1990). Fifty-two patients (18 per cent) were older than 64 (maximum 84, mean 70.4) years and all but four of these did not have cirrhosis. In this older subgroup, indications for resection were liver metastases in 30 patients, primary malignancy in 16, benign tumours in five and multiple abscesses in one. There were 21 major resections, with two deaths from hepatic failure, and 31 minor resections, with one death from cardiac failure (total mortality rate 6 per cent). During the same period, there were seven deaths after elective resections performed in 222 patients without cirrhosis who were younger than 64 years (P = 0.39). Mortality rate and duration of postoperative hospital stay were not related to the extent of liver resection nor to patients' grading according to the American Society of Anesthesiologists' criteria. Intraoperative blood loss was the only parameter found to influence mortality rate (P = 0.008) and duration of hospital stay (P = 0.04). Elective liver resection can be safely undertaken in elderly patients without cirrhosis, provided that intraoperative blood loss is minimized. PMID- 1611454 TI - Successful treatment of complete inferior vena cava thrombosis after liver transplantation by thrombolytic therapy. PMID- 1611455 TI - Strangulated small bowel hernia of the falciform ligament. PMID- 1611456 TI - Meconium ileus: a review 1972-1990. AB - This article reviews the management and mortality of 53 neonates with meconium ileus and cystic fibrosis treated in one paediatric surgical centre from 1972 to 1990. Forty-four patients (83 per cent) presented with simple meconium ileus and 26 of 40 patients in this group were successfully treated with Gastrografin enemas. Four patients suffered a perforation as a result of the enema (perforation rate 5 per cent). The 1-year survival rate for simple meconium ileus was 81 per cent and for complicated meconium ileus 75 per cent. PMID- 1611457 TI - Prepublic sinus: an unusual urachal remnant. PMID- 1611458 TI - Sitting a transverse colostomy. AB - Traditional teaching suggests that a transverse colostomy should be sited in the right upper quadrant. This study of 67 colostomies (26 right upper quadrant and 41 right iliac fossa) indicates that they should be placed in the optimum position for each patient, which is usually the right iliac fossa. PMID- 1611459 TI - Colonic anastomosis using the biofragmentable anastomotic ring and manual suture: a prospective, randomized study. AB - One hundred and fifty consecutive patients undergoing colonic surgery were randomized into two groups: 71 underwent hand-suture with a two-layer anastomosis of resorbable suture material (3/0 Dexon) and 79 were fitted with the biofragmentable anastomotic ring (Valtrac-BAR). Five patients, two treated using the BAR and three by suturing, developed anastomotic leakage which required a Hartmann-type reoperation. This was successful in four; one patient in the suture group died after reoperation. One patient who underwent suture had an early anastomotic stricture with fatal sequelae. Three other patients (one in the BAR group and two in the suture group) died after operation from other causes. Thus the mortality rate was 6 per cent in the suture group and 1 per cent in the BAR group. During follow-up, one patient in each group underwent reoperation for anastomotic stricture. Recovery of the gastrointestinal tract was similar in the two groups regarding duration of nasogastric drainage, intravenous fluid therapy and ileus. There was no difference between the groups in duration of hospital stay. The BAR seems to be a safe and reliable alternative to conventional suture anastomosis in colonic surgery. PMID- 1611460 TI - Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation. AB - The crypt cell production rate was measured in 14 patients with adenomatous colorectal polyps, 17 patients with colorectal cancer and 12 control subjects. The median (interquartile range) rate (cells per crypt per hour) was found to be significantly higher (P less than 0.001) in the polyp (2.45 (1.94-3.20)) and cancer (3.01 (2.35-3.68)) groups compared with controls (1.25 (0.70-1.85)). A double-blind cross-over study was performed in patients with adenomatous polyps consisting of 2 months' treatment, 2 weeks' washout, followed by 2 months' treatment with dietary calcium supplementation (1.25 g day-1) versus placebo. A significant reduction in the crypt cell production rate occurred with calcium treatment compared with the placebo (1.25 (0.6-2.25) versus 2.15 (1.58-3.08) cells per crypt per hour, P = 0.035). This study demonstrates a significant reduction in mucosal cell proliferation by dietary calcium supplementation in patients with adenomatous polyps. Such treatment may be worthy of further investigation in patients at high risk of developing colorectal polyps. PMID- 1611461 TI - Improving survival rates for patients with colorectal cancer. AB - Between 1 January 1984 and 31 December 1990, 575 patients were operated on for colorectal cancer. The surgical procedure was performed consistently and no patients were lost to follow-up. Almost half of the patients (284 of 575) had tumours of stage I or II, with 5-year survival rates over 90 per cent. After extending the resection margins in 28 cases of colonic carcinoma there has been no case of tumour recurrence. The overall 5-year survival rate for patients with colonic carcinoma was 81 per cent. Complete resection of the mesorectum was mandatory for rectal resection. One-third of the carcinomas in the lower third of the rectum could be resected with maintenance of bowel continuity and an abdominoperineal resection avoided. Not only was the tumour recurrence rate in the former patients lower (10.5 per cent) compared with that in those undergoing abdominoperineal resection (14.3 per cent) but the 5-year survival rate at 90 versus 52 per cent was significantly higher. The overall 5-year survival rate for patients with rectal carcinoma was 71 per cent. PMID- 1611462 TI - Haemorrhoids are associated not with hypertrophy of the internal anal sphincter, but with hypertension of the anal cushions. AB - A combined manometric and ultrasonographic study of the internal anal sphincter was carried out in 20 patients with haemorrhoids and 20 age-matched normal controls. Mean(s.e.m.) basal anal pressure was significantly higher in patients than in controls, 62(4) versus 45(6) cmH2O (P less than 0.05), although there were no significant differences in mean maximum basal and squeeze pressures. During rectal distension 90 per cent of patients showed no reduction in anal pressure in the outermost anal channel, although the internal sphincter electromyogram was suppressed and the external sphincter electromyogram did not necessarily increase above baseline. The mean(s.e.m.) maximum residual pressure was significantly higher in patients, 70(6) versus 45(6) cmH2O (P less than 0.05). Direct pressure measurement in anal cushions exhibited abnormally high median pressure in patients compared with controls, 35 versus 10 cmH2O (P less than 0.001). Pressures recorded during coughing and straining were also significantly higher in patients than in controls (P less than 0.001). Ultrasonographic study of the anal canal revealed a clear image of the internal sphincter, the thickness of which could easily be measured. The mean(s.e.m.) thickness of the sphincter was not significantly different, 2.3(0.2) versus 2.1(0.1) mm, between patients with haemorrhoids and controls (P = 0.18). The absence of any significant differences in the internal sphincter thickness between normal subjects and patients with haemorrhoids suggests that the high anal pressure in patients with haemorrhoids is of vascular origin. PMID- 1611463 TI - Quantitative measure of small vessel anastomotic contour using corrosion resin cast models. PMID- 1611464 TI - Sentence comprehension in Parkinson's disease: the role of attention and memory. AB - Sentence comprehension is a complex process involving at least attentional, memory, grammatical, and semantic components. We report three experiments designed to evaluate the impairments underlying sentence comprehension difficulties in nondemented patients with Parkinson's disease (PD). In the first experiment, we asked patients to answer simple questions about sentences which varied in terms of grammatical complexity and semantic constraint. We found that PD patients are significantly compromised in their ability to perform this task. Their difficulties became more prominent as grammatical complexity increased, but they were significantly assisted by semantic constraints that limited possible interpretations of a sentence. Analyses of individual patient profiles revealed heterogeneous performance across the group of PD patients and somewhat inconsistent performance for patients across testing sessions. In the second experiment, we tested the possibility that patients' heterogeneous performance on the sentence comprehension task is due to an impairment in memory or attention, cognitive domains known to be compromised in some PD patients. Although PD patients and control subjects differed on one memory measure, there were no significant correlations between attention and memory performance and the results of the sentence comprehension task. In the final experiment, we manipulated the sentences used in the first experiment in a fashion that stressed the need for memory and attention in a sentence. The results indicated that PD patients are significantly compromised in their ability to attend to certain critical grammatical features of a sentence. A regression analysis identified specific grammatical, semantic, and attentional mechanisms as significant contributors to PD patients' overall sentence comprehension, accounting for over 97% of the variance in their performance. We conclude that there are multiple sources of cognitive difficulty underlying PD patients' sentence comprehension impairment. PMID- 1611465 TI - Stuttering acquired from subcortical pathologies and its alleviation from thalamic perturbation. AB - Acquired stuttering subsequent to subcortical pathology of mesothalamus was observed in four neurosurgical subjects. The patients suffered from chronic pain, seizures, and somatosensory disorders. They also exhibited unpredictable and uncontrollable speech, spasmodic blocks which were devoid of accessory features, and adaptation effect. Therapeutic mesothalamic stimulation, used as a treatment of last resort to relieve the pain and associated symptoms, also had an ameliorating effect on the stuttering. Spontaneously occurring focal abnormal EEG discharges were anatomically delineated and used as a guide for therapeutic stimulation electrode placement. Attentuation of the abnormal discharges was followed by alleviation of symptoms. This investigation examines the clinical characteristics of stuttering in four neurosurgical patients and suggests an electropathologic basis for their mesothalamic-generated speech dysfluencies. The cooccurrence of pain, seizures, somatosensory disorders, and stuttering, and their concurrent amelioration, suggests that both chronic pain and stuttering may be implicated by similar or related reticular electropathologic generators, couched in overlapping reticular networks extending from the brain stem to the thalamus, and that the acquired stuttering may be recruited as one component of a larger syndrome complex. PMID- 1611466 TI - Recurrent fluent aphasia associated with a seizure focus. AB - The relationship between dominant hemisphere seizure activity and aphasia is unclear. Although speech arrest, expressive speech problems, and comprehension difficulties have often been associated with temporal lobe seizure activity, neologistic, paraphasic speech is rare. We report a patient with seizures following encephalitis who had recurrent episodes of fluent, severely aphasic speech with impaired comprehension which correlated with continuous, high voltage spike and slow wave activity in the left temporal region. During a several-day period of intermittent electrographic seizure activity, he had fluctuating receptive aphasia, and he developed transient paranoid psychosis following treatment. We discuss the behavioral manifestations of his left temporal seizures and correlate the changing nature of his behavior with therapeutic interventions. This case, as well as a review of others, suggests that paroxysmal fluent aphasia results from a partially treated electrographic seizure focus in the dominant temporal lobe. PMID- 1611467 TI - Processing complexity and sentence memory: evidence from amnesia. AB - This study examines sentence memory as a function of linguistic processing complexity in amnesic patients. Sentence length as well as lexical and syntactic complexity were manipulated in two sentence repetition experiments. It was found that the amnesic patients performed considerably worse than the control subjects and that performance decreased: (1) when sentence length was increased by the addition of adjuncts compared to arguments of the verb; (2) when the verb selected more thematic frames; and (3) when sentences involved "empty" argument positions that must be linked to antecedents, particularly across clausal boundaries. These data showed how linguistic complexity affects sentence memory and implied that the amnesic deficit did not involve a generalized difficulty for materials of similar length, rather, the deficit was specific to certain representational types and processing routines. PMID- 1611468 TI - Ultrastructural analysis of the serotonin hyperinnervation in adult rat neostriatum following neonatal dopamine denervation with 6-hydroxydopamine. AB - Serotonin (5-HT) immunocytochemistry was used at the electron microscopic level to characterize the ultrastructural features of 5-HT axon terminals (varicosities) hyperinnervating the neostriatum of adult rats, 3 months after a neonatal destruction of the nigrostriatal dopamine system by intraventricular 6 hydroxydopamine. 5-HT-immunostained terminals from the anterior half of the hyperinnervated neostriatum were examined in single thin sections, and compared to their counterparts in vehicle-injected controls with respect to shape, size, organelle content, presence of a synaptic membrane differentiation and composition of the microenvironment. The intrinsic and relational features of the 5-HT-immunostained varicosities were essentially the same in 5-HT-hyperinnervated and control tissue. In particular, the frequency with which these varicosities made synaptic contacts was similarly low in both conditions (6-8% for whole varicosities), as already described in normal adult rat neostriatum. The distributional frequency of elements juxtaposed to the 5-HT-immunostained varicosities was also comparable in control and 5-HT-hyperinnervated tissue. However, in both conditions, there were much fewer dendritic spines in the microenvironment of 5-HT varicosities than around unlabeled terminals randomly selected from the same thin sections. This difference seemed entirely due to the numerous axo-spinous synaptic contacts made by the randomly selected, unlabeled varicosities. Together with recent observations on the 5-HT-hyperinnervation of adult rat hippocampus after grafts of fetal neurons, these data lead to the suggestion that mostly non-junctional neostriatal 5-HT terminals are not committed to a specific intratissular microenvironment. This might in part explain why they grow in excess when reinnervating adult tissue after a lesion or a graft. PMID- 1611469 TI - Effect of histamine and antagonists on electrical resistance across the blood brain barrier in rat brain-surface microvessels. AB - The effect of histamine on blood-brain barrier permeability was investigated using in situ measurement of transendothelial electrical resistance in brain surface microvessels of anaesthetized rats. Mean resistance of vessels superfused with artificial cerebrospinal fluid was 1500 omega.cm2, indicating a tight barrier with low ion permeability. The addition of 10(-4) M histamine resulted in a 75% decrease in resistance, in both arterial and venous vessels, indicating a marked increase in barrier permeability. To determine the nature of the response to histamine, rats were given presurgical intraperitoneal injections of promethazine (H1 receptor antagonist), cimetidine (H2 receptor antagonist) or indomethacin (cyclo-oxygenase inhibitor), singularly and in combinations. Cimetidine completely blocked the histamine-mediated increase in barrier permeability whereas promethazine only had a small effect and indomethacin was ineffective. In addition, cimetidine treatment resulted in a 100% increase in basal resistance in both arterial and venous vessels, suggesting endogenous histamine was acting to increase blood-brain barrier permeability. It is concluded that histamine causes an increase in blood-brain barrier permeability which is mediated via endothelial H2 receptors, and that the electrical resistance in cimetidine-treated rats most closely represents the true permeability of the blood-brain barrier. PMID- 1611470 TI - Vasopressin and oxytocin in brain areas of rats selectively bred for differences in behavioral performance. AB - Wistar rats were selectively bred over 10 generations for differences in performance in a footshock-motivated brightness discrimination (BD) test in a Y maze. High behavioral performance (Wis/HBP) and low behavioral performance (Wis/LBP) rat lines were obtained which differ significantly in all behavioral components tested: frequency of correct responses, number of trials to criterion, response latency (HBP less than LBP), and frequency of freezing behavior (HBP less than LBP), the latter suggesting differences in emotionality. In Wis/LBP rats, furthermore, the normal increase in behavioral performance between the training and the relearning session, which indicates the formation of a memory trace, disappeared during selection. In male breeders sampled during selection of the two lines (Wis/HBP: n = 17; Wis/LBP: n = 21), both arginine vasopressin (AVP) and oxytocin (OXT) contents were measured by radioimmunoassay in the motor cortex, septum/striatum, hippocampus, hypothalamus, medulla oblongata and posterior pituitary. Compared with the Wis/HBP rats, the Wis/LBP rats contained less AVP in the hippocampus (3.1 +/- 0.58 vs 8.3 +/- 1.4 pg/mg wet wt., mean +/- S.E.M., P less than 0.001), but more AVP in the medulla (1.7 +/- 0.20 vs 1.1 +/- 0.18 pg/mg, P less than 0.05). In contrast, no significant differences between the lines were detected with respect to OXT concentrations. In the Wis/LBP rats, moreover, the hippocampal AVP content decreased during selection (r = -0.645, P less than 0.01), while the acquisition response latency increased (r = 0.549, P less than 0.01). As a consequence, a significant, albeit weak, negative correlation (r = -0.483, P less than 0.05) was observed between the individual hippocampal AVP content and the response latency during acquisition. Thus, the results confirm the view that genetically determined differences in the hippocampal content of endogenous AVP may contribute to an individual's level of emotionality and behavioral performance. PMID- 1611471 TI - The effect of bolus methylprednisolone in prevention of brain edema in hypoxic ischemic brain injury: an experimental study in 7-day-old rat pups. AB - One of the major mechanisms responsible for tissue injury in hypoxic ischemic brain damage is the formation of free radicals. We studied the efficacy of methylprednisolone, which is claimed to cause rapid congealing of membranes, and to protect the cells against the free radicals present in the environment, in preventing the brain edema that occurs in hypoxic ischemic brain injury. Hypoxic ischemic brain injury to the right hemisphere in 7-day-old rat pups is produced by cauterization of the right common carotid artery followed by hypoxia in 8% oxygen and 92% nitrogen for 3 h. The animals were divided into the groups. One group received methylprednisolone at 30 mg/kg body weight and the other an equal volume of saline 40 min before hypoxia. At 42 h of recovery, some of the rats were killed for measurement of water content in the right and left hemispheres whereas others were killed at 40 days for neuropathological examination. The water content in the right hemisphere was significantly lower in the 19 methylprednisolone-treated pups than it was in 20 saline-treated pups, mean +/- S.E.M. was 83.913 +/- 0.313% and 86.681 +/- 0.377%, respectively. The differences between the means were significant (P less than 0.001) according to the Mann Whitney U-test. The difference of the mean water contents between the two hemispheres was significantly higher in the saline-treated group (2.695 +/- 0.372%) than it was in the methylprednisolone-treated group (0.432 +/- 0.088%), P less than 0.0001 by independent samples t-test. Neuropathological study was performed on 4 rat pups.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611472 TI - Angiotensin II evokes noradrenaline release from the paraventricular nucleus in conscious rats. AB - In vitro and in vivo experiments have provided indirect evidence that some of the central actions of angiotensin II (ANG II) involve catecholaminergic pathways in the brain. In this study in conscious rats we investigated the effect of stimulation of periventricular ANG II receptors on blood pressure and on catecholamine release (microdialysis and HPLC) from the paraventricular nucleus (PVN), a hypothalamic area thought to be instrumental in the central pressor responses to ANG II through the release of vasopressin into the blood. Intracerebroventricular (i.c.v.) injections of pressor doses of ANG II (1 ng and 100 ng) led to significant dose-dependent increases of the noradrenaline (NA) release in the PVN (1 ng: 30.95 +/- 6.01 to 47.38 +/- 6.79 pg/sample, P less than or equal to 0.01; 100 ng: 32.93 +/- 5.38 to 73.18 +/- 11.4 pg/sample, P less than or equal to 0.01). These changes coincided in extent and duration with the respective pressor responses. A subpressor dose of ANG II (100 pg) did not release catecholamines from the PVN. Dopamine (DA) and the NA and DA, metabolites 3,4-dihydroxyphenylethylglycol and 3,4-dihydroxyphenylacetic acid, were not influenced by i.c.v. injections of ANG II at any dose. Pretreatment with the novel non-peptide ANG II-AT 1 receptor antagonist DuP 753 (5 micrograms, i.c.v.) abolished the effect of 100 ng ANG II on blood pressure and on NA release. Our results show for the first time in vivo that stimulation of periventricular ANG II-AT 1 receptors induces a selective NA release in the PVN. They further support the hypothesis that ANG II engages a noradrenergic pathway in the PVN to release vasopressin. PMID- 1611473 TI - Microinjection of arginine-vasopressin into the periaqueductal gray stimulates flank marking in Syrian hamsters (Mesocricetus auratus). AB - Syrian hamsters can communicate using a distinctive form of scent marking called flank marking. Vasopressin-sensitive neurons within the medial preoptic-anterior hypothalamic continuum (MPOA-AH) play a critical role in the control of this form of olfactory communication. Extrahypothalamic regions may also mediate hamster flank marking. Since the MPOA-AH and the periaqueductal gray (PAG) are reciprocally connected, the present study investigated whether PAG neurons are involved in the control of flank marking. The first study found that microinjection of vasopressin, but not oxytocin or saline, into the PAG induced high levels of flank marking in male (n = 8) and female (n = 5) hamsters (P less than 0.01). The second study demonstrated that microinjection of vasopressin into the PAG stimulated flank marking in a dose-dependent manner in both male (n = 7) and female (n = 11) hamsters (P less than 0.01). These data suggest that vasopressin-responsive neurons within the periaqueductal gray participate in the control of hamster flank marking. PMID- 1611475 TI - In vivo pulsatile LHRH release into the anterior pituitary of the male rat: effects of castration. AB - The effects of castration on the concentration of luteinizing hormone releasing hormone (LHRH) in the anterior pituitary (PIT) was studied in freely-behaving male rats using a push-pull cannula for sampling. In over 70 perfusions of the PIT of rats sampled before and at multiple days after castration there was no consistent change detected in the overall amount, secretory pulse amplitude or frequency or the LHRH signal reaching the PIT. PMID- 1611474 TI - Beta-amyloid stimulates glial cells in vitro to produce growth factors that accumulate in senile plaques in Alzheimer's disease. AB - The effects of a synthetic homolog of beta-amyloid (beta 1-42) on the secretion of interleukin-1 (IL-1) and basic fibroblast growth factor (bFGF) from cultures of microglia and astrocytes, cells that surround beta-amyloid-containing plaques in Alzheimer's disease, were examined. Our results show that beta-amyloid not only enhances glial cell secretion of these factors, it stimulates the proliferation and morphological transformation of microglia. Since IL-1 and bFGF are known to elevate the synthesis of the beta-amyloid precursor protein and other plaque components, it is suggested that in this way, cascades may arise that contribute to the process of plaque development. PMID- 1611476 TI - The direction of apomorphine-induced rotation behavior is dependent on the location of excitotoxin lesions in the rat basal ganglia. AB - Adult rats received unilateral kainic acid (KA) lesions of the striatum with the anterior/posterior coordinates of the lesion at either 1.5 mm or 0.3 mm anterior to bregma. Four to six weeks after the lesion rats were placed in an open field environment and injected with apomorphine (1 mg/kg, s.c.). Rats receiving the more posterior lesion (0.3 mm) rotated ipsilateral to the lesioned side of the brain. In contrast, the majority of rats receiving the more anterior (1.5 mm) placement of the lesion rotated contralateral to the lesioned side of the brain. Histological analysis of several animals receiving posterior lesions revealed damage to the hippocampus and thalamus that was not seen in the animals receiving anterior lesions. Our results are consistent with the hypothesis that the direction of apomorphine-induced rotation after excitotoxin injection into the rat basal ganglia is dependent on the location of the lesion. PMID- 1611477 TI - Decreased expression of neurotrophin-3 mRNA in the rat hippocampus following transient forebrain ischemia. AB - The expression profile of neurotrophin-3 (NT-3) mRNA in the rat hippocampus after forebrain ischemia was investigated by Northern blot and S1 nuclease protection analyses. The NT-3 transcripts in the hippocampus immediately decreased after ischemic insult, became undetectable within 3 h and remained at undetectable levels for at least 7 days. In contrast, the expression of c-fos and c-jun mRNA transiently increased both in the cerebral cortex and in the hippocampus. These results suggest that brain ischemia triggers dynamic changes in gene expression including a neurotrophic factor, which may cause functional and/or morphological changes of the neuronal network. PMID- 1611478 TI - Acute alcohol alters the excitability of cerebellar Purkinje neurons and hippocampal neurons in culture. AB - Acute exposure to ethanol at 22 and 44 mM concentrations altered several features of the current-evoked voltage responses of cerebellar Purkinje neurons and hippocampal neurons studied in culture model systems. Whole cell current clamp techniques were used. At 22 mM, ethanol depressed current-evoked spiking in the hippocampal neurons but enhanced the current-evoked spiking in the Purkinje neurons. In both neuronal types, 44 mM ethanol depressed spiking, the amplitude of the afterhyperpolarization generated at the termination of a current pulse and the amplitude of the off-response generated at the termination of a hyperpolarizing pulse. Ethanol had little or no effect on resting membrane potential or the passive membrane properties measured near resting level in either neuronal type. Some changes in the current-voltage curves were observed at more depolarized or hyperpolarized potentials in both neuronal types. In the Purkinje neurons, where spontaneous activity was a prominent feature of some recordings, exposure to ethanol reduced the frequency of the spontaneous events. These results indicate that acute exposure to ethanol at intoxicating doses alters the membrane excitability of these two CNS neuronal types. The ethanol induced changes in neuronal excitability presumably contribute to the changes in firing properties observed in extracellular recordings from these neuronal types in vivo and the behavioral effects observed during alcohol intoxication in animal models. PMID- 1611479 TI - Distribution of immunoreactive T-kininogen in rat nervous tissues. AB - The distribution in the nervous system of T-kininogen, the third kallikrein resistant kininogen of the rat, was determined using bioassays and a radioimmunoassay system. In rat brain homogenates, trypsin released large amounts of a kinin-like myostimulating activity while urinary kallikrein released small amounts. The kinins released by trypsin were identified by HPLC as mostly T kinin. Radioimmunoassays showed that a T-kininogen-like immunoreactive factor was uniformly distributed throughout the central nervous system. Higher levels were found in female rats than in male rats. Maximum levels were observed in newborn animals. A slight increase of T-kininogen content of the brain was observed after turpentine injection while T-kininogen level in liver was dramatically increased. T-kininogen plasma contamination to the nervous tissues was estimated by injecting 125I-labelled T-kininogen. The T-kininogen content of rat cultured cells and neurons was also examined. Highest levels were found in dorsal root ganglia neurons, lower levels in Schwann cells, phaeochromocytoma cells, mixed cells from spinal ganglion and in astrocytes. Immunocytochemistry showed the presence of T-kininogen in the cytoplasm of cultured dorsal root ganglia neurons and embryonic hippocampal neurons. The distribution of T-kininogen throughout the central and peripheral nervous system of the rat, the variations of its level during the life span suggest that T-kininogen would play the role of a cysteine proteinase inhibitor and not that of a T-kinin-releasing substrate in nervous tissues. PMID- 1611480 TI - Effect of MK-801 on the induction and subsequent decay of long-term potentiation in the unanesthetized rabbit hippocampal dentate gyrus. AB - Several investigations have shown that the N-methyl-D-aspartate (NMDA) antagonist MK-801 interferes both with learning and a candidate neural mechanism for learning, the long-term potentiation (LTP) phenomenon. The low doses of MK-801 reported to block learning, however, may not be sufficient to block LTP. The present experiments examined the effects of 4 doses (0.05, 0.10, 0.50 and 1.00 mg/kg) of MK-801 on LTP of the perforant path-granule cell population excitatory postsynaptic potential (EPSP) and spike in unanesthetized rabbits. MK-801 did not significantly affect the threshold intensity for LTP of the population EPSP but the 3 highest doses did increase the threshold for LTP of the population spike. The 3 highest doses also reduced the peak magnitude and the duration of LTP of the spike to less than 24 h. The 0.05 m/kg dose did not affect the threshold or peak magnitude of spike LTP, but did decrease the decay time constant to 10.4 days, compared to 20.8 days in control rabbits. Only the 1.00 mg/kg dose reduced the magnitude of LTP of the EPSP. It was not possible to determine if MK-801 altered the longer-lasting component of LTP of the EPSP as it never persisted for longer than 24 h. These studies demonstrate that MK-801 disrupts LTP at doses also known to interfere with learning. PMID- 1611482 TI - Glycine-like immunoreactive input to sympathetic preganglionic neurons. AB - The organization of glycine-like immunoreactive (GLY-LIR) processes was investigated within the sympathetic preganglionic neuropils of male Sprague Dawley rats and pigeons (Columba livia). Sympathetic preganglionic neurons were retrogradely labeled with horseradish peroxidase following injections into the superior cervical ganglion in rats or into the avian homologue of the mammalian stellate ganglion (paravertebral ganglion 14) in pigeons. Glycine-like immunoreactivity was visualized using postembedding immunoperoxidase and immunogold labeling methods. The neuropils surrounding pigeon sympathetic preganglionic neurons in the principal preganglionic cell column (nucleus of Terni) and in the nucleus intercalatus contained numerous GLY-LIR puncta. Many of these processes appeared to be 'terminal-like' swellings which closely apposed retrogradely labeled preganglionic perikarya and proximal dendrites. GLY-LIR somal and dendritic processes were intermingled among retrogradely labeled preganglionic neurons in the nucleus of Terni. None of these GLY-LIR cells were retrogradely labeled. The neuropils surrounding sympathetic preganglionic neurons in the rat also contained numerous GLY-LIR puncta; there were, however, qualitative differences in the density of such profiles across the preganglionic subnuclei. Within the central autonomic and intercalated regions there were numerous GLY-LIR processes, many of which closely apposed retrogradely labeled sympathetic preganglionic somas and proximal dendrites. Within the principal preganglionic cell column, the nucleus intermediolateralis pars principalis (Ilp), there were very few GLY-LIR 'terminal-like' swellings closely apposed to cell bodies in regions of high somal packing density. In regions were this density diminished, GLY-LIR puncta closely apposed retrogradely labeled perikarya and proximal dendritic processes. GLY-LIR spinal neurons were never observed to be within Ilp proper but were present in areas immediately dorsal (lateral lamina V), medial and ventral (lateral lamina VII). GLY-LIR neurons were never retrogradely labeled. The ultrastructural features of GLY-LIR terminals within the sympathetic preganglionic neuropils of both vertebrates were nearly identical. GLY-LIR terminal boutons formed synaptic contacts with retrogradely labeled preganglionic somas as well as with large and medium-sized proximal dendrites. The majority of identified GLY-LIR terminals, however, contacted non retrogradely labeled medium and small caliber dendrites within the preganglionic neuropils. Ninety-eight percent of GLY-LIR synapses formed symmetric specializations with the postsynaptic element. Ninety-six percent of the GLY-LIR terminal boutons contained some combination of pleomorphic vesicles. These light and electron microscopic observations support the hypothesis that glycine is localized in terminals presynaptic to sympathetic preganglionic perikarya and dendrites.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611481 TI - Hypothalamic osmoregulation for vasopressin release in streptozotocin-diabetic rats in vivo and in vitro. AB - The central osmoregulation mechanism for vasopressin (VP) release was studied in the streptozotocin diabetic (STZ-DM) rat. Electrical activities of the VP producing cell in the supraoptic nucleus (SON) were recorded extracellularly and compared with those in the control rat both in vivo and in vitro. Neuronal activities in the periventricular area (PVA) were also recorded in the in vitro experiment. Hyperosmolar stimulation which was done with an intraperitoneal injection of 1.0 M NaCl (4 ml/kg) resulted in an increase in plasma osmolality both of STZ-DM (increased by 14 +/- 2 mOsml/kg H2O) and control rats (15 +/- 3 mOsmol/kg H2O). Increased plasma osmolality caused significant increase in the mean discharge rate of VP-producing cells in the control animals, but only an insignificant change in STZ-DM rats. In the hypothalamic slice preparations incubated in the artificial cerebrospinal fluid (301 +/- 2 mOsml/kg H2O), VP producing cells in control rats increased their discharge rate linearly as the osmolality (310 +/- 2 and 320 +/- 1 mOsmol/kg H2O) or concentration (10(-8) and 10(-6) M) of angiotensin II (AGII) of the perfusate was increased stepwise, but there was no change in response to either stimulus in STZ-DM rats. On the other hand, there was no difference in sensitivity to osmolality and AGII of PVA neurons in both animal groups. These data indicate that lower sensibility to osmotic change of VP-producing cells in STZ-DM rats may depend, at least partially, upon the disturbance of osmo- and AGII-sensitivity in VP-producing cells themselves, and that these changes seem to be restricted to SON VP producing cells. PMID- 1611483 TI - Taurine and glycine activate the same Cl- conductance in substantia nigra dopamine neurones. AB - Intracellular recordings were made from substantia nigra dopamine neurones in a rat brain slice preparation. Spontaneous firing in these cells was reversibly inhibited by taurine applied by superfusion (300 microM-20 mM) or by focal pressure ejection. Neurones recorded with electrodes filled with KCl were depolarised at resting potential by taurine; the taurine depolarisation reversed polarity at -36.6 +/- 1.0 mV (7 cells). When electrodes filled with K-acetate or K-methyl sulphate were used, taurine caused a hyperpolarisation which reversed at -74.2 +/- 3.8 mV (9 cells). These effects of taurine were accompanied by a fall in input resistance or, in voltage clamp, an increase in conductance. Taurine thus appeared to increase membrane chloride conductance. The effect of taurine persisted in tetrodotoxin, 0-Ca2+/10 mM Mg2+, and bicuculline, but was blocked by strychnine (10 microM). Maximal responses to either taurine or glycine occluded responses to the other amino acid. Taurine therefore acts directly on dopamine neurones in the substantia nigra to increase the same membrane Cl- conductance as that mediating the action of glycine. Taurine may also act at the same recognition site as glycine in these cells. PMID- 1611484 TI - Regional distribution of histamine in the brain of non-mammalian vertebrates. AB - The histamine contents in the brains of various species of non-mammalian vertebrates were determined by an HPLC-fluorometric method. The whole brain contents of histamine in birds (200-500 pmoles/g) were comparable to those in mammals, but were higher in reptiles (1000-13500 pmoles/g) and amphibia (1600 2200 pmoles/g) and lower in teleosts (10-50 pmoles/g). In all species, histamine was unevenly distributed, being present at highest concentrations in the diencephalon, except in teleosts, in which its content was highest in the telencephalon. The brain histamine contents were proportional to the reported densities of histamine-immunoreactive fibers. PMID- 1611485 TI - Spectrum of amyloid beta-protein immunoreactivity in hereditary Alzheimer disease with a guanine to thymine missense change at position 1924 of the APP gene. AB - We studied neuropathologically 3 patients of a previously unreported kindred of presenile Alzheimer disease (AD), characterized by a G to T mutation at base pair 1924 (695 transcript) of the amyloid precursor protein gene. Classic features of presenile AD are observed. Neurofibrillary tangles with paired helical filaments as well as neuritic plaques are found in large number in neocortex and hippocampus. beta-Protein deposits in meningeal and parenchymal vessels are present, but not severe. Prominent subpial ribbon-like deposits are detected with antibodies to a 28-residue synthetic peptide; however, only occasionally can they be seen in thioflavin S treated sections. Along with a mild involvement of vessels, as demonstrated by beta-protein immunolabeling, parenchymal involvement is also seen in the cerebellar molecular layer. In the course of the study, we have not detected neuropathologic changes, which are mutation specific. Further investigations of familial Alzheimer disease with known genetic mutations will clarify whether correlations exist between specific mutations and neuropathologic phenotypes. PMID- 1611486 TI - Effects of lesions of locus coeruleus/subcoeruleus on diffuse noxious inhibitory controls in the rat. AB - Diffuse noxious inhibitory controls (DNIC) acting on trigeminal convergent neurons were compared in sham-operated animals and rats with quinolinic acid induced lesions of the locus coeruleus/subcoeruleus (LC/SC). No significant differences were observed between control animals and those with ipsilateral, contralateral or bilateral lesions of the LC/SC, in respect of: (1) the general properties of the recorded units; and (2) the magnitude of the depressions of C fiber-evoked responses of convergent neurons produced by immersing each paw in a 50 degrees C water bath (i.e. DNIC). It is concluded that the LC/SC is not involved, at least directly, in the supraspinal part of the loop which subserves DNIC in the rat. PMID- 1611487 TI - The excitotoxicity of heterocyclic dicarboxylic acids in rat hippocampal slices: structure-activity relationships. AB - The structural resemblance of certain heterocyclic dicarboxylates to aspartate and glutamate led investigators to study their potency as agonists and antagonists of the N-methyl-D-aspartate (NMDA) receptor. The sensitivity of hypoxic rat hippocampal slices to NMDA ligands is several fold greater than that of normoxic slices. In the present study, the excitotoxic potency of heterocyclic dicarboxylates was assessed electrophysiologically by measuring their ability to enhance hypoxic and hypoglycemic neuronal damage in the rat hippocampal slice preparation. Four compounds were tested: quinolinate (QUIN), 4,5-imidazole dicarboxylate (IZDA), 1,2,3-triazole-4,5-dicarboxylate (TZDA), and 2,3 pyrazinedicarboxylate (PZDA). QUIN was the most toxic drug in enhancing both hypoxic and hypoglycemic neuronal damage. IZDA and TZDA were slightly less toxic than QUIN, while PZDA was innocuous. The effect of the 3 active drugs was blocked by the NMDA competitive antagonist DL-2-amino-5-phosphonovalerate. The sequence N-CH(COOH)-CH(COOH)- appears to be a prerequisite for a heterocyclic dicarboxylate to exert NMDA-type agonistic properties. A 5-membered ring heterocyclic compound which contains more than one nitrogen atom in its ring retains its NMDA-type toxicity while a 6-membered ring with more than one nitrogen atom (PZDA) does not. PMID- 1611488 TI - Cerebral glucose utilization during stage 2 sleep in man. AB - Using [18F]fluorodeoxyglucose method and positron emission tomography, we performed paired determinations of the cerebral glucose utilization at one week intervals during sleep and wakefulness, in 12 young normal subjects. During 6 of 28 sleep runs, a stable stage 2 SWS was observed that fulfilled the steady-state conditions of the model. The cerebral glucose utilization during stage 2 SWS was lower than during wakefulness, but the variation did not significantly differ from zero (mean variation: -11.5 +/- 25.57%, P = 0.28). The analysis of 89 regions of interest showed that glucose metabolism differed significantly from that observed at wake in 6 brain regions, among them both thalamic nuclei. We conclude that the brain energy metabolism is not homogeneous throughout all the stages of non-REMS but decreases from stage 2 SWS to deep SWS; we suggest that a low thalamic glucose metabolism is a metabolic feature common to both stage 2 and deep SWS, reflecting the inhibitory processes observed in the thalamus during these stages of sleep. Stage 2 SWS might protect the stability of sleep by insulating the subject from the environment and might be a prerequisite to the full development of other phases of sleep, especially deep SWS. PMID- 1611489 TI - A muscarinic receptor agonist mobilizes Ca2+ from caffeine and inositol-1,4,5 trisphosphate-sensitive Ca2+ stores in cat adrenal chromaffin cells. AB - To gain some understanding of the characteristics of intracellular Ca2+ stores of cat adrenal chromaffin cells, we investigated the effects of ryanodine, a blocker of Ca(2+)-induced Ca2+ release channels in muscle, on both cytosolic Ca2+ concentration and catecholamine secretion induced by caffeine or methacholine. The results suggest that Ca2+ stores consist of at least two compartments, one which is sensitive to both caffeine and inositol-1,4,5-trisphosphate (IP3), and the other which is sensitive to IP3 alone. PMID- 1611490 TI - Activity of the conformationally rigid 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS)-1-amino-3-(phosphonomethylene)cyclobutane-1-carboxylic acid (cyclobutylene AP5) on evoked responses in the perforant pathway of rat hippocampus. AB - The highly rigid and conformationally extended 2-amino-4-phosphonobutanoic acid (AP4) analogue (RS)-1-amino-3-(phosphonomethylene)-cyclobutane-1-carboxylic acid (cyclobutylene AP5) was synthesized and found to inhibit evoked responses in the rat lateral perforant path (LPP) with an IC50 of 41 (+/- 1.5 S.E.M.) microM and the medial perforant pathway with an IC50 of 218 (+/- 3.7 S.E.M.) microM. Furthermore, paired pulse potentiation experiments suggest that cyclobutylene AP5 acts, in part, at a presynaptic site in the LPP. Thus, cyclobutylene AP5 appears to act in a similar manner to L-AP4 in the perforant pathway. These data support the hypothesis that L-AP4 assumes an extended conformation at the L-AP4 receptor of the LPP. PMID- 1611491 TI - A CNS specific proteoglycan associated with astrocytes in rat optic nerve. AB - A novel CNS specific keratan sulfate proteoglycan is identified by a monoclonal antibody (mAb) TED15. The antibody recognizes a carbohydrate epitope that is removed from the core protein following keratanase digestion. The relative molecular weight of the glycoprotein is not altered following digestion with heparinase, heparitinase or chondroitinase ABC. By immunoblot analysis, the TED15 antigen is differentially distributed in diencephalic derivatives, being present in the optic nerve but absent from the retina. Within the optic nerve, the TED15 antigen is associated with astrocytes, while in the retina no labeling of astrocytes of Muller cells is observed. PMID- 1611492 TI - Effects of selective CCK receptor agonists on food intake after central or peripheral administration in rats. AB - In this paper report the effects of peripheral (intraperitoneal, i.p.) and central (intracerebroventricular, i.c.v.) injection of selective cholecystokinin (CCK) receptor agonists on food intake in the rat. Stimulation of peripheral and central CCK-A receptors by the selective CCK-A receptor agonist A-71623 suppressed intakes of a liquid diet in both deprived and sated rats. In contrast, i.c.v., but not i.p., injections of the selective CCK-B receptor agonist A-63387, reduced food intakes, although on a molar basis the effect was much less than that seen with A-71623. Although these results stress the relative importance of the CCK-A receptor in the effects of exogenous CCK-8 administration on feeding, stimulation of the CCK-B receptor may still be involved in the control of feeding following the endogenous release of CCK. PMID- 1611493 TI - Responses of neurons in ventroposterolateral nucleus of primate thalamus to urinary bladder distension. AB - The purpose of this study was to examine effects of a noxious visceral stimulus, urinary bladder distension (UBD), on cells in the ventroposterolateral (VPL) nucleus of anesthetized monkeys. We hypothesized that processing of visceral information in the VPL nucleus of the thalamus is similar to spinothalamic tract (STT) organization of visceral afferent input. Urinary bladder distension excites sacral and upper-lumbar STT cells that have somatic input from proximal somatic fields; whereas, thoracic STT cells are inhibited by UBD. Extracellular action potentials of 67 neurons were recorded in VPL nucleus. Urinary bladder distension excited 22 cells, inhibited 9 cells, and did not affect activity of 36 cells. Seventeen of 22 cells excited by UBD also received convergent somatic input from noxious squeeze of the hip, groin, or perineal regions. No cells activated only by innocuous somatic stimuli were excited by UBD. Five of 9 cells inhibited by UBD had upper-body somatic fields. There was a significant tendency for VPL neurons excited by UBD to have proximal lower-body somatic fields that were excited by noxious stimulation of skin and underlying muscle (P less than 0.001). Antidromic activation of 4 thalamic neurons affected by UBD showed that visceral input stimulated by UBD reached the primary somatosensory (SI) cortex. PMID- 1611494 TI - Pontine regulation of REM sleep components in cats: integrity of the pedunculopontine tegmentum (PPT) is important for phasic events but unnecessary for atonia during REM sleep. AB - Transection, lesion and unit recording studies have localized rapid eye movement (REM) sleep mechanisms to the pons. Recent work has emphasized the role of pontine cholinergic cells, especially those of the pedunculopontine tegmentum (PPT). The present study differentiated REM sleep deficits associated with lesions of the PPT from other pontine regions implicated in REM sleep generation, including those with predominantly cholinergic vs non-cholinergic cells. Twelve hour polygraphic recordings were obtained in 18 cats before and 1-2 weeks after bilateral electrolytic or radio frequency lesions of either: (1) PPT, which contains the dorsolateral pontine cholinergic cell column; (2) laterodorsal tegmental nucleus (LDT), which contains the dorsomedial pontine cholinergic cell column; (3) locus ceruleus (LC), which contains mostly noradrenergic cells; or (4) subceruleus (LC alpha, peri-LC alpha and the lateral tegmental field), which also contains predominantly noncholinergic cells. There were three main findings: (i) Only lesions of PPT and subceruleus significantly affected REM sleep time. These lesions produced comparable reductions in REM sleep time but influenced REM sleep components quite differently: (ii) PPT lesions, estimated to damage 90 +/- 4% of cholinergic cells, reduced the number of REM sleep entrances and phasic events, including ponto-geniculooccipital (PGO) spikes and rapid eye movements (REMs), but did not prevent complete atonia during REM sleep: (iii) Subceruleus lesions eliminated atonia during REM sleep. Mobility appeared to arouse the cat prematurely from REM sleep and may explain the brief duration of REM sleep epochs seen exclusively in this group. Despite the reduced amount of REM sleep, the total number of PGO spikes and REM sleep entrances increased over baseline values. Collectively, the results distinguish pontine loci regulating phasic events vs atonia. PPT lesions reduced phasic events, whereas subceruleus lesions created REM sleep without atonia. Severe REM sleep deficits after large pontine lesions, including PPT and subceruleus, might be explained by simultaneous production of both REM sleep syndromes. However, extensive loss of ACh neurons in the PPT does not disrupt REM sleep atonia. PMID- 1611495 TI - Fenfluramine-induced increases in extracellular hippocampal serotonin are progressively attenuated in vivo during a four-day fenfluramine regimen in rats. AB - Rats were administered 8 injections of 12.5 mg/kg fenfluramine over a 4-day period. Extracellular hippocampal serotonin levels were monitored in vivo during the 4-day treatment period. Predrug baseline serotonin levels were 0.6 +/- 0.17 pg/5 microliters; 60 min after the first fenfluramine injection extracellular serotonin levels were increased to 28.06 +/- 5.2 pg/5 microliters. Fenfluramine induced increases in serotonin were substantially reduced on the 2nd through 4th days of the regimen. Baseline serotonin levels were increased on days 2 through 4 of the treatment regimen. In a separate group of animals post-mortem tissue concentrations of serotonin were measured 2 weeks after 1,2,4, or 8 injections of 12.5 mg/kg fenfluramine. There were decreases in serotonin tissue concentrations which were related to the number of fenfluramine injections administered. The in vivo dialysis and post-mortem tissue assay results are consistent with the view that fenfluramine is neurotoxic. PMID- 1611496 TI - Effects of castration on LH-RH patterns in intrahypophysial microdialysates. AB - A microdialysis system was used to monitor LH-RH patterns in the extracellular fluid of the adenohypophysis of testes-intact and short-term castrate rats. Male rats received guide cannulae implants fitted with stylets that extended into the anterior pole of the anterior pituitary gland. At the same time, animals were either castrated or received sham surgeries. On day 4 following surgeries, microdialysis probes were inserted into the guide cannulae and artificial CSF was pumped through the system at a flow rate of 2.5 microliters/min. Continuous samples were obtained from each animal over 5- or 10-min intervals throughout 4-7 sessions. Placements of probe tips were verified by histological examination of stained tissue sections. In vitro tests of microdialysis probe performance revealed an exchange rate of 4% at the 2.5 microliters/min flow rate. In vivo patterns of LH-RH in microdialysates obtained from sham-operated and castrate rats were pulsatile, as determined by the computer algorithm ULTRA. Pulses of LH RH occurred at a higher frequency (P less than 0.05) in the castrates (1.30 +/- 0.26 pulses/h, n = 6) versus the sham-castrates (0.87 +/- 0.06 pulses/h, n = 11). Mean LH-RH pulse amplitude (castrates delta 0.24 +/- 0.03 pg, testes-intact delta 0.42 +/- 0.06 pg) and mean LH-RH levels (castrate 0.37 +/- 0.04 pg/10 min, intact 0.48 +/- 0.06 pg/10 min), however, were not significantly changed by castration (delta = difference between trough and peak LH-RH value of an LH-RH pulse).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611498 TI - Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat. AB - We have previously demonstrated that oxypurinol (40 mg/kg i.p.), a xanthine oxidase inhibitor, can reduce focal ischemic brain injury in the rat when applied pre-ischemically. By using a model of occlusion of the middle cerebral artery (MCA) in tandem with occlusion of the ipsilateral carotid artery, the present study further demonstrates that delayed (60 min) administration of oxypurinol also exhibits a protective action on ischemic damage in the stroked rat brain. Oxypurinol significantly reduced the ischemic cerebral infarct zone by preventing the development of brain damage primarily in areas distant to the central lesion core. A corresponding amelioration of brain swelling and attenuation of neurological deficits were evident. Similar protection against focal ischemic brain damage was evident when the adenosine deaminase inhibitor, deoxycoformycin (500 micrograms/kg), was administered prior to the onset of ischemia. However, with delayed (60 min) administration deoxycoformycin had no protective effect. These findings support the hypothesis that manipulation of adenosine catabolism can be an effective therapeutic approach to the prevention or treatment of brain injuries, such as those occurring during ischemic stroke or cardiac arrest. PMID- 1611497 TI - Effects of acute and chronic clozapine on dopaminergic function in medial prefrontal cortex of awake, freely moving rats. AB - We previously showed that chronic administration of the clinically atypical and clinically superior antipsychotic drug clozapine selectively reduces dopamine (DA) release in the nucleus accumbens but not neostriatum, and that this effect appears mediated by anatomically selective mesolimbic DA depolarization blockade. The present study extends that research to another mesocorticolimbic DA locus, the medial prefrontal cortex. Acute clozapine challenge (5-40 mg/kg i.p.) produced dose-dependent increased extracellular levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the medial prefrontal cortex of awake, free-moving rats as measured by in vivo brain microdialysis. Chronic clozapine treatment (20 mg/kg/day for 21 days) did not significantly change basal extracellular levels of DA, DOPAC or HVA. Acute clozapine challenge on day 22 in the chronic clozapine-treated animals produced no significant differences in medial prefrontal cortex DA, DOPAC or HVA as compared to chronic vehicle-treated animals, indicating that tolerance to clozapine does not develop in the mesocortical DA system, in contrast to the mesolimbic system. The DA agonist apomorphine (100 micrograms/kg) produced decreased basal extracellular levels of DA, DOPAC and HVA in medial prefrontal cortex of both chronic clozapine-treated and chronic vehicle-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611499 TI - Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal. AB - The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Botzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during sniffing reflex is worthy of further note in that, based on power spectrum analyses of concurrently recorded ECoG activities, this particular discharge pattern was clearly associated with the activation of a 6-10 Hz theta rhythm. These findings indicated that bulbar RRU activity patterns are subject to change by not only behaviors and sleep/wakefulness cycles, but also a variety of modulatory influences and feedback/feedforward biases from other central and peripheral physiological control mechanisms. PMID- 1611500 TI - The neurotoxic actions of ibotenic acid on cholinergic and opioid peptidergic systems in the central nervous system of the rat. AB - The neurotoxic effects produced by ibotenic acid (IA) induced chemical lesions of the central nervous system (CNS) cholinergic system were examined on the opioid peptidergic system in adult rats. Forebrain cholinergic systems were bilaterally lesioned by the infusion of IA (1 or 5 micrograms/site) into the nucleus basalis magnocellularis (NBM). One week after the injections, the animals were sacrificed, and activities of acetylcholinesterase (AChE), choline acetyltransferase (ChAT) and concentrations of beta-endorphin (beta-End) and Met enkephalin (Met-Enk) were measured in different brain regions. Animals treated with IA showed a decrease in the activity of ChAT (-24%), AChE (-36%) and beta End level (-33%) in the frontoparietal cortex (FC). For the first time we report that these changes were associated with a compensatory increase in the activity of ChAT (+27%), AChE (+25%), beta-End level (+66%) in the remaining part of the cortex, i.e. cortex devoid of frontal cortex (C-FC). Met-enkephalin level increased by 59% in the frontoparietal cortex and did not change in the cortex devoid of frontal cortex upon IA treatment. These results suggest that IA treatment results in changes in the activity of cortical ChAT and AChE, and beta End level in the same direction. Injection of IA in the NBM did not cause a change in the activity of ChAT or AChE in other brain regions such as hippocampus, striatum or midbrain. In addition to cortex devoid of frontal cortex, midbrain also showed a significant increase in the beta-End level in the IA treated animals. However, pituitary beta-End decreased in the neurotoxin treated animals.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611501 TI - Behavior, ectopias and immunity in BD/DB reciprocal crosses. AB - In a previous study, in which fertilized DBA ova were transferred into an autoimmune female, and NZB ova were transferred into a non-autoimmune female, we found that (1) the maternal environment affected the degree of autoimmunity, (2) the incidence of cortical ectopias was not affected by the maternal environment (3) DBA and NZB females had greater paw asymmetry if reared in an autoimmune uterus, and (4) avoidance learning scores were inversely related to degree of autoimmunity. In the present experiment, reciprocal crosses of DBA and BXSB mice were studied to confirm and extend the original findings. DB mice (DBA female x BXSB male) had greater immune activity than the BD animals, had poorer avoidance learning, but were better on black-white discrimination learning and the Lashley III maze. The BD mice had greater paw asymmetry. Only one of 38 animals had a cortical ectopia. The results lead to the following conclusions: (1) there is an inverse relationship between amount of immune activity and active avoidance learning; (2) some uterine factor in autoimmune mice causes females to have greater paw asymmetry; (3) cortical ectopias are under genetic control; and (4) the lesser immune activity of the BD mice suggests that they developed a suppressor system following early exposure to autoimmunity in the uterine/maternal environment. PMID- 1611502 TI - Golgi-like staining of visual cortex cells obtained by extracellular biocytin application in vitro. AB - We report here the application of biocytin (a biotin-lysine complex) as an extracellular tracer in vitro. Biocytin was applied extracellularly, revealing Golgi-like staining of cells in the adult in vitro rat visual cortex. Micropipettes were filled with a solution of 2.3-2.6% biocytin dissolved in 0.05 M Tris buffer, pH 7.4. Biocytin was applied by one of 3 methods: diffusion, pressure injection or drop application. Cell bodies and dendrites around the application site and their efferent axonal processes were stained; dendritic spines were often visible. The injection sites varied in size from a single cell to a diameter of 400 microns. When applied in layer I-III, few filled cells were also seen in layers IV and V, outside the application site. The drop application (5-10 microliters) of biocytin resulted in filling of cells throughout the cortex. The combination of biocytin and the slice preparation was found to be very useful in revealing cell morphology and tracing interlaminar connections in the visual cortex. The advantages of this technique are its ease of application, the precise and restricted injection sites, and Golgi-like morphological detail. PMID- 1611503 TI - Serotonin reduces a voltage-dependent transient outward potassium current and enhances excitability of cerebellar Purkinje cells. AB - Utilizing current-clamp and single electrode voltage-clamp techniques we have studied the actions of serotonin (5-HT) on a transient outward voltage-dependent potassium current in adult rat Purkinje cells (PCs) in vitro. Under voltage clamp, bath-applied 5-HT (10 nM-100 microM) reversibly depressed a transient outward potassium current in a dose-dependent manner in 24 of 26 neurons. This depression was apparent at all test command voltages. In current clamp, with normal bathing medium, 5-HT decreased the latency to first spike firing and increased the number of spikes in response to depolarization. Similar effects were evident when 4-aminopyridine was applied. In bathing medium containing TTX, Cs+ and Ni2+ to block voltage-activated currents, 5-HT increased the trajectory of the electrotonic membrane response elicited by depolarizing current injection. Enhanced responsiveness of PCs by 5-HT was not related to changes in membrane potential or input resistance. These experiments indicate that one mechanism by which 5-HT can increase the excitability of PCs is via reduction of a transient outward current. PMID- 1611504 TI - Characterization of a putatively vesicular binding site for [3H]MPP+ in mouse striatal membranes. AB - [3H] N-Methyl-4-phenylpyridinium ion (MPP+) binds with a fully reversible, high affinity process to a population of sites mainly localized in the mouse striatum (Bmax = 168 +/- 15 fmol/mg protein, KD = 1.4 +/- 0.4 nM). The majority of specifically-bound radioactivity was localized in the synaptosomal fraction. Unilateral, striatal denervation with 6-hydroxydopamine (6-OHDA) markedly (by 65 70%) decreased the number of [3H]MPP+ sites. Besides dopamine, the vesicular markers tyramine, tetrabenazine and reserpine inhibited [3H]MPP+, while mazindol was a poor displacer. Adenosine triphosphate (ATP) and Mg(2+)-ions did not affect [3H]MPP+ binding. It is concluded that these sites may represent a marker of striatal storage vesicles for dopamine. PMID- 1611505 TI - Abnormally high activity of 3-hydroxyanthranilate 3,4-dioxygenase in brain of epilepsy-prone El mice. AB - Quinolinic acid (QUI), a structural analogue of neurotransmitters such as L glutamate and L-aspartate, may act as an 'excitotoxin' when it is abundant in the brain. The compound has been causally related to various neurodegenerative disorders, including epilepsy. We tested the capacity of the brains of epilepsy prone El mice to synthesize QUI. The activity of 3-hydroxyanthranilate 3,4 dioxygenase in the cerebral cortex of El mice was about 17 times that of ddY mice, the parent strain of El mice. The activity of this enzyme was undetectable in brains of BALB/cA mice and C3H/HeN mice. In El mice the sexes had comparable enzyme activity. The enzyme activity increased gradually as the animals aged. An injection of endotoxin caused a further increase in the enzyme activity. The enzyme activity in the spleen of El mice did not differ from that of ddY mice, and endotoxin did not affect the enzyme activity in the spleen. No strain difference was observed in the activity of quinolinate phosphoribosyltransferase, a QUI-degrading enzyme, in the cerebral cortex. These results suggest that an increase in the synthesis of QUI in the brain is involved in the pathogenesis of epileptic seizures in El mice. PMID- 1611506 TI - The central organization of carotid body afferent projections to the brainstem of the rat. AB - Despite increasing focus on brainstem respiratory control mechanisms in the rat, relatively little is known about the central organization of chemoreceptor pathways in this species. To approach this issue, the present study sought to selectively define the central projections of primary sensory neurons that innervate the carotid body. Afferent projections were visualized by horseradish peroxidase histochemistry following microinjection of wheat germ agglutinin horseradish peroxidase into the vascularly isolated carotid body in situ. Labeled afferent fibers were found in several discrete regions of the dorsomedial and ventrolateral medulla. Heaviest labeling was seen bilaterally in the commissural and medial subnuclei of the caudal nucleus tractus solitarius (nTS); more moderate labeling was found bilaterally in the intermediate, interstitial, and dorsolateral subnuclei and ipsilaterally in the ventrolateral subnuclei. In addition, we observed a prominent projection to the caudal ventrolateral medulla in the region of the nucleus retroambigualis. Sparse labeling was also seen in the dorsal motor nucleus of the vagus nerve and the area postrema. These findings support the existence of multiple pathways by which peripheral chemoreceptor inputs may influence central respiratory neurons. In addition to the classically defined relay in nTS, carotid body afferents may also interact more directly with respiratory- or cardiovascular-related neurons in other regions such as the ventrolateral medulla. PMID- 1611507 TI - Release of neurite outgrowth promoting factors by Helisoma central ganglia depends on neural activity. AB - Identified buccal neurons B5 and B19 from the mollusc, Helisoma trivolvis, were plated into cell culture in order to assay for neurite outgrowth promoting factors released from central ring ganglia. The release and attachment of neurite promoting factors to the substratum of poly-lysine coated dishes could be inhibited by blocking spontaneous bioelectric activity in central ring ganglia used to condition the medium and dishes. Bioelectric activity within neurons in central ring ganglia was assayed by intracellular recording and found to be inhibited by exposure to the sodium channel blocker, tetrodotoxin (TTX; 2 x 10( 5) M), or CoCl2 (10 mM). Neither of these agents appeared to be toxic over a three day period since activity within neurons in central ring ganglia was restored following superfusion with saline. To examine the effect of blocking neural activity on the ability of central ring ganglia to release neurite outgrowth promoting factors, we compared the percentage of neurons that extended processes under 5 different conditions: (1) dishes containing conditioned medium and substrate attached growth factors (Super SAM); (2) dishes with substrate attached growth factors only and defined medium (SAM); (3) dishes containing substrate attached growth factors prepared in the presence of TTX; or (4) CoCl2; and (5) dishes containing unconditioned defined medium. The percentage of neurons extending processes under the 5 conditions were: (1) 71% (n = 32); (2) 51% (n = 33); (3) 14% (n = 37); (4) 15% (n = 47); (5) 0% (n = 40), respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611508 TI - Growth cones of regenerating adult sciatic sensory axons release axonally transported proteins. AB - Labelled, rapidly transported axonal proteins were shown to be released from adult frog sciatic sensory neurons, regenerating in vitro after a crush injury. The spatial distribution of the transported, released proteins could accurately be resolved by culturing the nerve on nitrocellulose paper, which trapped the released proteins. The release was located to the crush and to the entire outgrowth region. When regeneration was inhibited by adenosine, the release was limited to the crush site, implying that the release was linked to the growing axons. Other experiments suggested that the release emanated from growth cones. Furthermore, two-dimensional electrophoretical analysis of both fast axonally transported and of released proteins showed that the latter represented a selection of the transported protein species. PMID- 1611509 TI - Morphine-induced increases of extracellular histamine levels in the periaqueductal grey in vivo: a microdialysis study. AB - The effect of morphine on extracellular histamine levels in two regions of the rat midbrain was studied in vivo by microdialysis. Morphine (5.6 and 12.8 mg/kg, s.c.) significantly and dose-dependently increased extracellular histamine levels in the periaqueductal grey, while no significant effect was observed in the reticular formation. In addition, no significant effect of sequential saline injections was observed on extracellular histamine levels in the periaqueductal grey. Since morphine has no effect on histamine catabolism, these results suggest that morphine increases histamine release in the rat PAG, a site where morphine and histamine are known to have analgesic action. Taken with earlier studies showing the ability of H2 antagonists to block morphine analgesia, these results support the hypothesis that histamine and H2 receptors are important in mediating morphine analgesia in the rat periaqueductal grey. The cellular origin of the extracellular histamine, and the mechanism of this morphine effect remain to be determined. PMID- 1611510 TI - Purification and structural analysis of hippocampal cholinergic neurostimulating peptide. AB - Hippocampal soluble fraction stimulates acetylcholine (AcCho) synthesis of medial septal nuclei in explant culture system. This stimulating activity was purified from 10-12-day-old rat hippocampus. During purification, the activity was separated into two fractions and a previously unreported peptide was purified from one fraction. The structure of this novel peptide is acetyl-Ala-Ala-Asp-Ile Ser-Gln-Trp-Ala-Gly-Pro-Leu and we designated it as hippocampal cholinergic neurostimulating peptide (HCNP). Synthesized HCNP and de-acetylated HCNP (free HCNP) stimulated AcCho synthesis of medial septal nuclei culture, in a dose dependent manner, but not cultures of corpus striatum or anterior spinal cord. Mean half-maximal concentrations of HCNP and free-HCNP in AcCho synthesis of medial septal nuclei culture were 1.0 +/- 0.3 x 10(-10) M and 1.0 +/- 0.6 x 10( 11) M, respectively. Affinity purified polyclonal antibody to the free-HCNP neutralized the activity of crude hippocampal extract, as well as synthetic HCNP and free-HCNP. These observations suggested that HCNP was present in the hippocampal extract and was involved in development of specific cholinergic neuron in central nervous system. PMID- 1611511 TI - AV3V lesion suppresses the pressor, dipsogenic and natriuretic responses to cholinergic activation of the septal area in rats. AB - In the present study we investigated the effect of anteroventral third ventricle (AV3V) lesion on pressor, dipsogenic, natriuretic and kaliuretic responses induced by the injection of carbachol (a cholinergic agonist) into the medial septal area (MSA) of rats. Male rats with sham or AV3V lesion and a stainless steel cannula implanted into the MSA were used. Carbachol (2 nmol) injected into the MSA in sham lesion rats produced pressor (43 +/- 2 mmHg), dipsogenic (9.6 +/- 1.2 ml/h), natriuretic (531 +/- 82 microEq/120 min) and kaliuretic (164 +/- 14 microEq/120 min) responses. In AV3V-lesioned rats (1-5 days and 14-18 days), the pressor (11 +/- 2 and 14 +/- 2 mmHg, respectively), dipsogenic (1.9 +/- 0.7 and 1.4 +/- 0.6 ml/h), natriuretic (21 +/- 5 and 159 +/- 44 microEq/120 min) and kaliuretic (124 +/- 14 and 86 +/- 13 microEq/120 min) responses induced by carbachol injection into the MSA were reduced. These results show that the AV3V region is essential for the pressor, dipsogenic, natriuretic and kaliuretic responses induced by cholinergic activation of the MSA in rats. PMID- 1611512 TI - Pial arteriolar constriction following cortical spreading depression is mediated by prostanoids. AB - The mechanism of pial arteriolar constriction during post-cortical spreading depression (CSD) was examined in anesthetized adult rabbits. Using a closed cranial window and intravital microscopy, the diameter of a pial arteriole was determined. A single CSD was induced by KCl micro-injection and its propagation was monitored by recording slow potential changes accompanying CSD. Prostanoid levels in cortical cerebrospinal fluid (CSF) were determined by radioimmunoassay. Pial arteriolar diameter increased significantly from 76 +/- 6 to a maximum of 119 +/- 5 microns (57%, n = 8) for 1.6 +/- 0.1 min when CSD (velocity, 2.8 +/- 0.1 mm/min) reached the cortex just beneath the vessel irrespective of its location. Shortly after CSD expiration from the cortex, pial arteriolar diameter decreased from the pre-CSD level to a minimum of 67 +/- 5 microns (12%, n = 8) for 19.5 +/- 2.1 min. CSD was elicited again in the same animal while the cortical surface under the window was continuously superfused with artificial CSF at a flow rate of 3.2-4.5 ml/min. Pial arteriolar dilation (from 75 +/- 6 to 115 +/- 3 microns, 53 +/- 9%, for 1.6 +/- 0.1 min, n = 8) was observed again during CSD (velocity, 2.7 +/- 0.2 mm/min), however, no constriction of the vessel was seen after CSD expiration. Indomethacin pretreatment (n = 11) to inhibit prostanoid production enhanced the magnitude of CSD-induced vasodilation from the pretreatment levels of 59 +/- 9% (from 82 +/- 5 to 130 +/- 8 microns for 1.7 min) to the post-treatment levels of 82 +/- 13% (from 78 +/- 5 to 142 +/- 12 microns for 1.8 min).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611513 TI - The effects of dark-rearing on the electrophysiology of the rat visual cortex. AB - Our previous two studies have shown that dark-rearing affects the morphology and chemistry of adult rat primary visual cortex (area 17). In this study we demonstrate correlated physiological alterations with single unit recordings in the same preparation. Rats were raised from birth in either 14 h light/10 h dark (Lt/Dk) or in total darkness (Dk). At the age of 3 months, single units were recorded in area 17 of both groups. The cortical cells of Dk animals showed significantly more spontaneous activity during ambient lighting. The mean rate of randomly appearing spontaneous activity was greatly increased in Dk animals. Moreover, many cells in Dk animals also exhibited a particular type of spontaneous activity which occurred as 'bursts' of spikes, i.e. quantified groupings of fast firing spikes, separated by randomly appearing spontaneous activity. The mean number of bursts per min seen in Dk animals was also significantly more than any such activity seen in Lt/Dk animals. Visual stimuli consisted of white or dark bars moving with different orientations and directions at slow and fast speeds, and full field flashes. In response to moving stimuli, notably fewer cells were orientation- or direction tuned in dark-reared animals, and when they did respond to moving bar stimuli, the responses were of relatively longer duration. The pathologically high spontaneous activity rate, as well as lack of tuning and relatively prolonged duration of responses to moving stimuli indicate that intracortical inhibitory mechanisms are seriously compromised in both the unstimulated and stimulated states and is in agreement with our previous findings (Bakkum, B.W., Port, J.D., Cohen, R.S. and Benevento, L.A., Soc. Neursci. Abst., 15 (1989) 797) of a decreased number of synapses and GABA containing cells in the visual cortex of the same preparation. Other evidence suggests that there may be a decrease in stimulus-bound excitatory drive. Significantly fewer cells in Dk animals were excited by all visual stimuli, and responses elicited by flashes had relatively longer 'on' latencies, relatively shorter durations, and were generally weaker. This may correlate with our finding of a significantly smaller number of perforated postsynaptic densities in the cortex of the same preparation (Bakkum, B.W., Benevento, L.A. and Cohen, R.S., J. Neurosci. Res., 23 (1991) 65-80). PMID- 1611514 TI - Morphine place conditioning is differentially affected by CCKA and CCKB receptor antagonists. AB - In the present study we have examined the interaction between the selective cholecystokinin (CCK)A and CCKB receptor antagonists, devazepide and L365-260 on morphine conditioned place preference (CPP). Using an unbiased procedure, morphine (1.5 mg/kg) produced a reliable CPP which was observed irrespective of the conditioning compartment type. Pretreatment with devazepide (0.001-0.01 mg/kg s.c.) produced a dose related attenuation of this response. At higher doses (0.1 1 mg/kg) this antagonism became variable and dependent on the training compartment with blockade only observed when conditioning was to the white/rough textured environment. This profile has also been reported for the serotonin (5 HT)3 receptor antagonist ondansetron. The CCKB antagonist L365-260 (0.000001-0.01 mg/kg) failed to antagonize the morphine CPP, if anything a mild potentiation was observed. To study this further we examined the interaction between L365-260 (0.01 mg/kg) and a subthreshold dose of morphine (0.3 mg/kg). At these doses neither drug elicited CPP, however when co-administered a significant CPP was recorded. Finally, L365-260 at 1 mg/kg induced a mild but significant CPP when administered alone. These results suggest a differential role of CCK receptor subtypes on reward-related behaviour and complement previous studies suggesting bimodal effects of CCK systems on mesolimbic dopamine function. PMID- 1611515 TI - Neurophysiological, pharmacological and behavioral evidence for medial thalamic mediation of cocaine-induced dopaminergic analgesia. AB - These studies examined the effects of cocaine on thalamic neurons that respond maximally either to noxious or to innocuous somatic stimulation. Cocaine attenuated high intensity electrically-evoked nociceptive responses of all 25 units studied in the parafascicular and central lateral nuclei of the medial thalamus. A dose of 1 mg/kg intravenously (i.v.) suppressed medial thalamic unit discharge evoked by both noxious somatic stimulation (49.4 +/- 8.7% of control response) and spinal cord stimulation (76.2 +/- 6.6% of control response). The effect of cocaine on unit responses to noxious somatic stimulation was dose related in the range of 0.3-3.5 mg/kg i.v. and was attenuated by eticlopride, a D 2 selective dopamine receptor antagonist. Morphine also suppressed noxious somatic evoked responses of medial thalamic units in a dose-dependent manner. Units in the lateral (ventrobasal) thalamus (n = 4) that responded only to innocuous stimuli were not affected by cocaine at doses up to 3.5 mg/kg i.v. Ibotenic acid lesions in the parafascicular nucleus of the medial thalamus attenuated the analgesic effect of cocaine in the formalin test. These results suggest that both cocaine and the parafascicular nucleus interact with dopaminergic mechanisms that attenuate nociceptive spinal projections to the medial thalamus. PMID- 1611516 TI - The relationships between aging, monoamine oxidase, striatal dopamine and the effects of MPTP in C57BL/6 mice: a critical reassessment. AB - Although the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice have been reported to increase with age, they have not been characterized in the full spectrum of ages. Thus, in spite of a considerable body of scientific literature on the subject, previous reports leave unanswered the question of whether or not the increased susceptibility of fully mature mice is part of the aging process or simply a consequence of maturation. In the present study, the age-related effects of MPTP on striatal dopamine were studied in groups of C57BL/6 mice from young maturity to old age. The major increase in the effects of MPTP occurred between 2 and 10 months of age (equivalent to adolescence and young adulthood in humans). A slight additional increase was observed between 10 and 16 months (young adulthood and middle age) and the dopamine-depleting effects of MPTP significantly declined in truly aged animals (24 months). Of note also is the fact that normal concentrations of striatal dopamine did not decline in the later ages. Additional studies indicated that while neuronal sensitivity to the effects of 1-methyl-4-phenylpyridinium (MPP+; the putative toxic metabolite of MPTP) appears to remain constant, age-related changes in the activity of striatal monoamine oxidase type B (MAO B) paralleled the dopamine-depleting effects of MPTP in the 4 age groups. Indeed, MAO B activity increased between 2 and 16 months and declined slightly, but significantly, between 16 and 24 months. This pattern of age-related changes in MAO B, striatal dopamine and the sensitivity of the nigrostriatal system to toxic insult may provide insights into factors which have been implicated in age-related neurodegeneration and idiopathic Parkinson's disease. PMID- 1611517 TI - Rat pineal Gsa, Gia and Goa: relative abundance and development. AB - The adult rat pineal gland contains relatively high concentrations of Gsa, low amounts of both Gia and Goa, and undetectable levels of GTa. During development the amounts of 45 kDa Gsa and of Gia remain constant. In contrast, 42 kDa Gsa and Goa are nearly absent at birth and increase in abundance markedly thereafter. GTa is undetectable at any age. It would appear that multiple mechanisms regulate the expression of G-proteins in the pineal gland. PMID- 1611518 TI - Human auditory primary and association cortex have differing lifetimes for activation traces. AB - The magnetic field pattern over the temporal area of the scalp 100 ms following the onset of a tone burst stimulus provides evidence for neuronal activity in auditory primary and association cortices that overlap in time. Habituation studies indicate that onset and offset features of a tone produce activation traces in primary cortex that are at least partially common, but only the onset produces an appreciable trace in association cortex. The characteristic time constant for the decay of the latter's activation trace is several seconds longer than for the former. PMID- 1611519 TI - Kainic acid lesion of the striatum increases dopamine release but reduces 3 methoxytyramine level. AB - Kainic acid lesion of the striatum leads to the disruption of the striatonigral regulatory loop. Although microdialysis showed an increase in dopamine release, two days after kainic acid injection, 3-methoxytyramine levels are dramatically decreased. This suggests that the postsynaptic membrane-bound catechol-O methyltransferase (COMT), but not the glial COMT, is responsible for the formation of measured 3-methoxytyramine. PMID- 1611520 TI - Chronic intracerebral infusions of vasopressin and vasopressin antagonist modulate social recognition in rat. AB - To assess the role of androgen-dependent brain vasopressinergic transmission in the modulation of social recognition, castrated male rats which are deficient in vasopressin were implanted intracerebroventricularly with an Accurel collodion mini-device containing 10 micrograms vasopressin (AVP) whereas intact male rats were implanted with a similar device containing 50 micrograms of 1 deaminopenicillamine 2-O-methyltyrosine arginine vasopressin (dPTyr(Me)AVP), a specific antagonist of the vasopressor like receptors of vasopressin. Control rats in each experimental group were implanted with an Accurel device containing water. Castrated rats treated with AVP explored familiar juvenile conspecifics in the same manner as intact male rats. Conversely, intact male rats treated with dPTyr(Me)AVP explored familiar juveniles in the same manner as castrated male rats. These results confirm the role of androgen-dependent vasopressinergic neurotransmission in social recognition. PMID- 1611521 TI - Observations of synaptic efficacy and paired-pulse facilitation in area CA1 of hippocampal slices from coriaria lactone-kindled rats. AB - The changes of population spike(PS)/population excitatory postsynaptic potential (EPSP) slope relationship and paired-pulse facilitation (PPF) were primarily investigated with extracellular recording in stratum pyramidale to stimulation of Schaffer collaterals in CA1 region of hippocampal slices from coriaria lactone (CL)-kindled and control rats. The results were as follows: (1) neither spontaneous nor evoked epileptiform bursts were found in all hippocampal slices from CL-kindled and control rats; (2) the synaptic efficacy, expressed by the ratio of PS/EPSP slope, at low stimulation intensity ranging from 10-30% of its maximum was significantly increased on CL-kindled rats (P less than 0.05); and (3) although PPF was found in all slices, the PPF strength only at stimulation intensity of 10 and 20% of maximum was augmented remarkably in CL-kindled rats (P less than 0.002 and 0.024, respectively). According to the results from our previous work, we suggested that the increment of PS/EPSP slope ratio and PPF strength at low stimulation intensity may result from the potentiation of excitatory synaptic activity or/and the change of intrinsic excitability of pyramidal neurons. PMID- 1611522 TI - Anticonvulsant effect of liposome-entrapped superoxide dismutase in amygdaloid kindled rats. AB - Amygdaloid-kindled rats received intravenous human copper-zinc superoxide dismutase (CuZn-SOD) either in free form or entrapped within liposomes (SOD-L), at 5, 10 or 20 mg/kg. The animals were stimulated at the generalized seizure triggering threshold 5 min, 2 h and then every 24 h after the drug was given, until 5 consecutive stage 5 seizures were induced. Free CuZn-SOD had little or no effect. However, SOD-L, particularly at 10 mg/kg, had a prolonged anticonvulsant effect, although there was great individual variation in the onset and duration of seizure suppression. This effect of SOD-L may be due to the ability of liposomes to act as a depot for the sustained release of drugs. PMID- 1611523 TI - The quantitative autoradiographic distribution of [3H]MK-801 binding sites in the normal human brainstem in relation to motor neuron disease. AB - The distribution of N-methyl-D-aspartate (NMDA) receptors in the normal human brainstem has been investigated using MK-801. Specific [3H]MK-801 binding showed a heterogeneous distribution, the greatest density of binding sites being found in the substantia nigra, locus coeruleus, and the hypoglossal and inferior olivary nuclei. Brainstem motor nuclei subserving eye movements, which tend to be spared in motor neuron disease (MND), had significantly lower densities of binding compared to other cranial nerve motor nuclei (V, VII, X, XII) which tend to be affected. The anatomical distribution of NMDA receptors may be one factor determining selective vulnerability to excitotoxic injury. PMID- 1611524 TI - Effects of nicotine on spatial memory deficits in rats with septal lesions. AB - Impaired septohippocampal function has been implicated in the memory deficits associated with Alzheimer's disease (AD), and septal lesions have been used to model the cognitive deficits associated with AD. In this study, we assessed the effects of systemic administration of nicotine on lesion-induced deficits in the acquisition of a spatial discrimination version of the Morris water maze. Rats with radiofrequency lesions of the medial septum were required to learn which of two visible platforms in a pool of water provided a means of escape. On each of the first 4 days of training, the rats received an injection of (-)nicotine (0, 0.1 or 0.3 mg/kg, i.p.) before training. Nicotine markedly improved the performance of septal rats. This enhanced performance was maintained in rats subsequently tested 1 and 15 days later without additional drug treatment. Septal rats initially trained under nicotine were impaired, however, when the platform locations were reversed and training was conducted under saline. Our findings suggest that nicotinic receptor stimulation might be useful in the treatment of cognitive deficits. PMID- 1611525 TI - Organization of taste-evoked activity in the hamster parabrachial nucleus. AB - Small groups of 3-4 neighboring taste neurons in the hamster parabrachial nucleus (PBN) were either generalists (42%) or specialists (58%). Generalists responded well to sucrose, NaCl, KCl, and their mixture but specialists responded to only one or two stimuli. PBN temporal response patterns resembled chorda tympani patterns, indicating that they were preserved across two synapses. Generalist neuron-groups were distributed throughout the central medial (CM) subdivision of PBN. Sucrose-sensitive neuron-groups, which responded best to mixtures, were restricted to rostral CM, whereas most NaCl-best neuron groups were in caudal CM. These results suggest a multifaceted functional organization of taste sensibilities in the PBN. PMID- 1611526 TI - Effects of ovariectomy and estrogen replacement on dye coupling among rat supraoptic nucleus neurons. AB - Among magnocellular neurosecretory neurons (MNCs), the frequency of dye coupling, and thus also of electrotonic coupling, is reduced in male rats following castration. Testosterone replacement prevented this reduction suggesting a modulatory role for gonadal steroids. To determine whether gonadal steroids in females influenced coupling incidence, Lucifer yellow CH injections were made in MNCs in slices taken from ovariectomized rats, either untreated or implanted with capsules containing estradiol-17 beta or estradiol-17 alpha, or from sham operated rats. In groups without biologically active estradiol, incidence of dye coupling was increased by 138-169% over those with normal plasma levels, as measured by radioimmunoassay. We conclude that estradiol and testosterone have opposite effects on coupling frequency among MNCs and that the facilitatory effects of testosterone in males are unlikely to be via its aromatization to estrogen. PMID- 1611527 TI - Cortical hypoperfusion following spreading depression is not altered by tirilazad mesylate (U-74006F) in awake rats. AB - The 21-aminosteroid antioxidant tirilazad mesylate (U-74006F) blocks the delayed hypoperfusion associated with spreading cortical depression (SCD) in anesthetized rats. Because the resting vascular tone influences the blood flow response to SCD, the effect of this drug was reassessed in awake rats. In this state, tirilazad mesylate did not eliminate cerebral hypoperfusion following SCD. Oxygen radical-induced lipid peroxidation may not mediate cerebral hypoperfusion after SCD in awake rats. PMID- 1611529 TI - Testosterone improves maze performance and induces development of a male hippocampus in females. AB - In a combined behavioral and morphometric study, we observed a testosterone related sexual dimorphism in the granule cell layer of the hippocampus of Sprague Dawley rats that appears to be related to sex differences in spatial performance. This cell layer was larger and laterally asymmetrical in males. Neonatal testosterone treatment of females resulted in a more male-like hippocampus. These treated females also performed better than controls, and as well as males, on a spatial navigation task. In addition, a strong correlation between the size of granule cell layers and maze performance was detected. PMID- 1611528 TI - Decreased synthesis of ciliary neurotrophic factor in degenerating peripheral nerves. AB - The mRNA for ciliary neurotrophic factor in normal and injured sciatic nerves has been assayed by an RNase protection assay. The endoneurial concentration of ciliary neurotrophic factor mRNA is diminished in the distal nerve stump within three days of sciatic nerve transection, is less than one tenth of normal after one week, and remains low if regeneration does not occur. The synthesis of ciliary neurotrophic factor in injured peripheral nerves is decreased when and where the synthesis of nerve growth factor is increased. PMID- 1611530 TI - Calbindin-like immunoreactivity in two peripheral chemosensory tissues of the rat: taste buds and the vomeronasal organ. AB - In the rat, calbindin-like immunoreactivity was observed at both the light and electron microscopic levels within the chemoreceptor neurons of the vomeronasal organ (VNO) and both intragemmal cells and associated nerve fibers of the circumvallate taste buds. All VNO neurons were immunoreactive. Only a subset of intragemmal taste cells was immunoreactive; associated immunoreactive nerve fibers were apposed to both labeled and unlabeled cells but no synaptic contacts were observed. PMID- 1611531 TI - Unilateral enucleation alters vasoactive intestinal polypeptide-like immunoreactivity in the suprachiasmatic nucleus of the rat. AB - Adult Sprague-Dawley rats were unilaterally enucleated under deep anesthesia and sacrificed 3-11 months post-operatively. The brains were removed and the suprachiasmatic nuclei were evaluated for vasoactive intestinal polypeptide (VIP) like immunoreactivity. Our data show that expression of VIP is reduced in the nucleus that is deprived of retinal input. PMID- 1611533 TI - Calbindin immunoreactivity in normal human temporal neocortex. AB - Calbindin immunoreactivity in the temporal neocortex was examined in 4 subjects with no neurological, metabolic or malignant disease. The brains were obtained between 1 and 4 h after death and rapidly fixed by perfusion with 4% paraformaldehyde through the carotid arteries, cut into slabs, cryoprotected and stored at -80 degrees C. Sections of the whole left temporal lobe obtained with a freezing microtome were processed free-floating with a well known monoclonal antibody against calbindin according to the peroxidase-antiperoxidase (PAP) method. Calbindin-immunoreactive (CaBP-ir) neurons were found to be local-circuit neurons (interneurons) mainly distributed in the upper cortical layers (layers I, II and III), and were categorized as small multipolar neurons with ascending dendrites ramifying in the molecular layer, small bitufted cells, pyramid-like cells in layer II, horizontal neurons in the molecular layer, multipolar neurons with long descending dendrites, and large double-bouquet cells, some of them exhibiting a very long dendrite with claw-shaped terminals in layer V. Less than 10% of all CaBP-ir neurons were localized in the remaining cortical layers. Pyramidal cells were only very weakly or not stained at all. In addition, CaBP-ir fibres formed a dense plexus in the molecular layer, and vertical bundles 8-10 microns thick and 500-600 microns long, separated by blank spaces 20-40 microns wide were distributed in layers III and V/VI.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611532 TI - Transplantation of embryonic serotonin immunoreactive neurons into the transected spinal cord of adult monkey (Macaca fascicularis). AB - Five adult monkeys (Macaca fascicularis) underwent a total section of the spinal cord at the thoracic level (T6). Four of them received a daily treatment with cyclosporin (10 mg/kg). Ten days later, two animals treated with cyclosporin and one without cyclosporin received at T8 and T10 levels an injection of a cell suspension prepared from the rhombencephalon of a 40-day-old macaque embryo. Two control animals received one injection of Hank's balanced salt solution. The animals were sacrificed after 2 months (one grafted and one control) and 3 months (two grafted and one control), and their spinal cord was processed for the immunocytochemical detection of serotonin using light and electron microscopy. After 2 months of survival, serotonergic neurons had survived and developed within the transplant. Three months after transplantation, in the animal treated with cyclosporin, serotonergic neurons were found to survive with their axons growing into the host grey matter and establishing axosomatic and axodendritic synapses in the ventral horn. If the graft was isolated in the white matter no fibers were seen invading the grey matter. PMID- 1611534 TI - Changes in intracellular pH of mouse hippocampal slices responding to hypoxia and/or glucose depletion. AB - Effects of hypoxia and/or glucose depletion on apparent intracellular pH, (pHi)app, were studied in hippocampal slices of mouse brain using the fluorescence pH indicator BCECF (2',7'-bis(carboxyethyl)carboxyfluorescein). In the presence of glucose (11 mM), (pHi)app of the CA1 pyramidal cell layer decreased with hypoxia but rapidly recovered with reoxygenation. The response in (pHi)app to hypoxia was consistent with changes in lactate content. By superfusion with a hypoxic and glucose-devoid solution, (pHi)app decreased in the first 5 min, but then increased in two phases: during a 5- to 7-min period and again during the latter period of superfusion. BCECF fluorescence rapidly diminished in this latter period. These changes in (pHi)app could not be explained only by the lactate content in the slices. Some other mechanisms may also regulate the (pHi)app in the slices during and after hypoxia and glucose depletion. PMID- 1611535 TI - Regulation of acetylcholine release in vivo from rat hippocampus by monoamines as revealed by novel column-switching HPLC with electrochemical detection. AB - To clarify monoaminergic regulation of acetylcholine (ACh) release in the rat hippocampus, the effects of administration of monoamines through a dialysis probe on extracellular ACh levels were examined using in vivo brain microdialysis combined with a novel column-switching HPLC system. Infusion of dopamine or 5 hydroxytryptamine, but not noradrenaline, increased ACh levels. The ACh levels also increased following infusion of apomorphine and 5-methoxy-N,N dimethyltryptamine. These results demonstrate that hippocampal ACh release is regulated by dopamine and 5-hydroxytryptamine. PMID- 1611536 TI - c-fos may code for a common transcription factor within the hypothalamic neural circuits involved in osmoregulation. AB - Conscious rats were given an intraperitoneal (i.p.) injection of isotonic or hypertonic saline, and killed 10-240 min later. In the hypothalamus of hypertonic saline-injected rats, c-fos-mRNA positive cells were mainly restricted to the supraoptic and paraventricular nuclei and to structures associated with the lamina terminalis of the third ventricle, including in particular the subfornical organ, the organum vasculosum of the lamina terminalis (OVLT) and the median preoptic nucleus. These structures comprise the proposed anterior hypothalamic 'osmoreceptor complex' for regulation of vasopressin release. The time course of the appearance and disappearance of c-fos mRNA signals was similar in all regions. Thus c-fos protein (Fos) may be a common transcription factor in the hypothalamic neural circuits involved in osmoregulation. PMID- 1611537 TI - Effects of superior olivary complex lesions on binaural responses in rat inferior colliculus. AB - Unilateral or bilateral lesions of the superior olivary complex (SOC) were made by local injection of kainic acid through a micropipette lowered stereotaxically into the rat's auditory brainstem. The lesions had the effect of destroying cell bodies in the superior olive without disrupting fibers of passage. After a recovery period of approximately one month, physiological recordings were made with tungsten micro-electrodes from the central nucleus of the inferior colliculus of animals with SOC lesions. For animals with unilateral lesions recordings were made either ipsilateral or contralateral to the site of damage. Results were compared with data from normal control cases. Monaural and binaural tone bursts were presented through a sealed sound delivery system and binaural interaction patterns were determined. Both binaural summation and suppression responses were still present following unilateral SOC lesions. Interaural intensity difference thresholds were within the normal range and no differences were found between animals with lesions placed ipsilateral or contralateral to the recording site. Binaural summation and suppression responses were also present following bilateral lesions. Bilateral lesions had the effect of shifting the average interaural intensity difference thresholds in favor of the contralateral ear. But, in general, binaural interactions were remarkably little affected by bilateral destruction of the SOC. PMID- 1611539 TI - The autoinhibitory feedback control of acetylcholine release in human neocortex tissue. AB - Slices of human neocortex prelabelled with [3H]choline were superfused and stimulated electrically (3 Hz, 2 ms, 24 mA) in order to investigate the autoreceptor-mediated modulation of acetylcholine (ACh) release. The concentration-response curve of the muscarinic agonist oxotremorine (pKd = 6.76 +/- 0.06), which was equipotent to ACh, was shifted to the right in a parallel manner by atropine (pA2 = 8.56 +/- 0.11), as evaluated by non-linear regression analysis. Calculation of the biophase concentration of ACh showed that no ACh could be assumed to be present under these conditions, whereas following inhibition of the acetylcholinesterase by physostigmine (0.1 microM) a biophase concentration of 10(-6.89 +/- 0.11) M was estimated. The depression of ACh release due to physostigmine and tacrine, another anticholinesterase, was antagonized by atropine. When the autoinhibition was operative atropine and the M2 subtype specific muscarinic antagonists, AF-DX 116 and methoctramine, significantly increased the release of ACh whereas the 'facilitatory' effects of the M1 and M3-specific drugs, pirenzepine and hexahydrosiladifenidol, were not significant. Although different disinhibitory effects of the subtype-specific antagonists were found, they did, however, not show a pattern which would allow a clear characterisation of the subtype of muscarinic receptor associated with the autoreceptor. The release of ACh from neocortex tissue of the (non-demented) neurosurgical patients decreased with their age. This finding is consistent with the hypothesis that the normal aging process resembles a delayed and attenuated disease process of senile dementia of Alzheimer's type.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611540 TI - New aeroallergens in agricultural and related practice. PMID- 1611538 TI - Maternal stimulation affects the number of motor neurons in a sexually dimorphic nucleus of the lumbar spinal cord. AB - The role of maternal stimulation in the development of a lumbar motor nucleus (spinal nucleus of the bulboca vernosus, SNB) was investigated. The perineum, which has afferents to the lumbar region, is stimulated throughout early development by maternal licking, a behavior that is elicited by chemosignals secreted by the pups. In the present study, half of the dams were treated with intranasal zinc sulfate throughout the postpartum period, which led to a specific reduction in maternal stimulation of pup perineum by interfering with the reception of eliciting signals. Adult offspring of both sexes from anosmic dams had 11% fewer SNB motor neurons than normally stimulated controls, an effect which was most apparent in the rostral portion of the nucleus. There was no effect of treatment on neuron size. It was concluded that afferent input provided by species-typical maternal behavior contributes to the number of neurons that survive the neonatal period of normal cell death. PMID- 1611541 TI - The association of hypersensitivity diseases with dermatophyte infections. PMID- 1611542 TI - Allergens of storage mites. PMID- 1611543 TI - Novel steroid-based inhibitors of lung inflammation. PMID- 1611544 TI - A double-blind controlled trial of hyposensitization to Dermatophagoides pteronyssinus in children with atopic eczema. AB - A double-blind controlled trial of hyposensitization with tyrosine-adsorbed Dermatophagoides pteronyssinus vaccine in 24 children with atopic eczema and immediate hypersensitivity to D. pteronyssinus failed to demonstrate superiority over placebo after a standard 8 month course of treatment. In a second phase, children initially administered active treatment were randomly allocated to continue with active treatment or switched to placebo for a further 6 months. The clinical scores suggest that prolonged hyposensitization may be more effective than placebo but the numbers were too small to permit confident conclusions. A dramatic placebo effect may have served to conceal any additional therapeutic effect from active treatment. PMID- 1611545 TI - Purification and characterization of Lep d I, a major allergen from the mite Lepidoglyphus destructor. AB - A major allergen of the storage mite Lepidoglyphus destructor (Lep d I) has been purified by affinity chromatography using an anti-Lep d I monoclonal antibody. The purity of the protein obtained by this procedure was assessed by reverse phase HPLC. Lep d I displayed a molecular weight of 14 kD on SDS-PAGE under non reducing conditions, and 16 kD in the presence of a reducing agent. Analytical IEF revealed a little charge microheterogeneity, showing three bands with pIs 7.6 7.8. Purified Lep d I retained IgE-binding ability, as proved by immunoblotting experiments after SDS-PAGE and RAST with individual sera from L. destructor sensitive patients. Results from the latter technique demonstrated that 87% of L. destructor-allergic patients had specific IgE to Lep d I, and a good correlation between IgE reactivity with L. destructor extract and Lep d I was found. In addition, RAST inhibition experiments showed that IgE-binding sites on Lep d I are major L. destructor-allergenic determinants, since Lep d I could inhibit up to 75% the binding of specific IgE to L. destructor extract; on the other hand, Lep d I did not cross-react with D. pteronyssinus allergens. PMID- 1611547 TI - Comparison between MAGIC LITE- and CAP-system: two automated specific IgE antibody assays. AB - The MAGIC LITE system, a newly developed immunochemiluminometric assay for specific and total IgE antibody using paramagnetic particles coupled with standardized allergens as solid phase, was compared to the CAP system, a recently introduced immunoassay based on a cellulose polymer encased in a capsule. A total of 357 serum samples of patients with suspected inhalant allergies and a positive skin prick test (SPT) to common allergens (birch, timothy-grass, mugwort, cat dander, Dermatophagoides pteronyssinus, Alternaria) were investigated. Fifty SPT negative subjects served as controls (total number of tests in each assay = 1600). Both assays were highly precise (overall intra-assay and inter-assay coefficients of variation were 2.9% and 4.5% in MAGIC LITE, 4.7% and 5.5% in CAP) and showed excellent linearity (mean r2 of eightfold log2 serum dilutions were 99.7% and 99.3% in MAGIC LITE and CAP). Good correlations were found between the absolute specific IgE antibody values detected by both methods (correlation coefficient r: birth 0.86, grass 0.93, mugwort 0.96, cat 0.91, D. pteronyssinus 0.73, Alternaria 0.90). Excellent specificity (greater than or equal to 98%) occurred in both assays and with all allergens, and sensitivity was related to the allergen (MAGIC LITE/CAP): birch 91%/89%, grass 83%/90%, mugwort 50%/69%, cat 83%/83%, D. pteronyssinus 72%/78%, Alternaria 75%/81%. Our results indicate that both in vitro tests are useful tools for the detection of specific IgE antibody. PMID- 1611546 TI - Protein and allergen content of commercial skin test extracts for soybeans. AB - The protein and allergen contents of four commercial soybean skin test extracts were tested by SDS-PAGE and immunoblotting using sera from soy-allergic adults. Polyacrylamide gels stained with Coomassie Blue showed an absence of several major soybean proteins, particularly those at higher molecular weights. The acidic subunits of glycinin and beta-conglycinin, major soybean storage proteins, appear to be absent or present in much reduced amounts. Immunoblots with soy allergic sera indicate alteration, reduction, or loss of IgE-binding in the commercial extracts as compared to extracts of soy flour. In one soy-allergic patient, skin tests revealed a negative response to three of the commercial soybean extracts and a mild response to one extract. Defatted soy flour obtained from two of the four extract manufacturers was extracted in the laboratory using a standard procedure for the isolation of soybean proteins. In one case, the extract still had an abnormal protein profile on gel electrophoresis while in the other case, the new extraction procedure gave significantly improved extraction of soy protein. Preparation methods appear to be partially responsible for the variable allergen content in commercial soybean skin test extracts. PMID- 1611548 TI - Group V allergens in grass pollens: IV. Similarities in amino acid compositions and NH2-terminal sequences of the group V allergens from Lolium perenne, Poa pratensis and Dactylis glomerata. AB - Monoclonal antibodies (PpV4) raised against Phleum pratense group V allergen were used for immuno-affinity chromatography of cross-reacting group V allergens from related grass species. Fractions enriched in group V allergen were obtained from Lolium perenne, Poa pratense and Dactylis glomerata extracts. The major components in these fractions were found in the Mwr range 25-28 kD. IgE binding to these components was shown using a pool of grass allergic sera, by SDS-PAGE immunoblotting. These fractions were electroblotted from tricine SDS-PAGE gels onto a polyvinylidene-difluoride membrane and selected group V bands were directly cut out and used for amino acid analysis and NH2-terminal sequencing. Both the amino acid compositions and the NH2-terminal sequences obtained for each group V allergen were almost similar to each other and to the sequence and composition of the previously described allergen Phl p V from Phleum pratense. A common trait of the investigated allergens, is the very high contents of alanine (25-32%) and the presence of the modified amino acid, hydroxyproline. PMID- 1611549 TI - The association of perennial rhinitis with Trichophyton infection. AB - Trichophyton was recently reported to be the cause of respiratory allergy in patients with severe bronchial asthma. We describe eight patients with perennial rhinitis in combination with skin or toe-nail infection, in whom Type I hypersensitivity reaction to Trichophyton was confirmed by skin test, RAST and nasal provocation. When treated with oral fungicidal therapy, there was significant improvement in both their skin and nasal symptoms. Local therapy produced only a mild, transient improvement. We emphasize the need for thorough evaluations in patients with respiratory allergies and negative routine skin tests. PMID- 1611550 TI - Oilseed rape--a new allergen? AB - Oilseed rape (Brassica napus) is a commonly grown crop in Europe and it has been suggested that its pollen may be a potent new allergen. The prevalence of sensitization in a normal exposed population and an objective study of those patients found to be allergic to the rape pollen is described. The results show a low prevalence of allergy to oilseed rape pollen (less than 0.2%) unless the subjects were occupationally exposed. Those affected, with one exception, were already atopic and allergic to other pollens. The role of volatile materials given off by the plant remains to be elucidated. PMID- 1611551 TI - Is the determination of cord blood total IgE levels any value in the prediction of atopic disease? PMID- 1611552 TI - Detection and disinfection of pathogens in storm-generated flows. AB - The disease-producing potential of recreational waters is currently estimated through the use of certain bacterial indicators that are believed to be positively correlated with the presence of fecal contamination. In general, these indicators and their recommended limiting values have been adopted for use from existing standard methods for the analysis of sanitary waste water. However, no indicator currently in use today exists solely in the feces of man and not also elsewhere, e.g., in soils, vegetation, and the feces of animals. Storm-water runoff is often rich in bacteria originating from these nonhuman sources and can contain high densities of indicator bacteria; however, existing epidemiological studies of recreational waters receiving storm-water runoff have reported little correlation between current indicator densities and the incidences of swimming illnesses. In addition, microbial analyses of storm-water runoff have revealed a predominance of nonenteric disease-causing bacteria and viruses that have been linked to respiratory illnesses and skin infections. Fecal-based indicators in use today provide no information on the risks resulting from body contact with these nonenteric pathogens. Consequently, for receiving waters containing discharges that originate primarily from separate storm drainage systems, current bacterial indicators are ill suited to accurately assess the water's total illness-producing capabilities. This paper briefly reviews the development of current bacterial standards and evaluates their adoption in the field of storm water testing. The unique disinfection requirements of storm-generated runoff are discussed, and advanced disinfection practices are reviewed. The need for additional epidemiological studies that address the disease-causing potential of nonhuman and nonenteric pathogens commonly found in storm-water runoff from urban, agricultural, and rural watershed areas is emphasized in order to determine the actual health risks associated with storm water runoff contact. PMID- 1611553 TI - Isolation and biological activities of endotoxin from Leptospira interrogans. AB - Endotoxins extracted with ethylenediaminetetraacetate (EDTA) from Leptospira interrogans serovars icterohaemorrhagiae and canicola and Leptospira biflexa serovar patoc were tested for various biological activities characteristic of endotoxins. The presence of lipopolysaccharide biological activity was demonstrated by the Limulus amoebocyte lysate test, pyrogenicity in rabbits, complement interaction inhibiting the erythrocyte lysis, and chicken-embryo lethality. The lipopolysaccharides did not induce the local Shwartzman reaction. The lipopolysaccharides of serovars icterohaemorrhagiae and canicola were immunogenic in rabbits and were cytotoxic to chicken-embryo fibroblasts. PMID- 1611554 TI - Utilization of chymotrypsin as a sole carbon and (or) nitrogen source by Escherichia coli. AB - alpha-Chymotrypsin serves as a sole carbon source, sole nitrogen source, and as sole carbon plus nitrogen source for wild-type Escherichia coli in a totally defined medium. Hence, a mammalian host for E. coli may supply the necessary carbon and nitrogen nutrients for the microorganism. Growth is most rapid when chymotrypsin is a sole nitrogen source and least rapid with chymotrypsin as a carbon source. The approximate doubling times for E. coli utilizing chymotrypsin as a nitrogen source, carbon plus nitrogen source, and carbon source are 1.6, 4.6, and 11.3 h, respectively. The activity of the residual enzyme in the culture supernates falls off asymptotically over the source of time, as followed by cleavage of glutaryl-L-phenylalanine-p-nitroanilide. Chymotrypsin hydrolyzes succinyl-L-ala-L-ala-p-nitroanilide, the elastase substrate, to some extent. Peptidases do not appear to be secreted that hydrolyze such model substrates as benzoyl-DL-arginine-p-nitroanilide, the tryptic and cathepsin B substrate, L leucine-p-nitroanilide, the leucine amino-peptidase substrate, or L-lysine-p nitroanilide, the aminopeptidase B substrate. Growth of E. coli is generally directly related to the loss of chymotryptic activity in the medium. Hence, autolysis of chymotrypsin, i.e., self-degradation, is an important factor for the availability of degradation products of the enzyme to the bacterium for growth purposes. Accordingly, the degradation of a host protein by autolysis presents an opportunity for E. coli to survive during periods of host nutritional crisis by utilization of the degradation peptides that are produced during autolysis. PMID- 1611555 TI - Nitrogenase activity and growth of Frankia in batch and continuous culture. AB - Frankia grown in batch culture was unable to maintain a high rate of nitrogenase activity and, once a peak level was reached, activity rapidly declined. Addition of 5 mM carbon source of cultures or transfer to fresh medium was followed by brief recovery of nitrogenase activity. The extent of recovery decreased as additions or transfers were made to progressively older cultures. Daily addition of fresh medium (dilution rate = 0.125 day-1) allowed Frankia to be maintained in continuous, derepressed culture with stable rates of growth and nitrogenase activity for more than 30 days. The proportion of active, mature vesicles also remained constant in continuous culture but decreased with time in batch culture. PMID- 1611556 TI - Occurrence of thermotolerant campylobacters in fresh vegetables sold at farmers' outdoor markets and supermarkets. AB - A total of 1564 fresh samples of 10 vegetable types from two different retail levels (533 samples from farmers' outdoor markets and 1031 samples from supermarkets) were surveyed for the occurrence of thermotolerant campylobacters. In samples from the outdoor markets, campylobacters were detected on six types of vegetables; the detection rates were spinach, 3.3; lettuce, 3.1; radish, 2.7; green onions, 2.5; parsley, 2.4; and potatoes, 1.6%. Campylobacter jejuni was the predominant species (88%), with the remainder being C. lari (8%) and C. coli (4%). When the outdoor market samples were thoroughly washed with chlorinated water, all were negative for campylobacters. Of the samples from supermarkets, all were negative for campylobacters whether purchased in summer or winter. These results suggest that vegetables sold at farmers' outdoor markets are produced and (or) stored under less sanitary conditions than those sold at supermarkets, and they could constitute health hazards. Therefore, vegetables (e.g., potatoes and spinach) from farmers' markets must be decontaminated by washing with chlorinated water or cooked thoroughly before consumption. PMID- 1611557 TI - Changes in selected enzyme activities during growth of pure and mixed cultures of the white-rot decay fungus Trametes versicolor and the potential biocontrol fungus Trichoderma harzianum. AB - Two filamentous fungi, the white-rot fungus Trametes versicolor and the soil fungus and potential biocontrol organism Trichoderma harzianum, have been grown in pure and mixed cultures on low-N (0.4 mM) and high-N (4 mM) defined synthetic media to determine the activities of selected wood-degrading enzymes such as cellobiase, cellulase, laccase, and peroxidases. Growth characteristics and enzyme activities were examined for potential correlations. Such correlations would allow the use of simple enzyme assays for measuring biomass development and would facilitate predictions about competitiveness of species in mixed fungal cultures. Our results show that while laccase and Poly Red-478 peroxidase activities indicate survival of the decay fungus, none of the monitored extracellular enzymes can serve as a quantitative indicator for biomass accumulation. As expected, the level of available nitrogen affected the production of the enzymes monitored: in low-N media, specific cellobiase, specific cellulase, and peroxidase activities were enhanced, while laccase activities were reduced. Most importantly, laccase activities of Trametes versicolor, and to a smaller extent, cellobiase activities of both fungi, were significantly induced in mixed cultures of Trametes versicolor and Trichoderma harzianum. PMID- 1611558 TI - Effect of substitution at C-6 on the susceptibility of pullulan to pullulanases. Enzymatic degradation of modified pullulans. AB - Pullulan, with all of the primary hydroxyl groups modified, is an excellent substrate for defining the effect of degree of substitution on biodegradability because of the uniform distribution of substituents on the polysaccharide. 6 Chloro-6-deoxypullulan and 3,6-anhydropullulan are highly resistant to hydrolysis by the four different types of pullulanase. 6-Azido-6-deoxypullulan is resistant to three types but susceptible to hydrolysis by the fourth, isopullulanase. Neopullulanase is strongly inhibited by 6-chloro-6-deoxypullulan and 6-azido-6 deoxypullulan, the other pullulanases much less so. PMID- 1611559 TI - In situ colonization of polyvinyl chloride, brass, and copper by Legionella pneumophila. AB - A sampling device (Robbins device) was used to expose brass, copper, and polyvinyl chloride plugs to potable water contaminated by Legionella pneumophila serogroup 1. Plugs were removed at approximately 1-week intervals and cultured. The colonization rates were polyvinyl chloride, 70; copper, 31; and brass, 25%. Quantitative cultures revealed that polyvinyl chloride was most heavily colonized, whereas brass was least colonized. We conclude that materials used in plumbing systems are readily colonized by Legionella and that the Robbins device provides a means for testing such materials in an in situ setting. PMID- 1611560 TI - Cytosolic and membrane-bound chitinases of two mucoraceous fungi: a comparative study. AB - Chitinases isolated from membrane and cytosolic fractions of two mucoraceous fungi, Choanephora cucurbitarum and Phascolomyces articulosus, were investigated. The membrane-bound chitinase was isolated by Bio-Gel P-100 and DEAE Bio-Gel A chromatographic techniques. On SDS-PAGE the chitinase from both fungi migrated as a single band of M(r) 66 kDa. The cytosolic chitinase from the mycelial extracts of these fungi was separated by heat treatment, ammonium sulphate precipitation, and by affinity chromatography with regenerated chitin. SDS-PAGE showed two bands for each fungus with M(r) of 69.5 and 55 kDa in C. cucurbitarum and M(r) 69.5 and 53 kDa in Ph. articulosus. Chitinases, membrane bound or cytosolic, hydrolyzed regenerated chitin, colloidal chitin, glycol chitin, N,N'-diacetylchitobiose, and N,N',N"-triacetylchitotriose. Heavy metals, inhibitors, and N-acetylglucosamine inhibited chitinase activity, whereas trypsin and an acid protease enhanced its activity. Chitinase preparations showed lysozyme activity that was inhibited by histamine but not by N-acetylglucosamine. There was no N-acetylglucosamanidase activity, but beta-1,3 glucanase activity was found in cytosolic preparations only. Despite slight differences in their molecular mass, both the membrane-bound and cytosolic chitinases showed similarities in substrate utilization, response to inhibitors, and activation by trypsin and acid protease; pH and temperature optima also were similar. PMID- 1611561 TI - Influence of metribuzin on the Rhizobium leguminosarum--lentil (Lens culinaris) symbiosis. AB - The effects of the triazine herbicide metribuzin (Sencor) on the lentil (Lens culinaris Medic.) - Rhizobium leguminosarum biovar viciae symbiosis were studied in Leonard jars and growth pouches. Lentils inoculated with Rhizobium leguminosarum strain 128C54 or 128C84, and noninoculated lentils grown in plant nutrient solution supplemented with 5 mM KNO3, had metribuzin applied to the plants at either 8 or 13 days after planting. When sprayed at 8 days, metribuzin had a significant (p less than or equal to 0.05) negative effect on plant weight, number of nodules, taproot growth, and acetylene reduction activity. Five to 10 days after spraying, the plants began to recover from the inhibitory effects. When spraying was delayed to 13 days after planting, metribuzin had little effect on plant growth. The R. leguminosarum strain used as inoculant affected the degree of inhibition of lentil growth and the rate of plant recovery. Less than 0.2% of foliarly applied metribuzin was translocated to the root. Thus the detrimental effects of metribuzin application to lentils were mainly due to direct effects on the plant, which resulted in indirect effects on nodulation and nitrogen fixation. PMID- 1611562 TI - A novel shuttle vector for Streptomyces spp. and Escherichia coli as a tool in site-directed mutagenesis. AB - This paper describes the construction and utilization of a novel shuttle vector for Streptomyces spp. and Escherichia coli as a useful vector in site-directed mutagenesis. The shuttle vector pIAFS20 (6.7 kb) has the following features: a replicon for Streptomyces spp., isolated from plasmid pIJ702; the thiostrepton resistance gene as a selective marker in Streptomyces; the ColE1 origin, allowing replication in E. coli; and the ampicillin-resistance gene as a selective marker in E. coli. Vector pIAFS20 also contains the phage f1 intergenic region, which permits production of single-stranded DNA in E. coli after superinfection with helper phage M13K07. Moreover, the lac promoter is located in front of the multiple cloning sites cassette, allowing eventual expression of the cloned genes in E. coli. After mutagenesis and screening of the mutants in E. coli, the plasmids can be readily used to transform Streptomyces spp. As a demonstration, a 3.2-kb DNA fragment containing the gene encoding the xylanase A from Streptomyces lividans 1326 was inserted into pIAFS20, and the promoter region of this gene served as a target for site-directed mutagenesis. The two deletions reported here confirm the efficiency of this new vector as a tool in mutagenesis. PMID- 1611563 TI - Chiropractic manipulation. PMID- 1611564 TI - Chiropractic manipulation. PMID- 1611565 TI - Chiropractic manipulation. PMID- 1611566 TI - Patients and pharmaceutical companies. PMID- 1611567 TI - Intravenous immune globulin use in children. PMID- 1611569 TI - Hockey helmets instead? PMID- 1611568 TI - Alcohol metabolism. PMID- 1611570 TI - Women and breast cancer: is it really possible for the public to be well informed? PMID- 1611571 TI - Quality of care: 1. What is quality and how can it be measured? Health Services Research Group. PMID- 1611572 TI - So few medical schools, so many clerk rating systems! PMID- 1611573 TI - Update on AIDS worldwide. PMID- 1611574 TI - Determining success in the cholesterol crusade. PMID- 1611575 TI - Style in medical writing. 1911. PMID- 1611576 TI - Health care system must adapt to meet needs of multicultural society, MDs say. PMID- 1611577 TI - Cultural awareness part of the health care agenda at Toronto Hospital. PMID- 1611578 TI - [The separation of Quebec could be disastrous for research in Canada, say the experts]. PMID- 1611579 TI - CMA databank contains a wealth of information on MDs, practice patterns. PMID- 1611580 TI - [Use of the Adinfer diagnostic system in a study of somatic disorders in general practice]. AB - Somatic complaints are very common in general medical practice. They are not identified as psychic disorders and are treated symptomatically. We explore two kind of problems: 1. methodological problems such as the instruments to use to examine somatic complaints (it is evident that a checklist does not give the best results with suggestible patients); and 2. the relationships between somatic complaints and psychic disorders such as anxiety, depression and somatoform disorders. Psychiatric nosology is by no means clear and includes many diagnoses from "hysteria" to "hypochondria" or "psychosomatic", "somatization". In this study, we compare the symptoms collected by general practitioners, and their clinical diagnoses to those obtained by an automatic DSM-III diagnostic program. Adinfer was modified so that three DSM decision trees were systematically scanned: depressive, anxiety and somatoform disorders. This allows for an epidemiological study of somatic complaints and their relationship to depression and anxiety. The subjects' score on rating scales for anxiety and depression are compared with the diagnoses made by the expert system. We discuss the significance of somatic symptoms, the DSM classes and the value of expert systems in epidemiological studies. PMID- 1611581 TI - [Psychometric characteristics of the French Canadian version of a satisfaction scale for hospitalized psychiatric patients]. AB - This paper presents the results of a content and convergent validity study of the French-Canadian version of a standardized satisfaction scale for hospitalized psychiatric patients. One hundred and twenty-two patients underwent an interview during which they completed the translated version of the Client Satisfaction Questionnaire, developed by Distephano et al, and answered open-ended questions on their satisfaction with the services they received. The results revealed strong correlations between these measures of satisfaction and a high level of internal consistency for the Distefano scale, suggesting satisfactory psychometric characteristics for this French version. As for the original questionnaire, the factorial structure yielded at least two distinct satisfaction dimensions. These results, and those of the content analysis, based on answers from the open-ended questions, helped to identify aspects mentioned by the patients but not covered by the items included in the satisfaction scales. The units' cleanliness, therapists' work and attitudes and privacy on the units are examples of these dimensions. PMID- 1611582 TI - Psychiatric disorders in children. PMID- 1611583 TI - Child psychiatry and early intervention: I. The aggregate burden of suffering. AB - This paper discusses the need to estimate the costs of an illness to properly allocate intervention resources for the various psychiatric disorders of childhood. Disorders that require the most community resources should be given the highest priority for early intervention programs. Factors to consider for estimating disorders which are most costly are discussed here: the incidence of the disorder, its severity, whether it is episodic or stable, and its impact on the individual family and the community. These factors contribute to the aggregate burden of suffering caused by a disorder. PMID- 1611584 TI - Child psychiatry and early intervention: II. The internalizing disorders. AB - This paper uses the concepts introduced in the paper Child Psychiatry and Early Intervention: I. The Aggregate Burden of Suffering to review the internalizing disorders of childhood. This review surveys the internalizing disorders from the point of view of early intervention, for their prevalence, course, risk, early indicators, associated impairment, and responses to intervention. In general, the internalizing disorders have little effect on the community. When coupled with other disorders such as conduct disorder, or when dealing with suicide, the community's concern for these disorders increases and allocation of resources to target populations who are at risk becomes an important public health goal. PMID- 1611585 TI - Child psychiatry and early intervention: IV. The externalizing disorders. AB - This paper is the last in a series of four using the concept of the aggregate burden of suffering to review the major psychiatric disorders of childhood. This paper reviews the externalizing disorders of childhood to prioritize early intervention programs. The paper discusses the prevalence, course, risk and early indicators, associated impairments, and responses to intervention. The externalizing disorders affect the individual, family and community and are thought to result in the greatest aggregate burden of suffering of all the childhood mental disorders. Early intervention is advocated and will likely need to be intense and long term for this group of children. The need for research into efficient and effective programs is emphasized. PMID- 1611586 TI - Behavioural problems among preschool age children in Shanghai: analysis of 3,000 cases. AB - This paper reports the preliminary findings of an epidemiological study of 3,000 children ages four and five in the Shanghai area. Associations were investigated between problems in the narrow band syndromes of the Achenbach Child Behavior Checklist and certain sociodemographic variables (a one-child family, other social circumstances related to the family). No strong evidence emerged of a distinct psychopathology associated with children from single-child families, although there was a significant correlation between being an only child and having social withdrawal problems. Delinquent behaviour and hyperactivity were more frequent among boys, while somatic complaints, schizoid or anxious, and depression were more frequent among girls. A four year follow-up study of 433 children from the original group who continued to have problems showed a marked increase in hyperactive syndrome problems; this suggests the existence of a clinically identifiable group of behaviourally disturbed children. Early identification allows for early treatment and comparison of the relative efficacy of early and late treatment approaches. PMID- 1611587 TI - Planning mental health services: II. Current Canadian initiatives. AB - A brief overview of recent policy developments across Canada and a discussion of the common themes and challenges they address demonstrates the scope of activity in this field. The federal level of mental health planning and a summary of recent of policy developments in each province are described. Significant progress has been made in Canada in the development of mental health services since deinstitutionalization. Major challenges remain, however, which are being addressed to varying degrees across the country. The challenges related to the key issues of major mental illness, integration and consumerism are illustrated. PMID- 1611588 TI - Abduction during custody and access disputes. AB - In recent years abductions during divorce custody and access disputes have received greater attention from both the lay and medical press. However, little has been written on the psychopathology of the abductors or the impact on children of being kidnapped by a parent. In this study 20 cases of abduction, involving 20 parents and 37 children, were examined after the children had been located and returned to the custodial parent. Characteristics of the abduction and psychopathology seen in the children are compared to those of a control population. The outcome of assessments conducted by the family court clinic after the abductions are profiled. PMID- 1611589 TI - Charles Bonnet hallucinations: a case series. AB - Charles Bonnet hallucinations are complex visual hallucinations which occur during clear consciousness in patients who do not suffer from psychosis, substance abuse, sleep disorders, focal neurological lesions or acute eye disease. They are well-defined images of patterns, scenes, animals or humans combined with normal perceptions and elicit a neutral or pleasant emotional response. Because of conflicting reports about cognitive or visual impairments among patients with these hallucinations, I describe the cognitive and visual status of 13 patients. One patient had preserved cognition and vision; three had preserved cognition and impaired vision; three had impaired cognition and preserved vision; and six had both impaired cognition and vision. It is unlikely that cognitive or visual deficits alone caused the hallucinations, but may have contributed to a state of sensory deprivation with visual phenomena. PMID- 1611590 TI - Encephalitis associated with herpes zoster: a case report and review. AB - This paper describes the case of a patient with a history of affective disorder who developed encephalitis associated with herpes zoster which presented as a delirium with prominent manic symptoms. Published reports of encephalitis following herpes zoster infections are reviewed. The diagnosis of herpes zoster associated encephalitis should be suspected in individuals with changes in his or her mental state, an abnormal electroencephalogram and an abnormal cerebrospinal fluid examination which closely follow a cutaneous herpes zoster lesion. PMID- 1611591 TI - Adverse effects of switching from fluoxetine to desipramine. PMID- 1611592 TI - Folie a deux and mental retardation. PMID- 1611593 TI - Inhibition of sulfotransferase in primary cultures of human hepatocytes affecting metabolism and binding of 2-acetylaminofluorene. AB - The metabolism and DNA binding of acetylaminofluorene (AAF) was investigated in human hepatocytes that were isolated from donor liver tissue by collagenase perfusion. Hepatocytes were treated with 0.01 microM pentachlorophenol (PCP), as a sulfotransferase inhibitor, to investigate the role of sulfotransferase in human bioactivation of aromatic amines. Concentrations of PCP greater than 0.1 microM resulted in cytotoxicity as noted by detachment of cells and atypical morphology. The metabolites of AAF were identified by HPLC as aminofluorene, 7-OH AAF, 9-OH-AAF, 5-OH-AAF, N-OH-AAF, 1-OH-AAF and 3-OH-AAF. No consistent alteration in the metabolites produced occurred with PCP treatment compared to controls. PCP treatment increased total DNA binding of AAF metabolites compared with controls, suggesting that sulfotransferase does not activate AAF in human hepatocytes. Inhibition of sulfotransferase in human hepatocytes does not decrease DNA binding of AAF metabolites as noted previously with rat hepatocytes. Therefore, PCP may inhibit a detoxication pathway. This study supports N,O acyltransferase as the critical enzyme for the formation of the major reactive metabolite in human liver. PMID- 1611594 TI - Effect of dietary curcumin and ascorbyl palmitate on azoxymethanol-induced colonic epithelial cell proliferation and focal areas of dysplasia. AB - Curcumin, a major yellow pigment of turmeric obtained from powdered rhizomes of the plant Curcuma longa Linn., is commonly used as a coloring agent in foods, drugs and cosmetics. Ascorbyl palmitate is a lipid soluble derivative of ascorbic acid. Both curcumin and ascorbyl palmitate have antioxidant activity and are potent inhibitors of 12-O-tetradecanoyl-phorbol-13-acetate-induced tumor promotion in mouse skin. The effects of dietary curcumin and ascorbyl palmitate on azoxymethanol (AOM)-induced hyperproliferation of colonic epithelial cells and the incidence of focal areas of dysplasia (FADs) were evaluated in female CF-1 mice fed an AIN 76A diet. Subcutaneous injections of AOM (10 mg/kg body wt. once weekly for 6 weeks) caused hyperplasia and the formation of FADs in the colon. Administration of 2% curcumin in the diet inhibited AOM-induced formation of FADs while administration of 2% ascorbyl palmitate in the diet did not demonstrate inhibition. This result suggests that dietary curcumin may inhibit AOM-induced colonic neoplasia in mice. PMID- 1611595 TI - Protection by N-acetylcysteine of the histopathological and cytogenetical damage produced by exposure of rats to cigarette smoke. AB - Adult male Sprague-Dawley rats were exposed whole-body to mainstream cigarette smoke (CS) once daily for 40 consecutive days. Such a treatment resulted in a significant decrease of body weight growth and in intense histopathological changes of terminal airways, including a severe inflammation of bronchial and bronchiolar mucosae, with multiple hyperplastic and metaplastic lesions and foci of micropapillomatous growth as well as emphysema, with extensive disruption of alveolar walls. All histopathological changes were efficiently prevented by the daily administration of the thiol N-acetyl-L-cysteine (NAC) by gavage. Cytological and cytogenetical changes were monitored in bronchoalveolar lavage (BAL) fluid and bone marrow cells of groups of rats killed after 1, 3, 8, 28, or 40 days of treatment. From the first day of exposure, CS significantly enhanced the proportion of polymorphonucleates among BAL cells and the frequency of micronucleated (MN) bone marrow polychromatic erythrocytes. After 8 days, a reduction was observed in the polychromatic/normochromatic erythrocytes ratio and an increase in the frequency of MN pulmonary alveolar macrophages (PAM) was also recorded, followed, after 28 days, by an increase of binucleated PAM. All these alterations immediately reached a plateau and persisted unchanged until the end of the experiment. NAC administration exhibited a significant and considerable protective effect towards the CS-induced alterations of BAL cellularity, the increase of MN PAM and bone marrow cytotoxicity. PMID- 1611596 TI - Salivary nitrate and nitrite concentrations from a sample population of children and adults in high risk area for esophageal and gastric cancers in Kashmir, India. AB - Salivary nitrate and nitrite levels in a sample population of children and adults from a high risk area of esophageal and gastric cancer in Kashmir are reported. In different age groups mean levels of salivary nitrate/nitrite ranged between 21 36 ppm and 12-17 ppm, respectively. PMID- 1611597 TI - DNA adduct formation in mice following treatment with used engine oil and identification of some of the major adducts by 32P-postlabelling. AB - Used engine oil from a petrol-powered vehicle was fractionated by column chromatography into seven parts for which the major polycyclic aromatic hydrocarbon (PAH) components were determined by GC. Topical treatment of mice with the fractions and 32P-postlabelling of the skin DNA resulted in the detection of multiple adduct spots on TLC for some, but not all, of the fractions. The majority of the DNA binding capacity of the used engine oil was possessed by the first three fractions, (equivalent to 25, 15 and 14.5%, respectively) of the adduct forming ability of the unfractionated oil. The chromatographic mobilities of the adduct spots induced by these fractions were compared to those produced by unfractionated used engine oil. In addition, mice were also treated topically with reference PAHs, either singly or as mixtures, dissolved in unused oil at the concentrations at which they were present in the used oil. Comparisons were made between the chromatographic mobilities of the adducts formed in mouse skin DNA by synthetic mixtures with those formed by the used oil. From these data, some of the major adducts produced by treatment with used engine oil are suggested to be formed by reactive metabolites of benzo[b]naphtho[1,2-d]thiophene, benzo[c]phenanthrene, benzo[g,h,i]fluoranthene, chrysene, benzo[a]pyrene and benzo[g,h,i]perylene. PMID- 1611599 TI - Can a non-tumorigenic dose of carcinogen cause two or more errors in a cell? AB - Cancer is believed to be the result of a multistep process, beginning with a single alteration in a cell's genome. Here the hypothesis that a few cells may receive two or more hits after the application of a non-tumorigenic or higher dose of carcinogen is proposed. Preneoplastic lesions that arise from such doubly hit cells may be few in number, but may more easily undergo tumor formation and tumor progression. This hypothesis augments the multihit model of carcinogenesis and explains much data that the single, first-hit assumption cannot. PMID- 1611598 TI - Initiating activity of 1,1,2,2-tetrachloroethane in two-stage BALB/c 3T3 cell transformation. AB - By using in vitro two-stage BALB/c 3T3 cell transformation assay, we have tested the effect of promoting treatment with tetradecanoylphorbol acetate (TPA) on transformation induced by 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE). Cells were treated with subeffective or transforming concentrations of 1,1,2,2-TTCE in the presence of an S9-mix activating system, followed by TPA promoting treatment. The transforming activity of 1,1,2,2-TTCE is evident only by reseeding confluent cells and allowing additional rounds of cell replications in the amplification test. Treatment with TPA leads to a marked transformation yield in all plates scored even at the lowest assayed dosage of 1,1,2,2-TTCE, without performing amplification of transformation. PMID- 1611600 TI - Lack of modifying effects of 6-mercaptopurine in a medium term bioassay system for liver carcinogenesis using male F344 rats. AB - Carcinogenic and modification potential of 6-mercaptopurine (6-MP) was studied in a medium-term bioassay system for rat liver carcinogenesis. F344 male rats were initiated with a single dose (200 mg/kg body wt.) of diethylnitrosamine (DEN) i.p. and fed diets containing either 0.005% or 0.02% 6-MP with or without 0.05% phenobarbital (PB) for 6 weeks. Quantitative data revealed that 6-MP did not enhance the appearance of enzyme-altered preneoplastic foci and nodules even when administered at the highest dose (0.02%) despite showing an immunosuppressive effect and slight liver cell damage. Neither of the doses of 6-MP exerted any significant influence on the enhancing effect of PB when administered simultaneously in the medium-term-bioassay. PMID- 1611601 TI - The meaning of quality of life for bone marrow transplant survivors. Part 1. The impact of bone marrow transplant on quality of life. AB - Quality of life (QOL) is an important concept in cancer nursing and has particular significance for bone marrow transplant (BMT). BMT survivors are faced with the demands of acute transplant symptoms as well as chronic illness demands posttransplant. The purpose of this study was to explore the concept of QOL for BMT survivors and to gain understanding of nursing interventions that may improve QOL in this population. The conceptual framework for this study was derived from the model of QOL developed by Ferrell, Grant, and Padilla (1989) that depicts the QOL domains of physical well-being, psychological well-being, social concerns, and spiritual well-being. This qualitative study consisted of a one-time interview of 119 BMT survivors using six open-ended questions. The items were based on previous research of the authors and content validity was established by a panel of BMT experts. Content analysis was performed on verbatim written responses to six questions regarding BMT and QOL. Part one of this two-part report provides analysis based on the questions regarding the meaning of QOL to BMT survivors and the impact of BMT on QOL. PMID- 1611602 TI - Family assessment in an oncology setting. AB - Nurses who care for oncology patients are in a unique position to observe and assess how the family is managing this stressful experience. Families under stress can create obstacles to delivering optimal nursing care, resulting in feelings of powerlessness on the part of the nurse. This article proposes a family life-cycle framework for assessing families. The concept of centripetal and centrifugal modes constructively links the illness life cycle to the individual and family life cycles. Recommended psychosocial interventions using this model are addressed. PMID- 1611603 TI - Care needs of home-based cancer patients and their caregivers. Quantitative findings. AB - The purpose of this study was to identify care needs of home-based patients receiving treatment for cancer and their caregivers. The sample consisted of 30 patients receiving radiation therapy and/or immunologically based treatments for a variety of cancers and 29 caregivers. Patient and caregiver needs scales were used to elicit the needs of patients and caregivers. Patients and caregivers were able to cite their unique needs. Patients had more needs for themselves in the areas of personal care, activity management, and interpersonal interaction than did the caregivers. The necessity for individualization of care was noted by both patients and caregivers, an area that nursing is in a unique position to address. PMID- 1611604 TI - Treatment for radiation-induced xerostomia. An innovative remedy. AB - Xerostomia continues to be a major complaint of patients who have had radiation therapy of the salivary glands and neck. This article describes the advantages and disadvantages of conventional treatment methods and introduces an innovative, yet inexpensive remedy that has produced favorable results for those afflicted with this chronic complication of therapy. PMID- 1611605 TI - Relationships between oral mucositis and treatment variables in bone marrow transplant patients. AB - The pattern of oral mucositis and related treatment variables was studied in 20 bone marrow transplant patients. Patients received either total body irradiation (TBI) or busulfan in combination with cyclophosphamide and etoposide as pretransplant conditioning. Daily oral assessment scores were analyzed. Mucosal changes began approximately 2 days before transplant and peaked approximately 8 days after transplant. There was a trend for patients receiving TBI to have slightly higher oral scores during the first week posttransplant than patients receiving busulfan. The TBI patients averaged almost twice the number of days of continuous intravenous morphine infusion for oral pain and 6 additional days of total parenteral nutrition when compared with patients receiving busulfan. Subjects who died during aplasia manifested mucositis that gradually worsened and did not return to baseline. Differences in oral status based on type of transplant, either autologous or allogeneic, were not shown in this study. PMID- 1611606 TI - Information guide for patients receiving total body irradiation before bone marrow transplantation. AB - Most patients with hematologic malignancies are conditioned for bone marrow transplantation with a regimen that includes the use of total body irradiation. This patient information guide was put together to simplify and standardize the type of instructions that patients receive before total body irradiation and to provide information for nurses who care for patients receiving such treatment. Content includes common questions asked by patients and families; a description of possible side effects; when side effects begin; and the patient's role in minimizing side effects. PMID- 1611607 TI - International directory of cancer nursing educational experiences and professional organizations. 1992. Developed by the board of directors and members of the International Society of Nurses in Cancer Care. PMID- 1611609 TI - Cerebral blood flow and oxygen metabolism in infants with hydrocephalus. AB - In this study, regional cerebral blood flow (rCBF) and the cerebral metabolic rate of oxygen (rCMRO2) were measured using positron emission tomography (PET) with oxygen-15 radiopharmaceuticals to clarify the pathophysiology of ventriculomegaly in the developing brain. Four hydrocephalic infants without severe neurological deficit were studied. Hypoperfusion was observed in the frontal, parietal, and visual association cortices which surrounded dilated anterior or posterior horns of the lateral ventricle. Lower rCMRO2 values than adult rates were observed in all cases. In the infants with markedly enlarged anterior or posterior horns, the surrounding cortices showed relatively lower rCMRO2 values with the fall of rCBF. Postoperative studies were performed in two infants. rCMRO2 increased in every region after ventriculoperitoneal shunting, but little change was observed in rCBF. These results indicate that metabolic deterioration occurs in the developing brain with hydrocephalus. PMID- 1611608 TI - Hydrodynamics in vein of Galen malformations. AB - Forty-three patients with vein of Galen aneurysmal malformations (VGAM) referred to us for endovascular treatment between 1985 and 1990 and 335 additional cases published in the literature were reviewed with particular attention to the presence of ventricular enlargement and outcome after shunting. Hydrocephalus was the second most frequent symptom (46.8%); it is more frequent in infants (73%) than in children, adults (30%) or neonates (15%). Of the patients reported in the literature, 17.9% had undergone shunting. Within the shunted population there was an overall morbidity of 41% and a mortality of 10% (especially in the infant group). In our series 17 patients (39.5%) were shunted and a significant difference in the clinical outcome was noted between the shunted and the nonshunted group. Of the nonshunted patients, 66.6% were free of any neurological deficit or mental retardation and fewer than 5% presented with significant mental retardation. On the other hand, only 33.3% of the shunted patients had a favorable outcome and more than 15% developed significant mental retardation. Among the various causes of hydrocephalus in patients with VGAMs, such as obstruction of the aqueduct, subarachnoid hemorrhage, or ex vacuo hydrocephalus, high venous pressure may be of particular importance. In this article a physiopathological interpretation of the hydrodynamics in VGAMs is developed and a speculative explanation for CSF disorders related to ventricular shunting proposed. Treatment of hydrocephalus in VGAMs can be achieved through obliteration of the malformation or at least diminishing the venous pressure; surgical ventricular shunting does not have to be the first treatment of hydrodynamic disorders associated with VGAMs, especially in infants. PMID- 1611610 TI - Doppler flow velocities in children with controlled hydrocephalus: reference values for the diagnosis of blocked cerebrospinal fluid shunts. AB - Doppler flow velocities in the middle cerebral artery of children with blocked cerebrospinal fluid shunts show changes that can be used as a non-invasive method for assessing shunt function. The velocities also change with age, and the purpose of this study was to define a reference range of values for children with controlled hydrocephalus. Flow velocities were measured in 248 asymptomatic children with shunts and an age-reference range was derived. Twenty children were subsequently admitted with suspected shunt malfunction and 11 of these required a shunt revision. On admission 9 of the 11 children requiring operation had Doppler values outside the reference range, whereas none of the children whose symptoms settled without surgery had abnormal values. The reference range will facilitate the use of transcranial Doppler for the assessment of children with suspected shunt malfunction. PMID- 1611611 TI - Sphenoidal electrode insertion under local analgesia in children. AB - The indications for method and the results of sphenoidal electrode insertion under local analgesia are evaluated in children. This technique makes it possible to study the hippocampal area, which cannot be studied by other extracranial electrodes. It also localizes in a temporal lobe some complex seizures without electrical events on surface recordings, complex seizures with bilateral temporal spikes or a frontotemporal focus of spikes, as well as those with a temporal focus with bilateral synchronous spikes in standard EEG. Therefore, sphenoidal electrodes inserted without heavy general analgesia enable temporal seizures to be identified and localized, leading to more specific neuroradiological and neurophysiological explorations and helping in this way to select possible patients for epileptic surgery. PMID- 1611612 TI - Treatment of early recurrent medulloblastoma in children with cisplatin and etoposide: a preliminary report. AB - The prognosis of recurrent medulloblastoma remains extremely poor. Combination chemotherapy with cisplatin (CDDP) and etoposide (VP-16) was given to five children with early recurrent medulloblastoma. As a rule, CDDP 20 mg/m2 per day and VP-16 60 mg/m2 per day were administered intravenously for 5 days. This cycle was repeated three times at 4-week intervals. After this therapy, cerebellar signs improved in one case and were unchanged in four cases. Weakness and sensory disturbance, however, improved in three of four patients. Moreover, neck and/or back pain resolved in all these four. Radiological findings improved in three cases. Myelosuppression appeared in all patients, but receded rapidly. No other significant complications were noticed. Two patients died 5 and 6 months after this therapy. These results seem to suggest that this therapy has a use in improving neurological symptoms, particularly neck and/or back pain, although its efficacy is limited. PMID- 1611614 TI - The probable role of hydrocephalus in the development of intraventricular septa. An observation of one case. AB - Multiloculated cerebral ventricles are a well-known complication of neonatal meningitis secondary to gram-negative bacteria. Their presence often hampers the proper functioning of the multiple shunts required for draining the ventricles. To determine whether the associated hydrocephalus may contribute to the development of the ventricular septa, we analyzed the histological structure of the ventricular wall and of the ventricular septa of a child who died as a consequence of Escherichia coli meningitis and unilateral hydrocephalus. Our results show that the ventricular septa are formed by glial protrusion into the ventricles. The ependymal wall of the grossly dilated ventricle was disrupted, but not that of the contralateral ventricle. We hypothesize that the presence of an insufficiently controlled hydrocephalus may have been one of the factors that induced the formation of the septa. It is suggested that an external ventricular derivation should be used during the active phase of the infection. PMID- 1611613 TI - Intracranial lesions of surgical interest in minor head injuries in paediatric patients. AB - Among 62 children and adolescents (1-16 years) admitted over a period of 3 years (1987-1989) with a minor head injury, 33 (53%) were found to harbour intracranial lesions of surgical interest. The most frequent lesion found was extradural haematoma (17 cases), followed by cerebral contusion (7 cases), depressed fracture (4 cases), depressed fracture with underlying contusion (3 cases) and pneumocephalus (2 cases). A skull fracture was present in 88% of patients with an intracranial lesion and in 50% of patients without lesions. Fifteen patients underwent surgery for an extradural haematoma or a depressed fracture. All had a good recovery. No correlation was found between age and Glasgow Coma Score on the one hand, and the incidence of both the presence of intracranial lesions and the necessity of surgical treatment on the other. The only important risk factor proved to be a skull fracture, which had occurred significantly more often in patients with intracranial lesions than in those without any. PMID- 1611615 TI - Cryptogenic osteomyelitis of the skull and intracerebral abscess. AB - The authors report a rare case of cryptogenic osteomyelitis of the skull with an intracerebral and a subgaleal abscess. Total excision of the abscess extending from the cortical surface to the lateral ventricle led to ventriculitis and subgaleal cerebrospinal fluid collection. These complications could have been avoided by aspirating the abscess after removing the infected portion of the skull and the epidural granulation tissue. Neurosurgeons preferring to excise such an abscess should leave a small area of capsule at the base in order to avoid having to open the ventricle. PMID- 1611616 TI - Multiple extracranial meningiomas in a child. AB - Meningioma is an uncommon tumour in childhood. We report the case of a child presenting with proptosis, which proved to be due to an optic nerve sheath meningioma. Subsequently, he complained of back pain and stiffness, and upon investigation this was also revealed to be due to a meningioma. PMID- 1611617 TI - XX Annual Meeting of the International Society for Pediatric Neurosurgery. Prague, 3-6 June 1992. Abstracts. PMID- 1611618 TI - Tumor-immunotherapy with the use of tumor-antigen-pulsed antigen-presenting cells. AB - Our previous study demonstrated that the administration of antigen-presenting cells (APC) pulsed with tumor cell membrane fraction to naive syngeneic mice results in effective induction of tumor-specific protective immunity in vivo. The present study examined whether tumor-antigen-pulsed APC can produce the inhibitory effect on the growth of tumor cells when administered to tumor-bearing hosts. Naive BALB/c mice were inoculated with viable tumor cells. Five days later, these mice started to receive the relevant tumor-antigen-pulsed APC at 3- to 4-day intervals. The administration of tumor-antigen-pulsed APC induced the rejection or growth inhibition of a growing tumor in approximately half of the recipient mice. Moreover, it was demonstrated that tumor-specific immunity was induced in such tumor-regressed mice. These results indicate that tumor-antigen pulsed APC are effectively applicable to the tumor-specific immunotherapy. PMID- 1611620 TI - Antitumour efficacy of lymphokine-activated killer cells loaded with ricin against experimentally induced lung metastases. AB - Adoptive transfer of tumour-specific T lymphocytes loaded with ricin into tumour bearing mice exerts a transient therapeutic effect against locally induced tumours [Cerundolo et al. (1987) Br J Cancer 55: 413]. As transferred cells preferentially locate in the lung, we studied the therapeutic effect of ricin loaded, lymphokine-activated killer (LAK) cells on lung metastases induced by M4 or B16-F1 (F1) tumour cell injection. In vitro studies demonstrated that ricin treated LAK cells were about 100-fold more efficient than untreated LAK cells in inhibiting growth of the ricin-sensitive M4 tumour cell line. This effect was most likely due to the released ricin, as treated and untreated LAK cells inhibited the relatively toxin-resistant F1 cell line to the same extent. Ricin treatment did not alter the tissue distribution of intravenously (i.v.) injected LAK cells, which selectively localized in the lung early after inoculation, whether or not metastases were present. Adoptive transfer experiments showed that ricin-treated LAK cells were significantly more efficient than untreated LAK cells in inhibiting M4- but not F1-induced lung metastases. These results indicate that LAK cells are able to deliver a therapeutic concentration of antineoplastic compounds directly to the lung. PMID- 1611619 TI - Studies of a tumor-associated antigen, COX-1, recognized by a monoclonal antibody. AB - Monoclonal antibodies against an ovarian tumor cell line, OC-3-VGH, were generated using modified hybridoma technology. Among the seven that were selected for their high specificity and affinity to ovarian cancer cells and low cross reactivity to most normal human tissues, RP 215 was shown to react specifically with a tumor-associated antigen, COX-1, from certain ovarian/cervical cancer cell lines. By Western blot assay, COX-1 was shown to have a subunit molecular mass of about 60 kDa and exist as an aggregate in the native state. COX-1 could also be detected in the shed medium of certain cultured tumor cells. A solid-phase sandwich enzyme-immunoassay procedure was designed for quantitative determinations of COX-1 in the shed medium or in patients' sera using RP 215 for both well-coating and the signal detection. Highly purified COX-1 was obtained from the shed medium of cultured OC-3-VGH tumor cells mainly by hydroxyapatite and immunoaffinity chromatography with RP 215 as the affinity ligand. At neutral pH, purified COX-1 also exists as an aggregate and is relatively stable at temperatures below 50 degrees C. Its immunoactivity was found to decrease with time in the presence of trypsin. However, the immunoactivity of COX-1 was not affected upon incubation with carbohydrate-digestive enzymes or concanavalin A and only partially inactivated in the presence of NaIO4 or iodoacetamide. Treatments of COX-1 with dithiothreitol and guanidine thiocyanate resulted in a complete loss of activity. Furthermore, rabbit antisera raised against purified COX-1 exhibited similar immunospecificity to that of RP 215. The results of this study suggest that COX-1 is a glycoprotein consisting of a 60 kDa subunit, which is recognized by RP 215 through its peptide determinant. Preliminary retrospective clinical studies were performed to assess the utility of a COX-1 enzyme immunoassay kit for detection and monitoring of patients with ovarian and cervical cancers. PMID- 1611621 TI - Induction of antitumor activities in spleen cells from mice and rats activated with lipopolysaccharide immobilized on beads. AB - Lipopolysaccharides (LPS) were coupled to polystyrene beads in order to apply the LPS without toxicity. The antitumor activity of the LPS-immobilizing beads was studied in experiments in vitro and in vivo. In vitro studies showed that spleen cells from C3H/HeN mice stimulated by beads immobilizing LPS from Escherichia coli produced cytolytic activity as strong as that of lymphokine-activated killer (LAK) cells. Spleen cells from Sprague-Dawley rats stimulated by beads immobilizing LPS from Salmonella minnesota produced cytolytic activity stronger than that of LAK cells. However, spleen cells stimulated by beads immobilizing each component of the LPS separately could not induce cytolysis. Contact stimulation, even for a brief period, sufficed for cytolytic activity, and was enhanced by culture for 48-72 h. Through in vivo studies, the suppression of tumor growth and a prolongation of the survival time were observed in tumor bearing mice injected with spleen cells activated by beads immobilizing LPS from E. coli, and in mice injected with LAK cells. The effect of the activated spleen cells was stronger than that of the LAK cells. In rats bearing metastatic tumors, spleen cells activated by beads immobilizing LPS from S. minnesota suppressed lung metastases more strongly than did LAK cells. These findings indicate that LPS immobilized by beads induced killer cells more strongly than interleukin-2. Ex vivo immunomodulation with LPS-immobilizing beads can be applied usefully as an anticancer treatment. PMID- 1611623 TI - Recombinant interleukin-2 treatment in patients with metastatic colorectal cancer: effect on natural cytotoxicity. AB - Natural cytotoxicity (natural killer, NK, and lymphokine-activated killer, LAK, activity) was documented in 12 patients with metastatic colorectal cancer, both before and after a 5-day course of continuous therapy with intravenous recombinant interleukin-2 (rIL-2). Treatment induced a substantial increase in circulating CD56+ lymphocytes (pretreatment: 12.1 +/- 6.9%, mean +/- SD; posttreatment: 39.2 +/- 6.9%. Maximal NK cell activity was induced by treatment with rIL-2 but only suboptimal augmentation of LAK cell cytotoxicity was obtained. This study indicates that although continuous infusion of rIL-2 does have a significant effect on natural cytotoxicity, this is suboptimal and further studies are necessary to define the most efficacious immunity-enhancing regimens of therapy, thereby hopefully improving clinical outcome of rIL-2 treatment. PMID- 1611622 TI - The loss of class II MHC antigen expression by ras-transformed murine fibroblasts passaged as tumours correlates with increased tumorigenicity but is not mediated by T cells. AB - In several murine tumour systems, expression of class II major histocompatibility complex (MHC) antigens by tumour cells, either constitutive or inducible, correlates with reduced tumorigenicity as compared with equivalent class-II negative cells, and CD4 phenotype T cells together with interferon gamma (which induces the expression of class II) may be involved in the control of the proliferation of class-II-expressing tumours. This implies a potential T-cell mediated selection pressure against class II expression. To test this possibility, we have repeatedly passaged as tumours in euthymic, syngeneic mice ras-transformed murine fibroblast lines, which are class-II-inducible, to determine whether class-II-non-inducible variants are selected. We examined the expression of both class I and class II antigen in tumour cells re-established in vitro. It was found that the inducibility of class II, but not class I, expression rapidly diminished, correlating with augmented tumorigenicity. However, this loss of class II inducibility occurred in athymic as well as euthymic mice. Therefore, despite the fact that the tumorigenicity of these lines is augmented in euthymic mice depleted of CD4 T cells or interferon gamma, we found no evidence of T-cell-mediated selection against class II expression. The loss of class II expression observed must be due to mechanisms other than immune selection. The possibility that this might result from other soluble factors modulating the response to interferon gamma in vivo is discussed. PMID- 1611624 TI - GD3-reactive antibodies can inhibit the lysis of autologous tumor cells by tumor infiltrating lymphocytes. AB - GD3 is expressed in high concentrations on melanoma cells and may serve as a useful target antigen for mAb-mediated immunotherapy. Monoclonal antibodies (mAbs) against GD3 stimulate cell-mediated immune responses against tumor cells in vitro and this activity may contribute to antitumor effects in patients with melanoma treated with GD3-reactive mAbs. In the present study the effects of GD3 reactive mAbs on autologous tumor cell lysis by a human melanoma-derived tumor infiltrating lymphocyte (TIL) population were examined. Unlike results reported for other GD3+ T cells isolated from melanoma patients, the tumor-specific lytic activity of the TIL line was inhibited by incubation with mAbs against GD3. Other melanoma-reactive mAbs, including those against GD2 and the high-molecular-weight melanoma-associated Ag, had no effect on the TIL lytic activity. Overall, these results indicate that mAbs against GD3 may have different effects on T cell/tumor cell interactions. PMID- 1611625 TI - Chemo-immunotherapy of murine solid tumors: enhanced therapeutic effects by interleukin-2 combined with interferon alpha and the role of specific T cells. AB - The aim of the present study has been to assess the therapeutic efficacy of various cytokines, singly or in combination, with and without chemotherapy (cyclophosphamide, Cy), in mice carrying advanced, weakly immunogenic tumors (MCA 105 sarcoma, M109 carcinoma). Treatment of animals with i.p. growths or experimental pulmonary metastases began 8-18 days after i.p. or i.v. tumor cell inoculation respectively. None of the cytokines tested [interleukin-2 (IL-2), interferon alpha (IFN alpha), tumor necrosis factor alpha (TNF alpha) and macrophage-colony-stimulating factor (M-CSF)] nor Cy had by itself a significant curative effect. A synergistic therapeutic effect was obtained with IL-2 or IFN alpha (but not with TNF alpha or M-CSF) in combination with Cy. The most efficacious regimen (65%-90% cure of mice carrying i.p. tumors) was the combination of Cy+IL-2+IFN alpha. Preliminary experiments suggested that sequential administration of these cytokines might be more beneficial than concurrent administration. Following successful immunotherapy, long-term (3-6 months) survivors showed a tumor-specific resistance to a second tumor challenge and their spleen contained an increased number of specific antitumor cytotoxic T lymphocyte precursors (5- to 20-fold, compared to control mice). In vitro and in vivo cell-depletion experiments using monoclonal antibodies revealed that T cells (primarily CD8), but not NK cells, are crucial for the therapeutic effects. This study indicates that a potent specific antitumor T cell immunity can be elicited against advanced weakly immunogenic tumors by combining chemotherapy (Cy) with IL 2 and IFN alpha. PMID- 1611626 TI - Photo-immunotargeting with haematoporphyrin conjugates activated by a low-power He-Ne laser. AB - A combined method has been developed for selective cytolysis in vitro as well as in vivo using a photosensitizer haematoporphyrin-protein conjugate as the targeting molecule and low-power He-Ne laser (632.8 nm) irradiation in order to activate the sensitizer to its excited, toxic triplet energy state. The specificity of the procedure was demonstrated in vitro by purging a mixed cell population from one component, and in vivo in an animal (nude mice) xenograft tumour model, where human cancer cells were destroyed by the immunotargeting method using monoclonal-antibody-haematoporphyrin (mAb-HP) conjugate (a-PNAr-I mAbs, which bind to the cell surface antigens of gastric cancer cells) and soft laser irradiation. The cell destruction was dependent on the doses of both mAb-HP and He-Ne laser light energy, and occurred only in target cell populations. PMID- 1611627 TI - Effector molecules from antitumor macrophages induced with OK-432 and cyclophosphamide. AB - The present study was designed to determine whether antitumor activity of macrophages induced with OK-432 and cyclophosphamide was mainly dependent on their ability to produce a soluble factor, that is, L-arginine-dependent nitric oxide as measured by nitrite concentration. Nitrite production by peritoneal macrophages from NIH Swiss mice pretreated with OK-432 (125 KE/kg) i.p. twice at 1-week intervals and with cyclophosphamide (200 mg/kg) i.p. 2 days before the second OK-432 treatment, increased with time for 24 h, and proportionally depended on macrophage numbers. Nitrite production was inhibited by actinomycin D and puromycin but not by mitomycin C. NG-Monomethyl-L-arginine, a specific competitive inhibitor of L-arginine-dependent nitric oxide synthesis, also inhibited production. There was a close correlation between nitrite production and antitumor activity in macrophages from mice pretreated with either OK-432 and cyclophosphamide, OK-432, or thioglycolate broth. OK-432 increased both nitrite production and antitumor activities when added to the macrophage from mice pretreated with OK-432 but not with thioglycolate broth. Both activities of macrophages from mice pretreated with OK-432 and cyclophosphamide were enhanced with increasing concentrations of L-arginine (0.125-1 mM) in the culture medium. D-Arginine, however, did not substitute for L-arginine. Neither activity was affected by contact between the macrophage and the EL4 cell. The macrophage showed antitumor activity through a membrane filter though the activity was greatly reduced. This antitumor activity of macrophages through a membrane was also inhibited by NG-Monomethyl-L-arginine, and increased by OK-432. However, conditioned media, obtained by culturing macrophages induced with OK-432 and cyclophosphamide, inhibited growth of EL4 cells. This activity was carried out by dialysable and non-dialysable factors. One of the dialysable factors was nitrite, an oxidized product of nitric oxide. The antitumor activity of non-dialysable factors was heat-stable and production of factors was increased by NG-Monomethyl L-arginine and OK-432. Also, non-dialysable factors increased both antitumor and nitrite production activities of OK-432-elicited macrophages, when incubated with factors. Such activity of factors was also heat-stable. The production of factors increased with incubation time of macrophages, and was not inhibited by NG Monomethyl-L-arginine. These results indicate that in vitro antitumor activity of macrophages induced with OK-432 and cyclophosphamide was mainly dependent on L arginine-dependent nitric oxide, and that macrophage-associated soluble factors other than nitric oxide were also needed to inhibit fully tumor growth in vitro. PMID- 1611629 TI - Acute inotropic response of rabbit papillary muscle to triiodothyronine. AB - The effects of triiodothyronine (T3) on the force frequency responses of isometrically contracting rabbit papillary muscles were studied in the presence of d-glucose, pyruvate or butyrate. The stimulation frequency was varied from 0.1 to 0.5 Hz, and the maximum developed tension and its maximum (Tmx) and minimum (Tmn) time derivative were measured. T3 concentrations ranged from 0.1 to 4.0 ng/ml. The addition of T3 resulted in a substrate-dependent increase in twitch tension; with the largest increases being: d-glucose 118 +/- 7%, pyruvate 143 +/- 6%, butyrate 123 +/- 11%; Tmx:d-glucose 121 +/- 8%, pyruvate 157 +/- 5%, butyrate 138 +/- 12%, and Tmn:d-glucose 150 +/- 10%, pyruvate 159 +/- 6%, butyrate 163 +/- 14%. All three measures of contractility showed a dose-dependent increase reaching a maximum value at a T3 concentration between 1 and 2 ng/ml. These data show that T3 induces an inotropic response in rabbit papillary muscles which is manifested within, approximately 30 min, and that the greatest increase is seen in Tmn. PMID- 1611628 TI - Effect of captopril therapy on lymphocyte potassium and magnesium concentrations in patients with congestive heart failure. AB - Lymphocyte potassium and magnesium were measured before and 3 months after the introduction of captopril in 18 patients taking diuretics for congestive heart failure. Compared to 32 healthy controls, 9 patients who had been on potassium supplements plus frusemide had decreased baseline lymphocyte magnesium and potassium concentrations (p less than 0.01), in spite of similar plasma electrolyte levels. There was a significant (p less than 0.01) increase in both lymphocyte potassium and magnesium levels after 3 months' treatment with captopril and frusemide in these patients. Nine patients who had been taking a potassium-sparing combination diuretic also had an increase in lymphocyte magnesium (p less than 0.05) following the introduction of captopril. Increased intracellular potassium and magnesium may be one mechanism whereby angiotensin converting enzyme inhibitors reduced arrhythmias and improve survival in patients with congestive heart failure. PMID- 1611630 TI - Combined carotid and coronary artery surgery: early and late results. AB - Patients with coronary artery disease can exhibit substantial vascular involvement; and vascular patients have a high incidence of coronary disease. Combined coronary artery bypass grafting (CABG) and treatment of extracranial cerebrovascular disease was performed in 52 patients, presenting strong indications for surgical treatment of coronary artery disease and symptomatic carotid disease and/or asymptomatic carotid bruit that reflected an ulcerative lesion or stenosis exceeding 75%. Overall hospital mortality was 3.8%. Clinical presentation determined the risk of the combined procedure: early mortality was much higher in urgent and emergency cases than in elective cases. Eight-year actuarial survival was 86%. This group of patients was compared with staged procedures in 45 patients (including carotid endarterectomy followed by CABG several weeks later) and with 42 patients who underwent coronary artery bypass in the presence of carotid bruits. Both early cardiac complications in the former group and neurologic complications in the latter were significantly more frequent than in combined procedures. Combined procedures can be performed with acceptable risk and with encouraging long-term results also in this special group of patients; they may improve the long-term prognosis of patients with diffuse atherosclerosis much more. PMID- 1611631 TI - Complications after intracoronary stent implantation: three cases. AB - Complications after implantation of articulated Palmaz-Schatz stents in coronary arteries of 3 patients are reported. In 1 patient, embolization of the stent occurred during the acute phase, and in the other 2 patients, we observed restenosis after 4 and 5 months, respectively. Late restenosis was located in the midportion and the distal end of the stent in 1 patient. In the other patient a severe subtotal occlusion was found 1 cm proximal to the stent. These findings suggest that adaptation of the stent delivery system is needed to prevent loss of the stent and scraping of the vessel wall. PMID- 1611632 TI - Preload-dependent hemodynamic effects of milrinone in moderate heart failure. AB - Milrinone, a bipyridine derivative with positive inotropic and balanced type vasodilating properties, acutely improves cardiac pump function in patients with severe and moderate to severe heart failure. Whether it has similar effects in patients with mild to moderate heart failure is unknown. A hemodynamic evaluation of oral milrinone in dosage of 2.5, 5 and 10 mg was carried out on 3 consecutive days in 18 patients with NYHA class 2.7 heart failure. Patients continued with diuretics and digitalis, administered 15 h before each hemodynamic study. Peak milrinone plasma levels ranged from 77 to 252 micrograms/ml and were attained at 60-90 min following administration. Concomitantly, milrinone significantly reduced pulmonary wedge and right atrial pressures with 24, 47 and 44, and 25, 42 and 38% with the 2.5-, 5- and 10-mg doses, respectively. Milrinone had no effect on cardiac or stroke indices with either dose. Moreover, systemic vascular resistance only decreased by 12% with the highest dose, together with a 7% fall in mean arterial pressure and a 13% rise in heart rate (all p less than 0.05 vs. baseline). Patients were subsequently grouped depending on baseline pulmonary wedge pressure greater than or equal to 18 mm Hg (Gr I, n = 9) or less than 18 mm Hg (Gr II, n = 9). Changes in pulmonary wedge, pulmonary artery and right atrial pressure were similar in both groups following each dose. In contrast, the effect on cardiac pump function clearly differed in patients with high versus normal baseline wedge pressure. In Gr I, cardiac index increased significantly by 16% (5 and 10 mg). In Gr II, cardiac index decreased with 13% following the 10-mg dose (p less than 0.05 vs. baseline). When maximal individual changes in cardiac index were compared, 10 mg milrinone resulted in an improvement of cardiac index in all patients with baseline wedge pressures greater than 15 mm Hg, but in a decrease in cardiac index in patients with lower wedge pressures. It is concluded that milrinone induces contrasting effects on cardiac pump function in patients with mild to moderate heart failure, which may negatively affect its early and, possibly, also late efficacy in this patient group. PMID- 1611633 TI - Risk stratification in suspected acute myocardial infarction based on a sensitive immunoassay for serum creatine kinase isoenzyme MB. A 2.5-year follow-up study in 156 consecutive patients. AB - This prospective study was an evolution of a new sensitive creatine kinase (CK) isoenzyme MB immunoassay in 156 patients, admitted consecutively to the coronary care unit, suspected of having acute myocardial infarction (MI), with regard to clinical applicability and clinical outcome. 42% of the patients had MI based on WHO criteria. The remaining 91 patients could be divided into a group with ischemic heart disease (IHD) without MI being present (n = 65) and a group with non-IHD (n = 26). In the former, a subgrouping based on changing CK MB levels (n = 24) or stable CK MB levels (n = 41) as compared to the non-IHD group could be performed. These patients were not diagnosed using the routine diagnostic procedures. Follow-up was carried out for 30 months (median 22). The prognosis as evaluated by cardiac death was significantly better for patients with stable CK MB levels than for those with changing CK MB levels, inasmuch as the cumulative probability not to suffer cardiac death was 95 +/- 3 and 66 +/- 10% after 2.5 years, respectively (p less than 0.003). It was 52 +/- 6% for the patients with MI, similar to patients with changing CK MB levels (p = 0.15). We conclude that this new CK MB assay can detect a subgroup of patients with IHD, which is not diagnosed using routine diagnostic procedures, with a poor clinical outcome. PMID- 1611635 TI - Anticardiolipin antibody and stroke: possible relation of valvular heart disease and embolic events. PMID- 1611634 TI - Rheumatic heart disease prevalence among schoolchildren of an Ethiopian rural town. AB - Rheumatic heart disease (RHD) is the most important cardiovascular disease in hospital practice in Ethiopia. However, the prevalence rate of RHD at the community level remains unknown. The current survey was undertaken to estimate its prevalence among schoolchildren of a central Ethiopian rural town (Butajira). Accordingly, 92.8% of the entire schoolchildren (n = 3.235) in the town were screened. Their mean age was 13.4 +/- 3.5 years. Fifteen children, accounting for a rate of 4.6/1,000, were noted to have findings consistent with RHD. Females and older children were more frequently affected. Only 2 of the 15 students were aware of their disease, and neither of them were on regular secondary prophylaxis. Our finding is consistent with the hospital-based reports that showed RHD to be a common disorder in clinical practice. At the same time, the lack of awareness about their disease noted among the cases is worrisome and deserves serious attention. PMID- 1611636 TI - Percutaneous balloon mitral valvuloplasty in patients with left atrial thrombi. PMID- 1611637 TI - Effect of propranolol and disopyramide on left ventricular function at rest and during exercise in hypertrophic cardiomyopathy. AB - In 19 patients with hypertrophic cardiomyopathy (15 males, 4 females, mean age 49.2 +/- 10.8 years) left ventricular function was studied with radionuclide ventriculography at rest and during exercise in a crossover design without intervention and after disopyramide and propranolol treatment. 15 of the 19 patients had a resting or latent intraventricular gradient of more than 30 mm Hg. Left ventricular function at rest and during exercise was evaluated before medication, 90 min after oral administration of 200 mg disopyramide or 160 mg propranolol and after 3 weeks of oral therapy with disopyramide 200 mg 2 times a day or propranolol 80 mg 4 times a day. After long-term treatment with disopyramide, resting ejection fraction decreased from 72 +/- 12 to 69 +/- 14% (p less than 0.01) and peak ejection rate (PER) decreased from 3.46 +/- 135 to 3.24 +/- 65 end-diastolic volume (EDV).s-1 (p less than 0.01). Peak filling rate (PFR) at rest decreased from 3.01 +/- 0.8 to 2.77 +/- 0.63 EDV.s-1 (p less than 0.05). Time to peak filling rate (TPFR) at rest and during exercise after acute and chronic therapy did not change compared to control values. Acute and long-term administration of propranolol lead to a significant reduction in heart rate at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611638 TI - Detection of massive pulmonary embolism by transesophageal echocardiography. AB - Transesophageal echocardiography is a new echocardiographic technique with indications that are still expanding and being redefined. Recently, the usefulness of transesophageal echocardiography in pulmonary embolism has been demonstrated in several case reports. In this article, we present 3 cases with pulmonary embolism diagnosed by transesophageal echocardiography and discuss its diagnostic value in this clinical setting. PMID- 1611639 TI - Multicenter evaluation of the efficacy and safety of sustained-release diltiazem hydrochloride for the treatment of hypertension. AB - In a double-blind study, patients with mild-to-moderate hypertension were randomly assigned to receive placebo or increasing daily doses of a new sustained release formulation of diltiazem: 180 mg, 360 mg, and 540 mg, each once daily for two weeks. The numbers of evaluable patients were 26 in the placebo group and 81 in the diltiazem group at week 2, 24 and 75 at week 4, and 23 and 65 at week 6. Changes from baseline in mean supine trough (before drug administration) systolic/diastolic blood pressures were +1.3/-2.7 mmHg after placebo and -4.7/ 6.1 mmHg after diltiazem at week 2; -0.1/-1.7 mmHg after placebo and -7.2/-9.3 mmHg after diltiazem at week 4; and +0.4/-1.7 mmHg after placebo and -6.7/-10.2 mmHg after diltiazem at week 6. The changes were significantly greater after diltiazem than placebo. Increasing the daily dose of diltiazem from 360 mg to 540 mg produced more than proportional increases in mean plasma diltiazem concentrations but only minimal further reductions in blood pressure. Similar rates of adverse experiences were reported by the diltiazem-treated and placebo patients. Treatment was withdrawn in two diltiazem-treated patients because of abnormal electrocardiographic (ECG) changes that were considered to be related to the drug: elevated ST segment in one and first-degree atrioventricular block in the other. No other treatment-related ECG changes were noted. It is concluded that this new once-daily formulation of diltiazem is safe and effective in the treatment of mild-to-moderate hypertension. PMID- 1611640 TI - Steady-state dose proportionality of a once-a-day sustained-release diltiazem hydrochloride formulation in healthy subjects. AB - In this open-label, randomized, cross-over study, 12 healthy subjects received four doses of a new sustained-release formulation of diltiazem hydrochloride for six consecutive days. Blood samples were drawn on days 5 and 6 for determination of plasma diltiazem and desacetyldiltiazem levels. The peak concentrations after 120, 240, 360, and 480 mg of diltiazem were 48.1, 112.6, 180.9, and 276.8 ng/ml, respectively, while the mean minimum concentrations were 6.3, 14.6, 24.9, and 44.6 ng/ml. The areas under the concentration-time curves were 702, 1,642, 2,622, and 4,004 ng.hr/ml. Prolonged, continuous absorption of diltiazem was noted over the 24-hour dosing period. The dose-adjusted mean steady-state plasma diltiazem levels after the four doses were significantly different, consistent with diltiazem's nonlinear absorption, but the plasma profiles were similar, indicating that the diltiazem release rate was not dose-dependent. Therapeutic plasma diltiazem levels (greater than or equal to 40 ng/ml) were maintained for 24 hours after the three larger doses. The changes in the pharmacokinetics of desacetyldiltiazem over the four diltiazem doses were similar to those of diltiazem. The number of adverse treatment experiences tended to increase with the higher doses, but none were severe. The results indicate that, according to their pharmacokinetic profiles, doses of 240 mg to 480 mg of diltiazem are suitable for once-daily administration. PMID- 1611641 TI - Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute purulent bacterial bronchitis. AB - In this single-blind study, 488 patients with acute bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for seven days. Treatment efficacy was evaluated in 98 patients treated with loracarbef and in 99 treated with amoxicillin-clavulanate in whom pretreatment positive cultures of pathogens susceptible to both study drugs were found. Streptococcus pneumoniae, Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Klebsiella pneumoniae were isolated in pure or mixed cultures in 64% of the evaluable patients; S pneumoniae was found in 26%. Among the evaluable patients, the rate of favorable clinical responses (cure and improvement) in the loracarbef group (96 of 98 patients; 98.0%) was similar to that in the amoxicillin/clavulanate group (96 of 99 patients; 97.0%); the favorable bacteriologic response rates were also similar (93.7% vs 92.9%, respectively). Eight patients in the loracarbef group and nine in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were presumed to be drug related in five of the loracarbef group and in seven of the amoxicillin/clavulanate group. During therapy, diarrhea was the most frequently reported event in both groups. However, it occurred in only 8.2% of the loracarbef-treated patients compared with 22.5% of the amoxicillin/clavulanate patients (P less than 0.001). It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute purulent bacterial bronchitis. PMID- 1611642 TI - Efficacy of erythromycin in the treatment of inner city pregnant women with cervical Chlamydia trachomatis infection. AB - In this retrospective study, the efficacy of screening for and treating cervical Chlamydia trachomatis infection was evaluated in a pregnant population at increased risk for chlamydial infection. Over a 2 1/2-year period, 5.75% (338) of the 5,875 women tested were found to be infected with this organism. Of the 323 women patients available for follow-up, 76% (244) were successfully treated and 24% (79) remained infected throughout their pregnancies. Forty (12%) patients became infected during pregnancy, while 26 (8%) were reinfected during pregnancy, despite treatment with erythromycin. Twenty-seven (8%) patients had their first antenatal visit and cervical swab less than a week before delivery. The gestational age at which the first cervical chlamydial swab was obtained was significantly more advanced in patients who remained infected (30.23 +/- 6.2 weeks) than those who were successfully treated (22.15 +/- 7.66 weeks; P = 0.00001). The data suggest that in a pregnant population considered to be at increased risk for C trachomatis infection: (1) there is a subgroup of patients with a high risk of remaining infected or becoming reinfected with C trachomatis during pregnancy despite treatment with erythromycin and (2) repeated prenatal testing and treatment of those infected is necessary to detect and eradicate maternal chlamydial infection. PMID- 1611643 TI - Comparative sorption of clomipramine, viloxazine, and maprotiline hydrochlorides in polyvinylchloride bags and glass vials. AB - The sorption of clomipramine, viloxazine, and maprotiline hydrochlorides was studied comparatively in polyvinylchloride (PVC) bags and glass flasks for up to 72 hours. When stored in glass flasks, no decrease in concentration was observed for any of the three drugs, either in dextrose or sodium chloride isotonic solution. When stored in PVC bags, a slight loss (about 7% within 72 hours), was noted for clomipramine hydrochloride in both isotonic solutions, but not for the other two drugs. PMID- 1611644 TI - Glyburide in non-insulin-dependent diabetes: an update. AB - Recent data suggest that non-insulin-dependent diabetes mellitus (NIDDM) may evolve in genetically predisposed individuals beginning with impaired peripheral glucose metabolism followed by insulin deficiency. Glyburide is an effective, long-acting, second-generation oral sulfonylurea introduced in the United States in 1984. In comparison with the first-generation sulfonylureas, glyburide is at least as effective, has a lower incidence of side effects, and may enhance postreceptor insulin activity to a greater degree. Glyburide can improve glycemic control, as evidenced by reduced fasting blood glucose concentrations and glycohemoglobin levels, without the inconvenience of insulin injections, the higher plasma insulin concentrations, and the additional training required to administer insulin. Because of its ability to enhance target tissue insulin action, glyburide also improves glycemic control in many NIDDM patients who have previously failed therapy with other sulfonylurea agents. Gluburide, as adjunctive therapy, may reduce the daily dosage needed by those who require insulin. Favorable pharmacokinetics and high inherent potency of glyburide often allow effective therapy when the drug is administered once a day. PMID- 1611646 TI - Tolerance of a soy formula by infants and children. AB - For a minimum of one month (mean, 54 days), 287 infants and children less than 8 years of age were fed an isolated soy-protein formula. Prior to entry into the study, a cow's milk formula was being fed to 71%, a soy formula to 9%, and cow's milk or other formulas to 20%. Intolerance to cow's milk was reported in 35% of the patients, symptoms indicative of cow's milk intolerance in 23%, diarrhea or gastroenteritis in 18%, a family history of allergy in 13%, and insufficient weight gain, intolerance to other formulas, or constipation in 11%. The patients showed normal increases in weight and length during the study. A significant decrease in the following symptoms were reported in the patients from before to after treatment: abdominal cramps, bloating or gas, colic, diarrhea, fussiness, rashes or eczema, spitting up, waking up crying at night, wheezing, and vomiting. It is concluded that, while receiving soy formula, infants and children continued to thrive normally and that the formula was well tolerated. After receiving soy formula, the frequency of undesirable feeding-related symptoms was reduced in the majority of infants and children. PMID- 1611645 TI - Loracarbef (LY163892) versus amoxicillin/clavulanate in the treatment of acute bacterial exacerbations of chronic bronchitis. AB - In this single-blind study, 579 patients with chronic bronchitis were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate thrice daily for seven days. Treatment efficacy was evaluated in 129 of the loracarbef-treated patients and 120 amoxicillin/clavulanate-treated patients in whom pretreatment positive cultures of pathogens susceptible to both antibiotics were isolated. Three organisms predominated in either pure or mixed cultures in 57.0% of the evaluable patients: Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella (Branhamella) catarrhalis; H influenzae was isolated in 25.0% of the patients with single pathogens. Among the evaluable patients, favorable clinical responses (cure or improvement) were noted in 93.8% of the loracarbef-treated patients and in 95.0% of the amoxicillin/clavulanate-treated patients. A favorable bacteriologic response (pathogen eliminated or presumed eliminated) was found in 82.2% of loracarbef-treated patients and 90.0% of amoxicillin/clavulanate-treated patients. Six patients in the loracarbef group and 14 in the amoxicillin/clavulanate group discontinued treatment because of adverse events. The events were judged to be drug related in four loracarbef-treated patients and in 11 amoxicillin/clavulanate-treated patients. The incidence of diarrhea and other gastrointestinal symptoms was significantly more frequent in the amoxicillin/clavulanate group (13.5% and 5.6%) than in the loracarbef group (4.5% and 1.7%), while the incidence of severe headaches was significantly more frequent in the loracarbef than the amoxicillin/clavulanate group (7.2% vs 3.1%). It is concluded that loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial exacerbations of chronic bronchitis. PMID- 1611647 TI - Tolerance of a milk-based formula by infants. AB - A standard, low-iron, milk-based formula was fed to 781 healthy infants younger than 12 months of age. The infants showed normal increases in weight and length during the study. The formula was well tolerated by most of the infants. The most frequently reported symptoms of intolerance before and during the study were loose stools (in 78%) and spitting up (in 79%). A significant decrease from before to after the study was reported in the symptoms of colic, constipation, diarrhea, loose stools, skin rashes, and spitting up. It is concluded that a standard milk-based formula is well tolerated by most healthy infants. PMID- 1611648 TI - Loracarbef (LY163892) versus amoxicillin/clavulanate in bronchopneumonia and lobar pneumonia. AB - In a single-blind study, 134 patients with bronchopneumonia or lobar pneumonia were randomly assigned to receive 400 mg of loracarbef twice daily or 500/125 mg of amoxicillin/clavulanate three times daily for 10 to 14 days. Treatment efficacy was evaluated in 38 patients treated with loracarbef and in 39 treated with amoxicillin/clavulanate in whom pre-treatment positive cultures of pathogens susceptibile to the study drugs were isolated. Streptococcus pneumoniae and Haemophilus influenzae were cultured as single pathogens in 40.3% of the evaluable patients. Among the evaluable patients, 100% of the loracarbef group and 92.3% of the amoxicillin/clavulanate group had a favorable clinical response (cure or improvement). Bacteriologic response was favorable and the pathogen was eliminated or presumed eliminated in 97.4% of the loracarbef-treated patients and in 92.3% of the amoxicillin/clavulanate-treated patients. Treatment was discontinued in one loracarbef-treated patient because Ludwig's angina, unrelated to the study drug, was diagnosed and in five amoxicillin/clavulanate-treated patients because of diarrhea (two patients), rash (two patients), and nausea and vomiting (one patient). Diarrhea, the most frequently cited adverse event, was reported by 6.1% of the loracarbef-treated patients and 11.8% of the amoxicillin/clavulanate-treated patients. Asthenia was reported by 0% and 8.8% of the loracarbef and amoxicillin/clavulanate patients, respectively. It is concluded that both loracarbef and amoxicillin/clavulanate are safe and effective in the treatment of acute bacterial pneumonia. PMID- 1611649 TI - Comparison of the short-term efficacy and tolerability of lovastatin and pravastatin in the management of primary hypercholesterolemia. AB - Few data are available on the relative efficacy and tolerability of lovastatin and pravastatin, two 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, currently available in North America for treatment of hypercholesterolemia. The recommended starting dose is 20 mg QD with the evening meal for lovastatin. The recommended starting dose is 10 mg or 20 mg once daily at bedtime for pravastatin. In a double blind, double placebo, multicenter, randomized study, we compared the changes in plasma lipids and apolipoproteins in 217 patients with primary hypercholesterolemia treated for eight weeks with lovastatin 20 mg QD to pravastatin 10 mg QD or pravastatin 20 mg QD. The reductions in total cholesterol (TC) (21%), low-density lipoprotein cholesterol (LDL-C) (28%), and apolipoprotein B (apo B) (22%) were comparable for the lovastatin 20-mg and pravastatin 20-mg groups. Lovastatin 20 mg QD was significantly more effective than pravastatin 10 mg QD in lowering TC and LDL-C after four weeks of therapy and in the reduction of apo B after four and eight weeks of therapy. At the end of eight weeks of therapy, the mean reductions in TC and LDL-C were numerically greater with lovastatin 20 mg QD compared with pravastatin 10 mg QD, but the differences were not statistically significant. At the end of eight weeks, there was no difference between pravastatin 20 mg and pravastatin 10 mg in lowering TC and LDL-C. The frequency of overall side effects, including central nervous system-related symptoms and headache, was similar and low in all groups. PMID- 1611650 TI - Flumazenil and seizures: analysis of 43 cases. AB - Flumazenil is a new drug indicated for the reversal of the sedative effects of benzodiazepines mediated at the benzodiazepine-receptor site. Worldwide sources to date have disclosed 43 cases of seizures related, at least temporally, to the intravenous administration of flumazenil. There was no apparent relationship between the dose of flumazenil and the development of seizures, which occurred at doses ranging from 0.2 to 10.0 mg. The seizures were not considered to be a toxic effect of flumazenil, but many of them probably were due to an unmasking of the anticonvulsant effect of the previously used benzodiazepine or to a severe benzodiazepine-withdrawal syndrome. Eighteen (42%) of the patients had ingested overdoses of cyclic antidepressants, which were considered responsible for the seizures. In addition to patients with concurrent cyclic antidepressant poisoning, high-risk populations include patients who have been treated with benzodiazepines for a seizure disorder or an acute convulsive episode, patients with concurrent major sedative-hypnotic drug withdrawal, patients who have recently been treated with repeated doses of parenteral benzodiazepines, and overdose patients with myoclonic jerking or seizure activity before flumazenil administration. To minimize the likelihood of a seizure, it is recommended that flumazenil not be administered to patients who have used benzodiazepines for the treatment of seizure disorders or to patients who have ingested drugs (eg, cyclic antidepressants, cocaine, lithium, methylxanthines, isoniazid, propoxyphene, monoamine oxidase inhibitors, buproprion HCl, and cyclosporine) that place them at risk for the development of seizures. PMID- 1611651 TI - A noncomparative study of cefprozil at two dose levels in the treatment of acute uncomplicated bacterial sinusitis. AB - The efficacy and safety of cefprozil at two dose levels were evaluated in 110 patients with acute uncomplicated bacterial sinusitis in an uncontrolled, noncomparative, Phase II trial. Ninety patients received 250 mg of cefprozil (low dose group) and 20 patients received 500 mg of cefprozil (high-dose group) every 12 hours for ten days. Evaluable patients had symptoms consistent with acute sinusitis, pathogens isolated at pretreatment susceptible to cefprozil, and a radiograph positive for sinusitis within 48 hours before treatment. A satisfactory clinical response was achieved in 34 of 39 evaluable patients (87%) in the low-dose group and in all 16 evaluable patients (100%) in the high-dose group. Pathogens were eradicated in 35 of 39 patients (90%) in the low-dose group and in 15 of 16 patients (94%) in the high-dose group. A total of 140 of 155 pathogens (90%) isolated pretreatment were susceptible to cefprozil. Six patients (7%) in the low-dose group and one patient (5%) in the high-dose group reported at least one adverse clinical event. PMID- 1611653 TI - Milestones in clinical pharmacology. Clinical relevance of pharmacogenetics rediscovered. PMID- 1611654 TI - An analysis of miniature synaptic events recorded from locust muscle--variations in amplitude and time courses. AB - A study of miniature post-synaptic potentials (min. e.p.s.p.'s) in metathoracic extensor tibiae muscle fibres at neuromuscular junctions of adult locusts (Schistocerca gregaria) has been undertaken. Extracellular min. e.p.s.p.'s recorded from single junctional sites and their "marked" intracellular min. e.p.s.p. counterparts varied both in time course and amplitude and at many sites a small proportion of abnormal miniatures were observed, i.e., of large amplitude and/or of long duration. Positive correlations between the rise times and 1/2 decay times of the extracellular min. e.p.s.p.'s and between rise times and amplitudes and 1/2-decay times and amplitudes of "marked" intracellular events were found. Comparison of results obtained from differently innervated muscle fibres demonstrates that the occurrence of abnormal miniatures is independent of the type of innervation i.e., "fast" or "slow" excitatory motoneurons. Mechanisms that lead to the occurrence of abnormal miniatures are discussed in relation to the presence of large vesicles in the terminals of the excitatory motoneurons but the occurrence of these events could equally well be explained by the "post synaptic saturation hypothesis". PMID- 1611652 TI - Cefprozil versus cefaclor in the treatment of acute and uncomplicated urinary tract infections. Cefprozil Multicenter Study Group. AB - Cefprozil is a new oral cephalosporin with an in vitro spectrum of activity that includes the pathogens most commonly associated with acute and uncomplicated urinary tract infections (UTIs). A multicenter, randomized study was conducted to compare the clinical efficacy and safety of cefprozil, administered once daily, with cefaclor, administered three times a day, for ten days in patients 2 years of age or older who had acute and uncomplicated UTIs. The rate of satisfactory clinical response in evaluable patients was 87% in the cefprozil group and 84% in the cefaclor group. The patient bacteriologic response rates were also similar: 83% for cefprozil and 85% for cefaclor. The overall effective response rate for both cefprozil and cefaclor was 77%. Both drugs were well tolerated, with no difference in the incidence of drug-related adverse events. Because of its efficacy and once-daily dosing regimen, cefprozil may be an alternative to currently available oral antibiotics in the treatment of UTIs. PMID- 1611655 TI - Expression of sucrase-isomaltase mRNA along the villus-crypt axis in the rat small intestine. AB - Sucrase-isomaltase has been used as a marker enzyme to study cell differentiation along the intestinal villus-crypt axis. Previous studies are in agreement that sucrase activity is confined to villus epithelial cells. However, immunoreactivity data are at conflict, with some studies reporting sucrase antigen in crypts as well as villi. To resolve this discrepancy, our goal was to determine the distribution of sucrase-isomaltase mRNA. A cDNA clone representing 3.0 kb of rat sucrase-isomaltase, including the sucrase active site, was characterized. Northern analysis of 12 tissues demonstrated a 6 kb transcript only in the small intestine. Jejunal cell fractions prepared by a washing technique showed declining levels of both sucrase activity and sucrase-isomaltase mRNA as well as increasing levels of thymidine kinase activity from early to later fractions. Since later fractions did not yield pure crypt cells, in situ hybridization using an 35S-labeled sucrase-isomaltase riboprobe was performed. The transition from zero to intense signal at the crypt-villus junction leads us to conclude that in the adult rat, sucrase-isomaltase gene expression is initiated only after cells leave the proliferative cycle and migrate onto the villi. PMID- 1611656 TI - The distribution of neuropeptide Y-like immunoreactivity in the ascidian Styela plicata. AB - The occurrence of neuropeptide Y-like substances has been verified in the nervous system and alimentary tract of the ascidian Styela plicata. Neuropeptide Y-like immunoreactivity is present in a few small neurons and in a network of beaded nerve fibres of the cerebral ganglion. Neuropeptide Y-like immunoreactive material can be also localized in the endostyle and in a few cell bodies of the branchial walls. Moreover, immunofluorescent endocrine-like cells of the "open" type occur in the gastric folds. Finally, some possible functions of the ascidian neuropeptide Y are discussed. PMID- 1611657 TI - Radioautographic study on DNA synthesis of the retina and retinal pigment epithelium of developing mouse embryos. AB - We report the changes of proliferative activity of the retina and retinal pigment epithelium (RPE) of mouse embryos by detecting cells in the S-phase by light microscopic radioautography using 3H-thymidine. The eyes germs of mouse embryos at the embryonic days 9.5 (E 9.5), E 11.5, E 13.0, E 15.5, E 18.5 of gestational ages, were used for this experiment. Small pieces of the ocular tissues were labelled with 3H-TDR in vitro and light microscopic radioautographs were prepared. The labeling indices of the respective regions of tissues were calculated. Both tissues of retina and RPE showed high percentages of labeling indices from 10% to 50% through the developmental stages. The labeling indices of both tissues in earlier stages were generally higher than those of later stages, and gradually decreased in the later stages. However, the retina and RPE showed different courses of the changes of labeling indices respectively during the embryonic development. In the retina, the labeling indices in the vitreal portions were more than those in the scleral portions during the earlier developmental stages. However, in the later stages, the indices of scleral portions were more than those in the vitreal portions. Comparing the three regions of retina, the labeling indices of the anterior regions were generally higher than those of the equatorial and posterior regions, especially in the vitreal portion. Remarkable differences among three regions were not found in the scleral portion. In the RPE, the labeling indices gradually increased in the anterior region, but decreased in the equatorial and the posterior regions through all the developmental stages. The proliferation of both retina and RPE in the central region occurred earlier than those of the peripheral region. PMID- 1611658 TI - Effect of epidermal growth factor on ornithine decarboxylase activity and urea synthesis in isolated rat hepatocytes. AB - Ornithine decarboxylase (ODC) activity is induced by protein-synthesis independent mechanisms in freshly isolated rat hepatocytes, incubated either without or with a mixture of amino acids in the incubation medium. Urea synthesis rates were two- to three-fold higher in those hepatocytes incubated in the presence of amino acids that in those lacking amino acids in the medium. Epidermal growth factor (EGF) delayed ODC induction, but only in the presence of amino acids. EGF significantly decreased ureagenesis when hepatocytes were incubated in the presence of amino acids and only endogenous substrates were available. No evidence of any link between ODC induction and urea synthesis was found. PMID- 1611659 TI - Molecular and biochemical study of the presence and synthesis sites of methionine enkephalin-like substances in the circumoesophageal ganglia, the ovotestis and the tentacles of the snail. AB - In situ hybridization with an oligonucleotidic 35S-labelled probe complementary to the 388-435 coding region of rat proenkephalin mRNA seems to show a colocalization between synthesis and storage sites of methionine-enkephalin(MK) like substances only in young cellular stages of the ovotestis and in several neurons of cerebral, parietal and pleural ganglia. No positive signal can be detected neither in pedal and visceral ganglia nor in the tentacular collar cells, in spite of previous immunocytochemical data. Radioimmunoassays carried out on acidic extracts of the same organs confirm the molecular results and lead us to conclude to the presence of substances strongly related to MK in the ovotestis as well as in the circumoesophageal ganglia (COG), and to ascertain that the MK-positive tentacular collar cells do not contain authentic MK. PMID- 1611660 TI - New specific markers of human and mouse fibroblasts. AB - The expression of different lineage-specific markers was examined on tissue derived fibroblast cultures in three species (mouse, rat and human), using indirect immunofluorescence or labelled streptavidin-biotin techniques. Smooth muscle cells and a human monocyte-like cell line (U 937) were used as controls. Five monoclonal antibodies against human fibroblast epitopes et two against mouse fibroblasts were selected during this screening on cell cultures. Three surface markers (Thy-1, 6-19 and 1B10) and, particularly, one (5B5) cytoplasmic marker of human fibroblasts were suitable for labeling frozen, but not paraffin-embedded, tissue sections. Unfortunately, the two mouse fibroblast markers appeared of difficult and limited interest for this histopathologic strategy. PMID- 1611661 TI - Aging of human erythrocytes: the role of membrane perturbations induced by in vitro ATP-depletion. AB - The in vitro metabolic depletion of the erythrocytes has been often utilized to mimic the oxidative stress responsible of their in vivo senescence process. The present study is focused to detect the extent to which the modifications of the whole cell and/or of its membrane, consequent to in vitro ATP-depletion, could trigger a mechanism similar to that verified during in vivo aging. From our data it appears that the shape changes and the increased osmotic fragility could be related to physico-chemical alterations that take place at membrane level. Main alterations concern the significant decrease of negative charges of membrane surface, as evidenced by fluorescence intensity enhancement of membrane associated ANS, and of the increase of fluidity in the lipid/protein membrane region, suggesting a close analogy with the progressive in vivo senescence of the RBC. Furthermore, the ATP-depletion erythrocyte can efficiently remove exogenous hydrogen peroxide differently from old RBC that showed, as well reported, a severe decrease of enzymic protection against oxidative insult. PMID- 1611662 TI - Characterization of cellular and molecular immune effectors against Trichinella spiralis newborn larvae in vivo. AB - The cellular and molecular immune effectors that participated in host immunity against Trichinella spiralis newborn larvae were characterized in vivo using AO rats. Donor rats were immunized with 2,000 muscle larvae orally or 11,400 newborn larvae i.v. Immune serum and cells from spleen, peripheral lymph nodes, mesenteric lymph node, thoracic duct lymph and the peritoneal cavity were obtained from donor rats 10-21 days after infection and transferred into normal recipient rats. The control recipients received either no cells and serum or normal cells and normal serum obtained from normal donors. Newborn larvae (20,000 50,000) were injected either i.v. or ip into these recipients and immunity against newborn larvae was measured either by muscle larvae burden of the recipients three weeks later or by direct recovery of newborn larvae from the peritoneal cavity of the recipients. The experiments demonstrated that immune lymphocytes conferred no protection in the recipients but that immune serum and immune peritoneal cells were protective and these effects were synergistic. Cell adherence to the cuticle and killing of newborn larvae were observed in the peritoneal cavity of immune rats. Positive fluorescence was observed on newborn larvae incubated with fractionated IgM and IgG(E) antibody isotypes. Massive deposition of antibody molecules on newborn larvae was demonstrated by scanning electron microscopy. Studies using transmission electron microscopy revealed that the larval adherent cells were stimulated macrophages, neutrophils and eosinophils. PMID- 1611663 TI - Morphological comparison by scanning electron microscopy of transient retina muscle synapses and long-lived spinal cord-muscle synapses. AB - Retinal neurons will form cholinergic synapses on muscle cells in tissue culture, however, these inappropriate synapses are transient. Although within 24 hrs. myotubes are readily innervated, by 7 days of coculture no physiological response can be detected. In contrast, spinal cord neurons form long-lived synapses on muscle cells which can be detected for several weeks. In this study, we examined retina-muscle and spinal cord-muscle cocultures to determine whether retinal neurons withdrew their processes from muscle cells, and preferentially maintained contacts on other retinal neurons. Using scanning electron microscopy, we observed that during the first 24 hrs. of coculture both types of neurons extend processes along myotubes. The neurite outgrowth occurs concomitantly with the observed increase in physiologically detected synaptic muscle responses. Over the next 6 days, retinal neurite contacts on the muscle cells are withdrawn, while spinal cord contacts remain. Retinal neurons remain in contact with other retinal neurons at day 7 of coculture. Thus, retinal neurons form and maintain synapses on their appropriate target (other retinal neurons); whereas, they withdraw contacts from inappropriate targets (muscle cells). By contrasting retinal and spinal cord synapses on muscle cells, we hope to elucidate the mechanisms of synaptic recognition and maintenance. PMID- 1611664 TI - Filipin labeling in Chlamydomonas gametes exposes site-specific lipid specializations. AB - A thin section study of mating Chlamydomonas cell wall-less CW 15 mating type plus (mt+) and mating type minus (mt-) gametes utilized filipin. The results show extensive labeling of mt+ and mt- plasma membranes. No labeling was seen on the mating structure membranes of activated mt+ or mt- gametes. These results indicate that differences exist between the plasma membrane and the mating structure membrane of gametes. If filipin is specific for the 3-beta-OH sterol, ergosterol and/or other Chlamydomonas sterols, then these results imply that the fusing mating structure membranes may be altered or reduced in sterol content. Such lipid specializations may increase local membrane fluidity and thereby facilitate the site-specific cell fusion associated with mating Chlamydomonas gametes. PMID- 1611665 TI - Analysis of the chromosomal DNA polymorphism of wine strains of Saccharomyces cerevisiae. AB - Wine yeast strains are characterized by a high chromosomal DNA polymorphism. This can be explained partly by a size difference of different variants of specific chromosomes. This difference can reach up to 45% of the size of the chromosome in question. Two strains, SB1 and Eg8, have a very complex chromosomal pattern and show one band hybridizing with probes from two different chromosomes derived from a reference strain. This is an indication of the presence of "hybrid" chromosomes in these wine strains. The most astonishing result concerns chromosome VIII, frequently present in wine strains in two variant forms. The first normal form has a size of about 580 kb while the second is around 1000 kb. These two forms segregate at meiosis and recombine with a normal chromosome VIII from a laboratory strain. Wine yeasts are thus very different from haploid laboratory strains. PMID- 1611666 TI - Adaptation and major chromosomal changes in populations of Saccharomyces cerevisiae. AB - Thirteen independent populations of Saccharomyces cerevisiae (nine haploid and four diploid) were maintained in continuous culture for up to approximately 1000 generations, with growth limited by the concentration of organic phosphates in medium buffered at pH 6. Analysis of clones isolated from these populations showed that a number (17) of large-scale chromosomal-length variants and rearrangements were present in the populations at their termination. Nine of the 16 yeast chromosomes were involved in such changes. Few of the changes could be explained by copy-number increases in the structural loci for acid phosphatase. Several considerations concerning the nature and frequency of the chromosome length variants observed lead us to conclude that they are selectively advantageous. PMID- 1611667 TI - Isolation and characterization of the Aspergillus niger pyruvate kinase gene. AB - The Aspergillus niger gene encoding pyruvate kinase was cloned by heterologous hybridization using a fragment from the corresponding yeast gene as a probe. The primary structure of the gene, including 5' and 3' flanking sequences, was determined. The structural part of the A. niger pkiA gene is 2054 bp long and is interrupted by seven putative introns. Splicing of the intron sequences results in an open reading frame of 1578 bp, encoding a protein of 526 amino-acid residues and a molecular weight of 58,130 Da. Extensive homology is found with pyruvate kinase from A. nidulans; only 33 amino acids are different between both proteins. Transformation experiments using the pyrA gene as a selection marker and the subcloned pkiA gene as a co-transforming marker led to increased levels of pyruvate kinase. Analysis of the transformants showed that in none of the transformants integration had occurred at the pkiA locus. Predominantly co integration of the pyrA- and the pkiA-containing plasmids was found in the cases examined. PMID- 1611668 TI - Recovery of recombinant plasmids from Pleurotus ostreatus transformants. AB - A transformation system employing selectable resistance to hygromycin B has been developed for the mushroom-forming fungus, Pleurotus ostreatus. Vector pAN7-1, a commonly used non-replicative vector for integrative transformation in fungi, yielded 5-46 resistant colonies per micrograms of DNA per 10(7) viable protoplasts. Southern blot analysis of certain transformants revealed unexpected replicative plasmids containing pAN7-1 sequences, but modified for size, methylation and restriction enzyme pattern when compared to the initial transforming vector. Two such replicative derivatives of pAN7-1 have been rescued from P. ostreatus by cloning into Escherichia coli. Rescued plasmids have been used to probe DNA from untransformed P. ostreatus in an effort to identify fungal sequences that recombined in vivo with pAN7-1 to form replicative plasmids. Such replicative sequences have been localized in high molecular weight (chromosomal) DNA of wild-type P. ostreatus. Transformation has been obtained for P. ostreatus using a rescued plasmid, thereby confirming the role of this recombinant plasmid as a shuttle vector. PMID- 1611669 TI - Expression of ORF1 of the linear 2.3 kb plasmid of maize mitochondria: product localization and similarities to the 130 kDa protein encoded by the S2 episome. AB - ORF1 of the ubiquitous 2.3 kb linear plasmid of maize mitochondria encodes a 39 kDa protein detected with polyclonal antibodies raised to a beta galactosidase:ORF1 fusion protein. Almost half of this protein is similar to a domain of the 130 kDa protein encoded by the S2 episome of mitochondria from cytoplasmic male-sterile lines. Antisera raised to the ORF1 2.3 kb plasmid product cross-reacts with the ORF1, 130 kDa protein from the S2 episome. Despite the shared domain, the proteins are differentially localized: the 130 kDa protein is membrane-associated while the ORF1 protein is found in the matrix. We discuss possible functions of the ORF1 protein. PMID- 1611670 TI - In vitro mutagenesis of the mitochondrial leucyl-tRNA synthetase of S. cerevisiae reveals residues critical for its in vivo activities. AB - The mitochondrial leucyl-tRNA synthetase (mLRS) of Saccharomyces cerevisiae is involved in both mitochondrial protein synthesis and pre-mRNA splicing. We have created mutations in the regions HIGH, GWD and KMSKS, which are involved in ATP-, amino acid- and tRNA-binding respectively, and which have been conserved in the evolution of group I tRNA synthetases. The mutants GRD and NMSKS have no discernible phenotype. The mutants AWD and ARD act as null alleles and lead to the production of 100% cytoplasmic petites. The mutants HIGN, NIGH and KMSNS are unable to grow on glycerol even in the presence of an intronless mitochondrial genome and accumulate petites to a greater extent than the wild-type but less than 40%. Experiments with an imported bI4 maturase indicate that the lesion in these mutations primarily affects the synthetase and not the splicing functions. PMID- 1611671 TI - Rapid and simple isolation of DNA from agarose gels. AB - We present a simple method for the isolation of DNA from agarose gels that is economic, fast, and independent of electrical equipment. DNA fragments of up to 6 kb can be easily extracted within 5 min using a disposable plastic syringe and filter paper. Total extraction of DNA fragments between 10 and 20 kb in size is achieved by concentrating the DNA flushed from the gel in a DNA-binding column. PMID- 1611672 TI - 6-Azauracil inhibition of GTP biosynthesis in Saccharomyces cerevisiae. AB - The addition of 6-azauracil to the growth medium causes a strong reduction of the GTP level in the nucleotide pool of Saccharomyces cerevisiae. In-vitro experiments show a strong inhibition of IMP dehydrogenase activity by 6-azaUMP explaining the preceding effect. PPR2 mutants, previously characterized by an increased sensitivity to 6-azauracil compared to the wild-type, are specifically susceptible to the lowering of the GTP pool, and are able to grow in presence of 6-azauracil when guanine is added to the medium. PMID- 1611673 TI - Cellular mechanisms of entrainment. AB - This review summarizes our current understanding of the signal transduction cascade by which light causes phase shifts of the circadian oscillators found in the eye of Bulla and Aplysia. The isolated retina of these marine mollusks contains a circadian oscillator, a photoreceptor, and a light transduction pathway sufficient for entrainment. This preparation offers unique advantages for the cellular analysis of entrainment and the generation of circadian oscillations. There is evidence that similar cellular mechanisms may underlie mammalian and molluscan circadian oscillations. Thus, the models developed to explain entrainment in the molluscan retina are likely to have utility in exploring the mammalian suprachiasmatic nucleus. PMID- 1611674 TI - The hunt for mechanisms of circadian timing in the eye of Aplysia. AB - The goals of our research are to understand how circadian oscillations in the eye of Aplysia california are generated and how entraining agents regulate these oscillations. These goals require identification of the molecular components of the oscillator and entrainment pathways as well as elucidation of the biochemical processes by which these components interact with one another. Our experimental strategy entails tracing environmental information along an entrainment pathway until the last component of the pathway is reached. The isolated eye of Aplysia exhibits a circadian rhythm of optic nerve impulses. This rhythm is regulated by at least two entrainment pathways. A photic pathway entrains the rhythm to light dark cycles and an efferent serotonergic pathway relays neural information from the CNS to the oscillator. Phase shifting by light appears to involve an increase in the levels of cGMP, depolarization, and protein synthesis. Phase shifting by serotonin appears to involve an increase in the levels of cAMP, hyperpolarization, and protein synthesis. The involvement of protein synthesis in the entrainment pathways, together with the findings that brief treatments of inhibitors of protein synthesis phase shift the rhythm and that continuous treatments of these inhibitors alter the period of the rhythm, indicates that translation is part of the oscillator mechanism. Recent evidence indicates that transcription may also be part of the oscillator mechanism. Brief treatments with DRB, a reversible transcription inhibitor, phase shift the rhythm while continuous treatments with DRB lengthen the period of the rhythm. A comparison of the effects of transcription and translation inhibitors on the rhythm indicates that transcription and translation are closely coupled in the eye circadian system. To know the precise role of transcription and translation in the circadian system, it is necessary to identify and then study specific proteins and mRNAs important for circadian timing. To identify putative oscillator proteins (POPs), we have hunted for proteins whose synthesis or phosphorylation was altered by the entraining agents light and 5-HT and by other agents that perturb the circadian rhythm. By exposing eyes to labeled amino acids in the presence of phase-shifting treatments and then using two-dimensional gel electrophoresis to separate proteins, we found eight proteins that may be considered POPs. To elucidate the cellular function of POPs, we have begun to obtain their amino acid sequences. A 40,000, pI 5.6 protein (POP-1) was identified as a member of the lipocortin family of proteins. Lipocortins are Ca(2+)-phospholipid binding proteins whose functions include inhibition of PLA2.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611676 TI - Purines. LI. Synthesis and biological activity of hypoxanthine 7-N-oxide and related compounds. AB - A detailed account is given of the first chemical synthesis of hypoxanthine 7-N oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group. The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure. An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H2O mainly as the N(7)-OH tautomer (21). In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC50 of 100 micrograms/ml. It did not show any antimicrobial activity even at 1000 micrograms/ml. None of the 9-(4-methoxybenzyl) (11) and O methyl (12, 13, and 14) derivatives was found to be antileukemic or antimicrobial. PMID- 1611675 TI - Effects of (+)-, (-)- and (+/-)-indenestrols A and B on microtubule polymerization. AB - Indenestrol A (IA) is a metabolite of diethylstilbestrol (DES), and indenestrol B (IB) is an analog of IA. IA was simply obtained from E,E-dienestrol in the presence of dilute sulfuric acid, and a mixture of IA and IB was formed by thermal cyclization of E,E-dienestrol. In order to elucidate the effects of optically active IA and IB on microtubule assembly, the IA and IB enantiomers were separated to greater than 99% purity by high-pressure liquid chromatography using a chiral column. The di(4-bromobenzoate) of (-)-IB was analyzed by X-ray crystallography and its absolute structure was determined as C(3)-S. The (+)-, ( )-, and (+/-)-indenestrols A and B were shown to be inhibitors of microtubule assembly in vitro using microtubule proteins from porcine brain. (+/-)-IB is more active than (+/-)-IA, and the order of inhibitory activity of the enantiomers on microtubule assembly was (+)-IB greater than (+)-IA greater than (-)-IA greater than (-)-IB. PMID- 1611678 TI - Triazole antifungals. V. Synthesis and antifungal activities of some amides related to 3-acylamino-2-aryl-1-triazolyl-2-butanol. AB - Amides, 2 and 3 related to the potent antifungal triazole-amide 3-acylamino-2 aryl-1-triazolyl-butanol(1) were synthesized starting from the triazole-alcohol 6. The antifungal activity of 2 and 3 against a mouse systemic Candida albicans infection was found to be less potent than that of 1. PMID- 1611679 TI - Imidazo[1,2-alpha]pyridines. II. Ozonolysis of imidazo[1,2-alpha]pyridines and synthesis of cardiotonic agents. PMID- 1611677 TI - Synthesis and pharmacology of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives, a new class of potent serotonin-3 (5-HT3) receptor antagonists. AB - A series of 3,4-dihydro-3-oxo-1,4-benzoxazine-8-carboxamide derivatives was synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activity assessed by their ability to antagonize the von Bezold-Jarish (BJ) effect in rats. Derivatives bearing 1-azabicyclo[2.2.2]oct-3-yl moiety as a basic function attached to the carboxamide at position 8 showed more potent antagonistic activity than those bearing the other three basic moieties. Structure-activity relationships of this series showed that methyl and chloro groups were more effective as substituents at positions 4 and 6, respectively. The representative compound 15 (Y-25130) in this series showed potent antagonistic activity on the BJ effect (ED50 = 1.3 micrograms/kg i.v.), high affinity for 5-HT3 receptor (Ki = 2.9 nM) and complete protection against cisplatin-induced emesis in dogs at a dose of 0.1 mg/kg i.v. PMID- 1611680 TI - Antitumor agents. V. Synthesis and antileukemic activity of E-ring-modified (RS) camptothecin analogues. AB - Several E-ring-modified analogues of (RS)-camptothecin were synthesized by total synthesis via Friedlander condensation and evaluated for cytotoxicity and antitumor activity against P388 mouse leukemia cells. Among them, (RS)-20 deoxyamino-7-ethyl-10-methoxycamptothecin (25c) was found to be more active than (RS)-camptothecin (1) in the in vivo assay. PMID- 1611681 TI - High performance liquid chromatography of 99mTc labeled human serum albumin using an N-methylpyridinium polymer column. AB - Human serum albumin (HSA) labeled with 99mTc (99mTc-HSA) was analyzed by high performance liquid chromatography using a 4-vinylpyridinium polymer column which specifically resolved albumin components such as human mercaptalbumin (HMA), human non-mercaptalbumins (HNA), etc. The 99mTc-HSA radiochromatogram revealed that 99mTc-HSA consisted of several components. The radiochromatographic profile was similar to that of 99mTc-HMA prepared with 99mTc and separated HMA. This suggested that HMA participated mainly in 99mTc-labeling of HSA. When HSA was labeled with a stoichiometric concentration of 99Tc, the HMA peak was significantly decreased and new peaks were revealed by absorbance at 280 nm. From these results, the role of HMA in labeling HSA with 99mTc was elucidated. PMID- 1611682 TI - Measurement of conjugated 1 beta-hydroxycholic acid in urine of newborns by specific radioimmunoassay. AB - Anti-tauro 1 beta-hydroxycholic acid antisera were prepared by immunizing rabbits with N-(1 beta,3 alpha,7 alpha,12 alpha-tetrahydroxy-5 beta-cholan-24-oyl)glycine bovine serum albumin conjugate. The immunoglobulin G fraction was obtained by ammonium sulfate precipitation, followed by diethylaminoethyl cellulose column chromatography. The antibody was characterized using [2-3H]tauro 1 beta hydroxycholic acid which has a high affinity (Ka = 1.09 x 10(9) M-1) and reasonable specificity. Cross-reactivity for glyco 1 beta-hydroxycholic acid was 100% and those for other 1 beta-hydroxylated bile acids ranged from 4.32 to 29.6%. Concentrations of conjugated 1 beta-hydroxycholic acid in urine of newborns at 0-20 d after birth were determined by radioimmunoassay to be significant (0.2-11.1 micrograms/ml), exhibiting a tendency to increase during the 20 d after birth. PMID- 1611683 TI - Identification of the carboxymethyllysine residue in the advanced stage of glycated human serum albumin. AB - As an advanced stage of glycation, glycated human serum albumin (G-HSA; glucose content, 2 mol of 5-hydroxymethylfurfural equivalent/mol of HSA) was incubated at 37 degrees C up to 30 d in 0.2 M phosphate buffer, pH 7.4, with 100 microM Fe3+. G-HSA incubated for 30 d (G-HSA-30(Fe)) was subsequently hydrolyzed at 110 degrees C for 24 h in 6 N HCl. In the hydrolysate, N epsilon-carboxymethyllysine (CML) was identified by cochromatography with synthesized CML on an amino acid analyzer. pI of HSA (4.8) shifted to 4.5 in G-HSA. A more acidic fraction, pI 4.3, appeared in G-HSA-30(Fe). CML content (mol of CML/mol of HSA) of HSA and G HSA was as follows; 0 in HSA, 0.2 in HSA-30(Fe), 0.4 in G-HSA and 1.5 in G-HSA 30(Fe) pI 4.3. The amino acid compositions also changed in lysine, arginine and tyrosine at the advanced stage of the reaction. PMID- 1611684 TI - Mechanism of antioxidant action of pueraria glycoside (PG)-1 (an isoflavonoid) and mangiferin (a xanthonoid). AB - The antioxidant activities of pueraria glycoside (PG)-1 (isoflavonoid) and mangiferin (xanthonoid) were studied and compared with PG-3 and daidzein (isoflavonoids) and with wogonin (flavonoid). PG-1 and mangiferin rapidly scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and inhibited lipid peroxidation which was initiated enzymatically by reduced nicotinamide adenine dinucleotide phosphate (NADPH) or non-enzymatically by ascorbic acid or Fenton's reagent (H2O2 + Fe2+) in rat liver microsomes. Wogonin inhibited the enzymatically induced lipid peroxidation but had no scavenging effect on DPPH radical or on the non-enzymatic peroxidation. PG-3 and daidzein did not show any of these effects. Formation of Fe2+ by NADPH-dependent cytochrome P-450 reductase was inhibited by wogonin, but not by PG-1 or mangiferin. PG-1 and mangiferin had no effect on terminating radical chain reaction during the lipid peroxidation in the enzymatic system of microsomes or in the linoleic acid hydroperoxide-induced peroxidation system. These results suggest that PG-1 and mangiferin have an antioxidant activity, probably due to their ability to scavenge free radicals involved in initiation of lipid peroxidation. In contrast, wogonin may affect NADPH-dependent cytochrome P-450 reductase action, since it inhibited only the enzymatically induced lipid peroxidation. PMID- 1611685 TI - Synthesis of (S)-N-[methyl-11C]nicotine and its regional distribution in the mouse brain: a potential tracer for visualization of brain nicotinic receptors by positron emission tomography. AB - A nicotine agonist, 11C-labeled (S)-nicotine, was synthesized by N-methylation of (S)-nornicotine with [11C]-methyl iodide in dimethylformamide-dimethylsulfoxide in order to study nicotinic receptors in the human brain by positron emission tomography. The radiochemical yield of this N-methylation reaction was more than 90% within 5 min. After purification by high performance liquid chromatography the radiochemical purity of the product was more than 99% and the specific radioactivity was 7.4-11.1 GBq/mumol. The regional distribution of (S) [11C]nicotine in the mouse brain after intravenous injection was compared with that of (R)-[11C]nicotine. After injection of (S)-[11C]nicotine, the regional uptake of radioactivity was in the following order: cortex greater than thalamu approximately hippocampus greater than striatum greater than hypothalamus greater than cerebellum. Moreover, (S)-[11C]nicotine was displaced from the brain by unlabeled (S)-nicotine, but unlabeled (R)-nicotine caused no change in uptake. In contrast, (R)-[11C]nicotine showed a lower brain uptake and lesser regional differences in radioactivity. PMID- 1611686 TI - Contribution of interstitial diffusion in drug absorption from perfused rabbit muscle: effect of hyaluronidase on absorption. AB - [3H]Water and [14C]inulin were injected into perfused rabbit muscle with or without hyaluronidase (300 units/ml) and their absorption into venous effluent from muscle was determined. Hyaluronidase accelerated the absorption of both compounds but the enhancement of [14C]inulin was much larger than that for [3H]water. The pharmacokinetic analysis of venous appearance curves based on a physiological diffusion model elucidated that interstitial diffusion of [14C]inulin was remarkably increased by hyaluronidase treatment, suggesting the existence of steric hindrance for it by the polysaccharide network under normal conditions. Enhancement of [3H]water diffusion was also detected although enhancement ratio was about one-half of that of [14C]inulin. Mean time necessary for each process was calculated using the statistical moment concepts. The results suggested predominant contribution of the interstitial diffusion process and secondary and little contribution of local perfusion flow and permeation process across the capillary wall, respectively, in total absorption of [14C]inulin. Effect of hyaluronidase on transcapillary movement of [14C]inulin was studied using an in vitro diffusion experiment with cultured endothelial cell monolayer and no enhancing effect was shown on [14C]inulin transport across the cell monolayer. The contribution of the local perfusion flow, on the other hand, was shown to be almost equivalent to that of the diffusion process in the total absorption of [3H]water. PMID- 1611687 TI - Formulation optimization of sustained-release tablet of chlorpheniramine maleate by means of extreme vertices design and simultaneous optimization technique. PMID- 1611688 TI - Improvement of stability and dissolution of prostaglandin E1 by maltosyl-beta cyclodextrin in lyophilized formulation. PMID- 1611689 TI - Psychotropic effects of Japanese valerian root extract. AB - The psychotropic effects of "Hokkai-Kisso", i.e. roots of Japanese valerian, were compared with those of diazepam and imipramine. Both 30% EtOH extract of valerian root (11.2 g/kg) and diazepam (3 mg/kg) significantly prolonged hexobarbital induced sleep in mice. Spontaneous ambulation and rearing during an open field test were significantly decreased by valerian extract (11.2 g/kg), but kessyl glycol diacetate (KGD, 400 mg/kg) and diazepam (3 mg/kg) significantly increased ambulation. Diazepam (10 mg/kg) significantly decreased approach-avoidance conflict in mice in a water-lick conflict test, but valerian extract and KGD did not. By contrast, valerian extract (4.1 g/kg) and imipramine (20 mg/kg) significantly inhibited immobility induced by a forced swimming test in rats, but did not increase spontaneous motor activity during an open field test just before the forced swimming test. In addition, valerian extract and imipramine significantly reversed reserpine-induced hypothermia in mice. These results indicate that valerian extract acts on the central nervous system and may be an antidepressant. PMID- 1611690 TI - Hapten synthesis for (+)-6-(2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl 2,3,4,5-tet rahydro-8H-pyrido[4',3':4,5]thieno[3,2-f] triazolo[4,3 a][1,4]diazepine (E6123). AB - (+)-6-(2-Chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4, 5-tetrahydro 8H-pyrido[4',3':4,5]thieno[3,2-f]triazolo[4,3-a] [1,4]diazepine (E6123) is a very potent platelet-activating factor (PAF) receptor antagonist and shows potent anti PAF activities at the microgram level in a variety of animal models. In order to examine the pharmacokinetics of E6123 at low doses, establishment of a radioimmunoassay is required. On the basis of the metabolic pattern of E6123, we synthesized 6-[2-chloro-4-(3-carboxypropyl) phenyl]-3-cyclopropanecarbonyl-8,11 dimethyl-2,3,4,5-tetrahydro-8H -pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3 a][1,4]diazepine 22 as a potential hapten. In the synthesis of 22, we developed butynyl carbamate as a piperidine ring N-protecting group to prevent possible side reaction, namely oxidation of the methylene at position 2. This protecting group is stable under usual basic and acidic conditions. PMID- 1611691 TI - Agelasine G, a new antileukemic alkaloid from the Okinawan marine sponge Agelas sp. AB - A new antileukemic alkaloid, agelasine G (1a), has been isolated from the Okinawan marine sponge Agelas sp. and its structure elucidated to be a bromopyrrole alkaloid containing 9-methyladenine and diterpene moieties on the basis of the spectroscopic data. PMID- 1611692 TI - 5-Isoquinolinesulfonamide derivatives. III. Synthesis and vasodilatory activity of 1-(5-isoquinoline-sulfonyl)piperazine derivatives. AB - On the basis of a hypothesis that cyclization and alkylation of the diamine part in formula 1 may give highly active compounds, a new series of 5 isoquinolinesulfonamide derivatives, shown as formula 2, were prepared from cyclic diamines. Their vasodilatory effects were subsequently evaluated in vivo according to the increase in arterial blood flow after the formulas were injected locally to the femoral and/or vertebral arteries of dogs. Cyclization of the diamine structure in formula 1 gave very potent vasodilators: 6 and 14. Acylation and sulfonylation of terminal amino nitrogen afforded much less potent compounds. In contrast to the hypothesis, alkylation on the ring carbon and the terminal nitrogen of the cyclic amine afforded less active compounds except for compound 11. The most active compounds, 6, 11 and 14, showed more potent vasodilatory effects and more selective activity to the vertebral artery than either trapidil or diltiazem. PMID- 1611693 TI - Structure-activity studies of 3-benzoylpropionic acid derivatives suppressing adjuvant arthritis. AB - 3-Benzoylpropionic acid derivatives possess an immunomodulative activity and suppress adjuvant arthritis. To understand how substituents affect the biological activity, the quantitative structure-activity relationships of 30 compounds were analyzed by the adaptive least-squares method. For the suppressing activity in rats, the electronic effects and the structural feature of the substituent on benzene ring were suggested to be important. To reinforce and confirm the correlation, 4 additional compounds of phenoxybutyric acid derivatives were synthesized and tested with the rat adjuvant-induced arthritis. These compounds were found to have potent suppressing activity. PMID- 1611694 TI - Enzyme immunoassay of angiotensin II in human plasma. AB - We established a highly sensitive double-antibody enzyme immunoassay (EIA) for angiotensin (ANG) II. For competitive reactions, the ANG II-antibody was incubated with ANG II standard (or sample) and beta-D-galactosidase-labeled ANG III (delayed addition). Free and antibody-bound labeled antigen were separated using an anti-rabbit immunoglobulin G (IgG) coated immunoplate. The enzyme activity on the plate was fluorometrically determined. The present immunoassay allows detection of 0.4 to 72 fmol/well of ANG II. Using the present EIA, ANG II like immunoreactivity (-LI) in human plasma was determined. The level of ANG II LI in human plasma from 10 healthy volunteers was 33.3 +/- 10.4 pmol/l. PMID- 1611695 TI - Effects of aminotriazole treatment on biosyntheses of primary bile acids in vivo. AB - The influence of aminotriazole treatment on primary bile acid biosynthesis was studied in detail. After administration of aminotriazole to rats, bile was collected for 8 h. The content of chenodeoxycholic acid in the bile was increased to 144% of the control by aminotriazole treatment, but that of cholic acid was decreased to 48.4%. In another experiment, [4-14C]cholesterol was injected into rats immediately after aminotriazole treatment, and then bile was collected. The content of radioactive chenodeoxycholic acid in the bile was significantly increased to 130% of the control, but that of radioactive cholic acid was unchanged. In a similar experiment with [2-14C]mevalonate, the content of radioactive chenodeoxycholic acid in the bile was hardly changed by aminotriazole treatment, but that of radioactive cholic acid was greatly decreased to 41.2% of the control. Aminotriazole treatment did not affect the ratios of tauroconjugate to glycoconjugate of the two bile acids. Thus, aminotriazole treatment affects the syntheses of not only cholesterol (F. Hashimoto, C. Sugimoto and H. Hayashi, Chem. Pharm. Bull., 38, 2532 (1990); F. Hashimoto and H. Hayashi, Biochim. Biophys. Acta, 1086, 115 (1991)) but also primary bile acids in vivo. Namely, aminotriazole treatment activated biosynthesis of chenodeoxycholic acid from exogenous cholesterol, but did not affect that of cholic acid. Aminotriazole hardly affected the synthesis of chenodeoxycholic acid through endogenous cholesterol (from mevalonate), but inhibited that of cholic acid. PMID- 1611697 TI - Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I. AB - Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site. PMID- 1611696 TI - New substances against human immunodeficiency virus: sulfated 5'-nucleotidase inhibitory polyphenols. AB - Two sulfated polyphenols, NF-86II-S-13.3 and NF-86II-S-6.2, were synthesized from NF-86II without sulfur their inhibitory effect on human immunodeficiency virus (HIV) infection in vitro was examined, using cytopathic effect and an antigen expression assay system in MT-4 cells. NF-86II-S-13.3 (sulfur content, 13.3%) completely inhibited the cytopathic effect of HIV and the HIV-specific antigen expression in MT-4 cells at concentrations of more than 6.3 micrograms/ml. The effect of NF-86II-S-6.2 (sulfur content, 6.2%) was much weaker than that of NF 86IIS-13.3. On the other hand, NF-86II without sulfur did not show any activity at all. PMID- 1611698 TI - An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide in rabbit intestine. AB - An assessment of salicylic acid-induced mucosal damage in vivo by measuring the metabolism of salicylamide (SAM) was investigated in rabbit intestine. The intestinal first-pass metabolism of SAM was studied using in situ intestinal sacs with complete mesenteric venous blood collection. The appearance of both SAM and its metabolites into the mesenteric venous blood was measured directly by cannulating the mesenteric vein of exposed intestine and collecting all venous blood draining from the absorbing region. Following oral pretreatment with salicylic acid, the appearance of SAM glucuronide (SAMG) in the mesenteric venous blood was significantly increased compared with the control. The increased blood concentration of SAMG following intraduodenal administration of SAM in vivo was observed in rabbits pretreated with salicylic acid orally. The blood concentration of SAMG after the intravenous administration of SAM was not increased compared with the control. We suggest that the change in the intestinal first-pass metabolism of SAM may be due to the intestinal mucosal damage induced by oral pretreatment with salicylic acid. The measurement of SAM metabolites may be of value in the assessment of intestinal mucosal damage in vivo. PMID- 1611699 TI - An arrhythmic-inducing glycoside from Albizzia julibrissin Durazz, IV. AB - Three pyridoxine derivatives have been isolated from the fresh stem bark of Albizzia julibrissin DURAZZ.. One of them, named julibrin II, was found to exhibit arrhythmic-inducing action. However, neither the others having the same aglycone nor some glycosides having the same sugar unit showed the action. PMID- 1611700 TI - Biochemical appraisal of models for hepatic ischemia-reperfusion injury. AB - Since total hepatic ischemia occurs with transplantation, there has been interest in developing a model which could be used to evaluate interventions to mitigate hepatic ischemic injury. The initial model employed global ischemia of the entire liver which necessitated the placement of a portal-femoral shunt (model A). In 1982, a model of hepatic ischemia was proposed in which ischemia was produced only in the left and median lobes which obviated the need for the shunt (model B). Recently, it has been found that with this model, increased flow to the nonischemic right lobe persists after left reperfusion thus effectively "stealing" blood from the reperfusing left lobe. Occlusion (model C) or removal (model D) of the right lobe on reperfusion have been proposed as techniques to reduce the "steal". We found, that after 30 min of ischemia, the ATP recovery for model B was significantly slower than for either model C or D. Similarly, the AMP content of model B lobes was significantly higher after 15 min of reperfusion, while 30 min after reperfusion, the total adenine nucleotide content was significantly lower in model B compared with models C and D. The energy charge returned to normal within 15 min of reperfusion in model C lobes while it was delayed until 60 min of reperfusion for models B and D. This study provides support for the advantages of right lobe occlusion (model C) over model B for acute studies evaluating the effect of interventions on ischemic injury to the liver and of removal (model D) for survival studies. PMID- 1611701 TI - Cardiovascular mechanisms of thyrotropin-releasing hormone against experimental hemorrhagic shock. AB - Thyrotropin-releasing hormone (TRH) improved mean arterial pressure (MAP) and myocardial contractility (dp/dtmax, -dp/dtmax, Vpm, and Vmax) and increased plasma epinephrine levels significantly at 10 min after TRH treatment in rabbits following shock, but the effects of TRH on MAP and myocardial contractility disappeared in reserpinized rabbits (4 mg/kg, 24 hr pre-treatment, iv). TRH had no effect on myocardial contractility and MAP at 20 and 30 min post-treatment in rabbits pre-treated with the beta adrenergic blocker propranolol (1 mg/kg, 1 hr before TRH treatment, iv), but the alpha adrenergic blocker phenoxybenzamine did not affect these responses to TRH. Experiments in vitro show that although TRH (10(-3) to 10(-8) M) had no direct effects on the isolated heart, left atrium, and aortic strip, it did potentiate the inotropic effects of isoprenaline and dopamine on the left atrium. These results suggest that the antishock effects of TRH are related to adrenergic systems, perhaps acting on the sympathomedullary system to secrete epinephrine and sensitize the beta receptors, but not alpha receptors. Thus, TRH improves cardiac contractility, cardiac output, and hemodynamics during hemorrhagic shock. The sensitization of the beta adrenergic and dopamine receptors may play an important role in the direct peripheral cardiovascular mechanism of TRH effects. PMID- 1611702 TI - Modification of septic shock in mice by the antiglucocorticoid RU 38486. AB - The survival rate in murine septic peritonitis was inversely proportional to the size of the needle used for cecal puncture following ligation below the ileocecal valve. The smaller, 20-gauge needle permitted 20% survival. Only 20% of the animals survived 24 hr after cecal puncture with a 20-gauge needle compared to 90% survival after 5 days if mice had been rendered tolerant to lipopolysaccharide (LPS) prior to the induction of peritonitis. A single intravenous injection of 1 mg RU 38486, concurrent with puncture with a 21-gauge needle, lowered survival to only 15% from the control level of 71%. This same dose of the antiglucocorticoid decreased the survival rate to only 35% from 90% in the tolerant group. Tolerance to the lethal effects of endotoxins, possibly responsible for resistance to septic peritonitis, was also abolished by the antiglucocorticoid. Just 1 mg RU 38486 lowered the survival rate to 5% if it was given with 600 micrograms LPS, which permitted 95% survival in LPS-tolerant mice and 60% survival in normal controls. Whereas both 1 mg RU 38486 and 100 micrograms dexamethasone, given alone, sensitized mice to septic peritonitis (15% and 30% survival, respectively), their combined effects neutralized each other, leading to 80% survival vs. 71% in the control group. Thus receptor-mediated glucocorticoid-dependent mechanisms appear important in the pathogenesis of both endotoxin and septic shock, albeit to varying degrees and in a seemingly contradictory manner. PMID- 1611703 TI - Spontaneous neutrophil activation and the outcome of hemorrhagic shock in rabbits. AB - Recent evidence suggests that an increase in the number of activated circulating polymorphonuclear neutrophils (PMNs), as measured by nitroblue tetrazolium reduction (NBT-positive PMNs), was closely associated with irreversibility in a rat modified Wiggers hemorrhagic shock model. The objective of this study was to utilize a similar model, but in a species with a different hematological profile, the rabbit, to investigate the correlation between the appearance of activated circulating PMNs and survival rate. Rabbits (n = 21) were maintained at 40 mm Hg arterial pressure for 3 hr and observed for 24 hr for survival. This protocol resulted in 33% mortality. There were no significant differences in the number of circulating PMNs before bleeding and during the hypotensive period for survivors and nonsurvivors. During the hypotensive period, fewer circulating NBT-positive PMNs were detected in survivors than in nonsurvivors (P less than 0.01). Since PMN activation was low in most of the rabbits before bleeding, the fatal outcome in this shock protocol was associated consistently with spontaneous PMN activation during the hypotensive period. PMID- 1611704 TI - Polymicrobial sepsis selectively activates peritoneal but not alveolar macrophages to release inflammatory mediators (interleukins-1 and -6 and tumor necrosis factor). AB - While a number of clinical studies indicate that elevated serum cytokine [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor (TNF)] levels are associated with enhanced mortality in sepsis, the time course and the role that different macrophage (M phi) populations play in releasing these cytokines remain to be determined. To study this, polymicrobial sepsis was induced in C3H/HeN mice by cecal ligation and puncture (CLP). The animals were then sacrificed at 1, 4, or 24 hr post-CLP. Blood was taken for serum cytokine level determination. Macrophages, of either peritoneal (PM phi) or alveolar (AM phi) origin, were harvested by lavage, and their innate vs. inducible cytokine productive capacities were assessed by incubation with or without endotoxin (lipopolysaccharide; LPS). Serum levels of TNF were significantly enhanced 1 hr post-CLP (CLP = 3.8 +/- 2.4* vs. sham = 0.4 +/- 0.9 U/ml; P less than 0.05 by t test). However, not until 4 hr post-CLP were marked increases in IL-6 observed (CLP = 318.0 +/- 209.0* vs. sham = 1.1 +/- 0.5 U/ml), which remained elevated through 24 hr post-CLP (CLP = 11.3 +/- 15.0* vs. sham = 0.03 +/- 0.02 U/ml). Cytokine release (IL-1, IL-6, TNF) from PM phi (without the addition of LPS) was detectable only in cells harvested 1 h following CLP. Alveolar M phi from septic mice showed little in vivo activation. Septic PM phi IL-1 and IL-6 production was markedly depressed at all time points with LPS stimulation, but TNF release remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611706 TI - Endotoxin alteration of muscle microvascular renin-angiotensin responses. AB - Endotoxin decreases arteriolar sensitivity to norepinephrine and sympathetic neural activity, but vasopressin sensitivity is increased. Vascular responses to the renin-angiotensin system may also be altered by endotoxin (ENDT). Reactivity of cremaster muscle microvessels of pentobarbital anesthetized Wistar rats was studied using videomicroscopy. Escherichia coli endotoxin (6 mg/kg) was infused i.v. over a 1 hr period. Femoral arterial pressure (Pm) and arteriolar diameter changes, to i.a. bolus injections (60 ng) of angiotensin II (AII) were obtained in Group A at control and at 30 and 90 min post-ENDT, and in Group B at control, 30 min after continuous infusion of saralasin (10 micrograms/min/kg) began, and at 30 and 90 min post-endotoxin. In Group A, the control Pm was 106 +/- 4 mm Hg, and at 30 and 90 min post-ENDT was 96 +/- 4 and 89 +/- 7 mm Hg. All increased Pm 29 +/- 4% before ENDT but the increase was significantly less (P less than .05) at 7 +/- 1% and 6 +/- 1% 30 and 90 min post-ENDT. In Group B, the control Pm was 116 +/- 6 mm Hg, 103 +/- 5 after saralasin, 85 +/- 2 after ENDT infusion, and 83 +/- 4 and 63 +/- 8 mm Hg at 30 and 90 min post-ENDT. All increased Pm 34 +/- 7% before saralasin but only 5 +/- 2% (P less than .05) during saralasin infusion. In Group A, the A1 and A2 arterioles were constricted significantly more post endotoxin by AII than during control. A3 arterioles post-endotoxin were constricted similar to control amounts by AII.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611705 TI - Effect of amrinone on tumor necrosis factor production in endotoxic shock. AB - Tumor necrosis factor (TNF) is a macrophage-derived mediator responsible for many of the pathophysiologic manifestations of endotoxic shock. We now demonstrate that amrinone, a noncatechol inotrope, strongly inhibits lipopolysaccharide (LPS) induced TNF production at concentrations readily achieved in vivo. This inhibition is apparent in murine macrophages, in macrophage cell lines, in vivo, and in cell lines containing a reporter gene construct that substitutes the chloramphenicol acetyl transferase (CAT) coding sequence for the TNF coding sequence and introns. Inhibition by amrinone (like inhibition by pentoxifylline) is manifested at the level of mRNA accumulation, in contrast to inhibition caused by dexamethasone. Combined application of dexamethasone and amrinone caused additive inhibition of TNF biosynthesis in vitro. Furthermore, treatment of mice with amrinone immediately prior to endotoxin challenge led to significantly improved survival. These findings suggest that amrinone possesses antiinflammatory as well as inotropic properties that may make it an appropriate agent for use in septic shock or other serious bacterial infections. Abrupt removal of amrinone or pentoxifylline from the culture medium prior to LPS stimulation, however, caused significantly augmented TNF production. Therefore, amrinone and other phosphodiesterase inhibitors may also enhance sensitivity to LPS during a period of time following discontinuation of therapy. PMID- 1611707 TI - Hypertonic NaCl solution prevents bupivacaine-induced cardiovascular toxicity. AB - The effects of various hypertonic solutions on the intraventricular conduction disturbances and on the cardiac arrhythmias caused by the intravenous (i.v.) injection of bupivacaine were studied in sodium pentobarbital anesthetized mongrel dogs. Bupivacaine was injected in 2 doses: 3.0 mg/kg and 6.5 mg/kg. Hypertonic solutions, given intravenously 5 minutes before bupivacaine, were 7.5% NaCl, 5.4% LiCl or 50% glucose (2,400 mOsm/l, 5 ml/kg), or 20% mannitol (1,200 mOsm/l, 10 ml/kg). The highest dose of bupivacaine induced severe cardiac arrhythmias and intraventricular conduction disturbances, as reflected by significant increases in QRS complex duration, HV interval and IV interval, as well as a severe hemodynamic impairment. Significant prevention against intraventricular conduction disturbances and ventricular arrhythmias was observed with 7.5% NaCl (QRS complex duration percent increase: 164 +/- 21% in the non pretreated group vs. 75 +/- 14% in the pretreated group, P less than .01; HV interval percent increase: 131 +/- 16% in the non pretreated group vs. 58 +/- 7% in the pretreated group, P less than .01; cardiac index percent decrease: 46 +/- 6% in the non pretreated group vs. 28 +/- 5% in the pretreated group, P less than .025). The three other hypertonic solutions were ineffective. These findings suggest an involvement of sodium ions in the mechanism of hypertonic protection. PMID- 1611708 TI - Hemorrhagic hypotension impairs endothelium-dependent relaxations in the renal artery of the cat. AB - The effect of hemorrhagic shock on the vasodilatory responses of the feline renal artery was studied in vitro. In sodium pentobarbital anaesthetized cats, a steady level of hypotension (50 mm Hg) was reached by bleeding into a reservoir and maintained at this level by further bleeding or autotransfusion for 2 hr (shock). One to 3 mm long rings of the arteries (from control and shocked animals) were suspended for isometric tension recording in organ chambers filled with modified Krebs-Henseleit solution, aerated with 95% O2-5% CO2 at 37 degrees C. The experiments were performed in the presence of indomethacin and propranolol to inhibit cyclooxygenase activity and beta-adrenoceptors, respectively. Endothelium dependent relaxations induced by acetylcholine and ATP were significantly inhibited in the vessels after hemorrhagic shock. In contrast, endothelium independent vasodilation induced by adenosine remained unchanged after this shock state. The present results suggest a marked and selective impairment of the endothelial function of the renal artery of hemorrhagic shock. This alteration of the renovascular reactivity might play an important role in the development of vasoconstriction in the renal vasculature during and after this hemorrhagic shock state. PMID- 1611709 TI - Studies of luminal and mucosal pH in reflux esophagitis and antral gastritis. AB - Luminal and mucosal pH were measured endoscopically in patients with reflux esophagitis and antral gastritis and in control subjects. In all subjects, significant lumen-to-mucosa gradients were observed in the esophagus, stomach and acidified proximal duodenum. In the reflux patients luminal pH was lower in the fundus (mean +/- SEM, control vs. reflux esophagitis: 2.01 +/- 0.17 vs. 1.32 +/- 0.18; p less than 0.02) and antrum (3.51 +/- 0.35 vs. 2.13 +/- 0.24; p less than 0.01) and, in the gastritis patients, in the fundus (2.01 +/- 0.17 vs. 1.3 +/- 0.17; p less than 0.02). In both patient groups, mucosal pH was lower in the fundus (control vs. reflux vs. gastritis: 4.84 +/- 0.37 vs. 3.37 +/- 0.61 vs. 3.12 +/- 0.6; p less than 0.05) and acidified duodenal cap (6.74 +/- 0.13 vs. 6.09 +/- 0.24 vs. 5.73 +/- 0.46; p less than 0.03). Mucosal pH profiles at the various sites showed less resistance of the gradient to a highly acidic environment in both the lower esophagus and antrum than in fundus and duodenum, and this was the case in the patient and control groups. Though associated with a more acid environment, neither esophagitis nor antral gastritis exhibits a specific deficit in the 'mucus-bicarbonate barrier', suggesting that the pathogenesis of these disorders may depend more on abnormal 'attack' rather than impaired defense. PMID- 1611710 TI - 'Gastrospirillum hominis', another gastric spiral bacterium. AB - 'Gastrospirillum hominis' is a 'new' tightly coiled gram-negative bacterium carrying bundles of sheathed polar flagella. It has been rather infrequently detected in antral and, even more rarely, in fundic mucosa samples removed at endoscopy from patients investigated for Helicobacter pylori colonization. Until now, it has remained noncultivable but has successfully been maintained in laboratory mice. Its identity with similar bacteria found in the stomachs of cats, dogs, monkeys, pigs, and other animals is uncertain. It was probably already seen by early investigators in the first half of this century. Preliminary data published in case reports suggest that it is associated with more or less active chronic antral gastritis, that it is restricted to the gastric epithelium, and that it possesses a urease, thus limiting the specificity of urease tests for H. pylori. There is hitherto no solid proof that it can induce inflammation although it seems capable of invading parietal and other glandular cells and causing ultrastructural changes. Similar organisms spontaneously colonizing the stomachs of rhesus monkeys were shown to increase gastric acid secretion. PMID- 1611711 TI - Role of sucralfate in peptic disease. AB - Sucralfate, a basic aluminum salt of sucrose, was the first successful drug with a major cytoprotective mechanism of action. It binds bile acids and pepsin and adheres to both ulcerated and nonulcerated mucosa. Sucralfate stimulates the synthesis and release of gastric mucosal prostaglandins as well as bicarbonate and the epidermal growth factor which stimulates healing. Sucralfate is the safest drug available today in the treatment of dyspeptic symptoms and compared to ranitidine and cimetidine it has the following characteristics. (2) The short term healing of duodenal ulcers is the same for sucralfate, cimetidine and ranitidine. (3) Sucralfate-treated patients have a lower recurrence rate of duodenal ulceration after healing when compared with cimetidine and the recurrence rate is not connected with the presence or absence of Campylobacter pylori. PMID- 1611712 TI - Clotting abnormalities in chronic liver disease. AB - In patients with chronic liver disease (CLD), several clotting changes can be observed. The most frequent abnormality is the reduced synthesis of many clotting factors, including vitamin-K-dependent and vitamin-K-independent ones. A low platelet count is another frequent feature of patients with CLD, which, however, is not always associated with the prolongation of bleeding time. Hyperfibrinolytic syndrome is usually seen in patients with decompensated state, and may further deteriorate the clotting abnormalities and favor bleeding complications. The assessment of the clotting system may be a useful approach to evaluate liver function and predict prognosis of patients with CLD. PMID- 1611713 TI - Hepatobiliary and gastrointestinal manifestations of acromegaly. AB - Acromegaly is a unique condition characterized by chronic growth hormone (GH) and insulin-like growth factor-1 (IGF-1) hypersecretion usually due to a pituitary adenoma. Rarely, acromegaly can result from a GH-releasing hormone carcinoid or pancreatic neoplasm which stimulates the normal pituitary to secrete GH. This review describes the interactions between acromegaly and the gastrointestinal system. In contrast to the soft tissue and skeletal changes, clinical organomegaly of the liver, kidney, and spleen is unusual in patients with acromegaly and should warrant further investigations. The prevalence of cholelithiasis is notably increased by the use of the otherwise effective GH lowering somatostatin analog, octreotide. Patients on long-term therapy with this agent may require anticholelithogenic treatment. The frequency of malignant and premalignant polyps of the colon justify the routine screening for these lesions in newly diagnosed patients with acromegaly. PMID- 1611714 TI - Autoantibodies to major and minor nuclear lamins are not restricted to autoimmune diseases. AB - Autoantibodies to lamins, the major polypeptide components of the nuclear lamina, have been reported in selected sera from patients with autoimmune diseases, including anti-lamin B in systemic lupus erythematosus (SLE) and anti-lamins AC in autoimmune chronic active hepatitis (CAH). We have studied the frequency, specificity, and isotypy of autoantibodies to major and minor lamins by immunoblotting on purified rat liver lamins in 190 sera from normal controls (n = 62), rheumatic disease controls (n = 42), and autoimmune disease patients (n = 86). The frequency of anti-lamin in normal controls was 85.5%, and ranged from 77 to 100% in the other groups. Anti-lamin frequency was not related to age, sex, or disease duration. Reactivity with lamin A or with minor lamins only was observed with 7 various sera and 2 normal sera, respectively. Between groups, the proportions of reactive sera were not different for lamins AC (18-47%) and for lamin B (22-36%). In particular, anti-lamin B and anti-lamins AC were not more common in SLE or CAH than in normal sera. The most frequent lamin specificity of SLE sera was anti-lamins ABC. Anti-lamin isotypes were IgG and/or IgM. Titers of IgM antibodies were not higher in any group. However, IgG anti-lamin titers were higher in CAH than in normal, ankylosing spondylitis, or SLE sera. The highest end point titers (greater than or equal to 1:3200) were observed with CAH, SLE, and rheumatoid arthritis (RA) sera with IgG anti-lamins AC, B, or ABC, or with IgM anti-lamins ABC. None of these SLE and RA patients had evidence of liver disease. Reactivity with minor lamins was more frequent in CAH. We conclude that anti-lamin autoantibodies are present in sera from most individuals and that the highest titers are found in sera from patients with autoimmune diseases. PMID- 1611715 TI - Increases in soluble CD8 antigen in plasma, and CD8+ and CD8+CD38+ cells in human immunodeficiency virus type-1 infection. AB - Increases in plasma levels of soluble CD8 (SCD8) antigen and expansion of the CD8+ CD38+ lymphocyte compartment were early immunologic alterations frequently observed prior to detection of antibodies against human immunodeficiency virus type 1 (HIV-1) and diminution of CD4+ cells in subjects at risk to develop AIDS. These increases identified in the 49 seronegative homosexual men were manifest in all 164 homosexual subjects and 45 intravenous drug users (IVDU) positive for HIV 1 antibodies (HIV-1+), 19 patients with ARC, and 29 AIDS patients. Augmentation of plasma sCD8 antigen correlated with increases in both CD8+ and CD8+ CD38+ cells in HIV-1(-) homosexual men (r = 0.35, P less than 0.013; r = 0.48, P less than 0.0005; respectively) and the 258 HIV-1+ subjects (r = 0.25, P less than 0.0003; r = 0.33, P less than 0.0001, respectively). In vitro examination of unstimulated peripheral blood lymphocytes from HIV-1+ homosexuals and IVDU confirmed the fivefold higher constitutive levels of cellular release of sCD8 antigen in these subjects compared to heterosexual controls. Inclusion of radiolabeled amino acids during the 3-day culture period in the presence or absence of phytohemagglutinin resulted in negligible levels of radioactivity associated with the sCD8 antigen indicative of a lack of de novo synthesis. Throughout clinical progression to AIDS, sCD8 antigen levels continued to escalate relative to the numbers of CD8+ cells bearing CD38+ antigen. The data confirm the interrelationship between sCD8+ antigen and CD8+ and CD8+ CD38+ cells. PMID- 1611716 TI - T and B cell responses to neutrophil cytoplasmic antigens in systemic vasculitis. AB - The systemic vasculitides (SV) are characterized by the presence of autoantibodies to neutrophil cytoplasmic antigens (ANCA). The role of T cells in SV is uncertain. We studied human and murine T cell responses to human neutrophil cytoplasmic antigens in vitro. T cells from mice immunized with the neutrophil extract showed dose-dependent antigen-specific proliferation, restricted by the MHC class II E molecule. Myeloperoxidase (MPO) was not an important target antigen for murine T cells. Peripheral blood lymphocytes (PBLs) were obtained from 36 patients with SV, 31 before the start of immunosuppressive therapy, and from 11 healthy controls. T cell responses to the neutrophil extract in vitro did not differ between patients and controls: there were only low levels of antigen specific proliferation, and this could not be amplified by in vitro selection. In 3 patients and 2 normals, PBLs were also tested after the depletion of CD8+ cells; this did not unmask T cell reactivity to neutrophil extract. The lack of demonstrable T cell reactivity to this antigen preparation may indicate that T cells do not play an important effector role in these diseases. A solid-phase spot ELISA was adapted to demonstrate autoantibody-producing B cells in vitro. Low numbers of ANCA-producing B cells could be demonstrated in the majority of patients. B cells producing antibody to MPO could be demonstrated in most patients and in three laboratory staff, but not in normals from outside the laboratory. In 2 patients, sequential B cell spot ELISAs were performed during the introduction of therapy, and autoantibody-producing B cells rapidly decreased in number. This assay may therefore be useful in monitoring the effects of treatment at the cellular level. PMID- 1611717 TI - Pathways of coagulation activation in situ in rheumatoid synovial tissue. AB - Immunohistochemical techniques were applied to rheumatoid synovium in order to detect components of coagulation and fibrinolysis pathways within these tissues. These techniques revealed an intact coagulation pathway and plasminogen activator inhibitor-2 associated with macrophage-like cells that were present throughout these tissues, especially in subsurface areas. Cell-associated thrombin generation appeared to account for conversion of abundant fibrinogen to fibrin. Occasional macrophage-like cells also stained for urokinase but tissue-type plasminogen activator and plasminogen activator inhibitor-1 were restricted to vascular endothelium. Intense synovial fibrin deposition (with the limited evidence for associated fibrinolysis) may contribute to local inflammation and explain certain clinical features of rheumatoid arthritis. These findings suggest novel treatment hypotheses for this disease. PMID- 1611718 TI - Impaired generation of polyclonal T cell-mediated cytolytic activity despite normal polyclonal T cell proliferation in systemic lupus erythematosus. AB - No differences in proliferation induced by the anti-CD3 MAb 454 were detected between systemic lupus erythematosus (SLE) and normal peripheral blood mononuclear cells (PBMC) or purified T cells. In contrast, overnight culture with soluble MAb 454, immobilized MAb 454, or rIL2 induced significantly less increase in cytolytic activity against Daudi targets in SLE PBMC than in normal PBMC. Cytolytic activity in SLE PBMC cultures sequentially stimulated with soluble MAb 454 and rIL2 over a 6-day period overall was also lower than normal (with approximately 50% of the individual SLE cultures generating clearly subnormal levels of cytolytic activity) and did not correlate with the daily corticosteroid dose or with the presence of nephritis. Phenotypic analysis of soluble MAb 454 stimulated SLE PBMC cultures maintained for up to 23 days in rIL2 indicated that greater than 90% (and often greater than 96%) of the recovered cells were CD3+. Cytolytic activity generated in cultures of purified T cells stimulated with soluble MAb 454 + rIL2 over a 6-day period was also subnormal in 4/8 SLE donors, suggesting that the impaired generation of cytolytic activity in SLE is caused, at least in part, by impaired T cell-mediated cytolytic activity. Taken together, these observations demonstrate that normal CD3/T cell antigen receptor (TCR) triggered polyclonal T cell proliferation can be dissociated from abnormal CD3/TCR-triggered polyclonal T cell cytolytic activity in SLE. This may have important implications for the pathogenesis of SLE and/or for the immunocompromised state seen in SLE. PMID- 1611719 TI - Renal platelet-derived growth factor gene expression in NZB/W F1 mice with lupus and ddY mice with IgA nephropathy. AB - The present study was carried out to determine how platelet-derived growth factor (PDGF)-A and -B chain mRNA expression correlate with disease activity in the renal cortex of NZB/W F1 mice, a model of systemic lupus erythematosus, and ddY mice, a model of IgA nephropathy. The PDGF-A and -B chain mRNA levels increased significantly as nephritis progressed in NZB/W F1 mice. In the renal cortex of ddY mice, however, the PDGF mRNA levels increased slightly with age. The PDGF mRNA levels in ddY mice were lower than those in NZB/W F1 mice. In the NZW control kidneys, the PDGF mRNA levels changed minimally throughout the experiments. A positive correlation was noted between PDGF mRNA levels and histopathological changes in renal tissues. At the onset of nephritis, NZB/W F1 mice were divided into two groups that received either methylprednisolone (MPSL) or saline injections for 5 months. The development of histopathological lesions and the increased PDGF mRNA levels were suppressed by MPSL treatment. These data suggest that PDGF plays a role in the progression of nephritis and that the beneficial effect of MPSL correlates with its ability to decrease the abnormally high PDGF mRNA levels seen in lupus nephritis. PMID- 1611720 TI - Human recombinant interleukin-4 induces proliferation and interleukin-6 production by cultured human skin fibroblasts. AB - The effect of human recombinant interleukin-4 (hrIL-4) on normal human adult dermal fibroblasts in terms of proliferation and IL-6 production was studied. Fibroblasts were exposed to different concentrations of IL-4 for various periods of time. Proliferation was measured using a [3H]thymidine incorporation assay. IL 6 production was measured at the transcriptional, protein, and functional levels by Northern blot analysis, radioimmunoassay, and B9 bioassay, respectively. Our results show that hrIL-4 significantly stimulated (two- to fivefold) fibroblasts to increase the incorporation of [3H]thymidine in a dose- and time-dependent manner. However, hrIL-1, hrIL-2, hrIL-5, or hrTNF alpha, at the same concentration (100 U/ml) and for the same time period (4 days), did not. In addition, IL-4 significantly induced (four- to eightfold) the production of immunoreactive and biologically functional IL-6. However, IL-4 was not as potent an inducer of IL-6 as IL-1. The IL-4-induced IL-6 production was dose and time dependent and was due, at least in part, to a dramatic increase in the steady state levels of IL-6 mRNA. This is the first report describing the ability of IL 4 to activate human dermal fibroblasts in terms of proliferation and IL-6 production. PMID- 1611721 TI - Enhanced release of cytokines, interleukin-2 receptors, and neopterin after long distance running. AB - This study was designed to examine cytokine production in a group of 22 well trained runners covering a distance of 20 km within 2 hr. After running, all participants displayed a marked granulocytosis for 7 hr. Plasma neopterin levels increased 1 hr after exercise for 24 hr. Except for interleukin-6 (IL-6), cytokines were not reliably detected in plasma but were present in urine. Already before exercise, cytokines were detected in the urine of runners when compared to sedentary controls. Directly after running, interferon-gamma and tumor necrosis factor-alpha were further elevated but rapidly declined to preexercise levels. Interleukin-1 beta and interleukin-6 increased at a slower rate after exercise but secretion into urine persisted longer until 12 and 7 hr, respectively. Interleukin-2 (IL-2) was not detected but soluble IL-2 receptors appeared in the urine directly after running. Enhanced cytokine levels were accompanied by an only low creatinin kinase increase, indicating little muscle damage. These data show that long-distance running elevates cytokine production which supports the concept that regular, but not excessive, physical exercise may be beneficial by maintaining a stimulated immune system. PMID- 1611722 TI - Increased interleukin-2 level in patients with primary hypothyroidism. AB - The effects of hypothyroid status in humans on cytokine blood levels have been studied. Evaluations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), thyrotropin, thyroxine, and triiodothyronine were performed in seven patients with primary hypothyroidism and eight euthyroid healthy control subjects on the basis of venous blood samples collected after an overnight rest. A normal level of IL-1 beta (23 +/- 15 fmol/ml) and an increased IL-2 level (82 +/- 56 fmol/ml) have been shown in hypothyroid patients versus controls (IL-1 beta, 24 +/- 5 fmol/ml; IL-2, 33 +/- 13 fmol/ml). The possible role of thyroid hormones and of an autoimmune mechanism in the link with increased IL-2 blood level in hypothyroidism in man have been discussed. PMID- 1611723 TI - Immunohistological alterations in muscle of patients with amyotrophic lateral sclerosis: mononuclear cell phenotypes and expression of MHC products. AB - Muscle biopsy specimens from 15 autopsied patients with the isolated form of amyotrophic lateral sclerosis were examined by routine histological and immunocytochemical methods using a panel of monoclonal antibodies directed against differentiation and activation markers of immunocompetent cells. In 12 cases, cellular infiltrates consisting mainly of T-cells and macrophages were seen. Both CD8+ and CD3+ cells, in juxtaposition with OKM1+ macrophages, were particularly seen in the atrophied parts of muscle. The majority of the T-cells appeared to be of the CD4+ T-helper/inducer type, whereas the CD8+ T suppressor/cytotoxic cells were only rarely and focally present. On the other hand, B-, NK- and K-cells were infrequently seen. Most of the T-cells and macrophages surrounding the atrophied muscle fibers were in an activated state, as indicated by their intense HLA DR expression. In addition, some angulated degenerated fibers showed strong endomysial positivity for HLA DR in the regions where T-cells and macrophages were present in clusters. The immunoreactive changes in ALS-associated muscle atrophy are very similar to those reported for exercise-induced damage and some forms of myositis. The present study shows that the expression of major histocompatibility complex products and the relative numbers of infiltrating immunocompetent cells are closely associated with the extent of destruction of muscle fibers in ALS. PMID- 1611724 TI - Intravascular papillary endothelial hyperplasia at the fissura orbitalis superior: a case report. AB - We report on a 27-year-old female suffering from headaches and nervus abducens paresis. Operation surprisingly revealed an intracranial intravascular papillary endothelial hyperplasia (IPEH) at the left fissura orbitalis superior visualized angiographically as a widening of the left ophthalmic artery. Clinical symptoms completely disappeared after the operation. IPEH is considered to be a rare benign lesion. Intracranial location has been reported only four times. The present case is the first IPEH described at the fissura orbitalis superior. PMID- 1611725 TI - Epidemiologic data on meningiomas in East Germany 1961-1986: incidence, localization, age and sex distribution. AB - From 1961 to 1986, 8119 new cases of meningioma were reported to the National Cancer Register of East Germany (former German Democratic Republic) with an average population of 16.9 million. The crude annual incidence was 1.85 per 100,000 population. The crude rates were 1.16 for males, and 2.44 per 100,000 for women; after age adjustment ("world" population) these rates were 0.90 and 1.92 per 100,000, respectively. Thus meningioma occurred 2.1 times more frequently in women than men. Independent of sex, the incidence rose continuously with increasing age. At the same time, there appeared to be an increase in meningioma frequency in the course of the 26-year reporting period. The overwhelming majority of cases, 7375, (90.8%) were intracranial in location but 711 (8.8%) were intraspinal. Some 50% of all cases were first discovered at autopsy, with the proportion of such cases being markedly higher in the older age groups. PMID- 1611726 TI - Progressive bulbar dysfunction caused by a predominantly venous vascular malformation of the medulla oblongata. AB - We describe a 58-year-old patient with a rare predominantly venous vascular malformation of the medulla oblongata, which caused a progressive bulbar dysfunction consisting of hiccoughs, dysphagia, hoarseness, dysarthria, gait ataxia and dysuria over a period of 11 months. On autopsy, a large dilated vein with focal marked intimal fibroelastic thickening was present on the ventral surface of the medulla. Microscopically, moderate proliferation of capillaries and veins was observed which was confined primarily to the medulla. The veins displayed abnormal dilatation and tortuosity; prominent thickening of vessel walls was also present in the veins and capillaries. The venous abnormalities were prominent in the parenchyma of the medulla, but much less apparent in its subarachnoid space. Multifocal neuronal loss and gliosis were observed, most prominently in the inferior olives, hypoglossal, dorsal vagal and ambiguus nuclei. The histopathologic findings suggested that abnormal venous drainage within the parenchyma of the medulla was the most critical factor for the pathogenesis of this patient's neurologic symptomatology. PMID- 1611727 TI - Lumbar spinal stenosis and spondylosis associated with amyloid deposition in the ligamentum flavum. AB - Thickening (hypertrophy) of the ligamentum flavium is one of the many anatomical abnormalities associated with lumbar stenosis and spondylosis. In twelve of 97 patients who had decompression laminectomy the thickened ligamentum flavum contained abundant amyloid in both light and electronmicroscopic preparations. Since the cases were collected over a period of two years from the practice of a single neurosurgeon, its appears to be a common finding, and is age related. In all cases CT and MR scans showed a prominent ligamentum flavum. Nevertheless, there was not a well-defined clinicopathological correlation. The pathogenesis is not clear. PMID- 1611729 TI - The Rancho mounting technique for the Ilizarov method. A preliminary report. AB - To improve implant tolerance and muscle function associated with circular external fixation, the authors substituted divergent titanium pins for the tensioned steel wires used to mount the Ilizarov apparatus on a limb. The first ten patients treated with half-pins were compared to the last ten patients managed with tensioned wires. While the conditions were not exactly comparable, the half-pin group showed improvement over the wire group in categories including time in fixation, implant-site sepsis, range of joint motion, pain medication requirements, and ambulatory capacity. Half-pin mountings require special techniques for a successful application. PMID- 1611728 TI - Lobar atrophy without Pick bodies. AB - Four patients from the Kathleen Price Bryan Brain Bank with clinical Pick's syndrome are presented. Thorough neurological evaluation revealed no evidence of a movement disorder. The brains showed marked knife-blade type atrophy of the frontal and temporal lobes with relative sparing of the superior temporal gyrus and parietal and occipital lobes. There was marked caudate atrophy in all four. Histologically there was severe neuronal loss and gemistocytic astrocytosis in the involved areas with marked myelin pallor in the deep white matter and subcortical gliosis. There was sometimes marked spongiform change in cortical layer 2. There was severe neuronal loss and gliosis of the caudate nucleus. The gross and microscopic features were characteristic of Pick's disease except that careful search failed to uncover either Pick's bodies or Pick's cells. Review of the literature revealed that fronto-temporal cortical and caudate atrophy with clinical features of Pick's disease has received many different names including Pick's disease type C, Pick's disease type II, progressive subcortical gliosis, presenile glial dystrophy, long duration Creutzfeldt-Jakob disease, frontal lobe degeneration, dysphasic dementia, and dementia lacking distinctive histologic features. Nevertheless, the morphologic findings in the present cases so closely resemble Pick's disease that they may well represent endstage Pick's disease. In our experience, such cases account for a significant proportion of non-Alzheimer disease dementia. PMID- 1611730 TI - Biomechanics of the Ilizarov external fixator. AB - The Ilizarov external fixator exhibits more isotropic mechanical properties in bending and nonlinear axial stiffness than do unilateral and bilateral external fixators. Each frame element--wire size, tension, and orientation, as well as ring type--contributes to overall frame rigidity and stability. These factors and the specific clinical situation must be considered for the successful application of the Ilizarov fixator. PMID- 1611731 TI - Techniques for the management of burn contractures with the Ilizarov Fixator. AB - The Ilizarov fixator was used to correct chronic burn deformities of the foot and ankle. These contractures can be classified as "simple" or "complex" based on associated deformities and musculoskeletal function. The simple, undirectional deformities of equinus, cavus, rockerbottom, and toe dislocations are fairly easy to correct and maintain. Correction and maintenance of complex deformities with varus or valgus angulation, bone abnormality, or muscle loss are more difficult. PMID- 1611732 TI - Management of unstable open and closed tibial fractures using the Ilizarov method. AB - Forty-one consecutive tibial diaphyseal fractures that required operative stabilization were treated using the external fixator and concepts of compression distraction of Ilizarov. Eleven fractures had bone loss greater than 1 cm and were managed by simultaneously compressing the fracture gap and distracting through a corticotomy site to maintain extremity length. Thirty tibial fractures consisted of closed unstable and open fractures that were managed using the external fixator, emphasizing immediate weight bearing and gradual compression at the fracture site. Twenty-six fractures in 23 patients were available for follow up evaluation six to 9.5 months after bone healing. There were six closed, two Grade I, eight Grade II, five Grade IIIA, and five Grade IIIB fractures. Serial wound debridements, wet-to-dry-dressing changes, wound- and fracture-site compressions (13 fractures), and split-thickness skin grafts (eight wounds) were used to accomplish wound closure. Chronic infections did not occur. All fractures healed from 12 to 47 weeks without bone grafting. Eight transosseous fixation wires are used, only two of which transfixed significant muscle. Approximately 10% of the 248 wire sites became inflamed and nine wire sites were treated for infection with antibiotics, skin release around the offending wire, or wire removal. Three wires fractured and one wire was replaced. One ring sequestrum occurred and responded to curettement. Angulation of 7 degrees-9 degrees occurred in five fractures (19%). The results were good or excellent in 25 fractures. One patient with 9 degrees varus in a distal fracture refused correction. Operative time was 60 to 90 minutes after developing a satisfactory protocol for frame application. This method allows immediate functional stabilization of tibial diaphyseal fractures and postoperatively allows ease of fracture gap closure and compression. The frame can be left in place for the duration of the fracture care. Application of the Ilizarov external fixator is slightly more complicated than traditional large pin fixators and requires more attention to detail intraoperatively and postoperatively, but can be a versatile tool in the management of complex tibial shaft fractures. PMID- 1611733 TI - Management of segmental defects by the Ilizarov intercalary bone transport method. AB - Seventeen patients with segmental skeletal defects were managed with the Ilizarov intercalary bone transport method, whereby an osseous defect is eliminated by elongating one fragment. On average, the regenerate new bone length measured 5.14 cm, corresponding to the creation of new osseous tissue equaling 13.7% of the bone's original length (range, 4.2%-35%). The average time in fixation was 9.6 months, including 4.8 months to transport the bone fragment throughout the limb. Numerous complications were encountered, most commonly wire-site sepsis and fixator instability. No serous nerve or vessel complications occurred. All but one patient eventually healed, although six patients required bone grafts, five at the target site and one at the level of the regenerate. Most of the difficulties encountered were due to a lack of technical knowledge with the method. PMID- 1611734 TI - The treatment of infected nonunions and segmental defects of the tibia by the methods of Ilizarov. AB - Circular external fixation using the Ilizarov apparatus combined with internal bone transport or compression-distraction techniques were used to treat 28 patients with infected nonunions or segmental bone loss of the tibia. There were 22 males and six females with an average age of 34 years (range, 17-58 years). Six of 28 patients had infected tibial nonunions associated with hemicircumferential bone loss. These tibiae were treated by anterior hemicircumferential corticotomy and partial bone fragment internal transport. Fifteen of the remaining 22 patients had an average of 4 cm of segmental bone loss (range, 2-7 cm). Seven patients without shortening or defect had infected nonunions associated with extensive diaphyseal sequestrae. These nonunions were treated by en bloc resection of the diaphyseal shaft and internal bone transport. All patients healed their infected extremities without the addition of cancellous bone graft, microvascular fibular, or soft-tissue grafting. Preoperative shortening was present in 13 of 28 patients. Regenerate new bone formation averaged 6 cm (range, 1.5-22 cm). Postoperative antibiotics were not administered in 21 of 28 patients. In seven patients, antibiotics were given for ten days after en bloc resection of the diaphyseal sequestrae. Equal limb length was maintained in 21 extremities, within 1 cm in five tibiae and less than 3 cm in two tibiae. Functional results were good to excellent in 21, fair in six, and poor in one. The application of Ilizarov techniques to diaphyseal infected nonunions and segmental defects is very encouraging. It may prove to be an excellent technique for future management of resistant diaphyseal infections of bone. PMID- 1611735 TI - Biomechanics of the Ilizarov fixator for fracture fixation. AB - Compression, distraction, and torsion stiffness of the Ilizarov external fixator was measured in two fracture models in autopsy specimens of tibia and fibula. A transverse model was tested in six frame constructions with the osteotomy site preloaded in four different positions. An oblique model was tested in four frame constructions also with four preloaded positions. Stiffness was more dependent on bone preload than wire number, wire type, or frame design. High stiffness was achieved by bone preloading, by compressing the rings together, by increasing the number of wires, and by using olive wires. The stiffness can be decreased (dynamization) by separating the rings and by removing wires. This data is helpful for frame design of the Ilizarov fixator. PMID- 1611736 TI - Cavitary osteomyelitis treated by fragmentary cortical bone transportation. AB - Fragmentary cortical bone transportation can be used to fill large gaps in chronic cavitary osteomyelitis when standard techniques have failed. A low-energy corticotomy can create a loose fragment of cortex with periosteal attachments and surface blood supply still intact. This "vital" fragment can be gradually pulled across a defect within a bone to restore the integrity of the bone segment by distraction osteogenesis. The biologic principles for successful distraction osteogenesis by this innovative technique are illustrated in a 41-year-old man with chronic cavitary (150 cc) (four years) osteomyelitis refractory to multiple debridements, Papineau grafting, gentamicin beads, and tricalcium phosphate. PMID- 1611738 TI - Onlay technique for occipitocervical fusion. AB - Twenty-eight occipitocervical fusions using the onlay technique were performed in 27 patients ranging in age from 13 to 77 years (average age, 47.6 years). The indications for fusion included neurologic involvement from atlantoaxial instability associated with superior migration of the odontoid and destructive changes at the occiput-C1-C2 articulation, causing pain unrelieved by conservative treatment. Preoperative diagnoses included rheumatoid arthritis, congenital anomalies, posttraumatic, failed C1-C2 fusions, ankylosing spondylitis, and tumor. A standard posterior exposure of occiput-C1-C2 was used, and iliac crest bone graft was placed over the area to be fused. Postoperative immobilization consisted of skull tong traction, minerva jacket, and halo apparatus. There were no neurologic complications, two superficial wound infections, and minor difficulties with halo loosening. There was one perioperative death. Primary fusion was obtained in 89% of patients at an average of 12.8 weeks. Occipitocervical fusion by the onlay technique is safe, requires no internal fixation, and has a high success rate when compared with other methods of obtaining fusion in the occipitocervical region. PMID- 1611737 TI - Ilizarov ankle arthrodesis. AB - Six consecutive patients, four with failed infected ankle fusions and two with posttraumatic degenerative ankle arthritis, were treated by monofocal compression arthrodesis using the Ilizarov external fixator. The average age was 48 years (range, 33-74 years). The average preoperative duration after failed infected ankle fusion was 18 months and for posttraumatic arthritis after fracture, 23 months. Infected failed pseudarthroses had significant fixed valgus deformity of the foot, bilateral draining sinuses, and near complete destruction and loss of the talus. Compression was dynamically applied during treatment. Custom foot plates were secured to the frame, and weight bearing as tolerated was allowed throughout the treatment period. Tibiocalcaneal fusion was obtained in three of four infected failed ankle fusions at an average of seven months (range, five to nine months). There was no evidence of infection at follow-up evaluation in these patients. One patient did not tolerate the frame and developed a fibroarthrosis. One patient sustained a refracture of the fusion at six months. Successful tibiocalcaneal fusion was obtained with reapplication of the frame and a Pappineau graft. Two primary ankle fusions healed with tibial talar fusion at an average of 3.5 months. Overall follow-up time averaged 26 months (range, 19-30 months). Six wires broke, requiring simple replacement. Four of these six were 1.5-mm wires. The Ilizarov frame may have several advantages in primary ankle arthrodesis and in the salvage of infected failed ankle fusions. PMID- 1611739 TI - Accessory head of the biceps brachii. Case report demonstrating clinical relevance. AB - Although anatomic variations in the origin of both the coracobrachialis or biceps brachii have been observed, there have been no previous reports of clinical relevance. In a 22-year-old man, recognition and mobilization of an accessory long head of the biceps brachii was necessary for adequate exposure of the shoulder joint dislocation through a deltopectoral incision. PMID- 1611740 TI - The anatomy and potential effects of contracture of the coracohumeral ligament. AB - In 63 anatomic specimens of the shoulder, the coracohumeral ligament was found to be a clear, well-developed structure in 59 and absent or vestigial in four. The origin of the coracohumeral ligament was consistently found at the base of the coracoid process. The insertion was more variable, between the rotator interval, supraspinatus, and subscapularis. In fresh specimens, the coracohumeral ligament was tight with maximal external rotation, which increased an average of 32 degrees on sectioning this ligament only. The coracohumeral ligament has been found to be shortened in various pathologic states. Its release may be required to restore restricted external motion when doing arthroplasties or to allow adequate mobilization of the tendons when repairing retracted tears of the rotator cuff. PMID- 1611741 TI - Elbow subluxation and dislocation. A spectrum of instability. AB - After sequential releases of the ligaments and capsules of 13 fresh autopsy specimen elbows, external rotation and valgus moments with axial forces resulted in posterior dislocations in 12 of the 13 with the anterior medical collateral ligament (AMCL) intact. Kinematic displacements measured with a three-dimensional electromagnetic tracking device showed that dislocation involved posterolateral rotation of 34 degrees-50 degrees and 5 degrees-23 degrees valgus at about 80 degrees flexion. Dislocation is the final of three sequential stages of elbow instability resulting from posterolateral rotation, with soft-tissue disruption progressing from lateral to medial. In each stage, the pathoanatomy correlated with the pattern and degree of instability. Testing for valgus stability of the elbow during simulated active flexion revealed no significant increase (-0.3 degrees-2.4 degrees) in valgus laxity after reduction compared with the intact specimens (p greater than 0.05, beta = 0.1, delta = 2.5 degrees). In no case did the digitized AMCL origin-to-insertion distance increase beyond normal during the dislocation (p less than 0.01). The mechanism of dislocation during a fall on the outstretched hand would involve the body "rotating internally" on the elbow, which experiences an external rotation/valgus moment as it flexes. Posterior dislocations should therefore be reduced in supination. If valgus stability in pronation is demonstrated, the AMCL can be assumed to be intact, and rehabilitation in a hinged cast-brace with the elbow in full pronation can be commenced immediately. PMID- 1611742 TI - Advantages of "epitenon first" suture placement technique in flexor tendon repair. AB - A carefully performed flexor tendon repair should not result in enlargement of the tenorrhaphy. However, many current repair techniques using a core suture followed by an epitendinous suture have this drawback. A technique of placing the epitenon suture first, followed by the core suture, is discussed, and the advantages of the technique are emphasized. PMID- 1611743 TI - Ilizarov method. PMID- 1611744 TI - Ilizarov method. PMID- 1611745 TI - Etiology of deep sepsis in total hip arthroplasty. The significance of hematogenous and recurrent infections. AB - Between January 1970 and August 1986, 3051 total hip arthroplasties (THAs) were performed at the authors' institution. Forty-seven hips in 43 patients developed deep infection. Using clinical and laboratory criteria, patients were classified into four modes of infection: (1) surgical contamination, which included hips (N = 13) with a suspicious clinical course (e.g., persistent elevation of sedimentation rate, early radiographic signs of loosening) without another identifiable source; (2) hematogenous spread, which included septic hips (N = 19) with a temporally related infectious source and an organism consistent with that source; (3) recurrent sepsis, septic failure in a previously infected hip (N = 13); and finally, (4) infection from direct or contiguous spread, which occurred in an additional two patients. Thus the majority of infections were nonsurgical. Patients with surgically acquired infections tended to present earlier, were less likely to require a Girdlestone procedure for salvage, and were more likely to be reimplanted (p = 0.024). The incidence of surgical infections decreased with the use of improved antiseptic techniques. The incidence of hematogenous infection, however, increased during the time that a cohort was followed. Additionally, in a previously septic hip, septic failure may occur as late as seven years after THA. PMID- 1611746 TI - Reduction of a nonconcentrically relocated hip dislocation in a seven-year-old boy. AB - Traumatic dislocation of the hip in childhood is a rare injury. Treatment usually consists of a closed reduction and some form of immobilization. Inability to obtain a concentric reduction by closed means is commonly attributable to soft tissue interposition. This is a report of a method not previously described for obtaining reduction of a nonconcentrically reduced traumatic hip dislocation without an open surgical procedure. PMID- 1611747 TI - Hip fracture mortality. A prospective, multifactorial study to predict and minimize death risk. AB - Four hundred consecutive hip fractures were studied prospectively. Two hundred forty-seven patients were classified as unhealthy (poor cardiac status, pneumonia, cancer history, bowel obstruction history, malnutrition, dehydration, stroke history, renal failure history, cirrhosis). Twenty-two percent of this unhealthy group died, while only 6% of the remaining healthy group died. Death rates varied with admission activity level and mental status but not when patient health status was factored out. After factoring out health status, age was associated with higher death rates only in patients older than age 85. Confusion, a change of mental status in the hospital, occurred in 25% of patients. Confusion was associated with a medical complication in 94% of cases, was the presenting symptom of a medical complication in 79% of cases, and was associated with a 39% death rate. Major medical complications occurred in 9% of the healthy group (29% of them died) and 21% of the unhealthy group (64% of them died). Major medical complications in unhealthy, shut-in patients were associated with an 80% death rate. Vigorous urinary tract monitoring and early treatment of bacteriuria decreased death rate. Postfracture malnutrition was associated with higher complication rates. Hip surgery performed within 72 hours on patients with acute medical illnesses in addition to their fracture was associated with a higher death rate. Whether a patient walked postfracture seemed not to be correlated with the death rate. Patients who were not walking prefracture but treated by internal fixation had a 34% failure rate. PMID- 1611748 TI - Magnetic resonance imaging in diagnosis of transient osteoporosis of the hip. AB - The results of magnetic resonance (MR) imaging in six patients with transient osteoporosis of the hip were reviewed. Short TR/TE (repetition time/echo time) images demonstrated diffusely decreased signal intensity in the femoral head and intracapsular region of the femoral neck. Increased signal intensity was noted with progressive T2 weighting. Bone biopsies were performed in four patients. Histologic findings were nonspecific and included fat necrosis, marrow edema, increased bone resorption, and reactive bone formation. Repeat MR scans in two patients, performed six and eight months after the initial scans, showed an almost complete return to normal marrow signal. All patients became asymptomatic without bony deformity. In the appropriate clinical setting, MR scanning can aid in the diagnosis of transient osteoporosis as the cause of a painful hip. PMID- 1611749 TI - Mechanical considerations in using tensioned wires in a transosseous external fixation system. AB - Factors that affect wire tension were examined using external mechanical testing units as well as in-line load cells. The circular external fixator with wires supported at each end exhibits a self-stiffening effect such that wire stiffness increases with wire deflection. Mechanical slippage between wire and fixation bolt is the primary reason for loss of wire tension. Slippage can be avoided by adequate torque on the fixation nut (20 N.m). Guidelines are presented for proper and safe tensioning techniques to achieve clinically indicated tensions without risk of breakage. PMID- 1611750 TI - Prophylaxis for heterotopic bone formation after total hip arthroplasty using low dose radiation in high-risk patients. AB - Fifteen consecutive total hip arthroplasties (THAs) in 14 patients considered at risk for developing significant heterotopic ossification (HO) were treated postoperatively with 7.5 Gy of external beam radiation in three fractions. Eight hips in eight of the patients (Group I) had developed previous Brooker Class III or IV HO after THA and were radiated after having excision of HO in conjunction with a revision THA. Three additional hips in three patients (Group II) were radiated after primary THA, because they developed significant HO on the contralateral hip after a previous THA. The remaining four hips in three patients (Group III) were radiated after primary THA because they had bilateral hypertrophic arthritis. Precision shielding was employed to minimize the volume of tissue in the radiation field and to protect the bone-implant interface around porous-coated components and the trochanteric osteotomy sites. Of the eight hips in which Class III or IV bone was excised during revision THA (Group I), no new bone formed in five hips and in the other three hips, only Class I bone formed. No heterotopic bone formed in the remaining seven hips of Groups II and III. All six trochanteric osteotomies healed. There were no wound healing problems. There were no significant radiolucencies around any of the components and there was no radiographic evidence of implant instability. This regimen using 7.5 Gy over three fractions minimizes the radiobiologic impact, whereas the use of precision shielding minimizes the total volume of tissue treated. This regimen is an effective means of preventing significant HO after THA in high-risk patients while minimizing radiation exposure. PMID- 1611751 TI - Rupture of the Achilles tendon in rheumatoid arthritis with histologic evidence of enthesitis. A case report. AB - Spontaneous Achilles tendon rupture occurred in a 60-year-old man with a two-year history of sero-positive rheumatoid arthritis (RA). Histologic section of the ruptured Achilles tendon revealed the existence of rheumatoid granulation that consisted of lymphocytes, histiocytes, and small vascular proliferation within the tendon tissue. The enthesis of the tendon to the calcaneus also revealed lymphocyte infiltration in the bone marrow and rheumatoid granulation within the tendon. Throughout the course of his disease, the patient had not been treated with corticosteroids. These facts suggested that enthesis (attachment of tendon to bone) was one of the extraarticular sites of the rheumatoid inflammation and that enthesitis was a possible cause of Achilles tendon rupture in this RA patient. PMID- 1611752 TI - A flap augmentation technique for Achilles tendon repair. Postoperative strength and functional outcome. AB - The efficacy of tendo-Achilles rupture repair by a modified version of Lindholm's technique was studied biomechanically and functionally. The procedure involves secondary reinforcement of a conventionally reapproximated rupture site by means of a backfolded augmentation flap. The flap cross section consisted of approximately one third of the proximal stump. In 18 paired fresh anatomic Achilles tendons, flap augmentation repairs had an average strength of 217.5 N (SD = 44.7), whereas conventional repairs (two interrupted Kessler sutures) failed at an average of 153.9 N (SD = 30.2). In a series of seven augmentation flap patients evaluated clinically and by Cybex dynamometry, an excellent result (by the Percy/Conochie rating) was obtained in six, and a good result in one. Plantar flexion strength in full extension averaged 94% of that of the uninvolved leg. There were no reruptures. These data suggest that flap augmentation may be a useful adjunct to conventional suture repair. PMID- 1611753 TI - An atypical case of deep vascular hamartomata. AB - A 17-year-old man who initially had an injury to the lower extremity was eventually diagnosed as an unusual case of deep vascular hamartomata. After initial treatment, the patient returned on numerous occasions with pain, swelling, and a cystic lesion of the leg. Despite operative excision of the lesion, which spread to the abdomen, it continually reappeared. Surgeons should be aware of hamartomata in patients with a warm, painful, swollen lower extremity. PMID- 1611754 TI - Hydatid bone disease of the pelvis. A report of two cases and review of the literature. AB - Hydatid disease is caused by a parasitic tapeworm Echinococcus. This parasite in larval stage can thrive in many parts of the body, most frequently in the liver. Hydatid disease in bone is rare, but in areas where hydatid disease is endemic, it must always be considered in the differential diagnosis. Two cases of hydatid bone disease of the pelvis are reported. The treatment of choice is a combination of chemotherapy and surgery. PMID- 1611755 TI - Hemangiomas of the long tubular bone. AB - The overall spectrum of hemangiomas involving long tubular bones is exemplified by three cases, the first being medullary, the second periosteal, and the third intracortical. The clinical presentation was progressive pain at the site of the lesion in all cases. The medullary hemangioma involved the distal shaft of the humerus and was entirely radiolucent. The periosteal tumor was exceptional in that it affected the proximal shaft of the tibia in contrast to the seven previously reported cases that involved the midshaft of the bone. The intracortical hemangioma was in the tibia, the site of all three previously reported cases. Hemangioma of bone may show variable roentgenographic patterns related to the anatomic location and the type of involved bone. The final diagnosis is dependent on histologic evaluation. PMID- 1611756 TI - Airport detection of modern orthopedic implant metals. AB - The sensitivity of airport metal detectors to a variety of orthopedic implants shows that total hip and total knee replacements, intramedullary nails, hip compression screws, and bone plates can escape detection. The metallurgic composition of the undetected implants were titanium, titanium-aluminum-vanadium alloy, cobalt-chrome-molybdenum alloy, and some stainless steel. The implants were tested individually, in combination, and as a whole in each of three different metal detectors. Only one of the screened implants activated a metal detector: an old Austin Moore straight fenestrated endoprosthesis that individually activated one of the three metal detectors. All of the other screened implants were not detected by any of the three tested metal detectors. Furthermore, the Moore endoprosthesis failed to activate two of the three tested metal detectors. Metal objects are identified by metal detectors based on their ferrous content. Contemporary orthopedic implants use little, if any, ferrous metal and therefore escape detection by airport metal detectors. PMID- 1611757 TI - Pycnodysostosis. Orthopedic aspects with a description of 14 new cases. AB - Pycnodysostosis is an uncommon form of osteosclerosing bone disease. The orthopedic aspects are illustrated by 14 new cases. PMID- 1611758 TI - Estrogen receptors in fracture healing. AB - Estrogen has profound effects on the regulation of bone metabolism, but its role in fracture healing is unknown. Several recent reports have documented the presence of estrogen receptors in vitro and in diseased tissue. The authors investigated estrogen receptors in nonneoplastic skeletal tissues by immunohistochemical and radioligand binding techniques. Using a fibular osteotomy model of fracture healing in New Zealand rabbits, radioligand binding detected specific, high affinity, saturable estradiol binding sites at low levels throughout fracture healing, with a trend towards a bimodal distribution. Peaks occurred three and 16 days after osteotomy. No estrogen receptor was found by either method in later fracture callus, growth plate, or periosteum. These findings suggest a possible role for estrogen in the early inductive phase and later phase of endochondral ossification in fracture healing. PMID- 1611759 TI - Osteomyelitis experimentally induced with Bacteroides thetaiotaomicron and Staphylococcus epidermidis. Influence of a foreign-body implant. AB - Experimental osteomyelitis was induced in the rabbit tibia with Staphylococcus epidermidis alone, with Bacteroides thetaiotaomicron alone, and with both bacteria as etiologic agents, in the presence or absence of a foreign-body implant. Animals were monitored by clinical observation and roentgenographic, microbiologic, histologic, immunofluorescent microscopic, and electron microscopic methods. Scanning and transmission electron microscopy showed masses of coccoid and rod-shaped bacteria embedded in a matrix of exopolysaccharide and adhered to bone, marrow, and the foreign-body implant (when present). Of the 58 rabbits receiving an implant, osteomyelitis developed in 48 (83%), and bacteria were recovered by culture from 56 (97%). Of the 31 animals without the implant, osteomyelitis developed in 18 (58%), but no bacteria were recovered by culture. Bacterial recovery appeared to be dependent on the presence of the implant. The rate of induction and the severity of osteomyelitis were enhanced by the presence of the foreign-body implant and by the polymicrobic infection. PMID- 1611760 TI - A new canine cruciate ligament formed through distraction histogenesis. Report of a pilot study. AB - A modified Ilizarov external fixator was used to transfix the stifle joint in 13 dogs. A 1-cm cortical cancellous bone plug was outlined in the intracondylar notch of the femur after excising the anterior (cranial) cruciate ligament (ACL). Hardware attached to the plug allowed controlled distraction of the plug into a cut tibial channel trailing the regenerate ligament. No attempt was made to exactly recreate the normal anatomic course of the ACL. Some bone plugs became dislodged from the femur before distraction began, while others consolidated prematurely. These specimens produced scar only and served as a control group against which the regenerate ligament and normal ACLs were contrasted biomechanically, biochemically, and histologically. The dogs were killed at intervals from four to 21 weeks postoperatively. Load to failure at 21 weeks reached 71% of the mean normal. Histologic examination showed an improved fiber organization of the regenerate compared with the scar group. The regenerate and scar groups showed increased percent water compared with normal, while there was no significant difference in percent collagen and glycosaminoglycan content. PMID- 1611762 TI - A potential devastating complication of any impingement or rotator cuff surgery. PMID- 1611761 TI - Porous-coated uncemented components in experimental total hip arthroplasty in dogs. Effect of plasma-sprayed calcium phosphate coatings on bone ingrowth. AB - The effect of a thin plasma-sprayed, calcium phosphate ceramic coating on bone ingrowth into titanium fiber mesh porous-surfaced prostheses was examined in a controlled canine cementless total hip arthroplasty model. Bone ingrowth was quantified using backscattered scanning electron microscopy of undemineralized sections. When good contact between the bone and porous coating was present, the calcium phosphate-coated prostheses contained significantly higher amounts of bone ingrowth at three weeks postimplantation than the uncoated control prostheses. At six weeks, however, there was no significant difference in the amount of bone ingrowth between the coated prostheses and uncoated prostheses. The ingrown bone seemed to be more intimately associated with the calcium phosphate-coated porous surfaces than the uncoated porous surfaces. When gaps at the bone-porous coating interface occurred, the calcium phosphate coating did not enhance bone ingrowth across those gaps. Plasma-sprayed calcium phosphate coatings may be useful in enhancing the early ingrowth of bone into porous surfaced joint replacement prostheses, but they may lack long-term effectiveness. The coatings were not effective in enhancing bone ingrowth across gaps between the porous surface and the bone bed prepared at surgery. PMID- 1611763 TI - Corticotomy. AB - A correctly performed corticotomy is essential to the success of distraction osteogenesis and prepares for deformity correction, limb lengthening, elimination of bone and soft-tissue defects, reshaping of bones, and treatment of cavitary osteomyelitis. The modern corticotomy has evolved from the initial open osteotomies, which eventually proved to be traumatic to bone's osteogenic elements, and closed bone osteoclasis, which proved time consuming and difficult to control. Ultimately, this led to the combination of an open partial subperiosteal cortical osteotomy, followed by manual osteoclasis of the remainder of the bone cortex. The various types of corticotomy, each with its own special purpose, include transverse or oblique, longitudinal, "splinter," and partial. The techniques and indications for each are outlined. Consideration is given to the latency period--the time from corticotomy to onset of distraction. Morphologic studies have shown that optimally this period should be from seven to ten days. The complications of corticotomy include damage to the osteogenic elements through rough surgical technique, displacement of the fragments after corticotomy, and incomplete corticotomy. PMID- 1611764 TI - Mechanical axis deviation of the lower limbs. Preoperative planning of uniapical angular deformities of the tibia or femur. AB - Angular deformities of the tibia or femur in the frontal plane lead to mechanical axis deviation of the lower limb and malorientation of the joints above and below the level of deformity. Accurate correction of the malalignment and of the joint orientation is important for function and to prevent joint degeneration. An accurate yet simple method to determine the apex of deformity and the type of correction required is based on the joint reference lines of the hip, knee, and ankle, and the individual mechanical axis lines of each bone segment. If the osteotomy is performed at the level of the apex of the deformity, then the only correction needed is angulation. If the osteotomy is performed at a level proximal or distal to the apex, then translation in addition to angulation is necessary to accurately correct the deformity. PMID- 1611765 TI - Mechanical axis deviation of the lower limbs. Preoperative planning of multiapical frontal plane angular and bowing deformities of the femur and tibia. AB - Multiapical deformities complicate the process of preoperative planning. It is necessary to determine the level of each apex of deformity to plan accurate correction. The basic principles of mechanical axis realignment and joint orientation need to be preserved. Using the joint reference lines and mechanical axis of each bone segment, one can accurately determine the apex of each deformity. Bowing deformities are multiapical angular deformities. There are two types of bowing deformities: compensated and noncompensated. Typical examples of compensated bowing are the anterolateral and posteromedial bows of the tibia. A noncompensated bow is typical of the deformity seen in rickets. PMID- 1611766 TI - The replacement of long tubular bone defects by lengthening distraction osteotomy of one of the fragments. 1969. PMID- 1611767 TI - Pediatric applications of the Ilizarov method. AB - Since mid-1987, more than 250 applications of the Ilizarov technique have been successful in treating a variety of pediatric orthopedic problems. The principles of the method are the same in adults and children. Careful preoperative planning and close follow-up evaluation during distraction are important to success. Complication rates are high but improving as experience is gained with the technique. Most complications can be managed such that the ultimate success is not jeopardized. The Ilizarov technique has wide application in the treatment of difficult deformities. The method is useful for treatment of limb-length discrepancy projected to be greater than 5 cm and in limb-length discrepancy combined with angular deformity. The method is applicable to angular deformities such as in adolescent Blount's disease and congenital tibial pseudarthrosis, especially conditions where bone transport may be needed to gain length. In resistant or recurrent clubfeet, the Ilizarov technique is useful as an alternative to osteotomy of the mid- and hindfoot or both. The method may even be indicated for lengthening limbs in selected patients with short stature. PMID- 1611768 TI - Treatment of congenital pseudoarthrosis of the tibia using the Ilizarov technique. AB - The principle of treatment of congenital pseudoarthrosis of the tibia (CPT) with the Ilizarov method corrects all angular deformity and maximizes the cross sectional area of union of the pseudoarthrosis. Fifteen patients with a total of 16 CPT were treated using the Ilizarov apparatus. Various forces were used to treat the pseudoarthrosis site including compression, distraction, open reduction, resection and shortening, resection and bone transport, and invagination of one end in the other. Lengthening was performed in 12 of the 16. Deformity was corrected in all cases. The union rate was 94% with one treatment and 100% with two treatments. There were five refractures, three early and two late. Previous pin sites, residual angular deformity, and natural history were considered predisposing factors for refractures. One patient refractured twice but remained ununited. Fifteen remained united, with a mean follow-up period of four years (range, two to seven). There were two residual deformities, one in the regenerate and one at the level of the CPT. PMID- 1611769 TI - The Ilizarov technique in correction of complex foot deformities. AB - The Ilizarov technique allows new histogenesis of soft tissue as well as bone. This process, extended to the foot, has allowed correction of complex three dimensional deformities. The method is described and demonstrated to illustrate the action and limitations as well as the complications of the method. PMID- 1611770 TI - [Myasthenia gravis and steroid therapy]. AB - In the past 20 years, we experienced 242 myasthenic patients in our hospital. Fifty five cases were administered high doses of adrenocorticosteroid hormone for a long time. Among them, we analysed 39 cases with complete clinical records from admission to the present. We analysed 5 additional cases in whom responses to the therapy somewhat unique in that four cases have not shown any improvement until the drug was reduced to certain dosages, and in the 5th case change of method from alternate-day to every day brought good recovery of the symptoms. As a result, adrenocorticosteroid hormone was effective for 100% of the patients in this series. However, complete remission appeared in the above mentioned 10 patients (26%), after 2-3 years' continuous administration. Prognosis was far better in those who showed shorter durations between the onset of the disease and thymectomy or thymectomy than in those of longer one. In these cases, the maximum daily doses were 60-100 mg in alternate-day administration, and the total amount of prednisolone was 9-15 g in individual cases. Through data of these cases, it is recommended that the maximum dosage is to be continued for as long as 2 to 19 weeks with average 7 weeks. PMID- 1611771 TI - [Early-onset benign autosomal dominant limb-girdle myopathy with contractures (Bethlem myopathy) in a Japanese family]. AB - We report a family showing an early-onset benign autosomal dominant limb-girdle myopathy with contractures. The clinical features in our family included; 1) slowly progressive limb-girdle muscle weakness since childhood. 2) contractures of fingers, elbows and ankles, 3) mild motor impairment with preserved activities of daily living. The disease was inherited through an autosomal dominant trait. Muscle pathology revealed variation in fiber size, slightly increased central nuclei, mild endomysial fibrosis, type 1 fiber predominance and type 2 fiber atrophy. The above clinical features were similar to those seen in patients reported by Bethlem (1976) and Mohire (1988), and therefore we made a diagnosis of Bethlem myopathy on this familial patients which was extremely rare in Japan. PMID- 1611772 TI - [Detection of interferon-gamma and IL-6 producing cells in cerebrospinal fluid cells in the central nervous system infectious diseases using immunocytochemistry]. AB - To evaluate the relationship between cytokines and cerebrospinal fluid (CSF) cells, we detected interferon (IFN)-gamma and interleukin (IL)-6 producing cells in CSF from the patients with central nervous system (CNS) infectious diseases by immunocytochemistry. Five CSF cell smears from three herpes encephalitis patients, three from a patient with EB virus radiculoneuritis, four from the three patients with purulent meningitis, five from five patients with viral meningitis were obtained during early or subacute stages of diseases. Control CSF cell smears were taken from twenty seven patients with motor neuron disease, Parkinson's disease and spinocerebellar degeneration. Immunocytochemistry using specific polyclonal anti-IFN-gamma and IL-6 sera were used to detect each producing cell. Simultaneously, individual positively immuno-reactive cells were morphologically classified macrophage or lymphocyte. The IFN-gamma positive cells immunostained with specific antibody showed brown-colored deposits within the cytoplasm whereas no deposit was in the nucleus (Fig. 1). These phenotype of IFN gamma positive cells were considered to be lymphocytes or macrophages. However, IFN-gamma-positive macrophages were predominantly seen at the early stages of herpes simplex encephalitis and purulent meningitis. The percent of IFN-gamma positive cells in total CSF cells obtained from the patients with the CNS infectious diseases was 2.3-38.7 as shown in Table 1. The IL-6 positive cells (Fig. 2) were also found early in the course and in subacute stages in the CNS infectious diseases and ranged from 2.5-50 percent in total CSF cells (Table 1). In contrast neither IFN-gamma- nor IL-6-positive cells were detected in non inflammatory diseases (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611773 TI - [Vascular pathology in chronic progressive external ophthalmoplegia with ragged red fibers]. AB - Vascular involvement in biopsied muscle specimens from 11 patients with chronic progressive external ophthalmoplegia (CPEO) with ragged-red fibers (RRF) was studied. Almost none of 69 intramuscular arteries examined were strongly stained with succinate dehydrogenase (SDH) except one patient who had 2 SSV (strongly SDH reactive blood vessels) in his muscle biopsy. Although RRF and focal cytochrome c oxidase (CCO) deficiency in muscle fibers were the common histochemical changes in muscle biopsy specimens from CPEO patients, all mitochondria in both endothelial and smooth muscle cells of the arteries had normal morphology except for the two SSV and all mitochondria in the blood vessels had normal CCO activity by electron cytochemistry. The findings obtained from the present study were quite different from those in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and myoclonus epilepsy associated with ragged-red fibers (MERRF) in which the striking vascular involvement with SSV is the most common and major abnormality in muscle biopsy specimens. To study vascular involvement in mitochondrial encephalomyopathies is the one of very important clues to understand the pathophysiology of phenotypic expressions in mitochondrial encephalomyopathies. PMID- 1611774 TI - [Silent intracerebral lesions identified on magnetic resonance imaging in patients presenting with initial stroke--comparative studies of the affected hemisphere and the contralateral one]. AB - Among patients who had undergone MRI examinations with a clinical suspicion of stroke, we selected 82 patients with initial cerebral infarction being located only in a unilateral cerebral hemisphere. Seventeen (21%) subjects had wedge shaped lesions including cerebral cortex (the cortical type), 65 (79%) had them predominantly in white matter and/or territory of the deep perforators (the subcortical type). Fifty nine cases out of total 82 (72%:9 in the cortical type, 50 in the subcortical type) had the silent cerebral infarction in the contralateral hemisphere to the affected side found on the 1.5 tesla superconductive system T2 weighted magnetic resonance imaging. Among them, 57 had the contralateral small cortical and/or subcortical (white matter) infarction, the other 2 cases had the contralateral lacunar infarction in the basal ganglia internal capsule area as the silent lesion. The incidence of the cortical type was high in cases without the silent cerebral infarction in the contralateral hemisphere. It might be suspected that the cortical type had tendency to present clinical symptoms caused by initial stroke without prior silent cerebral infarction. The author proposed that the cerebral embolism might play an important role in showing the sudden onset clinical symptoms of the cortical type. And the author also proposed that there might be a difference in the development of clinical symptoms between the silent cerebral infarction located in the basal ganglia-internal capsule area and the cortical-subcortical (white matter) area. PMID- 1611775 TI - [Efficacy and limitations of antiepileptic drug monotherapy for temporal lobe epilepsy]. AB - To evaluate the efficacy of antiepileptic drug (AED) monotherapy, we studied 147 patients with temporal lobe epilepsy (TLE) aged 15 or older who had been undergoing treatment at our hospital for at least five consecutive years. We divided the treatment time into Period I which included one year beginning six months after the initial diagnosis, and Period II which was the two years from January, 1987 to December, 1989. The efficacy of therapy was evaluated for the two periods based on the following standards: effective, if seizures had been controlled, and ineffective, if at least one seizure had occurred during each period. Patients in whom monotherapy was effective increased by a factor of 1.7 over the period of observation, from 38 cases (28%) in Period I to 65 cases (44%) in Period II. The total number of effectively treated cases (including those on polytherapy) also rose from 58 cases (40%) in Period I to 79 cases (54%) in Period II. The average number of AEDs used was reduced from 3.0 +/- 1.3 at the time of initial diagnosis to 1.8 +/- 0.8 in Period I and 1.6 +/- 0.8 in Period II. When compared with the 68 ineffectively treated cases, significant background factors for the 65 effectively treated cases on monotherapy included: higher age at ictal onset, fewer histories of any previous treatment at initial diagnosis, or of encephalitis or febrile seizures, fewer psychological impairments such as cognitive degeneration or personality disorders, lower frequency of seizures, fewer histories of secondary generalization or automatism, and a higher rate of normal findings of background EEG and cerebral CT.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611777 TI - [Serial changes of magnetic resonance imagings in acute disseminated encephalomyelitis]. AB - We reported serial changes of MRIs in a case of acute disseminated encephalomyelitis (ADEM). On November 1, 1990, a previously healthy 73-year-old man had a grand mal seizure following myoclonic jerks of the right arm for six days. On admission, he was drowsy and presented with right facial palsy and incomplete tetraparesis. He became coma on the next day of admission. There was moderate leukocytosis. A spinal tap showed a normal opening pressure, 2 white blood cells/mm3, a total protein of 84 mg/dl, glucose of 89 mg/dl. CSF IgG (6.2 mg/dl) and myelin basic protein (6.7 ng/dl) were slightly increased. Serological examinations for virus titer were all negative. A CT scan on the 2nd day showed no abnormal findings, but MRI revealed small high intensity areas in the left thalamus, left prefrontal gyrus and right corona radiata, internal capsule on both the T2-weighted and proton density sequences. An MRI on the 14th day showed high intensity signals in the white matter of the bilateral frontal lobes, left operculum and right corona radiata. In contrast, the left thalamic lesion became smaller and less conspicuous than on the initial scans, but was enhanced with Gd on the T1-weighted sequences. Our findings indicate that MRIs are valuable in detecting pathophysiological changes of ADEM from the acute to chronic phases. PMID- 1611776 TI - [Shy-Drager syndrome and the syndrome of inappropriate secretion of antidiuretic hormone]. AB - We report a 52-year-old male patient with Shy-Drager syndrome (SDS) complicated by an occurrence of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The patient first developed impotence at the age of 48, accompanied by urinary incontinence, and episodes of dizziness while standing. The following year, the patient had developed a staggering gait and speech became monotonous. At age 52, the patient was admitted to the hospital after experiencing frequent episodes of syncope associated with complete loss of consciousness. Upon examination, blood pressure was 100/70 in a recumbent position, and 80/60 when standing. The pulse rate varied from 60 per minute to 62. The patient was alert. The alternating Horner sign was observed, and a paucity of facial movements was visible. His speech was slow and monotonous. Muscle tone was increased bilaterally. There was incoordination. A laboratory examination revealed reduced serum sodium levels of 127 mEq/L and increased sodium excretion with plasma hypoosmolality (262 mOsm/kg/H), urine hyperosmolality and low serum renin activity (0.2 ng/ml/h). Renal functions were normal and the levels of adrenocortical and thyroid hormones were normal. There were no abnormalities observed in the chest roentgenogram taken. The level of antidiuretic hormone (ADH) was unreasonably high (5.74 pg/ml). A water-load test demonstrated failure of both water diuresis and inhibition of ADH secretion. These data suggested that hyponatremia in this case was caused by SIADH. The correlation between plasma osmolality and the concentration of ADH suggested that osmolality that initiates ADH release appeared to have been reset to around 230 mOsm/kg lower than normal.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611779 TI - [Isolated angiitis of the CNS associated with Hashimoto's disease]. AB - In 1987, a 69-year-old female suffering from epilepsy and right hemiparesis was admitted to the hospital and given conservative therapy. During the next three weeks she became a stuporous state. Steroids were then prescribed, and she made a complete recovery. Following hormonal and immunological investigations, a diagnosis of Hashimoto's disease with hypothyroidism was made. Following her discharge, thyroxin and anticonvulsant treatments continued. On May 30, 1989, at the age of seventy-one, the patient was found lying unconscious at home, and taken to our hospital. She had signs of a confused state, and seizures of her right arm on admission. Cranial computed tomography (CT) revealed a low density area in the left parieto-occipital lobe, which was heterogeneously enhanced by contrast medium. Magnetic resonance imaging (MRI) showed a lesion of low signal intensity in T1-weighted images and high signal intensity in T2-weighted images, which was homogeneously enhanced by Gd DTPA. Cerebral angiography disclosed no abnormality. Two weeks later, follow-up CT showed that the lesion had become larger and markedly enhanced. A brain tumor, probably malignant lymphoma, was suspected. On June 14, stereotaxic biopsy of the enhanced lesion was performed. Histopathological examination disclosed dense infiltration of the entire walls of many small parenchymal vessels, both arterioles and venules, by lymphocytes. Treatment for angiitis (betamethasone 16 mg daily) was started on June 20, then gradually tapered, and the lesion diminished on CT. Our case has some features of both isolated angiitis of the central nervous system and encephalopathy in compensated Hashimoto's disease. It is suggested that some common base of the autoimmune diseases exists in this case. PMID- 1611778 TI - [Acute relapsing Guillain-Barre syndrome after 5 and 7 years asymptomatic intervals]. AB - A 26-year-old man who recovered from an initial episode of Guillain-Barre syndrome had two relapses after 5 years and then again after 7 years of asymptomatic intervals. The antecedent illnesses, distribution of weakness and clinical courses of each relapse were similar to each other, and each episode reached its peak within 10 days. He received different types of therapy on each time; gammaglobulin and steroid treatment, steroid monotherapy and plasma exchanges. Plasma exchanges were thought to be the most effective. Serum testing by enzyme-linked immunosorbent assay revealed that the patient contained high titer of IgG antibodies against GD1a and GT1b gangliosides and low titer of those against GM1 and GD1b, which were reduced during his clinical improvement. PMID- 1611780 TI - [Cerebellar ataxia with hypogonadotropic hypogonadism]. AB - A 38-year-old male began to develop progressive difficulty in speaking and walking in his early thirties. He was the younger of four siblings from the parents of consanguineous marriage. Allegedly, his brother had showed similar symptoms. On examination, he was sexually underdeveloped with absent facial and public hair as well as small firm testes. He showed typical eunuchoid habitus. Neurologically, his gait was markedly ataxic and speech was explosive. He was mildly demented (verbal IQ = 66) and eupholic. Generalized hyperreflexia and positive Babinski were observed. There were no signs of extrapyramidal, autonomic or peripheral nerve involvement. Laboratory data were remarkable for low level of serum gonadotropins and low level of HVA and 5-HIAA in CSF. Plasma long-chain fatty acids were normal and lysosomal enzymes in leukocyte including ASA showed no significant change. EEG showed diffuse slow activities with spikes on photic stimulation. The endocrinological studies including insulin-induced hypoglycemia and TRH test demonstrated hypothalamus-pituitary axis dysfunction. GH-RH test showed delayed response of GH secretion, suggesting the presence of hypothalamic disturbance. Brain CT showed cerebellar atrophy and symmetrical low density area in the cerebral white matter. On MRI, T2 weighed image showed diffuse and symmetrical high intensity area in the cerebral white matter. High signal intensities were also noted in the bilateral thalamus and pons. It is suggested that both hypogonadotropic hypogonadism and cerebellar ataxia in this disease may have a common underlying pathology of white matter. PMID- 1611781 TI - [Pathogenesis of juvenile muscular atrophy of unilateral upper extremity in reference to venous congestion of epidural space]. AB - MRI and dynamic CT studies were performed in a young male with juvenile muscular atrophy of unilateral upper extremity (JM) with onset at age 15 and clinical course of 2 years. The mechanism of development of congestion in vertebral venous plexus was considered. Dynamic CT of the head in the neck flexion showed rapid reflux of blood from the intervertebral veins into the posterior internal vertebral venous plexus at the C5-C6 level and consequent congestion. It is speculated that in this patient some mechanism associated with head anteflexion led to a reflux into the valveless posterior internal vertebral venous plexus and congestion as well. Furthermore, it could be considered that anterior shift of the dural sac at the time of head anteflexion plays an important role in the development of this internal vertebral venous plexus congestion in JM. PMID- 1611782 TI - [A case of portal-systemic encephalopathy presenting characteristic MR images in globus pallidus, hypothalamus, corpus callosum, pontine base, and middle cerebellar peduncle]. AB - A 53-year-old woman developed symptoms of slow speech, mild dementia, increased deep tendon reflex, ataxic gait, flapping tremor, and dystonic posture during two years. She had liver cirrhosis and hyperammonemia, which suggested a diagnosis of portal-systemic encephalopathy. MR T1-weighted images showed increased signal intensity in globus pallidus, internal capsule, substantia innominata, and a part of hypothalamus. T2-weighted images revealed abnormal findings as follows: high intense area in middle cerebellar peduncle, and low signal intensity of corpus callosum and pontine base. This is the first report about MRI abnormalities in substantia innominata, corpus callosum, and pontine base in a patient with portal systemic encephalopathy. PMID- 1611783 TI - [Sphenoid sinus mucocele with recurrent visual disturbance]. AB - We presented a case with sphenoid sinus mucocele associated with recurrent visual disturbance on the same side. A 22-year-old female showed two episodes of visual disturbance on the left eye for three months. She was diagnosed as acute retrobulbar optic neuritis and was treated with cortico-steroid. In two episodes visual disturbance improved in a week. MRI showed a mucocele in the left sphenoid sinus. No destruction of left optic canal was found in roentgenogram and the left optic nerve showed swelling with high intensity in T2-weighted MRI. Therefore the expansion of inflammation or edema in optic canal rather than direct compression by expanding mucocele was considered as pathogenesis of the visual disturbance. In a case of recurrent and unilateral visual disturbance, a mucocele of posterior paranasal sinus should be suspected in the differential diagnosis. PMID- 1611784 TI - I-123 MIBG and serial radionuclide angiocardiography in doxorubicin-related cardiotoxicity. AB - In six patients with doxorubicin-related cardiotoxicity, the severity of decrease in left ventricle ejection fraction (LVEF) was associated with faster myocardial I-123 MIBG washout rates. In four patients with severely decreased LVEF (range 19% to 28%), the 4-hour washout rate varied from 43% to 56%. In two patients with moderate cardiotoxicity (LVEF 42% and 43%), the washout rates were 37% and 35%, respectively. In contrast, in another patient thought to have initial left ventricular dysfunction (LVEF dropped from 66% to 54%), the myocardial I-123 MIBG retention rate was not reduced (6% washout). Subsequent continuation of chemotherapy in this patient was without complication. Reduced I-123 MIBG uptake in the left ventricle generally correlated with areas with abnormal Fourier amplitude values, but in one of the patients with moderate cardiotoxicity, the I 123 MIBG uptake was not reduced in a region with loss of amplitude, indicating dysfunction but probably no myocardial denervation. Analysis of the regional myocardial retention in patients with cardiotoxicity showed no significant difference in the I-123 MIBG washout rates of both segments with or without loss of amplitude. These data suggest that in spite of a localized loss of ventricular function demonstrated by radionuclide angiocardiography, doxorubicin-related cardiotoxicity appears to be based on a global process of myocardial adrenergic derangement. PMID- 1611785 TI - Clinical experience with Tc-99m MIBI imaging in patients with malignant tumors. Preliminary results and comparison with Tl-201. AB - Tc-99m MIBI imaging was performed in 34 patients with histopathologically proven malignant tumors. The study was performed in two steps. In the first step, only Tc-99m MIBI imaging was performed (Group 1). In the second step, both Tc-99m MIBI and Tl-201 imaging were performed for comparison (Group 2). Seventeen patients were studied in each step. The size of the smallest primary tumor (breast cancer) was 15 x 10 mm, and that of the largest (lung cancer) was 145 x 130 mm. Of the 34 patients, 26 showed Tc-99m MIBI uptake at the tumor site. In Group 1, 12 patients showed Tc-99m MIBI tumor uptake, but no uptake was detected in five patients (squamous cell carcinoma of the esophagus, teratoma of the testis, nonHodgkin's lymphoma, and squamous cell carcinoma of the lung). In Group 2, 13 patients showed both Tc-99m MIBI and Tl-201 uptake at the tumor site, but one patient with breast cancer showed only Tc-99m MIBI uptake, and three patients showed no Tc-99m MIBI and Tl-201 uptake (embryonal cell carcinoma of the testis, hepatocellular carcinoma). The overall sensitivity of Tc-99m MIBI imaging was 76.4%. In Group 2, the sensitivity was 82.3% for Tc-99m MIBI and 76.4% for Tl-201. Our preliminary clinical experience suggests that Tc-99m MIBI can be helpful in localizing malignant tumors and that its sensitivity is slightly higher than Tl-201. PMID- 1611786 TI - Anomalous origin of the left coronary artery. Use of thallium perfusion scans in the evaluation of successful revascularization. AB - Thallium imaging was performed on a 2-month-old infant with a left coronary artery originating from the pulmonary artery. Imaging was performed before and after corrective surgery, which involved creating a new left coronary osteum from the ascending aorta. The radionuclide study documented successful revascularization postoperatively. PMID- 1611787 TI - Detection of recurrent colon cancer with In-111 labeled MoAb B72.3 in a patient with normal CEA and TAG-72 levels. AB - The usefulness of radioimmunoscintigraphy with In-111 labeled MoAb B72.3 is illustrated in this case report of a patient with an aggressive cancer of the ascending colon. When used in conjunction with CT, ultrasound examination, and MRI, radioimmunoscintigraphy improved the specificity of these other imaging modalities, although the patient's serum CEA and TAG-72 levels remained within the normal ranges. In addition, MoAb imaging demonstrated superiority over CT in identifying an additional unsuspected lesion. Detection of occult disease by imaging modalities with or without elevated serum CEA levels is discussed. PMID- 1611788 TI - Tc-99m HMPAO labeled WBC scan for the detection of myocarditis in different phases of Kawasaki disease. AB - Myocardial imaging with Tc-99m HMPAO WBC was used to detect myocarditis of Kawasaki disease in 103 infants and children (66 boys and 37 girls, mean age 3 years and 4 months). The clinical course of Kawasaki disease may be divided into three phases, from the onset of illness onset until all clinical symptoms and signs have disappeared. Twenty-four hour myocardial imaging was performed in anterior, LAO, and left lateral views. The grading system was as follows: score 0 less than bone uptake; 1 = bone uptake; 2 greater than bone uptake; and 3 greater than or equal to liver uptake. If the score was greater than or equal to 2, significant myocarditis was considered. The appearing ratio of myocarditis was 57% (13/23) in the first phase; 65% (15/23) in the second phase; 54% (31/57) in the third phase. No significant difference was demonstrated among the three groups of patients (P greater than 0.1, by Chi-square test). In conclusion, an occult myocarditis may continue in all three phases of Kawasaki disease, even if the clinical symptoms and signs had improved by the evidence of Tc-99m HMPAO labeled WBC scan to avoid advanced cardiac complication. PMID- 1611789 TI - Noninvasive assessment of myocardium at risk by Tl-201 SPECT imaging in a child with Kawasaki disease. A case report. AB - Serial two-dimensional echocardiograms documented the formation of giant aneurysms, measuring from 0.55 to 3.1 cm in diameter, in the distribution of the left and right coronary arteries, in a 2 1/2-year-old boy with Kawasaki disease. His global left ventricular function, assessed by M-mode echocardiography, was normal, and no significant wall motion abnormalities could be detected on two dimensinal evaluation. Cardiac catheterization showed multiple aneurysms with no evidence of stenosis. Although he had no clinical symptoms or electrocardiographic evidence of ischemia, pharmacologic stress and delayed Tl 201 SPECT images revealed prominent stress-induced myocardial ischemia in the left ventricle. A resting gated blood pool study showed hypokinesia in corresponding regions of the left ventricle. This case demonstrates the usefulness of Tl-201 myocardial SPECT imaging and resting gated blood pool studies in the management of coronary artery disease in children with Kawasaki disease. PMID- 1611790 TI - Estimation of the effect of a preinjection of Tc-99m MDP on lumbar spine bone mineral density determinations. PMID- 1611791 TI - Unusual clinical presentation and scintigraphic pattern in myositis ossificans. AB - Myositis ossificans, or heterotopic bone formation, is a possible sequela of musculoskeletal trauma. Its radiographic and scintigraphic appearances have been well documented. Specifically, plain film radiographs usually show soft tissue calcification in the muscle groups adjacent to the trauma. The three-phase bone scan may demonstrate an area of nonspecific increased tracer uptake in all three phases. The authors present a case of radiographically demonstrated heterotopic bone formation in the leg of a retired football player. PMID- 1611792 TI - Bone and gallium scintigraphy in sacral chordoma. Report of four cases. AB - Bone scintigraphy with Tc-99m HMDP and gallium scintigraphy were evaluated in four patients with a primary sacrococcygeal chordoma. All lesions showed a photon deficient or cold lesion corresponding to the tumor on bone scintigraphy, with no abnormal accumulation clearly observed on gallium scintigraphy. These findings led the authors to conclude that a midline sacrococcygeal tumor showing reduced uptake or a cold lesion on bone scintigraphy and no increased accumulation on gallium scintigraphy could be a chordoma rather than the malignant neoplasm suspected in this region. PMID- 1611793 TI - Breast uptake of Ga-67 in a neonate. AB - A 6-day-old baby boy showed concentration of Ga-67 citrate in both breasts and an abdominal neuroblastoma. The breast uptake was most likely caused by estrogen and prolactin production and passage from the maternal to the fetal circulation. PMID- 1611794 TI - Preliminary report of SPECT imaging with Tc-99m teboroxime in ischemic heart disease. AB - Tc-99m teboroxime (Cardiotec) is one member of a new class of radiopharmaceuticals, the BATO agents (boronic acid adducts of technetium dioxime). This agent is a small, neutral, lipophilic compound with a high myocardial extraction (approximately 85% to 90%), and its uptake in the heart is directly related to myocardial perfusion. Tc-99m teboroxime washes out rapidly from the heart, and its potential for SPECT imaging has therefore been questioned. Tc-99m teboroxime SPECT imaging was compared prospectively with thallium SPECT (20 of 20 patients) and coronary arteriography (17 of 20 patients) suspected of having coronary artery disease. In this small preliminary series, both Tc-99m teboroxime and thallium SPECT detected all abnormal patients (12 of 12) and predicted correctly the site of critical stenosis in 20 of 24 diseased arteries (83%). Tc-99m teboroxime SPECT was normal in 5 of 6 patients without evidence of disease. Several cases occurred of clearly different radiotracer distribution (not related to obvious artifacts) with teboroxime compared with thallium, and lesion size was significantly larger on teboroxime compared with thallium SPECT. The clinical significance of these differences is not yet clear. Tc-99m teboroxime SPECT is possible with imaging times less than half those of thallium SPECT. Though much work remains to be done, teboroxime, because of its unique kinetics, creates many new possibilities for the evaluation of ischemic heart disease. PMID- 1611795 TI - "Speckled" radiogallium images in disseminated Mycobacterium fortuitum skin infection. PMID- 1611796 TI - Esthesioneuroblastoma demonstrated on bone scan. Correlation with CT and MRI. PMID- 1611797 TI - Scintigraphic demonstration of jugular obstruction in a case of Lemierre syndrome. PMID- 1611798 TI - Tc-99m HMDP uptake by the kidney in sickle cell disease. PMID- 1611799 TI - Gallium-positive thrombophlebitis. PMID- 1611800 TI - Potential false-positive In-111 labeled leukocyte study in a patient with orthopedic hip arthroplasty. PMID- 1611801 TI - Bone scan images of a giant chondrosarcoma. PMID- 1611802 TI - False-positive I-131 scan induced by Zenker's diverticulum. PMID- 1611803 TI - Hepatobiliary imaging in acute alcoholic hepatitis with fatty liver. PMID- 1611805 TI - Mechanisms of the stereoselective interaction between miconazole and racemic warfarin in human subjects. AB - Miconazole decreased the total body clearance of both (R)- and (S)-warfarin in normal subjects but did not change volumes of distribution. Miconazole inhibited the oxidation of both (R)- and (S)-warfarin to phenolic metabolites, although (S) warfarin was inhibited to the greater extent. In particular, (S)-7-hydroxylation, the pathway primarily responsible for termination of the anticoagulant effect, was most strongly inhibited. Inhibition of warfarin hydroxylation by miconazole in human liver microsomes and the in vivo results showed a good rank order correlation. The enhanced anticoagulant effect observed when miconazole and warfarin are coadministered may result from inhibition of P4502C9, the isozyme of P450 primarily responsible for the conversion of (S)-warfarin to (S)-7-hydroxy warfarin. Because miconazole inhibits a number of P450 isozymes, in addition to P4502C9, it can be expected to lead to interactions with other drugs whose primary metabolism is controlled by these enzymes. PMID- 1611804 TI - Dextromethorphan: enhancing its systemic availability by way of low-dose quinidine-mediated inhibition of cytochrome P4502D6. AB - There has been a substantial amount of interest in the anticonvulsant and neuroprotective actions of dextromethorphan. Its therapeutic efficacy, however, is limited by its extensive first-pass elimination by way of the cytochrome P4502D6 enzyme in humans. The purpose of this research was to determine whether quinidine (a selective inhibitor of cytochrome P4502D6) could improve dextromethorphan systemic delivery in patients with amyotrophic lateral sclerosis (a neurodegenerative disease). In the absence of quinidine, 60 mg dextromethorphan every 12 hours resulted in plasma concentrations of only 12 +/- 13 ng/ml (range, less than 5 to 40 ng/ml; n = 7). The same dose of dextromethorphan in the presence of 75 mg quinidine every 12 hours resulted in dextromethorphan plasma concentrations of 241 +/- 94 ng/ml (range, 157 to 402 ng/ml; n = 5). The achievement of higher dextromethorphan plasma concentrations was also associated with an increased occurrence of adverse effects in some patients. Based on the brain/plasma ratio for dextromethorphan in rats, it is estimated that brain dextromethorphan concentrations of 1.0 to 10 micrograms/gm may be attainable in humans by inhibition of cytochrome P4502D6 activity with quinidine. PMID- 1611806 TI - Clinical pharmacokinetics of 3'-azido-3'-deoxythymidine (zidovudine) and catabolites with formation of a toxic catabolite, 3'-amino-3'-deoxythymidine. AB - This study investigated pharmacokinetics and metabolism of 3'-azido-3' deoxythymidine (zidovudine) in patients after a 1-hour intravenous infusion of 2.5 mg/kg zidovudine with a radiolabeled tracer amount of [5-3H]-zidovudine. In addition to unchanged drug and its 5'-O-glucuronide (zidovudine glucuronide), two novel catabolites of zidovudine were detected as 3'-amino-3'-deoxythymidine (AMT), and its 5'-O-glucuronide (GAMT). The AMT apparent plasma elimination half life (2.70 +/- 0.7 hours) was longer than that of zidovudine (1.20 +/- 0.30 hours) and zidovudine glucuronide (1.60 +/- 0.5 hours). The zidovudine/AMT plasma peak concentration and area under the concentration-time curve ratios were approximately 8 and 5, respectively. Urinary recovery of radioactivity was essentially complete within 24 hours. AMT glucuronide was not detected in urine or plasma, and only low levels of this catabolite were detected in bile. In contrast, AMT was not detected in bile. The substantial levels of AMT in the plasma of patients after zidovudine administration suggests that this catabolite may affect the pharmacodynamic properties of zidovudine in relation to its activity against human immunodeficiency virus replication and cytotoxicity to host cells. PMID- 1611807 TI - The disposition of dapsone in cirrhosis. AB - Acetylation and N-hydroxylation of dapsone were evaluated in drug-free, non smoking, normal subjects and subjects with cirrhosis (n = 7 for each group) after oral administration of 100 mg dapsone. Acetylation was not correlated with oral dapsone clearance or reduced in cirrhosis (0.37 +/- 0.43 versus 0.52 +/- 0.32). Fractional metabolic clearance of dapsone to its hydroxylamine was associated with dapsone oral clearance (r = 0.96, p less than 0.001, n = 14). In patients with cirrhosis, liver disease was associated with a trend to reduction in oral clearance (22%) and metabolic clearance of dapsone (48%). Protein binding was minimally reduced by cirrhosis (73% +/- 1% versus 69% +/- 3% in patients with cirrhosis (p less than 0.02). The dapsone recovery ratio was validated as a phenotypic index of the metabolic clearance of dapsone (r = 0.74, p less than 0.05). In an extended comparison of 14 patients with cirrhosis to 70 control subjects, cirrhosis was associated with reductions of 28% in dapsone recovery ratio (p less than 0.001), and 37% in acetylation ratio (p less than 0.01). Neither dapsone recovery ratio nor acetylation ratio correlated with Pugh Score, conventional liver function tests, indocyanine green clearance, or phenotypic measures of S-mephenytoin hydroxylase or debrisoquin hydroxylase activity. We conclude that cirrhosis is associated with minor changes in dapsone disposition and that dosage modification is not required. In addition, there is evidence that cirrhosis has a selective influence on activity of individual isozymes of cytochrome P450. PMID- 1611808 TI - The pharmacokinetics of high-dose carboplatin in pediatric patients with cancer. AB - Carboplatin disposition was studied in 18 pediatric patients with cancer over a dosage range of 400 to 700 mg/m2 given on an alternate-day schedule (total doses of 1200 to 2100 mg/m2) with high-dose etoposide. Median age was 7.7 years, hepatic functions were normal, and serum creatinine levels were less than or equal to 1.0 mg/dl. Carboplatin pharmacokinetics were determined by atomic absorption spectroscopy. Median pharmacokinetic parameters for ultrafilterable platinum were as follows: clearance 45.8 ml/min/m2 (range, 25.5 to 65.3 ml/min/m2) and a terminal half-life of 3.6 hours (range, 2.1 to 14.2 hours). Carboplatin clearance (CL) values and volume of distribution (VC) were highly correlated to body size (CL = 55 x Body surface area in [BSA, in square meters] - 6.7, r2 = 0.73; VC = 5 x BSA [in square meters] + 0.26, r2 = 0.69). However, carboplatin doses normalized to BSA still resulted in twofold to threefold variability in area under the concentration-time curve. Carboplatin CL was significantly lower in those subjects (n = 9) who had previously received cumulative cisplatin doses of greater than or equal to 960 mg/m2 (p less than 0.05) but was not influenced by age, gender, or diagnosis. PMID- 1611809 TI - An additive or synergistic drug interaction: application of concentration-effect modeling. AB - Although a conventional pharmacokinetic analysis can identify the pharmacokinetic component in a drug interaction, the pharmacodynamic component is less accessible and, ideally, should be evaluated over a range of doses. The potential of integrated concentration-effect modeling to avoid such multiple-dose studies has been evaluated in this study of the hypotensive effect of the combination of prazosin and verapamil, which has previously been shown to be more than simply additive. Characterization of the blood pressure responses (by concentration effect modeling) revealed that for supine diastolic blood pressure, responsiveness was significantly higher at 3.3 +/- 0.5 mm Hg per ng/ml when prazosin was combined with verapamil (p less than 0.01) compared with 2.4 +/- 0.5 and 2.4 +/- 0.4 mm Hg per ng/ml, respectively, for standard doses and augmented doses of prazosin alone. These findings suggest that there are both pharmacokinetic and pharmacodynamic components in the interaction between prazosin and verapamil and illustrate the applicability of concentration-effect modeling for investigating drug interactions. PMID- 1611811 TI - Caring about health care. PMID- 1611810 TI - Pharmacokinetic-pharmacodynamic modeling of the central nervous system effects of midazolam and its main metabolite alpha-hydroxymidazolam in healthy volunteers. AB - The pharmacodynamics of midazolam and its main metabolite alpha-hydroxymidazolam were characterized in individual subjects by use of saccadic eye movement and electroencephalographic (EEG) effect measurements. Eight healthy volunteers received 0.1 mg/kg midazolam intravenously in 15 minutes, 0.15 mg/kg alpha hydroxymidazolam intravenously in 15 minutes, 7.5 mg midazolam orally and placebo in a randomized, double-blind, four-way crossover experiment. Plasma concentrations of midazolam, alpha-hydroxymidazolam and 4-hydroxymidazolam were measured by gas chromatography. The amplitudes in the 11.5 to 30 Hz (beta) frequency band were used as EEG effect measure. The concentration-effect relationships were quantified by the sigmoid maximum effect model. The median effective concentrations of midazolam and alpha-hydroxymidazolam were (mean +/- SE) 77 +/- 15 and 98 +/- 17 ng/ml, respectively, for the EEG effect measure. For peak saccadic velocity the values were 40 +/- 7 ng/ml for midazolam and 49 +/- 10 ng/ml for alpha-hydroxymidazolam. The maximum effect values were similar for both compounds. The effects observed after oral administration of midazolam could not be predicted accurately by an additive and competitive interaction model. It seems that alpha-hydroxymidazolam is highly potent with respect to the measured effects and contributes significantly to those effects of midazolam after oral administration. PMID- 1611812 TI - Gram-negative sepsis, the sepsis syndrome, and the role of antiendotoxin monoclonal antibodies. AB - The incidence and mortality, pathogenesis, clinical manifestations, and management of sepsis and the sepsis syndrome are reviewed, and the use of antiendotoxin monoclonal antibodies to treat patients with sepsis is discussed. The sepsis syndrome and septic shock are induced by the presence of endotoxin, a lipopolysaccharide found in the outer membrane of gram-negative bacteria. Proper management of gram-negative sepsis includes appropriate antimicrobial therapy, fluids and electrolytes, nutritional support, administration of vasopressors, and mechanical ventilation if necessary. To date, two antiendotoxin monoclonal antibodies have been produced and subjected to extensive clinical testing. HA-1A, a human cell line-derived monoclonal immunoglobulin M (IgM) antibody that contains only a small fragment of murine protein, was tested in one trial. HA-1A significantly reduced mortality in patients with sepsis and gram-negative bacteremia and produced better resolution of major morbidities than placebo in those patients. E5, an IgM antibody produced entirely via murine monoclonal antibody technology, was evaluated in two trials. Results from the first trial showed that E5 significantly reduced mortality in patients with gram-negative infection who were not in refractory shock. In contrast, results from the second trial did not show any significant reduction in mortality among patients with gram-negative infection who received E5. However, resolution of major morbidities occurred more frequently among E5 recipients in both trials. HA-1A and E5 were both well tolerated in the trials. The cost of therapy is expected to be $3000 $4000 per treatment course. The antiendotoxin monoclonal antibodies represent the next step along the path toward important reductions in morbidity and mortality from gram-negative infection. However, the financial implications of the use of HA-1A and E5 are enormous, and stringent patient selection criteria for administration of these products will have to be developed. PMID- 1611813 TI - Treatment of preeclampsia and eclampsia. AB - The characteristics and treatment of preeclampsia and eclampsia are reviewed. Risk factors for preeclampsia include (1) nulliparity, (2) a mother or sister(s) with a history of the disorder, (3) essential hypertension or renal disease, or (4) a twin or molar pregnancy. Preeclampsia is diagnosed when the systolic blood pressure (BP) increases by 30 mm Hg or the diastolic BP increases by 15 mm Hg after the 20th week of gestation and the BP rise is accompanied by edema, proteinuria, or both. Severe preeclampsia is diagnosed when the BP reaches or exceeds 160 mm Hg systolic or 110 mm Hg diastolic after bed rest. Eclampsia is the occurrence of seizures (in the preeclamptic patient) that cannot be attributed to other causes; it occurs in about 0.2% of preeclamptic patients. Magnesium sulfate (in the injectable, hydrated form) is the agent used most often for seizure prophylaxis in the preeclamptic patient in the United States. It is also used widely to control seizures once they develop. In the United States, diazepam is used to supplement magnesium sulfate if necessary to control seizures, but its use is not routine. Among antihypertensive agents, i.v. hydralazine is preferred in this country to control blood pressure in the severely preeclamptic or eclamptic patient. Several studies provide promising evidence that low-dose aspirin (60-150 mg daily beginning at 28-30 weeks of gestation) prevents preeclampsia in women who are at risk for its development. Until additional comparative studies are completed, magnesium sulfate and hydralazine will remain the standard of care for the treatment of preeclampsia in the United States. PMID- 1611814 TI - Systemic absorption of intraperitoneal antimicrobials in continuous ambulatory peritoneal dialysis. AB - The factors that influence drug movement across the peritoneum are presented, and the feasibility of administering antimicrobials intraperitoneally to treat systemic infections in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is explored. Antimicrobials are often administered intraperitoneally to treat peritonitis in patients undergoing CAPD. It would be advantageous to administer antimicrobials by the same route to treat systemic infections as well. Factors that determine the propensity of a drug to cross the peritoneal membrane include molecular weight, protein binding, volume of distribution, ionic charge, water or lipid solubility, the permeability and surface area of the peritoneum, blood flow rate, dialysate dwell time, and the concentration of dextrose in the dialysate. The bioavailability of i.p. drugs has been determined (1) by measuring the area under the plasma concentration-time curve (AUC) of an i.p. dose and comparing it with the AUC of the same dose given i.v. and (2) by estimating the residual drug content in the dialysate after a specified dwell period. Pharmacokinetic studies show that the bioavailabilities of antimicrobials given intraperitoneally in patients undergoing CAPD range from 50% to 92%. Vancomycin has been the agent most widely studied. Serum antimicrobial concentrations achieved by this route of administration are in many cases similar to those accomplished by the i.v. route and within the therapeutic range. Dosage regimens based on the pharmacokinetic data have been suggested; however, their efficacy has not been formally documented. The intraperitoneal route may have a role in the treatment of systemic infections in peritoneal dialysis patients, but specific recommendations cannot be made until clinical studies have been performed. PMID- 1611816 TI - Criteria for use of antiendotoxin monoclonal antibodies (HA-1A and E5) in adult and pediatric inpatients. PMID- 1611815 TI - Who should receive antiendotoxin monoclonal antibody therapy? PMID- 1611817 TI - Cellular proliferation markers in the evaluation of human cancer. AB - Our knowledge of normal growth regulatory mechanisms, and of the disordered growth that occurs during tumorigenesis, has greatly increased during the past decade. In particular, these studies have emphasized the importance of chromosomal alterations, genetic heterogeneity, and cell proliferation in tumorigenesis and metastasis. As a result, the early diagnosis and treatment of malignancy appear to be even more important than previously recognized. Clinical studies of tumor proliferative activity were first conducted by thymidine labeling techniques and more recently by flow cytometric analysis of DNA content. This information appears to provide important information that directly relates to tumor behavior and is of great prognostic significance in many tumors. In contrast, total nuclear DNA content, as measured by flow cytometry or image analysis, appears to be an "epi-phenomenon," and its clinical significance varies in different tumors. The potential clinical value of this research is enormous, because a rapid, accurate nonradioisotopic flow cytometric determination of tumor kinetic parameters, simultaneously with DNA content and surface antigen expression, would provide information of great importance for determining patient prognosis and making therapeutic decisions. Under these circumstances, analysis of DNA content and proliferative activity should be applied cautiously to patient care. Stringent quality control should be exercised, and the potential significance and limitations of these data should be clearly provided to the requesting physician. Most importantly, additional research during the next few years will provide answers to the many questions that remain about the appropriate clinical role of this information. As Stanbridge and Nowell stated at the conclusion of a recent Cold Spring Harbor meeting on the Origins of Human Cancer, "We have come a long way. . . and we have a very long way to go." PMID- 1611818 TI - Monoclonal antibodies in cancer immunotherapy. AB - The preceding article focused on some novel approaches for the adjuvant treatment of human melanoma and neuroblastoma with mAbs against antigens preferentially expressed on these tumors. It should be emphasized that the major goal of the immunotherapy modalities described here is to apply them in an adjuvant setting for the treatment of micrometastases. The major aim is to decrease the rate of development of metastases in a setting of very low tumor burden and ultimately achieve a prolongation in life span. The combination of powerful modern technologies achieving genetic engineering of mAbs, resulting in more human-like molecules, will lead to a reevaluation of these reagents alone or in combination with molecularly defined cytokines and growth factors for the immunotherapy of cancer. The initial, albeit anectodal, findings, of phase I clinical trials mentioned in this article lead to cautious optimism that immunotherapy may find a place and will eventually contribute to the adjuvant treatment of cancer. PMID- 1611819 TI - Structural and biologic properties of integrin-mediated cell adhesion. AB - The integrins are a family of proteins that mediate cellular adhesion mechanisms involved in development, differentiation, wound healing, immune recognition, and inflammation. In addition, these adhesion receptors also potentiate disease states including cancer, thrombosis, and inflammatory diseases. To understand the role of integrins in these processes, it is important to define their structural and functional properties. It is also imperative to understand the distribution of integrins on normal and malignant cell types. Integrins are regulated on the cell surface, and these events likely promote specific cellular adhesion mechanisms. This is of particular concern among tumor cells, which not only attach to the extracellular matrix but must invade and migrate through it. Integrins are surface-expressed proteins that mediate a linkage to the cytoskeleton within the cell, and thus cell morphology and traction during migration. Thus, by understanding the structural basis of integrin--ligand and integrin--cytoskeleton interactions we will gain insight into the molecular basis of cancer, thrombosis, wound healing, and inflammation. PMID- 1611820 TI - New developments in flow cytometric analyses of lymphocyte markers. AB - This article addresses several fundamental features of clinical flow cytometry. A practical overview of the technical and methodologic aspects of this fast-growing and increasingly important new clinical and investigative field is provided. The use of flow cytometry for the diagnosis and monitoring of various chronic lymphoproliferative diseases also is discussed. This article may serve as a useful guide to those seeking to set up or maintain a clinical flow cytometry laboratory. PMID- 1611821 TI - Chronic granulomatous disease: diagnosis and classification at the molecular level. AB - Chronic granulomatous disease (CGD) is caused by the failure of phagocytes to produce microbicidal derivatives of molecular oxygen, such as hydrogen peroxide. It is one of the best characterized of the phagocyte disorders and represents an important consideration in the differential diagnosis of recurrent infections. The clinical, biochemical, and molecular genetic aspects of CGD are reviewed in this context in this article. PMID- 1611822 TI - Review of testing for human immunodeficiency virus. AB - The performance of HIV testing requires meticulous attention to preanalytic, analytic, and postanalytic variables, especially matters of patient confidentiality. Laboratory directors must pay strict attention to quality control and quality assurance practices. Careful attention to these considerations can produce a screening program in low-prevalence populations that has an extremely low false-positive rate, with a positive predictive value of greater than 99%. Issuing a clear and concise laboratory report to the clinician is important. The Fifth Consensus Conference on Testing for Human Retroviruses of the Association of State and Territorial Public Health Laboratory Directors, March 1990, has recommended that ELISA be reported as reactive or nonreactive; IFA as reactive, nonreactive, or nonspecific, and WB as reactive, nonreactive, or indeterminate. It is recommended that the terms positive and negative be reserved for the summary interpretation given at the conclusion of the HIV-1 antibody testing algorithm. The testing algorithm used for HIV antibody screening at Scripps Clinic is shown in Figure 3. Other algorithms for complete testing on a single sample only or on two separate samples are reported. We agree with others that the patient should not be counseled for infection with HIV until a reactive confirmatory test(s) establishes a positive diagnosis. Certain special situations in diagnostic testing deserve comment. Establishing the diagnosis of HIV infection can be difficult in seronegative persons with acute infection. Polymerase chain reaction, viral culture or antigen detection may be useful tests in this situation. However, careful interpretation of test results and close correlation with patient risk factors are important to establish the proper diagnosis. Reports of seronegative persons, some remaining seronegative over a protracted time, have raised concerns over the transfusional risk of HIV infection. Blood donor screening programs are using careful donor qualification and recruitment practices that, combined with antibody testing, are highly effective in minimizing the risk of transfusion-transmitted HIV infection. A recent study reported the odds of contracting HIV infection from transfusion as 1:153,000 per unit transfused. Current screening strategies have been estimated to allow 20.5 infected units per million donated units to be transfused in high prevalence areas and 4.7 infected units per million donated units in low prevalence areas. As these studies indicate, there is a very small but identifiable risk of HIV infection in recipients of blood or blood products screened negative by current practices. The laboratory director must be versed in the comprehensive recommendations related to prevention of HIV transmission by blood and blood products.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611823 TI - The workload recording method. A laboratory management tool. AB - To provide the physician with an accurate, timely, and useful test result remains the primary goal of the laboratory. This article reviews the workload recording method developed by the College of American Pathologists to monitor the efficiency of personnel in the laboratory. Topics discussed include historical background, time studies, implementation and data collection, productivity ratios, and management applications. PMID- 1611825 TI - 'Glycosuria: please advise'. Reflections on undergraduate medical education. PMID- 1611824 TI - Methods to evaluate and develop the decision process in the selection of tests. AB - An objective, comprehensive method is described for organizing medical information that determines the most useful and sufficient test sets for separating diseases. The system is purposive, i.e., both its means and ends are known and tests results can be correlated with patient outcomes. The method is based on levels of information, probability and uncertainty and on measurement of comprehension and effectiveness. As the number of diseases in the system increases, the probability of their message sources decreases, which results in an increase in uncertainty. Resolution of uncertainty results in the diagnosis. Methods of reducing computational time are presented in this article. PMID- 1611826 TI - Oral disorders associated with diabetes mellitus. AB - The protean manifestations of diabetes include various associated oral disorders such as sialosis, xerostomia, impairment of taste, and localized infections of which oral candidosis is the most commonly observed. The association of specific oral diseases and diabetes is of importance both in the detection of undiagnosed diabetes and in the elucidation of the pathogenesis of various oro-facial diseases. The clinical features and possible causes of oral disorders recognized to be associated with diabetes are reviewed with emphasis on good oral hygiene in the diabetic patient. PMID- 1611827 TI - Recent trends in diabetes mortality in England and Wales. AB - Trends in diabetes-related mortality in England and Wales between 1975-6 and 1985 6, and regional and ethnic differences in diabetes-related mortality in 1985-6, have been examined. Data from death certificates mentioning diabetes in 1975-6 were compared with those for 1985-6 for different age groups. Data for 1985-6 were also analysed for different regions of England and Wales, and for country of birth. Between 1975-6 and 1985-6, the age-standardized rate of mentioning diabetes rose by 2.7% (95% confidence interval 1.4%, 4.1%) in men of all ages, and fell by 11.7% (10.6, 12.8) in women of all ages. By contrast, the rate of mentioning diabetes in those below 45 years fell by 30.7% (23.0, 37.7) in men and by 26.7% (16.5, 35.6) in women. Deaths in which the underlying cause was ischaemic heart disease (IHD), and where diabetes was also mentioned on the death certificate, rose by 14.4% (11.5, 16.8) in men and did not change significantly in women of all ages, but fell by 18.4% (-35.1, +2.6) in men, and 23.5% (-49.1, +15.2) in women below age 45. This was less favourable than the trend in the general population, where IHD mortality fell by 9.7% in men and 8.3% in women of all ages, and by 31.1% (28.6, 33.5) in men and 40.5% (35.0, 45.5) in women under 45 years.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611828 TI - Mortality of all incident cases of diabetes mellitus in Sweden diagnosed 1983 1987 at age 15-34 years. Diabetes Incidence Study in Sweden (DISS) Group. AB - From 1983 all incident cases of diabetes in the age group 15-34 years in Sweden have been recorded prospectively. The aim of the present study was to assess the mortality pattern of cases reported for 1983-87 and followed until the end of 1987. Eighteen deaths were identified by linkage to the national death register. When comparing the mortality in the cohort with Swedish males and females in general, an excess mortality was found in all the groups studied. It is, however, less pronounced if the analysis is restricted to those with Type 1 diabetes (standardized mortality ratio (SMR) and 95% confidence interval = 2.1; 0.8, 4.6), Type 2 diabetes (SMR = 4.8; 1.3, 12.3) or Type 1 + Type 2 (SMR = 2.7; 1.3, 5.0). Eight (44%) of the deaths were in patients with secondary diabetes, a diagnosis that applied to less than 3% of the cohort. Alcohol abuse was prevalent in six cases and suspected in another two. Hypoglycaemia was established as a cause of death in only one case but could not be excluded in a further six. Only one death was associated with ketoacidosis. No valid support for an increased risk of the 'dead in bed' syndrome was found. We suggest that diabetes was decisively important for the death in two cases and less important in 10. In the remaining six cases the existing documentation precludes a proper judgement. PMID- 1611829 TI - Prevalence of diabetes in different regional and religious south Asian communities in Coventry. AB - The prevalence of Type 2 (non-insulin-dependent) diabetes in different South Asian (Asian) communities was compared during the Coventry Diabetes Study, a cross-sectional house to house screening programme for diabetes. Screening was by capillary whole blood glucose measurement with oral glucose tolerance tests when concentrations were greater than or equal to 6.0 mmol l-1 within 2 h of a meal or greater than or equal to 5.0 mmol l-1 2 h or more after a meal and a random 10% of others. Of the 4395 resident Asians, 94% were represented by five communities: Punjabi Sikhs, Punjabi Hindus, Gujerati Moslems, Gujerati Hindus, and Pakistani Moslems. Response to screening was 77-89% and to glucose tolerance test was 59 79%. Differences in anthropometry, socioeconomic circumstances, and migratory patterns were found, but all groups had a higher prevalence of Type 2 diabetes than Europeans. Gujerati Moslems had the highest age-adjusted prevalence (per 1000) of Type 2 diabetes (males: 160 (95% CI 107-228), females: 204 (95% CI 144 283)) when compared with the other Asian groups (males: Punjabi Sikhs 89(72-110), Pakistani Moslems 91(67-120), Gujerati Hindus 84(57-120), Punjabi Hindu 113(74 171); females: Punjabi Sikhs 75(60-94), Pakistani Moslems 103(78-133), Gujerati Hindus 88(62-122), Punjabi Hindu 116(77-174)). That all the Asian groups had a high prevalence of diabetes, in spite of their known dietary, cultural, and socioeconomic differences, suggests that the Asian predisposition to Type 2 diabetes is inherited although environmental factors may be necessary for this to be expressed. PMID- 1611830 TI - The short insulin tolerance test for determination of insulin sensitivity: a comparison with the euglycaemic clamp. AB - The glucose clamp technique is currently regarded as the standard test for measuring insulin sensitivity against which other methods are compared but is unsuitable for routine screening of patients outside a hospital base. There is thus a need for a simpler test to measure insulin sensitivity. We have therefore compared the glucose disappearance rate KITT in the first 15 min of the insulin tolerance test (ITT) with the M and M/I values derived from the standard euglycaemic clamp in nine normal subjects and eight subjects with Type 2 (non insulin dependent) diabetes mellitus and coexisting obesity. All subjects underwent the ITT and euglycaemic clamp in random order. Nine subjects later had a repeat ITT to determine the reproducibility of the test. In the ITT, 0.1 U kg-1 body weight, human Actrapid insulin was given as an IV bolus and simultaneous arterialized and venous blood samples were obtained every minute for 15 min. The first order rate constant for the disappearance of glucose KITT over the period 3 15 min was taken as a measure of insulin sensitivity. The euglycaemic clamp was performed with an insulin infusion of 50 mU kg-1 h-1 for 120 min and a variable rate glucose infusion to maintain blood glucose concentration at 0.5 mmol l-1 below fasting level to minimize the effect of endogenous insulin secretion. The ratio of the mean rate of glucose infused (M, mumol kg-1 min-1) to the plasma insulin over the last 30 min of the clamp was taken as a measure of tissue sensitivity to insulin (M/I) assuming endogenous glucose output was suppressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611831 TI - Sequential metabolic studies of pancreas allograft function in type 1 diabetic recipients. AB - We have previously shown that the loss of acute first phase insulin secretion precedes pancreas allograft rejection and development of glucose intolerance in Type 1 diabetic patients. In order to examine whether there is a progressive loss of phases of insulin secretion and beta-cell function in technically successful pancreas transplants during the first year, we measured glucose, insulin, and C peptide responses to physiological (mixed meal) and pharmacological (IV glucose and IV glucagon) stimulation in 27 glucose-tolerant, insulin-independent allograft recipients at 3, 6, and 12 months. Mean +/- SE fasting serum glucose levels were normalized throughout the study period. Postprandial serum glucose profiles tended to increase by 12 months compared to 3 and 6 months, although peak glucose levels were not statistically different. Following pancreas transplantation, basal serum insulin levels were high at 3 months (163 +/- 17 pM), 6 months (165 +/- 22 pM), and 12 months (248 +/- 54 pM, p = NS) in the Type 1 diabetic pancreas allograft recipients when compared to normal (25 +/- 3 pM). We observed slight elevations in postprandial insulin and C-peptide profiles at 12 months compared to 3 and 6 months. Following IV glucose and glucagon stimulation, serum insulin and C-peptide levels as well as phases of insulin release did not differ over the 12-month study period. Similarly, the glucose decay constant (KG) was nearly identical at 3, 6, and 12 months. In summary, 1 year following successful whole cadaveric, heterotopic pancreas transplantation in Type 1 diabetic recipients, fasting serum glucose remains normalized, while postprandial glucose tends to rise.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611832 TI - The use of low glycaemic index foods improves metabolic control of diabetic patients over five weeks. AB - The aim of the present study was to determine whether any benefit might occur from lowering the glycaemic index of diet in the medium term in diabetic patients. Eighteen well-controlled diabetic patients (12 Type 1 and 6 Type 2 non insulin-treated), were assigned to either a high mean glycaemic index or low mean glycaemic index diet for 5 weeks each in a random order using a cross-over design. The two diets were equivalent in terms of nutrient content and total and soluble fibre content. The glycaemic indices were 64 +/- 2 (mean +/- SD) % and 38 +/- 5% for the two diets. The high glycaemic index diet was enriched in bread and potato and the low glycaemic index diet in pasta, rice, and legumes. At the end of the study periods, the following variables were improved on the low compared to the high glycaemic index diet: fructosamine (3.9 +/- 0.9 vs 3.4 +/- 0.4 mmol l 1, p less than 0.05); fasting blood glucose (10.8 +/- 2.8 vs 9.6 +/- 2.7 mmol l 1, p less than 0.02); 2-h postprandial blood glucose (11.6 +/- 2.9 vs 10.3 +/- 2.5 mmol l-1, p less than 0.02); mean daily blood glucose (12.0 +/- 2.5 vs 10.4 +/- 2.7 mmol l-1, p less than 0.02); serum triglycerides (1.5 +/- 0.9 vs 1.2 +/- 0.6 mmol l-1, p less than 0.05). No significant differences were found in body weight, HbA1C, insulin binding to erythrocytes, insulin and drug requirements, and other circulating lipids (cholesterol, HDL-cholesterol, phospholipids, Apolipoprotein A1, Apolipoprotein B). Thus the inclusion of low glycaemic index foods in the diet of diabetic patients may be an additional measure which slightly but favourably influences carbohydrate and lipid metabolism, requires only small changes in nutritional habits and has no known deleterious effects. PMID- 1611834 TI - Screening for diabetic retinopathy in a widely spaced population using non mydriatic fundus photography in a mobile unit. Tayside Mobile Eye Screening Unit. AB - A screening project was established to assess the prevalence and severity of retinopathy in diabetic patients in Tayside (area: 3000 square miles, population: 390,000). A questionnaire was used to examine patient acceptability. Of 2112 patients photographed during the first year, 32% had abnormal photographs; 20.2% had diabetic retinopathy; 7.4% cataracts; 4.6% non-diabetic eye disease. Among this patient population, 73% were registered at a hospital diabetic clinic. The overall prevalence of diabetic retinopathy was similar between the two groups (hospital 23% vs non-hospital 20%). The prevalence of severe diabetic retinopathy was also similar (hospital 8.5% vs non-hospital 10%). This had been previously unrecognized or incorrectly defined in 6.5% of those not attending a hospital diabetic clinic, compared to 3.7% attending the hospital clinic (p less than 0.01). A favourable response to the service was indicated by 40% of patients with 7% unfavourable and 41% uncommitted. Non-mydriatic fundal photography housed in a mobile unit is a practical and effective method of assessing diabetic retinopathy. It is particularly suitable for screening in a widely spread population. PMID- 1611833 TI - Beneficial effect of a low glycaemic index diet in type 2 diabetes. AB - Low glycaemic index foods produce low blood glucose and insulin responses in normal subjects, and improve blood glucose control in Type 1 and well-controlled Type 2 diabetic patients. We studied the effects of a low glycaemic index diet in 15 Type 2 diabetic patients with a mean fasting blood glucose of 9.5 mmol l-1 using a randomized, crossover design. Patients were given pre-weighed diets (59% energy as carbohydrate, 21% fat, and 24 g 1000-kcal-1 dietary fibre) for two 2 week periods, with a diet glycaemic index of 60 during one period and 87 during the other. On the low glycaemic index diet, the blood glucose response after a representative breakfast was 29% less than on the high glycaemic index diet (874 +/- 108 (+/- SE) vs 204 +/- 112 mmol min l-1; p less than 0.001), the percentage reduction being almost identical to the 28% difference predicted from the meal glycaemic index values. After the 2-week low glycaemic index diet, fasting serum fructosamine and cholesterol levels were significantly less than after the high glycaemic index diet (3.17 +/- 0.12 vs 3.28 +/- 0.16 mmol l-1, p less than 0.05, and 5.5 +/- 0.4 vs 5.9 +/- 0.5 mmol l-1, p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611835 TI - A 12-month randomized controlled study of the aldose reductase inhibitor ponalrestat in patients with chronic symptomatic diabetic neuropathy. AB - The effects of the aldose reductase inhibitor ponalrestat (600 mg day-1) on sensory, electrophysiological, and autonomic function were examined in 50 patients with chronic symptomatic, distal symmetrical diabetic neuropathy in a 52 week randomized, double-blind, parallel-group, placebo-controlled, single-centre study. In an endeavour to identify patients with a degree of neuropathy potentially amenable to pharmacological intervention, a minimum conduction velocity of 30 m s-1 was set for the peroneal motor nerve. At 52 weeks, no significant differences were observed between the ponalrestat and placebo groups in motor (ulnar, median, and peroneal) or sensory (ulnar and radial) nerve conduction velocities, vibration perception thresholds, adjectival symptom scores or tests of autonomic function (mean electrocardiographic R-R interval variability on deep breathing and orthostatic blood pressure response). Ponalrestat was clinically well tolerated and had no significant effect on glycaemic control. The lack of beneficial effects of ponalrestat may in part reflect the advanced stage of the neuropathic process in patients with established symptomatic disease, and the poor reproducibility of current neurophysiological techniques. Firmer knowledge of clinico-pathological correlates allied to improved non-invasive neurophysiological measurement techniques should facilitate the selection of patients for future therapeutic trials in diabetic neuropathy. PMID- 1611836 TI - Problems with gait and posture in neuropathic patients with insulin-dependent diabetes mellitus. AB - Peripheral neuropathy secondary to diabetes mellitus is believed to cause postural instability and uncoordinated gait, although this is not well documented. Two groups of patients from the Pittsburgh Epidemiology of Diabetes Complications Study, matched for age and duration of Type 1 diabetes, but with significantly different vibratory sensation thresholds as determined by Vibratron II testing, were therefore surveyed. The mean ages were 32.9 and 31.9 years and durations of diabetes were 22.0 and 18.8 years for the neuropathic and control groups, respectively. Patients provided details of fall injuries, and perception of safety during standing and walking. Multiple linear and logistic regression models were used to account for potentially associated variables such as gender, retinopathy, and duration of diabetes. The neuropathic group had adjusted odds ratios for reported injuries during gait of 15.0 relative to the control group (95% confidence intervals 1.04-216.59). The neuropathic group also reported significantly lower scores (less safe, p = 0.004) than the control group on perceived safety in unusual conditions. It is concluded that peripheral neuropathy has an effect on gait and posture which is clinically significant and that this effect merits further biomechanical study in neuropathic patients. PMID- 1611837 TI - Diabetes education: whose priorities are met? AB - Two hundred Type 2 diabetic patients newly referred to the diabetes centre at a large university teaching hospital were studied over an 8-month period. Patients completed a diabetes knowledge questionnaire, and specified their educational priorities by selecting six diabetes-related topics from a list of 14. After giving 1 h of individual education and using the same list, the educators selected six topics which they considered to be most important for that particular patient to know. Choice of educational priorities differed between the patients and the corresponding educator (p less than 0.001). In only 38% of cases did the educators' first three priorities coincide with those of the patients. The major discrepancies were in the selection of 'sick day management' and 'complications', especially favoured by patients, as against 'oral hypoglycaemic agents' and other therapy-related topics, especially favoured by educators. Diabetes knowledge was a determinant of educational priority for patients (p less than 0.001) but not educators. In contrast, only the educators' overall choices were affected by duration of diabetes (p less than 0.001). Diabetes treatment type influenced both patients' and educators' selection of priorities (p less than 0.001). We conclude that an educational strategy which relies on health professionals' perceptions to determine what diabetic patients need to know may be inadequate. PMID- 1611838 TI - Hypoglycaemic, antihyperglycaemic and antidiabetic drugs. PMID- 1611839 TI - Diabetes mellitus in The Gambia, west Africa. AB - A register of diabetic patients attending the Royal Victoria Hospital, Banjul, The Gambia, was kept and data on hospital admissions recorded over a 1-year period. Two hundred and sixty-nine patients (110 men, 159 women) were registered of whom 66 (25%) were receiving insulin. Seventy-five patients (28%: 40 men, 35 women) were newly diagnosed. There were significant differences in age (p less than 0.001) and obesity (p less than 0.001) between men and women and between patients with different types of diabetes. There were 95 hospital admissions (5.2%) related to diabetes, as were a fifth of medical out-patient attendances. Ketoacidosis was the major cause of death while foot infections were more common (p less than 0.01) in women. Diabetes imposed a heavy burden on the health services of The Gambia, a small developing country in West Africa; more than 3.6% of the annual health budget was spent on the treatment of diabetic patients. PMID- 1611840 TI - Minimal models and the labelled IVGTT. PMID- 1611841 TI - Spring meeting of the Medical and Scientific Section of the British Diabetic Association. 26-27 March 1992. Abstracts. PMID- 1611842 TI - Genetic heterogeneity among nutritionally deficient streptococci. AB - The nutritionally deficient (variant) streptococci (NDS) share the auxotrophic characteristic of requiring pyridoxal or thiol group supplementation for growth. The deoxyribonucleic acid relatedness of these organisms among themselves is unknown. Improved speciation of NDS would lead to a better knowledge of their pathogenesis and possible insight into improved clinical management. Therefore, DNA-DNA hybridization and biotyping of 23 nutritionally deficient streptococci were performed. Biochemical testing using the API Rapid Strept Identification method revealed that the organisms in this study were characterized among three broad biotype groups. Only one strain was nontypeable. DNA-DNA hybridization among the nutritionally deficient streptococci that we compared revealed genetic heterogeneity. Only four (17%) of 23 isolates were highly homologous; all were of biotypes 2 and 3. Reference viridans streptococcal strains had minimal homology to the NDS strains. The data indicate that the NDS are genetically heterogeneous. PMID- 1611845 TI - Rapid, direct identification of Staphylococcus aureus and Streptococcus pneumoniae from blood cultures using commercial immunologic kits and modified conventional tests. AB - To develop safe and rapid methods for identification of Staphylococcus aureus and Streptococcus pneumoniae directly from positive blood culture bottles (BCB) (BACTEC, Johnston Laboratories), several commercial biochemical and immunological tests as well as modified conventional tests were evaluated. Preliminary studies demonstrated that both S. aureus and St. pneumoniae could be identified directly using only a small aliquot (100 microliters) of the blood culture broth obtained via vent without need for centrifugation or other separation steps. A simple tube coagulase exhibited 98% sensitivity and 100% specificity for 32 S. aureus isolates and 157 blood cultures positive for coagulase-negative staphylococci when read at 2 hr. All systems employed for direct identification of St. pneumoniae exhibited excellent sensitivity and specificity using aliquots from blood culture broths, but Pneumoslide (BBL Microbiology Systems, Cockeysville, MD) was easiest to perform and interpret. The results of this study show that S. aureus and St. pneumoniae can be identified directly from blood culture broth aliquots using rapid methods that eliminate the need for centrifugation or use of needles and syringes. PMID- 1611843 TI - The CLED agar option in urine culture routine. A prospective and comparative evaluation. AB - Current recommendations for routine urine culture are still inoculation of specimens in a combination of solid media, usually blood agar (BA) plus MacConkey agar (MK). We have performed a prospective blind study comparing the accuracy of CLED agar (C), as the sole medium, with classic procedure (BA+MK). We included 1157 urine samples plated on the three culture media simultaneously. After incubation for 20-22 hr at 37 degrees C, the cultures were read by two of the authors independently. The cultures were evaluated according to standard criteria (BA+MK) considering a count above 10(4) CFU/ml as significant. The numbers of positive, negative, and contaminated cultures were 233, 764, and 160, respectively. Sensitivity and specificity of CLED were 98% and 99%, respectively. Fastidious microorganisms were accurately detected on C agar as well as on BA+MK. Morphologic differentiation of colonies was easier with C agar, and time required for inoculating and reading the plates was logically less in the C group. As the productivity of C is similar to that of standard procedures, its economy and convenience make it a medium worth using for routine culture of urine samples. PMID- 1611844 TI - Use of a commercial double-test tablet (Rosco PGUA/indole) for screening of Escherichia coli. AB - A commercial double-test tablet (Rosco PGUA/indole) for detection of beta glucuronidase (beta-GUR) activity and indole production was evaluated on a collection of 393 isolates of Enterobacteria. Both beta-GUR and indole were positive on 96.6% of Escherichia coli strains. beta-GUR, only, was also detected in 25 Shigella spp., four Enterobacter cloacae, eight Citrobacter freundii, and five Salmonella enteritidis strains, none of which were indole producers. An additional 261 consecutive clinical isolates of oxidase-negative nonswarming Gram negative bacilli were studied in a parallel comparative field trial against conventional identification methods. For 200 strains, the standard method and PGUA/indole test were performed from the primary culture plate. The remaining 61 (23.4%) required subculture before testing. Sensitivity, specificity, positive predictive value, and negative predictive value of PGUA/indole test in the screening for E. coli were, respectively, 94.1%, 100%, 100%, and 87.1%. In our experience, PGUA/indole test is a rapid, precise, simple-to-perform, and economical method for screening E. coli. However, the need for a large inoculum may limit its application on primary cultures. PMID- 1611846 TI - Evaluation of the pediatric Septi-Chek blood culture system. AB - The pediatric Septi-Chek blood culture system is a biphasic system that uses a 20 ml bottle of brain-heart infusion broth. We compared this system with a supplemented peptone broth tube (Vacutainer) for the recovery of aerobic organisms from blood cultures obtained from patients in a pediatric hospital. Blood specimens for culture were drawn into transport tubes containing sodium polyanetholsulfonate (SPS), and equal volumes were allocated into a Septi-Chek bottle and a Vacutainer tube which was vented for the first day of incubation. A total of 4828 blood culture sets was included, from which 243 probable pathogens were recovered, including 211 in the Septi-Chek system and 204 from the Vacutainer Tube. There were no significant differences in the recovery of individual pathogens. The mean time to initial detection of pathogens was comparable in the two systems, but the mean time to growth on solid media for pathogens recovered in both systems was shorter with Septi-Chek (37.2 hr compared with 45.5 hr, p less than 0.001). The pediatric Septi-Chek system is comparable with a vented Vacutainer tube for the recovery of aerobic pathogens, and its use facilitates the early identification and susceptibility testing of bloodstream pathogens. PMID- 1611847 TI - Inhibitory and bactericidal activity of selected beta-lactam agents alone and in combination with beta-lactamase inhibitors compared with that of cefoxitin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates of the Bacteroides fragilis group. AB - The inhibitory activity of five beta-lactam agents, alone and in combination with a beta-lactamase inhibitor, was compared with that of cefoxitin and metronidazole against 300 beta-lactamase producing Bacteroides fragilis group isolates. Each of the beta-lactamase inhibitors significantly potentiated the activity of the respective beta-lactam. In the presence of clavulanate, the MIC90 (minimum inhibitory concentration) values of amoxicillin and ticarcillin were reduced 64 fold and 32-fold, respectively. Similarly, sulbactam enhanced the activity of ampicillin and cefoperazone 16-fold and 8-fold, respectively, whereas tazobactam potentiated the activity of piperacillin 16-fold. Few strains were resistant to the beta-lactam-beta-lactamase inhibitor combinations and were comprised of strains of B. fragilis, B. thetaiotamicron, and B. distasonis. Of the strains, 7% were resistant to cefoxitin, and none to metronidazole. Using time-kill kinetic studies, the bactericidal activity of the various beta-lactam agents, with and without beta-lactamase inhibitors, was determined and compared with that of cefoxitin and metronidazole against cefoxitin-susceptible and cefoxitin-resistant isolates of the B. fragilis group. Overall, metronidazole was the most bactericidal agent with all isolates being killed with less than or equal to 4 micrograms/ml at 24 hr. Ampicillin-sulbactam was the next most bactericidal agent with all isolates being killed with less than or equal to 16/8 micrograms/ml of ampicillin-sulbactam at 24 hr. Amoxicillin-clavulanate and cefoperazone-sulbactam had bactericidal activity similar to that of ampicillin-sulbactam. Piperacillin tazobactam and ticarcillin-clavulanate were bactericidal at higher concentrations with all isolates killed with 64 micrograms/ml of piperacillin and 128 micrograms/ml of ticarcillin combined with their respective beta-lactamase inhibitors. None of the beta-lactam agents alone was able to kill more than 19 of the 26 isolates. We conclude that beta-lactam agents combined with beta-lactamase inhibitors have both inhibitory and bactericidal activity against cefoxitin resistant members of the B. fragilis group provided that the concentrations achieved for these combinations are at the upper limits for maximum recommended dosing. Although isolates of the B. fragilis group have been reported to produce unusual beta-lactamases that are refractory to beta-lactamase inhibitors, none of the cefoxitin-resistant isolates tested in this study were resistant to the beta lactam-beta-lactamase inhibitor combinations. PMID- 1611848 TI - In vitro activity of cefquinome, a new cephalosporin, compared with other cephalosporin antibiotics. AB - The in vitro activity of cefquinome, a new aminothiazolyl cephalosporin with a C 3 bicyclic pyridinium group, was compared with ceftazidime, cefpirome, and cefepime. Cefquinome inhibited members of the Enterobacteriaceae at less than or equal to 0.5 microgram/ml for Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Citrobacter diversus, Salmonella Shigella, Proteus mirabilis, Morganella, and Providencia. Although most Citrobacter freundii and Enterobacter cloacae were inhibited by less than 2 micrograms/ml, some strains resistant to ceftazidime were resistant, [minimum inhibitory concentration (MIC) greater than 16 micrograms/ml]. Serratia marcescens were inhibited by less than 1 microgram/ml and Pseudomonas aeruginosa by 8 micrograms/ml similar to the activity of cefepime. The majority of Haemophilus influenzae and Neisseria gonorrhoeae were inhibited by less than 0.25 microgram/ml. Most enterococci had cefquinome MICs of 4-8 micrograms/ml. Cefquinome was extremely active against group-A streptococci and Streptococcus pneumoniae with MICs less than 0.12 microgram/ml. 90% of methicillin-susceptible Staphylococcus aureus 90% were inhibited by 2 micrograms/ml. Overall, the in vitro activity of cefquinome was comparable with aminothiazolyl cephalosporins. It inhibited some Enterobacter and Citrobacter freundii resistant to ceftazidime as did cefpirome and cefepime. Cefquinome was not destroyed by the common plasmid beta-lactamases TEM-1, TEM-2, SHV-1, or by the chromosomal beta-lactamases of Klebsiella, Branhamella, and Pseudomonas, but it was hydrolyzed by TEM-3, TEM-5, and TEM-9. Its activity was not adversely decreased in different medium or protein, and minimum bactericidal concentrations (MBCs) for most species except for Enterobacter were within a dilution of MICs. PMID- 1611849 TI - Acute lymphatic filariasis in an American traveler. AB - Acute lymphatic filariasis developed in an American traveling recreationally to Asia. The illness was characterized by fatigue, eosinophilia, and lymphedema of the arm and chest wall, but no lymphangitis, lymphadenitis, or pain. Complete resolution occurred over 1-2 years. We discuss this syndrome and describe the use of new diagnostic tests in its diagnosis and management. PMID- 1611850 TI - Human infections with Actinomyces pyogenes (Corynebacterium pyogenes). AB - Actinomyces pyogenes (Corynebacterium pyogenes), a well-known pathogen in many animals, was isolated from 11 Danish patients since 1968. Bacteriologic characteristics and clinical pictures of the patients are described. Ability to hydrolyze gelatine, to produce beta-glucuronidase, to reach with antisera against group-G streptococci, and to produce acid from xylose differentiates A. pyogenes from Arcanobacterium haemolyticum, with which it has at times been confused. Actinomyces pyogenes is an established, but often misrecognized, human pathogen that should be better known to clinical microbiologists. PMID- 1611851 TI - Comparison of Buffalo green monkey kidney cells and McCoy cells for the isolation of Chlamydia trachomatis in shell vial centrifugation culture. AB - A total of 745 clinical specimens from patients attending hospitals and clinics in an area with a low prevalence of Chlamydia trachomatis were inoculated in parallel into shell vial cultures containing Buffalo green monkey kidney (BGM) and McCoy cells. The shell vial cultures were prepared in-house and were less than 5 days after seeding when inoculated. A total of 38 specimens (5%) were positive for C. trachomatis. In 36 of the cases, C. trachomatis was detected in both the BGM and McCoy vials. In two cases, C. trachomatis was detected in only the BGM vial. The BGM cells were more resistant to cytotoxicity and seemed to show more and larger inclusions than the McCoy cells. Furthermore, because the BGM cells displayed contact inhibition without the rounding and piling of cells that was encountered with the McCoy cells, they could be stored, ready to use, with an optical monolayer of cells, at 35 degrees C for at least 10 days. PMID- 1611852 TI - Fluorescent antibody staining test for rapid diagnosis of Shigella dysenteriae 1 infection. AB - An indirect fluorescent antibody test for rapid detection of Shigella dysenteriae 1 in diarrheal stools was developed. A diagnosis could be made within 90 min of submission of specimens to the laboratory. On comparison with culture results, the test had a sensitivity of 92%, a specificity of 93%, and positive and negative predictive values of 94% and 92%, respectively. PMID- 1611853 TI - Comparison of hemagglutination and hemadsorption tests for influenza detection. AB - Hemagglutination (HA) testing of the supernatant of primary rhesus monkey kidney cell culture tubes inoculated with clinical specimens was compared with hemadsorption (HAd) of the same tube for identifying the presence of hemagglutinin activity due to influenza. A total of 476 respiratory specimens were screened for influenza by this method. The 127 influenza or parainfluenza positive cultures showed 100% concordance between the two tests. All negative cultures were both also negative by HA and HAd. In contrast to the HAd method, HA testing was performed with less tube manipulation, less hands-on time, and less potential for cell culture tube contamination. PMID- 1611854 TI - In vitro activity of beta-lactam drugs and sulbactam against Chlamydia trachomatis. AB - We tested the in vitro activity of ampicillin, ampicillin-sulbactam, cefoperazone, cefoperazone-sulbactam, and sulbactam against 18 recent clinical isolates of Chlamydia trachomatis and two ATCC strains. Ampicillin (MIC50, 256 micrograms/ml) and sulbactam (MIC50, 128 micrograms/ml) demonstrated some activity against C. trachomatis, but cefoperazone had little to no activity. At 2 3 dilutions below the MIC, C. trachomatis treated with ampicillin or sulbactam, but not cefoperazone, formed small inclusions that remained small on passage onto antibiotic-free McCoy cells. It appears that ampicillin and sulbactam suppress rather than kill C. trachomatis. PMID- 1611856 TI - The mental health HMO: capitation funding for the chronically mentally ill. Why an HMO? AB - Excesses associated with deinstitutionalization during the 1970s provided a legacy of homelessness, revolving door rehospitalization, and gridlock in metropolitan hospital emergency rooms. To allow for the seriously and persistently mentally ill to move planfully into community life, caregivers must utilize new and improved care models. One option is the HMO capitation model being tested in the Monroe/Livingston County Mental Health Demonstration in New York State. Experience indicates positive results for patients and lower than anticipated costs. Integrated Mental Health (IMH) is the local authority for this locally designed demonstration in New York State. Community Mental Health Centers (CMHCs) act as "Lead Agencies" to manage care and rehabilitation for seriously mentally ill patients previously dependent totally on the State hospitals' services. Both improvements in patient functioning and in reduced cost of appropriate community care are being documented by this demonstration project. PMID- 1611855 TI - The postantibiotic suppressive effect of L-ofloxacin, an optically active isomer of ofloxacin. AB - The postantibiotic suppressive effect (PAE) of L-ofloxacin was studied and compared with those of ciprofloxacin and norfloxacin. The PAE of L-ofloxacin was observed against all Gram-positive organisms tested: Staphylococcus aureus, S. epidermidis, and Enterococcus faecalis. At the achievable serum concentrations L ofloxacin showed a longer PAE than ciprofloxacin and norfloxacin. Exposure of organisms to 4 micrograms/ml of L-ofloxacin for 2 hr produced a 3.1 and 4.2 hr PAE for methicillin-sensitive and methicillin-resistant staphylococci, respectively. Against E. faecalis and S. epidermidis, the PAEs of L-ofloxacin were 1.9 and 1.6 hr, respectively. PMID- 1611857 TI - The cost of fragmented mental health financing: is it worth it? AB - Three major aspects of mental health systems--the way they are financed, the configuration of services, and the outcome of services--are discussed. Problems of resource consumption, fragmentation of goals, and deleterious impacts due to financing systems, per se, are described. Levels of staff involvement in the financing system (as distinct from direct services) influence staff attitudes toward financing, services, and clients. Financing schemes appear to both influence the effectiveness of mental health systems and provide the dubious "advantage" of costing more. Studies are suggested that will compare comprehensive systems with an eye toward reform. PMID- 1611858 TI - Rural mental health appointment adherence: implications for therapy. AB - Appointment adherence is a significant concern for community mental health centers. In this investigation adherence, cancellations and non-adherence in a rural county was assessed. Overall, 69.3% of the scheduled appointments were kept, 13.7% canceled, and 17% failed. There were no significant differences found between individuals and couples, females and males, or initial and ongoing contracts. Results are encouraging since they are similar to rates reported for other settings and populations. The present findings highlight the importance of the client-therapist relationship and suggest the need for brief therapy in rural communities. PMID- 1611859 TI - Adaptation: the key to community psychiatric practice in the rural setting. AB - Psychiatric practice in the rural community mental health center can be arduous and challenging. Faced with limited resources, the full-time psychiatrist practicing in this setting must learn to be innovative and creative in order to adequately address the needs of this special population. Additionally, the social problems of poverty, domestic violence, and the lack of formal education impact on psychiatric treatment in rural centers to a very large degree. Clinicians must carefully consider ways in which they can interface with existing institutions and other community caregivers in providing mental health services. This paper discusses one clinician's experience in providing psychiatric services to patients in rural Kentucky. PMID- 1611860 TI - Clinical encounters with outpatient coercion at the CMHC: questions of implementation and efficacy. AB - Clinical encounters with three outpatients at a CMHC who were managed with alternating periods of voluntary or uncoerced and involuntary or coerced treatment are presented. The two periods of coerced community treatment--of eight months and then two to four years duration--produced positive results quite distinct from the periods of uncoerced community treatment. In discussing the implementation and efficacy of coerced outpatient treatment at the CMHC, the author addresses legal, clinical, and resource issues which form the basis for seven arguments often heard as to why staffs at CMHCs hesitate to employ involuntary or coercive interventions. PMID- 1611862 TI - Families' perceptions of community mental health programs for their relatives with a severe mental illness. AB - Realization that families are providing a major portion of the care for people with a severe and persistent mental illness has led to attempts to form an alliance with such families. Many professionals are aware that there is much cognitive distance between families and the professional community. Bridging this gap requires knowledge of the subjective experience of families. This paper reports the results of a study of the families' perspective of their experience with community mental health programs. Attention is given to the families' experience and needs; to changes in practice which address those needs; and to a variety of curriculum strategies for more adequately preparing future cadres of mental health professionals. PMID- 1611861 TI - Toward the financial integration of public mental health services. AB - The public treatment of seriously mental ill patients continues to be frustrated by the lack of administrative and financial integration of state and community mental health services. Several states have initiated attempts to improve the cost-effectiveness of public mental health services through mechanisms that create financial incentives fostering community-based alternatives to psychiatric hospitalization. Examples of such mechanisms include capitation financing systems, performance contracts, regional mental health authorities, utilization review, and bed-targets. This paper reviews evidence supporting the need for and success of these efforts, and also addresses their limitations. PMID- 1611863 TI - Social networks of residents in supportive housing. AB - One goal of supportive housing is to enlarge and improve the functioning of the social support networks of residents. The networks of a convenience sample of 42 residents were assessed using scales developed by Barrera. The size of the networks (11.5) was no larger than that reported for similar clients living in other types of community settings but the composition differed. Staff and co residents appear to partially replace rather than add to family and friends. This is of concern because friends are uniquely important determinants of satisfaction. An association between perceived need for support and network size was also found. These findings suggest some positive influences but also raise questions about unintended negative consequences of living in artificially constructed social environments. PMID- 1611864 TI - Normal housing: a key element of a supported housing approach for people with psychiatric disabilities. AB - This article summarizes current thinking in the field about the types of housing environments which are most relevant both to the overall goal of community integration, and to the variety of specific support needs of individuals with psychiatric disabilities. Within the context of a "supported housing" approach, which focuses on maximizing consumers choices and preferences, using integrated regular housing stock, and making a full array of community supports available, the authors propose a number of specific criteria which can be useful to community mental health organizations in planning for, or selecting housing. PMID- 1611865 TI - A model for measuring the implementation of community support programs: results from three sites. AB - We present and test a model for measuring the implementation of Community Support Programs (CSPs) for persons with severe mental illnesses. The model is intended to facilitate the description and replication of these programs and the future study of their critical ingredients. The model defines important implementation variables in seven areas of program functioning; we then suggest instruments to measure each of these variables. Results of a study examining the application of the model and measures to three conceptually distinct CSPs illustrate the utility of the model and measures for implementation analysis of CSPs. Importantly, findings revealed that a priori hypotheses about how the programs were expected to differ on the implementation variables were largely supported. PMID- 1611866 TI - A collaborative model of a county crisis intervention team: the Lake County experience. AB - A model is introduced for the classification of crisis intervention and disaster services as being clinic-based, ad hoc, school-oriented, disaster service based and integrative. An example is presented of an integrative-collaborative model that was developed in Lake County, Ohio to cope with situations of suicide, accidental death or natural disaster when they occur in rural areas and small towns. The Community Crisis Intervention Team (CCIT) was developed with characteristics specific to a collaborative model. The distinctive qualities of the CCIT are identified and discussed within the context of a case study of a postvention in a school setting following adolescent suicide. PMID- 1611867 TI - Psychiatry in community mental health centers: everyone can win. AB - The purpose of this paper is to describe the psychiatrist's role in community mental health programs, beginning with the evolution of psychiatric involvement in community mental health centers (CMHCs). There is a discussion of the current state of psychiatry in community mental health programs with descriptions of the types of roles psychiatrists occupy and their thoughts about those roles. The concluding sections focus on the ways psychiatrists can be utilized in community mental health programs so that both the psychiatrist and the agency benefit and are satisfied. PMID- 1611868 TI - The biochemical phylogeny of guinea-pigs and gundis, and the paraphyly of the order rodentia. AB - 1. Molecular data indicate that caviomorphs (guinea-pig-like rodents) and myomorphs (rat-like rodents) are not monophyletic. 2. Rather, the evolutionary lineage leading to the guinea-pig may have branched off prior to the divergence among myomorphs, lagomorphs, primates, chiropterans, artiodactyls, and carnivores. 3. Thus, the guinea-pig lineage probably represents an ancient eutherian lineage, and should be conferred an independent ordinal status. 4. The gundis (Ctenodactylidae) also seem to have branched off before the divergence among myomorphs, primates, and artiodactyls, but after the divergence of the guinea-pig. 5. Therefore, the order Rodentia as defined at the present time is in all probability a paraphyletic group devoid of taxonomic validity. 6. Previous claims pertaining to large differences in the rate of molecular evolution between guinea-pigs and myomorphs may have been exaggerated in many cases as a result of the erroneous phylogenetic position attributed to the guinea-pig. 7. The average rate of amino acid replacement in the guinea-pig is comparable to that in the rat and the mouse. 8. Protein-coding genes of myomorphs and caviomorphs evole, on average, about two times faster than their counterparts in gundis and humans. PMID- 1611870 TI - Species-specific heterogeneity for molecular weight estimates of serum extracellular superoxide dismutase activities. AB - 1. Several apparent molecular weights (mol. wt) are reported for plasma or serum extracellular superoxide dismutase (EC SOD) activity. This study found species dependent heterogeneity for apparent mol. wt using gel filtration with Sephadex G 150. 2. EC SOD activity in rabbit and guinea-pig serum, measured by a modified pyrogallol assay, eluted just before ceruloplasmin activity, but rat and bovine serum activity eluted after ceruloplasmin (apparent mol. wt of 142,000 and 73,000, respectively). 3. The heterogeneity between rat and rabbit serum was not eliminated by substituting a cytochrome-c-based SOD assay for the pyrogallol method, by substituting lung extracts for serum, by analysing a mixture of rat and rabbit serums, nor by analysing hemolysed serum. The apparent mol. wt of bovine serum EC SOD activity was not duplicated by gel filtration analysis of a mixture of bovine cytosolic SOD and albumin. 4. In conclusion, species-specific variation in apparent mol. wt for serum EC SOD activity was demonstrated under several circumstances. PMID- 1611869 TI - Metabolic end-products in parasitic helminths and their intermediate hosts. AB - Oxidoreductases which control the metabolic end-products in helminth parasites and their intermediate hosts were reviewed, in a trial to elucidate the respiratory metabolism during host-parasite associations. Special attention was given to Schistosoma parasites and their molluscan hosts. PMID- 1611871 TI - Different profiles of induced cotton effects of human and bovine lactoferrin by cibacron blue F3GA binding. AB - 1. The properties of complex formation of lactoferrin with Cibacron Blue F3GA dye have been studied by circular dichroic spectral analyses. The Cotton effects were induced by the interaction of lactoferrin with the dye and occurred in the wavelength range from 300 to 450 nm. 2. The patterns of changes in circular dichroic spectra of lactoferrin induced by the dye were different in bovine and human lactoferrin. 3. Iron ions bound to lactoferrin affected the profiles of induced Cotton effects in human lactoferrin but not in bovine lactoferrin. 4. While the dye bound co-operatively to human apo-lactoferrin, such co operativeness was not observed in iron-saturated human lactoferrin. PMID- 1611872 TI - Seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel (Citellus citellus): the effect of cold. AB - 1. The activity of antioxidant defense enzymes (SOD, CAT, GSH-Px and GST) was analysed during the autumn and winter in the ground squirrel adapted to 30 degrees C and subsequently exposed to cold for 6 and 24 hr. 2. The liver CAT activity as well as the IBAT CAT and GSH-Px activities differed between animals adapted to 30 degrees C, studied in autumn, and those studied in winter. 3. MnSOD activity in the liver was increased in autumn but decreased in winter after 6 hr cold exposure reaching the control level 24 hr later. Cold exposure induced a decrease in CAT activity (except after 24 hr cold exposure in winter) and an increase in GSH-Px activity. Lower GST activity was found after 24 hr exposure to cold in winter. 4. The IBAT SOD activity decreased under the influence of cold during both seasons with a tendency to return to the control level only in winter. Cold exposure produced a decrease in GST in both seasons and CAT activity in autumn. GSH-Px activity was increased in winter only. 5. The results indicate a seasonal dependence of the activity of antioxidant defence enzymes in the ground squirrel. Seasonal influence was evidenced in animals exposed to cold as well. PMID- 1611873 TI - Glucose metabolism in proliferating epithelial cells from the rat colon. AB - 1. The effects of fasting and fasting followed by refeeding on the activities of the oxidative pentose pathway (OPP) and the tricarboxylic acid cycle (TCA) in isolated rat colonocytes were estimated by the rate of production of 14CO2 from [1-14C]glucose and [6-14C]glucose, respectively. 2. Refeeding after a fast induced a 2-3-fold increase in glucose flux through the OPP and TCA cycle and the degree of change was similar in colonocytes from the proximal and distal colon. 3. Butyrate at a concentration of 40 mM inhibited the OPP by 20-30% (P less than 0.05) but had no effect on the activity of the TCA cycle. Glutamine at a concentration of 2 mM decreased the glucose flux through both the OPP and the TCA cycle by 30-50% (P less than 0.05). 4. Production of 14CO2 from the oxidation of butyrate or glucose indicated that the former was 5-7 times more active in colonocytes from fasted rats. After refeeding, however, butyrate utilization was similar to fasting values in the proximal colon but significantly lower (P less than 0.05) in the distal colon. PMID- 1611874 TI - Reversed-phase ion-paired HPLC of purine nucleotides from skeletal muscle, heart and brain of the goldfish, Carassius auratus L.--I. Development of the analytical method. AB - 1. A reversed-phase ion-paired liquid chromatographic (HPLC) method was developed to measure AMP, ADP, ATP, IMP, NAD+ and NADP+ levels in white muscle, heart and brain of anoxic goldfish. 2. Mobile phase parameters of the HPLC method (concentrations of buffer, organic modifier and counter-ion, and pH) were varied to establish the optimal conditions for separation of the compounds of interest. 3. The analytical method was evaluated by calculating some relevant chromatographic parameters (reproducibility and linearity). 4. The HPLC method showed sufficient selectivity, high sensitivity and reproducibility, and excellent linearity. PMID- 1611875 TI - Reversed-phase ion-paired HPLC of purine nucleotides from skeletal muscle, heart and brain of the goldfish, Carassius auratus L.--II. Influence of environmental anoxia on metabolite levels. AB - 1. The type and the amounts of some (di)nucleotides in white skeletal muscle, heart and brain of anoxic goldfish were established with a reversed-phase ion paired HPLC method. 2. Significant changes in the levels of these metabolites, as compared to controls, were observed. The most consistent change is the increase of IMP and of IMP-load (IMP/ATP + ADP + AMP) in the three tissues during anoxia. 3. Adenylate energy charges are maintained at a high level in the anoxic white muscle and the anoxic heart. Comparison of these results with those from conventional enzymatic methods for the quantification of (di)nucleotides showed, except for IMP, no significant differences. PMID- 1611876 TI - Purification of the sex steroid-binding protein from common carp (Cyprinus carpio) plasma. AB - 1. Sex steroid-binding protein was purified from common carp plasma. 2. Testosterone- and estradiol-binding activity existed at the same fraction eluted from gel Sepharose CL-2B, DEAE-Sephacel, hydroxylapatite and HPLC. 3. The molecular weight of the sex steroid-binding protein was 194,000. 4. At 50% displacement the order in which the steroids displaced [3H]testosterone bound to the binding protein was as follows: androstenedione greater than estradiol-17 beta greater than 11-deoxy-17-hydroxycorticosterone greater than 17 alpha hydroxyprogesterone greater than progesterone greater than deoxycorticosterone greater than estrone greater than 11-ketotestosterone greater than 17 alpha, 20 beta-dihydroxy-4-pregnen-3-one greater than androstenedione greater than pregnenolone greater than cortisone greater than cortisol. PMID- 1611877 TI - Purification of a sperm motility stimulator from porcine follicular fluid. AB - 1. We purified a glycoprotein possessing a potent ability to stimulate porcine sperm motility, from porcine ovarian follicular fluid. 2. The protein, of molecular weight 52,000, has an N-terminal sequence similar to that of antithrombin III, indicating that it is identical to or highly homologous to antithrombin III. 3. Thus it is proposed that antithrombin III or its homologue is involved in the mammalian fertilization process. PMID- 1611878 TI - Immunological analysis of chemoattractive proteins from earthworm to garter snakes. AB - 1. Two sets of polyclonal antibodies to two highly purified prey-derived snake attractive proteins, a low molecular weight (3000) protein and a 20,000 mol. wt protein, were generated in rabbits. 2. They are immunospecific for their respective purified immunogens and do not cross-react with each other. 3. Eight prey-derived proteins that elicit attack by garter snakes (Thamnophis sirtalis) from earthworms (Lumbricus terrestris) were analyzed with these antibodies, and can be assigned to three distinct groups on the basis of their antigenic properties. 4. Unfolding or denaturation of the low molecular weight protein did not alter its antigenic activity to its polyclonal antibodies, suggesting the antigenic epitopes contain contiguous amino acid sequences. 5. In contrast, unfolding of the 20,000 mol. wt protein resulted in a loss of its binding with antibodies, suggesting that the epitope of this protein contains noncontiguous amino acid sequences. 6. The snake-attractivity of the 20,000 mol. wt protein could not be neutralized by reacting it with its antiserum, suggesting that the antigenic determinant (the epitope) of the antigen is not an integral part of the attractive domain of the ES20 protein. 7. In contrast, the attractivity of the purified low molecular weight protein could be neutralized by the polyclonal antibodies. PMID- 1611879 TI - Evaluation of immunochemical changes in ovalbumin due to reaction with oxidizing methyl linoleate by an enzyme linked immunosorbent assay. AB - 1. An enzyme linked immunosorbent assay (ELISA) was used to study the immunochemical properties of ovalbumin altered by the reaction with oxidizing methyl linoleate under various conditions. 2. The results indicated that the values of ELISA decreased with an increase of the degree of ovalbumin following reaction with oxidizing methyl linoleate. 3. The antigenicity of ovalbumin, when examined by competitive inhibition assay, reduced about 20-fold as compared with native ovalbumin when reacted with oxidizing methyl linoleate at 50 degrees C and water activity (0.68) for 30 days. PMID- 1611880 TI - Purine metabolite concentrations in portal and peripheral blood of steers, sheep and rats. AB - 1. The concentration of purine derivatives in portal and peripheral blood of steers, sheep and rats was measured by reverse-phase high performance liquid chromatography. 2. Nucleotides, nucleosides (apart from inosine), adenine and guanine were not found in the plasma samples. Allantoin, uric acid, hypoxanthine and xanthine accounted for virtually all purine metabolites in plasma samples. 3. Non-oxidized derivatives (hypoxanthine and xanthine) were consistently detected in sheep but not in steer or rat plasma samples showing a differential availability of reutilizable purine derivatives between species. PMID- 1611881 TI - Liver metabolism of cholesterol taken up from lipoproteins in Wistar rats. An in vivo comparison between rat and human lipoproteins. AB - 1. This study compares liver uptake, biliary secretion and blood decay of VLDL, LDL, HDL2 and HDL3 lipoprotein fractions isolated from both rat and human plasma and labelled with [14C]-cholesterol following the i.v. administration to the bile fistulated rat model. 2. The present results demonstrate that the use of heterologous lipoproteins in bile-fistulated rat can be helpful in administering in a small volume large amounts of free and esterified cholesterol and in evaluating specific aspects of lipoprotein cholesterol metabolism by liver. PMID- 1611882 TI - A comparison of human and porcine platelet fatty acid composition. AB - 1. Human and pig platelets were analyzed for lipid composition by gas chromatography. 2. In comparing the two species' platelets, we noted significant differences in several lipid concentrations, some of which involved major lipid constituents. 3. The lipids for which there are significant differences in composition may contribute to those variations in platelet responses to stimulation demonstrated to exist between species. PMID- 1611884 TI - Immunochemical studies of histone H5 from Halobatrachus didactylus. AB - 1. Histone H5 from Halobatrachus didactylus was isolated by using perchloric acid (PCA) extraction of fish liver nuclei and trichloroacetic acid (TCA) precipitation. 2. A polyclonal antiserum was generated by immunizing rabbits with the antigen purified from SDS-PAGE. 3. By immunofluorescence the serum stains erythrocyte nuclei from H. didactylus but it does not react with mammalian cells. 4. By Western blotting, the anti-H5 antibody reacts with the isolated antigen at high titers. 5. Digestion of histone H5 with pepsin and cyanogen bromide suggests that the epitopes are located in the globular and C-terminal region of the H5 molecule excluding the N-terminal. PMID- 1611883 TI - Analysis of porcine gastric mucus glycoprotein added to a culture medium of Streptomyces sp. OH-11242 as the only source of carbon. AB - 1. In the process of obtaining the degradation enzymes of mucus glycoprotein, porcine gastric mucus glycoprotein (PGM), added as the only source of carbon, was removed from the culture medium of Streptomyces sp. OH-11242 [Iwase et al. (1988) Biochem. biophys. Res. Commun. 151, 422-428] and analysed. 2. The amino acid and carbohydrate compositions of porcine gastric mucus glycoprotein (PGM-m) recovered from a culture medium were similar to those of original PGM. 3. However, the elution profile of PGM-m on Sephacryl S-400 differed from that of PGM and closely resembled that of performic acid-treated PGM or protease-treated PGM. 4. Either of these corresponded to the so-called subunit of approximately 550,000 in mol. wt, as reported by Scawen and Allen [(1977) Biochem. J. 163, 363-368]. 5. Performic acid treatment of PGM-m led to the production of a smaller unit (unit m) having a mol. wt of about 72,000. Separate treatment of different sized components prepared from PGM-m showed the above unit m to be produced from each molecule. 6. Thus, PGM-m is a molecule partly modified by various glycosidases including endo-alpha-N-acetylgalactosaminidase and exposure of the modified part to performic acid results in oxidation. 7. Production of unit m from both larger and smaller molecules indicates the part susceptible to performic acid to exist at regular intervals on the mucus glycoprotein molecule.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611885 TI - Comparison of the hemoglobins of the platyhelminths Gastrothylax crumenifer and Paramphistomum epiclitum (Trematoda: Paramphistomatidae). AB - 1. Gastrothylax crumenifer and Paramphistomum epiclitum parasitize the water buffalo Bubalus bubalis. 2. Gastrothylas hemoglobin consisted of two fractions of ca 30,000 and ca 18,000 by gel filtration. SDS-electrophoresis showed both to be single, ca 15,000 chains. 3. Paramphistomum hemoglobin was ca 16,000 by both gel filtration and SDS-electrophoresis. 4. Reversed-phase chromatography of carboxymethylated trematode and buffalo globins gave single peaks and two peaks, respectively. Although Paramphistomum hemoglobin provided and N-terminal sequence, Gastrothylax hemoglobin did not, suggesting blocked N-terminals. The buffalo sequences were found to be identical to the sequences of the alpha and beta chains of bovine hemoglobin. 5. Although Paramphistomum hemoglobin consists of only one chain, Gastrothylax hemoglobin consists either of one chain which aggregates to a dimer or of two different chains, only one of which aggregates to a dimer. PMID- 1611886 TI - Monoclonal antibody to alkaline phosphatase from the intestinal mucosa of the harp seal, Phoca groenlandica. AB - 1. Hybridoma secreting a monoclonal antibody APP.1 to the harp seal alkaline phosphatase (A1Ph) was obtained by fusing murine myeloma Sp 2/0 cells with the splenocytes of BALB/c mice immunized with purified isozyme K. 2. The antibody has no effect on the enzyme activity and shows a high affinity for harp seal A1Ph (KD = 8.5 x 10(-10) M). The antibody has similar affinities for the AlPh of harp seal, fur seal, common seal and deer. 3. The antibody APP.1 was coupled to Sepharose and employed in chromatographic purification of the harp seal intestinal AlPh. Alkaline phosphatase isolated on this immunosorbent has a spec. act. of 20,800 units per mg of protein. 4. The antibody-enzyme complex gives an excellent immunocytochemical labeling of tissue sections, cell cultures and smears. PMID- 1611887 TI - A flow procedure to determine oxygen binding isotherms for low affinity and easily oxidized hemoglobins. AB - 1. The determination of binding isotherms for low affinity hemoglobins is particularly difficult because of rapid autoxidation. 2. In carp Hb (pH 6 + IHP, 25 degrees C), one-quarter of the hemes are oxidized within 3 min, preventing the accurate determination of even P50 or X. 3. We circumvent this problem by rapidly flowing HbO2, initially at pH 9 (X = 1.4 microM), against a low pH buffer to bring the system rapidly to equilibrium in the low affinity form. Diode-array spectrophotometry allows a complete spectrum to be obtained less than 5 sec, after flow ceases, before significant oxidation has occurred. In tandem with the stopped flow apparatus is an oxygen electrode to measure O2 activity. 4. At 22 degrees C, the half-saturation oxygen activity (X) is 227 microM, and the Hill number is 0.91, for carp Hb (T state) implying significant differences in the O2 affinities of the alpha and beta chain hemes or, two different T states. PMID- 1611888 TI - Computer visualization of left ventricular geometry during the cardiac cycle. AB - Mathematical expressions regulating ventricular dimensions during the cardiac cycle have been defined. Classical, static images are limited in comparison with ventriculograms, are not intuitive for teaching, and do not effectively convey effects of hypertrophy or dilatation. Accordingly we developed Tachycardia, an interactive menu-driven graphics program. The program allows three-dimensional visualization of the kinetics of the thick-walled, ellipsoidal left ventricle (LV). The user may specify mass, ejection fraction, end-diastolic volume, major to minor axis ratio, and diastole to systole time ratio. Real-time animation of heart rates ranging from 50-150/min is achieved. A library contains animations representing the normal LV, including dilatation and concentric or eccentric hypertrophy. For comparison of differences in LV geometry among ventricles, multiple animations can be viewed simultaneously. We conclude that computerized animation provides an intuitive understanding of the dynamic geometry of the cardiac cycle. User definition of the visualization can provide clinical utility and teaching value. PMID- 1611889 TI - Automated detection and classification of breast tumors. AB - This paper presents a new method for the mammographic detection and classification of two types of breast tumors, stellate lesions and circumscribed lesions. The method assumes that both types of tumors appear as approximately circular, bright masses with a fuzzy boundary and that stellate lesions are in addition surrounded by a radiating structure of sharp, fine lines. Experimental results for a set of 27 mammograms are presented and the method is shown to have a high detection rate and an extremely low false positive rate. PMID- 1611890 TI - As we may think: the concept space and medical hypertext. AB - Hypertext, a medium for presenting written material in a nonsequential manner, is gaining popularity as a format for medical text. The structure of "traditional" hypertext documents (hyperdocuments) includes author-created links among text segments. This structure poses challenge for those who create and maintain hyperdocuments, while reading them can introduce disorientation and cognitive overload. An alternative model is presented in which text segments are linked to the concepts which they contain and the concepts are linked to each other in a semantic network called the "Concept Space." The concepts and semantic links attempt to approximate potential topics of interest, allowing the reader to browse the hyperdocument in an individualized manner, rather than in an author designated one. The concept space approach offers advantages for both the author and the reader. PMID- 1611891 TI - Simulation of ozone uptake distribution in the human airways by orthogonal collocation on finite elements. AB - Ozone transport in a rigid single-pathway anatomic model of the lung was analyzed by a stable convergent numerical algorithm, the method of orthogonal collocation on finite elements. The simulations predicted the dynamic behavior of gas phase concentration profiles for both ozone and an insoluble inert gas. An internal quasi-stationary diffusion front was observed during early inspiration for both gases. In addition, the absorptive distribution of ozone in lung airways was computed as a total dose as well as a tissue dose. The total dose of ozone decreased along the airway path from the mouth. However, the tissue dose of ozone increased along the conducting airways, reached a maximal dose in the terminal bronchioles, and decreased sharply in the respiratory airways. PMID- 1611892 TI - Scaling up the nervous system of Caenorhabditis elegans: is one ape equal to 33 million worms? AB - Although vastly different, both the mammalian brain and the nematode Caenorhabditis elegans' nervous system must contribute critically to assure survival. Two quantitative conditions which place bounds on networks for connectedness and stability are tested on the published neural network of C. elegans and fit. Consideration of networks scaled up to mammalian size and confined between these bounds suggests that perhaps, the entire spectrum of brain size may be built between these bounds. Further consequences of increasing brain size relate to the trade-off between complexity, providing internal resistance to individual damage, and redundancy of population, as survival mechanisms. PMID- 1611893 TI - Development of a knowledge base for diagnostic reasoning in cardiology. AB - This paper reports on a formative evaluation of the diagnostic capabilities of the Heart Failure Program, which uses a probability network and a heuristic hypothesis generator. Using 242 cardiac cases collected from discharge summaries at a tertiary care hospital, we compared the diagnoses of the program to diagnoses collected from cardiologists using the same information as was available to the program. With some adjustments to the knowledge base, the Heart Failure Program produces appropriate diagnoses about 90% of the time on this training set. The main reasons for the inappropriate diagnoses of the remaining 10% include inadequate reasoning with temporal relations between cause and effect, severity relations, and independence of acute and chronic diseases. PMID- 1611895 TI - Mucocele as a complication of colostomy closure. PMID- 1611894 TI - Liver transplantation for acute fulminant hepatic failure. AB - Orthotopic liver transplantation (OLT) remains the only option for progressive acute fulminant hepatic failure (FHF). The overall one-year survival is approximately 58% versus 75% for all patients undergoing OLT. Nevertheless, this is superior to the results obtained with medical management alone, which carries a mortality of approximately 60-85%. Seven of 32 patients at Hartford Hospital (22%) received liver transplants for acute FHF; the one-year survival was 57%. Four of seven patients are alive with complete neurologic recovery. One case is presented in detail. PMID- 1611896 TI - From consumption to tuberculosis in Connecticut. David R. Lyman. 1942. PMID- 1611897 TI - Suggestions for health care cost control. PMID- 1611898 TI - Suggestions for health care cost control: an alternative point of view. PMID- 1611899 TI - Treatment of choice for gonorrhea in Connecticut. PMID- 1611901 TI - The physicians of America--divided and very vulnerable. PMID- 1611900 TI - Ofloxacin vs ciprofloxacin: a comparison. AB - Ofloxacin and ciprofloxacin are fluoroquinolones with similar characteristics. However, important differences can be observed in their antimicrobial activity, clinical utility, and pharmacokinetic and interaction profiles. Ofloxacin is more active in urethral chlamydia infections; it also may more effectively eradicate staphylococcal infections and Streptococcus pneumoniae pulmonary infections. Furthermore, ofloxacin does not significantly alter theophylline concentrations. Ciprofloxacin has better activity against gram-negative bacilli, an advantage which may be negated by ofloxacin's longer half-life and higher serum levels. Therefore, while both drugs are effective as treatment of infections due to gram negative organisms, ofloxacin is also appropriate in the treatment of: 1) infections where both aerobic gram-negative rods and staphylococci or S. pneumoniae are documented or suspected, 2) urethritis, particularly when C. trachomatis is documented or suspected, 3) infections in patients concomitantly receiving theophylline. PMID- 1611902 TI - Eli Ives 1779-1861. PMID- 1611903 TI - Moving beyond futility. PMID- 1611904 TI - Conflicting regulations: Public Act 91-168. PMID- 1611905 TI - Dr. Creighton Barker. Distinguished, or just prejudiced? PMID- 1611906 TI - Distribution of satellite DNA fractions within major heterochromatic regions of human chromosomes as revealed by PleI and TfiI digestion. AB - Banding patterns induced by selective DNA extraction with the restriction endonucleases PleI and TfiI reveal the distribution of human satellite DNAs within the major heterochromatic blocks on human metaphase chromosomes. PleI and TfiI are able to discriminate HinfI target sites, depending on the nature of the central base. PleI digestion specifically reveals regions, within major C-bands, that include the major sites of satellite II DNA and permits more precise localization of satellite II domains than does radioactive in situ hybridization. The close correspondence between the cytogenetic results presented here and previously reported molecular data seems to support the idea that the frequency of enzyme target sequences is the main factor in determining the action produced by restriction endonucleases on fixed human chromosomes and that chromatin conformation is not an important factor in limiting enzyme accessibility. PMID- 1611908 TI - Genetic linkage analysis places locus DXS250 between locus DXYS1 and locus DXS3 in Xq21.3. AB - The locus DXS250, which is linked to the Allan-Herndon type of X-linked mental retardation, maps between DXS3 and DXYS1 in a panel of 40 families established by the Centre d'Etude du Polymorphisme Humain, Paris. PMID- 1611907 TI - Expression of decorin in human tissues and cell lines and defined chromosomal assignment of the gene locus (DCN). AB - Earlier studies had shown that the expression of the gene coding for one eminent connective tissue proteoglycan, decorin (DCN), is deficient in the fibroblasts of 3 out of 15 Marfan patients (Pulkkinen et al., 1990). To obtain more information on the expression of this gene, various human tissues and cell lines were studied. High mRNA levels of decorin were detected in aorta, lung, skin, kidney, smooth muscle, and placenta, whereas significantly lower mRNA levels were found in the rest of the tissues analyzed. Two sizes of transcripts were observed in all tissues. The two transcripts of decorin most probably do not represent two different genes, since in situ hybridization gave only one strong signal, placing the gene in 12q21----q22. No tissue-specific differences in the two mRNA species of decorin were detected. This is in contrast to the gene of versican, another connective tissue proteoglycan gene, that was analyzed as a control; high expression of a longer transcript of the versican gene was found in brain and smooth muscle, whereas the shorter transcript was predominant in all other tissues studied. DCN was actively transcribed in cultured mesenchymal cells, whereas in cells of endothelial or epithelial origin, the transcription level was undetectable. These tissue- and cell type-specific variations in the expression of DCN may help to explain the complex phenotypic variation typical of individuals with Marfan syndrome. PMID- 1611909 TI - Localization of the 5' end of the MCF2 oncogene to human chromosome 15q15----q23. AB - Oncogenic activation of the MCF.2 cell line-derived transforming sequence gene (MCF2) occurs through substitution of part of its 5' coding region by unrelated nonsyntenic sequences. Analysis of the MCF2 oncogene locus revealed complex recombination events involving four discontinuous human DNA segments. The upstream replacing sequence, named URS, represents the farthest 5' portion of the locus. The URS sequence maps to the D15S93 locus on human chromosome 15q15--- q23. PMID- 1611911 TI - Genetic mapping and assignment of a long-range repeat cluster to band D of chromosome 1 in Mus musculus and M. spretus. AB - A cluster (D1Lub1) of a long-range repeat family was mapped to the proximal part of the Giemsa-negative band D in Chromosome 1 of Mus musculus and M. spretus by in situ hybridization with cloned probes of the long-range repeat family. By making use of restriction fragment length polymorphisms in DNAs from interspecific backcross mice, the cluster could be mapped to a position 5.3 +/- 2.1 cM distal to the Inha locus and the same distance proximal to the Bcl-2 locus. D1Lub1 was inseparable in 114 meiotic events from Acrg, Sag, and Akp-3. Taken together, the data may serve as a reference for coordinating the genetic and cytogenetic maps of Mus Chromosome 1. High-copy-number variants of the cluster, which appear cytogenetically as homogeneously staining regions at the same chromosome location, presumably arose by amplification of the long-range repeat family in situ. PMID- 1611910 TI - The human protein-tyrosine phosphatase PTP alpha/LRP gene (PTPA) is assigned to chromosome 20p13. AB - In situ hybridization was employed to localize a cDNA probe from the human protein-tyrosine phosphatase PTP alpha/LRP to human metaphase chromosomes. The PTPA gene has been localized to chromosome 20p13. PMID- 1611912 TI - Heterosynapsis and axial equalization of the sex chromosomes of the northern bobwhite quail. AB - The pairing behavior of the Z and W chromosomes in the female northern bobwhite quail (Colinus virginianus) was analyzed by electron microscopy of silver-stained synaptonemal complexes (SCs). After autosomal pairing was completed, synapsis of the sex chromosomes initiated at the short-arm end of the W chromosome and one end of the Z chromosome. Synapsis then progressed unidirectionally, producing a sex bivalent in which the entire length of the W axis was paired with an equivalent length of the Z axis. Progressive contraction and asymmetrical twisting of the Z axis ultimately resulted in a fully paired configuration with aligned axial ends. Further contraction of the Z axis reduced the extent of asymmetrical twisting such that only the nonaligned centromeric regions distinguished the SC of the ZW bivalent from SCs of similar-sized autosomes in late-pachytene nuclei. Quantitative analyses indicated that the length of the Z axis shortened significantly during the adjustment process, whereas no significant difference occurred in the length of the W axis. The nonalignment of the centromeric regions during transitional stages of ZW synapsis indicates that direct heterosynapsis of nonhomologous segments, followed by axial equalization of the length inequality, is responsible for the length adjustment during synapsis in the sex chromosomes of the bobwhite quail. PMID- 1611913 TI - Evidence for genetic etiology of heteroploidy in embryos of the Japanese quail (Coturnix coturnix japonica). AB - The Japanese quail was used as an experimental system to detect the effects of genes that affect chromosome behavior and distribution. From a random-bred population, three inbred generations were produced by full-sib matings in 36 families. The expectation from such a breeding scheme was that embryos bearing aberrations induced by recessive mutant genes would cluster within families and recur in particular lineages. Chromosomal aberrations caused by errors during fertilization, cleavage mitosis, and gametogenesis were scored in 2,037 16- to 18 h embryos from 107 families. Comparisons of the observed frequencies among families and lineages and pedigree analysis indicated that four types of chromosome aberrations had a genetic basis: (1) triploidy and triploid chimerism; (2) haploidy and haploid chimerism; (3) diploid/tetraploid mosaicism; and (4) a new aberration, referred to as "atypical mitotic metaphase." Analysis of the sex chromosome complements of the embryos indicated that triploidy resulted predominantly from diploid ova, haploid cell lines originated from supernumerary sperm nuclei, and tetraploid cell lines resulted from endoreduplication or failure of cytokinesis. Clustering of triploidy in particular lineages was due to dispermy or recurrent suppression of one or both meiotic divisions during oogenesis. PMID- 1611914 TI - Meiotic delay of mouse spermatocytes carrying x-ray-induced translocations. AB - The kinetics of spermatocyte progression through meiotic prophase in cells with or without induced translocations were studied in mice that had been exposed to x rays. Pulse-labeling experiments using 3H-thymidine, followed by autoradiographic analysis, indicated that at higher x-ray doses (6 and 7 Gy), translocation carrying cells tend to spend more time in meiotic prophase than do normal cells. At 2 Gy, no such delay seemed to be present. The observed delay may explain the reduction in transmission of translocations to the next generation reported by others. PMID- 1611915 TI - Heterochromatin characterization of sex chromosomes in Triturus marmoratus (Urodela, Salamandridae). AB - The sex chromosomes of the Iberian marbled newt, Triturus marmoratus, were studied using various banding techniques, including restriction enzyme/nick translation (RE/NT) procedures. Four types of heterochromatin on the sex chromosomes could be distinguished: (1) distamycin A/DAPI and chromomycin A3/distamycin A positive, EcoRI/NT negative, and HaeIII/NT and HinfI/NT positive; (2) distamycin A/DAPI and chromomycin A3/distamycin A positive, but RE/NT negative; (3) AT rich, but RE/NT negative; and (4) distamycin A/DAPI and chromomycin A3/distamycin A positive, EcoRI/NT and HinfI/NT negative, but HaeIII/NT positive. These data suggest a common origin for the terminal heterochromatic domains of both the X and Y chromosomes in this species. PMID- 1611916 TI - Induction of R-bands on human chromosomes by TfiI as the consequence of local differences in target richness. AB - We present a new restriction enzyme-banding pattern on fixed human chromosomes. R bands are induced by TfiI, an enzyme that cuts DNA at GA(A/T)TC, that is, at HinfI sites having A or T in the central position. Results suggest that regional differences in the frequency of targets are responsible for the effect caused by this enzyme, whereas conformational differences between G- and R-bands would not affect the enzyme action. PMID- 1611917 TI - Infertility in human males with autosomal translocations. II. Meiotic studies in three reciprocal rearrangements, one showing tertiary monosomy in a 45-chromosome individual and his father. AB - The meiotic prophase behavior of three human reciprocal autosomal translocations is presented. Each translocation was ascertained among men attending an infertility clinic. Two involved chromosomes 3 and 5, with breakpoints in different places. Quadrivalents were seen in every cell. The third translocation was a rare t(11q;15q) rearrangement in a 45-chromosome individual with tertiary monosomy. The long product of the translocation was retained in the karyotype over two generations of the family, the short product having been lost. At meiotic prophase, a trivalent was seen in every cell; in 60% of the nuclei, the short arm of the trivalent was closely associated with the XY bivalent. The transmission and phenotypic effects of tertiary monosomy in man and the mouse are discussed. PMID- 1611919 TI - Pancreatic tissue fluid pressure and pain in chronic pancreatitis. AB - A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously reported have been confirmed, and pressures are normal or only slightly elevated in patients without pain. It seems evident that a substantial pressure decrease during drainage operations leads to freedom of pain. The pancreatic tissue fluid pressure elicits considerable regional differences in patients with painful chronic pancreatitis. These differences are significantly larger across a stenosis in the duct than across normal duct, but there is no significant relation between pressure and duct diameter. The median pressure is significantly related only to cavities in the pancreas, but not to ERP-findings, calcifications or residual pancreatic exocrine function. Drainage operations cause an overall pressure decrease of approximately 50%, the end pressure being slightly but not significantly elevated compared to normal but with considerable inter- and intraindividual variation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1611918 TI - The platelet-vessel wall interaction in experimental atherosclerosis and ischaemic heart disease with special reference to thrombopoiesis. AB - Platelets and their interaction with the vessel wall play a role in atherogenesis and in the formation of the coronary thrombus. Supplementation of the diet with n 3 PUFA shifts the platelet-vessel wall interaction in anti-thrombotic direction in healthy persons and in patients with IHD. This is in part caused by an inhibition of Tx synthesis and also by an increased synthesis of PGI2 and PGI3 in the vessel wall. However, the clinical significance of these findings needs to be elucidated in clinical trials. Large, dense platelets are more reactive than small ones. Platelet size and density are determined at thrombopoiesis. Large, reactive platelets have in states with an increased platelet demand been shown to be produced from large, high-ploidy megakaryocytes. In patients with thrombopoiesis in steady-state an inverse relation between the bleeding time and both the DNA content and the size of the bone marrow megakaryocytes has been demonstrated. The bone marrow megakaryocytes in these patients were larger in men than in women, which may explain the sex difference in bleeding time observed by others. In experimental atherosclerosis changes in megakaryocyte size have been demonstrated. The significance of these changes are still unclear. In a single study stimulation of the platelet-megakaryocyte axis was associated with an acceleration of experimental atherosclerosis. This study suggests that large, high ploidy megakaryocytes may produce a large amount of atherogenic platelets that may be responsible for the increased formation of atheroma in this model. However, due to the complexity of the study design this hypothesis needs verification in other experimental and clinical studies. In patients suffering from an AMI the mean platelet volume is increased. The bleeding time is shortened at the time of infarction in these patients probably due to increased synthesis of TxA2, but an increased production of adrenaline may also be of importance. These large, reactive platelets present in AMI may be a reflection of an altered thrombopoiesis in these patients. It remains to be established whether these changes in platelet reactivity are present before the time of coronary thrombus formation. PMID- 1611921 TI - Interactions between Yersinia enterocolitica and the host with special reference to virulence plasmid encoded adhesion and humoral immunity. AB - This thesis is based on 8 publications and a review of the literature. The aim was to summarize present knowledge on molecular components of Yersinia enterocolitica involved in (i) adhesion, with special reference to plasmid encoded factors and (ii) induction of antibodies in the host, and the quantitation of these two phenomena. Adhesion of Y. enterocolitica was quantitatively studied by methods that measured binding to cultured epithelial cells, mucosal constituents immobilized on polystyrene, intestinal tissue, and nonbiological solid surfaces. The chromosomal inv and ail gene products have been shown by others to be independently able to mediate adhesion to and invasion of cultured epithelial cells. However, the Yersinia virulence plasmid, pYV, also encodes for at least one product that may mediate adhesion. It was shown that pYV carrying Y. enterocolitica strains adhered more efficiently than their isogenic pYV cured derivatives to rabbit and human ileal intestinal tissue and to rabbit ileal brush border membrane vesicles (BBVs). Using Y. enterocolitica mutants that were defective for production of the pYV encoded outer membrane protein, YadA, and Escherichia coli strains carrying the cloned yadA gene it was verified that YadA was responsible for the pYV encoded adhesion. The YadA promoted adhesion was found likely to be non-specific and, at least in part, mediated by hydrophobic interaction. YadA, however, also mediated binding to one or more constituents present in intestinal mucus. Such binding led to decreased ability to penetrate a layer of mucus in vitro and subsequent decreased ability to adhere to BBVs. Based upon these results, it remains uncertain whether Y. enterocolitica is able to benefit from the YadA mediated adhesion in the intestinal millieu. In vivo results have suggested that expression of YadA confers on Y. enterocolitica an increased ability to colonize the intestine, but no definitive conclusions have been reached so far. A large number of antigens were identified in Y. enterocolitica by means of crossed immunoelectrophoresis (XIE). Quantitation of serological cross-reactions between chromosome-encoded Y. enterocolitica antigens and antigens from other bacterial species was performed by means of XIE and proved useful for taxonomic purposes. Using XIE it was shown that infection with Y. enterocolitica induced an antibody response against a wide range of antigens. Tube agglutination, enzyme linked immunosorbent assays (ELISAs) using purified lipopolysaccharide (LPS) or formalin-killed whole pYV carrying cells as antigens, and XIE were evaluated for their applicability to detect recent Y. enterocolitica O:3 infection.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611920 TI - Dynamic aspects of the tubuloglomerular feedback mechanism. AB - Tubuloglomerular feedback (TGF) is an important intrarenal regulatory mechanism, which acts to stabilize renal blood flow, GFR, and the tubular flow rate. The anatomical basis for this negative feedback system is the Juxtaglomerular Apparatus (JGA). This is located at the point of contact between the thick ascending limb of the loop of Henle (TAL) and the vascular pole of the glomerulus. The JGA includes the macula densa, a specialized plaque of cells in the TAL thought to be responsible for the sensing step in the feedback mechanism; the mesangial cells, a cushion of cells separating the macula densa from the vascular pole of the glomerulus; and the afferent arteriole, the main effector site for the TGF. An increase in the NaCl concentration at the macula densa elicits a response in the smooth muscle cells of the afferent arteriole increasing the hemodynamic resistance of the preglomerular vasculature. These changes will, through decreases in the GFR and the tubular flow rate, cause a decrease in the NaCl concentration at the macula densa. Thus, the system acts to stabilize the NaCl concentration at the macula densa. The purpose of the present study was to describe the dynamic characteristics of the TGF, and to use this knowledge in elucidating the role of the TGF system in the autoregulation of renal blood flow. Further, by comparing the dynamic characteristics of TGF between hypertensive and normotensive rats, to identify possible alterations in renal function that could play a role in the etiology and pathogenesis of hypertension. Anesthesia and surgery are unavoidable complications in experimental work in animals. It is shown that the anesthetics commonly used in micropuncture experiments in rats have different effects on various aspects of renal function, e.g. GFR, sodium excretion, proximal tubular compliance, and TGF function. It is concluded that the thiobarbiturate inactin, the most used anesthetic, has more detrimental effects on renal function than halothane and other barbiturates. In halothane anesthetized rats, the proximal tubular pressure oscillates with a frequency of 30-50 mHz. The pressure oscillations are associated with oscillations in tubular flow, and the early distal tubular Cl- activity. The possible mechanisms behind the oscillations are discussed. It is concluded that the oscillations appear because of the operation of the TGF system. Although it seems unlikely, it cannot be excluded that a vascular pacemaker is involved in the underlying oscillatory mechanism. To test the hypothesis that the oscillations are caused by the TGF system, a series of dynamic mathematical models of the TGF system have been developed.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1611923 TI - Prognostication in acute myocardial infarction by early echocardiographic estimation of left ventricular ejection fraction. Multivariate statistical comparison with a clinical prognostic index and its components. AB - The purpose of this study was to define the prognostic value concerning in hospital, two-month, and one-year mortality of an early echocardiographic estimation of left ventricular ejection fraction, relative to traditional clinical variables and a clinical prognostic index, in an unselected series of 193 patients following acute myocardial infarction. Left ventricular ejection fraction was determined within 72 hours by echocardiographic wall motion analysis within the frame of a nine-segment model. Clinical variables (age, number of acute myocardial infarctions, reinfarction, heart failure, cardiac arrest, ventricular arrhythmias, asystole, supraventricular tachycardia, nodal rhythm) and a calculated, previously published index, based on these variables, were recorded on day five post infarction and predischarge. The Killip class was recorded at the time of echocardiography. All variables were compared by a multivariate approach (Cox regression model). The results showed that left ventricular ejection fraction was the strongest predictor of early and late mortality and increasingly so over the period of observation. Age and maximal Killip class had a modest additional prognostic value, whereas the composite clinical prognostic index had no predictive power when early left ventricular ejection fraction was included in the statistical model. PMID- 1611922 TI - Lung cancer risk and social class. The Copenhagen Male Study--17-year follow up. AB - The Copenhagen Male Study is a prospective cohort study initiated in 1970/71 comprising 5249 employed men between the ages of 40 and 59 years. Included in a registry follow up of lung cancer were 4931 men who responded sufficiently to a number of questions on tobacco habits and who could be classified into social classes. During the 17 years of follow up, lung cancer was diagnosed in 144 men. By the end of the follow up period, 135 had died. Substantial social inequalities in the risk of lung cancer were found with a gradually increased risk with low social class, Kendall's tau B = 0.07, p less than 0.001. In multivariate analysis, compared with the highest social class (highly educated, administrators), the lowest social class (unskilled workers), had a highly increased risk, relative risk (with 95% confidence limits), RR = 3.7 (1.9-7.3). If in the analysis, adjustments were made for form of smoking, amount smoked, whether inhalation took place, number of pack-years and age, the increased risk dropped to RR = 2.9 (1.5-5.9). We conclude that the substantial social inequalities in lung cancer risk are only to a minor degree explained by social class differences in tobacco smoking habits. PMID- 1611924 TI - HIV infection among intravenous drug users in Copenhagen. AB - From October 1985 until the end of December 1986, 439 intravenous drug users (IVDU) presented themselves at the outpatient venereal disease clinic of Copenhagen for an HIV-test. HIV-antibodies were found in 53 out of 272 men (19.5%) and in 25 of 167 women (15.0%), giving an overall prevalence of 17.8%. Risk factors for HIV were the length of drug abuse (p less than 0.05) and having injected drugs within the last six months before testing (p less than 0.005). HIV antibodies were found in 18 of 90 women (20%) and in three of 20 men (15%), who had a history of a past or ongoing life as a prostitute. The IVDU in this study have been chosen as a cohort and recalled for an ongoing follow-up study focusing on drug and sexual behaviour in relation to the initial HIV-test result. PMID- 1611925 TI - Burst abdomen--clinical features and factors influencing mortality. AB - The hospital records of 198 patients with wound dehiscence following gastrointestinal surgery were reviewed (median age 66 years, male:female ratio 2.5:1). The median time from primary surgery to wound dehiscence was six days (1 24 days). The postoperative course prior to dehiscence was uneventful in half of the patients, and two-thirds had evidence of bowel function. The overall mortality rate following dehiscence was 24%. The most common cause of death was cardiorespiratory insufficiency (58%) and peritoneal sepsis (15%). Factors without influence on mortality were: 1) Complicating illness prior to surgery. 2) Primary disease. 3) Emergency surgery. 4) Contamination of the wound. 5) Postoperative complications prior to rupture. 6) Absence of bowel function. 7) Complete or incomplete rupture of the wound. Mortality, however, was higher in females, in patients with longitudinally versus transverse incisions, and in elderly patients. Late incisional hernia or sinus reactions occurred in 34 patients (23%). PMID- 1611926 TI - Hypothermic patients admitted to an intensive care unit: a fifteen year survey. AB - In the period 1975-1989, 620 (4.5%) of 13,645 patients admitted to the intensive care unit of a Danish university hospital were diagnosed as suffering from hypothermia. The aim of the retrospective survey carried out is to describe this group of patients and to evaluate the methods used for rewarming. The degree of hypothermia was mild in 554 of the patients, moderate in 60, and severe in six. The rewarming method used was passive rewarming with the use of endogenous heat production. Rewarming was established with a median temperature increment of 0.1 to 2.5 degrees centigrade. The mortality rate showed no relationship to the hypothermia. With the exception of extracorporal circulation, the rewarming and mortality rates did not differ from the results shown in studies carried out using active and invasive rewarming procedures. In conclusion, with the exception of extracorporal circulation, rewarming of hypothermic patients by preservation of the endogenous heat production seems as effective as active and invasive rewarming methods. PMID- 1611927 TI - Prediction of later hyperbilirubinaemia by measurement of skin colour on the first postnatal day and from cord blood bilirubin. AB - The study comprised 138 mature and healthy newborns admitted to the newborn nursery. The performance of cord bilirubin, yellow skin colour on the first postnatal day, and the increase in skin colour during the first postnatal day was evaluated as a test for later hyperbilirubinaemia, defined as a serum bilirubin concentration above 200 mumol/l on the third postnatal day. All three tests performed well as tests for later hyperbilirubinaemia and had closely similar receiver operating characteristic curves. Combination of the three tests by the technique of logistic regression showed an even better test performance, and it was found that each single parameter contributed significantly to the prediction. PMID- 1611928 TI - Perinatal audit. Are experts biased by knowledge of outcome? A controlled study. AB - Perinatal audit is a method widely used for quality assurance in medicine. In clinical medicine, experiments have revealed that physicians' prior knowledge and expectations may bias their assessments. This study examined whether experts in perinatal audit were biased in their evaluation of perinatal and neonatal care when they had knowledge of the outcome. A panel of experts evaluated the quality of care in 48 infants who died in the neonatal period and 48 paired infants who survived it. The 48 pairs were randomly allocated to two groups. In the first group, the outcome of neonatal death or neonatal survival appeared in the case histories, whereas in the second group the outcome was blind. There were no differences in the assessment of quality of antenatal, delivery, and neonatal care comparing the result of the evaluation between the cases with knowledge of the outcome and the cases without knowledge of outcome. Our results indicate that the experts were not biased by the knowledge of outcome when they assessed the quality of peri- and neonatal care. PMID- 1611929 TI - Prostaglandin E2 in intestinal secretion with special reference to methodological problems in vivo and in vitro. PMID- 1611930 TI - Antifungal prophylaxis during neutropenia or allogeneic bone marrow transplantation: what is the state of the art? Ad HOC Working Group. AB - Neutropenia induced by intensive chemotherapy and allogeneic bone marrow transplantation are increasingly commonly complicated by fungal infections; thus prophylaxis may be justified. The authors surveyed the literature and culled their experience - few randomized trials have been done and definitions have often been poor. In prophylaxis of mucosal candidosis, miconazole and clotrimazole may both be more effective than placebo. Nystatin is ineffective and ketoconazole of medicine efficacy. Fluconazole is effective at 50 mg/day and 400 mg/day. Itraconazole and amphotericin B both need further evaluation. In prevention of systemic candidosis, oral nystatin prophylaxis, up to 4 X 10(6) U/day, is usually unsuccessful, though compliance is variable. Oral amphotericin B in low doses is ineffective, but 50 mg or more 4 times daily may prevent systemic candidosis, though compliance is variable. Oral ketoconazole, 400-600 mg/day, is possibly effective prophylaxis in neutropenia but not after bone marrow transplantation; liver function (often abnormal in these patients) is a problem, as is tolerability. Oral fluconazole is well tolerated, has reliable serum concentrations and is effective following bone marrow transplantation, but the optimum dose is uncertain. In bone marrow transplantation, intravenous amphotericin B, 0.1 mg/kg/day, appears to be effective; there are no data in neutropenia. Oral itraconazole (capsules, 200 mg/day) may be active; data are scanty. In prevention of invasive aspergillosis, itraconazole, 200 mg/day, is probably active, but only if adequate serum concentrations are achieved. New oral and intravenous itraconazole formulations in cyclodextrin may achieve more reliable serum concentrations. No oral drug provides effective prophylaxis against Torulopsis, Fusarium, Trichosporon, or Pseudallescheria. PMID- 1611931 TI - Long-term memory for context-specific category information at six months. AB - The ability of 6-month-old infants to remember a functional category acquired in a specific context was assessed in 3 experiments via an operant procedure in which infants learned to perform a specific action (a footkick) to activate an object suspended before them. In Experiment 1, infants trained with different exemplars in the same context transferred responding to a novel exemplar in the same but not a different context 24 hours later. Experiment 2 revealed that infants' reactivated memory of category training remained intact and context specific after 3 weeks. In Experiment 3, a novel category exemplar was able to reactivate the forgotten memory of category training only in the encoding context. At 6 months, information about the place where categories are constructed is prerequisite for retrieval of a category concept from long-term memory. This requirement insures that early category concepts remain stable over relatively long periods. PMID- 1611932 TI - Infant auditory temporal acuity: gap detection. AB - The development of auditory temporal acuity during infancy was examined in 3-, 6 , and 12-month-old infants and in adults using the gap detection paradigm. Listeners detected a series of gaps, or silent intervals, or variable duration in a broadband noise. In order to vary the acoustic frequencies available to the listener, a high-pass noise was used to mask frequencies above specified cutoffs. High-pass maskers with cutoffs of 500, 2,000, and 8,000 Hz were used. The minimum detectable gap was determined using the Observer-based Psychoacoustic Procedure. The thresholds of 3- and 6-month-olds were considerably poorer than those of the adults, although the effect of masker condition was about the same for these 3 groups. The thresholds of 12-month-olds were significantly worse than the adults when the stimulus was unmasked or when the masker cutoff frequency was 2,000 or 8,000 Hz. When the masker cutoff frequency was 500 Hz, 12-month-olds fell into 2 groups: some had gap thresholds that were about the same as 3- and 6-month-olds, while some had gap thresholds that approached those of adults. In a second experiment, a larger group of 12-month-olds were tested with a 500-Hz masker cutoff. Average performance of 12-month-olds was about the same as that of 3- and 6-month-olds in Experiment 1. Some infants attained thresholds close to those of adults. Thus, gap detection thresholds are quite poor in infants, although the similarity of the effect of frequency on performance in infants and adults suggests that the mechanisms governing temporal resolution in infants operate qualitatively like those in adults. PMID- 1611933 TI - Asymmetric action in the human newborn: sex differences in patterns of organization. AB - We developed a procedure and scale to quantify movement asymmetry in 36 full-term newborns from several normal newborn nurseries (Measure of Behavioral Laterality, MOBL). The majority of newborns had elicited reflexes and spontaneous movements that were stronger and more coordinated on the right than on the left side of the body; there was no asymmetry in the latency, threshold, or habituation of these behaviors. Although asymmetry of different movements was associated if they relied on the same motor pool, there was little association of movement asymmetries among different body regions, indicating that multiple subsystems, rather than a single asymmetric system, controls asymmetric action in the newborn. Finally, there was a sex difference in asymmetry of all 3 distal lower body elicited reflexes: females were right biased, but the majority of males were left biased. These sex differences are discussed in terms of alternative mechanisms for the development of asymmetric action and the role of newborn reflexes in adult voluntary movement. PMID- 1611934 TI - The stressfulness of separation among nine-month-old infants: effects of social context variables and infant temperament. AB - This manuscript reports on the results of 2 experiments dealing with behavioral and adrenocortical responses to separation among 9-month-old human infants. In both experiments the social context of separation was manipulated. The results of Experiment 1 yielded evidence of a statistically significant adrenocortical response to 30 min of separation under conditions in which the substitute caregiver responded sensitivity to infant distress, but was busy and relatively noninteractive when babies were not distressed during the separation period. Altering the behavior of the substitute caregiver such that she was warm, responsive, and interactive throughout the separation produced a significant reduction in adrenocortical activity and in negative affect. In fact, these measures were not significantly different than those obtained when the mother and infant remained together in the playroom (No Separation). In Experiment 2, the effects of group versus singleton care were examined using the less stressful mode of substitute caregiving as described above. No significant condition differences in behavioral distress or cortisol were found. Furthermore, neither condition elicited a significant increase in cortisol over basal levels. Finally, these data provide evidence that maternal reports of infant Distress to Limits temperament, using Rothbart's Infant Behavior Questionnaire, predict adrenocortical responses to separation, while reports of Fear of Novelty do not. PMID- 1611935 TI - The influence of perinatal risk status on contingency learning in six- to thirteen-month-old infants. AB - Learning of a manipulative response was examined in 6-13-month-old well babies and in risk infants who, in the perinatal period, had experienced a range of respiratory interventions (low- and high-risk). 2 contingency conditions (contingent and yoked) were crossed with 2 locations of feedback (local and remote). Both well-baby and low-risk groups reliably discriminated between contingent and noncontingent feedback when it was presented locally, whereas high risk babies failed to make this distinction in the conditioning phase. Risk status reliably predicted the learning performance. No response acquisition was obtained in the remote feedback condition. In extinction, the well-baby and low risk groups decreased their responding, but the high-risk group showed an initial response burst. The findings are discussed in the context of risk-related differences in contingency awareness and frustrative nonreward. Overall, the results confirm that the effects of perinatal compromise involving respiratory complications influence infants' processing of contingency information during the first year of life. PMID- 1611936 TI - Emotion displays in two-year-olds during mishaps. AB - Although it has been shown that toddlers express distress when personal or physical events violate their expectations, there has been little detailed examination of their emotional reactions to such events. In this study, 45 2-year olds were observed during 2 mishaps: a doll breaking and juice spilling. Their emotional reactions and their attempts to fix the mishap were coded. 2 components to their reactions to mishaps were found: one of tension and frustration, and another of concerned reparation. Mishaps elicited more negative emotions in toddlers than free play, and most toddlers attempted to correct the mishap. Children's styles of emotional response to mishaps may be related to maternal mental health. Symptoms of depression and anxiety in mothers were related to a suppression of tension and frustration in their offspring. Maternal acting out symptoms were not related to toddlers' reactions to mishaps. The findings are discussed in terms of the role of emotion in the formation of individual differences in sociomoral functioning and factors contributing to early differences. PMID- 1611937 TI - Inhibition in toddlerhood and the dynamics of the child's interaction with an unfamiliar peer at age five. AB - Measures of inhibition to social and nonsocial unfamiliar events, obtained in toddlerhood, were studied as predictors of social behaviors during an interaction with an unfamiliar peer in 100 5-year-old children. Social inhibition predicted a highly shy and inhibited behavioral pattern with peer and less frequent expression of affect during fantasy play; nonsocial inhibition predicted decreased involvement in group play. Analysis of the changing dynamics of the ongoing peer interaction revealed that the role of child inhibition as a predictor of social behavior may be mostly evident during the initial encounter with the peer. Children who as toddlers were particularly socially inhibited, during the initial phase of peer interaction showed a significantly stronger pattern of shy and inhibited behavior and proximity to mother. In contrast to existing evidence that maternal depression may be a risk factor for the child's long-term peer relationships, no differences in social behavior were found between children of normal and affectively ill mothers during a brief encounter with unfamiliar peers. PMID- 1611938 TI - Talk with your mother or your sibling? Developmental changes in early family conversations about feelings. AB - Developmental changes in the pattern of family conversations and talk about feelings were examined in a longitudinal study of 50 families observed at home when the second-born children were 33 and 47 months old. Significant increases were noted in the total amount of talk and the frequency of talk about feelings between sibling pairs as well as decreases in the amount of mother-child conversation and references to feelings. Differences in whose feelings were discussed and in the context of references to feelings were found for mother child and sibling-child dyads. Developmental changes in the children's use of feeling state language co-occurred with the increase in interaction between children and their siblings. The findings contrast the "complementary" nature of mother-child interaction and the "reciprocal" nature of child-sibling interaction and support the argument that the quality of particular relationships influences the use children make of their communicative competence. PMID- 1611939 TI - Loneliness and peer relations in young children. AB - Recent studies indicate that feelings of loneliness and social dissatisfaction can be reliably assessed with third- through sixth-grade children, and that children who are sociometrically rejected by their peers are significantly more lonely than other children. The present research was designed (a) to examine whether loneliness could be reliably assessed in a population younger than previously studied, (b) to learn whether young children who are poorly accepted by peers report elevated levels of loneliness and social dissatisfaction, (c) to assess whether young children understand the concept of loneliness, and (d) to examine the behavioral characteristics of lonely young children. Kindergarten and first-grade children (N = 440) responded to a questionnaire about feelings of loneliness and social dissatisfaction in school. A subset of children (N = 46) were individually interviewed to assess their understanding of loneliness. To assess sociometric status and behavior, peers were asked to respond to various sociometric measures and behavioral assessment items. Teachers also provided behavioral information about children using a newly developed instrument. Results indicated that nearly all children understood loneliness, that loneliness was reliably assessed in young children, and that poorly accepted children were more lonely than other children. In addition, children who reported the most loneliness were found to differ from others on several behavioral dimensions. PMID- 1611940 TI - Display rules for anger and aggression in school-age children. AB - 2 related studies addressed the development of display rules for anger and the relation between use of display rules for anger and aggressiveness as rated by school peers. Third, fifth, and seventh graders (ages 8.4, 10.9, and 12.8, respectively) gave hypothetical responses to videotaped, anger provoking vignettes. Overall, regardless of how display rules were defined, subjects reported display rules more often with teachers than with peers for both facial expressions and actions. Reported masking of facial expressions of anger increased with age, but only with teachers. Girls reported masking of facial expressions of anger more than boys. There was a trend for aggressive subjects to invoke display rules for anger less than nonaggressive subjects. The phenomenon of display rules for anger is complex and dependent on the way display rules are defined and the age and gender of the subjects. Most of all, whether children say they would behave angrily seems to be determined by the social context for revealing angry feelings; children say they would express anger genuinely much more often with peers than with teachers. PMID- 1611941 TI - Children's beliefs about strategies to reduce parental anger. AB - Age and sex differences in beliefs about strategies for reducing parental anger were assessed. The central question was whether direct intervention strategies are the most effective for, and reflect more advanced understanding of, anger reduction. In Study 1, 120 children ages 4-9 years generated strategies they believed would lessen a parent's anger elicited by 3 situations of increasing complexity. Across ages children proposed direct intervention strategies for the simplest situation, and there was an age increase in suggesting direct intervention strategies for the more complex situations. In Study 2, 180 children, ages 4-12 years, and their parents rated the effectiveness of the strategies generated for the most complex situation (interparental argument). There was no longer a unilinear age increase in believing direct intervention strategies effective. Unlike with older and younger children, there was no agreement between 7-9-year-olds and their parents on the efficacy of direct intervention strategies. PMID- 1611942 TI - Contemporaneous and longitudinal associations of sibling conflict with family relationship assessments and family discussions about sibling problems. AB - The first purpose of this study was to examine contemporaneous and longitudinal associations of maternal and paternal measures of family functioning with observational and self-report assessments of sibling conflict. The second purpose was to determine whether the ways in which families attempt to solve siblings' problems are associated with contemporaneous and longitudinal assessment of sibling conflict. The results indicate that paternal equality of treatment and family harmony during family discussions about sibling problems, as well as parents' perceptions of family cohesiveness, are associated with lower sibling conflict levels. PMID- 1611943 TI - Young children's vulnerability to self-blame and helplessness: relationship to beliefs about goodness. AB - Motivational helplessness, linked to conceptions of intelligence, has been well documented in older children. While some researchers have reported that children just starting school are motivationally invulnerable, others have found evidence of helplessness when these children encounter failure. The present study seeks to determine whether the reactions associated with helplessness can be identified in a new context, that of criticism, and whether any such responses are related to the child's conceptions of goodness. Subjects were 107 5- and 6-year-old children who enacted achievement situations in which teacher criticism was presented. The 39% of children whose own assessments were undermined by criticism exhibited the affect, task choices, and nonconstructive problem-solving strategies characteristic of helplessness. They were also more likely to make global negative self-judgments following criticism, including negative judgments of their goodness. Finally, these children were more likely to endorse stable and global beliefs about goodness. PMID- 1611944 TI - Children's obligatory and discretionary moral judgments. AB - This study examined children's obligatory moral judgments (which reflect a moral requirement) and discretionary moral judgments (which reflect moral worthiness, but not a requirement). 72 children participated across grades 2, 5, and 8 (mean ages, 8-3, 11-0, and 13-11). Children were interviewed in response to stimulus stories that controlled for the degree of agent's cost (low and high) for performing positive moral acts (giving money for food to an impoverished, hungry person) and negative moral acts (not stealing money for food). Results showed that negative moral acts were more often conceived as obligatory than positive moral acts. In addition, the results support the proposition that children's concepts of obligation underlie judgments to codify law, that justice reasoning builds on concepts of welfare, and that with increasing age discretionary moral reasoning incorporates such character traits as benevolence, sacrifice, and supererogation. Discussion includes consideration of how the study's conceptualization and analysis can provide guidance to a moral-developmental research program. PMID- 1611945 TI - Maternal employment and perceptions of young children: Bronfenbrenner et al. revisited. AB - 238 mothers and 116 fathers provided checklist descriptions of their 3-4-year old's behavior; a smaller sample of parents and teachers also assessed the child's behavior 2 years later. There was no evidence of a key finding from a related study by Bronfenbrenner, Alvarez, and Henderson linking part-time employment with more positive maternal perceptions of sons. Indeed, maternal employment (typically, conditioned by mothers' level of education and child gender) was more strongly associated with fathers' and teachers' perceptions of children than with mothers' perceptions, and, in some cases, especially with fathers' and teachers' perceptions of daughters. Fathers perceived their 5-6-year old as having more problem behaviors when mothers were currently employed full time; fathers and teachers viewed children's behavior as more problematic when less-educated mothers had been employed during more years of the child's lifetime. Interpreting these and other findings, we emphasize differences between samples and changes in the ecology of family life. This study underscores the notion that socially "relevant" research is likely to be highly responsive to time and social context. PMID- 1611946 TI - Thresholds of quality: implications for the social development of children in center-based child care. AB - We assessed the quality of center child care relationships with adults and peers for 414 children (ages 14 to 54 months). Classrooms were classified by ratio and group size provisions of the Federal Interagency Day Care Requirements (FIDCR) and by the Early Childhood and Infant and Toddler Environmental Rating Scales. Children cared for in classrooms meeting FIDCR ratios were more likely to be in classrooms rated as good or very good in caregiving and activities. Children in classrooms rated as good or very good in caregiving were more likely to be securely attached to teachers. Securely attached children were more competent with peers. Children cared for in classrooms meeting FIDCR group size were more likely to be in classrooms rated higher in activities. Children in classrooms rated high in activities were likely to orient to both adults and peers. Children with social orientations to adults and peers were more competent with peers. PMID- 1611947 TI - Expertise, aptitude, and strategic remembering. AB - Second- and fourth-grade children were classified according to their knowledge of soccer (experts vs. novices) and IQ (high vs. low), and given 2 sort-recall tasks. One task included items related to the game of soccer and the other included items from familiar natural language categories. Previous research has shown that expertise in a subject can compensate for low levels of performance on text comprehension tasks. Our results, the first examining the effects of both expertise and intelligence on a strategic memory task, were that soccer expert children recalled more items on the soccer list but not on the nonsoccer list than soccer novice children. However, soccer expertise did not modify a significant effect of IQ level, with high-IQ children recalling more than low-IQ children for all contrasts. Interest in soccer was found to be related to expertise but did not contribute to differences in memory performance. The results demonstrate that the knowledge base plays an important role in children's memory, but that domain knowledge cannot fully eliminate the effects of IQ on sort-recall tasks using domain-related materials. That is, although rich domain knowledge seemed to compensate for low aptitude, in that low-aptitude experts performed at the level of high-aptitude novices, its effects were not strong enough to eliminate performance differences between high- and low-aptitude soccer experts. PMID- 1611948 TI - Young children's understanding of the role that sensory experiences play in knowledge acquisition. AB - 3 studies investigated whether young children understand that the acquisition of certain types of knowledge depends on the modality of the sensory experience involved. 3-, 4-, and 5-year-old children were exposed to pairs of objects that either looked the same but felt different, or that felt the same but looked different. In Study 1, 36 children were asked to state, when one of these objects was hidden inside a toy tunnel, whether they would need to see the object or feel it in order to determine its identity. In Study 2, 48 children were asked to state which of 2 puppets knew that an object hidden inside a tunnel possessed a given visual or tactile property, when one puppet was looking at the object and the other was feeling it. In Study 3, 72 children were asked, in a scenario similar to Study 2, to state for each puppet whether he could tell, just by looking or by feeling, that the hidden object possessed a certain visual or tactile property. Children were also asked what was the best way to find out whether a given object possessed a certain visual or tactile property. Results of all 3 studies suggest that an appreciation of the different types of knowledge our senses can provide (i.e., modality-specific knowledge) develops between the ages of 3 and 5. The results are discussed in relation to young children's developing understanding of the role that informational access plays in knowledge acquisition. PMID- 1611950 TI - The Norman Nigro Lectureship. New paradigms of oncogenesis and their implications for surgery in the twenty-first century. PMID- 1611949 TI - Korean children's understanding of multidigit addition and subtraction. AB - This study examined Korean second and third graders' understanding of multidigit addition and subtraction and particularly their ability to explain the trading required when a column sum of the addends is 10 or more. 72 middle-class second- and third-grade children (aged 7-4 to 8-4 and 8-4 to 9-4, respectively, at the time of the midyear interview) attending 2 schools in Seoul, Korea, were asked to solve 2- and 3-digit problems given in vertical form and then were individually interviewed about their conceptual understanding of such problems. Even though the second graders had not yet received instruction in school on 3-digit problems, children in both grades were quite accurate solvers of the multidigit addition and subtraction problems and demonstrated knowledge of the place-value names "ten" and "hundred." Every child also correctly identified the trade between the ones and tens columns as a traded ten. Most of the third graders identified the 1 written in the hundreds column on the addition problems as a hundred, but half of the second graders identified it as a ten. Most of the third graders also gave correct descriptions of the trading (regrouping, borrowing) required by a 3-digit subtraction problem with 2 zeros in the top number. Children used 3 different conceptual structures in discussing the already-solved problems: a multiunit quantities structure, a regular one/ten trades structure, and a combination of these two. These results are compared to the literature on the performance and conceptual structures of children in the United States. PMID- 1611951 TI - Synergistic soft tissue infections of the perineum. AB - Seven patients with necrotizing soft tissue infections of the perineum are described. Predisposing factors related to infection were present in four patients (diabetes mellitus, multiple myeloma, HIV, and a poorly defined immunodeficiency syndrome). Anaerobic and facultative anaerobic bacteria were cultured in each case. Two patients required skin graft closure of the debrided wounds, with the remaining wounds closed by contracture and epithelialization. A diverting sigmoid colostomy to facilitate wound care was performed on one patient who had complete dissolution of all anal sphincters. The role of hyperbaric oxygen therapy in four patients was of uncertain value. PMID- 1611952 TI - Local immunity and metastasis of colorectal carcinoma. AB - The subsets of tumor-infiltrating lymphocytes (TIL) and prostaglandin (PG) E2 were measured in the resected tissues of 32 colorectal cancers without metastasis and 14 with metastasis in order to investigate the local immunity in metastasis of colorectal carcinoma. Subsets of TIL (Leu 1, Leu 2a, Leu 3a, Leu 10, Leu 11b, IL-2 receptor) were detected by immunohistochemical staining of frozen tissues. The number of positive cells was counted and expressed as number positive per 250 x 250 microns 2. The numbers of T cells (Leu 1) and natural killer cells (Leu 11b) were larger in early cancers and decreased in parallel with the presence of metastasis (control [n = 9]: 89 +/- 28, 6 +/- 4; early cancers [n = 9]: 269 +/- 112*, 76 +/- 56*; advanced cancers without metastasis [n = 11]: 182 +/- 80*, 56 +/- 59*; advanced cancers with metastasis [n = 11]: 76 +/- 42*, 26 +/- 21; values are mean +/- SD; * P less than 0.05, ANOVA). The level of PG E2 from the draining vein (V) measured by radioimmunoassay was higher than that from the feeding artery (A) (119.1 +/- 14.3 vs. 15.4 +/- 1.9 pg/ml; P less than 0.001). The PG E2 V/A ratio of cancers with metastasis was significantly higher than that of those without metastasis (13.2 +/- 2.4 vs. 5.6 +/- 0.8; P less than 0.001). TIL was decreased in parallel with the increase of PG E2 V/A ratio. We conclude that TIL and PG E2 may play an important role in metastasis of colorectal carcinoma and that PG E2 has an adverse effect in suppressing local immunity and enhancing metastasis. PMID- 1611953 TI - Clinical index to quantitate symptoms of perianal Crohn's disease. AB - We describe an anal disease activity index suitable for use in prospective studies of treatment and recording the natural history of anal disease. We studied 40 patients with perianal Crohn's disease (PACD), 14 patients with anal disease not related to Crohn's disease, and 10 normal individuals. Seven symptoms related to anal disease were measured using a linear analog scoring system, which proved easy for the patients to complete. Only three of the seven clinical parameters studied before and after treatment had a high discriminant value. On the basis of these findings, we conclude that a good index of response to therapy in patients with anal disease can be obtained from a linear analog scoring of three symptoms: spontaneous anal pain, pain following defecation, and inhibition of locomotion by pain. The index should be of value in comparing management options in PACD. PMID- 1611954 TI - Ileostomy output of gas and feces before and after conversion from conventional to reservoir ileostomy. AB - In 28 patients who had previously had a proctocolectomy for ulcerative colitis, the ileostomy output of feces was determined before and after conversion to continent reservoir ileostomy, as was the output of gas in 20 of the patients. The median output of feces/24 hours collected in the hospital was 576 g before and 692 g after conversion (P less than 0.05); when collected at home the corresponding figures were 734 g and 740 g, respectively. In the majority of patients, the change in fecal ileostomy output after the conversion was not considerable, while in a few patients there was a marked increase. The fecal output was 24 percent (P less than 0.01) and 11 percent (P less than 0.01) larger at home than in hospital before and after conversion, respectively. The proportion dry weight of ileostomy discharge decreased after conversion (P less than 0.01). The median gas volume in the ileostomy output/24 hours was 1,664 ml before and 1,450 ml after conversion. The gas constituted 58 percent of the output and is significant with respect to the required reservoir capacity. Recording the emptying volumes and frequency in patients with reservoir ileostomy showed that, in general, patients with large output expand their reservoir capacity instead of increasing their emptying frequency. PMID- 1611955 TI - Biopathologic characteristics of DNA content in crypt cells of transitional mucosa adjacent to carcinomas of the rectum and rectosigmoid. AB - The transitional mucosa (TM) adjacent to carcinomas of the large bowel shows histologic and mucin histochemical changes that may indicate premalignant change and may be of prognostic value after radical resection. In this study, 10 anterior resection specimens from patients with carcinomas of the rectum and rectosigmoid were used to compare the nuclear DNA content in TM with those in cancer tissue and with those in nontransitional mucosa (N-TM; i.e., uninvolved mucosa remote from tumors showing normal histologic and mucin histochemical features). The nuclear DNA content was assessed using DNA image cytometry on Feulgen-stained sections. As compared with N-TM, crypts in TM contained greater numbers of cells, were elongated, and were more likely to be branched with marked sialomucin secretion, accompanied by a marked reduction in the normal sulfomucin content. The mean nuclear DNA content in the upper, middle, and lower thirds of crypts was significantly higher in TM than in N-TM, and the nuclear DNA content in TM exhibited no correlation to that in tumors. The results suggest that TM adjacent to carcinomas of the rectum and rectosigmoid has higher proliferative activity, providing further evidence that TM may be an unstable premalignant change. PMID- 1611957 TI - Restorative proctocolectomy in patients after previous intestinal or anal surgery. AB - Restorative proctocolectomy is now established as the procedure of choice in many patients with ulcerative colitis or familial polyposis coli as well as in some patients with multiple colorectal tumors, ischemia, trauma, or congenital abnormalities. Some patients, however, may have had previous pelvic, abdominal, or perineal surgery, which might be considered a contraindication to restorative proctocolectomy. In a consecutive series of 73 private patients undergoing restorative proctocolectomy under one surgeon, we have reviewed in detail 13 who had had previous "significant" abdominal, pelvic, or anal surgery. Eight patients had previously had surgery for fistula-in-ano or fissure-in-ano, two had had an anal sphincter repair, and three had undergone possibly compromising abdominal or pelvic surgery prior to restorative proctocolectomy. Twelve of the 13 made an uncomplicated recovery from restorative proctocolectomy, although one has since died from carcinomatosis. One patient died after closure of an ileostomy from a combination of enterocutaneous fistula, infection, bleeding, and a perforated duodenal ulcer. One patient developed sepsis, necessitating removal of the pouch, and is classified as a failure. Two of the remaining 11 have had minor long-term functional problems with nocturnal fecal incontinence, and one patient needs to catheterize the pouch to evacuate, but all three patients prefer a pouch to an ileostomy. Restorative proctocolectomy can be performed successfully even after previous pelvic, abdominal, or anal surgery with an acceptable complication rate when compared with pouch surgery in the uncompromised patient. PMID- 1611956 TI - Prevalence of colorectal polyps in Filipinos. An autopsy study. AB - From May 1988 to May 1990, a prospective autopsy study was performed in patients who died at the Philippine General Hospital in Manila, Philippines. Patients younger than 10 years of age, patients with a history of large bowel resection, and patients whose deaths were related to trauma were excluded. There were 416 patients; 246 were males, and 170 were females. The mean age was 47 years (range, 11-95 years). Six of the 416 patients (1.4 percent) were found to have polyps. One patient had an inflammatory polyp, one was diagnosed with familial adenomatous polyposis, and one had an associated cecal carcinoma. Five "sporadic" adenomatous polyps were found in the remaining three patients (prevalence rate, 0.7 percent). All of the adenomatous polyps were located distal to the hepatic flexure and exhibited only mild atypia. The mean size was 6.4 mm (range, 2-20 mm). The incidence of colorectal adenomas in Filipinos is low compared with that in age-adjusted Western populations. This finding coincides with a low incidence of colorectal carcinoma. The documentation of a low risk for adenomatous polyps and colorectal cancer indicates that it would be difficult for massive screening programs to demonstrate a significant positive impact on the early detection of colorectal neoplasias in the Filipino general population. PMID- 1611958 TI - Microcarcinoids and diversion colitis in a colon defunctioned for 18 years. Report of a case. AB - Submucosal microcarcinoids are described in association with diversion colitis in a colon defunctioned for 18 years. Coexistent florid neuronal hyperplasia is postulated as a cause of microcarcinoid formation. PMID- 1611959 TI - Use of the de Pezzer catheter to facilitate endoanal pull-through during ileal pouch-anal anastomosis. AB - Ileal pouch-anal anastomosis is now the treatment of choice for selected patients requiring proctocolectomy for benign mucosal disease of the large intestine. Pelvic sepsis continues to be a major postoperative complication. This is often subsequent to the technical complexity of the intestinal pull-through and ileal pouch-anal anastomosis. We report the use of the de Pezzer catheter to facilitate this often difficult reservoir pull-through during restorative proctocolectomy. This is an inexpensive and simple aid which has consistently helped to decrease operative difficulty, especially where pelvic access is restricted. By enabling the avoidance of clamps and tissue forceps, it has reduced the incidence of contamination and tissue trauma. It has enabled pull-through without undue tension on the reservoir and has facilitated postoperative drainage of the reservoir. PMID- 1611960 TI - Experience with the use of the circular stapler in rectal surgery. AB - This report provides our personal experience along with a general overview of the use of the circular stapler in rectal surgery. To determine the results of our experience with the use of the circular stapler for construction of anastomoses following resection, a series of 215 anastomoses performed in 214 patients was reviewed. The patients ranged in age from 33 to 88 years. There were 116 men and 98 women. Indications for operation included malignancy, diverticular disease, villous adenoma, Crohn's disease, and rectal procidentia. The types of operation performed included removal of varying portions of the large bowel. The anastomosis was performed in a uniform manner with the EEA (United States Surgical Corp., Norwalk, CT) and more recently the CEEA (United States Surgical Corp., Norwalk, CT). The operative mortality was 0.47 percent, with the death being unrelated to the anastomosis. Intraoperative complications encountered included bleeding, difficult extraction, instrument failure, incomplete doughnuts, deficient anastomoses, and miscellaneous problems. Early postoperative complications included one leak and a number of complications unrelated to the anastomoses. Anastomotic stenosis developed in 27 patients, but only 8 were permanent and only 3 of these were symptomatic. Two of these patients were treated with balloon dilatation. Anastomotic recurrences developed in 13.1 percent of patients. Our experience gained with the circular stapling device and that reported in the literature have shown it to be a reliable method of performing anastomoses to the rectum in a safe and expeditious manner. PMID- 1611961 TI - Starting oral contraceptives--which, when and how? AB - About one quarter of women in Britain aged 18-44 use oral contraceptives, and almost half of those aged 20-29. Many will use more than one type during their years of sexual activity. Changes will occur as new products are introduced and new risks identified or in response to unwanted effects. Decisions may also be prompted by the need to restart oral contraception after a break as part of planned parenthood. Oral contraception is chosen chiefly because it is reliable and does not interrupt spontaneous sexual activity. Whether a combined oral contraceptive pill (COC) or a progestagen-only pill (POP) would be the more appropriate depends mainly on the woman's medical history, smoking habits and age. Most women will want good cycle control, and a few will prefer to take an inactive pill for a few days in each cycle rather than have a pill-free interval. This article discusses the choice when starting, restarting or switching oral contraception. PMID- 1611962 TI - [Administration of infusions by patient care personnel]. PMID- 1611963 TI - [Complications after bone marrow biopsy]. PMID- 1611964 TI - [HIV transmission by the communion chalice?]. PMID- 1611965 TI - [Exercise performance after long-term administration of enalapril or metoprolol. A randomized double-blind study of hypertensive leisure-time sportsmen]. AB - A randomized double-blind trial was conducted in 36 leisure-time sportsmen (mean age 40.1 +/- 5.4 years) with mild or moderate essential hypertension (WHO groups I or II) to find out whether an 8-week antihypertensive treatment with daily 10 20 mg enalapril or 100-200 mg metoprolol changed their exercise performance. This was measured by bicycle spiroergometry together with determination of lactate levels, before and at the end of the treatment period. Maximal oxygen uptake rose by 1.86 ml/kg.min during enalapril administration and by 1.06 ml/kg.min at the individual anaerobic threshold. But under metoprolol these parameters fell by 6.57 ml/kg.min and 4.61 ml/kg.min, respectively. After treatment with these two drugs 3 and 15 patients, respectively, had the sensation of greater exercise performance at identical exercise levels. The differences in exercise between the two drugs using the stated three primary criteria were statistically significant. The Watt-time product decreased in only one of the patients of the enalapril group, but in 17 of the metoprolol group. Only metoprolol significantly reduced exercise heart rate. Both drugs caused a similar fall in systolic blood pressure during exercise. PMID- 1611966 TI - [Giant-cell arteritis limited to the femoral arteries]. AB - A previously healthy 48-year-old woman developed, over several months, increasing pain in her hips, cervical and lumbar spine as well as the shoulders. In addition she developed intermittent claudication after walking 100-200 m. Erythrocyte sedimentation rate (ESR) was 35-43 mm in the first hour; the IgM concentration was raised to 610 mg/dl. Angiography demonstrated symmetrical occlusion of both superficial femoral arteries. An attempt at thrombolysis having failed, a biopsy of the femoral artery wall was obtained. This revealed a florid arteritis, in part as giant-cell arteritis with destruction of the elastic structures, while the adjacent muscle was unchanged. Subsequent biopsy of the temporal artery was normal. Treatment consisted at first of 60 mg prednisolone and 100 mg aspirin, both daily for 4 weeks. The ESR fell and the free-of-pain walking distance rose. There has been no recurrence of pain after stepwise reduction over one year of the steroid dosage until its discontinuation. PMID- 1611967 TI - [Fasciola hepatic infection in a family: diagnosis and therapy]. AB - A 39-year-old man was hospitalized because of a 5-week history of feeling very ill, with fever up to 39 degrees C and nonspecific upper abdominal pain. He looked very pale and his spleen was painful on palpation. There was a blood eosinophilia of over 50% and computed tomography demonstrated hypodense areas in the liver, suggesting a parasitic infection with liver involvement. An ELISA factor of over 100 and the finding of liver fluke eggs in bile confirmed the diagnosis of Fasciola hepatica infection, which was probably acquired by eating wild watercress when visiting in the Allgau. A fasciola infection was also proven in his 37-year-old sister who for some time had complained of colicky right-sided upper abdominal pain, her 40-year-old husband with similar symptoms and their 10 year-old daughter. All four were successfully treated for two days with 10 mg/kg triclabendazole daily by mouth. Persons eating raw vegetables and salads of wild growing plants are at risk of being infected with Fasciola hepatica. PMID- 1611968 TI - [Paroxysmal nocturnal hemoglobinuria. Diagnosis by fluorescence-activated cell analysis]. PMID- 1611969 TI - [Androgens and bone metabolism. Significance in osteoporosis in man and woman]. PMID- 1611970 TI - [Helicobacter pylori: from harmless commensal to clinically significant disease factor]. PMID- 1611971 TI - [Clinical results and material behavior of composite, ceramic and gold inlays]. AB - Laboratory-manufactured gold, ceramic and composite inlays were compared with the CAD/CAM produced CEREC inlay experimentally and clinically. The following systems were examined: Dicor, Optec, Hi-Ceram, Du-Ceram, Cerec, Kulzer, Coltene, SR Isosit composite inlays, and gold inlays (Degulor C) with adhesive fixation (group I) and with zinc oxide phosphate cement (group II). In the clinical trial inlays in 270 teeth were re-evaluated in a total of 73 patients after 2.3 to 5 years. After 3 years the results obtained with Optec, Hi-Ceram and the Coltene composite inlay were less favorable than those of other systems--statistically however, this difference was of rather low significance (p less than 0.05). Fractures of ceramic inlays occurred in 6 cases within 8 months. 10 failures of ceramic and composite inlays were due to secondary caries. PMID- 1611972 TI - [Marginal adaptation of adhesive inlays after removal of unpolymerized composite cement]. AB - The removal of polymerized excess resin cement around adhesive inlays is very time consuming and often tooth-destructive. In this study we evaluated, if brushing away of the unset resin cement produced any marginal imperfections. It was found that this procedure caused underfilled margins especially in the occlusal portion of the inlay margins. For this reason the use of this method to remove excess resin cement is not recommended. PMID- 1611973 TI - [592 pulp cappings in a dental office--a clinical study (1966-1990)]. AB - In a dental office 592 direct and indirect pulp cappings were followed up to 24 years. 404 of these pulps remained vital. The success of this treatment seemed to be related to age, type of tooth, and the extent of pulp exposure. In some advanced cases the clinical outcome was better than expected. PMID- 1611975 TI - [10 years of outpatient dental surgery using endotracheal anesthesia. Research report from dental practice]. AB - For certain groups of patients, e.g. handicapped people, children or extremely anxious adults, dental surgery with local anesthesia is not possible and hospitalisation is not desirable. In order to provide outpatient treatment using endotracheal anesthesia, a successful practice-oriented concept is presented, involving cooperation between the dental surgeon and an anesthetist in private practices. In the past 10 years, 4205 patients have received outpatient treatment according to this concept. PMID- 1611974 TI - [Nerve injuries following nerve blocking in the pterygomandibular space]. AB - In a prospective study 506 patients with nerve blocks in the pterygomandibular space were examined before and 3-7 days after local anaesthesia. Clinical neurosensory testing including two-point discrimination revealed no differences between the neurological status before and after injection. Between December 1987 and April 1991 8 patients with 9 nerve injuries (lingual nerve n = 8, inferior alveolar nerve n = 1) after nerve blocks in the pterygomandibular space were treated. In addition to hypaesthesia or anaesthesia 5 out of 8 patients with injection damages of the lingual nerve suffered from a loss of taste sensations. Only 2 of the total of 9 nerve lesions showed a complete recovery of the neurological deficit. One patient with a persistent pain syndrome of the lingual nerve after an injection damage underwent partial nerve resection and microsurgical reconstruction after intraoperative monitoring of somatosensitive evoced-potentials. The operation was successful for only a few weeks, afterwards a relapse of the pain syndrome took place. PMID- 1611976 TI - [Prerequisites for outpatient treatment using general anesthesia]. AB - The possibility of profound preoperative examination by an experienced anesthesiologist, the cooperation of dentists, oral and maxillo-facial surgeons, anesthesiologists, pediatricians, internal specialists and family doctors, careful planning, conduction and supervision of anesthesia and postoperative treatment in a recovery room are essential in safe outpatient treatment under general anesthesia in the field of oral and maxillo-facial surgery. In case of unexpected postoperative complications patients have to be hospitalized. All the aforementioned requirements in respect of staff, apparatus and rooms must be fulfilled. PMID- 1611977 TI - [Nasal intubation for frontobasal fractures?]. AB - In most cases the surgical management of craniofacial fractures involves a correction of the occlusion. This requires nasal intubation. In a frontobasal fracture with simultaneous CSF fistula, nasal intubation is thought to increase the risk of meningitis. An analysis of the records of 160 patients with frontobasal fractures and CSF fistulae revealed that the route of intubation had no influence on the post-operative complication rate. Nasal intubation is therefore not contraindicated in frontobasal fractures with CSF fistulae. PMID- 1611978 TI - [Fiberoptic intubation as a safe method for the treatment of odontogenic abscesses]. AB - Infections caused by dental disease may result in severe swelling of the throat and whole neck. In an operation for opening an abscess, the initial phase of general anaesthesia is often critical due to obstructions of the airway and trismus. Therefore the wide use of a fibre-optic intubation is advocated in order to avoid an emergency tracheostomy or other complications. PMID- 1611979 TI - [Clinical studies on the influence of Ornipressin (POR 8) on the cardiovascular system in general anesthesia]. AB - A clinical prospective study of 231 patients was conducted to examine the influence of Ornipressin (POR 8) on the cardiovascular system. The standard concentration of the vasoconstrictor was 0.2 i.u./ml. A control group of 34 patients received 0.9% NaCl solution. In less than 10% of all cases blood pressure or pulse frequency changed up to 30 mmHg or 30 bp. m. Cardiac arrhythmias without clinical relevance could be observed sporadically. There were significant differences to the control group only in terms of pulse rate under volatile anaesthetics, and changes in blood pressure during the first 10 minutes under neurolept analgesia and under combined anaesthesia. PMID- 1611980 TI - [Anxiolysis vs. intravenous conscious sedation during maxillary fracture splinting in local anesthesia]. AB - For the conservative treatment of mandibular fractures with arch bars under local anaesthesia we used two forms of premedication in 140 patients: 1. an analgetic sedation with pethidine 1 mg/kg body weight and promethazine 0.5 mg/kg body weight i.m. (n = 70 cases) 2. an anxiolytic sedation with midazolam 0.05-0.1 mg/kg body weight i.v. (n = 70 cases). The effect of the premedication was measured retrospectively by the mean amount of local anaesthetics used during splinting. It could be noted that the mean consumption of local anaesthetics was significantly lower in the midazolam-group than in the pethidine/promethazine group. The postoperative subjective assessment of the operation by the patients is better under anxiolytic than under analgetic sedation, too. PMID- 1611981 TI - [Preoperative blood alcohol levels in patients hospitalized for prolonged surgical procedures]. AB - Self medication using anxiolytic and relaxing agents prior to surgery is a common phenomen in many patients. In our prospective study of 356 patients undergoing prolonged surgical procedures (greater than 3 h), we evaluated the preoperative ethanol level of the blood using gas-chromatography. In 39 (10.9%) of 307 tumor patients ethanol could be detected in high concentrations, indicating the ingestion of disinfectants. Among our 49 orthognathic cases blood alcohol was found in 4 cases (8.2%). Since the minimum effective dose for ethanol ist 0.1 to 0.2 g/l, the patients' legal capacity when giving informed consent for surgery and anesthesia is to be questioned and the risks of analgosedation in outpatient must be considered. PMID- 1611982 TI - [Prophylaxis of alcohol withdrawal syndrome in prolonged oral and maxillofacial surgery procedures]. AB - Alcohol-addicted patients have a high risk of intercurrent complications during the postoperative period. In addition to the predisposition for infection, alcohol withdrawal syndrome is potentially life-threatening in these patients. However, this concerns only addicts, and definite preoperative diagnosis of addiction therefore is a crucial parameter in assessing the postoperative risks. In our department, 40% of maxillofacial tumor patients with a history of alcohol abuse were assessed as alcohol-addicted according to a complex diagnosis scheme. In these patients, postoperative withdrawal syndrome prophylaxis with continuous, low-dose alcohol infusion is indicated after exclusion of contraindications. If prophylaxis is impossible and differential diagnosis has confirmed a withdrawal syndrome, therapy must take into account the patient's symptoms and the latest neurobiochemical findings on withdrawal-related imbalances in neuronal transmitter systems. PMID- 1611983 TI - [Does the use of sympathicolytics to prevent withdrawal syndromes compromise microvascular anastomoses?]. AB - Since 1986 we have been using Clonidine in patients with alcoholic history as a prophylaxis to avoid postoperative delirious states. This therapy does not compromise microsurgical vascular anastomoses. PMID- 1611984 TI - [Differential indication of tracheotomy in oral and maxillofacial surgery]. AB - In the hospital for Oral and Maxillofacial Surgery at the Medical University Hannover 105 tracheostomies were performed between 1980 and 1990. We see a limited indication for a general prophylactic tracheotomy in patients with ablative surgery and microvascular reconstructive procedures. The indication for tracheotomy must be considered in each individual case. PMID- 1611985 TI - [Comparison of two methods for conscious sedation in maxillofacial surgery with local anesthesia]. AB - A randomised, prospective study was conducted to compare the efficiency and safety of methods for intravenous conscious sedation in patients undergoing oral surgery under local analgesia. 150 systemically healthy patients (ASA Class I and II) participated. Three groups were formed: group 1 received 0.05 mg/kg midazolam; group 2 0.05 mg/kg midazolam, 1.5 mg/kg tramadol, 50 mg alizaprid; group 3 0.05 mg/kg midazolam, 0.2 mg/kg nalbuphine, 50 mg alizaprid. Blood pressure, heart rate and oxygen saturation were measured throughout the procedure. The results confirmed that the use of nalbuphine (group 3) allows a reduction in the mean dosage of midazolam required to produce satisfactory sedation and effected a more rapid recovery time compared to group 12 and 2. With the combination nalbuphine and alizaprid nausea and vomiting could be reduced for the most part compared to group 2. PMID- 1611986 TI - [The question of oral sedation using midazolam in outpatient dental surgery]. AB - The aim of the present study was to evaluate the effect of one tablet of midazolam (Dormicum 7.5 mg) used as a premedicant for minor oral surgery and to assess the potential risk of hypoventilation. In all of the patients no significant drop in arterial oxygen saturation could be observed, but on the other hand, no real anxiolytic or amnestic effects either. With the little therapeutic use observed with the given premedication, a more widespread application of the substance in this dosage cannot be recommended, particularly when taking into account the possibility of complications and the loss of the patients's fitness to drive for the next twelve hours. PMID- 1611987 TI - Remembrance: Mort and Griff. PMID- 1611988 TI - Effect of dietary calcium or phosphorus restriction and 1,25-dihydroxyvitamin D administration on rat intestinal 24-hydroxylase. AB - 1,25-Dihydroxyvitamin D-24-hydroxylase (24-hydroxylase) modulates the biological effects of 1,25-dihydroxyvitamin D [1,25-(OH)2D] in tissues. The presence of 24 hydroxylase in intestinal mucosa and the mass of the intestine suggest that the intestine is a major site of catabolism of 1,25-(OH)2D. How intestinal levels of 24-hydroxylase are regulated under various dietary conditions, such as calcium (Ca) or phosphorus (P) restriction, is poorly understood. In a series of trials on weanling and mature rats, the effects of dietary Ca or P restriction were compared with the effects of exogenous 1,25-(OH)2D3 administration on intestinal 24-hydroxylase activity. Exogenous administration of 1,25-(OH)2D3, by single bolus injection or constant infusion, increased intestinal 24-hydroxylase activity significantly. Dietary Ca and P restriction both resulted in increased plasma 1,25-(OH)2D3 concentrations several-fold above control rat values (P less than 0.001) and to levels higher than those achieved by constant infusion of 1.3 ng 1,25-(OH)2D3/h. Dietary Ca restriction increased intestinal 24-hydroxylase 6- to 20-fold above that of rats fed a Ca-replete diet (P less than 0.001). Dietary P restriction had no significant effect on intestinal 24-hydroxylase activity. These data suggest that dietary Ca restriction results in increased plasma levels of 1,25-(OH)2D3, which, in turn, leads to up-regulation of intestinal 24 hydroxylase. Conversely, dietary P restriction prevents 1,25-(OH)2D3-mediated up regulation of 24-hydroxylase. PMID- 1611989 TI - Differential effects of glucocorticoid on recruitment and activity of osteoclasts induced by normal and osteocalcin-deficient bone implanted in rats. AB - Prolonged glucocorticoid excess is associated with bone loss. Among the contributory factors are glucocorticoids' suppression of bone formation and stimulation of bone resorption. In this study, the effects of glucocorticoids on bone resorption were evaluated in a rodent model. Subcutaneous implants of devitalized mineralized bone particles (BPs) elicit the recruitment of progenitor cells and their differentiation to osteoclasts which resorb the BPs. The effects of glucocorticoids on both the recruitment and the activity of cells induced by normal BPs were distinguished based upon when treatment was initiated. When treatment with hydrocortisone or dexamethasone was initiated at the time of BP implantation, the recruitment of bone-resorbing cells was impaired and a subsequent decrease in BP resorption was found. On the other hand, when treatment was initiated on day 7, glucocorticoids increased osteoclastic resorption and tartrate-resistant acid phosphatase activity. We also tested hydrocortisone's effect to stimulate the activity of cells associated with osteocalcin-deficient BPs. As previously reported, BPs deficient in osteocalcin were poorly resorbed as a result of decreased formation and activity of osteoclasts. Hydrocortisone had an even more pronounced effect in stimulating the low level resorption of the osteocalcin-deficient BP implants than of the normal BP implants. These findings show differential effects of glucocorticoids on two aspects of bone resorption: they inhibit the recruitment and/or differentiation of bone-resorbing cells, but they stimulate the activity of existing osteoclastic cells. The ability of glucocorticoids to increase resorption of normal bone and to overcome resistance to resorption of osteocalcin-deficient bone suggests an important regulatory effect of glucocorticoids in the activation of osteoclasts to increase bone resorption. PMID- 1611990 TI - Effects of etidronate-mediated suppression of bone remodeling on aluminum-induced de novo bone formation. AB - The mechanism by which aluminum chloride stimulates de novo bone formation is unknown. To evaluate the role of bone remodeling and mature osteoblastic function in aluminum-induced neoosteogenesis, we compared the osteogenic effects of aluminum in normal beagles to those in animals with low turnover osteomalacia induced by treatment with etidronate [1-hydroxyethane-1,1-diphosphoric acid (HEBP)]. As assessed by quantitative bone histomorphology, beagles treated with HEBP developed low turnover osteomalacia characterized by a 78% reduction in osteoblast number, a 5.5-fold increase in osteoid volume, complete absence of active mineralization, and diminished resorption surfaces compared to untreated controls. The iv administration of aluminum chloride to normal dogs generated new trabecular structures in the marrow cavity consistent with induction of de novo bone formation. This response consisted of increased trabecular bone volume and number, accumulation of woven osteoid, and increased number of bone-forming cells. The concomitant administration of HEBP failed to prevent induction of de novo bone formation by aluminum. Instead, the neoosteogenic process was superimposed on low turnover osteomalacia in HEBP-treated dogs. Serum aluminum concentrations were increased 2-fold, whereas bone aluminum accumulation was reduced by 58% in HEBP- and aluminum-treated dogs compared to that in aluminum treated controls. These findings indicate that aluminum stimulation of neoosteogenesis in beagles is independent of mature osteoblast function, normal bone remodeling, and total bone aluminum accumulation. Rather, aluminum-induced de novo bone formation appears to result from stimulation of mesenchymal precursors to form a primitive type of bone which is distinct from coupled bone formation. PMID- 1611991 TI - Adenosine triphosphate-sensitive K+ channels may not be the sole regulators of glucose-induced electrical activity in pancreatic B-cells. AB - Stimulation of insulin release by glucose requires Ca2+ influx in pancreatic B cells. This influx occurs during phases of electrical activity (slow waves of membrane potential with superimposed spikes) that can be monitored with intracellular microelectrodes. It has been suggested that closure of ATP sensitive K+ channels contributes to the increase in electrical activity (and, hence, in Ca2+ influx and insulin release) produced by suprathreshold (greater than 7 mM) concentrations of glucose. If this is the sole mechanism of control, the decrease in electrical activity that follows a decrease in glucose concentration should be mimicked by opening these ATP-sensitive K+ channels. This was achieved by diazoxide, which selectively and directly acts at the channel level (without decreasing B-cell metabolism), and azide, which indirectly opens the channels by inhibiting mitochondrial ATP production. Stepwise lowering of the glucose concentration from 15 to 8 mM progressively decreased electrical activity in B-cells. This decrease was characterized by a shortening of the slow waves and a lengthening of the intervals between the slow waves, with little change in slow wave frequency. Similar changes followed the addition of azide (250-750 microM) to a medium containing 15 mM glucose. In contrast, in the presence of 15 mM glucose, diazoxide (5-20 microM) considerably increased the interval duration, but did not shorten the slow waves, thus causing a marked fall in slow wave frequency. In B-cells persistently depolarized by 30 mM glucose, diazoxide restored slow waves and intervals that were much longer than those recorded when the same cells were stimulated by 15 mM glucose. In conclusion, decreasing mitochondrial ATP production with azide is more able to reproduce the effects of a decrease in glucose concentration on electrical activity in B-cells than a direct pharmacological opening of ATP-sensitive K+ channels with diazoxide. This suggests that ionic channels other than ATP-sensitive K+ channels are under metabolic control and may contribute to the regulation of electrical activity by glucose. PMID- 1611992 TI - Identification and developmental regulation of cadherin messenger ribonucleic acids in the rat testis. AB - Cellular interactions in the rat testis are suggested by the presence of gap junctions between developing germ cells and Sertoli cells as well as tight junctions between adjacent Sertoli cells. Cadherins are cell surface proteins that mediate calcium-dependent intercellular adhesion. In these experiments the presence and developmental regulation of three cadherins have been examined: epithelial cadherin (E-Cad), neural cadherin (N-Cad), and placental cadherin (P Cad). Northern blot analysis of testicular RNA indicates the presence of N-Cad [4.3 and 3.5 kilobases (kb)] and P-Cad (3.5 kb) transcripts. No E-Cad message was detected. To determine whether mRNA concentrations for P-Cad and N-Cad are regulated during postnatal rat testicular development, testes from rats ranging in age from 7-91 days were subjected to Northern blot analysis. Relative P-Cad mRNA levels were highest at 7 days of age and decreased to almost half of these levels by day 14. P-Cad mRNA levels subsequently decreased to low levels and remained constant thereafter. This contrasted with the developmental pattern observed for the 4.3-kb N-Cad transcript, which was low early in testicular development but increased to peak levels on day 42, coincident with the shedding of the first sperm. N-Cad mRNA concentrations decreased from 42 to 56 days and then remained constant until 91 days. While mouse P-Cad antibody did not cross react with rat P-Cad, immunoblots of testicular membrane protein preparations identified the presence of immunoreactive N-Cad protein in the testis. The presence of N-Cad protein confirms that N-Cad mRNA is translated in this tissue. The developmental patterns of P-Cad and N-Cad mRNA suggest a role for P-Cad early in testicular development, while N-Cad appears to play a role in later stages of spermatogenesis. PMID- 1611993 TI - Detection of interleukin-1, interleukin-6, and tumor necrosis factor-alpha in the uterus during the second half of pregnancy in the mouse. AB - This study demonstrated interleukin-1 (IL-1), IL-6, and tumor necrosis factor alpha (TNF alpha) in the mouse uterus during the second half of pregnancy (days 9 18). High concentrations of IL-1 alpha mRNA and bioactive IL-1 were detected between days 12-17. IL-1 bioactivity decreased to very low levels as pregnancy approached parturition. IL-6 mRNA was detected from days 9-18, and IL-6 bioactivity approximately paralleled IL-1 bioactivity. High levels of IL-1 and IL 6 bioactivity, but not IL-1 or IL-6 mRNA, were detected in the placenta between days 12-17. Placental IL-1 and IL-6 also decreased to low levels near parturition. TNF alpha was expressed from days 9-17, and a peak of TNF alpha bioactivity was detected during the period immediately before parturition. TNF alpha mRNA and TNF alpha bioactivity were not detected in the placenta. On day 18, the day of parturition, the concentrations of IL-1, IL-6, and TNF alpha mRNA were very low relative to those on other pregnancy days. Immunocytochemistry with antibodies to IL-1, IL-6, and TNF alpha was used to confirm the presence of all three cytokines in uterine cells throughout the second half of pregnancy. Those data showing the kinetics of cytokine production during fetal development raise the possibility that cytokines and cytokine-induced mediators modulate cellular events during the late stages of pregnancy in the mouse. PMID- 1611994 TI - Glucose- and acetylcholine-induced increase in intracellular free Ca2+ in subpopulations of individual rat pancreatic beta-cells. AB - The effects of glucose and acetylcholine (ACh) on the intracellular free Ca2+ ion concentration ([Ca2+]i) were measured using fura-2 microspectrofluorimetry in individual rat pancreatic beta-cells prepared by enzymatic digestion and fluorescence-activated cell sorting. The average [Ca2+]i was 139 +/- 2.2 nM (n = 84) in the presence of 4.4 mM glucose. At 17.8 mM, glucose caused transient or sustained increases in [Ca2+]i in some individual beta-cells (15% of the total cells tested). However, the majority of glucose (17.8 mM)-nonresponsive cells responded to ACh, cholecystokinin-8, and K+. ACh at 10(-4) M stimulated increases in [Ca2+]i in most of the glucose-nonresponsive beta-cells in the presence of 4.4 mM glucose, and the effect was concentration dependent. High concentrations of glucose potentiated ACh-induced increases in [Ca2+]i observed in some of the glucose-nonresponsive beta-cells (glucose-sensitive cells), demonstrating that the function of some beta-cells is affected by the interaction of glucose with ACh. However, glucose did not affect the ACh-induced increase in [Ca2+]i in other glucose-nonresponsive cells (glucose-insensitive cells). These data strongly indicate that there are populations of beta-cells that exhibit different [Ca2+]i responses to glucose. PMID- 1611995 TI - Vasopressin mediates the interleukin-1 alpha-induced decrease in luteinizing hormone secretion in the ovariectomized rhesus monkey. AB - Arginine vasopressin (AVP) has previously been shown to participate in the neuroendocrine control of the adrenal axis. In this study we investigated the role of AVP in the mechanisms linking stress and decreased gonadotropin secretion and evaluated the action of an AVP antagonist on interleukin-1 alpha (IL-1 alpha) induced changes in gonadotropin and cortisol release in the primate. Adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of IL-1 alpha (2.1 micrograms/30 min; n = 5) or IL-1 alpha plus an AVP antagonist (240 micrograms/120 min; [deamino-Pen1,O-Me-Tyr2,Arg8] vasopressin; n = 7); the AVP antagonist infusion was started 30 min before IL-1 alpha and continued for 2 h. Controls included intracerebroventricular infusions of physiological saline (n = 5) or AVP antagonist alone (n = 3). LH concentrations were measured at 15-min intervals during a 3-h preinfusion morning baseline control period and a 5-h postinfusion period. Cortisol concentrations were determined at 45-min intervals. Pulsatile LH release remained unchanged after a control saline or AVP antagonist infusion. Overall LH concentrations decreased significantly after IL-1 alpha infusion, from a morning control baseline of 109.9 +/- 8.8 to 53.7 +/- 3.2 ng/ml after the infusion (P less than 0.05). Concomitant infusion of the AVP antagonist prevented the IL-1 alpha-induced LH inhibition (morning control baseline, 144.5 +/- 6.8; postinfusion, 132.3 +/- 5.8; P = NS vs. saline; P less than 0.0001 vs. IL-1 alpha). While cortisol concentrations decreased throughout the experimental period in the animals receiving saline, they increased after IL-1 alpha infusion: mean +/- SE postinfusion cortisol concentrations were 29.6 +/- 1.9 micrograms/dl (saline) vs. 44.0 +/- 1.7 micrograms/dl (IL-1 alpha; P less than 0.0001). Coinfusion of AVP antagonist and IL-1 alpha did not block the IL-induced cortisol increase (46.8 +/- 1.5 micrograms/dl; P less than 0.0001 vs. morning). After the infusion of AVP antagonist alone, cortisol concentrations significantly decreased from a morning control value of 40.2 +/- 1.6 to 34.9 +/- 1.6 micrograms/dl (P less than 0.05). The results confirm our previous demonstration of an inhibitory effect of IL-1 alpha on gonadotropin secretion in the ovariectomized rhesus monkey and indicate for the first time an important inhibitory role for AVP in the control of gonadotropin secretion during stress. The data also suggest that in this species, the adrenocortical response to IL-1 does not require AVP. PMID- 1611996 TI - Inherited congenital adrenal hyperplasia in the rabbit: absent cholesterol side chain cleavage cytochrome P450 gene expression. AB - We investigated adrenal steroidogenic enzymes, their activity and mRNA expression, and in vitro biosynthesis of an enzyme in rabbits with congenital adrenal hyperplasia (CAH; weight: CAH, 19 +/- 5 mg/adrenal; normal, 2.7 +/- 1.0 mg/adrenal). Serum pregnenolone (delta 5-P) levels in CAH newborn rabbits (12-36 h) were normal (mean/range, 438/51-2191 ng/dl), but corticosterone levels were low [0.05 +/- 0.05 microgram/dl; P less than 0.001 vs. normal (0.66 +/- 0.57)]. Serum Na+ levels in CAH newborn rabbits were in the normal range (143 +/- 30 meq/liter), but K+ levels were elevated [7 +/- 1.1 meq/liter; P less than 0.05 vs. normal (5.9 +/- 0.6 meq/liter)]. Minced normal adrenal tissue incubated with [3H] cholesterol (30-100 pmol/flask) and ACTH (100 mU/flask) produced [3H]delta 5 P (newborn, 21 and 45 fmol/100 mg; adult, 3 and 5 fmol/100 mg) and [3H]corticosterone (newborn, 23 fmol/100 mg; adult, 11.3 fmol/100 mg), but CAH adrenals produced no product (less than 1.3 fmol/100 mg). Adrenal mitochondria from normal newborn rabbits produced delta 5-P (4.4-7 nmol/mg protein), but CAH adrenals did not, while CAH adrenal mitochondria demonstrated over 4 times greater 11 beta-hydroxylase activity. A Western blot of adrenal homogenate from normal newborn rabbits revealed a cholesterol side-chain cleavage cytochrome P450 (P450scc)-immunoreactive species (mol wt, 53 x 10(3), but this species was absent in CAH adrenals; CAH adrenals had a normal adrenodoxin and intensified 17 alpha hydroxylase cytochrome P450 (P450(17)alpha) band compared to normal adrenals. In vitro translation of RNA in a cell-free rabbit reticulocyte lysate system containing [35S] methionine yielded a precursor P450scc protein (mol wt, 58.5 x 10(3)) with normal adrenal RNA, but not with CAH adrenal RNA. P450scc mRNA was detected in all normal adrenals, but was not detected in all CAH adrenals. 21 Hydroxylase cytochrome P450 mRNA expression was detected at a similar level in both normal and CAH adrenals. We conclude that CAH in the rabbit is caused by inherited absent P450scc gene expression. The clinical, pathological, and biochemical manifestations of P450scc deficiency in the rabbit are nearly identical to the human disorder. Increased 11 beta-hydroxylase activity and increased P450(17)alpha on Western blot of CAH adrenals indicate altered gene expression of other steroidogenic enzymes due to CAH. Further molecular analysis of the P450scc gene in this animal CAH model will facilitate understanding of P450scc deficiency CAH. PMID- 1611997 TI - Tissue iodothyronine levels in fetuses of control and hypothyroid rats at 13 and 16 days gestation. AB - Some investigators have reported that there is minimal placental transport of thyroid hormones in humans and rats. Consequently, it was thought that thyroid hormones were not present in the fetal brain before fetal thyroid hormone synthesis and, hence, were not important for brain development before fetal thyroid hormonogenesis. Recently, however, thyroid hormones have been detected by 14 days postconception (dpc) in the rat fetus and by 11 dpc in the rat embryotrophoblast. Thyroid hormone receptors have been shown in the fetal rat by 14 dpc. The present experiments were designed to determine if T4, T3, and their metabolites can be detected in rat fetuses at 13 and 16 dpc and if iodothyronines are selectively accumulated in fetal brain and liver. Furthermore, one group of dams was radiothyroidectomized before breeding to ascertain the effect of maternal hypothyroxinemia on fetal tissue iodothyronine concentrations. Tissue iodothyronines were extracted and measured by HPLC. T4, T3, rT3, and 3,5 diiodothyronine were well within the limits of detection by this procedure at both fetal ages. The only possible source of these hormones is the mother. In addition, if maternal serum T4 levels are low, fetal tissue T4 and T3 levels are low. The presence of high intracellular T3 levels, even at 13 dpc, shows that 5' monodeiodination occurs in the midgestational fetus. Intracellular hormone measurements show that T3, rather than rT3, is the predominant intracellular iodothyronine in the rat fetus. Both brain and liver selectively accumulate T4 and T3, supporting the observations of others that fetal thyroid hormone receptors are present in midgestation. The presence of thyroid hormones in fetal rat brain by 13 dpc coupled with the observation that hormone receptors are present by 14 dpc suggests that thyroid hormones do play a role in midgestational brain development. These data show that normal maternal serum thyroid hormone levels are important during midgestation to provide adequate thyroid hormones to the fetus. PMID- 1611998 TI - Progesterone blocks the estradiol-induced gonadotropin discharge in the ewe by inhibiting the surge of gonadotropin-releasing hormone. AB - Previous studies indicate an elevation of circulating progesterone blocks the positive feedback effect of a rise in circulating estradiol. This explains the absence of gonadotropin surges in the luteal phase of the menstrual or estrous cycle despite occasional rises in circulating estradiol to a concentration sufficient for surge induction. Recent studies demonstrate estradiol initiates the LH surge in sheep by inducing a large surge of GnRH secretion, measurable in the hypophyseal portal vasculature. We tested the hypothesis that progesterone blocks the estradiol-induced surge of LH and FSH in sheep by preventing this GnRH surge. Adult Suffolk ewes were ovariectomized, treated with Silastic implants to produce and maintain midluteal phase concentrations of circulating estradiol and progesterone, and an apparatus was surgically installed for sampling of pituitary portal blood. One week later the ewes were allocated to two groups: a surge induction group (n = 5) in which the progesterone implants were removed to simulate luteolysis, and a surge-block group (n = 5) subjected to a sham implant removal such that the elevation in progesterone was maintained. Sixteen hours after progesterone-implant removal (or sham removal), all animals were treated with additional estradiol implants to produce a rise in circulating estradiol as seen in the follicular phase of the estrous cycle. Hourly samples of pituitary portal and jugular blood were obtained for 24 h, spanning the time of the expected hormone surges, after which an iv bolus of GnRH was injected to test for pituitary responsiveness to the releasing hormone. All animals in the surge induction group exhibited vigorous surges of GnRH, LH, and FSH, but failed to show a rise in gonadotropin secretion in response to the GnRH challenge given within hours of termination of the gonadotropin surges. The surges of GnRH, LH, and FSH were blocked in all animals in which elevated levels of progesterone were maintained. These animals in the surge-block group, however, did secrete LH in response to the GnRH challenge. We conclude progesterone blocks the estradiol induced gonadotropin discharge in the ewe by acting centrally to inhibit the surge of GnRH secreted into the hypophyseal portal vasculature. PMID- 1611999 TI - Circulating bioactive follicle-stimulating hormone and less acidic follicle stimulating hormone isoforms increase during experimental induction of puberty in the female lamb. AB - The pubertal process with its multifaceted neuroendocrine control provides an excellent model for the study of the regulation of FSH heterogeneity. We tested the hypothesis that during the pubertal transition in the female lamb 1) an increase in both pituitary and circulating bioactive FSH concentrations occur and 2) that the increase in bioactivity is associated with a change in the distribution pattern of both pituitary and circulating FSH isoforms. Pituitary and serum immunoreactive (I), and bioactive (B, Sertoli cell bioassay) FSH concentrations were measured in six prepubertal lambs (18 +/- 1 weeks, 29.9 +/- 2.8 kg body weight; mean +/- SE) and compared to those of six others (24.2 +/- 2.2 weeks of age, 41.4 +/- 2.5 kg body weight) during the pubertal transition period. Puberty was synchronized by pulsatile iv administration of GnRH (2 ng/kg every 2 h for 24 h and then at hourly intervals for the next 12 h) in a manner mimicking the I-LH pulse patterns observed during the natural transition to adulthood. Blood samples were collected at 12-min intervals for 4 h from both groups of lambs; for the pubertal group this included the final 32-36 h of GnRH administration. At the end of the study, a 25 ml volume of peripheral blood was collected from both prepubertal and pubertal females for the determination of serum FSH distribution patterns; the lambs were then euthanised, and pituitaries were removed for determination of pituitary hormone content and FSH isoform distribution patterns. In addition, the distribution pattern of I-FSH isoforms in the pituitary and serum from both groups of lambs were compared. The pubertal stages of all lambs were verified by measuring the size of follicles, the circulating concentrations of estradiol (E2) and inhibin, and the I-LH pulse patterns. Prepubertal lambs had low frequency I-LH pulses, small (2-3 mm) size ovarian follicles and low circulating concentrations of E2 (4.1 +/- 0.4 pg/ml) and inhibin (38.0 +/- 2.9 U/ml WHO). By contrast, all the pubertal lambs had hourly I-LH pulse frequency (induced with exogenous GnRH), a large (5-6 mm) follicle (in one lamb a 4-mm follicle), follicular phase levels of E2 (7.1 +/- 0.8 pg/ml), and higher concentrations of inhibin (53.2 +/- 3.1 U/ml).(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1612001 TI - Early induction of c-fos precedes increased expression of corticotropin-releasing factor messenger ribonucleic acid in the paraventricular nucleus after immobilization stress. AB - CRF plays a role in coordinating endocrine, physiological, and behavioral responses to stressful stimuli. Several kinds of stressors have been reported to induce an increase in CRF mRNA expression in the paraventricular nucleus of the hypothalamus (PVN). Recently, the expression of c-fos mRNA has shown promise as a useful tool for metabolic mapping at the cellular level, because various types of stimulation induce c-fos mRNA expression in specific neuron populations in various brain regions. The aim of the present study is to clarify a possible anatomical-temporal correlation between the early induction of c-fos and the enhanced expression of CRF mRNA after stress. Wistar male rats were exposed to immobilization stress for 60 min and killed before and 15, 30, 60, 90, 120, and 180 min after the beginning of immobilization. In situ hybridization was performed by hybridizing sections with 35S-labeled prepro-CRF and c-fos cRNA probes. Relative levels of CRF and c-fos mRNA were compared by estimating the number of grains over the PVN in emulsion-dipped autoradiograms. Rapid induction (within 15 min) of c-fos mRNA was noted in the parvocellular division of the PVN after immobilization stress. The level of c-fos mRNA peaked at 30 min, then gradually declined to the control level within 90 min after the beginning of stress [the number of grains over the PVN: control, 326 +/- 180; 15 min, 2091 +/- 680 (P less than 0.05 vs. control); 30 min, 3385 +/- 239 (P less than 0.05 vs. control)]. The distribution of c-fos mRNA was almost identical to that of CRF mRNA in the PVN. On the other hand, the time course of CRF mRNA induction was delayed to the c-fos mRNA expression. A significant increase in CRF mRNA levels was noted only 120 and 180 min after stress [the number of grains over PVN: control, 3868 +/- 221; 120 min, 5957 +/- 677 (P less than 0.05 vs. control); 180 min, 6600 +/- 450 (P less than 0.05 vs. control)]. The results demonstrate that increased expression of CRF mRNA is preceded by c-fos mRNA induction in the PVN after stress suggesting a role of c-fos in the activation of CRF gene expression. PMID- 1612000 TI - Muscarinic cholinergic stimulation elevates intracellular pH in chicken granulosa cells by a Ca(2+)-dependent, Na(+)-independent mechanism. AB - Various hormones and growth factors act at least in part by raising the cytosolic pH of the target cell. In the present studies we examined the influence of the muscarinic cholinergic agonist carbachol on intracellular pH (pHi) in chicken granulosa cells. The pHi in granulosa cells from the two largest preovulatory follicles of hens was determined spectrofluorometrically using the pH-sensitive dye 2',7'-bis-(carboxyethyl)- 5(6)-carboxyfluorescein (BCECF). Carbachol (0.1-2 mM) induced a concentration-dependent increase in pHi, which reached a maximum of 0.23 +/- 0.02 pH units at a concentration of 1 mM. Cytosolic alkalinization was observed within 10 min of the addition of carbachol and lasted over the 60-min observation period. The effect of carbachol was mimicked by acetylcholine (1 mM) and muscarine (1 mM), but not by nicotine (0.1 mM). The carbachol-induced alkalinization was blocked by pretreating the cells with the muscarinic cholinergic receptor antagonists atropine (1 and 10 microM) and pirenzepine (0.01 and 0.1 mM). The increase in pHi did not appear to be mediated by a conventional mechanism involving the Na+/H+ antiporter, because it was unaffected by replacement of extracellular Na+ with the nonpermeant choline chloride or the presence of antiporter inhibitors, such as amiloride, dimethylamiloride, or ethylisopropylamiloride. However, the mechanism required external Ca2+, but did not involve Ca2+ channels, because it was unaffected by the general Ca2+ channel blocker methoxyverapamil (50 microM). Thus, Ca(2+)-dependent and Na(+) independent intracellular alkalinization may be a part of the signalling mechanism by which muscarinic receptor activation regulates chicken granulosa cell function. PMID- 1612002 TI - Systemic administration of recombinant human growth hormone induces expression of the c-fos gene in the hypothalamic arcuate and periventricular nuclei in hypophysectomized rats. AB - The neuronal expression of the protooncogene c-fos could serve as a marker of neural activity. To identify the brain sites responding to GH, rat brains after systemic administration of recombinant human GH (rhGH) were processed for hybridization histochemistry for c-fos mRNA. Adult male Wistar rats were hypophysectomized 10 days before rhGH administration. After hypophysectomy, rats received sc cortisone acetate (0.5 mg/kg BW) and L-T4 (20 microgram/kg BW) daily. Four international units (1.33 mg) of rhGH were given iv through an indwelling right atrial cannula. Vehicle was administered to control animals. The rhGH treatment was accompanied by expression of the c-fos gene in the arcuate nucleus (ARC) of the hypothalamus. The accumulation of the c-fos mRNA was transient, reaching maximum values at 60 min and decreasing thereafter to reach control levels within 120 min after rhGH injection. Among control animals, c-fos gene expression was not detected in the ARC. The c-fos mRNA was also detected in the paraventricular nucleus after rhGH administration; however, it was comparable to that in control animals. When rhGH was administered twice at 40-min intervals, c fos gene expression was induced in the periventricular nucleus (PeV) as well as the ARC 40 min after the second rhGH injection. Throughout the studies, c-fos mRNA was not detected other than in the ARC, paraventricular nucleus, and PeV in the hypothalamus. In the ARC, distribution of the cells expressing the c-fos gene appears to overlap at least in part with somatostatin (SS) mRNA-containing cells. In the PeV, it appeared to correlate generally with the distribution of SS mRNA containing cells. The data suggest that GH feeds back on neurons of hypothalamic PeV and ARC expressing SS mRNA, and that c-fos expression is involved in the feedback mechanism. PMID- 1612003 TI - Vascular endothelial growth factor messenger ribonucleic acid expression in the primate ovary. AB - We studied the distribution of messenger RNA (mRNA) that encodes for vascular endothelial growth factor (VEGF) within the primate ovary by in situ hybridization and Northern analysis to determine if the presence of mRNA for this angiogenic factor is associated with structures within the ovary in which angiogenesis is thought to play a role in development and/or function. In situ hybridization to sections of cynomolgus ovaries with a 35S-labeled antisense RNA probe revealed specific tissue localization within the follicle as well as the corpus luteum, but not stromal tissue. Intense expression of mRNA for VEGF during the late follicular phase was confined to the maturing follicle which, we presume, was destined for ovulation. Hybridization within the corpus luteum exhibited a punctate pattern suggesting that there may be specific cells within the corpus luteum that express mRNA for VEGF. The expression of mRNA for VEGF during the early and late luteal phase of the menstrual cycle was studied by Northern analysis. Messenger RNAs were detectable at approximately 3.7 and 5.0 kb positions in corpora lutea collected during the early luteal phase of the menstrual cycle (days 3-5 postovulation). No hybridization signals were observed with RNA prepared from regressing corpora lutea (1-2 days following the onset of menses). The gonadotropic regulation of the expression of mRNA for VEGF in the corpus luteum was studied by treating monkeys with a potent GnRH antagonist during the midluteal phase of the menstrual cycle. Administration of the antagonist for 1 or 2 days did not alter the expression of mRNA for VEGF in comparison to corresponding controls. However, a 3-day treatment regimen brought about a significant reduction in the levels of mRNA for VEGF (P less than 0.01). These studies demonstrate a development-related expression of mRNA for VEGF in the ovary during the menstrual cycle and are consistent with the hypothesis that VEGF may play important roles in follicle selection and corpus luteum function in primates. PMID- 1612004 TI - Identification of hormone-binding regions of the luteinizing hormone/human chorionic gonadotropin receptor using synthetic peptides. AB - A comprehensive series of overlapping synthetic peptides have been used to study the relationship between the primary structure of the ovarian receptor for LH/human CG (hCG) and hormone binding. Twenty-four consecutive, overlap peptides that replicate the entire extracellular domain of the rat luteal receptor have been synthesized by standard solid-phase techniques on an automated synthesizer. Eight additional peptides from the extracellular domain and three peptides replicating the putative extracellular loop regions have also been synthesized. Each peptide was evaluated in RRAs for interaction with hCG by measuring its ability to competitively inhibit binding of 125I-hCG to membrane receptor. Twelve peptides were found to be potent in RRAs and caused a reduction of half-maximal binding of 125I-hCG at concentrations of 10-250 x 10(-6) M. The 12 active peptides (and adjacent inactive peptides) defined at least 4 independent receptor regions that can interact with hormone. One site near the NH2-terminus was localized to receptor residues Arg21-Pro38. Two more sites of hormone interaction were identified by peptides replicating residues Arg102-Thr115 and Tyr253-Phe272. A fourth binding region was identified in the third putative extracellular loop, replicated by rat luteal receptor peptide Lys573-Lys583. The amino acid sequences of the four active rat LH/hCG receptor regions were aligned and compared with published sequences for other glycoprotein hormone receptors. Three regions (Arg102-Thr115, Tyr253-Phe272, and Lys573-Lys583) showed high sequence homology with the human LH/hCG receptor, human TSH receptor, and rat FSH receptor and may represent contact sites for the alpha-subunit of hormone. The other binding region, Arg21-Pro38 had low sequence homology with the other glycoprotein hormone receptors and is postulated to be a binding determinant for beta-hCG/LH. This report demonstrates that synthetic overlap peptides of confirmed sequence can be used to successively identify hormone interaction sites of glycoprotein hormone receptors. PMID- 1612005 TI - Sites and patterns of absorption of 3,5,3'-triiodothyronine and thyroxine along rat small and large intestines. AB - It is clear that some thyroid hormone is absorbed from mammalian intestines, but numerous aspects of this process remain unresolved, including elucidation of the locations, extent and mechanisms of absorption, and the role of absorption in thyroid hormone economy. Our goal was to identify the sites and patterns and estimate rates of absorption of both tracer T4* and T3* comprehensively along the entire length of rat intestines, with normal contents included, to gain further insight into the role of this organ in whole-body thyroid hormone regulation. We measured absorption directly in situ in fed rats, using a variant of the classic intestinal loop technique used by others demonstrating absorption of T4 or of T3 from portions of rat intestines under various conditions. Rats were anesthetized, bile ducts were ligated, and absorption was measured from pylorus to anus, in 14 loops of intestines previously injected with T3* or with T4*, or with T3* and T4* injected in adjacent loops. Rats were maintained under otherwise approximately normal conditions, with intestines in situ and abdomen closed, until killing at 2 h. Excised loop radioactivity was measured and loops were homogenized, extracted, and chromatographed quantitatively to evaluate remaining and absorbed T3* and T4*. Absorption of both T3* and T4* were clearly present and were approximately uniform from all small and large intestinal sections, all containing normal intestinal contents, indicating that the entire organ is involved in whole-body thyroid hormone regulation. Furthermore, T3* and T4* were absorbed at approximately the same rate, adding to evidence reported by others for a simple diffusion absorption mechanism. PMID- 1612006 TI - Estrogen receptors in dendrites and axon terminals in the guinea pig hypothalamus. AB - The ultrastructural localization of steroid hormone receptors has been made possible by the development of immunocytochemical procedures using monoclonal antibodies. Estrogen receptor-immunoreactivity (ER-IR) in the brain is present most abundantly in neuronal nuclei when observed with light microscopy. However, we have also observed ER-IR in the perikarya and cytoplasmic processes of neurons. To determine the organelles with which the cytoplasmic ER-IR is associated, we developed a technique for ultrastructural visualization of ER-IR. Ovariectomized guinea pigs were perfused, brains vibratome-sectioned, and estrogen receptors immunostained by either an immunoperoxidase-diaminobenzidine technique or by an immunogold-streptavidin procedure, each followed by silver intensification. Electron microscopic analysis confirmed distribution of ER-IR throughout cell nuclei, but ER-IR was also observed in proximal and distal dendrites and rough endoplasmic reticulum. Most surprisingly, however, ER-IR was found in many axon terminals containing predominantly round, and in some cases, flattened clear synaptic vesicles. Parallel experiments examining the distribution of progestin receptors confirmed the localization at the same subcellular sites as for estrogen receptors. The results of this experiment corroborate our earlier findings of extranuclear steroid receptor immunoreactivity in the brain, and they suggest potential nongenomic sites of action for estradiol and progesterone in dendrites and axon terminals. PMID- 1612007 TI - Maturation of follicle-stimulating hormone gonadotropes during the rat estrous cycle. AB - FSH mRNA is transcribed after the onset of high FSH secretion during proestrus and estrus. Pituitary cell fractions separated by size and density were studied to determine if expression of FSH mRNA activity was predominantly in one subset during the estrous cycle and to determine the source and significance of "silent FSH" cells that secrete FSH, but store too little for detection. Pituitary cells were separated by centrifugal elutriation, plated, and then exposed to 0.1-1 nM [D-Lys6]GnRH for 3 h. Media were assayed for FSH by RIA, and the cells were fixed for immunocytochemistry or in situ hybridization. The percentages of immunoreactive FSH cells in unseparated populations increased from 8% at metestrus to 12% during proestrus. Percentages of cells with FSH beta mRNA showed the same rise; however, peak levels were higher (17%) during proestrus and estrus. Small cells with FSH beta mRNA were more frequent than those with antigens early in the cycle. The largest cell fractions contained 38-44% immunoreactive cells. Only 8-21% of these cells had FSH beta mRNA, except during the morning of proestrus (33%). The distribution analyses showed that the increment in immunoreactive FSH cells during diestrus initially stemmed from smaller subsets; however, over half of immunoreactive FSH cells were large by the evening of proestrus. During the time of active transcription of FSH mRNA, more than half of the cells with FSH beta mRNA were small or medium-sized. Thus, early in the cycle, FSH beta mRNA is transcribed in the smaller cells, which may be the source of the silent FSH cells reported in previous studies. During proestrus, smaller FSH cells also secreted as well if not better than those in the unseparated population or large fractions. When they secreted more than expected from their percentages of FSH cells, this response was interpreted to be due to either the presence of cells that are immunoreactively silent or the possible removal of autocrine or paracrine regulatory factors. PMID- 1612008 TI - Mullerian duct regression and antiproliferative bioactivities of mullerian inhibiting substance reside in its carboxy-terminal domain. AB - A 25-kilodalton dimeric carboxy-terminal fragment of the recombinant human Mullerian inhibiting substance protein (rhMIS) was produced by proteolytic cleavage with plasmin and purified by size-exclusion chromatography. The identity of the isolated dimer as the carboxy-terminal fragment was confirmed by gel electrophoresis and Western analysis. As was true of every sample of the holo molecule, all preparations of the carboxy-terminal domain of rhMIS (n = 10), when added in the 0.5-5.0 micrograms/ml range, exhibited a dose-dependent partial to complete regression of the 14.5-day fetal rat Mullerian duct in an organ culture assay. The carboxy-terminal dimer also inhibited, in a dose-dependent manner, the growth of A431 cells in monolayer cultures. Daily addition of 5, 10, or 20 micrograms carboxy-terminus for 3 days resulted in 0%, 25%, and 100% inhibition of cell proliferation, respectively. Similar and higher doses of holo rhMIS had no or inconsistent antiproliferative activity (0-34% inhibition), even though the preparations caused Mullerian duct regression. All amino-terminal fragments prepared using this separation protocol were found to be inactive in these assays. These findings suggest that the bioactivity of rhMIS as a regressor of fetal Mullerian ducts and an inhibitor of A431 cell growth resides in its carboxy terminal domain. These results indicate that the urogenital ridge tissue, but not A431 cells in culture, may be capable of cleaving intact MIS to a biologically active conformation. PMID- 1612009 TI - Temporal gene expression is restored concomitantly with germ cells in the experimentally regressed rat testis. AB - The present study was designed to examine the effect of hypophysectomy and subsequent testosterone administration on germ cell numbers and germ cell- and Sertoli cell-specific mRNA levels in adult rats. Rats were hypophysectomized and 4 weeks later received 24-cm testosterone-containing polydimethylsiloxane (PDS) implants. Sham-hypophysectomized rats received an empty PDS implant. At 0 and 3 days, and at 1, 2, 4, and 8 weeks, rats were killed. One testis from each rat (n = 4/group) was used to prepare total RNA; the other testis was used to enumerate stage VII-VIII germ cells. cDNA probes for germ cell and Sertoli cell products were used to monitor germ cell- and Sertoli cell-specific mRNAs on Northern blots. Four weeks after hypophysectomy (0 days), preleptotene and pachytene spermatocytes and round and elongating spermatids were reduced in number to 54%, 12%, 1%, and 0%, respectively, of the control values. Testosterone administration caused a time-dependent increase in germ cell numbers; after 8 weeks of testosterone treatment, preleptotene and pachytene spermatocytes and round and elongating spermatids were 75%, 79%, 74%, and 22%, respectively, of control values. Lactate dehydrogenase-C, phosphoglycerate kinase-2, protamine-1, and sulfated glycoprotein-2 mRNA levels (on a per micrograms RNA basis) were 34%, 34%, less than 1%, and 580% of control values, respectively, 4 weeks after hypophysectomy and 79%, 87%, 61%, and 192% of control values, respectively, after 8 weeks of testosterone treatment. Pachytene spermatocyte and round spermatid numbers increased, while Sertoli cell sulfated glycoprotein-2 mRNA levels decreased, with respect to 4 week hypophysectomy values, as early as 3 days after implantation of testosterone capsules. In contrast, germ cell (lactate dehydrogenase-C, phosphoglycerate kinase-2, and protamine-1) mRNA levels increased to the greatest extent between 1-4 weeks after the start of testosterone treatment and, after a short lag period, reflected increases in germ cell type and number. The results indicate that cell-specific mRNAs appear concomitantly with germ cell reappearance in a time-dependent manner in the testes of testosterone-treated hypophysectomized adult rats. PMID- 1612010 TI - Effect of bilateral lesions of the ovine fetal hypothalamic paraventricular nuclei at 118-122 days of gestation on subsequent adrenocortical steroidogenic enzyme gene expression. AB - Fetal adrenal steroid hydroxylase activity and messenger RNA (mRNA) expression increases concurrent with the preterm rise in fetal plasma cortisol during late gestation in sheep. By placing bilateral lesions of the fetal paraventricular nuclei (PVN) we have previously demonstrated that the fetal PVN is necessary for the initiation of parturition, the late gestation preparturient increase in fetal plasma cortisol and ACTH, and ACTH secretion in response to fetal hypoxemia and hypotension. The purpose of this study was to determine the role of the fetal PVN in the late gestation increase in expression of mRNA for 17 alpha-hydroxylase (P 450(17)alpha), side-chain cleavage (P-450SCC), 11 beta-hydroxylase (P 450(11)beta), 21 hydroxylase (P-450C21), and 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) in the fetal adrenal. Ovine fetuses were subjected to bilateral lesions of the PVN (Lx; n = 4) or sham lesions (Sh; n = 4) at 118-122 days gestational age (dGA). Lx fetuses were recovered by cesarean section at greater than or equal to 157 dGA; Sh fetuses were recovered immediately postbirth at normal term (146.5 +/- 0.9 dGA). In addition, uninstrumented fetuses were obtained at 145-147 dGA by cesarean section (n = 3). RNA obtained from individual fetal adrenals was subjected to Northern analysis. Lx of the fetal PVN decreased (P less than or equal to 0.05) mRNA for P-450(17)alpha and P-450SCC but did not affect adrenocortical mRNA for P-450C21, P-450(11)beta, or 3 beta-HSD compared to Sh. To determine if the differences observed between Lx and Sh for P-450(17)alpha and P-450SCC mRNA were due to the process of labor, we compared uninstrumented 145-147 dGA to Sh. No differences in adrenal mRNA content were observed for P 450(17)alpha or P-450SCC between these groups. We conclude that in late gestation fetal sheep an intact fetal PVN is necessary for normal gene expression of adrenocortical P-450(17)alpha and P-450SCC while P-450(11)beta, P-450C21, and 3 beta-HSD may be primarily regulated by factors not dependent upon a functional PVN. PMID- 1612011 TI - Vanadate treatment markedly increases glucose utilization in muscle of insulin resistant fa/fa rats without modifying glucose transporter expression. AB - The present study examined the effects of chronic treatment with vanadate on in vivo insulin-stimulated glucose uptake by various tissues of obese and insulin resistant fa/fa rats. It further determined whether the substantial improvement induced by vanadate administration was associated with altered expression of the insulin-responsive glucose transporter (GLUT4). Since oral Na3VO4 caused decreases in food intake and body weight, vanadate-treated fa/fa rats were compared with controls, fed ad libitum, and pair-fed rats. The animals in the three groups were submitted to hyperinsulinemic clamps combined with the 2 deoxyglucose method. At similar levels of imposed hyperinsulinemia, the glucose infusion rate (milligrams per kg.min-1) required to maintain euglycemia, extremely low in controls (0.8 +/- 0.3) and pair-fed rats (1.2 +/- 0.6), was strikingly improved in vanadate-treated rats (9.5 +/- 0.3). Correspondingly, the insulin-mediated glucose utilization indices were 2- to 3-fold higher in all types of muscle in treated rats: hindlimb skeletal muscle, diaphragm, and heart. Glucose utilization remained unaffected in white adipose tissue and jejunum, whereas it was increased by mere food restriction in brown adipose tissue of pair fed rats. The amounts of GLUT4 and GLUT4 mRNA were then measured in the insulin sensitive tissues of the three groups of animals. Vanadate treatment induced no change in GLUT4 mRNA or GLUT4 protein levels in any of the examined tissues. It even prevented the rise in GLUT4 protein expression caused by calorie restriction in brown adipose tissue of pair-fed rats. In conclusion, chronic administration of vanadate markedly increases the insulin-mediated glucose uptake in muscle of insulin-resistant fa/fa rats without altering GLUT4 number. A functional improvement of glucose transporters due to more efficient translocation and/or increased intrinsic activity or changes in the insulin signaling pathway is, thus, likely to play a major role in the beneficial effects of vanadate. PMID- 1612012 TI - Prolactin granulogenesis is associated with increased secretogranin expression and aggregation in the Golgi apparatus of GH4C1 cells. AB - The GH4C1 pituitary tumor cell line (GH cells) serves as a model system to study the role of the granins in the packaging of PRL into secretory granules. The number of secretory granules containing PRL and two members of the granin family, chromogranin-B (CgB) and secretogranin-II (SgII), can be hormonally manipulated. In the present study we have investigated whether 1) granulogenesis in GH cells is preceded by condensation of the granins and PRL in the Golgi; 2) granulogenesis is preceded by an increase in granin expression in GH cells; and 3) PRL and the granins aggregate in vitro under high calcium, low pH conditions. GH cells were treated for up to 3 days with 17 beta-estradiol (1 nM), insulin (300 nM), and epidermal growth factor (10 nM) and were fixed in 4% paraformaldehyde for immunocytochemistry or harvested for RNA isolation and Northern blot analysis. After 1 day of hormone treatment, there was a significant increase in staining for PRL and the granins in the Golgi apparatus, which was identified using an antibody to MG-160. After 3 days of hormone treatment, PRL and granin staining was also found in a perinuclear region that was not stained with anti-MG-160 antibody, most likely representing secretory granules. An increase in PRL and granin expression contributed to increased Golgi staining, as the steady state levels of CgB, SgII, and PRL mRNA increased 186 +/- 14%, 203 +/- 7%, and 337 +/- 5% above control levels, respectively, within 6 h after hormone treatment. An in vitro aggregation system was used to determine whether PRL and the granins coprecipitate under high calcium, low pH conditions, which are thought to be characteristic of the trans-Golgi and secretory granules. Aggregation of the granins CgB and SgII was negligible during overnight dialysis against a buffer containing 150 mM NaCl and 10 mM 2[N-morpholino]ethanesulfonic acid-NaOH (pH 5.5) in the absence of calcium. There was significant aggregation of PRL under these conditions. When dialysis was performed in the presence of 10 mM CaCl2, PRL, CgB, and SgII coaggregated. This study indicates that increased expression and aggregation of the granins is associated with PRL granulogenesis in hormone-treated GH cells. However, the role of the granins may not be obligatory, as some cells can store PRL in the absence of detectable levels of CgB and SgII, and PRL has the capacity to self-aggregate. PMID- 1612013 TI - The identification, purification, and characterization of a pancreatic beta-cell form of the microtubule adenosine triphosphatase kinesin. AB - Microtubules have been implicated as being necessary for the secretion of insulin from beta-cells, although the mechanism by which cytoplasmic microtubules contribute to the release of insulin is unknown. Kinesin is a microtubule dependent adenosine triphosphatase (ATPase) that is thought to be responsible for the intracellular transport of vesicles and organelles. In this manuscript, the purification and preliminary characterization of a beta-cell form of kinesin is described. A 120-kilodalton antikinesin-reactive polypeptide was identified on blots when cultured insulinoma tumor cell lines were subjected to immunoblot analysis using monoclonal antibodies specific for the heavy chain of mammalian kinesin. The beta-cell form of kinesin was isolated from solid rat insulinoma tumors by cosedimentation of the kinesin with microtubules from tissue homogenates in the presence of adenylyl-imidodiphosphate. The beta-cell kinesin was further purified by gel filtration chromatography, and then the pure enzyme was characterized using in vitro assays. Although beta-cell kinesin showed little ATPase activity alone, the enzyme exhibited considerable ATP hydrolysis activity in the presence of taxol-stabilized microtubules. Moreover, in motility assays beta-cell kinesin was able to translocate microtubules across microscope coverslips in the presence of Mg(2+)-ATP. In summary, we report the identity of a novel islet beta-cell form of the microtubule-dependent ATPase kinesin and suggest a possible contribution of the microtubule cytoskeleton in insulin secretion. PMID- 1612014 TI - Modulation of growth hormone secretion by thermogenically derived free fatty acids in the perinatal lamb. AB - To evaluate the hypothesis that the rapid fall in circulating GH concentrations at birth is secondary to the initiation of nonshivering thermogenesis and the consequent rise in FFA levels, a series of experiments was performed in late gestation fetal sheep. By sequentially cooling the fetus by means of a coil placed around the fetal thorax, ventilating with oxygen via an exteriorized tracheostomy tube, and separating the fetus from the placenta by occluding the umbilical cord, nonshivering thermogenesis could be induced in utero. In the first protocol (n = 6) cooling alone had no effect on fetal plasma FFA levels, oxygenation elevated FFAs slightly from 64 +/- 7 mu Eq/liter to 183 +/- 29 mu Eq/liter, and cord occlusion caused a further marked rise (P less than 0.005) to 635 +/- 69 mu Eq/liter. Neither cooling nor ventilation affected fetal plasma GH concentrations which fell (P less than 0.001) from 160 +/- 17 ng/ml to 65 +/- 13 ng/ml upon cord occlusion. When the cord occluder was removed FFA levels fell (P less than 0.001) and GH concentrations rose (P less than 0.001) once more, and when the cord was again occluded FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001). In a second protocol nine fetuses were cooled, ventilated, and the umbilical cord occluded. Once more, plasma FFA levels rose (P less than 0.001) and GH concentrations fell (P less than 0.001); when thermogenesis was inhibited by the infusion of the adenosine agonist N6-(L-2 phenyl isopropyl)-adenosine, FFA levels fell from 725 +/- 88 mu Eq/liter to 265 +/- 56 mu Eq/liter and GH concentrations rose from 54 +/- 13 ng/ml to 323 +/- 73 ng/ml. In two further protocols the possibility that PIA was acting directly on GH secretion was excluded in six fetuses with low plasma FFA levels and in three fetuses with elevated plasma FFA levels secondary to a fatty acid emulsion infusion. These studies provide direct evidence that the pattern of change in plasma GH concentrations at birth in the sheep is determined in part by the rise in plasma FFAs of thermogenic origin. PMID- 1612015 TI - The rat placenta and the transfer of thyroid hormones from the mother to the fetus. Effects of maternal thyroid status. AB - We have studied the effects of maternal thyroid status on the effectiveness of the rat placenta near term as a barrier for the transfer of T4 and T3 to the fetus. Dams were given methimazole to minimize the fetal contribution to the T4 and T3 pools, so that the iodothyronines found in the conceptus are ultimately of maternal origin. The dams were infused with saline, or with T4 or T3 at doses ranging from 2.3-27.8 nmol T4 and from 0.77-20.7 nmol T3/100 g BW per day. A group of normal pregnant dams (C) was included. At 21 days of gestation T4, T3, and rT3 were measured by RIA in maternal and fetal plasma, and in maternal and fetal sides of the placenta. The total fetal extrathyroidal T4 and T3 pools were also determined. The dose-related changes in T4, T3, and rT3 levels in the placenta confirm the presence of both inner and outer ring iodothyronine deiodinase activities, and suggest increasing accumulation of the iodothyronines. Despite this, fetal extrathyroidal T4 and T3 increase progressively in T4-infused groups as a function of maternal circulating T4 levels. Fetal extrathyroidal T3 increases progressively in T3-infused groups as a function of maternal plasma T3. There was no evidence that the net maternal contribution of T4 or T3 would be proportionally less when the maternal pools became very high. It was concluded that the rat placenta is only a limited barrier for the transfer of T4 and T3 to the fetus. PMID- 1612016 TI - New functional zonation in the ovary as shown by immunohistochemistry of luteinizing hormone receptor. AB - Monoclonal anti-LH receptor antibodies were used to study receptor distribution in the various structures of porcine ovary. Primordial and primary follicles were not labeled. Immunoreactivity appeared on the thecal cells of secondary follicles of approximately 100-200 microns in diameter. In large antral follicles and preovulatory follicles granulosa cells were also labeled, whereas two zones were observed in the theca interna. The region close to the lamina basalis (approximately 1/3 of the thecal cells) appeared devoid of LH receptors, whereas a strong labeling was observed on the most external region. Thecal cells were also labeled in atretic follicles. There was no labeling of the oocyte. In cyclic corpora lutea only the most external cells, probably of thecal origin, were stained. The most abundant cells, of granulosa origin, were not labeled. In the interstitium few cells were immunolabeled; they proceeded either from remnants of atretic follicles or existed as groups of isolated cells. Thus both the theca interna of preovulatory follicles and the corpus luteum are heterogenous structures composed of two zones of which only one is directly responsive to LH. No LH immunoactivity could be detected in nontarget organs (liver, lung, thyroid gland, small intestine, fallopian tube, and uterus). PMID- 1612017 TI - Characterization of nuclear angiotensin-II-binding sites in rat liver and comparison with plasma membrane receptors. AB - Although the action of angiotensin-II (Ang-II) is believed to be mediated by a transmembrane signal transduction mechanism, accumulating evidence suggests that Ang-II may also have a direct nuclear action. We have characterized the nuclear Ang-II-binding site in purified nuclei preparation from rat liver and compared it to plasma membrane Ang-II receptors. [125I]Ang-II binding to isolated nuclei reached equilibration in 30 min at 25 C, slower than binding to plasma membrane, which reached equilibration within 10 min. Scatchard analysis of [125I]Ang-II binding to isolated nuclei revealed a single class of binding sites (Kd = 1.4 nM; binding capacity = 10 fmol/mg protein or 460 sites/nucleus). In the nuclear preparation, Ang-II and its fragments competed for binding a potency order of Ang III = Ang-II greater than Ang-II-(1-7) greater than Ang-II-(1-6) greater than Ang II-(1-5). Losartan potassium (DuP 753), a selective blocker of the Ang-II receptor subtype I, fully inhibits nuclear Ang-II binding with affinity similar to that in plasma membrane. The pH optimum for [125I]Ang-II binding to nuclei was 7.0, while binding to plasma membrane was optimal at pH 8.0. Low concentrations (0.05-0.1 mM) of dithiothreitol increased [125I]Ang-II binding to nuclei, but not to plasma membrane. In the absence of detergent, Ang-II-binding sites appear to consist of soluble protein releasable from nuclei by freezing and thawing, hence distinct in physicochemical properties from the membrane-bound receptor. Size exclusion HPLC estimated the mol wt of the soluble Ang-II-binding sites to be 66 kilodaltons. These nuclear Ang-II-binding sites have some similarities to but also show notable physicochemical differences from plasma membrane Ang-II receptors, and they may play a role in mediating the intracellular action of Ang II. PMID- 1612018 TI - Estrogen receptor messenger ribonucleic acid in female rat brain during the estrous cycle: a comparison with ovariectomized females and intact males. AB - Variations in levels of estrogen receptor mRNA were investigated in the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus throughout the phases of the female estrous cycle and compared with those in ovariectomized female and intact male rats. Female Wistar rats were killed during estrus, metestrus, diestrus, or proestrus or 72 h after ovariectomy as were a group of intact male rats. Brains were removed and frozen, and 20-microns cryostat sections were thaw-mounted onto slides and hybridized with a 35S-labeled antisense estrogen receptor probe. Section-mounted slides were processed, apposed to x-ray film, then dipped in liquid emulsion, and quantified. After exposure, estrogen receptor mRNA was detected in several brain regions, including the medial preoptic nucleus, arcuate nucleus, and ventromedial nucleus of the hypothalamus. Estrogen receptor mRNA levels in the medial preoptic nucleus were highest during estrus and metestrus, attenuated at diestrus, and low during proestrus. In contrast, the hybridization signal in the arcuate and ventromedial nuclei was low during estrus and then gradually increased throughout the cycle until it peaked during proestrus. Ovariectomized females exhibited an elevated level of estrogen receptor mRNA in all brain regions investigated. Hybridization signal in male medial preoptic nucleus and ventromedial nucleus was reduced compared with those in both intact and ovariectomized females. Estrogen receptor mRNA levels in the arcuate nucleus were similar to those in intact females, but less than those in ovariectomized animals. The results of these studies demonstrate that estrogen receptor mRNA levels are sexually dimorphic, vary during the estrous cycle, and increase after ovariectomy. Furthermore, these results indicate that the magnitude and direction of change observed during the estrous cycle are region specific and suggest that factors other than endogenous estrogen levels differentially modulate estrogen receptor mRNA expression in the hypothalamus. PMID- 1612019 TI - Role of dopamine in the regulation of gonadotropin-releasing hormone in the male rat brain as studied by in situ hybridization. AB - The effects of the dopaminergic antagonist haloperidol (HAL) as well as the D2 dopamine receptor agonist bromocriptine (BRO) on GnRH messenger RNA (mRNA) levels in the male rat were investigated by quantitative in situ hybridization. Since it had already shown that androgens could induce a decrease in GnRH mRNA levels in castrated rats, the involvement of the dopaminergic system in the inhibitory effect of dihydrotestosterone (DHT) was also investigated. In situ hybridization was performed on paraformaldehyde-fixed cryostat sections through an area extending from the preoptic area to the anterior hypothalamus using a 35S-labeled 48-base oligodeoxynucleotide complementary to the GnRH coding region of the GnRH DNA. The corresponding mRNA levels were assessed by counting the number of silver grains overlying labeled neurons. In intact animals, a 14-day treatment with BRO increased by 67% the number of silver grains per neuron while HAL decreased by 31% the value of this parameter. Hypophysectomy which induced a 22% decrease in the hybridization signal could not prevent the effects of BRO or HAL. Gonadectomy performed 14 days earlier increased by 54% the mean number of silver grains while a 14-day treatment of gonadectomized animals with DHT decreased the hybridization signal by 48%. On the other hand, the concomitant administration of HAL and DHT did not prevent the inhibitory effect of DHT but rather resulted in a decrease of the hybridization signal which was more marked than that induced by DHT or HAL alone. The present data clearly demonstrate that GnRH mRNA levels are positively regulated by dopamine and that the effects of BRO and HAL on GnRH mRNA are not mediated by variations in pituitary hormone secretion. Moreover, our results suggest that the effect of DHT on GnRH gene expression is probably not mediated by the dopaminergic system. PMID- 1612020 TI - Remembrance: Leslie L. Iversen, Merck Sharp & Dohme Research Laboratories, Neuroscience Research Centre, Harlow, England. "The Axelrod Lab, 1964-1965". PMID- 1612021 TI - Effect of thyroid hormone treatment on redox and phosphate potentials in rat liver. AB - In the present study rat liver cytosolic/mitochondrial redox and phosphate potentials were evaluated as a function of thyroid hormone status. T3 treatment resulted in a dose-dependent 2-fold decrease in the cytosolic redox potential, as reflected by the liver lactate/pyruvate ratio, with a concomitant increase in the liver capacity of handling an ethanol load. The effect of T3 on liver cytosolic redox potential was correlated with a T3-induced increase in mitochondrial glycerol-3-phosphate dehydrogenase activity. The apparent liver cytosolic phosphate potential was calculated from the glycerol-3-phosphate/3 phosphoglyceric acid ratio, using 31P-nmr under conditions of rapid equilibrium within the glycerol-3-phosphate/3- phosphoglyceric acid metabolic section and was found to be essentially unaffected by T3 treatment. The apparent total cellular phosphate potential measured by 31P-nmr, however, was decreased in T3-treated animals, reflecting a decrease in the apparent liver mitochondrial phosphate potential induced by T3 treatment. Also, while the apparent cellular phosphate potential of euthyroid rats was independent of ethanol administration, the reduced cellular phosphate potential of T3-treated rats was normalized by ethanol treatment. In conclusion, thyroid hormone treatment induces in vivo a dramatic decrease in the liver cytosolic redox potential, with a concomitant increase in the liver oxidizing capacity. The decrease in cytosolic redox potential induced by thyroid hormone treatment is accompanied by a decrease in mitochondrial phosphate potential. Liver mitochondrial ATP production in thyroid hormone treated animals appears to be rate limited by the availability of cytosolic reducing equivalents. PMID- 1612022 TI - Expression of thyroglobulin gene in maternal and fetal thyroid in rats. AB - The relationship between the changes in thyroglobulin (Tg) mRNA and Tg proteins during thyroid development in the fetus and in maternal thyroid glands during gestation and lactation is studied. While the appearance of Tg mRNA (fetal day 15) showed good temporal correlation with that of 12S Tg, no 19S Tg could be detected until 3 days later. The 12S Tg was the predominant protein on days 18 and 19 of gestation in the fetus, while 19S Tg was the predominant protein on fetal days 21-22 and during the postnatal period in the offspring; by the 20th postnatal day, the 19S Tg content per gland was 4 times the amount of 12S (155 vs. 37 micrograms/gland; P less than 0.001). The 19S iodine content in the fetus was the same as that in 12S up to the 21st day of gestation, except for lower values on day 18. From fetal day 22 and through the postnatal period, the iodine content in 19S was 1.6-5.9 times greater than that in 12S. Therefore, the ratio of atoms of iodine per mol Tg during the experimental period changed from 0.75 to 19.5 for 19S and from 0.72 to 7.2 for 12S. The levels of all of the iodoamino acids were low on fetal days 17-19, after which they increased at different rates for each protein. The greatest increase in monoiodotyrosine and T3 corresponded to 12S, while diiodotyrosine and especially T4 showed a greater increase in 19S than in 12S Tg; 20 days after birth, the T4 content in 19S was about 3 times greater than that in 12S Tg. The soluble thyroid proteins from pregnant, lactating, and nonpregnant female controls contained a main protein, 19S, and a smaller amount of 27S. Both 19S Tg and 19S iodine contents were already lower than those in nonpregnant rats at 14 days of pregnancy, and the levels continued to decrease during the experimental period. In contrast, the 27S Tg and 27S iodine levels remained constant and similar to nonpregnant values. Surprisingly, a decrease in the level of Tg mRNA was observed during pregnancy and lactation. We have no explanation for the dramatic decrease in Tg mRNA during the last days of pregnancy. Further studies should help to elucidate the mechanism responsible for the changes in Tg gene expression in the thyroids of pregnant and lactating rats. PMID- 1612023 TI - Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor-I. AB - GH secretion in the male rat is characterized by regular GH peaks of high amplitude, and their GH receptors and GH-binding protein (BP) are low. Female rats have a more continuous secretion, and their GH receptors and GH-BP are high. To determine how the pattern of GH delivery may affects the physiological responses to the hormone, hypophysectomized male rats were infused with human GH (1.5 U/kg.day) for 5 days through an implanted iv cannula in either a pulsatile manner (for 5 min every 3 h) or continuously. We then measured free and total (after MgCl2 treatment) somatogenic and lactogenic receptors in hepatic cell membranes, and GH-BP and immunoreactive insulin-like growth factor-I (IGF-I) in serum. The concentrations of occupied, but not free, somatogenic and lactogenic binding sites were higher 5 min after a 5-min infusion of human GH than 90 min after the infusion. Consequently, the total levels (free plus ligand binding) of somatogenic and lactogenic receptors were also higher 5 min after a GH pulse than after 90 min. The levels of circulating GH-BP were higher 90 min than 5 min after a GH pulse, and the serum IGF-I levels did not differ between these time points. The concentrations of free and total somatogenic and free lactogenic receptors in the liver, as well as GH-BP and IGF-I in circulation were higher and body weight gain was lower in rats given continuous GH infusion than after pulsatile infusions. It is concluded that the nature of GH-levels profile has a marked influence on the interrelationship of GH, GH receptors, GH-BP, serum IGF-I and growth, whereby the later is stimulated maximally by pulsatile GH-levels, while the receptor and GH-BP are enhanced maximally by continuous levels. The basis for this discrepancy may lay in the competitive power of GH-BP toward GH receptor binding. A pulsatile GH pattern induced cyclicity in the levels of hepatic cell membrane GH receptors and circulating GH-BP. It is suggested that these factors are regulated in a similar way by the plasma GH pattern in pituitary intact rats. PMID- 1612024 TI - Growth hormone and insulin-like growth factor-I increase macrophage uptake and degradation of low density lipoprotein. AB - Hyperlipidemia has been reported in adults with hypopituitarism, and human (h) GH therapy has been shown to lower plasma cholesterol in patients with hypercholesterolemia. Macrophage cholesterol accumulation is an early event in atherosclerosis, and these cells have been shown to respond to GH and insulin like growth factor (IGF-I). The present study was aimed at investigating the activity of GH and IGF-I in macrophages, and used murine macrophages as a model system to investigate the effects of GH and IGF-I on cellular uptake and metabolism of low density lipoprotein (LDL). The J-774 murine macrophage cell line was shown to bind hGH, to respond to hGH by an increase in cell IGF-I content, and to have specific high affinity binding sites for IGF-I. Mouse peritoneal macrophages and the J-774 macrophage cell line respond to hGH with a dose-dependent stimulation of cellular association and degradation of LDL as well as an enhanced cholesterol esterification rate. A similar response was observed after in vitro treatment of the cells with IGF-I. Preliminary results in human monocyte-derived macrophages showed similar results. The dependency of the effect of hGH on locally produced IGF-I was shown by abrogation of the hGH effect after adding anti-IGF-I antibody to the culture medium. It is concluded that murine macrophages possess the machinery to bind GH, produce IGF-I, and bind IGF-I. This machinery is used by macrophages, and apparently by other cells, to execute GH dependent IGF-I-mediated stimulation of cellular uptake and metabolism of LDL. This may provide the explanation for both the elevated plasma LDL concentration in patients with GH deficiency and the effect of GH therapy to reduce plasma LDL levels. PMID- 1612025 TI - Mitotic activity of the endocrine cells in rat thyroid glands during postnatal life. AB - This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells. PMID- 1612026 TI - Transforming growth factor-beta blocks protein kinase-A-mediated iodide transport and protein kinase-C-mediated DNA synthesis in FRTL-5 rat thyroid cells. AB - Recent studies have shown that transforming growth factor-beta (TGF beta) alters DNA synthesis and iodide metabolism in human, porcine, and rat thyroid cells. In the present work we studied the mechanism of TGF beta action in FRTL-5 rat thyroid cells. The cells were treated with TGF beta in the presence of TSH, growth factors, and cellular modulators for various periods of time; then, [3H]thymidine incorporation and DNA content were measured as indicators of DNA synthesis, and [125I]iodide uptake was measured to assess cell function. TGF beta (10 ng/ml) inhibited TSH-induced DNA synthesis and iodide uptake. TGF beta also inhibited DNA synthesis induced by insulin-like growth factor-I, fibroblast growth factor, and endothelial cell growth factor. The protein kinase-A (PKA) activator 8-bromo-cAMP increased both iodide uptake and DNA synthesis; TGF beta inhibited 8-bromo-cAMP-induced [125I]iodide uptake, but not [3H]thymidine incorporation. The protein kinase-C (PKC) activator phorbol 12-myristate 13 acetate increased [3H]thymidine incorporation, and TGF beta inhibited this action of phorbol 12-myristate 13-acetate. The results show that activation of PKA or PKC increases DNA synthesis. TGF beta inhibited PKC-mediated, but not PKA mediated, DNA synthesis in these cells. The results also show that TGF beta selectively inhibits PKA-mediated iodide uptake, but not PKA-mediated DNA synthesis. These findings suggest that TGF beta is a strong inhibitor of the proliferation and function of thyroid cells. PMID- 1612027 TI - Transport of 3,5,3'-triiodothyronine into the perfused rat liver and subsequent metabolism are inhibited by fasting. AB - The effects of 48-h fasting on transport of T3 and subsequent metabolism in the isolated perfused rat liver were investigated. Tracer T3 disappearance curves from the recirculating medium consisted of a fast component (FC) and a slow component (SC). Using a two-compartment model, both transport [expressed as the fractional transport rate constant from medium to liver (k21)] and disposal of T3 were calculated. After fasting, k21, total metabolism, and metabolism corrected for differences in mass transfer were diminished, pointing to both decreased transport and metabolism, presumably caused by depletion of liver ATP. Concerning transport, it was shown that only transport into the intracellular liver compartment and not transport to the extracellular liver compartment was decreased after fasting. As for metabolism, T3 glucuronidation was diminished; T3 sulfation and subsequent deiodination were not affected. All mentioned decreased parameters normalized after the addition of a combination of insulin, cortisol, and/or glucose to the medium, possibly by (partially) restoration of cellular energy stores. PMID- 1612028 TI - Glucocorticoid regulation of transforming growth factor-beta activation in urogenital sinus mesenchymal cells. AB - The transforming growth factors-beta (TGF-beta s) regulate many aspects of cell proliferation and differentiation. The TGF-beta isoforms are produced by most cell types in the biologically inactive, latent form. The physiological relevance of latent TGF-beta and the regulation of activation to the biologically active form are not well understood. Although expression of TGF-beta messenger RNA is regulated by the steroid hormone family, the mechanisms of hormonal regulation of TGF-beta activation have not been well studied. Fetal rat urogenital sinus organ cultures and derived mesenchymal cell lines (U4F, U4F1) have been established in order to analyze the expression of growth and differentiation regulatory factors which may function in mesenchymal induction of epithelial differentiation. The U4F1 cell line in chemically defined medium upon supplementation with dexamethasone (10 nM-1.4 microM), produced an activity which was growth inhibitory to PC-3 prostatic carcinoma epithelial cells. Analysis of physicochemical properties and purification of activity demonstrated a 25-kDa protein was responsible for activity. The activity cross-reacted to antisera specific for TGF-beta 1, beta 2 and for TGF-beta 2 exclusively, but not with antisera to rat interferon (alpha-beta) or rat interleukin 6. Acid treatment of control (unsupplemented) conditioned medium and cultures supplemented with other steroid hormones produced identical levels of activated TGF-beta as nonacid treated conditioned medium from dexamethasone supplemented cultures which did not increase levels of activity upon acid activation. Activity from the acid-treated control conditioned medium was neutralized by TGF-beta antibodies. These data suggest latent TGF-beta is produced constitutively by U4F1 mesenchymal cultures in steroid unsupplemented medium and these cultures are induced by dexamethasone to activate identical levels of TGF-beta. These observations may be relevant to understanding diverse aspects of glucocorticoid regulation of tissue function and suggests that TGF-beta may be relevant to paracrine and autocrine growth regulation in the developing urogenital sinus. PMID- 1612029 TI - Selenium deficiency and type II 5'-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine. AB - Selenium deficiency in rats is characterized by elevated serum T4 and decreased serum T3 concentrations, and low liver type I (5'D-I) and brain type II (5'D-II) iodothyronine 5'-deiodinase activities. These findings are partially explained by the demonstration that type I 5'D is a selenoprotein; however, 5'D-II does not contain selenium. Since 5'D-II varies inversely with serum T4 concentrations, and serum T4 is elevated in selenium deficiency, the decreased cerebrocortical 5'D-II activity may be secondary to the increased serum T4 levels. To determine the mechanism(s) by which selenium influences 5'D-II activity, we examined the effects of altered selenium intake on brain 5'D-II levels and enzyme turnover in euthyroid and thyroidectomized rats. Rats were fed a selenium-supplemented or selenium-deficient diet for 5 weeks from weaning; half of the animals were also thyroidectomized 3 weeks before death. Selenium deficiency was confirmed by decreased liver and brain glutathione peroxidase activities. In euthyroid rats, selenium deficiency caused a 38% increase in serum T4, and 91% and 39% decreases in 5'D-I and 5'D-II, respectively, compared to those in selenium-supplemented rats. In the thyroidectomized hypothyroid rats, selenium deficiency caused a 60% decrease in 5'D-I, but had no effect on 5'D-II activity, fractional turnover of the enzyme, or the calculated enzyme synthesis rate. The lack of effect of selenium deficiency on 5'D-II levels in hypothyroid rats is consistent with the finding that 5'D-II is not a seleno-enzyme. Thus, the decrease in brain and pituitary 5'D-II activity in selenium-deficient euthyroid rats is due to the T4 dependent increase in the turnover of the enzyme polypeptide. PMID- 1612030 TI - Structural manifestations of the rat Sertoli cell to hypophysectomy: a correlative morphometric and endocrine study. AB - Although the Sertoli cell is a key cell mediating the actions of FSH- and LH stimulated testosterone (T) in the testis, there is little information to indicate how this cell responds structurally to hormonal insufficiency. The present study used morphometric techniques to study the structural manifestations of the Sertoli cell in adult rats hypophysectomized for 6 and 28 days. Six days posthypophysectomy, a period when germ cell degeneration is first evident, tubular diameter and length, testis weights, volume of the interstitium, and volume of most parameters that comprise the interstitium (except blood vessels) showed significant regressive features. However, virtually no parameter relating to the volume and surface area of the Sertoli cell or its subcellular components was significantly reduced compared with that in the normal animal. Thus, at a time when germ cell degeneration is seen in the testis, the Sertoli cell showed no significant structural response to the changing endocrine status of the animal. In contrast, 28 days after hypophysectomy, virtually all parameters relating to the Sertoli cell and its organelles were significantly decreased compared with those in normal animals. Plasma and tissue testosterone, PRL, and FSH showed a very significant decrease 6 days after hypophysectomy compared with intact animals, but at 28 days there was no further significant decrease in the levels of these hormones. There was no correlation of most organelle volumes and surface areas with endocrine parameters. The size of the Sertoli cell showed positive and significant correlations with the volumes and surface areas of all of its cytoplasmic organelles, except the lipid volume. Short term hypophysectomy resulted in no significant change in either the concentration (femtomoles per mg protein) or the content (femtomoles per testis) of FSH receptors, nor was there a significant change in the number of FSH receptors per cell. However, 28 days after hypophysectomy only the content, not the concentration, of FSH receptors decreased significantly along with a decrease in the number of FSH receptors per cell. Although the marked degenerative changes that are seen in the testis 6 days after hypophysectomy parallel endocrine decline, the Sertoli cell responded slowly from a structural standpoint compared with the Leydig cell. After long term hypophysectomy, significant morphometric changes were observed in all of its structural parameters. PMID- 1612031 TI - Structural changes in rat Leydig cells posthypophysectomy: a morphometric and endocrine study. AB - Short and long term responses of the rat Leydig cell were studied posthypophysectomy, at times when germ cell degeneration was first prominent (6 days) and after long term regression of the testis (28 days). In the short term, virtually all structural parameters relating to the volume and surface area of the Leydig cell and its subcellular organelles were significantly lowered compared with those in control animals. Exceptions were the volumes of the nucleolus, heterochromatin, and lysosomes and the surface areas of the nucleus. Structural decreases were generally on the order of 2- to 5-fold in the 6-day period. A statistical analysis of the percent decreases in the short term was performed to determine whether any particular structural features were more sensitive to hypophysectomy than any others. In most instances, no particular organelles were decreased compared to others. However, lipid, although not commonly seen in rat Leydig cells, showed significantly greater percent decreases compared with several other organelles, indicating that the small amount of lipid present is rapidly lost (used) in the short term. After long term hypophysectomy, all structural parameters of the Leydig cell were significantly lowered compared with those in pituitary-intact animals. Only a few parameters (mitochondrial volume, cell surface area, and the surface areas of inner and outer mitochondrial membranes and smooth endoplasmic reticulum) showed more significant decreases in the long term compared with the short term hypophysectomized animals. Most organelle volumes and surface areas correlated positively and significantly with serum and tissue testosterone levels; the exceptions were the volumes of the nucleolus, heterochromatin, lipid, and lysosomes. Compared with the pituitary intact animal, the content of LH receptors expressed per testis and per Leydig cell was significantly lower in both hypophysectomized groups; however, the number of receptors per given area of individual Leydig cell plasma membrane remained unchanged. Overall, data show that the Leydig cell manifests marked structural changes during early spermatogenic dysfunction. PMID- 1612032 TI - Renal phosphate transport and vitamin D metabolism in X-linked hypophosphatemic Gy mice: responses to phosphate deprivation. AB - Two closely linked, nonallelic genes, Gy and Hyp, result in X-linked hypophosphatemia in mice. The present studies in Gy mice were undertaken to determine whether renal brush-border membrane Na(+)-phosphate cotransport kinetics and adaptive responses of renal phosphate transport and vitamin D metabolism to phosphate deprivation are comparable in the two mutant strains. Transport studies in purified brush-border membrane vesicles over a phosphate concentration range of 10-500 microM demonstrated that the apparent maximum velocity of the high affinity transport system is significantly decreased in Gy mice (420 +/- 110 vs. 710 +/- 100 pmol/mg protein.6 sec, Gy vs. normal; mean +/- SE; P less than 0.05), whereas the affinity of the cotransporter for phosphate is unchanged (apparent Km, 25 +/- 3 vs. 27 +/- 2 microM; NS). Feeding a low phosphate diet results in a significant fall in plasma phosphate and an increase in brush-border membrane Na(+)-phosphate cotransport in both normal (568 +/- 40 to 1416 +/- 139 pmol/mg protein.6 sec; P less than 0.01) and Gy mice (407 +/- 27 to 1236 +/- 132 pmol/mg protein.6 sec; P less than 0.01). While the low phosphate diet elicited a rise in plasma 1,25-dihydroxyvitamin D in normal mice (51 +/- 12 to 158 +/- 12 pM; P less than 0.01), a fall in plasma hormone levels was evident in phosphate-deprived Gy mice (90 +/- 22 to 23 +/- 11 pM; P less than 0.01). Phosphate deprivation decreased 25-hydroxyvitamin D-24-hydroxylase (24 hydroxylase), the first enzyme in the renal vitamin D catabolic pathway, in normal mice (117 +/- 21 to 69 +/- 8 fmol/mg protein.min), but increased enzyme activity in Gy mice (172 +/- 14 to 240 +/- 18 fmol/mg protein.min; P less than 0.05). Moreover, under both dietary conditions, 24-hydroxylase activity was significantly elevated in Gy mice. The present results demonstrate that hypophosphatemia in Gy mice can be attributed to a decrease in the maximum velocity of the high affinity Na(+)-phosphate cotransport process in renal brush border membranes. Our results also show that while renal brush-border membrane phosphate transport is appropriately modulated by phosphate in Gy mice, phosphate regulation of vitamin D metabolism is apparently impaired in the mutant strain. The present findings provide evidence for phenotypic similarities between murine Gy and Hyp mutations. PMID- 1612033 TI - Proopiomelanocortin gene expression in a distinct population of rat spleen and lung leukocytes. AB - Existence of proopiomelanocortin (POMC) messenger RNA (mRNA) and related peptides in extrapituitary sites has been demonstrated in immune cells, although the particular type of immune cell has been the source of considerable debate. Specifically, double labeling studies have shown that POMC peptide expressing cells in the spleen represent a subpopulation of red pulp macrophages, while splenic lymphocyte areas are POMC negative. In addition, it has also been reported that peripheral blood leukocytes express the POMC gene. Using a sensitive solution hybridization technique with a POMC exon-1 RNA probe, we detected 70 +/- 20 fg and 65 +/- 5 fg POMC mRNA per microgram total RNA in whole spleen and lung, respectively, approximately 20,000-fold lower concentrations than found in the neurointermediate lobe of the pituitary. The presence of nuclease protected full length exon-1 bands, rather than the 5' truncated POMC RNAs seen in many nonpituitary tissues, indicates transcription initiation at the normal pituitary POMC promoter site in lung and spleen. In order to localize POMC gene expression in these tissues we employed an in situ hybridization method. There was an intense signal in a small population of large mononuclear cells scattered throughout the splenic red pulp and lung parenchyma. In the lung, these cells were concentrated in the periarteriolar zone in a manner suggestive of migration from the intravascular lumen. These cells had a histomorphology suggestive of monocyte-macrophages. POMC mRNA was undetectable in the splenic white pulp and bronchus-associated lymphoid tissue, indicating an absence of POMC gene expression in splenic and lung lymphocytes. Immunocytochemical studies suggested that POMC-positive cells made up a subpopulation of cells expressing the rat monocyte-macrophage markers ED1 and ED2. Similarly, the distribution of Jenner-Giemsa stained monocyte-macrophages appeared to overlap with POMC positive cells. Studies with anti-rat beta-endorphin antisera revealed scattered cells in the splenic red pulp and lung parenchyma, suggesting that the POMC mRNA is translated in these cells. In summary, POMC mRNA is expressed in a small population of monocyte-macrophage-like cells in lung and spleen but not in lymphocytes in these tissues. PMID- 1612034 TI - Transgenic female mice with high human growth hormone levels are fertile and capable of normal lactation without having been pregnant. AB - Transgenic mice carrying the phosphoenolpyruvate carboxykinase promoter region human growth hormone (PEPCK-hGH) fusion gene are characterized by accelerated growth and plasma hGH levels ranging from 100 to 700 ng/ml. Both sexes are fertile, in contrast to previous findings in metallothionein-I/hGH transgenic mice in which females are sterile, apparently due to luteal failure. Virgin transgenic PEPCK/hGH females from this line produce milk and can successfully raise foster litters to weaning. We conclude that the life-long presence of very large amounts of hGH in the circulation is compatible with ovulation, can override the effects of hGH-induced suppression of endogenous PRL release, and can support full lactation in animals that have not been primed by hormonal changes associated with pregnancy. PMID- 1612036 TI - Extracorporeal piezoelectric lithotripsy for retained bile duct stones. AB - Extracorporeal piezoelectric shock wave lithotripsy (EPL) was performed in 35 patients with endoscopically non-extractable stones. With this lithotripter, stones are visualized by ultrasound and shock waves are produced by a piezoelectric acoustic generator. The stones could be localized in 32 out of 35 patients. Fragmentation was achieved in 91.4% and complete stone removal in 77.1%. These results show that piezoelectric lithotripsy is also a useful method for the treatment of complicated bile duct stones, as already demonstrated for the electrohydraulically and electromagnetically generated shock waves systems. The piezoelectric system is especially useful in elderly and frail patients because no general anesthesia is needed and only 14% of cases require analgesia or sedation. PMID- 1612035 TI - Regulation of chorionic gonadotropin-alpha and chorionic somatomammotropin messenger ribonucleic acid expression by 8-bromo-adenosine 3',5'-monophosphate and dexamethasone in cultured rhesus monkey syncytiotrophoblasts. AB - We wished to establish an in vitro culture system to examine gene expression in the context of differentiated function with rhesus monkey syncytiotrophoblasts. Chorionic villous tissue from placentas obtained at cesarean section was dispersed with trypsin and DNase and fractionated on a 5-70% Percoll gradient. When placed in culture, cells from a mononuclear fraction demonstrated to be very highly enriched (95-97% pure) for cytotrophoblasts aggregated and began to form syncytia within 24 h in culture, reminiscent of placental syncytiotrophoblast formation. The migration and fusion of individual cytotrophoblasts to form multinuclear syncytia were documented with time-lapse video microscopy. Incorporation studies with tritiated thymidine supported the conclusion from videomicroscopy that syncytia form by the fusion of individual cells and the addition of mononuclear cells to existing syncytia, rather than by endomitosis. The syncytiotrophoblast marker pregnancy-specific beta 1-glycoprotein (SP1) was immunocytochemically identified in both intact placenta and cultured syncytiotrophoblast cells. With cells isolated from placentas obtained on day 28, 50, 70, or 140 of pregnancy, treatment with 8-bromo-cAMP increased both rhesus monkey CG alpha-subunit (mCG alpha) and chorionic somatomammotropin (mCS) mRNA levels by an average of 4-fold. Increases of up to 2.5-fold were seen with mCG alpha mRNA in as little as 2 h after treatment, with a statistically significant average response seen within 6 h. The response with mCS required at least 24 h before a significant effect was seen. Actin mRNA levels were generally unchanged or suppressed by this treatment, indicating that the effect of 8-bromo-cAMP is relatively specific for the hormone mRNAs. Treatment of syncytiotrophoblasts with dexamethasone, but not progesterone or androstenedione, resulted in an approximately 4-fold increase in mCG alpha mRNA levels within 6 h of treatment. Steroid treatment did not affect mCS mRNA levels. Treatment with 4.5-400 nM GnRH or 0.1 to 100 ng/ml basic fibroblast growth factor likewise had no effect on the level of either mRNA, suggesting that any actions of these factors on hormone secretion are not effected via changes in steady state mRNA. These results communicate that the expression of the mRNAs for rhesus monkey CG alpha and CS in syncytiotrophoblast are regulated by steroid hormone- and cAMP-mediated pathways. PMID- 1612037 TI - Value of endoscopic retrograde cholangiopancreatography in determining the cause but not course of acute pancreatitis. AB - We have recently shown that ERCP is the most useful technique for detecting a biliary origin of acute pancreatitis and can be done without side effects. We now report on a second series of 50 patients with acute pancreatitis in whom ERCP, computed tomography (CT), ultrasound (US), and clinical and laboratory assessment were performed within the first 24 to 48 hours of hospitalization. A score for ERCP, CT and US was used to assess the severity of the disease. Patients were followed up until discharge or death and their condition classified according to outcome as mild (less than or equal to 1 complication), severe (greater than 1 complication) or fatal. ERCP was superior in detecting choledochal stones (ERCP 100%, US 25%, CT 50%) and dilated intrahepatic ducts (ERCP 75%, US 75%, CT 37%) but not gallbladder stones (ERCP 70%, US 100%, CT 60%). When the ERCP severity score was calculated there was no relevant difference between patients thereafter having a mild course (0.66 +/- 0.91, range 0-3), a severe course (1.3 +/- 0.80, range 0-3), or a fatal outcome (1.0 +/- 1.1, range 0-3). In contrast, the CT score was different in all three groups (mild: 3.0 +/- 1.9; severe: 5.3 +/- 3.2; lethal: 6.3 +/- 3.1) as was the US score (mild: 1.5 +/- 1.3; severe: 3.2 +/- 2.3; lethal: 4.4 +/- 1.4). It is concluded from these results that ERCP is of value in defining the origin of acute pancreatitis. When a biliary origin is detected this can lead to immediate treatment using endoscopic sphincterotomy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612039 TI - Endoscopic orientation within the duodenal bulb. AB - Laparotomy performed for bleeding duodenal ulcer after diagnostic/therapeutic endoscopy revealed a disparity in location of the lesion on several occasions at our institution. The position of the duodenal lesion is important in assessing bleeding potential. Twenty consecutive patients underwent upper gastrointestinal endoscopy by a staff and trainee gastroenterologist to evaluate the ability to determine the true posterior position of the duodenal bulb. Documentation of the posterior bulb location was verified by pooled colored fluid with the patient in a supine position. True posterior location was chosen only 30% of the time by an experienced gastroenterologist. This observation may have clinical implications in assessing the patient's bleeding potential and in the use of coaptive coagulation for control of ulcer bleeding. PMID- 1612038 TI - Association of juxtapapillary diverticula with choledocholithiasis but not with cholecystolithiasis. AB - Juxtapapillary diverticula are often associated with biliary lithiasis. The aim of this study was to compare the prevalence of juxtapapillary diverticula in choledocholithiasis and in cholecystolithiasis without common bile duct stones. The results of 520 consecutive retrograde cholangiographies were retrospectively analysed. The prevalence of juxtapapillary diverticula was higher in patients with biliary lithiasis than in patients without: 26.0% vs 10.5% (p less than 0.001). However, juxtapapillary diverticula were more frequently encountered in patients with choledocholithiasis than in those with gallbladder lithiasis or previous cholecystectomy and a stone-free common bile duct: 40.0% vs 10.2% (p less than 0.001). There was no significant difference between the patients with cholecystolithiasis alone and those without biliary lithiasis. Among the patients with previous cholecystectomy or with gallbladder lithiasis, common bile duct stones were more frequently found in patients with juxtapapillary diverticula than in those without: 80.3% vs 40.6% (p less than 0.001). These data suggest that juxtapapillary diverticula are associated only with choledocholithiasis and not with gallbladder lithiasis. PMID- 1612040 TI - Randomized placebo-controlled trial of oral liquid simethicone prior to upper gastrointestinal endoscopy. AB - It has been suggested that pre-procedural oral simethicone improves visibility in upper GI tract endoscopy. We examined three-hundred-thirty patients referred for upper endoscopy who were randomized and were required to swallow a placebo solution or one of three liquid simethicone solutions 15 min prior to the examination. These solutions contained 65 mg, 65 mg and 195 mg of drug dissolved in 90 ml, 30 ml and 90 ml of water, respectively. Patients treated with both dosages of simethicone revealed significantly less foam and bubbles in both the stomach and the duodenum compared to placebo. Only the 90 ml volume adequately cleared both locations. The reduction of examination time could be found both in patients with an intact stomach and in patients with or without gastric bile reflux, but was most striking in patients with previous gastric resection (examination time being reduced by almost 50% and the need of adjunctive lavage being reduced about 20 fold compared to placebo). In conclusion, pre-procedural oral simethicone should be routinely considered in patients with previous gastric resection. The utility of the drug is less evident in patients with normal gastric anatomy. PMID- 1612041 TI - Complications of therapeutic gastrointestinal endoscopy. PMID- 1612042 TI - Complications of endoscopic sclerotherapy of esophageal varices. PMID- 1612043 TI - The importance of determining both urea and ammonium levels in gastric juice for rapid diagnosis of Helicobacter pylori infection. PMID- 1612044 TI - Sentinel polyp and fold: resolution following drug therapy. PMID- 1612045 TI - Chronic anemia due to gastric ectopia within the duodenum. PMID- 1612046 TI - Detection of the fetus at risk. AB - Successful reproduction has ensured the survival of the human race despite disease and famine. However, a good standard of living, combined with a well balanced diet, is closely related to low maternal, perinatal and infant mortality rates. In the third world, anaemia, rheumatic heart disease, tuberculosis and other infections are still common and the poorly nourished are more susceptible to them. In the Western world food is plentiful but often the individual's diet is poorly balanced. Invariably the fetus takes all the nutrients required from the mother and, if a deficiency occurs, this is reflected in the maternal reserves only. The weight of the baby at birth has a wide biological variation and correlates in the extremes with maternal weight but there are many other factors responsible for fetal growth. In early pregnancy the developing embryo may be susceptible to specific dietary deficiencies and structural malformations may result. A clear link has recently been established between folic acid supplementation and the prevention of recurrence of neural tube defects. Excessive doses of vitamin A should be avoided. PMID- 1612047 TI - Is it worthwhile breast-feeding? PMID- 1612048 TI - Which milk for normal infants? PMID- 1612049 TI - After a positive Guthrie--what next? Dietary management for the child with phenylketonuria. PMID- 1612050 TI - Cystic fibrosis--a full-time occupation or more a way of life? PMID- 1612051 TI - The team approach to practical management of childhood diabetes mellitus: a case study. PMID- 1612052 TI - Fats for brains. PMID- 1612053 TI - Alcohol exposure and the fetus. PMID- 1612054 TI - Human characteristics at multi-variable control when the operator changes over the plant-lines. AB - In this paper, we experimentally investigate the human characteristics when the operator changes over the plant-lines. Observing the human behaviour under stable experimental conditions, it was noticed that the time between the change-overs of the controllers is almost constant, that is, the operator seems to change over the controller according to a rhythm (we call it 'rhythmic operation'). Control by rhythmic operation presents two striking differences from that by conventional operation without the rhythm: one is the ability to predict the movement of the controlled quantity exactly, and the other is that there is little differences between cognition and performance. Therefore, we consider a way of calculating the rhythm for the experimental conditions, and attempt to introduce the rhythmic operation over all experimental conditions. As the result of a verification experiment with the rhythmic operation, the control error decreased considerably and the validity for the rhythmic operation was confirmed. Furthermore, we found that the operator's mental workload decreased because the number of indefinite factors involved in the decision making at the change-overs of the controller decreased. PMID- 1612055 TI - An experimental study of pilots' control characteristics for flight of an STOL aircraft in backside of drag curve at approach and landing. AB - In general, most vehicles can be modelled by a multi-variable system which has interactive variables. It can be clearly shown that there is an interactive response in an aircraft's velocity and altitude obtained by stick control and/or throttle control. In particular, if the flight conditions fall to backside of drag curve in the flight of an STOL aircraft at approach and landing then the ratio of drag variation to velocity change has a negative value (delta D/delta u less than 0) and the system of motion presents a non-minimum phase. Therefore, the interaction between velocity and altitude response becomes so complicated that it affects to pilot's control actions and it may be difficult to control the STOL aircraft at approach and landing. In this paper, experimental results of a pilot's ability to control the STOL aircraft are presented for a multi-variable manual control system using a fixed ground base simulator and the pilot's control ability is discussed for the flight of an STOL aircraft at backside of drag curve at approach and landing. PMID- 1612056 TI - An evaluation method of computer usability based on human-to-computer information transmission model. AB - This paper proposes a new evaluation and prediction method for computer usability. This method is based on our two previously proposed information transmission measures created from a human-to-computer information transmission model. The model has three information transmission levels: the device, software, and task content levels. Two measures, called the device independent information measure (DI) and the computer independent information measure (CI), defined on the software and task content levels respectively, are given as the amount of information transmitted. Two information transmission rates are defined as DI/T and CI/T, where T is the task completion time: the device independent information transmission rate (RDI), and the computer independent information transmission rate (RCI). The method utilizes the RDI and RCI rates to evaluate relatively the usability of software and device operations on different computer systems. Experiments using three different systems, in this case a graphical information input task, confirm that the method offers an efficient way of determining computer usability. PMID- 1612057 TI - A method of evaluating VDT screen layout by eye movement analysis. AB - The method for evaluating VDT screen layout by eye movements is studied. When the subjects read from the VDT screen, the change in their line of sight was measured by their eye movements. The measured eye movement patterns were divided into the sequential and rereading processes. When related to these characteristics, the performance of subjects was found to be good when the sequential process predominated over the rereading process. The eye movement pattern was shown to change with screen layout. The eye movement pattern proved effective in determining that tabular format is more legible than textual format. This confirmed the usefulness of the method of evaluating VDT screen layout by the eye movement pattern. PMID- 1612058 TI - Does fatigue exist in a quantitative measurement of eye movements? AB - The measurement system for quantitative analysis of eye movements and distribution of eye fixation points was developed through the study. Experiments on physiological fatigue characteristics of eye movements were studied using the system. The subjects involved in the study were six young males. No significant change was quantitatively found in saccadic eye movements during and/or after five hours of rapid eye tracking tasks. The saccadic velocity of two subjects were found in binocular decreased temporarily. The maximum velocity of eye movements obtained in the present experiment was ascertained in order to produce a scale for various visual work as an ergonomic index. PMID- 1612059 TI - Visual capability to receive character information. Part I: How many characters can we recognize at a glance? AB - A study was made on the capability to receive character information and the factors restricting it. The study showed that the capability indicated by the memory span was limited by the average number of characters for words that are made up of individual characters, and calculated in terms of information quantity, there was no difference among the individual characters. The differences in memory span, depending on the size of the pattern presented, was negligible. The difference in the way characters were arranged produced the difference in memory span saturation. This phenomenon is explained by the nature of the lateral interference effect working among the adjacent characters. PMID- 1612060 TI - Visual capability to receive character information. Part II: How long do we need to memorize the random characters briefly presented? AB - The time-related aspect of the capability to receive character information was measured and analysed. As a result, when the presentation time was shorter than one second, ability was almost constant, but when it exceeded one second it increased as the presentation time increased. It was found that when a pattern was presented without limiting the presentation time, there were linear relationships between the number of characters to be memorized and the time required to memorize all the characters correctly in the range of 2 to 6 characters, 7 to 12 and 13 to 16 (or more). These boundaries corresponded well to a unit of memory well known as the magical number 7 plus minus 2. From these results, it was estimated that a grouping mechanism exists even when memorizing characters and that it has a hierarchical structure. PMID- 1612061 TI - The influence of combined visual and tactile information on finger and eye movements during shape tracing. AB - Adaptation experiments in shape tracing were conducted to investigate finger and eye movements in various conditions of visual and tactile information. Maximum velocity, mean velocity, maximum acceleration and reacceleration point were calculated from finger movements. Number of eye fixations and lead time of eye fixation to finger position were calculated from eye movements. The results showed that for the finger movement the values of the indices studied were higher in the combined visual and tactile condition than in the visual only condition. The number of eye fixations decreased when subjects repeated the tracing and was more marked in the combined visual and tactile condition than in the visual only condition. The results suggest that finger movements become faster and use of vision is reduced when both visual and tactile information are given. PMID- 1612062 TI - Construction of parametric model of operator and workstation. AB - The purpose of development of a parametric model and the construction and formulation of the parametric model are described. To validate the parametric model, the distribution of the difference between the preferred and theoretical seat height settings of a number of office workers was evaluated from the standpoint of the static posture that does not change with time. The results of precise measurements made for an engineering workstation and an operator were also evaluated. Finally, the theoretical seat height settings with dynamic posture were evaluated. The validity of the parametric model was verified under the experimental conditions. PMID- 1612063 TI - Analysis of sitting comfortability of driver's seat by contact shape. AB - In order to evaluate sitting comfort qualitatively, a flexible and very thin sensor was developed to measure the contact shape between a seated man and the seat surface. Each tape has twenty strain gauges on it at regular intervals, and the fourteen tape sensors were arranged on the bottom and back surface of the experimental driver's seat. The contact shapes and postures in thirty two male drivers were measured with two types of seat cushion and sitting posture: free and recommended. Sensory evaluation was made for each experimental condition. The results of the interrelation between the characteristics of the surface deformation, the parameters of body build, sitting posture and feeling of comfort shows that the comfort of each morphological fitting does not correspond to one special and single parameter from those physical factors, but is represented by a function with many parameters related to the deformation, posture and body build. By using these relations, a sensory model for the prediction of the sitting comfort was constructed. PMID- 1612064 TI - The pathogenesis, prediction, and prevention of insulin-dependent diabetes mellitus. AB - The past decade has seen great advances in our understanding of the pathogenesis of IDDM. This knowledge has led to investigate use of a battery of immunologic, genetic, and metabolic tests for identifying people with prediabetes. Therapies designed to arrest autoimmunity have been associated with incomplete responses and the complications of immunosuppression. Ultimately, we hope that IDDM can be eradicated by inducing tolerance to the diabetogenic autoantigen(s). PMID- 1612065 TI - Diabetes mellitus: perspectives on therapy. PMID- 1612066 TI - The rationale for glucose control in diabetes mellitus. AB - After more than 60 years of active investigation, the role of intensive treatment regimens in preventing and ameliorating diabetes complications is close to being resolved. Currently available intensive regimens do not achieve normoglycemia and are associated with significant complications. Moreover, they are dependent on a high level of patient motivation and adherence and may not be widely applicable in the IDDM population. Given these limitations, it is critical that their benefit, if any, be documented before they are introduced widely into clinical therapy. If the glucose hypothesis proves to be true, the benefits of intensive therapy will outweigh all of its limitations. Although previous trials have failed to document benefits with regard to retinopathy (the decrease in the progression from incipient nephropathy to clinical proteinuria is of unknown clinical significance), the DCCT has adequate power to define the role of intensive therapy. If the DCCT demonstrates a salutary effect of intensive therapies, a rationale for such efforts finally will have been established. The goal for the next generation of clinical investigation will be to develop new means of intensive therapy that have less risk and are more accessible and acceptable to all persons with diabetes. PMID- 1612067 TI - Insulin therapy in insulin-dependent (type I) diabetes mellitus. AB - Intensive insulin therapy is suitable for individuals who want optimal glucose control and the least fluctuation in glucose levels. It permits a greater flexibility in life style and the opportunity to vary, within certain limits, meal and exercise schedules and meal content. This therapeutic approach is modeled on physiologic insulin secretion, but shortcomings in the subcutaneous route of delivery hamper the ability to control precisely the glucose levels. The therapy is most successful when the user is motivated to do the glucose monitoring and carbohydrate counting and educated to make rational decisions about how to adjust the insulin doses. PMID- 1612068 TI - Hypoglycemia in the treated diabetic patient. A risk of intensive insulin therapy. AB - With more physiologic insulin replacement and more accurate glucose monitoring, it was believed that very strict glycemic control of IDDM could be achieved without increasing the risks of hypoglycemia. No one anticipated that intensive treatment itself would lead to physiologic adaptations that would impair protective responses and contribute to the two- to threefold increase in risk of hypoglycemia. The influence of diabetes and its control on the recognition of and response to hypoglycemia are explored in this section as well as steps that can be taken by the patient and clinician to reduce these risks. PMID- 1612069 TI - Type II diabetes and syndrome X. Pathogenesis and glycemic management. AB - Non-insulin-dependent diabetes (NIDDM) has long been recognized as being associated with a cluster of disorders including obesity, hypertension, dyslipidemia, and atherosclerotic heart disease. It was only recently, however, that Reaven, DeFronzo, and Ferrannini with techniques to quantitate insulin resistance suggested that this represents a common factor in this group of disorders and that hyperinsulinemia resulting from insulin resistance could be the cause of the hypertension, dyslipidemia, and atherosclerosis. The names syndrome X or the insulin-resistance syndrome have been used to identify this pathological entity, and considerable investigations have been done and are in progress to establish whether or not these coexisting disorders represent an as yet unexplained association of cardiovascular risk factors or if, indeed, insulin resistance and hyperinsulinism represent the primary cause for most of the other disorders. To paraphrase a philosophical comment, if syndrome X did not exist, we probably would have had to invent it. In addition to the intellectual satisfaction of being able to "lump" these diverse ills under a single etiology, the main value of grouping these disorders as a syndrome is to continually remind physicians that the therapeutic goals are not only to correct hyperglycemia in NIDDM but also to manage the elevated blood pressure and dyslipidemia that cause cerebrovascular and cardiac morbidity as well as mortality in these patients. Having a syndrome X reduces the fragmentation of medical care among subspecialties and decreases the likelihood of prescribing drugs that correct hypertension but raise lipids or drugs that lower lipids but raise blood glucose. Finally, it encourages the selection of drugs that reduce hyperglycemia without increasing insulin secretion and to the development of new drugs for this purpose. Unfortunately, the concept of insulin resistance with hyperinsulinism being a cause of the other associated disorders is still unproved but continues to be open to experimental investigation. The remainder of this article reviewed the use of sulfonylureas in the management of NIDDM, discussed new molecular and cellular mechanisms by which they promote insulin secretion, and reviewed the controversy as to whether an extrapancreatic action contributes to their glucose lowering effects in NIDDM. A closing section listed some other oral drugs that can lower blood glucose without stimulating the pancreatic beta cell. Their insulin-sparing hypoglycemic effect makes them potentially useful in NIDDM therapy, particularly if the fundamental premise of syndrome X is substantiated, which implicates hyperinsulinemia as contributing to the morbidity and mortality from atherosclerotic vascular disease. PMID- 1612070 TI - Management of the adult onset diabetic with sulfonylurea drug failure. AB - With apparent failure of SU drug therapy, the management of NIDDM patients becomes even more challenging. The following sequence of actions is recommended. 1. Situational dietary noncompliance (eg, a prolonged vacation or a recent period of family or occupational stress) should be treated first by renewed regular contacts with the dietician. 2. Occult infection, hyperthyroidism, and prescription of hyperglycemic drugs by another physician should be ruled out. 3. If true secondary failure exists, the patient should be started on insulin therapy alone and the program optimized to lower fasting plasma glucose to less than 140 mg/dL (8 mM) and subsequently postprandial glucose levels to less than 200 mg/dL (11 mM). NPH, Lente, or Ultralente insulin given only in the evening may be considered for patients with some indication of preservation of postprandial insulin release. 4. If the patient refuses to accept insulin therapy initially, a temporary switch to another second generation SU drug may be tried, primarily to convince the patient that oral drugs alone are inadequate. 5. If optimized insulin therapy fails to achieve therapeutic goals, if multiple insulin injections are not feasible, or if goals are achieved only at the expense of very large insulin doses, then combination therapy with an SU drug may be tried. PMID- 1612071 TI - Management of hypertension in diabetes. AB - Hypertension should be detected and treated early in diabetic patients. It markedly affects the morbidity and mortality of diabetic individuals as a result of both atherosclerosis and microvascular disease. Antihypertensive treatment is an effective tool in slowing the progression of early and advanced diabetic nephropathy. No prospective studies have addressed the effects of antihypertensive regimens on the incidence of congestive heart failure, stroke, and coronary artery disease in large groups of diabetic patients. Such studies are urgently needed. Special consideration should be given to the effects of antihypertensive drugs on glycemic control and the lipid profile of the diabetic patient. Because hyperinsulinemia (and insulin resistance) have been advocated as hypertensive and atherosclerotic risk factors, the effects of antihypertensive drugs on insulin action and plasma insulin levels may become an important element in the selection an antihypertensive agent. More information, however, is needed in these areas. ACE inhibitors, calcium channel blockers, and alpha-adrenergic blockers probably offer a more favorable metabolic profile as compared with diuretics and beta-blockers. The former agents should be used as initial drugs in most clinical settings. PMID- 1612072 TI - Management of hyperlipidemia in diabetes mellitus. AB - Accelerated atherosclerosis is a major complication of long-term diabetes mellitus, and this is partly due to associated abnormalities of lipoprotein metabolism. Hypertriglyceridemia is usually due to poorly controlled diabetes and responds to improved glucose control. Hypercholesterolemia is usually not related to poor diabetic control and should be treated with a cholesterol lowering diet and drugs according to the National Cholesterol Education Program guidelines. Low HDL-C is common in NIDDM and does not fully return to normal with improved diabetic control. Dyslipidemia in diabetics should be aggressively identified and treated to decrease cardiovascular risk. PMID- 1612073 TI - Diabetic ketoacidosis and hyperosmolar coma. AB - DKA-hyperosmolar coma is a readily diagnosed and easily treated, potentially catastrophic emergency that regularly occurs in both Type I and Type II diabetics. This review emphasized that diabetic ketoacidosis and hyperosmolar coma can, and very frequently do, occur concurrently, but it is the hyperosmolar state rather than the DKA that is the primary cause of coma and death in this condition. One must therefore vigorously treat the hyperosmolarity and resulting dehydration, especially when total calculated osmolarity exceeds 230 to 240 mOsm/L. The major aim of treatment is to rapidly replace the major water loss that is responsible for this clinical condition and to stimulate glucose metabolism with insulin. The diagnosis of this dangerous condition is relatively simple. The therapy, in most regards, is equally apparent. There are good data demonstrating that the prompt recognition of DKA-hyperosmolar coma and the simple institution of rapid rehydration have continued to reduce the mortality and complications of this potentially disastrous complication of diabetes mellitus. PMID- 1612074 TI - Pregnancy in the diabetic woman. Guidelines for a successful outcome. AB - Pregnancy is perceived as a miracle. Many women feel an inner glow and bond to the growing fetus as they change shape, behavior, and attitude. For the sake of the unborn child, women will abstain from alcohol, coffee, and medicine even when they are ravaged by headache and flu. This response to pregnancy is normal and is consistent with the maternal need to protect her young. Women with diabetes are no different from other women in their concern for their fetuses, but they need to work even harder. Even minor deviations from normal glucose values may have a major impact on fetal well-being. The extra work becomes worthwhile with the birth of a healthy infant. PMID- 1612075 TI - Perioperative management of the diabetic patient. AB - The diabetic patient has major surgery more frequently than nondiabetic patients. Although many of these operations are done on an elective basis, desirable perioperative control of blood glucose (ranging from 120-180 mg/dL) remains a therapeutic challenge. In planning the management, the type of diabetes, current treatment, the degree of recent control, the presence of complications, and the type of surgical procedure must all be considered. All insulin-dependent patients and many non-insulin-dependent patients need insulin therapy perioperatively. The variable stress associated with major procedures makes a flexible insulin regimen desirable. This can be provided using a continuous insulin (regular) infusion system and frequent bedside blood glucose monitoring. PMID- 1612076 TI - Organ blood flow and cardiac contractility in anaesthetized cats at 5 bar (500 kPa) ambient pressure. AB - Previous in vivo and in vitro experiments have demonstrated increased cardiac contractility and increased total myocardial blood flow (Qmyocardial) when rats were exposed to normoxic 5-bar (500 kPa) ambient pressure. In the present study, regional blood flow was measured using the microsphere method on nine anaesthetized cats at surface and normoxic 5-bar (500 kPa) ambient pressure. Left ventricular pressure (LVP) and cardiac contractility, measured as peak left ventricular +dP/dt and -dP/dt were measured in six of the cats. Arterial pressure, heart rate and cardiac output remained unchanged after compression, but total Qmyocardial increased by 29% (P less than 0.01) and cerebral blood flow increased by 66% (P less than 0.05). At the same time +dP/dt and -dP/dt was increased by 83% and 102%, respectively (P less than 0.01), while LVP was enhanced by 14% (P less than 0.05). Except for a moderate decrease in partial pressure of oxygen, acid base status in arterial blood remained unchanged. The results indicate that the effects of increased ambient pressure on the heart are general physiological phenomena, which are not only limited to the laboratory rat. PMID- 1612077 TI - Forearm temperature profile during the transient phase of thermal stress. AB - The transient temperature response of the resting human forearm immersed in water at temperatures (Tw) ranging from 15 to 36 degrees C was investigated. Tissue temperature (Tt) was continuously monitored by a calibrated multicouple probe during the 3-h immersions. Tt was measured every 5 mm, from the longitudinal axis of the forearm to the skin surface. Skin temperature, rectal temperature, and blood flow (Q) were also measured during the immersions. The maximum rate of change of the forearm mean tissue temperature (Tt, max) occurred during the first 5 min of the immersion. Tt, max was linearly dependent on Tw (P less than 0.001), with mean values (SEM) ranging from -0.8 (0.1) degrees C.min-1 at 15 degrees C to 0.2 (0.1) degrees C.min-1 at 36 degrees C. The maximum rate of change of compartment mean temperature was dependent (P less than 0.001) on the radial distance from the longitudinal axis of the forearm. The half-time for thermal steady state of the forearm mean tissue temperature was linearly dependent on Tw between 30 and 36 degrees C (P less than 0.01), with mean values (SEM) ranging from 15.6 (0.6) min at 30 degrees C to 9.7 (1.2) min at 36 degrees C and not different between 15 and 30 degrees C, averaging 16.2 (0.6) min. There was a significant linear relationship between the half-time for thermal steady-state of the compartment mean temperature and the radial distance from the longitudinal axis of the forearm for each value of Tw tested (P less than 0.001). The data of the present study suggest that the forearm Q is an important determinant of the transient thermal response of the forearm tissue during thermal stress. PMID- 1612078 TI - Effect of arm-shoulder fatigue on carpenters at work. AB - The purpose of the study was to analyse the effect of arm-shoulder fatigue on manual performance. Ten experienced carpenters performed three standardized tasks (nailing, sawing and screwing). Electromyographic activity was recorded from six arm-shoulder muscles and the performances were video-filmed. After 45 min of standardized arm-cranking (arm-shoulder-fatiguing exercise of approximately 70% 80% maximal oxygen consumption), the tasks were repeated. The number of work movements and the time taken for each task were recorded and the quality of the work performed was compared. After the fatiguing exercise, only nailing was perceived as being harder and more mistakes were made during nailing and sawing. Movement performance was not influenced during nailing but was slightly slower during sawing and faster during screwing. However, there were increased mean EMG amplitudes in the upper trapezius and biceps muscles during nailing, in the upper trapezius, anterior deltoid and infraspinatus muscles during sawing and in the anterior deltoid muscle during screwing. Of the muscles studied the upper trapezius and anterior deltoid muscles increased their activity most after the arm-shoulder-fatiguing exercise. PMID- 1612079 TI - Ventilatory dynamics in children and adults during sinusoidal exercise. AB - The ventilatory response to sinusoidally varying exercise was studied in five adults and seven prepubertal children to determine whether the faster kinetics of ventilation observed in children during abrupt changes in exercise intensity remained more rapid when exercise intensity varied continuously. Each subject exercised on a cycle ergometer first against a constant load and then against a load fluctuating over six different periods ranging from 0.75 to 10 min. The pedal rate was kept constant for all loads. The inspiratory minute ventilation was determined breath-by-breath. Amplitude (A) and phase angle (phi) of the fundamental component and the first harmonics of the ventilatory response were calculated by Fourier analysis for an integer number of waves for each period. From the relationship between A, phi and frequency, dynamic parameters of a first order model with and without delay were compared between adults and children. Firstly we found that the ventilatory time constant was significantly faster in children: 49.7 (SD 9.1) s vs 74.6 (SD 11.1) s (P less than 0.01). Secondly, the change in A and phi with the frequency was not however characteristic of a first order system without delay in most of the subjects (phi greater than 90 degrees for the shorter periods). Thirdly, even when the ventilatory control system was described as a first order model with a positive delay, time constants remained significantly shorter in children: 45.6 (SD 5.7) s vs 67.4 (SD 13) s (P less than 0.01). The ability to increase ventilation faster in children appeared to be a characteristic of the ventilatory control system during exercise independent of the type of drive used. PMID- 1612080 TI - Modelling bivariate relationships when repeated measurements are recorded on more than one subject. AB - This paper examines the problems of modelling bivariate relationships when repeated observations are recorded for each subject. The statistical methods required to test for a common group model were introduced using an example from exercise physiology, where the oxygen cost of running at four different speeds was recorded for a group of 30 recreationally active males. When data for each subject were studied individually, both the plots and correlations suggested the relationship to be linear. Hence, the homogeneity of the subjects' regression lines was compared using the appropriate ANOVA test. The analysis revealed a significant difference in the slopes and intercepts of the lines, thus precluding the use of a single linear model to represent the group. If the subjects were divided into two groups according to the median maximum oxygen consumption (VO2max), a multivariate analysis of variance of the slope and intercept parameters helped to explain some of this heterogeneity (P less than 0.05). However, for physiological rather than statistical reasons, it was necessary to re-analyse the data without the fourth running speed. The revised analysis suggested that the subjects' lines would be better modelled with a common slope but separate intercepts. As before, by dividing the subjects into two groups according to the median VO2max score, a simple t-test indicated that differences in the subjects' intercept parameters were not significant (P = 0.08). Notwithstanding the relatively homogeneous nature of the 30 subjects in terms of VO2max, the statistical methods showed that differences in running economy are, to some extent, dependent on VO2max. PMID- 1612081 TI - The relationship between maximum breath hold time in air and the ventilatory responses to immersion in cold water. AB - Eight subjects performed maximum breath holds in air and naked head-out immersions of 2 min duration in stirred water at 5, 10 and 15 degrees C. Analysis of the respiratory data collected in air and on immersion revealed a significant (P less than 0.05) inverse relationship between the maximum breath hold time (tbh,max) of subjects in air and their frequency of breathing and inspiratory volumes on immersion. No such relationship was identified between tbh,max in air and tidal volumes on immersion. It is concluded that the tbh,max of individuals in air may provide an indication of the magnitude of some of their respiratory responses to immersion. This information may be of use when personnel are being selected for activities with a high risk of immersion in cold water. PMID- 1612082 TI - The effect of prior exercise on oral glucose tolerance in late gestational women. AB - Glucose tolerance deteriorates over the course of a normal human pregnancy as a result of increased peripheral insulin resistance. In contrast, physical exercise has been shown to improve glucose tolerance and blunt the insulin response to a glucose load in insulin-resistant individuals. The purpose of this study was to determine the effect of exercise on glucose tolerance and the insulin response in healthy women during the third trimester of pregnancy (33 weeks of gestation). Five subjects underwent oral glucose tolerance tests (a) 30 min following a 30 min exercise bout on a cycle ergometer at a relative intensity of 50% maximal aerobic capacity, and (b) on a control day without prior exercise. The area under the glucose concentration curve was not different between trials, while the area under the insulin concentration curve was decreased by 23% in the exercise trial compared with the control trial (P less than 0.05). These results suggest that the insulin response to a glucose load is improved in late gestational women by a single bout of moderate intensity exercise. PMID- 1612083 TI - Respiratory sinus arrhythmia alteration following training in endurance athletes. AB - Significant increases in maximum oxygen consumption (VO2max) were noted in nine young track athletes following an 8-week high-intensity running period (P less than 0.05). VO2max was measured, prior to and following the training program, using an on-line, open-circuit spirometry system. Parasympathetic activity was assessed using heart period variation (R-R interval in milliseconds) during carefully controlled breathing activity (R sinus arrhythmia). Following the training program, a 7.3% increase in aerobic capacity was associated with a 23.1% augmentation of efferent parasympathetic activity (P less than 0.01). These data suggest that enhanced aerobic capacity increases efferent parasympathetic tone. PMID- 1612084 TI - Isokinetic rehabilitation after arthroscopic meniscectomy. AB - The aim of this study was to assess the effects in humans of early (2 weeks) and delayed (6 weeks) isokinetic strength training in the recovery of muscle strength following an arthroscopic partial meniscectomy. The peak torque developed in the quadriceps and hamstrings and the torque developed at a knee angle of 1.05 rad were evaluated in 16 subjects, pre-operatively (pre-op), and 2, 6, and 10 weeks post-operatively (post-op), on an isokinetic device at four different velocities (1.05, 2.09, 3.14, and 4.19 rad.s-1). The fatigue characteristics of the muscles were evaluated by having the subject perform 15 maximal contractions at 3.14 rad.s-1. Training was done on the same device (three times a week for 1-2 months), beginning either 2 or 6 weeks post-op. A repeated measures analysis of variance demonstrated a time effect but no differences between groups and no interactions. Torques developed by the knee flexors and extensors were significantly smaller 2 weeks post-op than pre-op, at all velocities tested. Torques developed in the quadriceps recovered to their pre-op values by 6 weeks, and further gained significantly in strength from 6 to 10 weeks. Quadriceps torques remained weaker than the contralateral side at 10 weeks. Hamstrings torques were either higher or similar to pre-op values by 6 weeks, and demonstrated increases from 6 to 10 weeks post-op at 1.05 and 4.19 rad.s-1 only. Total work and average power developed by the quadriceps and hamstrings during the fatigue protocol changed with time in a similar manner to torque.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612085 TI - Erythropoietic adaptations to endurance training. AB - Erythropoietic adaptations involving the oxygen dissociation curve (ODC) and erythropoietin production have been implicated in the etiology of reduced blood haemoglobin concentrations in sportspersons (known as sports anaemia). A significant increase in the half-saturation pressure indicating a right-shift in the ODC was measured in 34 male [25.8-27.4 mmHg (3.44-3.65 kPa)] and 16 female (25.8-27.7 mmHg (3.44-3.69 kPa)] trained distance runners (P less than 0.01 for both genders) after completing a standard 42-km marathon. Erythrocyte 2,3 diphosphoglycerate concentrations measured concurrently were unaltered by exercise, although consistently higher in the female compared to the male athletes (P less than 0.05). The serum erythropoietin (EPO) concentrations of 15 male triathletes (26.3 U.ml-1) were significantly lower than those of 45 male distance runners (31.6 U.ml-1; P less than 0.05). However, the mean serum EPO concentrations of male and female athletes engaged in a variety of sports were not different from those of sedentary control subjects of both sexes (26.5-35.3 U.ml-1). Furthermore, the serum EPO concentrations were unaltered after prolonged strenuous exercise in 20 male marathon runners. These data suggest that the haematological status of these endurance athletes is in fact normal and that the observed shift in the ODC, while providing a physiological advantage during exercise, has no measurable effect on the erythropoietic drive. PMID- 1612086 TI - Influence of the menstrual cycle on the sweating response measured by direct calorimetry in women exposed to warm environmental conditions. AB - The whole body sweating response was measured at rest in eight women during the follicular (F) and the luteal (L) phases of the menstrual cycle. Subjects were exposed for 30-min to neutral (N) environmental conditions [ambient temperature (Ta) 28 degrees C] and then for 90-min to warm (W) environmental conditions (Ta, 35 degrees C) in a direct calorimeter. At the end of the N exposure, tympanic temperature (Tty) was 0.18 (SEM 0.06) degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. During W exposure, the time to the onset of sweating as well as the concomitant increase in body heat content were similar in both phases. At the onset of sweating, the tympanic threshold temperature (Tty,thresh) was higher in the L phase [37.18 (SEM 0.08) degrees C] than in the F phase [36.95 (SEM 0.07) degrees C; P less than 0.01]. The magnitude of the shift in Tty,thresh [0.23 (SEM 0.07) degrees C] was similar to the L-F difference in Tty observed at the end of the N exposure. The mean skin threshold temperature was not statistically different between the two phases. The slope of the relationship between sweating rate and Tty was similar in F and L. It was concluded that the internal set point temperature of resting women exposed to warm environmental conditions shifted to a higher value during the L phase compared to the F phase of the menstrual cycle; and that the magnitude of the shift corresponded to the difference in internal temperature observed in neutral environmental conditions between the two phases. PMID- 1612087 TI - Blood pressure response to low level static contractions. AB - The present study re-examines the 15% MVC concept, i.e. the existence of a circulatory steady-state in low intensity static contractions below 15% of maximal voluntary contraction (MVC). Mean arterial blood pressure was studied during static endurance contractions of the elbow flexor and extensor muscles at forces corresponding to 10% and 40% MVC. Mean value for endurance time at 10% MVC was significantly longer for flexion [111.3 (SD 56.1) min] than for extension [18.1 (SD 7.5) min; n = 7]. At 40% MVC the difference in mean endurance time disappeared [2.3 (SD 0.7) min for elbow flexion and 2.3 (SD 0.7) min for elbow extension]. Mean arterial blood pressure exhibited a continuous and progressive increase during the 10% MVC contractions indicating that the 15% MVC concept would not appear to be valid. The terminal blood pressure value recorded at the point of exhaustion in the 10% MVC elbow extension experiment was identical to the peak pressure attained in the 40% MVC contraction. For the elbow flexors the terminal pressor response was slightly but significantly lower at 10% MVC [122.3 (SD 10.1) mmHg, 16.3 (SD 1.4) kPa] in comparison with 40% MVC [130.4 (SD 7.4) mmHg, 17.4 (SD 1.0) kPa]. When the circulation to the muscles was arrested just prior to the cessation of the contraction, blood pressure only partly recovered and remained elevated for as long as the occlusion persisted, indicating the level of pressure-raising muscle chemoreflexes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612088 TI - Exercise for older women: a training method and its influences on physical and cognitive performance. AB - The decline in physical and mental ability often associated with increasing age in adults has both social and economic implications that affect most nations. Hence, the maintenance of functional capacity and independence of the older person are beneficial both for the individual and society alike. One way to enhance functioning in old age is physical exercise. However, few methods exist that enable older people to monitor and regulate exercise intensity without using expensive apparatus. Utilizing the individual's subjective feeling of perceived exertion through the use of a simple rating scale is an approach that differs markedly from those previously employed. The present study used the ratings of perceived exertion (RPE) scale to induce different exercise intensities in groups of older women. Walking was chosen as the type of exercise since most older women are unfamiliar with, or afraid to engage in, other types of physical exercise such as bicycling or running. Results indicated that physical exercise capacity increased after 3 months of regular low-intensity walking in the exercise groups but not in nonexercising controls. Furthermore, these changes were accompanied by improved digit span performance. In conclusion, this study has shown that the RPE scale may be used for exercise regulation and that older women would seem to be able to use the scale to monitor and regulate their exercise intensity in an outdoor environment in much the same way as younger individuals. PMID- 1612089 TI - A comparison of strength and muscle endurance in strength-trained and untrained women. AB - Muscular strength and fatigability of strength-trained (ST) and untrained (UT) women were compared during a 6-min bout of maximal rhythmic exercise involving the elbow flexor muscles given at a rate of 30 contractions.min-1. Fifteen ST and 15 UT subjects, aged 18-34 years and pair-matched for body size, were tested for differences in initial strength, final strength, absolute endurance, relative endurance, and rate of fatigue. Results revealed a significant difference in initial strength, final strength, and absolute endurance in favor of ST subjects. No significant difference was found for relative endurance, and rates of fatigue were similar for both groups. It is concluded that muscular strength and endurance are enhanced in women engaged in a training program designed primarily to increase muscular strength and hypertrophy, but fatigability is not affected. PMID- 1612090 TI - Temperatures of skin, subcutaneous tissue, muscle and core in resting men in cold, comfortable and hot conditions. AB - To examine the core-shell model of temperature distribution and the possible role of subcutaneous temperature in heat regulation, comprehensive temperature measurements were made on six nude resting men exposed for 2-3 h to comfort (27 degrees C), cold (15 degrees C) and heat (45 degrees C). Cold produced strong shivering and heat caused heavy sweating. Temperatures were recorded every 10 min from: esophagus, rectum and auditory canal; back muscle and thigh muscle at 20 mm and 40 mm depths; 6 subcutaneous sites; and 16 skin sites. Average temperatures at these 29 sites were tabulated at the ends of comfort, hot and cold and the onsets of sweating and shivering. Body temperature changes were slow to develop, the skin temperatures being fastest, and successively deeper tissues progressively slower. There was occasional after-drop and after-rise. The data were consistent with the core-shell concept. The temperature gradient from subcutaneous tissue to skin, which differed substantially with comfort, the onset of shivering and the onset of sweating, could serve as a regulatory signal. The data are now in computer format and may be of interest to biothermal modelers. PMID- 1612091 TI - The energy cost of common tasks in rural Nepal: levels of energy expenditure compatible with sustained physical activity. AB - Three hundred and six measurements of energy expenditure by indirect calorimetry of sitting at rest and self-paced activity were made on 41 men, 48 women and 6 adolescents in a mountain village of Nepal. Except for walking and carrying uphill, measured activities fell within the range of values for light to moderate effort, despite appearing physically demanding. Villagers tended to reduce travel speed when carrying heavy loads (54-102% of body mass on various inclines), averaging a moderate level of energy expenditure which could be sustained throughout the day. Such moderately demanding work was also assumed by pregnant, lactating women and young adolescents. Pregnant women worked more slowly at some tasks, but did not differentiate themselves from their non-pregnant, non lactating counterparts for travel on the mountain side. PMID- 1612092 TI - Syndrome X: radionuclide studies of myocardial perfusion in patients with chest pain and normal coronary arteriograms. PMID- 1612093 TI - Two-step tumour targetting in ovarian cancer patients using biotinylated monoclonal antibodies and radioactive streptavidin. AB - A new method for intraperitoneal tumour targetting in ovarian cancer using biotinylated monoclonal antibodies (MoAb) and radioactive streptavidin is described. Fifteen patients with histologically documented ovarian carcinoma were injected intraperitoneally with 2 mg of biotinylated MoAb MOv18, followed 3-5 days later by 100-150 micrograms of indium-111 streptavidin, at the specific activity of 280-370 MBq/mg in 500 ml of normal saline. No toxicity was observed. Tumours were imaged from 2 to 48 h after radioactivity injection by recording both planar and single photon emission tomography (SPET) data. All patients underwent surgery 1-8 days later (mean 3 days) after scanning. The resected tumour and normal tissue radioactivity were measured. On the day of surgery, the tumour to normal tissue ratio was 9:1 (range 3:1-30:1) and 45:1 (range 12:1 120:1) for intra- and extraperitoneal samples, respectively. The mean tumor to blood ratio was 14:1 (range 4:1-30:1). The injected dose (i.d.) per gram of tumour was 0.112 (range 0.01-0.3) for recurrences and 0.05 for primary tumour (range 0.005-0.2). Over 24-48 h 14% i.d. (range 8-18% i.d.) was found in the urine, 14% i.d. (range 6-29% i.d.) in the blood and 63% i.d. (range 56-70% i.d.) was still in the peritoneal cavity. These preliminary clinical data suggest that this two-step strategy may be superior to the conventional approach (radiolabelled antibodies) for intraperitoneal radioimmunolocalization and radioimmunotherapy of ovarian cancer. PMID- 1612094 TI - Abnormal bone scintigraphy and silent radiography in localized reflex sympathetic dystrophy syndrome. AB - Typical, definite forms of the reflex sympathetic dystrophy syndrome present no diagnostic problems, but the diagnosis of localized or very localized forms is very difficult. In the absence of characteristic roentgenographic evidence of acute, patchy, bony demineralization in the affected extremity, scintigraphy has proven to be a valuable examination. A retrospective analysis of 6 patients with a partial form of reflex sympathetic dystrophy with negative roentgenogram results who were evaluated by bone scintigraphy is presented. In the initial clinical stages, the predominant scintigraphic pattern was a very localized and intense hyperactivity in the internal femoral condyle and/or tibial plate of the affected joint on both blood pool and static images. The increased periarticular activity showed a marked decrease in association with remission of the clinical symptoms. In conclusion, bone scintigraphy was found to be a useful tool in the diagnosis and assessment of the therapeutic response genograms and increased periarticular radionuclide activity on scintigrams in the affected extremity are characteristic findings (Intenzo et al. 1989). Cases of reflex sympathetic dystrophy syndrome involving the hip (Lequesne and Mauger 1982) and the knee (Doury et al. 1987) have been reported, although the diagnosis at these sites is more difficult due to the absence of characteristic external signs. Localized or very localized forms of reflex sympathetic dystrophy (mainly involving the knee) with no radiological abnormalities throughout the course of the disease have been documented (Doury et al. 1979; Doury 1982). In these cases, bone scintigraphs proved to be a valuable examination to confirm the diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612095 TI - Fluorine-18 deoxyglucose PET for assessment of viable myocardium in perfusion defects in 99mTc-MIBI SPET: a comparative study in patients with coronary artery disease. AB - Extent and frequency of viable tissue in myocardial segments yielding a perfusion defect on technetium-99m methoxyisobutylisonitrile (99mTc-MIBI), single photon emission tomography (SPET) at rest was prospectively investigated with 2-18F-2 deoxyglucose (18FDG) positron emission tomography (PET) in 46 patients with chronic coronary artery disease (CAD). Of these, 43 had a history of old myocardial infarction. For comparative visual and quantitative evaluation of identical anatomical slices, PET image files were converted into the SPET file structure and into the same matrix size. SPET and PET images were documented and visually (9 segments/patient) or semiquantitatively evaluated by a target-like polar map. Relative perfusion was expressed in percentage of peak 99mTc-MIBI uptake. Sample 18FDG uptake was related to the 18FDG uptake in the area of such maximal perfusion (18FDG uptake was 100% at the 100% 99mTc-MIBI uptake area). Of 414 segments, 167 (40%) revealed a resting perfusion defect. 18FDG uptake was present in 38 (23%) of the defects, while another 40 (24%) segments yielded 18FDG uptake in the periphery of the defect. When grouped according to the degree of 99mTc-MIBI uptake-reduction (in percentage of peak activity), 80% of severe defects (less than or equal to 30% of peak uptake), 48% of moderate (31%-50% of peak uptake) and 31% of mild (greater than 50% of peak uptake) defects were considered as non-viable on the basis of 18FDG uptake. Complete viability was found in none of the severe defects in contrast to 29% of moderate and 35% of mild perfusion defects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612096 TI - Correlations of left ventricular diastolic parameters and heart rate: assessment through right ventricular pacing. AB - This study evaluated the correlations between left ventricular (LV) diastolic parameters assessed by equilibrium radionuclide angiography (ERNA) and heart rate (HR) through right ventricular pacing. Twelve patients with a permanent right ventricular apex pace-maker were included. Serial ERNA studies were performed under 6 sets of pacing cycle length (heart rate = 52, 62, 72, 82, 92, 104 beats/min) for each patient. The left ventricular ejection fraction was 49.9% +/- 3.1% under pacing HR of 52 bpm and 43.8% +/- 3.1% under pacing HR of 104 bpm. The peak filling rate (PFR) increased very significantly with HR (r = 0.98, P less than 0.001). When the relative changes of end-diastolic volume were taken into account, the correlation between PFR and HR remained significant (r = 0.94, P less than 0.001). The absolute time to PFR (TPFR) did not significantly change with HR, but the ratio of TPFR to cycle length strongly correlated with HR. Our study clearly demonstrates that the PFR assessed by ERNA increases and the TPFR occupies an increasing proportion of the cycle length as HR increases. Therefore, LV diastolic parameters should be normalized for HR in clinical applications. In particular, HR changes should be considered when LV diastolic parameters are used for the assessment of therapeutic interventions. PMID- 1612098 TI - Torticollis nasopharyngealis (Grisel's syndrome). PMID- 1612097 TI - Pulmonary nuclear medicine. AB - This article reviews the contribution made by nuclear imaging to the assessment, diagnosis and monitoring of patients with respiratory disease. It focuses on several specific areas including the diagnosis of pulmonary embolism, the investigation of intrapulmonary infection and neoplasm and the role of positron emission tomography (PET) scanning. PMID- 1612099 TI - Peritoneal mesothelioma: hypertrophic gastroepiploic and omental arteries identified by radioimmune angiography. AB - We report a first case of malignant peritoneal mesothelioma examined by radioimmune (RI) angiography with technetium-99m human serum albumin. The RI angiography clearly demonstrated the characteristic findings including hypertrophic gastroepiploic arteries and dilated omental branches. These findings may be very helpful in distinguishing malignant peritoneal mesotheliomas from peritoneal carcinomatosis. PMID- 1612100 TI - The role of muscarinic M1 and M2 receptors in airway constriction in the cat. AB - The role of prejunctional inhibitory and facilitatory muscarinic receptors was investigated in cats with tracheal hyperresponsiveness to vagal stimulation. Intrathoracic airway caliber (total lung resistance (RL) and dynamic compliance (Cdyn] and the diameter of tracheal ring 4 were measured during vagal stimulation and local acetylcholine (ACh) injection before and after administration of the M1 receptor antagonist pirenzepine or the M2 receptor antagonist gallamine. The responses of tracheal ring 4, RL, and Cdyn to ACh were unaltered by gallamine or pirenzepine. Changes in RL and Cdyn during vagal stimulation were enhanced by gallamine, but the magnitude of tracheal constriction was unchanged. Vagally induced tracheal constriction was decreased by pirenzepine in hyperresponsive but not in control cats. The M2 receptors limit intrathoracic airway constriction, but a functional role for M2 receptors in the cervical trachea could not be demonstrated. However, these data suggest that M1 excitatory receptors may play a role in vagally mediated tracheal hyperreactivity. PMID- 1612101 TI - Time-dependent anticonvulsant activity of melatonin in hamsters. AB - The objective of the present study was to assess whether the anticonvulsant activity of melatonin displays diurnal variability in hamsters. Convulsions were induced by administering 3-mercaptopropionic acid (3-MP). There was a significant diurnal variation in 3-MP-induced convulsions, hamsters being more prone to exhibit seizures during the night than during the day. Melatonin (50 mg/kg i.p.) had a maximal anticonvulsive effect in the early evening (20:00 h). The administration at 20:00 h of the central-type benzodiazepine antagonist, Ro 15 1788, although unable by itself to modify seizure threshold, blunted the anticonvulsant response to melatonin. The results indicate that the time dependent anticonvulsant activity of melatonin is sensitive to central-type benzodiazepine antagonism. PMID- 1612102 TI - Further investigations on the antipropulsive effect of centrally administered histamine and its relation with morphine. AB - The effect of intracerebroventricularly (i.c.v.) administered histamine (100 micrograms/rat) on intestinal myoelectrical activity was investigated in the jejunum of fasted rats. Histamine caused the disappearance of phase III and a partial reduction of phase II of migrating myoelectric complexes. This effect was antagonized by i.c.v. pretreatment with mepyramine (10 micrograms/rat), an H1 receptor antagonist. Lesions of central noradrenergic neurons by i.c.v. injection of the neurotoxin 6-hydroxydopamine strongly reduced both the inhibition of intestinal propulsion and the migrating myoelectric complexes profile induced by i.c.v. histamine, whereas pretreatment with p-chlorophenylalanine, a selective depletor of serotonin stores, had no effect. It thus appears that aminergic pathways are involved in the visceral effects of central histamine. Mepyramine (200 micrograms/rat i.c.v.) partially reduced the slowing of intestinal transit induced by high doses of morphine. Pretreatment with compound 48/80 (10 micrograms/rat i.c.v.), a mast cell degranulator, but not with alpha fluoromethylhistidine, an irreversible inhibitor of histidine decarboxylase, reduced the antipropulsive action of i.c.v. morphine to the same extent as mepyramine, suggesting that histamine released from cerebral mast cells by high doses of morphine could contribute to the intestinal inhibition by morphine. PMID- 1612103 TI - Mexiletine's antifibrillatory actions are limited by the occurrence of convulsions in conscious animals. AB - The antiarrhythmic actions of the racemate and enantiomers of mexiletine were studied in conscious and anaesthetised rats. Racemate or enantiomers, at 20 mg/kg i.v., had little effect on ischaemia-induced ventricular fibrillation in conscious or anaesthetised rats. In conscious rats 20 mg/kg caused convulsions in 78-89% of rats when the plasma concentration of racemate was 20 +/- 2 microM. In anaesthetized animals a higher dose (40 mg/kg) of racemate could be given; this completely prevented ischaemia-induced fibrillation when the plasma concentration was 26 +/- 2 microM. Racemate and enantiomers accumulated in the heart and brain of conscious animals to give tissue: plasma ratios of 7.5 and 23, respectively. With electrical stimulation, both racemate and enantiomers dose dependently (4-32 mg/kg) increased threshold currents for induction of ventricular fibrillation, increased refractory period and minimally changed the ECG; findings expected with a Class Ib antiarrhythmic. The above studies failed to show major differences between racemate or enantiomers except for consistently lower (20-30%) plasma concentrations of R(-) at all dose levels. In conclusion, mexiletine prevented ischaemia-induced ventricular fibrillation in anaesthetised animals but only when given at doses producing convulsions in conscious animals. PMID- 1612104 TI - Comparison of the effects of buspirone and chlordiazepoxide on differential reinforcement of low rates of response. AB - Buspirone is a novel agent which is clinically effective as an anxiolytic but which lacks the muscle relaxant, anticonvulsant and sedative effects of classical anxiolytics. It also lacks the full spectrum of action of classical anxiolytics in animal models of anxiety based on shock and novelty. In the present paper the effects of buspirone and chlordiazepoxide were tested on acquisition of differential reinforcement of low rates of response (DRL). This schedule involves the suppression of behaviour by reward omission and has shown consistent effects with classical anxiolytics. Buspirone was tested at doses of 0.3, 1.1 and 3.3 mg/kg i.p. and chlordiazepoxide at 5 and 20 mg/kg. Buspirone produced effects similar to those of chlordiazepoxide on accuracy of DRL responding. However, the size of the observed effects of buspirone was small even in relation to the 5 mg/kg dose of chlordiazepoxide and did not appear to be directly related to dose. Chlordiazepoxide increased overall rate of responding, while buspirone decreased it. Buspirone appears to show only limited conformity with benzodiazepines in animal models of anxiety and this result appears independent of the reinforcer used in the task. PMID- 1612105 TI - L-canavanine selectively augments contraction in aortas from endotoxemic rats. AB - Contractile responses to KCl or phenylephrine were inhibited in endothelium denuded aorta from endotoxin-treated rats. L-Canavanine, a selective inhibitor of inducible nitric oxide synthase, augmented contractile responses in vessels from endotoxin, but not saline-pretreated animals. In contrast to nitroarginine, L canavanine did not inhibit endothelium-dependent relaxation induced by acetylcholine. Selective inhibitors of inducible nitric oxide synthase may be useful probes of vascular dysfunction in sepsis. PMID- 1612106 TI - Feeding pattern studies suggest that d-fenfluramine and sertraline specifically enhance the state of satiety in rats. AB - The effects of d-fenfluramine (1.5 mg/kg) and sertraline (10 mg/kg), administered intraperitoneally once daily for seven days were studied on feeding parameters of rats over various periods. On the first day of treatment both drugs markedly reduced meal size and meal duration during the first hour and, to a lesser extent, the first 4 h. No effects were seen later. The size and duration of eating bouts were also markedly reduced by both drugs in the first hour. There was no significant effect of either drug on meal frequency in any period. Only d fenfluramine significantly reduced the rate of eating within 4 h from the start of testing. Sertraline, but not d-fenfluramine, markedly increased locomotor activity in the first 4 h after the start of testing. The d-fenfluramine effect on eating rate disappeared by the second day whereas total intake and meal size were still reduced on day five. By days six and seven however the d-fenfluramine treated rats did not differ from the controls. During the seven-day treatment sertraline always reduced total food eaten and meal size but caused only transient changes of locomotor activity and eating rate. Since the effects of d fenfluramine and sertraline on meal size and food intake could be separated from the effects on eating rate and arousal, it appears that at appropriate doses these drugs specifically increase the satiating effect of food. Tolerance to this effect appears to develop more rapidly for d-fenfluramine than for sertraline. PMID- 1612107 TI - Effect of mebeverine hydrochloride on jejunal motility and epithelial transport in the anesthetized ferret. AB - Previous in vitro and in vivo studies demonstrate that mebeverine, administered to isolated smooth muscle preparations or given intravenously, (i.v.), acts as an antispasmodic agent and may be useful in treating intestinal hypermotility. Whether mebeverine affects intestinal mucosal transport is, however, unknown. The aim of the present study was to characterize the effect of mebeverine on both small intestinal motor activity and electrogenic epithelial transport in the urethane anesthetized ferret. The effects of mebeverine were compared following i.v. and intrajejunal (i.j.) administration. Following both routes of drug administration mebeverine dose dependently inhibited jejunal motility, with the i.j. route being more potent. However, when administered i.v. but not i.j., the doses of mebeverine that inhibited jejunal motility also significantly reduced heart rate and arterial blood pressure. Mebeverine (0.1-10 mg/kg) administered i.v. had no significant effect on epithelial transport as measured by a change in transmural potential difference. However, when dosed i.j., mebeverine (0.1-10 mg/kg) induced a decrease in potential difference towards lower lumen negativity, which was suggestive of a decrease in fluid secretion or enhancement of absorption. In conclusion, the results confirm in vivo the antispasmodic effect of mebeverine and suggested that mebeverine can influence epithelial transport, probably in the direction of enhanced intestinal absorption. PMID- 1612108 TI - Modulation of acute inflammation by endogenous nitric oxide. AB - The role of endogenous nitric oxide (NO) in acute inflammation was investigated using two inhibitors of NO synthase (NG-nitro-L-arginine methyl ester(L-NAME) and NG-monomethyl-L-arginine (L-NMMA)) as well as L- or D-arginine. The effect of test compounds was studied on the carrageenin-induced increase in vascular permeability in rat skin and in dextran- and carrageenin-induced paw oedema. Both L-NAME and L-NMMA dose dependently inhibited the increase in vascular permeability and oedema formation. L- but not D-arginine increased these inflammatory responses and reversed the inhibitory effects of L-NAME and L-NMMA. In dexamethasone-treated rats L-arginine enhanced the dextran-induced oedema and the early phase of carrageenin-induced oedema but did not modify the inhibition by dexamethasone of the late phase of carrageenin-induced oedema. These results suggest that endogenous NO is released at the site of acute inflammation and modulates oedema formation. Depending on the time course or on the type of inflammation, NO may be predominantly generated by the constitutive or by the inducible NO synthase. PMID- 1612109 TI - Cholecystokinin contracts isolated human and monkey iris sphincters; a study with CCK receptor antagonists. AB - The contractile effects of cholecystokinin (CCK) on iris sphincter and ciliary muscles from monkey and human eyes were studied using an isolated smooth muscle bath. The ability of the CCKA receptor antagonists, lorglumide and loxiglumide, to inhibit CCK-8s-induced contraction was also examined. Various neuropeptides reported to be present in capsaicin-sensitive sensory neurons were also screened for contractile effect. CCK contracted isolated human and monkey iris sphincters at nM concentrations. Both antagonists caused a rightward shift of the dose response curve for CCK-8s on the monkey iris sphincter. The ciliary muscle from both species failed to contract in response to CCK-8s. Of the eight other neuropeptides screened on the monkey iris sphincter, only [Arg8]vasopressin elicited a weak contraction when used in microM concentrations. These results indicate that the primate iridial sphincter muscle exhibits a high sensitivity to CCK, and that CCKA receptor antagonists effectively block the CCK-induced contraction. PMID- 1612110 TI - Smooth muscle relaxation and inhibition of responses to pinacidil and cromakalim induced by phentolamine in guinea-pig isolated trachea. AB - A concentration-dependent relaxant effect of phentolamine was demonstrated in guinea-pig isolated trachea and was probably unrelated to its alpha-adrenoceptor blocking action. The maximal effect of phentolamine against spontaneous tracheal tone was in the 24-100% range. However, phentolamine produced 100% relaxation when the tone was induced by histamine, carbachol, 30 mM K+ or 124 mM K+. Relaxant EC50 values ranged from 8 to 50 microM with the highest potency found against histamine-induced contractions. Phentolamine caused no suppression of contractions elicited by prostaglandin F2 alpha (PGF2 alpha) or leukotriene C4 (LTC4). At a concentration of 100 microM the alpha 2-adrenoceptor blocker, yohimbine, produced minor inhibition of spasmogen-induced tone, whereas the alpha 1-adrenoceptor blocker prazosin (up to 10 microM) had no inhibitory effects in the trachealis. Propranolol (1 microM), prazosin (1 microM), yohimbine (100 microM), tetrodotoxin (3 microM), glibenclamide (10 microM), tetraethylammonium (8 mM), 4-aminopyridine (5 mM), procaine (100 microM), dipyridamole (3 microM) or methylene blue (100 microM) did not influence the relaxant responses to phentolamine. In tracheal preparations contracted by PGF2 alpha or LTC4, phentolamine (1, 10 and 100 microM) antagonized the relaxant action of the K+ channel openers, pinacidil and cromakalim. The concentration-relaxation curves for pinacidil were shifted 30-fold to the right without change in the maximal effects, whereas the maximal cromakalim-induced relaxant responses were markedly suppressed by phentolamine. PMID- 1612111 TI - L-arginine induces relaxation of small mesenteric arteries from endotoxin-treated rats. AB - The effect of arginine (Arg) was studied on norepinephrine- (1 microM) precontracted small mesenteric arteries removed from rats treated with E. coli lipopolysaccharide (LPS). The addition of L- (but not D-) Arg (1 mM) relaxed, within 3 min, the small mesenteric arteries from LPS-treated but not from control rats, the maximal relaxation (65.3 +/- 11%) being reached with less than 100 microM L-Arg. NG-Nitro-L-arginine methyl ester (1 mM) and methylene blue (10 microM) restored contractions to the level reached before addition of L-Arg. These results show that LPS induces the production of an L-Arg-derived, nitric oxide-like, relaxing factor in small mesenteric arteries. PMID- 1612112 TI - Neuraminidase reduces the number of super-high-affinity [3H]oxotremorine-M binding sites in lung. AB - The effects of neuraminidase on the binding of the radioligand agonist [3H]oxotremorine-M ([3H]oxo-M) were investigated in lung membranes. [3H]Oxo-M labelled super-high-affinity binding sites (KD of 1.36 nM), as indicated by the very high affinity displayed by carbachol when tested in competition with 0.5 mM [3H]oxo-M. Neuraminidase reduced the number of [3H]oxo-M binding sites with no change occurring in the KD. These results suggest that the effects of neuraminidase may explain virus-induced airway hyperresponsiveness. PMID- 1612113 TI - Role of nitric oxide and prostaglandins in sucralfate-induced gastroprotection. AB - We investigated the role of nitric oxide (NO) and prostaglandins (PG) in the prevention by sucralfate of ethanol-induced gastric damage and the decrease of gastric blood flow and compared them with those obtained with nocloprost, a potent locally acting gastroprotective agent. Sucralfate and nocloprost given intragastrically (i.g.) protected dose dependently the gastric mucosa against the damage by absolute ethanol and prevented the decrease in blood flow induced by ethanol. Pretreatment with NG-nitro-L-arginine (L-NNA), an inhibitor of NO synthase decreased dose dependently the protection and the maintenance of blood flow provided by sucralfate but not by nocloprost. This decrease of sucralfate protection was antagonized by L-arginine but not D-arginine. Pretreatment with indomethacin also reversed, in part, the protective and hyperemic effects of sucralfate but the combination of both indomethacin and L-NNA completely abolished these effects. We conclude that sucralfate activates both the NO and PG systems that cooperate in the gastroprotective action of this drug and that NO is not involved in the protection induced by a PGE2 analog. PMID- 1612114 TI - Species-specific recognition patterns of monoclonal antibodies directed against vimentin. AB - Two commercially available monoclonal antibodies raised against the intermediate filament protein vimentin were characterized concerning their species-specific reaction pattern on vertebrate cells. The antibody V9 exhibited extensive reactivity with vimentin of all mammalian species tested, but specifically did not detect vimentin in mouse cells and chicken fibroblasts. The antibody VIM 3B4 recognized vimentin in cells of chicken and most mammalian species, except for rodent species. Characterization of the binding site of VIM 3B4 on human vimentin by limited proteolysis and immunoblotting as well as by sequence comparison strongly suggested that the epitope is located in the coil 2 part of the vimentin rod domain. Site-directed mutagenesis of a mouse vimentin cDNA clone followed by in vivo expression showed that VIM 3B4 could detect rodent vimentin containing a single amino acid substitution (valine for leucine) at position 353 of the mouse vimentin sequence. Practical application for this finding was demonstrated by the unequivocal identification of a modified murine vimentin protein, distinct from the endogenous vimentin, in a cytoplasmic intermediate filament network in mouse skin fibroblasts transfected with a recombinant plasmid expression vector. PMID- 1612115 TI - High sensitivity of cultured human trophoblasts to ribosome-inactivating proteins. AB - Many plant proteins possessing abortifacient activities were identified as ribosome-inactivating proteins (RIPs). The effect of several ribosome inactivating proteins (saporin 6, dianthin 32, pokeweed antiviral protein from seeds, gelonin, bryodin-R, and momordin) on primary cultures of human trophoblasts and human embryonal fibroblasts and on choriocarcinoma (JAR and BeWo) and ovarian carcinoma (TG) cell lines was studied. Protein synthesis of human trophoblasts and BeWo cells was lowered by RIPs more than that of other cells. The trophoblastic receptors for estradiol were not affected by treatment of the cells with momordin. The binding and uptake of saporin 6 and momordin by BeWo and HeLa cells were not correlated to cell toxicity. PMID- 1612116 TI - Effects of estrogen, epidermal growth factor, and transforming growth factor alpha on the growth of human breast epithelial cells in primary culture. AB - Since 17 beta-estradiol (E2)-stimulated growth in human breast cancer cell lines has been shown to be accompanied by increased production of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) and their receptor, we investigated the effects of E2 and these growth factors on the growth of human breast epithelial cells (HBEC) in primary culture. HBEC from normal, benign, and malignant tissues were cultured in serum-free medium [DME:F12(1:1), 5 mg/ml BSA, 10 ng/ml cholera toxin, 0.5 micrograms/ml cortisol, 10 micrograms/ml insulin] in the presence and absence of E2, EGF, and TGF-alpha. Tritiated-thymidine ([3H]TdR) incorporation into DNA was used as a measure of cell growth. E2 did not stimulate growth of any of the cultures at all concentrations examined (10(-9) to 10(-6) M). In contrast, EGF ranging from 1 to 100 ng/ml consistently increased the growth of cells of all three breast tissue types in a dose-dependent manner. The EGF stimulation was inhibited by MAb 528, a monoclonal antibody against the EGF receptor. TGF-alpha was equally or more effective in stimulating proliferation, although its dose-response range was different than that of EGF. E2 and EGF together acted in a synergistic manner in 50% of the samples examined. These studies suggest that E2 can exert effects on HBEC growth via modulation of the cells' response to EGF. PMID- 1612117 TI - Transforming growth factor beta 1-specific binding proteins on human vascular endothelial cells. AB - Transforming growth factor beta (TGF beta) regulates the growth of human umbilical vein endothelial cells (HUVEC) differently depending on the isoform of TGF beta and the culture conditions. The cells are resistant to growth inhibition by TGF beta when the cells are cultured on substratum coated with gelatin. However, the proliferation of HUVEC cultured on substratum without a gelatin coating is inhibited by TGF beta, depending on the isoform and concentration of TGF beta. Binding assays with 125I-TGF beta 1 reveal that HUVEC contain a single class of high-affinity (Kd = 4.4 pM) TGF beta 1 binding sites with 8500 sites per cell. Affinity cross-linking studies demonstrate that HUVEC express 180 and 80 kDa TGF beta 1 binding sites that do not bind TGF beta 2. The reduction and the removal of glycosaminoglycans does not affect the electrophoretic mobility of the 180-kDa binding protein cross-linked with 125I-TGF beta 1. Therefore, the 180-kDa TGF beta 1 binding protein is not related to the type III TGF beta receptor, but might be a novel TGF beta 1-specific receptor/binding protein expressed on vascular endothelial cells. The expression of TGF beta 1 binding sites is not affected by the presence or absence of the gelatin coating on the culture substratum. The data suggest that a gelatin coating does not regulate the susceptibility of HUVEC to TGF beta 1 at the level of the receptor/binding proteins, and that growth inhibition of HUVEC by TGF beta 1 is linked to the regulation of extracellular matrices required for the interaction between the cells and the substratum. PMID- 1612118 TI - Cell shape changes during transition of basal keratinocytes to mature enucleate cornified envelopes: modulation of terminal differentiation by fibronectin. AB - Normal human keratinocytes (NHK) in submerged culture were used to assess mechanisms associated with in vitro exposure to known stimulators (sodium butyrate; NaB) and inhibitors (fibronectin; FN) of NHK maturation. A multiparameter approach was used to define cell types generated under a range of growth conditions. Differentiation induced in response to NaB occurred through a series of morphologically distinct phenotypes and culminated in the formation of enucleate-cornified envelopes. Two-dimensional electrophoresis provided a limited database to evaluate global changes in cellular protein composition as a function of induced differentiation. Proteins were identified that characterized predominantly basal cell cultures, NaB-treated cells, and fully differentiated NHKs. Growth of NHKs on FN suppressed both spontaneous and NaB-directed maturation and inhibited maximal expression of protein changes associated with the differentiated state. Thus, the composition of the extracellular matrix can modulate (at both the morphologic and protein levels) the response of basal NHKs to a potent differentiation-inducing agent. Abrogation of NHK maturation by FN was not due to adverse effects on cellular metabolism, abortive differentiation, or altered timing of induced differentiation. FN appears to exert its suppressive effect by either maintaining an early stem cell phenotype which is poorly competent for terminal maturation or attenuating an as yet unknown aspect of the NaB-initiated differentiation cascade. PMID- 1612119 TI - Monoclonal antibodies against laminin A chain fragment E3 and their effects on binding to cells and proteoglycan and on kidney development. AB - Rat monoclonal antibodies were raised against fragment E3 of the mouse Engelbreth Holm-Swarm (EHS) tumor laminin and selected according to their exclusive reaction with laminin A chain by immunoblotting and staining pattern in embryonic kidneys by immunofluorescence. Immunochemical studies of nine purified antibodies showed a comparable reaction with unfragmented laminin and fragment E3 but no cross reaction with several other, unrelated laminin fragments including the major cell binding fragment E8. Reduction or pepsin digestion of fragment E3 reduced or abolished antibody binding indicating that most of the epitopes involved are conformation dependent and do not include carbohydrates. They are, however, not identical as shown by different reactivities after proteolytic or chemical cleavage of E3. Four of the antibodies were highly active in inhibiting cell adhesion of the teratocarcinoma cell line F9 and the Schwannoma cell line RN22 on fragment E3 (IC50 approximately 1 microgram/ml), while the others were distinctly less active. No inhibition was observed for cell adhesion on unfragmented laminin, consistent with previous findings that this is largely mediated by binding of fragment E8 to alpha 6 beta 1 integrin. A distinct correlation was observed between cell adhesion inhibition and the inhibition of heparansulfate proteoglycan and heparin binding to fragment E3. Since heparin is not very efficient in inhibiting cell adhesion, it indicates that heparin- and cell binding sites on fragment E3 are in close proximity but not identical. Two of the antibodies also showed partial inhibition of kidney tubule formation in organ culture of embryonic kidney mesenchyme while the other antibodies were inactive. It suggests some but probably minor involvement of the fragment E3 structure of laminin in this developmental process. PMID- 1612120 TI - Skin fibroblasts from aged Fischer 344 rats undergo similar changes in replicative life span but not immortalization with caloric restriction of donors. AB - We have compared the in vitro replicative life span and characteristics of immortalization of skin fibroblast cultures derived from ad libitum-fed and caloric-restricted Fischer 344 rats of 6, 24, and 29 months of age. Cells from all 6-, 24-, and 29-month-old animals showed a gradual decline in proliferative potential as evidenced by decreases in harvest density, in the fraction of cells initiating DNA synthesis, and in the number of population doublings per passage. These declines were accompanied by morphological changes including cell enlargement. The replicative life span prior to immortalization decreased significantly with donor age (P less than 0.0001), while caloric restriction had no effect on the cumulative population doubling level. Prior to immortalization mitotic cells from all cultures showed a normal rat karyotype. Postcrisis cultures tended to have more polyploid cells but there were no characteristic or specific chromosomal changes found in the cells with an immortalized phenotype. Interestingly, fibroblasts derived from caloric-restricted animals had a significantly slower growth rate through the tenth week after immortalization (P less than 0.005). When these cultures were seeded at one-quarter the normal seeding density, to favor the outgrowth of the fastest growing cells, a population with a more "transformed" phenotype emerged. PMID- 1612121 TI - Internalization, lysosomal degradation and new synthesis of surface membrane CD4 in phorbol ester-activated T-lymphocytes and U-937 cells. AB - Protein kinase C activating phorbol esters downregulated membrane CD4 by endocytosis in U-937 and human T-cells. Half-time for internalization (approximately 15 min at 50 ng/ml PMA) was determined by FACS. CD4-bound 125I labeled anti-CD4 mAb was rapidly degraded in PMA-activated cells, whereas degradation was low in resting cells. Endocytosis and/or degradation of anti-CD4 mAb was suppressed by H7, and by inhibitors of membrane traffic (Monensin) and lysosome function (methylamine, chloroquine). Immunocytochemistry localized CD4 to the surface of unstimulated T-cells. Upon PMA stimulation occasional labeling was seen in endosomes but whole cell CD4 decreased dramatically. However, methylamine-treated PMA blasts showed accumulation of CD4 in lysosomes and accordingly, pulse-chase experiments in biolabeled cell cultures suggested a manifest reduction of CD4 half-life in response to PMA. Despite their low surface CD4 density, PMA blasts exhibited uptake and accelerated degradation of anti-CD4 mAb. Also, inhibitors of protein synthesis enhanced the PMA-induced downregulation, and membrane CD4 reappeared on fully activated as well as unstimulated cells treated with trypsin. Ongoing CD4 synthesis in activated cells was further evidenced by metabolic labeling and Northern blot analysis demonstrating unaltered or slightly increased CD4 protein and mRNA levels resulting from PMA. Our findings demonstrate that phorbol esters downregulate the cellular CD4 pool by endocytosis and subsequent lysosomal degradation of membrane CD4. Transport of CD4 to the cell surface and CD4 synthesis is unaffected by activation. PMID- 1612122 TI - Membrane-associated chondroitin sulfate proteoglycan and fibronectin mediate the binding of hemopoietic progenitor cells to stromal cells. AB - The initial step in hemopoiesis is the binding of progenitor cells to stroma. What mediates this binding at the molecular level is not entirely clear. We have previously reported that the cell line FDCP-1, a factor-dependent hemopoietic progenitor cell, actively synthesizes a membrane-associated chondroitin sulfate (CS) proteoglycan (MA-PG) which is unstable. After the binding of the progenitor cell to stromal, the stability of the MA-PG is enhanced, suggesting its involvement in the binding of progenitor cells to the stroma. Since stromal cells possess pericellular fibronectin (FN), we examined the possibility that binding to stromal cells may involve interactions between MA-PG of FDCP-1 on the one side and pericellular FN in stromal cells on the other side. To examine this hypothesis, we developed a cell adherence assay to measure the binding of FDCP-1 cells to a monolayer of stromal cells or to FN-coated dishes. Cell binding was inhibited by a monoclonal antibody against CS as well as by free CS and heparin, suggesting the involvement of MA-PG in the binding. Pretreatment of FDCP-1 cells with chondroitinase ABC, which selectively removes the CS portion of the MA-PG, also affects binding to the stromal cells. The binding was also inhibited by a pentapeptide (GRGDS) which competes with the cell-binding domain of FN as well as by a monoclonal antibody anti-FN. We conclude that interactions between MA-PG and a putative integrin-like molecule in FDCP-1 and the heparin and the cell binding domains in pericellular FN in the stromal cells contribute to the stabilization of progenitor-stromal cell binding which originally comes about by homing receptors of progenitor cells. PMID- 1612123 TI - Thrombin enhances degradation of heparan sulfate in the extracellular matrix by tumor cell heparanase. AB - The ability of normal and malignant blood-borne cells to extravasate correlates with the activity of an endo-beta-D-glucuronidase (heparanase) which degrades heparan sulfate (HS) in the subendothelial extracellular matrix (ECM). The association of malignancy with different types of coagulopathies prompted us to study the effect of thrombin (EC 3.4.21.5), a serine protease elaborated during activation of the clotting cascade, on the ability of heparanase to degrade the ECM-HS. The circulating zymogen form of thrombin, prothrombin, was converted to proteolytically active thrombin during incubation with ECM. Thrombin generation by the ECM was time and dose dependent, reaching maximal conversion by 6 h incubation at 3 U/ml of prothrombin. Heparanase-mediated release of low Mr HS cleavage products from sulfate-labeled ECM was stimulated four- to sixfold in the presence of alpha-thrombin, but there was no effect on degradation of soluble HS. Similar results were obtained with heparanase preparations derived from mouse lymphoma and human hepatoma cell lines and from human placenta. Incubation of ECM with alpha-thrombin alone resulted in release of nearly intact high-Mr labeled proteoglycans. Thrombin stimulation of heparanase action was dose and time dependent, reaching a maximal value at 24 h incubation with 1 microM alpha thrombin. The effect of modified thrombin preparations correlated with their proteolytic activity. Catalytically blocked preparations of thrombin (e.g., DIP alpha-thrombin, MeSO2-alpha-thrombin) failed to facilitate heparanase action, while catalytically modified preparations (e.g., gamma-thrombin, NO2-alpha thrombin) exerted only a slight enhancement. Antithrombin III (ATIII) and hirudin both inhibited thrombin-stimulated heparanase degradation of ECM-bound HS. Heparanase action was also facilitated by ECM-immobilized thrombin to an extent which was similar to that induced by soluble thrombin. This result implies that thrombin sequestered by the subendothelial ECM and protected from interaction with its natural inhibitor ATIII (Bar-Shavit et al., 1989, J. Clin. Invest. 84, 1096-1104) may participate locally in cellular invasion during tumor metastasis, inflammation, and autoimmunity. PMID- 1612124 TI - Temporal correlation between the appearance of testis-specific DNA-binding proteins and the onset of transcription of the testis-specific histone H1t gene. AB - The histone H1t gene is transcribed only in testis. Northern blot analyses reveal that transcription of the H1t gene occurs first in pachytene primary spermatocytes. Thus, there is a temporal correlation between onset of transcription of the gene and synthesis of histone H1t in primary spermatocytes during spermatogenesis. Previous studies revealed that replacement of most H1t and core histones occurs during the midspermatid stage of spermiogenesis by transition proteins TP1 and TP2. In this paper we extend our study of the specific binding of testis nuclear proteins to a unique sequence element within the H1t promoter. The relatively tight binding is competed with an excess of homologous DNA but not with a mutated element. Testis proteins from prepubertal animals do not bind to the 18-bp promoter element out proteins from enriched populations of primary spermatocytes do bind. Therefore, the temporal correlation between onset of transcription of the H1t gene and the time when the specific H1t promoter-binding proteins are detected in primary spermatocytes suggests that the DNA-binding proteins might be germinal cell-specific transcription factors that participate in formation of an active H1t transcription initiation complex. These studies present the first analysis of binding sites for testis nuclear proteins from primary spermatocytes within the promoter of a gene expressed only during this stage of spermatogenesis. PMID- 1612125 TI - Mammary epithelial reorganization on extracellular matrix is mediated by cell surface galactosyltransferase. AB - When plated at appropriate densities in serum-free media, the COMMA-D mammary epithelial cell line rapidly reorganizes into multicellular spheres on the basement membrane matrix derived from Engelbreth-Holm-Swarm murine tumor. Using time-lapse video-microscopy, four stages of reorganization were discerned during the first 24 h of culture. In the first few hours, cells attached to the matrix, elongated, migrated, and formed chains. In the next 6 h, chains of cells linked together in anastomosing networks. In the period between 8 and 18 h postplating, the networks contracted, resulting in dense cords radiating from central aggregates. During the final 6 h, the cords were drawn into the aggregates, which condensed further into spheres. The events occurring during mammary epithelial cell reorganization on the matrix were shown to be mediated by cell surface beta 1,4-galactosyltransferase (GalTase), a receptor that binds N-acetylglucosamine residues on glycosylated proteins. GalTase activity was evident at the surface of cells cultured on reconstituted matrix for 3 h but was absent from cells on glass. The protein alpha-lactalbumin (alpha-LA) inhibits the association of GalTase with N-acetylglucosamine. alpha-LA present from the beginning of culture on reconstituted matrix had no effect on cell attachment but caused concentration dependent inhibition of the first two steps of reorganization, i.e., cell elongation and network formation, which then interfered with subsequent events. These observations were replicated using polyclonal antibodies to GalTase. Reorganization was impaired when alpha-LA was added during the first two stages but no effect was observed when it was added during the last two stages. Cells cultured on plastic, which lack surface GalTase activity, were unperturbed by incubation with alpha-LA. Thus certain events (cell elongation and network elaboration) during mammary epithelial cell reorganization on reconstituted matrix are GalTase dependent, while others (attachment, network contraction, and compaction) are not. The functional and temporal specificity of GalTase involvement indicates that GalTase mediates cell-matrix, but not cell-cell, interactions during epithelial morphogenetic events in culture. PMID- 1612126 TI - Involvement of microtubules and microfilaments in centrosome dynamics during the syncytial mitoses of the early Drosophila embryo. AB - To examine the role of microfilaments and microtubules in centrosome dynamics we exposed Drosophila embryos to culture medium containing cytochalasin B and to low temperature. The results show that the splitting of the centrosomal material does not occur when the embryos are treated with cytochalasin before centrosome duplication at late telophase. The fragmentation of the centrosomal material, caused by cold exposure, is also prevented by cytochalasin incubation. These results indicate that both microtubules and microfilaments may be involved in determining centrosome shape during the syncytial mitoses which lead to the formation of the blastoderm in early Drosophila embryos. PMID- 1612127 TI - Effect of an arginine-specific ADP-ribosyltransferase inhibitor on differentiation of embryonic chick skeletal muscle cells in culture. AB - Primary cultures of embryonic chick skeletal myogenic cells were used as an experimental model to examine the possible role of mono(ADP-ribosyl)ation reactions in myogenic differentiation. Initial studies demonstrated arginine specific mono(ADP-ribosyl)transferase activity in the myogenic cell cultures. We then examined the effect of a novel inhibitor of cellular arginine-specific mono(ADP-ribosyl)transferases, meta-iodobenzylguanidine (MIBG), on differentiation of cultured embryonic chick skeletal myoblasts. MIBG reversibly inhibited both proliferation and differentiation of embryonic chick myoblasts grown in culture. Micromolar (15-60 microM) concentrations of MIBG blocked myoblast fusion, the differentiation-specific increase in creatine phosphokinase activity, and both DNA and protein accumulation in myogenic cell cultures. Meta iodobenzylamine, an analog of MIBG missing the guanidine group, had no effect. Low concentrations of methylglyoxal bis-guanylhydrazone, a substrate for cholera toxin with a higher Km than MIBG, also had no effect, but higher concentrations reversibly inhibited fusion. These findings suggest a possible role for mono(ADP ribosyl)ation reactions in myogenesis. In addition, the total arginine-specific mono(ADP-ribosyl)transferase activity increased with differentiation in the myogenic cell cultures, and this increase was also blocked by MIBG treatment. Because high levels of activity were found in the membrane fraction derived from later, myotube cultures, the membrane fraction from 96-h cultures was incubated with [32P]NAD+ and subjected to electrophoresis and autoradiography. Three proteins, migrating at 21, 20, and 17 kDa, that were ADP-ribosylated in the absence, but not the presence, of MIBG were identified. These proteins may be endogenous substrates for this enzyme. PMID- 1612128 TI - Alpha-smooth muscle actin is expressed in a subpopulation of cultured and cloned fibroblasts and is modulated by gamma-interferon. AB - Clinical and experimental investigations have shown that, during wound healing and fibrocontractive diseases, fibroblasts acquire, more or less permanently according to the situation, morphological and biochemical features of smooth muscle (SM) cells including the expression of alpha-SM actin. Primary and passaged cultures of rat and human fibroblasts contain a subpopulation of cells expressing alpha-SM actin. These cells could derive from SM cells and/or pericytes present in the tissue from which cultures have been produced or represent bona fide fibroblasts. We have investigated the presence of alpha-SM actin in fibroblast cultures, clones, and subclones. In all cases the fibroblastic populations studied showed a proportion of alpha-SM actin expressing cells. Even after cloning, we never obtained populations negative for alpha-SM actin. We conclude that alpha-SM actin expression in fibroblastic cultures is not due to contaminant cells but is a feature of fibroblasts themselves. Our results support the view that fibroblastic cells are a heterogeneous population. It has been previously shown that gamma-interferon (gamma-IFN) decreases alpha-SM actin expression in SM cells. In rat and human fibroblasts, gamma-IFN decreases alpha SM actin protein and mRNA expression as well as proliferation. The properties of this cytokine make it a good candidate for exerting an anti-fibrotic activity in vivo. PMID- 1612129 TI - Interaction between growth factors and retinoic acid in the induction of kidney tubulogenesis in tissue culture. AB - Kidney tubulogenesis is the initial step in renal organogenesis. The precise molecular determinants of this pattern formation are presently unknown, although soluble factors, such as growth factors, and insoluble factors, such as extracellular matrix molecules, most likely play fundamental roles in this process. To define the molecular determinants of renal proximal tubule morphogenesis, primary cultures of rabbit renal proximal tubule cells in hormonally defined, serum-free media were treated with transforming growth factor beta 1 (TGF-beta 1), epidermal growth factor (EGF), and the retinoid, all trans retinoic acid (RA), singly or in combination. Utilizing phase contrast and light and transmission electron microscopy, the simultaneous administration of TGF-beta 1 (10 ng/ml), EGF (1 nM), and RA (0.1 nM) transformed a confluent monolayer of renal proximal tubule cells within 5 to 6 days into three-dimensional cell aggregates containing lumens within the interior of the cell clusters. The lumens were bordered by tubule cells possessing a polarized epithelial cell phenotype with extensive microvilli formation and tight junctional complexes along the luminal border. All three factors were necessary and sufficient to induce this phenotypic transformation. Further studies demonstrated that RA promoted the deposition of the A and B1 chains of laminin, a cell attachment protein of the basement membrane, in a small subset of proximal tubule cells in culture, as deduced by indirect immunofluorescent microscopy. Additional studies demonstrated that soluble purified laminin fully substituted for RA in this system to promote renal tubulogenesis when combined with TGF-beta 1 and EGF. These results demonstrate that the growth factors, TGF-beta 1 and EGF, and the retinoid, RA, promote tubulogenesis in adult renal proximal tubule cells in tissue culture in a manner reminiscent of inductive embryonic kidney morphogenesis. These observations define a coordinated interplay between growth factors and retinoids to induce pattern formation and morphogenesis. Furthermore, the demonstration of RA-induced laminin deposition as a critical event in this morphogenic process identifies laminin as a possible target protein for RA to act as a morphogen. PMID- 1612130 TI - Cell surface beta-1,4-galactosyltransferase is associated with the detergent insoluble cytoskeleton on migrating mesenchymal cells. AB - Cell surface beta-1,4-galactosyltransferase (GalTase) partially mediates a variety of cell interactions with laminin-containing matrices, including mesenchymal cell spreading and migration and neurite initiation, by binding to N linked oligosaccharides within the E8 domain of laminin. Previous studies using indirect immunofluorescence have suggested that some surface GalTase colocalizes with actin-containing microfilaments in migrating cells. In this study, we present more direct biochemical evidence showing that surface GalTase is associated with the detergent-insoluble cytoskeleton and that this association is dependent upon the integrity of the cytoskeleton, valency of the anti-GalTase antibody, and migratory status of the cell. Two-thirds of the surface GalTase was associated with the detergent-insoluble cytoskeleton when assayed either by monovalent anti-GalTase Fab fragments or by extracting any detergent-soluble GalTase prior to labeling with intact anti-GalTase IgG. However, 80-100% of the surface GalTase could be induced to associate with the cytoskeleton when cross linked with anti-GalTase IgG prior to detergent extraction. Destabilizing cytoskeleton-protein interactions with high levels of KCl, elevated pH, or cytochalasin B reduced the amount of surface GalTase retained in the detergent insoluble cytoskeleton fraction. Finally, we have shown previously that laminin induces the expression of GalTase onto lamellipodia of migrating cells, and in this study, we show that the laminin-induced increase in surface GalTase is cytoskeletally associated. Collectively, these data suggest that cell surface GalTase participates in cell spreading and migration on laminin by virtue of its association with the cytoskeleton. PMID- 1612131 TI - Induction of B16 melanoma melanogenesis by a serum-free synthetic medium. AB - Cultured murine B16 melanoma cells normally grow as spindle-shaped cells firmly attached to tissue culture flasks. Pellets obtained from harvested B16 melanoma cells are white to grey in color. When the same cells were grown in synthetic, serum-free AIM V medium, cellular morphology and pigmentation were radically altered. Within 3 days of subculture in AIM V, cells rounded up and grew in clusters in suspension. Melanin content increased to greater than 30 times and tyrosinase activity was found to be 10-50 times higher in cells grown in AIM V medium compared to those cultured in normal medium. A concomitant increase in the level of immunoreactive tyrosinase was also induced. The individual growth factors and hormones present in AIM V medium were examined to determine which component(s) stimulates melanogenesis. Only those cells grown in the presence of 2.5% human albumin were stimulated to synthesize melanin. These findings suggest that albumin, or a component associated with albumin, has a major effect upon the regulation of melanogenesis in these cells. PMID- 1612132 TI - Hormonal regulation of the nuclear localization signals of the human glucocorticosteroid receptor. AB - Nuclear localization of the rat glucocorticosteroid receptor (rGR) transiently expressed in COS-7 cells appears to be mediated by two nuclear localization signals, NL1 and NL2, in a hormone-dependent mechanism. We investigated the intracellular distribution of the human GR (hGR) expressed in COS-7 cells, by a different immunohistochemical technique involving immunostaining of cell pellet sections, thus avoiding the use of cell permeabilizing agents and allowing rigorous comparison between successive experiments. With a large set of hGR mutants, we could define determinants of the hGR nuclear localization and compare them with those previously reported for rGR. Our study demonstrated two hormone dependent nuclear localization signals. NL1 activity, overlapping the DNA-binding domain (DBD)-hinge boundary, was repressed by the unliganded ligand-binding domain (LBD), even if the repressed NL1 retained a residual potency to target hGR in the nucleus. Structure/function analysis suggested a bipartite structure of NL1, analogous to that of other nuclear targeting signals (the carboxy-terminal part of DBD between amino acids 478 and 487 and the beginning of the hinge region which includes a basic amino acid stretch between 491 and 498). Upon hormone binding, NL2, located in the LBD, was activated, but was unable by itself to sustain full nuclear localization, which required the derepressed NL1 activity. Only two sequences in the LBD, localized between amino acids 600 and 626 and from amino acid 696 up to the carboxyl-terminal amino acid 777, respectively, were found to inhibit NL1 activity. As previously reported, efficient nuclear retention, mandatory for gene expression, did not required DNA-binding activity. The controversial intracellular localization of the unliganded form of hGR and the role of hsp90 in cytoplasmic localization are further discussed. PMID- 1612133 TI - Ecological implications of metabolic biochemistry: elephant parts and the third secret of life. PMID- 1612134 TI - The matches, achieved by natural selection, between biological capacities and their natural loads. AB - Natural selection tends to eliminate unutilized capacities because of their costs. Hence we ask how large are the reserve capacities by which biological capacities exceed natural loads, and how closely are related biological capacities matched to each other. Measured capacities (Vmax values) of small intestinal brush-border nutrient transporters are typically around twice their natural loads (dietary intakes of their substrates); the ratio is higher for a transporter of a hyperessential nutrient. Preliminary evidence suggests matching of capacities between different steps in carbohydrate metabolism, and between the intestine, liver, kidneys, and spleen. Symmorphosis - the postulated matching of capacities to each other and to loads - is a testable hypothesis of economic design, useful in detecting and explaining cases of apparently uneconomic design. PMID- 1612135 TI - Pathways for oxidative fuel provision to working muscles: ecological consequences of maximal supply limitations. AB - The study of metabolic fuel provision and its regulation has reached an exciting stage where specific molecular events can be correlated with parameters of the organism's ecology. This paper examines substrate supply pathways from storage sites to locomotory muscle mitochondria and discusses ecological implications of the limits for maximal flux through these pathways. The relative importance of the different oxidative fuels is shown to depend on aerobic capacity. Very aerobic, endurance-adapted animals such as long distance migrants favor the use of lipids and intramuscular fuels over carbohydrates and circulatory fuels. The hypothesis of functional co-adaptation between oxygen and metabolic fuel supply systems allows us to predict that the capacity of several biochemical processes should be scaled with maximal oxygen consumption. Key enzymes, transmembrane transporter proteins, glucose precursor supply and soluble fatty acid transport proteins must all be geared to support higher maximal glucose and fatty acid fluxes in aerobic than in sedentary species. PMID- 1612136 TI - Hummingbird flight: sustaining the highest mass-specific metabolic rates among vertebrates. AB - Resting and maximal mass-specific metabolic rates scale inversely with body mass. Small hummingbirds achieve the highest known mass-specific metabolic rates among vertebrate homeotherms. Maximal capacities for O2 and substrate delivery to muscle mitochondria, as well as mitochondrial oxidative capacities in these animals may be at the upper limits of what are structurally and functionally possible given the constraints inherent in vertebrate design. Such constraints on the evolutionary design of functional capacities may play an important role in determining the lower limits to vertebrate homeotherm size and the upper limits to mass-specific metabolic rate. PMID- 1612137 TI - Metabolic biochemistry and the making of a mesopelagic mammal. AB - Large seals such as northern and southern elephant seals and Weddell seals are able to dive for startling duration and enormous depth. The current dive duration record is 120 minutes (recorded for the southern elephant seal); the current depth record is 1.5 km (recorded for the northern elephant seal). Equally striking is the widespread observation that these seals when at sea spend close to 90% of the time submerged and often at great depth. For practical purposes, these species can be viewed as true mesopelagic animals when they are at sea. A review of current knowledge indicates that low power output but high efficiency metabolic functions of skeletal muscles coupled with inherently low (and potentially further suppressible) metabolic rates constitute strategic biochemical components in the 'making' of a mesopelagic mammal. PMID- 1612139 TI - Structural characteristics and distribution of satellite cells along crayfish muscle fibers. AB - The distribution of satellite cells (sc) in long-sarcomere muscle fibers from the carpopod extensor muscle of the crayfish (Astacus fluviatilis) has been studied electron-microscopically. The sc are spindle-shaped and are oriented parallel to the long axis of a fiber. The mean lengths of sc nuclei (17.00 microns) and that of myonuclei (18.35 microns) differ non-significantly. In older animals, the mean ratio of the number of sc nuclei to the total number of nuclei (sc nuclei + myonuclei) is 0.0716, 0.0848, and 0.034 for the tendon, central and shell segments, respectively. The corresponding values for younger animals are 0.158, 0.166, and 0.081. The mean numbers of sc nuclei per mm of a fiber are 94, 117, and 47 (older animals), and 164, 117, and 94 (younger animals) for the tendon, central and shell segments, respectively. The high incidence of sc per unit fiber length in crayfish may be related to the fact that crayfish muscle fibers have a much larger diameter than vertebrate muscle cells. PMID- 1612138 TI - The biochemistry of natural fasting at its limits. AB - There are several groups of animals that are adapted for extremely long duration fasting as part of their reproductive cycle. Penguins, bears and seals routinely fast without food or water for months at time. However, they do not 'starve', as the biochemical implications of starving are very different from those of successful fasting. There are distinct biochemical adaptations in lipid, carbohydrate and especially protein metabolism that allow these animals to survive. It appears, at least for penguins and seals, that the duration of the fast may be limited by changes that occur in biochemical regulation near the ned of the fast. In all of these species, the biochemistry of fasting and the ecological and behavioral demands of their breeding cycles are closely interrelated. PMID- 1612140 TI - Myocardial dystrophin immunolocalization at sarcolemma and transverse tubules. AB - Using monoclonal antibodies against two different regions of the helical rod part of dystrophin, we have localized dystrophin on both plasma membrane and transverse tubules in cardiac muscle of man and several animal species. The staining persisted after experimental ischaemia, and was observed in long standing heart disease. No immunostaining was seen at the intercalated discs. In skeletal muscle the same two antibodies stained only the plasma membrane. PMID- 1612142 TI - The second 100,000. PMID- 1612141 TI - Insecticidal effects of essential oils. A study of the effects of essential oils extracted from eleven Greek aromatic plants on Drosophila auraria. AB - Effects of the essential oils (EOs) extracted from eleven aromatic plants belonging to the Lamiaceae family (common in the Greek flora) were examined upon three different developmental stages of Drosophila auraria. All of the EOs examined exhibited insecticidal effects, either by preventing egg hatching, or by causing the death of larvae and adult flies. In several cases, malformation and/or prohibition of puparium formation was also observed. PMID- 1612143 TI - Adolescent knowledge and attitudes about abortion. AB - A focus-group study of adolescents from cities across the United States revealed that they lacked accurate knowledge about abortion and the laws governing it. Most expressed erroneous beliefs about abortion, describing it as medically dangerous, emotionally damaging and widely illegal. The study also revealed that antiabortion views, conservative morality and religious beliefs were the primary sources of these adolescents' attitudes toward abortion. In general, the participants in the study said they were personally opposed to abortion, but supported its continued legality as a woman's choice. Although most of the teenagers expressed positive feelings toward parents, they did not feel that mandatory parental involvement would be helpful, and in some cases could cause harm. PMID- 1612144 TI - Premature discontinuation of contraception in Australia. AB - Life-history data from a nationally representative survey of Australian women were used to examine discontinuation of contraceptive methods because of accidental pregnancy, side effects or dissatisfaction. The pill was the most successfully used method, with a first-year discontinuation rate of 10% for all three reasons. Side effects dominated the reasons for the premature discontinuation of both the pill and the IUD, while the reasons for discontinuing the condom stemmed equally from pregnancy and dissatisfaction with the method. Discontinuation of the diaphragm resulted largely from accidental pregnancy. Hazards models were used to identify the correlates of discontinuation of each method. Predictors of premature discontinuation reflect the availability of methods, physiological reactions to them and the social characteristics of their users. Discontinuation of the pill because of side effects or dissatisfaction was more likely among poorly educated women, non-Protestants and recent users, and less likely among teenagers. Discontinuation of the IUD was related entirely to physiological factors: Nulliparous women and users of unmedicated devices were at a greater risk than other women of accidental pregnancy, and nulliparous women were at greater risk of discontinuation associated with side effects. Nulliparous women were also more likely to discontinue the condom because of pregnancy, as were non-Protestants and the Australian-born. PMID- 1612145 TI - Comparing outcomes in a statewide program for adolescent mothers with outcomes in a national sample. AB - One-year outcomes for 1,004 participants in a statewide program for pregnant and parenting teenagers were compared with outcomes for 790 adolescent mothers included in the National Longitudinal Survey of Youth. The program group was substantially younger and included more black women and fewer married teenagers than the national sample. Controlling for these and other baseline differences revealed that program participants were significantly more likely than the national sample to be enrolled in school, to be employed and to have avoided a subsequent pregnancy 12 months later. Several baseline variables, including age at first birth, ethnicity, education and living arrangements, were also predictive of one-year outcomes. PMID- 1612146 TI - Family planning, sexually transmitted diseases and contraceptive choice: a literature update--Part I. AB - Couples who use contraceptives not only protect themselves against unwanted pregnancies, but also may reduce their risk of becoming infected with a sexually transmitted disease (STD). No currently available method, however, is highly effective in protecting simultaneously against pregnancy and infection. Thus, couples who place high priority on minimizing both risks may have to use two methods. The need for contraceptive methods that provide effective protection against both pregnancy and STDs has been intensified by the HIV epidemic, but progress has been slowed by the lack of integration between the STD and family planning fields. The first part of this two-part article discusses the similarities and differences between the two fields, examines the impact of STDs on contraceptive use and services, and reviews the scientific literature dealing with the effects of condoms, spermicides and barrier-and-spermicide methods on the risk of STD transmission. Part II (which will appear in the next issue) examines what is known about the effects of oral contraceptives, the IUD, tubal sterilization and abortion on reproductive tract infections. The second part also includes a discussion of the trade-offs involved in choosing a contraceptive and presents estimates of the first-year rates of unplanned pregnancy and gonorrhea infection (given an infected partner) that would occur among women using various contraceptive methods. PMID- 1612147 TI - Abortion trends in 1987 and 1988: age and race. PMID- 1612148 TI - In defense of a call to action. PMID- 1612149 TI - Adolescents at risk. PMID- 1612150 TI - Clinical significance of studying resting CO2 drive after CO2 unloading. PMID- 1612151 TI - Growing consensus in asthma? PMID- 1612152 TI - Ventilatory responsiveness to carbon dioxide below the normal control point in conscious normoxic humans. AB - A recently developed CO2 pulse technique was used to test for ventilatory sensitivity to CO2 in four normal men following 2 min voluntary hyperventilation down to an end-tidal CO2 tension (PETCO2) of 20 mmHg (2.7 kPa). Pure CO2 was injected into the inspiratory limb of a breathing circuit at 0.4 l.min-1 for 30 s and any small ventilatory response was detected against background noise by ensemble-averaging of multiple runs. Following hyperventilation, ventilation was initially often above control and apnoea was not seen. In one subject, the ventilatory response to the CO2 pulse was barely detectable either before or after hyperventilation. In another subject, there was a response to pulses given before hyperventilation and 3 and 5.5 min after hyperventilation but not 30 s after hyperventilation when PETCO2 was about 25 mmHg (3.3 kPa) and rising. In the two remaining subjects ventilatory responses were seen to CO2 pulses started 30 s after hyperventilation, although PETCO2 following the pulse remained some 5 mmHg (0.7 kPa) below baseline. We conclude that in some subjects the PETCO2 threshold lies well below the normal PETCO2. The technique is tedious for the experimental subject because of the large number of repetitions required and, therefore, unsuitable for a study on a large number of subjects. PMID- 1612153 TI - Vascular and cardiac reactivity in pulmonary hypertension due to chronic obstructive lung disease: assessment with various oxygen concentrations. AB - The aim of the present work was to evaluate vasoreactivity in patients with pulmonary hypertension related to chronic obstructive lung disease. This was done by comparing haemodynamic data recorded while patients were breathing room air, and hypoxic and hyperoxic mixtures. We estimated the role of vasoconstriction in determining the level of pulmonary hypertension. This study included 26 patients with moderate pulmonary hypertension mean pulmonary arterial pressure (MPAP) = 27.3 +/- 1.2 mmHg) secondary to chronic obstructive lung disease (COLD), forced expiratory volume in one second (FEV1) = 0.95 +/- 0.13 l; arterial oxygen tension (PaO2) = 8.7 +/- 0.25 kPa). After insertion of a thermodilution catheter in the pulmonary artery and a cannula in the femoral artery, mixtures containing 15, 21, 30 and 100% oxygen were randomly administered for 20 min each. As fractional inspiratory oxygen (FIO2) increased, MPAP decreased relatively less than cardiac index. Cardiac output was at its highest during room air breathing and the hypoxic mixture did not lead to a further increase. Unlike normal subjects, in whom adjustment of cardiac output is achieved by heart rate alone, haemodynamic regulation in these patients also involved stroke volume. Variations in MPAP and cardiac index were strongly correlated with arterial oxygen saturation (SaO2). The greatest variations were noted in the patients with the highest pulmonary hypertension. Under normoxic and hyperoxic condition the relationship between pulmonary artery driving pressure and cardiac index was linear and its slope steeper in patients having the highest pulmonary hypertension at steady state.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612154 TI - Alpha 1-antitrypsin alleles in patients with pulmonary emphysema, detected by DNA amplification (PCR) and oligonucleotide probes. AB - Alpha 1-antitrypsin (AAT) deficiency is a serious predisposing factor for the development of pulmonary emphysema. Twelve representative Danish families were studied. AAT typing was performed as a comparative study between the traditional protein typing by isoelectrical focusing and the deoxyribonucleic acid (DNA) technique of enzymatic amplification and subsequent typing with radioactively labelled oligonucleotide probes. On the basis of clinical and radiological signs of pulmonary emphysema, 25 patients were selected. AAT typing was performed by use of the two techniques in combination, in search for new point-mutations among the patients. Results obtained with the two techniques were discordant in one patient, suggesting an unknown variant. The unexpectedly high PiZ frequency of 0.22 found in the study group is discussed. PMID- 1612155 TI - Bronchial mucosal manifestations of atopy: a comparison of markers of inflammation between atopic asthmatics, atopic nonasthmatics and healthy controls. AB - We studied the role of atopy, as defined by positive skin tests to common inhalant allergens, in allergic bronchial inflammation. Endobronchial biopsies were taken via the fibreoptic bronchoscope in 13 symptomatic atopic asthmatics, 10 atopic nonasthmatics, and 7 normals. The numbers of mast cells, identified in the submucosa by immunohistochemistry using the AA1 monoclonal antibody against tryptase, were no different between the three groups, but electron microscopy showed that mast cell degranulation, although less marked in atopic nonasthmatics, was a feature of atopy in general. The numbers of eosinophils, identified by immunohistochemical staining using the monoclonal anti-eosinophil cationic protein antibody, EG2, were greatest in the asthmatics, low or absent in the normals and intermediate in the atopic nonasthmatics. In both atopic groups eosinophils showed ultrastructural features of degranulation. Measurements of subepithelial basement membrane thickness on electron micrographs showed that the collagen layer was thickest in the asthmatics, intermediate in the atopic nonasthmatics and thinnest in the normals. The results suggest that airways eosinophilia and degranulation of eosinophils and mast cells, as well as increased subepithelial collagen deposition, are a feature of atopy in general and suggest that the degree of change may determine the clinical expression of this immune disorder. PMID- 1612156 TI - Time trends in repeated spirometry in children. AB - In a study on acute health effects of air pollution in the Netherlands, pulmonary function has been measured repeatedly in children aged 7-11 yrs. In study periods of approximately 3 months, 6-10 tests have been made in a group of 1,621 children. The spirometric data have been examined for the presence of trends of pulmonary function with day of study, independent of air pollution. Peak expiratory flow (PEF) increased more than expected from normal lung growth, whereas for maximal mid-expiratory flow (MMEF) a decrease with time was observed. For forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) a smaller than expected increase with time was observed. The observed deviation from the expected pattern was larger for the children with a one week interval between successive tests than for the children with a three week interval. For FVC and FEV1 a non-linear relationship with time was observed, for PEF and MMEF this relationship was approximately linear. The particular changes of spirometric variables with time need to be taken into account when repeated lung function tests are performed to investigate acute effects of air pollution exposure. PMID- 1612157 TI - The interaction of Streptococcus pneumoniae with intact human respiratory mucosa in vitro. AB - The interaction of Streptococcus pneumoniae with human ciliated upper respiratory mucosa was studied in an agar-embedded organ culture of nasal turbinate tissue, which only exposed the intact epithelial surface and its secretion. The ciliary beat frequency, measured along the edge of the organ culture, was slowed by 13% in the presence of S. pneumoniae after 16 h (p less than 0.05) compared with the control, and by 24% after 24 h (p less than 0.01). Light microscopy showed bacteria in a thickened gelatinous layer, which obscured the surface of the organ culture. Transmission and scanning electron microscopy confirmed the association of bacteria with the gelatinous layer above an epithelial surface which showed only minor changes compared to uninfected control organ cultures. Contact between bacteria and normal or damaged epithelial cells was not seen. S. pneumoniae in organ culture developed projections from their surface, which were not present after broth culture. S. pneumoniae interactions with epithelial-derived secretions, the formation of a thickened gelatinous layer, and the effects of bacterial toxins on ciliary motility, may be important during colonization of the respiratory tract. PMID- 1612158 TI - Sensitivity to sensitins and tuberculin in Swedish children. IV. The influence of BCG-vaccination. AB - BCG-vaccinated schoolchildren, 8-9 yrs of age, were simultaneously tested on separate arms with tuberculin and a sensitin. Using the 6 mm cut-off they reacted in 49% to two tuberculin units purified protein derivative (PPD RT23), in 67% to 0.1 micrograms Mycobacterium avium sensitin RS10, and in 58% to 0.1 micrograms M. scrofulaceum sensitin RS95. The corresponding figures for non-BCG-vaccinated schoolchildren of the same age tested at the same time were 3, 25 and 32%, respectively. The results indicate a stimulating influence of BCG-vaccination on tuberculin and sensitin reactivity. Since the sensitin reactions were the larger ones, these reactions were not only due to the vaccination. The BCG-vaccinated schoolchildren seem to have acquired infections by atypical mycobacteria despite vaccination. PMID- 1612159 TI - Inter-machine variability in the stability of continuous positive airway pressure. AB - Two studies were performed to investigate the differences in pressure stability performance of the continuous positive airway pressure (CPAP) machines used by our patients. The variations of mask pressures during each respiratory cycle were measured during overnight studies of two groups of patients with obstructive sleep apnoea, who were using either a Sleep-Easy III CPAP machine or a Si-Plan CPAP unit. The patients were well-matched for age, weight and neck circumference. The group using the Si-Plan unit had more constant mask pressures and were using lower CPAP pressures (mean 10.6 cmH2O) than those using the Sleep-Easy III machine (mean 13.8 cmH2O) (p less than 0.02). The pressure stability performance of five CPAP machines used by our patients was also compared using standardized simulated patient breaths produced by a negative pressure cuirass pump. There were large differences between the machines in ability to maintain a constant pressure. Using a tidal volume of 0.5 l and peak flow rates of between 20-40 l.min-1 the pressure variation ranged from 0-67% of the minimum inspiratory pressure. The maintenance of a constant pressure during inspiration and expiration lowers the mean pressure required to eliminate obstructive sleep apnoeas and reduces the likelihood of pressure related side-effects. PMID- 1612160 TI - Alveolar haemorrhage with pleural effusion as a manifestation of epithelioid haemangioendothelioma. AB - A 22 year old male was admitted with haemoptysis. A chest X-ray showed bilateral confluent alveolar infiltrates. Bronchoscopy revealed blood oozing from all bronchopulmonary segments. Open lung biopsy disclosed bilateral effusions and large necrotizing nodules with pleural adhesions. Histological examination showed tumour cells, which were negative to epithelial and embryogenic markers but positive to factor VIII. This confirmed the diagnosis of an epithelioid haemangioendothelioma. This rare tumour, usually has an indolent course, whereas in our case it was complicated by alveolar and intrapleural bleeding. PMID- 1612161 TI - Trichosporon beigelii pneumonitis following busulphan-induced leucopenia. AB - We present a 41 yr old male, who died of respiratory failure due to infiltration of Trichosporon beigelii (cutaneum) into the pulmonary interstitial spaces with systemic dissemination. Busulphan-induced leucopenia in the chronic phase of chronic myelogenous leukaemia had progressed before this infection developed. In leukaemic patients with profound leucopenia, interstitial pneumonitis due to T. beigelii should be considered as a possible cause of otherwise unexplained hypoxaemia. PMID- 1612162 TI - Tumour in a 14 year old girl. PMID- 1612163 TI - International consensus report on diagnosis and treatment of asthma. National Heart, Lung, and Blood Institute, National Institutes of Health. Bethesda, Maryland 20892. Publication no. 92-3091, March 1992. PMID- 1612164 TI - HIV infection among tuberculous patients in Morocco. PMID- 1612165 TI - Erythromycin inhibits Cl secretion. PMID- 1612166 TI - Nonspecific challenge test for the diagnosis of asthma in a general population sample. PMID- 1612167 TI - Anthrax in Delaware county: a historical perspective. PMID- 1612168 TI - Physician covenants not to compete under Delaware law. PMID- 1612169 TI - Physicians' health. PMID- 1612170 TI - Old Joe and Dr. Todd's fuzzy ethics. PMID- 1612171 TI - University of Delaware Medical Technology Program to continue. PMID- 1612172 TI - [Internal live strain. Color technique for deep staining]. PMID- 1612173 TI - [Experiences with Empress ceramic. Preparation of inlays and onlays]. PMID- 1612174 TI - [Complete dentures and fixed partials. Provocation for every ceramic worker]. PMID- 1612175 TI - Mucin complexes: characterization of the "link" component of submandibular mucus glycoprotein. AB - 1. Analysis of the submandibular saliva revealed that the secretion consists of mucin complexed with 150 kDa fibronectin fragment and DNA. 2. The kallikreins, secreted by the submandibular gland, appear to be responsible for the fibronectin fragmentation, since an identical peptide was also generated when fibronectin was subjected to incubation with the submandibular saliva or the purified enzyme. 3. The results provide evidence that the 150 kDa glycopeptide so-called salivary mucin "link" component is neither an integral part of the mucin molecule, nor linked to mucin subunits by disulfide bonds, but is a fibronectin fragment which associates with mucin. 4. Using mucin monoclonal antibody (3G12), it was revealed that the nonglycosylated (naked) 8-12 kDa fragment of the mucin molecule is responsible for the interaction of mucin with other components of saliva. 5. Under physiological conditions, the interaction of mucin with fibronectin on the luminal surfaces may be relevant in building mucous barrier and protection of the delicate oral epithelium from damage. PMID- 1612176 TI - Antibodies to neuropeptide precursors expressed as fusion proteins in E. coli. Their use to examine neuropeptide biosynthetic pathways, intracellular trafficking and physiological activities. PMID- 1612177 TI - Immunohistochemical localization of phospholipase A2 in the bovine seminal vesicle and on the surface of the ejaculated spermatozoa. AB - 1. Approximately 150-fold purified phospholipase A2 (PLA2) from bovine seminal vesicle fluid was injected into rabbit to prepare antibodies. 2. Produced antisera blocked PLA2 activity in bovine seminal plasma, seminal vesicles and its fluid and it gave single precipitation lines with the same samples. No cross reactivity was detected with other reproductive tissues of bull as well as human seminal plasma. 3. Using indirect peroxidase technique PLA2 was localized in the apical part of epithelia cells of the bull seminal vesicle and also some minor immunohistochemical reactions were observed in the tubular lumen. Indirect peroxidase staining gave weak or no reaction at all to seminal vesicles of immature bulls. This suggests that the enzyme may be under hormonal control. 4. By indirect immunofluorescence method ejaculated spermatozoa of bull revealed immunoreaction which was not uniform and it was restricted to the middle piece, acrosome as well as postacrosomal region, but no specific immunostaining could be found on the surface of the epididymal spermatozoa. 5. Enzyme visualization by immunoelectron microscopic labelling showed a predominant localization in membrane particles inside the lumen of bovine seminal vesicle but some gold particles were also seen in granules, larger vacuoles and in cytoplasm of epithelia cells. PMID- 1612178 TI - The isolation and partial characterization of trypsinogen, pancreatic secretory trypsin inhibitor and multiple forms of chymotrypsinogen and trypsin from the pancreas of the ostrich (Struthio camelus). AB - 1. PSTI, two chymotrypsinogens and two trypsins were purified to homogeneity by acid extraction, salt fractionation, SP-Sephadex C-50 chromatography and RP-HPLC. 2. A third chymotrypsinogen, a trypsinogen and another trypsin were purified using an alkaline extraction procedure, followed by Trasylol- and Benzamidine Sepharose affinity chromatography and hydroxylapatite chromatography. 3. The enzymes differed in amino acid composition as well as in specific activities towards synthetic amidase and esterase substrates. 4. N-terminal amino acid sequences were determined for one chymotrypsinogen and one trypsin. PMID- 1612180 TI - Alterations in the level of insulin receptor and GLUT-4 mRNA in skeletal muscle from rats fed a kidney bean (Phaseolus vulgaris) diet. AB - 1. A decline in the level of circulating insulin was observed in rats fed a diet containing kidney bean. 2. Consumption of a diet containing kidney bean caused an increase in the level of mRNAs for the insulin receptor (327%) and GLUT-4 (185%) in the gastrocnemius muscle. In contrast there was only a small increase in the amount of actin mRNA (125%). Since the kidney bean-fed rats are euglycaemic the results suggest that insulin receptor and GLUT-4 mRNA levels are regulated in response to circulating insulin concentrations rather than glucose. 3. No increases in the level of insulin receptor and actin mRNA were evident in the soleus muscle of rats fed the diet containing kidney bean; however a decline was observed in the level of GLUT-4 mRNA. 4. It is proposed that a component of kidney beans, most likely the lectin phytohaemagglutinin, has systemic effects which lead to changes in expression of the insulin receptor and GLUT-4 genes and to the sensitivity of muscle to insulin. PMID- 1612179 TI - Comparison of the multicatalytic proteinases isolated from the nucleus and cytoplasm of chicken red blood cells. AB - 1. Two chromatographically distinct multicatalytic proteinases (MCP's) were isolated from the cytoplasm of chicken red blood cells and one MCP was purified from the nuclei. 2. The nuclear and the majority (97-99%) of the cytoplasmic multicatalytic proteolytic activity were chromatographically similar and differed from the minor cytoplasmic activity in their elution from hydroxylapatite, number of subunits on 2D-SDS-PAGE, and in their sensitivity to proteinase inhibitors. 3. Dichloroisocoumarin, a serine proteinase inhibitor, inhibited the hydrolysis of fluorogenic peptides but stimulated the degradation of casein by the multicatalytic proteinases suggesting that this enzyme has distinct active sites for protein and peptide hydrolysis. PMID- 1612181 TI - Inhibition of HIV-1 proteinase by metal ions. AB - 1. Certain metal ions have been identified as inhibitors (IC50 1-20 microM) of the aspartic proteinase of Human Immunodeficiency Virus Type 1 (HIV-PR). 2. By contrast most simple metal ions do not inhibit this enzyme. 3. Those that did inhibit have in common a high charge/size ratio or "hard" acidic nature, preferring to combine covalently with oxygen donor ligands. 4. Some evidence from independent X-ray crystal structure determinations suggests that the metalloinhibitors identified here may bind in the active site of the enzyme via coordination to the carboxylate side chains of the essential active site residues Asp 25 and 125. 5. Although the measured inhibition is only microM, very few enzyme-inhibitor interactions can be taking place and so more complex metalloinhibitors with ligands that can also bind to peptide side chains of the enzyme might be significantly more potent inhibitors of HIV-PR and of viral replication. PMID- 1612182 TI - Effect of pH on the modulation of rat osseous plate alkaline phosphatase by metal ions. AB - 1. Metal ions other than zinc and magnesium were effective in modulating the activity of rat osseous plate alkaline phosphatase. 2. Increasing pH had remarkable effects on the modulation of rat osseous plate alkaline phosphatase. 3. The modulation of enzyme activity by zinc, manganese and cobalt ions was slightly affected by pH variations. 4. Zinc ions were stimulatory for the enzyme at very low concentrations (50 nM). Above 50 nM zinc ions inhibited the enzyme by displacing magnesium ions. 5. Calcium ions were inhibitors of alkaline phosphatase (Kd = 10 microM) whereas manganese (Kd = 1.3 microM) and cobalt (Kd = 0.2 microM) ions were stimulatory in the pH range 8.0-10.0. PMID- 1612183 TI - Possible involvement of manganese in the catalytic mechanism of bovine liver arginase. AB - 1. Bovine liver arginase followed Michaelis-Menten kinetics in the pH range of 4.5-9.0. The variation of vi with pH implied that a basic group (pKa 8.7) functions at the catalytic site. 2. Treatment of the enzyme with N-ethylmaleimide showed that there are no critical sulfhydryl groups on the enzyme. 3. The less selective reagent, 3-bromopyruvate, caused biphasic inactivation which was unaffected by the presence of ornithine. 4. The data pointed against critical involvement of active site amino acid side chains in the catalytic sequence in arginase. 5. The observed pH-rate profile may reflect ionization of metal-bound water. PMID- 1612184 TI - The development of resistance to the lipogenic effects of insulin in brown and white adipose tissue of spontaneously type II diabetic male CBA/Ca mice. AB - 1. Lipogenesis in brown adipose tissue and white adipose tissue (WAT) was measured in vivo in spontaneously type II diabetic male CBA/Ca mice. 2. Lipogenic rates rose sharply in brown adipose tissue between the third and fourth month of life, concomitant with the onset of hyperinsulinaemia. However, lipogenic rates fell between the fourth and fifth month of age, and remained low, despite increasing circulating insulin concentrations. 3. Lipogenesis in white adipose tissue showed a modest response to hyperinsulinaemia followed by increasing resistance to elevated insulin concentrations after 5 months of age. 4. Studies involving either the injection of insulin or the intubation of glucose provided further evidence for the development of insulin resistance in both brown and white adipose tissue. PMID- 1612185 TI - Intralobular localization of different cytochrome P-450 form dependent monooxygenase activities in the liver of normal and inducer-treated rats. AB - 1. Isolated periportal (PP) and perivenous (PV) hepatocytes from normal and inducer-treated rat livers were used to examine the following: intralobular localization of cytochrome P-450IA, P-450IIB, P-450IIE and P-450IIIA dependent monooxygenase activities and effects of phenobarbital (PB), beta-naphthoflavone (BNF) and pregnenolone-16 alpha-carbonitrile (PCN) on the zonal induction of these monooxygenases. 2. 7-Ethoxyresorufin O-deethylase (7EROD), 7 pentoxyresorufin O-dealkylase (7PROD) and N-nitrosodimethylamine N-demethylase (NAND) activities of PP hepatocytes were not significantly different from those of PV hepatocytes. 3. Ethylmorphine N-demethylase (EMND) activity was significantly higher in PV hepatocytes than in PP hepatocytes of normal rats. 4. EMND activity was induced by PCN and PB treatments. The response of EMND activity to PCN treatment was higher in PP hepatocytes than that in PV hepatocytes, and as a result the PV dominance disappeared following PCN treatment. 5. Extents of the response of this activity to PB treatment were similar in PP and PV hepatocytes, and PV dominance remained unchanged even after induction. PMID- 1612186 TI - Purification and properties of the L-amino acid oxidase from monocellate cobra (Naja naja kaouthia) venom. AB - 1. The L-amino acid oxidase of the monocellate cobra (Naja naja kaouthia) venom was purified to electrophoretic homogeneity. The molecular weight of the enzyme was 112,200 as determined by Sephadex G-200 gel filtration chromatography, and 57,400 as determined by SDS-polyacrylamide gel electrophoresis. 2. The enzyme had an isoelectric point of 8.12 and a pH optimum of 8.5. It showed remarkable thermal stability, and, unlike many venom L-amino acid oxidase, was also stable in alkaline medium. The enzyme was partially inactivated by freezing. 3. The enzyme was very active against L-phenylalanine and L-tyrosine, moderately active against L-tryptophan, L-methionine, L-leucine, L-norleucine, L-arginine and L norvaline. Other L-amino acids were oxidized slowly or not oxidized. 4. Kinetic studies suggest the presence of a side-chain binding site in the enzyme, and that the binding site comprises of at least four hydrophobic subsites. PMID- 1612187 TI - Amino acid composition and immunochemical properties of AcPase III and AcPase IV representing glycoforms of the lower molecular weight, tartrate-resistant acid phosphatase of the frog liver. AB - 1. Amino acid composition and immunological properties of the frog liver LMW AcPase forms: AcPase III and IV were examined. 2. AcPase III and IV show nearly identical amino acid composition and close immunological similarity. 3. These results indicate protein identity of both the enzyme forms and together with our previous data [Kubicz A., Szalewicz A. and Chrambach A., Int. J. Biochem. 23, 413 419 (1991)] demonstrate that generation of AcPase III and IV is a modification of the same enzyme protein by glycosylation processes. 4. Differences in immunoreactivity between AcPase III and IV were observed and discussed to be due to their altered conformations. PMID- 1612188 TI - Studies on phospholipase A2 in human seminal plasma. AB - 1. Human seminal plasma and posterior lobe of prostate was found to have phospholipase A2 (PLA2) activity hydrolysing phosphatidylethanolamine with 14C labelled linoleic and arachidonic acid. 2. A negative relationship was between sperm count and PLA2 activity in human seminal plasma. 3. The purified PLA2 from human seminal plasma showed high affinity to heparin, sensitivity toward p bromophenacyl bromide, Pb2+, dithioerythritol and EDTA and it was activated by Ca2+ and Mn2+. 4. The purified PLA2 had alkaline pH optimum (7.5-10.0) and pI value of 5.3. In SDS-PAGE enzyme preparation resulted in two bands with mol. wt of 14,000 and 16,000. PMID- 1612189 TI - Rapid preparation of native alpha and beta chains of human hemoglobin. AB - 1. Current procedures for the isolation of native chains of hemoglobin employ two ion exchange columns for each chain and result in readily autoxidizable chains with measurable contamination by Hb and Hg. 2. In the new procedure, altered buffer conditions on the first column reduce Hb contamination from 2 to 5% to less than 1%, the limit of detectability. 3. The second column and lengthy washes with beta mercaptoethanol are replaced by incubation with DTT for 1 min for alpha chains and, for beta chains, three incubations with DTT and separations by gel filtration. The residual Hg is less than 0.1%. 4. Oxidations in the previous procedure resulted in low yields and unreliable spectroscopic assessments of bound Hg. The new procedure resulted in a simple UV assay for Hg-free chains. 5. Hemoglobin reconstituted from these oxy-chains was identical to native Hb in oxygen binding equilibria and in the kinetics of CO binding following laser photolysis. PMID- 1612190 TI - Inhibition of gluconeogenesis, ureogenesis and drug oxidation by redox cycler quinone in isolated mouse hepatocytes. AB - 1. The effect of a redox cycler and arylator (menadione) and a pure arylator quinone (benzoquinone) was studied on different NADPH generating and consuming processes in isolated mouse hepatocytes. 2. Menadione inhibited gluconeogenesis from alanine but not from fructose or glycerol. 3. Drug oxidation measured as aniline hydroxylation and aminopyrine N-demethylation could be inhibited by menadione in microsomal membrane and in isolated hepatocytes both from fed or fasted animals. 4. Ureogenesis in isolated hepatocytes from fed mice could not be inhibited even by high concentration of menadione, while in cells from fasted animals menadione was inhibitory at high concentration in the presence of gluconeogenic precursor and at lower concentration in the absence of it. 5. Benzoquinone did not inhibit the above mentioned processes. PMID- 1612191 TI - Heterogeneity in pancreatic beta-cell population. AB - All pancreatic beta-cells are identified by specific morphological characteristics. Similarity in microscopic features is not necessarily associated with identity in functional properties. In vitro studies on isolated rat beta cells have indicated intercellular differences in the threshold for glucose induced shifts in metabolic redox state. The cellular heterogeneity in glucose sensitivity results in a dose-dependent recruitment of glucose-exposed beta-cells into biosynthetic and secretory activities. The molecular basis of this diversity is not known. Indirect evidence supports the concept that the in situ pancreatic beta-cell population is also composed of functionally diverse subpopulations. The heterogeneity in glucose responsiveness is expected to create subpopulations of beta-cells with either constant, fluctuating, or occasional glucose-dependent functions; whether any subpopulation is preferentially responsive to other regulatory factors and/or committed to other activities is unknown. Morphological markers may help identify beta-cell subpopulations in situ and quantify their size in conditions known to affect total beta-cell mass or function. The concept of a functionally heterogeneous beta-cell population influences views on the role of pancreatic beta-cells in health and disease. PMID- 1612192 TI - Antibodies to GAD and tryptic fragments of islet 64K antigen as distinct markers for development of IDDM. Studies with identical twins. AB - Insulin-dependent diabetes mellitus (IDDM) is associated with antibodies to a 64,000-M(r) islet cell protein, at least part of which is identified as glutamic acid decarboxylase (GAD). These antibodies are detected as two distinct antibody specificities to 50,000-M(r) and 37,000/40,000-M(r) tryptic fragments of the autoantigen (50K and 37K antibodies, respectively). We determined the frequencies of antibodies to intact GAD, tryptic fragments of islet 64,000-M(r) antigen, islet cell antibodies (ICAs), and insulin autoantibodies (IAAs) in sera from 58 nondiabetic identical twins of patients with IDDM, of whom 12 subsequently developed diabetes. ICA, antibodies to intact GAD, and those to tryptic fragments were detected at similar frequencies in prediabetic twins (67-75%), but only 25% had IAA. Of 46 twins who remain nondiabetic, GAD antibodies, 50K antibodies, and ICA were detected in 6 (13%), 7 (15%), and 5 (11%), respectively, whereas only 1 (2%) possessed 37K antibodies and 2 (4%) had IAA. Eight of 9 twins with 37K antibodies and all 6 twins with ICA greater than 20 Juvenile Diabetes Foundation U have developed diabetes. Antibodies to GAD are sensitive markers for diabetes development but may also be present in genetically susceptible individuals who are unlikely to develop disease. Antibodies to 37,000/40,000-M(r) fragments of the 64,000-M(r) antigen or high-titer ICA were the best markers for diabetes development in these twins. PMID- 1612193 TI - Concordant glucose induction of glucokinase, glucose usage, and glucose stimulated insulin release in pancreatic islets maintained in organ culture. AB - Using cultured islets as the experimental system, this study established dosage response and time-dependency curves of the inductive glucose effect on glucose stimulated insulin release, glucose usage, and glucokinase activity. Glucose stimulated insulin release in islets cultured for 1, 2, or 7 days was increased as a function of glucose concentration in the culture medium and as a function of time. Glucose usage in the cultured islets showed a close relationship with glucose concentration in the culture medium at both 2 and 7 days of culture. Glucokinase activity increased in islets cultured for 1, 2, or 7 days as a function of increasing glucose concentrations in the culture medium and as a function of time. The V(max) of glucokinase in islets cultured for 7 days in medium containing 30 mM glucose was twice the value of freshly isolated islets and was almost fivefold higher than that in islets cultured for 7 days in 3 mM glucose. The glucose induction of glucose-stimulated insulin release, of glucose usage, and of glucokinase activity were tightly correlated. The biochemical mechanisms of glucose induction of islet glucokinase were further studied. Immunoblotting with an antibody against C-terminal peptide of glucokinase showed that densities of a 52,000-kD protein band from tissue extracts of islets cultured for 7 days in 3, 12, and 30 mM glucose were 25, 44, and 270% compared with that of extract from freshly isolated islets (100%). RNA blot analysis of glucokinase mRNA demonstrated virtually the same levels in fresh islets and islets after 7 days of culture in 3 or 30 mM glucose. The adaptive response of glucokinase to glucose appears therefore to be occurring at a translational or posttranslational site in cultured islets. These data greatly strengthen the concept that glucose is the regulator that induces the activity of glucokinase, which in turn determines the rate change of glucose usage as well as glucose stimulated insulin release from beta-cells. Thus, the hypothesis that glucokinase is the glucose sensor of beta-cells is strengthened further. PMID- 1612195 TI - Association of 24-h cardiac parasympathetic activity and degree of nephropathy in IDDM patients. AB - In insulin-dependent diabetic patients, nephropathy is a predictor of mortality and coronary heart disease. Impaired cardiac vagal function is an important factor in the pathophysiology of sudden cardiac death in coronary heart disease. Autonomic neuropathy in diabetes in particular involves vagal function. Bedside tests and 24-h measurements of cardiac parasympathetic activity were compared in 37 insulin-dependent diabetic patients, and the relationship between 24-h vagal activity and degree of nephropathy was investigated. Nephropathy was classified according to urinary albumin excretion as normoalbuminuria, incipient, and overt nephropathy. Mean age (approximately 30 yr) was not different among groups. The 24-h measurements of parasympathetic activity appeared more sensitive than bedside tests, as 33% of patients without cardiac autonomic neuropathy in bedside tests had 24-h vagal activity values below the 95% confidence limits of 14 healthy control subjects. Patients with incipient or overt nephropathy had significantly lower mean values for vagal activity during both wake and sleep time than healthy control subjects. Increasing degree of nephropathy was associated significantly with increasing attenuation of 24-h vagal activity (P less than 0.001). The covariation of degree of neuropathy and nephropathy may suggest common pathogenetic mechanisms. The reduced 24-h vagal activity, even in the early stages of nephropathy, could be an important risk factor for cardiac death in insulin-dependent diabetic patients. PMID- 1612194 TI - Human islet glucokinase gene. Isolation and sequence analysis of full-length cDNA. AB - Pancreatic islet glucokinase (ATP:D-hexose-6-phosphotransferase) cDNAs were isolated from a human islet cDNA library in lambda-gt11. One clone (hlGLK2), 2723 bp plus additional poly(A) residues, appeared to be full length because its size was consistent with a single 2.9-kb glucokinase mRNA on Northern-blot analysis of islet RNA. This cDNA contained an open reading frame of 1395 bp from an ATG codon at position 459, encoding a predicted protein of 465 amino acids (52,000 M(r)). Comparison of the nucleotide sequences of the human islet glucokinase cDNA with that of the recently isolated human liver glucokinase cDNA revealed that the two cDNAs differed completely on their 5'-ends, followed by an identical 2204-bp overlap extending to the 3'-ends. The 5'-ends of islet and liver glucokinase cDNAs predicted proteins that differ by 15 NH2-terminal residues. The overall sequence identity (70%) between the first exons of the human islet and rat islet cDNAs suggested that the islet promoter regions, like the liver promoter regions, have been conserved through evolution. Thus, NH2-terminal differences for human liver and islet enzymes might be explained by use of alternate promoters between the two tissues, analogous to the NH2-terminal differences of the rat liver and rat islet enzymes. If so, this relationship predicts important tissue-specific regulatory functions of these regions. Variations in the glucokinase gene are likely to occur in humans. Isolation of a human islet glucokinase cDNA has provided the sequence necessary to determine whether these variants are important determinants in the genetic predisposition for diabetes mellitus. PMID- 1612196 TI - Differential expression of retinal insulin receptors in STZ-induced diabetic rats. AB - A major complication of diabetes mellitus is retinopathy, which is characterized by increased neovascularization and neuronal degeneration in the retina. The biochemical processes underlying these changes are largely unknown. To better understand the role(s) of insulin or its lack and the resultant hyperglycemia in the etiology of these events, peripheral and neuronal (having 125 kDa and 115 kDa alpha subunits, respectively) insulin receptor subtype levels in the retinas of Streptozocin-induced diabetic rats were quantified. Immunoblot analysis of wheat germ agglutinin-agarose purified retinal membrane proteins revealed that retinas from diabetic rats expressed higher insulin receptor levels than retinas from control rats. This increase reflected a doubling of neuronal and a approximately 20% decrease in peripheral insulin receptor subtypes, respectively. Insulin treated diabetic rats had neuronal receptor levels equal to control values, at the same time having a further reduced number of peripheral insulin receptors relative to controls. Affinity labeling analysis of WGA-purified retinal membrane proteins indicated a 1.5-fold increase in neuronal and a 9% decrease in peripheral receptor subtypes, corroborating the immunoblot analysis. Neuronal insulin receptors in WGA-purified cortical synaptosomal membranes also were increased in diabetic rats, with insulin treatment reducing this effect. The up regulated receptors retained their ability to undergo insulin-dependent autophosphorylation and, as such, did not appear functionally impaired. These data suggest that the expression of neuronal insulin receptors in retina and brain and peripheral insulin receptors in the retina of diabetic rats is sensitive to levels of insulin/glucose in peripheral circulation. PMID- 1612197 TI - Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels. AB - The relations of regional adipose tissue (AT) distribution measured by computed tomography (CT) to plasma insulin-glucose homeostasis and lipoprotein-lipid levels were studied in 58 obese and 29 lean control men. In the group of obese men, the visceral AT area measured by CT was positively correlated with fasting plasma triglyceride and insulin levels and with glucose and insulin areas under the curves measured during a 75-g oral glucose tolerance test. Visceral AT area was also negatively associated with plasma high-density lipoprotein (HDL) and HDL2 cholesterol levels. The relative accumulation of abdominal fat, estimated by the ratio of abdominal to femoral AT areas obtained by CT, was also a significant correlate of indices of carbohydrate metabolism and was the best univariate correlate of plasma lipoprotein levels. No significant associations were observed between the visceral AT area, the ratio of abdominal to femoral AT areas, and indices of carbohydrate and lipoprotein metabolism in the group of lean men. On the other hand, the subcutaneous abdominal AT area was a significant correlate of the glucose area under the curve in both groups of men, but this association was not independent from the percentage of total body fat. No relationship was observed between the femoral AT area and indices of carbohydrate metabolism in either lean or obese groups. In obese men, however, the femoral AT area was negatively correlated with plasma triglyceride concentration and positively correlated with plasma HDL and HDL2 cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612198 TI - Glucokinase gene is genetic marker for NIDDM in American blacks. AB - Glucokinase (ATP:D-glucose-6-phosphotransferase), expressed exclusively in liver and pancreatic islet beta-cells, catalyzes the first step of glycolysis and acts as glucose sensor and metabolic signal generator in these tissues. The enzyme plays a key role in glucose homeostasis and as such is an excellent candidate for inherited defects predisposing to non-insulin-dependent diabetes mellitus (NIDDM). A compound-imperfect dinucleotide (CA)n repeat element was found approximately 10-kb 3' of the human glucokinase gene on chromosome 7p, which revealed polymorphism with alleles differing in size by 2-15 nucleotides in unrelated individuals. A polymerase chain reaction assay was developed, and genomic DNA from 275 biologically unrelated American black individuals was typed for glucokinase alleles. The differences in allelic frequencies between individuals with NIDDM and nondiabetic individuals were compared. After typing 112 diabetic and 163 nondiabetic subjects, we found five different-sized alleles, with Z defined as the most common allele, Z + 2, Z + 4, Z + 10, and Z - 15. The Z allele was more common in nondiabetic subjects than in diabetic patients (60.4 vs. 49.6%, P = 0.012). The Z + 4 allele was more common in diabetic patients than in nondiabetic subjects (20.1 vs. 12.0%, P = 0.009). After adjusting for age, sex, and body mass index, the Z + 4 allele continued to have a positive association with NIDDM (P = 0.0018), and the Z allele had a negative association with NIDDM (P = 0.0334). The Z + 4 allele, transmitted as an autosomal dominant trait, appeared to be the most significant one at this locus.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612199 TI - Familial clustering of insulin sensitivity. AB - This study's objective was to determine whether there is familial clustering of insulin sensitivity (SI) or insulin-independent glucose uptake (SG), which would be evidence that they are genetically determined traits. Outpatients had a 3-h intravenous glucose tolerance test. Nondiabetic individuals (n = 183), ranging in age from 16 to 60 yr, were from 105 families that had 2 parents with non-insulin dependent diabetes mellitus. Of these families, 62 contributed 1 offspring, 21 contributed 2, 13 contributed 3, 6 contributed 4, and 2 and 1 contributed 5 and 6, respectively. The minimal model of glucose disposal and the glucose and insulin values from the intravenous glucose tolerance tests were used to estimate SI and SG. The intraclass correlation coefficient was used to compare the within family variability of SI and SG with the respective between-family distributions. The intraclass correlation coefficients were 0.26 (P = 0.008) for SI and 0.081 (P = 0.45) for SG. SI and SG were uncorrelated (r = -0.059, P = 0.42). The intraclass correlation of SI could not be explained by familial clustering of fasting insulin or ideal body weight. Finally, the 10 families with the lowest values of SI had a significantly higher within-sibship variability of SI than the other 33 families (P less than 0.001, F test). SI but not SG showed familial clustering, which is consistent with a polygenic determinant of SI. In addition, a large within-family variability of SI in some families is compatible with a major gene effect with a dominant mode of inheritance.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612200 TI - In vivo imaging of insulin receptors in monkeys using 18F-labeled insulin and positron emission tomography. AB - We previously described a prosthetic group methodology for incorporating 18F into peptides and showed that 18F-labeled insulin (18F-insulin) binds to insulin receptors on human cells (IM-9 lymphoblastoid cells) with affinity equal to that of native insulin (1). We now report studies using 18F-insulin with positron emission tomography to study binding to insulin receptors in vivo. Positron emission tomography scans were performed in six rhesus monkeys injected with 0.3 1.4 mCi of 18F-insulin (approximately 0.1 nmol, SA 4-11 Ci/mumol). Integrity of the tracer in blood, determined by immunoprecipitation, was 94% of control for the first 5 min and decreased to 31% by 30 min. Specific, saturable uptake of 18F was observed in the liver and kidney. Coinjection of unlabeled insulin (200 U, approximately 1 nmol) with the 18F-insulin reduced liver and increased kidney uptake of the labeled insulin. Liver radioactivity was decreased by administration of unlabeled insulin at 3 min, but not 5 min, after administration of the tracer, while some kidney radioactivity could be displaced 5 min after injection. Clearance of 18F was predominantly in bile and urine. 18F-insulin is a suitable analogue for studying insulin receptor-ligand interactions in vivo, especially in the liver and kidney. PMID- 1612202 TI - Enhanced glucose tolerance in spontaneously hypertensive rats. Pancreatic beta cell hyperfunction with normal insulin sensitivity. AB - We used intravenous glucose tolerance tests in vivo and 3-O-methylglucose transport into skeletal muscle in vitro to assess glucose tolerance, pancreatic beta-cell function, and insulin action in 9- to 11-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). Body weight was slightly higher in the WKY (P less than 0.001), while blood pressure was elevated in the SHR (P less than 0.001). Insulin responses to intravenous glucose after 4 or 12 h of fasting in SHR were 2-3 times the responses of WKY rats (P less than 0.001). The greater insulin responses in SHR were associated with accelerated glucose disappearance P less than 0.001 vs. WKY rats). A direct correlation (r = 0.49, P less than 0.05) between the peak plasma insulin responses to glucose and Kg values in SHR suggested that the exaggerated insulin responses contributed to the accelerated glucose disappearance in that group. 3-O-methylglucose transport rates into epitrochlearis muscles in vitro did not differ significantly between SHR and WKY groups in the absence of insulin (P less than 0.2) or in the presence of insulin at physiological (600 pM, P greater than 0.4) or pharmacological (120,000 pM, P greater than 0.9) concentrations. Thus, compared with WKY rats, SHR had exaggerated insulin responses to glucose, similar insulin-mediated glucose transport into skeletal muscle, and enhanced glucose tolerance. Our findings indicate that young, hypertensive SHR have hyperfunction of pancreatic beta-cells that is unrelated to insulin resistance. The resultant nutrient-stimulated hyperinsulinemia could play a role in the development or maintenance of elevated blood pressure in SHR. PMID- 1612201 TI - Impaired glucose sensitivity of ATP-sensitive K+ channels in pancreatic beta cells in streptozotocin-induced NIDDM rats. AB - ATP-sensitive K+ channels (KATP channels) are known to play a key role in the cellular mechanism of insulin secretion from pancreatic beta cells. In order to examine the possible impairment of KATP channel function in non-insulin-dependent diabetes mellitus (NIDDM), we have studied the properties of the KATP channels in single beta cells of neonatally streptozotocin-induced diabetic rats (NSZ rats) using the patch-clamp technique. The unitary conductance of the channel in diabetic beta-cells was virtually identical to that in control beta cells and there was no difference in the sensitivity to ATP and glibenclamide of KATP channels between the NIDDM and control groups. In response to glucose, the activity of the KATP channels was diminished in a dose-dependent manner in both control and diabetic cells. However, the inhibition of the KATP channels in beta cells of NSZ rats was significantly less than that in control cells. Even in the presence of 11.1 mM glucose, the openings of a few single KATP channels were consistently observed in cell-attached patch membranes of diabetic, but not control, beta-cells. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells in NSZ rats is associated with a reduced sensitivity of the KATP channel to glucose, but not to ATP, presumably due to a deficiency in glucose metabolism. PMID- 1612204 TI - Treatment of severely diabetic pancreatectomized dogs using a diffusion-based hybrid pancreas. AB - Long-term survival of dog islet allografts implanted in diabetic pancreatectomized dogs was achieved by islet encapsulation inside cylindrical chambers fabricated from permselective acrylic membranes (nominal M(r) exclusion of 50,000-80,000). Dog islets were isolated from the pancreases of outbred mongrel dogs by collagenase digestion. Chambers containing mean +/- SE 316 +/- 63K islet equivalents (mean islet volume, 558 +/- 111 mm3, purity 90-95%) were peritoneally implanted into six totally pancreatectomized dogs. The dogs were monitored for glycemic control by fasting and postprandial blood glucose determinations, and responses to both intravenous glucose (intravenous glucose tolerance test 0.5 g/kg) and oral glucose (oral glucose tolerance test 1 g/kg). All of the dogs required appreciably lower dosages of exogenous insulin therapy for control of fasting blood glucose levels, with the mean daily insulin dose dropping from 38 +/- 7 to 5 +/- 1 U/day during the 1st wk. Three recipients required no insulin for greater than 82, greater than 68, and 51 days. Intravenous glucose tolerance test K values (decline in glucose levels, %/min) at 1 and 2 mo postimplantation were 2.7 +/- 0.4 and 2.0 +/- 0.5, respectively compared with 3.5 +/- 0.5 before pancreatectomy. The glucose values during oral glucose tolerance tests at 2 wk, although returning to less than 125 mg/dl (less than 7.0 mM) by 2 h, exceeded the normal range, with peak values of 174 to 202 mg/dl (9.7 to 11.3 mM). These preliminary results are encouraging, and represent an important step in determining the feasibility of using this type of diffusion based hybrid artificial pancreas as treatment for diabetes mellitus in humans. PMID- 1612203 TI - Genetic marker associations with proliferative retinopathy in persons diagnosed with diabetes before 30 yr of age. AB - It has been suggested that HLA-DR4 is a marker of genetic predisposition to proliferative retinopathy. To investigate this relationship and potential associations between other polymorphic genes and proliferative retinopathy, a sample (n = 428) of participants in the population-based Wisconsin Epidemiologic Study of Diabetic Retinopathy was selected for typing for HLA-A, -B, -C, and -DR and a panel of other polymorphic genes. The presence of proliferative retinopathy was determined from grading of stereoscopic color fundus photographs taken at 2 examinations, 4 yr apart. In logistic regression models with repeated measures, persons with HLA-DR4 who were negative for DR3 were five times more likely to have proliferative retinopathy than those negative for both antigens after adjusting for other potential risk factors (Odds ratio = 5.43, 95% Confidence Interval (Cl) = 1.04, 28.30). HLA-C2, AK-2, and MNSs-S also were associated positively with proliferative retinopathy, and HLA-DR8 was associated inversely with this complication of diabetes in each case before adjusting for the number of comparisons. These data suggest that the genetically determined immunopathic mechanisms leading to diabetes, and in linkage disequilibrium with DR4, may independently contribute to the development of proliferative retinopathy. PMID- 1612205 TI - Stimulation by proinsulin of expression of plasminogen activator inhibitor type-I in endothelial cells. AB - In patients with non-insulin-dependent diabetes mellitus, concentrations in plasma of insulin and its precursors, proinsulin and split proinsulin, are increased. Because increased concentrations of plasminogen activator inhibitor type-1 (PAI-1) occur also, we hypothesized that proinsulin and split proinsulin may augment endothelial cell PAI-1 expression, thereby potentially attenuating endogenous fibrinolysis and accelerating atherosclerosis. Proinsulin increased PAI-1 activity in conditioned media of endothelial cells as did split proinsulin, paralleled by increased expression of PAI-1 mRNA. These effects of proinsulin were not dependent on its conversion to insulin nor on its interactions with the insulin receptor. The proinsulin stimulation of PAI-1 expression was not attenuated by either anti-insulin receptor antibodies or a 100-fold excess of insulin. Furthermore, proinsulin-mediated increases in PAI-1 expression were not inhibited by a 500-fold excess of insulinlike growth factor I. In addition, inhibition of tyrosine kinase, which mediates many of the diverse effects of insulin and insulinlike growth factor I, did not attenuate the effect of proinsulin. These results indicate that proinsulin augments PAI-1 expression, potentially contributing to vasculopathy in patients with non-insulin-dependent diabetes mellitus. PMID- 1612206 TI - The prevalence of cerebral visual disturbance in children with cerebral palsy. AB - Assessment of visual acuity using the visual acuity card procedure in 164 children with cerebral palsy revealed low visual acuity in 71 per cent. Results of ophthalmological examination were available for 74 of these patients, but could not explain adequately the low visual acuity of 36 of the 43 patients (84 per cent) assessed by both the acuity card procedure and other techniques. There is a high probability that cerebral visual disturbance is present in these patients. Awareness of visual disability when compiling a programme of visual and neurodevelopmental stimulation for children with cerebral palsy is essential. PMID- 1612207 TI - A proposed formula for calculating energy needs of children with cerebral palsy. AB - This study compared two methods of calculating the energy needs of children with CP: the traditional method, using RDA for chronological age; and the Krick method, which calculates the BMR and includes factors for muscle tone, movement or level of activity, and energy requirements for normal and catch-up growth. 30 tube-fed children, aged between nine months and 18 years, who were inpatients for longer than one week at the Kennedy Institute, were reviewed. 14 were female. They were weighed at admission and discharge to evaluate the rate of growth; calorie prescriptions at discharge were based on the clinical course. The Krick method was found to be a more potent predictor of the discharge prescription than the RDA method. PMID- 1612208 TI - Infants with myelomeningocele: visual recognition memory and sensorimotor abilities. AB - The cognitive development was explored of 29 infants with myelomeningocele. Although as a group they tended to be less likely to demonstrate visual recognition memory than a matched control group, excluding the more severely cognitively impaired infants from analysis rendered this difference non significant. Infants with myelomeningocele demonstrated more verbal imitation on the Uzgiris-Hunt Assessment Scales than the controls, but there were no statistically significant differences between the groups on the Objects Permanence, Schemes, or Objects in Space subscales. The two groups did not differ on the majority of demographic and environmental variables examined, suggesting that group differences may be due to differences in biomedical variables. However, within the myelomeningocele group, environmental variables correlated with the majority of the cognitive measures, while correlations between cognitive performance and both demographic and biomedical variables were at chance level. PMID- 1612210 TI - Diagnostic criteria for migraine and psychogenic headache in children. AB - The headache histories obtained from 214 children were analysed by computer to see whether it was possible to identify and classify migraine, and to distinguish children with psychogenic headache. During headache attacks, most children had no or very few associated symptoms. For classification, 175 patients were divided into four homogeneous groups; the remaining 39 could not be grouped. An overlap between the different groups was found. Psychogenic headache emerged as a clearly definable syndrome, characterised by psychological problems and daily headache for a period of at least one month (10 patients). When the 214 patients were grouped according to the classification of the Headache Classification Committee of the International Headache Society, distinguishing those children with psychogenic headache was no longer possible. PMID- 1612209 TI - Prognostic reliability of somatosensory and visual evoked potentials of asphyxiated term infants. AB - The purpose of this study was to determine whether SEPs would improve the predictive power of VEPs for the prognosis of asphyxiated infants. 57 term infants had SEPs and VEPs recorded during the first three days of life, during the first week and at follow-up visits. All survivors have been followed for 18 to 24 months. 34 had a normal outcome, 12 had severe neurological sequelae and 11 died. The SEPs had both high sensitivity (96 per cent) and negative predictive power (97 per cent); normal SEPs virtually guaranteed normal outcome. The VEPs had both a specificity and positive predictive power of 100 per cent; abnormal VEPs guaranteed abnormal outcome. Both together had a higher predictive power than either alone. The combination of VEPs and SEPs yields a powerful means of prognostication for term asphyxiated infants; the results suggest that both be included in the assessment of this population. PMID- 1612211 TI - Convulsions with fever as a presenting feature of bacterial meningitis among preschool children in developing countries. AB - The authors report 522 infants and young children aged between one month and six years who presented with convulsions and fever as emergencies in Nigeria. 22 had bacterial meningitis, six of whom lacked the usual signs of meningitis. Although features of complex febrile convulsions were significantly associated with bacterial meningitis, it is concluded that, as an aid to the early diagnosis of bacterial meningitis, all preschool children convulsing with fever in developing countries should have a lumbar puncture. This may reduce the contribution of meningitis to chronic neurological disabilities. The necessity for such a policy is illustrated by a case report of a young infant with convulsions and fever caused by meningitis, seen at a general hospital. PMID- 1612212 TI - The sex ratios of dyslexic children and their sibs. AB - There is a male excess in many samples of patients with dyslexia and related conditions. Various suggestions have been made to account for this, including: (1) ascertainment bias, in that boys are more likely to be referred than girls; (2) a biological propensity of parents of dyslexic children to produce a high proportion of boys (compared with parents of controls); and (3) greater susceptibility among boys than girls to these conditions. These explanations are not mutually exclusive, and the first undoubtedly applies to some clinic samples. This paper offers equivocal evidence for the second explanation, and introduces new evidence for the third. PMID- 1612213 TI - Roberts/pseudothalidomide syndrome and normal intelligence: approaches to diagnosis and management. AB - Roberts/pseudothalidomide syndrome is a rare autosomal recessive disorder, involving growth and mental retardation, midline craniofacial abnormalities and tetraphocomelia. Cytogenetic studies have confirmed reproducible chromosomal abnormalities throughout the syndrome's wide range of clinical presentations. A family with two affected siblings is presented. One child was stillborn; the other, though severely affected by all of the physical characteristics of this disorder, has developed normally both at school and in his social-personal skills. This report supports the idea that Roberts syndrome and pseudothalidomide syndrome are the same condition, and emphasizes that normal intelligence and positive social-personal adjustment are possible, even with all of the stigmata of Roberts syndrome. Aggressive medical intervention is suggested, as well as forthright parental counselling when discussing the possible outcome for these patients. PMID- 1612214 TI - Behavioral treatment of adipsia in a child with hypothalamic injury. AB - Damage to the hypothalamic region is known to affect a wide range of homeostatic and adaptive functions, including water and food regulation, temperature control, hormone secretion and behavior. Deficient thirst is a serious consequence of hypothalamic injury, since water losses are not replaced by drinking. The effectiveness of behavioral procedures in increasing drinking is described for a child with diminished thirst secondary to hypothalamic injury. PMID- 1612215 TI - A female patient with Lesch-Nyhan syndrome. AB - The authors report the second case of a female with typical Lesch-Nyhan syndrome. She exhibited athetoid movement, self-multilation, mental retardation and spasticity. Laboratory investigations revealed hyperuricaemia, hyperuricosuria and decreased erythrocyte hypoxanthine guanine phosphoribosyl transferase activity. She has normal female external genitalia and karyotype. Her parents are non-consanguineous and there is no family member with gout, nephropathy or any psychoneurological disorder. To prevent self-stimulation, it was necessary to fix the patient's upper extremities to the backrest of her wheelchair. The authors also describe an apparatus that limits elbow flexion. PMID- 1612216 TI - Cerebral palsy epidemiology: where are we now and where are we going? PMID- 1612217 TI - Submandibular duct retroposition reduces drooling, but may cause caries in lower front teeth. PMID- 1612218 TI - The influence of clothes and bedclothes on infants' gross motor development. PMID- 1612220 TI - Report from the 11th Workshop of Artificial Insulin Delivery Systems, Pancreas and Islet Transplantation Study Group of the EASD (AIDSPIT). PMID- 1612219 TI - Temporal-lobe structures and autism. PMID- 1612221 TI - The link between hyperglycaemia and diabetic nephropathy. AB - A large number of experimental studies in animals and retrospective or non randomised prospective studies in humans provide support for the concept that the microvascular complications of diabetes mellitus are dependent on hyperglycaemia. This review focuses on four potential biochemical pathways linking hyperglycaemia to changes within the kidney which can plausibly be linked to the functional and structural changes characterising diabetic nephropathy. These four pathways are the polyol pathway, non-enzymatic glycation, glucose autoxidation and de novo synthesis of diacylglycerol leading to protein kinase C and phospholipase A2 activation. Rather than being independent, there are several potential interactions between these four pathways which may explain confusing and overlapping effects observed in studies examining inhibitors of individual pathways. As many of the steps which follow on glucose metabolism are subject to modification by dietary and pharmacological means, the further delineation of the pathogenetic sequence leading to tissue damage in diabetes should allow a logical and effective approach to the prevention or treatment of the complications of diabetes. PMID- 1612222 TI - Preservation of the anomeric specificity of glucose-induced insulin release in partially pancreatectomized rats. AB - Attenuation, suppression or even inversion of the normal preference of glucose stimulated insulin release for the alpha-anomer of the hexose was recently proposed to represent a feature of Beta-cell glucotoxicity in Type 2 (non-insulin dependent) diabetes mellitus. Since recent reports emphasize the possible significance of Beta-cell secretory hyperactivity as a determinant of such a glucotoxicity, the anomeric specificity of glucose-induced insulin release was examined in normoglycaemic partially pancreatectomized rats. About 80-85% of the pancreas was removed, the animals then being given sucrose via their drinking water up to the time of killing. In these animals, alpha-D-glucose was more efficient than beta-D-glucose in stimulating insulin release from the perfused pancreas, the alpha/beta ratio in insulin output not being significantly different from that found in control rats. It is concluded, therefore, that the anomeric malaise, taken as a manifestation of Beta-cell glucotoxicity, it attributable to hyperglycaemia rather than to Beta-cell secretory hyperactivity. PMID- 1612223 TI - Regionally disturbed production of cartilage proteoglycans in malformed fetuses from diabetic rats. AB - Fetuses from normal and manifestly diabetic rats were obtained on pregnancy day 20. The fetuses from the diabetic rats were of normal or malformed morphology. Three tissue groups were dissected free; costal cartilage, the hard tissue of the rear, and of the frontal portion of the mandible. These tissues were maintained in vitro for 24 h during which time they were labelled with [35S]sulphate. After the culture period the tissues were extracted with guanidine HCl and the resulting residues were further extracted with alkali. The culture medium was saved and its macromolecular content was compared to that of the extracts. The proteoglycans recovered in all extracts eluted at two distinct positions after chromatography on a Sepharose CL-2B column (peak I: Kav approximately 0.4, and peak II: Kav approximately 0.8), but the elution patterns were markedly different in extracts from various tissues. Thus, in rib cartilage, the majority of the labelled proteoglycans were located in peak I (approximately 90%) with no difference between extracts of fetuses from normal and diabetic pregnancies. In extracts of mandibular cartilaginous tissue from normal rat offspring the peak I percentage (60-80%) was lower than in the rib cartilage extracts. In the extracts from the frontal portion of malformed mandibles of fetuses of diabetic rats, the peak I percentage (35 +/- 21%) was the lowest of all recorded and the only one to significantly differ from the other percentages in its (the frontal mandible) group. The results show an association between a congenital malformation, micrognathia, and a disturbance in the production of chondroitin sulphate proteoglycans in the malformed region. PMID- 1612224 TI - Oral vanadate decreases muscle insulin resistance in obese fa/fa rats. AB - Oral vanadate has been reported as improving glucose homeostasis in genetically obese and hyperinsulinaemic fa/fa rats. It has also been shown that these beneficial effects could not be ascribed to the decrease in body weight induced by the treatment, or to changes in insulin counterregulatory hormones. The present study examined therefore whether the effects of vanadate could be attributed to a direct correction of the severe insulin resistance of these animals. fa/fa Rats chronically treated with vanadate were compared to both control rats fed ad libitum and pair-fed rats. The three groups were studied in the basal state and during euglycaemic hyperinsulinaemic clamps. Slightly lower plasma glucose levels were always maintained in vanadate-treated rats in conjunction with markedly lower plasma insulin levels either during basal or clamp studies. During the clamp, the glucose infusion rate required to maintain glycaemia at basal values was consistently higher in vanadate-treated rats than in the other two groups. Experiments using [6-3H]glucose as tracer showed that this was not due to a greater inhibition of hepatic glucose production by insulin, but corresponded to a larger increment in peripheral glucose disposal. The stimulation of overall glucose metabolic clearance induced by insulin was 129% and 41% higher in vanadate-treated than in control and pair-fed rats respectively. Similar experiments with 2-deoxy-[1-3H]glucose as tracer showed that the larger increase in insulin-mediated glucose clearance occurred in various types of muscle. The action of insulin was particularly impressive on the cardiac muscle of vanadate-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612225 TI - A high linear growth is associated with an increased risk of childhood diabetes mellitus. AB - Insulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recent-onset diabetic children, 0-14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to 1 years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values less than 0; 0-1 and greater than 1, respectively; p = 0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612226 TI - Hyperinsulinaemia in youth is a predictor of type 2 (non-insulin-dependent) diabetes mellitus. AB - This study aimed to compare plasma insulin concentrations across the age-range from childhood to old age in the populations of Nauru and Tuvalu, and to assess their relationship to the incidence of impaired glucose tolerance and diabetes in young Nauruans. The studies, performed in 1975 and 1976, found that Nauru had a higher prevalence of Type 2 (non-insulin-dependent) diabetes mellitus than Tuvalu. Both studies included subjects of 8-29 years of age (n = 320 in Nauru, n = 318 in Tuvalu) and on these subjects glucose tolerance status, body mass index and fasting and 2-h (post 75 g glucose load) plasma insulin concentrations were determined. In Nauru, follow-up surveys in 1982 and 1987 included many of the subjects first seen in 1975/1976, allowing the incidence and natural history of glucose intolerance to be studied. Within the group of subjects with normal glucose tolerance, there was no effect of age on plasma insulin distributions in either population. However, in both populations, 8-19 year old subjects with normal glucose tolerance had higher body mass index-adjusted geometric mean fasting and 2-h insulin concentrations than older age-groups (p less than 0.001 for fasting insulin). Body mass index-adjusted geometric mean 2-h plasma insulin was higher in subjects with abnormal glucose tolerance relative to those with normal glucose tolerance in both populations. In Nauruans, 2-h insulin levels at baseline were predictive of impaired glucose tolerance and Type 2 diabetes in 1982, and fasting and 2-h insulin levels predicted development of Type 2 diabetes in 1987.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612227 TI - Contrasting metabolic effects of continuous and pulsatile growth hormone administration in young adults with type 1 (insulin-dependent) diabetes mellitus. AB - Plasma growth hormone profiles in adolescents with Type 1 (insulin-dependent) diabetes mellitus are characterized by both increases in pulse amplitude and higher baseline concentrations. To determine which of these abnormalities adversely affect metabolic control, we studied six young adults overnight on three occasions. On each night somatostatin (50-100 micrograms.m2-1.h-1) and glucagon (1 ng.kg-1.min-1) were infused continuously and 18 mU/kg of growth hormone was given as either: three discrete pulses of 6 mU.kg-1.h-1 at 180-min intervals or a 12-h infusion (1.5 mU.kg-1.h-1) or buffer solution only on a control night. Euglycaemia was maintained by an insulin-varying clamp. Blood samples were taken every 15 min for glucose and growth hormone and every hour for intermediate metabolites and non-esterified fatty acids. Comparable normoglycaemic conditions were achieved on all three nights. Growth hormone levels achieved (mean +/- SEM) on study nights were: 32.8 +/- 2.2 mU/l (peak level during growth hormone pulses); 9.8 +/- 0.8 mU/l (continuous growth hormone) and 1.1 +/- 0.3 mU/l (control level). Pulsatile growth hormone administration led to an increase in insulin requirements (mean +/- SEM: 0.17 +/- 0.03 vs control 0.09 +/- 0.01 mU.kg-1.min-1, p less than 0.05) whereas insulin requirements following continuous growth hormone administration were unchanged. Cross correlation confirmed an increase in insulin requirements occurring 135 min after a growth hormone pulse (r = 0.21, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612228 TI - Antibodies to the M(r) 64,000 (64K) protein in islet cell antibody positive non diabetic individuals indicate high risk for impaired beta-cell function. AB - A prospective study of a normal childhood population identified 44 islet cell antibody positive individuals. These subjects were typed for HLA DR and DQ alleles and investigated for the presence of antibodies to the M(r) 64,000 (64K) islet cell antigen, complement-fixing islet cell antibodies and radiobinding insulin autoantibodies to determine their potency in detecting subjects with impaired Beta-cell function. At initial testing 64K antibodies were found in six of 44 islet cell antibody positive subjects (13.6%). The same sera were also positive for complement-fixing islet cell antibodies and five of them had insulin autoantibodies. During the follow-up at 18 months, islet cell antibodies remained detectable in 50% of the subjects studied. In all six cases who were originally positive, 64K antibodies were persistently detectable, whereas complement-fixing islet cell antibodies became negative in two of six and insulin autoantibodies in one of five individuals. HLA DR4 (p less than 0.005) and absence of asparic acid (Asp) at position 57 of the HLA DQ beta chain (p less than 0.05) were significantly increased in subjects with 64K antibodies compared with control subjects. Of 40 individuals tested in the intravenous glucose tolerance test, three had a first phase insulin response below the first percentile of normal control subjects. Two children developed Type 1 (insulin-dependent) diabetes mellitus after 18 and 26 months, respectively. Each of these subjects was non-Asp homozygous and had persistent islet cell and 64K antibodies.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612229 TI - von Willebrand factor and early diabetic retinopathy: no evidence for a relationship in patients with type 1 (insulin-dependent) diabetes mellitus and normal urinary albumin excretion. AB - High plasma levels of von Willebrand factor, an indicator of endothelial cell dysfunction, have been reported in both diabetic retinopathy and nephropathy. It is unclear, however, whether von Willebrand factor is related to diabetic retinopathy in the absence of diabetic nephropathy. The relationship between retinal status and plasma von Willebrand factor concentration was investigated in a cohort of 17 patients with Type 1 (insulin-dependent) diabetes mellitus who were followed-up for a median of 42 months. The patients were examined three times. They were selected for having had normal urinary albumin excretion and no evidence of retinopathy (on fundoscopy) at the first and second examination. They were then divided into two groups, according to absence (Group A; n = 9) or presence (Group B; n = 8) of retinopathy on fundoscopy or fluorescein angiography at the third examination. Urinary albumin excretion remained normal in all patients. Plasma von Willebrand factor levels were similar in both groups: (median) 128 vs 123%, 164 vs 132% and 159 vs 130% (first, second and third examination, respectively). Median changes in plasma von Willebrand factor were also similar: +7 vs +9% and +5 vs +1% (first-second and second-third examination). Patients in whom the plasma von Willebrand factor concentration increased had higher systolic blood pressure at the third examination (150 +/- 30 vs 130 +/- 12 mmHg, p = 0.02) when compared to those in whom plasma von Willebrand factor did not increase, but were of similar age and had similar diabetes duration, retinal status, diastolic blood pressure, glycated haemoglobin and serum cholesterol concentration.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612230 TI - The reproducibility and sensitivity of sural nerve morphometry in the assessment of diabetic peripheral polyneuropathy. AB - The nerve fibre loss, atrophy and injury of diabetic peripheral polyneuropathy and their responses to metabolic intervention have been studied by morphometric analysis of sural nerve biopsies. The magnitudes and sources of intra- and inter individual variation in these morphometric measures have not been investigated previously in a systematic manner. Morphometric parameters of nerve fibre damage were measured in four separate fascicles from bilateral sural nerve specimens obtained post-mortem from 13 diabetic and 13 non-diabetic subjects. Intra- and inter-individual coefficients of variation were computed and compared to the magnitude of the differences between normal and diabetic subjects. Several morphometric variables emerged as highly sensitive and reproducible measures of nerve fibre damage suitable for clinical studies of diabetic peripheral polyneuropathy. These observations provide a rational basis for the design of future clinical trials employing morphometric end-points. PMID- 1612231 TI - Glutamic acid decarboxylase (GAD) autoantibodies are additional predictive markers of type 1 (insulin-dependent) diabetes mellitus in high risk individuals. AB - The prevalence of glutamic acid decarboxylase autoantibodies was determined with an immunotrapping enzyme activity assay in newly-diagnosed Type 1 (insulin dependent) diabetic patients as well as in first-degree relatives using rat brain homogenate as a source of glutamate decarboxylase. Twenty-six out of 86 islet cell cytoplasmic auto-antibody positive and one out of 24 islet cell autoantibody negative patients of recent onset, had autoantibodies to glutamate decarboxylase above the upper 99% confidence limit obtained from 89 control sera. Among 27 islet cell autoantibody positive relatives including 19 siblings and 8 parents, antibodies to glutamate decarboxylase were found in 8 of 9 (89%) relatives and 7 of 8 (87.5%) siblings with islet cell auto-antibody titres above 20 JDF units, in 1 of 19 (5.2%) relatives with islet cell autoantibody titres between 2 and 5 JDF units, in 2 of 263 (0.7%) siblings and 1 of 139 parents without islet cell autoantibodies. In first-degree relatives, high titre islet cell autoantibodies and autoantibodies to glutamate decarboxylase were tightly associated (X2 = 182, p = 0.0001). None of the relatives with low genetic risk (n = 64), i.e. HLA different to the diabetic proband, was found to be antibody positive. Antibodies to glutamate decarboxylase were present only in those relatives sharing at least one haplotype with the diabetic proband, including two islet cell autoantibody negative but HLA-identical siblings. Autoantibodies to glutamate decarboxylase were present in 7 of 9 (77%) relatives who developed the disease, including one islet cell autoantibody negative sibling.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612232 TI - Islet cell antibodies in normal French schoolchildren. AB - Islet-cell antibodies have been reported to be of predictive value for the future development of Type 1 (insulin-dependent) diabetes in first degree relatives of diabetic patients with the risk increasing in these subjects with the islet-cell antibodies titre. However, very little is known about islet-cell antibodies in background populations. Sera (n = 8363) from schoolchildren (6-17 years) in the French background population were screened for the presence of islet-cell antibodies by the indirect immunofluorescence technique. Islet-cell antibodies greater than 4.5 Juvenile Diabetes Foundation units were found in 150 sera (prevalence rate 1.8%; 95% confidence interval 1.5-2.1%). Only 17 sera demonstrated islet-cell antibody titre greater than or equal to 24 JDF units. No particular feature was found to be significantly different between islet-cell antibody-positive and islet-cell antibody-negative children (age, family history of diabetes, fasting plasma glucose, insulin autoantibodies). A second blood sample was obtained from 80 of 150 islet-cell antibody positive children after a mean interval of 8 months. Only 11 sera became less than 4.5 JDF units with islet cell antibody titres being stable in the remaining sera, including the high-titre positive sera (greater than or equal to 24 JDF units). HLA-DQB typing was performed by restriction mapping techniques in 80 islet-cell antibody-positive, in 93 islet-cell antibody-negative and in 213 Type 1 diabetic children. The distribution of the susceptibility alleles (DQB1-Asp57-negative) was not significantly different between islet-cell antibody-positive and islet-cell antibody-negative children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612234 TI - [Beta-endorphin response during physical exertion with varying degrees of motivation]. PMID- 1612233 TI - Susceptibility to type 1 (insulin-dependent) diabetes mellitus in Spanish patients correlates quantitatively with expression of HLA-DQ alpha Arg 52 and HLA DQ beta non-Asp 57 alleles. AB - HLA-DQ alpha and beta alleles were chosen as the most sensitive Type 1 (insulin dependent) diabetes mellitus susceptibility markers for evaluating the disease associations and Type 1 diabetes risk in a population-based registry from Madrid. The absence of aspartic acid in position 57 of the DQ beta chain (non-Asp 57), and the presence of arginine in position 52 of the DQ alpha chain (Arg 52) were found to be reliable markers of Type 1 diabetes susceptibility among the Spanish population, with significantly higher frequencies among the cases of Type 1 diabetes compared to randomly selected non-diabetic control subjects from the general Madrid population. While non-Asp 57 homozygosity conferred an absolute risk of 32.3 per 100,000 per year and Arg 52 of 31.5 per 100,000 per year, the risk for double homozygotes for both non-Asp 57 and Arg 52 was estimated as 101.7 per 100,000 per year. Individuals homozygous for only one of these alleles, and heterozygous at the other locus, had a markedly lower Type 1 diabetes risk (12.8 per 100,000 per year), approximating the general population incidence for Madrid. Thus, susceptibility to Type 1 diabetes in Spanish patients is associated, quantitatively, with non-Asp 57 DQ beta and Arg 52 DQ alpha alleles. PMID- 1612235 TI - [Sphygmographic parameters of human blood circulation during emotional stress and relaxation]. PMID- 1612236 TI - [Interrelationship between respiration and blood circulation in young people during psychoemotional stress caused by examination situations]. PMID- 1612237 TI - [Evaluation of the relaxation of the myocardial left ventricle in ischemic heart disease and arterial hypertension]. PMID- 1612238 TI - [Comparative evaluation of cardiovascular system reactivity in patients with borderline arterial hypertension and the early stages of essential hypertension]. PMID- 1612239 TI - [Integral assessment of cardiac activity based on a symmetrical approach to EKG analysis]. PMID- 1612240 TI - [Effect of the trace element fluorine on the adaptive response of the heart during exposure of the body to cold]. PMID- 1612241 TI - [Incretory function of the pancreas depending on sex]. PMID- 1612243 TI - [The human factor in controlling economic development (psychophysiologic aspects]. PMID- 1612242 TI - [Response of the cardiorespiratory system to vestibular stimulation in young schoolchildren]. PMID- 1612244 TI - [Adaptive modification of diurnal rhythms of the physiologic functions in children as result of swimming in infancy]. PMID- 1612246 TI - [Patterns in the formation of psychophysiologic functions in schoolchildren aged 12-14]. PMID- 1612245 TI - [Differentiated training of students in grades I-XI, their working capacity and organization of the regimen of academic activity]. PMID- 1612247 TI - [Testing of human visual-motor coordination based on mechanical contour tracking]. PMID- 1612248 TI - [Directed attention and auditory evoked potentials]. PMID- 1612250 TI - [Information support of research and development in the field of psychophysiologic optimization of labor]. PMID- 1612251 TI - [Use of trainers for diagnosing functional disorders and for restoration of professional fitness for work]. PMID- 1612249 TI - [Heart rate changes as a result of slow manipulatory movements]. PMID- 1612252 TI - [Adaptation of operators to sleep deprivation: analysis of brain biopotential dynamics and behavioral parameters]. PMID- 1612253 TI - [Transition from command to market economy and problems of the physiology of labor]. PMID- 1612255 TI - [Analysis of the scales used for measurement of galvanic skin responses in man]. PMID- 1612254 TI - [Study of regulatory mechanisms in operators during a regimen of continuous activity by means of recording lateral leading eye movements]. PMID- 1612256 TI - [Adaptation to high altitude and physical working capacity]. PMID- 1612257 TI - [Neurodynamic parameters of the effectiveness of human adaptation to high altitude]. PMID- 1612258 TI - [Anisotropy and asymmetry of visual perception of a moving stimulus]. PMID- 1612259 TI - [Correlational structure of evoked responses of neurons in the human brain during categorization of visual images]. PMID- 1612260 TI - [Rapid assessment of the functional state of the body by psycholinguistic tests]. PMID- 1612261 TI - [Automated evaluation of adaptive potentials of the body in humans with different morphotypes]. PMID- 1612262 TI - [Mechanism of tympanic temperature reduction at the beginning of muscle work]. PMID- 1612263 TI - [Morphologic and physiologic parameters of thermal adaptation dynamics]. PMID- 1612264 TI - [Diurnal and hourly dynamics of temperature in patients with heart disease]. PMID- 1612265 TI - [Comparison of expected and actual lipid levels in healthy people and patients with ischemic heart disease]. PMID- 1612266 TI - [Interrelationship of the intensity of adaptation mechanisms and immunity parameters in workers performing mental work]. PMID- 1612267 TI - [Lipoprotein and hormonal changes in rowers as a result of six months of training]. PMID- 1612269 TI - [Phase analysis of vascular thermoregulatory reactions during a pressor-cold test]. PMID- 1612268 TI - [Assessment of the diagnostic information valve of amplitude characteristics of the foot arterial pulse]. PMID- 1612270 TI - [Changes in cardiac rhythm of a human operator during simulation of a successful monotonic target tracking and failures]. PMID- 1612271 TI - [Human response to "word associations" and "trained tests"]. PMID- 1612272 TI - [Functional state of the central nervous system in patients with bronchial asthma]. PMID- 1612273 TI - [Dynamics of thyroid function parameters during adaptation of the body to prolonged psycho-emotional and physical stress]. PMID- 1612274 TI - [Altered states of consciousness during treatment of neurotic disorders (attempt to use holotropic breathing methods)]. PMID- 1612275 TI - [Physiologic parameters obtained using an automated complex of the "Filter" type]. PMID- 1612276 TI - [Effect of pulmonary physical parameters on the flow-volume curve of forced expiration]. PMID- 1612277 TI - [Respiratory moisture loss in people with various degrees of adaptation to physical exercise]. PMID- 1612278 TI - [Interhemispheric functional relationship in the process of solution of a visual spatial task]. PMID- 1612279 TI - [Prediction of operators' working capacity using the method of multivariate statistical analysis]. PMID- 1612280 TI - [Dependence of physiologic value and efficiency of simultaneous activity of test pairs on their biorhythm compatibility]. PMID- 1612281 TI - [Temperature adaptation studies in various ecologic conditions]. PMID- 1612282 TI - [Disorders of cerebral hemodynamics in acute Alpine disease]. PMID- 1612283 TI - [Use of thermal sensitivity for assessment of the human functional state]. PMID- 1612284 TI - [Measurement of thermal radiation of the human body in the radiofrequency band]. PMID- 1612285 TI - Monitoring the environment. PMID- 1612286 TI - Women bioscientists in the 1990s. PMID- 1612287 TI - Supramolecular organization of extracellular matrix glycosaminoglycans, in vitro and in the tissues. AB - Connective tissues maintain shape against external and internal stress. They are molecular hierarchies in which fundamental building units come together in tiers of increasing complexity and mutual interactions, based on information carried in the precursor molecules secreted by cells. The collagen fibril is the end product of well-understood self-aggregation controlled by its amino acid sequences, but the interfibrillar amorphous ground substance has not hitherto been seen as structured by analogous aggregations prescribed by the primary structures of the characteristic glycosaminoglycans dissolved therein. Transmission electron microscopy with morphometry and stereology has demonstrated their existence in tissues. Nuclear magnetic resonance defined their secondary structures, rotary shadowing electron microscopy delineated their aggregates in vitro, and molecular dynamics stimulations showed how the latter can spring from the former. The driving forces to aggregation are hydrophobic and hydrogen bonding, offset by electrostatic repulsion between polyanionic charges. The relative stabilities of the aggregates are determined by this balance, and hence by the position and number of their charges, particularly the sulfate ester groups. Corneal stroma is a system of collagen fibrils, highly ordered to ensure transparency, in which glycosaminoglycan aggregates are suggested to determine the ordered spacing as yardsticks in a way that has parallels in all connective tissues. PMID- 1612288 TI - Mediators of communication and adaptation in the neuroendocrine and immune systems. AB - Bidirectional interactions between the immune and neuroendocrine systems influence specifically physiological activities as diverse as tissue localization of lymphocytes, antibody responses, hypothalamic-pituitary hormone secretion, and neural signal transmission. Our understanding of intersystem communications has been increased by the delineation of the innervation of immune organs, effects of neuromediators on immune cells, and neuroendocrine responses to individual immune cytokines. Two patterns of responses to neuroimmune mediators have been defined to distinguish between direct alterations in cellular function and the more complex states of differentiation and adaptation that condition the threshold and nature of reactions to subsequent stimuli. Recent identification of the molecular mechanisms of action of neuroimmune mediators is exemplified by elucidation of the requirement for prolactin in T lymphocyte proliferation and of the effects of vasoactive intestinal peptide on B lymphocyte expression of adherence proteins. Further knowledge of the advantages of multisystem integration of functions in host defense may reveal other novel mechanisms of cellular communication and biological adaptation. PMID- 1612289 TI - Endothelin-converting enzymes. AB - The putative endothelin-converting enzyme (ECE) has been the focus of intense research, both within academia and the pharmaceutical industry. Interest in ECE stems mainly from the hypothesis that development of inhibitors of ECE will provide an effective means of preventing production of endothelin in circumstances where it may play a pathogenic role. Both an aspartic and a metalloprotease have been identified that have characteristics of this putative enzyme. Evidence suggests that the metalloprotease, which is inhibited by phosphoramidon, may be the physiologically relevant converting enzyme. However, it remains to be demonstrated conclusively that any inhibitor of an ECE activity directly alters endogenous endothelin production and/or the pathogenesis of a disease condition in which endothelin is thought to play a primary role. PMID- 1612290 TI - Lymphocytes and low-frequency electromagnetic fields. AB - Human lymphocytes have been used by several researchers to investigate the biological effect of electromagnetic fields (EMF). EMF modulate the response by lymphocytes to lectin stimulation. The size and direction of the effect depends both on the lymphocyte physiology and on the physical parameters characterizing the EMF. Lymphocytes have also been used to investigate the genotoxicity of EMF exposure. PMID- 1612291 TI - Regulation of antioxidant enzymes. AB - Free radicals generated by a partial reduction of O2 pose a serious hazard to tissues and vital organs, especially membrane lipids, connective tissues, and the nucleic acids of cells. For protection, enzymes have evolved that specifically attack O2-, hydrogen, and organic peroxides, and repair any damage incurred to DNA. With few exceptions, antioxidant enzymes are found in all aerobic and aerotolerant anaerobic organisms. Logic assumes that a basal level of antioxidant enzyme activity is maintained at all times. This may be true. Yet cells must have ways to amplify antioxidant enzyme activity to counter sudden increases in oxygen metabolites. The full details of that regulation are slowly coming to light. Bacteria possess a series of elaborate and interacting genes that can sense specific increases in intracellular H2O2 and O2-. In higher organisms, hormones and metal ion cofactors impose pre- and posttranslational control over the genetic expression of antioxidant enzymes. Furthermore, aging, cellular differentiation, and organ specificity must also be factored into the final equation in higher organisms. This review will discuss some of the more recent findings relevant to antioxidant enzyme regulation in bacteria and higher organisms. PMID- 1612292 TI - Pertussis toxin and target eukaryotic cells: binding, entry, and activation. AB - Pertussis toxin, a protein virulence factor produced by Bordetella pertussis, is composed of an A protomer and a B oligomer. The A protomer consists of a single polypeptide, termed the S1 subunit, which disrupts transmembrane signaling by ADP ribosylating eukaryotic G-proteins. The B oligomer, containing five polypeptides, binds to cell receptors (most likely containing carbohydrate) and delivers the S1 subunit. Current knowledge suggests that expression of ADP-ribosyltransferase activity in target eukaryotic cells arises after 1) nucleotides and membrane lipids allosterically promote the release of the S1 subunit; and 2) the single disulfide bond in the S1 subunit is reduced by reductants such as glutathione. This model suggests conditions for the proper use of the toxin as an experimental reagent. PMID- 1612293 TI - The renewal and differentiation of hemopoietic stem cells. AB - Blood-forming tissues are organized in well-defined microenvironments composed of hemopoietic cells and a supportive stroma of connective tissue and endothelium. Hemopoietic cells segregate to various lineages, all derived from a small population of pluripotent stem cells residing in the bone marrow. Regulation of growth and differentiation, particularly under conditions of perturbations, damage, and disease, is mediated by inducer colony-stimulating factors and interleukins counteracted by inhibitory cytokines. Whereas much is known about the mode of induction of differentiation, insufficient information is available to explain the process of stem cell renewal that is crucial for the longevity of the hemopoietic system. It is also only partially known how inhibition of hemopoietic processes occurs, and what molecules in blood-forming tissues signal organization into discrete patterns. This paper reviews recent progress that has opened new avenues to a better understanding of this highly complex issue. PMID- 1612294 TI - Does chemically induced hepatocyte proliferation predict liver carcinogenesis? AB - Cell proliferation has long been recognized as having an important role in chemically induced carcinogenesis. Based on findings that certain nongenotoxic chemical carcinogens induced cell proliferation in the same organ that had an increased incidence of tumors, it has been hypothesized that a chemically induced response of enhanced DNA synthesis and cellular division causes cancer by increasing the rate of spontaneous mutations. It was further suggested that there would be no increased human risk of cancer by non-DNA-reactive compounds at doses that do not cause a proliferative response. An evaluation of the literature on the relationship between chemically induced cell proliferation and liver carcinogenesis reveals that very few systematic cell proliferation studies have been conducted over periods of extended exposure, and in many cases the exposure concentrations were not similar to those used in the cancer studies. The proliferative response resulting from exposure to many nongenotoxic carcinogens is not well sustained, whereas the carcinogenic response by these chemicals often requires prolonged exposure. The available literature leads to the conclusion that quantitative correspondences between cellular proliferation and carcinogenic responses have not been demonstrated and do not support the hypothesis that chemically induced cell proliferation is the primary mechanism by which nongenotoxic chemicals cause liver cancer. Studies of liver carcinogenesis in two stage models point out the need to better understand chemical effects on cell loss as well as on cell replication, and demonstrate that measurements of cell proliferation alone are not sufficient to elucidate mechanisms of tumor development. PMID- 1612295 TI - Role of primary response genes in generating cellular responses to growth factors. AB - Cellular responses to growth and differentiation factors involve a complex cascade of signals that begins at the cell surface, traverses the cytoplasm, and eventually enters the nucleus. Although a great deal is known about the surface and cytoplasmic stages of this cascade, the nuclear events involved in transducing and translating growth and differentiation signals are less well understood. Recent work has implicated a set of genes known as primary response genes as critical for this process. To propagate the activation signal, these genes possess the ability not only to directly respond to upstream biochemical events, but also to transmit the signal downstream by modulating the unique changes in gene expression necessary for a particular cellular response. In this review we discuss how transcription factors encoded by primary response genes may be responsible for regulating tissue- or stimulus-specific responses associated with cellular activation. PMID- 1612296 TI - Targeted accumulation of polyethylene glycol-coated immunoliposomes in infarcted rabbit myocardium. AB - The less than optimal accumulation of immunoliposome-associated reagents at target sites has often been attributed to the rapid in vivo clearance of immunoliposomes from the blood. In an attempt to overcome the drawback of rapid clearance and use the targeting potential of immunoliposomes, we have prepared long-circulating, 111In-labeled immunoliposomes. Targeting properties and enhanced circulation times were demonstrated in a rabbit model of acute experimental myocardial infarct. The specificity of liposomes for newly exposed intracellular cardiac myosin at the necrotic sites was achieved by incorporating monoclonal antimyosin antibody. Extended circulation times were achieved by cocoating the antimyosin-liposomes with polyethylene glycol (PEG). The half-life of the immunoliposomes was 40 min, which increased to 200 min with 4% mol PEG and to approximately 1000 min with 10% mol PEG. The degree of binding of modified immunoliposomes at the target sites was also dependent on the concentration of PEG incorporated at the liposome surface. This study demonstrates the accumulation of long-circulating targeted liposomes at the area of acute rabbit experimental myocardial infarction. PMID- 1612297 TI - Regulation of phosphatidic acid phosphohydrolase activity during stimulation of human polymorphonuclear leukocytes. AB - Phosphatidic acid phosphohydrolase (PPH) activity was determined in human polymorphonuclear leukocytes (PMNs) by measuring the hydrolysis of [32P]phosphatidic acid (PA) added to cell sonicates. Enzyme activity was localized primarily to a soluble fraction. Soluble and particulate activities required magnesium and were inhibited by calcium, N-ethylmaleimide, sphingosine, and propranolol. The activity in unstimulated PMNs was 0.64 +/- 0.11 nmol of PA hydrolyzed.mg protein-1.min-1 in particulate and 4.20 +/- 0.42 in soluble fractions. Stimulation of PMNs with 1 microM f-Met-Leu-Phe (FMLP) for 10 min caused a slight decrease in soluble activity and a small increase in the activity of particulate fractions. Preincubation with 10 microM cytochalasin B for 5 min before FMLP stimulation markedly enhanced both of these changes. The effect of FMLP plus cytochalasin B was rapid (less than 10 s), whereas the calcium ionophore A23187 (1 microM) and phorbol myristate acetate (100 ng/ml) caused slower and smaller changes in enzyme activity. These results indicate that after chemoattractant stimulation; PPH activity decreases in the soluble fraction and increases in the particulate fraction suggesting that PPH may participate in signal transduction in the PMN. PMID- 1612298 TI - Management of diffuse esophageal spasm with balloon dilatation. AB - Of 1200 patients referred to the esophageal laboratory at Guy's Hospital for investigation of suspected esophageal motility disorders, 61 (5.1%) were diagnosed as diffuse esophageal spasm. Twenty of these patients whose symptoms were severe did not respond to conservative treatment and were treated by balloon dilatation. Results were good in 14 and poor in six patients, which included one esophageal perforation. Diffuse esophageal spasm was diagnosed where more than 30% nonperistaltic activity was demonstrated by manometry. Lower esophageal sphincter pressure and relaxation were normal in all cases except one. Gastroesophageal reflux was present in four of five poor responders who were examined by 24-h ambulatory pH monitoring, and in only one of 10 good responders. Three of the six patients in whom balloon dilatation was successful proceeded to full-length myotomy, with relief of symptoms in two. The indications for, and results of, balloon dilatation in this condition are discussed, and a new radiological sign is described. PMID- 1612299 TI - Pseudotumoral paraesophageal varices. AB - We report a case of paraesophageal varices presenting as a posterior mediastinal mass in a patient with long-standing portal hypertension. These collaterals were present, despite multiple previous sclerotherapies for submucosal esophageal varices and no endoscopic evidence of their recurrence. PMID- 1612300 TI - Comparison of L-hyoscyamine, glucagon, and placebo for air-contrast upper gastrointestinal series. AB - Previous studies have compared the use of anticholinergic drugs and glucagon for upper gastrointestinal (UGI) radiography. Many radiologists prefer glucagon because these comparisons showed it to have a shorter duration of action with fewer side effects. L-Hyoscyamine is the levo-rotatory form of atropine with minor adverse side effects. This study compared the effects of glucagon (N = 48), L-hyoscyamine (N = 43), and placebo (N = 45) on gastric and duodenal distension, mucosal coating, and patient tolerance. L-Hyoscyamine provided gastric and duodenal images equal in quality to glucagon. Except for the more frequent reporting of dry mouth with L-hyoscyamine, side effects were not different among the groups. L-Hyoscyamine is an economical alternative to glucagon for hypotonic gastrointestinal radiography. PMID- 1612302 TI - Adjustable silicone gastric banding for obesity. AB - Adjustable gastric banding is the least invasive operation for morbid obesity. Forty-eight patients underwent surgical adjustable gastric banding between March 1990 and August 1991. In 15 of these patients, radiological examination was performed in the early postoperative period because of dysphagia and vomiting, revealing stenosis of the stoma in all cases (caliber less than 0.3 cm); in all patients we easily punched, with fluoroscopically guided observation, the inflatable portion and obtained a true calibration of the gastric banding. In seven patients radiological examination was performed 2 months after surgical treatment because of a lack of weight loss. Radiological findings explain surgical failure, revealing a too wide stoma in four patients, the absence of a gastric pouch due to a too high position of the band in two, and the caudal sliding of the banding in one patient. PMID- 1612301 TI - Prevalence of upper gastrointestinal disease in relation to age: radiologic and clinical implications. AB - Reports of 1126 endoscopies were reviewed to determine the age-related prevalence of upper gastrointestinal (UGI) diseases as a guide to radiologists performing UGI examinations. Results indicate that (1) there were positive findings in 78% of all endoscopic examinations, and thus most symptomatic patients can be expected to have at least one UGI abnormality; (2) many patients with UGI symptoms have two or more reportable disease processes; (3) the prevalence of serious or life-threatening disease, such as cancer or large ulcers, rises steadily with age; and (4) after age 60, approximately 60% of symptomatic patients have a serious UGI disease. Based on these findings, radiologists should not hesitate to make the diagnosis of multiple abnormalities and should expect to diagnose at least one abnormality in most symptomatic patients having an UGI study. Also, because of the high prevalence of serious lesions in the elderly, endoscopy should be considered for the initial examination of an elderly patient if poor physical status would render the radiologic examination difficult or unreliable. PMID- 1612303 TI - Gastric carcinoma after gastrojejunostomy for benign disease: radiographic findings. AB - Although it is not well recognized in the radiologic literature, gastric carcinoma has been reported to occur as a late complication of gastrojejunostomy for benign disease, even in the absence of partial gastrectomy. We present the radiographic findings in two patients with this complication and review clinical and experimental data supporting the role of gastrojejunostomy in the subsequent development of gastric carcinoma. PMID- 1612304 TI - Massive gastric distention due to duodenal involvement by retroperitoneal tumors. AB - We present three patients with retroperitoneal tumor involving the duodenum in whom upper gastrointestinal (GI) studies revealed delayed gastric emptying and massive gastric dilatation out of proportion to the degree of duodenal dilatation. While the radiographic findings mimicked acute gastric outlet obstruction, delayed films demonstrated narrowing and encasement of the duodenum at the site of obstruction in all three patients. Thus, the duodenum should be carefully evaluated radiographically in patients with acute gastric dilatation, particularly if there is a known history of malignancy. PMID- 1612305 TI - Duodenal intramural pseudodiverticulosis. AB - Although esophageal intramural pseudodiverticulosis is well described, similar pathology has not been demonstrated elsewhere in the gastrointestinal tract. Three cases are reported with identical changes in the duodenum, one of which had simultaneous esophageal involvement. All three patients were alcohol abusers. PMID- 1612306 TI - Intestinal leiomyomas: angiographic imaging. AB - A retrospective angiographic study was done on 19 patients with solitary leiomyomas of the small bowel, one patient with multiple leiomyomas, and two patients with leiomyosarcomas. All patients had gastrointestinal bleeding but no small bowel obstruction. Selective mesenteric angiography was the main diagnostic procedure. Tumoral hypervascularity and dense capillary staining within a well circumscribed mass were present in all patients. Prominent and irregular feeding arteries were seen in 19 cases and prominent draining veins in 20. Contrast extravasation indicating the site of active bleeding was shown in two patients. PMID- 1612308 TI - Sonographic findings in Richter's hernia. AB - Richter's hernia can present as a diagnostic challenge because of its usually small size and eccentric bowel wall involvement with limited luminal compromise. This article describes a case of Richter's hernia in the femoral canal and illustrates its sonographic features. PMID- 1612307 TI - Emergent embolotherapy of small intestine hemorrhage. AB - The efficacy of emergent embolotherapy was evaluated in six patients suffering hemorrhage from the small intestine. Hemorrhage was from the jejunum in four patients, from the ileum in one, and from Meckel's diverticulum in one. Superselective embolization of the arcade of the small intestine artery branch was performed in all patients with a coaxial catheter. Embolic materials used were Gelfoam particles alone or Gelfoam particles plus coils in earlier cases and microcoils in recent cases. Complete hemostasis was immediately achieved in all patients, but one patient died of disseminated intravascular coagulation. After stabilization of the patient's condition by hemostasis, elective surgery was performed on three patients suffering small intestine ulcer. Histopathologically, no bowel infarction was noted but mild mucosal inflammation with submucosal edema was found in the jejunum of two patients. We recommend embolization for life threatening small intestine hemorrhage, preferentially in situations where the blood vessel involved can be super-selectively occluded at the nearest level of the arcade of the vasa recta, lest the vasa recta should be occluded. PMID- 1612309 TI - Abdominal CT following liver transplantation. AB - Computed tomography (CT) is one of several imaging modalities employed in the evaluation of complications following orthotopic liver transplantation. Abdominal CT scans were performed in 92 (48%) of the first 190 liver transplant patients at our institution. These studies were retrospectively reviewed to determine the indications for CT in this population and to determine the incidences of the various CT findings. The major indication (70%) was detection of bile leakage, hemorrhage, or abscess. The role of CT was primarily to discover such abnormal fluid collections and guide their percutaneous drainage. This article describes a wide spectrum of common and uncommon findings following liver transplantation and illustrates their CT features. PMID- 1612310 TI - Peritoneal ovarian metastases simulating liver parenchymal metastases. AB - Ovarian carcinoma frequently metastasizes to the peritoneum, both locally in the pelvis and elsewhere. Computed tomography (CT) has a limited ability to identify peritoneal implants with a diameter of 2 cm or less. Three cases of subphrenic, diaphragmatic peritoneal implants, preoperatively at CT thought to represent liver parenchymal metastases, are presented. The difficulty in the differentiation of diaphragmatic peritoneal implants from metastases to the capsule and parenchyma of the liver is discussed. To achieve a radical liver resection in patients with ovarian carcinoma, metastatic peritoneal implants must be excluded during operation. PMID- 1612311 TI - In vivo analysis of gallstone composition by computed tomography. AB - In vivo computed tomography (CT) of the gallbladder was performed in 39 patients with known cholelithiasis and subsequently correlated with the chemical composition of the retrieved gallstones. Six CT patterns were identified: pattern 1, negative defect within the bile; pattern 2, nonvisualization of calculi; pattern 3, faint homogeneous central calcification; pattern 4A, thin rim of calcification; pattern 4B, thick rim of calcification; pattern 5, dense homogeneous central calcification. These CT patterns correlated well with cholesterol (p = 0.05) and calcium bilirubinate (p = 0.01) contents and CT attenuation values (p less than 0.001). The most common pattern was CT pattern 2 (56.5%). The authors conclude that there is good correlation of the CT pattern with gallstone composition. This simple approach can be used to help identify patients for therapy with chemical dissolution and/or lithotripsy. PMID- 1612312 TI - Role of oral cholecystography, real-time ultrasound, and CT in evaluation of gallstones and gallbladder function. AB - The capacity of oral cholecystography (OCG), real-time ultrasound (RUS), and computed tomography (CT) to detect gallstones and to analyze their size, number, and composition was tested preoperatively in 37 patients undergoing elective cholecystectomy. Gallbladder response to a standard meal was also evaluated by OCG and RUS. Gallstones were analyzed chemically for calcium, cholesterol, and bilirubin content. The results show that RUS is the most valuable test for detecting gallstones and is similar to OCG in measuring their size and number, whereas CT underestimates the stone size. Gallbladder function in terms of contractibility can be evaluated by RUS and OCG, but RUS provides useful information even if the gallbladder is not opacified at OCG. CT is more accurate than OCG in detecting the presence of calcium, and CT attenuation numbers are positively correlated with calcium content of the stone (r = 0.87, p less than 0.01). PMID- 1612313 TI - Splenic abscess: sonographic diagnosis and percutaneous drainage or aspiration. AB - During a recent 5-year period, 12 patients with splenic abscesses were evaluated by abdominal ultrasound (US) examination. Multifocal abscesses were noted in seven patients, three of them were secondary to infectious endocarditis, three were in immunosuppressed state, and one was caused by tuberculosis. The latter four patients had developed splenic microabscesses with a diameter of less than 1.5 cm. The larger abscesses showed an irregular wall, weak or no internal echoes, ovoid or round in shape, and accompanied by mild to moderate distal acoustic enhancement. Wedge-shaped abscesses were typically noted in patients with infectious endocarditis and septic embolism. US-guided percutaneous drainage was done in five patients (abscesses greater than 4 cm). Simple aspiration in conjunction with antibiotic administration was done for seven smaller abscesses (diameter less than 3.5 cm) in five patients. A second drainage, either for a dislodged catheter or a recurrent abscess, was performed in two cases. All patients had uneventful clinical course following this therapeutic approach. PMID- 1612314 TI - Comparison of precontrast, postcontrast, and delayed CT scanning for the staging of rectal carcinoma. AB - An attempt is made to establish the most appropriate examination procedure for staging rectal carcinoma by computed tomography (CT). Twenty-two patients with rectal carcinoma had CT performed preoperatively. The following three CT sequences were performed in all patients: a precontrast scan with 10-mm slices; a rapid sequence scan with 5-mm slices during bolus injection of contrast medium; and a postcontrast scan after a 10-min delay. Tumor extension and the presence of perirectal lymph nodes were evaluated separately and independently in all three CT sequences according to the TNM classification. All patients had surgical follow-up and the CT scans were compared to the surgical and histopathological findings. There was no significant difference in diagnostic outcome in the three CT procedures. Information obtained by frontal and lateral scout views were compared, and the lateral scout view proved more informative than the frontal scout view. For staging rectal carcinoma, narrow slice scanning and intravenous contrast media are superfluous and should be reserved for special cases. We recommend the use of lateral scout views. PMID- 1612315 TI - Silent rectal perforation after endoscopic polypectomy: CT features. AB - A case of silent extraperitoneal rectal perforation secondary to colonoscopic polypectomy is presented. Computed tomography (CT) demonstrated pathways of gas diffusion from the perirectal site to different compartments of the retroperitoneum, to the mediastinum and peritoneum. PMID- 1612316 TI - Actinomycosis of the distal colon and rectum. AB - Actinomycosis of the colon has rarely been reported; two such cases are presented. A predisposing factor appears to be the presence of a pre-existing intrauterine device (IUD). This history was present in one case in which there was perisigmoid abscess, local extension, and fistulous tract or the anterior abdominal wall. A second patient had anorectal involvement which resembled Crohn's disease, and was found to be HIV positive. There was mucosal irregularity, wall thickening, reactive adenopathy, perirectal fascial thickening, and a sinus tract, which responded well to penicillin. It is unclear if there is an increased incidence of clinical actinomycosis in the HIV positive population, as it has not to our knowledge been previously reported. PMID- 1612317 TI - The relationship between size and number of common bile duct stones. PMID- 1612318 TI - Dynamic anal manometry: physiological variations and pathophysiological findings in fecal incontinence. AB - A recently developed technique for dynamic anal manometry was used to study 40 healthy volunteers and 23 patients with fecal incontinence. Seven parameters of anal function were measured. Intraindividual variation of the parameters was studied in 5 females and 5 males. The results of dynamic anal manometry were compared with standard pull-through static anal manometry and correlated well. During opening of the anal sphincter at rest, compliance increased with increasing distension. Males had higher maximal closing pressures during squeeze and lower anal compliance during squeeze than females. There was no sex differences of the sphincter measurements at rest. Age had little effect, and gender had no effect on the measurements. With standard anal manometry, 6 of 23 patients with fecal incontinence both had maximal resting pressure and maximal squeeze pressure within the normal range. When dynamic anal manometry was used, all 23 patients showed one or more abnormal values. The method of dynamic anal manometry provides an opportunity for a more thorough assessment of anal sphincter function than previous manometric methods. PMID- 1612319 TI - Intravenous erythromycin overcomes small intestinal feedback on antral, pyloric, and duodenal motility. AB - The retardation of gastric emptying caused by intraduodenal lipid is associated with suppression of antral contractions and stimulation of localized pyloric contractions. Similar patterns of motility have been described in patients with gastroparesis. The effect of erythromycin on the antropyloroduodenal motor responses to intraduodenal lipid was investigated. In 17 volunteers an intraduodenal lipid infusion (10% Intralipid) was given at 1 mL/min for 50 minutes. Either erythromycin (3 mg/kg) or saline was administered IV for 15 minutes, beginning 20 minutes after the start of the intraduodenal lipid infusion. Antral, pyloric, and duodenal motility were measured with a sleeve/sidehole manometric assembly. Intraduodenal lipid stimulated localized pyloric contractions. Erythromycin suppressed localized phasic (P less than 0.003) and tonic (P less than 0.002) pyloric pressure waves and stimulated antral (P less than 0.003) and duodenal pressure waves (P less than 0.02). After erythromycin antral pressure waves were usually of high amplitude (greater than 50 mm Hg) and often associated with duodenal pressure waves. It was concluded that erythromycin overcomes the effects of intraduodenal lipid on antral, pyloric, and duodenal motility. These effects probably contribute to the gastrokinetic properties of erythromycin. PMID- 1612320 TI - Abnormal REM sleep in the irritable bowel syndrome. AB - Motor abnormalities of the small bowel that occur only during the waking state have been reported in the irritable bowel syndrome (IBS), suggesting that central nervous system arousal is a necessary condition for expression of the disorder and that it may reflect inappropriate brain-gut interaction. This possible relationship was explored further by synchronous polysomnography and recording of upper small bowel motility in six healthy subjects and six patients with IBS. During sleep, there was no difference in the patterns of intestinal motility between the two groups. There was no difference between the rapid eye movement (REM) latency or number of REM episodes, but the proportion of REM sleep was markedly increased (36.5% +/- 5.7% vs. 18.2% +/- 5.7%; P less than 0.01) in the IBS group, although the duration of sleep was similar (468 +/- 13 minutes in IBS vs. 444 +/- 10 minutes in controls; P greater than 0.1). Sleep apnea was detected in three of six patients with IBS but was not seen in controls. The data are consistent with the model of IBS as a disorder of brain-gut interaction. PMID- 1612321 TI - Modulation of chloride secretion in the rat colon by intracellular bicarbonate. AB - Extracellular HCO3- stimulates colonic net Cl- absorption in part by inhibiting basal Cl- secretion. This inhibition was investigated by measuring serosal-to mucosal Cl- flux across short-circuited colonic segments from Sprague-Dawley rats. Mucosal intracellular pH and bicarbonate were estimated using the pH sensitive dye BCECF. When extracellular [HCO3-] ([HCO3-]e) was increased from 0 to 39 mmol/L at PCO2 33 mm Hg, mucosal intracellular [HCO3-] ([HCO3-]i) increased to 25.3 mmol/L and serosal-to-mucosal Cl- flux decreased from 13.0 to 7.1 microEq.cm-2.h-1. When PCO2 was increased to 72 mm Hg at [HCO3-]e 39 mmol/L, [HCO3-]i increased to 29.8 mmol/L and serosal-to-mucosal Cl- flux decreased to 5.9 microEq.cm-2.h-1. In Ringer's solution containing 21 mmol/L HCO3- and 20 mmol/L Cl- (but not 100 mmol/L Cl-), increasing PCO2 from 21 to 70 mm Hg increased [HCO3-]i to 22.6 mmol/L and decreased serosal-to-mucosal Cl- flux from 3.0 to 1.7 microEq.cm-2.h-1. Overall, serosal-to-mucosal Cl- flux was inversely related to [HCO3-]i on either side of an [HCO3-]i plateau of 9-18 mmol/L at which flux was stable. These data suggest that [HCO3-]i is an important modulator of basal Cl- secretion in rat distal colon. PMID- 1612322 TI - Pharyngeal clearance during swallowing: a combined manometric and videofluoroscopic study. AB - The deglutitive pharyngeal contraction was analyzed using simultaneous videofluoroscopic and manometric studies of eight volunteers. Anterior, posterior, and longitudinal movements of the pharyngeal surfaces, relative to the cervical vertebrae, were measured during swallows of 5 and 10 mL of liquid barium. Profound pharyngeal shortening during bolus transit through the pharynx eliminated access to the larynx and elevated the upper esophageal sphincter to within 1.5 cm of the retrolingual pharynx. Bolus head movement through the pharynx preceded the propagated pharyngeal contraction and registered manometrically as a slight intrabolus pressure before the major pressure complex. Contraction in the horizontal plane began after bolus head transit and culminated with stripping of the bolus tail through the pharynx. Prolonged upper sphincter opening with the larger-volume swallows resulted from a delayed onset rather than altered propagation of the horizontal pharyngeal contraction. It is concluded that the propagated pharyngeal contraction facilitates pharyngeal clearance but has a minimal role in the process of bolus propulsion during swallowing. The propagated contraction works in concert with profound pharyngeal shortening to minimize hypopharyngeal residue after a swallow. PMID- 1612323 TI - Deposition of eosinophil granule major basic protein in eosinophilic gastroenteritis and celiac disease. AB - Degrees of eosinophil infiltration and eosinophil degranulation, as evidenced by localization of the eosinophil granule major basic protein (MBP), were compared in patients with eosinophilic gastroenteritis, patients with celiac disease, and healthy controls using a specific indirect immunofluorescence technique for the localization of MBP. Formalin-fixed, paraffin-embedded biopsy specimens from the mucosa of the stomach and small intestine of 11 patients with eosinophilic gastroenteritis, from the small intestine of 4 patients with celiac disease, and from the stomach and/or upper small intestine of 18 healthy asymptomatic volunteers were tested. Degrees of eosinophil infiltration and extracellular deposition of MBP were graded by two blinded observers; each section was given a score from 0 (nil) to 4 (marked). In the small bowel biopsy specimens, both eosinophil infiltration and extracellular MBP deposition scores were significantly greater in patients with eosinophilic gastroenteritis and in patients with celiac disease than in controls. In the gastric biopsy specimens, extracellular MBP deposition scores were significantly increased in patients with eosinophilic gastroenteritis compared with controls even though eosinophil infiltration scores did not differ significantly at this site. The results support the hypothesis that the eosinophil, through toxic cationic proteins such as MBP, plays a role in the pathogenesis of these diseases. PMID- 1612324 TI - Pericrypt eosinophilic enterocolitis and chronic diarrhea. AB - An unusual pattern of eosinophilic infiltration around intestinal crypts was detected in mucosal biopsy specimens of 10 patients with chronic diarrhea, half of whom had evidence of systemic connective tissue disease. The median duration of symptoms was 11 months, and no other explanation for diarrhea could be determined in any case. The cellular infiltrate on biopsy specimens was present deep in the mucosa of small and large intestinal specimens, separating crypt bases from the muscularis mucosae and penetrating the latter. Consistent with the microscopic findings, surface mucosal appearance by endoscopy was uniformly normal. These histological features of colonic biopsy specimens were statistically differentiated from those of asymptomatic subjects (n = 8), subjects with diarrhea-predominant irritable bowel syndrome (n = 6), and subjects with collagenous colitis (n = 7) or lymphocytic colitis (n = 5). Diarrhea improved in five of seven subjects treated with oral prednisone or prednisone in conjunction with azathioprine (median follow-up period, 2.2 years). Histological changes on subsequent biopsy specimens correlated closely with symptomatic status. These findings strongly suggest that chronic diarrhea is related to this pericrypt eosinophilic enterocolitis, a pathological lesion often associated with features of systemic connective tissue disease. The disorder appears responsive to corticosteroid therapy in some cases. PMID- 1612325 TI - Excessive production of reactive oxygen metabolites by inflamed colon: analysis by chemiluminescence probe. AB - Reactive oxygen metabolites (ROMs) are involved in inflammatory diseases and are postulated to contribute to tissue injury in colitis. To determine whether excessive ROMs are generated by inflamed colonic mucosa and to identify possible sources and type of ROMs, mucosal ROMs were estimated in rats and humans using a chemiluminescence probe. Colitis was induced in rats by intracolonic injection of acetic acid or intraperitoneal injection of mitomycin C. Intact, inflamed colon in rats produced more ultraweak chemiluminescence than normal colon. Inflamed mucosal scrapings from both rat models produced significantly more luminol enhanced chemiluminescence. Addition of catalase, an H2O2 scavenger, or azide, a myeloperoxidase inhibitor, into the media significantly decreased chemiluminescence from inflamed mucosal scrapings. Indomethacin, an antioxidant cyclo-oxygenase inhibitor, also decreased chemiluminescence, but MK-866, a 5 lipoxygenase inhibitor, had no effect. Colonic biopsy specimens obtained during colonoscopy from patients with ulcerative colitis also produced more catalase inhibitable chemiluminescence than normal colonic mucosa. These data indicate that excessive ROMs are produced by inflamed colonic mucosa in both humans and rats, which may contribute to tissue injury. PMID- 1612326 TI - Role of nitric oxide in esophageal peristalsis in the opossum. AB - To explore the involvement of NO in normal peristalsis, the effects of inhibitors of NO synthase, including N omega-nitro-L-arginine (L-NNA) and N omega-nitro-L arginine methyl ester (L-NAME), on esophageal peristaltic contractions induced by diverse stimuli that may involve different neuronal circuits were studied. Studies were performed in opossums. Experimental conditions in vivo included primary peristalsis (P) induced by pharyngeal stroking, short-train (1 second) electrical stimulation of the vagus nerve which caused peristaltic (S) contractions, and long-train (10 second) electrical stimulation of the vagus nerves which caused contractions at the onset of (A contractions) and after (B contractions) the stimulation period. In vitro experiments were performed on strips of esophageal circular muscle using electrical field stimulation which caused contractions at the onset of (on contractions) and after (off contractions) the stimulation period. The administration of L-NAME significantly decreased the latency period and reduced the latency gradient for P contractions, thereby increasing the velocity of peristalsis. Concomitant administration of atropine prolonged the latency period but did not restore the latency gradient. L NAME abolished B contractions in a dose-dependent fashion. In vitro, L-NAME caused dose-dependent inhibition of off contractions and augmentation of on contractions. These studies support the hypothesis that NO may be involved in (a) both the latency period and the latency gradient, as well as in the contraction amplitude of esophageal peristalsis; and (b) esophageal B and off contractions. PMID- 1612327 TI - Acute necrotizing pancreatitis in the opossum: earliest morphological changes involve acinar cells. AB - Acute pancreatitis was induced by ligating the opossum common biliopancreatic duct immediately proximal to its entry into the duodenum, and macroscopic as well as microscopic changes were evaluated during the subsequent 24 hours. Transient pancreatic edema and progressive hyperamylasemia were noted within 6 hours of pancreatic and bile duct ligation. Light microscopic evidence of pancreatic injury including acinar cell necrosis, hemorrhage, fat necrosis, and inflammatory cell infiltration was noted within 12 hours of duct obstruction. Electron microscopic changes included massive dilatation of the rough endoplasmic reticulum and disruption of the apical plasmalemma of acinar cells during the initial 3 hours. These observations indicate that pancreatic and bile duct ligation in the opossum results in the rapid (less than 24 hours) appearance of changes consistent with acute hemorrhagic and necrotizing pancreatitis and that the initial lesion in this model of experimental pancreatitis involves acinar cells. PMID- 1612328 TI - Changes in gallbladder bile composition following gallstone formation and weight reduction. AB - Changes in gallbladder bile composition that occurred in patients who developed gallstones during weight reduction were evaluated. Bile was sampled directly from the gallbladder in 11 morbidly obese patients with no gallstones at the time of gastric bypass surgery and after gallstones had formed at cholecystectomy. Bile salt concentration ([BS]) increased significantly from a mean of 82.7-157.7 mmol/L (P less than 0.05). The concentration of cholesterol in gallbladder bile increased slightly and cholesterol saturation declined slightly with weight reduction and gallstone formation. Gallbladder mucin concentration increased 18 fold from a mean of 62 to 1110 micrograms/mL (P less than 0.001). Both free [Ca2+] and total calcium [Ca] increased 40% from mean values of 1.12 and 5.05 mmol/L at gastric bypass to 1.86 and 8.60 mmol/L after gallstone formation (P less than 0.05). The increase in [Ca2+] observed after gallstone formation was much greater than anticipated from changes in [BS] alone. This excess [Ca2+] in gallbladder bile increased curvilinearly with increasing mucin concentration. These results show that both gallbladder mucin and [Ca2+] increase with gallstone formation in humans and that mucin may modulate [Ca2+] in gallbladder bile. PMID- 1612329 TI - Portal-systemic shunting and the disruption of circadian locomotor activity in the rat. AB - To determine if the extent of portal-systemic shunting (PSS) influences the disruption of circadian function in chronic liver disease, locomotor activity was examined in two rat models with varying degrees of PSS, i.e., portal vein ligation (PVL) and end-to-side portacaval anastomosis (PCA). Animals were housed in individual activity cages under conditions of 12 hour light/12 hour darkness (weeks 0-3), then under conditions of constant dim light (weeks 4-7). Cages were equipped with running wheels connected to a continuous recorder, and daily tracings of running activity were recorded for 7 weeks. Computer analysis of wheel revolutions per hour with a chi 2 periodogram was used to calculate Qp, a measure of the amplitude of a circadian rhythm. The degree of PSS was measured by means of radioactive microspheres injected into the ileocolic vein and spleen. PVL rats were found to have PSS from the splenic and mesenteric territories of 88% and 27%, respectively; circadian periodicity was maintained in all PVL rats. PCA rats had complete shunting (greater than 99%) and showed a range of disrupted circadian rhythms from blunting of the amplitude to complete absence of the locomotor activity rhythm. This spectrum of disorganization occurred in spite of similar degrees of liver atrophy and weight gain. Whereas PCA in rats markedly disturbs the circadian rhythm of locomotor activity, animals with considerably less PSS from PVL exhibit normal behavior. The extent of PSS could be a variable affecting the expression of circadian rhythms in liver disease. PMID- 1612330 TI - Hemodynamic evaluation of octreotide in patients with hepatitis B-related cirrhosis. AB - The hemodynamic effects of octreotide were studied in 20 patients with hepatitis B-related cirrhosis. In patients receiving a 100-micrograms bolus and a 100 micrograms/h infusion, heart rate, cardiac index, and systemic vascular resistance showed no significant changes, whereas right atrial pressure, pulmonary capillary wedge pressure, and inferior vena cava pressure decreased significantly after octreotide infusion compared with basal values. In contrast, in patients receiving a 50-micrograms bolus and a 50-micrograms/h infusion, all the systemic hemodynamic values were unaffected. In both groups of patients receiving two different doses of octreotide, the estimated hepatic blood flow, hepatic indocyanine green clearance, and wedge hepatic venous pressure were significantly reduced at 60 minutes after octreotide administration compared with basal values, whereas the hepatic venous pressure gradient remained unchanged. It is concluded that the two different doses of octreotide administration result in the reduction of the wedge hepatic venous pressure and the hepatic blood flow of a similar magnitude, whereas the hepatic venous pressure gradient is unaffected. Octreotide induces discrepant systemic hemodynamic response; this effect is dose related. PMID- 1612331 TI - Nitric oxide mediates hyporeactivity to vasopressors in mesenteric vessels of portal hypertensive rats. AB - Increased levels of circulating vasodilators have been claimed to be the causative factor in the hyporesponsiveness to endogenous vasopressors in portal hypertension. To investigate whether this hyporeactivity to vasopressors is also present in an in vitro system perfused with a synthetic medium, the responsiveness to graded concentrations of norepinephrine, arginine-vasopressin, and potassium chloride was tested in perfused superior mesenteric arterial beds of normal rats and rats with portal hypertension induced by partial portal vein ligation (PVL). The same vasopressors were tested after incubation of vessel preparations with the stereo-specific nitric oxide formation inhibitor N omega nitro-L-arginine (NNA, 10(-4) mol/L). Vessel preparations of PVL compared with normal rats (n = 8 per group and vasopressor) expressed a significant (P less than 0.05) hyporeactivity to norepinephrine, arginine-vasopressin, and potassium chloride over a wide range of concentrations. This hyporesponsiveness was overcome by preincubating vessel preparations with NNA. In summary, portal hypertension is accompanied by a significant in vitro hyporeactivity of splanchnic vessels to norepinephrine, arginine-vasopressin, and potassium chloride, and secretion of nitric oxide in this preparation seems responsible for this blunted response. PMID- 1612332 TI - A novel exocrine protein associated with pancreas transplantation in humans. AB - After pancreas transplantation, signs of acute pancreatitis are found in the grafted tissue. Pancreatic juice secreted from this organ was analyzed by gel electrophoresis. Initially, the pattern of secretory proteins was similar to that of the juice collected from normal individuals, but high levels of albumin were present. Within 2 days after reperfusion of the grafted pancreas, proteins of molecular weights 17,000-20,000 increased remarkably. Separation by two dimensional gel electrophoresis showed that this was largely due to the appearance of new a protein, present neither in the juice collected immediately after reperfusion nor in normal pancreatic juice. After transfer onto nitrocellulose, this additional protein was detected by antibodies directed against the recently described rat "pancreatitis-associated protein." Maximal amounts of approximately 7.5% of total secretory protein were found 5 days after transplantation. The concentration of the protein decreased in the further course but was still detectable after 45 days. The isoelectric point (7.1) and the molecular weight (17,500) were similar to those of the rat protein. It is concluded that after inflammation induced by pancreatic transplantation, the human pancreas secretes high amounts of a protein not present in normal juice. Because of its similarities to the rat pancreatitis-associated protein it is designated human pancreatitis-associated protein. PMID- 1612333 TI - Serum levels of cytokines in chronic liver diseases. AB - Serum levels of interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), and C-reactive protein (CRP) were investigated in patients with chronic liver diseases (CLD) and correlated with the type of underlying disease and various clinical and laboratory parameters. Two hundred sixty-four patients suffering from various CLD were studied; 136 cases presented with liver cirrhosis, and 128 patients were in the noncirrhotic stage of their underlying liver diseases. Serum levels of IL-1 beta, IL-6, TNF-alpha, IFN-gamma, and CRP were elevated in patients with CLD. Endogenous cytokine patterns in CLD were stage dependent and only marginally affected by the type of underlying disease. The cirrhotic group of CLD patients showed higher serum levels in IL-1 beta, IL-6, TNF-alpha, and CRP than did noncirrhotic cases, and these differences reached the level of statistical significance. IL-1 beta and TNF-alpha values were closely correlated but did not correlate with IL-6 levels. Elevated concentrations of cytokines represent a characteristic feature of CLD regardless of underlying disease. This and the apparent stage-dependency suggest that enhanced endogenous cytokine levels represent a consequence of liver dysfunction rather than of inflammatory disease. PMID- 1612334 TI - Hemodynamic effects of endotoxin and platelet activating factor in cirrhotic rats. AB - Acute infections may influence the hemodynamic alterations of liver disease. Therefore, the hemodynamic effects of endotoxin (LPS E. coli 0111:B4) in conscious, normal, and cirrhotic rats were compared. Endotoxin decreased cardiac index in cirrhotic but not in normal rats. Although the effect of endotoxin on portal tributary blood flow was minor in all animals, a reduction in portal pressure was found in cirrhotic rats. Because the most marked hemodynamic effects were observed in cirrhotic rats, the second part of our study investigated whether platelet activating factor played a role in endotoxin-induced hemodynamic alterations in the cirrhotic model. Platelet activating factor reduced cardiac index and kidney blood flow but did not influence portal tributary blood flow. Two antagonists to platelet activating factor reduced the adverse renal blood flow lowering effects of endotoxin in cirrhotic rats. Thus, it is suggested that the hemodynamic changes observed in cirrhosis may be aggravated during acute infections. Under this condition, antagonists to platelet activating factor may be of benefit in the prevention of hemodynamic complications induced by endotoxin. PMID- 1612335 TI - Liver triglyceride concentration and body protein metabolism in ethanol-treated rats: effect of energy and nutrient supplementation. AB - The objective of this study was to compare the metabolic effects of long-term ethanol consumption with oral (Lieber-DeCarli) and enteral feeding techniques. Enteral feeding allowed administration of greater amounts of energy and nutrients. After 21 days of treatment using the Lieber-DeCarli technique, the ethanol-treated rats had the following significant (P less than 0.05) differences from pair-fed controls: lower cumulative nitrogen balance (days 5-21; 2.8 +/- 0.1 g N vs. 3.5 +/- 0.1 g N), lower protein content of gastrocnemius muscle (289 +/- 17 mg vs. 358 +/- 11 mg) and intestinal mucosa (461 +/- 19 mg vs. 577 +/- 40 mg), higher plasma leucine concentration (147 +/- 8 mumol/L vs. 102 +/- 8 mumol/L), higher liver protein content (2222 +/- 122 mg vs. 1679 +/- 58 mg), and higher liver triglyceride concentration (38.4 +/- 2.8 mg/g vs. 8.7 +/- 1.0 mg/g). When rats received the same amount of nitrogen (1.5 g.kg-1.day-1) and ethanol (13 g.kg 1.day-1) but 16.3% more energy and nutrients by a surgically implanted gastric cannula (enterally fed), the effects of ethanol on nitrogen balance, tissue protein content, plasma leucine concentration, and liver triglyceride concentration were similar to those observed in the rats fed orally. It is concluded that the metabolic effects observed using the Lieber-DeCarli feeding technique are due to ethanol per se and not the synergism of ethanol and undernutrition as recently suggested. PMID- 1612336 TI - The influence of bile salts on small intestinal motility in the guinea pig in vitro. AB - The effect of bile salts on intestinal motility is unclear. In the current study, isometric contractions of the guinea pig terminal ileum were examined in vitro. Dose-response curves to known agonists cholecystokinin (CCK), bethanechol, and KCl were constructed alone and in the presence of atropine (10(-6) mol/L), tetrodotoxin (10(-6) mol/L), and different bile salts, namely, taurodeoxycholate, tauroursodeoxycholate, taurocholate, glycodeoxycholate, and glycoursodeoxycholate. These bile salts, at levels as low as 5 and 50 mumol/L, significantly depressed (P less than 0.05) CCK-induced contractions throughout the dose-response curves and were concentration dependent. This depressant effect was not dependent on the bile salt species or any apparent physicochemical differences between them. The inhibitory effect was also specific for certain agonists such as CCK (the action of which was partially mediated by cholinergic nerves, being depressed by atropine and abolished by tetrodotoxin), field stimulation, and nicotine. Bile salts had no effect on either bethanechol- or KCl induced contractions. Such bile salt inhibition of excitatory, cholinergic, enteric neurons may slow transit through the ileum, enhancing the time for absorption and conserving the bile salt pool. PMID- 1612337 TI - Expression of the polymeric immunoglobulin receptor by cultured aged rat hepatocytes. AB - The Fischer rat shows an age-related loss of both hepatic blood to bile transport and secretory component-specific binding sites for polymeric immunoglobulin (Ig) A. This age-related loss of hepatic IgA receptor function is also shown by cultured hepatocytes. It is reported here that compared with young cells, binding and uptake of 125I-polymeric IgA by cultured hepatocytes was markedly reduced in cells from senescent animals. In addition, cells from old animals showed markedly diminished secretion of secretory component determined by enzyme-linked immunosorbent assay and expression of polymeric immunoglobulin receptor determined by incorporation of 35S-labeled amino acid and fluorography. It is suggested that the age-related decrease in IgA receptor-mediated transport from serum to bile results, at least in part, from decreased expression and secretion of total hepatic secretory component. PMID- 1612338 TI - Visual event-related P300 potentials in early portosystemic encephalopathy. AB - Visual event-related P300 potentials, conventional visual evoked potentials, and psychometric tests were applied to patients with noncirrhotic chronic liver disease and to clinically nonencephalopathic and encephalopathic cirrhotics to compare their diagnostic efficacy in detecting early portosystemic encephalopathy (PSE). Sixty-four investigations were performed in 58 patients. The latencies of the P300 parameters were significantly longer in both the encephalopathic and nonencephalopathic cirrhotics than in the noncirrhotics, indicating distinctly abnormal cortical processing of visual stimuli in cirrhotic patients. The visual P300 potentials showed the highest sensitivity and specificity for grade I PSE. Abnormal P300 test results were also found in 78% of the clinically nonencephalopathic cirrhotics, while psychometric tests showed abnormalities in only 41%. The P300 latencies were similar in alcoholic and nonalcoholic cirrhotics. Significant inverse correlations were found between the P300 latencies and measures of quantitative liver function such as galactose elimination capacity and aminopyrine breath test. It is concluded that visual event-related P300 potentials are a sensitive index of subclinical and grade I PSE. Furthermore, the degree of cognitive dysfunction detected by this method in patients with liver cirrhosis appears to be related to the reduction in hepatic metabolic capacity. PMID- 1612339 TI - Extracorporeal shock-wave lithotripsy and ursodiol versus ursodiol alone in the treatment of gallstones. AB - The efficacy and occurrence of adverse effects after two forms of treatment were compared in 111 patients with biliary colic and radiolucent gallstones in this prospective, nonrandomized study. Fifty-four patients received extracorporeal shock-wave lithotripsy (ESL) plus ursodiol, and 57 patients received ursodiol alone. Among patients with a single stone (5-20 mm in size), no patient treated with ursodiol alone had a stone-free gallbladder at 6 or 12 months after treatment; of those treated with ESL plus ursodiol, 15 of 24 patients (63%) had a stone-free gallbladder at 6 months and 17 of 20 patients (85%) at 12 months. For patients with multiple stones (with an aggregate diameter of less than or equal to 30 mm), the incidence of a stone-free gallbladder was 2 of 43 patients (5%) at 6 months and 8 of 35 patients (23%) at 12 months in the ursodiol treatment group. In the ESL plus ursodiol group, the incidence of a stone-free gallbladder was 7 of 22 patients (32%) at 6 months and 9 of 20 patients (45%) at 12 months. Two patients in the ESL plus ursodiol group (4%) and 13 patients in the ursodiol group (24%) underwent cholecystectomy. Both patients in the ESL plus ursodiol therapy and 4 patients in the ursodiol group had emergency cholecystectomies because of acute cholecystitis. The remaining 9 patients in the ursodiol group had elective cholecystectomies. In this nonrandomized, prospective study, ESL plus ursodiol treatment produced stone-free gallbladders at a faster rate than ursodiol alone in patients with either single or multiple gallstones. PMID- 1612340 TI - Incidence, prevalence, and clinical course of hepatitis C following liver transplantation. AB - Hepatitis C virus (HCV) is the agent responsible for posttransfusion hepatitis. The incidence, timing, and clinical course of HCV positive hepatitis in liver transplant recipients are unknown. Three hundred and seventeen donor-recipient liver transplant pairs were grouped on the basis of their pretransplant HCV antibody status. The biopsy findings were examined. Four distinct groups were identified on the basis of HCV serology: group I, both were negative; group II, donor was negative and recipient was positive; group III, donor was positive and recipient was negative; group IV, both were positive. The prevalence of anti-HCV positivity in recipients was 13.6%. The rate of seroconversion was 9.2%. Histologic hepatitis not ascribable to any specific cause other than non-A, non-B (NANB) hepatitis occurred in 13.8%. The incidence of histologic chronic active hepatitis was 1.6%, and none progressed to cirrhosis. The concordance rate for a positive anti-HCV serology and NANB hepatitis was 2.8%. Of the 35 patients (group II and IV) with positive anti-HCV serology pretransplant, only 17 were positive posttransplantation. Based on these data it can be concluded that posttransplant NANB hepatitis occurred in 13.8% of liver recipients. Twenty percent of these were anti-HCV positive. Progression to histologic chronic active hepatitis occurs over a period of 1-5 years in 1.6% of cases. PMID- 1612341 TI - Paraneoplastic hepatopathy associated with soft tissue sarcoma. AB - Paraneoplastic syndromes associated with mesodermal tumors are relatively uncommon. An unusual case manifested by fever, anemia, thrombocytosis, coagulopathy, and idiopathic cholestatic liver dysfunction in association with soft tissue sarcoma is reported. A paraneoplastic syndrome is postulated in the absence of anatomic obstruction of bile flow, evidence of an infectious etiology, or neoplastic hepatic involvement. PMID- 1612342 TI - Nonspecific esophageal motor disorder associated with thickened muscularis propria of the esophagus. AB - A case of a nonspecific esophageal motor disorder associated with muscular hypertrophy, revealed by endoscopic ultrasonography, is reported. A 41-year-old man was admitted to the hospital with chest pain and dysphagia. Manometric studies of the esophagus disclosed prolonged duration of propulsive waves with normal amplitude. Endoscopic ultrasonography showed downward thickening of the esophageal muscular layer; the maximum thickness was found at the lower esophageal sphincter. Thickening of the esophageal wall of unknown etiology has been reported as a diffuse esophageal muscular hypertrophy. Previous cases of diffuse esophageal muscular hypertrophy were diagnosed by autopsy. Some cases involved dysphagia and/or chest pain. Therefore, some of the reported cases of nonspecific esophageal motor disorders may have been associated with diffuse esophageal muscular hypertrophy. Association of the two categories was shown by endoscopic ultrasonography for the first time in the present case. Endoscopic ultrasonography is a useful tool for the diagnosis of the thickening of the muscular layer of the esophagus. PMID- 1612343 TI - Colonic short-chain fatty acids: fuel from the lumen? PMID- 1612344 TI - Helicobacter pylori and non-ulcer dyspepsia. PMID- 1612345 TI - Interleukin 8, neutrophils, and acute inflammation. PMID- 1612346 TI - New treatment for primary sclerosing cholangitis: promising results with ursodiol. PMID- 1612347 TI - Lower esophageal sphincter: how to quantitate? PMID- 1612348 TI - N-acetylcysteine is useless for oral gallstone dissolution. PMID- 1612349 TI - Effect of age and sex on hepatic intraacinar enzyme profile. PMID- 1612350 TI - Hepatotoxicity associated with piroxicam use. PMID- 1612351 TI - Surgical abdomen due to Clostridium difficile-induced colitis. PMID- 1612352 TI - Enteric protein losing in sarcoidosis revisited. PMID- 1612353 TI - Cholecystokinin exerts a tonic inhibitory influence on gastric acid secretion and gastrin release. PMID- 1612354 TI - Nutritional therapy for alcoholic hepatitis. VA Cooperative 275 Study Group. PMID- 1612355 TI - Towards a relatively inexpensive, noninvasive, accurate test for colonic motility disorders. AB - Currently available clinical tests of colonic transit, such as the radiopaque marker method, are useful to detect delayed transit but may be less sensitive for rapid transit. The aim of this study was to develop a relatively inexpensive, noninvasive, accurate test of colonic transit using selected scintigraphic observations within the first 24 hours after ingestion of a pH-sensitive, methacrylate-coated, delayed-release capsule containing 111In-labeled resin pellets. The authors' previously published colonic transit data on 22 healthy subjects, 9 patients with diarrhea-predominant irritable bowel syndrome, and 7 patients with idiopathic constipation and previously unpublished data on 4 patients with carcinoid diarrhea were analyzed. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected combinations or simple summaries of transit. Among combined transit summaries, the emptying rate of the proximal colon was significantly different between healthy and constipation groups; the geometric center of isotope in the colon at 4 hours was significantly greater in the diarrhea group than in healthy controls; the geometric center at 24 hours was significantly lower in the constipation group than in the other two groups. From the logistic discriminant analysis, simple summaries of transit also had significant discriminant value; these included the isotopic contents in the ascending, transverse, and descending colon at 4 hours and the counts in the ascending and transverse colon and stool at 24 hours. At 90% sensitivity, the specificity of the transverse colon counts at 4 hours was 79%, which is identical to the specificity of the proximal colon emptying rate, both adjusted for age. Thus, quantitation of isotopic counts in colonic regions on scans taken at 4 and 24 hours provides an accurate summary of colonic transit, with acceptable specificity at a high sensitivity in the detection of motility disorders of the colon. PMID- 1612356 TI - Nitric oxide pathway in rectoanal inhibitory reflex of opossum internal anal sphincter. AB - The role of nitric oxide in relaxation of the internal anal sphincter (IAS) in response to the rectoanal reflex was studied in the opossum. Resting pressures in the IAS (IASP) were monitored using low-compliance continuously perfused catheters. The NO-synthase inhibitor L-NG-nitro-arginine (L-NNA) caused significant and dose-dependent suppression of the decrease in IASP in response to the reflex mimicked by the rectal balloon distention. NO-synthase inhibitor blocked IAS relaxation in response not only to rectoanal reflex but also to other neural stimuli such as sacral nerve stimulation, local intramural stimulation, and the nicotinic ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium. Suppression of the neurally mediated IAS relaxation by L-NNA was stereoselective; D-NNA had no effect on the relaxation. The suppression of the rectoanal reflex induced IAS relaxation by L-NNA was completely reversed by NO precursor L arginine stereoselectively as D-arginine failed to reverse the suppressed IAS relaxation. Sodium nitroprusside caused a decrease in IASP that was modified neither by the neurotoxin tetrodotoxin nor by L-NNA. Furthermore, the decrease in IASP by the direct-acting beta-adrenoceptor agonist isoproterenol was also not modified by the inhibitor of NO synthase. It is concluded that NO or an NO-like substance is an important mediator of IAS relaxation in response to noradrenergic, noncholinergic nerve stimulation. PMID- 1612357 TI - Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. AB - Short-chain fatty acid irrigation has been shown to ameliorate inflammation in diversion colitis. In this study the effect of butyrate enemas was tested in 10 patients with distal ulcerative colitis who had been unresponsive to or intolerant of standard therapy for 8 weeks. They were treated for 2 weeks with sodium butyrate (100 mmol/L) and 2 weeks with placebo in random order (single blind trial). Before and after treatment, clinical symptoms were noted and the degree of inflammation was graded endoscopically and histologically. Rectal proliferation was assessed by autoradiography. After butyrate irrigation, stool frequency (n/day) decreased from 4.7 +/- 0.5 to 2.1 +/- 0.4 (P less than 0.01) and discharge of blood ceased in 9 of 10 patients. The endoscopic score fell from 6.5 +/- 0.4 to 3.8 +/- 0.8 (P less than 0.01). The histological degree of inflammation decreased from 2.4 +/- 0.3 to 1.5 +/- 0.3 (P less than 0.02). Overall crypt proliferation was unchanged, but the upper crypt-labeling index fell from 0.086 +/- 0.019 to 0.032 +/- 0.003 (P less than 0.03). On placebo, all of these parameters were unchanged. These data support the view that butyrate deficiency may play a role in the pathogenesis of distal ulcerative colitis and that butyrate irrigation ameliorates this condition. PMID- 1612358 TI - The role of angiotensin in the intestinal vascular response to hypotension in a canine model. AB - It was previously shown that the vasoconstrictory response to hypotension was similar in the mucosa of the small bowel and the colon but was significantly higher in the muscularis of the latter than that of the former. To understand the mechanism of this differential response of the muscularis of the small bowel and the colon, the present study investigated the effect of an angiotensin II inhibitor (saralasin) on the hypotension-induced vasoconstriction of the mucosa and the muscularis of these two locations of the gastrointestinal tract. Dogs were used. Hypotension was induced by hemorrhage to reduce blood pressure by 40 mm Hg. Blood flow was measured by 15-microns radiolabeled microspheres. Saralasin was infused intravenously for 20 minutes at a rate of 0.05 mg.kg-1 bolus followed by 1 microgram.kg-1.min-1. Saralasin had no effect on the basal blood flow of the mucosa or the muscularis of the small bowel or on the hypotension-induced vasoconstriction of these two layers of the small bowel. In contrast, saralasin decreased blood flow to the mucosa (-28%; P less than 0.001) and increased blood flow to the muscularis (+140%; P less than 0.001) of the colon under basal conditions and also reduced the hypotension-induced vasoconstriction of the colonic muscularis (P less than 0.01). These and supplementary data indicate that there is a difference between the small bowel and the colon in local activity of vascular angiotensin system and that this system is most active in the colonic muscularis where it plays a significant role in the vasoconstrictory response to hypotension. PMID- 1612359 TI - Effect of erythromycin on gastric motility in controls and in diabetic gastroparesis. AB - The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase 3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications. PMID- 1612360 TI - Right and left colonic transit after eating assessed by a dual isotopic technique in healthy humans. AB - Propulsion of colonic contents after eating in the whole colon was studied in 15 volunteers by scintigraphy with injection of 111In-diethylenetriamine-pentaacetic acid and 99mTc-sulfur colloid into the colon through a nasogastric tube. The radionuclide was injected into the cecoascending colon (n = 7), the hepatic flexure (n = 6), the splenic flexure (n = 9), and the descending colon (n = 4). Changes of activity in the regions distal from and proximal to the injection points were determined before and after a 1000-kcal meal. Isotopic movements were also analyzed when a simultaneous injection of the two markers in the right and left parts of the colon was achieved (n = 11). During fasting, no significant change of activity was seen. After eating, radioactivity injected into the cecoascending and the hepatic flexure was transferred distally (P less than 0.01 and P = 0.07); radioactivity injected into the splenic flexure was transferred both distally (P = 0.07) and proximally (P less than 0.02); and no significant change of activity was seen proximally from or distally to the descending colon. Both antegrade and retrograde isotopic movements increased after eating (P less than 0.01), but the number of antegrade movements was significantly greater (P less than 0.05). This study confirms the colonic propulsive effect of eating and shows that this response is different in the right and left parts of the colon. PMID- 1612361 TI - Neurotensin stimulates growth of colonic mucosa in young and aged rats. AB - Neurotensin, a tridecapeptide widely distributed in the gut, stimulates growth of small bowel mucosa in young and aged rats. In the present study, the effect of long-term neurotensin administration on the growth of colonic mucosa was examined in young (2-month-old) and aged (24-month-old) rats. Subcutaneous injections of saline (control) or neurotensin (300 micrograms/kg) in gelatin were given to the groups of rats every 8 hours for 10 days. During treatment, all rats were maintained on a regular chow diet. Rats were killed on day 11; the entire colon was removed, mucosa was scraped and weighed, and DNA, RNA, and protein contents were determined. Neurotensin induced growth of colonic mucosa in both age groups. In young rats, neurotensin increased weight and DNA, RNA, and protein contents of colonic mucosa. The ratio of DNA content, an index of cellular hyperplasia, was increased significantly in the neurotensin-treated young rats compared with age matched controls, indicating an overall increase in mucosal cellularity. In the aged rats, growth was characterized by an increase in weight and RNA and protein contents, but not DNA content, thus suggesting cellular hypertrophy. These results suggest that neurotensin has an important regulatory function in the growth of colonic mucosa; however, the mode of action, at the cellular level, appears to be different depending on age. PMID- 1612362 TI - Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. AB - The results of three small clinical trials examining the effect of calcium carbonate supplementation on the proliferation cytokinetics of the rectal epithelium in subjects with a current history of sporadic adenoma are reported. In six subjects, a daily administration of 1500 mg of calcium carbonate for 90 days failed to significantly suppress thymidine labeling in normal-appearing mucosa of the rectum. However, a daily dose of 2000 mg of calcium significantly (P = 0.008) altered mucosal proliferation in a second set of six subjects after a 30-day trial. Finally, a placebo-controlled trial of calcium (2000 mg) was conducted in which 20 subjects were randomized to groups receiving a 4-week intervention with calcium (or placebo), followed by the alternative treatment (placebo or calcium). The results of the study show a marked suppression of rectal proliferation during the calcium phase of the study but not during the placebo phase. This study adds to accumulating evidence showing that calcium supplementation regulates the proliferative behavior of colonic epithelium in the individual at high risk for colon cancer. Longer term trials of calcium supplementation will ascertain whether a continuing benefit from increasing dietary calcium translates into inhibition of adenoma recurrence. PMID- 1612363 TI - Expression of an elongation factor 1 gamma-related sequence in adenocarcinomas of the colon. AB - The authors have previously reported that a messenger RNA (mRNA) bearing 60% homology to elongation factor 1 gamma in Artemia salina was overexpressed in 7 of 9 pancreatic tumors relative to normal appearing adjacent tissue. The purpose of the present study was to determine if this pattern of overexpression is also detected in colorectal carcinoma. Overexpression was observed in 25 of 29 colorectal carcinomas, relative to normal adjacent tissue. Of them, mRNA was overexpressed in 2 tumors classified as Dukes' D, in 8 of 11 tumors classified as Dukes' B2, and in 15 of 16 tumors classified as Dukes' C2. PMID- 1612364 TI - Metallic self-expanding stent application in the upper gastrointestinal tract: caveats and concerns. AB - Ten patients with a variety of upper gastrointestinal tract stenoses precluding conventional prostheses or associated with recurrent occlusions of these prostheses, had an expandable metal Z stent placed. All patients had successful insertion (esophagus, five; biliary, three; afferent loop, one; efferent loop, one), although there was a tendency for the prostheses to delivery distally (gut) or proximally (biliary tree). Despite patency rates for up to 6 months in the esophagus and 1 year in the biliary tree, additional data and design modifications are required before widespread utilization. PMID- 1612365 TI - Esophageal hematoma and tear from a taco shell impaction. PMID- 1612366 TI - Endoscopic removal of an impacted colonic foreign body (fish bone) complicated by a pelvic abscess. PMID- 1612367 TI - Post-sclerotherapy intramural esophageal hematoma: endoscopic and radiologic findings. PMID- 1612368 TI - Superficial gastric cancer and severe mucosal dysplasia in Barcelona. PMID- 1612370 TI - Diagnostic efficiency of an ultra-rapid endoscopy room test for Helicobacter pylori. PMID- 1612369 TI - Incomplete pancreas divisum associated with abnormal junction of pancreaticobiliary duct system. PMID- 1612371 TI - Incidence of heterotopic gastric mucosa in the upper esophagus. PMID- 1612372 TI - Endoscopic stenting for post-operative biliary strictures. AB - This study evaluates the efficacy of endoscopic stenting in 70 patients with noncomplete post-operative biliary strictures. The treatment consisted of placement of two 10 F gauge straight endoprostheses with elective exchange trimonthly, for a 1-year period. Successful endoprosthesis placement was accomplished in 66 of 70 patients (94%). In all 66 patients jaundice subsided. During the stenting period six patients had an operation and six died. In 46 patients the endoprostheses were removed. The mean period of follow-up was 42 months (range, 4 to 99 months). Excellent (asymptomatic, normal, or stable liver enzymes) and good (only one episode of cholangitis) responses were achieved in 83%; restricturing occurred after stent removal in 17%. Prolonged biliary stenting appears to be a safe and effective treatment modality for benign post operative strictures and a valid alternative to surgery. PMID- 1612373 TI - Endoscopic transpapillary catheterization of the gallbladder followed by external shock wave lithotripsy and solvent infusion for the treatment of gallstone disease. AB - Herein we describe the techniques and early results of attempted endoscopic transpapillary catheterization of the gallbladder (ETCG) in combination with external shock wave lithotripsy (ESWL) and solvent infusion in the treatment of 23 consecutive, symptomatic patients with gallstones. Despite anticipated difficulty in advancing wires and catheters through the cystic duct, impeded by tortuosity of its lumen, ETCG was successfully accomplished in 20 of the 23 patients (86.9%). Through an indwelling catheter, obstructed gallbladders were drained in 4 patients and combined treatment with ESWL and infused solvents was carried out in 18 patients. Combined treatment resulted in elimination of gallstones from the gallbladders of 14 of 18 patients (77.7%). Treatment was complicated by mild pancreatitis in only 1 of 20 successfully catheterized patients; there was no mortality. PMID- 1612374 TI - Long-term costs after gastroenterology consultation with endoscopy versus radiography in dyspepsia. AB - A randomized clinical trial assessed the medical costs during 6 months after the evaluation of dyspepsia by gastroenterology consultation with esophagogastroduodenoscopy versus barium radiography. Primary care physicians entered patients whose dyspepsia responded incompletely to empiric therapy or recurred. The consultation/endoscopy group (N = 32) was similar (p greater than 0.23) to the radiography group (N = 34) regarding age, gender, physician visits, and costs of all dyspepsia drugs and H2 blockers during 6 months before evaluation. Most patients had non-ulcer dyspepsia. Costs during the succeeding 6 months (consultation/endoscopy versus radiography groups) were physician visits ($33.1 +/- 14.5 vs. $114.2 +/- 23.3, p less than 0.005); radiologic procedures ($70.5 +/- 37.3 vs. $67.6 +/- 22.5, p greater than 0.30); all dyspepsia drugs ($30.4 +/- 10.0 vs. $100.1 +/- 36.8, p = 0.08); H2 blockers ($25.4 +/- 9.5 vs. $96.0 +/- 34.7, p = 0.06); and total cost ($134.0 +/- 43.8 vs. $435.3 +/- 93.9, p = 0.006). The higher total cost in the radiography group was partly due to the referral of 7 patients (21%) for gastroenterology consultation due to persistent dyspepsia, 6 of whom had endoscopy versus the performance of radiography in 0 of the 32 consultation/endoscopy patients (p less than 0.025). Dyspepsia self ratings were similar. PMID- 1612375 TI - Endoscopic ultrasonography compared with computed tomography with ERCP in patients with obstructive jaundice or small peri-pancreatic mass. AB - Pre-operative assessment of a potentially resectable peri-pancreatic mass by computed tomography (CT) is widely used, but often of limited value for lesions less than 5 cm. ERCP is frequently used to evaluate those patients with associated obstructive jaundice. To determine the clinical effectiveness of endoscopic ultrasonography (EUS), patients with pancreatobiliary lesions of less than 5 cm with or without obstructive jaundice were evaluated. CT scan, ERCP, and EUS were performed on 60 patients with a peri-pancreatic mass and/or obstructive jaundice. The results of the examinations were compared with respect to detection of an abnormality, diagnosis, and prediction of resectability. ERCP and EUS were the most sensitive and specific in detecting an abnormality of the pancreatobiliary system. The accuracy of EUS compared with the accuracy of the combination of CT scan with ERCP was significantly higher for the evaluation of the specific type and extent of pancreatobiliary disease (73% vs. 30%, p less than 0.001) and prediction of resectability (75% vs. 38%, p less than 0.05). EUS aided patient management in 75% by providing more details about the disease, and changed management in 32% by making a diagnosis or changing an incorrect diagnosis. EUS represents a significant advance in the evaluation and clinical management of pancreatobiliary disease. PMID- 1612376 TI - Endoscopic ultrasonography as an adjunct to fine needle aspiration cytology of the upper and lower gastrointestinal tract. AB - Twenty consecutive patients with either extrinsic or submucosal masses or gastric ulcers suspicious for malignancy with previously negative conventional forceps biopsies and/or brush cytology underwent a combined approach of endoscopic ultrasound (EUS) followed by fine needle aspiration cytology. Diagnostic results were obtained in 17 of 20 patients. The three patients with indeterminate aspirates had EUS findings strongly supportive of the final diagnosis. EUS combined with fine needle aspiration cytology appears to be of value in the evaluation of extrinsic, submucosal, and ulcerative lesions of the gastrointestinal tract. PMID- 1612377 TI - Combustible colonic gas levels during flexible sigmoidoscopy and colonoscopy. AB - To what extent the standard preparation for sigmoidoscopy (phosphosoda enemas) makes the bowel safe for electrocautery is unknown. Sixty patients were prospectively evaluated to compare the presence of the combustible gases hydrogen and methane during colonoscopy and flexible sigmoidoscopy. Thirty patients underwent flexible sigmoidoscopy after phosphosoda enema preparation, and 30 patients underwent colonoscopy after a polyethylene glycol solution preparation. During colonoscopy, the concentrations of hydrogen and methane remained below combustible levels in all patients. Even segments of colon with significant fecal matter present did not have combustible levels of these two gases. However, at flexible sigmoidoscopy, combustible levels of hydrogen and methane were measured in 3 of 30 (10%) patients. Due to the risk of explosion, electrocautery should not be performed during routine flexible sigmoidoscopy after the standard phosphosoda enema preparation. PMID- 1612378 TI - The role of endoscopy after vertical banded gastroplasty. AB - Since 1984, a total of 99 patients underwent vertical banded gastroplasty (VBG) through protocol (pouch 8 ml in size, band 4.3 cm in circumference) to treat morbid obesity. Follow-up was obtained in 95 patients. Thirty upper gastrointestinal endoscopies were performed post-operatively in 17 patients. Indications were nausea/vomiting in 11, epigastric pain in 4, acute obstructive symptoms in 4, and miscellaneous in three. Findings included food impaction in 10, distal esophagitis in 8, gastritis in 4, and a normal examination in 2. Only 4 of 10 food impactions were associated with an excessively narrowed gastroplasty outlet. Eight patients had an excessively narrowed gastric stoma: two became asymptomatic with dietary modification only and six underwent dilation therapy (dilator range from 8 to 18 mm in diameter) with immediate resolution of symptoms in four of six. One of the two patients unresponsive to dilation was lost to follow-up, and the other required surgical revision after multiple dilation sessions. PMID- 1612379 TI - Pentagastrin given during upper gastrointestinal endoscopy: a simple screening method for hypo- and achlorhydria. PMID- 1612380 TI - Catheter-guided endoscopic intubation: a new technique for intubating a difficult esophagus. PMID- 1612381 TI - Hepatic intra-arterial methylene blue injection during endoscopy: a method of detecting gastroduodenal misperfusion in patients receiving hepatic intra arterial chemotherapy via an implanted pump. PMID- 1612382 TI - Diagnostic and therapeutic jejunoscopy with a new, longer enteroscope. PMID- 1612383 TI - Endoscopic therapy of a duodenal duplication cyst. PMID- 1612384 TI - Endoscopic drainage of a duodenal duplication cyst. PMID- 1612385 TI - Common bile duct and gallbladder varices. PMID- 1612386 TI - Small bowel obstruction in a patient with Peutz-Jeghers syndrome: the role of intraoperative endoscopy. PMID- 1612387 TI - Blue rubber bleb nevus syndrome: gastrointestinal involvement and its endoscopic presentation. PMID- 1612388 TI - Visceral leishmaniasis in AIDS with gastric involvement. PMID- 1612389 TI - Biliary stent migration with colonic diverticular impaction. PMID- 1612390 TI - Training in gastrointestinal endoscopy. PMID- 1612391 TI - Advanced training in gastrointestinal endoscopy. PMID- 1612392 TI - The ASGE/FDA study on complications of sedation. PMID- 1612393 TI - Meperidine-associated bronchospasm. PMID- 1612394 TI - Atropine for colonoscopy: no benefit. PMID- 1612395 TI - Parotid swelling after upper gastrointestinal endoscopy. PMID- 1612396 TI - Gastric syphilis: an unusual endoscopic appearance. PMID- 1612397 TI - Gastric Kaposi's sarcoma without skin lesions presenting as linitis plastica. PMID- 1612398 TI - Hematochezia associated with the watermelon rectum. PMID- 1612399 TI - Percutaneous endoscopic gastrostomy placement in the morbidly obese. PMID- 1612400 TI - Aquatosis coli after irrigation with a heater probe catheter. PMID- 1612401 TI - Acute tension pneumoperitoneum following colonoscopy. PMID- 1612403 TI - [The value of prepartal ultrasound estimation of birth weight in breech presentation]. AB - Biometric data, i.e. the biparietal (BPD) and fronto-occipital diameter (FOD) of the skull as well as the transverse (TTD) and the longitudinal trunk diameter (LTD) were obtained in 127 cases of breech and 95 cases of vertex presentations within one week before birth. These data were compared with the birth weight measured postpartally. From these data, an optimized equation was derived for both breech and vertex presentations and compared to the equation known from the literature. The optimized equation for breech presentations requires only the biometric data of the trunk (TTD and LTD). In spite of this optimization, the quality of the foetal weight estimation of breech presentations seems to be more inaccurate in comparison to the estimation of vertex presentations. Concerning the obstetrical management the foetal weight estimation by ultrasound has to be evaluated more critically for breech presentations than for vertex presentations. PMID- 1612402 TI - [Reducing the incidence and morbidity of very low birth weight premature infants after maternal transport to a perinatal center]. AB - An improvement in the mortality and morbidity of very low-birth-weight infants could be confirmed by the regionalisation of high-risk pregnancies. The immaturity of premature newborn limits the therapeutic success. Our aim is therefore on the one hand, to make an early diagnosis of patients at risk of threatened premature delivery, and secondly, to provide intensive therapy for women already showing symptoms of premature delivery, to achieve the best possible prognosis. A reduction in the number of very low birth-weight infants and their mortality and morbidity rate appears to be possible if the pregnant women can be placed in a perinatal centre in good time; if the pregnancy can be prolonged and fetal lung maturation can be induced by betamethasone; if the delivery can be managed carefully, avoiding hypoxaemia, shock situations, and trauma; in certain cases this would mean performing a caesarean section by isthmo cervical longitudinal incision; if primary neonatal care is performed by an experienced neonatologist. With the standard of neonatology as it is today, a considerable increase in the survival rates of very low birth-weight infants can hardly be expected. Nevertheless, to cut down their numbers is the biggest potential for the future reduction of the infant mortality rate. PMID- 1612404 TI - [Placental morphometry in diastolic zero and negative flow of the umbilical arteries]. AB - Macromorphometric and histometric placental data, in cases with enddiastolic zero flow or reverse flow (dZRF), reveal a lower placental weight and smaller attachment area as well as bigger terminal villi with a reduced amount of epithelial plates with comparable vascularisation. In cases with reverse flow, all parameters were worse, either compared to the controls or to the zero flow cases. With advancing duration of clinical observation, we find a maturation of the terminal villi, with the cross-sectional areas getting smaller, diffusion distances becoming shorter and vessels bigger. This proves the dependence of foetal outcome by dZRF on the compensatory capacity of the terminal villi. The planimetric area in the forward flow channel depends on the foetal intravillous blood volume. PMID- 1612405 TI - [Doppler ultrasound of the umbilical artery in fetuses with sonographically abnormal findings and/or chromosome abnormalities (corrected)]. AB - We performed 77 Doppler blood flow studies of the umbilical artery in 45 foetuses with malformations and/or chromosomal abnormalities. 20 foetuses had chromosomal abnormalities and 34 records of the second and third trimester were analysed. In 25 foetuses with malformations, but without chromosomal abnormalities, 43 investigations were performed between 21st and 40th weeks of gestation. In the second trimester, 3 of 11 foetuses with chromosomal abnormalities had an absence of enddiastolic flow velocities, whereas the other foetuses had pulsatility indices within the range for foetuses with a normal karyotype. In the third trimester, 7 of 10 foetuses with chromosomal abnormalities had pathological Doppler findings. Four cases had absent or reversed enddiastolic (ARED) flow velocities. Altogether 10 of 13 foetuses beyond the 19th weeks of gestation had pathological Doppler findings (sensitivity = 77%). The structure and the function of the placenta is influenced by the abnormal karyotype, which is demonstrated by pathological Doppler findings. Only 3 of 43 investigations in foetuses with malformations but normal karyotype, showed abnormal PI values and there was no case of ARED flow. In a group of 24 foetuses with ARED flow, 6 foetuses had chromosomal abnormalities. All foetuses with malformations and ARED flow had an abnormal karyotype. Prenatal chromosome analyses of foetuses with suspicious sonographic findings, revealed a rate of 29% chromosomal abnormalities, nearly all of them with a maternal age under 35 years. Whereas Doppler sonography cannot exclude chromosomal abnormalities before the 20th weeks of gestation, there is a good correlation between chromosomal abnormalities and abnormal Doppler findings later on.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612406 TI - [Incidence and type of premenstrual symptoms in relation to experienced infertility: a comparative study]. AB - Using the symptomatological criteria of "Late Luteal Dysphoric Disorder" according to DSM-III-R, the frequency and type of premenstrual symptoms were investigated in a group of 405 infertile women (participants in an in-vitro fertilisation programme at the University of Bonn) and a control group of 101 female medical students. 84% of both groups of women reported premenstrual psychological and/or physical changes. 52% of the infertile patients and 42% of the students fulfilled the symptomatological criteria of late luteal dysphoric disorder. Comparing both groups, it was found, that infertile women reported significantly more often mood lability, anger/irritability, anxiety/tension and loss of interest. PMID- 1612407 TI - [Results of a prognosis study of in vitro fertilization after brief psychotherapy]. AB - During the last four years, our research has been focussed on prediction criteria for IVF after a Short Course of psychotherapy. Our study can be divided in two phases: In an earlier phase (up to 1990), prediction criteria were derived from "expert" rating, whereas in a later phase (from 1990 onwards) they were derived by self-rating of the patients. The predictions refer to changes in the patients' behaviour, affective state, mood and attitude (acronym: BAMA) towards their infertility. Our work is based on the hypothesis, that a perceivable change in BAMA and in how the patients relate to their wanting a child, represents the solution of the problem, which facilitates the consequential events of either pregnancy or acceptance of childlessness or else adoption. As a rule, the absence of such a change entails none of the consequential events. - We report on and discuss the results of the earlier, as well as the later phase and finally compare them as to how well they correlate with prediction and consequences. A marked correlation could be found between changes in BAMA and the occurrence of pregnancy or acceptance of childlessness in both phases of our study. Comparing the two phases (expert- vs. self-rating) on the accuracy of prediction, we could find almost identical results. Because of the easier and more economical application of self-rating we decided to continue with this method and to refine it for further research. PMID- 1612408 TI - [Round-headed spermatozoa--contraindication for IVF]. AB - A couple is presented suffering from primary sterility for 20 years and who were selected for an IVF test, since conservative methods failed to induce a pregnancy. The ejaculate of two semen samples revealed exclusively round-headed spermatozoa in each sample. Contrary to this diagnosis, however, asthenoteratozoospermia had been diagnosed in previous investigations and the patient had been treated with tamoxifene. However, no therapy exists for the phenomenon of round-headed spermatozoa, because this defect is genetic of origin and correlates with irreversible infertility. PMID- 1612409 TI - ["Hospital tourism". Case report of Munchausen syndrome]. AB - We report on a 29-year old patient, who was treated as an inpatient in 95 different hospitals (altogether 173 times) within 7 years. The gynaecologist can suspect Munchausen's syndrome, if the following aspects are recorded: dramatic clinical admissions patterns, (frequently out of the normal consultation time); a history of several operations and many short stays in different hospitals. Special care in diagnostics should be taken to avoid further unnecessary surgical interventions. PMID- 1612410 TI - [Christian Gerhard Leopold (1846-1911)]. AB - Christian Gerhard Leopold was one of the outstanding German gynaecologists at the turn of this century. Although interested in the entire discipline of obstetrics and gynaecology including related areas, he is merely known today for his obstetrical manoeuvres. Under his chairmanship, the Dresden Royal Gynaecological Infirmary developed into a leading hospital in Germany. Leopold died on September 12, 1911, following a heart attack. PMID- 1612411 TI - Identification of Casuarina-Frankia strains by use of polymerase chain reaction (PCR) with arbitrary primers. AB - Free-living N2-fixing Frankia strains isolated from Casuarina sp. were investigated for genomic polymorphism. We used six 10-mer oligonucleotides as single arbitrary primers (AP) for the polymerase chain reaction (PCR) in order to amplify random DNA fragments in the genome of free-living Frankia strains. Agarose-gels of the amplified genomic DNA revealed that two of the six arbitrary primers showed polymorphism in the eight different Frankia genomes. Analysis of the AP-PCR products showed 9 polymorphic bands ranging from 4.1-0.60 kb. We conclude that single arbitrary primers can be used to amplify genomic DNA, and that polymorphism can be detected between the amplification products of the different Frankia genomes. PMID- 1612412 TI - Nucleotide sequence of the methoxyneurosporene dehydrogenase gene from Rhodobacter sphaeroides: comparison with other bacterial carotenoid dehydrogenases. AB - The nucleotide sequence of the 1794-bp fragment containing the crtD gene from Rhodobacter sphaeroides 2.4.1 encoding for methoxyneurosporene dehydrogenase has been determined. A 63% sequence identity was found when compared with the nucleotide sequence of the crtD gene from Rhodobacter capsulatus. A putative regulatory palindromic motif present in the crtD gene from R. capsulatus also exists in this gene from R. sphaeroides. The translated open reading frame of the crtD gene of R. sphaeroides has identified a polypeptide of 495 amino acids which shares a 56% sequence identity with the same CrtD protein of R. capsulatus. The N and C-termini of these CrtD proteins present a high degree of similarity with the N- and C-termini of other carotenoid dehydrogenases including those encoded by crtI genes. This is in good agreement with the previously hypothesized homology between CrtI and CrtD proteins. PMID- 1612413 TI - Fatty acid alterations in Saccharomyces cerevisiae exposed to ethanol stress. AB - The influence of ethanol concentration on fatty acid alterations in total phospholipids (PL), phosphatidylcholine (PCH), phosphatidylethanolamine (PE), phosphatidylinositol (PI), sterol esters (ES) and triacylglycerols (TAG) of Saccharomyces cerevisiae was studied. Ethanol induced the elevation of palmitic and oleic acid level in major membrane phospholipids (PCH and PE) and also the palmitoleic acid content in ES and TAG. PMID- 1612414 TI - Nucleotide sequence of the extracellular alpha-amylase gene in the yeast Schwanniomyces occidentalis ATCC 26077. AB - The Schwanniomyces occidentalis (formerly castellii) ATCC 26077 (CBS 2863) alpha amylase (AMY 26077) gene was cloned in Saccharomyces cerevisiae and sequenced. An open-reading frame encoding the AMY consists of 1536 base pairs and contains 512 amino-acid residues, which is almost the same in size as the AMY of Sch. occidentalis ATCC 26076 and CCRC 21164. The amino-acid sequence of AMY 26077 differed from that of ATCC 26076 alpha-amylase (AMY 26076) at two residues and from that of CCRC 21164 alpha-amylase (AMY 21164) at three residues. Comparison of the AMY 26077 gene with its homologues from two other strains (Sch. alluvius CBS 1153 and Sch. persoonii CBS 2169) using several restriction enzymes revealed that the AMY 26077 was very similar to AMY CBS 1153 but different from that of CBS 2169. PMID- 1612415 TI - Cloning and expression of Staphylococcus epidermidis urease gene sequences in Staphylococcus carnosus. AB - The urease gene sequences of Staphylococcus epidermidis CNS23 were cloned and expressed in Staphylococcus carnosus TM300. In vitro translation of the cloned sequences revealed four polypeptides (60, 17, 11 and 7.5 kDa) that were associated with enzyme activity. Southern hybridisation experiments showed high homologies with the urease genes of Staphylococcus saprophyticus. PMID- 1612416 TI - Growth of Haemophilus influenzae type b in continuous culture: effect of dilution rate on outer-membrane protein and lipopolysaccharide expression. AB - Haemophilus influenzae type b (Hib) was grown in continuous culture under cystine limitation between dilution rates (D) of 0.065-0.28 h-1. A similar outer-membrane protein profile, as adjudged by SDS-PAGE, was found at all dilution rates. However, a shift to a lipopolysaccharide structure with a greater electrophoretic mobility on SDS-PAGE with accompanying changes in monoclonal antibody reactivity was observed at D greater than or equal to 0.15 h-1. Growth rate per se can affect the expression of outer-membrane components of Hib. PMID- 1612417 TI - Purification and characterisation of an NAD(+)-dependent secondary alcohol dehydrogenase from Pseudomonas maltophilia MB11L. AB - A constitutive NAD(+)-linked alcohol dehydrogenase was purified 338-fold from cells of Pseudomonas maltophilia MB11L grown on glucose. Maximum activity was observed with cyclic and linear secondary alcohols, with little activity seen against primary or aromatic alcohols. Substrate oxidation activity was maximal at pH 10.0, while substrate reduction was optimal at pH 4.5. The Km values for propan-2-ol, NAD+ and acetone were 87, 413 and 143 microM respectively. The enzyme is a tetramer with subunit Mr of approximately 44,000. It has an isoelectric point of 4.75, and was inhibited by chelating agents, thiol reagents and certain metal ions. PMID- 1612418 TI - Nitrogen regulation of fatty acids and avermectins biosynthesis in Streptomyces avermitilis. AB - Fatty acid composition was analysed in the producer of avermectins, Streptomyces avermitilis C-18 grown in chemically defined medium with different nitrogen sources. Significant differences in nitrogen regulation of fatty acid biosynthesis were found in this strain in comparison with other streptomycetes studied so far. This finding could be explained at the level of regulation of branched-chain amino acid metabolism. PMID- 1612419 TI - Analysis and expression of the Borrelia burgdorferi P/Gau fla gene: identification of heterogeneity with the B31 strain. AB - The flagellin gene from the P/Gau strain of Borrelia burgdorferi was cloned and sequenced. The translated P/Gau flagellin protein differed from the flagellin of the B31 strain at 13 of 336 amino acids. This includes seven differences between amino acids 190-234, an immunodominant and specific region for B. burgdorferi. The entire flagellin molecule, as well as peptides of the internal portion of the protein which is more specific for B. burgdorferi, has been expressed in Escherichia coli using a pET7HIS.2 expression system. These peptides may be of great value for the development of sensitive and specific recombinant-based serological assays. PMID- 1612420 TI - Location of catalase in crystalline peroxisomes of methanol-grown Hansenula polymorpha. AB - We have studied the intraperoxisomal location of catalase in peroxisomes of methanol-grown Hansenula polymorpha by (immuno)cytochemical means. In completely crystalline peroxisomes, in which the crystalline matrix is composed of octameric alcohol oxidase (AO) molecules, most of the catalase protein is located in a narrow zone between the crystalloid and the peroxisomal membrane. In non crystalline organelles the enzyme was present throughout the peroxisomal matrix. Other peroxisomal matrix enzymes studied for comparison, namely dihydroxyacetone synthase, amine oxidase and malate synthase, all were present throughout the AO crystalloid. The advantage of location of catalase at the edges of the AO crystalloids for growth of the organism on methanol is discussed. PMID- 1612421 TI - Isolation and characterization of tributyltin chloride-resistant marine Vibrio. AB - Tributyltin chloride (TBTCl)-resistant marine bacteria were isolated from coastal sea water. One of these bacteria (Vibrio M-1) was highly resistant when grown in medium containing 125 microM of TBTCl. This strain was sensitive to other metals. Two polypeptides, 30 kDa and 12 kDa, increased when the strain was cultured in the medium supplemented with TBTCl. Initially TBTCl was taken up by the cell; however, the amount of TBTCl determined in the cellular fraction was low after the exponential growth phase of Vibrio M-1, suggesting the existence of a TBTCl efflux system. PMID- 1612422 TI - A DNA-probe for the detection of the species Staphylococcus haemolyticus. AB - A 1.3-kb DNA fragment isolated from Staphylococcus haemolyticus strain DSM 20264 can be used as a specific probe for this species. The probe hybridized with 39 clinical isolates of S. haemolyticus but not with any of the 121 isolates representative of the other 25 species of staphylococci described to date. PMID- 1612423 TI - Lantibiotic-mediated anti-lactobacillus activity of a vaginal Staphylococcus aureus isolate. AB - Staphylococcus aureus strain 26 inhibited the growth of 23 of 26 lactobacilli of endocervical origin, but only two of 17 staphylococci, in deferred antagonism tests. The inhibitory agent, a bacteriocin-like inhibitory substance (BLIS) named staphylococcin Au-26, was obtained from vigorously shaken liquid cultures containing a 0.1% (v/v) supplement of Tween 80 and was purified by chromatographic fractionation on XAD-2, carboxymethyl Sephadex and reversed phase HPLC. The molecular mass of staphylococcin Au-26 was estimated by SDS-PAGE to be approx. 2700. The detection of lanthionine residues in the molecule, the high stability to heating at acidic but not alkaline pH values and inactivation by proteinases indicate that staphylococcin Au-26 is a member of the lantibiotic class of peptide antibiotics--the first reported to be produced by a S. aureus strain. Primary sequence analysis showed that the N-terminus of the molecule is isoleucine, a characteristic also displayed by the lantibiotics nisin, epidermin and gallidermin. PMID- 1612424 TI - Secondary aminoglycoside resistance in aminoglycoside-producing strains of Streptomyces. AB - The role of aminoglycoside (AG) acetyltransferases (AACs) and of the corresponding genes in resistance to foreign AGs in AG-producing strains of Streptomyces were studied. The research focussed on (i) the activation mechanism of the cryptic kanamycin(Km)-resistance-encoding gene that encodes an AAC(3) in streptomycin-producing S. griseus SS-1198, and (ii) an AAC(2') with novel activity and substrate specificity in kasugamycin-producing S. kasugaensis MB273. Activation of the cryptic kan gene in S. griseus SS-1198 is probably due to a single base substitution at the putative -10 promoter region, leading to the enhancement of transcription, resulting in resistance to AG. The coding region of the kan gene was highly homologous to that of the aacC7 gene of paromomycin producing S. rimosus forma paromomycinus. On the other hand, resistance in S. kasugaensis MB273 was found to be due to an AAC(2') capable of acetylating astromicin group AGs at two different sites (1-NH2 with istamycin B, and 2'-NH2 with astromicin and istamycin A). These additional antibiotic resistances that are independent of a self-resistance basis may be regarded as 'secondary' resistances, so as to distinguish them from 'primary' resistances arising from a self-resistance basis. PMID- 1612425 TI - Complex organization of the Streptomyces avermitilis genes encoding the avermectin polyketide synthase. AB - The avermectin (Av) polyketide synthase (PKS) and erythromycin (Er) PKS are encoded by modular repeats of DNA, but the genetic organization of the modules encoding Av PKS is more complex than Er PKS. Sequencing of several related DNA fragments from Streptomyces avermitilis that are part of the Av biosynthetic gene cluster, revealed that they encode parts of large multifunctional PKS proteins. The Av PKS proteins show strong similarity to each other, as well as similarity to Er PKS proteins [Donadio et al., Science 252 (1991) 675-679] and fatty acid synthases. Partial DNA sequencing of the 65-kb region containing all the related sequence elements in the avr genes provides evidence for twelve modular repeats encoding FAS-like domains. The genes encoding the Av PKS are organized as two sets of six modular repeats which are convergently transcribed. PMID- 1612427 TI - Glutamine synthesis in Streptomyces--a review. AB - The synthesis of glutamine synthetase (GS), a key enzyme in ammonium (NH4+) assimilation, is regulated by nitrogen availability in several Streptomyces strains. In addition, the enzymatic activity of the GS enzyme is post translationally regulated by adenylylation. Nitrogen regulation of GS synthesis is mediated at the transcriptional level in S. coelicolor, and transcription of the GS structural gene (glnA) requires a positive regulatory protein, GlnR. The amino acid sequence of the GlnR protein is similar to that of the Escherichia coli positive regulatory proteins, OmpR and PhoB, which belong to the family of bacterial two-component regulatory systems. DNA encoding a GSII-like enzyme has been cloned from S. viridochromogenes and S. hygroscopicus, but the role of this GS isoenzyme in NH4+ assimilation in Streptomyces is unclear. PMID- 1612426 TI - Identification and characterization of phosphinothricin-tripeptide biosynthetic genes in Streptomyces viridochromogenes. AB - A 4-kb BamHI fragment of Streptomyces viridochromogenes Tu494 carrying phosphinothricin-tripeptide (PTT) biosynthetic genes has been identified by complementation of a nonproducing mutant which is defective in the tripeptide formation step. Nucleotide sequence analysis revealed one incomplete and three complete genes on the cloned fragment. The incomplete gene ('pms) codes for the C terminus of the phosphinomethylmalic acid synthase as determined by comparison with a region from the bialaphos biosynthetic cluster [Shimotohno et al., Agric. Biol. Chem. 54 (1990) 463-470] and with databases. Subcloning experiments showed that the juxtaposing phsA gene is sufficient to restore productivity of the blocked mutant. Analysis of gene disruption and gene replacement mutants confirmed that phsA specifies an enzyme involved in tripeptide formation. Similarities to peptide synthetases indicate that the condensation step follows a thio-template mechanism. A conserved region located in the C terminus of the PhsA protein showed identity to 4'-phosphopantetheine-binding sites of fatty acid and polyketide synthases. In the N terminus, a typical acyl transfer motif has been identified and this may be involved in transthiolation. A similar motif also appears in the deduced product of the third gene (dea), which probably catalyses the deacetylation of N-acetyl-PTT to PTT. The previously described PTT resistance encoding gene (pat) was located between the phsA and the dea genes. PMID- 1612428 TI - Secondary metabolism, inventive evolution and biochemical diversity--a review. AB - Evidence now being obtained through nucleotide (nt) sequence analysis supports the concept that secondary metabolism has arisen by modification of existing primary metabolic reactions. Although amino acid sequence identity deduced from nt sequences of genes encoding proteins from related primary and secondary metabolic pathways is sufficient to indicate a common ancestry, the match is often better when genes in different rather than in the same species are compared. The information so far available suggests that gene transfer between organisms has been an important factor in the evolution of secondary metabolism. Many secondary pathways may be of relatively ancient origin and they may have arisen only infrequently. Much subsequent elaboration of the pathways has probably taken place after their acquisition by other species and so has been influenced by a variety of selective conditions. The characteristic diversity of secondary metabolites and their functions can be accounted for by the random manner in which the pathways initially evolved and have subsequently been exploited. PMID- 1612429 TI - The expanded horizon for microbial metabolites--a review. AB - Modern screening methods have been used for a variety of new natural products. By taking advantage of the side effects of erythromycin, a derivative, EM523, and several related substances (motilides) have been synthesized. These compounds are agonists of the peptide hormone, motilin. By screening for microbial metabolites which may substitute for biologically active peptides, we discovered lactacystin. It has nerve growth-factor-like activity and induces differentiation in mouse neuroblastoma Neuro2A cells. An inhibitor of protein kinase, staurosporine, a microbial alkaloid found by chemical screening, has a variety of pharmacological activities, such as the relaxation of rabbit aortic strips and the inhibition of changes in platelet shape induced with phorbol myristate acetate. Triacsin, an inhibitor of acetyl-CoA synthetase, which was isolated from Streptomyces sp. SK 1894, potentiated platelet-activating factor production of A23187-treated rat polymorphonuclear leukocytes. Phthoxazolin, an inhibitor of cellulose biosynthesis isolated from Streptomyces sp. OM-5714, inhibited the growth of velvet leaf when treated after its emergence. These products provide examples of the possible utility of newly discovered microbial metabolites. PMID- 1612430 TI - The evolutionary role of secondary metabolites--a review. AB - It is argued that organisms have evolved the ability to biosynthesise secondary metabolites ('natural products') due to the selectional advantages they obtain as a result of the functions of the compounds. Pleiotropic switching, the simultaneous expression of sporulation and antibiotic biosynthesis genes in Streptomyces, is interpreted in terms of the defense roles of antibiotics. The clustering together of antibiotic biosynthesis, regulation, and resistance genes, and in particular the staggering complexity shown in the case of the gene cluster for erythromycin A biosynthesis, implies that these genes have been selected as a group and that the antibiotics function in antagonistic capacities in nature. PMID- 1612431 TI - Secondary metabolites as chemical signals for cellular differentiation. AB - Several microbial secondary metabolites function as essential chemical signals for induction of cellular differentiation in the producing organisms. The role of A-factor and its analogues such as essential autoregulators in actinomycetes is discussed and a review is given of fungal metabolites with hormonal activities. Divergent secondary metabolites with the capability to induce cellular differentiation in other organisms are also discussed as to their possible involvement in a symbiotic relationship in the ecosystem. PMID- 1612432 TI - Regulation of secondary metabolism and cell differentiation in Streptomyces: A factor as a microbial hormone and the AfsR protein as a component of a two component regulatory system. AB - A-factor is a microbial hormone that functions as a key switch for secondary metabolite formation and morphogenesis in Streptomyces griseus. Genetic and biochemical studies on the A-factor-binding protein have implied that the binding protein present in the cytoplasm plays a role in repressing streptomycin (Sm) production and sporulation while the binding of A-factor to the binding protein releases this repression. The A-factor signal is transferred, probably via some additional regulatory proteins in the A-factor-regulatory cascade, to the strR gene, a regulator for Sm biosynthesis. A positive regulatory protein binds about 430-330 bp upstream from the transcription start point of the strR promoter and activates its transcription. The StrR product, in turn, activates the other Sm biosynthesis genes. A global regulatory gene, afsR, of Streptomyces coelicolor A3(2) encodes a 993-amino acid protein that is phosphorylated by a specific phosphokinase, AfsK, encoded by the region just upstream from the afsR gene. Site directed mutagenesis of afsR has revealed that phosphorylated AfsR globally stimulates transcription of antibiotic-production genes. It is most likely that AfsR and AfsK compose a two-component regulatory system. Although AfsR shows no significant homology with typical regulators of the two-component systems in other prokaryotes, such as OmpR and PhoB of Escherichia coli, it shows considerable homology with regulatory proteins in antibiotic biosynthetic gene clusters of Streptomyces spp., such as actII ORF4, dnrR1 ORF1 and redD ORF1.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612433 TI - Molecular analysis of sporulation in Streptomyces griseus. AB - Previous evidence suggested that orf1590 from Streptomyces griseus has the potential to encode two polypeptide products from temporally regulated nested open frames (orfs) and that the longer polypeptide may be a DNA-binding protein. We have developed a hypothetical model of the role of orf1590 in sporulation of S. griseus and have begun to test this model by determining the nucleotide sequence of the orf1590 counterpart from Streptomyces coelicolor. The conservation of the helix-turn-helix domain and the two potential translation start codons is consistent with our model. Continued analysis of bald mutants of S. griseus has indicated that several prematurely synthesize sporulation septa and spore walls. One of these nonsporulating strains appears to be a bldA mutant of S. griseus. Complementation analysis suggests that at least three genetic loci are involved in the correct timing of deposition of sporulation septa and wall thickening. PMID- 1612434 TI - The possible role of ADP ribosylation in physiological regulation of sporulation in Streptomyces griseus. AB - The role of ADP ribosylation of proteins in the physiological regulation of sporulation in Streptomyces griseus was studied. We report here that both the activity of NAD+: arginine ADP-ribosyltransferase (ADPRT) and the pattern of ADP ribosylated proteins showed characteristic changes during the life cycle in S. griseus 2682. Analysis off ADP-ribosylated proteins revealed that in a nonsporulating mutant of the parental wild-type (wt) strain (Bld7 mutant), both the activity of ADPRT and the pattern of ADP-ribosylated proteins were different from those of the parental strain. Addition of 3-aminobenzamide (3AB), the most potent inhibitor of ADPRT, inhibited sporulation of S. griseus 2682 and the A factor (AF)-induced sporulation of S. griseus Bld7, but in both cases the inhibitory effect of 3AB was strictly age-dependent. Using [alpha-32P]GTP, we have demonstrated the presence of GTP-binding proteins in purified cell membranes of S. griseus 2682 and S. griseus Bld7. The same GTP-binding proteins were observed in Bld7 and the wt. AF stimulated the basal GTPase activity of cell membranes of S. griseus 2682 in a concentration-dependent manner, suggesting that GTP-binding proteins might be involved in the AF-induced sporulation process. PMID- 1612435 TI - Actinomycetes as agents of biodegradation in the environment--a review. AB - The diversity of form in the Actinomycetales is well-recognised, due to the sustained generation of environmental isolates for pharmaceutical screening. Actinomycetes isolated from soil and related substrates show primary biodegradative activity, secreting a range of extracellular enzymes and exhibiting the capacity to metabolise recalcitrant molecules. Composting is one process which relies heavily on such prolific actinomycete activity. Amongst actinomycetes in soil, there are examples of different strategies, from cycles of rapid proliferation and sporulation to the maintenance of populations by prolonged slow growth and scavenging, and the evidence for this is examined. The mechanisms of lignocellulose degradation by actinomycetes are discussed in relation to functional conservation within the group, and correlations with those described in other bacteria and fungi. PMID- 1612436 TI - Histidine ammonia-lyase from Streptomyces griseus. AB - Histidine ammonia-lyase (histidase; HutH) has been purified to homogeneity from Streptomyces griseus and the N-terminal amino acid (aa) sequence used to clone the histidase-encoding structural gene, hutH. The purified enzyme shows typical saturation kinetics and is inhibited competitively by D-histidine and histidinol phosphate. High concentrations of K.cyanide inactivate HutH unless the enzyme is protected by the substrate or histidinol phosphate. On the basis of the nucleotide sequence, the hutH structural gene would encode a protein of 53 kDa with an N terminus identical to that determined for the purified enzyme. Immediately upstream from hutH is a region that strongly resembles a class of Streptomyces promoters active during vegetative growth; however, there is no obvious ribosome-binding site adjacent to the hutH translation start codon. The deduced aa sequence of an upstream partial open reading frame shows no similarity with other proteins, including HutP of Bacillus subtilis and HutU of Pseudomonas putida. Promoter-probe analysis indicates that promoter activity maps within the DNA surrounding the hutH start codon. Pairwise comparisons of the primary structures of bacterial and mammalian histidases, together with the unique kinetic properties and gene organization, suggest that streptomycete histidase may represent a distinct family of histidases. PMID- 1612437 TI - Gene transfer between streptomycetes in soil. AB - The growth and activity of Streptomyces violaceolatus and Streptomyces lividans was studied in soil under controlled conditions. The life cycle was followed under differing nutrient regimes and the fate of plasmid- and phage-borne genes determined by direct and indirect techniques. Methods were developed for the direct monitoring of plasmid DNA extracted from soil which allowed differentiation of the cellular location of plasmid DNA between mycelium and spores. In a dynamic, nutrient-fed soil microcosm, inoculants survived poorly, but a specific stage was defined by direct and indirect methods when the inoculants were most active and this correlated with the detection of gene transfer events. Plasmid transfer, phage infection and lysogeny only occurred to a significant extent within this stage at days 15-17 during a 60-day incubation. Estimates based on plasmid DNA recovery indicated that viable counts underestimated spore and mycelial propagules by a factor of greater than 100. PMID- 1612438 TI - Actinomycete infections in humans--a review. AB - Diseases caused by pathogenic aerobic and facultatively anaerobic actinomycetes differ considerably with respect to their etiology, pathogenesis, clinical appearance and epidemiology. Facultatively anaerobic (fermentative) actinomycetes may not only be involved etiologically in the three classical forms of cervicofacial, thoracic and abdominal actinomycoses, but also in infections of the female genital organs, the eye, the tissue adjacent to dental implantation elements and tooth extraction wounds. The species distribution of the fermentative actinomycetes isolated from these conditions varied to a certain, but characteristic, extent, as did the concomitant actinomycotic flora. The sex ratio reported for human Actinomyces infections (male:female = 3:1) appeared to be restricted to actinomycotic abscesses and empyemas. The prevailing pathogenic, obligately aerobic actinomycete species in Germany was found to be Nocardia farcinica followed by Nocardia asteroides. The comparatively high incidence of N. farcinica infections was chiefly due to the occurrence of nosocomial postoperative wound infections by this pathogen observed in two German hospitals. Besides surgical treatment, immunosuppressive treatment appeared to be the most common factor predisposing for nocardiosis. Recent observations strongly suggested that the spectrum of human nocardial infections in Germany has been changing, as regards the overall incidence, the prevalence of N. farcinica, the sex ratio, the mean age of patients, as well as the role of N. farcinica as a possibly important nosocomial pathogen. PMID- 1612439 TI - Nocardia as a pathogen of the brain: mechanisms of interactions in the murine brain--a review. AB - Nocardia asteroides strain GUH-2 invades the brain without inducing an early inflammatory response in normal mice. This strain can grow within the neurons as well as adjacent areas causing neurological damage without abscess formation. At low inoculum doses, this organism is gradually cleared from the brain after the initial burst of growth. Therefore, at two weeks, the brains of these mice appear to become sterile, but the animals begin to develop a variety of neurological signs including an L-dopa responsive headshake. It was found that mice that recovered from sublethal infection with N. asteroides strain GUH-2 had progressive and permanent neuron damage in regions of the brain, the extent of which appeared to correlate with specific neurological signs. The mechanisms of this response are not known, but current data indicate that the level of nonspecific phagocyte activation (microglia?) within the brain represents an important first line of defense. Next, T-lymphocytes are important in the secondary response in the brain to nocardial invasion. Finally, B-lymphocytes and a humoral immune response may be involved in these complex interactions; however, it is not clear how these responses relate to the permanent and progressive brain damage induced by Nocardia. It is possible that these latter responses may exacerbate neurodegeneration. PMID- 1612440 TI - Immunodiagnosis of nocardiosis. AB - A specific immunodominant 54-kDa antigen was purified from a culture filtrate of Nocardia asteroides by immunoaffinity chromatography. The chromatography column was prepared with immunoglobulin G obtained from sera from patients with lepromatous leprosy. Unbound solutes consisted of specific, partially purified N. asteroides antigens, primarily a 54-kDa band, accompanied by two others of 31 and 62 kDa. The Western blot (immunoblot) technique was applied to detecting the immunologic response to nocardiae in the serum of nocardiosis patients. Each of the serum samples from immunosuppressed or immunocompetent patients infected with N. asteroides reacted with the 54-kDa band, and two reacted with the 31- and 62 kDa bands. There was no reaction to either the 54- or the 31-kDa antigen with all serum samples obtained from patients with tuberculosis, except for one, with all serum samples obtained from patients with leprosy, or with all sera obtained from healthy controls. The partially purified 54-kDa antigen, specific for N. asteroides, was used as the immunogen to generate monoclonal antibodies (mAbs) and two mAbs were selected. As determined by Western blot, both mAbs reacted with the 54-kDa band. Using indirect immunofluorescence or enzyme immunoassay with whole N. asteroides micro-organisms, the mAbs did not react with N. asteroides cells. No cross-reactivity with mycobacterial antigens, either culture-filtrate antigens or tuberculin, was exhibited with any of the two mAbs. These mAbs are candidates to be used for the development of a sensitive and specific diagnostic test for nocardiosis. PMID- 1612441 TI - Numerical classification and identification of Streptomyces species--a review. AB - Evidence is presented to show that numerical taxonomy is of proven value both for the circumscription and identification of Streptomyces species. In addition, 252 representatives of numerically defined species and species-groups of this taxon were examined for 273 unit characters and the resultant data analysed using conventional statistics. Clustering was only marginally affected by the proximity coefficients used or by test error, estimated at 3.37%. The numerical classification obtained confirmed and extended the results of previous taxometric surveys, notably by showing that the Streptomyces albidoflavus species-group encompassed taxospecies corresponding to S. albidoflavus, Streptomyces anulatus and Streptomyces halstedii. Rapid enzyme tests based upon the fluorophores, 7 amino-4-methylcoumarin and 4-methylumbelliferone, provide useful data for streptomycete systematics. It can be concluded that the genus Streptomyces is currently well circumscribed and underspeciated. PMID- 1612442 TI - Pyrolysis mass spectrometry as a method for the classification, identification and selection of actinomycetes. AB - Pilot experiments were designed to determine the potential of Curie-point pyrolysis mass spectrometry (PyMS) in the classification, identification and typing of industrially significant actinomycetes, and for the detection of target and novel actinomycetes needed for pharmacological screening programmes. The results indicate that the method is of value for the separation of actinomycetes at and below the species level, in the detection and circumscription of novel actinomycetes, and for the detection of identical and duplicated strains. There is also evidence that the pyrolysis system will permit the identification of target actinomycetes directly from selective isolation plates. PyMS is one of the methods that should be used to generate polyphasic taxonomies of actinomycete genera. PMID- 1612443 TI - Phage typing--a useful tool in actinomycete systematics. AB - A total of 905 strains of several genera of the Actinomycetales were tested in respect to their sensitivity to genus- and species-specific actinophages. The results provided clear evidence that phage typing is a useful aid for the identification of actinomycetes. At the genus level, the specificity of actinophages has led to the correct placement of falsely identified strains, as well as to the rearrangement of genera. At the species level, however, phage typing has been less successful: only some actinophages are available so far, lysing strains (often not all) of one or a few related species (synonyms), e.g., of the genera Streptomyces and Amycolatopsis, as well as Saccharopolyspora. PMID- 1612444 TI - DNA-DNA hybridization in the systematics of Streptomyces. AB - The DNA relatedness among strains in several different phenotypically defined Streptomyces species clusters was evaluated. It was found that the data from DNA relatedness studies do not necessarily agree with the clustering generated using numerical taxonomic techniques. A study of the morphologically heterogeneous 'S. cyaneus' cluster showed that morphological criteria traditionally used to classify and identify Streptomyces species still have value, since strains in DNA relatedness cluster groups were also similar morphologically (i.e., they had similar spore color, surface properties, and sporophore morphology). An evaluation of DNA relatedness among strains in the S. violaceusniger and S. lavendulae clusters indicated that, if anything, the genus is underspeciated, based on the number of single-member clusters observed. A study of strains of the sweet potato pathogen, S. ipomoea, collected in various locations in the United States and Japan indicated, not surprisingly, that all of the strains belong to the same species. PMID- 1612445 TI - Ribosomal RNA and rDNA sequence analyses. AB - The potential of ribosomal (r) RNA and the encoding genes (rDNA) to elucidate natural relationships has been dramatically extended by improved sequencing approaches and the application of polymerase chain reaction. Sequence information on 16S and 23S rRNA/DNA from 69 strains of 53 Streptomyces species allows determination of regions that can be used as target sites for diagnostic probes, and for amplification and sequencing primers. To generate phylogenetic trees, sequence similarities are converted into distance values. The topologies of the trees based on different parts of the molecule are compared among each other and to the numerical phenotypic clustering of the strains. PMID- 1612446 TI - Polyacrylamide gel electrophoresis analysis of ribosomal protein: a new approach for actinomycete taxonomy. AB - The ribosomal (r)-proteins from eleven Streptomyces strains representing various numerical taxonomic clusters were compared by two-dimensional polyacrylamide-gel electrophoresis (2D-PAGE). The protein patterns were specific for each species. An attempt was made to identify one strain of Streptomyces by both traditional taxonomic methods and 2D-PAGE analysis of the r-protein patterns. Both methods identified the strain as Streptomyces lavendulae, and protein pattern analysis also showed that S. griseolavendus was a variant of S. lavendulae. Actinomycete r protein AT-L30 exhibited electrophoretic mobility that is specific for each genus. On the basis of this observation, we analyzed AT-L30 r-proteins from numerous strains of species belonging to the genera Actinomadura, Microtetraspora, Streptosporangium, Nocardia, Rhodococcus and mycolate-less wall chemotype-IV actinomycetes. The results strongly supported the conclusions of previous work and thus proved the efficacy of r-protein analysis as a novel approach for taxonomy of actinomycetes. PMID- 1612447 TI - Regulation and secretion of an extracellular esterase from Streptomyces scabies. AB - Production of a heat-stable, extracellular esterase by Streptomyces scabies is regulated by zinc ions. The esterase-encoding gene (est) from S. scabies was cloned and expressed in Streptomyces lividans. In S. lividans, expression of the est gene is also regulated by Zn2+, and the esterase is efficiently secreted in this organism. The sequence of the est gene suggests that a 39-amino acid signal peptide is removed during secretion of this protein. Deletion analysis has indicated that the hydrophobic domain of the signal peptide is required for secretion. Gel retardation assays and DNaseI footprinting using an S-30 protein extract from S. scabies have previously identified a specific 23-bp protein binding site upstream from the est coding sequence. Deletion of this protein binding sequence significantly decreased expression of the est gene. PMID- 1612449 TI - Genetic instability in Streptomyces ambofaciens: inducibility and associated genome plasticity. AB - DNA amplification and deletions occur at high frequency in unstable regions localized on the Streptomyces ambofaciens chromosome. The structure of these regions was investigated, leading to the identification of internal reiterations which could play a role in the deletion and/or amplification mechanism(s). UV irradiation and treatments with mitomycin C, oxolinic acid and novobiocin were shown to efficiently induce genetic instability. Finally, mutator strains were isolated, in which genetic instability was dramatically increased. The involvement of an SOS-like response in genetic instability in S. ambofaciens is proposed. PMID- 1612448 TI - Gene expression in the Streptomyces temperate phage phi C31. AB - The repressor gene, c, of the temperate Streptomyces phage, phi C31 was previously cloned and sequenced, and predicted to encode a 74-kDa protein. The c gene actually produces three in-frame, N-terminally different, C-terminally identical proteins of 74, 54 and 42 kDa. The repressor proteins are translated from a corresponding nest of transcripts. Genetic and biochemical evidence suggests that the transcription of the c locus is autoregulated possibly by the 42-kDa protein binding to a highly conserved 16-bp perfect inverted repeat. The 16-bp sequence is present at at least twelve loci throughout the phi C31 genome. Transcription of the 'early' region is complex, possibly involving phage-specific promoters. The phi C31 terminators display sequence conservation and may be regulated. The phi C31 gene 'k' may encode a nucleotide kinase-encoding gene. PMID- 1612450 TI - Molecular genetic analysis of proline and tryptophan biosynthesis in Streptomyces coelicolor A3(2): interaction between primary and secondary metabolism--a review. AB - We studied the control of proline metabolism and tryptophan biosynthesis in Streptomyces coelicolor A3(2), because proline is involved in secondary metabolism [undecylprodigiosin (Red) biosynthesis] whilst tryptophan, to our knowledge, is not. Proline transport was constitutive in wild-type cells, as were the enzymes of proline catabolism. When we analysed proline biosynthesis, we discovered that growth in the presence of proline stimulated rather than repressed the biosynthetic genes. We isolated proline transport mutants and to our surprise discovered that such strains overproduced Red. As well as losing the ability to transport proline, they had lost, to differing extents, the ability to degrade proline. However, proline biosynthesis appeared to be unaffected. It appears that proline anabolism and catabolism in S. coelicolor A3(2) is in a state of dynamic equilibrium and that if this balance is disturbed, Red biosynthesis can act as a sink for excess proline. We cloned the trpD and the trpCBA clusters of S. coelicolor A3(2) and identified a promoter within the latter cluster. This promoter appeared not to be regulated by the presence or absence of exogenous tryptophan, but rather by the growth phase and/or the growth rate of the culture. It appears, therefore, that an amino acid biosynthetic pathway that is apparently not involved in secondary metabolism in the streptomycete is regulated at the genetic level--not by feedback repression, but rather by the overall physiological state of the cell. PMID- 1612451 TI - Identification of Streptomyces coelicolor genes involved in regulation of antibiotic synthesis. AB - To define genetic elements that regulate antibiotic synthesis, we screened for mutations that visibly blocked synthesis of Streptomyces coelicolor's two pigmented antibiotics and found mutant strains in which all four antibiotics were blocked. The responsible mutations defined two loci, absA and absB. Two additional approaches to defining genes have been taken: isolation of cloned genes with a dominant negative effect on antibiotic synthesis and isolation of genes which, in multicopy, can compensate for specific mutational blocks. These genes apparently function in a global regulatory pathway (or network) for control of antibiotic synthesis. PMID- 1612453 TI - A novel, highly efficient gene-cloning system in Micromonospora applied to the genetic analysis of fortimicin biosynthesis. AB - We have developed a gene-cloning system in Micromonospora olivasterospora, a fortimicin A (astromicin) producer. Plasmids of Micromonospora from two strains of M. olivasterospora were used for construction of the vectors. Two antibiotic resistance genes, nmrA and nmrB, cloned from a neomycin-producing Micromonospora, were introduced into these plasmids for the selection of transformants. In a new protoplasting protocol for lysozyme-resistant bacteria, protoplasts of M. olivasterospora were found in short-time incubation with lysozyme and transformed efficiently, indicating that the method was suitable to shotgun cloning. Using this system, seven biosynthetic genes for fortimicin A were cloned. Their physical maps revealed that at least four of these genes were clustered. Analysis of a cosmid library of M. olivasterospora showed that eleven biosynthetic genes and a self-defense gene existed in a region of approx. 25 kb of DNA. PMID- 1612452 TI - Resistance to macrolides and lincosamides in Streptomyces lividans and to aminoglycosides in Micromonospora purpurea. AB - Ribosomal (r) resistance to gentamicin in clones containing DNA from the producing organism Micromonospora purpurea is determined by grmA, and not by kgmA as originally reported. The kgmA gene originated in Streptomyces tenebrarius and is identical to kgmB. Both grmA and kgm encode enzymes that methylate single specific sites within 16S rRNA, although the site of action of the grmA product has not yet been determined. In either case, the methylated nucleoside is 7 methyl G. Inducible resistance to lincomycin (Ln) and macrolides in Streptomyces lividans TK21 results from expression of two genes: lrm, encoding an rRNA methyltransferase and mgt, encoding a glycosyl transferase (MGT), that specifically inactivates macrolides. The lrm product monomethylates residue A2058 within 23S rRNA (Escherichia coli numbering scheme) and confers high-level resistance to Ln with much lower levels of resistance to macrolides. Substrates for MGT, which utilises UDP-glucose as cofactor, include macrolides with 12-, 14 , 15- or 16-atom cyclic polyketide lactones (as in methymycin, erythromycin, azithromycin or tylosin, respectively) although spiramycin and carbomycin are not apparently modified. The enzyme is specific for the 2'-OH group of saccharide moieties attached to C5 of the 16-atom lactone ring (corresponding to C5 or C3 in 14- or 12-atom lactones, respectively). The lrm and mgt genes have been cloned and sequenced. The deduced lrm product is a 26-kDa protein, similar to other rRNA methyltransferases, such as the carB, tlrA and ermE products, whereas the mgt product (deduced to be 42 kDa) resembles a glycosyl transferase from barley.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612455 TI - Biosynthesis of the erythromycin macrolactone and a rational approach for producing hybrid macrolides. AB - The three eryA genes involved in the formation of the polyketide portion of the macrolide antibiotic erythromycin in Saccharopolyspora erythraea, appear to be organized in a single transcriptional unit on the basis of the results of gene disruption experiments. An insertion sequence-like element of lower G + C content separates eryAI from eryAII. The organization of the enzymatic domains present in the eryA-encoded multifunctional polypeptides, determined by computer-assisted analysis, is presented. This has enabled the determination of a putative dehydratase domain. A rational approach for producing novel macrolides by introducing selected changes in polyketide synthase genes is outlined. The isolation of a lactone intermediate resulting from an early synthesis step in macrolactone formation is also presented. PMID- 1612454 TI - Sequence similarity between macrolide-resistance determinants and ATP-binding transport proteins. AB - The three macrolide-resistance-encoding genes, tlrC from Streptomyces fradiae, srmB from Streptomyces ambofaciens, and carA from Streptomyces thermotolerans, encode proteins that possess significant sequence similarity to ATP-dependent transport proteins. The N-terminal and C-terminal halves of these proteins are very similar to each other and contain highly conserved regions that resemble ATP binding domains typically present within the superfamily of ATP-dependent transport proteins. These observations suggest that the mechanism by which these genes confer resistance to macrolides is due to export of the antibiotics, a process that is driven by energy derived from ATP hydrolysis. PMID- 1612456 TI - Cerebral atrophy precedes the change in cerebral blood flow in patients with ischemic cerebrovascular disease: a short-term follow-up study. AB - Cerebral atrophy and the decrease in cerebral blood flow (CBF) progress with advancing age. Which of them takes first place, the changes in CBF or cerebral atrophy? We investigated longitudinal changes in CBF and cerebral atrophy in 14 patients with ischemic cerebrovascular disease (CVD): 11 patients with supratentorial lacunar infarction and 3 with carotid transient ischemia attack who were neurologically stable during the 1-3 years of observation. Cerebral atrophy was estimated by the brain atrophy index (BAI): one of the CT area measurement methods, and CBF was measured using the 133Xe inhalation technique. While significant progression of cerebral atrophy was observed, there was no significant change in CBF. Cerebral atrophy precedes the change in CBF and CVD. PMID- 1612457 TI - Nutritional status in recently hospitalized and free-living elderly subjects. AB - Weight index (WI), triceps skinfold (TSF), serum albumin and delayed cutaneous hypersensitivity reaction (DCH) were measured in 96 hospitalized elderly patients and in 100 age- and sex-matched free-living controls. Using the 10th percentile of data obtained in the controls, WI was subnormal in 35% of the patients. Corresponding findings with regard to TSF, serum albumin and DCH were 32, 50 and 31%, respectively. The findings in the controls were mainly within the range observed in national reference groups. Patients were considered malnourished if they showed at least two variables (of which one was required to be anthropometric) below the cut-off limits used. When these limits were set at the 10th percentile of the recordings in the controls, the occurrence of undernutrition in the patients was 39%. By using the 5th percentile the corresponding figure was 16%. Malnourishment was most pronounced in patients with multiple organ disease and malignancy. It is concluded that low nutritional indices are a common occurrence in elderly subjects admitted to hospital and that undernutrition is related to the nature of the disease rather than age. PMID- 1612458 TI - Prevalence and causes of anaemia in a geriatric hospitalized population. AB - Of 732 consecutive patients admitted to an acute geriatric ward, 178 (24%) were found to be anaemic (haemoglobin of 115 g/l or below). An appropriate cause responsible for anaemia was identified in 83%. The anaemia of chronic disorders (ACD) (35%) and iron deficiency anaemia (15%) were the commonest causes. The spectrum of disorders associated with ACD is much broader than the classical category of infectious, inflammatory and malignant disorders. The relatively high prevalence of the myelodysplastic syndrome (5%) is striking and this syndrome as a cause of anaemia in geriatric patients deserves more attention than it has so far received. No obvious cause was found in 17%. The clinical significance of this finding remains unclear. PMID- 1612459 TI - Lead accumulation in the bones of aging male mice. AB - The lead content of mouse femurs increased by 83% between 76 and 958 days of age with values ranging from 0.192 to 1.78 ng Pb/mg dry weight. These values are remarkably lower than in previous reports for the lead content of bone. The lead content of mouse liver showed no aging-related trend with values ranging from 0.00823 to 0.0149 ng/mg dry weight. Bone density, calcium and collagen content were not related to the lead content. We conclude that while bone lead content is very low in mice, it increases with aging but does not appear to be related to the osteopenia which develops in the C57BL/6J male mouse. PMID- 1612460 TI - Modelling survivorship kinetics: a two-parameter model. AB - A mathematical model of survivorship kinetics is presented. It takes into account both deterministic and stochastic aspects of survival curves. Earlier reports [Piantanelli: Arch Gerontol Geriatr 1986;5:107-118; Piantanelli: Ann NY Acad Sci 1988; 521:99-109] described a model capable of making distinct predictions on the mean and standard deviation of an index of physiological function, fitting data even in the tail of survivorship curves, and accounting for the selection of the cohort at advanced ages. However, it contains four parameters whose biological interpretation is unclear. In the present paper we propose a modification of the model which maintains the main characteristics of the previous one and, in addition, results in two significant improvements. First, the number of free parameters is reduced to only two, making much easier both their estimation and interpretation, particularly when the model is applied to data from various animal groups manipulated in different ways. Second, it is possible to relate the parameters to well-defined deterministic and stochastic factors: specifically, a deterministic component describing the environmental and genetic influence on physiological functions, and a stochastic component representing the fluctuating interactions of the living organism and its environment. PMID- 1612461 TI - Low-level chemiluminescence and life span of Drosophila melanogaster. AB - Spontaneous photon emission (chemiluminescence, CL) as a monitor of free radical evolution in Drosophila melanogaster which had been maintained at 25 or 30 degrees C for 5 days after emergence was measured. When maintained at 30 degrees C the fly CL intensity was stronger than at 25 degrees C. Under the condition of the higher temperature, the fly life span was shorter (mean life span = 29 days at 30 degrees C and 63 days at 25 degrees C), and oxygen consumption (3.7 microliters/mg.h at 25 degrees C, 4.9 microliters/mg.h at 30 degrees C) and the mobility (movement distance = 25 mm/min at 25 degrees C, 700 mm/min at 30 degrees C) increased, together with augmentation of phospholipid hydroperoxide in the fly total lipids. The CL spontaneously emitted from fly homogenate was decreased by the free radical scavengers both in experiments in vivo and in vitro. The hypothesis is proposed that as the oxygen metabolism grows active, the chemiluminescent reactions that involve oxygen-dependent free radical metabolism, including membrane phospholipid hydroperoxidation, contribute to the acceleration of senescence of fly bodies. PMID- 1612462 TI - Hypergravity and aging in Drosophila melanogaster. 4. Climbing activity. AB - Drosophila melanogaster flies climb up the sides of their vial after having been submitted to a mechanical stimulation; that ability is impaired at older ages. The climbing activity (CLI) of flies kept at various gravity levels (1, 3 and 5 g) has been measured throughout life, in cross-sectional studies. Hypergravity had no effect on CLI at young age, but older flies kept in hypergravity displayed lower scores than flies kept at 1 g. Results are discussed in relation with the hypothesis of increased aging rate in hypergravity. PMID- 1612463 TI - Hypergravity and aging in Drosophila melanogaster. 5. Patterns of movement. AB - The paths of young, middle-aged and old Drosophila melanogaster flies, kept at various gravity levels (1-5 g) throughout life, have been recorded in a cross sectional study. Aging flies exhibit more sinuous paths and do not move as far away from their release point as younger ones. These age-related changes in the patterns of movement are expressed at younger ages in flies submitted to hypergravity. As for the climbing activity experiment, the patterns of movement do not clearly vary with the gravity level at young age. Results are discussed in relation to the hypothesis of increased aging rate in hypergravity. PMID- 1612464 TI - Hypergravity and aging in Drosophila melanogaster. 6. Spontaneous locomotor activity. AB - The spontaneous locomotor activity (SLA) of Drosophila melanogaster flies kept at various gravity levels (1-5 g) was recorded in both longitudinal and cross sectional experiments. No gravity level effect could be detected in the longitudinal one, probably because these flies were allowed (for technical reasons) to rest at 1 g for 15% of their life. By contrast, flies kept at 5 g in the cross-sectional experiment had lower SLA scores at middle and old age than both 1 and 3 g-kept flies. The results of this series of experiments on hypergravity (HG) effects on three forms of locomotor activity (climbing activity, patterns of movement and SLA) allow to conclude that aging is accelerated in HG, even if no longevity decrease could be detected in the 1-4 g range. PMID- 1612465 TI - Syndromes of aging. AB - Syndromes of aging are classified according to the rate of their development and the sequence of aging of different systems within an organism. Syndromes of aging are characterized by individual and populational specifics. Determination of syndromes of accelerated aging or retarded aging permits the prediction of age pathology development and life span. Comparison of aging peculiarities in animals with different species-specific life spans permits the definition of species specific changes, chronobiological changes that correlate with chronobiological age, ontobiological changes that correlate with biological age, and parameters that do not change with age. Different correlation of the above parameters forms the basis for species-specific variations in the aging process. Neurohumoral shifts observed in aging are identical to stress effects, and therefore may be referred to as the stress-age syndrome. PMID- 1612466 TI - Calcemic status of geriatric patients: a longitudinal study. AB - Serum ionized (CaI), total (CaT) and albumin-'corrected' total (CaA) calcium concentrations were measured in 108 geriatric long-term inpatients on admission and again 37 months (mean) later. Mean CaI, especially when pH adjusted, remained extremely stable, indicating well-preserved homeostatic calcemic control even in the terminal years in the elderly. Further, the results indicate that in addition to their previously shown invalidity in interindividual comparisons, CaT and CaA are inferior to CaI and can also be misleading in the detection of slight longitudinal changes in the 'true' calcemic status of an individual geriatric patient. PMID- 1612467 TI - Antioxidant-influenced alterations in glutathione reductase activity in different age groups of male mice. AB - The glutathione reductase activity was estimated in brain and liver of male mice of different age groups fed on butylated hydroxy anisole (BHA), propyl gallate (PG) and alpha-tocopherol (TP). A significant increase in glutathione reductase activity was observed with TP during all the phases (pre-reproductive, reproductive and post-reproductive). Antioxidants enhanced the enzyme activity in both the tissues with the exception of BHA in brain during reproductive and PG in liver during pre-reproductive phases respectively. The enhanced reducing potential of the cell in terms of added bioconversion of GSSG to GSH may account for increase in longevity on antioxidant treatment. PMID- 1612468 TI - Respiration and heart rate variability during sleep in untreated Parkinson patients. AB - Twenty-six patients with untreated mild to moderate Parkinson's disease (PD) lasting 5 years or less, were investigated in the sleep laboratory. Sleep architecture and respiration during sleep did not significantly differ from age matched controls. PD patients showed defective cardiac autonomic control during sleep, mainly parasympathetic but also sympathetic in nature, although they had normal results in conventional autonomic tests during wakefulness. Therefore, autonomic cardiac involvement seems to be an early sign of PD. PMID- 1612469 TI - Ambulatory blood pressure monitoring as a means to avoid overtreatment of elderly hypertensive patients. AB - Do elderly similarly to younger hypertensive patients tend to be overtreated if therapeutic decisions are based exclusively on blood pressure measured by the physician in his office? Eighteen hypertensive patients (10 previously treated) aged 70 years or more had repeatedly office systolic blood pressure greater than or equal to 170 mm Hg and/or diastolic blood pressure greater than or equal to 100 mm Hg. The physicians in charge were asked to reduce blood pressure within 4 months to a target of less than or equal to 160/95 mm Hg using any drug regimen. Blood pressure was monitored during daytime using a noninvasive blood pressure recorder, but the results of the recording were not available to the physicians until the end of the study. At the outset, 11 patients had a mean ambulatory recorded blood pressure less than 170/100 mm Hg. Those patients who exhibited high blood pressures only in the doctor's presence did not reduce their ambulatory blood pressure when antihypertensive therapy was initiated or intensified in order to reduce office blood pressure. This contrasted with the significant fall in ambulatory blood pressure observed in the presence of the doctor. Thus ambulatory blood pressure monitoring seems useful to avoid overtreatment not only of younger but also of elderly hypertensive patients. PMID- 1612470 TI - Molecular biology and coeliac disease. PMID- 1612471 TI - Strategies for hepatitis B immunisation. PMID- 1612472 TI - Site and mechanism of pain perception with oesophageal balloon distension and intravenous edrophonium in patients with oesophageal chest pain. AB - Ten healthy volunteers and 13 patients with oesophageal motility disorders whose primary presenting complaint was chest pain were studied by distending an intraoesophageal balloon in 1 ml steps to the point of a sensation of discomfort. The net balloon pressure (intra-balloon pressure when inflated within the oesophagus minus the pressure recorded at the same volume outside the patient) was measured at each volume increment and the distension volume at the perception of discomfort was noted. The measurements were repeated after intravenous injection of edrophonium (80 micrograms/kg) and again after 1.2 mg intravenous atropine. Oesophageal wall compliance was similar in patients and controls, and the two groups showed a similar effect of decreased compliance with edrophonium and increased compliance after atropine. There were no significant differences between patients and controls of distending volume at perception of discomfort. Edrophonium, however, resulted in a significant reduction in distension threshold for pain (p less than 0.03) in patients. A similar though non-significant trend was seen in controls. In both controls and patients, distension volume for pain production after atropine was significantly (p less than 0.01) higher than after edrophonium. From these results and other published data, we suggest that the pain receptor for noxious stretch and after edrophonium challenge is likely to be an 'in series' mechanoreceptor located in oesophageal longitudinal muscle. PMID- 1612473 TI - Subtypes of intestinal metaplasia and Helicobacter pylori. AB - To determine whether there is a relationship between the presence of H pylori and the various subtypes of intestinal metaplasia in the gastric antrum, 2274 antral gastroscopic biopsies from 533 patients were examined. H pylori was found in 289 patients. Intestinal metaplasia in general was found in 135 patients. Type I intestinal metaplasia was found in 133 patients (98.5%), type II in 106 patients (78.5%) and type III in 21 patients (15.6%). Ninety eight of these 135 patients (72.6%) were H pylori positive and 37 patients (27.4%) were H pylori negative. No statistically significant difference was found in the prevalence of type I and II intestinal metaplasia between the intestinal metaplasia positive and H pylori positive and intestinal metaplasia negative and H pylori negative patients. Type III intestinal metaplasia was found less often in the intestinal metaplasia positive and H pylori positive patients (11.2%) as compared with intestinal metaplasia positive and H pylori negative patients (27%) (p less than 0.05). In contrast with type I and II intestinal metaplasia type III intestinal metaplasia was found more often in moderate/severe intestinal metaplasia than in mild intestinal metaplasia (p less than 0.02). Within the group of patients with moderate/severe intestinal metaplasia, type III was found less often in the H pylori positive patients (p less than 0.05). We suggest that the gastric milieu for H pylori is less appropriate in type III intestinal metaplasia positive patients. As type III intestinal metaplasia might be regarded as a marker of possibly increased gastric cancer risk, the lower prevalence of H pylori in these type III intestinal metaplasia positive patients might be the result of severe changes in mucosal architecture. PMID- 1612474 TI - Suppression of Helicobacter pylori reduces gastrin releasing peptide stimulated gastrin release in duodenal ulcer patients. AB - Helicobacter pylori increases gastrin release in duodenal ulcer patients. This may be through disruption or changes in the mucus layer affecting the access of luminal stimulants to gastrin releasing cells. The effect of suppressing H pylori on gastrin release stimulated by a non-luminal stimulus, gastrin releasing peptide (GRP), was examined. Eleven patients with active duodenal ulcer disease and colonised with H pylori received an intravenous infusion of GRP (2.9 pmol/kg/minute for 30 minutes) and the plasma gastrin response was measured. Basal and peak pentagastrin stimulated acid output were also determined. Patients were treated with tripotassium dicitratobismuthate (De-Nol) and metronidazole to suppress H pylori and the tests were repeated. Suppression of H pylori decreased plasma gastrin concentrations during GRP infusion, but acid output was not affected. Chromatographic analysis of the forms of gastrin in plasma showed a significant fall in gastrin 17, the predominant form found in the gastric antrum. Gastrin 34 did not fall significantly. This study shows that suppression of H pylori decreases the hypergastrinaemia caused by the nonluminal stimulant, GRP, mainly via decreasing gastrin 17. PMID- 1612475 TI - Ecology of Helicobacter pylori in Peru: infection rates in coastal, high altitude, and jungle communities. The Gastrointestinal Physiology Working Group of the Cayetano Heredia and the Johns Hopkins University. AB - We have examined endoscopic clinic patients in three widely different geographic regions of Peru (the coast, the Sierra of the Andes Mountains, and the Amazon jungle) for the presence of Helicobacter pylori infection associated with active gastritis. The overall rates of infection were high (80% or greater) in all three zones and rates for men were approximately 10% higher than for women in the same zone. Men and women in the Sierra and jungle areas had significantly higher rates of infection than did those on the coast. There was no significant difference between the three populations with respect to the relationship between infection and grade of gastritis. PMID- 1612476 TI - Assessment of the percutaneous endoscopic gastrostomy feeding tube as part of an integrated approach to enteral feeding. AB - The insertion of percutaneous endoscopic gastrostomy has been well documented. The possible benefits for patient nutrition and nursing practice have, however, not been assessed. We report a study of enteral feeding by percutaneous endoscopic gastrostomy in 30 patients, the majority with a persistent vegetative state. All patients had previously been fed through a nasogastric tube using manual administration and a dietitian assessed protein calorie intake. Based upon body mass index (weight/height2), midarm circumference and triceps skinfold thickness, 20 (67%) were malnourished, with 10 patients having a body mass index less than 17 (severe malnutrition); attributed to high rates of both tube displacement and feed regurgitation. Patients were observed over six to 12 months after percutaneous endoscopic gastrostomy insertion combined with overnight continuous pump feeding. All patients attained a body mass index greater than 17, and 17 (56%) of the total number achieved the normal range with no change in protein-calorie intake (pre: 2110 kcal, post: 1880 kcal). Complications of percutaneous endoscopic gastrostomy in the study group included peritonitis (one), tube site infection (two) and displacement (two); all without serious sequelae. As part of an integrated approach percutaneous endoscopic gastrostomy proved a safe and efficient method of enteral feeding and justifies wider consideration in the United Kingdom. PMID- 1612477 TI - Immunoreactivity of transforming growth factor alpha in the normal adult gastrointestinal tract. AB - The immunolocalisation of transforming growth factor alpha (TGF alpha) in the normal human oesophagus and the gastrointestinal tract was elucidated using two different antibodies - Ab2, a monoclonal antibody reacting with part of the human TGF alpha molecule, and 26T a rabbit affinity purified polyclonal antibody raised against part of the rat TGF alpha peptide. There have been conflicting reports on the distribution of this growth factor in the gut. The results clearly showed that this peptide regulatory factor is confined to the luminal surface and foveolae in the stomach, restricted to the villous epithelium in the small intestine, and in the colon was seen in the upper one third of the crypt. This pattern indicates that the distribution of this peptide regulatory factor is within the differentiated compartment and indicates a role in differentiation besides its well known proliferative effects. PMID- 1612479 TI - Preponderance of IgM from blood lymphocytes in response to infantile rotavirus gastroenteritis. AB - Immune responses triggered by acute rotavirus infection in infants are poorly defined. To obtain indirect evidence as to gut immune response to rotavirus, the solid phase enzyme linked immunoassay (ELISPOT) of immunoglobulin and specific antibody secreting cells among circulating blood lymphocytes was used. Seventeen well nourished patients from seven to 25 months of age were studied during the peak of rotavirus infection, and in convalescence. A transient but distinct immunoglobulin secreting cell response in IgM and IgG, but not in IgA, classes was found during the diarrhoeal phase. This response included a quantitatively prominent activation of specific antibody secreting cells against rotavirus in the IgM class, mean (95% confidence interval (CI)) 82 (32, 210)/10(6) cells v 8 (4, 17)/10(6) cells in convalescence, p = 0.01. The response in the IgA class was not significant. The results indicate that local immune mechanisms are activated in rotavirus diarrhoea. They further suggest that although IgA is the predominant immunoglobulin operative in the gastrointestinal tract, this may not be the case in infantile rotavirus enteritis. PMID- 1612478 TI - Serum IgG subclass antibodies to a variety of food antigens in patients with coeliac disease. AB - Levels of serum IgA, IgG, and IgG subclass antibodies to a variety of dietary antigens were determined by enzyme linked immunosorbent assays in 14 adults with untreated coeliac disease and in 10 disease controls selected because of raised total IgG activities. The untreated coeliacs showed somewhat higher total IgG activity (p approximately 0.05) and significantly raised IgA and IgG1 + IgG3 activities to gliadin but reduced IgG4 activity (p less than 0.02) compared with the controls. High IgA and IgG1 + IgG3 activities were positively correlated (r = 0.67, p less than 0.01), and so were IgG and IgG4 activities (r = 0.64, p less than 0.02). Conversely, a high IgG2 response to gliadin appeared related to a low IgA response (r = 0.55, p less than 0.05). The IgG2 response was most prominent to oat flour antigens, followed by IgG1; and the main response to soy antigens resided in IgG1, followed by IgG2 in both disease groups. There was no difference in antibody activities to oat and soy between the two groups, and raised activity to bovine serum albumin was seldom encountered. The IgA activity to alpha lactalbumin and ovalbumin tended to be increased in the coeliacs compared with the controls. The IgG4 subclass dominated the IgG response to beta-lactoglobulin and ovalbumin and was often raised to alpha-lactalbumin, especially in the disease controls. The IgG subclass pattern to casein parallelled that to gliadin with dominance of the IgG1- and IgG3-subclass activities, especially in the coeliacs. The phlogistic potential of a response in these two subclasses might be relevant to the pathogenesis of coeliac disease and could contribute to a raised IgA gliadin response by increasing mucosal permeability. IgA activity seemed to be highest against antigens usually involved in IgE mediated food allergy. PMID- 1612480 TI - Indomethacin decreases jejunal fluid secretion in addition to luminal release of prostaglandin E2 in patients with acute cholera. AB - Human cholera is associated with an increased luminal release of prostaglandin E2 (PGE2), but whether inhibition of increased PGE2 synthesis will reduce or control intestinal secretion is uncertain. 'Steady state' perfusions (10 ml/minute) in 12 patients with acute cholera, and repeat perfusions in nine of these patients during the convalescent phase were therefore performed using the triple lumen technique. The proximal jejunum was perfused with isotonic saline containing sodium-sulphobromophthalein as a non-absorbable marker. After intravenous administration of indomethacin (1.0 mg/kg) the jejunal net transfer of fluid and the jejunal flow rate of PGE2 were determined in 30 minute periods for 120 minutes after a 120 minute control period. Indomethacin decreased net fluid secretion (2.1 (0.3-4.2) v 4.5 (2.5-8.4) ml/hour x cm; medians, Q50 ranges, p less than 0.01) and the jejunal flow rate of PGE2 (1.5 (1.2-2.7) v 2.2 (1.4-4.9) ng/minute, p less than 0.05). The results of similar perfusion studies in 22 patients with acute cholera, used to establish the spontaneous time related change in fluid secretion, showed no significant change in net fluid transfer (3.5 (2.2-6.2) to 3.5 (2.6-11.6) ml/hour x cm, p greater than 0.25) over 240 minutes. These data provide further evidence in favour of the hypothesis that prostaglandins have a role in the cholera toxin induced intestinal fluid secretion in man. PMID- 1612481 TI - Virulence properties of Escherichia coli strains isolated from patients with inflammatory bowel disease. AB - Escherichia coli strains cultured from 74 patients with inflammatory bowel disease at different stages of disease activity (Crohn's disease (40), ulcerative colitis (34)) and 18 healthy controls were studied in relation to haemolysin and verotoxin production and enteroadherence. Disease activity was assessed by standard clinical and laboratory tests. Haemolytic E coli were isolated from 18% of patients with Crohn's disease, 24% with ulcerative colitis, and 11% of healthy controls. None of these differences was significant. No verotoxin producing strains were detected among the 216 E coli isolates examined but the extract from five strains (Crohn's (4), ulcerative colitis (1) produced a distinctive cytopathic effort on Vero cell monolayers which was later shown not to be due to verotoxin. The adhesion indices of E coli isolates cultured were: mean (SEM) 42.2 (6.4) for Crohn's disease, 43.3 (6.2) for ulcerative colitis, and 11.3 (2.0) for normal controls (p less than or equal to 0.0001). Adhesive E coli were isolated from 62% of patients with Crohn's disease and 68% with ulcerative colitis but from only 6% of normal controls (p less than or equal to 0.0002). Neither haemolysin production nor enteroadherence was dependent upon disease activity, disease location, sulphasalazine treatment, or previous intestinal resection. These results indicate that only enteroadherent E coli were frequently associated with inflammatory bowel disease; their relation to the pathogenesis of these conditions, however, remains uncertain. PMID- 1612482 TI - Increased expression of c-myc proto-oncogene in biopsies of ulcerative colitis and Crohn's colitis. AB - The steady state levels of c-myc mRNA have been measured in RNA samples extracted from colonoscopic biopsies of inflammatory bowel disease patients obtained at routine endoscopy sessions. Biopsies were immediately frozen in liquid nitrogen limiting the ischaemic time to less than 15 seconds, and can be stored for up to 96 hours before separation of RNA. Yields of RNA using biopsies were 0.137 (0.041)% wet wt (mean (SD), n = 68), these are significantly better than those obtained from surgical material (0.064 (0.063)% wet wt (mean (SD), n = 21) where the tissue ischaemic time was 45 minutes to one hour 40 minutes. Functional activity of RNA extracted was demonstrated by the ability to direct in vitro protein translation in the rabbit reticulocyte system. We have used this technique to show that there is an increased ratio of steady state c-myc proto oncogene expression in inflamed tissue from 18 patients with left sided ulcerative colitis and five patients with segmental Crohn's colitis, compared with an uninvolved region of the colon in each case. No difference in c-myc expression was seen in biopsies at least 30 cm apart in 11 control patients with no macroscopic or histological abnormalities. Increased expression of c-myc in inflammatory bowel disease is consistent with the activation of this proto oncogene during altered cell cycle control resulting from the inflammatory process. PMID- 1612483 TI - Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis. AB - The presence of perinuclear antibodies against neutrophils (pANCA) has been detected recently in sera of patients with inflammatory bowel disease and primary sclerosing cholangitis. In order to evaluate their clinical significance, sera from 126 patients with inflammatory bowel disease (80 Crohn's disease and 46 ulcerative colitis and 22 patients with primary sclerosing cholangitis were examined for pANCA by indirect immunofluorescence on liver sections and cytocentrifuge slides of neutrophils and by immunoblot. Perinuclear antibodies against neutrophils were found in 83% of patients with ulcerative colitis in 88% of patients with primary sclerosing cholangitis and inflammatory bowel disease, in 40% of patients with primary sclerosing cholangitis but without inflammatory bowel disease, and in 25% of patients with Crohn's disease using the immunofluorescence test. Titres of pANCA ranged from 1:10 to 1:1000 in ulcerative colitis and primary sclerosing cholangitis (median 1:100), whereas in Crohn's disease only four patients had titres of more than 1:10. The occurrence of pANCA did not correlate with clinical activity of Crohn's disease and primary sclerosing cholangitis whereas in ulcerative colitis high titres of pANCA were found mainly in active disease. Using an immunoblot system with sonified neutrophils as antigen, 82% of sera from patients with primary sclerosing cholangitis reacted with up to five different determinants, whereas only 12% of sera from patients with Crohn's disease and 11% of sera with ulcerative colitis detected one of the determinants, suggesting different antigens involved in pANCA reaction. PMID- 1612484 TI - DNA aneuploidy in Crohn's disease and ulcerative colitis: results of a comparative flow cytometric study. AB - DNA ploidy and S-phase fractions were assessed by flow cytometry in colonic biopsy specimens from 28 patients with ulcerative colitis and 51 with Crohn's disease. Whereas only diploid DNA histograms were found in Crohn's disease and control subjects, three patients with ulcerative colitis exhibited DNA aneuploidy. In one case, aneuploidy was associated with low grade dysplasia. S phase fractions were higher in ulcerative colitis (mean (SD) 17.8 (7.7)%) than in Crohn's disease (13.1 (4.6)%) or control subjects (14.2 (4.6)%), but did not correlate with either disease activity or duration in any group. In this study, aneuploidy was associated exclusively with ulcerative colitis, even in the absence of dysplasia. In view of the epidemiological differences in malignant colonic transformation between ulcerative colitis and Crohn's disease, this study suggests that flow cytometry may help to identify individuals with an increased cancer risk in ulcerative colitis. PMID- 1612485 TI - Anti-neutrophil antibodies in inflammatory bowel disease: prevalence and diagnostic role. AB - Anti-neutrophil antibodies have been shown in sera from patients with a variety of inflammatory diseases. Those reacting with components of neutrophil cytoplasm are associated with systemic vasculitis. Both nuclear and perinuclear staining patterns on human neutrophils have been reported using sera from patients with inflammatory bowel disease. We have evaluated the reactivity against human neutrophils of sera from 100 patients with inflammatory bowel disease, 14 disease controls, and 20 normal volunteers. Altogether 27/50 (54%) sera from patients with ulcerative colitis contained antibodies that reacted with cytospun ethanol fixed neutrophils compared with 5/50 (10%) from Crohn's disease (p less than 0.001) and 0/34 control sera (p less than 0.001). All seven sera from patients with proctitis alone were negative (p less than 0.01). There was no correlation between presence or titre of anti-neutrophil antibodies and either disease activity or treatment. Positive sera gave three different staining patterns on human neutrophils. The predominant pattern was perinuclear (17/32); 12 sera gave a cytoplasmic and three a homogeneous nuclear staining pattern. None of the patients or the controls had antibodies to myeloperoxidase, elastase, or serine proteinase 3, all of which are recognised by anti-neutrophil cytoplasmic antibodies. Only 2/27 sera positive by indirect immunofluorescence reacted with an extract of neutrophil primary granules. In conclusion, anti-neutrophil antibodies occur more commonly in ulcerative colitis than in Crohn's disease or control subjects and the anti-neutrophil antibodies found in inflammatory bowel disease are different from those associated with vasculitis. PMID- 1612486 TI - Whole body protein turnover in childhood Crohn's disease. AB - In order to investigate the effects of treatment on protein metabolism in childhood Crohn's disease whole body protein turnover was measured using a primed constant intravenous infusion of L-[1-13C]leucine and mass spectrometry in 10 children with active disease. Mean rates of protein synthesis and breakdown markedly decreased after treatment with steroids (four) or an elemental diet (six). This suggests that protein synthesis and breakdown are increased during active Crohn's disease in children and are reduced after induction of remission regardless of the type of treatment. PMID- 1612487 TI - Increased pulmonary and intestinal permeability in Crohn's disease. AB - We tested the hypothesis that an increased epithelial permeability may affect sites other than the intestine in patients with Crohn's disease by simultaneously evaluating their pulmonary and intestinal permeability. Pulmonary and intestinal permeability were measured by clearance of inhaled technetium-99m diethylene triamine pentacetate (99mTc-DTPA) and by urinary recovery of chromium-51 ethylene diamine tetracetate respectively in 22 patients with Crohn's disease. The half time clearance of 99mTc-DTPA from lung to blood (t1/2LB) was decreased--that is pulmonary permeability increased--in the whole group of patients with Crohn's disease as compared with 13 controls (median 45.5 minutes (8-160) v 85 minutes (34-130) (p less than 0.003)). When analysed separately only patients with active Crohn's disease (n = 15) had a decreased t1/2 lung to blood v controls (42 minutes (8-160) v 85 minutes (34-130) (p less than 0.0025)). Among patients with active Crohn's disease, six were studied again when their disease was quiescent and their t1/2 lung to blood did not differ significantly. The intestinal permeability was increased in the whole group of Crohn's disease patients as compared with 15 controls (5.25% (1.2-24) v 1.7% (0.65-5.75) (p less than 0.0002)). When analysed separately both patients with active and inactive Crohn's disease had increased intestinal permeability v controls (8.1% (1.6-24) and 3.5% (1.2.9.2) v 1.7% (0.65-5.75)) (p less than 0.0001, p = 0.05 respectively). Six patients with active Crohn's disease were studied again when their disease was quiescent and their intestinal permeability decreased significantly p less than 0.04). Pulmonary permeability was increased in patients with Crohn's disease but was not greatly influenced by Crohn's disease activity as opposed to intestinal permeability. The mechanism of this increase is unknown, but may be related in some patients to the presence of an alveolitis. PMID- 1612488 TI - Non-steroidal anti-inflammatory drugs as a possible cause of collagenous colitis: a case-control study. AB - The use of oral non-steroidal anti-inflammatory drugs (NSAIDs) in 31 patients with collagenous colitis and in 31 matched control patients with irritable bowel syndrome or colonic diverticular disease who had also undergone colonoscopy and biopsy was investigated. The long term use (greater than 6 months) of NSAIDs was significantly commoner in the study group (19/31) than in the control group (4/31) (p less than 0.02), even assuming the most adverse drug history in six patients in whom this could not be established. In all patients with collagenous colitis taking NSAIDs, diarrhoea followed the use of these drugs, and by a mean (SD) of 5.5 (4.4) years (range 0.5 to 15 years). In three patients with collagenous colitis, diarrhoea improved after withdrawing NSAIDs; rechallenge in one was followed by a recurrence of diarrhoea, which improved after withdrawing the drug again. It is suggested that NSAIDs may play an aetiological role in the diarrhoea and thickened collagen band in some patients with collagenous colitis. PMID- 1612489 TI - Tumour necrosis factor alpha secretion in leporine endotoxaemia: role of the liver and effects of hepatic ischaemia. AB - A leporine model to investigate tumour necrosis factor alpha (TNF alpha) secretion after peripheral vein or mesenteric vein lipopolysaccharide injection was devised. Mesenteric vein injection provoked lower arterial concentrations after 90 minutes (median (range), 2.81, (0.75-11.96) ng/ml) than peripheral vein injection (7.00 (4.27-14.95) ng/ml (p less than 0.05)). Mesenteric vein injection after 10 minutes' warm hepatic ischaemia, which impairs hepatic clearance, provoked higher median arterial TNF alpha values at 90 minutes (7.98 (2.85-21.48) ng/ml) than in normal animals (p less than 0.05). Portal vein endotoxaemia induced less TNF alpha production than systemic endotoxaemia unless hepatic clearance was impaired, thus the major source of TNF alpha in systemic endotoxaemia is probably extrahepatic. PMID- 1612490 TI - Computed tomography in predicting gall stone solubility: a prospective trial. AB - This prospective study was undertaken to evaluate the correlation between densitometric values of gall stones assessed by computed tomography and the success rate of litholytic therapy in 28 patients eligible for oral treatment. A densitometric study of the stones was performed in all patients before treatment. A cut off point of 60 Hounsfield units (HU) was chosen to divide the subjects into two groups--group 1, 14 patients with low density stones (less than 60 HU) and group 2, 14 patients with high density stones (greater than 60 HU). All patients were treated with ursodeoxycholic acid (8-10 mg/kg/day) for 12 months and followed up by ultrasound. In group 1, dissolution was complete in 50% of the patients and partial in a further 20%. In group 2 patients, complete dissolution was not observed but 33% showed partial dissolution. The number of patients with total dissolution at 12 months was significantly higher in group 1 compared with group 2 (p less than 0.02). These results suggest that computed tomography can be used to select patients with a better likelihood of successful stone dissolution after bile acid therapy. PMID- 1612492 TI - Oral fluticasone propionate in active distal ulcerative colitis. AB - Fluticasone propionate is a new corticosteroid with low systemic bioavailability. This study reports the outcome of a double blind clinical trial comparing oral fluticasone propionate (5 mg four times daily) with placebo for the treatment of active distal ulcerative colitis. Sixty patients were treated for four weeks, with assessments at two and four weeks. One patient was withdrawn when she was found to have amoebiasis. Thus, results are presented for 29 patients who received placebo and 30 who received fluticasone propionate. The two groups were well matched for age, sex, length of history, and extent of disease. After four weeks of therapy the clinical, sigmoidoscopic, and histological responses were similar in the two groups. It is concluded that fluticasone propionate (5 mg four times daily) is not effective treatment for active distal ulcerative colitis. PMID- 1612491 TI - Vitamin A absorption in cystic fibrosis: risk of hypervitaminosis A. AB - Vitamin A status was examined in nine adult cystic fibrosis patients and six adult control subjects, together with an assessment of their ability to absorb 10,000 IU of retinyl palmitate from a test meal, taken with appropriate pancreatic enzyme supplements. Median baseline values for plasma retinol and carotene, as well as median serum retinol binding protein concentrations, were significantly lower in cystic fibrosis patients than in control subjects. One cystic fibrosis patient had a raised fasting plasma retinyl ester concentration suggestive of chronic hypervitaminosis A, but no symptoms of toxicity. Measures of vitamin A absorption were also significantly lower in cystic fibrosis patients, although there was considerable overlap with control values. No correlation was observed between measures of baseline status and vitamin A absorption. Measurement of plasma retinyl esters may be an appropriate investigation in those patients considered to be at risk of chronic hypervitaminosis A. PMID- 1612493 TI - Gastric antral vascular ectasia: maintenance treatment with oestrogen progesterone. AB - Gastric antral vascular ectasia ('watermelon stomach') is a rare cause of chronic gastrointestinal bleeding and various medical and surgical treatments have been described. We report a patient in whom an oestrogen-progesterone preparation successfully controlled recurrent blood loss. PMID- 1612494 TI - Relation between electromyography and anal manometry of the external anal sphincter. PMID- 1612495 TI - Septicaemia after colonoscopy in patients with cirrhosis. PMID- 1612496 TI - Endometrial carcinoma: the need to pursue a new path(ology) PMID- 1612497 TI - Identification of patients with stage I uterine endometrioid adenocarcinoma at high risk of recurrence by DNA ploidy, myometrial invasion, and vascular invasion. AB - The presence of vascular invasion-associated changes (VIAC), which include vascular invasion by tumor and/or the presence of myometrial perivascular lymphocytic infiltrates, has been previously described as a key prognostic indicator in patients with stage I endometrioid (typical) adenocarcinoma of the uterus. In the current report, the prognostic significance of DNA ploidy in addition to other clinical and pathologic features including VIAC was determined in 57 previously examined stage I endometrioid adenocarcinomas of the uterine corpus. By univariate analysis, age at the time of diagnosis, architectural and nuclear tumor grades, DNA ploidy, depth of myometrial invasion, and the presence of VIAC all correlated with clinical outcome. By multivariate survival analysis, only the depth of myometrial invasion, DNA ploidy, and VIAC were found to significantly correlate with survival. A statistical model based on these three features permits stratification of patients into four risk groups with 93, 67, 38, and 10% survival, respectively. PMID- 1612498 TI - Cryosurgery for cervical intraepithelial neoplasia: 10-year follow-up. AB - Cryotherapy was performed for the treatment of CIN in 261 patients, who were followed for 5 to 10 years after treatment. The overall cure rate was 83.5%. Increasing grade of CIN and enocervical involvement significantly reduced the cure rate. In pure exocervical lesions, a 91% cure rate in patients with CIN II lesions and a 77.8% cure rate in CIN III patients were observed. In patients with endocervical involvement, the influence of grade of lesion was of no significance. Life-table calculations demonstrated an overall risk of persisting CIN during the first year of observation of 8.8%, compared to a risk of 0.8% during Years 6 to 10. Log-rank test showed a risk of recurrence in patients with CIN III lesions significantly higher than that in patients with CIN II lesions and also a higher risk in patients with endocervical involvement. There was no significant influence of age on cure rates. Endocervical involvement should be considered a contraindication to cryotherapy, and a careful follow-up schedule is mandatory if cryotherapy is to keep its position as a recommendable therapy in patients with CIN. PMID- 1612499 TI - Complications in the use of intra-abdominal 32P for ovarian carcinoma. AB - From 1982 through 1989, 94 patients at the University of Louisville with ovarian neoplasm had abdominal instillation of 15 mCi chromic 32P as part of their management. The timing of the 32P was immediately postoperative in 55 patients and delayed greater than 24 hr in 39 patients. This is an analysis of factors contributing to gastrointestinal (GI) complications. GI complications were graded according to RTOG guidelines. There was a total of 11 GI complications grade 3 or worse for an overall incidence of 12%. Factors analyzed include timing of 32P delivery, age, stage, number of previous surgeries, use of Hyskon at surgery, addition of external beam radiation, and subsequent use of chemotherapy. There were significantly fewer complications when 32P was given on the same day as surgery than when 32P administration was delayed more than 12 hr following surgery (4% vs 21%), P = 0.007. This difference held significance when adjusted for the number of previous surgeries, use of Hyskon, external beam radiation, and stage. None of the other factors had a significant effect on complication rate. There have been no incidences of contamination even though 32P instillation in the immediate post-operative period had increased risk of contamination due to wound leakage or reoperation. In our experience, the delivery of 32P in the immediate postoperative period resulted in a significant reduction in abdominal complications. PMID- 1612500 TI - Management of vulvar melanoma. AB - Considerable debate centers on the optimal treatment for vulvar melanoma, as well as those clinicopathological factors influencing prognosis. We reviewed 80 patients with vulvar melanoma seen between 1949 and 1990. Primary tumors were assessed according to Chung (47 patients) and Breslow (65 patients) microstaging systems. Fifty-nine patients (76%) underwent radical vulvectomy, ten patients (13%) had a partial vulvectomy, and nine patients (12%) had a wide local excision. Fifty-six also underwent inguinal node dissection. Median follow-up was 193 months. Median survival was 63 months. Ten-year survival by Chung level was as follows: I 100%; II, 81%; III, 87%; IV, 11%; V, 33%. Ten-year survival by tumor thickness was as follows: 0.75 mm, 48%; 0.75-1.5 mm, 68%; 1.51-3.0 mm, 44%; greater than 3.0 mm, 22%. Increased depth of invasion was associated with increased incidence of inguinal node metastasis. Cox regression analysis demonstrated prognostic significance for tumor thickness (P less than 0.001), inguinal node metastasis (P less than 0.001), and older age at diagnosis (P less than 0.001). Radical vulvectomy did not seem to improve survival over less radical procedures. Based on this experience, we recommend radical local excision for patients with malignant melanoma of the vulva. Patients who have more than a superficially invasive melanoma should also have inguinal lymph node dissection. PMID- 1612501 TI - Ovarian tumors of low malignant potential: transvaginal Doppler ultrasound features. AB - Twenty-nine patients with ovarian tumors were studied with transvaginal Doppler ultrasound before surgery. After surgery, pathological examination revealed that 26 tumors were benign and 3 were of low malignant potential (LMP). B-mode sonography, computed tomography, and magnetic resonance imaging showed no positive findings for malignancy in these 3 cases of LMP. Serum levels of the CA 125, tissue polypeptide antigen, and carcinoembryonic antigen were also within the normal range. Blood flow velocity waveforms were evaluated by the calculation of the resistance index (RI). There was a significant difference between the RI value (0.818 +/- 0.223) in benign tumors and that (0.418 +/- 0.072) in LMP (P less than 0.01). When the 0.56 (mean of LMP tumor RI value + 2SD) was considered as the cutoff value of RI, the sensitivity was 100% and the specificity was 88.5%. Transvaginal Doppler ultrasound provides a useful diagnostic information for the differentiation of benign and LMP ovarian tumors before surgery. PMID- 1612503 TI - Characterization of a human endometrial carcinoma cell line producing intraperitoneal tumor growth in immunodeficient mice. AB - Establishment of laboratory models of gynecologic neoplasms provides an important means of studying the biologic characteristics of these tumors. We report a previously uncharacterized human endometrial adenocarcinoma cell line that produces both intraperitoneal and subcutaneous growth in nude mice. The line was derived from a poorly differentiated endometrial cancer and has been carried in continuous tissue culture for greater than 100 passages. Doubling time in culture is approximately 48 hr. Antigenic phenotyping against a panel of murine monoclonal antibodies by rosetting cell surface assay on live cells or peroxidase assay on fixed cells has shown reactivity with a number of determinants, including MH99, MT334, MQ49, and the blood group antigens F3, 118, and 41-83. Cytogenetically, the line displays an aneuploid human karyotype with several chromosomal rearrangements and deletions. When injected intraperitoneally into nude mice, animals develop intraperitoneal nodules and ascites and succumb with wasting in 30-40 days. The intraperitoneal tumor has been passaged multiple times in nude mice by direct transfer of ascites. Subcutaneous injection of tumor cells produces nodules that grow at a reproducible rate. By light and electron microscopy, the nude mouse tumor is a poorly differentiated adenocarcinoma, similar to the original patient's tumor. It expresses both estrogen and progesterone receptors. CA 125 is not elevated in the serum of animals with tumor implants. The line appears to be cisplatin sensitive as determined by rates of growth of subcutaneous nodules. This cell line may be useful in studying the in vitro and in vivo properties of human endometrial carcinoma. PMID- 1612502 TI - Intraperitoneal radioimmunotherapy of refractory ovarian carcinoma utilizing iodine-131-labeled monoclonal antibody OC125. AB - Refractory epithelial ovarian cancer is generally confined to the peritoneal cavity and is thus amenable to intraperitoneal (ip) therapy. Radiolabeled monoclonal antibodies raised to tumor-associated antigens offer the promise of selective tumor irradiation while reducing toxicity to normal tissues. We have conducted a phase I therapeutic trial to examine the feasibility of ip radioimmunotherapy utilizing escalating doses of 131I-labeled OC125 F(ab')2. Twenty-nine patients were each treated with a single dose of radiolabeled antibody. Twenty-eight patients were evaluable for dose-related toxicity. The toxicities most frequently observed were hematologic and gastrointestinal. Hematologic toxicity was noted in 5/14 (36%) patients receiving 18-87 mCi and in 12/14 (71%) receiving 100-144 mCi (P = 0.018). The median white blood cell nadir of 2-3K/microliters (range, 1.4-3.5K/microliters occurred at a median of 4.5 weeks and the median platelet nadir of 41K/microliters (range, 20 78K/microliters) at a median of 6.5 weeks. Mild gastrointestinal toxicity was observed in 4/14 patients (28%) at doses less than 100 mCi whereas at doses greater than or equal to 100 mCi, 11/14 (79%) patients developed nausea, vomiting, or chronic ileus (P = 0.021). This toxicity occurred most frequently in patients with protracted urinary 131I excretion. We conclude that 131I-labeled OC125 can be safely administered ip. Hematologic and gastrointestinal toxicity is predictable and related to the dose and rate of clearance of isotope. PMID- 1612504 TI - Tumor markers of epithelial and stromal cell origin at second-look laparotomy in ovarian carcinoma. AB - The accuracy of CA 125, amino-terminal propeptide of type III procollagen (PIIINP), and clinical examination were evaluated in association with 48 second look laparotomies of ovarian carcinoma patients treated with cytotoxic chemotherapy. At laparotomy, there were 23 macroscopical and 6 microscopical tumors. Nineteen patients were disease-free. Clinical examination, CA 125, and PIIINP were correctly positive in 93, 92, and 82% of cases, respectively. When CA 125 and PIIINP were used simultaneously this value increased to 100%. The sensitivity of CA 125 (43%) and PIIINP (56%) was unsatisfactory, but with their combination it increased to 62%. The use of CA 125, PIIINP, or both increased the sensitivity of clinical examination by 14, 24, and 27%, respectively. Of all the occult tumors, CA 125 detected 33%, PIIINP 57%, and both 66%. The detection rate of macroscopical tumors missed at clinical examination by both was 71%. Hence, PIIINP may be a clinically valuable complement to CA 125 and clinical examination before second-look laparotomy. PMID- 1612505 TI - Randomized prospective trial of 5 versus 10 cycles of cyclophosphamide, doxorubicin, and cisplatin in advanced ovarian carcinoma. AB - Five versus ten cycles of cyclophosphamide, doxorubicin, and cisplatin (CAP) were compared in advanced ovarian carcinoma by a prospective randomized study of 78 patients, 41 receiving 5 cycles (CAP5) and 37 receiving 10 cycles (CAP10) of chemotherapy. Patients were stratified by histologic grade and size of residual disease. Cyclophosphamide, 600 mg/m2, doxorubicin, 40 mg/m2, and cisplatin, 100 mg/m2, were administered every 4 weeks for 5 or 10 cycles. Second-look laparotomy was performed to evaluate response and plan further therapy. CAP5 patients found a second-look laparotomy to have partially responded to chemotherapy were treated with 5 additional cycles of CAP. CAP10 was more toxic than CAP5 with respect to myelosuppression, hospital admissions for nadir fever, median elevation of creatinine, and degree of peripheral neuropathy. Median follow-up is 64 months. CAP5 and CAP10 were equivalent in surgically documented complete responses (34 versus 35%) and survival (P = 0.41). Twelve partial responders to CAP5 received additional CAP chemotherapy; one complete response resulted. We conclude that CAP5 is preferable to CAP10 in treatment of advanced ovarian cancer as it is equally effective and less toxic. PMID- 1612506 TI - The Gore-Tex Surgical Membrane: effectiveness as a barrier to inhibit postradical pelvic surgery adhesions in a porcine model. AB - Radical pelvic surgery has well-defined side effects, many of which may be related to the formation of pelvic adhesions. The effectiveness of different agents at limiting the formation of postradical pelvic surgery adhesions (PRPSA) has been variable to date. Use of a barrier could be beneficial not only by limiting adhesion formation but by acting as a "pelvic lid" to elevate the bowel out of a radiation treatment field and therefore limit subsequent radiation injury and associated fistula formation. We investigated the ability of the Gore Tex Surgical Membrane (Gore-SM) to inhibit PRPSA in 20 adult female hogs undergoing radical hysterectomy, bilateral salpingo-oophorectomy, and resection of pelvic peritoneum. After completion of the radical resection, animals were randomized to either no attempt at covering the peritoneal defect or covering it and a 1-cm margin of intact peritoneum with a tailored sheet of Gore-SM. The membrane was secured in place using a continuous running 4-O Prolene suture around the perimeter. No intraoperative deaths occurred. No animal evidenced signs of bleeding, infection, bowel obstruction, or abscess formation. Four weeks after the initial surgery, the animals were again anesthetized, exploratory celiotomy was performed, and adhesions were quantified with specific note being made of any segments of small bowel that were adherent into the pelvis. Animals were then sacrificed. Adhesion scores for the Gore-SM-treated animals (n = 10; mean, 0.14 +/- 0.12; median, 0.21) were significantly less than those of animals with the noncovered pelvis (n = 10; mean, 1.33 +/- 0.41; median, 1.42; P less than 0.001). Similarly, significantly fewer animals treated with Gore-SM had small bowel loops adherent in the pelvis when compared to control animals (10% vs 70%; P less than 0.01). In this model, meticulously suturing the membrane in place with continuous permanent suture, the Gore-SM was an effective barrier for postoperative adhesion prophylaxis and successfully limited small bowel adherence into the pelvis. PMID- 1612508 TI - Superficially invasive squamous cell carcinoma of the cervix. AB - The microscopic pathologic features of early invasive squamous cell cervical carcinoma are used as determinants for the treatment of these lesions. This study is a retrospective review of 180 patients with squamous cell cervical carcinoma with invasion to a depth of 5 mm or less. Invasion of less than or equal to 1 mm, greater than 1 but less than or equal to 3 mm, greater than 3 but less than or equal to 5 mm was noted in 37, 84, and 59 patients, respectively. The median follow-up was 6.5 years. Four (2.2%) patients developed carcinoma in situ of the vagina and four (2.2%) patients progressed to invasive squamous carcinoma. Pelvic lymph node metastases were rare (1%). No patient has died from recurrent disease. Analysis of numerous clinical and pathological variables identified no risk factors for recurrence. Most (54/68) patients with tumor invading beyond 3 mm or with tumor demonstrating vascular invasion were treated by traditional "radical" methods. This limited a meaningful analysis of the risk of conservative treatment. The reliability of using the existing definitions of microinvasive disease for the guidance of treatment remains controversial. Further clarification may be rendered only with prospective clinical-pathologic studies performed by cooperative groups. PMID- 1612507 TI - Management of endometrial adenocarcinoma with cervical involvement. AB - Seventy-seven patients with endometrial cancer with cervical involvement were treated at Memorial Sloan-Kettering Cancer Center from 1968 to 1982. Fractional curettage specimens showed that 25 patients (32%) had involvement of cervical stroma and 52 (68%) had only detached fragments of carcinoma present in endocervical curettings. Six patients treated for palliation only are excluded from analysis of treatment and survival. Our preferred treatment during the time interval studied consisted of preoperative whole pelvic radiotherapy followed by modified radical hysterectomy and bilateral salpingo-oophorectomy with post operative intravaginal brachytherapy. This regimen was well tolerated by the 37 patients so treated. The remaining patients were treated with a variety of regimens, most commonly radiotherapy and simple hysterectomy (25 patients). With a mean follow-up among survivors of 97 months, disease-free survival is 72%. Mean time to relapse was 19 months, with 90% of relapses occurring within 40 months. Initial sites of relapse included abdomen, 9 (12.6%); lungs, 8 (11.3%); brain, 2 (2.8%); lateral pelvis, 2 (2.8%); and bone, 1 (1.4%). Clinicopathologic variables significantly related to risk of relapse included presence of extrauterine disease at surgery (P = 0.0001), extent of cervical involvement as determined prior to hysterectomy (P = 0.001), depth of myometrial invasion (P = 0.005), and papillary serous histology (P = 0.0002). Treatment of endometrial cancer with cervical involvement with combinations of radiotherapy and surgery is well tolerated and results in an excellent long-term disease-free survival and a low rate of pelvic relapse. PMID- 1612509 TI - Prognostic value of pathological patterns of lymph node positivity in squamous cell carcinoma of the vulva stage III and IVA FIGO. AB - Lymph node positivity in invasive squamous cell vulvar cancer implies a severe decrease in survival rates. Pathological lymph node positivity covers a wide range of metastatization patterns. In the present investigation the nodal positivity of 53 patients affected by Stage III and IVA invasive vulvar squamous cell carcinoma has been carefully evaluated and correlated with survival. Number, size of the metastasis inside the node, intracapsular or extracapsular site of the metastasis, and immune response of the positive nodes were considered. Cancer related survival has been obtained for the whole study group (53 cases), for the patients with monolateral node positivity (36 cases), and for the patients showing only one positive node (19 cases). The diameter and the site of the metastasis were significantly correlated with survival in all three groups studied. Patients showing an intracapsular positivity or a size of metastasis less than 5 mm had a 5-year cancer-related survival of almost 90%, while patients showing a metastasis larger than 15 mm or an extracapsular site had a 20% survival. The results demonstrate that patients affected by invasive squamous cell vulvar cancer with positive nodes can be divided into two groups with a significantly different survival according to the histopathological pattern of lymph node invasion. PMID- 1612510 TI - Radical hysterectomy for cervical cancer: morbidity and survival in relation to weight and age. AB - The records of 123 patients with Stage I cervical cancer who underwent radical hysterectomy with pelvic lymphadenectomy and para-aortic node sampling from 1981 to 1988 were reviewed to assess the risks of surgery associated with increasing weight and age. Fifty-four patients were obese (20% or more over ideal body weight) and fourteen were elderly (age 65 or older). Previous abdominal/pelvic surgery and operative time were significantly increased in the obese patients (P less than 0.05). Increased weight was associated with increased blood loss (P = 0.06). Medical illnesses, transfusion rates, postoperative stay, intraoperative and postoperative complications (including wound infection and separation), long term complications, and 5-year survival rates were not significantly different in obese and nonobese women. Diabetes mellitus, hypertension, any medical illness, intraoperative complications (29% vs 3%), and postoperative ileus were significantly higher (P less than 0.05) in elderly patients. However, operative time, blood loss, transfusion rates, postoperative stay, postoperative complications (exclusive of ileus), long-term complications (13-21%), and 5-year survival rates (77-99%) were not significantly different when analyzed by age. We found no significant increase in morbidity of radical hysterectomy for Stage I cervical cancer in the obese patient and minimally increased morbidity in the elderly patient with no increase in long-term complications or decrease in survival. Obesity should not represent a contraindication to radical surgery in appropriately selected patients with cervical cancer. PMID- 1612511 TI - CA 125 measured before second-look laparotomy is an independent prognostic factor for survival in patients with epithelial ovarian cancer. AB - The prognostic significance of serum CA 125 level measured in the week before second-look operation was evaluated in 208 patients with invasive epithelial ovarian cancer. Serum CA 125 level was greater than 35 U/ml in 44.7% of patients. All patients with pathological complete response (PCR) had a serum CA 125 level less than or equal to 35 U/ml except one who developed lung metastases 2 months later. The sensitivity of serum CA 125 for identifying residual tumor at second look operations was 58%, the specificity was 98%, the predictive value of a positive test was 99%, and the predictive value of a negative test was 43%. By Cox regression analysis, tumor state of second look, serum CA 125 level, histologic type, FIGO stage, and tumor grade were identified as independent prognostic factors for survival. We conclude that measurement of serum CA 125 level after induction chemotherapy represents a noninvasive method to identify patients at high risk for subsequent death from ovarian cancer. As far as we know, this is the first report to identify serum CA 125 level as an independent prognostic factor at the time of second-look laparotomy. PMID- 1612512 TI - Peutz-Jeghers syndrome with ovarian sex cord tumor with annular tubules and cervical adenoma malignum. PMID- 1612513 TI - [Tumor metastases in axillary lymph nodes in unknown primary tumor]. PMID- 1612514 TI - [At the borderline between life and death: quality of life--terminal care]. PMID- 1612515 TI - [Antepartum CTG]. PMID- 1612516 TI - [Diagnosis and therapy of sterility. 1]. PMID- 1612517 TI - [Varicose veins and chronic venous insufficiency--a tour d'horizon]. PMID- 1612518 TI - [Lymphocele following pelvic and para-aortic lymph node excision from the viewpoint of the angiologist]. PMID- 1612519 TI - [Lymphocele following pelvic and/or para-aortic lymph node excision--incidence, treatment, prognostic factors]. PMID- 1612520 TI - [Disorders of urinary tract function following gynecologic oncologic therapy]. PMID- 1612521 TI - [Bone marrow depression following oncologic therapy]. PMID- 1612522 TI - [Sexual problems following gynecologic-oncologic therapy]. PMID- 1612523 TI - [Complications of radiotherapy in gynecologic oncology]. PMID- 1612524 TI - Effects of prolactin on secretion and synthesis of human chorionic gonadotropin in human term placentas in vitro: short-term increase in secretion, followed by medium-term suppression of synthesis and secretion. AB - We studied the influence of human prolactin on the secretion and de novo synthesis of human chorionic gonadotropin (hCG) in the human term placenta in culture. Placental tissue from 14 patients with uncomplicated pregnancies and deliveries was prepared mechanically, with addition of a Percoll gradient step. hCG levels were determined in the culture media and in the cytosolic fraction of cells by means of an enzyme immunoassay with coated beads. The amount of newly synthesized hCG was measured by the extent of incorporation of 35S-methionine into the hCG molecule. Our results showed that human prolactin had two different effects in vitro: between 1/2 and 1 h, prolactin slightly increased secretion of hCG into the culture medium without affecting de novo synthesis; after 2 h, prolactin began to cause a significant decrease in both secretion and de novo synthesis of hCG over several hours. It appears that both effects are receptor mediated, for ovine prolactin failed to produce any response. We conclude that prolactin is one of the main factors regulating the synthesis and secretion of hCG in the human trophoblast at term. PMID- 1612525 TI - Betamethasone-induced lecithin release in vitro from the fetal membranes. AB - Lecithin release from fetal membranes and placental tissue was assayed in basal conditions as well as under betamethasone administration. In the absence of the steroid, amnion and chorion released lecithin as a function of incubation time. Both tissues responded to betamethasone by increasing the lecithin release, the amnion exhibited a higher basal level and a greater responsiveness to the hormone than the chorion. Basal lecithin release from placental tissue was unaffected by any steroid concentration. PMID- 1612526 TI - Localization of 15-hydroxy prostaglandin dehydrogenase in human fetal membranes, decidua, and placenta during pregnancy. AB - Localization of NAD(+)-dependent 15-hydroxy prostaglandin dehydrogenase (type I PGDH) may influence local concentrations of bioactive eicosanoids within intrauterine tissues. In early pregnancy (6-9 weeks), IR-PGDH was localized by immunohistochemistry to syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast of placenta. At 23-30 weeks of gestation and at term IR-PGDH was present in syncytiotrophoblast and intermediate trophoblast, but not in cytotrophoblast in placenta. It was absent from amnion, and distributed within the trophoblast cell layer of extraplacental chorion variably at 23-30 weeks, but consistently at term. We speculate that PGDH is ideally localized to metabolize and to maintain low concentrations of primary prostaglandins in the fetal membranes for much of gestation. PMID- 1612527 TI - Tetraploidy in human placenta. A dilemma in molar and non-molar pregnancies. AB - 17 cases of partial molar pregnancy were analysed cytogenetically by the direct preparation method. Eight partial moles were triploid, 7 diploid/tetraploid mosaic, and 2 tetraploid. In the course of prenatal cytogenetic screening, out of 1,263 chorionic villus samplings, 2 tetraploid and 1 diploid/tetraploid cases were found. These cases of partial moles do not fit into the usual patterns of triploid partial moles. The findings presented here suggest that different causative factors may be involved in the origin of molar degenerations. These results also call to attention that tetraploidy is an existent and relatively common abnormality. PMID- 1612528 TI - Effect of serum from patients with endometriosis on the development of mouse embryos. AB - The effect of serum from patients with endometriosis on the in vitro development of 2-cell mouse embryos was evaluated in the present study. Embryos were cultured for 72 h in 5% serum supplement from patients with endometriosis, infertile patients with no evidence of endometriosis, and Ham's F-10 medium with no serum supplement. Significantly less embryos developed to the blastocyst stage at 72 h in the endometriosis group as compared with the nonendometriosis groups and Ham's F-10 medium (p less than 0.05). These results suggest the presence of one or more serum factors that are toxic to early embryonic development and thus may play a role in the infertility associated with endometriosis, especially with respect to early embryonic loss. PMID- 1612529 TI - Measurement of noradrenaline, dopamine and serotonin contents in follicular fluid of human graafian follicles after superovulation treatment. AB - We measured the noradrenaline (NA), serotonin (5-HT) and dopamine (DA) contents of 47 normally maturated and 16 cystically degenerated follicular fluid samples obtained from patients involved in the in vitro fertilization and gamete transfer program. The patients were given human menopausal gonadotropin (HMG), as a superovulation treatment, and 7,500 IU human chorionic gonadotropin (HCG) to induce ovulation 34-36 h prior to the follicular puncture done by laparoscope. The NA content of the normally developed follicles was 11.4 + 8.4 micrograms/100 ml on average. For cystically degenerated follicles, the following data were obtained: 1.1 + 0.7 micrograms/100 ml (p less than 0.001). 5-HT and DA contents in the preovulatory follicles are 14.3 +/- 8.9 and 19.3 +/- 8.2 micrograms/100 ml, respectively; at the same time, 5-HT and DA contents in the cystically degenerated follicles were 12.2 +/- 6.2 and 12.7 +/- 6.8 micrograms/100 ml, respectively. They suggest that the higher amount of NA in the follicular fluid might play an important role in the mechanism of ovulation, the regulation of postovulatory tubal motility and the release of progesterone from granulosa cells. PMID- 1612530 TI - Intranasal salmon calcitonin in postmenopausal osteoporosis: effect of different therapeutic regimens on vertebral and peripheral bone density. AB - Sixty postmenopausal women were randomly assigned to three types of treatment with intranasal salmon calcitonin (SCT) plus calcium 500 mg daily (group A: 100 IU daily of SCT; group B: 100 IU daily of SCT for alternate cycles of 2 months with a 1-month interval; group C: 100 IU daily of SCT for alternate cycles of 3 months of treatment followed by a 3-month interval) or calcium 500 mg daily alone (control group). Lumbar density significantly decreased in the control group while it maintained the initial value in both continuously or cyclically treated groups. The bone density of the proximal and distal forearm in treated and control groups did not show significant changes after 12 months. PMID- 1612531 TI - Increased rate of preterm deliveries in untreated women with luteal phase deficiencies. Preliminary report. PMID- 1612532 TI - Antibiotic concentration in maternal blood, cord blood and placental tissue in women with chorioamnionitis. PMID- 1612533 TI - Successful outcomes of pregnancy complicated with dermatomyositis. Case reports. AB - There are few reports in the literature of pregnancy in dermatomyositis (DM), in contrast with those of other connective tissue diseases. We describe 2 patients who had an established diagnosis of DM and then became pregnant. In these cases, both the fetal and maternal outcome were good, and differed from those in previously reported cases. PMID- 1612534 TI - Multiple follicles in an unstimulated cycle despite elevated gonadotropins in a perimenopausal female. AB - The presence of estrogen deficiency associated with elevated gonadotropins usually signifies menopause. However, there have been a few case reports of ovulation and pregnancy despite hypergonadotropic hypogonadism. Described herein is a case of a perimenopausal woman who not only failed to ovulate in response to clomiphene citrate therapy but also failed to generate a level of serum estradiol (E2) over 30 pg/ml. Following pharmacologic suppression of her elevated gonadotropins with ethinyl estradiol, she spontaneously formed 3 mature follicles, and her serum E2 climbed to 868 pg/ml. This case suggests that some perimenopausal women may respond to their own endogenous elevated gonadotropins as if they are taking ovulation-inducing drugs and may, as a consequence, form multiple follicles. PMID- 1612535 TI - Drinking behavior in the black howler monkey (Alouatta caraya). PMID- 1612536 TI - Termites as food for the thick-tailed bushbaby (Otolemur crassicaudatus) in Malawi. PMID- 1612537 TI - Variations in dental measurements between Saguinus species and their systematic relationships. AB - Multivariate analysis is applied to dental measurements of Saguinus species to analyse their systematic relationships. The shape distance between Saguinus midas midas and S. midas niger is larger than that between S. nigricollis and S. fuscicollis, both of which are generally recognized as valid species. In dental form, S. bicolor is the closest relative of S. midas. S. inustus is not linked to S. leucopus. S. geoffroyi and S. leucopus, as S. inustus shows closer affinity with S. labiatus and S. mystax than with the former 3 species. PMID- 1612538 TI - DNA fingerprinting reveals that infant care by male barbary macaques (Macaca sylvanus) is not paternal investment. PMID- 1612539 TI - Amino acids from mushrooms. PMID- 1612540 TI - [Intensive care medicine in advanced age from the viewpoint of the internist]. AB - BASIC REMARKS: The percentage of elderly patients in ICUs has doubled over the last 20 years; in the case of the over-seventy-year-olds it is at present about 30%. MAJOR DISCUSSION POINTS: The mean length of stay in the ICU and hospital, and the average costs incurred, are not significantly higher in the case of the elderly. With increasing age, mortality rises steadily, being about 20% for geriatric patients in the ICU, 37% in hospital, and 52, cumulative, after one year. Nevertheless, elderly patients benefit in particular from intensive care. Their relative mortality rate in comparison with the general population of the same age is only slightly elevated. In view of the very high mortality following cardiopulmonary resuscitation of geriatric patients, it would make good sense to limit the indication in particular cases. Quality of life after discharge from ICU care and thereafter is appreciably lower in comparison with younger patients, but acceptance of intensive care is very good among elderly patients, too. As a study we carried out in our "toxicological" ICU showed, prognostic scoring systems for the elderly are not particularly reliable, and the geriatric skills and the knowledge of the physician weigh heavier. CONCLUSIONS: We consider intensive care in the elderly to be both beneficial and efficient, for despite an increase in the mortality rate, a satisfactory quality of life is achieved. PMID- 1612541 TI - [Intensive care for geriatric patients--legal problems]. AB - Treatment of the geriatric patient in the intensive care unit always requires the prior permission of the patient, whose ability to give this must be carefully examined. If the patient is no longer able to do this, a social worker has to act for him/her. This person is appointed by the guardianship court and can agree to risky treatment on the patient's behalf only with the permission of the court. This also applies equally to measures that will constrain the patient's freedom. Only in the case of an emergency may the physician act immediately. The question as to terminating treatment and the considerable need of the will of the patient to do so is discussed. The importance of correct documentation is particularly emphasized. PMID- 1612542 TI - [Elderly patients--perioperative management from the viewpoint of the anesthetist]. AB - FUNDAMENTAL CONSIDERATIONS: The number of elderly people undergoing surgery has increased considerably over the last decades. At the same time, there has been a shift from more minor to major procedures. RANGE OF TOPICS: More intensive diagnostic evaluation (e.g. right heart catheter) during the preoperative phase is required to identify patients with an increased risk. Also in the postoperative phase, mortality can be reduced through intensive and more prolonged monitoring (e.g. Holter monitoring) and appropriate treatment. In the field of anesthesiology, age (greater than 70 years) is a risk factor in its own right, that is, apart from the concomitant diseases seen in the elderly patient. CONCLUSIONS: The elderly patient requires more intensive diagnostic evaluation and care both pre- and postoperatively. PMID- 1612543 TI - [Intensive care of geriatric patients in surgery]. AB - BASIC REMARKS: Concomitant cardiovascular and pulmonary diseases in particular represent a considerable risk to the postoperative course in the geriatric patient. MAIN DISCUSSION POINTS: The main aim of intensive care consists in the avoidance and treatment of systemic complications. In contrast, local surgical complications as the reason for intensive care are of secondary importance in the geriatric patient. In the postoperative phase, the main problems encountered by the geriatric patient affect the cardiovascular system and pulmonary function. Age-specific pathophysiological changes affecting the lungs and heart require prophylactic measures aimed at preventing atelectasis, bronchial pneumonia and edema. As a rule, patients of advanced age require such intensive care for one to three days. CONCLUSIONS: The perioperative care of the elderly patient comprises, where possible, preoperative preparation and, postoperatively, a specific prophylactic intensive care regimen. PMID- 1612544 TI - [Intensive therapy of elderly patients in neurosurgery. Specifics of the postoperative phase in advanced age]. AB - INTRODUCTION: Postoperative intensive care of the elderly neurosurgical patient differs considerably from that of the younger patient. INVESTIGATION: Analysis of 106 patients aged between 68 and 92 years. RESULTS: In addition to the cardiopulmonary risk factors, the age-specific changes in the brain have an effect on the spectrum of postoperative complications. Age-related atrophy of the brain and in increase in the fragility of blood vessels due to degenerative processes increase the risk of subdural and intracerebral hemorrhage. The amount of time spent in the intensive care unit as a percentage of overall hospitalization is, at 50%, appreciably greater than that of younger patients. Intensive monitoring, including intracranial pressure and transcranial Doppler ultrasonography are useful for detecting intracranial complications at an early stage. CONCLUSIONS: Despite the appreciably greater duration of postoperative intensive care in the elderly, the overall outcome is comparable with that seen in younger patients in many neurosurgical conditions. PMID- 1612545 TI - [New guidelines for treatment of fractures. Part 5. Pelvis and hip joint]. PMID- 1612547 TI - [Defense mechanism and tissue destruction in periodontitis]. PMID- 1612546 TI - [Improvement of hemorheology with ginkgo biloba extract. Decreasing a cardiovascular risk factor]. AB - STUDY DESIGN: Open prospective study. PATIENTS: 20 outpatients with a long history of elevated fibrinogen levels and plasma viscosity, and a variety of underlying diseases. INTERVENTION: Treatment with the special ginkgo biloba extract (EGb 761), 240 mg tablets a day for a period of 12 weeks. RESULTS: The clinical diagnoses included coronary heart disease, hypertension, hypercholesterolemia and diabetes mellitus. A significant improvement in the fibrinogen levels and hemorrheological properties was seen. The medication can thus positively influence these cardiovascular risk factors over the long term. PMID- 1612548 TI - [A study on the mechanism of microvibration changes in patients with eating disorders]. AB - Microvibration (MV), which is a minute vibration observed on the human body surface, has been used clinically as a simple test for the autonomic nervous system function in psychosomatic medicine. The analogue frequency analysis has shown four different MV types in healthy subjects, depending on a major frequency component of MV. Although N type, a MV type with predominant frequencies being in the alpha band, is most common in healthy subjects, we have found that F type, the predominant frequencies being in the fast frequency (beta) band, is most common in patients with psychosomatic disorders, particularly in those with eating disorders. We have developed a system of digital frequency analyses of MV on a personal computer, in which the Fast Fourier Transform (FFT) and the reverse FFT are employed. In this study, the physiological significance of MV changes was investigated in patients with eating disorders, utilizing frequency analysis methods of the analogue and digital systems. The following results and conclusions were obtained. (1) A multiple regression analysis was performed to clarify the relationship between somatic severity (body weight change) and MV frequency bands by the analogue method in 57 patients with eating disorders. Percent change of body weight (% BW) was used as a target (dependent) variable, and 6 frequency bands of MV energy % were used as explanatory (independent) variables. The alpha 1 (7.5-8.5 Hz) and the beta (13-20 Hz) bands were selected as having a high explanatory power for % BW, with the alpha 1 band being greater than the beta band. This indicated that the reduction of % BW had a higher correlation with the decrease of the alpha 1 band than with the increase of the beta band. (2) The reverse FFT of a MV power spectrum was calculated with the digital method to extract frequency bands that was time-locked with ECG. This revealed that the time-locked oscillations were always found in the alpha band in either normal subjects or patients with eating disorders, regardless of the MV type. This indicated that the ballistocardiographic component of MV is included in the alpha band. (3) Putting all these results together, it is concluded that, in patients with eating disorders, the predominance of the beta band in MV (the F type) is caused by the decrease of the ballistocardiographic component of MV. PMID- 1612549 TI - [The association between deficiency of terminal complement components and the occurrence of meningococcal meningitis]. AB - Seventeen patients with sporadic meningococcal meningitis, registered in Fukuoka city, were studied for complement deficiency. Four of the seventeen had a selective deficiency of the ninth component of the complement (C9), four had a deficiency of the seventh component of the complement (C7), and one had a deficiency of the fifth component of the complement (C5) as determined by both hemolytic and antigenic assay. Family studies suggested that these complement deficiencies in the present study were hereditary. Based on the incidence (0.036% of homozygous C9 deficiency in Fukuoka (171 C9 deficient individuals of 475, 886 blood donors), we have concluded that patients with C9 deficiency are more susceptible to meningococcal meningitis than normal individuals (p less than 0.001). In addition, the present study further supports that complement deficiency is common in patients with sporadic meningococcal meningitis. PMID- 1612550 TI - [Effects of steroid therapy in IgA nephropathy]. AB - In order to estimate the effects of corticosteroid therapy in IgA nephropathy cases with daily urinary protein excretion of 1.0 g/day or more. 26 patients (8 men and 18 women, aged 32.6 +/- 14.0 years old) were subjected to this study. The results obtained were as follows: Urinary protein excretion after 1 year from the beginning of steroid therapy (1.56 +/- 1.14 g/day) was significantly (p less than 0.05) lower than that at the beginning of the therapy (4.61 +/- 6.01 g/day). In serum creatinine levels, there was no statistically significant difference with them between at the beginning (1.15 +/- 0.48 mg/dl) of steroid therapy and at the time of 1 year after (1.05 +/- 0.34 mg/dl) the therapy. As for the outcome at the end of this study setting (mean follow-up duration: 3.7 +/- 2.6 years), complete remission was attained in 7 cases, improvement in 5 cases, unchanged condition in 11 cases, increased urinary protein excretion in 2 cases and aggravated renal function in 1 case. In clinical findings at the renal biopsy, duration of the disease (3.4 +/- 1.6 months) in complete remission cases before biopsy was significantly (p less than 0.01) shorter than that in unchanged cases (65.0 +/- 40.0 months). In histological findings, rate of global sclerosing glomeruli (2.6 +/- 4.6%) in complete remission cases was significantly (p less than 0.05) lower than that (24.6 +/- 23.1%) in unchanged cases. These results suggest that steroid therapy in IgA nephropathy with persistent proteinuria of 1.0 g/day or more is beneficial, especially in cases that are in early stage of the disease with lower rate of global sclerosing glomeruli. PMID- 1612551 TI - Immunotherapy with ciamexon in the non obese diabetic (NOD) mouse. AB - Ciamexon (CMX), a new immunomodulatory compound acting mainly on B-lymphocytes was given orally to 42 NOD mice divided into three sex and litter matched groups (A: 0.3 mg/mouse/day CMX, B: 1.5 mg/mouse/day CMX, C: control) from 7 weeks of age. Animals were followed up for evaluation of diabetes incidence up to 32 weeks of age. There was a tendency for a delayed onset of hyperglycemia in mice of group B up to 26 weeks of age; however no significant difference in the cumulative incidence of diabetes at 32 weeks of age was observed (A: 57.5%, B: 38.5%, C: 38.5%). No differences were found in the number of infiltrated islets in animals culled at 10 weeks of age treated with CMX from 4 weeks of age. We conclude that CMX does not modify the course of insulitis and diabetes incidence in NOD mice although though the appearance of glycosuria was delayed by this treatment. PMID- 1612552 TI - Thyroid hormone increases transcription of growth hormone mRNA in rainbow trout pituitary. AB - Treatment of young rainbow trout (Oncorhynchus mykiss) fish for one week with thyroid hormone (T3) (3,3',5-triiodo-L-thyronine) increased the steady state levels of mRNA for growth hormone in the pituitary 3-4 times as compared to control groups. The steady state levels of growth hormone in the pituitary and in the plasma, were not significantly altered. This implicates the existence in fish of a molecular mechanism of transcriptional stimulation of the GH gene by thyroid hormone, similar to that observed in the rat. These results may explain part of the known anabolic effects of thyroid hormone in fish. PMID- 1612553 TI - Amelioration of some metabolic effects produced by hyperthyroidism in late pregnant rats and their fetuses. Effects on lipids and proteins. AB - We have studied the effect of 40-45 days administration of 1 mg/kg thyroxine on protein and lipid metabolism in liver, heart, lungs, kidneys and adrenal glands of virgin and 21-day pregnant rats and their fetuses and placentae. The chronic administration of thyroid hormone produced significant increases in serum T3 and T4 in both groups as well as in organ weights and protein concentrations in virgin rats, but much smaller modifications in pregnant ones. Hyperthyroidism decreased the weight of fetal livers and increased that of placentae; protein content was increased in all fetal organs. Hyperthyroidism induced increases in phospholipid concentrations in all the organs and in total lipids only in liver and heart of adult rats, which were not counteracted by pregnancy. Pregnant rats had increases in total lipids in liver and kidneys and in adrenal phospholipids. In hyperthyroid fetuses there was an increase in hepatic total lipids and no changes in phospholipids. Hepatic lipogenesis (measured by in vivo incorporation of 3H2O into lipids) was increased by hyperthyroidism in virgin and pregnant rats, but the increase was significantly smaller in the pregnant hyperthyroid rats compared with the virgin ones. Fetal lipogenesis in liver and lung was not changed. In addition, an increase was observed in lipogenic enzyme (fatty acid synthetase and glucose-6-phosphate dehydrogenase) activities in hyperthyroid virgin rats which was prevented by pregnancy. In fetuses only pulmonary glucose-6 phosphate dehydrogenase was increased when expressed in terms of tissue weight. Our results indicate that the metabolic effect of hyperthyroidism is attenuated in pregnant rats and their fetuses, when compared with adult virgin rats, in most of the parameters studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612554 TI - Activity of some lysosomal enzymes in plasma and leucocytes of rabbits exposed to effect of retinol and hydrocortisone. AB - Observing activity of some lysosomal enzymes in blood serum and leucocytes of rabbits subjected to injection of 200,000 units of retinol and 25 mg of hydrocortisone/kg of body weight it was found that: 1. In the effect of retinol administration there was an increase in the activity AP, BGAL, BGLU, AspAT and lipase in blood serum after 72 hours and NAGL after 168 hours while in leucocytes BGAL and NAGL after 72 hours and AGAL after 168 hours. 2. As a result of hydrocortisone injection the activity of all the enzymes examined (except Ala-Na) in blood serum increased markedly already after 24-48 hours. 3. In leucocytes hydrocortisone caused a significant increase in the activity of AP, BGRD, NAGL, BGAL, AGAL and cathepsin D. 4. The glucose level in blood plasma decreased after 48 hours and 120 hours after hydrocortisone injection and 168 hours after retinol injection. PMID- 1612555 TI - Peripheral glucose metabolism in patients with insulin resistance and acanthosis nigricans. AB - The present study was designed to determine forearm muscle glucose uptake and oxidation during the postabsorptive state and after an oral glucose challenge in patients with type A insulin resistance and acanthosis nigricans. Nine normal subjects and six acanthotic patients were studied after an overnight fast (12-14 h) and during 3 hours after ingestion of 75 g of glucose. Peripheral glucose metabolism was analysed by the forearm technique to estimate muscle exchange of substrate combined with indirect calorimetry in forearm. Two patients (1 and 6) with insulin resistance and acanthosis nigricans had impaired glucose tolerance. All other patients and normals revealed normal glucose tolerance during the tests. Decreased forearm muscle glucose uptake was observed in patients 1 and 6 compared to normal subjects (6.3 and 51.1 vs 127.7 +/- 10.1 mg/100 ml forearm.3 h, respectively). Decreased forearm muscle glucose oxidation was also observed in patient 1 as well as in patient 3 who showed normal glucose tolerance. Serum FFA levels were elevated in patient 1 but not in patient 3 and in the other acanthotic patients compared to the normal subjects. Serum insulin levels were significantly higher in acanthotic patients than in normals before and after glucose loading. The results of the present study revealed that two of six patients with type A insulin resistance and acanthosis nigricans who exhibited glucose intolerance also showed a decrease in peripheral muscle glucose uptake and nonoxidative glucose metabolism. Another patient (3) with normal glucose tolerance showed impaired muscle glucose oxidation but unaltered muscle glucose uptake and nonoxidative metabolism during the 3 hours of study.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612556 TI - Effect of LHRH on plasma 7B2 in patients with gonadotropin-producing pituitary adenomas. AB - Plasma immunoreactive (IR)-7B2 was measured in four patients with gonadotropin producing pituitary adenomas. The basal level of plasma IR-7B2 was elevated in one of the four patients. Hyperresponse of plasma IR-7B2 to LHRH or LHRH/TRH was noted in two patients tested. 7B2 was positively stained in a paraffin-embedded section of gonadotropin-producing pituitary adenoma obtained at surgery. These findings suggest that 7B2 is produced in gonadotropin-producing pituitary adenomas and secreted into the blood stream under certain conditions. 7B2 may be a useful marker for gonadotropin-producing pituitary adenomas. PMID- 1612557 TI - TSH producing pituitary tumor: biochemical diagnosis and long-term medical management with octreotide. AB - A 50 year old man with hyperthyroidism secondary to inappropriate secretion of TSH is described. On presentation T3 (42.1 nmol/L), T4 (265 nmol/L) and TSH (17.9 mU/L) were all markedly elevated. A diagnosis of a TSH-secreting pituitary tumor was suspected on the basis of a blunted TSH response to TRH and the absence of suppression of TSH by T3 or bromocriptine, but TSH/alpha subunit molar ratios were uncharacteristically less than 1. Nevertheless, the presence of a tumor was confirmed by computed tomography which demonstrated a 15 mm pituitary macroadenoma. The patient was treated with octreotide which resulted in normalisation of thyroid hormone levels. The duration of action of a single 100 micrograms injection of octreotide was at least 56 hours. The suppression of thyroid hormone levels was similar regardless of the treatment regimen with octreotide (100 micrograms tid, 250 micrograms bid, 100 micrograms bid and continuous subcutaneous infusion (CSI] and no escape was observed during a 16 month treatment period. TSH alpha subunit concentrations were also suppressed during long-term treatment with octreotide (3.3 micrograms/L falling to 1.1 micrograms/L), although no acute changes were noted after administration of single dose octreotide 100 micrograms. Three times the octreotide therapy was discontinued. The incremental rise in TSH and the maximum level of TSH achieved was less on each subsequent occasion, suggesting a suppressive effect of octreotide on the tumor itself. Despite suppression of TSH with octreotide over a 13 month period the pituitary tumor showed no shrinkage on repeat MRI scanning. In conclusion, this patient demonstrates that the differential diagnosis of inappropriate TSH secretion based only on biochemical test may be unreliable.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612558 TI - Plasmapheresis induces high reverse T3 levels in euthyroid and hyperthyroid patients. PMID- 1612559 TI - Is the adrenal cortex a putative site for the action of interleukin-1? PMID- 1612560 TI - Suppressive effect of vasopressin on ketosis in diabetic rats. AB - In order to clarify if vasopressin (VP) plays a role in the pathophysiology of hyperosmolar nonketotic diabetic coma (HNDC), VP has been infused to diabetic rats and plasma levels of glucose (PG), ketone bodies, FFA and glucagon were determined. High-dose VP infusion (1.2 U/kg/h) caused gradual elevation of PG (60%) and glucagon levels (600%), while ketone bodies showed transient decrease (20%) at 30 min. Under the suppression of endogenous glucagon secretion by constant infusion of somatostatin (100 micrograms/kg/h), high dose VP showed 25% increase in PG levels and 30% reduction of ketone body levels for the subsequent VP infusion for 1.5 hour. Low-dose VP infusion (0.06 U/kg/h) had no hyperglycemic effect, but suppressed ketosis (20%) in the same condition. There were no changes in plasma FFA concentrations, indicating no significant effect of VP on lipolysis. The results indicate that VP often elevated in HNDC may play an important role for the pathophysiology of HNDC through suppression of hepatic ketogenesis. PMID- 1612561 TI - Hormonal responses to removal of a breeding male in the cooperatively breeding white-browed sparrow weaver, Plocepasser mahali. AB - The white-browed sparrow weaver (Plocepasser mahali) is a cooperatively breeding Ploceid finch that lives in groups of up to 11 individuals. Each group consists of a dominant breeding male and female and a varying number of nonreproductive birds that help feed young and defend the group territory. Experimental removal of the dominant male resulted in attempts by other males to take over the group. Removal of a subordinate, nonbreeding male, as a control, resulted in no change of status among group members. During takeover, there was a transitory increase in plasma levels of luteinizing hormone in the new dominant male, but no change in testosterone levels. As reported in previous investigations, dominant males tended to have higher levels of testosterone than females or subordinate males, but this was not related to the heightened aggression of the takeover. Plasma levels of luteinizing hormone, testosterone, and corticosterone did not differ between the other status groups. The possibility that luteinizing hormone, or a hitherto unidentified androgen, may regulate aggression in the white-browed sparrow weaver is discussed. PMID- 1612562 TI - Sex steroids and vasotocin interact in a female amphibian (Taricha granulosa) to elicit female-like egg-laying behavior or male-like courtship. AB - Female egg-laying behaviors and male amplectic clasping behaviors in the rough skinned newt (Taricha granulosa) are similar in that animals clasp an object. In the case of egg-laying, females clasp submerged inanimate objects, whereas in amplexus, males clasp conspecific females. Considering these behavioral similarities and differences, we investigated the possibility that gonadal steroids and vasotocin (AVT) interact to control egg-laying behaviors, as has been shown for the control of amplexus in Taricha males. Intact, gravid T. granulosa females injected ip with AVT, unlike those injected with saline, exhibited egg-laying behaviors and oviposition. In ovariectomy-steroid-implant studies, no saline-injected female exhibited egg-laying behaviors, whereas AVT injected ovariectomized females exhibited egg-laying behaviors if implanted with estradiol (E2), testosterone, or dihydrotestosterone (DHT), and not if implanted with empty capsules. When given a choice between clasping aquatic vegetation or other females (amplectic clasping), following an AVT injection, unoperated and sham-operated control females and ovariectomized females with E2 implants did not preferentially clasp aquatic vegetation over other females. In contrast, AVT injected ovariectomized females with DHT implants preferentially clasped other females. Thus, exposure of Taricha females to estrogens or androgens appears to determine whether the AVT-induced clasping is egg-laying or amplectic clasping. PMID- 1612563 TI - Behavioral, endocrine, and immunological correlates of immigration by an aggressive male into a natural primate group. AB - A very aggressive young adult male entered one of three long-term study groups of yellow baboons. Papio cynocephalus, approximately 3 weeks after an immobilization project began. The immigrant male's rate of agonistic encounters was appreciably higher than average, and these interactions disproportionately involved adult females as targets. Basal cortisol concentrations were higher and total lymphocyte counts lower for individuals immobilized during the immigration situation than for other individuals; these effects were greater for females than for males. Among animals whose endocrine data were obtained during the immigration period, some were specific targets of the immigrant male's aggression and others were not. Lymphocyte counts were significantly lower for those individuals who were victims of the male's aggression than for noninvolved individuals; a nonsignificant tendency toward higher basal cortisol concentrations for victims was observed as well. The immigrant male himself had a high basal cortisol concentration, a low lymphocyte count, and a testosterone concentration that was triple the average for adult males and almost double the second highest value in the population. PMID- 1612564 TI - Behavioral demasculinization of female quail is induced by estrogens: studies with the new aromatase inhibitor, R76713. AB - The injection before Day 12 of incubation of estradiol benzoate (EB) into Japanese quail eggs produces a complete behavioral demasculinization of adult males that will hatch from these eggs. These males never show copulatory behavior even after administration of high levels of exogenous testosterone (T). It is usually assumed that such a demasculinization normally takes place in female embryos under the influence of endogenous estrogens but few experimental data are available to confirm the validity of this model. A series of four experiments was performed during which R76713, a triazole derivative that specifically inhibits aromatase (estrogen synthetase) activity, was injected into quail eggs at different stages of incubation to prevent the production of endogenous estrogens. The consequences of these embryonic treatments on the T-activated sexual behavior in adults were then quantified. When injected before Day 12 of incubation, R76713 completely blocked the behavioral demasculinization of females without affecting the behavior of the males. After a treatment with T, almost all R76713-treated females showed as adults a masculine copulatory behavior that was undistinguishable from the behavior of intact males. This effect was fully reversed by the injection in egg of EB demonstrating that the effects of R76713 were specifically due to the suppression of endogenous estrogens. Injection of R76713 during the late phase of the incubation (Day 12 or Day 15) only maintained weak copulatory behavior in females which confirmed that the behavioral demasculinization in quail takes place mainly though not exclusively during the early stages of ontogeny. In a last experiment, we combined an early R76713 treatment with an injection of EB either on Day 9 or on Day 14 of incubation. This showed that the sensitivity to differentiating effects of estrogens varies with age in a sexually differentiated manner. The EB injection on Day 9 demasculinized both male and female embryos. If this injection was delayed until Day 14, it was no longer effective in males but still caused a partial demasculinization of females. This demonstrates that even if females are not yet behaviorally demasculinized on Day 9 of incubation (suppression of aromatase activity at that age will maintain the behavior), their sensitivity to estrogens is already different from that of males. PMID- 1612565 TI - Differential effects of testosterone metabolites upon the size of sexually dimorphic motoneurons in adulthood. AB - This study examined the effect of testosterone and two of its metabolites on the size of motoneurons in the sexually dimorphic spinal nucleus of the bulbocavernosus (SNB) in adult male rats. Treatment of castrates with either testosterone or dihydrotestosterone maintained SNB cell size, although testosterone was more effective in this regard. However, estradiol, either alone or in conjunction with dihydrotestosterone treatment, had no effect on the size of the somata or nuclei of SNB motoneurons. These results indicate that testosterone affects SNB cell size by interacting with androgen receptors and that aromatized metabolites of testosterone are not involved in this aspect of motoneuronal plasticity in adulthood. Because the penile reflexes mediated by the SNB neuromuscular system are also sensitive to androgen but not estrogen treatment, morphological changes in SNB cells may contribute to the androgenic modulation of these reflexes. PMID- 1612566 TI - Conditioned place preference induced by sexual interaction in female rats. AB - The present study was undertaken to establish whether the conditioned place preference paradigm can be utilized to investigate and elucidate the neuroendocrine basis of the appetitive elements of female sexual behavior. Females were exposed to a male with which copulation occurred in a distinctive compartment of the place preference apparatus and did not receive an incentive in the alternative compartment. After six pairings to each compartment a place preference test was conducted. Both estradiol benzoate and estradiol benzoate plus progesterone treated, ovariectomized females showed a preference for the compartment associated with sexual interaction. A second group of estradiol plus progesterone treated females was exposed to a male with which copulation occurred in one compartment of the place preference apparatus and to a sexually active, but caged, male in the other. The females tended to prefer the compartment paired with the caged male. After noncontingent intromissions, immediately preceding an additional test, the females showed a place preference for the compartment paired with sexual interaction. The presented observations indicate the potential use of the place preference procedure in studying opposing motivational processes associated with the unconditioned sequence of responses that characterize the species-specific pattern of sexual behavior. PMID- 1612567 TI - Sex differences in odor-stimulated flank marking in the golden hamster (Mesocricetus auratus). AB - To determine whether sex differences exist in the frequency of odor-stimulated flank marking, intact male and female hamsters were exposed to the recently vacated home cages of male stimulus hamsters for a 10-min test on 4 consecutive days. Females were found to mark at significantly higher levels than males. To investigate the role of gonadal hormones in the sex differences in flank marking, gonadectomized male and female hamsters were implanted with Silastic capsules containing estradiol or testosterone. Females exhibited twofold higher levels of odor-stimulated flank marking than males, and the amount of flank marking was significantly higher when the hamsters were administered testosterone than when they were administered estradiol. These data demonstrate that sex differences exist in the frequency of flank marking stimulated by the odors of male hamsters, and that these sex differences do not appear to result from the typical sex specific patterns of circulating levels of estradiol and testosterone. PMID- 1612569 TI - Estradiol concentrations, fat deposits, and reproductive strategies in male rhesus macaques. AB - Squirrel monkeys (Saimiri spp.) are thought to undergo a unique pattern of seasonal weight change among the Primates that reflects a fatted male phenomenon. But many male mammals, including rhesus macaques (Macaca mulatta), undergo circannual weight changes concurrent with mating season activity. Four adult male rhesus macaques living in a heterosexual social group in an outdoor enclosure were studied over a 2-year period in order to ascertain potential mechanisms underlying seasonal weight changes. Alterations in weight were significantly correlated with changes in abdominal fat levels and in body mass index. Neither testosterone nor estradiol fluctuations were correlated with weight changes, but estradiol levels were significantly correlated with body mass index. The annual profile of changes in abdominal fat level reflected the annual profile of variation in circulating estradiol levels. The fatted male phenomenon appears to characterize circannual weight fluctuations in rhesus macaques. Seasonal weight changes resulting from fat deposition are suggested to provide a substrate for adipose tissue aromatization that yields elevated estradiol levels and enables males to forego feeding and concentrate their energy budgets on activities directly related to mate acquisition and retention. PMID- 1612568 TI - Urine-marking by female mice throughout their reproductive cycle. AB - It is commonly believed that the scent-marking activity of female mammals is elevated when they are sexually receptive, yet urine-marking by female mice does not vary in relation to their estrous cycles. We examined the marking behavior of female mice during their reproductive cycle with attention to their postpartum period of sexual receptivity. In the first experiment, females were allowed to mark prior to mating, during gestation, on the evening of parturition, during lactation, and after weaning their pups. They were exposed to a male or female mouse or nothing at each testing period in a counter-balanced fashion. Overall, the subjects marked most frequently in the presence of a male stimulus; their marking rates did not differ when they were exposed to another female or to nothing. The females' marking remained relatively steady through gestation, declined dramatically at parturition, then gradually returned to the levels observed prior to mating. In the second experiment, multiparous females were allowed to mark while they were simultaneously lactating and pregnant. Compared to unmated females, the subjects' marking frequency was low at parturition, declined further to its lowest level about 1 week later, then regained the preceding low level prior to weaning the initial litter and delivering the next. Together these results demonstrate that urine-marking by female mice is diminished just after parturition. Thus, in contrast to some other species, the marking behavior of female mice apparently is not enhanced around the time they are sexually receptive. Because female mice generally mark most frequently when males are nearby, we postulate that a major function of this behavior is to evoke endocrine and behavioral responses in proximate males rather than to attract distant males. PMID- 1612570 TI - Socially stimulated androgen surges in male hamsters: the roles of vaginal secretions, behavioral interactions, and housing conditions. AB - The sources of cues necessary for elicitation of androgen surges and sexual behavior in male golden hamsters (Mesocricetus auratus) were investigated. Circulating androgen levels were measured in males after interactions with other males or several types of estrous females: intact females, vaginectomized females, or vaginectomized females scented with vaginal secretions. All groups of males that interacted with estrous females demonstrated significant elevations in androgens whereas those that interacted with other males did not. Thus, the presence of vaginal secretions is not necessary for the elicitation of androgen surges in sexually experienced male hamsters. Individual differences in sexual performance were not correlated with the degree of change in androgen levels, suggesting that such hormonal responses are not graded but are all-or-none. Housing males in isolation from females did not alter either baseline androgen levels or the magnitude of androgen responses caused by interactions with females. PMID- 1612571 TI - On lumping and splitting. PMID- 1612572 TI - The Bethesda System for reporting cervical/vaginal cytologic diagnoses: report of the 1991 Bethesda workshop. The Bethesda System Editorial Committee. PMID- 1612573 TI - A microsporidian previously undescribed in humans, infecting enterocytes and macrophages, and associated with diarrhea in an acquired immunodeficiency syndrome patient. AB - To date, the only microsporidian that has been associated with diarrhea and weight loss in acquired immunodeficiency syndrome patients is the newly identified Enterocytozoon bieneusi. A second species is now described that was associated with intestinal symptoms in a 32-year-old, human immunodeficiency virus- seropositive, Native American male homosexual. Stool studies and routine light microscopy of multiple small intestinal biopsies that showed atrophy with acute and chronic inflammation were without apparent pathogens. Light microscopy of semi-thin plastic sections, cytochemical stains of paraffin sections, and ultrastructural studies revealed extensive microsporidial infection of enterocytes and submucosal macrophages. No other pathogens were identified. Unlike E bieneusi, this microsporidian appeared to develop within septated parasitophorous vacuoles, and lacked polar disks and clear clefts. It most closely resembled, but was distinguishable from, members of the genus Encephalitozoon. Awareness of the microsporidia as potential opportunists in acquired immunodeficiency syndrome patients is increasing the incidence of identification of these organisms. PMID- 1612574 TI - Radiation therapy for nasopharyngeal carcinoma: histologic appearances and patterns of tumor regression. AB - Nasopharyngeal carcinoma is a common malignancy in Hong Kong and is treated by external radiotherapy. After 6.5 weeks of radiotherapy, the nasopharynx of 100 patients was examined and biopsy specimens were taken. All patients had repeated examination and biopsies done every 2 weeks until exophytic tumor was not seen and biopsy samples were negative on more than one examination of the nasopharynx. The interval between the cessation of therapy and biopsy ranged from 1 day to 11 weeks. Twenty-three patients had atypical findings and five of these had residual tumor requiring gold grain implantation brachytherapy. We identified a number of distinct pathologic changes in the post-biopsy material. Most of these changes disappeared 8 weeks after the cessation of therapy, but the presence of residual tumor after this time was an indication for subsequent therapy. If the date of the first biopsy was delayed until 6 weeks after the completion of radiotherapy, the percentage of atypical biopsies containing residual tumor rose from 21% to 55%. The posttreatment biopsy should be performed twice, as four patients had negative biopsy findings due to sampling error. PMID- 1612575 TI - Stromal neoplasms of the rectum and anal canal. AB - Nineteen mural-based stromal tumors of the rectum and anal canal were reviewed, with the objective of delineating pathologic features discriminative of malignancy in these uncommon neoplasms. Ten locally excised tumors failed to recur during long-term follow-up and were considered benign. All occurred in the submucosa and ranged in size from 1.0 to 7.0 cm (mean, 2.1 cm). Three were sparsely cellular; seven had the appearance of gastric-type cellular leiomyomas. All lacked nuclear atypia and displayed mitotic activity not exceeding 1 mitosis/50 high-power microscopic fields. In contrast, of nine tumors exhibiting malignant behavior, eight (89%) were located in the muscularis propria. Their mean size was 4.5 cm (range, 1.6 to 11 cm). Necrosis was present in six tumors (67%). Seven sarcomas retained a cellular leiomyomatous appearance but exhibited moderate cytologic atypia. Mitotic counts ranged from 5 to 58 mitoses/50 high power microscopic fields. Three locally excised sarcomas recurred in the rectum at 2, 2, and 7 years. In five patients tumor recurred in the pelvis. Five patients died of disease 0.67, 1.2, 3, 5, and 11 years post-diagnosis. One patient died with sarcoma at 31 years. Three patients are without evidence of recurrent neoplasm 5, 5, and 7 years postresection. Our data indicate that not all anorectal, mural-based stromal neoplasms are a priori malignant. While location within the muscularis propria, size, nuclear atypia, and tumoral necrosis correlate with malignancy, mitotic activity is the cardinal indicator of sarcomatous behavior in stromal neoplasms of the rectum and anal canal. PMID- 1612576 TI - Morphology of graft arteriosclerosis in cardiac transplant recipients. AB - The morphologic features of graft arteriosclerosis (GA) and other vascular lesions were semiquantitatively evaluated. Five failed cardiac allografts attributable to GA and five other allografts were obtained from nine autopsies and one surgical explanation. The subjects, aged 4.5 to 67 years, had a mean allograft survival of 735 +/- 184 days. A total of 1,174 arterial and 754 venous cross-sections were reviewed. Intimal fibrosis (nine cases, 254 arteries, and 118 veins), fibrofatty plaques (eight cases and 35 arteries), and cellular intima thickening and concentric foam cell lesions (eight cases, 326 arteries, and 20 veins) were seen. Cellular lesions contained T lymphocytes, monocytes, and cells of smooth muscle cell origin detected by staining using the immunoperoxidase technique. Allografts with severe GA had a greater luminal stenosis in epicardial arteries (P less than .05), greater cellular proliferation in large mural arterial lesions (P less than .004), and more foam cell lesions in both arteries (P less than .06) and veins (P less than .03) than other allografts. Medical fibrosis and thinning were present in six allografts. Severity of acute rejection (P less than .01) was correlated with the presence of GA. The morphology and distribution of GA is heterogeneous, with evidence supporting an immune-mediated pathogenesis. PMID- 1612577 TI - Sucrase-isomaltase expression in chronic ulcerative colitis and dysplasia. AB - Sucrase-isomaltase (SI) is a mucosal disaccharidase that is present in normal small intestine and fetal colon. It also has been noted in colonic adenomas and adenocarcinomas. We used a polyclonal antibody to human SI to investigate enzyme presence and utility in detecting dysplastic changes in chronic ulcerative colitis. Sections from 32 cases were reviewed for the presence or absence of active colitis and dysplasia. Immunostaining of these cases for SI was performed and the results were reported based on location of immunoreactivity (ie, membrane and cytoplasmic staining in superficial and crypt epithelial cells) and percentage of positivity. Of 81 sections examined, 48 were rated negative for dysplasia (23 inactive colitis, 20 active, and five probably negative) and 28 were rated positive (eight low grade and 20 high grade). Surface membrane staining of epithelial cells was noted in all 28 dysplastic slides and positive cases (sensitivity, 100%) but also in 29 of 48 negative sections (P less than .001). In contrast, cytoplasmic positivity was present in 25 of 28 dysplastic and in only two of 48 negative slides (P less than .0001). The presence of cytoplasmic staining of SI in the superficial or crypt cells revealed a sensitivity of 92% and a specificity of 94%. There were five additional sections rated as indefinite for dysplasia (probably positive or unknown); two showed staining patterns typical of negative slides and three showed positive staining patterns. Of the 18 samples of transitional mucosa next to areas of dysplasia, surface membrane staining of SI was seen in all samples and cytoplasmic staining was seen in 15. We conclude that membrane staining of SI can be detected in inflammatory, regenerative, and dysplastic mucosa in ulcerative colitis. Cytoplasmic staining, however, correlates strongly with the presence of dysplastic change and may help in its detection. PMID- 1612578 TI - Diabetic mastopathy: a distinctive clinicopathologic entity. AB - Insulin-dependent diabetics may manifest evidence of autoimmune diseases involving endocrine or other organs. Rare cases of a peculiar fibrous and inflammatory lesion of the breast in diabetic patients have been previously described; however, the pathologic and clinical features that uniquely characterize these cases have not been defined or distinguished from other chronic inflammatory and fibrosing conditions in the breast. We studied eight patients with breast masses and longstanding insulin-dependent diabetes and compared them with 36 nondiabetic or short-duration diabetic patients with fibrosis and chronic mastitis. The longstanding diabetic patients presented with clinical breast masses ranging in size from 2 to 6 cm. Six of the eight patients had documented diabetic nephropathy, retinopathy, or neuropathy. Pathologically, these lesions showed lymphocytic lobulitis and ductitis, lymphocytic vasculitis (predominantly B cell), and dense keloid-like fibrosis that in many cases (six of eight) contained peculiar epithelioid cells embedded in dense fibrous stroma. We have provisionally labeled these cells "epithelioid fibroblasts" (EFBs). Although the features of lymphocytic lobulitis, ductitis, and/or vasculitis may occasionally be encountered in nondiabetic breast biopsies, EFBs appear to be unique to the diabetic condition. Control cases of chronic mastitis in nondiabetic or short-duration diabetes patients failed to show the complete constellation of lymphocytic lobulitis and ductitis, vasculitis, keloidal fibrosis, and EFBs. Diabetic mastopathy may represent an immune reaction to abnormal matrix accumulation. A hypothesis is presented. PMID- 1612579 TI - Utility of immunohistochemistry in distinguishing ovarian sertoli-stromal cell tumors from carcinosarcomas. AB - Poorly differentiated Sertoli-stromal cell tumors and carcinosarcomas of the ovary both show biphasic epithelial and stromal patterns and may both show heterologous stromal elements, presenting a difficult diagnosis. We studied the immunohistochemical profile of Sertoli cell differentiation in human testes and applied these findings to the ovarian tumors. Eleven Sertoli-stromal cell tumors, six carcinosarcomas of the ovary, and 11 testes (six fetal, one infant, and four adult) were studied using antibodies to cytokeratin AE1:AE3 (AE1:3), cytokeratin CAM 5.2 (CAM), epithelial membrane antigen (EMA), vimentin, desmin, muscle specific actin (MSA), S-100 protein (S-100), CA 19-9, CA 125, carcinoembryonic antigen monoclonal (CEA-M), carcinoembryonic antigen polyclonal (CEA-P), and placental alkaline phosphatase (PLAP). In the fetal testes, immature gonadal stroma and sex cord areas stained with vimentin (six of six cases), AE1:3 (five of six cases), and CAM (six of six cases). Sertoli cells in immature gonadal stroma areas, sex cords, and seminiferous tubules of normal fetal, infant, or adult testes never showed immunoreactivity for EMA, S-100, CA 19-9, CA 125, CEA M, CEA-P, or PLAP. All Sertoli-stromal cell tumors stained with AE1:3 and CAM in areas of Sertoli cell differentiation (11 of 11 cases) but did not stain with EMA, PLAP, CEA-P, CEA-M, CA 19-9, CA 125, or S-100 (none of 11 cases). Carcinosarcomas expressed AE1:3 and CAM in all epithelial areas (six of six cases) and most stromal areas (five of six cases). Carcinomatous areas of carcinosarcoma also showed immunoreactivity for EMA (six of six cases), CA 125 (two of six cases), PLAP (two of six cases), CEA-P (two of six cases), and CEA-M (one of six cases), while stromal areas of carcinosarcoma expressed EMA (four of six cases) and S-100 (four of six cases). Heterologous stromal elements were present in three of 11 Sertoli-stromal cell tumors (two showed skeletal muscle and one showed both skeletal muscle and cartilage differentiation) and in four of six carcinosarcomas (one skeletal muscle, one cartilage, and two cartilage and skeletal muscle). All skeletal muscle heterologous elements expressed desmin, vimentin, and MSA. The heterologous cartilage in carcinosarcoma stained with S 100 (three of three), while the one case of heterologous cartilage in Sertoli stromal cell tumor did not. These results suggest that ovarian Sertoli-stromal cell tumor can be distinguished from carcinosarcoma by the absence of staining for EMA, PLAP, CEA, CA 125, or CA 19-9 in epithelial areas of Sertoli-stromal cell tumor.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1612580 TI - Colloid cysts of the third ventricle: immunohistochemical evidence for nonneuroepithelial differentiation. AB - The histogenesis of colloid cysts (CCs) of the third ventricle has been a subject of controversy. We examined, using immunohistochemical techniques, four CCs for the presence of cytokeratins (CKs), glutathione S-transferase isoenzymes (GST-pi, GST-mu), and glial fibrillary acidic protein. Antibodies to both low molecular weight CKs (anti-CK8) and to a mixture of CKs (AE1/AE3) were used. For comparison, normal fetal and adult choroid plexus, ependyma, and nasal mucosa were also examined. The epithelium lining all four CCs showed positive immunostaining for the CKs and GST-pi but not for GST-mu or glial fibrillary acidic protein. Fetal and adult nasal mucosa showed a pattern of immunohistochemical staining almost identical to that of CCs. In contrast, fetal and adult choroid plexus tissue showed positive immunostaining for GST-pi and low molecular weight CKs but not for the CK mixture (AE1/AE3). Fetal and adult ependyma were negative for both CKs and GST-pi. These results suggest that CCs differentiate along nonneural lines distinct from the neuroepithelial differentiation of the choroid plexus and ependyma. PMID- 1612581 TI - Diaphragmatic contraction band necrosis in a perinatal and infantile autopsy population. AB - A morphologic study of the anterolateral costal diaphragm in 125 newborns and infants who died suddenly showed that contraction band necrosis is a common finding. In cases that showed the most extensive lesions, acute asphyxia was the usual mode of death; within eight diagnostic categories birth asphyxia (11 of 26 cases) and sudden infant death syndrome (19 of 30 cases) had the highest frequency of lesions. It was more frequent than myocardial contraction band necrosis and myocardial coagulation necrosis among the cases studied. The morphologic age and, if present, the stage of healing in each case suggested that the diaphragmatic lesion commenced at or shortly before death or at the time of the cardiac arrest that led to death. Thus, the lesion appeared to represent a very early event after a lethal injury, but it had no specificity for the nature of the injury. Because skeletal muscle of the respiratory diaphragm structurally and functionally resembles myocardium, the pathogenesis of contraction band necrosis may be similar in the two muscle types. PMID- 1612582 TI - Transfusion-associated graft-versus-graft and potential graft-versus-host disease in a renal allotransplanted patient. AB - Transfusion-associated graft-versus-host disease (GVHD) is a rare but often fatal condition. We report on a case in which a 54-year-old man with polycystic kidneys shortly after receiving a male cadaver donor kidney developed severe intractable rejection and symptoms of GVHD. In situ hybridization with a Y chromosome- "specific" DNA probe and combined in situ hybridization and immunohistochemistry with monoclonal antibodies defining cellular phenotypes were performed on biopsy and tissue specimens taken at rejection episodes and from the lost allograft. The vast majority of infiltrating leukocytes in the morphologically rejecting kidney parenchyma were of female origin and consisted mainly of T lymphocytes and macrophages. This could only be explained by engraftment of leukocytes received in connection with transfusion of female whole blood in association with the transplantation. The patient developed symptoms of GVHD, and graftectomy was performed due to life-threatening cytomegalovirus infection. This case of combined "graft"-versus-graft disease and GVHD indicates that precautions in the administration of blood transfusion to severely immunosuppressed patients should be taken. We recommend the use of gamma-irradiated and lymphocyte-depleted blood products. PMID- 1612583 TI - Cauda equina tumor with ependymal and paraganglionic differentiation. AB - We describe the case of a 31-year-old woman who was first treated for a pigmented choroid plexus papilloma of the fourth ventricle. Ten year later, she developed a new tumor in the region of the cauda equina. This second neoplasm contained areas of papillary ependymoma that displayed phosphotungstic acid hematoxylin-positive glial fibers and immunoreactivity for glial fibrillary acidic and S-100 proteins. Areas of ependymoma merged with others that displayed the appearance of a paraganglioma, including lobules and nests of chief cells immunoreactive for neuron-specific enolase, synaptophysin, chromogranin, and serotonin. Satellite cells, but not chief cells, stained for glial fibrillary acidic and S-100 proteins. Electron microscopy showed features of both ependymal and paraganglionic differentiation, including intercellular lumina with microvilli, junctional complexes, cell processes with closely packed filaments, and dense core granules. Our case represents a rare example of a cauda equina neoplasm with simultaneous ependymal and paraganglionic differentiation. To our knowledge, this is the first described example of a tumor of this region showing features of both ependymoma and paraganglioma. PMID- 1612584 TI - Radiation-reduced hybrids for the myotonic dystrophy locus. AB - The myotonic dystrophy (DM) gene maps to the long arm of human chromosome 19 and is flanked by markers ERCC1 and D19S51. Also mapping to this region is the polio virus receptor gene (PVS). To produce more markers for this interval, we have constructed radiation-reduced hybrids by selecting for the retention of ERCC1 and for the loss of PVS. One of the cell lines produced has been characterized extensively and contains about 2 Mb of human DNA derived exclusively from chromosome 19, and includes ERCC1 and D19S51. Phage libraries constructed from DNA of this cell line have been screened and several new markers identified, including two for which cDNAs have been isolated. These represent candidate genes for DM. The new markers have also been used to extend the long-range restriction map of this region. PMID- 1612585 TI - Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene. AB - Phenotypic parallels and genetic evidence from comparative mapping suggest that the murine Small eye (Sey) and human aniridia (AN) disorders are homologous. This report describes the isolation of a murine embryonic cDNA that is structurally homologous to the AN cDNA were recently cloned. The murine cDNA detects a 2.7-kb transcript in the adult mouse eye and cerebellum and in human glioblastomas, suggesting a neuroectodermal involvement in the etiology of Sey/AN. Sequence comparison between the murine and the human cDNAs revealed extensive homology in nucleotide sequence (greater than 92%) and virtual identity at the amino acid level. None of the differing amino acids was located within the paired box and homeobox DNA-binding domains. These results provide evidence for a common molecular basis underlying the two genetic disorders and suggest that the Sey system would be an authentic model for human AN. PMID- 1612586 TI - Platelet-derived growth factor A chain: confirmation of localization of PDGFA to chromosome 7p22 and description of an unusual minisatellite. AB - The human PDGFA gene, encoding the A chain of platelet-derived growth factor, has been previously cloned and characterized, but two conflicting chromosomal localizations have been presented. To resolve this controversy, we have now performed nonisotopic in situ hybridization using new genomic PDGFA subclones and analyzed somatic cell hybrid DNAs for the presence of human PDGFA by polymerase chain reaction. The results confirm our previous assignment of PDGFA to chromosome 7p22. New sequence data from the PDGFA locus have been obtained and analyzed. An unusual minisatellite, which includes an evolutionarily conserved protein-coding region of exon 4, was found within IVS4. The minisatellite includes an embedded polymorphic pentanucleotide microsatellite repeat. Analysis of this polymorphism and in situ hybridization both locate PDGFA outside the monosomic region in a patient with a de novo deletion of the short arm of chromosome 7 [del (7)(p22.1-pter)]. PMID- 1612587 TI - Murine chromosomal location of four hepatocyte-enriched transcription factors: HNF-3 alpha, HNF-3 beta, HNF-3 gamma, and HNF-4. AB - The genes for rat hepatocyte nuclear factors 3 and 4 (HNF-3 alpha, HNF-3 beta, HNF-3 gamma, and HNF-4) have been mapped in mouse by analysis of restriction fragment length polymorphisms in interspecific backcross mice. These hepatocyte enriched transcription factors are positive-acting transcription factors with binding sites in regulatory regions of many genes expressed in hepatocytes. Both HNF-3 alpha, beta, and gamma and HNF-4 are also expressed in intestine. They have recently been implicated as potential participants in endodermal development from early gut cells because of their close homology to Drosophila genes, which themselves are expressed in the developing gut. Despite having similar functional roles and highly conserved DNA binding domains, the three loci from the Hnf-3 family of genes mapped to three different mouse chromosomes, suggesting that the Hnf-3 family has become widely dispersed during evolution and implying the necessity for independent activation of each member of the HNF-3 family. PMID- 1612588 TI - A genetic linkage map of 96 loci on the short arm of human chromosome 3. AB - We constructed a genetic map of 96 loci on the short arm of human chromosome 3 (3p) in 59 families provided by the Centre d'Etude du Polymorphisme Humaine (CEPH). Twenty-nine continuously linked loci were placed on the map with likelihood support of at least 1000:1; one locus, D3S213, was placed on the map with likelihood support of 871:1; D3Z1, an alpha satellite centromeric repeat probe, was placed on the map with likelihood support of 159:1; 65 loci were assigned regional locations. The average heterozygosity of the uniquely ordered markers was 49%. The map extends from 3p26, the terminal band of 3p, to the centromere (from D3S211 to D3Z1). Multipoint linkage analysis indicated that the male, female, and sex-averaged maps extend for 102, 147, and 116 cM, respectively. The mean genetic distance between uniquely ordered loci on the sex averaged map was 4.0 cM. Probe density was greatest for the region of 3p between D3F15S2e and the telomere. The sex-averaged map contained two intervals greater than 10 cM. Seventeen probes were localized by fluorescence in situ hybridization. The loci described in this report will be useful in building an integrated genetic and physical map of this chromosome. PMID- 1612589 TI - Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. AB - The chromosomal locations of the human genes NFKB1 and NFKB2, which encode two alternative DNA binding subunits of the NF-kappa B complex, p105 and p49/p100, respectively, have been determined. p105 was assigned to 4q21.1-q24 and p49/p100 to chromosome 10 by Southern blot analysis of panels of human/Chinese hamster cell hybrids. The locations were confirmed by fluorescence in situ hybridization and mapped with greater resolution to 4q23 and 10q24, respectively. These results demonstrate that these members of the NF-kappa B family are unlinked. Interestingly, p49/p100 as well as p105 maps to regions associated with certain types of acute lymphoblastic leukemia. PMID- 1612590 TI - Structure and evolution of the human prosaposin chromosomal gene. AB - The gene for prosaposin was characterized by sequence analysis of chromosomal DNA to gain insight into the evolution of this locus that encodes four highly conserved sphingolipid activator proteins or saposins. The 13 exons ranged in size from 57 to 1200 bp, while the introns were from 91 to 3812 bp in length. The regions encoding saposins A, B, and D each had three exons, while that for saposin C had only two. This sequence included the regions that encode the carboxy terminus of the signal peptide, the four mature prosaposin proteins, and the 3' untranslated region. Primer extension studies indicated that over 99% of the coding sequence was contained in these 19,985 bp. Use of PCR and reverse PCR techniques indicated that the most 5' coding approximately 140 bp contained large introns and at least two small exons. Analyses of the intronic positions in the saposin regions indicated that this gene evolved from an ancestral gene by two duplication events and at least one gene rearrangement involving a double crossover after introns had been inserted into the gene. PMID- 1612591 TI - The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions. AB - The six members of the human prothymosin alpha gene family have been cloned and sequenced. One gene (PTMA) contains introns and appears to be the source of all isolated prothymosin alpha cDNAs. The remaining five genes are processed pseudogenes. Four of them have consensus TATA elements upstream of sequences nearly identical to the transcriptional start region of the intron-containing gene. Those four genes also contain open reading frames coding for proteins closely related to prothymosin alpha. In two of the pseudogenes, PTMAP2 and 5, the encoded proteins differ from the product of the parental gene at only two and four locations, respectively. The fifth pseudogene (PTMAP1) encodes a different protein owing to an upstream translational initiation start site and multiple deletions and insertions. Because the potential for expression exists in this system, a search for pseudogenomic transcripts was undertaken using the polymerase chain reaction to amplify reverse transcripts of mRNAs from many human tissues and bulk DNA from several human cDNA libraries. Evidence for pseudogenomic transcripts was not obtained. Therefore, we conclude that the human prothymosin alpha gene family contains only one functional gene. PMID- 1612592 TI - Chromosome 16-specific repetitive DNA sequences that map to chromosomal regions known to undergo breakage/rearrangement in leukemia cells. AB - Human chromosome 16-specific low-abundance repetitive (CH16LAR) DNA sequences have been identified during the course of constructing a physical map of this chromosome. At least three CH16LAR sequences exist and they are interspersed, in small clusters, over four regions that constitute more than 5% of the chromosome. CH16LAR sequences were observed in one unusually large cosmid contig (number 55), where the ordering of clones was difficult because these sequences led to false overlaps between noncontiguous clones. Contig 55 contains 78 clones, or approximately 2% of all the clones contained within the present cosmid contig physical map. Fluorescent in situ hybridization of multiple clones, including cosmid and YAC contig 55 clones, mapped the four CH16LAR-rich regions to bands p13, p12, p11, and q22. These regions are of biological interest since the pericentric inversion and the interhomologue translocation breakpoints commonly found in acute nonlymphocytic leukemia (ANLL) subtype M4 fall within these bands. Sequence analysis of a 2.2-kb HindIII fragment from a cosmid containing a CH16LAR sequence indicated that one of the CH16LAR elements is similar to a minisatellite sequence in that the core repeat is only 40 bp in length. Additional characterization of other repetitive elements is in progress. PMID- 1612593 TI - Microdissection of human chromosomal regions 8q23.3-q24.11 and 2q33-qter: construction of DNA libraries and isolation of their clones. AB - Human chromosomal regions 8q23.3-q24.11 and 2q33-qter were microdissected, DNAs from the regions were amplified with the primer-linker method of polymerase chain reaction (PCR), and their DNA libraries were constructed by cloning into pUC19. The primer-linker PCR involved Sau3AI digestion of microdissected chromosomal DNAs, ligation of the digests to a 10mer DNA linker and 24mer primer, filling the recessed 3' ends, and PCR amplification using the 24mer DNA as a primer. A total of 3.5 x 10(4) pUC19 recombinants (8q library) from the 8q region and 5.0 x 10(4) pUC clones (2q library) from the 2q region were obtained. From the 8q library, 60 pUC clones were selected, while 88 pUC-clones were selected from the 2q library. These clones were Southern blot analyzed on hybrid cell panels with or without human chromosome 8 or 2. Twelve (20%) of the 60 8q-derived clones were unique DNA sequences, and 9 were subjected to deletion analysis in the genomic DNA of two patients, one with trichorhino-phalangeal syndrome (TRPS) type I and the other with TRPS type II, both with del(8) (q23.3q24.13). Five of the 9 pUC clones tested showed a one-copy density in both patients, an indication that the clones map to the region deleted in both patients. Screening a genomic DNA library constructed in the phage revealed a clone with a 9.4-kb insert and a one-copy density in both patients. From the 2q library, 15 (17%) of the 88 pUC clones obtained were unique sequences. When a phage library was screened, 8 clones were obtained: 4 were identical and 2 were overlapping sequences.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612594 TI - Fluorescent in situ identification of human marker chromosomes using flow sorting and Alu element-mediated PCR. AB - A novel approach to the identification of human chromosomes has been developed. Chromosomal in situ hybridization (or "chromosome painting") has been performed using Alu element-mediated PCR products from small quantities (250-500) of flow sorted normal and abnormal chromosomes. Chromosome paints for various normal chromosomes, including 5, 6, 7, 14, 18, 19, 21, and 22, were generated and shown to be effective in the identification of the appropriate chromosomes. In addition, certain abnormal chromosomes, including a mental retardation-associated deletion chromosome 11 (q22-q23), the products of the constitutional translocation t(11;22), and the CML-associated t(9;22), were used to generate region-specific paints. In each case, the appropriate regions of the chromosomes were highlighted and this strategy is, therefore, well suited to the identification of previously unidentified marker chromosomes. A further direct consequence of this work is that chromosome paints specific for the common aberrant chromosomes, such as the Philadelphia chromosome, can be generated and made widely available. These may find particular use in the analysis of complex or masked chromosomal translocations. PMID- 1612595 TI - A human moderately repeated Y-specific DNA sequence is evolutionarily conserved in the Y chromosome of the great apes. AB - Evolutionary conservation of the human-derived moderately repeated Y-specific DNA sequence Y-190 (DYZ5) was investigated in the chimpanzee, orangutan, and gorilla. Southern blot analysis showed the presence of the sequence in the Y chromosome of all great apes. Pulsed-field gel electrophoresis and in situ hybridization revealed that the repeat is organized in one major block and confined to a small region of the Y chromosome of the three species. DYZ5 was assigned to the proximal short arm of the Y chromosome of the chimpanzee and orangutan and to the long arm of the Y chromosome of the gorilla. In light of its evolutionary conservation, DYZ5 may have an as yet undetermined structural function in the Y chromosome. PMID- 1612596 TI - Baboon apolipoprotein C-I: cDNA and gene structure and evolution. AB - We have isolated and characterized cDNA and genomic clones for apolipoprotein C-I (apoC-I) encoded by the APOC1 locus in baboons. Baboon apoC-I cDNA is only 410 bp in size, but the gene spans 4.5 kb including four small exons and three introns containing a large number of Alu repeats. The coding sequences of apoC-I cDNA and genomic clones are identical, indicating that this genomic clone contains the functional gene for apoC-I rather than a pseudogene like human APOC1'. We also detected a second gene in Southern blots of baboon genomic DNA that may correspond to the human APOC1' pseudogene. Two start sites for baboon APOC1 transcription were mapped to nucleotides that are 7 and 9 bp downstream from the predominant start site for human APOC1 transcription. Alignment of Alu repeats showed that the 5' region of the baboon APOC1 gene is more similar to that of the human pseudogene APOC1', and the 3' region and coding sequences are more similar to those of human APOC1. These regions are separated by an Alu repeat that is present only in the baboon gene, perhaps reflecting its role in gene rearrangement or conversion. Sequence comparisons from baboon, human, dog, and rat showed extensive differences in apoC-I amino acid sequences, which are less conserved than nucleotide sequences. However, comparisons of hydrophilicity profiles show significant conservation of protein domains that may be important for apoC-I function. PMID- 1612597 TI - Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene. AB - We tested the use of a modified method of single-strand conformational polymorphism (SSCP) analysis for the detection of point mutations in the human ornithine-delta-aminotransferase gene. Using a combination of three different electrophoretic conditions, we detected 20/20 known mutations. In a prospective study of 24 previously uncharacterized mutant OAT genes, we found 13 different mutations accounting for 19 (79%) of the 24. We conclude that SSCP is an efficient technique with high sensitivity and specificity. PMID- 1612598 TI - Rapid isolation of cosmids from defined subregions by differential Alu-PCR hybridization on chromosome 22-specific library. AB - A method based on the differential screening of a chromosome-specific cosmid library with amplified inter-Alu sequences obtained from a set of somatic cell hybrids has been developed to target the isolation of probes from predefined subchromosomal regions. As a model system, we have used a chromosome 22-specific cosmid library and four cell hybrids containing different parts of this chromosome. The procedure has identified cosmids that demonstrate differential hybridization signals with Alu-PCR products from these cell hybrids. We show, by in situ hybridization or individual mapping, that their hybridization pattern is indicative of their sublocalization on chromosome 22, thus resulting in a large enrichment factor for the isolation of probes from specific small chromosome subregions. Depending on the local Alu-sequence density, from 3 to 10 independent loci per megabase of genome can thus be identified. PMID- 1612599 TI - Isolation and characterisation of (AC)n microsatellite genetic markers from human chromosome 16. AB - A cosmid library of human chromosome 16 has been subcloned, and (AC)n microsatellite positive clones have been identified and sequenced. Oligonucleotide primers flanking the repeat were designed and synthesized for (AC)n microsatellites with n greater than 16. These microsatellite loci were then mapped by PCR using a somatic cell hybrid panel of human chromosome 16, and their heterozygosities and allele frequencies determined. Fourteen (AC)n microsatellites were mapped to discrete physical intervals of human chromosome 16 defined by a mouse/human hybrid panel. Nine of these have expected heterozygosities ranging between 0.60 and 0.79, four have expected heterozygosities between 0.02 and 0.49, and one detected three loci where the alleles could not be resolved. PMID- 1612600 TI - Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19. AB - The genes encoding receptors for the chemotactic ligands C5a (C5AR) and FMLP (FPR) were mapped using a panel of somatic cell hybrids to chromosome 19. Because the hybridization pattern on Southern analysis suggested an intron structure or related genes in the case of FPR, genomic clones were characterized. Two structural homologues of the FMLP receptor, clones 81 (FPRH1) and 82 (FPRH2), were identified, which similarly map to chromosome 19. The structural homologues do not recognize the ligand FMLP, but are likely chemotactic receptors. PMID- 1612601 TI - Dideoxy fingerprinting (ddE): a rapid and efficient screen for the presence of mutations. AB - We describe dideoxy fingerprinting (ddF), a hybrid between dideoxy sequencing and SSCP that can detect the presence of single base and other sequence changes in PCR-amplified segments. As implemented herein, ddF involves a Sanger sequencing reaction with one dideoxynucleotide followed by nondenaturing gel electrophoresis. When ddF was used to examine segments of the human factor IX gene, 84 of 84 different mutations were detected with a very low rate of false positive signals. The approximate locations of the sequence changes could be determined from the ddF pattern and samples with different sequence changes had different fingerprints. In addition, large segments could be amplified and rapidly screened by ddF in multiple smaller subsegments. The patterns observed with ddF are instructive in that they suggest an inherent limitation in the detection of certain mutations by SSCP. PMID- 1612602 TI - Localization of the Mas proto-oncogene to a densely marked region of mouse chromosome 17 associated with genomic imprinting. AB - The mouse homolog of the human proto-oncogene MAS was mapped by two interspecific backcrosses to the proximal portion of MMU17. Higher resolution mapping was accomplished through the analysis of genotypes duplicated or deleted for a megabase-size subregion within MMU17. The results demonstrate a map position for Mas in the close vicinity of Igf2r, which encodes another membrane receptor known to undergo genomic imprinting. The data provide further evidence for the clustering of genes in a 1-Mb region of chromosome 17, with the absence of any identified genes in a nearby region likely to be six times larger. PMID- 1612603 TI - Linkage mapping of the carbonyl reductase (CBR) gene on human chromosome 21 using a DNA polymorphism in the 3' untranslated region. AB - A DNA polymorphism has been found in the 3' untranslated region of the carbonyl reductase gene (CBR). Genotypes of the members of the CEPH pedigrees have been obtained and used in linkage analysis to map the CBR gene in the linkage map of human chromosome 21. The gene maps between the interferon-alpha receptor (IFNAR) and the D21S55 loci. PMID- 1612604 TI - Mapping and characterization of a novel human myc-like (MYCLK1) sequence. AB - The myc family of proto-oncogenes consists of several members that possess regions of sequence homology and some have known similarities in structure and function. We have isolated an 8.8-kb EcoRI fragment from a human genomic library by hybridization to a 28-base oligonucleotide probe derived from a region of the second exon of MYC, which is highly conserved in the myc gene family. Sequence analysis of this myc-like (MYCLK1) DNA fragment has revealed the existence of a region with 85% homology to the 28-base oligonucleotide probe. An open reading frame of 207 nucleotides containing the region of homology was found. We have mapped MYCLK1 to human chromosome 7 at band p15 by chromosome in situ hybridization; this site is distinct from the map location of previously characterized myc genes. Whether MYCLK1 represents a new functional member of the myc family of proto-oncogenes remains to be determined. PMID- 1612605 TI - Fluorescence in situ hybridization establishes the order cen-DXS28(C7)-DXS67(B24) DXS68(L1)-tel in human chromosome Xp21.3. AB - We report here on the order of three DNA markers, C7, B24, and L1, based on the arrangement of their fluorescently labeled hybridization sites in interphase cell nuclei. The three markers map distal to the Duchenne muscular dystrophy (DMD), glycerol kinase deficiency (GKD), and adrenal hypoplasia (AHC) loci on human chromosome Xp21.3. Their order has been a matter of controversy. In interphase chromatin, B24 maps between C7 and L1. We estimate from interphase distance that C7 and L1 are 300-500 kb apart. When the three markers are hybridized to interphase cells of Nijmegen1, a patient with DMD, GKD, and AHC, only C7 appears to be deleted, rather than both C7 and L1, as had been reported elsewhere. C7 is also the only one of the three markers deleted in several other DMD patients studied by others. The deletion results indicate that C7 is the most proximal of the three markers and allow the trio of ordered probes to be oriented on the chromosome: cen-C7(DXS28)-B24(DXS67)-L1(DXS68)-tel. PMID- 1612606 TI - Banding profiles of LTR of human endogenous retrovirus HERV-A in 24 chromosomes in somatic cell hybrids. AB - The human genome carries multiple copies of sequences related to endogenous retroviral genomes. We investigated the distribution of one of these sequences, HERV-A, in 24 human chromosomes by Southern analyses using DNAs from flow-sorted chromosomes or rodent cells carrying a single human chromosome. The results showed that HERV-A is distributed among all human chromosomes and that each chromosome has a specific Southern blot profile. The chromosome-specific pattern did not show significant polymorphism, except in a few cases, when the same chromosome obtained from different individuals was compared. These chromosome specific Southern hybridization profiles may be useful for chromosome karyotyping. This would allow the integrity of human chromosomes in human-rodent somatic cell hybrids to be monitored without using conventional cytogenetic methods. PMID- 1612607 TI - A human aldehyde dehydrogenase (aldose reductase) pseudogene: nucleotide sequence analysis and assignment to chromosome 3. AB - Four cosmid clones containing putative pseudogenes for human aldehyde dehydrogenase (Aldose reductase) were isolated from libraries made to two individuals. These clones show different patterns on digestion with restriction endonucleases and probably represent distinct and separate loci. The DNA sequence of one of the putative pseudogenes (cosmid AR.F) was determined, and comparisons demonstrate 89.7% homology with the cDNA sequence of the functional aldose reductase gene. This pseudogene sequence contains no intronic sequences, whereas the functional aldose reductase has nine introns. In addition, the homology disappears in region 5' to the transcription start site for the cDNA, implying that regulatory elements such as the promoter are missing from this pseudogene. The pseudogene defined by cosmid AR.F has been mapped to chromosome 3 by polymerase chain reaction using amplimers specific for this pseudogene to amplify DNA from somatic cell hybrids. PMID- 1612608 TI - Human dopa decarboxylase: localization to human chromosome 7p11 and characterization of hepatic cDNAs. AB - We have cloned full-length DDC cDNAs from a human hepatoma cDNA library [DDC; dopa decarboxylase; aromatic-L-amino acid decarboxylase, EC 4.1.1.28]. The protein encoded by hepatoma cells is the same as that encoded by adrenal chromaffin derived pheochromocytoma cells, despite reported differences in biochemical properties. We have confirmed the location of the DDC gene to chromosome 7 using a new panel of somatic cell hybrids, and we have localized the gene to band p11 on chromosome 7 by fluorescent in situ hybridization. The human gene retains 65% amino acid identity with Drosophila DDC (Accession No. X04426) and considerable structural similarity with other enzymes (F.R. Jackson, 1990, J. Mol. Evol. 31:325-329, and references therein). PMID- 1612609 TI - Fine mapping of the human biglycan (BGN) gene within the Xq28 region employing a hybrid cell panel. AB - Human biglycan is a small proteoglycan that is expressed at high levels in the growing skeleton and in human skin at the cell surface of differentiating keratinocytes. The human gene for biglycan (BGN) has previously been mapped by in situ hybridization to the Xq27-q28 region. Employing somatic hybrid cell lines with human X chromosome breakpoints within this region, we performed a fine mapping of the gene within Xq28. Our results indicate that the biglycan gene is proximal to the red/green cone pigment genes, G6PD, and coagulation factor VIII and is distal to DXS304, DXS305, and GABRA3. The biglycan gene precisely maps to a region of the X chromosome, where, by comparative gene mapping, one would expect to find the gene for X-linked dominant chondrodysplasia punctata/ichthyosis/short stature (Happle) syndrome. Hence, BGN is a candidate gene for the Happle syndrome. PMID- 1612610 TI - The human gene (DSG2) coding for HDGC, a second member of the desmoglein subfamily of the desmosomal cadherins, is, like DSG1 coding for desmoglein DGI, assigned to chromosome 18. AB - Desmoglein is a transmembrane glycoprotein of the cadherin superfamily present in the desmosomal junction in vertebrate epithelial cells. At least two variants of desmoglein are differentially expressed in human tissues: DGI, a characteristic desmosomal protein; and HDGC, which is, for example, expressed in the simple epithelium of the colon. Using a PCR assay, we were able to assign DSG2, the gene coding for desmoglein HDGC, to chromosome 18, the same chromosomal localization to which we have previously assigned DSG1 coding for desmoglein DGI. PMID- 1612611 TI - Assignment of the homolog of the MAS1 oncogene to mouse chromosome 17. PMID- 1612612 TI - Assignment of the human recombination activating gene 1 (RAG1) to the 14q21.3 q22.2 region. PMID- 1612614 TI - An experimental system for auditory image representations. AB - This paper presents an experimental system for the conversion of images into sound patterns. The system was designed to provide auditory image representations within some of the known limitations of the human hearing system, possibly as a step towards the development of a vision substitution device for the blind. The application of an invertible (1-to-1) image-to-sound mapping ensures the preservation of visual information. The system implementation involves a pipelined special purpose computer connected to a standard television camera. The time-multiplexed sound representations, resulting from a real-time image-to-sound conversion, represent images up to a resolution of 64 x 64 pixels with 16 gray tones per pixel. A novel design and the use of standard components have made for a low-cost portable prototype conversion system having a power dissipation suitable for battery operation. Computerized sampling of the system output and subsequent calculation of the approximate inverse (sound-to-image) mapping provided the first convincing experimental evidence for the preservation of visual information in the sound representations of complicated images. However, the actual resolution obtainable with human perception of these sound representations remains to be evaluated. PMID- 1612613 TI - A muscle fatigue index based on the relationship between preceding background activity and myotatic reflex response (MRR). AB - A new index of muscular fatigue was developed using the myotatic reflex response (MRR). The MRR of masseter muscles is evoked by periodical mechanical chin tapping during clenching. The MRR waveform is composed of somewhat synchronized action potentials of muscle fibers. We estimate the change of the MRR waveform due to fatigue using the instantaneous frequency pattern (IFP) with the Hilbert transform. As a result, the features of IFP were different from the monotonic changes that have been observed by the conventional fatigue indices. That is, a plateau IFP was observed ahead of considerable fatigue, whereas the IFP showed a monopeak pattern during other phase of an exercise. Also, the relationship between the preceding background mean power frequency and the instantaneous frequency around the first part of the MRR waveform was nonlinear during the whole process of fatigue. These features may allow us to estimate the degree of fatigue at each time instant. Although the details have not yet been solved, by using the computer simulations one of them seemed to be the alteration of the dominant frequency components. The dominant frequency components may be related to the active muscle fiber types. PMID- 1612615 TI - Simulation of multipolar fiber selective neural stimulation using intrafascicular electrodes. AB - A realistic, quantitative model is presented for the excitation of myelinated nerve fibers by intrafascicular electrodes. It predicts the stimulatory regions of any configuration of any number of electrodes, positioned anywhere inside the fascicle. The model has two parts. First, the nerve fiber is represented by a lumped electrical network and its response to an arbitrary extracellular potential field is calculated. Second, assuming a cylindrical geometry of the nerve bundle and its surroundings, an analytical expression for this field is derived. With realistic parameters, the model is applied to two cases: monopolar stimulation by a single cathode and stimulation by a specific tripolar configuration. It is shown that tripolar stimulation has the better spatial selectivity. Also tripolar stimulation is less sensitive to the conductivity of the medium surrounding the nerve and yields a more natural recruitment order. PMID- 1612616 TI - Quantitative analysis of associated and disassociated phorias: linear and nonlinear static models. AB - Ogle proposed two measures of oculomotor balance, called associated and disassociated phorias, which he assumed were equivalent. However, experimentally determined values of these phorias do not show a close correspondence. To analyze the rationale behind Ogle's assumption of equality, a linear static model was evaluated. It was found that indeed the linear model predicts an exact correspondence between associated and disassociated phorias. Thus, his assumption depended on the presence of a linear model. To account for the discrepancy between these two measures, a nonlinear static model, containing the dead space operators depth of field and Panum's fusional area, was evaluated. Four equations for fixation disparity were derived corresponding to the four combinations of deadspace operator outputs. It was found that only one of these four equally possible solutions for associated phoria corresponded to the disassociated phoria. This suggests that the variability in the four solutions may account for the scatter in the experimental data. The nonlinear model was analyzed further to determine its sensitivity to parameter changes and to show how such a model could generate the classical shape of the fixation disparity curve. PMID- 1612617 TI - Electric-field distribution near rectangular microstrip radiators for hyperthermia heating: theory versus experiment in water. AB - A rectangular microstrip antenna radiator is investigated for its near-zone radiation characteristics in water. Calculations of a cavity model theory are compared with the electric-field measurements of a miniature nonperturbing diode dipole E-field probe whose 3 mm tip was positioned by an automatic three-axis scanning system. These comparisons have implications for the use of microstrip antennas in a multielement microwave hyperthermia applicator. Half-wavelength rectangular microstrip patches were designed to radiate in water at 915 MHz. Both low (epsilon r = 10) and high (epsilon r = 85) dielectric constant substrates were tested. Normal and tangential components of the near-zone radiated electric field were discriminated by appropriate orientation of the E-field probe. Low normal to transverse electric-field ratios at 3.0 cm depth indicate that the radiators may be useful for hyperthermia heating with an intervening water bolus. Electric-field pattern addition from a three-element linear array of these elements in water indicates that phase and amplitude adjustment can achieve some limited control over the distribution of radiated power. PMID- 1612618 TI - Computation of the potential distribution in a four-layer anisotropic concentric spherical volume conductor. AB - A method for solving the potential distribution in a multilayer anisotropic concentric spherical volume conductor, which has recently been described in the literature, has been tested and found to be numerically unstable. In this paper it is demonstrated how these numerical difficulties can be avoided. Moreover, the method is extended by lifting the previously imposed restriction on the innermost region to be isotropic. A convergence criterion for determining the required number of terms in the final series expansion is proposed. The influences of radial and tangential conductivity values of the skull and brain tissue on the dipole-induced potential are investigated. PMID- 1612619 TI - Some imaging parameters of the oblique dipole layer cardiac generator derivable from body surface electrical potentials. AB - The goal of noninvasively imaging the cardiac electrical generator is considerably complicated by the conductive anistropy of the cardiac muscle which, as featured in the oblique dipole layer model of ventricular depolarization, introduces muscle fiber geometry and a conductivity tensor as additional unknowns. The ventricular surface activation map has been previously presented as a description of the cardiac generator in image form, but the integral equation defining its relationship to the body surface potentials is valid only under the less accurate uniform dipole layer hypothesis. Using an argument from differential geometry, which allows the integral equation approach to be bypassed, we show that the critical points of this map can still be localized on the heart surface from the body surface potentials in a manner fully consistent with the oblique dipole layer model. Thus, in principle, a realistic and useful "image-like" output is possible in a limited way even without explicit information regarding conductivity anisotropy. The realization of this output will require improvements in the temporal resolution presently available from existing body surface potential mapping systems. PMID- 1612620 TI - An information flow technique for category related evoked potentials. AB - We report a technique for studying interactions among many subsystems of a biological system. A general mathematical technique is developed for information flow among various subsystems of a system when two or more classes of stimuli are presented to the system. The technique is validated by various simulation studies and then applied to a brain system. The usefulness of the technique is demonstrated for visual event related potentials (ERP's) obtained from human subjects suffering from phobias. The stimuli are briefly flashed words and phrases. The word classes are pleasant, unpleasant, conscious, and unconscious. The conscious class consists of words known by the patient to relate to the problem, whereas the unconscious class of words consists of words related to deep conflicts which are not recognized by the patient. It is demonstrated that information flow is suppressed under supraliminal presentation of the unconscious class, but is strong under subliminal presentation. The technique has the potential of being an objective indicator of conflictual relationships in these patients. The principle of the technique can be applied to any system in which interactions among subsystems are to be analyzed. PMID- 1612621 TI - Application of adaptive filters to noninvasive acoustical detection of coronary occlusions before and after angioplasty. AB - Previous studies have indicated that coronary stenoses produce sounds due to the turbulent blood flow in these vessels [1]-[10]. Measurement of these signals forms the basis of our noninvasive approach to the detection of coronary artery disease. It is during diastole that coronary blood flow is maximum and the sounds associated with turbulent blood flow through partially occluded coronary arteries would be loudest [1]-[10]. Isolated diastolic heart sounds taken from recordings made at the patient's bedside were modeled using the autoregressive (AR) and autoregressive moving average (ARMA) methods [4], [7] after adaptive line enhancement (ALE). Decisions were made in a blind fashion without prior knowledge of whether a given recording was made before or after angioplasty. Resulting model frequency spectra showed greater high-frequency components (between 400 and 800 Hz) in preangioplasty patients, and a consistent shift in amplitude of the second pole pairs of the AR and ARMA methods with surgery. Blind assessment, based on frequency spectra and poles, correctly classified the diastolic recordings in 18 of 20 cases. These results provide strong evidence supporting our hypothesis that coronary stenoses produce detectable sounds during diastole [1]-[10]. PMID- 1612622 TI - Development of a medical fiber-optic oxygen sensor based on optical absorption change. AB - A new fiber-optic oxygen sensor has been developed for use in medical applications. The sensor's viologen indicator becomes strongly absorbent after brief UV stimulation, and then returns to the transparent state. The rate of indicator return to transparency is proportional to the local oxygen concentration. Indicator absorbance is monitored with a red LED and receiving photodiode, and absorbance data are processed by a dedicated cpu. The solid-state sensor system has performance comparable to existing oxygen measurement techniques, and may be applicable for both in vitro and in vivo oxygen measurements. PMID- 1612623 TI - The relationship of surface reflectance measurements to optical properties of layered biological media. AB - Reflectance from a turbid biological tissue is discussed for a diffusive light source illuminating the surface of the medium, and is related to the optical property distribution within the medium and to photon propagation through the medium. A three-dimensional photon diffusion model with closed form is developed to describe the photon diffuse intensity in a homogeneous medium. The solution is extended by numerical methods to the medium with layered structure. The concepts of photon flux paths and of reflectance indexes are utilized, together with reflectance data, to extract information about the internal optical properties of a medium. The flux path concept was corroborated by successfully detecting in vivo and ex vivo layered differences in optical properties within the biological medium. These studies suggest that the optical properties of subdermal tissue can be measured from light reflectance and that the effect of the upper skin layers can be eliminated. PMID- 1612624 TI - Temperature selective deposition of Parylene-C. AB - A new method for selectively depositing conformal, biocompatible coatings of Parylene-C on implantable integrated circuit structures is described. The technique consists of using thin film or diffused resistors to electrically heat the area where an opening in the Parylene is desired. Theoretically predicted and actual Parylene-C thickness are compared. PMID- 1612625 TI - [Atypical mycobacterial infections]. PMID- 1612626 TI - [Clinical atypical mycobacterial infections]. AB - In adults atypical mycobacteria usually cause pulmonary disease, lymphadenitis in children and disseminated disease in the course of the acquired immunodeficiency syndrome. Apart from that atypical mycobacteria lead to cutaneous lesions as well as to local abscess formation and necrotic tissue lesions following accidental or iatrogenic trauma of the skin or the soft tissues. Whereas well-established and upcoming microbiologic procedures easily allow an exact classification of the organism, clinical diagnosis is sometimes problematic. PMID- 1612627 TI - [Microbial diagnosis of atypical mycobacteria]. AB - The introduction of the radiometric system in the diagnostic of tuberculosis caused an increase of positive specimens and shortened the time of detection markedly. This is true for strains of tuberculosis complex and especially atypical mycobacteria. The majority of these is highly resistant to drugs. Therefore, the conventional method of susceptibility tests gives no relevant results for therapy. These are obtained when combinations of drugs are tested. The most important character of atypical mycobacteria is optional pathogenicity. This is why one has to decide for each isolation whether an infection has to be assumed or a colonization only. Atypical mycobacteria are present in the environment of men and are able to multiply under unfavourable conditions. Therefore, they are a potential hazard for men. PMID- 1612628 TI - [Current therapy of atypical mycobacterial infections]. AB - Therapeutic possibilities as well as efficacy of chemotherapy in diseases caused by the 12 major species of potentially pathogenic Mycobacteria nontuberculosis are discussed. As opposed to M. tuberculosis, M. nontuberculosis share a reduced sensitivity towards a number of antibiotic and antitubercular agents, which, however, differs in terms of specificity. The resulting therapeutical problems as well as the various manifestations, which quite often present a limitation themselves, necessitate treatment indications regarding extent of disease, prognosis and course of the usually present, underlying disease. Due to the introduction of a new macrolide generation, e.g., clarithromycine, azithromycine, but also due to greater experience with quinolones, first success in treatment has been achieved in infections known to be difficult to treat (e.g., M. avium infections in AIDS patients). However, in order to avoid the development of resistant strains, and due to the frequently found synergisms in vitro, nearly all infections should be treated by means of combined chemotherapy. In infections difficult to treat, e.g., M. ulcerans, M. scrofulaceum, M. fortuitum/chelonei, surgical cleaning-up, or reduction of pathogens, is still of importance. PMID- 1612629 TI - [Microbiological diagnosis of Legionnaires' disease]. AB - Besides other bacterial genera legionellae are a major causative agent of severe pneumonia. Therefore, it is essential to include legionnaires' disease into the diagnostics of pneumonia of unknown origin. The appreciable number of different species and serogroups of legionellaceae, most of them pathogenic for humans, render this task more difficult. The cultural isolation of legionellae from patient or environmental samples is easily performed, the identification of the isolates may be difficult, however. Structural features of the bacteria as determined by biochemical techniques may support the usual immunological identification. Now as before the serological determination of the patients' antibody production as well as the direct detection of bacteria by immunofluorescence microscopy are basic diagnostic procedures. In addition, it is possible to test for legionella antigens excreted in patients' urines; the diagnostic value of this assay, however, is dependent on the manufacturer of the system. As well the clinical diagnostic efficiency of a commercial nucleic acid probe has been questioned sometimes. In the future the polymerase chain reaction may prove as a valuable diagnostic tool but the ubiquity of legionellae in aquatic habitats requires a very critical evaluation of this high-sensitivity method. PMID- 1612630 TI - [Diagnosis of chlamydia and mycoplasma infections of the respiratory tract]. AB - Chlamydia- and mycoplasma diseases are nowadays still confirmed by serology. Since during the acute phase the serological results are often negative, the conformation of an atypical pneumonia due to M. pneumoniae or chlamydia species must be based on more rapid tests, i.e. direct antigen or hybridisation approaches. PMID- 1612631 TI - [Rapidity versus reliability: a critical analysis of the rapid diagnosis of mycobacterial infections with the polymerase chain reaction (PCR)]. AB - In this contribution we analyzed the reliability and the diagnostic value of the results obtained by direct amplification of mycobacterial DNA from patient specimens. Presently, the PCR-method is not as sensitive as recommended culture techniques. In cases of low concentration of mycobacteria in specimens (microscopic negative!) false-negative PCR-results are not rare. PMID- 1612632 TI - [Complement receptor 3 deficiency in systematic lupus erythematosus]. AB - A defect of a functional epitope of the complement receptor 3 is described in a patient with SLE and immune vasculitis. This defect interferes with the interaction of CR3 with its ligand C3bi. PMID- 1612633 TI - [Coincidence of a primary sclerosing cholangitis with an undifferentiated autoimmune disease]. AB - Primary sclerosing cholangitis is described in a 19-year-old woman suffering from undifferentiated autoimmune disease with polyserositis, monarthritis, positive anti-nuclear antibodies and anti-myeloperoxidase antibodies, Coombs-test-positive anaemia and hypogonadotropic hypogonadism. PMID- 1612634 TI - Role of lipoxins A4 and B4 in the generation of arachidonic acid metabolites by rat mast cells and their effect on [3H]serotonin release. AB - Basophils located in tissues are called mast cells and are found in connective tissue. Many different compounds are secreted from basophil granules upon appropriate stimulation. Products such as heparin, histamine, serotonin (5 hydroxytryptamine, 5-HT), and membrane-derived materials which give rise to arachidonic acid metabolites, such as prostaglandins and leukotrienes, are some of the more important compounds released by mast cells. These compounds, when released after stimulation with a variety of molecules, such as IgE, specific antigen anaphylotoxin, as well as the compound 48/80 (C48/80) or calcium ionophore A23187, cause contraction of endothelial cells and mediate atopic or anaphylactic hypersensitivity. In this report, we study the generation of some arachidonic acid products, namely leukotrienes C4, D4, E4, and B4 and the prostaglandins D2 and E2 by rat peritoneal mast cells (RPMC), using calcium ionophore A23187 as a degranulating agonist. We have also studied the new lipoxygenase products, lipoxins A4 and B4, on RPMC secretion using C48/80 as a secretagogue. A rat basophilic leukemia cell line (RBL) was also used to compare results with RPMC. In this paper we have demonstrated that RPMC stimulated with A23187 release LTC4, LTD4, LTE4 and LTB4 and also PGD2 but not PGE2. These results were also confirmed when RBLs were used. In addition, we have shown that mast cells pretreated with LTC4, LTD4, LTE4 or 15-HETE do not modify the release of [3H]5HT exerted by C48/80 (0.5 microgram/ml) or A23187 (5 micrograms/ml). When LXA4 or B4 was used, mast cells were inhibited slightly (not statistically significant) from degranulating after the secretagogue treatment.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612635 TI - Serum kynurenine and neopterin concentrations in patients with cardiomyopathy. AB - Serum kynurenine and neopterin concentrations were determined in patients with hypertrophic (n = 22) and dilated (n = 23) cardiomyopathy. Significantly increased kynurenine and neopterin levels have been observed in cases of dilated cardiomyopathy. In these patients we found a positive correlation between serum kynurenine and neopterin levels (RS = 0.52, P less than 0.001). There existed several associations between the laboratory parameters neopterin and kynurenine and clinical findings, such as left ventricle (LV) systolic volume and LV circumferential fiber shortening velocity in patients with dilated cardiomyopathy (all P less than 0.05). In vitro, interferon-gamma induces the formation of neopterin in human monocytes/macrophages. Also the degradation of tryptophan via the kynurenine pathway is induced by interferon-gamma. Our data show that increased kynurenine as well as neopterin accumulation in serum are associated with severity of dilated cardiomyopathy. Thus, the data point to a role of immune activation in the pathogenesis of the disease. PMID- 1612636 TI - Lipid and protein components of the syncytiotrophoblast plasma membrane inhibit lymphocyte proliferation by two distinct pathways. AB - The ability of syncytiotrophoblast plasma membrane lipid and protein fractions (STPM lipids, STPM proteins), tested under a reconstituted form, to inhibit lymphocyte proliferation induced by PHA was investigated. The cytostatic activity of STPM proteins appeared greater than that of the STPM lipids. Furthermore, IL-2 production and IL-2 receptor expression by activated lymphocytes were markedly decreased in the presence of STPM proteins compared to the native membrane but remained unaffected in the presence of STPM lipids. Finally, the inhibition of lymphoproliferation could be maintained after removal of the protein fraction from lymphocytes prior to stimulation by PHA. The biological and immunological significance of these results is discussed. PMID- 1612637 TI - Up-regulation of IL-2 induced lymphokine activated killer cell activity by cisplatin and FK-565: involvement of calcium ion. AB - As reported earlier, the IL-2 induced lymphokine activated killer (LAK) activity is significantly up-regulated in the presence of cisplatin/FK-565. Based on these observations, we have investigated whether calcium is involved in the generation of LAK activity by IL-2 alone or along with CP/FK-565. We have shown that treatment of PBMC with IL-2 for four days caused an increase in intracellular free calcium and in ATP levels, which were further significantly enhanced when LAK cells were generated in the presence of CP/FK-565. Depletion of calcium resulted in decreased cytotoxic activity. Addition of tumor cells to LAK cells, generated in the presence of IL-2 alone or along with CP/FK-565 caused an instant rise in intracellular free calcium which was significantly decreased when an increase in intracellular free calcium was observed in calcium-free, EGTA containing buffer. These data suggest that calcium is required for the activation and manifestation of lytic activity by LAK cells. Further, we observed that the increase in intracellular free calcium is not associated with the blastogenic response of peripheral blood mononuclear cells in response to treatment of IL-2 alone or together with CP/FK-565. PMID- 1612638 TI - Bidirectional control by glycyrrhizin of the growth response of lymphocytes stimulated through a receptor-bypassed pathway. AB - This study demonstrates a unique action of glycyrrhizin (GL) in bidirectionally controlling the growth response of lymphocytes stimulated through a receptor bypassed pathway by calcium ionophore A23187 and phorbol 12-myristate 13-acetate (PMA). GL up-regulated the response of lymphocytes in vitro to lower concentrations of A23187 and PMA, and down-regulated the response to higher concentrations. We also provide evidence that GL controls the response of lymphocytes of different cell types or maturation stages in different ways, probably because these lymphocytes require different levels of signals as optimum. Finally, the GL-mediated bidirectional controls of the lymphocyte growth response were shown to be adherent cell-independent. The bidirectional controls demonstrated may be significant in normalizing the lymphocyte responses to very weak or very high stimuli. PMID- 1612639 TI - Binding of perforin to membranes is sensitive to lipid spacing and not headgroup. AB - When triggered, cytolytic effector cells (cytolytic T-lymphocytes (CTL) and large granular lymphocytes (LGL)) release effector molecules from cytoplasmic granules, including the lytic protein perforin. This protein binds and incorporates into the plasma membrane of target cells, where it aggregates to form pores which cause target cell lysis and death. Phosphorylcholine, the headgroup of the ubiquitous phospholipids phosphatidylcholine (PC) and sphingomyelin, has been proposed as the specific receptor for perforin. We report here that any headgroup specificity is outweighed by phospholipid spacing in determining binding of perforin to liposomes. We also find that the spacing of outer leaflet lipids in a natural bilayer, the plasma membrane of the erythrocyte, influences susceptibility of the cell to perforin-mediated lysis. Finally, we demonstrate that the plasma membrane lipids in CTL are more closely spaced than in target cells, suggesting that lipid spacing contributes to the relative resistance of CTL to perforin-mediated lysis. PMID- 1612640 TI - Induction of FMLP-mediated calcium mobilization requires crosslinking of surface immunoglobulin in Daudi cells. AB - We have explored the requirements for the induction of the N-formyl-methionyl leucyl-phenylalanine (FMLP) response in Daudi cells after anti-immunoglobulin treatment. Our results indicate that (a) induction of responsiveness to FMLP was observed in Daudi only after crosslinking of surface immunoglobulin by anti immunoglobulin; (b) this induced responsiveness was not observed in Ramos or Wil 2 cells; (c) the F(ab')2 fragment was sufficient for the induction of the FMLP response, but the Fab fragment and the Fc fragment were ineffective; (d) of the many agents active in B lymphocyte regulation which were tested, none were as effective as anti-immunoglobulin in the induction of the FMLP response; and (e) three inhibitors of calcium mobilization (W-7 (N-(6-aminohexyl)-5-chloro-1 naphthalene sulfonamide), PMA (phorbol 12-myristate 13-acetate), and colchicine), acting on distinct mechanisms, inhibited both the calcium mobilization due to anti-immunoglobulin and the induction of responsiveness to FMLP. Our results suggest important determinants in the induction of a calcium-mobilizing FMLP response in cells of B lymphocyte lineage include (a) the cell type, (b) a selective requirement for activation via surface immunoglobulin, and (c) crosslinking of the surface immunoglobulin. PMID- 1612641 TI - Repeated antigenic challenge induces earthworm coelomocyte proliferation. AB - Annelids are able to protect themselves against foreign materials by natural and acquired cellular immunity. The aim of this study was to characterize the kinetic of antigen induced proliferation of earthworm coelomocytes. The proliferative activity of free coelomocytes of Eisenia foetida decreased after a second contact with the same antigen. Precursor cells in the mesenchymal lining of the coelomic cavity responded to stimulation immediately. These results indicate that for a successful triggering of the proliferative response of the free coelomocytes repeated contact with stimulating agents is needed. PMID- 1612642 TI - Effects of administration of murine recombinant IL-4 on the resistance of mice to Listeria monocytogenes infection. AB - Mice given recombinant murine interleukin-4 as a single i.v. bolus concomitant with a Listeria monocytogenes challenge did not display increased anti-listeria resistance. Under certain conditions, IL-4 administration slightly increased the bacterial burdens in the spleens and livers of infected mice. This finding is consistent with previous reports that endogenous IL-4, or transfer of IL-4 producing TH2 cells, can be detrimental to host defense against microbial infection. PMID- 1612643 TI - Constitutive expression of CD69 in interspecies T-cell hybrids and locus assignment to human chromosome 12. AB - In this study we describe the generation and characterization of interspecies somatic cell hybrids between human activated mature T cells and mouse BW5147 thymoma cells. A preferential segregation of human chromosomes was observed in the hybrids. Phenotypic analysis of two hybrids and their clones demonstrated coexpression of CD4 and CD69 antigens in the same cells. Segregation analysis of an informative family of hybrids followed by molecular and karyotype studies clearly demonstrated that the locus encoding CD69 antigen mapped to human chromosome 12. Although the expression of CD69 antigen is an early event after T lymphocyte activation and rapidly declines in absence of exogenous stimuli, in the hybrids described in this study the expression was constitutive, similarly to what was previously found in early thymocyte precursors and mature thymocytes. In this respect it was important to note that the behavior of the hybrids in culture strongly suggested a dominant influence of the thymus-derived mouse tumor cell genome in controlling the constitutive expression of human CD69. These hybrids may thus provide a system to study the genetic and molecular mechanisms controlling the expression and function of this activation antigen. PMID- 1612644 TI - Structure of CD8 alpha and beta chains of the orangutan: novel patterns of mRNA splicing encoding hingeless polypeptides. PMID- 1612645 TI - Some comments on calibration of molecular evolutionary rates. PMID- 1612646 TI - Sequence analysis of three novel DRw14-DRB1 alleles. PMID- 1612647 TI - Evolutionary relationships among the primate Mhc-DQA1 and DQA2 alleles. AB - The variation of the Mhc-DQA1 and DQA2 loci of ten different primate species (hominoids and Old World monkeys) was studied in order to obtain an insight in the processes that generate polymorphism of major histocompatibility complex (Mhc) class II genes and to establish the evolutionary relationships of their alleles. To that end nucleotide sequences of 36 Mhc class II DQA1 and seven DQA2 second exons were determined and phylogenetic trees that illustrate their evolutionary relationships were constructed. We demonstrate the existence of four primate Mhc-DQA1 allele lineages, two of which probably existed before the separation of the ancestors of the hominoids and Old World monkeys (approximately 22-28 million years ago). Mhc-DQA2 sequences were found only in the hominoid species and showed little diversity. We found no evidence for a major contribution of recombinational events to the generation of allelic diversity of the primate Mhc-DQA1 locus. Instead, our data suggest that the primate Mhc-DQA1 and DQA2 loci are relatively stable entities that mutated primarily as a result of point mutations. PMID- 1612648 TI - Nomenclature for factors of the HLA system, 1991. The WHO Nomenclature Committee for factors of the HLA system. PMID- 1612649 TI - Comparative mapping of IGHG1, IGHM, FES, and FOS in domestic cattle. AB - The immunoglobulin genes have not been genetically characterized as thoroughly in cattle as in other mammals, particularly humans and mice. Comparative gene mapping in mammals suggests that the bovine immunoglobulin heavy chain genes, IGHG4 and IGHM might be syntenic with the FOS oncogene. Interestingly, however, when these genes were assigned to bovine syntenic groups utilizing a panel of bovine: hamster hybrid somatic cells, IGH genes were shown to be syntenic with the FES oncogene rather than FOS. In this study IGH and FES were assigned to Bos taurus chromosome 21 while FOS was assigned to chromosome 10. In addition, bovine specific immunoglobulin-like sequences were observed in the hybrid somatic cells, and one, IGHML1, was mapped to bovine syntenic group U16. The probes used for somatic-cell mapping were also used to screen a small number of cattle of several different breeds for restriction fragment length polymorphisms. IGHG4 and IGHM were shown to be highly polymorphic, while FOS and FES were not. PMID- 1612650 TI - Reptilian class I major histocompatibility complex genes reveal conserved elements in class I structure. AB - The polymerase chain reaction was used to isolate clones with class I major histocompatibility complex sequences from fish (carp), amphibian (axolotl), and two species of reptile (lizard and snake). The lizard and snake clones were used to isolate class I cDNA clones. All the sequences showed the expected evolutionary relatedness. The carp and axolotl clones and one lizard cDNA clone lacked the first cysteine in the alpha 3 domain which in other class I heavy chains forms an intradomain disulfide bond. A small number of amino acid residues are conserved in the class I heavy chain sequences from all five classes of vertebrates. In the first two domains they are symmetrically clustered and contribute to intra- and interdomain contacts. None of these invariant residues are at peptide-binding, T-cell receptor-interacting, or CD8-binding positions. PMID- 1612652 TI - Important laboratory animal resources: selection criteria and funding mechanisms for their preservation. Committee on Preservation of Laboratory Animal Resources. PMID- 1612651 TI - Definition of microsatellite size variants for Tnfa and Hsp70 in autoimmune and nonautoimmune mouse strains. AB - We have cloned and sequenced the upstream regulatory region of tumor necrosis factor alpha (Tnfa) gene in 12 different mouse strains and identified an allelic polymorphism in the upstream regulatory region of the mouse Tnfa gene. The TNF allele found in the NZW strain is distinct from those of all other H-2 haplotypes, supporting our previous suggestion that this allele may be associated with a regulatory or structural defect. In addition, simple tandem repeat sequences (microsatellites) within the promoter region of the Tnfa gene and the 3' untranslated region of one of the members of the HSP70 family (Hsp68c clone) were utilized as genetic markers. Ten TNF size variants and twelve HSP70 variants were identified in over forty mouse strains. Using these markers in a set of congenic mice, we mapped this member of the HSP70 family to the central portion of the H-2 complex, centromeric to the Tnfa gene. The NOD and NZW strains carry unique HSP70 alleles based on the variability in the length of this marker. These findings raise the possibility that this protein may play a role in the association of the major histocompatibility complex with these autoimmune diseases. PMID- 1612653 TI - EEG recognition of holoprosencephaly and Aicardi syndrome. AB - Two cases of alobar holoprosencephaly and two of Aicardi syndrome are reported for their highly specific electroencephalographic (EEG) changes. The asynchronous sharp waves and spikes over the frontal regions with decreasing gradient of potential to the occipital leads were seen in alobar holoprosencephaly while burst suppression pattern with total asynchrony between the two hemispheres was seen in Aicardi syndrome. Even though EEG changes cannot be pathognomic of any abnormality, it is suggested that as in conditions like subacute sclerosing panencephalitis and petitmal epilepsy, so also in alobar holoprosencephaly and Aicardi syndrome, the characteristic features seen on EEG may provide the initial clue to the correct diagnosis. PMID- 1612654 TI - Evaluation of clinico-immunological parameters in pediatric ABPA patients. AB - Allergic bronchopulmonary aspergillosis patients (ten in the age group 5-13) were studied with respect to clinical and immunodiagnostic tests. All the patients showed wheal and flare reaction with A. fumigatus antigens. Clinical features included bilateral infiltration and hilar lymphadenopathy. Eosinophilic count in these patients was observed to be in the range of 300-2500/mm3. Sera of six patients indicated precipitin reaction with A. fumigatus antigens. An elevated total serum IgE was noticed in all the patients. A. fumigatus specific IgG and IgE antibodies were increased in these patients. Optical density of the sera of all the patients against controls were observed to be in the range of (0.426 to 1.8 for IgG and 0.147 to 0.562 for IgE) by ELISA. Western blot analysis indicated that there may be correlation between the clinical stages of the disease and immunological reactivity of the sera with various antigenic components. PMID- 1612655 TI - Intracranial metastasis in Ewing's sarcoma. PMID- 1612656 TI - Acute suppurative thyroiditis in children. PMID- 1612658 TI - Current status of management of neonatal chylothorax. PMID- 1612657 TI - Priapism in chronic myelogenous leukemia. PMID- 1612659 TI - Single umbilical artery: prenatal diagnosis. PMID- 1612660 TI - Physiological principles of mechanical ventilation of the newborn. PMID- 1612661 TI - Visual impairment: its peripheral and central components. PMID- 1612662 TI - Growth monitoring can and does work! An example from the Tamil Nadu Integrated Nutrition Project in rural south India. PMID- 1612663 TI - Breath Counter: a new device for household diagnosis of childhood pneumonia. AB - Illiterate Traditional Birth Attendants (TBAs) were trained to diagnose pneumonia in children using their visual judgement of tachypnoea. This method resulted in 41% wrong diagnosis in the cases with borderline respiratory rate. A simple device, named 'Breath Counter' was designed and TBAs were trained to diagnose pneumonia in children using this instrument. The agreement of TBAs' diagnosis, with diagnosis using WHO criteria of respiratory rate improved from unaided 60% (30/50) to 82% (41/50) by the use of Breath Counter (p less than 0.05). Breath Counter is simple, cheap, effective and can be used even by illiterate persons to diagnose pneumonia in children. It has the potential of becoming a household diagnostic aid. PMID- 1612664 TI - Foetal growth parameters--clinical versus ultrasonographic. AB - The study was conducted in 2831 pregnant women with no diagnosed complication at the time of registration to obtain normal foetal growth pattern for clinical and ultrasonographic parameters. Normal values for maternal weight, fundal height and abdominal girth for clinical and biparietal diameter, abdominal circumferences and femoral length for ultrasonographic parameters are presented. Clinical and ultrasonographic parameters were compared for their efficacy in prediction of low birth weight. Neither clinical nor ultrasonographic parameters were found to be satisfactory in identifying the foetus at risk of low birth weight. It has been found that clinical parameters for routine monitoring are as effective as ultrasonographic parameters and have the added advantage of being easily replicable at the peripheral level of health care. PMID- 1612665 TI - XXIX National Conference of Indian Academy of Pediatrics, Nagpur. January 9th to 12th, 1992. PMID- 1612666 TI - Pediatric pulmonary function testing. PMID- 1612667 TI - Peak expiratory flow rates of healthy tribal children living at high altitudes in the Himalayas. AB - Peak expiratory flow rates (PEFR) of 237 healthy tribal children living at or above 3000 metres from sea level were measured. The mean age, height and PEFR for boys were 10.7 years, 130.7 cm, 245.5 +/- 74.0 l/min, respectively. The values of these parameters in girls were 10.5 years, 128.2 cm and 222.3 +/- 78.6 l/min. The PEFR of these children, especially for boys, were comparable with North Indian urban children or children of the West. PMID- 1612668 TI - Therapeutic and diagnostic role of bronchoscopy in pediatric age group. AB - Two hundred and seventy five cases were evaluated bronchoscopically for various respiratory conditions. In 140 cases, a foreign body and in 30 cases mucus plug was removed. In 47 cases there was inflammation of the tracheobronchial tree. Forty patients with empyema thoracis were evaluated bronchoscopically because of persistence of bronchopleural fistula or continued pus discharge from intercostal tubes not responding to the routine treatment. The purpose of the article is to stress the therapeutic as well as diagnostic aspect of bronchoscopy for various respiratory conditions in pediatric age group. PMID- 1612669 TI - Culture appropriate indicators for monitoring growth and development of urban and rural children below 6 years. AB - In this cross sectional study, 2000 apparently normal children aged 0-6 years (1200 urban and 800 rural), were nutritionally and developmentally assessed and their environment scrutinized for possible risk factors. Measurement of mid upper arm circumference (MUAC) using standard techniques revealed malnutrition in 44% of the rural and 24% of the urban children especially in the 2-6 years of age group. Culture appropriate indicators of psycho-social development picked up gross delays in gross motor (GM), vision and fine motor (V&FM) and language skills. Self help, concept hearing (SHCH) skills were recorded as normal while social skills were advanced particularly in the 0-2 years old urban group. By the use of the family protocols, low socio-economic status, malnutrition and 9 other risks factors have been generated for the urban group. No risk factor could be identified for the rural group. Better income emerged as the only real protective factor for the sample showing a direct positive relationship with the 45 skills tested, especially in the 2-6 years age group. Nineteen developmental skills were identified as powerful predictors of development. A prototype home based screening record was constructed for monitoring of growth and development which can be even used by minimally trained primary care worker. PMID- 1612670 TI - Significance of cord problems at birth. AB - Cord problems at birth were prospectively studied in 12,000 singleton deliveries, of which 258 (2.15%) babies had cord abnormalities. Nearly 32% of these cases had fetal distress and 20.5% had 1 minute Apgar score less than 6. Of the various cord problems nuchal cord was noted in 79.1%, cord prolapse in 12.4% and true knots in 3.9% cases. Perinatal mortality rate with cord problems was 85.27/1000 births. Neonatal problems noted were septicemia (4.56%), aspiration syndromes (13.48%), hypoxic ischemic encephalopathy (7.30%), neonatal convulsions (2.14%) and hyperbilirubinemia (2.14%). Although mean Hb and PCV were lower in those with cord round the neck as compared to normal controls, this difference was not significant. Seven babies had Hb less than 13 g/dl with nuchal cords. Neonates born with cord around the neck or with other cord abnormalities should be carefully followed up for morbidity. PMID- 1612671 TI - Occurrence of multi-resistant Salmonella typhimurium infection in a pediatric hospital at Calcutta. AB - Salmonella typhimurium was isolated from 55 (15.9%) of the 347 hospitalized diarrheal children and 14 (11.1%) of the 126 non-diarrheal controls. All the 98 asymptomatic children attending hospital outpatients were negative. Six (3.7%) of the 162 samples of different categories examined from the hospital were positive for S. typhimurium. Finger washing of one female food handler, feces of two cats of the wards, surface of wash basin, lavatory seat and shelf yielded positive isolations. In vitro antibiotic sensitivity testing showed majority of the strains were resistant against commonly used antimicrobial agents while they were uniformly sensitive to norfloxacin and ciprofloxacin. The present study points to cross-infection by multi-resistant S. typhimurium strains in the hospital wards. PMID- 1612672 TI - Therapy of symptomatic patent ductus arteriosus in preterms using mefenemic acid and indomethacin. AB - Mefenemic acid (MA) was given in three doses of 2 mg/kg/dose at 12 hourly intervals in 16 cases clinically suspected of having symptomatic patent ductus arteriosus (PDA). All babies were 35 weeks gestation (mean 30.1 weeks) and weighed less than or equal to 1700 g at birth (mean 1320 g), the mean age of administration of MA being 16 days. Of the 16 cases, two did not respond to therapy. One non-responder was subsequently shown to have an endocardial cushion defect without PDA on 2-D Echo and Doppler study. The other was 29 days old at the initiation of therapy. In once case, the ductus reopened after an initial closure, however, it closed on repeating a second course of the drug. Thirty preterms (less than or equal to 34 weeks) who were earlier treated with three doses of indomethacin (0.25 mg/kg/dose) formed the comparative study group. The closure rate of PDA on treatment with indomethacin was 70% and that with MA was 93.3% (p greater than 0.05). Two neonates treated with MA and two treated with indomethacin had feeding intolerance and vomiting, perhaps attributable to the drug therapy. We recommend the use of MA for closure of symptomatic PDA in preterms, especially in those cases where indomethacin is not tolerated or when minute titration of its dosage is impracticable. PMID- 1612673 TI - Spectrum of neonatal hyperbilirubinemia: an analysis of 454 cases. AB - A prospective study of 454 newborn babies with pathological hyperbilirubinemia revealed that in about one-third of cases (34.6%), no cause could be identified despite detailed investigations. Nearly three-fifth of infants (62.5%) had hyperbilirubinemia due to hemolytic causes. On the basis of four variables, i.e., peak serum bilirubin level, age of attaining the peak level, age of starting phototherapy and total duration of phototherapy, the cases of hyperbilirubinemia can be categorized into three groups: (a) Group I (mild) included non-hemolytic hyperbilirubinemia, i.e., idiopathic, bacterial infections, intrauterine infections and others, (b) Group II (moderate) comprised of hemolytic as well as non-hemolytic hyperbilirubinemia due to prematurity, administration of oxytocin, bruising/cephalhematoma, and (c) Group III (severe) comprised of hyperbilirubinemia due to hemolysis as a result of blood group incompatibility between the mother and the neonate and G-6-PD deficiency. Sixty six babies required exchange blood transfusion (EBT) and a total of 100 EBTs were performed. Most of the babies (80.3%) requiring exchange blood transfusion belonged to Group III. The most common cause of hemolytic hyperbilirubinemia needing exchange blood transfusion was Rh isoimmunization followed by G-6-PD deficiency and ABO isoimmunization. There was no death attributable to the procedure of exchange blood transfusion. PMID- 1612674 TI - A bacteriological study of the environment of pediatric ward and neonatal nursery. AB - The hospital environment is full of pathogens which may cause nosocomial infections. A bacteriological survey of hospital air, floor, water, milk and fomites was done. The air survey showed large number of bacteria carrying particles in air. A direct relation between floor area per person and bacterial contamination of air was established. The floor survey showed that there is abundance of bacteria on the hospital floors, much more than the accepted fair standards of house keeping. The hospital water had a high coliform and total bacterial count and stored tank water was more dirty. Neonatal nursery milk also had high total bacterial and coliform counts. Regular surveillance of hospital environment may help to reduce the incidence of cross infection. PMID- 1612675 TI - Obstetric and infant feeding practices in Punjab: effect of educational intervention. AB - A survey of obstetric and infant feeding practices in 100 mothers showed that only 17% infants were exclusively breast fed. Antenatal advice regarding breast feeding was given to only 13%. Sixty eight per cent infants were put to breast 24 hours after delivery. Campaign against bottle feeding was then launched. Fifteen months later, a survey on another 100 mothers showed that 44% infants were exclusively breast-fed, antenatal advice was given to 11% mothers and 60% mothers got active postnatal advice regarding disadvantages of bottle feeds. Incidence of exclusive breast feeding was more in infants who were roomed-in with the mother early, started on breast feeding earlier and whose mothers received antenatal advice. It was concluded that even if the percentage of antenatal advice did not improve, active postnatal campaign directed towards dangers of bottle feeding could increase the prevalence of exclusive breast feeding. PMID- 1612676 TI - Anesthetic management of cleft lip and cleft palate. PMID- 1612677 TI - Aminoglycosides. PMID- 1612678 TI - Hemoglobinopathies during infancy in western Orissa. PMID- 1612679 TI - Lymphangioma of tongue. PMID- 1612680 TI - Nitroblue tetrazolium test in protein energy malnutrition. PMID- 1612681 TI - Values for mouth and ear measurements in newborns. PMID- 1612682 TI - Pyocolpos. PMID- 1612683 TI - Serum iron and total iron binding capacity in anemias in children. PMID- 1612684 TI - Dermal organophosphorus poisoning in a girl with a hip spica. PMID- 1612686 TI - Acute carbamazepine poisoning. PMID- 1612685 TI - Acute mercury vapor poisoning. PMID- 1612688 TI - Follow-up of children surgically treated for nodular goitre. PMID- 1612687 TI - Gingival fibroma: an unusual presentation. PMID- 1612689 TI - Lead poisoning due to environmental pollution. PMID- 1612690 TI - Ciprofloxacin current status in pediatric practice. PMID- 1612691 TI - Congenital pulmonary cyst. PMID- 1612692 TI - Nosocomial infections in pediatric and neonatal ward of Umaid Hospital, Jodhpur: a cross-sectional study. PMID- 1612693 TI - Sodium valproate in Sydenham's chorea. PMID- 1612694 TI - Pulmonary function testing in office practice. PMID- 1612695 TI - Apnea, bradycardia and periodic breathing: are they always pathological? PMID- 1612696 TI - [Cast posts and cores]. PMID- 1612698 TI - [Dentures on osseointegrated implants after periodontitis treatment]. PMID- 1612697 TI - [Choice of abutment type in the Branemark system]. PMID- 1612699 TI - [Root caries. An important problem in the elderly]. PMID- 1612700 TI - [Electronic probes]. PMID- 1612701 TI - [The assistant and risk of infection in the dental office]. PMID- 1612702 TI - [Indications and limits of photopolymerizing adhesives for cast ceramic]. PMID- 1612703 TI - [Alginates in fixed prosthodontics]. PMID- 1612704 TI - [Lingual orthodontics: for or against?]. PMID- 1612705 TI - [Oral Burkitt's lymphoma and ORL in a child]. PMID- 1612707 TI - [Informed consent]. PMID- 1612706 TI - [Treatment in general practice of a complex periodontitis case]. PMID- 1612708 TI - [The occlusal reference plane in removable partial dentures]. PMID- 1612709 TI - [Extractions and implants]. PMID- 1612710 TI - [The role of the assistant in treatment of complete edentulism with removable dentures]. PMID- 1612711 TI - Universal access to affordable health care. PMID- 1612712 TI - Building a private-public partnership that works. PMID- 1612713 TI - Employer-based private health insurance needs structural reform. AB - This paper argues that certain structural barriers in our employer-based health insurance system inevitably mean failure by employers, private insurers, and physicians to produce a system that provides affordable health care and insurance to the entire population with a minimum of government regulation and intervention. Key barriers that lead to failure in managing the physician-patient transaction and the competition among health care/health insuring plans are described. Finally, the minimal scale of needed reform is discussed. PMID- 1612714 TI - Expanding employment-based health insurance: is small group reform the answer? AB - Nearly two-thirds of all uninsured workers are employed in firms with 100 or fewer employees. Making insurance more affordable and available to small groups is high on the political agenda. Efforts to reform the small group market include making insurance more available by restricting the use of medical underwriting to deny access, and compressing rates to make it more affordable for high-risk groups. Other reforms pursued at the state level have focused on reducing the price of insurance facing all small employers. My analysis suggests that these proposals will have limited success in reducing the number of uninsured. Short of compulsory insurance, significant changes will occur only when insurance is organized around larger purchasing groups and not small employers. PMID- 1612715 TI - Risk variation and fallback insurers in universal coverage insurance plans. AB - This paper argues that optimal treatment of health expenditure risk variation over one's lifetime requires partial offsetting of experience-related premium fluctuations. It argues that government should provide protection against the risk of serious chronic illness by offering risk-related tax credits that offset some (though not all) of the changes in premiums due to such illnesses. The performance of a fallback insurer, present in most market-based health reform proposals, is shown to depend on whether or not it is permitted to risk rate. Forbidding any risk rating is likely to cause adverse selection problems, whereas permitting the fallback insurer to risk rate should help it to perform its proper role and avoid being subject to dumping of high risks. PMID- 1612716 TI - Insurer competition and protection from risk redefinition in the individual and small group health insurance market. AB - Analyses of problems in the health insurance market usually focus on the individual and small group market. Consumers in this market who experience an illness or diagnosis of illness in one time period are likely to have their future risk redefined by insurers. Despite the fact that risk-averse consumers should desire protection against redefinition of risk, policies featuring that protection currently are not common in the individual and small group market. Contracts offering that protection must either be offered by pools that can guarantee replenishment of good risks over time, or be multiperiod contracts. Risk replenishment is impossible for individuals and may be technically difficult for many small groups. Also, the terms of multiperiod contracts with a single insurer may be unattractive to individuals and small groups, given the current structure of the market. Multiperiod contracts with a pool, rather than an individual insurer, may make it possible for individuals and small groups to enjoy the same advantages as consumers who obtain employment-based health insurance through large firms. PMID- 1612717 TI - Reform of financing for health coverage: what can reinsurance accomplish? AB - Reinsurance is one way that insurance companies pool risk, in this case, across insurance companies. Under conventional private practice, primary health insurers, including self-insured groups and HMOs, voluntarily contract with reinsurers to share some risk and some premiums. Because the primary carrier mainly wants to protect its solvency against unpredictable variation in claims experience, it normally reinsures only the "high end" of claims risk. This retrospective coverage of unusually high losses helps primary insurers take on more risk than they otherwise could. But it does not help secure affordable coverage for people with prospectively known high risks. Some plans for reforming private health insurance also invoke reinsurance-like mechanisms, especially in the markets for individual and small group coverage. There, reinsurance serves as part of a strategy for requiring that primary insurance be made available to all applicants, regardless of risk. Reinsurance or similar rules for allocating the burden of unusually high risks can help keep any one private insurer from having to bear a disproportionate share of high risks, and thus extend the reach of private insurance markets through regulation. But reinsurance alone does not reduce the underlying high cost of providing such primary coverage. Nor can reinsurance alone provide the resources to cover the uninsured, ensure that insurers will want to cover them, or make them voluntarily buy private coverage. Only some combination of new subsidies and mandates can do that. PMID- 1612718 TI - A test of our society: how and for whom we finance long-term care. AB - Financing long-term care remains an issue of great national interest, but little action. This lack of action is due to a lack of consensus regarding both what we mean by long-term care and what roles the private and public sectors should play. Different solutions have been offered, some focusing on the public sector and others on the private. The reality is that financing the needed care will require participation of both sectors, as well as a redefinition of their roles that makes them complementary rather than competitive, as is now the case. This partnership can take many forms, but must, at a minimum, reflect an explicit societal commitment to what our population is entitled to with respect to long term care; develop the infrastructure that meets the total--as opposed to only the medical--needs of the population; and make more efficient use of the resources that can be brought to bear on the problem. PMID- 1612719 TI - Policy reform as creative destruction: political and administrative challenges in preserving the public-private mix. AB - As political pressure for affordable universal coverage intensifies, various proposals have been crafted to improve the system without sacrificing the role of the private sector. Some analysts view the preservation of a mixed public-private system as an exercise in incrementalism, avoiding disquieting departures from familiar arrangements. A review of the political and administrative challenges of several main options--market innovation, tax credits, play or pay, and Medicaid expansion--suggests that the path to true reform is a slippery slope. Over time, changes in particular sectors, such as insurance, employers, government, and providers, will very likely implicate the others too. Although redefining the public-private mix may be more incremental than (say) adoption of a Canadian model, it will also entail considerable "creative destruction" of existing patterns and cannot fail to disturb the institutional status quo substantially. PMID- 1612720 TI - Including an all-payer reimbursement system in a universal health insurance program. AB - This article examines the feasibility of including an all-payer reimbursement system in a universal health care program in the United States. An all-payer system would keep intact the current array of private and public insurers, but would require that they each pay the same price for hospital and physician services. The article concludes that an all-payer system would face far fewer political barriers than a purely government-financed system. Furthermore, it has a number of advantages over the financing schemes currently used, particularly with respect to enhancing access to care and controlling costs. But there are several potential problems: agreeing on a common payment rate; controlling the volume of services provided; devising a way of incorporating alternative delivery systems; and dealing with the issue of whether providers will be able to "balance bill". The extent to which these problems can be solved will, to a large degree, determine whether an all-payer system can live up to its promise. PMID- 1612721 TI - Empowering the demand side: from regulation to purchasing. AB - The primary justification for private insurance is the hypothesis that competition among private insurers will lead to an environment in which physicians and hospitals will continually strive to improve the quality and economy of the care they provide, and to be responsive to the preferences of the consumers they serve. However, to date, competition among private insurers has failed miserably in achieving this goal. In order to achieve this goal, competition among insurers must be regulated in an entirely different manner than it is currently. This article describes the ways in which health insurance is currently regulated, and argues that passive regulation directed at assuring financial solvency of insurers should be transformed into an active purchasing authority. This purchasing authority would empower the demand side, creating an environment of managed competition that rewarded those provider groups able to offer high quality, economical care. PMID- 1612722 TI - Who pays for health care in the United States? Implications for health system reform. AB - This paper examines the distribution of health care spending and financing in the United States. We analyze the distribution of employer and employee contributions to health insurance, private nongroup health insurance purchases, out-of-pocket expenses, Medicaid benefits, uncompensated care, tax benefits due to the exemption of employer-paid health benefits, and taxes paid to finance Medicare, Medicaid, and the health benefit tax exclusion. All spending and financing burdens are distributed across the U.S. population using the Urban Institute's TRIM2 microsimulation model. We then examine the distributional effects of the U.S. health care system across income levels, family types, and regions of the country. The results show that health care spending increases with income. Spending for persons in the highest income deciles is about 60% above that of persons in the lowest decile. Nonetheless, the distribution of health care financing is regressive. When direct spending, employer contributions, tax benefits, and tax spending are all considered, the persons in the lowest income deciles devote nearly 20% of cash income to finance health care, compared with about 8% for persons in the highest income decile. We discuss how alternative health system reform approaches are likely to change the distribution of health spending and financing burdens. PMID- 1612723 TI - Can a universal coverage system temper the underwriting cycle? AB - The health insurance industry has experienced a pronounced six-year cycle of earnings for nearly three decades--three years of profits followed by three years of losses. This profitability cycle triggers a turbulent pricing cycle. After reviewing three schools of thought about the causes of the cycle, in this article we examine new evidence to determine the probable impact on the cycle of a private-public, universal coverage, national health plan. We find no evidence of a cycle in the pricing and use of health care services. Since 1985, the relationship between the overall economy and health insurance trends has weakened. We conclude that the root causes of the cycle are essentially internal to the insurance industry, and, therefore, national health care reform will have little impact on the underwriting cycle. PMID- 1612724 TI - Government, private health insurance, and the goal of universal health care coverage. AB - The Health Insurance Association of America advocates joint efforts by federal and state governments and the private sector to achieve the goal of universal access to health care. It recommends several changes in the small employer market to provide greater predictability and protection to those insured, including establishment of private, not-for-profit reinsurance organizations authorized by the states. State risk pools for uninsurable individuals who are not part of an employer group are also proposed. The federal government role would include expanding Medicaid eligibility and exempting all insured plans from state mandated benefits. HIAA's proposal also stresses the continued growth and use of managed care programs. PMID- 1612725 TI - Building a foundation for universal access. AB - Specific strategies outlined by the Blue Cross and Blue Shield Association call for a restructuring of health care financing that builds on a competitive, employer-based health insurance system. Universal access can be achieved through better management of the cost of care and more affordable health care premiums. Restructuring of the financing system must restore its capacity to manage risk and establish accountability for managing cost. Business practices and public policies that have encouraged market fragmentation should be reformed and incentives to create affordable insurance options for all buyers be established. PMID- 1612726 TI - An 80-kilodalton antigen from Histoplasma capsulatum that has homology to heat shock protein 70 induces cell-mediated immune responses and protection in mice. AB - An extract of the cell wall and cell membrane from Histoplasma capsulatum yeast cells was assayed by Western blot (immunoblot) for reactivity with two monoclonal antibodies to heat shock protein 70. Four bands with molecular masses of 80, 66, 54, and 32 kDa bound both antibodies. The 80-kDa protein was isolated, analyzed for homology to heat shock protein 70, and tested for antigenicity and immunogenicity in C57BL/6 mice. The 80-kDa protein reacted with monoclonal antibody to heat shock protein 70. Sera from mice immunized with the antigen recognized H. capsulatum heat shock protein 70. Moreover, the amino-terminal sequence of the 80-kDa protein revealed substantial homology with heat shock protein 70 from several species. The 80-kDa protein induced delayed-type hypersensitivity responses in mice immunized with either viable yeast cells or antigen. Splenocytes from mice immunized with yeast cells or with antigen responded in vitro to the 80-kDa antigen. Immunization of mice with the antigen enhanced host resistance against a sublethal inoculum of H. capsulatum yeast cells, but it did not reduce the mortality of mice given a lethal challenge of yeast cells. Thus, this antigen manifests homology with members of the heat shock protein 70 family. Furthermore, the 80-kDa protein elicits cellular immune responses to H. capsulatum, and it mediates protective immunity. PMID- 1612728 TI - The coccidioidal complement fixation and immunodiffusion-complement fixation antigen is a chitinase. AB - Culture filtrates and autolysates of Coccidioides immitis have provided suitable crude antigens for the serodiagnosis and prognosis of coccidioidomycosis. One of these, a heat-labile antigen which participates in the immunodiffusion reaction corresponding to the complement fixation reaction (IDCF), has been characterized as a 110-kDa native protein that, when subjected to reducing conditions and heat, yields a 48-kDa component. The present report provides serologic and biochemical evidence that this antigen is a chitinase. This chitinase, isolated from 48-h culture filtrate of the spherule-endospore-phase C. immitis by affinity adsorption to chitin, formed a line of identity with the IDCF reference antigen and participated in the complement fixation reaction with human serum. It lost its enzymatic as well as antigenic activity when heated, but when not heated it retained its enzymatic activity even when precipitated with coccidiodal antibody present in human serum. This chitinase represents a significant serodiagnostic substance and may be important in the morphogenesis of C. immitis. PMID- 1612727 TI - In vivo inhibition of lipopolysaccharide-induced lethality and tumor necrosis factor synthesis by Rhodobacter sphaeroides diphosphoryl lipid A is dependent on corticosterone induction. AB - Diphosphoryl lipid A from the lipopolysaccharide (LPS) of Rhodobacter sphaeroides (Rs-DPLA) has been demonstrated to block in mice and guinea pigs the increase in the serum tumor necrosis factor (TNF) response induced by highly purified deep rough chemotype LPS from Escherichia coli D31m4 (ReLPS). The present study was designed to determine the role of corticosterone induction by Rs-DPLA and its effect on TNF regulation and survival in lethal endotoxin shock models and to evaluate the ability of Rs-DPLA to induce endotoxin tolerance. Administration of a 100-fold excess of Rs-DPLA 1 h prior to ReLPS administration inhibited the characteristic peak in serum TNF levels induced by LPS. Inhibition was apparent in normal and D-galactosamine (GalN)-sensitized mice and occurred at the pretranslational level, as splenic TNF and interleukin-1 beta mRNAs were present in lower amounts in LPS-stimulated mice pretreated with Rs-DPLA. Consistent with its effects in reducing serum TNF levels, Rs-DPLA pretreatment protected GalN sensitized mice from a lethal ReLPS challenge. In contrast, Rs-DPLA did not inhibit the increase in the serum TNF response or protect against a lethal ReLPS challenge in parallel experiments with adrenalectomized (Adrex) mice, for which the 50% lethal dose of ReLPS was comparable to that for GalN-sensitized mice. Furthermore, Rs-DPLA appeared to prime Adrex animals and increase the magnitude of the serum TNF response to a suboptimal LPS stimulus. Priming by Rs-DPLA, however, was not observed in normal or GalN-sensitized mice. Although Rs-DPLA by itself was nontoxic and unable to elevate serum TNF levels in any of the models investigated, it did induce a significant increase in the serum corticosterone response and was capable of inducing endotoxin tolerance in normal mice. The inability of Rs-DPLA to protect Adrex mice from a lethal ReLPS stimulus or to inhibit the increase in the serum TNF response suggests that the protective effect of Rs-DPLA in normal or GalN-sensitized animals occurs through corticosterone induction. These results support the concept that endogenous glucocorticoids can modulate the endotoxic effects of LPS by inhibiting the synthesis of inflammatory cytokines. PMID- 1612729 TI - Oral ingestion of egg yolk immunoglobulin from hens immunized with an enterotoxigenic Escherichia coli strain prevents diarrhea in rabbits challenged with the same strain. AB - White Leghorn hens were immunized with enterotoxigenic Escherichia coli B16-4 with heat-labile enterotoxin and colonization factor antigen I in Freund's adjuvant. Specific antibodies were detected by an enzyme-linked immunosorbent assay in the serum after 8 days and in eggs after 10 days, with levels reaching peaks at 15 and 20 days after the first immunization, respectively. The protective effects of the egg yolk antibodies were tested in the rabbit reversible ileal tie model of diarrhea. Five control rabbits developed severe diarrhea within 72 h after inoculation with enterotoxigenic E. coli B16-4. Oral ingestion of egg yolks from immunized hens for 4 days prior to inoculation protected five rabbits from diarrhea after challenge with the same strain of E. coli. The rabbits showed no adverse effects from the ingestion of the egg yolks. Four rabbits fed control eggs were also afforded some protection in that three rabbits developed mild diarrhea and one rabbit remained entirely well. In vitro experiments showed that immunoglobulin from egg yolks interfered with the binding of E. coli to purified small bowel mucins; immunoglobulin from immunized hens reduced binding more than immunoglobulin from nonimmunized hens. These findings indicate that eggs from hens immunized with appropriate antigens have potential as a useful source of passive immunity. PMID- 1612730 TI - Antibody-secreting cells in human peripheral blood after oral immunization with an inactivated enterotoxigenic Escherichia coli vaccine. AB - Vaccine antigen-specific antibody-secreting cell (ASC) responses in peripheral blood of healthy adult volunteers were studied after oral immunization with a prototype enterotoxigenic Escherichia coli (ETEC) vaccine by means of the enzyme linked immunospot technique. Three doses of vaccine consisting of formalin-killed ETEC bacteria expressing fimbrial colonization factor antigens I and II (CFA/I and CFA/II) in combination with purified cholera toxin B subunit (CTB) were given 2 weeks apart. The ASC responses were detected 7 days after each immunization. Immunoglobulin A (IgA) was the predominant isotype produced by CFA/I- as well as CFA/II-specific ASCs. Moderate CFA/I- and CFA/II-specific IgM-secreting ASC (IgM ASC) responses were also seen, whereas IgG-ASC responses to either of the CFAs were negligible. The ASC responses to CTB, on the other hand, comprised both IgA- and IgG-ASCs, with few if any specific IgM-ASCs. Almost 90% of the volunteers developed CFA-specific ASC responses after vaccination. Maximal CFA-specific ASC responses were usually observed after a single dose or two doses of vaccine. A third dose of vaccine did not result in increased but rather resulted in decreased magnitudes of CFA-specific ASC responses. Furthermore, it was found that CTB did not function as a mucosal adjuvant, since CFA-specific ASC responses were not enhanced by the simultaneous administration of CTB. These results suggest that two oral doses of ETEC vaccine induce a strong mucosal immune response, as reflected by the presence of large numbers of antigen-specific mucosal B cell immunoblasts in the blood. PMID- 1612731 TI - Induction of tumor necrosis factor and interleukin-1 by purified staphylococcal toxic shock syndrome toxin 1 requires the presence of both monocytes and T lymphocytes. AB - Highly purified staphylococcal toxic shock syndrome toxin 1 (TSST-1) was tested for its ability to induce the cytokines tumor necrosis factor (TNF) and interleukin-1 (IL-1) from fractionated human peripheral blood mononuclear cells prepared from seven healthy donors. Highly purified monocytes alone or T lymphocytes alone did not produce TNF or IL-1 when incubated with TSST-1 at 37 degrees C for up to 72 h. However, the addition of 10 micrograms of TSST-1 per ml to a 1:1 mixture of monocytes and T cells resulted in significant TNF (predominantly TNF-alpha) and IL-1 beta production after 24 h at 37 degrees C. The nature of the monocyte/T-cell interaction did not appear to involve gamma interferon (IFN-gamma), since 10 micrograms of rabbit anti-IFN-gamma per ml did not neutralize TNF-alpha production after TSST-1 induction. Similarly, L243, a monoclonal antibody to HLA-DR which blocks TSST-1 binding to monocytes, did not inhibit TNF-alpha production following TSST-1 induction. However, direct contact between monocytes and T cells was required, since physical separation of cells in double-chamber culture wells abolished TNF-alpha secretion after TSST-1 stimulation. Furthermore, paraformaldehyde fixation of either monocytes or T cells prior to addition to viable T cells or monocytes, respectively, also abolished TNF-alpha secretion, suggesting that aside from cell contact, soluble factors were also involved. Our results suggest that cytokine production involves more than binding of TSST-1 to its receptor on monocytes alone and that cell contact with T cells and the release of a soluble factor(s) other than IFN-gamma may be essential for the induction of cytokines by this toxin. PMID- 1612732 TI - An arthroconidial-spherule antigen of Coccidioides immitis: differential expression during in vitro fungal development and evidence for humoral response in humans after infection or vaccination. AB - A 33-kDa protein antigen purified from spherules of Coccidioides immitis was analyzed for ultrastructural localization and for binding to serum antibodies from infected or immunized humans. By using colloidal gold detection of affinity purified anti-33-kDa protein antibodies, electron photomicrographs showed binding to the inner cell wall of arthroconidia and spherules and to the septa and glycocalyx surrounding endospores. Enzyme immunoassay measurements also demonstrated that the antigen was most abundant in mature spherules. Of 37 patients with coccidioidomycosis but without concurrent human immunodeficiency virus infections, all but 2 demonstrated immunoglobulin M (IgM) (usually with early infection) or IgG antibodies for the 33-kDa antigen. In contrast, only one of four HIV-infected patients with active coccidioidal infections demonstrated antibody. On the other hand, 107 of 108 patients without evident coccidioidomycosis and 15 of 16 patients with histoplasmosis did not have similar antibodies, indicating a high degree of specificity. Immunization of humans with a spherule vaccine produced IgM responses to this antigen that were not evident in placebo recipients. PMID- 1612733 TI - Murine model of cutaneous infection with gram-positive cocci. AB - Staphylococcus aureus has remained an important cause of nosocomial wound infections, but standardized or reproducible systems for analyzing cutaneous infections caused by S. aureus do not exist. A variety of foreign materials, variable inocula, and skin traumas have been used to promote infection. To minimize these variables and ensure reproducibility, we chose a model using subcutaneous injections of a fixed quantity of dextran microbeads (Cytodex) as the foreign material added to standardized broth suspensions of S. aureus. Suspensions (0.2 ml) injected into an outbred strain of immunocompetent hairless mice generated reproducible, measurable lesions. With S. aureus Smith Diffuse, fluctuant, erythematous lesions with a peak diameter of 15 mm were observed; these lesions yielded purulent material containing gram-positive cocci and neutrophils and yielded growth of S. aureus on culture. Lesion size was proportional to the bacterial inoculum size. Histologic examination of excised lesions revealed typical abscesses. A second strain of S. aureus (SLC3) produced dermonecrosis instead of abscesses at an inoculum size of 10(7) CFU. Control injections with a sterile Cytodex suspension regularly produced nondraining, nonerythematous nodules with maximum diameters of less than or equal to 5 mm. Streptococcus pyogenes produced late-onset necrotic lesions and abscesses. Using a foreign substance, this model generates easily observed and reproducible cutaneous infection with S. aureus and streptococci that can potentially discriminate between inter- and intrastrain differences. Such a model could be used to test the pathogenicity of isogeneic strains of these bacterial species and to evaluate the efficacy of antimicrobial agents. PMID- 1612734 TI - In vivo effects of the antiglucocorticoid RU 486 on glucocorticoid and cytokine responses to Escherichia coli endotoxin. AB - The endogenous adrenocortical response to sepsis is critical for host survival. The in vivo interactions among the endogenous glucocorticoid response, the induction of cytokines, and host survival during endotoxemia were explored in this study by use of the glucocorticoid receptor antagonist RU 486. Male Lewis rats underwent sterile insertion of a right jugular venous catheter. After a 72-h recovery period, animals received a 50% lethal dose of Escherichia coli endotoxin (2.5 mg/kg) via the catheter after pretreatment for 30 min prior to lipopolysaccharide (LPS) treatment with (i) vehicle alone intravenously (i.v.) ( corticosterone [-Cort]/-RU 486/+LPS) (n = 10), (ii) the antiglucocorticoid RU 486 (10 mg/kg) i.v. (-Cort/+RU 486/+LPS) (n = 11), or (iii) RU 486 (10 mg/kg) i.v. in animals that had undergone subcutaneous implantation of a corticosterone pellet at the time of catheter insertion (+Cort/+RU 486/+LPS) (n = 10). Except in animals receiving corticosterone pretreatment, baseline plasma corticosterone levels were low in all groups. Plasma corticosterone levels increased significantly (P less than 0.001) above the baseline following LPS administration. Animals in the -Cort/+RU 486/+LPS-treated group exhibited significantly increased mortality (P less than 0.001), with only 9% of the animals surviving at 72 h, as well as significantly increased plasma interleukin 6 levels, compared with animals receiving the vehicle alone (-Cort/-RU 486/+LPS), which showed 50% mortality. Pretreatment with corticosterone and RU 486 (+Cort/+RU 486/+LPS) significantly (P less than 0.001) reversed the mortality observed with RU 486 pretreatment alone (-Cort/+RU 486/+LPS), with 70% of the animals surviving at 72 h, and significantly attenuated the peak plasma tumor necrosis factor and interleukin-6 responses to LPS, compared with those in the animals treated with vehicle alone. These data demonstrate that the blockade of glucocorticoid binding by RU 486 increases LPS-induced mortality. The reversal of this effect by the induction of hypercorticosteronemia prior to RU 486 and LPS exposure (+Cort/+RU 486/+LPS) improves survival and is further associated with significant attenuation of cytokine production. Therefore, these data suggest that the protective effect of the endogenous glucocorticoid response to acute endotoxemia may result from the down-regulation of a potentially lethal cytokine response. PMID- 1612735 TI - Purification of recombinant Helicobacter pylori urease apoenzyme encoded by ureA and ureB. AB - Helicobacter pylori, a gram-negative, microaerophilic, spiral-shaped bacterium, is an etiologic agent of human gastritis and peptic ulceration and is highly restricted to the gastric mucosa of humans. Urease, synthesized at up to 6% of the soluble cell protein, hydrolyzes urea, thereby releasing ammonia, which may neutralize acid, allowing survival of the bacterium and initial colonization of the gastric mucosa. The urease protein is encoded by two subunit genes, ureA and ureB; however, accessory genes are necessary for enzyme activity. H. pylori urease genes were isolated from a cosmid gene bank and subcloned on a 5.8-kb Sau3A partial fragment carrying ureCDAB, corresponding to four open reading frames described by A. Labigne, V. Cussac, and P. Courcoux (J. Bacteriol. 173:1920-1931, 1991). Clones were confirmed as ureas gene sequences by polymerase chain reaction amplification. The recombinant enzyme was purified from the soluble protein of French press lysates of Escherichia coli DH5 alpha(pHP402) by chromatography on DEAE-Sepharose, Phenyl-Sepharose, Mono-Q, and Superose 6 resins. Fractions containing a catalytically inactive apoenzyme were identified by an enzyme-linked immunosorbent assay (ELISA) by using antisera to native UreA (29.5 kDa) and UreB (66 kDa). Purified recombinant urease was indistinguishable from native enzyme on a Superose 6 column and on Coomassie blue-stained sodium dodecyl sulfate-polyacrylamide gels. The protein reacted specifically on Western blots (immunoblots) with anti-UreA and anti-UreB antibodies and was recognized with an intensity equal to that of the native enzyme in an ELISA using human sera. Clones containing only ureA and ureB also produced an assembled but inactive enzyme. Enzyme activity was not restored by in trans complementation with cloned urease accessory gene sequences from Proteus mirabilis or Morganella morganii. H. pylori urease genes (ureCDAB) subcloned into pACYC184 were also not complemented with any of 1,000 cosmid clones containing H. pylori chromosomal sequences. However, larger clones containing 4.5 kb of DNA downstream of ureB synthesized catalytically active urease when grown in minimal medium. These data indicate that the ureA and ureB genes encoding H. pylori urease are transcribed and translated in E. coli and that these genes alone are sufficient for the synthesis and assembly of the native size enzyme. Genes downstream of ureB, however, are necessary for production of a catalytically active urease. PMID- 1612736 TI - Isolation and antigenicity of a 45-kilodalton Paracoccidioides brasiliensis immunodominant antigen. AB - In the present study, we analyzed human antibody responses to Paracoccidioides brasiliensis cellular antigens by the immunoblot technique to identify specific cellular components and to investigate the existence of antigen profile differences among serological responses of paracoccidioidomycosis (PCM) patients. Among the 64 PCM serum samples analyzed, a relatively homogeneous immunoglobulin G response to P. brasiliensis antigens was observed. The polypeptide with a mass of 45 kDa was the most clinically important, since antibody to this antigen was detectable in 90.6% of PCM patients studied and the six individuals who did not produce antibody were either at the end of treatment or in the posttherapy period and had shown clinical recovery. These facts suggested that the presence of this antibody may be an indicator of active disease. The 45-kDa antigen was also the most specific antigen of the PCM humoral immune response, since it reacted with only 2 of 79 (2.5%) heterologous serum samples tested: 1 histoplasmosis case and 1 tuberculosis case. This polypeptide was isolated from gels by electroelution and, when tested by an immunoradiometric assay and immunoblotting, maintained its reactivity with PCM sera and also with anti-P. brasiliensis polyclonal antibodies raised in rabbits at the same sensitivity levels as those obtained in immunoblotting with a crude antigen. Since in our assays the 45-kDa polypeptide was the major P. brasiliensis antigen and seemed to be specific for PCM, its use in alternative diagnostic methods is promising, especially in patients suspected of having the juvenile clinical form of PCM often associated with negative double immunodiffusion results. PMID- 1612737 TI - Sera of patients with high titers of immunoglobulin G against Toxoplasma gondii induce secretion of tumor necrosis factor alpha by human monocytes. AB - Toxoplasma gondii alone does not induce tumor necrosis factor alpha (TNF-alpha) secretion by human monocytes and macrophages. Nevertheless, sera from infected patients with high titers of specific immunoglobulin G antibodies against T. gondii induce TNF-alpha secretion, which is significantly higher than the corresponding induction by negative sera (P less than 0.05). After incubation with the positive serum, parasites also induce secretion of this cytokine, but TNF-alpha levels are lower (11.4 to 71.8%) than those obtained with positive serum alone. Therefore, this secretion seems to be elicited in part by antibody T. gondii complexes and/or another unidentified factor(s), probably different from lipopolysaccharide, interleukin-1, TNF-alpha, and gamma interferon. In this study, monocytes secreted more TNF-alpha into the culture fluid than macrophages did (P less than 0.05), and no correlation was observed between secretion of this cytokine by the monocytes and the intracellular multiplication of the parasites, evaluated by [3H]uracil incorporation. Sera from patients with other infections diseases did not induce secretion of TNF-alpha; however, serum free of antibodies to T. gondii, obtained from patients with leishmaniosis, also stimulated secretion of the cytokine. PMID- 1612738 TI - Immunoglobulin G2 confers protection against Borrelia burgdorferi infection in LSH hamsters. AB - We showed that immune serum and its immunoglobulin fractions, specifically immunoglobulin G2 (IgG2), could confer complete protection to irradiated hamsters challenged with the Lyme disease spirochete. Immune serum and its immunoglobulin fractions also killed Borrelia burgdorferi in vitro. Depletion of complement in vivo abrogated the ability of IgG2 to confer complete protection against B. burgdorferi. Furthermore, the majority of antibody reactivity directed against B. burgdorferi was found in the IgG2 fraction. These findings demonstrate that IgG2 plays an important role in acquired resistance against infection with B. burgdorferi. Additional studies are needed to determine the mechanism(s) by which B. burgdorferi evades host defenses despite the development of an effective borreliacidal antibody response. PMID- 1612739 TI - Capacity of listeriolysin O, streptolysin O, and perfringolysin O to mediate growth of Bacillus subtilis within mammalian cells. AB - The Listeria monocytogenes hemolysin listeriolysin O (LLO) plays a major role in mediating the escape of L. monocytogenes from a vacuolar compartment. In a previous report, it was shown that Bacillus subtilis expressing LLO could escape from a host vacuolar compartment and grow in the cytoplasm (J. Bielecki, P. Youngman, P. Connelly, and D. A. Portnoy, Nature [London] 345:175-176, 1990). In the present study, two related thiol-activated hemolysins, streptolysin O (SLO) and perfringolysin O (PFO), were expressed in B. subtilis and their ability to mediate intracellular growth was monitored by visual inspection and by assaying for CFU. Like LLO, PFO was active within the vacuolar environment, whereas SLO showed negligible activity. However, expression of PFO seemed to damage the host cells. The pH of the vacuole probably had little to do with these results, since all three hemolysins showed full or enhanced activity at pH 5.5, although LLO showed greatly reduced activity at pH 7. In addition, neutralization of the pH within host vacuoles by using weak bases had little effect on the lysis of the vacuole. The lack of SLO activity is probably caused by its lower specific activity; the purified protein had 10-fold less activity on a molar basis. These results suggest that LLO is not unique in its capacity to mediate intracellular growth of B. subtilis. PMID- 1612740 TI - Molecular cloning and expression of ptxA, the gene encoding the 120-kilodalton cytotoxin of Actinobacillus pleuropneumoniae serotype 2. AB - The genetic determinants of the 120-kDa cytotoxin of Actinobacillus pleuropneumoniae serotype 2 were isolated from a lambda DNA library by a plaque immunoblot technique. Expression of the 120-kDa polypeptide was confirmed by Western immunoblot analysis of infected Escherichia coli cell lysates, which were shown to be toxic for porcine alveolar macrophages in vitro. The genetic determinants of the toxin were subcloned into the plasmid vector pUC18. This plasmid (pPTX1) directed the synthesis and secretion of the active 120-kDa cytotoxin in E. coli. The recombinant toxin was indistinguishable from native cytotoxin from A. pleuropneumoniae serotype 2 with respect to molecular size, reaction in Western blot analysis, heat lability, cytotoxic activity, and neutralization by serum antibody. A restriction endonuclease cleavage map of pPTX1 was prepared, and deletion mutants were used to locate the minimal region of DNA required for production of intracellular toxin; this gene was termed ptxA. Southern hybridization analysis with a 1.7-kb PvuII fragment located within the ptxA gene revealed sequences with a high degree of homology in serotype reference strains 2, 3, 4, 6, and 8. Other reference strains did not contain sequences that were recognized by this probe. However, related sequences (greater than 71% homology) were detected in Actinobacillus actinomycetemcomitans and A. equuli. Weak hybridization was observed between the ptxA probe and pLKT5, which carries the lktAC genes of Pasteurella haemolytica, and between the ptxA probe and pAPH1, which carries the structural gene for type II hemolysin from A. pleuropneumoniae. The isolation of the genetic determinants of this cytotoxin will enable investigations of the structure and organization of the ptx DNA region and further analysis of its role in the pathogenesis of pleuropneumonia. PMID- 1612741 TI - Penetration of host cells by Rickettsia rickettsii appears to be mediated by a phospholipase of rickettsial origin. AB - Internalization of obligate intracellular bacteria belonging to the genus Rickettsia by eukaryotic cells requires participation of both the parasitized host and the microorganism. The term "induced phagocytosis" has been used specifically to describe the entry of Rickettsia prowazekii, although a similar mechanism is likely for R. rickettsii. A role for a phospholipase in the internalization process has been proposed for both of these organisms, with the strongest supporting evidence provided for R. prowazekii. Despite general acceptance of the notion that phospholipase activity is involved in the internalization process of these bacteria, the origin of the enzyme is not known. The results of the study presented here, which used R. rickettsii and Vero cells, suggest that a rickettsial phospholipase, rather than a host cell phospholipase, mediates internalization of the organism. This conclusion is based upon results which show that pretreatment of R. rickettsii, but not of host cells, with a specific chemical inhibitor of phospholipase, and also antiserum to this enzyme, significantly reduces uptake of the organism and its ability to cause plaque formation. PMID- 1612742 TI - Characterization of the Shigella serotype D (S. sonnei) O polysaccharide and the enterobacterial R1 lipopolysaccharide core by use of mouse monoclonal antibodies. AB - In the course of developing a live vaccine, we generated three murine monoclonal antibodies (MAb) specific for Shigella sonnei. The specificities of these MAb were determined by enzyme-linked immunosorbent assay and immunoblot analyses with whole cells or purified lipopolysaccharides (LPSs) as antigens. Two of them are specific for the Shigella serotype D O-polysaccharide determinant, whereas one specifically binds to the core hexose region of R1-type LPSs. With these MAb, it was possible to analyze clinical isolates and a hybrid Salmonella typhi strain for their expression of the corresponding LPS moieties. In addition to their use in the screening of candidate vaccine strains, the new MAb provide a powerful tool for epidemiological and phylogenetic studies of natural enterobacterial populations. PMID- 1612744 TI - Legionella pneumophila lipopolysaccharide activates the classical complement pathway. AB - Legionella pneumophila is a gram-negative bacterium capable of entering and growing in alveolar macrophages and monocytes. Complement and complement receptors are important in the uptake of L. pneumophila by human mononuclear phagocytes. The surface molecules of L. pneumophila that activate the complement system are unknown. To identify these factors, we investigated the effects of L. pneumophila lipopolysaccharide (LPS) on the classical and alternative complement pathways of normal human serum by functional hemolytic assays. Although incubation of LPS in normal human serum at 37 degrees C resulted in the activation of both pathways, complement activation proceeded primarily through the classical pathway. Activation of the classical pathway by LPS was dependent on natural antibodies of the immunoglobulin M class that were present in various quantities in sera from different normal individuals but were absent in an immunoglobulin-deficient serum obtained from an agammaglobulinemic patient. Additional studies using sheep erythrocytes coated with LPS suggested that the antibodies recognized antigenic sites in the carbohydrate portion of LPS. The ability of LPS to interact with the complement system suggests a role for LPS in the uptake of L. pneumophila by mononuclear phagocytes. PMID- 1612745 TI - Cross-reacting serum opsonins in patients with meningococcal disease. AB - We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence. A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera. Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence. The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes. PMID- 1612743 TI - Salmonella choleraesuis and Salmonella typhimurium associated with liver cells after intravenous inoculation of rats are localized mainly in Kupffer cells and multiply intracellularly. AB - Male Sprague-Dawley rats were inoculated intravenously with Salmonella choleraesuis or Salmonella typhimurium and used over 3 consecutive days to produce highly enriched (greater than 95% homogenous) preparations of Kupffer and mononuclear cells (KC), liver endothelial cells (LEC), and hepatocytes. The methods involved collagenase perfusion of the liver in situ, differential centrifugation of liver cells over a Percoll gradient, and selective attachment of the cells to plastic or to culture dishes coated with collagen. The different cell preparations were then assayed for the number and location, intracellular or extracellular, of associated viable bacteria. Most of the viable bacteria recovered were associated with KC and were mainly intracellular. The intracellular bacteria in KC from rats infected with either bacterial strain increased about 20- to 50-fold over 2 days. Some of the bacteria associated with LEC and in some experiments with hepatocytes also survived treatment with gentamicin and increased in number with time. Intracellular bacteria were readily visualized in KC by light microscopy and transmission electron microscopy. On rare occasions, bacteria were seen within LEC from rats infected with S. choleraesuis but not from those infected with S. typhimurium. Microcolonies of S. typhimurium but not of S. choleraesuis were occasionally found on the surface of some LEC. Bacteria were not seen within or on the surface of hepatocytes by transmission or scanning electron microscopy. The integration of microscopic and viability data suggested that most intracellular S. choleraesuis organisms in KC had been killed whereas most intracellular S. typhimurium organisms were viable. PMID- 1612746 TI - Comparison of adherence of Pseudomonas aeruginosa to respiratory epithelial cells from cystic fibrosis patients and healthy subjects. AB - The adherence of Pseudomonas aeruginosa PAO1 to primary cultures of cystic fibrosis nasal polyp (CFNP), normal human nasal polyp (NHNP), and immortalized CF and normal cell lines was studied. PAO1 bound significantly more to primary CFNP cells than to NHNP cells as the mean adherence +/- standard deviation of 5 x 10(7) CFU of 35S-labeled bacteria per ml per well was 15.09 x 10(6) +/- 4.25 x 10(6) CFU/ml per well and 7.62 x 10(6) +/- 2.11 x 10(6) CFU/ml per well, respectively (Mann-Whitney U test, P less than 0.0001). There was no significant difference in PAO1 adherence to the immortalized CF and normal cell lines. The primary CFNP cells had more receptors (115 per cell) than did NHNP cells (34 per cell). P. aeruginosa binding to CFNP was blocked by GlcNAc, NeuAc, L-Fuc, and D Gal, while binding to NHNP was blocked only by GlcNAc, suggesting that receptors on the two cell types were qualitatively different. Pseudomonas supernatants containing protease, phospholipase C, and neuraminidase activity increased adherence to CFNP and NHNP cells. The Pseudomonas exoproducts modified epithelial cell glycoconjugates, as characterized by binding of fluorescein isothiocyanate labeled lectins and the release of sialic acid. There was minimal release of fibronectin by the bacterial supernatants. The affinity of P. aeruginosa for CF epithelial cells appeared to be due to an increased number of receptors and modification of the epithelial cell surface by P. aeruginosa exoproducts that exposed asialoganglioside binding sites. PMID- 1612747 TI - Construction of a recombinant oral vaccine against Salmonella typhi and Salmonella typhimurium. AB - The viaB gene coding for the Vi antigen of Salmonella typhi Ty2 was subcloned into expression vector pYA248. The recombinant plasmid was termed SMM202 and transformed into Salmonella typhimurium chi 4072, an attenuated delta cya delta crp mutant. Recombinant S. typimurium Vi4072 had the ability to produce Vi capsular polysaccharide and also to invade and colonize the small intestine, mesenteric lymph nodes, and spleen of BALB/c mice. Mice orally immunized with Vi4072 developed serum and secretory antibody responses to the Vi antigen, as measured by a passive hemagglutination assay. Mice developed a delayed-type hypersensitivity following a footpad injection with Vi antigen after being sensitized orally with a suitable dose of Vi4072. Immunization of mice with Vi4072 afforded complete protection against fatal infection with virulent S. typhi Ty2. All data indicate that this route of antigen delivery is effective for stimulating antibody-mediated immunity and for inducing a cell-mediated immune response in BALB/c mice. Thus, S. typhimurium Vi4072 may serve as a vaccine for protection against typhoid fever and salmonellosis caused by S. typhimurium. PMID- 1612749 TI - Mycobacterial induction of activated killer cells: possible role of tyrosine kinase activity in interleukin-2 receptor alpha expression. AB - Mycobacterium avium is an intracellular opportunistic pathogen commonly seen in AIDS patients. M. avium-infected monocytes have been recently shown to be lysed by interleukin-2 (IL-2)-activated killer cells. Since some bacterial products can directly augment natural killer activity, we examined the ability of these microorganisms to induce killer cell activity. Coculture of M. avium with large granular lymphocytes (LGL) was found to augment the ability of LGL to lyse both tumor cells and bacterially infected autologous monocytes. The induction of tumoricidal activity by M. avium was only partially neutralized by the presence of anti-IL-2 antibodies, indicating that both IL-2-dependent and IL-2-independent mechanisms are responsible for activation of killer cells. Furthermore, only the direct interaction between bacterium and LGL could induce the expression of both IL-2 receptor alpha protein and mRNA, an effect which was abrogated by the presence of genistein, a tyrosine kinase inhibitor. Thus, M. avium was seen to induce killer cells, an activity that is concomitant with the up-regulation of IL 2 receptor alpha, or Tac antigen, expression and which involves signal transduction mechanisms mediated by tyrosine kinase activity. PMID- 1612750 TI - Role of the bacterial cell wall in middle ear inflammation caused by Streptococcus pneumoniae. AB - The pathogenesis of middle ear inflammation caused by Streptococcus pneumoniae was explored in the chinchilla model with different pneumococcal cell wall (CW) preparations, including isolated native CW, M1 muramidase CW (M1-CW) digest, amidase CW digest, and M1 peptidoglycan (M1-PG) digest. Inflammatory cell and lysozyme concentrations in middle ear fluid (MEF) were measured between 6 and 72 h after the middle ears were inoculated with one of the preparations or sterile saline. Middle ear histopathology was measured quantitatively at 72 h. Native CW, M1-CW digest, and amidase-CW digest caused significantly more inflammatory cell influx and lysozyme accumulation in MEF than saline did. M1-PG digest also caused more inflammatory cell influx and lysozyme accumulation in MEF than saline did but caused less inflammation than native CW or either CW digest. Epithelial metaplasia was significantly greater in ears inoculated with native CW than in ears inoculated with the CW or PG digest or with saline. Pneumococcal CW is, therefore, the principal factor that initiates middle ear inflammation in acute pneumococcal otitis media, and CW teichoication seems to be important in initiating this response. PMID- 1612748 TI - Interleukin-8 in sepsis: relation to shock and inflammatory mediators. AB - Because of its neutrophil-activating properties, interleukin-8 (IL-8) may play an important role in the pathophysiology of sepsis. We measured circulating IL-8 levels in 47 patients with clinical sepsis. Levels on admission were elevated in 42 of the 47 patients (89%) and were comparable in patients with gram-positive or gram-negative infections. Patients with shock had significantly higher IL-8 levels than normotensive patients (P = 0.0014, Wilcoxon-Mann-Whitney test), whereas no differences in IL-8 levels were found between patients with or without adult respiratory distress syndrome. Patients who died had higher IL-8 levels on admission than the patients who survived. The largest differences in IL-8 levels between survivors and nonsurvivors was found when only patients with positive cultures were considered (P = 0.0342). IL-8 levels appeared to correlate significantly with lactate levels and inversely with leukocyte and platelet numbers and mean arterial pressure. In addition, the IL-8 level in the sepsis patients was found to correlate significantly with levels of IL-6, elastase-alpha 1-antitrypsin, and C3a. Serial observations revealed that in most patients IL-8 levels decreased, irrespective of the outcome. Thus, our results demonstrate that IL-8 levels are increased in most patients with sepsis and correlate with some important clinical, biochemical, and inflammatory parameters. These findings suggest a role for IL-8 in the pathophysiology of sepsis. PMID- 1612751 TI - Humoral and cell-mediated immunity in mice to a 17-kilodalton lipoprotein of Francisella tularensis expressed by Salmonella typhimurium. AB - A 17-kDa lipoprotein, TUL4, of the facultative intracellular bacterium Francisella tularensis is one of several membrane proteins that induce an in vitro response in T cells from F. tularensis-primed humans. A DNA fragment of the live vaccine strain F. tularensis LVS encoding TUL4 was cloned into Salmonella typhimurium chi 4072, an attenuated delta cya delta crp mutant. Expression of the protein by the recombinant S. typhimurium chi 4072 (pTUL4-15) was maintained after passage in BALB/cJ mice. When mice were immunized with S. typhimurium chi 4072(pTUL4-15), some animals showed an antibody response and a T-cell response to TUL4. When the immunized mice were challenged with the live vaccine strain F. tularensis LVS, bacterial counts in the liver and spleen were lower than in animals immunized with S. typhimurium chi 4072. Immunization with F. tularensis LVS caused a much stronger protection against the challenge than did immunization with S. typhimurium chi 4072(pTUL4-15). The present study demonstrated that the 17-kDa lipoprotein TUL4 of F. tularensis is involved in a protective immunity to tularemia. Possibly, several T-cell-reactive proteins of the organism have to contribute for optimal protection to be achieved. PMID- 1612752 TI - Construction of Cu-Zn superoxide dismutase deletion mutants of Brucella abortus: analysis of survival in vitro in epithelial and phagocytic cells and in vivo in mice. AB - Cu-Zn superoxide dismutase (SOD) deletion mutants of Brucella abortus S2308, a virulent strain, and S19, a vaccine strain, were generated by gene replacement. A deletion plasmid, pBA delta sodknr, was constructed by excising the Cu-Zn SOD gene (Cu-Zn sod) from a 2.3-kb B. abortus DNA fragment of plasmid pBA20-1527 and inserting a 1.4-kb DNA fragment encoding kanamycin resistance into the Cu-Zn sod excision site. The deletion plasmid was introduced into B. abortus by electroporation, and Southern blot analysis confirmed that the antibiotic resistance fragment had replaced Cu-Zn sod in kanamycin-resistant colonies. The survival and growth of Cu-Zn SOD mutant strains were compared with that of the parental strains in HeLa cells and in the mouse macrophagelike cell line J774. The survival and growth of the Cu-Zn SOD mutant strains were similar to those of their respective parental strains in HeLa and J774 cell lines. The kinetics of infection with these strains were examined in BALB/c mice. The splenic levels of the S19 Cu-Zn SOD mutant recovered from intraperitoneally infected BALB/c mice were approximately 10-fold lower than those of the parental strain through 26 days postinfection. Thereafter, infection sharply declined in both groups, and by 105 days postinfection, no organisms were detected. The splenic levels of the S2308 Cu-Zn SOD mutant were lower than those of wild-type S2308-infected mice. The spleen weights of mice infected with the S2308 Cu-Zn SOD mutant were consistently lower than those of wild-type S2308-infected mice. These results suggest that the antioxidant enzyme Cu-Zn SOD plays a role in the survival and pathogenicity of B. abortus in vivo. PMID- 1612753 TI - Cholera toxin as a mucosal adjuvant: effects of H-2 major histocompatibility complex and lps genes. AB - In previous studies we found that cholera toxin (CT) can act as a mucosal adjuvant; i.e., it can stimulate an intestinal secretory immunoglobulin A (S-IgA) response to an unrelated protein antigen when both are fed together to mice. The purpose of this study was to determine whether the mucosal adjuvanticity of CT is restricted by either H-2 major histocompatibility complex or lps genes by using congenic inbred strains that differ at only a single genetic locus. Groups of five mice each were fed saline, CT (10 micrograms), keyhole limpet hemocyanin (KLH) (5 mg), or both CT and KLH on four different days, and samples of intestinal secretions and plasma were obtained 1 week after the last feeding. In the mice fed both CT and KLH, the intestinal S-IgA anti-KLH response was higher in H-2b congenic strains than in H-2k congenic strains, and in addition there was a highly significant positive correlation between the intestinal S-IgA anti-KLH and S-IgA anti-CT responses in the intestinal secretions of individual mice. Similarly, in the lps congenic strains, mice of the endotoxin-responsive strain that were fed both CT and KLH had substantially higher S-IgA and plasma IgG responses to KLH than did mice of the endotoxin-unresponsive strain. The effect of CT on the induction of oral tolerance to KLH in the H-2 congenic strains was also examined. In contrast to the results above, the abrogation of oral tolerance to KLH by CT occurred in all strains regardless of H-2 haplotype. Similarly, the adjuvant effect of CT on plasma IgG anti-KLH responses after both were given together intraperitoneally was not restricted by H-2. I conclude that the mucosal adjuvanticity of CT is influenced by both the H-2 and lps genetic loci and that it appears to depend on a vigorous mucosal immune response to CT itself. PMID- 1612755 TI - Immunogenicity and antigenic heterogeneity of a human transferrin-binding protein in Neisseria meningitidis. AB - Growing Neisseria meningitidis on an iron restriction medium induces the synthesis of new outer membrane proteins, some of them true iron-regulated outer membrane proteins (IROMPs) and others synthesized because of the stress produced by the iron restriction. Some of these proteins are antigenic and can be considered for the development of vaccines; this is especially desirable in the case of N. meningitidis serogroup B, for which polysaccharide vaccines are not efficient. The antigenicity of N. meningitidis 37- and 70-kDa IROMPs has been studied previously; in this work, we studied the immunogenicity and antigenic heterogeneity of another IROMP, the human transferrin-binding protein 2 (TBP2), which seems to be indispensable for meningococcal growth inside the host. Mice were inoculated with purified outer membrane vesicles (blebs) from 5 selected N. meningitidis strains, and the five serum samples obtained were analyzed for anti TBP2 antibodies by using the homologous strain and for cross-reactivity with the TBP2 of the 4 other selected strains and another 35 heterologous N. meningitidis strains. The TBP2s of the 5 strains tested were all immunogenic in mice to various degrees depending on the strain, and all five TBP2s shared one or more epitopes with heterologous strains (as shown by the cross-reactivities of the five serum samples), although the number of cross-reacting strains was very variable, ranging from 2 for strain V002 to 35 for strain P391. This suggests that the TBP2 epitopes of different strains differ in nature or in their accessibility to the immune system. Under the iron restriction conditions used, all strains synthesized a non-TBP2 antigenic 56-kDa protein thought to be a stress protein. PMID- 1612754 TI - Spleen cell cytokine secretion in Mycobacterium bovis BCG-infected mice. AB - Three susceptible mouse strains, i.e., BALB/c (H-2d), C57BL/6 (H-2b), and major histocompatibility complex-congenic BALB.B10 (H-2b), were infected intravenously with 4 x 10(6) CFU of live Mycobacterium bovis BCG and analyzed 4 weeks later for in vitro spleen cell cytokine secretion in response to purified protein derivative (PPD), BCG culture filtrate (CF), BCG cellular extract, total BCG, the purified extracellular 30-32-kDa antigen (the fibronectin-binding antigen 85), or the intracellular 65-kDa heat shock protein. C57BL/6 and BALB.B10 mice produced 5 to 10-fold more gamma interferon and interleukin-2 (IL-2) when stimulated with CF, PPD, and antigen 85 than BALB/c mice did. When stimulated with BCG extract and whole BCG, gamma interferon and IL-2 levels were generally lower and comparable in the three strains. IL-4 was detected in spleen cell culture supernatants from infected BALB/c mice but not from C57BL/6 or BALB.B10 mice. IL 5 could not be detected. C57BL/6 and BALB.B10 spleen cells also produced more tumor necrosis factor alpha and IL-6 after stimulation with PPD and CF than BALB/c cells did. Finally, BCG vaccination generated efficient protective immunity in C57BL/6 and BALB.B10 mice but not in BALB/c mice. These data suggest that secreted mycobacterial CF antigens selectively induce a strong TH1 response in BCG-infected C57BL/6 and BALB.B10 mice, whereas in BALB/c mice this response is partly counterbalanced by TH2 cells. PMID- 1612756 TI - Rational attenuation of Corynebacterium pseudotuberculosis: potential cheesy gland vaccine and live delivery vehicle. AB - The phospholipase D (PLD) gene (pld) has been deleted from the Corynebacterium pseudotuberculosis chromosome by using site-specific mutagenesis. Sheep infection trials indicate that the PLD-negative C. pseudotuberculosis strain (Toxminus) is incapable of inducing caseous lymphadentis (cheesy gland) even at doses two logs higher than that at which the wild-type strain produces the disease. This clearly establishes PLD as a major C. pseudotuberculosis virulence factor. Vaccination of sheep with live Toxminus C. pseudotuberculosis elicits strong humoral and cell mediated immune responses and protects the animals from wild-type challenge. PMID- 1612758 TI - Interaction of Mycoplasma dispar with bovine alveolar macrophages. AB - The capacity to avoid phagocytosis and the activation of bovine alveolar macrophages (BAM) by encapsulated Mycoplasma dispar or purified M. dispar capsule was investigated. Encapsulated and unencapsulated M. dispar were cocultured with BAM in the presence or absence of antisera prepared against unencapsulated M. dispar or purified capsule antiserum. Unopsonized mycoplasmas resisted phagocytosis, while only anti-capsule antibodies enhanced the phagocytosis of encapsulated mycoplasmas. BAM were cultured in the presence of purified M. dispar capsule or either live or heat-killed encapsulated or unencapsulated M. dispar. These BAM were then activated with Escherichia coli endotoxin or left without further activation. The supernatants of these cultures were assayed for tumor necrosis factor, interleukin 1, and glucose consumption as indicators of macrophage activation. Tumor necrosis factor and interleukin 1 were produced by BAM stimulated with unencapsulated M. dispar but not when encapsulated M. dispar or its purified capsule was used. Similarly, glucose consumption was increased in the presence of unencapsulated M. dispar, but not when BAM were cocultured with encapsulated M. dispar or purified capsule. When BAM were treated with purified capsule or encapsulated mycoplasmas, they could not be subsequently activated by endotoxin. These results indicate that encapsulated M. dispar or purified capsule exerts an inhibitory effect on the activity of BAM and prevents the activation of these cells. PMID- 1612757 TI - Localization and biochemical characterization of the ORF6 gene product of the Mycoplasma pneumoniae P1 operon. AB - ORF6 represents one of the two open reading frames flanking the P1 attachment protein gene of Mycoplasma pneumoniae in the order ORF4-P1-ORF6 (J.M. Inamine, T.P. Denny, S. Loechel, U. Schaper, C.H. Huang, K.F. Bott, and P.C. Hu, Gene 64:217-219, 1988; J.M. Inamine, S. Loechel, and P.C. Hu, Gene 73:175-183, 1988; C.J. Su, V.V. Tryon, and J.B. Baseman, Infect. Immun. 55:3023-3029, 1987), indicating an operonlike organization. As described previously, we identified two proteins with molecular masses of 40 and 90 kDa (B. Sperker, P.C. Hu, and R. Herrmann, Mol. Microbiol. 5:299-306, 1991) which might represent two cotranslational cleavage fragments of the ORF6 gene product. To determine the site of the putative cotranslational cleavage, the first 10 amino acids of the N terminus of the isolated 90-kDa protein were sequenced. The data are consistent with the DNA-deduced amino acid sequence between amino acid positions 455 and 465 (RAGNSSETDAL). Thus, the cleavage site was identified at amino acid position 455 (R). In this study, the two proteins were localized and biochemically characterized. Both proteins are part of the insoluble fraction of M. pneumoniae as shown by immunoblots of supernatants and pellets of mechanically disrupted cells subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS PAGE). Surface proteolysis followed by SDS-PAGE and Western blot (immunoblot) analysis, covalent labelling of surface-exposed proteins with [125I]iodide and subsequent immunoprecipitation of both radiolabelled proteins, immunofluorescence studies with formalized and living M. pneumoniae, and immunoadsorption experiments provided strong evidence that the 40- and 90-kDa proteins are membrane-associated proteins expressing surface-exposed regions. PMID- 1612759 TI - Cloning and DNA sequence analysis of a Serpulina (Treponema) hyodysenteriae gene encoding a periplasmic flagellar sheath protein. AB - A Serpulina (Treponema) hyodysenteriae expression library was constructed in vector lambda ZAP and screened with a polyclonal antiserum raised against S. hyodysenteriae periplasmic flagella. A single immunoreactive plaque was chosen for further analysis. The recombinant phage from this plaque contained a gene encoding the 44-kDa protein that is on the outer layer (or sheath) of the periplasmic flagella. DNA sequence analysis showed that the gene encodes a protein of 320 amino acids. The protein is homologous to the flagellar sheath proteins of Treponema pallidum and Spirochaeta aurantia but not to any other flagellar proteins. We designated the cloned S. hyodysenteriae flagellar sheath protein gene flaA and the encoded protein FlaA. The 19 N-terminal amino acid residues of FlaA constitute a signal peptide that is cleaved from the protein before assembly onto the flagella in the periplasm. Amino acid residues 20 to 38 correspond to the N-terminal amino acid sequence of the native protein. Upstream from the gene, DNA motifs that are similar to the consensus Escherichia coli -35 and -10 promoter sequences and a ribosome binding site were identified. Downstream from the gene, two inverted repeat sequences that may serve as a rho independent transcription termination signal are present. PMID- 1612760 TI - Infection-induced airway fibrosis in two rat strains with differential susceptibility. AB - Chronic infections play a significant role in the morbidity and mortality of patients with chronic airflow limitation. By stimulating airway inflammation, persistent infection has the potential to cause airway fibrosis. However, in patient this condition is most typically found in lungs damaged by other factors, such as smoking, abnormal secretions, or barotrauma. We report the characterization of Mycoplasma pulmonis infection-induced lung fibrosis in two immunocompetent rat strains with no preexisting lung disease. The fibrosis was predominantly in the airways, as demonstrated by the findings for infected animals of increased airway inflammation, airway fibrosis, and airway wall thickness, which correlated with the collagen content of the lungs. Also, the physiological alterations were the opposite of those found in interstitial fibrosis, with a positive correlation between lung compliance and collagen content. The airway fibrosis was noted earlier and to a greater extent in Lewis rats than in Fisher rats, and this result apparently was related to regulation of the inflammatory response. Airway wall thickness, airway inflammation, and airway fibrosis are commonly reported in tissue specimens from patients with chronic airway diseases and have been shown to correlate with airflow limitation in patients with chronic obstructive pulmonary disease. Thus, this model may be useful in furthering our understanding of the role of chronic infection and airway inflammation in airflow obstruction. PMID- 1612761 TI - Phenotypic phase variation in Haemophilus somnus lipooligosaccharide during bovine pneumonia and after in vitro passage. AB - A high rate of phenotypic variation in the lipooligosaccharide (LOS) electrophoretic profile of Haemophilus somnus occurred in most isolates obtained at approximately weekly intervals from three calves intrabronchially challenged with a cloned isolate of H. somnus 2336. Daily subculturing for 2 weeks resulted in at least one major alteration in the LOS electrophoretic profiles for strain 2336 and both additional disease isolates examined, but no change occurred in the LOS electrophoretic profiles for any of three commensal isolates examined. None of the LOSs from any of the postchallenge intrabronchial isolates reacted with rabbit antiserum to the challenge strain LOS in immunoblotting, but LOSs from two nasopharyngeal isolates did. Antigenic variation in the extracted LOSs of most of the isolates was supported by the results of an enzyme-linked immunosorbent assay. Preimmune serum from each of the calves did not react with any of the isolates or the challenge strain, whereas sera obtained 35 days after challenge reacted with the challenge strain and zero to five additional isolates and sera obtained 74 days after challenge reacted with two to six additional isolates. Recognition of LOSs from isolates obtained near the end of the 70-day experiment by day-74 sera was related to clearance of the bacteria from the lungs. Isolates demonstrating major electrophoretic changes showed variations in the composition of the oligosaccharide, but not lipid A, moiety of their LOSs. The oligosaccharide of the LOS of each isolate was composed predominantly of glucose but varied substantially in the contents of galactose, arabinose, xylose, mannose, and 3-deoxy-D-manno-octulosonic acid. Therefore, the LOS of H. somnus is capable of undergoing compositional and antigenic variations, which may act as an important virulence mechanism for evading host immune defense mechanisms. PMID- 1612762 TI - Histopathological and serological progression of experimental Staphylococcus aureus arthritis. AB - In a newly developed mouse model of Staphylococcus aureus arthritis the kinetics of joint destruction and serological manifestations as well as the clinical course of arthritis and osteitis were studied. Almost all mice developed histopathological signs of arthritis upon a single intravenous injection of 10(7) S. aureus LS-1 cells. There was rapid joint destruction, with synovial hypertrophy already visible, within 24 h after injection of the bacteria. Cartilage and/or bone erosions were seen in a majority of the mice within 72 h. Extra-articular manifestations, especially signs of bone infection, were also found soon after inoculation of the bacteria. Tail osteitis was frequent (50% of the mice) but appeared later than arthritis. Polymorphonuclear cells prevailed in the early joint lesions and were also common in the extra-articular manifestations. Within 3 days, mononuclear cells were also seen in the inflamed synovium, gaining a dominant position 3 weeks after the start of the disease. Serum interleukin-6 levels were already increased within 6 h after bacterial injection and remained elevated throughout the course of arthritis. Serum tumor necrosis factor levels were increased within 24 h. There was a tremendous induction of immunoglobulin production, especially of the immunoglobulin G1 isotype. This was paralleled by the production of specific antibodies to S. aureus (cell walls and toxin), as well as autoantibodies (rheumatoid factors and anti-single-stranded DNA antibodies), all predominantly of the immunoglobulin G isotype. The type and magnitude of the immunoglobulin G response together with the elevated interleukin-6 levels speak in favor of both antigen-specific and polyclonal B-cell activation during S. aureus arthritis. This study points out important similarities between our new model of S. aureus arthritis and human S. aureus arthritis. This resemblance will enable controlled studies of pathogenetic mechanisms of septic arthritis as well as therapeutic and prophylactic approaches. PMID- 1612763 TI - Evidence for in vivo expression of transferrin-binding proteins in Haemophilus influenzae type b. AB - Haemophilus influenzae type b acquires transferrin-bound iron via a siderophore independent mechanism involving direct contact between the human iron-binding glycoprotein and the bacterial cell surface. Evidence has accumulated to show that the transferrin receptor consists of at least two iron-regulated outer membrane transferrin-binding proteins (TBPs), of which one has a molecular mass of around 100 kDa (TBP1) and the other has a molecular mass of 60 to 90 kDa (TBP2). In H. influenzae type b strain Eagan, proteins of 76, 90, and 107 kDa appear to be involved in transferrin binding. To determine whether these TBPs are expressed during growth in vivo, strain Eagan was recovered without subculture from the intraperitoneal cavities of infected infant rats. By using a dot blot assay, outer membranes prepared from these in vivo-grown bacteria, unlike those grown in iron-sufficient broth, bound human transferrin and produced the 76-, 90 , and 107-kDa TBPs. Immunoblotting experiments using convalescent sera from infected rats also revealed the presence of antibodies to the 76- and 90-kDa strain Eagan TBPs. In addition, convalescent sera from three of four patients recovering from H. influenzae type b meningitis contained antibodies to the 90- and 105-kDa TBPs of the corresponding infecting strain. Furthermore, fresh clinical isolates of H. influenzae type b recovered from blood and cerebrospinal fluid showed constitutive expression of the TBPs, which became iron regulated only after prolonged in vitro subculture on iron-sufficient medium. This contrasted with the laboratory-adapted Eagan strain, in which the TBPs remained iron regulated even after animal passage. These findings indicate that the H. influenzae type b transferrin receptor is expressed during experimental animal and human infections. PMID- 1612764 TI - Interaction of ruminant transferrins with transferrin receptors in bovine isolates of Pasteurella haemolytica and Haemophilus somnus. AB - The interactions of ruminant transferrins with receptors on bovine isolates of Pasteurella haemolytica and Haemophilus somnus were compared by growth studies and direct and competitive binding assays. Isolates of P. haemolytica were capable of utilizing and binding transferrin from sheep, goat, or cattle, whereas isolates of H. somnus were capable of utilizing and binding only bovine transferrin. PMID- 1612766 TI - Phosphate starvation enhances expression of the immunodominant 38-kilodalton protein antigen of Mycobacterium tuberculosis: demonstration by immunogold electron microscopy. AB - In this work, we grew Mycobacterium tuberculosis in an enriched Proskauer-Beck Youmans culture medium in the presence and in the absence of phosphate salts. Immunoblot analysis of sonic extracts showed overexpression of the 38-kDa protein antigen by bacilli grown in the medium without phosphate. These observations were confirmed by immunogold electron microscopy, which showed that the number of gold particles was significantly higher in bacilli grown in medium without phosphate than in bacilli grown in medium with phosphate. The 38-kDa protein was located mainly in the wall and on the cell surface. PMID- 1612765 TI - Virulence-associated 15- to 17-kilodalton antigens in Rhodococcus equi: temperature-dependent expression and location of the antigens. AB - Virulent Rhodococcus equi showing 15- to 17-kDa antigens, which is virulent in mice, was found to harbor an 85-kbp plasmid, and the 15- to 17-kDa antigens were found to be associated with possession of the 85-kbp plasmid of R. equi (S. Takai, T. Sekizaki, T. Ozawa, T. Sugawara, Y. Watanabe, and S. Tsubaki, Infect. Immun. 59:4056-4060, 1991). The expression of these antigens was temperature regulated: when cells were grown at a low temperature (25 to 32 degrees C), they did not express them, whereas they expressed them in large amounts when the cells were grown at a higher temperature (34 to 41 degrees C). The antigens were expressed on the cell surface, as evidenced by their susceptibility to proteolysis by a trypsin and by the biotin-avidin protein-blotting technique. PMID- 1612767 TI - Morphological and biochemical study of cytoskeletal changes in cultured cells after extracellular application of Clostridium novyi alpha-toxin. AB - Clostridium novyi alpha-toxin caused retraction and rounding of cultured endothelial cells from porcine pulmonary arteries; nevertheless, the endothelial cells firmly adhered to their supports. F-actin stained with fluorescein-labeled phalloidin was condensed around the nucleus, whereas intermediate filaments and microtubules appeared unchanged. The content of F-actin and myosin was decreased, but that of G-actin or vimentin was not. A predominant role of the microfilament system in C. novyi alpha-toxin cytopathic action is suggested. PMID- 1612768 TI - Morphological changes of cultured endothelial cells after microinjection of toxins that act on the cytoskeleton. AB - Clostridium novyi alpha-toxin and C. difficile toxins A and B (all 200 to 300 kDa) and C. botulinum C2-I toxin (50 kDa) caused a delayed and persistent retraction and rounding of microinjected cells. Microinjected phalloidin acted fast and reversibly. Unlike C2-I toxin, phalloidin passed through the intercellular junctions. Specific antitoxin applied to the medium did not prevent the action of microinjected C. novyi or C. difficile toxin B. Microinjected antitoxin protected against the toxins applied with the medium or injected into the same cells. PMID- 1612769 TI - Survival of virulent and attenuated strains of Brucella abortus in normal and gamma interferon-activated murine peritoneal macrophages. AB - Virulent Brucella abortus 2308 was phagocytized more readily than attenuated strain 19 following opsonization and survived at significantly higher levels in normal murine peritoneal macrophages and in macrophages treated with gamma interferon. Activation of macrophages with gamma interferon greatly inhibited intracellular replication of strain 2308 but did not result in its elimination. These data support the hypothesis that persistent infection of the host requires the ability of antibody-opsonized B. abortus to survive in activated macrophages. PMID- 1612770 TI - Characterization of GP110, a neutrophil surface protein. AB - Localized juvenile periodontosis is associated with a defect of neutrophil chemotaxis that is characterized by selective depletion of a surface protein with a molecular mass of 110 kDa (GP110). Data on partial characterization of GP110 suggest that it is a glycoprotein which is enriched in Lys, Glu, His, Leu, and Ala residues. PMID- 1612771 TI - Further antigenic similarities of Neisseria gonorrhoeae lipooligosaccharides and human glycosphingolipids. AB - Anticarbohydrate monoclonal antibodies were tested for their ability to bind to various strains of Neisseria. A monoclonal antibody that binds to the ganglio series glycosphingolipid, ganglio-N-triaosylceramide, also bound to strains of Neisseria gonorrhoeae but not to other species of Neisseria. An antibody specific for the globo-series glycosphingolipid, globotriaosylceramide, also bound to strains of N. gonorrhoeae, Neisseria meningitidis, Neisseria lactamica, and Branhamella catarrhalis but not to any other strains of nonpathogenic Neisseria. PMID- 1612772 TI - Adhesion protein YadA of Yersinia species mediates binding of bacteria to fibronectin. AB - The interaction between fibronectin and Yersinia strains was studied. Wild-type Y. enterocolitica strains expressing the virulence-plasmid-encoded adhesion protein YadA adhered strongly to fibronectin-coated coverslips, while their plasmid-cured variants expressed weaker binding. The cloned yadA gene of Y. enterocolitica or Y. pseudotuberculosis conferred fibronectin-binding ability both to Escherichia coli and to Y. psuedotuberculosis strains lacking the YadA protein. The YadA protein did not mediate binding to isolated fragments of fibronectin or to soluble fibronectin. PMID- 1612773 TI - Menstrual and reproductive factors and breast cancer in women with family history of the disease. AB - The relationship between socio-economic indicators, body mass, reproductive and menstrual factors and risk of "familial" breast cancer has been analyzed using data from a large case-control study of breast cancer conducted in Italy. A total of 3,037 breast-cancer patients aged 75 years or less admitted to a network of hospitals in the Greater Milan area were interviewed. Controls were 2,569 women aged 75 or less, admitted for acute conditions to the same network of hospitals where cases had been identified. Women were not included as controls if they had been admitted for gynecological, hormonal or neoplastic diseases. A total of 331 cases and 121 controls reported a family history of breast cancer in their first degree relatives, with a family history tended to be more educated and of higher social class than controls with family history, but these differences were not statistically significant. No relationship emerged with marital status and body mass index. The estimated multivariate relative risks were, compared with nulliparous women, respectively 0.9, 1.2 and 1.2 for women reporting 1, 2 and 3 or more births. The risk of breast cancer was also greater in women reporting one or more spontaneous abortions: compared with those who did not, the estimated relative risk was 1.9 (95% confidence interval 0.8 to 3.7). Relative to women reporting their first birth below age 25, the estimated relative risks were 1.3 and 0.9 in those reporting it at age 25 to 29 and 30 or more respectively. Likewise, no consistent relationship emerged with lifelong menstrual pattern and menopausal status. These results suggest that menstrual and reproductive factors do not play an important role in the risk of breast cancer in women with a history of the disease in first-degree relatives. PMID- 1612774 TI - Appearance and detection of multiple copies of the mdr-1 gene in clinical samples of mammary carcinoma. AB - To examine the presence of multiple copies of the mdr-I gene in clinical tumor samples we have developed an approach where the cells are obtained by fine-needle biopsies and the number of gene copies determined by PCR. The temporal appearance of amplified mdr-I was examined in 20 breast-cancer patients with clinical stage IV disease receiving endocrine treatment. Tumor samples were obtained every 2nd to 3rd month from the same tumor lesion. None of the initial samples from each patient contained multiple copies of mdr-I. Of 16 patients who showed increased tumor size, 4 developed multiple gene copies, showing that the event occurs without cytotoxic selection of cells with chemotherapy. PMID- 1612775 TI - c-myc amplification is an independent prognostic factor in postmenopausal breast cancer. AB - The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes. PMID- 1612776 TI - Study of fibronectin and mRNA in human laryngeal and ectocervical carcinomas by in situ hybridization and image analysis. AB - The expression of fibronectin (FN) mRNA was studied in histological sections of surgical biopsies from human laryngeal and ectocervical invasive carcinomas of different grading stages by in situ hybridization and image analysis. This approach made it possible to identify the cell types synthesizing FN mRNA in the tissue sections and to compare semi-quantitatively the FN mRNA levels expressed in the different specimens. The carcinoma cells synthesized low levels of FN mRNA, comparable to those detected in control epithelia and connective-tissue fibroblasts. Well-differentiated (G1) laryngeal and ectocervical carcinomas induced the synthesis of FN mRNA--to levels 7 to 13 times higher than in control connective tissues--in the stromal fibroblasts surrounding the tumors. In carcinoma samples analysed, the amount of FN mRNA detected in the stroma decreased in relation to tumor grading (from G1 to G3) and the stromal destruction. FN mRNA was not detectable in the endothelial cells of venules while it was present in large amounts in those surrounding the capillaries present in the stroma. These data indicate that FN, usually observed around carcinomas, is produced by stromal fibroblasts, which are induced to express FN mRNA, presumably in response to diffusible factors produced by the tumor cells, and/or by endothelial cells of the infiltrating capillary vessels. The induction of FN mRNA, inversely proportional to the tumor grading, may be useful in evaluating the invasion potential of the tumor. PMID- 1612777 TI - The changing importance of prognostic factors in breast cancer during long-term follow-up. AB - A cohort of 464 breast-cancer patients were followed up for over 10 years and the clinical, histological and morphometric factors were related to survival within different time periods during follow-up. Tumor diameter, axillary lymph-node status (pN), tubule formation and the fraction of intraductal growth as determined from the primary tumor biopsy specimen had prognostic value up to 5 years. Histological grade, morphometric nuclear factors and the M/V index had only short-term prognostic value immediately after the primary therapy. In axillary lymph-node-negative (ANN) tumors tubule formation, intraductal growth, tumor necrosis and tumor diameter had prognostic value during the first 3 postoperative years. In axillary lymph-node-positive (ANP) tumors, tumor diameter, intraductal growth and tubule formation had long-term prognostic value whereas the M/V index had prognostic value only for 1 postoperative year. Tumor diameter, axillary lymph-node status, tubule formation and the proportion of intraductal growth also had independent long-term prognostic value in a multivariate analysis and accordingly these factors can categorize breast-cancer patients into prognostic groups after several years of follow-up. In contrast, mitotic frequency loses its prognostic power within 2 postoperative years, while morphometric nuclear factors and histological grade have no practical prognostic value after 1 year of follow-up. PMID- 1612778 TI - Risk factors for gallbladder cancer: a Polish case-control study. AB - A population-based case-control study of gallbladder cancer was conducted in the south-west of Poland, within the frame-work of the SEARCH Programme of the International Agency for Research on Cancer. A total of 73 cases and 186 controls were interviewed using a questionnaire including demographic and socio-economic factors, education, smoking, alcohol, tea and coffee consumption, and past medical history. A validated diet history was used to estimate the daily intake of calories, fats, carbohydrates, proteins, cholesterol, fibres and vitamins C and E. Gallbladder disease was the major determinant of subsequent gallbladder cancer: 41 cases (56%) vs. 15 (8%) controls had a past history of gallbladder disease, corresponding to an odds ratio (OR) of 12.5 (95% confidence interval, 5.8 to 26.6), and the OR was 12.1 for gallbladder problems dating back 20 years or more in the past. There was an inverse relationship with education, the OR being 0.3 (95% CI 0.1 to 1.2) for 13 years of education or more vs. less than 7. Gallbladder cancer risk was positively associated with total calorie intake, with ORs of 1.4, 1.5, 4.1 for the 3 upper quartiles compared with the lowest one (trend, p less than 0.01). Weaker direct associations were observed for proteins, carbohydrates and cholesterol. There was some suggestion of inverse associations with fibre intake, and a more consistent one with vitamins C and E. These results further quantify the role of gallstones, and suggest that total calorie intake and other dietary factors potentially linked with benign gallbladder conditions are involved in the aetiology of gallbladder cancer. PMID- 1612779 TI - Cytostatic activity of new synthetic anti-tumor aza-alkyllysophospholipids. AB - Alkyllysophospholipids are analogues of the naturally occurring 2 lysophosphatidylcholine which have been reported to have selective in vitro/in vivo anti-tumor activity. Their antiproliferative effect has been found against a variety of animal and human tumor cell lines. We have characterized the cytostatic activity of 2 newly synthetized aza-alkyllysophospholipids (AALPs), the BN52205 and the BN52211, on a human tumor cell line derived from a colon adenocarcinoma, the HT29. We used 3 different flow cytometric approaches to study which phase of the cell cycle was the most sensitive to the antiproliferative activity of the 2 AALPs. By applying the biparametric analysis of 5'-bromo-2 deoxyuridine incorporation vs. DNA content we have been able to demonstrate that the 2 AALPs do not interfere with the S phase of the cell cycle. The simultaneous measurement of total nuclear protein vs. DNA content in isolated HT29 nuclei enabled us to exclude a block in the M phase of the cell cycle. Finally, stathmokinetic analysis enabled us to show that cytostatic activity of the 2 new AALPs is characterized by multiple "terminal points" as the drugs' action results in a G1 block, in a slow-down of the transition from late S to G2 followed by an accumulation of HT29 cells in the G2 phase of the cell cycle. PMID- 1612780 TI - Two antigens detected on human ocular melanomas with the mouse monoclonal antibodies 2/10SN and 10/12SN. AB - Seven human ocular melanoma cell lines were established in vitro and 3 of these, GU-4, LLN-40 and its subline C17-11, were characterized. Mice were immunized with these ocular melanoma cell lines, and 2 hybridomas producing monoclonal IgG1 antibodies (MAb) were produced. MAb 2/10SN recognizes a 44-kDa monomeric protein, whereas MAb 10/12SN reacts with an 83/65-kDa heterodimeric protein. These melanoma-associated antigens (MAA) are detected at high concentrations in the cytoplasm of ocular melanoma cells. However, cell-surface labelling techniques suggest that these MAA are also associated with the cell-surface membrane. These 2 ocular MAA are also expressed by several skin melanoma cell lines. Immunohistochemical studies have localized these antigens to ocular and skin melanomas, to sweat ducts and basal squamous cells in normal skin, with limited expression in several other normal tissues and some carcinomas. Biodistribution studies in nude mice with human ocular melanomas have demonstrated good localization of 125I-labeled MAb 2/10SN at the tumor sites. Therefore, these 2 MAbs, 2/10SN and 10/12SN, recognize MAA which appear to be unique and may prove useful for imaging purposes. PMID- 1612781 TI - Modulation of neuroblastoma cell differentiation by the extracellular matrix. AB - The effect of a complex in vitro synthesized extracellular matrix (ECM) and its components on growth and phenotypical differentiation of a human neuroblastoma (NB) cell line (HTLA230) was investigated. Rat smooth-muscle-cell (R22CIF) derived ECM composed of collagen, glycoproteins, and glycosaminoglycans (GAGs) promoted spontaneous neurite outgrowth of HTLA230 cells but did not alter their growth kinetic or cloning efficiency as compared with cells seeded onto gelatin coated dishes. The matrix significantly enhanced, quantitatively and qualitatively, the responsiveness of HTLA230 cells to retinoic acid (RA), and a substantially reduced growth rate was observed in the presence of RA with cells grown on the ECM. Biochemical modification of the composition of the R22CIF matrix by trypsin digestion and/or high-salt extraction (4 M guanidinium) demonstrated that the ratio of chondroitin sulfate to hyaluronic acid (HA) present in the ECM determines the capacity of the matrix to promote NB differentiation. A human fibroblast (T-1)-derived ECM, which has a biochemical composition of the GAG component similar to that of the trypsinized R22CIF matrix, but which has a high amount of glycoproteins, confirmed these results. Nerve-growth-factor (NGF)-induced differentiation in a variant HTLA 230 cell line was inhibited when cells were grown on an ECM with a low ratio of chondroitin sulfate/HA. The composition of the ECM thus modulates the responsiveness to various differentiation-inducing agents and alters the phenotype of NB cells. PMID- 1612782 TI - Phosphorylation and estradiol binding of estrogen receptor in hormone-dependent and hormone-independent GR mouse mammary tumors. AB - The effect of phosphorylation on the hormone-binding capacity of the estrogen receptor (ER) was investigated in hormone-dependent (HD) and hormone-independent (HI) mammary carcinomas of GR mice. Tumor cytosols were incubated with ATP under conditions previously used to study the tyrosine kinase which confers hormone binding to phosphatase-treated or in vitro-synthesized ER. The ATP-dependent increases in hormone-binding capacity of 8 out of 20 HI tumors ranged from values of 23 to 124 fmol/mg cytosol protein. The enhancement by ATP of hormone binding to ER was significantly less marked in HD and HR tumors than in HI tumors. In only 3 out of 13 HD and HR tumors was an increase ranging from 15 to 20 fmol/mg protein detected. Analysis by Scatchard plot of estradiol binding to ER showed that cytosol incubation of HI tumors with ATP markedly increased the hormone binding without any change in affinity. The data suggest that ER of HI tumors is less phosphorylated in vivo than the ER of HD/HR tumors, so that the receptor of HI tumors is more susceptible to gamma-32P-ATP phosphorylation and ATP-induced hormone binding in vitro. Western blot of ER with antiphosphotyrosine antibody showed that, in HI tumors, the large ATP-induced increase in hormone binding to ER was associated with phosphorylation on tyrosine of the receptor itself. Our findings indicate that the process of activation-inactivation of binding through tyrosine-phosphorylation/phosphotyrosine-dephosphorylation of ER observed in estrogen target tissues is altered in some HI mammary tumors. PMID- 1612783 TI - Putative invasion-specific proteins in mouse T-cell hybridomas that differ in invasive and metastatic potential. AB - Fusion of invasive, activated T-lymphocytes with non-invasive BW5147 T-lymphoma cells mainly yields highly invasive (HI), highly metastatic T-cell hybridomas. In addition, several non-invasive (NI), non-metastatic hybrids have been obtained, probably due to loss of involved gene(s) by chromosome segregation. Here we have compared a panel of HI and NI hybrids in a search for proteins specifically expressed by either cell type. MAbs were raised against HI hybrids, but out of more than 1,000 none bound exclusively to HI cells. Furthermore, polyclonal rat, rabbit and chicken antisera did not immunoprecipitate specific proteins from total lysates, and the expression of 18 (T-cell) surface markers did not correlate with invasiveness. These results indicated that the number of differences between HI and NI hybridomas was surprisingly small. This notion was confirmed by 2-dimensional gel electrophoresis. Among 1,000 detectable spots, we found only 2 clear-cut differences between HI and NI T-cell hybridomas, whereas multiple differences were found between individual hybrids. One protein (p130) was expressed at much higher levels by HI than by NI hybrids in this panel, whereas the other (p15) was only seen in NI hybrids. These proteins are primary candidates for a role in invasion. PMID- 1612785 TI - Fibroblast-dependent tumorigenicity of melanoma xenografts in athymic mice. AB - Two human melanoma cell lines, UCT-Mel 2 and UCT-Mel 3, were invariably tumorigenic in nude mice when inoculated s.c. in doses of 10(6) cells or higher; 10(5) cells or less did not give rise to tumours. In this report we show that otherwise sub-tumorigenic inocula developed into vigorously growing tumour xenografts when co-inoculated with normal fibroblasts. Fibroblasts derived from adult, neonatal or embryonic tissues all functioned as complementing cells, as did cells of human or murine origin. There was, however, a requirement for complementing cell viability, since ethanol-killed fibroblasts were inefficacious. The fibroblast effect was dose-dependent and was not observed if injections of fibroblasts and melanoma cells were separated anatomically or temporally. We have shown, by titrating admixtures of melanoma cells and fibroblasts, that fibroblasts are, in quantitative terms, more efficacious than melanoma cells as complementing cells. The system we describe provides a useful model for the study of stromal-cell regulation of tumour growth. PMID- 1612784 TI - Inhibitions by 6-hydroxydopamine and neostigmine singly or together of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats. AB - The effects of chemical sympathectomy induced by 6-hydroxydopamine (6-OHDA) and administration of the acetylcholinesterase inhibitor neostigmine, singly or together, on gastric carcinogenesis induced by N-methyl-N'-nitro-N nitrosoguanidine (MNNG), and on the tissue catecholamine concentration of the gastric wall and the labeling index of the gastric mucosa, were investigated in inbred Wistar rats. Rats received s.c. injections of neostigmine (0.075 mg/kg), and/or i.p. injections of 6-OHDA (42 mg/kg twice within 24 hr, and then 105 mg/kg every 2 weeks from 1 week later) 25 weeks after oral treatment with MNNG. Prolonged administration of 6-OHDA or neostigmine significantly reduced the incidence of gastric cancers by week 52, and in combination they had a significantly greater inhibitory effect. 6-OHDA and/or neostigmine had no influence on the histology of gastric cancers. Administration of 6-OHDA, but not neostigmine, significantly decreased the norepinephrine concentration in the antral portion of the gastric wall. The labeling index of the antral mucosa was decreased significantly by treatment with 6-OHDA or neostigmine, and decreased even more significantly by 6-OHDA plus neostigmine. Our findings indicate that 6 OHDA and neostigmine have protective effects against gastric carcinogenesis and that in combination their effects are additive. These results imply that the activities of the sympathetic and parasympathetic autonomic systems together influence gastric carcinogenesis. PMID- 1612786 TI - Arrest in late G2 or prophase of cell cycle induced by 4,4-(1,2-ethanediyl) bis (1-isobutoxycarbonyloxymethyl 2, 6-piperazinedione) (MST-16) in cultured L1210 cells. AB - The effects of MST-16, a new antitumor agent derived from bis (2, 6 dioxopiperazine), on cell growth, cell-cycle progression and DNA synthesis, alone and in combination with other antitumor agents, were investigated in murine leukemia L1210 cells in vitro. The drug showed dose-dependent inhibition of cell growth, and this effect was cell-cycle phase-specific. Flow cytometric analysis indicated that the drug could retard-arrest the cells in late G2 phase or prophase and that it did not affect the progression from G1 to G2 phase. In the presence of MST-16, the change in 3H-thymidine incorporation was proportional to the retardation-arrest of the cells, suggesting that MST-16 has no direct action on DNA synthesis itself. MST-16 could continuously retard the cells which were arrested by etoposide (VP-16); and vincristine (VCR) could block the progression of the cells arrested by MST-16, but not vice versa. The addition of MST-16 followed by VCR was more effective than simultaneous addition of the 2 drugs on inhibition of cell growth. These results will be useful in designing a reasonable regimen of MST-16 chemotherapy for malignancies. PMID- 1612787 TI - Polyethylene-glycol-modified interleukin-2 is superior to interleukin-2 in locoregional immunotherapy of established guinea-pig tumors. AB - Polyethylene glycol-modified recombinant human interleukin-2 (PEG-IL-2) represents a cytokine with prolonged circulatory half-life and increased antitumor activity as compared to recombinant interleukin-2 (rIL-2) after systemic administration. We studied whether PEG-IL-2 would also be advantageous in locoregional immunotherapy using a syngeneic tumor model. Intradermal inoculation of line-10 tumor cells into the flanks of strain-2 guinea-pigs results in a fast-growing tumor and regional lymph-node metastases. Treatment schedules were started on day 7 after inoculation in animals with established tumors. First, groups of 5-6 animals were treated with repeated intratumoral and perilymphatic rIL-2 or PEG-IL-2 injections. PEG-IL-2 caused significant growth inhibition of both the primary tumor and the regional lymph-node metastases at lower doses and with less frequent administration than rIL-2. The best schedule for PEG-IL-2 was 3 injections a week for 5 weeks, resulting in cure of 4/17 and 5/5 (p less than 0.01) animals at the 2 most efficient dose levels tested. Subsequent experiments indicated that the intratumoral and not the perilymphatic injection route was essential for the obtained antitumor effect. Furthermore, 12/12 animals cured after PEG-IL-2 treatment rejected a rechallenge with line-10 tumor cells, whereas no cures were seen after rIL-2 injections. PEG-IL-2 therefore appears to be a valuable substance for intratumoral immunotherapy. PMID- 1612788 TI - Reduced tumorigenicity of fibrosarcomas which constitutively generate IL-1 alpha either spontaneously or following IL-1 alpha gene transfer. AB - Interleukin-1 (IL-1) is a major immunoregulatory/proinflammatory cytokine which also affects fibroblast proliferation and function and therefore it was of interest to investigate whether its constitutive expression influences the in vivo tumorigenic potential of transformed fibroblastoid cell lines. Here we report on a strong correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity, using various series of oncogene-transformed NIH/3T3 derived cell lines which produce the cytokine spontaneously or upon gene transfer, following transfection with the IL-1 alpha cDNA. Reduced tumorigenicity of the constitutive IL-1 alpha producing cell lines was manifested either by inability to grow in animals or by regressions of initially growing tumors, within 2 to 3 weeks from cell inoculation. In contrast, mice inoculated with non IL-1-producing cell lines developed progressive tumors which ultimately killed the animals. Clones obtained from a non-IL-1-producing met-transformed cell line shifted from a progressive to a regressive phenotype, following transfection with an IL-1 alpha-encoding gene, inserted into an appropriate expression vector, resulting in constitutive expression of the cytokine. The effects of constitutive IL-1 expression on tumor development were observed both in histocompatible (NFS/N) and partially allogeneic (BALB/c) mice; however, they were more pronounced in the allogeneic environment. Fibrosarcomas which are non-IL-1 producers induced progressive tumors in both strains of mice at the same growth rate. The differences between the growth characteristics of the fibrosarcomas in histocompatible vs. partially allogenic mice suggest that IL-1 exerts adjuvant like effects which increase the immunogenicity of tumor-cell antigens, and they also argue against the possibility that an IL-1-mediated local non-specific inflammatory response is the major effector mechanism of tumor rejection. Indeed, in subsequent studies we shall report on the importance of specific cellular immune responses, especially cytotoxic T lymphocytes (CTLs), in the eradication of constitutive IL-1-producing fibrosarcomas. Thus, our findings may serve as the basis for novel immunotherapy strategies aimed at the induction of IL-1 expression by cells comprising the neoplasm or alternatively by local application of the cytokine in the vicinity of the tumor. PMID- 1612789 TI - Range of HPV 16 E7 antibodies in cervical cancer patients and healthy subjects. PMID- 1612790 TI - Age at menarche and obesity as risk factors for breast cancer. Evidence of an interaction? PMID- 1612791 TI - The ST segment--the herald of ischaemia, the siren of misdiagnosis, or syndrome X? AB - Syndrome X is the term applied to patients with anginal-type chest pain who, despite a positive exercise stress test, have angiographically normal coronary arteries. Such patients probably belong to a heterogeneous group, and in a proportion the exercise test is falsely positive. With the availability of more accurate techniques for the detection of myocardial ischaemia, it is apparent that some patients can be shown to develop transient myocardial ischaemia with stress. The paradox of normal coronary arteries and a positive exercise test may be resolved by improved understanding of the regulatory control of regional myocardial blood flow, particularly at the level of the microvasculature, and of the metabolic expression of myocardial ischaemia. PMID- 1612792 TI - Parathyroid hormone and genetic hypertension. AB - Recent research provides evidence that parathyroid hormone is implicated in the pathogenesis of genetic hypertension. Abnormalities in calcium metabolism in genetic hypertension have been reported. These include hypercalciuria, depressed serum ionized calcium associated with enhanced serum parathyroid hormone levels. Calcium supplement resulted in normalization of calcium metabolism and reduction in blood pressure. In addition, removal of parathyroid glands attenuated the rise in blood pressure in genetic hypertensive rat. This review focuses on the links between calcium metabolism and calcium endocrine system abnormalities and the etiology of experimental genetic hypertension. The mechanisms by which dietary supplement and parathyroidectomy lower genetic hypertension are also discussed. Although the causality of raised parathyroid hormone in genetic hypertension is not yet fully understood, we conclude that this hormone may play a permissive effect in the development of hypertension. PMID- 1612793 TI - Optimum sampling time for detection of dental bacteraemia in children. AB - A total of 458 blood cultures were taken from 229 children aged 2 to 16 yr. Each 6 ml sample was taken starting at one of the following times after the extraction of a single tooth: 10 s, 30 s, 60 s, 90 s, 120 s, 180 s, 600 s and continuously over 2.5 min. The samples were cultured in the BACTEC radiometric culture system and when positive the bacteria isolated were speciated. At 30 s 56% of the samples were positive, the highest proportion, in contrast to only 38% of positive samples at 90 s and 28% at 600 s. Over 50% of the organisms found were Viridans streptococci. PMID- 1612794 TI - Thrombolysis with tissue-type plasminogen activator following cardiac surgery in children. AB - Three children with major intracardiac or vascular thrombosis following cardiac operations were treated with intravenous recombinant tissue-type plasminogen activator. The first patient, aged 10 yr, developed a left atrial thrombus following replacement of the mitral valve with a Bjork-Shiley prosthesis. The second patient, aged 16 months, had a right atrial thrombus following a modified Fontan procedure for tricuspid atresia. Both were successfully treated with a short course of intravenous tissue plasminogen activator. The third patient, aged 19 months, developed the Budd-Chiari syndrome with occlusion of the inferior caval vein following a modified Fontan operation for double inlet left ventricle. Even though near-complete thrombolysis and recanalization of the inferior caval vein was achieved with three courses of tissue plasminogen activator on successive days, she died with failure of multiple organs. In all cases, the diagnosis was established by cross-sectional and Doppler echocardiography, and the response to therapy was monitored using the same technique. Thrombolytic therapy with systemic tissue-type plasminogen activator was safe and effective in the postoperative period, with no major haemorrhagic complications. PMID- 1612795 TI - Effects of dietary supplementation with fish oil on atherosclerosis and myocardial injury during acute coronary occlusion-reperfusion in diet-induced hypercholesterolemic rabbits. AB - We studied myocardial injury during acute coronary occlusion-reperfusion and atherosclerosis in rabbits fed a high cholesterol diet with or without fish oil supplementation. New Zealand white male rabbits were divided into 3 groups. Eight control rabbits fed with laboratory standard rabbit chow were group I. In addition to the standard chow, 15 rabbits fed with a 1% cholesterol-enriched diet for 6 weeks were group II, and 10 rabbits fed with a 1% cholesterol-enriched and 10% fish oil supplemented diet for 6 weeks were group III. Acute coronary occlusion was induced by ligating the marginal branch of the left circumflex coronary artery for 1 h, followed by reperfusion for 4 h. Myocardial injury was assessed by tissue creatine kinase activities and amino-nitrogen concentrations from the ischemic (infarct) and nonischemic (normal) myocardium, and the infarct area/risk area ratios of the left ventricle. The surface area of the atherosclerotic lesions of the aorta and pulmonary artery was measured by planimeter. There was significantly more myocardial loss of creatine kinase and amino-nitrogen in the cholesterol-fed rabbits than the controls (p less than 0.01 and 0.02, respectively). The cholesterol and fish oil-treated rabbits had a nonsignificant reduction in myocardial loss of both agents as compared to their corresponding cholesterol-fed ones. The same trend was also found in the infarct area/risk area ratio. Fish oil treated rabbits had a good effect on the reduction of atherosclerotic lesions and tissue cholesterol levels in the aorta and pulmonary artery, but not in the left ventricle.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612796 TI - Dependence of peak dP/dt and mean ejection rate on load and effect of inotropic agents on the relationship between peak dP/dt and left ventricular developed pressure--assessed in the isolated working rat heart and cardiac muscles. AB - To examine the effects of preload (mean left atrial pressure) and afterload on two so-called "contractility indices" and the effects of inotropic agents (isoproterenol and calcium) on the relationship between left ventricular developed pressure and peak dP/dt when afterload was increased, we used a modified working rat heart preparation (perfused with Krebs-Henseleit solution bubbled with a 95% O2 -5% CO2 gas mixture at 37 degrees C). The atrium was stimulated at a rate of 240/min. An increase in preload from 5 to 15 mmHg caused an increase in peak dP/dt from 1,711 +/- 293 mmHg/s to 1,971 +/- 387 mmHg/s (p less than 0.001, n = 15), and an increase in the mean systolic ejection rate from 1.28 +/- 0.31 ml/s to 2.74 +/- 0.80 ml/s (p less than 0.001). An increase in afterload (left ventricular developed pressure) from 66 to 97 mmHg produced by elevating aortic pressure caused an increase in peak dP/dt from 1,829 +/- 222 mmHg/s to 2,449 +/- 254 mmHg/s (p less than 0.001, n = 7), and a decrease in the mean systolic ejection rate from 2.12 +/- 0.36 ml/s to 1.95 +/- 0.33 ml/s (p less than 0.001). Studies using isolated rat papillary muscles ruled out the contribution of an increase in myocardial perfusion to the increase in peak dP/dt, since the maximum rate of rise in tension (dT/dt) increased with an increase in afterload during afterloaded isotonic contraction. Peak dP/dt showed a linear relationship to left ventricular developed pressure when the latter was increased by elevating the aortic reservoir and then clamping the aortic outflow tube (n = 8).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612797 TI - Acute effects of intravenous phosphodiesterase inhibition in chronic heart failure: simultaneous pre- and afterload reduction with a single agent. AB - Intravenous phosphodiesterase inhibition with milrinone is known to have a beneficial effect on haemodynamics in chronic heart failure. Its effect on lower limb capacitance vessels has not been previously investigated. We have studied the effect of intravenous milrinone in 10 patients with severe chronic heart failure. Thirty minutes after commencement of treatment mean cardiac index had risen by 26% and pulmonary artery wedge pressure, systemic vascular resistance and right atrial pressure had fallen by 51, 24 and 89%, respectively (p less than 0.05 for all changes). These changes were maintained for the 2 h observation period with no evidence of tolerance and were accompanied by a 17% increase in venous volume (p less than 0.01) and a 42% increase in ejection fraction (p less than 0.001) at 30 min; at 120 min the improvement in ejection fraction had been maintained and a further increase in venous volume to 38% above baseline was evident. The increase in venous volume was strongly correlated with the decrease in mean pulmonary artery wedge pressure and mean right atrial pressure at 30 min and 2 h (r = -0.80 and -0.69 for mean pulmonary artery wedge pressure, r = -0.88 and -0.56 for mean right atrial pressure). Milrinone therefore has clinically important venodilating properties, in addition to its known effects as an arterial vasodilator and a positive inotrope. PMID- 1612798 TI - Nonconditional logistic regression analysis of risk factors in rheumatic heart disease. AB - The prognostic risk factors in 4323 patients with rheumatic heart disease, admitted from 1970 to 1990, were analysed. The overall mortality was 31.75% in this group of patients. Single factor analysis indicated that cardiac functional classification, time of death, month of death, cardiothoracic ratio, valvular lesions, cardiogenic shock, digitalis-induced arrhythmias, intercurrent pneumonia, pleurorrhea, and hypotension were related to the overall mortality and cardiac death. Multiple factor logistic analysis indicated that for the overall mortality, the independent prognostic factors included presence of cardiac functional classification, cardiothoracic ratio and cardiogenic shock; for cardiac death, the independent factors included cardiac functional classification, cardiothoracic ratio, cardiogenic shock, digitalis-induced arrhythmias and valvular lesions. The data analysis showed that these five factors were contributory to rheumatic heart disease with synergism. PMID- 1612799 TI - How long should high-risk patients with acute anterior wall myocardial infarction be monitored? AB - In 143 patients with an acute anterior wall myocardial infarction, left ventricular ejection fraction was determined within 72 h of admission. Left ventricular ejection fraction was below 40% in 114 patients. In this group late ventricular tachycardia or ventricular fibrillation occurred in 30 patients (26%). A left ventricular ejection fraction below 40% identified all patients who developed any late ventricular tachycardia and a left ventricular ejection fraction below 30% identified all who developed late ventricular fibrillation. After discharge another 2 patients with late ventricular tachycardia were detected. Death between 48 h and 3 weeks only occurred in patients with a left ventricular ejection fraction below 30%. Thus in patients with an acute anterior wall myocardial infarction a left ventricular ejection fraction below 30% within the first 72 h after the acute event identifies a high risk for late ventricular tachycardia or ventricular fibrillation. The occurrence of late ventricular tachycardia showed a gradual increase during 3 weeks of monitoring and no cut-off point could be detected within this time-window. PMID- 1612800 TI - The management and outcome of late post-infarct ventricular tachycardia presenting to a district general hospital. AB - A review was undertaken of late post-infarct ventricular tachycardia in a district hospital cardiac care unit in order to study the clinical course of a total population of such patients from initial presentation to ultimate outcome. Thirty-six patients with this diagnosis were identified over a 3 1/2-yr period. Twelve were treated by empirically chosen antiarrhythmic drugs. Twenty-four were referred for electrophysiologically guided treatment, of whom 16 were treated by antiarrhythmic drugs, 3 by anti-ischaemic measures alone, and 5 by non pharmacological antiarrhythmic treatments (antiarrhythmic surgery, percutaneous ablation, defibrillator implantation, cardiac transplantation). Of those treated empirically, 4 died in hospital of their arrhythmia, 1 died suddenly at home, and 2 suffered non-fatal arrhythmia recurrences during mean follow-up of 20 months. There were no arrhythmic deaths in those whose treatment was guided by serial electrophysiology studies, although 4 patients died of cardiac failure or reinfarction, and 3 were hospitalised with a recurrence of ventricular tachycardia during mean follow-up of 16 months. Age, concomitant medical problems and the apparent response to initial antiarrhythmic therapy were the main factors influencing management decisions. The apparent superiority of more intensive management strategies based on electrophysiology studies must be interpreted in the context of the selection processes applied to the total population initially presenting. PMID- 1612801 TI - Clinical characteristics of acute myocardial infarction in patients with Chagas' disease. AB - From 1981 to 1988, 404 patients at our institution were found to have acute myocardial infarction. Of them, 18 (4%) had a positive fixation test for Chagas' disease. Patient age ranged from 41 to 80 years (median = 59). Eleven patients were males. Eighteen nonchagasic patients were matched by 2 year age intervals and sex with each chagasic patient. Before acute myocardial infarction, there were no differences between chagasic and nonchagasic patients with regard to the proportion of stable angina, unstable angina and coronary risk factors. Atypical chest pain occurred in 8 of 15 (53%) chagasic patients for whom this information was found in the medical records and in 1 of 18 (5%) nonchagasic patients (p = 0.003); dyspnea and palpitations occurred in 6 of 15 (40%) chagasic and 1 of 17 (5%) nonchagasic patients (p = 0.025). There were no differences between chagasic and nonchagasic patients with respect to both clinical characteristics and cardiac complications of acute myocardial infarction. Nonetheless, 4 of 11 (36%) chagasic patients for whom this information was listed in the medical records but none of 16 nonchagasic patients had normal coronary arteries (p = 0.019). Thus, chagasic patients who develop acute myocardial infarction have some peculiarities both in the clinical profile before the acute event and in the anatomy of the coronary arteries. PMID- 1612802 TI - The Hatle orifice area formula tested in normal bileaflet mechanical mitral prostheses. AB - The Hatle formula was derived empirically in native mitral stenosis and may not be valid for normal prosthetic valves. Bileaflet mechanical prostheses open fully at low flows and have minimal interindividual variation in orifice area. In these valves effective area and measured manufacturer's area should be similar. We studied 60 patients aged 58 +/- 12 yr at a mean of 5 months after implantation with a CarboMedics prosthesis. There was a coexistent aortic prosthesis in 21. All diastolic measurements were averaged over 5 beats and stroke volume was calculated from the integral of the subaortic velocity trace and the cross sectional area of the left ventricular outflow tract. For the whole group, area by the Hatle formula was 3.1 +/- 0.7 cm2 and measured area was 2.8 +/- 0.4 cm2. There was no significant correlation between these values (p = 0.329). Pressure half-time was more closely correlated with peak transmitral velocity (p = 0.012), RR interval (p = 0.015), diastolic time interval (p = 0.062) and stroke volume (p = 0.074). We conclude that the Hatle formula should not be applied to normal bileaflet mitral prostheses where pressure half-time reflects nonprosthetic factors more closely than orifice area. PMID- 1612803 TI - Choriocarcinoma presenting as intracavitary tumor in the left atrium. AB - We describe a 27-year-old woman who presented with classical symptoms and signs of left atrial myxoma. Histopathological studies of the excised tumor mass, however, revealed it to be choriocarcinoma. This is the first report of such a presentation of choriocarcinoma. PMID- 1612804 TI - Aberrant systemic artery-pulmonary venous fistula: diagnosis with Doppler imaging. AB - A 6-year-old asymptomatic girl presented with a continuous murmur at two different locations. Using Doppler imaging modalities, a small patent arterial duct and an aberrant systemic artery arising near the coeliac axis, piercing the right hemidiaphragm, and connecting to the right lower pulmonary vein were identified. Angiography confirmed the diagnosis and revealed additional pulmonary abnormalities. Doppler examination helped in planning appropriate angiographic projections and sites of the contrast medium injection. PMID- 1612805 TI - Primary leiomyosarcoma of the pulmonary trunk. AB - An unusual case of leiomyosarcoma of the pulmonary trunk in a 33-year-old woman is described. Angiography suggested a large pulmonary embolus. The patient was referred for surgery and the diagnosis was made histologically. The surgical management and postoperative course are described. PMID- 1612806 TI - Cross-sectional echocardiographic diagnosis of a congenital aneurysm of the muscular interventricular septum. AB - An 18-year-old asymptomatic male patient was detected to have a precordial systolic murmur since early childhood. A cross-sectional and Doppler echocardiographic examination revealed a congenital aneurysm of the trabecular portion of the muscular interventricular septum with a pin-hole communication with the right ventricular cavity. PMID- 1612807 TI - Endarteritis of the aortic arch in Turner's syndrome with cystic degeneration of the aorta. AB - We present a case of a 36-year-old 45 XO Turner syndrome with bicuspid aortic valve, dilatation of the ascending aorta and of the major branches of the aortic arch and multiple cysts of the aortic wall. This was complicated by endarteritis of the base of the aortic arch and production of an intraluminal structure (intra aortic debris). She also presented reactive pleural effusion and involvement of the pulmonary artery which was complicated by pulmonary embolism. Possible aetiological mechanisms are discussed. PMID- 1612808 TI - Extensive calcification of pulmonary arteries with left-to-right shunting across the arterial duct. AB - Extensive calcification of the pulmonary trunk extending to the arterial duct is described in a young adult. The unusual feature was the presence of restriction of the duct with only left-to-right shunting. The rarity of this condition and its surgical importance is emphasized. PMID- 1612809 TI - Acute myocardial infarction in two young male users of cocaine treated with thrombolytic therapy. AB - Two young men with a history of cocaine addiction were admitted to our Coronary Unit because of acute myocardial infarction, and treated with thrombolytic agents. The involved coronary artery was found to be totally occluded in both of them. We suggest that spasm may constitute one of the primary events in these patients. PMID- 1612810 TI - Pulmonary arterial aneurysms. AB - Over a period of 12 years, two cases of pulmonary arterial aneurysms were encountered in our autopsy data of 13 cases of congenital heart defects with right-sided infective endocarditis. Pulmonary arterial aneurysms are rare lesions and may be categorized as central or peripheral. Although early reports implicated tuberculosis as a major aetiologic factor, pulmonary arterial aneurysms are generally associated with congenital heart disease. PMID- 1612811 TI - Guillain-Barre syndrome following cardiopulmonary bypass. AB - Two cases of Guillain-Barre syndrome occurring after otherwise uneventful cardiac surgery using cardiopulmonary bypass are presented. Although Guillain-Barre syndrome has been reported after surgical procedures, it has never been reported after cardiopulmonary bypass. Recent literature supports an immune mediated process for Guillain-Barre. Cardiopulmonary bypass may act as the trigger for this immune mediated response. PMID- 1612812 TI - Left ventricular diastolic function with epirubicin therapy: an echodoppler study. AB - Thirty patients undergoing epirubicin therapy for primary lung cancer were studied by echocardiography and Doppler echocardiography. 2 D ejection fraction (EF) and Doppler left ventricular filling parameters (peak E, peak A, E/A ratio) were calculated before and after the completion of therapy. No differences in the mean values of these parameters were observed. However, 6 out of 30 patients (20%) showed left ventricular filling abnormalities; in 2 of them a slight reduction of EF was also noted. These abnormalities seem to be dose related. A longer term prospective study will be required to evaluate whether these findings are irreversible and to establish the clinical implications of our observations. PMID- 1612813 TI - Cyclosporine A treatment and evaluation of glomerular filtration rate in patients with a transplanted kidney. AB - According to some findings [Ross et al. 1987], the plasma concentration of creatinine (Pcr) is an inaccurate reflection of the glomerular filtration rate (GFR) in renal graft recipients with stabilized renal function, treated with cyclosporine A (CyA). In this study, we sought to determine whether the inaccuracy of GFR assessment on the basis of Pcr or creatinine clearance (Ccr) in these individuals is greater than in patients suffering from various chronic renal diseases untreated by any drugs during the examination. The study was performed in 30 renal graft recipients, treated with CyA in combination with azathioprine and prednisone. Further, 51 patients suffering from a chronic renal disease, mostly chronic glomerulonephritis or tubulointerstitial nephritis, were investigated. GFR was evaluated on the basis of polyfructosan clearance (CPF). A significant linear relation between Ccr and CPF (r = 0.829, p less than 0.001) was demonstrated in individuals with a transplanted kidney graft treated with CyA. A relationship of the same character was observed in the group of patients suffering from chronic renal diseases (r = 0.935, p less than 0.001). There is no statistically significant difference between the regression lines characterizing these relationships in both groups. A significant correlation of hyperbolic character between Pcr and CPF was found in both groups investigated (r = 0.693, p less than 0.001, and r = 0.741, p less than 0.001, respectively). The hyperbolic relationship noted in the studied groups did not differ significantly. These findings confirm a normal, or a mildly raised Pcr can be associated with a marked decrease in GFR, in some cases to a value as low as a third of the normal one.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612814 TI - Acute respiratory effects of sublingual buprenorphine: comparison with intramuscular morphine. AB - In this randomized, double-blind, placebo study, the respiratory effects of a single dose of sublingual buprenorphine (0.4 mg) were examined and compared with those induced by one dose of intramuscular morphine (10 mg) in a population of women, aged 25-65 years, admitted at the Hospital for Elective Surgery because of uterine fibromyomatosis. Some indices of control of breathing (P0.1, VT/TI, VE, VA, TI, TE, TI/TTot, RR), gas exchange parameters (D[A-a]O2, VD/VT, PAO2) and blood gases (PaO2, PaCO2) were measured in basal condition and at 30, 60, 90, 180 and 360 min after the administration of the drugs. No significant changes of the respiratory function were observed in patients who have received sublingual buprenorphine. In the morphine-group, however, mild PaO2 decrease and PaCO2 increase were found at 60 and 90 min (p less than 0.05), without any reduction of the respiratory drive activity, as shown by P0.1, VT/TI and VE. The significant FRC reduction, observed in the morphine-group (p less than 0.05), could have induced both TE shortening and RR increase with larger dead space ventilation and consequent fall of VA (p less than 0.05). These results suggest that the administration of one dose of sublingual buprenorphine (0.4 mg) does not cause any detrimental respiratory effect; on the other hand, an appreciable, although clinically trivial, worsening of the respiratory function results from intramuscular morphine (10 mg), in the absence of any obvious respiratory depression. PMID- 1612815 TI - The influence of different types of breakfast on the absorption of paracetamol among members of an ethnic group. AB - It is well known that food influences the absorption and therapeutic efficacy of many drugs. In this study, the influence of three different types of breakfast, on the absorption of paracetamol was studied in a South African ethnic population group (Tswanas). The results indicated that breakfasts with a high fat content delayed the absorption of paracetamol to the largest extent while breakfasts with a high carbohydrate content delayed the absorption of paracetamol to a lesser extent. PMID- 1612816 TI - Venous blood histamine levels and effect of terfenadine in patients with bronchial hyperreactivity. AB - Twenty-two subjects complaining of cough, chest tightness and/or shortness of breath with normal chest radiograph and normal pulmonary function test results were challenged with methacoline. Venous histamine levels were measured before and just after methacoline challenge. For comparison, a single blood sample was obtained from 10 normal subjects. Blood histamine levels were significantly higher in subjects with respiratory symptoms regardless of methacoline challenge being positive or negative (p less than 0.001). After methacoline challenge, blood histamine increased significantly in methacoline challenge positive group (p less than 0.05). Thereafter, terfenadine, a H1 antagonist, 120 mg/day were given to patients for one month. After terfenadine therapy, there was a subjective improvement of symptoms, methacoline provocation dose (PD20) increased and there was no significant change in blood histamine level. It is concluded that nonspecific challenge increases blood histamine levels and blood histamine levels seems to be a sensitive index of bronchial hyperreactivity in subjects with respiratory symptoms of unknown origin and that terfenadine is effective in the treatment of bronchial hyperreactivity. PMID- 1612817 TI - DWI/DWAI offenders and recidivism by gender in the eighties: a changing trend? AB - The study is based on a systematic random sample from the New York State's Driver License File, which contains 15,032 drivers who were convicted of DWI/DWAI at least once in the period of 1978 to 1988. The analysis reveals (1) the proportion of male offenders 20 and younger continued to decrease through the 1980s, while the proportion of female offenders 21 and older increased; and (2) the female DWI/DWAI recidivism rate began to parallel the male recidivism rate after the mid 1980s. A number of factors may be attributed to the changing DWI/DWAI structure, such as the impact of the 21 alcohol purchase age law, the change of women's roles and lifestyles, and the changing attitudes of the public and the police toward female drinking-driving. PMID- 1612818 TI - Summary of results of a comparative study of alcohol problems and solutions: Spain and Portugal. AB - This study explores through a mail questionnaire alcohol problems and solutions in Spain and Portugal including: drunk-driving, treatment services and prevention, economic issues, alcohol consumption, cultural aspects, and supply of alcoholic beverages. Consumption of alcohol in both countries is lower for men and women with college educations. Marital status has minimal effects on the consumption level of men and women in Spain and of men in Portugal. For Portuguese married women, consumption is higher. Too many bars and feasts are primary cultural adjuncts contributing to alcohol problems. PMID- 1612819 TI - Driver fatalities and DUI offenders in New Jersey. AB - Comparisons of driving and demographic characteristics were made on 407 driver fatalities (DFs) and 407 motorists convicted of driving under the influence (DUI). Significantly more DUI offenders (DOs) than DFs were men and had previous DUIs, accidents, license suspensions, and weekend "index" events. DFs with a blood or brain alcohol concentration (BAC) of 100 or above mg/dL matched most closely with DOs on negative driving events, "index" event days, and demographics. Conversely, DFs with negative BACs differed significantly with DOs on virtually all characteristics. High-BAC DFs and DOs may well be drawn from the same subpopulation of deviant drivers, whereas DFs with negative BACs seem similar to licensed drivers in general. PMID- 1612820 TI - Predictors of smoking cessation in a sample of Italian smokers. AB - In this study we identify several pretreatment characteristics which predict abstinence at 6 months. Moreover, the persistence of withdrawal discomfort and of an increased frequency of night awakenings during the first month of abstinence, together with a tendency to "slip" during Weeks II-IV, strongly predicted relapse. Our results suggest that: 1) Predictors of outcome cannot be automatically extended from one cultural context to another; 2) a careful assessment of certain variables, made while the patient is still under treatment, provides significant prognostic hints; 3) ex-smokers' sleeping and dreaming function has been ignored by the literature, whereas they may well be involved into the maintenance of the drug-free state. PMID- 1612821 TI - Smoking cessation in women: effects of the menstrual cycle. AB - Ten females in the midcycle phase of the menstrual cycle, 10 females in the premenstrual phase of the menstrual cycle, and 10 males agreed to try and stop smoking for two consecutive days. The Smoking Motivation Questionnaire and Profile of Mood States Questionnaire (POMS) were completed by all subjects beforehand. On each "no smoking" day, the POMS and a Smoking Withdrawal Questionnaire were completed. Males and midcycle females achieved significantly greater smoking reduction than premenstrual females during the "no smoking" days. Premenstrual females reported becoming significantly more tired, confused, depressed, anxious, and irritable than midcycle females. Midcycle females reported only slight changes in feeling state during cigarette withdrawal. The position of the males was broadly intermediate between the two female groups. PMID- 1612822 TI - Abstinence, reasons for not drinking, and life satisfaction. AB - This study examines the reasons given for not drinking by abstinent alcoholics with varying lengths of sobriety. A Reasons for Not Drinking Scale is tested, as well as the Purpose in Life Questionnaire and Life Satisfaction Scale. Subjects are 60 males from a VA population. Results show that subjects with less education and those treated in a detoxification setting are more likely to endorse negative reasons for not drinking. Individuals with short and long abstinence have a higher level of life "dissatisfaction" than those with moderate periods of abstinence. The study suggests that purpose in life, life satisfaction, and reasons for not drinking are important measures of progress in treatment and movement through phases of recovery. PMID- 1612823 TI - Needle-cleaning practices among intravenous drug users who share injection equipment in Baltimore, Maryland. AB - In Baltimore, Maryland, between 1988 and 1989, 2,921 intravenous drug users were recruited into a study of drug injection practices and human immunodeficiency virus (HIV) infection. Sixty-three percent reported both current use and sharing of needles; almost all these (N = 1,757) reported using injection equipment immediately after it was used by another intravenous drug user. Of the 1,757, 62% said that they "typically" cleaned the used equipment with bleach or alcohol before injecting. These data suggest that information about disinfecting needles has disseminated into this population and identifies several groups to target for interventions. PMID- 1612824 TI - Israeli Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements. AB - This article summarizes the Christian, Druze, and Moslem part of an Israeli study which was carried out in 1988 in the framework of an international comparative project conducted simultaneously also in Australia and in the USA in order to compare the perception of a set of 64 magazine alcohol advertisements by youth from three nations and various cultural and religious groups within those nations. This study is a breakthrough in the Christian, Druze, and Moslem sectors, since it is the first project in the "alcohol domain" among high school students from those sectors. The article presents the results concerning Christian, Druze, and Moslem adolescents' attitudes toward magazine alcohol advertisements. The results have implications for prevention efforts among adolescents from those three religions. PMID- 1612825 TI - Self-regulation and "addictive behavior": some theoretical remarks. PMID- 1612826 TI - Why networks? AB - The development of the network concept is prompted by the accumulated quantitative disagreement between the behaviour of single microvessels and the changes of total tissue blood flow, as well as by the ubiquitous flow heterogeneity. It is further driven by the difficulty to attach function-oriented nomenclatures to structural elements of the terminal vascular bed. So far, the efforts of mathematical network modelling have led to a reasonably coherent analysis of microcirculatory hemodynamics from available data on network geometry and blood rheology. These efforts have shown that complete data sets are important because of the non-symmetric architecture of most networks. Due to its effect on exchange efficiency, the relationship between network heterogeneity and total flow regulation remains the currently most relevant physiological problem. So far, the hypothesis of flow heterogeneity being controlled through intra network communication and consecutive readjustment of flow and flux dispersions is intriguing, but speculative. PMID- 1612827 TI - Effect of isovolemic hemodilution on microvascular perfusion in rat skeletal muscle during a low flow state. AB - The objective was to evaluate the hemodynamic effect of hemodilution during a state of experimentally reduced microvascular flow. We measured red blood cell velocity (VRBC) and density of capillaries with moving and stationary red cells (CDPER, CDSTAT) at the surface of extensor digitorum longus muscle in 26 rats anesthetized with pentobarbital. The low flow state was achieved by reducing the femoral blood pressure to 30 mmHg via a partial occlusion of the abdominal aorta. Hemodilution with a 6% PVP-40 (polyvinylpyrrolidone) solution (average hematocrit reduction from 47 to 22%) was introduced either 90 minutes before or 30 minutes after the onset of low flow state. When compared with the control state, this state was associated with significantly reduced VRBC (from 0.14 to 0.016 mm/s) and CDPER (from 32.5 to 18.7 cap/mm of test line), and significantly increased CDSTAT (from 4.5 to 13.8 cap/mm), percentage of capillaries with low VRBC, 0-0.05 mm/s, (from 35 to 94%) and VRBC heterogeneity (coefficient of variation increased from 91 to 152%). Pre-hemodilution improved microvascular perfusion dramatically during the low flow state. VRBC and CDPER increased significantly by 387 and 51%, while CDSTAT, percentage of low VRBC capillaries, and heterogeneity decreased significantly by 52, 51 and 32%. Post-hemodilution, on the other hand, showed no improvement as none of these parameters changed significantly from the low flow state. We conclude that, based on this rat model, hemodilution is more suitable as a preventive measure, rather than as a treatment, of microcirculatory disorders associated with compromised flow. PMID- 1612828 TI - Cerebral microcirculation: heterogeneity of pial arterial network controlling microcirculation of cerebral cortex. AB - Analysis of the functional behaviour of pial arterial ramifications feeding small areas of the cerebral cortex of rabbits uncovered well-defined heterogeneity of vascular responses during development of functional hyperemia. In the network of the smaller pial arteries, under 100 microns in diameter, the most active segments, the sphincters of offshoots of smaller arterial branches from larger trunks and the precortical arteries just before their penetration as the radial arteries into the cerebral cortex, have been discovered. The frequency of their dilatation was found to be higher, the latent periods of the vascular responses significantly shorter, and the degree of vasodilatation greater than of the adjacent arterial segments. An abundant amount of cholinergic nerve plexuses (containing the cholinesterase) was found in the walls of these active vascular segments, and microapplication of atropine resulted in a considerable decrease of their dilatation. These experimental results indicate the involvement of the cholinergic neurogenic mechanism in the functional vasodilatation, as distinct from the largely accepted effect of the humoral mechanism accomplished by diffusion of active vasodilatory substances from tissue elements to the walls of the feeding arterial branches. PMID- 1612829 TI - Effects of local hyperemia and edema on the biological zero in laser Doppler fluxmetry (LD). AB - The method of laser Doppler (LD) fluxmetry records the flux of moving blood cells and particles in a small tissue volume. However, also during complete arterial occlusion a flux-independent signal can be recorded, which is sometimes significantly different from the electrical zero of the instrument. This part of the signal has been called the biological zero (BZ), and can sometimes represent up to 80% of the total LD signal. In the present study, we investigated the influence of induced hyperemia produced by methylnicotinate and histamine respectively, both vasodilators but only histamine giving edema. Eleven legs of nine healthy subjects were studied. Test sites on the dorsal skin of the foot were prepared with a) histamine (10 mg/ml), b) methylnicotinate (0.1 mol/l) and c) saline. The substances were administered onto the skin with a lancet as the prick test procedure. The basal LD was measured before, and the BZ during an arterial occlusion obtained with a cuff at the ankle. Histamine induced a wheal and edema in all subjects, while methylnicotinate only caused erythema. Basal LD was significantly (p less than 0.01) increased by both substances compared to saline. The BZ was significantly higher (p less than 0.01) with histamine than with both saline and methylnicotinate. The results show that BZ is increased by vasodilation, and still more so by edema formation. It is concluded that the BZ value must always be recorded and taken into consideration when LD blood cell flux is measured in the skin. PMID- 1612830 TI - The microvascular architecture of the scalp in the human fetus at term. Implications for measuring blood gases and flow rate. AB - A microscopic study is presented on the depth distribution of the microvessels in the scalp of two human fetuses at term. The basal membrane showed a smooth line without papillary structures resulting in a thin epidermal layer of 25 microns. The distance from the scalp surface to the periosteum appeared to be almost 1.8 mm. The capillary density showed a peak of approximately 1.2 capillary cross sections per 10(4) microns 2 in the first 200 microns of the dermis. In the middle of the dermis the capillary density fell to 0.2 cross-sections per 10(4) microns 2 to rise again in the lower part of the dermis to 1.6 cross-sections per 10(4) microns 2, which remained the approximate count in the subcutaneous tissue. The arterioles and venules showed significant numbers in the lower part of the dermis and were virtually absent in the subcutis. Of all 4570 microvessel cross sections that were studied in a tissue volume of 0.6 mm3, not a single one showed the features of an arteriovenous anastomosis. The possible implications for laser Doppler flowmetry and continuous blood gas measurement of the fetal scalp are discussed. PMID- 1612831 TI - Measures to reduce the infant mortality rate in Tanzania. AB - Tanzanian health problems reflect those in other developing countries where the standard of living is low and housing and sanitation are inadequate. The major cause of infant mortality can be attributed to preventable diseases such as gastroenteritis, acute respiratory infections and malnutrition. In spite of the fact that various efforts have been made to extend primary health care coverage, particularly in rural areas, the scarcity of economic resources impedes the implementation of many health programmes. However, only by maintaining primary health care as a major part of the country's development strategy can the needs of both rural and urban people be met. PMID- 1612832 TI - Audits of nursing care in Britain: a review and a critique of approaches to validating them. AB - The literature on audits of nursing care shows a strong link between the quality of nursing care and nursing labour force issues. Early attempts to develop a universally applicable formula to set nurse staffing levels on the basis of variations in patient dependency were shown to have been based on unrealistic assumptions about the ability of scientific methods to remove the influence of judgement from such areas of decision-making. The extent to which the validity of audit instruments has been established is reviewed, showing the number of studies to be small, almost exclusively in relation to American instruments, and with inconclusive results. An extension of the concept of validity is discussed, based on House's approach [House, E.R. (1980). Evaluating with Validity. Sage Publications, London, Beverly Hills] towards establishing validity in educational evaluation. This approach explicitly acknowledges the role of judgement in the evaluative enterprise, and widens the debate about how to settle questions of validity for audits of nursing care. PMID- 1612833 TI - Curriculum innovation for gerontological nursing in Canada: a health for all systems based approach. AB - This paper presents an educational model that follows the General Systems approach and illustrates the advancement of gerontological nursing education in Canada. The model's primary focus is placed on baccalaureate education, the mandate of the nursing discipline group. The paper also touches briefly on Masters and Doctoral education. Implications for use of this model in nursing education are then linked to nursing care of the elderly. PMID- 1612834 TI - Learning from experience: nurse tutors' and student nurses' perceptions of experiential learning in nurse education: some initial findings. AB - Experiential learning and experiential learning methods have been widely described in the literature as aids to learning about nursing. This paper describes a descriptive study of nurse tutors' and student nurses' perceptions of experiential learning. Two research methods were used: in-depth semi-structured interviews of 12 nurse tutors and 12 student nurses, followed by a questionnaire survey of a total population of nurse tutors in Wales, U.K. (n = 184) and a 100% stratified sample of student nurses in Wales (n = 325). The questionnaire items were devised out of the interview data. This report offers a description of how the study was conducted and some of the findings. Notably, student nurses tended to perceive experiential learning in terms of learning in the clinical setting whilst tutors referred more to experiential learning as a classroom activity. Other findings are described and discussed. PMID- 1612835 TI - Words and actions: a study in nurse wastage. AB - This paper examines whether a group of nurses' stated intentions to leave were subsequently transformed into actual leaving actions. We argue that establishing the truth of relationships between words and actions is of fundamental importance in social science research. Nurses broadly did what they said they would do. Hence, definite intentions to leave were generally acted upon while less strong leaving intentions were not acted upon to any practically significant degree. We further investigate the link between the nurses' words and actions by reporting on a small interview study where nurses were asked why they did or did not do as they stated. The importance of these findings in terms of health authorities planning their labour force is discussed. PMID- 1612836 TI - The newly registered nurse and the cancer patient: an educational evaluation. AB - This paper reports a study which aimed to develop an understanding of newly registered nurses' attitudes, knowledge, confidence and educational needs in relation to cancer care. An educational intervention designed to meet these nurses' needs was then developed and evaluated with 127 newly registered nurses from two general hospitals. Nurses attended two different educational interventions; one group of nurses completing a 3 day experiential workshop; and a second group attended a more formal seminar programme. A third group of nurses who were unable to obtain study leave were followed up as a control group. A triangulation strategy was used to collect data from different sources, and included a baseline study, and a study of nurses before, after and 3 months following the educational interventions. Data from the study revealed the perceived need and desire for more education on cancer care, and the strong association of cancer with death amongst newly registered nurses. Significant benefits to those nurses attending the workshop were demonstrated. These differences were however less obvious at 3 months follow-up. PMID- 1612837 TI - Studies exploring self-care for the person coping with cancer treatment: a review. AB - Individuals living with an illness such as cancer and receiving chemotherapy must often meet a new set of demands, that are not amongst their usual repertoire of skills and knowledge. Little is known about how patients manage the illness of cancer and in particular what self-care actions they develop and perform to cope with the side-effects of treatment. This paper outlines Orem's theory of self care and describes its utilization in the design of a number of research studies in the cancer patient population. In particular, work which has explored the role of self-care in relationship to the control of chemotherapy induced nausea and vomiting is reviewed. The role of manipulating food and fluid intake, exercise and sleep and diversionary activities are explored; self-care is considered a vital part of the battle against combating nausea and vomiting induced by chemotherapy and further studies are urged. PMID- 1612838 TI - Improving nursing practice: the provision of equipment. AB - The quality of nursing care depends not only on the knowledge and skill of practitioners, but also on the equipment provided for their use. The availability and storage of urinary catheters was recorded in two "point prevalence" surveys in one District Health Authority. The numbers of catheters available in different locations were not related to the prevalence or "predicted incidence" of catheterized patients. The second survey documented evidence of improvements in practice, in particular a reduction in excessive and/or out-of-date stocks; a reduction in damaged stock; an increased availability of catheters with small balloons; and a greater awareness of those considerations important to a judicious choice of catheter for each individual patient. Equipment audits improve practice by raising awareness of clinical issues; by providing objective evidence of unnecessary expenditure; and by monitoring indirectly certain aspects of care such as the provision of standards and guidelines. PMID- 1612839 TI - A silent conspiracy?: some ethical issues of participant observation in nursing research. AB - In this paper I suggest that too little attention has been paid to ethical problems underlying health care research, particularly that which uses covert participant observation. Some of the chief arguments surrounding the use of deception in data collection in health care settings are evaluated, and a study by Field (1989) [Nursing the Dying. Routledge, Tavistock] in which covert observation was used is examined in relation to two moral principles--human rights and general utility. Conclusions include the responsibility of researchers to explicitly justify their approach in terms rather more than mere technical advantage, and the need to encourage the teaching and use of non-deceptive methods of data collection at this most crucial developmental stage in the evolution of nursing and health care research. PMID- 1612840 TI - The developing discipline of nursing from a Dutch perspective. AB - This article is based on a literature review and presents an overview of the development of nursing from vocation to a science based profession. It first addresses the start of formal nursing education in The Netherlands and then focuses on the developing academic discipline, which originated in the U.S.A. While the main focus is on The Netherlands, major milestones in other countries are also briefly discussed [Diepeveen-Speekenbrink (1990b), "The need for graduate nursing education and nursing research in The Netherlands: An exploratory study", a dissertation for degree of Master of Philosophy at University of Wales College of Medicine]. PMID- 1612841 TI - [Acute abdomen--differential diagnosis]. PMID- 1612842 TI - [Thrombolytic therapy]. PMID- 1612843 TI - [Fibrinolysis and thrombolytic drugs]. PMID- 1612844 TI - [Thrombolytic therapy of myocardial infarct. Status after GISSI-2 and ISIS-3]. PMID- 1612845 TI - [Thrombolytic therapy of pulmonary embolism]. PMID- 1612846 TI - [Thrombolytic therapy of deep venous thrombosis. Indications, treatment procedures]. PMID- 1612847 TI - [The status of thrombolysis in treatment of peripheral arterial occlusive diseases]. PMID- 1612848 TI - [Cerebrovascular occlusions. Indications for thrombolytic therapy]. PMID- 1612849 TI - [The value of laboratory diagnosis in thrombolytic therapy]. PMID- 1612850 TI - [New strategies and perspectives in thrombolytic therapy]. PMID- 1612851 TI - [50-year-old man with acute ischemia syndrome of both legs]. PMID- 1612852 TI - [Muscle pain, scleroderma-like skin changes and eosinophilia following administration of a psychotropic drug]. PMID- 1612853 TI - [Quo vadis--internist?]. PMID- 1612854 TI - [Two new drugs. Recombinant "human" erythropoietin (EPO: Erypo, Recormon)]. PMID- 1612855 TI - [How are auscultation phenomena (sounds) in blood pressure measurement interpreted and evaluated?]. PMID- 1612856 TI - [What is the definition of stress hypertension? Does it also present in stress test ECG?]. PMID- 1612857 TI - [Are there therapeutically relevant differences in the effectiveness and administration frequency of inhaled corticoids in bronchial asthma?]. PMID- 1612858 TI - [Therapy of cholelithiasis]. PMID- 1612859 TI - [Etiology of acute cardiovascular arrest]. PMID- 1612860 TI - [Basic measures in mechanical cardiovascular resuscitation]. PMID- 1612861 TI - [Electrical defibrillation]. PMID- 1612862 TI - [Current guidelines for cardiopulmonary resuscitation]. PMID- 1612863 TI - [Cardiopulmonary resuscitation by lay persons]. PMID- 1612864 TI - [Results of cardiopulmonary resuscitation]. PMID- 1612865 TI - [Resuscitation research]. PMID- 1612866 TI - [Increasing stress-induced dyspnea and recurrent pneumonia]. PMID- 1612868 TI - [ACE inhibitors]. PMID- 1612867 TI - [Acute atraumatic rhabdomyolysis]. PMID- 1612869 TI - [What is the current status of antihypertensive therapy in pregnancy?]. PMID- 1612872 TI - A heritage we cannot ignore. PMID- 1612871 TI - [Are the publicized advantages of thrombolytic treatment of myocardial infarct with recombinant t-PA (ACTILYSE) in comparison with streptokinase so decisive, that despite the high cost a general use of ACTILYSE is justified?]. PMID- 1612870 TI - [How should one interpret serum vitamin B12 deficiency without manifestations of pernicious anemia?]. PMID- 1612873 TI - At death's door: recollections of a medical examiner. AB - When you've been Polk County Chief Medical Examiner for nearly 20 years, you're bound to have some interesting stories to relate. Dr. Wooters recalls some of his 'stranger-than-fiction' experiences and discusses what he's learned about death investigation. PMID- 1612874 TI - Analyzing physician practice patterns. PMID- 1612875 TI - More forensic pathologists needed, says state medical examiner. PMID- 1612876 TI - Comments, speculation about February issue. PMID- 1612877 TI - Diagnosing breast cancer: progress and problems. AB - Earlier diagnosis of breast cancer has raised new questions about appropriate treatment and reconstruction. Revised guidelines for mammography are also discussed. PMID- 1612878 TI - Burying the dead. PMID- 1612879 TI - Scenarios involving confidentiality. PMID- 1612880 TI - Ensuring efficient death investigation. PMID- 1612881 TI - Triage in the ICU. AB - Some patients in intensive care units are too sick to derive much benefit from being there, while others are too well to require the technology and skills offered. When ICU resources are scarce, they may ethically be withdrawn from either sort of patient in favor of one more likely to benefit from the care. PMID- 1612882 TI - Transparency in neonatal intensive care. AB - Medical teams care for severely premature infants under conditions of emergency and uncertainty that make parental involvement very difficult. Parents can be invited into a decisional relationship with the team that enables them to assess more fully the meaning of their child's illness. PMID- 1612883 TI - The puzzle of the permanently unconscious. PMID- 1612884 TI - Whether no means no. PMID- 1612885 TI - Fetal alcohol and felony. PMID- 1612886 TI - Irrational and pregnant. PMID- 1612888 TI - Bioethics for the new Russia. PMID- 1612887 TI - Irrational and pregnant. PMID- 1612889 TI - The hidden costs of market-based health care reform. PMID- 1612890 TI - Is the biosphere a luxury? AB - Wherever did we get the idea that we are no kin to the earth's other inhabitants, and that we can therefore deal with them as we please? Several strains of thought converged to produce this way of thinking, which must now be unlearned. PMID- 1612891 TI - Medicaid recipients and psychiatric treatment. PMID- 1612892 TI - How accurate are SMR1 (Scottish Morbidity Record 1) data? AB - The accuracy of recording of data on SMR1 forms was reviewed for gastrointestinal diagnoses in the Greater Glasgow Health Board area and compared to previous studies. A total of 778 cases from 1987 formed the study sample and 761 (96.9%) were available for review. Recording on the SMR1 appears to have improved since 1971 and there were relatively few errors in the basic details. The crude agreement between DG1C data (primary diagnosis) and the casenote diagnosis was 560/761 (73.6%) with a Kappa statistic of 0.67. Agreement about the presence of arthritis (as a co-diagnosis) was poor so that uncritical use of SMR1 data might lead to serious underestimation of resource measures, such as length of stay, for patients with significant arthritis in addition to a gastrointestinal problem. In these data patients with arthritis found on casenote review and not recorded on the SMR1 had mean lengths of stay between 61% and 70% greater than patients without any evidence of significant arthritis. PMID- 1612893 TI - Who should log SHIPS? The accuracy of Scottish Hospital Morbidity Data for Wilson's disease. AB - We have studied the accuracy of the hospital diagnostic data for Wilson's disease (WD) in Scotland. The computerised records of the Scottish Hospital In-Patient Statistics provided information on 41 patients, coded as having been discharged from hospital with a diagnosis of WD. Review of the patients' case notes revealed that 12 (29.6%) did not have WD, although half of these cases had 'query Wilson's disease' on the discharge summary or letter. In the other six cases, errors arose due to miscoding by the medical records staff. PMID- 1612894 TI - Knowledge of HIV and condom use among heterosexual patients at a Glasgow genito urinary medicine clinic. AB - Knowledge of HIV and knowledge of, attitudes to and use of the condom were assessed by a survey of a sample of 778 heterosexual patients attending the genito-urinary medicine clinic at the Glasgow Royal Infirmary. The mean age was 27.4 years for men and 24.5 years for women. Over two-thirds of the men and about half of the women reported more than one sexual partner during the previous year. More than 70% reported having intercourse at least three times each week. Knowledge about HIV transmission and the condom was generally good. Over three quarters of the respondents approved of the use of the condom. However, only 27% male and 24% female respondents reported using the condom, with 11% and 8% respectively using it always. Condom use was associated with a positive attitude to the condom, having received information from the media about the condom, educational status, a belief that condoms prevented sexually transmitted diseases, and having had sex education in school. It was unrelated to age, marital status, the number of sexual partners or the frequency of sexual intercourse. The most common reported reason for not using the condom was use of another form of contraceptive. PMID- 1612895 TI - Measles, mumps, rubella antibody surveillance: pilot study in Grampian, Scotland. AB - The prevalence of measles, mumps and rubella antibodies for ages over six months was obtained using a stratified random sample of stored sera submitted in 1988 prior to the implementation of MMR vaccine. Besides reflecting the different vaccination policies for the three viruses the results showed that males display earlier sero-conversion for all three infections and a higher proportion of older males are susceptible. Two-thirds of children aged 6-15 months had antibodies to measles, the majority of which were apparently vaccine induced. However, the possibility that a few children contract natural measles before the recommended age for MMR vaccine cannot be ruled out. A system of continuous sero-surveillance to monitor the effect of MMR vaccine is suggested. PMID- 1612896 TI - Evaluation of pre-admission screening of elderly patients accepted for major joint replacement. AB - Valuable orthopaedic operating time is frequently lost because patients are found to be medically unfit for surgery on admission. One hundred and forty seven consecutive patients aged 60 years or older, who had been accepted for major joint replacement and who lived within 15 miles of the Western Infirmary, Glasgow were screened at a preadmission clinic. The screening protocol had been agreed by orthopaedic and anaesthetic staff involved in major joint replacement surgery. Some 42 patients had medical illnesses which would have resulted in surgery being postponed and a further five had their surgery cancelled. Six patients passed fit for surgery at the pre-admission screening clinic were unfit for surgery on admission. Two patients in this group had their surgery cancelled. Using the guidelines suggested, pre-admission screening could be carried out by the patient's general practitioner (GP) or by a member of the medical staff when the patient attends the orthopaedic out-patient clinic. By following a simple protocol the amount of valuable operating time lost through unrecognised or poorly controlled medical illness could be greatly reduced. Pre-admission screening should result in more efficient use of scarce hospital resources and improved patient care. PMID- 1612897 TI - The chief scientist reports.... Dissemination and implementation of research. PMID- 1612898 TI - The chief scientist reports.... Implementation of research findings. PMID- 1612899 TI - The 1990 contract: have patients noticed? AB - We carried out a questionnaire survey in a Semi-urban General Practice in Renfrewshire to evaluate patients' knowledge and understanding of changes to General Practitioner services six months after implementation of 'The 1990 Contract'. The survey assessed the point prevalence of patients' knowledge in an opportunity sample. A total of 237 patients attending morning surgery during one week in September 1990 were asked to complete a short questionnaire. Despite 38% of respondents declaring they were aware of the changes, only 10% of the respondents showed evidence of understanding of the changes. There was a lack of perceived usefulness of Well Person Checks despite a relatively good understanding of what this involves. Most of the recent changes in General Practice were perceived as being useful or extremely useful to patients after they had been explained. It is suggested that further publicity with careful targeting and explanation is required before the public can make appropriate and effective use of these changes. PMID- 1612900 TI - From dissemination to use: management and organisational barriers to the application of health services research findings. PMID- 1612901 TI - Information and medical audit: a 'bottom up' approach. PMID- 1612902 TI - Conference on thrombolytic therapy in the early treatment of acute myocardial infarction. Glasgow, June 14, 1991. PMID- 1612903 TI - [Multiple primary malignant tumors in patients with malignant melanoma of the skin]. AB - The incidence of further malignant tumors was analyzed by means of a retrospective study in 2335 melanoma patients. During the follow up 85 patients (3.64%) developed a second malignant tumor: 29 patients multiple primary malignant melanomas (mm), 49 a mm and a further nonmelanocytic malignant tumor, and 7 multiple primary mm and an additional non-melanocytic malignant tumor. Statistical calculations revealed that female melanoma patients have a 20 fold, and male melanoma patients a 30 fold increased risk to develop further malignant melanomas. In contrast, there was no increased incidence of non-melanocytic malignant tumors, breast carcinoma included. A total skin examination has therefore to be performed during follow up investigations of melanoma patients for early detection of further malignant melanomas. PMID- 1612904 TI - [Intralesional therapy of melanoma metastases with recombinant interferon-beta]. AB - In ten patients with metastasizing melanomas, discontinuous intratumoral treatment with recombinant interferon beta (rIFN-beta) was administered into 19 cutaneous or palpable subcutaneous metastases. Among the 16 metastases treated with 5 x 10(6) IU per injection, 8 showed partial or complete remission. No recurrence was observed during the 4-9-month follow-up period. There was no regression in 3 metastases treated with 3 x 10(6) IU rINF-beta per injection. No systemic antineoplastic effects were observed in any of the cases. The IFN-beta serum levels were measurably increased following intratumoral application. Local treatment led to a significant increase in (2'-5')oligoadenylate synthetase in the mononuclear blood cells and in the serum. Side-effects of the treatment were moderate; there was a temporary increase in transaminases, a decrease in thrombocytes and influenza-like symptoms. The results show that IFN-beta has a dose-dependent antitumour effect on malignant melanomas. PMID- 1612905 TI - De Sanctis-Caccione syndrome: xeroderma pigmentosum with oligophrenia, short stature and neurologic disorders. AB - A 6 year-old boy with de Sanctis-Cacchione syndrome is reported. This syndrome is characterized by the triad xeroderma pigmentosum (XP), mental deficiency and neurological disturbances. The patient's cells were assigned to genetic complementation group A by use of the cell fusion technique. DNA repair capacity as measured by unscheduled DNA synthesis (UDS) was drastically reduced to 7.5%, compared with 100% of the controls. The rate of sister chromatid exchange (SCE), an indicator of the hypermutability in XP, was clearly elevated after ultraviolet radiation of skin fibroblasts of the patient. PMID- 1612906 TI - [Two superficially spreading malignant melanomas on nevus spilus]. AB - A case of a 49-year-old patient with two superficial spreading melanomas arising from a naevus spilus is presented. Although opinions differ on the potential for malignant transformation in naevi spili, they should be carefully watched, and if changes are found these lesions should be subjected to histopathologic examination. PMID- 1612907 TI - [Benign symmetric lipomatosis]. AB - Benign symmetric lipomatosis is a rare disease that predominantly affects males. A close correlation with alcohol and nicotine abuse, metabolic disturbances and malignant tumours of the upper airways has been observed. We report the case of a 61-year-old female patient whose first clinical lesions had appeared more than 30 years earlier. The huge enlargement of fatty tissue had also involved her face. Case history, laboratory findings and radiological and ultrasound examinations allowed us to exclude metabolic disturbances and associated diseases. PMID- 1612908 TI - [Stewart-Bluefarb syndrome]. AB - We describe a 17-year-old Turkish girl with painful ulcerative pseudo-Kaposi lesions on the left foot and partial giant growth of the same leg. Stewart Bluefarb syndrome is discussed with reference to this case. PMID- 1612909 TI - [Sensitization by cutaneous and epicutaneous tests]. PMID- 1612910 TI - [Telangiectasis after varicose vein exeresis]. PMID- 1612911 TI - [Early detection for prevention of malignant melanoma in Berlin]. PMID- 1612912 TI - [Comment on the short report by H. Krause and E.-I. Grussendorf: Syntopy of Bowen disease and mustard gas scar]. PMID- 1612913 TI - [The sun and malignant melanoma]. AB - The aetiological role of sunlight in the development of cutaneous malignat melanoma (CMM) is still controversial. The aim of the present review is to discuss the contradictory findings and to reinterpret them in the light of recent epidemiological results. The following clinical and epidemiological features have raised doubts on an aetiological impact of sunlight in CMM development: the anatomical distribution of CMM does not closely match the body areas most exposed to sunlight, and CMM is most common during the middle decades of life (except for the subtype of lentigo maligna melanoma, which accounts for 10% of all CMM). Furthermore, no elevated CMM risk after sunburns or increased sun exposure has been detected in most of the case control studies performed so far. The most important risk factors, however, were the total number of melanocytic naevi in whole-body counts followed by such pigmentation characteristics as skin type and hair colour. On the other hand, the CMM incidence increases in white populations with increasing proximity of domicile to the equator and thus with increasing intensity of UV irradiation, and 5-10 times higher incidence rates have been reported from Australia and the southern states of the USA than from Europe. In industrialized nations with white populations a steep increase in CMM incidence has been described, with the main rise in body regions more frequently exposed to the sun in the last decades (trunk in men and boys and lower extremities in girls and women). Two results from recent epidemiological studies may help to clarify the contradictory findings above: first, sunburn in childhood and adolescence was shown in several case control studies to significantly elevate the risk of melanoma development, but further sunburn during adulthood did not contribute to any further risk elevation. Secondly, a study in Canadian school children revealed significantly higher naevus counts in subjects with numerous or severe episodes of sunburn in the previous 5 years. In conclusion, exposure to the sun in childhood and adolescence induces melanocytic naevi, which are known as markers of an elevated melanoma risk as well as possible precursors of CMM. Strategies to reduce melanoma incidence should therefore begin by restricting exposure to sunlight in young children and adolescents. PMID- 1612914 TI - [New perspectives in hair research: in search of the "biological clock" of the hair cycle]. AB - The hair follicle is not only a clinically and commercially important tissue, but can also serve as a fascinating model for studying epithelial-mesenchymal neuroectodermal interactions. Recently, this has led to a renaissance of hair research, which this speculative review attempts to outline. The unanswered key questions in hair biology are defined before we focus on the crucial search for the "biological clock" that governs the hair cycle. Specifically, we delineate the clinical importance of understanding the mechanisms of catagen induction and propose an immunological mechanism of catagen induction. New research trends are discussed against the background of their potential significance for improving the still frustrating management of hair diseases. PMID- 1612915 TI - [The clinical spectrum of organ manifestations of tuberous sclerosis]. AB - Since the first description of the classic triad of adenoma sebaceum, epilepsy and mental retardation by Vogt, various manifestations have been added to the clinical picture of Bourneville-Pringle disease or tuberous sclerosis. Diagnosis, therapy and potential complications of the more frequent manifestations are summarized. Since even oligosymptomatic patients may develop dangerous complications, the importance of thorough examination is emphasized. PMID- 1612916 TI - [Actinic prurigo]. AB - Actinic prurigo is a rare idiopathic photodermatosis, which shares some features with atopic dermatitis, polymorphous light eruption, hydroa vacciniforme and persistent light reaction. It is, however, recognized as a distinct entity. Among American Indians a familial variant is observed. Characteristic features are a chronic course with sustained exacerbations, which are seasonal at first, but later perennial. The disorder may improve in adulthood. The typical clinical features are urticarial plaques a few hours after UV exposure, and a persistent eczematous, prurigo-like rash distributed over skin areas exposed to light but sometimes extending even into photoprotected areas. Therapy is extremely difficult and unrewarding. In the present paper the entity is defined and three typical cases are presented. PMID- 1612917 TI - [Dermatoglyphic diagnosis in patients with atopic eczema]. AB - The purpose of this investigation was to find out whether the new Dermalog system could be used in conjunction with dermatoglyphics in patients with atopic dermatitis. For this purpose, 92 patients with atopic eczema (58 women and 34 men) were examined and were compared with two different control groups. The first control group, representing the normal population, consisted of 100 female and 100 male randomly selected subjects. The second control group (55 women and 24 men) excluded any persons with a history of atopic syndrome. First of all, hand and fingerprints were taken. The data were stored in a computer and were statistically analysed with the aid of significance and discrimination tests. Evaluation of the patients' data showed no significant difference from the first control group. Results in the second, selected, control group were better. For example, in this group, in which the probability was 93.1%, 76.4% of the women examined were found to have atopic dermatitis. The probability among the male patients examined was 99.9% and the corresponding sensitivity, 77.0%. PMID- 1612918 TI - [Epidemiology and prognosis of subungual melanoma]. AB - Among a total of 2038 cases of malignant melanoma, 42 tumours (approximately 2%) were located sub- and periungually. The matrices of thumbs and halluces were primarily affected. Girls and women were more frequently affected than boys and men, and a broad "pyramid of age" was obvious. The mean age for both sexes was 61 years. A mean of 1.5-2 years elapsed between the appearance of the first symptoms and establishment of a definitive diagnosis. Pigmented tumours were recognized earlier than non-pigmented ones. The prognosis in melanoma of the nail has usually been found to be poor. The curves for both survival and recurrences display an initial steep downward course. A flatter course is noted for the survival curve beyond 24 months postoperatively and for the survival curve beyond 48 months after surgery. The 5-year disease-free survival rate following operative removal of the tumour or amputation of the digit is 0.50% for subungual melanoma of the hand and 0.31% for subungual melanoma of the foot. By 10 years after operative removal of the tumour, 43% of the patients with subungual melanoma of the feet are still free of disease. Similar differences are found in the length of survival. The 5-year survival rate is 0.57 for subungual melanoma of the hand and 0.48 for melanoma of the foot. The 10-year survival rates, however, are 0.41 and 0.22, respectively. Significant differences between hand and foot cannot be verified in the rate of subungual melanoma. PMID- 1612919 TI - ["Pseudothrombosis" of the lower leg, induced by a ruptured Baker's cyst]. AB - A sudden onset of unilateral swelling and tenderness on pressure of the calf with no history of trauma is suggestive of vein thrombosis. Baker cysts, especially if ruptured, mimic the clinical picture of deep vein leg thrombosis. The examination method of choice is duplex sonography. We report on a 30-year-old man who was admitted to our hospital with signs of deep vein leg thrombosis. Phlebography revealed normal venous circulation. Examination by duplex sonography showed a ruptured Baker cyst. No intra-articular lesions of the knee joint were revealed by arthroscopy. Histological examination of the biopsy specimens of the synovia showed no specific pathologic condition. The clinical signs improved with conservative treatment. PMID- 1612921 TI - [CO2 laser treatment of rhinophyma]. PMID- 1612920 TI - [Endemic dermatophytes in Switzerland: a simple method of identification]. PMID- 1612922 TI - [73d Annual Meeting of the Swiss Society of Dermatology and Venereology 27 and 28 September 1991 in Geneva]. PMID- 1612923 TI - [Nailfold capillaroscopy in dermatology]. PMID- 1612924 TI - [Comment on the contribution by Z. Battyani, M. Magyarlaki, E. Zombai and I. Schneider: Disseminated cicatricial pemphigoid]. PMID- 1612925 TI - Multilocus DNA fingerprints in gallinaceous birds: general approach and problems. AB - Multilocus profiles were investigated in five different species of Galliformes (ring-necked pheasant Phasianus colchicus, Indian peafowl Pavo cristatus, Japanese quail Coturnix coturnix japonica, domestic chicken Gallus gallus, and red grouse Lagopus lagopus scoticus) using two human multilocus probes (33.6 and 33.15) in combination with each of four restriction enzymes (AluI, DdeI, HaeIII or HinfI). All the species show a DNA fingerprint-like pattern using at least one restriction enzyme in combination with each multilocus probe. The number of bands detected and the value of the index of similarity for each species differ significantly between the profiles obtained with each multilocus probe. Some enzyme/probe combinations reveal strong cross-hybridization of the multilocus probes with satellite or satellite-like DNA sequences in pheasant, peacock, quail and chicken, which partially or completely prevented scoring of the profile. The choice of restriction enzyme was found to influence the number of bands, the value of the index of similarity and the probability of obtaining an identical fingerprint between unrelated individuals. The Mendelian inheritance and independent segregation of the fragments detected using AluI was investigated in three species (ring-necked pheasant, Indian peafowl and red grouse). Some bands were shown to be tightly linked. An extreme case was encountered in the red grouse, where 12 of the 15 bands scored in one parent represented only two, apparently allelic, haplotypes and so derived from a single locus. However, fingerprint patterns will often be adequate for use in paternity analyses, such as in behavioural studies, despite the occurrence of haplotypic sets of bands. Identical DNA multilocus profiles were sometimes observed between captive-bred siblings in one species. These results emphasize the desirability of determining, in each new species, the optimal experimental conditions as a preliminary to any behavioural or population genetic studies that use the multilocus DNA fingerprinting methodology. PMID- 1612926 TI - Remating effects on the genetic structure of female life histories in populations of Drosophila mojavensis. AB - A quantitative genetic analysis of nine adult fitness components was performed in two populations of cactophilic Drosophila mojavensis under natural conditions of fermenting cactus and ethanol vapour. Female progeny from 18 sires and 36 dams were treated to a range of six exposure periods to males to assess effects of remating frequency on female fitness. Lifetime fecundity increased with increasing male exposure, but longevity showed an intermediate optimum with temporary exposure to males of 2-4 days. Narrow-sense heritabilities were significant for egg production traits while broad-sense heritabilities were significant for longevity-related traits. Positive genetic correlations between components of fitness were expressed among functionally related traits, e.g. longevity was positively correlated with lifetime fecundity, the number of clutches laid, clutch size, and the number of eggs laid per day. Negative genetic correlations were detected between early and late life fecundity suggesting genetic tradeoffs among components of adult fitness. PMID- 1612927 TI - Evolution of reproductive systems in filamentous ascomycetes. II. Evolution of hermaphroditism and other reproductive strategies. AB - The evolution of different reproductive systems in filamentous ascomycetes is studied in a population genetic model. These fungi differ essentially from higher plants and animals because mating types can exist in addition to male and female gametes, and the conidia serve as both male gametes and asexual spores; moreover, selfing is genetically equivalent to asexual reproduction in these haploid organisms. A variable fitness of ascospore production is predicted as the explanation for the evolution of two systems that abundantly exist in nature: hermaphroditism in heterothallic species and the formation of both asexual and sexual spores in homothallic species. Imperfect fungi will evolve if sexual spores do not show a remarkably higher fitness than asexual spores. PMID- 1612928 TI - The evolutionary history of Drosophila buzzatii. XXIV. Second chromosome inversions have different average effects on thorax length. AB - We demonstrate a genetic correlation between rearrangements of the second chromosome of D. buzzatii and thorax length, as a measure of body size. The results indicate that 2j and 2jz3 arrangements are correlated with large size, whereas 2st arrangement is correlated with small size. Some inversions (2st and 2jz3) show dominant effects and others (2j/jz3) exhibit overdominance. These results show that at least 25 per cent of body size variation may be accounted for by the studied karyotypes. The possible integration of the genotypic, phenotypic and fitness levels, and also the possible implications to life-history evolution theories, are discussed. These results suggest that, under moderate to high heritability values, some kinds of chromosomal endocyclic and/or balancing selection may be valuable mechanisms for maintenance of body size variation. PMID- 1612929 TI - [Effect of inhaled environmental pollutants on the mucous membrane of the upper airways]. AB - Diseases of the mucosa of the upper respiratory tract have increased in the last few decades. In epidemiological studies, an increase in the rate of allergies has especially been noticed. The offensive particles from the environment meet human organism in the respiratory mucosa of the nose: the function of the mucosa depends partly on the protective function of the mucus, ciliae and swelling bodies of the mucosa and partly on the abundant number of immunocompetent effector cells in the subepithelial lamina propria. Of central interest are the mast cells, which initiate reactions by means of the exocytosis of mediators: the hyperergic, anaphylactic reaction and the hyper-reflectoric, anaphylactoid reaction. Environmental noxious agents (sulfur dioxide, nitrous oxides, ozone, carbohydrides and dust particles) influence in different ways the pathological reactions of the mucosa: they provoke inflammatory reactions through toxic and chemical-irritative effects. They lead to the initiation and perpetuation of allergies. This happens through the changing spectrum of allergen exposition, through direct changing of the surface and structure of proteins of the allergens and through the strengthening of the humoral and cellular mechanisms, which are part of the initiation and perpetuation of allergies. Environmental noxious agents initiate hyper-reflectoric reactions of the mucosa, which seems to be the most impressive factor causing the change in rhinological diseases nowadays. Environmental noxious agents are partially responsible for the "priming effects." PMID- 1612930 TI - [Functional endoscopic ethmoid bone revision in inflammatory paranasal sinus diseases in childhood]. AB - A total of 57 children aged between 5 and 15 years underwent endoscopic ethmoid surgery for recurrent acute or chronic rhinogenic sinusitis, chronic sinusitis associated with bronchial asthma or chronic bronchitis, early rhinogenous orbital complications and paranasal sinus disease associated with mucoviscidosis. The indications for surgical intervention are based on symptoms, the findings on nasal endoscopy and a CT scan of the paranasal sinuses in the coronal plane. The preoperative examination shows that in childhood there are endoscopically detectable anatomical variations of the ethmoid bone (pneumatised middle nasal concha, reversed curvature of the middle turbinate and contact between the uncinate process and the turbinate) that create the conditions for the development of inflammatory paranasal sinus diseases. Careful elimination of these obstructions can accomplish complete cure of the inflammation, and early orbital complications can be treated effectively by combination of surgery with infusion of antibiotics. All surgery was performed under endotracheal anaesthesia using the endoscopic technique described by Messerklinger. The follow-up period was between 6 and 18 months. With the exception of children suffering from mucoviscidosis, cure of the paranasal sinus disease and rhinomanometrically demonstrable improvement of the nasal breathing was achieved in all cases. On the basis of our results a conservative endoscopic approach is recommended as an effective surgical method for the treatment of paranasal sinus disease in childhood. PMID- 1612933 TI - [Preoperative vestibular diagnosis in therapy of Meniere's disease]. AB - Surgical treatment of Meniere's disease is indicated in patients with severe attacks who have failed drug therapy. A decision between a conservative or destructive procedure demands firstly exclusion of patients with non-otogenic diseases, bilateral disease or complete unilateral loss of function, and secondly assessment of the laterality of the disease, of residual labyrinthic function and of vestibular compensation. A total of 185 patients with Meniere's disease were investigated. All of them had a history and clinical signs that indicated surgery. Canal function, otolith responses and vestibular compensation were examined, in addition to routine preoperative tests as recommended by the Committee on Hearing and Equilibrium of the American Academy of Ophthalmology and Otolaryngology. Of the 185 patients 22% had findings that contraindicated surgery, 4% suffered from Meniere's disease in the opposite ear, 6% showed no signs of vestibular compensation and 12% had dead labyrinths on the side of the cochlear disease. No caloric response was elicited from the labyrinth by thermal bilateral testing in 25% of the 185 patients. In patients who were thought to have dead labyrinths based on routine caloric tests, residual canal function was detected by means of 20 degrees C stimulation in the prone and supine position. Without extensive vestibular testing the indications for surgical treatment of Meniere's disease will be incorrect in 47% of patients. PMID- 1612931 TI - [Late results of endonasal ethmoid bone operation with special reference to polypous sinusitis]. AB - Out of total of 164 patients with chronic sinusitis undergoing intranasal microsurgery, 94 patients were submitted to a detailed analysis one year later. The patients were divided into groups of polypoid and hyperplastic sinusitis, depending on the morphological appearances and the histology of the tissue removed. Patients with polyps showed a significantly higher rate of recurrent (47%) than patients with hyperplastic sinusitis (8.6%). Allergy or bronchial asthma did not influence significantly the rate of recurrence in patients with nasal polyposis, whereas patients with a hyperplastic sinusitis showed a higher recurrence rate if they were atopic as well. However, even patients with polypoid sinusitis gained marked long-term relief of nasal obstruction and other symptoms. PMID- 1612932 TI - [Complications of endonasal micro-endoscopic ethmoid bone operation]. AB - We examined the frequency and site of major complications after intranasal micro endoscopic ethmoidectomy. Injury of the orbital periostium was significantly more frequent on the right than on the left side, but there was no side predominance for damage to the dura mater. Surgery on the lamina papyracea and the lateral wall of the sphenoid sinus is more dangerous on the side on which the surgeon stands during the operation. The use of the microscope, the endoscope and preoperative CT scan of the paranasal sinuses helps to avoid major complications. PMID- 1612934 TI - [Ultrasonic diagnostics of the external nose]. AB - Twenty megahertz ultrasound B-scanners achieve an axial resolution of 80 microns. The range of 7 mm in soft tissue suffices for imaging of dermal and cartilaginous structures with anatomical precision, and the form, position and diameter of the cartilaginous structures of the nose can be assessed. Distinct echoes within the cartilage indicate inflammation or trauma. The position, scarring and rate of resorption of implants can be observed non-invasively. PMID- 1612936 TI - Testing osteopathic medical concepts in a real-life setting. PMID- 1612935 TI - [Intraoperative monitoring of early auditory evoked potentials in hearing acoustic neuroma patients complemented by cochlear nerve action potentials]. AB - Hearing preservation was attempted in eight cases of acoustic neurinomas with good preoperative hearing. This was successful in 3 cases. Brain-stem auditory evoked potentials (BAEP0 were monitored in all cases, and compound nerve action potentials (CNAP) were recorded from the cochlear nerve in the last 3 cases. The BAEP was extremely sensitive to intraoperative manipulation. Intraoperative loss of wave V in BAEP was observed not only in all 5 cases with postoperative hearing loss, but also in 2 out of 3 cases with successful hearing preservation. CNAP correlated better with the hearing outcome than BAEP. In the cases where hearing was preserved, intact CNAP responses were demonstrated at the end of the operation. Conversely, deterioration of CNAP was seen in a case of postoperative hearing loss. CNAP was 10-15 times larger in amplitude than BAEP, so that the new responses were obtainable in shorter intervals. This capability of frequent examination seemed to increase the possibility of avoiding irreversible damage to the hearing by changing surgical tactics. The addition of CNAP monitoring is a good supplement to conventional BAEP monitoring in acoustic neurinoma surgery. PMID- 1612937 TI - Patient involvement key to enhancing doctor-patient relationship. PMID- 1612938 TI - HIV clinical training enhances DOs skills in the fight against AIDS. PMID- 1612939 TI - 'Mouse elbow': a new repetitive stress injury. PMID- 1612940 TI - Variety of vena caval filters improves treatment options for pulmonary embolism. PMID- 1612942 TI - Suggestions for diagnosing avascular necrosis of the hip in the 1990s. AB - Avascular necrosis of the hip is a serious clinical problem encountered by primary care physicians. It requires early detection for proper management and treatment. The clinician should be aware of the imaging modalities available for evaluation of patients with suspected avascular necrosis. Traditional studies include plain-film radiography, computed tomography, and planar bone scintigraphy. Magnetic resonance imaging and single-photon emission computed tomography bone scanning have been developed to such an extent that they are now the most sensitive indicators of early avascular necrosis. The authors review currently available imaging modalities and provide a practical approach to the assessment of patients with suspected avascular necrosis of the hip. PMID- 1612941 TI - Lyme disease. AB - Lyme disease, a multisystem disorder, has now been reported to the Centers for Disease Control from 43 states of the United States. The disease is a tick transmitted infectious disorder caused by the spirochete bacterium Borrelia burgdorferi. Lyme disease typically begins with the symptoms of flu associated with a characteristic skin rash, erythema chronicum migrans. The diagnosis of Lyme disease is best made by clinical examination and epidemiologic history, with serologic studies supporting the clinical diagnosis. Prompt diagnosis and early treatment with antibiotics will often lead to the resolution of symptoms and the prevention of late complications, Lyme carditis, neurologic manifestations, and arthritis. PMID- 1612943 TI - DNA technology. AB - Scientific developments in molecular biology enable clinical laboratory testing to directly examine genetic information coded in biologic specimens. These efforts, accomplished by the use of DNA probe technology in the in situ hybridization and other tests will allow for the specific identification of pathogens; recognition of genetic diseases; and the critical evaluation of the genetic basis of cancer. The authors discuss the concepts and uses of DNA testing. PMID- 1612944 TI - Counseling the patient with newly diagnosed HIV infection. AB - This monthly series was developed from the AOA Task Force on AIDS Writers' Workshop, held August 16 to 18, 1991, in New York. The workshop was sponsored by an education grant from Burroughs Wellcome. It will provide brief clinical updates and perspectives on the human immunodeficiency virus (HIV). Readers may request tear sheets from the AOA editorial offices. PMID- 1612945 TI - Guidelines for designing resident rating forms. AB - A well-designed rating form provides one means to evaluate a resident's clinical performance. A clear perception of the program's goals is the foundation on which an original--or revised--design should rest. Suggestions for three different types of rating forms are presented here. PMID- 1612946 TI - Sarcoidosis masquerading as eosinophilic pneumonia. AB - A 29-year-old woman presented with progressive dyspnea, fever, cough, and weight loss. A chest roentgenogram revealed bilateral peripheral infiltrates suggestive of chronic eosinophilic pneumonia. Bronchoscopic evaluation, as well as a therapeutic trial of corticosteroids, was nondiagnostic. Open lung biopsy revealed findings consistent with a diagnosis of sarcoidosis. Roentgenographically, differentiating between sarcoidosis and chronic eosinophilic pneumonia can be difficult. A diagnostic approach, as well as the differential diagnosis of bilateral peripheral pulmonary infiltrates, is discussed. PMID- 1612947 TI - Choriocarcinoma of the kidney. AB - Choriocarcinoma is a malignant germ cell tumor that usually arises from a previous gestation, but may also arise from germ cells anywhere along their known migratory pathway during fetal development. Gestational choriocarcinoma is highly sensitive to chemotherapy. This malignancy is known to undergo spontaneous regression of the primary tumor, which, in the face of metastases, may obscure the primary tumor site. The authors report the case of a patient with choriocarcinoma who was seen with pulmonary metastases and a single large lesion in the kidney 5 years posthysterectomy. The problems in resolving the primary site and the importance of a tissue diagnosis before nephrectomy are discussed. PMID- 1612948 TI - Induction chemotherapy in advanced head and neck tumors: results of two randomized trials. AB - From March 1983 to December 1989, 208 patients with locally advanced squamous cell carcinoma of the head and neck were successively included into two randomized induction chemotherapy trials. The chemotherapy regimen of the first trial, which included 100 patients, consisted of two cycles of a combination of cisplatin, bleomycin, vindesine and mitomycin C; while that of the second trial, which included 108 patients, consisted of three cycles of a combination cisplatin, 5-fluorouracil by continuous infusion and vindesine. Local treatment was the same in the two trials: primary radiotherapy in all patients. The response was then evaluated; in the case of a poor response at 55 Grays surgery was performed; otherwise, radiotherapy was continued to full doses (possibly followed by salvage surgery). The tumor and lymph node responses to chemotherapy (complete and partial response) were higher in the second trial than in the first: 70% versus 50% for primary lesions, 47% versus 25% for lymph nodes. The toxicity of the two chemotherapy regimens was minimal. In the two trials, an initial major response to chemotherapy predicted subsequent efficacy of irradiation in 80% of the patients. The significance of the complete response at the end of the irradiation varies with the previous response to the chemotherapy. With a median follow-up of 60 months with the first chemotherapy regimen and 30 months with the second, overall survival and disease-free interval were very similar in the two groups. The incidence of distant metastasis was significantly reduced (p less than 0.03) with chemotherapy. This trial suggests the need to test new chemotherapy protocols according to new schemes of treatment, with chemotherapy given concurrently with or following the completion of standard treatment by means of multicenter randomized trials. PMID- 1612949 TI - Bulky endocervical carcinoma: a 23-year experience. AB - Between 1962 and 1985, 371 patients had initial treatment for bulky endocervical carcinomas of the uterine cervix at The University of Texas M.D. Anderson Cancer Center. All patients had concentric expansion of the cervix by tumors that measured at least 6 cm in greatest transverse diameter. Of the 361 patients treated with curative intent, 211 (57%) had FIGO Stage I disease that was believed to be confined to the uterus, 59 (16%) had FIGO Stage IIA disease, and 101 patients (27%) had FIGO Stage IIB disease. Median follow-up time of surviving patients was 130 months. Actuarial survival rates of 361 patients treated with curative intent were 54% and 48% at 5 and 10 years, respectively. The actuarial pelvic disease control rate was 76% at 10 years. Patients whose tumors were less than 8 cm in maximum diameter (279 patients) had a better survival rate than those with tumors greater than or equal to 8 cm in diameter (92 patients) (p less than 0.01). Of the 282 patients who underwent lymphangiography, survival rate was significantly better for those with negative studies than it was for the 113 patients (40%) with positive or suspicious studies (p less than 0.01). There was no correlation between FIGO stage and survival rate (p = 0.64) or pelvic control rate (p = 0.59). Of patients treated with curative intent, treatment was by radiation alone (RT) in 244 (68%) or by radiation followed by hysterectomy (RT+S) in 117 (32%). Although there has been an overall shift in policy away from the use of adjuvant hysterectomy during the past decade, many patient selection factors also influenced the choice of treatment during the study years, resulting in a significantly higher proportion of patients with adverse prognostic features in the RT group. Patients chosen for treatment with RT alone had a greater likelihood of having tumors greater than or equal to 8 cm (p = 0.03), FIGO stage IIB (p less than 0.01), positive lymphangiogram (p = 0.02), and persistent palpable parametrial disease after external radiotherapy (p less than 0.01). Patients treated with RT alone also had a lower overall survival rate at 10 years than patients treated with RT+S (45% vs 64%, p less than 0.01). Although multivariate analysis suggested that treatment had an independent influence upon survival rate, it was difficult to draw firm conclusions about the value of adjuvant surgery because of the numerous biases in patient selection, some of which may have been difficult to quantify.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1612950 TI - Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. AB - Forty-three patients were treated with extended field irradiation for periaortic metastasis from carcinoma of the uterine cervix (FIGO stages IB-IV). Twelve patients (28%) remained continuously free of disease to the time of analysis or death from intercurrent disease, 20 (46%) had persistent cancer within the pelvis, 11 (26%) had persistent periaortic disease, and 23 (53%) developed distant metastasis. The actuarial 5-year survival rate was 32%. The results correlated well with the periaortic tumor burden at the time of irradiation. None of 19 patients (0%) with microscopic or small (less than 2 cm) periaortic disease had periaortic failures, compared to 29% (4/14) of those with moderate-sized (2-5 cm) disease and 70% (7/10) of those with massive (greater than 5 cm) periaortic metastasis. Similarly, the 5-year survival rates were 50% (6/12) with microscopic disease, 33% (2/6) with small gross disease, 23% (3/13) with moderate-sized disease, and 0% (0/10) with massive periaortic metastases. Only 10% (1/10) of patients whose tumor extended to the L1-2 level survived 5 years, compared with 31% (9/29) of those whose disease extended no higher than the L3-4 level. The periaortic failure rates correlated to some extent with the dose delivered through extended fields, although the difference was not statistically significant. Only 8% (1/13) of those who had undergone extraperitoneal lymphadenectomies developed small bowel complications, compared with 25% (7/29) of those who had had transperitoneal lymphadenectomies. The incidence of small bowel obstruction was 8% (1/13) following periaortic doses of 4000-4500 cGy, 10% (1/10) after 5000 cGy, and 32% (6/19) after approximately 5500 cGy. From this, we concluded that the subset of patients who would benefit most from extended field irradiation are those in whom the residual disease in the periaortic area measures less than 2 cm in size at the time of treatment, whose disease extends no higher than L3, and whose cancer within the pelvis has a reasonable chance of control with standard radiation therapy techniques. PMID- 1612951 TI - Postoperative radiotherapy of carcinoma in bilharzial bladder: improved disease free survival through improving local control. AB - Two hundred thirty-six patients with T3 bladder cancer who survived radical surgery and proved to have P3a, P3b, or P4a tumors were randomized in two phases into three groups: (a) no further treatment (83 patients); (b) postoperative radiotherapy multiple daily fractionation (MDF), using 3 daily fractions of 1.25 Gy each, with 3 hr between fractions, up to a total dose of 37.5 Gy in 12 days (75 patients); and (c) postoperative radiotherapy conventional fractionation (CF), for a total dose of 50 Gy/5 weeks (78 patients). The tolerance of the patients to postoperative radiotherapy was quite acceptable, with equal acute reactions in MDF and CF groups. The 5-year disease-free survival (DFS) rates amounted to 49 and 44% in MDF and CF postoperative radiotherapy groups, respectively, compared to 25% in the cystectomy-alone group. The 5-year local control rates were 87% and 93% for those treated with multiple daily fractionation and conventional fractionation while it was 50% in the surgery alone group. The therapeutic benefit of postoperative irradiation was consistent for all tumor types, histological grades, and pathological stages for both the disease-free survival and local control. Patients with nodal metastases demonstrated lower recurrence rates in the postoperative radiotherapy groups, but this was not associated with improved disease-free survival. Multivariate analysis using the Cox Model confirmed these results. The independent prognostic factors affecting both disease-free survival and local control were the addition of postoperative radiotherapy, the nodal status, the pathological stage, and the tumor grade. Late complications of radiotherapy in the skin, small intestine, rectum, and the anastomotic site of the urinary division were lower with MDF than with conventional fractionation. PMID- 1612952 TI - Radiation therapy for diabetes insipidus caused by Langerhans cell histiocytosis. AB - Hypothalamic-pituitary radiation therapy has been the standard treatment for the diabetes insipidus of Langerhans cell histiocytosis. The goal of this study was to assess the role of radiation therapy in Langerhans cell histiocytosis associated diabetes insipidus and to compare the results with nonirradiated controls. Forty-seven patients with pathologically confirmed Langerhans cell histiocytosis were diagnosed with diabetes insipidus between 1950 and 1989 and were treated at the Mayo Clinic. These patients were divided into two groups on the basis of treatment for the diabetes insipidus: The first group (radiation group) included 30 patients (28 of whom were evaluable for response) who received hypothalamic-pituitary radiation therapy, and the second group (control group) included 17 patients who did not. A partial response to treatment was defined as a reduction in vasopressin dosage or improvement in computed tomography (CT) or magnetic resonance imaging (MRI). A complete response was defined as no further need for vasopressin therapy or normalization of CT or MRI. End points analyzed included treatment response, patient characteristics, morbidity, dose-response relationship, and survival. Patient characteristics of the two groups were similar except for age and lung involvement, both of which were significantly less in the radiation group. Thirty-six percent of patients (10 of 28) in the radiation group responded to hypothalamic-pituitary radiation therapy (22% complete response and 14% partial response), whereas none in the control group responded. Five of the six complete responders were irradiated within 14 days of the diagnosis of diabetes insipidus. The mean dose used in the responding and nonresponding patients was 11.2 and 10 Gy, respectively. Three of five patients (60%) treated with more than 15 Gy responded compared to seven of 23 (30%) treated with less than 15 Gy. Eight of the 10 responders (80%), compared to 16 of 35 nonresponders (46%), were female. Only one in 20 patients with concomitant lung histiocytosis responded. Complications of therapy may include insufficiency in other hypothalamic-pituitary axes in the treated patients. Actuarial survivals at 5, 10, 20, and 40 years for the entire group were 80%, 78%, 75%, and 65%, respectively, with a median follow-up in living patients of 14.7 years. PMID- 1612954 TI - Pathology of radiation injury to the canine spinal cord. AB - The histopathologic response of the canine spinal cord to fractionated doses of radiation was investigated. Forty-two dogs received 0, 44, 52, 60, or 68 Gy in 4 Gy fractions to the thoracic spinal cord. Dogs were evaluated for neurologic signs and were observed for 1 or 2 years after irradiation. Six major lesion types were observed; five in the irradiated spinal cord and one in irradiated dorsal root ganglia. The three most severe spinal cord lesions were white matter necrosis, massive hemorrhage, and segmental parenchymal atrophy which had an ED50 of 56.9 Gy (51.3-63.3 Gy 95% CI) in 4 Gy fractions. These lesions were consistently associated with abnormal neurologic signs. Radiation damage to the vasculature was the most likely cause of these three lesions. The two less severe spinal cord lesions were focal fiber loss, which had an ED50 of 49.5 Gy (44.8 53.6 Gy 95% CI) in 4 gy fractions and scattered white matter vacuolation that occurred at all doses. These less severe lesions were not consistently associated with neurologic signs and indicated the presence of residual damage that may occur after lower doses of radiation. Radiation damage to glial cells, axons, and/or vasculature were possible causes of these lesions. In the irradiated dorsal root ganglia, affected sensory neurons contained large intracytoplasmic vacuoles, and there was loss of neurons and satellite cells. Such alterations could affect sensory function. The dog is a good model for spinal cord irradiation studies as tolerance doses for lesions causing clinical signs are close to the estimated tolerance doses for humans, and studies involving volume and long-term observation can be done. PMID- 1612953 TI - Pterygium treated with excision and postoperative beta irradiation. AB - A retrospective study was done of 338 patients with pterygia treated between October 1974 and May 1990. These patients resided in the desert of the southwestern United States, where the hot, dry, dusty climate is thought to predispose to pterygium formation and subsequent recurrence. The pterygia were excised, and the administration of beta irradiation was initiated within 24 hr of surgery. Sixteen percent of the pterygia were recurrent. Ninety-five percent of the beta irradiation prescriptions consisted of 3 weekly 800 cGy fractions. For patients with a minimum of 6 months follow-up, the crude local control rate was 225/258 (88%). The Kaplan-Meier estimate of the 5-year local control rate was 84% (95% confidence interval: 79-89%). Ten of 33 recurrences were diagnosed within 6 months, and 32/33 recurrences were diagnosed within 5 years of treatment. Previously untreated pterygia were controlled more easily than were recurrent pterygia (p = 0.005). In 86% of the cases, patients judged the cosmetic results to be satisfactory. No severe complications developed. This study and others, when compared with studies involving excision alone, suggest that postoperative beta irradiation reduces the likelihood for pterygium recurrence. When the beta irradiation is fractionated, satisfactory cosmetic results can be achieved with low morbidity. PMID- 1612955 TI - Hypobaric hypoxia: a method for testing bioreductive drugs in vivo. AB - Hypobaric hypoxia has been used to induce tumor hypoxia for in vivo comparison of the anti-tumor effects of the bioreductive agents SR 4233 (3-amino-1,2,4 benzotriazine-1,4-dioxide), RSU 1069 (1(2-nitro-1-imidazolyl)-3-aziridino-2 propanol), and Nitromin (methylbis(2-chloroethyl)amine N-oxide). BDF mice bearing the T50/80 mammary carcinoma were treated with these agents over a range of doses under normobaric (oxic) and hypobaric (hypoxic) conditions. The time taken for the tumor to double treatment volume (volume doubling time) was used as a measure of anti-tumor effect. Volume doubling time was plotted against log dose and dose response curves were fitted. A dose enhancement ratio (the ratio of drug doses required to give an equivalent anti-tumor effect under oxic and hypoxic conditions) was determined. The dose enhancement ratios for SR 4233 and RSU 1069 were 8.8 and 8.5, respectively, showing that these agents had an equivalent and substantial enhancement of their cytotoxicity when combined with hypobaric hypoxia. For Nitromin, no significant dose response effect was obtained under oxic conditions precluding the calculation of the dose enhancement ratio. SR 4233 was found to have increased systemic toxicity when combined with hypobaric hypoxia, suggesting that it is more readily activated than the other drugs tested. This in vivo test system will allow determination of the dose enhancement ratio for novel bioreductive agents and facilitate their comparison. PMID- 1612956 TI - Energy status in the murine FSaII and MCaIV tumors under aerobic and hypoxic conditions: an in-vivo and in-vitro analysis. AB - The relationship between energy status and hypoxia was examined in two murine tumors with substantially different hypoxic cell fractions in situ and in cells derived from these tumors in vitro. Parameters of tumor energy status were NTP/Pi and PCr/Pi obtained by 31P-NMR spectroscopy and adenylate energy charge and energy status obtained by high-pressure liquid chromatographic analysis of tumor extracts. Adenylate energy charge and rates of high-energy phosphate degradation were determined on cells obtained from both tumor types (MCaIV and FSaII) under identical nutrient and oxygen conditions, that is, air and nitrogen for various durations (0-6 hr). No consistent or substantial differences were noted in the various parameters of tumor energy status obtained by nuclear magnetic resonance analysis or analysis of tumor extracts, even though the MCaIV contains a substantially larger hypoxic fraction (49% vs 12%). Under in vitro conditions, the two cell lines exhibited different responses to oxygen deprivation, the MCaIV being substantially more refractory to energy changes secondary to hypoxia. Noting with caution that this study is based on only two tumor types, our results suggest that differences in cellular capacity for energy maintenance preclude quantitative inferences regarding tumor oxygen status from energy status between tumor types. PMID- 1612958 TI - The response of murine B-16 melanoma to fractionated doses of pions. AB - The relative biological effectiveness (RBE) of pions has been studied in mouse B 16 melanoma transplanted into C57BL/6 mice. To determine the RBE at both high and low doses per fraction, a range of fractionation schedules was used, with 1, 4 and 10 fractions. The reference 250 kV X ray dose rate was 1.5 Gy/min which was much higher than the dose rate of pions (0.25 Gy/min). The RBE varied depending on the number of fractions and, within the same fractionation schedule, also on the dose per fraction. The RBE ranged from 1.15 for single fractions at 12.5 days of growth delay, to 1.80 for 10 fractions at 5 days of growth delay, which was determined by the time taken for the tumors to reach 5 times the average of their original volume. RBEs at the iso-effect level of 10 days growth delay were 1.20, 1.29 and 1.62 for single, 4 fractions and 10 fractions, respectively. RBE values were influenced by both the number of fractions and the dose per fraction, that is, the larger the number of fractions and the smaller the dose per fraction, the larger the value of RBE. In comparison with RBE of normal mouse skin, it was suggested that pion therapy may provide advantage over conventional photontherapy for radioresistant tumors such as this melanoma with the maximum therapeutic gain factor of 1.2. alpha/beta ratios for B-16 melanoma were also obtained from the 10 day growth delay iso-effect curve, and were 10.5 Gy and 32.6 Gy for X ray and pions, respectively. PMID- 1612957 TI - The development of A [211At]-astatinated endoradiotherapeutic drug: Part I. Localization by alpha-particle autoradiography in a murine tumor model. AB - Alpha-particle track autoradiography has been used to define the in vivo cellular and intracellular distribution of radioactivity from the potential high linear energy transfer endoradiotherapeutic drug, 6-[211At]-astato-2-methyl-1,4 naphthoquinol bis(diphosphate) in tumor and relevant critical normal tissues of mice bearing a transplanted murine rectal carcinoma. A strikingly selective uptake of this compound into tumor cells, particularly into specific tumor cell nuclei, has been demonstrated. Its localization in certain tumor cells appears to depend on the presence of an onco-product, in this case an alkaline phosphatase isoenzyme, which is synthesized in some tumor cells and to which the compound targets. In curable tumors, it selectively concentrates in cells which may be regarded as tumor stem cells. There is low uptake into normal cells, particularly those in bone marrow, colon, and lung, where its sequestration is mainly extranuclear. PMID- 1612959 TI - Reduction of pain and local complications when buffered lidocaine solution is used as a local anesthetic in conjunction with hyperthermia treatments: results of a randomized trial. AB - Unbuffered lidocaine (pH = 6.5) is commonly employed as a local anesthetic prior to transcutaneous placement of catheters for use in temperature monitoring during hyperthermia treatments. The most frequent complaint associated with this procedure is stinging or burning pain at the injection site. Tender firm subcutaneous nodules at sites of lidocaine infiltration for catheter placement have also been noted in fields treated with radiation and hyperthermia. A reduction in the pain associated with lidocaine infiltration has been reported by the use of alkalinized (buffered) local anesthetic solutions. To confirm this finding in patients treated with hyperthermia for superficially-located tumors, a randomized prospective double blind trial comparing unbuffered (pH 6.5) and buffered (pH 7.3) 2% lidocaine (without epinephrine) was undertaken. Between March and October 1990, a total of 54 hyperthermia treatment fields were each randomized to buffered or unbuffered lidocaine to be used at the time of all catheter placements (146 placements). Patients were scored both for the pain noted during the infiltration of lidocaine and the pain noted with subsequent catheter placement. In addition, the development of subcutaneous nodules at the sites of catheter placement was monitored at the time of 3-week follow-up. Follow up was available for all but two fields. Treatment fields that received the buffered anesthetic had a statistically significant reduction in the pain associated with infiltration of lidocaine (p less than 0.05) without any compromise in its therapeutic efficacy as observed on a linear Visual Analog Scale. Furthermore, the incidence of subcutaneous nodules was lower in the fields treated with the buffered solution (1/23 vs 7/29, p = 0.05 for buffered and unbuffered solutions, respectively). The results of this trial support the use of buffered lidocaine prior to catheter placement for hyperthermia treatments as a method of reducing pain at infiltration and the subsequent development of subcutaneous nodules. PMID- 1612960 TI - Enhancement of misonidazole chemosensitization effect by mild local hyperthermia. AB - In an attempt to increase the chemosensitization effect of the alkylating agents 1,3 bis(2-chloroethyl)-1-nitrosourea (BCNU) and cyclophosphamide (CY), by misonidazole (MISO) at the tumor site, mild hyperthermic treatment (41.5 degrees C, 1 hr) was applied at various administration sequences. C3Hf/Sed mice bearing subcutaneous FSa-II tumors in the foot were used for a tumor growth time assay. Local hyperthermic treatment increased the antitumor activities of BCNU and CY by 1.4 and 2.4 fold, respectively. MISO at 2.5 mmole/kg potentiated the antitumor activities of BCNU, but not CY, at normal body temperature. There were no significant improvement of MISO chemosensitization when heat was given before the administration of BCNU and CY. However, a significant enhancement of chemosensitization was observed when heat was given after the administration of MISO and the alkylating agents. Enhancement ratios of about 2.4 and 4.7 were observed with BCNU and CY, respectively. There may be two mechanisms responsible for this thermal enhancement. First, the MISO pre-incubation time that was required for the expression of chemosensitization effect decreased substantially at elevated temperatures. This hypothesis was supported by the pharmacokinetic studies that MISO was rapidly eliminated from tumors in the first 10 min during the local heat treatment and remained at a plateau with a concentration of about 5-fold less than the peak MISO concentration in the control tumors. This rapid elimination might result from the increase in the rate of hypoxic metabolism of MISO in heated tumors. Second, heat may increase the MISO-alkylating agent interactions, which are independent of pre-incubation time. This effect was especially pronounced in CY because pre-incubation-induced chemosensitization of CY in unheated tumor was insignificant in this study. The significant improvement of MISO chemosensitization at moderately elevated temperatures can be useful clinically in combined hyperthermia and chemotherapy treatment. PMID- 1612961 TI - Episcleral plaque thermoradiotherapy in patients with choroidal melanoma. AB - From 1988 to 1991, 21 patients with uveal melanoma were treated in a Phase I study with episcleral plaque radiotherapy (EPRT). This irradiation was combined with localized current field episcleral hyperthermia (LCFHT). Tumor stage was: T3 = 15 (71%) and T2 = 6 (29%). Follow-up ranged from 2 to 42 months (mean 9.2 months). EPRT was given using custom built I-125 gold plaques. Radiation doses to the tumor apex ranged from 13 to 123 Gy (mean dose 70.0 Gy) given at a mean dose rate of 55 cGy/hr. LCFHT was given with 500 KHz frequency for 45 min immediately before EPRT. The temperature was controlled on the scleral surface using four thermocouples. T mean ranged from 42.5 degrees C to 45 degrees C +/- 0.5 degrees C (mean 43.4 degrees C). The study patients showed rapid tumor necrosis. A 25% mean decrease of apical tumor dimension was noted, p = 0.0007. At least ambulatory vision (greater than 5/200) was maintained by 17/21 (81%) patients. Visual acuity was seen to improve greater than 6 months post-plaque therapy in 10 (48%) study patients. This was following an intermediate decrease in visual acuity. Severe complications, including large hemorrhagic retinal detachment and large vitreous hemorrhage, were seen in two (9.5%) of the early study patients. A mean scleral temperature reduction to less than or equal to 44 degrees C +/- 0.5 degrees C resulted in good treatment tolerance and a lack of serious complications in subsequently treated patients. A Phase II prospective randomized trial comparing LCFHT with 60 versus 80 Gy EPRT dose to the tumor apex is currently being activated for patients with choroidal melanoma. PMID- 1612962 TI - Improved methods for determination of variability in patient positioning for radiation therapy using simulation and serial portal film measurements. AB - Variability in patient positioning was determined by analyzing simulation and portal film measurements for 318 portals in 51 patients treated with external beam radiotherapy to the head and neck. Several indicators of error in patient positioning were examined: random error, a measure of the deviation of all portal films from the average portal film position, systematic error, a measure of the difference between the average portal film and the simulation film, and total uncertainty, a measure of the overall deviation, including both random and systematic uncertainties. The median differences noted were 0.4 cm, 0.6 cm, and 0.7 cm, for Random Error, Systematic Error, and Total Uncertainty, respectively. The treatment fields analyzed in this study show a substantial treatment-to treatment and simulation-to-treatment variability in patient positioning. The methods described provide an improved means for the systematic analysis of variability in patient positioning. PMID- 1612963 TI - Microdosimetric single event spectra of Ytterbium-169 compared with commonly used brachytherapy sources and teletherapy beams. AB - Ytterbium-169 has been developed as a possible replacement for Iridium-192 and Iodine-125. The Theory of Dual Radiation Action predicts that the initial slope of the cell survival curve and therefore the relative biological effect at low dose rate is proportional to dose average lineal energy, yd, which is the microscopic analog of the dose average linear energy transferred. The quality factor used in radiation protection has been shown to be a function of the frequency average lineal energy, yf. Single event microdosimetric spectra for 60Co, 137Cs, 192Ir, 125I and 169Yb were measured in air and at several depths in phantom with a Rossi proportional counter. These spectra show marked differences between sources. The microscopic analogs of the track average and dose average LET, (yd and yf, respectively) differ between isotopes by factors of two or even higher in comparison to megavoltage electron beams. These yd's and yf's for 169Yb are consistently higher when compared to 60Co or 137Cs but are approximately equal to those for 125I. Values of yf and yd for 192Ir are intermediate between 60Co and 169Yb. The Theory of Dual Radiation Action predicts a low dose rate RBE (assuming a 1 micron effective site diameter) compared to 60Co (in air) of: 1.00 for 137Cs, 1.29 for 192Ir, 1.60 for 169Yb and 1.77 for 125I. PMID- 1612964 TI - A prototype radiation oncology clinical information processing system on a personal computer (network). AB - Software has been developed that facilitates prospective computer entry of the clinical contents of a radiation oncology chart in a way that assists in retrospective analyses. This software, which has been operational since 1988, now contains detailed clinical information on over 500 patients treated since that time, and limited information on over 3000 children treated since 1970. The system has been programmed using the FoxPro database management system, and may be run on an IBM compatible or Macintosh personal computer either alone or in a networked environment. Information is transcribed as routine patient dictations that require no extra personnel for entry. Standard printouts are the conventional notes compatible with the existing paper chart. Exportation of patient records is facilitated by means of built-in facsimile. The software has been designed to generate detailed reports automatically, including the statuses of selected patients or groups, lists of those who are behind in follow-up, and reports of specific events (e.g., mucositis) that occur before, during, or after therapy using free-text searches. Complete reconstruction of the patient's clinical radiation oncology chart is also included. Other abilities include calculation of Kaplan-Meier survival, relapse-free survival, and local control rates, statistical comparison between survival curves, and radiation dose response. Exportation of data to statistical and graphics packages is also possible. For pediatric patients, a program to predict stature loss has been incorporated. Use of this system can enhance one's ability not only to follow patients but also to monitor and report their outcome continually. With the need to report institutional experiences and increasing demands to monitor quality assurance, such a system can be of great benefit. PMID- 1612966 TI - Improved pain management with daily nursing intervention during radiation therapy for head and neck carcinoma. AB - This study evaluated the response to a defined mouth care and analgesic treatment protocol for oropharyngeal mucositis in patients undergoing radiation therapy for head and neck carcinoma. Nineteen patients completed a 15 question pain survey before each radiation treatment. Patients were given instructions on the use of mouthwashes and a three-step analgesic protocol: acetaminophen, acetaminophen with codeine suspension, and oral morphine (20 mg/mL) for mild, moderate, and severe pain, respectively. Patients were seen daily by a radiation therapy nurse who reviewed the survey and prompt changes in the prescribed analgesic regimen were then made by a physician. Marked differences in control of pain related to radiation mucositis were observed when compared to patients from our prior study who used the same daily survey but had only sporadic nursing intervention and no analgesic protocol. Patients having daily nursing intervention reported fewer days of moderate/severe pain, had less pain throughout the day, and noted less disturbance in sleep, eating, and energy level. Weight loss of greater than 5 kg was noted in only three patients. Analgesics were used on 77% of treatment days and relieved all or most of the pain in 94% of these days. Daily review of a symptom survey by a radiation therapy nurse, combined with a well-defined strategy for mouth care, and analgesics results in improved pain management of radiation induced oropharyngeal mucositis because of prompt attention to patient needs. Future trials should incorporate defined strategies for oral care and analgesic use to control for possible bias in assessing efficacy. PMID- 1612965 TI - Devices valuable in head and neck radiotherapy. AB - Normal tissue reactions limit the use of radiotherapy in the management of patients with head and neck neoplasms. Customized intraoral stents can help prevent unnecessary irradiation of various normal tissues thus reducing severity of reactions. Two basic types of devices, referred to as shielding and positional stents, are presented. The fabrication and the application of such devices are illustrated through five case reports. Recommendations on use of these tools and the possibility of combining these means with methods to improve dose distribution within the target volume containing air gaps are provided. Close collaboration between the attending radiotherapist and dentist is essential for designing appropriate devices for individual patients. However, when properly designed and used, these stents are effective in reducing treatment morbidity. PMID- 1612967 TI - Local control and patient survival. AB - Consideration is given to the concern that future improvements in radiation therapy which achieve increases of local control probabilities will fail to yield gains in survival, in that the new local control patients will ultimately fail because of the development of distant metastasis. The concept is that the local failure merely represents a marker of the exceptionally malignant nature of the tumor; hence, elimination of the local tumor will not affect the ultimate outcome, viz distant failure. This would mean that all tumors which fail locally after the current best radiation therapy will have established distant metastasis (subclinical) at the time of treatment of the primary tumor in stage M0 patients. Thus, a more effective local treatment would not impact on the ultimate fate of the patient. Several lines of evidence are discussed which document that tumor free survival is greater after treatment which yields higher local control probabilities than those achieved by conventional external beam radiation therapy. That is, not all of the new local control patients develop distant metastasis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1612968 TI - Pulsed brachytherapy: the conditions for no significant loss of therapeutic ratio compared with traditional low dose rate brachytherapy. AB - Pulsed brachytherapy consists of using a stronger radiation source than for traditional low dose-rate brachytherapy, but giving a series of short exposures of 10 to 30 min in every hour, to approximately the same total dose in the same overall time as with the low dose-rate. Calculations based on the linear quadratic model, in which the beta x dose squared component only is assumed to be repairable, and at a monoexponential rate, show that there is no significant loss of therapeutic ratio, defined as tumor damage for a given level of late damage. Some loss of therapeutic ratio would in principle be expected when dose rates are increased, but, in the presently proposed applications, there are so many small pulses (fractions at medium or low dose-rate) that even though repair is not usually complete between them, the relative increase of late damage (in units proportional to log cell kill) is less than 10% more than the increase of tumor damage, except in unlikely conditions that we define. Although these calculations suggest that pulsed brachytherapy should be safe for pulse repetition frequencies up to about 2 hr, using dose rates not exceeding about 3 Gy/hr, we discuss the radiobiological reservations and the limitations of such calculations. PMID- 1612969 TI - Induction chemotherapy in advanced head and neck tumors. PMID- 1612970 TI - Treatment selection for "bulky" carcinoma of the endocervix. PMID- 1612971 TI - Radiation therapy in children: continued need to assess risk versus gain. PMID- 1612972 TI - Treatment of pediatric cancer: risk versus gain--which side of the fence are we on? PMID- 1612973 TI - Response to editorial by Dr. Liu: Universally accepted staging system is urgently needed for better sharing of experience in the clinical management of nasopharyngeal carcinoma. PMID- 1612974 TI - Experience with continuous hyperfractionated accelerated radiotherapy (CHART) PMID- 1612975 TI - Influence of renal shielding on the incidence of late renal dysfunction associated with T-lymphocyte deplete bone marrow transplantation in adult patients. AB - Late renal dysfunction following allogeneic bone marrow transplantation has been described by a number of centers including our own. Total body irradiation appears to play a major causative role in the development of this syndrome. In an effort to decrease the incidence of this renal toxicity we have added customized partial transmission renal blocking to our total body irradiation regimen. This partial renal shielding decreases the total dose to the kidneys from 14 Gy to 12 Gy. This report compares 71 adult patients who have received total body irradiation associated with bone marrow transplantation using renal shielding with 72 adult patients who were treated without the shielding; all of the patients have survived a minimum of 100 days post-BMT. Eighteen months following BMT, 26% of patients who did not have renal shielding have developed late renal dysfunction compared to only 6% of patients with renal shielding (p less than .05). Median follow-up in the nonblocked patients is 536 days post-transplant versus 341 days for the blocked patients. This added renal blocking has not adversely affected engraftment rates or relapse rates to date. Customized renal shielding as part of 14 gray total body irradiation in preparation for bone marrow transplantation appears to have decreased the incidence of late renal dysfunction in this group of adult patients and should be considered for all patients undergoing total body irradiation in conjunction with bone marrow transplantation. PMID- 1612976 TI - Opinions on responsibility toward wildlife. PMID- 1612977 TI - Over-the-counter pet vaccines: legal, but inadvisable. PMID- 1612978 TI - Council and advisory committee support initiative to amend Food, Drug, and Cosmetic Act. PMID- 1612979 TI - Don't mess with success. PMID- 1612980 TI - Animal research and veterinary medical research funding: a vision of the future. PMID- 1612981 TI - What's a new graduate worth? PMID- 1612982 TI - Effect of topically administered atropine on tear production in dogs. AB - Baseline tear production values were established for both eyes of 19 dogs, using the Schirmer tear test. Atropine sulfate, 1% solution, was administered topically in the left eye of each dog once daily for 14 days. Tear production was then determined for both eyes at 15, 30, 60, 120, 180, 240, and 300 minutes, and 3, 6, 9, 12, and 15 days. A final Schirmer tear test reading was obtained for each eye 5 weeks after the last atropine treatment to check for the possibility of prolonged effect. Both eyes had statistically significant (P less than 0.05) decrease in tear production that was most marked at 120 minutes after atropine instillation, then returned to baseline values by 300 minutes after instillation. Although atropine was placed in the left eye only, statistically significant difference was not apparent in Schirmer tear test values between the left and right eyes. Tear production continued to decrease in both eyes over time, becoming statistically significant (P less than 0.05) on day 9. However, on days 12 and 15, tear production in the untreated eye plateaued, but that in the treated eye continued to decrease. Five weeks after the last treatment with atropine, both eyes still had a statistically significant (P less than 0.05) decrease in tear production, although Schirmer tear test values had increased from day-15 values and appeared to be returning to baseline. Association was not evident between age or body weight and magnitude of response to topically applied atropine. PMID- 1612983 TI - Familial cataracts and concurrent ocular anomalies in chow chows. AB - A closely inbred line of Chow Chows affected with congenital cataracts was studied. Sixteen dogs were examined including 1 adult male, 2 adult females, and 13 pups. Twelve of the pups were from 6 different litters, out of 6 different bitches, all sired by 1 adult male. The exact relationship of the thirteenth pup was undetermined. Clinical evaluation included slit-lamp biomicroscopy, biomicroscopic photography, and indirect ophthalmoscopy. Clinical appearance of the cataracts was variable, ranging from incipient nuclear or capsular lesions to advanced cortical opacity. The lens nucleus was most consistently affected, with variable involvement of the lens cortex. Concurrent ocular anomalies of some eyes included wandering nystagmus, entropion, microphthalmia, persistent pupillary membrane remnants, and multifocal retinal folds. A correlation was not apparent between the character or severity of the cataracts and the finding of the other anomalies. Histologic examination of 12 lenses revealed posterior displacement of the lens nucleus, retained lens epithelial cell nuclei in the nuclear and cortical lens, anterior capsular irregularity and duplication, anterior lens epithelial duplication, and posterior subcapsular migration of epithelium. The high incidence of cataract in this family of Chow Chows suggested an inherited defect, although the inheritance pattern was undetermined. PMID- 1612984 TI - Relationship to growth performance of pneumonia and atrophic rhinitis lesions detected in pigs at slaughter among four seasons. AB - A commercial swine herd was selected for study, because pigs at slaughter repeatedly had lung lesions consistent with enzootic pneumonia and had snout lesions typical of atrophic rhinitis. Pigs born during various seasons of the year were allotted to 4 investigations and were evaluated from birth to slaughter. Individual lungs and snouts were identified and collected at the slaughter plant and later examined for gross lesions of bronchopneumonia and atrophic rhinitis, respectively. Each lesion was scored, and the following comparisons were made within investigations: prevalence and mean scores for lung lesions; prevalence and mean grades for snout lesions; correlations between lung lesion scores and growth indicators; correlations between snout lesion grades and growth indicators; and correlations between lung lesion scores and snout grade scores. Included in the growth indicators were average daily gain during the growing phase, average daily gain during the finishing phase, average daily gain during growing and finishing phases, and days to attain 104.5 kg of body weight. Prevalence of lung or snout lesions, mean values for lung lesion scores, mean values for snout lesion grades, and mean values for the various growth indicators were tested for statistical differences among the 4 investigations. Prevalence of lung lesions was highest (96%) for winter-slaughtered and lowest (81%) for autumn slaughtered pigs. Mean scores for lung lesions were 7% (summer), 5% (autumn), 9% (winter), and 16% (spring). Prevalence of snout lesions was highest (85%) for spring-slaughtered pigs and lowest (42%) for autumn-slaughtered pigs.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1612985 TI - Gastric extramedullary plasmacytoma in a dog. AB - A 10-year-old mixed-breed dog was examined because of a 6-week history of daily vomiting and sporadic diarrhea. On gastroscopy, a crateriform mass was observed on the greater curvature of the stomach. Partial gastrectomy and lymphadenectomy of a large mesenteric lymph node was performed. Gastric plasmacytoma with lymph node metastasis was diagnosed by histologic and immunoperoxidase methods, and chemotherapy was initiated with doxorubicin hydrochloride and diphenhydramine hydrochloride. The dog remains clinically normal 30 months after initial diagnosis. Although gastric plasmacytomas are rare in dogs, long-term survival appears to be better with this disease than with other types of gastric neoplasia. PMID- 1612987 TI - Scintigraphic evaluation of tissue viability after gunshot injury in a dog. AB - Triple-phase bone scintigraphy was used to evaluate tissue viability in the forelimb of a dog after gunshot injury. This technique was reliable, noninvasive, and easily performed. It was used to complement radiography by providing functional, rather than structural, assessment of tissues on the basis of regional vascular patterns. In this dog, vascular impairment caused by trauma appeared as photopenic or "cold" spots during immediate (vascular), soft tissue and bone phases of the scintigraphic study. On the basis of gross morphologic and scintigraphic findings, forelimb amputation was performed. PMID- 1612986 TI - Squamous cell carcinoma of the corneoscleral limbus in a dog. AB - Squamous cell carcinoma is an uncommon tumor of the cornea in dogs. A 12-year-old Shih Tzu with a history of chronic keratoconjunctivitis sicca was diagnosed as having squamous cell carcinoma of the corneoscleral limbus. The lesion was treated by surgical resection and cryotherapy. One year after surgery, multiple tumors, apparently unrelated to the first tumor, appeared on the same cornea. Keratoconjunctivitis sicca may have predisposed the dog to corneal squamous cell carcinoma development. PMID- 1612989 TI - Acute overdose of levothyroxine in a dog. AB - An overdose of up to 850 levothyroxine sodium tablets (0.2 mg) in a healthy 6 year-old 16.8-kg dog induced an episode of vomiting and hippus within 9 hours of ingestion. The dog was treated with activated charcoal and saline (magnesium sulfate) cathartic. Initially the serum concentration of thyroxine (T4) 4,900.9 nmol/L. On the second day, serum concentration of triiodothyronine (T3) was 5.3 nmol/L. Serum T4 concentration decreased slowly and was not determined to be normal until day 36. Serum T3 concentration was found to be normal on day 6. Serum alanine transaminase activity peaked on day 6 at 345 U/L. Significant abnormalities were not found during the following 36 days. Clinical signs of thyroid hormone toxicosis in dogs and cats include hyperactivity, lethargy, tachycardia, tachypnea, dyspnea, abnormal pupillary light reflexes, vomiting, and diarrhea. High overdoses of levothyroxine sodium in dogs should be managed by initial decontamination and administration of activated charcoal with a cathartic followed by supportive care. PMID- 1612988 TI - Calcium phosphate urolithiasis and renal dysplasia in a young dog. AB - Calcium phosphate urolithiasis and bilateral renal dysplasia was diagnosed in an 8-week-old Border Terrier with a history of urine dribbling, which had been observed from the time of birth. Most reported cases of calcium phosphate urolithiasis are secondary to hypercalcemic disorders, but this was not detected. In addition, despite renal dysplasia, there was no evidence of renal failure. After cystotomy and calculus removal, the dog has remained clinically normal. PMID- 1612990 TI - Diagnosis of ruptured urinary bladder in a foal by the identification of calcium carbonate crystals in the peritoneal fluid. AB - A 3-day-old Quarter Horse colt was examined because of signs of severe depression, discomfort, and abdominal straining. The foal seemed disoriented, and the abdomen was tense and distended ventrally. The differential diagnoses included ruptured urinary bladder, retained meconium, septicemia/bacteremia, and neonatal maladjustment syndrome. Serum biochemical analysis revealed marked hyponatremia, hypochloremia, and moderate hyperkalemia, as well as mildly high urea, creatinine, and phosphorus concentrations. The primary differential diagnosis at this time was ruptured urinary bladder. Abdominocentesis was performed to confirm this diagnosis. Microscopic examination of abdominal fluid revealed calcium carbonate crystals, which originated from the urine of the foal. Biochemical analysis also confirmed the diagnosis of ruptured urinary bladder, because the ratio of peritoneal fluid creatinine to serum creatinine was 2.8:1. The foal died before surgical correction could be attempted. PMID- 1612991 TI - Eosinophilic gastroenteritis with encapsulated nematodes in a horse. AB - A 3-year-old Quarter Horse gelding admitted for evaluation of weight loss, signs of depression, and dermatitis of the coronary bands was found to have eosinophilic gastroenteritis. Intralesional nematodes identified as Strongylus edentatus were seen in multiple microscopic sections of the small colon, suggesting a parasitic cause of the disease. PMID- 1612992 TI - Septic cholangitis and peritonitis in a gelding. AB - An 8-year-old Arabian gelding with septic cholangitis and peritonitis was successfully treated with trimethoprim/sulfadiazine. The gelding was referred for evaluation of signs of abdominal pain, icterus, fever, and weight loss. Peritoneal fluid analysis revealed septic and suppurative peritonitis. Culture of the peritoneal fluid yielded Escherichia coli and Klebsiella pneumoniae, which were sensitive to trimethoprim/sulfadiazine. On the basis of results of hepatic ultrasonography, a diagnosis of septic cholangitis also was made. The horse was treated with 30 mg of trimethoprim/sulfadiazine/kg, PO, q 12 h for approximately 6 weeks. The horse improved steadily, and telephone follow-up with the owner 1 year later disclosed that the horse had complete return to normal condition, appetite, and attitude. On the basis of our findings, aggressive, long-term anti inflammatory and antibiotic treatment may result in complete return to health and normal athletic function in horses with septic cholangitis and concurrent septic peritonitis. PMID- 1612994 TI - Congenital parainguinal hernia in a heifer. AB - A 2-day-old heifer was examined for a pendulous mass in the left inguinal region. The calf also had moderate brachygnathia. The mass was determined to be a parainguinal hernia, which was surgically repaired. Parainguinal hernias can be confused with other hernias in the inguinal region. Because of lack of previous reports, the hereditary aspects can only be postulated. PMID- 1612993 TI - Metastatic granulosa cell tumor in a mare. AB - A 5-year-old Quarter Horse mare was referred for evaluation of an acute non weightbearing lameness of the left hind limb in which musculoskeletal abnormalities had not been detected. After admission, the mare had signs of colic. Exploratory laparotomy revealed the left ovary to be large, masses in the left sublumbar space, and diffuse infiltration of the mesentery, omentum, liver, and spleen with variably-sized masses. The mare was euthanatized, and granulosa cell tumor was identified on histologic examination of the left ovary, left sublumbar and cranial thoracic lymph nodes, omentum, mesentery, liver, spleen, and lung. PMID- 1612995 TI - Infertility in a ewe as a result of ovotestis. AB - A ewe with apparently normal estrous cycles was unable to conceive as a result of a single ovotestis. The ovotestis was diagnosed on the basis of results from laparoscopic examination, human chorionic gonadotropin stimulation, and histologic examination of the gonad. The report reinforces the necessity of considering all causes of infertility in affected sheep, and not simply infective causes. PMID- 1612996 TI - Locations and types of neoplasms in immature dogs: 69 cases (1964-1989). AB - Sites, histologic types, and frequencies of neoplasms in immature dogs (less than or equal to 6 months old) were evaluated from data collected over 25 years. The frequencies of neoplasms in immature dogs were compared with those of mature dogs (greater than 6 months old). Of 69 immature dogs with neoplasms, 5 had 2 primary neoplasms each, resulting in a total of 74 neoplasms. The 3 most common sites for neoplasia, in decreasing order, were the hematopoietic system, brain, and skin. Immature dogs were 10.9 times more likely to have a neoplasm located in the brain, compared with mature dogs. Immature dogs also were 3.3 times more likely to have a neoplasm associated with the hematopoietic system, compared with mature dogs. PMID- 1612997 TI - Prevalence of Dirofilaria immitis and Dipetalonema reconditum infection in dogs: 805 cases (1980-1989). AB - Clinical records of 6,977 dogs examined at the small animal clinic of the University of Tennessee College of Veterinary Medicine from January 1980 through December 1989 were analyzed to determine the prevalence and changing frequency of Dirofilaria immitis and Dipetalonema reconditum infection. Using the Knott's test on these dogs, 805 (11.54%) tested positive for microfilariae, with D immitis in 430 dogs (6.16%), and Dip reconditum in 375 dogs (5.37%). Statistical analysis confirmed that the prevalence of D immitis and that of Dip reconditum were essentially equal in the population of dogs included in this study. There was a slight decrease in the prevalence of D immitis over the 10 years examined, but the prevalence of Dip reconditum remained constant. The results were not affected by year-to-year variability in the number of examinations performed. On the basis of our findings, in eastern Tennessee, those veterinarians who diagnose heartworm infection by the presence of microfilariae without differentiating the species involved, risk misdiagnosing 50% of the cases. If the patterns of prevalence seen in recent years continue, the chances of error may actually increase. PMID- 1612998 TI - Correlation between thoracic radiographs and postmortem findings in dogs with hemangiosarcoma: 77 cases (1984-1989). AB - Thoracic radiographic and postmortem findings were compared in dogs with histologically confirmed hemangiosarcoma (HSA). On the basis of results of radiography, a false-negative diagnosis was made for pulmonary HSA in 10 (21.7%) of 46 dogs, and in 26 (53.1%) of 49 dogs for cardiac HSA. The incidence of false negative radiographic diagnosis for pulmonary HSA was lower in dogs when left and right lateral views were obtained. The radiographic sensitivity was 78%, and the negative-predictive value was 74% for pulmonary HSA. The radiographic sensitivity was 47%, and the negative-predictive value was 43% for cardiac HSA. PMID- 1612999 TI - Mycobacterium bovis infection in a captive herd of Sika deer. AB - Infection with Mycobacterium bovis was diagnosed in a small privately owned herd of Sika deer. After postmortem examination of a deer with progressive pulmonary disease, diagnosis of infection with M bovis was confirmed by bacteriologic culture. The 2 remaining deer in this herd were euthanatized, necropsied, and confirmed to be infected with M bovis. Three cats in contact with the deer were also euthanatized and necropsied. One of these cats had lesions suggestive of mycobacterial infection in the colon and mesenteric lymph nodes. Infection of this cat with M bovis was not confirmed by bacterial culture. Mycobacteriosis, infrequently encountered in clinical veterinary practice, may be confused with disease caused by other infective agents or neoplasia. The zoonotic potential of these bacteria and a recent increase in human tuberculosis warrants continued surveillance of companion and food animal populations for mycobacterial infection. PMID- 1613000 TI - What is your diagnosis? Complete avulsion of the mid-cervical portion of the trachea, with approximately 4-cm displacement of the avulsed ends. PMID- 1613001 TI - Myelodysplastic syndromes. PMID- 1613002 TI - Morphology and classification of myelodysplastic syndromes. AB - The FAB classification has provided a common language for clinicians and pathologists in the investigation of myelodysplasia. It has also provided prognostic information, given the excellent correlation between FAB subgroup and survival (see Table 2). Refinements in immunologic and cytogenetic typing should provide further prognostic power and correlation with the underlying biologic processes. PMID- 1613003 TI - Issues in the pathology of the myelodysplastic syndromes. AB - The diagnosis and subclassification of myelodysplastic syndromes (MDS) are usually straightforward if the criteria established by the French-American British Cooperative Group are carefully followed. Some cases can be diagnostically challenging, however. This article discusses some of the special diagnostic problems such as hypocellular MDS, MDS with fibrosis, and cases that show morphologic overlap with myeloproliferative disorders and acute leukemia. Additional problems sometimes encountered in the diagnosis of MDS such as extramedullary disease, associated lymphoproliferative disease, and the 5q syndrome are also reviewed. PMID- 1613004 TI - Cytogenetics. AB - Myelodysplastic syndromes (MDS) for a long time were an ill-defined group of disorders, the true nature of which was largely unknown. Because some patients developed acute leukemia, MDS was considered to be potentially premalignant. Cytogenetic investigations in the early 1970s brought the first clear evidence that these disorders were clonal. Further research has shown that MDS encompasses a number of cytogenetic entities, some of which are associated with clinically distinct disorders. PMID- 1613005 TI - In vitro hematopoiesis in myelodysplasia: liquid and soft-gel culture studies. AB - In vitro clonogenic assays of bone marrow have provided invaluable information about the complex regulatory mechanisms controlling hematopoiesis, both normal and abnormal, and have led to the discovery of colony stimulating factors. Our understanding of the abnormalities of growth and differentiation characterizing the MDS have been advanced largely through use of these assays. Abnormalities commonly seen in cultures of marrow from patients with MDS include decreased or absent colony growth, abortive cluster formation, and defective maturation of cells within the colonies. Although some investigators have defined growth patterns as "leukemic" and "nonleukemic" and have tried to correlate growth patterns with potential for evolution to acute leukemia, these methods are difficult to apply to any given case. Given the wide variety of techniques used to collect cells and the lack of standard sources for stimulating growth factors, the results, not surprisingly, have been inconclusive in predicting both prognosis and progression to acute leukemia. New methods by which clonogenic assays can be standardized, such as purification of the clonogenic cells and use of recombinant growth factors, should allow these assays to advance our understanding of MDS, develop new therapies, and predict responses to therapy in individual patients. PMID- 1613006 TI - Molecular genetic aspects of myelodysplastic syndromes. AB - Myelodysplastic syndromes originate from a pluripotent stem cell. This view, previously suggested by G-6-PD and cytogenetic investigations, has been established unequivocally by X-chromosome inactivation analysis based on DNA polymorphisms and by studies of mutated oncogenes. Two genomic alterations associated with MDS have been analyzed in more detail. Activation of the RAS oncogenes, preferentially N-RAS, is demonstrated in approximately 35% of MDS patients. Mutations in the FMS gene, encoding the CSF-1 receptor, are found in 16% of cases. Interestingly, RAS and FMS mutations are predominantly observed in disorders of myelomonoctic differentiation, i.e., the CMML subtype in MDS and the AML FAB type M4. Moreover, homozygous deletion of the FMS gene may be an important event in the genesis of the MDS variant 5q- syndrome. Preliminary data indicate that defects in tumor-suppressor genes, namely p53, may also contribute to the development of MDS. Different lines of evidence suggest that clinical preleukemia is preceded by a phase in which genetic alterations accumulate without any hematologic change. Cases in point are the detection of RAS and FMS mutations in healthy individuals who had been treated in the past with cytotoxic therapy for lymphoma, the frequent observation of clonal remission in AML patients, or the identification of oncogene mutations in healthy individuals without even a history of malignancy or chemotherapy. Possibly, either germline mutations of oncogenes or tumor-suppressor genes and the process of genomic imprinting may constitute additional factors that predispose hematopoietic stem cells to malignant transformation. Limited as they are, the currently available data suggest that accumulation of genomic lesions, rather than their precise order of development with respect to one another, characterize the multistep process of leukemogenesis in which MDS already represent more advanced stages. The prognostic significance of oncogene mutations in MDS patients is controversially discussed. This issue awaits prospective analyses taking into account the influence of treatment modalities. However, the clinical relevance of molecularly defined parameters has already been established for their use as clonal markers in determining the mode of action and efficiency of different therapeutic approaches. PMID- 1613007 TI - Immunologic abnormalities in myelodysplastic syndromes. AB - In myelodysplastic syndromes, several autoimmune phenomena are more common than expected. Lymphocyte subsets are sometimes abnormal in number and function. Associated lymphoid malignancies and lymphoblastic evolution have occasionally been reported. Molecular studies suggest that the lymphoid system may be involved in the dysplastic process. PMID- 1613008 TI - A guide to risk assessment in the primary myelodysplastic syndrome. AB - The heterogeneity of primary myelodysplastic syndromes, the concentrated efforts of discerning their multistep pathogenesis, and the availability of recombinant hemopoietic growth factors have made these diseases a focus for clinical and scientific research. In order to compare therapeutic modalities in these clinically diverse diseases it is essential to select relatively homogeneous groups of patients based on easily available prognostic features. A guide to risk assessment is outlined in this article with a view to answering the question, "Whom should we treat and when?" PMID- 1613010 TI - Intensive chemotherapy and bone marrow transplantation for myelodysplastic syndromes. AB - In myelodysplastic syndromes (MDS), complete remission rates of acute myelogenous leukemia (AML)-type chemotherapeutic regimens vary widely, ranging from 15% in patients with myelodysplasia after previous cytotoxic therapy to 61% in patients with refractory anemia with an excess of blasts in transformation without previous exposure to leukemogenic chemicals. The duration of remission is usually short, and those that exceed 24 months are unusual. Results of treatment are identical in the different types of MDS. No sufficient data on aggressive therapy are available for refractory anemia and refractory anemia with ringed sideroblasts. Prognostically favorable subgroups of patients are defined by age (below 45 or 50 years), no prior history of cytotoxic drug exposure, and absence of cytogenetic aberrations, especially of chromosomes 5 and/or 7. In contrast to AML-type chemotherapy, allogeneic bone marrow transplantation following high-dose (radio) chemotherapy offers a significantly greater chance of cure with a long term relapse-free survival rate of 30% to 60%. PMID- 1613011 TI - Experience in pediatric myelodysplastic syndromes. AB - Childhood MDS comprises a group of heterogeneous clinical disorders with overlapping features and many similarities to adult MDS. Environmental factors, genetic predisposition, certain viral infections, and impairment of the developing immune system perhaps play a major role in the genesis of the most common disease forms, such as JCMMoL and the monosomy 7 syndrome. One intriguing finding in these disorders is the striking male predominance. Diagnostic difficulties occur because dysplastic manifestations of the hematopoetic systems are usually not as impressive as in adults and because myelodysplastic and myeloproliferative disease forms overlap considerably. Despite these problems, we believe that pediatric cases of MDS should also be classified according to the established FAB classification for MDS. However, as has already been proposed earlier by others, JCMMol clearly should be considered as a specific entity different from the adult form of CMMoL. As has been shown by cell culture studies, JCMMoL is characterized by the presence of neoplastic macrophage/monocyte progenitor cells. These cells produce several factors that result in autostimulation and suppression of normal hematopoiesis. MDS is a highly malignant disease in children and evolves to acute leukemia after a short period. During the early phase of the disease, supportive care is sufficient. If a compatible donor is available, BMT is the treatment of choice and should be performed during the early stage of disease progression after clinical remission is obtained with chemotherapy. If BMT is not feasible, intensive chemotherapy may improve the clinical condition and prolong survival. Preliminary data suggest that the incorporation of hematopoietic growth and/or differentiation factors in chemotherapy and BMT protocols may have some beneficial effects. The only way to accumulate sufficient data on MDS in children with respect to clinical features, prognosis, and efficacy of treatment is to follow a uniform diagnostic and treatment program. To achieve substantial improvements in the management of childhood MDS, multicenter trials will be essential. PMID- 1613012 TI - Japanese experience in the treatment of myelodysplastic syndromes. AB - In spite of the numerous therapeutic attempts cited, the overall results have been unsatisfactory, because responses are usually modest, short in duration, and often associated with considerable toxicity. No treatment has proven superior to conventional supportive care. A marked heterogeneity exists in the clinical manifestations and outcome of MDS on the whole, and even within single subtypes of MDS. The heterogeneity should be taken into account in the selection of therapeutic options. Leukemic transformation and nonleukemic death, notably infections and bleeding, are the two major determinants of prognosis. The risk factors for the two clinical settings are, at least in part, separable. In addition, some patients can survive for more than 5 years. Analysis of the clinical conditions of these long-term survivors suggests that, in a small number of patients, the chance of long-term survival is more likely to be a part of the natural history rather than the result of treatment. Thus, careful evaluation of the initial data is essential in designing treatment for MDS patients so that risks and benefits can be weighed against the possibility of long-term survival. Recombinant hematopoietic growth factors may provide some hope. These biologic factors have considerable advantages over many pharmaceuticals in that they are natural, short-lived, less toxic, and highly effective. In fact, the overall efficacy of CSFs has been outstanding for disorders hitherto viewed as otherwise refractory. Maintenance treatment utilizing these factors in a carefully designed prospective study is urgently needed to determine whether such a treatment modality may lead to alteration of the natural history and prolongation of survival. Finally, combined use of these growth factors is another area warranting further investigations to achieve sustained improvement in either two- or three-cell lineages. PMID- 1613009 TI - Clinical course of myelodysplastic syndromes. AB - The myelodysplastic syndromes are a heterogeneous group of disease states ranging from relatively benign to aggressive forms. It is now possible to specify factors with prognostic value. Poor-prognosis factors that can easily be assessed are (1) bone marrow blasts exceeding 5% of the nucleated cells, (2) the presence of blast cells in the peripheral blood, (3) pancytopenia, and (4) a high Bournemouth, FAB, Dusseldorf, or Spanish score. Further important poor-prognosis features are (5) the presence of karyotypic abnormalities, (6) the finding of ALIP, and (7) a leukemic pattern of in vitro progenitor cell growth. The assessment of the value of therapeutic intervention either by treatment with hematopoietic growth factors or by chemotherapy will require the knowledge of the distribution of these features. PMID- 1613013 TI - Therapy-related myelodysplastic syndromes. AB - This article summarizes the clinical aspects, cytogenetics, and initiating agents associated with therapy-related myelodysplastic syndromes. Details regarding associated chemotherapeutic agents and ionizing radiation are discussed and therapeutic considerations are presented. PMID- 1613014 TI - Issues in the use of benzodiazepine therapy. AB - In selecting a hypnotic for the symptomatic management of insomnia, clinicians should look for those that most favorably balance sleep induction and sleep maintenance with potential adverse side effects. While all benzodiazepines have demonstrated efficacy in nocturnal sedation, the side effects of different compounds--and different doses of the same compound--vary greatly. The most common adverse effects associated with benzodiazepines are residual sedation, anterograde amnesia, and rebound insomnia, which are also related to the insomnia complaint itself. Therefore, careful evaluation of the dose of a benzodiazepine hypnotic is the key to effective treatment of insomnia without inducement of adverse effects. The most common side effects of hypnotics and their relation to drug dose are reviewed. PMID- 1613015 TI - Clinical uses and advantages of low doses of benzodiazepine hypnotics. AB - The most common adverse effects associated with the use of benzodiazepine hypnotics are residual daytime effects (daytime sedation and daytime performance decrements), anterograde amnesia, and rebound insomnia. Studies show that these adverse effects are related to dose. Hence, benzodiazepine hypnotics should be used in low doses so as to minimize or prevent these common adverse effects. It is now generally accepted that benzodiazepines should not be administered long term for the treatment of chronic "idiopathic" insomnia. Two noncontinuous sleep disturbances, insomnia in the elderly and transient insomnia in young and middle aged adults, are probably the most acceptable indications for the use of benzodiazepines. Low doses of short- and intermediate-acting benzodiazepines (triazolam and temazepam) are efficacious in the treatment of insomnia in the elderly, and preliminary evidence suggests that they are efficacious in the treatment of transient insomnia in young and middle-aged adults. PMID- 1613016 TI - Insomnia in the elderly. AB - Insomnia is common in the elderly population. Difficulty in initiating and maintaining sleep affects nearly half of all patients over the age of 65, representing an increased prevalence in older versus younger patients. Nocturnal sleep time is decreased, frequent awakenings occur, and daytime napping is common. Age-related changes in sleep physiology correlate with the subjective complaints of disturbed sleep. Multiple etiologies for insomnia in the elderly have been described. Management strategies must include attention to both nonpharmacologic and pharmacologic aspects of care, especially with respect to the altered pharmacokinetics and pharmacodynamics associated with advanced age. Reassessing therapy is essential to promote the end goal of improvement of the elderly patient's quality of life. PMID- 1613017 TI - Sleep disorders in the medically ill patient. AB - A careful medical evaluation is essential for any patient complaining of disturbed sleep so as to ascertain the contribution of possible metabolic, neurologic, or medication-related factors to symptom development. In this review, medical and neurologic conditions that may negatively affect sleep will be discussed as well as commonly offending medications. Special attention will be given to sleep apnea syndromes. The evaluation of sleep disturbance in the medical patient will be discussed with focus on of the special pharmacokinetic considerations involved in selecting medications for the treatment of disturbed sleep in this patient population. PMID- 1613018 TI - Nonpharmacologic treatments of insomnia. AB - Nonpharmacologic treatments that have been evaluated for insomnia are reviewed. These include sleep hygiene techniques, stimulus control instructions, sleep restriction, chronotherapy, bright light therapy, relaxation training, biofeedback, paradoxical intention, and cognitive therapy. Comparative studies of the different treatments indicate considerable overlap in effectiveness. Direct comparisons between treatments have shown stimulus control instructions to be more effective than either relaxation training or paradoxical intention. Further research is needed on the tailoring of treatments to patient needs, as are more detailed comparisons between pharmacologic and nonpharmacologic treatments. PMID- 1613019 TI - The epidemiology and occurrence of insomnia. AB - Although the definitions of insomnia have changed over the last decade to include the perceptions of patients and the effects of disturbed sleep on daytime function, no clear measure exists for isolating the scope of the problem within the general population. A 1979 Gallup poll survey showed that 95% of the adult population had experienced insomnia. The current literature maintains consistently that approximately one third of all people have sleep problems in any given year. Of those, only half consider the problem serious enough to seek medical advice. Sleep disorders appear to effect women more often than men, and the complaints increase with age. Younger people tend to have trouble falling asleep, while older people have difficulty maintaining sleep. The many varieties of sleep disorders and the diverse etiologies underlying them make it crucial that the individual sleep problem be understood clearly. An accurate diagnosis should drive treatment. PMID- 1613020 TI - A problem-solving approach to the treatment of insomnia: selected case histories. AB - The author presents case histories that demonstrate an approach to a spectrum of clinical scenarios that have common to them the complaint of insomnia. In the first, the physician is faced with an acute problem with an easily apparent, but superficial, etiology. The use of a benzodiazepine in this instance would be relatively noncontroversial. Its usage, without an exploration of the patient's perceptual frame, including psychosocial factors, would miss potentially important underlying problems. In the second case, the physician's concern about the habituating effects of benzodiazepines could have resulted in the underutilization of their benefits. The third case represents a scenario in which overutilization with resultant habituation was potentially a problem. It becomes apparent that an "either/or" generalization might hinder good patient outcome. Questioning around the symptom for purposes of gathering information regarding the patient's perceptual frame and the consequences of change may be useful in developing treatment strategies. PMID- 1613021 TI - Variations between Biomer lots. I. Significant differences in the surface chemistry of two lots of a commercial poly(ether urethane). AB - We have studied the surface chemistry of two lots of Biomer (BSP067 and BSUA001), a widely used commercial poly(ether urethane) (PEU). Although transmission infrared adsorption studies revealed no differences in the bulk chemistry of the two lots, the surface chemistry, as seen by x-ray photoelectron spectroscopy (XPS) and static secondary ion mass spectrometry (SIMS), was different. Lot BSP067 showed soft-segment enrichment at the surface, which is typical of PEU. Lot BSUA001 showed no evidence of either hard- or soft-segment PEU components at the surface. The surface of this lot was completely covered with a nonextractable additive identified as poly(diisopropyl amino ethyl methacrylate). Small amounts of a low-molecular-weight antioxidant were observed at the surface of both samples. Because the biological response to polymers is dependent on surface structure, these results are of considerable importance to biomaterials research. PMID- 1613022 TI - Formation of focal contacts by osteoblasts cultured on orthopedic biomaterials. AB - The nature of the contact sites formed during the adhesion of osteoblasts to orthopedic implant materials was investigated by fluorescence microscopy. More specifically, the cytoskeletal organization of and the focal contact formation by neonatal rat calvarial osteoblasts attaching to and spreading on 316L stainless steel, Ti-6Al-4V, Co-Cr-Mo, Synamel (hydroxyapatite), alumina, and borosilicate glass were examined. Focal contacts are regions where the plasma membrane approaches the substrate to within 10-15 nm and where bundles of cytoskeletal microfilaments terminate. Fluorescent-labeling of F-actin-containing microfilaments demonstrated a typical sequence of events as rounded, suspended osteoblasts spread onto the substrates. Immunofluorescent-labeling of the protein vinculin, which is found at the cytoplasmic face of focal contacts, initially showed the formation of streak-like focal patches. On the biomaterials, the vinculin staining subsequently extended up and along, but ventral to, the microfilament bundles. The fibrillar patterns observed at later times may evidence the formation of extracellular matrix contacts. PMID- 1613023 TI - Hyaluronan solution as a cartilage antidesiccant. AB - During arthrotomy, desiccation of the articular cartilage of synovial joints by the ambient environment of the operating room causes chondrocyte death and may promote degenerative changes within the joint. This study documents the efficacy of a biomaterial, hyaluronan (HY) solution, to maintain chondrocyte viability during desiccation. Rabbit patellar articular cartilage was air-dried for 2 h with and without application of the HY solution. As assessed by 35SO4 uptake and autoradiography, the HY solution helped maintain chondrocyte viability, when compared to air dried specimens (p less than or equal to 0.02). HY solution applied to the articular surfaces of joints undergoing arthrotomy may offset the detrimental effects of desiccation, such as chondrocyte death and degenerative joint changes. PMID- 1613024 TI - The mechanisms of passive dissolution of titanium in a model physiological environment. AB - The surface chemistry, oxidation, and disolution kinetics of titanium were measured to establish the mechanisms of passive dissolution in physiological environments. Titanium thin films were immersed in 8.0 mM ethylenediamine tetraacetic acid in simulated interstitial electrolyte (EDTA/SIE) and maintained at 37 degrees C, 10% O2, 5% CO2 and 7.2 pH for periods of time up to 3200 h (133 days). Two immersion schemes were employed: the integral sequentially determined the titanium released into a solution of accumulated dissolution products; and the differential continuously replenished the test solution. The solutions were analyzed for titanium by electrothermal atomic absorption spectrometry (EAAS), and the sample surfaces were analyzed by Auger electron spectroscopy (AES) and x ray photoelectron spectroscopy (XPS) to determine oxide composition, stoichiometry, and thickness. Prior to immersion two types of hydroxyl (OH) groups were distinguished on the TiO2 surface. Upon immersion, the chemistry of the surface changed as a function of immersion: the presence of OH groups increased and P (nonelemental) was detected at the surface. The dissolution kinetics obeyed a two-phase logarithmic model, where the transition between phases occurred simultaneously with the adsorption of the P-containing species. The dissolution kinetics depended on surface reactions, electric field strength, and molecular diffusion. These mechanisms explain the observed dependence of dissolution kinetics on the properties of the surface oxide and solution ligands. PMID- 1613025 TI - Comparative studies by cell culture and in vivo implantation test on the toxicity of natural rubber latex materials. AB - Colony assay using V79 cells, the agar diffusion assay with L929 cells, and the 7 day rabbit muscle implantation test were employed to evaluate the cytotoxicity and tissue toxicity of natural rubber latex (NRL) materials. The in vivo implantation test showed that, among 13 histological parameters, thickness of inflammatory layer was the most useful index to evaluate tissue responses quantitatively. A comparison of the in vivo and in vitro parameters revealed the following correlations between the thickness of the inflammatory layer and cytotoxicity indices: Colony assay of the extracts, IC50: r = 0.80; Agar diffusion assay, Zone index: r = 0.73; Lysis index: r = 0.61. From these results, it appears that the colony assay provides a more reliable prediction of the tissue response than the agar diffusion assay. PMID- 1613026 TI - Ex vivo and in vitro platelet adhesion on RFGD deposited polymers. AB - Clinical applications of small-diameter synthetic vascular grafts are hindered by their highly thrombogenic surfaces. To develop vascular grafts that resist thrombotic occlusion, a radio frequency glow discharge (RFGD) process was employed to modify the surface of existing graft materials. Ultrathin coatings of RFGD polymers of ethylene (E), tetrafluoroethylene (TFE), and hexamethyldisiloxane (HMDS) were deposited on the lumen of Dacron grafts. Surfaces were characterized by electron spectroscopy for chemical analysis (ESCA). The effect of glow discharge treatments on platelet-graft interactions was evaluated in an ex vivo baboon shunt model. Following placement of an untreated or RFGD-treated graft in the shunt, deposition of 111Indium-labeled platelets was monitored for 60 min by gamma camera imaging. Untreated Dacron rapidly accumulated large numbers of platelets, reaching a plateau in 60 min. HMDS- and TFE-treated Dacron had significantly lower levels of platelet deposition compared to the untreated control. In contrast, the ethylene treatment of Dacron augmented platelet deposition, making it the most platelet-adherent surface studied. In vitro studies were also performed using untreated and RFGD treated poly (ethylene terephthalate) (PET) coverslips. ESCA verified that the surface composition of the untreated and RFGD-treated coverslips were virtually identical to their untreated and treated Dacron graft counterparts. Samples were incubated in washed baboon platelet suspensions for 2 h at 37 degrees C. Platelet adhesion on the untreated PET was relatively high, and many of the platelets had a completely spread morphology. The HMDS and TFE treatment of PET reduced the number of adherent platelets and prevented platelet spreading on the surface. Platelet adhesion and spreading on the ethylene-treated surface was the highest among the four studied. There is a remarkable linear correlation of the ex vivo and in vitro platelet adhesion data. PMID- 1613027 TI - Synthesis of photoreactive poly(ethylene glycol) and its application to the prevention of surface-induced platelet activation. AB - Photoreactive poly(ethylene glycol) (PEG) was synthesized by reacting 4-fluoro-3 nitrophenyl azide (FNPA) with sodium salt of PEG. The synthesized 4-azido-2 nitrophenyl PEG (ANP-PEG) was characterized by 1H-NMR, IR, and UV spectroscopy. ANP-PEG was grafted to dimethyldichlorosilane-coated glass (DDS-glass) by photolysis without any premodification of the surface. The effects of various grafting factors, such as the polymer adsorption time, concentration of ANP-PEG, and UV irradiation time, on the PEG grafting efficiency were examined. The PEG grafted DDS-glass was characterized by measuring surface free energies, surface induced platelet activation, and the relative amount of PEG grafted on the surface using electron spectroscopy for chemical analysis (ESCA). Platelet adhesion and activation was analyzed by measuring the number and spread area of adherent platelets. The results showed that ANP-PEG had to be adsorbed onto DDS glass for at least 12 h before photolysis for the maximum grafting efficiency. No platelets could adhere to the PEG-grafted DDS-glass, if the bulk concentration of ANP-PEG in the adsorption solution was between 1 mg/mL and 10 mg/mL. Above 10 mg/mL, platelet activation gradually increased and reached the maximum at 30 mg/mL. Our data indicate that the grafting of ANP-PEG requires careful control of the grafting conditions and that the grafted PEG can prevent surface-induced platelet activation. PMID- 1613028 TI - Cell adhesion and growth on synthetic elastomeric matrices containing Arg-Gly-Asp Ser-3. AB - Synthetic elastomeric polypeptide matrices based on the repeating amino acid sequences of elastin have biophysical and biological properties which are favorable for prosthetic materials. An important requirement envisaged for some applications is the ability to support cell adhesion and growth. The X20-poly (GVGVP), the gamma-irradiation cross-linked elastomeric matrix based on the repeating pentamer Val-Pro-Gly-Val-Gly, and X20-poly[n(GVGVP), (GRGDSP)] containing the covalently incorporated cell adhesion sequence Arg-Gly-Asp-Ser (RGDS) were synthesized. These matrices were tested for their ability to support the adhesion and growth of bovine aortic endothelial cells and of bovine ligamentum nuchae fibroblasts. Adhesion experiments carried out in albumin containing media showed that matrices containing 60:1, 40:1, and 20:1 ratios of (GVGVP):(GRGDSP) supported maximal cell attachment, that matrices containing 100:1 exhibited an intermediate level of attachment and that matrices composed of 500:1 and (GVGVP) alone were very poor supports for cell attachment. Serum in the media promoted submaximal cell attachment to X20-poly(GVGVP) but did not permit substantial cell growth. Cell growth was supported by matrices having high ratios of (GRGDSP). Ratios of 60:1, 40:1, and 20:1 supported three population doublings of endothelial cells over 3 days resulting in confluent matrix-adherent monolayers. Ratios of 40:1 and 20:1 similarly supported the growth of fibroblasts. PMID- 1613030 TI - Nerve compression syndromes. PMID- 1613029 TI - Peripheral nerve anatomy and innervation pattern. AB - This article discusses three basic parts of peripheral nerves. A description of the nerve fiber includes sections on both myelinated and unmyelinated axons. The anatomy of the peripheral nerve at the cellular level is reviewed encompassing the nerve, the surrounding connective tissue framework, and the supportive vascular supply. Finally, normal and abnormal innervation patterns of the hand and forearm are presented. Anastomosis and variations of the normal anatomy are discussed. PMID- 1613031 TI - The pathophysiology of nerve compression. AB - The basic pathophysiology of an acute and chronic nerve compression lesion is complex. Compression of a peripheral nerve induces marked changes in intraneural microcirculation and nerve fiber structure, impairment of axonal transport, and alterations in vascular permeability, with edema formation and deterioration of nerve function. The peripheral nerves of subjects with underlying neuropathies are more susceptible to compression injury. PMID- 1613032 TI - Patient evaluation and management considerations in nerve compression. AB - This article details the history, physical examination, and differential diagnosis for patients with nerve compressions. Multiple crush syndrome and diabetic neuropathy are specifically discussed. General management considerations are presented. PMID- 1613033 TI - Electrodiagnosis of compressive nerve lesions. AB - Electrodiagnostic studies provide valuable information that can be a useful adjunct to careful clinical evaluation in the diagnosis of compression neuropathy. Such studies can also help to predict the outcome of treatment and differentiate nerve injuries amenable to successful surgical intervention. PMID- 1613034 TI - Neuropathy in the workplace. AB - Cumulative trauma disorders are frequently responsible for the development of occupational neuropathy. Predisposing factors in the workplace are identified, and ergonomic principles to minimize these risks are presented. PMID- 1613035 TI - Compressive neuropathies in the upper extremity of athletes. AB - The physician responsible for the evaluation and treatment of athletes must include nerve compression injury in the differential diagnosis of upper extremity pain and dysfunction. Careful history and physical examination, along with selective objective testing, should be diagnostic. Treatment and prevention methods implemented under the supervision of knowledgeable trainers and coaches may allow for complete resolution of symptoms and, more importantly, prevent recurrence. Adolescents and novice athletes in many sports may be at the highest risk for this type of overuse injury. PMID- 1613036 TI - Thoracic outlet syndromes. AB - TOS may arise in a variety of circumstances including trauma, but it may also be seen as a result of postural abnormalities that may be induced by different factors. Cervical ribs and other congenital anomalies are not necessary prerequisites for either the causation or diagnosis of TOS, although they are more common in the TOS population. More important than diagnostic tests are the history and physical examination of the patient. Double crush syndrome can complicate the diagnosis and treatment; however, proper selection of candidates for surgery can produce excellent and good results in a high percentage of cases. Perioperative complications can be significant, so that surgery should be restricted to only those patients who find their symptoms intolerable. PMID- 1613037 TI - Nerve entrapment about the shoulder girdle. AB - Nerve entrapments about the shoulder can cause severe pain and can be disabling. A precise diagnosis must be established based on a thorough history and physical examination, and laboratory tests (EMG for example) are necessary. Definitive treatment with decompression or release of the affected nerve often relieves shoulder pain. PMID- 1613038 TI - Proximal median nerve compression. AB - Compression neuropathies of the median nerve in the proximal forearm are unusual lesions. Many patients have vague symptoms for many months or even years prior to confirming the diagnosis of either pronator syndrome or anterior interosseous syndrome of the forearm. Serial examinations clinically and electrodiagnostically may be necessary at intervals of 6 to 8 weeks as required for the evaluation of the patient's symptoms. As with other compression neuropathies, the diagnosis is solely dependent on the diagnosis of neuropathy of the median nerve using whatever parameter satisfies the surgeon's diagnostic criteria and then having made that diagnosis, localizing the site of that neuropathy by physical examination or electrodiagnosis with the support of radiographic techniques as appropriate. Surgical exploration of proximal median nerve compression is normally followed by prompt and predictable recovery from the median neuropathy and clinical symptoms between 8 and 12 weeks after surgical exploration. Prolonged symptom complexes after surgical exploration of the proximal median nerve are, in my experience, due to either (1) extremely severe median nerve injury secondary to pronator syndrome with prolonged recovery and distal nerve axomnetic recovery into the hand, or (2) sensory nerve dysesthesis of the small sensory nerves on the proximal volar surface of the forearm. The symptoms of either of these postoperative findings normally improve with time. PMID- 1613039 TI - Median nerve compression at the wrist. AB - Median nerve decompression at the wrist is one of the most common operative procedures performed by hand surgeons, yet studies report surgical failure rates of 7% to 20%. Symptoms must be coordinated with diagnostic studies. Initial paresthesias should be documented with delayed sensory conduction time. Threshold tests of sensibility, such as the Semmes-Weinstein monofilaments, are more consistent and reliable tests of decreased sensibility than innervation density tests, such as the Weber two-point discrimination test. Thenar atrophy should be documented with electromyographic studies. The median nerve should be evaluated from the fingertips to the cervical spine. Basic laboratory studies should test for collagen disease, thyroid or renal disorders, and diabetes mellitus. Appropriate roentgenograms must be obtained. Patients with normal laboratory and diagnostic studies should be offered nonoperative treatment. Factors that are important in predicting the patient's response to nonoperative treatment include: age over 50 years, constant paresthesias, intermittent paresthesias of more than 10 months duration, stenosing flexor tenosynovitis, and a wrist flexion test (Phalen) that is positive in less than 30 seconds. Fewer than 10% of patients with three or more of these factors present have been cured by nonoperative management. Surgical decompression of the carpal tunnel is done with tourniquet control and optical magnification. A longitudinal "zig-zag" incision is preferred that extends along the thenar crease, then proceeds ulnarly to reach the distal palmar crease at a point in line with the long axis of the ring finger, and then proceeds radially to the tendon of the palmaris longus. After release of the transverse carpal ligament, the motor branch should be explored and decompressed.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613040 TI - Proximal ulnar nerve compression. Cubital tunnel syndrome. AB - Ulnar nerve compression about the elbow is common. If diagnosed and treated early, satisfactory results can be expected. Severe chronic nerve compression may lead to permanent nerve damage. The diagnosis can be made by careful history, physical examination, knowledge of the nerve anatomy, and sometimes electrodiagnosis. Cubital tunnel syndrome must be differentiated from TOS and ulnar tunnel syndrome. Double-crush syndrome should be ruled out. Nonoperative treatment must be attempted first, whereas surgical treatment is indicated in severe and chronic cases. Satisfactory results can be achieved after surgery if nerve damage is absent and careful attention to technical details and gentle handling of the nerve are exercised. PMID- 1613042 TI - Radial nerve compression. AB - Symptomatic radial nerve compression is relatively uncommon. A relatively high incidence of compressive neuropathy involves other major nerves in the same extremity. Because sensory complaints are minor, radial nerve compression may successfully masquerade as tendonitis or tendon rupture. The most common site of radial nerve compression is in the forearm, at the arcade of Frohse. Spontaneous onset of dense paralysis is often due to space-occupying lesions in the forearm. Trauma-related compression in the forearm is most often due to radial head dislocation and either humeral fracture or local external pressure in the upper arm. Compression resulting in weakness that does not improve with several months of splinting, anti-inflammatory medication, and activity changes should be treated surgically to reduce the extent of permanent deficit. After decompression, early active motion is instituted to encourage nerve gliding. Results after decompression are not as favorable as those for carpal or cubital tunnel release. The worst results of decompression are seen in patients who have work-related injuries, chronic pain, and poor localization of symptoms on physical examination. PMID- 1613041 TI - Ulnar nerve compression at the wrist. Ulnar tunnel syndrome. AB - Compression neuropathy of the ulnar nerve at the wrist can be caused by several lesions. The most common cause is a carpal ganglion followed by occupational repeated trauma to the hypothenar area. This process is in contrast to carpal tunnel syndrome in which the majority of the cases are idiopathic in nature with no local cause found except for synovitis of the flexor tendons. The site of the lesion will determine the clinical picture whether it is both motor and sensory abnormalities, only motor paralysis or only sensory abnormality. The latter is rare. If the abnormality is purely motor, then the compression is distal in the ulnar tunnel and the hypothenar muscles are usually spared. Carpal ganglia must be sought and removed. After an extensive search through the literature, I found only one report in which thickening of the volar carpal ligament was found to be the cause of ulnar nerve compression. I encourage the use of the term "ulnar tunnel syndrome" to discuss these lesions and the classification outlined by Shea to determine the site of the lesion. Patients with type 2 syndrome usually present late because of the lack of sensory changes. Average delay in obtaining a diagnosis of 5 months was found in my patients. The condition should be suspected if spontaneous clumsiness or awkwardness of the use of the hand occurs in a middle-aged patient. PMID- 1613043 TI - Digital nerve compression. AB - A review of the relatively small body of literature about digital nerve compression injuries has been supplemented by the author's experience and interest of over 40 years. The principal lesions involved are of two types: (1) fibrosis about, around, and in the nerve; and (2) reactive hyperplasia of the nerve support elements and sometimes of special end organs, Pacinian corpuscles, and even of the nerve fibers themselves. Nerve signs and symptoms often accompanied by a mass in chronic cases are diagnostic. The most important features of the topic are the recognition by all of the risk elements, embodied in many personal and professional devices and techniques. These risk elements are present in all parts of our society, including home and occupational, avocational, and medical situations. Treatment is best provided by awareness of risk and avoidance of risk activities, particularly repetitive risk activities. Surgery is preferably avoided, but when indicated it is effective. It consists principally of lysis and protective positioning of the damaged nerve or, on occasion, of excision of terminal or end-organ lesions. More information must be gathered about these exceedingly common but notably under-reported problems. PMID- 1613044 TI - Double and multiple "crush" syndromes. Double and multiple entrapment neuropathies. AB - The double crush hypothesis suggests that serial constraints to axoplasmic flow, each of which is insufficient to cause changes in function by itself, can be additive in causing ultimate dysfunction of the nerve. Careful clinical examination will be required to localize the significant levels of nerve compression. Frequently, patients will be asymptomatic in the nonprovoked position. A comparison of neurological testing "at rest" and then subsequent to provocation of the patient's symptoms may be the only mechanism by which the surgeon will be able to quantity an abnormality that corresponds to the patient's symptoms. Surgical intervention, especially when the etiologic factor is work related, is always postponed until maximum job modification has been carried out. Surgical management of these patients without a significant change in the patient's work habits that provoked the compression neuropathies in the first instance will frequently be associated with a recurrence of symptoms when the work is resumed. PMID- 1613045 TI - Surface-modified membranes as a matrix for protein purification. AB - Recently introduced membrane-based chromatographic supports for protein separation are available either with a coupled ligand, e.g., protein A, protein G or ion-exchange groups, or as activated matrices for coupling a desired ligand. The coupling conditions for protein A and immunoglobulin G to an epoxy-activated membrane were determined. The performance of the prepared affinity membranes was investigated using pure rabbit immunoglobulin G and protein A as a model system. For practical application monoclonal antibodies from cell culture supernatant were purified with a prepared protein A membrane and for comparison with a sulphonic acid ion exchange membrane. PMID- 1613046 TI - Diffusion of proteins in Sepharose Cl-B gels. AB - The reduced diffusion coefficient, D/D0, of fluorescein-labelled globular proteins in the agarose gels Sepharose Cl-2B, 4B and 6B were measured by the FRAP method. Comparison of the partition coefficients of the native and the labelled proteins in the gel showed that the fluorescein residues did not introduce new interactions between the solute and the gel matrix. D/D0 decreased as a function of the Stokes radius. The variation of D/D0 as a function of the partition coefficient of the proteins in the gel did not agree with a previously published prediction. This is in contrast with the diffusion of globular proteins in ACA34 gel, in which the sieving matrix is made of cross-linked polyacrylamide. PMID- 1613047 TI - Analysis of pH-dependent protein interactions with gel filtration medium. AB - A prepacked Superose 12 HR 10/30 column was used to study the effects of elution ionic strength and pH on the chromatographic behaviour of a strong hydrophobic Clostridium thermocellum endoglucanase (1) and two weak hydrophobic proteins, Clostridium thermocellum endoglucanase C and egg white lysozyme. Ion-exclusion or ion-exchange interactions between weakly hydrophobic proteins and the gel matrix were observed at low ionic strength, depending on whether the pH of the elution buffer was higher or lower than the pI values of the proteins. These interactions were due to the presence of negatively charged groups on the surface of Superose and could be eliminated at any pH by adding electrolyte at a concentration determined by its chemical identity. The optimum results were observed with sodium sulphate at a concentration of 100 mM. The chromatographic behaviour of strong hydrophobic endoglucanase (1) on a Superose column as a function of pH was much more complex because of two interplaying effects, electrostatic and hydrophobic. Ideal size-exclusion chromatography could be achieved only in a narrow range of the conditions: first, the mobile phase must contain a weak salting-out electrolyte such as NaCl, and second, the mobile phase pH must be high enough that hydrophobic interactions between the solute and support are balanced by their electrostatic repulsion. At pH greater than pI, the retardation of endoglucanase (1) gradually increased with decreasing pH as a result of lowering of repulsive electrostatic interactions whether or not the buffer ionic strength was high. At pH less than pI a drastic increase in the capacity factor k' was observed owing to the additivity of hydrophobic and ion-exchange effects.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613049 TI - Determination of organic acids, amino acids and saccharides by high-performance liquid chromatography and a postcolumn enzyme reactor with amperometric detection. AB - A technique for the determination of organic acids, amino acids and sugars is described. The compounds of interest are separated by high-performance liquid chromatography (HPLC) and converted on-line by immobilized enzymes. The enzymes employed are covalently bound to a synthetic carrier. Hydrogen peroxide, which is produced in the reaction with oxidases, makes possible the application of an electrochemical detector. This arrangement combines the separation efficiency of HPLC, the substrate specificity of enzymes and the high sensitivity of electrochemical detection. The enzymes act according to known reaction mechanisms, but coupling with HPLC leads to a promising extension in the field of biosensors. The simple pretreatment of the samples (often a dilution step is sufficient) allows a rapid analysis of foodstuffs and biological or clinical extracts. The examples presented demonstrate the very high sensitivity of the method with detection limits in the nano- to picomolar range and a wide field of application. PMID- 1613048 TI - Interfacing gradient elution ion-exchange chromatography and low-angle laser light-scattering photometry for analysis of proteins. AB - Molecular weights (MWs) of different proteins were determined by interfacing gradient elution ion-exchange chromatography and low-angle laser light-scattering photometry (IEC-LALLS). A high-performance strong cation-exchange column was used to elute proteins using fast (5 min) and conventional (15-30 min) gradients. The eluted proteins were characterized on-line by determining their MWs using LALLS. The specific refractive index (RI) increment (dn/dc) and the RI of the solvent used over the gradient range were determined off-line and used to calculate the absolute weight-average MWs. Four proteins, ribonuclease A, alpha chymotrypsinogen A, trypsinogen and beta-lactoglobulin A (beta-LACT) were studied. Accurate MWs were obtained for all the proteins using fast and conventional gradients, except for beta-LACT, which aggregated as a function of the gradient employed. The degree of aggregation of beta-LACT increased as the rapidity of the gradient was increased over a fixed gradient range. This study indicated that it is possible to separate and characterize proteins rapidly using IEC-LALLS. PMID- 1613050 TI - Improvement of extraction procedure for biogenic amines in foods and their high performance liquid chromatographic determination. AB - A high-performance liquid chromatography method is described for the simultaneous determination of the biogenic amines tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, and spermine in cheese. The optimization of the procedure for the extraction of amines from the matrix is described. The separation of dansyl derivatives of the amines was achieved by reversed-phase liquid chromatography with gradient elution, followed by UV detection at 254 nm. The mobile phase was acetonitrile-0.01 M phosphate buffer (pH 7)-water. Under these conditions, rapid elution of the amines in less than 13 min was obtained. Validation of the method included calibration experiments, addition of standard amines for the determination of amine recoveries and repeatability tests. PMID- 1613051 TI - Amino acid analysis by high-performance liquid chromatography after derivatization with diethyl ethoxymethylenemalonate. AB - Amino acids were determined by precolumn derivatization with diethyl ethoxymethylenemalonate and reversed-phase high-performance liquid chromatography (HPLC) with spectrophotometric detection at 280 nm. The reaction time was 50 min and the derivatives were stable at room temperature. Chromatographic resolution of a mixture of the derivatives of seventeen amino acids, including proline and cystine, was achieved within 35 min using a binary gradient system. The detection limit was 3 pmol. Amino acid analyses of acid hydrolysates of two proteins gave results equivalent to those obtained by conventional ion-exchange-based amino acid analysis. The simplicity of the procedure allows its use on any multi purpose HPLC system. PMID- 1613052 TI - Rapid isolation of human complement component C9 to verify the specificity of a haemolytic C9 microassay. AB - A sensitive, haemolytic microassay of human complement component C9 was developed. The assay is based on the principle of reactive (C5b6-initiated) haemolysis and uses commercially available C9-depleted serum as reagent for C9. The specificity of the assay was verified by rapid, activity-guided isolation of the haemolytic component from human serum using high-performance liquid chromatography (HPLC) on a system for fast protein liquid chromatography. This isolation yielded a single component with characteristics of C9. The results suggest that rapid, activity-guided isolation as a new application of HPLC can be a useful tool to demonstrate the specificity of a functional assay. PMID- 1613053 TI - Determination of aminoglycoside antibiotics by reversed-phase ion-pair high performance liquid chromatography coupled with pulsed amperometry and ion spray mass spectrometry. AB - This work constitutes a preliminary investigation of a high-performance liquid chromatographic (HPLC)-mass spectrometric (MS) method for confirming aminoglycoside residues in bovine tissues. A reversed-phase ion-pair HPLC method for the separation of four aminoglycosides was developed using volatile ion pairing agents and optimized for detection with an ion spray HPLC-MS interface. The method is also compatible with a commercial pulsed amperometric detector that was used for HPLC method development and that may be useful for the screening and quantification phases of a regulatory method. Several column phases, eluent compositions, and pairing ions were evaluated for optimum HPLC-MS sensitivity. Detection limits are in the low nanogram range with the pulsed amperometric detector and with HPLC-MS in the selected ion monitoring mode. Results with bovine kidney, fortified to 20 ppm and extracted by matrix solid-phase dispersion, obtained using both detectors are presented. PMID- 1613054 TI - Optimization of a peak compression system for a remoxipride metabolite (FLA797) and its application to bioanalysis. AB - A peak compression system is optimized for FLA797 (I), a phenolic tertiary amine and a metabolite to the antipsychotic drug remoxipride. An application is described where this effect is used to give a 6-7-fold improvement of the quantification limit in an assay of I in plasma. The liquid chromatographic system is constructed so that the injection of I dissolved in a solution of a competing amine gives a very high and narrow analyte peak with an apparent efficiency of 1.5 x 10(6) plates/m. When the levels of I in plasma are determined, an internal standard, giving a normal isocratic peak, is added to the plasma sample before the extraction. Concentrations of I down to 0.5-1.0 nM can be determined with reasonable precision. FLA908, another phenolic remoxipride metabolite and a regioisomer to I, eluting as a normal isocratic peak, can be determined simultaneously although only at concentrations higher than 10-15 nM. PMID- 1613055 TI - High-performance liquid chromatographic-mass spectrometric analysis of oligosaccharides from enzymatic digestion of glycosaminoglycans. Application to human samples. AB - Glycosaminoglycan contents were evaluated in plasma and urine samples from volunteers treated intravenously with a mixture of dermatan sulphate and heparin, combining a novel liquid chromatographic-mass spectrometric technique for the determination of oligosaccharides from glycosaminoglycans with a classical technique for the extraction of glycosaminoglycans from biological samples (precipitation with cetylpyridinium chloride). In plasma samples dermatan sulphate and heparin can be measured for 2 h after treatment; urine excretion was detectable for 24 h. These results suggest that this novel approach is promising for future studies on the pharmacokinetics of glycosaminoglycans, although some technical aspects need further improvement, mainly regarding the procedures for sample clean-up; cetylpiridinium precipitation is a complex procedure and the recovery is limited. PMID- 1613056 TI - Comparative study of clean-up and fractionation methods for the determination of organochlorine pesticides in lipids by gas chromatography. AB - Three of the methods most often used for the clean-up and fractionation of organochlorine pesticides in lipid residue analysis by gas chromatography with electron-capture detection were compared. The overall recoveries of twenty pesticides from spiked samples were higher than 88%, the relative standard deviation being in the range 3-11% (n = 6) at the 36-80 ppb (10(9) level. The three methods were compared by analysis of variance, with no differences in precision at the 0.05 significance level. Differences in recoveries appeared in only two instances. None of the three methods seems to be significantly better than the others for the determination of the pesticides studied. PMID- 1613057 TI - Comparison of liquid-junction and coaxial interfaces for capillary electrophoresis-mass spectrometry with application to compounds of concern to the aquaculture industry. AB - The application of capillary electrophoresis-mass spectrometry (CE-MS) to the analysis of compounds of concern to the aquaculture industry is reported. Two different approaches to coupling the CE column to an IonSpray atmospheric pressure ionization (API) interface, viz., a liquid-junction and a coaxial arrangement, are describe and compared with regard to ruggedness, ease of use, sensitivity and electrophoretic performance. The different injection modes used in three commercial capillary electrophoresis systems were also evaluated for their applicability to CE-MS. The use of CE-MS for the analysis of a variety of classes of antibiotics used in the fish aquaculture industry, such as the sulfonamides and their potentiators (e.g., trimethoprim), is demonstrated and was used to confirm the presence of these components in shellfish extracts at the low ppm level. CE-MS was also applied to the analysis of marine toxins such as saxitoxin and its analogues which are associated with paralytic shellfish poisoning, and also the toxins responsible for amnesic and diarrheic shellfish poisoning. Tandem mass spectrometry (MS-MS) was used to provide structural information on these analytes, and the ability to distinguish isomeric compounds based on their different migration and fragmentation characteristics using CE-MS MS is demonstrated. PMID- 1613058 TI - Photoionization assessment of C3-C5 alkadienes and alkenes in urban air. AB - Hydrocarbons from samples of traffic-polluted urban air were separated by gas chromatography on an aluminium oxide column and assessed simultaneously by photoionization detection (PID) and flame ionization detection (FID) after effluent splitting. The 10.2 eV photoionization detector selectively detects alkadienes and alkenes but not alkanes and alkynes in the C3-C5 region. The maximum PID/FID response ratio for alkadienes and alkenes is also obtained in this region. The analytical system as a whole is particularly favourable for the C3-C5 alkenes. Analytical data are given for propadiene, 1,3-butadiene, propene, butenes and pentenes. PMID- 1613059 TI - RM values of some colchicines and colchiceinamides determined by reversed-phase thin-layer chromatography. AB - The RM values of twelve colchicines and eight colchiceinamides were measured using reversed-phase thin-layer chromatography. The RM values were calculated by extrapolation from the linear range of a plot of RM values versus the composition of the mobile phase. The results showed that in the colchicine series substitution at the nitrogen in position C7 decreases the lipophilicity, whereas in the colchiceinamide series substitution at the nitrogen in position C10 increases lipophilicity. The influence of other substituent groups on the RM values are considered. PMID- 1613060 TI - Retention processes on alpha 1-acid glycoprotein-bonded stationary phase. AB - Stereoselective separations of charged enantiomers on CHIRAL-AGP can be controlled by varying the pH and adding charged and uncharged additives to the mobile phase. The interaction with the selector, alpha 1-acid glycoprotein, was studied by monitoring the effects of the variables on retention and by indirect detection, in part using a simple multivariate design. The stereoselectivity is due to simultaneous retention processes involving ion-exchange and ion-pairing mechanisms. The predominant mode of interaction for different solutes was elucidated from variables that promote or counteract either of the processes. Considerable improvements in the stereoselectivity were achieved with chiral or achiral anionic and cationic additives that act in a synergistic or competitive mode. PMID- 1613061 TI - Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases. IX. Influence of the cross-linking reagent on the retentive and enantioselective properties of chiral sorbents based on bovine serum albumin. AB - Three modifications of silica-bound, cross-linked bovine serum albumin (BSA) were evaluated as chiral sorbents for use in the liquid chromatographic separation of enantiomers. Glutaraldehyde, formaldehyde and di-(N-succinimidyl) carbonate were used as bifunctional reagents for the immobilization of BSA. The sorbents all contain the same loading of BSA (14.4 +/- 0.1%, w/w) and differ only with respect to the cross-linker used for immobilization. Despite their apparent similarity, the sorbents show very different chromatographic properties, not only with respect to retention of analyte enantiomers (k' and alpha), but also with respect to column efficiency (affecting Rs values). The data obtained indicate that the chemical structure of the cross-linking reagent affects to a large extent the accessibility of important chiral binding sites. Although the data obtained are difficult to interpret in any detail, certain generalizations concerning the different behaviour of the sorbents can be made. PMID- 1613062 TI - Oriented immobilization of peptide ligands on solid supports. AB - A synthetic procedure was developed for the direct immobilization on preactivated affinity supports of peptidic ligands requiring free alpha-amino groups to recognize their targets properly. The peptidic ligand is assembled by solid-phase peptide synthesis on an octa-branched heptalysine core through a polyglycine spacer, similar to the method developed for the production of multiple antigenic peptides. After deblocking from the resin, peptide is dialysed, lyophylized and used directly for coupling to preactivated supports. Following immobilization, only a limited number of peptide chains are covalently linked to the solid phase, leaving the remainder facing the mobile phase and sufficiently spaced to interact properly. This procedure was applied successfully to the design, synthesis and oriented immobilization of a multimeric tripeptide ligand (Met-Tyr-Phe) for affinity purification of bovine neurophysin. PMID- 1613063 TI - [Infant acute leukemia]. PMID- 1613064 TI - [Factors affecting regularity of counseling and/or medication in schizophrenics in an outpatient setting]. AB - The author investigated a number of factors which affect regularity of counseling and/or medication in schizophrenics in an out-patient setting. A hundred and forty eight schizophrenic out-patients at a psychiatric hospital in Yamagata were examined over a period of three years. The factors consisted of age, sex, family setting, profession, place of residence, financial status, utilization of the aftercare system, insight about their illness and attitude towards drug therapy. Most of the patients maintained good levels in the regularity of counseling and/or medication and their attitude towards therapy was unchanged throughout the course. On the other hand, there is a statistically significant difference between the regularity of counseling and/or medication one month before readmission and at other times. Good levels in regularity is associated with such factors as being male, being single, working conditions, financial status, insight about their illness, positive attitude towards drug therapy and utilization of aftercare system. We had great difficulty in improving the regularity of counseling and/or medication among those schizophrenic patients. But intensive intervention such as enrolling in a day care system could have a favourable effect on the regularity of counseling and/or medication. It may be of benefit in the future to promote further development of such support systems. PMID- 1613065 TI - [A comparative study of histopathological findings and CT images related to pancreatic carcinomas. An attempt at diagnosis in tissue characterization by CT]. AB - From January 1980 to February 1991, computed tomography (CT) images of 39 patients with pancreatic carcinoma who had undergone surgery at the National Cancer Center Hospital were reviewed retrospectively. The average age of the patients was 63.0 years (the range was from 45 to 78), with 19 males and 20 females. The histopathological diagnosis was tubular adenocarcinoma in 35 cases, papillary adenocarcinoma in 2 and other diagnoses in 2. The tumor was located at the head of the pancreas in 25 cases and at the body and/or tail in 12. In the remaining 2 cases, the tumor was at the head and body in one, and at the whole pancreas in the other. The CT images were compared with the histopathological findings, and four parameters were determined to establish the histological characterization of pancreatic carcinomas in CT: density (plain CT, CE-CT) characteristics, margin of the tumor, and delayed contrast enhancement. CT findings such as irregular margin and heterogeneous characteristics of the tumor were associated with the macroscopic type of cut surface and INF. The infiltrative cancerous extension was especially reflective of the margin irregularity of the tumor on CE-CT. On the delayed CT scan performed on 9 patients, the low density tumor on early contrast enhanced CT became isodense with the surrounding parenchyma. According to these findings, the possibility exists that delayed contrast enhancement relate to fibrous tissue. In conclusion, there was a good correlation between CT images and histopathological findings related to pancreatic carcinomas. PMID- 1613066 TI - [Investigation of "reading" with FFT analysis of the beta waves in EEG during "rapid-reading"]. AB - The beta waves in electroencephalograms (EEGs) during "reading" were investigated by means of the Fast Fourier Transform (FFT) analysis method. The subjects who had mastered a "rapid-reading" method, were classified into two groups according to their rapid-reading achievement level: the "under-trained readers" (male 5, female 2) had already acquired the ability of smooth eye movement, but continued to use the mental phonetic process while reading. The "well-trained readers" (male 6, female 2) could understand the contents of the text without resorting to such phonetic process. All subjects were righthanded. The tasks were designed to eliminate the artifact of the eye movement and the electromyogram as much as possible. The EEGs were recorded with twelve channels of the international standard 10-20 electrode system. The relative power value (R.P.V.) was calculated as follows: RPV(%) = [(X-C)/N] x 100(%) where X is the beta 1 or beta 2 power value by FFT analysis while doing tasks, C is the power value while doing control tasks, and N is the value in the resting state with the eyes open. The results were statistically analyzed by paired t-test. The following results were obtained: In both groups; (a) the left angular gyrus was usually activate during the rapid-reading; (b) the Wernicke's center was activated only during reading with the phonetic process; (c) in the well-trained readers the activation of the right visual cortex was associated with some visual imaging during the rapid reading; (d) in the under-trained readers, the association between the activation of the central frontal area and the rapid-reading was observed. Thus, the following model for "reading" was obtained: Two parallel pathways seem important in the processing of the verbal information presented visually; one relates only to the left angular gyrus where the visual-verbal information is processed directly, and the other relates to the interactive pathway between the left angular gyrus and the Wernicke's center. Moreover, the visual cortex of the non verbal hemisphere seems to play some role in understanding verbal information. PMID- 1613067 TI - [Purification and characterization of the membrane associated calmodulin from the human placenta]. AB - The protein with the most predominant Ca2+ binding activity in membrane fractions of the human placenta was purified to electrophoretical homogeneity. This protein was identified as the membrane bound form of calmodulin based on the immunological cross reactivity and a number of biochemical properties. The membrane fraction of the human placenta contained 8.3% of the total cellular calmodulin activity. Approximately 2/3 of the membrane associated calmodulin was extracted by incubation with a Ca2+ chelating agent, EGTA, suggesting that this form of calmodulin is bound reversibly to membrane proteins in a Ca2+ dependent manner. However, the rest of the membrane associated calmodulin could not be extracted by EGTA treatment. The EGTA nonextractable calmodulin appears to be embedded in the membrane matrix. PMID- 1613068 TI - [Tetanus. A report of an aged severe case and review of the literature]. PMID- 1613069 TI - [Endoscopic polypectomy in gut, especially in the colon and rectum]. PMID- 1613070 TI - [Supplement of CT evaluation on staging of rectal carcinoma]. AB - Preoperative pelvic computed tomographic (CT) images were analyzed in 50 patients with rectal carcinoma to evaluate the depth of mural invasion. Firstly the rectum was inflated with air. Secondly cross-sectional CT images of the rectal carcinoma were taken, in all cases referring to lateral scout view films and barium enema films. The circle rate of the tumor was determined in the cross-sectional image. Perirectal changes on CT were evaluated where there were spiculated and nodular appearances. The circle rate correlated with the extent of mural invasion. In cases within 1/3 circle in the circle rate and without perirectal nodular appearance, more than 90% of the tumors were limited to the muscularis propria of the rectal wall. These findings were very useful for assessing suitable surgical treatment. PMID- 1613071 TI - [Hyperlipidemia. How to make a diagnosis and appropriate prescription]. PMID- 1613072 TI - The survival rate of macrophages in prostatic fluid from nonbacterial prostatitis patients. PMID- 1613073 TI - Alcohol and smokeless tobacco effects on the CD-1 mouse fetus. AB - Tobacco products and alcohol are commonly used as nonmedicinal drugs by pregnant women, and both are known to cause various effects on the fetus and the newborn. The objective of this study was to examine the fetal effects of both drugs when administered individually and simultaneously to pregnant CD-1 mice at moderate dosages. Specifically, we wanted to determine whether or not the effect on the fetus of these two biologically active substances was additive, ameliorative, or synergistic. A total of 65 CD-1 dams were divided among four groups receiving either ST equivalent to 8 mg/kg nicotine, ethanol (ETOH) 1.8 g/kg, a combination of ST+ETOH in the same dosages, or D-glucose (controls and ST alone) to supply calories equivalent to the dose of ethanol. Mice were dosed three times per day on gestational days 6-15. On gestational day 17 all dams were killed, fetal and placental weights recorded, and the number of resorbed, dead, and malformed fetuses noted. The mean maternal plasma drug levels were: nicotine-321 ng/ml and ethanol-0.105 g%. No significant differences were observed in maternal weight gain, litter size, or in the incidence of resorptions, deaths and/or malformations. Fetal weights were reduced in all three treatment groups (P less than 0.05), with the greatest reduction (13% decrease) recorded in the ST group, followed by a 9% decrease in the ETOH group, and a 7% decrease in the ST+ETOH group. Placentas of the ST group weighed significantly less (P less than 0.05) than controls. Ossification of the fetal skeleton, observed in ten sites, was affected to the greatest extent in the ST group, followed by the ETOH and ST+ETOH groups. Craniofacial measurements were significantly affected (P less than 0.05) in all three treatment groups, compared to controls. We conclude that under these experimental conditions, in terms of fetal growth and ossification, ST had the greatest effect, followed by ETOH and ST+ETOH. The interaction of ST+ETOH was neither additive, synergistic, nor ameliorative. PMID- 1613074 TI - Everything's got a moral, if only you can find it. PMID- 1613075 TI - Altered retinoid distribution in the repeated epilation (Er) mutant mouse. AB - The repeated epilation (Er) mutation in mice causes successive loss and regrowth of hair in heterozygotes (Er/+), and blocks orofacial development and epidermal differentiation in lethal homozygotes (Er/Er). Because the mutation affects a systemic factor, because the Er phenotypes resemble exposure to excess retinoids and because retinoids are critical regulators of epithelial differentiation, we examined whether systemic retinoid levels are altered by the Er defect. Liver retinoic acid and retinol were elevated 1.5- and 3.5-fold, respectively, in adult heterozygotes (Er/+) compared to normal (+/+) animals. Retinyl palmitate was increased 2-fold in heterozygous skin and 3-fold in kidney, but the retinol level in plasma was only half that of normal animals. Newborn heterozygous liver also had nearly 2-fold increased retinoids compared to normal. In contrast, Er/Er newborns had reduced retinoid levels in liver, two-thirds the retinol and 15% the retinyl palmitate compared to normal, but greater than 4-fold elevated levels of retinyl palmitate in the extrahepatic body. Tissue contents of retinol binding protein (RBP), which transports vitamin A from the liver to the remainder of the body, were determined by immunoblotting with anti-mouse RBP. Newborn normal and mutant animals had similar liver microsomal RBP contents. RBP contents in plasma and in liver microsomes were also similar in normal and Er/+ adults despite different retinol contents in the Er/+ tissues. Hair follicles of the Er/+, but not the normal adult, were stained with this antiserum to RPB in the outer root sheath layer. These results strongly suggest that altered retinoid distribution is associated with, and may be responsible for, the altered epithelial differentiation in the Er mutant. PMID- 1613077 TI - The distribution of syndecan during murine secondary palate morphogenesis. AB - The distribution of syndecan, an integral membrane proteoglycan, has been immunohistochemically mapped during the course of murine secondary palate morphogenesis, gestational days 12-15. Syndecan has been shown to mediate cell adhesion and shape change and to be involved in epithelial-mesenchymal interactions during the morphogenesis of several structures. Changes in epithelial cell architecture accompany and may serve to direct the reorientation of the murine secondary palatal shelves from a vertical position on either side of the tongue to a horizontal and adhering position above it. Using a monoclonal antibody made to the core protein of the ectodomain of syndecan, staining was observed to correlate with epithelial cell shape, packing and degree of differentiation. Staining of condensing mesenchyme was also observed. Syndecan may be involved in modulating epithelial cell shape, architecture and fates during both major phases of secondary palate morphogenesis: shelf reorientation and midline epithelial seam dissolution. PMID- 1613076 TI - Chromosomal localization of the retinol binding protein gene and its elimination as a candidate gene for the repeated epilation (Er) mutation in mice. AB - The repeated epilation (Er) mutation is an autosomal defect that blocks differentiation in stratified epithelia and appendages in mice. Plasma retinol binding protein (RBP) was tested as a possible candidate gene for the Er defect because of the importance of retinol as a modulator of epithelial morphogenesis and differentiation. Two approaches were used: (1) cloning and sequencing of the RBP cDNA from normal and mutant mice, and (2) the chromosomal localization of the mouse RBP gene. The mouse RBP sequence differs slightly from that of the rat RBP, but mutant and normal mouse RBP have identical sequences. The mouse RBP gene was localized by in situ hybridization to the distal portion of chromosome 19. This physical mapping confirms the recent assignment of the gene to chromosome 19 by linkage analysis. These results eliminate the RBP gene as a candidate gene for the defect in the Er mutation that maps to chromosome 4. PMID- 1613078 TI - Staurosporine, a protein kinase inhibitor, stimulates cartilage differentiation by embryonic facial mesenchyme. AB - We have examined the effects of staurosporine, a potent inhibitor of protein kinase C, on cartilage differentiation in cultured mesenchyme of embryonic facial primordia. Mesenchymal cells from the frontonasal, maxillary, and mandibular processes and hyoid arches of stage 24/25 chicken embryos were maintained in high density micromass cell cultures in the presence or absence of 5 nM staurosporine. In cultures of frontonasal and mandibular process mesenchyme, which spontaneously developed numerous chondrogenic cell aggregates, staurosporine treatment enhanced Alcian blue-positive matrix accumulation, increased pericellular sulfated glycosaminoglycan (GAG) deposition by 5.8- and 2.7-fold, respectively, and elevated cytoplasmic levels of cartilage-specific proteoglycan mRNA. In maxillary process mesenchyme, which formed little cartilage matrix under control culture conditions, staurosporine treatment stimulated extensive cartilage nodule formation, promoted a 5.4-fold rise in matrix GAG accumulation, and increased expression of both type II collagen and cartilage proteoglycan mRNA. Moreover, staurosporine treatment initiated chondrocyte differentiation and induced the expression of type II collagen and cartilage proteoglycan gene transcripts in hyoid arch mesenchyme, which exhibited no spontaneous chondrogenesis in control cultures. The results demonstrate that staurosporine promotes cartilage formation in embryonic facial mesenchyme, and suggest the possibility that protein kinase C might function as an inhibitory modulator of chondrocyte differentiation in the neural crest-derived progenitor cells of the embryonic facial skeleton. PMID- 1613079 TI - Metabolic transitions in rat jaw muscles during postnatal development. AB - The program of acquisition of adult metabolic phenotypes was studied in three jaw muscles in order to determine the link between muscle metabolism and functional development. During early postnatal stages, there were similar transitions in the masseter, anterior digastric, and internal pterygoid muscles with respect to fiber growth, fiber type composition, and whole muscle energy metabolism. Oxidative capacity, as judged by the activities of the enzymes succinate dehydrogenase (SDH), malate dehydrogenase (MDH), and beta-hydroxyacyl CoA dehydrogenase (beta OAC), rose sharply after birth to reach near maximal levels by 3 weeks. The capacities for glycolytic metabolism represented by lactate dehydrogenase (LDH), and for high-energy phosphate metabolism represented by adenylokinase (AK) and creatine kinase (CK) activities, rose gradually, not reaching peak values until 6 weeks or later. Thus, the maturation of oxidative metabolism preceded that of glycolytic metabolism in the developing jaw muscles. This was documented for individual fibers in the masseter muscle. Differential metabolic maturation among the jaw muscles was evident beyond 3 weeks. All three jaw muscles attained their specific adult fiber-type profile by about 6 weeks. This maturation program differed from that of hindlimb muscles [Nemeth et al., J Neurosci 9:2336-2343, 1989] and diaphragm muscle [Kelly et al., J Neurosci 11:1231-1242, 1991], reflecting their differential energy demands for contractile performance. PMID- 1613080 TI - Natural history of ultrasound hip abnormalities in clinically normal newborns. AB - One hundred one clinically normal newborn hips showed varying degrees of sonographic hip dysplasia according to the classification of Graf. None were treated, and after +/- 6 months, radiographs showed that only four had definite dysplasia. Of these, three had had risk factors such as breech delivery or familial predisposition. Forty-three other clinically normal newborn hips showed ultrasonic instability, which spontaneously corrected. The severity of ultrasound dysplasia at birth was not related to ultimate development of the hip. Our results indicate that ultrasound should not be performed as a general screening procedure in clinically normal newborns. PMID- 1613082 TI - Second operation for slipped capital femoral epiphysis: pin removal. AB - Pin removal procedures were retrospectively reviewed for 43 hips in 31 patients. Original treatment had included use of Knowles, Steinmann, Hagie, and cannulated steel pins. Time to pin extraction ranged from 5 to 70 months. Average operative time was slightly more than 1 h and average blood loss was 127 ml. Bone overgrowth and difficult extraction was encountered with all pin types. Pin breakage during extraction was recorded with Steinmann and Knowles pins. Delay in return to full activity postoperatively was a common complaint. This study shows that pin removal is not without certain costs and risks. PMID- 1613081 TI - Role of pin protrusion in the etiology of chondrolysis: a surgical model with radiographic, histologic, and biochemical analysis. AB - We studied a model of pin protrusion in rabbit hips to determine if chondrolysis is produced. Enzymatic degradation of the articular cartilage remote from the pin site and mechanical destruction of the acetabulum occurred. Loss of proteoglycans in the articular cartilage averaged approximately 30%, and matched the increase in neutral protease activity. This presumably accounts for the loss of height that occurs in chondrolysis, but throughout the study, the joint space did not narrow; instead, it increased. This suggests that some other factor is needed to produce chondrolysis, such as a slip or an immune response. PMID- 1613083 TI - Remodeling in slipped capital femoral epiphysis: sonographic assessment after pinning. AB - Twenty-one children and 26 hips with recent slipped capital femoral epiphysis (SCFE) underwent serial sonographic examination after operative fixation. The initial sonographic step at the anterior outline of physis decreased as a result of metaphyseal resorption. The first signs of resorption were evident 3 weeks after onset of symptoms; thereafter, the rate of resorption was 2 mm for each 3 weeks of follow-up. Finally, the physeal step was smooth and the anterior aspect of the femoral neck was straight. Sonography is accurate and free of projectional errors in assessment and classification of remodeling in SCFE. PMID- 1613084 TI - Slipped capital femoral epiphysis in black children: incidence of chondrolysis. AB - The risk of chondrolysis and avascular necrosis (AVN) in black children treated for slipped capital femoral epiphysis (SCFE) is controversial. A retrospective study was conducted of 29 black patients (44 hips) treated for SCFE at Kings County Hospital, Brooklyn, New York, to evaluate our own experience. All patients were treated with in situ pinning. The overall rates of chondrolysis and AVN were 6.8 and 4.5%, respectively. Fifty-two percent of patients had bilateral SCFE. Obesity was extremely common and correlated significantly with bilateral disease. Obesity did not correlate directly with a higher incidence of chondrolysis or AVN. Adherence to technical details described should reduce complications further. PMID- 1613085 TI - Results of the Kalamchi modification of salter osteotomy in the treatment of developmental dysplasia of the hip. AB - The results of the Kalamchi osteotomy for acetabular dysplasia or subluxation secondary to developmental dysplasia of the hip are reported. In 16 hips, the modified innominate osteotomy was the sole procedure, whereas 10 hips had a concomitant shelf procedure and four hips had a concomitant femoral varus osteotomy. Using a modification of Severin's classification for radiographic evaluation, 97% of hips were classified as excellent (class I and II). Using McKay's criteria for clinical results, 93% of hips were classified as excellent or good. The advantages of this procedure are avoidance of limb lengthening, better stability of the osteotomy, no need for graft, and theoretically a decrease in pressure across the femoral head. PMID- 1613086 TI - Pediatric spine tumors with spinal cord compromise. AB - Twenty-nine pediatric spine tumor patients with neurologic deficit were reviewed retrospectively to evaluate tumor control, neurologic course, spinal deformity, and response to treatment. Diagnoses included 10 neuroblastomas, nine sarcomas, eight astrocytomas, and two lymphomas. Mean duration of symptoms at presentation was 8 weeks. Mean clinical follow-up was 7 years 4 months, with patient survival of 66% and a local recurrence rate of 34%. Twenty-four percent (seven of 29) of patients recovered minimal neurologic function with treatment, 76% (22 of 29) showed significant recovery, and two thirds (20 of 29) developed spinal deformity. The initial clinical response to chemotherapy appeared to be most pronounced in sarcoma patients (66% positive response). PMID- 1613087 TI - Calcaneus deformity in spina bifida: results of anterolateral release. AB - We reviewed a group of patients with 76 feet treated operatively for a calcaneus or a calcaneovalgus deformity by a simple anterior (tenotomy of the tibialis anterior, extensor digitorum communis and extensor hallucis longus), or anterolateral (associated tenotomy of the peroneus longus and brevis) release. The results were assessed considering bracing and shoewear problems or presence of pressure sores. The mean follow-up time was 4.66 years, and a good result was achieved in 62 feet (81.5%), with 14 poor results in 18.5%. Among the 14 poor results, six deformities have recurred and were operatively treated by the same technique and eight feet developed an equinus deformity requiring a heel cord release. PMID- 1613088 TI - Spinal fusions to the pelvis augmented by Cotrel-Dubousset instrumentation for neuromuscular scoliosis. AB - Eighteen patients with spinal deformity secondary to a neuromuscular disorder were treated with posterior fusion using Cotrel-Dubousset instrumentation (CDI) to the pelvis. The mean frontal plane curve was 70 degrees preoperatively and 38 degrees postoperatively. The mean loss of correction was 3 degrees at an average follow-up of 28 months. Pelvic obliquity improved in nine patients from a preoperative mean of 22 degrees to 11 degrees at follow-up. Lumbar lordosis was maintained with preoperative and postoperative means of -36 degrees. Complications included perioperative hardware failure in one case and one late, deep infection. There were no neurologic complications, pseudarthroses, or rod breakage. Posterior spinal fusion with CDI to the pelvis is an effective treatment for patients with neuromuscular scoliosis. PMID- 1613089 TI - Soft Boston orthosis in management of neuromuscular scoliosis: a preliminary report. AB - Collapsing neuromuscular spinal curvature is extremely difficult to manage with standard rigid orthoses owing to skin breakdown and patient intolerance. Experience with a new, more malleable type of spinal brace (the "soft Boston orthosis") has been very rewarding in 55 children with neuromuscular scoliosis with an average curvature of 42 degrees. Patient tolerance was improved in 38%, patient handling was facilitated in 68%, and postural positioning was enhanced in 79%. Although improvement in the scoliosis averaged only 15 degrees, the major advantage of this orthosis was a marked improvement in sitting stability in 80% of patients. PMID- 1613090 TI - Criteria for selective fusion in idiopathic scoliosis using Cotrel-Dubousset instrumentation. AB - Spinal decompensation after Cotrel-Dubousset (C-D) instrumentation in the King type II curve pattern has become a recognized complication secondary to progression of the unfused lumbar curve. Twenty-three patients with type II curves who underwent selective thoracic fusion according to the guidelines established by King et al. were reviewed. Mean follow-up was 19.5 months. Lumbar curves greater than 45 degrees associated with a low flexibility index were significantly more likely to develop postoperative progression of the uninstrumented lumbar curve with resultant spinal decompensation, suggesting that in these curves the King criteria for selective thoracic fusion may not be appropriate. PMID- 1613091 TI - Prevalence of trunk abnormalities in eleven-year-old schoolchildren in Rotterdam, The Netherlands. AB - The prevalence of trunk abnormalities was studied in 4,915 children aged 11 years (2,528 boys, 2,387 girls); 33% of the children were of non-Dutch origin. The following measurements were recorded: height, weight, signs of puberty, and menarche. Trunk abnormality was assessed in the erect child (asymmetry of shoulders, waistline, imbalance of the trunk, scoliosis, lordosis, kyphosis, swayback, and flexibility) and by the forward bending test (rib hump or lumbar prominence, persistence of scoliosis, kyphosis, deviant lateral aspect); 85.9% of boys and 81.3% of girls were symmetric, and abnormal forward bending test was noted in 7.1% of boys and 10.6% of girls. In non-Dutch girls, trunk abnormalities were more prevalent. PMID- 1613092 TI - Medial spinal aplasia--a rare manifestation of congenital paraplegia: report of six cases and review of the literature. AB - Medial aplasia of the spine is a rarely recognized malformation characterized by isolated absence of spinal segments, with vertebrae present cranially and caudally. We analyzed six patients and the five cases described in the relevant literature. The extent of defect ranges from one to 11 segments and leads to spinal instability with resulting kyphosis. All patients have a thoracic or high lumbar level of paralysis and, in varying degrees, typical contractures of hips, knees, and feet. The differentiation between medial aplasia of the spine and the syndrome of caudal regression is discussed. PMID- 1613093 TI - Humeral torsional deformity after supracondylar osteotomy for cubitus varus: its influence on the postosteotomy carrying angle. AB - Humeral torsion was measured in 23 patients by computed tomography (CT) scan after supracondylar osteotomy for cubitus varus. The opposite unoperated humerus was used as the control. The mean torsion in the unoperated humerus was 70 degrees. Patients who did not have "derotation" of the distal fragment during osteotomy had approximately 30 degrees more internal torsion on the operated side than on the opposite side. The carrying angle after osteotomy was not influenced by lack of correction of torsional deformity in the humerus, and correction of torsion during osteotomy was not essential for correction of the carrying angle. PMID- 1613094 TI - Deformity and function in supracondylar fractures of the humerus in children variously treated by closed reduction and splinting, traction, and percutaneous pinning. AB - The radiographs of 137 patients with supracondylar fractures of the humerus treated by closed reduction and splinting, traction, and closed reduction and percutaneous pinning (CRPP) were reviewed to determine the adequacy of the initial reduction and the maintenance of the reduction. Eighty-four patients were examined for function and deformity. Initially, Baumann's angle was adequate and similar in all patients, but the humerocapitellar angle was better with CRPP. Maintenance of reduction in both planes was superior with CRPP, and significantly better clinical results were achieved by CRPP. Nevertheless, there was no functional loss in any patient, and no parent wanted correction of deformity. PMID- 1613095 TI - Femoral shaft fractures in children: an epidemiological study in a Danish urban population, 1977-86. AB - We report 144 femoral shaft fractures (FSF) in 138 children less than 15 years old. The boy/girl ratio was 2.8:1. The incidence rate was 28 per 100,000 child years. Young children (less than 3 years) had the highest incidence rates. The most common etiology was trauma due to traffic accidents (43.1%) and falls (42.2%). Falling off bicycles contributed to 4.9%, direct trauma to 3.5%, and jamming to 5.6% of fractures. Involvement of children in traffic accidents and the number of FSFs due to traffic trauma fell significantly during the study period. The resource consumption of FSF was very high compared to other childhood fractures. The mean length of stay for FSF was almost three times that of all other patients seen in the emergency unit. PMID- 1613096 TI - Complications associated with fracture of the neck of the femur in children. AB - We reviewed 16 children with 16 displaced fractures of the femoral neck associated with complications. One was a transepiphyseal fracture, 12 were transcervical fractures, and three were basocervical fractures. The mean age at time of fracture was 11 years 7 months (range, 4 years 6 months to 16 years), and the mean length of follow-up after fracture was 6 years 11 months (range, 2-24 years). Complications in this series were avascular necrosis (AVN) (14 patients), nonunion (seven patients), premature physeal closure (15 patients), chondrolysis (seven patients), and coxa vara (two patients). Avascular necrosis, nonunion, and chondrolysis were associated with a poor outcome. Coxa vara or premature physeal closure alone was not responsible for a poor result. PMID- 1613097 TI - Physiologic changes during tourniquet use in children. AB - The hemodynamic and metabolic effects of unilateral tourniquet use were assessed in 30 children. Intraoperative hyperthermia, tachycardia, endtidal CO2, and lactic acid concentration were measured before and after tourniquet inflation. Maximum changes in temperature and pulse rate occurred in patients who had tourniquet application time lasting greater than 75 min. Lactate and endtidal CO2 levels were also significantly increased in the same group of patients. PMID- 1613098 TI - Noninvasive vascular studies in clubfoot. AB - A two-phase study investigated vascularity in idiopathic clubfeet (talipes equinovarus, TEV) undergoing a comprehensive soft tissue release. Great toe O2 saturation was measured by pulse oximetry in a consecutive series of 50 TEV (34 patients) in three foot positions: in feet at rest, in feet in maximal passive correction, and in feet immediately postoperatively. Oxygen saturation was between 94 and 100% in 100% of feet at rest, 95-100% in 90% of feet at maximal passive correction, 95-100% in 98% of feet immediately postoperatively, and 97 100% in 100% of feet 3 weeks' postoperatively. Doppler ultrasound studies were performed on 38 TEV. Dorsalis pedis (DP), posterior tibial (PT), and peroneal (P) pulses were recorded at preoperative resting posture, preoperative maximal passive correction, and 3 weeks postoperatively. At rest, DP pulse was present in 37 of 38 feet, PT pulse was present in all feet, and P pulse was present in 20 of 30 tested (67%), whereas 72% PT, 61% DP, and 50% P pulses were unchanged. Pulse oximetry and Doppler assessment are readily available, noninvasive, and reproducible means of monitoring vascular integrity in TEV. PMID- 1613099 TI - Ankle-foot orthosis function in low-level myelomeningocele. AB - Six children with low-level myelomeningocele underwent gait analysis. All showed excessive ankle dorsiflexion and knee flexion when walking barefoot. A rigid thermoplastic ankle-foot orthosis (AFO) improved gait by preventing ankle dorsiflexion and reducing knee flexion. Biomechanically, the AFO caused a reduction in external knee moment by aligning the knee with the ground reaction force. Small changes in the foot-shank angle of the orthosis had profound effects on knee mechanics. Knee hyperextension could be controlled by a rocker sole. Kinetic gait analysis permits understanding of the biomechanical effects of orthoses. PMID- 1613100 TI - Wave pattern of ground reaction force of growing children. AB - We studied the free gait of children by analyzing the wave pattern of the ground reaction force (GRF) and measuring time and distance parameters using large force plates. Two hundred and forty-one normal children, age 4-10 years, were included. Normalized waves of each subject were obtained by computer. Waves are composed of fore-aft, medial-lateral, and vertical components. We took nine specific points on these waves and analyzed the values of specific points and time and distance measurements. We found significant changes of these parameters up to approximately 8 years of age. These findings serve as GRF control data and are useful in evaluating pathological gaits. PMID- 1613101 TI - Orthopaedic aspects of children with infectious (central nervous system) postnatal cerebral palsy. AB - Twenty-two children (15 girls, 7 boys) with postnatal infectious cerebral palsy were reviewed at an average age of 8 years. Orthopaedic deformities were noted in 82% of all children and involved the upper extremity (41%), spine (45%), hips (68%), knees (32%), and feet and ankles (55%). Both typical and atypical cerebral palsy deformities were noted, often severe. Surgical correction of deformities achieved 77% satisfactory results. Bony procedures did better than soft tissue procedures, especially around the hip. PMID- 1613102 TI - Salmonella osteomyelitis and the hand-foot syndrome in sickle cell disease. AB - I investigated 11 cases of hand-foot syndrome, three of which were associated with Salmonella osteomyelitis. These three cases are described to highlight the difficulty in differentiating infection from infarction in the hand-foot syndrome. PMID- 1613103 TI - The popliteal artery entrapment syndrome in children. AB - This article reviews 41 cases of the popliteal artery entrapment syndrome in individuals less than 20 years of age. In this syndrome, symptoms are caused by vascular insufficiency produced by either an anomalous course of the popliteal artery or anomalous muscles impinging upon it. Because vascular insufficiency is uncommon in orthopedic patients in this age group and this syndrome has received little attention in the orthopedic literature, orthopedists unfamiliar with this relatively easily diagnosed condition may miss it. PMID- 1613104 TI - Fat embolism as a complication of closed femoral shortening. AB - Although closed femoral osteotomy for shortening or correction of deformity is not a new procedure, its popularity apparently is increasing. We have encountered a serious "biological" complication that should be considered before this technique is selected. Two patients, a 12-year-old girl and an 18-year-old man, developed findings consistent with the fat embolism syndrome after closed femoral shortening. We suggest consideration of postoperative monitoring with pulse oximetry of patients undergoing this procedure. PMID- 1613105 TI - Arthroscopic visualization during excision of a central physeal bar. AB - A centrally located developmental physeal bar in the proximal tibia was removed via a metaphyseal window. The use of an arthroscope to assist in the complete removal of the bone bridge is described. The arthroscope improved visualization and allowed reduction in the size of the metaphyseal window. At 2-year follow-up, the growth plate showed no evidence of bar reformation. PMID- 1613106 TI - Allograft versus autograft bone in idiopathic scoliosis surgery: a multivariate statistical analysis. PMID- 1613107 TI - The chin as a donor site in early secondary osteoplasty: a retrospective clinical and radiological evaluation. AB - 26 unilateral cleft palate patients received an autogenous bicortical chin bone graft for early reconstruction of the alveolar process. In the evaluation of the donor site, 4% of the anterior teeth showed a negative pulpal sensibility, less than 1% a peri-apical granuloma and 12% pulp canal obliteration. The tooth buds of the canines showed developmental disturbances in 6%. Exposure of unerupted canines should be avoided, and a 5 mm safety margin is advised. Based on its architecture, topographic accessibility, minimal post-operative morbidity and absence of visible scars, the chin can be considered to be a very useful donor site in bone grafting procedures. PMID- 1613108 TI - Three-dimensional craniofacial surgery: transfer from a three-dimensional model (Endoplan) to clinical surgery: a new technique (Graz). AB - A new technique of individual, three-dimensional (3-D) planning and transferring this to craniofacial operations is reported. The combination of an individual model of the skull of the patient with a transfer device enables planning of real 3-D surgery. The surgical technique is demonstrated in a case with an asymmetrical midface and mandible after ankylosis of the TMJ in childhood. PMID- 1613109 TI - Improvements in morbidity of mouth cancer using microvascular free flap reconstructions. AB - 50 patients who underwent major surgery for head and neck cancer and reconstructed with radial forearm microvascular free flaps, were assessed with regard to social adaptation, appearance and in particular mouth function. The results were compared with a similar group of patients who underwent reconstruction with either primary repair or pedicled flaps. PMID- 1613110 TI - Traumatic asphyxia compounding craniofacial trauma. AB - Traumatic asphyxia is a condition characterized by cervicofacial petechiae, subconjunctival ecchymosis and other possible accompanying problems particularly ophthalmic, thoracic and cardiovascular injuries. While the facial petechiae per se are of little consequence, the attendant injuries to other organ systems can be serious and even fatal. Craniofacial injuries also present with fatal ecchymosis and haematoma formation due to the underlying skeletal injuries which may require active management. Clinicians managing trauma patients should be well aware of these two different entities which may occur separately or simultaneously so as to ensure correct and adequate treatment. PMID- 1613111 TI - Latham's appliance for presurgical repositioning of the protruded premaxilla in bilateral cleft lip and palate. AB - Dislocation of the maxillary segments in cleft lip and palate still is a challenge to the surgeon and the orthodontist. The premaxillary protrusion in bilateral cleft lip and palate, complicates the treatment severely. Latham's appliance, inserted on average at 2-months-of-age, relocates the segments over 3 4 weeks. Removal of the appliance is immediately followed by functional surgery. The first operation comprises: (1) intra-alveolar veloplasty; (2) closure of the alveolar cleft with the help of a gingivo-periosteal-plasty; (3) lip adhesion and (4) insertion of ear tubes. This operating schedule establishes the functional matrix as early as possible. Midfacial growth as well as language and speech development are provided with the necessary preconditions as far as we understand this complex situation. Five cases, being representative of 41 cases, are outlined in detail. The longest follow up period is 3 years; no growth disturbance of the maxilla has been detected to date. Definitive lip and columella surgery is facilitated. PMID- 1613112 TI - Anglo- and Mexican-American preschoolers at home and at recess: activity patterns and environmental influences. AB - Habitual physical activity in children is related to physical fitness and appears to mediate cardiovascular disease (CVD) risk factors. We studied the physical activity patterns and associated variables of a large bi-ethnic cohort of 4-year old children from low to middle socioeconomic families. Trained observers coded the behavior of 351 children (150 Anglo-American, 201 Mexican-American; 182 boys, 169 girls) during two 60-minute home visits and two unstructured recesses lasting up to 30 minutes each at 63 different preschools. Findings indicated that although children were much less active at home, there were low but significant correlations between their activity patterns at home and during recess (r = .13). Children who had activity-promoting toys at home also tended to have them available during preschool recess (r = .20). Ethnic differences were evident for both activity and environmental variables. Mexican-American children were less active than Anglo children at home (p less than .002) and during recess (p less than .03), thus adding to the adult literature that has found Mexican-Americans to be less active than Anglos, and supporting to the notion that physical activity life-style habits may be established in early childhood. In both settings, Mexican-American children spent more time in presence of adults (home, p less than .04; recess, p less than .03) and had access to fewer active toys (home, p less than .001; recess, p less than .05). Gender differences were also evident for both activity and environmental variables.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613113 TI - Parents' knowledge of neonatal screening and response to false-positive cystic fibrosis testing. AB - Neonatal screening for cystic fibrosis (CF) has become feasible through analyzing dried blood specimens for immunoreactive trypsinogen (IRT), but the benefits and risks of such a screening program remain to be delineated. This study, a survey of the parents of 104 Wisconsin infants with false-positive IRT tests, showed parents had knowledge deficits about neonatal screening in general, misconceptions about test results, and high levels of anxiety. Parenting behaviors were reportedly unchanged during the usual 3-day waiting period between the news of the abnormal screening test and the diagnostic sweat test. Most, but not all, parents were relieved by negative sweat test results subsequent to the abnormal IRT test. Factors associated with continued parental concern included having less than a high school education and/or having an infant with low Apgar scores. Additionally, those contacted by telephone were more likely to have misinformation and lingering concerns about the presence of CF in their child. PMID- 1613114 TI - Social interactions between children with cancer or sickle cell disease and their peers: teacher ratings. AB - We evaluated the social reputation of children with cancer (nonprimary brain tumors) (n = 26) children with a primary malignancy involving the central nervous system (n = 15), and children with sickle cell disease (SCD) (n = 33) using a standardized measure of social reputation, the Revised Class Play (RCP). Each child's classroom teacher completed the RCP, an instrument designed to assess sociability-leadership, aggressive-disruptive, and sensitive-isolated interpersonal qualities. Matched-pairs analyses comparing the child with chronic illness to one peer in each class who was the same gender/race and the closest date of birth showed children with cancer were nominated more often for sociability-leadership roles and less often for aggressive-disruptive roles. Brain tumor survivors were nominated more often for sensitive-isolated roles. Children with SCD were not significantly different from peers. Findings suggest that the stressful life events associated with cancer or SCD did not have a significant negative impact on social adjustment for school-aged children with these diseases. The data demonstrate the critical need for appropriate controls when evaluating psychosocial morbidity and chronic illness. Better understanding of the processes of resilience for these children who are routinely exposed to heightened stress provides an opportunity to improve the competence of other high risk youth. PMID- 1613115 TI - Diabetes mellitus in the transition to adulthood: adjustment, self-care, and health status. AB - A cross-sectional study of health and adjustment among 18 to 22-year-old patients with insulin-dependent diabetes mellitus (IDDM) is reported. Objectives were to examine coping with IDDM in this age group; to identify predictors of health status, treatment adherence, and health care use; and to provide a retrospective evaluation of the persistence of IDDM-specific adjustment from earlier through later adolescence. Multiple validated measures, interviews of independent informants, and biochemical assays were used to assess psychological, behavioral, and metabolic status. Patients and parents completed a retrospective measure of the patient's adjustment to IDDM during earlier adolescence. Findings (n = 81) indicated: (1) normal rates of general psychopathology but some evidence of poorer adjustment to IDDM relative to other age groups, (2) poor diabetic control and high incidence of microalbuminuria, (3) specific factors associated differentially with treatment compliance, health care use, diabetic control, and microalbuminuria among late adolescents, and (4) evidence that poor adjustment to IDDM in earlier adolescence persists into the transition to adulthood. The findings imply that late adolescents with IDDM are at risk of various unfavorable behavioral and health outcomes and that adjustment to the disease during earlier adolescence may be a predictor of subsequent health-related behavior and health status. A longitudinal study is needed to confirm these findings. PMID- 1613116 TI - A study of the cognitive aspects of sexual decision making in adolescent females. AB - A comprehensive sexuality questionnaire was administered to 37 females, ages 13 through 16 years, who attended clinics for routine health care. Subjects completed standardized scales of self-concept, locus of control, and future orientation. They also were given a short battery of standardized cognitive tests. Three groups were identified: Group 1 was sexually active and using contraception reliably, Group 2 was not using contraception reliably, and Group 3 had not been sexually active. Group 1 adolescents had higher scores on the vocabulary subtest of the WISC-R (F = 3.4, p less than .05) than did Group 2 adolescents, over and above the effect of socioeconomic status (SES). Group 1 subjects had higher scores on knowledge of sex and contraception than did Group 2 (F = 3.3, p less than .05). Group 1 had more internal locus of control (F = 7.0, p less than .005) than did Group 2 over and above the effect of SES. Mean scores for Group 3 adolescents were intermediate and not significantly different. The findings suggest that cognitive factors may influence contraceptive behavior in adolescent females. PMID- 1613117 TI - The association between hemoglobin and behavior problems in a sample of low income Hispanic preschool children. AB - This cross-sectional study, conducted in 1988, examines the association between hemoglobin level and behavior problems in 236 Hispanic children, ages 2 to 5 years, residing in low-income census tracts in the Los Angeles area. Venous blood samples were analyzed for hemoglobin, mean corpuscular volume, free erythrocyte protoporphyrin, and lead. Family and child data were obtained through a home interview with the child's mother or guardian. Behavior problems were assessed using questionnaires modeled after Child Behavior Checklists for children ages 2 to 3 and 4 to 5 years. A significant correlation between decreasing hemoglobin values and increasing total behavior problems scores was found for girls, 2 to 3 and 4 to 5 years old. These associations remained significant in both age groups after adjusting for maternal education and marital status. Statistically significant inverse correlations also were found between hemoglobin and social withdrawal, sleep problems, and depression (internalizing subscale behaviors) in 2- to 3-year-old girls, and between hemoglobin and aggression and hyperactivity (externalizing subscale behaviors) in 4- to 5-year-old girls. The potentially negative consequences of these anemia-related behavior problems on children's development, learning ability, and parent-child relationships warrant further investigation. PMID- 1613118 TI - Industry-university alliances in biomedical research. PMID- 1613119 TI - Genetic aspects of drug disposition and therapeutics. PMID- 1613120 TI - Pharmacokinetic principles in clinical medicine. PMID- 1613121 TI - Single-dose pharmacokinetics of pravastatin and metabolites in patients with renal impairment. AB - The disposition of a single 20-mg oral dose of pravastatin was assessed in subjects with various degrees of renal function. Sixteen subjects (13 males, 3 females) with creatinine clearance values ranging from 15 to 112 mL/min/1.73 m2 completed the study. Area under the serum concentration-time curve, maximum serum concentration, time to maximum serum concentration, terminal serum elimination half-life, apparent clearance, and apparent volume of distribution for pravastatin were not affected by renal impairment, whereas the renal clearance of pravastatin decreased as creatinine clearance decreased (r2 = 0.697, P less than .001). The area under the serum concentration-time curve and time to maximum serum concentration of SQ 31,945 (a hepatic metabolite) increased in patients with renal impairment, whereas the terminal elimination rate constant and renal clearance of SQ 31,945 significantly decreased as a function of creatinine clearance. The renal clearance of another metabolite (SQ 31,906) also significantly declined with decreasing renal function. This single-dose study demonstrates that pravastatin pharmacokinetics were not affected in patients with renal impairment, probably because of its dual route of elimination. PMID- 1613122 TI - Dose-dependent aspirin hydrolysis and platelet aggregation in patients with atherosclerosis. AB - In a double blind, randomized trial, the effects of aspirin (1, 5, and 15 mg/kg) were compared with the changes in platelet aggregation at 6 and 24 hours after dosage. It is found that there is a negative correlation between aspirin hydrolysis velocity in blood and capability of aspirin to decrease platelet aggregation with ADP and collagen in patients with atherosclerosis. Relationship between these parameters depends on aspirin dosage. The correlation was more marked for low doses of aspirin. It is suggested that the effect of aspirin in low dosage on platelet aggregation might be ineffective in many patients without control of aspirin hydrolysis velocity in blood. PMID- 1613123 TI - Comparative pharmacokinetics of lovastatin, simvastatin and pravastatin in humans. AB - Twelve healthy male volunteers received single market-image 40-mg oral doses of lovastatin and simvastatin (both lactone prodrugs), or pravastatin (a beta hydroxyacid) at 1 week intervals in a three-way crossover study to quantify HMG CoA reductase inhibitors in plasma. Multiple plasma samples were collected up to 24 hours after the dose and assayed for active and total HMG-CoA reductase inhibitors. After equal oral doses, higher plasma concentrations of HMG-CoA reductase inhibitory activity after pravastatin than after either lovastatin of simvastatin (2-3 fold greater area under the concentration-time curve) suggest a greater potential availability of pravastatin-related inhibitory activity to peripheral tissues. PMID- 1613124 TI - Outpatient dobutamine therapy: the rhyme and the riddle. AB - Advances in critical care medicine have increased survival for victims of myocardial infarction and other acute cardiac events so that increasingly patients are receiving long-term, labor-intensive, and costly medical care. Innovations in drug delivery systems and skyrocketing health care costs have fostered the growth of home health care which has blossomed into a $2.8 billion industry. There is evidence that outpatient dobutamine therapy produces definite physical and possibly psychological improvements of variable degree and duration. Hemodynamic improvements are generally associated with improvement in functional class, and the financial savings are recognizably substantial. However, three major problems confront therapies with beta-adrenergic agonists: tendency for tolerance, ventricular arrhythmias, and increased myocardial oxygen consumption. There is a dire need for establishment of exclusionary patient criteria and for risk stratification, as well as for development of a portable radionuclide nonimaging monitor. Given the current fund of knowledge, outpatient dobutamine therapy should be undertaken cautiously after meticulous patient selection reflecting an awareness of the tremendous complexities and inherent risks. The therapeutic implications are dependent on the nature of the underlying cardiomyopathy and the fact that beta-adrenergic receptor desensitization is unlikely to be overcome by progressive dosage increases. Therapy is initiated with the understanding that treatment will remain blindly empirical and conjectural in the absence of a continuous physiologic monitor and an expanded comprehension of the molecular pathophysiology of the failing ventricle. PMID- 1613125 TI - Effect of aging on the pharmacokinetics of acebutolol enantiomers. AB - Acebutolol (AC) is a chiral beta-blocker that is metabolized to an equipotent chiral metabolite, diacetolol (DC). A stereoselective disposition of AC and DC enantiomers has recently been reported in young healthy subjects. As many physiologic properties affecting drug disposition are progressively altered with increasing age, the effect of aging on the pharmacokinetics of AC and DC enantiomers were investigated in nine subjects ranging from 60 to 75 years after administration of an oral 200-mg dose of racemic AC. Increasing age resulted in a significant prolongation of the elimination t1/2s of R- (r = 0.913) and S-DC (r = 0.811). Also, the S:R ratios of AC urinary excretion (sigma Xu) of enantiomers was significantly correlated with age (r = 0.677). Contribution of declining renal function to age-associated pharmacokinetics changes was subsequently examined. Renal clearance and cumulative urinary excretion of both AC and DC enantiomers were positively correlated with creatinine clearance. In addition, declining creatinine clearance was associated with a subsequent decline in the enantiomer S:R ratio of AC in plasma (AUC S:R, r = 0.807) and urine (sigma Xu S:R r = 0.807). Similarly, a progressive decline in the S:R ratio of DC collected in urine was evident (r = 0.689). Age-related changes in the enantiomers ratios may suggest that an active stereoselective pathway such as renal tubular secretion or nonrenal excretion may be affected in the elderly. PMID- 1613126 TI - Influence of food on the absorption of beta-methyldigoxin. AB - Nine healthy subjects received 0.2 mg of beta-methyldigoxin (beta-MD) orally in the fasting state, 30 minutes after and before a standard breakfast. The time-to peak serum glycoside concentration was delayed and the peak concentration was lower in the postprandial state compared with the other regimens (P less than .01). The absorption rate constant was significantly reduced when beta-MD was given after a meal (1.55 +/- 1.75 hr-1) than before a meal (5.54 +/- 2.16 hr-1) and in the fasting state (5.22 +/- 3.06 hr-1)(P less than .01). Although the area under the serum glycoside concentration-time curve and the cumulative urinary excretion (CUE) of beta-MD, digoxin, and total drug (beta-MD plus digoxin) was not significantly different between three regimens, the CUE infinity tended to be smaller in the postprandial state compared with before a meal. The results indicate that the timing of drug administration in relation to a meal is an important factor leading to the fluctuations of serum glycoside concentration after oral beta-MD, which might be of some clinical importance. PMID- 1613127 TI - Investigation of anti-motion sickness drugs in the squirrel monkey. AB - Early attempts to develop an animal model for anti-motion sickness drugs, using dogs and cats; were unsuccessful. Dogs did not show a beneficial effect of scopolamine (probably the best single anti-motion sickness drug for humans thus far) and the findings in cats were not definitive. The authors have developed an animal model using the squirrel monkey (Saimiri sciureus) of the Bolivian phenotype. Unrestrained monkeys in a small lucite cage were tested in an apparatus that induces motion sickness by combining vertical oscillation and horizontal rotation in a visually unrestricted laboratory environment. Signs of motion sickness were scored using a rating scale. Ten susceptible monkeys (weighing 800-1000 g) were given a total of five tests each, to establish the baseline susceptibility level. Based on the anticholinergic activity of scopolamine, the sensitivity of squirrel monkey to scopolamine was investigated, and the appropriate dose of scopolamine for this species was determined. Then various anti-motion sickness preparations were administered in subsequent tests: 100 ug scopolamine per monkey; 140 ug dexedrine; 50 ug scopolamine plus 70 ug dexedrine; 100 ug scopolamine plus 140 ug dexedrine; 3 mg promethazine; 3 mg promethazine plus 3 mg ephedrine. All these preparations were significantly effective in preventing motion sickness in the monkeys. Ephedrine, by itself, which is marginally effective in humans, was ineffective in the monkeys at the doses tried (0.3-6.0 mg). The squirrel monkey appears to be a good animal model for antimotion sickness drugs. Peripherally acting antihistamines such as astemizole and terfenadine were found to be ineffective, whereas flunarizine, and an arginine vasopressin V1 antagonist, showed significant activity in preventing motion sickness. PMID- 1613128 TI - Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. AB - Twelve healthy male subjects completed this randomized, placebo controlled, four period crossover trial to determine the effect of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. Subjects received a 7-day course of one of four treatments; verapamil (120 mg every 8 hr), diltiazem (90 mg every 8 hr), labetalol (200 mg every 12 hr), or placebo (every 12 hr) during each study period. Imipramine (100 mg) was administered orally on the morning of day 4 of each study period. Plasma and urine samples were collected periodically over the ensuing 96 hours. Samples were assayed by HPLC for imipramine, desipramine, 2-hydroxyimipramine, and 2-hydroxydesipramine. Verapamil, diltiazem, and labetalol increased imipramine area under the plasma concentration time curve (relative bioavailability) as compared with placebo by 15%, 30%, and 53%, respectively. Verapamil and diltiazem did not demonstrate consistent changes in the formation of the measured metabolites. Labetalol caused a significant decrease in the amount of imipramine metabolized to 2 hydroxyimipramine (mean decrease: 22%) and from desipramine to 2 hydroxydesipramine (mean decrease: 8%). The molar ratios of plasma AUC of 2 hydroxyimipramine and 2-hydroxydesipramine to the parent compounds were significantly decreased. Since these metabolic processes are dependent on the cytochrome P450IID6 isozyme, these data suggest that labetalol decreases the oral clearance of imipramine by inhibiting this system. All three of these commonly used agents decreased the oral clearance of imipramine. These drug interactions could lead to elevated imipramine concentrations and have the potential for clinically important adverse events. PMID- 1613129 TI - Diurnal effect on caffeine clearance. AB - Caffeine (300 mg) was given orally to nine healthy subjects at 10:00 AM (day trial) or at 10:00 PM (night trial) using a crossover design. Saliva was obtained at 0.5, 1, 1.5, 2, 3, 4, 6, and 8 hours after administration of caffeine. Urine was collected for 8 hours after caffeine dosing. Caffeine clearances in saliva during the day trial were not different from those in the night trial. No significant difference was observed in urinary molar ratios of metabolites (AFMU + 1X + 1U/17U) between the two trials. These data suggest that caffeine clearances in saliva do not vary with its administration time. Since caffeine clearances in plasma are reflected in the urinary ratios of caffeine metabolites, its clearance in plasma might also not be altered by the time of dosing. PMID- 1613131 TI - Effect of bilateral tectum lesions on retinal ganglion cell morphology in rats. AB - We have examined morphological changes of retinal ganglion cells (RGCs) during postnatal development in albino rats. Somatic diameter, dendritic field diameter, and branching frequencies of RGCs of normal rats were compared with those of animals that had received bilateral lesions of the tectum immediately after birth. Bilateral lesions of the tectum at P1 (first postnatal day) induced a dramatic increase in RGC death during the time of naturally occurring cell death in the first postnatal week. RGC densities in adult experimental animals were found to be reduced to about 55% of normal. RGCs of normal and operated animals were retrogradely stained with crystals of the fluorescent dye DiI, which was applied to the optic disc of flat mounted and fixed retinae. In normal rats, the somatic and the dendritic field diameters of the RGCs increased and the branching frequency of type I and III RGCs decreased from P1 to P14. By P14, neither the somatic diameter nor the dendritic field size had yet reached adult values and the branching frequencies were still higher than those of adult rat RGCs. In animals with bilateral lesions of the tectum, all cell types showed an increase in somatic sizes, and in type I and II RGCs an expansion of dendritic territories could be observed. The branching frequencies, however, were significantly lower than those of normal rats of the same age. The dendritic morphology in type III RGCs in operated animals was not significantly different from controls. These findings demonstrate a potential plasticity of type I and II RGCs, which respond to a loss of neighbouring cells by expansion of their dendritic field during postnatal development. PMID- 1613130 TI - The synaptology of parvalbumin-immunoreactive neurons in the primate prefrontal cortex. AB - Electron microscopy and immunocytochemistry with a monoclonal antibody against parvalbumin (PV) were combined to analyze the distribution and morphology of PV immunoreactive (PV-IR) neurons and the synaptology of PV-IR processes in the principal sulcus of the macaque prefrontal cortex. Parvalbumin-IR neurons are present in layers II-VI of the macaque principal sulcus (Walker's area 46) and are concentrated in a band centered around layer IV. PV-IR cells are exclusively non-pyramidal in shape and are morphologically heterogeneous with soma sizes ranging from less than 10 microns to greater than 20 microns. Well-labeled neurons that could be classified on the basis of soma size and dendritic configuration resembled large basket and chandelier cells. A novel finding is that supragranular PV-IR neurons exhibit dendritic patterns with predominantly vertical orientations, whereas infragranular cells exhibit mostly horizontal or oblique dendritic orientations. PV-IR cells within layer IV exhibit a mixture of dendritic arrangements. Vertical rows of PV-IR puncta, 15-30 microns in length, resembling the "cartridges" of chandelier cell axons were most dense in layers II, superficial III, and the granular layer IV but were not observed in the infragranular layers. Cartridges were often present beneath unlabeled, presumed pyramidal cells. PV-IR puncta also formed pericellular nests around pyramidal cell somata and proximal dendrites, suggestive of basket cell innervation. PV-IR axons were occasionally observed in the white matter underlying the principal sulcus. Electron microscopic analysis revealed that PV-IR somata and dendrites are densely innervated by nonimmunoreactive terminals forming asymmetric (Gray type I) synapses as well as by fewer terminals forming symmetric (Gray type II) synapses. The majority of terminals forming symmetric synapses with PV-IR post synaptic structures were not immunolabeled; however, some of these boutons did contain PV-immunoreactivity. PV-IR boutons exclusively form symmetric synapses and heavily innervate layer II/III pyramidal cells. PV-IR axon cartridges formed numerous axo-axonic synapses with the axon initial segments of pyramidal cells 15 20 microns beneath the axon hillock and also terminated on large axonal spines of the initial segment. Furthermore, we failed to observe a mixture of PV immunoreactive and non-immunoreactive boutons composing a single axon cartridge. Pyramidal cell somata and proximal dendrites were also heavily innervated by PV IR boutons forming symmetric synapses, again, consistent with basket cell innervation. In addition, PV-IR axon terminals frequently formed symmetric synapses with dendritic shafts and spines of unidentified neurons.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613132 TI - Vasopressin-immunoreactive neurons and neurohemal systems in cockroaches and mantids. AB - Vasopressin-like neuropeptides of insects are of special interest because of their possible function as hormones and neuromodulators. Therefore, this study was undertaken by using whole-mount immunofluorescent staining by two antisera that recognize different types of vasopressin-like immunoreactive groups of neurons in the cockroaches Periplaneta americana, Leucophaea maderae, Nauphoeta cinerea, Diploptera punctata, and Blaberus discoidalis and in the mantids Litaneuria minor and Tenodera aridifolia sinensis. Using an antiserum to Arg/vasopressin, only two cells, the paired ventral paramedian (PVP) neurons, were immunostained in the central nervous system (CNS) of the cockroaches. These cells are located in the subesophageal ganglion, project throughout the CNS, and appear to be neurosecretory. Their varicose collaterals extend into the dorsal (motor) neuropil of the segmental ganglia, and this neuropil may be the principal site of the release of their neurosecretion. The PVP neurons were also stained by an antiserum to Lys/vasopressin; in addition, this antiserum stained several other groups of neurons, most of which appeared to be neurosecretory. Two pairs of Lys/vasopressin-immunoreactive cells are similar to the PVP neurons in that they are located in the subesophageal ganglion, extend through the ventral nerve cord, have collaterals in the dorsal neuropil of the segmental ganglia, and appear to be neurosecretory within the CNS. In addition, midventral and anteroventral clusters of Lys/vasopressin-immunoreactive neurosecretory neurons in the subesophageal ganglion project neurohemal release sites on the corpora allata. Other types of Lys/vasopressin-immunoreactive neurons include median and lateral neurosecretory cells of the protocerebrum and neurosecretory cells in the tritocerebrum, all of which project to the corpora cardiaca. In the abdominal ganglia there are posterolateral clusters of Lys/vasopressin neurosecretory neurons, and these cells extend to neurohemal release sites on the transverse and lateral cardiac nerves. In mantids the anti-Arg/vasopressin and anti Lys/vasopressin antisera stained most of the same groups of neurons that these antisera recognized in cockroaches. The results of this study suggest that there are two or more vasopressin-like peptides in cockroaches and mantids and that these peptides may be released either as hormones in the blood or as neurosecretions within the CNS. Their function(s) in these insects remains to be determined. PMID- 1613133 TI - Immunocytochemical demonstration of neural cell adhesion molecule (NCAM) along the migration route of luteinizing hormone-releasing hormone (LHRH) neurons in mice. AB - Contact between the developing forebrain and the ingrowing central processes of the olfactory, vomeronasal and terminal nerves is preceded by a migration of neural cell adhesion molecule (NCAM)-immunoreactive cells from the epithelium of the olfactory pit and the formation of an NCAM-immunoreactive cellular aggregate in the mesenchyme between the olfactory pit and the forebrain. The axons of the olfactory, vomeronasal, and terminal nerves, also NCAM-immunoreactive, grow into the cellular aggregate, which as development proceeds, becomes continuous with the rostral tip of the forebrain. The lateral and more rostral part of the cellular aggregate receives the ingrowing axons of the olfactory nerves and becomes the olfactory nerve layer of the olfactory bulb. The medial, more caudal part receives the central processes of the vomeronasal and terminal nerves. The vomeronasal nerve ends in the accessory olfactory bulb. The central processes of the terminal nerve end in the medial forebrain. Luteinizing hormone-releasing hormone (LHRH)-immunoreactive neurons, like the vomeronasal and terminal nerves, originate from the medial part of the olfactory pit. These LHRH cells migrate into the brain along and within a scaffolding formed by the NCAM-immunoreactive axons of the vomeronasal and terminal nerves, and they are never seen independent of this NCAM scaffold as they cross the nasal lamina propria. The results suggest that: (1) NCAM is likely to be necessary for scaffold formation, and (2) the scaffold may be essential for the subsequent migration of LHRH neurons into the brain. Because they aggregate, migrating LHRH-immunoreactive neurons, on which we did not detect NCAM immunoreactivity, may interact via other cell adhesion molecules (CAM). Inasmuch as the interaction between the LHRH-immunoreactive neurons and the NCAM-immunoreactive scaffold is heterotypic, the possibility of a heterophilic (NCAM to other CAM) interaction is not ruled out. These findings focus our attention on the functional role of NCAM in this migratory system. PMID- 1613134 TI - Somatosensory receptive field properties of corpus callosum fibres in the raccoon. AB - Anatomical studies in a number of species have shown that most areas of the somatosensory cortex are callosally interconnected. This is also true for the raccoon, at least for those parts representing proximal and axial body regions. Electrophysiologically, studies carried out in cats and monkeys have demonstrated that all sensory sub-modalities cross in the callosum. Moreover, cells representing the paws and fingers, though occupying a large portion of areas SI and SII, seem to send proportionately fewer axons through the callosum than axial structures. No comparable study has been carried out in the raccoon. The purpose of the present experiment was therefore to investigate the functional organization of the callosal system in this animal by examining the receptive field properties of the somatosensory fibres crossing in the callosum. Axonal activity was recorded directly through tungsten microelectrodes in the corpus callosum of eight raccoons. Results indicated that somatosensory information is transmitted in its rostral portion. Most receptive fields concerned axial and proximal body regions and the head and face. Some receptive fields represented para-axial regions of the body and a few concerned the hands and fingers. Slowly and rapidly adapting fibres were found, as were all the sensory sub-modalities tested. A substantial proportion of the axons had bilateral receptive fields. These results are discussed in relation to those obtained in other species, with particular reference to: (1) the midline fusion hypothesis of callosal function; (2) the representation within this structure of the distal extremities, and (3) the origin of the bilateral receptive fields. PMID- 1613135 TI - Morphology of bipolar cells labeled by DAPI in the rabbit retina. AB - The morphology, distribution, and coverage of certain cone bipolar cell types were investigated in rabbit retina. Brief in vitro incubation of isolated rabbit retina in the fluorescent dye 4,6-diamino-2-phenylindole labeled only a few cell types in the inner nuclear layer. Intracellular injection of Lucifer Yellow into these types showed them to be horizontal cells and cone bipolar cells. All stained bipolar cells ramified in sublamina a of the inner plexiform layer (IPL) and formed three classes. Two types ranged from 20 to 60 microns in diameter in both plexiform layers; the other large bipolar cell was 40-70 microns in diameter in the outer plexiform layer (OPL) and up to 150 microns in diameter in the IPL. The brightest type was narrowly stratified in the outer portion of sublamina a. Its density increased from about 500 cells/mm2 in the periphery to about 2,500 cells/mm2 in the visual streak. Staining of neighboring cells of this type showed that processes in the IPL rarely crossed, but often converged at a common site so as to impart a "honeycomb" appearance to a single sublayer of retina. The other small bipolar cell was similar in density and coverage, but stratified diffusely throughout sublamina a. The large bipolar cell stratified narrowly in the distal portion of sublamina a and was more sparsely distributed. Whether determined by staining adjacent cells or by density vs. area calculations, coverage in the OPL approached 1 for each type, as did coverage in the IPL for the two types with narrow fields. PMID- 1613136 TI - Effects of prenatal ethanol exposure on the development of Bergmann glia and astrocytes in the rat cerebellum: an immunohistochemical study. AB - The consequences of prenatal ethanol exposure on the postnatal development of Bergmann glia and astrocytes in the rat cerebellum were investigated by using glial fibrillary acidic protein (GFAP) immunolabeling. Pregnant rats were either fed with an ethanol containing liquid diet (6.7% v/v) or pair-fed with an isocaloric diet throughout gestation. On postnatal day (PD) 15 and 22, parasagittal sections of the cerebellar vermis from female offspring were processed for GFAP immunohistochemistry to assess the development of Bergmann glia and astrocytes in lobules I, VII, and X and astrocytes in the central core of white matter. On PD 15, compared to control animals, ethanol exposed animals had fewer GFAP positive Bergmann glial fibers per unit length of molecular layer; a significantly greater percentage of morphologically immature Bergmann fibers; a significantly greater GFAP positive astrocytic area per unit area of internal granular layer and central white matter; and the astrocytic processes were wider and more closely packed. These glial changes were associated with significantly thicker external granular layer in all 3 lobules. However, no significant differences were seen between the ethanol exposed and control animals on PD 22, indicating "catch-up growth" in the ethanol exposed animals during the third postnatal week. These results suggest that prenatal ethanol exposure causes (1) delayed maturation of Bergmann glia, which in turn contributes to the delayed migration of granule cells; and (2) alterations in the normal postnatal development of astrocytes. PMID- 1613137 TI - Localization of mu class glutathione-S-transferase in the forebrains of neonatal and young rats: implications for astrocyte development. AB - The Yb (Mu class) isoform of glutathione-S-transferase has recently been localized in ependymal cells, subependymal cells, and astrocytes in the forebrains of rats 3 weeks to adult in age. It was not known, however, at what age Mu might first be observed during postnatal development and whether the first cells in which it was found would be immature astrocytes or some less differentiated glial precursor cell, if the latter were present in vivo. Tissue sections from the forebrains of neonatal to 16 day old rats were immunostained with antibodies against Mu. In neonates Mu was observed in vimentin-positive cells and their processes adjacent to the lateral ventricles, and in the corpus striatum. The colocalization with vimentin suggested that these were subependymal cells and radial glia. In the corpus striatum the radial glia, while still vimentin-positive, rapidly lost Mu from their radial cell processes, whereas the cell-bodies remained Mu-positive. During the first postnatal week the Mu positive, glial-fibrillary-acidic-protein (GFAP)-positive cell bodies of immature astrocytes appeared in the corpus striatum. The earliest Mu-positive cells in the immature white matter of the corpus callosum were vimentin-positive and had striking longitudinal processes that also were vimentin- and Mu-positive. Like the processes of radial glia, the longitudinal processes lost their Mu immunoreactivity, only later and more gradually. Mu-positive, GFAP-positive cells appeared later in the corpus callosum than in the corpus striatum.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613138 TI - Localization of Pi class glutathione-S-transferase in the forebrains of neonatal and young rats: evidence for separation of astrocytic and oligodendrocytic lineages. AB - The Yp isoform (Pi class) of glutathione-S-transferase has recently been localized in oligodendrocytes in the brains of mature rats. To examine at what postnatal age Pi first appears in oligodendrocytes or precursor cells, antibodies against Pi were used to immunostain tissue sections from the forebrains of neonatal rats and young rats up to 17 days of age. In the brains of neonates Pi immunofluorescence was observed in ovoid cells in the subependymal layer, and in ovoid cells and cells bearing short, thick processes in the corpus callosum and cingulum. These cells did not immunostain for vimentin. During the first postnatal week Pi-positive cells showed positive immunostaining for ganglioside GD3, which is characteristic of oligodendrocyte precursors, and process-bearing Pi-positive cells appeared in the cingulum and at the lateral borders of the corpus callosum in increasing numbers. During the second postnatal week the cytoplasm of Pi-positive cells became more compact, and the processes thinner, and the Pi-positive cells and their processes began to immunostain for 2',3' cyclic nucleotide-3'-phosphohydrolase, which is characteristic of immature and mature oligodendrocytes and myelin sheaths. By age 17 days Pi was observed in relatively mature oligodendrocytes. The observations suggest that Pi occurs in oligodendrocyte precursors, immature oligodendrocytes, and mature oligodendrocytes in the postnatal through 17 day old rat forebrain. In the accompanying paper (Cammer and Zhang, '92)--if references are permitted in the Abstract a different glutathione-S-transferase isoform, Yb (Mu class), was localized in cells of the astrocyte lineage, beginning in the forebrains of neonatal rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613139 TI - Spatial density and distribution of choline acetyltransferase immunoreactive cells in human, macaque, and baboon retinas. AB - Whole-mounted human, macaque, and baboon retinas were labelled with an antiserum to human choline acetyltransferase (ChAT), by the immunoperoxidase technique. Previous work in nonprimate species has shown that these cells correspond to the starburst amacrine cells. Labelled somata were disposed on either side of the inner plexiform layer, and their processes formed two narrow zones within it. In human retinas, the ratio of labelled somata in the ganglion cell layer (GCL) to those in the inner nuclear layer (nominal Sb/Sa ratio) was about 60/40 at all locations, similar to that found in nonprimate mammalian species. The density of labelled cells in the human GCL ranged from 1,000 to 1,150 mm-2 near the fovea to 300 to 400 mm-2 in the periphery. Labelling tended to be more erratic in macaque retinas. Nevertheless the Sb/Sa ratio was as high as 70/30 and spatial densities were similar to those of humans. The overlap factor in macaque retinas outside the nasal quadrant was about 10 at all retinal eccentricities, based upon dendritic-field sizes from a Golgi study. About each labelled soma there was a region 20 to 120 microns in diameter in which the probability of the occurrence of other labelled somata was lower than elsewhere. No such nonrandomness was found between labeled cells in the GCL and those in the amacrine cell layer. The packing factor was about 0.3 in well-labelled regions, independent of retinal position or spatial density. Published data on ChAT-labelled cells in rabbit and rat show a similar value. This invariance is consistent with the hypothesis that this nonrandomness is a residual consequence of somal contiguity at an early developmental stage. PMID- 1613140 TI - A quantitative light and electron microscopic analysis of taurine-like immunoreactivity in the dorsal horn of the rat spinal cord. AB - Taurine has been proposed as an inhibitory neurotransmitter or neuromodulator in the vertebrate central nervous system. Within the spinal cord, taurine has been shown to have a direct inhibitory effect on spinal neurons and to have a selective antinociceptive effect on chemically induced nociception. Although sufficient data exists to suggest that taurine plays a neurotransmitter or neuromodulatory role in the spinal cord, it is not known whether this amino acid is present in axon terminals nor if this amino acid has a unique pattern of distribution within spinal tissue. To address these questions a monoclonal antibody against taurine was employed to localize taurine-like immunoreactivity in the dorsal horn of the rat spinal cord by using both light and electron microscopic techniques. Taurine-like immunoreactivity was most dense and most prominent in laminae I and II of the dorsal horn. A moderate amount of immunoreactivity was also present in laminae VIII and IX and X while the remaining laminae were only lightly stained. In laminae I and II taurine-like immunostaining was evident within neuronal cell bodies, dendrites, myelinated and unmyelinated axons, axon terminals, and astrocytes and their processes. Cell counts of these two laminae indicated that approximately 30% of neuronal perikarya at the C2 level, 52% of neuronal perikarya at the T6 level, and 18% of neuronal perikarya at the L2 level of the cord exhibited taurine-like immunoreactivity. With preembedding diaminobenzidine staining, approximately 20% of the axons examined in laminae I and II were found to be immunoreactive for taurine. Using postembedding immunogold staining in combination with quantitative procedures, the highest densities of gold particles were found in axon terminals containing pleomorphic vesicles and forming symmetrical synapses (36.8 particles/micron2), in a subpopulation of myelinated axons (34.2 particles/micron2), in a subpopulation of neuronal dendrites (32.6 particles/micron2), and in capillary endothelial cells (39.8 particles/micron2). Moderate labeling occurred in astrocytes (20.9 particles/micron2) and neuronal perikarya (18.7 particles/micron2). The localization of taurine to presumptive inhibitory axon terminals provides anatomical support for the hypothesis that taurine may serve an inhibitory neurotransmitter role in the superficial dorsal horn of the spinal cord. On the other hand, its localization to astrocytes and endothelial cells within both the dorsal ventral horns implies that it serves other nonneuronal functions as well. PMID- 1613141 TI - Development and birthdates of vasoactive intestinal peptide immunoreactive neurons in the chick proventriculus. AB - To gain insight into the mechanisms regulating expression of transmitter phenotypes in the enteric nervous system, we have studied the development and birthdate of vasoactive intestinal peptide immunoreactive (VIP-IR) myenteric neurons in the chicken proventriculus (secretory portion of the avian stomach) by a combination of immunocytochemistry and radioautography. The appearance and numbers of VIP-IR neurons in whole mounts of the myenteric plexus from chick embryos and chickens were examined. We found that VIP-IR neurons first appeared at embryonic day (E) 5.5-6.5 in the distal part of the proventriculus. At E7.5, VIP-IR neurons were found singly, in pairs, or in small groups, which together with unlabeled cells formed primitive myenteric ganglia. VIP-IR fibers were found within the developing fiber tracts which connected the ganglia. The number of VIP IR neurons was found to be maximum in the E15.5 embryo and to decline to 68% of maximum in the 4 week old chicken. Birthdate studies were performed by application of either single pulses or cumulative doses of [3H]-thymidine to embryos between E3 and E14. Whole mounts of the myenteric plexus from the proventriculus of these embryos were immunostained for VIP at E10 or E17. The whole mounts were subsequently sectioned and processed for radioautography. We found that VIP-IR myenteric neurons were born between E3 and E10 with a peak at E7. Most cells underwent terminal division between E5 and E9. These data will be useful in determining the time and conditions when cells make decisions about transmitter phenotypes. PMID- 1613142 TI - Primary cutaneous large-cell anaplastic (Ki-1) lymphoma in a child. AB - During a 2-week period, a 9-year-old girl developed a tender, dark red, centrally ulcerated 3 cm tumor on her left thigh, associated with inguinal lymphadenopathy. Histologic and immunohistopathologic evaluation disclosed a Ki-1+ large-cell anaplastic lymphoma. The patient received multiagent chemotherapy followed by autologous bone marrow transplantation and is in her second remission. PMID- 1613143 TI - Treatment of reticulate acropigmentation of Kitamura with azelaic acid. An immunohistochemical and electron microscopic study. AB - No successful therapy has been reported for reticulate acropigmentation of Kitamura, which is an autosomal dominant dermatosis. We treated a patient with 20% azelaic acid ointment. Within several weeks the pigmentation was remarkably decreased and no side effects were observed. Histologic examination revealed an increased number of dopa-positive melanocytes. These cells reacted strongly to staining with antityrosinase antibody or antityrosinase-related protein antibody. Electron microscopic findings showed many melanosomes within melanocytes, keratinocytes, and melanophages. These findings suggest that the hyperpigmentation of reticulate acropigmentation of Kitamura is the result of an excess amount of melanin production caused by activation of melanocytes in the basal layer. PMID- 1613144 TI - Erythromelalgia in a patient with thrombotic thrombocytopenic purpura. AB - Erythromelalgia is characterized by paroxysmal burning pain and redness of the distal extremities; primary and secondary forms exist. Secondary erythromelalgia is most commonly associated with essential thrombocythemia and polycythemia vera, and the pathogenic mechanism is thought to be platelet aggregation. Thrombotic thrombocytopenic purpura is characterized by thrombocytopenia, microangiopathic anemia, renal failure, and fluctuating neurologic signs and symptoms. The pathogenic mechanism suggested for thrombotic thrombocytopenic purpura is diffuse platelet aggregation. We describe a female patient in whom thrombotic thrombocytopenic purpura was associated with erythromelalgia. This has not been previously reported. PMID- 1613145 TI - Orbital and palpebral paraffinoma. AB - Paraffinoma is a well-recognized complication of paraffin injection. We describe a 44-year-old man who had an ethmoidectomy for chronic sinusitis. A communicating fracture of the ethmoid bone into the orbit occurred intraoperatively. The nasal cavity was subsequently packed with gauze containing a petrolatum-based antibiotic ointment. Bilateral, periocular swelling developed 1 week later. Optical and electron microscopic studies revealed a paraffinoma. PMID- 1613146 TI - The development of B-cell lymphoma in a patient with psoriasis treated with cyclosporine. AB - A 67-year-old Nicaraguan man with a history of chronic, severe, recalcitrant psoriasis participated in a multicenter study investigating oral cyclosporine in the treatment of psoriasis. He received cyclosporine for approximately 8 months at doses of 5 mg/kg/day or less. Treatment with cyclosporine was eventually discontinued because of progressive nephrotoxicity. Approximately 7 months after the discontinuation of cyclosporine, the patient developed a mass in the left maxillary sinus extending to the orbit, the palate, and the infratemporal fossa. Pathologic and histochemical analysis of the mass revealed a B-cell lymphoma. The development of a benign lymphocytic infiltrate has been reported in a patient who received cyclosporine therapy for psoriasis; however, to the best of our knowledge, this is the first case in the United States of lymphoma developing in a patient who was treated with cyclosporine for a condition other than organ transplantation. PMID- 1613147 TI - Cutaneous metastasis from squamous cell carcinoma of the cervix. AB - Metastasis to the skin occurs rarely, regardless of the nature of the primary systemic neoplasm. Although carcinoma of the cervix is the fourth most common malignancy in women, cutaneous involvement originating from cervical cancer is particularly unusual, even in the terminal stages of disease. Only 22 cases, including this one, are clearly documented in the literature. The main sites of the cutaneous metastases in these cases were the abdominal wall or lower extremity. However, we describe a 41-year-old woman with cervical cancer who developed metastatic nodules on the upper back. The skin of the back is an uncommon location for metastasis from any malignant tumor, and when it occurs in women, it is generally associated with carcinoma of the breast or malignant melanoma. To the best of our knowledge, this is the first reported case of cervical carcinoma metastasis to this unlikely cutaneous site. PMID- 1613148 TI - CD1 (OKT6)-positive juvenile xanthogranuloma. OKT6 is not specific for Langerhans cell histiocytosis (histiocytosis X). AB - A 16-month-old boy had multiple papules on the face and trunk that were clinically and histologically typical of juvenile xanthogranulomas. Cells from the lesions reacted to staining for OKT6, but Birbeck granules were not identified ultrastructurally, which suggests that OKT6 is not a specific marker for Langerhans cell lineage. PMID- 1613149 TI - Palmoplantar keratoderma with sclerodactyly (Huriez syndrome). AB - A syndrome characterized by palmoplantar keratoderma, sclerodactyly, and skin cancer was first described in two families by Huriez et al. The pattern of inheritance was compatible with that of an autosomal dominant disorder. We report a patient with this condition and review the literature. PMID- 1613150 TI - Porphyria cutanea tarda in association with human immunodeficiency virus infection in a hemophiliac. AB - A case of porphyria cutanea tarda in a human immunodeficiency virus-infected patient with hemophilia is reported. Onset of skin manifestations of porphyria cutanea tarda coincided with deterioration of immune function. However, acquired immunodeficiency syndrome has not yet developed with a follow-up interval of 39 months. Treatment with zidovudine and topical steroids has resulted in significant improvement in the skin lesions. The clinical features of 11 other reported cases of human immunodeficiency virus-associated porphyria cutanea tarda are reviewed. The data suggest that a true association exists between human immunodeficiency virus infection and porphyria cutanea tarda, with onset of clinical signs of porphyria cutanea tarda coincident with declining immunologic function. PMID- 1613151 TI - Acquired symmetric lipomatosis of the soles. A plantar form of the Madelung Launois-Bensaude syndrome. AB - Benign symmetric acquired lipomatosis is a rare condition characterized by multiple, diffuse, subcutaneous collections of nonencapsulated mature adipose tissue. A thick and disfiguring deposit of fat is symmetrically distributed in the subcutaneous tissue of the neck, upper trunk and proximal portions of the upper extremities. The face, distal extremities, hands, and feet are characteristically spared. We describe a case in which only plantar involvement was present. PMID- 1613152 TI - Behcet's disease presenting as superior vena cava syndrome. AB - Behcet's disease is a multisystem disease with many systemic manifestations. Vascular thromboses with a predilection for the venous system are a well recognized complication. We report on a patient with superior vena cava syndrome and review different hypotheses regarding the underlying pathogenesis. PMID- 1613153 TI - Metastatic signet-ring cell melanoma in a patient with an unknown primary tumor. Histologic, immunohistochemical, and ultrastructural findings. AB - Signet-ring cell melanoma is a rare morphologic variant of malignant melanoma. We describe a 27-year-old man with widespread cutaneous and internal metastases of an unknown primary tumor. One skin biopsy specimen and a fine-needle aspirate showed polygonal tumor cells consistent with the diagnosis of metastatic melanoma, but a second skin biopsy specimen revealed neoplastic cells with a signet-ring cell appearance. Both specimens, however, yielded identical immunohistochemical findings. Tumor cells were positive for vimentin and S-100 protein and reacted with the melanoma markers HMB-45 and NKI-C3. Ultrastructural studies revealed abundant intermediate filaments in the cytoplasm of the signet ring cells. Based on these findings, a diagnosis of metastatic melanoma was made. In this report we describe the fourth case of metastatic signet-ring cell melanoma, and discuss how malignant melanoma may lead to metastases that have divergent morphologic appearances in the same patient. PMID- 1613154 TI - Relationship between steatocystoma multiplex and eruptive vellus hair cysts. AB - Steatocystoma multiplex (SM) and eruptive vellus hair cysts (EVHC) share a clinical resemblance, but have distinctive histologic features. We describe a patient who had both SM and EVHC lesions and discuss the relationship between the two diseases. We believe that SM and EVHC are within the spectrum of the same disease process and could both be termed multiple pilosebaceous cysts. PMID- 1613155 TI - Mid-dermal elastolysis with inflammation. AB - A 71-year-old white woman had finely wrinkled, erythematous patches of skin that met the clinical and histologic criteria for mid-dermal elastolysis. In addition to the loss of mid-dermal elastin described in previous cases, histopathologic examination revealed a superficial and deep perivascular inflammatory infiltrate of lymphocytes and plasma cells and interstitial collections of multinucleated giant cells containing phagocytized elastin. These results support a previously postulated inflammatory pathogenesis for mid-dermal elastolysis. PMID- 1613156 TI - Angiotensin II binding to tissues of the rainbow trout, Oncorhynchus mykiss, studied by autoradiography. AB - Tissue slices from seawater-adapted and freshwater-adapted rainbow trout, Oncorhynchus mykiss, were exposed to 125I-angiotensin II (1.01.10(-9) M) and binding sites located by light-microscopic autoradiography. Binding/uptake was significantly inhibited by excess (10(-5) M) unlabelled angiotensin II, suggesting specific binding/uptake of angiotensin II to the ventral and dorsal aorta (smooth muscle), urinary bladder (smooth muscle and epithelial lining), glomeruli and proximal tubules, the gill (lamellae and central filament), skin (epithelium), intestine and oesophagus (mucosal epithelium), liver, heart (ventricular myocytes), adrenocortical tissue and brain (cerebellum and medulla oblongata). The specific binding/uptake of angiotensin II to tissues of freshwater- and seawater-adapted animals were generally similar. However, binding/uptake by the proximal tubules was significantly higher in freshwater adapted trout than seawater-adapted trout. Specific binding/uptake of angiotensin II by the smooth muscle of the bladder was significantly higher in trout adapted to seawater than trout adapted to freshwater. PMID- 1613157 TI - Energy storage during reproductive diapause in the Drosophila melanogaster species group. AB - Temperate species of the Drosophila melanogaster group enter reproductive diapause for overwintering in response to short daylength. During the prediapause period they accumulate triacylglycerols, but not glycogen, as energy resources. The capacity for storing triacylglycerols differs between species, and appears to be closely correlated with diapause and cold-hardiness; cool-temperate species, such as those of the auraria species complex, which enter a deep diapause and are highly cold-hardy, accumulate larger quantities of triacylglycerols than warm temperate species, such as D. rufa and D. lutescens, which enter a weak diapause and are less cold-hardy. Among the cool-temperate species, D. subauraria occurs at a higher latitude and has the greatest capacity for accumulating triacylglycerols. A subtropical species, D. takahashii, which has no diapause in nature and is not cold-hardy, is unable to store the same quantities of triacylglycerols as temperate species. PMID- 1613158 TI - Caecal function provides the energy of fermentation without liberating heat in the poikilothermic mammal, Heterocephalus glaber. AB - This paper presents the first report of a mammalian internal organ with a lower temperature than its abdominal surrounds. Heterocephalus glaber, the naked mole rat, is a poikilothermic mammal that leads a strictly subterranean existence and consumes a high proportion of fibre in its diet. The fermentation chamber in these animals appears to absorb rather than generate heat and the temperature in it was consistently 1.2 +/- 0.5 degrees C (n = 17) lower than rectal temperature. A caecum with a lower temperature than its abdominal surrounds provides an internal heat sink which could be advantageous for metabolic heat dissipation in the plugged humid burrows in which the naked mole-rat permanently resides. PMID- 1613159 TI - Mechanisms of Cl- uptake through brush border membranes isolated from the posterior intestine of the freshwater trout, Oncorhynchus mykiss, R. AB - This paper presents a study of the mechanisms of Cl- transport through the brush border membranes of the posterior part of the intestine in the freshwater trout, Oncorhynchus mykiss. The mechanisms for Cl- transport in the posterior intestine are distinct from those in the middle intestine; an inwardly directed pH gradient stimulates Cl- uptake by brush border membrane vesicles, indicating a Cl-/OH- exchange. A pH-regulated Cl- conductance is present, which is not activated at normal intracellular pH. Cl- uptake is stimulated by an outwardly directed HCO3- gradient revealing the presence of a Cl-/HCO3- exchange but, conversely, Cl- is not exchanged against SO4(2-). In addition, carbonic anhydrase activities have been detected in both the intracellular and extracellular leaflets of the brush border membranes which favour the establishment of a bicarbonate gradient. A model of Cl- transport mechanisms through the brush-border membranes of the posterior intestine of the freshwater trout is proposed. PMID- 1613160 TI - Effect of salmon gonadotropic hormone on sex steroids in male rainbow trout: plasma levels and testicular secretion in vitro. AB - Male rainbow trout were treated with salmon gonadotropic hormone (GTH) at different stages of the circannual reproductive cycle; spawning fish were also treated with an antiserum against salmon GTH. Injection of GTH led to a several fold increase of plasma sex steroid levels during spermatogenesis and in the spawning season but was without effect at early stages of testicular development. GTH neutralization during the spawning season was followed by a several-fold decrease of plasma sex steroid levels. During spermatogenesis and in the spawning season, both treatment regimes resulted in an increased sensitivity of testicular explants in response to a subsequent stimulation of steroid secretion in vitro. This up-regulatory response may facilitate and maintain the high sex steroid plasma levels observed during the spawning season. It may also be necessary to allow for concomitant peak values of plasma GTH and sex steroids in the spawning season, a situation difficult to understand within the negative feedback concept. The adaptive capacities of the testicular steroidogenic system indicate that it is not only an effector site for GTH but also an active part of the endocrine system controling reproduction. PMID- 1613161 TI - Studies on the fish gill microclimate. AB - An isolated and perfused fish gill filament preparation has been developed to facilitate investigations on the fish gill microclimate. Measurements have been made of the concentration of sodium at the lamellar surface and in the mixed-exit water, and of the maximum interlamellar velocity. When the external water has a sodium concentration of 0.10 mmol.l-1, water at the gill surface has a mean sodium concentration of 0.146 mmol.l-1. Mixed-exit water, 50 microns behind the perfused filament, has a mean sodium concentration of 0.118 mmol.l-1. When the water flowing over the filament has a maximum velocity of 18 cm.s-1, the maximum velocity between secondary lamellae is 1.5 cm.s-1. These measurements have been used to support the development of a velocity-modified diffusion model which describes ion movement in the interlamellar space. The analysis and observations on the preparation suggest that substantial unstirred layers do not exist at the lamellar surfaces in this preparation. Simple diffusion to and from the tissue surfaces, in conjunction with parabolic velocity profiles within the interlamellar spaces adequately explain net sodium movements. PMID- 1613162 TI - Analytical and experimental studies on the relationship between Na+, K+, and water uptake during volume increases associated with Fundulus oocyte maturation in vitro. AB - Oocytes of marine and estuarine teleosts often undergo pronounced volume increases during the maturation phase of development that precedes ovulation and fertilization. To examine the physiological correlates of these volume increases, prematuration follicles of the saltmarsh teleost, Fundulus heteroclitus, were cultured in vitro with a maturation-inducing steroid (17 alpha-hydroxy-20 beta dihydroprogesterone). Mean follicle volume rose significantly (75%) during a 40-h incubation period. Similar to the situation previously found in vivo, uptake of water by the maturing follicle was responsible for this volume increase in vitro, with the water content increasing from 62% to 78% of the total follicle mass. The follicle contents of two probable osmotic effectors--Na+ and K(+)--also rose, the increase in K+ being twice that of Na+. The influx of K+ even exceeded water uptake, resulting in a net increase in the concentration of this cation. It thus appears that the influx of these cations, in particular K+, is a major cause of the uptake of osmotically obligated water and subsequent volume increase experienced by maturing F. heteroclitus follicles. In a search for operant mechanisms, it was found that follicle hydration, but not maturation, was strictly dependent on external K+ in a concentration-dependent manner. The mechanism by which K+ accumulates in the follicle was insensitive to ouabain, so that a typical Na+, K(+)-ATPase mechanism does not appear to be involved. The ability of external K+ to promote follicle hydration was gradually lost during the maturation process as the oocyte dissociated from the surrounding granulosa cells in preparation for ovulation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613163 TI - Time-dependent thresholds for torpor initiation in the rufous hummingbird (Selasphorus rufus). AB - Three models for torpor initiation were tested in rufous hummingbirds (Selasphorus rufus) during moult, when these birds appear to avoid the use of torpor. In model 1, the level of energy reserves at which torpor is initiated (the "threshold") remains constant throughout the night. In model 2, the threshold declines throughout the night, at a constant rate equivalent to the rate at which energy reserves are depleted during torpor. In model 3, the threshold declines at a rate equivalent to the rate of energy reserve depletion during torpor for most of the night, but at a higher rate (corresponding to the rate of energy expenditure during normothermia) during the final 2 h of the night, when these birds are usually normothermic. Model 1 predicts the most frequent and longest bouts of torpor, whereas model 3 predicts the fewest and shortest bouts. To determine the thresholds for each of 12 birds, food supply was manipulated to induce entry into torpor at different times on successive nights. Threshold slopes matched the predictions of model 3 most closely. Calculations comparing observed incidence of torpor with the predictions of model 1 show that the actual, time-dependent threshold for torpor initiation resulted in a 72% reduction in the number of torpor bouts compared with the number of torpor bouts that should have been initiated by a constant threshold. The advantage of a time dependent threshold is that, although torpor is initiated when needed to prevent energy reserves from falling below a critical level, the amount of time spent in torpor can be minimized.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613164 TI - Myocardial oxygen consumption and mechanical efficiency of a perfused dogfish heart preparation. AB - Oxygen consumption of an in-pericardium heart preparation from the spiny dogfish (Squalus acanthias) was linearly related to cardiac power output. Basal oxygen consumption, predicted from the regression, was 0.127 microliters.s-1.g ventricle mass-1 and increased by 0.189 microliters.s-1.g ventricle mass-1 per milliwatt of power generated. From the relationship between cardiac power output and mechanical efficiency, mechanical efficiency was predicted to increase with cardiac power output to a maximum of 21%. Mechanical efficiency was measured during volume loading and pressure loading at two power outputs (50% and 72% of maximum power output). At 50% of maximum power output, mechanical efficiency increased significantly by 2.87%, from 11.9 +/- 0.3% to 14.8 +/- 0.5% (n = 7), when flow was halved and output pressure doubled to achieve the same power output. Similarly, at 72% of maximum power output, mechanical efficiency increased from 14.74 +/- 0.92% to 17.61 +/- 0.84% (n = 6) when flow was halved and output pressure doubled to generate the same higher level of power output. The increased mechanical efficiency at higher output pressures is believed to result from cardiac myocytes working within a length range where they are able to generate the most tension during contraction and are most efficient. We speculate that the loss of mechanical efficiency associated with large changes in sarcomere length, when stroke volume is large, is a driving force behind the use of frequency as the principal means of increasing cardiac output as observed in more active fishes, birds and mammals. PMID- 1613165 TI - De novo purine biosynthesis in the crustacean Artemia: influence of salinity and geographical origin. AB - In vivo studies of the incorporation of [U-14C]glycine into purine nucleotides have established the de novo pathway for purine biosynthesis in Artemia sp. during the early period of larval development. This pathway can be modified by the salt concentration of the incubation media. In addition, Artemia of different geographical origins may differ with respect to the detection, functionality and variability of this metabolical pathway. PMID- 1613166 TI - Flight of the honeybee. V. Drag and lift coefficients of the bee's body; implications for flight dynamics. AB - Drag forces and lift forces acting on honeybee trunks were measured by using specially built sensitive mechanical balances. Measurements were made on prepared bodies in 'good' and in 'bad' flight position, with and without legs, at velocities between 0.5 and 5 m.s-1 (Reynolds numbers between 4.10(2) and 4.10(3)) and at angles of attack between -20 degrees and +20 degrees. From the forces drag coefficients and lift coefficients were calculated. The drag coefficient measured with a zero angle of attack was 0.45 at 3 less than or equal to v less than or equal to 5 m.s-1, 0.6 at 2 m.s-1, 0.9 at 1 m.s-1 and 1.35 at 0.5 m.s-1, thus demonstrating a pronounced effect of Reynolds number on drag. These values are about 2 times lower (better) than those of a "drag disc" with the same diameter and attacked at the same velocity. The drag coefficient (related to constant minimal frontal area) was minimal at zero angle of attack, rising symmetrically to larger (+) and smaller (-) angles of attack in a non-linear fashion. The absolute value is higher and the rise is steeper at lower speeds or Reynolds numbers, but the incremental factors are independent of Reynolds number. For example, the drag coefficient is 1.44 +/- 0.05 times higher at an angle of attack of 20 degrees than at one of 0 degrees. On a double-logarithmic scale the slope of the drag versus Reynolds number plot was 1.5: with decreasing Reynolds number the relationship between drag and velocity changes from quadratic (Newton's law) to linear (viscous flow). Trunk drag was not systematically increased by the legs at any velocity or Reynolds number or any angle of attack. The legs appear to shape the trunk "aerodynamically", to form a relatively low-drag trunk-leg system. The body is able to generate dynamic lift. Highly significant positive linear correlations between lift coefficient and angle of attack were determined for the trunk-leg system in the typical flight position. Lift coefficient was +0.05 at zero angle of attack (possibly attained during very fast flight), +0.1 at 5 degrees (attained during fast flight), +0.25 at +20 degrees (attained during slow flight) and +0.55 at 45 degrees (attained whilst changing over to hovering). Average slope delta cL/delta alpha was 0.66 +/- 0.07, and average profile efficiency was 0.10. Non-wing lift contribution due to body form and banking only accounts for a few percent of body weight during fast flight.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613167 TI - Warm-up rates during arousal from torpor in heterothermic mammals: physiological correlates and a comparison with heterothermic insects. AB - This study examines the relationship between warm-up rate, body mass, metabolic rate, thermal conductance and normothermic body temperature in heterothermic mammals during arousal from torpor. Predictions based on the assumption that the energetic cost of arousal has been minimised are tested using data for 35 species. The observation that across-species warm-up rate correlates negatively with body mass is confirmed using a comparative technique which removes confounding effects due to the non-independence of species data due to shared common ancestry. Mean warm-up rate during arousal correlates negatively with basal metabolic rate and positively with the temperature difference through which the animal warms, having controlled for other factors. These results suggest that selection has operated to minimise the overall energetic cost of warm-up. In contrast, peak warm-up rate during arousal correlates positively with peak metabolic rate during arousal, and negatively with thermal conductance, when body mass has been taken into account. These results suggest that peak warm-up rate is more sensitive to the fundamental processes of heat generation and loss. Although heterothermic marsupials have lower normothermic body temperatures and basal metabolic rates, marsupials and heterothermic eutherian mammals do not differ systematically in warm-up rate. Pre-flight warm-up rates in one group of endothermic insects, the bees, are significantly higher than predictions based on rates of arousal of a mammal of the same body mass. PMID- 1613169 TI - Continuing nursing education. PMID- 1613168 TI - Ready, set, certify: getting ready for the new certification examination. PMID- 1613170 TI - Milk yield responses to sequential treatments with recombinant bovine somatotropin and frequent milking in lactating goats. AB - Lactating goats routinely milked twice daily were used. Starting at peak lactation, two groups of five goats were milked three times daily unilaterally (right gland) for 6 weeks, then one group received recombinant bovine somatotrophin (BST) by daily injection for 6 weeks, and finally both groups were returned to unilateral thrice-daily milking (left gland) for 6 weeks. Thrice daily milking increased milk yield significantly by 10.4%. As thrice-daily milking finished and BST treatment began there was a small (2.7%) but significant increase in whole-udder milk yield in the treated goats and a decline in the control goats; throughout the BST treatment period treated goats produced 14.3% more milk than controls. The effect of BST was the same in glands previously milked thrice daily as in those previously milked twice daily. Milk yield declined as BST treatment finished, but this decline was less in the glands that then began thrice-daily milking. The effect of milking frequency was similar in this period to that obtained earlier in the experiment, and was not different between goats that had previously received BST and those that had not. The results are discussed in relation to the proposed modes of action of BST and frequent milking, and possible interactions between the two. PMID- 1613171 TI - Capture immunoassay for the diagnosis of bovine mastitis using a monoclonal antibody to polymorphonuclear granulocytes. AB - A direct capture enzyme-linked immunosorbent assay (ELISA) was developed to measure elevated polymorphonuclear granulocyte (PMN) antigens using horseradish peroxidase (EC 1.11.1.7) conjugated rabbit polyclonal anti-PMN antisera and a monoclonal antibody specific for PMN cells. Optical densities obtained in the ELISA were used to predict the cell counts of milk samples. Predicted counts were not significantly different from actual somatic cell counts (SCC). In a total of 156 bovine milk samples the correlation coefficient between somatic cell counting, taking greater than 500,000 cells/ml as being indicative of mastitis, and the assay was 0.94, yielding an assay sensitivity of 95.2% and a specificity of 97.3%. In further trials the ELISA could detect elevated PMN antigens in milk with SCC as low as 100,000 cells/ml. The results indicate that the monoclonal antibody based direct ELISA has excellent potential in the detection and determination of bovine mastitis. PMID- 1613172 TI - Effect of insulin in conjunction with glucose, amino acids and potassium on net metabolism of glucose and amino acids in the goat mammary gland. AB - The hyperinsulinaemic euglycaemic insulin clamp technique was used to study the effect of insulin on the arterio-venous concentration differences of glucose and amino acids across the mammary gland in dairy goats. Insulin was given in conjunction with K to prevent insulin hypokalaemia. Appropriate amino acid infusion was used to blunt insulin-induced hypoaminoacidaemia or to create hyperaminoacidaemia and maintain this state under insulin treatment. Hyperaminoacidaemia alone only stimulated mammary leucine uptake but did not significantly modify the net metabolism of other amino acids and glucose. Insulin infusion at physiological level in conjunction with glucose, KCl-NaCl and amino acids failed to alter mammary uptake of glucose and essential amino acids; occasional increase in arginine extraction and decrease in tyrosine extraction were exceptions. Thus these new experimental conditions did not reveal any galactopoietic effect of insulin. PMID- 1613173 TI - B-mode ultrasonography of mammary glands of cows, goats and sheep during alpha- and beta-adrenergic agonist and oxytocin administration. AB - Teat and gland cistern of the mammary glands of five dairy cows, five goats and five sheep were scanned in a water bath during alpha- and beta-adrenergic agonist and oxytocin administration. A 5 MHz linear array scanner was used to create vertical cut pictures with the scan plane longitudinally through the teat channel. The i.v. injection of the alpha-adrenergic agonist phenylephrine (30 micrograms/kg) induced diminution of the section area through teat and gland cistern by 38 +/- 17% on average within 1 min in all three species. In contrast, the i.v. injection of the beta-adrenergic agonist isoproterenol (1 microgram/kg) did not change the cisternal areas. The i.v. injection of oxytocin (2.0 x 10(-3) i.u./kg) elicited an enlargement of teat and gland cistern area by 48 +/- 12% on average. Ultrasonography proved to be a valuable system for visualizing changes of the cisternal volume. Smooth muscle contractions in response to phenylephrine administration are thought to cause area reduction, whereas an expected smooth muscle relaxation after injection of isoproterenol could not be observed by ultrasonography. Milk ejection as induced by oxytocin administration caused dramatic enlargement of the cistern area in all three species. PMID- 1613174 TI - Calcium, phosphate and citrate in human milk at initiation of lactation. AB - The onset of copious milk secretion (lactogenesis II) in women occurs between 1 and 3 d after birth, and during this period the composition of breast milk changes. During the first 5 d of lactation we measured the concentrations of total, diffusible and ionized Ca (Catot, Cad, Ca2+), diffusible phosphate (Pid), diffusible citrate (Citd) and lactose in the breast milk. On day 1 after birth the concentrations (mean +/- SEM) were Catot, 5.71 +/- 0.30 mM; Cad, 2.66 +/- 0.19 mM; Ca2+, 2.90 +/- 0.18 mM; Pid, 0.26 +/- 0.16 mM; Citd, 0.25 +/- 0.03 mM and lactose, 76 +/- 11 mM. Between day 1 and day 4 the concentration of Catot increased 1.7-fold to 9.56 +/- 0.39 mM, Cad increased 1.8-fold to 4.75 +/- 0.26 mM, Ca2+ decreased by 20% to 2.33 +/- 0.13 mM, Pid increased 6.6-fold to 1.69 +/- 0.11 mM, Citd increased 20-fold to 5.06 +/- 0.21 mM, and lactose increased 2.3 fold to 173 +/- 4 mM. A high correlation has been found between [Cad] and [Citd] in the milk of both ruminant and non-ruminant species, which show a wide range in concentrations of [Cad] and [Citd], and the data fit a simple physicochemical model of ion equilibria in the aqueous phase of milk. The results of the present study confirm the relationship between [Cad] and [Citd] in human milk, even during lactogenesis II when the composition of the milk is changing very rapidly. PMID- 1613175 TI - Comparison of whole saliva flow rates and mucin concentrations in healthy Caucasian young and aged adults. AB - Unstimulated and chewing-stimulated whole saliva samples were obtained from 42 healthy Caucasians; 21 were between 18 and 35 years of age, and 21 between 65 and 83 years of age. The unstimulated salivary flow rate was significantly lower in the aged group, but the stimulated flow rate was significantly higher in the aged than in the young group. Both groups showed significantly increased flow during salivary stimulation. MG1 and MG2 concentrations in unstimulated and stimulated saliva samples were significantly lower in the aged group. There were no significant correlations between salivary flow rates and MG1 and MG2 concentrations. PMID- 1613176 TI - A comparison of jaw muscle cross-sections of long-face and normal adults. AB - Long-face subjects have smaller maximum molar bite forces than do normal individuals. This has been attributed both to differences in moment arms and size of the jaw muscles. In this study, a comparison was made between the mid-belly cross-sectional areas of the jaw muscles of 13 long-face and 35 normal adults by means of serial MRI scans. The subjects were selected on the basis of anterior lower face height as a percentage of anterior total face height. These and other cephalometric variables were measured from lateral radiographs. In the long-face group, the cross-sectional areas of the masseter, medial pterygoid, and anterior temporal muscles were, respectively, 30%, 22%, and 15% smaller than in the control group. By a discriminant analysis and a multivariate analysis of variance, these differences were found to be significant (p less than 0.001). The findings of this study hint that differences in the sizes of the jaw muscles of long-face and normal subjects might explain, in part, the observed differences in maximum molar bite force. PMID- 1613177 TI - A fluoride dose-response evaluation in an anticaries clinical trial. AB - This study evaluated the dose-response relationship between four increasing levels of fluoride from 1000 to 2500 ppm F as sodium monofluorophosphate (MFP) and three-year dental caries increments, as measured by DMFS, DMFT, and DFS-A on 4424 schoolchildren. The results indicated consistent linear decreases in all three dental indices as the dose level increased to 2500 ppm F MFP, with slopes (average reductions) of 0.32 in DMFS for an increase of 1000 ppm F, 0.13 in DMFT, and 0.17 in DFS-A when all children were evaluated, p less than 0.03 for each index. For children 11 years and older at baseline, the slopes quadrupled, p less than 0.01 for each index. Age and baseline DMFS were shown to be the most important covariates to control for in the statistical models. No differences in adverse reactions, or other safety problems, were observed at the different dose levels. PMID- 1613178 TI - Alterations in rat condylar cartilage following discectomy. AB - The purpose of this study was to examine the effect of unilateral extirpation of the articular disc of the temporomandibular joint on selected metabolic and compositional characteristics of the condylar cartilage. Unilateral discectomy was performed in one group of growing (28-day-old) rats, while another group received only unilateral arthrotomy. The effect of the discectomy procedure was assessed by comparison of ratios of the operated to unoperated sides in the discectomy and arthrotomy groups. Total uronic acid content (micrograms/mg dry tissue wt) of the condylar cartilage and [35S]-sulfate incorporation (dpm/micrograms uronic acid) into the condylar cartilage were decreased in discectomy-group animals at nine, 16, and 28 days following surgery, while hydration of the cartilage was increased in discectomy animals at both 16 and 28 days post-surgery. Wet and dry tissue weights of the cartilage were dramatically increased in discectomy-group animals at all post-operative intervals. These metabolic and compositional changes were accompanied by pronounced structural alterations in the cartilage, including chondrocyte clustering and tears parallel to the articular surface. With the exception of [35S]-sulfate incorporation, the changes demonstrated in the condylar cartilage following discectomy were similar to early osteoarthritic alterations reported in limb articular cartilage following partial meniscectomy or cruciate ligament resection. PMID- 1613179 TI - Chlorhexidine effects on membrane lipid domains of human buccal epithelial cells. AB - The effect of chlorhexidine gluconate on the adherence of Candida albicans to human buccal epithelial cells (BEC) and drug-induced alterations in BEC membrane lipid packing order were examined. Treatment of BEC with attached yeasts with 0.1 and 0.2% chlorhexidine resulted in significant yeast detachment after 90 and 60 min, respectively. Following pre-treatment of BEC with greater than 0.1% chlorhexidine, yeast adherence was inhibited by greater than 80%. In parallel experiments, the fluorescence anisotropy of BEC labeled with fluorescent membrane probes--diphenylhexatriene (DPH) and trimethylammonium DPH--was assessed following exposure to chlorhexidine. The fluorescence anisotropy decreased with increasing concentrations of chlorhexidine, which indicated that the drug decreased epithelial-cell membrane-lipid packing order. Chlorhexidine concentrations that altered epithelial-cell membrane-lipid packing order, particularly in superficial regions, were similar to those drug concentrations required for detachment of adherent yeasts. Similar results were obtained with a second antifungal, nystatin A. While the effects of chlorhexidine on the buccal cell membrane-lipid packing order were not reversed by multiple washings, the opposite situation occurred with nystatin A. The results suggest that chlorhexidine-induced alterations of BEC membrane-lipid order may be involved in the antifungal actions of the drug. PMID- 1613180 TI - Changes in the microvasculature after mechanical pressure on the hamster cheek pouch. AB - The reaction of the microvasculature in the periodontal ligament to mechanical pressure is considered a very important phenomenon with respect to the biological background to orthodontic tooth movement. For clarification of the microvascular reaction to mechanical pressure, an experimental model that incorporated a hamster cheek pouch was established. This in vivo model solves some of the problems of other experimental models of the microvasculature of the periodontal ligament. Blood plasma permeation in this model was examined by means of a blue dye (pontamine sky blue), and histological observation was performed by light and transmission electron microscopy. Increased vascular permeability was observed within 30 min after removal of the mechanical stimulation. The threshold weight resulting in dye leakage was between 1 and 5 g applied for 60 min. From the histological observations, some large gaps between the endothelial cells in venules were found, while most basement membranes remained undisturbed. These observations suggest that the plasma leakage was due to mild traumatic injury to the endothelial cells. Both leukocytes and platelets were observed in the gaps between the endothelial cells in the venule. These types of microvascular reactions to mechanical pressure could initiate tissue changes in the periodontal ligament during orthodontic tooth movement. PMID- 1613181 TI - Fluoride sorption characteristics of different grades of bone charcoal, based on batch tests. AB - Although bone charcoal (char) has been recommended for use in the de-fluoridation of drinking water in developing countries, parameters relating to fluoride (F) sorption characteristics by grade or type of bone char are unclear. Based on batch tests, the rate and capacity of F uptake were highest with black grade, followed by grey grade and lowest with white grade. Twenty-four-hour contact-time F sorption isotherms indicated saturation at capacities of 11.4 mg F per g of black grade, 2.4 mg F per g of grey grade, and less than 0.3 mg F per g of white grade bone char. Additional investigations showed that F-removal efficiency of black grade char decreased steadily with increasing F concentration. Its initial sorption kinetics were dependent on particle size, and the highest sorption rate was observed with particle sizes below 0.42 mm. For maximum sorption rate, the critical mixing time was between five and 15 min. The presence of chloride anions and elevated temperatures increased the rate of F uptake by black bone-char. The pH of distilled water following contact with bone char rose to 11.5 for white bone-char, 8.3 for grey bone-char, and 7.8 for black bone-char. The effects of processing temperature on the availability of intra- and extra-apatitic F-binding sites, levels of oxides of calcium and magnesium, and the carbon content were viewed as possible causes of observed variations. These findings suggest that the black grade of bone char was the most efficacious for use in partial de fluoridation of drinking water. PMID- 1613182 TI - Iron in the enameloid of perciform fish. AB - It is known that a high concentration of iron is deposited in the enameloid of some teleostean fish. Previously, Suga et al. (1989) pointed out that the iron concentration in the enameloid is related to the phylogeny of fish rather than to the feeding habits, according to the results of quantitative iron analyses on the teeth of marine teleost fish of the Tetraodontiformes. In the present study, in order for the previous idea to be verified, quantitative iron analysis was made with an electron microprobe on the enameloid of fish belonging to the Perciformes, which is the largest group of teleostean fish in the world and consists of both marine and freshwater species. The enameloid of all the fish examined (57 species) contained high iron concentrations ranging from 0.2% to 10.2% at the surface or middle layer, whereas that of an advanced suborder, Tetraodontoidei, of the Tetraodontiformes was very low in iron, at a level which could not be discriminated from the background value of the emission intensity. The distribution pattern of iron in the enameloid was classified into at least two types, namely, type A, in which a high iron concentration was observed mainly in the surface layer, and type B, in which iron was deposited throughout the entire layer, although there were differences in concentration. There were some differences in the concentration and distribution of iron in the enameloid for the families; for example, those of the Scaridae had a type A distribution, with about 0.2% iron only at the surface layer, whereas those of the Cichlidae, Centrarchidae, and Acanthuridae, which showed a type B distribution, contained iron ranging from 2.9% to 10.5% at the surface or middle layer of enameloid. Such differences seemed to be associated with the difference in timing of the commencement of the iron deposition into the developing enameloid, which is probably related to the phylogeny of fish. There was no evidence to support the idea that the iron concentration in the enameloid is associated with the feeding habits of fish, as proposed by previous investigators. PMID- 1613183 TI - A new method for promoting adhesion between precious metal alloys and dental adhesives. AB - A new, simple method of modifying the adherend metal surface by a liquid Ga-Sn alloy (Adlloy) was applied to dental precious and base-metal alloys for adhesion with 4-META adhesive resin. Adhesions of 4-META resin to three other surface states--as-polished, oxidized at high temperature, and electroplated tin--were also performed for comparison with the adhesion on Adlloy-modified surfaces. Bond strength measurements were made, and the durability against water at the adhering interface was evaluated. The Adlloy-modified gold alloys (Type IV and 14 K) and silver-based alloys (Ag-Pd and Ag-Cu) showed not only high bond strengths but also excellent water durability at the adhesion interface. Surface modification by Adlloy, however, did not affect adhesion to Ag-In-Zn and base-metal (SUS, Co Cr, and Ni-Cr) alloys. Adhesion to the tin-electroplated specimens was comparable with that to the Adlloy-modified specimens. PMID- 1613184 TI - ESCA study on dental alloy surfaces modified by Ga-Sn alloy. AB - A new, simple surface modification method for adherend metals has been developed. It gives high bond strength and superior water durability to dental precious metal alloys bonded with 4-META/MMA-TBB resin. However, there was no effect on the bonding of Ag-In-Zn alloy and base-metal alloys. In the present study, the alloy surfaces modified by the new method were analyzed by ESCA and SEM for determination of details of the modification effect. A new alloying layer containing Ga and Sn was formed on the precious-metal alloys. The main factor for excellent adhesion to be achieved was the formation of a very thin layer of Ga2O3 and SnO2, less than 1-2nm thick, on the alloy surface. A thicker modified layer, as formed on the Ag-In-Zn and Ni-Cr alloys, led to low bonding ability. PMID- 1613185 TI - Effects of external bleaching on indentation and abrasion characteristics of human enamel in vitro. AB - The application of home-bleaching procedures as a means of lightening multiple teeth has become increasingly popular. Very few studies, however, have determined the effect of this treatment upon dental hard tissues. This in vitro study evaluated the effects of a 10% carbamide peroxide gel on the apparent fracture toughness, hardness, and abrasion characteristics of human enamel. The apparent fracture toughness of enamel was reduced by about 30% after bleaching for a period of 12 hours with no significant change in surface hardness. Enamel treated with the bleaching gels also exhibited a small but significant decrease in abrasion resistance. This behavior was most likely due to an alteration of the organic matrix of enamel under the chemical action of hydrogen peroxide. Further investigation of the clinical significance of this process is needed. PMID- 1613186 TI - Dentistry for the year 2000--a Japanese dental industry's perspective. PMID- 1613187 TI - Monitoring of central venous oxygen saturation versus mixed venous oxygen saturation in critically ill patients. AB - Continuous monitoring of mixed venous (SvO2) and central venous (ScO2) oxygen saturation was compared in 7 critically-ill patients (Apache II score: 19 +/- 2.1) to determine whether or not information derived from ScO2 were reliable in clinical practice. Patients were catheterized with both a pulmonary artery (PA) and a central venous (CV) catheter, each of them mounted with fiberoptic sensors (Opticath PA Catheter P7110 and Opticath CV Catheter U440, Abbott). A total of 580 comparative measurements were obtained during periods without and with therapeutic interventions (drug-titration, bronchial suction, use of PEEP, changes in FiO2 ...). The systematic error between the 2 measurement techniques was 0.6% and 0.3% in periods with and without therapeutic interventions, respectively. The variability between the 2 techniques was 10% for both periods. Differences between the values were greater than or equal to 5% in 49% of values during periods of stability and in 50% of values during periods with therapeutic interventions. There were poor correlations between the values during periods without (r = 0.48) and with therapeutic interventions (r = 0.62). Better, but still less than ideal, correlations were obtained with changes in SvO2 and ScO2 during periods without (r = 0.70) and with therapeutic interventions (r = 0.77). Although there is a need to develop a simple technique to monitor mixed venous oxygen saturation, the present study indicates that ScO2 monitoring was not reliable in the study patients. PMID- 1613188 TI - The influence of nutrition on neonatal respiratory muscle function. AB - Advances in neonatal intensive care have resulted in increasing survival of very small babies, who often require prolonged periods of mechanical ventilation. These babies have limited nutritional reserves, and are difficult to feed by either parenteral or enteral routes. This review article discusses the interaction between undernutrition and respiratory muscle function in the critically ill preterm baby. PMID- 1613189 TI - Cardiopulmonary resuscitation in paediatric intensive care patients. AB - To identify the success of cardiopulmonary resuscitation in the paediatric ICU patient we undertook a retrospective study in an 11-bed medical and a 14-bed surgical paediatric ICU over a 32-month period. Thirty-four patients suffered an arrest in the ICU. Only 4 patients could be resuscitated successfully; 1 died after 24 h. Of the 3 long-term survivors 1 suffered from severe neurologic sequelae. All patients were in CCS classes III or IV. All but 3 patients had PSI scores greater than 8. The decision to resuscitate or to withhold therapy in individual patients who are deteriorating in the course of a critical, preceding illness should not be based on the risk index of these scoring systems. Both medical and ethical considerations should be guidelines in the process of decision-making. PMID- 1613190 TI - Effect of ventilation with positive end-expiratory pressure on the development of lung damage in experimental acid aspiration pneumonia in the rabbit. AB - Sixteen anaesthetized rabbits were subjected to tracheostomy and lung damage produced by the instillation of 4.5 ml/kg hydrochloric acid (pH 1.5) into the trachea. Half of the animals were ventilated with a positive end-expiratory pressure (PEEP) of 3 cmH2O and half with a PEEP of 10 cmH2O for 5 h, the mean airway pressure being kept at 12 cmH2O by adjustment of the end-inspiratory pause time. Pressure-volume curves were recorded every hour. Although the arterial PO2 values and compliance above the inflection point on the pressure-volume curve were greater in the group submitted to 10 cmH2O PEEP, there were no significant differences between the groups in terms of survival and histological findings. PMID- 1613192 TI - ARDS following acute lithium carbonate intoxication. AB - Lithium is a two-edged sword; it is on the one hand a unique drug with invaluable psychoactive potential and on the other a drug which can cause multisystem toxicity and even death. We present a case of severe lithium intoxication with multiple organ involvement. Our patient developed the adult respiratory distress syndrome (ARDS), nephrogenic diabetes insipidus (DI), distinctive neurological abnormalities, and hyperglycemia. We believe that this is a case of ARDS due to lithium toxicity in which elevated left atrial pressures were excluded by right heart catheterization and suggest a causal relationship between lithium and ARDS. PMID- 1613191 TI - Pulmonary and haemodynamic effects of extracorporeal circulation in the cat and the beneficial effects of prostacyclin. AB - Side-effects of a veno-venous extracorporeal system and possible beneficial effects of prostacyclin (epoprostenol) are analyzed on the cat. Three groups were studied; one control group without extracorporeal circulation and two groups with an extracorporeal flow of 10-12 ml/kg/min, one of which was given prostacyclin (70-110 ng/kg/min). The extracorporeal circulation triggered a decrease in arterial saturation (from 99 to 91%) and carbon dioxide elimination (increase in arterial to end-tidal PCO2 by about 1 kpa) a metabolic acidosis (pH approximately 7.20), a platelet consumption (approximately 50%) and shortened survival time, side-effects reduced by prostacyclin. Further, there was a marked increase in haemoglobin concentration indicating hypovolemia via capillary fluid filtration. None of these side-effects were seen in the control group. Extracorporeal circulation as a trigger for pulmonary dysfunction and for impaired tissue nutrition with possible beneficial effects of prostacyclin is discussed, and also form a clinical point of view (i.e. extracorporeal lung assistance, ECLA), on the basis of the results. PMID- 1613193 TI - Pulse oximetry in severe anaemia. AB - Measurement of arterial oxygen saturation by pulse oximetry was performed in two patients with acute and chronic anaemia (haemoglobin concentrations: 2.9 mmol/l (4.7 g/dl) and 1.9 mmol/l (3.0 g/dl), respectively) using a Radiometer OXI and a Nellcor N-200 pulse oximeter. The two oximeters read alternating different values in the two patients. In conclusion, pulse oximeters are able to give a value for oxygen saturation even at extreme anaemia, and when a high value is given, it possibly reflects arterial oxygen saturation. The value of pulse oximetry in severe anaemia is discussed. PMID- 1613194 TI - Mediastinitis due to Nocardia asteroides after cardiac transplantation. AB - Nocardia infection classically occurs in immuno-compromized patients. Only a few cases of mediastinal infection due to this pathogen have been described in the literature. We report a patient who developed mediastinitis due to Nocardia asteroides after cardiac transplantation. The treatment was surgical debridement, dressing, sugaring and antibiotic therapy. The emergence of a severe acute renal failure possibly induced by drug interaction between Cyclosporin, cyclines and aminoglycosides, led us to modify the antimicrobial treatment. The intravenous use of Imipenem 2 g per day and Ciprofloxacin 400 mg per day for four weeks and then oral Ciprofloxacin 1.5 g per day for 1 year, was effective and allowed a good outcome, without any drug interaction with Cyclosporin, adverse effect, graft rejection episode or infection relapse. PMID- 1613195 TI - Theophylline toxicity causing rhabdomyolysis and acute compartment syndrome. AB - A case of acute compartment syndrome is described in a young man as a result of theophylline toxicity. Profound hypokalaemia and grand mal seizures are considered as potential causes of rhabdomyolysis and the subsequent development of compartment syndrome. PMID- 1613196 TI - Continuous measurement of hepatic vein oxygen saturation with a new catheter. PMID- 1613197 TI - Factitious acute hypercalcemia biological interference between calcium and lipids. PMID- 1613198 TI - Legionnaire's disease and rhabdomyolysis. PMID- 1613199 TI - IMPRV--synchronized APRV, or more? PMID- 1613200 TI - Not awake, not asleep, not dead? PMID- 1613201 TI - Continuous positive airway pressure (CPAP) vs. intermittent mandatory pressure release ventilation (IMPRV) in patients with acute respiratory failure. AB - Intermittent Mandatory Pressure Release Ventilation (IMPRV) is a positive pressure spontaneous breathing ventilatory mode in which airway pressure is released intermittently and synchronously with patient's spontaneous expiration in order to provide ventilatory assistance. Eight critically ill patients free of any factor known to alter chest wall mechanics (group 1) and 8 critically ill patients whose spontaneous respiratory activity was markedly altered by a flail chest, or by a C5 quadraplegia and/or by the administration of opioids (group 2) were studied prospectively. CPAP and IMPRV were administered to each patient in a random order during a 1 h period using a CESAR ventilator. Gas flow, tidal volume, tracheal pressure, esophageal pressure, end-expiratory lung volume and hemodynamic parameters were measured. In group 1 patients, the ventilatory assistance provided by IMPRV was associated with a significant decrease in spontaneous tidal volume whereas all other respiratory parameters remained unchanged. In group 2 patients, IMPRV increased minute ventilation from 8.0 +/- 2.61/min to 12.2 +/- 1.81/min (p less than 0.05), decreased PaCO2 from 46 +/- 7.3 mmHg to 38 +/- 6.8 mmHg (p less than 0.05) and reduced respiratory frequency from 21 +/- 10 bpm to 14 +/- 5.7 bpm (p less than 0.07). These results show that IMPRV provides significant ventilatory assistance to patients with mild acute respiratory failure either by decreasing patient's contribution to minute ventilation or by increasing alveolar ventilation in presence of respiratory depression of central or peripheral origin. PMID- 1613202 TI - Determination of cerebral perfusion by means of planar brain scintigraphy and 99mTc-HMPAO in brain death, persistent vegetative state and severe coma. AB - A total of 24 patients with clinical evidence of brain death (n = 17), severe coma (n = 2; GCS approximately 3) and apallic syndrome (n = 4) underwent a comparative investigation with 99mTc-HMPAO brain scintigraphy, EEG, auditory and somatosensory evoked potentials. Accompanied by EEG and evoked potentials, brain scintigraphy enabled confirmation of cerebral death in 15/17 patients. In one case clinical examination and evoked potentials suggest brain death, but cerebral perfusion and EEG were normal ("brain stem death"). One patient with evidence of cerebral death in clinical examination, brain scintigraphy and evoked potentials, showed questionable focal EEG activity; however, autopsy revealed intravital autolysis of the entire brain. All patients with apallic syndrome and deep coma showed a distinct cerebral perfusion, but gross EEG abnormalities; evoked potentials were delayed or absent. Planar scintigraphy with 99mTc-HMPAO appears to be superior to neurophysiological techniques discriminating patients with agonal cerebral dysfunction from those with brain death. PMID- 1613203 TI - Results of four technical investigations in fifty clinically brain dead patients. AB - Fifty consecutive patients (aged 19-77 years, median 56 years) with primary cerebral diseases and the clinical signs of absent cortical and brainstem function were subjected to electroencephalography (EEG), brainstem acoustic evoked potentials (BAEP), extracranial Doppler ultrasonography (ECD) and arterial digital subtraction angiography (DSA). In the majority of cases the results of the technical tests agreed with the clinical signs and were suggestive of brain death. However, in one patient EEG revealed clear bioelectrical activity. In 6 cases, doubts existed about whether the EEG was isoelectric; in 3 of the 6 cases biological activity might have been present. In 31 of 42 patients ECD showed a typical pattern of intracranial circulatory arrest, in 9 of 42 ECD revealed a pattern suggestive of the cessation of cerebral blood flow. In four patients BAEP recordings compatible with brain death were recorded 2-3 days before intracranial circulatory arrest. In 2 patients with isoelectric EEG and absent BAEP arterial DSA demonstrated residual perfusion. The findings are discussed in view of the conceptional differences concerning brain death. It is concluded that the strict application of the concept of death of the whole brain requires angiographic demonstration of absent intracerebral blood flow. PMID- 1613204 TI - Systemic vasomotor interaction between nicardipine and hypocapnic alkalosis in man. AB - The effects of hypocapnic alkalosis on the vasodilating action of nicardipine were studied in 6 patients after cerebral arterial aneurysm surgery. Each patient served as his/her own control during the 6 steps of the study. T0: baseline; T1: hypocapnic alkalosis alone (PaCO2: 3.5 kPa); T2: hypocapnic alkalosis and bolus injection of nicardipine (30 micrograms.kg-1 i.v.); T3: hypocapnic alkalosis and continuous 60 min infusion of nicardipine (0.5 microgram.kg-1.min-1), T4: determination of the infusion rate required to neutralize the effect of hypocapnic alkalosis; T5: same continuous dose of nicardipine as in T4 but reversal of hypocapnic alkalosis. Hypocapnic alkalosis alone caused a significant increase in the systemic vascular resistance index by 20% (T1). The bolus injection of nicardipine reversed this first effect (T2). The continuous infusion of nicardipine in T3 was insufficient to cancel the haemodynamic effect of hypocapnic alkalosis. During T4 the plasma levels required to neutralize completely the effect of hypocapnic alkalosis were twice those at T3. Normalization of the PaCO2 in step T5 induced a significant fall in the systemic vascular resistance index by 27.5% as compared with T0. In this study hypocapnic alkalosis modified the relationship between plasma levels of nicardipine and its expected vasoactive effects. This interaction was reversible. PMID- 1613205 TI - Adrenocortical function: an indicator of severity of disease and survival in chronic critically ill patients. AB - Plasma cortisol levels and modified Apache II (Apache IIm-stay) severity of disease scores were determined at weekly intervals in 159 patients who were treated for at least 7 days at the Critical Care Unit of our hospital. The mean (+/- SD) plasma cortisol level (0.60 +/- 0.28 mumol/l) was clearly elevated in these patients. The highest plasma cortisol levels were measured in patients treated with vasoactive drugs (0.76 +/- 0.39 mumol/l). Non-survivors (n = 36) had a significantly higher mean plasma cortisol level and Apache IIm-stay score than survivors (respectively 0.78 +/- 0.40 vs. 0.54 +/- 0.21 mumol/l; p less than 0.0003 and 12.6 +/- 4.8 vs. 7.3 +/- 4.1; p less than 0.0001). A significant correlation was found between the individual weekly plasma cortisol levels and the Apache IIm-stay scores (r = 0.41; p less than 0.0001), especially in the subgroup of patients, who never received glucocorticoids during their stay at the ICU (r = 0.51; p less than 0.0001). During the 14-month study period only two patients showed a clinical picture of adrenocortical insufficiency and a blunted response of cortisol to 0.25 mg synthetic ACTH(1-24). In conclusion, our data suggest that a high plasma cortisol level, like a high Apache IIm-stay score, indicates severity of disease and poor survival in critically ill patients. De novo adrenocortical insufficiency is rare and therefore routine screening of adrenocortical function is superfluous. PMID- 1613207 TI - Stimulation of three areas of the primary motor cortex interrupts micturition in dogs. AB - To clarify the area of the motor cortex (M1) in dogs, which corresponds to the cortical area participating in voluntary interruption of micturition in humans, the cortical portions related to the external urethral sphincter were first clarified by recording of somato-sensory evoked potentials, and then systematic cortical stimulation was performed in anesthetized and paralyzed dogs. The hypogastric, pelvic and pudendal nerves innervating the lower urinary tract and rectum were severed to eliminate the secondary reflexes. Five foci were recognized in the cortical potentials evoked after stimulation of the pudendal nerve. These foci existed in the sacral (Sacral-S) and hind leg (Leg-S) areas of the somato-sensory cortex (S1), and in the sacral (Sacral-M), hind leg (Leg-M) and trunk (Abd-M) areas of the M1. Stimulation of the three M1 foci, but not the two S1 foci, provoked centrifugal firings of the pudendal urethral branch. The firings disappeared after cutting of the ipsilateral bulbar pyramis. When the M1 foci were stimulated during the micturition reflex, the reflex discharge of a pelvic vesical branch was interrupted concomitantly with firings of the urethral branch. The interruption was still induced after the pyramidotomy. Pulse train stimulation of these M1 foci reset the cycles (about 2 Hz) in the alternative rhythmic firings of the urethral and vesical branches, which are known to be formed in the pontine micturition center [31,32]. These results suggest that the pyramidal cells in the three M1 foci inhibit the pontine micturition center and concomitantly contract the external urethral sphincter through the pyramidal tract. The possible roles of these M1 foci were discussed. PMID- 1613206 TI - Comparison of hydrophobic heat and moisture exchangers with heated humidifier during prolonged mechanical ventilation. AB - Inspired gases must be warmed and humidified during mechanical ventilation. In a prospective randomized study we compared the performance of a heated humidifier (HH) (Draegger Aquaport) and a heat and moisture exchanger (HME) (Pall Filter BB 2215). A total of 116 patients requiring mechanical ventilation (Servo 900 C Siemens) were enrolled into the study and were randomly assigned to 2 groups. Patients in group I were ventilated with a traditional breathing circuit with HH and patients in group II using a simplified circuit with HME. Pre-existing and hospital acquired atelectasis and pneumonia, occurrence of endotracheal tube (ET) occlusion and ventilatory parameters (respiratory rate, tidal volume) were studied. No statistical difference was found between groups for each parameter except the greater frequency of ET occlusions in the II group (0/61 vs 9/55) (p = 0.0008). Pall Filter (PF), a hydrophobic filter, humidifies the dry gases from the condensed water which is put down on the HME surfaces during cooling of saturated expired gases. This purely physical property is linked to the magnitude of the thermic gradient between the expired gases and the ambiant temperature. Performance impairment of PF in our study might be due to high ambiant temperature in the intensive care unit (usually around 28 degrees C) which reduces thermic gradient and water exchanges. We conclude that efficiency of PF may be weak in some conditions of ambiant temperature. PMID- 1613208 TI - Cardiac responses elicited by stimulation of loci within stellate ganglia of developing swine. AB - Stimulation with bipolar electrodes of specific loci in stellate ganglia elicited in anesthetized piglets, 1-4 weeks of age, alterations in cardiac function and aortic pressure. Responses were also elicited by chemical stimulation in specific loci of these ganglia. The probability of eliciting a cardiovascular response by stimulating loci in a stellate ganglion increased with increasing postnatal age. For instance, no responses were elicited when loci in the left stellate ganglia of 1-week-old piglets were stimulated. Significant heart rate responses were obtained only when loci in right stellate ganglia were stimulated. The number of ganglionic loci from which cardiovascular responses were obtained increased with increasing postnatal age. It is concluded that the capacity of stellate ganglion neurons to modulate the cardiovascular system matures during the first four weeks of life, heart rate being modulated primarily by neurons in the right stellate ganglion and inotropism by neurons in both stellate ganglia. PMID- 1613209 TI - Cyclophosphamide cystitis in rats: involvement of capsaicin-sensitive primary afferents. AB - The involvement of capsaicin-sensitive primary afferent neurons in cyclophosphamide (CYP)-induced cystitis has been investigated in rats. CYP (150 mg/kg) was administered 48 h before testing in both vehicle- and capsaicin- (50 mg/kg s.c., 4 days before) treated rats. Some experiments were also performed 96 h after bilateral removal of pelvic ganglia to produce bladder denervation. CYP administration produced a marked detrusor hyperreflexia which was abolished by capsaicin pretreatment, demonstrating that it is mediated through stimulation of capsaicin-sensitive afferent neurons. CYP administration was followed by a marked increase in bladder weight and plasma protein extravasation (measured by the Evans blue leakage technique). The latter effect was largely prevented by ganglionectomy but was aggravated by capsaicin pretreatment. The effect of capsaicin was suppressed by ganglionectomy. Isolated strips of detrusor muscle from CYP-treated animals developed less tension in response to various stimuli as compared to strips from vehicle-treated animals; however, when contractile responses were expressed as percentage of an internal standard (carbachol-induced contraction) no difference was evident between the two groups. The bladder content of calcitonin gene-related peptide, used as a marker of the bladder afferent fibres that are capsaicin-sensitive in adult rats, was slightly reduced as compared to controls, but the difference can be accounted for by the increased bladder weight. We conclude that CYP-induced cystitis is not accompanied by a toxic effect on bladder nerves and that the decrease in bladder capacity is entirely mediated through stimulation of capsaicin-sensitive afferent fibres, presumably linked to the formation of the irritant metabolite of CYP, acrolein.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613210 TI - Medullospinal vasomotor neurones mediate hypotension from stimulation of prefrontal cortex. AB - Electrical stimulation of the prefrontal cortex in anaesthetised, paralysed rats evokes transient hypotension. In this study we have endeavoured to determine whether this evoked response is mediated by the spinal cord-projecting vasomotor neurones of the rostroventrolateral medulla (RVL). The responses of RVL-spinal vasomotor neurones to electrical stimulation of the prefrontal cortex caused a period of inhibition of the neuronal activity in the majority of cases (11 out of 13 neurones tested, 85%) and a short period of excitation in the remaining 2 neurones (15%). The prefrontal cortex-evoked inhibition of RVL-spinal vasomotor neurones was eliminated by iontophoretic application of bicuculline, a GABAa receptor antagonist, to the RVL-spinal vasomotor neurones. Microinjection of 50 nl of bicuculline methiodide into the same area of the RVL where the neurones have been identified converted the prefrontal-evoked hypotension into a vasopressor response. These findings indicate that the hypotension evoked by stimulating the prefrontal cortex is mediated by GABAergic inhibition of the RVL spinal vasomotor neurones. PMID- 1613211 TI - Ganglionic and arterial release of neuropeptide Y by bullfrog sympathetic neurons. AB - Sympathetic C neurons in lumbar paravertebral ganglia of the bullfrog have previously been shown to be vasomotor in function and to express neuropeptide Y (NPY). In the present experiments, a sensitive radioimmunoassay was used to measure the NPY content of ganglia and the descending abdominal aorta and to measure the overflow of NPY evoked by depolarizing concentrations of K+. Paravertebral ganglia 9 and 10 contain 3.1 pg NPY/micrograms protein and the aorta contains 0.18 pg NPY/micrograms protein. During 20-min depolarizations in high K+ (58 mM) Ringer, the ganglia released approximately 5% of their NPY content and the aorta released approximately 2% of its NPY content. Pretreatment of the tissues with Ringer containing 0.18 mM Ca2+, 8 mM Mg2+, and 1 mM Co2+ blocked the NPY release elicited by high K+. These findings provide further evidence that NPY is a postganglionic co-transmitter in sympathetic C neurons of the bullfrog. PMID- 1613212 TI - Computer-generated bone models in the planning of osteotomy of multidirectional distal radius malunions. AB - Computer-assisted design and manufacturing technology has been used to create solid models of five unusually complex, multidirectional malunions of distal radius fractures. Preoperative planning was dramatically enhanced by the ability to perform the surgical procedure on these models, with a model of the uninjured limb used for comparison. All five patients had significant malunions, with malrotation in the horizontal plane in five and an impacted articular fragment in two. A satisfactory outcome was achieved in each case. PMID- 1613213 TI - Intraoperative distraction in the treatment of complex nonunions of the radius. AB - Two unique cases of complex nonunions of the radius are presented. Each was characterized by bone loss, disruption of the distal radioulnar joint, and loss of axial alignment. Indirect reduction and lengthening of the radius were accomplished intraoperatively with the use of a femoral distractor, and the nonunion was treated with autogenous iliac crest graft and a long AO/ASIF dynamic compression plate. A functional result occurred in each case. PMID- 1613214 TI - Force transmission through the distal ulna: effect of ulnar variance, lunate fossa angulation, and radial and palmar tilt of the distal radius. AB - The relationship between the amount of force transmitted through the distal ulna and seven radiologically apparent anatomic parameters (ulnar variance, radial tilt, palmar tilt, lunate fossa angulation, carpal height, carpal ulnar distance, and ulnar head inclination) was examined in 58 fresh cadaver forearms. A positive, although very weak, relationship was found between the amount of force and the ulnar variance (r = 0.44). This suggests that a clinically more positive ulnar variant wrist will not necessarily cause more force to be transmitted to the head of the ulna than a wrist with a more negative ulnar variance, primarily because the triangular fibro-cartilage complex is thicker in arms with a more negative ulnar variance. Changes in ulnar variance of a forearm due to ulnar lengthening or radial shortening do, however, dramatically alter the force transmission. No other relationships were found between the ulnar force and the other radiologic parameters. PMID- 1613215 TI - The effects of scaphoid intercarpal stabilizations on wrist mechanics: an experimental study. AB - A fresh cadaver study of the effects of a variety of scaphoid stabilizations on wrist motions is reported. Scaphoid-trapezium-trapezoid stabilizations with the scaphoid in its normal anatomic position and the same stabilizations with the scaphoid in malposition, either vertical or horizontal in relation to the radius, were compared. Scaphoid-capitate stabilizations with the scaphoid in its normal position were also studied. With the scaphoid vertical, a scaphoid-trapezium trapezoid stabilization resulted in greater loss of wrist flexion and ulnar deviation whereas, with the scaphoid horizontal, wrist extension and radial deviation were more severely affected than when the scaphoid was stabilized in its normal position. With the scaphoid in its anatomic position, both scaphoid trapezium-trapezoid and scaphoid-capitate stabilizations resulted in similar patterns of wrist motion. PMID- 1613216 TI - Strain-gauge evaluation of lunate unloading procedures. AB - A biomechanical study was undertaken to determine which procedure(s) most effectively relieve load from the lunate. Strain gauges were mounted on the lunates of 20 preserved cadaveric limbs. Three types of procedures were performed: scaphotrapeziotrapezoid arthrodesis, capitohamate arthrodesis, and ulnar lengthening. Load testing was performed both before and after the simulated fusions and ulnar lengthenings. Ulnar lengthening of 3 mm was the most effective method of lunate strain reduction. Capitohamate arthrodesis decreased compressive strain but increased shear strain. Scaphotrapeziotrapezoid fusion significantly increased both compressive and shear strain in the lunate. Of the three procedures that were tested, ulnar lengthening to create a neutral variance is the most reliable means of unloading the lunate. PMID- 1613217 TI - Distribution of pressures and forces on the wrist after simulated intercarpal fusion and Kienbock's disease. AB - Limited intercarpal fusion has been recommended for the treatment of Kienbock's disease. The effects of a simulated scapho-trapezio-trapezoid (STT) fusion and simulated Kienbock's disease on the biomechanics of the radio-ulno-carpal joint were investigated. The percent force, the centroid of the force, and the percent contact area in each fossa were determined. It was found that a STT fusion with the scaphoid in a neutral or extended position unloads the lunate fossa. STT fusion in flexion does not affect lunate load. It is concluded from this biomechanical experiment that STT fusion with the scaphoid in a neutral or extended position unloads the radiolunate joint regardless of the condition of the lunate. This load is shifted to the radioscaphoid articulation. PMID- 1613218 TI - X-ray evaluation of radial shortening for Kienbock's disease. AB - The effect of inclination of the distal radius to subsequent lunate collapse is controversial. Therefore we evaluated the postoperative x-ray course of 10 patients with stage II, III, or IV Kienbock's disease who were treated only with radial shortening and followed up for an average of 25 months. The three patients who became worse as determined by x-ray evaluation had lunate fossa inclinations of less than 12 degrees after surgery. The four patients who improved had lunate fossa inclinations greater than 12 degrees. Appropriate radial shortening with adjunct wedge osteotomy to increase lunate fossa inclination may prevent further lunate collapse. PMID- 1613219 TI - Spontaneous atraumatic, nonrheumatic rupture of the extensor pollicis longus tendon: a case report. PMID- 1613220 TI - Sports-induced spontaneous rupture of the extensor pollicis longus tendon. AB - Two cases of spontaneous extensor pollicis longus tendon rupture are presented. One occurred in a 17-year-old diver and the other in a 69-year-old physician tennis player. Neither patient experienced pain, and only the diver had premonitory wrist discomfort. The diver was treated by an extensor indicis proprius transfer. The physician denied any disability and elected to have no treatment. PMID- 1613221 TI - Osteoid osteoma of the elbow: a report of six cases. AB - We report six cases of osteoid osteoma of the elbow. Elbow pain was the presenting complaint in all of these young adult patients. A variety of diagnoses were entertained, and four patients underwent surgical procedures that were not helpful. Although an abnormality was identified on plain x-ray films, tomograms and a bone scan were helpful in isolating the lesion. A CT scan proved valuable in two cases. Complete en bloc excision relieved pain and improved function in each case. PMID- 1613222 TI - Subperiosteal osteoid osteoma of the hamate: a case report. AB - Osteoid osteoma is uncommon in the hand. The lesion can arise from either cortical or cancellous bone or subperiosteally. The latter localization is extremely rare in the hand, with only 4 reported cases in the English-language literature. Furthermore, characteristic radiographic findings of a central lucency surrounded by reactive sclerosis often emerge only late in the process, or not at all. Consequently, the diagnosis of osteoid osteoma of the hand can be delayed. We report a case of a subperiosteal osteoid osteoma of the hamate in which the diagnosis was delayed 2 years. PMID- 1613223 TI - Chondroblastoma of the lunate: a case report. PMID- 1613224 TI - Subungual exostosis of the fingers. AB - Subungual exostosis in the digit is an uncommon benign tumor. Only 21 (10%) of 203 cases reported in the literature occurred in the hand. We present a recent case, detailing diagnosis, pathologic findings, and management. PMID- 1613225 TI - Digital pacinian corpuscle neuroma eroding bone: a case report. AB - A case of digital pacinian corpuscle neuroma leading to erosive changes in the adjacent proximal phalanx is reported. Characteristics and previous reports of this relatively uncommon hand tumor are discussed. PMID- 1613226 TI - Leiomyosarcoma of the skin and subcutaneous tissue of the hand and wrist. AB - Leiomyosarcoma of the skin and subcutaneous tissues is a rare tumor of smooth muscle origin. A case report of leiomyosarcoma of the hand is presented. The lesion was treated with wide local excision and has shown no recurrence in 2 years of follow-up. PMID- 1613227 TI - Foreign body arterial embolus to the hand. PMID- 1613228 TI - Anterior wrist ganglia from the scaphotrapezial joint. AB - In this series of 104 anterior wrist ganglia evaluated, 35 were found to arise from the scaphotrapezial joint, 1 from the metacarpotrapezial joint, and 68 from the radioscaphoid joint. After dissection of the cyst and identification of the joint of origin, the ganglion was removed and the joint was incised. Of the patients with scaphotrapezial ganglia, 29 were available for follow-up evaluation with a mean follow-up time of 67 months. Relief of symptoms was noted in 93%, wrist motion was maintained in all patients, and there were two recurrences. PMID- 1613229 TI - Bilateral scaphoid ganglion cysts in an adolescent. AB - We describe an adolescent girl with symptoms secondary to bilateral, symmetrical ganglion cysts of the scaphoid bones. From the roentgenographic and operative findings, it was believed that the cysts were the penetrating type. The patient is among the youngest reported with carpal bone ganglion cysts and the first with bilateral scaphoid cysts completely described in the English-language medical literature. PMID- 1613230 TI - Dislocation of the carpal scaphoid: an 8-year follow-up. AB - Isolated dislocation of the carpal scaphoid is a rare injury, with 10 cases reported in the English-language literature. We report an 8-year follow-up of a dislocated scaphoid treated with open reduction and Kirschner wire fixation. Good to excellent range of motion was the result. PMID- 1613231 TI - Proximal and distal oblique radiography of the wrist: value in occult injuries. AB - Fractures of the scaphoid and capitate bones are frequently nondisplaced at the initial examination. In addition, obliquity of the fracture line may result in the fracture not being profiled on routine views. Angling the radiographic tube 30 degrees off the vertical toward the elbow results in elongation of the scaphoid and capitate bones and improves visualization of the scaphoid over routine posteroanterior radiographs. Reversing the angle of the tube to 30 degrees from the vertical toward the fingertips further elongates the capitate. This is useful for delineating occult fractures of the capitate. PMID- 1613233 TI - Nonoperative treatment of acute hamate hook fractures. AB - Six patients with acute and two patients with subacute nondisplaced fractures of the hamate hook were treated with immobilization. The patients with acute fractures were treated within 7 days of the injury, and those with subacute fractures were treated after 7 days. Seven of the eight patients showed documented healing of their fractures. At follow-up (average 8 months) all seven were free of symptoms. One patient with a subacute fracture did not comply with treatment and had a painful nonunion. Our results show that hamate hook fractures that are diagnosed early may heal with nonoperative management. Fractures that fail to heal with immobilization or those with chronic nonunion should be treated with excision of the hook fragment. PMID- 1613232 TI - The reverse oblique x-ray film: metacarpal fractures revealed. PMID- 1613234 TI - Acute open reduction and rigid internal fixation of proximal interphalangeal joint fracture dislocation. AB - We report the application and results of a technique of open reduction and rigid internal fixation of dorsal fracture/dislocation of the proximal interphalangeal joint with an interfragmentary screw in two cases. Articular congruity was restored, and the proximal interphalangeal joint was stabilized. This technique permitted immediate range-of-motion exercises. Excellent results were obtained in both cases. Previous descriptions have not detailed the indications, the surgical approach, or the results of this technique. PMID- 1613235 TI - Tension band arthrodesis of finger joints: a retrospective review of 76 consecutive cases. AB - Arthrodesis of finger joints is a reliable method of treating finger joint instability and arthritis. Tension band arthrodesis is an effective method of stable fixation that uses readily available and inexpensive materials. Because fixation is rigid, patients are allowed to move adjacent joints, usually within 1 week after surgery. The results of 76 tension band arthrodesis procedures performed since 1982 in 63 patients were reviewed. Follow-up ranged from 6 to 38 months. The average time to radiographic fusion was 12 weeks (range, 4 to 64 weeks). One joint failed to fuse and developed a stable, asymptomatic nonunion; thus the fusion rate was 99%. Technical problems that occur with the method include nonparallel pin placement and penetration of pin tips, leading to painful impingement of the soft tissues. A pin-placement guide has been developed to minimize these problems. PMID- 1613236 TI - One-stage key pinch and release with thumb carpal-metacarpal fusion in tetraplegia. AB - One-stage key pinch and release with carpal-metacarpal fusion, extensor pollicis longus tenodesis, and motor transfer to flexor pollicis longus were analyzed for functional results in tetraplegic patients. Eighteen patients (21 hands)--all with International Classification OCu:4 hand function or worse--were studied. Average follow-up was 42 months. All patients experienced significant increase in functional ability and thought the surgery was highly beneficial. Average pinch strength was 3.3 kg, whereas it had been nonmeasurable preoperatively. Both activities of daily living and pinch strength correlated with tetraplegic functional level. The patients with higher preoperative functional level had better postoperative activities of daily living scores and pinch strength. Sixteen hands had solid fusions, and patients with fibrous nonunions showed no decrease in pinch strength, pain, or functional limitations when compared with the patients who had solid fusions. Six hands showed degenerative changes at one or more adjacent joints, but this was not related to results. PMID- 1613238 TI - Digital pulley reconstruction with expanded polytetrafluoroethylene (PTFE) membrane at the time of tenorrhaphy in an experimental animal model. AB - Digital pulley reconstruction with a synthetic material, PTFE membrane, was compared with suture repair of the native A3 pulley at the time of tenorrhaphy in the chicken model. The surgically treated foot was immobilized in flexion for either 28 or 35 days and then allowed full ambulation for periods of up to 42 days postoperatively. At sacrifice digits underwent range-of-motion testing, and the pulley and tenorrhaphy sites were explored. No disruptions were noted in the reconstructed PTFE pulleys. The number of tenorrhaphy disruptions was similar between the PTFE pulley group (11%) and the suture repair of the native pulley group (14%). No decrease in range of motion was demonstrated in the PTFE pulley digits, and no deleterious effect of increasing immobilization time (35 days versus 28 days) was noted. The results indicate that this synthetic pulley did not interfere with normal tendon healing processes. PTFE membrane may prove to be a promising reconstructive alternative when the native pulley is irreparably damaged. PMID- 1613237 TI - Gap formation during controlled motion after flexor tendon repair in zone II: a prospective clinical study. AB - Intratendinous metal markers were used to study the formation of gaps in flexor digitorum profundus tendon repairs during and after early controlled motion with dynamic flexion traction and to evaluate their significance for results in 34 digits with repairs in zone II. The mean (+/- SD) final repair elongation was 3.2 (+/- 3.6) mm. Linear regression analysis showed a general trend toward an inverse relationship between elongation and clinical results in terms of active interphalangeal joint range of motion, but the correlation was weak, and in the individual case gap formation was a poor predictor of clinical result. Gaps of up to 10 mm were quite compatible with good function. The results indicate that controlled motion is effective in restricting the formation of adhesions associated with gap formation during postoperative immobilization. PMID- 1613239 TI - Genetic expression for type I procollagen in the early stages of flexor tendon healing. AB - To determine the precise mechanism by which contact tendon healing occurs at the cellular level, the production of pro alpha (I) collagen messenger RNA (mRNA) produced by fibroblasts of healing intrasynovial flexor tendons was determined by an in situ hybridization technique. The repair site and the proximal and distal tendon stumps of repaired tendons treated with early controlled passive mobilization were fixed and buffered in formalin, 3, 7, 10, and 17 days after repair. A complimentary DNA (cDNA) probe corresponding to alpha (I) procollagen mRNA was labeled with [32P]d-CTP. After hybridization, autoradiography, and staining of the sections, the level of procollagen mRNA was assessed by microscopic examination. Rising levels of procollagen mRNA, indicating progressively increasing levels of synthetic collagen activity, were detected in the healing tendons through 10 days. A moderate decrease in procollagen mRNA was seen at 17 days. Genetic expression for procollagen mRNA was localized specifically to the epitenon cells on the tendon surface overlying the repair site and to cells in the gap between the tendon stumps. No detectable expression was noted in endotenon fibroblasts. The finding of high levels of expression for procollagen type I mRNA in the surface layer of healing tendons demonstrates that cells intrinsic to tendon epitenon contribute the greatest quantity of native tendon collagen to the repair site during these important early intervals after tendon suture. PMID- 1613240 TI - Comparative flexor tendon excursion after passive mobilization: an in vitro study. AB - Two experimental studies were conducted to investigate flexor tendon excursions. In the first study, tendon excursions due to passive joint motion in various loading condition were evaluated. In the second study, the efficacy of a new technique that used synergistic wrist motion (S-splint) was compared with the traditional dorsal splinting methods: the Kleinert splint (K-splint) and the Brooke Army Hospital/Walter Reed modified Kleinert splint with a palmar bar (P splint). The results of these studies question the anticipated tendon excursion associated with postoperative splinting. They demonstrated that the measured tendon excursion under a condition of low tendon tension was almost half that of theoretically predicted values. In zone II, the magnitude of excursion introduced by the three mobilization methods were in descending order: S-splint, P-splint, K splint (p less than 0.05). Differential tendon excursion between the flexor digitorum profundus and the flexor digitorum superficialis had a mean value of 3 mm and was not significantly different among the three methods. Passive proximal interphalangeal joint motion was the most effective means of providing increased amplitude of tendon gliding in zone II. Passive distal interphalangeal joint motion did not increase excursion in zone II as much as had been predicted. PMID- 1613241 TI - Arm anomalies and bone marrow failure may go hand in hand. AB - Children with congenital anomalies involving the hand, the forearm, or both are often seen by hand surgeons. An unknown proportion have inherited bone marrow failure syndromes, such as Fanconi's anemia, Diamond-Blackfan anemia, thrombocytopenia-absent radii, and others. In many cases the hematologic cytopenias are not yet apparent at the time of surgery. This review discusses these syndromes, summarizing the types of malformation, the types of hematologic complication, and the ages at which they occur. There are often clues in otherwise normal hematologic data, such as macrocytic red cells or slow decreases in blood counts that are still at a level at which surgery can be performed. Early and often presymptomatic diagnosis is of value for the planning of staged surgery before cytopenias preclude intervention, the performance of surgery after hematologic improvements, and genetic counseling for young families in which syndromes with a known inheritance pattern might be detected in utero. Hand surgeons may be the first to make these important diagnoses. PMID- 1613242 TI - Chronic Lyme disease arthritis: review of the literature and report of a case of wrist arthritis. AB - A case of Lyme arthritis with advanced degenerative changes localized to the midcarpal joint was treated with a limited wrist arthrodesis with relief of pain and improved function. Chronic Lyme arthritis occurs as the third stage of Lyme disease. Serologic testing and a history of a characteristic rash may be helpful in the diagnosis. Radiographic and histopathologic findings are nonspecific, with both degenerative and inflammatory characteristics. Intravenous antibiotics provide an effective treatment of chronic Lyme arthritis. PMID- 1613244 TI - Deepithelialized pedicle flap placed subcutaneously for fingertip reconstruction. AB - Fingertip injuries are common, but treatment may produce misshapened, clubbed, and painful results. The technique described here has given consistently excellent results in fingertip coverage in 74 patients with 96 fingertip injuries from 1976 through 1986. In this technique deepithelialized pedicle flaps provide soft tissue coverage before skin closure. PMID- 1613243 TI - Drug and alcohol use in emergency hand patients. AB - Two hundred eleven adult emergency hand patients were prospectively tested over a 1-year period for drug and alcohol use. On admission, blood and urine samples were sent for quantitative alcohol and qualitative toxicology screens, respectively. In 44% of all patients tests were positive for one or more drugs or alcohol. Tests were positive in 43% of those with traumatic injuries. Of patients injured on the job, 33% had positive tests. Tests were positive in 63% of those patients with hand infections. One third of the patients with positive toxicology screens were multiple drug users. These findings have obvious implications for the patient, the physician, and society as a whole. PMID- 1613245 TI - A knotted tendon for a spacer in interpositional arthroplasty. PMID- 1613246 TI - Flexor sheath continuity. PMID- 1613247 TI - Statistical properties of immunoanalytic system. PMID- 1613248 TI - Artifacts and limitations of enzyme immunoassay. PMID- 1613249 TI - Diagnostics for the tropical countries. PMID- 1613250 TI - Tumour markers in oncology: past, present and future. AB - Historically, tumour markers are substances selectively released by tumour cells in the blood stream so that they can be detected in the serum or other body fluids for clinical monitoring of various malignancies. The term is now extended to cell or tissue characteristics, such as cytogenetic markers, oncogenes or abnormally expressed proteins with various biological functions (enzymes, receptors, etc.), which help characterize the tumour type and constitute specific biological targets for new drugs. Serum markers can be classified in three main categories: (i) oncofetal antigens which are normally expressed only during fetal life, (ii) carbohydrate antigens as part of glycolipids or glycolipoproteins (mucins) and (iii) miscellaneous, including tissue specific enzymes, cytoskeletal proteins, etc. Most carbohydrate antigens which are useful in serum diagnosis of human cancers show tumour type-specific aberrant glycosylation, with O instead of N linkage to protein moieties. Despite a huge progression in analytical performances with immunoassays, and because of still insufficient biological sensitivity and specificity, serum assays of tumour markers are not effective in mass screening, their usefulness being restricted to the follow-up of diagnosed patients. Selective expression of specific antigens allows in vivo detection of occult tumour masses (immunoscintigraphy) and immunotargetting of drugs as therapy. Cell and tissue markers comprise markers of transformation (molecular genetics, oncogenes and anti-oncogenes, etc.), differentiation (hormone receptors, etc.), proliferation (growth factors, Ki67, etc.) and metastatic potential (proteases, etc.). Although masking the functional aspects of many of these markers, as for hormone or growth factor receptors, immunoanalytical methods, specially immunohistochemistry, are rapidly expanding in clinical oncology as tools for diagnosis, prognosis and, promisingly, treatment adjustment. PMID- 1613251 TI - The use of catalyzed reporter deposition as a means of signal amplification in a variety of formats. PMID- 1613252 TI - Detection of cell-surface molecules, secreted products of single cells and cellular proliferation by enzyme immunoassay. PMID- 1613253 TI - Diagnosis of autoimmune diseases. PMID- 1613254 TI - Contributions of peroxidase immunocytochemistry in the ultrastructural detection of membrane bound antigens. PMID- 1613255 TI - Reverse ELISPOT assay for clonal analysis of cytokine production. II. Enumeration of interleukin-1-secreting cells by amplified (avidin-biotin anti-peroxidase) assay. AB - Detection of cytokine-producing cells can be accomplished by reverse modifications of the ELISPOT assay using cytokine-specific unconjugated and enzyme-labelled antibodies as solid phase capture system and detecting reagents, respectively. However, in certain situations where the secreted cytokine is produced in minute amounts such as in the case of interleukin-1 (IL-1), the sensitivity of the indicator immunoenzyme system employed may be insufficient to permit detection of the corresponding secreting cells. We have developed a novel immunoenzyme amplification procedure that involves the use of a biotinylated secondary anti-enzyme antibody reagent to enhance the signal provided by the primary enzyme-labelled antibody conjugate. Following addition of enzyme conjugated avidin, ELISPOT assay wells are developed with a suitable chromogen substrate yielding spots located at the former position of cells secreting the analyte under study. As a model system, the detection of IL-1 beta-secreting cells by human peripheral blood monocytes is described. PMID- 1613256 TI - Amplification systems in immunoenzymatic techniques. PMID- 1613257 TI - Immunoenzymatic techniques applied to the specific detection of nucleic acids. A review. AB - Numerous enzymatic and chemical methods are now available for the preparation of non-radioactive nucleic acid probes. Labels, such as enzymes, fluorophores, lumiphores can be attached to the nucleic acid probe either by covalent bonds (direct labelling) or by biospecific recognition after hybridization (indirect labelling). The principle of the latter method is based on the use of a hapten labelled nucleic acid probe which is generally detected by an immunoenzymatic assay. Indirect labelling has several advantages: this procedure uses multienzyme complexes to increase the number of enzyme molecules associated with hybridization and hence provides an increase in detectability; moreover, haptens (biotin, dinitrophenol, acetylaminofluorene analogues, digoxigenin, brominated or sulphonylated pyrimidines) used to label nucleic acid probes are not sensitive to elevated temperatures (42-80 degrees C), extended incubation times (several hours), detergents and organic solvents currently required in hybridization techniques. The application of the immunoenzymatic and related techniques to nucleic acid probing is reviewed, focussing on the strategies of non-radioactive hybridization, hapten-labelling of nucleic acids and methods for the immunodetection of the hybrids. PMID- 1613258 TI - Enzyme immunoassay techniques. An overview. AB - In spite of the great variety of enzyme immunoassays (EIA) they can be classified into two groups 'analyte-observed' and 'reagent-observed' assays, depending on their reaction principle. The latter are favored by use of monoclonal antibodies and are characterized by a greater sensitivity, a larger measuring range, a lower susceptibility to disturbing influences. They can be used only for detection of macromolecules. For heterogeneous EIAs to be used on laboratory scale, simple adsorption of antigens and antibodies is still recommendable though affinity constants decrease by at least one order of magnitude and antibody density at the solid phase and analyte binding capacity are not parallel due to increasing steric hindrance. For this reason, the antibody with the higher affinity constant should therefore always be used as solid-phase antibody. Microparticles used as solid phase for heterogeneous assays, due to their very high binding capacity for the analyte and extremely short diffusion distances, guarantee 'one step' assays of only a few minutes. Of the limited number of enzymes suitable as markers in immunoassays, horseradish peroxidase is the enzyme of choice followed by alkaline phosphatase. Although enzyme and enzyme-labelled reagents are detectable by fluorogenic product measuring with a sensitivity, which is 10-1000 times higher than using chromogenic substrates, the sensitivity of the assays can be increased only by factor 2-10. Labelling enzymes cannot only be covalently bound to the antibody, but also via anti-enzyme antibodies. Pros and cons of the different methods of coupling the enzyme/anti-enzyme complex to analyte-containing immune complexes are discussed. Different EIA variants to detect specific antibodies are reviewed. Among them only capture EIAs permit precise isotype analysis of antibodies of a distinct idiotype. Homogeneous EIAs are widely spread for hapten determination but even variants based on proximal linkage are no alternatives to heterogeneous EIAs for determination of macromolecules. Different parameters are defined which permit to assess the quality of an immunoassay and which should be used in routine assays as internal controls in the laboratory. PMID- 1613259 TI - Titration of antibodies. PMID- 1613260 TI - The physical and functional behavior of capture antibodies adsorbed on polystyrene. AB - Six monoclonal and two polyclonal antibodies to fluorescein (FLU) were affinity purified and immobilized on Immulon 2 polystyrene as capture antibodies (CAbs): (a) by passive adsorption at pH 9.6, (b) via a streptavidin bridge to a biotinylated carrier molecule, and (c) via an antiglobulin which had been previously adsorbed passively to the polystyrene. Data show that less than 3.0% of the binding sites of monoclonal CAbs and approximately 5-10% of those of polyclonal CAbs were capable of capturing antigen (FLU4.2-BSA) after passive adsorption. Immobilization of CAbs via an antiglobulin or a streptavidin bridge, resulted in the preservation of antibody binding sites to greater than 70% for some monoclonals although immobilization via the streptavidin bridge resulted in the highest number of functional sites/well. The data presented are consistent with studies on other adsorbed proteins which demonstrate that passive adsorption on polystyrene results in the loss of protein function. Furthermore, these data show that generally less than half of the binding sites of antibodies available in solution are available after solid-phase immobilization even when non adsorptive methods are employed. Some polyclonal anti-FLU also have lower average avidity following passive adsorption compared with CAbs immobilization via a streptavidin bridge. Immunochemical studies revealed that adsorbed polyclonal CAbs performed like monoclonals when tested with multivalent antigens (FLU10-IgA) but in an expected heterogeneous manner in Scatchard plots when tested using univalent FLU-insulin. This observation implied cross-linking of immobilized CAbs by the multivalent antigen. Because only 5-10% of adsorbed polyclonal CAbs are active, the survivors must be non-randomly distributed in clusters to explain the cross-linking. This was confirmed by scanning electron microscopy which gave rise to the hypothesis that antibodies which retain activity after adsorption, are those present in clusters, i.e., the functional adsorbed CAb is an antibody cluster. Data presented in this report on the behavior of adsorbed CAbs, and reviewed from the work of others for various adsorbed proteins, indicate that the method of passive adsorption at pH 9.6, which is widely used in popular microtiter ELISAs, and which has in many ways revolutionized immunoassay, is a method of protein denaturation. Assayists that utilize passive adsorption of proteins on hydrophobic supports as part of their research need to be cognizant of this phenomenon, while inventors of immunoassay should develop alternative methods of immobilization which do not destroy 90% of the functional activity of solid-phase reactant. PMID- 1613261 TI - Homogeneous enzyme immunoassay. PMID- 1613262 TI - CEDIA in vitro diagnostics with a novel homogeneous immunoassay technique. Current status and future prospects. AB - CEDIA assays represent a state of the art technique utilizing two genetically engineered, enzymatically inactive fragments of beta-galactosidase as the basis for a homogeneous enzyme immunoassay. The smaller, amino-terminal polypeptide, designated the enzyme donor (ED), can recombine spontaneously with the large residual fragment, called the enzyme acceptor (EA), to form active beta galactosidase, in a process called complementation. ED have been designed in such a way that a ligand, such as a hormone or drug, can be chemically attached to a specific amino acid residue without affecting the enzyme complementation. However, the binding of a ligand-specific antibody to the ED-ligand conjugate will inhibit complementation. If a sample containing ligand is added to the reaction mixture, the ligand will compete with the ED-ligand conjugate for the limited number of antibody binding sites. Thus, the ligand concentration in the sample will modulate enzymatic activity by influencing the amount of free ED ligand conjugate available for complementation. The basic technology of CEDIA assays has a number of inherent advantages, the most important of these being a linear calibration curve with high precision over the whole assay range, lack of endogeneous enzyme activity and minimal serum interference, chemically defined conjugates and flexibility in assay design. These provide significant advantages in comparison to other homogeneous immunoassay techniques. As a result, CEDIA assays have been successfully developed for high concentration drugs such as theophylline, phenobarbital and phenytoin as well as for very low concentration analytes such as digoxin, B12 and folate. In a modified assay format, even the determination of binding proteins has been accomplished, an example being thyroxine binding proteins in the CEDIA T-uptake assay. More recently, the methodology has been extended to the measurement of high molecular weight analytes like ferritin. PMID- 1613263 TI - Molecular structure of the IL-3, GM-CSF and IL-5 receptors. AB - Reconstitution of high-affinity receptors using molecularly cloned receptor subunits has revealed that the high-affinity receptors for interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-5 are composed of two distinct subunits alpha and beta. Both subunits are members of the cytokine receptor superfamily that have the common structural motif in their extracellular domains. The alpha subunits are cytokine-specific, and each alpha subunit binds its specific ligand with low affinity. The human has a common beta subunit that does not bind any cytokine by itself but forms high-affinity receptors for GM-CSF, IL-3 and IL-5 with the respective alpha subunit. Therefore, cross-competition of binding between these cytokines occurs by competition for the common beta subunit between different alpha subunits in the human. In contrast, the mouse has two distinct beta subunits; one is specific for the IL-3 receptor, and the other is equivalent to the human common beta subunit. The beta subunits are not only required for high-affinity binding to ligands, but they are also essential for signal transduction. The high-affinity receptors induce protein tyrosine phosphorylation and activate the ras protein. However, neither alpha nor beta subunit has an intrinsic protein kinase, indicating that additional components are necessary for signal transduction. PMID- 1613264 TI - Novel factors from stromal cells: bone marrow and thymus microenvironments. AB - The microenvironments contained within mammalian bone marrow and thymus play major roles in the life-long process of myeloid and lymphoid cell development and renewal. The cells that give architecture to these microenvironments are collectively referred to as stromal cells, and these cells grow as adherent cell types in cell culture. Stromal cells are predominantly a mixture of fibroblasts, cells of macrophage/dendritic lineages, epithelial and endothelial cells. There are at least three mechanisms that govern the interaction of stromal cells with hematopoietic and lymphoid cells: soluble factors, or cytokines, membrane anchored growth factors and cell surface recognition molecules, such as integrins and selections. Little is known of the mechanisms that preserve the integrity of local microenvironments and how subpopulations of cells are transiently retained in microenvironments during various maturational states. Different lymphoid cells develop in bone marrow and thymus despite the similarities in stromal cells of these tissues. It remains a major quest to determine how the components of microenvironments of these organs regulate lineage-specific differentiation. The focus here is on stromal cells, the early development of myeloid cells and B lymphocytes in bone marrow and T lymphocytes in the thymus. PMID- 1613265 TI - Long-term survival of human myeloid progenitor cells induced by a mouse bone marrow stromal cell line. AB - Mouse endothelial-adipocyte cell line (14F1.1), which induces proliferation of mouse stem cells in culture, is also capable of supporting long-term survival in culture of human myeloid progenitor cells; colony forming unit granulocyte/macrophage (CFU-GM) was recovered from cultures incubated with the 14F1.1 cell line after over a month of incubation. The CFU-GM population increased beyond the input number, whereas, in control cultures initiated without stromal cells, the number of progenitors gradually declined. Addition of a relatively low concentration of human colony-stimulating factors (CSFs) into the cultures promoted the formation of "cobblestone areas," where mouse stroma and human hemopoietic cells closely interacted. 14F1.1 supernatant alone did not support the survival of human CFU-GM but synergized with the function of human granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate adherent macrophage proliferation. PMID- 1613267 TI - Effects of granulocyte-macrophage colony-stimulating factor and interleukin 6 on the growth of leukemic blasts in suspension culture. AB - We examined the stimulatory effects of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 6 (IL)-6 on the in vitro proliferation of leukemic blast cells from patients with acute leukemia. Bone marrow or peripheral blood leukemic blast cells were obtained from 21 patients, including 14 cases of acute myeloblastic leukemia (AML), four cases of acute lymphoblastic leukemia (ALL), two cases of acute undifferentiated leukemia, and one case of acute mixed-lineage leukemia. The proliferation of leukemic blast cells was evaluated by measuring the incorporation of 3H-thymidine into cells incubated with various concentrations of cytokines for 3 days. GM-CSF stimulated the DNA synthesis (with greater than 2.0 stimulation index) of blast cells in 9 of 14 (64%) AML cases, two cases of acute undifferentiated leukemia and one case of acute mixed-lineage leukemia. Only two cases of AML blasts responded to IL-6 to grow in the short-term suspension cultures. GM-CSF and IL-6 did not display a synergistic effect on the growth of leukemic cells. Moreover, GM-CSF and IL-6 did not stimulate the proliferation of ALL blast cells. Binding study also revealed the specific binding of GM-CSF on the blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia. Our results indicated that leukemic blast cells of acute undifferentiated leukemia and acute mixed-lineage leukemia possessed functional GM-CSF receptors. PMID- 1613266 TI - Enhancement of cell production in long-term bone marrow culture. AB - In an effort to increase the long-term production of hematopoietic cells in vitro, Origen hybridoma cloning factor (HCF) was added at the initiation of Dexter type cultures, in which whole bone marrow (BM) was seeded into tissue culture flasks and formed an adherent stromal layer that supported the proliferation and differentiation of primitive cells. After about six weeks, all the cultures were fully established, and continuous production of nonadherent cells was maintained for at least 27 weeks. In the groups with 20% HCF, there was a significant (three- to fourfold) increase in the steady-state cell production of 106 +/- 17 x 10(4) cells/ml compared to 26 +/- 10 x 10(4) in controls. In some cases the ability of HCF to increase productivity was limited by the nutrients and metabolic products in the culture medium. Cell number varied inversely with glucose and pH. HCF increased the concentration and absolute number of myeloid progenitors (granulocyte-macrophage colony forming units and spleen colony forming units) in the nonadherent layer and shifted the differentiation of granulocyte-macrophage colony forming units toward the production of cells of the monocyte/macrophage lineage. Spleen colonies produced from 10(5) cells from cultures with HCF were more numerous (8 +/- 2 versus 4 +/- 2) and larger than those from control cultures (2.6 versus 0.2 mg/colony), but they contained the usual cell lineages (erythrocytic, granulocytic and megakaryocytic). PMID- 1613268 TI - Hematopoietic stem cells and myeloid precursor cells in nonobese diabetic (NOD) mice. AB - Expression of diabetes susceptibility genes at the hemopoietic stem cell level is sufficient for the development of the disease in nonobese diabetic (NOD) mice. This work investigated whether the defects that reside within the stem cells have consequences on the homeostasis of the stem and progenitor cell compartments. The fraction of cyclically active stem cells, or spleen colony-forming units (CFU-s), is enlarged, and their differentiation toward megakaryocytopoiesis seems to be enhanced in NOD mice at 3 and 10 weeks of age as compared to C57BL/6 mice. Whereas colony-forming unit assay (CFU-A) numbers are normal in the bone marrow, they are significantly increased in the spleen of NOD mice. A strain-dependent difference in granulocyte-macrophage colony-forming cell (GM-CFC) numbers was observed; they were higher in NOD mice than in B6 mice of three and ten weeks of age. These results suggest that autoimmune type 1 diabetes mellitus of the NOD mouse is accompanied by disorders of myelopoiesis and megakaryopoiesis. This observation is in keeping with the role of macrophages in the development of diabetes and with the hyperactivity of diabetic platelets. PMID- 1613269 TI - Combination chemotherapy tested in a short-term thymidine incorporation assay in primary cultures of ovarian adenocarcinomas. AB - Fifty-six tumor specimens from patients with ovarian adenocarcinoma were tested for sensitivity to single and combination drug regimens in a short-term antimetabolic assay measuring inhibition of thymidine incorporation. Response in primary cultures to drug combinations was compared with response to each component drug: cisplatinum, chlorambucil, adriamycin, etoposide and activated cyclophosphamide. Using cut-off criteria previously shown to correlate with "sensitive" and "resistant" tumors for single drugs, 11% of tumors showed increased sensitivity to a combination compared with the single drugs, but 10% showed decreased sensitivity to a combination. The majority of tumors remained in the same "sensitive" or "resistant" categories obtained with the single drugs. Analysis by isobolograms demonstrated synergy, addition or antagonism with the same combination on different tumors. No significant difference between combinations and the best single drug used alone was found in 70% of assays. Overall thymidine incorporation inhibition by the combination and by the best single drug was highly correlated. It is suggested that the best single drug predicts the effectiveness of its combination regimens. PMID- 1613270 TI - Differential lysis of tumor target cells displayed by lymphokine activated killer (LAK) cell clones. AB - Lymphokine-activated killer (LAK) cells exhibit major histocompatibility complex (MHC) unrestricted cytolysis against a wide variety of fresh and cultured tumor cells. Because previous work from our laboratory suggested that trypsin treatment of unseparated populations of LAK cells had a differential effect on lysis of different tumors, in this report we analyzed the lytic specificity of LAK cell clones against a panel of three different targets: MCA, B16 and YAC-1. We found that 21 out of the 24 analyzed murine spleen and bone marrow clones killed a combination of two, but not all three, of these tumor cells. Determinations of the phenotype of 10 LAK cell clones showed six with rearrangements for the T cell receptor (TCR) beta chain gene, suggesting a T cell origin, and four with germ line configurations for the TCR beta and delta chain genes, a result consistent with a non-T cell lineage. This cloning procedure provided an experimental tool to develop new procedures of adaptive immunotherapy. PMID- 1613271 TI - [Classification of congenitally bicuspid aortic valve and its angiographic and surgical significance]. AB - From January, 1978 to December, 1990, 85 patients with congenital bicuspid aortic valve underwent aortic valve replacements (AVR) with St. Jude Medical valve prosthesis. We classified congenital bicuspid aortic valve into four types. Type I (44.7%): Two cusps are situated right and left, a coronary artery arises from each related sinus of valsalva. Type II (22.4%): Type I + raphe in the right cusp. Type III (3.5%): one cusp is located anteriorly, the other posteriorly and both coronary arteries arise from anterior cusp. Type IV (29.4%): Type III + raphe in the anterior cusp. Regarding to preoperative diagnosis, aortic stenosis dominated in Type I (78.8%) and aortic regurgitation dominated in Type IV (72.0%). Implanted valve sizes were 22.2 +/- 1.8 (Type I), 23.4 +/- 1.6 (Type II) and 24.0 +/- 2.2 (Type IV). There was a significant difference between Type I and Type II, same as Type I and Type IV. Babb's method and outflow measurement method were utilized to predict the aortic annular size. However, both of them were not reliable for estimating the size of the aortic annulus in cases of aortic stenosis undergoing AVR with a 21 mm prosthesis. PMID- 1613272 TI - [Clinical classification and surgical treatment of cor triatriatum]. AB - Twenty-one patients (age 35 days to 39 years) with cor triatriatum were treated surgically over a 17 year period at our institute. We define cor triatriatum as a congenital heart anomaly with the presence of an abnormal diaphragm that subdivides the left atrium into an accessory and a true left atrial chambers and that has "direct" hemodynamic communication between an accessory and a true left atrial chambers through one or more fenestration irrespective of accompaniment of an atrial septal defect or a partial anomalous pulmonary venous connection. By contrast with our findings of the hearts with cor triatriatum, every representative classification, such as Lucas-Schmidt's one, had some lack or duplication of the addressed types respectively. So we presented a clinical classification of cor triatriatum as follows: type I is the classical form with intact atrial septum, type IIa has an ASD between an accessory and a right atrial chambers, type IIb has an ASD between a right and a true left atrial chambers, and type IIc is a complexed form that has both communications of IIa's and IIb's. Of 14 typical cor triatriatum without isomerism nor other major complexed anomalies, 7 cases belonged to type I, and IIa 4, IIb 2, IIc 1 respectively. Of 7 so-called atypical cases, 5 cases belonged to type IIc and the rest two were unclassified complexed forms. Characteristically all of atypical cases had persistent left superior vena cava in common. 17 patients underwent total corrections and the rest 4 cases with single right ventricles underwent palliative operations for Fontan procedure in the near future. Transaccessory chamber approach for type I and IIb as the first choice provided ample exposure for complete excision of the obstructing membrane. Trans-right atrial approach were employed for closure of ASDs or for the other intraatrial partitions. Incision of the atrial septum should be avoided to prevent postoperative supraventricular arrhythmias if possible. There were no surgical death nor late death over 6 years follow-up period on the average. There existed some atypical cases that seemed very difficult to make differential diagnoses preoperatively, so careful surgical investigations into intraatrial anatomy should be made to perform proper corrections especially in the atypical cases. PMID- 1613273 TI - [Comparative study of anticoagulant management after coronary artery bypass surgery--warfarin versus dipyridamole]. AB - A prospective randomized study was performed in 137 coronary artery bypass surgery cases to determine if the administration of antiplatelet drugs would improve the patency of coronary artery bypass grafts. The warfarin group received warfarin and thrombotest was controlled to 20% or so. The dipyridamole group received both 300 mg of dipyridamole and 250 mg of aspirin orally each day. These two groups were compared for study in grafts patency. Results were analyzed by chi-square. In the warfarin group, 66 patients had three ITA-LAD grafts and 115 saphenous vein grafts (including 4 sequential grafts). In the dipyridamole group, 71 patients underwent 38 ITA grafts and 167 saphenous vein grafts (including 56 sequential grafts). Eighty-eight of the 107 grafts (82%) were patent in the warfarin group, and 190 of 205 grafts (95%) were patent in the dipyridamole group (p less than 0.01). Of the two ITA grafts in the warfarin group, no graft was occluded, a patency of 100%. In the dipyridamole group, 35 of 38 ITA grafts (92%) were patent. In the warfarin group, 86 of 105 saphenous vein grafts (82%) were patent. In the dipyridamole group, 155 of 167 saphenous vein grafts (95%) were patent (p less than 0.01). In the study of grafted coronary vessel, the patency of left anterior descending coronary artery, diagonal branch and right coronary artery was not significant between two groups. In the dipyridamole group, the patency of left circumflex coronary artery was 93%, and that of the warfarin group was 50% (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613274 TI - [Changes of immunity in the patients undergoing surgery for esophageal cancer]. AB - The kinetics of subpopulations and functional subsets of circulating immune cell, humoral antibody and complement were examined in the 18 patients undergoing surgery with thoracotomy and laparotomy for esophageal cancer. The following results were obtained. 1. Preoperative IgG-Fc-receptor (+) T cell (Tr cell) level was higher than normal level. 2. From 1st post operative day (1POD) to 14POD, WBC counts have increased, lymphocyte counts (especially T cell counts) have decreased significantly as compared with preoperative level. 3. In T cell subsets, counts of Tr cell have decreased significantly from 1POD to 3POD as compared with preoperative counts. 4. Counts of OKT8 positive cells (suppressor or cytotoxic T cell) and OKT4 positive cells (helper or inducer T cell) have decreased significantly from 1POD to 3POD as compared with preoperative count. OKT4/OKT8 ratio increased at 3POD (2.31 +/- 1.33). 5. In B cell subsets divided into using the type of cell surface immune antibody (sIgG, sIgA, sIgD), all subsets have decreased significantly as compared with preoperative counts. 6. Immune globulin (IgG, IgA, IgM, IgD) have decreased significantly from 1POD to 7POD, but at 14POD they increased significantly as compared with preoperative levels. 7. Complements (C3, C4) have decreased significantly from 1POD to 7POD. 8. The count of sIgG positive B cell had significant, negative correlation with carcinogenic factor and positive correlation with preoperative serum total protein. The other immune factors had no correlation with the factors before and during operation. These results suggest that cellular immunity of patients undergoing surgery with thoracotomy and laparotomy for esophageal cancer lose its autoregulation function especially in T cell, it does not recover until 14POD. PMID- 1613275 TI - [Surgical therapy of aortic regurgitation due to aortitis syndrome--effectiveness and extended indication of Bentall's operation]. AB - Fourteen patients with aortic regurgitation due to aortitis syndrome that underwent surgical therapy were studied with particular emphasis on the long term merits of Bentall's operations over the conventional valve replacement. They were divided into two groups; Group A: 6 aortic valve replacements (AVRs) and Group B: 8 Bentall's operations. Post operative complications related to aortitis syndrome developed in 3 cases; a case of paravalvular leakage (Group A) and two cases of aneurysm formation at the coronary artery anastomotic sites (Group B). We speculated that these complications were due to abnormal healing and recurrent inflammatory process of the disease. Therefore we think that conventional valve replacement is not suited to cope with these problems. Since 1984, we have adopted the policy to perform Bentall's operations for all patients with aortitis requiring valve replacement. Bentall's operation required longer aortic cross clamp time (212.1 +/- 53.9 min) than AVRs (73.0 +/- 25.0) and was more aggressive. However no patients with our current technique to reimplant the coronary artery button and distal graft to aorta anastomosis, which has been used since 1984, has developed pseudoaneurysm or valvular leakage. We conclude that our modified Bentall's operation is effective even for patients who have active aortitis syndrome or need redo operations. PMID- 1613276 TI - [Valve repair for mitral regurgitation due to ruptured chordae tendineae- repaired valve function and late results]. AB - Among 21 consecutive patients with significant mitral regurgitation due to ruptured chordae tendineae operated by an author (K.M.) between March, 1980 and August, 1990, the 18 patients who underwent mitral valve repair were studied to assess the repaired valve function and late results of the repair. The chordal rupture was due to idiopathic degenerative disease in 14 patients, infective endocarditis in three and trauma in one. Patients' ages ranged from 35 to 70 years (mean age 52). Nine patients were in New York Heart Association class II and the remaining nine in class III. In three patients with ruptured chordae of the anterior mitral leaflet, reconstruction of the chordae with xenograft pericardium was performed in two patients and partial closure of a commissure in one. In 15 patients with ruptured chordae of the posterior leaflet, Kay's repair was performed in 13 patients and leaflet resection technique in two. In addition to the chordal and leaflet repairs, Kay's mitral annuloplasty was performed in all. There was no hospital death and all patients showed significant hemodynamic improvement (systolic pulmonary arterial pressure from 43 +/- 20 mmHg preoperatively to 24 +/- 4 mmHg postoperatively, and pulmonary arterial wedge pressure from 17 +/- 10 mmHg to 6 +/- 3 mmHg, p less than 0.001 respectively). The repaired valves showed mild pressure gradient of 3.1 +/- 1.2 mmHg which was significantly lower than the gradient of 6.6 +/- 3.5 mmHg of SJM prostheses. Residual murmur was documented in six patients, in three of whom, however, the murmur disappeared within one year following the operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613277 TI - [Management of infective endocarditis]. AB - Clinical manifestations and the results of management of infective endocarditis were reported. Of 46 patients, 17 cases received medical treatment alone (group A), and 29 cases underwent surgical interventions (group B). Affected valves were aortic in 29, and mitral in 24. In group B, however, infection occurred on the aortic valve in 22, and on the mitral valve in 11. Aortic valve was more often affected in group B than in group A (p less than 0.05). Embolic complications were observed in 5 of group A, 4 of whom had involvement of cerebral vessels, and in 4 of group B, all of whom had cerebral emboli. Of 8 cerebral embolic episodes, 6 emboli originated from mitral valvular lesions. In group A, 6 (35.3%) died of cerebral accidents or acute heart failure within 30 days after the onset of illness. In group B, 20 cases were operated on at chronic stage, and 9 cases underwent operation at active stage. Various procedures, alleged to be the most favorable, were selected to the individual patient. No mortality was found in the former group, but one patient (11.1%) in the latter group died of multiple organ failure 31 days after surgery. All patients, who were operated on at active stage, received intravenous administration of antibiotics for 6 to 8 weeks after the operation. Comparing the actuarial survival rate of group A and group B, group B was superior to group A for initial 4 years, but no significant difference was discernible thereafter. PMID- 1613278 TI - [Assessment of left ventricular function with ESS-ESVI relationship in patients undergoing aortic valve replacement for aortic regurgitation]. AB - Aortic valve replacement (AVR) for aortic regurgitation (AR) results in the reduction of left ventricular dimensions. But postoperative death or congestive heart failure may occur in patients with left ventricular dysfunction. Pre- and postoperative stress (ESS)-volume (ESVI) relationship by M-mode echocardiography was examined in 30 patients undergoing AVR. Postoperatively, 23 patients (Group A) achieved a normal left ventricular dimension (LVDd less than 55 mm, LVDs less than 45 mm) and 7 patients (Group B) had persistent left ventricular dilation (LVDd greater than or equal to 55 mm, LVDs greater than or equal to 45 mm). Correlation between preoperative ESS and ESVI was significant (r = 0.92, p less than 0.001), and the ESS/ESVI was greater in Group A of 1.62 +/- 0.29 kdy/cm2/ml/m2 than in Group B of 1.18 +/- 0.19 kdy/cm2/ml/m2 (p less than 0.001). Three patients with ESVI greater than 180 ml/m2 and ESS/ESVI less than 1.2 kdyn/cm2/ml/m2 died after operation. Echocardiographic variables correlated with ESS/ESVI were ESVI (r = -0.57), FS (r = -0.53) and CSA (r = -0.47). The changes in LVDs (delta Ds) after AVR correlated with ESS/ESVI in 12 patients with severe left ventricular dilatation. Postoperative left ventricular function could be predicted by ESS-ESVI relationship by preoperative DBcAMP infusion test. ESS/ESVI is sensitive to changes in the left ventricular contractility. The patients with ESVI greater than 180 ml/m2 and ESS/ESVI less than 1.2 kdyn/cm2/ml/m2 may result in poor prognostic outcome. PMID- 1613279 TI - [Surgical managements of the compression of trachea and/or bronchus associated with congenital cardiovascular anomalies]. AB - From 1987 through 1990, 17 cases with tracheal and/or bronchial compression due to congenital cardiovascular malformations were experienced at our institutes. Respirator was required preoperatively in 10 patients (59%) due to severe respiratory symptoms by airway compression and narrowing. In all cases, bronchoscopy was carried out pre- or intra-operatively for the precise diagnosis and for the decision of operative procedures. Postoperatively 12 cases were successfully extubated and remained free of respiratory distress. We investigated the relationships among pre- and post-operative pressure ratio, preoperative flow ratio, requirement of preoperative respirator and indication for plication and suspension of pulmonary artery in the group of the patients, who had airway compression by the dilated pulmonary artery due to large left to right shunt. As a result of this investigation, these factors have no significant correlation. The severity of associated tracheomalacia might be a most susceptible cause, which required the preoperative managements with respirator and the surgical interventions to the dilated pulmonary artery. Infant with patent ductus arteriosus (PDA) could be surgically treated by the division of PDA through left lateral thoracotomy. If the left main bronchus shows complete obstruction after division of PDA, the additional surgical intervention like suspension of aortic arch is needed. Two cases were lost with reoperation and these suggested not only the priority of simultaneous repair of trachea and cardiovascular anomaly, but the necessity of minor intervention against adhesion (insertion of Gore-Tex sheet between suspended pulmonary artery and sternum) in the first-step palliative operation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613280 TI - [Surgical repair of infarct-related ventricular septal perforation using Teflon felt patch]. AB - Eight patients with infarct-related ventricular septal perforation underwent surgical repair using Teflon felt patch. The overall early operative mortality rate was 12% (1/8). One of three patients (33%) with cardiogenic shock preoperatively, one of five patients (20%) operated within 7 days after the onset of infarction died within 30 days after operation. A patient with inferior infarction died early after operation. In 5 of 8 patients (63%), IABP was removed within 24 hours after operation. A patient died due to the recurrence of gastric cancer in late postoperative phase. None of patients was found to have a recurrence of the ventricular septal perforation after the operation. Five of 6 patients (83%) surviving the operation are in NYHA class I or II. PMID- 1613281 TI - [Effects of coronary artery bypass grafting for patients with totally occluded left anterior descending arteries]. AB - Between April, 1987 and March, 1991, 21 patients with totally occluded left anterior descending arteries (TOLAD) underwent coronary artery bypass grafting (CABG) in our institute. All of them were diagnosed as angina pectoris and 15 (71%) of them have had episodes of myocardial infarction. Graftability of TOLAD was 90% (19/21) and two of the TOLADs were not suitable for CABG because severe atherosclerosis of these arteries were observed intraoperatively. There was no operative death. Short term (1-2 months) patency was 64% (7/11) for saphenous vein grafts (SVG) and 100% (8/8) for left internal thoracic artery grafts (LITA). Left ventricular wall motion assessed by left ventriculography showed impaired regional wall motion in 63% segments of the segment #2, #3 and #6 preoperatively. However, the regional wall with impaired motion decreased to 31% after CABG. Thallium-201 scintigraphy showed impaired perfusion in 62% segments of the left anterior wall, apex and interventricular septum preoperatively. However, the regional wall with impaired perfusion decreased to 42% after CABG. Exercises tolerance assessed by treadmill test was improved from 3.8 +/- 0.7 Mets preoperatively to 6.5 +/- 0.7 Mets with patent coronary bypass grafts. These data suggested that CABG can improve the wall motion of the regions perfused by TOLADs and the LIMA is more suitable than the SVG for CABG to TOLAD. PMID- 1613282 TI - [The effects of sodium concentration in reperfusion solution upon myocardial protection]. AB - The effects of several sodium concentrations in reperfusion solution (RS) were studied. Experimental time course was as follows: 20 min working perfusion, 3 min cardioplegic infusion with St. Thomas Cardioplegic Solution followed by global ischemia for 33 min at 37.5 degrees C, 15 min early Langendorff reperfusion with various sodium concentrations modified with Krebs Henseleit Bicarbonate Buffer (KHBB) and 5 min late reperfusion with KHBB, followed by 20 min working perfusion. Percent recoveries of aortic flow and Creatine Kinase leakage showed that 110 mM sodium of RS possessed optimal protective properties with bell shaped dose response characteristics. PMID- 1613283 TI - [Traumatic rupture of the diaphragm--a case of lung herniation into the abdominal cavity]. AB - A first case of lung herniation into abdominal cavity with traumatic diaphragmatic rupture is described. A 41-year-old Japanese man with chronic obstructive pulmonary disease suffered traumatic diaphragmatic rupture. He needed to get continuous mandatory ventilation for a long time. At the time of operation, left lung herniation into the abdominal cavity was observed. When those who have chronic obstructive pulmonary disease suffered thoraco-abdominal injury, we should take care that pulmonary herniation might exist. PMID- 1613284 TI - [Corrected transposition of the great arteries with associated tricuspid valve incompetence--report of a case of successful tricuspid valve replacement]. AB - A 36-year-old woman with corrected transposition (C-TGA) of great arteries with associated systemic atrioventricular valve (A-V valve) regurgitation was presented. Cineangiography revealed that the right sided ventricle was morphologic left ventricle, and left sided ventricle was morphologic right ventricle. In addition, severe systemic A-V valvular regurgitation (Sellers IV) was demonstrated. Under the diagnosis of C-TGA with associated A-V valvular regurgitation, left sided atrioventricular valve replacement was performed using 29 mm SJM valve. Left sided atrioventricular valve was tricuspid valve (TV). A part of the anterior tricuspid leaflet and two pieces of papillary muscle was resected. Postoperative course was uneventful. The pathological findings indicated that valvular tissue had myxomatous degeneration. PMID- 1613285 TI - [Separate perfusion of upper and lower body for ruptured thoracoabdominal aortic aneurysm--a case report]. AB - A case of ruptured thoracoabdominal aortic aneurysm was presented. The patient had emergent replacement of thoracoabdominal aorta with an aid of separate perfusion of upper and lower body. The postoperative course was uneventful. It was suggested that separate perfusion of upper and lower body was useful in the patients who require extensive aortic replacement and who are at substantial risk for spinal cord injury. PMID- 1613286 TI - [A case of unknown origin cancer of the mediastinal lymph node]. AB - We encountered an unusual case with a sole cancer focus at the mediastinal lymph node. The patient was a 44-year-old man who visited our department with a chief complaint of chest pain. Subsequent chest X-ray and CT revealed an enlargement of a mediastinal lymph node. The excised lymph node measured 6.8 x 5.5 x 4.0 cm and weighed 51 g. It showed metastasis of poorly differentiated adenocarcinoma. In spite of a thorough systemic examination, no primary foci were detected. Lymph node tumors of the mediastinum or hilar region with unknown primary foci are extremely rare (there have been only 2 reported cases of lesions found at the hilar lymph node with unknown primary focus). There have been no reports on cancerous foci limited to the mediastinal lymph nodes. The patient has been under chemotherapy and radiotherapy during the past 3 years following surgery. He shows no signs of recurrence. It is a very unusual case. A possible classification of T0N2M0 has been considered. PMID- 1613287 TI - [Emergent cardiovascular operation in patients older than 75 years]. AB - From January 1988 through December 1990, 7 patients older than 75 years underwent emergent cardiovascular operation. We evaluated those operative results. The mean age was 80.1 years (range 77 to 85 years) and there were 5 men and 2 women. Coronary artery bypass grafting for 2 cases, closure of ventricular septal perforation for 1 case, graft replacement of ascending aorta and suspension of aortic valve in 2 cases, closure of left ventricular free wall rupture (LVFWR) in 1 case and closure of arch aneurysm rupture for 1 case were performed. Operative mortality was 14.3% (1/7). There was one hospital death. Five survivors had uneventful course in early postoperative term, but they needed long elaborate hospital care because of complications in noncardiac general organs in late postoperative term. They need nutritional support, rehabilitation for muscle weakness and so on. Their mean postoperative hospital period was 53 days. All of them were improved in New York Heart Association I or II. We concluded that we attained a good operative result in emergent cardiovascular operation in patients older than 75 years by effective operation as a result of long elaborate postoperative hospital care. PMID- 1613288 TI - [Surgical analysis of mediastinal lymphangioma--analysis of 7 cases]. AB - Mediastinal lymphangioma is a very rare disease. In this study, we evaluated 7 surgically treated cases of mediastinal lymphangioma. Four males and 3 females with ages ranging from 5 months to 74 years (average 31.4 years) were examined. Four patients were asymptomatic but had abnormal shadows on their chest X-ray. Of the remaining patients, one had hoarseness and another had superior vena cava syndrome and both had dyspnea. The other patient was discovered because of cervical tumor. Multiple lymphangiomas were found in only 2 patients. One patient had 4 tumors and the other had 2 tumors in the mediastinum. Of all lymphangiomas, 2 were found in the superior mediastinum, 2 in the anterior mediastinum, 3 in the median mediastinum and 3 in the posterior mediastinum. All patients had cystic lymphangioma including 1 with capillary lymphangioma and 1 with cavernous lymphangioma. Median sternotomy was performed in 3 of the patients and posterolateral thoracotomy was performed in the remainder. The cervical tumor was removed by local incision. Complete resection of the lymphangiomas was performed and no recurrence was observed after surgery. PMID- 1613289 TI - [Surgical treatment of myasthenia gravis associated with Graves's disease]. AB - During past 30 years, we experienced 253 patients who underwent surgery for myasthenia gravis. Among these patients, 9 were associated with Graves' disease. No patients had thymoma. Five patients underwent thymectomy after they had become euthyroid by medical treatment, though four patients required subtotal thyroidectomy before thymectomy. One patient developed myasthenic crisis following thyroidectomy and was treated with respirator for 5 days. But thymectomy was performed without myasthenic crisis in these four patients between 25 days and 60 days after thyroidectomy. They have been doing well and no see-saw phenomenon was presented. Thymectomy is safe and effective even in the patients with Graves's disease, and we recommend to perform it after they become euthyroid by medical or surgical treatment. PMID- 1613290 TI - [A case of delayed ascending aortic pseudoaneurysm after traffic injury mimicking cardiac tumor]. AB - A 44-year-old man was transferred to our hospital because of severe congestive heart failure complicated with acute renal failure and hepatic failure. He had been injured in a traffic accident three years before. Echocardiogram demonstrated a large tumor on the anterior wall of right ventricle obstructing RV outflow. Emergent operation was performed with cardiopulmonary bypass. Tumor was too large and invading into RV endocardium partially. RV patch enlargement was performed because it was impossible to resect tumor entirely. CVP was decreased dramatically to 8 cmH2O from 28 cmH2O. Postoperative hemodynamic was stable, but patient died of hepatic failure. Autopsy revealed that tumor was pseudoaneurysm from ascending aorta and ruptured into right ventricle. PMID- 1613291 TI - [Pneumonectomy in a case of chronic hemodialysis]. AB - A 60-year-old male was referred to our hospital due to a well-delineated tumor (4 x 4 x 3 cm) in the left hilar region demonstrated by chest X-ray examination. Bronchofiberscopic biopsy showed evidence of well moderately differentiated epidermoid carcinoma. Since the tumor infiltrated to a part of the pericardium, left pneumonectomy and partial resection of pericardium were performed. The disease was p-T2, N1, M0, and state II. Anemia was corrected with Erythropoietin, and hemodialysis was performed for 3 consecutive days before operation. Hemodialysis 3 times per week was initiated from 2 days after operation. Hyperkalemia was successfully treated by GI therapy (continuous intravenous infusion of glucose+insulin). His postoperative course was good without bleeding and infection. He was discharged 37 days after operation and has been observed on an outpatient basis. With an increased and aging patients on chronic hemodialysis, the operations for various malignant tumors have been increasing. However, there are few reports on operation for lung cancer and no report on pneumonectomy in such patients in Japan. We performed pneumonectomy for lung cancer detected in a patient on chronic hemodialysis for 4 years and obtained good results. PMID- 1613292 TI - [Pulmonary lymphangiomyomatosis associated with spontaneous pneumothorax]. AB - A 34-year-old female associated with spontaneous pneumothorax was diagnosed as pulmonary lymphangiomyomatosis by open lung biopsy and pathological examination. The biopsy specimen of the lung showed marked proliferation of smooth muscle in the lung. This disease is seen only in women in childbearing age, and hormonal therapy is ineffective, but bilateral oophorectomy seems, in some cases, to have a beneficial effect. Lung transplantation can be applied to patients with terminal pulmonary lymphangiomyomatosis. PMID- 1613293 TI - [A case of tricuspid valvular myxoma in a child]. AB - A six-year old boy had hospitalization because of cardiac murmur and syncope attack. Laboratory data including immunoglobulin and erythrocyte sedimentation rate were normal, but echocardiography and cardioangiography indicated tricuspid valvular myxoma in the right atrium. The tumor was successfully removed with the septal tricuspid valve using the cardiopulmonary bypass. The tumor was 18 x 20 x 12 mm in size and pathological findings showed a myxoma originated from tricuspid valve. Now he shows normal cardiac function and no recurrent sign of tumor. There has been reported a few cases of valvular myxoma in Japan. However, this is the first case which was successfully resected by surgery. PMID- 1613294 TI - Defecatory disorders, anorectal and pelvic floor dysfunction: a polygamy? Radiologic and manometric studies in 41 patients. AB - A consecutive series of 41 patients with defecatory disorders was prospectively studied by anal manometry and evacuation proctography to determine the relationship between abnormalities and symptoms. The patients (29 female, 12 male, aged 41 +/- 2.3 years) all complained of difficulty in evacuation. All had normal colonoscopy and biochemistry. There was no evidence of megacolon or megarectum, and no symptoms had been previously treated by pelvic floor surgery. All subjects completed detailed questionnaires related to gastrointestinal symptoms with special reference to excessive straining and discomfort, digital manipulations during defecation, a sense of pelvic heaviness and incomplete evacuation. Each patient underwent clinical examination, anal manometry and defecography during a single outpatient visit. Rectocele (16 patients) was significantly associated with vaginal digitation, lower stool frequency, delayed rectal emptying and decreased rectal sensation to distension. Increased anal pressure on straining (14 patients) was also related to a poor rectal emptying in 13 patients. Neither perineal descent (24 patients) nor external rectal prolapse (12 patients) was related to objective obstruction. Nevertheless there was an association with pelvic heaviness and lower anal manometric recordings. Five among 16 patients with rectocele had manometric anismus. Forty percent of patients with intussusception also had a paradoxical sphincter response during defaecation. Furthermore, associated abnormalities were extremely common (34 of 41 patients), accurate interpretation of which was necessary for planning effective therapy. PMID- 1613295 TI - Anal fissure: correlation between symptoms and manometry before and after surgery. AB - The study compared symptoms and manometric results in 76 patients (42 men and 34 women; median age: 45 years) before and at long-term follow-up (median time: 54 months) after fissurectomy with posterior midline sphincterotomy for anal fissure. The fissure healed in all cases. Sporadic loss of continence for flatus or for liquid stool occurred in 21 patients (27.6%) and soiling was present in 7 other patients (9.2%). Preoperative maximum resting anal pressure was significantly greater in the study group compared with 40 control subjects (p less than 0.001). Postoperative resting anal pressure fell significantly (p less than 0.001) and remained low on long-term assessment. Postoperative maximal squeeze pressure remained unchanged. No correlation could be found between preoperative and postoperative clinical symptoms (including continence) and anorectal manometry. PMID- 1613296 TI - Multiple rubber band ligation after one loading of instrument. PMID- 1613298 TI - Endoscopic crescentic fold disease of the sigmoid colon: the clinical and histopathological spectrum of a distinctive endoscopic appearance. AB - In this paper we describe an endoscopic appearance of the sigmoid colon characterised by mucosal swelling, erythema and haemorrhage strictly localised to the crescentic mucosal folds. In a 5-year period these changes were seen in 34 (1.42%) of 2380 colonoscopies and fibreoptic sigmoidoscopies. The majority of patients were middle-aged or elderly. Diverticular disease was present in most (82%) but the abnormalities were confined to the crescentic mucosal folds with sparing of the diverticular orifices. The majority of patients presented with a history of bleeding per anum. Histologically there was a spectrum of changes varying from minor vascular congestion to florid active inflammatory disease with crypt architectural abnormalities mimicking ulcerative colitis, but rectal biopsies were invariably normal. Three patients later progressed to typical distal ulcerative colitis and two other patients presenting to us with endoscopic crescentic fold disease had a previous histologically documented history of distal ulcerative colitis. In three patients the histological features were of mucosal prolapse. About half the patients required some form of therapy to control their symptoms. Steroids and/or sulphasalazine were of value although two patients subsequently underwent sigmoid resection, one to control bleeding and the second for a diverticulosis-associated stricture. Whilst endoscopic crescentic fold disease represents a specific endoscopic appearance the clinical and histological features indicate a wide spectrum of disease. PMID- 1613297 TI - Symposium on constipation. PMID- 1613299 TI - Results of stoma formation for idiopathic megarectum and megacolon. AB - Bowel resection for idiopathic megarectum and megacolon does not always predictably relieve symptoms and has a significant morbidity. We have therefore evaluated the results of stoma formation in this condition. All patients had a bowel frequency of less than one per week, and all had a dilated rectum or colon. Eight patients, six of who had had a previous unsuccessful operation for their constipation, had a colostomy--this relieved the constipation and the need for laxatives in all six patients with rectosigmoid dilatation, although one patient could not tolerate his stoma. Two patients with dilatation of the whole colon were not helped. An ileostomy was formed in four patients with previous colonic resection, with relief of constipation in all. However pain and abdominal distension were common persistent symptoms in both groups. Four patients with a colostomy and all four patients with an ileostomy felt subjectively improved with a stoma. Stoma formation is a viable alternative to more major surgery, either as a primary procedure or after previous surgery has failed. PMID- 1613300 TI - Age-related alterations in the strength and collagen content of left colon in rats. AB - The biomechanical properties and intestinal wall composition of left colon were studied in 4-month-old, 14-month-old, and 27-month-old male rats. The hydroxyproline content and hydroxyproline concentration in old rats were increased by 36% and 26%, respectively, compared with young rats and by 20% and 17%, respectively, compared with middle-aged rats. In middle-aged rats the maximum load increased by 21%, compared with young rats. In old rats, however, the maximum load decreased by 13%, compared with middle-aged rats. Histological examination showed that the mean crypt height was 9% higher in middle-aged rats and 12% higher in old rats than in young rats. In conclusion, an accumulation of collagenous proteins was found in old rats compared with middle-aged rats and this was accompanied by a decrease in the strength, which may deteriorate the functional integrity of the left colonic wall with age. PMID- 1613302 TI - ECG of the month. Three little words. Sustained bigeminal rhythm. PMID- 1613301 TI - Paradoxical sphincter reaction and associated colorectal disorders. AB - Of 71 patients with paradoxical sphincter reaction, 54 had symptoms of constipation or outlet obstruction and 17 were incontinent. The patients were investigated with defecography, colon transit time, anorectal manometry and electromyography. Ninety-six percent of the patients had additional changes in anorectal anatomy and physiology; 70% of the patients had abnormal defecography and 42% had delayed colon transit time. Decreased maximal anal pressure (MAP) and maximal squeeze pressure (MSP), indicating impaired function of the anal sphincters might be one reason for incontinence in patients with paradoxical sphincter reaction. The paradoxical reaction occurred in the puborectalis muscle and in three tested sites in the external sphincter. It is sufficient to record the EMG activity in one muscle and at one point to diagnose a paradoxical sphincter reaction. The absence of a normal closing reflex on electromyography is evidence for a paradoxical sphincter reaction. Denervation was more pronounced in the external sphincter than in the puborectalis muscle. The right pudendal nerve was subjected to damage more often than the left nerve. PMID- 1613303 TI - Relapsing polychondritis. AB - Relapsing polychondritis is a rare disease of unknown etiology. It is characterized by progressive episodic recurring inflammation and degeneration of cartilaginous structures. The inflammation typically involves the cartilage of the ear, nose, trachea, and various peripheral joints. Treatment options most commonly involve the use of anti-inflammatory drugs and corticosteroids. PMID- 1613304 TI - Cancer in south Louisiana. Part 1: Tobacco-related cancers. AB - Tobacco-related cancers comprise about one third of the newly-diagnosed cancer in South Louisiana. These cancers are three times more common in men than in women. For cancers originating from anatomic sites where there is a direct contact with tobacco, ie, lung, larynx, oral cavity and pharynx, and esophagus, incidence rates for blacks are either higher than or similar to the rates for whites. For cancers of the bladder and the kidney, sites which have no direct contact with tobacco products, incidence rates are higher in whites than blacks. In general, white men in South Louisiana tend to have risks significantly higher than national for tobacco-related cancers, in particular, cancers of the lung (31% higher) and the larynx (42% higher). A similar pattern is observed for white females but is less pronounced. Black men in South Louisiana, on the other hand, have significantly lower rates than the SEER averages for cancers of the esophagus, oral cavity, and pharynx. Risks for other tobacco-related cancers are very comparable. There are very small differences in rates for black women between South Louisiana and SEER areas. Tobacco-related cancers are most preventable. Any effective cancer program in Louisiana must emphasize prevention and cessation of tobacco use. PMID- 1613305 TI - Meeting the needs of special populations: a formative evaluation of a school based smoking prevention program. AB - The National Cancer Institute has recommended three minimum components for school based smoking prevention programs: short-term physiological effects, social consequences, and refusal skills. This investigation compares these minimum components with participant evaluations of the usefulness of content areas of a prevention program. Three hundred 9th grade students participated in the study. Results indicate that Health Hazards, Nonsmokers' Rights, Decision-Making Skills, and Peer Influences were most often rated as "Very Helpful" in resisting pressures to smoke. Assessment of initial knowledge of the health hazards and consequences associated with tobacco use indicate that 77% of the students received a "D" or lower. Results suggest that this group of adolescents, who are at risk for becoming adult smokers, may not be adequately served by public information sources and may therefore benefit from the inclusion of an additional minimum component: information about the long term health consequences associated with smoking. PMID- 1613306 TI - Cancer in Louisiana: a public health perspective. PMID- 1613307 TI - Cancer in south Louisiana. Part II: Gastrointestinal tract cancers. AB - Incidence rates for the most common cancers of the gastrointestinal tract are presented for the 5 geographic regions in South Louisiana for the period 1983 1986. The risk of colorectal cancer, the most frequent GI cancer in males and females, is uniformly lower in these regions of South Louisiana than in other areas of the United States. Gastric cancer rates are significantly high in black males, as are pancreatic cancer rates in whites of both sexes compared to national rates. PMID- 1613308 TI - The breast cancer prevention trial. PMID- 1613309 TI - Cancer in south Louisiana. Part III: Cancers of the breast and the reproductive system. AB - Cancers of the breast and reproductive system are less common in South Louisiana than other parts of the nation. The only exception is invasive cervical cancer. Incidence rates for breast cancer in South Louisiana women are 20% lower than the SEER combined rates, and rates for cancer of the uterine corpus and the ovary among white women are 43% and 32% lower respectively than the SEER averages. South Louisiana men also have risks 14% (whites) and 30% (blacks) less than the national of developing prostatic cancer. These significantly low rates are observed for all regions in South Louisiana. The reasons for the low rates are not clearly understood. Possible explanations include: less frequent use of cancer screening tests, high prevalence of hysterectomy, lower risk exposures, and host/genetic factors. The low incidence rates for these cancers are not accompanied by more favorable mortality outcomes, suggesting a poorer survival among Louisiana cancer patients partially due to late stage disease at the time of diagnosis and treatment. Programs to increase the accessibility of cancer screening tests and improve early detection are greatly needed. PMID- 1613310 TI - Ocular trauma in otolaryngology. AB - Otolaryngologists are commonly called upon to emergently evaluate blunt trauma to the facial skeleton. These injuries are occasionally associated with serious trauma to the orbital contents. This manuscript reviews these orbital injuries by considering the pertinent eye anatomy and the extensive examination usually performed by an ophthalmologist. Anterior and posterior segment injuries along with specific trauma to the optic nerve will also be discussed. PMID- 1613311 TI - A rationale for the use of percutaneous transluminal angioplasty in the setting of acute myocardial infarction. AB - Rapid reperfusion of infarcting myocardium has become a cornerstone of modern medical care. The role of percutaneous transluminal coronary angioplasty (PTCA) in this treatment of acute myocardial infarction is not clear. PTCA is effective in the early hours of MI as primary reperfusion therapy, in lieu of thrombolysis. Arterial patency using this strategy is excellent with low complication rates, and this therapy is comparable and may be superior to thrombolysis when myocardial performance and recurrent ischemia are considered. PTCA is the treatment of choice for the patient in whom thrombolysis is contraindicated, or who develops cardiogenic shock. The role of angioplasty as secondary therapy for myocardial infarction after pharmacologic thrombolysis and reperfusion is controversial. The evidence is clear that immediate PTCA after successful thrombolysis is not warranted. The decision for elective angioplasty after successful or unsuccessful thrombolysis should probably be judged on a case to case basis. PMID- 1613312 TI - Thrombolytic therapy in acute myocardial infarction: an overview. AB - Several drugs are now available for thrombolysis in acute myocardial infarction. These drugs have unique properties and modes of action in the clotting pathway which may cause reperfusion of the infarct-related vessel resulting in preservation of viable myocardial tissue. Critical factors for thrombolysis include: time intervals for administration, patient inclusion criteria, and the necessity for more frequent administration in patients eligible for thrombolytic therapy. PMID- 1613313 TI - The electrocardiogram in the diagnosis of acute myocardial infarction. AB - Diagnosis of acute myocardial infarction as early in the course of its evolution as possible is an important requirement for successful coronary reperfusion. In spite of the availability of many newer diagnostic methods, electrocardiography retains its preeminent place in the diagnosis of acute myocardial infarction. The value and limitations of the electrocardiogram in the diagnosis of acute myocardial infarction are reviewed. PMID- 1613314 TI - Cardiac rehabilitation: an overview. AB - This article provides an overview of the process and application of cardiac rehabilitation following myocardial infarction and coronary artery bypass grafting. The authors discuss risk factor modification targeting smoking, serum cholesterol, hypertension, and exercise training. The role of the physician and the practitioner are addressed as well as the physiological and psychological benefits of cardiac rehabilitation. PMID- 1613315 TI - Is the antiphospholipid syndrome caused by antibodies directed against physiologically relevant phospholipid-protein complexes? PMID- 1613316 TI - Effects of lovastatin and gemfibrozil on high-density lipoprotein subfraction density and composition in patients with familial hypercholesterolemia. AB - The effects of gemfibrozil and lovastatin treatment on composition and hydrated density distribution of high-density lipoprotein (HDL) were studied in 21 patients with heterozygous familial hypercholesterolemia with the use of HDL density gradient ultracentrifugation. At baseline the patients with familial hypercholesterolemia had a markedly reduced or missing HDL2 subfraction and their HDL3 was more dense with reduced content of cholesteryl ester and increased content of triglyceride compared with HDL of control subjects with normal lipid values. Gemfibrozil and lovastatin caused primarily similar alterations in HDL components in HDL2 and HDL3 subfractions. Both agents increased apolipoprotein AI and apolipoprotein AII concentrations significantly in HDL2, whereas the apolipoprotein changes in HDL3 were relatively smaller. The difference between the effects of these two agents was related to the HDL lipid composition. Gemfibrozil increased the cholesterol concentrations of HDL2 and HDL3 (p less than 0.05 for both), and lovastatin caused significant increases in HDL2 (p less than 0.05) and HDL3 phospholipids (p less than 0.01). The observed similarity of qualitative alterations in HDL subfractions produced by these two agents in patients with familial hypercholesterolemia differs from those reported in other types of hyperlipidemia and is probably a consequence of the basic abnormalities in HDL that are characteristic of familial hypercholesterolemia. PMID- 1613317 TI - A kinetic study of factor I-mediated modification and release of RBC-bound DNA anti-DNA immune complexes. AB - A tritiated DNA-anti-DNA complement--containing immune complex probe was used to define the mechanism of factor I-mediated modification and release of erythrocyte CR1-bound immune complex in 10 normal control subjects. Experiments were performed with preformed immune complex, autologous erythrocytes, and autologous serum. Control experiments were performed by using a single donor source of erythrocytes and commercial factor I. The data demonstrate that the modification release rate was first order with respect to factor I concentration, the mean half-life of red blood cell-bound immune complex was 1.7 +/- 0.7 minutes, and the mean percent of total immune complex present as unbound complexes was 19 +/- 11. These data are consistent with a clearance model in which factor I-mediated modification and release of red blood cell-bound immune complex plays a significant role in immune complex handling. PMID- 1613318 TI - Depletion of plasminogen in vitro or during thrombolytic therapy limits fibrinolytic potential. AB - Thrombolytic therapy frequently induces a "lytic state" associated with a decrease in plasma plasminogen concentration that could limit therapeutic efficacy. We therefore investigated the influence of soluble plasminogen concentration on in vitro lysis of retracted whole-blood clots in plasma from normal subjects and from patients undergoing thrombolytic therapy. With recombinant tissue plasminogen activator (1000 ng/ml) or two-chain urokinase plasminogen activator (250 U/ml), minimal clot lysis occurred in normal plasma depleted of plasminogen by lysine Sepharose chromatography. Clot lysis induced by two-chain urokinase plasminogen activator increased progressively in normal plasma at initial plasminogen concentrations between 0.06 to 6 U/ml, whereas maximum lysis with recombinant tissue plasminogen activator occurred between 0.5 U/ml and 1 U/ml and was less at lower and higher concentrations of plasminogen. Incubation of whole-blood clots in normal plasma with recombinant tissue plasminogen activator resulted in little change in plasminogen concentration during 6 hours, with a constant rate of clot lysis. Incubation with two-chain urokinase plasminogen activator, however, caused a rapid decrease in plasminogen concentration and a corresponding decrease in lysis rate; lysis rate was restored after repletion with purified plasminogen. The effect of in vivo activator induced plasminogen depletion on in vitro clot lysis rates was tested with plasma obtained from patients 90 to 120 minutes after they had received 30 mg of acylated plasminogen-streptokinase activator complex that showed depletion of plasminogen to 14% +/- 2%. These plasma samples produced only 4% +/- 1% in vitro clot lysis during 4 hours but lysis increased progressively after repletion with 1, 2, and 4 U/ml plasminogen.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613319 TI - Comparative ultrastructure of the tip of ventricular papillary muscle. AB - Electron microscopic studies of the tips of left ventricular papillary muscles from seven human, two monkey, three sheep, and two chicken hearts were done to elucidate the fine structure of myotendinous junctions. The human specimens were from normal hearts obtained 3 to 9 hours postmortem from persons aged 7 months to 30 years (mean, 13.3 years). We found no significant ultrastructural differences between the human hearts and those of monkey, sheep, and chicken. Myocardial fibers were elongated and thinner (tapered) in the tips of papillary muscles. In addition to usual working myocardial cells, the distal end of narrowing muscle fibers also contained small pale cardiocytes containing fewer myofibrils and smaller mitochondria. These cells were similar to P cells or transitional cells in the conduction system. Nerve axons and Schwann cells were commonly seen in the interstitium, usually in association with capillaries. Fibroblasts and axon varicosities were occasionally seen extremely close to the cardiocytes. These specialized myocardial cells associated with rich neural tissue in the papillary muscle tip possibly function as foci of local automaticity. This histologic organization may also represent neurosensory function responding to and monitoring local pressure changes, efferent adrenergic or cholinergic neural activity, or both. PMID- 1613320 TI - Effects of methyl acetyl phosphate, a covalent antisickling agent, on the density profiles of sickle erythrocytes. AB - Methyl acetyl phosphate specifically acetylates valine-1, lysine-82, and lysine 144 in the 2,3-diphosphoglycerate binding cleft of hemoglobin S, thereby inhibiting its gelation (greater than 32 gm/dl) at pH 7.4. To extend these findings, the effect of methyl acetyl phosphate on the density of sickle cells has been evaluated by phthalate ester gradient centrifugation and by Larex Percoll density centrifugation. After treatment with methyl acetyl phosphate (40% modification of the intracellular hemoglobin S), oxygenated sickle erythrocytes had a lowered density profile, as measured in a phthalate ester gradient. Thus 83% of untreated oxygenated sickle cells had densities greater than 1.098 gm/ml, whereas after treatment with methyl acetyl phosphate, 52% of the cells were in this density range. Under anaerobic conditions, methyl acetyl phosphate was even more effective in lowering cell density. For example, 50% of untreated deoxygenated cells had densities greater than 1.098 gm/ml, but none of the cells treated with methyl acetyl phosphate were this dense. For studies with Larex Percoll density gradients, sickle erythrocytes were first separated into two fractions (densities greater than and less than 1.1 gm/ml) by Percoll-Hypaque centrifugation. The amount of oxygenated sickle cells exhibiting densities greater than 1.074 gm/ml decreased by about 32% on treatment with methyl acetyl phosphate. For deoxygenated sickle cells, treatment with methyl acetyl phosphate resulted in an average decrease of approximately 24% in the number of cells with densities greater than 1.074 gm/ml.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613321 TI - Sex- and strain-related differences in megakaryocytopoiesis and platelet production in C3H and BALB/c mice. AB - In an effort to explain the different platelet production capabilities of male and female mice, megakaryocyte and platelet indices were measured on castrated male and oophorectomized female C3H and BALB/c mice, along with suitable intact controls. In agreement with our previous work, intact male BALB/c mice had higher platelet counts and percent incorporation of sulfur 35 into platelet values than did intact female BALB/c mice. Also, both intact BALB/c and C3H male mice had higher platelet counts than their castrated counterparts. Fewer femoral megakaryocytes were found in intact BALB/c and C3H male mice than in their female counterparts (p less than 0.05), but only BALB/c male mice had larger megakaryocytes than BALB/c female mice (p less than 0.0005). Castration caused increased numbers and decreased sizes of megakaryocytes (p less than 0.05) in both strains of mice, but oophorectomy did not change the characteristics of megakaryocytes in these mice. In all treatment groups, C3H mice had megakaryocytes with higher average deoxyribonucleic acid content than did BALB/c mice (p less than 0.0005), that is, BALB/c mice had greater percentages of 8N and 16N megakaryocytes than did C3H mice, but C3H mice had higher proportions of 32N and 64N megakaryocytes than did BALB/c mice (p less than 0.05 to p less than 0.0005). Although a difference in megakaryocyte ploidy was not detected between intact male and intact female C3H mice, BALB/c female mice had elevated percentages of low ploidy classes (8N) when compared with BALB/c male mice (p less than 0.005). Intact male C3H mice had higher percentages of 16N megakaryocytes (p less than 0.05) than did their neutered counterparts.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613322 TI - Glucocorticoids and mineralocorticoids: antifibrotic and profibrotic components of wound healing. PMID- 1613323 TI - Acetaldehyde measurement in RBCs: potential new marker for alcohol abuse. PMID- 1613324 TI - Strange brew: the politics and ethics of fetal tissue transplant research in the United States. PMID- 1613325 TI - Method of acetaldehyde measurement with minimal artifactual formation in red blood cells and plasma of actively drinking subjects with alcoholism. AB - After alcohol consumption, a substantial amount of acetaldehyde that is reversibly bound to protein and nonprotein components of the red blood cells circulates in the blood and could cause extrahepatic toxicity. However, acetaldehyde measurement in human red blood cells is hampered by considerable ex vivo artifactual formation as a result of nonenzymatic oxidation of ethanol during protein precipitation. To eliminate this source of artifactual formation, free and reversibly bound acetaldehyde were trapped with semicarbazide from red blood cell hemolysates, and both the stroma and the hemoglobin were sequentially removed by centrifugation and ion-exchange chromatography in carboxymethyl Sephadex, respectively. The eluted semi-carbazone was dissociated with perchloric acid, and the acetaldehyde that was released in the protein-free supernatants was measured by head-space gas chromatography. Maximal retention of hemoglobin by carboxymethyl Sephadex and complete recovery of acetaldehyde and ethanol were achieved at a pH of 5.3. The artifactual formation decreased from 2.62 +/- 0.32 mumol of acetaldehyde per millimole of ethanol in the initial hemolysates to 1.38 +/- 0.20 mumol after removal of the stroma and to a level that is comparable to measurements in plasma (0.09 +/- 0.02 mumol) after removal of both the stroma and the hemoglobin. In 12 actively drinking subjects with alcoholism, with blood ethanol levels that ranged between 9 and 81 mmol/L, the concentrations of acetaldehyde in red blood cells (11.50 +/- 1.46 mumol/L; range: 7.5 to 22 mumol/L) were minimally affected by blood ethanol levels and were three times as high as those in the plasma (3.74 +/- 1.49 mumol/L).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613326 TI - Eicosanoids: potential regulators of extracellular matrix formation in the kidney. PMID- 1613327 TI - Acetaldehyde-modified hemoglobin as a marker of alcohol consumption: comparison of two new methods. AB - We examined the diagnostic value of acetaldehyde-hemoglobin adducts in the detection of heavy drinking and alcoholism. Acetaldehyde adducts from red cells were measured by new chromatographic and immunologic methods. The study population included 20 men with well-documented histories of chronic alcoholism, 18 men who were heavy drinkers, 22 male healthy control subjects, and 8 control subjects with liver disease that was not related to alcohol use. In addition, 20 healthy volunteers and 5 control subjects participated in the study to determine the effect of an acute dose of ethanol. The results that were obtained by the two new methods correlated significantly (r = 0.38, p = 0.002). With both methods, the concentrations of acetaldehyde-hemoglobin adducts were found to be significantly higher in red cells of heavy drinkers (p less than 0.001) and subjects with alcoholism (p less than 0.001) when compared with control subjects. Acetaldehyde-modified hemoglobins appear to have at least the same sensitivity (chromatographic determination = 50% and immunologic determination = 50%) to detect heavy drinking as the most widely accepted conventional biochemical markers of alcohol abuse, gamma-glutamyltransferase (39%) or mean corpuscular volume (17%). In a group of 20 healthy volunteers, acetaldehyde-hemoglobin adducts increased significantly even after a single high dose of ethanol (2 gm/kg), whereas there was no change in the conventional markers of alcohol consumption at the same time. Acetaldehyde-hemoglobin adducts assays should be useful for the detection of heavy drinking in clinical settings. PMID- 1613328 TI - Thromboxane A2 regulates protein synthesis of cultured human mesangial cells. AB - Cultured human glomerular mesangial cells express functional receptors for vasoconstrictor metabolites of arachidonate, such as thromboxane A2. Binding of thromboxane A2 analogs triggers phosphatidylinositol breakdown and a rise of intracellular free Ca2+, followed by complex effects on cell growth. We have evaluated the effects of the thromboxane A2 mimetic, U-46619, on the biosynthesis of human mesangial cell proteins. After 4 to 24 hours of incubation with U-46619, cells were metabolically labeled with tritiated leucine or sulfur 35-methionine and analyzed by one-dimensional and two-dimensional sodium dodecylsulfate polyacrylamide gel electrophoresis and fluorography. U-46619 modestly stimulated total protein synthesis in both quiescent and cycling cells to a maximum of 12% and 23% above control at 1 mumol/L after 24 hours, respectively. The eicosanoid selectively enhanced the labeling of crude membrane and cytosolic proteins of molecular weights of approximately 38 to 53 kd and 125 to 200 kd in the presence or absence of serum, respectively. Cellular tubulin and collagen type IV, but not actin, were markedly stimulated, as determined by immunoblotting of cell associated proteins. On the contrary, U-46619 potently inhibited labeling of soluble proteins that were released into the media, to a maximum of 49% after 24 hours. Inhibition was confirmed by immunoblotting of collagen type IV. Intraglomerular accumulation of thromboxane A2 during chronic inflammation may modify the functional characteristics of the mesangium by regulation of the biosynthesis of structural proteins. PMID- 1613329 TI - Depletion and repletion of Ca2+ in the perfused rat liver. AB - Repletion with Ca2+ often leads to damage of previously Ca(2+)-depleted hearts (the calcium paradox). The behavior of the liver under similar conditions is not well understood. With a perfused rat liver model, we examined liver cell damage and lipid peroxidation during Ca2+ depletion and repletion and used lucigenin enhanced chemiluminescence as a measure of oxygen radicals. During 30 minutes of Ca2+ depletion, release of lactate dehydrogenase and thiobarbituric acid-reactive substance did not change significantly. When Ca2+ depletion was extended to 150 minutes, release of lactic acid dehydrogenase and thiobarbituric acid-reactive substance and tissue oxygen radical levels all increased progressively, accompanied by decrease in oxygen uptake. Ca2+ repletion after 30 minutes of Ca2+ depletion caused small increases in release of lactic acid dehydrogenase and thiobarbituric acid-reactive substance but significantly suppressed the changes described, compared with expression in depleted livers without Ca2+ repletion. There were large releases of sinusoidal glutathione and glutathione disulfide at the onset of Ca2+ depletion, which declined within 15 minutes. On Ca2+ repletion, sinusoidal glutathione level decreased to its baseline but glutathione disulfide level did not change significantly. During long-term Ca2+ depletion, sinusoidal glutathione level was significantly higher than baseline but glutathione disulfide level remained low. These results indicate that long-term Ca2+ depletion causes oxidative stress and liver damage. Ca(2+)-dependent release of sinusoidal glutathione appears to result from causes other than oxidative stress. There is no evidence for the calcium paradox in the liver; in fact, reexposure to Ca2+ protects the liver from the injury caused by Ca2+ depletion. PMID- 1613330 TI - Some antiphospholipid antibodies inhibit phospholipase A2 activity. AB - Certain antiphospholipid antibodies, particularly those associated with arterial thrombosis, reduce vascular prostacyclin production. Studies were conducted to determine whether antibody-mediated inhibition of phospholipase A2 accounts for this effect. In this report we present evidence that purified antiphospholipid antibodies reduce phospholipase A2 activity toward phospholipid substrates, both in vitro and in a defined system. Purified immunoglobulin, obtained from patients at risk for thrombosis who had plasma antiphospholipid antibodies, impaired prostacyclin generation after endothelial stimulation with thrombin or the calcium ionophore A23187. The release of arachidonate in response to A23187 was reduced in endothelial cells pretreated with antibody; the metabolism of exogenous arachidonate to prostacyclin was normal. Thrombin-induced synthesis of platelet-activating factor, which follows phospholipase A2-mediated generation of lysophosphatidylcholine, was also inhibited in parallel with the inhibition of prostacyclin generation. Phospholipase A2 activity was determined in a defined test system with two phospholipases A2. The hydrolysis of fatty acid was less in the presence of patient immunoglobulin than in buffer alone or with normal immunoglobulin. Inhibition by antibody was present at a range of phospholipase concentrations. Antiphospholipid antibodies, purified from patient serum by adsorption to and subsequent elution from immobilized cardiolipin or phosphatidylserine, also inhibited phospholipase A2 activity. The data support our conclusions that purified antiphospholipid antibodies inhibit endothelial phospholipase A2 activity in response to thrombin or ionophore and that phosphatidylcholine in a common metabolic precursor of both prostacyclin and platelet-activating factor. In a defined enzyme assay, inhibition by antiphospholipid antibody of phospholipase A2 activity does not require additional cofactors. PMID- 1613331 TI - The calcium paradox: differences between liver and heart may relate to mitochondrial functions. PMID- 1613332 TI - Platelet-derived growth factor and growth-promoting activity in the serum samples and platelets of patients with non-insulin-dependent diabetes mellitus. AB - Although platelet-derived growth factor (PDGF) is thought to be a major mediator of atherosclerotic disease, the pathophysiology of diabetic vasculopathy, including atherosclerosis, is unclear. By means of an enzyme immunoassay that used a monoclonal antibody against human PDGF-B chain, PDGF-like immunoreactivity was determined in serum, platelet-poor plasma, and platelet lysate of 28 patients with non-insulin-dependent diabetes mellitus and 11 control subjects. Growth promoting activity was also measured by tritiated thymidine incorporation into DNA of cultured human fibroblasts. The PDGF-like immunoreactivity in serum was correlated (r = 0.42; p less than 0.01) with that in platelet lysate prepared from a fixed volume of blood. Furthermore, a correlation (r = 0.70; p less than 0.001) was found between the PDGF-like immunoreactivity and the growth-promoting activity in platelet lysate but not in serum. There was no significant difference between patients with diabetes and control subjects with respect to the PDGF-like immunoreactivity in serum or in platelet lysate (38.2 +/- 2.2 vs 42.8 +/- 3.1 ng/ml or 49.1 +/- 2.4 vs 56.2 +/- 3.4 ng/mg protein; mean +/- SEM). In contrast, the serum growth-promoting activity was lower (p less than 0.05) in patients with diabetes than in control subjects (88.1% +/- 7.1% vs 117.4% +/- 6.9%) and there was a negative correlation (r = -0.39; p less than 0.05) between the serum growth promoting activity and the fasting plasma glucose level. The growth-promoting activity in platelet lysate of patients with diabetes did not differ from that of the control subjects (59.9% +/- 11.6% vs 65.9% +/- 11.2%).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613333 TI - Regulation of major histocompatibility complex class II gene expression on bovine bronchial epithelial cells. AB - Induction and increased expression of major histocompatibility complex (MHC) class II antigens in tissues that do not normally express class II antigens is thought to be important in the pathogenesis of allograft rejection and may also be important in the pathogenesis of obliterative bronchiolitis in lung allografts. We hypothesized that MHC antigen expression on bronchial epithelial cells, particularly MHC class II expression, is regulated by immune mediators in a manner similar to the regulation of antigen expression by lymphoid cells. With an in vitro system of bovine bronchial epithelial cells, we evaluated the effects of both a lymphokine-containing supernatant and recombinant tumor necrosis factor alpha on MHC class II expression. Immunofluorescence and flow cytometry demonstrated markedly increased MHC class II surface antigen expression on the bronchial epithelial cells after exposure to the lymphokine-containing supernatant. Tumor necrosis factor-alpha had no effect on MHC class II surface antigen expression. Immunosuppressant drugs altered the cellular responses to lymphokines in a manner similar to that of lymphoid cells. Dexamethasone suppressed the induction of MHC class II antigens at both the surface antigen and messenger RNA transcript levels. Cyclosporine did not have a consistent effect on the surface expression of class II antigens, but it did inhibit the messenger RNA transcript levels. These suppressive effects have implications for the therapy of airway disorders associated with lung and bone marrow transplantation. PMID- 1613334 TI - Care of the pregnant asthmatic. AB - Treatment of asthma in the pregnant female poses a dilemma for the physician who must select medications that will effectively suppress maternal bronchospasm but that will not jeopardize the fetus. To compound the practitioner's problem, the inability to perform human studies with asthma drugs has led the pharmaceutical companies to formally list precautions against the use of antiasthmatic drugs during pregnancy in the Physician's Desk Reference (PDR), a book which is available to the lay public and is often introduced in medicolegal suits as the primary reference for standard of care. This article provides the clinician with the current recommended treatments that are considered acceptable during pregnancy based on the published evidence involving animal studies and the cumulative human experience that is reported in the English language medical literature. PMID- 1613335 TI - Immediate breast reconstruction at the time of mastectomy for breast cancer. AB - Immediate breast reconstruction avoids or lessens the psychosocial trauma associated with a disfiguring mastectomy. The complications seen in this small patient sample are not in excess of those seen in patients undergoing delayed reconstruction. Fifteen immediate breast reconstructions were performed at the time of mastectomy for cancer. Flap or implant reconstruction alone was determined on an individual basis. No delays in the initiation of adjuvant chemotherapy or hormone therapy were caused by the reconstructions. There were no instances of total flap loss or wound infection. One implant was lost due to exposure. Other complications were similar to those associated with modified radical mastectomy alone. These preliminary results suggest that immediate breast reconstruction at the time of mastectomy may be offered with safety to newly diagnosed breast cancer patients. PMID- 1613336 TI - Interdisciplinary treatment of abused families in Kentucky. AB - The recognition and management of child sexual abuse has gained increased attention by primary care physicians. Examined are the results of a 3-year interdisciplinary clinical treatment program and clinical data which enhance the primary care physician's assessment and management of child sexual abuse. Specific criteria used in diagnosis and strategies for abuse are explored. Psychological factors involved in the adaptation process and long-term impact on the child and family are discussed. PMID- 1613337 TI - Fetal surgery: correction of anatomic and constitutional defects. AB - The advent of improved obstetrical care and innovative advances in fetal diagnostic techniques have mandated multidisciplinary approaches to pregnancies that are complicated by prenatally diagnosed defects. The concept of fetal therapy, previously limited to in utero transfusions for Rh disease and induction of lung maturation, has now been extended to open fetal correction of congenital hydronephrosis, diaphragmatic hernia, and sacrococcygeal teratoma. Additional inquiries are now being made into the possibility of hematopoietic stem cell transplantation in utero as well as prenatal gene therapy. Continued investigation into these therapeutic interventions largely revolves around improving their efficacy and guaranteeing the safety of the mother and her unborn child. PMID- 1613338 TI - Tonsillectomy, adenoidectomy and adenotonsillectomy: are they safe day case procedures? AB - A review of 3,488 tonsil and adenoid procedures performed between March 1987 and April 1990 is presented. A reactionary haemorrhage rate of 0.49 per cent was found. No deaths were recorded. All cases of reactionary haemorrhage occurred within the first eight hours post-operatively. Based on this study, out-patient tonsil and adenoid surgery should be followed by at least an eight hour postoperative observation period before discharge. If day case adenoid and tonsil surgery is adopted, close medical audit would be necessary to detect and then prevent any possible increase in morbidity or mortality. PMID- 1613339 TI - The clinical application of oto-acoustic emissions in paediatric audiological assessment. AB - The value of otoacoustic emissions as an objective screening test for normal peripheral auditory function in infants is currently the subject of extensive and promising research. Additionally the measurement of cochlear emissions is potentially useful when children cannot be tested reliably by traditional subjective methods but confirmation of normal hearing is diagnostically important. Three groups of children are described who present such audiological dilemmas: children with non-organic hearing loss, children with severe learning difficulties and more rarely children with an abnormal auditory brainstem response who also have damage to the central nervous system. In all three groups otoacoustic emission testing was found to be diagnostically useful in determining normal peripheral auditory function thereby resolving some of the dilemmas facing paediatric audiology and ENT clinics. PMID- 1613340 TI - Paediatric otoscopy--clinical and histological correlation. AB - Otoscopy is a subjective clinical method. Its subjectively has led physicians to verify its accuracy through correlations with findings of otomicroscopy, pneumatic otoscopy, tympanometry, and myringotomy. In the very young population, however, the interpretation of otoscopic findings become more difficult. To improve the interpretation of normal otoscopy in young children, an otoscopic histological correlation was attempted in children up to nine years of age. Twenty-one temporal bones from 15 children aged from two days to nine years who had no evidence of otological disease or congenital anomalies were examined under light microscopy; the thickness of the pars flaccida, posterior superior quadrant, and umbo were measured. Twenty-five eardrums of 15 healthy children without past or present history of otological disease were examined using otoscopy; a photograph of each eardrum was obtained. Our study demonstrates that structural changes in the tympanic membrane during these years of childhood have a good correlation with otoscopic findings. Understanding normal histological changes in the paediatric eardrum may improve our interpretation of otoscopic findings. PMID- 1613341 TI - Conservative treatment in the management of inflammatory aural polyp. AB - This prospective study assesses the role of intensive outpatient based conservative treatment in the management of aural polyp. All cases of aural polyp that presented to the department during 1990 were included. Patients with obvious cholesteatoma or in whom inner ear or intracranial pathology was suspected were excluded as were children and patients who had undergone previous ear surgery. We found that treatment with topical steroid/antibiotic decreases disease activity and renders subsequent surgery less extensive. PMID- 1613342 TI - Otological manifestations of thalassaemia intermedia: evidence of temporal bone involvement and report of a unique cholesteatoma-like lesion. AB - Thalassaemia intermedia should be considered in any chronically anaemic patient presenting from the Middle East with hearing impairment. We report here three Saudi siblings with thalassaemia intermedia and features of severe bone marrow expansion, particularly invading the temporal bone. They were seen first for their otological problems before they had access to proper haematological evaluation. One member was admitted for surgical exploration of a cholesteatoma, which was then found to be marrow expansion of the temporal bone. Screening of the family revealed two more anaemic siblings with thalassaemia intermedia. Audiological examination of all the family members showed that only the two affected members had a high frequency sensori-neural hearing loss. Bone marrow expansion into the temporal bone is a rare feature of thalassaemia intermedia. Cholesteatoma-like lesion has not been previously described. It has to be considered in all cases of symptomatic thalassaemia intermedia manifesting with cavitation and lytic lesions in the mastoid system. The likelihood that sensorineural hearing loss may complicate the thalassaemias is raised and the possible mechanism for such involvement discussed. The proper management for different otological manifestations of the thalassaemias is suggested. These cases would suggest a more extensive involvement of the temporal bone in the thalassaemias than has been previously recognized. Further large scale studies are required to illuminate the subject. PMID- 1613343 TI - Eustachian tube function in sudden hearing loss and in healthy subjects. AB - The relationship between sudden hearing loss and an ipsilateral patulous tube was tested in our Eustachian tube laboratory. Fifty patients suffering from sudden hearing loss were examined by the pressure chamber impedance method, giving objective data on Eustachian tube function. Results were compared to those obtained from 56 healthy volunteers in a preceding investigation. Our investigation did not show any associations between patulous tube syndrome and sudden hearing loss, as had been claimed by several authors previously. There was even indication of a decreased patency of Eustachian tube in our patients in active and passive tubal tests. We could demonstrate a high reproducibility of values obtained by our method, indicating that results are representative in healthy persons as well as in patients. In a case report the importance of objective diagnostic methods in differential diagnostics of Eustachian tube pathology is emphasized. PMID- 1613344 TI - The Pope Wick as a myringoplasty ear canal dressing. PMID- 1613345 TI - What is the effect of translabyrinthine acoustic schwannoma removal upon tinnitus? AB - A series of 129 patients who had undergone translabyrinthine removal of a unilateral acoustic schwannoma completed a postal questionnaire about pre- and post-operative tinnitus. A simple grading system was devised from which it was possible to determine the likely outcome of translabyrinthine acoustic schwannoma surgery upon tinnitus. The results have been analyzed in detail, and as a result it is possible to advise a patient undergoing this form of surgery that if they have no tinnitus pre-operatively they are unlikely to develop it, and if they do it will not be severe enough to significantly affect their quality of life. If they have mild or moderate tinnitus it is most likely to stay the same, or become less intense. If a patient has severe tinnitus it is very likely to improve and not affect their future quality of life. PMID- 1613346 TI - Squamous cell carcinoma of the nasal vestibule. AB - We reviewed 30 patients with squamous cell carcinoma of the nasal vestibule to present our experience of their management and to evaluate the prognostic factors that may influence their outcome. For T1 lesions radiotherapy remains the treatment of choice, because of the superior cosmetic result. Fifteen (68 per cent) out of 22 patients with T2 lesions were treated with primary radiotherapy. Surgery however, was eventually required in 16 (72 per cent) out of 22 patients, either as a primary treatment (seven patients) or as salvage surgery (nine patients). For the larger T3 lesions the treatment of choice is surgery followed by post-operative radiotherapy where appropriate. Regional nodal metastases at the time of presentation were a significant indicator of local and regional recurrence and of prognosis. The cause specific five-year survival for patients with an uninvolved neck (22 patients) was 100 per cent compared with 38 per cent for patients with nodal metastases at presentation (eight patients). Elective treatment for uninvolved regional nodes is not considered necessary. PMID- 1613347 TI - Tumours of the nose and maxillary sinus. Ten year survey from Kenya. AB - Between 1976-1985, 127 cases of malignant tumours of the nose and maxillary sinus were seen at the Department of Human Pathology, Kenyatta National Hospital, Nairobi, Kenya. Cancer of the nose and maxillary sinus was a common diagnosis accounting for 0.8 per cent of all malignancies. Despite this, the incidence was low probably because the rural Kenyans have difficulty in gaining access to the oncology facilities in Nairobi. Incidence rates standardized to world population per 100,000 persons-years were 0.16 for males and 0.12 for females. Clinical information showed that malignancy should be expected in patients with swelling of the cheek and involvement of the orbit. Compared with Denmark the proportion of undifferentiated carcinomas was significantly higher in Kenya. The well known fact that anaplastic carcinoma of the postnasal space is causally associated with the Epstein Barr virus makes it tempting to suggest that anaplastic carcinoma of the nose and maxillary sinus may also be of viral aetiology. PMID- 1613348 TI - Adenoids: comparison of radiological assessment methods with clinical and endoscopic findings. AB - Methods of evaluating adenoidal size pre-operatively are controversial. Symptoms and clinical evaluation have been both advocated and condemned. Depending on the methodology, measurement of the radiological adenoidal shadow has been difficult to correlate with the clinical patency of the nasopharyngeal airway and to the actual size of the removed adenoid. Four different methods were used to measure the adenoidal size on 74 radiographs. The methods were evaluated against the degree to which the adenoids obstructed the nasopharynx on flexible endoscopy of the postnasal space. Obstructive symptomatology was also evaluated against the degree of obstruction. The radiological method that best correlated to the endoscopic findings was that of Cohen and Konak (1985). However, obstructive symptomatology had the overall highest correlation to endoscopic findings. PMID- 1613349 TI - Vertical partial laryngectomy: our results after treating 81 cases of T2 and T3 laryngeal carcinomas. AB - From 1976 to 1989, 81 patients with T2 and T3 laryngeal carcinomas were treated with vertical patrial laryngectomy at the University ENT Department of Thessaloniki, Greece. All patients were male with a median age of 56 years (33-71 years). Four patients had N1 lymph nodes. Ten patients received post-operative radiotherapy. Seventeen patients developed local recurrences or distant metastases. Mean follow-up was more than seven years. Absolute three-year survival was 94.6 per cent for 74 patients and absolute five-year survival was 89.6 per cent for 58 patients. Actuarial five-year survival of the whole group of 81 patients was 91 per cent calculated with the Kaplan-Meier method. Recurrence rate and survival of stage II and III patients are also discussed and compared using the log-rank test. We conclude that vertical partial laryngectomy is a very successful treatment selection for T2 glottic and false vocal cord carcinomas and for some selected T3 glottic lesions. PMID- 1613350 TI - Use of a portable manometer as a screening procedure in voice rehabilitation. AB - Abnormal tone in the pharyngo-oesophageal (PO) segment may lead to failure in developing oesophageal speech. Videofluoroscopy may give a qualitative assessment of the PO segment but is expensive, time consuming and lacks quantification. A custom built PO segment manometer was therefore assessed as a means of predicting eventual oesophageal speech outcome. Two groups of patients were studied. In group 1 (18 patients) the PO segment pressures were compared to their videofluoroscopy findings. Videofluoroscopy categorized the patients into four groups. The PO pressures corresponded to this grouping, pressures above 20 mmHg being associated with voice failure. In group 2 (12 patients) the PO pressures in the early post-operative period were compared to their eventual speech outcome. In all cases the pressures predicted the eventual speech outcome. The pressure manometer is a simple, cheap and portable device which is a reliable screening test to predict the potential for oesophageal speech. PMID- 1613351 TI - Autologous fibrin glue in the repair of dural defects in craniofacial resections. AB - Cerebrospinal fluid leakage is a serious and well recognized complication of craniofacial resection for ethmoidal tumours in which the integrity of the dura has been breached. Autologous fibrin glue is a safe, inexpensive and simple method of improving the seal of dural repair and hence minizing CSF leakage. The principles and method of autologous fibrin glue preparation are described. The technique has proven satisfactory in 20 consecutive craniofacial resections with dural defects and is recommended as an adjunct to current techniques of dural repair. PMID- 1613352 TI - Simple method of insertion of Xomed one piece septal button. AB - Silicone septal buttons have been available to obturate septal perforations since the 1970s. Various methods of insertion have been suggested but the procedure is not always easy. We have devised an alternative method which has proved quick and simple to perform. PMID- 1613353 TI - Temporal bone histopathological findings in campomelic dysplasia. AB - Both temporal bones of a newborn (35 gestational weeks old) with campomelic syndrome were studied histopathologically. This is to our knowledge the second temporal bone report (third case) of this syndrome. The findings included: abnormal cartilagenous and osseous tissues and abnormality in the globuli interossei in the otic capsule; deformities of the vestibule and semicircular canals, probably due to compression by the abnormal cartilaginous tissue; hypoplastic cochlea and semicircular canals; aberrant course of the facial nerve; wide dehiscence of the facial canal in the tympanic portion; slight hypoplasia of the malleus and anomalies in the incus and stapes; and large epitympanic space. These findings closely resembled those of the first report, and suggest that: 1) campomelic dysplasia is a definite disease entity with consistent pathogenesis, and 2) similar otologic manifestations may be expected in the majority of patients with this syndrome. PMID- 1613354 TI - Nasal teeth. AB - Ectopic and supernumerary teeth occur in a wide variety of sites. Those that have been reported include the mandibular condyle, coronoid process, orbit, palate, nasal cavity and the maxillary antrum. Eruption of teeth into these sites is rare, and easily overlooked. We present two cases in which eruption of teeth into the nose and paranasal sinuses was associated with significant morbidity and show how this was relieved by appropriate surgery. PMID- 1613355 TI - Angiosarcoma of the nasal cavity. AB - Angiosarcoma of the nasal cavity is extremely rare. We present a case of angiosarcoma of the nasal cavity in an eight-year-old boy. He was treated with medial maxillectomy via lateral rhinotomy. The histological diagnosis was confirmed by immunohistological stain with Factor VIII-like antigen. Magnetic resonance imaging (MRI) was useful in determining the extent of the tumour. PMID- 1613356 TI - Basaloid-squamous carcinoma of the nasal cavity. AB - Basaloid-squamous carcinoma is a recently characterized, aggressive tumour occurring in the hypopharynx, larynx and base of tongue. We report a unique case involving the nasal cavity of a patient with a history of radiation therapy for nasopharyngeal carcinoma, raising the possibility that basaloid-squamous carcinoma can be radiation-associated. PMID- 1613357 TI - The dangers of minor blunt laryngeal trauma. AB - Since the introduction of seat belts, laryngotracheal trauma has become a rare injury, comprising less than one per cent of blunt trauma cases seen at major trauma centres. However, a wide range of damage to the soft tissue and cartilaginous framework of the larynx may result from such injuries but signs of injury are easily overlooked leading to potentially serious consequences for the patient. We report a case of isolated blunt laryngeal trauma from a relatively minor injury which illustrates some of the problems resulting in these cases and review the treatment of blunt laryngeal trauma. PMID- 1613359 TI - Is 'lateral aberrant thyroid' always metastatic tumour? AB - It is now a widely held belief that so-called 'lateral aberrant thyroid' tissue actually represents a metastasis from a malignant tumour of the thyroid gland. A case is presented which suggests that this is not always true, and an extensive review of the relevant literature is discussed. PMID- 1613358 TI - Necrobacillosis--an unusual cause of cervical abscess. AB - Necrobacillosis is a rare infection which may be fatal if inadequately treated. We present a case demonstrating the classical clinical picture upon which correct diagnosis depends. The need for a high index of suspicion is highlighted and appropriate management is discussed. PMID- 1613360 TI - Shoulder function after radical neck dissection. PMID- 1613361 TI - Mastoidectomy packs: Xeroform or BIPP? PMID- 1613362 TI - Detection of recurrent cholesteatoma by computerized tomography after 'closed cavity' mastoid surgery. AB - Pre-operative Computerized Tomography was performed prior to second look operations in 10 cases to check for cholesteatoma after combined approach tympanoplasty. Three independent opinions were obtained on the CT scans and compared with the operative findings. This small series failed to demonstrate reliable pre-operative radiological detection of cholesteatoma. There was disappointing inter-observer agreement in interpretation of the CT scans. PMID- 1613363 TI - Nasal septal haematoma in Nigeria. AB - A prospective study of 46 consecutive patients with nasal septal haematoma admitted at the General Hospital, Owerri, Nigeria over a five year period is presented. The disease was commoner in males than females. The majority of the cases (65.6 per cent) were of unknown cause and were therefore grouped as spontaneous haematoma while 30.4 per cent were due to trauma. Trauma was more common in patients below the age of 15 years while spontaneous haematoma was common in patients above that age. All the patients with septal haematoma represented 0.2 per cent of total attendances to the ENT clinic over the period. Most of the patients presented with severe and threatening symptoms necessitating intense aggressive management. All the patients were managed by surgical incision and drainage, four had marked nasal abnormalities. Three patients died from a brain abscess as a complication of infected haematoma. PMID- 1613364 TI - Prognosis in mouth cancer: host factors. AB - A personal series of 842 patients with a tumour of the oral cavity is presented. Five hundred and twelve of these patients had a histologically proven squamous cell carcinoma, and were previously untreated. Increasing age was associated with worsening performance status. Women were older at presentation than men, and tumours of the upper part of the mouth were more common in the elderly, but there was no relation between age and histological grade or stage grouping. Sex had no correlation with performance status or histological grade. However, men were more likely to have an advanced tumour, and tumours of the floor of the mouth and alveolus were much commoner in men. There was no correlation between performance status and site or histological grade, but patients in poor general condition were more likely to have stage III-IV tumours. Multivariate analysis showed that sex had no impact whatever on survival, but survival fell with increasing age and worsening performance status. The effect of age and performance status disappeared when the survival of treated patients was adjusted for deaths due to other causes. PMID- 1613365 TI - The role of electron microscopy in the diagnosis of tumours of the head and neck. AB - A four-year study was undertaken to determine the value of electron microscopy in the diagnosis of head and neck tumours. During this period 80 samples were submitted for examination, of which 69 contained assessable tumour. Electron microscopy made a major contribution to the diagnosis in 25 cases (36 per cent). Areas in which ultrastructural examination was of diagnostic significance included the precise categorization of apparently undifferentiated carcinoma and the identification of melanomas. Little diagnostic benefit was gained from electron microscopic examination of thyroid, lymphoid or salivary gland neoplasms. The value of electron microscopy in relation to immunohistochemistry is discussed. PMID- 1613366 TI - Antimicrobial prophylaxis for major head and neck cancer surgery with piperacillin and ornidazole. AB - A prospective study in 53 eligible patients, undergoing major head and neck cancer surgery was carried out to assess the combination of an ureido penicillin, piperacillin with a nitro imidazole agent, ornidazole, in order to prevent post operative general and wound infections. Both antibiotics were administered for five days. Each patient had piperacillin 4 gm every eight hours and ornidazole 1 gm every 24 hours. The overall rate of infections was 13.2 per cent (n = 7), with 3.8 per cent (n = 2) wound infections and 11.3 per cent (n = 6) general infections (one patient presented both complications). There was no wound infection in the total surgery group (n = 12). General infections who only consisted of pneumonias were respectively 12.2 per cent (n = 5) in the group with partial procedures (n = 41) and 8.3 per cent (n = 1) in the total surgery group. This antibioprophylaxis can be recommended in major oncological neck surgery, specially in the case of partial procedures. PMID- 1613367 TI - Combined therapy in advanced head and neck cancers. AB - The results of single modality treatment using surgery or radiotherapy alone in advanced head and neck cancers are known to be unsatisfactory. The present study analyses 252 cases with stage III and IV resectable cancers of the head and neck region selected to be treated by a combined regime of pre- or post-operative radiation and radical surgery. Only 193 patients completed the treatment protocol. There were 58 cases (33.5 per cent) who failed either at primary or regional sites or both. Nine cases (five per cent) developed distant metastasis. Absolute and determinate four year disease-free survival was 55 per cent and 61 per cent respectively. Early lesions (stage I and II) have been excluded from the study. The study indicates that a reduction in primary and regional failures correlates well with a combined therapy, though prolonged treatment may affect patients' compliance to some extent. PMID- 1613368 TI - Surgical approach to submucosal lesions of the supraglottic larynx: the supero lateral thyrotomy. AB - The surgical approach to the hypopharynx by lateral pharyngotomy as described by Trotter has found widespread use in management of supraglottic carcinoma. A similar but more conservative approach may be employed for removal of cysts and benign or well-encapsulated neoplasms of the epiglottis and supraglottic space. We call this approach a supero-lateral thyrotomy, to differentiate it from the classic lateral pharyngotomy. Surgery consists of subperichondrial resection of the superior half of the ipsilateral thyroid cartilage with preservation of internal lining and superior laryngeal nerve. The lesion may then be enucleated or resected, and the defect, if any exists, closed with overlying mucosa and the flap of preserved perichondrium. The technique has been employed in cases of paraganglioma, haemangiopericytoma and saccular cysts. PMID- 1613369 TI - Informed consent: the assessment of two structured interview approaches compared to the current approach. AB - We prospectively studied 190 patients undergoing tonsillectomy or nasal surgery to assess the value of two structured interview techniques. There were four groups: Group A did not have a consent interview during the study period. Group B had an informal interview. Group C had a structured interview and Group D had a structured interview and were given an information sheet. Anxiety assessments were made and patients' recall of the operation name, details of the operation and its complications was assessed. Patients had higher than normal anxiety levels when admitted, but several hours after the interview anxiety was normal for Groups B, C and D. Group A maintained a higher anxiety level. Only 37 per cent correctly recalled the operation name, where as 87 per cent of all groups recalled the explanation of the operation. However, Groups C and D recalled a higher mean number of complications per patient. A structured interview when obtaining informed consent increases the number of complications recalled without increasing pre-operative anxiety. PMID- 1613370 TI - An ad hoc tympanocentesis apparatus. AB - Myringotomy is one of the commonest procedures carried out by ENT surgeons. Analysis of middle ear aspirate is sometimes helpful in the management of ear disease. A simple method of constructing an apparatus for collection of middle ear aspirate is described. PMID- 1613371 TI - Ventilation tube insertion using topical anaesthesia in children. AB - Topical anaesthesia using EMLA cream is an established anaesthetic technique for ventilation tube insertion in adults. We report its use in 103 children (age range 3-12 years). Failure occurred in seven patients (6.8 per cent); complications occurred in two patients and were of a minor nature. This technique appears well tolerated provided the operator avoids the use of suction and allows a cream penetration time of greater than two hours. The use of a 'T' myringotomy is also recommended, to reduce tension on the drum at tube insertion. PMID- 1613372 TI - Von Hippel-Lindau disease associated with an invasive choroid plexus tumour presenting as a middle ear mass. AB - Cerebellar haemangioblastomata and angiomata of the retina are the most common vascular tumours seen in von Hippel-Lindau disease. A definite association between this condition and choroid plexus tumour has not been described previously and its presentation as a middle ear mass is unique. PMID- 1613373 TI - Vascular cross-compression of the VIIth and VIIIth cranial nerves. AB - A 53-year-old male patient had been suffering from severe aural symptoms (pulsatile right-sided tinnitus and paroxysmal dizziness attacks with nausea) and right hemifacial spasm. Treatment had involved stellate ganglion block with lignocaine and the injection of intravenous sodium bicarbonate solution for attacks of Meniere's syndrome and facial nerve block with lidocaine for hemi facial spasm. Despite these treatments, the dizzy attacks became more frequent, developing into the clustering state. Air CT cisternography and vertebral angiography demonstrated an enlarged and curved vertebral artery. Vascular cross compression of the VIIth and VIIIth cranial nerves was therefore suspected. Microvascular decompression was performed. After operation, the pulsatile tinnitus, dizziness and hemifacial spasm disappeared. From the present case and a review of the literature, we conclude that vascular cross-compression of the VIIIth cranial nerve should be an indication for microvascular decompression only when symptoms of vascular cross-compression of the VIIth cranial nerve are also seen. PMID- 1613374 TI - Rhinosporidiosis in Europe. AB - Rhinosporidiosis is an inflammatory disease of the nasal mucosa caused by Rhinosporidium seeberi. The disease is endemic in India but very rare in Europe or other continents. The literature concerning aetiology, clinical appearance, morphology and treatment is reviewed. All reported European cases are summarized. PMID- 1613375 TI - A difficult intubation--fatal respiratory arrest secondary to an oral epulis. AB - We report an unusual case of cardio-respiratory arrest and eventual death secondary to a benign tumour of the oral cavity obstructing the oropharynx. We review the literature of similar occurrences causing difficulty with respiration and intubation, and highlight the importance of early diagnosis and treatment. PMID- 1613376 TI - Giant parotid calculus--an unusual presentation. AB - We describe a case of a giant sialolith of Stensen's duct in a 48-year-old woman. The patient was investigated and treated with a mistaken diagnosis of chronic inflammation until the clue to the diagnosis was provided by plain radiography. This is an unusual presentation of a salivary calculus and to our knowledge such a huge parotid calculus has not been reported so far in the literature. PMID- 1613377 TI - Neonatal vallecular cysts and failure to thrive. AB - The case of a vallecular cyst in a neonate is described. The presentation was with failure to thrive. This previously unreported mode of presentation is discussed, and aspects of the management are emphasized. In particular, the value of flexible nasopharyngoscopy in assessing the neonatal laryngopharynx is highlighted. PMID- 1613378 TI - Laryngeal chondrosarcoma--an unusual presentation. AB - Laryngeal chondrosarcoma is an uncommon tumour, approximately 200 cases having been reported in the world literature. We report a case which was noted by chance in a patient undergoing general anaesthesia for an unrelated procedure. PMID- 1613379 TI - Pulmonary tuberculosis presenting as suspected foreign body aspiration. AB - Tuberculosis is a disease of protean manifestations, and despite a falling incidence is still prevalent in our society. We present a case of a child whose history and preoperative chest radiograph suggested the presence of a foreign body, but subsequent examination of the material removed at endoscopy revealed a diagnosis of tuberculosis. We suggest that all friable material removed from the lower respiratory tract be submitted for microscopy, culture and histopathology with this diagnosis in mind. PMID- 1613380 TI - Infection of the neck spaces: a present day complication. AB - Although advances in antibiotic therapy have made adult neck space infections an uncommon event, it is essential to bear them in mind when treating oro-dental and oro-pharyngeal sepsis, as they can often progress with life threatening sequelae. Three cases of neck space infection as a consequence of dental infection, pharyngitis and peritonsillar abscess are presented. The management of a potentially compromised airway is of paramount importance in the immediate treatment of neck space sepsis. PMID- 1613381 TI - Fibromatosis of the head and neck. AB - The purpose of this paper is to focus attention on this rare disorder. Two cases are reported: one involving the neck and the other the nose and paranasal sinuses. The treatment of choice is wide surgical excision wherever possible. PMID- 1613382 TI - Cervical meningocoele presenting as a neck mass in a patient with neurofibromatosis 1. AB - We report a case of an anterolateral cervical meningocoele presenting as a neck mass in a patient with neurofibromatosis 1. This lesion was diagnosed with the aid of computerized tomography and radionuclide scanning. The presentation, behaviour and treatment options of this uncommon lesion are briefly discussed. PMID- 1613383 TI - Cholesterol cyst and cholesterol granuloma of the petrous bone. PMID- 1613384 TI - Rhinosporidiosis. AB - Rhinosporidiosis is the disease resulting from infection by Rhinosporidium seeberi, an organism endemic in the Indian sub-continent, but rarely seen in the United Kingdom. We describe the clinio-pathological features of a case presenting in a 14-year-old female. PMID- 1613385 TI - Retro-pharyngeal liposarcoma. AB - We present a case of extensive recurrence of a retro-pharyngeal liposarcoma following surgical removal 18 years previously. The surgery and pathology are discussed, and management strategies of head and neck liposarcomas are reviewed. PMID- 1613386 TI - Laryngeal mask airway in ENT surgery. PMID- 1613387 TI - Emergency cricothyroidotomy. PMID- 1613388 TI - Atrophic rhinitis. PMID- 1613389 TI - Subcellular localization of heparanase in human neutrophils. AB - The subcellular localization of a heparan sulfate degrading endoglycosidase, heparanase, was studied in human neutrophils. Unstimulated cells were disrupted by nitrogen cavitation and fractionated on a Percoll density gradient into three components, separating the plasma membranes, specific granules, and azurophilic granules. Heparanase activity was measured by gel filtration analysis of 35S labeled degradation fragments released from subendothelial extracellular matrix (ECM) or produced during incubation with soluble, ECM-derived, heparan sulfate proteoglycans. Heparanase activity was found mainly in fractions containing the specific granules; this activity was inhibited by heparin. Freezing and thawing was not needed for recovery of the enzyme from the subcellular fraction, confirming previous data about its ready release. The mechanism of the ready release of heparanase from the specific granules requires further investigation. PMID- 1613390 TI - Culture of ovine bone marrow-derived macrophages and evidence for serum factors distinct from M-CSF contributing to their propagation in vitro. AB - An in vitro system allowing the culture of ovine bone marrow-derived macrophages (BMMs) is described. Bone marrow (BM) cells from the sternum of 4- to 9-month-old sheep were cultured in liquid suspension in hydrophobic bags with medium containing 20% autologous serum and 20% fetal calf serum (FCS). Cells with macrophage characteristics were positively selected and increased four- to five fold between day (d) 0 and d18. Granulocytes and cells of lymphoid appearance including progenitor cells were negatively selected and were diminished 50-fold during this 18-d culture. The addition of macrophage colony-stimulating factor (M CSF)-containing supernatants to liquid cultures did not significantly improve the yield of BMM in 18-d cultures. In contrast, cell survival at d6 and macrophage cell yield at d18 depended on the concentration and source of serum in the culture medium. FCS and 1:1 mixtures of FCS and autologous serum were superior to autologous serum alone. Analysis of growth requirements of ovine BMMs suggested that they are under more complex growth control than their murine counterparts. In an [3H]thymidine incorporation assay with BM cells collected at different times of culture, d3 or d4 BM cells responded to human recombinant M-CSF, human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF), bovine GM CSF, murine M-CSF or murine M-CSF-containing supernatants, and bovine interleukin 1 beta (IL-1 beta) in decreasing order of magnitude. Likewise, pure murine BMM populations harvested at d6 responded to homologous GM-CSF, IL-3, and human or murine M-CSF. FCS did not stimulate the proliferation of murine BMMs (d6) and of ovine BM cells (d3 or d4). In contrast, ovine BM cells harvested at d12 responded to FCS by proliferation in a dose-dependent manner but failed to proliferate in the presence of human or murine M-CSF or M-CSF-containing supernatants of mouse and sheep fibroblasts containing mouse macrophage growth-promoting activity. Likewise, various cytokine-containing supernatants and recombinant cytokines (murine IL-3, murine and human GM-CSF, murine and bovine IL-1 beta) did not promote proliferation of ovine d12 BM cells to an extent greater than that achieved with 15% FCS alone. Thus, ovine BMM proliferation is under the control of at least two factors acting in sequence, M-CSF and an unidentified factor contained in FCS. The ovine BMM culture system may provide a model for the analysis of myelomonocytopoiesis in vitro. PMID- 1613391 TI - Isolation and characterization of four CSF-1-dependent placental macrophage cell lines. AB - By selection and cloning in the presence of colony-stimulating factor 1 (CSF-1), we have obtained from separate explants of individual 12- or 13-day mouse placentas four clonal cell lines dependent on CSF-1 for survival and growth in culture. All four cell lines show characteristics consistent with their derivation from placental macrophages. We describe the effects of CSF-1 on growth, morphology, and CSF-1 receptor phosphorylation. One cell line, JPL2A, which shows relatively complete growth arrest in the absence of CSF-1, was characterized in detail with respect to the effects of CSF-1 on DNA synthesis and protein turnover and its response to the duration of CSF-1 stimulation. In contrast to previous studies, our results suggest that extended stimulation leads to continuous recruitment of cells competent to reenter the cell cycle. These findings are discussed in terms of growth factor effects on the cell cycle and the usefulness of these cell lines for further study of growth factor signal transduction in macrophages. PMID- 1613392 TI - Ultrastructural identification of human mast cells resembling skin mast cells stimulated to develop in long-term human cord blood mononuclear cells cultured with 3T3 murine skin fibroblasts. AB - Human mast cells developed in vitro when cord blood mononuclear cells were cocultured for 3 months with 3T3 embryonic mouse skin fibroblasts. The metachromatic cells that arose in these cultures contained histamine, a functional Fc epsilon receptor and granule proteases (tryptase, chymase), and they were definitively identified by the ultrastructural demonstration of crystal granules. We present a detailed ultrastructural analysis of this newly available system for the reliable development of human mast cells in vitro and provide criteria for definitive identification of the mast cell and basophil lineages in humans. PMID- 1613393 TI - Defective lipopolysaccharide-induced production of both interleukin 1 alpha and interleukin 1 beta by A/J mouse macrophages is posttranscriptionally regulated. AB - Interleukin 1 (IL-1) production by A/J (A) and C57BL/6J (B6) mouse peritoneal macrophages stimulated with lipopolysaccharide (LPS) was determined. Strain A macrophages produced low levels of soluble IL-1 bioactivity compared with B6 macrophages. This defect was not reversed by indomethacin, interferon-gamma, phorbol myristate acetate, or calcium ionophore A23187. In contrast, cytosolic IL 1 bioactivity was similar in LPS-stimulated A and B6 macrophages. Western blotting revealed that A macrophage supernatants contained lower levels of both 17-kd IL-1 alpha and 17-kd IL-1 beta but similar levels of tumor necrosis factor alpha compared with B6 macrophages. Cytosolic levels of 31-kd pro-IL-1 alpha and also 31-kd pro-IL-1 beta were similar in A and B6 macrophages. Oligonucleotide probing indicated that A and B6 macrophages contained similar levels of IL-1 alpha and also IL-1 beta mRNA. These findings indicate that LPS-stimulated A macrophage culture supernatants contain low levels of both IL-1 alpha and IL-1 beta compared with B6 macrophages and that these defects in IL-1 production are posttranscriptionally regulated. PMID- 1613394 TI - Tumor necrosis factor alpha and interleukin 1 alpha enhance lipopolysaccharide mediated bovine endothelial cell injury. AB - Alveolar macrophages (AMs) are important in the host response to aerogenous pulmonary bacterial infections, such as Pasteurella haemolytica-induced pneumonia in cattle. Previous work has shown that AMs enhance P. haemolytica-mediated pulmonary endothelial cell (EC) damage in vitro. The purpose of this study was to determine the mechanism of AM-enhanced EC damage using an in vitro AM-EC coculture system consisting of AMs cultured on culture plate insert membranes and ECs in the underlying chamber. The addition of lipopolysaccharide (LPS) to the culture plate insert chamber resulted in EC damage indicated by 51Cr release, which was enhanced in the presence of AMs. To determine the role of AM-secreted cytokines, recombinant human interleukin 1 alpha (IL-1) or tumor necrosis factor alpha (TNF) was added to ECs simultaneously with varying concentrations of LPS. Although TNF and IL-1 alone had only marginal toxic effects on ECs, the simultaneous treatment of TNF or IL-1 with LPS greatly increased the LPS cytotoxic effect on ECs. In addition, IL-1 receptor antagonist eliminated the IL 1 enhancement of LPS-mediated EC toxicity. These results suggest that macrophage secreted cytokines synergistically enhance LPS-mediated pulmonary EC damage. PMID- 1613395 TI - Inhibition of neutrophil chemotaxis and activation following decentralization of the superior cervical ganglia. AB - Recent studies have shown that bilateral decentralization (sympathectomy) of the superior cervical ganglia (SCG) of rats sensitized to the parasite Nippostrongylus brasiliensis attenuated the development of pulmonary inflammation following allergen challenge. Sympathectomy inhibited total leukocyte infiltration into lung lavage fluids, particularly neutrophil infiltration. To define the effects of decentralization of the SCG on neutrophil responses, peripheral blood neutrophils of rats were isolated and tested in in vitro chemotaxis and phagocytosis assays. Neutrophils from rats that were sympathectomized 7 days previously displayed a marked reduction in chemotaxis to N-formyl-methionyl-leucyl-phenylalanine and leukotriene B4 compared to neutrophils from sham-operated or unoperated groups. Although the degree of chemotaxis was greater in blood neutrophils from parasite-infected rats than from uninfected rats, sympathectomy markedly reduced the chemotactic responses of both groups. In addition, neutrophils of sympathectomized rats were unresponsive to lipopolysaccharide-induced metabolic activation as assessed by in vitro phagocytosis and oxidative reduction of nitroblue tetrazolium. Thus, decentralization of the SCG of rats affects the chemotactic responses and functions of neutrophils. Understanding the role of the sympathetic nervous system in modulating the behavior of neutrophils will shed light on the interactions between the nervous and immune systems. PMID- 1613396 TI - Differentiation-dependent modulation of TNF production by PAF in human HL-60 myeloid leukemia cells. AB - Platelet-activating factor (PAF) can augment tumor necrosis factor (TNF) production by human monocytes in a bimodal manner, with two peaks of activation at picomolar and micromolar concentrations. These peaks are partially associated with monocyte subsets presenting different characteristics in terms of size, density, phenotypic markers, and [Ca2+]i mobilization responses. In the present study, we used the human promyelocytic leukemia cell line HL-60, at various times during differentiation with 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] toward the monocyte lineage, in order to study the relation of cell differentiation to responsiveness to PAF in terms of cytokine production. TNF production was induced by pretreatment with interferon gamma for 24 h and treatment with muramyl dipeptide. Although detectable TNF was produced by 4 day-differentiated cells, no effect was seen with PAF (10(-16)-10(-6) M) at this or earlier stages. In contrast, 5 day-differentiated cells had a comparable baseline production of TNF but responded with a 2.5-fold increase to PAF with a single peak, maximal at 10( 8) M. Moreover, 6 day- or 7 day-differentiated HL-60 cells showed a further increase in TNF production in response to PAF, and the response was bimodal, similar to that of the less dense subset of monocytes, with peaks at 10(-14) and 10(-7) M PAF. In parallel, undifferentiated HL-60 failed to respond to PAF in terms of [Ca2+]i mobilization. The earliest responsiveness to PAF (10(-7) M) was observed by 4 days of treatment with 1,25(OH)2D3, and by day 7 the response to PAF became bimodal (10(-14) and 10(-7) M). These results indicate that myeloid cells acquire, during maturation toward the monocyte lineage, a progressive responsiveness to PAF in terms of [Ca2+]i mobilization and enhanced cytokine production, and they suggest that the heterogeneity in responses to PAF observed in normal monocytes may be related to their stage of differentiation or maturation. PMID- 1613397 TI - Chondroitin sulfate proteoglycan and heparan sulfate proteoglycan production by cultured pigeon peritoneal macrophages. AB - Proteoglycan production was examined in cultures of thioglycollate-elicited peritoneal macrophages obtained from White Carneau and Show Racer pigeons. Following a 24-h incubation in the presence of [35S]sulfate and [3H]serine, total production and distribution of 35S-labeled proteoglycan into media (60-65%), pericellular (21-27%), and intracellular (13-14%) compartments was similar in White Carneau and Show Racer macrophage cultures. Media proteoglycans consisted of high-molecular-weight chondroitin sulfate proteoglycan, low-molecular-weight chondroitin sulfate proteoglycan, and heparan sulfate proteoglycan. High molecular-weight chondroitin sulfate proteoglycan was predominantly 6-sulfated (80%) and contained a core protein larger than 200 kd, whereas low-molecular weight chondroitin sulfate proteoglycan was 4-sulfated and contained a 28-kd core protein. Pericellular proteoglycan was similar in size to low-molecular-weight proteoglycan and consisted of a predominantly 6-sulfated (75%) chondroitin sulfate proteoglycan and heparan sulfate proteoglycan. Intracellular 35S-labeled chondroitin sulfate and heparan sulfate were smaller than media and pericellular proteoglycans, suggestive of intracellular degradative processing. PMID- 1613398 TI - Cationic defensins arise from charge-neutralized propeptides: a mechanism for avoiding leukocyte autocytotoxicity? AB - Defensins, small cationic polypeptides with antimicrobial and cytotoxic properties, are among the principal constituents of cytoplasmic granules of mammalian neutrophils and certain macrophages. To identify conserved structural features of defensin precursors that may be important for their targeting to cytoplasmic granules or for prevention of autocytotoxicity, we isolated and sequenced three neutrophil-specific rabbit defensin cDNAs that code for preproprotein precursors to the mature defensins NP-3a, NP-4, and NP-5. The preprodefensins NP-3a, NP-4, and NP-5, like the previously characterized preprodefensins, lack consensus sequences for N-linked glycosylation, suggesting that defensins are targeted to lysosome-like granules by a mechanism not dependent on the mannose-6-phosphate receptor. Analysis of all seven known myeloid prodefensins revealed a structure wherein an anionic propiece neutralizes the cationicity of the mature peptide. Because defensins apparently require cationic epitopes for cell membrane permeabilization and cytotoxicity, charge neutralization of mature peptides by their anionic propieces may prevent autocytotoxicity during defensin synthesis and processing. PMID- 1613399 TI - Interstitial pulmonary macrophages produce platelet-derived growth factor that stimulates rat lung fibroblast proliferation in vitro. AB - Alveolar macrophages from humans and several animal species produce factors in vitro that modulate fibroblast growth and have been proposed as mediators of interstitial pulmonary fibrosis. Pulmonary interstitial macrophages (IMs) have not been studied previously in this regard. Pulmonary IMs were isolated from prelavaged rat lungs by enzymatic digestion of tissue and subsequent differential adherence of cells to culture dishes. The ability of IMs to release modulators of fibroblast growth into the culture medium was assessed by measuring [3H]thymidine incorporation into DNA and/or nuclear labeling of early-passage rat lung fibroblasts exposed to medium conditioned by IMs. The percentages of nuclei labeled in fibroblast cultures exposed to interstitial macrophage-conditioned medium (IMCM) alone did not significantly differ from that observed in controls, but fibroblasts exposed to IMCM supplemented with 2% platelet-poor plasma showed a 2.6-fold increase in labeling, indicating that IMCM contains predominantly "competence" growth factor activity. Similar results were obtained using purified human platelet-derived growth factor (PDGF). The level of growth factor activity released by IMs increased in cells that had phagocytized iron spheres during the culture period. In addition, fractionation of IMCM by high-performance liquid chromatography demonstrated most of the growth factor activity at a relative molecular mass of about 35 kd. Subsequent quantitative analysis of the fractions by an enzyme immunoassay for PDGF demonstrated that IMCM contains a homologue of human PDGF. These results show that IMs are capable of producing a PDGF-like growth factor for autologous fibroblasts and that release of this factor is enhanced by exposure to an insoluble inorganic particle. Because PDGF is a potent growth factor for fibroblasts and is released by IMs, it is essential to ask in future studies whether this or similar macrophage products play a significant role in mediating fibroblast proliferation in vivo. PMID- 1613400 TI - [Transcranial pulsed Doppler. Problems posed by the temporal window (834 patients)]. AB - The absence of temporal windows represents an indisputable limitation of transcranial pulse Doppler (13% of 834 patients). We wanted to specify the elements causing this condition. The patient's age is a determinant factor, especially after 60 years of age. The sex also plays a role, as the window is absent in 23% of women and 6% of men. The use of one device as a rule (95%) does not allow appreciating the results according to the respective qualities of the various systems, which have been diversified as the study was in progress. On the other hand, the technician's experience (this person being experimented with the method) has no significant influence on the results. PMID- 1613401 TI - [Phlegmasia caerulea dolens . Acute venous stasis and ischemic phlebothrombosis]. AB - On the basis of the data of the literature and of 25 personal cases, the problem of phlegmasia caerulea is contemplated in its whole. Gregoire made an outstanding description of the condition in 1938; it was related to an arterial spasm, but later works showed the importance of the venous block and the secondary character of the arterial involvement. A severe form of venous thrombosis, phlegmasia caerulea dolens often occurs in elderly patients (11/25 in our series) or in persons in a poor general condition. The primary phenomenon is the occurrence, in various etiological circumstances, of an acute venous stasis giving rise to a number of phenomena, including extensive thrombosis and arterial involvement, which lead to irreversible lesions and to gangrene. Thus there is a first reversible phase of acute venous stasis with a still moderate arterial involvement, and a second phase of evolution with marketed ischemia, in which the tissular lesions can become irreversible. The necrosis results from the massive obliteration of the cutaneous venulae, not from the arterial failure. The old term of venous gangrene (Cruveilhier) points out to the mechanism and makes the practicioner aware of the extreme severity of any ischemic phlebitis, which can reach an irreversible stage within a few hours. The condition is therefore an emergency, and venous drainage must be re-established as quickly as possible in the limb, thus breaking the pathological cycle leading to irreversible lesions. In the simple venous stasis phase, a medical treatment may be attempted, but it must not be continued if it is not effective. Venous thrombectomy, a quick and safe procedure, therefore is the solution to choose either at once or after a short trial of medical treatment. Phlegmasia caerula certainly is the best indication for this procedure. If operated on time, the results are excellents: however, in very advanced cases with massive and total thrombosis of the venous system, amputation remains the only solution. PMID- 1613402 TI - [Mechanisms of action of medullary neurostimulation in the treatment of limb arteriopathy]. AB - Despite 25 years of clinical practice, concerning chronic epidural spinal cord stimulation (SCS) for pain control, the mechanisms underlying the beneficial effects are still poorly understood. The main indications for SCS are intractable chronic pain secondary to neurogenic origin (essentially neuropathies by lesion of peripheral nerve or roots) or to ischemic origin. Several observations suggest that mechanisms by which SCS alleviate these two types of pain are different. In peripheral vascular disease, the analgesic effect appears as the consequence of the vasodilatory effect of SCS. The actual experimental data indicate that SCS produce its influence on peripheral microcirculation via a transitory suppression of the sympathetic vasoconstrictor control. PMID- 1613403 TI - [Vascular exploration tests. Importance for the indications and monitoring of epidural medullary neuro-stimulation]. AB - The clinical diagnosis must be enriched by quantifiable parameters when a new therapeutic method must be tested. We analyse the role of vascular explorations for epidural stimulation and limb arteriopathies. Four different fields of investigations can be defined. Accuracy of the diagnosis: The tests are useful to rule out some differential diagnoses of arterial involvement, and to establish the functional severity (stage III). 1--Treadmill test: nonischemic pain is ruled out: the evolution can be followed up. 2--Doppler velocimetry demonstrates the extent of the dominant arterial involvement in cases of associated lesions. 3- Arterial pressure gradients: their presence demonstrates significant lesions and allows detecting the affected levels. Quantification of severity: After detecting the lesions, their impact must be appreciated. From a macrocirculatory point of view, the measurement of pressures and flow rates is more sensitive than the Doppler study. From a microcirculatory point of view, the tcpO2 is very useful. 1 -Arterial pressure: measured in the ankle and the first toe. There are three degrees: non-threatening ischemia (pulsatile Doppler, distal pressure exceeding 30 mm Hg), threatening ischemia (non pulsatile Doppler, distal pressure exceeding 30 mm Hg), irreversible ischemia (no more pulse, no more capillary flow). If there are arterial calcifications, the pressure in the toe must be measured. 2- Arterial flow rate: the average flow rate may be preserved in an arteriopathy, while the pulsatile rate is already degraded. Non invasive electromagnetic or nuclear magnetic resonance flowmeters measure the total muscular flow. Laser Doppler shows the cutaneous flow rate. 3--The tcpO2: normally greater than 60 mm Hg.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613404 TI - [Digital arteriopathies of the arms and their treatment by posterior spinal cord neurostimulation]. AB - Digital arteriopathies of the upper limbs are distinguished from those of the lower limbs by their rarity and their particular etiologies. Digital arteriopathies are defined as the presence of organic lesions causing stenosis and obstruction of the distal upper limb arteries: radial arteries, ulnar arteries, palmar arches, digital arteries. PMID- 1613405 TI - [Prevention of postoperative deep venous thromboses and pulmonary embolism. General, gynecologic and orthopedic surgery, March 8, 1991, Paris]. PMID- 1613406 TI - [Acute thrombosis of the brachial artery and beta-thalassemia-sickle cell anemia]. AB - The authors report about one case of left branchial arterial thrombosis in a 6 year-old child with thalassemia-sickle cell disease. In their opinion, although this hemoglobinopathy usually causes microthrombosis, its existence at the same time as that of the brachial thrombosis does not seem to be a coincidence. The actual origin of this disease remains to be found, as well as the role that thrombocytosis may play. The authors emphasize the relative rarity of thrombolytic arterial diseases in African Negroes and advise practitioners to recognize them, because their diagnosis, often established late in our climates, has severe consequences. PMID- 1613407 TI - [Chylothorax and chylous ascites following surgery of an inflammatory aortic aneurysm. Case report with review of the literature]. AB - Chylous ascites complicating surgery on the abdominal aorta is infrequent: we report one case associated with right chylothorax, secondary to the surgical cure of an inflammatory aortic aneurysm. Surgery for aneurysms causes 81% of all chylous ascites caused by injuries to the intestinal lymphatics or to their recipients, the left latero-aortic lymph nodes or the cisterna chyli. Upper or extensive dissections of the retroperitoneal space and difficult dissection of ruptured or inflammatory aneurysms are the cisterna chyli. Upper or extensive dissections of the retroperitoneal space and difficult dissection of ruptured or inflammatory aneurysms are the major etiological factors. Stasis and fibrosis, then the rupture of the lymphatics into the aneurysmal wall were described during inflammatory aneurysm: this lymphatic etiology might explain the inflammatory character of these aneurysms and entail a risk of lymphoperitoneal fistula when laying the aneurysmal wall flat. An early diagnosis must be established with paracentesis before any compressive, metabolic, immunological or septic complications occur. Continuous parenteral feeding and selective paracenteses dry out 80% of the postoperative chylous ascites. If the ascites persists after 4 to 6 week's conservative treatment, a peritoneojugular derivation or a direct lymphostasis may be contemplated, according to the patient's condition. PMID- 1613408 TI - [Horton's disease with involvement of the arterial trunks of the arms. Pathogenic role of anticardiolipin antibodies? Report of two cases]. AB - Diffuse arterial involvement in temporal arteritis is well known but the intimate mechanisms of vasculopathy is unknown. Recently the presence of anticardiolipin antibodies (aCL) has been recognized in giant cell arteritis. We report two cases of temporal arteritis with diffuse arterial involvement associated with aCL (axillary arteries in the two cases associated with femoral arteries in one). During corticosteroid and anticoagulant therapy, a rapid improvement was noted with regression of upper-limb ischemia. One month later, the aCL were absent. These cases confirm the presence of aCL in giant cell arteritis with diffuse arterial involvement. These antibodies might imply severe vascular damage and could play a role in pathogenesis of the vasculopathy of temporal arteritis. Their presence suggests the necessity of anticoagulant therapy at the beginning of corticosteroid therapy. PMID- 1613409 TI - Forces generated during spinal manipulative therapy of the cervical spine: a pilot study. AB - OBJECTIVE: To determine the forces imparted to the cervical spine using direct sampling methods during a clinical episode of spinal manipulative therapy. DESIGN: Quantitative study. SETTING: Human Performance Laboratory, University of Calgary. PARTICIPANTS: Two doctor/patient pairs. Patients were selected by the treating chiropractors from their existing patients pools. INTERVENTIONS: SMT to the cervical spine (toggle method) on three separate occasions over a 2-wk period. The clinical relevancy of the treatment was assessed via before and after measures of tissue compliance. MAIN OUTCOME MEASURE: a) Forces during manipulation: preload and peak forces. b) Duration of applied forces. RESULTS: a) Mean peak force = 117.7 N (+/- 15.6 N). b) Mean duration of force = 101.7 msec (+/- 14.7 msec). CONCLUSION: The forces obtained with direct sampling methods compare favorably to previous measurements obtained from indirect sampling techniques, yet the force duration times are smaller (faster) using the direct method. PMID- 1613410 TI - Doppler ultrasound diastolic flow analysis for the early identification of peripheral arterial disease. AB - OBJECTIVE: The viscoelastic mechanical compliance properties of the human arterial system were examined in 100 subjects with A-mode Doppler ultrasound diastolic flow analysis. This technique of diastolic flow analysis is utilized to identify early atherogenic peripheral arterial disease. The sensitivity of the commonly utilized standard traditional ultrasound pressure-grade pneumatic cuff examination will be increased when accompanied by the diastolic flow analysis technique. SETTING: Diastolic flow analysis will aid in the early identification of lower extremity vascular claudication when lumbar spinal canal stenosis and elevated cardiovascular risk factors are present. This examination may be performed in the office setting with standard A-mode Doppler ultrasound equipment along with the usual pneumatic cuff procedure. The standard ultrasound cuff examinations are based on pressure gradients to identify lower extremity arterial disease. The low level of sensitivity of this test requires arterial obstruction of at least 50% to be present before positive identification is possible. Pathological alterations of the arterial wall occur during the early stages of atherosclerotic disease, are reflected by reduced wall distensibility and may be quantified by Doppler ultrasound. SUBJECTS: Studied were a total of 100 subjects, 50 with arterial disease risk factors and 50 normal controls. All subjects were screened for aortic coarctation, myocardial infarction, tachyarrhythmia, aortic value stenosis and mitral prolapse. The risk group subjects were all smokers and had a mixed distribution of hypertension, hypercholesterolemia and hyperglycemia. The commonly utilized standard traditional ultrasound pneumatic cuff examination was negative in all subjects. Anthropometric measurements and percent body fat were also obtained. Arterial diastolic antegrade flow analysis was performed with Doppler ultrasound on each subject. RESULTS: This study demonstrated that the elevated vascular risk factor group had a mean arterial distensibility measurement of 4.4 +/- 5.0%, and the control group displayed a mean measurement of 20.0 +/- 6.0%. The 50 elevated risk factor subjects showed approximately 5 times greater arterial stiffness and were identified with significance at an F test level of (p less than .001). CONCLUSION: This arterial compliance evaluation procedure is shown to be a reliable sensitive indicator of early atherosclerotic disease prior to the development of obstructive arterial lesions. PMID- 1613411 TI - Using the Kaminski model for evaluating philosophical thought. AB - A model is proposed for the evaluation of philosophical thought generated within the chiropractic profession. This model is patterned after the Kaminski et al. model used to evaluate chiropractic procedures and practices. Decisions about the knowledge status of a philosophical query are made by following a flow chart. These decisions are made based on the query items' ability to be adequately defined, philosophical plausibility and survival of philosophical "testing." The query is assigned a status as to its adequacy in terms of philosophical knowledge. The model is demonstrated using example queries. Its applications are examined and problems of implementation are discussed. PMID- 1613412 TI - Conservative management of an L4-L5 left nuclear disk prolapse with a sequestrated segment. AB - A case report is discussed in which a clinically diagnosed case of an L4-L5 nuclear prolapse with a sequestrated fragment was verified by computerized axial tomography and magnetic resonance imaging at the initiation of the treatment period. It was treated with flexion-distraction manipulation, hot and cold fomentation, positive galvanism, a lumbosacral support, nutritional supplementation, abstinence from sitting and exercises. Four wk after initiation of treatment, the patient was asymptomatic. Eight wk after initiation of treatment, and 6 wk after the original scan, magnetic resonance imaging verified a reduction in the size of the prolapse within the vertebral canal. An 11 month follow-up examination indicated the patient had no exacerbations of her condition and all objective findings were negative. PMID- 1613413 TI - Chiropractic as a profession in Europe. PMID- 1613414 TI - Plain film radiology in chiropractic. PMID- 1613415 TI - Rotator cuff disease: current trends in orthopedic management. PMID- 1613416 TI - Oestrogen and progestogen synergistically stimulate human and rat osteoblast proliferation. AB - Oestrogens play an important role in bone metabolism; they preserve bone mass after the menopause. Their action in bone has recently been shown to be, partly, a direct one, as oestrogen receptors and their effects have been demonstrated in bone cells. The role of progestogens in bone metabolism is less clear. In this study it has been shown that 17 beta-oestradiol exerts only a small, although not significant, stimulatory action with regard to SaOS-2 human osteosarcoma cell proliferation. A pure progestogen (Org 2058) has no effect when added alone. In combination with 17 beta-oestradiol, however, it has a highly synergistic action on SaOS-2 cell proliferation. The same effect was observed in primary rat osteoblasts, showing that this synergism is a general phenomenon in osteoblastic cells. High numbers of oestrogen and progestogen receptors have been demonstrated in SaOS-2 cells, indicating that the effects of these steroids are mediated via the normal route of steroid receptors. These data provide a cellular basis for the clinically recognized positive effect of oestrogen/progestogen combinations on bone formation. PMID- 1613417 TI - Long-term effects of thyroid stimulating hormone and insulin on intracellular pH in FRTL-5 cells. AB - We have studied the chronic effects of TSH (100 microU/ml) and insulin (10 micrograms/ml) on intracellular pH (pH(i)) in FRTL-5 cells using the pH sensitive probe 2'7-bis (2-carboxyethyl-5'-6') carboxyfluorescein. FRTL-5 cells were cultured on Petri dishes either in the presence of 4H, ie. Coons F-12 containing cortisol (10 nM), transferrin (0.5 microgram/ml), glycyl-histidyl lysine acetate (10 ng/ml) and somatostatin (10 micrograms/ml), or with 4H + insulin (5H), 4H + TSH, or 4H + TSH + insulin (6H). pH(i) was measured in small groups of cells by microspectrofluorimetry both in the presence and absence of bicarbonate ions after cells had been deprived of serum for at least a day. In the absence of TSH, insulin and bicarbonate ions, pH(i) was 7.26 +/- 0.18 (mean +/- SD, n = 49) rising to 7.89 +/- 0.09 (n = 59) and 7.43 +/- 0.1 (n = 55) in the presence of TSH (4H + TSH) and insulin (5H) respectively. Addition of both insulin and TSH (6H) resulted in a pH(i) of 7.75 +/- 0.09 (n = 40). In the absence of TSH and insulin, but the presence of bicarbonate ions, pH(i) was 7.29 +/- 0.12 (mean +/- SD n = 47) rising to 7.72 +/- 0.07 (n = 59) in 4H + TSH and 7.48 +/- 0.08 (n = 60) in 5H. pH(i) in the presence of both TSH and insulin was 7.81 +/- 0.03 (n = 60). In conclusion, both insulin and TSH caused an intracellular alkalinization, TSH markedly so, even in the presence of bicarbonate ions. PMID- 1613418 TI - Thymic peptides and neuroendocrine-immune communication. PMID- 1613419 TI - Possible mechanisms for reduction of circulating concentrations of progesterone by interferon-alpha in cows: effects on hyperthermia, luteal cells, metabolism of progesterone and secretion of LH. AB - Experiments were performed to determine the mechanism by which recombinant bovine interferon-alpha I1 (rbIFN-alpha) causes an acute reduction in plasma concentrations of progesterone. In experiment 1, administration of a prostaglandin synthesis inhibitor blocked rbIFN-alpha-induced hyperthermia but did not prevent the decline in plasma concentrations of progesterone. The decline in progesterone concentrations caused by rbIFN-alpha was, therefore, not a direct consequence of the associated hyperthermia or of pathways mediated through prostaglandin synthesis. It is also unlikely that rbIFN-alpha acts to increase the clearance of progesterone since injection of rbIFN-alpha did not decrease plasma concentrations of progesterone in ovariectomized cows given an intravaginal implant of progesterone (experiment 2). In experiment 3, rbIFN-alpha did not affect basal and LH-induced release of progesterone from cultured luteal slices, indicating that rbIFN-alpha is unlikely to affect luteal function directly. Injection of rbIFN-alpha did, however, cause a decrease in plasma concentrations of LH in ovariectomized cows (experiment 4) that coincided temporally with the decrease in progesterone concentrations seen in cows having a functional corpus luteum. The present results strongly suggest that rbIFN-alpha acts to reduce secretion of progesterone by interfering with pituitary support for luteal synthesis of progesterone. The finding that rbIFN-alpha can inhibit LH secretion implies that interferon-alpha molecules should be considered among the cytokines that can regulate hypothalamic or pituitary function. PMID- 1613420 TI - Effect of food deprivation and altered thyroid status on the hypothalamic pituitary-thyroid axis in the rat. AB - Propylthiouracil (PTU) was administered to rats for different lengths of time with or without food deprivation on the last 2 days. Within 4 days of PTU treatment peripheral 3,5,3'-tri-iodothyronine (T3) fell to low levels and beta subunit of thyroid-stimulating hormone (beta-TSH) mRNA increased significantly in the anterior pituitary. Pro-thyrotrophin-releasing hormone (pro-TRH) mRNA in the hypothalamic paraventricular nucleus (PVN) increased significantly in the control group of animals by 8 days and in the food-deprived group by day 12; the increment of pro-TRH mRNA in the food-deprived group on day 12 was significantly less than that in the control group. In a second study, animals were treated with intraperitoneal injections of T3 with or without the food deprivation. After 4 days of T3 treatment, peripheral T3 levels were markedly increased and pro-TRH mRNA in the PVN and beta-TSH mRNA in the anterior pituitary were significantly reduced. Food deprivation had no additional suppressive effect. These studies confirm that the predominant effect of food deprivation on the thyroid axis is at the hypothalamic or suprahypothalamic level and that it can, at least in part, overcome the increase in TRH mRNA due to diminished T3 feedback. PMID- 1613421 TI - The anabolic effect of 17 beta-oestradiol on the trabecular bone of adult rats is suppressed by indomethacin. AB - We have previously demonstrated that administration of oestrogen, at doses sufficient to raise serum concentrations to those seen in late pregnancy, increases trabecular bone formation in the metaphysis of adult rats. To determine whether prostaglandins (PGs), which have been shown to induce osteogenesis in vivo, play a role in the induction of bone formation by oestrogen, 13-week-old female rats were given daily doses of 4 mg 17 beta-oestradiol (OE2)/kg for 17 days, alone or with indomethacin (1 mg/kg). The rats were also given double fluorochrome labels and at the end of the experiment tibias were subjected to histomorphometric assessment. Treatment with OE2 suppressed longitudinal bone growth and increased uterine wet weight, as expected, and neither response was affected by indomethacin. Oestrogen also induced a threefold increase in trabecular bone formation in the proximal tibial metaphysis, which resulted in a substantial increase in trabecular bone volume. As previously observed, the increase in bone formation was predominantly due to an increase in osteoblast recruitment (as judged by an increase in the percentage of bone surface showing double fluorochrome labels), with only a minor increase in the activity of mature osteoblasts (as judged by the mineral apposition rate). Indomethacin abolished the increase in osteoblastic recruitment, but the activity of mature osteoblastic cells remained high. The bone formation rate and bone volume remained similar to controls. The results suggest that PG production may be necessary for the increased osteoblastic recruitment induced by oestrogen, but not to mediate the effects of oestrogen on the activity of mature osteoblasts. PMID- 1613422 TI - Characterization and hormonal regulation of 24 kDa protein synthesis by the adult murine epididymis. AB - The pattern of labelled proteins synthesized and secreted in vitro by the adult mouse epididymis was studied by one- and two-dimensional polyacrylamide gel electrophoresis. The presence of a major 24 kDa protein synthesized and secreted in a tissue-specific manner by the caput epididymidis was detected. For this molecular weight, two-dimensional analysis indicated several proteins including two polypeptides (pI 8.4 and 8.8) whose expression is under androgenic control. Partial amino acid sequence analysis showed a complete N-terminal identity between these two peptides. A polyclonal monospecific immune serum was raised against the two proteins. Only purified immunoglobulins precipitated them, showing that immunological affinity is restricted to these two proteins in the epididymis. Indirect immunofluorescence assay revealed specific binding of antibodies on the acrosomal region of spermatozoa isolated from the caput, corpus or cauda epididymides. Testicular spermatozoa were not labelled under the same conditions. To investigate the physiological role of androgens in the synthesis and secretion of the 24 kDa proteins, tissue slices of epididymides from adult mice which had been castrated, or castrated then injected with testosterone were incubated with [35S]methionine. Castration and testosterone replacement kinetics revealed that alterations in 24 kDa protein synthesis follow immediately upon androgenic privation and replacement. PMID- 1613423 TI - A comparative analysis of the neuroendocrine mechanisms regulating ovulation, affected by a unilateral implant of atropine in the preoptic-anterior hypothalamic area, in intact and hemiovariectomized adult rats. AB - The effects were analysed of a unilateral implant of atropine on ovulation in intact and hemiovariectomized adult rats, together with the response of the atropine-implanted rats to hormone replacement. An outer cannula directed to the left or right preoptic (POA)-anterior-hypothalamic area (AHA) was implanted into cyclic adult rats. A group of animals in oestrus was hemiovariectomized and some were also implanted with a cannula. After two consecutive 4-day cycles, the hemiovariectomized animals were implanted with atropine (23 +/- 4 micrograms) or cholesterol (25 +/- 2 micrograms) on the day of oestrus. Atropine implanted into the left side of the POA-AHA blocked ovulation and compensatory ovarian hypertrophy, whilst implants in the right side had no effects. Administration of gonadotrophin-releasing hormone (GnRH; 3.7 micrograms/kg) at 13.00 h on the expected day of pro-oestrus induced ovulation in six out of seven treated animals. Of 19 rats with an implant of atropine in the left side of the POA-AHA, one ovulated after treatment with pregnant mare serum gonadotrophin (PMSG) on oestrus, or oestradiol benzoate or human chorionic gonadotrophin (hCG) on day 2 of dioestrus. The effects on ovulation of a unilateral implant of atropine into the POA-AHA of cyclic adult rats and the responses of such rats to GnRH, PMSG, hCG and oestradiol benzoate replacement were also studied. Ovulation was induced in rats with a unilateral implant of atropine and which had been treated with GnRH or hCG at 13.00 h on the expected day of pro-oestrus after the implant.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613424 TI - Effects of insulin-like growth factor-I and insulin on the in-vitro uptake of sulphate by eel branchial cartilage: evidence for the presence of independent hepatic and pancreatic sulphation factors. AB - The possible roles of insulin-like growth factor-I (IGF-I) and insulin in regulating cartilage growth were studied in the teleost Anguilla japonica. Significant sulphation activity was found in the extracts of pancreas, liver and muscle, but not in those of kidney, intestine or spleen. The hepatic sulphation activity was significantly decreased by hypophysectomy or by fasting for 14 days, suggesting that this activity is regulated by pituitary function and nutritional status. Northern blot analysis revealed that the hepatic IGF-I mRNA in the eel consists of a major 4.0 kb band. This mRNA was GH-dependent and was significantly decreased by fasting for 14 days. On the other hand, fasting for 14 days had no significant effect on pancreatic sulphation activity. Pancreatic extracts from both intact and hypophysectomized eels exhibited equally significant stimulating activity. Addition of bovine or human insulin (1-250 ng/ml) to the culture medium significantly stimulated sulphate uptake in a dose-dependent manner. Teleost (coho salmon) insulin was as effective as bovine insulin. Bovine insulin was more effective than IGF-I at lower concentrations (1-4 ng/ml) but less effective at higher concentrations (10-250 ng/ml). These results indicate that not only IGF-I but also insulin are likely to be involved in the regulation of cartilage growth in the eel. PMID- 1613425 TI - Eel insulin: isolation, characterization and stimulatory actions on [35S]sulphate and [3H]thymidine uptake in the branchial cartilage of the eel in vitro. AB - Our previous studies have shown that mammalian and salmon insulins stimulate sulphate uptake by cultured eel cartilage, suggesting the possible involvement of insulin in the regulation of cartilage matrix synthesis. In the present study, homologous eel insulin was isolated and characterized, and its effects on cartilage matrix synthesis and DNA synthesis were examined in vitro. Insulin was extracted from eel pancreas with acid-ethanol, and subsequently purified by isoelectric precipitation at pH 5.3, gel filtration on Sephadex G-50, and reversed-phase high-performance liquid chromatography. The amino acid composition and complete sequence (50 residues) of eel insulin revealed high homology to teleostean and mammalian insulins. The isolated eel insulin produced a more pronounced and longer lasting hypoglycaemic effect than bovine insulin in the eel. Homologous eel insulin, like bovine insulin-like growth factor (IGF-I) and insulin, stimulated sulphate uptake by cultured eel cartilage in a dose-dependent manner (16-1000 ng/ml). Combination experiments using maximal concentrations of bovine IGF-I (250 ng/ml) and increasing amounts of eel insulin (10-250 ng/ml) showed no additive effects of insulin on sulphate uptake, suggesting that insulin and IGF-I may share a common mechanism(s) of action. Eel insulin and bovine IGF-I also enhanced thymidine incorporation by eel cartilage in a dose-dependent manner (4-1000 ng/ml); eel insulin was equipotent with bovine IGF-I. These results suggest that insulin, like IGF-I, may exert direct growth-promoting actions in branchial cartilage of the eel. PMID- 1613426 TI - Testicular 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase in the hypophysectomized rat: effect of treatment with 5 alpha-dihydrotestosterone. AB - The in-vivo regulatory effect of androgens on steroidogenesis was investigated. Adult (2 to 3 months old) hypophysectomized rats were treated intratesticularly with increasing doses of 5 alpha-dihydrotestosterone (DHT; 10-200 micrograms/100 g body weight) or vehicle (50 microliters dimethyl sulphoxide; DMSO) in the contralateral testis. Intratesticular testosterone concentrations were extremely low in hypophysectomized rats 15-20 days after surgery. Treatment with DHT caused a dose-dependent inhibition of testicular 3 beta-hydroxysteroid dehydrogenase/delta 5-4 isomerase (3 beta-HSD) 2 h later, and this effect was apparent at the dose of 20 micrograms/100 g body weight (P less than 0.01). The inhibitory effect of 3 beta-HSD was not due to a possible interference of DHT in the enzyme assay, since various concentrations of the androgen (0.1-100 mumol/l) were ineffective as inhibitors of 3 beta-HSD. The highest dose of DHT used in this study (200 micrograms/100 g body weight) resulted in a rapid (1-2 h) and transient (4-6 h) inhibition (approximately 80%) of 3 beta-HSD activity. Pretreatment of rats with the antiandrogen cyproterone acetate (5 mg/rat) or the protein synthesis inhibitor cycloheximide (10 mg/rat) did not affect the enzyme activity of testes injected with DMSO, but counteracted the inhibitory effect of DHT on 3 beta-HSD activity in the contralateral testis. The results presented suggest that the inhibitory effect of the non-aromatizable androgen DHT is receptor-mediated and involves the synthesis of a factor(s) that modulates 3 beta HSD activity. PMID- 1613427 TI - Vasoactive intestinal peptide stimulation of aldosterone secretion by the rat adrenal cortex may be mediated by the local release of catecholamines. AB - The effects of vasoactive intestinal peptide (VIP) on adrenocortical function were investigated using several different preparations of adrenocortical tissue. VIP caused a significant increase in perfusion medium flow rate and in aldosterone and corticosterone secretion by the isolated perfused rat adrenal gland, with a threshold of 1 pmol in 200 microliters, but did not affect basal steroid secretion by collagenase-dispersed adrenocortical cells at any concentration used, from 10 pmol/l to 10 mumol/l. The presence of VIP (100 nmol/l) had no significant effect on the response of zona glomerulosa cells to stimulation by ACTH at any concentration. In incubations of intact adrenal capsular tissue, VIP (10 mumol/l) caused a significant stimulation of aldosterone secretion, and also induced a significant release of adrenaline into the incubation medium. Addition of (-)alprenolol (100 nmol/l), a beta-adrenergic antagonist, to the incubation medium significantly attenuated the response of capsular tissue to VIP. It is concluded that the effects of VIP on aldosterone, which are only seen when the architecture of the zona glomerulosa is preserved, may be mediated by the local release of adrenaline. PMID- 1613428 TI - Functional maturation of arginine vasotocin secretory responses to osmotic stimulation in the chick embryo and the newborn chicken. AB - The time-course of appearance of plasma vasotocin and the ontogeny of the vasotocin response to osmotic stimulation during embryonic development was examined in the chicken. In the first experiment, blood was obtained by heart puncture of chicken embryos on embryonic days (E) 15-20, and by decapitation of chickens on the day of hatching (D1 = E21). Plasma was separated for measurement of osmolality and vasotocin. Basal plasma osmolality remained constant until E20 (285-291 mosmol/kg) and was significantly increased at D1 (304 +/- 2 mosmol/kg). Plasma vasotocin was first detectable at E16 (5.5 +/- 0.8 (S.E.M.) pmol/l) and increased thereafter with a peak at E18 (21.8 +/- 2.3 pmol/l). The concentration decreased again at D1 (9.0 +/- 1.7 pmol/l). Osmotic stimulation with hypertonic NaCl 60 min before the animals were killed in the second experiment increased plasma osmolality, at all time points, by 9 +/- 0.2 mosmol/kg in all animals, but increased vasotocin in an age-dependent manner. The vasotocin response was greatest in D1 chickens, and the increase in vasotocin concentration relative to the control group value was 61 pmol/l, whereas the corresponding value in young (E15-E18) and older (E19-E20) embryos was only approximately 9 and 18 pmol/l respectively. In a third experiment the time-course of vasotocin secretion after osmotic stimuli in catheterized chickens (E18 and D1) was established. The basal plasma osmolality was significantly increased after 15 min in both groups. Vasotocin levels were significantly raised after 15 min in E18 and after 30 min in D1 chickens and further increased thereafter.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613429 TI - Effects of dopamine, high potassium concentration and field stimulation on the secretion of aldosterone by the perfused rat adrenal gland. AB - The rat adrenal cortex contains quantities of dopamine that are compatible with its function as a neurotransmitter, suggesting that locally released dopamine may act as a neuroregulator within the gland. This possibility has been tested by comparing the effects of dopamine on aldosterone secretion in the perfused adrenal with the effects of stimuli designed to provoke the release of intraglandular dopamine. Infusion of dopamine (0.1-100 mumol/l for 10-min periods) into the isolated perfused rat adrenal gland resulted in a transient, dose-related reduction of aldosterone secretion to a minimum of approximately 50% of the basal value at 1 mumol dopamine/l (ratio of experimental to control measurements, R = 0.53 +/- 0.06 (S.E.M.); n = 5). In contrast, dopamine (1-100 mumol/l) had no effect on aldosterone production by dispersed zona glomerulosa cell preparations incubated in vitro. The effects of changes in K+ concentration (3.9-52 mmol/l) on aldosterone secretion in the perfused gland and dispersed cell preparations were also compared. A similar bell-shaped dose-response relationship was seen in both preparations between 6 and 32 mmol K+/l, with a maximum at 8.4 mmol K+/l and a return to control values with 16, 24 or 32 mmol K+/l. However, infusion of media with very high K+ concentrations (42 or 52 mmol K+/l) reduced the secretion of aldosterone by the perfused gland to approximately 50% of the basal value (R = 0.51 +/- 0.05, n = 9; R = 0.49 +/- 0.08, n = 9; respectively) but produced no change in aldosterone production by zona glomerulosa cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613430 TI - Daily rhythms in the hormone content of the neurohypophysial system and release of oxytocin and vasopressin in the male rat: effect of constant light. AB - Patterns of neurohypophysial hormone secretion and changes in the hormone content of the hypothalamus and posterior pituitary lobe were monitored in the male rat for cycles of 24 h in association with changes in food and water intake and fluid excretion. Plasma oxytocin and vasopressin concentrations were seen to rise significantly over the hours of daylight, decreasing during the night. Parallel changes were seen in the immunoreactive material in the hypothalamus, whilst the content of the neurohypophysis was inversely related to plasma concentrations. The ratio of plasma oxytocin:vasopressin reached a significant peak at about 02.00 h which might be related to the feeding activity of the rats, food and water intake being largely confined to the night, as was fluid excretion. On exposure to constant light, despite initial disruption hormonal rhythms were still seen but showed a phase shift. The relationships between plasma and tissue levels were maintained. Patterns of food and water intake and urinary excretion were little affected by exposure to constant light, remaining largely confined to the former night phase. The hormonal rhythms appeared to be more closely related to the activity of the rats, which also showed a phase shift during constant light. PMID- 1613431 TI - Effect of growth hormone and insulin-like growth factor-I on DNA synthesis and matrix production in rat epiphyseal chondrocytes in monolayer culture. AB - The influence of various culture conditions was studied on the effect of GH and insulin-like growth factor-I (IGF-I) on DNA and matrix synthesis in epiphyseal rat chondrocytes in monolayer culture. Chondrocytes from enzymatically digested rat tibia epiphyseal growth plates were seeded in 48-well culture plates and precultured for 10 days in Ham's F-12 medium supplemented with 1% (v/v) newborn calf serum and 1% (v/v) of a serum substitute. After preculture, the medium was changed to Ham's F-12 medium supplemented with 1% serum from hypophysectomized rats, and the effect of GH and IGF-I on DNA synthesis ([3H]thymidine incorporation) and matrix production ([35S]sulphate uptake) was studied during an additional 96-h culture period. Isotopes were present during the last 24 h of culture. Both hGH and IGF-I stimulated DNA synthesis in a dose-dependent manner. A maximal effect of GH was seen at a concentration of 25 micrograms/l (60 +/- 11% stimulation over control) and for IGF-I at 10 micrograms/l (162 +/- 12%). The stimulatory effects of the same concentrations of human GH (hGH) and IGF-I on [35S]sulphate uptake were 135 +/- 25 and 320 +/- 42% respectively. In-vitro pulse labelling revealed that GH did not produce a response during the first 3 days of culture (after addition of GH) but was effective during days 4 and 5 of culture. In contrast, IGF-I was effective throughout the culture period. Pretreatment of cells with GH or IGF-I for 2.5 days showed that GH but not IGF-I produced a sustained effect on [3H]thymidine uptake. In order to study the influence of cell density on the effect of GH and IGF-I on DNA synthesis, the effect of added peptides was evaluated after different preculture periods (5-15 days). A maximal stimulatory effect of hGH was seen at a cell density of 150,000-300,000 cells/cm2. GH had no significant effect at a low (less than 100,000 cells/cm2) or a high (greater than 400,000 cells/cm2) cell density. The magnitude of the stimulatory effect of IGF-I was the same at densities between 10,000 and 250,000 cells/cm2, but was reduced at higher cell densities (over 250,000 cells/cm2). Chondrogenic properties of cells that had been cultured for 15 days were verified in vitro by positive alcian blue staining and identification of type II collagen, and in vivo by development of cartilage nodules in nude mice.(ABSTRACT TRUNCATED AT 400 WORDS) PMID- 1613432 TI - Effect of type 1 transforming growth factor-beta on the level of aromatase cytochrome P-450 in human fetal hepatocytes. AB - Aromatase cytochrome P-450 (P-450AROM) is the enzyme in the steroidogenic pathway controlling the formation of oestrogens from 19 carbon steroid precursors. Aromatase is present in various tissues of the human fetus. The liver is second only to the placenta in the level of P-450AROM activity in the fetus. In this study we examined the effects of type 1 transforming growth factor-beta (TGF beta) on P-450AROM expression in human fetal (HF) hepatocytes. The HF hepatocytes were dispersed into single cells which were placed into monolayer cell culture until confluent. Cells were then rinsed and treated in serum-free media with dibutyryl cyclic AMP (Bu2cAMP) for 72 h. Treatment with Bu2cAMP (2 mmol/l) caused a fivefold increase in aromatase activity in hepatocytes. The increase in aromatase activity apparently represented an increase in P-450AROM enzyme as determined by immunoblotting using an antibody directed against human placental aromatase. TGF beta blocked basal, as well as Bu2cAMP increases, in aromatase activity by over 50%. The effect of TGF beta was dose-dependent with maximal inhibition observed using 2-5 ng TGF beta/ml. Immunodetectable P-450AROM decreased in parallel with activity following TGF beta treatment. The mechanism of TGF beta action was not through increasing phosphodiesterase (PDE) breakdown of cAMP since inhibition of PDE had no effect on TGF beta action. Finally we examined the level of P-450AROM mRNA using competitive polymerase chain reaction amplification. Bu2cAMP increased mRNA levels of P-450AROM by 2.5-fold, while TGF beta inhibited this induction by 35%. The results of this investigation demonstrated that TGF beta is a potent regulator of P-450AROM expression in HF hepatocytes. PMID- 1613433 TI - Sex and smell--an enigma resolved. PMID- 1613434 TI - Tri-iodothyronine stimulates rat osteoclastic bone resorption by an indirect effect. AB - Tri-iodothyronine (T3) increases bone resorption in vivo and in vitro. In order to understand further the mechanisms by which this occurs we studied the effects of T3 at concentrations in the range of 1 pmol/l-1 mumol/l on bone resorption by osteoclasts isolated from neonatal rat long bones. Osteoclasts were disaggregated and incubated either with or without UMR 106 cells or with mixed bone cells. We found that there was no effect of T3 on bone resorption by osteoclasts incubated alone or co-cultured with UMR 106 cells. However, in culture with mixed bone cells there was a significant relationship between the concentration of T3 and bone resorption (r = 0.54, P = 0.01). The greatest effect was observed at a T3 concentration of 1 mumol/l at which a 1.8-fold increase in resorption was seen compared with control (P less than 0.005; paired t-test). We conclude that the ability of T3 to increase osteoclastic bone resorption is not due to a direct action of T3 on osteoclasts but is mediated by another cell present in bone. The observation that UMR 106 cells are unable to mediate this effect suggests that either the mediating cell is not osteoblastic or the phenotype of UMR 106 does not conform to the phenotype of osteoblastic cells that mediate the T3 responsiveness of bone. PMID- 1613435 TI - Immunoneutralization and immunocytochemical localization of inhibin alpha subunit during the mid-luteal phase in the stump-tailed macaque. AB - The putative endocrine role of inhibin in the control of FSH secretion during the luteal phase in the primate was investigated by immunoneutralization. Antisera against the 1-23 amino acid sequence of the N-terminus of the human inhibin alpha subunit were raised in a ewe and three macaques. Antisera (10-20 ml) were administered to macaques on day 8/9 of the luteal phase and serum samples collected during the treatment cycle and post-treatment cycle for determination of FSH, oestradiol and progesterone. In addition, localization of inhibin within the macaque ovary at this stage of the luteal phase was investigated using the ovine antiserum. Intense immunostaining was localized within the granulosa-lutein cells of the corpus luteum with absence of staining in the theca-lutein cells or other ovarian compartments. Administration of antisera was without significant effect on serum concentrations of FSH when compared with control animals, either during the first 24 h of detailed observation or for the following 10-day period of the late luteal phase and subsequent early follicular phase. These results provide further evidence that the corpus luteum is the major source of inhibin immunoreactivity during the primate menstrual cycle, but fail to support an endocrine role for inhibin in the suppression of FSH secretion. PMID- 1613436 TI - Expression and translation of the growth hormone-receptor gene in the guinea-pig. AB - The refractoriness of guinea-pigs to the growth-promoting actions of exogenous GH has been suggested to be due to a deficiency or defect in tissue GH receptors or in GH-receptor gene expression. GH-receptor mRNA was, however, demonstrated by Northern blot analysis and by the polymerase chain reaction in extracts of guinea pig liver, adipose tissue, brain, hypothalamus and pituitary gland. High affinity, low-capacity binding sites for radio-labelled ovine GH were also demonstrated on the plasma membranes of guinea-pig liver and were similar to those in rat liver. These results demonstrate that the unresponsiveness of guinea pigs to exogenous GH is not due to the absence of GH receptors. PMID- 1613437 TI - Control of protein and matrix-molecule synthesis in isolated ovine fetal growth plate chondrocytes by the interactions of basic fibroblast growth factor, insulin like growth factors-I and -II, insulin and transforming growth factor-beta 1. AB - Chondrogenesis is thought to be controlled by interactions between circulating anabolic hormones and locally produced peptide growth factors, and involves ordered changes in matrix composition which ultimately allow endochondral calcification. We have used a model of isolated ovine fetal growth-plate chondrocytes to examine the actions and interactions of basic fibroblast growth factor (basic FGF), insulin-like growth factors-I and -II (IGF-I and -II), insulin and transforming growth factor-beta 1 (TGF-beta 1) on total protein, collagen or non-collagenous protein and sulphated glycosaminoglycan synthesis. These parameters were determined by assessment of the incorporation by monolayer cultures of early passage chondrocytes of [3H]leucine, [14C]proline and [35S]sulphate respectively, followed by partial molecular characterization. Basic FGF enhanced total protein synthesis with a half-maximal effective concentration of 270 +/- 60 pmol/l (mean +/- S.E.M., four animals) and was sixfold more active on a molar basis than IGF-I or insulin, and 28-fold more active that IGF-II which is the endogenously synthesized IGF. The actions of basic FGF were additive to those of IGF-I or insulin. More detailed analysis of extracellular-matrix component synthesis showed that basic FGF, IGF-I and insulin each caused significant increases in the synthesis of collagen and sulphated glycosaminoglycans. TGF-beta 1 had no effect on total protein synthesis by chondrocytes when present alone at concentrations of 200 pmol/l or less, but was inhibitory at 400 pmol/l. However, the use of this parameter masked a stimulatory action of 50 or 100 pmol TGF-beta 1 on sulphated glycosaminoglycan synthesis and a relative shift in the ratio of collagen: non-collagenous protein synthesis in favour of the former. A synergistic interaction existed between TGF-beta 1 (20 100 pmol/l) and basic FGF which potentiated total protein and collagen synthesis, and their actions on sulphated glycosaminoglycan production were additive. The same concentrations of TGF-beta 1 inhibited the ability of IGF-I or insulin to stimulate total protein or collagen synthesis, but were additive to their stimulatory effects on sulphated glycosaminoglycan synthesis. The results suggest that matrix-molecule composition and the anabolic status of the epiphyseal growth plate may be modulated in utero by multiple interactions between peptide growth factors produced locally, such as basic FGF, IGF-II and TGF-beta 1, and circulating hormones such as insulin and IGF-I. PMID- 1613438 TI - The effects of hypo- and hyperthyroidism on fibre composition and mitochondrial enzyme activities in rat skeletal muscle. AB - Hypo- and hyperthyroidism have been associated with changes in the activities of mitochondrial enzymes in homogenates of skeletal muscles, but it is unclear whether such changes were due to changes in single fibre enzyme activities or to previously documented changes in relative numbers of fibres. In this study the activities of the mitochondrial enzymes alpha-glycerol phosphate dehydrogenase (m alpha GPDH) and succinate dehydrogenase (SDH) were measured in single fibres of the soleus and gastrocnemius muscles of the rat by cytochemical assays. In the soleus muscles of hypothyroid animals there was a decrease in the mean percentage (+/- S.D.) of type II fibres from 8.0 +/- 6.0 to 0.8 +/- 1.9% (P less than 0.05) and decreases in SDH activities in all fibre types (P less than 0.005). In the gastrocnemius muscles of these animals there were no changes in fibre composition but type IIB fibres had reduced (P less than 0.05) m-alpha GPDH activities. In the hyperthyroid animals, in which body weight had increased relative to the euthyroid animals, there were increases in the percentages of type IC and type II fibres in the soleus from 4.3 +/- 1.7 to 13.1 +/- 9.0% (P less than 0.05) and from 9.6 +/- 7.2 to 33.4 +/- 9.6% (P less than 0.005) respectively and an increase in the percentage of type IIA fibres in the gastrocnemius from 92.9 +/- 2.3 to 97.0 +/- 2.9% (P less than 0.05). However, there were no increases in single fibre mitochondrial enzyme activities.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613439 TI - The role of inhibin and oestradiol in the control of FSH secretion in the sheep. AB - The relative importance of inhibin and oestradiol in the control of FSH and LH secretion in the ewe was investigated by passive immunization in intact animals and by hormone replacement therapy following acute ovariectomy, in the same experiment. Mature Scottish Blackface ewes on day 10 of the luteal phase were allocated to nine groups of four to five animals. Four groups were ovariectomized and immediately treated with either progesterone alone or in combination with steroid-stripped ovine follicular fluid ('inhibin') and/or oestradiol. Three further groups of ewes were left intact and injected with antibodies to the 1-26 alpha peptide fragment of porcine inhibin and/or oestradiol-17 beta. Two groups of animals were either ovariectomized alone with no further treatment, or were left intact and treated with normal sheep plasma to act as controls. Blood samples were collected at 2 h intervals from 12 h before until 48 h after ovariectomy/immunization, and from 12 to 24 h after treatment, blood samples were collected at 10-min intervals. After ovariectomy there was a large rise in the peripheral concentration of LH (P less than 0.001) which was not affected by treatment with progesterone alone but was completely prevented by treatment with progesterone and oestradiol. Treatment with inhibin had no effect on this post castrational rise in LH. In intact ewes, immunization against oestradiol, alone or in combination with inhibin, resulted in a rise in the concentration of LH, while immunization against inhibin had no effect on LH concentration. The peripheral concentration of FSH showed a significant (P less than 0.001) increase after ovariectomy which was not affected by treatment with progesterone alone. Treatment with inhibin or oestradiol alone caused a significant (P less than 0.01) reduction in this rise, while treatment with inhibin and oestradiol together completely prevented this post-castrational rise in FSH concentration. Passive immunization against inhibin or oestradiol alone resulted in a transitory (P less than 0.01) rise in the peripheral concentration of FSH, while immunization against the two hormones in combination resulted in a significantly (P less than 0.01) larger rise. During the 14-h period after treatment, the rise in the concentration of FSH in this combined immunization group was not significantly different from that seen in the control ovariectomized group. These results provide evidence that FSH secretion is under the control of both oestradiol and inhibin, while reinforcing the hypothesis that inhibin is not involved in the regulation of LH production, which is under the dual control of oestradiol and progesterone. PMID- 1613440 TI - Somatolactin, a novel pituitary protein: purification and plasma levels during reproductive maturation of coho salmon. AB - Somatolactin (SL), a newly discovered fish pituitary protein belonging to the GH/prolactin family, was isolated from coho salmon (Oncorhynchus kisutch). Antibodies were raised to purified coho SL, and a homologous radioimmunoassay was developed and validated. The assay was specific for SL as indicated by the absence of cross-reactivity with coho salmon GH, gonadotrophins I and II and less than 0.2% cross-reaction to prolactin. Serial dilutions of plasma and pituitary extracts from Oncorhynchus species including coho salmon, chinook salmon and rainbow trout were parallel to the coho salmon SL standard curve. Displacement curves for dilutions of Atlantic salmon (Salmo salar) plasma, but not pituitary extract were parallel to the standards. Plasma levels of SL were measured in coho salmon throughout the final year of reproductive maturation. During the period of gonadal growth, plasma SL levels increased and were highly correlated to oestradiol levels in females and 11-ketotestosterone levels in males. Peak levels of SL were observed at the time of final maturation and spawning in both sexes. It is hypothesized that SL may regulate some physiological aspect of reproduction. PMID- 1613441 TI - Enhancement of noradrenaline-induced inositol polyphosphate formation by glucocorticoids in rat vascular smooth muscle cells. AB - Glucocorticoids are known to regulate the contractility of vascular smooth muscle by increasing its response to noradrenaline. The molecular mechanisms for achieving this remain unclear. Recent results in our laboratory have demonstrated that glucocorticoids affect both alpha 1-adrenoceptor number and coupling to G proteins. Whether this leads to an increase in second-messenger production has to be established. The present experiments, therefore, report the effects of dexamethasone on inositol polyphosphate production in vascular smooth muscle cells in culture. Noradrenaline induced the release of inositol polyphosphates from prelabelled [3H]inositol phosphoinositides in the membrane in a dose dependent manner. The concentration of noradrenaline which caused half-maximal response was 1.26 mumol/l. Prazosin inhibited noradrenaline-induced inositol monophosphate formation to 10.26 +/- 3.67% (mean +/- S.E.M.; P less than 0.01, n = 5) of control value whereas yohimbine reduced it to only 61.74 +/- 11.82% (P less than 0.05, n = 5), suggesting an action primarily through alpha 1-adrenergic receptors. Dexamethasone (100 nmol/l, 48 h) enhanced noradrenaline-induced inositol monophosphate, bisphosphate and trisphosphate formation up to twofold (P less than 0.001, n = 5). The enhancement of the response occurred despite the fact that dexamethasone reduced [3H]inositol prelabelling of membrane phosphoinositides by 49.5 +/- 9.9% (P less than 0.05, n = 3). The present results suggest that the potential action of glucocorticoids on vascular smooth muscle contractility is, at least in part, through controlling alpha 1-adrenoceptor mediated second-messenger production. PMID- 1613442 TI - Preovulatory follicle development and luteal function in ewes immunized against a synthetic peptide sequence of the alpha subunit of bovine inhibin. AB - Immunization against inhibin consistently results in an increase in ovulation rate in sheep, but the effects that this treatment has on follicle development are unknown. In order to determine the influence of inhibin, parameters of follicle development were assessed in ewes that had been actively immunized against a synthetic peptide homologous to the N-terminal sequence (alpha 1-29, Tyr30) of the alpha subunit of bovine inhibin, a treatment that neutralizes the biological activity of endogenous inhibin. The final stages of preovulatory follicle development that culminate in ovulation were induced in seasonally anoestrous ewes, and follicles were recovered prior to the predicted time of ovulation. After priming with progestagen, inhibin-immunized and control ewes were treated with gonadotrophin-releasing hormone (GnRH) by continuous infusion (200 ng/h). The ovaries were recovered at slaughter 24 h after the start of GnRH treatment and all follicles greater than or equal to 2.0 mm diameter were dissected out and their capacity to produce oestradiol in vitro was assessed. Further groups of similarly treated animals were blood-sampled daily to determine luteal function following GnRH-induced ovulation. The ovaries were recovered from these ewes at slaughter 10 days after the start of GnRH treatment, the corpora lutea were dissected out and their progesterone content was assessed. There were more (P less than 0.01) follicles of 5-6 mm diameter (3.2 +/- 0.45 (S.E.M.) compared with 1.1 +/- 0.25 follicles/ewe) and more (P less than 0.001) follicles of greater than 6 mm diameter (2.8 +/- 0.56 compared with 0.9 +/- 0.17 follicles/ewe) in inhibin-immunized than in control ewes.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613443 TI - Insulin-like growth factor-I and its N-terminal modified analogues induce marked gut growth in dexamethasone-treated rats. AB - The effects of insulin-like growth factor-I (IGF-I) on the gut of 150 g dexamethasone-treated rats were compared with those of two analogues with reduced affinity for IGF-binding proteins, des(1-3)IGF-I and LR3IGF-I, an N-terminal extended variant. Administration of IGF-I for 7 days to rats made catabolic by co treatment with dexamethasone induced a dose-dependent increase in total gut weight, with the highest dose of IGF-I (695 micrograms/day) increasing gut weight by up to 60%, and gut weight as a fraction of body weight by up to 32%. Effects were apparent in all regions of the gut examined, including the stomach, small intestine and colon. Histological and biochemical analyses of the intestine showed that cross-sectional mass, rather than gut length, was increased, and proportional increases in wet weight, protein and DNA content per unit length were measured in both the mucosa and muscularis layers. The rate of duodenal protein synthesis measured on day 7 of treatment was not increased by IGF-I treatment. The IGF-I analogues had qualitatively similar effects to IGF-I, but were consistently severalfold more potent, providing evidence that IGF-binding proteins reduce the biological activity of exogenous IGF-I in the gut. The results indicate that the gut is one of the most sensitive IGF-I target tissues, and that potency in vivo correlates with a reduced interaction with IGF-binding proteins. PMID- 1613444 TI - Vasoactive intestinal peptide inhibits the steroid-induced LH surge in the ovariectomized rat. AB - The LH surge was induced in ovariectomized rats by sequential treatment with oestradiol benzoate and progesterone. Vasoactive intestinal peptide (VIP) or saline was infused into the third cerebral ventricle from 13.30 to 16.30 h on the afternoon of the anticipated LH surge. Two blood samples were taken by jugular puncture from each animal, one at 12.00 h as a control sample and the other at 16.00, 18.00, 20.00 or 22.00 h. Saline-infused animals showed a normal LH surge, with mean plasma LH concentrations reaching a peak at 18.00 h, declining by 20.00 h and reaching control (12.00 h) levels by 22.00 h. Plasma LH in animals infused with VIP was not significantly higher than control levels at 16.00 or 18.00 h. By 20.00 h, mean LH levels in VIP-infused rats had risen to the levels seen at that time in saline-infused rats, and by 22.00 h LH had returned to control levels in VIP-infused animals. We interpret these findings to mean that VIP inhibits LH secretion during the LH surge. It does not block the surge completely, as pentobarbital during the critical period would have done; nor does VIP appear to affect the timing of the LH surge. Rather, VIP inhibits the increased LH secretion rates of the LH surge only during the period of VIP treatment and for a short time afterward. PMID- 1613445 TI - Exogenous gonadotrophin-releasing hormone (GnRH) stimulates LH secretion in male monkeys (Macaca fascicularis) treated chronically with high doses of a GnRH antagonist. AB - We reported previously that after a single injection of a gonadotrophin-releasing hormone (GnRH) antagonist to male monkeys, exogenous GnRH stimulated LH secretion in a time- and dose-dependent manner, indicating that GnRH antagonist-induced blockade of LH secretion resulted from pituitary GnRH receptor occupancy. The present study was performed to investigate whether GnRH can also restore a blockade of LH and testosterone secretion during chronic GnRH antagonist administration. Four adult male cynomolgus monkeys (Macaca fascicularis) received daily s.c. injections of the GnRH antagonist [N-Ac-D-pCl-Phe1,2,D-TRP3,D-Arg6-D Ala10]-GnRH (ORG 30276) at a dose of 1400-1600 micrograms/kg for 8 weeks. Before the GnRH antagonist was given and during weeks 3 and 8 of treatment, pituitary stimulation tests were performed with 0.5, 5, 50 and 500 micrograms synthetic GnRH, administered in increasing order at intervals of 24 h. At 8 weeks, a dose of 1000 micrograms GnRH was also given. All doses of GnRH significantly (P less than 0.05) stimulated serum concentrations of bioactive LH (3- to 8-fold) and testosterone (2.6- to 3.8-fold) before the initiation of GnRH antagonist treatment. After 3 weeks of GnRH antagonist treatment, only 50 and 500 micrograms GnRH doses were able to increase LH and testosterone secretion. Release of LH was significantly (P less than 0.05) more elevated with 500 micrograms compared with 50 micrograms GnRH. After 8 weeks, only the highest dose of 1000 micrograms elicited a significant (P less than 0.05) rise in LH secretion. Basal hormone levels just before the bolus injection of GnRH were similar (P greater than 0.10 0.80).(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613446 TI - What is a normal stimulated growth hormone concentration? AB - In a retrospective analysis, we have compared the response of serum GH concentration to insulin-induced hypoglycaemia in 148 short prepubertal children (114 males, 34 females) aged between 3.9 and 11.9 years with the growth rate of the individual to determine 'cut-off' values for the diagnosis of GH insufficiency. Sixty-three children grew with a height velocity standard deviation score (SDS) greater than -0.8 (group 1), which represents the growth velocity of children progressing along or closely parallel to the third height centile. Eighty-five children had a height velocity SDS of less than -0.8 (group 2). Median peak serum GH concentration responses to insulin-induced hypoglycaemia were 19.9 mU/l (range 1.5-54.4) in group 1 and 9.9 mU/l (range 0.7-46.2) in group 2 (Mann-Whitney; P less than 0.001). Using growth rate as the determinant of normality, the efficiency, sensitivity and specificity of the insulin-induced hypoglycaemia test were calculated using different serum GH concentration cut-off values to diagnose GH insufficiency. In our (Hybritech) assay, a cut-off value of 13.5 mU/l provided optimal performance in terms of efficiency (66%), sensitivity (64%) and specificity (70%). The response of serum GH concentration to insulin induced hypoglycaemia in short children growing at different growth rates was continuous. Each laboratory measuring serum GH concentrations needs to construct its own 'normal' cut-off value. PMID- 1613447 TI - Prostaglandin F2 alpha- and phorbol 12-myristate-13-acetate-stimulated progesterone production by cultured human luteal cells in the mid-luteal phase: prostaglandin F2 alpha increases cytosolic Ca2+ and inositol phosphates. AB - While prostaglandin F2 alpha (PGF2 alpha) has been thought to be a natural luteolysin in non-primates, a luteolytic effect in the human corpus luteum is less evident. We therefore investigated the action of PGF2 alpha on monolayer cultures of human luteal cells obtained from mid-luteal phase corpora lutea. PGF2 alpha increased basal and human chorionic gonadotrophin (hCG)-stimulated progesterone production by human cultured luteal cells. A potent tumour-promoting phorbol ester, phorbol 12-myristate-13-acetate (PMA), also stimulated progesterone production by cultured human luteal cells. Although human luteal cells were incubated for 24 h with PMA, hCG was still able to stimulate the production of progesterone by PMA-pretreated cells. However, PMA pretreatment blocked the ability of PGF2 alpha to stimulate progesterone production. It is possible that the luteotrophic effect of PGF2 alpha may be mediated, in part, by the activation of protein kinase C. Addition of PGF2 alpha to suspensions of human luteal cells preincubated with myo-[2-3H]inositol promoted an increase in labelled inositol phosphates. PGF2 alpha also rapidly increased intracellular free Ca2+ in human luteal cells loaded with the fluorescent Ca2+ probe, fura-2. We conclude that PGF2 alpha and PMA stimulate progesterone production and that PGF2 alpha increases the intracellular free calcium and inositol phosphates of human cultured luteal cells in the mid-luteal phase. PMID- 1613448 TI - Localization of androgen receptors in human skin by immunohistochemistry: implications for the hormonal regulation of hair growth, sebaceous glands and sweat glands. AB - A mouse monoclonal antibody against the N-terminal region of human androgen receptor (AR) was used to identify receptors by immunoperoxidase staining in frozen serial sections of skin from scalp, face, limb and genitalia of men and women aged 30-80 years. AR staining was restricted to cell nuclei. In sebaceous glands, AR were identified in basal and differentiating sebocytes. The percentage of receptor-positive basal sebocyte nuclei in the temple/forehead region was greater in males (65%) than in females (29%). AR staining was restricted to the cells of dermal papillae in anagen and telogen hair follicles. The percentage of dermal papillae containing AR was greater in males (58%) than in females (20%). The number of positively stained dermal papillae was lowest in female scalp skin. In 163 hair follicles sectioned, AR were absent from germinative matrix, outer root sheath (including the bulge region), inner root sheath, hair shaft and hair bulb, and from the capillaries present in some large dermal papillae. AR were present in pilosebaceous duct keratinocytes, suggesting that androgens may influence pilosebaceous duct keratinization. AR were also identified in interfollicular epidermal keratinocytes and dermal fibroblasts although, in both cell types, intensity and frequency of staining were greatest in genital skin. AR were identified in luminal epithelial cells of apocrine glands in genital skin and in certain cells of the secretory coils of eccrine sweat glands in all body sites. This study indicates that androgens regulate sebaceous gland and hair growth by acting upon two different types of target cells, the epithelial sebocytes of sebaceous glands and the mesenchymal cells of the hair follicle dermal papilla.(ABSTRACT TRUNCATED AT 250 WORDS) PMID- 1613449 TI - Uptake of L-tri-iodothyronine by human cultured trophoblast cells. AB - We investigated the uptake of L-tri-iodothyronine (T3) by cultured human trophoblast cells. Uptake was time-dependent, initially linear and approaching equilibrium after 60 min with an approximate half-time of 13 +/- 4.5 min (mean +/ S.E.M., n = 4). It had a non-saturable component accounting for about 50% of total uptake. We demonstrated a single saturable T3 uptake mechanism with a calculated Michaelis constant (Km) of 755 +/- 145 nmol/l (n = 11-13) and a corresponding maximum velocity of 28.8 +/- 5.3 pmol/min per mg protein (n = 11 13). The Km value was similar to those reported in other tissues. PMID- 1613450 TI - Developmental changes in memorial comparisons: the effects of stimulus presentation mode. AB - First graders, fifth graders, and college students made comparative size judgments of either pictures (line drawings) or names (spoken words) of common objects by designating the "bigger" item in real life. Care was taken to equate the picture and word conditions on a number of critical parameters including method of item-pair presentation and activation of response-time intervals. All groups exhibited a symbolic distance effect. While judgments were faster with pictures than words, the magnitude of the difference did not change with age. Previous research suggesting a marked developmental decline in the magnitude of the "pictorial superiority effect" may have confounded reduced memory demands with stimulus presentation mode for young children. Finally, slopes of the symbolic distance functions were found to decrease with increasing grade level, at least from first to fifth grade. This is the first demonstration of an age related decline in slopes for magnitude comparisons of concrete objects. PMID- 1613451 TI - Intention and outcome: key components of causal structure facilitating mapping in children's analogical transfer. AB - The consequences of two key features of causal structure in source stories, intention and positive outcome, for analogical transfer were examined in kindergarten and second graders. In Experiment 1, children received either structure-complete, structure-incomplete, or irrelevant source stories. Structure incomplete stories lacked either the intention to solve a problem (a goal directed component), evidence of a successful consequence (an outcome-related component), or both as part of the solution activity described in source stories. Evidence for transfer was obtained for second graders when a goal-directed component, and to a lesser extent, an outcome-related component were connected to the solution action in source stories. Differences among conditions for kindergartners were less evident, although they revealed a pattern of performance similar to the second graders. A second experiment was conducted to determine whether memory and an orientation to use the source story information might account for these findings. Efforts to ensure memory for and hints to use information in the source stories, however, did not benefit solution transfer when intention and positive outcome were absent. These results suggest that a complete causal structure, including goal and outcome, in source stories augments transfer in young children by promoting mapping of the analogical relationship between source stories and the target problem. PMID- 1613452 TI - Conservation acquisition, maintenance, and generalization by mentally retarded children using equality-rule training. AB - To teach conservation to mildly retarded, preoperational preadolescents (9 to 12 years old), a number-representational system was used to mediate the invariance of quantity as part of "equality-rule" training. Before viewing a perceptually misleading configuration of either two equal quantities or two unequal quantities entailing the dimensions of number or length, participants learned that equality involved the assignment of two identical numbers and inequality the assignment of two different numbers. These numbers were then applied to the actual quantities and became the basis for rule statements that were rehearsed, memorized, and subject-generated each time the quantities were transformed into a new configuration. Following equality training, correct judgments and verbal justifications of conservation were high (M greater than or equal to 85%) during both immediate and delayed post-tests and for near-generalization (number and length) and far-generalization (weight, liquid substance, and solid substance) tasks. In contrast, the post-test levels of comparable participants given learning-set (LS) training, LS plus verbal-rule training (a combination of statements about identity, negation, and compensation), or no training at all were substantially and significantly lower. Equality training is of theoretical and practical interest because of its potential to teach a symbolic representational rule that directly and meaningfully articulates the quantitative properties of objects and counteracts the overreliance on task-specific and faulty perceptual cues inherent in the conservation task. PMID- 1613453 TI - Manipulation of visual mental images in children and adults. AB - Recently, there has been a debate on whether visual patterns can be transformed and reinterpreted in mental imagery. In the present study, task demands and age of subjects were manipulated to see whether children and adults were able to discover a novel visual pattern after transforming a mental image. Two tasks, called combination and subtraction, were devised. They consist of either compounding or taking away parts of images to discover a new construal. Results indicate that not only adults, but also children aged 6 and 10, are able to transform a mental image so as to yield another image with a different interpretation. Task demands had a greater effect on children than adults, consistent with the suggestion that the ease of manipulating mental images is a function of the efficiency of control processes. PMID- 1613455 TI - Developmentally regulated association of a 56-kD member of the surface immunoglobulin M receptor complex. AB - Immature and mature B cells differ in the signals generated and transduced through their antigen receptor, surface immunoglobulin M (sIgM). Whereas signals generated through sIgM on mature B cells initiate a program leading to the positive activation of these cells, signaling through this receptor at the immature stage of development leads to a state of induced unresponsiveness or tolerance. Our previous studies have described developmental differences in sIgM transmembrane signaling that are independent of ligand-receptor affinity. In an attempt to understand the molecular basis for signaling differences between immature and mature B cells, we have analyzed the sIgM receptor complex in neonatal and adult mouse splenic B cells. While previously described components of this complex do not exhibit marked developmentally regulated differences in their association with sIgM, we have identified a 56-kD protein that associates with sIgM in mature (antigen-responsive), but not immature (tolerance-sensitive) B cells. This protein (p56) associates with sIgM as a homodimer, is constitutively phosphorylated on tyrosine, and is coimmunoprecipitated with IgM but not IgD. The observed inability to iodinate p56 suggests it is an intracellular component of the receptor complex. Based upon its migration in one- and two-dimensional gel electrophoresis we show, however, that p56 is distinct from the blk, lyn, or fyn src family kinases that have been shown to be associated with sIgM in mature B cells. The developmentally regulated participation of p56 in the B cell antigen receptor complex suggests a role in the differential signaling mediated via sIgM on immature and mature B cells. PMID- 1613454 TI - Measles virus transmembrane fusion protein synthesized de novo or presented in immunostimulating complexes is endogenously processed for HLA class I- and class II-restricted cytotoxic T cell recognition. AB - The routes used by antigen-presenting cells (APC) to convert the transmembrane fusion glycoprotein (F) of measles virus (MV) to HLA class I and class II presentable peptides have been examined, using cloned cytotoxic T lymphocytes in functional assays. Presentation by Epstein-Barr virus-transformed B lymphoblastoid cell lines was achieved using live virus, ultraviolet light inactivated virus, and purified MV-F delivered either as such or incorporated in immunostimulating complexes (MV-F-ISCOM). Only live virus and MV-F-ISCOM allow presentation by class I molecules, while all antigen preparations permit class II restricted presentation. We observe presentation of MV-F from live virus and as MV-F-ISCOM by class II molecules in a fashion that is not perturbed by chloroquine. Our studies visualize novel presentation pathways of type I transmembrane proteins. PMID- 1613456 TI - Peptide-induced stabilization and intracellular localization of empty HLA class I complexes. AB - The human cell line T2 has been reported to be class I assembly deficient, and accordingly expresses reduced amounts of HLA-A2 and no HLA-B5 at the cell surface. By immunoblotting we observe the steady-state class I heavy chain levels of T2 to be near normal when compared with the identical class I alleles of the wild-type cell line T1. In pulse chase experiments, formation of heavy chain beta 2-microglobulin complexes is observed for both HLA-A2 and HLA-B5. Culture at reduced temperatures (26 or 20 degrees C) does not increase the amount of class I molecules transported, unlike what has been reported for the class I assembly deficient mouse mutant cell line RMA-S. The HLA-B5 and the HLA-A2 complexes formed by T2 are thermolabile in cell lysates, albeit to different degrees. The thermolability of HLA-B5 can be overcome by addition of HLA-B5-presentable peptides, obtained by trifluoroacetic acid extraction from an HLA-B5-positive cell line, underlining the necessity of peptide for class I stability and indicating that T2-derived class I complexes are devoid of peptide. Cytoplast fusion of T2 cells with RMA-S cells shows the defect in class I assembly of RMA-S to be similar to that of T2. Localization of class I molecules observed by immuno electron microscopy reveals the accumulation in the T2 cell line of both HLA-B5 and HLA-A2 in the endoplasmic reticulum (ER). Class I molecules are present in all the cisternae of the Golgi complex of T2, but the ratio of HLA-A and -B locus products in the Golgi area differs significantly from that at the cell surface. We conclude that the requirement for peptide in transport of class I molecules manifests itself at a stage beyond the ER, most likely the Golgi area. PMID- 1613457 TI - Analysis of a T cell receptor gene as a target of the somatic hypermutation mechanism. AB - In an effort to identify cis-acting elements required for targeting of the somatic hypermutation process in mice, we examined whether a T cell receptor (TCR) transgene under the control of the immunoglobulin (Ig) heavy (H) chain intron enhancer would be mutated in antigen-stimulated B cells. Hybridomas were established from splenic B cells of mice carrying two copies of the TCR transgene after hyperimmunization with phosphorylcholine keyhole limpet hemocyanin. Northern analysis revealed that all of the transgene-containing hybridomas expressed the TCR mRNA. Multiple somatic point mutations were found in seven of eight endogenous Ig VH genes examined. In contrast, 29 of 32 TCR genes examined contained no mutations. One potential mutation was seen in each of the three other TCR genes. Our data indicate that although the TCR transgene is expressed in B cells, it is not efficiently targeted by the mutator mechanism. Furthermore, the presence of an Ig H chain enhancer is itself not sufficient for targeting of the somatic hypermutation mechanism. PMID- 1613458 TI - Two unusual forms of human immunoglobulin E encoded by alternative RNA splicing of epsilon heavy chain membrane exons. AB - We present evidence for RNA transcripts encoding two forms of human epsilon immunoglobulin (Ig) heavy chain that differ significantly from those of other isotypes. We previously demonstrated three human epsilon mRNA species, instead of the two, corresponding to membrane and secreted proteins, seen with other heavy chain transcripts. In human genomic DNA downstream of the C epsilon gene, we identified sequences homologous to the two putative murine exons M1 (encoding a hydrophobic, presumably transmembrane region) and M2 (encoding hydrophilic residues). To determine the structures of epsilon transcripts containing these sequences, we amplified epsilon-related RNAs with the reverse transcriptase polymerase chain reaction. RNA was examined from fresh human B cells stimulated to IgE production by interleukin 4 plus anti-CD40, as well as from the human IgE producing line AF10. Instead of the single CH4-M1-M2 splice product predicted for murine membrane IgE, we found two other RNA species. One form has the structure CH4-M1'-M2, in which M1' includes the human sequence homologous to the murine M1 as well as a unique segment of 52 codons further upstream in the genomic sequence; this RNA species apparently encodes the IgE expressed on the membrane of IgE-producing lymphocytes. The other RNA has the structure CH4-M2', in which M2' is spliced in an alternative reading frame that includes an additional 109 codons downstream of the termination codon of the CH4-M1'-M2 form. Because the CH4-M2' mRNA form does not encode a hydrophobic segment, its translated product should be secreted. A secreted epsilon protein of approximately the size predicted for this form was identified by Western blotting. This novel IgE protein could play a significant and distinctive role in allergic disorders. PMID- 1613459 TI - Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system. AB - Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium. PMID- 1613460 TI - Transforming growth factor beta 2 inhibits cerebrovascular changes and brain edema formation in the tumor necrosis factor alpha-independent early phase of experimental pneumococcal meningitis. AB - Macrophages and granulocytes seem to play a key role in the pathogenesis of bacterial meningitis. Transforming growth factor beta (TGF-beta) leads to macrophage deactivation, as well as to inhibition of cytokine production and of endothelial granulocyte adhesion. We have investigated the influence of TGF-beta on regional cerebral blood flow (rCBF), intracranial pressure (ICP), and brain edema formation during the early phase of experimental meningitis. Rats which were inoculated intracisternally with live pneumococci or with pneumococcal cell wall hydrolyzed by the M1 muramidase (PCW-M) developed an increase of rCBF and ICP within 4 h postintracisternal challenge. A single intraperitoneal injection of TGF-beta 2 but not of TGF-beta 2 vehicle-control prevented the changes of rCBF. Furthermore, TGF-beta 2 significantly reduced the increase of ICP in rats inoculated with PCW-M. Likewise, the elevation of brain water content after intracisternal injection of pneumococci or PCW-M was blocked by pretreatment of rats with TGF-beta 2. TGF-beta 1 exhibited similar inhibitory effects in PCW-M injected rats. The beneficial effects of TGF-beta 2 on the initial phase after pneumococcal inoculation seem to be tumor necrosis factor alpha- (TNF-alpha) independent since (a) intracisternal or intraperitoneal injection of neutralizing anti-TNF-alpha antibodies did not significantly influence rCBF, ICP, and brain water content in PCW-M-induced meningitis; and (b) TNF-alpha was only occasionally detected at low levels in cerebrospinal fluid at 4 h after PCW-M application. PMID- 1613461 TI - Functional assembly of intrinsic coagulation proteases on monocytes and platelets. Comparison between cofactor activities induced by thrombin and factor Xa. AB - Generation of coagulation factor Xa by the intrinsic pathway protease complex is essential for normal activation of the coagulation cascade in vivo. Monocytes and platelets provide membrane sites for assembly of components of this protease complex, factors IXa and VIII. Under biologically relevant conditions, expression of functional activity by this complex is associated with activation of factor VIII to VIIIa. In the present studies, autocatalytic regulatory pathways operating on monocyte and platelet membranes were investigated by comparing the cofactor function of thrombin-activated factor VIII to that of factor Xa activated factor VIII. Reciprocal functional titrations with purified human factor VIII and factor IXa were performed at fixed concentrations of human monocytes, CaCl2, factor X, and either factor IXa or factor VIII. Factor VIII was preactivated with either thrombin or factor Xa, and reactions were initiated by addition of factor X. Rates of factor X activation were measured using chromogenic substrate specific for factor Xa. The K1/2 values, i.e., concentration of factor VIIIa at which rates were half maximal, were 0.96 nM with thrombin-activated factor VIII and 1.1 nM with factor Xa-activated factor VIII. These values are close to factor VIII concentration in plasma. The Vsat, i.e., rates at saturating concentrations of factor VIII, were 33.3 and 13.6 nM factor Xa/min, respectively. The K1/2 and Vsat values obtained in titrations with factor IXa were not significantly different from those obtained with factor VIII. In titrations with factor X, the values of Michaelis-Menten coefficients (Km) were 31.7 nM with thrombin-activated factor VIII, and 14.2 nM with factor Xa-activated factor VIII. Maximal rates were 23.4 and 4.9 nM factor Xa/min, respectively. The apparent catalytic efficiency was similar with either form of factor VIIIa. Kinetic profiles obtained with platelets as a source of membrane were comparable to those obtained with monocytes. These kinetic profiles are consistent with a 1:1 stoichiometry for the functional interaction between cofactor and enzyme on the surface of monocytes and platelets. Taken together, these results indicate that autocatalytic pathways connecting the extrinsic, intrinsic, and common coagulation pathways can operate efficiently on the monocyte membrane. PMID- 1613462 TI - Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. AB - Expression of the macrophage mannose receptor is inhibited by interferon gamma (IFN-gamma), a T helper type 1 (Th-1)-derived lymphokine. Interleukin 4 (IL-4), a Th-2 lymphocyte product, upregulates major histocompatibility class II antigen expression but inhibits inflammatory cytokine production by macrophages. We have studied the effect of IL-4 on expression of the macrophage mannose receptor (MMR) by elicited peritoneal macrophages. We found that recombinant murine IL-4 enhances MMR surface expression (10-fold) and activity (15-fold), as measured by the respective binding and degradation of 125I-mannose-bovine serum albumin. Polymerase chain reaction analysis of cDNAs from purified primary macrophage populations revealed that MMR, but not lysozyme or tumor necrosis factor alpha, mRNA levels were markedly increased by IL-4. The above effects were associated with morphologic changes. These data establish IL-4 as a potent and selective enhancer of murine MMR activity in vitro. IL-4 induces inflammatory macrophages to adopt an alternative activation phenotype, distinct from that induced by IFN gamma, characterized by a high capacity for endocytic clearance of mannosylated ligands, enhanced (albeit restricted) MHC class II antigen expression, and reduced proinflammatory cytokine secretion. PMID- 1613463 TI - Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype. PMID- 1613464 TI - Cyclosporin A markedly enhances superantigen-induced peripheral T cell deletion and inhibits anergy induction. AB - Cyclosporin A (CsA) is a well-known immunosuppressive agent that modulates immune tolerance in many ways. CsA can give rise to a state of long-term nonimmunosuppressed transplantation tolerance, but it can also aggravate autoimmune diseases, and provoke specific forms of autoimmunity. These effects, which are often paradoxical, remain largely unexplained. In this study, we investigated the effects of CsA on superantigen (superAg)-reactive peripheral T cells. The intravenous injection of either staphylococcal enterotoxin B (SEB), or Mls-1a cells into Mls-1b recipients, causes long-term in vitro nonresponsiveness (anergy) and partial elimination of the peripheral T cell receptor (TCR) V beta 8+/CD4+ and -V beta 6+/CD4+ T cell subsets, respectively. We report that CsA markedly enhances the peripheral elimination of SEB- and Mls-1a-reactive T cells such that up to 90% of the targeted CD4+/V beta subpopulations are deleted. The degree of deletion depends on the dose and the schedule of CsA administration, and the number of superAg injections. In situations where the extent of deletion is only moderate, we find that the remaining superAg-reactive T cells fail to develop anergy, unlike the T cells of control superAg-immunized mice. Higher doses of CsA are required to enhance T cell deletion (greater than or equal to 25 mg/kg/d, i.p.) than to impair anergy induction (greater than or equal to 6.25 mg/kg/d, i.p.). In view of these results, it appears that the degree of tolerance in CsA/superAg-treated mice depends on the balance between these opposing effects, i.e., enhancement of peripheral elimination versus the abrogation of anergy. The possibility of enhancing or preventing immune tolerance with a drug may have important clinical implications. PMID- 1613465 TI - The surface phenotype of dendritic cells purified from mouse thymus and spleen: investigation of the CD8 expression by a subpopulation of dendritic cells. AB - A new procedure for rapid isolation of dendritic cells (DC) was devised, involving collagenase digestion of tissues, dissociation of lymphoid-DC complexes, selection of light-density cells, then depletion of lymphocytes and other non-DC by treatment with a mixture of lineage-specific monoclonal antibodies (mAbs) and removal with anti-immunoglobulin-coupled magnetic beads. This enriched population (approximately 80% DC) was further purified when required by fluorescence-activated cell sorting for cells expressing high levels of class II major histocompatibility complex (MHC). The isolated DC were characterized by immunofluorescent staining using a panel of 30 mAbs. Thymic DC were surface positive for a number of markers characteristic of T cells, but they were distinct from T-lineage cells in expressing high levels of class II MHC, in lacking expression of the T cell receptor (TCR)-CD3 complex, and having TCR beta and gamma genes in germline state. Splenic DC shared many markers with thymic DC, but were negative for most T cell markers, with the exception of CD8. A substantial proportion of DC from both thymus and spleen expressed CD8 at high levels, comparable with that on T cells. This appeared to be authentic CD8, and was produced by the DC themselves, since they contained CD8 alpha mRNA. Thymic DC presented both the CD8 alpha and beta chains on the cell surface (Ly-2+3+), although the alpha chain was in excess; the splenic DC expressed only the CD8 alpha chain (Ly-2+3-). It is suggested that the expression of CD8 could endow certain antigen-presenting DC with a veto function. PMID- 1613466 TI - Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. AB - Cytokine-stimulated human osteosarcoma cells (MG-63) secrete several related chemotactic factors, including the neutrophil-activating protein interleukin 8 (IL-8) and the monocyte chemotactic protein (MCP)-1. We describe the isolation and characterization of two novel monocyte chemotactic factors from this tumor cell line. Although these proteins copurified with MCP-1 and IL-8 on heparin Sepharose, they could be separated by cation-exchange fast protein liquid chromatography and reverse-phase high-performance liquid chromatography. The corresponding 7.5- and 11-kD proteins were NH2-terminally blocked but were identified by sequencing peptide fragments. They showed a primary structure mostly related to that of MCP-1 and were therefore designated MCP-2 and MCP-3, respectively. These molecules can be classified in a subfamily of proinflammatory proteins characterized by the conservation of cysteine residues. MCP-2 and MCP-3 are also functionally related to MCP-1 because they specifically attract monocytes, but not neutrophils, in vitro. The chemotactic potency (specific activity) was comparable for all three MCPs. Intradermal injection of these proteins in rabbits resulted in selective monocyte recruitment in vivo. Since tumor cells are good producers of leukocyte chemotactic factors, it could be questioned whether these molecules can indirectly control tumor growth by attracting leukocytes or whether they rather promote invasion by the secretion of proteases from the attracted cells. PMID- 1613467 TI - Autoimmune syndromes in major histocompatibility complex (MHC) congenic strains of nonobese diabetic (NOD) mice. The NOD MHC is dominant for insulitis and cyclophosphamide-induced diabetes. AB - The development of autoimmune diabetes in the nonobese diabetic (NOD) mouse is controlled by multiple genes. At least one diabetogenic gene is linked to the major histocompatibility complex (MHC) of the NOD and is most likely represented by the two genes encoding the alpha and beta chains of the unique NOD class II molecule. Three other diabetogenic loci have recently been identified in the NOD mouse and are located on chromosomes 1, 3, and 11. In addition to the autoimmune diabetes which is caused by destruction of the insulin-producing beta cells in the pancreas, other manifestations of autoimmunity are seen in the NOD mouse. These include mononuclear cell inflammation of the submandibular and lacrimal glands, as well as the presence of circulating autoantibodies. To determine the effect of the non-MHC diabetogenic genes on the development of autoimmunity, we constructed the NOD.B10-H-2b (NOD.H-2b) strain, which possesses the non-MHC diabetogenic genes from the NOD mouse, but derives its MHC from the C57BL/10 (B10) strain. The NOD.H-2b strain does not develop insulitis, cyclophosphamide induced diabetes, or spontaneous diabetes. It does, however, develop extensive lymphocytic infiltrates in the pancreas and the submandibular glands that are primarily composed of Thy 1.2+ T cells and B220+ B cells. In addition, autoantibodies are present in NOD.H-2b mice which recognize the "polar antigen" on the insulin-secreting rat tumor line RINm38. These observations demonstrate that the non-MHC genes in the NOD strain, in the absence of the NOD MHC, significantly contribute to the development of autoimmunity. The contribution of a single dose of the NOD MHC to autoimmunity was assessed with a (NOD x NOD.H 2b)F1 cross. Although only approximately 3% of F1 females developed spontaneous diabetes, approximately 50% of both female and male F1 mice developed insulitis, and 25% of females and 17% of males became diabetic after treatment with cyclophosphamide. These data demonstrate that the MHC-linked diabetogenic genes of the NOD mouse are dominant with decreasing levels of penetrance for the following phenotypes: insulitis greater than cyclophosphamide-induced diabetes greater than spontaneous diabetes. PMID- 1613469 TI - Qualitative research. PMID- 1613468 TI - Requirement for CD8-major histocompatibility complex class I interaction in positive and negative selection of developing T cells. AB - The interaction of the T cell surface glycoprotein CD8 with major histocompatibility complex (MHC) class I molecules on target cells is required for effective T cell activation. Mutations in the alpha 3 domain of the MHC class I molecule can disrupt binding to CD8, yet leave antigen presentation unaffected. Here we show that such a mutation can interfere with positive and negative selection of T cells bearing T cell receptors (TCRs) that interact specifically with the mutant class I molecule. Autoreactive T cells in male mice expressing a transgenic TCR specific for the male antigen H-Y and H-2Db were not deleted in the context of a transgenic Db molecule bearing a mutation at residue 227. Similarly, CD8+ cells were not positively selected in female mice expressing both the TCR and mutant class I transgenes. Endogenous MHC class I molecules were competent to bind CD8, but were unable to rescue the defect, indicating a requirement for coordinate recognition of antigen/MHC by a complex of the TCR and CD8 coreceptor for both positive and negative selection of thymocytes. PMID- 1613470 TI - Ultrasound screening in pregnancy. PMID- 1613471 TI - Referral and consultation in primary care: do we understand what we're doing? PMID- 1613472 TI - Parenting vs patient care. PMID- 1613473 TI - Maternity leave for practicing family physicians. AB - BACKGROUND: Approximately 37% of all medical students and 36% of family medicine residents in training in the United States are women. The American Academy of Family Physicians (AAFP) has developed a recommended parental leave policy for residents in training but has not established a similar policy for physicians in practice. The purpose of this study was to assess the prevalence of maternity leave policies for practicing family physicians. METHODS: A 14-item self administered survey questionnaire was designed and mailed to 940 AAFP members randomly selected from the total active female membership. RESULTS: A 52% response rate was obtained. The mean age of respondents was 35 years. Only one third of the physicians not in solo practice reported having a stated maternity leave policy in their current place of practice. Academic programs, when compared with single specialty family practice groups, multispecialty groups and health maintenance organization (HMO) or preferred provider organization (PPO) groups, were more likely to have maternity leave policies and to provide salary on leave. Practice groups with eight or more partners were more likely to have policies that provided salary and benefits while on leave. Ninety percent of respondents requested maternity leave guidelines for practicing family physicians. CONCLUSIONS: Women family physicians expressed strong interest in the development of maternity leave guidelines for their specialty. Guideline components are outlined. PMID- 1613474 TI - Patients presenting to family physicians after a fall: a report from the Ambulatory Sentinel Practice Network. AB - BACKGROUND: Patients who fall present a diagnostic challenge to family physicians. The diagnostic workup of these patients must be thorough enough to detect and treat important causes of the fall yet not subject patients to unnecessary tests. Previous studies have provided only limited guidance for primary care physicians because in general they occurred in settings other than primary care and focused on a single age group. METHODS: The Ambulatory Sentinel Practice Network (ASPN) conducted a 6-month study of primary care patients of all ages presenting after a fall, or with medical problems resulting from a fall. ASPN clinicians collected information about the history, physical examination findings, and follow-up of these patients. Causes of falls were grouped into three categories: external reasons for falling, internal reasons related to gait, and internal reasons unrelated to gait. RESULTS: Participating clinicians identified 431 patients who had falls out of the 256,680 seen for any reason during the study period. The patients ranged in age from 1 to 94 years. The rate of falls for patients increased rapidly after age 65 years. Most falls occurred for reasons external to the patient, but internal reasons, both nonlocomotor and locomotor, increased after age 65 years. No nonlocomotor causes for a fall were found in patients younger than 65 years of age. Also, the rate of hospitalization of patients seen for falls was greater in the geriatric age group. CONCLUSIONS: The results highlight the need for further research about falls, particularly those occurring in pediatric and young adult patients. Furthermore, correcting environmental hazards and modifying gait problems in the elderly by increasing lower extremity and truncal strength could decrease the risk of falling. PMID- 1613475 TI - Giardia antigen detection in patients with chronic gastrointestinal disturbances. AB - BACKGROUND: Giardia lamblia, a protozoan parasite, is transmitted by cysts in contaminated water or food or by person-to-person contact. The standard in diagnosis has been the microscopic demonstration of fecal cysts, which yields many false negatives due to high variability in cyst excretion. A new method that detects infection even when few parasites are present is now available. This immunodiagnostic test is rapid, sensitive, and specific, and typically requires only a single stool specimen. In this study patients with gastrointestinal (GI) complaints were screened for Giardia antigens, and the test results were compared to conventional microscopy. Costs incurred by patients with chronic GI problems were documented. METHODS: Twelve patients with GI complaints were tested for Giardia by microscopy and 13 patients by the immunodiagnostic test. Patient charts were evaluated for pertinent history and the diagnostic tests ordered before giardiasis was considered. RESULTS: For all patients, microscopy was uniformly negative, but 6 of 13 patients were antigen positive. Patients with chronic complaints, later found to test positive for Giardia, typically underwent five diagnostic tests at a cost of $338. CONCLUSIONS: Giardiasis, an increasing problem in family practice, should be considered early in patients with GI disturbances. New, sensitive immunodiagnostic tests that usually require a single specimen are more useful than microscopy. Prompt diagnosis of giardiasis not only relieves patients of unpleasant symptoms, but can avoid unnecessary and costly evaluations. PMID- 1613476 TI - The association of parental alcoholism and rigidity with chronic illness and abuse among women. AB - BACKGROUND: This study determined whether women in a primary care practice who described one or both of their parents as alcohol dependent (group A) or harsh, rigid, or difficult (group B) were more likely to have chronic illness than women who denied having parents with these characteristics (group C). METHODS: A consecutive sample of 120 women scheduled for comprehensive physical examinations were interviewed to determine parental characteristics, demographic data (age, education, employment, and marital status), and clinical information (chronic illness and lifetime surgeries). In addition, all women were asked standardized questions about sexual and physical abuse. RESULTS: The overall difference among the groups for women with a history of chronic illness was significant (P less than .001). More women in groups A (55%) and B (48%) were identified with chronic illness than in group C (18%). Women in groups A and B also reported more sexual and physical abuse (32% and 44%, respectively) than women in group C (8% [P less than .001]). Women identifying abuse were diagnosed with more chronic illness (67%, compared with 25% [P less than .001]) and more lifetime surgeries (3.3 compared with 1.75 [P less than .05]) than women denying abuse. CONCLUSIONS: Parental alcoholism and parental rigidity were associated with increased prevalence of chronic illness and physical or sexual abuse among women patients. PMID- 1613477 TI - Home assessment of adherence to long-term medication in the elderly. AB - BACKGROUND: Drug nonadherence to long-term medication is a common and poorly understood problem in the elderly. A study was conducted to assess whether elderly patients would accept a research assistant conducting pill counts in their homes, and to examine how nonadherence was associated with patient variables. METHODS: A letter and a telephone follow-up call were used to identify eligible patients (aged 65 years and over, with two or more chronic diseases). RESULTS: A total of 98 eligible patients were identified. Fifty-nine agreed to participate in the study. Of the 59 participants, 54.7% were nonadherent to their medication regimen. Nonadherence was defined as an overall mean level of compliance of less than 80%. Drug regimen nonadherence was associated with the inability to read medication labels (P less than .01), but not with impaired visual acuity, the number of prescribed medications, the type of medication container lid, depression, cognitive impairment, perceived health status, or the cost of medications. Frequency of drug administration affected patient adherence to the medication regimen. Mean adherence of patients to prescriptions for drugs to be taken once or twice daily was 72%, whereas drugs to be taken three or four times daily had a mean adherence rate of 54% (P less than .01). CONCLUSIONS: Using the simple pill count method on home visits, rates of nonadherence to long term medication were comparable to those found in studies using electronic pill counting devices. Larger studies are needed to clarify how other variables, in addition to patient inability to read medication labels, are associated with noncompliance with medication regimens for chronic diseases in elderly patients. PMID- 1613478 TI - A critical assessment of preterm labor prevention strategies. AB - Preterm birth is second only to congenital diseases in causing morbidity and mortality in infants. To prevent preterm labor and delivery, a number of strategies have been developed. When choosing a strategy to prevent preterm birth, however, physicians must remember that preterm delivery arises from three separate conditions: iatrogenic preterm labor, premature rupture of membranes, and idiopathic preterm labor. Many of the programs that have been developed focus on patients who are at high risk for iatrogenic preterm birth and premature rupture of membranes, but do not include patients who are likely to experience idiopathic preterm labor. Since idiopathic preterm labor is the most common cause of preterm birth and is the most amenable to early intervention with tocolytic agents, more preterm labor education efforts should be included in prenatal care programs. In addition, further research is needed to delineate which features of preterm birth prevention programs are responsible for the beneficial effects that have been observed. PMID- 1613480 TI - The Bethesda System for reporting cervical and vaginal cytologic diagnoses: report of the 1991 Bethesda workshop. PMID- 1613479 TI - Calcitonin in the treatment of osteoporotic bone pain. AB - Calcitonin has been observed to have an analgesic effect on painful bone conditions. A case illustrating the antinociceptive effect of calcitonin on bone pain caused by osteoporotic vertebral compression fracture is presented. There is increasing clinical evidence supporting this phenomenon, though few rigorously controlled studies exist. Calcitonin may have an advantage over other analgesics in the treatment of bone pain resulting from an osteoporotic compression fracture, because, in addition to the observed analgesic effect, it is useful in treating the underlying disorder. PMID- 1613481 TI - Fusion of membranes during fertilization. Increases of the sea urchin egg's membrane capacitance and membrane conductance at the site of contact with the sperm. AB - The early events of fertilization that precede and cause activation of an egg have not been fully elucidated. The earliest electrophysiological change in the sea urchin egg is a sperm-evoked increase of the egg's membrane conductance. The resulting depolarization facilitates entry of the fertilizing sperm and precludes the entry of supernumerary sperm. The sequence of the increase in the egg's membrane conductance, gamete membrane fusion, egg activation, and sperm entry, including causal relationships between these events, are not known. This study reports the use of whole egg voltage clamp and loose patch clamp to monitor simultaneously changes of membrane conductance and capacitance at the site of sperm-egg contact. Measurements were made during sperm-egg interactions where sperm entry readily proceeded or was precluded by maintaining the egg's membrane potential either at large, negative values or at positive values. Whenever the sperm evoked an increase of the egg's membrane conductance, that increase initiated abruptly, was localized to the site of sperm attachment, and was accompanied by a simultaneous abrupt increase of the membrane capacitance. This increase of capacitance indicated the establishment of electrical continuity between gametes (possibly fusion of the gametes' plasma membranes). If sperm entry was blocked by large negative membrane potentials, the capacitance cut off rapidly and simultaneously with a decrease of the membrane conductance, indicating that electrical continuity between gametes was disrupted. When sperm entry was precluded by positive membrane potentials, neither conductance nor capacitance increased, indicating that sperm entry was halted before the fusion of membranes. A second, smooth increase of capacitance was associated with the exocytosis of cortical granules near the sperm in eggs that were activated. Electrical continuity between the gametes always preceded activation of the egg, but transient electrical continuity between the gametes alone was not always sufficient to induce activation. PMID- 1613482 TI - Oxygen distribution and consumption in the cat retina during normoxia and hypoxemia. AB - Oxygen tension (PO2) was measured with microelectrodes within the retina of anesthetized cats during normoxia and hypoxemia (i.e., systemic hypoxia), and photoreceptor oxygen consumption was determined by fitting PO2 measurements to a model of steady-state oxygen diffusion and consumption. Choroidal PO2 fell linearly during hypoxemia, about 0.64 mmHg/mmHg decrease in arterial PO2 (PaO2). The choroidal circulation provided approximately 91% of the photoreceptors' oxygen supply under dark-adapted conditions during both normoxia and hypoxemia. In light adaptation the choroid supplied all of the oxygen during normoxia, but at PaO2's less than 60 mmHg the retinal circulation supplied approximately 10% of the oxygen. In the dark-adapted retina the decrease in choroidal PO2 caused a large decrease in photoreceptor oxygen consumption, from approximately 5.1 ml O2/100 g.min during normoxia to 2.6 ml O2/100 g.min at a PaO2 of 50 mmHg. When the retina was adapted to a rod saturating background, normoxic oxygen consumption was approximately 33% of the dark-adapted value, and hypoxemia caused almost no change in oxygen consumption. This difference in metabolic effects of hypoxemia in light and dark explains why the standing potential of the eye and retinal extracellular potassium concentration were previously found to be more affected by hypoxemia in darkness. Frequency histograms of intraretinal PO2 were used to characterize the oxygenation of the vascularized inner half of the retina, where the oxygen distribution is heterogeneous and simple diffusion models cannot be used. Inner retinal PO2 during normoxia was relatively low: 18 +/- 12 mmHg (mean and SD; n = 8,328 values from 36 profiles) in dark adaptation, and significantly lower, 13 +/- 6 mmHg (n = 4,349 values from 19 profiles) in light adaptation. Even in the dark-adapted retina, 30% of the values were less than 10 mmHg. The mean PO2 in the inner (i.e., proximal) half of the retina was well regulated during hypoxemia. In dark adaptation it was significantly reduced only at PaO2's less than 45 mmHg, and it was reduced less at these PaO2's in light adaptation. PMID- 1613483 TI - Hemisodium, a novel selective Na ionophore. Effect on normal human erythrocytes. AB - Hemisodium is a novel Na ionophore that belongs to the class of compounds called cryptands. These compounds possess an electron-rich cavity for binding of cations and are conformationally organized during synthesis to favor the selective binding of one cation over another. In media containing 145 mM NaCl and 5 mM KCl, hemisodium (10(-5) M) increased erythrocyte Na content from 23 to 345 mmol/kg.dry cell solid (dcs) over 4 h and increased water content from 1.8 to 3.5 liter/kg.dcs over the same period. K content decreased somewhat over the same time period, but this fall in K content was prevented entirely by incubation in either low Na media (to prevent net Na entry) or in Cl free media. Thus, the decrease in K content in high NaCl media was due to cell swelling, which activated KCl cotransport, and not due to a direct action of hemisodium on K permeability. Hemisodium-mediated Na transport was conductive, because erythrocyte membrane potential (Vm), determined by diS-C3-5 fluorescence, changed from -9 to +22 mV in high Na media in the presence of hemisodium and DIDS. In cells equilibrated with sulfamate, an anion with low conductive permeability, Vm changed 54 mV per 10-fold change in external Na concentration with the addition of hemisodium. In contrast, a 10-fold change in the external concentration of K, Rb, Cs, or T1 failed to alter Vm in the presence of hemisodium, suggesting a high Na specificity of the ionophore. Na conductance determined from net fluxes increased from 0.04 to 5.2 microS/cm2 with 10 microM hemisodium, and with that concentration the ratio of Na to K conductance was 45:1. Among the Na ionophores available so far, hemisodium appears to have the greatest specificity. Hemisodium may be a valuable tool in membrane transport studies. PMID- 1613484 TI - Mechanism of 4-aminopyridine action on voltage-gated potassium channels in lymphocytes. AB - The mechanism by which 4-aminopyridine (4-AP) blocks the delayed rectifier type potassium (K+) channels present on lipopolysaccharide-activated murine B lymphocytes was investigated using whole-cell and single channel patch-clamp recordings. 4-AP (1 microM-5 mM) was superfused for 3-4 min before applying depolarizing pulses to activate the channel. During the first pulse after application of 4-AP above 50 microM, the current inactivated faster, as compared with the control, but its peak was only reduced at high concentrations of 4-AP (Kd = 3.1 mM). During subsequent pulses, the peak current was decreased (Kd = 120 microM), but the inactivation rate was slower than in the control, a feature that could be explained by a slow unblocking process. After washing out the drug, the current elicited by the first voltage step was still markedly reduced, as compared with the control one, and displayed very slow activation and inactivation kinetics; this suggests that the K+ channels move from a blocked to an unblocked state slowly during the depolarizing pulse. These results show that 4-AP blocks K+ channels in their open state and that the drug remains trapped in the channel once it is closed. On the basis of the analysis of the current kinetics during unblocking, we suggest that two pathways lead from the blocked to the unblocked states. Computer simulations were used to investigate the mechanism of action of 4-AP. The simulations suggest that 4-AP must bind to both an open and a nonconducting state of the channel. It is postulated that the latter is either the inactivated channel or a site on closed channels only accessible to the drug once the cell has been depolarized. Using inside- and outside-out patch recordings, we found that 4-AP only blocks channels from the intracellular side of the membrane and acts by reducing the mean burst time. 4-AP is a weak base (pK = 9), and thus exists in ionized or nonionized form. Since the Kd of channel block depends on both internal and external pH, we suggest that 4-AP crosses the membrane in its nonionized form and acts from inside the cell in its ionized form. PMID- 1613486 TI - Orienting task effects on memory for presentation modality in children, young adults, and older adults. AB - Children (7 to 10 years), young adults (17 to 24 years), and older adults (55 to 77 years) were asked to learn three lists of words that were of mixed modality (half the words were visual, and half the words were auditory). With one list the subjects were asked a semantic orienting question; with another, a nonsemantic orienting question; and with a third, no orienting question. Half the subjects in each age group were also asked to remember the presentation modality of each word. Older adults remembered less information about modality than children and young adults did, and the variation in the type of orienting question--or the lack of one--affected modality identification. However, there was no Orienting Task x Age interaction for modality identification. The results of this study suggest that encoding modality information does not take place automatically--in any age group--but that explanations focusing on encoding strategies and effort are not likely to account for older adults' difficulties in remembering presentation modality. PMID- 1613488 TI - Using cerebral dominance for education programs. AB - Instructional methods in today's classroom are sometimes based on the notion of cerebral dominance. However, the link between hemispheric laterality and education practice is highly questionable. One instrument used by teachers to assess individual differences in cerebral dominance is a paper-and-pencil survey called Your Style of Learning and Thinking (SOLAT; Torrance, Reynolds, Riegel, & Ball, 1977). In this study, the authors explored the psychometric properties of the SOLAT in three phases. In the first phase, the authors examined SOLAT's construct validity. Contrary to cerebral dominance theory, a principal factor analysis revealed a seven-factor solution. The second phase was conducted to determine the SOLAT's internal consistency and test-retest reliability coefficients. As expected, these analyses generated low to moderate correlations. In the final phase, the authors further examined the SOLAT's construct validity by comparing the performance of brain-injured versus normal adults. With one exception, there were no significant differences. The results of this study did not support the notion of hemisphericity, at least not as measured by the SOLAT. Therefore, educators should not use the SOLAT to categorize students in terms of their preferred mode of processing information. PMID- 1613487 TI - Primary depth cues and background pattern in the portrayal of slant. AB - A rectangularity postulate has been used in algorithms for the purpose of interpreting two-dimensional representations of rectilinear objects. This rectangularity postulate may affect the perception of true surfaces. In this study, rectangular surfaces and trapezoidal surfaces--the latter simulating the horizontal slant-in-depth of the rectangular surfaces--were viewed under static monocular, moving-monocular, and static-binocular conditions, both with and without a background pattern. The static-binocular condition elicited the greatest number of accurate responses. The moving-monocular condition did not elicit significantly more accurate responses than the static-monocular viewing condition did. The effect of background pattern was insignificant. These results were unexpected in terms of ecological validity and (regarding moving-monocular viewing) because of the importance of the role of relative visual motion in the detection of object motion. However, the results are consistent with the perception of depth separation of two discrete objects. PMID- 1613485 TI - Electrophysiological effects of basolateral [Na+] in Necturus gallbladder epithelium. AB - In Necturus gallbladder epithelium, lowering serosal [Na+] ([Na+]s) reversibly hyperpolarized the basolateral cell membrane voltage (Vcs) and reduced the fractional resistance of the apical membrane (fRa). Previous results have suggested that there is no sizable basolateral Na+ conductance and that there are apical Ca(2+)-activated K+ channels. Here, we studied the mechanisms of the electrophysiological effects of lowering [Na+]s, in particular the possibility that an elevation in intracellular free [Ca2+] hyperpolarizes Vcs by increasing gK+. When [Na+]s was reduced from 100.5 to 10.5 mM (tetramethylammonium substitution), Vcs hyperpolarized from -68 +/- 2 to a peak value of -82 +/- 2 mV (P less than 0.001), and fRa decreased from 0.84 +/- 0.02 to 0.62 +/- 0.02 (P less than 0.001). Addition of 5 mM tetraethylammonium (TEA+) to the mucosal solution reduced both the hyperpolarization of Vcs and the change in fRa, whereas serosal addition of TEA+ had no effect. Ouabain (10(-4) M, serosal side) produced a small depolarization of Vcs and reduced the hyperpolarization upon lowering [Na+]s, without affecting the decrease in fRa. The effects of mucosal TEA+ and serosal ouabain were additive. Neither amiloride (10(-5) or 10(-3) M) nor tetrodotoxin (10(-6) M) had any effects on Vcs or fRa or on their responses to lowering [Na+]s, suggesting that basolateral Na+ channels do not contribute to the control membrane voltage or to the hyperpolarization upon lowering [Na+]s. The basolateral membrane depolarization upon elevating [K+]s was increased transiently during the hyperpolarization of Vcs upon lowering [Na+]s. Since cable analysis experiments show that basolateral membrane resistance increased, a decrease in basolateral Cl- conductance (gCl-) is the main cause of the increased K+ selectivity. Lowering [Na+]s increases intracellular free [Ca2+], which may be responsible for the increase in the apical membrane TEA(+)-sensitive gK+. We conclude that the decrease in fRa by lowering [Na+]s is mainly caused by an increase in intracellular free [Ca2+], which activates TEA(+)-sensitive maxi K+ channels at the apical membrane and decreases apical membrane resistance. The hyperpolarization of Vcs is due to increase in: (a) apical membrane gK+, (b) the contribution of the Na+ pump to Vcs, (c) basolateral membrane K+ selectivity (decreased gCl-), and (d) intraepithelial current flow brought about by a paracellular diffusion potential. PMID- 1613489 TI - Does memory contaminate test-retest reliability? AB - The Wonderlic Personnel Test (1983) was administered twice over a 3-week period under conditions in which the activity of the second test was experimentally manipulated. Data from 302 undergraduates were analyzed. The standard test-retest reliability coefficient, .872, was not significantly different from the coefficients obtained from three other groups that, on the second test, were each given specific instructions: (a) to reason out the answers (pure reassess condition); (b) to use reasoning, memory of their initial responses, or both (reassess and memory); or (c) to take an alternate form of the test (parallel). However, the standard test-retest reliability coefficient was higher, p less than .10, than the coefficient obtained from a condition (pure memory) in which subjects were instructed to duplicate their previous responses, using only memory. Although the subjects in the test-retest and combined reassess and memory conditions reported recalling previous answers for 20-25% of the items on the second test, it was concluded that conscious repetition of specific responses did not seriously inflate the estimate of test-retest reliability. PMID- 1613490 TI - Auditory imagery and free recall. AB - Research on mental imagery has demonstrated the importance of visual imagery to recall performance. Little attention, however, has been paid to the mnemonic value of auditory imagery. The present experiments addressed the influence of auditory and visual imagery on free recall. Characteristic sounds, pictures, or printed verbal labels of 40 common items were presented sequentially to adult subjects, who were asked to recall them after a 2-min retention interval. Pictures and characteristic sounds were associated with significantly better recall than were verbal labels alone, indicating that auditory imagery has mnemonic value similar to that of visual imagery. This effect was confirmed by further experiments. However, the effects of auditory and visual imagery on free recall were not shown to be additive.